Effect of combining naloxone and morphine for intravenous patient-controlled analgesia

BACKGROUND: An early study showed that a naloxone infusion decreased the incidence of morphine-related side effects from intravenous patient-controlled analgesia. The authors tested the hypothesis that a more convenient combination of morphine and naloxone via patient-controlled analgesia would decrease the incidence of side effects compared to morphine alone. METHODS: Patients scheduled for hysterectomy under general anaesthesia were enrolled in a double-blind, randomized, placebo-controlled trial. Patients received a standardized general anesthetic and postoperative patient-controlled analgesia. They were randomized to receive 60 mg patient-controlled analgesia morphine in 30 ml saline or 60 mg morphine in 30 ml saline with naloxone 0.8 mg. Parameters for patient-controlled analgesia were a 1-mg bolus of morphine with a 5-min lockout and no background infusion. Patient recall of nausea, vomiting, itching, and pain (at rest and with movement) were assessed at 6 and 24 h postoperatively by verbal rating score. Pain was also assessed by a 0- to 100-mm visual analog score, and sedation was assessed by an observer. The amount of morphine used and the requirements for symptomatic treatment were also recorded. RESULTS: Ninety-two patients completed the study, with no significant differences in outcomes between groups. At 24 h, the incidence of nausea was 84.8% in each group; the incidence of pruritus was 56.5% in the naloxone group and 58.7% in the placebo group. There were also no differences in symptomatic treatment requirements, pain scores, morphine use, or sedation between groups. The median dose of naloxone received equated to 0.38 microg x kg-1 x h-1 over 24 h. CONCLUSIONS: There was no benefit from administering naloxone combined with morphine via patient-controlled analgesia.     

Opioid-sparing Effects of a Low-dose Infusion of Naloxone in Patient-administered Morphine Sulfate

Background: A naloxone infusion is effective in reducing epidural and intrathecal opioid-related side effects. The use of naloxone infusion concomitant with intravenous morphine patient-controlled analgesia (PCA) has not been evaluated, probably because of an expected direct antagonism of the systemic opioid effect. The authors compared the incidence of morphine-related side effects and the quality of analgesia from two small doses of naloxone infusion.

Methods: Sixty patients classified as American Society of Anesthesiologists physical status 1, 2, or 3 who were scheduled for total abdominal hysterectomies were enrolled in the study. Patients received a standardized general anesthetic. In the postanesthetic care unit, patients received morphine as a PCA. They were randomized to receive either 0.25 micro gram [center dot] kg sup -1 [center dot] h sup -1 naloxone (low dose), 1 micro gram [center dot] kg sup -1 [center dot] h sup -1 (high dose), or saline (placebo) as a continuous infusion. Verbal rating scores for pain, nausea, vomiting, and pruritus; sedation scores; requests for antiemetic; and morphine use were recorded for 24 h. Blood pressure, respiratory rate, and oxyhemoglobin saturation were also monitored.

Results: Sixty patients completed the study. Both naloxone doses were equally effective in reducing the incidence of nausea, vomiting, and pruritus compared with placebo (P < 0.05 by the chi-squared test). There was no difference in the verbal rating scores for pain between the groups. The cumulative morphine use was the lowest in the low-dose group (42.3 +/- 24.1 mg; means +/- SD) compared with the placebo (59.1 +/- 27.4 mg) and high-dose groups (64.7 +/- 33.0 mg) at 24 h (P < 0.05 by analysis of variance). There was no incidence of respiratory depression (< 8 breaths/min) and no difference in sedation scores, antiemetic use, respiratory rate, and hemodynamic parameters among the groups.     

Pain following craniotomy: a preliminary study comparing PCA morphine with intramuscular codeine phosphate

We have performed a prospective randomised trial of 30 patients undergoing craniotomy to compare intramuscular codeine phosphate with patient-controlled analgesia using morphine 1 mg bolus with a 10-min lockout and no background infusion. For 24 h postoperatively, pain, nausea, Glasgow coma score, respiratory rate and sedation score were assessed. There was a wide variation in the amounts of morphine requested by the patients in the patient-controlled analgesia group in the first 24 h postoperatively (range 2–79 mg, median 17 mg). There was a small, but non-significant, reduction in pain scores in the patient-controlled analgesia group. There were no significant differences between the two groups in respect of nausea and vomiting, sedation score or respiratory rate. No major adverse effects were noted in either group. Patient-controlled analgesia with morphine is an alternative to intramuscular codeine phosphate in neurosurgical patients which merits further investigation.     

Patient-controlled analgesia following caesarean section: a comparison of morphine and meptazinol

Forty-eight women were investigated in a prospective double-blind study and randomised to receive intravenous patient-controlled analgesia (PCA) with meptazinol or morphine following elective caesarean section. Women received PCA boluses of 1 mg morphine or 10 mg meptazinol with no background infusion. Total drug consumption measured over a 24 h period, pain (visual analogue scores), sedation scores, incidence of nausea and vomiting, and requests for rescue analgesia were compared. Both meptazinol and morphine delivered via PCA provide satisfactory analgesia after caesarean section. There was no statistically significant difference in pain scores (P = 0.47) or the incidence of side-effects (nausea/vomiting P = 0.076, sedation P = 0.63) between the two drugs. Meptazinol is more expensive and offers no clinical advantages in this group of patients.     

Intraoperative Remifentanil Infusion Does Not Increase Postoperative Opioid Consumption Compared with 70% Nitrous Oxide

Background: Remifentanil is commonly used to replace nitrous oxide in general anesthesia to avoid the side effects of the latter. However, there are reports that intraoperative remifentanil infusion can lead to acute opioid tolerance. In this study, the authors tried to determine the dose of remifentanil comparable in efficacy to 70% nitrous oxide and to evaluate its effect on postoperative pain and morphine consumption after colorectal surgery using isoflurane anesthesia.

Methods: Sixty adult patients undergoing open colorectal surgery were randomly assigned to receive either remifentanil or 70% nitrous oxide along with isoflurane anesthesia. After morphine analgesia titration in the postanesthesia care unit, patient-controlled analgesia was commenced. Morphine consumption and pain were scored at rest and during cough or movement for 24 h.

Results: The mean remifentanil infusion rate was 0.17 [mu]g [middle dot] kg-1 [middle dot] min-1. The median visual analog pain score on arrival in the postanesthesia care unit was 1 (0-10) in the nitrous oxide group and 3 (0-9) in the remifentanil group (P < 0.05). Otherwise, there was no difference in pain scores at 5, 10, and 15 min and no difference in the total morphine consumption during the stay in the postanesthesia care unit. The two groups had similar total morphine consumption in the first 24 h and pain scores at rest and during movement. The incidence of postoperative nausea and vomiting was 10% in both groups. There was no difference in the sedation scores.     

Acupressure for postoperative nausea and vomiting in gynaecological patients receiving patient-controlled analgesia

BACKGROUND AND OBJECTIVES: To evaluate the effectiveness of acupressure in preventing nausea and vomiting in patients undergoing gynaecological operations and receiving a patient-controlled analgesia device. METHODS: Patients aged between 40 and 65 yr were included. Exclusion criteria were obesity, diabetes mellitus, and history of motion sickness, postoperative nausea and vomiting, or smoking. Patients were randomized into one of two groups, acupressure and control. In the acupressure group, acupressure bands were placed on both wrists with the plastic bead positioned at the P6 point. In controls, beads were placed at a non-acupoint site. All patients received a standard general anaesthetic. Postoperatively, patients were connected to a patient-controlled analgesia device with morphine (loading dose 5 mg, background infusion 1 mg h-1, bolus dose 1 mg and lock-out time 10 min). Pain and sedation scores, respiratory rate, heart rate, arterial pressure and oxygen saturation were recorded for 24 h. Metoclopramide 10 mg was administered intravenously as a rescue antiemetic. RESULTS: Fifty patients received acupressure and 50 were controls. In the acupressure group, 33% of patients had nausea compared with 63% controls. The cumulative incidence of vomiting at 24 h was 25% with acupressure and 61% in controls. The incidence of nausea, vomiting and antiemetic use was significantly lower with acupressure. CONCLUSIONS: Acupressure at the P6 meridian point is an effective alternative for the prevention of nausea and vomiting in patients receiving patient-controlled analgesia with morphine after gynaecological surgery.     

The effects of a small-dose naloxone infusion on opioid-induced side effects and analgesia in children and adolescents treated with intravenous patient-controlled analgesia: a double-blind, prospective, randomized, controlled study

Opioids are frequently associated with side effects such as nausea, vomiting, and pruritus. We hypothesized that a prophylactic, continuous small-dose naloxone infusion would reduce the incidence of opioid-induced side effects without affecting analgesia or opioid consumption. In this prospective, double-blind, randomized, controlled clinical trial, we studied 46 postoperative patients (M:F, 21:25), averaging 14 +/- 2.5 yr and 53 +/- 17 kg, at the start of morphine IV patient-controlled analgesia. Patients were randomized to either saline (control, n = 26) or naloxone 0.25 microg . kg(-1) . h(-1) (n = 20). We found that the incidence and severity of pruritus (77% versus 20%; P < 0.05) and nausea (70% versus 35%; P < 0.05) was significantly more frequent in the placebo group compared with the naloxone group. Morphine consumption (1.02 +/- 0.41 mg . kg(-1) . d(-1) versus 1.28 +/- 0.61 mg . kg(-1) . d(-1)), pain scores at rest (4 +/- 2 versus 3 +/- 2), and pain scores with coughing (6 +/- 2 versus 6 +/- 2) were not different. We conclude that, in children and adolescents, a small-dose naloxone infusion (0.25 microg . kg(-1) . h(-1)) can significantly reduce the incidence and severity of opioid-induced side effects without affecting opioid-induced analgesia. When initiating morphine IV patient-controlled analgesia for the treatment of moderate to severe pain, clinicians should strongly consider starting a concomitant small-dose naloxone infusion.     

Patient-controlled alfentanil

We have compared the opioid effects of a patient-demand, target-controlled infusion of alfentanil (n = 10), with patient-controlled bolus administration of morphine (n = 10) following major spinal surgery in Chinese patients aged from 11 to 67 years. The same general anaesthesia regimen was used in all patients. One group of patients were given intra-operative morphine analgesia followed by postoperative intravenous morphine patient-controlled analgesia, while the other group received an intra-operative target-controlled infusion of alfentanil. Following surgery, the alfentanil group were given control of a handset and were able to increase the target alfentanil plasma level in 5ng.ml^-1 increments with a 2-min lockout interval. If analgesia was not demanded within a 15-min period, the computer reduced the target concentration by 5ng.ml^-1. All patients had continuous pulse oximetry monitoring and hourly recording of pain, sedation, nausea scores and respiratory rate. Patients receiving alfentanil had the target concentration noted hourly and four blood samples taken during the first 24 h for measurement of plasma alfentanil concentrations by high performance liquid chromatography. The alfentanil infusion system was equally effective as an analgesic technique when compared with morphine patient-controlled analgesia. There were no hypoxaemic episodes (oxygen saturation <94%), no difference in sedation scores and the incidence of nausea (30%) was the same in both groups. There was a significantly (p < 0.001) lower respiratory rate in the alfentanil group compared with patients receiving morphine at, clinically assessed, equianalgesia. The predicted plasma alfentanil concentrations increased rapidly from about 30ng.ml^-1 during the first 4 h to around 100ng.ml^-1 at the end of the 24-h study period. The precision of the target-controlled infusion system was 75.4% and the mean prediction error (bias) 58.1%, suggesting an underestimation of the measured alfentanil concentrations by the alfentanil infusion system in these Chinese patients.     

Comparison of epidurally administered sufentanil, morphine, and sufentanil-morphine combination for postoperative analgesia

Postoperative analgesia provided by epidurally administered sufentanil and/or morphine was evaluated in 45 patients recovering from major gynecologic surgery. At the first complaint of pain in the Postanesthesia Care Unit, patients received a single epidural bolus of 30 micrograms sufentanil (group A), 5 mg morphine (group B), or 30 micrograms sufentanil plus 3 mg morphine (group C) in a randomized blinded fashion. Analgesic efficacy was assessed throughout the 24-h study period with 10-cm visual analog scales. The need for additional postoperative analgesia (patient-controlled analgesia, 1 mg of morphine every 6 min as necessary) and the incidence of adverse effects were also assessed. Patients receiving sufentanil (groups A and C) had significantly faster onset of analgesia than did patients given morphine alone (group B, P less than 0.05). Group B subjects experienced the longest duration of analgesia (B vs A and C, P less than 0.05) and required significantly less patient-controlled analgesia (morphine) than patients in group A (P less than 0.05). No patient developed clinically significant respiratory depression or excessive sedation, and there were no intergroup differences in incidence of pruritus or nausea (P value not significant). The data indicate that a mixture of sufentanil and morphine provides either a more rapid onset of epidural analgesia or reduced patient-controlled analgesia narcotic requirement than respective doses of each agent administered alone.     

Effects of Prophylactic Nalmefene on the Incidence of Morphine-related Side Effects in Patients Receiving Intravenous Patient-controlled Analgesia

Background: Opioid-related side effects associated with intravenous patient-controlled analgesia can be reduced by a low-dose naloxone infusion. The influence of nalmefene, a pure opioid antagonist with a longer duration of action, on opioid-related side effects has not been evaluated. This study was designed to determine the dose-response relation for nalmefene for the prevention of morphine-related side effects in patients receiving intravenous patient-controlled analgesia.

Methods: One hundred twenty women undergoing lower abdominal surgery were enrolled in the study. General anesthesia was induced using thiopental and rocuronium and maintained with desflurane, nitrous oxide, and fentanyl or sufentanil. All patients received neostigmine and glycopyrrolate to reverse residual neuromuscular blockade. No prophylactic antiemetics were administered. At the end of surgery, patients were randomized to receive saline, 15 [micro sign]g nalmefene, or 25 [micro sign]g nalmefene intravenously. The need for antiemetic and antipruritic drugs and the total consumption of morphine during the 24-h study were recorded. The incidences of postoperative nausea, vomiting, pruritus, and pain were recorded 30 min after patients were admitted to the postanesthesia care unit. In addition, patient remembrance of these side effects was noted at 24 h after operation.

Results: The need for antiemetic and antipruritic medications during the 24-h study period was significantly lower in the patients receiving nalmefene compared with those receiving placebo. However, the need to treat side effects was similar in the two nalmefene groups. Prophylactic administration of nalmefene reduced the patients remembrance of nausea and itching as assessed 24 h after operation. Although the total consumption of morphine during the 24-h study period was similar in the three groups, retrospectively patients who received nalmefene characterized their pain as less severe in the previous 24 h.     

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

BACKGROUND: 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. METHOD: 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. RESULTS: 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). CONCLUSION: 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.     

Postoperative nausea and vomiting in children using patient-controlled analgesia: the effect of prophylactic intravenous dixyrazine

BACKGROUND: Although patient-controlled analgesia (PCA) with morphine provides a high degree of satisfactory postoperative analgesia in children, it is often associated with a high incidence of postoperative nausea and vomiting (PONV). Our aim in this study was to evaluate the prophylactic effect of dixyrazine, a phenothiazine with proven anti-emetic properties. METHODS: The incidence of nausea and vomiting was studied in 60 children using PCA after major surgery. The patients were randomised to receive either dixyrazine 0.25 mg kg-1 or placebo on the induction of anaesthesia in a double-blind, placebo-controlled design. The anaesthetic technique was standardised. The PCA pump was programmed to deliver bolus doses of morphine of 20 micrograms kg-1 with a continuous background infusion of 8-10 micrograms kg-1 h-1. Nausea, vomiting, sedation and pain scores were noted every 3 h for a period of 24 h. RESULTS: The morphine consumption of morphine was the same in both groups. During the stay in the recovery room the incidence of vomiting was 3% in the dixyrazine group compared to 30% in the placebo group (P < 0.05). On the ward, 57% versus 83% of the children vomited (P < 0.05). Rescue antiemetics were significantly lower, 30%, in the dixyrazine group compared to 60% in the placebo group (P < 0.05). Higher sedation scores were recorded for the dixyrazine group in the recovery room. No other adverse effects were found. CONCLUSION: A significant number of children using PCA with morphine after major surgery experience PONV. Although prophylactic dixyrazine reduces the incidence and severity of vomiting, the incidence still remains high.     

Development of acute opioid tolerance during infusion of remifentanil for pediatric scoliosis surgery

We tested the hypothesis that continuous intraoperative infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery. Thirty adolescents were randomly assigned to receive an intraoperative analgesic regimen consisting of continuous remifentanil infusion or intermittent morphine alone. Postoperative analgesic consumption was assessed with a patient-controlled analgesia device that was used to self-administer morphine. Cumulative postoperative morphine consumption, pain scores, and sedation scores were recorded by a blinded investigator every hour for the first 4 h postoperatively and then every 4 h for a total of 24 h. Cumulative morphine consumption in the remifentanil group was significantly more than that in the morphine group at each time point in the initial 24 h after surgery (P < 0.0001). At 24 h after surgery, cumulative morphine consumption was 30% greater in the remifentanil group (1.65 +/- 0.41 mg/kg) than in the morphine group (1.27 +/- 0.32 mg/kg) (95% confidence interval for the difference, 0.11 to 0.65 mg/kg). Differences in pain and sedation scores were not statistically significant. These data suggest that intraoperative infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery.     

Effects of epidural naloxone on pruritus induced by epidural morphine: a randomized controlled trial

BACKGROUND: Epidural morphine produces prolonged analgesia but has many side effects including pruritus. Naloxone is an antagonist that can reverse the side effects of morphine. METHOD: We studied the effects of continuously administered epidural naloxone mixed with morphine on side effects and analgesia in a randomized, double blind, two-armed study. Fifty-eight pregnant women undergoing cesarean section were enrolled. All patients received a 4-mg epidural bolus of morphine in the post-anesthetic care unit. After this, patients in group M (n=28) received continuous epidural morphine (6 mg over 48 h) in 0.1% bupivacaine; patients in group N (n=30) received an epidural infusion containing naloxone (1.2 mg over 48 h) and morphine (6 mg over 48 h) in 0.1% bupivacaine. The infusion rate was 2 mL/h. RESULTS: The incidence (82% versus 47%) and severity of pruritus were lower in group N than group M (P=0.001). There were no significant differences in pain score or in the incidence of nausea, vomiting or urinary disturbance between groups. CONCLUSION: Continuous epidural infusion of naloxone combined with morphine is effective in reducing the incidence and severity of pruritus induced by epidural morphine.     

Double-blind, Randomized Comparison of Ondansetron and Intraoperative Propofol to Prevent Postoperative Nausea And Vomiting

Background: Breast surgery is associated with a high incidence of postoperative nausea and vomiting. Propofol and prophylactic administration of ondansetron are associated with a lower incidence of postoperative nausea and vomiting. To date no comparison of these two drugs has been reported. A randomized study was done to compare the efficacy of ondansetron and intraoperative propofol given in various regimens.

Methods: Study participants included 89 women classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled for major breast surgery. Patients were randomly assigned to one of four groups. Group O received 4 mg ondansetron in 10 ml 0.9% saline and groups PI, PIP, and PP received 10 ml 0.9% saline before anesthesia induction. Group O received thiopental, isoflurane, nitrous oxide-oxygen, and fentanyl for anesthesia. Group PI received propofol, isoflurane, nitrous oxide-oxygen, and fentanyl. Group PIP received propofol, isoflurane, nitrous oxide-oxygen, and fentanyl. Thirty minutes before expected skin closure, isoflurane was discontinued and 50 to 150 micro gram [centered dot] kg sup -1 [centered dot] min sup -1 propofol was given intravenously to maintain anesthesia. Group PP received propofol for induction and maintenance of anesthesia, nitrous oxide-oxygen, and fentanyl. Postoperative pain relief was provided with morphine administered by a patient-controlled analgesia pump. The incidence of nausea and vomiting, requests for rescue antiemetic and sedation, pain scores, and hemodynamic data were recorded for 24 h.

Results: Within 6 h of surgery, groups O and PP had a lower incidence of nausea compared with groups PI and PIP (P < 0.05). Fewer patients in group PP (19%) vomited during the 24-h period compared with groups O (48%), PI (64%), and PIP (52%) (P < 0.05). The incidence of antiemetic use was also less in group PP (P < 0.05). Patients in group PP had lower sedation scores at 30 min and at 1 h (P < 0.05). There were no differences among the groups in pain scores, blood pressure, heart rate, respiratory rate, and incidence of pruritus.     

Patient-maintained analgesia with target-controlled alfentanil infusion after cardiac surgery: a comparison with morphine PCA

The performance of a patient-demand, target-controlled alfentanil infusion system was compared with that of a traditional morphine patient-controlled analgesia (PCA) pump in 120 adult patients after cardiac surgery. Patients were randomized to one of the two PCA systems for their postoperative analgesia in the intensive care unit and pain, nausea and sedation scores were recorded every 4 h for the first 24 h. Episodes of hypoxaemia, myocardial ischaemia and haemodynamic instability were also recorded. In patients using the alfentanil system the overall median visual analogue pain score was 2.3 (95% Cl 2.3-2.8) compared with 3.0 (95% Cl 2.7-3.2) in those using morphine PCA (P < 0.05), but both systems delivered high-quality analgesia. The two groups did not differ with respect to the overall sedation scores, the frequency of postoperative nausea and vomiting, haemodynamic instability, myocardial ischaemia or hypoxaemia.      

Patient-controlled analgesia with morphine and droperidol following caesarean section under spinal anaesthesia

Background: The addition of droperidol to morphine for patient-controlled analgesia reduces the incidence of nausea and vomiting, but may result in unwanted side effects.
Method: We studied 40 women randomised to receive morphine sulphate with or without added droperidol (10mg droperidol/60mg morphine) by patient-controlled analgesia following elective caesarean section under spinal anaesthesia.
Results: Median morphine demand in the 20h after surgery was 74mg with morphine alone, and 53mg with added droperidol, the median consumption of which was 8.8mg. The incidence of nausea was reduced from 80% to 38.8% ( P <0.01), and that of emesis from 55% to 16.7% ( P <0.05) by the addition of droperidol. Psychomotor function was significantly impaired to a similar degree in both groups and there was no significant difference in sedation scores or pain scores. Subjective drowsiness which resulted in withdrawal from the study occurred in two patients, both of whom were receiving droperidol, and though all patients who completed the study were satisfied with their analgesia overall, significantly more of those receiving unsupplemented morphine (11/19 compared with 4/18, P <0.05) described it as excellent.
Conclusion: The addition of droperidol 10mg to morphine 60mg for PCA following caesarean section under spinal anaesthesia reduces the incidence of nausea and emesis, but may result in drowsiness, limiting the usefulness of the technique.     

Remifentanil versus Morphine Analgesia and Sedation for Mechanically Ventilated Critically Ill Patients: A Randomized Double Blind Study

Background: The rapid onset and offset of action of remifentanil could make it quickly adjustable to the required level of sedation in critically ill patients. The authors hypothesized that the efficacy of a remifentanil-based regimen was greater than that of a morphine-based regimen.

Methods: Forty intent-to-treat patients were randomly allocated to receive a blinded infusion of either remifentanil 0.15 [mu]g[middle dot]kg-1[middle dot]min-1 or morphine 0.75 [mu]g[middle dot]kg-1[middle dot]min-1. The opioid infusion was titrated, in the first intent, to achieve optimal sedation defined as Sedation Agitation scale of 4. A midazolam open-label infusion was started if additional sedation was required.

Results: The mean percentage hours of optimal sedation was significantly longer in the remifentanil group (78.3 +/- 6.2) than in the morphine group (66.5 +/- 8.5). This was achieved with less frequent infusion rate adjustments (0.34 +/- 0.25 changes/h) than in the morphine group (0.42 +/- 0.22 changes/h). The mean duration of mechanical ventilation and extubation time were significantly longer in the morphine group (18.1 +/- 3.4 h, 73 +/- 7 min) than in the remifentanil group (14.1 +/- 2.8 h, 17 +/- 6 min), respectively. Remifentanil mean infusion rate was 0.13 +/- 0.03 [mu]g[middle dot]kg-1[middle dot]min-1, whereas morphine mean infusion rate was 0.68 +/- 0.28 [mu]g[middle dot]kg-1[middle dot]min-1. More subjects in the morphine group (9 of 20) than in the remifentanil group (6 of 20) required midazolam. The incidence of adverse events was low and comparable across the two treatment groups.     

Effects of Perioperative Analgesic Technique on the Surgical Outcome and Duration of Rehabilitation after Major Knee Surgery

Background: Continuous passive motion after major knee surgery optimizes the functional prognosis but causes severe pain. The authors tested the hypothesis that postoperative analgesic techniques influence surgical outcome and the duration of convalescence.

Methods: Before standardized general anesthesia, 56 adult scheduled for major knee surgery were randomly assigned to one of three groups, each to receive a different postoperative analgesic technique for 72 h: continuous epidural infusion, continuous femoral block, or intravenous patient-controlled morphine (dose, 1 mg; lockout interval, 7 min; maximum dose, 30 mg/4 h). The first two techniques were performed using a solution of 1% lidocaine, 0.03 mg/ml morphine, and 2 [micro sign]g/ml clonidine administered at 0.1 ml [middle dot] kg-1 [middle dot] h-1. Pain was assessed at rest and during continuous passive motion using a visual analog scale. The early postoperative maximal amplitude of knee flexion was measured during continuous passive motion at 24 h and 48 h and compared with the target levels prescribed by the surgeon. To evaluate functional outcome, the maximal amplitudes were measured again on postoperative day 5, at hospital discharge (day 7), and at 1- and 3-month follow-up examinations. When the patients left the surgical ward, they were admitted to a rehabilitation center, where their length of stay depended on prospectively determined discharge criteria.

Results: The continuous epidural infusion and continuous femoral block groups showed significantly lower visual analog scale scores at rest and during continuous passive motion compared with the patient-controlled morphine group. The early postoperative knee mobilization levels in both continuous epidural infusion and continuous femoral block groups were significantly closer to the target levels prescribed by the surgeon than in the patient-controlled morphine group. On postoperative day 7, these values were 90 [degree sign] (60-100 [degree sign]) (median and 25th-27th percentiles) in the continuous epidural infusion group, 90 [degree sign] (60-100 [degree sign]) in the continuous femoral block group, and 80 [degree sign] (60-100 [degree sign]) in the patient-controlled morphine group (P < 0.05). The durations of stay in the rehabilitation center were significantly shorter: 37 days (range, 30-45 days) in the continuous epidural infusion group, 40 days (range, 31-60 days) in the continuous femoral block group, and 50 days (range, 30-80 days) in the patient-controlled morphine group (P < 0.05). Side effects were encountered more frequently in the continuous epidural infusion group.     

No morphine sparing effect of ketamine added to morphine for patient-controlled intravenous analgesia after uterine artery embolization

Background: Pain following embolization of the uterine arteries (UAEs) is variable and may be very severe requiring large doses of parenteral opioids for relief. The present study tested the hypothesis that the addition of ketamine to IV patient-controlled morphine reduces the amount of morphine required for pain-control during the first 24 h after UAE embolization.
Methods: Fifty-six patients undergoing UAE embolization for treatment of symptomatic uterine leiomyomata were randomized to receive either 2 mg/ml of morphine (Control group, n =30) or 2 mg/ml of both morphine and ketamine (Ketamine group, n =26) by IV patient-controlled analgesia (IV-PCA). Pump settings were bolus dose 1 ml, lockout 10 min, no background infusion. In addition, all patients received diclofenac and acetaminophen for pain relief. Pain scores, morphine consumption and adverse events like nausea, vomiting, itching, visual disturbances, anxiety, dreaming and hallucinations, if any, were recorded for 24 h after embolization.
Results: The mean ± SD 24-h consumption of patient-controlled morphine was 38.3 ± 21.0 mg in the Ketamine group vs. 33.3 ± 18.3 mg in the Control group (NS). The difference between the means was 5.0 mg (95% confidence interval: −5.7; 15.6). One patient in the Ketamine group vs. none in the Control group experienced auditory hallucinations.
Conclusion: Studying an unselected group of patients undergoing embolization of the UAEs for treatment of symptomatic uterine leiomyomata under conditions of basal analgesia with acetaminophen and diclofenac, we failed to demonstrate any morphine-sparing effect of IV-PCA ketamine and morphine compared with IV-PCA morphine alone.