Service dAnesthésie-Réanimation, Hôpital Tenon, Assistance Publique Hôpitaux de Paris, 4 rue de la Chine, F-75970 Paris cedex 20, France*Corresponding author
Presented in abstract form at the annual meeting of the European Society of Anaesthesiologists, Amsterdam, May 1999.
Accepted for publication: August 11, 2000
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Abstract |
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Br J Anaesth 2001; 86: 23640.
Keywords: analgesics opioid, morphine; analgesics opioid, sufentanil; analgesia, post-operative; surgery, thoracic
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Introduction |
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The intrathecal administration of morphine in post-operative patients was first reported in 1979.2 Although in the following years this technique was shown to provide effective analgesia of long duration in the post-operative period, its use has been restricted compared with epidural analgesia, because of the alleged higher incidence of side-effects with intrathecal opioids.3 Nevertheless, intrathecal opioid administration has been investigated more recently in the context of major surgery, especially cardiac.410
The onset and duration of action of intrathecal and epidural opioids depend on their lipid solubility.11 Intrathecal morphine has a long duration of action but a slow onset of action. On the contrary, lipid-soluble opioids such as fentanyl and sufentanil have a rapid onset but shorter duration of action. Combining epidural morphine and sufentanil may produce analgesia of rapid onset and long duration.12 13 Intrathecal administration of both drugs may produce a similar profile and therefore we performed a study of this technique in patients after thoracic surgery.
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Patients and methods |
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Patients were allocated to a control group or a group given intrathecal morphine and sufentanil (SM group). Randomization was performed on the morning of surgery. In both groups, premedication consisted of flunitrazepam 1 mg. Anaesthesia was induced with propofol 2.5 mg kg1 and sufentanil 0.5 µg kg1. Tracheal intubation was facilitated by atracurium 0.5 mg kg1. Anaesthesia was maintained with isoflurane (end-tidal concentration 0.81.5%). Any increase in arterial pressure (systolic arterial pressure >130 mm Hg or >150% of the preinduction value) and tachycardia (>120 min1 or >150% of the preinduction value) led to the administration of sufentanil 0.5 µg kg1. A pulsed warm-air device (Bair Hugger®, Augustine Medical Inc., Eden Prairie, MN, USA) was applied to the lower body to maintain body temperature during surgery. Indicators for extubation were recovery from anaesthesia, spontaneous breathing (end-tidal carbon dioxide 42 mm Hg), a stable haemodynamic condition and normothermia.
In the SM group, intrathecal administration of opioids was performed before surgical incision through a 24 G Sprotte needle inserted in the L34 or L45 vertebral interspace, in the lateral position. Patients received 4 ml of a solution containing sufentanil 20 µg and morphine 200 µg. In the control group, patients had the skin prepared with antiseptic and covered with an adhesive dressing in an identical manner to the intrathecal group.
When patients complained of pain in the recovery room, they received a titrated dose of morphine (2 mg bolus at 5 min intervals) until the visual analogue scale (VAS) score was <30. They were then given access to an i.v. patient-controlled analgesia (PCA) pump (APM®, Abbott, Rungis, France) delivering 1 mg morphine bolus doses with a 7 min lockout interval (maximum dose 30 mg 4-hourly). Morphine was diluted to 1 mg ml1 in a solution also containing droperidol 5 mg in 50 ml. PCA was maintained for 72 h. After 3 days, analgesia was maintained by subcutaneous administration of morphine.
Post-operative pain was evaluated by an anaesthetist blinded to treatment groups, using a VAS graded from 0 (no pain) to 100 (worst pain imaginable) and a verbal rating scale (VRS) (0=no pain; 1=mild; 2=moderate; 3=severe; 4=unbearable). Measurements were performed at rest and on coughing with the VAS, and at rest only with the VRS, 1, 2, 4, 6, 12, 18, 24, 36, 48 and 72 h after arrival in the recovery room.
Side-effects, including respiratory depression (respiratory rate <8 b.p.m.), sedation (not rousable except by persisting verbal or tactile stimulation), urinary retention (requiring transient bladder catheterization), nausea, vomiting and pruritus, were recorded at the same intervals.
Spirometry was performed for the determination of forced expiratory volume in 1 s (FEV1), peak expiratory flow rate (PEFR) and forced vital capacity (FVC), before surgery and at 6, 24, 48 and 72 h after surgery.
The main goal of the study was to demonstrate a 50% difference in i.v. morphine consumption between the two groups. Assuming that mean (SD) morphine consumption would be about 50 (25) mg per 24 h, we calculated that a sample of 20 patients would be enough to detect such a difference with a type I error of 0.05 and a type II error of 0.10. Statistical analysis was by unpaired Students t-test for comparison of patient characteristics, duration of surgery, i.v. sufentanil and morphine doses and extubation delay. Two-way analysis of variance and the Scheffé F-test were used to compare VAS scores. The MannWitney rank sum test was used to analyse morphine consumption and VRS scores. P<0.05 was considered significant.
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Results |
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Discussion |
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Only three previous double-blind, randomized studies have assessed the use of intrathecal opioids for post-thoracotomy analgesia, despite the simplicity of the technique.4 5 7 One of these5 demonstrated the advantages of a combined intercostal block; the others demonstrated that VAS pain scores and i.v. morphine requirements were less in patients receiving either intrathecal morphine4 or fentanyl.7 Most of the studies concerning the administration of intrathecal opioids in thoracic or cardiac surgery focused on the first 24 post-operative hours and evaluated pain at rest.4 5 7 10 14 15 A decrease in rescue i.v. morphine is reported consistently over this period. Chaney and colleagues, who extended the study period to 48 h, found that morphine consumption was reduced only during the first 24 h.9 In only one study were VAS scores at rest lower over a 30-h period in a treated group that received intrathecal morphine 500 µg.16
Morphine was administered at the lumbar level and might achieve effective analgesic CSF concentrations at the thoracic level only after significant cephalad movement of the lumbar CSF. Thus intrathecal morphine might require several hours to produce adequate pain control. To decrease the delay in the action of morphine, we combined it with sufentanil. Although we did not compare the SM group with a group of patients receiving only morphine, the comparison with the control group demonstrates that the combination of morphine and sufentanil is immediately effective in the post-operative period. Indeed, patients in the treated group required less i.v. morphine in recovery despite the greater dose of i.v. sufentanil administered during surgery. Previous data supporting this finding have shown the superiority of intrathecal over the i.v. and epidural routes of sufentanil administration.17 However, the rapid clearance of sufentanil from the CSF18 does not guarantee analgesia of long duration, which is better ensured by intrathecal morphine.
The duration of action of the combination of intrathecal morphine and sufentanil was, nevertheless, limited to 24 h. A larger dose of morphine may increase duration but would increase the incidence of side-effects, especially respiratory depression.
Pain at rest was well controlled in patients in the group receiving spinal opioids. On the contrary, some patients in this group and most of the patients in the i.v. morphine (control) group experienced severe pain on coughing during the first 24 h. Despite clear recommendations, only a minority of other studies have measured dynamic pain after thoracic surgery. Perttunen and colleagues reported pain intensity on coughing similar to the present results in patients treated by epidural, paravertebral and intercostal nerve blocks,19 and Guinard and colleagues also described high VAS scores on coughing in patients given i.v. or lumbar or thoracic epidural fentanyl.20 From these results, it can be concluded that even analgesic techniques considered as being very effective may fail to give complete pain control after thoracic surgery.
Supplementary i.v. morphine was still required in the SM group, indicating that intrathecal opioid administration did not give complete analgesia. Therefore, we consider intrathecal administration to be the core of a multimodal analgesic approach, including parenteral administration of other analgesic agentsan approach recommended by others.21
Intrathecal morphine and sufentanil did not delay extubation in the present study. This is at variance with studies concerning coronary artery bypass grafting (CABG).8 9 In one study, the authors administered a large dose of morphine (4 mg) but patients received controlled ventilation for more than 12 h.8 In the other study, the same authors reported that intrathecal morphine 10 µg kg1 delayed tracheal extubation significantly.9 This dose was higher than that given in the present study, and the CABG patients also received large i.v. doses of fentanyl during surgery. Shroff and colleagues administered intrathecal morphine 10 µg kg1 combined with intrathecal fentanyl 25 µg, but they gave i.v. opioid on demand, during CABG.10 They demonstrated that extubation occurred earlier in the intrathecal group than in the control group. After intrathecal administration of sufentanil 50 µg and morphine 500 µg, early extubation was also possible6 but, after CABG surgery, whatever the dose of opioid administered, extubation never occurred before several hours of controlled ventilation, making any comparison with thoracic surgery for lung resection rather difficult.
This study confirms the lack of effect of intrathecal opioids on spirometric variables indicative of post-operative pulmonary function, despite better control of post-operative pain.22 Occasionally, others have demonstrated a marginal correction in the post-operative decrease in respiratory performance.7 14 Data from most studies are in agreement with those of the present study, even if it can be demonstrated that effective post-operative analgesia decreases post-operative pulmonary morbidity.22 Urinary retention was the most worrisome complication in our study, confirming the reports of others.23
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References |
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2 Cousins MJ, Mather LE, Glynn CJ, et al. Selective spinal analgesia. Lancet 1979; i: 1141
3 Stoetling RK. Intrathecal morphine: an underused combination for postoperative pain management. Anesth Analg 1989; 68: 7079[ISI][Medline]
4 Neustein SM, Cohen E. Intrathecal morphine during thoracotomy, Part II: Effect on postoperative meperidine requirements and pulmonary function tests. J Cardiovasc Anesth 1993; 7: 1579
5 Liu M, Rock LM, Grass JA, et al. Double-blind randomized evaluation of intercostal nerve blocks as an adjuvant to subarachnoid administered morphine for post-thoracotomy analgesia. Reg Anesth 1995; 20: 41825[ISI][Medline]
6 Swenson JD, Hullander RM, Wingler K, Leivers D. Early extubation after cardiac surgery using combined intrathecal sufentanil and morphine. J Cardiothorac Vasc Anesth 1994; 8: 50914[Medline]
7 Sudarshan G, Browne B, Matthews J, Conacher I. Intrathecal fentanyl for post-thoracotomy pain. Br J Anaesth 1995; 75: 1922
8 Chaney MA, Smith KR, Barclay JC, Slogoff S. Large-dose intrathecal morphine for coronary artery bypass grafting. Anesth Analg 1996; 83: 21522[Abstract]
9 Chaney MA, Furry P, Fluder EM, Slogoff S. Intrathecal morphine for coronary artery bypass grafting and early extubation. Anesth Analg 1997; 84: 2418[Abstract]
10 Shroff A, Rooke GA, Bishop MJ. Effects of intrathecal opioid on extubation time, analgesia, and intensive care unit stay following coronary artery bypass grafting. J Clin Anesth 1997; 9: 4159[ISI][Medline]
11 Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids. Anesthesiology 1984; 61: 276310[ISI][Medline]
12 Sinatra RS, Sevarino FB, Chung JH, et al. Comparison of epidurally administered sufentanil, morphine, and sufentanilmorphine combination for postoperative analgesia. Anesth Analg 1991; 72: 5227[Abstract]
13 Dottrens M, Rifat K, Morel DR. Comparison of extradural administration of sufentanil, morphine and sufentanilmorphine combination after cesarean section. Br J Anaesth 1992; 69: 912[Abstract]
14 Gray JR, Fromme GA, Nauss LA, et al. Intrathecal morphine for postthoracotomy pain. Anesth Analg 1986; 65: 8736[Abstract]
15 Fitzpatrick GJ, Moriarty DC. Intrathecal morphine in the management of pain following cardiac surgery. A comparison with morphine i.v. Br J Anaesth 1988; 60: 63944[Abstract]
16 Vanstrum GS, Bjornson KM, Ilko R. Postoperative effects of intrathecal morphine in coronary artery bypass surgery. Anesth Analg 1988; 67: 2617[Abstract]
17 Camann WR, Denney RA, Holby ED, Datta S. A comparison of intrathecal, epidural, and intravenous sufentanil for labor analgesia. Anesthesiology 1992; 77: 8847[ISI][Medline]
18 Hansdottir V, Hedner T, Woestenborghs R, Norderg G. The CSF and plasma pharmacokinetics of sufentanil after intrathecal administration. Anesthesiology 1991; 74: 2649[ISI][Medline]
19 Perttunen K, Nilsson E, Heinonen J, et al. Extradural, paravertebral and intercostal nerve blocks for post-thoracotomy pain. Br J Anaesth 1995; 75: 5417
20 Guinard JP, Mavrocordatos P, Chiolero R, Carpenter RL. A randomized comparison of intravenous versus lumbar and thoracic epidural fentanyl for analgesia after thoracotomy. Anesthesiology 1992; 77: 110815[ISI][Medline]
21 Kehlet H, Dahl JB. The value of multimodal or balanced analgesia in postoperative pain treatment. Anesth Analg 1993; 77: 104856[ISI][Medline]
22 Ballantyne, JC, Carr DB, deFerranti S, et al. The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anesth Analg 1998; 86: 598612[Abstract]
23 Gentili M, Bonnet F. Spinal clonidine produces less urinary retention than spinal morphine. Br J Anaesth 1996; 76: 8723