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The transmission of viral disease in the operating room is an evolving problem. Advances in transfusion medicine have made blood supply safer than ever, whereas changes in transfusion practice have minimized the amount of blood transfused. The epidemiology of viral infection is changing in both the general population and among healthcare workers. Vaccination and prevention hold the key to future risk reduction for patients and providers.

Both dizocilpine (MK-801) and isoflurane antagonize glutamatergic neurotransmission. In this study, we examined the relative neuroprotective effects of these drugs administered in equianesthetic doses before the onset of focal cerebral ischemia. Rats were anesthetized with 1.0%-1.5% isoflurane and surgically prepared for filament occlusion of the middle cerebral artery (MCAO). After preparation, one group (n = 22) remained anesthetized with 0.7% isoflurane. Another group (n = 18) was given dizocilpine (1 mg/kg intraperitoneally), and isoflurane was discontinued. The third group (n = 18) was allowed to awaken immediately after the onset of ischemia. MCAO persisted for 75 min. Epidural temperature was controlled at 37.5[degree sign]C during ischemia and the first 22 h of recovery. A 7-day recovery interval was allowed. Total infarction volumes (mean +/- SD) were less for the dizocilpine group (100 +/- 65 mm3) versus the awake group (182 +/- 36 mm3; P = 0.001). Infarction volumes did not differ significantly between the isoflurane group (142 +/- 81 mm3) and either the dizocilpine (P = 0.11) or the awake group (P = 0.15). Isoflurane was examined at doses used clinically but smaller than those found to reduce N-methyl-D-aspartate (NMDA)-mediated injury in vitro. This study supports the hypothesis that NMDA receptor activation is injurious during focal ischemia and that amelioration of focal ischemic brain damage by NMDA receptor antagonists persists under normothermic conditions. Implications: Rats underwent focal cerebral ischemia with rigid maintenance of brain normothermia. The glutamate receptor antagonist dizocilpine was effective in reducing cerebral infarction size during persistent conditions of brain normothermia. In contrast, isoflurane administered at equianesthetic doses did not reduce infarction size. This study supports the hypothesis that N-methyl-D-aspartate receptor activation is injurious during focal ischemia and that amelioration of focal ischemic brain damage by N-methyl-D-aspartate receptor antagonists persists under normothermic conditions. (Anesth Analg 1998;87:72-8)

There is increasing evidence that pharmacologic antagonism of glutamatergic neurotransmission can potentiate the anesthetic effects of drugs such as halothane. The purpose of this study was to examine the anesthetic interaction between glutamate receptor antagonists. A competitive NMDA receptor antagonist (CGS 19755) and an AMPA receptor antagonist (NBQX) were administered either alone or in combination prior to determination of the minimum alveolar concentration (MAC) for halothane in the rat. CGS 19755 caused a dose-dependent maximum reduction in halothane MAC of approximately 80%. Doses of NBQX, which were low enough to cause no change in MAC when administered alone, substantially reduced MAC when administered with subanesthetic doses of CGS 19755. This effect decreased as the dose of CGS 19755 was increased. Finally, halothane MAC was reduced to zero when NBQX, in a dose sufficient to reduce halothane MAC by approximately 35% if given alone, was added to a pharmacodynamically similar dose of CGS 19755. Although MAC is believed to predominantly reflect nocioception at the spinal cord level, the results suggests that pharmacologic blockade of glutamatergic neurotransmission is sufficient to result in deep levels of anesthesia. Further, the effect of combinations of NMDA and AMPA receptor antagonists on halothane MAC is consistent with an in vivo physiologic interaction between the NMDA and AMPA receptors.

Background Glycine and glutamate binding sites are allosterically coupled at the N-methyl-D-aspartate (NMDA) receptor complex. Previous studies have shown that antagonism of glutamate at the NMDA receptor reduces the minimum alveolar concentration (MAC) for volatile anesthetics. 5-Nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA-1021) is a competitive antagonist at the glycine recognition site of the NMDA receptor. The purpose of this study was to determine whether glycine receptor antagonism also reduces volatile anesthetic requirements in the rat. Methods In experiment 1, Sprague-Dawley rats were anesthetized with halothane in 50% O2-balance N2 and their lungs mechanically ventilated. They were randomly assigned to one of three groups according to the dose of ACEA-1021 administered (0, 20, or 40 mg/kg intravenously; n = 6). The bolus dose of ACEA-1021 was followed by a continuous intravenous infusion of vehicle or ACEA-1021 at 14 mg.kg-1.h-1. Halothane MAC was then determined by the tail-clamp method. In experiment 2, awake rats were randomly assigned to groups according to the same dosages of ACEA-1021 as in experiment 1. Arterial CO2 tension and mean arterial pressure were recorded before and 5 and 30 min after the start of the infusion. The infusion was then stopped, and the time to recovery of the righting reflex was recorded. Results In experiment 1, ACEA-1021 decreased halothane MAC (mean +/- SD) in a dose-dependent manner (control, 0.95 +/- 0.15 vol%; ACEA-1021 20 mg/kg, 0.50 +/- 0.14 vol%; ACEA-1021 40 mg/kg, 0.14 +/- 0.16 vol%; P < 0.01). In experiment 2, arterial CO2 tension was increased by ACEA-1021 (control, 38 +/- 3 mmHg; ACEA-1021 20 mg/kg, 43 +/- 3 mmHg; ACEA-1021 40 mg/kg, 48 +/- 2 mmHg; P < 0.01). Mean arterial pressure was not affected by any dose of ACEA-1021. The righting reflex was abolished in rats receiving ACEA-1021 40 mg/kg only and recovered 30 +/- 7 min after discontinuation of the infusion. Conclusions Halothane MAC reduction by glycine receptor antagonism was greater than that previously observed for antagonism of glutamate at the NMDA or AMPA receptor. In rats receiving ACEA-1021 only, minimal hemodynamic depression and moderate hypoventilation were observed. Antagonism of glycine at the NMDA receptor recognition site offers a potential mechanism of action of anesthesia.

BACKGROUND Because glutamate antagonists can substantially alter the minimum alveolar concentration (MAC) of volatile anesthetics, glutamate has been implicated as an important neurotransmitter in processes contributing to the anesthetic state. Cerebral ischemia profoundly alters glutamatergic neurotransmission and thus may also alter halothane MAC. METHODS Fasted rats were surgically prepared for forebrain ischemia. One half of the animals served as operative shams (n = 24). Remaining rats underwent 10 min of bilateral carotid occlusion combined with systemic hypotension (n = 24). In animals in both groups brain circulation was restored for 1 h, 24 h, or 7 days (n = 8). At each of these intervals, MAC for halothane was determined by the tail-clamp method. Histologic damage in the hippocampus, cortex, caudoputamen, and thalamus was measured in animals allowed to survive 7 days. RESULTS Blood pressure, arterial blood gas tensions and pH, pericranial temperature, and plasma glucose values measured immediately before ischemia were similar among groups. Neither ischemia nor duration of reperfusion significantly altered halothane MAC as compared with operative shams (sham 1 h = 0.9 +/- 0.1 vol%, 24 h = 1.0 +/- 0.1 vol%, 7 days = 1.0 +/- 0.2 vol%; ischemia 1 h = 0.9 +/- 0.1 vol%, 24 h = 0.9 +/- 0.1 vol%, 7 days = 1.0 +/- 0.2 vol%). Histologic damage in the hippocampus and caudoputamen was severe in the ischemic group of animals. Mild injury was observed in the motor and cingulate cortex as well as the thalamus. There was no evidence of histologic injury in sham-operated animals. CONCLUSIONS The absence of effect of ischemic forebrain injury on halothane MAC is consistent with findings made in other models of supratentorial cerebral injury. These results support the contention that anatomic foci for motor responses elicited during MAC determination are localized at levels caudal to the forebrain.

BackgroundThere has been little systematic examination concerning the comparative effects of the anesthetized versus the awake state on outcome from cerebral ischemia. This experiment evaluated infart volume and neurologic function in rats subjected to temporary focal ishemia while anesthetized with

Forty ASA physical status I or II patients scheduled for elective Caesarean delivery were studied to determine the effect of epidural fentanyl on post-Caesarean delivery analgesic requirements as administered by intravenous patient-controlled analgesia (PCA). Following delivery of the infant, under epidural anaesthesia with lidocaine 2% with 1/200,000 epinephrine, patients were randomly assigned to receive either 10 ml of preservative-free normal saline via the epidural catheter or 100 micrograms of fentanyl with 8 ml preservative-free normal saline in a double-blinded fashion. On arrival in the post-anesthesia recovery room (PAR), patients were provided with intravenous PCA meperidine 12.5 mg every eight minutes as needed. Patients were visited at intervals over the next 24 hr to determine if any differences in narcotic requirements, demands for narcotics, or severity of pain were noted. No differences were observed in any values between the groups. It is concluded that a single bolus of epidural fentanyl does not provide an advantage for postoperative pain relief in this patient population.

Lidocaine and MgSO4 are often coadministered to patients with pregnancy-induced hypertension. This study examined whether MgSO4 alters the lidocaine-seizure threshold in the rat and, if so, whether systemic MgSO4 administration is as effective as intracerebroventricular MgSO4 infusion. In Experiment 1, rats were administered 50% MgSO4 or 0.9% NaCl intravenously (IV) (20 microL/h) for 5 days. In Experiment 2, rats were administered 0.9% NaCl, 0.8% MgSO4, or 2.0% MgSO4 (10 microL/h) via intracerebroventricular infusion for 24 h. All rats then underwent continuous IV lidocaine infusion until onset of electroencephalographic seizures. In Experiment 1, plasma [Mg2+] was greater in the MgSO4 group (5.1 +/- 1.5 mg/dL vs 1.8 +/- 0.3 mg/dL) but neither the dose of lidocaine required to induce seizures (MgSO4 = 19 +/- 2 mg/kg; saline = 23 +/- 5 mg/kg) nor brain [Mg2+] (MgSO4 = 794 +/- 17 micrograms/g; saline = 788 +/- 33 micrograms/g) were changed. In Experiment 2, intracerebroventricular MgSO4 increased both brain [Mg2+] (2% MgSO4 = 923 +/- 79 micrograms/g; saline = 788 +/- 35 micrograms/g) and the lidocaine seizure dose (2% MgSO4 = 39 +/- 7 mg/kg; saline = 26 +/- 3 mg/kg). Although intracerebroventricular administration of MgSO4 produces an anticonvulsant effect, chronic hypermagnesemia does not alter whole brain [Mg2+] and therefore offers no protection from lidocaine-induced seizures in this model.

We tested the hypothesis that glutamate receptor antagonists increase the dose of lidocaine required to induce seizure activity. Sprague-Dawley rats were anesthetized with halothane in 40% O2/balance N2 and mechanically ventilated. After surgical preparation, halothane was discontinued. Normocapnia, normoxia, and normothermia were maintained. The electroencephalogram (EEG) and arterial blood pressure were monitored continuously. Rats were then randomized to one of six groups (control, one of three intravenous [i.v.] bolus doses of the competitive glutamate N-methyl-D-aspartate [NMDA] receptor antagonist CGS 19755, or one of two i.v. bolus and continuous infusion regimens of the competitive glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA] receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)quinoxalline [NBQX]). Thirty minutes after onset of CGS 19755 or NBQX administration (end-tidal halothane0.2%), rats received a continuous i.v. infusion of 1.5% lidocaine until EEG seizures occurred. The duration of the infusion (min) and total lidocaine dose (mg/kg) administered were recorded. CGS 19755 increased the lidocaine seizure threshold in a log-linear dose-dependent fashion (P10(-6)). The largest dose of CGS 19755 (112.5 mg/kg) increased the time to initial EEG seizure activity more than twofold (e.g., control = 12.6 +/- 2.6 min; CGS 19755 = 28.6 +/- 6.9 min). The effect of AMPA receptor antagonism was less obvious because treatment resulted in an EEG morphology dissimilar to that observed in the CGS 19755 or control groups. Our findings indicate that competitive NMDA receptor antagonists (e.g., CGS 19755) increase the dose of lidocaine required for seizures.(ABSTRACT TRUNCATED AT 250 WORDS)

Various subtypes of receptors have been identified for glutamate, an excitatory neurotransmitter. Previous studies have shown that antagonism of glutamate at the NMDA receptors reduces minimum alveolar concentration (MAC) for volatile anesthetics. NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline) is a selective antagonist at the glutamatergic AMPA receptor. The purpose of this experiment was to determine whether AMPA receptor antagonism influences halothane MAC in the rat. Sprague-Dawley rats were anesthetized with halothane in 50% O2/balance N2, tracheally intubated and the lungs were mechanically ventilated. Increasing doses of NBQX were intravenously infused in three groups while the control group was infused with vehicle (D5W). Halothane MAC was then determined by the tail-clamp method. Halothane MAC was log-linearly related to plasma NBQX concentrations (MAC = 0.125 (In plasma concentration NBQX) + 1.035, r2 = 0.77). A maximal 58% reduction of halothane MAC was achieved with an NBQX loading dose of 42 mg/kg followed by a continuous infusion rate of 36 mg x kg-1 x h-1 (control = 1.02 +/- 0.07%; NBQX = 0.43 +/- 0.12%; P.01). Larger doses of NBQX were not possible because of the poor aqueous solubility of this compound. In a separate experiment, awake rats were randomly assigned to groups based on the dose of NBQX infused. Pa(CO2) and mean arterial pressure were measured at time 0 and at 5 and 30 min after start of NBQX infusion. The infusion was then stopped. Time until recovery of the righting reflex was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Some studies suggest that epidural analgesia prolongs labor and increases the incidence of cesarean section, especially if it is administered before 5 cm cervical dilation. The purpose of the current study was to determine whether early administration of epidural analgesia affects obstetric outcome in nulliparous women who are in spontaneous labor. Methods Informed consent was obtained from 344 healthy nulliparous women with a singleton fetus in a vertex presentation, who requested epidural analgesia during spontaneous labor at at least 36 weeks' gestation. Each patient was randomized to receive either early or late epidural analgesia. Randomization occurred only after the following conditions were met: (1) the patient requested pain relief at that moment, (2) a lumbar epidural catheter had been placed, and (3) the cervix was at least 3 cm but less than 5 cm dilated. Patients in the early group immediately received epidural bupivacaine analgesia. Patients in the late group received 10 mg nalbuphine intravenously. Late-group patients did not receive epidural analgesia until they achieved a cervical dilation of at least 5 cm or until at least 1 h had elapsed after a second dose of nalbuphine. Ten of the 344 patients were excluded because of a protocol violation or voluntary withdrawal from the study. Results Early administration of epidural analgesia did not increase the incidence of oxytocin augmentation, prolong the interval between randomization and the diagnosis of complete cervical dilation, or increase the incidence of malposition of the vertex at delivery. Also, early administration of epidural analgesia did not result in an increased incidence of cesarean section or instrumental vaginal delivery. Seventeen (10%) of 172 women in the early group and 13 (8%) of 162 women in the late group underwent cesarean section (relative risk for the early group 1.22; 95% confidence interval 0.62-2.40). Patients in the early group had lower pain scores between 30 and 150 min after randomization. Infants in the late group had lower umbilical arterial and venous blood pH and higher umbilical venous blood carbon dioxide tension measurements at delivery. Conclusions Early administration of epidural analgesia did not prolong labor, increase the incidence of oxytocin augmentation, or increase the incidence of operative delivery, when compared with intravenous nalbuphine followed by late administration of epidural analgesia, in nulliparous women who were in spontaneous labor at term.