Schizophrenia and the dopamine-beta-hydroxylase gene: results of a linkage and association study

PURPOSE: A dose-finding study to investigate the use of epidural infusions of ropivacaine for postoperative analgesia following orthopaedic surgery. METHODS: This was a randomized, double-blind study. Surgery was performed using a combination of a lumbar epidural block utilizing ropivacaine 0.5% and a standardized general anaesthetic. Postoperatively, an epidural infusion of the study solution (saline, ropivacaine 0.1%, 0.2% or 0.3%) was started at the rate of 10 ml.hr-1 and continued for 21 hr after arrival in the PACU. Analgesia was supplemented with PCA morphine (dose = 1.0 mg, lock-out = 5 min). RESULTS: Forty-four patients completed the study. The ropivacaine 0.1%, 0.2%, 0.3% groups required less morphine over the 21 hr than the saline group (P < 0.01). The VAS pain scores were also lower in the three ropivacaine groups (P < 0.001). The ropivacaine groups maintained sensory anaesthesia to pinprick when compared with saline (P < 0.05). The motor block in the 0.3% group was significantly higher than the saline group at all times (P < 0.05), and higher than the 0.1% group at eight hours (P < 0.01), while the 0.2% group had higher Bromage scores than saline at 4 and 21 hr (P < 0.05). CONCLUSIONS: The use of continuous epidural infusions of ropivacaine 0.1%, 0.2% and 0.3% at 10 ml.hr-1 improved postoperative pain relief and decreased PCA morphine requirements in patients undergoing major orthopaedic surgery. The 0.1% and 0.2% concentrations produced similar sensory anaesthesia with less motor blockade than the 0.3% concentration.     

Postoperative patient-controlled epidural analgesia with opioid bupivacaine mixtures

PURPOSE: To determine the efficacy and safety of patient-controlled epidural analgesia of morphine or fentanyl in combination with bupivacaine for postoperative pain relief. METHODS: Forty ASA I-II patients scheduled for major abdominal surgery were studied. After insertion of a lumbar epidural catheter, patients were given a non-opioid general anaesthetic. After surgery patients complaining of pain, received a loading dose of 2 mg morphine (Group I) or 50 micrograms fentanyl (Group II). For continuing pain, 1 mg morphine in 4 ml bupivacaine 0.125% (0.25 mg.ml-1 morphine and 1 mg.ml-1 bupivacaine, Group I) or 20 micrograms fentanyl in 4 ml bupivacaine 0.125% (5 micrograms.ml-1 fentanyl and 1 mg.ml-1 bupivacaine Group II) were administered. Blood pressure, heart rate, respiratory rate and SpO2 were monitored. Assessments of pain (VAS), nausea-vomiting, motor block, pruritus and sedation were recorded for 24 hr. RESULTS: No difference in pain or sedation was observed between groups. The 24 hr postoperative opioid consumption was 15.50 +/- 7.53 mg morphine and 555.10 +/- 183.85 micrograms fentanyl. Total bupivacaine 0.125% consumption was 58.00 +/- 30.14 ml in Group I and 101.05 +/- 36.77 ml in Group II. One patient in Group II complained of motor weakness in one leg. The incidence of nausea (Group I 45%, Group II 10% P < 0.05) and pruritus (Group I 30%, Group II 5% P < 0.05) was less in patients receiving fentanyl. CONCLUSION: Both methods were effective in the prevention of pain but, because of fewer side effects, fentanyl may be preferable to morphine.     

Caudal clonidine and bupivacaine for combined epidural and general anaesthesia in children

BACKGROUND: Clonidine produces analgesia by actions on alpha 2-adrenoceptors and enhances both sensory and motor blockade from epidural injection of local anaesthetics. Low-dose clonidine has been used so far for caudal injection in children. Our aim was to study the perioperative effects of high-dose caudal clonidine when added to low concentration of bupivacaine for combined epidural and general anaesthesia in children. METHODS: After induction of general anaesthesia caudal block was performed either with 1 ml.kg-1 bupivacaine 0.175% with the addition of clonidine 5 micrograms.kg-1 (n = 20), or with 1 ml.kg-1 bupivacaine 0.175% (n = 20). The intraoperative anaesthetic requirements, the perioperative haemodynamic effects, respiratory rate, sedation score, postoperative pain scores and side effects were assessed by a blinded observer. A patient-controlled analgesia system was used for postoperative pain relief. The quality of postoperative pain relief was assessed using Smiley's pain analogue scale. RESULTS: Intraoperative haemodynamic responses did not differ between the groups. However, during emergence from general anaesthesia children in the clonidine group had significantly lower heart rates and blood pressure compared to children in the control group. In addition, heart rates and blood pressures were also lower in the clonidine group in the early postoperative period (P < 0.05). Postoperative analgesia was significantly better in the clonidine group as evidenced by the total number of requests (3 vs 12, P < 0.05) and the total amount of tramadol (20.5 mg vs 72.8 mg, P < 0.05) administered. The duration of the caudal analgesia was significantly longer in the clonidine group (20.9 +/- 7.4 h vs 14.4 +/- 10.9 h, P < 0.05). CONCLUSION: Our results suggest that caudal clonidine 5 micrograms.kg-1 enhances and prolongs caudal blockade with bupivacaine (1.175% in children. It also blocks sympathoadrenergic responses during emergence from anaesthesia. Sedation and cardiovascular effects are observed up to 3 h into the postoperative period.     

Postoperative analgesia after co-administration of clonidine and morphine by the intrathecal route in patients undergoing hip replacement

Postoperative analgesia after intrathecal co-administration of clonidine hydrochloride (75 micrograms) and morphine sulfate (0.5 mg) was compared with analgesia produced after either intrathecal morphine (0.5 mg) or 0.9% sodium chloride in 90 patients undergoing total hip replacement under bupivacaine spinal anesthesia. Patient-controlled morphine requirements were significantly reduced (P < 0.001) postoperation by both clonidine/morphine (median 5 mg/24 h) and morphine (median 7 mg/24 h) compared with control (saline) (median 28 mg/24 h). However, no significant additional reduction in postoperative analgesic requirements was shown with the clonidine/morphine combination compared with morphine alone. Visual analog pain scores, although good in all groups at all times, were significantly poorer in the control group at 2 h (P < 0.04) and 4 h (P < 0.001) after operation compared with both treatment groups, and significantly poorer than the clonidine/morphine group at 6 h (P < 0.002) and 24 h (P < 0.009) postoperation. Mean arterial blood pressure was significantly lower in the clonidine/morphine group than in the two other groups (P < 0.001) between 2 and 5 h after operation. The incidence of emesis was similar in the clonidine/morphine and morphine groups and was significantly more than in the control group.     

Survival after massive ecstasy overdose

This study was designed to evaluate the potential advantages of combined epidural and light general anesthesia over the commonly employed general anesthesia during open heart surgery. Twenty-four patients undergoing mitral valve replacement were thus studied. General anesthesia was maintained with an isoflurane-nitrous oxide-oxygen was mixture and morphine sulfate (0.4 mg/kg i.v. initially) followed by postoperative pain control with morphine in 12 patients (group GA). The remaining 12 patients (group EAA) received continuous epidural bupivacaine (0.125%)-morphine (50 micrograms/ml) supplemented with the same gas mixture as group GA. Epidural infusion was continued until the third postoperative day. Changes in the serum cortisol and beta-endorphin levels together with postoperative pain relief defined as good (scale 0-2), fair (3-4), or poor (5-10) were observed serially. Lower cortisol levels were observed in group EAA than in group GA (P < 0.05) just before skin closure, on the second and the third postoperative day. The beta-endorphin levels were substantially lower in group EAA than in group GA throughout the observation. The pain scores were good in 2 patients (17%), fair in 6 (50%), and poor in 4 (33%) for group GA, and good in 8 (67%), fair in 3 (25%), and poor in 1 (8%) for group EAA. We thus conclude that a combined epidural and light general anesthesia is considered to attenuate the stress response and thereby provides a better quality of postoperative pain control.     

Multicomponent intravenous and epidural anesthesia in aorto-coronary bypass surgery

The influence of epidural anesthesia (CEA) on clinical manifestations, cortisole and adrenocorticotropic hormone (ACTH) level, central hemodynamic values during aorto-coronary bypass surgery (ACBS) in 56 patients aged 42-68 years with preserved functional capacity of the myocardium was studied. Catheterisation of the epidural space was carried out in the evening before the operation according to the standard method at the level of T4-T5 with the use of disposable epidural set. During the procedure before perfusion 2% solution of lidocaine 3.8 +/- 0.2 mg/kg was introduced in epidural space (taking into account test-dose) as a bolus in 3-4 motions. The dose of local anesthetics for infusion was selected separately for each individual case with due regard for hemodynamic values. During artificial circulation additionally local anesthetic was introduced as a bolus, the dose being 4.7 +/- 0.8 mg/kg. At the end of the operation morphine (0.061 +/- 0.001 mg/kg) was introduced. It was established that combined application of intravenous and epidural anesthesia represents highly effective method of anesthesia in aorto-coronary bypass surgery. According to clinical course data, cortisone and ACTH blood contents and hemodynamic parameters, EA provides adequate anesthesia, promotes stabilization of hemodynamic values and creates functionally more advantageous conditions for the myocardium in patients with CHD during aorto-coronary bypass operation. Anesthesiologic aid with the use of EA promotes reduction of intravenous anesthetics expenditure, earlier waking up of the patients in postoperative period and decrease in duration of postoperative artificial lung ventilation.     

Diagnosis of trypanosomiasis in experimental mice and field-infected camels by detection of antibody to trypanosome tyrosine aminotransferase

We designed this double-blind study to evaluate the effect of adding small-dose ketamine in a multimodal regimen of postoperative patient-controlled epidural analgesia (PCEA). Ninety-one patients, ASA physical status I-III, undergoing major surgery, received a standardized general anesthesia and epidural catheterization in an appropriate intervertebral space after surgery. A PCEA device was programmed to deliver a regimen of morphine 0.02 mg/mL, bupivacaine 0.8 mg/mL, and epinephrine 4 microg/mL, with the addition of ketamine 0.4 mg/mL (ketamine, n = 45) or without (control, n = 46). The mean visual analog pain scale (VAS) scores during cough or movement for the first 3 days after surgery were higher in the control group than in the ketamine group (P < 0.05), whereas the mean VAS score at rest for the first 2 days were higher in the control group than in the ketamine group (P < 0.05). Furthermore, patients in the control group consumed more multimodal analgesics than patients in the ketamine group for the first 2 days (P < 0.05). The sedation scores and the incidence of side effects (pruritus, nausea, emesis, sleep deprivation, motor block, and respiration depression) were similar between the two groups. We conclude that adding ketamine 0.4 mg/mL in a multimodal PCEA regimen provides better postoperative pain relief and decreases consumption of analgesics. Implications: Many studies have evaluated one or a combination of two analgesics for postoperative pain control, but few have examined a multimodal approach using three or four different epidural analgesics. This study demonstrates an additive analgesic effect when ketamine is added to a multimodal analgesic treatment.     

Measurement of cerebral venous oxyhemoglobin saturation in children by near-infrared spectroscopy and partial jugular venous occlusion

Surgery of the anterior cruciate ligament causes severe postoperative pain. This study aimed to compare efficacy and side effects of two postoperative analgesia methods, during 24 hours. Twenty healthy patients were assigned to two groups (n = 10): the patients of the first group were given by an epidural catheter 3 mg of morphine hydrochloride, every twelve hours. The patients of the second group received 2 mg h-1 of intravenous nalbuphine. The degree of pain was studied with a visual analogue scale. After the third postoperative hour, it was significantly higher in the second group, but the nalbuphine dose was low. The incidence of respiratory depression, nausea, pruritus was not statistically different between the groups, but 7/10 patients in the first group suffered of urinary retention (the first micturition was obtained 10.5 hours after the end of surgery in the first group and 5.3 h in the second one). Two patients needed an uretral catheter. These results might tend to show a greater efficactly of epidural morphine, with a higher incidence of urinary side effects.     

Postoperative epidural infusion of morphine and bupivacaine is safe on surgical wards. Organisation of the treatment, effects and side-effects in 2000 consecutive patients

BACKGROUND: There was an obvious need to improve the quality and safety of our postoperative pain treatment and to introduce an improved routine service on surgical wards. METHODS: It was decided to use postoperative epidural infusion of morphine 0.04 mg/ml and bupivacaine 2.5 mg/ml (0.25%) 4-8 ml/h as pain relief after major surgery. An education programme was run emphasising the benefits, side-effects and the importance of regular monitoring of pain intensity, vital functions (respiratory rate, blood pressure, heart rate), motor function of the legs and the need for additional drugs in order to detect side-effects as well as lack of adequate analgesic effect. A detailed observation sheet was used collecting information every 2 h throughout the epidural treatment period in order to secure monitoring and adjustment of the treatment. Close contact was maintained with the wards. RESULTS: We present a detailed analysis of our first 2000 postoperative patients, mainly after orthopaedic (46.1%), gastrointestinal (32.0%), urologic (8.7%) and vascular (8.5%) surgery. Duration of the treatment was less than 24 h in 41.4% and more than 48 h in 29.7%. Pain relief was adequate in most patients, best after vascular surgery in the lower extremities (mean VAS 0.15/10.0 (95% confidence interval 0.09-0.23)) and less after gastrointestinal (mean VAS 0.49/10 (0.43-0.54)) and thoracic surgery (mean VAS 0.59/10 (0.38-0.81)). The infusion was stopped due to respiratory depression in 3 patients (0.15%). Four (0.2%) had systolic blood pressure < 80 mmHg and had to be treated with vasopressors. A total of 56 (2.8%) patients were considered to be problem patients due to excessive sedation (0.4%), hypotension (0.7%), respiratory depression (1.6%) or lower extremity paralysis (0.05%). All patients had urinary catheter until 6 h after termination of the epidural treatment. One patient had the epidural catheter accidentally placed subarachnoidally and experienced severe respiratory depression. No permanent sequelae were recorded in the postoperative patients, but 2 traumatised patients developed epidural abscesses after 3 weeks of treatment, which resulted in lower extremity paralysis. Late response to the warning signs might have contributed to the irreversible paraplegia. CONCLUSION: Our experience with this postoperative epidural analgesia regime is favourable. It has been easy to administer and monitor. Pain relief was excellent, side-effects were few and picked up by the established routines followed by the ward staff except in the 2 trauma patients who developed epidural abscesses. The staff on the surgical wards were motivated for this kind of work. Education and strict surveillance routines are mandatory in order to secure prompt action when warning signs develops (e.g. lower limb paralysis).     

Influence of dose and timing of administration of morphine on postoperative pain and analgesic requirements

In a randomized, double-blind study, we have investigated the effect of dose and timing of administration of morphine on postoperative pain and analgesic requirements in 60 patients undergoing hysterectomy, with or without salpingo-oophorectomy. Patients were allocated randomly to one of three groups: during standardized general anaesthesia, group post received morphine 0.15 mg kg-1 i.v. at peritoneal closure after hysterectomy; group pre-low received morphine 0.15 mg kg-1 on induction of anaesthesia; and group pre-high received morphine 0.3 mg kg-1 on induction of anaesthesia. Median postoperative morphine consumption (first 24 h) from a PCA system was 68 mg (group post), 56 mg (group pre-low) and 43 mg (group pre-high), and total perioperative morphine consumption (induction of anaesthesia to end of 24 h after surgery) was 77 mg (group post), 65 mg (group pre-low) and 63 mg (group pre-high). Pain scores (at rest and on movement) were similar in the three groups. A large dose of morphine 0.3 mg kg-1 i.v. on induction of anaesthesia significantly reduced postoperative PCA morphine requirements compared with the smaller dose (0.15 mg kg-1) administered at induction or peritoneal closure, in patients undergoing hysterectomy, with or without salpingo-oophorectomy.     

Long-term bone marrow culture profiles in patients with myelodysplastic syndromes are not explicable by defective apoptosis

PURPOSE: To compare intraoperative anaesthetic and haemodynamic effects of clonidine-bupivacaine, morphine-bupivacaine and placebo-bupivacaine combinations during continuous spinal anaesthesia. METHODS: Thirty six geriatric patients, undergoing knee replacement using continuous spinal anaesthesia were randomly assigned to: Placebo (n = 12), clonidine (n = 12) and morphine (n = 12), where 1 ml saline, 0.15 mg clonidine or 0.15 mg morphine were mixed with 10 mg bupivacaine 0.5%. Anaesthetic variables studied were maximal sensory level and degree of motor block, duration of surgical analgesia and duration of anaesthesia. Changes in systolic arterial pressure and vasopressor requirements were evaluated. RESULTS: Maximal sensory level and degree of motor block were comparable among the groups. Before surgery two patients in the placebo group, three in the clonidine and one in the morphine group received one additional ml bupivacaine 0.5% because of inadequate anaesthesia and were not considered for determination of duration of surgical analgesia. In the remainder, 1/9 in the clonidine group, 8/10 in placebo and 8/11 in morphine (P < 0.05) received reinjection of bupivacaine for surgical pain. These injections were given about 2 1/2 hr after the initial intrathecal injection, the duration of anaesthesia being about four hours. During the first 30 min after the initial injection the decrease in systolic pressure was greater in the clonidine and morphine than in the placebo group (P < 0.05). Thereafter, vasopressor requirements were higher only in the clonidine group (P < 0.05). CONCLUSION: In elderly patients 0.15 mg clonidine but not 0.15 mg morphine prolonged surgical analgesia when added to 10 mg plain bupivacaine.     

High-Resolution Infrared Fourier-Transform Spectroscopy and Rotational Constants of the nu4 Band of BrNO2

In this study, we assessed the influence of three analgesic techniques on postoperative knee rehabilitation after total knee arthroplasty (TKA). Forty-five patients scheduled for elective TKA under general anesthesia were randomly divided into three groups. Postoperative analgesia was provided with i.v. patient-controlled analgesia (PCA) with morphine in Group A, continuous 3-in-1 block in Group B, and epidural analgesia in Group C. Immediately after surgery, the three groups started identical physical therapy regimens. Pain scores, supplemental analgesia, side effects, degree of maximal knee flexion, day of first walk, and duration of hospital stay were recorded. Patients in Groups B and C reported significantly lower pain scores than those in Group A. Supplemental analgesia was comparable in the three groups. Compared with Groups A and C, a significantly lower incidence of side effects was noted in Group B. Significantly better knee flexion (until 6 wk after surgery), faster ambulation, and shorter hospital stay were noted in Groups B and C. However, these benefits did not affect outcome at 3 mo. We conclude that, after TKA, continuous 3-in-1 block and epidural analgesia provide better pain relief and faster knee rehabilitation than i.v. PCA with morphine. Because it induces fewer side effects, continuous 3-in-1 block should be considered the technique of choice. Implications: In this study, we determined that, after total knee arthroplasty, loco-regional analgesic techniques (epidural analgesia or continuous 3-in-1 block) provide better pain relief and faster postoperative knee rehabilitation than i.v. patient-controlled analgesia with morphine. Because it causes fewer side effects than epidural analgesia, continuous 3-in-1 block is the technique of choice.     

Comparative study of preemptive and postincisional lumbar epidural morphine in pulmonary resection. Preliminary report

OBJECTIVES: To evaluate the efficacy and incidence of side effects of two types of lumbar epidural analgesia with morphine, preemptive or postincisional, combined with total intravenous anesthesia in chest surgery. PATIENTS AND METHODS: This double-blind prospective study enrolled 20 patients (ASA I-IV) undergoing lobectomy or pneumonectomy. Anesthetic induction and maintenance was provided with propofol, atracurium and alfentanil. Lumbar epidural analgesia (L2-L3) with morphine was provided for group A patients with 2 to 4 mg upon excision of tissue and for group B with 2 to 4 mg during anesthetic induction. The following variables were recorded: arterial blood gas concentrations, heart rate, SpO2, EtCO2, postanesthetic recovery, arterial gases, side effects and pain on a visual analogue scale. Top-up analgesia was provided by intravenous metamizole and/or epidural morphine. For statistical analysis we used ANOVA, chi-square tests and Student-Newman-Keuls tests. RESULTS: The need for propofol and alfentanil during anesthesia, and for morphine and metamizole after surgery were statistically greater in group A. Pain 18 hours after surgery was also greater in group A. No significant differences between groups for other variables was observed. CONCLUSIONS: Preemptive analgesia with lumbar epidural morphine in addition to the general anesthesia described here seems to provide higher-quality analgesia with few side effects, reducing the need for propofol and alfentanil during surgery and for postoperative morphine and metamizole.     

Evaluation of the safety and efficacy of ketorolac versus morphine by patient-controlled analgesia for postoperative pain

STUDY OBJECTIVE: To compare ketorolac tromethamine with morphine for pain management after major abdominal surgery. DESIGN: Double-blind, randomized study. SETTING: Hospital recovery room and postoperative surgical unit. PATIENTS: One hundred ninety-one patients with at least moderate pain after major abdominal surgery. INTERVENTIONS: Patients received ketorolac by patient-controlled analgesia (PCA) bolus alone (Ket B), ketorolac by bolus plus infusion (Ket I), or morphine by PCA bolus (morphine), with injectable morphine available for supplementation. MEASUREMENTS AND MAIN RESULTS: Levels of sedation, pain intensity, pain relief, and adverse events were recorded at baseline, at 2, 4, and 6 hours, and at termination. Supplemental morphine was required by 71% of Ket B patients, 67% of Ket I patients, and 38% of morphine patients (p < or = 0.001 for Ket B vs morphine). Although patients receiving ketorolac required more supplemental morphine than the morphine group (6.0 mg Ket I, 6.2 mg Ket B, 4.0 mg morphine), there was a large morphine-sparing effect in both ketorolac groups (total morphine 6.0 mg Ket I, 6.2 mg Ket B, 33.3 mg morphine). Overall pain relief scores were similar for morphine and Ket I groups, and were lower for Ket B than for morphine (p = 0.002). There were no differences among groups in numbers of patients with adverse events. CONCLUSION: Ketorolac may be effective when administered by PCA device, and has a clear morphine-sparing effect.     

Dose-response relationship of clonidine with epidural administration of ropivacaine in orthopedic procedures of the lower extremities

OBJECTIVE: The aim of this study was to investigate preliminarydose-range effects of clonidine added to ropivacaine for epidural analgesia in elective orthopedic surgery of the lower limbs with doses, causing a minimum of cardiovascular side effects. METHODS: 60 patients were randomly assigned to receive in a double-blind fashion a mixture of 1 mg/cm height ropivacaine plus saline or 1 mg/cm ropivacaine plus 25 micrograms, 50 micrograms, 75 micrograms, 100 micrograms or 150 micrograms clonidine for epidural analgesia. The sensory and motor function were determined at defined time intervals for 30 minutes. Heart rate and blood pressure were controlled and sedation score was judged. The postoperative 2-segment-regression of pin-prick and the onset of pain were recorded. RESULTS: The six groups were comparable in demographic data and in term of onset time. The prolongation of analgesia reached 513 +/- 92 min (p = 0.002) for 150 micrograms clonidine, 460 +/- 148 min (p = 0.073) for 100 micrograms clonidine, 440 +/- 86 min (p = 0.057) for 75 micrograms clonidine compared with 347 +/- 114 min for saline. In an equal manner, 2-segment-regression for pin-prick was extended to 251 +/- 47 min (p = 0.018) for 150 micrograms clonidine, 238 +/- 33 min (p = 0.034) for 100 micrograms clonidine, 229 +/- 29 min (p = 0.027) for 75 micrograms clonidine and 178 +/- 43 min for saline. Heart rate dropped down in all groups. Mean arterial pressure decreased significantly in the groups with 75, 100 and 150 micrograms clonidine. Sedation score increased continuously from 0.6 +/- 0.5 (saline) to 1.8 +/- 0.8 (150 micrograms clonidine). CONCLUSION: We conclude that 150 micrograms clonidine significantly enhances the duration of analgesia of epidurally administered ropivacaine in a mean of 171 mg. This time interval is longer than the one with 200 mg ropivacaine alone. But, there are side effects in form of decrease of arterial pressure. Cardiovascular monitoring seems to be essential. Because of the enhanced analgesia duration, the time interval for reloading epidural anaesthesia are increased.     

Relationship of immune response to heat-shock protein A and characteristics of Helicobacter pylori-infected patients

This study assessed the minimum dose of clonidine required to prolong the duration of both anesthesia and analgesia after axillary brachial plexus blockade. Eighty patients scheduled for elective hand surgery were divided into eight groups in a randomized, double-blind fashion. An axillary brachial plexus block was performed with 40 mL 1% mepivacaine plus 1:200,000 epinephrine. The control group received no clonidine. In the other groups, increasing doses of clonidine (0.1, 0.2, 0.3, 0.4, 0.5, 1, and 1.5 micrograms/kg) were added to the local anesthetic solution. Onset time, duration of anesthesia and analgesia, postoperative pain score, intake of analgesics, and adverse effects were recorded. The eight groups were comparable in terms of onset time, postoperative pain score, and analgesic requirement. The minimum dose of clonidine required to significantly prolong the duration of analgesia and anesthesia was, respectively, 0.1 and 0.5 microgram/kg. No side effects (sedation, drowsiness, bradycardia, arterial hypotension) were reported. We conclude that the dose of clonidine required to prolong significantly the duration of both anesthesia and analgesia after axillary brachial plexus blockade is 0.5 microgram/kg and that, at this dose, clonidine may be used without important reported side effects even in outpatients.     

The optimal test dose of epinephrine for epidural injection with lidocaine solution in awake patients premedicated with oral clonidine

We attempted to determine the optimal test dose of epinephrine for use with epidural anesthesia in awake patients premedicated with clonidine. Eighty-eight adult patients were randomized into two groups [oral premedication with clonidine 5 microg/kg (CLON) or no premedication (CONT)]. Before induction of general anesthesia, heart rate (HR) and blood pressure (BP) were measured for 3 min after the i.v. injection of 3 mL of 1.5% lidocaine containing epinephrine (0, 1.25, 2.5, 5, 7.5, or 15 microg) in a randomized, double-blind manner. We calculated 95% confidence intervals for the peak HR and BP increases induced by each dose of epinephrine. At 7.5 microg, epinephrine induced a significantly greater increase in HR and BP in CLON than in CONT. The 95% confidence interval for the HR change induced by 7.5 microg of epinephrine in CLON was nearly the same as the accepted standard dose of epinephrine (15 microg) in CONT. We conclude that premedication with clonidine enhances HR and BP responses to the i.v. administration of epinephrine-containing epidural test solutions. Consequently, 7.5 microg of epinephrine may be sufficient to enable detection of accidental injection into a blood vessel in awake patients premedicated with clonidine 5 microg/kg. Implications: Clonidine, a commonly used preanesthetic medication, alters patients' cardiovascular responses to drugs such as epinephrine. Our randomized, double-blind study suggests that, in awake patients receiving oral clonidine premedication, 7.5 microg of epinephrine (half the usual dose) is adequate as an indicator of accidental injection into the epidural vessels during epidural anesthesia.     

Determination of an effective dose of intrathecal morphine for pain relief after cesarean delivery

Very small doses of intrathecal (i.t.) morphine (25-200 microg) have been used in an effort to provide effective postoperative pain relief while minimizing side effects after cesarean delivery. We performed a double-blinded study in 40 patients presenting for elective cesarean delivery in which i.t. morphine was administered along with oral hydrocodone/acetaminophen and other medications commonly administered after cesarean delivery. We administered i.t. morphine by up-down sequential allocation of doses. For the purposes of this study, adequate postoperative analgesia was defined as comfort not requiring i.v. morphine for 12 h after spinal anesthesia with bupivacaine, fentanyl, and morphine. In addition, a time and cost comparison was performed for study patients receiving intrathecal morphine compared with a historical group of patients receiving patient-controlled analgesia with i.v. morphine. We were unable to determine with meaningful precision a dose of i.t. morphine to provide analgesia in this context. However, very small doses of i.t. morphine combined with oral hydrocodone/acetaminophen and other medications commonly prescribed after cesarean delivery provided postoperative pain relief with no more time commitment than patient-controlled analgesia (148 +/- 61 vs 150 +/- 57 min) and with significantly less acquisition cost ($15.13 +/- $4.40 vs $34.64 +/- $15.55). Implications: When used along with oral analgesics, very small doses of spinal morphine provide adequate pain relief after cesarean delivery. Spinal anesthetics, oral analgesics, and other medications commonly prescribed to treat side effects after cesarean delivery contribute significantly to this analgesia. When small doses of spinal morphine are used in this setting, they provide adequate analgesia and patient satisfaction that is time- and cost-effective.     

Is there any clinical advantage of increasing the pre-emptive dose of morphine or combining pre-incisional with postoperative morphine administration?

Pre-emptive treatment with an i.v. infusion of morphine 10 mg at induction reduces postoperative analgesic requirement and wound hypersensitivity compared with the same dose administered at the end of operation. Increasing the dose of preemptive morphine may potentially reduce postoperative pain further, while administering morphine at the end of operation, in addition to the beginning, may reduce pain generated by the sensory activity elicited from the wound in the immediate postoperative period. To examine this we have conducted a randomized, double-blind study in patients undergoing abdominal hysterectomy to compare the effect of morphine 20 mg administered before operation with 10 mg at induction and 10 mg on closure of the peritoneum. Postoperative pain was assessed by visual analogue score (VAS) at rest and on movement and by total morphine consumption administered by patient-controlled analgesia (PCA). Wound sensitivity was assessed by von Frey pain thresholds. Both groups had similar morphine consumption, VAS scores and touch and pain thresholds, and in both, secondary hyperalgesia was prevented. Nausea and vomiting scores were higher in the 20-mg group. There was no significant difference between the two groups and neither regimen appeared to offer obvious clinical advantages compared with a lower dose (10 mg) morphine analgesic strategy. Therefore, there may be a ceiling effect to the production of pre-emptive analgesia by morphine.     

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery. A randomised, double-blind, cross-over study with and without adrenaline

BACKGROUND: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. METHODS: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml.h-1 of bupivacaine 1 mg.ml-1, fentanyl 2 micrograms.ml-1, and adrenaline 2 micrograms.ml-1 were included. On the 1st and 2nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. RESULTS: The number of hypaesthetic dermatomal segments decreased (P < 0.001) and pain intensity at rest and when coughing increased (P < 0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15-20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng.ml-1 (P < 0.01), and there was more sedation during the period without adrenaline. CONCLUSIONS: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.