Voriconazole Sequestration During Extracorporeal Membrane Oxygenation for Invasive Lung Aspergillosis: A Case Report.

The increasing use of extracorporeal membrane oxygenation (ECMO) in critical care introduces new challenges with medication dosing. Voriconazole, a commonly used antifungal and the first-choice agent for the treatment of invasive aspergillosis, is a poorly water-soluble and highly protein-bound drug. Significant sequestration in ECMO circuits can be expected; however, no specific dosing recommendations are available. We report on the therapeutic drug monitoring and clinical evolution of a patient treated with voriconazole for invasive pulmonary aspergillosis while receiving ECMO therapy. Voriconazole trough levels were persistently low (<1 µg/mL) after initiation of ECMO despite additional loading doses and dose increases. Voriconazole dose had to be increased to 6.5 mg/kg three times daily to obtain therapeutic trough levels. The inability to achieve therapeutic levels of voriconazole for a prolonged period (a minimum of 9 days) while undergoing ECMO therapy is believed to have been a significant contributing factor in the patient's fatal outcome. Therapeutic trough levels of voriconazole cannot be guaranteed with standard dosing in patients undergoing ECMO and much higher doses may be necessary. Empirical use of higher doses and/or combination therapy may be reasonable and frequent therapeutic drug monitoring is mandatory.

Antipsychotic Drug Use and Screening for Delirium in Mechanically Ventilated Patients in Canadian Intensive Care Units: An Observational Study.

BACKGROUND: Critically ill patients frequently experience delirium, and antipsychotic drugs are often used to manage symptoms. OBJECTIVES: To describe the use of antipsychotic drugs and delirium screening tools in mechanically ventilated, critically ill adult patients in Canadian intensive care units (ICUs) and to identify factors associated with the use of antipsychotic drugs. METHODS: Pharmacists from 51 Canadian ICUs prospectively collected data on antipsychotic use and delirium screening in all patients for whom invasive mechanical ventilation was initiated during a chosen 2-week period occurring sometime in 2008 or 2009. RESULTS: Data were collected for a total of 712 patients, of whom 115 (16.2%) received at least one dose of an antipsychotic. The antipsychotic prescribed, the total daily dose, and the administration schedule varied across sites. Delirium screening tools, validated for use in mechanically ventilated patients and endorsed by professional society guidelines, were part of routine care in a minority of ICUs (7/51 [13.7%]), and delirium screening was documented for few patients overall (41/712 patients [5.8%]). In a multivariable analysis, administration of antipsychotics was independently associated with longer duration of mechanical ventilation (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.07-1.17), daily interruption of sedation (OR 1.71, 95% CI 1.01-2.90), and use of physical restraints (OR 2.15, 95% CI 1.27-3.65). CONCLUSION: A minority of mechanically ventilated patients in Canadian ICUs received antipsychotic drugs, and screening for delirium with validated tools was rare. Antipsychotic drug use was independently associated with longer duration of mechanical ventilation, daily interruption of sedation, and use of physical restraints.

CONTEXTE: Les patients gravement malades souffrent fréquemment de délire, une affection dont les symptômes sont souvent traités à l'aide d'antipsychotiques. OBJECTIFS: Dresser le portrait de l'utilisation des antipsychotiques et des outils de dépistage du délire chez les patients adultes gravement malades sous ventilation mécanique ayant séjourné dans une unité de soins intensifs (USI) canadienne et relever les facteurs associés à l'utilisation des antipsychotiques. MÉTHODES: Des pharmaciens de 51 USI canadiennes ont recueilli des données de façon prospective sur l'utilisation des antipsychotiques et sur le dépistage de cas de délire auprès de tous les patients placés sous ventilation mécanique effractive au cours d'une période de deux semaines entre 2008 et 2009. RÉSULTATS: Les données ont été recueillies chez un total de 712 patients. De ce nombre, 115 (16,2 %) ont reçu au moins une dose d'un antipsychotique. L'antipsychotique prescrit, la posologie quotidienne et l'horaire d'administration variaient d'un établissement à l'autre. Des outils de dépistage du délire (dont l'emploi est validé chez les patients sous ventilation mécanique et approuvé dans les lignes directrices d'associations professionnelles) ne faisaient partie des soins habituels que dans un petit nombre d'USI (7/51 [13,7 %]). De plus, les dépistages du délire n'ont été consignés que pour peu de patients dans l'ensemble (41/712 patients [5,8 %]). Au cours d'une analyse multivariable, on a associé indépendamment l'administration d'antipsychotiques à une durée accrue de la ventilation mécanique (risque relatif approché [RRA] de 1,12, intervalle de confiance [IC] à 95 % de 1,07­1,17), à une interruption quotidienne de la sédation (RRA de 1,71, IC à 95 % de 1,01­2,90) et à l'emploi de contention physique (RRA de 2,15, IC à 95 % de 1,27­3,65). CONCLUSIONS: Seul un petit nombre de patients sous ventilation mécanique ayant séjourné dans une USI canadienne ont reçu des antipsychotiques; de plus, des outils validés de dépistage du délire n'ont que rarement été employés. L'utilisation d'antipsychotiques a été indépendamment associée à une durée accrue de la ventilation mécanique, à l'interruption quotidienne de la sédation et à l'emploi de contention physique.

Use of probiotics to prevent ventilator-associated pneumonia: A survey of pharmacists' attitudes.

PURPOSE: The primary objective of this survey was to describe pharmacists' attitudes regarding probiotic use in the intensive care unit (ICU); secondary objectives were to evaluate pharmacists' knowledge and use of probiotics for critically ill patients. METHODS: The survey instrument was rigorously designed and pretested, then distributed in both English and French to Canadian ICU pharmacists. The online survey was open for 5 weeks, and 3 follow-up emails were sent to maximize response rates. RESULTS: Of 303 eligible surveys, 191 were returned (63.0%). Probiotics were available in the hospitals of 69.8% (113/162) of respondents, and 62.0% (101/163) indicated that they had used probiotics for at least 1 ICU patient in the previous year. Most pharmacists (137/171, 80.1%) said that they would "never" consider recommending probiotics for prevention of ventilator-associated pneumonia in ICU patients, and this response was more common (P = .0074) among pharmacists who were "unsure" about the safety of probiotics in this population when compared to those who felt that they knew how safe probiotics are. CONCLUSIONS: Most Canadian ICU pharmacists have used probiotics at least once in the ICU in the last year. However, based on uncertain efficacy and safety, most ICU pharmacists would not currently recommend probiotics for the prevention of ventilator-associated pneumonia.

Canadian survey of critical care pharmacists' views and involvement in clinical research.

BACKGROUND: The involvement of Canadian critical care pharmacists in clinical research is not well documented. OBJECTIVE: To describe the clinical research experience of Canadian critical care pharmacists, describe their views about clinical research, and identify factors that facilitate their involvement in clinical research. METHODS: A cross-sectional electronic survey of Canadian critical care pharmacists was developed through an iterative process and conducted from July to October 2010. We invited 325 pharmacists from 129 hospitals across Canada to participate. Surveys with more than 30% of questions unanswered were discarded. RESULTS: Analyzable response rate was 66.2%. Overall, 33 pharmacists (15.7%) were highly involved in research, 54 (25.7%) were moderately involved, and 123 (58.6%) were minimally involved. Most respondents (97.2%) believed that critical care pharmacist involvement in research was desirable, and many (80.4%) expressed interest to be more involved in research. Nearly all respondents (99.5%) agreed that more support should be provided to pharmacists interested in conducting research. Pharmacists currently involved in research have obtained higher academic degrees (adjusted OR 11.23; p < 0.001), express a strong interest in research (adjusted OR 7.44; p < 0.001), report a higher level of training for involvement in research (adjusted OR 2.23; p = 0.047), and practice more often in a university hospital (adjusted OR 3.68; p = 0.004) within an intensive care unit where involvement in research is valued (adjusted OR 5.61; p < 0.001). Support from pharmacy departments is not related to involvement in research (adjusted OR 1.22; p = 0.633). CONCLUSIONS: Canadian critical care pharmacists are involved to varying degrees in clinical research and are very interested in initiating and supporting research activities. Opportunities are present but significant barriers exist. The value of pharmacist-initiated research needs recognition as a priority within hospital pharmacy administration.

Current therapeutic uses, pharmacology, and clinical considerations of neuromuscular blocking agents for critically ill adults.

OBJECTIVE: To summarize literature describing use of neuromuscular blocking agents (NMBAs) for common critical care indications and provide a review of NMBA pharmacology, pharmacokinetics, dosing, drug interactions, monitoring, complications, and reversal. DATA SOURCES: Searches of MEDLINE (1975-May 2011), EMBASE (1980-May 2011), and Cumulative Index to Nursing and Allied Health Literature (1981-May 2011) were conducted to identify observational and interventional studies evaluating the efficacy or safety of NMBAs for management of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), status asthmaticus, elevated intracranial pressure (ICP), and therapeutic hypothermia. STUDY SELECTION AND DATA EXTRACTION: We excluded case reports, animal- or laboratory-based studies, trials describing NMBA use during rapid sequence intubation or in the operating room, and studies published in languages other than English or French. DATA SYNTHESIS: Clinical applications of NMBAs in intensive care include, but are not limited to, immobilizing patients for procedural interventions, decreasing oxygen consumption, facilitating mechanical ventilation, reducing intracranial pressure, preventing shivering, and management of tetanus. Recent data on ARDS demonstrated that early application of NMBAs improved adjusted 90-day survival for patients with severe lung injury. These results may lead to increased use of these drugs. While emerging data support the use of cisatracurium in select patients with ALI/ARDS, current literature does not support the use of one NMBA over another for other critical care indications. Cisatracurium may be kinetically preferred for patients with organ dysfunction. Close monitoring with peripheral nerve stimulation is recommended with sustained use of NMBAs to avoid drug accumulation and minimize the risk for adverse drug events. Reversal of paralysis is achieved by discontinuing therapy or, rarely, the use of anticholinesterases. CONCLUSIONS: NMBAs are high-alert medications used to manage critically ill patients. New data are available regarding the use of these agents for treatment of ALI/ARDS and status asthmaticus, management of elevated ICP, and provision of therapeutic hypothermia after cardiac arrest. To improve outcomes and promote patient safety, intensive care unit team members should have a thorough knowledge of this class of medications.