H. Michael Ushay

Mortality rates in pediatric septic shock with and without multiple organ system failure

Objectives To determine the current mortality rates for pediatric patients with septic shock and the frequency and outcome of associated multiple organ system failure. Design Retrospective chart review. Setting Multidisciplinary pediatric intensive care unit. Patients Children age 1 month to 21 yrs admitted to the pediatric intensive care unit from January 1, 1998, to December 31, 1999, with a diagnosis of septic shock. Interventions None. Measurements and Main Results A database of all admissions to the pediatric intensive care unit was queried, and cases with diagnoses of sepsis and septic shock were reviewed. The final study cohort consisted of 96 episodes of septic shock in 80 patients. Septic shock was defined as a clinical suspicion of sepsis manifested by hyperthermia or hypothermia accompanied by hypotension and/or alteration in perfusion. Multiple organ system failure was defined by established criteria. Data were analyzed by using Fisher’s exact test. The overall mortality rate for the study cohort was 13.5%. There were differences in case mortality rates between patients requiring one inotropic agent (0%) and patients requiring multiple inotropic agents (42.9%), between oncology patients who had undergone bone marrow transplantation (38.5%) and oncology patients without bone marrow transplantation (5.5%), and between patients with multiple organ system failure (18.6%) and those without multiple organ system failure (0%); p < .05. There did not appear to be differences in the case mortality rates between oncology and nononcology patients or among patients with varying degrees of neutropenia. Conclusions The mortality rate in pediatric septic shock is lower than has been previously reported. Oncologic illness in the absence of bone marrow transplantation does not appear to be associated with an increased mortality rate in children with septic shock. Bone marrow transplantation patients have an increased mortality rate compared with other patients with septic shock. Mortality from septic shock occurs most frequently in the context of multiple organ system failure.

PHARMACOLOGY OF PEDIATRIC RESUSCITATION

The resuscitation of children from cardiac arrest and shock remains a challenging goal. The pharmacologic principles underlying current recommendations for intervention in pediatric cardiac arrest have been reviewed. Current research efforts, points of controversy, and accepted practices that may not be most efficacious have been described. Epinephrine remains the most effective resuscitation adjunct. High-dose epinephrine is tolerated better in children than in adults, but its efficacy has not received full analysis. The preponderance of data continues to point toward the ineffectiveness and possible deleterious effects of overzealous sodium bicarbonate use. Calcium chloride is useful in the treatment of ionized hypocalcemia but may harm cells that have experienced asphyxial damage. Atropine is an effective agent for alleviating bradycardia induced by increased vagal tone, but because most bradycardia in children is caused by hypoxia, improved oxygenation is the intervention of choice. Adenosine is an effective and generally well-tolerated agent for the treatment of supraventricular tachycardia. Lidocaine is the drug of choice for ventricular dysrhythmias, and bretylium, still relatively unexplored, is in reserve. Many pediatricians use dopamine for shock in the postresuscitative period, but epinephrine is superior. Most animal research on cardiac arrest is based on models with ventricular fibrillation that probably are not reflective of cardiac arrest situations most often seen in pediatrics.

Serial Measurement of Amino-Terminal Pro-B-Type Natriuretic Peptide Predicts Adverse Cardiovascular Outcome in Children With Primary Myocardial Dysfunction and Acute Decompensated Heart Failure.

Objectives: In children, elevated amino-terminal pro-B-type natriuretic peptide levels are associated with impaired heart function. The predictive value of serial monitoring of amino-terminal pro-B-type natriuretic peptide levels in acute decompensated heart failure is unclear. Design: Prospective observational study. Setting: Single, tertiary referral pediatric critical care unit. Patients: Patients aged 0-21 years with primary myocardial dysfunction and acute decompensated heart failure. Interventions: Amino-terminal pro-B-type natriuretic peptide levels were obtained on enrollment, day 2, and day 7. Clinical, laboratory, and imaging data were collected on enrollment. Adverse cardiovascular outcome was defined as heart transplant, ventricular assist device placement, extracorporeal membrane oxygenation, or death at 1 year after admission. Aminoterminal pro-B-type natriuretic peptide levels and the percent change from day 0 to day 2 and day 0 to day 7 were calculated and compared between those with and without adverse cardiovascular outcome. Measurements and Main Results: Sixteen consecutive patients were enrolled. Adverse cardiovascular outcome occurred in six patients (37.5%, four heart transplant and two ventricular assist device). In patients with an adverse cardiovascular outcome, median amino-terminal pro-B-type natriuretic peptide levels at day 7 were significantly higher (7,365 vs 1,196 pg/mL; p = 0.02) and the percent decline in amino-terminal pro-B-type natriuretic peptide was significantly smaller (28% vs 73%; p = 0.02) compared with those without an adverse cardiovascular outcome. Receiver operating curve analysis revealed that a less than 55% decline in amino-terminal pro-B-type natriuretic peptide levels at day 7 had a sensitivity and specificity of 83% and 90%, respectively, in predicting an adverse cardiovascular (area under the curve, 0.86; 95% CI, 0.68–1.0; p = 0.02). Conclusions: In conclusion, children with primary myocardial dysfunction and acute decompensated heart failure, a persistently elevated amino-terminal pro-B-type natriuretic peptide, and/or a lesser degree of decline in amino-terminal pro-B-type natriuretic peptide during the first week of presentation were strongly associated with adverse cardiovascular outcome. Serial amino-terminal pro-B-type natriuretic peptide monitoring may allow the early identification of children at risk for worse outcome.

Milrinone Pharmacokinetics in Critically Ill Children 179

Introduction:We investigated the pharmacokinetic characteristics of milrinone in critically ill children, a group in which pharmacokinetic data are limited. Methods:Fourteen children were enrolled and received a loading dose followed by a continuous infusion. Four to 9 timed blood samples were collected from each patient: prior to milrinone, at the end of the loading dose (C1), ≈24 hours later (C2), prior to (C3), and after stopping the infusion. [Milrinone] of extracted serum samples was measured by HPLC. The milrinone half-life (t1/2), steady state clearance (CLss), and volume of distribution (Vd) were calculated assuming 1st-order elimination with an open 1-compartment model. Results: The loading dose of milrinone (48.5±1.9 mcg/kg) resulted in C1 of 185 ±60 ng/ml and continuous infusion (0.5 mcg/kg/min) was associated with C2 of 83.4 ± 29.1 ng/ml. At discontinuation of the drug (in 5.3 ± 2.7 days) C3 was 61.4 ± 18 ng/ml (C2 v C3, p=ns). CLss was 8.2 ± 2.7 ml/kg/min, Vd was 0.66± 0.38 L/kg, and t1/2 was 58 ± 38 minutes. One patient developed multi-organ system failure (MOSF) and received an infusion of 0.25 mcg/kg/min: C3 was 241 ng/ml, [milrinone] was >200 ng/ml 2 hours after stopping the infusion, CLss was 1.0 ml/kg/min and t1/2 was markedly prolonged (> 8 hours). Excluding the patient with MOSF, age was not correlated with any kinetic parameter. However, C2 increased with increasing serum creatinine and bilirubin (p 100 ng/ml)[2]. However, [milrinone] declined during the infusion, suggesting a need to study increased infusion rates in children. Milrinone should be used with great care or avoided entirely in children with MOSF.

DOSE-RESPONSE RELATIONSHIP OF INHALED NITRIC OXIDE IN PEDIATRIC PATIENTS WITH ACUTE HYPOXEMIC RESPIRATORY FAILURE 221

DOSE-RESPONSE RELATIONSHIP OF INHALED NITRIC OXIDE IN PEDIATRIC PATIENTS WITH ACUTE HYPOXEMIC RESPIRATORY FAILURE 221

CHARACTERISTICS OF INVASIVE GROUP A BETA HEMOLYTIC STREPTOCOCCAL INFECTIONS IN CRITICALLY ILL CHILDREN. 274

Objective: To describe clinical and microbiological characteristics of a cluster of critically ill children with Group A Beta Hemolytic Streptococcal (GABS) infections. Design: Concurrent review. Setting: Pediatric intensive care unit of a university teaching hospital. Patients: Six children (mean age 3.4±2 yrs) with culture-proven GABS disease. Interventions: After routine hemodynamic and intensive care management, culture isolates of GABS were sent to the CDC, Atlanta GA, for surface protein identification and to the University of Minnesota Microbiology Department for exotoxin typing.Results: Five of six children were admitted in a 16 week period between March and July, 1994; the sixth in April, 1995. GABS was the causative organism for two cases of pneumonia with empyema and one case each of peritonitis, superinfection of thermal burn with inhalation injury, mastoiditis presenting as status epilepticus, and overwhelming septic shock. Bacteremia was documented in 4 of 6 patients (67%). Four patients (67%) fulfilled streptococcal shock syndrome(SSS) criteria.* The mean PRISM was 16±9 and the mortality rate was 17%. The acute respiratory distress syndrome (ARDS) occurred in four of five patients who required mechanical ventilation while the fifth was intubated for airway control. Pulmonary artery catheterization was performed in three patients. Two had elevated cardiac indices (CI)(5.9 and 4.73 I/min/m2) while the third, who died, had a depressed (2.33 I/m/m2) CI despite resuscitation. Systemic vascular resistances were decreased (788 dyneseccm2/cm5) or normal (1587) in the survivors and low normal(1438) in the patient who died. Four patients (67%) either had varicella or had recently been exposed to it. None had received ibuprofen. Evaluation of four GABS isolates revealed each produced exotoxin B, either alone, or in conjunction with exotoxin A. No M or T type predominance was identified.Conclusion: A cluster of invasive GABS cases occurred in a one year period. Hemodynamic patterns were similar to those seen in septic shock. Heightened suspicion for GABS disease should be maintained in ill children who have recently had, or been exposed to, varicella.