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STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA
Brit. J. Anaesth. (1962), 34, 523
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA II: A METHOD FOR THE ASSESSMENT OF THEIR INFLUENCE ON THE COURSE OF ANAESTHESIA BY
JOHN W. DUNDEE, JAMES MOORE AND ROBERT M. NICHOLL
Department of Anaesthetics, The Queen's University of Belfast, Northern Ireland
The problems encountered in the evolution of a method for assessing the effect of pre-operative drugs on the course of anaesthesia are discussed. A method based on the use of methohexitone or thiopentone with nitrous oxide and oxygen for the operation of dilatation and curettage is described. The observations which it is feasible for the anaesthetist to record during the technique are described and methods for the analysis of data are discussed. The need has been stressed recently for a comprehensive study of the drugs given before anaesthesia. This must include an investigation of their effects before and after operation as well as their influence on the course of anaesthesia (Dundee, Moore and Nicholl, 1962). The authors have described a simple method for the evaluation of the effects of such drugs in the pre-operative period and this paper discusses the problems encountered in the study of their effects on the course of anaesthesia and describes a method which has proved satisfactory for this purpose. CHOICE OF SUBJECTS
able degree of hypotension. Operations of the type characterized by appreciable blood loss are not suitable and any postural changes (such as lithotomy or Trendelenburg position) must be the same in all procedures. Furthermore, large numbers of patients who conform to these criteria should be available, because many drugs require investigation and each series should contain a sufficient number of observations to permit valid statistical analysis of the data. These requirements are best met by patients scheduled for the operation of dilatation and curettage, who conform to the requirements of grades 1 and 2 physical status of the American Medical Association classification (A.M.A., 1954). Ideally they should all be under treatment in one hospital unit. An advantage of this choice is that it makes possible the use of a constant stimulus at the beginning of the operation, against which the response to the initial dose of barbiturate can be observed. The initial swabbing of the vulva and perineum with tincture of thiomersal is ideal for this purpose.
In order to minimize variables, the patients should be of the same sex and their ages should lie within narrow limits. (This is probably of more importance in the assessment of the pre-operative effects of drugs than in the present part of their evaluation.) Since certain pathological states influence the response of the patients to anaesthesia, subjects suffering from any severe systemic disease should be excluded from the study. ANAESTHESIA It is necessary to standardize the method of anaesthesia and, because techniques such as con- The technique must be sufficiently simple as to trolled respiration can of themselves cause hypo- be easily carried out by one anaesthetist while tension which may be indistinguishable from the allowing time for recording of relevant data. The effects of the premedication, the operative proce- number of agents given must be kept to a minidures must be simple, of fairly constant duration, mum and they must be capable of administration and not of themselves likely to cause any appreci- in easily measurable dosage or concentration. It is 523
Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on May 23, 2015
SUMMARY
524
* This is approximately equal to 0.5 ml of 5 per cent thiopentone or 2 per cent methohexitone per stone body weight, but a more precise nomogram for calculating the dose has been described by Dundee and Moore (1961a)
minutes after the end of the operation. Any possibility of diffusion hypoxia affecting such observations is minimized by the inhalation of a high flow of oxygen for 1 minute after discontinuation of the nitrous oxide. OBSERVATIONS DURING ANAESTHESIA
It is important that the anaesthetist knows in advance the particular observations which jt is necessary for him to record and this can be facilitated by the use of special record charts designed by Dundee and Moore (1961a). With the anaesthetic technique described the presence or absence of the following complications can be noted easily. Excitatory phenomena (skeletal muscle activity). Tremor or spontaneous involuntary muscle movement. (It is important not to confuse reflex movement due to stimulation and spontaneous movement caused by the anaesthetic agents.) Respiratory upset—cough and hiccough and laryngospasm. (Any complications resulting from untreated respiratory obstruction or premature insertion of an oropharyngeal airway must not be attributed to the anaesthetic.) Marked respiratory depression—indicating the necessity for assisting ventilation following the initial dose of barbiturate. It is difficult to record the severity of these complications without using an elaborate scheme which is unsuitable in clinical practice. However, allowance can be made for their severity in the grading scheme which will be described later. • Systolic blood pressure is recorded on the operating table immediately before the induction of anaesthesia, within 2 minutes of the initial injection of barbiturate and at intervals of 2-5 minutes thereafter. Thus, not only the incidence, but also the duration and the maximum severity of hypotension can be recorded. This also applies to the heart rate. A high flow of oxygen is given for one minute after the end of anaesthesia, and one minute later each patient is assessed as being: Awake: opens eyes either spontaneously or on command. Safe: protective reflexes present (pharyngeal active and good jaw tone). Unsafe: protective reflexes absent.
Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on May 23, 2015
recommended that the concentration of the inhalation agent should be kept constant and the dose of intravenous drugs varied with the requirements of individual patients. Since the use of muscle relaxants would prevent observations on respiratory disturbances during anaesthesia, they are best avoided in investigations of this nature. This also applies to the use of the potent inhalation agents cyclopropane, chloroform, halothane, and ether, which may cause hypotension with respiratory depression of a variable degree and duration. It is obvious from the foregoing that the barbiturate, nitrous oxide and oxygen sequence fulfils these requirements best. A constant flow of 6 l./min nitrous oxide and 2 l./min oxygen, given from a standard MagiU attachment with the expiratory valve opened as widely as possible, has proved satisfactory in practice. The involuntary or reflex movement of the patient must be the only indication for supplementary doses of the barbiturate, each of which should be just sufficient to abolish movement and produce tranquil operating conditions. So that antagonism or synergism between the premedication and the induction barbiturate may be studied it is recommended that a fixed induction dose (on a mg/kg basis) of barbiturate be given and total dose required for the operation be recorded. An induction dose of 4 mg/kg thiopentone or 1.6 mg/kg of methohexitone* is suitable for these cases and anaesthesia is maintained with the same drug as used for induction. (Reasons for preferring the latter agent will be discussed later.) The constant induction dose, given at a fixed rate of injection, also provides standard conditions for studying the effect of premedicants in modifying the hypotensive action of the barbiturate. Delay in recovery from anaesthesia may be due to a large dose of barbiturate having been given (either for a long operative procedure or because of the action of the premedication), or to the synergistic effect of the pre-operative drug and the barbiturate. If the first variable can be eliminated some information on the latter can be obtained by recording the condition of the patient 2
BRITISH JOURNAL OF ANAESTHESIA
525
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA—II
CHOICE OF BARBITURATE
Reference has already been made to the authors' choice of methohexitone in preference to thiopentone. This is based on a wide experience of both drugs, used as described here with a variety of premedicants, which has demonstrated that the incidence of excitatory phenomena with methohexitone is more affected by premedication than that which accompanies thiopentone. Furthermore, the "control" incidence with thiopentone (atropine premedication) is low and very large numbers would be required to demonstrate a significant reduction due to premedication. The following table shows the percentage incidences of excitatory phenomena found with both drugs with four forms of premedication and illustrates the reasons for preferring methohexitone in a study of this kind. Premedication Atropine Pethidine-atropine Promethazine-atropine Promethazine-hyoscine
Thiopentone
(2b) Slight upset during the induction period, which interfered with the course of anaesthesia but was not as marked as in grade 3. (3) Serious difficulties which, if untreated, make surgery impossible or place the patient's life in jeopardy (including severe prolonged hypotension). ANALYSIS OF DATA
The incidence of complications with different premedications can be compared using the y2 test and the mean of the total doses is compared by "t" test. The ridit analysis is valuable in comparing the distribution of grades in different series and its use for this purpose has been described by Dundee et al. (1961). Plans for a sequential analysis (with methohexitone, nitrous oxide and oxygen anaesthesia) which will make it possible to decide whether a form of premedication will result in a higher incidence of excitatory phenomena or a lower incidence of grade 1 anaesthesia than follows the use of atropine alone, have been described by Dundee and Moore, (1961b, c). While the basic criteria on which these have been based may vary from observer to observer, they can be useful when a large number of drugs are being studied. The characteristics for similar plans based on pethidine 100 mg with atropine 0.6 mg are as follows:
Methohexitone
7
28
4 17 69
6 81 100
h, K s
Incidence of excitatory phenomena + 2.383 -3.637 0.553 a-0.05
Incidence of grade 1 anaesthesia + 3.635 -2.383 0.477 /J-0.10
GRADING OF ANAESTHESIA
In order to permit an overall comparison of the course of anaesthesia with different forms of premedication, each administration is graded according to the scheme originally described by Dundee and Riding (1960) and modified by Dundee et al. (1961). (This is intended to "grade" the induction only, but in these short standard procedures it is applied to the whole anaesthetic.) The grades are as follows: (1) Smooth uncomplicated induction. (2a) Slight upset not interfering with the conduct of anaesthesia.
The maximum number of cases for both graphs is 35. Thus with this number of cases it is possible to decide, within the limits of error set out above, whether the addition of an anti-emetic or other drug to the pethidine-atropine premedication is likely to upset the course of the subsequent anaesthesia. OBSERVATIONS WITH THE METHOD
This method has already been used by Dundee and Moore (1961a) to study the effects of different intravenous barbiturates, and by Dundee and
Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on May 23, 2015
Experience has shown that, with a large number of cases on an operating list, it is not feasible for the single-handed anaesthetist to make any reliable assessment of the actual time of recovery. As in all these studies, the number of observers must be kept to a minimum and much practice with the anaesthetic method and technique of recording data is required before reliable, reproducible results can be obtained. This excludes the possibility of asking the assistance of the nursing staff in noting the actual time at which the patient wakens.
526
BRITISH JOURNAL OF ANAESTHESIA method may be too sensitive in detecting adverse effects of drugs and some of the findings may not be applicable with different forms of anaesthesia. However, it is unlikely that a dangerous form of premedication will not be detected even with a small number of cases using the above method. No apology is made for the detailed description of the method, and it must be emphasized that reliable results can only be obtained by meticulous attention to detail. REFERENCES
A.M.A. (1954). Fundamentals of Anesthesia, 3rd ed., p. 45. Philadelphia: Saunders. Dundee, J. W., and Moore, J. (1961a). Thiopentone and methohexital: a comparison as main anaesthetic agents for a standard operation. Anaesthesia, 16, 50. (1961b). The effect of scopolamine on methohexital anaesthesia. Anaesthesia, 16, 194. (1961c). The effects of premedication with phenothiazine derivatives on the course of methohexitone anaesthesia. Brit. J. Anaesth., 33, 382. Nicholl, R. M. (1962). Studies of drugs given before anaesthesia. I: A method of preoperative assessment. Brit. J. Anaesth., 34, 458. Riding, J. E. (1960). A comparison of Inactin and thiopentone as intravenous anaesthetics. Brit. J. Anaesth., 32, 206. Barron, p . W., and Nicholl, R. M. (1961). Some factors influencing the induction characteristics of methohexitone anaesthesia. Brit. J. Anaesth., 33, 296. Moore, J., and Dundee, J. W. (1961). Promethazine (its influence on the course of thiopentone and methohexital anaesthesia). Anaesthesia, 16, 61. SOMMA1RE
Les problemes rencontre's dans la mise au point d'une m6thode d'appre'ciation de l'effet des "pre'anesthe'siques" sont discuss par les auteurs, et une me'thode de'crite qui est base'e sur l'emploi de methohexitone ou de thiopentone avec de l'oxyde nitreux et de l'oxygfene, — pour emploi dans l'opdration de dilatation et de curettage. Les observations que Panesthdsiste a la possibility d'enr^gistrer pendant l'emploi de cette technique sont ddcrites. Les auteurs indiquent des m^thodes pour analyser les faits enre'gistre's et ils les discutent.
DISCUSSION
While the method described in this paper permits an assessment of the effects of premedication in patients having one form of anaesthesia, it is difficult to envisage an alternative technique which will yield so much data. It is intended only as a screening method and before it can be said with certainty that the drugs under study are safe for routine use, further trials with every commonly used form of anaesthesia are recommended. This
ZUSAMMENFASSUNG
Die Probleme werden besprochen, denen man bei der Entwicklung einer Methode zur Bestimmung der Wirkung praoperativer Medikamente auf den Narkose-Verlauf gegenubersteht. Eine Methode auf Grund der Anwendung von Methohexitone oder Thiopentone mit Lachgas und Sauerstoff fur den operativen Eingriff einer Dilatierung und Kurettage wird beschrieben. Die Beobachtungen, was der Anasthesiologe zweckmassigerweise wahrend der Technik misst, werden besprochen, und Methoden zur Analyse von Angaben erortert.
Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on May 23, 2015
Moore (1961b, c) and Moore and Dundee (1961) to investigate the influence of various forms of premedication on the course of action of one barbiturate. It is therefore not felt necessary to give examples of typical findings. The results obtained with four series each of 200 cases premedicated with either atropine 0.6 mg or pethidine 100 mg with atropine 0.6 mg and anaesthetized with either thiopentone or methohexitone have been analyzed. Each series consisted of equal numbers of patients having dilatation and curettage (D & C) and curettage without dilatation (C). The relevant findings are summarized below: (a) The average duration of anaesthesia was approximately the same in each series. (b) D & C operations on the average lasted longer than C, but the difference was only significant in one series. (c) In each series the course of anaesthesia and average total dose of barbiturate was similar for both operations. (d) The minimum number of cases (chosen at random from the total or chosen in consecutive order) which would give a reproducible frequency of complications and which was similar to the total of the series was 30. (e) In series varying in size from 30 to 50 cases, no observer difference was noted between the three authors, but this could be detected in other series collected by untrained observers. From the above it is recommended that: (1) Each series should be balanced to include equal numbers of D & C and C cases. (2) The minimum number of cases in any series should be 30, but 50 should be studied if possible. (3) Data from untrained observers should not be included.
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA II: A METHOD FOR THE ASSESSMENT OF THEIR INFLUENCE ON THE COURSE OF ANAESTHESIA BY
JOHN W. DUNDEE, JAMES MOORE AND ROBERT M. NICHOLL
Department of Anaesthetics, The Queen's University of Belfast, Northern Ireland
The problems encountered in the evolution of a method for assessing the effect of pre-operative drugs on the course of anaesthesia are discussed. A method based on the use of methohexitone or thiopentone with nitrous oxide and oxygen for the operation of dilatation and curettage is described. The observations which it is feasible for the anaesthetist to record during the technique are described and methods for the analysis of data are discussed. The need has been stressed recently for a comprehensive study of the drugs given before anaesthesia. This must include an investigation of their effects before and after operation as well as their influence on the course of anaesthesia (Dundee, Moore and Nicholl, 1962). The authors have described a simple method for the evaluation of the effects of such drugs in the pre-operative period and this paper discusses the problems encountered in the study of their effects on the course of anaesthesia and describes a method which has proved satisfactory for this purpose. CHOICE OF SUBJECTS
able degree of hypotension. Operations of the type characterized by appreciable blood loss are not suitable and any postural changes (such as lithotomy or Trendelenburg position) must be the same in all procedures. Furthermore, large numbers of patients who conform to these criteria should be available, because many drugs require investigation and each series should contain a sufficient number of observations to permit valid statistical analysis of the data. These requirements are best met by patients scheduled for the operation of dilatation and curettage, who conform to the requirements of grades 1 and 2 physical status of the American Medical Association classification (A.M.A., 1954). Ideally they should all be under treatment in one hospital unit. An advantage of this choice is that it makes possible the use of a constant stimulus at the beginning of the operation, against which the response to the initial dose of barbiturate can be observed. The initial swabbing of the vulva and perineum with tincture of thiomersal is ideal for this purpose.
In order to minimize variables, the patients should be of the same sex and their ages should lie within narrow limits. (This is probably of more importance in the assessment of the pre-operative effects of drugs than in the present part of their evaluation.) Since certain pathological states influence the response of the patients to anaesthesia, subjects suffering from any severe systemic disease should be excluded from the study. ANAESTHESIA It is necessary to standardize the method of anaesthesia and, because techniques such as con- The technique must be sufficiently simple as to trolled respiration can of themselves cause hypo- be easily carried out by one anaesthetist while tension which may be indistinguishable from the allowing time for recording of relevant data. The effects of the premedication, the operative proce- number of agents given must be kept to a minidures must be simple, of fairly constant duration, mum and they must be capable of administration and not of themselves likely to cause any appreci- in easily measurable dosage or concentration. It is 523
Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on May 23, 2015
SUMMARY
524
* This is approximately equal to 0.5 ml of 5 per cent thiopentone or 2 per cent methohexitone per stone body weight, but a more precise nomogram for calculating the dose has been described by Dundee and Moore (1961a)
minutes after the end of the operation. Any possibility of diffusion hypoxia affecting such observations is minimized by the inhalation of a high flow of oxygen for 1 minute after discontinuation of the nitrous oxide. OBSERVATIONS DURING ANAESTHESIA
It is important that the anaesthetist knows in advance the particular observations which jt is necessary for him to record and this can be facilitated by the use of special record charts designed by Dundee and Moore (1961a). With the anaesthetic technique described the presence or absence of the following complications can be noted easily. Excitatory phenomena (skeletal muscle activity). Tremor or spontaneous involuntary muscle movement. (It is important not to confuse reflex movement due to stimulation and spontaneous movement caused by the anaesthetic agents.) Respiratory upset—cough and hiccough and laryngospasm. (Any complications resulting from untreated respiratory obstruction or premature insertion of an oropharyngeal airway must not be attributed to the anaesthetic.) Marked respiratory depression—indicating the necessity for assisting ventilation following the initial dose of barbiturate. It is difficult to record the severity of these complications without using an elaborate scheme which is unsuitable in clinical practice. However, allowance can be made for their severity in the grading scheme which will be described later. • Systolic blood pressure is recorded on the operating table immediately before the induction of anaesthesia, within 2 minutes of the initial injection of barbiturate and at intervals of 2-5 minutes thereafter. Thus, not only the incidence, but also the duration and the maximum severity of hypotension can be recorded. This also applies to the heart rate. A high flow of oxygen is given for one minute after the end of anaesthesia, and one minute later each patient is assessed as being: Awake: opens eyes either spontaneously or on command. Safe: protective reflexes present (pharyngeal active and good jaw tone). Unsafe: protective reflexes absent.
Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on May 23, 2015
recommended that the concentration of the inhalation agent should be kept constant and the dose of intravenous drugs varied with the requirements of individual patients. Since the use of muscle relaxants would prevent observations on respiratory disturbances during anaesthesia, they are best avoided in investigations of this nature. This also applies to the use of the potent inhalation agents cyclopropane, chloroform, halothane, and ether, which may cause hypotension with respiratory depression of a variable degree and duration. It is obvious from the foregoing that the barbiturate, nitrous oxide and oxygen sequence fulfils these requirements best. A constant flow of 6 l./min nitrous oxide and 2 l./min oxygen, given from a standard MagiU attachment with the expiratory valve opened as widely as possible, has proved satisfactory in practice. The involuntary or reflex movement of the patient must be the only indication for supplementary doses of the barbiturate, each of which should be just sufficient to abolish movement and produce tranquil operating conditions. So that antagonism or synergism between the premedication and the induction barbiturate may be studied it is recommended that a fixed induction dose (on a mg/kg basis) of barbiturate be given and total dose required for the operation be recorded. An induction dose of 4 mg/kg thiopentone or 1.6 mg/kg of methohexitone* is suitable for these cases and anaesthesia is maintained with the same drug as used for induction. (Reasons for preferring the latter agent will be discussed later.) The constant induction dose, given at a fixed rate of injection, also provides standard conditions for studying the effect of premedicants in modifying the hypotensive action of the barbiturate. Delay in recovery from anaesthesia may be due to a large dose of barbiturate having been given (either for a long operative procedure or because of the action of the premedication), or to the synergistic effect of the pre-operative drug and the barbiturate. If the first variable can be eliminated some information on the latter can be obtained by recording the condition of the patient 2
BRITISH JOURNAL OF ANAESTHESIA
525
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA—II
CHOICE OF BARBITURATE
Reference has already been made to the authors' choice of methohexitone in preference to thiopentone. This is based on a wide experience of both drugs, used as described here with a variety of premedicants, which has demonstrated that the incidence of excitatory phenomena with methohexitone is more affected by premedication than that which accompanies thiopentone. Furthermore, the "control" incidence with thiopentone (atropine premedication) is low and very large numbers would be required to demonstrate a significant reduction due to premedication. The following table shows the percentage incidences of excitatory phenomena found with both drugs with four forms of premedication and illustrates the reasons for preferring methohexitone in a study of this kind. Premedication Atropine Pethidine-atropine Promethazine-atropine Promethazine-hyoscine
Thiopentone
(2b) Slight upset during the induction period, which interfered with the course of anaesthesia but was not as marked as in grade 3. (3) Serious difficulties which, if untreated, make surgery impossible or place the patient's life in jeopardy (including severe prolonged hypotension). ANALYSIS OF DATA
The incidence of complications with different premedications can be compared using the y2 test and the mean of the total doses is compared by "t" test. The ridit analysis is valuable in comparing the distribution of grades in different series and its use for this purpose has been described by Dundee et al. (1961). Plans for a sequential analysis (with methohexitone, nitrous oxide and oxygen anaesthesia) which will make it possible to decide whether a form of premedication will result in a higher incidence of excitatory phenomena or a lower incidence of grade 1 anaesthesia than follows the use of atropine alone, have been described by Dundee and Moore, (1961b, c). While the basic criteria on which these have been based may vary from observer to observer, they can be useful when a large number of drugs are being studied. The characteristics for similar plans based on pethidine 100 mg with atropine 0.6 mg are as follows:
Methohexitone
7
28
4 17 69
6 81 100
h, K s
Incidence of excitatory phenomena + 2.383 -3.637 0.553 a-0.05
Incidence of grade 1 anaesthesia + 3.635 -2.383 0.477 /J-0.10
GRADING OF ANAESTHESIA
In order to permit an overall comparison of the course of anaesthesia with different forms of premedication, each administration is graded according to the scheme originally described by Dundee and Riding (1960) and modified by Dundee et al. (1961). (This is intended to "grade" the induction only, but in these short standard procedures it is applied to the whole anaesthetic.) The grades are as follows: (1) Smooth uncomplicated induction. (2a) Slight upset not interfering with the conduct of anaesthesia.
The maximum number of cases for both graphs is 35. Thus with this number of cases it is possible to decide, within the limits of error set out above, whether the addition of an anti-emetic or other drug to the pethidine-atropine premedication is likely to upset the course of the subsequent anaesthesia. OBSERVATIONS WITH THE METHOD
This method has already been used by Dundee and Moore (1961a) to study the effects of different intravenous barbiturates, and by Dundee and
Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on May 23, 2015
Experience has shown that, with a large number of cases on an operating list, it is not feasible for the single-handed anaesthetist to make any reliable assessment of the actual time of recovery. As in all these studies, the number of observers must be kept to a minimum and much practice with the anaesthetic method and technique of recording data is required before reliable, reproducible results can be obtained. This excludes the possibility of asking the assistance of the nursing staff in noting the actual time at which the patient wakens.
526
BRITISH JOURNAL OF ANAESTHESIA method may be too sensitive in detecting adverse effects of drugs and some of the findings may not be applicable with different forms of anaesthesia. However, it is unlikely that a dangerous form of premedication will not be detected even with a small number of cases using the above method. No apology is made for the detailed description of the method, and it must be emphasized that reliable results can only be obtained by meticulous attention to detail. REFERENCES
A.M.A. (1954). Fundamentals of Anesthesia, 3rd ed., p. 45. Philadelphia: Saunders. Dundee, J. W., and Moore, J. (1961a). Thiopentone and methohexital: a comparison as main anaesthetic agents for a standard operation. Anaesthesia, 16, 50. (1961b). The effect of scopolamine on methohexital anaesthesia. Anaesthesia, 16, 194. (1961c). The effects of premedication with phenothiazine derivatives on the course of methohexitone anaesthesia. Brit. J. Anaesth., 33, 382. Nicholl, R. M. (1962). Studies of drugs given before anaesthesia. I: A method of preoperative assessment. Brit. J. Anaesth., 34, 458. Riding, J. E. (1960). A comparison of Inactin and thiopentone as intravenous anaesthetics. Brit. J. Anaesth., 32, 206. Barron, p . W., and Nicholl, R. M. (1961). Some factors influencing the induction characteristics of methohexitone anaesthesia. Brit. J. Anaesth., 33, 296. Moore, J., and Dundee, J. W. (1961). Promethazine (its influence on the course of thiopentone and methohexital anaesthesia). Anaesthesia, 16, 61. SOMMA1RE
Les problemes rencontre's dans la mise au point d'une m6thode d'appre'ciation de l'effet des "pre'anesthe'siques" sont discuss par les auteurs, et une me'thode de'crite qui est base'e sur l'emploi de methohexitone ou de thiopentone avec de l'oxyde nitreux et de l'oxygfene, — pour emploi dans l'opdration de dilatation et de curettage. Les observations que Panesthdsiste a la possibility d'enr^gistrer pendant l'emploi de cette technique sont ddcrites. Les auteurs indiquent des m^thodes pour analyser les faits enre'gistre's et ils les discutent.
DISCUSSION
While the method described in this paper permits an assessment of the effects of premedication in patients having one form of anaesthesia, it is difficult to envisage an alternative technique which will yield so much data. It is intended only as a screening method and before it can be said with certainty that the drugs under study are safe for routine use, further trials with every commonly used form of anaesthesia are recommended. This
ZUSAMMENFASSUNG
Die Probleme werden besprochen, denen man bei der Entwicklung einer Methode zur Bestimmung der Wirkung praoperativer Medikamente auf den Narkose-Verlauf gegenubersteht. Eine Methode auf Grund der Anwendung von Methohexitone oder Thiopentone mit Lachgas und Sauerstoff fur den operativen Eingriff einer Dilatierung und Kurettage wird beschrieben. Die Beobachtungen, was der Anasthesiologe zweckmassigerweise wahrend der Technik misst, werden besprochen, und Methoden zur Analyse von Angaben erortert.
Downloaded from http://bja.oxfordjournals.org/ at Pennsylvania State University on May 23, 2015
Moore (1961b, c) and Moore and Dundee (1961) to investigate the influence of various forms of premedication on the course of action of one barbiturate. It is therefore not felt necessary to give examples of typical findings. The results obtained with four series each of 200 cases premedicated with either atropine 0.6 mg or pethidine 100 mg with atropine 0.6 mg and anaesthetized with either thiopentone or methohexitone have been analyzed. Each series consisted of equal numbers of patients having dilatation and curettage (D & C) and curettage without dilatation (C). The relevant findings are summarized below: (a) The average duration of anaesthesia was approximately the same in each series. (b) D & C operations on the average lasted longer than C, but the difference was only significant in one series. (c) In each series the course of anaesthesia and average total dose of barbiturate was similar for both operations. (d) The minimum number of cases (chosen at random from the total or chosen in consecutive order) which would give a reproducible frequency of complications and which was similar to the total of the series was 30. (e) In series varying in size from 30 to 50 cases, no observer difference was noted between the three authors, but this could be detected in other series collected by untrained observers. From the above it is recommended that: (1) Each series should be balanced to include equal numbers of D & C and C cases. (2) The minimum number of cases in any series should be 30, but 50 should be studied if possible. (3) Data from untrained observers should not be included.