Satoki Inoue

Low Dose Propofol as a Supplement to Ketamine-Based Anesthesia During Intraoperative Monitoring of Motor-Evoked Potentials

Study Design. Motor-evoked potentials (MEPs) were analyzed using transcranial electrical stimulation during spinal surgery in patients under ketamine-based anesthesia, with and without propofol. Objective. To investigate the effects of propofol on MEPs and ketamine-induced adverse effects during spinal surgery in patients under ketamine-based anesthesia. Summary of Background Data. Intraoperative monitoring of transcranial motor-evoked responses provides a method for monitoring the functional integrity of descending motor pathways. However, because these responses are sensitive to suppression by most anesthetic agents, anesthetic technique is limited during the monitoring of MEPs. Ketamine has been reported to have little effect on MEPs but may produce adverse effects such as psychedelic effect and hypertension. Recently, it has been reported that propofol may be able to inhibit ketamine-induced adverse effects. Methods. Intraoperative monitoring of MEPs was performed in 58 patients who underwent elective spinal surgery. Anesthesia was maintained with nitrous oxide-fentanyl-ketamine without or with low-dose (1–3 mg/kg/hr) of propofol (K group; n = 34, KP group; n = 24, respectively). Transcranial stimulation with single or paired pulses or a train of three or five pulses (interstimulus interval, 2 msec) were delivered to the scalp, and compound muscle action potentials were recorded from the left and right tibialis anterior muscles. To investigate the dose effects of propofol on MEPs, propofol was administered at an infusion rate of 6, 4, and 2 mg/kg/hr and then discontinued in 14 patients. Results. Results of MEPs were comparable between the K and KP groups. The incidence of postoperative psychedelic effect was significantly less in the KP group (14%) than in the K group (41%). Although propofol inhibited MEPs dose dependently, the use of a train of pulses for stimulation could overcome such inhibition. Conclusions. If a train of pulses were used for transcranial stimulation, low-dose propofol can be effectivelyused as a supplement to ketamine-based anesthesia during intraoperative monitoring of myogenic MEPs. Addition of propofol significantly reduced the ketamine-induced psychedelic effects.

Combination of isoflurane and caspase inhibition reduces cerebral injury in rats subjected to focal cerebral ischemia.

Background:Recent data indicate that the neuroprotective efficacy of isoflurane is not sustained. Delayed neuronal death, mediated in part by apoptosis, contributes to the gradual increase in the size of the infarction. These data suggest that isoflurane may not be able to inhibit delayed neuronal death. The prevention of apoptosis by a caspase inhibitor might provide neuroprotection in addition to that provided by isoflurane. The current study was conducted to determine whether isoflurane-mediated neuroprotection can be made more durable with the administration of z-VAD-fmk, a nonspecific caspase inhibitor. Methods:Fasted Wister rats were allocated to awake–zVAD, awake–vehicle, isoflurane–zVAD, or isoflurane–vehicle groups (n = 16/group). Animals were subjected to focal ischemia for 60 min by filament occlusion of the middle cerebral artery. In the awake groups, isoflurane was discontinued after occlusion of the middle cerebral artery. In the isoflurane groups, isoflurane anesthesia was maintained at 1.5 minimum alveolar concentration during occlusion of the middle cerebral artery. Before and after ischemia, daily injections of z-VAD-fmk or vehicle were administered into the lateral cerebral ventricle for 14 days. Neurologic assessment was performed 14 days after ischemia. The volume of cerebral infarction and the number of intact neurons in the periinfarct cortex were determined by image analysis of hematoxylin and eosin–stained coronal brain sections. Results:Infarction volume was less in the isoflurane–zVAD group (23 ± 11 mm3, mean ± SD) than in isoflurane–vehicle, awake–vehicle, and awake–zVAD groups (82 ± 31, 86 ± 31, and 59 ± 25 mm3, respectively; P < 0.05). In comparison with the awake–vehicle and isoflurane–vehicle groups, the administration of z-VAD-fmk significantly decreased infarction volume (P < 0.05). The infarction volume between the awake–vehicle and isoflurane–vehicle groups was not different. The number of intact neurons within the periinfarct cortex was significantly less in the awake–vehicle group than in the other three groups (P < 0.05). The isoflurane–zVAD group demonstrated better neurologic function than the awake–vehicle group (P < 0.05). Conclusion:These findings are consistent with the premise that ongoing delayed neuronal death, in part mediated by apoptosis, contributes to the progression of cerebral infarction during the recovery period, and its inhibition can provide sustained neuroprotection.

Evaluation of Rapid Ischemic Preconditioning in a Rabbit Model of Spinal Cord Ischemia

Background Rapid ischemic preconditioning (IPC) has been shown to reduce cellular injury after subsequent cardiac and cerebral ischemia. However, the data on rapid IPC of the spinal cord is limited. The authors investigated whether pretreatment with sublethal ischemia of spinal cord can attenuate neuronal injury after spinal cord ischemia in rabbits. Methods Forty-seven male New Zealand white rabbits were randomly assigned to one of three groups (n = 15 or 16 each). In the IPC(−) group, the infrarenal aorta was occluded for 17 min to produce spinal cord ischemia. In the IPC(+) group, 5 min of aortic occlusion was performed 30 min before 17 min of spinal cord ischemia. In the sham group, the aorta was not occluded. Hind limb motor function was assessed at 3 h, 24 h, 4 days, and 7 days after reperfusion using Tarlov scoring (0 = paraplegia; 4 = normal). Animals were killed for histopathologic evaluation at 24 h or 7 days after reperfusion. The number of normal neurons in the anterior spinal cord (L4–L6) was counted. Results Neurologic scores were significantly higher in the IPC(+) group than the IPC(−) group at 3 and 24 h after reperfusion (P < 0.05). However, neurologic scores in the IPC(+) group gradually decreased and became similar to those in the IPC(−) group at 4 and 7 days after reperfusion. At 24 h after reperfusion, the numbers of normal neurons were significantly higher in the IPC (+) group than in the IPC(−) group (P < 0.05) and were similar between the IPC(+) and sham groups. At 7 days after reperfusion, there was no difference in the number of normal neurons between the IPC(+) and IPC(−) groups. Conclusion The results indicate that rapid IPC protects the spinal cord against neuronal damage 24 h but not 7 days after reperfusion in a rabbit model of spinal cord ischemia, suggesting that the efficacy of rapid IPC may be transient.

The effect of sevoflurane on myogenic motor-evoked potentials induced by single and paired transcranial electrical stimulation of the motor cortex during nitrous oxide/ketamine/fentanyl anesthesia.

To overcome anesthetic-induced depression of myogenic motor-evoked potentials (MEPs), several techniques of stimulation using paired pulses or trains of pulses are used. This study investigated the effect of sevoflurane on myogenic MEPs induced by single and paired transcranial electrical stimulation of the motor cortex. Nine patients undergoing elective spinal surgery were anesthetized with fentanyl-N2O-ketamine. Partial neuromuscular blockade (single-twitch height 15% of baseline) was maintained with vecuronium. Single and paired (interstimulus interval 2 milliseconds) electrical stimuli were delivered to the scalp, and compound muscle action potentials were recorded from the left and right tibialis anterior muscles. In all patients, baseline MEPs were recorded from both the left and right anterior tibialis muscles (in a total of 18 legs). During the administration of 0.25 MAC and 0.5 MAC sevoflurane, MEPs induced by stimulation with a single pulse could be recorded in 12 of 18 and 4 of 18 legs, respectively, and MEP amplitude was significantly reduced to 48% and 4% of the control value, respectively. During the administration of 0.75 MAC sevoflurane, MEPs following single-pulse stimulation could not be recorded in any legs. The success rate of MEP recording during the administration of sevoflurane was greater after paired stimulation than after single stimulation, and percentage MEP amplitude (percentage of the control value after single stimulation but before sevoflurane) after paired stimulation was significantly higher than after single stimulation before and during the administration of 0.25 MAC and 0.5 MAC sevoflurane. The success rate of MEP recording and MEP amplitude after paired stimulation decreased in a dose-dependent manner during the administration of sevoflurane. These results suggest that although facilitation by the second stimulus was considerable, paired stimuli are still not sufficient to overcome the depressant effects of sevoflurane in clinically used concentrations.

Jugular bulb oxygen saturation under propofol or sevoflurane/nitrous oxide anesthesia during deliberate mild hypothermia in neurosurgical patients.

Sevoflurane and propofol have been widely used as anesthetic agents for neurosurgery. Recent evidence has suggested that the influence of these anesthetics on cerebral oxygenation may differ. In the present study, the authors investigated jugular bulb oxygen saturation (SjO2) during propofol and sevoflurane/nitrous oxide anesthesia under mildly hypothermic conditions. After institutional approval and informed consent, 20 patients undergoing elective craniotomy were studied. Patients were randomly divided to the group S/N2O (sevoflurane/nitrous oxide/fentanyl anesthesia) or the group P (propofol/fentanyl anesthesia). After induction of anesthesia, the catheter was inserted retrograde into the jugular bulb and SjO2 was analyzed. During the operation, patients were cooled and tympanic membrane temperature was maintained at 34.5°C. SjO2 was measured at normocapnia during mild hypothermia and at hypocapnia during mild hypothermia. There were no statistically significant differences in demographic variables between the groups. During mild hypothermia, SjO2 values were significantly lower in group P than in group S/N2O. The incidence of SjO2 less than 50% under mild hypothermic-hypocapnic conditions was significantly higher in group P than in group S/N2O. These results suggest that hyperventilation should be more cautiously applied during mild hypothermia in patients anesthetized with propofol and fentanyl versus sevoflurane/nitrous oxide/fentanyl.

The association of high jugular bulb venous oxygen saturation with cognitive Decline after hypothermic cardiopulmonary bypass

This study was conducted to investigate whether jugular bulb venous oxygen saturation (Sjvo2) predicted cognitive decline after cardiac surgery with hypothermic cardiopulmonary bypass (CPB). We studied 35 patients undergoing cardiac surgery. After the induction of anesthesia, a 5.5F fiberoptic oximetry catheter was retrogradely inserted into the jugular bulb, and Sjvo2 and other cerebral oxygenation variables were analyzed before, during, and after CPB. At each point, an oxyhemoglobin dissociation curve was drawn, and the P50 value of jugular bulb venous blood was calculated by computer analysis. Cognitive function was assessed with the revised version of Hasegawa’s Dementia Scale and the Benton Revised Visual Retention Test before and early after the operation. In 15 patients (the Decline group), cognitive function was declined after surgery, whereas it remained unchanged in 20 patients (the Normal group). Sjvo2 was significantly higher and cerebral oxygen extraction was significantly lower before and during CPB in the Decline group than in the Normal group (P < 0.05). The oxygen pressure at an oxygen saturation of 50% was significantly lower before and after CPB in the Decline group than in the Normal group (P < 0.05). Logistic regression analysis showed that high Sjvo2 was a predictor of cognitive decline after cardiac surgery. We conclude that high Sjvo2 was associated with cognitive decline after cardiac surgery with hypothermic CPB.

Tetanic stimulation of the peripheral nerve before transcranial electrical stimulation can enlarge amplitudes of myogenic motor evoked potentials during general anesthesia with neuromuscular blockade

Background: Neuromuscular blockade can suppress myogenic motor evoked potentials (MEPs). The authors hypothesized that tetanic stimulation (TS) of the peripheral nerve before transcranial stimulation may enhance myogenic MEPs during neuromuscular blockade. In the current study, the authors evaluated MEP augmentations by TS at different levels of duration, posttetanic interval, neuromuscular blockade, and stimulus intensity. Methods: Thirty-two patients undergoing propofol–fentanyl–nitrous oxide anesthesia were examined. Train-of-five stimulation was delivered to C3–C4, and MEPs were recorded from the abductor hallucis muscle. In study 1, TS with a duration of 1, 3, or 5 s was delivered at 50 Hz to the tibial nerve 1, 3, or 5 s (interval) before transcranial stimulation, and the effects of TS on MEP amplitude were evaluated. In study 2, TS-induced MEP augmentations were evaluated at the neuromuscular blockade level (%T1) of 50% or 5%. In study 3, MEP augmentations by TS at stimulus intensities of 0, 5, 25, and 50 mA were evaluated. Results: The application of TS significantly enlarged the amplitudes of MEPs at the combinations of duration (3, 5 s) and interval (1, 3, 5 s) compared with those without TS. TS-induced MEP augmentations were similarly observed at %T1 of both 50% and 5%. TS-induced MEP augmentations were observed at stimulus intensities of 25 and 50 mA. Conclusions: The results indicate that TS of the peripheral nerve before transcranial stimulation can enlarge the amplitude of MEPs during general anesthesia with neuromuscular blockade. TS of the peripheral nerve can be intraoperatively applied as a method to augment myogenic MEP responses.

Increased plasma concentration of adrenomedullin in patients with subarachnoid hemorrhage.

Adrenomedullin (AM) is a potent hypotensive peptide originally identified in pheochromocytoma tissues.Impaired cardiovascular conditions, such as hypertension, myocardial infarction, and septic shock, stimulate production of AM. This study was performed to determine whether subarachnoid hemorrhage (SAH) altered plasma AM concentration. Plasma concentrations of AM in 17 patients with SAH were measured for 2 wk after the onset of SAH by AM-specific radioimmunoassay. Plasma concentrations of AM were increased in patients with SAH throughout the study period, compared with those in control subjects. Plasma concentrations of AM in patients classified as Hunt and Kosnik grade III or IV were significantly higher than those classified as Hunt and Kosnik grade I or II on the day of and the day after the onset of SAH. However, plasma concentrations of AM were unaffected by angiographic vasospasm. These findings suggest that plasma concentrations of AM are increased in patients with SAH and may reflect the severity of SAH. Implications: Adrenomedullin has been reported to affect the cerebral circulation. This study was performed to determine whether subarachnoid hemorrhage, a typical cerebrovascular disorder, altered plasma adrenomedullin concentrations. We found that plasma adrenomedullin concentrations increased in patients with subarachnoid hemorrhage, although no relationship was found between plasma adrenomedullin concentration and angiographic vasospasm. Plasma adrenomedullin concentration may reflect the severity of hemorrhage. (Anesth Analg 1998;87:859-63)

The combination of isoflurane and caspase 8 inhibition results in sustained neuroprotection in rats subject to focal cerebral ischemia.

Although isoflurane can reduce ischemic neuronal injury after short postischemic recovery intervals, data from our laboratory have demonstrated that this neuroprotection is not sustained and that delayed apoptotic neuronal death, mediated in part by activation of caspases, contributes to the gradual increase in the size of the infarction. We tested the hypothesis that the neuroprotective efficacy of isoflurane can be prolonged with the administration of z-IETD-fmk, a specific inhibitor of caspase 8. Fasted Wister rats were anesthetized with isoflurane and randomly allocated to awake-vehicle, isoflurane-vehicle, awake-IETD, or isoflurane-IETD groups (n = 25 per group). Animals were subjected to 60 min focal ischemia by filament occlusion of the middle cerebral artery (MCAO). Daily intracerebroventricular injections of z-IETD-fmk or vehicle were administered via an implanted cannula starting before ischemia and continuing until 14 days post-MCAO. Neurological assessment was performed 14 days after ischemia after which the volume of cerebral infarction and number of intact neurons in the peri-infarct cortex were determined. Total infarction volume was less in the isoflurane-IETD group than in awake-vehicle, isoflurane-vehicle, and awake-IETD groups. Infarction volume was also less in the awake-IETD group versus the awake-vehicle group. The number of intact neurons within the peri-infarct cortex was significantly less in the awake-vehicle group in comparison with the other three experimental groups. The isoflurane-IETD group had better neurologic outcomes than both vehicle-treated groups at 14 days post-MCAO. These results suggest that a combination of isoflurane and a caspase 8 inhibitor can produce neuroprotection that is evident even after a recovery period of 14 days. This combination demonstrated greater efficacy than the administration of either isoflurane or z-IETD-fmk alone. These results are consistent with the premise that continuing apoptosis contributes to the enlargement of cerebral infarction during the recovery period and that its inhibition can provide sustained neuroprotection.

The Effects of β-adrenoceptor Antagonists on Proinflammatory Cytokine Concentrations After Subarachnoid Hemorrhage in Rats

BACKGROUND: Proinflammatory cytokines increase in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). Recent evidence suggested that &bgr;-adrenoceptor antagonist could reduce proinflammatory cytokines. We conducted the present study to examine whether &bgr;-adrenoceptor antagonists would reduce proinflammatory cytokine concentrations after SAH in rats. METHODS: In Experiment 1, to investigate the time course of interleukin-6 (IL-6) and tumor necrosis factor-&agr; (TNF-&agr;), rats were randomized into groups: 1, 3, 6, and 12 h after SAH or sham operation. CSF and blood samples were obtained at each time point. In Experiment 2, to investigate the effects of &bgr;-adrenoceptor antagonists on the IL-6 and TNF-&agr; concentrations, rats were randomized into groups: 1) control group: SAH + normal saline, 2) propranolol group: SAH + propranolol, 3) metoprolol group: SAH + metoprolol, and 4) butoxamine group: SAH + butoxamine (&bgr;2-adrenoceptor antagonist). CSF and blood samples were obtained 6 h after SAH. IL-6 and TNF-&agr; concentrations in samples were measured. RESULTS: In Experiment 1, CSF IL-6 concentrations in the SAH groups increased markedly and peaked at 6 h after SAH, whereas CSF TNF-&agr; concentrations in the SAH groups were consistently low. In Experiment 2, CSF IL-6 concentrations in the propranolol and butoxamine groups were significantly lower compared with those in the control group (P < 0.01 and P < 0.05 for each group). Plasma IL-6, CSF TNF-&agr;, and plasma TNF-&agr; concentrations were comparable in all four groups. CONCLUSIONS: CSF IL-6 concentrations increased in the acute stage of SAH and &bgr;-adrenoceptor antagonists with a &bgr;2-adrenoceptor blocking action suppressed this elevation of IL-6 concentrations after SAH in rats.