Anthony T. Gerlach

Dexmedetomidine: An Updated Review

Objective: To review recent literature on the safety and efficacy of dexmedetomidine. Data Sources: Articles were identified through searches of MEDLINE (1966–January 2007). Key words included dexmedetomidine, medetomidine, α2-agonist, and sedation. References from selected articles were reviewed for additional references. Study Selection and Data Extraction: Experimental and observational studies that focused on the safety and efficacy of dexmedetomidine in humans were selected. Data Synthesis: Dexmedetomidine is an α2-agonist for short-term sedation in critically ill patients. In postoperative patients, dexmedetomidine produced similar levels of sedation and times to extubation, with less opioid requirements compared with propofol. Dexmedetomidine has also been studied for sedation in critically ill medical and pediatric patients, as adjunct to anesthesia, and for procedural sedation. Hypotension, hypertension, and bradycardia are common adverse effects. Although dexmedetomidine is labeled only for sedation less than 24 hours, it has been administered for longer than 24 hours without apparent development of rebound hypertension and tachycardia. Conclusions: Dexmedetomidine is a safe and effective agent for sedation in critically ill patients. Further, well designed studies are needed to define its role as a sedative for critically ill medical, neurosurgical, and pediatric patients, as an adjunct to anesthesia, and as a sedative during procedures.

Enoxaparin and Bleeding Complications: A Review in Patients with and without Renal Insufficiency

Study Objective. To compare the frequency of bleeding complications from enoxaparin in patients with normal renal function versus patients with renal insufficiency.

An Updated Focused Review of Dexmedetomidine in Adults

Objective: To evaluate recent comparative studies regarding the safety and efficacy of dexmedetomidine in adults. Data Sources: Articles evaluating safety and efficacy of dexmedetomidine were identified from an English-language MEDLINE search (1996–July 2009), with a focus on data published since our previous review in 2007 to the present. MeSH terms included dexmedetomidine, medetomidine, α2:-agonist, and sedation. References from selected articles were also reviewed for additional material. Study Selection and Data Extraction: Experimental and observational English-language studies that focused on the efficacy, safety, and pharmacoeconomics of dexmedetomidine in humans were selected. Data Synthesis: Dexmedetomidine is an α2-agonist used for sedation during procedures and in critical illness. Compared with placebo, use of dexmedetomidine during procedures was associated with decreased use of rescue midazolam and a similar degree of sedation compared with various agents used during surgery or for procedures. Use of long-term (>24 h) dexmedetomidine sedation is comparable to sedation with benzodiazepines in critically ill patients. In a Phase 4 study, dexmedetomidine was safe in dosages up to 1.4 μg/kg/hour for greater than 24 hours and did not produce rebound tachycardia or hypertension when abruptly discontinued. One small randomized controlled trial demonstrated decreased incidence of delirium, the primary endpoint, with dexmedetomidine compared with midazolam or propofol for sedation after cardiac valve surgery. Many, but not all, studies suggest that dexmedetomidine has a promising role in prevention and treatment of delirium in critically ill patients when delirium was studied as a secondary endpoint. Conclusions: Dexmedetomidine is an alternative for procedural sedation and can be used long-term (>24 h) in critically ill patients, in dosages up to 1.5 μg/kg/hour. More studies are needed to better define the role of dexmedetomidine in preventing and treating delirium.

Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study

IntroductionWhile propofol is associated with an infusion syndrome (PRIS) that may cause death, the incidence of PRIS is unknown. Determining the incidence of PRIS and the frequency of PRIS-related clinical manifestations are key steps prior to the completion of any controlled studies investigating PRIS. This prospective, multicenter study sought to determine the incidence of PRIS and PRIS-related clinical manifestations in a large cohort of critically ill adults prescribed propofol.MethodsCritically ill adults from 11 academic medical centers administered an infusion of propofol for [>/=] 24 hours were monitored at baseline and then on a daily basis until propofol was discontinued for the presence of 11 different PRIS-associated clinical manifestations and risk factors derived from 83 published case reports of PRIS.ResultsAmong 1017 patients [medical (35%), neurosurgical (25%)], PRIS (defined as metabolic acidosis plus cardiac dysfunction and [>/=] 1 of: rhabdomyolysis, hypertriglyceridemia or renal failure occurring after the start of propofol therapy) developed in 11 (1.1%) patients an average of 3 (1-6) [median (range)] days after the start of propofol. While most (91%) of the patients who developed PRIS were receiving a vasopressor (80% initiated after the start of propofol therapy), few received a propofol dose >83 mcg/kg/min (18%) or died (18%). Compared to the 1006 patients who did not develop PRIS, the APACHE II score (25 +/- 6 vs 20 +/- 7, P = 0.01) was greater in patients with PRIS but both the duration of propofol use (P = 0.43) and ICU length of stay (P = 0.82) were similar.ConclusionsDespite using a conservative definition for PRIS, and only considering new-onset PRIS clinical manifestations, the incidence of PRIS slightly exceeds 1%. Future controlled studies focusing on evaluating whether propofol manifests the derangements of critical illness more frequently than other sedatives will need to be large. These studies should also investigate the mechanism(s) and risk factors for PRIS.

Dexmedetomidine‐Associated Bradycardia Progressing to Pulseless Electrical Activity: Case Report and Review of the Literature

Dexmedetomidine is an α2‐agonist indicated for sedation in critically ill patients and procedural sedation in nonintubated patients. It is a distinctive sedative because it does not cause respiratory depression, but it may cause hypotension and bradycardia. We describe a 74‐year‐old man who was receiving dexmedetomidine for agitation and experienced progressive bradycardia. The patient experienced a postoperative myocardial infarction 3 days after repair of an abdominal aortic aneurysm. A dexmedetomidine infusion was started at 0.11 μg/kg/hour, without a loading dose, for agitation; the patients heart rate was 123 beats/minute and blood pressure was 147/70 mm Hg, both within normal limits. Over the next 6 hours, the dexmedetomidine infusion rate was increased to a maximum of 0.7 μg/kg/hour; the patients heart rate progressively decreased to 21 beats/minute, followed by pulseless electrical activity. After 2 minutes of chest compressions and an intravenous bolus of atropine 0.4 mg, the patient regained a pulse. Dexmedetomidine was discontinued, and the patients heart rate and blood pressure returned to within normal limits. The patient was discharged home 7 days later without any cardiac or neurologic sequelae. Clinicians need to be educated about the potential for dexmedetomidine to cause bradycardia progressing to pulseless electrical activity, and patients need to be closely monitored. Patients who receive dexmedetomidine and develop a greater than 30% decrease in heart rate may be at high risk for severe bradycardia leading to pulseless electrical activity. We urge caution when using dexmedetomidine, especially in patients with significant cardiac disease.

A new dosing protocol reduces dexmedetomidine-associated hypotension in critically ill surgical patients

BACKGROUND Although no ideal sedative exists, dexmedetomidine is unique because it produces sedation and analgesia without decreasing the respiratory drive. Hemodynamic responses to dexmedetomidine are variable and dependent on the patient population. Our initial experience was associated with an unacceptable incidence of hypotension and bradycardia. We evaluated occurrence of hypotension and bradycardia in critically ill surgical patients receiving dexmedetomidine before and after implementation of a dosing protocol. METHODS This is a retrospective chart review of all admissions to a university medical center-based, 44-bed surgical intensive care unit pre and post protocol implementation. RESULTS Forty-four patients received dexmedetomidine including 19 historic controls and 25 dosed via protocol. Both groups had comparable demographics and initial and maximum dosages of dexmedetomidine. Use of the dosing protocol resulted in fewer dosage changes (mean +/- standard deviation, 4.8 +/- 3.8 compared to 7.8 +/- 3.9; P = .014) and fewer episodes of hypotension (16% vs 68.4%; P = .0006) but did not influence bradycardic episodes (20% vs 15.5%; P > .99). CONCLUSION We found that use of a protocol that increases the time interval between dosage adjustments may reduce dexmedetomidine-associated hypotension.

Comorbidity-Polypharmacy Scoring Facilitates Outcome Prediction in Older Trauma Patients

To determine the association between comorbidity–polypharmacy score (CPS) and clinical outcomes in a large sample of older trauma patients, focusing on outcome prognostication.

Contrast Medium‐Induced Nephrotoxicity: Pathophysiology and Prevention

Contrast medium‐induced nephrotoxicity (CMN) is a common form of iatrogenic acute renal failure. Typically, patients experience changes in serum creatinine or creatinine clearance between 1 and 5 days after exposure to a contrast medium, but they rarely require dialysis. The mechanism for CMN is not understood, but renal insufficiency, dehydration, and congestive heart failure are risk factors. The frequency of CMN with high‐osmolality versus low‐osmolality media is controversial. Prophylaxis can reduce CMN. Of many different strategies, hydration with normal saline before and after exposure offers the best protection with the fewest adverse effects.

High-Dose Dexmedetomidine for Sedation in the Intensive Care Unit: An Evaluation of Clinical Efficacy and Safety

BACKGROUND: Dexmedetomidine is an α2-receptor agonist used for sedation in the intensive care unit (ICU). Although dexmedetomidine is labeled for sedation in critically ill patients at doses up to 0.7 μg/kg/h, recent studies have used more liberal dosing regimens. However, to our knowledge, no study has assessed the clinical impact of doses greater than 0.7 μg/kg/h when compared to doses within the Food and Drug Administration-approved labeling. OBJECTIVE: To compare the clinical efficacy and safety of high (HD) and low (LD) dses of dexmedetomidine for sedation in the ICU. METHODS: This retrospective study included a sample of patients who received dexmedetomidine in medical, surgical, medical/surgical, and cardiothoracic ICUs between January 1, 2008, and December 1, 2009. Patients were included in the LD group if their maximum dose was less than 0.7 μg/kg/h or in the HD group if any dose was more than 0.7 μg/kg/h. Efficacy was determined by the percentage of Richmond Agitation and Sedation Scale (RASS) scores for each patient maintained at goal sedation (-1 to +1), and safety was determined by the incidence of hypotension and bradycardia. RESULTS: Forty-three of 133 patients received HD dexmedetomidine. Patients in the LD group had a significantly higher percentage of RASS scores at goal (60.0% vs 48.6%; p = 0.03), while those in the HD group experienced a higher percentage of RASS scores classified as undersedated (19.2% vs 4.9%; p = 0.001). There was no significant difference in the incidence of hypotension or bradycardia between groups. CONCLUSIONS: Patients treated with HD dexmedetomidine had fewer RASS scores at goal. Our data suggest that increasing the dose of dexmedetomidine may not enhance sedation efficacy or lead to an increased incidence of adverse effects. Patients who have not achieved goal sedation at doses of 0.7 μg/kg/h or less may not respond further to increased doses.

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.