Rhonda S. Rea

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 ≥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.

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.

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. LEARNING OBJECTIVESOn completion of this article, the reader should be able to: Describe the recommended treatment of pulseless ventricular arrhythmias as outlined in the 2000 revision of the American Heart Association (AHA) Advanced Cardiac Life Support (ACLS) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (“guidelines”). Compare the benefits of drugs used for the treatment of ventricular arrhythmias. Use this information in a clinical setting. Dr. Rea is on the speakers bureau of Sancfi Aventis. Dr. Seybert was/is the recipient of direct grant/research funds from Abbott and KOS and is/was on the speakers bureau of The Medicine Company, Millenium, Merck, and Wyeth. All of the remaining authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining to this educational activity. Lippincott CME Institute, Inc., has identified and resolved all faculty conflicts of interest regarding this educational activity. Visit the Critical Care Medicine Web site (www.ccmjournal.org) for information on obtaining continuing medical education credit.

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.

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.