Epidural administration of low-dose morphine combined with clonidine for postoperative analgesia after lumbar disc surgery.

This study evaluates the efficacy and side effects of a low dose of epidural morphine combined with clonidine for postoperative pain relief after lumbar disc surgery. In 36 of 51 patients who accepted the procedure, an epidural catheter was inserted (L1-L2 level). General anesthesia was induced with propofol and sufentanil, and maintained with sevoflurane in O2/N2O. After emergence from anesthesia, epidural analgesia was initiated according to two randomly assigned protocols: 1 mg of morphine with 75 microg of clonidine (Group M) or 12.5 mg of bupivacaine with 75 microg of clonidine (Group B), in 10 mL saline. Piritramide was administered during the first postoperative 24 hours using a patient-controlled analgesia device (PCA). The following parameters were recorded: piritramide consumption during the first 24 hours; pain at rest during the first postoperative hours (D0), during the first night (D1), and during the first mobilization; [visual analogue scale (VAS)]; and the occurrence of drowsiness, motor blockade, respiratory depression, nausea, vomiting, itching, micturition problems, and bladder catheterization during D0 and D1. Epidural administration of morphine-clonidine significantly improved postoperative pain relief and reduced piritramide consumption as compared to epidural bupivacaine-clonidine. Side effects did not differ between groups except for a higher incidence of micturition problems in Group M during D1. The occurrence of bladder catheterization was not significantly higher in that group. We conclude that a low dose of epidural morphine combined with clonidine offers a better postoperative analgesia than does bupivacaine-clonidine. The excellent analgesic conditions were obtained at the expense of a higher incidence of difficulties in initiating micturition.     

Combination of oral clonidine and intravenous low-dose ketamine reduces the consumption of postoperative patient-controlled analgesia morphine after spine surgery

ObjectiveBecause ketamine, clonidine, and morphine modulate nociceptive pain, coadministration of these drugs would augment the activity of postoperative analgesic drugs. The purpose of this study was to evaluate the effects of coadministration of ketamine and clonidine on postoperative morphine consumption in patients after spine surgery.MethodsThe patients undergoing spine surgery were allocated randomly to one of the four study groups, which are as follows: group M (n = 12), intravenously (IV) administered patient-controlled analgesia (PCA) morphine alone; group MK (n = 12), IV-PCA morphine plus intra- and postoperative ketamine; group MC (n = 13), IV-PCA morphine plus oral clonidine premedication; group MCK (n = 12), IV-PCA morphine plus intra- and postoperative ketamine and clonidine premedication. The patients in the MC and MCK groups received 4 μg/kg clonidine orally, whereas those in the MK and MCK groups received IV bolus of ketamine (10 mg) at a rate of 2 mg/kg/hour during anesthesia. Patients were arranged to use IV-PCA mode for administration of drugs, which was programmed to deliver a bolus dose of 2-mg morphine (groups M and MC), or boluses of 2-mg morphine and 2-mg ketamine (groups MK and MCK). Scores of visual analog scale (VAS) for pain, morphine requirement, vital signs, nausea, sedation, and other side effects were followed up to 60 hours after surgery.ResultsAlthough there were significant differences in VAS pain scores at rest 24–48 hours after the surgery, the VAS pain score at movement was similar among the groups. The number of PCA request and cumulative morphine requirement were significantly lower in the MCK group than in the M group.ConclusionThis study results show that the administration of perioperative low-dose ketamine combined with clonidine premedication could reduce the consumption of postoperative PCA morphine following spine surgery.     

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.     

The role of ketamine in preventing fentanyl-induced hyperalgesia and subsequent acute morphine tolerance

Perioperative opioids increase postoperative pain and morphine requirement, suggesting acute opioid tolerance. Furthermore, opioids elicit N-methyl-D-aspartate (NMDA)-dependent pain hypersensitivity. We investigated postfentanyl morphine analgesic effects and the consequences of NMDA-receptor antagonist (ketamine) pretreatment. The rat nociceptive threshold was measured by the paw-pressure vocalization test. Four fentanyl boluses (every 15 min) elicited a dose-dependent (a) increase followed by an immediate decrease of the nociceptive threshold and (b) reduction of the analgesic effect of a subsequent morphine administration (5 mg/kg): -15.8%, -46.6%, -85.1% (4 x 20, 4 x 60, 4 x 100 microg/kg of fentanyl, respectively). Ketamine pretreatment (10 mg/kg) increased the fentanyl analgesic effect (4 x 60 microg/kg), suppressed the immediate hyperalgesic phase, and restored the full effect of a subsequent morphine injection. Fentanyl also elicited a delayed dose-dependent long-lasting decrease of the nociceptive threshold (days) that was prevented by a single ketamine pretreatment before fentanyl. However, a morphine administration at the end of the fentanyl effects restored the long-lasting hyperalgesia. Repeated ketamine administrations were required to obtain a complete preventive effect. Although ketamine had no analgesic effect per se at the dose used herein, our results indicate that sustained NMDA-receptor blocking could be a fruitful therapy for improving postoperative morphine effectiveness. IMPLICATIONS: Fentanyl-induced analgesia is followed by early hyperalgesia (hours), acute tolerance to the analgesic effects of morphine, and long-lasting hyperalgesia (days). All these phenomena are totally prevented by repeated administrations of the NMDA-receptor antagonist, ketamine, simultaneously with fentanyl and morphine administration.     

Lack of a pre-emptive effect of low-dose ketamine on postoperative pain following oral surgery

PURPOSE: The aim of this study was to assess the effect of pre- vs postincisional low-dose iv ketamine on postoperative pain in outpatients scheduled for oral surgery under general anesthesia. METHODS: Eighty-four patients were randomly assigned to receive intravenously saline before and after surgery in Group 1, ketamine 300 microg x kg(-1) iv before and saline after surgery in Group 2, saline before and ketamine 300 microg x kg(-1) iv after surgery in Group 3. Postoperative analgesia consisted of iv proparacetamol and ketoprofen. Rescue analgesia consisted of nalbuphine 200 microg x kg(-1) iv. Analgesia at home consisted of oral ketoprofen, and acetaminophen with codeine as rescue analgesia. A telephone interview was conducted on the first and second postoperative days. RESULTS: There were no significant differences between groups with respect to pain scores, the number of patients requiring nalbuphine in the postanesthesia care unit (PACU), (36.7%, 38.7%, and 39.5% for Groups 1, 2, and 3 respectively), or nalbuphine consumption in the PACU (66.5 microg x kg(-1) +/- 16.8, 75.9 microg x kg(-1) +/- 17.5, 66.7 microg x kg(-1) +/- 21.6 for Groups 1, 2, and 3 respectively). The number of rescue analgesic tablets taken at home, and time to first request for rescue analgesia, sedation scores, or side-effects were similar amongst groups. No patient required nalbuphine in the ambulatory care unit. CONCLUSIONS: There was no benefit to pre-emptive administration of ketamine 300 microg x kg(-1) iv whether administered pre- or postoperatively.     

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.     

Oral clonidine premedication enhances postoperative analgesia by epidural morphine

This study was designed to evaluate the effects of oral clonidine premedication on postoperative analgesia by epidural morphine in a prospective, randomized, double-blinded design. Sixty consenting patients, scheduled for total abdominal hysterectomy, were randomly assigned to one of three groups (n = 20 each); the clonidine-morphine group received oral clonidine 5 microg/kg 90 min before arriving in the operating room and epidural morphine 2 mg before induction of general anesthesia, the clonidine-placebo group received oral clonidine 5 microg/kg and no epidural morphine, and the placebo-morphine group received no clonidine and epidural morphine 2 mg. An epidural catheter was placed at the L1-2 or L2-3 interspace, and 1.5% lidocaine was used for surgical anesthesia in all patients. General anesthesia was then induced with propofol, and maintained with a continuous infusion of propofol and 67% nitrous oxide in oxygen during surgery. Four patients were subsequently withdrawn from the study. After surgery, patient-controlled analgesia using IV morphine was used to assess analgesic requirement. Morphine consumptions determined every 6 h after surgery in the clonidine-morphine and placebo-morphine groups were significantly less than the clonidine-placebo group until 12 h after surgery, whereas those of the clonidine-morphine group were significantly less than the placebo-morphine group from 13 to 42 h after surgery. Visual analog (pain) scale (VAS) scores in the clonidine-morphine group were significantly lower than the placebo-morphine group at 48 h at rest, and at 1, 24, 36, and 48 h with movement. Similarly, VAS scores in the clonidine-morphine group were significantly lower than the clonidine-placebo group at 1 and 6 h both at rest and with movement, whereas VAS scores in the clonidine-placebo group were significantly lower than the placebo-morphine group at 24, 36, and 48 h at rest and with movement. The incidence of nausea and pruritus was similar between groups. We conclude that the combination of oral clonidine and epidural morphine produces more potent and longer lasting postoperative analgesia than either drug alone without increasing the incidence of adverse effects after major gynecologic surgeries. IMPLICATIONS: A small dose of epidural morphine is often used for postoperative analgesia. We found that oral clonidine premedication 5 microg/kg improves the analgesic efficacy of epidural morphine without increasing the incidence of adverse side effects.     

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.     

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.     

Premedication with low dose oral clonidine does not enhance postoperative analgesia of intrathecal morphine

PURPOSE: A number of studies have demonstrated that perioperative intravenous, intrathecal, and epidural clonidine enhance postoperative analgesia. The results of previous studies on the usefulness of oral clonidine on enhancing postoperative analgesia have been mixed. The effect of a single preoperative dose of oral clonidine on postoperative analgesia was assessed in this study. METHODS: Forty-three male patients undergoing radical prostectomy were randomized to receive either 3 microg x kg(-1) clonidine or placebo po 90 min prior to surgery. All patients received isobaric 15 mg bupivacaine and intrathecal 5 microg x kg morphine, followed by a standardized general anesthetic, consisting of thiopental, sufentanil, rocuronium, isoflurane, oxygen and air. Postoperatively, PCA morphine use and visual analogue pain scores were recorded for the first 48 hr. The incidence and severity of side effects such as sedation, nausea, and pruritus were assessed, as well as patient satisfaction. Usage of PCA morphine was compared. RESULTS: There was no difference in total morphine requirements between the placebo and oral clonidine groups, nor in six hourly morphine usage (P = 0.96). Second, there was no difference in visual analogue pain scores, or the incidence of side effects. Patient satisfaction was high in both groups and again, no differences between groups was noted. CONCLUSIONS: Oral clonidine 3 microg x kg(-1) as a premedication does not prolong the effect of intrathecal morphine: there was no difference in PCA morphine requirements (P = 0.96). Clonidine did not effect the incidence or severity of nausea or pruritus.     

Epidural clonidine enhances postoperative analgesia from a combined low-dose epidural bupivacaine and morphine regimen.

In a randomized, double-blind, placebo-controlled trial, the value of adding clonidine to a low-dose epidural regimen for postoperative pain treatment was assessed. Twenty-four patients scheduled for hysterectomy during combined thoracic epidural (bupivacaine and morphine) and general anesthesia were studied. Postoperative analgesia consisted of epidural bupivacaine (5 mg/h) and morphine (0.1 mg/h) for 12 h. In addition, the patients randomly received clonidine (75 micrograms), followed by an infusion of 18.75 micrograms/h or saline solution (placebo) epidurally. Pain was evaluated at rest, during cough, and during mobilization every hour. Sensory level of analgesia was evaluated by pinprick. We found no significant difference in pain scores at rest between the clonidine and placebo groups but an enhanced analgesic effect by clonidine during cough and mobilization (P less than 0.05). Arterial blood pressure decreased significantly during clonidine infusion and remained lower than in the control group throughout the study. We conclude that a continuous low-dose epidural clonidine infusion enhances analgesia from a combined low-dose epidural bupivacaine and morphine regimen after hysterectomy; however, the concomitant decrease in arterial blood pressure during epidural clonidine deserves further study before such a regimen can be recommended.     

Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular clonidine and/or morphine

Both clonidine, an alpha(2) agonist, and morphine, an opioid agonist, provide enhanced patient analgesia after arthroscopic knee surgery when administered via the intraarticular (IA) route. Clonidine potentiates morphine analgesia in the animal model. We designed this study to determine whether clonidine or morphine results in better analgesia and whether their combination would provide superior analgesia to either drug alone. We evaluated 60 patients undergoing arthroscopic knee meniscus repair under local anesthesia with sedation. After surgery, patients were randomized into four IA groups: Group B received 30 mL 0.25% bupivacaine; Group BC received 30 mL 0.25% bupivacaine and clonidine 1 microg/kg; Group BM received 30 mL 0.25% bupivacaine and morphine 3 mg; and Group BCM received 30 mL 0.25% bupivacaine, clonidine 1 microg/kg, and morphine 3 mg. This study revealed a significant benefit from the individual IA administration of both clonidine and morphine. The combination of these drugs resulted in decreased postoperative pain and analgesic use, as well as an increased analgesic duration compared with either drug alone. We conclude that IA clonidine and morphine improved comfort compared with either drug alone in patients undergoing knee arthroscopy.     

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.     

Intrathecal clonidine added to a bupivacaine-morphine spinal anesthetic improves postoperative analgesia for total knee arthroplasty

Postoperative pain after total knee arthroplasty (TKA) is severe and can complicate early physical therapy. We tested the hypothesis that intrathecal clonidine would improve postoperative analgesia for TKA using a hyperbaric bupivacaine spinal anesthetic. In a double-blinded, placebo-controlled protocol, 81 ASA physical status I-III patients undergoing either a single or bilateral TKA were randomized into 4 groups with the following 2-mL solutions added to 15 mg of hyperbaric bupivacaine: 1) sterile saline, 2) morphine (250 microg), 3) morphine (250 microg) with clonidine (25 microg), and 4) morphine (250 microg) with clonidine (75 microg). At 1, 2, 4, 6, 12, and 24 h postoperatively, we measured visual analog scales (VAS), cumulative IV morphine consumption, hemodynamics, nausea, ancillary drugs, and side effects. Our primary comparison was between the clonidine with morphine groups versus the morphine group. We found that the combined administration of intrathecal clonidine and morphine decreased 24 h IV morphine consumption by 13 mg (P = 0.028) when compared with intrathecal morphine alone. This corresponded to a decrease in the VAS score of 1.3 cm at 24 h postoperatively (P = 0.047). Adverse side effects were similar among all groups with the exception of more relative hypotension in the clonidine groups through postoperative hour 6. We conclude that the coadministration of intrathecal clonidine and morphine decreases the 24-h IV morphine consumption and improves the 24-h VAS score when compared with intrathecal morphine alone. IMPLICATIONS: In this prospective, randomized, double-blinded, and placebo-controlled trial, we identify an effective postoperative analgesic approach in total knee replacement surgery. Intrathecal morphine (250 microg) combined with clonidine (25 or 75 microg) provided superior analgesia compared with intrathecal morphine alone.     

Low-dose intravenous ketamine and clonidine for poor postoperative opioid responsiveness: a double blind randomized study

In the immediate postoperative period, some patients present with pain that responds poorly to intravenous opioids. In a double-blind randomized study, we tested the hypothesis that administering small doses of intravenous ketamine (0.125 mg/kg) combined with clonidine (0.5 microg/kg) would enhance the speed of onset and the quality of an opioid analgesic regimen in patients who initially responded poorly to opioids. We enrolled 68 patients in the study, all physical status I to III according to the American Society of Anesthesiologists classification. If the patient's numerical rating scale (NRS) score remained > or = 5 after an initial intravenous injection of 10 mg piritramide (2-mg boluses every 5 minutes) in the post-anesthesia care unit, patients were randomized to either intravenous placebo (sodium chloride 0.9%) or active substances (ketamine 0.125 mg/kg plus clonidine 0.5 microg/kg). Fifteen minutes after administration of either placebo or active agents, patients with severe pain (NRS > 4) again received intravenous opioids until NRS < 4. The primary endpoint of the study was to reduce by 20 minutes the time necessary to achieve an NRS < 4. There was no statistically significant difference between the two groups regarding the time required for patients to achieve an NRS < 4. It was concluded that in the immediate postoperative period, the acute administration of small combined doses of intravenous ketamine (0.125 mg/kg) and clonidine (0.5 mirog/kg) does not reduce the onset of an opioid-based analgesia in patients with an initial poor response to intravenous opioids.     

Does ketamine have preemptive effects in women undergoing abdominal hysterectomy procedures?

Ketamine may produce "preemptive" analgesia when administered before surgically induced trauma. Therefore, we hypothesized that pre- versus postincisional administration of ketamine would improve pain control after abdominal hysterectomy procedures. Eighty-nine patients were randomly assigned to one of three treatment groups according to a placebo-controlled, double-blinded protocol: Group 1 (placebo) received saline 0.04 mL/kg IV immediately before and after surgery; Group 2 (preincision), received ketamine 0.4 mg/kg IV before skin incision and saline at the end of the operation; and Group 3 (postincision), received saline before skin incision, and ketamine 0.4 mg/kg IV was given after skin closure. The general anesthetic technique was standardized in all three treatment groups. During the first postoperative hour, Group 3 experienced significantly less pain than Groups 1 and 2, as assessed by using both visual analog and verbal rating scales. There were no significant differences between Groups 1 and 2 with respect to pain scores, postoperative opioid analgesic requirements, and incidence of postoperative nausea and vomiting. We conclude that a single dose of ketamine 0.4 mg/kg IV fails to produce preemptive analgesic effects. Implications: Even though ketamine 0.4 mg/kg IV has short-lasting acute analgesic effects, it failed to produce a preemptive effect when given before abdominal hysterectomy procedures.     

The short-lasting analgesia and long-term antihyperalgesic effect of intrathecal clonidine in patients undergoing colonic surgery

In this study, we investigated the antihyperalgesic effect of clonidine after surgery. Sixty patients undergoing right colic resection were studied. Patients were randomized to receive prior to general anesthesia a 2-mL intrathecal (IT) injection of 300 microg of clonidine or saline, or 10 mg of bupivacaine. General anesthesia was achieved using a target concentration propofol infusion and monitored using bispectral index. Postoperative analgesia was provided by morphine IV given through a patient-controlled analgesia device. Postoperative analgesia was assessed by morphine requirements and visual analog scale pain scores at rest, cough, and movement during the first 72 h. Mechanical hyperalgesia was measured by von Frey filaments. Patients were questioned regarding residual pain at 2 wk,1, 6, and 12 mo. The patient-controlled analgesia morphine requirements were significantly smaller in the IT clonidine group (31.5 +/- 12 versus 91 +/- 25.5 and 43 +/- 15 mg, respectively, in groups clonidine, saline, and bupivacaine: P < 0.05 at 72 postoperative hours). The area of hyperalgesia at 72 h was 3 +/- 5 cm(2) in the clonidine group versus 90 +/- 30 and 35 +/- 20 cm(2) in the saline and bupivacaine groups (P < 0.05). At 6 mo, fewer patients in the clonidine group experienced residual pain than in the saline group (0 of 20 versus 6 of 20, P < 0.05). We conclude that both intraoperative spinal clonidine and bupivacaine improve immediate postoperative analgesia. IT clonidine was, however, more potent than IT bupivacaine to reduce postoperative secondary hyperalgesia. IMPLICATIONS: Spinal clonidine contributes to the reduction of secondary hyperalgesia in patients recovering from abdominal surgery.     

Analgesia for paediatric tonsillectomy and adenoidectomy with intramuscular clonidine

BACKGROUND: After undergoing tonsillectomy and adenoidectomy (T&A), children may experience significant pain. Clonidine, an alpha2 agonist, exhibits significant analgesic properties. The current investigation sought to determine whether intramuscular (I.M.) clonidine would decrease pain in paediatric patients undergoing T&A. METHODS: Thirty-nine children undergoing elective T&A were studied. Following inhalational anaesthetic induction, fentanyl (2 microg x kg(-1)) was given intravenously, acetaminophen (paracetamol) (30 mg.kg-1) was given rectally and the children then randomly received an i.m. injection of either normal saline or clonidine (2 microg x kg(-1)). Perioperative analgesic requirements in the postanaesthesia care unit and at home following hospital discharge were evaluated. RESULTS: There were no significant demographic, analgesic consumption, haemodynamic or pain score differences between the groups. CONCLUSIONS: We do not recommend adding i.m. clonidine (2 microg x kg(-1)) to the analgesic regimen of children undergoing tonsillectomy and adenoidectomy.     

The persisting analgesic effect of low-dose intravenous ketamine after spinal anaesthesia for caesarean section

BACKGROUND AND OBJECTIVES: To compare the analgesic effects of intrathecal fentanyl and low-dose intravenous ketamine as adjuvants to intrathecal bupivacaine for Caesarean section. METHODS: Ninety elective Caesarean section patients were randomized into three groups. Spinal anaesthesia was performed with 15 mg hyperbaric bupivacaine in all groups. Ketamine (0.15 mg kg(-1)) or an equal volume of normal saline was given intravenously immediately after initiating spinal anaesthesia in the ketamine and control group, respectively. In the fentanyl group, 10 microg fentanyl was added to the intrathecal bupivacaine. Arterial pressures, heart rate values, adverse effects, the time of first request for postoperative analgesia, visual analogue pain scores, total analgesic consumptions at 24 and 48 h were recorded in all patients. RESULTS: The time to first request for analgesia was significantly longer in the ketamine (197 min) and fentanyl (165 min) groups compared to the control group (144 min). Postoperative pain scores were significantly lower in the ketamine group than in both other groups. Although the analgesic requirements during first 24 h were significantly lower in the ketamine group, there was no significant difference between the groups during the following 24 h. CONCLUSION: Intravenous low-dose ketamine combined with intrathecal bupivacaine for Caesarean section provides longer postoperative analgesia and lower postoperative analgesic consumption than bupivacaine alone suggesting a pre-emptive effect.     

Synergistic antinociceptive effects of ketamine and morphine in the orofacial capsaicin test in the rat

BACKGROUND: The clinical efficacy of the noncompetitive N-methyl-d-aspartate receptor antagonist ketamine for treating orofacial pain has already been reported. Side effects related to psychotomimetic disturbances, however, limit ketamine use as an analgesic. Theoretically, this limitation could be minimized by using low doses of ketamine in combination with other analgesics. In the present study, the potential synergistic antinociceptive interaction between ketamine and morphine in the orofacial capsaicin test in rats was investigated. METHODS: Male Sprague-Dawley rats were subcutaneously injected with solvent, ketamine, morphine, or combination of both drugs. Thirty minutes later, the orofacial capsaicin test was performed by injecting of 1.5 microg/25 microl of a capsaicin solution into the vibrissa pad. Animal behavior was recorded on videotape and analyzed off-line. The total time spent on rubbing-scratching nociceptive behavior during a period of 42 min was measured. RESULTS: Subcutaneously administered ketamine (0.4, 1.25, 4, 12.5 mg/kg), morphine (0.5, 1, 2, 4 mg/kg) and ketamine + morphine (0.20 + 0.12, 0.40 + 0.24, 0.80 + 0.49, 1.61 + 0.97, 3.21 + 1.94 mg/kg) reduced the rat facial rubbing-scratching behavior in a dose-dependent manner. Isobolographic analysis showed that the ketamine + morphine association inhibited the studied behavior in a superadditive manner. CONCLUSIONS: These results indicate that ketamine and morphine have antinociceptive effects on the orofacial capsaicin test. Furthermore, their combination produces synergistic antinociception. It is therefore suggested that, used together, ketamine and morphine might be clinically efficient at lower doses than those currently used when administered separately. This could provide a useful strategy for the clinical management of orofacial pain.