Road Map for Research Training in the Residency Learning Experience.

The American Society of Health-System Pharmacists residency accreditation standards require all postgraduate residency training programs to teach and evaluate a resident's ability to advance practice through project development and presentation, underscoring the importance of conducting research in today's professional climate. Although many residents express strong interest in research participation and contributing to the medical literature, many obstacles to publication have been identified. We aim to illustrate a deliberate approach to teaching this material and structuring the longitudinal experience in a way that maximizes resources to overcome these barriers. Such efforts should aid residents, advisors, and program directors in establishing curriculum which leads to successful completion and publication of pharmacy resident's research projects.

Evaluating Muscle Mass by Using Markers of Kidney Function: Development of the Sarcopenia Index.

OBJECTIVES: Sarcopenia is associated with a poor prognosis in the ICU. The purpose of this study was to describe a simple sarcopenia index using routinely available renal biomarkers and evaluate its association with muscle mass and patient outcomes. DESIGN: A retrospective cohort study. SETTING: A tertiary-care medical center. PATIENTS: High-risk adult ICU patients from October 2008 to December 2010. INTERVENTIONS: The gold standard for muscle mass was quantified with the paraspinal muscle surface area at the L4 vertebrae in the subset of individuals with an abdominal CT scan. Using Pearson's correlation coefficient, serum creatinine-to-serum cystatin C ratio was found to be the best performer in the estimation of muscle mass. The relationship between sarcopenia index and hospital and 90-day mortality, and the length of mechanical ventilation was evaluated. MEASUREMENTS AND MAIN RESULTS: Out of 226 enrolled patients, 123 (54%) were female, and 198 (87%) were white. Median (interquartile range) age, body mass index, and body surface area were 68 (57-77) years, 28 (24-34) kg/m, and 1.9 (1.7-2.2) m, respectively. The mean (± SD) Acute Physiology and Chronic Health Evaluation III was 70 (± 22). ICU, hospital, and 90-day mortality rates were 5%, 12%, and 20%, respectively. The correlation (r) between sarcopenia index and muscle mass was 0.62 and coefficient of determination (r) was 0.27 (p < 0.0001). After adjustment for Acute Physiology and Chronic Health Evaluation III, body surface area, and age, sarcopenia index was independently predictive of both hospital (p = 0.001) and 90-day mortality (p < 0.0001). Among the 131 patients on mechanical ventilator, the duration of mechanical ventilation was significantly lower on those with higher sarcopenia index (-1 d for each 10 unit of sarcopenia index [95% CI, -1.4 to -0.2; p = 0.006]). CONCLUSIONS: The sarcopenia index is a fair measure for muscle mass estimation among ICU patients and can modestly predict hospital and 90-day mortality among patients who do not have acute kidney injury at the time of measurement.

Perceived safety and efficacy of neuromuscular blockers for acute respiratory distress syndrome among medical intensive care unit practitioners: A multicenter survey.

PURPOSE: Neuromuscular blocking agents (NMBAs) are frequently used in patients with acute respiratory distress syndrome (ARDS). The purpose of this survey is to describe providers' knowledge and perceived efficacy and safety of NMBAs in patients with ARDS. MATERIALS AND METHODS: We performed a prospective, multicenter survey of medical intensive care unit intensivists, fellows, nurse practitioners (NPs), physician's assistants (PAs), and pharmacists at 5 tertiary care centers between July 2012 and May 2013. RESULTS: A total of 335 surveys were sent to providers, with a 47% response rate. Ninety-eight percent of providers correctly identified that NMBAs lack anxiolytic and analgesic properties. The effect of end-organ damage on NMBA clearance was less commonly identified by NPs/PAs for both hepatic (P=.0077) and renal (P=.0272) dysfunction compared with physicians. More NP/PAs identified the association of consciousness with the use of NMBAs than physicians (P=.047). Forty-two percent of prescribers reported always or frequently using continuous-infusion NMBAs in patients with severe ARDS, with 89% initiating NMBAs because of ventilator dyssynchrony. Prescribers perceived continuous NMBAs to be more effective than inhaled prostaglandins (74% vs 56%) in severe ARDS but less safe (45% vs 84%). Train of 4 was identified by 54% of prescribers as their primary method for titration. CONCLUSION: Providers are knowledgeable about NMBAs, but educational opportunities exist. Perceptions about the efficacy and safety of NMBAs varied among prescribers, and inconsistencies existed in the prioritization of management strategies for ARDS.

Drug Class Combination-Associated Acute Kidney Injury.

OBJECTIVE: To evaluate the quality of available evidence of drug class combinations and their association with the development of acute kidney injury (AKI). DATA SOURCES: A search of MEDLINE and Embase databases was completed using the following terms: "risk factor AND (acute kidney injury or acute kidney failure) AND (drug or medication)." STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria were the following: English language, full-text availability, and at least 1 drug-combination. Each citation was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. The literature was evaluated using the quality of evidence component of GRADE. No standardized definition of AKI was applied throughout.. DATA SYNTHESIS: Out of 2139 total citations, 151 were assessed for full-text review, with 121 citations (6%) meeting inclusion criteria, producing76 unique drug class combinations. Overall, 56 combinations (73.7%) were considered very low quality; 12 (15.8%) were considered low quality. There were 8 (10.5%) of moderate quality, and no combination was considered high quality. 58 (76%) combinations that had a single citation,with a mean of 1.6 citations per drug class combination. The combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics was reported in 10 citations, the largest number of citations. CONCLUSIONS: Our study demonstrates a lack of well-designed studies addressing drug class combination-associated AKI. The combination of NSAIDs and diuretics with or without additional renin-angiotensin aldosterone agents had the strongest level of evidence. Despite limitations, the information included in this review may result in additional scrutiny about combining certain individual nephrotoxic drugs.

Cystatin C Falsely Underestimated GFR in a Critically Ill Patient with a New Diagnosis of AIDS.

Cystatin C has been suggested to be a more accurate glomerular filtration rate (GFR) surrogate than creatinine in patients with acquired immunodeficiency syndrome (AIDS) because it is unaffected by skeletal muscle mass and dietary influences. However, little is known about the utility of this marker for monitoring medications in the critically ill. We describe the case of a 64-year-old female with opportunistic infections associated with a new diagnosis of AIDS. During her course, she experienced neurologic, cardiac, and respiratory failure; yet her renal function remained preserved as indicated by an eGFR ≥ 120 mL/min and a urine output > 1 mL/kg/hr without diuresis. The patient was treated with nephrotoxic agents; therefore cystatin C was assessed to determine if cachexia was resulting in a falsely low serum creatinine. Cystatin C measured 1.50 mg/L which corresponded to an eGFR of 36 mL/min. Given the >60 mL/min discrepancy, serial 8-hour urine samples were collected and a GFR > 120 mL/min was confirmed. It is unclear why cystatin C was falsely elevated, but we hypothesize that it relates to the proinflammatory state with AIDS, opportunistic infections, and corticosteroids. More research is needed before routine use of cystatin C in this setting can be recommended.

Levetiracetam Pharmacokinetics During Continuous Venovenous Hemofiltration and Acute Liver Dysfunction.

BACKGROUND: Levetiracetam clearance is dependent on renal (major) and hepatic (minor) elimination pathways. In the setting of organ dysfunction, dose reductions are recommended to prevent accumulation. Continuous venovenous hemofiltration (CVVH) has been shown to eliminate levetiracetam, but the preferred dosing regimen when a patient is on CVVH and has concomitant acute liver dysfunction is unknown. The objective of this case is to describe levetiracetam dosing and pharmacokinetics in the setting of CVVH and acute liver dysfunction. METHODS: This is a case report of a single patient. RESULTS: A 59-year-old male was admitted to the intensive care unit for acute onset multiorgan dysfunction associated with a hematologic disorder. His hospital course was complicated by persistent liver dysfunction with a model for end-stage liver disease score of 47 and renal failure which necessitated initiation of CVVH. On hospital day two, the patient developed new-onset focal seizures secondary to metabolic abnormalities that resulted in the initiation of levetiracetam 1000 mg intravenously twice daily. The peak concentration at steady state was 32.2 mcg/mL, and the trough concentration was 16.1 mcg/mL (goal 12-46 mcg/mL). The volume of distribution was 0.65 L/kg, and the elimination half-life was 11.4 h. CONCLUSION: Levetiracetam pharmacokinetics observed in this case approximated those seen in a normal healthy patient and a regimen of 1000 mg twice daily achieved serum trough concentrations at the lower limit of the target range. This case indicates that in a patient with acute liver dysfunction on CVVH, 1000 mg twice daily may be considered as an empiric levetiracetam regimen.

Risk Factors for Dexmedetomidine-Associated Hemodynamic Instability in Noncardiac Intensive Care Unit Patients.

BACKGROUND: The reported incidence of hypotension and bradycardia in patients receiving dexmedetomidine for sedation commonly exceeds 50%. In this study, we describe the incidence of, patient- and treatment-specific risk factors for, and clinical significance of dexmedetomidine-associated hemodynamic instability. METHODS: This retrospective cohort study was conducted in critically ill adults receiving dexmedetomidine for sedation at Mayo Clinic Hospital in Rochester, MN, during a 1-year period. The primary end point was hemodynamic instability: a composite of hypotension and/or bradycardia, defined as systolic blood pressure <80 mm Hg, diastolic blood pressure <50 mm Hg, or heart rate <50 beats per minute during dexmedetomidine therapy. Cox proportional hazards models were constructed to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk factors of hemodynamic instability. RESULTS: Hemodynamic instability occurred in 197 of the analyzed 300 patients receiving dexmedetomidine, resulting in a cumulative incidence of 71% at 24 hours via Kaplan-Meier estimation. In addition to dexmedetomidine, univariate analysis identified age, vasopressor use, low baseline arterial blood pressure, and concomitant sedatives as associated with increased risk of hemodynamic instability. Multivariable analysis demonstrated associations between age (HR, 1.23 per 10 years, 95% CI, 1.10-1.38) and low baseline blood pressure (HR, 2.42 at dexmedetomidine initiation, 95% CI, 1.68-3.49) and risk of hemodynamic instability. Variables such as concomitantly administered cardiac medications or sedative therapies and dexmedetomidine infusion rates >0.7 µg/kg/h were not found to be predictors of hemodynamic instability among the analyzed sample. CONCLUSIONS: Hemodynamic instability commonly occurs in critically ill adults receiving dexmedetomidine, with more than two thirds of this cohort experiencing hypotension and/or bradycardia within 24 hours of initiation. Increasing age and low baseline arterial blood pressure were associated with the development of hemodynamic instability. These findings suggest that clinicians should be aware of the potential risk of hemodynamic instability when using dexmedetomidine in patients with advanced age or low baseline arterial blood pressure.

Overestimation of Glomerular Filtration Rate Among Critically Ill Adults With Hospital-Acquired Oligoanuric Acute Kidney Injury.

BACKGROUND: Medication use in the intensive care unit (ICU) depends on creatinine-based glomerular filtration rate (GFR) estimates. Urine output deterioration may precede the creatinine rise resulting in delayed recognition of GFR reductions. Our objective was to quantify the disparity between estimated GFR (eGFR) and true GFR in ICU patients with hospital-acquired oligoanuric acute kidney injury (hAKI). METHODS: This single-center cohort study examined adults who met the Acute Kidney Injury Network stage III urine output criterion ≥48 hours after ICU admission. True GFR was ≤15 mL/min/1.73 m(2), and eGFR was described by 6 different creatinine-based equations. True GFR and eGFR were compared on the day of hAKI diagnosis and followed for 4 days using multivariable linear regression with generalized estimating equations, adjusting for day and method. RESULTS: Of the 691 patients screened, we enrolled 61 patients. After adjustment for multiple comparisons and day, there were significant differences in eGFR between the estimation methods and true GFR (P < .001). After day adjustment, eGFR overestimated true GFR by 17 to 50 mL/min/1.73 m(2) and overestimation persisted through the fourth day of hAKI (P ≤ .001). CONCLUSION: Creatinine-based equations overestimated GFR in ICU patients with hAKI. This study highlights a population at risk of medication misadventures in whom systems optimization should be considered.

Key Controversies in Colloid and Crystalloid Fluid Utilization.

Nearly 2 centuries have passed since the use of intravenous fluid became a foundational component of clinical practice. Despite a steady stream of published investigations on the topic, questions surrounding the choice, dose, timing, targets, and cost-effectiveness of various fluid options remain insufficiently answered. In recent years, 2 of the most debated topics reference the role of albumin in acute care and the safety of normal saline. Although albumin has a place in therapy for specific patient populations, its high cost relative to other fluids makes it a less desirable option for hospitals and health systems with escalating formulary scrutiny. Pharmacists bear responsibility for reconciling this disparity and supporting the rational use of albumin in acute care through a careful evaluation of recently published literature. In parallel, it has become clear that crystalloids should no longer be considered a homogenous class of fluids. The past reliance on normal saline has been questioned due to recent findings of renal dysfunction attributable to the solution's supraphysiologic chloride concentration. These safety concerns with 0.9% sodium chloride may result in a practice shift toward more routine use of "balanced crystalloids," such as lactated Ringer's or Plasma-Lyte, that mimic the composition of extracellular fluid. The purpose of this review is to summarize the evidence regarding these 2 important fluid controversies that are likely to affect hospital pharmacists in the coming decades - the evidence-based use of human albumin and the rising role of balanced salt solutions in clinical practice.

Intensive Care Nurses' Knowledge About Use of Neuromuscular Blocking Agents in Patients With Respiratory Failure.

BACKGROUND: The recent increase in use of neuromuscular blocking agents (NMBAs) in patients with acute respiratory distress syndrome is set against a backdrop of concerns about harm associated with use of these high-risk drugs. Bedside nurses play a pivotal role in the safe and effective use of these agents. OBJECTIVE: To describe critical care nurses' knowledge of the therapeutic properties, adverse effects, and monitoring parameters associated with NMBAs. METHODS: A prospective, multicenter survey of medical intensive care unit nurses between July 2012 and May 2013. The web-based survey instrument was designed, pretested, and administered under the direction of a multidisciplinary group of individuals. RESULTS: Responses from 160 nurses (22% of eligible nurses) were analyzed. Most respondents were able to identify NMBAs correctly as nonanalgesic (93%) and nonanxiolytic (83%). The perceived durations of action of NMBAs varied widely, and few nurses were familiar with patient-specific considerations related to drug elimination. Most (70%) recognized the independent associations between NMBAs and footdrop, muscle breakdown, and corneal ulceration. Pressure ulcers and a history of neuromuscular disease were the characteristics of patients perceived to most heighten the risk of NMBA use. CONCLUSIONS: Critical care nurses are knowledgeable about the importance of concurrent analgesia and sedation during use of NMBAs. Routes of elimination, duration of action, and adverse effects were less commonly known and represent areas for focused education and quality improvement surrounding use of NMBAs in the intensive care unit.

Levetiracetam Pharmacokinetics in a Patient Receiving Continuous Venovenous Hemofiltration and Venoarterial Extracorporeal Membrane Oxygenation.

Levetiracetam is a first-line therapy for seizures in critically ill patients because of its clinical efficacy, minimal drug interactions, and wide therapeutic window. The primary mechanism of levetiracetam clearance is renal, and the drug has a low molecular weight. It is hydrophilic and exhibits minimal protein binding. Thus it is expected that levetiracetam will be removed by continuous venovenous hemofiltration (CVVH), with limited clearance by venoarterial extracorporeal membrane oxygenation (ECMO). We describe the case of a 67-year-old man who was admitted to the cardiovascular surgery intensive care unit after cardiac arrest and initiation of venoarterial ECMO. His course was complicated by multiorgan dysfunction including acute renal failure requiring CVVH. On hospital day 6, intravenous levetiracetam, at a loading dose of 2000 mg followed by a maintenance dose of 1000 mg every 12 hours, was initiated for new-onset seizures. The volume of distribution was 0.65 L/kg, and clearance was measured with peak (ranging from 26.5-39.8 µg/ml) and trough (ranging from 13.9-18.2 µg/ml) concentrations. Elimination half-life ranged from 8.7-10.1 hours. Renal dysfunction reduces levetiracetam clearance, and dosage reductions are recommended to prevent accumulation. Current CVVH dosing recommendations are based on predicted removal without clinical data. The volume of distribution and clearance in this case were similar to those of a normal healthy patient. Based on these results, we recommend considering an initial levetiracetam dose of 1000 mg every 12 hours for patients receiving CVVH, with dosage adjustments based on therapeutic drug monitoring.

Extracorporeal Elimination of Piperacillin/Tazobactam during Molecular Adsorbent Recirculating System Therapy.

Use of the Molecular Adsorbent Recirculating System (MARS) as a liver support device continues to grow worldwide. Various components of the MARS circuit remove both protein-bound and water-soluble molecules. Little is known about the extent of the enhanced clearance mechanisms used in MARS therapy on drug elimination. Of particular interest to acute care practitioners is the impact of MARS on antibiotic clearance, as suboptimal concentrations of such drugs can negatively impact patient outcomes. The properties of piperacillin/tazobactam suggest that elimination may be enhanced in the setting of MARS therapy. We describe two cases in which this was studied. Piperacillin concentrations were determined at various points within the MARS circuit, and patient serum concentrations were reported throughout the dosing interval while receiving MARS therapy. Piperacillin concentrations in both cases were in excess of the desired goal minimum inhibitory concentrations for treatment of gram-negative infections. Use of an extended-infusion strategy of piperacillin/tazobactam 3.375 or 4.5 g given every 8 hours maintained desired serum levels throughout the dosing interval. To our knowledge, this is the second published report on the use of piperacillin/tazobactam during MARS therapy. These case reports reveal successful dosing strategies for patients requiring piperacillin/tazobactam while receiving MARS therapy, as well as quantify the influence of individual MARS elements on drug extraction.

Relationship Between Triglyceride Tolerance, Body Mass Index, and Fat Depots in Hospitalized Patients Receiving Parenteral Nutrition.

BACKGROUND: Hypertriglyceridemia has been associated with adverse outcomes in patients receiving intravenous fat emulsions (IVFEs), but little is known about its prevalence and causes. MATERIALS AND METHODS: The study investigated whether a relationship exists between body mass index (BMI) and triglyceride tolerance in parenterally fed patients. We conducted a retrospective analysis of 287 adults receiving parenteral nutrition to determine whether patients with very low BMI (VLBMI, <16 kg/m(2)) tolerate IVFEs better than do patients with low BMI (LBMI, 16-18.4 kg/m(2)), normal-weight patients (NBMI, 18.5-24.9 kg/m(2)), and overweight/obese patients (HBMI, ≥25 kg/m(2)). RESULTS: The median triglyceride concentration during IVFE was significantly lower in VLBMI patients at 107 mg/dL compared with 124 mg/dL in non-VLBMI patients (P = .016), despite higher lipid infusion rates in the VLBMI group. There was a significant association between triglycerides and BMI in the aggregate cohort (R = 0.2375, P < .0001), with the highest frequency of hypertriglyceridemia occurring in HBMI patients despite relatively lower lipid and energy supply. In a subset of VLBMI patients (n = 36) who had an abdominal computed tomography scan, there was 25- to 100-fold variability in the size of the abdominal adipose tissue depots. In this subgroup, triglyceride concentrations correlated with visceral fat but not subcutaneous abdominal fat. CONCLUSIONS: In summary, patients with VLBMI have lower triglyceride concentrations during IVFEs than do other individuals, but there is considerable variability in triglycerides and body fat in this group. Caution should be employed with the use of IVFEs, especially in HBMI patients.

Paliperidone Palmitate Associated with Necrotizing Deep Tissue Infection and Sepsis Requiring Surgical Intervention.

Long-acting injectable antipsychotics provide the delivery of medication over an extended period of time requiring administration typically only every 2 to 4 weeks. The side effect profile of a long-acting injectable antipsychotic is predictable and similar to the oral formulation. However, injection site reactions may occur with this novel delivery system. The risk of an injection site reaction may be greater with the repeated administration of a lipophilic decanoate formulation and include pain, development of indurations, and fibrosis. Severe complications from injection site reactions have rarely been described in the literature with newer agents. We report the first case of a patient prescribed paliperidone palmitate every 3 weeks that developed severe sepsis requiring vasopressors and intubation due to delayed relayed recognition of a necrotizing infection at an injection site. Clinicians should be alerted to screen for injection site reactions when there is an unknown source infection in a patient receiving a long-acting injectable antipsychotic.

Circulatory Support with Venoarterial ECMO Unsuccessful in Aiding Endogenous Diltiazem Clearance after Overdose.

Introduction. In cardiovascular collapse from diltiazem poisoning, extracorporeal membrane oxygenation (ECMO) may offer circulatory support sufficient to preserve endogenous hepatic drug clearance. Little is known about patient outcomes and diltiazem toxicokinetics in this setting. Case Report. A 36-year-old woman with a history of myocardial bridging syndrome presented with chest pain for which she self-medicated with 2.4 g of sustained release diltiazem over the course of 8 hours. Hemodynamics and mentation were satisfactory on presentation, but precipitously deteriorated after ICU transfer. She was given fluids, calcium, vasopressors, glucagon, high-dose insulin, and lipid emulsion. Due to circulatory collapse and multiorgan failure including ischemic hepatopathy, she underwent transvenous pacing and emergent initiation of venoarterial ECMO. The peak diltiazem level was 13150 ng/mL (normal 100-200 ng/mL) and it remained elevated at 6340 ng/mL at hour 90. Unfortunately, the patient developed multiple complications which resulted in her death on ICU day 9. Conclusion. This case describes the unsuccessful use of ECMO for diltiazem intoxication. Although past reports suggest that support with ECMO may facilitate endogenous diltiazem clearance, it may be dependent on preserved hepatic function at the time of cannulation, a factor not present in this case.

Serum cystatin C predicts vancomycin trough levels better than serum creatinine in hospitalized patients: a cohort study.

INTRODUCTION: Serum cystatin C can improve glomerular filtration rate (GFR) estimation over creatinine alone, but whether this translates into clinically relevant improvements in drug dosing is unclear. METHODS: This prospective cohort study enrolled adults receiving scheduled intravenous vancomycin while hospitalized at the Mayo Clinic in 2012. Vancomycin dosing was based on weight, serum creatinine with the Cockcroft-Gault equation, and clinical judgment. Cystatin C was later assayed from the stored serum used for the creatinine-based dosing. Vancomycin trough prediction models were developed by using factors available at therapy initiation. Residuals from each model were used to predict the proportion of patients who would have achieved the target trough with the model compared with that observed with usual care. RESULTS: Of 173 patients enrolled, only 35 (20%) had a trough vancomycin level within their target range (10 to 15 mg/L or 15 to 20 mg/L). Cystatin C-inclusive models better predicted vancomycin troughs than models based upon serum creatinine alone, although both were an improvement over usual care. The optimal model used estimated GFR by the Chronic Kidney Disease Epidemiology Collaborative (CKD-EPI) creatinine-cystatin C equation (R(2) = 0.580). This model is expected to yield 54% (95% confidence interval 45% to 61%) target trough attainment (P <0.001 compared with the 20% with usual care). CONCLUSIONS: Vancomycin dosing based on standard care with Cockcroft-Gault creatinine clearance yielded poor trough achievement. The developed dosing model with estimated GFR from CKD-EPIcreatinine-cystatin C could yield a 2.5-fold increase in target trough achievement compared with current clinical practice. Although this study is promising, prospective validation of this or similar cystatin C-inclusive dosing models is warranted.

Derivation of urine output thresholds that identify a very high risk of AKI in patients with septic shock.

BACKGROUND AND OBJECTIVES: To promote early detection of AKI, recently proposed pretest probability models combine sub-Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria with baseline AKI risk. The primary objective of this study was to determine sub-KDIGO thresholds that identify patients with septic shock at highest risk for AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective analysis of 390 adult patients admitted to the medical intensive care unit (ICU) of a tertiary, academic medical center with septic shock between January 2008 and December 2010. Hourly urine output was collected from the time of septic shock recognition (hour 0) to hour 96, urine catheter removal, or ICU discharge (whichever occurred first). All available serum creatinine (SCr) measurements were collected until hour 96. The AKI pretest probability model was assessed during the first 12 hours of resuscitation and included the initial episode of oliguria, increase from baseline to peak SCr level, and Acute Physiology and Chronic Health Evaluation (APACHE) III score in a multivariable receiver-operator characteristic (ROC) analysis. The primary outcome was the incidence of stage II or III (stage II+) AKI defined by KDIGO criteria. Secondary outcomes included the need for RRT and 28-day mortality. RESULTS: Ninety-eight (25%) patients developed stage II+ AKI after septic shock recognition. APACHE III score and increase in SCr level in the first 12 hours were not statistically associated with stage II+ AKI in multivariable ROC analysis. Consecutive oliguria for 3 hours had fair predictive ability for achieving stage II+ AKI criteria (area under ROC curve, 0.73; 95% confidence interval [95% CI], 0.68 to 0.78), and oliguria for 5 hours demonstrated optimal accuracy (82%; 95% CI, 79% to 86%). CONCLUSIONS: Three to 5 hours of consecutive oliguria in patients with septic shock may provide a valuable measure of AKI risk. Further validation to support this finding is needed.

Assessment of a modified 4T scoring system for heparin-induced thrombocytopenia in critically ill patients.

PURPOSE: The purpose of the study is to determine if a modified 4T (m4T) scoring system, which omits clinical evaluation of other thrombocytopenic etiologies, is different from the 4T scoring system's probability to predict a positive heparin-induced thrombocytopenia (HIT) laboratory test in the intensive care unit. MATERIALS AND METHODS: This is a single-centered retrospective analysis of critically ill adults who had an enzyme-linked immunosorbent assay antiplatelet factor 4 antibody (ELISA anti-PF4 Ab) ordered. Patients were identified as HIT positive (optical density, ≥0.40) or HIT negative (optical density, <0.40) based on the ELISA anti-PF4 Ab. Both 4T and m4T scores were calculated, and the diagnostic accuracy was compared using paired receiver operating characteristic curves. RESULTS: A total of 1487 adult intensive care unit patients with an ELISA anti-PF4 Ab ordered between January 2007 and December 2009 were eligible for study enrollment. Application of exclusion criteria and random selection yielded a total of 232 patients included for analysis (58 HIT-positive and 174 HIT-negative patients). The area under the curve for the 4T and m4T scores were 0.683 (95% confidence interval, 0.604-0.762) and 0.680 (95% confidence interval, 0.600-0.759), respectively (P=.065). CONCLUSION: This study does not show a difference in the probability of the m4T and 4T scoring systems to predict a positive ELISA anti-PF4 Ab test in the critically ill patient population. Further prospective studies are needed to validate the m4T scoring system.

Influence of dexmedetomidine therapy on the management of severe alcohol withdrawal syndrome in critically ill patients.

PURPOSE: Although benzodiazepines are first-line drugs for alcohol withdrawal syndrome (AWS), rapidly escalating doses may offer little additional benefit and increase complications. The purpose of this study was to evaluate dexmedetomidine's impact on benzodiazepine requirements and hemodynamics in AWS. MATERIALS AND METHODS: This retrospective case series evaluated 33 critically ill adults with a primary diagnosis of AWS from 2006 to 2012 at an academic medical center. RESULTS: Dexmedetomidine began a median (interquartile range) of 11 (2, 32) hours into intensive care unit admission and was titrated to an infusion rate of 0.7 (0.4, 0.7) µg kg(-1) h(-1) to achieve the desired depth of sedation. In the 12 hours after dexmedetomidine began, patients experienced a 20-mg reduction in median cumulative benzodiazepine dose used (P < .001), a 14-mm Hg lower mean arterial pressure (P = .03), and a 17-beats/min reduction in median heart rate (P < .001). Four (12%) patients experienced hypotension (systolic blood pressure <80 mm Hg) during therapy, and there were no cases of bradycardia (heart rate <40 beats/min). CONCLUSION: Dexmedetomidine decreased benzodiazepine requirements and improved the overall hemodynamic profile of patients with severe AWS. These results provide promising evidence about the potential benefit of dexmedetomidine for AWS.

Adjunctive aerosolized colistin for multi-drug resistant gram-negative pneumonia in the critically ill: a retrospective study.

BACKGROUND: The incidence of multi-drug resistant (MDR) gram-negative (GN) organisms including Pseudomonas and Acinetobacter spp has increased in the last decade, prompting re-evaluation of colistin for the management of these infections. Aerosolized colistin as an adjunct to intravenous therapy is a current option for the management of MDR-GN pneumonia, although data supporting this practice is limited. This study evaluates the efficacy of adjunctive aerosolized colistin in combination with intravenous colistin in critically ill patients with MDR-GN pneumonia. METHODS: A retrospective multi-center cohort analysis comparing critically ill patients with MDR-GN pneumonia who received intravenous colistin (IV) alone or in combination with adjunctive aerosolized colistin (IV/AER) with a primary endpoint of clinical cure at the end of colistin therapy. Secondary endpoints included microbiologic cure, duration of mechanical ventilation, length of stay, and hospital mortality. A post-hoc subgroup analysis was performed for patients with high quality cultures used for diagnosis of MDR-GN pneumonia. Dichotomous data were compared using Fisher's exact test while the student's t-test or Mann-Whitney U test were used for continuous variables. RESULTS: Ninety-five patients met criteria for evaluation with 51 patients receiving IV and 44 receiving IV/AER. Baseline characteristics were similar between the two groups. Twenty patients (39.2%) receiving IV and 24 (54.5%) receiving IV/AER achieved clinical cure (p = 0.135). There was no difference in microbiologic cure rates between the IV and IV/AER colistin groups (40.7vs. 44.4%, p = 0.805). The IV group demonstrated a trend towards higher pneumonia attributable mortality (70.4 vs. 40%, p = 0.055). In the subgroup analysis of patients with high quality respiratory cultures, there was a significantly lower clinical cure rate for those in the IV group as compared to the IV/AER group (31.3 vs. 57.1%, p = 0.033). CONCLUSIONS: Addition of aerosolized colistin to IV colistin may improve clinical cure and mortality for patients with MDR-GN pneumonia. Larger, prospective trials are warranted to confirm the benefit of adjunctive aerosolized colistin in critically ill patients with MDR-GN pneumonia.