Sakahiro Ikeda

Sevoflurane causes greater QTc interval prolongation in elderly patients than in younger patients.

BACKGROUND: Sevoflurane and droperidol prolong the QT interval, and advancing age is not only associated with a prolongation of the QT interval but is also a risk factor for drug-induced QT interval prolongation. In this study, we compared the effect of sevoflurane and droperidol on the corrected QT (QTc) interval and the dispersion of ventricular repolarization (time interval from the peak to the end of the T wave [Tp-e]) in elderly patients with those in younger patients. METHODS: Under sevoflurane anesthesia (1.5%–2.5%) with an antiemetic dose of droperidol (1.25 mg), the QT interval and the Tp-e interval, which indicates transmural dispersion of repolarization across the myocardial wall, were measured in 30 elderly patients (70 years and older) and in 30 younger patients (20–69 years) for 2 hours. The QT interval was normalized for heart rate (QTc) using 3 different formulas: Bazett, Matsunaga, and Van de Water. Data are presented as mean ± sd. RESULTS: The elderly group was 24.4 years older (P < 0.05) than the younger group. The QTc intervals in the 2 groups before anesthesia were not significantly different. Using all 3 formulas, the QTc interval in the elderly patient group was significantly prolonged by sevoflurane (the QTc intervals at preanesthesia and 60, 75, 90, and 120 minutes after sevoflurane exposure were 0.434 ± 0.028 seconds, 0.450 ± 0.037 seconds, 0.463 ± 0.037 seconds, 0.461 ± 0.037 seconds, and 0.461 ± 0.038 seconds, respectively, with the Bazett formula). The sevoflurane-induced QTc interval prolongation in the elderly patient group was significantly greater than that in the younger patient group (0.450 ± 0.037 seconds vs 0.432 ± 0.034 seconds, 60 minutes after sevoflurane exposure; 0.463 ± 0.037 seconds vs 0.441 ± 0.037 seconds, 75 minutes after sevoflurane exposure; and 0.461 ± 0.038 seconds vs 0.436 ± 0.030 seconds, 120 minutes after sevoflurane exposure with the Bazett formula), but the sevoflurane-induced QTc interval prolongation was neither further enhanced with time nor by droperidol. The Tp-e interval was not affected in either group. CONCLUSION: Sevoflurane causes greater QTc interval prolongation in elderly patients than in younger patients. Although sevoflurane does not affect the transmural dispersion of repolarization and sevoflurane-induced QTc prolongation does not advance with time and by droperidol administration, QT interval prolongation and its associated arrhythmias should be carefully monitored during sevoflurane anesthesia in elderly patients.

The anticonvulsant effects of volatile anesthetics on penicillin-induced status epilepticus in cats.

Volatile anesthetics may be used to treat status epilepticus when conventional drugs are ineffective. We studied 30 cats to compare the inhibitory effects of sevoflurane, isoflurane, and halothane on penicillin-induced status epilepticus. Anesthesia was induced and maintained with one of the three volatile anesthetics in oxygen. Penicillin G was injected into the cisterna magna, and the volatile anesthetic discontinued. Once status epilepticus was induced (convulsive period), the animal was reanesthetized with 0.6 minimum alveolar anesthetic concentration (MAC) of the volatile anesthetic for 30 min, then with 1.5 MAC for the next 30 min. Electroencephalogram and multiunit activity in the midbrain reticular formation were recorded. At 0.6 MAC, all anesthetics showed anticonvulsant effects. Isoflurane and halothane each abolished the repetitive spike phase in one cat; isoflurane reduced the occupancy of the repetitive spike phase (to 27% ± 22% of the convulsive period (mean ± SD) significantly more than sevoflurane (60% ± 29%;P < 0.05) and halothane (61% ± 24%;P < 0.05), and the increase of midbrain reticular formation with repetitive spikes was reduced by all volatile anesthetics. The repetitive spikes were abolished by 1.5 MAC of the anesthetics: in 9 of 10 cats by sevoflurane, in 9 of 9 cats by isoflurane, and in 9 of 11 cats by halothane. In conclusion, isoflurane, sevoflurane, and halothane inhibited penicillin-induced status epilepticus, but isoflurane was the most potent. Implications Convulsive status epilepticus is an emergency state and requires immediate suppression of clinical and electrical seizures, but conventional drugs may be ineffective. In such cases, general anesthesia may be effective. In the present study, we suggest that isoflurane is preferable to halothane and sevoflurane to suppress sustained seizure.

Expression of murine novel zinc finger proteins highly homologous to Drosophila ovo gene product in testis

We have cloned two isoforms of cDNAs encoding novel zinc finger proteins. One form encodes a 274‐amino acid protein containing an acidic amino acid and serine‐rich domain and a zinc finger domain which shows high sequence homology to that of Drosophila Ovo protein. The other form encodes a 179‐amino acid protein containing only the zinc finger domain. Expression of both proteins possessing an antigenic epitope in COS cells revealed that they are localized in the nucleus. The 1.3‐kbp mRNAs are predominantly expressed in testis, and the expression increases from 3 weeks postnatal, implying that these proteins may play important roles in the development of the testes.

The anticonvulsant effects of volatile anesthetics on lidocaine-induced seizures in cats

Large concentrations of sevoflurane and isoflurane, but not halothane, induce spikes in the electroencephalogram. To elucidate whether these proconvulsant effects affect lidocaine-induced seizures, we compared the effects of sevoflurane, isoflurane, and halothane in cats. Fifty animals were allocated to 1 of 10 groups: 70% nitrous oxide (N2O), 0.6 minimum alveolar anesthetic concentration (MAC) + 70% N2O, 1.5 MAC + 70% N2O, and 1.5 MAC of each volatile agent in oxygen. Lidocaine 4 mg · kg−1 · min−1 was infused IV under mechanical ventilation with muscle relaxation. Electroencephalogram in the cortex, amygdala, and hippocampus and multiunit activities in the midbrain reticular formation (R-MUA) were recorded. Lidocaine induced spikes first from the amygdala or hippocampus in the 70% N2O and halothane groups and from the cortex in the sevoflurane and isoflurane groups. Lidocaine induced seizures in all cats in the 70% N2O and 0.6 MAC + N2O groups. Seizure occurrence was reduced in the 1.5 MAC + N2O group (P < 0.05 versus 70% N2O). The onset of seizure was delayed in the 0.6 MAC + N2O and 1.5 MAC groups for sevoflurane and isoflurane, but not for halothane, compared with the 70% N2O group (P < 0.05). Lidocaine increased R-MUA with seizure by 130% ± 56% in the 70% N2O group. The increase of R-MUA with seizure was more suppressed in the volatile anesthetic groups than in the 70% N2O group (P < 0.05). In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased. Implications Increasingly, epidural blockade is combined with general anesthesia to achieve stress-free anesthesia and continuous pain relief in the postoperative period. In the present study, sevoflurane and isoflurane attenuated seizure when the blood lidocaine concentration was accidentally increased.

Cloning and characterization of two novel aldo‐keto reductases (AKR1C12 and AKR1C13) from mouse stomach

In contrast to hepatic hydrosteroid dehydrogenases (HSDs) of the aldo‐keto reductase family (AKR1C), little is known about a stomach one. From a mouse stomach cDNA library, we isolated two clones encoding proteins of 323 amino acid residues. They exhibited 93.2% amino acid sequence identity and 64–68% with any known HSDs. Recombinant proteins expressed in Escherichia coli reduced 9,10‐phenanthraquinone with NAD(P)H as cofactor. The mRNAs were exclusively expressed in stomach, liver and ileum. The present study demonstrates that these proteins are new members of the HSD subfamily and they are named AKR1C12 and AKR1C13. Immunohistochemical analysis suggests that they are involved in detoxification of xenobiotics in the stomach.

Suppressive actions of volatile anaesthetics on the response capability in cats

PurposeSuppression of response to a given stimulus by anaesthetics might be considered as a summation of the suppression of basal (pre-stimulus) activity and response capability (increased by stimulus). Anaesthetic suppression of each component in brain and cardiovascular variables by halothane, isoflurane or sevoflurane was compared in cats.MethodsThirty cats were allocated to one of three groups (n = 10 in each) according to the anaesthetic given. The sciatic nerve was stimulated after maintaining the end-tidal concentration of the anaesthetic at 1.3 or 2.0 MAC for at least 30 min. Cortical electroencephalogram (EEG), multi-unit activity in the mid-brain reticular formation (R-MUA), mean arterial pressure (MAP) and heart rate (HR) were measured before and after electrical sciatic nerve stimulation.ResultsThe EEG patterns and R-MUA indicated greater suppression of activity in the brain by isoflurane (31 ±4% of awake state at 1.3 MAC, mean ± SEM) and sevoflurane (38 ± 5%) than by halothane (61 ± 5%,P < 0.05), before stimulation. The R-MUA following the stimulation was not different among agents. The MAP and HR were not different among groups before stimulation, but following stimulation were greater in the sevoflurane group (137 ± 9 and 103 ± 9 mmHg at 1.3 and 2.0 MAC) than in the halothane group (103 ± 5 and 76 ± 3 mmHg,P < 0.05).ConclusionIsoflurane and sevoflurane have greater suppressive action on the basal CNS activity than halothane at the same MAC, and that these two anaesthetics have a weak suppressive action on the response capability to peripheral stimulation.RésuméObjectifLa suppression de la réponse à un stimulus par les anesthésiques peut être considérée comme la sommation de la suppression de l’activité basale (pré-stimulus) et de la capacité de réponse (augmentée par le stimulus). La suppression par l’anesthésie de chacune de ces composantes au niveau du cerveau ainsi que des variables cardiovasculaires a été comparée chez le chat pour l’halothane, l’isoflurane et le sevoflurane.MéthodesTrente chats ont été répartis en 3 groupes (n = 10) selon l’agent anesthésique administré. Après avoir maintenu la concentration en fin d’expiration de l’agent anesthésique à 1,3 et 2,0 CAM pour 30 minutes, on a stimulé le nerf sciatique. Avant et après cette stimulation, on a enregistré l’électroencéphalogramme cortical (EEG), l’activité plurisynaptique de la formation réticulée mésencéphalique (R-MVA), la pression artérielle moyenne (PAM) et la fréquence cardiaque (FC).RésultatsLes tracés d’EEG et de R-MVA indiquent une plus grande dépression de l’activité cérébrale avant stimulation par l’isoflurane (31 ± 4% des valeurs d’éveils à 1,3 CAM, moyenne ± écart type moyen) et le sevoflurane (38 ± 5%) que par l’halothane (61 ± 5%,P< 0,05). À la suite de stimulation, la R-MVA ne montrait pas de différence entre les agents. Avant stimulation, la PAM et la FC des différents groupes n’affichaient aucune différence, mais après stimulation les valeurs de PAM étaient plus élevées dans le groupe sevoflurane (137 ± 9 et 103 ± 9 mmHg à 1,3 et 2,0 CAM) que dans le groupe halothane (103 ± 5 et 76 ± 3 mmHg,P< 0,05).ConclusionPour une même CAM, l’isoflurane et le sevoflurane ont une action suppressive plus intense sur l’activité de base du SNC que l’halothane; d’autre part, ces deux agents ont une action suppressive faible de la réponse à une stimulation périphérique.

Airway obstruction by a transesophageal echocardiography probe in an adult patient with a dissecting aneurysm of the ascending aorta and arch

Abstract TRANSESOPHAGEAL ECHOCARDIOGRAPHY (TEE) is now widely used not only in cardiac surgery, but also in noncardiac surgery when the patient has cardiovascular disease. TEE provides useful information not previously available during operations. Although it is generally a safe procedure, complications have been reported. 1 Airway obstruction is a serious complication but, to these authors’ knowledge, it has been reported only in children. 2,3 A case of airway obstruction caused by a TEE probe in an adult undergoing thoracic aortic aneurysm repair is reported.

Anticonvulsant effects of sevoflurane on amygdaloid kindling and bicuculline-induced seizures in cats: comparison with isoflurane and halothane

AbstractPurpose. We compared the anticonvulsant effects of sevoflurane with those of isoflurane and halothane in amygdaloid kindling and bicuculline-induced seizures in cats. Methods. In a crossover design, the effects of 70% nitrous oxide, and 0.3, 0.6, and 1.5 minimum alveolar concentration (MAC) of volatile anesthetics were studied in five cats in which the amygdala was electrically stimulated at the current used for establishing the kindled state. The effects of 0.6 and 1.5 MAC of volatile anesthetics were studied in another five cats, in which 0.2 mg·kg−1 of bicuculline was administered IV. Results. In the amygdaloid kindling model, all four anesthetics decreased the duration of after-discharge (AD), the rise of multiunit activity in midbrain reticular formation (R-MUA), and the behavior scores compared with findings without anesthetics. Halothane, at 1.5 MAC, significantly decreased the number of cats showing AD (P < 0.05). In the bicuculline-induced seizure model, all five cats showed repetitive spikes during 1.5 MAC of sevoflurane, whereas only two and three cats, respectively, showed the repetitive spikes during 1.5 MAC of isoflurane and halothane. All three volatile anesthetics decreased the rise of R-MUA, the duration of the repetitive spikes, and the behavior scores. The suppression of the rise in R-MUA and the behavior scores with 1.5 MAC of sevoflurane was significantly less than that with 1.5 MAC of isoflurane. Conclusion. The anticonvulsant effects of sevoflurane were less potent than those of halothane in the amygdaloid kindling model and less potent than those of isoflurane in the bicuculline-induced seizure model.

Insertion of a Fogarty Catheter through an Endotracheal Tube for One-lung Ventilation: A New Method

associated with this method is that the blocker may easily be dislodged when the connector is detached from the endotracheal tube (e.g. ,t o insert a suction catheter into the trachea) or when a fiberscope is inserted into or removed from the endotracheal tube alongside the catheter to confirm the blocker position. We report a simple method to minimize this problem. A 1-month-old boy with congenital cystic adenomatoid malformation of the left lung was scheduled for left upper lobectomy. Chest radiography showed that the mediastinum was markedly shifted to the right. We planned to block the left bronchus after induction of anesthesia, but before injection of a muscle relaxant, to minimize further expansion of the left lung. In the operating room, anesthesia was induced by inhalation of an increasing concentration of sevoflurane in oxygen. A small hole was made to the side of an endotracheal tube (3.5 mm ID) close to the tube connector. An 18-gauge needle was used to pierce the tube, and the needle was rotated to make a round hole. Resulting debris was removed. A 3-French Fogarty catheter, with its tip curved, was passed through the hole into the tube (fig. 1), and integrity of the cuff of the catheter was confirmed. The combination was inserted into the trachea using a laryngoscope, and adequate ventilation was confirmed. A fiberoptic bronchoscope was inserted into the endotracheal tube (via a self-sealing connector), and the Fogarty catheter was advanced easily into the left bronchus during fiberoptic view. The fiberscope was removed, and a transparent drape was used to cover the endotracheal tube hole through which the Fogarty catheter entered. After adequate one-lung ventilation was confirmed, vecuronium was injected. Throughout the operation, which was performed without complication, the Fogarty catheter was not dislodged, and there was no gas leak around the tube hole. Because the Fogarty catheter was inserted through a hole made to the side of the endotracheal tube (fig. 1), there was little risk of dislodgment of the Fogarty catheter during detachment or attachment of the right-angle connector or during insertion of the fiberscope into and its removal from the endotracheal tube. It was easy to affix the catheter to the endotracheal tube using adhesive tape. Although the manufacturer may not accept liability for a modified device, we believe that this method is clinically useful.