Opioid use after propofol or sevoflurane anesthesia: a randomized trial.

BACKGROUND: The intravenous anesthetic propofol is a gamma-aminobutyric acid A receptor agonist. Propofol promotes analgesia by depressing nociceptive transmission in peripheral neurons, antagonizing N-methyl-D-aspartate receptors, and activating gamma-aminobutyric acid A receptors in dorsal root ganglion receptor cells. Nevertheless, it remains unclear whether intraoperative propofol causes clinically meaningful postoperative analgesia. We therefore tested the hypothesis that patients anesthetized with sevoflurane require a greater quantity of postoperative opioids (from the end of surgery until the next postoperative morning) than those anesthetized with propofol. METHODS: With Institutional Review Board and EudraCT Number approval (2009-011038-82) and patients' informed consent, ninety patients scheduled for open vein stripping were randomized to either sevoflurane or propofol anesthesia at the Medical University of Vienna General Hospital and the Danube Hospital, the largest regional hospital in Vienna. Pain was treated with bolus piritramide and patient-controlled morphine hydrochloride. The primary outcome was total opioid use from the end of surgery until the first postoperative morning. For the initial four postoperative hours and on the first postoperative morning, a blinded investigator recorded pain scores on an 11-point Likert verbal response scale. RESULTS: The median [interquartile range] morphine sulfate equivalents were 9.8 [4-19] mg in the sevoflurane group and 10 [6-20] mg in the propofol group. Sevoflurane was not superior to propofol on postoperative opioid consumption, giving a ratio of means of 0.91 (95% interim-adjusted confidence interval [CI], 0.33 to 2.45; P = 0.74). Additionally, no difference in pain scores was found over time between the two groups, with a mean difference on an 11-point scale of 0.20 (95% interim-adjusted CI, -0.36 to 0.73; P = 0.31). CONCLUSION: Intraoperative sevoflurane did not reduce postoperative analgesia. This finding is consistent with the results in most previous reports. This trial was registered at ClinicalTrials.gov: NCT00712517.

Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients.

BACKGROUND: Previous studies show a prolongation of activated partial thromboplastin time and prothrombin time in healthy volunteers after treatment with sugammadex. The authors investigated the effect of sugammadex on postsurgical bleeding and coagulation variables. METHODS: This randomized, double-blind trial enrolled patients receiving thromboprophylaxis and undergoing hip or knee joint replacement or hip fracture surgery. Patients received sugammadex 4 mg/kg or usual care (neostigmine or spontaneous recovery) for reversal of rocuronium- or vecuronium-induced neuromuscular blockade. The Cochran-Mantel-Haenszel method, stratified by thromboprophylaxis and renal status, was used to estimate relative risk and 95% confidence interval (CI) of bleeding events with sugammadex versus usual care. Safety was further evaluated by prespecified endpoints and adverse event reporting. RESULTS: Of 1,198 patients randomized, 1,184 were treated (sugammadex n = 596, usual care n = 588). Bleeding events within 24 h (classified by an independent, blinded Adjudication Committee) were reported in 17 (2.9%) sugammadex and 24 (4.1%) usual care patients (relative risk [95% CI], 0.70 [0.38 to 1.29]). Compared with usual care, increases of 5.5% in activated partial thromboplastin time (P < 0.001) and 3.0% in prothrombin time (P < 0.001) from baseline with sugammadex occurred 10 min after administration and resolved within 60 min. There were no significant differences between sugammadex and usual care for other blood loss measures (transfusion, 24-h drain volume, drop in hemoglobin, and anemia), or risk of venous thromboembolism, and no cases of anaphylaxis. CONCLUSION: Sugammadex produced limited, transient (<1 h) increases in activated partial thromboplastin time and prothrombin time but was not associated with increased risk of bleeding versus usual care.

Intrapulmonary shunt after cardiopulmonary bypass: the use of vital capacity maneuvers versus off-pump coronary artery bypass grafting.

OBJECTIVES: It has been proved in human subjects and animals that atelectasis is a major cause of intrapulmonary shunting and hypoxemia after cardiopulmonary bypass. Animal studies suggest that shunting can be prevented entirely by a total vital capacity maneuver performed before termination of bypass. This study aimed to test this theory in human subjects and to evaluate possible advantages of off-pump coronary artery bypass grafting. METHODS: Twenty-four patients scheduled for coronary artery bypass grafting were randomly assigned to receive no total vital capacity maneuver (control group, n = 12) or standard total vital capacity maneuvers (TVCM group, n = 12). Additionally, 12 consecutive patients undergoing off-pump coronary artery bypass grafting (off-pump group) were studied. Systemic and central hemodynamics, the pattern of breathing, and ventilatory mechanics were evaluated after induction of anesthesia, after sternotomy, after cardiopulmonary bypass and skin closure, and 4 hours after extubation. RESULTS: The use of total vital capacity maneuvers reduced (P <.05) intrapulmonary shunting after termination of cardiopulmonary bypass. However, shunting increased (P <.05) in all groups (control group, 8.2% +/- 3.3% vs 25.6% +/- 8.1%; TVCM group, 8.7% +/- 3.4% vs 24.4% +/- 8.5%; and off-pump group, 7.8% +/- 2.8% vs 14.0% +/- 5.3%) after extubation, but the increase was significantly (P <.05) less pronounced in the off-pump group. Furthermore, pulmonary compliance decreased (P <.05) in all groups except the off-pump group after extubation. Duration of hospital and intensive care unit stay was significantly shorter (P <.05) in the off-pump group than in the other groups. CONCLUSION: The development of intrapulmonary shunting and hypoxemia after coronary artery bypass grafting can be substantially reduced by performance of total vital capacity maneuvers while patients are mechanically ventilated. However, off-pump coronary artery bypass surgery is superior in preventing shunting and hypoxemia after bypass grafting in the immediate and early postoperative periods, probably leading to substantially shorter intensive care unit and hospital stays.

The antinociceptive effect of intrathecal kynurenic acid and its interaction with endomorphin-1 in rats.

Kynurenic acid as an endogenous ligand antagonizes all types of ionotropic glutamate receptors, with preferential affinity for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor. The purpose of the present study was to investigate the antinociceptive potency of continuously administered kynurenic acid on carrageenan-induced thermal hyperalgesia by means of a paw withdrawal test in awake rats. The possible interaction between kynurenic acid and the endogenous mu-opioid receptor agonist peptide, endomorphin-1, was examined in the same set-up. Kynurenic acid at the higher doses (1-4 microg/min) significantly decreased the thermal hyperalgesia and increased the paw withdrawal latencies on the non-inflamed side. These doses were also associated with motor impairment on both sides. Low doses of kynurenic acid (0.01-0.1 microg/min) potentiated, but did not prolong, the antinociceptive effect of endomorphin-1 (0.1-1 microg/min) on the inflamed side. There was no sign of motor impairment during the combined treatment. These findings demonstrate that the combination of low doses of these two endogenous ligands provides effective and well-controlled antinociception without side effects.

Superior postoperative pain relief with thoracic epidural analgesia versus intravenous patient-controlled analgesia after minimally invasive pectus excavatum repair.

OBJECTIVE: Minimally invasive pectus excavatum repair is a common and painful surgical procedure in children and adolescents. Adequate postoperative pain therapy is important far beyond the immediate postoperative period because sensitization to painful stimuli can cause chronic pain or higher pain levels during subsequent surgical procedures. Although data in adults favor thoracic epidural anesthesia for pain control in thoracotomy, data for adolescents and children are scarce. We tested the hypothesis that pain relief with thoracic epidural analgesia was superior to that with intravenous patient-controlled analgesia after minimally invasive pectus excavatum repair in children and adolescents. METHODS: We performed a prospective randomized trial with adolescents who had undergone minimally invasive pectus excavatum repair to compare postoperative pain using two different postoperative pain therapy settings: intravenous patient-controlled analgesia (n = 20) with morphine versus continuous thoracic epidural analgesia (n = 20) with 0.2% ropivacain containing 2 microg/mL fentanyl. RESULTS: Forty patients (32 male and 8 female patients) aged 10 to 28 years were studied. The thoracic epidural analgesia group showed lower pain scores (P < .0001) and required less additional pain medication in conjunction with greater well-being postoperatively (P < .0001) compared with patients receiving patient-controlled intravenous morphine. There was no significant difference regarding the incidence of sedation (P = .38), nausea (P = .10), and pruritus (P = .72) in both groups. CONCLUSIONS: For adolescents undergoing minimally invasive pectus excavatum repair, thoracic epidural analgesia was superior to intravenous patient-controlled analgesia for postoperative analgesia, resulting in lower postoperative pain scores in conjunction with greater well-being.

Long-term changes in the antinociceptive potency of morphine or dexmedetomidine after a single treatment.

Acute tolerance develops after a single administration of opiate or alpha(2)-adrenergic agonists, but the characteristics of the delayed type of acute tolerance have not been analyzed in acute and inflammatory thermal pain tests. We investigated the long-term changes in the antinociceptive potency of morphine (10 mg/kg) injected intraperitoneally and the alpha(2)-adrenoceptor agonist dexmedetomidine (150 microg/kg intraperitoneally) on acute heat pain (tail-flick test) sensitivity and on carrageenan-induced inflammatory thermal hyperalgesia (paw withdrawal test) after a second injection 7 days later. The first treatment did not influence the baseline values on Day 8 in either test. In the tail-flick test, the antinociceptive potency of morphine, but not that of dexmedetomidine, was significantly decreased after repeated administration, suggesting a delayed type of acute tolerance to morphine. In contrast, the antihyperalgesic effect of morphine in the paw withdrawal test did not change after repeated injection, whereas the potency of dexmedetomidine was increased on Day 8. There were significant differences between the inflamed and noninflamed sides on Day 1 but not on Day 8, revealing an increased potency of the drugs on the inflamed side. There was no sign of cross-tolerance between the two drugs in either pain test. These data indicate long-term changes in the antinociceptive potency of morphine or dexmedetomidine after single treatment in different heat pain tests.

The significance of intrathecal catheter location in rats.

Although chronic intrathecal catheterization is a widely used method in rats, few calibration experiments have been performed. In this study, we investigated the correlation between the side position of the catheter tip and the side differences observed in the motor and sensory disturbances after intrathecal administration of lidocaine to a large number of rats. The existence of a sensory block was determined by the paw withdrawal test. The motor impairment was assessed by observing the complete clubbing of the hindpaw and measuring the hindpaw grip strength. After experimental use, we established the position of the catheter tip. The catheter tips were variously located in all directions of the transverse plane in the rat spinal subarachnoid space. Lidocaine administration (100 or 500 microg/5 microL; n = 264 and 112, respectively) led to dose-dependent motor and sensory disturbances. The effect of 100 microg of lidocaine exhibited side differences; i.e., the extents of both motor (r = 0.77) and sensory (r = 0.60 and r = 0.67 for the right and the left side, respectively) disturbances correlated significantly with the location of the catheter tip. Our data have shown that detection of the paralytic and/or antinociceptive effect of small-dose lidocaine before planned experiments is a simple and reliable method for prediction of the location of the catheter tip. We suggest that the position of the catheter might cause side differences in the drug effect, especially if small doses of drugs are administered and their effects are investigated on both sides.

Intrathecal clonidine for postoperative analgesia in elderly patients: the influence of baricity on hemodynamic and analgesic effects.

Intrathecal (IT) clonidine is an effective analgesic, but it also produces hemodynamic depression and sedation which are likely to be related to IT clonidine's cephalad spread within the cerebrospinal fluid. We hypothesized that IT clonidine's side effects could be reduced without compromising the duration and quality of analgesia by injecting clonidine IT in a hyperbaric solution and elevating the patient's trunk. We prospectively randomized 30 elderly patients to receive IT 150 microg of either isobaric (ISO) or hyperbaric (HYPER) clonidine for postoperative analgesia after surgical repair of traumatic hip fracture. Hemodynamics, IV fluid administration, visual analog pain scores, sedation scores, and clonidine cerebrospinal fluid levels were recorded at fixed intervals. Patients in the ISO group required significantly more crystalloid fluid administration (median, 2500 mL; range, 1500-3000 mL) than those in the HYPER group (median, 1500; range, 500-3000 mL) to maintain adequate arterial blood pressure (P < 0.01). Also, the decrease in heart rate was significantly more pronounced in the ISO than in the HYPER group (P < 0.01). The duration of analgesia was significantly larger in the ISO (median, 400 min; range, 115-400 min) than in the HYPER (median, 265 min; range, 205-400 min) group (P < 0.05). Sedation scores did not differ between groups. We conclude that increasing the baricity of IT clonidine solution in the conditions of our experiment reduces hemodynamic side effects but also analgesia from IT administered clonidine.

High-dose remifentanil does not impair cerebrovascular carbon dioxide reactivity in healthy male volunteers.

BACKGROUND: Cerebrovascular carbon dioxide reactivity during high-dose remifentanil infusion was investigated in volunteers by measurement of regional cerebral blood flow (rCBF) and mean CBF velocity (CBFv). METHODS: Ten healthy male volunteers with a laryngeal mask for artificial ventilation received remifentanil at an infusion rate of 2 and 4 microg x kg-1 x min-1 under normocapnia, hypocapnia, and hypercapnia. Stable xenon-enhanced computed tomography and transcranial Doppler ultrasonography of the left middle cerebral artery were used to assess rCBF and mean CBFv, respectively. If required, blood pressure was maintained within baseline values with intravenous phenylephrine to avoid confounding effects of altered hemodynamics. RESULTS: Hemodynamic parameters were maintained constant over time. Remifentanil infusion at 2 and 4 microg x kg-1 x min-1 significantly decreased rCBF and mean CBFv. Both rCBF and mean CBFv increased as the arterial carbon dioxide tension increased from hypocapnia to hypercapnia, indicating that cerebrovascular reactivity remained intact. The average slopes of rCBF reactivity were 0.56 +/- 0.27 and 0.49 +/- 0.28 ml. 100 g-1 x min-1 x mmHg-1 for 2 and 4 microg x kg-1 x min-1 remifentanil, respectively (relative change in percent/mmHg: 1.9 +/- 0.8 and 1.6 +/- 0.5, respectively). The average slopes for mean CBFv reactivity were 1.61 +/- 0.95 and 1.54 +/- 0.83 cm x s-1 x mmHg-1 for 2 and 4 microg x kg-1 x min-1 remifentanil, respectively (relative change in percent/mmHg: 1.86 +/- 0.59 and 1.79 +/- 0.59, respectively). Preanesthesia and postanesthesia values of rCBF and mean CBFv did not differ. CONCLUSION: High-dose remifentanil decreases rCBF and mean CBFv without impairing cerebrovascular carbon dioxide reactivity. This, together with its known short duration of action, makes remifentanil a useful agent in the intensive care unit when sedation that can be titrated rapidly is required.