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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4

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

8/5/2016

7

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

8/5/2016

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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