Yoshiro Sakaguchi

Effects of Various Antiepileptics Used to Alleviate Neuropathic Pain on Compound Action Potential in Frog Sciatic Nerves: Comparison with Those of Local Anesthetics

Antiepileptics used for treating neuropathic pain have various actions including voltage-gated Na+ and Ca2+ channels, glutamate-receptor inhibition, and GABAA-receptor activation, while local anesthetics are also used to alleviate the pain. It has not been fully examined yet how nerve conduction inhibitions by local anesthetics differ in extent from those by antiepileptics. Fast-conducting compound action potentials (CAPs) were recorded from frog sciatic nerve fibers by using the air-gap method. Antiepileptics (lamotrigine and carbamazepine) concentration dependently reduced the peak amplitude of the CAP (IC50 = 0.44 and 0.50 mM, resp.). Carbamazepine analog oxcarbazepine exhibited an inhibition smaller than that of carbamazepine. Antiepileptic phenytoin (0.1 mM) reduced CAP amplitude by 15%. On the other hand, other antiepileptics (gabapentin, sodium valproate, and topiramate) at 10 mM had no effect on CAPs. The CAPs were inhibited by local anesthetic levobupivacaine (IC50 = 0.23 mM). These results indicate that there is a difference in the extent of nerve conduction inhibition among antiepileptics and that some antiepileptics inhibit nerve conduction with an efficacy similar to that of levobupivacaine or to those of other local anesthetics (lidocaine, ropivacaine, and cocaine) as reported previously. This may serve to know a contribution of nerve conduction inhibition in the antinociception by antiepileptics.

Absence of anti-trifluoroacetate antibody after halothane anaesthesia in patients exhibiting no or mild liver damage.

It has been shown that the circulating antibodies, which bind to rat hepatic microsomal proteins obtained after in vivo exposure to halothane, are detectable by immunoblotting in patients with “halothane hepatitis (HH),” and that rabbit immunized anti-sera against trifluoroacetylated rabbit serum albumin (TFA-RSA) recognizes rat microsomal distorted polypeptides in almost the same way as do sera from patients with HH. In this paper, we report first the development of a novel method of synthesizing TFA-RSA using p-nitrophenyl TFA, and second the results of tests for circulating anti-TFA antibodies in the serum of 86 patients who had received halothane anaesthesia and developed no (67 patients) or mild (19 patients, the maximum activity of serum alanine aminotransaminase 519 IU · L−1) liver damage. Serum was selected from stored sera of post-transfusion patients. The new method of synthesizing TFA-RSA was convenient and was able to be done at neutral pH. Rabbit sera obtained after immunization with the newly synthesized TFA-RSA recognized the same polypeptides (109 kDa, 92 kDa, 80 kDa, 76 kDa, 64 kDa and 59 kDa) as the established anti-sera against TFA-RSA, and these reactions were inhibited in the presence of TFA-lysine. Circulating antibodies were not detected in our patients who had developed no or mild liver damage. The present finding supports the hypothesis that the appearance of circulating antibodies against microsomal distorted proteins are specific to patients with HH. Furthermore, we have shown here that the halothane-induced mild increase in ALT activity is not associated with the appearance of those circulating antibodies, supporting the pathophysiological difference between HH and halothane-induced mild hepatic damage.RésuméOn a montré que les anticorps circulants qui se lieńt au protéines microsomiques hépatiques du rat après une exposition in vivo à l’halothane peuvent être détectés par immunotransfert chez les patients atteints d’« hépatite à l’halothane (HH) ». On a montré aussi que les anti-sérums de lapins immunisés contre l’albumine sérique trifluoroacétylée (TFA-RSA) reconnaissaient les polypeptides microsomaux déformés de rat de façon presque identique au serums de patients atteints d’HH. Dans cet article, nous rapportons d’abord le développement d’une nouvelle technique de synthèse de TFA-RSA à partir du p-nitrophényl TFA, et deuxièmement le résultat d’épreuves de détection des anticorps anti-TFA dans le sérum de 86 patients qui ont été anesthésiés à l’halothane et n’ont pas présenté (67 patients) ou ont présenté une lésion hépatique légère (19 patients dont l’activité de l’analine aminotransaminase n’a pas dépassé 519 UI · L−1). Le sérum a été choisi parmí des sérums stockés après transfusions. La nouvelle méthode de synthèse de la TFA-RSA est pratique et réalisable avec un pH neutre. Les sérum de lapins obtenus après immunisation avec la nouvelle TFA-RSA de synthèse ont reconnu les mêmes polypeptides (109 kDa, 92 kDa, 80 kDa, 76 kDa, 64 kDa et 59 kDa) que les anti-sérum TFA-RSA éprouvés, et ces réactions ont été inhibées en présence de TFA-lysine. Les anticorps circulants n’ont pas été décelés chez nos patients sans atteinte ou avec légère atteinte hépatique. Ces données supporte l’hypothèse selon laquelle l’apparition d’anticorps circulants contre les protéines microsomi-ques déformées sont spécifiques aux patients atteints de HH. Nous avons montré de plus, que la légère augmentation de l’activité de l’ALT n’est pas associée avec l’apparition de ces anticorps circulants, ce qui supporte la différence physiopathologique entre l’HH et la lésion hépatique légère induite par l’halothane.

A possible increase in plasma norepinephrine by removal of the liver

Background: It has recently been suggested that the human liver plays an important role in clearing plasma norepinephrine, especially in restricting most of the norepinephrine to reach the systemic circulation from the gut.

Retrospective study of post-anesthetic mild liver disorder associated with inhalation anesthetics, halothane and enflurane.

The incidence of post-anesthetic mild liver disorder (PAMLD) was compared between 928 patients administered halothane and 1,766 patients administered enflurane. They were selected from 19,504 surgical patients administered general anesthesia at Kyushu University Hospital over the past 6 years and 4 months. They had had normal liver function before operation and had no history of blood transfusion. Alanine aminotransferase (ALT) levels exceeding 70 IU·l−1 within 180 days after operation were found in 226 patients in the halothane group (24.4%), and in 250 patients in the enflurane group (14.2%) (P<0.01). Both maximum ALT levels and duration of ALT elevation were higher and longer in the halothane group (P<0.01). These results suggest that, not only in the development of fulminant hepatitis but also in PAMLD, enflurane is less hepatotoxic than halothane.

USEFULNESS OF EPIDURALLY EVOKED CORTICAL POTENTIAL MONITORING DURING CERVICOMEDULLARY GLIOMA SURGERY

This report describes a patient with an intramedullary ependymoma at the region of the cervicomedullary junction in whom there was an abolition of somatosensory evoked potentials following median nerve stimulation. During intraoperative monitoring of cortical potentials elicited by epidural cervical cord stimulation, the tumor was removed. Posterior epidural stimulation appeared to depolarize more ascending fibers than did stimulation of a single peripheral nerve. We recommend that, in cases of operations in this vital area, epidurally evoked cortical potentials be monitored intraoperatively.

Whole body oxygen consumption during extracorporeal hepatic resection: usefulness of continuous monitoring of mixed venous oxygen saturation.

Whole body oxygen consumption was measured using a thermodilution fibreoptic catheter in two patients undergoing extracorporeal hepatic resection. Each patient had virtually normal liver function before the operation. Anaesthesia was induced and maintained in a standard fashion and a venovenous bypass instituted. The anhepatic periods were 302 and 157 min. Upon removal of the liver, the oxygen consumption decreased by about 40% (50 mL/min), while the mixed venous oxygen saturation increased by about 15%. Following re‐implantation, the oxygen consumption recovered and increased transiently above control values, while the mixed venous oxygen saturation changed in a reciprocal way. Monitoring whole body oxygen consumption instead of hepatic oxygen consumption seemed helpful in estimating restoration of blood flow and functions in the liver after reperfusion. It was also suggested that changes in oxygen consumption as well as those in cardiac output and haemoglobin concentration could be predicted easily by continuous monitoring of mixed venous oxygen saturation during the peri‐anhepatic period.

Unexpected resistance to pancuronium in a patient with myotonic dystrophy (myotonia dystrophica).

baldness, and cataract formation. In addition, he appeared to have cardiac dysrhythmias associated with myotonia dystrophica, and he was diagnosed 7 years previously with Adam-Stokes’ syndrome. However, without any cardiac medication, first-degree atrioventricular block (PQ interval, 0.28s) was the only abnormality found in the resting electrocardiogram, and the echocardiogram was normal. Pulmonary function tests, chest X-rays, and arterial blood gas analysis were all within normal limits (NL). The patient’s serum concentrations of electrolytes were all normal. However, the preoperative screening tests on the endocrine system revealed the presence of mild adrenocortical insufficiency due to pituitary dysfunction: urine 17hydroxycorticosteroids, 0.85 to 2.465 (NL 5 3.6–9.0) mg·day21; 17-ketosteroids, 1.68 to 4.35 (NL 5 3.0–13.0) mg·day21; serum cortisol 6.2 (NL 5 5.5–17.0) μg·dl21; serum ACTH 13 (NL 5 30–60) pg·ml21; ACTH test, within NL. Thyroid function was, however, normal. The preoperative laboratory tests also indicated the presence of hyperlipidemia (triglycerides, 241–384mg·dl21; cholesterol, 255–286mg·dl21). Other laboratory data, including those on both hepatic and renal function, were normal. The patient had not previously undergone surgery with general anesthesia. The patient was premedicated with intramuscular hydroxyzine hydrochloride (50mg) and atropine sulfate (0.5mg) 45min prior to the induction of anesthesia. Because of the adrenocortical insufficiency, 100mg of hydrocortisone was intravenously administered immediately before induction of anesthesia. The patient was then mildly sedated with intravenous diazepam (5mg) and fentanyl (150μg), and the trachea was successfully intubated without using a neuromuscular blocking agent while the patient was sedated and awake. After endotracheal intubation, the lungs were easily ventilated, and anesthesia was subsequently maintained with 67% N2O/1–3% enflurane in oxygen and supplemented by further intravenous administration of fentanyl (total

Rationale for preoperative screening of anti-HCV antibody

We investigated the incidence of the anti-HCV antibody and associated factors in 1,031 surgical patients who had received blood transfusion during or after operation from October 1988 to April 1991, at Kyushu University Hospital.One hundred fifteen patients (11.2%) were anti-HCV positive. Sixty of the 219 patients (27.4%) with a history of transfusion were positive, as were 55 of 812 (6.8%) without it. Patients aged under 40 showed a 0.6% positive rate (1 of 175) as did 8.5% (54 of 637) of those 40 and over in the no transfusion history group. Among the 637 patients without transfusion histories and aged over 40, patients with preoperative maximum ALT value over 36 IU·l−1 had significantly higher positivity (16.0%, 29/181) than those with ALT values less than 35 IU·l−1 (5.5%, 25/456,P<0.01).The incidence of anti-HCV antibody in preoperative surgical patients in our hospital is ten times higher than that of donors. Anti-HCV are associated with transfusion, age, and liver dysfunction. Operating room personnel are at high risk because of contact with many HCV carrier patients.

Analysis of intra-operative blood transfusions at Kyushu University Hospital during the last four months.

To understand the strategy of anesthesiologists regarding intra-operative transfusion, we analyzed cases at Kyushu University Hospital. During the last four months, intra-operative blood transfusions were performed in 172 out of 1, 525 (11.3%) surgical operations done in our operating room. Among these 172 cases, as many as 30% (55 cases) were managed by autologous transfusions, either preoperative deposition or intra-operative cell saving. For red cell transfusion, red cell concentrates derived from 400ml of donated blood were used in most cases (224/236, 95%). The critical hematocrit level at which anesthesiologists introduced blood transfusion was 25%, instead of 30%, the generally accepted level. All platelet transfusions were done with platelet concentrates obtained by single donor apheresis. These results indicate that adverse reactions of homologous blood transfusions such as post-transfusion hepatitis or post-transfusion graft-versus-host disease are well understood by anesthesiologists, and efforts to reduce transfused blood units were made. Only 15% of all transfused blood units were of fresh frozen plasma. This means that anesthesiologists recognized that fresh frozen plasma should be used to supplement coagulation factors. However, one of the problems to be settled is the overuse of albumin solutions. In the present series, 5% albumin solutions were administered in over 60% of transfused cases to maintain colloid osmotic pressure, but many cases could have been managed by alternative measures.