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A comparison of epidural tramadol and epidural morphine for postoperative analgesia
The present study compared epidural tramadol with epidural morphine for postoperative analgesia in 20 patients undergoing major abdominal surgery. Intraoperatively, the patients were anaesthetized by a balanced technique of general anaesthesia combined with lumbar epidural lidocaine. In ten of the patients 100 mg tramadol diluted in 10 ml normal saline was also injected epidurally, while 4 mg epidural morphine was used in the other ten patients. In all patients, the visual analogue pain score, PaO2, PaC02 and respiratory rate were monitored every hour for the first 24 hr postoperatively. In both the trarnadol and morphine groups, the mean hourly pain scores ranged from 0.2 + 0.6 to 1.4 5:2.5 throughout the period of observations, However, the mean Pa02 was decreased postoperatively in the epidural morphine group, while no change was observed in the epidural tramadol group. The maximal decrease of Pa02 in the epidural morphine group was observed at the tenth hour postoperatively, when it decreased to 72.8 q- 10.3 mmHg. This was not associated with any increase in PaCO2 or a decrease of respiratory rate, suggesting that hypoxaemia rather than hypercarbia or decreased respiratory rate may be an earlier indicator of respiratory depression in patients breathing room air without oxygen supplementation. The absence of clinically relevant respiratory depression following epidural tramadol compared with epidural morphine may be attributed to the different mechanisms of their analgesic action. The results suggest that epidural tramadol can be used to provide prolonged postoperative analgesia without serious side effects.

Anis Baraka MBBChDADM MD FRCAnaesth(Hon), Samar Jabbour MD, Maroun Ghabash MD, Antoun Nader MD, Ghattas Khoury MD, Abla Sibai us

Key w o r d s

Cette ~tude compare le tramadol ?t la morphine donn~e par voie ~pidurale pour l'analgdsie postopdratoire de 20 patients subissant une chirurgie abdominale majeure. Les patients sont anesthesias par une technique balanc~e, combin~e h une ~pidurale lombaire d la lidoca~ne. Chez dix des patients, tramadol 100 mg dilu~ de 10 ml de liquide physiologique est ~galement injectd par voie ~pidurale, tandis que morphine ~pidurale 4 mgest inject~e aux autres patients. Chez tousles patients, une ~chelle visuelle analogue de la douleur, la Pa02, la PaC02 et lafr~quence respiratoire sont mesurdes chaque heure pendant les 24 premibres heures postopkratoires. Autant dans le groupe tramadol que dans le groupe morphine, la valeur moyenne de l'dvaluation de la douleur se situ~ de 0,2 + 0,6 d 1,4 + 2,5 pendant toute la pdriode dbbservation. La PaO2 moyenne est cependant diminu~e en postop~ratoire clans le groupe dpidurale ,~ la morphine tandis qu'aucun changement n'est observ~ dans le groupe ~pidurale au tramadol. La diminution maximum de la PaO2 dans le groupe ~pidurale h la morphine se situe la dixibme heure postop~ratoire, et atteint une valeur de 72,8 -I- 10,3 mmHg. Elle n'est associ~e ~t aucune augmentation de PaCO2 ni ?tune diminution de fr~quence respiratoire, sugg~rant que lhypox~mie plutdt que l'hypercapnie vu la diminution de fr~quence respiratoire peut ~tre un indice pr~coce de la d~pression. respiratoire chez des patients respirant l'air ambiant sans suppl~ment dbxygbne. L'absence de d~pression respiratoire cliniquement significative aprbs une ~pidurale au tramadol par rapport ?t une ~pidurale h la morphine peut ~tre attribute h un mdcanisme d'action analgdsique diffdrent. Ces r~sultats suggbrent qu'une ~pidurale au tramadol tfeut ~tre utilis~e pour procurer une analg~sie post-op~ratoire prolongde sans effets secondaires s~rieux.

ANALGESIA:postoperative; ANALGESICS:morphine, tramadol; ANAESTHETICTECHNIQUES:epidural. From the Departments of Anesthesiology,Surgery and Epidemiology, and Biostatistics, American University of Beirut, Beirut-Lebanon. Address correspondence to: Anis Baraka, Department of Anesthesiology, American University of Beirut, Beirut Lebanon.
Accepted for publication December 1, 1992.
CAN J ANAESTH 1993 / 40:4 / pp 308-13

Epidural morphine has been used for postoperative analgesia. However, many side effects such as nausea, vomiting, pruritus, urinary retention, and delayed respiratory depression have been reported. 1-6 Although rare, delayed resporatory depression is the most serious complication and may occur several hours after the administration of epidural morphine. One(m-methylphenyl)-2-(dimethylaminoethyl)-cyclohexan-l-01(tramadol; Tramal*) 7 is a new synthetic opioid

PaCO2 and respiratory rate were compared in each group with the corresponding control values monitored prior to induction of anaesthesia. and tracheal intubation was facilitated with succinylcholine 1.9. The following variables were assessed by a chief resident who was blind to the epidural narcotic used.4 + 8. ASA physical status II and III.5 mg.8 Jr 12.8 6:4 70 + 12. Anaesthesia was induced with thiopentone 5 mg. tramadol has been reported to depress the spinal nociceptive receptors in the rat.Aorto-femoralgrafting .0 3 4 3 58. ~2 The present study compared epidural tramadol with epidural morphine for postoperative analgesia in patients undergoing major abdominal surgery." while 10 denotes "worst pain imaginableY Respiration The depressant effects of epidural morphine or epidural tramadol on respiration were assessed by monitoring the arterial PO2 and PCO2. nausea and vomiting. an epidural catheter was inserted. in the lateral decubitus position. it was not possible to assess its incidence in our patients who had an indwelling bladder catheter during the first 24 hr. All data are presented as mean values + SD.2. 130 denotes "no pain. In man. and were introduced to the visual analogue pain scale. No parenteral analgesic drugs were given intraoperatively. The mean hourly values of PaO2. as well as the changes of arterial blood gases during the first 24 hr postoperatively. Analysis of variance (ANOVA) for repeated measurements using SPSS programme was conducted to compare the hourly pain scores.05 was considered significant.4 mg scopolamine im 45 min before surgery. kg -I.05 mg.: EPIDURALTRAMADOL drug and has been advocated as an analgesic without respiratory depression when used parenterally. Methods The investigation was approved by the Institution Research Committee. Comparison of . with vecuronium as a muscle relaxant. Patients in Group A also received via the epidural catheter 100 mg tramadol diluted in 10 ml normal saline. kg-l). Twenty patients. neuromuscular blockade was reversed with a mixture of atropine (0.o-L3 or L3-L4 level. A catheter was inserted into the radial artery of all patients. and the trachea was extubated. PaO2. the patients were informed about the purpose of the study. kg -t.Baraka et al. Although urinary retention is a recognized side effect of epidural narcotics. The type of surgery and the demographic data of the two groups were simUar (Table I). r0 indicating that. as well as the respiratory rate every hour during the fast 24 hr postoperatively. Group A consisted of ten patients receiving epidural tramadol. nausea and vomiting during the first 24 hr postoperatively was compared in the two groups. kg -l) and neostigmine (0. which was followed by spontaneous breathing of room 309 TABLEI Demographic data and typeof surgeryin the epidural tramadoland epiduralmorphinegroups Group A (10) tramadol GroupB (10) morphine Age (yr) Male/female Weight(kg) Surgerytime(hr) Type of surgery: . and an informed consent was obtained from all patients. at the I.RadicalCysteetomy 59. R ~ Linear analogue pain score The mean hourly pain scores in the epidural tramadol and the epidural morphine groups during the fast 24 hr postoperatively are shown in Figure 1. Patients received oxygen by face mask during the first 30-45 min following surgery. P < 0. 12 All patients received premedication with 0.3 9:1 62. Intermittent positive-pressure ventilation was continued throughout the surgical procedure. The report also compared the incidence of side effects such as itching. The patients were randomly divided into two groups A and B. On the evening of the operation.9 Recently. while Group B consisted of ten patients receiving epidural morphine. PaCO2.4 3 4 3 air with no oxygen supplementation. 8. and respiratory rate values. Anaesthesia was mainmined with N20:O2 (2:1).6 5 4. preliminary reports have shown that epidural tramadol can provide postoperative analgesia safely without any serious side effects. like morphine. 't it acts at the spinal level. All patients were monitored for 24 hr postoperatively in the postoperative care unit. An initial dose of 5 ml lidocaine 2% was injected via the epidural catheter.02 mg.2 4.Repairof infrarenalaortic aneurysm . while those in Group B received 4 mg morphine in 10 ml normal saline. In the operating room. Other side effects The incidence of itching. Pain score Intensity of postoperative pain during the first 24 hr postoperatively was assessed every hour using the linear analogue pain score. were scheduled for elective major abdominal surgery. to be followed by an additional 10 ml. At the end of the operation.8 4 + 1.

Arterial blood gases During the first 24 hr postoperatively. The mean hourly PaCO2 values and the mean res- Side effects One patient in the tramadol group had itching versus two patients in the morphine group.5 in both groups (NS).6 to 1. The maximal decease of PaO2 in the morphine group was observed at the tenth hour postoperatively. No differences were noted between the two groups (Table II). compared with preoperative control values. when the mean PaO2 was 72. can provide adequate and prolonged postoperative . the hourly pain scores demonstrated good pain relief in both groups with mean pain scores ranging from 0.4 + 2.8 + 10.2 -t0. piratory rates did not change in either group.3 mmHg (Figure 2). Two patients in the tramadol group had nausea and vomiting versus four patients in the morphine group. the mean PaOz did not change in the epidural tramadol group. Discussion The present report shows that epidural tramadol. like morphine. FIGURE 3 The mean PaCO 2 in the epidural tramadol and the epidural morphine groups during the first 24 hr after surgery. while it decreased in the morphine group from the sixth hour postoperatively. FIGURE 4 The mean respiratory rate per minute in the epidural tmmadol and the epidural morphine groups during the first 24 hr after surgery.310 CANADIAN JOURNAL OF ANAESTHESIA FIGURE I The mean pain scores in the epidural tramadol and the epidural morphine groups during the first 24 hr after surgery. FIGURE 2 The mean PaO 2 in the epidural tramadol and the epidural morphine groups during the first 24 hr after surgery. (Figures 3 and 4).

in particular depression of the CO2 response curve. and hence respiratory depression can manifest . The limited body oxygen stores as well as activation of the hypoxic drive may explain our findings which suggest that hypoxaemia rather than elevation of PaCO2 or a decrease of respiratory rate may be an early signal of respiratory depression following epidural morphine in patients breathing room air without oxygen supplementation. was not followed by delayed respiratory depression. Morphine acts selectively as an opiate agonist. However. the incidence of itching. In the presence of supplemental oxygen. is The reduction of FRC and the consequent alteration in the relationship of closing volume to FRC 19 can result in ventilation-perfusion mismatching. beneath the antero-lateral surface of the medulla. diaphragmatic function is also impaired and additional splinting by abdominal distension and pain may promote pulmonary atelectasis. suggests that non-opioid receptors mechanisms of action may contrib- Group A (10) tramadol Itching Nausea/vomiting 1 2 Group B (It)) morphine 2 4 analgesia in patients undergoing major abdominal surgery. On the other hand. i The immediate postoperative period is a potentially high risk time for the occurence of hypoxaemia. calculation of the CO2 response curve is time-consuming and requires patient cooperation. and clinically important. however. which can produce analgesia as well as respiratory depression. 8. ~ More recent work. without compromising the PaO2. Many studies of epidural morphine have failed to detect clinically important respiratory depression. the body oxygen stores are limited compared with the very large carbon dioxide stores.2 mm.14 Pulse oximetry may be useful as a simple noninvasive technique for continuous and long-term monitoring of oxygenation during the postoperative period in patients receiving epidural narcotics. I Altered chemosensitivity.Baraka el al. as shown by the present and previous reports. The maximal decrease of mean PaO2 in the morphine group was observed at the tenth hour postoperatively. it has not been determined Whether an altered CO2 response curve is a reliable prediction of transient apnoea or hypoventilation. Also. but without decrease of respiratory rate or increase of PaCO2. 2~ The respiratory depressant effects of opioid analgesia also have an important role in the production of postoperative hypoxaemia. 13 Also. Also. saturation may be well maintained despite hypoventilation or apnoeic episodes.23Tramadol is a weak agonist at all types of opioid receptors with some selectivity for mureceptors. However. the PaO2 was decreased from the sixth hour postoperatively. However. resulting in a high CSF concentration of morphine available to move cephalad to reach supra-spinal structures and produce delayed respiratory depression. Patients in this group showed no changes of PaO2 or PaCO2 during the first 24 hr postoperatively whereas. 21 Mu receptors mediate analgesia and respiratory depression. yet have a normal respiratory rate. respiratory depression than equi-analgesic doses of parenteral tramadol.J5 In contrast with morphine which acts selectively as an opiate agonist. However. however. 15 and can partially counteract the decrease of respiratory rate and/or tidal volume. 17 Hypoxaemia in the early postoperative period is likely to be caused partly by the reduction in functional residual capacity (FRC) secondary to anaesthesia and surgery. 14 This may cause an erroneous diagnosis of shunting rather than hypoventilation. acute alveolar hypoventilation can rapidly decrease the arterial PO2. bathed in the CSE 1. ~ as well as a non-opioid receptor mechanism of action.: EPIDURAL TRAMADOL TABLE II Side effects during the first 24 hr after surgery in the epidural tramadol and the epidural morphine groups 311 by an increased PaCO2. Following upper abdominal surgery. when the PaO2 was 72. nausea and vomiting was similar in the two groups. Whether kappa agonist activity contributes to respiratory depression is uncertain. 17 Previous clinical reports have also shown that parenteral morphine results in greater. is considered a sensitive index of respiratory depression. hypoxaemia may trigger the hypoxic drive via the peripheral chemoreceptors. because of the highly ionized and hydrophilic nature of morphine. breathing oxygen causes a substantial increase in the alveolar oxygen concentration. despite the relatively high dose used. 22. while kappa receptors mediate analgesia and sedation. 0. Morphine is a mu and kappa agonist. epidural tramadol. the analgesic effects of tramadol are mediated by an opioid.3 mmHg.8 +_ 10. 1 Monitoring respiratory rate is the simplest form of monitoring.9 The absence of respiratory depression following epidural or parenteral tramadol compared with epidural or parenteral morphine may be attributed to the different mechanisms of their analgesic actions. Also. ~6 The pathogenesis of postoperative hypoxaemia is multifactorial. egress of the drug transferred to the spinal fluid following its epidural administration will be slow. 2 probably by its action on the central chemoreceptors which lie very superficially. 6 Also. while the PaCO2 may still be within the normal range. patients may be hypoxaemic and/or hypercarbic. in the epidural morphine group. Therefore. PaCO2 has been considered the essential index of alveolar ventilation.

Rudy TA. Goldman MD. Respiratory depres- C A N A D I A N J O U R N A L OF A N A E S T H E S I A wirkenden Analgetikum. Norman PH. Intrathecal and epidural admin- istration of opioids. 4 Bromage PR.. 23 Dhasmana KM. without early or delayed clinical respiratory depression. Cruse PJ. our report shows that epidural tramadol can provide adequate and prolonged postoperative analgesia. including tolerance and . Sandier AN. Br J Anaesth 1992. Tramadol inhibits noradrenaline uptake and stimulates serotinin release. it is interesting to note that a single dose of epidural morphine or epidural tramadol as the sole analgesic agent could provide in our population such prolonged and low pain scores during the fast 24 hr after surgery. Erdmann W. without inducing respiratory depression. 192: 1357-8. This observation confirms our previous study which showed that the requirement for postoperative analgesics was lower in patients operated upon during and after the Lebanese war than in those patients operated upon before the war. In contrast. 63: 8-14. Arzneimittel-Forschung1978. Hamburg. Previous reports have shown that the combination of an opioid and non-opioid such as an a2-adrenergic agonist may act synergistically for the analgesic response without potentiating respiratory depression. Analgesicpotency of epidural tramadol after abdominal surgery. 37: 933-42. 127: 431-6.. Epidural mor- phine causes delayed and prolonged ventilatorydepression. a decrease of PaO2 rather than an increase of PaCO2 or a decrease in respiratory rate may be an early indicator of respiratory depression following epidural morphine. Annu Rev Pharmacol Toxicol 1985. Hogg MIJ The reliability of a linear analogue for evaluating pain. Stuart B. elderly patients may requires less narcotics than young patients. 9 VickersMD.. In: Nunn JF (Ed. Fridericks E. Eur J Pharmacol 1987. 8 Houmes R-JM.a n experimentaland clinicalstudy. The physiologyand pharmacology of spinal opiates. Sandier AN. Anaesthesia 1992. WattwilM. Am Rev Respir Dis 1983. Analgesia mediated by a direct spinal action of narcotics. Mather LE. et respite finem: whatever you do. Parikh RK. FelgenhauerF. Pharmalogische Untersuchungenvon tramadol. 5th World Congress on Pain. 10: 289-93.). Clement JL Thompson WR. Receptor binding. 3 Knill RL. 38: 877-80. Lachmann B. Ventilatoryfailure. Arzneimittel-forschung1988. Voets MA. Read M. Chung Kuo Yao Li Hsueh Pan 1989. 47: 291-6. Anesth Analg 1992. The price of intraspinal narcotic analgesia: basic constraints (Editorial). 22 Hennies HH. 2 Cousins M J. Effects of the analgesic agent tramadol in normal and arthritic rats: comparison with the effectsof differentopioids. 14 Nunn JF. prudenter agas. 11 Yaksh TL. 25: 433-62. Erdmann W. 64: 507-14. 15 Duffin . 10 Carlsson K-H. do cautiously. Respiratory depression after epidural morphine . Zindler M. Can J Anaesth 1989. Tramadol: pain relief by an opioid without depres- sion and spinal opioids. Loh L. Wust H.26 Finally. analgesic and antitussivepotency of tramadol and other selected opioids. 38: 740-6. 24 Kayser V. Verkaaik A. Daley MD. Szekely SM. 2s In conclusion. 17 Reeder MK. 379-91. Warth L. epidural morphine may be followed by delayed respiratory depression as evidenced by the decrease of PaO2. Anesthesiology1984. einem stark sion of respiration. Rosen M. 7 Friderichs E. 13 Revill SI.and look to the end (Editorial). The chemoreflexcontrol of breathing and its measurement. This report suggests that in patients breathing room air without oxygen supplementation. 21 Yaksh TL. Noueihed R. Anesth Analg 1981. 23. 25. References 1 Etches RC. The role of airway closure in postoperativehypoxaemia. Quidquid agas. Can Anaesth Soc J 1981. 18 Hedenstierna G. Yoshizumi J. Rosenal TW. 61: 276--310. Diaphragm function after upper abdominal surgery in humans. Br J Anaesth 1973. Applied Respiratory Physiology. Anaesthesia 1976. 60: 461-3. 37: 527-9. Hypoxaemiain adults in the post-anaesthesiacare unit. 28: 122-34. 16 Daley MD. Banerjee AK. Guenter CA. Efficacyand safety of tramadol versus mor- phine for moderate and severe postoperativepain with special regard to respiratory depression. London: Butterworths. Can J Anaesth 1990. Besson J.3rd ed. 20 Ford GT. 139: 1-10.. 31: 1191-8. and these are transmitters in the descending pathways which enhance analgesia. Rating W. Anaesthesia 1982.40. The absence of respiratory depression following epidural tramadol compared with morphine may be attributed to their different mechanisms of action. 12 Chrubasik J. Robinson JO. 5 Morgan M. Gas exchange during anaesthesia. Pain (1987) Suppl 4. Guilbaud G. Whitelaw WA. Jurna Z Effectsof tramadol on motor and sensory responses of the spinal nociceptivesystem in the rat. 68: 23-6. Abstract No 296. 6 Rawal N. 27 Also. the maximal decrease of PaO2 was observed at the tenth hour postoperatively. Br J Anaesth 1990. Can J Anaesth 1991. 75: 510-4. 36: 165-85. 1987.1. 1987. et at Postoperative hypoxaemia after major abdominal vascular surgery. 19 Alexander JL Spence AA. Analgesic effect of tramadol in the rat. Schneider J. O'Flaherty D. Jongschaap P. 45: 34. Anesth Analg 1984. Science 1976. 28: 537-43. Osterloh G. Colmenares ME.312 ute to the analgesic profde.24 The non-opioid mechanisms may potentiate the analgesia of epidural tramadol.

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