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JOURNAL OF NEONATOLOGYVolume 31 / Issue I & II / January - June 2017

Contents1 Editors Page

Research Articles

2 Impact of Early CPAP on The Respiratory Care of 1

Preterm Babies- An Audit

Naveen Jain, Jemila James

3 High-Flow Nasal Cannula Versus CPAP for Respiratory 6

Support in Preterm Infants

Abdul Razak, Siddu Charki, N Karthik Nagesh

4 Pulse Oximetry as Screening Test for Early-onset Sepsis in 11

Newborns in Tertiary Hospitals in India

R. Swamy, A Razak, P. Mohanty

5 Causes and Predictors of Mortality in Newborns Referred 15

to Tertiary Level NICU

Ghanghoriya P, Agarwal G, Barman ML, Sudhir U

Noninvasive Ventilation in Newborns

6 High Flow Nasal Canula Therapy (HHHFNC) 22

in Neonates –Will it Replace CPAP?

Abdul Razak, N Karthik Nagesh

7 CPAP for Respiratory Distress in Newborns: 27

A Decade of Experience

Srinivas Murki, Hemasree Kandraju, Tejo Pratap Oleti, Anupama, Pramod Gaddam

8 NIPPV In The Neonate: Answers To FAQs – 31

A Personal Perspective

Vineet Bhandari

9 Non- Invasive Ventilation in Neonatal RDS – The Way to Go 35

N. Karthik Nagesh, Mrinal Pillai

10 Non-Invasive Ventilation and its Impact on Bronchopulmonary Dysplasia 38

Naveen Bajaj

Case Reports

11 Right Femur Fracture during Caesarean Delivery 44

Rajesh Rai, Shital Kolhe, Kapil Shukla

12 An Unusual Presentation of Neonatal Osteomyelitis as Erb’s 48

Palsy with an Unusual Causative Pathogen

Priyanka Gupta, Veena Devgan, Dalip Kumar Bhagwani, Monika Matlani

13 Spontaneous Umbilical Cord Hematoma; An Unusual 51

Clue for Early Onset Neonatal Sepsis

Priyanka Gupta, Abhinav Jain, Amlin Shukla, Ashok Kumar Patwari

Dear Friends ,

Greetings from National Neonatology Forum !!!!

stIt gives me immense pleasure that after all the teething problems the 1 issue of year 2017 is in your hands.

We were in process of giving a new look to journal. The contents have been rationalized. Dr.MohitSahni

has taken great pains as Guest Editor to enhance the academic contents. We the office bearers, governing

body members and journal committee members are committed to bring out journal regularly to the

satisfaction of our members. I am happy to share with you that NNF has entered into an agreement with

World Renowned Publishing House, SAGE Publishers for publishing our Journal of Neonatology from

next year ( 2018 ). This MOU with fundamentally strong Publishing House is expected to catapult our

Journal to great heights and we visualise that shortly it will be ranked at par with Best International

Journals in Neonatology. I request all the members to bring back the journal on progressive path,

contribute your good work to your own journal. I am sure you will all cooperate in this academic

endeavour of your own society.

We are happy to inform you that NNF conducted lot of activities during this year-FBNC workshops in

various districts of MP State supported by MP Government, FBNC workshops supported by UNICEF

Odisha, monthly clinical meetings conducted by NNF in various hospitals of Delhi, UNICEF supported

activities-Database workshops, Accreditation TOT, Expert Group Meetings for revision of Clinical

Practice Guidelines, Mentoring visits, Accreditation of various SNCUs, etc. We take pride in informing th th thyou that the 37 Annual Conference of the NNF “The NEOCON 2017” will be held from 8 to 10

December, 2017 in Hotel Lemon Tree Complex, Gurgaon (NCR). We look forward to welcoming you for

this mega conference.

Current Issue that is in your hands is dedicated to various aspects of CPAP and Non - Invasive Ventilation.

Very Interesting article -Unusual Caesarean Delivery, Neonatal Osteomyelitis and spontaneous Umbilical

Haematoma are real Eye - Openers. I am sure that you will definitely like the matter presented and enjoy

reading each and every page of this issue.

Alok Bhandari

Editor-in-Chief

Editorial

1

Journal of Neonatology Volume 31 / Issue I & II / January - June 2017

Abstract

Background of the study

We implemented ‘early CPAP’ (LR CPAP and early

extubation policy) in 2007-2008 in our unit and evaluated

the change in respiratory care of preterms in the era after

and before early CPAP.

Objectives

To evaluate the implementation and impact of ‘early

CPAP’ {LR CPAP and policy on early extubation} in

preterm babies £ 33 weeks.

Study design: Case Control study.

Study period: Two time epochs before (July 2010 to June

2011) and after (September 2006 to August 2007)

introduction of ‘early CPAP’

Settings: Referral NICU in a private sector hospital

Participants: All live born intramural neonates £ 33

weeks.

Intervention

1. Use of LR CPAP (T-piece resuscitator)

2. Policy on early extubation to CPAP

Main outcome measures

• Assessment of implementation

• Decreased need for Intubation in LR

• Time to extubation

• Assessment of effect

• Mean duration on respiratory support

• Survival

Results

96 cases were enrolled prospectively and 53 cases were

enrolled as historic controls. The number of babies who

required intubation in the labour room decreased by 50%

(9.2 % Vs 18.9%) in the ‘early CPAP’ group when

compared to controls. Median time on invasive ventilation th thdecreased. It was 14 hrs (5-66, 25 –75 quartile) vs

th thmedian 48 hrs (18-96, 25 –75 quartile) in ‘early CPAP’

group and controls, respectively. More babies were

extubated earlier (45.1% vs 21.1% by 12 hours and 70.6%

vs 36.9 % by 36 hours) in early CPAP group. Early CPAP

decreased the need for respiratory support (intubation +

CPAP time) (42 % vs 23 % by 24 hrs and 67% vs 41 % by 48

hrs) with no decrease in survival of very preterm babies.

Conclusions: Early CPAP decreases need for respiratory

support without decrease in survival.

Key words: Delivery room CPAP, early extubation

Introduction

For two decades, the standard treatment for respiratory

distress syndrome in preterm infants has been intubation, 1,2ventilation and surfactant. However, since ventilation

Impact of Early CPAP on the Respiratory Care ofPreterm Babies - An Audit

Naveen Jain, Jemila James

Corresponding author: Dr Naveen Jain, Consultant Neonatologist,Department of Pediatrics & Neonatology,Kerala Institute of Medical Sciences,Trivandrum, Kerala, IndiaKGRA 61/3, Kallumoodu Gardens,Anayara PO, Trivandrum, Kerala, PIN -695029 Email: [email protected]

Research Article

2


3,4may damage the lungs, nasal CPAP is fast replacing

invasive ventilation. Observational studies in clinical

practice have suggested that use of CPAP in LR instead of 2intubation may reduce the need for intubation . Babies

who need intubation and surfactant are also extubated

shortly to CPAP, this reduces the time to extubation.

We tested the implementation of early CPAP (labor room

CPAP and early extubation to CPAP) in our unit. We

evaluated impact of use of early nasal CPAP in our NICU in

this audit comparing the two time epochs before and after

purchase of T-piece resuscitator and policy on early

extubation.

Aims & objectives

To evaluate implementation (decrease in need for

intubation and time to extubation) and impact (decrease in

need for respiratory support without increase in mortality)

of early CPAP {LR CPAP and policy on early

extubation}in preterm babies d” 33 weeks

Method of the study: Study

Design: Case Control study.

Duration of the study: 2 years

Cases: Preterm babies £ 33 weeks managed in our NICU

after introduction of early CPAP (July 2010 to June 2011)

Controls: Preterm babies £ 33 weeks managed in our

NICU before introduction of early CPAP (September 2006

to August 2007)

Place of study: A tertiary care referral centre is a part of

referral perinatology service in a private sector hospital

and has the infrastructure necessary to manage sick

neonates – ventilators, surfactant, facilities for parenteral

nutrition, trained manpower, protocols, etc. The NICU

was accredited as a teaching unit by NBE and IAP for

speciality training in neonatology in 2008.

Subjects: All live born intramural neonates £ 33 weeks,

irrespective of birth weight.

Intervention

1. Use of LR CPAP (T-piece resuscitator)

2. Policy on early extubation to Ncpap

Main outcome measures

• Assessment of implementation of early CPAP

• Decrease for need for Intubation in LR

• Time to extubation

• Assessment of effect of early CPAP

• Mean duration on respiratory support (ventilator

+ CPAP time)

• All cause mortality

Study protocol

In KIMS, all preterm babies (< 33 weeks) with significant

respiratory distress* receive intubation and surfactant.

The unit was not still practising aggressive trial of CPAP

before deciding to intubate and give surfactant.

• Before introduction of early CPAP: Preterms with

significant respiratory distress* were intubated in LR

and transferred to NICU and surfactant administered

in NICU after assessment.

• After introduction of early CPAP (T-piece

resuscitator): Preterms with significant respiratory

distress were started on LR CPAP (unless intubation

was necessary for resuscitation or for poor respiratory

efforts or hypoxia and bradycardia) and transferred to

NICU and intubation and surfactant administered in

NICU if there was severe respiratory distress*.

• Early extubation policy: Babies were extubated to

CPAP after surfactant therapy if baby had good

respiratory efforts and was on minimal settings**

within few hours.

*severe respiratory distress warranting intubation and

surfactant and minimal settings** on ventilator

allowing trial of extubation were not pre-defined

(retrospective audit) and based on individual

assessment.

The details were collected from the files of MRD,

KIMS, Trivandrum. Institution permission was

obtained to use patient data for research.

Statistical analysis

Descriptive statistics were used to describe baseline

variables. Categorical outcome variables were analyzed

by Chi square test. P value < 0.05 was taken as significant.

Statistical analysis was done using statistical software

packages SPSS version 17.0 and Microsoft Excel.

3


Results

Table 1: Population Characteristics:

Prospective Historical

Early Control group

CPAP group

Gestational £ 26 11 (11.5%) 6 (11.3%)

Age (weeks) 27 – 28 17 (17.7%) 2 (3.8%)

29 -30 12 (12.5%) 14 (26.4%)

31 – 33 56 (58.3%) 31 (58.5%)

birth £ 1000 19 (19.8%) 10 (18.9%)

weight (gm) 1001 – 1500 34 (35.4%) 16 (30.2%)

>1500 43 (44.8%) 27 (50.9%)

P value= 0.029

Table 2. Audit of Implementation of early CPAP

Prospective Historical

Early CPAP Control

group group

Babies LR 8 (9.2%) 10 (18.9%) P value

who intubation = 0.067

required NICU 36 (41.4%) 13 (24.5 %)

intubation intubation

Time to In 12 hrs 23 (45.1%) 4 (21.1%) P value

extubation = 0.038

13-36 hrs 36 (70.6%) 7 (36.9%)

37-96 hrs 44 (86.3%) 16 (84.3%)

>96 hrs 51 (100%) 19 (100%)

Flow chart

Preterm £ 33 wks with severe respiratory distress

Historical control group Prospective cohort-early CPAP group

n = 53 n = 96

Intubated in labor room LR CPAP

Surfactant in NICU

Ventilation for 1-3 days Intubated poor respiratory Reassess in

effort Or bradycardia NICU

Severe respiratory distress No respiratory distress

Intubate & give surfactant

Consider extubation

In hours

4


Table 3. Impact of early CPAP on respiratory morbidity

and mortality

Early Control P value

CPAP group

group

Off £ 24 hrs 24 (42%) 5 (23%) 0.06

respiratory £ 48 hrs 38 (67%) 9 (41%)

support < 5 days 46 (81 %) 18 (82%)

(Ventilation > 5 days 57 (100 %) 22 (100 %)

+ CPAP

time)

Death and 17 (17.7 %) 7 (13.2) P = NS

or CLD Died 13 (13.8%) 7 (13.2%)

On oxygen 4 0

> 28 days

Discussion

There were 96 babies in the epoch of early CPAP and

compared with 53 babies from the epoch before

introduction of early CPAP to our NICU.

Babies in the prospective cohort early CPAP group were

more preterm, between 27-28 weeks of GA were 17.7% Vs

3.8% in the control group (P value 0.029).

The babies who required intubation in the labour room has

been dramatically reduced by 50% in the early CPAP group

after the introduction of T-piece resuscitator in our unit

when compared to controls. (9.2 % Vs 18.9% in controls).

The early extubation policy succeeded in decreasing time

to extubation. Median time on invasive ventilation th thdecreased, median 14 hrs (5-66, 25 – 75 quartile) vs

th thmedian 48 hrs (18-96, 25 – 75 quartile) in early CPAP

group compared to controls. More babies were extubated

(45.1% vs 21.1% by 12 hours and 70.6% vs 36.9 % by 36

hours) in the early CPAP group.

It was possible that early extubation of babies was merely

replaced by longer time on CPAP. Hence, we studied the

total time on respiratory supports - (including ventilation

& CPAP). When we compared early CPAP group to

historical controls, (42 % vs 23 %) babies were off

respiratory support by 24 hrs of age, and (67% vs 41 %) by

48 hrs age.

The introduction of labor room CPAP and early extubation

policy succeeded in decreasing time to extubation and

total time on respiratory supports with no decrease in

survival rates.

In the randomized, controlled Continuous Positive Airway 5Pressure or Intubation at Birth (COIN) trial , the

intubation rate for the CPAP group was 40% for those born

at 27 or 28 wks gestation. The median time for intubation

was 6.6hrs.

6 Poets and Sens et al. have shown a decrease in the

incidence of early intubation and ventilation in very-low-

birth-weight infants who received early CPAP. The

proportion of not intubated and ventilated increased from

28% to 44% in infants weighing more than 999 g.

7Jacobsen and colleagues described a cohort study, with

historical controls, demonstrated a significant reduction in

the frequency of mechanical ventilation from 76% in the

control group to 35% in the study group. The difference in

mortality rate, and number of surviving infants with

handicap did not differ significantly between the two study

periods.

8Aly and colleagues conducted a retrospective study on

infants supported with early nasal CPAP. Their study

showed CPAP was not successful at less than 24 wks GA,

but the success rate was improved significantly by 25 wks.

Also they have shown in their study the babies supported

with CPAP in the delivery room had a shorter duration of

oxygen requirement than babies who are intubated in the

delivery room and treated with CPAP within the first 48

hours. No babies developed IVH or ROP in the delivery

room CPAP group.

9Gittermann and colleagues examined the use of early

(defined as the onset of respiratory distress, usually within

15 minutes of birth) CPAP. The rate of intubation

decreased from 53% (before use of CPAP) to 30% (when

they introduced a policy of using CPAP for spontaneously

breathing neonates manifesting signs of respiratory

distress), but the rate of chronic lung disease did not

change significantly (32% versus 30%). None of the

potential sequelae of CPAP were noted in their study.

10De Klerk and De Klerk reported from a historical cohort

study and showed a significant reduction in the number of

infants ventilated (65% to 14%), number of infants

receiving surfactant (40% to 12%) and median days of

ventilation (6 to 2) and oxygen (4 to 2) before and after the

change in respiratory support policy. There were decreases

in chronic lung disease at 28 days (11% to 0%) and in death

or chronic lung disease at 28 days (16% to 3%).

5


Conclusions

• LR CPAP has reduced the need for intubation in the

labour room

• LR CPAP and early extubation policy has reduced the

time to extubation

• Early CPAP has decreased need for respiratory

supports (CPAP & ventilation) with no decrease in

survival.

References

1. Hansen TN, Corbet A. Disorders of transition. In: Taeusch

HW, Ballard RA, eds. Avery’s diseases of the newborn. 7th

ed. Philadelphia: Saunders, 1998:602-29.

2. Lindner W, Vossbeck S, Hummler H, Pohlandt F. Delivery

room management of extremely low birth weight infants:

spontaneous breathing or intubation? Pediatrics

1999;103:961-967 CrossRef | Web of Science | Medline

3. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J

Respir Crit Care Med 2001;163:1723-1729 Medline

4. Kraybill EN, Runyan DK, Bose CL, Khan JH. Risk factors

for chronic lung disease in infants with birth weights of 751

to 1000 grams. J Pediatr 1989;115:115-120 CrossRef | Web

of Science | Medline

5. Colin J. Morley, M.D., Peter G. Davis, M.D., Lex W. Doyle,

M.D., Luc P. Brion, M.D., Jean-Michel Hascoet, M.D., and

John B. Carlin, Ph.D. for the COIN Trial Investigators .

Nasal CPAP or Intubation at Birth for Very Preterm Infants.

N Engl J Med 2008; 358:700-708February 14, 2008

6. Poets CF, Sens B. Changes in intubation rates and outcome

of very low birth weight

7. Infants: a population-based study. Pediatrics 1996;98:24 –

7.

8. Jacobsen T, Gronvall J, Petersen S, et al. ‘‘Minitouch’’

treatment of very low-birth-weight infants. Acta Paediatr

1993;82:934– 8.

9. Aly H, Massaro AN, Patel K, et al. Is it safer to intubate

premature infants in the delivery room? Pediatrics 2005;

115:1660– 5.

10. Gittermann MK, Fusch C, Gittermann AR, et al. Early nasal

continuous positive airway pressure treatment reduces the

need for intubation in very low birth weight infants.

11. Eur J Pediatr 1997; 156:384–8.

12. 10. De Klerk AM, De Klerk RK. Nasal continuous positive

airway pressure and outcomes of preterm infants. J Paediatr

Child Health 2001; 37:161– 7.

STATE BRANCH ACTIVITY REPORT

BREAST FEEDING PROGRAM

NEWBORN WEEK

The 37th Annual Convention of National Neonatology Forum (NEOCON 2017) is scheduled to be held on 8th to 10th

December, 2017 at Gurugram, Haryana.Best Branch Award for the NNF activities for the year, Best Branch Award

for conducting Newborn Week and Best Branch Award for Breast Feeding Week will be announced during Annual

Convention of NNF (NEOCON 2017). All States and Territory Branch of NNF are requested to send their activity

report& Breast Feeding Week Report latest by 25thOctober, 2017.Last date for sending report of Newborn Week is

25thNovember, 2017. Please send your report in word format as attachment.

Dr. B.D. Bhatia Dr. Ajay Gambhir Dr. Alok Bhandari Dr. Lalan K. Bharti

President Imm. Past President Secretary Jt. Secy. cum Treasurer

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National Neonatology Forum of India

6


Abstract

Background-Humidified high flow nasal cannula

(HHFNC) is being increasingly used as an alternative

form of respiratory support for preterm infants with apnea,

respiratory distress syndrome or chronic lung disease,

even though limited evidence is available to support the

specific role, efficacy, and safety in newborns.

Objective-To study the effect of high flow support in

preterm infants born at 30-32 weeks gestation with

primary respiratory disease or post-extubation.

Materials and Methods- A retrospective database review

audit of infants treated with HHHFNC was obtained and

compared with infants treated with NCPAP during the

study period of 1 year. The primary outcome measures

assessed were death, days on mechanical ventilation, need

for reintubation (failure), air leak and Bronchopulmonary

dysplasia.

Results-Treatment failure (Re-Intubation) was seen in 9%

of infants on HHHFNC compared to 19% on NCPAP (P

value=0.24). No significant difference in other outcome

measures seen between the groups. No nasal injury was

seen in HHHFNC group against 5% in NCPAP group (P

value=0.54).

Conclusion-High flow support appears safe to use in

moderate preterm infants. Larger trials are needed to find

its utility in very preterm infants and infants with severe

respiratory disease.

Keywords: NCPAP, high flow nasal cannula, neonate,

respiratory distress or disease, postextubation

Abbreviations: NCPAP-Nasal Continuous positive

airway pressure, HHHFNC-heated humidified high flow

nasal cannula, RDS-respiratory distress syndrome.

Introduction

Respiratory failure in the neonatal period remains a

difficult challenge and is associated with high morbidity,

mortality and cost. The current practice of most

neonatologists reflects the belief that limited exposure to

invasive mechanical ventilation and careful use of oxygen

support result in less lung injury and improved long-term 1, 2, 3pulmonary outcomes in premature infants. Respiratory

support to preterm infants with apnea or parenchymal lung

disease can be provided through variety of non-invasive

ways. These include oxygen via a head box or nasal

cannula; nasal continuous positive airways pressure

(NCPAP) and nasal intermittent positive pressure

ventilation (NIPPV).

Nasal cannula are a means of administration of oxygen or

blended oxygen and air via two small, thin, tapered tubes

(usually less than 1 cm in length) that sit just inside the 4nostrils without occluding them. Oxygen delivered by

’low flow’ nasal cannula (LFNC) typically refers to the use

of flow rates of less than or equal to 2L/minute. Usually the

gas used is unblended (100% oxygen), unheated and non-

humidified and was traditionally supposed to be effective 5form of respiratory support. In contrast, ’high flow’ nasal

cannula (HFNC) have been used to refer to the

High-Flow Nasal Cannula Versus CPAP for

Respiratory Support in Preterm Infants

Abdul Razak, Siddu Charki, N Karthik Nagesh

Corresponding author:

Dr. N. Karthik Nagesh

Chairman-HOD of Neonatology

Professor of Pediatrics, Manipal University, India.

Manipal Advanced Children’s Centre (MACC),

Manipal Hospitals, Bangalore

E-mail: [email protected],

[email protected]

Research Article

7


administration of blended oxygen to newborn infants via

nasal cannula at higher flow rates than with LFNC. HFNC

is defined as the use of flow rates of greater than

2L/minute. The use of high flow rates in preterm infants 6, 7, 8may provide positive end-expiratory pressure (PEEP).

Oxygen administered via HFNC is usually blended with 9air, heated and humidified. HFNC have been suggested as

an alternative form of respiratory support for preterm

infants with apnea, respiratory distress syndrome or 10chronic lung disease.

Nasal continuous positive airway pressure (CPAP) is

widely used in premature and term newborns and provides 11an effective, safe alternative to endotracheal intubation.

It has been shown to reduce extubation failure, treat apnea

and respiratory distress syndrome and may reduce chronic

lung disease by minimizing duration of mechanical 12ventilation. The most effective and popular means of

11administering CPAP is by using short binasal prongs.

These prongs are designed to fit snugly into the infant’s

nostrils with minimal leakage. By contrast, nasal cannula

do not usually occlude the nostrils and have the potential

for a large leak around them. Other interfaces for

delivering CPAP to the nose that are in common use

include single nasal prongs and nasal masks. Oxygen

administered by nasal CPAP is usually blended,

humidified and heated. As opposed to HFNC, the pressure

delivered by the circuit for nasal CPAP is measured and 13 regulated directly. unfortunately both systems may have

adverse effects. The use of binasal prongs to deliver CPAP

is associated with trauma to the nasal septum and 8, 14distortion of the nares. It has been thought that HFNC

10may cause less nasal injury, however the use of

humidified, unheated HFNC has been associated with

mucosal irritation, nasal obstruction or bleeding as well as 15, 16a possible increase in the risk of nosocomial infection.

The effects of the introduction of HHFNC on outcomes

such as duration of supplemental oxygen, mechanical

ventilation-days, bronchopulmonary dysplasia (BPD),

hospital length of stay (LOS) and mortality, among other

measures, have not been formally assessed. Furthermore,

in the absence of an accepted way to monitor end-

expiratory pressure, it is unclear if HHFNC is

inadvertently generating high pressures and causing

unrecognized lung damage, particularly in the smaller

preterm infants. The purpose of this study is to assess the

indications, frequency of usage and safety of humidified

high flow nasal cannula (HHFNC) in neonates in tertiary

level NICU and compare outcomes.

Methodology

We performed a retrospective database review audit of

infants treated with HHHFNC from June 2013 to May

2014. Infants treated with NCPAP during the same period

were compared with respect to the outcome measures. The

study was performed at a tertiary III-B level care neonatal

intensive care unit in South India. Infants were included if

they were 30-32 weeks gestational age (GA) and inborn or

transferred to our center within the first 24 h of life. To

meet the study criteria, infants had to be placed on one of

the respiratory support modalities of interest (NCPAP or

HHFNC) either initially following admission for primary

respiratory disease or immediately following extubation

from mechanical ventilation within 96 h of birth. Infants

were treated on either form of respiratory support based on

clinician discretion. Failure was defined as requirement of

fiO2 >50% to maintain PaO2 >60%, respiratory acidosis-

pH<7.25 with PacO2>60 mmHg. Nasal CPAP support was

provided by using interface Hudson Prongs (Teleflex

Medical Research Triangle Park, NC 27709 USA) with

pressure generation by Drager ventilator (Drager Medical

AG and Co.KG 23542 Lubeck, Germany) utilizing

pressures ranging from 5 to 7 cm H2O. The flows used

were 5-6L/min delivered using the Fisher and Paykel

Neonate Nasal Cannula (1.5mm internal diameter)

through the Fisher and Paykeloptiflow junior kit [RT 330,

Maurice Paykel Place, East Tamaki, Auckland, New

Zealand]. The fraction of inspired oxygen (FiO2) was

adjusted according to center protocol targeting oxygen

saturations between 91% and 95%. Exclusion criteria

included s ignif icant congenital heart disease,

chromosomal abnormalities, genetic syndromes or other

major congenital malformations.

Outcomes measures of interest included death, days on

mechanical ventilation, need for reintubation, air leak,

BPD (defined as an ongoing requirement for supplemental

oxygen at 36 weeks corrected gestational age), necrotizing

e n t e r o c o l i t i s ( N E C , e i t h e r d o c u m e n t e d

pneumatos i s in tes t ina l i s o r r equ i r ing su rg ica l

intervention), severe intraventricular hemorrhage (IVH

grade 3 or 4), retinopathy of prematurity (ROP), days to

full feeds (120 ml/kg/day) and culture positive sepsis.

Statistical analyses included Student’s t-test for

continuous data and Fisher’s exact test and Chi Square test

for categorical data. P-values less than 0.05 were

considered statistically significant.

8


Results

During the study period, 93 of 358 (26%) infants born at

30-32 weeks of gestational age received either early

NCPAP or HHFNC. Twenty (18%) infants were excluded

from study group due to either prolonged intubation (>96

h) or death before extubation. A total of 32 infants were

treated with HHHFNC against 61 infants treated with

NCPAP (Flow chart 1). There were no differences noted in

the baseline characteristics between the comparison

groups such as mean gestation, birth weight, and gender

distribution (Table 1). Analysis for selected outcomes in

these infants supported on either NCPAP or HHFNC as an

early mode of respiratory support within the first 96 h of

life showed the majority of infants were initially supported

by mechanical ventilation for 1 to 2 days with no

significant difference. There were no significant

differences in major clinical outcomes including death,

BPD, ventilator-days, NEC, severe IVH, ROP or time to

full feeds (Table 2).Although, there was reduced nasal

injury in HHFNC group compared to CPAP group (5% vs

0%), the numbers were small to prove the significance.

Table 1: Characteristics of infants included in the analysis

NCPAP HHFNC P value

Number of infants 61 32

Gestational Age

(weeks, mean±s.d.) 30±1.1 31±0.8 0.55

Birth weight

(g, mean±s.d.) 1250±150 1360±140 0.5

Male (%) 65 60 0.5

Inborn (%) 73 70 0.5

Cesarean

section (%) 72 67 0.3

Singleton (%) 92 89 0.5

Delivery room

intubation (%) 74 68 0.6

Received

surfactant (%) 81 77 0.6

Ventilator-days

pre-NCPAP/

HHFNCb 1.7±1.5 1.5±1.3 0.89

NCPAP days

per infant

Total infants

(mean) 23 -

HHFNC days

per infant

Total infants

(mean) - 29

Discussion

The use of HHFNC has increased in many NICUs over the

past several years. Potential reasons for this increase

include its ease of use and perceived improved tolerance

with minimal nasal trauma compared to NCPAP. Clinical

outcomes associated with the use of HHFNC are

anecdotally perceived by some neonatologists to be at

least similar to those of NCPAP usage. Although HHFNC

has been widely accepted clinically, there is sparse data

regarding its efficacy and safety. One published trial exists

comparing Humidified high-flow nasal cannula (HHFNC)

with NCPAP in which HHFNC was shown to be as 8efficacious as NCPAP in preventing apnea of prematurity.

Otherwise there have been only a few studies with small

patient numbers reported to date describing the safety of

this modality compared to NCPAP in premature infants,

and no controlled clinical trials evaluating its utility in this 17-21population.

Flow chart 1-Retrospective cohort

358 infants

³32weeks 30-32 weeks

113 245

Excluded-20

(Prolonged

intubation/death)

Received NCPAP Received HHFNC

Within 96 hours of birth within 96 hours of birth

61 32

9


Table 2: Outcomes of infants in the analysis

NCPAP HHFNC P value

Number of infants 61 32

Hospital stay

(days, mean±s.d) 25±15 23±19 0.55

GA at discharge

(weeks, mean±s.d) 38.4±3.3 38.7±3.6

Time to full feeds

(days, mean±s.d) 17.3±12 14.6±11 0.55

Deaths (%) 1 0 1

Pneumothorax (%) 0 0 1

IVH>2 (%) 3/61 (5) 1/32(3) 1

NEC (%) 5/61(8) 2/32(6) 1

Total ventilator-

days per patient

(mean±s.d) 9.3±9.6 8.5±9.2 0.9

(Re)Intubation (%) 12/61(19) 3/32(9) 0.24

BPD (%) 11/61(18) 4/32(12) 0.56

Any ROP (%) 5/61(8) 2/32(6) 1

Nasal Injury 3/61(5) 0(0) 0.54

By comparison to historical data before its widespread introduction, HHFNC appears to be well tolerated and provides similar outcomes when compared to NCPAP. Death and BPD rates were similar for premature infants before and following the introduction of HHFNC, and

22 there was a decrease in ventilator-days. when infants 30-32 weeks GA were compared by early mode of respiratory support (NCPAP or HHFNC) - outcomes were similar. There were no statistically significant differences in ventilator-days, deaths, infections, IVH or LOS. There is debate whether early NCPAP decreases the risk of BPD in

22-26infants <32 weeks GA. Our data did not show a difference in BPD rates between the NCPAP and HHFNC groups. The majority of infants in study period included in the analysis were intubated for 1 to 2 days before receiving either NCPAP or HHFNC and outcomes in these infants were not different.

There are existing concerns among neonatologists regarding the widespread application and usage of HHFNC in premature infants in the absence of sufficient published literature supporting its utility and safety. Particular concern has focused on the imprecise regulation and generation of pressure that may occur at higher flows,

especially in the smallest of infants, as well as the potential for a significant increased work of breathing with HHFNC

27-30devices as compared to nCPAP. Of interest, a recently published small randomized trial did not show increased work of breathing or respiratory rates of preterm infants <2 kg on HHFNC (3 to 5 LPM) compared to preterm infants

10receiving NCPAP set at 6 cm H2O.

Additionally, recorded esophageal pressures were consistently <4 cm H2O at flow rates of 3 to 5 LPM, similar

6to delivered NCPAP pressures. Previously, Locke et al. reported that as much as 9 cm H2O pressure measured by esophageal balloon manometer can be generated with as little as 2 LPM HHFNC in 3 mm cannula but not in 2 mm cannula. The cannula used in our infants were 1.5 mm, and although we did not quantify pressure, pressures generated did not appear to be excessive based on clinical evaluations including serial chest radiographs. One recent report looking at airway pressure generated in preterm infants with the Vapotherm device found a high pressure of

31only 4.5 cm H2O with up to 8 LPM of flow. In our study, no infant supported with HHFNC during their hospitalization had a pneumothorax/air leak while on this respiratory mode. Further studies measuring airway pressure generated with HHFNC devices in premature neonates, to include how pressures vary with weight and at different flow rates, need to be done.

Although this study is limited by its relatively small sample size and inclusion of only those infants less than 32 weeks GA, the data presented here indicate that HHFNC may represent a well-tolerated and effective alternative respiratory support mode to NCPAP in the preterm infant population. Possibility of selection bias is also one of the other limiting factor as the selection of cases was by clinician discretion criteria. The potential advantages of HHHFNC include its simplicity, improved tolerability with less injury to the nasal architecture and mucosa and perhaps greater clinical utility in managing respiratory distress in premature infants. However, the paucity of published outcomes to date, the safety and utility of HHFNC as compared to more traditional respiratory support modes remains unproven and needs to be further investigated. The ethicality of using HHFNC, instead of CPAP, as a primary modality when there is no pressure predictability is also an issue to be addressed. Two RCTs-The HUNTER trial and The HIPSTER Trialarebeing conducted to investigate the efficacy of HHFNC in preterm infants. Our study has shown high flow support to be safe to use in moderately preterm infants. However, larger trials are needed to find its utility in very preterm infants and infants with severe respiratory disease.

10


References

1. Angus DC, Linde-Zwirble WT, Clermont G, Griffen MF, Clark RH.Epidemiology of neonatal respiratory failure in the United States. Am J RespCrit Care Med 2001; 164: 1154–1161

2. Hudson LD. Progress in understanding ventilator-induced lung injury.JAMA 1999; 282: 77–78.

3. Jobe AH, Ikegami M. Mechanisms initiating lung injury in the preterm infant.Early Hum Dev 1998; 53: 81–94.

4. Frey B, Shann F. Oxygen administration in infants. Archives of Disease in Childhood.Fetal and Neonatal Edition 2003;88:F84–8.

5. Walsh M, Engle W, Laptook A, Kazzi SN, Buchter S, RasmussenM, et al.Oxygen delivery through nasal cannula to preterm infants: can practice be improved?. Pediatrics 2005;116:857–61.

6. Locke RG, Wolfson MR, Shaffer TH, Rubenstein SD, Greenspan JS. Inadvertent administration of positive e n d d i s t e n d i n g p r e s s u r e d u r i n g n a s a l c a n n u l a flow.Pediatrics 1993;91:135–8.

7. Frey B, McQuillan PJ, Shann F, Freezer N. Nasopharyngeal oxygen therapy produces positive end-expiratory pressure i n i n f a n t s . E u ro p e a n J o u r n a l o f P e d i a t r i c s 2001;160:556–60.

8. Sreenan C, Lemke RP, Hudson-Mason A, Osiovich H. High-flow nasal cannula in the management of apnea of prematurity: a comparison with conventional nasal continuous positive airway pressure. Pediatrics 2001;107: 1081–3.

9. Waugh JB, Granger WM. An evaluation of 2 new devices for nasal high-flow gas therapy.Respiratory Care 2004;49: 902–6.

10. Saslow JG, Aghai ZH, Nakhla TA, Hart JJ, Lawrysh R, Stahl GE, et al.Work of breathing using high-flow nasal cannula in preterm infants. Journal of Perinatology 2006;26: 476–80.

11. Morley C, Davis P. Continuous positive airway pressure: current controversies. Current Opinion in Pediatrics 2004;16:141–5.

12. De Paoli AG, Morley C, Davis PG. Nasal CPAP for neonates: what do we know in 2003?.Archives of Disease in Childhood. Fetal and Neonatal Edition 2003;88:F168–72.

13. De Paoli AG, Davis PG, Faber B, Morley CJ.Devices and pressure sources for administration of nasal continuous positive airway pressure (NCPAP) in preterm neonates. Cochrane Database of Systematic Reviews 2008, Issue 1. [DOI: 10.1002/14651858.CD002977.pub2]

14. Robertson NJ, McCarthy LS, Hamilton PA, Moss AL. Nasal deformities resulting from flow driver continuous positive airway pressure. Archives of Disease in Childhood.Fetal and Neonatal Edition 1996; 75:F209–12.

15. Kopelman AE. Airway obstruction in two extremely low birthweight infants treated with oxygen cannulas. Journal ofPerinatology 2003;23:164–5.

16. Kopelman AE, Holbert D. Use of oxygen cannulas in extremely low birthweight infants is associated with mucosal trauma and bleeding, and possibly with coagulase-

negative staphylococcal sepsis. Journal of Perinatology 2003;23:94–7.

17. Nair G, Karna P. Comparison of the effects of Vapotherm and nasal CPAP in respiratory distress in preterm infants. PediatrAcadSoc 2005; 57: 2054.

18. Ovalle OO, Gomez T, Troncoso G, Palacios J, Ortiz E. High flow nasal cannula after surfactant treatment for infant respiratory distress syndrome in preterm infants <30 weeks. PediatrAcadSoc 2005; 57: 3417.

19. Ramanathan A, Cayabyab R, Sardesai S, Siassi B, Seri I, Ramanathan R. High flow nasal cannula use in preterm and term newborns admitted to neonatal intensive care unit: A prospective, observational study. PediatrAcadSoc 2005; 57: 3424.

20. Sanchez F, Sabato K. Very high nasal cannula-alternative to NCPAP in select ICN patients? Respir Care 2004; 49: 1373.

21. Holleman-Duray DL, Kaupie DL, Weiss MG. Safety and efficacy of the Vapotherms high flow humidification system and an early extubation protocol. PediatrAcadSoc 2006; 59: 517.

22. Rich W, Finer NN, Vaucher YE. Ten-year trends in neonatal assisted ventilation of very low- birthweight infants.J Perinatol 2003; 28: 660–663.

23. Jegatheesan P, Keller RL, Hawgood S. Early variable-flow nasal continuous positive pressure in infants < or¼1000 grams at birth. J Perinatol 2006; 26: 189–196.

24. Aly H, Milner JD, Patel K, El-Mohandes AA. Does the experience with the use of nasal continuous positive airway pressure improve over time in extremely low birth weight infants? Pediatrics 2004; 114: 697–702.

25. Narendran V, Donovan EF, Hoath SB, Akinbi HT, Steichen JJ, Jobe AH. Early bubble CPAP and outcomes in ELBW preterm infants.J Perinatol 2003; 23: 195–199.

26. Davis PG, Henderson-Smart DJ. Post-extubation prophylactic nasal continuous positive airway pressure in preterm infants: systematic review and meta-analysis. J Paediatr Child Health 1999; 35: 367–371.

27. Chang GC, Cox CC, Shaffer TH. Nasal cannula, CPAP, and Vapotherm: effect of flow on temperature, humidity, pressure and resistance. PediatrAcadSoc 2005; 57: 1231.

28. Courtney SE, Pyon KH, Saslow JG, Arnold GK, Pandit PB, Habib RH. Lung recruitment and breathing pattern during variable versus continuous flow nasal continuous positive airway pressure in premature infants: an evaluation of three devices. Pediatrics 2001; 107: 304–308.

29. Finer NN. Nasal cannula use in the preterm infant: oxygen or pressure? Pediatrics 2005; 116: 1216–1217.

30. Walsh M, Engle W, Laptook A, Kazzi SNJ, Buchter S, Rasmussen M et al. Oxygen delivery through nasal cannula to preterm infants: can practice be improved? Pediatrics 2005; 116: 857–861.

31. Kubicka Z, Limauro J, Darnall R. High flow nasal cannula therapy with Vapothem: yet another way to deliver CPAP? PediatrAcadSoc 2006; 59: 5660.344.

11


Abstract

Aim: To assess the feasibility of using of pulse oximetry as

a screening tool to identify early-onset sepsis (EOS) in

asymptomatic newborns.

Study Design: Prospective cohort study.

Place and Duration of Study: Manipal hospital and

Motherhood hospital Bangalore, India, between April and

June 2013.

Methodology: All asymptomatic newborns born after 35

weeks gestational age were screened on two occasions

using pulse oximetry. Newborns with oxygen saturations

below predefined thresholds (reading below 90% or the

repeat readings remained between 90 to 94%) were

defined as test positive and all these babies underwent a

septic screen which included full blood count, C-reactive

protein, blood cultures and chest x-ray. Test negative

newborns were followed up in the out patient department

to ascertain if they were diagnosed to have sepsis in the

first week.

Results: A total of 213 eligible newborns were screened.

Two (2/213, 0.93%) newborns tested positive and both

were diagnosed with early onset sepsis. All test negative

newborns were followed up and none had evidence of early

onset sepsis at follow up.

Conclusion:. This study demonstrates that it is feasible to

use pulse oximetry to screen for early onset sepsis in

asymptomatic newborns

Keywords: Pulse oximetry; neonate/newborn; early-onset

neonatal sepsis; screening.

Introduction

Every year about 3 million newborns worldwide die within

the first week of life, a quarter of these as a result of sepsis

and pneumonia [1]. Symptoms of early-onset sepsis

(EOS), which is defined as infection occurring within the

first 3 days of life, often occurs within the first 24 hours

after birth [2, 3]. The incidence of neonatal sepsis in India

is a high as 30 per 1000 live births, [4] and the diagnosis of

EOS is often missed due to non-specific or absent signs

and symptoms [5].

Hypoxaemia, a reduction of the oxygen concentration in

arterial blood, [6] is strongly associated with sepsis and is

seen in one-third of septic neonates [7, 8 and 9]. Pulse

oximetry measures oxygen saturation and is a simple,

reliable and accurate method for detecting hypoxaemia

[10]. Pulse oximetry is been increasingly used as a

screening tool for newborn congenital heart defects.

[11–14] A recent study highlighted the role of pulse

oximetry as a screening tool to detect early-onset sepsis in

a low-income setting [15]. Reduction in mortality has been

shown by the utility of pulse oximetry by detecting

hypoxemia early in conditions like pneumonia [16, 17].

The aim of this study is to evaluate the feasibility of

undertaking pulse oximetry to identify EOS in

asymptomatic newborns in a tertiary unit setting in India.

Pulse Oximetry as Screening Test for Early-onset Sepsis

in Newborns in Tertiary Hospitals in India

* * * * *R. Swamy , A Razak , P. Mohanty , P K Venkatagiri , H A Venkatesh ,

* ** ***N Karthik Nagesh , AK. Ewer , S. Thangaratinam*Department of Neonatology, Manipal Hospital, Bangalore, India

**Birmingham Womens Hospital, Edgbaston, Birmingham, UK***Queen Mary University of London, London, UK


Dr. Ravi Shankar Swamy

Department of Neonatology,

Manipal Hospital,

Bangalore.

[email protected]

Research Article

12


Methods

This observational study was carried out at Manipal

hospital and Motherhood hospital, Bangalore between 1st stApril and 31 June 2013. Bangalore is a large city with a

population around 4 million is located in South India, and

these hospitals are tertiary referral centres. There are

approximately 4,000 deliveries per year, collectively.

All asymptomatic neonates more than 35 week’s gestation

were eligible for the study. Saturation measurement was

routinely performed as a screening test for congenital heart

defects in both the hospitals and data on EOS was extracted

for purpose of this study. Newborns with symptoms and

signs of sepsis prior to screening, and those admitted to the

neonatal unit were excluded.

The primary outcome was detection of hypoxemia

secondary to EOS in asymptomatic newborns. A Masimo

radical-7 pulse oximeter with a reusable probe M-LNCS

Neo was used to measure functional oxygen saturations.

The probe was secured using disposable tape to both the

right hand and either foot until a consistent reading was

obtained. The test was performed on the post-natal wards

by junior doctors and nurses within 12 hours of delivery

and again 1-2 hours before discharge after 48 hours of

postnatal life. The process of checking saturations on a

average, took less than 5 minutes The threshold values for

a positive or negative result were based on previous

reported protocol examining pulse oximetry screening in

congenital heart defects in newborns [14]. If the oxygen

saturations in both limbs were more than 94% and the

difference between the limb reading was <3%, the

newborn was deemed normoxaemic (test negative). All

test negative infants were followed up after 7 days to

identify those who developed infections or died after

discharge. If the saturations were between 90% and 94% in

either limb or the difference between the limb readings was

e”3%, the screening test was repeated 1-2 hours later.

When any reading was below 90% or the second repeat

readings remained 90 to 94% (or difference e”3%) this was

treated as positive test i.e. hypoxaemia, and the baby

underwent a clinical assessment and septic work up full

blood count, C-reactive protein, blood cultures and chest

x-ray [Figure 1]) which were performed by a pediatrician.

Any infant who had a serum CRP more than 10mg/dl or a

positive blood cultures or radiological signs of pneumonia

on the chest x-ray were considered to have early onset

sepsis.

The characteristics of the newborns were reported as

percentages. The rates of test positive newborns were

obtained as a proportion of all tested newborns. All

analyses were performed using Minitab V17. The hospital

ethics committee approved the study.

Results

During the study period, there were 213 eligible newborns

and all were screened. The clinical demographics of the

study population are shown in table 1.

Table 1: Demographic characteristics of study population

Demographic profile of patients in the study

Total Number of neonates 213

Sex distribution (M:F) 109(M):104(F)

Gestational age

35-36weeks 28 (13.1%)

36-37weeks 43 (20.1%)

37-38weeks 76 (35.6%)

38-39weeks 40 (18.7%)

39-40weeks 26 (12.2%)

Twins 6

Two of the 213 babies screened (0.93%) had a positive

pulse oximetry result. Both the infants had saturations

below 90% and were detected within 12 hours of birth.

Both were male infants and underwent a septic work up

which was consistent with sepsis. The CRP value was

>20mg/dl in both the newborns. One neonate had

radiological signs of pneumonia. Blood cultures were

negative in both the neonates but both required respiratory

support in the form of CPAP on day 2 of life. Both of them

were started on antibiotics. Follow up at one week was

completed in all the test negative newborns and none had

features of sepsis or required hospital admission.

13


Fig. 1: Study design evaluating the accuracy of pulse oximetry

in detecting early onset sepsis in asymptomatic newborns

Discussion

Our feasibility study has demonstrated that pulse oximetry

can be used as a screen for early onset sepsis in

asymptomatic newborns. None of the test negative

newborns had EOS. Our study conclusions are similar to

findings from the study done by King et al, who also

showed that pulse oximetry is a feasible tool to identify

hypoxemia associated with sepsis. However, the main

difference between our study and the study by King et al is

that all the babies in our study were routinely examined by

the paediatrician unlike King et al where only test

positives were examined by the paediatrician.

The strength of the study is that we managed to assess all

test negative newborns at one week of life and confirm that

they did not have any signs and symtoms of EOS. The main

limitation of our study is limited validation of all the test

negative newborns with a confirmatory blood test for

sepsis. Although the sensitivity and specificity of pulse

oximetry in detecting sepsis in this study is 100%, this

should be interpreted with caution because only two

newborns were test positive and also the sample size was

very small.

Worldwide, recent campaigns have concentrated on

equipping all hospitals with this potentially life-saving

equipment [18, 19]. Developing countries have mainly

prioritised the role of pulse oximetry in sick newborns, and

not as a screening tool in apparently healthy newborns.

Our study shows that using pulse oximetry for screening

for sepsis is feasible. It requires minimal training of the

hospital staff and on an average about 5 minutes to

complete the process of screening. This study may

therefore help formulating guidelines on using pulse

oximetry to rule out sepsis and form basis for future

research.

In summary, pulse oximetry may be a potential tool rule

out early onset sepsis in asymptomatic newborns. A further

study with a larger sample size is needed to confirm these

results.

References

1. Lawn JE, Cousens S, Zupan J. Neonatal Survival 1. Lancet.

2005;365:891-900.2. Polin RA. Management of neonates with suspected or

proven early-onset bacterial sepsis. Pediatrics. 2012

May;129(5):1006-153. Medline Plus. NeonatalSepsis. Accessed 19 March 2013.

A v a l a b l e : h t t p : / / w w w . n l m . n i h . g o v

/medlineplus/ency/article/007303.htm.4. Sankar MJ, Agarwal R, Deorari AK, Paul VK. Sepsis in the

newborn. Indian J Pediatr. 2008 Mar; 75(3): 261-6. 5. Edmond K, Zaidi A. New aproaches to preventing,

diagnosing and treating neonatal sepsis. PLoS Med. 2010;7.6. Concise Medical Dictionary, 8th ed. Oxford: Oxford

University Press; 2010.7. Duke T, Graham SM, Cherian MN, Ginsburg AS, English M,

Howie S, et al. Oxygen is an essential medicine: a call for

in t e rna t iona l ac t ion . In t J Tuberc Lung Dis .

2010;14(11):1362-8.8. Subhi R, Adamson M, Campbell H, Weber M, Smith K. The

prevalence of hypoxaemia amoung ill children in

developing countries: a systemic review. Lancet Infect Dis.

2009;9:219-27.9. Mwaniki MK, Nokes DJ, Ignas J, Munywoki P, Ngama M,

Newton CR, et al.Emergency triage assessment for hypoxia

in neonates and young children in a Kenyan hospital: an

observational study. Bull World Health Organisation.

2009;87:263-70.10. Duke T, Subhi R, Peel D, Frey B. Pulse oximetry:

technology to reduce child mortality in developing

countries. Ann Trop Paediatr. 2009;29:165-75.11. Thangaratinam S, Brown K, Zamora J, Khan KS, Ewer AK.

Pulse oximetry screening for critical congenital heart

defects in asymptomatic newborn babies: a systematic

review and meta-analysis. Lancet. 2012;379:2459-64.12. Richmond S, Reay G, Abu H. Routine pulse oximetry in the

asymptomtic newborn.Arch Dis Child Fetal Neonatal Ed.

2002;87:83-8.

14


13. de-Wahl Granelli A, Wennergren M, Sandberg K, Mellander

M, Bejlum C, Inganas L, et al. impact of pulse oximetry

screening on the detection of duct dependent congenital

heart disease: a Swedish prospective screening study in 39

821 newborns. BMJ. 2009;338:145-158.14. Ewer AK, Middleton LJ, Furmston AT, Bhoyar A, Daniels

JP, Thangaratinam S, et al. Pulse oximetry screening for

congenital heart defects in newborn infants ( PulseOx): a

test accuracy study. Lancet. 2011;378(9793):785-794.15. Elsa M. King, Christopher Lieu, Albion Kasasa, Andrew K.

Ewer, and Shakila Thangaratinam. Pulse Oximetry as a

Screening Tool to Detect Hypoxia Associated with Early-

onset Sepsis in Asymptomatic Newborns: A Feasibility

Study in a Low-income Country. British Journal of

Medicine & Medical Research 4(5): 1115-1128, 2014.16. Theodoratou E, Al-Jilaihawi S, Woodward F, Ferguson J,

Jhass A, Balliet M, et al. The effect of case management on

childhood pneumonia mortality in developing countries. Int

J Epidemiol. 2010;39:155-71.17. Duke T, Wandi F, Jonathan M, Matai S, Kaupa M, Saavu M,

et al. Improved oxygen systems for childhood pneumonia: a

multihospital effectiveness study in Papua New Guinea.

Lancet. 2008;372:1328-33.18. Thoms GMM, McHugh GA, O’Sullivan E. The Global

Oximetry Initiative. Anaesthesia. 2007;62:75-77.19. Lifebox, Update Tanzania. Accessed 14 April 2013.

Av a i l a b l e : h t t p : / / w w w. l i f e b o x . o r g / p r o j e c t -

updates/africa/Tanzania/.

Membership

This is to request you to encourage the paediatricians to become NNF members. For this they have to fill the membership form and send to demand draft for Rs. 10,000/- in favour of National Neonatology Forum to become a life member or pay through NEFT/RTGS. Bank detail is given below. Please download NNF membership form from NNF website www.nnfi.org

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TM


15


Abstract

Introduction

Perinatal and neonatal mortality rates are the major determinants of health care system.Every year India

1 contributes a quarter of global neonatal death and data on causes and predictors of neonatal mortality in referral tertiary units is lacking, therefore analysis of pattern of neonatal mortality is of paramount importance in formulating preventive health services.

Aim &Objectives

To find out the causes and predictors of mortality among the newborns referred to tertiary NICU.

Material and Methods:

A prospective observational study was done in Medical College, Jabalpur (March 2015 to February 2016). A total of 252 newborns were consecutively enrolled who were referred from the peripheral SNCU and admitted in outborn neonatal unit.Data was collected and statistically analysed by MS excel and SPSS 18.The critical levels of significance were considered at P<0.05.

Results

Out of 252 newborns,21.82%(n=55) died. Perinatal asphyxia 52.72%(n=29), neonatal sepsis 45.45%(n=25), SGA 38.18%(n=21), prematurity 25.45%(n=14), RDS 25.45%(n=14), MAS 20%(n=11) were the main causes of death. Very low birth weight, antenatal visits < 3, person

conducting delivery, hypothermia, respiratory distress, prolonged CRT, Spo2 <90 at the time of admission were the significant predictors of neonatal mortality. In logistic regression analysis, the significant independent predictors of mortality were person other than doctors conducting delivery, longer transport time >2 hours, low SPO & prolonged CRT at arrival and intervention (I/v 2

fluid and oxygen) not done during transport.

Conclusion

A higher fraction of neonatal deaths were associated with asphyxia and sepsis among the referred neonates suggesting inadequacies in the safe care of women during labour and effective neonatal resuscitation at peripheral health centres.A lot of modifiable risk factors are prevailing at the level of peripheral health centres that can be prevented. Early referral with proper respiratory support and thermoregulation during transport of sick neonates should keep in mind for better survival of referred neonates.

Keywords:Newborn, transport, referral, mortality predictors.

Introduction

Perinatal and neonatal mortality rates are the sensitive indicators and major determinants of quality of health care system of any country. Every year India contributes about

1quarter of global neonatal death . Neonatal death accounts for 43% of total under five child mortality, most of the newborns die in states of Uttar Pradesh, Bihar, Rajasthan and Madhya Pradesh without seeking health facilities or

.2 due to delay in health facilities To redeem this situation, in 2000, world leaders established Millennium Development Goal 4 (MDG4) for reduction of child mortality among children less than 5 years by two third of its 1990 level upto

32015 . Neonatal transport efficacy depends largely on the

Causes and Predictors of Mortality in Newborns

Referred to Tertiary Level NICU

Ghanghoriya P, Agarwal G, Barman ML, Sudhir. U

Corresponding author:Dr. Pawan GhanghoriaAssociate professor and head of the department , Department of Paediatrics,NSCB medical college, Jabalpur, M.PEmail id- [email protected]

Research Article

16


mode, adequate equipments, skilled transport team and 4effective care and communication during transport. 25-35

% mortality have been reported among the referred neonates to tertiary care centre in previous Indian literature, but it is difficult to impute the exact contribution

5-7of neonatal transport on pattern of neonatal mortality rate . In India data on the causes of neonatal mortality in referred neonates in government and private sectors is lacking and if present had shown regional variation in mortality pattern. Therefore, analysis of pattern of hospital admissions in relation to neonatal morbidity and mortality is of paramount importance in formulating preventive health services. It will also help in directing, implementing and modifying health facilities at peripheral health care unit level.

Material and methods

A prospective observational cohort study had been carried out in the out born neonatal unit of a tertiary care government hospital, Department of Pediatrics, NSCB

thmedical college, Jabalpur from 1st March 2015 to 28 February 2016. Clearance from Institutional ethical committee was taken and parents/guardian written informed consent was obtained.

A total of 252 referred neonates were consecutively enrolled based upon the inclusion criteria to our outborn neonatal intensive care unit. It includes all newborns of age <28 days referred from peripheral government special care neonatal units (SNCU and Newborns coming directly from home or some private hospital, referred from primary and secondary level health centres. Age > 28 days and Inborn newborns were excluded.

A semi structured questionnaire based detailed proforma was used to collect the data. All the newborns included in the present study were assessed for gestational age clinically by new Ballard score. Anthropometric measurements including weight, length and head circumference were measured. Details of antenatal history including maternal age, obstetric history, antenatal care visit, tetanus toxoid doses, maternal complaints like fever, p r e m a t u r e r u p t u r e o f m e m b r a n e & o t h e r obstetric/maternal illnesses were recorded. Natal history including the place of birth, attendant and mode of delivery were noted. SNCU referral notes, any premedication, presence or absence of maintenance fluid drip, oxygen delivery during transport, care of neonate during transport and mode of transport and neonatal condition on arrival were also noted. Temperature, Capillary refill time, oxygen saturation and blood glucose levels were checked and all babies were managed by using

a standard protocol.The outcome of cases was also recorded. The majority of definitions and terminologies described in study were based on national neonatal

8perinatal database working definitions (NNPD 2002-03).

The data of the study were analysed using the software MS excel and SPSS 20. Appropriate univariate and bivariate Statistical analysis were carried out using the Student’s‘t’ test for the continuous variable (age), two-tailed Fisher

2exact test or chi-square (÷ ) test for categorical variables and multivariate logistic regression analysis was done to find independent variables. To measure the linear dependence between two random variables Pearson’s correlation coefficient was used and all means were expressed as mean ± standard deviation and proportion in percentages. The critical levels of significance of the results were considered at 0.05 levels i.e. P < 0.05 was considered significant.

Results

A total of 252 consecutive neonates were enrolled in the study, of which 180 (71.42%) were males and 72(28.57%) were females.Maximum neonates were having weight (52.4%) >2500 gms, followed by 37.7% having weight 1500 to 2499 grams (LBW), 7.9% neonates were VLBW (<1500 grams.) and 2.0% neonates were ELBW (<1000 gms).

It was found that 52 % neonates who expired had weight less than 1500 gms as compared to 18.50% deaths among >1500 gms neonates and it was statistically significant (P<0.001). We found significant inverse linear trend between the neonatal deaths and birth weight of neonates admitted in our hospital (P<0.05), as the birth weight decreased higher mortality was seen among the neonates.

Figure1:Commonest causes of mortality among referred neonates.

MortalityPattern

prematurityMAS

HIE of Newborn

NeonatalSepsis

NeonatalSepsis

Smallfor date

RDS ofNewborn

17


We observed that maximum mothers (53.96 % n=136) had

ANC visits >3 as compared to mothers having 3 or less

ANC visits (46.03%, n=116). Maximum percentage of

deliveries were institutional conducted by doctors 61.9%,

followed by nurses 37.69%, others 0.4%. 40.6 % neonatal

deaths were seen in delveries conducted by others as

compared to 10.25% deaths in neonates delivered by

doctors.

Table 1: Neonatal characteristics among the expired and

surviving neonate.

Characteristics Survived Expired P value(N=197) (N=55)

Mean SD Birth 2.4721 2.2262 <0.05Weight. (0.58689) (0.7241)

Birth Weight<1500 gms. 12 13 <0.001

Preterm < 37weeks (n=56) 42 14 <0.05

Female Sex (N=72) 54 18 >0.05

Person ConductingDelivery (Othersthan doctor), (N= 96) 57 39 <0.001

Treatment Notreceived DuringTransport (N=56) 38 18 <0.05

Treatment receivedDuring Transport(N=196) 159 37 <0.05

Hypothermia atarrival (N=59) 32 27 <0.0001

prolonged CRT atarrival (N=102) 62 40 <0.0001

Spo2 <90 at arrival(N=191) 139 52 <0.0001

Hypoglycemia atarrival (N=14) 9 5 >0.05

Statistically a strong association was found in between neonatal deaths and ANC visits by mother during pregnancy (÷2 -57.36, P <0.0001), neonatal outcome and person conducting delivery (÷ 2-32.12, P<0.0001).

The most common indications for admission were

respiratory distress( 55.95%,n=141), delayed cry (46.03

%, n=116), low birth weight <1800 gms (19.44 %, n=49),

meconium aspiration (17.85%, n=45), extreme

prematurity <32 weeks (16.26 %, n=41) and refusal to feed

(13.09%, n=33) respectively.

Table 2 : Commonest causes of neonatal mortality in various

studies among referred neonates

Causes of Our Sehgal Buch Rakholia KC72 76Mortality study et al Pankaj et al agarwal

75 342016 2001 et al 2014 et al

2012 2015

Birth

asphyxia 52.72% 40% 18.8% 21.98% 27%

Neonatal

sepsis 45.45% 22.8% 16.7% 26.53% 43.66%

MAS 20% 20% 10.4% 9.18% -

RDS 25.45% 34.2% 58.3% 17.34% -

The others indication for admission were 11 cases each of

neonatal jaundice & neonatal convulsions, 4 babies with

hyperthermia, 2 neonates with congenital anomalies & 1

case each of bleeding manifestations, diarrhoea and apnea

respectively . The neonates who were in transit for long

had increasing trend of mortality as the time during

transport increases and those who were transported for

more than 120 mins had approximate thrice the rate of

neonatal death (21.99%) as compared to those who were

transported in less than 120 mins (7.93%). The outcome of

neonates referred without treatment during transport

(maintenance and oxygen) was poor and 32.14 % neonates

expired as compared to 18.87% neonatal deaths among

those who referred with the treatment during

transport(n=196) that is statistically significant (P <0.05)

At the time of admission, 23.4% were hypothermic

(<36.5°C). 5.6% were hypoglycaemic (<40 mg/dl),75.8%

were hypoxemic and 40.48%(n=102) neonates had

prolonged capillary refill time. Statistically a significant

association was found between poor neonatal outcome and

hypothermia, prolonged CRT, and hypoxemia (SPo2 < 90)

at the time of admission in our hospital (P<0.0001).

Most common causes of mortality in our setting found to

be birth asphyxia (52.72%, n=29), neonatal sepsis

(45.45%, n=25), small for date (38.18%, n=21),

prematurity (25.45%, n= 14), RDS (25.45%, n=14) and

meconium aspiration syndrome (20.00%, n=11).

In logistic regression analysis, we observed that

significant independent predictors of mortality were

person conducting delivery other than doctors, longer

transport time >120 minutes,and treatment (I/v fluid and

oxygen)not given during transport, deranged SPO <90 , 2

and prolonged CRT on arrival at tertiary centre.(Table 3)

18


Table 3: Predictors of neonatal mortality (logistic regression

analysis )

Significant Variables P value Odd’s 95%ratio of C.I. for

mortality EXP(B)

Lower Upper

Birth weight >2500 gms 0.467

Birth weight 1500-2499

grams 0.206 0.229 0.023 2.247

Birth weight 1000-1499

grams 0.197 0.220 0.022 2.192

Birth weight <1000 gms 0.534 0.464 0.041 5.213

Delivery conducted by

others 0.000 0.230 0.107 0.492

Treatment not received

during transport 0.018 0.340 0.139 0.830

Hypothermia on arrival 0.094 0.425 0.156 1.157

Prolonged CRT on

arrival 0.007 0.296 0.121 0.719

SPO2<90 on arrival 0.005 0.155 0.042 0.576

Time taken during

transport> 120 minutes 0.031 0.087 0.010 0.804

Discussion

Neonatal care is a much-required perspective in

developing nations like India in which neonatal deaths (<

28 days) contributes major part of infant mortality. In India

data on causes of neonatal morbidity and mortality in

referral neonatal units are lacking and only a few studies

had been done to know the problems of neonatal transport

and referral in India.

Overall 21.8 % neonates expired among the referred

neonates admitted in outborn NICU unit. The mortality 09 10was found similar to Kumar et al (20%), K.C Agarwal et al

and lower than the deaths in other studies focused among 6 11referred neonates by Sehgal et al (36%), Narang et al

12 13(31.66 %), Rakholia et al (25.38%), BuchPankaj et al 14 (32.2%) and Dalal et al (23.66 %) respectively. Being a

government medical college NICU this is furnished with

better intensive emergency care services, modern

equipments, trained health personnel and ready to use

neonatal protocols, which are scarce at the level of

peripheral health centres &newborn units, which might be

a reason for better survival of neonates as compared to

previous studies.

The neonatal mortality was inversely proportional to birth 11 weight & gestational age among the referred neonates.

More deaths among extremely low birth weight neonates 11 were observed in various Indian studies by Narang et al

13 6BuchPankaj et al , Sehgal et al . Similarly we observed a

significant linear increasing trend in mortality, as the

weight of neonate decreases.

Almost 53.98 % of mother had 4 or more antenatal visits in

the study group. Data collected from previous literature in

developing countries shows similarity that 95% deliveries 15 being conducted at health care facility but studies by

11 6 Narang et al and Sehgal et al showed that 75.6% and

55.8% of deliveries were institutional, so there has been a

significant increase in institutional deliveries over a

decade. Poor antenatal check-up by mother increases the

risk of neonatal deaths as opportunity of consultation

regarding heal th and detect ion of ear ly r isk

factors/complications is missed. In our study group, we

found higher deaths among the neonates delivered by other

than doctors that is comparable with observation of 13 14BuchPankaj et al and Dalal et al .The deliveries

conducted by untrained birth attendants also contribute to

higher rate of newborn deaths due to lack of proper skill in

managing the deliveries properly.

In developing countries pre-referral stabilization and

appropriate care during transport by a trained person may

even be Asha/anganwadi worker might lead to better 16 outcome of neonates among referred neonates. In our

study we observed that the neonates which were stabilized

by treatment with i.v fluids and oxygen (77.77%) before

and during transport had significantly lower deaths

(18.87%) than the babies who were not managed properly

during transport (32.14% ). It was found earlier also that

there was a significant decrease in neonatal mortality

where interventions like administration of intravenous

fluid, provision of warmth and/or oxygen administration 11was done just before transportation.

The neonates who were transported for more than 120

minutes had increasing trend of mortality and had thrice

the rate of neonatal death (22.59%) as compared to those

who reached in 120 minutes. A previous study by revealed

that the birth weight <1 kg and time taken > 1hour to be

significantly associated with mortality of transported

neonates. 11 The findings in our study were found little bit 17comparable with the findings of Mori et al in which

neonates which were transported for more than 90 mins

had more than twice of neonatal death as compared with

those who were transported in <60 mins.

19


We observed that at the time of arrival 23.4% neonates had

hypothermia, 40.48% neonates had prolonged CRT,

72.2% neonates had respiratory distress and 75.8%

neonates had SPO2 <90. The survival of these neonates

with deranged physiological status at the time of arrival

was poor and 45.76% were expired among hypothermic

newborns, 39.21% among abnormal CRT, 30.22% among

newborns with respiratory distress, 27.22% among

newborns with low SPO2. Suboptimal condition of

neonatal thermoregulation during transfer were 18 immediately associated with poor neonatal outcome. The

role of presence of hypoglycaemia and hypothermia at the

time of admission in neonatal deaths among referred

newborns were found in considerable number and 19 discussed in various studies. Our study also reported a

significant proportion of hypothermia among the referred

neonates that is comparable with observations by KC 10 13 11Agarwal et al ,BuchPankaj et al &Narang et al , but it

could not find any significant relationship with

hypoglycaemia .The presence of severe hypothermia,

severe respiratory distress and poor perfusion on 6,13admission leads to higher neonatal deaths corroborated

20 our findings. Tinuade et al also found higher mortality

among hypothermic newborns with respiratory distress.

The babies with the unstable status at peripheral point

might have similar deranged status at the arrival in tertiary 21centres , thus emphasize and focus on prior stabilization

should be kept in a view. In our study we found that low

SPO and respiratory distress at the time of admission were 2

signif icantly associated with neonatal deaths.

Maintaining and ensuring vital parameters with pulse

oximetry before and during transport from referred point is

helpful and probably least practiced in management of

neonatal health in our country.

The most common causes for neonatal mortality were

Birth asphyxia (52.72 %), neonatal sepsis(45.45%), small

for date (38.18%),prematurity (25.45 %), RDS (25.45%)

and MAS (20 %).{figure 1}

The main causes of neonatal mortality in these studies

were found similar to our study, but the causes of neonatal

deaths due to birth asphyxia and sepsis were found higher

& neonatal deaths due to sepsis (45.45%) were found 10comparable with results of KCAgarwal et al (43.66%)

among the referred neonates.The causes of neonatal

morbidity and mortality due to meconium aspiration

syndrome (MAS) were found comparable to results of 6Sehgal et al . (Table 3).The neonatal admissions and deaths

due to respiratory distress syndrome(RDS) were found

6,13 .less in our study as compare to previous studies The

known predisposing factors for neonatal infections are

unhygienic & un-sterile delivery practices in resource

poor settings and unhygienic transport of sick newborn. A

higher proportion of neonatal admissions and deaths were

associated with birth asphyxia among the referred

neonates suggesting inadequacies in the care of women

during labour and effective neonatal resuscitation.

The main predictors of poor neonatal outcome found in

univariate analysis were derangements on arrival such as

hypothermia, respiratory distress and prolonged CRT, low

SPO2, prolonged neonatal transport, and very low birth

weight. Predictors of mortality in our study were similar to

those reported earlier from the studies among referred 6 11neonates in tertiary centres by Sehgal et al &Narang et al ,

but hypoglycemia and maturity were not found similar to

these studies in predicting mortality.To look for

confounding factors found to be significant on univariate

analysis they were kept into a logistic regression model.

The significant independent predictors of mortality were

person conducting delivery other than doctors, longer

transport time >120 minutes, low SP02 at the time of

arrival, prolonged CRT on arrival, treatment not received

during transport.

Conclusion

A higher fraction of neonatal deaths was associated with

asphyxia and sepsis among the referred neonates

suggesting inadequacies in the care of women during

labour and lack of effective neonatal resuscitation at

peripheral health centres.A higher proportion of neonatal

deaths were seen among those who were not treated

properly during transport, this predisposed them to

Hypoglycemia and shock, a reason behind the poor

outcome among referred neonates.Very low birth weight

infants, infants delivered by others than doctors,

prolonged transport time, lack of in transport treatment

and deranged physiological status (respiratory distress,

poor perfusion, low spo2, hypothermia) at arrival have

higher chances of mortality. So, there was a lack of early

identification of sick neonates, their timely referral and

transport without time delay.

A lot of modifiable risk factors are prevailing at the level of

peripheral health centres like poor health education to

mothers regarding antenatal care, improper resuscitation

techniques, unsterile delivery care, delay in evaluation and

identification of sick new-born, delay in referral ,improper

20


communication with higher tertiary centres, poor parental

counselling & advice regarding care during transport, poor

management during transport .These factors are obstacles

in paving path for a better neonatal health, better efforts

should be done at peripheral health centres to abolish

these factors prevailing at the level of centres.

Our study highlights the need of Antenatal and intrapartum

monitoring of high risk pregnancies, effective

resuscitation by trained health personnel at the time of

birth in a neonatal resuscitation corner & skill upgradation

of peripheral health workers in resuscitation (Basic NRP)

should be made compulsory to reduce the high morbidity

& mortality related to birth asphyxia. A protocol for

neonatal transport should be made at all peripheral SNCUs

and effective implementation of these protocols during

transport should be ensured. The neonatal transport should

be upgraded with well-equipped ambulances, modern

equipments, trained accompanying health personnel, prior

communication, family counselling, proper care with

maintenance of thermoregulation and respiratory support

as well as feedback from referring unit should be kept in a

view for better survival of neonates. Maintaining and

ensuring vital parameters (temperature, capillary,

perfusion and sugar), pulse oximetry before and during

transport from referred point is recommended, to provide

them an objective & more reliable tool. There is also a need

of strengthening of tertiary care centres with the adequate

life savingequipments and sufficient number of trained

health staff as per the workload to prevent high mortality

among very low birth weight babies and to provide best

possible care required for sick babies.

References

1. Lawn JE, Kinney MV, Black RE, Pitt C, Cousens S, Kerber

K, Corbett E, Moran AC, Morrissey CS, Oestergaard MZ.

Newborn survival: a multi-country analysis of a decade of

change. Health policy and planning. 2012 Jul 1;27(suppl

3):iii6-28

2. Darmstadt GL, Oot DA, Lawn JE. Newborn survival:

changing the trajectory over the next decade. Health policy

and planning. 2012 Jul 1;27(suppl 3): iii1-5)

3. Indicators for Monitoring the Millennium Development

Goals. United Nations. New York: United Nations

Publication. 2003 Sept;31-33.

4. ( h t t p : / / w w w. i n . u n d p . o rg / . . . m d g s / i n d i c a t o r s - f o r -

monitoring-the-millennium-development-goals)

5. Babinard J, Roberts P. Maternal and child developmental

goals: What can transport sector do? The World Bank group

Transport paper. Available from:http://www.siteresources.

orldbank.org/inttransport/tp12_maternal_helath.pdf.

[Accessed on 2011 Apr 21].

6. Singh H, Singh D, Jain BK. Transport of referred sick

neonates: How far from ideal? Indian Pediatr 1996;33:851-

3.

7. Sehgal A, Roy MS, Dubey NK, Jyothi MC. Factors

contributing to outcome in newborns delivered out of

hospital and referred to a teaching institution. Indian Pediatr

2001;38:1289-94.

8. Basu S, Rathore P, Bhatia BD. Predictors of mortality in very

low birth weight neonates in India. Singapore Med J

2008;49:556-60.

9. NNPD working definitions. NNPD report 2002-03. NNPD

network, ICMR; p 62-70.

10. Kumar M, Paul VK, Kapoor SK, Anand K, Deorari AK.

Neonatal outcomes at a sub district hospital in north India.

Journal of tropical pediatrics. 2002 Feb 1;48(1):43-6.

11. Aggarwal KC, Gupta R, Sharma S, Sehgal R, Roy MP.

Mortality in newborns referred to tertiary hospital: An

introspection. Journal of family medicine and primary care.

2015 Jul;4(3):435.

12. Narang M, Kaushik JS, Sharma AK, Faridi MM. Predictors

of mortality among the neonates transported to referral

centre in Delhi, India. Indian journal of public health. 2013

Apr 1;57(2):100.

13. Rakholia R, Rawat V, Bano M, Singh G. Neonatal morbidity

and mortality of sick newborns admitted in a teaching

hospital of Uttarakhand. CHRISMED Journal of Health and

Research. 2014 Oct 1;1(4):228.

14. BuchPankaj M, MakwanaAarti M, Chudasama Rajesh K,

DoshiSmita K. Status of Newborn Transport in Periphery

and Risk Factors of Neonatal Mortality among Referred

newborns. Journal of Pharmaceutical and Biomedical

Sciences. 2012;16(09):3.

15. Dalal E, Vishal G, Solanki D. Study on neonatal transport at

tertiary care centre. hospital. 2013;84(28):49.

16. Hoque M, Haaq S, Islam R. Causes of neonatal admissions

and deaths at a rural hospital in KwaZulu-Natal, South

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Infection. 2011 Jan 1;26(1):26-9.

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images/pdf/nnf_cpg_consolidated_file-january102011

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Negishi H, Doyle P. Duration of inter facility neonatal

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Pretz D, Carmona D, López TS, Fariña D. Risk factors

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Registration and Formation Guidelines for NNF State Chapter• The geographical area & nomenclature of the state should be well define

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2. A minimum of 10 life members are requested to constitute the General Body of the State/Regional/City chapter. Once a state/regional/City chapter is established the Governing Body must be formally approached by its office bearers to seek official recognition.

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5. “Finances”: All branches will be allowed to raise funds by way of subscription, advertisement, registration fee for program permissible under ethical code for their activities.

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8. The General Body of the NNF shall be the final arbiter of any dispute between the State Chapters and the NNF. The decision of the General Body shall be final and binding.

9. The directive principles guiding the activities of the State/Regional/City Chapters shall be communicated by the President/Secretary NNF from time to time.

Dr. B. D. Bhatia Dr. Ajay Gambhir Dr. Alok Bhandari Dr. Lalan K. BhartiPresident Imm. Past President Secretary Jt. Secy. cum Treasurer

TM


22


Abstract

High flow nasal canula support has gained importance as a

form of non-invasive ventilation support in premature

i n f a n t s w i t h r e s p i r a t o r y d i s t r e s s s y n d r o m e ,

postextubation, apnea of prematurity and in weaning from

CPAP. The ease of its use and the reduced risk of nasal

trauma over NCPAP has compelled clinicians to use it

increasingly, despite lack of strong evidence. It is shown

to be useful in term and preterms both, but, more RCTs are

needed to prove its efficacy in extreme preterms

(<28weeks).

Introduction

HHHFNC is heated, humidified high flow nasal cannula.

Flow rates of more than one-liter per minute of air or

blended oxygen cum air have been used to described as

high flow[1], which are delivered through thin and tapered

nasal cannulae after heating and humidification.

Vapotherm, RAM’s cannula and Optiflow are commonly

used HHHFNC devices for administering high flow. The

ease of its use and reduced risk of nasal injury has led to

it’susagewidely. However, there is an uneasy question on

the amount of generated ‘distending pressure’ by

HHHFNC,which is not easy to answer. The clinical utility

of this form of support was seen initially primarily in

infants with Bronchiolitis[1,2], and now it has been tried in

neonates ,especially in premature infants with Respiratory

Distress Syndrome as primary modality, post-extubation,

for apnea of prematurity and as a weaning modality from

CPAP[3].

Definition of flow in HHHFNC

The flow rates are widely variable with the infant

population and currently there is no single agreed

definition for ‘high flow’. Flow of more than 1 liter per

min was used as definition of high flow in preterm infants

in Cochrane review [1]. In infants older than 4 weeks, flow

of >2Litre/min was used to define high flow [4]. A recent

meta-analysis used >2L/min of flow to define ‘High Flow

therapy’[5]. The flow is considered as ‘high’ if it exceeds

the infant’s inspiratory flow demand and facilitates

purging of the oro-naso-pharyngeal dead space. Few

authors adjust flows based on the respiratory mechanics

and recommend a flow of 2Litres/kg/min to provide an

optimal distending pressure and reduced work of

breathing [6, 7]. Although the definition of high flow is

more than 1-2L/min, many recent studies have used flow

of 5-8L/min for infants on HHHFNC support and this flow

is now the standard of practice [5, 8].

Distending pressure in HHHFNC

The generated pressure in HHHFNC depends on various

factors like birth weight, gestation, flow rates, nasal prong

size, site of pressure measured (oral/ pharyngeal/

esophageal) and mouth leak (open vs closed). Pressure in

HHHFNC increases with increasing flow rate [9], higher

prong size [10], decreasing gestation/weight [9] and with

mouth closed [10]. Few authors have raised concerns of

uncertain pressures and pulmonary over distension/air

leaks [10,11]. Wilkinson et al derived a formula to

calculate the pressures after studying 18 premature infants

[pharyngeal pressure (cm H O)=2.6+0.8 F”1.4 wt. 2

High Flow Nasal Canula Therapy (HHHFNC)

in Neonates –Will it Replace CPAP?

Abdul Razak, N Karthik Nagesh


Prof. N Karthik Nagesh,

Chairman-HOD of Neonatology & MACC,

Manipal Advanced Children’s Centre(MACC),

Manipal Hospitals, Bangalore, India


[email protected]


23


”1(F=flow in l min , wt=weight in kg) & Predicted pressure ”1(cm water)=0.7+1.1 × F (F=flow per weight in l min

”1kg )]. Similarly, a recent study performed by Iyer et al

found the correlation between the flows and generated

esophageal pressures and derived the formula to calculate

the end-expiratory esophageal pressure [pressure (cm

H O) = 1.18 x HFNC (L/min)] in preterm infants[12]. On 2

the contrary, Sreenan et al predicts comparable pressure of

6 cm H 2 O with a flow of 1.6 L/min in a one-kg infant [13].

Locke et al showed the effect of nasal cannula size on

generation of distending pressures; flow of 2L/min in an

infant on HHHFNC with 2cm size prongs did not generate

significant esophageal pressures, however using higher

sized prongs of 3 cm size produced pressures of 9.8

cmH2O in the same infant with comparable flows ([10,11].

Sivieri et al showed in his in vitro study the effect of

cannula size on the pressure generated; the nasal prong-to-

nares ratio of >0.9 would produce pressure of 18 cm H2O

even if 50% of mouth leak is present compared to pressures

of <10 cm H20 if the nasal prong-to-nares ratio is <0.9 and

mouth is closed[14]. The predicted pressures in the

aforementioned studies are surprising and very discrepant.

Clinicians should hence, carefully choose the appropriate

s ized prongs and f lows based on the infant

weight/gestation. In HHHFNC therapy hence, the

suggested prong size is half that of the nostril (nasal prong-

to-nares ratio=0.5) [14].

Mechanism of gas exchange with HHHFNC

The effect of HHHFNC on respiratory mechanics is

mainly through flow-pressure effect and gas conditioning.

1. Flow-Pressure effect-Pressure in HHHFNC is flow driven which in turn reduces the work of breathing by preventing pharyngeal collapse and providing positive distending pressure which stents the small airway [6, 15].

2. Flow effect-

a) The high flow will augment the inspiratory flows of the patient and attenuates the resistance contributed by the retraction of nasopharyngeal mucosal walls and thereby reducing the resistive work of breathing. This effect is independent from the CPAP effect which is shown by the work by Saslow et al [16]. He showed that the work of breathing was equivalent with CPAP at 6 cm H2O versus high flow 3-5L/min despite a significant lower esophageal pressures. The inspiratory flow is believed to split into a major portion ,which

enters the trachea, and a small portion of gas exiting through the mouth. In expiration, the tracheal expired gas separates the gas flow from posterior wall of nasopharynx by disrupting the boundary layer and thereby potentially assisting the infant into expiration resembling “Coanda effect” of the Infant flow driver CPAP[17].

b) The ‘High flow’ washes out the ‘end expiratory’

oxygen depleted gases which in turn helps in

delivery of oxygen rich gas and reduces carbon-

dioxide rebreathing in subsequent breaths [18].

This clearance effect is proportional to the extra

thoracic dead space which is 2-3times greater in

children than adults [19]. This space measures 3

mL/kg in newborns reaching to adult level of

0.8ml/kg by 6 years [19].

3. Conditioning of gases-Heating of gases between 34-o37 C and humidifying them to 100% reduces the

airway resistance, improves mucociliary clearance

and reduces heat/energy expenditure on heating-

humidifying the gas by the infant [6, 17, 20]. A neonate

weighing 3 kg will spend 26 kilocalories per minute

for conditioning the gas if the inspired ambient air otemperature is 21 C and relative humidity is 50%,

considering the tidal volume is 18ml and the neonate is

breathing at 60/min. The formula to calculate energy

requirement for gas conditioning is ETotal/L= Eg(37-

Tamb)+ Evap(44mg-AHamb)[17].

HHHFNC in preterms with RDS as a ‘primary mode

There is paucity of strong literature in this regard. There is

considerable lack of evidence on HHHFNC as a primary

mode of CPAP. Few randomized trials have been

performed in neonates with mild to moderate/stable RDS.

Apart from these, there were observational studies which

looked into mild RDS. Saslow et al found no difference in

VtusingNCPAP or HHHFNC in stable neonates with mild

RDS [16]. In a retrospective study performed by

Shoemaker et al, there was no difference found in

outcomes like death and BPD, however patient ventilation

days were reduced in neonates on HHHFNC f used as an

early mode of respiratory support compared to NCPAP

[21, 22]. Lampland et al found no difference in end-

expiratory esophageal pressure with both devices (NCPAP

vs HHHFNC), however neonates developed tachypnea

once flow is diminished [21]. A RCT on 67 neonates

performed by Nair and Karna showed no difference in any

outcomes; this study was however ceased early due to

24


recall of the ‘Vapothermcircuits’[3]. A recent randomized

cross-over trial performed by Lavizzari et al comparing

HHHFNC with CPAP in 20 preterm infants with mild-

moderate RDS found no difference in lung mechanics,

work of breathing and gas exchange. A recent meta-

analysis has supported the use of HHHFNC as it appeared

safe and efficacious similar to other modes of non-

invasive ventilation as a ‘primary support’ or ‘after

extubation’[5]. But, in the absence of strong evidence,

HHHFNC cannot be recommended as a primary modality

in neonates with severe RDS. The use of HHHFNC as a

primary modality of respiratory support in neonates with

mild to moderate RDS is justified in moderate to late

preterms. However, caution needs to be exercised in

extremely preterm infants less than 28 weeks gestation.

HHHFNC in ‘apnea of prematurity’ (AOP)

The role of HHHFNC in AOP is unclear. The only

randomized trial available where the primary objective to

assess the role of HHHFNC in AOP was performed by

Sreenan et al in 2001[13]. The author found HHHFNC as

effective as NCPAP in management of AOP. There was no

further research performed to evaluate the role of

HHHFNC in AOP; hence to recommend its use in AOP is

still unclear.

HHHFNC in ‘post-extubation setting in preterms’

Despite strong evidence on CPAP to prevent extubation

failure [23], HHHFNC is now being practised at many

centers in the post-extubation period. The initial RCT

p e r f o r m e d b y C a m p b e l l e t a l f o u n d h i g h e r

treatment/postextubation failure rates in HHHFNC

compared to NCPAP group [24]. The failure could have

been because of lower flows in this study compared to the

current flows used in clinical studies; flows were derived

from formula of Sreenan et al[13], which ranged from 1.4-

1.7L/min. Shoemaker et al in his retrospective study also

found the higher failure rates in HHHFNC compared to

NCPAP group[22]. The later RCTs on HHHFNC

comparing the NCPAP showed promising results. Collins

et al found similar rates of extubation failure between the

HHHFNC and NCPAP, however, there was lowered nasal

trauma score in HHHFNC group (3.1) compared to

NCPAP group (11.8) [25]. A similar study by Yoder et al

found no difference in outcomes between HHHFNC and

NCPAP for primary therapy in respiratory dysfunction or

postextubation[25, 26]. A multicenter non-inferiority trial

performed by Manley et al in very preterm neonates found

the efficacy of HHHFNC similar to NCPAP in preventing

extubation failure [8]. The pressures in NCPAP group was

7 cm of H20 and the flow in HHHFNC group was 5-

6L/min. There was 34.2% and 25.8% treatment failure in

HHHFNC and NCPAP groups respectively. This study

also showed significant lower nasal trauma in HHHFNC

group. A similar multicentric study by a collaborative

group on HHHFNC in 2012-13 included 255 preterm

neonates found no difference in any outcomes between

HHHFNC and NCPAP group [27]. There was no

statistically significant differences between rates of

extubation failure, air leaks and Bronchopulmonary

dysplasia. A recent meta-analysis on HHHFNC showed

high flow therapy to be similar in terms of safety and

efficacy compared to NCPAP or other modes of non-

invasive ventilation [5]. Although, HHHFNC has not

become standard of practice after post-extubation; many

centers are now practising it as a mode to prevent

extubation failures over NCPAP because of lowered nasal

trauma score and better comfort score.

HHHFNC as a ‘weaning mode from CPAP’

Growing use of HHHFNC in mild-moderate RDS has led

clinicians to assume its standpoint in weaning from the

CPAP support. The postulation of this strategy is based on

assumption of equivalent CPAP effect and meriting

comfort score with lowered nasal trauma. To evaluate this

strategy many authors have conducted few studies to find

the role of HHHFNC as a weaning mode from CPAP. The

first trial was performed by Abdel-Hady et al and he

randomized 60 preterm infants who were on NCPAP for

more than 24 hours to continued NCPAP or to HHHFNC at

2L/min. HHHFNC group neonates were weaned first on

oxygen to room air followed by flow at a rate of 0.5

L/min/6hrs. He found the duration of respiratory support

(18 vs. 10.5 days; p = 0.03) and oxygen use (median 14 vs.

5 days; p < 0.001) was significantly higher in HHHFNC

group. A similar trial was performed by Iranpour et al

where preterm neonates were randomized into HHHFNC

and continued NCPAP support. The flows in this study

were calculated from the formula by Sreenan et al. He

found no difference in any outcomes. Fernandez et al

conducted a study where neonates were randomized into

combination of NCPAP with HHHFNC versus NCPAP

with Low flow nasal cannula and found 50% reduction in

NCPAP days with HHHFNC. A retrospective analysis by

Sasi et al found minimal effect on CLD rates with use of

HHHFNC as weaning mode from NCPAP. A recent

randomized trial by Tang et al from a single center where

the preterm infants were randomized into four arms:

25


abrupt wean with HHHFNC, abrupt wean without

HHHFNC, gradual wean with HHHFNC and gradual wean

without HHHFNC. The authors found no difference in any

outcome, however abrupt weaning with HHHFNC has

shown significant reduction in NCPAP days but did not

reduce the duration of respiratory support. It is convincing

from the above studies that HHHFNC could be used as a

weaning mode from NCPAP to avoid the risk of nasal

injury.

HHHFNC use- guidelines

High flow support is an amiable form of non-invasive

respiratory support. The current literature provides a

definite and strong evidence of reduced nasal injury over

NCPAP [5, 8]. Calculation of pressures from flow based

formulas from the remote studies [13] led to

overestimation of pressures and low flows resulted in poor

yield. The recent studies[12] to calculate pressures are

logical and applying 5 to 8 L/min of flows provide

distending pressures of 5-8cm of H2O if appropriately

chosen nasal prong size(nasal prong-to-nares ratio=0.5) is

used and neonate’s mouth is kept open. Prongs are to be oabout 50% of nostril diameter. Gas is to be heated to 37 C

and 100% humidity. Flow is kept 3 to 8 L/min for neonates.

The baby’s Mouth not actively closed. Blended

Oxygen+Air is given to achieve appropriate SpO . 2.

Weaning of first the FiO & then the flow rate is done.When 2

flow is <2 L/min consider stopping HHHFNC.

HHHFNC- is it the way ahead?

HHHFNC appears safe to use as a primary mode in

moderate to late premature infants with mild to moderate

respiratory disease, post extubation and in weaning from

NCPAP. However, caution needs to be exercised in very

premature infants and in unstable infants. HHHFNC is

emerging as an equivalent modality of non invasive

ventilation in babies with respiratory distress and post

extubation.Failure criteria are same as for CPAP. It is

shown to be useful in term and preterms both, more RCTs

are needed to prove its efficacy in extermepreterms

(<28weeks).It’s baby friendliness is leading to be used as

a first mode of NIV in RDS.

References

1. Wilkinson D, Andersen C, O’Donnell CP, De Paoli AG.

High flow nasal cannula for respiratory support in preterm

infants. Cochrane Database Syst Rev. 2011; CD006405.

2. McKiernan C, Chua LC, Visintainer PF, Allen H. High flow

nasal cannulae therapy in infants with bronchiolitis. J

Pediatr. 2010;156: 634–638.

3. Manley BJ, Dold SK, Davis PG, Roehr CC. High-flow nasal

cannulae for respiratory support of preterm infants: a review

of the evidence. Neonatology. 2012;102: 300–308.

4. Mayfield S, Jauncey-Cooke J, Hough JL, Schibler A,

Gibbons K, Bogossian F. High-flow nasal cannula therapy

for respiratory support in children. Cochrane Database Syst

Rev. 2014;3: CD009850.

5. Kotecha SJ, Adappa R, Gupta N, Watkins WJ, Kotecha S,

Chakraborty M. Safety and Efficacy of High-Flow Nasal

Cannula Therapy in Preterm Infants: A Meta-analysis.

Pediatrics. 2015;136: 542–553.

6. Milési C, Baleine J, Matecki S, Durand S, Combes C, Novais

ARB, et al. Is treatment with a high flow nasal cannula

effective in acute viral bronchiolitis? A physiologic study.

Intensive Care Med. 2013;39: 1088–1094.

7. Mayfield S, Bogossian F, O’Malley L, Schibler A. High-

flow nasal cannula oxygen therapy for infants with

bronchiolitis: pilot study. J Pediatrics ChildHealth.

2014;50: 373–378.

8. Manley BJ, Owen LS, Doyle LW, Andersen CC, Cartwright

DW, Pritchard MA, et al. High-flow nasal cannulae in very

preterm infants after extubation. N Engl J Med. 2013;369:

1425–1433.

9. Wilkinson DJ, Andersen CC, Smith K, Holberton J.

Pharyngeal pressure with high-flow nasal cannulae in

premature infants. J Perinatol. 2008;28: 42–47.

10. Hasan RA, Habib RH. Effects of flow rate and airleak at the

nares and mouth opening on positive distending pressure

delivery using commercially available high-flow nasal

cannula systems: a lung model study. PediatrCrit Care Med.

2011;12: e29–33.

11. Locke RG, Wolfson MR, Shaffer TH, Rubenstein SD,

Greenspan JS. Inadvertent administration of positive end-

distending pressure during nasal cannula flow. Pediatrics.

1993;91: 135–138.

12. Iyer NP, Mhanna MJ. Association Between High-Flow

Nasal Cannula and End-Expiratory Esophageal Pressures in

P r e m a t u r e I n f a n t s . R e s p i r C a r e . 2 0 1 5 ;

doi:10.4187/respcare.04317

13. Sreenan C, Lemke RP, Hudson-Mason A, Osiovich H. High-

flow nasal cannulae in the management of apnea of

prematurity: a comparison with conventional nasal

continuous positive airway pressure. Pediatrics. 2001;107:

1081–1083.

14. Sivieri EM, Gerdes JS, Abbasi S. Effect of HFNC flow rate,

cannula size, and nares diameter on generated airway

pressures: an in vitro study. PediatrPulmonol. 2013;48:

506–514.

15. Spentzas T, Minarik M, Patters AB, Vinson B, Stidham G.

Children with respiratory distress treated with high-flow

nasal cannula. J Intensive Care Med. 2009;24: 323–328.

16. Saslow JG, Aghai ZH, Nakhla TA, Hart JJ, Lawrysh R, Stahl

GE, et al. Work of breathing using high-flow nasal cannula

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in preterm infants. J Perinatol. 2006;26: 476–480.

17. Dysart K, Miller TL, Wolfson MR, Shaffer TH. Research in

high flow therapy: mechanisms of action. Respir Med.

2009;103: 1400–1405.

18. Roca O, Riera J, Torres F, Masclans JR. High-flow oxygen

therapy in acute respiratory failure. Respir Care. 2010;55:

408–413.

19. Numa AH, Newth CJ. Anatomic dead space in infants and

children. J Appl Physiol. 1996;80: 1485–1489.

20. Milési C, Boubal M, Jacquot A, Baleine J, Durand S, Odena

MP, et al. High-flow nasal cannula: recommendations for

daily practice in pediatrics. Ann Intensive Care. 2014;4: 29.

21. Lampland AL, Plumm B, Meyers PA, Worwa CT, Mammel

MC. Observational study of humidified high-flow nasal

cannula compared with nasal continuous positive airway

pressure. J Pediatr. 2009;154: 177–182.

22. Shoemaker MT, Pierce MR, Yoder BA, DiGeronimo RJ.

High flow nasal cannula versus nasal CPAP for neonatal

respiratory disease: a retrospective study. J Perinatol.

2007;27: 85–91.

23. Davis PG, Henderson-Smart DJ. Nasal continuous positive

airways pressure immediately after extubation for

preventing morbidity in preterm infants. Cochrane

Database Syst Rev. 2003; CD000143.

24. Campbell DM, Shah PS, Shah V, Kelly EN. Nasal

continuous positive airway pressure from high flow cannula

versus Infant Flow for preterm infants. J Perinatol. 2006;26:

546–549.

25. Collins CL, Holberton JR, Barfield C, Davis PG. A

randomized controlled trial to compare heated humidified

high-flow nasal cannulae with nasal continuous positive

airway pressure postextubation in premature infants. J

Pediatr. 2013;162: 949–54.e1.

26. Yoder BA, Stoddard RA, Li M, King J, Dirnberger DR,

Abbasi S. Heated, humidified high-flow nasal cannula

versus nasal CPAP for respiratory support in neonates.

Pediatrics. 2013;131: e1482–90.

27. Collaborative Group for the Multicenter Study on Heated

Humidified High-flow Nasal Cannula Ventilation.

[Efficacy and safety of heated humidified high-flow nasal

cannula for prevention of extubation failure in neonates].

ZhonghuaErKeZaZhi. 2014;52: 271–276.

Announcement NNF Training Fellowship for Doctors and Nurses

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27


Introduction

Respiratory distress is one of the commonest reasons for

admission to a neonatal unit.

(1)

(2)

CPAP for RDS

In the year 2006, we started using CPAP as a primary

respiratory support for preterm infants with respiratory

distress, recurrent apneas and as a post extubation strategy.

We started with 2 bubble-CPAP machines (Fisher and

Paykel), disposable circuits and bi-nasal prongs (Fisher

and Paykel). With the experience on few neonates, to

rationalize the protocol for application and monitoring, we

In India, nearly 26 million

infants are born every year. Assuming 10 % incidence of

respiratory distress in newborn infants, nearly 2.6 million

infants are in need of oxygen or CPAP for respiratory

distress. Assuming 20 % of infants with oxygen need

may require non-invasive respiratory support (CPAP) for

respiratory distress , nearly 5 lakhs (0.5 million) infants

per annum require CPAP as a mode of respiratory support

in our country. As most of these infants either die or are

referred to tertiary care facilities, CPAP would play a

major role in preventing the neonatal deaths in preterm

infants and also in decreasing the up-transfers. Our

journey of CPAP usage at Fernandez hospital started in the

year 2006 with 2 bubble CPAP machines. In this review we

would elaborate on the progress of CPAP usage in our unit

over the last decade.

looked at the risk factors for failure and published this

experience in the year 2008-09. We evaluated the

immediate outcomes of 56 preterm infants with

respiratory distress syndrome (RDS) on Bubble CPAP and

identified the risk factors associated with its failure (April

2007 to May 2008).(3)All admitted consecutively born

preterm infants with gestation between 28 to 34 weeks,

with respiratory distress and chest X-ray suggestive of

respiratory distress syndrome (RDS) were evaluated.

Eligible infants were started on Bubble CPAP with bi-

nasal prongs (Fisher and Paykel Healthcare, New

Zealand). PEEP was started at 5 cm of water and adjusted

to minimize chest retractions. FiO2 was adjusted to

maintain SpO2 between 87% and 95%. Flow was titrated

to the minimum to produce continuous bubbling in the

bubble chamber. Surfactant was administered by InSurE

technique and was given to babies with moderate or severe

RDS on the chest X-ray and or FiO2 requirement >30%.

Infants were diagnosed to have failed on CPAP and started

on mechanical ventilation within the first 7 days after birth

when they: (a) remained hypoxic, i.e. SpO2<87% despite

FiO2>70% and PEEP >7cm of water; (b) had severe

retractions on PEEP >7cm of water; (c) had prolonged

(>20 seconds) or recurrent apneas (d) had severe

metabolic acidosis or shock requiring inotropic support

>20ìg/kg/min. The mean gestation was 30.98±2 weeks and

mean birthweight was 1387 ± 402 grams among the

enrolled infants. Nearly 80% of the infants were complete

steroid covered. The median age of starting CPAP was 1.7

hours of life. Thirty one infants (55.4%) received

surfactant and the median age of surfactant administration

was 3 hrs (range 1 hr to 15 hrs of life). None of the surviving

infants had bronchopulmonary dysplasia (BPD) or

retinopathy of prematurity (ROP) requiring laser.

CPAP for Respiratory Distress in Newborns:

A Decade of Experience

Srinivas Murki, Hemasree Kandraju,

Tejo Pratap Oleti, Anupama, Pramod Gaddam

Corrresponding author:

SrinivasMurki

Consultant Neonatologist

Fernandez hospital

Hyderguda, Hyderabad

Email: [email protected]


28


Fourteen (25%) babies failed CPAP. The variables

associated with failure of CPAP were: no or only partial

exposure to antenatal steroids (RR 3, 95% CI 1.2 - 7.8),

whiteout appearance on the chest X-ray (RR 3.9, 95% CI

1.8-8.4), patent ductusarteriosus (RR 3, 95% CI 1.02-8.8),

sepsis/pneumonia (RR 7.5, 95% CI 1.6- 34) and Downe’s

score >7 or FiO2 e”50% after 15 to 20 minutes of CPAP

(RR 1.6, 95% CI 1.1-2.6). The mortality rate was 10.7% (6

of 56). From this experience of 25% CPAP failure in

preterm infants with RDS, we hypothesized that moderate-

sized preterm infants (gestation28 to 33weeks) with RDS

on nCPAP would have lesser need for MV in the first 7 days

of life, when treated with surfactant within the first 2 h of

life, compared to thosetreated late (after 2 h and with a FiO 2need > 0.50).

In another study (April 2008 to May 2011) we enrolled 153

infants with RDS on chest x-ray and randomized 74 infants

to early surfactant group and 79 infants to late surfactant

group. (4) Eligible infants received CPAP with a bubble

CPAP generator (Fisher and Paykel Healthcare, Inc.) using

short binasal prongs (Hudson). Initial CPAP pressure was

5 cm of H2O. The median gestation was 30 weeks and the

median birth weight was 1250 grams in the enrolled

infants. The median time for starting CPAP was similar in

the two groups [47 min, IQR 33–60, vs. 45 min, IQR

30–60]. Forty-four infants (55.7%) in the late group did

not receive any surfactant. Time from birth to first InSurE

was 90 min (IQR 70–101) in the early surfactant group and

215 min (IQR 150–480) in the late surfactant group as

against 3 hours in our earlier published trial. Early

surfactant along with CPAP almost reduced the need for

mechanical ventilation (MV) within the first 7 days of

birth by nearly 50% (31.6% vs. 16.2%). Only 2infants in

the late group had BPD.

CPAP for any respiratory distress

The above two trials had given us critical inputs for

developing a protocol for CPAP usage. Our conviction to

use CPAP and early rescue surfactant improved, our

failure rates started to decline, our nasal injuries decreased

with increased experience and switch from Fisher and

paykel prongs to Hudson prongs. Considering the better

evidence for flow driver CPAP then, subsequent to these

trials, we evaluated if jet CPAP is better than bubble CPAP

in further reducing the need for mechanical ventilation in

preterm infants with respiratory distress.(5) In a open

labeled, two parallel arm, two center (PGIMER,

Chandigarh and Fernandez Hospital, Hyderabad)

randomized controlled trial (January 2011 to July 2012)

we enrolled 170 preterm infants (gestation <34

weeks)with respiratory distress within 6 h of birth into Jet

CPAP or bubble CPAP group. In the Jet-CPAP group the

device (NCPAP; Phoenix Medical Systems Private,

Chennai, India) was a stand-alone variable flow CPAP

device with a Benveniste valve that generates CPAP at the

level of the nostril with a short bi-nasal prongs as nasal

interface and in the bubble CPAP group a stand-alone

Bubble CPAP device (Bubble CPAP system with F & P

nasal interface—BC 163, Fisher and Paykel Healthcare,

Panmure, Auckland, New Zealand) with a flow rate just

enough to produce bubbling both during inspiration as

well as expiration was used to deliver CPAP. Early rescue

surfactant was administered for those infants with

FiO2>0.30 and the median age at surfactant

administration was 2 hours and the median age at starting

of CPAP was less than an hour after birth.Nearly 50% of the

enrolled infants were covered with complete antenatal

steroids course. Jet CPAP (34%) was as efficacious as

bubble CPAP (26%) in reducing the need for mechanical

ventilation in preterm infants with respiratory distress.

The mortality rate was 21% (36 of 170) and BPD occurred

in 23 infants (13.5%). In contrast to the first 2 trials, this

trial included all preterm infants with respiratory distress,

infants with gestation <28 weeks, enrolment was at 2

centers and antenatal steroid coverage was moderate.

In our endeavor to reduce failure rates of bubble CPAP for

primary respiratory distress in preterm infants (gestation

<33 weeks), we recently (2013 to 2015)evaluated the role

of higher starting CPAP pressures (7cms of H20) in

comparison to our standard CPAP pressures (5cms of H20)

in 271 infants. The results of this trial are under

consideration for publication elsewhere.

To simplify the use of CPAP in infants,in a clinical study

(April 2012 to December 2012)we evaluated if a fixed

flow is as good as regulated flow in delivering the set

pressures to the infants. (6) We compared the effects of a

fixed flow (5 L/min) and titrated flow (flow just enough to

ensure bubbling) at different set pressures on delivered

intra-prong pressure, gas exchange and clinical

parameters in 54 preterm infants on bubble CPAP for

respiratory distress. Preterm infants <35 weeks

gestational age on bubble CPAP and <96 h of age were

enrolled in this crossover study. They were subjected to

30-min periods of titrated flow and fixed flow. An

electronic manometer was used to measure the delivered

29


intra-prong pressures at the nasal interface. A total of 69

recordings were made in 54 infants. For each of the set

CPAP pressures (4, 5, and 6 cm H2O), the mean delivered

pressure with a fixed flow of 5 L/min was higher than that

delivered by the titrated flow. During the fixed flow epoch,

the delivered pressure was closer to and higher than the set

pressure resulting in higher PaO2 and lower PaCO2 as

compared to titrated flow epoch. In the titrated flow

period, the delivered pressure was consistently lower than

the set pressure. To our surprise, as against our routine

protocol of titrated flow, fixed flows performed better in

this trial. We have now adopted a fixed gas flow of 4 to 5

liters for all infants on bubble CPAP after this trial. As after

the study, of the 3 parameters required to be adjusted for

aninfant on bubble CPAP, one (i.e. the flow) has become a

fixed parameter and the other two, i.e. FiO2 and CPAP can

be adjusted from the oxygenation (SpO ), distress scoring 2

and inflation on chest x ray.

CPAP for meconium aspiration syndrome

As the use of CPAP had improved outcomes in preterm

infants, our confidence and determination to use CPAP in

term infants had increased. In a first of its experience we

evaluated the role of CPAP in term infants with meconium

aspiration syndrome (MAS).(7)By distending the airway

both during inspiration and expiration, CPAP is likely to

prevent air trapping, prevent secondary surfactant

deficiency by preventing alveolar collapse and thereby

improve the respiratory outcomes of infants with

meconium aspiration syndrome. From January 2012 to

May 2013, 97 infants were admitted with diagnosis of

MAS, out of which 66 infants were enrolled in the study.

Bubble or ventilator nasal CPAP was started if the SpO2 in

room air was <90%. Fifty (76%) out of 66 could be

managed only with CPAP. On logistic regression analysis,

only out-born status was independently associated with

CPAP failure (OR = 25, 95% CI: 1.5–300, P < 0.01) and

there was a trend towards CPAP failure in infants

depressed at birth (OR = 10, 95% CI: 0.9–122). Based on

this experience we are recruiting patients in a RCT to

evaluate if starting early CPAP in comparison to hood

oxygen reduces the need for mechanical ventilation

among infants with MAS with SpO2 <90% on room air at

admission.

Understanding the extensive use of CPAP in our level III

unit, we required measuring its potential in a level II SNCU

with limited staff, infrastructure and experience. We

utilized an opportunity where in our subsidiary low risk

obstetric unit with level II SNCU facilities, we introduced

CPAP and audited the respiratory and non-respiratory

outcomes before and after its introduction in the unit.(8)

Five hundred and fifty infants were admitted to the level II

SNCU, with 252 infants admitted 1 year before the

introduction of CPAP services and the rest 1 year after.

Introduction of CPAP reduced the overall up-transfers

(33% reduction) and more so in the VLBW infants (50%

reduction). Introduction of CPAP services reduced

transfers not only due to respiratory distress but also for all

illnesses as the medical staff became more confident in

managing the sick newborns in the level II SNCU. This

evidence supports the introduction of CPAP services in all

the well functioning and government run SNCUs across

the country.

Conclusions

Over the years we realized that CPAP as a respiratory

therapy for preterm infants is a boon and its application

improves with increased experience, conviction and

understanding the limitations. Although most infants in

our unit are on bubble CPAP for respiratory support, we

still have few infants requiring mechanical ventilation and

nasal IMV. We are still in search of an ideal interface,

which are more baby and parent friendly and equally

efficacious. There is a lot of promise and enthusiasm to use

heated humidified high flow nasal cannula(HHHFNC) as a

replacement for bubble CPAP but it still needs to be

studied. . We are presently recruiting infants in an RCT that

compares HHHFNC with bubble CPAP as a primary

respiratory support in preterm infants. From our

experience we conclude that

1. CPAP is the best respiratory therapy for preterm and

term infants with respiratory distress

2. Early CPAP with early rescue surfactant is the ideal

combination for improving the outcome of preterm

infants with RDS

3. In preterm infants with any respiratory distress,

bubble CPAP is as good as jet CPAP

4. For infants on bubble CPAP, a fixed flow of 5

liters/min irrespective of the set pressure is better than

titrated flow

5. Further evidence is required for routine and early

CPAP in term infants with MAS

6. Level II SNCUs should implement CPAP services to

improve overall outcomes of preterm infants and to

reduce up-transfers

30


References

1. Ho JJ, Subramaniam P, Davis PG. Continuous distending

pressure for respiratory distress in preterm infants.

Cochrane Database Syst Rev. 2015;7:CD002271.

2. Buckmaster AG, Arnolda G, Wright IMR, Foster JP,

Henderson-Smart DJ. Continuous positive airway pressure

therapy for infants with respiratory distress in non tertiary

care centers: a randomized, controlled trial. Pediatrics. 2007

Sep;120(3):509–18.

3. Koti J, Murki S, Gaddam P, Reddy A, Reddy MDR. Bubble

CPAP for respiratory distress syndrome in preterm infants.

Indian Pediatr. 2010 Feb;47(2):139–43.

4. Kandraju H, Murki S, Subramanian S, Gaddam P, Deorari A,

Kumar P. Early routine versus late selective surfactant in

preterm neonates with respiratory distress syndrome on

nasal continuous positive airway pressure: a randomized

controlled trial. Neonatology. 2013;103(2):148–54.

5. Bhatti A, Khan J, Murki S, Sundaram V, Saini SS, Kumar P.

Nasal Jet-CPAP (variable flow) versus Bubble-CPAP in

preterm infants with respiratory distress: an open label,

randomized controlled trial. J Perinatol Off J CalifPerinat

Assoc. 2015 Nov;35(11):935–40.

6. Murki S, Das RK, Sharma D, Kumar P. A Fixed Flow is More

Effective than Titrated Flow during Bubble Nasal CPAP for

Respiratory Distress in Preterm Neonates. Front Pediatr.

2015;3:81.

7. Bhagwat P, Murki S, Mehta A, Oleti T, Gannavaram D.

Continuous positive airway pressure in meconium

aspiration syndrome: An observational study. J

ClinNeonatol 2015;4:96-100.

8. Kiran S, Murki S, Pratap OT, Kandraju H, Reddy A. Nasal

continuous positive airway pressure therapy in a non-

tertiary neonatal unit: reduced need for up-transfers. Indian

J Pediatr. 2015 Feb;82(2):126–30.

31


Abstract

Among the various modalities of non-invasive support, nasal intermittent positive pressure ventilation (NIPPV) is increasingly being used in the management of the preterm neonate. Research on this modality of respiratory support continues to occur in order to assess the ideal patient population, the nasal interface, type of ventilator, respiratory support settings, the timing of initiation and duration of support, as well as weaning modalities. In this personal perspective, I attempt to provide evidence-based answers to frequently asked questions (FAQs) on the use of NIPPV in neonates.

Introduction

Nasal intermittent positive pressure ventilation (NIPPV) as a means of providing respiratory support to the neonate in the neonatal intensive care unit (NICU). NIPPV is a form of non-invasive ventilatory assistance combining

1-4nasal continuous positive airway pressure and IPPV. NIPPV may be synchronized (SNIPPV) or non-synchronized. In this personal perspective, evidence-based answers will be provided to frequently asked questions (FAQs) on the use of NIPPV in neonates.

Answers to FAQs

Question 1: Why is it necessary to differentiate between

the primary and secondary modes of NIPPV?

Answer 1: The primary mode of NIPPV refers to the use of

respiratory support soon after birth, up to d” 2 hours of

postnatal life. This may or may not include the use of

surfactant during this period. It is highly likely that the

condition of the premature lung in the first couple of hours

of life is more tenuous given the increased probability of

respiratory distress syndrome (RDS) and retention of lung

fluid, among other factors, as the infant makes the

transition to extra-uterine life. In such a scenario, it would

be expected that the settings required for respiratory

support (pressures, supplemental oxygen) would be higher

vis-à-vis those required at a later postnatal stage. The cut-

off value of 2 hours is based on the strong evidence that 5early administration of surfactant is preferred.

The secondary mode refers to its use following a period of

endotracheal tube (ETT) ventilation, usually for RDS,

lasting usually for day to weeks.

Question 2: Why is the preferred mode of nasal interface

to provide NIPPV?

Answer 2: While a variety of nasal prongs [short and long

(nasopharyngeal) uni- and bi- nasal] as well as nasal masks

have been used to provide NIPPV, no head-to-head studies

have been conducted to prove the ideal nasal interface.

Extrapolating data from NCPAP use, the short bi-nasal

prongs are recommended given the ease of use, and

decreased susceptibility to blockage secondary to 6, 7secretions.

Question 3: Which ventilators can provide NIPPV and

SNIPPV?

Answer 3: Any ventilator capable of providing NCPAP

and IPPV modes of ventilation in neonates can work in the

NIPPV mode. It is important to remember that in the

NIPPV in the Neonate: Answers to FAQS -

A Personal Perspective

Vineet Bhandari

Corresponding author:Vineet Bhandari, MD, DMDrexel University College of MedicineSt. Christopher’s Hospital for Children160 Erie Avenue, Philadelphia, PA 19134Phone: 215-427-5202Fax: 215-427-8192E-mail: [email protected]


32


majority of instances, the issues of nuisance alarms and

leak compensation can be overcome by modifications of

the software in the ventilator and appropriate nursing 3interventional strategies.

SNIPPV can be provided by the Infant Star with Star

Sync® (used a Graseby capsule for synchronization; this 8, 9ventilator has been discontinued in the USA), the

Sechrist IV-200 SAVI ventilator (Sechrist Industries, 10Anaheim, CA) , a nasal-flow synchronized ventilator

11(Giulia, Ginevri, Rome, Italy) , and using neurally

adjusted ventilatory assist (NAVA) in the Servo-i 12ventilator (Maquet Medical Systems, Wayne, NJ).

Question 4: Is bi-nasal positive airway pressure or Bi-PAP

same as NIPPV?

Answer 4: No. The Bi-PAP (if synchronized, it is known

as Si-PAP) device generates peak inspiratory pressures

(PIPs) that are typically 9-11 cmH O and uses much longer 2

3inspiratory times (Ti; up to 1 second). These settings are 2markedly different from those that I have advocated.

Question 5: Should infants be sedated while on NIPPV?

Answer 5: Never. It is critical that the inherent respiratory

drive of neonates not be compromised, as it is important for

the success of NIPPV. Caffeine should always be given 2, 3prior to extubation to NIPPV.

Question 6: Is SNIPPV better than NIPPV?

Answer 6: Most studies on the mechanism of this non-

invasive ventilation technique have shown a better

response of SNIPPV versus NIPPV in terms of improved

short-term effects such as improved stability of the chest

wall, improved pulmonary mechanics, thoraco-abdominal 13 motion synchrony and decreased flow resistance ,

14increased tidal and minute volumes , decreased work of 10, 15, 16breathing and reduced chest wall distortion as well as

17less desaturations/bradycardias/central apneas in infants

on SNIPPV. However, no definitive clinical study has

been reported showing the superiority of SNIPPV over

NIPPV in terms of longer-term clinical outcomes. In 1

retrospective study, use of NIPPV versus SNIPPV was not

associated with any difference in the clinical outcomes of

bronchopulmonary dysplasia (BPD)/death or other 18common neonatal morbidities.

Question 7: Can nasal cannula prongs be used to provide

NIPPV?

Answer 7: Yes. In our experience with one particular type

of nasal cannula prongs (Neotech RAM cannula®,

Valencia, CA), we noted that it was well tolerated in the 19neonatal population with the use of our guidelines.

Importantly, because of the design of the cannula, it cannot

be snugly fitted into the nares; hence, it is difficult to

provide NIPPV with higher pressures. Thus, we and

others have found it more useful in neonates with mild to

moderate lung disease and possibly apnea of prematurity 19, 20with normal lungs.

Question 8: Is growth of infants worse on NIPPV,

compared to those on ETT ventilation?

Answer 8: No. In a retrospective study, with infants

receiving equivalent nutritional support, there was no

difference in weight gain in infants on SNIPPV versus ETT 21ventilation.

Question 9: What is the ideal time to extubate infants to

NIPPV? Does repeated re-intubation increase the risk of

BPD? Which neonates fail NIPPV? What is the

subsequent management of such infants once they get re-

intubated?

Answer 9: The ideal time to extubate premature neonates

to NIPPV is the first 24 hours of postnatal life.

Importantly, delaying extubation beyond the first 3 days

was associated with an increased risk of BPD and 22BPD/death. Reintubation did not impact these

22outcomes. Furthermore, neonates who failed NIPPV

within 24 hours did not have any association with

likelihood of developing BPD or severity of BPD, after 23adjusting for confounding variables. Other investigators

have also reported that attempts at re-extubation should be 24made even if success is not guaranteed. Male sex and

lower weight infants were more likely to fail NIPPV and

get re-intubated, while higher gestational age at

extubation and female sex were both associated with 23increased time to failure. Three categories of infants

3have been recognized that fail NIPPV. Their clinical

presentation and the subsequent management have been 3described.

Question 10: What is the present status and future use of

NIPPV in preterm infants?

Answer 10: Currently, there is strong data to support the 3, 4use of (S)NIPPV in the secondary mode. In terms of

primary mode of (S)NIPPV, while it is safe and effective,

additional appropriately-designed studies with adequate

power are required to assess the ability to impact on

33


4BPD/death. I envisage that early use of NIPPV will be

increasingly accepted at NICUs around the globe. Most

studies that have reported benefit have used similar 9, 11, 25 26, 27ventilator settings in the SNIPPV or NIPPV

modes. It is important to realize that the efficacy of this

technique can be significantly affected if lower ventilator 28settings are used. There is marked variation in the

ventilator settings being utilized for delivering NIPPV in

the NICUs worldwide, which possibly contributes to the

variable results reported vis-à-vis the efficacy of this 4, 7, 29, 30, 31technique. It is important that published evidence-

based guidelines of NIPPV be used for maximum potential 1, 2for benefit. The future trend appears to be combining

early NIPPV, with minimally-invasive modes of 32surfactant administration.

Conclusions

NIPPV has been shown to be safe and effective as a mode

of extubation in premature neonates after a period of ETT

ventilation (i.e. secondary mode). More studies are

required to establish the efficacy of using early NIPPV,

with or without surfactant administration (i.e. primary

mode). I hope the answers to FAQs on NIPPV will provide

some guidance on using this technique effectively in

preterm neonates.

References

1. Bhandari V. Non-invasive ventilation of the sick neonate:

evidence-based recommendations. Journal of Neonatology.

2006;20:214-221.

2. Bhandari V. Nasal intermittent positive pressure ventilation

in the newborn: review of literature and evidence-based

guidelines. J Perinatol. 2010;30:505-512.

3. Bhandari V. Noninvasive respiratory support in the preterm

infant. Clin Perinatol. 2012;39:497-511.

4. Bhandari V. The potential of non-invasive ventilation to

decrease BPD. Semin Perinatol. 2013;37:108-114.

5. Bahadue FL, Soll R. Early versus delayed selective

surfactant treatment for neonatal respiratory distress

s y n d r o m e . C o c h r a n e D a t a b a s e S y s t R e v .

2012;11:CD001456.

6. Bhandari V, Rogerson S, Barfield C, Yu VY, Rowe J. Nasal

versus nasopharyngeal continuous positive airway pressure

use in preterm neonates. Pediatr Res 1996;39:196A

(Abstract No. 1163).

7. Davis PG, Morley CJ, Owen LS. Non-invasive respiratory

support of preterm neonates with respiratory distress:

continuous positive airway pressure and nasal intermittent

positive pressure ventilation. Semin Fetal Neonatal Med.

2009;14:14-20.

8. Khalaf MN, Brodsky N, Hurley J, Bhandari V. A prospective

randomized, controlled trial comparing synchronized nasal

intermittent positive pressure ventilation versus nasal

continuous positive airway pressure as modes of extubation.

Pediatrics. 2001;108:13-17.

9. Barrington KJ, Bull D, Finer NN. Randomized trial of nasal

synchronized intermittent mandatory ventilation compared

with continuous positive airway pressure after extubation of

very low birth weight infants. Pediatrics. 2001;107:638-

641.

10. Ali N, Claure N, Alegria X, D’Ugard C, Organero R,

Bancalari E. Effects of non-invasive pressure support

ventilation (NI-PSV) on ventilation and respiratory effort in

very low birth weight infants. Pediatr Pulmonol.

2007;42:704-710.

11. Moretti C, Giannini L, Fassi C, Gizzi C, Papoff P, Colarizi P.

Nasal flow-synchronized intermittent positive pressure

ventilation to facilitate weaning in very low-birthweight

infants: unmasked randomized controlled trial. Pediatr Int.

2008;50:85-91.

12. Beck J, Reilly M, Grasselli G, et al. Patient-ventilator

interaction during neurally adjusted ventilatory assist in low

birth weight infants. Pediatr Res. 2009;65:663-668.

13. Kiciman NM, Andreasson B, Bernstein G, et al.

Thoracoabdominal motion in newborns during ventilation

delivered by endotracheal tube or nasal prongs. Pediatr

Pulmonol. 1998;25:175-181.

14. Moretti C, Gizzi C, Papoff P, et al. Comparing the effects of

nasal synchronized intermittent positive pressure

ventilation (nSIPPV) and nasal continuous positive airway

pressure (nCPAP) after extubation in very low birth weight

infants. Early Hum Dev. 1999;56:167-177.

15. Aghai ZH, Saslow JG, Nakhla T, et al. Synchronized nasal

intermittent positive pressure ventilation (SNIPPV)

decreases work of breathing (WOB) in premature infants

with respiratory distress syndrome (RDS) compared to

nasal continuous positive airway pressure (NCPAP).

Pediatr Pulmonol. 2006;41:875-881.

16. Chang HY, Claure N, D’Ugard C, Torres J, Nwajei P,

Bancalari E. Effects of synchronization during nasal

ventilation in clinically stable preterm infants. Pediatr Res.

2011;69:84-89.

17. Gizzi C, Montecchia F, Panetta V, et al. Is synchronised

NIPPV more effective than NIPPV and NCPAP in treating

apnoea of prematurity (AOP)? A randomised cross-over

trial. Arch Dis Child Fetal Neonatal Ed. 2015;100:F17-23.

18. Dumpa V, Katz K, Northrup V, Bhandari V. SNIPPV vs

NIPPV: does synchronization matter? J Perinatol.

2011;Nov. 24:[E-pub ahead of print].

19. Nzegwu NI, Mack T, DellaVentura R, et al. Systematic use

of the RAM nasal cannula in the Yale-New Haven

Children’s Hospital Neonatal Intensive Care Unit: a quality

improvement project. J Matern Fetal Neonatal Med.

2015;28:718-721.

20. Moretti C, Marzetti G, Agostino R, et al. Prolonged

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intermittent positive pressure ventilation by nasal prongs in

intractable apnea of prematurity. Acta Paediatr Scand.

1981;70:211-216.

21. Kulkarni A, Ehrenkranz RA, Bhandari V. Effect of

introduction of synchronized nasal intermittent positive-

pressure ventilation in a neonatal intensive care unit on

bronchopulmonary dysplasia and growth in preterm infants.

Am J Perinatol. 2006;23:233-240.

22. Berger J, Mehta P, Bucholz E, Dziura J, Bhandari V. Impact

of early extubation and reintubation on the incidence of

bronchopulmonary dysplasia in neonates. Am J Perinatol.

2014;31:1063-1072.

23. Mehta P, Berger J, Bucholz E, Bhandari V. Factors affecting

nasal intermittent positive pressure ventilation failure and

impact on bronchopulmonary dysplasia in neonates. J

Perinatol. 2014;34:754-760.

24. Jensen EA, DeMauro SB, Kornhauser M, Aghai ZH,

Greenspan JS, Dysart KC. Effects of Multiple Ventilation

Courses and Duration of Mechanical Ventilation on

Respiratory Outcomes in Extremely Low-Birth-Weight

Infants. JAMA pediatrics. 2015;169:1011-1017.

25. Friedlich P, Lecart C, Posen R, Ramicone E, Chan L,

Ramanathan R. A randomized trial of nasopharyngeal-

synchronized intermittent mandatory ventilation versus

nasopharyngeal continuous positive airway pressure in very

low birth weight infants after extubation. J Perinatol.

1999;19:413-418.

26. Kugelman A, Feferkorn I, Riskin A, Chistyakov I, Kaufman

B, Bader D. Nasal intermittent mandatory ventilation versus

nasal continuous positive airway pressure for respiratory

distress syndrome: a randomized, controlled, prospective

study. J Pediatr. 2007;150:521-526

27. Bisceglia M, Belcastro A, Poerio V, et al. A comparison of

nasal intermittent versus continuous positive pressure

delivery for the treatment of moderate respiratory syndrome

in preterm infants. Minerva Pediatr. 2007;59:91-95.

28. Khorana M, Pa radeev i su t H , Sang t awes in V,

Kanjanapatanakul W, Chotigeat U, Ayutthaya JK. A

randomized trial of non-synchronized Nasopharyngeal

Intermittent Mandatory Ventilation (nsNIMV) vs. Nasal

Continuous Positive Airway Pressure (NCPAP) in the

prevention of extubation failure in pre-term < 1,500 grams. J

Med Assoc Thai. 2008;91 Suppl 3:S136-142.

29. de Medeiros SK, Carvalho WB, Soriano CF. Practices of use

of nasal intermittent positive pressure ventilation (NIPPV)

in neonatology in northeastern Brazil. J Pediatr (Rio J).

2012;88:48-53.

30. Kirpalani H, Millar D, Lemyre B, Yoder BA, Chiu A,

Roberts RS. A trial comparing noninvasive ventilation

strategies in preterm infants. N Engl J Med. 2013;369:611-

620.

31. Ramanathan R, Sekar KC, Rasmussen M, Bhatia J, Soll RF.

Nasal intermittent positive pressure ventilation after

surfactant treatment for respiratory distress syndrome in

preterm infants <30 weeks’ gestation: a randomized,

controlled trial. J Perinatol. 2012;32:336-343.

32. Oncel MY, Arayici S, Uras N, et al. Nasal continuous

positive airway pressure versus nasal intermittent positive-

pressure ventilation within the minimally invasive

surfactant therapy approach in preterm infants: a

randomised controlled trial. Arch Dis Child Fetal Neonatal

Ed. 2015.

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35


Among the various modalities of non-invasive support, nasal intermittent positive pressure ventilation (NIPPV) is increasingly being used in the management of the preterm neonate. Research on this modality of respiratory support continues to assess the ideal patient population, the nasal interface, type of ventilator, respiratory support settings, the timing of initiation and duration of support, as well as weaning modalities.

Why noninvasive ventilation ?

Nasal continuous positive airway pressure (NCPAP) alone or in combination with INSURE has found to reduce further the risks associated with invasive ventilation while demonstrating a trend toward a lower incidence of BPD. However, not all infants who are given early NCPAP can be successfully managed, and studies have revealed failure rates that range from 25% to 50% which has encouraged the use of nasal intermittent positive-pressure ventilation (NIPPV) to reduce these failure rates.The Continuous Positive Airway Pressure or Intubation at Birth (COIN) trial found the outcome of oxygen dependency at 28 days of age lower in the NCPAP group, although this was not

1seen at 36 weeks’ postmenstrual age. The more recent Surfactant, Positive Pressure and Pulse Oximetry Randomized Trial (SUPPORT) revealed no difference in the primary outcome of death or BPD between infants

2assigned to early NCPAP or early surfactant and MV.

Bhandari et al evaluated SNIPPV and surfactant therapy,

compared with continued ETT MV, and found a

significantly lower primary outcome of BPD/ death in the

3 4SNIPPV group. From a recent trial, Ramanathan et al also

reported a significant reduction in clinical BPD in the

NIPPV group. Results of these studiessuggest that NIPPV

seems to be feasible and effective and results in a lower

incidence of BPD when compared with MV.

The impact of NCPAP compared with SNIPPV on the

incidence of BPD was evaluated in a large retrospective

study in infants with a birthweight equaling 1250 g. In the

subgroup of those born at 500 to 750 g, SNIPPV was

associated with a significant lower incidence of BPD

(P<.01), as well as the composite outcome BPD/death (P < 5 6.01), when compared with NCPAP. Kugelman et al also

found a substantial decrease in the incidence of BPD in the

NIPPV group among the subgroup of infants born at<1500

g (5% vs 33%; P < .04) when compared with NCPAP.

NIPPV- aim is to mimic invasive ventilation, using short

inflation times (0.3–0.5 s), variable inflation rates of

10–60/ min, with PIP and PEEP similar to those used with

endotracheal ventilation.It can be used in a synchronized

(SNIPPV) or nonsynchronized manner to supplement the

infants’ own breathing efforts.

Types of triggers for synchronization

1. Most randomised studies evaluating SNIPPV used a

pneumatic capsule to detect abdominal movement.

However, the ventilators using these capsules are no

longer commercially available.

2. SiPAP device offers synchronisation using a similar

abdominal capsule, although this is not approved for

use within the United States.

3. Pneumotachograph (f low-tr igger) to detect

inspiratory flow. However, flow triggering during

non-invasive respiratory support in neonates is

affected by leaks at the mouth and nose.

4. Pressure trigger to attempt synchronisation

Non- Invasive Ventilation in Neonatal RDS

The Way to Go!

N. Karthik Nagesh, Mrinal Pillai


Prof. N Karthik Nagesh,

Chairman-HOD of Neonatology & MACC,

Manipal Advanced Children’s Centre(MACC),

Manipal Hospitals, Bangalore, India


[email protected]


36


5. Synchronised NIPPV using respiratory inductance plethysmography

6. NAVA: synchronises vent i la t ion us ing a diaphragmatic electromyogram.

7Kiciman et al found reduced thoracoabdominal motion asynchrony during SNIPPV when compared with NCPAP.

8Aghai et al revealed that SNIPPV decreases the work of breathing in preterm infants. The short bi-nasal prongs are recommended given the ease of use, and decreased susceptibility to blockage secondary to secretions. Any ventilator capable of providing NCPAP and IPPV modes of ventilation in neonates can work in the NIPPV mode.

Three indications for NIV:

1. Primary respiratory support

2. Post extubation support

3. Apnea of Prematurity

1. Primary respiratory support

a) Synchronised NIPPV: An RCT by Kugelman et al (n = 84) evaluated SNIPPV vs NCPAP, as a mode of primary respiratory support. They found significantly lower intubation rates in the

6SNIPPV group (25 vs. 49%, p < 0.04).

b) Nonsynchronised NIPPV: In one study by Sai Sunil et al (n = 76), ‘Failure of treatment’ within 48 h occurred in fewer of the nsNIPPV group

9(13.5 vs. 35.9%, p < 0.024). Two other studies found no difference in intubation rates, one at 4 h of age (n = 88), the other at 72 h of age (n =

10,11200).

A recent meta-analysis combined this ‘SNIPPV’ study with two nsNIPPV studies and demonstrated a relative risk reduction for intubation in the first 72 h in the NIPPV group compared to NCPAP (RR 0.60, 95% CI 0.43,

120.83).

2. Post extubation support

a. Synchronised NIPPV: Meta-analysis of three studies, which used a pneumatic capsule for synchronisation, showed a clinically important advantage of SNIPPV over NCPAP in preventing extubation failure, RR 0.21 (95% CI 0.10, 0.45) and number needed to treat of three

13(95% CI 2, 5).

A further RCT used an inspiratory flow sensor as a

means of synchronising NIPPV and also demonstrated lower re-intubation rates in the

14SNIPPV group (6 vs. 39%, p < 0.005).

b. Nonsynchronised NIPPV: Khorana et al reported no difference in re-intubation rates at 7 days; however, the groups had significant demographic

15differences.

Ramanathan et al reported a significant decrease in infants requiring mechanical ventilation at 7 days of age in the nsNIPPV group (17 vs. 42%, OR 3.6, CI 1.5, 8.7, p = 0.005). However, in this study the comparison group, by design, received longer dura t ion o f in i t i a l mechan ica l

16ventilation. It is therefore unclear if there is benefit of nsNIPPV overNCPAP, as a post-extubation therapy.

3. Apnea of Prematurity

• Ryan et al found no benefit of ns NIPPV in 20 infants <32 weeks’ gestation.

• Lin et al assessed 34 aminophylline-treated, premature infants and found a significantly greater reduction in apnoeic events in the nsNIPPV group.

• A Cochrane review including the studies by Lin and Ryan concluded that NIPPV may augment the effects of NCPAP in apnoea that is frequent or severe, but only short-term effects were studied, and more data are required before NIPPV could be recommended as a

17therapy for apnoea.

BiPAP- use of longer high NCPAP times (0.5–1.0 s), lower cycle rates (10–30/min) and d” 4 cm H 2 O difference between high and low NCPAP levels. BiPAP has not been shown to provide benefit over NCPAP as primary or post-extubation therapy.

SiPAP-NCPAP flow drivers, such as SiPAP (Care Fusion, Yorba Linda, Calif., USA), and its predecessor, the Infant Flow Driver advance (IFDa), can deliver both NIPPV and BiPAP.Flow drivers are limited by the maximum deliverable pressure (11 cm H 2 O for the IFDa, and 11–15 cm H 2 O for the SiPAP, depending on its operating mode), although chosen set pressures are often well below these maximums. SiPAP device as synchronised primary respiratory support in preterm infants, demonstrated no reduction in intubation rate at 72 h of age compared to NCPAP.

NAVA-Neurally adjusted ventilator assist offers the a t t r ac t ive poss ib i l i t y o f p rov id ing no t on ly

37


synchronisation timed with the patient’s inspiratory effort, but also providing pressure support proportional to the infant’s inspiratory effort. However, it has the disadvantage of being invasive and costly, and to date there

18are little data on clinical outcomes.

Conclusion

• It is clear that non-invasive respiratory support is preferable to prolonged mechanical ventilation when possible.

• Synchronised NIPPV confers an advantage over NCPAP as a mode of post-extubation respiratory support.

• There is some evidence to suggest that NIPPV (synchronised or non-synchronised) may be useful as a mode of primary respiratory support.

• BiPAP has not been shown to provide benefit over NCPAP as primary or post-extubation therapy.

• There is no clear benefit for the use of NIPPV or BiPAP in treating apnea of prematurity.

References

1. 1.Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB; COIN Trial Investigators. Nasal CPAP or intubation at birth for very preterm infants.N Engl J Med. 2008;358(7): 700 –707

2. 2.SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network; Finer NN, Carlo WA, Walsh MC, et al. Early CPAP versus surfactant in extremely preterm infants [published correction appears in N Engl J M e d . 2 0 1 0 ; 3 6 2 ( 2 3 ) : 2 2 3 5 ] . N E n g l J M e d . 2010;362(21):1970 –1979.

3. 3.Bhandari V, Gavino RG, Nedrelow, et al. A randomized controlled trial of synchronizednasal intermittent positive pressure ventilation in RDS. J Perinatol. 2007;27(11): 697–703.

4. Ramanathan R, Sekar K, Ramsmussen M, Bhatia J, Soll R. Nasal intermittent mandatory ventilation (NIPPV) versus synchronized intermittent mandatory ventilation (SIMV) after surfactant treatment for respiratory distress syndrome (RDS) in preterm infants < 30 weeks gestation: multicenter, r a n d o m i z e d , c l i n i c a l t r i a l [ a b s t r a c t ] . E PA S . 2009;3213:3216.

5. 5.Bhandari V, Finer NN, Ehrenkranz RA, et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Synchronized nasal intermittent positive-pressure vent i la t ion and neonatal outcomes. Pediatr ics . 2009;124(2):517–526.

6. Kugelman A, Feferkorn I, Riskin A, Chistyakov I, Kaufman B, Bader D. Nasal intermittent mandatory ventilation versus

nasal continuous positive airway pressure for respiratory distress syndrome: a randomized, controlled, prospective study. J Pediatr. 2007;150(5):521–526.

7. 7.Kiciman NM, Andreasson B, Bernstein G, et al. Thoracoabdominal motion in newborns during ventilation delivered by endotracheal tube or nasal prongs. PediatrPulmonol. 1998;25(3):175–181

8. 8.Aghai ZH, Saslow JG, Nakhala T, et al. Synchronized nasal intermittent positive pressure ventilation (SNIPPV) decreases work of breathing (WOB) in premature infants with respiratory distress syndrome (RDS) compared to nasal con t inuous pos i t i ve a i rwaypre s su re (NCPAP) . PediatrPulmonol. 2006; 41(9):875– 881

9. Sai Sunil Kishore M, Dutta S, Kumar P: Early nasal intermittent positive pressure ventilationversus continuous positive airway pressure for respiratory distress syndrome. ActaPaediatr 2009; 98: 1412–1415.

10. 10.Meneses J, et al: Noninvasive ventilation for respiratory distress syndrome: a randomized controlled trial. Pediatrics 2011; 127: 300–307.

11. 11.Bisceglia M, et al: A comparison of nasal intermittent versus continuous positive pressure delivery for the treatment of moderate respiratory syndrome in preterm neonates. Minerva Pediatr 2007; 59: 91–95.

12. Meneses J, Bhandari V, Alves JG: Nasal intermittent positive-pressure ventilation vs nasal continuous positive airway pressure for preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch PediatrAdolesc Med 2012; 166: 372– 376.

13. Davis PG, Lemyre B, de Paoli AG: Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation. Cochrane Database Syst Rev 2001:CD003212.

14. Moretti C, et al: Nasal flow-synchronized intermittent positive pressure ventilation to facilitate weaning in very low-birth-weight infants: unmasked randomized controlled trial. Pediatr Int 2008; 50: 85–91.

15. Khorana M, et al: A randomized trial of nonsynchronized nasopharyngeal intermittentmandatory ventilation (nsNIMV) vs. nasal continuous positive airway pressure (NCPAP) in the prevention of extubation failure in pre-term <1,500 grams. J Med Assoc Thai 2008; 91(suppl 3):S136–S142.

16. Ramanathan R, et al: Nasal intermittent positive pressure ventilation after surfactant treatment for respiratory distress syndrome in preterm infants <30 weeks’ gestation: a randomized, controlled trial. J Perinatol 2012; 32: 336–343.

17. Lemyre B, Davis PG, De Paoli AG: Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for apnea of prematurity. Cochrane Database Syst Rev 2000:CD002272.

18. Beck J, et al: Patient-ventilator interaction during neurally adjusted ventilatory assist in low birth weight infants. Pediatr Res 2009; 65: 663–668.

38


Introduction

Bronchopulmonary dysplasia (BPD) is a chronic

respiratory condition affecting mainly extreme preterm

infants. It is amultifactorial disease and is associated with

long term complications, including neurodevelopmental

delay, chronic respiratory conditions such as abnormal

pu lmonary func t ions , as thma and pu lmonary

hypertension. Theincidence in< 28 weeks of gestational

age infants is between 35% to 50%, and has remained 1,2unchanged or increased in recent years .

The mechanical ventilation and surfactant therapy has

improved survival of RDS over last many years, however

mechanical ventilation does cause lung injury. Even short-

term invasive ventilation in animal models of respiratory

distress has been associated with lung inflammation and

injury, reduced efficacy of endogenous surfactant, and 3arrest of alveolar growth and development . Ventilator

induced lung injury (VILI) is characterized by excessive

tidal volume delivery (volutrauma), shear injury related to

repetitive cycling of distal airways at suboptimal lung

volumes (atelectrauma), and the consequent release of

biochemical substances causing pulmonaryinflammation

(biotrauma). VILI has been implicated as a major risk

factor predisposing preterm newborns to chronic lung 4,5disease or BPD . More so, procedure of endotracheal

intubation and ventilation through the endotracheal tube

also causes injury to the airways and lungs and is termed 6asEndotrauma .Although, current ventilation and

management strategies have been aimed to reduce post-

natal lung injury,effective therapy for prevention and

treatment of BPD is lacking. In an effort to avoid

mechanical ventilation and endotracheal intubation, a

major risk factor for BPD, neonatologist have attempted

using non invasive ventilation for treatment of respiratory

disease in premature infants.

Non invasive ventilation

Noninvasive ventilation is method of delivery of assisted ventilation without endotracheal intubation and is increasingly being used in preterm neonates to improve lung compliance and stabilize functional residual capacity (FRC). It include nasal continuous positive airway pressure (NCPAP), nasal intermittent positive airway pressure (NIPPV/SNIPPV), high flow nasal cannula therapy (HHHFNC) and nasal high frequency ventilation (NHFV).

Nasal continuous positive airway pressure (NCPAP)

NCPAP is an alternative to invasive ventilation that does not require an endotracheal intubation and permits spontaneous breathing during continuous pressure being applied to lungs externally through nose. CPAP improves gas exchange, increases FRC, stabilizes the chest wall, enhances surfactant production, reduces work of breathing, and reduces the need for intubation. Now a day, itis an established method of providing initial respiratory support to preterm infants.

NCPAP alone and BPD

Early application of NCPAP conserves infant’s own

surfactant and could reduce lung trauma and thereby BPD.

In 1987, Avery et al reported that the application of early 7NCPAP was associated with reduced rates of BPD . COIN

trial (Continuous Positive Airway Pressure or Intubation

Non-Invasive Ventilation and its Impact on

Bronchopulmonary Dysplasia

Naveen Bajaj


Naveen BajajConsultant Neonatologist, Deep Hospital,

Ludhiana, Punjab E mail: [email protected]


39


at Birth) included 610 infants of 25-28 week’s gestation

and compared early NCPAP with intubation and

ventilation at birth. NCPAP group had more incidences of

pneumothorax but had fewer days of ventilation and fewer

infants received oxygen at 28 days. However, there was no 8significant reduction in rate of BPD or death . SUPPORT

(Surfactant, Positive Pressure, and Oxygenation

Randomized Trial) enrolled 1316 infants of 24 to <28

week’s gestation and didn’t find any difference in BPD or

death in NCPAP initiated in the delivery room vs

intubation and surfactant (within 1 hour after birth) 9groups . A recent meta analysis, on use of CPAP for RDS

10also found no difference in rates of BPD .Logically,early

use of NCPAPshould reduce lung injury and thereby

incidence of BPD, however, recent evidence doesn’t

support this logic.Not providing surfactant therapy to the

surfactant deficient preterm infants who were on NCPAP

might be the reason for non-reduction of BPD in the above

mentioned studies.

NCPAP and sustained lung inflation

With the aim of improving FRC, the “sustained lung

inflation” (SLI)maneuverat birth has been recently triedin

preterm infants with respiratory distress. In a prospective

study, SL Imaneuver at birth followed by NCPAP has been

found to reduce the need for intubation and surfactant and 11the BPD rate when compared with NCPAP alone .

However, a recent RCT conducted on 25 to 28

weeksgestational age infants,concluded that SLI (25 cm

H O for 15 seconds) followed by NCPAP in the delivery 2

room decreased the need for MV in the first 72 hours of

lifecompared with NCPAP alone but did not decrease the 12need for respiratory support and the incidence of BPD .

NCPAP with INSURE strategy and BPD

The Scandinavian approach of primary NCPAP in

combination with early rescue surfactant followed by

rapid extubation to NCPAP, is called the INSURE (

IntubationSurfactant and Extubation) strategy. First RCT

of use of surfactant during NCPAP showed that a single

dose of surfactant reduced the need for MV by half, from 1385% without surfactant to 43% . Later RCT confirmed

that the effect is even more pronounced if surfactant is 14given as early rescue treatment . NCPAP and INSURE

strategy hence reduce need for mechanical ventilation and

have the potential to reduce VILI.

Most observational studies have also shown that INSURE

may diminish the development of BPD. In a Cochrane

meta-analysisof six RCTs, Early surfactant administration

with brief mechanical ventilation (<1 hour) followed by

extubationto NCPAP compared with later selective

surfactant administration, continued mechanical

ventilation, and extubation from low respiratory support, 15was associated with decreased incidence ofBPD . More

so, lower treatment threshold strategy (FiO < 0.45) is 2

better in reducing the incidences of air leak syndromes and 1 5BPD . In ano ther mul t i cen t r i c RCT on 27-

31weeks’gestation infants, NCPAP at birth combined with

very early surfactant within the first hour of life reduced

the need for mechanical ventilation, the incidence of air 16leaks and BPD compared to NCPAP alone . CURPAP

RCTincluded 208 preterm infants of 25-28 weeks

gestational age who were not intubated at birth, and

compared prophylactic surfactant followed by NCPAP or

NCPAP and early selective surfactant. Prophylactic

surfactant followed by NCPAP was not found to be

superior to NCPAP and early selective surfactant in

decreasing the need for mechanical ventilation in the first 175 days of life and BPD .VON-DRM (Vermont Oxford

Network centres - Delivery Room Management), a

multicenter randomized trial was conducted on 26-29

week preterm infants and compared prophylactic

surfactant followed by a period of mechanical ventilation

(prophylactic surfactant [PS]); prophylactic surfactant

with rapid extubation to bubble NCPAP (intubate-

surfactant-extubate [ISX]) or initial management with

bubble NCPAP and selective surfactant treatment

(NCPAP). There were no significant differences in 18mortality and other complications including BPD .A

recent meta-analysis also supportthat early stabilization

on NCPAP and selective surfactant administration reduce 19BPD or death . The main effect of surfactant probably is

by improving the capacity of preterm infant to breathe on

NCPAP and hence reducing the need for mechanical

ventilation and thereby lessening barotraumas and BPD.

The physiologic effects of caffeine may increase the

success of early initial CPAP or facilitate weaning from the

ventilator and result in a reduction of mechanical

ventilation thereby protecting against associated lung

injury. These potential benefits of caffeine are supported 20by findings of CAP trial . The caffeine treatment in a meta-

analysis has also been shown to reduce the development 21ofBPD . In fact, using caffeine early rather than late

reduces the mechanical ventilation days and BPD 22signiûcantly .

40


To avoid the trauma of inserting endotracheal tube for

delivery of surfactant, alternative method of inserting a

thin catheter into the trachea “Less invasive surfactant

administration (LISA)” has been successfully tried.

Though, LISA did not increase survival without BPD but

was associated with increased survival without major 23complications like pneumothorax and severe IVH and

hold a promising future.

To summarize, there is a strong evidence to suggest that

initial stabilization on NCPAP followed by early selective

surfact antreplacement therapy by INSURE and early

caffeine therapy reduces the incidence of BPD.

Nasal intermittent positive pressure ventilation

(NIPPV) and synchronized NIPPV (SNIPPV)

NIPPV, anon invasive mode of ventilation has come into

use as an attempt to avoid intubation but to retain the

clinical benefits of positivepressure ventilation. The

results from a short-term study (6 hours) on animal

demonstrated that noninvasive IMV may be less injurious 24to the lung than invasive IMV . As approximately 25-38%

of infants treated with NCPAP along with surfactant fail

this strategy, alternative modes of non invasive

ventilation like NIPPV/SNIPPV has been tried. It is useful

intermediate strategy that offers superimposed breaths on

NCPAP for neonates weaning from mechanical ventilation

or who cannot be supported by CPAP. The primary mode of

NIPPV refers to its use soon after birth with or without a

short period (<2 hours) of intubation for surfactant

delivery, followed by extubation. The secondary mode

refers to its use following a longer period (>2 h to days to 25weeks) of intubation . Although a recent retrospective

study suggests no differential impact on clinical outcomes

between NIPPV and SNIPPV, several observations favour

SNIPPV.

NIPPV/SNIPV and BPD

Meta analysis of 3 studies couldn’t find any difference in

the incidence of BPD between NIPPV and NCPAP 26groups . Another large RCT in ELBW infants also

documented no difference in BPD between NIPPV vs. 27NCPAP . However, amulticentric RCT on preterm

infants <30 weeks’ gestation requiring intubation and

surfactant for RDS, found that early extubation to NIPPV

versus NCPAP reduced the need for mechanical

ventilation via endotracheal tube (MVET) in the first

week, duration of MVET, and clinical as well as 28physiological BPD .

A large retrospective analysis comparing SNIPPV and

CPAP found decreased BPD in 500-750 gm group infants.

There was no difference in BPD in higher birth weight 29groups . A RCT comparing preterm infants (600-1250

gm) on primary mode of SNIPPV (extubation to SNIPPV

after surfactant) with infants who were continued on

conventional ventilation after surfactant, found 30significantly lower BPD in SNIPPV group .

Few studies do favour the use of NIPPV/SNIPPV but the

evidence available from RCT is too small to suggest that its

use reduces the incidence of BPD.

Heated humidified high flow nasal cannula

(HHHFNC) and BPD

HHHFNC is a form of non invasive respiratory support in

whichrespiratorygases are delivered through a nasal

cannula at rate > 2 lpm (2-8 lpm) accompanied by optimal

heating (37°C) and humidification (100%).Arecent

multicenteric RCT compared HHFNC and NCPAP

involving preterm infants of <28 weeks gestational age

undergoing planned non-invasive respiratory support

either as initial respiratory support or after mechanical

ventilation. No significant difference in need for

intubation withinthe initial 72 hours of support, duration

of oxygen supplementation, diagnosis of BPD, or

discharge from the hospital on oxygen has been found

between two groups. In postextubation period also

HHFNC and NCPAP has been found to be equally

effective. Further research on use of HHFNC and its effect 31on BPD is warranted .

Nasal high frequency ventilation (NHFV) and BPD

Over the last decade, nasal high-frequency ventilation

(NHFV) has been tried in neonates as a form of NIV.

Unlike nasal IMV, nasal HFV uses lower pressure and

smaller volume at higher frequency, and may be more

lung-protective. In a case study, Hoehn et al described the

first successful application of nasal HFV in 760 gm (27

weeks) infant with severe CO retention, acidosis, and 2

32respiratory distress .In aanimal study, NHFV resulted in

smaller and more uniformly inflated terminal respiratory

units and distal air spaces, longer alveolar secondary

septae, thandidinvasiveconventionalventi lat ion,

implying that short-term NHFV may optimize lung

recruitment and promote normal alveolarization in 33preterm lungs better than invasive ventilation strategy .

Unfortunately, very few data on NHFV is available to

41


suggest its role in management of acute respiratory disease

like RDS and its implication on chronic respiratory disease

like BPD.

Summary

BPD remains a significant cause of short and long term

morbidity in extreme preterm infants. Realization of the

fact that mechanical ventilation is one of the main culprits

in development of BPD, has led researches to study non

invasivemodalities of ventilation. Evidence available at

present suggest that reduction in incidence ofBPD can be

achieved with early use of NCPAP combined with

INSURE strategy and early caffeine therapy,and seems to

be the ideal approach for respiratory management of

preterm infants.NIPPV/SNIPPV has the potential to

reduce lung injury, however further research is warranted

to prove its usefulness in reducing BPD.

Summary of studies (RCT/Review): Non invasive ventilation and its impact on BPD

Study Design Impact on BPD

Nasal CPAP alone

COIN trial (2008) Early NCPAP vs. intubation and ventilation at birth No difference

SUPPORT (2010) NCPAP initiated in the delivery room vs. intubation

and surfactant No difference

Cochrane Review (2015) CPAP for RDS in preterm No difference

NCPAP and SLI

Lista et al (2015) SLI followed by NCPAP at birth vs. NCPAP alone No difference

NCPAP and INSURE strategy

Cochrane Review (2007) Early surfactant with brief mechanical ventilation Reduction in BPDFavors early

(<1 hour) followed by extubation to NCPAP vs. surfactant and extubation to

later selective surfactant, continued mechanical NCPAP

ventilation, and extubation from low respiratory

support

Rojas et al CNRN (2009) NCPAP at birth and very early surfactant (<1 hour) Reduction in BPDFavors NCPAP

vs NCPAP alone + early surfactant

CURAP (2010) Prophylactic surfactant followed by NCPAP vs.

NCPAP and early selective surfactant No difference

VON-DRM (2011) Prophylactic surfactant vs. prophylactic surfactant

with rapid extubation to NCPAP vs. NCPAP and

selective surfactant treatment No difference

Cochrane Review (2012) Prophylactic vs. selective use of surfactant and Reduction in BPD Favors NCPAP

NCPAP + selective surfactant

NIPPV/SNIPPV

Meneses et al,/Review (2012) NIPPV vsNCPAP No difference

Kirpalani et al (2012) NIPPV vs NCPAP No difference

Ramanathan et al (2012) NIPPV vs NCPAP Reduction in BPDFavors NIPPV

Bhandari et al (2007) Mechanical ventilation vs Primary SNIPPV Reduction in BPD Favors

Primary SNIPPV

HHFNC

Bradley et al. (2013) HHFNC vs.NCPAP No difference

42


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2. Shah PS, Sankaran K, Aziz K et al. Outcomes of preterm

infants <29 weeks gestation over 10-year period in Canada:

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3. Jobe AH, Kramer BW, Moss TJ et al. Decreased indicators of

lung injury with continuous positive expiratory pressure in

preterm lambs. Pediatr Res 2002;52(3):387-392.

4. Avery ME, Tooley WH, Keller JB, Hurd SS, Bryan MH,

Cotton RB, et al. Is chronic lung disease in low birth weight

infants preventable? A survey of eight centers. Pediatrics

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5. Van Marter LJ, Allred EN, Pagano M, Sanocka U, Parad R,

Moore M, et al. Do clinical markers of barotrauma and

oxygen toxicity explain interhospital variation in rates of

chronic lung disease? Pediatrics 2000; 105(6):1194-201

6. Hutchison AA, Bignall S. Non-invasive positive pressure

ventilation in the preterm neonate: reducing endotrauma and

the incidence of bronchopulmonary dysplasia. Arch Dis

Child Fetal Neonatal Ed2008;93(1): F64-F68

7. Avery ME, Tooley WH, Keller JB, et al. Is chronic lung

disease in low birth weight infants preventable? A survey of

eight centers. Pediatrics. 1987;79(1):26–30

8. Morley CJ,Davis PG,Doyle LW et al. for the COIN Trial

Investigators. Nasal CPAP or intubationatbirthfor very

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9. F i n e r N N , C a r l o W A , e t a l .

SUPPORTStudyGroupoftheEuniceKennedy Shriver

NICHD Neonatal Research Network. Early CPAP versus

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2010;362(21):1970–1979

10. Ho JJ, Subramaniam P, Davis PG. Continuous distending

pressure for respiratory distress in preterm infants.

Cochrane Database of Systematic Reviews 2015, Issue 7.

Art. No.: CD002271.

11. Lista G, Fontana P, Castoldi F, Cavigioli F, Dani C. Does

sustained lung inflation at birth improve outcome of preterm

infants at risk for respiratory distress syndrome?

Neonatology 2011; 99 (1): 45-50.

12. Lista G, L. Boni, F. Scopesi, et al. Sustained lung inflation at

birth for preterm infants: a randomized clinical trial.

Pediatrics. 2015;135:e457-e464.

13. Verder H, Robertson B, Greisen G, Ebbesen F, Albertsen P,

Lundstrøm K, et al. Surfactant therapy and nasal continuous

positive airway pressure for newborns with respiratory

distress syndrome. N Engl J Med 1994; 331: 1051–5.

14. Verder H, Albertsen P, Ebbesen F, Greisen G, Robertson B,

Bertelsen A, et al. Nasal continuous positive airway pressure

and early surfactant therapy for respiratory distress

syndrome in newborns less than 30 weeks‘s gestation.

Paediatrics 1999; 103: e24.

15. Stevens TP, Blennow M, Myers EH, Soll R. Early surfactant

administration with brief ventilation vs. selective surfactant

and continued mechanical ventilation for preterm infants

with or at risk for respiratory distress syndrome. Cochrane

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CD003063.

16. Rojas MA, Lozano JM, Rojas MX, et al, Colombian

Neonatal Research Network. Very early surfactant without

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controlled trial. Pediatrics 2009; 123: 137-42.

17. Sandri F, Plavka R, Ancora G, et al. for the CURPAP Study

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with nCPAP in very preterm infants. Pediatrics. 2010;

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18. Dunn MS1, Kaempf J, de Klerk A et al, Vermont Oxford

Network DRM Study Group. Randomized trial comparing 3

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19. Rojas-Reyes MX, Morley CJ, Soll R. Prophylactic versus

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43


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418.

Invites Nominations forAward of Fellowship

The National Neonatology Forum (NNF) confers Fellowship (FNNF) to the members of the NNF who have made

outstanding contributions in the fields of Neonatology, Research, Development of Sub-specialties, Medical Publications

and Community Neonatology over and above the call of normal duty or due to position of the nominee.This year NNF

decided to accept one nomination of Staff Nurse who has made outstanding contribution in the fields of

Neonatology.

stThe last date for submit the nomination is 1 October 2017

For further details and Nomination Form please visit our website: www.nnfi.org

Dr. B.D. Bhatia Dr. Alok Bhandari

President Secretary

TM


44


Abstract

Introduction: Fracture of the femur in a newborn after caesarean section which is supposed to prevent this kind of traumatic delivery as a complication is rare but possible, at times extraction of baby becomes quite difficult even in caesarean deliveries specially if they arrive late at a facility.

Case Report: A female newborn 3.33 kg body weight was delivered from 28 year old primigravida by LSCS in view of fetal distress under spinal anaesthesia. Baby cried immediately after birth which did not require any resuscitative measures. Newborn had right thigh swelling immediately after birth, which was painful to touch. A radiograph of the right thigh revealed a fracture of the right femur shaft. Immediately, newborn was shifted to NICU for further management i.e. Immobilization with Pavlik harnessand Paracetamol drops three times a day for pain given after orthopaedics consultation. Patient responded well and was discharged on 7th day with advice of weekly follow up. At 2nd follow up at 6 weeks, healing fracture wasobserved on X-ray of right lower limb.

Conclusion: The case report has been brought out to analyse the fracture risk in caesarean section, which is quite rare. The requirement of a high index of suspicion in such deliveries, is thus of paramount importance.

Keywords: Caesarean Delivery, Fracture Femur, Immobilization

Introduction

Reported incidence of birth injuries is about 2% and 1.1%

in singleton vaginal deliveries of fetuses in a cephalic

position and in caesarean deliveries, respectively [1,2].

The most common fractures during normal vaginal

delivery occur in the clavicle, humerus and femur.

Caesarean section (CS) has been reported to reduce the

incidence of birth associated injuries to nearly none [3].

Femoral fracture during CS delivery is a rare

complication.

However, there are some reports of long bone fractures that

occurred during caesareans conducted to avoid such

complications [4]. The hypotheses of risk factors for

occurrence of such fractures remain conflicting.

Matsubara et al. [5] correlated the occurrence of long bone

fractures to only higher birth weight. Nadas et al. [6]

reported the correlation between occurrence of bone

fractures and caesarean section with breech delivery with

assistance and low birth weight.

The multicenter, randomized study of Hannah et al. [7]

showed that the fracture of long bones occurred in 0.1% of

cases during caesarean sections and 0.5% for vaginal

deliveries. So planning for a caesarean section reduces the

risk of fracture of long bones but does not eliminate the

possibilities [5,8-10].

The present study reports the first case of caesarean-

related right femur fracture in a neonate in our NICU since

its inception.

Case description

A female newborn 3.33 kg body weight was delivered from

28 year old primigravida by LSCS in view of fetal distress

under spinal anaesthesia. APGAR score was 8 at birth and

9 at 1 minute with normal vital and systemic examinations.

Operating surgeon gave a history of energetic traction but

no obvious sound of bony fracture heard during surgery.

Newborn had right thigh swelling immediately after birth

noticed by paediatrician, which was painful to touch. A

Right Femur Fracture during Caesarean Delivery

Rajesh Rai, Shital Kolhe, Kapil ShuklaDepartment of Pediatrics, DY Patil Medical College & Hospital,

Navi Mumbai, Nerul, Sector 05, Maharashtra , India. Pin -400706

Case Report

45


radiograph of the right thigh revealed a fracture of the right

femur shaft (Figure 1).There were no other fracture notice

elsewhere.

Immediately, newborn was referred to NICU for

management and to look for bleeding complications.

Laboratory analysis, including serum levels of calcium,

phosphorus and alkaline phosphatase, were normal. The

working diagnosis was fracture of the right femur shaft

without any complication as a result of birth injury.

Orthopaedic management included Immobilization and

Paracetamol drops three times a day for pain. Newborn

was continued on breast feeding. Patient responded well thand was discharged on 7 day with advice of weekly follow

ndups. At 2 follow up, healing fracture was observed on X-

ray of right lower limb (figure 2). At present, baby is fine,

growing well and fully immunized. A three month follow

up revealed complete healing of right femur without any

apparent shortening of the

limb (figure 3).

Discussion

There are very few reports

on bone trauma in LSCS.

In the medical literature,

there are only few articles

reporting cases of fractures

during caesarean section

[11-20]. This possibility,

as is reported in the

literature, is extremely

rare. Through the 60’s, 70’s

and 80’s, there have been

occasional repor ts of

f r a c t u r e o f f e m u r ,

depressed fracture of skull, fracture of tibia, radius and

rarely humerus and these were mostly in difficult breech

extractions [21]. During caesarean section, fractures

occurred fol lowing diff icul t del iver ies where

considerable traction was involved. Manoeuvres

employed during CS, poor delivery technique, uterine

incision and inadequate relaxation may cause these

injuries. The typical situation is when the breech is well

engaged in the pelvis or when a footling has descended into

the vagina. Research has shown that risk factors

speculated to be associated with femoral fractures during

CS are large fetuses, breech presentation, difficult

delivery, inadequate uterine relaxation, small incision,

twin pregnancies, osteogenesis imperfecta, prematurity

and osteoporosis [22].

The current lack of available data and the extreme rarity of

this complication do not detect an adequate and precise

maneuvering to avoid fracture of the femur. An

appropriate set of rules and procedures may prevent the

occurrence of such incident where these rules are

represented by an adequate analgesia, extraction by

exercising a delicate traction or by performing an uterine

incision which is sufficiently wide to allow a smooth

extraction. In this regard, it is recommended an extension

of the uterine incision rather than continue to exert traction

which become difficult and/or dangerous. The occurrence

Figure : 2 (at 6 weeks)

Figure: 3 (at 12 weeks)

Figure 1 (At birth)

46


of characteristic sound (crack) [5] may be regarded as an

important sign of breaking the femur of the newborn

during extraction. This finding should prompt and to carry

out further investigations such as X-rays of the lower limbs

of the newborn, all in accordance with the neonatologists.

These recommendations represent the process more

correctly for early detection of this complication, in order

to prepare an early treatment of the condition.

Several treatment modalities are described for fracture of

femur including immobilization, gallows traction, spica

cast, and Pavlik harness [7]. In our patient, immobilization

with Pavlik harness led to reunion of fractured shaft of

femur with no limb deformity and normal range of

movement with absence of crying on follow-up. Parents

were reassured and come for regular follow-up.

Lists of common fractures in complicated deliveries:

Clavicle 45.7%

Humerus 20%

Femur 14.3%

Depressed Skull fracture 11.4%

Conclusion

Caesarean delivery reduces the risk of causing a traumatic

injury of the newborn compared to vaginal delivery, but

does not eliminate this possible accidental complication.

Reporting of this case has been brought out to analyse the

fracture risk in caesarean section, which is quite rare.The

requirement of a high index of suspicion in such cases, is

thus of paramount importance. Counselling and

confidence building in mother is of utmost important to

keep them motivated to continue breast feeding. Exclusive

breast feeding also plays an important role for baby as well

as mother to recover from such type of trauma.

References

1. Alexander JM, Leveno KJ, Hauth J, et al. Fetal injury

associa ted wi th caesarean del ivery. Obste t r ics

&Gynecology 2006; 108:885.

2. Demissie K, Rhoads GG, Smulian JC, et al. Operative

vaginal delivery and neonatal and infant adverse outcomes:

population based retrospective analysis. British Medical

Journal 2004; 329:24.

3. Bistoletti P, Nisell H, Palme C, Lagercrantz H. Term breech

d e l i v e r y . E a r l y a n d l a t e c o m p l i c a t i o n s .

ActaObstetricaetGynecologicaScandinavica 1981; 60:

165-71.

4. Bangale RC. Neonatal fracture and caesarean section.

American Journal of Diseases of Children 1983; 137: 505.

5. Matsubara S, Izumi A, Nagai T, et al. Femur fracture during

abdominal breech delivery. Arch Gynecol Obstet.

2008;278:195–7.

6. Nadas S, Gudinchet F, Capasso P, Reinberg O. Predisposing

factors in obstetrical fractures. Skeletal Radiol.

1993;22:195–8.

7. M. E. Hannah, W. J. Hannah, S. A. Hewson, E. D. Hodnett, S.

Saigal, and A. R. Willan, “Planned caesarean section versus

planned vaginal birth for breech presentation at term: a

randomised multicentre trial,” Lancet, vol. 356, no. 9239,

pp. 1375–1383, 2000.

8. R. Jain and R. J. Bielski, “Fracture of lower femoral

epiphysis in an infant at birth: a rare obstetrical injury,”

Journal of Perinatology, vol. 21, no. 8, pp. 550–552, 2001.

9. A. O’Connell and V. B. Donoghue, “Can classic

metaphyseal lesions follow uncomplicated caesarean

section?” Pediatric Radiology, vol. 37, no. 5, pp. 488–491,

2007.

10. F. E. Campolat, A. Kose, and M. Yurdakok, “Bilateral femur

fracture in a neonate after cesarean delivery,” Archives of

Gynecology and Obstetrics, vol. 281, pp. 967–969, 2010.

11. H. Ehrenfest, Birth Injuries of the Child, Appleton-Century

Crofts, New York, NY, USA, 1922.

12. K. R. Kellner, “Neonatal fracture and cesarean section,”

American Journal of Diseases of Children, vol. 136, no. 9,

article 865, 1982.

13. A. D. Barnes and T. A. Van Geem, “Fractured femur of the

newborn at cesarean section. A case report,” Journal of

Reproductive Medicine for the Obstetrician and

Gynecologist, vol. 30, no. 3, pp. 203–205, 1985.

14. R. Vasa and M. R. Kim, “Fracture of the femur at cesarean

section: case report and review of literature,” American


15. J. T. Awwad, D. E. Nahhas, and K. S. Karam, “Femur

fracture during cesarean breech delivery,” International

Journal of Gynecology and Obstetrics, vol. 43, no. 3, pp.

324–326, 1993.

16. F. B. Cebesoy, O. Cebesoy, and A. Incebiyik, “Bilateral

femur fracture in a newborn: an extreme complication of

cesarean delivery,” Archives of Gynecology and Obstetrics,

vol. 279, no. 1, pp. 73–74, 2009.

17. R. Jain and R. J. Bielski, “Fracture of lower femoral

epiphysis in an infant at birth: a rare obstetrical injury,”


18. F. E. Campolat, A. Kose, and M. Yurdakok, “Bilateral femur

fracture in a neonate after cesarean delivery,” Archives of

Gynecology and Obstetrics, vol. 281, pp. 967–969, 2010.

19. Capobianco G, Virdis G, Lisai P, Cherchi C, Biasetti O,

Dessole F, Meloni GB. Cesarean section and right femur

fracture: a rare but possible complication for breech

presentation. Case reports in obstetrics and gynecology.

2013 Mar 6;2013.

20. Thakkar UG, Mishra VV, Vanikar AV, Agrawal RS, Kadam

47


PG. Fracture of shaft of left femur in a newborn delivered by

caesarean section. Sri Lanka Journal of Child Health. 2015

Mar 8;44(1).

21. John BM, Roy S, Gupta G, Wilson CG. A case of fracture in a

newborn delivered by caesarean section. Medical Journal

Armed Forces India 2004; 60: 194-5.

22. Morris S, Cassidy N, Stephens M, McCormack D,

McManus F. Birth associated femoral fractures: incidence

and outcome. Journal of Pediatric Orthopaedics 2002; 22:

27-30.

23. Rija L, Ansari T, Trikha V and Yadhav CS. Birth injuries in

caesarean sections: cases of fracture femur and humerus

following caesarean section. Nepal Medical College

Journal 2009; 11(3): 207-8.

48


Abstract

Neonatal osteomyelitis is a rare complication of late onset neonatal sepsis and Staphylococcus aureus is the most common causative microorganism reported everywhere. In osteomyelitis, pseudoparalysis owing to pain is common but few cases of true brachial plexus neuropathy have also been described in literature. Here, we present a neonate who manifested clinical features of Erb’s palsy on day third of life, later on diagnosed to be osteomyelitis, with isolation of unusual bacteria Acinetobacter species. Such an early onset of neonatal osteomyelitis, unusual presentation as Erb’s palsy and the unusual causative bacteria distinguishes this case from the previously reported series of neonatal osteomyelitis. This case highlights the consideration of humeral osteomyelitis as an important differential diagnosis of neonatal brachial plexus palsy.

Keywords: Acinetobacter, brachial plexus palsy, Erb’s palsy, neonatal osteomyelitis

Introduction

Neonatal osteomyelitis usually comes to clinical attention [1-5]in the late neonatal period and staphylococcus is the

[1-7]most common pathogen implicated. Here, we present an unusual case of neonatal Acinetobacter osteomyelitis, initially diagnosed as Erb’s palsy due to its presentation in early neonatal period, absence of local signs of inflammation and an initial negative sepsis screen.

Case presentation

A 20 year old primigravida at 35 weeks of gestation

delivered an 1800 grams girl baby in breech presentation

by emergency cesarean section in view of eclampsia.

There was a history of prelabour rupture of membranes

(PROM) for around 22 hours but there was no history of

antepartum maternal fever, foul smelling vaginal

discharge or urinary tract infection. Amniotic fluid was

meconium stained and the baby was born non-vigorous,

requiring endotracheal suction followed by positive

pressure ventilation for one minute. Apgar scores at 1, 2

and 5 minutes of age were 3, 5 and 8, respectively and the

baby was shifted to neonatal intensive care unit. Cord

blood documented metabolic acidosis which got corrected

by normal saline bolus alone. Thompson score on day-1 of

life was 11 as the baby was hypotonic, lethargic,

hyperventilating with absent Moro’s, suck and grasp

reflexes. Sepsis screen done on day-1 was negative. By

day-2 of life, respiration became normal, although the

baby continued to have hypotonia and absent reflexes. On

day-3, the generalized tone also started improving but the

left arm was still lying limp, adducted and internally

rotated by the side of trunk. There was no active abduction

of arm and the Moros’s reflex was asymmetrical. Left

elbow was kept in extension. Deep tendon reflexes in left

upper limb were absent. All the fingers of left hand were

kept in flexion symmetrical to the right hand, which

otherwise also happen in all normal newborns. Sensory

examination was normal as far as it could be examined.

Bilateral pupil reactions were normal. Left upper limb

paralysis observed in a systemically stable newborn

during early neonatal period, without any local sign of

inflammation, with an initial negative sepsis screen, made

An Unusual Presentation of Neonatal Osteomyelitis as

Erb’s Palsy with an Unusual Causative Pathogen

Priyanka Gupta*, Veena Devgan*, Dalip Kumar Bhagwani*, Monika Matlani**Department of Paediatrics* and Department of Microbiology**

North Delhi Municipal Corporation Medical College, Hindu Rao Hospital

Malka Ganj, Delhi-110007, INDIA

Corresponding Author:

Dr. Priyanka Gupta

Associate Professor

Hamdard Institute of Medical Sciences and Research

& HAH Centenary Hospital

New Delhi-110062, INDIA

Case Report

49


a possibility of Erb’s palsy. X-rays ruled out any clavicle or

humerus fracture and phrenic nerve palsy; and there were

no findings suggestive of osteomyelitis or septic arthritis.

Except for the persistence of palsy, the baby was fully

stable by day-7 of life on full enteral feeds. On day-9 of

life, baby developed features of septic paralytic ileus and

an abscess over right ankle (which was drained). Repeat

sepsis screen done on day-9 showed blood C-reactive

protein (CRP) of 422 mg/dL. Blood culture and pus culture

was sent and patient was started on injectable Amoxicillin

and clavulanic acid with Amikacin. Although the pus

culture did not pick up any micropathogen, blood culture

was positive for Acinetobacter species sensitive to

amoxicillin and clavulanic acid, and ciprofloxacin; and

resistant to amikacin, gentamicin, ceftazidime and

ceftriaxone. Blood culture was done by BACTEC and the

antibiotics sensitivity testing was done by Kirby Bauer

disc diffusion method. CSF findings were normal. X rays

of ankle over the site of abscess were normal. General

condition of the baby responded quickly within 36 hours of

antibiotics. After seven days of antibiotics, though the

baby did well, CRP fell down to a level of 250 mg/dL only.

A search for hidden abscesses like liver abscess and urine

infection was done, which was negative. Left limb

movements were improving but the CRP continued to

remain high 139 mg/dL even on day-14 of antibiotics i.e.,

day-23 of life. At this point of time, an X-ray was done,

which showed irregularity and lytic changes in the left

proximal humerus with local osteopenia, making a

diagnosis of osteomyelitis (Figure 1).

Figure 1: Left humerus with irregularity of proximal

metaphysis and lytic changes (day-23 of life)

Ultrasonography found irregular bony margins but no

increase in joint space. She was continued on intravenous

antibiotics for a total of three weeks, when her CRP fell

down to 29 mg/dL. By this time, all limb movements were

unrestricted. The baby was given amoxicillin and

clavulanic acid for three more weeks, i.e. a total antibiotic

treatment of six weeks. After six weeks of antibiotic

treatment, there was a radiological improvement as well as

the CRP came down to normal. As followed up clinically

till one year of age, the child did not suffer any disability.

Discussion

Nearly all series of neonatal osteomyelitis report the [1-5]presentation of patients after day seventh of life. To the

best of our knowledge, this is the first report of its kind in

which patient presented so early. Though not so in our case,

septic arthritis coexist with neonatal osteomyelitis in up to [5]76% cases.

In osteoarticular infections, pseudoparalysis of the [1, 3]extremities owing to pain or muscle spasm is common.

[8]It may thus be misdiagnosed as Erb’s palsy. Rare cases of

osteomyelitis/septic arthritis with true brachial plexus

n e u r o p a t h y h a v e a l s o b e e n r e p o r t e d . E x a c t

pathophysiology is unclear, which may be because of

extension of inflammation to the nearby structures,

occlusion of vasa nervosum due to vasculitis causing

ischemic neuropathy or alternatively nerve compression [4, 5]may occur. In our case, it could have been either a

misdiagnosed Erb’s palsy i.e. psedoparalysis; a true

brachial plexus neuropraxia as a complication of

osteomyelitis; or really a case of Erb’s palsy later on

developing osteomyelitis in the same arm.

The baby had three important risk factors for development

of osteomyelitis i.e., prematurity, low birth weight and [1, 4]PROM. Since the baby became symptomatic in early

neonatal period, prelabour rupture of membranes and

transplacental infection could be the only attributable

source of infection. Most common pathogen for

osteomyelitis in children in all age groups including [1-7]neonatal age is Staphylococcus aureus. With time,

streptococcus species, gram negative organisms

(Escherichia coli and Klebsiella pneumoniae) and

coagulase negative staphylocococcus have become other [1, 2, 3, 6, 7]important bacteria in the neonatal period.

Acinetobacter is a commonly isolated organism in [9, 10] infected warfare bone injuries but it has never been

reported in neonatal osteomyelitis. Acinetobacter

infection has emerged as an important pathogen in early

50


onset as well as nosocomial neonatal sepsis, reported [11, 12]incidence in India varying from 8.3-15.2%. Low birth

weight, prematurity and prelabour rupture of membranes

are three important identified risk factors for early onset [11-13]acinetobacter sepsis in newborns, all three of which

were present in our case too. To the best of our knowledge,

none of the reports of acinetobacter sepsis mentions

osteomyelitis as a manifestation or complication, making

this case unusual in this regard.

Total leucocyte counts and ESR frequently increase in

neonatal osteomyelitis but may be normal also in the initial

few days, as in our case. CRP, though not specific for

osteomyelitis, is a rapid indication of systemic [1, 4, 6, 7]inflammation and tissue damage. Radiographs have

a high specificity of 68-83% but poor sensitivity of 14-

54%. It may show soft tissue swelling and destroyed

fascial planes within few days after onset but in neonates,

even these findings may not be present as the fascial planes

are poorly defined and subcutaneous fat is lacking. Joint

effusions might be suspected if widening of joint space or

bulging of soft tissue is detected. Radiographic changes

usually lag by at least 2 weeks and the lytic changes usually

do not appear unless at least 50-75% bone matrix is [1, 6, 7]destroyed.

Treatment for osteomyelitis depends on fast and true

diagnosis made and a delay in treatment raises the risk of

complications. Intravenous antibiotics are given for 2-3

weeks and then switched to oral medicines for a total of 4-6 [1, 4, 6, 7]weeks. Neonatal osteomyelitis can even lead to

[1]complete joint destruction which fortunately did not

happen in our case.

Conclusion

This case reinforces the importance of humeral

osteomyelitis as an important and unforgettable

differential diagnosis of neonatal brachial plexus palsies,

consequences of missing which could be disastrous.

References

1. Kiechl-Kohlendorfer U, Griesmaier E. Neonatal

Osteomyelitis. In: Resch B (Ed). Neonatal Bacterial

Infection 2013; doi: 10.5772/54320. Available from:

http://www.intechopen.com/books/neonatal-bacterial-

infection/neonatal-osteomyelitis.

2. Potter CMC. Osteomyelitis in the newborn. The J Bone Joint

Surg 1954; 36(4): 578-83.

3. Knudsen CJM, Hoffman EB. Neonatal osteomyelitis. The J

Bone Joint Surg 1990; 72 (5): 846-51.

4. Nar MK, Kua KM, Wu CH. Septic arthritis and acute

osteomyelitis in early infancy. Clinical Neonatol; 6(2): 9-

13.

5. Mascarenhas A, Almeida C, Constantino C, Soudo AP,

Calado E, Vieira JP. Septic arthritis presenting as brachial

p lexus neurophaty. BMJ Case Rep 2011; doi :

10.1136/bcr.12.2010.3562.

6. Hatzenbuehler J, Pulling TJ. Diagnosis and management of

osteomyelitis. Am Fam Physician 2011; 84(9): 1027-33.

7. Calhoun JH, Manring MM, Shirtliff M. Osteomyelitis of the

Long Bones. Semin Plast Surg 2009; 23(2): 59–72.

8. Solebo JO, Keane MR, Obaro RO, Browne LM.

Osteomyelitis of head of humerus presenting as Erbs palsy

in a neonate. Eur J Pediatr 2004; 163(4-5): 262.

9. James WTE, Ciaran LB, Desmond TC, Craig SB.

Acinetobacter spp. in Gunshot Injuries. Emerg Infect Dis

2008; 14(1): 178–80.

10. Schafer JJ, Mangino JE. Multidrug-Resistant Acinetobacter

baumannii Osteomyelitis from Iraq. Emerg Infect Dis 2008;

14(3): 512–14.

11. De AS, Rathi MR, Mathur MM. Mortality audit of neonatal

sepsis secondary to acinetobacter. J Glob Infect Dis 2013;

5(1):3-7.

12. Shete VB, Ghadage DP, Muley VA, Bhore AV. Acinetobacter

septicemia in neonates admitted to intensive care units. J

Lab Physicians 2009; 1(2): 73-6.

13. Mishra A, Mishra S, Jaganath G, Mittal RK, Gupta PK, Patra

DP. Acinetobacter sepsis in newborns. Indian Pediatr 1998;

35(1): 27-32.

51


Abstract

Spontaneous umbilical cord hematoma is a rare life

threatening gestational event whose exact etiology still

remains unclear in spite of multiple hypotheses.Here, we

describe a term healthy newborn with spontaneous

umbilical hematoma thatotherwise had no risk factor for

the development of early neonatal sepsis. In spite of no

clinical evidence of chorioamnionitis, it being described

as one of the risk factor for the development of

spontaneous umbilical hematoma, baby was screened for

sepsis at six hours of age. Sepsis screen was found positive

and the neonate was treated with intravenous antibiotics

for five days in view of sepsis screen positive, blood culture

negative sepsis. Umbilical hematoma was the only indirect

clinical clue for neonatalsepsis in this case.

Keywords:Hematoma, neonatal sepsis, umbilical cord

Introduction

Umbilical cord hematoma is arare gestational event,

mostly commonly iatrogenic secondary to a procedure like

amniocentesis or cordocentesis (1-3). Spontaneous

umbilical cord hematomas are much more rare, reported

incidence variable ranging from 1 in 5500 deliveries to 1 in

12699 deliveries (1, 2, 4, 5). Around 50% of the affected

fetuses suffer in-utero mortality (2, 4, 6-8). Considering

this incidence of spontaneous umbilical hematoma and the

loss rate, the incidence in live births may be expected to be

around 1 in 11000 to 1 in 25400.

Several theories have been made behind the etiology ofa

spontaneous umbilical hematoma but the exact cause still

remains unclear. Here, we describe a term healthy neonate

born with spontaneous umbilical hematoma where there

was no clinical evidence of chorioamnionitis. There was

no other risk factor for development of umbilical

hematoma and early onset sepsis in the neonate. In view of

the hypothecation about chorioamnionitis also as one of

the risk factor for the development of spontaneous

umbilical hematoma, chorioamnionitis being an important

risk factor for early neonatal sepsis and easy possible

screening of early neonatal sepsis by cheap and easy

access laboratory tests; a sepsis screen was performed in

the neonate which was found to be positive warranting

treatment for sepsis screen positive neonatal sepsis.

Case presentation

A baby girl was delivered vaginally (without

instrumentation) after an uneventful labor to a 28 year old

booked second gravida mother at 40 completed weeks of

gestation.Antenatal period was uneventful with no history

of drug exposure, trauma, any invasive procedure like

amnio-or cordocentesis. All antenatal investigations

andsonograms were normal. Amniotic fluid was clear and

there was no history of any prolonged leaking per

vaginum, foul smelling vaginal discharge or maternal

fever. Fetal heart tracings were normal throughout the

labor.Apgar scores at 1 and 5 minutes were 8 and 9,

respectively. Baby was vigorous at birth and did not

require any resuscitative support.Two umbilical

hematomas were present at the fetal end of the cord, the

first one starting at the base of cord ~ 2 cm in length the

Spontaneous Umbilical Cord Hematoma;

An Unusual Clue for Early Onset Neonatal Sepsis

**Priyanka Gupta*, Abhinav Jain , Amlin Shukla*, Ashok Kumar Patwari*

**Department of Pediatrics* and Department of Radiology

Hamdard Institute of Medical Sciences and Research & HAH Centenary Hospital


Corresponding Author:

Dr. Priyanka Gupta

Associate Professor

Hamdard Institute of Medical Sciences and Research

& HAH Centenary Hospital


Email: [email protected]

Case Report

52


second one ~ 4 cm away from the base of the cord ~ 5 cm in

length [Figure 1].

Figure 1:Two umbilical hematomas at the fetal end of the cord,

the first one starting at the base of cord ~ 2 cm in length and the

second one ~ 4 cm away from the base of the cord ~ 5 cm in length

Rest of the umbilical cord was normal. Total cord length

was around 45 cm i.e., normal [9]. On cross section of the

cord, both arteries and one vein could be visualized.

Placenta and membranes were normal on gross

examination. Histopathology of placenta could not be

done. Birth weight was 2895 grams, length 49.5 cm and thhead circumference 34 cm (all more than 10 percentile for

gestational age i.e., normal). Vitals were stable without

any pallor and a normal systemic examination. Baby was

well but the cause of hemorrhage was unclear by now.

Thus, the baby was shifted to NICU for evaluation.Dry

cord care was done.Literature was reviewed and a possible

a s s o c i a t i o n o f u m b i l i c a l h e m a t o m a w i t h

chorioamnionitis/ funisitis was also found.Considering

the fact that the cord length was normal and the delivery

was non-traumatic, a search for the infection was

made.Blood reports of samples sent at 6 hours of life 3showedHb19.5 gm/dL, platelet count 1.62 lakhs/mm ,

3total leucocyte count 2400/mm , differential leucocyte 3count N L M E , absolute neutrophil count 1760/mm , 74 20 0 6

µESR 10 mm in first hour, qualitative CRP positive (1:3

dilution) i.e. around 18 mg/L, PT and APTT normal. As the

baby was otherwise well, she was bedded in with the

mother for routine care. After taking a blood culture,

intravenous cefotaxime and amikacinwas started in view

of sepsis screen positivity which was continued for five

days. Blood culture of the baby was found negative but

m o t h e r ’s u r i n e c u l t u r e s h o w e d p r e s e n c e o f 5Klebsiellaspps>10 CFU/mL sensitive to cefotaxime and

amikacin. There were only 2-3 pus cells/HPF on routine

microscopic examination of the mother’s urine.Neosporin

(neomycin, polymyxin-B sulphate and bacitracin zinc)

powder was also applied locally at the umbilicus for 5 thdays.Spontaneous cord shedding happened on day 6 of

life without any complication.Baby did well as last

followed up till one month of age.

Discussion

Bleeding in umbilical cord hematoma is usually venous in

origin (2, 4, 6). Extensive hemorrhage into the substance

of cord may surround all the three vessels and result in

compression of vessels with the most impact seen on the

venous flow. Most of the spontaneous cord hematomas are

associated with intrauterine death (4, 6-8), non-reassuring

fetal heart rate tracings, fetal distress and/orperinatal

asphyxia (4-6, 10, 11). Anemia in the newborn has also

been described due to umbilical cord hematoma (5). That

is why, if umbilical hematoma is detected in antenatal

ultrasound, it is an indication for continuous fetal

monitoring and possible emergency delivery of a viable

fetus. In the present case, antenatal and intranatal period

was uneventful and there was no anemia in the newborn.

Several hypotheses have been drawn behind the etiology

of spontaneous umbilical hematoma but the exact cause

still remains unclear. Short cord is described as one of the

most important risk factor for umbilical hematoma (3-6,

11, 12). Postmaturity is alsoone of the important risk factor

(3, 5, 8). Various other risk factors postulated are trauma

and traction while delivery (2, 4-6, 8), umbilical vessel

wall abnormality (3,7, 8, 10), association with umbilical

cord cysts (4), single umbilical artery (4), varix of cord

(12), non-specific inflammation of the cord (2, 6, 7),

chorioamnionitis (1, 3-5, 10) and fetal hemorrhagic

disease (2). In our case, histopathological examination of

the umbilical cord could not be done. However, based on

the gross examination of placenta/umbilical cord and the

clinical course, there was no obvious risk factor for the

development of umbilical hematoma. Although there was

no risk factor for early neonatal sepsis also in this neonate,

due to a hypothecation about possible association of

spontaneous umbilical hematoma with chorioamnionitis,

a sepsis screen was performed in the neonate, which was

found to be positive.

53


Conclusion

With the experience gained from this case, we may

conclude that all babies born with spontaneous umbilical

hematoma should be screened for early onset sepsis.

References

1. Skandhan AKP. Umbilical cord haematoma. Available

from: http://radiopaedia.org/articles/umbilical-cord-

haematoma (accessed on 16th October 2015).

2. Sutro WH, Tuck SM, Loesevitz A, Novotny PL, Archbald F,

Irwin GA.Prenatal observation of umbilical cord

hematoma.AJR Am J Roentgenol 1984; 142(4):801-2.

3. Goel P, Wanch M, Malhotra S, Kaur A, Nada R. Umbilical

Cord Haematoma : A rare cause of fetal death. JK Science

2002; 4(1): 43-4.

4. Towers CV, Juratsch CE, Garite TJ. The fetal heart monitor

tracing in pregnancies complicated by a spontaneous

umbilical cord hematoma.J Perinatol 2009; 29(7): 517-20.

5. Sizun J, Soupre D, Broussine L, Giroux JD, Piriou P,

Ventrillon E, Alix D, de Parscau L. Spontaneous umbilical

cord hematoma, a rare cause of acute fetal distress.Arch

Pediatr 1995; 2(12): 1182-3.

6. Larciprete G, Romanini ME, Arduini D, Cirese E,

Slowikowska-Hilczer J, Kula K. Umbilical cord segmental

hemorrhage and fetal distress.Int J Biomed Sci 2006; 2(2):

184-6.

7. Gualandri G, Rivasi F, Santunione AL, Silingardi

E.Spontaneous umbilical cord hematoma: an unusual cause

of fetal mortality: a report of 3 cases and review of the

literature.Am J Forensic Med Pathol 2008;29(2):185-90.

8. Clare NM, Hayashi R, Khodr G. Intrauterine death from

umbilical cord hematoma.Arch Pathol Lab Med 1979;

103(1): 46-7.

9. Stefos T, Sotiriadis A, Vasilios D, Tsirkas P, Korkontzelos I,

Avgoustatos F, et al. Umbilical cord length and parity—the

Greek experience.Eur J ObstetGynecolReprodBiol 2003;

107(1): 41-4.

10. Tonni G, Bonasoni MP, De Felice C, Rossi A, Tonni S.

Histopathological Findings in Spontaneous Hematoma of

the Umbi l ica l Cord: Severe Hypoxic- Ischemic

Encephalopathy in a Term Survived Newborn.Am J

Forensic Med Pathol 2015; 36(4): 254-6.

11. Seoud M, Aboul-Hosn L, Nassar A, Khalil A, Usta

I.Spontaneous umbilical cord hematoma: a rare cause of

acute fetal distress. Am J Perinatol 2001;18(2):99-102.

12. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse

DJ, Spong CY. Abnormalities of the placenta, umbilical cord

and membranes. In: Cunningham FG, Leveno KJ, Bloom

SL, Hauth JC, Rouse DJ, Spong CY, editors. Williams rdObstetrics. 23 ed. USA: The McGraw Hill Companies;

2010: 577-87.

Call for Free & Award Papers for

Presentation at Neocon [email protected]

The Scientific Committee invites delegates who wish to give a presentation during the NEOCON 2017 to be held from

December 8th-10th, 2017 at Hotel Lemon Tree, Gurugram, Haryana to submit the ‘Abstracts’ of their scientific studies.

Paper Category: Free Papers

The mode of presentation of free papers will be decided by the scrutinizing committee from amongst the abstracts received and

authors will be informed accordingly. The papers not taken for ‘Oral’ will be taken for ‘Poster’. If you want to send only for

poster please mark yor mail as POSTER ONLY

The text of the ‘Abstract’ should contain not more than 250 words. It should be structured as far as possible in the following

manner (Except Case Reports): (a) Introduction (b) Aims& Objectives (c) Material & Methods (including statistical methods

where relevant) (d) Results (e) Conclusions.

Instructions

1. Abstracts can be submitted via email ID: [email protected] as an attached word document

st 2. The deadline for sending in abstracts is 21 October,2017. This deadline will be strictly observed.

3. Abstracts or full papers sent by hardcopy will not be accepted.

4. Please quote your Central NNF membership number (mandatory).

5. Papers from non-members will not be accepted.

6. You must have acknowledgement of the receipt of paper from Central NNF for the papers submitted by you.

7. Please mention the category of paper according to Sub-specialty given below:

• Cardiology (CAR)

• Community Neonatology (CP)

• Endocrinology (ENDO)

• Gastroenterology (GE)

• Genetics (GENE)

• Growth & Development (GD)

• Hematology – Oncology (HO)

• Infectious Diseases (ID)

• Intensive Care (IC)

• Nephrology (NEP)

• Neurology (NEU)

• Nutrition (NUT)

• Respiratory (RESP)

54

• Miscellaneous (MISC)

• Innovation Paper (Separate category)

(B) Paper Category: Award Papers

Research papers are invited in following categories of awards.(Mandatory: Read the award rules before submission of

your paper, which may be obtained from the Central Office on request. The papers not submitted as per award rules will

be rejected.)

• NNF Gold Medal Award Paper

• Social Neonatology Gold Medal Award Paper

Instructions

1. The hard copy of the SUMMARY as well as FULL paper in 4 (FOUR COPIES) should be submitted to National

Neonatology Forum, 803, 8th Floor, A-9, Northex Tower, Netaji Subhash Place, Pitam Pura, Delhi-110034.

2. The first author should be less than 40 years as on January 01, 2017 (Please enclosed proof of the age)

3. Please quote your Central NNF membership number (mandatory).

4. Papers from non-members will not be accepted.

5. Only one paper for the award will be accepted from any one Life Member

6. The number of author should not exceed three. There is no age restriction for co-author.

7. Any author who has been recipient of the award is not eligible to present the paper in same category, however he /she can

be a co-author

8. The SUMMARY should not be more than 250 words. Also email copy of summary.

9. The FULL award paper should be in the style of “Journal of Neonatology”.

10. The title of the paper should be brief but adequately descriptive.

11. The text of the summary should be structured as far as possible into the following manner (a) Introduction (b) Aims &

Objectives (c) Materials & Methods (including statistical methods where relevant) (d) Results (e) Conclusions.

12. The papers not accepted for award competition will not be presented in any other category.

The last date for submission of award papers at the Central NNF Office (Hard Copy)along with soft copy in MS word stformat on a CD, is21 October 2017.

Notification of selection of Papers

The Scientific Committee will review abstracts and notification of acceptance / rejection will be sent to the first authors

indicated in the papers, by 1st week of November 2017. Please contact the NNF office at [email protected] if you do not

hear by this time.

Presentations

The Scientific Committee will consider abstracts for an ‘Oral’ or ‘Poster’ presentation. All presentations must be in English.

Best poster awards

All posters in the subspecialties mentioned in the list, will be considered for the “Best Poster Award”& “Best Innovation Poster

Award”. Judging will be based on scientific merit, visual presentation and the potential significance of the clinical research.

55

Detailed instructions for poster paper presenters will be sent after the selection process is complete.

Registration

Authors who have been notified that their abstract is accepted for oral or poster presentation will please note that they ought to

register for the NEOCON 2017, as per the prevailing fees at the time of registration.

Publication of papers

The papers that have been accepted for publication will be published in proceedings of NEOCON 2017. NNF holds all

publication rights including copyright unless otherwise intimated to the authors by NNF in writing.

Hon. Secretary General, National Neonatology Forum

803, 8th Floor, A-9, Narthex Tower, Netaji Subhash Place, Pitampura, Delhi-110034

Email: [email protected];

Website:http://www.nnfi.org

Telephones: (011) 27353535, Mobile: 8527453535

Dr. Alok Bhandari

Secretary

56

Bids are hereby invited for the “NEOCON 2019” which will be the th39 National Conference of National Neonatology Forum of India.

State NNF branches that wish to bid for NEOCON 2019

which may kindly note the following guidelines

• It had been resolved in the Executive Board Meeting that only those applications which are filled completely thaccording to the prescribed format and received by the Central NNF Office latest by 15 November 2017by

email or by post will be considered for the bid.

• Decision will be taken in the Governing Body. The bidding branches thus shortlisted will be informed of ththeir selection in General Body Meeting 2017 on 9 December 2017

• Each bidding branch has to send the DD of Rs 200,000with the bid. The hosting branch’s bidding amount of

Rs. 2 Lac will be accepted by Central NNF office and this mode of payment should be made in the name of

“National Neonatology Forum” payable at Delhi or through NEFT/RTGS as per bank detail given below:-

Account No. : 91191010001308, Name : Syndicate Branch : DTC Wazirpur, New Delhi-110035, IFSC Code: SYNB0009119, Account Name- National Neonatology Forum, Type of account - Current

• The format for submission of the bid is appended with this notice.

• The hosting branch should be registered with the Registrar of Societies, should have its own PAN and should

be filing its own Income Tax Returns. Central NNF, PAN cannot be used for NEOCON financial transactions.

Please submit along with the bid,

• Resolution passed by the branch,

• DD of Rs 2 Lac

• Copy of constitution,

• Copy of Registration certificate,

• Copy of the pan card,

• Members list and

• IT returns if any.

• Adherences to these guidelines are mandatory prior to bidding of Neocon.

• The venue of the conference should be able to accommodate at least 1000 delegates in the main conference hall

during plenary sessions and should be able to provide halls for at least 4 concurrent sessions of 250-350 person

capacity each.

• The venue should be located within 1-5 kilometres of hotels that can accommodate at least 1000 delegates.

• The venue should also have appropriate areas designated for scientific exhibition, inauguration function,

banquet(s), cultural event(s) and should have ample parking space.

• Rs 1000.00 for every registration has to be submitted every 3 monthly to the Central NNF and 30% of the profit

or Rs 1000 per registration ( whichever is more ) has to be submitted by one year of completion of the Neocon.

Dr. B.D. Bhatia Dr. Alok BhandariPresident Secretary

Bank Bank,

57

Format to be filled in while Inviting NNF National Conference

a) NNF City Branch / NNF District Branch inviting conference: ...............................................................................................

b) Does the hosting city have Medical College? YES / NO

If yes, is it Govt. Medical College / Private Medical College

c) Details of possible venue

Venue: ..................................................................................................................................................................................

Distance from Railway Station: ............................................................................................................................................

Distance from Airport: .........................................................................................................................................................

Main Hall sitting capacity: .................................................................................................................................................

Subsidiary Hall sitting capacity

Hall 1 ............................................ Hall 2 ............................................

Hall 3 ............................................ Hall 4 ............................................

Hall 5 ............................................ Hall 6 ............................................

d) Inauguration ceremony site & Sitting Capacity: ...................................................................................................................

Distance from conference venue: ........................................................................................................................................

e) Accommodation capacity in the host city (no. of beds available):

Hotel: Star ............................................ Non-star .................................................

Hostel ...................................................Guest House............................................

f) Transport connections to other parts of country:

No. of trains / day : ........................................................................................

No. of flights / day : .......................................................................................

g) Last National Conference held by host city (year): ........................................

Report submitted : Yes / No

h) Details of last Zonal / State / District / City Conferences held by host city:

Conference Year No. of delegates

1. ............................................ ............................................ ............................................

2. ............................................ ............................................ ............................................

3. ............................................ ............................................ ............................................

4. ............................................ ............................................ ............................................

I) We have read the guidelines and will abide by all the rules and regulations.

Signature Signature Signature

President Secretary Treasurer

Name & Address Name & Address Name & Address

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