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Midazolam reduces the dose of propofol required for induction of anaesthesia and laryngeal mask airway insertion

Gill, P. S.; Shah, J.; Ogilvy, A.

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European Journal of Anaesthesiology: March 2001 - Volume 18 - Issue 3 - p 166-170

Abstract

Introduction

Insertion of the laryngeal mask airway in the anaesthetized patient can sometimes be difficult, usually because of inadequate jaw opening, coughing or gagging. Propofol has been advocated as the anaesthetic induction agent of choice if a laryngeal mask is used because of its depressant effect on laryngeal reflexes compared with other intravenous (i.v.) anaesthetics [1,2]. However, when used as the sole induction agent, relatively large doses of propofol are required to achieve successful laryngeal mask insertion [3]. This has cost implications and may produce unwanted cardiorespiratory depression.

Co-induction’, is a technique using a small dose of hypnotic agent to augment induction with another intravenous anaesthetic agent [4]. Recently, several studies have examined co-induction techniques on the conditions for laryngeal mask insertion using combinations of rapid acting opioids or midazolam combined with thiopental or propofol [5–9]. Co-induction with propofol, midazolam and alfentanil has been shown to reduce propofol requirements and provides better conditions for laryngeal mask insertion compared with induction with propofol and alfentanil alone [6]. Midazolam reduces propofol requirements for the insertion of a laryngeal mask when used without opioids in both adults and [8] and children [9].

Other studies have investigated lidocaine on its effect on conditions for laryngeal mask insertion. Intravenous lidocaine given prior to induction has also been shown to improve conditions for laryngeal mask insertion but does not reduce propofol requirements [10].

Thus, it can be seen that a number of various co-induction agents have been used to assist insertion of the laryngeal mask airway. The aim of this study was to establish which co-induction agents provide better conditions for laryngeal mask airway insertion. We compared lidocaine and midazolam, either alone or in combination, as co-induction agents for inducing anaesthesia and insertion of the laryngeal mask with propofol and fentanyl. This to our knowledge has not been previously described.

Methods

This was a randomized, prospective double-blind study that had the approval of the local Ethics Committee. One hundred and forty-two ASA I or II patients aged between 18 and 65 years presenting for elective minor surgery in whom a laryngeal mask was an appropriate part of their anaesthetic were recruited in the study. No patient received premedication with any sedative action or was receiving regular sedative medication. Patients with gastro-oesophageal reflux, reactive airways disease, untreated hypertension and obesity (> 30% above ideal body weight) were excluded. When the patient arrived in the anaesthetic room standard monitoring, consisting of electrocardiography, non-invasive pressure and pulse oximetry was applied. Each patient was randomly allocated to one of four induction regimens using a sealed envelope. Midazolam, lidocaine or a placebo was drawn up by a second anaesthetist on a dose per bodyweight basis. The anaesthetist inserting the laryngeal mask (J. S. only) was blinded to the contents of the study drugs. The laryngeal mask airway was inserted using the method described by Brimacombe and Brain [11]. Induction consisted of one of the following regimens.

Group 1

Patients were injected with normal saline, NaCl 0.9% (midazolam placebo) and fentanyl 1 µg kg−1 followed after 2 min by lidocaine 1.5 mg kg−1 over 30 s. One minute later, propofol 1% was infused at 3.3 mL min−1 using a Graseby 3200 infusion pump until the patient did not respond to command. At this point the infusion was stopped and 30 s later laryngeal mask insertion was attempted.

Group 2

Patients were injected with midazolam 0.04 mg kg−1 and fentanyl 1 µg kg−1 followed after 2 min with saline 0.9% (lidocaine placebo) over 30 s followed by the standard propofol induction and laryngeal mask insertion.

Group 3

Patients received i.v. midazolam 0.04 mg kg−1 and fentanyl 1µ kg−1 followed after 2 min with lidocaine 1.5 mg over 30 s followed by the standard propofol induction and laryngeal mask insertion.

Group 4

Patients received i.v. 0.9% NaCl (midazolam placebo) and fentanyl 1 µg kg−1 followed after 2 min by 0.9% NaCl (lidocaine placebo) followed by the standard propofol induction and laryngeal mask insertion.

If laryngeal mask insertion proved to be impossible due to inadequate jaw relaxation, or if the patient did not tolerate the laryngeal mask due to coughing or gagging, further boluses of propofol 0.25 mg kg−1 were given every 30 s until insertion was successful. Patients were asked at the time of induction whether they were experiencing any pain with the injection of propofol. After insertion of the laryngeal mask, the patient breathed 2% isoflurane in oxygen 30% and nitrous oxide 70%. Assisted ventilation was continued at a rate to maintain end-tidal carbon dioxide between 4.5 and 6% until spontaneous ventilation commenced. This was the end point of the study.

Data analysis

The following variables were recorded: patient demographics, age, gender, body mass index, smoking status and ASA grade. Total propofol dose required for successful insertion of the laryngeal mask and the incidence of pain on injection was noted. Jaw opening was graded as full, partial or none, and the ease of laryngeal mask insertion was graded as easy or difficult. An easy insertion was defined as one that was performed as a single swift manoeuvre and was not met with any resistance. A difficult insertion involved either two or more attempts at insertion or repositioning of the laryngeal mask.

Analysis of Variance (ANOVA) and Kruskal–Wallis tests were used to compare parametric and non-parametric variables, respectively, between the four groups. Nominal data were compared using χ2- and Fisher's tests.

Results

Patients were equally matched in respect of age, gender, body mass index and smoking status (Table 1). Groups 2 and 3 required a significantly lower dose of propofol to induce anaesthesia and insert a laryngeal mask, P < 0.001 (Table 2). There was no difference in the number of patients needing additional boluses of propofol to achieve laryngeal mask insertion (Table 2). There was no difference between the groups in the degree of mouth opening (Table 3). However, the anaesthetist graded the conditions better for insertion in the two groups which received midazolam compared with those which did not (Table 3). Patients in groups 2 and 3 had a significant reduction in the incidence of pain with injection of propofol (Table 2).

Table 1
Table 1:
Patient demographic data
Table 2
Table 2:
Propofol requirements
Table 3
Table 3:
Conditions for laryngeal mask airway insertion

Discussion

The main findings of this study were that midazolam reduces the dose requirements for propofol (when given with fentanyl) to induce anaesthesia and permits insertion of a laryngeal mask. Midazolam also improved conditions for laryngeal mask insertion. Intravenous lidocaine had no effect on reducing propofol dose or improving conditions for laryngeal mask insertion.

Alfentanil–midazolampropofol combinations have been shown to be synergistic [12,13] for the induction of anaesthesia. Fentanyl and midazolam also act synergistically [14] and have been shown to reduce propofol requirements for induction of anaesthesia [15]. Fentanyl was used in this study, including the control, as it represents standard anaesthetic practice in our Institution. Lidocaine, as mentioned earlier, has also been shown to assist insertion of the laryngeal mask. We believe our study is the first to investigate conditions for laryngeal mask insertion using combinations of all three agents, i.e. fentanyl, lidocaine and midazolam.

The effect of midazolam on reducing propofol requirements for laryngeal mask insertion is similar to two studies by Driver and his colleagues that studied propofol and alfentanil with midazolam [5,6]. In these studies propofol was injected on a strict dose per kilogram basis, using three different dose regimens, whereas we infused propofol very slowly until the patient did not respond to verbal command. Slow injection of induction agents is known to reduce the total dose required to induce anaesthesia [16,17] and therefore might more accurately reflect the true induction dose. This was the reason behind the choice of the slow infusion rate, accepting this is not a common induction technique. A dose per kg induction with propofol, injected ‘quickly’, could potentially overestimate dose requirements. Comparing total propofol doses required to insert a laryngeal mask between this study and other midazolam co-induction studies show that they were very similar. However, considerably more patients in our study required additional boluses of propofol to achieve satisfactory conditions. Based on this finding, we believe that a bolus dose over 30 s of 1.25 mg kg−1 of propofol should be adequate to achieve adequate conditions for laryngeal mask insertion when preceded by fentanyl 1 µg kg−1 and midazolam 0.04 µg kg−1 and that slower infusions are unnecessary. This propofol dose is approximately half that recommended for healthy unpremedicated adults.

Intravenous lidocaine is known to suppress laryngeal reflexes [18,19,20] and has been used to improve conditions for laryngeal mask insertion after induction of anaesthesia with propofol [10] but has been less effective when given with thiopental [21]. In our study, lidocaine did not improve conditions for insertion or reduce propofol requirements.

An interesting finding was the reduction in the incidence of pain on injection of propofol in those patients receiving midazolam. This has been described before [22] but is not mentioned in a recent review of the subject [23]. In this study, midazolam was more effective than pre-injected lidocaine or fentanyl in reducing pain on injection but we cannot suggest a mechanism to explain this.

Midazolam co-induction significantly reduces propofol requirements for insertion of a laryngeal mask airway with obvious cost-saving implications. None of the patients who received midazolam required more than 200 mg for successful laryngeal mask insertion compared with six patients in each of the two groups who did not receive midazolam. This potential benefit of co-induction has recently been challenged by Anderson and his colleagues who found that pretreatment of patients with 30 mg of propofol 2 min prior to induction was equally effective as midazolam 2 mg in reducing propofol requirements [24]. However the end-point of their study was the patient tolerating a facemask. The work needs to be repeated to ascertain if the same results apply to laryngeal mask insertion.

A potential criticism of the use of midazolam is that it may prolong recovery time and delay discharge of patients to the ward. This could potentially offset any cost savings from the reduced amounts of propofol used. It would appear that this is not a valid concern. A study by Elwood has shown that the use of midazolam, in the doses used in our study, does not delay discharge after anaesthesia [25].

A further potential advantage of the reduced doses of propofol required for induction of anaesthesia and insertion of the laryngeal mask may be improved cardiovascular stability and reduced respiratory depression. It is known that the extent of the blood pressure reduction seen with propofol is dose dependant [26,27]. This present study did not aim to examine this aspect.

In conclusion, midazolam in combination with fentanyl reduces dose requirements for induction of anaesthesia with propofol and improves conditions for laryngeal mask insertion. There is no clinical benefit to be gained from the addition of lidocaine.

Acknowledgments

The authors are grateful to Messrs. Roche who provided financial support for this research.

References

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Keywords:

EQUIPMENT; laryngeal mask airway; ANAESTHESIA TECHNIQUES; co-induction; DRUGS; propofol; midazolam; lidocaine.

© 2001 European Academy of Anaesthesiology