Suboptimal aminoglycoside dosing in critically ill patients.

Maximal aminoglycoside (AG) killing requires that the ratio of peak serum concentrations (Cmax) to the minimum inhibitory concentration (MIC) of the pathogen exceeds by > or =10. This has been shown to hasten resolution of infection in the general patient population. It was postulated that critically ill patients, likely to have larger intravascular volumes, are underdosed. The primary aim was to determine Cmax to MIC target attainment rate in medical intensive care unit (MICU) patients. A retrospective review of MICU patients who received at least 1 intravenous dose and serum concentration of either gentamicin or tobramycin was performed. A population pharmacokinetic model was developed, and MIC distributions for AG were used in determining the Cmax/MIC and in calculating the probability of attaining the pharmacodynamic (PD) target. One hundred two unique patients with 211 AG concentrations were analyzed to determine population pharmacokinetic parameters. Mean maximum clearance (CL) was 3.14L/h (95% confidence interval: 1.26-4.54 L/h), and mean volume of distribution (V) was 53 L (95% confidence interval: 38-66.8 L/h). Glomerular filtration rate and standardized body weight were identified as significant covariates for clearance in the final model. Standardized body weight also significantly affected V. There was only a 20% and 40% probability that patients receiving 7 mg/kg of gentamicin and tobramycin, respectively, will achieve PD target over the range of MIC distributions. Based on these data, the majority of critically ill patients would not be predicted to achieve the PD target under current dosing regimens. This may be a result of intensive care unit patients having a larger volume of distribution than reported in the literature. Future recommendations for treating gram-negative infections in the MICU population include using initial doses of 7 mg/kg of either gentamicin or tobramycin, measuring Cmax after the first dose, and determining MIC for the pathogen(s) with adjustment of subsequent doses to achieve the PD target.

Optimizing use of aminoglycosides in the critically ill.

In the era of increasing bacterial resistance and a lack of development of new antimicrobials for the treatment of gram-negative infections, aminoglycosides (AGs) are more commonly used in combination with other antimicrobials for the treatment of life-threatening infections in the intensive care unit (ICU). AGs display concentration-dependent killing activity; thus the rate and extent of bacterial killing increase with increasing peak (Cmax) drug concentrations. Optimizing AG dosing requires attainment of a pharmacodynamic target ratio (Cmax:minimal inhibitory concentration [MIC] > or = 10) upon first dose, which is associated with a more rapid rate of resolution of infection. Extended-interval AG dosing has been shown to attain this target in the general patient population while decreasing the risk of nephrotoxicity compared with multiple daily dosing. However, ICU patients have pharmacokinetic differences compared with patients who are less ill, including increased volume of distribution and variable clearance, which may make attainment of this target difficult. The need for extended-interval aminoglycoside dosing with Cmax monitoring and MIC determination of the pathogen may be needed to optimally treat serious infections in the critically ill.

Multicenter treatment and outcome evaluation of aspiration syndromes in critically ill patients.

BACKGROUND: Aspiration syndromes (pneumonia and pneumonitis) have significantly different processes. An evaluation of treatment and outcomes for these different syndromes has not been reported previously. OBJECTIVE: To characterize and assess antimicrobial prescribing patterns for aspiration syndromes in intensive care unit (ICU) patients and describe outcomes of those patients. METHODS: A retrospective, observational evaluation was conducted using a convenience sample of patients at 27 hospitals in North America; these patients were admitted to an adult ICU with a diagnosis of suspected/confirmed aspiration or had a suspected/confirmed aspiration while in the ICU. Hospital demographic, diagnosis, treatment, and clinical outcome data were collected. RESULTS: Over a 12 month period, 187 patients were observed. Aspiration syndromes included suspected aspiration (31%; n = 58), aspiration pneumonitis (12%; n = 23), aspiration pneumonia (55%; n = 103), and diagnosis not available (1.6%; n = 3). Antimicrobial management for the aspiration syndromes was as follows: suspected aspiration: 59% single agent, 38% multiple agents, and 3% no therapy; aspiration pneumonitis: 48% single agent, 39% multiple agents, and 13% no therapy; aspiration pneumonia: 48% single agent, 52% multiple agents, and 0% no therapy. Antimicrobial therapy was prescribed in patients with suspected (97%) and confirmed (100%) aspiration. Antibiotic therapy duration was significantly longer for aspiration pneumonia (9.1 +/- 7.5 days) than for aspiration pneumonitis (5.2 +/- 3.6 days; p = 0.013). Length of ICU stay was similar across patient groups. CONCLUSIONS: Antimicrobial agents are frequently prescribed to treat aspiration syndromes despite the lack of demonstrated efficacy for aspiration pneumonitis. Outcomes between aspiration syndromes were similar with the exception of duration of antibiotic treatment.

Atypical antipsychotics versus haloperidol for treatment of delirium in acutely ill patients.

Delirium is common in acutely ill patients and can result in substantial morbidity if left untreated. Atypical antipsychotics have been postulated to be safer and more effective than haloperidol for treatment of this condition. To evaluate the role of atypical antipsychotics versus haloperidol for treatment of delirium in hospitalized acutely ill adults, we searched MEDLINE (1977-September 2006) and International Pharmaceutical Abstracts (1997-September 2006) for English-language publications of clinical trials that compared atypical antipsychotics and haloperidol. Four comparative studies were identified: one double-blind, randomized study (risperidone vs haloperidol), one single-blind, randomized study (olanzapine vs haloperidol), and two retrospective studies (olanzapine vs haloperidol and quetiapine vs haloperidol). These studies demonstrated that atypical antipsychotics are as efficacious as haloperidol. In addition, they appear to be associated with a lower frequency of extrapyramidal effects, and thus are safer than haloperidol. However, these conclusions are based on a limited number of studies; larger comparative trials are needed to elucidate the role of atypical antipsychotics for treating delirium in this population.

Implementing an intravenous insulin infusion protocol in the intensive care unit.

PURPOSE: The implementation of three different insulin protocols in intensive care unit (ICU) settings in two community hospitals and one academic hospital is described. SUMMARY: Each institution possessed a commitment to improve the existing insulin protocols in order to achieve tighter glycemic control for ICU patients. Studies have shown that the maintenance of tight glycemic control provides improved patient outcomes. Obstacles to implementation of the insulin protocols at the institutions were increased staff workload, difficulties in interpreting algorithms, and lack of perceived benefit. In comparing details of the insulin protocols at the academic and community hospitals, it was found that differences were influenced by the type of institution. The differences among the institutions in the implementation of the protocols included the initial physician response to the protocol, the details of each protocol, nursing staff autonomy, and the involvement of the nursing staff in early protocol development. All three institutions had a dedicated pharmacist in the ICU who committed time toward insulin protocol implementation. For an increased likelihood of successful insulin protocol implementation, a full-time dedicated ICU pharmacist should be assigned to participate on multidisciplinary rounds, provide nursing support and education, and collect process measures to monitor and improve the protocol. CONCLUSION: The i.v. insulin infusion protocols developed and implemented in the ICUs at three institutions successfully achieved acceptance and compliance by physicians and nurses. The factors attributed to the success were multidisciplinary involvement, the continuous education of nursing staff, the vigilant involvement of a pharmacist, and flexibility in revising the protocol.

Pharmacy student response to patient-simulation mannequins to teach performance-based pharmacotherapeutics.

OBJECTIVE: To design and implement a simulated patient-case assessment using a mannequin for critical care pharmacotherapeutic education of doctor of pharmacy students and to evaluate student satisfaction with the simulation. DESIGN: During the second year of the doctor of pharmacy program, all students were required to complete Introduction to Critical Care. This course consisted of didactic education, written patient-case sessions, and an interactive patient simulation session. Information on the patient case was distributed to students after completing the didactic portion of the course. Patient information was programmed into a simulation mannequin, which demonstrated characteristics of a critically ill human. Students were surveyed post-simulation to determine the effectiveness of the learning experience. ASSESSMENT: The majority of students (88%) were extremely satisfied with the experience. The facilitator was considered to be extremely useful in 75% of responses. CONCLUSION: By simulating a patient case, the facilitator was able to control students' learning environment, adapt the simulation to the level of the students' performance, and debrief students immediately. Ultimately, by involving students in actual patient cases early in the pharmacy curriculum, this type of education could produce pharmacists with a high level of expertise and confidence.

Adverse-drug-event rates for high-cost and high-use drugs in the intensive care unit.

PURPOSE: The rates of adverse drug events (ADEs) associated with high-cost and high-use drugs in the intensive care unit (ICU) were studied. METHODS: This retrospective analysis was conducted from October 1997 through June 2001 in a 647-bed academic medical center with over 120 ICU beds. Adult patients with a documented ADE occurring in the ICU were included in the analysis. ADE information, including suspected medication, causality, preventability, and severity, was extracted from the institutional ADE database. Published definitions of ADEs and published scales for causality and severity assessments were used. High-cost medications were those in the top 50% of cumulative ICU medication costs, and high-use medications accounted for the upper 50% of all medications used in the ICU. Between-group comparisons of ADE rates, preventability, and severity associated with high-cost and high-use medications were conducted. RESULTS: Of the 17 medications that were considered high cost, 9 (53%) were associated with ADEs. Of the 15 medications that met the criteria for high-use drugs, 12 (80%) were associated with ADEs. The rates of ADEs associated with high-cost and high-use drugs did not significantly differ (43% versus 75%, respectively; p = 0.098). ADEs associated with high-cost and high-use medications were categorized as mild (15% versus 10%, respectively), moderate (52% versus 50%, respectively), and severe (33% versus 40%, respectively) (p > 0.05). CONCLUSION: The frequency, severity, and preventability of ADEs in the ICU were not associated with a drug's cost or frequency of use. Monitoring priorities of the critical care pharmacist should not be dictated by cost alone but should include frequency of use and the potential for causing an ADE.

Comparing intravenous amiodarone or lidocaine, or both, outcomes for inpatients with pulseless ventricular arrhythmias.

OBJECTIVE: To compare survival rates of patients with in-hospital cardiac arrest due to pulseless ventricular tachycardia/ventricular fibrillation treated with lidocaine, amiodarone, or amiodarone plus lidocaine. DESIGN: Multicenter retrospective medical record review. SETTING: Three academic medical centers in the United States. PATIENTS: Hospitalized adult patients who received amiodarone, lidocaine, or a combination for pulseless ventricular tachycardia/ventricular fibrillation between August 1, 2000, and July 31, 2002. MEASUREMENTS AND MAIN RESULTS: Data were collected according to the Utstein style. In-hospital proportion of patients living at 24 hrs and discharge were analyzed using chi-square analysis. Of the 605 patient medical records reviewed, 194 met criteria for inclusion (n=79 for lidocaine, n=74 for amiodarone, n=41 for combination). Available data showed no difference in proportion of patients alive 24 hrs post-cardiac arrest (p=.39). Cox regression analysis indicated a decreased likelihood of survival in patients with pulseless ventricular tachycardia/ventricular fibrillation as an initial rhythm as compared with those who presented with bradycardia followed by pulseless ventricular tachycardia/ventricular fibrillation and in those patients who received amiodarone as compared with lidocaine. However, only 14 patients (25%) in the amiodarone group received the recommended initial 300-mg intravenous bolus, and amiodarone was administered an average of 8 mins later in the code compared with lidocaine (p<.001). CONCLUSIONS: These results generate the hypothesis that inpatients with cardiac arrest may have different benefits from lidocaine and amiodarone than previously demonstrated. Inadequate dosing and later administration of amiodarone in the code were two confounding factors in this study. Prospective studies evaluating these agents are warranted.

Role of inhaled nitric oxide in adult heart or lung transplant recipients.

OBJECTIVE: To evaluate the role of inhaled nitric oxide (iNO) in adult heart or lung transplant recipients. DATA SOURCES: Pertinent literature was identified via a MEDLINE search (1966-July 2004). DATA SYNTHESIS: Pulmonary hypertension leading to right ventricular failure and ischemic reperfusion injury are complications following heart or lung transplant, respectively. A study of 16 heart transplant patients showed improvement in hemodynamic parameters and preservation of right ventricular function, but no improvement in mortality using iNO. Studies of lung transplant patients showed no benefit of iNO on mechanical ventilation duration, hospital length of stay, or mortality, but some studies indicate an improvement in hemodynamic parameters. CONCLUSIONS: iNO shows hemodynamic benefits in early postoperative heart transplant patients with preexisting pulmonary hypertension, and variable hemodynamic benefits in lung transplant recipients. Currently, morbidity and mortality data are not favorable for either indication; use of iNO is supportive and requires further study.