Intra-articular morphine for pain relief after knee arthroscopy

BACKGROUND: Peripheral opioid analgesia is well documented. But the clinical usefulness of intra-articular morphine after surgery is uncertain. The aim of the present study was to evaluate the analgesic effects of intra-articular morphine after knee arthroscopy. METHODS: In this parallel-group, double-blind study, 90 patients were randomised to receive either morphine 1 mg, morphine 2 mg or placebo in 5 ml saline intra-articularly at the end of arthroscopic knee surgery. Anaesthetic technique was local infiltration and intra-articular injection of lidocaine. Analgesic efficacy was evaluated by a global pain score, pain intensity (visual analogue scale), and analgesic requirements (paracetamol) during the first 48 h postoperatively. RESULTS: No significant differences between the groups were found for any of the efficacy variables. A majority of the patients had mild pain throughout the study, thus possibly compromising study sensitivity. In a subgroup with more intense pain early after arthroscopy, intra-articular morphine 2 mg reduced pain intensity (P < 0.05) and analgesic requirements (P < 0.05) compared with placebo. CONCLUSION: Postoperative analgesic effect of intra-articular morphine was found only in a subgroup of patients with higher pain intensity in the immediate postanaesthetic period. Possible reasons for our overall negative findings include low study sensitivity due to weak pain stimulus, lack of inflammation that may be a prerequisite for peripheral opioid analgesia, and the local anaesthetic, which impedes local inflammatory reaction and expression of peripheral opioid receptors. These factors may also explain the conflicting results in other studies.     

Intravenous ketoprofen for pain relief after total hip or knee replacement

Background: There are few studies in which ketoprofen, a propionic acid derivate NSAID, has been tested as an intravenous postoperative analgesic. The aim of this double-blind, randomized, placebo-controlled work was to study the tolerability and efficacy of intravenous ketoprofen in seventy-six patients undergoing hip or knee total endoprothesis surgery using three different doses.
Methods: The patients received either ketoprofen 50 mg, 100 mg or 150 mg, or placebo as an initial intravenous loading, followed by an infusion containing 50 mg, 100 mg or 150 mg or placebo, respectively, over the following eleven and a half hours. The consumption of fentanyl was recorded and the patients assessed their pain intensity on a 10-cm visual analogue scale (VAS) at 0, 2, 4 and 12 hours. Possible side-effects were recorded at the same intervals.
Results: Patients receiving ketoprofen showed significantly lower total fentanyl consumption and significantly better pain relief at 12 hours was achieved by a 300 mg dose of ketoprofen than by placebo. Side-effects were minimal, with no differences between the groups.
Conclusion : A bolus of ketoprofen following continuous infusion of ketoprofen, coupled with a PCA-system, was an effective and safe approach for the relief of postoperative pain.     

Controlled comparison of nalbuphine and morphine for post-tonsillectomy pain

A controlled investigation was conducted to compare the effectiveness of morphine and nalbuphine in the prevention of pain and restlessness after tonsillectomy in children. Sixty children between 4 and 12 years old were randomly allocated to receive intramuscular morphine 0.2 mg/kg, nalbuphine 0.3 mg/kg or no medication approximately 5 minutes before the conclusion of surgery. Pain and restlessness were assessed 1 and 2 hours after injection, and side effects were recorded. The assessments were made double-blind. Both nalbuphine and morphine decreased restlessness and pain 1 hour (p less than 0.01) and 2 hours (p less than 0.05) after surgery. No significant differences were found between the two groups of patients who received opioids. Both nalbuphine and morphine caused more drowsiness than placebo 2 hours after surgery (p less than 0.001). Other side effects were uncommon. Nalbuphine may offer advantages compared with morphine in regard to safety and convenience of use for the treatment of post-tonsillectomy pain in children.     

Epidural versus intrathecal morphine for postoperative analgesia after Caesarean section

Background. Perispinal anaesthesia for Caesarean section allowsinjection of epidural (ED) or intrathecal (i.t.) morphine toprovide long-lasting postoperative analgesia. To compare thesetwo routes, a prospective, randomized, double-blinded studyof 53 patients undergoing elective Caesarean section was performed. Methods. Combined spinal-epidural anaesthesia with 6 mg of i.t.hyperbaric bupivacaine plus sufentanil 5 µg, and additionalED lidocaine was used. Additionally, each patient received either2 mg (2 ml) of ED morphine plus 1 ml of i.t. normal saline (EDgroup, n=28), or 0.075 mg (1 ml) of i.t. morphine plus 2 mlof ED normal saline (i.t. group, n=25). Additional postoperativeanalgesia was given in the form of propacetamol and ketoprofen,plus self-administered i.v. morphine. Results. No major respiratory depression occurred. Time to firstdemand of morphine was similar in the ED (307.5 min) and i.t.(310 min) groups, as was the incidence of side-effects suchas sedation, pruritis, nausea, and vomiting. During the first24 postoperative hours, VAS pain scores were greater in thei.t. group (P=0.032), as was additional morphine consumption(4 vs 1.5 mg) (P=0.03). Conclusions. The ED protocol was more effective than the i.t.protocol, whilst side-effects were similar. Br J Anaesth 2003; 91: 690–4     

Intrathecal sufentanil and morphine for post-thoracotomy pain relief

In this double-blind randomized study we compared a group of15 patients undergoing thoracotomy who received a spinal injectionof sufentanil 20 µg combined with morphine (200 µg)after induction of general anaesthesia with a control groupof the same size. Post-operative pain was rated on a visualanalogue scale (VAS) and a verbal rating scale at rest and witha VAS on coughing. In the recovery room, patients received titratedi.v. morphine until the VAS score was <30, and were followedby patient-controlled analgesia (PCA) for 72 h. The intrathecalsufentanil and morphine group had a lower intra-operative requirementfor i.v. sufentanil and needed less i.v. morphine for titrationin the recovery room. I.v. PCA morphine consumption and painscores were lower in the active group than in the control groupduring the first 24 h. There were no differences afterthis time. Spirometric data (peak expiratory flow, forced vitalcapacity and forced expiratory volume in 1 s) were similarin the two groups. We conclude that the combination of intrathecalsufentanil and morphine produces analgesia of rapid onset andwith a duration of 24 h. Br J Anaesth 2001; 86: 236–40.     

Comparison between patient-controlled analgesia and subcutaneous morphine in elderly patients after total hip replacement

Background. The goal of this study was to evaluate the effectivenesson postoperative pain, and cognitive impact, of patient-controlledanalgesia (PCA) compared with subcutaneous (s.c.) injectionsof morphine in elderly patients undergoing total hip replacement(THR). Methods. Forty patients older than 70 yr were randomly assignedto two different postoperative analgesic techniques for 48 h:i.v. PCA morphine (dose, 1 mg; lockout interval, 8 min; PCAgroup) or regular s.c. morphine injections (SC group). Postoperativepain was assessed at rest and when moving, using a visual analoguescale (VAS) every 4 h. A Mini Mental Status (MMS) examinationwas used to assess cognitive functions before surgery, at 2h, 24 h and 48 h after surgery, and at hospital discharge. Side-effectswere also recorded systematically during the first 48 h aftersurgery. Results. The PCA group showed significantly lower pain scoresthan the SC group both at rest and during mobilization. However,the clinical significance of pain scores was weak. There wasno intergroup difference in postoperative MMS scores. The incidenceof side-effects was similar in both groups. Conclusions. We conclude that in healthy elderly subjects undergoingTHR, the flexibility of the analgesic regimen is more importantthan the route of administration with regard to efficacy, adverseeffects and recovery of cognitive function. Br J Anaesth 2003; 90: 53–7     

Use of intrathecal morphine for postoperative pain relief after elective laparoscopic colorectal surgery

Laparoscopic surgery has become popular in recent years, but few studies have addressed analgesia for this type of surgery. We conducted a prospective double-blind randomised trial on 36 cases of laparoscopic colorectal surgery to determine the influence of intrathecal morphine on postoperative pain relief. All patients received a subarachnoid block with local anaesthetic in addition to general anaesthesia. One group also received intrathecal morphine. A patient-controlled analgesic (PCA) device was prescribed for pain control postoperatively and the visual analogue score (VAS) was used for pain assessment. The group who received intrathecal morphine used significantly less morphine. There were no adverse cardiovascular effects of the combined anaesthetic technique. Nausea and vomiting remained the main side-effect of intrathecal morphine but this was easily treated with anti-emetics.     

Intrathecal morphine (ITM) for postoperative pain control in children: a comparison with nalbuphine patient controlled analgesia (PCA)

This is a retrospective study covering the ten-year period 1984–1993. Single shot spinal morphine (ITM) is compared with PCA nalbuphine for postoperative pain relief in children having abdominal or thoracic procedures. The records of 52 patients meeting selection criteria were examined. Nursing and physician notations were reviewed for hourly pain assessments, evidence of associated complications, respiratory depression, nausea and or vomiting, pruritus, and urinary retention. ITM provided significantly better pain relief (2.2 h in pain) during the first 24 h postoperatively than PCA nalbuphine (9.2 h in pain). With the exception of urinary retention which was significantly more frequent following ITM (58.6%) compared to PCA nalbuphine (8.7%), narcotic related complications were not different between the two groups. No difference in duration of hospital stay or ICU stay could be demonstrated. We conclude that ITM provides better pain relief, without more serious complications, than PCA nalbuphine. We recommend it as a safe, effective technique to treat postoperative pain in children following thoracic or upper abdominal procedures.     

Self-administered nalbuphine, morphine and pethidine

In a double-blind clinical trial of 48 patients, nalbuphine, morphine, and pethidine were compared by on-demand intravenous analgesia during the first 24 hours after cholecystectomy. Overall pain relief (visual analogue score) was recorded by the patients as 50 (SEM 4) for nalbuphine, 44 (SEM 4) for morphine and 53 (SEM 5) for pethidine. These scores were not significantly different. The mean demand for each drug over the 24-hour period was 70 (SEM 12) mg for nalbuphine, 46 (SEM 6) mg for morphine and 614 (SEM 49) mg for pethidine. Pain on movement, either during deep breathing or turning, was found to be less well controlled after nalbuphine (70, SEM 2), and pethidine (67 SEM 7) than after morphine (52, SEM 5; p less than 0.01). The incidence of side effects was similar with each drug. Nalbuphine is a useful postoperative analgesic, as effective as pethidine. Nalbuphine 15 mg is apparently equipotent with morphine 10 mg or pethidine 120 mg by this mode of administration.     

Intravenous versus intraperitoneal morphine before surgery to provide postoperative pain relief

Background: Opioid receptors have been demonstrated on peripheral afferent nerves throughout the body. The aim of the present study was to compare the effects of intravenous and intraperitoneal administration of morphine with regard to pain, postoperative morphinerequirement, and recovery after major abdominal surgery, and to describe the pharmacokinetics of intraperitoneal morphine in humans.
Methods: In a double-blind manner, 30 patientsscheduled for major abdominal surgery were randomized to either 50 mg of morphine intravenously (IV) or 50 mg of morphine intraperitoneally (IP) before operation. Pain was measured on a visual analogue scale and morphine requirements were registered for 3 days. Recovery was measured as time to oral intake of food, time to flatulence and days in hospital. Plasma morphine, mor-phine-3-glucuronide, and morphine-6-glucuronide concentrations were determined during the first 4 h after morphine administration.
Results: During the first postoperative hours there was less pain at rest ( P =0.02) and on coughing ( P =0.004) in the intravenous group. The requirementof additional morphine ( P =0.016) was lower in the intravenous group during the first postoperative day. No major differences in recovery were seen. The plasma concentrations of morphine measured as area under the curve (AUC) during the first 4 h were similar, but the intravenous group showed significantly higher concentrations of the active metabolite morphine-6-glucuronide, (P=0.016), indicating a difference in pharmacokinetics after intraperitoneal compared to intravenous administration of morphine.
Conclusion: Intraperitoneal administration of 50 mg of morphine before major abdominal surgery is less efficient in reducing pain and postoperative morphine requirements than thesame amount of morphine given intravenously.     

Epidural morphine for postoperative pain relief in children

Epidural morphine for postoperative pain relief is in general use, and has proved to be very efficient in adults. The epidural technique and the use of epidural morphine are much less frequent in children. For 2 years we have prospectively followed 76 children who had epidural morphine for postoperative pain relief after major abdominal surgery. The age distribution was from newborn to 13 years, with a median age of 12 months. It was estimated that 94% of the patients had good analgesia for the first 24 postoperative hours and no other opioids were given. The side effects were few, but one case of respiratory depression was seen and 20% of the children had pruritus. There were four dural punctures and three catheters slipped out accidentally, but otherwise the treatment was continued as long as it was considered necessary (1–11 days). The use of postoperative ventilatory support decreased during the investigation. We observed a change in the sleeping pattern with an increased number of sleep–induced myoclonia during the administration of epidural morphine. In conclusion, the use of epidural morphine in children for postoperative pain relief is very efficient. The minimal effective dose has not been established as yet, but 50 Hg/kg every 8 h, supplemented with small doses of bupivacaine, provides excellent analgesia in the immediate postoperative period after major abdominal surgery. The side effects are few, but the risk of respiratory depression is always present and observation in the intensive care unit or recovery for the first 24 h is strongly recommended.     

A comparison of nalbuphine and morphine as premedication agents for minor gynaecological surgery

Nalbuphine 10 mg and morphine 10 mg were compared in a randomised double-blind trial as intramuscular premedication in 50 patients undergoing minor gynaecological surgery. Both nalbuphine and morphine produced significant sedation without anxiolysis as assessed by patient linear analogue scales, but there were no significant differences between the two drugs. Observer ratings demonstrated that nalbuphine produced calm/sleepy patients to a greater extent than morphine. There were no differences in untoward effects produced by each drug.     

Continuous epidural analgesia with bupivacaine-fentanyl versus patient-controlled analgesia with i.v. morphine for postoperative pain relief after knee ligament surgery

BACKGROUND: Both epidural analgesia and intravenous patient-controlled analgesia (PCA) have been found efficacious after various types of surgery. We compared the efficacy, safety, side effects and patient satisfaction of these methods in a randomized double-blind fashion after elective anterior cruciate ligament reconstruction of the knee. METHODS: Fifty-six patients had an epidural catheter placed at the L2-L3 interspace. Spinal anaesthesia with 15 mg of plain bupivacaine 5 mg/ml was performed at the L3-L4 interspace. After surgery the patients were randomly divided into three groups: 19 received a continuous epidural infusion with bupivacaine 1 mg/ml and fentanyl 10 mg/ml (F10), 19 patients received bupivacaine 1 mg/ml and fentanyl 5 microg/ml (F5) and 18 patients received saline (S). The rate of the epidural infusions was 0.1 ml kg(-1) h(-1). Each patient could also use an intravenous (i.v.) PCA device with 40 microg/kg bolus doses of morphine with a lockout period of 10 min and a maximum dose 240 microg kg(-1) h(-1). At the end of surgery ketoprofen 100 mg i.v. was given and continued orally three times a day. Patients were assessed for pain with a visual analogue scale (VAS) at rest and during activity, side effects and satisfaction at 3, 9 and 20 h. RESULTS: Both epidural infusions (F10, F5) provided better analgesia than epidural saline plus i.v. PCA (S) (P<0.05). There was slightly less nausea in the S group (NS). In spite of the difference in the quality of pain relief, there was no difference between the groups in patient satisfaction regarding analgesic therapy. CONCLUSION: Epidural infusion of fentanyl (1 microg kg(-1) h(-1) or 0.5 microg kg(-1) h(-1)) and bupivacaine (0.1 mg kg(-1) h(-1)) provided better pain relief but more side effects than intravenous morphine patient-controlled analgesia after knee ligament surgery. Almost all patients in all groups were satisfied with their pain relief.     

Continuous subcutaneous infusion of morphine for postoperative pain relief

A double-blind randomised study of 48 patients in whom continuous subcutaneous infusion and regular intramuscular injection of morphine were compared as analgesic regimens after upper abdominal surgery, is described. Over a 48-hour period, no difference in pain intensity between the two groups was found by comparing linear analogue scores, assessments on a four-point rank scale, peak expiratory flow rates or requirement for additional analgesia. Nausea and sedation were assessed using a four-point rank scale. These side effects were less frequent with subcutaneous infusion (p less than 0.05). Two patients from each group were judged to have received an overdose. The infusion apparatus was simple and convenient to use. Continuous subcutaneous infusion of morphine is a practical and effective means of achieving post-operative analgesia but, as with other mandatory dosing regimens, relative overdosage may occur.     

Iontophoretic transdermal system using fentanyl compared with patient-controlled intravenous analgesia using morphine for postoperative pain management

Background: The fentanyl iontophoretic transdermal system (fentanyl ITS)enables needle-free, patient-controlled analgesia for postoperativepain management. This study compared the efficacy, safety, andease of care of fentanyl ITS with patient-controlled, i.v. analgesia(PCIA) with morphine for postoperative pain management. Methods: A prospective, randomized, multicentre trial enrolled patientsin Europe after abdominal or orthopaedic surgery. Patients receivedfentanyl ITS (n = 325; 40.0 µg fentanyl over 10 min) ormorphine PCIA [n = 335; bolus doses (standard at each hospital)]for 72 h. Supplemental i.v. morphine was available during thefirst 3 h. The primary efficacy measure was the patient globalassessment (PGA) of the pain control method during the first24 h. Results: PGA ratings of ‘good’ or ‘excellent’were reported by 86.2 and 87.5% of patients using fentanyl ITSor morphine PCIA, respectively (95% CI, –6.5 to 3.9%).Mean (SD) last pain intensity scores (numerical rating scale,0–10) were 1.8 (1.77) and 1.9 (1.86) in the fentanyl ITSand morphine PCIA groups, respectively (95% CI, –0.38to 0.18). More patients reported a system-related problem forfentanyl ITS than morphine PCIA (51.1 vs 17.9%, respectively).However, fewer of these problems interrupted pain control (4.4vs 41.3%, respectively). Patients, nurses, and physiotherapistsreported more favourable overall ease-of-care ratings for fentanylITS than morphine PCIA. Study termination rates and opioid-relatedside-effects were similar between groups. Conclusion: Fentanyl ITS and morphine PCIA were comparably effective andsafe.     

Intramuscular ketorolac following total hip replacement with spinal anaesthesia and intrathecal morphine

We have studied the analgesic and morphine sparing effect of ketorolac tromethamine in 60 patients after total hip replacement under spinal anaesthesia.
In this double blind study 30 patients received ketorolac 30 mg IM 6 hourly postoperatively and the control group received saline. Analgesia was assessed by visual analogue pain scores (VAS) and morphine consumption by patient controlled analgesia (PCA). There was a significantly ( P <0.02) lower morphine consumption in the ketorolac group (7.1 ±8.6 mg; Mean±s.d.) when compared to the saline group (14.2±13.6 mg). Although there was a trend for lower VAS on the first postoperative night this was only significant at 10 hours postoperatively and the next morning at 08:00 hr. The incidence of side effects (emetic sequelae, pruritus and headache) were similar in both groups. It is concluded that ketorolac reduces the consumption of additional morphine in conjunction with intrathecal morphine but had no effects on the side effects.     

Dextromethorphan and intrathecal morphine for analgesia after Caesarean section under spinal anaesthesia

Background. Dextromethorphan is an N-methyl-D-aspartic acidantagonist which can attenuate acute pain with few side-effects.In this prospective, randomized, double-blind study of dextromethorphanand intrathecal morphine, we investigated postoperative pain,pruritus, nausea and vomiting in women undergoing Caesareansection under spinal anaesthesia. Methods. Women were allocated randomly to one of six groups,to receive intrathecal morphine 0.05, 0.1 or 0.2 mg plusoral dextromethorphan 60 mg or placebo. Results. The addition of dextromethorphan did not reduce postoperativepain scores (P=0.83). Compared with women receiving intrathecalmorphine 0.05 mg, women receiving higher doses had a significantlyhigher incidence of nausea and vomiting [odds ratio for intrathecalmorphine 0.1 mg, 4.0 (95% confidence interval 1.2–14.1);for intrathecal morphine 0.2 mg, 7.9 (2.3–27.1)].Compared with women receiving intrathecal morphine 0.05 mg,women receiving higher doses also had a significantly higherincidence of pruritus [odds ratio for intrathecal morphine 0.1 mg,3.2 (95% confidence interval 1.3–8.2); for intrathecalmorphine 0.2 mg, 3.7 (1.4–9.5)]. Women receivingdextromethorphan had a lower incidence of nausea and vomiting[odds ratio 2.6 (1.1–6.3)]. Conclusions. Postoperative pain after Caesarean section underspinal anaesthesia was not reduced by the addition of oral dextromethorphanto a multimodal approach including intrathecal morphine. Br J Anaesth 2003; 90: 653–8     

Gastric emptying and small bowel transit times in volunteers after intravenous morphine and nalbuphine

Gastric emptying half-times and small intestinal transit times were measured in a double-blind crossover study of 17 volunteers who received an intravenous injection of nalbuphine (5 or 10 mg), morphine (5 mg) or placebo. Both times were monitored using a gamma camera after a radioactive test meal and gastric emptying half-time was calculated. Small intestinal transit time was measured by the appearance of radioactivity in the caecum and also of hydrogen in end tidal air. Gastric emptying was prolonged over placebo by nalbuphine 10 mg, which had more effect than nalbuphine 5 mg or morphine 5 mg; morphine 5 mg had less effect than nalbuphine 5 mg. Small intestinal transit time was prolonged over placebo by nalbuphine 10 mg more than by nalbuphine 5 mg or morphine 5 mg, which had approximately equal effects. In these respects, the potency ratio of nalbuphine appears roughly equivalent to morphine. Small intestinal transit times measured by end tidal hydrogen concentration and gamma camera showed close agreement.     

A comparison of nalbuphine with fentanyl for postoperative pain relief following termination of pregnancy under day care anaesthesia

A double-blind investigation was undertaken to compare the efficacy of nalbuphine and fentanyl in the prevention of pain after day case termination of pregnancy. Forty patients were allocated randomly to receive nalbuphine 0.25 mg/kg or fentanyl 1.5 micrograms/kg immediately before induction of anaesthesia. The patients completed scores for pain and nausea, and performed a reaction time test to assess recovery. An observer assessed patient appearance at 1, 2 and 4 hours postoperatively. Patients who received nalbuphine had significantly lower pain scores at 1 hour (p less than 0.01) and 2 hours (p less than 0.05) and required significantly (p less than 0.05) less postoperative analgesia. No significant differences were found between the groups for incidence of nausea or for observer assessment of appearance. There was some evidence of psychomotor impairment at 2 hours in the nalbuphine group. Freedom from Controlled Drug Act regulations and improved analgesia with nalbuphine, render it more satisfactory for day case surgery than the more commonly used fentanyl.     

Intravenous regional analgesia using morphine. The effect on postoperative pain following total knee arthroplasty

Background: We hypothesised that any peripheral action of morphine may contibute to improved postoperative analgesia. The aim of this study was to evaluate the analgesic efficacy of morphine administered preoperatively into an exsanguinated limb prior to total knee arthroplasty.
Methods: A randomised, double-blind, controlled study was performed in 50 patients having total knee arthroplasty surgery. Patients were divided into two groups. In the study group, 0.125 mg/kg morphine in 60 ml of saline was administered intravenously (iv) into the exsanguinated operative limb via a can-nula in the foot. A saline intramuscular (im) injection was administered into the opposite leg. The control group received 60 ml saline iv into the operative leg and 0.12 5mg/kg morphine im into the opposite leg. Pain was assessed postoperatively using a 10-point visual analogue scale and by comparing morphine requirements and demand: delivery ratios from a patient-controlled analgesic pump.
Results: We found no statistically significant difference between the groups in relation to any of the analgesic measures employed.
Conclusions: Intravenous regional analgesia using morphine provides no analgesic advantage over the intramuscular route from 6–24 h postoperatively.