Lori L. Hoey

QTc-interval prolongation associated with slow intravenous erythromycin lactobionate infusions in critically ill patients: a prospective evaluation and review of the literature.

Intravenous erythromycin has recently been associated with significant QTc interval prolongation, torsades de pointes, and sudden cardiac death. The prolonged the QTc interval attributed to erythromycin typically is associated with rapid infusion rates in excess of 10 mg/minute. We prospectively assessed the relationship between QTc interval prolongation and erythromycin administration by slow intravenous infusion (mean rate 8.9 ± 3.5 mg/minute, range 3.9–16.7 mg/minute). Electrocardiographic (ECG) rhythm strips were prospectively obtained in 44 critically ill patients receiving intravenous antibiotics (22 received erythromycin and 22 ceftazidime, cefuroxime, cefotaxime, ceftriaxone, or ampicillin‐sulbactam as controls). The ECG recordings were obtained immediately before and within 15 minutes after drug infusions. Only the first available set of ECG strips were evaluated. Two controls had evidence of hepatic dysfunction; no patients receiving erythromycin did. The QTc interval was calculated using Bazetts formula by two blinded investigators. For controls, mean ± 1 SD (range) QTc intervals were 423 ± 96 (300–550) msec at baseline and 419 ± 96 (280–610) msec after infusion (p=0.712). In contrast, in the erythromycin group, the interval was significantly prolonged from 524 ± 105 (360–810) msec at baseline to 555 ± 134 (400–980) msec after infusion (p=0.034). No patients experienced a dysrhythmia as a consequence of erythromycin infusion. Despite slow rates of infusion, QTc interval prolongation was significant. The clinical importance of this finding remains to be determined.

Wide variation in single, daily-dose aminoglycoside pharmacokinetics in patients with burn injuries.

Five to seven mg/kg single, daily-dose aminoglycoside regimens have been recently advocated as effective alternatives to traditional aminoglycoside regimens. The rationale for single, daily-dose aminoglycoside therapy is to produce an optimal ratio between aminoglycoside peak concentrations (Cmax) and pathogen minimal inhibitory concentration to maximize bacterial killing and to produce an aminoglycoside-free period during the 24-hour dosing interval. Single, daily-dose aminoglycoside therapy has not been recommended to date for use in the population of patients with burn injuries. The purpose of this study was to determine the magnitude and variability of aminoglycoside Cmax and the duration of the aminoglycoside-free period after simulated single, daily-dose regimens in patients with burn injuries. Fifty-two patients receiving gentamicin or tobramycin in the burn unit were studied retrospectively to determine the individualized pharmacokinetic parameters and the simulated Cmax and 24-hour after the dose trough minimum concentrations for 5 and 7 mg/kg single, daily-dose aminoglycoside regimens. Patients were only included in the final analysis if they had been treated for burn wound infections and exhibited a calculated creatinine clearance exceeding 60 ml/min (N = 40). Mean [percentage coefficient of variation] Cmax/minimum concentrations were 15.4[30.5]/0.03[200.0] and 21.6[30.6]/0.04[200.0] mg/L for 5 and 7 mg/kg daily doses, respectively. The mean coefficient of variation time to reach an extrapolated concentration of 0.1 mg/L was 15.9[30.8] hours and 17.0[30.6] hours for the 5 and 7 mg/kg daily doses, respectively. Substantial variability in aminoglycoside Cmax and duration of the aminoglycoside-free period was observed. These data suggest that many patients with burn injuries are not candidates for single, daily-dose aminoglycoside therapy because of restrictive creatinine clearance criteria and pronounced variability in length of the aminoglycoside-free interval. If single, daily-dose aminoglycoside therapy is to be used in this patient population, therapeutic drug monitoring is recommended to screen for appropriate candidates and to optimize Cmax and minimal inhibitory concentration ratios and duration of the aminoglycoside-free interval.

Prolonged Neuromuscular Blockade in Two Critically Ill Patients Treated With Atracurium

Recent literature suggests that the risk of prolonged neuromuscular blockade associated with atracurium compared with other nondepolarizing neuromuscular blocking agents may be minimal. Two patients experienced prolonged weakness associated with the administration of atracurium. Both received atracurium 0.5–0.7 mg/kg/hour in combination with methylprednisolone 500–600 mg/day. Electromyographic results and creatine kinase levels were suggestive of muscular weakness in both patients. Despite high‐dose corticosteroid therapy, the electromyographic evidence supporting prolonged weakness did not suggest typical corticosteroid myopathy. Although some clinicians advocate routine administration of atracurium in critically ill patients due to the relative lack of reports of prolonged weakness, this may be premature. Although there are fewer reports of atracurium‐associated prolonged weakness compared with pancuronium and vecuronium, the patients we describe suggest that it may occur.

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°C) and refrigerator (4°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°C.

Atracurium Resistance in a Critically Ill Patient

A previously healthy 25‐year‐old man with metastatic testicular teratocarcinoma became resistant to atracurium‐induced neuromuscular blockade as evidenced by train‐of‐four (TOF) monitoring combined with clinical assessment. Subsequently he had an adequate response with a standard dosage of pancuronium. During the first 10 days of neuromuscular blockade, the atracurium requirements escalated from 0.31 to 1.7 mg/kg/hour, guided by TOF monitoring, movement, and spontaneous respirations. The infusion was discontinued but later reinstituted. Despite a total atracurium loading dose of 1.4 mg/kg followed by an infusion rate titrated to 1.7 mg/kg/hour, inadequate paralysis persisted. Atracurium was terminated and an intravenous infusion of pancuronium 0.10 mg/kg/hour was started. Over the next 3 days the pancuronium infusion was titrated down to a range of 0.04‐0.06 mg/kg/hour, followed by a maintenance infusion of 0.01‐0.05 mg/kg/hour for 5 days. A pharmacokinetic alteration, such as increased metabolism or elimination, may have caused the atracurium resistance.

A retrospective review and assessment of benzodiazepines in the treatment of alcohol withdrawal in hospitalized patients

Little information has been published concerning differences among the benzodiazepines in treating hospitalized patients with severe symptoms of alcohol withdrawal. We attempted to determine the length and type of hospital stay, and the pattern and appropriateness of administration, dosage requirements, and costs associated with benzodiazepines in patients undergoing alcohol withdrawal. A 1‐year retrospective analysis was performed for 57 hospitalized patients. Appropriate therapy was defined as lorazepam for patients 60 years and older or those with hepatic dysfunction, and chlordiazepoxide or diazepam for all other patients. Drug costs were calculated based on acquisition costs. The mean number of days of benzodiazepine treatment and length of stay in the intensive care unit (ICU) were 6.2 days (range 1–30 days) and 3.9 days (range 0–12 days), respectively. Fifty‐six patients were admitted to the ICU for management or for monitoring continuous‐infusion lorazepam; one patient received chlordiazepoxide on a general ward. Total mean lorazepam infusion required per patient was 324 mg (range 2–5956 mg). The total benzodiazepine acquisition cost was

Resistance to nondepolarizing neuromuscular blocking agents

56,489 (mean

Inconsistency With Train‐of‐Four Monitoring in a Critically Ill Paralyzed Patient

1009, range

Train‐of‐Four: To Use or Not to Use

0.06–7157/patient). The total costs of benzodiazepine acquisition and ICU charge were

The impact of practice guidelines on prescribing patterns of nondepolarizing neuromuscular blocking agents

404,346 (mean