Impact of early rasburicase on incidence of clinical tumor lysis syndrome in lymphoma.

Early administration of rasburicase to enhance uric acid (UA) elimination has been adopted without robust evidence in support of its impact on clinical outcomes in tumor lysis syndrome (TLS), specifically, the prevention of acute kidney injury (AKI). This was a retrospective cohort study of adult lymphoma patients at intermediate or high risk for TLS. Excluded patients had AKI or were on dialysis at hospital admission. The incidence of new AKI in the setting of TLS was described along with predictors of its development, including early rasburicase use. In 383 included patients, the incidence of new-onset AKI during hospitalization was 6%. Predictors included age, history of renal or cardiovascular disease, and UA >8 mg/dL. Rasburicase use did not significantly impact the risk of developing AKI (HR 2.3; p = .11). The UA level at the time of administration did not modify the effect of rasburicase on prevention of AKI (p = .36 for the interaction term).

Renal Recovery following Liposomal Amphotericin B-Induced Nephrotoxicity.

BACKGROUND: Acute kidney injury (AKI) is a common complication of treatment with liposomal amphotericin B (LAmB). The trajectory of renal recovery after LAmB-associated AKI has not been well described, nor has effect of LAmB dose on recovery of renal function been explored. OBJECTIVE: Characterize the pattern of renal recovery after incident AKI during LAmB and determine potential influencing factors. METHODS: This retrospective cohort study analyzed patients who developed a ≥50% increase in serum creatinine while on LAmB. Patients were followed up until complete renal recovery or death or for 30 days, whichever occurred first. The primary outcome was complete renal recovery, defined as serum creatinine convalescence to within 10% of the patient's pretreatment baseline. Multivariable modeling was used to identify independent predictors of renal recovery. RESULTS: Ninety-eight patients experienced nephrotoxicity during LAmB, 94% of which received doses <7 mg/kg/day. Fifty-one patients at least partially recovered renal function and, of these, 32 exhibited complete recovery after a mean 9.8 ± 7.8 days. No statistical relationship was found between LAmB dose at the time of AKI or cumulative exposure to LAmB and the likelihood of renal recovery. Concomitant nephrotoxins, age, and pretreatment renal function did not modify this effect in multivariable analysis. CONCLUSION AND RELEVANCE: Our data suggests that LAmB dose did not impact the likelihood of renal recovery. Additional investigation is needed to confirm these findings when aggressive dosing strategies are employe. Additional research is also warranted to further characterize the course of recovery after LAmB-associated nephrotoxicity and comprehensive spectrum of renal outcomes.

Incidence of Acute Kidney Injury Among Critically Ill Patients With Brief Empiric Use of Antipseudomonal ß-Lactams With Vancomycin.

BACKGROUND: Nephrotoxins contribute to 20%-40% of acute kidney injury (AKI) cases in the intensive care unit (ICU). The combination of piperacillin-tazobactam (PTZ) and vancomycin (VAN) has been identified as nephrotoxic, but existing studies focus on extended durations of therapy rather than the brief empiric courses often used in the ICU. The current study was performed to compare the risk of AKI with a short course of PTZ/VAN to with the risk associated with other antipseudomonal ß-lactam/VAN combinations. METHODS: The study included a retrospective cohort of 3299 ICU patients who received ≥24 but ≤72 hours of an antipseudomonal ß-lactam/VAN combination: PTZ/VAN, cefepime (CEF)/VAN, or meropenem (MER)/VAN. The risk of developing stage 2 or 3 AKI was compared between antibiotic groups with multivariable logistic regression adjusted for relevant confounders. We also compared the risk of persistent kidney dysfunction, dialysis dependence, or death at 60 days between groups. RESULTS: The overall incidence of stage 2 or 3 AKI was 9%. Brief exposure to PTZ/VAN did not confer a greater risk of stage 2 or 3 AKI after adjustment for relevant confounders (adjusted odds ratio [95% confidence interval] for PTZ/VAN vs CEF/VAN, 1.11 [.85-1.45]; PTZ/VAN vs MER/VAN, 1.04 [.71-1.42]). No significant differences were noted between groups at 60-day follow-up in the outcomes of persistent kidney dysfunction (P = .08), new dialysis dependence (P = .15), or death (P = .09). CONCLUSION: Short courses of PTZ/VAN were not associated with a greater risk of short- or 60-day adverse renal outcomes than other empiric broad-spectrum combinations.

Prevention of Clostridium difficile Infection in Critically Ill Adults.

The incidence and severity of Clostridium difficile infection (CDI) remain high across intensive care units in the United States despite national efforts to decrease this escalating health care burden. Most published literature and guidelines address treatment rather than prevention, yet this approach may be too downstream to limit morbidity and mortality from the disease and its complications. Mechanisms to prevent CDI successfully include reducing modifiable risk factors and minimizing horizontal transmission of C. difficile spores between patients and the health care environment. Because CDI prevention is characterized by a bundled approach, it is difficult to quantify the individual impact of any one element; however, a number of patient- and facility-level strategies can be considered for CDI prevention. Robust hygiene strategies, diagnostic and antimicrobial stewardship, and particular prophylaxis maneuvers such as continuation of oral vancomycin or fidaxomicin in the setting of systemic antibiotics have all demonstrated benefit. The preventive roles of deprescribing acid suppressants, routine use of probiotics, or early fecal microbiota transplantation remain unclear. The focus of this review is to summarize the evidence related to primary and secondary CDI prevention in critically ill adults and provide a concise implementation pathway for clinicians and policymakers.

Perceptions regarding vasopressin use and practices in septic shock, and cost containment strategies.

Background: Clinician preferences and practices regarding appropriate vasopressin use in light of its increased acquisition cost secondary to rebranding has not been evaluated or described since the most recent iteration of the Surviving Sepsis Campaign Guideline was published. Objective: To assess vasopressin cost containment initiatives and pharmacists' opinions regarding appropriate vasopressin use. Methods: A scenario-based survey was distributed to critical care and emergency medicine pharmacists. Responses were characterized using frequency and descriptive statistics. Categorical variables between those who implemented changes (Vasopressin Cost Consideration) and those who did not (Usual Care) were compared using chi-square or Fisher's exact tests. McNemar's test was used to compare responses in clinical scenarios between Vasopressin Cost Consideration and Usual Care groups. Results: Among 1757 pharmacists surveyed, 200 (11.3%) responded. When respondents considered vasopressin cost and evidence (vs evidence alone), fewer respondents would use vasopressin adjunctively with norepinephrine (21% vs 26.6%, P = 0.031), to raise mean arterial pressure compared with epinephrine (65.2% vs 72.3%, P = 0.012), or to reduce norepinephrine infusion rates (71.4% vs 81.4%, P < 0.001), but would use with steroids (62.4% vs 28.3%, P < 0.001). Most (72%) respondents had implemented vasopressin cost containment and/or education initiatives. The Vasopressin Cost Consideration group respondents were more likely to initiate vasopressin at 0.03 units/minute without titrating (47.9% vs 33.9%, P = 0.045). Conclusion: Since vasopressin was generically rebranded, most institutions have implemented at least one initiative to reduce vasopressin use and/or educate clinicians about its appropriate use. When vasopressin acquisition costs were considered, pharmacists recommended its use less frequently, particularly in clinical scenarios where its use is controversial.

Effects of clotrimazole troches on tacrolimus dosing in heart transplant recipients.

BACKGROUND: Tacrolimus is a cornerstone of immunosuppression after transplantation but is highly susceptible to changes from interacting variables and has a narrow therapeutic index. Clotrimazole troches are commonly used as a non-systemic antifungal to prevent oral candidiasis. Studies suggest that clotrimazole troches, though minimally absorbed systemically, may affect tacrolimus concentrations by inhibition of metabolic enzyme activity in the intestines. However, the magnitude of the impact of clotrimazole on tacrolimus dosing requirements to maintain goal levels is not well described. METHODS: To assess this, tacrolimus dose adjustments and trough concentrations were retrospectively examined in 95 heart transplant recipients before and after the discontinuation of clotrimazole. RESULTS: The median percent tacrolimus dose change was an increase of 66.7% (IQR 28.6%, 100%) after clotrimazole discontinuation, and the median trough concentration percent change from baseline to the first trough after clotrimazole discontinuation (in the absence of a dose change) was -42.5% (IQR -52.3%, -30.9%). Five cases of allograft rejection were observed. CONCLUSION: In conclusion, clotrimazole troches exert a meaningful interaction with tacrolimus that requires close monitoring and dose adjustment. The data from this single-center study provide novel information that could guide providers on the degree of tacrolimus dose adjustment needed when discontinuing clotrimazole prophylaxis after heart transplantation.

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.

Review of Infectious Disease Prophylaxis in Solid Organ Transplantation.

As immunosuppressive therapy has evolved over the years, rejection rates in solid organ transplant have declined, but infections remain a significant cause of morbidity and mortality in this population. Prophylaxis against bacterial, viral, and fungal infections is often used to prevent infection from common pathogens during high-risk periods. As an integral part of the multidisciplinary medical team, it is important that nurses caring for transplant recipients be familiar with methods to detect and prevent infectious diseases in this population. This article presents a review of risk factors for and prevalence of common infectious pathogens, as well as important considerations regarding prophylactic medications in solid organ transplant recipients.

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.

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.

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.

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.

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.

Predictors of mortality among bacteremic patients with septic shock receiving appropriate antimicrobial therapy.

BACKGROUND: Factors capable of impacting hospital mortality in patients with septic shock remain uncertain. Our objective was to identify predictors of hospital mortality among patients who received appropriate antimicrobial therapy for bacteremic septic shock after accounting for severity of illness, resuscitation status, and processes of care. METHODS: We conducted a secondary subgroup analysis of a prospective severe sepsis cohort study. Patients with septic shock and positive blood cultures who received appropriate antimicrobial therapy were included. Univariable analyses were used to identify differences between hospital survivors and non-survivors, and a multivariable logistic regression model revealed independent determinants of hospital mortality. RESULTS: From January 2008 to December 2010, 58 of 224 included patients died in the hospital. Multivariable logistic regression analysis demonstrated 2 independent predictors of hospital mortality. These included continuous renal replacement therapy utilization within 48 hours of septic shock recognition (adjusted odds ratio [OR], 5.52; 95% confidence interval [CI], 1.94-16.34) and intra-abdominal infection (adjusted OR, 3.92; 95% CI, 1.47-10.79). Escherichia coli was independently associated with a lower risk of hospital mortality (adjusted OR, 0.34; 95% CI, 0.11-0.90). CONCLUSION: Intra-abdominal infection and continuous renal replacement therapy were associated with increased hospital mortality in patients with septic shock who received appropriate antimicrobial therapy. Our findings may be explained by suboptimal intra-abdominal infection management or inadequate antimicrobial concentration in these patients.

Intravenous metoprolol versus diltiazem for rate control in noncardiac, nonthoracic postoperative atrial fibrillation.

BACKGROUND: Little guidance exists on effective management of postoperative atrial fibrillation (POAF) following noncardiac, nonthoracic (NCNT) surgery. OBJECTIVES: The purpose of this study was to identify whether a difference exists between intravenous (IV) metoprolol and diltiazem when used to achieve hemodynamically stable rate control in POAF following NCNT surgery. METHODS: This retrospective cohort study examined critically ill adult surgical patients experiencing POAF with rapid ventricular response. Inclusion in the metoprolol or diltiazem treatment group was determined by the initial rate control agent chosen by the prescriber. The primary end point was hemodynamically stable rate control, defined by heart rate (HR) <110 beats/min and blood pressure >90 mm Hg, maintained for 6 hours. MAIN RESULTS: Patients on metoprolol (n = 66) and diltiazem (n = 55) were similar in age, comorbidities, surgical procedure distribution, acuity of illness, and home rate and rhythm control medications continued during hospitalization; 76% of diltiazem-treated patients achieved hemodynamically stable rate control, compared with only 53% of those receiving metoprolol (P = .005). Safety end points were similar between groups, including the portion requiring a new vasopressor or fluid bolus for hemodynamic support. CONCLUSIONS: In NCNT surgery, patients with POAF, IV diltiazem more effectively controlled HR and hemodynamics compared with metoprolol. Results warrant further research into optimal medical management of POAF in this population using these 2 agents.

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.

Predictors of prolonged vasopressin infusion for the treatment of septic shock.

PURPOSE: Prolonged catecholamine use has been linked with poor clinical outcomes, including higher mortality. The objective was to identify characteristics that may be predictive of prolonged arginine vasopressin (AVP) use for 7 days or more in patients with septic shock. MATERIALS AND METHODS: This was a retrospective nested cohort analysis of adult patients receiving AVP as initial hemodynamic support for septic shock, either alone or in combination with norepinephrine, between 2008 and 2010. RESULTS: Univariate factors predictive of patients requiring extended AVP support were peripheral vascular disease (PVD) (48% vs 18%, P = .001), congestive heart failure (30% vs 12%, P = .024), and acute kidney injury (AKI) (83% vs 49%, P = .003). Patients requiring extended AVP support more frequently experienced a new intensive care unit (ICU) arrhythmia, typically atrial fibrillation (39% vs 7%, P < .001), and had higher 28-day mortality (74% vs 20%, P < .001). Multivariate analysis revealed that the strongest independent predictors of prolonged AVP dependence were new ICU arrhythmia (odds ratio [OR], 5.3; 95% confidence interval [CI], 1.6-17.8), PVD (OR, 4.3; 95% CI, 1.4-13.1), and AKI (OR, 3.9; 95% CI, 1.1-14.5). CONCLUSIONS: Patients with preexisting PVD and AKI and those experiencing a new ICU arrhythmia on AVP may be more likely to remain on AVP for 7 or more days.