Anesthesia and analgesia
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Anesthesia and analgesia · Aug 2005
Review Meta AnalysisRevising a dogma: ketamine for patients with neurological injury?
We evaluated reports of randomized clinical trials in the perioperative and intensive care setting concerning ketamine's effects on the brain in patients with, or at risk for, neurological injury. We also reviewed other studies in humans on the drug's effects on the brain, and reports that examined ketamine in experimental brain injury. In the clinical setting, level II evidence indicates that ketamine does not increase intracranial pressure when used under conditions of controlled ventilation, coadministration of a gamma-aminobutyric acid (GABA) receptor agonist, and without nitrous oxide. Ketamine may thus safely be used in neurologically impaired patients. Compared with other anesthetics or sedatives, level II and III evidence indicates that hemodynamic stimulation induced by ketamine may improve cerebral perfusion; this could make the drug a preferred choice in sedative regimes after brain injury. In the laboratory, ketamine has neuroprotective, and S(+)-ketamine additional neuroregenerative effects, even when administered after onset of a cerebral insult. However, improved outcomes were only reported in studies with brief recovery observation intervals. In developing animals, and in certain brain areas of adult rats without cerebral injury, neurotoxic effects were noted after large-dose ketamine. These were prevented by coadministration of GABA receptor agonists. ⋯ Ketamine can be used safely in neurologically impaired patients under conditions of controlled ventilation, coadministration of a {gamma}-aminobutyric acid receptor agonist, and avoidance of nitrous oxide. Its beneficial circulatory effects and preclinical data demonstrating neuroprotection merit further animal and patient investigation.
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Anesthesia and analgesia · Aug 2005
The gamma-subunit governs the susceptibility of recombinant gamma-aminobutyric acid type A receptors to block by the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N).
To identify anesthetic effects that produce the different components of the complex anesthetic state, the so-called nonanesthetics/nonimmobilizer classes of compounds have been introduced. Because ionotropic gamma-aminobutyric acid type A (GABA(A)) receptors play an important role in the mediation of the central nervous system (CNS) effects of general anesthetics, and their susceptibility to modulation by various drugs depends on subunit composition, we have compared the effect of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6) on GABA(A) receptors expressed in human embryonic kidney 293 cells transfected with alpha1beta2 versus alpha1beta2gamma2s subunits. Using rapid perfusion and whole-cell recording techniques, we found that, like isoflurane, F6 blocked GABA-induced currents through alpha1beta2 receptors but, unlike isoflurane, the presence of the gamma2s subunit conferred complete resistance to block by F6. Also, in contrast to isoflurane, F6 had no effect on deactivation kinetics of GABA-induced currents in either type of receptor. We conclude that modulation of alphabetagamma receptors plays little or no role in the actions of F6, but the block of alphabeta receptors may contribute to its effects on the CNS. ⋯ Gamma-aminobutyric acidA receptors are the target of numerous drugs affecting the central nervous system. The subunit composition of the GABAA receptors governs their interaction with many drugs. We investigated whether the gamma-subunit influences the interaction with the nonimmobilizer F6.
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Anesthesia and analgesia · Aug 2005
Randomized Controlled Trial Comparative Study Clinical TrialA double-blind comparison of intravenous ondansetron and placebo for preventing postoperative emesis in 1- to 24-month-old pediatric patients after surgery under general anesthesia.
We assessed the efficacy and safety of ondansetron (0.1 mg/kg IV) prophylactically administered before surgery for prevention of postoperative vomiting (POV) in a double-blind, placebo-controlled study of 670 pediatric patients, 1- to 24-mo-old, undergoing elective surgery under general anesthesia. The study enrolled 335 children in each treatment group (ondansetron versus placebo). Significantly fewer children treated with ondansetron exhibited emesis or discontinued the study prematurely after surgery (ondansetron, 11%; placebo, 28%; odds ratio = 0.33; P < 0.0001). The number required to treat prophylactically with ondansetron to prevent POV was approximately six. Ondansetron treatment also resulted in fewer patients requiring rescue medication or assumed to have had rescue upon early discontinuation from the study during the postoperative period (ondansetron, 5%; placebo, 10%) and less emesis (0 of 6) after rescue medication when compared with placebo (7 of 21). The incidence of POV and other antiemetic effects of ondansetron were similar in children aged 1-12 mo and 13-24 mo and in children prospectively expected or not expected to require opioids as part of their anesthetic or analgesic management. Ondansetron was well tolerated; the incidence of adverse events considered possibly related to study drug was similar between treatment groups (ondansetron, 1.8%; placebo, 1.5%). ⋯ This prospective, randomized, double-blind, placebo-controlled study establishes the efficacy and tolerability of IV ondansetron (0.1 mg/kg) in the prevention of postoperative emesis in 1- to 24-mo-old pediatric patients undergoing elective surgery under general anesthesia.
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Anesthesia and analgesia · Aug 2005
Randomized Controlled Trial Comparative Study Clinical TrialThe short-lasting analgesia and long-term antihyperalgesic effect of intrathecal clonidine in patients undergoing colonic surgery.
In this study, we investigated the antihyperalgesic effect of clonidine after surgery. Sixty patients undergoing right colic resection were studied. Patients were randomized to receive prior to general anesthesia a 2-mL intrathecal (IT) injection of 300 microg of clonidine or saline, or 10 mg of bupivacaine. General anesthesia was achieved using a target concentration propofol infusion and monitored using bispectral index. Postoperative analgesia was provided by morphine IV given through a patient-controlled analgesia device. Postoperative analgesia was assessed by morphine requirements and visual analog scale pain scores at rest, cough, and movement during the first 72 h. Mechanical hyperalgesia was measured by von Frey filaments. Patients were questioned regarding residual pain at 2 wk,1, 6, and 12 mo. The patient-controlled analgesia morphine requirements were significantly smaller in the IT clonidine group (31.5 +/- 12 versus 91 +/- 25.5 and 43 +/- 15 mg, respectively, in groups clonidine, saline, and bupivacaine: P < 0.05 at 72 postoperative hours). The area of hyperalgesia at 72 h was 3 +/- 5 cm(2) in the clonidine group versus 90 +/- 30 and 35 +/- 20 cm(2) in the saline and bupivacaine groups (P < 0.05). At 6 mo, fewer patients in the clonidine group experienced residual pain than in the saline group (0 of 20 versus 6 of 20, P < 0.05). We conclude that both intraoperative spinal clonidine and bupivacaine improve immediate postoperative analgesia. IT clonidine was, however, more potent than IT bupivacaine to reduce postoperative secondary hyperalgesia. ⋯ Spinal clonidine contributes to the reduction of secondary hyperalgesia in patients recovering from abdominal surgery.