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

Erdman MJ, Doepker BA, Gerlach AT, Phillips GS, Elijovich L, Jones GM. A comparison of severe hemodynamic disturbances between dexmedetomidine and propofol for sedation in neurocritical care patients. Crit Care Med. 2014 Jul;42(7):1696-702.

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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.

Dexmedetomidine use in the ICU: Are we there yet? (Pham)

Ahmed S, Murugan R. Dexmedetomidine use in the ICU: Are we there yet? Crit Care. 2013 May 31;17(3):320.

BACKGROUND: Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an alpha-2 agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort.

METHODS: OBJECTIVE: The objective was to determine the efficacy of dexmedetomidine versus midazolam or propofol (preferred usual care) in maintaining sedation, reducing duration of mechanical ventilation, and improving patients’ interaction with nursing care.

DESIGN: Two phase 3 multicenter, randomized, double-blind trials were conducted.

SETTING: The MIDEX (Midazolam vs. Dexmedetomidine) trial compared midazolam with dexmedetomidine in ICUs of 44 centers in nine European countries. The PRODEX (Propofol vs. Dexmedetomidine) trial compared propofol with dexmedetomidine in 31 centers in six European countries and two centers in Russia.

SUBJECTS: The subjects were adult ICU patients who were receiving mechanical ventilation and who needed light to moderate sedation for more than 24 hours.

INTERVENTION: After enrollment, 251 and 249 subjects were randomly assigned midazolam and dexmedetomidine, respectively, in the MIDEX trial, and 247 and 251 subjects were randomly assigned propofol and dexmedetomidine, respectively, in the PRODEX trial. Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials were employed.

OUTCOMES: For each trial, investigators tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were the ability of the patient to communicate pain (measured by using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol (midazolam, n = 233, versus dexmedetomidine, n = 227; propofol, n = 214, versus dexmedetomidine, n = 223) population.

RESULTS: Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% confidence interval (CI) 0.97 to 1.18), and dexmedetomidine/propofol ratio in time at target sedation was 1.00 (95% CI 0.92 to 1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours, interquartile range (IQR) 67 to 337) versus midazolam (164 hours, IQR 92 to 380; P = 0.03) but not with dexmedetomidine (97 hours, IQR 45 to 257) versus propofol (118 hours, IQR 48 to 327; P = 0.24). Patient interaction (measured by using VAS) was improved with dexmedetomidine (estimated score difference versus midazolam 19.7, 95% CI 15.2 to 24.2; P <0.001; and versus propofol 11.2, 95% CI 6.4 to 15.9; P <0.001). Lengths of ICU and hospital stays and mortality rates were similar. Dexmedetomidine versus midazolam patients had more hypotension (51/247 [20.6%] versus 29/250 [11.6%]; P = 0.007) and bradycardia (35/247 [14.2%] versus 13/250 [5.2%]; P <0.001).

CONCLUSIONS: Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved the ability of patients to communicate pain compared with midazolam and propofol. Greater numbers of adverse effects were associated with dexmedetomidine.

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Case report: profound hypotension after anesthetic induction with propofol in patients treated with rifampin. (Chandler)

Anesth Analg. 2013 Jul;117(1):61-4. PMID: 23687230

Rifampin is commonly used for the treatment of tuberculosis and staphylococcal infections, as well as for prevention of infection in cardiac valve and bone surgeries. We report a case of profound hypotension after anesthesia induction with propofol in a patient who was treated with two 600 mg doses of rifampin for prophylaxis of infection before surgery. In a retrospective case-control study of 75 patients, we confirmed this potentially serious drug-drug interaction. After rifampin, there was a significant and prolonged arterial blood pressure reduction when patients received propofol, but not thiopental.

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Effect of short-term propofol administration on pancreatic enzymes and lipid biochemistry in children between 1 month and 36 months. (Kamat/Pham)

Paediatr Anaesth. 2013 Apr;23(4):355-9. PMID: 23137103

BACKGROUND: Use of propofol in pediatric age group has been marred by reports of its adverse effects like hypertriglyceridemia and acute pancreatitis, although a causal relation has not yet been established.

OBJECTIVES: This prospective, clinical trial was carried out to evaluate the effects of short-term propofol administration on serum lipid profile and serum pancreatic enzymes in children of ASA physical status I and II aged between 1 month and 36 months.

METHODS: Anesthesia was induced with Propofol (1%) in the dose of 3 mg·kg(-1) intravenously and was maintained by propofol infusion (0.5%) at the rate of 12 mg·kg(-1·) h(-1) for the first 20 min and at 8 mg·kg(-1·) h(-1) thereafter. The mean dose of propofol administered was 12.02 ± 2.75 mg·kg(-1) (fat load of 120.2 ± 27.5 mg·kg(-1) ). Lipid profile, serum amylase, and lipase were measured before induction of anesthesia, at 90 min, 4 h, and finally 24 h after induction.

RESULTS: Serum lipase levels (P < 0.05), serum triglyceride levels (P < 0.05), and serum very low-density lipoproteins VLDL levels (P < 0.05) were raised significantly after propofol administration from baseline although remained within normal limits. Serum cholesterol levels and serum low-density lipoproteins LDL levels showed a statistically significant fall over 24 h. No significant changes in serum pancreatic amylase levels were seen (P > 0.05). None of the patients developed any clinical features of pancreatitis in the postoperative period.

CONCLUSION: We conclude that despite a small, transient increase in serum triglycerides and pancreatic enzymes, short-term propofol administration in recommended dosages in children of ASA status I and II aged between 1 month and 36 months does not produce any clinically significant effect on serum lipids and pancreatic enzymes.

© 2012 Blackwell Publishing Ltd.

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