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Effects of remifentanil with or without midazolam pretreatment on the 95% effective dose of propofol for loss of consciousness during induction: A randomized, clinical trial.

ABSTRACT: Propofol is a rapid, efficient hypnotic agent with antiemetic effects. However, a high dosage is related to hemodynamic abnormalities such as hypotension and bradycardia. Pretreatment with remifentanil can decrease injection pain and stabilize hemodynamics during the induction period. Remifentanil or midazolam in combination with propofol can provide synergistic or additive effects during anesthesia induction. However, the hypnotic doses of propofol required in patients who receive pretreatment with remifentanil or midazolam remain unclear.Patients aged 20 to 50 years who were scheduled to undergo surgery under general anesthesia were enrolled in this study. The patients were randomized into 3 groups using a computer-generated randomization table. Patients in Group P (Propofol) received only propofol for loss of consciousness, those in Group PR (Propofol-Remifentanil) received remifentanil prior to propofol, and those in Group PMR (Propofol-Midazolam-Remifentanil) received remifentanil and midazolam prior to propofol. After propofol administration, loss of both the eyelash reflex and verbal response represented success. The 95% effective dose of propofol for loss of consciousness in each group, which was the primary outcome, was determined using a modified biased coin up-and-down method.A total of 124 patients were initially enrolled. Of these, 4 were excluded, and the remaining 120 patients were randomized to each (n?=?40) of the 3 groups. The 95% effective dose of propofol for loss of consciousness was 1.74?, 1.38, and 0.92?mg/kg in Groups P, PR, and PMR, respectively. Blood pressure decreased at 2?minutes after propofol administration in all the groups. However, compared with Group P, Groups PR and PMR exhibited a significant decrease in blood pressure.The effective dose of propofol for loss of consciousness could be decreased by 21% and 47% when remifentanil pretreatment was used without and with midazolam, respectively. However, the decrease in blood pressure was greater with pretreatment than sole propofol use. These findings suggest that the combination of remifentanil with or without midazolam may have no benefit on hemodynamic stability during induction using propofol.NCT02536690 (clinicaltrials.gov).

SUBMITTER: Koh JC

PROVIDER: S-EPMC5728976 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Effects of remifentanil with or without midazolam pretreatment on the 95% effective dose of propofol for loss of consciousness during induction: A randomized, clinical trial.

Koh Jae Chul JC Park Juyeon J Kim Na Young NY You Ann Hee AH Ko Seo Hee SH Han Dong Woo DW

Medicine 20171201 49

<h4>Background</h4>Propofol is a rapid, efficient hypnotic agent with antiemetic effects. However, a high dosage is related to hemodynamic abnormalities such as hypotension and bradycardia. Pretreatment with remifentanil can decrease injection pain and stabilize hemodynamics during the induction period. Remifentanil or midazolam in combination with propofol can provide synergistic or additive effects during anesthesia induction. However, the hypnotic doses of propofol required in patients who re ...[more]

PMID: 29245361

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Project description:BackgroundOlder people are more vulnerable to hemodynamic instability caused by propofol due to their decreased initial distribution volume and increased sensitivity to propofol. Midazolam or remifentanil can often be coadministered because of their synergistic or additive effects with propofol as well as amnesic properties and the blockade of sympathetic stimulation. However, no study has confirmed the appropriate dose of propofol for loss of consciousness in aged patients when administered with other drugs, including opioids or benzodiazepines.MethodsPatients >65 years scheduled for general anesthesia were enrolled. The patients were randomized into 3 groups using a computer-generated randomization table. Patients in group P (propofol) received only propofol for loss of consciousness, those in group PR (propofol-remifentanil) received remifentanil before propofol, and those in group PMR (propofol-midazolam-remifentanil) received remifentanil and midazolam before propofol. After propofol administration, loss of both eyelash reflex and verbal response represented success. The 95% effective dose of propofol for loss of consciousness in each group, which was the primary outcome, was determined using a modified biased coin up-and-down method.ResultsIn total, 120 patients were randomized into the 3 groups (n = 40). The 95% effective dose of propofol for loss of consciousness was 1.13, 0.87, and 0.72 mg/kg in groups P, PR, and PMR, respectively. The mean blood pressure (MBP) in group PMR was more significantly decreased before propofol injection (P = .041) as well as 2 minutes (P = .005) and 3 minutes after propofol administration (P<.001), compared with group P, but there were no intergroup differences at other time points.ConclusionsThe effective dose of propofol for loss of consciousness in elderly patients could be decreased by 23% and 36% when remifentanil pretreatment was used without and with midazolam, respectively. However, the decrease in MBP was greater with remifentanil and midazolam pretreatment than with propofol alone. These findings suggest that pretreatment with midazolam for propofol infusions with remifentanil in elderly patients should be cautiously used, due to hemodynamic instability during induction.

Project description:BackgroundIntravenous use of sufentanil can elicit cough. This study aimed to evaluate the inhibitory effect of pre-injection of a mall dose of remifentanil on sufentanil-induced cough during the induction of general anesthesia.MethodsThis prospective, randomized, controlled trial was conducted from January 10, 2019 to March 01, 2019. A total of 100 patients undergoing elective surgery under general anesthesia were enrolled, and at last 84 patients were included and randomly allocated into two equal size groups (n =?42): Patients in the Remifentanil group (R group) received an intravenous infusion of remifentanil 0.3??g/kg (diluted to 2?ml) 1?min before sufentanil injection; patients in the Control group (C group) received 2?ml of normal saline (NS) at the same time point. Injections of patients in both groups were completed within 5?s. Then, sufentanil 0.5??g/kg was injected within 5?s and the number of coughs that occurred within 1?min after sufentanil injection were recorded. One minute after sufentanil injection, etomidate 0.3?mg/kg and cisatracurium 0.15?mg/kg were given for general anesthesia induction irrespective of the presence or absence of cough. The mean arterial pressure (MAP) and heart rate (HR) at time points just before remifentanil pretreatment administration (T0), 3?min after administration (T1), 1?min after intubation (T2), and 3?min after intubation (T3) were recorded.ResultsThe incidence of cough in patients in the R group and C group was 4.8 and 31%, respectively. Compared with group C, the incidence and severity of cough in group R was significantly lower (P <?0.01). No significant differences were observed in MAP and HR at the time of general anesthesia induction between the two groups (P >?0.05).ConclusionPretreatment with a small dose of remifentanil effectively and safely reduced the incidence and severity of cough induced by sufentanil during anesthesia induction and can be used as an alternative treatment to inhibit coughing caused by sufentanil.Trial registrationChinese Clinical Trial Registry (ChiCTR1900020587, registered date: January 9, 2019), http://www.chictr.org.cn.

Project description:On sedation motivated by the clinical needs for safety and reliability, recent studies have attempted to identify brain-specific signatures for tracking patient transition into and out of consciousness, but the differences in neurophysiological effects between 1) the sedative types and 2) the presence/absence of surgical stimulations still remain unclear. Here we used multimodal electroencephalography-functional near-infrared spectroscopy (EEG-fNIRS) measurements to observe electrical and hemodynamic responses during sedation simultaneously. Forty healthy volunteers were instructed to push the button to administer sedatives in response to auditory stimuli every 9-11 s. To generally illustrate brain activity at repetitive transition points at the loss of consciousness (LOC) and the recovery of consciousness (ROC), patient-controlled sedation was performed using two different sedatives (midazolam (MDZ) and propofol (PPF)) under two surgical conditions. Once consciousness was lost via sedatives, we observed gradually increasing EEG power at lower frequencies (<15 Hz) and decreasing power at higher frequencies (>15 Hz), as well as spatially increased EEG powers in the delta and lower alpha bands, and particularly also in the upper alpha rhythm, at the frontal and parieto-occipital areas over time. During ROC from unconsciousness, these spatio-temporal changes were reversed. Interestingly, the level of consciousness was switched on/off at significantly higher effect-site concentrations of sedatives in the brain according to the use of surgical stimuli, but the spatio-temporal EEG patterns were similar, regardless of the sedative used. We also observed sudden phase shifts in fronto-parietal connectivity at the LOC and the ROC as critical points. fNIRS measurement also revealed mild hemodynamic fluctuations. Compared with general anesthesia, our results provide insights into critical hallmarks of sedative-induced (un)consciousness, which have similar spatio-temporal EEG-fNIRS patterns regardless of the stage and the sedative used.

Project description:BackgroundVasopressors are frequently used to increase blood pressure in order to ensure sufficient cerebral perfusion and oxygenation (CPO) during hypotensive periods in anaesthetized patients. Efficacy depends both on the vasopressor and anaesthetic protocol used. Propofol-remifentanil total intravenous anaesthesia (TIVA) is common in human anaesthesia, and dexmedetomidine is increasingly used as adjuvant to facilitate better haemodynamic stability and analgesia. Little is known of its interaction with vasopressors and subsequent effects on CPO. This study investigates the CPO response to infusions of norepinephrine and phenylephrine in piglets during propofol-remifentanil and propofol-remifentanil-dexmedetomidine anaesthesia. Sixteen healthy female piglets (25-34 kg) were randomly allocated into a two-arm parallel group design with either normal blood pressure (NBP) or induced low blood pressure (LBP). Anaesthesia was induced with propofol without premedication and maintained with propofol-remifentanil TIVA, and finally supplemented with continuous infusion of dexmedetomidine. Norepinephrine and phenylephrine were infused in consecutive intervention periods before and after addition of dexmedetomidine. Cerebral perfusion measured by laser speckle contrast imaging was related to cerebral oxygenation as measured by an intracerebral Licox probe (partial pressure of oxygen) and transcranial near infrared spectroscopy technology (NIRS) (cerebral oxygen saturation).ResultsDuring propofol-remifentanil anaesthesia, increases in blood pressure by norepinephrine and phenylephrine did not change cerebral perfusion significantly, but cerebral partial pressure of oxygen (Licox) increased following vasopressors in both groups and increases following norepinephrine were significant (NBP: P = 0.04, LBP: P = 0.02). In contrast, cerebral oxygen saturation (NIRS) fell significantly in NBP following phenylephrine (P = 0.003), and following both norepinephrine (P = 0.02) and phenylephrine (P = 0.002) in LBP. Blood pressure increase by both norepinephrine and phenylephrine during propofol-remifentanil-dexmedetomidine anaesthesia was not followed by significant changes in cerebral perfusion. Licox measures increased significantly following both vasopressors in both groups, whereas the decreases in NIRS measures were only significant in the NBP group.ConclusionsCerebral partial pressure of oxygen measured by Licox increased significantly in concert with the vasopressor induced increases in blood pressure in healthy piglets with both normal and low blood pressure. Cerebral oxygenation assessed by intracerebral Licox and transcranial NIRS showed opposing results to vasopressor infusions.

Dataset Information

Effects of remifentanil with or without midazolam pretreatment on the 95% effective dose of propofol for loss of consciousness during induction: A randomized, clinical trial.

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Effects of remifentanil with or without midazolam pretreatment on the 95% effective dose of propofol for loss of consciousness during induction: A randomized, clinical trial.

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