5/5/2010. Phil Bernard, MD. 2 week old presents to your office with fever to F HR 150 RR 40

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2 week old presents to your office with fever to 101.5 F HR 150 RR 40 BP not obtained obtained Sats 95% Phil Bernard, MD Baraff LJ, Bass JW, Fleisher GR, Klein JO, McCracken GH, Powell KR, et al.

Toxic kids later Non toxic appearance 0 28 days 3% SBI 1% meningitis 29 60 days 1.4% SBI 0.

1 2 week old presents to your office with fever to F HR 150 RR 40 BP not obtained obtained Sats 95% Phil Bernard, MD Baraff LJ, Bass JW, Fleisher GR, Klein JO, McCracken GH, Powell KR, et al. Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Pediatrics 1993;92:1 12. Toxic kids later Non toxic appearance 0 28 days 3% SBI 1% meningitis days 1.4% SBI 0.4% meningitis T cell lymphocytes non functional B cell lymphoctyes can t produce IgG s IgG levels rise greatly over the first few months of life 1 90 days RECTAL temperature > F (or 38 C) Overbundling is real recheck in 15 minutes If Mom reports rectal temperature believe it. 92% children hospitalized had subsequent fever 90 days 3 years > 102.2F (39 C) Viral RSV Influenza Enterovirus HSV (more later) 1

Bacterial Etiology Most common organisms Streptococcus pneumoniae 6% Niesseria menigitidis 15% Haemophilus influenza type B 2% Staphylococcus aureus 24% Staphylococcus epidermidis 19% Fungal

2 Bacterial Etiology Most common organisms Streptococcus pneumoniae 6% Niesseria menigitidis 15% Haemophilus influenza type B 2% Staphylococcus aureus 24% Staphylococcus epidermidis 19% Fungal infections 15%? 7 Meningitis Bacteremia Urinary tract infections Boston Rochester Philadelphia Peripheral white blood cell (WBC) count less than 20,000/microL CSF with WBC <10/microL UA <10 WBC per high powered field No infiltrate on chest radiograph if one was obtained 2

3 WBC <15,000/microL Band neutrophil ratio <0.2 UA <10 WBC/hpf and a negative urine Gram stain CSF <8 WBC/microL and a negative CSF Gram stain Chest radiograph lacking an infiltrate if one was obtained Stool without blood and few or no WBCs on the smear WBC 5,000 to 15,000/microL with an absolute band count <1,500/microL Urinalysis with <10 WBC/hpf and no bacteria seen Stool with <5 WBC/hpf if obtained Lee GM, Harper MB Risk of bacteremia for febrile young children in the post-haemophilus influenzae type b era. Arch Pediatr Adolesc Med. 1998; 152: Neonatal Group B strep Listeria monocytogenes E. Coli + GNR s Tx: Ampicillin + gentamicin vs. cefotaxime Pediatric Staphylococcus Niesseria menigitidis Streptococcus pneumoniae Tx: 3rd generation cephalosporin + Vancomycin (if they are SICK) 3

$fever in neonate 20 Warm shock MS, perfusion, flash cap refill with bounding pulses Cold shock MS, perfusion, cap refill > 3 sec and mottled cool extremities Fluid refractory dopamine$ resistant shock shock despite > 60 cc/kg over 1 hr and dopamine to 10 mcg/kg/min 2000 People/day develop Sepsis Mortality is ~ 30% Major category for admission to a Pediatric Intensive Care

resistant shock shock despite > 60 cc/kg over 1 hr and dopamine to 10 mcg/kg/min 2000 People/day develop Sepsis Mortality is ~ 30% Major category for admission to a Pediatric Intensive Care

4 Get a MANUAL DIFF < 1 month old = admission If you choose to treat with antibiotics Lumbar puncture if < 90 days Reflex U/A on any child < 2 years Don t consider otitis media source Of fever in neonate 20 Warm shock MS, perfusion, flash cap refill with bounding pulses Cold shock MS, perfusion, cap refill > 3 sec and mottled cool extremities Fluid refractory dopamine resistant shock shock despite > 60 cc/kg over 1 hr and dopamine to 10 mcg/kg/min 2000 People/day develop Sepsis Mortality is ~ 30% Major category for admission to a Pediatric Intensive Care Unit 11% of our patients admitted primary diagnosis 5/5/ % of children with sepsis also have shock 9 18% mortality Confirmed bacteria in ~ 75% of PICU patients Watson and Carcillo,

5 % 100% 80% Why are the outcomes changing? 60% 40% Mortality 20% 0% 1968 Univ Minn 1985 CNMC 1991 CNMC 1999 US Gram negative Sepsis Monoclonal antibody to LPS Anti Tumour necrosis factor alpha (TNF α) Antithrombin III (ATIII) Tissue factor pathway inhibitor (TFPI)

Oe Over 1/3 rd with cultures negative e 30 day

CO MORBIDITIES 31 Cohen, Nature, 2002 32

decreased from 31% to 26% Need to treat = 1 in

Pediatric use Cohen, Nature, 2002 33 N Engl J

ever in critically ill children Patients

6 EXPERIMENTAL Single genetic profile Blood borne Short term survival No mechanical ventilation Healthy REALITY Multiple polymorphisms Often with tissue infiltration Oe Over 1/3 rd with cultures negative e 30 day mortality Long term mech vent injury LOTS OF CO MORBIDITIES 31 Cohen, Nature, Activated Protein C Approved by FDA for severe sepsis in adults in Nov following PROWESS study Mortality decreased from 31% to 26% Need to treat = 1 in 16 patients Specifically not approved for Pediatric use Cohen, Nature, N Engl J Med 2001;344: Largest Pediatric trial ever in critically ill children Patients enrolled between Nov 2002 and April 2005 Ages newborn to 17 years Activated Protein C versus controls 5/5/

7 INCLUSION Infection proven or suspected New onset respiratory failure fil Sepsis induced cardiovascular dysfunction pressors EXCLUSION High risk of intracranial hemorrhage Imminent death 477 patients enrolled Study suspended after second planned interim analysis PEDS Severe hypovolemia Low cardiac output (hypodynamic) Most have High SVR Adults Less responsive to fluids CO maintained via tachycardia and ventricular dilation Circulatory collapse More volume More inotropy More responsive to ECMO 40 ADULT Incidence 751,000 cases/yr mortality 28.6% PEDIATRIC Incidence 42,000 cases/yr mortality 10.3% Etiology is changing immunizations Care is improving? Watson, et al. Am J Respir Crit Care Med 2003; 167:

120% 100% 80% 60% 40% 20% Mortality Very few good trials available Best Guess strategy Supportive Care 0% 1968 Univ Minn 1985 CNMC 1991 CNMC 1999 US Gram negative Sepsis 43 Neonatal Group B strep

cefotaxime Pediatric Staphylococcus Niesseria menigitidis Streptococcus pneumoniae Tx: Vancomycin + 3rd generation cephalosporin Herpes Simplex Virus Systemic Not subtle!

8 120% 100% 80% 60% 40% 20% Mortality Very few good trials available Best Guess strategy Supportive Care 0% 1968 Univ Minn 1985 CNMC 1991 CNMC 1999 US Gram negative Sepsis 43 Neonatal Group B strep Listeria monocytogenes E. Coli + GNR s Tx: Ampicillin + gentamicin vs. cefotaxime Pediatric Staphylococcus Niesseria menigitidis Streptococcus pneumoniae Tx: Vancomycin + 3rd generation cephalosporin Herpes Simplex Virus Systemic Not subtle! Fulminant and overwhelming Skin lesions in only 1/3 of patients Thrombocytopenia, Inc. LFT s, lymphocytic meningitis Meningoencephalitis Must have focal neurologic signs Bloody tap DOES NOT EQUAL HSV Enterovirus Myocarditis Meadows, TE, manuscript in progress Add Acyclovir only in cases with severe systemic infection, skin manifestations, or seizures KCH rate 1.3% of patients given Acyclovir had HSV; all had skin lesions or generalized seizures Candida (17% survival) Immunocompromised Treatment Fluconazole Amphotericin B 8

9 ER PICU modified from Carcillo patients 65 survivors 26 nonsurvivors Prism score 13 Prism score 26 Yong Y. Han, Joseph A. Carcillo, Michelle A. Dragotta, Debra M. Bills, R. Scott 54 9

urvival % Patient Su Patient survival vs whether shock was reversed 100 80 60 40 20 0 Shock reversed Persistant

resuscitation c/w PALS 100 80 60 40 20 0 Resuscitation Resuscitation c/w PALS NOT c/w PALS 55 56 Every hour

10 urvival % Patient Su Patient survival vs whether shock was reversed Shock reversed Persistant Shock urvival % Patient Su Patient survival vs. resuscitation c/w PALS Resuscitation Resuscitation c/w PALS NOT c/w PALS Every hour patient went without resuscitation increased mortality risk by 100% Every hour patient went without transfer increased mortality risk by 50% ScVO /5/ /5/

11 SvO 2 CVL catheters now available May be useful in pediatric sepsis One study performed Oliveria et al Reduction in mortality 39% to 12% Current practice guidelines Hgb 0f 10 mg/dl Multiple adult studies show liberal transfusion practices have higher morbidity and mortality 5/5/ Hebert multi center trial 648 hemodynamically stable children in PICU Randomized for transfusion threshold Hgb <9.5 Hgb < 7 Protocol suspended for hemodynamic instability, acute blood loss, severe hypoxemia 85% of patients had septic state 33% had multiple organ dysfunction 5% had septic shock Lacroix NEJM Transfusion requirements decreased significantly (98% vs. 46%) Primary and secondary endpoints equivalent New organ dysfunction Vasoactive drugs Not powered for mortality but they were equivalent Hydrocortisone WILL improve vasomotor tone and cardiac output 65 modified from Carcillo

12 Retrospective study of 6693 pediatric patients Multivariate analysis Overall mortality 24% Mortality * p< 0.05 Steroids No steroids Markovitz Pediatric Critical Care Med Don t necessarily intubate in the field (esp. if transport time is short) Landmark study by Gausche showed intubation in field trended towards worsening outcomes Success related to: the length of training, Supervised operating room and field experience Rapid sequence intubation (RSI) NOT recommended Instead Ketamine Atropine 69 VS Extubation Rates the same Post extubation stridor the same Caveat: keep cuff pressure < 20 mmhg New rule: cuff size = (age in years/4) + 3 ETT route is route of last resort? Accurate doses Vasopressin effective via ETT (but at what dose?) should we be even using it kids? Epinephrine i via ETT may give more effects and therefore may increase myocardial ischemia Newth

13 Bystanders Only Adult guidelines NOT FOR Pediatrics EMS providers Arrest from non cardiac origin AED s are now recommended for children 1 year and up Provide CPR before and immediately after shocking NO MORE SHOCK, SHOCK, SHOCK, Epi, SHOCK High dose epi is NOT recommended May be useful in rare circumstances (like blocker ingestion) Adult studies cooling may improve outcomes Neonatal studies cooling may improve outcomes Pediatric studies??? Consider cooling to C for patients who remain comatose following cardiac arrest Nitric oxide Continuous renal replacement therapy Extracorporeal Membrane Oxygenation DESPITE RUMOURS TO THE CONTRARY MOST OF OUR KIDS GO BACK TO THEIR HOMES! Golden Hour of Sepsis Multi disciplinary Multi tiered approach 78 13

Beyond the Reflex Arc: An Evidence-Based Discussion of the Management of Febrile Infants

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