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Maternal collapse and cardiorespiratory arrest Dr David Gabbott Consultant Obstetric Anaesthetist Gloucester, UK

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Page 1: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Maternal collapse and

cardiorespiratory arrest

Dr David Gabbott

Consultant Obstetric Anaesthetist

Gloucester, UK

Page 2: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 3: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Saving Mothers’ Lives:

Reviewing maternal deaths to

make

motherhood safer – 2006-2008

Tuesday 1st March 2011

Page 4: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 5: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Obesity

Diabetes

Hypertension

PET

Thromboembolism

Wound infection

Cardiac disease

Difficult airway

Venous access

Greater risk of PPH

Page 6: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

More than half of all the women who died from Direct or Indirect causes, for whom information was available, were either overweight or obese.

More than 15% of all women who died from Direct or Indirect causes were morbidly or super morbidly obese.

Page 7: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Resuscitation in Pregnancy

Two people to resuscitate

Early involvement of obstetrician and neonatologist

Cardiopulmonary arrest from non obstetric causes

- trauma

- cystic fibrosis

- anaphylaxis

- drug overdose

Page 8: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

CNST

Standard

1 2 3 4 5

Criterion

Organisation Clinical Care High Risk Conditions Communication Postnatal and Newborn Care

1 Risk Management Strategy

(Organisation)

Care of Women in Labour Severe Pre-Eclampsia Booking Appointments Referral When a Fetal

Abnormality is Detected

2 Risk Management Strategy

(Leadership)

Auscultation Eclampsia Missed Appointments Neonatal Resuscitation

3 Staffing Levels (Midwifery &

Nursing Staff)

Continuous Electronic Fetal

Monitoring

Operative Vaginal Delivery Clinical Risk Assessment

(Antenatal)

Admission to Neonatal Unit

4 Staffing Levels (Obstetricians) Fetal Blood Sampling Bladder Care Patient Information & Discussion Immediate Care of the Newborn

5 Staffing Levels (Anaesthetists &

Assistants)

Use of Oxytocin Perineal Trauma Maternal Antenatal Screening

Tests

Newborn Feeding

6 Guideline Development Caesarean Section Shoulder Dystocia Mental Health Newborn Security

7 Maternity Records Recovery Obstetric Haemorrhage* Clinical Risk Assessment

(Labour)

Examination of the Newborn

8 Incidents, Complaints & Claims Severely Ill Pregnant Women Venous Thromboembolism Handover of Care (Onsite) Support for Parents

9 Training Needs Analysis High Dependency Care Pre-Existing Diabetes Maternal Transfer Postnatal Care Planning

10 Skills Drills Vaginal Birth after Caesarean

Section

Obesity Admission to Emergency

Department

Postnatal Information

Page 9: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Maternal Emergency

Resuscitation Course

Page 10: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Adult ALS

Algorithm

Page 11: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

What is the same as non pregnant…

Rate and depth of chest compression

Drug doses e.g. 1mg adrenaline, 300mg amiodarone

Defibrillation energies

Single shocks

Time cycles

30:2 ratio for chest compression and ventilation

Page 12: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 13: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 14: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

What is the same as non pregnant…

Rate and depth of chest compression

Drug doses e.g. 1mg adrenaline, 300mg amiodarone

Defibrillation energies

Single shocks

Time cycles

30:2 ratio for chest compression and ventilation

Page 15: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Forty‐five women consented to

measurement of TTI at term. Post

partum measurements were made 6–8

weeks later on 42 of these women once

physiological changes had resolved.

Mean TTI was 91.3 (15.8) Ω at term and

91.6 (11.8) Ω 6–8 weeks after delivery.

The difference was not statistically

significant.

Do physiological changes in pregnancy change

defibrillation energy requirements?

J. Nanson, D. Elcock, M. Williams and C. D. Deakin

Br J Anaesth 2001; 87: 237–9

Page 16: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

What is the same as non pregnant…

Rate and depth of chest compression

Drug doses e.g. 1mg adrenaline, 300mg amiodarone

Defibrillation energies

Single shocks

Time cycles

30:2 ratio for chest compression and ventilation

Page 17: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Physiological changes

Page 18: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Airway

Airway obstruction

Increased risk of regurgitation

Tracheal intubation (difficult):

- large neck

- breast enlargement

- glottic oedema

- mucosal hyperaemia

- full dentition

- poorly applied cricoid

Page 19: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Prevalence of factors associated with difficult intubation in

early and late pregnancy. A prospective observational study

I Hayes, R Rathore, K Enohumah, N Salah, N Aslani, C McCaul

Dept of Anaesthesia, the Rotunda Hospital, Dublin, Eire

Difficult Airway Society Meeting, Cheltenham, Nov 2010

Page 20: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Sleep-disordered breathing and upper airway size in

pregnancy and post-partum

B. Izci, M. Vennelle, W.A. Liston et al, Eur Respir J 2006; 27: 321–327

Pregnant females had

significantly smaller upper

airways than nonpregnant

females at the oropharyngeal

junction when seated and

smaller mean pharyngeal

areas in the seated, supine

and lateral postures

compared with the

nonpregnant females.

Page 21: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Oxygen availability

Oxygen consumption = 250ml/min

Increased by 25% by full term

Available oxygen in non pregnant

Cardiac output x Hb conc x 1.34 x % saturation

5000 x 15/100 x 1.34 x 95/100

Total = 950ml

Approximately 4 minutes

Full term ~ 2-3 minutes

Page 22: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Apnoeic desaturation in pregnancy

Page 23: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Rates of neurologically favourable one month survival after chest

compression only CPR and conventional CPR in people with out of

hospital cardiopulmonary arrest witnessed by bystander

Ogawa T et al. BMJ 2011

Page 24: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Airway

Difficult airway box /

trolley

Page 25: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Easy to insert

Good seal pressures

Venting of gastric pressure and contents

May allow continuous chest compressions

Page 26: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

The use of ProSeal laryngeal mask airway in caesarean

section – experience in 3000 cases

BK Halaseh, ZF Sukkar, L Haj Hassan, ATH Sia, WA Bushnaq, H Adarbeh

Department of Anaesthesia, Farah Hospital, Amman, Jordan

3000 elective LSCS cases

Modified insertion with cricoid, gastric tube and laryngoscope

No failures

21 sore throat

Anaesthesia and Intensive Care 2010; 38: 1023-1028

Page 27: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 28: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 29: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 30: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 31: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Oesophageal insufflations with different SADs during positive pressure ventilation at (a) 40

and (b) 60 mbar.

Schmidbauer W et al. Br. J. Anaesth. 2012;109:454-458

Page 32: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 33: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Breathing

Diaphragmatic splinting

High inflation pressures may

be required

Reduced FRC and oxygen

reserve

Increased oxygen demand

Page 34: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Aufderheide, T. P. et al. Circulation 2004;109:1960-1965

Hyperventilation-Induced Hypoperfusion During Cardiopulmonary

Resuscitation

Page 35: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Coronary

perfusion

pressure

mm Hg

Leaning during chest compressions impairs cardiac output

and left ventricular myocardial blood flow in piglet cardiac

arrest Zuercher, Mathias MD et al. Crit Care Medicine 2010

Page 36: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Advanced pregnancy

Approximately 45% loss of chest wall

elasticity reduces intrathoracic

negative pressure

Page 37: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Waveform Capnography in CPR

Quantitative measurement of end tidal

CO2 may be a safe and effective non-

invasive indicator of cardiac output

during CPR and may be an early

indicator of ROSC in intubated

patients.

Low values of end tidal CO2

(<10mmHg) are associated with a low

probability of survival.

CoSTAR 2010

Page 38: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

The use of end-tidal CO2 monitoring

Arrows 1-8 fall in etCO2 as rescuer tires.

At 9 sudden rise indicating ROSC. Kalender Z. Resuscitation 1978;6:259-63

Page 39: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Circulation

IVC

Supine position causes caval compression

and reduced venous return

Page 40: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Caval Compression

May occur as early as 5th

month of pregnancy

Multiple pregnancy or

hydramnios increase risk

Even 45 degree tilt does not

relieve compression in all

mothers

30 - 50% of cardiac output via

IVC

Page 41: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Circulation

Displace uterus using:

- manual displacement

- left lateral tilt

Page 42: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Circulation

Displace uterus using:

- manual displacement

- left lateral tilt

Page 43: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Chest compression vs IVC compression

Unless the pregnant victim is on a tilting operating table, left

lateral tilt is not easy to perform whilst maintaining good quality

chest compressions

Start basic life support according to standard guidelines. Ensure

good quality chest compressions with minimal interruptions.

Manually displace the uterus to the left to remove caval compression.

European Resuscitation Council Guidelines for Resuscitation 2010

Page 44: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 45: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Quality of chest compressions performed by inexperienced rescuers in

simulated cardiac arrest associated with pregnancy

Seunghwan Kim, Je Sung You, Hye Sun Lee, Jae Ho Lee, Yoo Seok Park, Sung Phil Chung and Incheol Park

Resuscitation DOI: 10.1016/j.resuscitation.2012.06.003

Page 46: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 47: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Drugs

In light of potential inferior vena cava compression, it is advisable to ensure that venous access during cardiopulmonary resuscitation is above the diaphragm.

The circulation time of drugs given via a cannula placed in the lower limb may be delayed.

Page 48: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

IO access

Page 49: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Thrombolysis

The use of thrombolysis during

cardiopulmonary resuscitation is

now gaining momentum. There

are clear grounds for the use of

such clot busting drugs in

situations where thrombosis is

the primary cause of the cardiac

arrest e.g. massive pulmonary

thromboembolism (PTE).

Page 50: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Eclampsia

Page 51: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Magnesium overdose

Hypotension from vasodilatation

Reduced muscle power because of its effect at the neuromuscular junction

Uterine relaxation - bleeding

Reduced respiratory rate

Absent deep tendon reflexes

ECG changes e.g. prolonged P-R interval, wide QRS complex, conduction defects

Cardiac and respiratory arrest

Page 52: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Magnesium overdose

Treatment of magnesium overdose causing cardiac or respiratory arrest

Standard ALS procedures should be followed.

Calcium chloride 1g (10ml 10%) or calcium gluconate (30ml 10%)

Page 53: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Local anaesthetic toxicity

‘Hospital trust to pay £100,000 after

new mother died when painkiller was

attached to drip by mistake’

‘NHS trust facing prosecution after

new mother killed by epidural

anaesthetic mistakenly attached to

drip’

Page 54: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 55: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

In severe LA toxicity, the mother may have:

Sudden loss of consciousness

Convulsion

Cardiovascular collapse due to

- sinus bradycardia

- conduction blocks

- ventricular tachyarrhythmias

- asystole

Page 56: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Treatment

Start CPR using standard protocols

Treat arrhythmias using standard protocols but recognize that they may be very refractive to treatment

Prolonged CPR may be necessary; consider a cardiopulmonary bypass (if available) and early use of lipid emulsion

Page 57: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Lipid emulsion

CEMACH

AAGBI

Page 58: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Use of an ultrasound

machine if available is to

be encouraged. This will

allow determination of

concealed haemorrhage,

placental site, exclusion of

twins and visualisation of

foetal and maternal heart.

In skilled hands other

pathology may be

identified e.g. PE

Ultrasound in resuscitation

Page 59: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Course objectives

To achieve 4 standard TTE

views:

Parasternal long axis (PLAX)

Parasternal short axis (PSAX)

Apical 4 chamber (A4Ch)

Subcostal (SC)

Perform focused

echocardiography in an ALS

compliant manner

Page 60: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 61: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Perimortem LSCS

‘Perimortem caesarean

section is part of the

resuscitation procedure

in any woman who has

a cardiac arrest in the

second half of

pregnancy’.

CEMACH 2008

Page 62: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Greatly facilitates maternal resuscitation

Removes IVC compression

May allow the foetus to survive

Timing is essential (within 5 minutes of the

arrest)

May allow aortic compression / clamping

May allow internal cardiac massage by

surgeon

A Perimortem LSCS is performed because it:

Page 63: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Perimortem Caesarean delivery

Summary of postmortem caesarean

sections reported between 1900 and 1985

93% (57 /61) of surviving neonates were

born within 15 minutes of maternal death

70% of survivors were delivered within 5

minutes

Only 2 had neurological deficits

Katz et al Obstet Gynaecol 1986

Page 64: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Perimortem Caesarean section

Review 1985 until 2004 of perimortem

cesarean delivery:

38 cases

34 infants survived (3 sets of twins, 1 set

of triplets);

4 other infants survived initially, but died

several days after the deliveries from

complications of prematurity and anoxia.

Katz V.et al. Perimortem cesarean delivery: were our assumptions correct?

Am J Obstet Gynecol. 2005 Jun;192(6):1916-20

Page 65: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Perimortem Caesarean section

Time of delivery after maternal cardiac arrest was

available for 24 of 34 neonatal survivors.

n minutes

11 < 5

4 6 to 10

2 11 to 15

7 > 15

Page 66: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Woman Suspected of Cutting Baby

From Massachusetts Mom's Womb

Held on $2M Bail

Baby cut from murdered mother’s

womb found alive

Associated Press

Thursday, 30 July 2009

Page 67: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

CMACE 2011 – perimortem CS

Page 68: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 69: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Maternal cardiac arrest and perimortem

caesarean delivery: Evidence or expert-

based?

Sharon Einav, Nechama Kaufman and Hen Y. Sela

Resuscitation

Volume 83, Issue 10, Pages 1191-1200 (October 2012)

Page 70: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

94 reported cases (1980 – 2010)

Average age 30 yrs

Average gestational age 33 weeks

67% in hospital, 89% witnessed

54% (51/94) survived to discharge

Common causes - Trauma

- Cardiac disease

- Pre-eclampsia

- Amniotic fluid embolism

Page 71: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

PMCS performed in 76/86 viable pregnancy

Average time 16 minutes

4/76 within ‘5 minute’ rule

PMCS maternal survivors ~10 min

Non-survivors ~22 min

More ROSC and SHD with no PMCS

compared to those with PMCS (15/16 vs

39/72)

Neonatal survival 60% - mean time 14

minutes

Page 72: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary

Shockable

17.3%

Asystole

24.0%

PEA

474%

Page 73: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary
Page 74: Maternal collapse and cardiorespiratory arrest...now gaining momentum. There are clear grounds for the use of such clot busting drugs in situations where thrombosis is the primary