Meiko Kakimoto

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.

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.

The influence of induced hypothermia for hemostatic function on temperature-adjusted measurements in rabbits.

In hypothermic patients, a tendency to bleed may be observed even when hemostatic tests seem to be normal. Coagulation and platelet function tests are usually performed at 37°C. We investigated the influence of induced hypothermia on temperature-adjusted hemostasis function testing using Sonoclot Analyzer® (Sonoclot®) and Thromboelastography® (TEG®). Anesthesia was induced and maintained with IV ketamine and fentanyl on 15 male New-Zealand White rabbits. A water blanket was used to induce hypothermia to 30°C and to rewarm to 37°C. Blood samples were obtained at four points: before hypothermia, at 34°C, at 30°C, and after rewarming. Standard coagulation tests were performed at 37°C (C method), and simultaneously, real temperature hemostasis function tests (R method) were run. In Sonoclot®, activated clotting time and time to peak increased and clot rate decreased significantly at 30°C in the R method compared with those in the C method. In TEG®, reaction time and clot formation time were prolonged and clot formation rate was diminished at 30°C in the R method compared with those in the C method. Induced hypothermia delayed the coagulation cascade and reduced platelet function. During hypothermia, hemostatic measurements should be performed at real temperature to avoid overestimating patient hemostatic function based on results measured at the standard 37°C.

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.

Amplitudes and intrapatient variability of myogenic motor evoked potentials to transcranial electrical stimulation during ketamine/N2O- and propofol/N2O-based anesthesia.

The aim of the current study was to investigate whether there are differences in amplitudes and intrapatient variability of motor evoked potentials to five pulses of transcranial electrical stimulation between ketamine/N2O- and propofol/N2O-based anesthesia. Patients in the propofol group (n = 13) and the ketamine group (n = 13) were anesthetized with 50% N2O in oxygen, fentanyl, and 4 mg/kg/hr of propofol or 1 mg/kg/hr of ketamine, respectively. The level of neuromuscular blockade was maintained at an M-response amplitude of approximately 50% of control. Motor evoked potentials in response to multipulse transcranial electrical stimulation were recorded from the right adductor pollicis brevis muscle, and peak-to-peak amplitude and onset latency of motor evoked potentials were evaluated. To estimate intrapatient variability, the coefficient of variation (standard deviation/mean × 100%) of 24 consecutive responses was determined. Motor evoked potential amplitudes in the ketamine group were significantly larger than in the propofol group (mean, 10th–90th percentile: 380 &mgr;V, 129–953 &mgr;V; 135 &mgr;V, 38–658 &mgr;V, respectively;P < .05). There were no significant differences in motor evoked potential latency (mean ± standard deviation: 20.9 ± 2.2 msec and 21.4 ± 2.2 msec, respectively) and coefficient of variation of amplitudes (median [range]: 32% [22–42%] and 26% [18–41%], respectively) and latencies (mean ± standard deviation: 2.1 ± 0.7% and 2.1 ± 0.7%, respectively) between the ketamine and propofol groups. In conclusion, intrapatient variability of motor evoked potentials to multipulse transcranial stimulation is similar between ketamine/N2O- and propofol/N2O-based anesthesia, although motor evoked potential amplitudes are lower during propofol/N2O-based anesthesia than ketamine/N2O-based anesthesia.

Reevaluation of gray and white matter injury after spinal cord ischemia in rabbits.

Background:Although gray matter injury has been well characterized, the available data on white matter injury after spinal cord ischemia (SCI) in rabbits are limited. The current study was conducted to investigate the evolution of ischemia induced injury to gray and white matter and to correlate this damage to hind-limb motor function in rabbits subjected to SCI. Methods:Thirty-eight rabbits were randomly assigned to 24-h, 4-day, or 14-day reperfusion groups or a sham group (n = 9 or 10 per group). SCI was induced by occlusion of the infrarenal aorta for 16 min. Hind-limb motor function was assessed using the Tarlov scale (0 = paraplegia, 4 = normal). The gray matter damage was assessed on the basis of the number of normal neurons in the anterior spinal cord. White matter damage was assessed on the basis of the extent of vacuolation and accumulation of amyloid precursor protein immunoreactivity. Results:Tarlov scores gradually decreased and reached a nadir 14 days after reperfusion. There were no significant differences in the number of normal neurons among the 24-h, 4-day, and 14-day groups. The extent of vacuolation, expressed as a percent of total white matter area, was significantly greater in the 4-day and 14-day groups in comparison with the sham group. By contrast, there was no difference in vacuolation between the sham and 24-h groups. Amyloid precursor protein immunoreactivity was greater in the 4-day and 14-day groups. Conclusion:The results in the current study show that SCI induced white matter injury as well as gray matter injury in a rabbit model of SCI. The time course for 14 days after reperfusion may differ among the gray and white matter damages and hind-limb motor function in rabbits subjected to SCI.

The effects of dexmedetomidine on myogenic motor evoked potentials in rabbits.

BACKGROUND:Dexmedetomidine is used in the perioperative management of patients, including as an intraoperative adjuvant. The effects of dexmedetomidine on myogenic motor evoked potentials (MEPs) remain undetermined. We conducted the present study to investigate the effects of dexmedetomidine on myogenic MEPs in rabbits. METHODS:New Zealand white rabbits were used for the studies. First, to determine appropriate doses of dexmedetomidine as an adjunct for anesthesia in rabbits, the level of anesthesia was evaluated by testing the palpebral and limb withdrawal reflexes, and the reactions to ear pinching and tail clamp at 5, 25, 50, 100 &mgr;g/kg/h. Second, in 10 rabbits under ketamine and fentanyl anesthesia, myogenic MEPs in response to single pulse and a train-of-five pulses were recorded from the soleus muscle before, during, and after the administration of dexmedetomidine at 5, 25, and 50 &mgr;g/kg/h. RESULTS:At 50 &mgr;g/kg/h of dexmedetomidine, palpebral reflex, limb reflex, and reaction to ear pinching were inhibited in >50% of animals, but the reaction to tail clamp was not reduced. Dexmedetomidine suppressed myogenic MEPs in a dose-dependent manner, but when multipulses were used for stimulation, myogenic MEPs could be recorded in all animals at 50 &mgr;g/kg/h. CONCLUSIONS:As long as multipulse is used for stimulation, the recording of myogenic MEPs is feasible in rabbits under ketamine and fentanyl anesthesia during the administration of dexmedetomidine at doses that are an adjunct to anesthesia.

Long-term assessment of hind limb motor function and neuronal injury following spinal cord ischemia in rats.

Recent evidence suggests that brain injury caused by ischemia is a dynamic process characterized by ongoing neuronal loss for at least 14 days after ischemia. However, long-term outcome following spinal cord ischemia has not been extensively examined. Therefore, we investigated the changes of hind limb motor function and neuronal injury during a 14-day recovery period after spinal cord ischemia. Male Sprague-Dawley rats received spinal cord ischemia (n = 64) or sham operation (n = 21). Spinal cord ischemia was induced by inflation of a 2F Fogarty catheter placed into the thoracic aorta for 6, 8, or 10 minutes. The rats were killed 2, 7, or 14 days after reperfusion. Hind limb motor function was assessed with the 21-point Basso, Beattie, and Bresnahan (BBB) scale during the recovery period. The number of normal and necrotic neurons was counted in spinal cord sections stained with hematoxylin/eosin. Longer duration of spinal cord ischemia produced severer hind limb motor dysfunction at each time point. However, BBB scores gradually improved during the 14-day recovery period. Neurologic deterioration was not observed between 7 and 14 days after reperfusion. The number of necrotic neurons peaked 2 days after reperfusion and then decreased. A small number of necrotic neurons were still observed 7 and 14 days after reperfusion in some of the animals. These results indicate that, although hind limb motor function may gradually recover, neuronal loss can be ongoing for 14 days after spinal cord ischemia.

Effects of xenon on ischemic spinal cord injury in rabbits: a comparison with propofol.

Background: Xenon has been shown to reduce cellular injury after cerebral ischemia. However, the neuroprotective effects of xenon on ischemic spinal cord are unknown. The authors compared the effects of xenon and propofol on spinal cord injury following spinal cord ischemia in rabbits.