[Awake pronation of surgical patients with cervical spinal lesions].

Positioning of patients with cervical spinal lesions under general anesthesia may lead to serious neurological complications. The authors attempted awake pronation in eighteen patients to minimize the risks. In all patients, cervical instability or cervical spinal cord compression was diagnosed, and posterior fusion or laminoplasty under general anesthesia was planned. Naso-tracheal intubation was performed by broncho-fiberoptic scope under topical anesthesia and light sedation. After tracheal intubation, pronation was completed while patients were still awake. Twelve patients could change their position almost by themselves, and needed only a little assistance of the medical staff. After the patients settled in appropriate position, general anesthesia was induced. Neurological status was assessed before and after the intubation, and just before the induction of general anesthesia, to prove the absence of complications. Operations were accomplished without major troubles in all patients. During post anesthetic interviews, eight patients had memory of the positioning, but none of them had any complaints about the procedure. Awake pronation may be useful to minimize the risk of neurological complications related to positioning of surgical patients, and also need less assistance by medical staff.

[Epidural midazolam for treatment of postoperative pain].

Postoperative pain relief and sedation with epidural midazolam were studied. Twenty-one patients for elective upper abdominal surgery were divided into 3 groups. Epidural catheter was inserted into thoracic epidural space before induction of general anesthesia. In each group, either 10 ml saline only, midazolam 0.05 mg.kg-1 + 10 ml saline, or midazolam 0.1 mg.kg-1 + 10 ml saline was injected into epidural catheter for complaint of pain in recovery room. For 120 minutes after epidural injection, blood pressure, heart rate, respiratory rate, serum concentration of midazolam, and sedation score were monitored. In midazolam injected groups, only slight changes were seen in blood pressure, heart rate, and respiratory rate. Sedation score was graded from 1 to 6:1 means complete sleep, and not responded to verbal command, 6 means agitated and many complaints. Midazolam 0.1 mg.kg-1 + 10 ml saline group had the lowest score, and saline 10 ml group had the highest score. Prolonged sedation and pain relief were obtained in midazolam injected group, especially 0.1 mg.kg-1 + 10 ml saline group. Serum midazolam concentrations were lower than 200 ng.ml-1. These values were considered as the lower limit for sedation by intravenous administration. In conclusion, epidural midazolam was useful for postoperative pain relief. The mechanism is considered to involve spinally mediated CNS action or direct spinal action.

[A patient who recovered successfully from severe anemia which continued for one hour].

A 79-year-old woman had her cervical spinal cord injured and laminoplasty of the neck was performed. Uncontrollable venous bleeding was encountered during the operation and about 5000 ml of blood was lost in one hour. Massive infusion of 5% albumin and hydroxyethylstarch (HES) was done to maintain the intravascular volume. Therefore, her hematocrit value (Ht) decreased to 4.5%. Her rectal temperature went down to 34.5 degrees C. The operation was finished in haste. We studied leg pain experienced under spinal anesthesia in leprosy patients. Seven of twenty patients complained of the leg pain a few minutes after spinal block. The pain was localized in the parts of deafferentation or phantom limb, and was relatively mild and controllable. We consider that the inhibitory system is inactivated when the somatic impulse is blocked by spinal anesthesia, and as a result the abnormal burst activity of dorsal horn produced by peripheral nerve damage of leprosy causes phantom pain.

[Midazolam for rapid sequence induction].

We compared midazolam 0.2 mg.kg-1 and fentanyl 50 micrograms with thiamylal 4 mg.kg-1 for rapid sequence induction. We could use midazolam safely in patients with bronchial asthma or drug allergy. There was no difference in time from the beginning of induction to intubation between midazolam treated group and thiamylal treated group. Changes in systolic as well as diastolic blood pressure and heart rate during 2 hours from intubation were smaller in midazolam treated group than in thiamylal treated group. In midazolam treated group, no arrhythmias were observed at the time of intubation. We could reduce the amount of anesthetics in midazolam treated group during 2 hours from intubation. From the results mentioned above, we conclude that midazolam is a useful agent for rapid sequence induction.

[Myasthenia gravis is improved temporarily at postburn period].

A 62-year-old woman with a 25-year history of myasthenia gravis (MG) was admitted to our hospital due to burn injury over 20-25% of the total body surface area. Five months before admission, the serum concentration of acetylcholine receptor (AchR) antibodies was 80.9 nmol.l-1 (normal range < 0.3 nmol.l-1). Anticholinesterase agents had been administered for MG, but were discontinued six days after admission due to muscarinic side effects, but no symptoms of MG appeared. Thirteen days after admission, the AchR antibody titer was 21.2 nmol.l-1. Free skin grafting was performed under general anesthesia without any event. About 80 days after admission, weakness of extraocular muscles appeared. Positive tensilon test and the characteristic electromyographic findings revealed deterioration of MG, and anticholinesterase agents were resumed. Ten months after admission, the AchR antibody titer was 50.4 nmol.l-1. The mechanism of the temporary improvement of MG symptoms does not appear to be explained by the diffuse immunosuppression after burn. At a postburn period, nicotinic AchRs at the neuromuscular junction are known to be temporarily induced. This up-regulation may have caused the temporary improvement in this patient.

[Effects of inorganic fluoride, inhalation time and dosage of sevoflurane on renal function during sevoflurane anesthesia of long duration].

In sevoflurane anesthesia of long duration, we studied correlations with renal function of the area under the curve (AUC), rate of decrease and maximum level of serum inorganic fluoride (F), sevoflurane dosage, and duration of administration. In 15 neurosurgical patients, we measured serum and urine levels of F, blood urea nitrogen (BUN), creatinine, serum and urine beta 2-microglobulin (BMG), and urine N-acetyl-beta-D-glucosaminidase (NAG). AUC and the rate of decrease of serum F were calculated. There were no correlations among the maximum level, AUC, the rate of decrease of serum F, sevoflurane dosage, duration of administration, BUN, creatinine, BMG, and NAG. It is concluded that in sevoflurane anesthesia of long duration, F, sevoflurane dosage and duration of administration do not affect renal function.

[Anesthesia for a pregnant patient with ruptured cerebral arterio-venous malformation].

A 29 year old woman suffered sudden hemiplegia, vomiting and headache during the 28th week of her first pregnancy. She was diagnosed as the intracranial hemorrhage due to the ruptured arteriovenous malformation, and emergency operation was performed. Anesthesia was induced with crush induction using thiamylal, fentanyl, pancuronium and suxamethonium, and maintained with fentanyl, isoflurane and nitrous oxide in oxygen. During and after surgery, fetal heart rate and uterine contraction were monitored continuously. Intense hypotension was not chosen because it may place a fetus at risk of intrauterine asphyxia. Ventilation was controlled to maintain PaCO2 between 30 and 35 mmHg. During surgery, D-mannitol 60 g was infused slowly to prevent fetal dehydration, and after surgery no osmotic diuretics were used. Ritodrine hydrochloride, which prevented premature delivery, was continuously infused after surgery. Her neurological symptom was improved and her baby was delivered vaginally at 41st gestational week.

[Does induction with midazolam decrease stress response during anesthesia?].

The effects of midazolam on stress response during surgery compared with thiamylal were studied. Twelve patients were divided into 2 groups at random; midazolam group and thiamylal group. Anesthesia was induced with midazolam 0.2 mg.kg-1 or thiamylal 4 mg.kg-1 in each group, and maintained with O2 2 l.min-1, N2O 4 l.min-1 and enflurane. The plasma concentration of catecholamine was measured at preinduction, 10, 30, 60, 120 and 180 minutes after intubation. No significant differences were seen between 2 groups in plasma concentration of catecholamine. In midazolam group, plasma concentration of epinephrine decreased significantly 10 minutes after intubation as compared with preinduction level. The plasma concentration of norepinephrine in midazolam group tended to decrease. In thiamylal group, plasma concentration of norepinephrine tended to increase and increased significantly at 120 and 180 minutes after intubation as compared with preinduction level. These results suggest that induction with midazolam suppresses stress response during anesthetic induction and surgery more intensely than induction with thiamylal.

[Interaction of nicardipine and inhalational anesthetics--comparison between enflurane and isoflurane].

The effects of nicardipine 1 mg bolus injection under enflurane anesthesia were compared with those under isoflurane anesthesia. Twelve neurosurgical patients were divided into 2 groups, enflurane group (n = 6) and isoflurane group (n = 6). In all patients anesthesia was induced with midazolam, thiamylal, fentanyl and vecuronium. Anesthesia was maintained with fentanyl, nitrous oxide, pancuronium plus enflurane (enflurane group) or plus isoflurane (isoflurane group). After incision of dura mater, nicardipine 1 mg was given through forearm venous line. For about 30 minutes before and after nicardipine injection, concentration of inhalational anesthetics was kept constant and no drugs were given. Blood pressure (BP), heart rate (HR), rate pressure product (RPP), and serum concentrations of catecholamine and nicardipine were monitored for 30 minutes after nicardipine injection. In isoflurane group, BP decreased more and longer, and increases of HR and serum concentration of catecholamine continued longer compared with enflurane group. Elimination half life of nicardipine was shorter, area under the curve (AUC) was smaller and clearance of nicardipine was larger in isoflurane group than in enflurane group. It was concluded that isoflurane increased the effects of nicardipine, which were BP depression and reflex sympathetic stimulation, than enflurane and that metabolism and elimination of nicardipine were accelerated more by isoflurane than by enflurane.

[Epidural midazolam with bupivacaine--optimal dose for postoperative pain relief].

Optimal dose of epidural midazolam with bupivacaine for postoperative pain relief was investigated. Forty seven patients for upper abdominal surgery were divided into 5 groups. Each group had either 0.25% bupivacaine 6 ml (control group), 0.25% bupivacaine 6 ml + midazolam 0.025 mg.kg-1 (0.025 group), 0.05 mg.kg-1 (0.05 group), 0.075 mg.kg-1 (0.075 group), or 0.1 mg.kg-1 (0.1 group) administered epidurally for complaint of first postoperative pain. Blood pressure (BP), heart rate (HR), respiratory rate (RR) and sedation score (SS) were monitored for 120 minutes, and the time interval for next analgesics (TNA) was checked. In each group, BP fell down 10 minutes after injection, HR was unchanged, and RR (except for 0.1 group) decreased, compared with the preinjection level. There was no difference between control group and others in BP, HR and RR. But 3 cases in 0.075 group and 4 cases in 0.1 group needed chin lift with a pillow under the shoulder for slight airway obstruction. The most optimal SS was obtained in 0.05 group. TNA was significantly longer in 0.025 and 0.05 groups than in the control group. It was concluded that the optimal dose of epidural midazolam with 0.25% bupivacaine 6 ml was 0.05 mg.kg-1 for postoperative pain relief after an upper abdominal surgery.

[Epidural midazolam with saline--optimal dose for postoperative pain].

Optimal dose of epidural midazolam with saline for postoperative pain relief was investigated. Forty three patients for upper abdominal surgery were divided into 5 groups. Each group had either 10 ml saline only (saline group), 10 ml saline + midazolam 0.025 mg.kg-1 (0.025 group), 10 ml saline + midazolam 0.05 mg.kg-1 (0.05 group), 10 ml saline + midazolam 0.075 mg.kg-1 (0.075 group), or 10 ml saline + midazolam 0.1 mg.kg-1 (0.1 group) administered epidurally for complaint of postoperative pain. Blood pressure (BP), heart rate (HR), respiratory rate (RR) and sedation score (SS) were monitored for 120 minutes, and the time interval for next analgesics (TNA) was checked. In each group, BP was unchanged compared with preinjection level. HR changes were less in 0.05 and 0.1 group than in others. RR changes were less in 0.025 and 0.05 group than in others. Optimal SSs were obtained in 0.025 and 0.05 groups. In 0.075 and 0.1 groups, many patients fell into complete sleep (not responded to verbal command). TNA was about 2 hours in 0.025 and 0.05 groups, over 6 hours in 0.075 and 0.1 groups. Complete sleep was the cause of long TNA in 0.075 and 0.1 groups. It was concluded that optimal dose of epidural midazolam with saline 10 ml was 0.05 mg.kg-1 for postoperative pain relief after upper abdominal surgery.

[Epidural administration of midazolam with saline or bupivacaine for postoperative pain].

Postoperative pain relief and sedation with epidural midazolam-saline or midazolam-bupivacaine were studied in 46 patients after elective upper abdominal surgery. They were divided into 6 groups. In each group, 10 ml saline, 10 ml saline+midazolam 0.05 mg.kg-1, 10 ml saline+midazolam 0.1 mg.kg-1 (saline group), 0.25% bupivacaine 6 ml, 0.25% bupivacaine 6 ml + midazolam 0.05 mg.kg-1 or 0.25% bupivacaine 6 ml + midazolam 0.1 mg.kg-1 (bupivacaine group) was administered via epidural catheter for complaint of pain. For 120 minutes after epidural injection, blood pressure (BP), heart rate (HR), respiratory rate (RR), sedation score, and serum concentration of midazolam (conc midazolam) were evaluated. The time interval until next complaint of pain (pain relief time) was measured. In midazolam injected group, BP, HR, RR were not changed from preinjection value, but sufficient sedation was obtained and pain relief time was significantly prolonged compared with saline or bupivacaine injected group. Midazolam level was lower than that of sedation level. There were no significant differences between saline group and bupivacaine group, but the pain relief effect was slightly stronger in bupivacaine group. It is concluded that epidural saline - midazolam or 0.25% bupivacaine - midazolam is useful for postoperative pain relief after upper abdominal surgery.

[Induction of anesthesia with midazolam and thiamylal].

Midazolam has a slow onset of action, while thiamylal causes pain on injection and circulatory changes. To compensate for these drawbacks, the usefulness of a combination of midazolam and thiamylal in anesthesia induction was studied. The combination method was compared to the induction with single use of thiamylal in 40 patients (20 patients in each group). The combination of 0.2 mg.kg-1 of midazolam and 1.9 mg.kg-1 of thiamylal showed a shorter onset of action than the 4-5 mg.kg-1 of thiamylal. Pain on injection was observed in 5 cases of thiamylal group but in no cases of combination group. The changes in blood pressure, heart rate and rate pressure product were obviously smaller in combination group than in thiamylal group. Although the recovery time from anesthesia of combination group (13.2 minutes) was longer than that of thiamylal group (10.5 minutes), this was not clinically important. It is concluded that anesthesia induction with the combination of midazolam 0.2 mg.kg-1 and thiamylal 1.9 mg.kg-1 is more useful than that of thiamylal alone.

[Anesthetic management of a patient with adrenocorticotropic hormone (ACTH) deficiency].

A 73 year old woman with ACTH deficiency was admitted to our hospital for gastrectomy. She had taken corticosteroid for 3 years. The day before surgery, she took 25 mg of hydrocortisone per os. Hydrocortisone 100 mg was administered intravenously 30 minutes before surgery, during and after surgery, and on the next day after surgery. Serum concentrations of ACTH and cortisol were measured 1 hour after the first administration of hydrocortisone 100 mg, 2 hours after the second and 15 hours after the third administration. The ACTH concentration was always lower than the lowest limit of detection. Cortisol concentrations were 140.0, 180.0 and 14.5 micrograms.dl-1 at each measurement. Serum concentration of aldosterone after the induction of anesthesia was lower than the normal range. Her hemodynamics were very stable and electrolytes balance was not disturbed with corticosteroid treatment during and after surgery.

[Concentrations of haptoglobin and free hemoglobin in preserved whole blood].

In bank blood, red blood cells are destroyed and free hemoglobin increases during preservation. Concentrations of haptoglobin and free hemoglobin were measured in 73 packages of preserved whole blood which had been kept for various periods, 1 to 21 days. Those blood samples were divided into 7 groups depending on preserved period, 1 to 3, 4 to 6, 7 to 9 days, and so on. Total haptoglobin decreased to less than 100 mg.dl-1 in the blood preserved over 7 days. Total hemoglobin increased with the passage of preserved period. Free hemoglobin appeared in 40% or more of the blood preserved over 7 days and its concentration increased depending on preserved time. Free hemoglobin of 10 mg.dl-1 or more was detected in the blood preserved over 7 days. It is recommended that for massive blood transfusion the whole bank blood under 7 days of preservation should be used.

[Surgical stress stimulates release of polymorphonuclear leukocyte elastase from a segmented neutrophil].

The studies were performed to find out whether increased serum levels of polymorphonuclear leukocyte elastase (PMNE) depend on increase of segmented neutrophils or increase of PMNE release from a segmented neutrophil on 17 patients for various elective surgeries. Serum levels of PMNE, leukocyte count and leukogram were determined before incision (preoperation), as well as on the 1st, 3rd and 5th day after operation. Serum levels of PMNE, segmented cell count, stab cell count, stab cell-segmented cell ratio increased most on the 1st postoperative day and decreased thereafter. Leukocyte count showed no significant changes. Serum levels of PMNE correlated well with PMNE released from a segmented neutrophil, but not with leukocyte count or segmented cell count. It was concluded that increased serum levels of PMNE by surgical stress depend on the increased PMNE release from a segmented neutrophil but not on the increased segmented cell count.

[Pharmacokinetics of midazolam in patients with liver damage for hepatectomy].

Pharmacokinetics of midazolam in patients with liver damage for hepatectomy was compared to that in patients without liver injury for gastrectomy. Anesthesia was induced with midazolam 0.15 mg.kg-1 and fentanyl. Serum concentration of midazolam was measured at 30 minutes, 1, 2, 3, 4, 6 and 8 hours after midazolam injection. Serum midazolam levels were not significantly different between the two groups at any time. The elimination half-life of midazolam was about 3 times longer in hepatectomy group (24.2 hours) than in the group without liver injury (8.4 hours). Area under the curve of the serum midazolam concentration was larger in the group with liver damage than in the group without it. But distribution volume and clearance of midazolam were not different between the two groups probably because of more blood transfusion and bleeding in hepatectomy group. The recovery time from anesthesia in hepatectomy group was as long as that in the group without liver injury. The results suggest that in patients with liver damage for hepatectomy, the elimination of midazolam is prolonged but its effect is not.

Total intravenous anesthesia. Midazolam-fentanyl vs enflurane-nitrous oxide.

This study was done to compare the hemodynamics, serum catecholamine levels and postoperative analgesia in total intravenous anesthesia with inhalation anesthesia. Thirteen patients for elective upper abdominal surgery, aged from 40 to 75 years, were studied. In the total intravenous anesthesia group (TIVA group, 7 patients), anesthesia was induced with 0.3 mg.kg-1 midazolam and maintained with 0.68 mg.kg-1.hr-1 midazolam for 15 minutes followed by 0.125 mg.kg-1.hr-1. Fentanyl was also administered as necessary. In the inhalation anesthesia group (inhalation group, 6 patients), anesthesia was induced with 5 mg.kg-1 thiamylal and maintained with 0.5-2.0% enflurane and 66% nitrous oxide in oxygen. In the TIVA group, the blood pressure and heart rate were as stable as those in the inhalation group. The serum concentration of catecholamines in the TIVA group rose significantly 60 minutes after intubation, in particular, the serum epinephrine level was higher than in the inhalation group. The time for extubation, respiratory rate and PaCO2 were not different between the two groups. The postoperative analgesic duration in the TIVA group was significantly longer than that in the inhalation group. The elimination half-life of midazolam was 1.675 +/- 0.281 hours in the TIVA group. In this study, TIVA failed to suppress the elevation of serum catecholamine levels, but it achieved stable hemodynamics during upper abdominal surgery and enough postoperative analgesia without affecting the extubation time, the respiratory conditions and the elimination half-life of midazolam.

Effects of sevoflurane anaesthesia on renal function--duration of administration and area under the curve and rate of decrease of serum inorganic fluoride.

The renal effects of serum inorganic fluoride in sevoflurane anaesthesia were studied in 15 patients separated into two groups according to whether anaesthesia had lasted more than 7 h. Serum and urine fluoride and beta 2-microglobulin, blood urea nitrogen, and serum creatinine were measured during and after anaesthesia. The area under the curve of serum fluoride (AUC0-infinity) was significantly higher for longer anaesthesia (more than 7 h), but serum fluoride at the end of inhalation and the rate of decrease of serum fluoride were similar in both groups. Although urine beta 2-microglobulin increased above normal after anaesthesia, there were no significant differences between groups. Other indices of renal function remained normal. Sevoflurane dose, duration of administration, serum fluoride at the end of inhalation, area under the curve and rate of decrease of serum fluoride were compared against indices of renal function using Spearman's rank correlated index. The only significant correlation was serum fluoride at the end of inhalation with serum creatinine. The duration of sevoflurane administration and the area under the curve for serum fluoride did not affect renal function.

Use of nitric oxide-nucleophile adducts as biological sources of nitric oxide: effects on airway smooth muscle.

Nitric oxide (NO)-nucleophile adducts are compounds of the general structure [XN(O)NO]-, where X is a nucleophile residue, and they release NO spontaneously in aqueous solution. This study determined the effects of two NO-nucleophile adducts [diethylaminodiazen-1-ium-1,2-diolate (DEA-NO) and sperminediazen-1-ium-1,2-diolate (DEA-NO) and sperminediazen-1-ium-1,2-diolate (spermine-NO)] on isometric force and the cytosolic concentrations of cyclic GMP ([cGMP]1), cyclic AMP ([cAMP]i) and calcium in canine tracheal smooth muscle. The ratio of fura-2 emission fluorescence intensities with excitation at 340- and 380-nm wavelengths (F340/ F380) was used as an index of cytosolic [Ca+2] concentration. Both DEA-NO and spermine-NO caused a concentration-dependent and reversible decrease in force (EC50 of 0.13 +/- 0.02 microM and 4.1 +/- 0.3 microM, respectively) and F340/F380, a concentration-dependent increase in [cGMP]i and no change in [cAMP]i. There were no significant differences in the relationship between [cGMP]l and the percentage decrease in force or in the relationship between the percentage decrease in F340/ F380 and the percentage decrease in force between tissues relaxed with DEA-NO or spermine-NO. Oxyhemoglobin increased the EC50 for both DEA-NO (from 0.13 +/- 0.03 microM to 8.1 +/- 0.2 microM) and spermine-NO (from 3.9 +/- 0.3 microM to 81.6 +/- 6.4 microM) and completely scavenged NO released by 0.13 (EC50) and 1 (EC100)microM DEA-NO. These results suggest that both DEA-NO and spermine-NO generate NO extracellularly and relax airway smooth muscle in association with an increase in [cGMP]i and a decrease in cytosolic Ca+2 concentration. NO-nucleophile adducts may serve as vehicles for the controlled delivery of NO into biological systems and thus provide a useful tool by which the physiology of NO can be investigated.