A single small dose of postoperative ketamine provides rapid and sustained improvement in morphine analgesia in the presence of morphine-resistant pain

It is a common clinical observation that postoperative pain may be resistant to morphine. The analgesic potentials of ketamine have also been well documented. In this study, we evaluated the effects of postoperative coadministration of small doses of ketamine and morphine on pain intensity, SpO(2), and subjectively rated variables in surgical patients who underwent standardized general anesthesia and complained of pain (> or =6 of 10 on a visual analog scale [VAS]) despite >0.1 mg/kg of i.v. morphine administration within 30 min. Patients randomly received up to three boluses of 30 microg/kg of morphine plus saline (MS; n = 114) or 15 microg/kg of morphine plus 250 microg/kg of ketamine (MK; n = 131) within 10 min in a double-blinded manner. The MS group's pain VAS scores were 5.5 +/- 1.18 and 3.8 +/- 0.9 after 10 and 120 min, respectively, after 2.52 +/- 0.56 injections, versus the MK group's VAS scores of 2.94 +/- 1.28 and 1.47 +/- 0.65, respectively (P < 0.001), after 1.35 +/- 0.56 injections (P < 0.001). The 10-min level of wakefulness (1-10 VAS) in the MS group was significantly (P < 0.001) less (6.1 +/- 1.5) than the MK group's (8.37 +/- 1.19). SpO(2) decreased by 0.26% in the MS group but increased by 1.71% in the MK patients at the 10-min time point (P < 0.001). Thirty MS versus nine MK patients (P < 0.001) experienced nausea/vomiting; nine MK patients sustained a 2-min light-headed sensation, and one patient had a weird dream after the second drug injection. IMPLICATIONS: A small-dose ketamine and morphine regimen interrupted severe postoperative pain that was not relieved previously by morphine. Ketamine reduced morphine consumption and provided rapid and sustained improvement in morphine analgesia and in subjective feelings of well-being, without unacceptable side effects.     

Intraoperative intravenous ketamine in combination with epidural analgesia: postoperative analgesia after renal surgery

We designed this double-blinded, randomized, controlled study to evaluate the effect of small-dose ketamine IV in combination with epidural morphine and bupivacaine on postoperative pain after renal surgery. An epidural catheter was inserted, and the administration of morphine and bupivacaine was started before surgery. Forty patients were assigned to one of two groups (ketamine or control). The ketamine group was administered a ketamine bolus and infusion during surgery. The median visual analog pain scale (VAS) scores at rest were significantly lower in the ketamine group during the first 6 h (P < 0.01). VAS pain scores on coughing were also significantly lower in the ketamine group (P < 0.01). Cumulative postoperative total analgesic consumption was less in the ketamine group on Days 1 and 2 (P < 0.001). The first analgesic demand time was shorter in the control group (9.2 +/- 11.5 min) than in the ketamine group (22.3 +/- 17.1 min) (P < 0.0001). The incidence of nausea and pruritus was more frequent in the control group (P < 0.05). In conclusion, postoperative analgesia was more effective when spinal cord and brain sensitization were blocked by a combination of epidural morphine/bupivacaine and IV ketamine. IMPLICATIONS: Renal nociception conducted multisegmentally by both the spinal nerves (T10 to L1) and the vagus nerve cannot be blocked by epidural analgesia alone. We demonstrated that IV ketamine had an improved analgesic or opioid-sparing effect when it was combined with epidural bupivacaine and morphine after renal 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.     

Preoperative ketamine improves postoperative analgesia after gynecologic laparoscopic surgery

In this study, we evaluated the preemptive effect of a small dose of ketamine on postoperative wound pain. In a randomized, double-blinded, controlled trial, we compared the analgesic requirement in patients receiving preincision ketamine with ketamine after skin closure or placebo after gynecologic laparoscopic surgery. One-hundred-thirty-five patients were randomly assigned to receive preincision or postoperative ketamine 0.15 mg/kg or saline IV. Anesthetic technique was standardized. Patients were interviewed regularly up to 4 wk after surgery. Pain score, morphine consumption, side effects, and quality of recovery score were recorded. Patients receiving preincision ketamine had a lower pain score in the first 6 h after operation compared with the postoperative (P = 0.001) or placebo groups (P < 0.001). The mean (95% confidence intervals) time to first request for analgesia in the preincision group, 1.8 h (1.4-2.1), was longer than the postoperative group, 1.2 h (0.9-1.5; P < 0.001), or the placebo group, 0.7 h (0.4-0.9; P < 0.001). The mean +/- SD morphine consumption in the preincision group, 1.5 +/- 2.0 mg, was less than that in the postoperative group, 2.9 +/- 3.1 mg (P = 0.04) and the placebo group, 3.4 +/- 2.7 mg (P = 0.003). There was no significant difference among groups with respect to hemodynamic variables or side effects. No patient complained of hallucinations or nightmares. We conclude that a small dose of ketamine is not only safe, but it also provides preemptive analgesia in patients undergoing gynecologic laparoscopic surgery. IMPLICATIONS: In women undergoing laparoscopic gynecologic surgery, a small preoperative dose of ketamine (0.15 mg/kg) produced preemptive analgesia. There were no significant hemodynamic and psychological side effects with this dose.     

Ketamine reduces swallowing-evoked pain after paediatric tonsillectomy

BACKGROUND: Ketamine efficacy as an analgesic adjuvant has been studied in several clinical settings with conflicting results. The aim of this study was to investigate the effect of ketamine on spontaneous and swallowing-evoked pain after tonsillectomy. METHODS: Fifty children were randomized to receive premedication with either ketamine 0.1 mg kg(-1) i.m. or placebo given 20 min before induction of a standard general anaesthesia. All children received rectal diclofenac 2 mg kg(-1) and fentanyl 1 micro g kg(-1) i.v. before surgery. RESULTS: The ketamine group showed significantly lower pain scores both at rest and on swallowing, with less total paracetamol consumption (P < 0.05) during the 24 h after surgery. Significantly more patients required postoperative morphine titration in the control group (P < 0.05). The time to the first oral intake, and duration of i.v. hydration, were significantly shorter and the quality of oral intake was significantly better in the ketamine group (P < 0.05). There were no differences in the incidence of vomiting or dreaming between the groups. CONCLUSION: Premedication with a small dose of ketamine reduces swallowing-evoked pain after tonsillectomy in children who received an analgesic regimen combining an opioid and a NSAID.     

The analgesic effect of nitroglycerin added to lidocaine on intravenous regional anesthesia

We evaluated the analgesic effect of nitroglycerine (NTG) when added to lidocaine in IV regional anesthesia. Thirty patients undergoing hand surgery were randomly assigned to two groups. The control group (group C, n = 15) received a total dose of 40 mL with 3 mg/kg of lidocaine diluted with saline, and the NTG group (group NTG, n = 15) received an additional 200 mug NTG. Hemodynamic variables, tourniquet pain measured before and 1, 5, 10, 20, and 30 min after tourniquet inflation, and analgesic requirements were recorded during the operation. After the tourniquet deflation, at 1 and 30 min and 2 and 4 h, visual analog scale (VAS) score, time to first analgesic requirement, total analgesic consumption in the first 24 h after operation, and side effects were noted. Shortened sensory and motor block onset time (3.2 +/- 1.1 versus 4.5 +/- 1.2 min; P = 0.01 and 3.3 +/- 1.6 versus 5.2 +/- 1.8; P = 0.009 in group NTG and group C, respectively), prolonged sensory and motor block recovery times (6.8 +/- 1.6 versus 3.1 +/- 1.2 min P < 0.0001 and 7.3 +/- 1.3 versus 3.6 +/- 0.8 P < 0.0001 in group NTG and group C, respectively), shortened VAS scores of tourniquet pain (P = 0.023), and improved quality of anesthesia were found in group NTG (P < 0.05). VAS scores were lower in group NTG after tourniquet release and in the postoperative period (P = 0.001). First analgesic requirement time was longer in group NTG (225 +/- 74 min versus 39 +/- 33 min) than in group C (P < 0.0001). Postoperative analgesic requirements were significantly smaller in group NTG (P < 0.0001) but the side effects were similar in both groups. We conclude that the addition of NTG to lidocaine for IV regional anesthesia improves sensory and motor block, tourniquet pain, and postoperative analgesia without side effects.     

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.     

Low dose intrathecal morphine and postoperative pain relief in elderly patients]

Patient (ASA PS I-III, mean age 68 +/- 14 yr) who had undergone lower extremity surgery under spinal anesthesia were studied to determine the effect of intrathecal administration of morphine 0.1 mg on intra- and postoperative pain relief and its side effects. They were randomly divided into control (C) and intrathecal morphine (M) groups (n = 25, respectively) and received 10 mg tetracaine in 4 ml of a quarter saline with 7.5 micrograms epinephrine. Incidence of intraoperative tourniquet pain was significantly lower in M group (36.8%) than in C group (64.3%). Postoperative pain was examined in terms of the duration until the first supplemental analgesic within 24 hr. The mean duration was 7.0 +/- 4.3 hr in the control group, but 11 patients in the M group needed it within 24 hr (18.1 +/- 6.8 hr, excluding 6 patients who did not receive analgesic). Although incidences of postoperative nausea, vomiting, and itching were higher in M group than in C group, none required antiemetic or naloxone. Both groups showed no difference in postoperative respiratory depression measured by apnea monitor (Eden Trace II, Mallinkrodt Japan, Tokyo). The results suggest that a low dose of intrathecal morphine is effective on postoperative 24 hr pain relief in elderly patients and that its side effects are negligible.     

A randomised, controlled study of peri-operative low dose s(+)-ketamine in combination with postoperative patient-controlled s(+)-ketamine and morphine after radical prostatectomy

In a randomised, double-blind prospective study we compared the effects on postoperative pain and analgesic consumption of intra-operative s(+)-ketamine (100 microg.kg-1 bolus and a continuous infusion of 2 microg.kg-1.min-1) followed by postoperative patient-controlled analgesia with morphine (1 mg per bolus) plus s(+)-ketamine (0.5 mg per bolus), or intra-operative saline followed by postoperative patient-controlled analgesia morphine (1 mg per bolus) alone. A total of 28 male patients undergoing radical prostatectomy were studied. Morphine consumption, pain scores, pressure algometry and adverse effects were recorded for 48 h after surgery. Cumulative morphine consumption was significantly lower in the ketamine/morphine group (47.9 +/- 26.2 mg) than in the saline/morphine group (73.4 +/- 34.8 mg; p = 0.049). Pain scores at rest were significantly lower in the ketamine/morphine group across the 48-h study period (p = 0.01). No significant differences were found in pressure algometry measurements or the occurrence of adverse effects.     

Perioperative nimodipine and postoperative analgesia

There is experimental evidence that nimodipine, an L-type dihydropiridine calcium channel blocker with relatively high blood-brain barrier penetration, enhances the antinociceptive properties of morphine. We tested the hypothesis that oral nimodipine taken preoperatively and 6 hourly for 48 h postoperatively would reduce visual analog scale pain scores and morphine consumption in morphine-naive patients with acute postoperative pain. Forty patients undergoing total knee replacement surgery (age 70 +/- 7 yr, 28 male) were randomized by computer-generated numbers to receive capsules containing either nimodipine 30 mg or placebo in a double-blind study design. All patients received 3 capsules (nimodipine 90 mg or placebo) 1-2 h before induction of anesthesia followed by oral nimodipine 30 mg or placebo 6 hourly for 48 hours postoperatively. Spinal anesthesia was induced with hyperbaric bupivacaine 0.5% (2.4-3.0 mL) and fluids and ephedrine were given at the discretion of the anesthesiologist. Morphine patient-controlled analgesia (PCA, bolus 1 mg, lockout 5 min) was given for postoperative analgesia. Primary outcome measures were visual analog pain scores at rest and on moving (sitting forward) and PCA morphine consumption. Morphine consumption was significantly larger in nimodipine patients at 12 h (39 +/- 18 versus 29 +/- 15; P = 0.04), 24 h (62 +/- 23 versus 45 +/- 24; P = 0.02), and 48 h (88 +/- 34 versus 61 +/- 27; P = 0.01). There were no significant differences in pain scores at rest or moving or in time to first use of morphine analgesia. This study has demonstrated increased morphine consumption after 12 h in postoperative patients receiving nimodipine, suggesting that, in patients undergoing knee replacement surgery, it has no adjunctive analgesic effect and may actually inhibit the analgesic effect of morphine.     

Low-dose Intravenous Ketamine Potentiates Epidural Analgesia after Thoracotomy

Background: Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain.

Methods: Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg [middle dot] kg-1 [middle dot] h-1 [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery.

Results: The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03).     

A comparative study of the analgesic effect of patient-controlled morphine, pethidine, and tramadol for postoperative pain management after abdominal hysterectomy

We designed this prospective, randomized, double-blind study to compare the analgesic effectiveness and side effects of IV patient-controlled morphine, pethidine, and tramadol for postoperative pain management. One-hundred-twenty-six ASA physical status I or II patients undergoing abdominal hysterectomy were randomly allocated to receive IV-patient controlled morphine (M), pethidine (P), or tramadol (T) for postoperative analgesia. The cumulative analgesic consumption over 24 h was 25.7 +/- 9.5 mg for morphine, 266 +/- 90 mg for pethidine, and 320 +/- 10 mg for tramadol. The average supplementary fentanyl dose used was significantly higher in group T than in groups M and P (P < 0.05). In conclusion, morphine, pethidine, and tramadol resulted in equivalent pain scores and side effects, but tramadol group T required more rescue analgesic doses of fentanyl.     

Anesthesia and immunosuppression in an experimental model

The purpose of the present work was to study: (1) if anesthesia induces changes in the helper/cytotoxic/suppressor T cell ratio in the rat spleen, and (2) if there is any difference between two anesthetic methods usually employed in rat experimentation. 50 Fisher 344 rats were allotted into 5 groups. In group A (control), a splenectomy was performed in an average time of 3 min under ether anesthesia. In groups B1 and B2, the rats anesthetized for 1 h with ether (group B1) or with one single dose of ketamine + atropine + diazepam (group B2) and then underwent splenectomy. Groups C1 and C2 were similar to groups B1 and B2 but splenectomy was performed 24 h later, under ether anesthesia during 3 min. T helper (Th) and T cytotoxic-suppressor (Ts-c) cells were identified in periarterial and follicular spleen tissue by means of an immunohistologic analysis using an immunoperoxidase technique with monoclonal antibodies. In periarterial tissue the Th/Ts-c ratio (mean +/- SE) was: group A, 1.61 +/- 0.11; group B1, 1.10 +/- 0.1; group B2, 1.28 +/- 0.11; group C1, 0.85 +/- 0.08, and group C2, 1.23 +/- 0.12. The differences between groups A and B1, C1 and C2 were statistically significant (t = 2.2833) as well as the difference between groups C1 and C2 (t = 2.5223). The Th/Ts-c ratio was also compared when equal to 1 or less than 1. The difference between groups A and C1 was statistically significant (p less than 0.05) as well. In follicular tissue the ratio was 1 in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Low-dose intravenous ketamine potentiates epidural analgesia after thoracotomy

BACKGROUND: Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain. METHODS: Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg . kg(-1) . h(-1) [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery. RESULTS: The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03). CONCLUSIONS: Very-low-dose ketamine (0.05 mg . kg(-1) . h(-1)) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain.     

Morphine tolerance decreases the analgesic effects of ketamine in mice

Previous studies have shown that ketamine interacts with opiate receptors, and it has been suggested that ketamine-induced analgesia is mediated through opiate receptors. If so, ketamine should produce less analgesia in morphine tolerant animals, just as morphine does. To test this hypothesis, the analgesic effects of ketamine were tested in mice implanted with placebo pellets and in mice made tolerant to morphine through implantation of morphine pellets, using the abdominal constriction test. The test consisted of ip injection of 1% acetic acid, which caused stretching of hind limbs and constriction of abdominal muscles, also called writing. The number of writhes was counted for each mouse 10-15 min following acetic acid injection. Morphine pellet implanted mice treated with saline writhed 12.2 +/- 0.8 times (mean +/- SEM), not significantly different from 9.8 +/- 0.9 times seen in placebo pellet implanted mice. Treatment of the animals with ketamine at three doses of 20, 25, and 30 mg/kg, subcutaneously (sc), reduced the number of writhes in the placebo pellet implanted group to 5.8 +/- 0.8, 4.2 +/- 0.7, and 1.3 +/- 0.3, respectively. In the morphine pellet-implanted group, with the same doses of ketamine, the numbers of writhes were 10 +/- 0.9, 9.3 +/- 1.1, and 5.2 +/- 0.9, respectively. Morphine-tolerant animals writhed significantly more at each dose of ketamine, indicating that they were cross tolerant to the analgesic effects of ketamine.     

Pre-emptive analgesia with ketamine, morphine and epidural lidocaine prior to total knee replacement

Purpose

Pre-emptive analgesia can improve postoperative pain management. The purpose of this study was to examine the effectiveness of ketamine as a pre-emptive analgesic as previous studies have shown the involvement of N-methyl-D-Aspartate (NMDA) receptor in neuroplasticity.

Methods

Forty-five ASA 1–2 patients, undergoing unilateral total knee replacement were studied. In the study groups, epidural lidocaine was used as the primary anaesthestic. Patients received ketamine + morphine epidurally 30 min either before (group EB) or after skin incision (group EA). Group G patients received general anaesthesia and ketamine + morphine were given 30 min after skin incision via an epidural catheter used for postoperative pain control. Epidural morphine and ketamine in lidocaine was given to all patients at the end of surgery and every 12 hr for three days for analgesia supplemented with PCA morphine. The time until first PCA trigger, morphine consumption, pain scores, satisfaction scores, and morphine related side effects were recorded at 6, 12, 24, 48 and 72 hr after surgery.

Results

Epidural ketamine plus morphine with lidocaine before surgical incision produced better pain relief and patient satisfaction than when given after incision. A longer time to PCA and decreased morphine consumption were observed in group EB than in group G. In group EA, epidural anaesthesia also produced some pre-emptive analgesic effect compared with general anaesthesia shown by decreased morphine consumption.

Conclusions

Administration of ketamine plus morphine with epidural lidocaine anaesthesia before surgery provided improved postoperative analgesia compared with general anaesthesia alone or when analgesics were given after skin incision.     

Bupivacaine/ketamine is superior to intra-articu-lar ketamine analgesia following arthroscopic knee surgery

PURPOSE: Centroneuraxial and parenteral administration of ketamine has been shown to produce analgesia. However, this analgesia is limited by adverse effects. The purpose of this study was to determine whether ketamine alone or in combination with bupivacaine provides superior pain relief after surgery in patients undergoing knee arthroscopy. METHODS: Sixty patients (classified as ASA status I or II) under-going arthroscopic meniscus repair during general anesthesia were randomized to receive 1.0 mg x kg(-1) ketamine (Group K), 0.25% bupivacaine (Group B) or a combination of 1.0 mg x kg(-1) ketamine and 0.25% bupivacaine (Group BK) to a total volume of 20 mL by intra-articular route following surgery. Visual analogue score in the postanesthesia care unit at 0.5, 1, 2, 4, 6, 8, 12 and 24 hr after surgery, duration of analgesia and subsequent 24 hr consumption of rescue analgesic (dextroproxyphene/acetaminophen) were evaluated. RESULTS: The results showed significantly higher pain scores in Group K as compared to Group B and Group BK. The duration of analgesia was significantly shorter in Group K as compared to the other two groups (Group B = 5.7 +/- 0.8; Group BK = 5.1 +/- 1.1 vs Group K = 1.7 +/- 0.9 hr; P < 0.05). However, 24 hr consumption of analgesic was similar in the three groups. CONCLUSION: We conclude that intra-articular bupivacaine-ketamine combination provides better pain relief than intra-articular ketamine after day care arthroscopic knee surgery.     

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.     

Intravenous regional anesthesia using lidocaine and magnesium

We conducted this study to evaluate the effects of magnesium, when added to lidocaine for IV regional anesthesia (IVRA), on tourniquet pain. Thirty patients undergoing elective hand surgery during IVRA were randomly assigned to two groups. IVRA was achieved with 10 mL of saline plus 3 mg/kg lidocaine 0.5% diluted with saline to a total of 40 mL in group C or with 10 mL of 15% magnesium sulfate (12.4 mmol) plus 3 mg/kg lidocaine 0.5% diluted with saline to a total of 40 mL in group M. Injection pain, sensory and motor block onset and recovery time, tourniquet pain, and anesthesia quality were noted. Patients were instructed to receive 75 mg of IM diclofenac when the visual analog scale (VAS) score was >4, and analgesic requirements were recorded. Sensory and motor block onset times were shorter and recovery times were prolonged in group M (P < 0.05). VAS scores of tourniquet pain were lower in group M at 15, 20, 30, 40, and 50 min (P < 0.001). Anesthesia quality, as determined by the anesthesiologist and surgeon, was better in group M (P < 0.05). Time to the first postoperative analgesic request in group C was 95 +/- 29 min and in group M was 155 +/- 38 min (P < 0.05). Postoperative VAS scores were higher for the first postoperative 6 h in group C (P < 0.05). Diclofenac consumption was significantly less in group M (50 +/- 35 mg) when compared with group C (130 + 55 mg) (P < 0.05). We conclude that magnesium as an adjunct to lidocaine improves the quality of anesthesia and analgesia in IVRA.