Search

We previously showed that preischemic administration of high-dose isoflurane worsened the outcome from severe forebrain ischemia in rats. Conversely, high doses of sevoflurane have been reported to improve the outcome from forebrain ischemia when the insult is moderate. To clarify the dose-dependent effects of sevoflurane on severe forebrain ischemia, we performed an outcome study using an identical protocol to that in our previous study with isoflurane. Fasting male Sprague-Dawley rats underwent surgical preparation for forebrain ischemia under halothane anesthesia. Anesthesia was changed to fentanyl/nitrous oxide to eliminate the halothane, after which 30 minutes of 0.5, 1.0, 1.5, 2.0, or 2.5 minimum alveolar concentration sevoflurane was administered. Ten minutes of ischemia was induced by bilateral carotid occlusion plus systemic hypotension, in which cessation of electroencephalographic activity was confirmed. Sevoflurane was discontinued and anesthesia continued with fentanyl/nitrous oxide for an additional 100 minutes. Outcome evaluation at 5 days postischemia included seizure incidence, mortality rate, neuromotor score, and histologic injuries to the cerebral cortex and hippocampal CA1 and CA3. Different doses of sevoflurane did not statistically affect seizure incidence (10.0% to 18.2%), mortality rate (20.0% to 46.7%), cortical damage (mild to moderate degree), or hippocampal CA1 damage (93.7% to 96.7% neuronal necrosis) or CA3 damage (36.3% to 41.7%). Dose-dependent effects of sevoflurane were not observed for any of the outcome variables assessed in this rat model of severe forebrain ischemia.

Studies comparing the recovery profiles of isoflurane- and propofol-based anesthesia for major intracranial surgery have reported contradictory results. The aim of our study was to clarify the emergence status in both regimens by investigating uniformly managed neuroanesthesia cases. The anesthesia database at Yamagata University Hospital covering the period 2002–2005 was retrospectively investigated for adult patients who underwent craniotomy for primary brain tumor excision. General anesthesia was provided by an isoflurane- (ISO group) or propofol-based (PROP group) regimen. Times to extubation and operating room (OR) discharge, perioperative consciousness levels, and perioperative variables were compared. Of the 202 surgeries performed during the study period, 77 and 82 patients were anesthetized with isoflurane and propofol, respectively. Demographic data were comparable between the two groups, although the American Society of Anesthesiology grade was worse in the PROP group. Extubation times [39.5 ± 14.6 min (ISO) vs. 29.5 ± 14.9 min (PROP); P

Prostaglandin E(1) (PGE(1)) has been shown to provide short-term neuroprotection against various types of brain ischemia in a dose-dependent manner in mice. However, these findings were obtained from experiments performed without any control over physiological parameters. We performed an outcome study where physiological parameters were controlled in an attempt to confirm the dose-dependant neuroprotective effects of PGE(1).A rat model of severe forebrain ischemia was used. Two doses of PGE(1) were administered during the pre-ischemic period, a low dose (LowPG group) and a high dose (HighPG group). Normotension was maintained in the LowPG group, while hypotension was induced in the HighPG group. In separate groups, normal saline (Control) or sodium nitroprusside (SNP) were infused to compare outcomes under similar blood pressure conditions. Histological outcomes in the hippocampal CA1 and entorhinal cortex were evaluated 5 days post-ischemia.HighPG resulted in hyperglycemia. The percentage of dead neurons in the hippocampal CA1 and entorhinal cortex were similar in the Control, SNP, and HighPG groups, the percentage being significantly attenuated in the LowPG group (CA1: Control = 92.8 +/- 2.4%, LowPG = 85.0 +/- 8.5%, HighPG = 95.3 +/- 2.4%, and SNP = 96.4 +/- 0.7%, P0.01; entorhinal cortex: Control = 73.8 +/- 4.0%, LowPG = 53.2 +/- 12.3%, HighPG = 72.1 +/- 12.6%, and SNP = 76.5 +/- 4.1%, P0.01).Pre-ischemic administration of low-dose PGE(1) in rats provided neuroprotection against severe forebrain ischemia. A dose dependency was not observed with PGE(1) dose and outcome.

Background Dexmedetomidine (Dex) provides sedation and analgesia by acting on central alpha-2 receptors and is suitable for use after extubation because it has little respiratory depression. Considering the sympathoinhibitory and anxiolytic action of Dex, there is the possibility that Dex might reduce the incidence of atrial fibrillation (AF), which is recognized as a common complication after cardiovascular surgery. We investigated whether the postoperative incidence of AF decreased in patients who received Dex only during the nighttime in the intensive care unit (ICU). Methods We retrospectively reviewed ICU charts to determine the incidence of AF and associated factors during the 2-day period after tracheal extubation in patients who underwent cardiovascular surgery from November 2009 to November 2010. The patients were divided into a Dex group (n = 16) and a non-Dex group (n = 29). Results There were no differences in AF risk factors except for diabetes between the two groups. The average rate of Dex administration was 0.3 ± 0.2 μg/kg/h. There were also no differences between the groups in heart rate during the daytime, central venous pressure, body temperature, white blood cell count, serum level of C-reactive protein, catecholamine use, beta-blocker use, and amount of fentanyl. AF developed in one patient in the Dex group (6.3 %) and ten patients in the non-Dex group (34.5 %) during the observation period, and the difference was significant (p = 0.035). None of the risk factors for AF was significantly associated with AF in univariate analysis; however, multivariate logistic regression analysis using age, Dex use, and beta-blocker use, extracted because their p values in univariate analysis were not exceeding 0.15, showed that Dex use was the only factor associated with the development of AF (p = 0.045, odds ratio 9.75 [1.05–90.8]). Conclusions The results suggest that adequate sedation with Dex during the nighttime can reduce the incidence of AF in cardiovascular surgery patients after extubation.

Isoflurane improves outcome against cerebral ischemia in the rat. However, the optimal neuroprotective concentration has not been defined. We examined the effects of different isoflurane concentrations on outcome from severe forebrain ischemia in the rat. Fasted rats were subjected to 0.5, 1.0, 1.5, 2.0, or 2.5 minimum alveolar concentration (MAC) isoflurane during 10 min bilateral carotid occlusion plus systemic hypotension. Each isoflurane concentration was administered only before ischemia. Arterial blood pressure was not pharmacologically manipulated. After ischemia, the anesthetic regimen was changed to fentanyl/nitrous oxide and maintained for 2 h. Pericranial temperature was maintained normothermic during the experiment. Neuromotor score, % dead hippocampal CA1 neurons, and cortical injury were measured 5 days postischemia. Preischemic arterial blood pressure decreased as MAC was increased. Animals administered1.0 MAC frequently exhibited postischemic seizures resulting in increased mortality. There was no difference among MAC conditions for % dead CA1 neurons (93 approximately 95%). In the cortex, neuronal necrosis was less severe with 0.5 MAC and 1.0 MAC isoflurane relative to1.0 MAC values. The neuromotor score in the 1.0 MAC isoflurane group was superior to the 2.5 MAC group. Dose-dependent effects of preischemic administration of isoflurane on histologic and behavioral outcome after severe forebrain ischemia were observed. Isoflurane MAC values1.5 provided superior overall outcome relative to larger isoflurane concentrations.

Manipulations of plasma catecholamine concentrations influence outcome from ischemic brain insults. It has been suggested that these effects are mediated by influences on brain catecholamine concentrations. This study examined whether major changes in brain norepinephrine concentrations can alter outcome from severe forebrain ischemia. Sprague-Dawley rats were administered 50 mg/kg i. p. N-(chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) or were left untreated (control). One week later, these rats were subjected to either 7 or 8 min of normothermic forebrain ischemia (bilateral carotid occlusion and MABP=30 mmHg) and allowed to recover for 4 days. Histologic damage was then evaluated. In other control and DSP-4-treated animals, hippocampal microdialysate norepinephrine concentrations were measured before, during and after 8 min of forebrain ischemia. Norepinephrine concentrations were also determined in brain homogenates from non-ischemic DSP-treated and control rats. A 95% depletion of norepinephrine was observed in brain homogenates from non-ischemic DSP-4-treated rats compared with control. During ischemia, microdialysate norepinephrine concentrations increased in control but not in DSP-4-treated rats (P=0.002). For plasma, intra-ischemic epinephrine concentrations increased 8-10-fold and returned to baseline values post-ischemia with no differences between groups. Plasma norepinephrine values remained unchanged in both groups. Histologic damage resulting from either 7 or 8 min of ischemia in hippocampal structures, caudoputamen, and neocortex was similar between DSP-4-treated and control groups. This study could not identify any effect of major changes in brain norepinephrine concentrations on ischemic brain damage. These data indicate that peripheral catecholamine effects on near-complete forebrain ischemic outcome are unlikely to be mediated by effects on central catecholamine concentrations.

UNLABELLED We postulated that adrenergic responses to global cerebral ischemia are anesthetic-dependent and similar in both brain and arterial blood. Rats were anesthetized with isoflurane (1.4%), ketamine (1 mg x kg(-1) x min(-1)), or fentanyl (25 microg x kg(-1) x h(-1))/70% N2O. The carotid arteries were occluded for either 20 min with mean arterial pressure (MAP) 50 mm Hg (incomplete ischemia) or 10 min with MAP 30 mm Hg (near-complete ischemia). Norepinephrine was measured in hippocampal microdialysate. Norepinephrine and epinephrine were measured in arterial plasma. In both hippocampus and plasma, basal norepinephrine was similar among anesthetics. During incomplete ischemia, hippocampal norepinephrine was twofold greater with fentanyl/N2O than with isoflurane (P = 0.037), but plasma norepinephrine and epinephrine were similar and unchanged among all three anesthetics. During near-complete ischemia, hippocampal norepinephrine was threefold greater with ketamine than fentanyl/N2O (P = 0.005), whereas plasma norepinephrine and epinephrine were markedly greater with fentanyl/N2O than with ketamine (P < 0.0005) or isoflurane (P = 0.05). There was no correlation between norepinephrine concentrations in hippocampus and plasma for either incomplete or near-complete ischemia. This study demonstrates that adrenergic responses to global ischemia are anesthetic-dependent, particularly during more severe insults. The absence of a correlation between plasma and brain catecholamine concentrations indicates that adrenergic responses to ischemia are independent in brain and blood. IMPLICATIONS It has been proposed that anesthetics modulate cerebral ischemic outcome by influencing peripheral adrenergic responses to ischemia. This experiment demonstrates that anesthetics differentially modulate adrenergic responses to ischemia but that effects in plasma and brain are independent. This suggests that events detected in the peripheral circulation do not implicate direct mechanisms of action of catecholamines at the neuronal/glial level.

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)

64歳女性の膵頭十二指腸切除術(診断;膵頭部嚢胞腺癌)の麻酔管理を,持続硬膜外麻酔および笑気-酸素-イソフルランで行なった。手術操作に伴い血圧が上昇し,その管理は困難であった。カテコラミン産生腫瘍が疑われ,病理診断でパラガングリオーマと診断された。このような症例はまれではあるが,万一遭遇した場合には術中管理に難渋する。したがって,確定診断のついていない後腹膜腫瘍の麻酔管理に際しては,迅速な循環管理が行なえるよう十分な準備が必要であると思われた。

previously. A routine chest roentgenogram taken during an annual check-up showed a suspicious shadow. The patient was referred to another hospital for a complete medical evaluation. Left lung cancer was diagnosed. His electrocardiogram (ECG) showed a negative T wave in leads V5 and V6, indicating a pattern of old septal and inferior myocardial infarction with mild left ventricular (LV) hypertrophy. Furthermore, epicardial echocardiography (EE) revealed interventricular septal hypertrophy (ISH) and LV outflow hypertrophy, without deterioration of LV wall motion but with mild mitral regurgitation (MR). His cardiac index (CI), ejection fraction (EF), and EE-derived LV-Ao PG were 3.85 l·min 1·m 2, 86%, and 72 mmHg, respectively. Finally, HOCM accompanied with MR were diagnosed. The patient was scheduled for right upper lobectomy in the same hospital without any specific medical treatment for HOCM prior to surgery. The patient was premedicated with intramuscular atropine (0.5 mg) and hydroxyzine (50mg) prior to the induction of anesthesia. On arrival at the operating theater, his heart rate was 78 beats·min 1, and his systolic and diastolic blood pressure showed 132/86mmHg. After the placement of an epidural catheter via the thoracic segment T8/9, anesthesia was induced with bolus intravenous (iv) fentanyl (0.8μg·kg 1) and propofol (1mg·kg 1), as well as with continuous infusion of propofol (10mg·kg 1·h 1), followed by vecuronium (0.03 mg·kg 1). Hypotension (60 mmHg) and profound bradycardia (35 beats·min 1) were observed after anesthesia was induced. Hypotension was controlled rapidly both by volume replacement and intermittent administration of bolus iv methoxamine (1mg), whereas bradycardia persisted at less than 40 beats·min 1. The anesthetists discontinued the induction of anesthesia and cancelled the operation. Ten minutes later, the heart rate of the patient gradually recovered to a level of 50 beats·min 1. Oral atenolol (50mg·day 1) and disopyramide (300 mg·day 1) were started immediately

This study examined the importance of brain norepinephrine concentration on outcome from a focal ischemic insult. Fasted temperature-controlled male Wistar rats pretreated with DSP-4, (N-(chloroethyl)-N-ethyl-2-bromobenzylamine), to selectively deplete brain norepinephrine, were subjected to reversible filament occlusion of the middle cerebral artery for 75 min in the awake state. After 3 days recovery, total infarct volume in DSP-4 treated rats (185 +/- 107 mm3) was reduced vs. untreated control animals (242 +/- 71 mm3, P = 0.04). Subcortical infarct volume was also smaller in the DSP-4 group (93 +/- 44 vs. 121 +/- 28 mm3, P = 0.02). Cortical infarct volume was not statistically different between groups. Neurologic function correlated with infarct-size. These findings suggest that brain norepinephrine affects stroke development either by direct neuronal toxicity and/or through influences on the penumbral circulation. Dampening of the central stress response induced by the onset of stroke may thus be advantageous.

Background Isoflurane-anesthetized rats have better outcome from global cerebral ischemia than rats anesthetized with fentanyl and nitrous oxide. The authors wanted to determine whether circulating catecholamine concentrations depend on the anesthetic agent and whether sympathetic ganglionic blockade affects anesthetic-mediated differences in outcome from near-complete forebrain ischemia. Methods For two different experiments, normothermic Sprague-Dawley rats that had fasted were assigned to one of four groups and subjected to 10 min of 30 mm Hg mean arterial pressure and bilateral carotid occlusion. Rats were anesthetized with 1.4% isoflurane or fentanyl (25 microg x kg(-1) x h(-1)) and 70% nitrous oxide, with or without preischemic trimethaphan (2.5 mg given intravenously). In experiment 1, arterial plasma catecholamine concentrations were measured before, at 2 and 8 min during, and after ischemia (n = 5-8). In experiment 2, animals (n = 15) underwent histologic analysis 5 days after ischemia. Results In experiment 1, intraischemic increases in plasma norepinephrine and epinephrine levels were 28 and 12 times greater in the fentanyl-nitrous oxide group than in the isoflurane group (P Conclusions Isoflurane attenuated the peripheral sympathetic response to ischemia and improved histologic outcome compared with fentanyl and nitrous oxide. This outcome benefit was reversed by sympathetic ganglionic blockade. The beneficial effects of isoflurane may result from a neuroprotective influence of an intermediate sympathetic response that is abolished by trimethaphan.

The administration of aprotinin has been associated with a reduction in cardiac surgery-related stroke. Intrinsic neuroprotective properties of this drug have not been evaluated in laboratory outcome models of cerebral ischemia. The purpose of this study was to determine whether aprotinin exhibits neuroprotective effects against either global or focal cerebral ischemia in the rat. Fasted rats were administered aprotinin (30,000 or 60,000 KIU/kg) or vehicle (0.9% NaCl) IV before global ischemia (10 min bilateral carotid occlusion with mean arterial pressure 30 mm Hg) or focal ischemia (75 min of transient middle cerebral artery occlusion [MCAO]). Five days after global ischemia, the percentage of dead hippocampal CA1 neurons (mean +/- SD) was similar among the groups (small-dose aprotinin: 49 +/- 31, n = 15; large-dose aprotinin: 55 +/- 31, n = 13; vehicle: 47 +/- 31, n = 16; P = 0.74). After 7 days' recovery from MCAO, no difference among the groups was observed for either neurologic score (P = 0.99) or cerebral infarct volume (small-dose aprotinin: 136 +/- 80 mm (3), n = 23; large-dose aprotinin: 132 +/- 101 mm3, n = 11; vehicle: 121 +/- 81 mm3, n = 21; P = 0.87). Implications: Aprotinin offers no neuroprotection against either global or focal cerebral ischemia in the rat when administered as a single preischemic bolus. (Anesth Analg 1999;88:1-7)

Background It has been postulated that anesthetic agents that reduce cerebral metabolic rate will protect the brain against ischemia when electroencephalographic (EEG) activity is persistent, but will provide no protection when ischemia is severe enough to cause EEG isoelectricity. No outcome studies have addressed this issue. The authors studied anesthetic agents to determine if they provide differential effects on outcome from global cerebral ischemic insults that cause either an attenuated or isoelectric EEG. Methods Fasted rats were subjected to either (1) incomplete ischemia (attenuated EEG; 20 min of mean arterial pressure [MAP] = 50 mmHg and bilateral carotid occlusion) or (2) near-complete ischemia (isoelectric EEG; 10 min of MAP = 30 mmHg and bilateral carotid occlusion) while anesthetized with 1.4% isoflurane, 1 mg x kg(-1) x min(-1) ketamine, or 25 microg x kg(-1) x h(-1) 70% nitrous oxide and fentanyl. The brain was maintained at normothermia during ischemia and for 22 h after ischemia. Five days later, hippocampal CA1 and cortical injury were measured. Results There was no difference among anesthetic agents during incomplete ischemia for mean +/- SD percentage dead CA1 neurons (fentanyl, 38%+/-20%; isoflurane, 31%+/-10%; ketamine, 40%+/-19%; P = 0.38). During near-complete ischemia, there was a difference among anesthetic agents (fentanyl, 88%+/-9%; isoflurane, 37%+/-20%; ketamine, 70%+/-28%; P = 0.00008). Isoflurane was protective compared with fentanyl (P = 0.00007) and ketamine (P = 0.0061). There was no difference between fentanyl and ketamine (P = 0.143). Similar observations were made in the cortex. Neurologic function correlated with histologic damage. Conclusions Outcome from near-complete but not incomplete cerebral ischemia depended on the anesthetic agent administered during the ischemic insult.