Transdermal nitroglycerine enhances spinal sufentanil postoperative analgesia following orthopedic surgery. (1/224)

BACKGROUND: Sufentanil is a potent but short-acting spinal analgesic used to manage perioperative pain. This study evaluated the influence of transdermal nitroglycerine on the analgesic action of spinal sufentanil in patients undergoing orthopedic surgery. METHODS: Fifty-six patients were randomized to one of four groups. Patients were premedicated with 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 2 ml of the test drug intrathecally (saline or 10 microg sufentanil). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control group received spinal saline and transdermal placebo. The sufentanil group received spinal sufentanil and transdermal placebo. The nitroglycerin group received spinal saline and transdermal nitroglycerine patch. Finally, the sufentanil-nitroglycerin group received spinal sufentanil and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale. RESULTS: The time to first rescue analgesic medication was longer for the sufentanil-nitroglycerin group (785+/-483 min) compared with the other groups (P<0.005). The time to first rescue analgesics was also longer for the sufentanil group compared with the control group (P<0.05). The sufentanil-nitroglycerin group group required less rescue analgesics in 24 h compared with the other groups (P<0.02) and had lesser 24-h pain visual analog scale scores compared with the control group (P<0.005), although these scores were similar to the sufentanil and nitroglycerin groups (P>0.05). The incidence of perioperative adverse effects was similar among groups (P>0.05). CONCLUSIONS: Transdermal nitroglycerine alone (5 mg/day), a nitric oxide generator, did not result in postoperative analgesia itself, but it prolonged the analgesic effect of spinal sufentanil (10 microg) and provided 13 h of effective postoperative analgesia after knee surgery.  (+info)

A double-blind comparison of 0.125% ropivacaine with sufentanil and 0.125% bupivacaine with sufentanil for epidural labor analgesia. (2/224)

BACKGROUND: This study intends to evaluate the benefits of the administration of intermittent bolus doses of ropivacaine (0.125%) compared with bupivacaine (0.125%) after addition of sufentanil for analgesia during labor. METHODS: One hundred thirty American Society of Anesthesiologists physical status 1 or 2 parturients were studied. The 90 initial patients were assigned randomly to receive 10 ml bupivacaine, 0.125%, plus 7.5 microg sufentanil (initial bupivacaine 0.125% group) or ropivacaine, 0.125%, plus 7.5 microg sufentanil (ropivacaine 0.125% group). Forty additional patients were recruited and received 0.125% bupivacaine plus 7.5 microg sufentanil (additional bupivacaine 0.125% group) or 0.100% bupivacaine plus 7.5 microg sufentanil (additional bupivacaine 0.100% group). The duration of analgesia, visual analogue scores for pain, motor blockade (using a six-point modified Bromage scale), patient satisfaction scores, nausea, pruritus, heart rate, and blood pressure were recorded. RESULTS: Bupivacaine 0.125% and ropivacaine 0.125% coadministered with sufentanil provided rapid and complete analgesia. Onset of analgesia occurred after +/-15 min and lasted +/-90 min. After the third epidural injection, patients in the ropivacaine group experienced significantly less severe motor blockade than patients in the initial bupivacaine 0.125% group. At this point, 93% of the patients in the ropivacaine group were free from motor impairment versus 66% in the bupivacaine group (P<0.05). Comparable levels of motor blockade were obtained in both additional groups. Patients' evaluation of their analgesia was worst in the bupivacaine 0.100% group. CONCLUSIONS: Ropivacaine 0.125% with sufentanil affords reliable analgesia with minimal motor blockade.  (+info)

Effects of propofol, propofol-nitrous oxide and midazolam on cortical somatosensory evoked potentials during sufentanil anaesthesia for major spinal surgery. (3/224)

Recording of cortical somatosensory evoked potentials (CSEP) enables monitoring of spinal cord function. We studied the effects of propofol, propofol-nitrous oxide or midazolam during sufentanil anaesthesia on CSEP monitoring during major spinal surgery. Thirty patients with normal preoperative CSEP were allocated randomly to one of the following anaesthesia regimens: propofol (2.5 mg kg-1 followed by 10-6 mg kg-1 h-1) with or without nitrous oxide, or midazolam (0.3 mg kg-1 followed by 0.15 mg kg-1 h-1) combined with sufentanil 0.5 microgram kg-1 h-1 in the propofol and midazolam groups, or 0.25 microgram kg-1 h-1 in the propofol-nitrous oxide group. CSEP were elicited by alternate right and left tibial posterior nerve stimulation and recorded before and after induction (15 min, 1, 2 and 3 h), and during skin closure. CSEP latencies were not significantly modified in the three groups. CSEP amplitude decreased significantly in the propofol-nitrous oxide group (from mean 2.0 (SEM 0.3) to 0.6 (0.1) microV; P < 0.05) but not in the propofol (from 1.8 (0.6) to 2.2 (0.3) microV) or midazolam (1.7 (0.5) to 1.6 (0.5) microV) groups. The time to the first postoperative voluntary motor response (recovery) delay was significantly greater in the midazolam group (115 (19) min) compared with the propofol and propofol-nitrous oxide groups (43 (8) and 41 (3) min, respectively). Consequently, the use of propofol without nitrous oxide can be recommended during spinal surgery when CSEP monitoring is required.  (+info)

Intrathecal neostigmine and sufentanil for early labor analgesia. (4/224)

BACKGROUND: Recent efforts to improve the combined spinal epidural (CSE) technique have focused on adding opioids to other classes of analgesics. In this study, the authors used intrathecal neostigmine in combination with intrathecal sufentanil to investigate the usefulness of neostigmine for reducing side effects and prolonging the duration of sufentanil. METHODS: One hundred six healthy pregnant women in labor were enrolled in this study, which was divided into four phases. In all phases, patients received a CSE anesthetic while in the lateral position. In phase I, three groups of six women each received intrathecal neostigmine, 5, 10, or 20 microg, in an open-label, dose-escalating safety assessment. In phase II, 24 women received intrathecal sufentanil alone to establish an ED50 (dose that produces > 60 min of labor analgesia in 50% of patients). In phase III, an ED50 was established for sufentanil combined with a fixed dose of neostigmine (10 microg). In phase IV, 40 women received either twice the ED50 of sufentanil alone or twice the ED50 of sufentanil plus neostigmine, 10 microg. RESULTS: Neostigmine alone had no adverse effects on maternal vital signs, fetal heart rate, or Apgar scores. Neostigmine, 20 microg, produced analgesia in one patient and severe nausea and vomiting in another. The ED50 for intrathecal sufentanil alone was 4.1 +/- 0.31 microg, and the ED50 for intrathecal sufentanil combined with neostigmine, 10 microg, was 3.0 +/- 0.28 microg. The duration of analgesia and side effects from double these ED50s (sufentanil, 9 microg, or sufentanil, 6 microg, plus neostigmine, 10 microg) were similar between groups. CONCLUSIONS: The 10-microg intrathecal neostigmine dose alone produced no analgesia or side effects, but reduced the ED50 of intrathecal sufentanil by approximately 25%. Additionally, doses approximately double these ED50s each produced a similar duration of analgesia and side effects, indicating intrathecal neostigmine shifts the dose-response curve for intrathecal sufentanil to the left.  (+info)

Alfentanil causes less postoperative nausea and vomiting than equipotent doses of fentanyl or sufentanil in outpatients. (5/224)

BACKGROUND: The relative potencies of alfentanil, fentanyl, and sufentanil as a risk factor for postoperative nausea and vomiting have not been determined. They were compared in a randomized study designed to obtain equipotent plasma concentrations of these three opioids at the beginning of the recovery period. METHODS: The study included 274 patients treated on an outpatient basis. The steady state opioid plasma concentration providing a predicted 50% reduction of the minimum alveolar concentration of isoflurane was used to determine the relative potency of the opioids. The opioids were prepared in equal volumes at concentrations of alfentanil 150 microg/ml, fentanyl 50 microg/ml, and sufentanil 5 microg/ml and were administered in vol/kg. Anesthesia was induced in a blinded fashion with a bolus of the study opioid (0.05 ml/kg) and 4-6 mg/kg thiopental and was maintained with isoflurane (0.6-1%) in a nitrous oxide-oxygen mixture with a continuous infusion of the study opioid (0.06 ml x kg(-1) x h(-1)). If necessary, up to five additional boluses of opioid (0.02 ml/kg) could be given. This opioid administration protocol was tested by pharmacokinetic simulations. RESULTS: The incidence of postoperative nausea and vomiting was not different in the postanesthesia care unit, but in the ambulatory surgery unit it was significantly lower for alfentanil compared with fentanyl and sufentanil (12, 34, and 35%, respectively P < 0.005). Pharmacokinetic modeling showed that the end-anesthesia opioid plasma concentrations were approximately equipotent in the three groups. However, modeling does not support that the difference between groups in the postoperative period can be explained by a more rapid disappearance of alfentanil from the plasma. CONCLUSIONS: Alfentanil, compared with approximately equipotent doses of fentanyl and sufentanil, is associated with a lower incidence of postoperative nausea and vomiting in outpatients.  (+info)

Comparative spinal distribution and clearance kinetics of intrathecally administered morphine, fentanyl, alfentanil, and sufentanil. (6/224)

BACKGROUND: Despite widespread use, little is known about the comparative pharmacokinetics of intrathecally administered opioids. The present study was designed to characterize the rate and extent of opioid distribution within cerebrospinal fluid, spinal cord, epidural space, and systemic circulation after intrathecal injection. METHODS: Equal doses of morphine and alfentanil, fentanyl, or sufentanil were administered intrathecally (L3) to anesthetized pigs. Microdialysis probes were used to sample cerebrospinal fluid at L2, T11, T7, T3, and the epidural space at L2 every 5-10 min for 4 h. At the end of the experiment, spinal cord and epidural fat tissue were sampled, and each probe's recovery was determined in vitro. Using SAAM II pharmacokinetic modeling software (SAAM Institute, University of Washington, Seattle, WA), the data were fit to a 16-compartment model that was divided into four spinal levels, each of which consisted of a caternary arrangement of four compartments representing the spinal cord, cerebrospinal fluid, epidural space, and epidural fat. RESULTS: Model simulations revealed that the integral exposure (area under the curve divided by dose) of the spinal cord (i.e., effect compartment) to the opioids was highest for morphine because of its low spinal cord distribution volume and slow clearance into plasma The integral exposure of the spinal cord to the other opioids was relatively low, but for different reasons: alfentanil has a high clearance from spinal cord into plasma, fentanyl distributes rapidly into the epidural space and fat, and sufentanil has a high spinal cord volume of distribution. CONCLUSIONS: The four opioids studied demonstrate markedly different pharmacokinetic behavior, which correlates well with their pharmacodynamic behavior.  (+info)

Involvement of the cyclic AMP system in the switch from tolerance into supersensitivity to the antinociceptive effect of the opioid sufentanil. (7/224)

1. We have previously demonstrated that chronic and simultaneous treatment of rats with the mu-opioid receptor agonist sufentanil and the Ca(2+) channel blocker nimodipine, not only prevented tolerance development, but the animals became supersensitive to the antinociceptive effect of the opioid. The focus of the present work was to determine the possible involvement of cross interactions between the adenylyl cyclase pathway and L-type voltage-sensitive Ca(2+)-channels, in modulating the switch from opioid tolerance into supersensitivity. 2. The modulatory effect of sufentanil on adenylyl cyclase activity was determined by measuring cyclic AMP production in slices from the cortex of rats rendered tolerant or supersensitive to the antinociceptive effect of the opioid. Tolerance was induced by chronic infusion of sufentanil, at a rate of 2 microg h(-1), for 7 days. Supersensitivity was induced by concurrent infusion of sufentanil (2 microg h(-1)) and nimodipine (1 microg h(-1)) for 7 days. Antinociception was evaluated by the tail-flick test. 3. Tolerance to the analgesic effect of sufentanil was associated with a significant reduction in the response of adenylyl cyclase to forskolin. Furthermore, the effect of the opioid on forskolin-induced cyclic AMP accumulation was abolished. On the other hand, supersensitivity to the analgesic effect of the opioid was associated with an increase in both, the adenylyl cyclase response to forskolin, and the opioid inhibition of cyclic AMP production. 4. We suggest that sustained L-type Ca(2+) channel blockade may result in changes in the adenylyl cyclase effector system triggered by mu-opioid receptor activation, leading to the switch from opioid tolerance into supersensitivity.  (+info)

The dose-response of intrathecal sufentanil added to bupivacaine for labor analgesia. (8/224)

BACKGROUND: Regional analgesia for labor often is initiated with an intrathecal injection of a local anesthetic and opioid. The purpose of this prospective, randomized, blinded study was to determine the optimal dose of intrathecal sufentanil when combined with 2.5 mg bupivacaine for labor analgesia. METHODS: One hundred seventy parous parturients with cervical dilation between 3-5 cm were randomized to receive intrathecal 0 (control), 2.5, 5.0, 7.5, or 10.0 microg sufentanil combined with 2.5 mg bupivacaine, followed by a lidocaine epidural test dose, for initiation of analgesia (34 patients in each group). Visual analog scores and the presence of nausea, vomiting, and pruritus were determined every 15 min until the patient requested additional analgesia. Fetal heart rate tracings were compared between groups. RESULTS: Groups were similar for age, height, weight, oxytocin dose, duration of labor, and baseline visual analog scores. Duration of action was significantly shorter for control patients (39 +/- 25 min [mean +/- SD]) compared with those administered sufentanil, all doses (93 +/- 32, 93 +/- 47, 94 +/- 33, 97 +/- 39 min), but was not different among groups administered 2.5, 5.0, 7.5, or 10.0 microg sufentanil. More patients who received 10 microg sufentanil reported nausea and vomiting than did control patients. The severity of pruritus increased with administration of 7.5 and 10.0 microg sufentanil. There was no difference in fetal heart rate changes among groups. CONCLUSIONS: Intrathecal bupivacaine (2.5 mg) without sufentanil did not provide satisfactory analgesia for parous patients. However, bupivacaine combined with 2.5 microg sufentanil provided analgesia comparable to higher doses, with a lower incidence of nausea and vomiting and less severe pruritus.  (+info)

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