Anesthesia and analgesia
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Anesthesia and analgesia · Dec 1997
Randomized Controlled Trial Comparative Study Clinical TrialContribution of the spinal cord to arousal from inhaled anesthesia: comparison of epidural and intravenous fentanyl on awakening concentration of isoflurane.
To investigate the contribution of modulation of afferent nociceptive inputs by an opioid in the spinal cord to arousal from inhaled anesthesia, we determined the awakening concentration of isoflurane in 50 unpremedicated patients scheduled for abdominal hysterectomy. Patients were assigned randomly to three groups. Group I received bolus injections of both epidural and intravenous (I.V.) saline, followed by both epidural and I.V. infusions at the rate of 0.2 mL x kg(-1) h(-1). Group II received an I.V. injection of fentanyl 2 microg/kg, followed by an infusion at the rate of 25 ng x kg(-1) x min(-1), and Group III received an epidural injection and infusion in the same administration regimen as Group II. Anesthesia was induced with and maintained by isoflurane in an air/oxygen mixture (fraction of inspired oxygen = 0.5) with no adjuvant drugs. The study drug was administered at the start of retroperitoneal suturing. The awakening concentrations of isoflurane in Groups I, II, and III (mean +/- SD) were 0.32% +/- 0.07%, 0.31% +/- 0.06%, and 0.24% +/- 0.06%, respectively. At that time, plasma fentanyl concentrations in Groups II and III were 1.12 +/- 0.09 ng/mL and 0.65 +/- 0.04 ng/mL, respectively. Epidural fentanyl infusion reduced the awakening concentration of isoflurane more (P < 0.01) than I.V. fentanyl infusion, despite the lower plasma concentration (P < 0.01) in the epidural group. These findings suggest that epidural fentanyl delays arousal from inhaled anesthesia by modulating the afferent nociceptive inputs in the spinal cord. The spinal cord may contribute to arousal from inhaled anesthesia through the regulation of afferent inputs by opioids along with the supraspinal region of the central nervous system (CNS), even if the effects of subarachnoid fentanyl on the higher CNS via the cephalad migration is taken into consideration. ⋯ The present study revealed that the spinal cord, the lower level of central nervous system, contributed to arousal from general anesthesia, along with the higher central nervous system, by comparing the concentrations of an inhaled anesthetic, isoflurane, in the expiration of patients receiving systemic or regional administration of an opioid, fentanyl.
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Anesthesia and analgesia · Dec 1997
Randomized Controlled Trial Clinical TrialLate-onset preemptive analgesia associated with preincisional large-dose alfentanil.
Few studies using systemic opioids have been adequately designed to demonstrate a preemptive effect. We investigated the preemptive effect of intraoperative large-dose intravenous (I.V.) opioids over a 72-h period after lower abdominal surgery. Thirty-eight ASA physical status I or II patients undergoing abdominal hysterectomy were studied in a prospective, randomized, double-blind design. Group PRE received alfentanil 70 microg/kg over 10 min before surgical incision; Group POST received alfentanil 70 microg/kg over 10 min after incision. Patients received no other intraoperative opioid. Pain was treated in the recovery room with 2-mg I.V. boluses of morphine and was subsequently managed via patient-controlled analgesia (PCA) using morphine sulfate. Visual analog scale pain scores at rest (VAS-R) and on movement (VAS-M) and PCA morphine consumption were recorded for 72 hours. VAS-M and VAS-R scores did not differ at any point, and morphine consumption was similar in both groups over the initial 48 h. Group PRE used significantly less morphine from 48 to 72 h postoperatively (P < 0.02). We conclude that presurgical incisional (i.e., compared with postincisional) large-dose opioid exposure results in a modest, late decrease in postoperative morphine consumption, with no clinical impact on early postoperative pain. Timing of the observed reduction coincides with maximal output of substances implicated in experimental hyperalgesia. ⋯ When given before surgical incision, alfentanil, a short-acting narcotic, was associated with a reduction in morphine requirements 48-72 h after surgery. Brief interventions may have a delayed and sustained impact on pain perception, possibly by reducing mechanisms of sensitization.
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Anesthesia and analgesia · Dec 1997
Randomized Controlled Trial Comparative Study Clinical TrialPostoperative analgesic requirement after cesarean section: a comparison of anesthetic induction with ketamine or thiopental.
In a randomized, double-blind study, we compared postoperative pain and analgesic requirement in patients who underwent elective cesarean section under general anesthesia induced with thiopental 4 mg/kg (n = 20) or ketamine 1 mg/kg (n = 20). Anesthesia was maintained with nitrous oxide and isoflurane. Postoperative analgesia was provided by patient-controlled analgesia (PCA) using morphine. Median (range) time to first PCA demand was greater in the ketamine group (28 [3-134] min) compared with the thiopental group (20.5 [3-60] min; P = 0.04). Median (range) morphine consumption over 24 h was less in the ketamine group (24.3 [3-41] mg) compared with the thiopental group (35 [4-67] mg; P = 0.017). Visual analog scale pain scores were similar between groups. No patients had recall of intraoperative events or unpleasant dreams. Two patients in the thiopental group and one patient in the ketamine group had pleasant intraoperative dreams. Apgar scores were similar between groups. Median umbilical venous pH was higher (7.33 vs 7.31; P = 0.04) and attributable to lower median umbilical venous Pco2 (5.72 vs 6.14 kPa; P = 0.02) in the ketamine group compared with the thiopental group. Induction of anesthesia for cesarean section using ketamine is associated with a lower postoperative analgesic requirement compared with thiopental. ⋯ Patients who had anesthesia for cesarean section induced with ketamine required less analgesic drugs in the first 24 h compared with patients who received thiopental. Ketamine, unlike thiopental, has analgesic properties that may reduce sensitization of pain pathways and extend into the postoperative period.
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Anesthesia and analgesia · Dec 1997
Randomized Controlled Trial Clinical TrialThe effects of epsilon-aminocaproic acid on fibrinolysis and thrombin generation during cardiac surgery.
Despite the efficacy of antifibrinolytic drugs in reducing bleeding after cardiac surgery, concerns remain regarding their potential to promote thrombosis. We examined the effect of the antifibrinolytic drug, epsilon-aminocaproic acid (EACA) on fibrinolysis and thrombin generation during cardiac surgery. Forty-one adults undergoing primary coronary artery bypass graft surgery requiring cardiopulmonary bypass (CPB) were prospectively randomized in a double-blind trial to receive either saline or EACA. A loading dose of 150 mg/kg EACA was given before anesthetic induction, followed by a 15 mg x kg(-1) x h(-1) infusion, which continued until 3 h after CPB. Plasma samples for the measurement of D-dimer, thrombin-antithrombin III, and soluble fibrin were obtained before surgery, 1 h on CPB, and 3 and 20 h after CPB. In the EACA group, fibrinolytic activity, as measured by D-dimer, was significantly decreased 3 h after CPB, (0.51 +/- 0.15 mg/L vs 1.13 +/- 0.14 mg/L, P < 0.005). Decreased fibrinolytic activity was accompanied by decreased bleeding in the EACA group (660 +/- 127 mL vs 931 +/- 113 mL, P < 0.05). No differences in the generation of thrombin or soluble fibrin were apparent between the two groups. Suppression of fibrinolytic activity in the absence of concomitant reductions in thrombin generation suggests that EACA could potentiate a hypercoagulable prethrombotic state in the perioperative setting. ⋯ In a randomized, prospective trial of primary cardiac surgery, we demonstrated that the synthetic antifibrinolytic drug epsilon-aminocaproic acid suppresses fibrinolysis with no effects on thrombin generation. These results suggest the potential for synthetic antifibrinolytic drugs to induce a hypercoagulable prethrombotic state in the perioperative setting.
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Anesthesia and analgesia · Dec 1997
Randomized Controlled Trial Comparative Study Clinical TrialPharmacokinetics and pharmacodynamics of propofol in a new solvent.
Pain on injection is the most commonly reported adverse event after propofol injection. In a randomized, cross-over study in two groups of 12 healthy male volunteers (24-42 yr), we compared the pharmacokinetics and pharmacodynamics of two new propofol formulations (1% and 2% concentrations) in a fat emulsion consisting of medium- and long-chain triglycerides with the standard propofol formulation. After a single intravenous bolus injection of 2 mg/kg, propofol blood levels were measured for 24 h and evaluated according to an open three-compartment model. The derived pharmacokinetic variables were not different among formulations. Additionally, electroencephalographic recordings of the onset and duration of hypnotic action were comparable with all formulations. After propofol 1% in the new formulation, fewer volunteers reported severe or moderate pain on injection (9%) than after the standard formulation (59%) (P < 0.05). We attribute this result to a lower concentration of free propofol in the aqueous phase of the new formulation. ⋯ Changing the composition of the carrier fat emulsion for propofol does not have an impact on the pharmacokinetics and efficacy of propofol, but it promises to provide better patient acceptance by lowering the incidence of moderate and severe pain on injection.