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STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA
Brit. J. Anaesth. (1962), 34, 527
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA HI: A METHOD FOR THE STUDYING OF THEIR EFFECTS ON POSTOPERATIVE VOMITING AND NAUSEA BY
JOHN W. DUNDEE, ROBERT M. NICHOLL AND JAMES MOORE
Department of Anaesthetics, The Queen's University of Belfast, Northern Ireland SUMMARY
In the two previous papers in this series, the need mentioned (Smessaert, Schehr and Artusio, 1959; for a comprehensive study of the drugs given Belville, Bross and Howland, 1959a, b, 1960; before anaesthesia was stressed and methods were Belville, Howland and Bross, 1960). described for investigating their effects in the preCHOICE OF PATIENTS AND OPERATION operative period and their influence on the course of anaesthesia (Dundee, Moore and Nicholl, In addition to the pre-anaesthetic medication 1962a, b). This publication describes a method there is suggestive, if not always conclusive, for studying the incidence and severity of post- evidence that other factors influence the degree operative emetic symptoms which follow their and severity of postoperative emetic symptoms. use. These include the sex of the patient (Knapp and It is improbable that drugs which cause a high Beecher, 1956; Burtles and Peckett, 1957; Scurr incidence of other sequelae, such as hypotension, and Robbie, 1958), the nature and duration of are likely to come into clinical use. However, the operative procedure (Davies, 1941; Dent, there is convincing evidence to incriminate the Ramachandra and Stephen, 1955; Bodman, pre-operative use of the potent analgesics as a Morton and Thomas, 1960) and the anaesthetic major factor in causing postoperative vomiting technique employed (Cook, 1931; Gillespie, and nausea under certain circumstances ( J a 1 u e - 1950; Wolfe, 1952). Because these factors are noud and Mercier, 1951; Phillips et al., 1958; of unknown importance it is essential to control Riding, 1960). This undesirable side effect of as many variables as possible within the limits their action has been very inadequately studied, of clinical practice. This can be achieved by but is receiving more attention since the intro- limiting observations to females operated on for duction of the anti-emetic drugs. The lack of dilatation and curettage under a standard anaesappreciation of the importance of premedication thetic technique of a barbiturate, nitrous oxide as a factor influencing postoperative vomiting is and oxygen as described by Dundee and Moore shown by the many publications on the emetic (1961a, b, c) and Moore and Dundee (1961). sequelae of anaesthesia in which this factor is The significance of the variations in the duraeither ignored (Cook, 1931; Kaye, 1936; Adriani, tion of anaesthesia in a large series of cases will Summers and Antony, 1961), or else the nature be discussed later, as will the significance of the of the drug given before anaesthesia is not even difference in procedure between patients under527
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A complete study of the effects of drugs given before operation necessitates an investigation of the incidence and severity of postoperative emetic symptoms which might be attributable to their use. A method of such a study is described. The limitation of observations to patients anaesthetized with a standard anaesthetic technique for minor gynaecological operations reduces, as far as is clinically possible, the variable factors which could invalidate the findings. A scoring system for grading the severity of emetic signs and symptoms is described, and the importance of the choice of anaesthetic and the nature and duration of the operation is discussed.
528
These variables must be eliminated to obtain reliable data and the findings to be reported by the authors were all obtained in one hospital unit in which it was possible to ensure uniformity in regard to these factors. OBSERVATIONS
These are all made during the first 6 hours after the end of the operation, for although Wangeman and Hawk (1942) and Comroe and Dripps (1948) found that the effects of the potent analgesics may last beyond this time, it is unlikely that vomiting resulting from their administration will start for the first time about 7 hours or more after their injection. Furthermore, patients' habits as regards meals and ambulation may play a part in the incidence of vomiting and nausea, if this time is exceeded. This method will therefore give a time incidence of postoperative emetic symptoms which can be attributed to premedication, but the 6-hour time limit on observations must be remembered when considering their severity. Observations are limited to those which can be easily carried out by a single anaesthetist on a large number of patients, and this excluded a study of the total number of emetic episodes or the volume of the vomitus, as carried out by Boulton (1955) and Moore et al. (1955, 1956, 1958). Boulton has stressed the importance of recording the number of times the patient vomited when assessing the efficacy of anti-emetic drugs. He points out that "emergence" vomit of secretions collected in the stomach and oesophagus during operation is a frequent occurrence, which will not be affected by an anti-emetic drug, but such a drug will be expected to reduce the incidence of further episodes of vomiting. While this may apply to prolonged operations it is not likely to be an important factor in the present studies. All patients are seen by one of the authors at the end of the first hour after operation and as near as possible to 5 hours later. Emetic symptoms are classed as "vomiting" (which includes retching) or "nausea", but when both occurred this is recorded as "vomiting". Vomiting or retching occurring at the end of anaesthesia is noted, irrespective of whether consciousness has returned or not. The
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going cervical dilatation and uterine curettage (D & C) and those having curettage without preliminary dilatation of the cervix (C) (as in incomplete abortion). The brevity of this operation ensures that the effects of the drugs used in premedication persist into the postoperative period, and the incidence and severity of emetic symptoms can be related to the drugs given before anaesthesia. Patients also recover rapidly from the short anaesthesia and episodes of vomiting in an unconscious patient are unlikely to escape notice. Emergence vomiting is frequently ignored in studies of this nature, leading to an erroneously low incidence of emetic symptoms. Analgesics are not required after operation and so the effect of postoperative drugs does not vitiate the findings. Furthermore, large numbers of subjects are readily available and the factors of unknown importance which are outside the control of the anaesthetist, such as a history of motion sickness (Smith, 1934; Armer, 1952; Burtles and Peckett, 1957), can be minimized. Limitation of the choice of subjects to those in good physical condition (Dundee, Moore and Nicholl, 1962a) excludes patients with ketosis which has been incriminated as an aetiological factor in postoperative vomiting by Harris (1951) and Jaquenoud and Mercier (1951). It also ensures that they fall within certain age limits, which Burtles and Peckett have shown may well be another important consideration. Much has been written about the importance of the skill of the anaesthetist as a factor to be considered when studying postoperative emetic symptoms, but there are no specific data to suggest that this is an important factor. In the present studies, all anaesthetics have been given by the authors or by junior colleagues working under their direct supervision. The importance in having all patients in one hospital unit has not been adequately stressed in the published literature on this topic. The routine as regards time of operation, postoperative ambulation, visiting hours and meal times varies from hospital to hospital and ward to ward, and patients who are left alone for several hours after operation are less likely to be sick than those who are disturbed by visitors or given a meal or drinks early in the postoperative period.
BRITISH JOURNAL OF ANAESTHESIA
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA—III
ANALYSIS OF FINDINGS
The incidence of symptoms in the three time periods outlined above can be analyzed using the standard x2 test. There are obvious limitations to the value of this procedure, because the overall severity of the symptoms is not demonstrated. In addition to this a scoring scheme has been devised, based on that used by Belville, Brass and Howland (1959a). This combines the findings obtained during the first hour after the end of operation with those in the later period and thus gives a better overall picture of the severity of the emetic symptoms. The scoring scheme is shown in table I and is based on certain assumptions which seem valid to the authors. (a) Vomiting is more distressing and dangerous than nausea. (b) Early (0-1 hour) vomiting is more dangerous than late (1-6 hours) vomiting. TABLE I
Scheme for assessing severity of postoperative emetic symptoms. Score 0 1 2 3 4 5 6 7 8
1st hour Nausea Nausea — Nausea Vomiting Vomiting Vomiting
1—6 hours
Nausea Nausea Vomiting Vomiting — Nausea Vomiting
(c) Late nausea is more distressing than that occurring within the first hour of the end of the operation, as this may be forgotten. The results obtained with this scoring scheme can be analyzed by the x2 method or the ridit analysis and examples of the use of the latter will be given later. OBSERVATIONS WITH THE METHOD
These apply only to the findings of the authors working in one hospital unit, but they illustrate some of the important points which have to be considered in studies of this nature. Results obtained independently by each of the three authors in series of fifty patients using a standard anaesthetic technique (methohexitone, nitrous oxide and oxygen, preceded by pethidine and atropine pre-operatively) were compared and no difference was found between three series. Pooling of the individual results was therefore justified. A detailed study was made of the importance of the duration of anaesthesia and the nature of the operation (D & C and C) and this is reported in the appendix. It shows that each series of cases should ideally contain equal numbers of both operations, or if this is not possible the series should be limited to one or other operation and only compared with another series based on the same operation. The average duration of anaesthesia in each series should be calculated and no comparisons should be made between two series differing markedly in this respect. Table II shows the findings obtained in four series, each of 200 cases (half D & C, and half C) using two anaesthetics and two forms of premedication (atropine 0.6 mg, with and without pethidine 100 mg). The average duration of anaesthesia was significantly different (t = 2.52; P<0.02) in the two series premedicated with pethidine-atropine, but there was no difference between any of the other series. Table III shows the probability levels of difference (obtained with the x2 test) between the four groups of patients of table II and demonstrates the possibilities offered by this method of study. It can be concluded that the addition of pethidine 100 mg to the premedication increases the incidence of postoperative emetic symptoms, this effect being more marked with methohexi-
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importance of this has been stressed by Riding (1960) and failure to record the occurrence of vomiting in the unconscious subject may explain the low incidence noted in some published reports. The incidence of emetic symptoms with each form of premedication is thus available as: (a) that occurring during the first hour after operation; (b) that occurring between 1 and 6 hours after operation; (c) the total incidence during the first 6 postoperative hours with vomiting again being recorded in preference to nausea where both symptoms occurred.
529
530
BRITISH JOURNAL OF ANAESTHESIA TABLE II
Incidence of emetic symptoms and average duration of anaesthesia in four series, each of'200 cases.
Anaesthesia
Atropine
9-36+0-276
24
PethidineAtropine
9-76±0-123
Methohexitone
Atropine PethidineAtropine
0—1
1—6
0—6
—
V
N
—
V
N
—
8
168
10
6
184
28
12
160
34
18
148
32
14
154
44
26
130
9-28 ±0-296
24
20
156
20
14
166
36
26
138
8-60+.0-248
40
30
130
44
32
124
66
36
98
V = vomiting.
N
N = nausea.
— = no emetic symptoms.
TABLE III
Probabilities that the difference in the incidence of total emetic symptoms {vomiting and nausea) between series of cases {table II) which differed only in one constituent of their medication, is due to chance. (The conventional minimal level of statistical significance is 005 (1 in 20) but a 001 (1 in 100) level would probably be necessary for a clinical significance.) Hours after the end of operation Variable factors
Constant factors 0—1
1—6
0—6
Premedication Atropine v. Pethidine-Atropine
Anaesthesia Thiopentone Methohexitone Total of above
002 001 0-01
0001 0001 0001
0-001 0001 0001
Anaesthesia Thiopentone v. Methohexitone
Premedication Atropine Pethidine-Atropine Total of above
0-20 010
001 001 0001
002 0001 0001
tone than with thiopentone and also becoming more evident between 1 and 6 hours after the end of operation. It also shows that it is not justifiable to pool indiscriminately the results obtained with two different barbiturates, particularly when an opiate is used for premedication. It is outside the scope of the present paper to offer suggestions as to the cause of this important finding. It is instructive to compare these findings with those obtained from the same patients using the scoring scheme (table I) and the ridit analysis technique. Figure 1 shows four possible uses of ridit analysis. In the left half of the diagram the atropine series is taken as the "identified distri-
002
bution" and the average ridit for the pethidineatropine series is calculated relative to this. In the right half the two series are pooled to form the identified distribution and the ridit for the two individual series calculated relative to the total series. The upper part of the figure deals with the total cases (scores 0 to 8), while the lower part deals only with the patients who were sick after operation (scores 1 to 8). This figure gives the mean ridit as 95 per cent confidence limits for each series; a lack of overlap between two series thus represents a significant difference (P<0.05). The findings of this study are as follows: (a) The incidence of postoperative emetic signs and symptoms was significantly greater in
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V
Premedication
Thiopentone
Hours after 1 he end of operation
Average duration of anaesthesia (min)
531
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA—
patients premedicated with pethidine-atropine as compared with those who received atropine alone. (b) The severity of the sickness in patients who exhibited emetic symptoms did not vary significantly with the form of premedication, although it was consistently less in those who did not receive pethidine. (c) Withmethohexitone, nitrous oxide and oxygen anaesthesia, patients who received atropine were significantly less sick after operation and those who were given pethidine-atropine showed a significantly greater increase in frequency and severity of emetic symptoms than the total series of cases. In other words,
While the method of assessment described was evolved to study the effects of drugs given before anaesthesia, it can be used (within certain limits) to compare the incidence and severity of emetic symptoms following different anaesthetic techniques. The information obtained in such studies would be limited in its application because of the brevity of the anaesthesia and the small number of techniques which can be justifiably used for the simple operation of uterine curettage. It is obvious that in such investigations the premedication should be kept constant and from the data in table II it would appear that this should be limited to atropine only.
ATROPINE
SERIES
AVERAGE RIDIT. •5 -6
DISTRIBUTION TOTAL
AVERAGE •5
HJH
pooled cases.
1
atropine premedication.
I
SERIES RIDIT. 6
|||[|[[|[|||
I
COMMENT
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pethidine-atropine premedication. indicates mean ridit of score and 95 per cent confidence limits are indicated by width of bands. Failure of two 95 per cent confidence limits to overlap shows a significant difference between two ridit scores. FIG. 1 Ridit analysis of the incidence of postoperative emetic symptoms assessed by the scoring system described in the text. (For details of cases and symptoms see table II.)
after pethidine premedication, in those patients who were sick, the severity was also more marked. This did not apply when thiopentone was used. It is usual only to compare the average ridit of two series of cases, but the comparison of individual series with the pooled total may be of value when the relative merits of a variety of anti-emetic drugs is being studied. The use of the ridit analysis for data obtained from sick patients only is limited by the small numbers of these, as compared with the total series, and hence the greater range of the 95 per cent confidence limits. However, it may be of value in detecting the effects of a very short acting anti-emetic drug; the total 6-hour incidence may be similar to that in the control series, but the score would be lower in the "sick patients" Unless the total incidence of emetic symptoms is fairly high, this might not be detected, using the total cases in the series. It can thus be seen that there is close agreement with the results obtained by the two methods of analysis. Each has its advantages and disadvantages. With the x2 method, it may only be feasible to compare the total incidence of emetic symptoms and it may be difficult to get an overall picture of the effect of a particular form of premedication. On the other hand, while the ridit will give the overall picture, it is difficult to detect where the difference between two drugs lies. Thus both give complementary data and it is recommended that, where possible, both be used for each study.
IDENTIFIED
BRITISH JOURNAL OF ANAESTHESIA
532 APPENDIX THE INFLUENCE OF THE DURATION OF ANAESTHESIA AND THE NATURE OF THE OPERATION ON THE INCIDENCE OF POSTOPERATIVE EMETIC SYMPTOMS
TABLE IV
Relation of duration of anaesthesia to the percentage incidence of emetic symptoms in the four series of cases of figure 2. Hours after the end of operation Series Methohexitone (A)
Duration of anaesthesia (min)
—
V
—
V
N
—
86
11
12
77
9 78
28
12
60
N
11
85
7
8—11
20
9
71
13
14
2
84
7
7
86
19
2
79
—7
17
6
77
20
17
63
27
15
58
8—11
20
25
55
20
18
62
32
25
43
27
23
50
18
23
59
32
23
45
—7
13
0
87
5
0
95
13
0
87
8—11
11
5
84
6
3
91
15
7
78
12
4
84
2
6
92
12
10
78
—7
15
7
78
10
8
82
16
10
74
8—11
19
5
76
18
4
78
24
9
67
21
15
64
21
10
69
28
21
51
12+ Thiopentone (P-A)
N
4
12 + Thiopentone (A)
V
0—6
1—6
—7
12+ Methohexitone (P-A)
0—1
12+
7
A = atropine premedication; P-A = pethidine-atropine premedication.
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Riding (1960) observed that patients undergoing dilatation and curettage (D & C) showed a higher incidence of emetic symptoms than those in whom the retained products of conception were removed without prior dilatation of the cervix (C). It has also been shown by Bodman, Morton and Thomas (1960) that as the duration of nitrous oxide and oxygen anaesthesia increased so did the frequency of vomiting during the first 15 minutes after operation. It seems that these two independent observations may be related since the operation of curettage alone can be expected to take less time than dilatation and curettage. Irrespective of this, they must be studied in detail in view of their importance in trials of anti-emetic drugs. The data to be presented applies only to the work of one team of gynaecologists and anaesthetists, but the number of observations analyzed is so great that the trends shown in this study are likely to have a wide application. Table IV show the incidence of postoperative emetic symptoms, related to the duration of anaesthesia in the four series (each of 200 cases) discussed previously (table II). (The divisions of the
time intervals of duration of anaesthesia were chosen so as to give a reasonably similar number of patients in each group.) It can be seen that the increase in emetic symptoms with increasing duration of anaesthesia only applies during the first hour after the end of the operation. In three of the four series studied, emetic symptoms occurred significantly more frequently (P<0.05) when anaesthesia lasted 12 minutes and more, as compared with those where the duration was 7 minutes and under. An important finding was that emetic symptoms occurred very rarely in cases lasting under 5 minutes and were very common when the duration of anaesthesia exceeded 14 minutes, particularly when pethidine was used as premedication. In each of these series the average duration of anaesthesia in the D & C cases was slightly greater than in the C cases, but the difference was not statistically significant. Emetic symptoms were consistently more frequent in the former series, but only in one instance did the difference in incidence between the two operative procedures reach the 5 per cent level of significance. Data from twenty-two series of cases—each consisting of at least fifty patients and composed of equal numbers of D & C and C operations—was analyzed to throw further light on the relationship between the nature of the operative procedure and the occurrence of postoperation emetic symptoms. In table V these are grouped under the intravenous
533
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA—HI TABLE V
Details of emetic sequelae and duration of anaesthesia in series of cases in whom the difference between the two operative procedures is studied.
Anaesthetic
No. of cases
Operation
545
D &C
8-96
54 54 437
67 72 406
106 91 348
C
8-65
58 39 448
53 60 432
87 73 385
D&C
10-27
44 24 270
43 30 265
64 46 228
C
9-24
36 23 279
31 23 284
50 33 255
D&C
7-28
36 45 79
19 20 111
47 28 75
C
6-35
32 24 94
13 13 124
41 20 89
D&C
915
134 123 766
129 122 782
217 169 647
C
8-63
126 86 821
97 96 840
178 126 729
Methohexitone
338
G.29.505
150
Total
1033
N = nausea.
0—1
V
— = no symptoms.
1—6
N —
V
0—6
N —
D & C = dilatation and curettage.
V
C = curettage alone.
TABLE VI
Levels of significance between dilatation and curettage (D & C) cases and curettage alone (C) cases. (Data given in table V.) Duration Hours after the end of operation
Methohexitone Thiopentone G.29.505 Total
anaesthesia
0—1
1—6
0—6
0-20>P>010 P<0001 P<0001
N.S. N.S. 0-20>P>010
010>P>005 P<001 010>P>005
P<005 P<005' 010>P>005
P<0001
P<001*
P<0-01*
P<001
*df = 2. Vomiting and nausea were analyzed separately. In other series df = 1 and total emetic symptoms were pooled TABLE VII
Distribution of the duration of anaesthesia with the two operative procedures. Duration of anaesthesia (min) Operation Anaesthetic —5 6—9 10—13 14+ Methohexitone
D&C C
61 127
280 239
142 126
62 53
Thiopentone
D&C C
24 63
144 143
111 82
59 50
G.29.505
D&C C
27 43
74 72
38 31
11 4
D&C C
11 23
49 44
27 23
13 10
Total (%)
N —
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Thiopentone
V = vomiting.
Hours after the end of operation
Average duration (min)
BRITISH JOURNAL OF ANAESTHESIA
534
REFERENCES
M
I
G
total
D & C cases (identified distribution). I
C cases.
M = Methohexitone anaesthesia. T = Thiopentone anaesthesia. G = G29.505 anaesthesia. FIG. 2 Average ridit of postoperative emetic scores (table I) in the series of cases outlined in tables V, VI, and VII. agent used for anaesthesia* and table VI gives the level of significance of the difference of the duration of anaesthesia and frequency of emetic symptoms between the two operative procedures. The result of ridit analysis of the severity of emetic symptoms (using the scoring scheme described previously) is shown in figure 2. In this the C cases are compared with the D & C patients, who form the "identified distribution". In the light of a previous statement the difference in duration of anaesthesia between the two procedures assumes even greater significance on examination of table VII. It is obvious from this study that the differences between both the duration of anaesthesia, and the incidence of postoperative emetic symptoms, with the operations of dilatation and curettage and curettage alone, are of sufficient magnitude to be important in a clinical study of postoperative vomiting. It seems very likely that the greater frequency of emetic sequelae with the dilatation and curettage operation is the result of the longer duration of anaesthesia required for this procedure. ACKNOWLEDGMENTS
The authors are indebted to Dr. J. E. Riding for pointing out the potential use of dilatation and curettage cases for these studies and for his continued advice on various aspects of this work; to Drs. Bross and Belville for their help with the ridit analysis; and the gynaecological department of Musgrave Park Hospital, Balmoral, for providing facilities for the investigations. *A large number of pre-operative drugs were employed in these series and space does not permit a full description of each. Exact details can be obtained on request from the authors.
Adriani, J., Summers, F. W., and Antony, S. O. (1961). Is the prophylactic use of anti-emetics in surgical patients justified? /. Amer. med. Ass., 175, 666. Armer, A. L. (1952). The control of postoperative nausea with the use of dimenhydrinate. /. oral. Surg., 10, 225. Belville, J. W., Bross, I. D. J., and Howland, W. C. (1959a). A method for the clinical evaluation of anti-emetic agents. Anesthesiology, 20, 753. (1959b). The anti-emetic efficacy of cyclizine (Marezine) and trifiupromazine (Vesprin). Anesthesiology, 20, 761. (1960). Postoperative nausea and vomiting. IV: Factors relating to postoperative nausea and vomiting. Anesthesiology, 21, 186. Howland, W. S., and Bross, I. D. J. (1960). Postoperative nausea and vomiting. Ill: Evaluation of the anti-emetic drugs fluphenazine (Prolixin) and promethazine (Phenergan) and comparison with trifiupromazine (Vesprin) and cyclizine (Marezine). J. Amer. med. Ass., 172, 1488. Bodman, R. L., Morton, H. J. V., and Thomas, E. T. (1960). Vomiting in outpatients after nitrous oxide anaesthesia. Brit. med. J., 1, 1327. Boulton, T. B. (1955). Oral chlorpromazine hydrochloride: A clinical trial in thoracic surgery. Anaesthesia, 10, 233. Burtles, R., and Peckett, B. W. (1957). Postoperative vomiting: some factors affecting its incidence. Brit. J. Anaesth., 29, 114. Comroe, J. H., and Dripps, R. D. (1948). Reactions to morphine in ambulatory and bed patients. Surg. Cynec. Obstet., 87, 221. Cook, B. E. (1931). Postoperative vomiting. Lancet, 1, 860. Davies, R. M. (1941). Some factors affecting the incidence of post-anaesthetic vomiting. Brit med J., 2, 578.
Dent, S. J., Ramachandra, V., and Stephen, C. R. (1955). Postoperative vomiting; incidence, analysis and therapeutic measures in 3,000 patients. Anesthesiology, 16, 564. 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. (1962a). Studies of drugs given before anaesthesia. I: A method of preoperative assessment. Brit. J. Anaesth., 34, 458. (1962b). Studies of drugs given before anaesthesia. II: A method for assessing their influence on the course of anaesthesia Brit. J. Anaesth., 34, 523. Gillespie, N. A. (1950). Simplicity in anaesthesia. Brit. J. Anaesth.. 22, 192. Harris, T. A. B. (1951). The Mode of Action of Anaesthetics. Edinburgh and London: E. and S. Livingstone.
Downloaded from http://bja.oxfordjournals.org/ at University of Edinburgh on June 22, 2015
^H
T
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA—III
Wolfe, W. B. (1952). Use of Dramamine in prevention of postoperative nausea and vomiting. Ann. Surg., 136, 261.
SOMMAIRE
Pour que l'etude des effets de substances administre'es avant une operation chirurgicale soit complete il faut etudier incidence et degre de gravite des symptomes eme'tiques postope'ratoires que l'on peut attribuer a leur emploi. Les auteurs fournissent la description d'une etude semblable. En limitant les observations des effets a des patients anesthesias k l'aide d'une technique standardised pendant des interventions gynecologiques mineures, reduit, autant que cela est cliniquement possible, les facteurs variables susceptibles "d'invalider" (ruiner) les constatations. Les auteurs indiquent un systeme d'appreciation numerique pour indiquer les divers degrtis de gravite des signes de vomissement et des symptomes. 11s insistent sur Pimportance du choix des anesth^siques selon nature et duree de l'operation.
ZUSAMMENFASSUNG
Eine umfassende Untersuchung der Wirkungen von Medikamenten, die vor einer Operation gegeben werden, erfordern eine Studie iiber die Haufigkeit und Schwere postoperativer Brech-Symptome, die auf ihre Anwendung zuriickgefuhrt werden konnten. Eine Methode fiir eine solche Studie wird beschrieben. Die Begrenzung der Beobachtungen auf Patienten, die mit einer iiblichen Narkosetechnik fiir kleinere gynakologische Eingriffe vorbereitet wurden, vermindert, soweit dies klinisch moglich ist, die variablen Faktoren, die den Wert der Befunde beeintrachtigen konnten. Ein Punktsystem zur Abstufung der Schwere der Anzeichen und Symptome des Erbrechens wird beschrieben und die Bedeutung der Auswahl des Narkosemittels und die Art und Dauer der Operation besprochen.
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Jaquenoud, P., and Mercier, T. (1951). Prevention of postoperative vomiting by antihistamines. Presse. med., 59, 1662. Anesth. et Analg., 8, 724. Kaye, G. (1936). Sequelae of anaesthesia. Brit. J. Anaesth., 13, 157. Knapp, M. R., and Beecher, H. K. (1956). Postanesthetic nausea and vomiting: evaluation of the anti-emetic drugs dimenhydrinate (Dramamine), chlorpromazine and pentobarbital sodium. /. Amer. med. Ass., 160, 376. Moore, D. C , Bridenbaugh, L. D., Green, J. C , Piccioni, V. F., Adams, P. A., and Linstrom, C. A. (1955). Intramuscular use of dimenhydrinate (Dramamine) to control postoperative vomiting. /. Amer. med. Ass., 159, 1342. — Piccioni, V. F., Adams, P. A., and Linstrom, C. A. (1956). Control of postoperative vomiting with Marezine: a double blind study. Anesthesiology, 17, 690. van Acheren, E. G., and Cole, F. V. (1958). Control of postoperative vomiting with perphenazine (Trilafon): a double blind study. Anesthesiology, 19, 72. Moore, J., and Dundee, J. W. (1961). Promethazine: its influence on the course of thiopentone and methohexital anaesthesia. Anaesthesia, 16, 61. Phillips, O. E., Nelson, A. T., Lyons, W. B., Graff, T. D., and Frazier, T. M. (1958). The effect of Trilafon on postanaesthetic nausea, retching and vomiting. Curr. Res. Anesth., 37, 341. Riding, J. E. (1960). Postoperative vomiting. Proc. roy. Soc. Med., 53, 671. Scurr, C. F., and Robbie, D. S. (1958). Trials of perphenazine in the prevention of postoperative vomiting. Brit. med. J., 1, 922. Smessaert, A., Schehr, C. A., and Artusio, J. F., jr. (1959). Nausea and vomiting in the immediate postanesthetic period. /. Amer. med. Ass., 170, 2072. Smith, G. F. R. (1934). Postoperative vomiting. Brit. J. Anaesth., 11, 132. Wangeman, C P., and Hawk, M. H. (1942). The effects of morphine, atropine and scopolamine on human subjects. Anesthesiology, 3, 24.
535
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA HI: A METHOD FOR THE STUDYING OF THEIR EFFECTS ON POSTOPERATIVE VOMITING AND NAUSEA BY
JOHN W. DUNDEE, ROBERT M. NICHOLL AND JAMES MOORE
Department of Anaesthetics, The Queen's University of Belfast, Northern Ireland SUMMARY
In the two previous papers in this series, the need mentioned (Smessaert, Schehr and Artusio, 1959; for a comprehensive study of the drugs given Belville, Bross and Howland, 1959a, b, 1960; before anaesthesia was stressed and methods were Belville, Howland and Bross, 1960). described for investigating their effects in the preCHOICE OF PATIENTS AND OPERATION operative period and their influence on the course of anaesthesia (Dundee, Moore and Nicholl, In addition to the pre-anaesthetic medication 1962a, b). This publication describes a method there is suggestive, if not always conclusive, for studying the incidence and severity of post- evidence that other factors influence the degree operative emetic symptoms which follow their and severity of postoperative emetic symptoms. use. These include the sex of the patient (Knapp and It is improbable that drugs which cause a high Beecher, 1956; Burtles and Peckett, 1957; Scurr incidence of other sequelae, such as hypotension, and Robbie, 1958), the nature and duration of are likely to come into clinical use. However, the operative procedure (Davies, 1941; Dent, there is convincing evidence to incriminate the Ramachandra and Stephen, 1955; Bodman, pre-operative use of the potent analgesics as a Morton and Thomas, 1960) and the anaesthetic major factor in causing postoperative vomiting technique employed (Cook, 1931; Gillespie, and nausea under certain circumstances ( J a 1 u e - 1950; Wolfe, 1952). Because these factors are noud and Mercier, 1951; Phillips et al., 1958; of unknown importance it is essential to control Riding, 1960). This undesirable side effect of as many variables as possible within the limits their action has been very inadequately studied, of clinical practice. This can be achieved by but is receiving more attention since the intro- limiting observations to females operated on for duction of the anti-emetic drugs. The lack of dilatation and curettage under a standard anaesappreciation of the importance of premedication thetic technique of a barbiturate, nitrous oxide as a factor influencing postoperative vomiting is and oxygen as described by Dundee and Moore shown by the many publications on the emetic (1961a, b, c) and Moore and Dundee (1961). sequelae of anaesthesia in which this factor is The significance of the variations in the duraeither ignored (Cook, 1931; Kaye, 1936; Adriani, tion of anaesthesia in a large series of cases will Summers and Antony, 1961), or else the nature be discussed later, as will the significance of the of the drug given before anaesthesia is not even difference in procedure between patients under527
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A complete study of the effects of drugs given before operation necessitates an investigation of the incidence and severity of postoperative emetic symptoms which might be attributable to their use. A method of such a study is described. The limitation of observations to patients anaesthetized with a standard anaesthetic technique for minor gynaecological operations reduces, as far as is clinically possible, the variable factors which could invalidate the findings. A scoring system for grading the severity of emetic signs and symptoms is described, and the importance of the choice of anaesthetic and the nature and duration of the operation is discussed.
528
These variables must be eliminated to obtain reliable data and the findings to be reported by the authors were all obtained in one hospital unit in which it was possible to ensure uniformity in regard to these factors. OBSERVATIONS
These are all made during the first 6 hours after the end of the operation, for although Wangeman and Hawk (1942) and Comroe and Dripps (1948) found that the effects of the potent analgesics may last beyond this time, it is unlikely that vomiting resulting from their administration will start for the first time about 7 hours or more after their injection. Furthermore, patients' habits as regards meals and ambulation may play a part in the incidence of vomiting and nausea, if this time is exceeded. This method will therefore give a time incidence of postoperative emetic symptoms which can be attributed to premedication, but the 6-hour time limit on observations must be remembered when considering their severity. Observations are limited to those which can be easily carried out by a single anaesthetist on a large number of patients, and this excluded a study of the total number of emetic episodes or the volume of the vomitus, as carried out by Boulton (1955) and Moore et al. (1955, 1956, 1958). Boulton has stressed the importance of recording the number of times the patient vomited when assessing the efficacy of anti-emetic drugs. He points out that "emergence" vomit of secretions collected in the stomach and oesophagus during operation is a frequent occurrence, which will not be affected by an anti-emetic drug, but such a drug will be expected to reduce the incidence of further episodes of vomiting. While this may apply to prolonged operations it is not likely to be an important factor in the present studies. All patients are seen by one of the authors at the end of the first hour after operation and as near as possible to 5 hours later. Emetic symptoms are classed as "vomiting" (which includes retching) or "nausea", but when both occurred this is recorded as "vomiting". Vomiting or retching occurring at the end of anaesthesia is noted, irrespective of whether consciousness has returned or not. The
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going cervical dilatation and uterine curettage (D & C) and those having curettage without preliminary dilatation of the cervix (C) (as in incomplete abortion). The brevity of this operation ensures that the effects of the drugs used in premedication persist into the postoperative period, and the incidence and severity of emetic symptoms can be related to the drugs given before anaesthesia. Patients also recover rapidly from the short anaesthesia and episodes of vomiting in an unconscious patient are unlikely to escape notice. Emergence vomiting is frequently ignored in studies of this nature, leading to an erroneously low incidence of emetic symptoms. Analgesics are not required after operation and so the effect of postoperative drugs does not vitiate the findings. Furthermore, large numbers of subjects are readily available and the factors of unknown importance which are outside the control of the anaesthetist, such as a history of motion sickness (Smith, 1934; Armer, 1952; Burtles and Peckett, 1957), can be minimized. Limitation of the choice of subjects to those in good physical condition (Dundee, Moore and Nicholl, 1962a) excludes patients with ketosis which has been incriminated as an aetiological factor in postoperative vomiting by Harris (1951) and Jaquenoud and Mercier (1951). It also ensures that they fall within certain age limits, which Burtles and Peckett have shown may well be another important consideration. Much has been written about the importance of the skill of the anaesthetist as a factor to be considered when studying postoperative emetic symptoms, but there are no specific data to suggest that this is an important factor. In the present studies, all anaesthetics have been given by the authors or by junior colleagues working under their direct supervision. The importance in having all patients in one hospital unit has not been adequately stressed in the published literature on this topic. The routine as regards time of operation, postoperative ambulation, visiting hours and meal times varies from hospital to hospital and ward to ward, and patients who are left alone for several hours after operation are less likely to be sick than those who are disturbed by visitors or given a meal or drinks early in the postoperative period.
BRITISH JOURNAL OF ANAESTHESIA
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA—III
ANALYSIS OF FINDINGS
The incidence of symptoms in the three time periods outlined above can be analyzed using the standard x2 test. There are obvious limitations to the value of this procedure, because the overall severity of the symptoms is not demonstrated. In addition to this a scoring scheme has been devised, based on that used by Belville, Brass and Howland (1959a). This combines the findings obtained during the first hour after the end of operation with those in the later period and thus gives a better overall picture of the severity of the emetic symptoms. The scoring scheme is shown in table I and is based on certain assumptions which seem valid to the authors. (a) Vomiting is more distressing and dangerous than nausea. (b) Early (0-1 hour) vomiting is more dangerous than late (1-6 hours) vomiting. TABLE I
Scheme for assessing severity of postoperative emetic symptoms. Score 0 1 2 3 4 5 6 7 8
1st hour Nausea Nausea — Nausea Vomiting Vomiting Vomiting
1—6 hours
Nausea Nausea Vomiting Vomiting — Nausea Vomiting
(c) Late nausea is more distressing than that occurring within the first hour of the end of the operation, as this may be forgotten. The results obtained with this scoring scheme can be analyzed by the x2 method or the ridit analysis and examples of the use of the latter will be given later. OBSERVATIONS WITH THE METHOD
These apply only to the findings of the authors working in one hospital unit, but they illustrate some of the important points which have to be considered in studies of this nature. Results obtained independently by each of the three authors in series of fifty patients using a standard anaesthetic technique (methohexitone, nitrous oxide and oxygen, preceded by pethidine and atropine pre-operatively) were compared and no difference was found between three series. Pooling of the individual results was therefore justified. A detailed study was made of the importance of the duration of anaesthesia and the nature of the operation (D & C and C) and this is reported in the appendix. It shows that each series of cases should ideally contain equal numbers of both operations, or if this is not possible the series should be limited to one or other operation and only compared with another series based on the same operation. The average duration of anaesthesia in each series should be calculated and no comparisons should be made between two series differing markedly in this respect. Table II shows the findings obtained in four series, each of 200 cases (half D & C, and half C) using two anaesthetics and two forms of premedication (atropine 0.6 mg, with and without pethidine 100 mg). The average duration of anaesthesia was significantly different (t = 2.52; P<0.02) in the two series premedicated with pethidine-atropine, but there was no difference between any of the other series. Table III shows the probability levels of difference (obtained with the x2 test) between the four groups of patients of table II and demonstrates the possibilities offered by this method of study. It can be concluded that the addition of pethidine 100 mg to the premedication increases the incidence of postoperative emetic symptoms, this effect being more marked with methohexi-
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importance of this has been stressed by Riding (1960) and failure to record the occurrence of vomiting in the unconscious subject may explain the low incidence noted in some published reports. The incidence of emetic symptoms with each form of premedication is thus available as: (a) that occurring during the first hour after operation; (b) that occurring between 1 and 6 hours after operation; (c) the total incidence during the first 6 postoperative hours with vomiting again being recorded in preference to nausea where both symptoms occurred.
529
530
BRITISH JOURNAL OF ANAESTHESIA TABLE II
Incidence of emetic symptoms and average duration of anaesthesia in four series, each of'200 cases.
Anaesthesia
Atropine
9-36+0-276
24
PethidineAtropine
9-76±0-123
Methohexitone
Atropine PethidineAtropine
0—1
1—6
0—6
—
V
N
—
V
N
—
8
168
10
6
184
28
12
160
34
18
148
32
14
154
44
26
130
9-28 ±0-296
24
20
156
20
14
166
36
26
138
8-60+.0-248
40
30
130
44
32
124
66
36
98
V = vomiting.
N
N = nausea.
— = no emetic symptoms.
TABLE III
Probabilities that the difference in the incidence of total emetic symptoms {vomiting and nausea) between series of cases {table II) which differed only in one constituent of their medication, is due to chance. (The conventional minimal level of statistical significance is 005 (1 in 20) but a 001 (1 in 100) level would probably be necessary for a clinical significance.) Hours after the end of operation Variable factors
Constant factors 0—1
1—6
0—6
Premedication Atropine v. Pethidine-Atropine
Anaesthesia Thiopentone Methohexitone Total of above
002 001 0-01
0001 0001 0001
0-001 0001 0001
Anaesthesia Thiopentone v. Methohexitone
Premedication Atropine Pethidine-Atropine Total of above
0-20 010
001 001 0001
002 0001 0001
tone than with thiopentone and also becoming more evident between 1 and 6 hours after the end of operation. It also shows that it is not justifiable to pool indiscriminately the results obtained with two different barbiturates, particularly when an opiate is used for premedication. It is outside the scope of the present paper to offer suggestions as to the cause of this important finding. It is instructive to compare these findings with those obtained from the same patients using the scoring scheme (table I) and the ridit analysis technique. Figure 1 shows four possible uses of ridit analysis. In the left half of the diagram the atropine series is taken as the "identified distri-
002
bution" and the average ridit for the pethidineatropine series is calculated relative to this. In the right half the two series are pooled to form the identified distribution and the ridit for the two individual series calculated relative to the total series. The upper part of the figure deals with the total cases (scores 0 to 8), while the lower part deals only with the patients who were sick after operation (scores 1 to 8). This figure gives the mean ridit as 95 per cent confidence limits for each series; a lack of overlap between two series thus represents a significant difference (P<0.05). The findings of this study are as follows: (a) The incidence of postoperative emetic signs and symptoms was significantly greater in
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V
Premedication
Thiopentone
Hours after 1 he end of operation
Average duration of anaesthesia (min)
531
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA—
patients premedicated with pethidine-atropine as compared with those who received atropine alone. (b) The severity of the sickness in patients who exhibited emetic symptoms did not vary significantly with the form of premedication, although it was consistently less in those who did not receive pethidine. (c) Withmethohexitone, nitrous oxide and oxygen anaesthesia, patients who received atropine were significantly less sick after operation and those who were given pethidine-atropine showed a significantly greater increase in frequency and severity of emetic symptoms than the total series of cases. In other words,
While the method of assessment described was evolved to study the effects of drugs given before anaesthesia, it can be used (within certain limits) to compare the incidence and severity of emetic symptoms following different anaesthetic techniques. The information obtained in such studies would be limited in its application because of the brevity of the anaesthesia and the small number of techniques which can be justifiably used for the simple operation of uterine curettage. It is obvious that in such investigations the premedication should be kept constant and from the data in table II it would appear that this should be limited to atropine only.
ATROPINE
SERIES
AVERAGE RIDIT. •5 -6
DISTRIBUTION TOTAL
AVERAGE •5
HJH
pooled cases.
1
atropine premedication.
I
SERIES RIDIT. 6
|||[|[[|[|||
I
COMMENT
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pethidine-atropine premedication. indicates mean ridit of score and 95 per cent confidence limits are indicated by width of bands. Failure of two 95 per cent confidence limits to overlap shows a significant difference between two ridit scores. FIG. 1 Ridit analysis of the incidence of postoperative emetic symptoms assessed by the scoring system described in the text. (For details of cases and symptoms see table II.)
after pethidine premedication, in those patients who were sick, the severity was also more marked. This did not apply when thiopentone was used. It is usual only to compare the average ridit of two series of cases, but the comparison of individual series with the pooled total may be of value when the relative merits of a variety of anti-emetic drugs is being studied. The use of the ridit analysis for data obtained from sick patients only is limited by the small numbers of these, as compared with the total series, and hence the greater range of the 95 per cent confidence limits. However, it may be of value in detecting the effects of a very short acting anti-emetic drug; the total 6-hour incidence may be similar to that in the control series, but the score would be lower in the "sick patients" Unless the total incidence of emetic symptoms is fairly high, this might not be detected, using the total cases in the series. It can thus be seen that there is close agreement with the results obtained by the two methods of analysis. Each has its advantages and disadvantages. With the x2 method, it may only be feasible to compare the total incidence of emetic symptoms and it may be difficult to get an overall picture of the effect of a particular form of premedication. On the other hand, while the ridit will give the overall picture, it is difficult to detect where the difference between two drugs lies. Thus both give complementary data and it is recommended that, where possible, both be used for each study.
IDENTIFIED
BRITISH JOURNAL OF ANAESTHESIA
532 APPENDIX THE INFLUENCE OF THE DURATION OF ANAESTHESIA AND THE NATURE OF THE OPERATION ON THE INCIDENCE OF POSTOPERATIVE EMETIC SYMPTOMS
TABLE IV
Relation of duration of anaesthesia to the percentage incidence of emetic symptoms in the four series of cases of figure 2. Hours after the end of operation Series Methohexitone (A)
Duration of anaesthesia (min)
—
V
—
V
N
—
86
11
12
77
9 78
28
12
60
N
11
85
7
8—11
20
9
71
13
14
2
84
7
7
86
19
2
79
—7
17
6
77
20
17
63
27
15
58
8—11
20
25
55
20
18
62
32
25
43
27
23
50
18
23
59
32
23
45
—7
13
0
87
5
0
95
13
0
87
8—11
11
5
84
6
3
91
15
7
78
12
4
84
2
6
92
12
10
78
—7
15
7
78
10
8
82
16
10
74
8—11
19
5
76
18
4
78
24
9
67
21
15
64
21
10
69
28
21
51
12+ Thiopentone (P-A)
N
4
12 + Thiopentone (A)
V
0—6
1—6
—7
12+ Methohexitone (P-A)
0—1
12+
7
A = atropine premedication; P-A = pethidine-atropine premedication.
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Riding (1960) observed that patients undergoing dilatation and curettage (D & C) showed a higher incidence of emetic symptoms than those in whom the retained products of conception were removed without prior dilatation of the cervix (C). It has also been shown by Bodman, Morton and Thomas (1960) that as the duration of nitrous oxide and oxygen anaesthesia increased so did the frequency of vomiting during the first 15 minutes after operation. It seems that these two independent observations may be related since the operation of curettage alone can be expected to take less time than dilatation and curettage. Irrespective of this, they must be studied in detail in view of their importance in trials of anti-emetic drugs. The data to be presented applies only to the work of one team of gynaecologists and anaesthetists, but the number of observations analyzed is so great that the trends shown in this study are likely to have a wide application. Table IV show the incidence of postoperative emetic symptoms, related to the duration of anaesthesia in the four series (each of 200 cases) discussed previously (table II). (The divisions of the
time intervals of duration of anaesthesia were chosen so as to give a reasonably similar number of patients in each group.) It can be seen that the increase in emetic symptoms with increasing duration of anaesthesia only applies during the first hour after the end of the operation. In three of the four series studied, emetic symptoms occurred significantly more frequently (P<0.05) when anaesthesia lasted 12 minutes and more, as compared with those where the duration was 7 minutes and under. An important finding was that emetic symptoms occurred very rarely in cases lasting under 5 minutes and were very common when the duration of anaesthesia exceeded 14 minutes, particularly when pethidine was used as premedication. In each of these series the average duration of anaesthesia in the D & C cases was slightly greater than in the C cases, but the difference was not statistically significant. Emetic symptoms were consistently more frequent in the former series, but only in one instance did the difference in incidence between the two operative procedures reach the 5 per cent level of significance. Data from twenty-two series of cases—each consisting of at least fifty patients and composed of equal numbers of D & C and C operations—was analyzed to throw further light on the relationship between the nature of the operative procedure and the occurrence of postoperation emetic symptoms. In table V these are grouped under the intravenous
533
STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA—HI TABLE V
Details of emetic sequelae and duration of anaesthesia in series of cases in whom the difference between the two operative procedures is studied.
Anaesthetic
No. of cases
Operation
545
D &C
8-96
54 54 437
67 72 406
106 91 348
C
8-65
58 39 448
53 60 432
87 73 385
D&C
10-27
44 24 270
43 30 265
64 46 228
C
9-24
36 23 279
31 23 284
50 33 255
D&C
7-28
36 45 79
19 20 111
47 28 75
C
6-35
32 24 94
13 13 124
41 20 89
D&C
915
134 123 766
129 122 782
217 169 647
C
8-63
126 86 821
97 96 840
178 126 729
Methohexitone
338
G.29.505
150
Total
1033
N = nausea.
0—1
V
— = no symptoms.
1—6
N —
V
0—6
N —
D & C = dilatation and curettage.
V
C = curettage alone.
TABLE VI
Levels of significance between dilatation and curettage (D & C) cases and curettage alone (C) cases. (Data given in table V.) Duration Hours after the end of operation
Methohexitone Thiopentone G.29.505 Total
anaesthesia
0—1
1—6
0—6
0-20>P>010 P<0001 P<0001
N.S. N.S. 0-20>P>010
010>P>005 P<001 010>P>005
P<005 P<005' 010>P>005
P<0001
P<001*
P<0-01*
P<001
*df = 2. Vomiting and nausea were analyzed separately. In other series df = 1 and total emetic symptoms were pooled TABLE VII
Distribution of the duration of anaesthesia with the two operative procedures. Duration of anaesthesia (min) Operation Anaesthetic —5 6—9 10—13 14+ Methohexitone
D&C C
61 127
280 239
142 126
62 53
Thiopentone
D&C C
24 63
144 143
111 82
59 50
G.29.505
D&C C
27 43
74 72
38 31
11 4
D&C C
11 23
49 44
27 23
13 10
Total (%)
N —
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Thiopentone
V = vomiting.
Hours after the end of operation
Average duration (min)
BRITISH JOURNAL OF ANAESTHESIA
534
REFERENCES
M
I
G
total
D & C cases (identified distribution). I
C cases.
M = Methohexitone anaesthesia. T = Thiopentone anaesthesia. G = G29.505 anaesthesia. FIG. 2 Average ridit of postoperative emetic scores (table I) in the series of cases outlined in tables V, VI, and VII. agent used for anaesthesia* and table VI gives the level of significance of the difference of the duration of anaesthesia and frequency of emetic symptoms between the two operative procedures. The result of ridit analysis of the severity of emetic symptoms (using the scoring scheme described previously) is shown in figure 2. In this the C cases are compared with the D & C patients, who form the "identified distribution". In the light of a previous statement the difference in duration of anaesthesia between the two procedures assumes even greater significance on examination of table VII. It is obvious from this study that the differences between both the duration of anaesthesia, and the incidence of postoperative emetic symptoms, with the operations of dilatation and curettage and curettage alone, are of sufficient magnitude to be important in a clinical study of postoperative vomiting. It seems very likely that the greater frequency of emetic sequelae with the dilatation and curettage operation is the result of the longer duration of anaesthesia required for this procedure. ACKNOWLEDGMENTS
The authors are indebted to Dr. J. E. Riding for pointing out the potential use of dilatation and curettage cases for these studies and for his continued advice on various aspects of this work; to Drs. Bross and Belville for their help with the ridit analysis; and the gynaecological department of Musgrave Park Hospital, Balmoral, for providing facilities for the investigations. *A large number of pre-operative drugs were employed in these series and space does not permit a full description of each. Exact details can be obtained on request from the authors.
Adriani, J., Summers, F. W., and Antony, S. O. (1961). Is the prophylactic use of anti-emetics in surgical patients justified? /. Amer. med. Ass., 175, 666. Armer, A. L. (1952). The control of postoperative nausea with the use of dimenhydrinate. /. oral. Surg., 10, 225. Belville, J. W., Bross, I. D. J., and Howland, W. C. (1959a). A method for the clinical evaluation of anti-emetic agents. Anesthesiology, 20, 753. (1959b). The anti-emetic efficacy of cyclizine (Marezine) and trifiupromazine (Vesprin). Anesthesiology, 20, 761. (1960). Postoperative nausea and vomiting. IV: Factors relating to postoperative nausea and vomiting. Anesthesiology, 21, 186. Howland, W. S., and Bross, I. D. J. (1960). Postoperative nausea and vomiting. Ill: Evaluation of the anti-emetic drugs fluphenazine (Prolixin) and promethazine (Phenergan) and comparison with trifiupromazine (Vesprin) and cyclizine (Marezine). J. Amer. med. Ass., 172, 1488. Bodman, R. L., Morton, H. J. V., and Thomas, E. T. (1960). Vomiting in outpatients after nitrous oxide anaesthesia. Brit. med. J., 1, 1327. Boulton, T. B. (1955). Oral chlorpromazine hydrochloride: A clinical trial in thoracic surgery. Anaesthesia, 10, 233. Burtles, R., and Peckett, B. W. (1957). Postoperative vomiting: some factors affecting its incidence. Brit. J. Anaesth., 29, 114. Comroe, J. H., and Dripps, R. D. (1948). Reactions to morphine in ambulatory and bed patients. Surg. Cynec. Obstet., 87, 221. Cook, B. E. (1931). Postoperative vomiting. Lancet, 1, 860. Davies, R. M. (1941). Some factors affecting the incidence of post-anaesthetic vomiting. Brit med J., 2, 578.
Dent, S. J., Ramachandra, V., and Stephen, C. R. (1955). Postoperative vomiting; incidence, analysis and therapeutic measures in 3,000 patients. Anesthesiology, 16, 564. 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. (1962a). Studies of drugs given before anaesthesia. I: A method of preoperative assessment. Brit. J. Anaesth., 34, 458. (1962b). Studies of drugs given before anaesthesia. II: A method for assessing their influence on the course of anaesthesia Brit. J. Anaesth., 34, 523. Gillespie, N. A. (1950). Simplicity in anaesthesia. Brit. J. Anaesth.. 22, 192. Harris, T. A. B. (1951). The Mode of Action of Anaesthetics. Edinburgh and London: E. and S. Livingstone.
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STUDIES OF DRUGS GIVEN BEFORE ANAESTHESIA—III
Wolfe, W. B. (1952). Use of Dramamine in prevention of postoperative nausea and vomiting. Ann. Surg., 136, 261.
SOMMAIRE
Pour que l'etude des effets de substances administre'es avant une operation chirurgicale soit complete il faut etudier incidence et degre de gravite des symptomes eme'tiques postope'ratoires que l'on peut attribuer a leur emploi. Les auteurs fournissent la description d'une etude semblable. En limitant les observations des effets a des patients anesthesias k l'aide d'une technique standardised pendant des interventions gynecologiques mineures, reduit, autant que cela est cliniquement possible, les facteurs variables susceptibles "d'invalider" (ruiner) les constatations. Les auteurs indiquent un systeme d'appreciation numerique pour indiquer les divers degrtis de gravite des signes de vomissement et des symptomes. 11s insistent sur Pimportance du choix des anesth^siques selon nature et duree de l'operation.
ZUSAMMENFASSUNG
Eine umfassende Untersuchung der Wirkungen von Medikamenten, die vor einer Operation gegeben werden, erfordern eine Studie iiber die Haufigkeit und Schwere postoperativer Brech-Symptome, die auf ihre Anwendung zuriickgefuhrt werden konnten. Eine Methode fiir eine solche Studie wird beschrieben. Die Begrenzung der Beobachtungen auf Patienten, die mit einer iiblichen Narkosetechnik fiir kleinere gynakologische Eingriffe vorbereitet wurden, vermindert, soweit dies klinisch moglich ist, die variablen Faktoren, die den Wert der Befunde beeintrachtigen konnten. Ein Punktsystem zur Abstufung der Schwere der Anzeichen und Symptome des Erbrechens wird beschrieben und die Bedeutung der Auswahl des Narkosemittels und die Art und Dauer der Operation besprochen.
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Jaquenoud, P., and Mercier, T. (1951). Prevention of postoperative vomiting by antihistamines. Presse. med., 59, 1662. Anesth. et Analg., 8, 724. Kaye, G. (1936). Sequelae of anaesthesia. Brit. J. Anaesth., 13, 157. Knapp, M. R., and Beecher, H. K. (1956). Postanesthetic nausea and vomiting: evaluation of the anti-emetic drugs dimenhydrinate (Dramamine), chlorpromazine and pentobarbital sodium. /. Amer. med. Ass., 160, 376. Moore, D. C , Bridenbaugh, L. D., Green, J. C , Piccioni, V. F., Adams, P. A., and Linstrom, C. A. (1955). Intramuscular use of dimenhydrinate (Dramamine) to control postoperative vomiting. /. Amer. med. Ass., 159, 1342. — Piccioni, V. F., Adams, P. A., and Linstrom, C. A. (1956). Control of postoperative vomiting with Marezine: a double blind study. Anesthesiology, 17, 690. van Acheren, E. G., and Cole, F. V. (1958). Control of postoperative vomiting with perphenazine (Trilafon): a double blind study. Anesthesiology, 19, 72. Moore, J., and Dundee, J. W. (1961). Promethazine: its influence on the course of thiopentone and methohexital anaesthesia. Anaesthesia, 16, 61. Phillips, O. E., Nelson, A. T., Lyons, W. B., Graff, T. D., and Frazier, T. M. (1958). The effect of Trilafon on postanaesthetic nausea, retching and vomiting. Curr. Res. Anesth., 37, 341. Riding, J. E. (1960). Postoperative vomiting. Proc. roy. Soc. Med., 53, 671. Scurr, C. F., and Robbie, D. S. (1958). Trials of perphenazine in the prevention of postoperative vomiting. Brit. med. J., 1, 922. Smessaert, A., Schehr, C. A., and Artusio, J. F., jr. (1959). Nausea and vomiting in the immediate postanesthetic period. /. Amer. med. Ass., 170, 2072. Smith, G. F. R. (1934). Postoperative vomiting. Brit. J. Anaesth., 11, 132. Wangeman, C P., and Hawk, M. H. (1942). The effects of morphine, atropine and scopolamine on human subjects. Anesthesiology, 3, 24.
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