Postoperative pain management with intravenous patient-controlled morphine: comparison of the effect of adding magnesium or ketamine

BACKGROUND AND OBJECTIVE: This double-blind randomized study tested whether the addition of magnesium or ketamine to morphine for intravenous patient-controlled analgesia resulted in improved analgesic efficacy and lower pain scores compared with morphine patient-controlled analgesia alone after major abdominal surgery. METHOD: Ninety patients (3 x 30) were randomly allocated to receive either morphine 0.4 mg mL(-1) (Group M) by patient-controlled analgesia, morphine 0.4mg mL(-1) + MgSO4 30mg mL(-1) (Group MM) or morphine 0.4 mg mL(-1) + ketamine 1 mg mL(-1) (Group MK). Postoperative analgesia was started when the verbal rating scale was > or = 2. Patients were first given a standardized loading dose (0.05 mg kg(-1)) of the study solution. They were then allowed to use bolus doses of this solution (0.0125 mg kg(-1) every 20 min without time limit). Discomfort, sedation, pain scores, cumulative morphine consumption and adverse effects were recorded up to 24 h after the start of the patient-controlled analgesia. RESULTS: The level of discomfort, level of sedation and verbal rating scores decreased significantly with time in all groups (P < 0.05). Both verbal rating and discomfort scores were significantly lower in Groups MM and MK at 15, 30 and 60 min compared with Group M (P < 0.001). Cumulative morphine consumption after 12 and 24 h was significantly higher in Group M alone (median 26 and 49 mg, respectively) compared with Group MM (24.2 and 45.7 mg) and Group MK (24.4 and 46.5 mg). CONCLUSIONS: In the immediate postoperative period, the addition of magnesium or ketamine to morphine for intravenous patient-controlled analgesia led to a significantly lower consumption of morphine. However, these differences are unlikely to be of any clinical relevance.     

Effect of i.v. ketamine in combination with epidural bupivacaine or epidural morphine on postoperative pain and wound tenderness after renal surgery

We studied 60 patients undergoing operation on the kidney with combined general and epidural anaesthesia, in a double-blind, randomized, controlled study. Patients were allocated to receive a preoperative bolus dose of ketamine 10 mg i.v., followed by an i.v. infusion of ketamine 10 mg h-1 for 48 h after operation, or placebo. During the first 24 h after surgery, all patients received 4 ml h-1 of epidural bupivacaine 2.5 mg ml-1. From 24 to 48 h after operation, patients received epidural morphine 0.2 mg h-1 preceded by a bolus dose of 2 mg. In addition, patient-controlled analgesia (PCA) with i.v. morphine (2.5 mg, lockout time 15 min) was offered from 0 to 48 h after operation. Patients who received ketamine felt significantly more sedated at 0-24 h, but not at 24-48 h after operation, compared with patients who received placebo (P = 0.002 and P = 0.127, respectively). There were no significant differences in pain (VAS) at rest, during mobilization or cough, PCA morphine consumption, sensory block to pinprick, pressure pain detection threshold assessed with an algometer, touch and pain detection thresholds assessed with von Frey hairs, peak flow or side effects other than sedation. The power of detecting a reduction in VAS scores of 20 mm in our study was 80% at the 5% significance level. We conclude that we were unable to demonstrate an (additive) analgesic or opioid sparing effect of ketamine 10 mg h-1 i.v. combined with epidural bupivacaine at 0-24 h, or epidural morphine at 24-48 h after renal surgery.      

Evaluation of the safety and efficacy of epidural ketamine combined with morphine for postoperative analgesia after major upper abdominal surgery

STUDY OBJECTIVE: To evaluate the efficacy of the combination of epidural ketamine and morphine compared with epidural morphine alone for postoperative pain relief following major upper abdominal surgery. STUDY DESIGN: Prospective, randomized, double-blinded study. SETTING: Tertiary care referral and teaching hospital. PATIENTS: 46 ASA physical status I and II patients who underwent major upper abdominal procedures. INTERVENTIONS: Patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg whereas patients in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine postoperatively. MEASUREMENTS: A blinded observer using a visual analog scale (VAS) for pain assessment followed up patients for 48 hours postoperatively. Top-up dose of epidural morphine was provided when VAS was higher than 4. Analgesic requirements and side effects were compared between the two groups. RESULTS: Only 40 patients completed the study. There were no differences between the two groups with respect to age, gender, weight, duration, or type of surgical procedure or intraoperative opioid requirements. Onset of analgesia was faster (p < 0.001) in Group 2 (11 min) than in Group 1 patients (25 min). The time for first requirement of analgesia was significantly (p < 0.01) longer (19.8 +/- 9.8 hours) in Group 2 patients than Group 1 (12.8 +/- 6.2 hours). Total number of supplemental doses of epidural morphine required in the first 48 hours postoperatively was also significantly less (p < 0.005) in Group 2 compared to Group 1. Patients in Group 2 had higher sedation scores than Group I patients for the first 2 hours postoperatively. None of the patients in either group developed hallucinations or respiratory depression. Other side effects such as pruritus, nausea, and vomiting were also similar in both groups. CONCLUSIONS: The addition of epidural ketamine 1 mg/kg to morphine 50 microg/kg improved analgesia after major upper abdominal surgery without increasing side effects.     

Patient-controlled epidural analgesia with morphine or morphine plus ketamine for post-operative pain relief

Sixty patients were randomly assigned to two equal groups. Group I received epidural morphine 1 mg after surgery and used a patient-controlled analgesia device programmed to deliver morphine 0. 2 mg h-1, 0.2 mg per bolus. Group II received an epidural loading dose of morphine 1 mg plus ketamine 5 mg and used a patient-controlled analgesia device programmed to deliver morphine 0. 2 mg+ketamine 0.5 mg h-1, morphine 0.2 mg+ketamine 0.5 mg per bolus with a lockout time of 10 min. The mean morphine consumption was 8. 6+/-0.7 mg for group I and 6.2+/-0.2 mg for group II. Although group II utilized significantly less morphine (P < 0.05), pain relief was significantly better in group II than in group I (P < 0.05) in the first 3 h. Vomiting occurred more frequently in group I (26%) than in group II (13%). The frequency and severity of pruritus and level of sedation were similar in the two groups. These findings suggest that patient-controlled epidural analgesia with morphine plus ketamine may provide effective analgesia with a lesser dose of morphine and fewer subsequent side effects, compared with patient-controlled epidural analgesia with morphine alone after lower abdominal surgery.     

The benefits of intraoperative small-dose ketamine on postoperative pain after anterior cruciate ligament repair

In a randomized, double-blinded study with three parallel groups, we assessed the analgesic effect of intraoperative ketamine administration in 45 ASA physical status I or II patients undergoing elective arthroscopic anterior ligament repair under general anesthesia. The patients received either IV ketamine 0.15 mg/kg after the induction of anesthesia and before surgical incision and normal saline at the end of surgery (PRE group); normal saline after the induction of anesthesia and before surgical incision and IV ketamine at the end of surgery (POST group); or normal saline at the beginning and the end of surgery (CONT group). Anesthesia was performed with propofol (2 mg/kg for induction, 60-200 microg x kg(-1) x min(-1) for maintenance), sufentanil (0.2 microg/kg 10 min after surgical incision, followed by an infusion of 0.25 microg x kg(-1) x h(-1) stopped 30 min before skinclosure), vecuronium (0.1 mg/kg), and 60% N2O in O2 via a laryngeal mask airway. Postoperative analgesia was initially provided with IV morphine in the postanesthesia care unit, then with IV patient-controlled analgesia started before discharge from the postanesthesia care unit. Pain scores, morphine consumption, side effects, and degree of knee flexion were recorded over 48 h and during the first and second physiotherapy periods, performed on Days 1 and 2. Patients in the ketamine groups required significantly less morphine than those in the CONT group over 48 h postoperatively (CONT group 67.7+/-38.3 mg versus PRE group 34.3+/-23.2 mg and POST group 29.5+/-21.5 mg; P < 0.01). Better first knee flexion (CONT group 35+/-10 degrees versus PRE group 46+/-12 degrees and POST group 47+/-13 degrees; P < 0.05) and lower morphine consumption (CONT group 3.8+/-1.7 mg versus PRE group 1.2+/-0.4 mg and POST group 1.4+/-0.4 mg; P < 0.05) were noted at first knee mobilization. No differences were seen between the PRE and POST groups, except for an increase in morphine demand in the PRE versus the POST group (P < 0.05) in the second hour postoperatively. IMPLICATIONS: We found that intraoperative small-dose ketamine reduced postoperative morphine requirements and improved mobilization 24 h after arthroscopic anterior ligament repair. No differences were observed in the timing of administration. Intraoperative small-dose ketamine may therefore be a useful adjuvant to perioperative analgesic management.     

Awake nasotracheal fiberoptic intubation: patient comfort,intubating conditions,and hemodynamic stability during conscious sedation with remifentanil

Awake nasotracheal fiberoptic intubation requires an anesthetic management that provides sufficient patient comfort, adequate intubating conditions, and stable hemodynamics. Short-acting and easily titratable analgesics are excellent choices for this maneuver. In this study, our aim was to determine an appropriate dosage regimen of remifentanil for awake nasotracheal fiberoptic intubation. For that reason, we compared two different dosage regimens. Twenty-four patients were randomly assigned to receive remifentanil 0.75 micro g/kg in bolus, followed by a continuous infusion of 0.075 micro g x kg(-1) x min(-1) (Group L), or remifentanil 1.5 micro g/kg in bolus, followed by a continuous infusion of 0.15 micro g x kg(-1) x min(-1) (Group H). All patients were premedicated with midazolam 0.05 mg/kg IV and glycopyrrolate 0.2 mg IV. Both dosage regimens ensured patient comfort and sedation. Discomfort did not differ between groups. Patients in Group H were sedated more profoundly. Hemodynamic stability was maintained with both remifentanil doses. Intubating conditions were adequate in all patients and comparable between the groups. The large dosage regimen did not result in any additional benefit compared with the small dosage. For awake nasotracheal fiberoptic intubation, we therefore recommend remifentanil 0.75 micro g/kg in bolus followed by continuous infusion of 0.075 micro g x kg(-1) x min(-1), supplemented with midazolam 0.05 mg/kg.     

Preoperative epidural ketamine in combination with morphine does not have a clinically relevant intra- and postoperative opioid-sparing effect

In this prospective, randomized, and double-blinded clinical trial, we evaluated the efficacy of preincisional administration of epidural ketamine with morphine compared with epidural morphine alone for postoperative pain relief after major upper-abdominal surgery. We studied 50 ASA I and II patients undergoing major upper-abdominal procedures. These patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg, whereas those in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine 30 min before incision. Intraoperative analgesia was provided in addition, with IV morphine, and the requirement was noted. A blinded observer using a visual analog scale for pain assessment observed patients for 48 h after surgery. Additional doses of epidural morphine were provided when the visual analog scale score was more than 4. Analgesic requirements and side effects were compared between the two groups. There were no differences between the two groups with respect to age, sex, weight, or duration or type of the surgical procedures. The intraoperative morphine requirement was significantly (P = 0.018) less in Group 2 patients (median, 6.8 mg; range, 3-15 mg) compared with patients in Group 1 (median, 8.3 mg; range, 4.5-15 mg). The time for the first requirement of analgesia was significantly (P = 0.021) longer (median, 17 h; range, 10-48 h) in Group 2 patients than in Group 1 (median, 12 h; range, 4-36 h). The total number of supplemental doses of epidural morphine required in the first 48 h after surgery was comparable (P = 0.1977) in both groups. Sedation scores were similar in both groups. One patient in Group 2 developed hallucinations after study drug administration. None of the patients in either group developed respiratory depression. Other side effects, such as pruritus, nausea, and vomiting, were also similar in both groups. Although the addition of ketamine had synergistic analgesic effects with morphine (reduced intraoperative morphine consumption and prolonged time for first requirement of analgesia), there was no long- lasting preemptive benefit seen with this combination (in terms of reduction in supplemental analgesia) for patients undergoing major upper-abdominal procedures. IMPLICATIONS: Ketamine added to epidural morphine given before surgery can decrease postoperative pain by its preemptive effect, opioid potentiation, and prevention of acute opioid tolerance. A single epidural bolus of 1 mg/kg of ketamine with morphine given before major upper-abdominal surgery did not result in a clinically relevant reduction in postoperative pain relief.     

Ketamine does not decrease postoperative pain after remifentanil-based anaesthesia for tonsillectomy in adults

BACKGROUND: There are conflicting results concerning the pre-emptive effect of ketamine on central sensitization following surgery. The aim of this prospective, randomized, double-blind, placebo-controlled study was to assess the effect of the N-methyl-D-aspartate receptor antagonist ketamine on postoperative morphine consumption and pain score after remifentanil-based anaesthesia in adult patients scheduled for tonsillectomy. METHODS: We studied 40 adult patients undergoing elective tonsillectomy. Total intravenous anaesthesia was induced and maintained with remifentanil (0.125-1.0 microg kg(-1) min(-1)) and propofol target-controlled infusion. Patients in group K received a bolus dose of ketamine 0.5 mg kg(-1) immediately after anaesthetic induction, followed by a continuous infusion of 2 microg kg(-1) min(-1). Saline was administered in the same sequence in group S. Propofol, remifentanil, and the study drug infusions were discontinued at the end of surgery. RESULTS: Intraoperative remifentanil consumption (0.57 +/- 0.18 in group K vs. 0.55 +/- 0.14 microg kg(-1) min(-1) in group S), morphine requirement in the PACU (11 +/- 3 in group K vs. 9 +/- 4 mg in group S) and in the ward (22 +/- 11 in group K vs. 25 +/- 14 mg in group S), median time to first analgesia in the ward (338 +/- 126 in group K vs. 328 +/- 144 min in group S), and VAS pain scores were comparable in both groups. CONCLUSION: Small-dose of ketamine does not seem to be a useful adjunct to remifentanil-based anaesthesia during short, painful surgical procedures.     

Perioperative small-dose S(+)-ketamine has no incremental beneficial effects on postoperative pain when standard-practice opioid infusions are used

Several studies report that when small-dose racemic ketamine, an N-methyl-D-aspartate receptor antagonist, is administered perioperatively, opioid consumption is reduced postoperatively. S(+)-ketamine has a higher affinity for the N-methyl-D-aspartate receptor and less-serious side effects than racemic ketamine. Thirty patients scheduled for elective arthroscopic anterior cruciate ligament repair were enrolled in this randomized, double-blinded clinical trial designed to determine the preemptive effect of S(+)-ketamine on postoperative analgesia requirements in a setting of clinically relevant perioperative analgesia. Total IV anesthesia was induced and maintained with remifentanil (0.125-1.0 microg x kg(-1) x min(-1)) and a propofol target-controlled infusion (target 2-4 microg/mL). The Ketamine group received a bolus of 0.5 mg/kg S(+)-ketamine before incision, followed by a continuing infusion of 2 microg x kg(-1) x min(-1) until 2 h after emergence from anesthesia. The Control group received NaCl in the same sequence. After IV morphine provided pain relief down to < or =3 on a visual analog scale scored from 0 to 10, patients were connected to a patient-controlled analgesia device. There were no significant differences between the two groups in terms of total morphine consumption or VAS scores, either at rest or with movement. In our study, S(+)-ketamine did not contribute to postoperative pain reduction, possibly because of the clinically routine perioperative opioid analgesia. IMPLICATIONS: Small-dose S(+)-ketamine had no positive effect on postoperative analgesia when administered perioperatively for elective arthroscopic anterior cruciate ligament repair. Unlike investigations of the racemic mixture of ketamine, our study methods included timely standard-practice perioperative opioid analgesia, which seems to make supplemental analgesia unnecessary.     

Pre-incisional epidural ketamine, morphine and bupivacaine combined with epidural and general anaesthesia provides pre-emptive analgesia for upper abdominal surgery

BACKGROUND: Previous studies have shown that N-methyl-D-asparate (NMDA) receptor antagonists provide a pre-emptive analgesic effect in humans. This study investigated the benefits of pre-emptive analgesia for upper abdominal surgery, using pre-incisional epidural ketamine + morphine + bupivacaine (K+M+B) treatment for achieving postoperative pain relief. METHODS: Sixty ASA 1-2 patients scheduled for upper abdominal surgery were allocated to three groups in a randomized, single-blinded study. Patients in the control group (I) received general anaesthesia followed by an infusion of normal saline. Group II and III patients received general anaesthesia with a continuous epidural infusion of 2% lidocaine. Thirty minutes after the incision in groups I and II, an epidural pain control regimen was administered using ketamine (10 mg) and morphine (1 mg) in 10 ml of 0.085% bupivacaine (K+M+B). Group III patients also received K+M+B, but it was administered 10 min after the 2% lidocaine injection and 30 min before skin incision. All patients received an epidural pain control regimen (q12 h) for 3 days after their first injection. Patient-controlled analgesia (PCA) with morphine was used to control subsequent postoperative pain. During the 3-day period following surgery, duration to PCA trigger (h), morphine consumption (mg), pain intensity at rest and when coughing/moving, and analgesic-related adverse effects were recorded. The VAS scale (0-10) was used to assess pain intensity. RESULTS: Median times to first PCA trigger were 1.2 (0.5-2.0) h, 3.0 (0.7-4.2) h, and 4.0 (2.5-7.5) h for groups I, II, and III, respectively. Both the incident and resting pain scores were consistently lower for group III patients than groups I and II. The number of PCA triggers (all attempts/successful triggers) during the day following surgery were 14.0 (3-30)/8.0 (3-24) times, 10.0 (3-23)/6.0 (2-20) times, and 7.0 (3-12)/4.5 (1-10) times for groups I, II, and III. Total morphine consumption for the 3-day observation period was 12.5 (3-42) mg, 10.5 (2-29) mg, and 6.0 (1-20) for groups I, II, and III, respectively. CONCLUSION: Pre-incisional epidural K+M+B treatment combined with continuous epidural anaesthesia and general anaesthesia provides an ideal pre-emptive analgesic therapy, exhibiting better postoperative pain relief than general anaesthesia and post-incisional K+M+B treatment.     

The use of midazolam and small-dose ketamine for sedation and analgesia during local anesthesia.

Small-dose ketamine in combination with sedative drugs has increasingly been used for sedation and analgesia in local anesthesia. We compared the clinical efficacy of midazolam with two different ketamine infusion regimens during plastic surgery under local anesthesia. Sixty patients undergoing plastic surgery procedures with local anesthesia were randomly assigned to two groups of 30 patients each in a double-blinded fashion. All patients received a bolus of 0.05 mg/kg midazolam, followed by a stepwise infusion: 1.67 microg x kg(-1) x min(-1) for the first 30 min, then reduced to 1.33 microg x kg(-1) x min(-1) for 90 min and subsequently to 1 microg x kg(-1) x min(-1). Two minutes before the infiltration of local anesthetic solution, a bolus of ketamine 0.3 mg/kg IV was administered, followed by a stepwise infusion of ketamine: Group A, 16.67 microg x kg(-1) x min(-1) for 30 min, 13.3 microg x kg(-1) x min(-1) for 90 min, and subsequently 10 microg x kg(-1) x min(-1); Group B, 8.33 microg x kg(-1) x min(-1) for 30 min, 6.67 microg x kg(-1) x min(-1) for 90 min, and then 5 microg x kg(-1) x min(-1). The level of sedation was evaluated by using the modified Observer's Assessment of Alertness/Sedation scale. We observed the effects of the two ketamine infusion regimens on sedation levels, respiratory and cardiovascular variables, and perioperative side effects. In both groups, midazolam and ketamine produced adequate sedation (with Observer's Assessment of Alertness/Sedation scores of 2-4) without significant respiratory and cardiovascular depression during surgery. However, there were fewer disruptive movements and there was less postoperative vomiting in Group B (P < 0.01). In conclusion, ketamine and midazolam provided satisfactory intraoperative sedation, analgesia, and amnesia in both groups. However, side effects associated with ketamine occurred less often in the smaller-dose ketamine group. IMPLICATIONS: Sedation and analgesia are often provided during local anesthesia. This study demonstrates that a small-dose ketamine infusion in combination with midazolam provided satisfactory intraoperative sedation, analgesia, and amnesia in healthy plastic-surgery patients when it was used to supplement local anesthesia.     

Small-dose ketamine infusion improves postoperative analgesia and rehabilitation after total knee arthroplasty

We designed this study to evaluate the effect of small-dose IV ketamine in combination with continuous femoral nerve block on postoperative pain and rehabilitation after total knee arthroplasty. Continuous femoral nerve block was started with 0.3 mL/kg of 0.75% ropivacaine before surgery and continued in the surgical ward for 48 h with 0.2% ropivacaine at a rate of 0.1 mL . kg(-1) . h(-1). Patients were randomly assigned to receive an initial bolus of 0.5 mg/kg ketamine followed by a continuous infusion of 3 mug . kg(-1) . min(-1) during surgery and 1.5 mug . kg(-1) . min(-1) for 48 h (ketamine group) or an equal volume of saline (control group). Additional postoperative analgesia was provided by patient-controlled IV morphine. Pain scores and morphine consumption were recorded over 48 h. The maximal degree of active knee flexion tolerated was recorded daily until hospital discharge. Follow-up was performed 6 wk and 3 mo after surgery. The ketamine group required significantly less morphine than the control group (45 +/- 20 mg versus 69 +/- 30 mg; P < 0.02). Patients in the ketamine group reached 90 degrees of active knee flexion more rapidly than those in the control group (at 7 [5-11] versus 12 [8-45] days, median [25%-75% interquartile range]; P < 0.03). Outcomes at 6 wk and 3 mo were similar in each group. These results confirm that ketamine is a useful analgesic adjuvant in perioperative multimodal analgesia with a positive impact on early knee mobilization. No patient in either group reported sedation, hallucinations, nightmares, or diplopia, and no differences were noted in the incidence of nausea and vomiting between the two groups.     

Postoperative extradural analgesia with morphine and ropivacaine. A double-blind comparison between placebo and ropivacaine 10 mg/h or 16 mg/h

BACKGROUND: Some controversy exists in the literature on the benefit of epidurals compared to patient-controlled intravenous analgesia (PCA). Also, the dose of ropivacaine for epidural analgesia when combined with morphine remains uncertain. The aim of this study was to compare the epidural vs. PCA technique and high-dose vs. low-dose ropivacaine combined with morphine during knee replacement surgery. METHODS: In this prospective, randomized, double-blind study, postoperative pain relief with a combination of epidural ropivacaine (Group L: 10 mg h-1, Group H: 16 mg h-1) and morphine (0.16 mg h-1) was evaluated in 30 patients. A placebo group (Group PL) of 15 patients having PCA morphine served as the control. Visual analog pain (VAS), morphine consumption, sensory and motor block and side-effects were recorded during 48 h. RESULTS: VAS scores at rest were significantly lower in Groups L and H compared to Group PL. On movement, Group H had lower VAS scores than Group PL during 3-27 h (P<0.05) and Group L during 4-9 h (P<0.05), while Group L had lower a VAS than Group PL during 9-18 h (P<0.05). Morphine consumption after 48 h was greater in Group PL (64.6+/-36.3 mg) vs. Group L (23.3+/-33.9 mg) (P<0.001) and Group H (4.3+/-9.6 mg) (P<0.0001). Mild motor block was seen in Group H in 20% and 14% patients at 24 h and 48 h, respectively, but time to mobilization was similar between the groups. Pruritus was more common in the ropivacaine groups (P<0.05). CONCLUSION: Lumbar epidural analgesia using a combination of ropivacaine (16 mg h-1) and morphine (0.16 mg h-1) provides superior analgesia compared to the PCA technique or ropivacaine (10 mg h-1) and morphine (0.16 mg h-1). Although this resulted in a mild motor block during the first 12 h, patient mobilization was similar in all groups.     

The influence of preemptive spinal anesthesia on postoperative pain

STUDY OBJECTIVE: To examine the influence of spinal anesthesia on postoperative pain and postoperative opioid requirements. DESIGN: Prospective randomized study. SETTING: Bnai-Zion Medical Center, Haifa, Israel-a government hospital. MEASUREMENTS AND MAIN RESULTS: 30 ASA physical status I and II unpremedicated women undergoing elective total abdominal hysterectomy were randomly allocated into two groups of 15 patients each using a sealed envelope technique. Patients in Group 1 were given a subarachnoid injection of 12 mg hyperbaric bupivacaine and after 10 minutes general anesthesia was induced. Patients in Group 2 received only general anesthesia. Anesthesia was induced with midazolam and maintained with oxygen, N2O, isoflurane, and pancuronium. No opioids were given intraoperatively. Postoperatively patient-controlled analgesia (PCA) with morphine was initiated in both groups (1 mg x mL(-1), bolus dose 1 mg, lockout interval 10 minutes, and background infusion 1 mg x mL(-1)) at patient first request for analgesic. Pain was assessed over 24 hours by cumulative morphine dose and visual analog score (VAS). Postoperative PCA morphine consumption at 2, 6, and 24 hours following patient first request for analgesic for Groups 1 and 2 were: 3.1 +/- 1 mg versus 7.2 +/- 3 mg (p = 0.04), 13.4 +/- 2 mg versus 17.2 +/- 4 mg (p = 0.03) and 35.9 +/- 8 mg versus 47.7 +/- 8 mg in Group 2 (p = 0.04). VAS scores at 4, 6, 12, and 24 hours postoperatively were not significantly different between the two groups. CONCLUSIONS: Preoperative neural blockade may reduce postoperative analgesic requirements.     

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 microg x kg(-1) x min(-1) (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 microg x kg(-1) x min(-1) (large-dose remifentanil); or (3) intraoperative remifentanil at 0.40 microg x kg(-1) x min(-1) and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 microg x kg(-1) x min(-1) until skin closure and then 2 microg x kg(-1) x 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. CONCLUSION: A relatively large dose of intraoperative remifentanil triggers postoperative secondary hyperalgesia. Remifentanil-induced hyperalgesia was prevented by small-dose ketamine, implicating an N-methyl-d-aspartate pain-facilitator process.     

The influence of timing of systemic ketamine administration on postoperative morphine consumption

STUDY OBJECTIVE: To determine the influence of timing of systemic ketamine administration on postoperative morphine consumption. DESIGN: Prospective randomized study. SETTING: Operating rooms, postanesthesia care unit, and gynecology service of a university hospital. PATIENTS: Forty-five patients undergoing laparotomy for benign gynecologic pathologies were randomized into 3 groups. INTERVENTIONS: In Group 1, before surgical incision, patients received 0.5 mg/kg ketamine IV, followed by normal saline infusion and normal saline IV at wound closure in group 1 (n = 15). In group 2 (n = 15), patients received 0.5 mg/kg ketamine IV before surgery, followed by ketamine infusion 600 mug . kg(-1) . h(-1), until wound closure and normal saline IV at that time. In the other group (group 3, n = 15), patients received normal saline IV before surgery, followed by saline infusion and then 0.5 mg/kg ketamine IV at wound closure. In the postoperative period, patient-controlled analgesia IV morphine was used for postoperative pain relief. First requested analgesic medication time was recorded. Postoperative pain was assessed by measuring morphine consumption at 0 to 2, 0 to 4, and 0 to 24 hours and visual analog scale (VAS) pain scores in response to cough at 2nd, 4th, and 24th hours and during rest at 0 to 2, 0 to 4, and 0 to 24 hours after surgery. MEASUREMENT AND MAIN RESULTS: First requested analgesia was shorter in group 1 than the others (P < .01). Mean VAS pain scores in response to cough at 24th hour in groups 2 and 3 were significantly lower than in group 1 (P < .001 and P < .01, respectively). Mean VAS pain scores during rest at 0 to 24 hours in groups 2 and 3 were significantly lower than in group 1 (P < .01 and P < .05, respectively). Morphine consumption was lower in groups 2 and 3 at 0 to 2 hours (P < .001 and P < .01). Moreover, morphine consumption at 0 to 4 hours in group 2 was significantly lower (P < .01). CONCLUSIONS: Lower pain scores and morphine consumption in groups 2 and 3 may be related to higher plasma ketamine concentrations caused by the higher doses and later administration. Our findings suggest that a single preoperative dose of ketamine provided less analgesia compared with other dosing regimens that included intraoperative infusions or postoperative administration.     

Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind trial

BACKGROUND: Preliminary clinical studies have suggested that gabapentin may produce analgesia and reduce the need for opioids in postoperative patients. The aim of the present study was to investigate the opioid-sparing and analgesic effects of gabapentin administered during the first 24 h after abdominal hysterectomy. METHODS: In a randomized, double-blind study, 80 patients received oral gabapentin 1200 mg or placebo 1 h before surgery, followed by oral gabapentin 600 mg or placebo 8, 16 and 24 h after the initial dose. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 24 h postoperatively. Pain was assessed on a visual analogue scale (VAS) at rest and during mobilization, nausea, somnolence and dizziness on a four-point verbal scale, and vomiting as present/not present at 2, 4, 22 and 24 h postoperatively. RESULTS: Thirty-nine patients in the gabapentin group, and 32 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from median 63 (interquartile range 53-88) mg to 43 (28-60) mg (P < 0.001). We observed a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0 to 2 h, and from 0 to 4 h postoperatively (R2 = 0.30, P = 0.003 and R2 = 0.24 P = 0.008, respectively). No significant differences in pain at rest or during mobilization, or in side-effects, were observed between groups. CONCLUSION: Gabapentin in a total dose of 3000 mg, administered before and during the first 24 h after abdominal hysterectomy, reduced morphine consumption with 32%, without significant effects on pain scores. No significant differences in side-effects were observed between study-groups.     

Dexmedetomidine in combination with morphine PCA provides superior analgesia for shockwave lithotripsy

PURPOSE: To compare the analgesic effects of dexmedetomidine/morphine with those of tramadol/midazolam in patients undergoing extracorporeal shockwave lithotripsy (ESWL) for urinary calculi. METHODS: Sixty patients were randomized to receive either dexmedetomidine 1 micro g*kg(-1) iv followed by 0.5 micro g*kg(-1)*hr(-1) infusion together with morphine patient-controlled analgesia [(PCA); 2 mg bolus, five minutes lockout, 2 mg*hr(-1) infusion; (Group DEX)], or tramadol 1.5 mg*kg(-1) pre-mixed with midazolam 30 micro g*kg(-1) iv followed by tramadol PCA [20 mg bolus, five minute lockout, 20 mg*hr(-1) infusion; (Group TRA)]. Pain was assessed at baseline and every 15 min thereafter. Patients' and urologist's satisfaction with analgesia and sedation were determined on a seven-point scale ranging from 1 (extremely dissatisfied) to 7 (extremely satisfied). Patient's discharge time was also documented. RESULTS: Visual analogue scale scores over time were consistently lower in Group DEX compared with Group TRA (P = 0.001). Patients' satisfaction with analgesia (5 +/- 1 vs 4 +/- 2, P = 0.012) and with sedation (6 +/- 1 vs 5 +/- 1, P = 0.020), and urologist's satisfaction (6 +/- 1 vs 4 +/- 2, P = 0.001) were all higher amongst Group DEX patients compared with Group TRA. There was no difference between discharge times of patients in Group DEX compared with those in Group TRA [85 (60,115) min vs 65 (40,95) min, P = 0.069]. CONCLUSION: Dexmedetomidine in combination with morphine PCA provided better analgesia for ESWL and was associated with higher patients' and urologist's satisfaction when compared with a tramadol/midazolam PCA combination.     

Supplementing desflurane-remifentanil anesthesia with small-dose ketamine reduces perioperative opioid analgesic requirements

Relative large-dose intraoperative remifentanil could lead to the need for more postoperative analgesics. Intraoperative N-methyl-D-aspartate receptor antagonists, such as ketamine, decrease postoperative opioid use. We therefore tested the hypothesis that intraoperative small-dose ketamine improves postoperative analgesia after major abdominal surgery with remifentanil-based anesthesia. Fifty patients undergoing abdominal surgery under remifentanil-based anesthesia were randomly assigned to intraoperative ketamine or saline (control) supplementation. The initial ketamine dose of 0.15 mg/kg was followed by 2 microg. kg(-1). min(-1). In both groups, desflurane was kept constant at 0.5 minimum alveolar anesthetic concentration without N(2)O, and a remifentanil infusion was titrated to autonomic responses. All patients were given 0.15 mg/kg of morphine 30 min before the end of surgery. Pain scores and morphine consumption were recorded for 24 postoperative h. Less of the remifentanil was required in the Ketamine than in the Control group (P < 0.01). Pain scores were significantly larger in the Control group during the first 15 postoperative min but were subsequently similar in the two groups. The Ketamine patients required postoperative morphine later (P < 0.01) and received less morphine during the first 24 postoperative h: 46 mg (interquartile range, 34-58 mg) versus 69 mg (interquartile range, 41-87 mg, P < 0.01). No psychotomimetic symptoms were noted in either group. In conclusion, supplementing remifentanil-based anesthesia with small-dose ketamine decreases intraoperative remifentanil use and postoperative morphine consumption without increasing the incidence of side effects. Thus, intraoperative small-dose ketamine may be a useful adjuvant to intraoperative remifentanil. IMPLICATIONS: Supplementing remifentanil-based anesthesia with small-dose ketamine decreased intraoperative remifentanil use and postoperative morphine consumption. These data demonstrate that N-methyl-D-aspartate antagonists, such as ketamine, can be a useful adjuvant to intraoperative remifentanil.     

Adding ketamine to morphine for patient-controlled analgesia after major abdominal surgery: a double-blinded, randomized controlled trial.

In this double-blinded, randomized controlled trial we tested if the addition of ketamine to morphine for patient-controlled analgesia (PCA) resulted in improved analgesic efficacy and lower pain scores compared with morphine PCA alone after major abdominal surgery. Seventy-one patients were randomly allocated to receive either morphine 1 mg/mL (Group M) or morphine 1 mg/mL plus ketamine 1 mg/mL (Group MK) delivered via PCA after surgery. No other analgesics or regional blocks were permitted during the 48-h study period. Postoperatively there were no differences between the groups for subjective assessment of analgesic efficacy, pain scores at rest, and on movement, opioid consumption, or adverse events. Group MK patients performed worse in cognitive testing (P = 0.037). There was an increased risk of vivid dreaming in patients who received ketamine (relative risk = 1.8, 95% confidence interval 0.78-4.3). We conclude that small-dose ketamine combined with PCA morphine provides no benefit to patients undergoing major abdominal surgery. Implications: We performed a randomized, controlled trial comparing the use of ketamine and morphine with morphine alone to relieve pain after major abdominal surgery.Ketamine did not improve pain relief and merely increased side effects.