Epidural clonidine or bupivacaine as the sole analgesic agent during and after abdominal surgery: a comparative study.

BACKGROUND: The rationale of this study was to compare high-dose epidural clonidine with a more commonly used agent, such as bupivacaine. This was performed to give a more objective idea of the relative analgesic potency of epidural clonidine. METHODS: Sixty patients undergoing intestinal surgery during propofol anesthesia were studied. At induction, the patients received epidurally a dose of 10 micrograms/kg [corrected] clonidine in 7 ml saline followed by an infusion of 6 micrograms [corrected] x kg(-1) x h(-1) (7 ml/h) (group 1, n = 20), a dose of 7 ml bupivacaine, 0.5%, followed by 7 ml/h bupivacaine, 0.25% (group 2, n = 20), or a dose of 7 ml bupivacaine, 0.25%, followed by 7 ml/h bupivacaine, 0.125% (group 3, n = 20). Intraoperatively, increases in arterial blood pressure or heart rate not responding to propofol (0.5 mg/kg) were treated with intravenous alfentanil (0.05 mg/kg). Additional doses of propofol were given to maintain an adequate bispectral index. The epidural infusions were maintained for 12 h. In cases of subjective visual analogue pain scores up to 5 cm at rest or up to 8 cm during coughing, the patients were given access to a patient-controlled analgesia device. RESULTS: During anesthesia, patients in group 1 required less propofol than those in groups 2 and 3 (78 [36-142] mg vs. 229 [184-252] mg and 362 [295-458] mg; P < 0.05) and less alfentanil than patients in group 3 (0 [0-0] mg vs. 11 [6-20] mg; P < 0.05). Analgesia lasted 380 min (range, 180-645 min) in group 1 versus 30 min (range, 25-40 min) in group 2 and 22 min (range, 12.5-42 min) in group 3 (P < 0.05). There was no suggestion of a hemodynamic difference among the three groups except for heart rates that were significantly reduced in patients in group 1. Sedation scores were significantly higher in this group during the first 2 h postoperatively. CONCLUSION: Our results show that high doses of epidural clonidine potentiate general anesthetics and provide more efficient postoperative analgesia than the two bupivacaine dosage regimens investigated.     

Epidural Clonidine Used as the Sole Analgesic Agent during and after Abdominal Surgery: A Dose-Response Study

Background: Many studies have shown the beneficial effect of epidural clonidine in postoperative pain management. In these studies, the patients received local anesthetics, opioids, or both in combination with clonidine. Due to the interactive potentiation of those drugs, the importance of the intrinsic analgesic properties of the alpha2 -adrenoceptor agonist is difficult to establish. The authors investigated the analgesic potency of epidural clonidine when used as the sole analgesic agent during and after major abdominal surgery.

Methods: Fifty young adult patients undergoing intestinal surgery under general anesthesia with propofol were studied. At induction, the patients received epidurally either an initial dose of 2 micro gram/kg clonidine followed by an infusion of 0.5 micro gram [center dot] kg-1 [center dot] h-1 (group 1, n = 10) or 4 micro gram/kg followed by 1 micro gram [center dot] kg-1 [center dot] h-1 (group 2, n = 20) or 8 micro gram [center dot] kg-1 [center dot] h-1 followed by an infusion of 2 micro gram [center dot] kg-1 [center dot] h-1 (group 3, n = 20). During the operation, increases in arterial blood pressure or heart rate that did not respond to a propofol bolus (0.5 mg/kg) were treated with a bolus of intravenous lidocaine (1 mg/kg). Three successive injections were allowed. When baseline values were not restored, opioids were added and the patient was removed from the study. After operation, the clonidine infusions were maintained for 12 h. During this period and at every 30 min, sedation scores and visual analog scale values at rest and at cough were noted. In case of subjective scores up to 5 cm at rest or up to 8 cm at cough, the patients were given access to a patient-controlled analgesia device that delivered epidural bupivacaine. The end point of the study was reached once the patient activated the analgesic delivery button.

Results: During surgery, 60% of patients in group 1 compared with 33% of patients in group 2 and only 5% of patients in group 3 were removed from the study protocol because of inadequate anesthesia (P < 0.05). After operation, epidural clonidine provided complete analgesia lasting 30 +/- 21 min in group 1 compared with 251 + 237 min in group 2 or 369 +/- 256 min in group 3 (P < 0.05 for group 1 vs. groups 2 and 3 and group 2 vs. group 3).     

Epidural bupivacaine for aortic surgery The effect of dilution on the quality of analgesia

Twenty patients undergoing elective abdominal aortic aneurysm repair were randomly allocated to two groups and studied for 24 h following surgery. Postoperative analgesia was provided by epidural bupivacaine infusion and intravenous patient-controlled 0.05 mg boluses of alfentanil. One treatment group received 7 ml.h^-1 of a 0.25% solution of bupivacaine, the other 25 ml.h^-1 of a 0.07% solution. The rate of infusion was thus 17.5 mg.h^-1 in both groups. Patients receiving 7 ml.h^-1 of epidural infusate required more doses of alfentanil (median 26.5, range 0-50) than the group receiving 25 ml.h^-1 of the dilute infusion (median 3.0, range 0–16). It is concluded that 17.5 mg.h^-1 of bupivacaine infused into the epidural space produces better analgesia when infused in a volume of 25 ml.h^-1 (0.07%) than when given in a volume of 7ml.h^-1 of solution (0.25%).     

Epidural clonidine added to a bupivacaine infusion increases analgesic duration in labor without adverse maternal or fetal effects

Purpose Many obstetric patients receiving epidural analgesia are encouraged to ambulate. This current study was designed to determine the potential for maximizing the time to first epidural supplement when adding clonidine to a 0.625 mg·ml⁻¹ bupivacaine continuous epidural infusion following epidural fentanyl bolus in early labor for patients allowed to ambulate. Maternal and fetal effects secondary to clonidine were also evaluated. Methods Sixty-eight laboring primigravid women received a 3-ml epidural test dose of lidocaine with epinephrine, followed by a fentanyl 100-μg bolus (in a 10 ml-volume). The patients then received a 0.625 mg·ml⁻¹ bupivacaine continuous epidural infusion, either with or without clonidine (5 μg·ml⁻¹), at a rate of 10 ml·h⁻¹. Pain scores and side effects were recorded for each patient. Results The overall quality of analgesia was similar in both groups. The mean duration prior to request for additional analgesia was significantly longer in the clonidine group (269 ± 160 min), compared to the control group (164 ± 64 min). No patient in either group experienced any detectable motor block; one patient (clonidine group) complained of mild thigh numbness and was not allowed to ambulate. While mean blood pressure was approximately 6 mmHg lower in the clonidine group at 1, 1.5, and 3.5 h, this was not clinically significant. No adverse effects on maternal heart rate or fetal heart rate were noted. Conclusion In early laboring patients, addition of clonidine prolongs the analgesia duration of a 0.625 mg·ml⁻¹ bupivacaine continuous epidural infusion following 100 μg epidural fentanyl (after a lidocaine-epinephrine test dose) without a clinically significant increase in side effects.     

Combinations of Bupivacaine, Fentanyl, and Clonidine for Lumbar Epidural Postoperative Analgesia: A Novel Optimization Procedure

Background: The authors developed and applied a method to optimize the combination of bupivacaine, fentanyl, and clonidine for continuous postoperative lumbar epidural analgesia.

Methods: One hundred eighteen patients undergoing knee or hip surgery participated in the study. Postoperative epidural analgesia during 48 h after surgery was optimized under restrictions dictated by side effects. Initially, eight combinations of bupivacaine, fentanyl, and clonidine (expressed as drug concentration in the solution administered) were empirically chosen and investigated. To determine subsequent combinations, an optimization model was applied until three consecutive steps showed no decrease in pain score. For the first time in a clinical investigation, a regression model was applied when the optimization procedure led to combinations associated with unacceptable side effects.

Results: The authors analyzed 12 combinations with an allowed bupivacaine concentration range of 0-2.5 mg/ml, a fentanyl concentration range of 0-5 [mu]g/ml, and a clonidine concentration range of 0-5 [mu]g/ml. The best combinations of bupivacaine, fentanyl, and clonidine concentrations were 1.0 mg/ml-1.4 [mu]g/ml-0.5 [mu]g/ml, 0.9 mg/ml-3.0 [mu]g/ml-0.3 [mu]g/ml, 0.6 mg/ml-2.5 [mu]g/ml-0.8 [mu]g/ml, and 1.0 mg/ml-2.4 [mu]g/ml-1.0 [mu]g/ml, respectively, all producing a similarly low pain score. The incidence of side effects was low. The application of the regression model to combinations associated with high incidence of motor block successfully directed the optimization procedure to combinations within the therapeutic range.     

The dose-sparing effect of clonidine added to ropivacaine for labor epidural analgesia

To determine the effects of clonidine with ropivacaine during epidural labor analgesia, we studied 66 nulliparous women in early active labor. Women were randomized to receive ropivacaine 0.1% 8 mL plus 75 microg of clonidine (Group 1), ropivacaine 0.2% 8 mL plus 0.5 mL of NaCl 0.9% (Group 2), or ropivacaine 0.2% 8 mL plus 75 microg of clonidine (Group 3) 5 min after a bupivacaine 7.5 mg with epinephrine 15 microg test dose. Upon request, additional analgesia with ropivacaine 0.1% 8 mL followed by ropivacaine 0.2% 8 mL/h was administered. With clonidine, duration of analgesia was increased (132 +/- 48 min [Group 1] and 154 +/- 42 min [Group 3] versus 91 +/- 44 min [Group 2]; P < 0.05), and total ropivacaine dose over the first 4 h was significantly reduced (40.5 +/- 15 mg [Group 1] and 47.0 +/- 16 mg [Group 3] versus 72.5 +/- 18 mg [Group 2]; P < 0.01). The incidence of more profound motor block was more frequent in Group 2 (P < 0.05). Although there was a trend for more women receiving clonidine to require ephedrine for treatment of hypotension, this did not seem to have an impact on fetal outcome or incidence of cesarean deliveries for nonreassuring fetal heart rate tracings. This study demonstrates the dose-sparing effect of clonidine when added to ropivacaine. IMPLICATIONS: The effect of adding 75 microg of clonidine to ropivacaine for epidural labor analgesia was studied. Clonidine increased analgesia duration and produced dose sparing compared with ropivacaine alone. Despite a tendency for hypotension in women receiving clonidine, there was no apparent effect on delivery mode or neonatal outcome.     

Propofol and sevoflurane during epidural/general anesthesia: comparison of early recovery characteristics and pain relief

We investigated the early recovery characteristics and pain relief of adult patients during combined anesthesia with (epidural and general), either with propofol or sevoflurane for maintenance in major abdominal surgery. Twenty-two patients (ASA I-III) were enrolled in this randomized, prospective study. After fluid preloading, 10 ml of bupivacaine 0.5% + 5 ml of prilocaine 0.5% + 1 ml of fentanyl 50 microg mL(-1) were administered via an epidural catheter. General anesthesia was induced with fentanyl and propofol after T6 sensorial blockade. Propofol group (n = 11) received propofol (2-5 mg kg(-1) h(-1)), sevoflurane group (n = 11) received sevoflurane (1-2%) for maintenance. Anesthesia was supplemented with N2O in O2 and intravenous fentanyl. Continuous epidural infusion of 0.125% bupivacaine + 1 microg fentanyl (5-7 mL h(-1)) was started forty-five min after the epidural bolus dose and 5 ml of it was given at the start of the wound closure. All anesthetics were discontinued except epidural infusion during the last suture. After emergence time was determined, the patients were transferred to the PACU. They were observed for orientation times of person and place. The pain scores (verbal analogue scale, 0-10) were assessed with 30 min intervals. When the patient's pain score was >3, rescue analgesic protocol (diclofenac Na 75 mg im followed by meperidine HCI approximately 0.25 mg kg(-1) iv at the latter period) was applied. In the case of inadequate pain relief during the latter assessment periods, meperidine HCI approximately 0.25 mg kg(-1) was administered. Mann-Whitney U test and Fisher's exact test were used for the statistical analysis. A value of p<0.05 was considered significant. Between the groups no statistical differences were observed in the emergence time (5 vs. 6 min, median) and in the orientation time to person (6 vs. 10 min). Recovery of orientation to place was found faster in propofol group (7 vs. 12 min, p = 0.041). Pain scores of the patients between the groups were not statistically different at 0, 30, 60, 90, 120 min postoperatively (3, 2, 3, 2, 2, and 2, 4, 4, 3, 3, respectively). Rescue analgesic protocol and additional meperidine HCI were applied to 63.6% and 45.4% of patients in the propofol group, 54.5% and 36.3% of patients in the sevoflurane group, respectively. There weren't any statistical differences in regard to these, either. Except orientation time to place, the times of emergence and orientation to person, the pain scores and the analgesic requirements of the patients in both groups were similar. Propofol or sevoflurane did not offer any advantages for postoperative pain relief on behalf of either one when combined with epidural anesthesia.     

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

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

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

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

Prevention of phantom pain after major lower limb amputation by epidural infusion of diamorphine, clonidine and bupivacaine.

Phantom limb pain may appear in up to 85% of patients after amputation. There is no effective treatment. Perioperative epidural infusion of morphine and bupivacaine, alone or in combination, is effective in preventing phantom limb pain in patients with pre-existing limb pain. Serious side-effects, however, make them difficult to manage on a general ward. Clonidine has been shown to be an effective postoperative analgesia when applied epidurally. To mitigate the potentially serious side-effects of all these drugs, we have studied their combined efficiency in preventing phantom limb pain in a prospective controlled study of 24 patients undergoing lower limb amputation. In the study group (n = 13), an epidural infusion containing bupivacaine 75 mg, clonidine 150 micrograms and diamorphine 5 mg in 60 ml normal saline was given at 1-4 ml/h 24-48 h preoperatively and maintained for at least 3 days postoperatively. The control group (n = 11) received on-demand opioid analgesia. Pain was assessed by visual analogue scale at 7 days, 6 months and 1 year. At 1 year follow-up, one patient in the study group and eight patients in the control group had phantom pain (P < 0.002) and two patients in the study group versus eight patients in the control group had phantom limb sensation (P < 0.05). There was no significant improvement in stump pain. We conclude that perioperative epidural infusion of diamorphine, clonidine and bupivacaine is safe and effective in reducing the incidence of phantom pain after amputation.     

Mixed-effects Modeling of the Influence of Alfentanil on Propofol Pharmacokinetics

Background: The influence of alfentanil on the pharmacokinetics of propofol is poorly understood. Therefore, the authors studied the effect of a pseudo-steady state concentration of alfentanil on the pharmacokinetics of propofol.

Methods: The pharmacokinetics of propofol were studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While volunteers breathed 30% O2 in air, 1 mg/kg intravenous propofol was given in 1 min, followed by 3 mg [middle dot] kg-1 [middle dot] h-1 for 59 min (sessions A and B). During session B, a target-controlled infusion of alfentanil (target concentration, 80 ng/ml) was given from 10 min before the start until 6 h after termination of the propofol infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon dioxide were monitored. Venous blood samples for determination of the blood propofol and plasma alfentanil concentration were collected until 6 h after termination of the propofol infusion. Nonlinear mixed-effects population pharmacokinetic models examining the influence of alfentanil and hemodynamic parameters on propofol pharmacokinetics were constructed.

Results: A two-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of propofol. Alfentanil decreased the elimination clearance of propofol from 2.1 l/min to 1.9 l/min, the distribution clearance from 2.7 l/min to 2.0 l/min, and the peripheral volume of distribution from 179 l to 141 l. Scaling the pharmacokinetic parameters to cardiac output, heart rate, and plasma alfentanil concentration significantly improved the model.     

A comparison of spinal and epidural anaesthesia for hip arthroplasty

Spinal and epidural anaesthesia were compared in 65 patients undergoing hip arthroplasty, with regard to the degree of sensory and motor blockade, cardiovascular effects, operating conditions, the dose of propofol required to produce satisfactory hypnosis, and complications. Epidural anaesthesia was successful in 30 patients using an initial dose of 15 ml of 0.5% bupivacaine, and spinal anaesthesia in 32 patients, using 4 ml 0.5% isobaric bupivacaine. The two techniques were similar with regard to the level of sensory blockade (T8), degree of hypotension and perioperative haemorrhage. Differences occurred in the degree of motor blockade (mean Bromage score of 1 in the spinal group vs 3.86 in the epidural group) (P less than 0.05), time to achieve maximal cephalad spread (13 min in the spinal group vs 21 min in the epidural group) (P less than 0.05) and the dose of propofol required to produce adequate hypnosis (1.95 mg.kg-1.hr-1 in the spinal group vs 2.89 mg.kg-1.hr-1 in the epidural group) (P less than 0.05). Only seven patients required urethral catheterization in this spinal group compared with 14 in the epidural group (P less than 0.05). Spinal anaesthesia also proved advantageous by providing better operating conditions for the surgeon, with a lower incidence of patient movement.     

The effect of epidural bupivacaine on induction and maintenance doses of propofol (evaluated by bispectral index) and maintenance doses of fentanyl and vecuronium

The growing interest in combining local and general anesthesia has led to studies investigating possible interactions between general anesthesia and local anesthetics administered via spinal, epidural, IV, or IM routes. However, no study has evaluated the effect of local anesthetics on all three components of balanced anesthesia, i.e., hypnosis, analgesia, and muscle relaxation. In this prospective, randomized, double-blind study, we investigated the effect of epidural bupivacaine on the dose requirement of propofol (as evaluated by using the bispectral index [BIS]), fentanyl, and vecuronium for general anesthesia. This study consisted of 30 adults, ASA physical status I and II, undergoing Whipple's pancreaticoduodenectomy for periampullary carcinoma lasting >4 h. An epidural catheter was placed between T9-10. Depending on the group allocation, 10 mL of the study drug was administered as a bolus followed by an infusion at 6 mL/h via the epidural catheter. Patients were divided into 2 groups of 15 each. Patients in the control group received epidural normal saline whereas those in the bupivacaine group received epidural bupivacaine 0.1%. Induction of anesthesia was performed with IV fentanyl 2 mug/kg and propofol titrated to achieve BIS between 40-50. Endotracheal intubation was facilitated by the IV administration of vecuronium 0.1 mg/kg and patient's lungs were ventilated with 66% nitrous oxide in oxygen. After intubation, infusion of propofol 1% was titrated to maintain BIS between 40-50. Inadequate analgesia was defined as an increase in systolic blood pressure and/or heart rate by >20% of baseline values in response to surgical stimulus and was treated with bolus fentanyl 0.5 mug/kg. Neuromuscular monitoring was used to assess the need for additional doses of vecuronium. Data were analyzed by using the Student's t-test and P 相似文献   

Ornipressin (Por 8): An efficient alternative to counteract hypotension during combined general/epidural anesthesia

We sought to evaluate the efficacy and side effect profile of a small dose of ornipressin, a vasopressin agonist specific for the V1 receptor, administered to reverse the hypotension associated with combined general/epidural anesthesia. A total of 60 patients undergoing intestinal surgery were studied. After the induction of anesthesia, 7-8 mL of bupivacaine 0.5% with 2 microg/kg clonidine and 0.05 microg/kg sufentanil after an infusion of 5 mL of bupivacaine 0.06% with 0.5 microg x kg(-1) x h(-1) clonidine and 0.1 microg/h of sufentanil were administered by an epidural catheter placed at T7-8 vertebral interspace. When 20% reduction of baseline arterial blood pressure developed, patients were randomly assigned to receive, in a double-blinded design, dopamine started at 2 microg x kg(-1) x min(-1), norepinephrine started at 0.04 microg x kg(-1) x min(-1), or ornipressin started at 1 IU/h. Fifteen patients presenting without hypotension were used as control subjects. Beside routine monitoring, S-T segment analysis, arterial lactacidemia, and gastric tonometry were performed. Ornipressin restored arterial blood pressure after 8 +/- 2 vs 7 +/- 3 min in the norepinephrine group and 11 +/- 3 min in the dopamine group (P < 0.05). This effect was achieved with 2 IU/h of ornipressin in most of the patients (11 of 15). Ornipressin did not induce any modification of the S-T segment; however, it significantly increased intracellular gastric PCO(2) (P < 0.05), indicating splanchnic vasoconstriction. Implications: In the population studied, small-dose ornipressin was effective to restore arterial blood pressure without causing major ischemic side effects.     

Patient supplemented epidural analgesia after major abdominal surgery with bupivacaine/fentanyl or ropivacaine/fentanyl

PURPOSE: To compare analgesic efficacy and occurrence of motor block and other side effects during patient supplemented epidural analgesia (PSEA) with either ropivacaine/fentanyl or bupivacaine/fentanyl mixtures. METHODS: In a prospective, randomized, double-blind study, 32 ASAI-III patients undergoing major abdominal surgery received an epidural catheter at the T8- T10, followed by integrated general epidural anesthesia. Postoperative epidural analgesia was provided using a patient controlled pump with either ropivacaine 0.2%/2 microg x ml(-1) fentanyl (group Ropivacaine, n = 16) or bupivacaine 0.125%/2 microg x ml(-1) fentanyl (group Bupivacaine, n = 16) [background infusion 4-6 ml x hr(-1), 1.5 ml Incremental Doses and 20 min lock out]. Verbal pain rating score, number of incremental doses, consumption of epidural analgesic solution and rescue analgesics, sedation (four-point scale), and pulse oximetry were recorded by a blind observer for 48 hr after surgery. RESULTS: No differences in pain relief, motor block, degree of sedation, pulse oximetry and other side effects were observed between the two groups. The number of incremental doses and the volume of analgesic solution infused epidurally were higher in patients receiving the bupivacaine/fentanyl mixture (10 [0-52] I.D. and 236 [204-340] ml) than in patients receiving the ropivacaine/fentanyl solution (5 [0-50] I.D. and 208 [148-260] ml) (P = 0.03 and P = 0.05, respectively). CONCLUSION: Using a ropivacaine 0.2%/2 microg x ml(-1) fentanyl mixture for patient supplemented epidural analgesia after major abdominal surgery provided similar successful pain relief as bupivacaine 0.125%/2 microg x ml(-1) fentanyl, but patients receiving bupivacaine/fentanyl requested more supplemental.     

Oral clonidine premedication reduces induction dose and prolongs awakening time from propofol-nitrous oxide anesthesia

PURPOSE: To evaluate whether oral clonidine premedication affects the induction dose of propofol and awakening time from epidural and propofol anesthesia. METHODS: Thirty-nine female patients (ASA I or II) were randomly allocated to receive 5 microg x kg(-1) clonidine p.o. or no clonidine 90 min before induction of anesthesia. After epidural anesthesia was achieved with lidocaine, general anesthesia was induced with continuous i.v. infusion of propofol at a rate of 50 mg x min(-1) until loss of eyelash reflex and responses to verbal commands, which were judged by a blinded observer. After a laryngeal mask airway was inserted, anesthesia was maintained with N2O 67%, O2 33% and propofol adjusted to maintain hemodynamic stability. After completion of surgery, a blinded observer recorded the time from discontinuance of propofol and N2O until the patient was awake and responsive (awakening time), and then, the laryngeal mask airway was removed. RESULTS: The induction dose of propofol in the clonidine group (1.4 +/- 0.3 mg) was less than that in the control group (1.9 +/- 0.4 mg, P < 0.05), while the awakening time of the clonidine group (470 +/- 145 sec) was longer than that of the control group (329 +/- 123 sec, P < 0.05). CONCLUSION: Premedication with 5 microg x kg(-1) clonidine p.o. reduced the induction dose of propofol, but delayed emergence from propofol anesthesia.     

Effect of Diltiazem on Midazolam and Alfentanil Disposition in Patients Undergoing Coronary Artery Bypass Grafting

Background: Midazolam and alfentanil are desirable anesthetic adjuncts for cardiac anesthesia. They are metabolized by cytochrome P450 3A (CYP3A) enzymes. These isozymes are inhibited by concurrent medications, including the calcium channel antagonist diltiazem, which may have an effect on recovery from anesthesia.

Methods: Thirty patients having coronary artery bypass grafting were randomly assigned to receive either diltiazem (60 mg orally 2 h before induction of anesthesia and an infusion of 0.1 mg [centered dot] kg sup -1 [centered dot] h sup -1 started at induction and continued for 23 h) or placebo in a double-blind study. Anesthesia was induced with 0.1 mg/kg midazolam, 50 micro gram/kg alfentanil, and 20 to 80 mg propofol and maintained with infusions of 1 micro gram [centered dot] kg sup -1 [centered dot] min sup -1 of both midazolam and alfentanil supplemented with isoflurane. Plasma midazolam and alfentanil concentrations and areas under the plasma concentration-time curves were determined. The terminal half-life and the time for the drug plasma level to decrease 50% after cessation of the infusion (t50) were calculated for midazolam and alfentanil. Separation from mechanical ventilation and tracheal extubation were performed according to the study protocol.

Results: Diltiazem increased the mean concentration-time curves (from end of anesthesia until 23 h) of midazolam by 24% (P < 0.05) and that of alfentanil by 40% (P < 0.05). The mean half-life of midazolam was 43% (P < 0.05) and that of alfentanil was 50% (P < 0.05) longer in patients receiving diltiazem. The mean t50 of alfentanil was 40% longer (P <0.05) in patients receiving diltiazem, but the change in the mean t50 of midazolam (25%) was not statistically significant. In patients receiving diltiazem, tracheal extubation was performed on average 2.5 h later (P = 0.054) than in those receiving placebo.     

The effect of alfentanil versus ketamine on the intubation condition and hemodynamics with low-dose rocuronium in children

Purpose

We investigated the effect of alfentanil and ketamine on the intubation condition and hemodynamic parameters during propofol anesthesia with low-dose rocuronium in children.

Methods

Fifty-four children, aged 3–9 years undergoing tonsillectomy, were randomly allocated to receive either alfentanil 20 μg/kg (alfentanil group, n = 27) or ketamine 0.5 mg/kg (ketamine group, n = 27) 1 min before anesthesia induction. Anesthesia was induced with propofol 2.5 mg/kg and rocuronium 0.3 mg/kg and maintained with propofol infusion (6 mg/kg/h). The neuromuscular relaxation was monitored, and intubation conditions, hemodynamic changes, and recovery time were assessed.

Results

All patients were successfully intubated and there were no significant differences in the intubation conditions between alfentanil and ketamine groups. At the time of tracheal intubation, the median [inter-quartile range] twitch height was similar between two groups (37 [4–48] % in the alfentanil group vs. 29 [4–43.5] % in the ketamine group, p = 0.326).

Conclusions

This study showed that both ketamine 0.5 mg/kg and alfentanil 20 μg/kg provided adequate intubation condition during propofol induction with low-dose rocuronium in children. The mean arterial pressure and heart rate were higher in the ketamine group after propofol injection but they remained within the normal limit in both groups throughout the study period.     

Patient-controlled epidural analgesia after major urologic surgeries. A comparison of tramadol with or without bupivacaine

The efficiency and safety of patient-controlled epidural analgesia by using tramadol alone and combined with bupivacaine were investigated for postoperative pain treatment after major urological surgeries. For PCEA: in group I (n = 17) a loading dose of 20 mg tramadol with a continuous infusion of 1 mg/ml tramadol at a rate of 8 ml/h was given. In group II (n = 17), patients received an initial loading dose of 20 ml bupivacaine 0.125% and a supplemental continuous infusion of 8 ml/h. In group III (n = 17), a loading dose of 20 mg tramadol with 20 ml bupivacaine 0.125% were given and a supplemental infusion of 1 mg/ml tramadol in 20 ml bupivacaine 0.125% combination was begun with a rate of 8 ml/h. A demand epidural bolus dose of 5 ml with a lockout time of 30 min was also used in all patients. VAS for pain intensity, vital signs, sedation scale and side effects was monitored at 0, 15, 30 min and 1, 2, 3, 4, 8, 12, and 24 h of the postoperative period. Statistical significance was determined using Kruskal-Wallis, Fisher's exact, analysis of variance for repeated measurements and Tukey tests. The hemodynamic values and sedation scales were insignificantly different (p > 0.05). The adequate analgesia was provided in all patients. However VAS values were significantly lower in group III than in groups I and II at every measurement (p < 0.05). The incidence of side effects in all three groups was low (p > 0.05). In conclusion, we suggested that a combination of tramadol with bupivacaine can provide the most effective and safe postoperative analgesia with minimal risk for side effects.     

The effect of epidural bupivacaine on vecuronium–induced neuromuscular blockade in children

The efTect of epidural bupivacaine on potency and duration of action of vecuronium–induced neuromuscular blockade (NMB) was evaluated in 30 general surgical paediatric patients (ASA I–II) of three to ten years of age. Premedication was midazolam 0.5 μg kg^-1 orally (max 15 mg). In addition to general anaesthesia, 15 of the children received a lumbar epidural block with 0.5% bupivacaine 2.5 mg kg^-1. Anaesthesia was induced and maintained with N₂O:o₂ (2:1), propofol and alfentanil. NMB was monitored by adductor pollicis EMG with the train–of–four stimulus every 20 sec. Thirty minutes following the epidural bupivacaine injection (mean plasma concentration 0.86 μg ml^-1) or induction of anaesthesia a cumulative dose–response curve of vecuronium was established to achieve a 95% depression of the twitch response. Thereafter, NMB was allowed to recover spontaneously. ED doses of vecuronium were 19–22% greater in the control group than in the epidural group. ED^ doses were 33.8 (s.e.mean 1.3) μg kg"¹ and 28.4 (2.2) μg kg"', respectively ( P <0.05). There were no differences in recovery times from NMB between control and epidural group, the recovery index (time of twitch height to recover from 25 to 75%) being 6.4 (0.4) min and 7.0 (0.9) min, respectively. However, a negative correlation was found between bupivacaine plasma concentration and an ED₅₀ dose of vecuronium ( P =0.01). Our results indicate that vecuronium is slightly more potent in children with bupivacaine epidural block than in children without it.     

Analgesia for circumcision in a paediatric population: comparison of caudal bupivacaine alone with bupivacaine plus two doses of clonidine

BACKGROUND: Clonidine is often used to improve the duration and quality of analgesia produced by caudal epidural blockade, although the optimum dose of clonidine with bupivacaine remains uncertain. Methods: We compared the effect of clonidine, 1 and 2 microg x kg(-1), added to bupivacaine (1.25 mg x kg(-1)) with that of bupivacaine alone in 75 male children undergoing elective circumcision. RESULTS: There was a trend towards increasing duration of analgesia with increasing dose of clonidine [group B (bupivacaine) 280.7 (171.6) min, C1 (bupivacaine + clonidine 1 microg x kg(-1)) 327.8 (188.3) min and C2 (bupivacaine + clonidine 2 microg x kg(-1)) 382.0 (200.6) min], although this difference was not statistically significant. Mean time to arousal from anaesthesia was significantly prolonged with clonidine 2 microg kg(-1) (group C2 21.3 (13-36) min, group C1 14.0 (6-25) min and group B 14.4 (2-32) min. Supplementary analgesic requirements and incidence of adverse effects were low, with no differences between the groups. Conclusions: For paediatric circumcision, under general anaesthesia, the addition of clonidine 2 microg x kg(-1) to low volume (0.5 ml x kg(-1)) caudal anaesthetics has a limited clinical benefit for children undergoing circumcision.