Published papers

We tested the hypothesis that the type of fluid infused to chronically maintain intravascular volumes would modify both microvascular integrity and cellular structure in extrapulmonary organs in hyperdynamic sepsis. After cecal ligation and perforation, awake sheep were treated for 48 h with 10% pentastarch (n = 9), 10% pentafraction (Du Pont Critical Care; n = 8), or Ringer lactate (n = 8) titrated to maintain a constant left atrial pressure. After 48 h of fluid therapy, biopsy samples were taken from the left ventricle and gastrocnemius for electron microscopy. At this time, all groups demonstrated a similar hyperdynamic circulatory response, increased systemic O2 utilization and organ blood flows, measured by radioactive microsphere injection. However, greater capillary luminal areas with less endothelial swelling and less parenchymal injury were found in septic sheep treated with pentastarch vs. Ringer lactate infusion in both muscle types. Pentafraction showed few benefits in study end points over pentastarch. Thus, we conclude that chronic intravascular volume resuscitation of hyperdynamic sepsis with pentastarch ameliorated the progression of both microvascular and parenchymal injury. These findings indicate that microvascular surface area for tissue O2 exchange in sepsis may be better preserved with chronically infused colloid, resulting in less parenchymal injury.

Since the original technique using the Bullard laryngoscope requires considerable practice to be reliable, we have developed an easier method with a directional-tip endotracheal tube through the nostril. We first examined the feasibility of our method in patients with or without difficult airways. All 26 patients with difficult airways were successfully tracheally intubated with our method, and times for visualization and intubation were not different from those in 10 patients with normal airways. We further examined the direction of the tips of endotracheal tubes through the nostril in 128 patients with normal airways using four combinations of two kinds of both laryngoscopes (Bullard and Macintosh) and endotracheal tubes (directional- tip tube: Endotrol(TM), Mallinckrodt Laboratories, Athlone, Ireland; or straight distal-end tube: Blue Line(TM), Portex Ltd., Hythe Kent, United Kingdom). We found that a combination of the Bullard laryngoscope and the Endotrol(TM) tube had a higher probability of accessing the center of the glottis than the others. In conclusion, nasal insertion of a directional-tip tube assisted by the Bullard laryngoscope is an assured and prompt procedure for intubating the tracheas of patients with difficult airways.

This study was done to clarify whether end-tidal carbon dioxide (ETCO2) concentration is an effective monitor as an indicator of survival and prognosis of patients who arrived with cardiac arrest. We measured ETCO2 concentration in 30 patients with pre-hospital cardiac arrest during cardiopulmonary resuscitation (CPR). Six patients were resuscitated successfully and the others were not. The values of ETCO2 of the resuscitated patients, at the time of starting advanced life support were varied from 0 to 4.5% (mean 1.4%), which were not different from the values in patients who were not resuscitated (mean 0.87%). In 13 patients who were not resuscitated, the initial values of ETCO2 during CPR were below 1.0%, whereas the other 11 patients showed high ETCO2 values (above 2.5%), which were dependent on the degree of chest compression. This suggests that ETCO2 monitoring during cardiopulmonary resuscitation is a good non-invasive indicator to evaluate the efficacy of chest compression itself, but its initial values during CPR are not correlated with success of resuscitation in patients with pre-hospital cardiac arrest.

We measured plasma endothelin (ET) in 11 patients undergoing cardiac valve replacement under high dose fentanyl (116.6 ± 15.4 μg · kg-1, mean ± SD) anesthesia. Arterial blood samples were obtained: 1) before induction of anesthesia (control), 2) just before the start of cardiopulmonary bypass (CPB), and 3) just before the end of CPB. Endothelin levels were analyzed by radioimmunoassay based on double antibody method using Silica ODS suspension. ET concentrations in period 1, 2, and 3 were 3.0 ± 1.1, 4.2 ± 1.7 and 4.5 ± 1.8 pg · ml-1 (mean ± SD), respectively. There were no significant differences among these three values (P < 0.05). The results suggest that under high dose fentanyl anesthesia, surgical stress including that of CPB might not affect ET concentration in plasma.

To determined the clinical relevance of the sympathetic response to out-of-hospital cardiac arrest, we measured plasma concentrations of catecholamine and cortisol in ten such arrested patients on their arrival. The duration of cardiac arrest was estimated from 9 to 200 min before basic life support was initiated by ambulance personnel. Two of the patients developed spontaneous pulses in response to ALS and were resuscitated, and the others were not, although the length and the extent of ALS were not different between the groups. Plasma concentrations of epinephrine (EN), norepinephrine (NE) and cortisol prior to ALS in both groups were markedly elevated. In particullar, the patients who never regained spontaneous pulses showed 58-fold and 12-fold increase in the plasma EN and NE levels, respectively, which were much higher than those in the resuscitated cases; 8- and 1.7-fold increase, respectively. These massive EN and NE discharges correlated well with the arrest time (r = 0.96 and 0.94, respectively) and the degree of acidosis (r = -0.82 and -0.82, respectively). © 1991.

Halothane was administered in oxygen to a young man in status asthmaticus whose bronchospasm did not respond to usual treatments. Plasma catecholamine concentrations were measured during and after bronchospasm. Fifteen minute inhalation of halothane produced marked bronchodilatation as reflected in decreased peak airway pressure, decreased wheezing and fall in PaCo2 from 110 mmHg to 45 mmHg. Treatment with halothane was discontinued after 120 min inhalation. Arterial blood samples were obtained to determine free and total catecholamine (CA) on the following four occasions: 1. during status asthmaticus, 2. fifteen minutes after inhalation of halothane, 3. one day after bronchospasm and 4. two days after bronchospasm. During attack, free norepinephrine and epinephrine concentrations were markedly elevated. These values decreased remarkably after administration of halothane. Total norepinephrine and epinephrine were also elevated during bronchoconstriction, and these high concentrations persisted after bronchodilatation. The changes in CA els suggest that sympathoadrenal hyperactivity elicited by acute asthma can be suppressed by halothane as evidenced by the decreased concentration in free catecholamines, which are physiologically active. The levels in total catecholamine did not correlate with the patient's condition. Therefore, judgement based only on the levels in total CA might lead to misinterpretation in estimating sympathoadrenal activity.

Inhibitory effects of diazepam and flunitrazepam on the superoxide anion (O2-) -generating system in granulocytes were examined for their clinical relevance. When the effects of commercial solutions and pure preparations were compared using porcine and human polymorphonuclear leucocytes in vitro, the solutions were found to be more inhibitory than the pure drugs by 4-11 times, indicating that inhibition was caused mainly by the additives in the solutions. Concentrations of the additives required for 50% maximal inhibition of the system were 2.3, 7.5 and 0.9 μl ml-1 for propylene glycol, ethanol and benzyl alcohol, respectively, while those of pure diazepam and flunitrazepam were 220 and 190 μg ml-1, respectively, under comparable conditions. However, plasma concentrations of the benzodiazepines and their additives during clinical use were far less than these inhibitory concentrations, indicating that they had no appreciable effect on the O2--generating system in polymorphonuclear leucocytes of patients. © 1991 British Journal of Anaesthesia.

Transurethral resection of urinary bladder tumor was performed under spinal anesthesia which has been considered to be rather contraindicated in a patient with idiopathic hypertrophic cardiomyopathy. Caution was exercised not to compromis myocardial oxygen supply demand ratio. Central venous pressure (CVP) was continuously monitored and crystalloid solution was infused to maintain CVP in pre-anesthetic level, thereby preventing the reduction in arterial pressure. The patient was hemodynamically stable throughout the operation. This case indicates that if adequate preload could be preserved and hypotension avoided, spinal anesthesia may not be precluded in patients with idiopathic hypertrophic cardiomyopathy.

This study was undertaken to determine whether midazolam alleviates sympathoadrenal response evoked by tracheal intubation in elderly patients with hypertension. Anesthesia was induced with midazolam in a sleep dose followed by vecuronium 0.1 mg · kg-1. Heart rate and blood pressure were recorded before, 1 and 3 minutes after induction with intubation. Free and total catecholamine (CA) in plasma were measured at each time. Dopamine, norepinephrine and epinephrine (EN) were determined using fluorescens derivatization with diphenylethylenediamine by HPLC. Although heart rate and diastolic pressure rose in some degree 1 min after intubation, free and total CA concentrations did not increase during study period. Free and total EN levels decreased significantly 3 min after intubation. The absence of elevation in plasma CA concentrations, especially in free CA, which is physiologically active, would contribute to produce circulatory stability on laryngoscopy and tracheal intubation. However, the mystery of why hyperdynamic state was produced without the increase in CA concentrations remains to be solved, even though it occurred for a short period of time.

Presented here is a case of unilateral pulmonary edema following acute subglottic edema after removal of an endotracheal tube. A 3-year-old boy, diagnosed as having nondiphtheric croup and pectus excavatum deformity, was scheduled for repair of a cleft lip. No complication occurred during the operation. After removal of the endotracheal tube, he showed dyspnea and cyanosis and was later found to have acute subglottic edema. After reintubation of the trachea, frothy pink fluid was discharged from the tube, and chest roentgenogram showed a right-sided alveolar infiltrate. Many factors may cause unilateral pulmonary edema, but it is suggested that acute subglottic edema and unilateral bronchial fragility strongly affected this episode. © 1990.

Propylene glycol, ethanol and benzyl alcohol are usually included in the injection solutions of diazepam, flunitrazepam and others as solvents and/or pain relief agents. It was reported that diazepam and flunitrazepam inhibited oxidative burst of human neutrophils to produce O2-, H2O2 and other active oxygen species. However, the present study revealed that the solvents had far more potent inhibitory effects in this regard than diazepam and flunitrazepam themselves. The solvents reversibly inhibited phagocytosis and O2- production by neutrophils, and they were stimulated by both soluble stimulants, phorbol myristate acetate or laurate, and a particulate stimulant, serum opsonized zymosan, in a dose-dependent manner. Benzyl alcohol, which had the most potent effect among the solvents, appeared to inhibit the O2- generating enzyme NADPH oxidase directly, rather than by affecting intracellular calcium mobilization. Thus one should keep in mind such unexpected effects of the solvents included in solutions for injection.

We have compared the effects of sevoflurane and halothane on serum myoglobin (Mb) and creatine phosphokinase (CPK) in anesthetized children. The subjects of the study were children (ASA physical status I, 2 years 11 months to 11 years of age) scheduled for minor surgical procedure under general anesthesia. They were divided into three groups; two groups were injected with 1 mg/kg of succinylcholine chloride (SCC) to facilitate tracheal intubation and maintained with sevoflurane, nitrous oxide and oxygen (Group SS, n = 10), or maintained with halothane, nitrous oxide and oxygen (Group SH, n = 12), and the last group was injected with 0.1 mg/kg of pancuronium bromide and maintained with halothane, nitrous oxide and oxygen (Group PH, n = 10). Blood samples were drawn before and 5, 20, 60 min after the injection of the muscle relaxants. Serum myoglobin value was analyzed by the antibody radioimmunoassay technique. While the Mb value increased markedly in the two SCC injected groups, the increase was significantly less in the Group SS (60 min value 454 ± 306 ng/ml) than in the group SH (2192 ± 2217 ng/ml), and the magnitude of the increase in the Group SS was one fifth of the latter group. The CPK value increased only in the Group SH to 174.1 ± 114.1 IU/l at 60 min. In the Group PH, neither Mb nor CPK values increased. These results indicate that the release of Mb and CPK from the muscle cells into the blood during sevoflurane anesthesia is less than that of halothane. The results suggest that sevoflurane offers an advantage for anesthesia of children.

A new volatile anesthetic, sevoflurane, was evaluated concerning its rapid induction and recovery, a result of its low blood/gas partition coefficient (0.60). Sevoflurane was administered to 50 healthy children with ages between 5 months and 11 years undergoing herniorrhaphy. The time intervals for onset of sleep, induction and recovery (107, 201, 306 seconds, respectively) were not so rapid. But the induction with sevoflurane was smooth because older children reacted little to the older of sevoflurane. In addition, the condition after recovery was calm with clear consciousness, and there was a low incidence of postoperative vomiting and fever. Therefore, sevoflurane may prove suitable for use in pediatric anesthesia.

Bronchography is required in infants suffering from respiratory distress due to tracheobronchial abnormalities or pulmonary and/or cardiovascular disease. In 10 infants with ages below 1 year and 2 months bronchography was performed under halothane-oxygen anesthesia with spontaneous respiration. We measured arterial blood gases after each of the following procedures: endotracheal intubation, instillation of contrast medium, instillation of 0.5 ml/kg of saline for tracheobronchial toilet, tracheobronchial toilet and finally extubation. During the whole procedure, PaO2 ranged from 78 to 406 mmHg. PaCO2 32~95 mmHg and pH 7.05~7.42. These data may be the result of increased intrapulmonary shunt due to age, general anesthesia and high oxygen concentration. Despite decreased PaO2 or elevated PaCO2, no obvious or severe cardiac complications were observed, and after the procedure the patients' courses were uneventful. However, we believe that bronchography should be performed with caution in infants with congestive heart failure or anemia.

In 8 patients with moderate hypertension, aged between 59 and 73 years, we measured excretion of norepinephrine (NE) and epinephrine (EN) per 1 mg of urine creatinine in order to evaluate the sympathetic activity during either gastrectomy or cholecystectomy. Catecholamines were analysed by high-performance liquid chromatography using a native fluorescence detector. During the surgery, we observed no significant increase in NE and EN excretion. The results suggest that this anesthetic procedure can suppress the intra-operative rise in sympathoadrenal activity.

In 10 patients with ages ranging between 23 and 37 undergoing elective gynecological laparoscopy under pethidine-N2O-pancuronium anesthesia, we measured excretion of norepinephrine (NE) and epinephrine (EN) per 1 mg of urine creatinine in order to evaluate the sympathetic effect of this surgical procedure. Catecholamines were analysed by high-performance liquid chromatography using native fluorescence technique. During laparoscopy, we observed a significant increase in NE and EN excretion (from 73 ± 32 ng/mg·cr to 151 ± 89 ng/mg·Cr and from 24 ± 16 ng/mg·Cr to 39 ± 22 ng/mg·Cr, respectively, mean ± SD). Such increases are considered to be beneficial in maintaining arterial pressure in these cases, where considerable reduction in cardiac output caused by high intraabdominal pressure is expected.