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 mug . kg . min. 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. CONCLUSION: The substitution of 70% nitrous oxide with remifentanil at a mean infusion rate of 0.17 mug . kg . minute for colorectal surgery did not affect postoperative opioid consumption.     

The efficacy of intravenous 0.15 versus 0.25 mg/kg intraoperative morphine for immediate postoperative analgesia after remifentanil-based anesthesia for major surgery

We evaluated the effect of perioperative administration of two doses of morphine for postoperative analgesia after remifentanil-based anesthesia. The prospective, randomized study included 245 patients from 33 centers. All patients were scheduled for abdominal or urological surgery lasting more than 1 h. General anesthesia used remifentanil as the perioperative opioid (1 microg/kg as a bolus then, 0.5 microg/kg as a continuous infusion). A morphine bolus of 0. 15 mg/kg (0.15-mg group) or 0.25 mg/kg (0.25-mg group) was administered 30 min before the end of surgery. In the postanesthesia care unit, pain scores for patients were evaluated by using behavioral pain scores of 1-3, verbal pain scores of 0-3, and visual analog scale scores of 0-10). Postoperative analgesia was obtained by a morphine titration (3 mg every 5 min). Demographic and surgery characteristics were similar in both groups. The delay for first demand of morphine was similar in the 0.15-mg and the 0.25-mg groups (26 [9-60] and 30 [10-60] min, respectively). The frequency of morphine titration was similar in both groups (75% and 66%, respectively). The amount of morphine used in the postanesthesia care unit was smaller in the 0.25-mg group (0.16 [0.0-1.25] vs 0.10 [0.0-0.56] mg/kg; P = 0.008). In the 0.25-mg group, the behavioral pain score was lower at 15 min, the verbal pain score was lower at 60 min (P < 0.001), and similar at 30 min. The visual analog scale pain score at 30 min and 60 min was similar in both groups. The incidence of minor side effects was similar in both groups. However, three cases of postoperative respiratory depression occurred in the 0.25-mg group compared with no cases in the 0.15-mg group. In conclusion, perioperative administration of morphine alone does not provide entirely adequate immediate postoperative pain control after remifentanil-based anesthesia in major surgery. Implications: The administration of 0.15 or 0.25 mg/kg perioperative morphine during remifentanil-based anesthesia for major surgery does not preclude additional morphine administration in the postanesthesia care unit. The larger dose of 0.25 mg/kg slightly improves postoperative analgesia; however, it may be responsible for postoperative respiratory depression.     

七氟烷、地氟烷或丙泊酚麻醉术后疼痛和镇痛药需求量的比较

背景全身麻醉药可产生伤害反应从而影响手术后疼痛,在一些手术后疼痛的研究中,均没有考虑全麻药对镇痛药需要量的影响,仅有最近一项研究显示丙泊酚麻醉的手术后镇痛效果比异氟烷麻醉好。方法前瞻性、随机、双盲研究,记录在七氰烷、地氟烷或丙泊酚麻醉下行腹式子宫切除术或子宫肌瘤切除手术患者手术后2、4、8、和24小时吗啡的需要量和疼痛评分（疼痛视觉模拟评分,VAS）,手术中维持BIS35～45。同时记录患者送至麻醉监护室时的疼痛评分。结果3组患者手术后2、4、8或24小时,吗啡累积消耗量无差异（P=0．50）。手术后24小时内吗啡消耗量：七氟烷组28±13．8mg;地氟垸组25±11.7mg;丙泊酚组27±16．1mg。疼痛评分在患者转运至麻醉监护室即刻、手术后2、4、8和24小时,分别在静息及咳嗽状态下评估,显示3组间无差异（静息时P=0．40、0．39、0．50、0．47、0．06;咳嗽后P=0．67、0．45、0,22、0．26、0．29）．结论手术后24小时吗啡消耗量和手术后疼痛情况在七氟烷、地氟烷或丙泊酚3组间差异无显著性。     

Acute Opioid Tolerance: Intraoperative Remifentanil Increases Postoperative Pain and Morphine Requirement

Background: Rapid development of acute opioid tolerance is well established in animals and is more likely to occur with large doses of short-acting drugs. The authors therefore tested the hypothesis that intraoperative remifentanil administration results in acute opioid tolerance that is manifested by increased postoperative pain and opioid requirement.

Methods: Fifty adult patients undergoing major abdominal surgery were randomly assigned to two anesthetic regimens: (1) desflurane was kept constant at 0.5 minimum alveolar concentrations and a remifentanil infusion was titrated to autonomic responses (remifentanil group); or (2) remifentanil at 0.1 [mu]g [middle dot] kg-1 [middle dot] min-1 and desflurane titrated to autonomic responses (desflurane group). All patients were given a bolus of 0.15 mg/kg morphine 40 min before the end of surgery. Morphine was initially titrated to need by postanesthesia care nurses blinded to group assignment. Subsequently, patients-who were also blinded to group assignment-controlled their own morphine administration. Pain scores and morphine consumption were recorded for 24 postoperative h.

Results: The mean remifentanil infusion rate was 0.3 +/- 0.2 [mu]g [middle dot] kg-1 [middle dot] min-1 in the remifentanil group, which was significantly greater than in the desflurane group. Intraoperative hemodynamic responses were similar in each group. Postoperative pain scores were significantly greater in the remifentanil group. These patients required morphine significantly earlier than those in the desflurane group and needed nearly twice as much morphine in the first 24 postoperative h: 59 mg (25-75% interquartile range, 43-71) versus 32 mg (25-75% interquartile range, 19-59;P < 0.01).     

Ropivacaine epidural anesthesia and analgesia versus general anesthesia and intravenous patient-controlled analgesia with morphine in the perioperative management of hip replacement. Ropivacaine Hip Replacement Multicenter Study Group.

The aim of our study was to compare epidural anesthesia and analgesia (EDA) with ropivacaine versus general anesthesia followed by IV patient-controlled analgesia with morphine (GA/PCA) after hip replacement regarding pain, side effects, and discharge from the postanesthesia care unit. After ethics committee approval, randomization, and informed consent, 90 patients were enrolled. In Group EDA, epidural anesthesia (ropivacaine 10 mg/mL, 15-25 mL) was followed by an epidural infusion (2 mg/mL, 4-6 mL/h for 24 h, plus top-up doses of 6-10 mL for 48 h). GA/PCA patients received general anesthesia (isoflurane/N2O/fentanyl) followed by IV patient-controlled analgesia with morphine postoperatively. Pain was assessed by using visual analog scales (0-100 mm) at rest and during physiotherapy. Pain at rest was less in the EDA (n = 43) group than in the GA/PCA (n = 45) group (at 10 h: 11.8+/-12.9 vs. 28.4+/-17.1 [P< 0.001]; at 24 h: 14.3+/-11.7 vs. 24.0+/-17 [P<0.01]; in 48 h: 14.3+/-9.3 vs. 21.1+/-17.4 [P = 0.1]). Whereas EDA patients were deemed ready for discharge from the postanesthesia care unit earlier than GA/PCA patients (5.6+/-8.9 vs. 39.7+/-41.5 min), the actual discharge time was comparable. The median time for first passage of flatus was shorter in the EDA group than in the GA/PCA group (26 vs. 47 h). Nausea and vomiting were more common in the GA/PCA group than in the EDA group (16% vs. 28% and 11% vs. 22%, respectively), whereas hypotension (11% vs. 4%) and bradycardia (14% vs. 2%) were less frequent. Under the conditions of the present study, EDA with ropivacaine provided pain control after hip replacement superior to that provided by IV patient-controlled analgesia with morphine, particularly during the first 24 h. Both approaches to pain management were equally safe. IMPLICATIONS: Compared with general anesthesia and postoperative IV patient-controlled analgesia with morphine, epidural anesthesia and analgesia with the new local anesthetic ropivacaine enables patients to be discharged sooner from a postanesthesia care unit and provides superior pain relief during the first 24 h after hip replacement.     

Combination of intrathecal morphine and remifentanil infusion for fast-track anesthesia in off-pump coronary artery bypass surgery

OBJECTIVE: The purpose of this study was to assess the combination of intrathecal morphine and remifentanil infusion with isoflurane in off-pump coronary artery surgery, with a focus on postoperative analgesia and fast-tracking. DESIGN: Prospective, randomized, controlled, blinded clinical study. SETTING: University hospital. PARTICIPANTS: Forty-six patients who underwent elective off-pump coronary artery bypass grafting. INTERVENTIONS: Patients were randomly assigned to receive remifentanil infusion alone (control group, n = 23) or remifentanil infusion plus 10 microg/kg of intrathecal morphine (ITM group, n = 23). Induction and maintenance anesthesia were the same in both groups. Maintenance therapy was remifentanil infusion (0.25-1 microg/kg/min) and 0.5% to 1.5% isoflurane, with adjustments according to hemodynamics. After extubation, intravenous patient-controlled analgesia with morphine (1-mg bolus and 5-minute lockout) was administered, and Wilson sedation scores, visual analog pain scores (scale, 0-100 mm) at rest and during coughing, and cumulative morphine consumption were assessed at 1, 2, 4, 8, 12, 24, and 48 hours. Examiners were unaware of patients' group identities. Anesthetic recovery parameters and opioid-related, spinal anesthesia-related, and cardiac complications were recorded. MEASUREMENTS AND MAIN RESULTS: There were no differences between the groups' intraoperative hemodynamic or anesthetic recovery findings. Pain scores and morphine consumption were significantly lower in the ITM group at all time points after extubation (p = 0.0001-0.05). Group frequencies of opioid-related and cardiac complications were similar. No patient had central neuroaxial hematoma or post-spinal tap headache. CONCLUSION: In the setting of isoflurane anesthesia for off-pump coronary artery bypass grafting, ITM combined with remifentanil infusion provides better postoperative analgesia than does remifentanil infusion alone, and does not improve or negatively affect fast-tracking.     

A Comparison of Remifentanil and Morphine Sulfate for Acute Postoperative Analgesia after Total Intravenous Anesthesia with Remifentanil and Propofol

Background: The transition from remifentanil intraoperative anesthesia to postoperative analgesia must be planned carefully due to the short duration of action (3-10 min) of remifentanil hydrochloride, a potent, esterase-metabolized micro-opioid agonist. This study compared the efficacy and safety of transition regimens using remifentanil or morphine sulfate for immediate postoperative pain relief in patients who had surgery under general anesthesia with remifentanil/propofol.

Methods: One hundred fifty patients who had received open-label remifentanil and propofol for intraoperative anesthesia participated in this multicenter, double-blind, double-dummy study and were randomly assigned to either the remifentanil (R) group or the morphine sulfate (M) group. Twenty minutes before the anticipated end of surgery, the propofol infusion was decreased by 50%, and patients received either a placebo bolus (R group) or a bolus of 0.15 mg/kg morphine (M group). At the end of surgery, the propofol and remifentanil maintenance infusions were discontinued and the analgesic infusion was started: either 0.1 micro gram [center dot] kg sup -1 [center dot] min sup -1 remifentanil (R group) or placebo analgesic infusion (M group). During the 25 min after tracheal extubation, remifentanil titrations in increments of 0.025 micro gram [center dot] kg sup -1 [center dot] min sup -1 and placebo boluses (R group), or 2 mg intravenous morphine boluses and placebo rate increases (M group) were administered as necessary at 5-min intervals to control pain. Patients received the 0.075 mg/kg intravenous morphine bolus (R group) or placebo (M group) at 25 and 30 min after extubation, and the analgesic infusion was discontinued at 35 min. From 35 to 65 minutes after extubation, both groups received 2-6 mg open-label morphine analgesia every 5 min as needed.

Results: Successful analgesia, defined as no or mild pain with adequate respiration (respiratory rate [RR] >or= to 8 breaths/min and pulse oximetry >or= to 90%), was achieved in more patients in the R group than in the M group (58% vs. 33%, respectively) at 25 min after extubation (P < 0.05). The median remifentanil rate for successful analgesia was 0.125 micro gram [center dot] kg sup -1 [center dot] min sup -1 (range, 0.05-0.23 micro gram [center dot] kg sup -1 [center dot] min sup -1), and the median number of 2-mg morphine boluses used was 2 (range, 0-5 boluses). At 35 min after extubation, >or= to 74% of patients in both groups experienced moderate to severe pain. Median recovery times from the end of surgery were similar between groups. Transient respiratory depression, apnea, or both were the most frequent adverse events (14% for the R group vs. 6% for the M group; P > 0.05).     

The effect of nefopam on morphine overconsumption induced by large-dose remifentanil during propofol anesthesia for major abdominal surgery

Opioids may activate pain facilitatory systems opposing analgesia. We investigated whether large-dose remifentanil given during IV anesthesia caused postoperative morphine overconsumption and whether nefopam (a centrally acting analgesic) could reduce this. Sixty patients scheduled for abdominal surgery were included in this prospective, randomized study. The first 30 patients received either small-dose (Group S: 3 ng/mL) or large-dose (Group L: 8 ng/mL) remifentanil administrated by a target-controlled infusion during propofol anesthesia. Before skin closure, patients received morphine 0.15 mg/kg. Another 30 patients also received nefopam 20 mg intraoperatively. Postoperative pain was controlled by titration of morphine, followed by patient-controlled morphine analgesia (PCA). Morphine was requested earlier in Group L than in Group S (10 [1-63] min versus 37 [5-90] min, median [range]; P < 0.002). The dose of morphine by titration was larger in Group L than in Group S (0.28 [0.04-0.38] mg/kg versus 0.16 [0.03-0.41] mg/kg; P < 0.05). PCA morphine consumption and pain scores were similar. There were no differences between the nefopam groups in the time to first morphine request or in the dose of morphine by titration. Postoperative morphine overconsumption occurred after large-dose remifentanil and propofol anesthesia during the early postoperative period. Pretreatment with nefopam could be useful to prevent pain sensitization induced by opioids.     

Fast-track coronary artery bypass grafting surgery under general anesthesia with remifentanil and spinal analgesia with morphine and clonidine

OBJECTIVE: Effective postoperative analgesia is a critical part of fast-track cardiac surgery. This study compared the postoperative analgesic effect of fast-track anesthesia with remifentanil and spinal morphine and clonidine with that of sufentanil anesthesia followed by patient-controlled administration of intravenous morphine. DESIGN: Prospective, blinded, randomized study. SETTING: Single private institution. PARTICIPANTS: Forty patients selected for coronary artery bypass graft surgery allocated randomly into 2 groups. INTERVENTIONS: General anesthesia was performed with etomidate, isoflurane, cisatracurium, and either remifentanil (0.10-0.25 microg/kg/min) or sufentanil (up to 3.5 microg/kg). In the remifentanil group, patients received spinal morphine (4 microg/kg) and clonidine (1 microg/kg) before induction. Postoperatively, patients in both groups were connected to an intravenous patient-controlled analgesia (PCA) morphine pump that delivered a 1-g bolus with a 7-minute lockout interval. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated for pain on a visual analog scale (VAS), at rest and on deep breathing, and for intravenous PCA morphine consumption during 24 hours. The intravenous PCA morphine 24-hour cumulative dose was lower in the fast-track than in the control group (15.8+/-12.6 v 32.7+/-22.3 mg, p<0.05). Before extubation, VAS scores were higher in the fast-track group, but after they were lower both at rest and during deep breathing. Extubation delay was shorter in the fast-track group (156.5+/-46.1 v 272+/-116.4 minutes, p<0.05). CONCLUSION: The combination of anesthesia with remifentanil and spinal analgesia with morphine and clonidine produces effective analgesia after coronary artery surgery and a rapid extubation time.     

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.     

The analgesic efficacy of acetaminophen, ketoprofen, or their combination for pediatric surgical patients having soft tissue or orthopedic procedures

The combined use of acetaminophen and a nonsteroidal antiinflammatory drug has been shown to provide better postoperative analgesia than either drug alone in several adult studies. However, there are no pediatric studies analyzing similar effects when the currently recommended doses of acetaminophen are used. In a double-blind, placebo-controlled design we randomized 120 children, aged 1-9 yr, undergoing orthopedic or soft tissue surgery, into 3 groups to receive either acetaminophen 60 mg/kg rectally and 40 mg/kg orally, ketoprofen 2 mg/kg IV twice, or the combination of the active drugs. The first drug doses were given at anesthetic induction and the second doses 8 h thereafter. During anesthesia all children received sevoflurane and a continuous infusion of remifentanil. Postoperative pain was evaluated by the behavioral objective pain scale (0-9) for 24 h. The rescue medication was morphine 0.05 mg/kg IV. The primary outcome variable was morphine consumption. For statistical analysis, analysis of variance, chi2 test and Kaplan-Meier survival analysis were used. Morphine requirement was less in the combination than in the acetaminophen group both in the postanesthesia care unit (2.5 +/- 1.7 versus 3.9 +/- 2.1 morphine doses) and during the 24-h postoperative follow-up (4.1 +/- 2.5 versus 5.9 +/- 2.9 morphine doses) (P < 0.05). No differences existed between the ketoprofen and the acetaminophen groups. The objective pain scale scores were lowest in the combination group both in the postanesthesia care unit and in the postoperative ward (P < 0.05). When children were divided based on their surgery, opioid requirement and pain scores were less in the combination than in the parent drug groups only after orthopedic surgery. The combination of acetaminophen 100 mg/kg and ketoprofen 4 mg/kg in a day provided better analgesia and lower pain scores after orthopedic, but not soft tissue, surgery in children.     

Hemodynamics and emergence profile of remifentanil versus fentanyl prospectively compared in a large population of surgical patients

STUDY OBJECTIVE: To compare the responses to, and hemodynamics associated with surgical stress, recovery profiles, and anesthesiologists' satisfaction following balanced general anesthesia using either remifentanil or fentanyl in a large-scale population. DESIGN: Prospective, 1:1 single blind, randomized, controlled effectiveness study in which patients received either remifentanil or fentanyl in combination with a hypnotic-based anesthesia regimen of either isoflurane or propofol. SETTING: Multicenter study including 156 hospitals and ambulatory surgery facilities. PATIENTS: 2,438 patients (1,496 outpatients and 942 inpatients), 18 years of age or older, scheduled for elective surgeries under general endotracheal anesthesia, with an expected duration of unconsciousness > or =30 minutes. INTERVENTIONS: Patients were randomized to receive either intravenous (IV) remifentanil (0.5 microg/kg/min for induction and intubation, with the infusion rate decreased to 0.25 microg/kg/min after intubation) or IV fentanyl (administered according to anesthesiologists' usual practice) as the opioid during surgery. Concomitant hypnotic drugs were either propofol and/or isoflurane (with or without nitrous oxide) titrated according to protocol. Transition analgesia with either morphine or fentanyl was given to the remifentanil patients and, at the anesthesiologists' discretion, in the fentanyl patients. MEASUREMENTS: Vital signs, adverse events, and emergence profiles were assessed and recorded. Recovery profile was assessed by recording time spent in the postanesthesia care unit and step-down recovery unit, number and timing of adverse events, timing and dosage of rescue medications, and time to eligibility for discharge (to home or to hospital room). Anesthesiologists' satisfaction with the anesthetic regimen was assessed at the end of surgery. MAIN RESULTS: Remifentanil-treated patients exhibited lower systolic and diastolic blood pressures (by 10-15 mmHg) and lower heart rates (by 10-15 bpm) intraoperatively compared to the fentanyl-treated patients. This difference promptly disappeared on emergence. Remifentanil-treated patients responded to verbal command, left the operating room, and (for outpatients) were discharged home sooner than fentanyl-treated patients. Anesthesiologists rated the predictability of response to intraoperative titration, assessment of hemodynamic profiles, and the quality of anesthesia higher in the remifentanil-treated patients. CONCLUSIONS: This study confirms previous observations on the hemodynamic properties associated with remifentanil and extends these to a wider context than previously reported. These characteristics provide clinicians with an alternative in opioid-based anesthesia.     

Intraoperative infusion of dexmedetomidine reduces perioperative analgesic requirements

PURPOSE: This prospective, randomized, double-blind study was designed to assess whether intraoperative infusion of dexmedetomidine provides effective postoperative analgesia. Postoperative pain scores and morphine consumption were compared in a treated group and a placebo group, both of which received patient-controlled morphine after total abdominal hysterectomy. METHODS: Fifty women were randomly assigned to two groups. Group D (n = 25) received a loading dose of dexmedetomidine 1 mug.kg(-1) iv during induction of anesthesia, followed by a continuous infusion at a rate of 0.5 mug.kg(-1).hr(-1) throughout the operation. Group P (n = 25) received a volume-matched bolus and infusion of placebo (0.9% saline). For each case, heart rate, peripheral oxygen saturation, and systolic and diastolic blood pressure were recorded intraoperatively and for 48 hr postoperatively. Patients used a patient-controlled analgesia device to receive bolus doses of morphine after surgery. Total morphine consumption, pain scores, and sedation scores were recorded for the first 48 hr (two hours in the postanesthesia care unit and 46 hr on the ward). RESULTS: The groups were similar with respect to mean times to extubation of the trachea. Pain and sedation scores were also similar between groups at all corresponding times throughout the 48-hr period of observation. Group D patients consumed significantly less morphine in the postanesthesia care unit and on the ward (P < 0.05 and P < 0.01, respectively). Fewer patients in Group D experienced itching or nausea/vomiting (P < 0.05). CONCLUSION: Continuous iv dexmedetomidine during abdominal surgery provides effective postoperative analgesia, and reduces postoperative morphine requirements without increasing the incidence of side effects.     

Low-dose sufentanil dœs not potentiate intra-thecal morphine for perioperative analgesia after major colorectal surgery

PURPOSE: Both intrathecal sufentanil (ITS) and intrathecal morphine (ITM) improve analgesia in obstetrical or cardiac procedures. From a pharmacokinetic standpoint, combining these two opioids may improve perioperative analgesia. We performed a prospective randomized double-blind study to compare the analgesic efficacy of ITM alone vs a mixture of a low dose of ITS plus ITM for perioperative pain relief in colorectal surgery. METHODS: Eighty adult patients undergoing colorectal surgery were randomly allocated to receive either 0.4 mg ITM alone or 10 microg ITS plus 0.4 mg ITM before general anesthesia. Intraoperative intravenous sufentanil consumption, postoperative morphine consumption delivered with a patient controlled analgesia device, pain scores, patient satisfaction and adverse effects were recorded for the first 48 hr postoperatively. RESULTS: No differences were observed between groups with respect to intraoperative sufentanil consumption (39 +/- 23 microg in group ITM and 40 +/- 25 microg in group ITS plus ITM, P = 0.85) and in postoperative morphine consumption in postanesthesia care unit (6 +/- 5 mg vs 6 +/- 5 mg, P = 0.59), at 24 hr (26 +/- 17 vs 24 +/- 15 mg, P = 0.59) and at 48 hr (47 +/- 31 vs 44 +/- 22 mg, P = 0.58). Similarly, no differences were observed in regards to pain relief, patient satisfaction and incidence of adverse effects. CONCLUSIONS: These results do not support the addition of 10 microg ITS to 0.4 mg ITM for colorectal surgery, as low dose sufentanil does not improve intraoperative and postoperative analgesia in this setting.     

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.     

Analgesic Effect of Low-dose Intrathecal Morphine after Spinal Fusion in Children

Background: This study was designed to assess the postoperative analgesic effect of low-dose intrathecal morphine after scoliosis surgery in children.

Methods: Thirty children, 9-19 yr of age, scheduled for spinal fusion, were randomly allocated into three groups to receive a single dose of 0 (saline injection), 2, or 5 [mu]g/kg intrathecal morphine. After surgery, a patient-controlled analgesia device (PCA) provided free access to additional intravenous morphine. Children were monitored for 24 h in the postanesthesia care unit.

Results: The three groups were similar for age, weight, duration of surgery, and time to extubation. The time to first PCA demand was dose-dependently delayed by intrathecal morphine. The first 24 h of PCA morphine consumption was 49 +/- 17, 19 +/- 10, and 12 +/- 12 mg (mean +/- SD) in the saline, 2 [mu]g/kg morphine, and 5 [mu]g/kg morphine groups, respectively. Pain scores at rest were significantly lower over the whole study period after 2 and 5 [mu]g/kg intrathecal morphine than after saline, but there was no difference between intrathecal doses. Pain scores while coughing and the incidence of side effects were similar in the three groups.     

Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine

Background: Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that small-dose ketamine prevents this hyperalgesia.

Methods: Seventy-five patients undergoing major abdominal surgery were randomly assigned to receive (1) intraoperative remifentanil at 0.05 [mu]g [middle dot]kg-1 [middle dot]min-1 (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 (large-dose remifentanil); or (3) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 [mu]g [middle dot] kg-1 [middle dot] min-1 until skin closure and then 2 [mu]g [middle dot]kg-1 [middle dot]min-1 for 48 h (large-dose remifentanil-ketamine). Pain scores and morphine consumption were recorded for 48 postoperative hours. Quantitative sensory tests, peak expiratory flow measures, and cognitive tests were performed at 24 and 48 h.

Results: Hyperalgesia to von Frey hair stimulation adjacent to the surgical wound and morphine requirements were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P < 0.01) in the large-dose remifentanil group compared with the other two groups, which were comparable. There were no significant differences in pain, pressure pain detection threshold with an algometer, peak flow, cognitive tests, or side effects.     

Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy

Ketamine may prevent postoperative hyperalgesia. In patients undergoing arthroscopic meniscectomy using general anesthesia, we tested whether a single intraoperative dose of ketamine enhanced postoperative analgesia and improved functional outcome compared with a typical multimodal analgesic regimen. After the induction of anesthesia, 50 patients were randomly assigned to ketamine (0.15 mg/kg IV just after the induction of anesthesia) or a vehicle placebo. Standardized general anesthesia included propofol, alfentanil, and nitrous oxide. Bupivacaine (0.5%) and morphine (5 mg) were given intraarticularly at the end of surgery. Postoperative analgesia was initially provided with morphine and subsequently with naproxen sodium (550 mg orally twice daily) and Di-Antalvic (400 mg acetaminophen and 30 mg dextropropoxyphene) as needed. Pain scores, analgesic requirements, side effects, and ability to walk were assessed in the ambulatory unit and at home for three postoperative days. Times to awakening and to discharge were similar in the two groups. However, the Ketamine group had significantly less postoperative pain at rest and during mobilization on Days 0, 1, and 2. Furthermore, they consumed significantly fewer Di-Antalvic tablets than the control group (13 [7-17] vs 27 [16-32], median [25%-75% interquartile range]). Patients given ketamine were also able to walk for longer periods of time on the first postoperative day. In conclusion, adding small-dose ketamine to a multimodal analgesic regimen improved postoperative analgesia and functional outcome after outpatient knee arthroscopy.     

Preoperative oral dextromethorphan does not reduce pain or analgesic consumption in children after adenotonsillectomy

In this randomized, double-blinded, placebo-controlled, prospective study, we evaluated the analgesic efficacy of dextromethorphan 0.5 mg/kg or 1.0 mg/kg p.o. 1 h before adenotonsillectomy in 57 children 6-12 yr of age. Anesthetic management was standardized. Morphine 0.075 mg/kg i.v. and acetaminophen 25-35 mg/kg p.r. were administered after anesthetic induction but before the start of surgery. A 4-point behavioral score (1 = asleep, 2 = awake and calm, 3 = awake and crying, 4 = thrashing) was recorded on admission to and discharge from the postanesthesia care unit (PACU). In the PACU, pain was assessed with Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and recorded every 15 min until the patient was transferred to the day surgery unit (DSU). In the DSU, patients rated their pain using a 10-cm baseline 0-10 visual analog pain scale (VAS) every 30 min until they were discharged home. A 24-h VAS was obtained by phone interview, and parental satisfaction was scored (yes/no) regarding their child's postoperative analgesia. Morphine 0.025 mg/kg i.v. was administered to children with CHEOPS score >6, who verbalized pain, or who were crying in any consecutive 5-min observation periods in the PACU. Total morphine consumption was recorded. The study groups were comparable with respect to demographic variables. We were unable to detect any differences between study groups with respect to postoperative morphine consumption, CHEOPS, behavior scores, VAS, or parental satisfaction. Implications: Premedication with dextromethorphan 0.5 or 1.0 mg/kg p.o. does not improve postoperative analgesia in school-aged children who receive preemptive morphine 0.075 mg/kg i.v. and acetaminophen 25-35 mg/kg p.r. during nitrous oxide and desflurane anesthesia for adenotonsillectomy.     

Remifentanil infusion for cleft palate surgery in young infants

BACKGROUND: The residual depressant effect of opioid is a major concern in infants scheduled for cleft palate repair. Remifentanil is associated with a fast and predictable recovery, independent of age. METHODS: About 40 infants in the 2-12 month age range were prospectively enrolled in this open study, to receive either remifentanil (infusion starting at 0.25 microg x kg(-1) x min(-1)) or sufentanil as part of a balanced anaesthesia regimen. Isoflurane was maintained at an endtidal concentration of 1.2% in oxygen and nitrous oxide and the opioid dosing was titrated to autonomic responses. Postoperative pain relief was provided by morphine infusion. Morphine administration started intraoperatively in the remifentanil group. RESULTS: Consistent haemodynamic stability was achieved throughout surgery in both groups. Infants of the remifentanil group required, on average, lower concentrations of isoflurane than children of the sufentanil group (1.2 +/- 0.2% vs 1.7 +/- 0.3%, P < 0.001). The median time from last suture to tracheal extubation was 12.5 min (5-25 min) in the remifentanil group and 15.0 min (10-30 min) in the sufentanil group. There was no evidence of hyperalgesia or enhanced morphine consumption in the remifentanil group compared with the sufentanil group. Postoperative pain scores were even lower in the remifentanil group, compared with the sufentanil group, soon after arrival in the postanaesthesia care unit. CONCLUSIONS: Remifentanil-based anaesthesia appeared well suited for primary cleft palate repair in young infants.