PENTAZOCINE AND PHENAZOCINE: A Double-Blind Comparison of Two Benzomorphan Derivatives in Postoperative Pain

Brit. J. Anaesth. (1966), 38, 345

PENTAZOCINE AND PHENAZOCINE A Double-Blind Comparison of Two Benzomorphan Derivatives in Postoperative Pain BY

J. P. CONAGHAN, M . JACOBSEN,* L. RAE AND J. N . WARD-McQuAID

Mansfield Group of Hospitals, Nottinghamshire, England SUMMARY

The analgesic effeas of intramuscular injections of 30 and 45 mg pentazocine (Win 20, 228) were compared with 2 and 3 mg phenazocine (Narphen) in 128 patients with pain following abdominal surgery. Well-matched pairs of patients were allocated randomly to drugs. Pain was assessed under double-blind conditions, patients' assessments of relief were noted and vital capacity measurements were made. Both drugs were efficient for the relief of postoperative pain and did not cause nausea or vomiting. On average, 38 mg Win 20,228 was analgesically equivalent to 2.6 mg phenazocine. Changes in vital capacity gave a good indication of postoperative pain relief after bodi upper and lower abdominal operations. These changes were found to be significantly correlated with vital capacity before injection. Large numbers of compounds have been synthetized in the search for an analgesic as effective as morphine but without the addiction liability of this standard drug, and with fewer side effects. Many benzomorphan derivatives have been included in the search. Phenazocine (Narphen, fig. 1) is an effective analgesic, and on a weight-forweight basis it is more potent than morphine. Estimates of doses equivalent to given doses of other analgesics have varied (Eckenhoff, 1959; Sadove, Schiffrin and Heller, 1959; Corbit and First, 1961; Jolly, 1962; Swerdlow, Starmer and Daw, 1964). Lasagna (1964) reviewed many of these trials and he concluded that 3 mg phenazocine by injection can substitute for 10 mg morphine as an analgesic; in equivalent analgesic doses phenazocine produces as much or more respiratory depression. Lasagna's conclusions are in close agreement with the findings of Houde and associates (1964). These workers conducted a carefully controlled clinical assay of phenazocine, from which they estimated it to be 3-4 times as potent as morphine as an analgesic, and 6.3 times as potent as morphine as a respiratory depressant. Early hopes that phenazocine would prove to be non-addictive have been disappointed. Fraser and Isbell (1960) found the drug to be a completely • Statistician, Bayer Products. Present address: Glaxo Laboratories Ltd., Ulverston, Lanes.

adequate substitute for morphine in addicted persons, and phenazocine is included among drugs liable to cause dependence in the list published by the World Health Organisation (Brit, med. J., 1964). N —R

CH, PHENAZOCINE:

PENTAZOCINE :

R=

—CH2CH

R = —CH2CH:C(CH3)2 1

FIG.

Pentazocine, also known as Win 20,228 (fig. 1), is a new benzomorphan derivative. In order to avoid confusion with phenazocine (Narphen) it will be referred to by its research number in this report. Pharmacological studies by Harris and Pierson (1964) showed Win 20,228 to be a weak antagonist of morphine. Fraser and Rosenberg (1964) describe it as having "definitely less addictiveness" than morphine. Keats and Telford

346

BRITISH JOURNAL OF ANAESTHESIA

(1964) compared the drug with morphine and saline in postoperative pain, and concluded that 10-20 mg Win 20,228 produced analgesia equivalent to 10 mg morphine. Cass, Frederik and Teodoro (1964) found that 40-mg doses of Win 20,228 approached but did not equal the analgesic effectiveness of 20 mg morphine. Paddock (personal communication, 1965) estimated the relative analgesic potency of Win 20,228 and morphine from collaborative studies in 300 patients. His results would suggest that as an analgesic 10 mg morphine is equivalent to 40 mg Win 20,228. The object of our investigation was to compare phenazocine and Win 20,228 directly in pain arising from abdominal surgery. Double-blind methods were used and assessments of pain by observer and patients were supplemented by objective measurements of changes in vital capacity.

20,228. The ampoules were numbered similarly by means of white ink on black adhesive tape; no other identifying markings were visible. At the time of injection pain was rated as mild (1), moderate (2) or severe (3) by either one of two of us and on this basis either 1 ml or 1.5 ml of analgesic solution was administered. At 30,60 and 120-minute intervals following injection, pain was rated again. Some of these ratings were made by the senior nurse on the ward. Patients were then asked whether their pain was less, the same, or worse than at the time of injection. Wherever possible, vital capacities were also recorded. Patients were not disturbed when they were sleeping. These measurements, all ratings, and any comments about the side effects, were noted on a separate card on each occasion. The cards were then filed and were not available for comparison when subsequent observations were made.

METHOD

RESULTS

The trial included patients admitted to the Mansfield Group of Hospitals over a five-month period. Women of child-bearing age were excluded, except those undergoing hysterectomy. Apart from avoiding the young, very elderly and the obviously unstable, and provided that the assessors and operators were available, then consecutive patients were included in the trial without other selection until a reasonable range of operative procedures had been covered. Patients were matched as closely as possible into pairs according to age, sex, body weight and operation. Trial numbers were allocated to such pairs of patients from a list previously prepared by a third person. The numbers in a pair had been chosen at random so that there was no way in which any number could be associated with either drug used in the trial. In most cases vital capacity was measured on a Vitalograph before patients were taken to theatre, after familiarization with the method. The same posture was used throughout. In nearly all cases the same surgeon operated on each patient of a pair. The patients were not given postoperative analgesic injections routinely; they were asked if they needed one for the pain. The injections were given intramuscularly from 1-ml ampoules in numbered boxes, corresponding to the patient's trial number. Each box contained four ampoules, either 4 x 2 mg phenazocine or 4 x 30 mg Win

One hundred and twenty-eight patients completed the trial and a total of 253 injections were given. Table I describes the patients, the type of operative procedures used, as well as the number and TABLE I

Description of two patient groups matched under double-blind conditions. Win 20,228

Number of men Number of women Men and women Age distribution (years) 11-20 21-30 31-40 41-50 51-60 • 61-70 71-80 Surgery Herniorrhaphy (8 bilateral) Hysterectomy Prostatectomy Appendicectomy Cholecystectomy Vagotomy and pyloroplasty Partial gastrectomy Partial nephrectomy Mastectomy Number of patients receiving: 1 injection 2 injections 3 injections or 4 injections

Phenazocine

45 20 65

43 20 63

1 5 10 25 12 9 3

1 6 9 23 13 10 1

18 15 4 1 9 16 0 1 1

18 15 4 1 7 15 1 1 1

23 21 18 3

28 16 14

5

PENTAZOCINE AND PHENAZOCINE

347

size of injections given. It is evident that the matching procedure adopted resulted in two very similar groups. Of the 65 patients in the Win 20,228 group, 21 had more than two injections; in the phenazocine group 19 out of 63 patients had more than two injections. Ninety-four out of the 151 Win 20,228 injections were of 1 ml, that is, 30 mg; the remaining 37 were 45 mg. Eightyone out of 122 phenazocine injections were of 2 mg; the other 41 were 3-mg injections. The average dosages for the first postoperative injection were 37.7 mg Win 20,228/70 kg body weight, and 2.6 mg phenazocine/70 kg body weight. Pain relief scores were computed by subtracting the pain intensity score at a given time from that recorded at time of injection (Houde, Wallenstein and Rogers, 1960). "No pain" was scored zero; for example, a patient who had moderate pain (2) at the time of injection and no pain (0) after 1 hour, would be credited with a pain relief score of (2—0) equal to 2.

Lasagna (1960) has shown that when a patient is sleeping in the postoperative period, this is not necessarily an indication of effective analgesia in the sense that there would be no report of pain if the patient were wakened. Since we did not consider it justifiable to waken our patients in order to rate pain, pain intensity was not recorded for patients asleep, and thus no pain relief score could be computed for the period concerned. Four patients in the Win 20,228 group and six in the phenazocine group, slept throughout the 2-hour postinjection periods and thus provided no pain relief score. Results from the observers' assessments are shown in tables II and HI. In table II responses to the two drugs are compared. The retabulation of the same results in table HI demonstrates differences in response depending on type of operative procedure. More than naif the patients had more than one injection. Section (i) of tables II and HI shows the distribution of 484 pain relief

TABLE II

Observers' assessments of pain intensity, expressed as pain relief scores (PJIS.) for the two analgesics (484 observations on 118 patients). (i)

Drug Win 20,228 Phenazocine

Hours after injection

(iii)

(ii)

Pain relief score distribution P R S. —— 0 1 2 3

N

Mean dosage (mg/ 70 kg)

No. of observations

Mean P.R.S.

31.8 50.5

169 83

1.12 1.23

4 24 28

2.2 3.3

148 84

1.14 1.21

3 17 33

0.5 1 2

22 11 12

38 44 47

29 20

1 2 3

46 42 47

0.5 1 2

23 12 8

43 34 36

16 28 27

0 1 4

43 41

23

Peak P.R.S. distribution P.R.S.

° - °* times patients sleeping

35

0

1 2

3

Mean peak P.R.S. 1.56

4

1.69

TABLE III

Pain relief scores after different types of surgery (retabulation of results shown in table II). (iii) (0 (ii) Pain relief score distribution P.R.S.

Peak P.R.S. distribution P.R.S.

0

1

2

3

No. of times patients sleeping

Upper and extraabdominal

0.5 1 2

13 3 8

36 28 27

21 25 28

0 2 2

33 44 40

1.30

1

12 32

4

1.80

Lower abdominal

0.5 1 2

32 20 12

45 50 56

18 32 19

1 1 5

48 41 48

1.06

6

29

5

1.48

Surgery

Hours after injection

Mean P.R.S.

0

1 2

3

Mean peak P.R.S.

29

BRITISH JOURNAL OF ANAESTHESIA

348

1-50 r-

LOWER ABDOMINAL PATIENTS

UPPER ABDOMINAL PATIENTS

30

60

120

0

30

60

120

MINUTES AFTER INJECTIONS Pentazocine 38 mg

Phenazocine 2-6 mg

FIG. 2 Change in mean pain relief scores with time; based on results shown in tables II and III.

score observations thus obtained at various times after all injections, and also shows the number of times that patients were asleep at time of assessment. Averages of these results are plotted against time in figure 2. In section (ii) of table II the overall average results are shown according to the dosage injected. Section (iii) shows the maximum relief recorded for each patient at any time during the trial. In the dosages used, the relief obtained from the two drugs was very similar. The mean pain relief score over all observations was 1.15 for Win 20,288 and 1.16 for phenazocine. The difference between the drugs at 2 hours after injection in patients who had

lower abdominal operations (fig. 2) would be expected to arise by chance between 5 and 10 times in any 100 similar similar trials. The mean peak pain relief score was 1.56 for Win 20,228 and 1.69 for phenazocinc. For all subsequent analyses patients who had lower abdominal operations, that is, hysterectomies, prostatectomies, herniorrhaphies and appendicectomies, have been considered separately from those who underwent upper abdominal or other procedures. Table HI shows that relief from pain in patients who had lower abdominal operations was consistently less than that obtained by other patients, as measured by

PENTAZOCINE AND PHENAZOCINE

349 TABLE IV

Distribution of patients' pain assessments after all injections (patients were not disturbed when sleeping) Upper abdominal

Surgery Drug

Win 20,228

Lower abdominal

Phenazocine

All opsrations

Phenazocine

Win 20,228

Phenazocine

Win 20,228

Hours after injection

0.5

1

2

0.5

1

2

0.5

1

2

0.5

1

2

0.5

1

2

0.5

1

2

Pain: Less Same Worse

29 6 1

24 1 0

18 6 0

24 6 0

23 3 0

24 6 0

41 5 0

56 1 0

45 5 2

41 10 0

44 3 0

37 4 1

70 11 1

80 2 0

63 11 2

65 16 0

67 6 0

61 10 1

pain relief score. The distributions over all times and both drugs were significantly different at the 2.5 per cent level, on analysis by the KolmogorovSmirnov Test of Goodness of Fit (Siegel, 1956). The peak pain relief score also reflects this difference. A peak score of 2 or 3 was achieved by 49 per cent of patients in the lower abdominal group, and by 74 per cent in the upper abdominal group. The difference is statistically significant (X3C = 5.98). Figure 2 illustrates that this difference obtained for both analgesics. The patients' own assessments of relief (table IV) show more frequent analgesia in the lower abdominal group, and this was so with both drugs. Overall, Win 20,228 gave relief 89 per cent of the time; for phenazocine the figure was 85 per cent. Following Masson (1962) the postoperative vital capacity measurements were expressed as a percentage of the pre-operative reading, and the effect of an injection was taken as the difference between percentages before and after the injection. In examining these results we sought answers to three questions: (1) To what extent was postoperative pain reflected in reductions in vital capacity? Table V compares the percentages achieved before injections were given for the different types of operative procedure. The average reduction of vital capacity for patients undergoing upper abdominal surgery was 70.1 per cent; for those who had lower abdominal surgery it was 38.6 per cent. The difference is statistically highly significant (P<0.001; SE of difference=4.67). (2) How did postinjection vital capacity measurements reflect pain relief after the different operative procedures and injections from different drugs? There were 70 patients for whom the vital capacity was recorded (a) before operation, (b)

TABLE V

Mean percentage of pre-operation vital capacities achieved, prior to first postoperative injection. Surgery

Number of cases

Mean percentage

Herniorrhaphy Prostatectomy Hysterectomy Vagotomy and pyloroplasty Cholecystectomy Partial gastrectomy

34 5 30 24 11 1

68.3 64.1 53.2 30.8 28.9 18.6

All lower abdominal All upper abdominal

69 36

61.4» 29.9*

* Standard error of difference=4.67.

immediately before the first postoperative injection and (c) at 1 hour after the injection. -Data from other patients were fragmentary and do not contribute to table VI. (Results from all those who had measurements (a) and (b) are included in table V.) All the mean increases in percentage vital capacity shown in table VI are statistically significant, at least at the 2.5 per cent level. This indicates that vital capacity measurements were capable of reflecting the analgesic effect of injections in all sub-groups of patients. The mean increase of 8.7 for patients with lower abdominal operations, considered as one group, is highly significant (P<0.001). However, neither the difference between upper and lower abdominal groups, nor the differences between the two analgesics are statistically significant. (3) "Does the efficacy of an analgesic drug depend upon how much pain the drug must relieve?" (Lasagna, 1962). Previous discussion of this question, by Lasagna (1962) and Oldham

350

BRITISH JOURNAL OF ANAESTHESIA TABLE

Increases in percentage

VI

vital capacity, 1 hour after first postoperative

Upper abdominal group Win 20,228 Number of patients Mean increase in percentage vital capacity Pooled variance estimates* Mean increases, adjusted for differences in pre-injection percentage vital capacity

Phenazocine

10 7.2

15.1

Both drugs

Win 20,228

PhenaTOcine

All operations Both drugs

Win 20,228

Phenazocine

19

27

24

51

37

33

10.9

9.2

8.1

8.7

8.1

10.0

121.43

157.68

7.9

injection.

Lower abdominal group

14.3

8.1

132.16

9.3

* Better variance estimates were obtained from analyses of covariance: for upper abdominal group s ' = 106.08; for lower abdominal group s'=94.14 (see text).

(1962a, b) has been in terms of pain scoring systems. Could our more objective vital capacity measurements shed further light on the problem? There was a significant correlation between the improvement in percentage vital capacity and percentage vital capacity prior to injection (fig. 3). For the lower abdominal group the regression coefficient (improvement regressed on pre-injection reading) was negative and highly significant (pooled b = - 0 . 2 9 5 5 , P<0.001). For these patients the bigger the decrease in vital capacity as a result of the operation, the better the response to the analgesic medication. A contrary tendency was apparent in the upper abdominal group: although the regression coefficient was significant at the 5 per cent level only, it was positive. This suggests that for these patients bigger improvements in vital capacity would occur when the effect of the operation was less severe. The adjusted mean improvements shown in table VI take account of the chance differences between the two drug groups in their pre-injection percentage vital capacities. They provide better estimates of the true effects of the two analgesics and can be regarded as mathematical estimates of the average results that would have been achieved for the two drugs had all patients recorded identical vital capacity percentages at the time of injection. Using Lasagna's (1962) terminology the adjusted means are estimates of

efficacy for both analgesics, given the same initial pain. Consideration of the unadjusted means would lead to the same conclusions as those reported above. For example, in the upper abdominal group mean increases for Win 20,228 and phenazocine before adjustment are 7.2 and 15.1 respectively. The difference is 7.9, with a standard error of 5.77. This indicates that the difference would be expected to arise by chance 18 or 19 times in any 100 similar trials. A significance test on the difference in adjusted means led to the same conclusion (P=0.20). No serious side effects were observed. A man aged 74 who had undergone prostatectomy felt cold, clammy and drowsy up to 1 hour following an injection of 45 mg Win 20,228. Three men felt drowsy after 2-mg injections of phenazocine. Two of them, aged 43 and 54 respectively, had undergone left inguinal herniorrhaphies;the third, aged 38, had a vagotomy and pyloroplasty. Another man, having had a similar operation, was slightly confused and hypotensive 2 hours after a 2-mg injection of phenazocine. Nausea and vomiting were not noted. One patient who had received phenazocine had a fatal pulmonary embolus after prostatectomy. There was one other patient with thrombophlebitis, and ten with chest infections, who also received phenazccine. In the Win 20,228 group, one patient had thrombophlebitis and six had chest infections.

PENTAZOCINE AND PHENAZOCINE

351

16 i -

14

12

a:

AVERAGE 10

o O

L±J — | LU

§2 6 4 CO <

<

LJJ

en O

2

10

20

30

40

50

60

PRE-INJECTION PAIN

70

80

90

100

*-

(100-%V.C. BEFORE INJECTION) FIG. 3 Relationship between pain relief following injections and level of pain before injection, as reflected in changes in percentages of pre-operative vital capacity. The two lines represent pooled slopes from analyses of covariancc of results from the lower and upper abdominal cases respectively. In lower abdominal cases the improvements in vital capacity increase as the level of pain, as measured by percentage vital capacity, increases. In the upper abdominal cases, improvements in vital capacity decrease as level of pain increases. DISCUSSION

Assessment of postoperative pain is notoriously difficult. Postoperative analgesic injections are sometimes given almost as a routine: Much can be done to reduce the number of these postoperative injections by sympathetic explanation and supervision (Egbert et al., 1964), and it has been suggested (Lancet, 1964) that this approach should be pursued wherever possible. Papper, Brodie and Rovenstine (1952) found that 27 per cent of 108 patients who had undergone intraabdominal or intrathoracic surgery required no analgesic in the postoperative period. Swerdlow,

Starmer and Daw (1964) reported the same percentage in 92 patients who had had a variety of abdominal operations. Out of 104 patients who had all undergone upper abdominal operations (Keats, 1956), 21 per cent required only one or no dose of analgesic. During the time of the trial reported here we found that a third of hernia patients and even two gall bladder patients did not require any postoperative analgesic injections at all. Before this trial began we had. already used phenazocine, particularly for daytime pain relief, and had been struck by the absence of vomiting.

352 We have found that some 8 per cent of 369 postoperative patients vomit with morphine and related alkaloids, depending on the patient's sex and age, the type of operation and, of course, the individual. Nausea and vomiting were not found with either phenazocine or Win 20,228. We have also given both phenazocine and Win 20,228 intravenously in doses similar to those used in the controlled study, and have noted considerable relief from pain, again without nausea or vomiting. Since chest complications are very common in our area it was hoped that pulmonary and thromboembolic complications would be reduced if the patients were both free from pain and able to cough well, and otherwise co-operate with their treatment. The relatively low incidence of such complications in this short series was encouraging. Conclusions from results must be restricted to the conditions of the study, that is, intramuscular injections of phenazocine and Win 20,228 to alleviate pain arising from abdominal surgery. Thirty-eight mg Win 20,228 was on average analgesically equivalent to 2.6 mg phenazocine. This does not constitute an estimate of potency in the sense that the word is used by pharmacologists. However, the initial pain intensity covered by the trial varied widely, as shown by the vital capacity results. Further, all criteria employed gave consistent comparisons of the drugs' analgesic effects. These considerations suggest that the results may have wider applicability than the specific conditions of this study. As pointed out by Cass (1964) extrapolations are useful in order to help plan suitable dose levels for further investigations. With this in mind the results from the present trial, considered together with the potency estimates of phenazocine relative to morphine given by Houde and colleagues (1964), may be taken to imply that for pain relief 10 mg morphine would be comparable with 33-44 mg Win 20,228, rather than 10-20 mg Win 20,228 as estimated by Keats and Telford (1964). Our estimate is in closer agreement with the work of Paddock (personal communication, 1965) who found that 10 mg morphine was equivalent to 40 mg Win 20,228 in patients with both postoperative and chronic pain. In their investigation of methods for assessing postoperative pain relief Parkhouse and Holmes

BRITISH JOURNAL OF ANAESTHESIA (1963) restricted themselves to upper abdominal cases. They found vital capacity an effective tool for discriminating morphine from saline. Masson had previously shown the usefulness of this measurement but he found that reductions in vital capacity on the first day after herniorrhaphy were small when compared with those found after upper abdominal surgery. The changes in vital capacity that he found in patients who had herniorrhaphies did not reflect a significant effect of intravenous analgesic injections. The results reported here, based on the first postoperative injection given intramuscularly to a larger number of patients, were able to show a significant improvement following injections in both upper and lower abdominal cases. Figure 3 shows the kind of changes in vital capacity improvements that appear to occur as the level of pain, as measured by percentage vital capacity, increases. It is based on slopes found from the analyses of covariance. As the level of pain increases in the lower abdominal group so the improvements likely to be made also increase. We could regard the lower part of this line as representing a range of pain in which the potential analgesic effect of the dosages used was greater than that actually required. As higher levels of pain are reached, typified by the upper abdominal cases, the ability of the injections to provide increasing relief becomes limited. Eventually the pain intensity is such that the variability in response to medication increases and the average level of response decreases. These vital capacity measurements have revealed a dependence of analgesic response to initial pain intensity in a quantitative fashion not possible with any scoring system. Both total and peak pain relief score results did show significantly more relief in the upper abdominal group, but it is not easy to assess how much of this was due to greater pain actually experienced by these patients and to what extent it was influenced by the fact that observers were well aware of the greater pain to be expected in upper abdominal surgery. If there was a subconscious bias present of the kind suggested, then this would not be expected to obtain in the patients' own assessments of relief. In this connection it is interesting to note that the patients' assessments reveal, if anything, a contrary tendency to that shown by the pain relief score data:

PENTAZOCINE AND PHENAZOCINE relief was obtained more frequently in the lower abdominal group. Whatever the nature of the correlation between pre-injection pain and relief, it remains to discriminate between this effect and that due to differences between analgesics under examination. Careful matching of drug groups, as effected in this study, will help. Vital capacity measurements are even more effective. Both these methods are particularly suited to the postoperative situation, where the between-patient type of design is often more suitable than the cross-over, for reasons discussed fully by Swerdlow, Murray and Daw (1963).

ACKNOWLEDGEMENTS

We are grateful to Mr. S. C. Anderson, Mr. R. T. Scars and Mr. A. McEwen Smith, some of whose patients were investigated. We are also indebted to Mr. P. J. O'Donnell of the Bayer Products Company for the supply of pentazocine, and much other assistance with the trial arrangements.

REFERENCES

Brit. med. J. (1964). Today's drugs. 2, 1119. Cass, L. J. (1964). Letter to the Editor. J. Amer. med. Ass., 189, 332. Frederik, W. S., and Teodoro, J. V. (1964). Pentazocine as an analgesic. J. Amer. med. Ass., 188, 112. Corbit, J. D. jr., and First, S. E. (1961). Clinical comparison of phenazocine and meperidine in obstetric analgesia. Obstet. and Gynec, 18, 488. Eckenhoff, J. E. (1959). Phenazocine, a new benzomorphan narcotic analgesic. Anesthesiology, 20, 355. Egbert, L. D., Battit, G. E., Welch, C. E., and Bartlett, M. K. (1964). Reduction of postoperative pain by encouragement and instruction of patients. New Engl. J. Med., 270, 825. Fraser, H. F., and Isbell, H. (1960). Human pharmacology and addiction liabilities of phenazocine and levophenacylmorphan. Bull. Narcot., 12 (2), 15. Rosenberg, D. E., (1964). Studies of the human addiction liability of 2'-hydroxy-5,9-dimethyl-2-(3, 3-dimethylallyl)-6,7-benzomorphan (WIN. 20,228): a weak narcotic antagonist. J. Pharm. Pharmacol., 143, 149. Harris, L. S., and Pierson, A. K. (1964). Some narcotic antagonists in the benzomorphan series. J. Pharm. Pharmacol., 143, 141. Houde, R. W., Wallenstein, S. L., Bellville, J. W., Rogers, A., and Escarraga, L. A., (1964). The relative analgesic and respiratory effects of phenazocine and morphine. J. Pharm. Pharmacol., 144, 337. Rogers, A. (1960). Clinical pharmacology of analgesics. 1: A method of assaying analgesic effect, Clin. Pharmacol. Ther., 1, 163.

353 Jolly, C. (1962). Phenazocine with nitrous oxide anaesthesia. Brit. J. Anaesth., 34, 571. Keats, A. S. (1956). Postoperative pain; research and treatment. J. chron. Dts., 4, 72. Telford, J. (1964). Studies of analgesic drugs. VIII: A narcotic antagonist analgesic without psychotomimetic effects. J. Pharm. Pharmacol., 143, 157. Leading article (1964). Relief of postoperative pain. Lancet, 2, 188. Lasagna, L. (1960). The Hiniral measurement of pain. Arm. N.Y. Acad. Sci., 86, 28. (1962). The psychophysics of clinical pain. Lancet, 2, 572. (1964). The clinical evaluation of morphine and its substitutes as analgesics. Pharmacol. Rev., 16, 47. Masson, A. H. B. (1962). Clinical assessment of analgesic drugs: spirometry trial. Anesth. Analg. Curr. Res., 41, 615. Oldham, P. D. (1962a). The psychophysics of clinical pain. Lancet, 2, 111. (1962b). A note on the analysis of repeated measurements of the same subjects. J. chron. Dis., 15, 969. Papper, E. M., Brodie, B. B., and Rovenstine, E. A. (1952). Postoperative pain; its use in the comparative evaluation of analgesics. Surgery, 32, 107. Parkhouse, J., and Holmes, C M. (1963). Assessing postoperative pain relief. Proc. toy. Soc. Med., 56, 579. Sadove, M. S., Schiffrin, M. L., and Heller, R. jr. (1959). A clinical comparison of two new narcotic analgesics. Curr. ther. Res., 1, 109. Siegel, S. (1956). Non-Parametric Statistics for the Behavioral Sciences. New York: McGraw-Hill. Swerdlow, M , Murray, A., and Daw, R. H. (1963). A study of postoperative pain. Acta anaesth. scand., 7, 1. Starmer, G., and Daw, R. H. (1964). A comparison of morphine and phenazocine in postoperative pain. Brit. J. Anaesth., 36, 782. PENTAZOCINE ET PHENAZOCINE: COMPARAISON EN DOUBLE INSU DE DEUX DERIVES DE LA BENZOMORPHINE SUR LES DOULEURS POST-OPERATOIRES SOMMAIRE

Les effets analgesiques des injections intra-musculaires de 30 et 45 mg de pentazocine (Win 20.228) ont €tt compares a ceux de 2 et 3 mg de phenazocine (Narphene) chez 128 malades souffrant apres une intervention abdominale. On a donni les drogues au hasard a des malades bien assortis par paires. La douleur a 6ti evaluee dans les conditions de double insu, on a not£ l'amelioration subjective des malades et mesuri la capacity vitale. Les deux drogues ont eti actives pour soulager les douleurs post-opiratoires et n'ont pas provoqui de nausees ni de vomissements. En moyenne, 38 mg de Win 20.228 dtaient analgesiquement equivalents 4 2,6 mg de phinazocine. Les modifications de la capacity vitale ont donai une bonne indication de la suppression des douleurs apres les operations de l'abdomen tant superieur qu'inferieur. On a trouvi que ces modifications 6taient en correlation significative avec la capacity vitale avant l'injection.

354

BRITISH JOURNAL OF ANAESTHESIA

PENTAZOCINE UND PHENAZOCINE: EINE VERGLEICHENDE UNTERSUCHUNG UBER ZWEI BENZOMORPHAN-DERIVATE FUR DIE POSTOPERATIVE SCHMERZBEKAMPFUNG IM DOPPELBLINDVERSUCH ZUSAMMENFASSUNG

Bei 128 Patienten mit Schmerzen nach bauchchirurgischen Eingriffen wurdc die analgetische Wirkung von 30 und 45 mg Pentazocine (Win 20,228) im Verjjteich zu 2 und 3 mg Phenazocine (Narphen) bei lntramuskularer Verabfolgung verglichen. Den gut kombinierten Patientenpaaren wurden die Medikamente blindlings zugeteilt. Die Schmerzempfindung wurde

unter den Bedingungen des Doppelblindversuches beurteilt, die Angaben der Patienten uber die Schmerzerleichterung aufgezeichnet und Bestimmungen der Vitalkapazitat vorgenommen. Fflr die Linderung der postoperativen Schmerzen erwiesen sich beide Medikamente als wirksam und sie verursachten keinen Brechreiz oder Erbrechen. Im Durchschnitt entsprachen 38 mg Win 20,228 in analgetischer Hinsicht 2,6 mg Phenazocine. Verandenmgen der Vitalkapazitat waren ein guter Indikator fur die Linderung des postoperativen Schmerzes nach Eingriffen im Oberund Unterbauch. Es wurde festgestellt, da8 diese Veranderungen in signiflkanter Beziehung zu der Vitalkapazitat vor der Injcktion standen.

THE FOURTH CONGRESS OF THE WORLD FEDERATION OF SOCIETIES OF ANAESTHESIOLOGISTS The fourth Congress of the World Federation of Societies of Anaesthesiologists will be held in London in the second week of September 1968. The host society is the Association of Anaesthetists of Great Britain and Ireland, and the following are the members of the Organizing Committee: Dr. G. Ellis (Chairman). Dr. P. J. HelliwelL Dr. D. D. C. Howat (Secretary). Dr. Q B. Lewis. Dr. C. F. Scurr. Dr. F. G. Wood-Smith (Treasurer). Dr. R. B. Wright.