Effects of hyperosmolality on the central nervous system and intracranial hemorrhage

The relationship between hyperosmolality and intracranial hemorrhage as well as brain dysfunction was studied. Hyperosmolality was induced by continuous infusion of hyperosmotic solutions, such as 7% sodium bicarbonate (1,666 mOsm/1), 4.64% sodium chloride (1,666 mOsm/1), 20% glucose (about 1,200 mOsm/1), 20% mannitol (about 1,200 mOsm/1), and 10% glycerol with 0.9% sodium chloride and 5% fructose (about 2,000 mOsm/1). 1) Intracranial hemorrhage was observed without exception after the rabbits had died of hyperosmolality due to the infusion of these agents. The intracranial hemorrhage was mostly subdural hemorrhage in the subtentorial region. 2) The plasma osmolality just before death varied according to the agents administered and was lowest in the case of 7% sodium bicarbonate with a level of 441 mOsm/1. 3) The plasma osmolality in the case of 10% glycerol was higher than the case of 20% mannitol at the death. 4) The arousal reaction was suppressed by hyperosmotic solutions which contain sodium ions, and when the plasma osmolality surpassed 320 mOsm/1, dysfunction of the CNS began to appear. 5) The evoked muscular discharges caused by stimulation of the midbrain reticular formation were suppressed only by the administration of 7% sodium bicarbonate, so this result is related to alkalosis.     

The effect of oral glycerol on intraventricular pressure in man

Oral glycerol was administered to eight patients with meningeal carcinomatosis or acute leukemia in whom ventricular catheters and Ommaya reservoirs had been implanted for the purpose of intrathecal chemotherapy or chemoprophylaxis. Intraventricular pressure was monitored continuously via the Ommaya reservoirs before and after single doses of 0.5, 1.0 or l.5 gm per kilogram of body weight. The interrelationship between initial pressure, change in pressure, serum osmolarity, and duration of action was investigated, and the ratio of CSF-to-plasma osmolarity was determined 4 to 5 hours after glycerol administration. The effects of chronic 6-hourly and 4-hourly 1 gm per kilogram glycerol doses were studied in a patient with meningeal carcinomatosis and increased intracranial pressure. Our data suggest that as a cerebral dehydrating agent oral glycerol is most effective in patients with markedly increased intracranial pressure. A single 1 gm per kilogram dose is adequate to lower raised intraventricular pressure acutely, but its effect is short-lived. Continuous oral administration must be carefully monitored to avoid the establishment or a reverse osmotic gradient, secondarily increased intracranial pressure, and clinical deterioration.     

Effect of NIK-242 inj. (20% erythritol) on intracranial pressure in dogs with acute obstructive hydrocephalus

The effects of NIK-242 inj. (20% erythritol) on intracranial pressure (ICP) and serum osmotic pressure (Osm. P) were investigated in dogs with acute obstructive hydrocephalus, and they were compared with those of 20% mannitol or 10% glycerol in 5% fructose and 0.9% saline. Animals were divided into 5 groups (n = 6 in each group) and treated with either NIK-242 inj. (0.5 g/kg, 1.0 g/kg, 2.0 g/kg), mannitol (1.0 g/kg) or glycerol (0.5 g/kg). These drugs were administrated intravenously for 10 min. NIK-242 inj. rapidly reduced ICP and increased Osm. P. There was correlation between changes of ICP and Osm. P. The regression equation was Y = -6.489 X + 726.206 (n = 104, p less than 0.00001, R = -0.655). The effects were dose-dependent, but there were no significant differences between the effects of NIK-242 inj. 1.0 g/kg infusion and 2.0 g/kg infusion. The most appropriate dose of NIK-242 inj. was 1.0 g/kg, in which group ICP was significantly lower than the initial pressure until 120 minutes after administration (p less than 0.05). The maximum reduction rate of ICP [(initial ICP-minimum ICP)/initial ICP X 100] was 83.6 +/- 10.6% at 22.7 +/- 3.0 min. after administration. It was 61.6 +/- 6.9% at 19.3 +/- 1.6 min. in mannitol group and 77.1 +/- 7.4% at 15.0 +/- 0.8 min. in glycerol group. There was no rebound phenomenon on ICP during 150 min., but there was one in mannitol group and five in glycerol group. NIK-242 inj.(ABSTRACT TRUNCATED AT 250 WORDS)     

复方甘油治疗脑水肿降低颅内压的疗效观察

通过32例高颅压患者甘油和甘露醇交替给药的疗效比较，结果显示两药的总有效率及降ICP作用类似；但两药降ICP的显效时间、持续时间不同，尿量及尿比重也有显著差异。所以甘露醇适于急性颅压增高患者的急救，而甘油适于需长期脱水治疗的患者。     

Rebound phenomenon of mannitol and glycerol: clinical studies

A rebound phenomenon after infusion of hypertonic solution of mannitol and glycerol on raised intracranial pressure was studied by epidural pressure recordings for 65 patients. The mean age of the patients was 50 years with a range of 29 to 73 years. The diagnoses of above patients were as follows; 29 were cerebral aneurysms, 19 were brain tumors, 10 were hypertensive intracerebral hemorrhages, 4 were cerebral contusions, 2 were arteriovenous malformations, and one was cerebral abscess. Four methods of infusion were performed. In group A, 0.5 g/kg of mannitol was infused within 15, 30 or 60 minutes. In group B, 1.0 g/kg of mannitol was infused within 30, 60 or 90 minutes. In group C, 0.5 g/kg of glycerol in 5% fructose was infused within 30, 60 or 90 minutes. In group D, 1.0 g/kg of glycerol in 5% fructose was infused within 60, 120 or 180 minutes. The following observations were examined in all patients. (1) The occurrence of the rebound phenomenon. (2) The rate of the raised intracranial pressure (ICP) compared to the ICP before infusion of these hypertonic solutions. (3) The duration of the rebound phenomenon. Results: A rebound phenomenon was found 23% in all patients, and 12% in the mannitol groups and 34% in the glycerol groups. The dose and the rate of mannitol infusion did not influence the occurrence of the rebound phenomenon. In contrast, in the glycerol groups, the infusion method did influence the occurrence of the rebound phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mathematical model of brain edema and optimal control of intracranial pressure

It is necessary to analyse various parameters responding to hypertonic solutions such as mannitol or glycerol, in order to achieve the best therapeutic results for patients having increased intracranial pressure (ICP). The responding model system for the ICP composing of multi-compartments of blood and brain tissue was mathematically introduced. By analysing the changes of the ICP under administration of glycerol using this system, the mathematical model for brain edema was developed. The cause of water transfer in this model system was indicated as the difference of the osmotic pressure and determined as ICP increasing factor, V. It was demonstrated that this theoretical model responded quite similarly to human ICP monitored by sumulating this system for clinical cases. The ICP controller was further developed. The automatic control of ICP was clinically achieved by using this controller. The minimal effective dose of glycerol can be automatically administered by presetting a desirable ICP for each patient.     

重型颅脑损伤患者甘露醇、速尿和白蛋白降颅压作用的临床观察

目的观察甘露醇、速尿和白蛋白在不同使用方法和剂量上的降颅压效果,探讨临床合理的药物降颅压方法。方法124例重型颅脑损伤患者随机分为5组,全部进行持续颅内压(ICP)监测,连续观察静脉使用甘露醇、速尿和白蛋白后的ICP、血钾、血钠和血尿素氮(BUN)的变化。结果甘露醇和速尿降ICP作用明显(P<0.05);半量甘露醇加速尿或白蛋白降ICP作用显著(P<0.05)且持续时间长(P<0.05);降ICP的过程中可能出现电解质、肾功能的异常和ICP的反跳现象。结论半量甘露醇+速尿降ICP的方法值得临床提倡;半量甘露醇联合使用中、大剂量白蛋白在有条件的情况下也是适宜的降ICP方法。     

Surgical Treatment of Intracranial Arteriovenous Malformation

Abstract

The surgical indication and techniques of intracranial arteriovenous malformations are discussed, on the basis of 203 experiences with AVMs. A special key point in our surgical techniques is described as follows. The feeding arteries of the AVM–or the main artery at the base of the brain, which is the original source of the feeding artery–are identified and prepared, and then temporary clips are placed on these arteries to produce vascular occlusion prior to the dissection of the AVM itself. During these procedures, 20% of mannitol should be administered to prolong the permissible time of cerebral artery occlusion. The administration method of mannitol is described in detail including dose and time schedule. The new prolongation method of temporary occlusion time, for which mannitol with fiuorochemicals permits longer occlusion time, is also introduced.     

Intracranial volume–pressure relationships during experimental brain compression in primates: 3. Effect of mannitol and hyperventilation

In 10 anaesthetized and ventilated baboons a steady level of raised intracranial pressure was achieved by graduated inflation of an extradural balloon. Measurements were made of the ventricular fluid pressure, and of the change in this pressure after injection of 0·05 ml into the ventricle, the volume–pressure response. This response was studied at normocapnia and at hypocapnia (induced by hyperventilation), and before and after the intravenous administration of mannitol under normocapnic and hypercapnic conditions. During hypocapnia, ventricular fluid pressure and the volume–pressure response were reduced equally. Mannitol, however, caused a greater reduction in the volume–pressure response than in ventricular fluid pressure. The intravenous administration of mannitol therefore produces a beneficial effect on intracranial capacitance which is greater than observation of intracranial pressure alone indicates.     

Effects of intravenous mannitol on EEG recordings in stroke patients.

OBJECTIVES: To evaluate the usefulness of continuous EEG monitoring of stroke patients during and after intravenously infused mannitol. METHODS: Patients were rapidly administered 50 g of intravenous mannitol solution with continuous EEG monitoring for 3h pre- and post-drug infusion in the neurological intensive care unit. Visual and spectral analyses of EEG recording pre- and post-mannitol infusion were carried out. RESULTS: The study consisted of 47 patients. Of 38 patients with intracranial hemorrhage, 33 had abnormal EEG findings pre-mannitol administration. After mannitol therapy, visual analysis of the drug-induced EEG changes showed that the EEG findings were unchanged in 13 patients, demonstratively improved in 22 patients, and worse in 3 patients. The spectral analysis demonstrated that mannitol-induced EEG changes increased in alpha power and decreased in delta power in the lesion hemispheres, especially in the central and middle temporal areas. Maximal effects occurred 30 min post-mannitol infusion, and remained significant for 2h post-infusion. Of the 9 patients with cerebral infarction, only one with diffuse background slowing of one-side dominance pre-mannitol improved after the infusion of mannitol. CONCLUSIONS: The results of our investigation indicated that continuous EEG monitoring of mannitol treatment can reflect the brain edema, raised ICP in stroke patients, and provide assessment the drugs effects of antiedema and intracranial pressure lowering in vivo.     

The treatment of raised intracranial pressure following aneurysm surgery

The effect of intravenous mannitol infusion and withdrawal of cerebrospinal fluid on the intracranial pressure and clinical state was studied in 26 patients with raised intracranial pressure after direct surgery for ruptured aneurysm. Each method decreased the mean intracranial pressure by about 60% of the pre-treatment level. The maximal decrease following mannitol occurred after 60-90 minutes and generally lasted between three and four hours. The effects of mannitol did not decrease when repeated infusions were necessary. Rebound increases in the intracranial pressure following infusion were not observed. Withdrawal of cerebrospinal fluid lowered the intracranial pressure immediately and the effect persisted for approximately 60 minutes. This could be repeated as often as necessary and was without systemic disturbance, although a patent intraventricular catheter was necessary. The two methods could be used simultaneously.     

Usefulness of intracranial pressure monitoring and EEG analysis in a child with acute encephalitis

The usefulness of continuous intracranial pressure (ICP) monitoring and the correlation between ICP and electroencephalographic findings were investigated in a 6-year-old boy with acute encephalitis. On admission he was comatose in a decerebrate posture. ICP was continuously monitored by the epidural transducer and controlled with hyperventilation, fluid restriction and administration of mannitol, glycerol and pentobarbital to keep below 20 mm Hg. The inotropic agents such as dopamine and dobutamine were also given to maintain the cerebral perfusion pressure (CPP) at 50 mm Hg or greater. At the same time with ICP monitoring, EEG records were obtained with scalp electrodes at monopolar T3-A1 and T4-A2 regions according to the 10-20 international system on an analog tape simultaneously with a data recorder. The records were digitized at 50 samples/sec, and the high-order auto-regressive (AR) power spectrum was calculated with a minicomputer PFU-1200 (Fujitsu Co Ltd.). At pressures greater than 25 mm Hg in ICP, the total power of the high-order AR activity of EEG was apparently decreased. The results indicated that the AR power spectral analysis of EEG is sensitive method for obtaining valuable information regarding the electrical brain activity and intracranial pressure.     

连续血液滤过联合甘露醇治疗颅内高压合并肾功能衰竭的临床研究

目的 探讨连续血液滤过联合甘露醇在颅内高压合并肾功能衰竭治疗中的应用价值。 方法 对珠江医院重症医学科收治的9例颅内高压合并肾功能衰竭患者行2～3次连续血液滤过联合甘露醇治疗,监测治疗前后患者颅内压数值、血肌酐及胱抑素浓度。 结果 在应用连续血液滤过联合甘露醇治疗后,患者颅内压数值较治疗前明显降低,血肌酐及胱抑素浓度较治疗前明显下降,差异有统计学意义(P＜0.05)。1例脑干出血患者于治疗第2天死于多器官功能衰竭,其余8例患者均未出现脑疝,平稳渡过脑水肿高峰期。 结论 连续血液滤过联合甘露醇是一种快速有效的治疗颅内高压合并肾功能衰竭的方法。     

Fructose-added glycerol (Glyceol) for therapy of elevated intracranial pressure: analysis of the side effects of long-term administration in a multi-institutional trial

The effects of long-term administration of fructose-added glycerol solution (Glyceol): 10% glycerol, 5% fructose, 0.9% sodium chloride; 600-2000 ml/d intravenously for 7-63 d) were evaluated in a multi-institutional trial involving 1346 cases. Improvement of the neurological signs and symptoms of elevated intracranial pressure was recognized by responsible physicians in close association with the administration of Glyceol (75.1%). The intracranial pressure measured directly also decreased in most cases following the administration of Glyceol (81.2%). No significant changes were observed in serum electrolytes and osmolarity at the end of the long-term administration. Unfavourable changes in clinical conditions which were considered very likely or suspected to be due to the long-term administration of Glyceol were recorded in 2 cases (0.1%) or 13 cases (1.0%), respectively. Most of these changes were abnormalities of serum electrolytes. It appeared, however, that the abnormalities of serum electrolytes may be readily correctable, and rarely induced if standard care of the serum water-electrolyte balance is carried out and unless too large doses are employed. Other changes appeared to be related more to preexistent complications and/or the administration of other drugs, rather than to the administration of Glyceol alone. Thus, administration of Glyceol appeared feasible for the therapy of elevated intracranial pressure over the long term.     

Effect of uridine 5'-diphosphate on cryogenic brain edema in rabbits

This study was undertaken to examine the effect of uridine 5'-diphosphate, administered intravenously or intraperitoneally, on cold injury-induced brain edema in rabbits. Bolus injection or continuous intravenous infusion of uridine 5'-diphosphate 26 hours after a lesion was established had adverse effects, such as increased intracranial pressure and lowered systolic arterial blood pressure and cerebral perfusion pressure for approximately 10-29 minutes, but these parameters did not change appreciably from 29 minutes to 3 hours after administration. Intraperitoneally administered uridine 5'-diphosphate did not affect these parameters appreciably during 3 hours. Thus, the intravenous administration of uridine 5'-diphosphate is harmful under neurosurgical conditions. In contrast, 10 mg/kg/day i.p. uridine 5'-diphosphate pretreatment and posttreatment, beginning 24 hours before and continuing until 24 hours after the insult, significantly reduced neurologic abnormalities, Evans blue extravasation, water content in the injured gray matter, and intracranial pressure without affecting water content in the white matter. Intravenous dexamethasone pretreatment and posttreatment in this setting significantly reduced only neurologic abnormalities. However, there were no significant differences between intraperitoneal uridine 5'-diphosphate and intravenous dexamethasone effects on cold-injured brain.     

经不同途径应用万古霉素治疗兔细菌性脑室炎的效果

目的 探讨经不同途径应用万古霉素治疗兔细菌性脑室炎的效果。方法 将新鲜配制的标准表皮葡萄球菌混悬液0.5 ml以0.1 ml/min的速度缓慢注入侧脑室将制作兔细菌性脑室炎模型。将50只细菌性脑室炎成年新西兰大白兔随机分为单纯静脉组（Ⅰ组,静脉注射万古霉素）、单纯动脉组（Ⅱ组,颈内动脉注射万古霉素）、联合静脉组（Ⅲ组,先静脉注射甘露醇,继而注射万古霉素）、联合动脉组（Ⅳ组,先颈内动脉注射甘露醇,继而注射万古霉素）,对照组（Ⅴ组,静脉注射生理盐水）,每组10只。所有动物均12 h给药一次,直至动物死亡,最多给药6次。结果 Ⅰ组、Ⅱ组给药后96 h内无动物死亡,Ⅲ组给药后72~96 h死亡5只,Ⅳ组给药后72~96 h死亡1只,Ⅴ组给药后24 h内全部死亡。首次给药后1 h,Ⅰ、Ⅱ、Ⅲ、Ⅳ组脑脊液万古霉素浓度分别为（40.02±0.07）μg/L、（89.11±0.19）μg/L、（69.02±0.17）μg/L、（118.13±0.31）μg/L;两两比较,均有统计学差异（P<0.05）。给药72 、96 h,Ⅳ组肛温、外周血白细胞数、脑脊液白细胞数均明显低于Ⅲ组（P<0.05）。结论 经颈内动脉联合应用甘露醇和万古霉素治疗细菌性脑室炎的效果优于单纯静脉或动脉注射万古霉素以及经静脉联合应用甘露醇和万古霉素的效果。     

Intravenous versus intramuscular atropine in ECT.

Twelve patients receiving ECT consented to random assignment to either intravenous or intramuscular administration of atropine for a total of 48 ECTs. There were no statistically significant differences between routes of administration in heart rate, blood pressures, or sialorrhea, but intravenous administration eliminated one injection per treatment and the development of dry mouth and tachycardia between the intramuscular injection and ECT. The authors recommend that atropine for ECT be administered intravenously.     

The mechanism of intracranial pressure-reducing effect of mannitol

The effect of mannitol to decrease the raised ICP is well documented and mannitol is now widely used in clinical practice. However, its mechanism of lowering ICP still remains controversial, especially under the condition of vasogenic edema. The objective of this study is to reexamine and delineate the mechanism of ICP reducing effect of mannitol, using quantitative vasogenic edema model, specific gravimetric technique to measure the brain water content, and the method to estimate the CSF dynamics without disturbing the physiological condition of intracranial compartments in cats. Quantitative increase of water content of the white matter was produced by the infusion of 0.5 ml of normal saline though stereotaxically inserted 25-G needle into the left frontal white matter. In control group, cats were sacrificed and water content of the gray and white matter of each coronary sliced brain was measured by specific gravimetric technique. In the mannitol group, 20% of mannitol (2 g/kg) was administrated via femoral vein within 3 minutes. The maximum reduction of ICP was achieved at the average of 30 minutes. At this time, the cats were sacrificed and the water content of brain was measured in the same way as in the control group. PVI, Ro, If (Marmarou) were calculated before and after mannitol administration. In parameter group, BP, ICP, CVP, serum osmotic pressure and osmolarity were measured without terminating the experiment. The changes of water content of the gray and white matter before and after mannitol administration in the area of infusion edema were 80.7% to 80.8% and 76.8% to 77.1% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

不同剂量的甘露醇对血浆渗透压的影响

目的 观察不同剂量甘露醇对血浆渗透压的影响，以指导临床合理用药。方法 33例颅内压增高的病人随机分成二组，第1组17例，给予20％甘露醇0．5g/kg；第2组16例，给予20％甘露醇1．0g/kg，两组均6-8h输注一次。监测两组病人每日首剂甘露醇前、后的血浆渗透压数值。结果 两组病人甘露醇使用前、后血浆渗透压差值比较有统计学意义（P〈0．01）。连续多日反复使用甘露醇后，可引起血浆渗透压基础值逐渐增高，且使用时间越长，血浆渗透压基础值越高。结论 对于甘露醇，切莫盲目使用大剂量。从安全的角度考虑，提倡使用小剂量的甘露醇，有条件者应在用药期间监测血浆渗透压。     

Effect of steroids on intracranial pressure and pressure-volume index in patients with hydrocephalus

It is well-established that steroids (glucocorticoids) have a beneficial clinical effects on patients with increased intracranial pressure, but there is still a controversy on the mode of action of steroids. The purpose of this study is to investigate the effects of steroids on continuous intracranial pressure and on intracranial compliance using pressure-volume index (PVI). Thirteen hydrocephalic patients, ranging from 9 to 70 years old, without intracranial mass lesion nor brain edema were studied. The patients were divided into two groups. Group I: Five patients were monitored the continuous intracranial pressure for 24 hours again following the administration of steroids on continuous intracranial pressure. The method of the administration of steroids was that betamethasone 8 mg for initial dose was administered intravenously and followed by 4 mg intramuscularly every 6 hours. There was little change in the baseline pressure and the amplitude on continuous intracranial pressure monitoring before and after the administration of steroids. But the maximum pressure and the maximum amplitude significantly decreased after the administration of steroids. The % time B-wave and the maximum continuous time of B-wave also decreased significantly. Group II: Eight patients were studied in order to investigate the effects of steroids on the intracranial compliance. PVI was measured according to Marmarou's method before and after the intravenous administration of steroids (beta-methasone 0.5 mg/kg). PVI increased in 7 out of 8 cases after the administration of steroids, which was statistically significant. It can be concluded that steroids increase the intracranial compliance and inhibit the rise of intracranial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)