Increased use in propofol and reported patterns of adverse events among anesthetics in Korea.

BACKGROUND: Propofol is an addictive drug, and the problem of its abuse and dependence has occurred. To compare the safety profiles of propofol and other similar anesthetics such as diazepam, lorazepam, and midazolam, we evaluated their uses and related adverse drug reactions (ADRs) using Korean Adverse Event Reporting System (KAERS) data. METHODS: The domestic consumption data and the ADR reports of four anesthetics from 2008 to 2012 were retrieved. ADR proportions were calculated using defined daily dose/1000 inhabitants/day (DID) for the denominator. The patient's characteristics were compared among the four drugs statistically, and the types of ADRs were analyzed. RESULTS: The consumption and ADR reports increased during the study period, particularly in the cases of propofol and midazolam. Lorazepam showed the highest overall and serious ADR proportions (220.81 reports/DID, 58.47 reports/DID, respectively); however, with respect to death proportion, propofol was the first (19.21 reports/DID). Also, ADRs related to drug addiction were mainly observed in the propofol group. CONCLUSIONS: Four anesthetics were different with regard to the consumption and proportion or the type of ADRs. The use of propofol increased more than 2 times, and propofol showed the highest ADR proportions in death and drug addiction cases among the four anesthetics.

Clinical and economic impact of substituting dexmedetomidine for propofol due to a US drug shortage: examination of coronary artery bypass graft patients at an urban medical centre.

BACKGROUND: Propofol has reduced healthcare costs in coronary artery bypass graft (CABG) surgery patients by decreasing post-operative duration of mechanical ventilation. However, the US shortage of propofol necessitated the use of alternative agents. OBJECTIVE: This study sought to evaluate clinical and economic implications of substituting dexmedetomidine for propofol in patients undergoing CABG surgery. METHODS: This was a retrospective cohort study. Patients undergoing isolated, elective CABG surgery and sedated with either propofol or dexmedetomidine during the study period were included. The cohorts were matched 1:1 based on important characteristics. The primary outcome was the number of patients achieving a post-operative duration of mechanical ventilation ≤6 h. Secondary outcomes were post-operative intensive care unit (ICU) length of stay (LOS) ≤48 h, total post-operative LOS ≤5 days, the need for adjunctive opioid therapy and associated cost savings. Variables recorded included patient demographics, co-morbid medical conditions, health risks, sedation drug doses, post-operative medical complications and sedation-related adverse events. Univariate and multivariate analyses were completed to examine the relationship between these covariates and post-operative LOS. The cost analysis consisted of examination of the net financial benefit (or cost) of choosing dexmedetomidine versus propofol in the study population, with utilisation observed in the study converted to costs using institutional data from the Premier database. RESULTS: Eighty-four patients were included, with 42 patients per cohort. Mechanical ventilation duration ≤6 h was achieved in 24 (57.1 %) versus 7 (16.7 %) in the dexmedetomidine and propofol cohorts, respectively (p < 0.001). More patients treated with dexmedetomidine achieved ICU LOS ≤48 h (p < 0.05) and total hospital LOS ≤5 days (p < 0.05), as compared with the propofol group. Multivariate analysis revealed that having one or more post-operative medical complication was the most significant predictor of increased post-operative LOS, whereas choosing dexmedetomidine was also significant in terms of reduced post-operative LOS. The estimated net financial benefit of choosing dexmedetomidine versus propofol was US$2,613 per patient (year 2012 value). CONCLUSIONS: Findings suggest that use of dexmedetomidine as an alternative to propofol for sedation of CABG patients post-operatively contributes to reduced mechanical ventilation time, ICU LOS and post-operative LOS. Higher drug costs resulting from the propofol shortage were offset by savings in post-operative room and board costs. Additional savings may be possible by preventing medical complications to the extent possible.

Impact of a national propofol shortage on duration of mechanical ventilation at an academic medical center.

OBJECTIVE: To measure the impact of a national propofol shortage on the duration of mechanical ventilation. DESIGN: Before-after study. SETTING: Three, noncardiac surgery, adult intensive care units at a 320-bed academic medical center. PATIENTS: Consecutive patients requiring mechanical ventilation ≥48 hrs, administered a continuously infused sedative ≥24 hrs, extubated, and successfully discharged from the intensive care unit were compared between before (December 1, 2008 to May 31, 2009) and after (December 1, 2009, to May 31, 2010) a propofol shortage. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Sedation drug use and common factors affecting time on mechanical ventilation were collected and if found either to differ significantly (p ≤ .10) between the two groups or to have an unadjusted significant association (p ≤ .10) with time on mechanical ventilation were included in a multivariable model. The unadjusted analyses revealed that the median (interquartile range) duration of mechanical ventilation increased from 6.7 (9.8; n = 153) to 9.6 (9.5; n = 128) days (p = .02). Fewer after-group patients received ≥24 hrs of continuously infused propofol (94% vs. 15%, p < .0001); more received ≥24 hrs of continuously infused lorazepam (7% vs. 15%, p = .037) and midazolam (30% vs. 81%, p < .0001). Compared with the before group, the after group was younger, had a higher admission Acute Physiology and Chronic Health Evaluation II score, was more likely to be admitted by a surgical service, have acute alcohol withdrawal, and be managed with pressure-controlled ventilation as the primary mode of mechanical ventilation. Of these five factors, only the Acute Physiology and Chronic Health Evaluation II score, admission service, and use of a pressure-controlled ventilation affected duration of mechanical ventilation across both groups. Although a regression model revealed that Acute Physiology and Chronic Health Evaluation II score (p < .0001), admission by a medical service (p = .009), and use of pressure-controlled ventilation (p = .02) each affected duration of mechanical ventilation in both groups, inclusion in either the before- or after-propofol shortage groups (i.e., high vs. low use of propofol) did not affect duration of mechanical ventilation (p = .35). CONCLUSIONS: An 84% decrease in propofol use in the adult intensive care units at our academic institution as a result of a national shortage did not affect duration of mechanical ventilation.

Effect of a dexmedetomidine substitution during a nationwide propofol shortage in patients undergoing coronary artery bypass graft surgery.

STUDY OBJECTIVE: To assess the effect of substituting dexmedetomidine for propofol during a nationwide propofol shortage on postoperative time to extubation and opioid requirements in patients who underwent coronary artery bypass graft (CABG) surgery. DESIGN: Retrospective case-control study. SETTING: Single-center cardiothoracic intensive care unit (ICU) in a tertiary academic medical center. PATIENTS: Seventy adults undergoing isolated, primary, elective CABG who received dexmedetomidine between April 1 and June 30, 2010, during the propofol shortage (35 patients [cases]) or who received propofol between January 1 and March 31, 2010, or between July 1 and September 30, 2010 (35 patients [controls]) for postoperative sedation were included. Patients in the dexmedetomidine group were matched 1:1 to patients in the propofol group based on age, sex, weight, number of vessels bypassed, preoperative ejection fraction, cardiopulmonary bypass time, and aortic cross-clamp time. MEASUREMENTS AND MAIN RESULTS: The primary outcome consisted of opioid requirements in the first 12 hours after arrival to the ICU in the dexmedetomidine- and propofol-treated patients. Secondary outcomes included the time to extubation (from ICU admission until extubation) and opioid requirements in the first 24 hours. No significant demographic differences were noted between treatment groups. Median opioid requirements in the first 12 hours, as measured by morphine equivalents, were 8.0 mg in the propofol group and 7.0 mg in the dexmedetomidine group (p=0.1). Similarly, at 24 hours, opioid requirements were 16.7 and 17.3 mg in the propofol and dexmedetomidine groups, respectively (p=0.4). The time to extubation demonstrated that patients in the propofol group were extubated at a median of 300 minutes and patients in the dexmedetomidine group were extubated at a median of 318 minutes after ICU arrival (p=0.5). CONCLUSION: No statistically significant differences were noted between the propofol and dexmedetomidine groups when assessing the outcomes of opioid requirements and the time to extubation. A multicenter, prospective, randomized, blinded study is needed to determine the optimal sedative after CABG surgery.

Impact of addition of propofol to ED formulary.

STUDY OBJECTIVES: Access to propofol remains a challenge for many emergency physicians. This report examines changes in patient care after the introduction of propofol to an emergency department formulary. METHODS: The Procedural Sedation in the Community Emergency Department registry is a prospective multicentered database of community emergency physician-directed procedural sedation cases. Medication selection and patient outcome were compared at a single Procedural Sedation in the Community Emergency Department registry study site before and after credentialing of emergency physicians for the use of propofol. Analysis was done through analysis of variance and χ(2) test. RESULTS: Over a 36-month period, 573 patients were entered into the registry from the single study site, 255 before and 318 after propofol introduction. The percentage of propofol use increased from 26% of procedural sedation cases in the first 3 months of availability to 69% in the final 3 months analyzed. Before propofol use, 46% of cases were completed with a single agent compared with after propofol use, in which 66% were completed with a single agent (P < .001). Complications decreased from 9% of patients before propofol use to 3% of patients after propofol use (P < .05), whereas sedation failures decreased from 5.1% to 4.1% (P < .02). CONCLUSION: Granted access to propofol, emergency physicians will preferentially use this medication over prior procedural sedation agents with fewer procedural sedation complications and greater procedural success.