5/1/2015 SEPSIS SURVIVING SEPSIS CAMPAIGN HOW TO APPROACH THE POSSIBLE SEPTIC CHILD 2015 INFECTION CAN BE CONFIRMED BY:

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1 SURVIVING SEPSIS CAMPAIGN HOW TO APPROACH THE POSSIBLE SEPTIC CHILD 2015 Omer Nasiroglu MD Baptist Children s Hospital Pediatric Emergency Department SEPSIS IS A SYSTEMIC INFLAMMATORY RESPONSE SYNDROME (SIRS) IN THE PRESENCE OF SUSPECTED OR PROVEN INFECTION. International consensus on pediatric sepsis 2005 INFECTION CAN BE CONFIRMED BY: POSITIVE CULTURE, BLOOD, URINE, OR CSF TISSUE STAIN POLYMERASE CHAIN REACTION 1

2 SO WHAT IS SIRS? WIDESPREAD INFLAMMATORY RESPONSE THAT MAY OR MAY NOT BE ASSOCIATED WITH INFECTION. SIRS: -CORE TEMPERATURE >38.5 OR <36 C THE PRESENCE OF TWO OR MORE OF THE FOLLOWING CRITERIA (one must be abnormal temperature or leukocyte count): -LEUKOCYTE -ELEVATED OR DEPRESSED FOR AGE OR - >10 PERCENT IMMATURE NEUTROPHILS -TACHYCARDIA -MEAN HEART RATE MORE THAN 2 SD ABOVE FOR AGE -BRADYCARDIAMEAN HEART RATE <10 TH PERCENTILE FOR AGE -TACHYPNEA MEAN RR MORE THAN 2 SD ABOVE FOR AGE OR -MECHANICAL VENTILATION 2

3 SEVERE SEPSIS SEPSIS ASSOCIATED WITH: CARDIOVASCULAR DYSFUNCTION OR ACUTE RESPIRATORY DISTRESS SYNDROME OR DYSFUNCTION IN TWO OR MORE OTHER ORGAN SYSTEMS. SEPTIC SHOCK SEPTIC SHOCK IS CARDIOVASCULAR DYSFUNCTION THAT PERSISTS DESPITE THE ADMINISTRATION OF >60ML/KG OF ISOTONIC FLUID 3

4 -FLUID REFRACTORY -CARDIOVASCULAR DYSFUNCTION DESPITE AT LEAST 60ML/KG OF FLUID -CATECHOLAMINE RESISTANT SEPTIC SHOCK - DESPITE THERAPY WITH DOPAMINE >10 MCG/KG/MIN AND OR DIRECT CATECHOLAMINES EPIDEMIOLOGY -APPROXIMATELY 75,000 CHILDREN HOSPITALIZED FOR SEVERE SEPSIS EACH YEAR IN THE USA - THE INCIDENCE IS RISING SINCE MID-1990 AND IS AROUND 0.9 CASES PER 1000 POPULATIONS -RESPIRATORY AND BLOODSTREAM INFECTIONS ARE FOUND IN ALMOST 2/3 OF SEVERE SEPSIS -THE MORTALITY FROM PEDIATRIC SEPSIS HAS DECREASED FROM 97% TO APPROXIMATELY 4-10 % AND TO % IN PEDIATRIC SEPTIC SHOCK 4

5 RISK FACTORS NO IMMUNIZATION URINARY TRACT ABNORMALITIES GENETIC POLYMORPHISM AGE YOUNGER THAN ONE MONTH SERIOUS INJURY (TRAUMA OR PENETRATING WOUND) CHRONIC MEDICAL CONDITIONS HOST IMMUNOSUPRESSION LARGE SURGICAL INCISIONS IN-DWELLING VASCULAR CATHETERS MOST COMMON CAUSES: MRSA COAGULASE NEGATIVE STAPHYLOCOCCUS (NEWBORNS AND PATIENTS WITH INDWELLING VASCULAR CATHS) STREPTOCOCCUS PNEUMONIA GROUP B STREP IN NEONATES E COLI MOST COMMON CAUSES: PSEUDOMONAS AERUGINOSA KLEBSIELLA MENINGOCOCCUS GROUP A STREPTOCOCCUS OTHER BACTERIAS FUNGI- ESPECIALLY CANDIDA VIRUSES PARASITES 5

6 NEGATIVE CULTURE SEPSIS MAY INDICATE HOST RESPONSE TO BACTERIAL COMPONENTS SUCH AS ENDOTOXIN OR EXOTOXIN INFECTION THE NORMAL HOST RESPONSE TO INFECTION IS A COMPLEX PROCESS: ACTIVATION OF CIRCULATING AND FIXED PHAGOCYTIC CELLS GENERATION OF PROINFLAMMATORY AND ANTI- INFLAMMATORY MEDIATORS. SEPSIS = WHEN THE RESPONSE TO INFECTION BECOMES GENERALIZED AND INVOLVES NORMAL TISSUES REMOTE FROM THE SITE OF INFECTION THE HOST RESPONSE TO AN INFECTION IS INITIATED WHEN INNATE IMMUNE CELLS, PARTICULARLY MACROPHAGES, RECOGNIZE AND BIND MICROBIAL COMPONENTS PATTERN RECOGNITION RECEPTOR SUCH AS TOLL-LIKE RECEPTORS THE TRIGGERING RECEPTOR ON MYELOID CELL AND MYELOID ASSOCIATED RECEPTORS ON HOST CELLS 6

7 THE ENGAGEMENT OF THESE RECEPTORS ELICIT A SIGNALING CASCADE VIA ACTIVATION OF CYTOSOLIC NUCLEAR FACTOR KB THIS INDUCES ACTIVATION OF A LARGE SET OF GENES THAT ARE INVOLVED IN THE HOST INFLAMMATORY RESPONSE NEUTROPHILS BECOME ACTIVATED AND EXPRESS ADHESION MOLECULES THIS PROCESS IS HIGHLY REGULATED BY A MIXTURE OF PROINFLAMMATORY AND ANTI-INFLAMMATORY MEDIATORS SECRETED BY MACROPHAGES 7

8 SEPSIS OCCURS WHEN THE RELEASE OF PROINFLAMMATORY MEDIATORS EXCEEDS THE BOUNDARIES OF THE LOCAL ENVIRONMENT. WHY?? IS IT THE VIRULANCE OF THE BACTERIA? IS IT EXCESS OF PROINFLAMMATORY MEDIATORS? IS IT COMPLEMENT ACTIVATION? IS IT GENETIC SUSCEPTIBILITY? SEPSIS IS PRIMARLY A CLINICAL DIAGNOSIS - TOXIC OR ILL APPEARANCE - SIGNS OF DEHYDRATION - ALTERED MENTAL STATUS -DECREASED TONE -PETECHIAE - MENINGISMUS -RESPIRATORY DISTRESS - DISTENDED ABDOMEN -CELLULITIS - PROLONGED CAPILLARY REFILL 8

9 LABS: CBC WITH DIFF-RAPID GLUCOSE BLOOD GAS, LACTIC ACID, LFT, CHEM 7 PT, PTT AND D-DIMERS CULTURES (blood, urine e.g.) CRP, PROCALCITONIN AND PRESEPSIN (COMING SOON) IMAGING PROCALCITONIN THE PRECURSOR OF CALCITONIN (116 amino acid) UNDETECTABLE IN NORMAL PERSON (<0.5 ng/ml) IT GETS SYNTHESIZED AND SECRETED BY ALMOST EVERY CELL IN RESPONSE TO VARIOUS CYTOKINES AND LIPOPOLYSACCHARIDE IT IS CHEMOTACTIC PRESEPSIN SOLUBLE CD 14 SUBTYPE (64 amino acid) RELEASED BY SHEDDING FROM IMMUNE CELLS IT IS BELIEVED TO INTERACT WITH B AND T CELLS TO MODULATE IMMUNE RESPONSE 9

10 TREATMENT: SEPSIS TREATMENT ABC ALWAYS RAPID IV ANTIBIOTICS CEFOTAXIME AND VANCOMYCIN PENICILLIN ALLERGIC OR NEUTROPENIC PATIENTS: USE VANCOMYCIN WITH MEROPENEM OR CIPROFLOXIN SEVERE SEPSIS TREATMENT RAPID IV ANTIBIOTICS AND RAPID FLUID 10

11 TREATMENT OF SEPTIC SCHOCK: EARLY GOAL-DIRECTED THERAPY AGGRESSIVE IV FLUID THERAPY AND INOTROPS IN ADDITION TO IV ANTIBIOTICS WITH THE GOAL OF RESTORATION OF TISSUE PERFUSION CAPILLARY REFILL, QUALITY OF THE PULSES, MENTAL STATUS, URINE OUTPUT, BLOOD PRESSURE, LACTIC ACID, CENTRAL VENOUS OXYGEN SATURATION 11

12 DO NOT USE ETOMIDATE FOR INTUBATION IN SEPSIS REFERENCES Goldstein B, GiroirB, et al: international pediatric sepsis consensus conference. Pediatric Crit Care 2005;6:2-8 LaguT, Rothberg B M, et al: Hospitalizations, cost, and outcomes of severe sepsis in the United States 2003 to Crit Care Med 2012;40: LucignanoB, RannoS, et al: Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections in newborns and children with suspected sepsis. Journal of Clinical Microbiology 2011;49: Watson R S, CarcilloA j, et al: The epidemiology of severe sepsis in the children in the United States. Am J Respir CritCare Med 2002; 167: Dellinger R P, Levy M M, et al: Surviving sepsis campaign: International Guidelines for management of severe sepsis and septic shock: 2012 Crit Care Med 2013 ;41: Frantz S, ErtlG AND BauersachsJ: Mechanism of Disease. Toll=like receptors in cardiovascular disease. Nature Publishing Group 2007;4: Schwartz S R: Immunodeficiency and genetic defects of pattern-recognition receptors. N Engl J Med 2011;364:60-70 AssicotM, GendrelD, et al: High serum procalcitoninconcentrations in patients with sepsis and infection. The Lancet 1993;341: PoggC, Bianconi, et al: Presepsinfor the detection of late-onset sepsis in the preterm newborns Pediatrics 2015;135:68-75 Rivers E, NyugenB, et al: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345: Cruz T A, Perry M A et al: Implementation of goal-directed therapy for children with suspected sepsis in the emergency department. Pediatrics2011;127:e758-e766 RaimerL P, Han Y Y et al: A normal capillary refill time of <2 seconds is associated with superior vena cava oxygen saturation of>70 %. The journal of pediatrics 2011;158: Weiss L S, Fitzgerald C jet al: Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. CritCare Med 2014;34: Kumar A, Roberts D, et al.durationof hypotension before initiation of effective antimicrobial therapy is the 12