Influence of nitrous oxide on induction of anaesthesia with sevoflurane

H. O’Shea, S. Moultrie and G. B. Drummond

Department of Anaesthetics, Critical Care, and Pain Medicine, Royal Infirmary, Edinburgh EH3 9YW, UK*Corresponding author

{dagger}Published in abstract form: Br J Anaesth 2000; 85: 156P.

Accepted for publication: March 29, 2001


    Abstract
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 Abstract
 Introduction
 Methods and results
 Comments
 References
 
Nitrous oxide is often used during inhalation induction of anaesthesia with sevoflurane. Although the value of using nitrous oxide during inhalation induction with other volatile anaesthetics has been studied, the popularity of sevoflurane induction and the different characteristics of this agent make a study of the combination of nitrous oxide with this agent of interest. We compared induction times, oxygenation, and excitatory events during inhalation induction of anaesthesia using sevoflurane, with and without nitrous oxide. We studied 64 female patients, randomly allocated to receive inhalation induction of anaesthesia using sevoflurane with or without 50% nitrous oxide in the fresh gas, using a co-axial breathing system (Mapleson D) and a fresh gas flow rate of 3–6 litre min–1. Mean time to induction of anaesthesia (fall of an outstretched arm) was 102 s in both groups, but excitation (limb or head movement) was more frequent in those receiving nitrous oxide (10 patients) than in those receiving oxygen only (five patients) (P<0.05). Oxygenation was similar in both groups. We conclude that nitrous oxide confers no advantage when anaesthesia is induced with sevoflurane in this way.

Br J Anaesth 2001; 87: 286–8

Keywords: anaesthetics volatile, sevoflurane; anaesthetic gases, nitrous oxide; anaesthetic techniques, inhalation; anaesthetic techniques, induction


    Introduction
 Top
 Abstract
 Introduction
 Methods and results
 Comments
 References
 
Sevoflurane is a popular agent for inhalation induction of anaesthesia, primarily because of its acceptability by lack of irritation.1 The speed of onset of anaesthesia is rapid, and although nitrous oxide is often added to the inhaled gases, there is only little evidence that the combination is much better than sevoflurane used alone.2 3 We carried out a study to investigate the effects of nitrous oxide on speed and quality of inhalation induction, using a method that requires minimal cooperation from the patient.4


    Methods and results
 Top
 Abstract
 Introduction
 Methods and results
 Comments
 References
 
After ethics committee approval, we recruited 64 ASA I and II patients about to have gynaecological surgery. Each patient gave written informed consent. No premedication was given. When the patient arrived in the anaesthetic room, an i.v. cannula was placed in the hand and monitors attached (ECG, finger pulse oximetry, non-invasive arterial pressure). After baseline readings were taken, no further arterial pressure measurements were taken during the induction to avoid discomfort. The patient lay supine and horizontal, and was asked to keep one arm held straight out, about 30% up from the horizontal, for as long as possible during the induction. Induction time was taken as the time from the first addition of sevoflurane to the carrier gas, to the time the arm fell to the horizontal. Immediately before induction of anaesthesia, patients were allocated by flipping a coin to receive either nitrous oxide or oxygen alone as the carrier gas, and were not told of this allocation.

A disposable Mapleson D co-axial breathing circuit (Bain circuit) was used. Gas for carbon dioxide analysis (Datex Cardiocap 3) was sampled from the gas source side of a filter fitted to the mask. The flow rate was first set at 10 litre min–1 of oxygen. A well fitting facemask was applied and the patient was instructed to breathe normally. The reservoir bag and the capnograph were carefully observed to ensure that no leaks were present, and that a secondary peak of carbon dioxide concentration was present during inspiration, indicating partial rebreathing. After the patient had taken three satisfactory breaths, the gas flow was reduced, to either oxygen of 3 or 1.5 litre min–1 and nitrous oxide 1.5 litre min–1 according to the random allocation. At the same time 0.5% sevoflurane was set on the vapourizer. After each subsequent three breaths, the sevoflurane concentration was doubled until 8% was reached. If coughing occurred, the concentration increase was not applied until breathing was settled for three breaths. After the sevoflurane concentration had been maintained at 8% for 15 s, fresh gas flow was increased to 6 litre min–1. Any excitatory events such as vocalization, or movements of the head, neck, body or limbs, or reduction of the pulse oximeter reading to less than 94%, was noted. We also noted any cessation of breathing movements for more than 10 s, which was considered to be apnoea.

The study stopped when the arm had come down, and anaesthesia was continued as appropriate clinically. Values are expressed as mean (SD) and compared between the groups with Student’s t-test (induction time) and the chi-squared test (excitation and apnoea) (Minitab v. 13.1). We accepted P<0.05 as significant.

Twenty-six patients received nitrous oxide and oxygen, and 36 patients received oxygen only, as carrier gas. The features and the induction characteristics of the groups are shown in Table 1. The two groups were similar in age and weight. Induction times were very similar: 102 (24) s with nitrous oxide/oxygen, and 102 (27) s with oxygen. The 95% confidence limits for a difference in these times are ±13 s.


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Table 1 Features of patients and characteristics of induction in groups receiving and not receiving nitrous oxide
 
Excitation was more frequent (10 out of 26) in the group receiving nitrous oxide than in those who received oxygen (five out of 36) (P<0.05). Reduction in SpO2. values to less than 94% occurred in two patients breathing oxygen and one patient receiving nitrous oxide, and no decreases were seen in association with excitatory side effects. Apnoea for 16 s occurred in one patient who received sevoflurane in oxygen, without excitation or a decrease in SpO2.


    Comments
 Top
 Abstract
 Introduction
 Methods and results
 Comments
 References
 
Sevoflurane and nitrous oxide are commonly used together for induction of anaesthesia5 6 despite few studies to support the use of this combination. Hall and co-workers compared inhalation induction, using a single breath method, using 8% sevoflurane in either oxygen or 67% nitrous oxide. They found no significant difference in time to induction or complications: moderate excitation in six out of 15 subjects receiving oxygen and three out of 16 receiving nitrous oxide.3 In that study, they used a vital capacity method which requires some co-operation from the patient, whereas we used a method that relies on mild rebreathing to maintain ventilation during the period of loss of consciousness, and only requires the patient to breathe normally.4

The time to induction of anaesthesia in our study was greater than in other studies of inhalation induction, which report times of about 1 min3 6 presumably because we increased the fresh gas vapour concentration gradually, over about 30 s. However the increased time was offset by the small incidence of excitation and apnoea, which was less than reported by others.3 5 6

We did not conceal the use of the carrier gas from the anaesthetist giving the anaesthetic. Although studies that involve an observer assessment of quality should be double blind, we limited our assessment to features that we considered unambiguous: pulse oximeter readings, breathing movements, arm position, and any movement of the head or limbs. Different measures are used to define the induction of anaesthesia, but we have found that the measure we used in this study is equivalent to others, such as loss of voluntary finger tapping.7 Arm position gave an easily visible endpoint without needing intermittent stimulation of the patient as would occur with finger tapping or loss of lash reflex. It can be affected by excitatory side effects, and in two patients, excitatory effects made the endpoint of arm lowering equivocal. Exclusion of these times from analysis did not affect the statistical conclusion. We studied a sufficient number of patients to find a significant difference in minor and generally clinically insignificant excitation during induction, and found that nitrous oxide had no effect on the time for induction of anaesthesia.

In theory, nitrous oxide can speed induction of anaesthesia by adding its effect to that of sevoflurane, and also perhaps by the second gas effect. However, the concentrations used in this study would limit the importance of the latter mechanism. We cannot be certain what the inspired concentration of nitrous oxide would have been. It would have been less than 50% because of the limited fresh gas flow, and would have increased progressively during the induction process, perhaps reaching excitatory concentrations towards the time at which sevoflurane would be affecting consciousness as well. The system would also have contained some residual nitrogen from the patient’s lungs. By using nitrous oxide in the carrier gas, the benefits of pre-oxygenation will be reduced or abolished, with no clear benefit on the process of induction.

We conclude that in young unpremedicated patients, nitrous oxide confers no advantage when added to sevoflurane for inhalation induction.


    References
 Top
 Abstract
 Introduction
 Methods and results
 Comments
 References
 
1 Doi M, Ikeda K. Airway irritation produced by volatile anaesthetics during brief inhalation: comparison of halothane, enflurane, isoflurane and sevoflurane. Can J Anaesth 1993; 40: 126–6

2 Yurino M, Kimura H. A comparison of vital capacity breath and tidal breathing techniques for induction of anaesthesia with high sevoflurane concentrations in nitrous oxide and oxygen. Anaesthesia 1995; 50: 308–11[ISI][Medline]

3 Hall JE, Stewart JIM, Harmer M. Single-breath inhalation induction of sevoflurane anaesthesia with and without nitrous oxide: a feasibility study in adults and comparison with an intravenous bolus of propofol. Anaesthesia 1997; 52: 410–5[ISI][Medline]

4 Guracha Boru K, Drummond GB. Comparison of breathing methods for inhalation induction of anaesthesia. Br J Anaesth 1999; 83: 650–3[Abstract/Free Full Text]

5 Thwaites A, Edmends S, Smith I. Inhalational induction with sevoflurane: a double-blind comparison with propofol. Br J Anaesth 1997; 78: 356–65[Abstract/Free Full Text]

6 Philip BK, Lombard LL, Roaf ER, Drake AF, Calalang I, Philip JH. Comparison of vital capacity induction with sevoflurane to intravenous induction with propofol for adult ambulatory anesthesia. Anesth Analg 1999; 89: 623–7[Abstract/Free Full Text]

7 Strickland TL, Drummond GB Comparison of signs of anaesthesia using propofol, methohexital and sevoflurane. Br J Anaesth 1999; 83: 180P–1P