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A Comparison of Regularly Administered Sustained Release Oral Morphine with Intramuscular Morphine for Control of Postoperative Pain

Bourke, Margaret FFARCSI; Hayes, Agnes FFARCSI; Doyle, Maire FFARCSI; McCarroll, Maire FFARCSI

doi: 10.1213/00000539-200002000-00034

We studied the efficacy and side effect profile of regularly administered, oral sustained-release morphine sulfate tablets (MST) and IM morphine in patients undergoing total hip arthroplasty under lumbar spinal anesthesia. Patients in Group I received MST 20 mg 12 hourly and a placebo IM injection 6 hourly regularly. Group II patients received an oral placebo 12 hourly and morphine sulfate 10 mg IM 6 hourly regularly. Rescue analgesia was provided with regular diclofenac suppositories and patient-controlled analgesia. Pain scores assessed by using visual analog scale and verbal pain scoring at rest and with movement were low in both groups, with no statistical difference between groups. Mean patient-controlled analgesia morphine consumption during the 48-h study was 16.7 mg in the IM group and 25.9 mg in the MST group. The difference between the groups was significant at 36 h postoperatively (0.03). Side effects of sedation and respiratory depression were not problematic in either group, with a maximal sedation score of 2 occurring once in a patient in Group II. Nausea and vomiting occurred more often in Group II, but this was not statistically significant, with a mean nausea/vomiting score for Group II of 1.7. We conclude that oral, sustained-release morphine is an attractive alternative to IM opiates in patients undergoing body surface surgery under regional anesthesia.

Implications Each postoperative analgesic has its own limitations for route of administration, dosage, and potential side effects. Using the oral route for drug administration seems more attractive than other methods but may not be suitable in all postoperative patients. We studied the efficacy and side effect profile of sustained-release, oral morphine compared with standard IM morphine for the treatment of pain after hip replacement surgery. We concluded that use of the oral preparation is a suitable alternative to the IM route in this population undergoing surgery under spinal anesthesia.

Department of Anesthesia, Cappagh Orthopaedic Hospital, Dublin, Ireland

October 27, 1999.

This study was supported in part by the Cappagh Hospital Trust.

Address correspondence and reprint requests to Dr. M. McCarroll, Department of Anesthesia, Cappagh Orthopaedic Hospital, Dublin 11, Ireland.

Despite the availability of effective opioid analgesic drugs, treatment of postsurgical pain is still often inadequate (1–3). One reason for this is the use of IM “on demand” opiates, yet this is still one of the most commonly prescribed regimens for postoperative pain relief (4–7). Sophisticated analgesia techniques, such as epidural and patient-controlled analgesia (PCA), are neither necessary nor realistic for most patients. Analgesia equal to that provided by IM morphine can be obtained by using morphine sulfate slow-release tablets (MST) (8). Concerns regarding “dumping” (the sudden absorption of drug into the circulation after the resolution of ileus) and increased sedation have tempered enthusiasm for the use of oral, sustained-release opioids in the control of postoperative pain (9).

Patients presenting for total hip arthroplasty (THA) are a homogenous population with relatively standard analgesic requirements. The practice in our institution is to perform this operation under spinal anesthesia. Postoperative analgesia is provided with a combination of diclofenac sodium suppositories and IM morphine sulfate on a pro re nata basis. Because spinal anesthesia causes minimal disruption of the gastrointestinal tract, patients can take free fluids after returning to the ward. The possibility of providing postoperative analgesia with oral preparations in this patient population seems attractive. Use of a sustained release oral opiate may avoid some of the commonly cited limitations of the IM route, i.e., painful injections, avoiding the use of needles, peaks and troughs of drug effect, and consequently adverse effects.

This study was designed to compare the analgesic efficacy and incidence of side effects of regularly administered MST with our current practice of IM morphine.

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National Drugs Advisory Board and Ethical Committee approvals were obtained. After informed consent, 40 patients, ASA physical status I and II, scheduled to undergo elective primary THA under spinal anesthesia, were randomly allocated to one of two treatment groups. Exclusion criteria included known sensitivity to morphine or diclofenac, renal impairment, peptic ulcer disease, rheumatoid arthritis, use of opioids before admission, and inability to use PCA.

All patients were premedicated with diazepam 10 mg orally 90 min before spinal anesthesia with bupivacaine 0.5% 3 mL. The height of the block achieved was documented. No opioids were administered intraoperatively. The use of IV diazepam was permitted intraoperatively for sedation, at the discretion of the attending anesthesiologist and its use and dosage were documented. Diclofenac sodium 100 mg was administered rectally after spinal anesthesia and at 16-h intervals for the duration of the study.

Patients in Group I (n = 19) received MST 20 mg orally with their premedication and every 12 h thereafter for 48 h. In addition, patients in Group I received a 1-mL placebo IM injection 6 hourly for 48 h, after regression of spinal motor block. Patients in Group II (n = 20) received a placebo tablet with their premedication and every 12 h thereafter for the study period and morphine 10 mg, IM was administered after regression of spinal motor block and 6 hourly thereafter for 48 h. Patients were blinded as to which form of analgesia they were receiving.

Rescue analgesia was provided for all patients in the form of PCA morphine with droperidol, 120 mg and 10 mg in 60 mL, respectively, with bolus doses of 1 mg of morphine, a lockout time of 5 min and a 4-hourly limit of 20 mg. No alterations in the fixed dose of oral or IM morphine were permitted.

Nausea and/or vomiting was treated with cyclizine 0.7 mg/kg IM 6 hourly at the discretion of the attending nurse. Rescue antiemetic was at the discretion of the attending physician.

Patients remained in the recovery area until regression of motor block, at which time the first set of assessments was performed, followed by administration of the first IM injection. Subsequent assessments were made every 6 hours, before drug administration, for the 48-h study period. Assessment of pain intensity included verbal pain score at rest and with movement and the visual analog scale, on which the zero point represented “no pain” and 10, the “worst pain imaginable.” A verbal pain score was evaluated on a four-point scale, on which 0 = no pain, 1 = mild pain, 2 = moderate pain, and 3 = severe pain. The amount of PCA used by the patient in the preceding 6 h was recorded. The level of sedation was recorded as 0 = awake, 1 = asleep but easily arousable, 2 = asleep and difficult to arouse, 3 = unarousable. Episodes of nausea and vomiting were graded on a scale of 0 to 3, on which 0 = no episodes of nausea or vomiting, 1 = nausea, 2 = nausea with two or fewer episodes of vomiting, and 3 = nausea and more than two episodes of emesis. The use of antiemetics was documented. Patients who were severely nauseated or unable to tolerate oral fluids in the postoperative period were withdrawn from further participation in the study. Regular administration of analgesia could be halved or omitted by the nursing staff if the patient had a sedation score of more than 2 or if the patient had respiratory depression, taken as a respiratory rate <10 breaths/min.

Data were analyzed for statistical significance by using χ2 test with Yates’ correction for nominal data, two sample t-test for parametric data, and Mann-Whitney U-test for nonparametric data. A P value of < 0.05 was taken to be statistically significant.

Power analysis confirmed that sample size was adequate to prevent a Type II error.

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Nineteen patients were enrolled in Group I and 20 patients in Group II. Mean patient age was 66.15 yr in Group I and 67.25 yr in Group II. The groups were comparable in terms of age, weight, and sex. There was no statistically significant difference between groups with respect to the volume of local anesthetic administered or the height of the sensory block achieved.

Ten patients in Group II and four patients in Group I received sedation intraoperatively. Patients in Group II received larger doses of diazepam intraoperatively than those in Group I; however, this difference did not reach statistical significance.

Only one patient complained of severe pain at one assessment time; this occurred at 0 h in Group I. Typical verbal pain scores were 0 or 1. Mean visual analog scale pain scores were <1.5 in both groups at all times. There was no statistical difference in pain scores between groups. Mean morphine consumption via PCA over the 48-h period was 16.7 mg in the IM morphine group and 25.9 mg in the MST group. However, only the difference in PCA morphine usage at 36 h reached statistical significance (P = 0.03) (Figure 1). The time to peak use of PCA was at 6 h postregression of motor block in both groups.

Figure 1

Figure 1

The incidence of sedation was infrequent in both groups with one patient in Group II having a sedation score of 2 at 24 h. No patient experienced respiratory depression.

Although nausea and/or vomiting and the use of antiemetics occurred more commonly in the IM morphine group, this was not statistically significant (P = 0.25 and P = 0.09 respectively). The mean nausea/vomiting score for the patients in Group I was 0.55 and for those in Group II was 1.2, with no patient experiencing more than two episodes of emesis. Among patients in Group I, there were a total of 10 episodes of nausea or vomiting which were experienced by five patients. In Group II, 23 episodes of nausea or vomiting were experienced among 10 patients. One patient in Group I and nine patients in Group II received antiemetics per study protocol. One patient in Group II required the use of a rescue antiemetic.

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Optimal analgesia without the complications of therapy may be particularly difficult to achieve in the elderly, who frequently try to “tough it out,” and may not display typical pain behavior (10). Regularly dosed oral morphine has gained acceptance as the treatment of choice for patients with chronic cancer pain but is rarely used to treat acute postoperative pain. Brahams (11), cautioned against the perioperative use of oral morphine because of fears of delayed absorption in the presence of decreased gastric emptying, produced by pharmacological, physiological, or pathological causes. There have been problems with oral analgesia for patients undergoing surgery with general anesthesia in whom there is interference with gastrointestinal activity and variable absorption (12). The patients in our study, undergoing body surface surgery under spinal anesthesia, were in a subgroup of patients with low risk of gastric stasis and who normally tolerate oral fluids within hours of surgery.

Another area of concern regarding the use of oral opiates after surgery is that nausea and vomiting will preclude or reduce their effectiveness. Indeed McEvoy et al. (13) found a more frequent incidence of nausea in a group of patients taking MST than in a group taking oral diclofenac for postoperative pain. However, in our study the incidence of nausea and vomiting was more frequent in Group II. This probably reflected the peak effect of the IM technique of drug administration. The PCA use and, thus, the dose of droperidol administered were very low in both groups, and probably did not affect the occurrence of nausea and vomiting. None of the patients were withdrawn from the study because of nausea or intolerance of fluids.

Slow release oral morphine has many potential advantages over other methods of postsurgical pain treatment. It is easy to administer, provides more sustained analgesia, has high patient and nursing staff acceptance, and is inexpensive. The total cost of administering regularly dosed sustained release oral morphine for this study patient population was £1.38 (US $1.80) per patient. It produces a quality of analgesia equal to that of regularly administered IM morphine with no greater incidence of the side effects of sedation, respiratory depression, nausea, or vomiting. Although regularly administered analgesia provides superior pain relief than that given pro re nata, there is a reluctance to give regular IM injections, particularly when the patient is not complaining of pain (14). MST may be a useful drug in pain control in patients who have undergone body surface surgery, surgery under regional anesthesia, or others in whom there is little or no disruption of the gastrointestinal tract.

The preemptive use of morphine in combination with spinal anesthesia may account for the low pain scores witnessed in both groups of patients. Using a multimodal approach to analgesia, we can optimize the use and combinations of the drugs and techniques already available to us to ensure a pain-free postoperative period, while minimizing side effects. A combination of regular enteral opioid analgesic, nonsteroidal antiinflammatory drugs, and spinal local anesthetic seems to be a balanced technique for providing postoperative analgesia in this patient population. Furthermore this method has high patient acceptability and lower nurse dependency.

Because pain scores were low in all patients, it is likely that mobilization and time to discharge were similar in both groups, although unfortunately this was not formally assessed.

We conducted a pilot study in order to establish the dosage of morphine for our trial. The dose of IM morphine was chosen based on the average opioid requirement in this patient population in our institution. The dose of MST was selected based on a study by McCormack et al. (14). Because the control of pain is comparable using 8- or 12 hourly dosing regimens of MST (15), we decided on the doses of MST 20 mg 12 hourly and morphine 10 mg IM 6 hourly. The quantity of PCA consumed as rescue analgesia indicates that we could have chosen a larger dose of morphine for regular dosage, particularly in the first 12 hours. MST 30 mg 12 hourly may be a more appropriate dosing regime, with modifications according to individual patient requirements.

In our study, diclofenac was administered rectally, as this was our standard practice. Oral diclofenac is as effective and has the same adverse effects as when administered rectally, and we concur with Moore and McQuay (16) who advocate that “If the patient can swallow, give the drug by mouth!”

We conclude that there is a role for MST in the treatment of elderly patients undergoing THA under spinal anesthesia. We found that regularly administered MST produced analgesia equal to that of regularly administered IM morphine with no increase in side effects. The advantages of the use of oral MST perioperatively are its good baseline analgesia that is established before regression of the subarachnoid block, its low cost, and reduced requirement for nursing intervention.

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