Prospective documentation of sedative, analgesic, and neuromuscular blocking agent use in infants and children in the intensive care unit: A multicenter perspective.

OBJECTIVE: To describe the use of neuromuscular blocking agents (NMBA) in critically ill children. DESIGN: Prospective cohort study. SETTING: Two pediatric intensive care units (ICUs). PATIENTS: All children who received NMBA in the ICUs during the study year. INTERVENTIONS: None Measurements: Data on use of NMBA agents and concurrent use of narcotic and sedative agents were collected. Demographic and outcome information was also obtained. MAIN RESULTS: NMBAs were used for either short-term (<6 hrs) or long-term neuromuscular blockade in 6%-9% of patient ICU days and for long-term blockade in 14%-16% of ventilatory support days. The overall mortality rate among ICU patients who received NMBA was 18%. Choice of agent varied between ICUs; however, succinyl choline was used in only 1% of cases for short-term neuromuscular blockade. The most frequent indication for long-term NMBA use was facilitation of mechanical ventilatory support (49%). Among these children, 46% received high frequency oscillatory ventilation. Long-term neuromuscular blockade was most frequently monitored by clinical examination rather than peripheral nerve stimulation. Paralysis for >6 hrs after discontinuation of NMBA was significantly more common when the agent was administered as an infusion instead of as bolus doses. Myopathy after long-term use of NMBA was seen in only 1 patient (0.4%). Doses (mg/kg) of NMBA did not significantly vary by patient age, but they did increase over time. CONCLUSIONS: Use of NMBA is more common in critically ill children than in reported studies of critically ill adults. Use of NMBA in critically ill children is associated with high severity of illness and mortality rates. Choice of NMBA and method of administration varies among providers. Concurrent use of narcotic and sedative agents with NMBA is frequent, but medication choice also varies among medical providers.

Pandemic flu and the sudden demand for ECMO resources: a mature trauma program can provide surge capacity in acute critical care crises.

BACKGROUND: Patients with severe H1N1 pneumonia created a sudden demand for extracorporeal membrane oxygenation (ECMO) capacity. In a single referral center, the established procedures, protocols, and staff of the Level I trauma service were adapted to help manage this nontrauma critical care crisis. METHODS: When airway pressure release ventilation and high-frequency oscillator ventilation failed, we used standard ECMO circuits and the VDR-4 critical care ventilator. We cannulated patients percutaneously in the intensive care unit and transported them on ECMO. Trauma service resources included a mobile surgical transport team, direct to OR resuscitations, massive transfusion protocols, trauma performance improvement processes, trauma resuscitation nurses, in-house attending doctors, and experienced staff familiar with protocol-driven care. RESULTS: During an 84-day period, 15 patients with severe H1N1 pneumonia were treated with ECMO. All patients were referred; 10 were transported on ECMO. Patients were aged 34.4 ± 4.1 years (6-58 years); 47% were male, and they had been ventilated 3.5 ± 0.8 days. Pre-ECMO PaO2/FIO2 ratios were 62.3 ± 6.1; ECMO duration was 9.4 ± 1.3 days for survivors; and post-ECMO PaO2/FIO2 ratio was 295.0 ± 35.1. Recovery occurred in 67% and 60% survived to discharge. No patient died of lung failure. Surviving patients were discharged at their neurologic baseline. CONCLUSION: H1N1 created a severe public health challenge for referral centers with ECMO capability. The resources of our trauma service were adapted to this nontrauma critical care crisis without disruption of other hospital services. These H1N1 patients treated with ECMO had a 67% recovery rate and a 60% survival rate. All survivors were discharged to home. LEVEL OF EVIDENCE: Therapeutic/epidemiologic study, level V.

The role of trace elements in homeopathic preparations and the influence of container material, storage duration, and potentisation.

OBJECTIVE: To investigate trace elements in liquid homeopathic preparations and the influence of container material, storage duration, and potentisation. MATERIALS AND METHODS: Using inductively coupled plasma-mass spectroscopy (ICP-MS), we investigated (a) aqua bidestillata (ABD) stored for 12 h in either brown glass or high density polyethylene (HDPE) bottles; (b) ABD stored for 2 h in HDPE, the same additionally filled in brown glass bottle, and ABD potentised in brown glass up to C30; (c) -- at 3 different sample ages and with statistical analysis -- ABD C30 (brown glass), AgNO3 C30 (brown glass), and controls (unsuccussed, brown glass and HDPE). RESULTS: Contamination of the initial ABD increased and element concentrations changed far more when stored in brown glass bottles than in HDPE. Effects were strongest during initial storage time and during the first potentisation step from mother tincture to C1; subsequent potentising steps produced no relevant changes. Potencies of AgNO3 and potencies of water contained similar contamination. CONCLUSIONS: Potentising accelerates material exchange between container and solvent, mostly during succussion. Research on potentised preparations should use potentised controls with equal preparation and storage time. If physical and biological effects of potencies exist, contaminants might be one factor for their generation.

Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis.

OBJECTIVE: In a phase 3 trial, recombinant human activated protein C (drotrecogin alfa [activated]) significantly reduced mortality in adult patients with severe sepsis. We have now performed a preliminary analysis of the safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in pediatric patients with severe sepsis. DESIGN AND SETTING: Open-label, nonrandomized, sequential, 2-part study conducted in 11 medical centers in the United States and United Kingdom. PATIENTS: Eighty-three pediatric patients with severe sepsis aged term newborn (>or=38 weeks' gestation) to <18 years old. INTERVENTION: In part 1, drotrecogin alfa (activated) was administered as escalating doses of 6, 12, 24, and 36 micro g/kg per hour for 6 hours for each patient (n = 21). In part 2, drotrecogin alfa (activated) was infused at a rate of 24 micro g/kg per hour for 96 hours in 62 patients. MAIN OUTCOME MEASURES: Plasma clearance, plasma concentration, D-dimer, protein C, and antithrombin levels were measured, and adverse events were monitored. RESULTS: The trial enrolled 83 pediatric patients with severe sepsis, aged term newborn (>or=38 weeks' gestation) to <18 years. In part 1, a dose of 24 micro g/kg per hour produced steady-state plasma concentrations of activated protein C similar to those attained in equivalently dosed adult severe sepsis patients. For all pediatric patients dosed at 24 micro g/kg per hour, the median weight-normalized clearance was 0.45 L/hour/kg and the median steady-state concentration was 51.3 ng/mL. The mean plasma half-life was 30 minutes. Weight-normalized clearance in pediatric and adult patients did not differ significantly with age or weight. D-dimer levels decreased 26% from baseline to end of infusion. Baseline levels of protein C and antithrombin increased 79% and 24%, respectively, over the 96-hour treatment period in part 2. The incidence of serious bleeding during infusion and during the entire study period was 2.4% and 4.8%, respectively. CONCLUSIONS: Pediatric patients with severe sepsis manifest sepsis-induced coagulopathy including protein C deficiency comparable to that seen in adults with severe sepsis. The pharmacokinetics, pharmacodynamic effects, and safety profile of drotrecogin alfa (activated) in pediatric patients are similar to those previously published for adult patients. A large, phase 3, randomized, placebo-controlled study is ongoing to confirm these results and formally assess the safety and efficacy of drotrecogin alfa (activated) in children.