Recovery after total intravenous anaesthesia using combined midazolam/alfentanil infusion and reversal with flumazenil

One of the major problems with total intravenous anaesthesia (TIVA) is postoperative sedation, possibly with respiratory depression. The aim of the present study was to evaluate the recovery characteristics after TIVA using a continuous infusion of a mixture of midazolam and alfentanil with flumazenil reversal before extubation. This method was compared to balanced anaesthesia using midazolam, alfentanil and nitrous oxide without flumazenil reversal. The degree of sedation was measured by reaction time test, Glasgow Coma Scale, cipher copying test and subtraction test. We found significantly faster reaction times postoperatively in the TIVA group (n = 15) compared to the balanced group (n = 13), despite larger doses of both midazolam (median 21 mg versus 9 mg) and alfentanil (median 5.9 mg versus 4.5 mg). The other tests revealed no difference between the groups. One patient became resedated after flumazenil. We conclude that the TIVA technique described here resulted in slightly better recovery characteristics, offering a usable alternative to balanced anaesthesia.     

Recovery from sufentanil anaesthesia for outpatient arthroscopy: a comparison with isoflurane

This study compares the recovery from sufentanil and isoflurane anaesthesia in patients undergoing outpatient arthroscopy of the knee under general anaesthesia. In 40 unpremedicated patients, divided at random into two groups, anaesthesia was induced with methohexitone and vecuronium bromide and, after intubation, maintained with nitrous oxide 66% in oxygen supplemented with sufentanil or isoflurane. Patients in Group A received sufentanil (1 microgram/kg) at induction and if necessary an incremental dose of 10 micrograms. Patients in Group B received 3% isoflurane prior to intubation and 0.9% during maintenance. Awakening from anaesthesia was more rapid with sufentanil than isoflurane. Recovery was assessed from the time patients took to open their eyes, to give correct answers to five questions and to recover from ocular imbalance. (Maddox wing test), and by comparing pre- and postoperative performance of a paper and pencil test (the p-deletion test). After 2 h, there was no difference between the two groups. Both anaesthetic techniques provided satisfactory operating conditions, but the sufentanil group showed a higher incidence of nausea and vomiting (45%) than the isoflurane group (15%).     

Induction agents for day-case anaesthesia A double-blind comparison of propofol and midazolam antagonised by flumazenil

Early postoperative recovery was studied using sedation scoring, measurement of flicker fusion frequency and completion of Trieger test figures in 60 male patients who presented for vasectomy under general anaesthesia as day patients. Anaesthesia was induced in groups 1 and 2 (20 patients each) with mean (SD) doses of 0.16 (0.04) mg/kg or 0.16 (0.03) mg/kg midazolam respectively; group 2 received flumazenil 0.55 (0.19) mg after completion of surgery. The remaining 20 patients (group 3) received propofol 1.50 (0.24) mg/kg. Anaesthesia was maintained with isoflurane vaporized in 33% oxygen and nitrous oxide in all patients. Flumazenil tended to improve tests of recovery after midazolam anaesthesia, but early recovery after propofol anaesthesia was associated with better psychomotor test results and less impairment of mental state as judged by sedation and amnesia scoring.     

Effects of the benzodiazepine antagonist flumazenil on postoperative performance following total intravenous anaesthesia with midazolam and alfentanil

Postoperative performance following total intravenous anaesthesia (TIVA) using midazolam and alfentanil was studied with and without the administration of a single dose of a benzodiazepine antagonist, flumazenil (Ro 15-1788). Performance was compared with a reference group anaesthetized with thiopentone, alfentanil and nitrous oxide. All patients were assessed by use of a rating scale which took into account the degree of sedation, amnesia, comprehension and cooperation as well as temporal and spatial orientation. There was a slow recovery following TIVA with somnolence and amnesia lasting several hours. Administration of flumazenil 1.0 mg i.v. at extubation caused a significant reduction of sedation (P less than 0.001) during the first postoperative hour, with patients fully awake or only lightly sedated, but was later followed by resedation. The patients of the reference group were moderately sedated during the observation period. Five and six hours postoperatively there was no difference between the groups. Amnesia was more profound in the groups that received midazolam; the effect of the antagonist could only be seen for 15 min after its administration. Comprehension and cooperation, as well as orientation, were equally good in the antagonist and in the reference group during the immediate postoperative period, whereas in the TIVA group a gradual improvement over the first hours was seen. In the antagonist group there was no increase in the number of analgesic requirements, no anxiety attacks or other adverse effects. It is concluded that flumazenil offers an improvement in postoperative performance following TIVA induced by midazolam and alfentanil, but the effects are of short duration.     

Recovery from total intravenous anaesthesia. Propofol versus midazolam-flumazenil

The aim of this study was to compare recovery assessed with the Newman, deletion af a's and postbox tests after total intravenous anaesthsia for procedures lasting more than 90 min, with either propofol (PPF) or midazolam (MDZ), reversed or not by flumazenil (FMZ). Thirty patients scheduled for peripheral surgery were randomly allocated to 3 groups of 10, receiving by continuous infusion until the end of surgery either PPF (n = 10) or MDZ (n = 20) combined with alfentanil. FMZ was administered thereafter to 10 patients receiving MDZ until they opened their eyes on command or to a maximum dose of 1 mg. Recovery tests were performed 45, 90 and 180 min after the end of anaesthesia. Results were analysed with non-parametric tests. Recovery scores were significantly better in the PPF group at all times, reaching control values at 180 min for the three first tests. FMZ reversal did not improve the scores compared to those resulting from MDZ alone. This study provides further data in favour of PPF as far as rapid and complete recovery is concerned. The efficiency of FMZ is incomplete and only transient when administered in a single dose.     

Recovery from sevoflurane and isoflurane anaesthesia after outpatient gynaecological laparoscopy

As the low blood solubility (blood gas partition coefficient 0.69) of sevoflurane suggests a rapid emergence from anaesthesia, recovery from sevoflurane anaesthesia was compared to isoflurane in outpatient gynaecological laparoscopy. Fifty ASA I or II, consenting women participated in a randomised, controlled and single blind study. The patients received, after induction of anaesthesia with propofol, either sevoflurane or isoflurane, both with 67% nitrous oxide in oxygen, for maintenance of anaesthesia. The study drug was administered at 1 MAC (end tidal concentration 0.6% for sevoflurane and 0.5% for isoflurane) but adjusted in 0.5 MAC steps, if clinically indicated. Before the end of surgery the end tidal concentration of the study drug was reduced to 0.5 MAC. Recovery assessments were made from the time anaesthetic gases were discontinued. The subjects were able to open eyes in 2.3 (0.8–7.0) min and 4.1 (2.0–6.8) min, orientate in 2.8 (1.0–6.8) min and 4.7 (2.2–8.3) min and follow orders in 2.6 (0.7–6.8) min and 4.3 (1.2–7.3) min, in the sevoflurane and isoflurane groups, respectively ( P <0.05) [median (range)]. Walking was achieved in 72 (24–464) min and 66 (35—134) min, tolerance of oral fluids in 37 (15–88) min and 35 (45–161) min and voiding in 262 (96–459) min and 217 (52–591) min in the sevoflurane and isoflurane groups, respectively (NS). Overall home readiness was achieved in 281 (96–708) min after sevoflurane group and 242 (96–591) min after isoflurane (NS). Postoperative nausea and vomiting was common in both groups (55% for sevoflurane and 45% for isoflurane) and contributed to three subjects in the sevoflurane group and four in the isoflurane group being admitted to hospital.     

Total intravenous anaesthesia with midazolam and flumazenil in outpatient clinics

Total intravenous anaesthesia with midazolam and alfentanil, reversed with the benzodiazepine antagonist flumazenil, was studied in patients admitted for outpatient gynaecological dilatation and curettage. One hundred patients were randomly allocated to four groups with different anaesthetic techniques: I: alfentanil and thiopentone induction, 66% N2O maintenance; II: alfentanil and midazolam sedation prior to isoflurane and N2O induction and maintenance; III: midazolam and alfentanil induction; oxygen/air, placebo reversal; IV: midazolam and alfentanil induction, oxygen/air, flumazenil reversal. All methods of anaesthesia proved satisfactory with no serious side-effects or complications. Induction was faster in Group I (26 s) compared with Group III and IV (37-38 s) and Group I (62 s). Respiration was less depressed in Group II compared with the other groups. Recovery function was better in Group IV during the first 30 postoperative min and worse in Group III during the first 120 postoperative min compared with the other groups. Reduced performances in P-deletion and 4-choice reaction-time tests in the midazolam patients were not reversed by 0.5 mg flumazenil, suggesting that flumazenil did not antagonize all benzodiazepine effects in our patients. Postoperative amnesia was most pronounced in Group III. There was no significant difference in patient function 7 h postoperatively, at home in the evening or during the next days. We conclude that total intravenous anaesthesia with alfentanil and midazolam with flumazenil reversal is a promising technique for short outpatient anaesthetic procedures.     

Evaluation of postural stability by computerised posturography following outpatient paediatric anaesthesia. Comparison of propofol/alfentanil/ N2O anaesthesia with thiopentone/halothane/N2O anaesthesia

Simple clinical tests, like Romberg's test or a walking test, have proved to be inadequate guidelines for safe discharge after outpatient anaesthesia (1, 2). A randomised study was therefore planned to compare postural stability measured by computerised posturography in 31 oral midazolam-atropine premedicated children aged 6.9 (s.e. 0.4) years who had been anaesthetised with either propofol/aIfentanil/N₂O or thiopentone/ halothane/N₂O. The sway velocity of the children was measured before premedication and 1, 2 and 3 h after the end of anaesthesia. Results show that sway velocity had returned to baseline values 3 h after the end of anaesthesia in all children who had received propofoI/alfentanil/N₂O and in 12 of the 15 children who had received thiopentone/halothane/N₂O. The quantified version of the Romberg test performed with eyes open or closed was not impaired after anaesthesia, compared with the control values, indicating that in children poor equilibrium is not compensated by vision. The clinical recovery with respect to the times to eye opening, to responding to command or to being fully awake did not differ between the two anaesthesia methods. On the basis of recovery assessed by postural stability, propofol/alfentanil/N₂O anaesthesia was not preferable to thiopentone/halothane/N_sO anaesthesia after minor paediatric otolaryngological surgery.     

Recovery and discharge of patients after long propofol infusion vs isoflurane anaesthesia for ambulatory surgery

Fifty unpremedicated patients scheduled for outpatient restorative dentistry and/or oral surgery lasting 2 to 4 h were anaesthetized with either propofol infusion or isoflurane inhalation. Before induction of anaesthesia with propofol (2.5 mg.kg-1), all patients were given 75 mg of diclofenac and 0.01 mg.kg-1 vecuronium intravenously. Intubation was facilitated with suxamethonium (1.5 mg.kg-1) and anaesthesia was maintained in random order either with propofol infusion (12 mg.kg-1.h-1 for the first 20 min, 9 mg.kg-1.h-1 for the next 20 min, and 6 mg.kg-1.h-1 for the rest of the anaesthesia) or with isoflurane (inspired concentration 1-2.5%), both with nitrous oxide and oxygen (30%). The patients breathed spontaneously using a non-rebreathing circuit. Patients given propofol infusion became re-orientated faster (11.0 +/- 5.5 min vs. 16.5 +/- 7.5 min; P less than 0.01) and at 30 min walked along a straight line better (P less than 0.01). At 60 min, none of the propofol patients displayed an unsteady gait, whereas 11 of the 25 isoflurane patients did (P less than 0.001). None of the patients receiving propofol had emesis at the clinic, compared with 10 of the 25 patients receiving isoflurane (P less than 0.001). The overall incidence of emesis was 2 of 25 and 14 of 25 in the propofol and isoflurane groups, respectively (P less than 0.01). Patients receiving propofol were discharged home earlier than patients receiving isoflurane (80 +/- 14 min and 102 +/- 32 min, respectively; P less than 0.01). It is concluded that propofol allows early discharge of patients, even after long anaesthesias.     

Anaesthesia techniques for midazolam and flumazenil - an overview

Midazolam, the latest henzodiazepine agonist, may be used in doses of 0.15 to 0.2 mg.kg^-1 for induction of anaesthesia. It provides good correlation between plasma concentration and anaesthetic effect with an interindividual variability of only 20–25%. On this basis, dosage recommendations for midazolam in total intravenous anaesthesia techniques are possible, aiming at hypnotic plasma concentrations of at least 250 ng.ml^-1. Due to its biological half-life of 150–180 min and interindividual differences in drug susceptibility, prolonged recovery periods have been observed that can safely and reliably be antagonised by flumazenil, if necessary. It is recommended that flumazenil be administered carefully by titration in increments of 0.1 mg.min^-1 to avoid emergence reactions by awakening too fast (tachycardia, hypertension). Usually a mean total dose of 0.4–0.5 mg will lead to prompt awakening.     

The role of midazolam and flumazenil in urology

The effects of midazolam (3–10 mg im.) and their reversal by flumazenil were studied in transurethral endoscopic procedures performed using topical analgesia. In one randomised study, patients (n = 84) received either no medication or flumazenil (0.5 mg i.v.) on completion of endoscopy. Recovery was assessed subjectively. Within 15 min, 83% of those receiving flumazenil were considered ready for discharge compared with only 24% of the control group ( P <0.001). In a second randomised, double-blind, placebo-controlled trial of 44 patients, post-operative recovery was assessed using five objective psychomotor tests. Whereas the placebo group took up to 2 h to recover, those receiving flumazenil recovered fully or returned to near control values within 15 min. Sedoanalgesia - a technique combining adequate local anaesthesia with sedation (using midazolam) - has wide application in urology, and the introduction of flumazenil has major implications for the practice of day-case surgery.     

Midazolam-flumazenil versus propofol anaesthesia for scoliosis surgery with wake-up tests

Background : Wake-up tests may be necessary during scoliosis surgery to ensure that spinal function remains intact.
Methods : Intra- and postoperative wake-up tests were performed together with somatosensory cortical evoked potentials (SCEPs) monitoring in 40 patients randomized to either midazolam (M) or propofol (P) infusions for scoliosis surgery. Other anaesthetic medication was similar in both groups. At the surgeon's request, N₂O was turned off and midazolam or propofol infusions were discontinued. In the M group, flumazenil was given in refracted doses. Patients were asked to move hands and feet. The test was repeated immediately after the end of surgery.
Results : The median intraoperative wake-up times were 2.9 min in the M group and 16.0 min in the P group. The respective postoperative wake-up times were 1.8 and 13.9 min. The quality of both intra- and postoperative arousals was significantly better in the M group. Twelve patients in the P group could not be awakened intraoperatively within 15 min and were given nalox-one. One of these patients woke up violently and dislodged the endotracheal tube. Another patient in the P group had explicit recall of the test, but no pain. Five patients in the M group became resedated in the recovery room. Cost of anaesthetic drugs was similar in both groups. Satisfactory intraoperative SCEPs were recorded from 17 patients in each group. There were no neurological sequelae.
Conclusions : Wake-up tests can be conducted faster and better with midazolam-flumazenil sequence compared with propofol.     

Comparison of the recovery characteristics of midazolam, alone or antagonised with flumazenil, and thiopental in ASA III-IV patients

Sixty non-premedicated male patients, physically ASA III-IV, 50–80 years of age, undergoing translumbar aor-thography, were randomly allocated into three groups. Group A received midazolam (0.13 mg·kg^-1), group B received thiopental (4 mg · kg^-1), and group C midazolam (0.13 mg · kg^-1) combined with flumazenil (6 μg · kg^-1) at the end of the operation. Three minutes before the anaesthesia began, fentanyl (1.5 μg · kg^-1) was administered to all the patients. An evaluation was made of the time they took to open their eyes spontaneously, of time-space orientation, comprehension-collaboration, hypnosedation, psychomotor performance and memory. In groups "C" and "B" spontaneous opening of the eyes took place before that of group "A". The recovery of orientation, comprehension and hypnosedation was fastest with thiopental, next with midazolam combined with flumazenil, and later with midazolam. Psychomotor performance in Trieger test was impaired for a shorter period with thiopental than in the other two groups. Recovery in group "C" was incomplete within the time, with the result that resedation was detected in 20% of the subjects.     

The use of midazolam and flumazenil in locoregional anaesthesia: an overview

Midazolam is useful as an intravenous supplement to local anaesthesia techniques in producing sedation, amnesia and anxiolysis, and has about five times the sedative potency of diazepam. Considerable interpatient variability exists in dose requirements, especially in elderly patients. The combined effects of local anaesthetics and midazolam may contribute to enhanced haemodynamic effects and changes in the respiratory pattern, impairing ventilation and oxygenation. Flumazenil can be titrated in incremental doses to reverse the residual sedative effects of midazolam, without intrinsic haemodynamic or respiratory effects, but may not fully antagonise the decrease in chemoreceptor sensitivity nor the changes in breathing pattern induced by midazolam. Patients treated with epidural or spinal anaesthesia supplemented with midazolam should be monitored to avoid hypoxaemia risks even after the administration of flumazenil.     

Midazolam and flumazenil pharmacokinetics and pharmacodynamics following simultaneous administration to human volunteers

Resedation after antagonism of midazolam sedation with flumazenil may occur because some individuals have rapid elimination of flumazenil but slow elimination of midazolam. To determine whether there are parallel or divergent rates of elimination of the two drugs between individuals, the pharmacokinetic profiles of midazolam and flumazenil were studied simultaneously in 12 adult male volunteers. Free drug concentration data for the two drugs were incorporated into a receptor occupancy model and psychomotor testing was performed and correlated with receptor occupancy. Variation was found between individuals in the pharmacokinetics of the two drugs. There were significant correlations between Cl_tot, ( P < 0.01) but not in t_1/2a, t_1/2b, V_c, or VD_st. In individuals, midazolam elimination half–life ranged from less than half that of flumazenil to more than three times that of flumazenil. There was a relatively poor, although statistically significant linear correlation found between calculated receptor occupancy and critical flicker fusion frequency, r = 0.50, P <0.01, and linear analogue scales of sedation r = 0.56, P <0.005; and anxiolysis, r = 0.54, P < 0.005. There is divergence in the disposition and elimination of midazolam and flumazenil in some individuals. A benzodiazepine receptor occupancy model is useful for predicting the consequent differences in clinical effect when the drugs are given together.     

Midazolam sedation and local anaesthesia compared with general anaesthesia for paediatric outpatient dental surgery

Midazolam sedation may offer an alternative to general anaesthesia for dental treatment in children. This study evaluated the efficacy and safety of i.v. midazolam with local anaesthesia in uncooperative paediatric dental patients. Thirty children (aged 2–10 years, physical status ASA 1 or 2) were randomized into two groups to receive general anaesthesia (group G) or local anaesthesia during sedation with i.v. midazolam (group M). Incremental doses of midazolam 0.05 mgkg^-1 were given to a sedative endpoint of 2 on a Sedation Scale of 5–0 (hyperactive–asleep), or 0.4 mgkg^-1 maximum, then as needed to maintain the same level of sedation. Amnesia was tested at the sedative endpoint by showing the child a tinkling ball and checking recall 1 h after surgery. Recovery was assessed by the Post-Anesthetic Recovery Scale at 3 h (0–10) with 10 representing readiness for discharge. Questionnaires were completed by the dentist and anaesthetist during recovery and by telephone to the parents 1–2 weeks later. Dental treatment was completed according to protocol in 11 of the 15 patients in group M (sedative doses: 0.27 0.09 mgkg^-1, mean SD) and all patients in group G. Recovery was similar in both groups, with discharge criteria met after 1 h 30 min in all but one group M patient. None had recall for intra-operative events. However, the variability of responsiveness makes midazolam unreliable when used alone to facilitate dental treatment, and the high dose requirements make close monitoring of paediatric patients mandatory.     

A review of recovery from sevoflurane anaesthesia: comparisons with isoflurane and propofol including meta-analysis

BACKGROUND: Sevoflurane has a lower blood:gas partition coefficient than isoflurane and thus should be associated with a more rapid recovery from anaesthesia. METHODS: A review and meta-analysis were employed to examine the recovery profiles of adult patients following anaesthesia, comparing sevoflurane to isoflurane and sevoflurane to propofol. RESULTS: There were significant differences in times to several recovery events that favoured sevoflurane to isoflurane anaesthesia, including time to emergence, response to commands, extubation, and orientation. Likewise, there were significant differences in times to the same recovery events following anaesthesia with sevoflurane versus propofol. There were no differences in time to recovery room discharge when comparing sevoflurane to isoflurane or propofol. CONCLUSION: The observed differences between sevoflurane and isoflurane or propofol anaesthesia support the postulate that the use of sevoflurane is associated with a more rapid recovery from anaesthesia than either isoflurane or propofol.     

Buprenorphine antagonism of ventilatory depression following fentanyl anaesthesia

In order to compare the effect of buprenorphine and naloxone on respiratory depression after fentanyl anaesthesia (25 micrograms/kg), 32 women scheduled for elective abdominal hysterectomy participated in a double-blind randomized investigation. At termination of anaesthesia, after antagonizing residual neuromuscular blockade, 20 normocapnic patients with a respiratory rate of 4 breaths/min or less entered the study, receiving either buprenorphine (0.6 mg in 20 ml NaCl) or naloxone (0.4 mg in 20 ml NaCl) 2 ml/min until 20 ml was given or until the respiratory rate exceeded 8 breaths/min. Respiratory rate, PaCO2, sedation score, and pain intensity were evaluated during a 3-h study period. Fifteen min after beginning the treatment, all the patients in both groups had their ventilatory depression antagonized. There were no statistically significant differences in respiratory rates between groups except at 15 min. On no occasion did either PaCO2 or a sedation score differ statistically significantly between the groups. At 15 min all patients in the buprenorphine group had no or mild pain, compared to the patients in the naloxone group, of whom 50% had moderate to severe pain (P less than 0.05). It seems as if buprenorphine is as effective as naloxone in antagonizing respiratory rate depression following fentanyl anaesthesia.     

Recovery characteristics of sevoflurane or halothane for day-case anaesthesia in children aged 1-3 years

BACKGROUND: Our objective was to compare the recovery characteristics of sevoflurane and halothane for short day-case anaesthesia in a specifically limited age group of children 1-3 yr. METHODS: Eighty unpremedicated children undergoing day-case adenoidectomy were randomly assigned to receive inhalational induction with either sevoflurane 8% or halothane 5% and nitrous oxide in oxygen (70/30) via a face mask. Tracheal intubation was performed without a muscle relaxant. Anaesthesia was continued with the volatile anaesthetic, adjusted to maintain heart rate and blood pressure within +/-20% of initial values. Recovery was evaluated using a modified Aldrete score, a Pain/Discomfort scale and by measuring recovery end-points. A postoperative questionnaire was used to determine the well-being of the child at home until 24 h after discharge. RESULTS: Emergence and interaction occurred significantly earlier after sevoflurane than halothane but discharge times were similar. More children in the sevoflurane group achieved full Aldrete scores within the first 30 min after anaesthesia, although this group suffered more discomfort during the first 10 min. The amount of postoperative analgesic administered was higher and the first dose given earlier in the sevoflurane group. Postoperative vomiting was more common with halothane, but side-effects in the two groups were otherwise similar in the recovery room and at home. CONCLUSIONS: In children 1-3 yr, sevoflurane provided more rapid early recovery but not discharge after anaesthesia of <30-min duration. Apart from more vomiting with halothane and more discomfort during the first 10 min after awakening with sevoflurane, the quality of recovery was similar with the two anaesthestics.     

Propofol–nitrous oxide versus thiopentone–isoflurane–nitrous oxide anaesthesia for uvulopalatopharyngoplasty in patients with sleep apnea

A randomized prospective study was performed to compare the recovery in 41 patients undergoing uvulopalatopharyngoplasty (UPPP) with either propofol-nitrous oxide-fentanyl or thiopentone-isoflurane-nitrous oxide-fentanyl anaesthesia. The patients were referred to UPPP after examination including polysomnography and otorhinolaryngological examination. The propofol group received propofol 2 mg·kg^-1 for induction followed by an infusion of 10 mg·kg^-1·h^-1 after intubation. The thiopentone-isofiurane group received 5 mg·kg^-1 of thiopentone for induction followed by isoflurane (0.5–2%) after intubation. Other medication was similar in both groups. In the propofol group the patients had a significantly better oxygen saturation during the first postoperative hour ( P < 0.05), and a higher rate of breathing ( P < 0.05), indicating a more rapid recovery of the physiologic control of breathing. Pain as measured by visual analogue score was lower ( P < 0.05) during the second postoperative hour compared with the isoflurane group. Apneic episodes occurred with similar frequency in both groups, and they were related to the severity of obstructive sleep apnea (OSA). We conclude that propofol is preferable to thiopentone-isofiurane in UPPP operations, because physiologic respiratory control recovers faster and postoperative pain is less intense.