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COMPARISON OF MEPTAZINOL AND PETHIDINE GIVEN I.V. ON DEMAND IN THE MANAGEMENT OF POSTOPERATIVE PAIN
Br. J. Anaesth. (1981), 53, 927
COMPARISON OF MEPTAZINOL AND PETHIDINE GIVEN I.V. ON DEMAND IN THE MANAGEMENT OF POSTOPERATIVE PAIN P. J. SLATTERY, M. HARMER, M. ROSEN AND M. D. VICKERS SUMMARY
Meptazinol and pethidine were compared under double-blind conditions in 20 patients, using an ondemand analgesic system to provide pain relief after upper abdominal surgery. The degree of analgesia, subjectively assessed, was good with both meptazinol and pethidine; although meptazinol produced significantly more nausea than did pethidine (P< 0.01), there was no statistically significant difference in the frequency of other side-effects. Over 24 h average consumption of meptazinol was 2.4 times that of pethidine, suggesting that, when given by i.v. injection, meptazinol is less potent than pethidine.
P. J. SLATTERY, MB., B.S., F.F.A.R.A.C.S.; M. HARMER, M.B., B.S., F.F.A.R.C.S.; M. ROSEN, M.B., B.CH., F.F.A.R.C.S.; M. D. VICKERS,
M.B., B.s., F.F.A.R.C.S.; Department of Anaesthetics, Welsh National School of Medicine, Heath Park, Cardiff CF4 4XN. 0007-0912 81 090927-05 801.00
METHODS
Patients in the trial presented for elective upper abdominal surgery, had no complications and were within the age range 16-70 yr. Females who were pregnant were excluded. The trial was conducted double-blind, patients being allocated randomly to groups of 10, to receive pethidine or meptazinol for 24 h after operation. The analgesic was administered i.v. by a patient-controlled syringe pump (Evans et al., 1976), available as the Cardiff Palliator (Pye Dynamic Ltd). Each patient was visited on the evening before surgery to obtain informed consent, and was instructed in the use of the apparatus and introduced to the concept of the linear analogue (Huskisson, 1974; Revill et al., 1976). The patients were premedicated with diazepam (approximately 0.15 mgkg~') administered orally 1-2 h before operation. Anaesthesia was induced with i.v. thiopentone, the trachea intubated after the administration of suxamethonium or a nondepolarizing muscle relaxant and the lungs were ventilated with halothane in nitrous oxide in oxygen. Up to 0.2 mg of fentanyl was given i.v. At the end of the operation residual neuromuscular blockade was antagonized using atropine and neostigmine. On arrival in the recovery ward the Cardiff Palliator was connected to the patient's i.v. infusion using a valved Y connector (Rosen and Williams, 1979). The Palliator was set to deliver an incremental dose of 1 ml of analgesic solution with a minimum interval of lOmin between doses. The analgesic concentrations were meptazinol 50mgml~' and pethidine 30mgml"'—concentrations found to be appropriate in preliminary © Macmillan Publishers Ltd 1981
Downloaded from http://bja.oxfordjournals.org/ by guest on March 26, 2016
Meptazinol (m-(3-ethyl-l -methyl hexahydro-1H-azepin-3-yl) phenol hydrochloride), an opiate antagonist, has been shown in animal studies to have potent analgesic effects and low dependence liability (Goode and White, 1971). In man, i.v. administration of meptazinol lmgkg"' to six volunteers produced no significant changes in arterial pressure and heart rate, and gave generally satisfactory relief of pain in 39 patients suffering from renal colic (Oosterlinck and deSy, 1975). Meptazinol administered by i.m. injection to patients recovering from lower abdominal and orthopaedic surgery has been found to give good relief of pain after operation (Paymaster, 1976, 1977; Hedges, Turner and Wadsworth, 1980). In an open study in our department, meptazinol given by i.v. injection produced good relief of severe pain after operation without inducing sedation in six of eight patients. Meptazinol lOOmg i.m. causes little respiratory depression when given to conscious pain-free volunteers (Jordan et al., 1979). Pethidine is a suitable standard for comparison: it is widely used as a postoperative analgesic, and has been successfully used in an i.v. on-demand infusion system (Chakravarty et al., 1979). Several analgesic drugs were compared in a double-blind trial utilizing on-demand i.v. infusion to provide analgesia for patients recovering from upper abdominal surgery. We report here the results obtained for pethidine and meptazinol.
928
BRITISH JOURNAL OF ANAESTHESIA RESULTS
The group of patients reported here consisted of 15 females and five males. By chance the meptazinol group were heavier than the pethidine group, so all drug consumptions are compared in weight-related terms. Details of each patient are presented in table I. The number of demands made in 24 h and the quantity of drug used by each group is shown in table II. 2-4 h assessment. Observer assessment consisted of noting the presence or absence of sweating, pallor, retching or wincing. The frequency of these occurrences in the two groups was compared using the Fisher Exact Probability test and found not to be significantly different (table III). Conscious state was assessed on a 1—4 scale and the patients were questioned regarding pain, dizziness, nausea and mood change, using a 1-5 scale for degree. These scores were compared using the Mann-Witney U test. Analysis of all the 2-4 h assessment scores showed no significant differences between those receiving pethidine and those receiving meptazinol. 24-h assessment. At the end of 24 h the patients were requested to mark six 10-cm linear analogues. The linear analogue for each sensation ranged from none at one end to the greatest imaginable degree at the other. The subject of each analogue and the results, given on a 0-100 scale, are shown in table IV. Analysis of linear analogue scores by the Mann-Whitney U test showed that patients
TABLE I. Patient details. * This patient was removed from the trial after 19 h because of unsatisfactory analgesia. The dose shown is that consumed in 19 h. Data from this patient are not included in further statistical analyses Meptazinol
Pethidine
No.
Age (yr)
1 2 3 4 5 6 7 8 9 10 Mean
57 53 31 51 52 57 47 59 58 54 52
Sex F F F F F F F M F F
Wt (kg) 68 47 80 63 51 70 57 56 56 73 62
Operation
Total dose (mg)
Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Vagotomy Cholecystectomy Cholecystectomy
240 420 540 390 330 930 840 780 690 960
No.
Age (yr)
1* 2 3 4 5 6 7 8 9 10 Mean
61 34 48 45 36 41 46 47 49 60 47
Sex M F F F F F M F M M
Wt (kg) 71 69 75 67 75 83 89 70 85 82 77
Operation
Total dose (mg)
Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Vagotomy Cholecystectomy
3450 2900 2050 750 1650 1050 1050 2800 2900 1350
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open studies. On wakening, the patient was given the demand control and reminded of how to use it; if necessary the patient was helped with the initial doses. Patients were kept in the recovery ward until able to use the Palliator without assistance, and then returned to the surgical ward free to take the analgesic as required. Arterial pressure, heart rate and respiratory frequency were recorded as usual by ward staff. Metoclopramide lOmg to be given i.m. was prescribed for any patient who complained of nausea or vomited, and an alternative i.m. analgesic regime was provided in the event of rejection of the i.v. on-demand system. Between 2 and 4h after operation the patients were visited on the ward by a research nurse, assessed with regard to physical and conscious state, and questioned as to the degree of pain, dizziness, nausea and change of mood. At 24 h after operation, patients were again visited and asked to mark linear analogues representing overall pain, dizziness, drowsiness, nausea and mood. Patients were also questioned directly concerning pain and the occurrence of unpleasant dreams. The Palliator was then removed and an analgesic prescribed to be given i.m. when required. Examination of the distribution of linear analogue scores for dizziness, nausea, elation and depression showed positive skew, so these scores for the two drugs were compared using the Mann-Whitney U test, which was also used to analyse non-continuous data. Qualitative data were analysed by the Fisher Exact Probability test.
I.V. MEPTAZINOL FOR POSTOPERATIVE ANALGESIA TABLE II. Analgesic doses
No. of demands in24h Pethidine (n = 10) Mean Range SD SEM Meptazinol (*»9) Mean Range SD SEM
Dose (mg)
Dose (mgkg"1 per 24 h)
19 8-32 10.0 3.2
570 240-960
9.94 3.52-14.83 4.04 1.28
37 15-58 17.2 5.7
1850 750-2900
24.16 11.19-42.03 12.20 4.07
Meptazinol (n = 9)
Significance* P P P P
= = = =
0.25 0.58 0.74 0.21
TABLE IV. Linear analogue results. *0 •= none; 100 = extreme. ^Assessed by Mann-Whitney U test Analogue score*
(mean ± SEM) Pethidine
Meptazinol
Significancet
42.7 ±8.7 55.3±13.5 3.5 ±1.9 5.5±5.0 25.5±9.8 9.3 ±5.0
43.1 ±9.2 52.2±12.6 24.1±11.5 56.8± 11.8 27.2±13.1 24.2 ±11.2
P>0.05 P>0.05 P>0.05 P<0.0l P>0.05 P>0.05
receiving meptazinol experienced significantly more nausea than those receiving pethidine (P<0.01); dizziness scores were also greater, but not significantly so. All patients were questioned as to the overall degree of pain felt, using a five-point scale ranging from no pain to very severe pain. A similar scale was used to assess unpleasant dreaming. The dream and pain ratings were compared and there was no significant difference between the two
Interval after operation (h) 0-3 3-6 6-12 12-24 10-24
Analgesic consumption (mgkg-'h' 1 ) (mean ± SEM) Pethidine
Meptazinol
Relative consumption (meptazinol/ pethidine)
0.68 ±0.06 O.35±O.O5 0.34±0.05 0.40±0.06 0.41 ±0.05
1.87 ±0.28 1.64±2.28 0.92 + 0.17 0.66 + 0.14 1.01+0.17
2.75 times 4.5 times 2.72 times 1.66 times 2.4 times
DISCUSSION
Patients in this study had the same types of operation and anaesthetic technique as those studied by Chakravarty and others (1979). Both groups used the Cardiff Palliator to provide pain relief after operation, and mean pethidine consumption was similar—9.05 mgkg" 1 per 24h in the earlier study and 9.94 mg kg" ' per 24 h in the group reported here. Patients using trjese infusion systems do not consume excessive amounts of drug—a mean pethidine consumption of 9.94mgkg~' per 24 h is equivalent to 116mg every 4 h in a 70-kg patient. Mean analogue pain scores after meptazinol and pethidine were almost identical at 43.1 and 42.7 respectively. Given that the overall degree of pain relief was the same, we propose that an indication of relative potency of the drugs can be derived from the amounts of analgesic consumed. The meptazinol: pethidine consumption ratios ranged from 4.5:1 to 1.6:1 at varying times after surgery, with a mean over 24 h of 2.4:1. This result seems to be at variance with the conclusion of Paymaster (1977), who suggested that the drugs Were equipotent; however our study and his are not strictly comparable as two different techniques of drug administration were used, and the patients
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Pethidine (n •= 10)
Sweating Pallor Retching Wincing
Pain Drowsiness Dizziness Nausea Elation Depression
groups in either of these ratings. Antiemetics were administered to six patients in the pethidine group, and to eight patients in the meptazinol group. From the collected data it was possible to calculate the mean analgesic consumption for selected intervals within the 24-h period. This information is presented in table V.
TABLE V. Time-related analgesic consumption
TABLE III. 2-4h postoperative observer assessment (number in eachgroup with positive observation). *Assessed by Fisher's Exact Probability test Observations
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BRITISH JOURNAL OF ANAESTHESIA
930
ACKNOWLEDGEMENTS
We would like to thank Mrs M. Davies, Miss P. James and Mrs J. Webster for their valuable assistance.
REFERENCES
Chakravarty, K., Tucker, W., Rosen, M., and Vickers, M. D. (1979). Comparison of buprenorphine and pethidine given intravenously on demand to relieve postoperative pain. Br. Med. J., 2, 895. Evans, J. M., Rosen, M., MacCarthy, J., and Hogg, M. I. J., (1976). Apparatus for patient controlled administration of intravenous narcotics during labour. Lancet, 1, 17. Gibbs, J. M., and Johnson, H. D. (1980). A trial of meptazinol for the relief of pain after abdominal surgery. Anaesth. Intern. Care, 8,441. Goode, P. G., and White, A. C.(1971). Some properties of WY 22811, a new analgesic compound. Br.J. Pharm., 43, 462P. Hedges, A., Turner, P., and Wadsworth, J. (1980). A doubleblind comparison of meptazinol with pethidine in postoperative pain. Br. J. Anaesth., 52, 295. Huskisson, E. C. (1974). Measurement of pain. Lancet, 1, 17. Jordan, C , Lehane, J. R., Robson, P. J., and Jones, J. G., (1979). A comparison of the respiratory effects of meptazinol, pentazocine and morphine. Br. J. Anaesth., 51, 497. Oosterlinck, W., and deSy, W. (1975). Preliminary clinical experience with meptazinol, a new analgesic. Curr. Med. Res. Opin., 3, 187. Parkhouse, J., Lambuchts, W., and Simpson, B. R. J. (1961). The incidence of postoperative pain. Br.J. A natsth., 33,345. Paymaster, N. J. (1976). Clinical evaluation of meptazinol, a new analgesic, in postoperative pain. Br.J. Anaesth., 48,599. (1977). Analgesia after operation—a controlled comparison of meptazinol, pentazocine and pethidine. Br. J. Anaesth., 49, 1139. Revill, S. I., Robinson, J. Q., Rosen, M., and Hogg, M. I. J. (1976). The reliability of a linear analogue for evaluating pain. Anaesthesia, 31, 1191. Rosen, M., and Williams, B. (1979). The Valved-Y-Cardiff connector (V. Y. C. Con). Anaesthesia, 34, 882. Swerdlow, M., Starmer, G., and Daw, R. H., (1964). A comparison of morphine and pentazocine in postoperative pain. Br. J. Anaesth., 36, 782.
COMPARAISON DU MEPTAZINOL ET DE LA PETHIDINE ADMINISTRES PAR VOIE INTRAVEINEUSE SUR DEMANDE POUR LE SOULAGEMENT DES DOULEURS POSTOPERATOIRES RESUME
On a compare le meptazinol et la pethidine, au cours d'une etude a double inconnue effecruce sur 20 patients, en utilisant un systeme analgesique sur demande permettant de soulager la douleur apres toute intervention chirurgicale a la partie superieure de Pabdomen. Le degrc d'analgesie, estime d'une maniere subjective, a etc satisfaisant aussi bien avec le meptazinol qu'avec la pethidine; bien que le meptazinol ait produit davantage de nausees que la pethidine (P<0,01), il n'y a eu aucune difference significative du point de vue statistique dans la frequence des autres effets secondaires. Sur une periode de 24 h la consommation moyenne de meptazinol a ete de 2,4 fois plus elevee que celle de pethidine, ce qui laisse penser que lorsqu'il est administrc en injection, le meptazinol est moins puissant que la pethidine.
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were dissimilar. Paymaster administered meptazinol i.m. and investigated a group of patients who had undergone lower abdominal and orthopaedic surgery. Upper abdominal wounds cause severe pain and high analgesic requirement (Parkhouse, Lambuchts and Simpson, 1961; Swerdlow, Starmer and Daw, 1964). One patient using meptazinol was removed from the trial because of inadequate analgesia; before this he recorded the highest drug consumption rate in the group, but still gave high pain, nausea and dizziness scores, despite the administration of an anti-emetic. Examination of this patient's demand record showed that the rate of analgesic consumption had been limited by the pre-set minimum interval between doses. It is probable that if he had been permitted to consume more drug, the degree of pain relief would have been greater. Patients receiving meptazinol had significantly higher scores for nausea than those receiving pethidine. This is consistent with previously published observations (Oosterlinck and deSy, 1975; Gibbs and Johnson, 1980). No evidence of dysphoria was seen with either drug, and no patient reported unpleasant dreams. Meptazinol behaves as a potent analgesic, but larger amounts were consumed than would be expected from previously suggested potency ratios, the most likely explanation being that meptazinol is less potent than pethidine. As meptazinol produced more nausea and, perhaps, also more dizziness than pethidine, it does not seem an improvement on pethidine when administered by intermittent i.v. injection. Meptazinol however, was shown by Jordan and others (1979) to produce less respiratory depression than morphine when given to conscious volunteers by i.m. injection in doses considered to be equianalgesic: meptazinol lOOmg, and morphine lOmg (which is roughly comparable to pethidine 100 mg). If this advantageous comparison with traditional analgesics on i.m. injection holds true when meptazinol is given i.v. in the higher doses (2.4 x) found to be equianalgesic with pethidine in this study, meptazinol may still prove a safe and useful drug in the control of severe pain after surgery.
931 VERGLEICH ZWISCHEN WUNSCHGEMASS ZUR POSTOPERATIVEN SCHMERZLINDERUNG INTRAVENOS GEGEBENEN DOSEN VON MEPTAZINOL UND PETHIDIN
COMPARACION DEL MEPTAZINOL Y DE LA PETIDINA ADMINISTRADAS INTRAVENOSAMENTE SEGUN LA DEMANDA PARA LA GERENCIA DEL DOLOR POSOPERATIVO
ZUSAMMENFASSUNG
Metazinol und Pethidin wurden unter DoppelbhndBedingungen bei 20 Patienten verglichen, bei Verwendung eines Schmerzlinderungssystems auf Wunsch nach Operationen im oberen Unterleib. Das subjektiv bewcrtete Ausmass dcr Schmerzlinderung war bei beiden Drogen zufriedenstellend: obwohl Meptazinol wesentlich mehr Obelkeit bewirkte als Pethidin (P<0,01), gab es keine statistisch wesentlichen Unterschiede in der Haufigkeit anderer Nebenerscheinungen. Ober 24 Stunden betrug de Durchschnittsverbrauch von Meptazinol um 2,4-mal mehr als von Pethidin, was zeigt, das intravends gegebenes Meptazinol weniger stark wirkt als Pethidin.
Se compararon el meptazinol y la petidina en 20 pacientes y bajo condiciones de doble anonimato mediante un sistema anaigesico de administracion segiin la demanda, para aliviar el dolor despues de operacion quiriirjica del abdomen supenor. El grado de anestesia, evaluado subjetivamente, fue el adecuado tanto para el meptazinol como para la petidina; aunque aquel produjo nauseas de una forma mas signincativa que lo hizo la petidina (P< 0,01) no hubo una diferencia estadistica signincativa en la frccuencia de otros efectos secundarios durante 24 horas. El consumo medio de meptazinol fue 2,4 veces mayor que el de petidina, lo que sugiere cuando la administracion es intravenosa aquel es menos potente que csta. Downloaded from http://bja.oxfordjournals.org/ by guest on March 26, 2016
COMPARISON OF MEPTAZINOL AND PETHIDINE GIVEN I.V. ON DEMAND IN THE MANAGEMENT OF POSTOPERATIVE PAIN P. J. SLATTERY, M. HARMER, M. ROSEN AND M. D. VICKERS SUMMARY
Meptazinol and pethidine were compared under double-blind conditions in 20 patients, using an ondemand analgesic system to provide pain relief after upper abdominal surgery. The degree of analgesia, subjectively assessed, was good with both meptazinol and pethidine; although meptazinol produced significantly more nausea than did pethidine (P< 0.01), there was no statistically significant difference in the frequency of other side-effects. Over 24 h average consumption of meptazinol was 2.4 times that of pethidine, suggesting that, when given by i.v. injection, meptazinol is less potent than pethidine.
P. J. SLATTERY, MB., B.S., F.F.A.R.A.C.S.; M. HARMER, M.B., B.S., F.F.A.R.C.S.; M. ROSEN, M.B., B.CH., F.F.A.R.C.S.; M. D. VICKERS,
M.B., B.s., F.F.A.R.C.S.; Department of Anaesthetics, Welsh National School of Medicine, Heath Park, Cardiff CF4 4XN. 0007-0912 81 090927-05 801.00
METHODS
Patients in the trial presented for elective upper abdominal surgery, had no complications and were within the age range 16-70 yr. Females who were pregnant were excluded. The trial was conducted double-blind, patients being allocated randomly to groups of 10, to receive pethidine or meptazinol for 24 h after operation. The analgesic was administered i.v. by a patient-controlled syringe pump (Evans et al., 1976), available as the Cardiff Palliator (Pye Dynamic Ltd). Each patient was visited on the evening before surgery to obtain informed consent, and was instructed in the use of the apparatus and introduced to the concept of the linear analogue (Huskisson, 1974; Revill et al., 1976). The patients were premedicated with diazepam (approximately 0.15 mgkg~') administered orally 1-2 h before operation. Anaesthesia was induced with i.v. thiopentone, the trachea intubated after the administration of suxamethonium or a nondepolarizing muscle relaxant and the lungs were ventilated with halothane in nitrous oxide in oxygen. Up to 0.2 mg of fentanyl was given i.v. At the end of the operation residual neuromuscular blockade was antagonized using atropine and neostigmine. On arrival in the recovery ward the Cardiff Palliator was connected to the patient's i.v. infusion using a valved Y connector (Rosen and Williams, 1979). The Palliator was set to deliver an incremental dose of 1 ml of analgesic solution with a minimum interval of lOmin between doses. The analgesic concentrations were meptazinol 50mgml~' and pethidine 30mgml"'—concentrations found to be appropriate in preliminary © Macmillan Publishers Ltd 1981
Downloaded from http://bja.oxfordjournals.org/ by guest on March 26, 2016
Meptazinol (m-(3-ethyl-l -methyl hexahydro-1H-azepin-3-yl) phenol hydrochloride), an opiate antagonist, has been shown in animal studies to have potent analgesic effects and low dependence liability (Goode and White, 1971). In man, i.v. administration of meptazinol lmgkg"' to six volunteers produced no significant changes in arterial pressure and heart rate, and gave generally satisfactory relief of pain in 39 patients suffering from renal colic (Oosterlinck and deSy, 1975). Meptazinol administered by i.m. injection to patients recovering from lower abdominal and orthopaedic surgery has been found to give good relief of pain after operation (Paymaster, 1976, 1977; Hedges, Turner and Wadsworth, 1980). In an open study in our department, meptazinol given by i.v. injection produced good relief of severe pain after operation without inducing sedation in six of eight patients. Meptazinol lOOmg i.m. causes little respiratory depression when given to conscious pain-free volunteers (Jordan et al., 1979). Pethidine is a suitable standard for comparison: it is widely used as a postoperative analgesic, and has been successfully used in an i.v. on-demand infusion system (Chakravarty et al., 1979). Several analgesic drugs were compared in a double-blind trial utilizing on-demand i.v. infusion to provide analgesia for patients recovering from upper abdominal surgery. We report here the results obtained for pethidine and meptazinol.
928
BRITISH JOURNAL OF ANAESTHESIA RESULTS
The group of patients reported here consisted of 15 females and five males. By chance the meptazinol group were heavier than the pethidine group, so all drug consumptions are compared in weight-related terms. Details of each patient are presented in table I. The number of demands made in 24 h and the quantity of drug used by each group is shown in table II. 2-4 h assessment. Observer assessment consisted of noting the presence or absence of sweating, pallor, retching or wincing. The frequency of these occurrences in the two groups was compared using the Fisher Exact Probability test and found not to be significantly different (table III). Conscious state was assessed on a 1—4 scale and the patients were questioned regarding pain, dizziness, nausea and mood change, using a 1-5 scale for degree. These scores were compared using the Mann-Witney U test. Analysis of all the 2-4 h assessment scores showed no significant differences between those receiving pethidine and those receiving meptazinol. 24-h assessment. At the end of 24 h the patients were requested to mark six 10-cm linear analogues. The linear analogue for each sensation ranged from none at one end to the greatest imaginable degree at the other. The subject of each analogue and the results, given on a 0-100 scale, are shown in table IV. Analysis of linear analogue scores by the Mann-Whitney U test showed that patients
TABLE I. Patient details. * This patient was removed from the trial after 19 h because of unsatisfactory analgesia. The dose shown is that consumed in 19 h. Data from this patient are not included in further statistical analyses Meptazinol
Pethidine
No.
Age (yr)
1 2 3 4 5 6 7 8 9 10 Mean
57 53 31 51 52 57 47 59 58 54 52
Sex F F F F F F F M F F
Wt (kg) 68 47 80 63 51 70 57 56 56 73 62
Operation
Total dose (mg)
Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Vagotomy Cholecystectomy Cholecystectomy
240 420 540 390 330 930 840 780 690 960
No.
Age (yr)
1* 2 3 4 5 6 7 8 9 10 Mean
61 34 48 45 36 41 46 47 49 60 47
Sex M F F F F F M F M M
Wt (kg) 71 69 75 67 75 83 89 70 85 82 77
Operation
Total dose (mg)
Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Cholecystectomy Vagotomy Cholecystectomy
3450 2900 2050 750 1650 1050 1050 2800 2900 1350
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open studies. On wakening, the patient was given the demand control and reminded of how to use it; if necessary the patient was helped with the initial doses. Patients were kept in the recovery ward until able to use the Palliator without assistance, and then returned to the surgical ward free to take the analgesic as required. Arterial pressure, heart rate and respiratory frequency were recorded as usual by ward staff. Metoclopramide lOmg to be given i.m. was prescribed for any patient who complained of nausea or vomited, and an alternative i.m. analgesic regime was provided in the event of rejection of the i.v. on-demand system. Between 2 and 4h after operation the patients were visited on the ward by a research nurse, assessed with regard to physical and conscious state, and questioned as to the degree of pain, dizziness, nausea and change of mood. At 24 h after operation, patients were again visited and asked to mark linear analogues representing overall pain, dizziness, drowsiness, nausea and mood. Patients were also questioned directly concerning pain and the occurrence of unpleasant dreams. The Palliator was then removed and an analgesic prescribed to be given i.m. when required. Examination of the distribution of linear analogue scores for dizziness, nausea, elation and depression showed positive skew, so these scores for the two drugs were compared using the Mann-Whitney U test, which was also used to analyse non-continuous data. Qualitative data were analysed by the Fisher Exact Probability test.
I.V. MEPTAZINOL FOR POSTOPERATIVE ANALGESIA TABLE II. Analgesic doses
No. of demands in24h Pethidine (n = 10) Mean Range SD SEM Meptazinol (*»9) Mean Range SD SEM
Dose (mg)
Dose (mgkg"1 per 24 h)
19 8-32 10.0 3.2
570 240-960
9.94 3.52-14.83 4.04 1.28
37 15-58 17.2 5.7
1850 750-2900
24.16 11.19-42.03 12.20 4.07
Meptazinol (n = 9)
Significance* P P P P
= = = =
0.25 0.58 0.74 0.21
TABLE IV. Linear analogue results. *0 •= none; 100 = extreme. ^Assessed by Mann-Whitney U test Analogue score*
(mean ± SEM) Pethidine
Meptazinol
Significancet
42.7 ±8.7 55.3±13.5 3.5 ±1.9 5.5±5.0 25.5±9.8 9.3 ±5.0
43.1 ±9.2 52.2±12.6 24.1±11.5 56.8± 11.8 27.2±13.1 24.2 ±11.2
P>0.05 P>0.05 P>0.05 P<0.0l P>0.05 P>0.05
receiving meptazinol experienced significantly more nausea than those receiving pethidine (P<0.01); dizziness scores were also greater, but not significantly so. All patients were questioned as to the overall degree of pain felt, using a five-point scale ranging from no pain to very severe pain. A similar scale was used to assess unpleasant dreaming. The dream and pain ratings were compared and there was no significant difference between the two
Interval after operation (h) 0-3 3-6 6-12 12-24 10-24
Analgesic consumption (mgkg-'h' 1 ) (mean ± SEM) Pethidine
Meptazinol
Relative consumption (meptazinol/ pethidine)
0.68 ±0.06 O.35±O.O5 0.34±0.05 0.40±0.06 0.41 ±0.05
1.87 ±0.28 1.64±2.28 0.92 + 0.17 0.66 + 0.14 1.01+0.17
2.75 times 4.5 times 2.72 times 1.66 times 2.4 times
DISCUSSION
Patients in this study had the same types of operation and anaesthetic technique as those studied by Chakravarty and others (1979). Both groups used the Cardiff Palliator to provide pain relief after operation, and mean pethidine consumption was similar—9.05 mgkg" 1 per 24h in the earlier study and 9.94 mg kg" ' per 24 h in the group reported here. Patients using trjese infusion systems do not consume excessive amounts of drug—a mean pethidine consumption of 9.94mgkg~' per 24 h is equivalent to 116mg every 4 h in a 70-kg patient. Mean analogue pain scores after meptazinol and pethidine were almost identical at 43.1 and 42.7 respectively. Given that the overall degree of pain relief was the same, we propose that an indication of relative potency of the drugs can be derived from the amounts of analgesic consumed. The meptazinol: pethidine consumption ratios ranged from 4.5:1 to 1.6:1 at varying times after surgery, with a mean over 24 h of 2.4:1. This result seems to be at variance with the conclusion of Paymaster (1977), who suggested that the drugs Were equipotent; however our study and his are not strictly comparable as two different techniques of drug administration were used, and the patients
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Pethidine (n •= 10)
Sweating Pallor Retching Wincing
Pain Drowsiness Dizziness Nausea Elation Depression
groups in either of these ratings. Antiemetics were administered to six patients in the pethidine group, and to eight patients in the meptazinol group. From the collected data it was possible to calculate the mean analgesic consumption for selected intervals within the 24-h period. This information is presented in table V.
TABLE V. Time-related analgesic consumption
TABLE III. 2-4h postoperative observer assessment (number in eachgroup with positive observation). *Assessed by Fisher's Exact Probability test Observations
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ACKNOWLEDGEMENTS
We would like to thank Mrs M. Davies, Miss P. James and Mrs J. Webster for their valuable assistance.
REFERENCES
Chakravarty, K., Tucker, W., Rosen, M., and Vickers, M. D. (1979). Comparison of buprenorphine and pethidine given intravenously on demand to relieve postoperative pain. Br. Med. J., 2, 895. Evans, J. M., Rosen, M., MacCarthy, J., and Hogg, M. I. J., (1976). Apparatus for patient controlled administration of intravenous narcotics during labour. Lancet, 1, 17. Gibbs, J. M., and Johnson, H. D. (1980). A trial of meptazinol for the relief of pain after abdominal surgery. Anaesth. Intern. Care, 8,441. Goode, P. G., and White, A. C.(1971). Some properties of WY 22811, a new analgesic compound. Br.J. Pharm., 43, 462P. Hedges, A., Turner, P., and Wadsworth, J. (1980). A doubleblind comparison of meptazinol with pethidine in postoperative pain. Br. J. Anaesth., 52, 295. Huskisson, E. C. (1974). Measurement of pain. Lancet, 1, 17. Jordan, C , Lehane, J. R., Robson, P. J., and Jones, J. G., (1979). A comparison of the respiratory effects of meptazinol, pentazocine and morphine. Br. J. Anaesth., 51, 497. Oosterlinck, W., and deSy, W. (1975). Preliminary clinical experience with meptazinol, a new analgesic. Curr. Med. Res. Opin., 3, 187. Parkhouse, J., Lambuchts, W., and Simpson, B. R. J. (1961). The incidence of postoperative pain. Br.J. A natsth., 33,345. Paymaster, N. J. (1976). Clinical evaluation of meptazinol, a new analgesic, in postoperative pain. Br.J. Anaesth., 48,599. (1977). Analgesia after operation—a controlled comparison of meptazinol, pentazocine and pethidine. Br. J. Anaesth., 49, 1139. Revill, S. I., Robinson, J. Q., Rosen, M., and Hogg, M. I. J. (1976). The reliability of a linear analogue for evaluating pain. Anaesthesia, 31, 1191. Rosen, M., and Williams, B. (1979). The Valved-Y-Cardiff connector (V. Y. C. Con). Anaesthesia, 34, 882. Swerdlow, M., Starmer, G., and Daw, R. H., (1964). A comparison of morphine and pentazocine in postoperative pain. Br. J. Anaesth., 36, 782.
COMPARAISON DU MEPTAZINOL ET DE LA PETHIDINE ADMINISTRES PAR VOIE INTRAVEINEUSE SUR DEMANDE POUR LE SOULAGEMENT DES DOULEURS POSTOPERATOIRES RESUME
On a compare le meptazinol et la pethidine, au cours d'une etude a double inconnue effecruce sur 20 patients, en utilisant un systeme analgesique sur demande permettant de soulager la douleur apres toute intervention chirurgicale a la partie superieure de Pabdomen. Le degrc d'analgesie, estime d'une maniere subjective, a etc satisfaisant aussi bien avec le meptazinol qu'avec la pethidine; bien que le meptazinol ait produit davantage de nausees que la pethidine (P<0,01), il n'y a eu aucune difference significative du point de vue statistique dans la frequence des autres effets secondaires. Sur une periode de 24 h la consommation moyenne de meptazinol a ete de 2,4 fois plus elevee que celle de pethidine, ce qui laisse penser que lorsqu'il est administrc en injection, le meptazinol est moins puissant que la pethidine.
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were dissimilar. Paymaster administered meptazinol i.m. and investigated a group of patients who had undergone lower abdominal and orthopaedic surgery. Upper abdominal wounds cause severe pain and high analgesic requirement (Parkhouse, Lambuchts and Simpson, 1961; Swerdlow, Starmer and Daw, 1964). One patient using meptazinol was removed from the trial because of inadequate analgesia; before this he recorded the highest drug consumption rate in the group, but still gave high pain, nausea and dizziness scores, despite the administration of an anti-emetic. Examination of this patient's demand record showed that the rate of analgesic consumption had been limited by the pre-set minimum interval between doses. It is probable that if he had been permitted to consume more drug, the degree of pain relief would have been greater. Patients receiving meptazinol had significantly higher scores for nausea than those receiving pethidine. This is consistent with previously published observations (Oosterlinck and deSy, 1975; Gibbs and Johnson, 1980). No evidence of dysphoria was seen with either drug, and no patient reported unpleasant dreams. Meptazinol behaves as a potent analgesic, but larger amounts were consumed than would be expected from previously suggested potency ratios, the most likely explanation being that meptazinol is less potent than pethidine. As meptazinol produced more nausea and, perhaps, also more dizziness than pethidine, it does not seem an improvement on pethidine when administered by intermittent i.v. injection. Meptazinol however, was shown by Jordan and others (1979) to produce less respiratory depression than morphine when given to conscious volunteers by i.m. injection in doses considered to be equianalgesic: meptazinol lOOmg, and morphine lOmg (which is roughly comparable to pethidine 100 mg). If this advantageous comparison with traditional analgesics on i.m. injection holds true when meptazinol is given i.v. in the higher doses (2.4 x) found to be equianalgesic with pethidine in this study, meptazinol may still prove a safe and useful drug in the control of severe pain after surgery.
931 VERGLEICH ZWISCHEN WUNSCHGEMASS ZUR POSTOPERATIVEN SCHMERZLINDERUNG INTRAVENOS GEGEBENEN DOSEN VON MEPTAZINOL UND PETHIDIN
COMPARACION DEL MEPTAZINOL Y DE LA PETIDINA ADMINISTRADAS INTRAVENOSAMENTE SEGUN LA DEMANDA PARA LA GERENCIA DEL DOLOR POSOPERATIVO
ZUSAMMENFASSUNG
Metazinol und Pethidin wurden unter DoppelbhndBedingungen bei 20 Patienten verglichen, bei Verwendung eines Schmerzlinderungssystems auf Wunsch nach Operationen im oberen Unterleib. Das subjektiv bewcrtete Ausmass dcr Schmerzlinderung war bei beiden Drogen zufriedenstellend: obwohl Meptazinol wesentlich mehr Obelkeit bewirkte als Pethidin (P<0,01), gab es keine statistisch wesentlichen Unterschiede in der Haufigkeit anderer Nebenerscheinungen. Ober 24 Stunden betrug de Durchschnittsverbrauch von Meptazinol um 2,4-mal mehr als von Pethidin, was zeigt, das intravends gegebenes Meptazinol weniger stark wirkt als Pethidin.
Se compararon el meptazinol y la petidina en 20 pacientes y bajo condiciones de doble anonimato mediante un sistema anaigesico de administracion segiin la demanda, para aliviar el dolor despues de operacion quiriirjica del abdomen supenor. El grado de anestesia, evaluado subjetivamente, fue el adecuado tanto para el meptazinol como para la petidina; aunque aquel produjo nauseas de una forma mas signincativa que lo hizo la petidina (P< 0,01) no hubo una diferencia estadistica signincativa en la frccuencia de otros efectos secundarios durante 24 horas. El consumo medio de meptazinol fue 2,4 veces mayor que el de petidina, lo que sugiere cuando la administracion es intravenosa aquel es menos potente que csta. Downloaded from http://bja.oxfordjournals.org/ by guest on March 26, 2016