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TRANSCRIPT
8/5/2016
1
James Knapp, RN, CPNP-AC
Pediatric Critical Care Nurse Practitioner, Children’s Medical Center
Objectives
• Define shock and describe the physiologic changes
occurring in a shock state
• Review the classes and management of shock
• Describe the role of the nurse in assessment for
shock states
• Review goal directed therapy for sepsis and septic
shock
Shock
11 year old male
ED with ↑ abdominal pain
Started 3 days ago
Episodic
RLQ and peri-umbilical
T:39 HR:135 BP:90/45
Diaphoretic
Shuffles when he walks
Last voided before bed
Vomited 4 times this AM
VBG: 7.23/30/100/14/-13
Na: 133 K:4.5 Cl:90 CO2:12
Anion Gap: 20
What’s going on?
Is this child in shock?
What is shock?
What type of shock?
Why do you think so?
Why is this happening?
Shock: Definition
Inability of the circulation to deliver adequate oxygen and
nutrients to meet tissue demands
Cardiac Output = L/min of blood pumped from the LV
This is our “supply”
Supply (DO2) < Demand (VO2)
Do2 < VO2
What happens in this situation?
Hypoxia
Acidosis
Decreased clearance of byproducts of metabolism
Carcillo et al. (2002). Critical Care Medicine. 30(6)Figure 1. FACTORS AFFECTING OXYGEN DELIVERY
DO2
CaO2
CO
SV
HR
Oxygenation
Hgb
A-a gradient
DPG
Acid-Base Balance
Blockers
Competitors
Temperature
Drugs
Conduction System
Ventricular
Compliance
EDV
ESV Contractility
CVP
Venous Volume
Venous Tone
Metabolic Milieu
Ions
Acid Base
Temperature
Drugs
Toxins
Afterload
Influenced By
Influenced By
Influenced By
Oxygen
Delivery
Arterial
Oxygen
Content
Cardiac Output
= HR X SV
These alter
how O2 is
released to
tissues
Remember the
oxy-hemoglobin
dissociation
curve?
What factors can be affected by a shock state?
Intravascular volume
Pre-load
Vascular tone
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Oxyhemoglobin-Dissociation Curve
Left Shift =
hemoglobin holds on
tighter to oxygen
So could your cells be
starving for O2 with
normal sats?
Right Shift =
hemoglobin releases
oxygen more readily
Cardiac Output
Cardiac Output = Stroke Volume x Heart Rate
PreloadAfterload
Myocardial
contractility
How do infants and young children increase CO when needed?
How does blood pressure factor in to cardiac output?
From Guyton AC: Textbook of Medical Physiology, 6th ed. Philadelphia, WB Saunders, 1981
Cardiac Output
Arterial Pressure(BP = CO x SVR)
Causes of Inadequate CO
↓ Cardiac function
Decreased contractility
Myocardial Infarction
Toxic states of the heart
Cardiomyopathy
Obstruction to flow
Valvular dysfunction
Regurgitation of blood
Dysrhythmia
Factors ↓ venous return
↓ Blood volume
↓ Vascular tone
Obstruction to flow
Why maintain CO?
Cell metabolism and ATP production
Aerobic = 36 ATP
Anaerobic = 2 ATP + lactate
Protect blood flow to brain and heart
No significant constriction of cerebral or cardiac vessels
Auto-regulation of blood flow is excellent
Moderate ↓ in BP doesn’t significantly ↓ blood flow
Flow maintained SBP > 70 mmHg
Flow elsewhere may be ⅓ - ¼ normal
Shock
Critical State in Shock
Shock breeds more shock = “positive feedback”
Inadequate blood flow → tissue deteriorates, including heart
and vessels → further ↓ in cardiac output
Characteristics change with degree of severity
Non-progressive (compensated)
Progressive (uncompensated)
Irreversible (refractory)
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Non-progressive Shock
Not severe enough to cause its own progression
Negative feedback returns CO and BP to normal
Compensatory mechanisms are preserved
Baroreceptor reflex
CNS Ischemic response
Reverse stress-relaxation of circulatory system
Angiotensin and Vasopressin
Absorption of fluid
GI tract, interstitium, and ↑ thirst
Progressive Shock
Positive feedback further depresses CO
Important feature of progressive shock is progressive deterioration of the cardiac function and CO
Myocardial depression
↓ arterial pressure → ↓ coronary blood flow →weakens myocardium → further ↓ CO
Early: heart has tremendous reserve
May ↑ CO up to 300 – 400 %
Late: progressive myocardial depression
Progressive Shock
Exhaustion of compensatory mechanisms
Vasomotor center failure
Depletion of endogenous catecholamines
Inflammatory mediator release
Sludged blood
Acidosis
Increased capillary permeability
Cellular injury and death
Hypoxia/ischemia and reperfusion
Tissue necrosis
Irreversible Shock
Therapies ineffective
CO and BP may return to normal or near normal for short periods
Deterioration proceeds until death
Why?
Deteriorative changes have occurred
Cannot be overcome in the long term
When do we pass this critical point?
Depletion of intracellular high-energy compounds
ATP, creatine phosphate
Classifications of Shock
Hypovolemic
Hemorrhagic
Cardiogenic
Obstructive
DistributiveNeurogenic
Anaphylaxis
Septic
It is common for critically ill children to simultaneously experience more than one form of shock.
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Case Study # 1
• 18 month old male
• Diarrhea and vomiting for 2 days
• Poor PO intake last night
• Last wet diaper was this AM
• T: 101 F HR: 145 RR:40 BP: 90/50 O2 Sat:100%
• CBG: 7.27/35/65/18/-12
• What do you think?
Hypovolemic Shock
Leading cause of death in children
< 1 year due to diarrhea
Viral gastroenteritis most common cause
Bacterial causes of diarrhea
> 1 year due to hemorrhage from trauma
↓ intravascular volume ↓ Preload ↓ CO
Intestinal obstruction
Plasma loss via denuded skin (burns)
Dehydration
Blood loss
The Frank-Starling Mechanism
Importance of preload
Critical stretch point
no ↑ in contractility
may ↓ contractility
↑ sarcomere stretch from adequate filling increased contractile force
Hypovolemic Shock
Hemorrhage
Blood Volume = 70 – 80 cc/kg
Trauma #1 cause
Liver, spleen, mesentery, long bones, scalp lacerations
Post-surgical bleeding
GI bleeding
Esophageal varices, Mallory-Weiss syndrome
Coagulopathies
Hemorrhage and CO
~10% blood volume loss
No effect on arterial pressure or CO
Greater blood volume loss
↓’s CO then BP
35-45% blood volume loss
Arterial pressure falls to zero
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Hypovolemic Shock
Goals:
Restore intravascular volume quickly
Correct metabolic acidosis
Treat the underlying cause
Mainstay is FLUID
Degree of dehydration is often underestimated
Reassess often
Isotonic crystalloid is always a good choice
Colloid vs crystalloid
20-50cc/kg rapidly
If cardiac function is normal
Hyperchloremic metabolic acidosis
Vasopressors/Inotropes
Do not replace fluid!!
Co-existing septic/cardiogenic shock
Hemorrhagic Shock
Treatment
ABCs
Treat the cause
STOP the bleeding!
20-60cc/kg crystalloid
Type and cross ASAP
O- before cross matching is complete or type specific non-crossmatched blood products
Replace ongoing losses
Massive Transfusion Protocol
Weight/Age based ratio of blood products
PRBCs: Platelets, FFP, cryoprecipitate
Case Study # 2
8 day old female
Doing well at home until yesterday AM Tiring easily, especially with feeds
Increasingly listless
Vitals: HR: 195 (rest) RR: 74 BP: 80/45 O2 sat: 95%
Physical Exam Systolic murmur 2/6 heard best at 2-3rd ICS LSB
Peripheral pulses are +1 /Extremities cool and mottled
Color is pale/gray
What do you think?
Cardiogenic shock
Myocardial dysfunction
States of ↓ CO/non-cardiogenic shock
CHD or the sequelae of surgical repair
“Toxic states of the heart”
Cardiomyopathy
Myocardial ischemia Kawasaki disease, hypoxemia, anomalous coronary arteries
Myocarditis, pericarditis, endocarditis
Valvular disease
Dysrhythmia
Cardiogenic Shock
Management
Initial presentation can mimic
hypovolemic shock
Initial therapy is fluid challenge
If no improvement or worsens,
suspect cardiogenic shock
Need invasive monitoring
CALL INTENSIVIST and
CARDIOLOGIST
Improve cardiac output
Correct dysrhythmia
Optimize preload
Improve contractility
Reduce afterload
Decrease cardiac workload
Maintain normothermia
Sedation
Intubation and mechanical
ventilation
Correct anemia
Case Study # 3
• 13 year old female
• Respiratory Failure secondary to Pneumonia
• Mechanically ventilated
• PIP: 35 last hour
• Sedated and paralyzed
• Acute Change
• HR: 140 RR: 16 (vent) BP: 80/40 O2 sat:80%
• What do you think?
• What are you going to do?
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Obstructive Shock
Obstruction to flow
Compensatory ↑ SVR
Causes
Aortic stenosis
Coarctation of Aorta
Pulmonary embolism
Tension pneumothorax
Pericardial tamponade
Obstructive Shock
Initial presentation can mimic hypovolemic shock
Initial therapy is fluid challenge
Treat the cause
Pericardial drain
Chest tube
Surgical intervention
PGE
Case Study #4
5 yo male in MVC 2 days ago
Grade II liver laceration with stable H/H
Pulmonary Contusion on the vent
Right femur fracture in traction
Clindamycin and Unasyn
ND feeds while awaiting OR to fix femur
Pediasure
Called to bedside for rash and tachycardia
T: 37.9 HR: 145 RR: 35 (25 vent) BP: 100/40 O2 Sat: 93%
Hives on his trunk and beginning on his upper extremities
What do you think is going on? Could there be more than 1 type of shock going on?
Distributive Shock
Vascular capacity is greatly ↑ Normal blood volume is no longer adequate
Loss of vasomotor tone → vasodilatation → ↓ venous return
↓ filling pressure (preload)
Causes Deep general and spinal anesthesia
Brain damage to vasomotor center
Spinal cord injury above T1 Loss of sympathetic vascular tone
Septic shock, Anaphylaxis
Treatment Fluid replacement
Vasopressors
Anaphylaxis
Antigen – antibody reaction
IgE mediated degranulation of basophils and mast
cells
Release of histamine, mediators → vasodilatation → ↓
venous return
Dilatation of aterioles → ↓ arterial pressure
↑ capillary permeability
Loss of fluid and protein
Anaphylaxis
Treatment
Fluid
Histamine blockers
H1- Diphenhydramine
H2- Ranitidine
Dexamethasone
Reduce airway inflammation
SQ Epinephrine
Bronchodilatation
Vasopressors
Enhance venous return
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Case Study
Allergic Reaction
Medications investigated
Has not received any antibiotics recently
While looking his chart it is noted once that the child
has a history of “milk allergy”
Pediasure trophic feeds had been started about 7
hours earlier
Pediasure is a cow’s milk based formula
Case study #5
8 mo male presents to the PICU from heme-onc
History of neonatal leukemia
last course of chemotherapy 10 days prior to admission
Admitted to the floor 6 hours ago from clinic
Fever of 39.5C
Cultures sent
Received one dose of Zosyn, Amikacin and Vancomycin
40 minutes after Vancomycin
Mother noted him to be more lethargic
MET was called
On arrival to the PICU his vitals are as follows
T 38.9C HR 186 R 48 BP 88/29 O2 sats 94% on RA
What is the problem?
Septic Shock!
Stages of Sepsis
Mortality
7%
16%
20%
70%
SIRS
SEPSIS
SEVERE
SEPSIS
SEPTIC
SHOCK
MODS/DEATH
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Infection
A suspected or proven infection caused by any pathogen
Any + culture, tissue stain, or PCR
A clinical syndrome associated with a high probability of infection
Evidence includes + findings on clinical exam, imaging, or lab tests WBCs in normally sterile body fluid
Perforated viscus
CXR c/w pneumonia
Petechial or purpuric rash, or purpura fulminans
SIRS
Systemic Inflammatory Response Syndrome
Non-specific inflammatory response Trauma
Infection
Burns
Pancreatitis
Biochemical mediators → systemic inflammation response
Is this shock?
Not necessarily
If compensation is inadequate, then shock occurs
Unequal distribution of cardiac output
Compromised oxygen delivery to distal tissues
SIRS
> 2 of following
1 must be abnormal temp or leukocyte count
Core Temp >38.5 *C or < 36*C
Tachycardia
>2 SD above norm for age
Bradycardia in children < 1
RR >2 SD above norm for age
or need for CMV for an acute process
Leukocyte count elevated or depressed for age
or >10% immature neutrophils (bands)
Goldstein, et al. Pediatr Crit Care Med, 2005, 6(1) 2-8.
Sepsis
SIRS in the presence of or as a result of suspected or proven infection.
Documentation of a causative organism is not required by pediatric definitions
50% of cultures will show no growth
Severe sepsis
Sepsis plus one of the following:
Cardiovascular organ dysfunction or ARDS
OR
2 or more other organ dysfunction
Septic Shock
Sepsis and cardiovascular organ dysfunction
Isotonic fluid > 40 ml/kg in 1 hour
↓ in BP < 5th percentile, SBP <2 SD below norm
Need for vasoactive drugs to maintain BP
> 2 of the following
Unexplained metabolic acidosis
Base deficit > - 5 mEq/L
Arterial lactate >2 times normal
Oliguria: UOP < 0.5 ml/kg/hr
Prolonged capillary refill > 5 seconds
Core to peripheral temperature gap > 3° C
Inflammation
Immune system detects foreign antigen
Release of Cytokines by tissue macrophages: A call to arms Pro-inflammatory: TNF-a, IL-1, interferon-y
Limit damage, combat and eliminate pathogens, repair
Anti-inflammatory: IL-4, IL-10, soluble TNF-a receptors ↓ ability to process antigens and produce more inflammatory cytokines
Activation of the innate and adaptive immune systems
Activation of complement system and intrinsic pathway
Wall off the area to prevent spread of infection
And inflammation?
What happens when pro-inflammatory response overwhelms the limiting effects of the anti-inflammatory response?
Sepsis and septic shock
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Diagnosis and Treatment
of Septic Shock
Despite increased understanding of the role
of inflammation in severe sepsis, basic
treatment remains the same.
1. Examine and stabilize the patient
2. Diagnose and treat infection
3. Support organ function
Initial management is always directed at ABCs!
Spectrum of Cellular Dysfunction
HomeostasisNormal cell function
Death
Progressively increasing and widespread cellular dysfunction
Shock
SIR
S
Sep
sis
Sep
tic
Shock
Irre
vers
ible
shock
MO
DS
Infe
ctio
n
Progressively increasing and widespread inflammation
Recognition and Assessment
Identifying Acute Organ Dysfunction in
Severe Sepsis
Vital Signs
Physical Exam
CVP
End Organ Indices (Coags, LFTs, BUN/Cr)
Global Indices(Lactates, ABG, SvO2)
Invasive Cardiac Output Monitoring
Thresholds
Threshold rates Heart Rate MAP-CVP or MAP-IAP
Term Newborn 120-180 55 mm Hg
Up to 1 year 120-180 60 mm Hg
Up to 2 years 120-160 65 mm Hg
Up to 7 years 100-140 65 mm Hg
Up to 15 years 90-140 65 mm Hg
Estimate of Minimum SBP
Age Minimum systolic blood pressure (5th percentile)
0 to 1 month 60 mm Hg
>1 month to 1 year 70 mm Hg
1 to 10 years 70 mm Hg + (2 x age in years)
> 10 years 90 mm Hg
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Organ Dysfunction Criteria
Neurological
GCS < 11
Acute change in mental status
Hematologic
WBC elevated or decreased
Platelet count < 80K or 50% decline in past 3 days
INR > 2
Renal
Serum creatinine > 2 times upper limit of normal for age or 2-fold increase from baseline
Oliguria
Hepatic
Total bilirubin > 4 mg/dl
ALT 2 times upper normal for age
Cardiovascular
>40 cc/kg isotonic fluid in 1hr
Decrease in BP < 5th percentile for age or SBP < 2 SD for age
Need for vasoactive drugs
Heart rate above threshold rates
Two of the following
Metabolic acidosis
Elevated lactate
Prolonged capillary refill time
Core to peripheral temp difference >3o C
Respiratory
Increased WOB and distress
ALI and ARDS
PaO2/FiO2 ratio < 300 (< 200)
PaCO2 > 20 mmHg over baseline
Need > 50% oxygen tks > 92%
A Word About: Lab Data
Monitoring
Blood Gas
Acidosis
Oxygenation
ScvO2 vs. SvO2
Lactate
End-organ function
BUN/Cr
LFTs
Acute phase reactants
CRP
Sensitivity 63-95%
Specificity 40-91%
Serum amyloid A
Alpha 1-acid glycoprotein
Interleukins, TNF-a
Haptoglobin
WBC
Elevated or decreased
Immature neutrophils
“Bandemia”
“Left-shift”
Platelets
Initially rise then fall
Coags
PT/INR, PTT- elevated
Fibrinogen
Initially rises then falls
D-Dimer- elevated
What is going to change
first as we intervene?
Disseminated Intravascular CoagulationDisseminated Intravascular
Coagulation
From Dressler, DK. Patients with coagulopathies, In Clochesy JM, Critical Care Nursing, (1992)
Stimulation of coagulation
Intravascular
thrombosis
Hypoperfusion to
tissues and organsInability to
form a stable clot
Consumption of
coagulation factors
Secondary activation
of fibrinolysis
Release of
anticoagulants
bleedingbleedingIschemic damage
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Purpura fulminans
Goal Directed Therapy
Evidence-Based Management of Sepsis
Interventions to restore clinical end points
Warm extremities with normal capillary refill
Urine output > 1 ml/kg/hr
Normal heart rate, blood pressure, and pulses
Normal mental status
Timely administration of fluid resuscitation
Appropriate addition of vasopressors and inotropes as clinically indicated
Improve cardiac output and tissue perfusion
Timely administration of antibiotics
Fluid Resuscitation
Isotonic Crystalloid
Osmolality of fluids similar to serum osmolality
Normal saline, LR, Isolyte/Normosol
5% Albumin
Evidence comparing albumin to crystalloid is contradictory
20 ml/kg fluid boluses
Administered quickly over 5-10 minutes
Less in cardiogenic shock
Myocardial dysfunction
Commonly require 40-60 ml/kg in the first hour
May need more, up to 200 ml/kg
Fluid needs may continue for a prolonged period
Early and Aggressive Fluid Resuscitation
10-fold reduction in mortality
Purpura/meningococcal sepsis
Fluid resuscitation; inotropes/vasopressors in the ED
Mortality reduced (40% to 12%)
Aggressive fluid resuscitation, inotropes, blood
Goal to maintain ScvO2 > 70%
Reduced mortality from severe sepsis
Fluid resuscitation and antibiotics within first hour (ED)
Clinical Evaluation of Fluid Resuscitation
Goal is to improves preload and perfusion
Heart rate should decrease
Capillary refill improves
Urine output > 1 ml/kg/hr
How do we distinguish between fluid resuscitation and fluid overload?
What clinical signs indicate fluid overload?
Key is reassessment after each intervention
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Blood Products
Considered for patients with severe anemia
Hgb < 10 gm/dL and not hypotensive
Lower threshold is acceptable when shock resolved
> 7 g/dL
Sickle cell anemia
Goal to achieve ScvO2 > 70%
Platelets and FFP
Thrombocytopenia, coagulopathy or signs of bleeding
Not useful as replacement of isotonic crystalloid
Rapid infusion may lead to hypotension
Vasoactive kinins and high level of citrate in these products
Vasopressors and Inotropes
Why do we need these medications?
How can they help?
How do these medications work?
How are they different?
What are the specific clinical indications for each?
What do we have to watch for as adverse effects
of these medications?
How do we know they are helping?
Definitions
Inotrope:
Improves muscular contractility
Improves stroke volume
Chronotrope:
Increases heart rate
Generally a side effect of a medication, not an end goal
Vasopressor:
Affects the muscular constriction of capillaries and arteries
Vasodilator:
Causes muscles of the capillaries and arteries to dilate
Decreases afterload
Vasoconstrictor:
Causes muscles of the capillaries and arteries to constrict
Increases afterload
Factors Affecting Cardiac Output
Type Preload Afterload Contractility
Septic
early/
warm sepsis
late/
cold sepsis
Hemodynamic Changes in Sepsis
CO SVR MAP Wedge CVP
Septic: Early
or
Septic: Late
or
Norepinephrine A > β 0.02 – 1.5
mcg/kg/minVasoconstriction
Improves preload, MAP
Little change in HR
Epinephrine β > A
alpha
0.01- 0.5
mcg/kg/minInotropy, chronotropy
Improves contractility
↑ O2 consumption, HR
↓splanchnic flow
Vasoconstricts at higher
dose
Dopamine Dopa
receptor
release
of NE
A > β
< 5
mcg/kg/min
Vasodilation Dopaminergic
5 – 10
mcg/kg/min
Inotropy, chronotropy Beta-adrenergic, SV
> 10
mcg/kg/min
Vasoconstriction
Improves MAP, preload
Increases MAP,
improves preload
Dobutamine A > β 2 – 20
mcg/kg/min
Inotropy, chronotropy
Milrinone PDE III
inhibitor
0.25 – 0.75
mcg/kg/min
Inotropy, vasodilation Loading dose?
HypoTN toxicity
Phenylephrine Alpha 0.5 – 8
mcg/kg/min
Vasoconstriction
Improves MAP
Vasopressin V 0.01 – 0.04
units/min
Vasoconstriction of small
arterioles and capillaries
Restore catecholamine
sensitivity
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Adverse Side Effects
Epinephrine
Dysrhythmia
Tachycardia
Increased O2 consumption
Myocardium
Splanchnic circulation?
Vasoconstrictors
Dysrhythmia
Tissue hypoperfusion
Acidosis
Tissue necrosis
Vasodilators
Hypotension
Milrinone
Hypotension
Long half life
Dopamine
Dysrhythmia
Extravasation
Elevation
+/- warm compresses
Elevation
Phentolamine
Plastic Surgery consult
Peripheral administration
Supported by guidelines
Inotrope/Vasopressor Therapy
High CO state More common in pediatrics than adult septic shock
Low CO state Improve SV (fluid, vasopressors)
Fluid, Dopamine, norepinephrine, higher dose epinephrine
Improve contractility (inotropes) Dopamine, dobutamine, epinephrine, milrinone
Low SVR state Increase vascular tone (vasoconstrictors)
Norepinephrine, phenylephrine, vasopressin
High SVR state Improve peripheral circulation (vasodilators)
Milrinone if low CO state
Nitroprusside if CO normal
Role in Guideline Based Management
Achieving Therapeutic Endpoints
Blood Pressure
Heart Rate
Urine output
Perfusion
Laboratory diagnostics
Acid/base balance
Lactate levels
Mixed venous saturation (ScvO2) > 70%
Goal Directed Therapy
Evidence shows goal directed therapy
including the use of inotropes and vasopressors
as clinically indicated
to achieve therapeutic endpoints
markedly reduces morbidity and mortality of severe
sepsis and septic shock
Antibiotics
Timely administration of antibiotics is essential
Within the first hour of presentation
Each hour delay is associated with an increase in mortality
Inadequate antimicrobial use and in-hospital morbidity
Kollef, et al
Medical and surgical ICU patients
community-acquired or nosocomial infections
25.8% with inadequate antimicrobial therapy
↑ relative risk of death by 237%
Questions
How do I know which antibiotic to use?
What is the difference between bacteriostatic and bacteriocidal?
Why do certain drugs require levels?
Epidemiology of Pediatric Sepsis
Epidemiology of sepsis is affected by
Age
Site of infection
Immunocompetence
Vaccine status
Unimmunized
Under-immunized
Foreign Travel
Living conditions
A comprehensive history is essential
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Organisms In sepsis
Gram +: Staph aureus and Strep pneum
Gram -: E.coli, Klebsiella and Pseudomonas
Gram –ve organsims responsible for 62% of the
cases
Gram +ve responsible for 47%
Fungi in 16%
Epidemiology of Pediatric Sepsis
Pneumonia
Staph
Strep
Viral
Anaerobes
Aspiration pneumonia
Mycoplasma
Enterobacter
Bacteremia
Staph
Strep
Gram negative enteric
Klebsiella, E. coli
Enterococcus
Urosepsis
Gram negative enteric
E. coli, Klebsiella
Meningitis
Strep pneumoniae
H. influenza
Staph aureus
Immunocompromised
PCP
Fungal
Candida
Cryptococcus
Aspergillus
Antibiotics
Epidemiology based
Age based
Historical data
Radiographic and Lab data
Chronic health issues
Choices
Vancomycin
3rd gen cephalosporin
Antifungal?
Anaerobic or atypical?
Maternal/Delivery history
Environment
NICU environment and LOS
Choices
Ampicillin
Listeria
Gentamicin
3rd gen cephalosporin
Vancomycin?
Antifungal? Antiviral?
Infants and Children Neonates
After cultures are obtained when/if at all possible but should not be delayed
Double coverage may be necessary for certain organisms but is not preferable
Antibiotic use should be narrowed based on culture findings
Length of therapy is typically 7-21 days depending on site of infection
Source control is imperative
Antibiotic Therapy
Source Control Drainage of abscess
Debridement of infected or necrotic tissue
Removal of potentially infected device
Obstruction of urinary, biliary, or GI tract
Benefits Speeds resolution of clinical signs of severe sepsis
Shorten time to bacteriological resolution
Improve wound healing
Prevent further organ dysfunction
Decrease mortality
Summary
Epidemiology based
Age based
Historical data
Radiographic and Lab data
Chronic health issues
Choices
Vancomycin
3rd gen cephalosporin
Antifungal?
Anaerobic or atypical?
Maternal/Delivery history
Environment
NICU environment and LOS
Choices
Ampicillin
Listeria
Gentamicin
3rd gen cephalosporin
Vancomycin?
Antifungal? Antiviral?
Infants and Children Neonates
Immunocompromised: Zosyn + Aminoglycoside, consider Vancomycin
Guideline Recommendations
Antibiotics are administered within 1 hour of presentation
After cultures are obtained when/if at all possible
Should not be delayed
Double coverage may be necessary for certain organisms
Is not preferable
Immunocompromised patients, resistant organisms
Antibiotic use should be narrowed based on cultures
Length of therapy is typically 7-21 days
Pneumonia: 7-14 days
Bacteremia: 7-10 days
Urosepsis: 14 days
Meningitis: 21 days
Endocarditis: 21 days +
Resistant organisms, immunocompromised, osteomyelitis, and fungal infections may require longer therapy
Up to 6 weeks or longer
Source control is imperative
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Case Study #1
3 day old 36 week male
18 hours from ROM
Delivered via C/S
In NICU for feeding issues
Maternal history
GBS +
Treated 10 hours prior to delivery
Herpes +
No active lesions
Anti-viral therapy
Increased WOB, fatigues easily, and color/perfusion are poor
T: 37.6 HR: 192 RR:68 BP: 65/30 (40) O2 Sat: 95% (RA)
What do you want to do?
Fluid resuscitation
10 ml/kg crystalloid
Labs
CBG: 7.32/40/75/20/-6
Anion Gap: 14
Lactate: 4
Cultures
Blood, urine, CSF
Antibiotics
What are your choices?
Vascular access?
Reassessment
HR: 178 RR:70 BP: 68/35 (42) O2 Sat: 93%
What do you want to do now?
Case Study #1
10 ml/kg 5% Albumin
Intubation
ETT aspirate sent
6 ml/kg TV
PEEP 6
FiO2: 0.5
Sedation
UAC and UVC
CXR
Reassessment
HR: 165 O2 Sat: 97% BP: 66/35 (40)
Murmur is heard
Liver palpable at 4cm below RCM
UOP 0.7 ml/kg/hr
Cap refill 4 seconds
What is going on? What do we want to do about it?
Case Study #1
Is this child in shock?
What type of shock is it?
How do we figure that out?
Echocardiogram
Prostaglandins?
ABG: 7.38/44/99/20/-4
Lactate:4
CBC:
WBC: 17.5 Bands: 14
Platelets: 90
Hgb/Hct: 13/35
Coags
PT: 20.8
INR:2.3
PTT:55
Fibrinogen 120
D-Dimer: 5
What do you anticipate next?
Therapeutic end points in mind
Fluids?
Maybe later
Ongoing fluid needs
Inotropes vs vasopressors
Dopamine and Dobutamine
Blood products?
FFP
ARDS and PPHN
Inhaled NO
Renal insufficiency or failure
Steroids?
Hydrocortisone
Glucose control
Case Study #2
3 yo coming via transport from ETMC Longview
PMH: Previously healthy
Immunizations UTD
Respiratory distress
Fever to 39.5 ̊C
Blood and urine cultures obtained
Ceftriaxone given
20 ml/kg NS
Transport
Intubated due to WOB
Additional 20 ml/kg NS
During report en route
Additional 20 ml/kg NS
“He’s getting spots on his arms and legs”
What do you think is going on?
HR:160 BP:75/30 (45) O2 sat:95%
What are the priorities?
Therapeutic endpoints!!!
Fluid
Inotropes
Vascular access
Antibiotics: Vanc and Cefotaxime
Repeat cultures
Mechanical Ventilation
Lowest PIPs possible
Optimize PEEP and wean FiO2
Labs
ABG: 7.25/40/90/14/-16
Lactate: 8
WBC: 28 bands:19
Hgb:7.5 Hct:26 Plt: 90
CRP:28
PT: 35 INR:4 PTT:60 Fib:55
Case Study #2
What do we do?
Fluid
100 ml/kg NS total
Inotrope
Epinephrine
Blood products
FFP, platelets, PRBCs
Labs
Na: 148 K:5.4 ICa:0.98
ABG: 7.32/48/100/16/-4
Lactate:5
SvO2:
55 → 68% after blood
Cap refill 5 seconds
UOP 1 ml/kg/hr
Work toward therapeutic end goals
Fluid resuscitation
Titration of inotropes
Add vasodilator?
Monitor labs
ABG/VBG, lactates, electrolytes, coags, CBC
Calcium chloride
Blood products
What are we waiting for?
ARDS
Renal failure
Remove KCl
Reduce/monitor nephrotoxic drugs
Consider CRRT
Tissue loss from thrombosis
Wound management
References
Bateman SL, Seed PC. 2010. Procession to Pediatric Bactermia and Sepsis: Covert Operations and Failures in Diplomacy. Pediatrics, 126(1), 137-150.
Brierley J, et al. 2009. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med, 37(2), 666-688.
Cinel I, Opal SM. 2009. Molecular biology of inflammation and sepsis: A primer. Crit Care Med, 37(1), 291-304.
Cohen-Wolkowiez M, Benjamin DK, Capparrelli E. 2009. Immunotherapy in neonatal sepsis: advances in treatment. Neonatology and perinatology.
Dellinger, RP, et al. 2008. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med, 36(1), 296-327.
Goldstein B, Randolph A. 2005. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care med, 6(1), 2- 8.
Kreyman KG, et al. 2007. Use of polyclonal immunoglobulins as adjunctive therapy for sepsis or septic shock. Crit Care Med, 35(12) 2677-2685.
Malm G. 2009. Neonatal herpes simplex virus infection. Seminars in Fetal and Neonatal Medicine, 14, 204-208.
Marquardt DJ, et al. 2010. failure to recover somatotropic axis function is associated with mortality from pediatric sepsisinduced multiple organ dysfunction syndrome. Pediatr Crit Care Med, 11(1), 18-25.
Marshall JC, Reinhart K. 2009. Biomarkers of sepsis. Crit Care Med, 37(7), 2290-2298.
McWilliam S, Riordan A. 2009. How to use: C-reactive protein. Arch Dis Child Educ Pract Ed, 95, 55-58.
Nandyal RR. 2008. Update on Group B Streptococcal Infections: Perinatal and Neonatal Periods. J Perinat Neonat Nurs, 22(3), 230-237.
Nduku OO, Parillo JE. 2009. The Pathophysiology of Septic Shock. Crit Care Clin, 25, 677-702.
Parker MM, Hazelet JA, Carcillo JA. 2004. Pediatric considerations. Crit Care Med, 32(11), S591-S594.
van der Poll T, Opal SM. 2008. Host-pathogen interactions in sepsis. Lancet Infect Dis, 8, 32-43.
Posfay-Barbe KM, Wald ER. 2009. Listeriosis. Seminars in Fetal and Neonatal Medicine, 14, 228-233.
Short MA. 2004. Linking the Sepsis Triad of Inflammaation, Coagulation, and Suppressed Fibrinolysis to Infants. Advances in Neonatal Care, 4(5), 258-273.
www.survivingsepsis.org
Tidswell, M, et al. 2010. Phase 2 trial of eritoran tetrasodium (E5564), a Toll-like receptor 4 antagonist, in patients with severe sepsis. Crit Care Med, 38(1), 72-83.
Tsujimoto H, et al. 2008. Role of Toll-Like Receptors in the Development of Sepsis. Shock, 29(3) 315-321.
Watson RS, Carcilllo JA. 2005. Scope and epidemiology of pediatric sepsis. Pediatr Crit Care Med, 6(3), S3-S5.
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References
Balk RA, Ely EW, Goyette RE. 2004. National Initiative in Sepsis Education. Sepsis Handbook. 2nd edition. Thompson Advanced Therapeutics Communications and Vanderbilt University School of Medicine.
Evans TW, Smithies M. 1999. ABC of intensive care: Organ Dysfunction. British Journal of Medicine, 318, 1606-1609.
Goldstein B, Giroir B, Randolph A, et al. 2005. International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatric Critical Care Medicine, 6(1), 2-8.
Guyton AC, Hall JE. 2000. Textbook of Medical Physiology. Tenth edition. WB Saunders, Philadelphia.
Hildebrandt T, Mansour M, Al Samsam R. 2005. The use of steroids in children with septicemia: review of the literature and assessment of current practice in PICUs in the UK. Pediatric Anesthesia, 15, 358-365.
Leonard, C. Pediatric Shock: A practical approach to pediatric shock. 2004.
Rogers MC, Helfaer MA.1999. Handbook of Pediatric Intensive Care. Third edition. Williams & Wilkins, Baltimore.
Tabbutt S. 2001. Heart failure in pediatric septic shock: Utilizing inotropic support. Critical Care Medicine, 29(10), S231-S236.
Trimarchi T. Shock, Systemic Inflammatory Response Syndrome and Multiple Organ System Failure in Children. University of Pennsylvania School of Nursing. 2005.
Antibiotics
Beta-Lactams
Penicillins, Cephalosporins, Carbapenems
Interfere with bacterial cell wall synthesis
Bacteriocidal
Resistance occurs when organisms
Produce beta-lactamases
Keep antibiotics from attaching to the cell wall
Mutations alter bacterial cell wall target sites
Beta-lactamases keep the antibiotics from attaching
The receptor sites are changed
Penicillins
Natural Penicillins
Pen C, Pen V
High resistance
Strep, Staph, Enterobacter
Amino Penicillins
Ampicillin, Amoxicillin
Staph, Strep
Add sulbactam or clavulanate
Inhibit beta-lactamases
Unasyn, Augmentin
Anaerobic enteric organisms
Penicillinase resistant
PCNase producing Staph
Methcillin, Nafcillin, Oxacillin
Staph, Strep
Extended spectrum PCN
Beta-lactamase inhibitor
CarboxyPCN, Carbenicillin
MRSA, Klebsiella
Ticarcillin-clavulanate
Pseudomonas
Other Gram negative bacilli
Other Beta-Lactam Antibiotics
UreidoPCN
Piperacillin-tazobactam
Pseudomonas, Enterococcus
Carbapenems
Imipenem, Meropenem*
GPC, Gram negative bacilli, Anaerobes
+/- Pseudomonas
*Can cause myelosuppression
Monobactam
Aztreonam
Gram negative anaerobes, Pseudomonas
PCN allergic patients
Other Beta-Lactam Antibiotics
Cephalosporins
Generations 1-4
Gram + coverage with earlier generations
Increasing Gram – coverage with newer generations
Usually at expense of Gram + coverage
Except Cefepime
4th generation
StabLE to beta-lactamase activity
Resistance develops quickly
Cross-resistance to other beta-lactams Especially Serratia, Pseudomonas, Enterobacter
Empiric coverage in sepsis
3rd generation cephalosporin (plus vancomycin)
Immunocompetent infants (> 3 months of age) and children
Cefepime and Ceftazidime for Pseudomonas
1ST GEN: Cefazolin, Cephalexin
2nd GEN: Cefuroxime, Cefoxitin
3rd GEN: Cefotaxime, Ceftriaxone,
Ceftazidme
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Aminoglycosides
Amikacin, Gentamicin, Tobramycin, Streptomycin, Netilmycin
Gram – organisms (E. coli, Klebsiella, Serratia)
Pseudomonas
Synergy for MRSA
Usually combined with other drugs due to poor tissue penetration
MIC = Mean Inhibitory Concentration
The concentration in vitro where colony growth is inhibited
Bactericidal with serum levels > MIC
Goal is to achieve serum levels 10-12 x the MIC
Nephrotoxicity, Ototoxicity
Therapeutic drug monitoring
Attain desired serum level
Prevent tissue accumulation which is associated with toxicities
Dose is increased in patients with increased Volume of Distribution
Dose is decreased in patients with decreased renal function
Glycopeptides
Vancomycin
Interferes with cell wall synthesis
Bacteriostatic
Gram + staph, MRSA, CONS, Gram + anaerobes, Streptococcus, Enterococcus, Corynebacterium
No Gram - coverage
Nephrotoxic
Therapeutic drug monitoring
Increasing resistance
Treatment of choice for Clostridium difficile
Oral route is preferred
Teicoplanin
Similar to vancomycin
Active against VanB and VanC strains of VRE
Most outbreaks of VRE are caused by strain VanA
Oxazolidinones
Linezolid
Bacteriostatic
Enterococcus, Staphylococcus
Bacteriocidal
Streptococcus
VRE, nosocomial PNA cause by Staph aureus (MRSA) or
PCN resistant strains of Strep, skin infections, CAP
caused by susceptible Gram +
Myelosuppression if used > 2 weeks
Fluoroquinolones
Generations 1-5
Ciprofloxacin, Moxifloxacin, Ofloxacin, Levofloxacin
Bactericidal
Interfere with bacterial DNA synthesis
Hospital acquired infections
Pneumonia, UTI
Gram + and Gram – organisms
Pseudomonas, resistant Strep, Bacteroides
Adverse side effects
CNS toxicity (seizures)
Tendonitis
QTc prolongation, dysrhythmia
Macrolides and Azalides
Macrolides
Erythromycin
Legionella, Mycoplasma
Clarithromycin
Extends coverage to Gram +, H. influenzae, Moraxella
PCN allergic patients with Gram + infection
Azalides
Azithromycin
Similar to clarithromycin, longer half-life
GU pathogens
Chlamydia, Neisseria gonorrhea
Mycoplasma
Many drug-drug interactions through CYP450 interactions
Bacterial protein synthesis inhibitors
Bacteriostatic
Lincosamide
Clindamycin
MRSA, Strep pneumococcus, anaerobes
Bacterial protein synthesis inhibitor
Bacteriostatic
Adverse effects
C. difficile is uniformly resistant and causes overgrowth
Pseudomembraneous colitis
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Chloramphenicol
Strep, Gram – anaerobes, some Staph
Bacteriostatic
Restricted to severely ill without other options
Meningitis in patients with PCN allergy
Adverse effects
Idiosyncratic aplastic anemia
Hemolysis in patients with G6PD
Many hypersensitivity reactions
Folic Acid Antagonists
Sulfonamides
Gram + and Gram - organisms
Hypersensitivity reactions
Stevens-Johnson disease
Pancytopenia
Trimethoprim
Trimethoprim-sulfamethoxazole (Bactrim)
Some Gram + organisms (including MRSA)
Gram – enteric organisms causing UTI
E. coli, Enerobacter, Klebsiella
Bacteriostatic
Aplastic anemia, thrombocytopenia
Antifungals
Azoles
Fluconazole
Candida in non-HIV
Itraconazole
Candida, Aspergillus
Ketoconazole
Candida
Voriconazole
Aspergillus
Echinocandins
Caspofungin
Invasive Aspergillosis
Sysemic candidiasis
Those resistant to azoles
Amphotercin B
Liposomal Amphotercin B
Systemic fungal infections
Immunocompromised
Systemic SE in up to 90%
HA, myalgia
Fever
Hypotension, N/V
Nephrotoxic
Causes distal RTA