Intracranial hypertension in patients with ruptured intracranial aneurysm.

Simultaneous continuous recording of intracranial pressure (ICP) and systemic blood pressure was carried out in 26 patients admitted within 1 week after subarachnoid hemorrhage (SAH) due to a ruptured intracranial aneurysm. The patients were graded as described by Hunt and Hess. Recordings were made for 1 to 5 days. The more impaired the consciousness, the higher the rate of ICP. In Grade III, IV, and V patients, the mean ICP level was in the range of 15 to 40 mm Hg, 30 to 75 mm Hg, and exceeded 75 mm Hg, respectively. A definite correlation between vasospasm shown by cerebral arteriogram and the clinical grade was not observed. In our series of ICP recordings, we never observed a typical plateau wave. The variations of ICP seen in Grade III and IV patients were the B- and C-waves (15 to 45 mm Hg in amplitude) described by Lundberg, and those in Grade V patients were the high amplitude monotonous waves synchronous with the arterial pulses (15 to 40 mm Hg in amplitude). These phenomena may indicate that Grade III and IV patients with SAH are in a condition of cerebral vasomotor instability, and Grade V patients have cerebral vasomotor paralysis.

Vasorelaxant effects of oxpentifylline and theophylline on rat isolated aorta.

The mechanism of the relaxation response of rat aorta to the phosphodiesterase inhibitors oxpentifylline and theophylline was studied. Oxpentifylline induced a greater vasorelaxation response in the intact strips than in those without endothelium. The endothelium-dependent relaxation response to oxpentifylline was inhibited by nitro-L-arginine but not by indomethacin, and the endothelium-independent relaxation response was potentiated by the combination with isoprenaline but not sodium nitroprusside. Theophylline induced a similar relaxation response in vascular strips with and without endothelium. The relaxation response to theophylline was not inhibited by indomethacin or nitro-L-arginine in intact strips, but was potentiated by combination with isoprenaline or sodium nitroprusside in the denuded strips. These results suggest that the two phosphodiesterase inhibitors oxpentifylline and theophylline induce vasorelaxation by different mechanisms. Oxpentifylline can induce both endothelium-dependent relaxation, which is probably mediated by an endothelium-derived relaxing factor, and endothelium-independent relaxation, which may be due to an inhibitory action on phosphodiesterase of vascular smooth muscle. In contrast, theophylline can induce endothelium-independent relaxation alone, without modulation by the endothelium.

[Simultaneous administration of ethanol emphasizes the effect of methamphetamine on central nervous system in rat with high alcohol preference].

We studied about influence of alcohol preference and of simultaneously administered ethanol (EtOH) on the effect of methamphetamine (MA) on the central nervous system neurochemically and behavioral pharmacologically using two strains of rat with high or low preference for alcohol (HAP and LAP). In the neurochemical study, we determined dopamine (DA) and serotonin (5-HT) level in striatum and nucleus accumbens (N.Acc) by means of brain microdialysis after administration of MA 1 mg/kg alone (LAP-MA group, HAP-MA group) or EtOH 2 g/kg + MA 1 mg/kg (LAP-EtOH/MA group, HAP-EtOH/MA group) every 20 minutes for 10 sessions. In the behavioral pharmacological study, we observed rat's behavior in the open field and performed scoring according to Locomotion-Stereotypy (L-S) rating scale by Ellinwood every five minutes, and counted locomotion and rearing by means of infrared beam cutting every 20 minutes after administration of MA 1 mg/kg alone (LAP-MA group, HAP-MA group) or EtOH 2 g/kg + MA 1 mg/kg (LAP-EtOH/MA group, HAP-EtOH/MA group). When MA was given alone, HAP rat showed no significant difference in locomotion, rearing and L-S score compared to LAP rat, although HAP rat showed significantly lower elevation of DA and 5-HT in both striatum and N.Acc. When EtOH was simultaneously administered with MA, in LAP rat, DA and 5-HT elevation in the striatum and N.Acc showed no significant differences between LAP-EtOH/MA group and LAP-MA group. Locomotion and rearing reduced and L-S score temporarily reduced significantly in LAP-EtOH/MA group compared to LAP-MA group. However in HAP rat, HAP-EtOH/MA group showed significantly higher DA and 5-HT elevation in both striatum and N.Acc, and also showed significantly higher L-S score and higher locomotion count compared to HAP-MA group. Our results indicate that effect of MA may be influenced by alcohol preference, and that simultaneous administration of EtOH emphasizes the effect of MA on central nervous system in rat with high alcohol preference.

[Effects of norepinephrine and phentolamine on acute intracranial hypertension].

It is accepted that cerebrovascular dilatation is a constant response during the advanced stage of intracranial hypertension. Severe intracranial hypertension ultimately associates with profound vasodilatation and reduces cerebral blood flow to zero. This irreversible state is called cerebral vasomotor paralysis by Langfitt et al (1965). The rich adrenergic nerve supply of the cerebral vessels suggests that pressor amines possibly affect the cerebral circulation and the cerebral vascular tone. This study is to investigate the reactivity of norepinephrine and phentolamine on intracranial pressure (ICP) in patients with severe intracranial hypertension. The ICP and systemic blood pressure (SBP) monitorings were carried out continuously after the evacuation of intracerebral hematomas due to ruptured intracranial aneurysms. Severe intracranial hypertension due to brain swelling was observed in these patients. Three stages were defined according to the reactivity to norepinephrine and phentolamine on the ICP. In Stage I, norepinephrine caused a transient decrease in the ICP and phentolamine caused a marked rise in the ICP. Stage II was marked by the absence of the ICP response to norepinephrine and phentolamine. During Stage III, the ICP changes synchronously with a variation of the SBP after the administration of norepinephrine and phentolamine. In Stage I patients, the mean ICP level was between 500-1000 mmH2O. Tracing of the ICP in this group showed transient rises called pressure waves and the waves were recurring increases in the ICP to value of 300-500 mmH2O superimposed on an elevated level of the ICP. On the other hand, in Stage II and III patients, the ICP level exceeded 1000 mmH2O. Tracing of the ICP in these groups showed only variations by the arterial pulses. The patients in Stage I had a well prognosis for life if proper treatments such as continuous ventricular drainage were carried out. The patients in Stage II and III had a poor prognosis for life inspite of continuous ventricular drainage. There are varying stages in cerebrovascular dilatation accompanying intracranial hypertension. We have no information on the mechanism of this cerebrovascular dilatation at present. However, we speculate that the pressor amines such as norepinephrine may partly participate in the mechanism responsible for the vasodilation. So, we attempt to grade the degree of this vasodilatation according to the reactivity of norepinephrine and phentolamine on the ICP. It is presumed that cerebrovascular dilatation is slight and reversible in Stage I patients, whereas cerebrovascular dilatation is profund and irreversible in Stage II and III patients. Continuous ICP recording and examination of the reactivity to norepinephrine and phentolamine on the ICP are valuable when considering the prognosis for life in patients with severe intracranial hypertension.

[Intracranial pressure in patients with diffuse cerebral arterial spasm following ruptured intracranial aneurysms (author's transl)].

Intracranial pressure (ICP) was recorded continuously for 2 to days in 12 pre-operative patients with angiographic evidence of diffuse cerebral arterial spasm due to ruptured intracranial aneurysm. The ICP pattern of the low level (below 15 mmHg) and flat type was registered in the early stage of the arterial spasm in 11 patients in whom the ICP recording was made within 11 days after the hemorrhagic attack. During the period of low and flat ICP pattern, 6 patients showed little or no neurological deterioration whereas 5 patient showed impaired consciousness or neurological deficits. In 9 out 11 patients, the low level of ICP was followed by an abnormal deterioration. Continuous ventricular drainage was performed to control the secondary increased ICP in 7 patients and they survived, 4 of them with good results but remaining 3 with severe neurological deficits.

[The anesthesiologist's role in the French emergency medical system].

The present system of French emergency medicine and its philosophy were described from my experience at SAMU (service d'aide medicale urgente). Three factors of emergency medicine; pre-hospital care, emergency transport and emergency information service are managed by anesthesiologists. Anesthesiologists on duty at the tele-medicine center give medical team instructions to start at once. The team is composed of an anesthesiologist, a nurse and an ambulancier. They start to give intensive care medicine to critically ill patients on the spot. The philosophy of SAMU is that doctors should go out of the hospital. Anesthesiologists in the area organize the emergency medical system in France.

[The present status and problems of repatriation in France].

In France, repatriation, the inter-continental or interhospital critical care transport, is done on a large scale mainly by private companies with sophisticated medical knowledge, techniques and equipment. They offer a great assistance to SAMU when a disaster occurs. It is notable that almost all doctors who work for these companies are anesthesiologists and trained in SAMU. Repatriation is a large field involving critical care transport which includes intensive care medicine and disaster medicine as well as emergency medicine. One of the most important things about repatriation is that the judgement should be done and means of transport of the patient should be decided based purely on medical grounds.

[Effect of nafamostat mesilate on the renin-aldosterone system].

It has been reported that continuous intravenous infusion of nafamostat mesilate (FUT) produces hyperkalemia due to reduced urinary excretion of potassium. The present study was performed to see whether renin-aldosterone effect is involved in this inhibition of potassium excretion. Ten patients were studied who had been given this drug (4 mg.hr-1) to prevent postsurgical pancreatitis or DIC. Urine potassium output decreased significantly from 44 +/- 5 microEq.min-1 prior to administration of FUT to 18 +/- 4 microEq.min-1 in 3 hours, sodium/potassium ratio increased significantly from 1.7 +/- 0.7 prior to administration of FUT to 5.4 +/- 3.3 in 5 hours; and plasma aldosterone decreased significantly from 92 +/- 24 pg.ml-1 prior to administration of FUT to 63 +/- 22 pg.ml-1 in 6 hours. The results suggest that hyposecretion of aldosterone may be one of the main causes of hypokalemia. Reduced secretion of aldosterone may be due to other factors than the suppression of renin-angiotensin system.

[The false positive reaction of the Triage panel drug-of-abuse by herbal drugs ma-huang (Ephedra sinica (Ephedraceae))].

We investigated false-positive reactions obtained from a drug screening test using a Triage panel. We detected 2 cases giving false-positive reaction for AMP (amphetamine, methamphetamine) during the screening of 187 normal subjects. Subsequent follow up testing by high-performance liquid chromatography (HPLC), showed both to be false-positive reactions. As both cases have a history of ingesting the herbal drug, Ma-huang (Ephedra sinica (Ephedraceae)), containing ephedrine, we examined the relationship between false-positive reactions on Triage and Ma-huang. All urine samples collected from 7 healthy volunteers following administration of Ma-huang indicated AMP positive on Triage. Also a high ratio of AMP positives was observed in the patients who were administered Ma-huang-containing drugs at the hospital. However, none of them were identified as true-positives by HPLC or gas chromatography mass spectrometry (GC/MS) analysis. The extract of Ma-huang contained in herbal drugs, which otherwise contain neither amphetamine nor its derivatives, gives (AMP) positive indications on Triage. We speculate that unidentified components of Ma-huang cause the false-positive reactions. We suggest that follow-up tests by GC/MS or HPLC are needed wherever a positive result is obtained from a screening test by Triage. Furthermore, it will be established to continue collecting information on prescribed and non-prescribed drugs.