Opioid-related genetic polymorphisms do not influence postoperative opioid requirement: A prospective observational study.

BACKGROUND: Among the various factors that may influence the pharmacological response to opioids, genetic polymorphisms [single nucleotide polymorphisms (SNP)] have generated some interest. OBJECTIVES: To examine the influence on morphine dose requirements and adverse events in the postoperative period of four SNP [opioid receptor mu1 (OPRM1), ATP-binding cassette subfamily B, member 1 (ABCB1) ex-21 and ex-26, catechol-o-methyltransferase (COMT)] in candidate genes involved in morphine pharmacodynamics and pharmacokinetics. DESIGN: A single centre prospective study. SETTING: University Hospital, Paris, France, from 2 January 2007 to 15 November 2011. PATIENTS: A total of 438 white adults scheduled for major orthopaedic surgery (spine, hip and knee) under general anaesthesia. The main exclusion criteria were receiving opioids for chronic pain, nonopioid drugs within 2 days prior to surgery, pregnancy, renal insufficiency, sleep apnoea obstruction syndrome, morbid obesity, severe hepatic impairment, cognitive dysfunction. INTERVENTIONS: Assays of plasma concentrations of morphine and metabolites (morphine 3-glucuronide and morphine 6-glucuronide) were performed and common polymorphisms in four candidate genes [OPRM1 A118G rs1799971; P-glycoprotein (ABCB1) T3435C (rs1045642) and G2677T/A (rs2032582); COMT Val 158 Met (rs4680)] were analysed.Morphine was titrated by staff in the postanaesthesia care unit (PACU) and in the ward patient-controlled intravenous analgesia was used for 24 h. MAIN OUTCOME MEASURES: The dose of morphine required to achieve pain relief and the influence of SNP in genes involved in morphine pharmacodynamics and kinetics on morphine dose requirements. Secondary endpoints were the concentrations of morphine, morphine 6-glucuronide and morphine 3-gluguronide, the proportion of patients requiring a rescue analgesic and the proportion of morphine-related adverse events. RESULTS: A total of 404 patients completed the study to final analysis. The mean ±â€ŠSD morphine dose to achieve pain relief was 15.8 ±â€Š8.8 mg in the PACU and 22.7 ±â€Š18.6 mg during patient-controlled intravenous administration. Morphine-related adverse events were observed in 37%. There was no relationship between any genetic polymorphisms and morphine dose, morphine 3-gluguronide and morphine 6-glucuronide concentration, morphine-related adverse events or pain level. In the PACU only, P-glycoprotein polymorphisms (ex-21; ex-26) were significantly associated with morphine concentration but the prediction of the model was poor (R = 0.04) CONCLUSION: No major relationship has been demonstrated between SNP of OPRM1, ABCB1, COMT and morphine requirement, pain level or adverse effects in the postoperative period. TRIAL REGISTRATION: NCT00822549 (www.clinicaltrials.gov).

Benefit of a single recruitment maneuver after an apnea test for the diagnosis of brain death.

INTRODUCTION: Many potential lung transplants are lost because of hypoxemia during donor management. We hypothesized that the apnea test, necessary to confirm the diagnosis of brain death in potential lung donors, was involved in the decrease in the ratio of partial pressure of arterial O2 to fraction of inspired O2 (PaO2/FiO2) and that a single recruitment maneuver performed just after the apnea test can reverse this alteration. METHODS: In this case-control study, we examined the effectiveness of the recruitment maneuver with a comparison cohort of brain dead patients who did not receive the maneuver. Patients were matched one-to-one on the basis of initial PaO2/FiO2 and on the duration of mechanical ventilation before the apnea test. PaO2/FiO2 was measured before (T1), at the end (T2) and two hours after apnea test (T3). RESULTS: Twenty-seven patients were included in each group. The apnea test was associated with a significant decrease in PaO2/FiO2 from 284 ± 98 to 224 ± 104 mmHg (P < 0.001). The decrease in PaO2/FiO2 between T1 and T3 was significantly lower in the recruitment maneuver group than in the control group (-4 (-68-57) vs -61 (-110--18) mmHg, P = 0.02). The number of potential donors with PaO2/FiO2 > 300 mmHg decreased by 58% (95% CI: 28-85%) in the control group vs 0% (95% CI: 0-34%) in the recruitment maneuver group (P < 0.001). CONCLUSIONS: The apnea test induced a decrease in PaO2/FiO2 in potential lung donors. A single recruitment maneuver performed immediately after the apnea test can reverse this alteration and may prevent the loss of potential lung donors.

Direct laryngoscopy should be procedure of choice in the airway management of patients with dental cellulitis.

CONTEXT: Airway management of patients with dental cellulitis can be difficult due to laryngeal deviation and oedema. Awake fibre-optic intubation has been recommended. OBJECTIVE: The aim of this study was to assess our routine procedure which is based mainly on direct laryngoscopy. DESIGN: This was a prospective observational study. SETTING: In a single centre between February 2008 and February 2009. PATIENTS: All patients suffering from dental cellulitis and requiring emergency surgery were included except pregnant women and patients under 18 years. INTERVENTION: Nasotracheal intubation by direct laryngoscopy under general anaesthesia was performed unless the supine position was not tolerated, or difficult mask ventilation or intubation was anticipated, when awake nasotracheal fibre-optic intubation was indicated. In the case of failure at the first attempt, orotracheal intubation by direct laryngoscopy was attempted. If failure persisted, tracheotomy was then performed. MAIN OUTCOME MEASURES: The principal endpoint was the incidence of difficult mask ventilation which was expected to be less than 5%. Secondary endpoints were the incidence of difficult tracheal intubation and tracheotomy. RESULTS: We included 127 consecutive patients (mouth opening 20±10 mm). One did not tolerate the supine position and was successfully intubated using the fiberscope. Among the 126 remaining, difficult mask ventilation did not occur [0%, 95% confidence interval (CI) 0-3%], 124 (98%) patients were intubated by direct laryngoscopy and two (2%) required tracheotomy. Retrognathia (odds ratio 8.2, 95% CI 1.3-50.1) and extension to oral floor (odds ratio 15.1, 95% CI 1.8-129.5) were significantly associated with the prediction of intubation failure at the first attempt. CONCLUSION: Most patients with dental cellulitis can be safely intubated through direct laryngoscopy even if mouth opening is limited.

Relationships between plasma concentrations of morphine, morphine-3-glucuronide, morphine-6-glucuronide, and intravenous morphine titration outcomes in the postoperative period.

Although intravenous morphine titration (IMT) is widely used to control moderate to severe postoperative pain, the relationships between plasma concentrations of morphine and its metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), and IMT outcomes in the postanesthesia care unit (PACU) have not been yet investigated. IMT was administrated as a bolus of 2 or 3 mg every 5 min. Titration was interrupted in case of pain relief (visual analog score ≤30), adverse events, sedation, or failure of morphine titration. Blood samples were collected at the end of morphine titration to determine plasma concentration of morphine and its two metabolites. Data from 214 patients were analyzed; 143 (67%) of the patients achieved complete pain relief, 39 (18%) experienced adverse events, and 32 (15%) failure of morphine titration. At the end of titration, there were no significant differences in morphine, M6G, M3G concentrations between sedated and nonsedated patients (32 vs. 42 ng/mL (P = 0.07), 38 vs. 45 ng/mL (P = 0.51), 300 vs. 342 ng/mL (P = 0.29), respectively), or patients with or without adverse events (40 vs. 41 ng/mL (P = 0.95), 37 vs. 46 ng/mL (P = 0.51), 287 vs. 340 ng/mL (P = 0.72), respectively). Our study demonstrated a lack of relationship between plasma concentrations or ratios of morphine, M3G, and M6G, with IMT outcomes in PACU. This result suggests that the kinetics of morphine and its metabolites have limited value for explaining clinical effects of morphine in this clinical setting.