Evaluation of sodium nitroprusside for controlled hypotension in children during surgery.

Purpose(1) To define the onset and offset of the blood-pressure-lowering effects of sodium nitroprusside (SNP) for use in developing instructions for dose titration in children undergoing a surgical or medical procedure, and (2) to assess the safety of SNP administration in pediatric patients requiring controlled reduction of blood pressure.MethodsWe conducted a randomized, double-blind, parallel-group, dose-ranging, effect-controlled, multicenter study of intravenous (IV) infusions of SNP in pediatric patients <17 years, who required controlled hypotension for at least 2 h while undergoing a surgical or medical procedure. A blinded SNP dose of 0.3, 1, 2, or 3 μg/kg/min was infused for 30 min, followed by open-label administration for at least 90 min. Both infusions were titrated to effect.ResultsThe final intent-to-treat group comprised 203 patients. Significant reductions in mean arterial pressure (MAP) from baseline were observed for all four doses at 20 and 25 min after the start of infusion (p ≤ 0.009 and p ≤ 0.010 for each time, respectively). Overall, 98.5% of the patients achieved the target MAP; 72.9% first achieved the target MAP during the blinded infusion. The mean infusion rate at target MAP was 1.07 μg/kg/min.ConclusionWe determined that 0.3 μg/kg/m is a reasonable starting dose for SNP in pediatric patients requiring controlled hypotension. The infusion rate can then be increased to achieve the desired reduction in blood pressure. On the basis of our results, we found an average infusion rate of 1 μg/kg/min might be appropriate. Of note, no cyanide toxicity was reported, and no measureable cyanide levels were detected in any blood samples obtained during the study. http://clinicaltrials.gov/show/NCT00135668

Evaluation of sodium nitroprusside for controlled hypotension in children during surgery.

Purpose(1) To define the onset and offset of the blood-pressure-lowering effects of sodium nitroprusside (SNP) for use in developing instructions for dose titration in children undergoing a surgical or medical procedure, and (2) to assess the safety of SNP administration in pediatric patients requiring controlled reduction of blood pressure.MethodsWe conducted a randomized, double-blind, parallel-group, dose-ranging, effect-controlled, multicenter study of intravenous (IV) infusions of SNP in pediatric patients <17 years, who required controlled hypotension for at least 2 h while undergoing a surgical or medical procedure. A blinded SNP dose of 0.3, 1, 2, or 3 μg/kg/min was infused for 30 min, followed by open-label administration for at least 90 min. Both infusions were titrated to effect.ResultsThe final intent-to-treat group comprised 203 patients. Significant reductions in mean arterial pressure (MAP) from baseline were observed for all four doses at 20 and 25 min after the start of infusion (p ≤ 0.009 and p ≤ 0.010 for each time, respectively). Overall, 98.5% of the patients achieved the target MAP; 72.9% first achieved the target MAP during the blinded infusion. The mean infusion rate at target MAP was 1.07 μg/kg/min.ConclusionWe determined that 0.3 μg/kg/m is a reasonable starting dose for SNP in pediatric patients requiring controlled hypotension. The infusion rate can then be increased to achieve the desired reduction in blood pressure. On the basis of our results, we found an average infusion rate of 1 μg/kg/min might be appropriate. Of note, no cyanide toxicity was reported, and no measureable cyanide levels were detected in any blood samples obtained during the study. http://clinicaltrials.gov/show/NCT00135668

Ondansetron to Reduce Neonatal Opioid Withdrawal Severity: A Randomized Clinical Trial

ObjectiveTo determine if treatment with a 5-HT3 antagonist (ondansetron) reduces need for opioid therapy in infants at risk for neonatal opioid withdrawal syndrome (NOWS). Study DesignA multicenter, randomized, placebo controlled, double blind clinical trial of ninety (90) infants. The intervention arms were intravenous ondansetron or placebo during labor followed by a daily dose of ondansetron or placebo in infants for five days. ResultsTwenty-two (49%) ondansetron-treated and 26 (63%) placebo-treated infants required pharmacologic treatment (p\u3e0.05). The Finnegan score was lower in the ondansetron-treated group (4.6 vs. 5.6, p=0.02). A non-significant trend was noted for the duration of hospitalization. There was no difference in need for phenobarbital or clonidine therapy, or total dose of morphine in the first 15 days of NOWS treatment. ConclusionsOndansetron treatment reduced the severity of NOWS symptoms; and there was an indication that it could reduce the length of stay

A Hemodynamic Model to Guide Blood Pressure Control During Deliberate Hypotension with Sodium Nitroprusside in Children

Sodium nitroprusside (SNP) has been widely used to control blood pressure in infants and children. The goals of this analysis were to develop models that describe the hemodynamic response to SNP dosing in pediatric patients; examine sources of variation in dose-response, defining age and size dependencies; and determine vulnerable populations or patient subtypes that may elicit dosing modifications. A multi-center, randomized, double-blinded, parallel-group, dose-ranging, effect-controlled study, followed by an open-label dose titration of an intravenous infusion of SNP was undertaken in 203 pediatric subjects, who required deliberate hypotension or controlled normotension during anesthesia. A total of 3,464 MAP measurements collected from 202 patients during the study’s blinded phase, including baseline measurements up to 6 min prior to the blinded were available for analysis. A population K-PD model was developed with a one-compartment model assumed for SNP. Size differences in CL and V of the effect compartment were described using theory-based allometry. An inhibitory sigmoidal Emax model was used to describe the effect of SNP. A power function of age was used to describe age-related differences in baseline MAP. A mixture model of two groups with low and high EC50 was used to explain variability in MAP response. Change in MAP was characterized by a linear disease progression slope during the blinded phase. In the final population model, CL and V increased with weight, and baseline MAP increased with age. The effect compartment half-life of SNP was 13.4 min. The infusion rate producing 50% of Emax (ER50) at steady state for high EC50, was 0.34 µg/kg/min and for low EC50 0.103 µg/kg/min. The K-PD model well describes initial dosing of SNP under controlled circumstances; model-based dosing guidance agrees with current practice. An initial titration strategy supported via algorithm-based feedback should improve maintenance of target MAP