Propofol auto-co-induction as an alternative to midazolam co-induction for ambulatory surgery

We propose the use of an intravenous propofol/propofol auto-co-induction technique as an alternative to propofol/midazolam for induction of anaesthesia. We have studied 54 unpremedicated ASA 1 or 2 patients undergoing day-stay anaesthesia for minor orthopaedic surgery. All received 10 micrograms.kg-1 or alfentanil before induction, followed by either midazolam 0.05 mg.kg-1, propofol 0.4 mg.kg-1 or saline, and 2 min later, a propofol infusion at a rate of 50 mg.kg-1.h-1 until loss of eyelash reflex. We compared pre- and postinduction haemodynamic changes, complications at insertion of a laryngeal mask airway and recovery from anaesthesia in the three groups. Both co-induction techniques showed less postinduction hypotension and significant reduction of the total induction dose of propofol when compared to the control group. In the propofol/propofol group there was a decreased incidence of apnoea during induction of anaesthesia. These patients were discharged from hospital 2 h after the end of anaesthesia whereas patients in the midazolam/propofol group were discharged after 2 1/2 h (p < 0.001).     

Midazolam coinduction does not delay discharge after very brief propofol anaesthesia

Previous reports have demonstrated synergism of midazolam and propofol for induction of anaesthesia in humans. We tested the hypothesis that in the presence of alfentanil, the combination of midazolam with propofol for a very brief operative procedure would not affect the recovery phase. During pre-oxygenation, 64 outpatients scheduled for dilatation and curettage received placebo, or low-dose midazolam (0.03 mg · kg^?1), or high-dose midazolam (0.06 mg · kg^?1) iv, in a randomized double-blind manner. They then received alfentanil 10 μg · kg^?1 iv, followed by titrated doses of propofol iv for induction and maintenance of anaesthesia. Ventilation with 70% N₂O in O₂ by mask was controlled to achieve a PETCO₂ 30–40 mmHg. Outcome measures were: propofol dose (induction and maintenance), time until eye-opening to command, and time to discharge-readiness. Propofol induction dose was decreased by increasing doses of midazolam (P = 0.00005). Midazolam delayed time to eye-opening (P = 0.02) but not time to discharge-readiness. This study had an 80% power to detect a 39 min difference in time to discharge-readiness. We conclude that midazolam propofol co-induction in the presence of alfentanil delays eye-opening, but does not delay discharge after anaesthesia.     

Cognitive and psychomotor performance following isoflurane, midazolam/alfentanil and propofol anesthesia. A comparative study]

Mental and psychomotor abilities are impaired to varying degrees after general anaesthesia. This has important implications for the time over which patients are monitored in the recovery room and for the discharge of outpatients after day surgery. The present study was undertaken to compare recovery and mental and psychomotor skills in the first 60 min following general anaesthesia with isoflurane, midazolam/alfentanil and propofol. METHODS. A total of 45 patients undergoing microsurgical lumbar nucleotomy were randomized to three study groups. Group 1 (n = 15): anaesthesia was induced with thiopentone and maintained with isoflurane; group 2 (n = 15): anaesthesia was induced with midazolam and maintained with alfentanil; group 3 (n = 15): anaesthesia was induced and maintained with propofol. Vecuronium was used for muscle relaxation and the lungs were ventilated with a mixture of 66% nitrous oxide in oxygen. The following were checked 15, 30, 45, and 60 min after extubation: choice reaction times and critical flicker fusion for psychomotor testing; the maze test and a modification of the ball-bearing test for discrimination of motor and mental activities; and short- and long-term memory. RESULTS. Immediate recovery did not differ in the three different groups. In all patients psychomotor function was impaired compared with baseline for more than 60 min after general anaesthesia. However, impairment was significantly less pronounced after propofol, and recovery to preanaesthesia values was faster following propofol than after midazolam/alfentanil, and slowest after isoflurane-anaesthesia (Figs. 1, 2). The flicker fusion frequency, a very sensitive parameter for the persisting effects of anaesthetics, was significantly higher following propofol anaesthesia and remained so throughout the entire study period (Fig. 3). By 30 min after extubation, short-term memory was already normal in patients who had undergone propofol anaesthesia, and a statistically significant difference from the midazolam/alfentanil and isoflurane anaesthesia groups was obvious throughout the entire study period. However, no differences in long-term memory were found. At 30 min after propofol anaesthesia all patients were able to perform the ball-bearing test, as against 13 patients following midazolam/alfentanil and 10 patients following isoflurane (Table 3). The maze test was mostly impaired after midazolam/alfentanil anaesthesia. Patients who underwent isoflurane anaesthesia needed the same time for the maze test at 60 min afterwards propofol patients needed after 30 min (Table 2). Side effects, e.g., nausea, vomiting, and double vision, were observed significantly more often in groups 1 and 2 (Table 4). DISCUSSION AND CONCLUSION. The results indicate that in operations of approximately 90 min duration the return of motor and mental abilities is faster following propofol anaesthesia. At 30 min after extubation following propofol anaesthesia patients had test results that allow their transfer from the recovery room, while it took 60 min for patients in the two other groups to reach the same levels of motor and mental function. This is important for the duration of monitoring in the recovery room and, especially, for day case anaesthesia.     

Co-induction and laryngeal mask insertion# A comparison of thiopentone versus propofol

Conditions for insertion of the laryngeal mask airway were assessed in 70 unpremedicated patients comparing the co-induction with midazolam-alfentanil-thiopentone and midazolam–alfentanil–propofol. Following pre-induction doses of midazolam 0.04 mg.kg⁻¹ and alfentanil 10 μg.kg⁻¹, patients received equipotent doses of either thiopentone or propofol. Whilst jaw relaxation and ease of laryngeal mask insertion were similar between the two groups, patients receiving propofol were less likely to have undesired responses requiring additional boluses of induction agent (p < 0.05). We conclude that, using these doses, propofol is superior to thiopentone for laryngeal mask airway insertion when using a co-induction technique.     

A comparison between midazolam co-induction and propofol predosing for the induction of anaesthesia in the elderly

In a prospective, double-blind, randomised, placebo-controlled trial, we have compared the effects of midazolam co-induction with propofol predosing on the induction dose requirements of propofol in elderly patients. We enrolled 60 patients aged > 70 years, attending for urological surgery. The patients were allocated randomly to one of three groups, to receive either midazolam 0.02 mg.kg(-1), propofol 0.25 mg.kg(-1), or normal saline 2 ml (placebo) 2 min prior to induction of anaesthesia using propofol 1% infusion at 300 ml.h(-1). The propofol dose requirements for induction were recorded for two end-points (loss of verbal contact and insertion of an oropharyngeal airway). Cardiovascular parameters were recorded at 1-min intervals for each patient until induction was complete. The midazolam group showed a significant reduction in propofol dose requirements for induction (p = 0.05) compared to the placebo group. The propofol group did not show a significant dose reduction compared to placebo. There were no demonstrable differences in terms of improved cardiovascular stability between groups. We conclude that propofol predosing does not significantly reduce the induction dose of propofol required in the elderly, and there were no cardiovascular benefits to either midazolam co-induction or propofol predosing in the elderly.     

Total intravenous anaesthesia for laparoscopy

Two techniques of total intravenous anaesthesia for laparoscopy were compared in 80 patients. Group 1 received alfentanil, propofol and vecuronium, and Group 2 alfentanil, midazolam, ketamine and vecuronium. Haemodynamic stability after induction and the pressor response to tracheal intubation were significantly different. There was no significant difference in recovery times between the two groups and little difference in other postoperative sequelae.     

A comparison of two anaesthetic techniques for daycase arthroscopy

A randomised, double-blind study of 100 patients admitted for daycase arthroscopy was undertaken. Fifty patients received alfentanil 500 micrograms and midazolam 5 mg, and 50 received alfentanil 500 micrograms alone, in each case 2 minutes before induction of anaesthesia with methohexitone. Anaesthesia was maintained in both groups with nitrous oxide, oxygen and enflurane. Recovery was assessed quantitatively by measuring time to when they awoke and by a comparison of pre- and postoperative performance of p-deletion and postbox tests. Qualitative assessment of recovery and of postoperative pain was also undertaken. Patients completed a questionnaire to record the incidence of any anaesthetic-related symptoms on the first and second postoperative days. Patients who received midazolam required a reduced dose of methohexitone but their initial recovery time was prolonged significantly. The incidences of anaesthetic-related side effects and postoperative pain were similar in the two groups and while the questionnaires did not reveal any statistically significant differences in symptoms on the first 2 postoperative days, the results indicated that patients who received a larger induction dose of methohexitone were subjectively drowsier on the first day after operation.     

A comparison of midazolam co-induction with propofol predosing for induction of anaesthesia

In a double-blind, placebo-controlled study of 90 ASA 1 and 2 patients scheduled for elective surgery we compared the effect of pre-administering midazolam 2 mg or propofol 30 mg on the dose of propofol subsequently required to induce anaesthesia. Using loss of response to verbal command and tolerance to placement of a facemask as end-points, the dose of propofol required to induce anaesthesia was significantly smaller in the patients given propofol (1.87 mg.kg-1) or midazolam (1.71 mg.kg-1) when compared to the control group (2.38 mg.kg-1). Although the decrease in blood pressure following induction was no difference between the two study groups and the decrease was felt not to be of clinical significance in this group of patients. As propofol is presented ' ... for use in a single patient only' and the technique of predosing with propofol allowed induction of all patients with less than 200 mg (a single ampoule), we question on a cost basis whether midazolam co-induction is necessary to reduce propofol induction doses.     

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.     

Target-controlled propofol requirements at induction of anaesthesia: effect of remifentanil and midazolam

BACKGROUND AND OBJECTIVE: Target-controlled infusions of anaesthetic agents have become increasingly available. They can involve the use of propofol in combination with an opioid or a benzodiazepine. The effect site concentration of propofol infusions has been advocated as a method of estimating drug distribution. We investigated the influence of co-induction with remifentanil and midazolam on effect site propofol requirements at induction of anaesthesia using target-controlled infusions. METHODS: Sixty-six consenting adult patients were randomly allocated to three treatment groups. Each group received induction of anaesthesia with a different total intravenous technique. One group was induced with target-controlled propofol alone; another received target-controlled propofol and target-controlled remifentanil (3 ng mL-1); and the last received midazolam (0.03 mg kg-1), target-controlled remifentanil (3 ng mL-1) and target-controlled propofol. Computer simulation was used to calculate effect site concentrations. We recorded propofol dose and effect site concentration at loss of verbal response. RESULTS: The effect site concentration (Ce50) of propofol alone was 2.19 micrograms mL-1. This was reduced to 1.55 micrograms mL-1 during co-induction with remifentanil and further reduced to 0.64 microgram mL-1 with midazolam premedication (P < 0.001; ANOVA). CONCLUSIONS: We conclude that co-induction with remifentanil alone or with midazolam can be used to reduce propofol doses at induction of anaesthesia using target-controlled infusions. We believe that using effect site concentration may prove a useful tool in routine clinical practice.     

Alfentanil used to supplement propofol infusions for oesophagoscopy and bronchoscopy

This randomised double-blinded study compared the cardiovascular stability and rate of recovery when propofol infusions with or without alfentanil were used to provide anaesthesia for rigid oesophagoscopy and (or) bronchoscopy. Forty-six patients were allocated randomly to receive either alfentanil 10 micrograms/kg or saline just before a rapid sequence induction with propofol. Suxamethonium 1 mg/kg was given and infusions of suxamethonium 10 mg/minute and propofol (10 mg/kg/hour for 10 minutes, 8 mg/kg/hour for 10 minutes and then 6 mg/kg/hour thereafter) were started. There were 23 patients in each group with no significant demographic differences between the groups. A significantly mean lower induction dose of propofol was needed in the alfentanil group (1.7 mg/kg compared to 2.2 mg/kg). Cardiovascular measurements were made on the ward pre-operatively, just before induction, just after induction, just after intubation, and at 3-minute intervals thereafter. Arterial pressure was significantly lower during the procedure in the patients who received alfentanil and there was a significant incidence of hypotension. There was no significant difference between the groups in respect of heart rate, with a significant increase in both groups just after intubation compared to the baseline values. Recovery from anaesthesia was assessed using the critical flicker fusion threshold. No differences were found between the groups and patients in both groups had returned to baseline values by 60 minutes. No patient had any recall of intra-operative events, and there were no other adverse effects of any significance.     

The influence of esmolol on the dose of propofol required for induction of anaesthesia

Cardiac output may be an important determinant of the induction dose of intravenous anaesthetic. Esmolol is known to reduce cardiac output, and we examined its effect on the propofol dose required for induction of anaesthesia. The size of the effect seen with esmolol was compared with midazolam co-induction. Sixty patients were randomly allocated to placebo (saline), esmolol (1mg x kg(-1) bolus, followed by an infusion at 250 microg x kg(-1)min(-1)) or midazolam (0.04 mg x kg(-1)) groups. Induction of anaesthesia commenced 3 min following the administration of the study drug, using a Diprifusor set to achieve plasma propofol concentrations of 10 microg x ml(-1) at 5 min. The primary end point used was the propofol dose per kg at loss of response to command. The mean (SD) propofol dose for each group was 2.38 (0.48) mg x kg(-1) for placebo, 1.79 (0.36) mg x kg(-1) for esmolol and 1.34 (0.35) mg x kg(-1) for midazolam (all means significantly different; p < 0.0005). We found that predosing with esmolol reduces the propofol requirements for induction of anaesthesia by 25%.     

Comparison of midazolam and propofol in combination with alfentanil for total intravenous anesthesia

Hemodynamic function during induction of anesthesia, the alfentanil and naloxone requirements, and the speed of recovery from total intravenous anesthesia with alfentanil/midazolam (group M, n = 10) or alfentanil/propofol (group P, n = 10) were compared in patients undergoing lower limb surgery. Twenty patients were randomly assigned to receive either 2 mg/kg propofol in 5 min followed by 9 mg.kg-1.h-1 for 30 min and 4.5 mg.kg-1.h-1 until skin closure, or 0.42 mg/kg midazolam in 5 min followed by 0.125 mg.kg-1.h-1 until skin closure. Simultaneously, a variable-rate infusion of alfentanil was given. Patients were ventilated with 30% oxygen in air. In both groups blood pressure and heart rate decreased significantly (P less than 0.02) and to a similar extent during induction. The total dose of alfentanil was similar in both groups. No patient in group P and nine patients in group M needed naloxone (average dose 130 +/- 70 micrograms, P less than 0.001). Recovery, as judged by psychomotor tests (90% score was reached at 1 h in the P group and at about 4 h in the M group, P less than 0.001), sedative scores, and orientation in time and place, was shorter in group P than in group M. The conclusion is reached that propofol is superior to midazolam in total intravenous anesthesia with alfentanil.     

Ambulatory anesthesia and induced abortion. Comparative study of propofol-alfentanyl and ketamine-midazolam combinations

The use of propofol alone or with alfentanil in the day-case anaesthesia for abortion was compared with that of ketamine with midazolam. Two hundred young women were assigned to two successive series of two groups each. The four groups were: group 1 (2 mg . kg-1 propofol only); group II (0.5 mg . kg-1 ketamine with 0.25 mg . kg-1 midazolam); group III (2 mg . kg-1 propofol with 4 micrograms . kg-1 alfentanil); group IV (1 mg . kg-1 ketamine with 0.1 mg . kg-1 midazolam). All the patients were premedicated one hour before anaesthesia with 0.25 mg . kg-1 midazolam orally. All the patients were asleep at the end of the propofol injection (60 s), and 10 to 15 s later for the ketamine-midazolam groups. The haemodynamic parameters did not vary much during induction with ketamine-midazolam. In the propofol groups, the heart rate remained steady, with an 8 to 12% fall in blood pressure. A fall of the mandible was seen in 40 and 84% of the patients in the propofol groups, with a short apnoea in 32 and 48% of these same patients. Clinical recovery was very quick, less than 12 min for all groups. The four psychomotor and sensory tests were carried out at the 30th min by 95% of the patients in the propofol groups, whereas only 50% of those in the ketamine-midazolam groups did so. Speed and quality were significantly better in the propofol groups. The most frequent adverse effect of propofol was pain during injection in 32 and 14% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of alfentanil pre-treatment on ventilatory effects of doxapram following induction of anaesthesia with propofol

Background : Hypoventilation may occur following induction of anaesthesia with propofol and is potentiated by concurrent use of opioid drugs. This effect is undesirable in patients who will continue to maintain spontaneous respiration during anaesthesia and surgery. The analeptic drug doxapram is known to have selective respiratory stimulatory effects but its action during induction of anaesthesia has been inconsistent.
Method : In a double-blind, placebo-controlled study, the influence of alfentanil pre-treatment on the ventilatory effects of doxapram given during induction of anaesthesia with propofol was studied in 40 patients. Four groups of ten patients (two groups pre-treated with 7 μg·kg^-1 of alfentanil and two groups with saline) were randomly allocated to receive either 0.5 mg·kg^-1doxapram or saline following infusion of propofol to loss of verbal contact.
Results : In the groups that received doxapram, minute volumes were significantly increased and end-tidal carbon dioxide concentrations were significantly reduced compared to control groups, although the duration and extent of these effects were less in the group that received alfentanil. Doxapram also reversed an alfentanil-induced reduction in respiratory rate. No adverse cardiovascular or neurological stimulatory effects of doxapram were evident at any time.
Conclusion : We conclude that doxapram 0.5 mg·kg^-1 is effective in augmenting ventilation that has been obtunded following induction of anaesthesia with propofol in patients pre-treated with alfentanil.     

Midazolam and awareness with recall during total intravenous anaesthesia

Purpose  

A double-blind study was undertaken to evaluate the influence of graded doses of midazolam on propofol infusion requirements, recovery characteristics and the quality of recovery, associated with propofol/alfentanil/O₂ total intravenous anaesthesia (TIVA).     

Induction and recovery characteristics of desflurane in day case patients: A comparison with propofol

Desflurane is an ether halogenated exclusively with fluorine. It has a blood/gas partition coefficient of 0.42 (cf. isoflurane 1.40 and nitrous oxide 0.46). This characteristic suggests that it should provide both a fast induction of anaesthesia and a rapid recovery from anaesthesia. To assess this, 60 patients were entered into a study and allocated at random to one of four groups receiving either desflurane or propofol for induction and maintenance of anaesthesia. Desflurane caused loss of consciousness in approximately 2 minutes during gaseous inductions. The psychomotor scores in the patients who received propofol for induction and maintenance of anaesthesia were significantly worse compared with those who were given desflurane for either induction and maintenance or for maintenance only. There was also a tendency for other recovery parameters to be faster in the patients receiving desflurane although this did not reach statistical significance. This suggests that desflurane would be a suitable agent for day case anaesthesia providing for a rapid recovery.     

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.     

Patient-controlled drug administration during local anesthesia: A comparison of midazolam, propofol, and alfentanil

Study Objective: To evaluate the perioperative effects of alfentanil, midazolam, and propofol when administered using a patient-controlled analgesia (PCA) device during local anesthesia.

Design: Randomized, single-blind comparative study.

Setting: Outpatient surgery center at a university teaching hospital.

Patients: Ninety outpatients undergoing minor elective surgical procedures with local anesthetic infiltration were assigned to one of three treatment groups.

Interventions: After premedication with midazolam 1 mg intravenously (IV) and fentanyl 50 μg IV, patients were allowed to self-administer 2 ml bolus doses of either alfentanil 250 μg/ml, midazolam 0.4 mg/ml, or propofol 10 mg/ml at minimal intervals of 3 minutes to supplement a basal infusion rate of 5 ml/hr.

Measurements and Main Results: The total intraoperative dosages of alfentanil, midazolam, and propofol were 2.7 ± 1.1 mg, 4.7 ± 2.7 mg, and 114 ± 42 mg, respectively, for procedures lasting 48 ± 28 minutes to 51 ± 19 minutes (means ± SD). Propofol produced more pain on injection (39% vs. 4% and 6% in the alfentanil and midazolam groups, respectively). Episodes of arterial oxygen saturation less than 90% were more frequent with alfentanil (28%) than with midazolam (3%) or propofol (13%). Using the visual analog scale, patients reported comparable levels of discomfort, anxiety, and sedation during the operation in all three treatment groups. Postoperative picture recall was significantly decreased with midazolam versus alfentanil and propofol. Finally, postoperative nausea was reported more frequently in the alfentanil group (29%) than in the midazolam (10%) or propofol (18%) groups, contributing to a significant prolongation of the discharge time in the alfentanil-treated patients.

Conclusions: When self-administered as adjuvants during local anesthesia using a PCA delivery system, alfentanil, midazolam, and propofol were equally acceptable to patients. However, propofol and midazolam were associated with fewer perioperative complications than was alfentanil.     

Alfentanil in daycase anaesthesia

The effect of the addition of a single dose of 7 μg.kg⁻¹ of alfentanil to a propofol/enflurane anaesthetic on the quality of anaesthesia and recovery was assessed. A total of 53 ASA grade 1 or 2 patients who underwent daycase dental surgery were allocated randomly to receive either alfentanil or saline. The study was blinded so that neither the anaesthetist nor the assessor was aware of which solution had been given. Patients in the alfentanil group took signficantly longer to recommence spontaneous ventilation (p = 0.035). Both techniques provided good quality of anaesthesia. Postoperative morbidity was common (45% of patients), but there was no difference between the groups. The rate of recovery was similar in the two groups and no patient required hospital admission after the final assessment at 3 h. Drowsiness was only mild to moderate in both groups at 24 h. A single dose of alfentanil can be administered safely as part of a daycase anaesthetic without increasing morbidity, although there appears to be little advantage in doing so.