Assessment and Impact of Intravenous Medication Fluid Administration in Critically Ill Patients With Acute Respiratory Failure.

BACKGROUND: Positive fluid balance early in critical illness is associated with poor outcomes. Reducing intravenous medication volume may mitigate volume overload. Objective: Assessment of fluid and medication administration and clinical outcomes in acute respiratory failure. METHODS: Single-center, prospective observational study of hemodynamically stable adult patients in a medical intensive care unit (MICU) with acute respiratory failure. RESULTS: Median cumulative total intake volume was 12 890 (interquartile range [IQR] = 8654-22 221) mL (n = 27), and median cumulative intravenous medication volume was 3563 (IQR = 2371-9412) mL over the first 7 days. Medication volume accounted for 27.6% of aggregate fluid volume. Median daily intravenous medication volume administered was 591 (IQR = 339-1082) mL. Cumulative fluid volume was associated with reduced ventilator-free days (r2 = -0.393; P = 0.043), and cumulative fluid volumes during the first 3 and 7 days were associated with increased MICU length of stay (LOS ± standard error 0.73 ± 0.35 d/L, P = 0.047, and 0.38 ± 0.16 d/L, P = 0.021, respectively). Cumulative medication volume administered significantly reduced the likelihood of mechanical ventilator liberation (hazard ratio [HR] = 0.917; 95% CI: 0.854, 0.984; P = 0.016) and MICU discharge (HR = 0.911; 95% CI: 0.843, 0.985; P = 0.019). Small-volume infusion may decrease cumulative intravenous medication volume by 38%. CONCLUSION AND RELEVANCE: Intravenous medication diluent contributes substantially to total fluid intake in patients with acute respiratory failure and is associated with poor outcomes. Reduction of intravenous medication fluid volume to improve clinical outcomes should be further investigated.

Continuation of Opioid Therapy at Transitions of Care in Critically Ill Patients.

PURPOSE: Opioids are one of the high-risk medication classes that are administered to critically ill patients during their intensive care unit (ICU) stay. However, little attention has been given to inpatient opioid prescribing practices, especially in critically ill patients. The purpose of our study was to characterize opioid prescribing practices across 2 transitions of care during an inpatient hospital stay: medical ICU (MICU)/intermediate care unit (IMC) to floor and floor to hospital discharge and identify potential patient-specific factors that impact opioid continuation. METHODS: This is a retrospective cohort study evaluating opioid-naive adult patients with new opioid therapy initiated in MICU/IMC at a tertiary care academic medical center from December 1, 2016, to November 30, 2017. Opioid continuation rate was assessed twice: transition 1 (MICU/IMC to floor) and transition 2 (floor to hospital discharge). RESULTS: In total, 112 opioid-naive patients with initial opioid administration in the MICU/IMC were included. Opioid therapy was continued in 56.1% (37/66) at transition 1 and 56.8% of patients (21/37) at transition 2. Patients with opioids continued at transition 1 had a longer hospital length of stay compared to those not continued on opioids, 22 (interquartile range [IQR] 11-36) vs 8 (IQR 6-14; P = .0004). Among the patients continued on opioids at hospital discharge, intubation during hospital stay and cumulative opioid dosage were greater than those not continued on opioids (17 [80.9%] vs 7 [43.8%], P = .019; and 3482 mcg [IQR 1690-9530] vs 732.5 mcg [IQR 187.5-1360.9], P = .0018, respectively). CONCLUSIONS: Opioid-naive patients receiving opioid therapy in the MICU/IMC had a continuation rate of >56% during transitions of care, including hospital discharge. Factors that contributed to the continuation of opioids at transitions of care included longer hospital length of stay, intubation, and cumulative hospital opioid dosage. These findings may help to provide health systems with guidance on targeted opioid stewardship programs.

Vancomycin Pharmacokinetics in Obese Patients with Sepsis or Septic Shock.

STUDY OBJECTIVES: Obese patients with sepsis or septic shock may have altered vancomycin pharmacokinetics compared with the general population that may result in improper dosing or inadequate drug concentrations. The objective of this study was to characterize vancomycin pharmacokinetics in obese patients with sepsis or septic shock, and to develop a novel pharmacokinetic dosing model based on pharmacokinetic-pharmacodynamic target requirements. DESIGN: Prospective observational pharmacokinetic study. SETTING: Large quaternary academic medical center. PATIENTS: Sixteen obese (body mass index [BMI] 30 kg/m2 or higher) adults with sepsis and either a gram-positive bacteremia or requiring vasopressor support (septic shock), who were receiving vancomycin between November 2016 and June 2018, were included. Patients were excluded if they were receiving renal replacement therapy or extracorporeal membrane oxygenation, treatment for central nervous system infections, pregnant, or receiving vancomycin for surgical prophylaxis. INTERVENTION: Four blood samples per patient were collected following a single dose of vancomycin: one peak serum vancomycin level (within 1-2 hrs of infusion completion), two random levels during the dosing interval, and one trough level (within 30-60 min of the next dose) were measured. MEASUREMENTS AND MAIN RESULTS: A population pharmacokinetic model was developed to describe vancomycin concentrations over time. Simulations to determine optimal dosing were performed using the pharmacokinetic model with different ranges of creatinine clearance (Clcr ) and different vancomycin daily doses. Median age of the patients was 62 years; median BMI was 36.1 kg/m2 , Acute Physiology and Chronic Health Evaluation II score was 26, and Sequential Organ Failure Assessment score was 11. Eleven patients (69%) had an acute kidney injury. Median initial vancomycin dose was 15 mg/kg; median vancomycin trough concentration was 17 mg/L. A one-compartment model best characterized the pharmacokinetics of vancomycin in obese patients with sepsis or septic shock. Volume of distribution was slightly increased in this population (0.8 L/kg) compared with the general population (0.7 L/kg). Only Clcr effect on drug clearance was found to be significant (decrease in the objective function value by 16.4 points), confirming that it is a strong predictor of vancomycin clearance. CONCLUSION: To our knowledge, this study provides the first population-based pharmacokinetic model in obese patients with sepsis or septic shock. The nomograms generated from this pharmacokinetic model provide a simplified approach to vancomycin dosing in this patient population.

Antimicrobial Therapy in Septic Shock Is Conservative During Resuscitation and Maintenance Phases.

Background: Maximal dosing of early antimicrobials with high loading and maintenance doses may optimize pharmacokinetic parameters to achieve and maintain therapeutic concentrations at the site of infection in septic shock. Little is known about the current practice of early antimicrobial dosing in septic shock. Objective: To characterize early antimicrobial dosing in patients in the resuscitation phase of septic shock. Methods: This retrospective cohort study included patients admitted to the medical intensive care unit (ICU) with septic shock. The primary outcome was the percentage of early antibiotic orders that were maximal or conservative during the resuscitation (0 to 48 hours) phase based on predefined dosing criteria. The secondary outcomes were the correlations of different dosing strategies on hospital length of stay (LOS), ICU LOS, and hospital mortality. Results: This study evaluated 161 patients and 692 antibiotic orders; 504 (72.8%) of the orders during the resuscitation phase were conservative. There were no differences in mortality (odds ratio = 0.66; 95% confidence interval = 0.35-1.25; P = .20), hospital LOS (median = 20 [interquartile range (IQR) = 10-34] vs 19 [IQR = 11-32] days; P = .93), or ICU LOS (median = 8 [IQR = 5-16] vs 9 [IQR = 5-15] days; P = .63) between maximal and conservative dosing groups, respectively, in the resuscitation phase. Limitations of this study included the use of institution-specific antimicrobial dosing guidelines and its retrospective nature. Conclusions: Early antibiotic dosing is conservative for a majority of patients in septic shock. Future studies are needed to evaluate the impact of dosing strategy on patient-centered outcomes in septic shock.

Professional Benefits of a Web-based Journal Club for Critical Care Residents and Their Mentors.

Objective. To identify the perceptions and benefits of participation in a web-based journal club by the critical care pharmacy residents who presented and their mentors. Methods. Former and current resident presenters and their mentors were invited to complete one of three electronic surveys created to assess their perceptions of their experiences with a web-based journal club sponsored by the Clinical Pharmacy and Pharmacology (CPP) Section of the Society of Critical Care Medicine (SCCM). Descriptive statistics were used to analyze the data gathered. Results. Thirty-eight (41%) former residents, 23 (72%) recent or current residents, and 32 (58%) presentation mentors responded to the survey. Residents in both groups indicated that participation was a beneficial educational and professional experience. Residents who more recently presented an online journal club reported improved confidence in critically evaluating research, determining clinical applications of published literature, developing evidence-based recommendations, and educating trainees on evidence-based medicine. Mentors believed their residents' journal club participation influenced their future involvement in both the SCCM and the CPP Section and were extremely likely to recommend their future residents participate in the web-based journal club. Conclusion. Participation in a web-based journal club provided professional benefits to participants and their mentors that extended beyond the presentation itself. Interaction with the organization through this experience may have encouraged these individuals to maintain their professional involvement in the organization after the web-based journal club experience was completed. Other professional organizations may benefit from implementation of a similar web-based journal club.

Moderate to Severe Acute Respiratory Distress Syndrome Management Strategies: A Narrative Review.

Acute respiratory distress syndrome (ARDS) remains a common complication associated with significant negative outcomes in critically ill patients. Lung-protective mechanical ventilation strategies remain the cornerstone in the management of ARDS. Several therapeutic options are currently available including fluid management, neuromuscular blocking agents, prone positioning, extracorporeal membrane oxygenation, corticosteroids, and inhaled pulmonary vasodilating agents (prostacyclins and nitric oxide). Unfortunately, an evidence-based, standard-of-care approach in managing ARDS beyond lung-protective ventilation remains elusive, contributing to significant variability in clinical practice. Although the optimal therapeutic strategy for managing moderate to severe ARDS remains extremely controversial, therapies supported with more robust clinical evidence should be considered first. The purpose of this narrative review is to discuss the published clinical evidence for both pharmacologic and nonpharmacologic management strategies in adult patients with moderate to severe ARDS as well as to discuss practical considerations for implementation.

Impact of an Antipsychotic Discontinuation Bundle During Transitions of Care in Critically Ill Patients.

INTRODUCTION:: Delirium affects a large proportion of patients admitted to the intensive care unit (ICU) and is associated with increased morbidity and mortality. Antipsychotics have become frequently used agents for the treatment of delirium; however, they are often continued at transitions of care. This has potential negative short- and long-term health consequences that are preventable. We investigated the antipsychotic tapering bundle's impact on the rate of antipsychotic continuation at transitions from the medical intensive care unit (MICU). METHODS:: This was a preretrospective and postretrospective chart review that included adult patients in the MICU initiated on antipsychotic therapy for ICU delirium. A bundled multidisciplinary education program and antipsychotic discontinuation algorithm were implemented in the MICU to provide recommendations for safe and effective use of antipsychotics for ICU delirium and minimize continuation of therapy at transitions of care. Rates of antipsychotic continuation at transition from the MICU were compared between the preintervention and postintervention groups with the χ2 test. RESULTS:: A total of 140 patients in the prebundle group and 141 patients in the postbundle group were enrolled. Overall, baseline characteristics were similar. After implementation of the discontinuation bundle, antipsychotic continuation at MICU discharge decreased (27.9% in the prebundle group vs 17.7% in the postbundle group; P < .05). In the multivariate analysis, patients were less likely to be continued on antipsychotic therapy at MICU discharge after implementation of the bundle (odds ratio [OR]: 0.47; 95% confidence interval [CI]: 0.26-0.86). There were also lower rates of overall antipsychotic continuation at hospital discharge (OR: 0.4; 95% CI: 0.18-0.89). CONCLUSION:: This is the first study to demonstrate a reduction in antipsychotic continuation at transition from the MICU after implementation of an antipsychotic discontinuation bundle in ICU patients. We believe this bundle allows for safer transitions of care from the MICU and decreases unnecessary antipsychotic therapy.

Pharmacokinetic and Pharmacodynamic Considerations of Antibiotics of Last Resort in Treating Gram-Negative Infections in Adult Critically Ill Patients.

PURPOSE OF REVIEW: We provide an overview of antimicrobials that are considered last resort for the treatment of resistant gram-negative infections in adult critically ill patients. The role in therapy, pharmacodynamic (PD) goals, and pharmacokinetic (PK) changes in critical illness for aminoglycosides, polymyxins, tigecycline, fosfomycin, and fluoroquinolones are summarized. RECENT FINDINGS: Altered PK in septic patients in the intensive care unit (ICU) is observed with many of our agents of last resort. Based on the available literature, dosage adjustments may be required to optimize PK parameters and meet PD targets for most effective bacterial killing. Data is limited, studies are conducted in heterogeneous patient populations, and conclusions are frequently conflicting. Strategic dosing regimens such as high-dose extended interval dosing of aminoglycosides or loading doses with colistin and polymyxin B are examples of ways to optimize antibiotic PK in critically ill patients. Benefits of these strategies must be balanced with risks of increased toxicity. Patients with resistant gram-negative infections may present with septic shock in the ICU. Sepsis can significantly alter the PK of antibiotics and require dosage adjustments to attain optimal drug levels. An understanding of PK and PD properties of these agents of last resort will help to maximize therapeutic efficacy while minimizing toxic effects.

Pharmacokinetic/Pharmacodynamic Considerations of Beta-Lactam Antibiotics in Adult Critically Ill Patients.

PURPOSE OF REVIEW: Beta-lactam antibiotics are commonly prescribed in critically ill patients for a variety of infectious conditions. Our understanding of how critical illness alters beta-lactam pharmacokinetics/pharmacodynamics (PK/PD) is rapidly evolving. RECENT FINDINGS: There is a growing body of literature in adult patients demonstrating that physiological alterations occurring in critically ill patients may limit our ability to optimally dose beta-lactam antibiotics to reach these PK/PD targets. These alterations include changes in volume of distribution and renal clearance with multiple, often overlapping causative pathways, including hypoalbuminemia, renal replacement therapy, and extracorporeal membrane oxygenation. Strategies to overcome these PK alterations include extended infusions and therapeutic drug monitoring. Combined data has demonstrated a possible survival benefit associated with extending beta-lactam infusions in critically ill adult patients. This review highlights research on physiological derangements affecting beta-lactam concentrations and strategies to optimize beta-lactam PK/PD in critically ill adults.

Impact of diabetic ketoacidosis management in the medical intensive care unit after order set implementation.

OBJECTIVE: To determine the rate of compliance to the 2006 and 2009 ADA DKA guidelines in the medical intensive care unit (MICU) at a large academic medical centre after the implementation of a computerised DKA order set and protocol. METHODS: Retrospective chart review of adult patients with DKA admitted to the MICU. Results of pre-order set (PRE) were compared to those of data post-order set (POST). The primary outcome was a composite administration of intravenous fluid resuscitation in the first 24 h, insulin bolus and initial insulin infusion rate. KEY FINDINGS: Twelve of 60 patients (20%) in the PRE group received treatment compliant with the 2006 guidelines versus 14 of 55 patients (25.5%) in the POST group (OR 1.22 95% CI 0.44 to 3.4, P = 0.51). Compliance to the 2009 guidelines was significantly higher in the POST group (31.7% versus 65.5%, OR 4.44 95% CI 1.8 to 10.92, P = 0.0004). Compliance for individual components was 26.7% versus 70.9% for fluid resuscitation (P = 0.0001), 55% versus 49.1% for insulin bolus (P = 0.58) and 60% versus 81.3% for initial insulin infusion rate (P = 0.014), respectively. Time to DKA resolution was decreased (P = 0.04), and hypoglycaemia was increased (P = 0.0022). CONCLUSION: Implementation of a computerised DKA order set and protocol was associated with improved compliance to the 2009 ADA DKA guidelines, 24-h fluid resuscitation, initial insulin infusion rate, time to DKA resolution and appropriate transition to subcutaneous insulin. However, patients in the POST implementation group were more likely to exhibit hypoglycaemia. Future assessment is warranted.

Development of the Critical Care Pharmacotherapy Trials Network.

PURPOSE: The development of the Critical Care Pharmacotherapy Trials Network (CCPTN) as a model for practice-based pharmacotherapy research is described. SUMMARY: The CCPTN was formed in 2010 as a collaborative research network dedicated to scientific investigation in the field of critical care pharmacotherapy. The CCPTN organizational structure is consistent with many professional pharmacy and interdisciplinary organizations and organized into 3 primary domains: executive committee, working committees, and network membership. The network membership consists of critical care investigators dedicated to the mission and vision of the CCPTN and is open to anyone expressing an interest in contributing to high-level research. Network member sites represent the breadth of U.S. critical care practice environments. In addition, network members include individuals with demonstrated expertise in patient safety, administration, research design, grantsmanship, database management, peer review, and scientific writing. In 2015, there were more than 100 site investigators from around the United States and Canada. Projects to date have yielded numerous abstracts, platform presentations, and peer-reviewed publications in high-impact journals. The CCPTN has expanded to form collaborations with researchers in the United Kingdom, Australia, and New Zealand. The CCPTN has identified new potential partnerships and field-based areas for inquiry. Numerous opportunities for continued growth and scientific inquiry in the field of critical care pharmacotherapy research exist for the CCPTN to foster in the coming years. CONCLUSION: The CCPTN has been a successful model for practice-based pharmacotherapy research and assists its members in expanding critical care pharmacotherapy knowledge.

Clinical characteristics of critically ill patients with suspected influenza during the 2009-10 and 2013-14 outbreaks.

PURPOSE: Pandemic influenza A pdm09 (pH1N1) virus was the predominant isolate identified during the 2009-10 and 2013-14 influenza outbreaks, causing significant morbidity and mortality. We describe clinical characteristics of critically ill patients during 2 pH1N1 outbreaks. METHODS: Single-center, retrospective cohort study of patients admitted to the intensive care unit receiving oseltamivir for suspected influenza during 2 outbreak periods. Demographics and comorbidities were collected from the medical record. Outcomes included use of adjunct oxygenation therapies and oseltamivir dosing. RESULTS: One hundred twenty-four patients were included (2009, n=53; 2013, n=71). Demographics were as follows: mean (SD) age, 52.3 (14.2) years; mean (SD) Acute Physiology and Chronic Health Evaluation II score, 19.4 (9.2); 71% had greater than or equal to 2 comorbidities; and mortality was 27%. Inhaled nitric oxide was administered more commonly in 2009 (P=.01), whereas neuromuscular blockade (P=.02) and epoprostenol were administered more commonly in 2013 (P=.01). Patients in 2009 were more likely to receive high-dose oseltamivir (P=.02; odds ratio, 1.8; 95% confidence interval, 1.18-6.62). No differences in clinical outcomes were observed between 2009 and 2013. CONCLUSIONS: Use of adjunct oxygenation therapies and nontraditional antiviral dosing has changed significantly since the 2009 pandemic, although this has not resulted in a measurable impact on clinical outcomes.

Ceftolozane-Tazobactam Pharmacokinetics in a Critically Ill Patient on Continuous Venovenous Hemofiltration.

Extended-infusion ceftolozane-tazobactam treatment at 1.5 g every 8 h was used to treat multidrug-resistant Pseudomonas aeruginosa in a critically ill patient on continuous venovenous hemofiltration. Serum drug concentrations were measured at 1, 4, 5, 6, and 8 h after the start of infusion. Prefilter levels of ceftolozane produced a maximum concentration of drug (Cmax) of 38.57 µg/ml, concentration at the end of the dosing interval (Cmin) of 31.63 µg/ml, time to Cmax (Tmax) of 4 h, area under the concentration-time curve from 0 to 8 h (AUC0-8) of 284.38 µg · h/ml, and a half-life (t1/2) of 30.7 h. The concentrations were eight times the susceptibility breakpoint for the entire dosing interval.

Hospital delirium treatment: Continuation of antipsychotic therapy from the intensive care unit to discharge.

PURPOSE: The rate of continuation of antipsychotics for the management of delirium during hospital transitions of care in a tertiary care medical center was investigated. METHODS: A retrospective chart review was conducted for adult patients admitted to the medical intensive care unit (MICU) between June 1, 2011, and May 31, 2012, who were initiated on antipsychotic therapy at least 24 hours before transfer out of the MICU. The primary outcome evaluated was the percentage of patients initiated on an antipsychotic in the MICU who were continued on therapy after transfer to a medical ward. Secondary outcomes included the appropriateness of continuing antipsychotic therapy during transitions of care and the percentage of patients continued on an antipsychotic after hospital discharge. RESULTS: Of the 87 patients who met the study inclusion criteria, 23 (26%) were continued on antipsychotic therapy after their transfer from the MICU to the medical ward. Of the 23 patients continued on antipsychotic therapy, 9 (39%) were discharged from the hospital with an antipsychotic. Fourteen of the 23 patients were eligible for assessment of inappropriate antipsychotic continuation upon transfer from the MICU. Of these 14 patients, 9 (64%) were inappropriately continued on an antipsychotic. Patients continued on antipsychotic therapy at hospital discharge were more likely to be discharged to a facility (rehabilitation, skilled nursing facility, or healthcare institution) (p = 0.049).Future areas for study should include (1) prospective analysis to understand the clinical decision-making of providers when treating delirium, (2) evaluation of the long-term impact of continuing antipsychotic therapy for delirium, and (3) ways to improve communication of medication regimens during transitions of care. Plans to reduce antipsychotic continuation could involve reassessing patients on the medical wards, improving documentation of the indication for use in the medical record, or developing protocols to taper off antipsychotics before patients are discharged from the hospital. CONCLUSION: The continuation of antipsychotics for the management of delirium during transitions of care was a common practice at a tertiary care medical center. Patients receiving antipsychotics for treatment of delirium in the MICU were inappropriately continued on these agents when transferred from the MICU to the medical floor or discharged from the hospital.

Changes in Perceptions and Attitudes of Healthcare Profession Students Pre and Post Academic Course Experience of Team-Based 'Care for the Critically Ill'.

The aim of this study was to describe the development and outcomes of an interprofessional course "Interprofessional Care of the Critically Ill," involving pharmacy, nursing, social work, and respiratory therapy students from two universities. An institutional review board-approved survey was adapted from the TeamSTEPPS surveys investigating clinical practitioners' attitudes and perceptions regarding teamwork, collaboration, and interprofessional engagement. Items applicable to an academic setting were revised and resulted in a 28-statement survey and comments section. Participation was voluntary, and students were requested to participate in the survey on the first and last day of class. There was a significant increase in the perceived understanding of scope of practice of other disciplines from the beginning to end of class (24.4 to 60%, strongly agreed/agreed). Furthermore, students gained appreciation for the complexities associated with working in an interprofessional team with a significant increase in the percent agreeing and strongly agreeing that working on an interdisciplinary team is challenging (66.7 to 81%). Students and faculty gained a greater understanding and appreciation for other disciplines represented in the class and are therefore better prepared to engage in health care teams upon graduation. IPE should be embedded in curriculums and not just an add-on.

The pharmacologic treatment of intensive care unit delirium: a systematic review.

OBJECTIVE: To systematically evaluate the treatment of ICU delirium. DATA SOURCES: Literature searches were conducted using PubMed and Ovid MEDLINE (January 1980 to March 2013). Clinical trials/reports evaluating the use of pharmacologic treatment for ICU delirium were selected. References from major guidelines and publications were reviewed. STUDY SELECTION AND DATA EXTRACTION: English-language articles related to the treatment of ICU delirium were included. The following were excluded: (1) used pharmacologic treatment for the prevention of delirium; (2) inclusion of non-critically ill, palliative care, or hospice care patients; (3) letters to the editor; (4) case studies; (5) case series; (6) studies without delirium-related end points; and (7) studies with a predominantly postoperative population. Data extracted included: study design, population, treatment, number of participants, end points, outcomes/authors' conclusions, and adverse effects. DATA SYNTHESIS: Four studies were included in this review. The US Preventative Services Task Force classification scheme was used to assess the quality of evidence. All 4 studies reviewed were level I evidence studies. There are few well-designed, randomized studies that evaluate ICU delirium treatment. The 2 main randomized studies have small sample sizes and methodological concerns. Antipsychotic therapy may reduce the duration of ICU delirium. However, more robust studies are needed to demonstrate benefit. CONCLUSIONS: There is a lack of evidence supporting pharmacologic treatment for ICU delirium. Prospective, well-designed studies using proper delirium identification tools and severity are necessary to confirm the overall impact of pharmacologic therapy on the duration of delirium and associated complications.

Intravenous lipid emulsion in the management of amlodipine overdose.

OBJECTIVE: To report a case of amlodipine overdose successfully treated with intravenous lipid emulsion (ILE). CASE SUMMARY: A 47-year-old, 110 kg female ingested at least 350 mg of amlodipine with an unknown amount of ethanol. Initial blood pressure was 103/57 mm Hg, mean arterial pressure (MAP) 72 mm Hg, and heart rate 113 beats per minute. In the early clinical course, activated charcoal, intravenous fluid, and calcium boluses were administered. Worsening hypotension prompted a 100 mL bolus of 20% ILE. Stable hemodynamics were maintained for 2 hours. Subsequently, profound hypotension and shock developed (MAP 38 mm Hg), which failed to fully respond to 3 vasopressor agents, calcium, and glucagon. With continuing shock despite optimized vasopressors, an infusion of 2,300 mL 20% ILE was administered over 4.5 hours (20.9 mL/kg infusion total). By completion of the infusion, 2 vasopressors were tapered off and MAP remained above 70 mm Hg; within 12 hours, no further interventions were required. Possible adverse events of ILE, lipemia and hypoxia, were experienced but quickly resolved. The patient survived to hospital discharge within 8 days. DISCUSSION: Toxicity of amlodipine presents similar to distributive shock as both are due to marked peripheral vasodilation. There are numerous interventions in the management of amlodipine overdose, despite which many patients continue to suffer life-threatening shock as observed with this patient. ILE has been used with promising preliminary results as salvage therapy in case reports of other lipophilic molecules. This is the first report of lone amlodipine overdose treated with ILE. CONCLUSION: ILE is a novel antidote for overdoses of lipophilic substances and demonstrated efficacy in this case of amlodipine overdose without the use of hyperinsulinemic euglycemia.

Antipsychotics in the treatment of delirium in older hospitalized adults: a systematic review.

OBJECTIVES: To examine evidence of the efficacy of antipsychotics in the treatment of delirium in older hospitalized adults. DESIGN: Systematic literature review. SETTING: Hospital. PARTICIPANTS: Older adults with delirium. MEASUREMENTS: The MEDLINE (January 1980-December 2010) and Cochrane Databases were searched using the keywords "delirium" and "antipsychotics." References of review articles were reviewed to identify additional studies. Study selection criteria included prospective design, more than 10 participants (in treatment arms), mean age 60 and older, standardized criteria for diagnosing delirium, and validated delirium rating scales for reporting outcomes. RESULTS: Thirteen articles met selection criteria: six single-agent and seven comparison studies. Of these, eight (62%) had fewer than 25 participants in treatment arms, 10 (77%) recruited participants from psychiatry referrals, and eight (62%) did not clearly describe their screening methods. All single-agent studies were open-label studies. Of the comparison studies, five (71%) used randomization, but only one of these (a placebo-controlled study) used adequate allocation concealment methods, and only one other study (comparing two antipsychotics) described a double-blind method in detail. In the only placebo-controlled study (which was stopped early), no statistically significant differences in mean delirium severity scores were found at individual time points (Days 2, 3, 4, 7, 10). The other 12 studies reported improvements in delirium severity or resolution of delirium based on cutoff scores of the scales, but it is not clear from any of these studies what the natural course of delirium would have been without use of antipsychotics. CONCLUSION: Because of severe methodological limitations, the studies in this review do not support the use of antipsychotics in the treatment of delirium in older hospitalized adults. Additional well-designed randomized placebo-controlled trials are needed.

Intestinal dipeptide absorption is preserved during thermal injury and cytokine treatment.

BACKGROUND: Intestinal barrier function is impaired during thermal injury; however, the effects of thermal injury on the absorption of dietary peptides are not well characterized. The purpose of this study was to determine the impact of thermal injury on dipeptide absorption in rats and to describe the influence of inflammatory cytokines on the expression of the oligopeptide transporter PEPT1 and dipeptide permeability in cultured intestinal cells (Caco-2 cells). METHODS: Sprague Dawley rats were assigned to 30% body surface area burn (n = 7) or sham (n = 8) groups. Twenty-four hours following burn/sham, the proximal jejunum was cannulated. The jejunal segment was perfused with buffer containing the dipeptide glycylsarcosine (Gly-Sar), and intestinal permeability (P(eff)) was calculated. For in vitro experiments, Caco-2 cells were grown on permeable supports and treated with tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10 (10 ng/mL) alone and in combination for 48 hours. The effective apical-to-basolateral permeabilities (P(eff)) of Gly-Sar were measured, and PEPT1 expression was determined using reverse transcription-polymerase chain reaction. RESULTS: Gly-Sar P(eff) was similar in burn and sham rats (6.67 +/- 2.27 x 10(-5) vs 7.58 +/- 2.20 x 10(-5) cm/s, respectively, P = .45). In Caco-2 cells, cytokine treatment did not alter PEPT1 expression (P = .954) or the P(eff) of Gly-Sar (P = .806). CONCLUSIONS: Intestinal absorption of the dipeptide Gly-Sar is preserved 24 hours following thermal injury in rats. Likewise, PEPT1 expression and peptide absorption are preserved following treatment with TNF-alpha, IL-6, and IL-10 in Caco-2 monolayers. These findings imply that intestinal dipeptide absorption may be preserved during burn injury. This may lead to new strategies to optimize enteral protein delivery in burn patients.