Predictive performance of eleven pharmacokinetic models for propofol infusion in children for long-duration anaesthesia.

Background: Predictive performance of eleven published propofol pharmacokinetic models was evaluated for long-duration propofol infusion in children. Methods: Twenty-one aged three-11 yr ASA I-II patients were included. Anaesthesia was induced with propofol or sevoflurane, and maintained with propofol, remifentanil, and fentanyl. Propofol was continuously infused at rates of 4-14 mg kg - 1 h - 1 after an initial bolus of 1.5-2.0 mg kg - 1 . Venous blood samples were obtained every 30-60 min for five h and then every 60-120 min after five h from the start of propofol administration, and immediately after the end of propofol administration. Model performance was assessed with prediction error (PE) derivatives including divergence PE, median PE (MDPE), and median absolute PE (MDAPE) as time-related PE shift, measures for bias, and inaccuracy, respectively. Results: We collected 85 samples over 270 (130) (88-545), mean (SD) (range), min. The Short model for children, and the Schüttler general-purpose model had acceptable performance (-20%≤MDPE ≤ 20%, MDAPE ≤ 30%, -4% h - 1 ≤ divergence PE ≤ 4% h - 1 ). The Short model showed the best performance with the maximum predictive performance metric. Two models developed only using bolus dosing (Shangguan and Saint-Maurice models) and the Paedfusor of the remaining nine models had significant negative divergence PE (≤-6.1% h - 1 ). Conclusions: The Short model performed well during continuous infusion up to 545 min. This model might be preferable for target-controlled infusion for long-duration anaesthesia in children.

[Fukuronori (Gloiopeltis furcata) extract: 90-day dietary toxicity study in F344 rats].

Fukuronori extract (FE), which is mainly composed of polysaccharides, and is an extract of the seaweed Gloiopeltis furcata, is permitted for use as a food thickening agent by the Ministry of Health and Welfare, Japan. In order to study the subchronic toxicity of FE, F344 rats of both genders were administered FE at concentrations of 0% (basal diet, control group), 0.5%, 1.5% and 5.0% in basal powder diet for 90 days, and observation of general condition, recording of body weight and food consumption, examination of hematology and blood chemistry, measurement of organ weight, and pathological examination were performed. Food consumption tended to increase in both sexes given FE at 1.5% and 5.0% throughout most of the experimental period. This was, however, considered not to be a toxic effect because the differences in body weight were small. Total cholesterol and triglycerides in serum decreased significantly (p < 0.05) and not significantly, respectively, in males of the 5.0% group. These changes were considered to be related to the intake of FE, but the differences were slight and within physiological ranges. Hematological and pathological examination revealed neither any particular adverse effect nor any significant difference from the control. Hence, dietary intake of 5.0% of FE, 3,362 mg/kg/day for males and 3,594 mg/kg/day for females as mean daily intake, for 90 days was considered to be a no observable adverse effect level in rats.

[Intraoperative management of heart transplantation in Japan--report of two cases].

We experienced intraoperative anesthetic management of two cases of heart transplantation in Japan. Both patients were in the end stage of cardiac failure due to dilated cardiomyopathy. One patient had had implantation of left ventricular assist system, and another patient had had implantation of automated cardioveter defibrillator. Transesophageal echocardiography was useful for the monitoring of cardiac function during the operation. Anti-arrythmic therapy including heart pacing and protection of right heart failure are important for the circulatory management of heart transplantation. The anesthesiologist is needed not only for the management of respiration and circulation but also for the prevention of infection and control of the time schedule.

[Anesthetic management for implantation of implantable cardioverter-defibrillators].

Implantable cardioverter-defibrillators (ICDs) were implanted in 44 patients at the authors' institution. The anesthetic management was reviewed retrospectively. Ten of the 44 patients received the third generation ICD devices, while the rest received the fourth generation devices. For thirteen patients receiving the fourth generation devices, implantation was performed under local anesthesia with monitored care of anesthesiologists. Propofol was infused to achieve deep sedation during induced ventricular fibrillation and later cardioversion for testing the devices. Implantation was performed under general anesthesia with combination of fentanyl and volatile anesthetics for the remaining 31 patients. Patients who received ICDs under local anesthesia had significantly greater values of ejection fraction in preoperative examination than values in patients who received ICDs under general anesthesia. Operation time of the implantation under local anesthesia was significantly shorter than that under general anesthesia. Though infusion of propofol produced a moderate decrease of blood pressure in patients who received ICDs under local anesthesia, no patient showed major complication. Local anesthesia with sedation with propofol can be an option in anesthetic management for implantation of an ICD if an anesthesiologist cares the patient whose cardiac function is not compromised.

Study on the effectiveness of toborinone (OPC-18790) in the treatment of heart failure in patients following cardiac surgery.

Toborinone ((+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-qui nolinone, CAS 128667-95-8, OPC-18790), a novel cardiotonic agent with an inhibitory action on phosphodiesterase, is known to have a potent positive inotropic action with no positive chronotropic effect. The effectiveness of this drug in the treatment of heart failure occurring immediately after extracorporeal circulation (ECC) in cardiac surgery was investigated. The study was conducted in 12 patients with valvular heart disease showing a cardiac index (CI) of below 2.8 l/min/m2 and/or pulmonary capillary wedge pressure (PCWP) or pulmonary arterial diastolic pressure (PAD) of above 8 mmHg immediately after extracorporeal circulation. In group A (n = 6), toborinone was infused at a rate of 40 micrograms/kg/min for the first 5 min and then at 10 micrograms/kg/min for 85 min. In group B (n = 6), the drug was infused at a rate of 10 micrograms/kg/min for the entire 90 min. CI, mean systemic arterial pressure (mSAP), mean pulmonary artery pressure (mPAP), CVP, PCWP, and heart rate were measured at 5, 15, 30, 60, and 90 min after the start of infusion. The infusion volume required to maintain a constant PCWP was also estimated. In group A, CI increased rapidly and significantly from the baseline of 2.48 +/- 0.23 l/min/m2 to 3.57 +/- 1.07 l/min/m2 at 5 min after the start of infusion, and at that time mSAP was slightly decreased. In group B, CI increased gradually from the baseline of 2.53 +/- 0.18 l/min/m2 to 3.08 +/- 0.34 l/min/m2 at 15 min after the start of infusion, but almost no change was seen in mSAP. During the first 30 min, group A required a significantly larger infusion volume (983 +/- 395 ml) than group B (475 +/- 184 ml). From 30 to 90 min after the start of infusion, CI remained increased to similar levels in both groups and mSAP levels were also similar. There were no significant differences between the two groups in any other parameter. Continuous infusion of toborinone appears to be effective for treating heart failure occurring immediately after ECC in cardiac surgery. Initial loading at a rate of 40 micrograms/kg/min rapidly increased CI but was accompanied by mild hypotension. Constant infusion at 10 micrograms/kg/min brought about a more gradual effect that was similar to that of loading at 40 micrograms/kg/min, but without inducing hypotension. Thus, infusion at 10 micrograms/kg/min is considered preferable in order to avoid a larger-than-necessary infusion volume.

[Anesthetic management of left ventricular reduction surgery (Batista procedure)].

We experienced anesthetic management of left ventricular reduction surgery (Batista procedure) which is a newly developed procedure for treating end-stage dilated cardiomyopathy. The patient was a 41-year-old man who had been suffering from cardiac failure and refractory ventricular tachycardia. The anesthesia was induced and maintained with meticulous administration of fentanyl. After resection of the left ventricular free-wall, the left ventricular diastolic diameter decreased to 46 mm, from 79 mm of preoperative measurement. Weaning from cardiopulmonary bypass was successful with the use of catecholamines and intra-aortic balloon pumping. Administration of both vasodilators and phosphodiesterase inhibitors such as milrinone also contributed to reducing afterload and maintaining cardiac output. In addition to standard hemodynamic monitoring, transesophageal echocardiography provided invaluable information on determining cardiac dimensions and evaluating left ventricular wall motion.

Invasion beyond interlobar pleura in non-small cell lung cancer.

STUDY OBJECTIVE: To assess the outcome of lung cancer with invasion beyond interlobar pleura and to clarify whether it should be treated in the same way as invasion to the parietal pleura or to other visceral pleura. DESIGN: Retrospective analysis. SETTING: Tokyo Medical College Hospital. PATIENTS: Eighteen resected non-small cell lung cancers with invasion beyond interlobar pleura were studied. The outcomes of those patients, those with parietal pleural invasion, and those with other visceral pleural invasion were compared. Patients with rib invasion, mediastinal organ invasion, or distant metastasis were excluded. RESULTS: The 5-year survival rate for patients with invasion beyond interlobar pleura was 34.2% and the median survival time was 56.5 months. The outcome was significantly better than that of patients with parietal pleural invasion. There was no significant difference between the outcome of invasion beyond interlobar pleura and that of other visceral pleural invasion. In patients without lymph node metastasis, similar results were obtained. There was no difference between the outcome of patients with invasion beyond interlobar pleura, who undergo lobectomy with a parietal resection of the invaded lobe, and that of patients with visceral pleural invasion, who undergo lobectomy. CONCLUSIONS: The behavior of patients with invasion beyond interlobar pleura is different from that of patients with parietal pleural invasion and should be categorized as T2. The optimum operative method was lobectomy with only parietal resection of the invaded lobe to preserve the pulmonary function.

[Anesthetic management for Fontan procedure without the use of cardiopulmonary bypass].

We examined the anesthetic management for Fontan procedure performed without the use of cardiopulmonary bypass (Group N, n = 7) and that for equivalent procedure under cardiopulmonary bypass (Group E, n = 10) retrospectively. In Group N, surgical repairs of major vascular system were performed while bypassing the superior or inferior vena cava to the right atrium. The use of anesthetics and vasoactive agents was similar in both groups. Patients in Group N had significantly less blood loss and were extubated significantly earlier than those in Group E. However, significant metabolic acidosis was noted in Group N when reconstruction of the vascular system was completed and so-called Fontan circulation was initiated. Fontan procedure without the use of cardiopulmonary bypass may have advantage of less impairment for the cardiac performance and the pulmonary vasculature. However, its anesthetic management is another challenge to the anesthesiologist and requires meticulous control of both optimum preload and vascular resistance of the pulmonary artery.

[Blunt thoracic injury].

Of 161 patients with blunt thoracic injury, 135 were male (83.9%) and 26 were female. The most common cause of injury was traffic accidents (130 patients, 80.7%), followed by falls (22 patients), and crushing (7 patients). There were 46 third decade and 36 second decade patients. Thirty-two patients had single thoracic injury and the other had multiple organ injury. The most common associated injury was head injury (65 patients). Most traffic accidents involved motor cycle accident. Forty-four patients died, 32 within 24 hours, and 4 died to thoracic injury. These 4 patients were shock on arrival and died within 24 hours. The injury severity score, which was under 30 in 78.3% of patients, correlated to the mortality rate. Rib fracture was the most common thoracic injury in 96 patients followed by hemothorax in 91, pulmonary contusion in 79, and pneumothorax in 64. Most of the thoracic injuries were treated conservatively. Thoracotomy was performed in 6 patients. Other than one patient with rupture of the left pulmonary vein, 5 patients recovered. Continued bleeding at a rate of more than 200 ml/h from the chest drainage tube or no recovery from shock and large air leakage preventing re-expansion of the lung are indications for emergency thoracotomy. Thoracotomy should also be considered after conservative treatment in patients with continued air leakage or intrabronchial bleeding negatively affecting respiration. Indications for thoracotomy should be determined individually based on evaluating of vital sign.

Outcome of patients with early stage lung cancer.

A study was conducted to evaluate the outcomes of 79 patients with early stage lung cancer diagnosed according to the following criteria. Central tumors were located in the segmental bronchi, or more proximally, and tumor invasion was limited to the bronchial wall without lymph node or distant metastases. Peripheral tumors were located distal to the subsegmental bronchi and were less than 2 cm in greatest dimension, and invasion was limited to the visceral pleura, with no lymph node or distant metastases. The 5-year survival rate was 100% for patients with peripheral type early squamous cell carcinoma, 94.6% for those with central-type early squamous cell carcinoma, and 79.3% for those with early adenocarcinoma. The 5-year survival rate for patients with central-type squamous cell carcinoma without pericartilage layer invasion was 97.0%, and that for those with T1N0M0 peripheral squamous cell carcinoma was 100.0%. To define early stage lung cancer as curable, it should be defined as T1N0M0, peripheral squamous cell carcinoma, or central squamous cell carcinoma without pericartilage layer invasion. For other histologic types, some added parameters are needed. The rate of multiple lung cancers was 10.1% and that of multiple primary malignant disease was 13.9%. Thus, careful followup of patients with early stage lung cancer should be carried out, as second malignancies in the lung and elsewhere are commonly detected.

Results of a 28-month chronic inhalation toxicity study of formaldehyde in male Fisher-344 rats.

Male F-344 rats were exposed by inhalation to gaseous formaldehyde at 0.3, 2, and 15 ppm 6 h/day, 5 days/week for 28 months. Nasal tumors were macroscopically evident in the 15 ppm group from the 14th month and 8 of 32 rats bore such tumors at the 24th month. Histopathological examination revealed both squamous cell papillomas and carcinomas. No nasal tumors were observed in the lower exposure groups (0.3 and 2 ppm groups). In the high exposure group (15 ppm group), frequent face washing, coughing and/or crouching position, lacrimation, nasal discharge, and yellow discoloration of the haircoat were observed. Significant decrease in food consumption and body weight was noted, and 20 (88.3%) rats died by the 24th month. Reduced triglyceride levels and liver weights, presumed to be related to the drop in food intake, were also seen in the 15 ppm group. Epithelial cell hyperplasia, hyperkeratosis, and the squamous metaplasia were apparent in all exposure groups. Inflammatory cell infiltration, erosion or edema were evident in all groups, including the 0 ppm and room (RC group) controls. In this study, a no effect level of formaldehyde vapor could not be obtained because toxicological signs were obvious even with the low exposure group. The benchmark doses for squamous metaplasia and epithelial hyperplasia were 0.25 and 0.24 ppm, respectively.

Spontaneous haemothorax associated with von Recklinghausen's disease: review of occurrence in Japan.

The case history is presented of a 61 year old man with von Recklinghausen's disease who developed a spontaneous haemothorax. In spite of being asymptomatic for five days after drainage, he died as a result of fatal sudden re-bleeding. The post mortem examination showed dissection and rupture of the left subclavian artery. Microscopically, disarrangement of smooth muscle and decrease of elastic fibre was observed in the ruptured artery. Haemothorax in patients with von Recklinghausen's disease may require thoracotomy, even if the condition of the patient appears to be stable.

[Cardiac surgery using cardiopulmonary bypass in a patient with sickle-cell trait].

The sickle-cell gene is most concentrated in West Central Africa, the northeast corner of Saudi Arabia and East Central India. Sickle cell trait is the heterozygous condition for Hb S gene. Thirty to fifty per cent of their hemoglobin is Hb S and the remainder is Hb A. The sickle-cell crisis is induced by hypoxia, hypercarbia, acidosis, low flow condition, and hypothermia, which leads to vasoocclusion. A 39-year-old black man from Burkina Faso located in West Africa with left ventricular rupture was admitted for operation using cardiopulmonary bypass (CPB). He had been diagnosed as sickle-cell trait. The Hb S concentration was 36.2 per cent before operation with hemoglobin electrophoresis. During CPB, the minimum blood temperature was 31 degrees C and an aortic cross-clamp was not done. Total CPB time was 1 hour 31 minutes. Use of vasodilator and hyperventilation was effective. No neurological sequelae were observed.

Primary lung cancer of the middle lobe. Is its prognosis poor?

The right middle lobe is unique because it is surrounded by two other lobes and the pericardium, and it is the smallest lobe. The proper surgical treatment and prognosis for cancer of the right middle lobe has not been definitively established. In order to clarify its prognosis and the best operative technique, 31 surgically treated patients with lung cancer of the right middle lobe were studied clinically and pathologically. The outcome of surgical treatment of the right middle lobe cancer was compared with other locations in the lung. The 5-year survival rate of this group was 51.5%, with a median survival time of 82.3 months. For resectable cases, the outcome for carcinomas of the middle lobe was no worse than for other locations. However the rate of exploratory thoracotomy was highest for the right middle lobe. All five patients with lobectomies are alive and disease free at 26.4-151.4 months. The 5-year survival rate of 23 bilobectomies was 40.0%, with a median survival time of 48.4 months. The difference between lobectomy and bilobectomy cases was statistically significant (P < 0.025). When the tumor was limited to the completely separated middle lobe without dissemination, pulmonary or mediastinal lymph node metastasis, lobectomy was sufficient for curative treatment.

Effects of formaldehyde vapor on the nasal cavity and lungs of F-344 rats.

Histopathological and biochemical examinations of the nasal cavity and lungs of rats inhaling 145.6 ppm (high-dose) or 15.0 ppm (low-dose) formaldehyde vapor for 6 h revealed dose-related damage. The contents of non-protein SH groups (NPSH) in the nasal mucosa and lung, and lipid peroxide (LPO) in the nasal mucosa were decreased, whereas LPO was increased in the lung. The contents of triglyceride in the lung tissue and lavage, and free cholesterol in the lung were decreased, providing evidence of a suppression of surfactant production. Exposure-related changes in the nasal turbinates, trachea, and lung included hyperkeratosis of the squamous epithelium, increased secretion, and desquamation of ciliated and mucosal cells. Under the present experimental conditions, 145.6 ppm formaldehyde vapor was found to strongly affect the exposed tissues. Changes in lipid peroxide were dependent on the level of exposure.

Primary pulmonary lymphoma diagnosed by gene rearrangement: report of a case.

We report herein the case of a 59-year-old asymptomatic man who was referred to our department for investigation of an abnormal shadow detected on a routine chest roentogenogram. Computed tomography (CT) showed an infiltrative shadow and air bronchogram in the right middle lobe without mediastinal lymphadenopathy, and a right middle lobectomy was performed with hilar and interlobar lymph node excision. Microscopically, the tumor consisted of small lymphoid cells without atypia, admixed with neutrophils and other mononuclear cells, but there was no invasion of the bronchial cartilage or visceral pleura, or any lymph node involvement. Most of the tumor cells were positive for L26 and some for UCHL-1. Although a germinal center was not seen, pseudolymphoma could not be ruled out. Southern blot analysis of the frozen tissues revealed clonal rearrangements of the immunoglobulin heavy-chain JH and light-chain J kappa, whereby the tumor was diagnosed as malignant lymphoma of the small lymphocytic B-cell type. Thus, when such lymphoproliferative diseases which are difficult to diagnose are encountered, frozen tissue should be preserved for genetic analysis.

[Staged bilateral upper lobectomy of pathologically different synchronous double primary cancer].

A case of double primary lung cancer was reported, one of which was peripheral type of adenocarcinoma of the right lung and the other was central type of squamous cell carcinoma of the left. A 66-year-old male was referred to our hospital on Nov. 2 1991, because a coin lesion at the right S1 was pointed out on chest X-ray. On bronchoscopy, a nodular tumor at the orifice of the left B3 was unexpectedly found. Biopsy of the left B3 tumor and washing cytology of the right B1 led to a diagnosis of left moderately differentiated squamous cell carcinoma (clinical T1N0 M0) and right adenocarcinoma (clinical T1N0M0). A right upper lobectomy was first performed with R2 lymph node dissection on Nov. 25 1991. Post-operatively, it was confirmed that the lesion was histologically poorly differentiated adenocarcinoma of the right S1, and the pathological stage was T2N0M0. Two weeks after the operation, chemotherapy of CDDP, VDS and MMC was given because of suspicion of rapid metastasis to the left hilar lymph nodes. Left upper lobectomy with R2 dissection was performed 7 weeks after the initial operation. Pathological findings showed squamous cell carcinoma originating from B3 with inflammatory lymphadenopathy and pathological evaluation was T1N0M0. He was discharged after an uneventful course of 3 weeks after the second operation. There are many reports that limited operations are recommended for each lesion in double primary lung cancer to reserve the pulmonary function. However, limited interventions cause frequently local metastasis, especially in peripheral type adenocarcinoma more than 3 cm in diameter and central type squamous cell carcinoma with lymph node metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)

[Relationship between retained microbubbles and neuropsychologic alterations after cardiac operation].

We studied the relationship between quantity of microbubble retained in the left heart and neuropsychologic alterations after surgery in 21 patients undergoing cardiac surgery including cardiopulmonary bypass. The neuropsychologic change was evaluated by three kinds of psychological test, which mainly analyzed memory and cognition. The microbubble was continuously monitored by the long axis view of the descending aorta of transesophageal echocardiography and then quantitatively analyzed and graded by the on-line computer. More microbubbles were detected in the valve surgery requiring the intracardiac procedure than in coronary artery bypass grafting and neuropsychologic deterioration, although the relationship did not reach statistical significance. Since most of the microbubbles were detected during the unclamping of aorta and the weaning from cardiopulmonary bypass, a technical improvement of the surgical procedures could reduce them. We think that transesophageal echocardiography is useful for monitoring microbubbles during operation.

[Anesthetic management and neurological outcomes of patient for open heart surgery with infective endocarditis and neurological complications].

No reports have focused on neurological outcomes after open heart surgery of patients with infective endocarditis (IE) and neurological complications. We evaluated parameters related to anesthetic management and neurological outcomes. The subjects analyzed were 24 patients who had undergone valvular surgeries under hypothermic cardiopulmonary bypass from April 1978 to December 1990. The patients were divided into two groups according to the interval between onset of neurological complication and the time of operation: 1) acute group (within one month before the surgery: n = 11, 9.4 +/- 9 days; means +/- SD) and 2) chronic group (more than one month before the surgery: n = 13, 120 +/- 80 days). After heart surgery, 5 patients in the acute group showed newly developed neurological abnormality including death from hemorrhagic transformation, hemiplegia or aphasia. No patients in the chronic group had newly developed neurological abnormality related to the surgery. In the neurologically deteriorated patients of the acute group, interval from the onset of neurological complication to surgery was 3.5 +/- 4.5 days, whereas that of the remainders of the acute group was significantly longer (14.4 +/- 9.0 days). Intraoperative events and anesthetic management of these patients were also analyzed. However, there were no significant differences in the parameters such as cerebral perfusion pressure, arterial PaCO2, doses of anesthetics and use of vasopressors. Our results suggest that the most important factor which may influence neurological outcome was the interval between the onset of neurological abnormality and the time of operation.(ABSTRACT TRUNCATED AT 250 WORDS)