Department of Anaesthetics, Royal Infirmary, Edinburgh EH3 9YW, UK*Corresponding author
Presented to the Anaesthetic Research Society, Aberdeen, 25th March 1999 (Br J Anaesth 1999; 83: P1801).
Accepted for publication: January 9, 2001
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Abstract |
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Br J Anaesth 2001; 86: 63944
Keywords: ventilation, pattern; anaesthetics i.v.; anaesthesia, induction
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Introduction |
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Propofol and barbiturates are two commonly used anaesthetic induction agents; and for day case surgery, inhalation induction with sevoflurane is becoming more common.7 However, some induction methods require considerable co-operation from the patient, such as vital capacity breaths or breath holding.8 Asking the patient to hold their breath helps to prevent apnoea after induction of anaesthesia, but can upset the continued uptake of the anaesthetic. Respiration can also be better maintained if re-breathing is allowed to offset the effects of hypocapnia.9 10 In our studies of this topic, we noted that breathing frequency and pattern changed noticeably and promptly to a different, regular pattern which could give an early and reliable index of loss of consciousness.
We designed the present study to compare the onset of regular breathing pattern with other frequently used end points of anaesthetic induction, both clinical and those used in investigations. We used three different induction agentspropofol, methohexitonal, and sevoflurane which have possibly different patterns of action. We compared change in pattern of breathing with the more conventional estimates of induction of anaesthesia. We also considered the contention that conventional estimates of anaesthetic induction are not equivalent.
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Methods |
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We used a blocked, randomized, parallel design. Patients were allocated in blocks of 30 to receive either propofol, methohexitonal, or sevoflurane as an induction agent by sealed envelopes. Three were withdrawn for technical reasons after allocation. These choices were replaced.
As the rate of administration of i.v. agents would affect the time taken to administer an induction dose, and the rate of administration affects the induction dose required, we attempted to give each patient the appropriate dose in the same time. We estimated the induction dose of thiopental, using the regression equation of Avram,11 which takes age and weight into account:
Dose of thiopental (mg)=295+weight (kg)age (yr)x1.86
The estimated induction dose (EID) of the i.v. agents was calculated using a relative potency for methohexital of 4.9312 and 0.53 for propofol (personal data). This dose was increased by 50%, made up to 30 ml using 0.9% saline, and given from a Graseby 3500 syringe driver set to run at 800 ml h1, so that the EID would be given in about 90 s. The injection continued until all the end points had been reached or 150% of the EID had been given. The method of induction with sevoflurane did not require any change in the patients breathing. We added sevoflurane 0.5% to the fresh gas. After three breaths, this was doubled to 1%. The concentration was doubled after each three breaths until the maximum concentration of 8% was reached. This level was then maintained until all the end points had been reached.
The patients were monitored with ECG, non-invasive arterial pressure, and pulse oximetry. Arterial pressure readings were not taken during induction of anaesthesia. Before induction started, the patient breathed from a coaxial Mapleson D circuit supplied with oxygen 3 litre min1 and fitted with a pneumotachograph and a sidestream carbon dioxide analyser (Datex Cardiocap II). A good mask seal was obtained, checked by movement of the reservoir bag and a carbon dioxide trace that showed a satisfactory expiratory plateau and a secondary peak during inspiration, indicating re-breathing. The pressure from the pneumotachograph was measured with a transducer (Furness) and recorded with a digital logging device (Dash IV). A second channel recorded a signal voltage used to mark the end points of induction. The device also gave a paper printout of the two signals at 20 mm s1. After 45 s of regular breathing had been recorded, induction of anaesthesia was commenced.
Each patient lay supine on a horizontal table and a vein on the dorsum of the left hand was cannulated and connected to the infusion pump if appropriate. Before breathing from the mask was started, the right arm was held raised and straight, at 45% to the horizontal and away from the side of the body. The patient gripped a steel cylinder, 10 cm long, and 1.5 cm diameter, between the first finger and thumb of her right hand. She was asked to tap regularly with the index finger of the left hand, and to keep tapping, keep hold of the weight, and keep the arm up for as long as possible. The patients lash reflex was tested every 15 s. The signal voltage to the recorder was switched to indicate the time the lash reflex vanished, when the patient finally stopped tapping her index finger, when her right arm came down to become horizontal, (loss of muscle tone) and when the weight was dropped. When all the end points were reached and a change in breathing pattern had been noted, or after the entire i.v. dose had been given, the recording was stopped and anaesthesia continued as indicated clinically. If the entire dose of methohexital or propofol was given without all the end points having occurred, only those end points that had been reached were analysed.
A separate printout was made of the respiratory flow record and coded to conceal the agent and patient from a single observer who measured the time that the pattern of respiration changed (Fig. 1). If there was no clear changeover in breathing pattern, the end of the last recognizable conscious breath and the start of the first recognizable unconscious breath were chosen and the midpoint calculated. We measured the time from start of induction to the time to achieve the other end points from the recording of the events.
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Results |
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One patient who received methohexital failed to drop the weight and this patient and five others (two propofol, three methohexital) still had a lash reflex after the entire i.v. dose had been given.
Propofol had a more rapid effect than the other agents. Apart from the lash reflex, the pattern of change in the end points was remarkably consistent (Figs. 2 and 3). Comparison of the agents using ANOVA showed that there were highly significant differences between the agents, using all the measures of induction. However, only with tapping, tone, and grip did the 95% CI for each distribution not overlap.
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For methohexital, but not for the other agents, there was a significant difference (P<0.01) in the coefficients of variance of each index. With this agent, the greatest coefficient of variation is for the lash reflex (Table 2).
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Discussion |
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For several reasons, we chose to compare times rather than doses in this study. First, the pattern of response loss was of more importance than the actual doses used. Second, one of the agents was inhaled, and estimating the dose was not possible, particularly since as soon as the breathing pattern changed, the plateau pattern of exhaled gas composition was lost. However, it is likely that with induction occurring over this short period of time, the alveolar concentration of sevoflurane would still be increasing progressively.8 29 Third, the kinetics of induction are far from simple30 even though we chose drug infusion rates (typically about 160 mg kg1 h1) that would have reduced the influence of administration rate on time to induction, and to a lesser extent the effect of administration rate on dose requirement.26 The inter-relationship between kinetics and drug effect make acute studies, such as this one, uncertain grounds for speculation about drug effects. For example, propofol had a more rapid onset than we expected (i.e. appeared more potent), perhaps because the solution was diluted.26
Comparison of end points for a single drug are more valid, because the drug effect in this study will certainly have been progressively increasing. Previous studies have shown differences in slope of doseresponse relationships for different end points, with the lash reflex generally having a greater variation in dose requirement.5 20 We were surprised to find that breathing was such a sensitive indicator of anaesthetic effect. This suggests that the change in respiration is a sign of withdrawal of conscious control, which occurs before loss of other cortical control such as finger tapping. Another volitional act, handgrip, was extremely resistant to depression. Our impression was that this function appeared in our patients to have become a component of muscle tone. Our results are at variance with those of a study where propofol was slowly infused in volunteers, when a weight was dropped while the subject was awake, and before the lash reflex was lost.20 Apart from the lash reflex, breathing change showed greater variation than the other tests, but this difference was not significant. A practical conclusion of this study is that breathing change is a sensitive index, but not very exact; and the most reliable and simple index is dropping of the outstretched arm, which is generally easily used clinically.
The response that is clearly different from the others is the lash reflex. Part of the greater variability of this measure might be caused by the intermittent measurements, but this could not explain the differences between agents. Anaesthesia is now not considered to be a single phenomenon.3133 In contrast to our other tests, which could be measures of a cortically mediated obtunding effect, the lash reflex may indicate an immobilizing effect that is less dependent on cortical effects,34 although other studies have found a close relationship between lash reflex and response to verbal command2 during propofol infusions. Further comparison between different agents with clinically relevant endpoints is justified.35
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Acknowledgement |
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References |
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