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EFFECTS OF INTRATHECAL MORPHINE, INJECTIED WITH BUPIVACAINE, ON PAIN AFTER ORTHOPAEDIC SURGERY
Br. J. Anauth. (1983), 55, 415
EFFECTS OF INTRATHECAL MORPHINE, INJECTED WITH BUPIVACAINE, ON PAIN AFTER ORTHOPAEDIC SURGERY E. KALSO SUMMARY
The demonstration of opiate receptors in the substantia gelatinosa of the spinal cord (Yaksh and Rudy, 1976) has stimulated interest in the intrathecal administration of morphine in the management of chronic pain and of pain following surgery (Gjessing and Tomlin, 1981; Wang, Nauss and Thomas, 1979). Although the dose of morphine has varied between 0.5 and 20mg.(Sarhii et al., 1979; Wang, Nauss and Thomas, 1979), good analgesia has been achieved with the smaller doses. Since orthopaedic operations are performed frequently under subarachnoid blockade, it was decided to assess the efficacy of a small dose of morphine (0.2 or 0.4 mg), administered with the subarachnoid anaesthetic agent, in the control of postoperative pain. Whether the morphine affected the subarachnoid anaesthesia, perse, was studied also. PATIENTS AND METHODS Patients The programme of the investigation was approved by the hospital Ethics Committee. Informed consent was obtained from 50 orthopaedic patients (table I) in two different age groups: group A (60-80yr^ ASAl-III) and group B (30-50yr, ASA I). All patients had normal respiratory function. Chest x-ray, ECG, spirometry and capillary blood-gas analysis were performed before operation on the older patients. Premedication was with diazepam 5-20 mg orally 1.5-2 h before anaesE. KALSO, M.D., Department of Anaesthesia, Surgical Hospital, Helsinki University Central Hospital, SF-00130 Helsinki 13, Finland.
TABLE I. Characttriitics of thi patients and types of operation. Mtan ages, weights and heights art given (SEM in parentheses) Group
Sex(F/M) Age(yr) Weight (kg) Height (cm) Arthroplasty of hip Arthroplasty of knee Meniscectomy Other
AI
An
AH! BI
BII
7/3 68 (2.1) 73 (3.0) 164 (3.7) 7 2
5/5 67 (1.7) 69 (4.5) 167 (2.7) 5 2
9/1 2/8 68 40 (2.0) (2.0) 63 76 (3.1) (4.4) 160 173 (2.7) (4.3) 9 2
1/9 42 (2.6) 77 (4.9) 175 (3.1) 3
1
3
1
6 2
5 2
thesia and atropine 0.01 mgkg" 1 i.m. about 1 h before anaesthesia. Subarachnoid anaesthesia and concomitant medication Before the spinal injection, Ringer's solution 8 ml kg" 1 was infused rapidly i.v. A similar volume was also administered over a period of about 20 min after the subarachnoid injection of the local anaesthetic. With the patients in a lateral horizontal position the subarachnoid injection was made over about 10 s into interspace L 3 - 4 using a 25-gauge needle and barbotage. The patients were randomly divided into five groups (10 patients in each) according to the amount of morphine hydrochloride (free from preservative) injected with 3 ml of isobaric 0.5% bupivacaine (double-blind): © The Macmillan Press Ltd 1983
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Morphine hydrochloride 0.4mg was administered with isobaric 0.5% bupivacaine intrathecally for orthopaedic surgery and produced good analgesia for about 24 h after operation in both elderly (60-80yr) and middle-aged patients (3O-5Oyr). Morphine 0.2 mg (older patients only) was not as effective in preventing pain after operation, but even this dose postponed the requirement for analgesia. Morphine did not change the quality of spinal anaesthesia. In the older groups the capillary PoOi was increased in two patients receiving morphine 0.2 mg and in one patient receiving 0.4 mg. Severe delayed respiratory depression was not noted. Urinary retention and minor voiding difficulties were the most disturbing side-effects. This complication did not appear to be dose-dependent, and also occurred in patients not receiving morphine.
416 Group AI Group AII
vomiting was recorded. All patients were interviewed by the researcher on the 1st and 2nd days following surgery to detect any side-effects. Pinprick sensation and motor function were tested. Statistical analysis The statistical significance of the differences .between the means was estimated using Student's ftest.
Postoperative analgesia The intensity of pain was tested with a visual analogue scale (a red-coloured wedge, 10 cm x 30 cm, which was divided on the other side to a scale from 0 = no pain to 10 = unbearable pain) (Houde, 1982) 6, 10 and 24 h after the injection of the anaesthetic and every time the patient required an analgesic drug. The test was performed in the recovery room by the researcher and in the ward by trained nurses. Indomethacin suppositories 50-100mg or oxycodone 0.13mgkg" 1 i.m., or both, were prescribed for postoperative pain. The need for analgesics was assessed in the ward by trained nurses and it was recorded for 48 h. All obervation8 were double-blind.
RESULTS Patients and subarachnoid blockade The characteristics of the patients are shown in table I. The operations were mainly arthroplasties in the older age group and meniscectomies in the younger age group (table I). Sensory blockade was sufficient for surgery except for one older low-dose and one older high-dose morphine patient, who felt pain on incision of the skin, although not thereafter. The mean maximum cranial level of analgesia varied between T8 and T6 and there were no significant differences between the groups (table II). Motor blockade was complete, with one exception in the older control group. This patient was lying on the left side during the whole operation and the left leg was not blocked completely. The duration of analgesia was longer (P<0.01) in the younger patients and slightly longer in the older high-dose than in the older control patients (n.s.). None of the other determinants of the regional block differed significantly. Systolic arterial pressure decreased moderately during the induction of anaesthesia (fig. 1). During surgery greater decreases in pressure were observed in the older patients, but these were transient and there was no evidence of hypovolaemic shock. Decreases exceeding 30% of the value before operation were noted in older patients only: eight control patients, seven low-dose arid six high-dose patients. Bradycardia (fig. 1) requiring medication with atropine occurred twice in the control group and once in each of the morphine groups.
Respiratory function and side-effects The respiratory function was observed carefully in the recovery room and later in the ward. Capillary or venous blood-gas analysis was performed on all older patients 3 and 10 h after the subarachnoid injection. About 4 - 5 h after injection the patients were given 100-200 ml of water to drink. Any nausea or
Postoperative pain and its treatment Older patients. The need for analgesic drugs and the intensity of pain at the time of first request in different groups are shown in figure 2. The mean maximum intensities of pain as measured by the visual analogue scale during the first 24 h in different groups were: 7.3 ±0.7 in the control patients, 4.6 ±0.9 in the low-dose and 1.5 ±0.7 in the high-
Sensory and motor blockade, haemodynamics The segmental spread of analgesia was studied by pinprick at 2-min intervals from 4min after the injection up to 30 min. Regression of analgesia after surgery was tested at 30-min intervals until the first sacral spinal segment had recovered. Motor nerve blockade was evaluated simultaneously using Bromage's score (0-3) (Bromage, 1965). Arterial pressure and heart rate were measured at 5-min intervals during the induction of anaesthesia and surgery, and at 15-min intervals in the recovery room. ECG was monitored continuously.
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saline 0.2 ml (older control patients) morphine hydrochloride 0.2 mg (older low-dose patients) Group A III morphine hydrochloride 0.4 mg (older high-dose patients) Group BI saline 0.2 ml (younger control patients) Group BII morphine hydrochloride 0.4 mg (younger morphine patients) The volume added to the bupivacaine before injection was made up with physiological saline to a final volume of 0.2 ml. If a tranquillizer or an analgesic was required, lorazepam 1-4 mg i.v. or fentanyl 0.05-0.1 mg i.v. was given.
BRITISH JOURNAL OF ANAESTHESIA
INTRATHECAL MORPHINE AND BUPIVACAINE
417
TABLE II. Characteristics of spinal blockadt Group
Max. analgesic block (segment)
An
A III
BI
BII
Mean SEM Range Mean SEM Range Mean SEM Range Mean SEM Range
T6 0.9 T10-T2 21 2.2 14-30 12 2.7 4-30 313 15 240-380
T7 1.0 T11-T2 15 1.3 8-20 12 2.1 4-24 339 22 270-490
T6 0.8 T10-T3 20 2.9 6-30 13 2.3 4-30 345 18 250-460
T8 1.1 L1-T3 19 2.1 12-30 20 2.7 10-30 421 35 2$O-635
T7 0.9 T11-T2 16 2.5 8-30 14 2.3 6-30 413 26 290-530
Mean SEM Range
251 7.6 220-290
248 17 200-345
256 15 160-330
266 21 215-370
262 21 170-360
//
induction
150:::
whole operation
E
£ 100' E
I 50-
£::
8 50-
AI
An Group
AI
AH Group
ADI
FIG. 1. Mean changes (± SEM) in systolic arterial pressure and heart rate from preoperative values during induction and surgery in the older patients.
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Time to max. analgesic block (min) Time to max. motor block (min) Time from max. analgetic block to recovery of SI segment (min) Duration of motor block (score 3-0) (min)
AI
BRITISH JOURNAL OF ANAESTHESIA
418 48- • oxycodone
48-
48'
Oindomethacin
~
36-
• 36-
c o
36-
o •
• o 24-
24-
24-
'5.
o
# o
• •
o o
12-
12 •
•
o
6-
6Pain intens.
4 7
59i
•i Patient no
1 2 3 4 5 6 7 8 9 Group
AI
10
tfffli?
1 2 3 4 5 6 7 8 9 10 Group All
1 2345678910 Group Am
FIG. 2. The need for analgesics during the first 48 h after spinal injection and the intensity of pain (visual analogue scale, 0-10) at the time of first request in the older (60-80yr) patients. AI = no morphine, AII = morphine 0.2 mg, A i n — morphine 0.4 mg.
dose patients. The differences between the groups were statistically significant: between high-dose and control groups ( P < 0.001), low-dose and control group (i J <0.05) and between high-dose and lowdose ( P < 0.02). In the control group, eight patients required analgesics within 6 h of the injection of the spinal anaesthetic. The two patients who did not need any analgesics during that time had a long sensory block (380 and 345 min) and both required analgesics within the subsequent 2 h. No patients in the morphine groups needed any analgesics during this time. During the next 18 h eight patients in the low-dose group needed analgesics, two of these managing with indomethacin only. In the high-dose group only two patients (one for an aching back) needed analgesics within the first 24 h. Four patients in the high-dose group managed 48 h without any analgesic and two required indomethacin once. On average, the control group required 3.7 ±0.5 doses of systemic analgesics per patient in the first 48 h, the low-dose morphine patients 3.0 ± 1.0 doses and the high-dose morphine patients 1.0 ± 0.5 doses per patient. The differences were significant (P < 0.001) between the control and high-dose mor-
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*
phine patients and between the high-dose and lowdose morphine patients (P<0.02). There was no statistical difference between the control and lowdose morphine patients. Interestingly, one patient (older high-dose group) had undergone a similar surgical procedure (total hip arthroplasty) 7 months previously. On that occasion she needed oxycodone five times in 24 h after spinal anaesthesia with bupivacaine. On this occasion, after the addition of morphine 0.4mg, she managed with only one dose of oxycodone (fig. 2). Younger patients. The mean maximum intensities of pain during the first 24 h were 5.9+ 1.0 in the control and 2.9 ±0.9 in the morphine group ( P < 0.05). As the duration of sensory blockade was longer in the younger patients only three patients in the control group and none in the morphine group required analgesics within the first 6h after the subarachnoid injection. Within 10 h of the injection eight patients in the control group required analgesics whereas none in the morphine group requested analgesics (fig. 3). The control patients needed on average 3.5 ±0.6 doses of systemic analgesics per patient in the first 48 h, while the
INTRATHECAL MORPHINE AND BUPIVACAINE 48'
1
419 48'
• oxycodone O inciomethaan
36'
36 1
24-
24'
12.
12.
a
I o
6-
t
Pain intens
4
Patient no.
1 2 3 4 5 6 7 8 9 10 Group B I
75
35366
i i i n • i • IT 1 2 3 4 5 6 7 8 9 10 Group B E
FIG. 3. The need for analgesics during the first 48 h after spinal injection and the intensity of pain at the time of first request in the younger (30-50 yr) patients. BI =-no morphine, BII » morphine 0.4mg.
morphine group patients received 2.0 + 0.6 doses per patient. The difference was not significant. One control patient and three morphine group patients managed without any analgesics during the first 48 h. The patient with the greatest need for analgesics in the morphine group complained of severe pain each time he needed analgesics. PCO2 and side-effects
The FCO2 (venous or capillary) was significantly greater (P<0.01) 3 h after the spinal injection than before the operation in all groups (fig. 4). The increase was greatest in the older high-dose morphine group, but the differences between the groups were not significant. No cases of severe respiratory depression were noted although one patient each in the older high-dose (venous PCO1 8.5 kPa) and younger morphine groups (FCO2 7.3 kPa) was cyanotic when observed in the recovery room although the frequency and depth of respiration appeared adequate in both patients. The older high-dose patient had received lorazepam 4 mg during surgery. About 3 h later her FCO2 was 6.7 kPa. Ten hours after the injection the average R:o2 had decreased to within
physiological limits in each group, with the exception of two patients in the older low-dose group (FCCh 8.1kPa and 7.3 kPa, respectively). One of these patients had received oxycodone about 2h earlier, while the other one had not received any analgesic up to this time. As many as seven patients in each of the older control and high-dose morphine groups and five patients in the older low-dose morphine group experienced nausea or vomiting. As many as 14 of these patients had an episode of hypotension (decrease in arterial pressure > 30%) and four patients received fentanyl during the procedure. Five patients had received oxycodone following operation. In the younger patients there was a greater frequency of postoperative nausea and vomiting in the morphine group (table III). Itching occurred only in the morphine groups (three patients, one in each group). Postoperative headache was manifest in the older groups only, but in no instance was it typical post-spinal headache. Micturition difficulties were recorded in both the morphine and control groups during the first 24 h, but not thereafter. Seven patients in the older group
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o o
BRITISH JOURNAL OF ANAESTHESIA
420
6 -
o o
•//
I Before op.
10 Time from spinal injection (h)
FIG. 4. Mean capillary Rx>i values (± SEM) in the older patients.
TABLE III. Occurrence of side-effects (number of patients). *Two and **five additional patients had a urinary catheter placed befort operation. Five of thest patients had a fractured femoral neck and two patients in group A III had been catheteriztd to achieve better control offluid balance Group
Nausea/vomiting Difficulties with micturition Constipation Itching Headache Backache
AI
AH
Am BI
7 3
5 6*
7 2**
1 5
4 7
— — 2 5
— 1 2 2
— 1 4 —
— —
1 1
3
1
BII
already had a urinary catheter in situ before the operation. Five of these had a fractured femoral neck and in two the catheter had been inserted to achieve a better control of fluid balance during rearthroplasties. Five patients in the younger control group had difficulties with micturition, while seven in the younger morphine group complained about voiding difficulties, and three of those needed catheterization on one occasion (table III).
DISCUSSION
Small doses of morphine administered with bupivacaine into the subarachnoid space were found to produce good postoperative analgesia for at least 24 h after orthopaedic surgery. Gjessing and Tomlin (1981) arrived at the same result when they used morphine 0.8 mg in conjunction with tetracaine intrathecally for total hip replacements. Four of 10 patients in the present study who received morphine 0.4mg managed 48 h without any analgesic. In all morphine groups (both older and younger patients) the time interval to the first request for analgesic was longer than in the corresponding control groups. The smaller dose (0.2 mg) did not appear to be totally adequate in relieving pain for the first lOh, the period of time during which the maximum degree of pain following this type of surgery (performed under regional anaesthesia) is experienced (Gjessing and Tomlin, 1979). However, there was a marked difference in the maximum intensity of pain as well as in the need for analgesics between the control and morphine groups. The respiratory depression reported in connection with intrathecal morphine has occurred 10-11 h after the spinal injection (Paulus, Paul and Munson, 1981). This may reflect the time necessary
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4 -
INTRATHECAL MORPHINE AND BUPIVACAINE
421
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for morphine to reach the rostral areas of the CNS. release (Jaffe and Martin, 1975). There were, howTwo patients who had received morphine 0.2 mg ever, no significant differences in the decreases in had an increased PcOj 10 h after the spinal injection, systolic pressures between the morphine and control but no clinical evidence of difficulty with respiration groups during the induction, or during the intrawas observed. The fact that the PcCh at 3 h after the operative or recovery room periods. injection was increased in both the morphine and Doses of 0.2 mg and 0.4 mg of preservative-free control groups suggests an effect of several factors: morphine hydrochloride seem to have no marked lorazepam or fentanyl, or both, during surgery, effect on the subarachnoid block when given simulblood transfusion, episodes of hypotension as a taneously with isobaric 0.5% bupivacaine. The duresult of blood loss and relative hypothermia caused ration of blockade was slightly longer (n.s.) in the by major surgery. In fact, the two older high-dose older morphine groups than in the control group. patients with the greatest PCO2 values at 3 h had been This difference was not found in the younger pagiven fentanyl and lorazepam, respectively, during tients. All other indices were similar in the morsurgery. phine and control groups. Interestingly, the duraOne patient in each of the morphine groups com- tion of spinal analgesia (recovery of S1 segment) was plained of itching. In two the,site was the face, longer in the younger groups than in the older ones. especially the nose, and the itching may have been The reason for this is unclear and deserves further caused by the CNS effects of morphine (Jaffe and study. Martin, 1975). Nausea or vomiting was more frequent in the older than in the younger patients, which may be a ACKNOWLEDGEMENTS result of the different sex-distribution and types of I wish to express my great gratitude to Dr» Per Rosenberg and operation in these groups. The older patients had Marjatta Tuominen for the fruitful discussions during this study. mere major operations which caused more blood loss and a greater frequency of hypotension, both of which cause nausea (Lund, 1971). No correlation REFERENCES was found between the occurrence of nausea and the Abouleish, E., Barmada, M. A.,Nemeto, E. M.,Tung, A., and use of analgesics. Four younger patients who had Winter, P. (1981). Acute and chronic effects of intrathecal received morphine and only one younger control morphine in monkeys. Br. J. Anaesth., 53, 1027. patient suffered from nausea or vomiting. Because Bromage, P. R. (1965). A comparison of the hydrochloride and carbon dioxide salts of lidocaine and prilocaine in epidural of the small numbers involved any conclusions analgesia. Acta Anaeztkesiol. Scand., 16 (Suppl.), 55. about the possible role of morphine may not be Gjessing, J., and Tomlin, P. J. (1979). Patterns of post-operative justified. pain. A study of the use of continuous epidural analgesia in the Surprisingly, many patients in the younger group postoperative period. Anaesthesia, 34, 624. (1981). Postoperative pain control with intrathecal had minor difficulties with micturition. The promorphine. Anaesthesia, 36, 268. longed subarachnoid block together with prolonged R. W. (1982). Methods for measuring clinical pain in maintenance of a supine position (until next morn- Houde, humans. Acta Anaesthesiol. Scand., 74 (Suppl.), 25. ing) certainly had an effect, as five patients out of 10 Jaffe, J. H., and Martin, W. R. (1975). Narcotic analgesics and antagonists; in The Pharmacological Basis of Therapeutics, 5th in the younger control group had difficulties with edn (eds L. S. Goodman and A. Gilman), p. 245. New York, micturition in the first 24 h. Nelson and Katz (1980) Toronto, Macmillan Publ. Co. found no instances of urinary retention in their Lund, P. C.London: (1971). Principles and Practict of Spinal Anesthesia, control group (hyperbaric 1% tetracaine), but five p. 628. Springfield, TlUnnin- Charles C. Thomas. out of seven of those who also received morphine Nelson, W., and Katz, J. (1980). Intrathecal morphine for postoperative pain relief. Antsthtsiology, 53, S218. 0.5 mg had urinary retention. D. A., Paul, W. L., and Munson, E. S. (1981). The maximum decreases in the systolic pressure Paulus, Neurologic depression after intrathecal morphine. Anesthesiolin all older groups were transient and related to ogy, 54, 517. blood loss during surgery. It has been suggested that Samii, K., Feret, J., Harari, A. t and Viars, P. (1979). Selective spinal analgesia. Lancet, 1,1142. the decreases in systolic and diastolic pressures associated with intrathecal morphine in monkeys Wang.J. K.,Nauss,L. A.,and Thomas.J. E.(1979). Pain relief by intrathecally applied morphine in man. Antsthsiology, 50, (Abouleish et al., 1981) are the result of the direct 149. effect of morphine on the vasomotor centre, a vas- Yaksh, T. L., and Rudy, T. A. (1976). Analgesia mediated by a odilator effect on the blood vessels or histamine direct spinal action of narcotics. Science, 192,1357.
BRITISH JOURNAL OF ANAESTHESIA
422 EFFETS DE LA MORPHINE INTRATHECALE, INJECTEE AVEC DE LA BUPIVACAINE, SUR LA DOULEUR CONSECUTIVE A LA CHIRURGIE ORTHOPEDIQUE RESUMB
EFFEKTE VON INTRATHEKALEM MORPHIN, VERABREICHT ZUSAMMEN MIT BUPIVACAIN, AUF SCHMERZEN NACH ORTHOPADISCHEN OPERATIONEN ZUSAMMENFASSUNG
Morphinhydrochlorid 0,4 mg wurde intrathekal zusammen mit isobarem 0,5% igem Bupivacain zu orthopadischen Operationen verabrcicht und erzeugte sowohl bei alteren Patienten (60-80 Jahrc alt) als auch bei Patienten mittleren Alters (30-50 Jahre alt)
EFECTOS DE LA MORFINA INTRATECAL INYECTADA CON BUPIVACAINA SOBRE EL DOLOR DESPUES DE CIRUjlA ORTOPEDICA SUMAIUO
Una dosis de hidrocloruro de morfina de 0,4 mg administrada con bupivacaina isobirica intratecal al 0,5% en cirujia ortopedica produjo una buena analgesia durante 24 h aproximadamente despues de la operacion tan to en pacientes de edad (60-80 anos) corao en lot de edad mediana (30- 50 anos). No fue tan eficaz los 0,2 mg de morfina administrada a los pacientes de edad unicflmente en lo que se refiere a la prevencidn del dolor despues de la operaci6n, pero aun esa dosis atraso la necesidad de analgesia. En los grupos mayores, el PC3 capilar aumento en dot pacientes a quienes se adminiatro 0^2 mg de morfina y en uno con 0,4 mg. No se observd ningiina depresi6n respiratoria atrasada severa. La rctencion de orina y las dificultades menores de vaciamiento constituyeron los efectos secundarios mas molestosos. Esa complicacion no parecia depender de la dosis administrada y ocurrio tambien en pacientes que no recibieron morfina.
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Du chlorhydrate de morphine 0,4 mg a etc administre en meme temps que de la bupivacaine isobare a 0,5% par voie inrrathecale pour des interventions orthopediques. EUe a permis d'obtenir une bonne analgesic postoperatoire pendant pres de 24 h tant chez des patients ages (60-80 ans) que chez des patients d'age moycn (30- SO ans). La dose de 0,2 mg de morphine (utilisee seulement chez les patients plus ages) n'a pas etc aussi efficace pour prevenir U douleur postopetoire, mais a tout de meme permis de retarder 1* demande d'analgesiques. La morphine n'a pas modifie la qualite de la rachianesthesie. Dans les groupes d'ages les plus eleves, la POO2 capillaire s'est elevee chez deux patients recevant morphine 0,2 mg et chez un patient recevant 0,4 mg. Nous n'avoni pas note de depression respiratoirc severe prolongee. Les effcts secondaires les phis genahts ont etc une retention urihaire et des difficultes mictionnelles discretes. Cette complication n'est pas apparue comme dose-d£pendante, et s'est rencontree egaleraent diez des patients n'ayant pas re^u de morphine.
gute postoperative Analgesic fiber 24 Stunden. Morphin 0,2 mg (nur beifflterenPatienten) war bei der Verhiitung postoperativer Schmerzen nicht so effektiv, doch verzogerte auch diese Dosis den Bedarf an Analgetika. Morphin veranderte nicht die Qualitat der Spinalanastesie. In der alteren Gruppe war bei zwei Patienten mit 0,2 mg Morphin und bei einem Patieriten mit 0,4 mg der kapillare PCO2 erholt. Eine stfirkere protrahierte Atemdepression war nicht festzustellen. Eine Urinretention und leichte Entleerungsschwierigkeiten waren die sttirendsten Nebenwirkungen. Diese Komplikation erschien nicht dosisabhfingig und trat auch bei Patienten auf, die kein Morphin erhalten hatten.
EFFECTS OF INTRATHECAL MORPHINE, INJECTED WITH BUPIVACAINE, ON PAIN AFTER ORTHOPAEDIC SURGERY E. KALSO SUMMARY
The demonstration of opiate receptors in the substantia gelatinosa of the spinal cord (Yaksh and Rudy, 1976) has stimulated interest in the intrathecal administration of morphine in the management of chronic pain and of pain following surgery (Gjessing and Tomlin, 1981; Wang, Nauss and Thomas, 1979). Although the dose of morphine has varied between 0.5 and 20mg.(Sarhii et al., 1979; Wang, Nauss and Thomas, 1979), good analgesia has been achieved with the smaller doses. Since orthopaedic operations are performed frequently under subarachnoid blockade, it was decided to assess the efficacy of a small dose of morphine (0.2 or 0.4 mg), administered with the subarachnoid anaesthetic agent, in the control of postoperative pain. Whether the morphine affected the subarachnoid anaesthesia, perse, was studied also. PATIENTS AND METHODS Patients The programme of the investigation was approved by the hospital Ethics Committee. Informed consent was obtained from 50 orthopaedic patients (table I) in two different age groups: group A (60-80yr^ ASAl-III) and group B (30-50yr, ASA I). All patients had normal respiratory function. Chest x-ray, ECG, spirometry and capillary blood-gas analysis were performed before operation on the older patients. Premedication was with diazepam 5-20 mg orally 1.5-2 h before anaesE. KALSO, M.D., Department of Anaesthesia, Surgical Hospital, Helsinki University Central Hospital, SF-00130 Helsinki 13, Finland.
TABLE I. Characttriitics of thi patients and types of operation. Mtan ages, weights and heights art given (SEM in parentheses) Group
Sex(F/M) Age(yr) Weight (kg) Height (cm) Arthroplasty of hip Arthroplasty of knee Meniscectomy Other
AI
An
AH! BI
BII
7/3 68 (2.1) 73 (3.0) 164 (3.7) 7 2
5/5 67 (1.7) 69 (4.5) 167 (2.7) 5 2
9/1 2/8 68 40 (2.0) (2.0) 63 76 (3.1) (4.4) 160 173 (2.7) (4.3) 9 2
1/9 42 (2.6) 77 (4.9) 175 (3.1) 3
1
3
1
6 2
5 2
thesia and atropine 0.01 mgkg" 1 i.m. about 1 h before anaesthesia. Subarachnoid anaesthesia and concomitant medication Before the spinal injection, Ringer's solution 8 ml kg" 1 was infused rapidly i.v. A similar volume was also administered over a period of about 20 min after the subarachnoid injection of the local anaesthetic. With the patients in a lateral horizontal position the subarachnoid injection was made over about 10 s into interspace L 3 - 4 using a 25-gauge needle and barbotage. The patients were randomly divided into five groups (10 patients in each) according to the amount of morphine hydrochloride (free from preservative) injected with 3 ml of isobaric 0.5% bupivacaine (double-blind): © The Macmillan Press Ltd 1983
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Morphine hydrochloride 0.4mg was administered with isobaric 0.5% bupivacaine intrathecally for orthopaedic surgery and produced good analgesia for about 24 h after operation in both elderly (60-80yr) and middle-aged patients (3O-5Oyr). Morphine 0.2 mg (older patients only) was not as effective in preventing pain after operation, but even this dose postponed the requirement for analgesia. Morphine did not change the quality of spinal anaesthesia. In the older groups the capillary PoOi was increased in two patients receiving morphine 0.2 mg and in one patient receiving 0.4 mg. Severe delayed respiratory depression was not noted. Urinary retention and minor voiding difficulties were the most disturbing side-effects. This complication did not appear to be dose-dependent, and also occurred in patients not receiving morphine.
416 Group AI Group AII
vomiting was recorded. All patients were interviewed by the researcher on the 1st and 2nd days following surgery to detect any side-effects. Pinprick sensation and motor function were tested. Statistical analysis The statistical significance of the differences .between the means was estimated using Student's ftest.
Postoperative analgesia The intensity of pain was tested with a visual analogue scale (a red-coloured wedge, 10 cm x 30 cm, which was divided on the other side to a scale from 0 = no pain to 10 = unbearable pain) (Houde, 1982) 6, 10 and 24 h after the injection of the anaesthetic and every time the patient required an analgesic drug. The test was performed in the recovery room by the researcher and in the ward by trained nurses. Indomethacin suppositories 50-100mg or oxycodone 0.13mgkg" 1 i.m., or both, were prescribed for postoperative pain. The need for analgesics was assessed in the ward by trained nurses and it was recorded for 48 h. All obervation8 were double-blind.
RESULTS Patients and subarachnoid blockade The characteristics of the patients are shown in table I. The operations were mainly arthroplasties in the older age group and meniscectomies in the younger age group (table I). Sensory blockade was sufficient for surgery except for one older low-dose and one older high-dose morphine patient, who felt pain on incision of the skin, although not thereafter. The mean maximum cranial level of analgesia varied between T8 and T6 and there were no significant differences between the groups (table II). Motor blockade was complete, with one exception in the older control group. This patient was lying on the left side during the whole operation and the left leg was not blocked completely. The duration of analgesia was longer (P<0.01) in the younger patients and slightly longer in the older high-dose than in the older control patients (n.s.). None of the other determinants of the regional block differed significantly. Systolic arterial pressure decreased moderately during the induction of anaesthesia (fig. 1). During surgery greater decreases in pressure were observed in the older patients, but these were transient and there was no evidence of hypovolaemic shock. Decreases exceeding 30% of the value before operation were noted in older patients only: eight control patients, seven low-dose arid six high-dose patients. Bradycardia (fig. 1) requiring medication with atropine occurred twice in the control group and once in each of the morphine groups.
Respiratory function and side-effects The respiratory function was observed carefully in the recovery room and later in the ward. Capillary or venous blood-gas analysis was performed on all older patients 3 and 10 h after the subarachnoid injection. About 4 - 5 h after injection the patients were given 100-200 ml of water to drink. Any nausea or
Postoperative pain and its treatment Older patients. The need for analgesic drugs and the intensity of pain at the time of first request in different groups are shown in figure 2. The mean maximum intensities of pain as measured by the visual analogue scale during the first 24 h in different groups were: 7.3 ±0.7 in the control patients, 4.6 ±0.9 in the low-dose and 1.5 ±0.7 in the high-
Sensory and motor blockade, haemodynamics The segmental spread of analgesia was studied by pinprick at 2-min intervals from 4min after the injection up to 30 min. Regression of analgesia after surgery was tested at 30-min intervals until the first sacral spinal segment had recovered. Motor nerve blockade was evaluated simultaneously using Bromage's score (0-3) (Bromage, 1965). Arterial pressure and heart rate were measured at 5-min intervals during the induction of anaesthesia and surgery, and at 15-min intervals in the recovery room. ECG was monitored continuously.
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saline 0.2 ml (older control patients) morphine hydrochloride 0.2 mg (older low-dose patients) Group A III morphine hydrochloride 0.4 mg (older high-dose patients) Group BI saline 0.2 ml (younger control patients) Group BII morphine hydrochloride 0.4 mg (younger morphine patients) The volume added to the bupivacaine before injection was made up with physiological saline to a final volume of 0.2 ml. If a tranquillizer or an analgesic was required, lorazepam 1-4 mg i.v. or fentanyl 0.05-0.1 mg i.v. was given.
BRITISH JOURNAL OF ANAESTHESIA
INTRATHECAL MORPHINE AND BUPIVACAINE
417
TABLE II. Characteristics of spinal blockadt Group
Max. analgesic block (segment)
An
A III
BI
BII
Mean SEM Range Mean SEM Range Mean SEM Range Mean SEM Range
T6 0.9 T10-T2 21 2.2 14-30 12 2.7 4-30 313 15 240-380
T7 1.0 T11-T2 15 1.3 8-20 12 2.1 4-24 339 22 270-490
T6 0.8 T10-T3 20 2.9 6-30 13 2.3 4-30 345 18 250-460
T8 1.1 L1-T3 19 2.1 12-30 20 2.7 10-30 421 35 2$O-635
T7 0.9 T11-T2 16 2.5 8-30 14 2.3 6-30 413 26 290-530
Mean SEM Range
251 7.6 220-290
248 17 200-345
256 15 160-330
266 21 215-370
262 21 170-360
//
induction
150:::
whole operation
E
£ 100' E
I 50-
£::
8 50-
AI
An Group
AI
AH Group
ADI
FIG. 1. Mean changes (± SEM) in systolic arterial pressure and heart rate from preoperative values during induction and surgery in the older patients.
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Time to max. analgesic block (min) Time to max. motor block (min) Time from max. analgetic block to recovery of SI segment (min) Duration of motor block (score 3-0) (min)
AI
BRITISH JOURNAL OF ANAESTHESIA
418 48- • oxycodone
48-
48'
Oindomethacin
~
36-
• 36-
c o
36-
o •
• o 24-
24-
24-
'5.
o
# o
• •
o o
12-
12 •
•
o
6-
6Pain intens.
4 7
59i
•i Patient no
1 2 3 4 5 6 7 8 9 Group
AI
10
tfffli?
1 2 3 4 5 6 7 8 9 10 Group All
1 2345678910 Group Am
FIG. 2. The need for analgesics during the first 48 h after spinal injection and the intensity of pain (visual analogue scale, 0-10) at the time of first request in the older (60-80yr) patients. AI = no morphine, AII = morphine 0.2 mg, A i n — morphine 0.4 mg.
dose patients. The differences between the groups were statistically significant: between high-dose and control groups ( P < 0.001), low-dose and control group (i J <0.05) and between high-dose and lowdose ( P < 0.02). In the control group, eight patients required analgesics within 6 h of the injection of the spinal anaesthetic. The two patients who did not need any analgesics during that time had a long sensory block (380 and 345 min) and both required analgesics within the subsequent 2 h. No patients in the morphine groups needed any analgesics during this time. During the next 18 h eight patients in the low-dose group needed analgesics, two of these managing with indomethacin only. In the high-dose group only two patients (one for an aching back) needed analgesics within the first 24 h. Four patients in the high-dose group managed 48 h without any analgesic and two required indomethacin once. On average, the control group required 3.7 ±0.5 doses of systemic analgesics per patient in the first 48 h, the low-dose morphine patients 3.0 ± 1.0 doses and the high-dose morphine patients 1.0 ± 0.5 doses per patient. The differences were significant (P < 0.001) between the control and high-dose mor-
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*
phine patients and between the high-dose and lowdose morphine patients (P<0.02). There was no statistical difference between the control and lowdose morphine patients. Interestingly, one patient (older high-dose group) had undergone a similar surgical procedure (total hip arthroplasty) 7 months previously. On that occasion she needed oxycodone five times in 24 h after spinal anaesthesia with bupivacaine. On this occasion, after the addition of morphine 0.4mg, she managed with only one dose of oxycodone (fig. 2). Younger patients. The mean maximum intensities of pain during the first 24 h were 5.9+ 1.0 in the control and 2.9 ±0.9 in the morphine group ( P < 0.05). As the duration of sensory blockade was longer in the younger patients only three patients in the control group and none in the morphine group required analgesics within the first 6h after the subarachnoid injection. Within 10 h of the injection eight patients in the control group required analgesics whereas none in the morphine group requested analgesics (fig. 3). The control patients needed on average 3.5 ±0.6 doses of systemic analgesics per patient in the first 48 h, while the
INTRATHECAL MORPHINE AND BUPIVACAINE 48'
1
419 48'
• oxycodone O inciomethaan
36'
36 1
24-
24'
12.
12.
a
I o
6-
t
Pain intens
4
Patient no.
1 2 3 4 5 6 7 8 9 10 Group B I
75
35366
i i i n • i • IT 1 2 3 4 5 6 7 8 9 10 Group B E
FIG. 3. The need for analgesics during the first 48 h after spinal injection and the intensity of pain at the time of first request in the younger (30-50 yr) patients. BI =-no morphine, BII » morphine 0.4mg.
morphine group patients received 2.0 + 0.6 doses per patient. The difference was not significant. One control patient and three morphine group patients managed without any analgesics during the first 48 h. The patient with the greatest need for analgesics in the morphine group complained of severe pain each time he needed analgesics. PCO2 and side-effects
The FCO2 (venous or capillary) was significantly greater (P<0.01) 3 h after the spinal injection than before the operation in all groups (fig. 4). The increase was greatest in the older high-dose morphine group, but the differences between the groups were not significant. No cases of severe respiratory depression were noted although one patient each in the older high-dose (venous PCO1 8.5 kPa) and younger morphine groups (FCO2 7.3 kPa) was cyanotic when observed in the recovery room although the frequency and depth of respiration appeared adequate in both patients. The older high-dose patient had received lorazepam 4 mg during surgery. About 3 h later her FCO2 was 6.7 kPa. Ten hours after the injection the average R:o2 had decreased to within
physiological limits in each group, with the exception of two patients in the older low-dose group (FCCh 8.1kPa and 7.3 kPa, respectively). One of these patients had received oxycodone about 2h earlier, while the other one had not received any analgesic up to this time. As many as seven patients in each of the older control and high-dose morphine groups and five patients in the older low-dose morphine group experienced nausea or vomiting. As many as 14 of these patients had an episode of hypotension (decrease in arterial pressure > 30%) and four patients received fentanyl during the procedure. Five patients had received oxycodone following operation. In the younger patients there was a greater frequency of postoperative nausea and vomiting in the morphine group (table III). Itching occurred only in the morphine groups (three patients, one in each group). Postoperative headache was manifest in the older groups only, but in no instance was it typical post-spinal headache. Micturition difficulties were recorded in both the morphine and control groups during the first 24 h, but not thereafter. Seven patients in the older group
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o o
BRITISH JOURNAL OF ANAESTHESIA
420
6 -
o o
•//
I Before op.
10 Time from spinal injection (h)
FIG. 4. Mean capillary Rx>i values (± SEM) in the older patients.
TABLE III. Occurrence of side-effects (number of patients). *Two and **five additional patients had a urinary catheter placed befort operation. Five of thest patients had a fractured femoral neck and two patients in group A III had been catheteriztd to achieve better control offluid balance Group
Nausea/vomiting Difficulties with micturition Constipation Itching Headache Backache
AI
AH
Am BI
7 3
5 6*
7 2**
1 5
4 7
— — 2 5
— 1 2 2
— 1 4 —
— —
1 1
3
1
BII
already had a urinary catheter in situ before the operation. Five of these had a fractured femoral neck and in two the catheter had been inserted to achieve a better control of fluid balance during rearthroplasties. Five patients in the younger control group had difficulties with micturition, while seven in the younger morphine group complained about voiding difficulties, and three of those needed catheterization on one occasion (table III).
DISCUSSION
Small doses of morphine administered with bupivacaine into the subarachnoid space were found to produce good postoperative analgesia for at least 24 h after orthopaedic surgery. Gjessing and Tomlin (1981) arrived at the same result when they used morphine 0.8 mg in conjunction with tetracaine intrathecally for total hip replacements. Four of 10 patients in the present study who received morphine 0.4mg managed 48 h without any analgesic. In all morphine groups (both older and younger patients) the time interval to the first request for analgesic was longer than in the corresponding control groups. The smaller dose (0.2 mg) did not appear to be totally adequate in relieving pain for the first lOh, the period of time during which the maximum degree of pain following this type of surgery (performed under regional anaesthesia) is experienced (Gjessing and Tomlin, 1979). However, there was a marked difference in the maximum intensity of pain as well as in the need for analgesics between the control and morphine groups. The respiratory depression reported in connection with intrathecal morphine has occurred 10-11 h after the spinal injection (Paulus, Paul and Munson, 1981). This may reflect the time necessary
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4 -
INTRATHECAL MORPHINE AND BUPIVACAINE
421
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for morphine to reach the rostral areas of the CNS. release (Jaffe and Martin, 1975). There were, howTwo patients who had received morphine 0.2 mg ever, no significant differences in the decreases in had an increased PcOj 10 h after the spinal injection, systolic pressures between the morphine and control but no clinical evidence of difficulty with respiration groups during the induction, or during the intrawas observed. The fact that the PcCh at 3 h after the operative or recovery room periods. injection was increased in both the morphine and Doses of 0.2 mg and 0.4 mg of preservative-free control groups suggests an effect of several factors: morphine hydrochloride seem to have no marked lorazepam or fentanyl, or both, during surgery, effect on the subarachnoid block when given simulblood transfusion, episodes of hypotension as a taneously with isobaric 0.5% bupivacaine. The duresult of blood loss and relative hypothermia caused ration of blockade was slightly longer (n.s.) in the by major surgery. In fact, the two older high-dose older morphine groups than in the control group. patients with the greatest PCO2 values at 3 h had been This difference was not found in the younger pagiven fentanyl and lorazepam, respectively, during tients. All other indices were similar in the morsurgery. phine and control groups. Interestingly, the duraOne patient in each of the morphine groups com- tion of spinal analgesia (recovery of S1 segment) was plained of itching. In two the,site was the face, longer in the younger groups than in the older ones. especially the nose, and the itching may have been The reason for this is unclear and deserves further caused by the CNS effects of morphine (Jaffe and study. Martin, 1975). Nausea or vomiting was more frequent in the older than in the younger patients, which may be a ACKNOWLEDGEMENTS result of the different sex-distribution and types of I wish to express my great gratitude to Dr» Per Rosenberg and operation in these groups. The older patients had Marjatta Tuominen for the fruitful discussions during this study. mere major operations which caused more blood loss and a greater frequency of hypotension, both of which cause nausea (Lund, 1971). No correlation REFERENCES was found between the occurrence of nausea and the Abouleish, E., Barmada, M. A.,Nemeto, E. M.,Tung, A., and use of analgesics. Four younger patients who had Winter, P. (1981). Acute and chronic effects of intrathecal received morphine and only one younger control morphine in monkeys. Br. J. Anaesth., 53, 1027. patient suffered from nausea or vomiting. Because Bromage, P. R. (1965). A comparison of the hydrochloride and carbon dioxide salts of lidocaine and prilocaine in epidural of the small numbers involved any conclusions analgesia. Acta Anaeztkesiol. Scand., 16 (Suppl.), 55. about the possible role of morphine may not be Gjessing, J., and Tomlin, P. J. (1979). Patterns of post-operative justified. pain. A study of the use of continuous epidural analgesia in the Surprisingly, many patients in the younger group postoperative period. Anaesthesia, 34, 624. (1981). Postoperative pain control with intrathecal had minor difficulties with micturition. The promorphine. Anaesthesia, 36, 268. longed subarachnoid block together with prolonged R. W. (1982). Methods for measuring clinical pain in maintenance of a supine position (until next morn- Houde, humans. Acta Anaesthesiol. Scand., 74 (Suppl.), 25. ing) certainly had an effect, as five patients out of 10 Jaffe, J. H., and Martin, W. R. (1975). Narcotic analgesics and antagonists; in The Pharmacological Basis of Therapeutics, 5th in the younger control group had difficulties with edn (eds L. S. Goodman and A. Gilman), p. 245. New York, micturition in the first 24 h. Nelson and Katz (1980) Toronto, Macmillan Publ. Co. found no instances of urinary retention in their Lund, P. C.London: (1971). Principles and Practict of Spinal Anesthesia, control group (hyperbaric 1% tetracaine), but five p. 628. Springfield, TlUnnin- Charles C. Thomas. out of seven of those who also received morphine Nelson, W., and Katz, J. (1980). Intrathecal morphine for postoperative pain relief. Antsthtsiology, 53, S218. 0.5 mg had urinary retention. D. A., Paul, W. L., and Munson, E. S. (1981). The maximum decreases in the systolic pressure Paulus, Neurologic depression after intrathecal morphine. Anesthesiolin all older groups were transient and related to ogy, 54, 517. blood loss during surgery. It has been suggested that Samii, K., Feret, J., Harari, A. t and Viars, P. (1979). Selective spinal analgesia. Lancet, 1,1142. the decreases in systolic and diastolic pressures associated with intrathecal morphine in monkeys Wang.J. K.,Nauss,L. A.,and Thomas.J. E.(1979). Pain relief by intrathecally applied morphine in man. Antsthsiology, 50, (Abouleish et al., 1981) are the result of the direct 149. effect of morphine on the vasomotor centre, a vas- Yaksh, T. L., and Rudy, T. A. (1976). Analgesia mediated by a odilator effect on the blood vessels or histamine direct spinal action of narcotics. Science, 192,1357.
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422 EFFETS DE LA MORPHINE INTRATHECALE, INJECTEE AVEC DE LA BUPIVACAINE, SUR LA DOULEUR CONSECUTIVE A LA CHIRURGIE ORTHOPEDIQUE RESUMB
EFFEKTE VON INTRATHEKALEM MORPHIN, VERABREICHT ZUSAMMEN MIT BUPIVACAIN, AUF SCHMERZEN NACH ORTHOPADISCHEN OPERATIONEN ZUSAMMENFASSUNG
Morphinhydrochlorid 0,4 mg wurde intrathekal zusammen mit isobarem 0,5% igem Bupivacain zu orthopadischen Operationen verabrcicht und erzeugte sowohl bei alteren Patienten (60-80 Jahrc alt) als auch bei Patienten mittleren Alters (30-50 Jahre alt)
EFECTOS DE LA MORFINA INTRATECAL INYECTADA CON BUPIVACAINA SOBRE EL DOLOR DESPUES DE CIRUjlA ORTOPEDICA SUMAIUO
Una dosis de hidrocloruro de morfina de 0,4 mg administrada con bupivacaina isobirica intratecal al 0,5% en cirujia ortopedica produjo una buena analgesia durante 24 h aproximadamente despues de la operacion tan to en pacientes de edad (60-80 anos) corao en lot de edad mediana (30- 50 anos). No fue tan eficaz los 0,2 mg de morfina administrada a los pacientes de edad unicflmente en lo que se refiere a la prevencidn del dolor despues de la operaci6n, pero aun esa dosis atraso la necesidad de analgesia. En los grupos mayores, el PC3 capilar aumento en dot pacientes a quienes se adminiatro 0^2 mg de morfina y en uno con 0,4 mg. No se observd ningiina depresi6n respiratoria atrasada severa. La rctencion de orina y las dificultades menores de vaciamiento constituyeron los efectos secundarios mas molestosos. Esa complicacion no parecia depender de la dosis administrada y ocurrio tambien en pacientes que no recibieron morfina.
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Du chlorhydrate de morphine 0,4 mg a etc administre en meme temps que de la bupivacaine isobare a 0,5% par voie inrrathecale pour des interventions orthopediques. EUe a permis d'obtenir une bonne analgesic postoperatoire pendant pres de 24 h tant chez des patients ages (60-80 ans) que chez des patients d'age moycn (30- SO ans). La dose de 0,2 mg de morphine (utilisee seulement chez les patients plus ages) n'a pas etc aussi efficace pour prevenir U douleur postopetoire, mais a tout de meme permis de retarder 1* demande d'analgesiques. La morphine n'a pas modifie la qualite de la rachianesthesie. Dans les groupes d'ages les plus eleves, la POO2 capillaire s'est elevee chez deux patients recevant morphine 0,2 mg et chez un patient recevant 0,4 mg. Nous n'avoni pas note de depression respiratoirc severe prolongee. Les effcts secondaires les phis genahts ont etc une retention urihaire et des difficultes mictionnelles discretes. Cette complication n'est pas apparue comme dose-d£pendante, et s'est rencontree egaleraent diez des patients n'ayant pas re^u de morphine.
gute postoperative Analgesic fiber 24 Stunden. Morphin 0,2 mg (nur beifflterenPatienten) war bei der Verhiitung postoperativer Schmerzen nicht so effektiv, doch verzogerte auch diese Dosis den Bedarf an Analgetika. Morphin veranderte nicht die Qualitat der Spinalanastesie. In der alteren Gruppe war bei zwei Patienten mit 0,2 mg Morphin und bei einem Patieriten mit 0,4 mg der kapillare PCO2 erholt. Eine stfirkere protrahierte Atemdepression war nicht festzustellen. Eine Urinretention und leichte Entleerungsschwierigkeiten waren die sttirendsten Nebenwirkungen. Diese Komplikation erschien nicht dosisabhfingig und trat auch bei Patienten auf, die kein Morphin erhalten hatten.