Morphine For Postoperative Pain Relief Research Articles

A Randomized Control Study to Assess the Efficacy of Intrathecal Morphine in Patients on Patient-Controlled Analgesia Pump With Morphine for Postoperative Pain Relief After Elective Laparotomy.

Introduction Laparotomy is associated with significantprolonged postoperative pain, which can cause an adverse neuroendocrine stress response. Intrathecal morphine (ITM) retains an important place in pain management after major laparotomysince it is easier to administer and has a relatively lesser possibility of failure and technical difficulty. Aim The study aims to compare the effect of the administration of ITM with intravenous (IV) morphine administered by a patient-controlled analgesia (PCA) pump on postoperative analgesia after elective laparotomy. The primary objective was to compare total morphine consumption while secondary objectives were to compare pain assessed by the visual analog scale (VAS) and adverse reactions to opioids. Methods Sixty patients who underwent elective laparotomy were enrolled in this study. Thirty patients were enrolled in the study group (ITM+PCA) where ITM (200 mcg) was administered before laparotomy and intravenous morphine was initiated with PCA postoperatively. In the control group, only intravenous morphine was given with PCA postoperatively for pain relief. Parameters in both groups were compared, where estimation of cumulative morphine dose was the primary outcomeand pain as assessed by VASand side effects of opioids were the secondary outcomes. Results Patients in the ITM (ITM+PCA) group required less morphine (6.6 ± 2.96 vs. 24.77 ± 6.79 mg of morphine, p < 0.001) compared to patients on PCA. There was no statistically significant difference in VAS score and adverse effects between both groups. Conclusion Preoperative ITM can be used as an effective and safe modality for alleviating immediate postoperative pain following laparotomy.

Effect of cultural background and healthcare environment on postoperative opioid requirement.

The objective of this prospective observational study was to investigate the interactions between cultural background, healthcare environment, and postoperative pain experience. We enrolled 128 Chinese patients living in rural mainland China and 134 patients in Hong Kong with a higher level of Western cultural influences (defined by educational attainment, place of residence, and ability to understand English). All patients had major abdominal surgery and received patient-controlled analgesia with intravenous morphine for postoperative pain relief. The primary endpoint was total opioid requirement up to 48 hr after surgery. Other measures included pain intensity, opioid-related side effects, and genetic markers for opioid responsiveness. The mean (95% confidence interval) cumulative opioid requirement, expressed as morphine equivalent, during the first 48 hr after surgery was significantly less in patients from mainland China (18.8 [15.7 to 22] mg) compared with patients from Hong Kong (42.0 [38.3 to 45.6] mg, P < 0.0001). In a multivariable analysis, opioid requirement was influenced by ethnicity, duration of surgery, and severity of pain upon admission to the postanesthetic care unit. These results suggest that postoperative pain behaviours and opioid requirement may be influenced by cultural background and healthcare environment in two populations of Chinese descent. Australian and New Zealand Clinical Trials Registry (ACTRN12614000601639); registered 6 May, 2014.

Midazolam as an antiemetic in patients receiving epidural morphine for postoperative pain relief

Epidural morphine has been associated with a significant incidence of postoperative nausea and vomiting (PONV). The authors have evaluated the prophylactic effects of midazolam in preventing nausea and vomiting following epidural morphine for postoperative pain control. The authors studied 80 women (n = 40 in each group) undergoing total abdominal hysterectomy under epidural anesthesia, in a randomized, double-blind, placebo-controlled study. At the end of the surgery, all patients received epidural morphine 3 mg for postoperative pain. Before morphine injection, the midazolam group received low-dose midazolam infusion (1 mg bolus followed by 1 mg h(-1)), while the placebo group received i.v. saline. Patients in the midazolam group reported a lower incidence of total PONV, and a lower frequency of rescue antiemetic request than those in the placebo group (p < 0.05). In addition, midazolam was associated with a reduced incidence of pruritus following epidural morphine (p < 0.05). The authors conclude that low-dose midazolam infusion is effective in the prevention of nausea, vomiting, and pruritus following epidural morphine for postoperative pain control.

Ultra-low-dose Naloxone as an Adjuvant to Patient Controlled Analgesia (PCA) With Morphine for Postoperative Pain Relief Following Lumber Discectomy: A Double-blind, Randomized, Placebo-controlled Trial.

Lumbar discectomy is one of the most commonly performed neurosurgical procedures. Many patients experience postoperative pain after lumbar discectomy. This study evaluated the effect of ultra-low-dose naloxone infusion on pain intensity after lumbar discectomy in individuals receiving patient-controlled analgesia (PCA) with morphine. In a double-blind, randomized, controlled trial, a total of 80 patients scheduled for open discectomy was randomly assigned to receive naloxone (group N) or placebo (group P). After surgery, all patients were connected to a morphine PCA pump. Both groups received 500 mL of normal saline using a continuous infusion pump through a separate intravenous line for 24 hours. However, group N received a total dose of 0.25 μg/kg/h naloxone, which was added to the normal saline infusion. All patients were asked to grade the intensity of their pain, severity of nausea, vomiting, and pruritus on a 0 to 10 visual analog scale before being discharged from the postanesthesia care unit and at 1, 6, 12, and 24 hours postoperatively. It was observed that both groups had a statistically significant (P<0.01) time trend difference for pain, nausea, and pruritus scores. A significant difference was found between the 2 groups in terms of intensity of pain, nausea, and pruritus, with the naloxone group experiencing a lower level in comparison with the placebo group. Moreover, the median (interquartile range) of morphine consumption after surgery for patients who received naloxone was 26 (24.25 to 28) mg, which is significantly (P<0.001) lower than for the placebo group, which had a median (interquartile range) of 34 (32 to 36) mg. It is concluded that infusion of ultra-low-dose naloxone (0.25 μg/kg/h) along with morphine PCA can significantly reduce pain intensity, morphine consumption, and opioid-induced nausea and pruritus after lumbar discectomy.

Colloid versus crystalloid soaked gelfoam with morphine for postoperative pain relief after lumbar laminectomy

BackgroundEpidural opiate analgesia carried by gelfoam in the epidural space is to improve the quality of perioperative pain relief. The aim of this study was to compare the analgesic efficacy of gelfoam soaked in morphine with crystalloids versus colloid versus direct application of morphine in epidural space in patients undergoing lumbar laminectomy under general anesthesia.MethodsThis study was a prospective, randomized, double-blinded trial. 75 male and female patients aged from 18 to 65 years from ASA class I or II scheduled for Lumbar laminectomy surgery were randomly divided into three equal groups: group A: (control group): 5 ml of 1 mg/ml morphine was directly instilled over intact epidural space, group B (crystalloid group): apiece of gelfoam 5 cm × 1 cm soaked in 5 mg morphine diluted with 5 ml crystalloid (0.9% sodium chloride) placed in intact epidural space; and group C (colloid group): apiece of gelfoam 5 cm × 1 cm soaked in 5 mg morphine diluted with 5 ml hydroxyethyl starch 6% (HES 6%) placed in intact epidural space by the neurosurgeon. Total analgesics, time to first analgesic request, visual analogue scale (VAS), hemodynamics, respiratory rates and adverse effects were recorded.ResultsAs regards Patient’s characteristics, age, gender, weight, ASA class and operative time were comparable in all studied groups, and groupsB and C showed less amount of analgesia, long time to analgesic request, and less main VAS. No statistically significant differences are in hemodynamics, and the incidences of side effects showed no statistically significant differences among the three groups of study.ConclusionEpidural use of gelfoam soaked by morphine in HES 6% is an effective method for post operative analgesia after lumbar laminectomy.

Planned Cesarean Delivery and Urinary Retention Associated With Spinal Morphine

Cesarean delivery (CD) is the second most commonly performed surgery in the United States. As such, prevention of complications associated with this procedure is a top priority in nursing care. Nurses at the study institution perceived that postcesarean patients experienced increased urinary retention after use of spinal morphine for postoperative pain relief. This observation prompted a review of the literature indicating that limited research had been conducted in this area. The purpose of this study was to explore the relationship of postelective CD urinary retention and dose of spinal morphine. A retrospective, quasi-experimental, three-group design was used. Records of 150 patients, ages 17 to 39, undergoing elective primary or repeat CD were examined. Morphine doses included 100, 150, and 200 mcg. No statistically significant differences were found between the three groups.

Polymorphism of μ-Opioid Receptor Gene (OPRM1:c.118A&gt;G) Might Not Protect against or Enhance Morphine-Induced Nausea or Vomiting

A cohort, double blind, and randomized study was conducted to investigate the effect of a single nucleotide polymorphism of the μ-opioid receptor at nucleotide position 118 (OPRM1:c.118A>G) on the association with the most common side effects (nausea or vomiting) induced by intravenous patient control analgesia (IVPCA) with morphine, including incidence and severity analysis. A total of 129 Taiwanese women undergoing gynecology surgery received IVPCA with pure morphine for postoperative pain relief. Blood samples were collected and sequenced with high resolution melting analysis to detect three different genotypes of OPRM1 (AA, AG, and GG). All candidates 24 h postoperatively will be interviewed to record the clinical phenotype with subjective complaints and objective observations. The genotyping after laboratory analysis showed that 56 women (43.4%) were AA, 57 (44.2%) were AG, and 16 (12.4%) were GG. The distribution of genotype did not violate Hardy-Weinberg equilibrium test. There was no significant difference neither between the severity and incidence of IVPCA morphine-induced side effects and genotype nor between the association between morphine consumption versus genotype. However, there was significant difference of the relation between morphine consumption and the severity and incidence of IVPCA morphine-induced nausea and vomiting. The genetic analysis for the severity and incidence of IVPCA morphine-induced nausea or vomiting showed no association between phenotype and genotype. It might imply that OPRM1:c.118A>G does not protect against IVPCA morphine-induced nausea or vomiting.

Pain Management in Laparoscopic Donor Nephrectomy: A Review

The management of postoperative pain is a key to patient early recovery, in particular, where the surgery was performed to benefit another human being. In recent years it has been recognized that multimodal analgesic methods are superior for postoperative pain relief. It is also imperative to remember that inadequately managed acute postoperative pain opens the doorway to possible suffering from chronic postoperative pain later. Although the laparoscopic donor nephrectomy has reduced the disincentives associated with open surgery, still significant percentage of donors suffers from postoperative pain. In the UK, patient-controlled analgesic system (PCAS) using morphine for postoperative pain relief is being used in majority of the transplant centres. Though opioids provide good analgesia, they are far from being an ideal analgesic due to their adverse effects. This paper pragmatically looks in depth on different modalities of pain management in patients undergoing laparoscopic live donor nephrectomy.

A randomised controlled trial on the efficacy and side-effect profile (nausea/vomiting/sedation) of morphine-6-glucuronide versus morphine for post-operative pain relief after major abdominal surgery

Morphine is the first choice of treatment of severe post-operative pain, despite the occurrence of often discomforting (post-operative nausea or vomiting (PONV)) and sometimes dangerous (sedation, respiratory depression) side effects. Literature data indicate that morphine’s active metabolite, morphine-6-glucuronide (M6G), is a powerful analgesic with a possibly more favourable side-effect profile. In this multi-centre randomised controlled clinical trial patients undergoing major abdominal surgery were randomised to M6G or morphine treatment. Treatment started 30–60 min prior to the end of surgery and was continued postoperatively, after patients were titrated to comfort, via patient-controlled analgesia (PCA) for 24–48 h. Pain intensity, nausea, vomiting and sedation scores were collected at regular intervals. In the study 268 patients were randomised to M6G and 249 to morphine. Withdrawal due to insufficient pain relief occurred predominantly just after surgery and was higher in the M6G group (16.8%) than in the morphine group (8.8%), suggesting a slower onset of analgesia for M6G compared to morphine. Subjects who continued on PCA remained equi-analgesic throughout the study. During the first 24 h, nausea levels showed a 27% difference in favour of M6G which narrowly failed to reach statistical significance ( P = 0.052). Sub-analysis showed a significant reduction in nausea levels in females on M6G (30% difference, P = 0.034). In all patients, similar reductions of 30–35% were observed in anti-emetic use, vomiting, PONV (a combined measure of nausea and vomiting) in favour of M6G, persisting for the first 24 h postoperatively. Reductions in sedation were observed in the first 4 h post-operative period for M6G patients.

Intrathecal morphine for postoperative pain relief.

Summary We injected 0.1 to 3 mg of morphine and atropine morphine added to 0.3% dibucaine solution into the lumbar subarachnoid space of 101 patients for supplementary intraoperative anesthesia and postoperative analgesia. Pain relief occurred within 20 to 40 minutes after injection and lasted 6 to 59 hours, with a mean duration of 25 hours, in 65 patients; the remaining 36 patients obtained unlimited pain relief for over 72 hours. However, increasing the intrathecal dose of morphine to 3 mg did not increase the duration of the analgesia. Respiratory depression was observed in 5 patients who had recieved 1.5 to 3 mg of morphine and atropine morphine. Four of these patients developed delayed respiratory depression 5 to 8 hours after the injection, and one developed early respiratory depression 1 hour after the injection. All required treatment. Other systemic side effects such as itching, nausea and vomiting occurred in a high proportion of the patients. However, in the majority of cases, these side effects were mild. A good euphoric mood appeared in 6 patients. Our experience, although limited, is that intrathecal morphine can be simultaneously used with local anesthetics effectively, safely and simply. But the optimal dose has yet been determined, and requires further investigation.

Variation in glycemia during liver resection in patients with intrathecal morphine for postoperative pain relief

Variation in glycemia during liver resection in patients with intrathecal morphine for postoperative pain relief

The Use of Intrathecal Morphine for Postoperative Pain Relief After Liver Resection: A Comparison with Epidural Analgesia

An epidural catheter is used in some institutions for postoperative analgesia after liver surgery. However, anesthesiologists may not feel comfortable leaving a catheter in the epidural space because of concern about coagulation disturbances and possible bleeding complications caused by impaired liver function. In this study, we tested a single-shot intrathecal morphine technique and compared it to a continuous epidural naropine infusion for postoperative analgesia in liver surgery. Fifty patients were randomly assigned to an epidural analgesia group (EP group; n = 25) and an intrathecal analgesia group (IN group; n = 25). The quality of analgesia assessed by a visual analog scale (VAS), the side effects, and the additional IV analgesic requirements were recorded. We did not observe any signs of cord compression. Time to first pain drug requirement was longer in the EP group compared to the IN group (25 +/- 18.5 h versus 12 +/- 10.3 h; P < 0.05). In both groups, the VAS remained less than 30 mm throughout the 48-h follow-up period. Consumption of IV morphine with a patient-controlled analgesia device in the IN group was larger (mostly from 24 to 48 h after surgery) than the EP group (12.0 +/- 5.54 mg versus 3.1 +/- 2.6 mg, respectively; P < 0.01). The incidence of vomiting was 4% in both groups, whereas the incidence of pruritus (16% versus 0%) and nausea (16% versus 4%) was more frequent in the IN group. No postdural puncture headache and no spinal hematoma occurred. After liver resection, a single dose of intrathecal morphine followed by patient-controlled morphine analgesia can provide satisfactory postoperative pain relief. The quality of this treatment, according to the VAS, is not inferior to continuous epidural analgesia up to 48 h after surgery.

Prophylactic Intravenous Ondansetron and Dolasetron in Intrathecal Morphine-Induced Pruritus: A Randomized, Double-Blinded, Placebo-Controlled Study

Pruritus is the most common side effect of intrathecal morphine for postoperative pain relief. Activation of central 5-hydroxytryptamine subtype 3 (5-HT3) receptors is one of its possible mechanisms. The role of 5-HT3 antagonists in the prevention of pruritus has not been clearly established. In a prospective, randomized, double-blind, placebo-controlled study, we evaluated the efficacy of prophylactic administration of ondansetron and dolasetron for the prevention of intrathecal morphine-induced pruritus. The patients were randomized into 3 groups to receive either 4 mg ondansetron IV (group O, n = 35), 12.5 mg dolasetron IV (group D, n = 35) or 5 mL placebo (group P, n = 35) 30 min before administration of spinal anesthesia with 10 to 17.5 mg of 0.5% hyperbaric bupivacaine and 0.25 mg of morphine for urologic, orthopedic, or vascular surgery. Patients were evaluated for incidence and severity of pruritus at arrival to the postanesthesia care unit and at 2, 4, 8, and 24 h postoperatively. The incidence and severity of pruritus was significantly less frequent in the ondansetron and dolasetron groups compared with placebo (34%, 20%, and 66% respectively, P < 0.01). Patients who received 5-HT3 antagonist reported significantly less total severity of pruritus compared with placebo during the first 8 h and the severe pruritus was observed only in patients within P group (P group: 4 of 35; 11%, O or D group: 0 of 35; 0%, P < 0.05). We conclude that the prophylactic use of ondansetron and dolasetron helps to reduce the incidence and severity of intrathecal morphine-induced pruritus.

Comparison of morphine and tramadol by patient‐controlled analgesia for postoperative analgesia after tonsillectomy in children

Tramadol is an alternative to other opioids for postoperative pain management. This prospective, randomized, double-blind study was designed to compare the analgesic efficacy of patient-controlled tramadol with patient-controlled morphine for postoperative pain after tonsillectomy in children. Sixty patients were allocated randomly to receive a patient-controlled analgesia (PCA) with either tramadol (T) or morphine (M), in a double-blind randomized study. When surgery was completed and hemostasis achieved, a standardized loading dose (0.1 mg.kg(-1) in group M, or 1 mg.kg(-1) in group T) was given. Thereafter, the children helped themselves to bolus doses (morphine (0.02 mg.kg(-1)) or tramadol (0.2 mg.kg(-1)) with lock-out times of 10 min without time limit via a PCA device. Scores for pain, sedation, nausea, and the bolus and total PCA doses, hemodynamic parameters and side effects were recorded at 5, 15, 30 min and 1, 2, 4, 6 and 24 h during PCA administration. Pain scores decreased significantly with time in both groups (P < 0.05), but were lower in group M than in group T at 1, 2 and 4 h (P < 0.05). Sedation scores increased with time in both groups (P < 0.05). However there were no significant differences in sedation scores between two groups at any study period, but nausea scores were higher in M group at 4, 6 and 24 h (P < 0.05). Intravenous patient-controlled tramadol is an alternative to patient-controlled morphine for postoperative pain relief in children after tonsillectomy. Morphine gave better postoperative pain relief, but was associated with a higher incidence of nausea than tramadol.

Is intentional unilateral epidural catheterization reliable on pain management?

Aims: In this study we aimed to compare the efficacy of intentionally directed catheter towards the operative side with midline approach and two different doses of morphine for postoperative pain relief in unilateral epidural catheterization. Method: After obtaining approval of the ethical committee and written informed consent, 36 patients aged 18–65 years, with ASA physical status I-II, scheduled for elective open reduction and osteosynthesis for malleolar fracture were included in this study. The patients were randomly divided into three groups. A Tuohy needle was advanced at a 5° to 10° angle from midline and then the bevel of the needle was rotated 90° towards the operative side in Group I and Group II. In Group III, the needle was advanced by midline approach. An epidural catheter was inserted and 4 ml of 2% lidocaine was injected through the catheter as a test dose. 20 min later, 2 mg morphine in Groups I and III and 1 mg of morphine in Group II were administered through the catheter. The infusion started with 0.2 mg hr−1 in all groups with an epidural patient controlled analgesia device. Cardiorespiratory variables and pain scores were assessed postoperatively. Side effects of morphine, total morphine consumption, the number of the incremental doses asked and received were recorded postoperatively. Statistical analysis was performed by analysis of variance, paired t-test, and chi-squared test. Results: Total morphine consumption and incidence of urinary retention were lower in Group II than in Groups I and III (p ≤ 0.01). Conclusion: Our study shows that unilateral epidural catheterization with 1 mg morphine produces adequate analgesia for postoperative pain and also reduces side effects of epidural morphine.

Preincisional Intravenous Pentoxifylline Attenuating Perioperative Cytokine Response, Reducing Morphine Consumption, and Improving Recovery of Bowel Function in Patients Undergoing Colorectal Cancer Surgery

Cytokine release during surgery can produce a long-lasting hyperalgesia. Thus, preoperatively-administered cytokine inhibitors might reduce the production of cytokines, decreasing central nervous system sensitization and improving the quality of postoperative pain relief. We investigated the hypothesis that preincisional IV pentoxifylline (PTX) treatment could attenuate the release of proinflammatory (tumor necrosis factor, interleukin (IL)-1beta, IL-6, and IL-8) and antiinflammatory (IL-1 receptor antagonist) cytokines in patients who underwent elective colorectal cancer surgery. Forty patients were randomly assigned to 1 of 2 groups of 20 each: the PTX group received a PTX 5 mg/kg IV infusion before the induction of anesthesia, whereas the control group received an equal volume of normal saline. Venous blood samples were obtained at frequent intervals. After surgery, all patients received patient-controlled analgesia (PCA) morphine for postoperative pain relief. Patients in the PTX group exhibited longer PCA trigger times, less morphine consumption, and a faster return of bowel function compared with patients in the control group. Moreover, the plasma levels of IL-6, IL-8, and IL-1 receptor antagonist were less in the treatment group, and there was no significant difference in wound infections, tumor recurrence, or metastatic rates between groups during a 2-yr follow-up.

A comparison of epidural buprenorphine with epidural morphine for postoperative analgesia following stifle surgery in dogs

Objective To compare the efficacy of epidural buprenorphine with epidural morphine for post-operative pain relief in dogs undergoing cranial cruciate ligament rupture repair.Study design A randomized, double blind clinical trial.Animals Twenty client-owned dogs with cranial cruciate ligament rupture.Methods Dogs were randomly assigned to receive either epidural buprenorphine (4 µg kg−1) or epidural morphine (0.1 mg kg−1) in a total volume of 0.2 mL kg−1. Epidural injections were performed immediately after induction of anesthesia. End-tidal halothane and CO2 were recorded every 15 minutes from the time of epidural administration of drug to extubation. A numerical rating pain score system was used by a blinded observer to evaluate analgesia beginning at extubation and continuing at specific intervals for 24 hours after surgery. Heart rate, respiratory rate, and blood pressure were recorded noninvasively at the same times. If pain score indicated moderate discomfort, rescue morphine at 1.0 mg kg−1 was administered intramuscularly.Results There were no significant differences between groups with respect to pain score, heart rate, respiratory rate, indirect blood pressure, end-tidal halothane or end-tidal CO2 at any time point. Fifty percent of dogs in the buprenorphine group and 50% of dogs in the morphine group required rescue analgesic medication. Time of systemic rescue morphine administration did not differ significantly between the two groups. There were no clinically observable side-effects from epidural administration of either drug in any of the dogs of this study.Conclusions Epidural buprenorphine is as effective as epidural morphine for the relief of postoperative hindlimb orthopedic pain in dogs.Clinical relevance Buprenorphine appears to be an effective opioid for epidural use in healthy dogs. Buprenorphine may offer certain advantages over morphine for epidural use, such as lower abuse potential and, in some clinics, reduced cost and less wastage of drug.

Advantages of Intrathecal Nalbuphine, Compared with Intrathecal Morphine, After Cesarean Delivery: An Evaluation of Postoperative Analgesia and Adverse Effects

We performed a prospective, randomized, double-blinded, multicenter study to compare the analgesic efficacy and adverse effects of intrathecal nalbuphine, at three different doses, and intrathecal morphine for postoperative pain relief after cesarean deliveries. Ninety healthy patients at full term who were scheduled for elective cesarean delivery with spinal anesthesia were enrolled in the study. They received 10 mg of hyperbaric bupivacaine 0.5% with either morphine 0.2 mg (Group 1), nalbuphine 0.2 mg (Group 2), nalbuphine 0.8 mg (Group 3), or nalbuphine 1.6 mg (Group 4). Only patients in Groups 1 and 2 reported pain during surgery. Postoperative analgesia lasted significantly longer in the morphine group, compared with the nalbuphine groups (P < 0.0001). In the nalbuphine groups, postoperative analgesia lasted longest with the 0.8-mg dose. The additional increase to 1.6 mg did not increase efficacy. The incidence of pruritus was significantly higher in Group 1 (11 of 22), compared with Group 2 (0 of 22, P < 0.0002), Group 3 (0 of 23, P < 0.0001), and Group 4 (3 of 20, P < 0.02). Postoperative nausea and vomiting were more frequent in Group 1 (5 of 22), compared with Group 2 (0 of 22, P < 0.05), Group 3 (0 of 23, P < 0.05), and Group 4 (3 of 23, not significant). There was no maternal or newborn respiratory depression. Neonatal conditions (Apgar scores and umbilical vein and artery blood gas values) were similar for all groups. This study suggests that intrathecal nalbuphine 0.8 mg provides good intraoperative and early postoperative analgesia without side effects. However, only morphine provides long-lasting analgesia. Implications Small doses of intrathecal nalbuphine produce fewer adverse effects, such as pruritus and postoperative nausea and vomiting, compared with intrathecal morphine. This may allow earlier discharge of patients from the recovery room.

In the arms of Morpheus the development of morphine for postoperative pain relief.

To analyse the historical development of morphine for postoperative analgesia and how this development was shaped by the evolution of anesthetic techniques. After a systematic review of the literature, information was gathered from primary sources. In ancient medicine, some plant derivatives were used to alleviate pain including: alcohol, cannabis, mandrake, and opium. Over the past two centuries, opium and its derivatives have become the most widely used analgesics for severe pain. Before the development of general anesthesia, surgery was only performed out of extreme necessity. It is probable that an analgesic such as opium would have been given following surgery although its use may not have been recorded. The first description of postoperative opium was by James Moore in 1784. Morphine was isolated from opium by Friedrich Serturner in 1805. However, it was not until the development of the hypodermic needle and syringe nearly 50 yr later that the use of morphine became widespread. Over the last century, various delivery systems for morphine have been developed including subarachanoid and epidural injection, and more recently patient-controlled intravenous, epidural and intranasal analgesia. In addition, many new opioids have been synthesized. Since its isolation from opium almost 200 yr ago, morphine remains the most widely used analgesic and the standard against which all new opioids for postoperative pain relief are compared.

Endogenous morphine levels increase following cardiac surgery as part of the antiinflammatory response?

Exogenous morphine downregulates the activity of immunocompetent cells such as lymphocytes, granulocytes and macrophages. Furthermore, morphine increases the secretion of CRH, ACTH and glucocorticoids, i.e. substances with inhibitory effects on the immune system. In the present study we tested the hypothesis that endogenous morphine production is increased as part of the antiinflammatory response to cardiac surgery. Sixteen patients submitted to elective coronary artery bypass grafting (CABG) surgery were randomized to either thoracic epidural analgesia combined with general anaesthesia (group I) or high-dose fentanyl anaesthesia (group II). Patients in group I did not receive morphine while patients in group II received systemic morphine for postoperative pain relief. From each patient 18 blood samples were taken perioperatively and tested for morphine. Furthermore, monocyte function with respect to motility and shape was determined by computer-assisted image analysis. A steep increase in plasma morphine concentrations was demonstrated on the first postoperative day in patients in group I (not given morphine). Plasma morphine levels remained significantly elevated during the following five postoperative days. Patients in group II given morphine as pain treatment showed a larger and earlier morphine peak related to the morphine administration. Computer-assisted image analysis of leukocyte behaviour revealed a biphasic increase in cell motility. In conclusion, we demonstrate for the first time that endogenous morphine levels increase after the trauma of surgery. We surmise that morphine is part of the antiinflammatory response to cardiac surgery.