P. Shane Winstead

Rhabdomyolysis during therapy with daptomycin.

The use of daptomycin has been associated with an elevation in creatine phosphokinase level, with a reported incidence of 2.8% in phase III clinical trials. Published case reports have documented the presence of myopathy in patients who received daptomycin; however, there have been no previously reported cases of rhabdomyolysis in animals or humans to date. We describe a case of rhabdomyolysis during therapy with daptomycin.

Recombinant human erythropoietin therapy in critically ill Jehovah's Witnesses.

Blood transfusions and blood products are often given as a life‐saving measure in patients with critical illness. However, some patients, such as Jehovahs Witnesses, may refuse their administration due to religious beliefs. Jehovahs Witnesses accept most available medical treatments, but not blood transfusions or blood products due to their religions interpretation of several passages from the Bible. Since recombinant human erythropoietin (rHuEPO) became available, several cases have been reported in which rHuEPO was successfully administered to critically ill Jehovahs Witnesses. Administration of rHuEPO in combination with other blood conservation techniques has been shown to increase hemoglobin levels and survival in patients who experienced trauma, burns, general surgery, or gastrointestinal hemorrhage. We performed a literature search of the MEDLINE and International Pharmaceutical Abstracts databases of rHuEPO therapy in the Jehovahs Witness population. Fourteen cases were identified in which rHuEPO was administered to Jehovahs Witnesses who required the drug for critical care resuscitation as an alternative to blood products. In each clinical situation, rHuEPO enhanced erythropoiesis; however, time to the start of treatment, dosages, route of administration, and treatment duration varied widely. Supplementation with adjunctive agents, such as iron, folic acid, and vitamin B12, was also beneficial. Use of rHuEPO in Jehovahs Witnesses may provide an alternative to blood transfusions or blood products. Other alternatives, such as hemoglobin‐based oxygen carriers and perfluorocarbons, are also being explored.

Pharmacokinetic Alterations in Obesity

Although some medications have established dosing adjustments for obesity (Table 2), it remains unknown for the majority of medications if dosing adjustment is warranted. It is important to remember dosage adjustments may not be as simple as doubling an antibiotic dose because a patient is morbidly obese. Individualizing drug dosing is imperative in the obese, postoperative patient to ensure they simultaneously have therapeutic serum concentrations without drug toxicity. Much of what has been learned from studies in obese patients is that the pharmacokinetic alterations of medications are variable. Broad application of dosing guidelines even among medications within the same therapeutic class is likely not appropriate. An increased emphasis in researching the effects of obesity on the fate of medications is of paramount importance as the obese population grows. Practitioners should use caution and be vigilant in monitoring pharmacotherapy in obese individuals.

Prolonged cardiac repolarization after tacrolimus and haloperidol administration in the critically ill patient

A 42‐year‐old woman who underwent single lung transplantation who received tacrolimus and a 58‐year‐old woman with pneumonia and multiple comorbidities who received haloperidol both experienced drug‐induced prolongation of cardiac repolarization. The second woman also developed torsade de pointes. Critically ill patients are particularly susceptible to developing torsade de pointes due to various comorbidities, electrolyte disturbances, and receipt of numerous drugs. These two case reports illustrate the increased risk for drug‐induced cardiotoxicity in the critically ill patient. They also indicate the need for current knowledge derived from basic research and retrospective case reports on drug‐induced torsade de pointes to be integrated into the existing body of knowledge. Guidelines can then be developed to help prospectively reduce the frequency of adverse effects in intensive care patients. Research is necessary regarding identification of high‐risk patients before drugs are administered, and clarification of the proper role of therapeutic QT monitoring in clinical practice.

Effects of a Pharmacist-to-Dose Computerized Request on Promptness of Antimicrobial Therapy

OBJECTIVES To examine the effects of computerized requests for pharmacist-to-dose (PTD), an advanced clinical decision support tool for dosing guidance, on antimicrobial therapy with vancomycin and aminoglycosides, describe PTD request utilization, and identify factors that may prolong this process. DESIGN A retrospective review was conducted of patients hospitalized from Jan 2004 to Jun 2006 with suspected pneumonia who received vancomycin, tobramycin, or gentamicin via PTD (study) or routine provider order entry (control). MEASUREMENTS The primary endpoint was time to pharmacist completion of PTD request. Secondary data points included medication turn-around times for first doses of vancomycin or aminoglycosides and for first doses of any antibiotic, dose adjustment for renal dysfunction, medication errors, and time of order entry. Multivariate analysis was conducted to identify predictors of total time to pharmacist verification and time to administration of first doses of vancomycin or aminoglycosides. RESULTS Median time for pharmacist completion of PTD requests was 29 minutes. Delays were noted in the study group (n = 49) by comparison with the control group (n = 48) for median time to first dose of vancomycin or aminoglycoside (185 vs. 138 min, p = 0.45) and for any antibiotic (134 vs. 118 min, p = 0.42), respectively. Fewer medication errors were reported in the study group (5 vs. 18 errors, p = 0.002). In a multivariate model, PTD was not significantly predictive of time to pharmacy verification or medication turn-around time. CONCLUSIONS Pharmacists completed pharmacist-to-dose consultations for dosing guidance of vancomycin and aminoglycosides within a median of 30 minutes. Implementation of a computerized request for clinical pharmacists to provide medication-related clinical decision support increased medication turn-around time of vancomycin and aminoglycosides and reduced medication errors. Consultation of clinical pharmacists by computerized request for initial antibiotic dosing of medications with narrow therapeutic windows is an option for medication-related clinical decision support but providers should be aware that consultation may delay medication turn-around time.

Vancomycin Clearance in High-Volume Venovenous Hemofiltration

OBJECTIVE To report the pharmacokinetic and pharmacodynamic properties of vancomycin in 4 patients undergoing high-volume continuous venovenous hemofiltration (CVVH). CASE SUMMARY Data from 4 patients prescribed high-volume CVVH for acute renal failure treated with vancomycin were analyzed. Vancomycin plasma concentrations were measured 4 and 24 hours after the end of a 1-hour vancomycin infusion. The mean therapy fluid rate on initiation of vancomycin was 56.2 mL/kg/h (range 48.0–65.5). The mean loading dose of vancomycin was 18.3 mg/kg (range 14.7–19.7). Median vancomycin concentration 4 hours after the dose was 18.1 mg/L (range 13.1–30.0). At 24 hours after the dose, only 1 patient had a detectable vancomycin concentration (5.2 mg/L). DISCUSSION There was a large variability in the clearance of vancomycin in this patient population. Current strategies for dosing vancomycin may lead to subtherapeutic trough concentrations. Vancomycin dosing in this patient population should be based on a detailed assessment of the CVVH prescription, vancomycin concentrations, and clinical needs and response. CONCLUSIONS An initial vancomycin dose of 20–25 mg/kg with frequent monitoring and adjustment is recommended for patients receiving high-volume CVVH.

Alcohol Withdrawal Syndrome

Alcohol withdrawal syndrome is a significant problem that can complicate underlying disease states and lead to serious clinical consequences. The recognition of the early signs and symptoms of this syndrome, as well as the identification of those at highest risk for developing it, is crucial for effective prevention and management. Multiple pharmacotherapy options exist, and therapy should be guided on the basis of patient-specific factors and clinical presentation. The optimal care of these patients is dependent on a multidisciplinary approach to provide appropriate evaluation, treatment, and follow-up.

Evaluation of Continuation of Stress Ulcer Prophylaxis at Hospital Discharge

Purpose Stress-related mucosal disease (SRMD) can adversely affect patient morbidity and mortality. The use of stress ulcer prophylaxis (SUP) in patients with no risk factors for clinically important bleeding, however, is contributing to health care-related adverse events, drug interactions, and costs. The objective was to determine the percentage of hospitalized patients who receive SUP without an approved indication and to evaluate the financial impact of inappropriate prescribing as well as the risk for significant drug-drug interactions. Methods A retrospective chart review was performed of hospitalized adult cardiology, family medicine, and internal medicine patients between July 1, 2006 and June 30, 2007. Prescribing of acid suppressive therapy (AST) during hospital admission and indications for SUP were evaluated. Concomitant medications, cost of therapy, and discharge medications were assessed as secondary outcomes. Results Of the 4,603 patients admitted during the study period, 418 were randomly selected for study inclusion. Approximately 53% (221/418) of the selected patients received SUP during hospital admission, 93% (206/221) of whom had no indication for prophylaxis. Of those who continued AST at discharge (14%; 31/221), 84% (26/31) had no approved indication. Overuse of SUP resulted in 77 potential drug-drug interactions and an estimated 30-day outpatient cost of

Pharmacy resident participation with a 24-hour multidisciplinary stroke response team

37,950 for patients receiving these medications at discharge. Conclusion SUP is frequently prescribed to non–critically ill patients when the risk of SRMD is low. Use of SUP for patients who do not meet evidence-based criteria appears to contribute to increased health care expenditures, potential adverse events, and drug interactions.

Current Controversies in Critical Illness-related Corticosteroid Insufficiency and Glucocorticoid Supplementation

Stroke is an increasingly common reason for emergency department (ED) visits in the United States, affecting over 700,000 patients per year.[1][1] It is estimated that 80% of all strokes are ischemic strokes. However, despite the frequency of strokes and their substantial morbidity and mortality,