Heather Personett

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 dexmedetomidines 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.

Clostridium difficile infection: a multicenter study of epidemiology and outcomes in mechanically ventilated patients.

Objectives:Clostridium difficile is a leading cause of hospital-associated infection in the United States. The purpose of this study is to assess the prevalence of C. difficile infection among mechanically ventilated patients within the ICUs of three academic hospitals and secondarily describe the influence of C. difficile infection on the outcomes of these patients. Design:A retrospective cohort study. Setting:ICUs at three teaching hospitals: Barnes-Jewish Hospital, Mayo Clinic, and Creighton University Medical Center over a 2-year period. Patients:All hospitalized patients requiring mechanical ventilation for greater than 48 hours within an ICU were eligible for inclusion. Interventions:None. Measurements and Main Results:A total of 5,852 consecutive patients admitted to the ICU were included. Three hundred eighty-six (6.6%) patients with development of C. difficile infection while in the hospital (5.39 cases/1,000 patient days). Septic shock complicating C. difficile infection occurred in 34.7% of patients. Compared with patients without C. difficile infection (n = 5,466), patients with C. difficile infection had a similar hospital mortality rate (25.1% vs 26.3%, p = 0.638). Patients with C. difficile infection were significantly more likely to be discharged to a skilled nursing or rehabilitation facility (42.4% vs 31.9%, p < 0.001), and the median hospital (23 d vs 15 d, p < 0.001) and ICU length of stay (12 d vs 8 d, p < 0.001) were found to be significantly longer in patients with C. difficile infection. Conclusions:Clostridium difficile infection is a relatively common nosocomial infection in mechanically ventilated patients and is associated with prolonged length of hospital and ICU stay, and increased need for skilled nursing care or rehabilitation following hospital discharge.

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

BackgroundThe 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.MethodsA 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.ResultsNinety-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).ConclusionsAddition 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.

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 &mgr;g/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.

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 systems 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.

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 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.

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 m2, 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 m2 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.

Impact of molecular adsorbent recirculating system therapy on tacrolimus elimination: a case report.

BACKGROUND We report a unique case which quantifies the effect of molecular adsorbent recirculating system (MARS [Gambro, Sweden]) therapy on blood concentrations of tacrolimus in a patient treated for refractory pruritus associated with recurrent hepatitis C of the liver allograft. Tacrolimus is a low-molecular-weight, highly protein-bound drug with the potential to be removed during MARS therapy. CASE REPORT Results of therapeutic drug monitoring revealed extracorporeal tacrolimus elimination accounted for only 0.3% of total drug removal during the session. CONCLUSIONS Although no explanation can be offered as to why MARS contributed so little to overall tacrolimus elimination, the data clearly show minimal impact of MARS on tacrolimus blood level.

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.