Lorazepam stability in parenteral solutions for continuous intravenous administration.

OBJECTIVE: To determine the stability of lorazepam over a 24-hour period when prepared in polyvinyl chloride (PVC) bags at initial concentrations of 0.08 and 0.5 mg/mL. DESIGN: Each concentration was studied at room (21 degrees C) and refrigerator (4 degrees C) temperatures in dextrose 5% (D5W) and NaCl 0.9% solutions. Duplicate test solution admixtures were prepared for each lorazepam concentration, diluent, and temperature. At 0, 1, 4, 8, and 24 hours, duplicate samples were obtained for visual inspection, pH determination, and concentration determination by stability-indicating, reverse-phase HPLC analysis. Compared with baseline, peaks for lorazepam degradation products were not found on any of the study chromatograms. RESULTS: In D5W and NaCl 0.9% solutions, lorazepam loss in excess of 10% by HPLC analysis occurred for concentrations of 0.08 and 0.5 mg/mL at 1 and 4 hours, respectively. CONCLUSIONS: These data suggest that significant loss of lorazepam occurs as the probable result of sorption to PVC bags when admixed in both D5W and NaCl 0.9% solutions at 21 and 4 degrees C.

A retrospective analysis of long-term use of nondepolarizing neuromuscular blocking agents in the intensive care unit, and guidelines for drug selection.

Nondepolarizing neuromuscular blocking agents (NNMBAs) are frequently administered to patients in the intensive care unit (ICU). We conducted a retrospective study of patients in intensive care who received infusions (> 48 hrs) of commonly used NNMBAs. The goals were to describe NNMBA use in our ICUs, determine patient characteristics, and assess the cost of the individual drugs. We found that atracurium was prescribed for 68% of study patients; 68% of the patients did not have renal, hepatic, or cardiovascular disease; dosages of NNMBAs varied; a statistically significant increase in dosage requirements over time occurred with atracurium; assessment of neuromuscular blockade was 100% subjective; and 41% and 17% of patients receiving atracurium and vecuronium, respectively, experienced prolonged neuromuscular weakness documented subjectively. As a result of this study, guidelines for agent selection were developed to facilitate cost effective use of NNMBA in our ICUs. Using these guidelines would potentially significantly decrease drug expenditures in this setting.

Response to pancuronium after loss of atracurium-induced neuromuscular blockade.

OBJECTIVE: To describe a previously unreported event in which a patient became refractory to atracurium-induced neuromuscular blockade, but subsequently was adequately paralyzed with a standard dosage of pancuronium. CASE SUMMARY: A previously healthy 17-year-old woman who sustained multiple trauma developed tolerance to an atracurium infusion she was receiving while undergoing mechanical ventilation. On day 3 of neuromuscular blockade, she became unresponsive to atracurium as evidenced by excessive physical movement, increased peak airway pressures, and overbreathing assist control ventilation. Repeat boluses and increases in the atracurium infusion rate to a maximum of 1.27 mg/kg/h failed to provide a desired clinical response. A bolus dose of pancuronium 0.15 mg/kg was administered and the constant infusion was then changed to pancuronium 0.078 mg/kg/h. Within minutes, decreased respirations, peak airway pressures, and agitation were noted. The pancuronium infusion rate was then tapered to 0.045 mg/kg/h over 72 hours and continued to maintain adequate neuromuscular blockade. DISCUSSION: Potential pharmacokinetic and pharmacodynamic causes of loss of neuromuscular blockade in this patient are postulated. Possible explanations for loss of neuromuscular blockade include increased degradation of atracurium and/or a change in acetylcholine receptor physiology. CONCLUSIONS: The development of resistance to a specific neuromuscular blocking agent in the intensive care setting does not necessarily imply cross-tolerance or resistance to alternative agents. Also, loss of respiratory control by one neuromuscular blocking agent may be overcome by changing agents.