Comparison of Fixed Dosing vs Train of Four Titration of Cisatracurium in COVID-19 ARDS Patients.

Background: Early neuromuscular blockade with cisatracurium has been associated with improved outcomes in moderate-severe acute respiratory distress syndrome (ARDS). Previous studies have demonstrated increased drug utilization without benefits in oxygenation using fixed dose cisatracurium compared to train-of-four (TOF) titration. Objective: We sought to compare a novel, lower fixed dose cisatracurium protocol to TOF titration evaluating the impact on PaO2:FiO2 ratio (P/F). Methods: We conducted a single-center retrospective cohort study comparing fixed dose cisatracurium to TOF titration. We included patients aged 18-89 treated for COVID-19 ARDS with a baseline P/F≤200 who received a cisatracurium infusion for ≥12 h. The primary outcome was change in P/F at 48 h from baseline. Secondary outcomes included change in P/F at 24 h and 7 days, need for mechanical ventilation at day 28, and cisatracurium utilization. Results: Analyses included 125 patients (fixed dose = 65, TOF = 60). Severe ARDS was common with a baseline median P/F of 73.7 vs 79.5, P = .133. The change in P/F at 48 h was larger in the TOF cohort in the adjusted analysis (24.9 vs 70.8, P < .005). The rate and total cumulative dose of cisatracurium were higher in the fixed dose cohort (5 vs 3 mcg/kg/min, P < .001; 1034 vs 612 mg, P < .001) despite similar infusion durations (44.1 h vs 48.5 h, P = .642). Conclusions: Patients in the TOF cisatracurium cohort had improved P/F at 48 h compared to the fixed dose cohort, while also using only 60% of the cumulative dose. Future directions should include analysis of the implications of increased cisatracurium exposure on patient outcomes.

A Resident-Preceptor Collaboration to Encourage Wellness and Reduce Burnout Amongst Pharmacy Residents.

Pharmacy residents are especially vulnerable to burnout given the professional and personal stressors associated with postgraduate training. Residency programs need to prioritize burnout reduction strategies to support resident health and well-being. This commentary describes a resident-preceptor collaborative approach to encourage wellness and reduce burnout within a large residency program at an academic medical center. Strategies that have been utilized include (1) fostering collaboration among residents and preceptors; (2) assessing resident interests and needs to ensure alignment; (3) leveraging available institutional and community resources; and (4) integrating initiatives within the existing residency program structure. This commentary aims to provide suggestions that can be implemented to address resident burnout for other residency programs, regardless of resource availability.

Impact of initial fluid resuscitation volume on clinical outcomes in patients with heart failure and septic shock.

Background: Fluid resuscitation is a key treatment for sepsis, but limited data exists in patients with existing heart failure (HF) and septic shock. The objective of this study was to determine the impact of initial fluid resuscitation volume on outcomes in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with septic shock. Methods: This multicenter, retrospective, cohort study included patients with known HF (LVEF ≤50%) presenting with septic shock. Patients were divided into two groups based on the volume of fluid resuscitation in the first 6 h; <30 mL/kg or ≥30 mL/kg. The primary outcome was a composite of in-hospital mortality or renal replacement therapy (RRT) within 7 days. Secondary outcomes included acute kidney injury (AKI), initiation of mechanical ventilation, and length of stay (LOS). All related data were collected and compared between the two groups. A generalized logistic mixed model was used to assess the association between fluid groups and the primary outcome while adjusting for baseline LVEF, Acute Physiology and Chronic Health Evaluation (APACHE) II score, inappropriate empiric antibiotics, and receipt of corticosteroids. Results: One hundred and fifty-four patients were included (93 patients in <30 mL/kg group and 61 patients in ≥30 mL/kg group). The median weight-based volume in the first 6 h was 17.7 (12.2-23.0) mL/kg in the <30 mL/kg group vs. 40.5 (34.2-53.1) mL/kg in the ≥30 mL/kg group (P <0.01). No statistical difference was detected in the composite of in-hospital mortality or RRT between the <30 mL/kg group compared to the ≥30 mL/kg group (55.9% vs. 45.9%, P=0.25), respectively. The <30 mL/kg group had a higher incidence of AKI, mechanical ventilation, and longer hospital LOS. Conclusions: In patients with known reduced or mildly reduced LVEF presenting with septic shock, no difference was detected for in-hospital mortality or RRT in patients who received ≥30 mL/kg of resuscitation fluid compared to less fluid, although this study was underpowered to detect a difference. Importantly, ≥30 mL/kg fluid did not result in a higher need for mechanical ventilation.

Efficacy of Continuous Infusion Ketamine for Analgosedation in the Medical Intensive Care Unit: A Propensity-Weighted Analysis.

BACKGROUND: Few randomized controlled trials have evaluated the use of ketamine vs opiate-based analgosedation. METHODS: A retrospective cohort analysis of 169 mechanically ventilated patients admitted to the medical intensive care unit (MICU) at an academic medical center was conducted to evaluate efficacy of ketamine vs opiate-based analgosedation by comparing the percentage of time within target sedation range. The primary outcome was percentage of time within target sedation range (RASS -1 to +1) within first 72 hours of primary sedation initiation. Secondary outcomes including percentage of time under-sedated, over-sedated, and in coma; use of concomitant analgesic, sedative, and antipsychotic agents; presence of delirium; percentage of CPOT scores at goal; and hemodynamic effects were also evaluated. RESULTS: After weighting, the mean percentage of time at RASS goal for ketamine patients was 43.0% compared to 41.4% for opiate-based sedation patients. Ketamine was not significantly non-inferior to opiate-based sedation for the mean percentage of time at RASS goal (P = .11). The median percentage of CPOT scores at goal was 13.3% higher in the ketamine group (P = .042). Patients in the ketamine group received significantly less additional sedative agents than the patients in the opiate-based sedation group. CONCLUSION: A similar percent of time at RASS goal was found for the ketamine analgosedation group compared to the opiate-based sedation group, although this did not reach statistical signicance for non-inferiority due to lack of statistical power. This study found a higher percentage of CPOT scores within goal with less additional sedative agents required compared to an opiate-based sedation regimen.

Characterization of Medication Discrepancies and Interventions Resulting From Pharmacy-Led Medication Reconciliation in the Critical Care Setting.

BACKGROUND: Medication reconciliation has been shown to reduce medication-related errors in hospitalized patients, but the impact of pharmacy-led medication reconciliation in the intensive care unit (ICU) has not been extensively studied. METHODS: This was a retrospective chart review of patients with a pharmacy-led medication reconciliation on admission to an ICU between January 1st and March 31st, 2018. Pharmacy-led medication reconciliations were completed by pharmacists, pharmacy residents, and pharmacy students. The objective of this study was to describe medication discrepancies identified by pharmacy-led medication reconciliation and to evaluate the interventions following. RESULTS: A total of 288 patients were screened and 247 met inclusion criteria. There were 1148 medication discrepancies identified resulting in an average of 4.65 discrepancies per patient. Medication addition (54.25%) and medication deletion (45.75%) were most common. Within 24 hours of medication reconciliation, 214 interventions were made to active orders. No differences were observed between discrepancies identified and type of pharmacy staff completing the medication reconciliation. CONCLUSIONS: This study identified a high rate of medication discrepancies on admission to the ICU. Furthermore, it describes the types of pharmacist interventions following pharmacy-led medication reconciliation. This process may be impactful to incorporate as a standard practice in ICUs and warrants further investigation into value, cost, and pharmacist workflow.

National opioid shortage is associated with increased use of ketamine infusion for analgosedation in the medical intensive care unit.

OBJECTIVE: To assess the impact of the national shortage of injectable opioids during the winter of 2017-2018 on the use of ketamine infusion for analgosedation in the medical intensive care unit (MICU). DESIGN: A retrospective cohort study. SETTING: Single-center tertiary care MICU at The Ohio State University Wexner Medical Center. PATIENTS: All patients who received continuous infusion of ketamine to facilitate mechanical ventilation between May 1, 2015 and September 1, 2018. MEASUREMENTS AND MAIN RESULTS: Seventy-seven patients were identified during the study time frame: 43 before and 19 during the opioid shortage. During the peak of the shortage, there was a sevenfold increase in orders for ketamine infusion (2.2 patients/week vs 0.32 patients/week; p < 0.001). Median time from the start of mechanical ventilation to initiation of ketamine infusion was significantly shorter during the shortage (14.1 hours) versus before (51.2 hours; p = 0.03). There was a trend toward adding ketamine into the sedation regimen earlier during the shortage (mean number of drips added prior to ketamine was 2.74 during the shortage vs 3.3 before; p = 0.06). There was also a trend toward increased use of ketamine infusion as monotherapy during (21.1 percent of patients) versus before the shortage (7 percent), though this did not reach statistical significance (p = 0.19). CONCLUSION: The national opioid shortage may have led to earlier and more frequent use of ketamine infusion for anaglosedation in mechanically ventilated MICU patients.

EARLY INITIATION OF VASOPRESSIN REDUCES ORGAN FAILURE AND MORTALITY IN SEPTIC SHOCK.

ABSTRACT: Purpose : The aim of the study is to determine whether initiating vasopressin earlier in septic shock reduces organ dysfunction and in-hospital all-cause mortality. Methods : This multicenter, retrospective, cohort study evaluated patients admitted to the medical intensive care unit between October 2011 and August 2018 with septic shock who received vasopressin within 48 hours of shock onset. The primary composite outcome was the proportion of patients with a change in the Sequential Organ Failure Assessment score greater than 3 from baseline to 72 hours after initiation of vasopressin and/or in-hospital all-cause mortality. Secondary outcomes included time to hemodynamic stability, acute kidney injury, and intensive care unit length of stay. Results : A total of 385 patients included in the final evaluation with a mean Acute Physiology and Chronic Health Evaluation II score of 31 and a mean baseline Sequential Organ Failure Assessment score of 13. Median time to initiation of vasopressin after norepinephrine was 7.3 hours. The primary composite outcome was significantly reduced in patients who had vasopressin initiated earlier in septic shock (odds ratio = 1.08, 95% confidence interval = 1.03-1.13, P < 0.001). After controlling for baseline data in a multivariable regression model the primary outcome remained statistically significant (odds ratio = 1.04, 95% confidence interval = 1.02-1.07, P = 0.001). Conclusions : Early initiation of vasopressin in septic shock may reduce the risk of in-hospital all-cause mortality and/or organ dysfunction.

Risk Factors Associated with Suboptimal Tobramycin Levels in the Medical Intensive Care Unit.

BACKGROUND: Optimal aminoglycoside dosing in critically ill patients represents a challenge for practitioners, especially in the medical intensive care unit (MICU). MICU patients exhibit altered pharmacokinetics due to pathophysiological changes the body undergoes in critical illness, leading to possible treatment failure. The literature surrounding optimal dosing and therapeutic drug monitoring strategies of aminoglycosides in MICU patients is scarce and conflicting. Additionally, only a few studies have investigated risk factors for suboptimal pharmacokinetic target obtainment. Currently, no definitive risk factors have been identified to predict suboptimal aminoglycoside target obtainment in MICU patients. OBJECTIVE: The objective of this study was to determine risk factors for suboptimal pharmacokinetic target obtainment in patients receiving tobramycin in the MICU. METHODS: This single-center, retrospective cohort study included patients 18-89 years old who received at least one 7 mg/kg tobramycin dose in the MICU from January, 1 2015 to September, 30 2020. Patients also had to have at least two detectable drug levels obtained at least one half-life apart following the first tobramycin dose. The primary outcome was to determine the incidence of optimal pharmacokinetic target obtainment, defined as a tobramycin maximum concentration (Cmax) ≥ 10 mcg/ml, and to identify the risk factors for suboptimal (Cmax < 10 mcg/mL) pharmacokinetic target obtainment, in MICU patients. Secondary outcomes were compared between suboptimal and optimal target obtainment in patients with culture confirmed gram-negative infection susceptible to tobramycin. These secondary outcomes included all-cause in-hospital mortality, ICU length of stay (LOS), hospital LOS, and vasopressor duration in those with shock. RESULTS: A total of 230 patients were included in this retrospective study. For the primary outcome, 187 (81.3%) patients achieved optimal target obtainment. Through multivariate logistic regression, female sex and serum albumin < 2.5 g/dL were identified as independent risk factors for suboptimal target obtainment; [OR = 2.14; 95% CI (1.05-4.37), p = 0.037], [OR = 2.50; 95% CI (1.21-5.19), p = 0.014], respectively. Fifty-four (23%) patients had culture-confirmed gram-negative infections susceptible to tobramycin and were included in the subgroup analysis. Of these 54 patients, 11 (20.4%) did not achieve optimal target concentrations. In patients with culture-confirmed gram-negative infection, there was no difference between patients with optimal target obtainment and suboptimal target obtainment in ICU LOS, hospital LOS, all-cause mortality, or vasopressor duration in those with shock. CONCLUSIONS: Among patients receiving their first dose of tobramycin in the MICU, 81.3% obtained an optimal serum concentration. Female sex and serum albumin < 2.5 g/dL were identified as risk factors for suboptimal target obtainment; however, further research is warranted to assess the utility of using these two covariates as risk factors for more aggressive dosing in critically ill MICU patients.

Implementation of a Protocol for Peripheral Intravenous Norepinephrine: Does It Save Central Line Insertion, Is It Safe?

BACKGROUND: Central venous catheters (CVC) are generally recommended for norepinephrine administration due to risk of tissue ischemia. Early resuscitation, leading to decreased infusion duration, may minimize the need for CVCs if norepinephrine can be administered safely through a peripheral intravenous catheter (PIV). OBJECTIVE: A protocol was developed for peripheral administration. Safety, CVC placement, and adherence with protocol elements were evaluated. METHODS: A single-center, prospective, observational pilot was conducted for patients receiving norepinephrine in the Medical Intensive Care Unit (MICU). Patients were considered for PIV administration of low dose norepinephrine for less than 24 hours based on clinical status and anticipated short-term use. Protocolized interventions for PIV's included criteria for gauge, number, and site as well as visual inspection and evaluation every 2 hours. Data was collected on protocol elements to evaluate safety and effectiveness of the protocol. RESULTS: There were 316 occurrences of norepinephrine infusions including 92 via PIV (patients may have received multiple treatments). 34% (31/92) did not require a CVC. 3 had infiltrated PIV's without tissue injury. Maximum dose adherence was 73%. 97% of infusions ran less than 24 hours. Nursing adherence included: 91% gauge, 65% proper site, 99% adequate number, 49% blood return on initiation, 55% ongoing blood return, and 61% IV site checked. CONCLUSION: Our results suggest that norepinephrine is safe to administer through a PIV at low doses for less than 24 hours using a protocol. Prevention of unnecessary CVC insertion is beneficial by minimizing the risk of central line complications thus improving patient morbidity.

Acutely ill hematology/oncology patients with central-line associated bloodstream infections and the impact of timing of catheter removal on outcomes.

BACKGROUND: Hematology/oncology patients are at risk for central line-associated bloodstream infections (CLABSI). The purpose was to determine if infection-related mortality, persistent bacteremia, and recurrent bacteremia were decreased with early central venous catheter (CVC) removal. METHODS: A case-matched, retrospective cohort study was conducted comparing patients with early catheter removal (≤12 hours) to late catheter removal (>12 hours) in hematology/oncology patients with CLABSI from June 1, 2015 to May 31, 2018. Patients were case-matched based on intensive care unit admission and presence of shock to control for severity of illness. RESULTS/DISCUSSION: Of 148 patients meeting study inclusion, 128 (86.5%), had their CVC removed during hospitalization (median 11.8 hours). The majority had a hematologic malignancy (90.5%). Following case-matching, 48 patients remained in each group. The primary outcome of infection-related mortality, persistent bacteremia, or recurrent bacteremia occurred more frequently in the late catheter removal group compared to the early catheter removal group although this was not statistically significant (18.8% vs 8.3%, P = .136). CONCLUSIONS: A lower incidence of infection-related mortality, persistent bacteremia, and recurrent bacteremia was found in patients early catheter removal; however the sample size was not adequate to detect statistical differences. Investigators should continue to evaluate if early catheter removal confers a benefit in a larger patient population.

Early onset delirium incidence and risk factors in hematology oncology patients admitted to the intensive care unit: A retrospective cohort study.

Background: Delirium occurs frequently in intensive care unit (ICU) patients; however, there are limited data evaluating its impact on critically ill hematology-oncology patients. We aimed to determine the incidence and risk factors for early-onset delirium development in hematology-oncology patients admitted to the ICU. Methods: This single-center, retrospective cohort study evaluated the primary outcome of incident delirium within 7 days of ICU admission in adults admitted to the hematology-oncology medical or surgical ICU. Patients with delirium (DEL) were compared to those without (No-DEL) for evaluation of secondary endpoints including hospital mortality, ICU, and hospital length of stay (LOS). Multivariable logistic regression modeling was performed to identify independent risk factors for delirium. Results: Delirium occurred in 125 (51.2%) of 244 patients. Inhospital mortality was significantly higher in the DEL vs. No-DEL group (32.8% vs. 15.1%, P = 0.002). Median (1st and 3rd quartiles) ICU and hospital LOS were significantly longer in the delirium group, respectively (6 [4-10] days vs. 3 [2-5] days, P < 0.001, and 21 [14-36] days vs. 12 [8-22] days, P < 0.001). Higher Sequential Organ Failure Assessment score, high-dose corticosteroids, mechanical ventilation (MV), and brain metastases were each independently, associated with an increased delirium risk. Conclusion: Hematology-oncology patients admitted to the ICU frequently develop delirium. Consistent with literature in nonhematology-oncology critically ill patients, identified independent risk factors for delirium were MV and organ dysfunction. Risk factors unique to the critically ill hematology-oncology patient population include high-dose corticosteroids and brain metastases. Further research is needed to evaluate strategies to mitigate delirium development in this population based on risk assessment.

Comparison of Lurasidone Versus Quetiapine for the Treatment of Delirium in Critically Ill Patients.

OBJECTIVE: To evaluate the efficacy and safety of lurasidone compared with quetiapine for treatment of delirium in critically ill patients. DESIGN: Prospective, observational cohort study. SETTING: Single-center community teaching hospital. PATIENTS: Forty adult intensive care unit (ICU) patients with delirium (Confusion Assessment Method in the ICU positive), tolerating enteral nutrition, and without active alcohol withdrawal or prior use of atypical antipsychotics. INTERVENTIONS: Patients were treated at the discretion of the prescriber with either lurasidone or quetiapine for delirium. Dose escalation and/or discontinuation were determined at the discretion of individual providers. RESULTS: Baseline characteristics differed with a higher severity of illness in patients in the quetiapine group (n = 20) and a higher baseline QTc interval in the lurasidone group (n = 20). No significant difference was seen in the time to delirium resolution (3.2 vs 3.4 days), average daily haloperidol requirements (5.7 vs 6.9 mg), hospital length of stay (LOS; 23.6 vs 27.9 days), or ICU LOS (12.1 vs 14.2 days). Lurasidone was associated with fewer ventilator support days (4.0 [interquartile range, IQR: 2.3-6.8] days vs 7 [IQR: 4.0-9.8; P = .0295] days) but also a fewer number of delirium-free days (0 [IQR: 0-1.0] days vs 2 [IQR: 0-3.0; P = .0231] days). Additionally, no difference was seen for ICU mortality (20% vs 20%), percentage of time oversedated (2.8% vs 2.7%), or incidence of QTc prolongation (10.0% vs 10.0%). CONCLUSIONS: Lurasidone for the treatment of delirium in critically ill patients did not differ in the time to delirium resolution when compared to quetiapine. Additionally, the incidence of QTc prolongation between agents does not appear to be different. Future randomized trials should evaluate dose escalation schemes and a larger proportion of patients to evaluate differences in mortality, efficacy, and life-threatening arrhythmias associated with atypical antipsychotic use.

Clinical outcomes following treatment of Enterobacter species pneumonia with piperacillin/tazobactam compared to cefepime or ertapenem.

BACKGROUND: Enterobacter spp. are a common cause of nosocomial pneumonia and treatment can be complicated by AmpC resistance. Carbapenems are the treatment of choice; however, alternatives are needed. Cefepime has been shown to be non-inferior to carbapenems. There are limited data to support the use of piperacillin/tazobactam. The objective of this study was to determine if piperacillin/tazobactam is non-inferior to cefepime or ertapenem for Enterobacter pneumonia treatment. OBJECTIVES: To compare the rate of clinical cure in patients with Enterobacter pneumonia receiving definitive treatment with piperacillin/tazobactam, cefepime, or ertapenem. Secondary outcomes included hospital mortality, infection-related length of stay, duration of mechanical ventilation, recurrent pneumonia, and resistance. METHODS: Retrospective, single-center study. RESULTS: Of 114 patients included, 59 received definitive treatment with piperacillin/tazobactam and 55 received cefepime or ertapenem. There was no difference in the proportion of patients who achieved clinical cure in the piperacillin/tazobactam group compared to the cefepime or ertapenem group (76.3% vs. 87.3%, P = 0.13). Treatment group was not associated with clinical cure when controlling for confounders in multivariable logistic regression (adjusted odds ratio [OR] 0.59, 95% confidence interval [CI] 0.15-2.37). The rate of recurrent pneumonia was 11.4% in the piperacillin/tazobactam group and 6.7% in the cefepime or ertapenem group (P = 0.48). Other secondary outcomes did not differ between the groups. CONCLUSIONS: In this retrospective study of patients with Enterobacter pneumonia, clinical cure with piperacillin/tazobactam was comparable to that with cefepime or ertapenem; however, a prospective trial with a larger population is needed to determine if definitive treatment with piperacillin/tazobactam is non-inferior to definitive treatment with cefepime or ertapenem.

Evaluating off-label uses of acetazolamide.

PURPOSE: Current off-label uses of acetazolamide in hospitalized patients are reviewed. SUMMARY: Acetazolamide is a carbonic anhydrase inhibitor typically used for indications including epilepsy, glaucoma, edema, and altitude sickness but it may be prescribed in hospitalized patients for off-label indications. It inhibits carbonic anhydrase, which leads to reduced hydrogen ion secretion in the proximal renal tubule, resulting in increased bicarbonate and cation excretion and causing urinary alkalization and diuresis. In addition, acetazolamide decreases the production of cerebrospinal fluid (CSF) and aqueous humor, reducing intracranial pressure (ICP) and intraocular pressure. This allows acetazolamide to be used for treatment of idiopathic intracranial hypertension and elevated ICP due to CSF leaks to avoid invasive procedures. It is a sulfonamide derivative, with dosages ranging from 250 to 4,000 mg daily divided every 6-12 hours. The plasma half-life is 4-8 hours, though the pharmacologic effects of acetazolamide last longer. Acetazolamide is highly protein bound and primarily eliminated by the kidneys, so administration should not be more frequent than every 12 hours if creatinine clearance is less than 50 mL/min. Limited literature exists describing the optimal patients to receive acetazolamide therapy. CONCLUSION: The potential benefits of acetazolamide include ventilator weaning for chronic obstructive pulmonary disease patients, avoidance of invasive procedures in patients with a CSF leak or elevated ICP, and prevention of high-dose methotrexate toxicity and contrast-induced nephropathy. Uncertainty remains regarding the selection of patients who would best benefit from acetazolamide use.

Thromboembolic complications following aminocaproic acid use in patients with hematologic malignancies.

Aminocaproic acid is frequently used in patients with hematologic malignancy that present with thrombocytopenia with or without hemorrhage. We conducted a retrospective study to evaluate the safety of aminocaproic acid in 109 patients with hematologic malignancies. Patients were included if aminocaproic acid had been administered for at least 24 hours for the prevention or treatment of thrombocytopenic hemorrhage. Our primary outcome was thromboembolic complications defined as arterial or venous thrombotic events objectively confirmed by imaging studies. Thromboembolic complications occurred in five patients (4.6%) and all were venous thromboses. Other than the underlying malignancy, these patients also had many concurrent risk factors including indwelling central venous catheters, which could have contributed to thromboses. In conclusion, in our population of patients with a variety of hematological malignancies, aminocaproic acid does not appear to be associated with a high incidence of thromboembolic complications.

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.

INTRODUCTION: Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. METHODS: A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. RESULTS: Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. CONCLUSION: The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

Methadone analgesia in the critically ill.

PURPOSE: Methadone is increasingly used as an analgesic or a bridge to weaning other analgesics and sedatives in critically ill patients. This review discusses the pharmacology of methadone, summarizes available evidence for its use in the intensive care unit setting, and makes suggestions for appropriate use and monitoring. MATERIALS/METHODS: Articles evaluating the efficacy, safety, and pharmacology of methadone were identified from a PubMed search through June 2015. References from selected articles were reviewed for additional material. Experimental and observational English-language studies that focused on the efficacy, safety, and pharmacology of methadone in critically-ill adults and children were selected. RESULTS: Methadone is a synthetic opioid analgesic with potential advantages over other commonly used opioids. Limited evidence from critically ill pediatric, adult, and burn populations suggests that methadone protocols may expedite weaning opiate infusions, decrease the length of mechanical ventilation, and reduce the incidence of negative outcomes such as opiate withdrawal, delirium, and over-sedation. CONCLUSIONS: Data from current literature supports a role for methadone analgesia in weaning opiates and potentially reducing the duration of mechanical ventilation in critically ill patients. More studies are needed to confirm these benefits and determine criteria for patient selection.