The Influence of Extracorporeal Membrane Oxygenation on Antibiotic Pharmacokinetics.

Extracorporeal membrane oxygenation (ECMO) is becoming increasingly utilized to support critically ill patients who experience life-threatening cardiac or pulmonary compromise. The provision of this intervention poses challenges related to its complications and the optimization of medication therapy. ECMO's mechanical circulatory support is facilitated via various devices and equipment that have been shown to sequester lipophilic- and protein-bound medications, including anti-infectives. Since infectious outcomes are dependent on achieving specific anti-infectives' pharmacodynamic targets, the understanding of these medications' pharmacokinetic parameters in the setting of ECMO is important to clinicians. This narrative, non-systematic review evaluated the findings of the most recent and robust pharmacokinetic analyses for commonly utilized anti-infectives in the setting of ECMO. The data from available literature indicates that anti-infective pharmacokinetic parameters are similar to those observed in other non-ECMO critically ill populations, but considerable variability in the findings was observed between patients, thus prompting further evaluation of therapeutic drug monitoring in this complex population.

Hydromorphone Compared to Fentanyl in Patients Receiving Extracorporeal Membrane Oxygenation.

Fentanyl is commonly used in critically ill patients receiving extracorporeal membrane oxygenation (ECMO). Fentanyl's lipophilicity and protein binding may contribute to a sequestration of the drug in the ECMO circuit. Hydromorphone lacks these characteristics potentially leading to a more predictable drug delivery and improved pain and sedation management among ECMO patients. This study compared hydromorphone to fentanyl in patients receiving ECMO. This retrospective study included adult patients receiving ECMO for ≥48 hours. Patients were excluded if they required neuromuscular blockade, received both fentanyl and hydromorphone during therapy, or had opioid use before hospitalization. Baseline characteristics included patient demographics, ECMO indication and settings, and details regarding mechanical ventilation. The primary outcome was opioid requirements at 48 hours post cannulation described in morphine milligram equivalent (MME). Secondary endpoints included 24-hour opioid requirements, concurrent sedative use, and differences in pain and sedation scores. No differences were noted between the patients receiving fentanyl (n = 32) or hydromorphone (n = 20). Patients receiving hydromorphone required lower MME compared to fentanyl at 24 hours (88 [37-121] vs. 131 [137-227], p < 0.01) and 48 hours (168 [80-281] vs. 325 [270-449], p < 0.01). The proportion of within-goal pain and sedation scores between groups was similar at 24 and 48 hours. Sedative requirements did not differ between the groups. Patients receiving hydromorphone required less MME compared to fentanyl without any differences in sedative requirements, or agitation-sedation scores at 48 hours. Prospective studies should be completed to validate these findings.

Major publications in the critical care pharmacotherapy literature: January-December 2014.

PURPOSE: Nine recently published articles and one guideline with important implications for critical care pharmacy practice are summarized. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) group includes more than 40 experienced critical care pharmacists across the United States. Group members monitor 29 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on applicability to practice, relevance, and study design and strength. Hundreds of relevant articles were evaluated by the group in 2014, of which 114 were summarized and disseminated to CCPLU group members. From among those 114 publications, 10 deemed to be of particularly high utility to the critical care practitioner were selected for inclusion in this review for their potential to change practice or reinforce current evidence-based practice. One of the selected articles presents updated recommendations on the management of patients with atrial fibrillation (AF); the other 9 address topics such as albumin replacement in patients with severe sepsis, use of enteral statins for acute respiratory distress syndrome, fibrinolysis for patients with intermediate-risk pulmonary embolism, the use of unfractionated heparin versus bivalirudin for primary percutaneous coronary intervention, and early protocol-based care for septic shock. CONCLUSION: There were many important additions to the critical care pharmacotherapy literature in 2014, including a joint guideline for the management of AF and reports of clinical trials.

Major publications in the critical care pharmacotherapy literature: January-December 2013.

PURPOSE: Ten recently published articles with important implications for critical care pharmacotherapy are summarized. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) group is a national assembly of experienced intensive care unit (ICU) pharmacists across the United States. Group members monitor 25 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on (1) applicability to critical care practice, (2) relevance to pharmacy practitioners, and (3) quality of evidence or research methodology. Hundreds of relevant articles were evaluated by the group during the period January-December 2013, of which 98 were summarized and disseminated nationally to CCPLU group members. Among those 98 publications, 10 deemed to be of particularly high utility to critical care practitioners were included in this review. The 10 articles address topics such as rapid lowering of blood pressure in patients with intracranial hemorrhage, adjunctive therapy to prevent renal injury due to acute heart failure, triple-drug therapy to improve neurologic outcomes after cardiac arrest, and continuous versus intermittent infusion of ß-lactam antibiotics in severe sepsis. CONCLUSION: There were many important additions to the critical care pharmacotherapy literature in 2013, including an updated guideline on the management of myocardial infarction and reports on advances in research focused on improving outcomes in patients with stroke or cardiac arrest and preventing the spread of drug-resistant pathogens in the ICU.

Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle.

OBJECTIVE: The debilitating and persistent effects of ICU-acquired delirium and weakness warrant testing of prevention strategies. The purpose of this study was to evaluate the effectiveness and safety of implementing the Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle into everyday practice. DESIGN: Eighteen-month, prospective, cohort, before-after study conducted between November 2010 and May 2012. SETTING: Five adult ICUs, one step-down unit, and one oncology/hematology special care unit located in a 624-bed tertiary medical center. PATIENTS: Two hundred ninety-six patients (146 prebundle and 150 postbundle implementation), who are 19 years old or older, managed by the institutions' medical or surgical critical care service. INTERVENTIONS: Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle. MEASUREMENTS AND MAIN RESULTS: For mechanically ventilated patients (n = 187), we examined the association between bundle implementation and ventilator-free days. For all patients, we used regression models to quantify the relationship between Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle implementation and the prevalence/duration of delirium and coma, early mobilization, mortality, time to discharge, and change in residence. Safety outcomes and bundle adherence were monitored. Patients in the postimplementation period spent three more days breathing without mechanical assistance than did those in the preimplementation period (median [interquartile range], 24 [7-26] vs 21 [0-25]; p = 0.04). After adjusting for age, sex, severity of illness, comorbidity, and mechanical ventilation status, patients managed with the Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle experienced a near halving of the odds of delirium (odds ratio, 0.55; 95% CI, 0.33-0.93; p = 0.03) and increased odds of mobilizing out of bed at least once during an ICU stay (odds ratio, 2.11; 95% CI, 1.29-3.45; p = 0.003). No significant differences were noted in self-extubation or reintubation rates. CONCLUSIONS: Critically ill patients managed with the Awakening and Breathing Coordination, Delirium monitoring/management, and Early exercise/mobility bundle spent three more days breathing without assistance, experienced less delirium, and were more likely to be mobilized during their ICU stay than patients treated with usual care.

Top 10 myths regarding sedation and delirium in the ICU.

The management of pain, agitation, and delirium in critically ill patients can be complicated by multiple factors. Decisions to administer opioids, sedatives, and antipsychotic medications are frequently driven by a desire to facilitate patients' comfort and their tolerance of invasive procedures or other interventions within the ICU. Despite accumulating evidence supporting new strategies to optimize pain, sedation, and delirium practices in the ICU, many critical care practitioners continue to embrace false perceptions regarding appropriate management in these critically ill patients. This article explores these perceptions in more detail and offers new evidence-based strategies to help critical care practitioners better manage sedation and delirium, particularly in ICU patients.

Critical care nurses' role in implementing the "ABCDE bundle" into practice.

Imagine working in an environment where all patients undergoing mechanical ventilation are alert, calm, and delirium free. Envision practicing in an environment where nonvocal patients can effectively express their need for better pain control, repositioning, or emotional reassurance. Picture an intensive care unit where a nurse-led, interprofessional team practices evidence-based, patient-centered care focused on preserving and/or restoring their clients' physical, functional, and neurocognitive abilities. A recently proposed bundle of practices for the intensive care unit could advance the current practice environment toward this idealized environment. The Awakening and Breathing Coordination, Delirium Monitoring and Management, and Early Mobility (ABCDE) bundle incorporates the best available evidence related to delirium, immobility, sedation/analgesia, and ventilator management in the intensive care unit for adoption into everyday clinical practice.

High-dose argatroban for treatment of heparin-induced thrombocytopenia with thrombosis: a case report and review of laboratory considerations.

PURPOSE: A case report describing high-dose argatroban for the treatment of heparin-induced thrombocytopenia (HIT) with thrombosis and associated considerations in interpreting laboratory monitoring data are presented. SUMMARY: A 51-year-old woman with an extensive history of coronary artery disease arrived at the emergency department with complaints of chest pain. The patient was admitted, and coronary artery bypass graft surgery was ultimately performed. The patient had a baseline platelet count of 177,000 cells/µL. During hospitalization, the patient received heparin, and her platelet count dropped to 12,000 cells/µL 13 days after the initiation of heparin. The patient developed swelling around a peripherally inserted central catheter and later developed deep vein thrombosis. An argatroban infusion of 2 µg/kg/min was initiated, with a target activated partial thromboplastin time (aPTT) of 40-80 seconds. After 5 days of therapy, the patient had increased swelling in her right arm and an aPTT of 56 seconds. Her goal aPTT was subsequently increased. Six days later, the patient developed a left-lower-extremity DVT despite aPTTs within the goal range. A new aPTT target of >75 seconds was set. The infusion rate was increased to 15.5 µg/kg/min to attain the target aPTT. Results of an in vitro test led to an alternative interpretation of aPTT and International Normalized Ratio values that aided in the monitoring of argatroban during the high-dose infusion. CONCLUSION: A patient with HIT with thrombosis was successfully treated with unusually high dosages of argatroban and may have had serum argatroban concentrations exceeding what has commonly been thought to be the therapeutic range.

Sapropterin: a new therapeutic agent for phenylketonuria.

OBJECTIVE: To summarize the role of pharmacotherapy in the management of phenylketonuria (PKU) and to review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile of sapropterin for this indication. DATA SOURCES: A literature search was conducted using MEDLINE (1966-May 2009), International Pharmaceutical Abstracts (1970-May 2009), and Cochrane database (2008) for the following key words: sapropterin, tetrahydrobiopterin, phenylketonurias, and phenylalanine. STUDY SELECTION AND DATA EXTRACTION: English-language studies involving humans examining the role of tetrahydrobiopterin (BH4) in the management of PKU were reviewed to evaluate the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and safety profile for sapropterin. All Phase 2 and 3 randomized controlled trials assessing the safety and efficacy of sapropterin were included in this literature evaluation. DATA SYNTHESIS: Sapropterin represents the only Food and Drug Administration-approved medication for BH4-responsive PKU, marking an important advance in the treatment of this condition. Among individuals with hyperphenylalaninemia and some residual phenylalanine hydroxylase function, sapropterin can enhance activity of this enzyme to decrease serum phenylalanine concentrations. Sapropterin has been compared with placebo in one Phase 2 and one Phase 3 clinical trial, demonstrating significantly better response rates. Based on available studies, this agent appears to be safe and well tolerated, with adverse event rates similar to those of placebo. However, additional studies are warranted to assess the long-term safety and efficacy of sapropterin therapy. CONCLUSIONS: Sapropterin offers a promising therapeutic option for select individuals with BH4-responsive PKU, although long-term data are limited evaluating its safety and efficacy in traditional clinical practice settings. When considering sapropterin therapy, clinicians must consider factors such as cost and patient adherence to drug therapy and/or diet.

Aliskiren-induced QT interval prolongation.

Aliskiren gained FDA approval for the treatment of hypertension in 2007. It is the first approved pharmaceutical to manage hypertension by direct renin inhibition. With the introduction of novel drugs and mechanisms of action comes the challenge of monitoring for new unreported adverse events. The side effect profile for aliskiren has not yet been fully described. We describe the first apparent report of aliskiren-induced QT prolongation resulting in torsades de pointes.

Repeated bowel perforations with Ibuprofen lysine: a case report.

Non-steroidal anti-inflammatory drugs (NSAID) have been used to close the patent ductus arteriosus in neonates for over two decades. Ibuprofen lysine, a parenteral NSAID, is labeled for the treatment of patent ductus arteriosus in neonates who do not respond to conventional medical management. While sharing many of the same adverse effects as indomethacin, spontaneous bowel perforation has not been reported. We describe a premature infant that experienced isolated bowel perforations after treatment with ibuprofen lysine for symptomatic patent ductus arteriosus.