Daniel Stromberg

Myocardial inflammatory activation in children with congenital heart disease

Objective In several cardiac-related diseases, there is a strong association between systemic endotoxemia, myocardial cytokine production, and cardiac failure. Because pre- and postoperative endotoxemia recently was reported in children with congenital heart disease, we sought direct evidence of myocardial inflammatory activation in a cohort of children undergoing congenital heart surgery on cardiopulmonary bypass. Inflammatory activation was prospectively defined as the presence of nuclear factor-&kgr;B nuclear translocation in myocardial tissue samples. Design Prospective observational study. Setting Tertiary care pediatric intensive care unit. Patients Fifteen children with congenital heart disease undergoing operative repair on cardiopulmonary bypass. Interventions All patients underwent operative repair of congenital heart disease on cardiopulmonary bypass and had plasma samples obtained for endotoxin and tumor necrosis factor-&agr;, both pre- and postoperatively. Myocardial tissue samples were obtained intraoperatively, both before and during cardiopulmonary bypass. Measurements and Main Results Elevated plasma endotoxin concentrations were documented in all 15 patients during the study period. In 12 patients, plasma endotoxin was elevated before cardiopulmonary bypass. The median preoperative tumor necrosis factor-&agr; concentration was 16.4 pg/mL, which is higher than concentrations reported in adults with New York Heart Association class III congestive heart failure. Examination of myocardial tissue samples revealed nuclear factor-&kgr;B nuclear translocation (predominantly p50/p65 heterodimers) in nine of 15 patients (60%). Four of these nine patients had nuclear factor-&kgr;B nuclear translocation before initiation of cardiopulmonary bypass, with p50/p50 homodimers present in two of the four. Conclusions These data provide the first evidence of nuclear factor-&kgr;B activation in children with congenital heart disease and the first evidence of myocardial nuclear factor-&kgr;B translocation in human hearts before explant for transplantation. Furthermore, these data suggest that, similar to adults with advanced congestive heart failure, the myocardial inflammatory cascade may contribute to the pathophysiology of congenital heart disease in infants and children.

Effect of Low-Dose Naloxone Infusion on Fentanyl Requirements in Critically Ill Children

OBJECTIVE. Sedating critically ill patients often involves prolonged opioid infusions causing opioid tolerance. Naloxone has been hypothesized to limit opioid tolerance by decreasing adenylate cyclase/cyclic adenosine monophosphate activation. The study purpose was to investigate the effect of low-dose naloxone on the maximum cumulative daily fentanyl dose in critically ill children. METHODS. We conducted a double-blinded, randomized, placebo-control trial from December 2002 through July 2004 in a university PICU. We enrolled 82 children age 1 day to 18 years requiring mechanical ventilation and fentanyl infusions anticipated to last for >4 days were eligible for enrollment. Those receiving additional oral analgesia or sedation, having a history of drug dependence or withdrawal, or having significant neurologic, renal, or hepatic disease were excluded. In addition to fentanyl infusions, patients received low-dose naloxone or placebo infusions. Medications were adjusted using the Modified Motor Activity Assessment Scale. Withdrawal was monitored using the Modified Narcotic Withdrawal Scale. Intervention was a low-dose naloxone infusion (0.25 μg/kg per hour) and the main outcome variable was the maximum cumulative daily fentanyl dose (micrograms per kilogram per day). RESULTS. There was no difference in the maximum cumulative daily fentanyl dose between patients treated with naloxone (N = 37) or those receiving placebo (N = 35). Adjustment for the starting fentanyl dose also failed to reveal group differences. Total fentanyl dose received throughout the study in the naloxone group (360 μg/kg) versus placebo (223 μg/kg) was not statistically different. Placebo patients trended toward fewer rescue midazolam boluses (10.7 vs 17.8), lower total midazolam dose (11.6 mg/kg vs 23.9 mg/kg), and fewer rescue fentanyl boluses (18.5 vs 23.9). CONCLUSIONS. We conclude that administration of low-dose naloxone (0.25 μg/kg per hour) does not decrease fentanyl requirements in critically ill, mechanically ventilated children.

Usefulness of external counterpulsation early postoperatively after the Fontan procedure in children

temic venous return, and reduces ventricular afterload. 1‐3 We hypothesized that EC could benefit patients who underwent the Fontan procedure by improving cardiac output in the early postoperative period. EC had not been studied in the postoperative setting, and had never previously performed in the pediatric population. Therefore, this investigation sought to provide preliminary evidence of EC safety and short-term efficacy in children after Fontan surgery. ••• We performed a prospective, within-patient, controlled investigation of EC in children who underwent the Fontan procedure (fenestrated and nonfenestrated) at Children’ s Medical Center, Dallas, from May 1999 to June 2001. Children were considered for participation in the study if they were consecutive pediatric patients for whom parental consent was obtained, if there was an EC machine available, and if EC cuff sizes were deemed appropriate (pediatric-sized cuff straps able to be tightened over a sheepskin barrier to prevent excessive movement and skin irritation during EC). Patients were excluded from study for the following reasons: significant intraoperative surgical complications that may have compromised postoperative neurologic status (defined as 10 minutes of hypotension off bypass with blood pressure less than the fifth percentile for age), extubation before or immediately upon arrival to the cardiac intensive care unit, presence of a cardiac arrhythmia or paced heart rhythm, invasive line(s) in the femoral or lower extremities, peripheral vascular disease, musculoskeletal anomaly involving the lower extremities, significant and prolonged postoperative hemorrhage (3 ml/kg/ hour persisting for 10 hours after arrival to the cardiac intensive care unit), or aortic insuf ficiency. After admission to the cardiac intensive care unit, each patient was assessed for clinical stability. Blood products and/or volume (5% albumin) were administered and inotropes were adjusted at the discretion of the attending physician based on hemodynamic status, chest tube drainage, hemoglobin level, and degree of anticoagulation. Intravenous fluid was administered before the investigation if systemic perfusion was determined to be clinically poor, or if systolic blood pressure decreased below the fifth percentile for age at any time. The study protocol was initiated while patients were sedated and anesthetized with midazolam and fentanyl, before extubation, and after mediastinal blood loss was controlled (3 ml/kg/hour). Inotropes and vasoactive medications were unchanged during the period of investigation. The study protocol was divided into 3 10-minute periods. During the first period, baseline parameters were measured before initiation of EC. This was immediately followed by a 10-minute EC period, and directly thereafter, a postintervention period. The hemodynamic parameters obtained during all 3 periods included cardiac index (CI) by ascending aortic pulse Doppler echocardiography (averaged over 8 cardiac cycles), 4 vital signs (heart rate, blood pressure), and central venous pressure (CVP). Each parameter was measured every minute during the 3 study intervals, except ascending aortic Doppler flow, which was evaluated every 2 minutes. Echocardiographic determinations of CI were made off-line by a single interpreter who was blinded to the period of testing. Blinded interpretation was feasible because EC does not alter ascending aortic Doppler flow patterns.5 Chest tube output and oxygen saturation were recorded throughout the investigation. EC was performed using the Cardiomedics Cardi

Waiver of Prospective Consent for Pediatric Resuscitation Research

To the Editor .— We read with interest the recent Pediatrics article “Exception From Informed Consent for Pediatric Resuscitation Research: Community Consultation for a Trial of Brain Cooling After In-Hospital Cardiac Arrest.”1 The article described parental and hospital staff opinions of informed consent relevant to study of induced hypothermia after pediatric cardiac arrest. Focus groups identified attempts to obtain informed consent at the time of hospital or intensive care unit (ICU) admission as particularly problematic. Difficulties with this a priori approach included (1) lack of parental receptivity to research/consent conversations during the stress of admission, (2) inattention to the consent document and its contents when parents believe the likelihood of study applicability to their child is low, (3) anxiety generation in a large number of parents forced to contemplate the cardiac arrest of their child, and (4) extraordinary labor demands and logistic difficulties associated with obtaining prospective consent from all patients admitted to either the hospital or ICU.1 We recently began a study of pediatric interposed abdominal compression cardiopulmonary resuscitation (CPR). Based on existing adult and pediatric data, the study poses minimal risk to children and may be beneficial when results of standard …