Anesthesia and analgesia
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Anesthesia and analgesia · May 2001
The effects of FK506 on neurologic and histopathologic outcome after transient spinal cord ischemia induced by aortic cross-clamping in rats.
Spinal cord injury is a devastating complication of thoracoabdominal aortic surgery. We investigated the effect of the immunosuppressant FK506, a macrolide antibiotic demonstrated to have neuroprotective effects in cerebral ischemia models, in a rat model of transient spinal cord ischemia. Spinal cord ischemia was induced in anesthetized rats by using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy. Experimental groups were as follows: sham-operation; control, receiving only vehicle; FK506 A, receiving FK506 (1 mg/kg IV) before clamping; and FK506 B, receiving FK506 (1 mg/kg IV) at the onset of reperfusion. Neurologic status was assessed at 24 h and then daily up to 96 h with a 0 to 6 scale (0, normal function; 6, severe paraplegia). Rats were randomly killed at 24, 48, or 96 h, and spinal cords were harvested for histopathology. Physiologic variables did not differ significantly among experimental groups. All control rats suffered severe and definitive paraplegia. FK506-treated rats had significantly better neurologic outcome compared with control. Histopathologic analysis disclosed severe injury in the lumbar gray matter of all control rats, whereas most FK506-treated rats had less injury. These data suggest that FK506 can improve neurologic recovery and attenuate spinal cord injury induced by transient thoracic aortic cross-clamping. ⋯ A single dose-injection of the immunosuppressant FK506 significantly improved neurologic outcome and attenuated spinal cord injury induced by transient thoracic aortic cross-clamping in the rat.
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Anesthesia and analgesia · May 2001
Modulation of NMDA receptor function by ketamine and magnesium. Part II: interactions with volatile anesthetics.
Mg2+ and ketamine interact superadditively at N- methyl-D-aspartate (NMDA) receptors, which may explain the clinical efficacy of the combination. Because patients are usually exposed concomitantly to volatile anesthetics, we tested the hypothesis that volatile anesthetics interact with ketamine and/or Mg2+ at recombinantly expressed NMDA receptors. NR1/NR2A or NR1/NR2B receptors were expressed in Xenopus oocytes. We determined the effects of isoflurane, sevoflurane, and desflurane on NMDA receptor signaling, alone and in combination with S(+)-ketamine (4.1 microM on NR1/NR2A, 3.0 microM on NR2/NR2B) and/or Mg2+ (416 microM on NR1/NR2A, 629 microM on NR1/NR2B). Volatile anesthetics inhibited NR1/NR2A and NR1/NR2B glutamate receptor function in a reversible, concentration-dependent, voltage-insensitive and noncompetitive manner (half-maximal inhibitory concentration at NR1/NR2A receptors: 1.30 +/- 0.02 minimum alveolar anesthetic concentration [MAC] for isoflurane, 1.18 +/- 0.03 MAC for desflurane, 1.24 +/- 0.06 MAC for sevoflurane; at NR1/NR2B receptors: 1.33 +/- 0.12 MAC for isoflurane, 1.22 +/- 0.08 MAC for desflurane, and 1.28 +/- 0.08 MAC for sevoflurane). On both NR1/NR2A and NR1/NR2B receptors, 50% inhibitory concentration for volatile anesthetics was reduced approximately 20% by Mg2+, approximately 30% by S(+)-ketamine, and approximately 50% by the compounds in combination. Volatile anesthetic effects on NMDA receptors can be potentiated significantly by Mg2+, S(+)-ketamine, or-most profoundly-both. Therefore, the analgesic effects of ketamine and Mg2+, are likely to be enhanced in the presence of volatile anesthetics. ⋯ Clinically relevant concentrations of volatile anesthetics inhibit functioning of N-methyl-D-aspartate receptors expressed recombinantly in Xenopus oocytes. This inhibition is reversible, concentration-dependent and voltage-insensitive, and results from noncompetitive antagonism of glutamate/glycine signaling. In addition, these effects can be potentiated significantly by co-application of either Mg2+, S(+)-ketamine, or--most profoundly--both.
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Anesthesia and analgesia · May 2001
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialA randomized double-blinded multicenter comparison of remifentanil versus fentanyl when combined with isoflurane/propofol for early extubation in coronary artery bypass graft surgery.
We compared a fentanyl/isoflurane/propofol regimen with a remifentanil/isoflurane/propofol regimen for fast-track cardiac anesthesia in a prospective, randomized, double-blinded study on patients undergoing elective coronary artery bypass graft surgery. Anesthesia was induced with a 1-min infusion of 0.5 mg/kg propofol followed by 10-mg boluses of propofol every 30 s until loss of consciousness. After 0.2 mg/kg cisatracurium, a blinded continuous infusion of remifentanil at 1 microg. kg(-1). min(-1) or the equivalent volume rate of normal saline was then started. In addition, a blinded bolus syringe of 1 microg/kg remifentanil or 10 microg/kg fentanyl, respectively, was given over 3 min. Blinded remifentanil, 1 microg. kg(-1). min(-1) (or the equivalent volume rate of normal saline), together with 0.5% isoflurane, were used to maintain anesthesia. Significantly more patients (P < 0.01) in the fentanyl regimen experienced hypertension during skin incision and maximum sternal spread compared with patients in the remifentanil regimen. There were no differences between the groups in time until extubation, discharge from the surgical intensive care unit, ST segment and other electrocardiogram changes, catecholamine levels, or cardiac enzymes. The remifentanil-based anesthetic (consisting of a bolus followed by a continuous infusion) resulted in significantly less response to surgical stimulation and less need for anesthetic interventions compared with the fentanyl regimen (consisting of an initial bolus, and followed by subsequent boluses only to treat hemodynamic responses) with both drug regimens allowing early extubation. ⋯ Both fentanyl and the newer opioid remifentanil, when each is combined with isoflurane and propofol, allowed for fast-track cardiac anesthesia. The remifentanil regimen used in this study resulted in significantly less hemodynamic response to surgical stimulation.
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Anesthesia and analgesia · May 2001
Randomized Controlled Trial Multicenter Study Clinical TrialProlonged epidural infusions of ropivacaine (2 mg/mL) after colonic surgery: the impact of adding fentanyl.
We evaluated the safety and efficacy of a 72-h epidural infusion of ropivacaine and measured the impact of adding fentanyl 2 microg/mL to the required infusion rate, on the quality of postoperative pain relief and the incidence of side effects, after colonic surgery. One hundred fifty-five patients scheduled for elective colonic surgery were randomized in this trial. Epidural infusions of ropivacaine 2 mg/mL with fentanyl 2 microg/mL (R + F) and without fentanyl (R) were commenced during surgery and continued for 72 h postoperatively. This was a prospective, randomized, double-blinded, multi-center trial. The median infusion rate required was less in the R + F group (9.3 vs 11.5 mL/h, P < 0.001). Median pain scores at rest and on coughing were lower in the R + F group (P < 0.0001). The incidence of hypotension was more in the R + F group (P = 0.01). Time to readiness for discharge was delayed in the R + F group (median 6.6 vs 5.5 days, P = 0.012). The addition of fentanyl to ropivacaine resulted in decreased infusion rates and enhanced pain control; however, adverse effects were increased and readiness to discharge was delayed. ⋯ Epidural infusions of ropivacaine with and without fentanyl were administered to patients to control pain after colonic surgery. Patients who received ropivacaine with fentanyl had better pain control, increased side effects, and delayed readiness to discharge. This study questions the value of adding opioids to epidural infusions of local anesthetics.