Cerebral arteriovenous oxygen content difference during barbiturate therapy in patients with acute brain damage

This study evaluated the reliability of cerebral blood flow equivalent (CBFE), which was calculated as the reciprocal of cerebral arteriovenous oxygen content difference (C(av)DO2) as a monitor during barbiturate therapy in patients with cerebral ischemic insults. A barbiturate (thiamylal) was administered at a rate of 3 mg . kg-1 . hr-1 for 2-5 days to four patients who had suffered cardiac arrest, four with acute focal ischemia, two with postoperative brain edema after neurosurgery, and one with brain damage due to asphyxia. Four of the 11 patients completely recovered neurologically (recovery group), and others had neurological sequelae or died (nonrecovery group). The mean value of CBFE in the recovery group decreased significantly with barbiturate therapy to 13 +/- 1 ml blood/ml O2 from 39 +/- 3 ml blood/ml O2 but did not decrease in the nonrecovery group. We conclude that CBFE can be useful for monitoring the effect of barbiturate therapy in ischemic brain insults.     

Effect of demeclocycline on renal function and urinary prostaglandin E2 and kallikrein in hyponatremic cirrhotics

8 cirrhotics with hyponatremia were given demeclocycline (DMC) 900 mg/day to investigate its effect on renal function, plasma renin activity, aldosterone and urinary excretion of prostaglandin E2 and kallikrein. In 7 patients DMC induced an increase of free water clearance (from -0.36 +/- 0.06 to 0.13 +/- 0.06 ml/min) and serum sodium concentration (from 125.4 +/- 0.09 to 131.1 +/- 1.0 mEq/l, mmol/l). In 5 of these patients DMC also induced a marked reduction of glomerular filtration rate (from 72.2 +/- 6.2 to 31,2 +/- 4.7 ml/min) and renal plasma flow (from 468 +/- 98 to 195 +/- 55 ml/min) which could not be explained on the basis of hypovolemia. In each case this renal impairment was not associated with changes in urinary concentration of beta 2-microglobulin, urinary casts excretion, fresh urine sediment or urine protein content and disappeared after discontinuation of the drug. DMC induced a marked increase in the urinary excretion of prostaglandin E2 (from 0.82 +/- 0.27 to 6.16 +/- 1.91 ng/min) in 6 out of the 7 patients who responded to DMC and a marked reduction in urinary kallikrein (from 16.1 +/- 4.4 to 4.2 +/- 1.6 pkat/min) in the 5 patients who developed renal insufficiency. The serum DMC concentration was greater than 5 micrograms/ml in all patients who responded to DMC, greater than 8 micrograms/ml in all cases who developed renal insufficiency and of 3 micrograms/ml in the case not responding to DMC. (ABSTRACT TRUNCATED AT 250 WORDS)     

A possible circadian rhythm of susceptibility to thiamylal

A circadian rhythm of the susceptibility to thiamylal was evaluated in 30 patients. They were divided into two groups; 15 patients were induced around 9 AM (Morning-group) and the rest were in the early afternoon (Afternoon-group). The induction was performed by intravenous administration of thiamylal sodium. Parameters measured were the time and doses of thiamylal sodium to obtain the loss of consciousness and the loss of eyelash reflex. The results were as follows; the doses of thiamylal sodium to obtain the loss of consciousness were 3.5 +/- 0.6 mg.kg-1 (mean +/- SD) in Morning-group, and 4.1 +/- 0.4 mg.kg-1 in Afternoon-group, respectively. Thus, larger doses of thiamylal were necessary to obtain the loss of consciousness in Afternoon-group than in Morning-group (P less than 0.01). The doses of thiamylal sodium to obtain the loss of eyelash reflex were 4.4 +/- 0.8 mg.kg-1 in Morning-group and 5.0 +/- 0.6 mg.kg-1 in Afternoon-group, respectively. Also, larger doses of thiamylal were necessary to obtain the loss of eyelash reflex in Afternoon-group than in Morning-group (P less than 0.05). This study suggests that a circadian rhythm of the susceptibility to thiamylal exists in humans.     

Apnea testing in the diagnosis of brain death. Clinical and physiological observations

The absence of spontaneous respiration is a crucial determinant in the diagnosis of brain death, but standardized criteria for apnea testing have not been established. Guidelines are proposed based on the results of 51 apnea tests and associated physiological measurements. In patients who fulfilled all other conventional criteria for brain death, three exhibited non-repetitive back arching and shoulder shrugging when CO2 pressures reached 41 to 51 mm Hg during apnea testing. These respiratory-like movements were ineffective for ventilation and were not reproducible on the following day at the same of higher pCO2. The nature of these movements, evoked potential testing, and autopsy results suggest that they were not triggered by normal medullary centers, and that these patients were, in fact, brain-dead. In four other patients with severe brain damage sparing only the medulla, normal spontaneous ventilation resumed at CO2 pressures of 30 to 39 mm Hg (mean 34 mm Hg). High arterial oxygen tension raised this apnea point slightly, but spontaneous breathing always began at CO2 pressures lower than 40 mm Hg. This level is therefore adequate to stimulate medullary respiration in patients with severe brain damage who are not brain-dead. In brain-dead patients, pCO2 rises slowly during apnea (2.58 +/- 0.85 mm Hg/min), in part because CO2 production is diminished (1.8 +/- 0.23 ml/min/kg). These data allow estimation of a desired length of an apnea test and standardized interpretation of results.     

Changes in plasma fibronectin levels in burn patients

Plasma fibronectin was determined in 180 healthy individuals. No significant difference was found between males and females: therefore the values were pooled. The mean value was 286.94 +/- 51.35 micrograms/ml. In 24 patients with burns covering 30-95 per cent of the total body surface area (TBSA), plasma fibronectin was determined sequentially. There was a significant lowering in plasma fibronectin (FN) values in all cases on post-burn day 1 (112.56-185.85 micrograms/ml) and post-burn day 2 (44.03-298.0 micrograms/ml). The concentrations returned to within the normal range in 19 survivors within 3-6 days. In five non-survivors, plasma FN levels fell progressively until death. In another nine patients with burns ranging from 3 per cent to 25 per cent TBSA, plasma FN level was found to be normal on post-burn day 1. The likely causes of the reduced concentrations of plasma fibronectin in patients with burn injuries are briefly discussed. It seems that the level of plasma fibronectin may be used as a prognostic index in burn patients.     

Effects of long term inhaled high dose beclomethasone dipropionate on adrenal function.

Studies of adrenal function were performed on 54 asthmatic patients who were taking long term high doses of inhaled beclomethasone dipropionate ranging from 500 to 2000 micrograms/day for between six and 60 months. Of the 43 patients taking up to 1500 micrograms/day, 39 (91%) had normal basal plasma cortisol concentrations and normal short tetracosactrin responses and 24 hour urinary free cortisol excretion was within the normal range in eight of nine patients tested. Some evidence of adrenal suppression was found in patients taking 2000 micrograms/day, with basal plasma cortisol below the normal range in four out of 11 patients and 24 hour urinary free cortisol excretion below the normal range in five out of six patients tested. Only one of the 11 patients taking 2000 micrograms/day had a short tetracosactrin response below the normal range: the mean rise in plasma cortisol was, however, significantly lower in this group than in those taking 1000 micrograms/day (328 (SE 30) and 506 (34) nmol/l respectively) (p less than 0.01). Patients taking more than 1500 micrograms/day of inhaled beclomethasone may require systemic corticosteroids during prolonged stress.     

Functional treatment of acromegaly by transsphenoidal microsurgery

The authors have analyzed the results from 41 acromegalic patients who underwent transsphenoidal surgery. In 31 patients, postoperative growth hormone (GH) levels fell and remained below 10 ng/ml. This represents an endocrinological "cure" of 78%. In the remaining 10 cases, postoperative GH values have not stabilized below 10 ng/ml, although seven show some clinical improvement. The results were particularly good in those cases of localized adenomas, which allowed a selective removal while maintaining pituitary function within normal limits in 65.5% of cases. The postoperative GH level in this group fell and remained below 10 ng/ml in more than 90% of cases. Four patients required reoperation to normalize the GH levels which had not been sufficiently modified after the first operation; only one of them remained with plasma GH levels above normal limits. There were no deaths in this series. Rhinorrhea occurred as a postsurgical complication in four cases. In three this disappeared with bed rest and lumbar drainage; in the other, surgical repair was necessary. The occurrence of surgical complications has decreased as our experience has increased, and the need for reoperation has been unusual after the first year of our study.     

Complete neurological recovery in a patient with decerebrate rigidity following cardiac arrest from acute airway obstruction by advanced laryngeal cancer

A 59-year-old man presented with severe dyspnea caused by advanced laryngeal cancer. As he had disregarded the dyspnea for a month, we did not have enough information about the extent of the tumor. The pulse oximeter showed 88% with oxygen inhalation. Because of severe dyspnea, he could not maintain supine position. Fiberoptic laryngoscopy showed tumor bulk obstructing airway directly. In the operating room, at first, a cricothyroid membrane puncture was attempted under local anesthesia but the procedure was abandoned when the patient became hypoxic and unconscious. Immediately tracheostomy and cardiopulmonary resuscitation were performed. Tumor bulk had displaced the trachea and surrounding structures, making a tracheostomy difficult. Nine min after loss of consciousness, a secure airway was obtained. However, he was still unconscious and developed characteristic decerebrate rigidity. Therefore the patient was treated with infusion of thiamylal and free radical scavenger and mild hypothermia therapy (bladder temperature 34 degrees C). On the fifth day of this treatment, after rewarming and discontinuation of thiamylal, the patient responded to command. He recovered with no neurological deficits. This case suggests that combined treatment with barbiturate, free radical scavenger, and mild hypothermia therapy is effective to minimize ischemic brain damage after cardiopulmonary resuscitation.     

Alfentanil Blocks Reflex Pupillary Dilation in Response to Noxious Stimulation But Does Not Diminish the Light Reflex

Background: Estimation of the micro-agonist opioid effect in anesthetized and paralyzed patients is often imprecise and can be obscured by concomitant administration of drugs that affect the sympathetic nervous system, such as beta-adrenergic blocking agents. As an alternative to hemodynamic measures of opioid effect, the authors tested the hypothesis that the pupillary light reflex or pupillary reflex dilation correlated with alfentanil concentrations during isoflurane anesthesia.

Methods: Six volunteers were anesthetized on 4 days with 0.8% isoflurane. Alfentanil was administered intravenously to target total plasma concentrations of 0, 25, 50, and 100 ng/ml. A 5-s tetanic electrical stimulus was applied to the skin. Pupil size and the pupillary light reflex were recorded before and after alfentanil administration, and before and for 8 min after the stimulus.

Results: Alfentanil exponentially impaired reflex pupillary dilation, decreasing the maximum response amplitude from 5 mm at 0 ng/ml, to 2.3 mm at 25 ng/ml, to 1.0 mm at 50 ng/ml, and finally to 0.2 mm at 100 ng/ml. In contrast, only the highest concentration of alfentanil depressed the dilation of the pupil in the first 2 s after the stimulus. Alfentanil administration had no effect on the pupillary light reflex.     

Methohexital plasma concentrations in children following rectal administration

Despite the increasing use of rectal methohexital as a premedicant-induction agent in pediatric anesthesia, there are no data to confirm the assumption that low plasma methohexital concentrations are the cause of inadequate sedation of children and that high concentrations are associated with the loss of consciousness. Plasma methohexital concentrations were determined in 20 ASA Class I children, ages 2-7 yr, after the rectal administration of methohexital (25 mg/kg). Seventeen of the 20 children in this study fell asleep after receiving the drug and achieved peak plasma concentrations greater than 2 micrograms/ml. The maximum plasma methohexital concentration in children that did not fall asleep was less than 2 micrograms/ml. The mean time to the onset of sleep after drug administration was 8.3 min (at which time the mean plasma concentration was 4.4 micrograms/ml). The mean peak plasma concentration and the mean time to peak plasma concentration were 4.7 micrograms/ml and 13.9 min, respectively. Loss of consciousness after rectal administration of methohexital correlates well with the plasma concentration of the drug.     

回肠膀胱扩大术联合髂腰肌盆底肌加强术治疗神经源性膀胱的疗效分析

目的 探讨去黏膜带蒂回肠膀胱扩大术联合髂腰肌盆底肌加强术治疗神经源性膀胱的疗效.方法 前瞻性研究去黏膜带蒂回肠膀胱扩大联合髂腰肌盆底肌加强术治疗神经源性膀胱的疗效.神经源性膀胱患者12例.男9例,女3例.年龄18 ～ 27岁,平均25岁.临床表现为不同程度的尿失禁.病程6 ～ 64个月,平均23个月.应用超声、膀胱造影、尿动力学等检查前瞻性比较术前和术后1年的尿动力学参数,上尿路形态和肾功能情况.结果 12例手术顺利.术后出现切口延迟愈合2例,肠梗阻1例,膀胱腹壁尿瘘1例,未出现黏液尿.术后1年1例因发热性泌尿系感染行自我清洁间歇导尿,11例为腹压排尿.术前膀胱输尿管反流8例,术后反流消失5例,反流程度改善3例.术前肾功能不全5例,术后血肌酐水平下降至正常范围3例.术前和术后1年最大膀胱压测定容量[( 247±27)和(412±32) ml]、膀胱顺应性[(4.4±1.2)和(26.2±4.0)ml/cm H2O,1 cm H2O =0.098 kPa]、相对安全容量[(206±24)和(368±26) ml]、最大尿流率[(11±2)和(20±3)ml/s]、残余尿量[(136±25)和(26±8)ml]、逼尿肌漏点压[(63.1±4.9)和(17.8±3.6)cm H2O]比较差异均有统计学意义(P＜0.05).结论 去黏膜带蒂同肠浆肌层膀胱扩大联合髂腰肌盆底肌加强术可有效治疗神经源性膀胱.     

Plasma prilocaine and mepivacaine concentrations after combined lumbosacral plexus block

In a pharmacokinetic study of combined sciatic/3-in-1 block for lower limb surgery, the two moderate-acting local anaesthetics prilocaine and mepivacaine were compared. The mean maximum venous plasma concentrations of mepivacaine were more than twice as high as when prilocaine was used as anaesthetic (5.1 micrograms/ml vs. 2.37 micrograms/ml). When used in combination with the former, ornipressin did not reduce plasma concentrations of mepivacaine to values which were below the threshold for toxic symptoms (5-6 mg/ml). The peak plasma concentrations exceeded the threshold of 5 micrograms/ml in four of the nine patients of the mepivacaine group (maximum value 7.21 mg/ml) and in two of the nine patients of the mepivacaine+ornipressin group (maximum value 8.61 micrograms/ml).     

Alfentanil's analgesic, respiratory, and cardiovascular actions in relation to dose and plasma concentration in unanesthetized dogs

Relationships between plasma concentrations of alfentanil and its analgesic, respiratory, and cardiovascular effects were determined in dogs. To avoid drug interaction, trained, unanesthetized, spontaneously breathing dogs were used. After a control period in the awake state, alfentanil was injected in increasing amounts (10, 20, 80, 160, and 320 micrograms/kg) at 5-min intervals to a total dose of 590 micrograms/kg administered over 20 min. The effects were observed on pain responses (heart rate and blood pressure changes and somatic reactions to tail clamping), respiration (respiratory rate, oxygen consumption [VO2], blood gas tensions) and circulation (heart rate and blood pressure). The plasma concentration-effect curves, derived by relating the changes in multiple variables from the awake state to the corresponding plasma concentrations (range 8-5079 ng/ml), plateaued at and around 200 ng/ml during the injection period but were displaced in parallel to two-fold higher concentrations during recovery, which resembles acute tolerance. At maximally effective analgesic concentrations, which precipitated profound cardiorespiratory slowing with conspicuous hypoxemia, the VO2 of 4.4 +/- 0.3 ml X kg-1 X min-1 corresponded with the calculated metabolic rate but increased to 6.3 +/- 1.6 ml X kg-1 during recovery. The analgesic action of alfentanil, which cannot be separated from its depressant cardiorespiratory effects and maximally effective analgesic concentrations (between 200 and 400 ng/ml), apparently does not jeopardize the adequacy of tissue oxygenation in dogs.     

Evaluation of criteria for discontinuing mechanical ventilatory support.

Thirty-three patients who required short-term postoperative mechanical ventilatory support were studied to compare different criteria established to initiate weaning from mechanical ventilation. Intermittent mandatory ventilation criteria (i.e., decreasing mechanical respirator rate as long as the arterial (pHa) remains above 7.35) and conventional criteria (ie, vital capacity greater than 15 ml/kg and peak negative pressure greater than 20 cm H2O) were compared to determine which would more rapidly predict a patient's ability to sustain total spontaneous respiration. All patients were eventually weaned from mechanical ventilation and had their tracheas extubated. Twenty-one patients maintained a pHa of greater than 7.35 during total spontaneous ventilation before they would, or could, meet conventional criteria for initiating a trial of spontaneous respiration (P less than .001). Seven patients simultaneously met both criteria for maintaining total spontaneous ventilation and the remaining five patients met conventional criteria before intermittent mandatory ventilation criteria. In the latter group, the pHa decreased below 7.35 during spontaneous respiration but in only one patient did it fall below 7.30. Our findings suggest that a patient's ability to maintain a pHa of greater than 7.35 while decreasing the frequency of mechanical ventilator breaths is more accurate than peak negative pressure and vital capacity for predicting ability to sustan adequate spontaneous respiration.     

Reversible nephrotoxicity after overdose of colloidal bismuth subcitrate

Although toxicity due to acute and chronic use of bismuth salts is well known, nephrotoxicity after ingestion of colloidal bismuth has been reported in few cases so far. Here we report the first case of acute renal failure (ARF) due to colloidal bismuth subcitrate overdosage in childhood. A 2-year-old boy was admitted to the hospital 6 h after ingestion of 28 De-Nol tablets (colloidal bismuth subcitrate 8.4 g). On admission, physical examination was unremarkable and he showed no signs of encephalopathy. Initially gastric lavage was performed then appropriate fluid therapy was started. ARF associated with uremia and oliguria developed on day 2 and peritoneal dialysis therapy was prescribed on day 4 for 10 days. Blood and urine bismuth levels were 739 μg/l and 693 μg/l, respectively, 10 days after the pills had been taken. His urine volume gradually increased and plasma BUN and creatinine levels decreased during peritoneal dialysis. On day 20 post-admission, plasma BUN and creatinine were 14 mg/dl and 0.7 mg/dl, respectively. Blood bismuth levels were 96 μg/l on day 60 and 12 μg/l on day 105. Now the patient is well and has no problem. This case suggests that ARF may develop in children following colloidal bismuth subcitrate overdosage; the prognosis is good, and peritoneal dialysis may be useful in these cases. Received: 25 February 2000 / Revised: 5 December 2000 / Accepted: 17 January 2001     

Hypothalamic pituitary function in brain death patients--from blood pituitary hormones and hypothalamic hormones

According to the report of the Health and Welfare Ministry's research committee on brain death (1985), "brain death is defined as an irreversible cessation of the total brain function including brain stem." However, in brain death patients, whether the hypothalamic function which belongs to the brain stem function has completely ceased or not is unknown. In order to evaluate the hypothalamic function in brain death patients, the blood levels of the pituitary hormones and hypothalamic hormones were measured, and anterior pituitary stimulation test with triple bolus injection (TRH 500 micrograms, LH-RH 100 micrograms, regular insulin 0.3-0.7 unit/kg) was performed. The subjects were 13 brain death patients whose clinical states fully satisfied the criteria proposed by the committee. 1) The average blood levels of anterior pituitary hormones in these brain death patients were within normal range, and that of growth hormone was more than the twice of the normal level. 2) The blood anterior pituitary hormones were detectable in almost all cases even several days after the diagnosis of the brain death. 3) LH reserve was maintained in three cases. FSH reserve was maintained in three cases. Prolactin reserve was maintained in two cases. TSH reserve was maintained in one case. 4) Blood ADH (antidiuretic hormones) were detectable in 7 cases out of 9 cases. The blood ADH level of one case, in particular, was rather high (above 10 pg/ml). 5) Histopathologically anterior pituitaries were examined in three autopsy cases. The central necrotic areas were observed in all cases, but normal pituitary tissues existed peripherally. And all anterior pituitary hormones could be recognized immunohistochemically. 6) The blood levels of the hypothalamic hormones (GRF, CRF, LH-RH) were measured in four cases. The hypothalamic hormones were detectable in all cases. In one case, the levels of GRF were within normal range even 9 or 15 days after the diagnosis of brain death.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of antiemetics on pupillary reflex dilation during epidural/general anesthesia

The effect of dopamine D2 receptor antagonists, such as chlorpromazine and haloperidol, on pupil size in awake subjects suggests that these drugs might also alter pupillary reflex dilation and pupil size during general anesthesia. Forty-seven patients undergoing lower abdominal surgery under combined epidural/general anesthesia were randomized to receive one of the 5 following open labeled drugs: 10 mL saline, 0.13 mg/kg ondansetron, 0.25 mg/kg metoclopramide, 0.5 mg/kg metoclopramide, or 0.02 mg/kg droperidol. Three measurements of reflex dilation were taken at 5-min intervals and after the last measurement (time 0) the drug was administered. Measurements were then taken 5, 10, 20, and 40 min after I.V. drug administration. Reflex dilation was induced by intermittent noxious stimulation of the C5 dermatome with a tetanic electric current (60-70 mamp, 100 Hz, 3-s duration) after a stable level of epidural analgesia had been established with 3/8% bupivacaine and maintained with a continuous infusion. Metoclopramide produced a small decrease in pupil diameter and transiently depressed reflex dilation, whereas droperidol decreased pupil size at 10 min and depressed reflex dilation throughout the 40-min study period. Maximal change in reflex dilation was -6.6 +/- 3.3 mm-sec after droperidol. Ondansetron had no effect on pupil diameter or reflex dilation. When pupillary diameter measurements are used to gauge opioid levels during experimental conditions or during surgical anesthesia, antiemetic medication acting on the dopamine D2 receptor should be avoided. IMPLICATIONS: Miosis is often considered an effect of opioid administration during general anesthesia, but other drugs, such as antiemetics, might produce a similar effect on the pupil. This study demonstrates that 2 antiemetics, droperidol and metoclopramide, constrict the pupil and block the pupillary dilation brought about by nociceptive stimuli.     

Evaluation of a breast cyst fluid protein detectable in the plasma of breast carcinoma patients.

A radioimmunoassay has been developed for one of the major proteins isolated from human breast cyst fluid. Immunologically this protein is identical to a protein present in both human milk and saliva. Ninety-two normal women had plasma levels of this protein below 100 ng/ml (range 7-81 ng/ml; mean 31 ng/ml), and 85% had plasma levels below 50 ng/ml. More than one-half of the women with active gross cystic disease of the breast had plasma levels above 50 ng/ml. None of these women, however, had plasma levels above 150 ng/ml. A significant percentage of women with advanced breast carcinoma have been found to have plasma concentrations of this protein greater than 150 ng/ml.     

Measurements of CSF biochemical tumor markers in patients with meningeal carcinomatosis]

CSF beta--glucuronidase, polyamines and carcinoembryonic antigen (CEA) were analyzed in 16 patients with meningeal carcinomatosis from solid tumors in systemic organs, 27 with benign brain lesions, 11 with primary brain tumors, 14 with metastatic brain tumors and 5 with leptomeningeal dissemination of other malignant diseases. beta--glucuronidase levels in all cases of meningeal carcinomatosis, meningeal gliomatosis and meningeal lymphoma were higher than 100 micrograms/dl/hr. On the other hand, levels in all cases of benign brain lesions were below 100 micrograms/dl/hr. Levels of beta--glucuronidase in the cases of metastatic brain tumors returned to normal levels after tumor resection. Levels of beta--glucuronidase and polyamines were not high in the cases with positive cytology in CSF after tumor resection. The polyamine level seemed to be dependent on the growth rate of the disease and was shown to below 0.05 nmol/ml in all cases after resection of the metastatic brain tumors. Cystic fluid of both benign and malignant tumor showed high levels of beta--glucuronidase and polyamines except for spermidine and spermine levels in a suprasellar cyst. Some cases of meningeal carcinomatosis with high levels of serum CEA did not always show high levels of CSF CEA. In the surgical cases with a metastatic brain tumor, the cases with leptomeningeal, especially dural attachment showed high levels of beta--glucuronidase and CEA preoperatively, but they returned to normal after surgery. In 2 cases of meningeal carcinomatosis treated by intrathecal chemotherapy with MTX and Ara-C, CSF beta--glucuronidase and CEA showed clinical condition better than the cell count in CSF decreased rapidly following chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)