Bruce Doepker

A comparison of severe hemodynamic disturbances between dexmedetomidine and propofol for sedation in neurocritical care patients

Objective:Dexmedetomidine and propofol are commonly used sedatives in neurocritical care as they allow for frequent neurologic examinations. However, both agents are associated with significant hemodynamic side effects. The primary objective of this study is to compare the prevalence of severe hemodynamic effects in neurocritical care patients receiving dexmedetomidine and propofol. Design:Multicenter, retrospective, propensity-matched cohort study. Setting:Neurocritical care units at two academic medical centers with dedicated neurocritical care teams and board-certified neurointensivists. Patients:Neurocritical care patients admitted between July 2009 and September 2012 were evaluated and then matched 1:1 based on propensity scoring of baseline characteristics. Interventions:Continuous sedation with dexmedetomidine or propofol. Measurements and Main Results:A total of 342 patients (105 dexmedetomidine and 237 propofol) were included in the analysis, with 190 matched (95 in each group) by propensity score. The primary outcome of this study was a composite of severe hypotension (mean arterial pressure < 60 mm Hg) and bradycardia (heart rate < 50 beats/min) during sedative infusion. No difference in the primary composite outcome in both the unmatched (30% vs 30%, p = 0.94) or matched cohorts (28% vs 34%, p = 0.35) could be found. When analyzed separately, no differences could be found in the prevalence of severe hypotension or bradycardia in either the unmatched or matched cohorts. Conclusions:Severe hypotension and bradycardia occur at similar prevalence in neurocritical care patients who receive dexmedetomidine or propofol. Providers should similarly consider the likelihood of hypotension or bradycardia before starting either sedative.

Effects of etomidate on vasopressor use in patients with sepsis or severe sepsis: A propensity-matched analysis☆ , ☆☆

PURPOSE The safety of single-bolus etomidate to facilitate intubation in septic patients is controversial due to its potential to suppress adrenal steroidogenesis. The purpose of this study was to evaluate the effects of etomidate on the development of shock when used as an induction agent to facilitate intubation in septic patients. METHODS A multicenter, retrospective, propensity-matched cohort study comparing patients with sepsis or severe sepsis who either received etomidate or did not receive etomidate for intubation was conducted. The primary outcome was the difference in the need for vasopressor support within 72 hours after intubation. Secondary outcomes included the use of multiple vasopressors, intensive care unit length of stay, and in-hospital mortality. RESULTS A total of 411 patients were analyzed. Eighty-three patients were matched by propensity score. There was no difference in the matched cohort in regards to vasopressor use within 72 hours of intubation (odds ratio, 0.95; 95% confidence interval, 0.52-1.76; P=.88). Furthermore, there were no significant differences observed with regard to secondary outcomes, including in-hospital mortality (P=.76). CONCLUSIONS The use of etomidate for intubation in septic patients did not increase vasopressor requirements within 72 hours after intubation.

Thromboembolic Events During Continuous Vasopressin Infusions: A Retrospective Evaluation

Background: Published guidelines suggest that vasopressin has a role in shock treatment, although its safety has not been adequately evaluated in a clinical setting. Vasopressin causes platelet aggregation and has been associated with the release of factor VIII coagulant and von Willebrand factor. Objective: To compare the incidence of venous thromboembolism (VTE) in patients with a diagnosis of shock who received vasopressin with those who did not receive vasopressin for hemodynamic support. Methods: A retrospective, single-center, cohort study was conducted at an academic, tertiary care center with 350 patients with a diagnosis of shock. Patients from the intensive care unit were randomly selected and separated into 2 groups for comparison of those receiving only catecholamines with those receiving vasopressin with or without catecholamines for hypotension. Patients with diabetes insipidus or variceal hemorrhage and those with any documented history of VTE were excluded. The primary outcome, VTE occurrence, was defined as a positive Doppler ultrasound, spiral computed tomography, or documented diagnosis in the discharge records. Frequency and type of risk factors for VTE were compared between the 2 study arms. A risk factor modeling approach was performed, using logistic regression to identify potential confounders and effect modifiers in the relationship between vasopressin and VTE. Results: There were 175 patients in each arm of the study. The crude incidence of VTE was 7.4% and 8% in the vasopressin and catecholamine groups, respectively (p = 0.84). No significant difference in the incidence of deep venous thrombosis (vasopressin 5.1%, control 7.4%; p = 0.51) or pulmonary embolism (vasopressin 2.3%, control 0.6%; p = 0.37) was found between groups. After adjusting for covariates, there was no statistically significant difference in the incidence of VTE between the 2 arms (p = 0.72). Conclusions: This investigation provides initial evidence that vasopressin infusions do not increase the risk of VTE in patients with shock.

Association between chloride content of intravenous fluids and acute kidney injury in critically ill medical patients with sepsis

HighlightsHigh‐chloride fluids may be associated with increased risk of acute kidney injury and mortality.The incidence of acute kidney injury was higher in patients who received high‐chloride fluids.After multivariable logistic regression was applied primary outcome remained significant.

938: PHENOBARBITAL COMPARED TO USUAL CARE FOR FIRST-LINE TREATMENT OF SEVERE ALCOHOL WITHDRAWAL SYNDROME

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: Acute enteral and intrathecal baclofen withdrawal can be life threatening if not managed appropriately. Symptoms of acute baclofen withdrawal include insomnia, confusion, delirium, hallucinations, hyperthermia, agitation, seizures, spasticity, dyskinesia, and muscle rigidity. Methods: A 61 year old male with a past medical history significant for chronic back pain and spinal stenosis was admitted to the medical intensive care unit with confusion, insomnia, agitation, delirium, and auditory and visual hallucinations. He was on baclofen as an outpatient and his last dose was 9 days prior to admission. He had been experiencing worsening symptoms for 7 days preceding presentation. Vital signs were normal. On physical exam his pupils were dilated, but equal and reactive to light. His speech was tangential and incomprehensible. Serum toxicology was negative. Urine toxicology was positive for benzodiazepine, tetrahydrocannabinol, and tricyclic antidepressants. The patient was taking diazepam and disclosed smoking marijuana prior to admission. Creatine phosphokinase was elevated at 683 U/L. All other laboratory results and imaging were normal. To control his agitation he received 10mg of intravenous (IV) haloperidol, 1mg of IV lorazepam, and 14mg of IV midazolam with minimal improvement; therefore dexmedetomidine was initiated which led to significant clinical improvement. Upon further investigation it was determined that the patient was taking approximately 10 baclofen 20mg tablets a day. According to his pharmacy records he filled 738 baclofen tablets in the previous 12 weeks. His presentation and sudden discontinuation of high dose baclofen led to a diagnosis of baclofen withdrawal. Baclofen was subsequently restarted and dexmedetomidine was weaned off in 36 hours. Results: Treatment of baclofen withdrawal includes supportive care and re-initiating baclofen. Agents utilized for acute agitation including benzodiazepines provide little relief to this patient population. Dexmedetomidine provided significant improvement in this patient’s agitation, delirium, and mental status without suppressing his respiratory drive. There are limited pharmacotherapeutic interventions available to manage symptoms of baclofen withdrawal. There has been only one case report published in the literature that addresses utilization of dexmedetomidine for intrathecal baclofen withdrawal. Dexmedetomidine should be considered for acute enteral baclofen withdrawal.

Review of Continuous Infusion Neuromuscular Blocking Agents in the Adult Intensive Care Unit

The use of continuous infusion neuromuscular blocking agents remains controversial. The clinical benefit of these medications may be overshadowed by concerns of propagating intensive care unit–acquired weakness, which may prolong mechanical ventilation and impair the inability to assess neurologic function or pain. Despite these risks, the use of neuromuscular blocking agents in the intensive care unit is indicated in numerous clinical situations. Understanding pharmacologic nuances and clinical roles of these agents will aid in facilitating safe use in a variety of acute disease processes. This article provides clinicians with information regarding pharmacologic differences, indication for use, adverse effects, recommended doses, ancillary care, and monitoring among agents used for continuous neuromuscular blockade.

601: PROPENSITY MATCHED ANALYSIS COMPARING HYPOTENSION BETWEEN ETOMIDATE AND KETAMINE IN SEPTIC PATIENTS

Learning Objectives: Etomidate is commonly used for intubation with minimal hemodynamic effects, however its suppression of cortisol production may have a significant impact on a patient’s ability to maintain hemodynamic stability. Ketamine is also frequently used and has minimal effects on hemodynamics but no proven influence on the adrenal axis. Methods: A retrospective cohort study was performed to compare the incidence of clinical hypotension between ketamine and etomidate in critically ill septic patients. Clinical hypotension was defined as: mean arterial pressure (MAP) decrease > 40% and MAP <70 mmHg, MAP <60 mmHg, systolic blood pressure (SBP) 15 min, initiation of vasopressors, or increase to > 30% of the initial vasopressor dose. In addition, patients were evaluated for length of hospital and ICU stay, and mortality. Statistical analyses included unmatched and matched cohorts using a propensity score analysis. Multivariable logistic regression was used to evaluate the incidence of clinical hypotension 24 hr post intubation and vasopressor requirements. Results: A total of 260 patients were included for analysis (129 etomidate and 131 ketamine) with 138 patients matched 1:1 based on propensity score. Prior to propensity matching, clinical hypotension 24 hr post intubation was 75.2% in the etomidate group compared to 69.5% in the ketamine group (p=0.302) and there was no statistical difference in new post intubation shock (37.2%; 48.5%, p=0.067). After matching no statistical difference was found in clinical hypotension within 24 hr (40.6%; 40.6%, p=0.99). A random-effects logistic regression model was applied and there was a 38% reduction in clinical hypotension with ketamine (OR=0.62; 95% CI 0.3–1.29, p=0.2). There was also no statistical difference in ICU or hospital length of stay or mortality. Conclusions: Administration of etomidate for intubation did not increase the incidence of clinical hypotension 24 hr post intubation when compared to ketamine in septic patients. Large, prospective trials are warranted to confirm these results.

Using Health Care Failure Mode and Effects Analysis for High-Risk Medications:

The Directors Forum series is edited by Robert Weber and Scott Mark and is designed to guide pharmacy leaders in establishing patient-centered services in hospitals and health systems. This months article focuses on a health care failure mode and effects analysis (HC-FMEA) to analyze the prescribing of high-risk medications. HC-FMEA can provide the pharmacy director with a powerful approach to directly changing processes to improve medication safety.

PANCURONIUM: NEUROMUSCULAR BLOCKING AGENT OF CHOICE FOR THE CRITICALLY ILL?: 604

Introduction: According to the “SCCM Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient,” pancuronium (P) can be used appropriately in the majority of ICU patients. Hypothesis: P is not the appropriate Neuromuscular Blocking Agent (NMBA) in the majority of ICU patients in our university, tertiary care center. Methods: A pharmacist review of continuous infusion NMBAs was performed to determine the appropriateness and frequency of each agent being used in the MICU, SICU, CCU, and BMT. MUE guidelines dictated agent selection based on the presence of renal insufficiency (UO<25ml/hr x 8hrs or CrCl<50ml/min), liver dysfunction (2x ULN AST, ALT, ALP, or bili), high dose steroids (1-1.5mg/kg/day of prednisone equivalents), or cardiac risk (HR>100bpm or arrhythmogenic risk). Recommended agents were vecuronium (V), cis-atracurium (C), and P. Results: 34 patients (mean age 50yrs) were evaluated between Aug 2003 and Feb 2004. All patients received continuous infusion benzodiazepine±opioid or propofol or had a documented Ramsay score >3 prior to paralysis. Mean APACHE II score on admission was 33. 38% of patients had renal insufficiency, 24% had liver dysfunction, 18% received high dose steroids, and 82% had a baseline HR >100bpm. Patients received C, V, and P 56, 41, and 3% of the time, respectively. C was the appropriate agent in 53% and V was appropriate in 47% of patients. P was not appropriate for use in any patient. The mean baseline HR in our patient sample was 113bpm. P was commonly not chosen in this patient population because of the high incidence of cardiac disease in our ICU population and the arrhythmogenic potential of the medication. Conclusions: Critically ill patients frequently have cardiac disease and are predisposed to cardiac arrhythmias. Although P is recommended for the majority of patients in the SCCM guidelines, it was not an appropriate choice in our patient population due to the incidence of vagolysis and increased heart rate with this agent. A review of the SCCM Clinical Practice Guidelines is recommended.