Download Sepsis

Sepsis
Tara Benton, MD
Pediatric Critical Care Fellow
October 24, 2011
Objectives
 Definitions
 Epidemiology
 Microbiology
 Pathophysiology
 Guidelines for treatment
 Prevention
Sepsis
 “clinical syndrome that complicates severe
infection and is characterized by systemic
inflammation and widespread tissue injury”
Definitions
 SIRS (systemic inflammatory response syndrome)
 At least 2 of the 4 following criteria (abnormal temp or WBC
must be one of them)
 Temperature >38.5 or <36C
 Tachycardia (>2 SD above normal for age in absence of external
stimulus, chronic drugs or painful stimuli)
 OR otherwise unexplained persistent elevation over a 0.5-4 hr period
 OR for children <1 yr old: bradycardia, defined as a mean HR <10th
% for age
 Mean tachypnea>2 SD above normal for age or mechanical ventilation
for an acute process
 WBC elevated or depressed for age or >10% neutrophils
International Consensus Conference on Pediatric Sepsis 2005
Definitions
 Infection defined as a suspected or proven (by positive
culture, tissue stain or PCR test) infection caused by any
pathogen OR a clinical syndrome associated with a high
probability of infection
 Sepsis = SIRS + infection
 Severe Sepsis = SEPSIS + CV dysfunction OR ARDS OR 2
other organ dysfunctions
 Septic Shock = SEPSIS + CV dysfunction
International Consensus Conference on Pediatric Sepsis 2005
Definitions
 Shock
 Inadequate perfusion and oxygenation of the body and
its organs
 Delivery of substrate ≠ demand
Epidemiology
 Bacterial sepsis is the leading cause of medical
admissions to the PICU
 Worldwide, sepsis is the most common cause of death
in infants
 In 1995 Watson et al published a large population
based study evaluating severe sepsis - 0.56 cases per
1000 children (total of 40,000 cases each year)
 More common in infants especially low-birth-weight,
least common in 10-14yr
 Half of all patients in this study had underlying medical
conditions
 Respiratory infection and primary bacteremia
encompasses >40% of all causes
Epidemiology
 Mortality is consistent at ~10% across age groups
 Severity of illness does correlate with mortality (in
adults)
 SIRS – 7%
 Sepsis – 16%
 Severe Sepsis – 20%
 Septic Shock - 46%
Microbiology
 Most common pathogen overall is Staphylococcus of all types
 In the population study previously discussed, 18% of cases
overall and 26% of neonatal infections
 An international study from 2007, 44% of all cases were caused
by Staph
 Most common isolate overall is Staph aureus
 Other organisms noted in above studies: Streptococcus and
Pseudomonas aeruginosa
 Viral sepsis may be indistinguishable from bacterial sepsis
 HSV in neonates
Risk factors
 Genetic
 Study in adopted children by Sorensen et all in 1988 – more
likely to die from an infectious etiology if biologic parent died
from infection before age 50. Not associated with death from
infection in adoptive parents
 Polymorphisms identified in multiple inflammatory molecules
but unclear effect on host response
 Gender: M>F
Risk Factors
 Comorbidity
 Nearly half of all children with sever sepsis have an underlying
comorbidity (neuromuscular, CV, respiratory)
 Neoplasm associated with greatest number of sepsiis-related
deaths among all children
 In older children, CV conditions have the highest case fatality
rate of all comorbid conditions
 Risk of death increases with increasing number of organ
dysfunction
Risk Factors
 Environmental risk factors
 Surgical site infections
 1/3 most commonly reported infection (~15%)
 Contaminated procedure, surgery >2hrs, abd or thoracic procedure,
present of ≥ 3 discharge diagnoses
 Central venous lines
 Most often gram + bacteria (staph aureus, staph epi)
 GNR 21%
 Very young, chronically ill, poor nutritional status, loss of skin integrity,
neutropenia
 Endocarditis, Urosepsis, Hemodialysis, Osteomyelitis
Pathophysiology
Host inflammatory response
Massive and uncontrolled release of
proinflammatory mediators
Widespread tissue injury
Pathophysiology
 What the bacteria do to us:
 Depends on the bacteria
 Gram-negative
 Lipopolysaccharide (LPS) endotoxin – found in cell wall
 Rapidly triggers an inflammatory response from host
 Gram-positive
 Exotoxins (tetanus, diptheria, botulism)
 Endotoxin –like cell wall components (lipoteichoic acid (LTA), peptidoglycan)
 Soluble toxins (super antigens) – toxic shock syndrome
Pathophysiology
 What we do to fight the bacteria:
 First the pathogen is identified by our
innate immune system (macrophages,
neutrophils) by specific receptors (Tolllike receptors)
 These receptors trigger production of
proinflammatory gene elements
 Activation of innate immune cells and
enhancement of pathogen internalization
and intracellular killing
Pathophysiology
 What we do to fight the bacteria:
 Release of cytokines (TNF-α, IL-1) and
chemokines which modulate the
inflammatory response
 Of interest – anti-inflammatory cytokines are
produced as well (TGF-β, IL-1 receptor antagonist,
IL10 )
 Activation of adaptive immune system (T-
and B-lymphocytes)
 More cytokines released (able to produce
both pro- and anti-inflammatory)
 Activation of the endothelium results in
more cytokine release
Pathophysiology
 End organ results
 Endothelium
 Increase in vascular
permeability -> capillary leak
 Vasodilation
 Coagulation cascade
 DIC – both bleeding and
microvascular clots
 Myocardial dysfunction
 Temperature regulation
 Fever
Clinical presentation of Sepsis
 Classically early sepsis presents as:






Hyperdynamic and high cardiac output
Warm extremities
Flash cap refill
Widened pulse pressure
Fever
Ill appearing
 Progression to shock will have findings of end organ dysfunction
 Mental status changes (may just be irritability in infants)
 Grunting or other signs of impending respiratory failure
 Poor urine output
 Physical exam and history can give you clues to sites of infection
Clinical presentation of septic shock
Surviving Sepsis Campaign 2007 Guidelines for Pediatric Septic Shock
Treatment of sepsis
 Early recognition
 “Goal directed therapy” to restore tissue perfusion
 In 2002 – the first set of clinical practice parameters were
published
 Updated guidelines were published in 2007 and are what we
use today
Goal Directed Therapy – pediatric
patients
Goal Directed Therapy
Goal directed therapy - neonates
Goal directed therapy - neonates
Initial Antimicrobial Therapy
 As noted in the algorithm, antimicrobial therapy should be
initiated EARLY
 Complex decision for choosing antibiotics and history of
child is key
 Overall need to start broad spectrum
 Should cover MRSA for all children now
 If immunosuppressed or at risk like CF, should cover for
Pseudomonas
 Listeria monocytogenes and HSV coverage for infants <28 days
Initial Antimicrobial Therapy
 Children >28 days of age and normal hosts
 Vancomycin PLUS cefotaxime
 Consider clinda or metronidazole if suspected GI/GU source
 Children >28 days and immunosuppressed
 Vancomycin PLUS ceftazidime (or cefepime)
 Consider adding aminoglycoside like tobramycin
 For Penicillin allergic:
 Vancomycin PLUS meropenem
 For infants <28 days
 Typical is Ampicillin, Gentamicin, and Acyclovir
 Think about whether Vancomycin is needed for MRSA coverage
Initial Inotropic Therapy
 No one right answer for this
 Warm, vasodilated, no known cardiac disease -> NOREPI or




EPI
Cool, mottled -> DOPAMINE or EPINEPHRINE
Cardiac disease -> DOPAMINE OR EPINEPHRINE
If one isn’t working, add another
Think about vasopressin if not responding to the
catecholamines (Dopa, Epi, Norepi)
Summary of therapy
 Keep in mind goals up front












SvO2 70%
Perfusion pressure
CVP ~10-12
Follow lactate
Early antibiotics
Fluid
Fluid
Fluid
Inotrope
Additional Inotrope
Hydrocortisone
ECMO
ICU monitoring and continued care
 Intubation with lung protective mechanical ventilation if necessary
 Fluid removal
 Diruetics
 CRRT or PD
 Hemoglobin - >10gm/dl
 Now being debated
 Glycemic control – start insulin if necessary to keep glucose 100-
200
 Nutritional support utilizing enteral route if possible (transpyloric
if gastroparesis)
 Identifying source of infection and addressing this if possible
Prevention
 Vaccination
 Following recommendations for
reducing CLABSI
 Insertion bundle
 Meticulous sterile technique went
entering line
 GET THE LINE OUT
 Follow VAP prevention bundle while
intubated
 Remove all plastic as soon as possible
 Talk about lines/tubes/drains every day
on rounds and engage bedside nursing to
facilitate the above
THANK YOU