The immunomodulatory compound 2-acetyl-4-tetrahydroxybutyl imidazole causes sequestration of lymphocytes in non-lymphoid tissues

Variceal bleeding is the second cause of death in cirrhosis. To achieve haemostasis, sclerotherapy (or banding) is the first line treatment but vasoactive drugs (terlipressin or somatostatin) are an alternative and even a complement. Porto-systemic shunt is to be rapidly considered if a second endoscopic treatment has failed. Primary prevention lies on beta-blockers (propranolol or nadolol). Organic nitrates are an alternative and even a complement. Secondary prevention lies on banding or sclerotherapy; beta-blockers are an alternative and even a complement.     

Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding

BACKGROUND: Patients who have bleeding from esophageal varices are at high risk for rebleeding and death. We compared the efficacy and safety of endoscopic sclerotherapy with the efficacy and safety of nadolol plus isosorbide mononitrate for the prevention of variceal rebleeding. METHODS: Eighty-six hospitalized patients with cirrhosis and bleeding from esophageal varices diagnosed by endoscopy were randomly assigned to treatment with repeated sclerotherapy (43 patients) or nadolol plus isosorbide-5-mononitrate (43 patients). The primary outcomes were rebleeding, death, and complications. The hepatic venous pressure gradient was measured at base line and after three months. RESULTS: Base-line data were similar in the two groups, and the median follow-up was 18 months in both. Eleven patients in the medication group and 23 in the sclerotherapy group had rebleeding. The actuarial probability of remaining free of rebleeding was higher in the medication group for all episodes related to portal hypertension (P = 0.001) and variceal rebleeding (P = 0.002). Four patients in the medication group and nine in the sclerotherapy group died (P = 0.07 for the difference in the actuarial probability of survival). Seven patients in the medication group and 16 in the sclerotherapy group had treatment-related complications (P = 0.03). Thirty-one patients in the medication group underwent two hemodynamic studies; 1 of the 13 patients with more than a 20 percent decrease in the hepatic venous pressure gradient had rebleeding, as compared with 8 of the 18 with smaller decreases in the pressure gradient (P = 0.04) for the actuarial probability of rebleeding at two years). CONCLUSIONS: As compared with sclerotherapy, nadolol plus isosorbide mononitrate significantly decreased the risk of rebleeding from esophageal varices.     

A prospective randomized trial comparing somatostatin and sclerotherapy in the treatment of acute variceal bleeding

Somatostatin and endoscopic sclerotherapy are widely used in the treatment of acute variceal bleeding. Although objective evidence does exist about the advantages of either treatment, data comparing both procedures are scarce. In order to compare the effectiveness and safety of somatostatin and sclerotherapy in the treatment of acute variceal bleeding, 70 consecutive cirrhotic patients suffering from esophageal variceal hemorrhage and meeting the inclusion criteria were randomly assigned to treatment with somatostatin (35 patients) or sclerotherapy (35 patients). No differences in age, sex, alcohol intake, etiology of cirrhosis and severity of liver failure were found between groups. Failure of treatment (defined as persistence of bleeding despite therapy or subsequent rebleeding within the 48-hr trial period) occurred in seven patients (20%) in the somatostatin group and in six (17.1%) in the sclerotherapy group (NS). Early rebleeding occurred in seven of 28 patients (25%) in the somatostatin group and in five of 29 (17.2%) in the sclerotherapy group (NS). Mortality within the first 6 wk was no different between both groups: 10 (28.5%) and eight (22.8%) in the somatostatin and sclerotherapy groups, respectively. Sclerotherapy, but not somatostatin, was associated with major complications in five cases (14.2%) (p = 0.026), two of which resulted in patient's death. These results suggest that somatostatin is safer, and as effective as sclerotherapy, in controlling acute variceal bleeding until an elective treatment can be established.     

Guidance of intracoronary radiation therapy based on dose-volume histograms derived from quantitative intravascular ultrasound

BACKGROUND/AIMS: The risk factors for esophageal variceal rebleeding are little known. Variceal pressure is one of the major determinants of variceal rupture, but the relationship between variceal pressure and variceal rebleeding during maintenance sclerotherapy has not been determined. This study was undertaken to evaluate the relationship between variceal pressure/gradient change and variceal rebleeding during maintenance sclerotherapy. METHODS: Patients with liver cirrhosis and recent esophageal variceal hemorrhage underwent consecutive variceal pressure measurements by direct puncture of the varices before each elective sclerotherapy. RESULTS: In 46 patients, the initial variceal pressure was no different regardless of age, sex, underlying etiology or hepatic reserve. Variceal pressure was higher in large varices, varices with more severe red wale markings, and varices with slower reduction in size during maintenance sclerotherapy. A larger volume of sclerosant was required to eradicate large varices, varices with more severe red wale markings, and varices with slower reduction in size during maintenance sclerotherapy. There was a positive correlation between initial variceal pressure and total amount of sclerosant (r=0.485, p=0.001). Initial variceal pressure was not related to rebleeding. Variceal pressure increased more in patients with rebleeding from varices per se (n=7) than in those without rebleeding (n= 24). There was no difference in pressure change between patients without rebleeding (n=24) and those with rebleeding from variceal ulcers (n=7). CONCLUSIONS: Large varices, severe red color signs and slow reduction in variceal size were associated with higher initial variceal pressure, and more sclerosant was required to eradicate the varices. An increase in variceal pressure during maintenance sclerotherapy indicates a higher risk of variceal rebleeding, but not of variceal ulcer rebleeding.     

A learning curve for laparoscopic splenectomy at an academic institution

Variceal hemorrhage continues to be a major cause of morbidity and mortality in cirrhotic patients. Transjugular intrahepatic portosystemic shunt (TIPS) is gaining wide acceptance as a treatment for several complications of portal hypertension. The aim of the current randomized study was to compare the transjugular shunt and endoscopic sclerotherapy (ES) for the prevention of variceal rebleeding (VB) in cirrhotic patients. Forty-six consecutive cirrhotic patients with variceal bleeding were randomly allocated to receive either transjugular shunt (22 patients) or ES (24 patients) 24 hours after control of bleeding. VB (50% vs. 9%) and early (first 6 weeks) VB (33% vs. 5%) were significantly more frequent in sclerotherapy patients; the actuarial probability of being free of VB was higher in the shunt group (P <.002). Eight patients (33%) of the sclerotherapy group and 3 patients (15%) of the shunt group died; the actuarial probability of survival was higher for the shunted patients (P <.05); 6 patients in the sclerotherapy group and none in the shunt group died from VB (P <.05). No difference was found in the proportion of patients with clinically evident hepatic encephalopathy (HE). These results show that the transjugular shunt is more effective than sclerotherapy in the prevention of both early and long-term VB. Moreover, a significant improvement in survival was found in the shunt group.     

Prevalence of hypothalamic-pituitary imaging abnormalities in impotent men with secondary hypogonadism

BACKGROUND & AIMS: Combining endoscopic sclerotherapy with ligation has been proposed to hasten variceal eradication. A randomized trial was performed comparing combination ligation plus sclerotherapy with ligation alone in patients with major bleeding from esophageal varices. METHODS: Forty-one patients were randomly assigned to receive ligation or ligation plus 1 mL 1.5% tetradecyl injected just above each band. Treatment was repeated weekly until varices were eradicated. Repeat endoscopy was performed for rebleeding and every 3 months after eradication. RESULTS: No significant differences were found between combined therapy and ligation in rebleeding (29% vs. 30%), blood transfused (3.1 +/- 1.1 vs. 2.0 +/- 0.8 U), hospital days (9.3 +/- 2.1 vs. 7.5 +/- 1.2), complications (29% vs. 10%), or deaths (14% vs. 15%) during a mean follow-up period of 28 weeks. Combined therapy required significantly more sessions to achieve eradication (4.9 +/- 0.6 vs. 2.7 +/- 0.4) and greater time per treatment session (18.3 +/- 1.7 vs. 13.3 +/- 0.5 minutes). CONCLUSIONS: Combined ligation plus sclerotherapy does not reduce the number of treatment sessions required for variceal eradication as compared with ligation alone. Combined therapy lengthens the time required for treatment without improving efficacy or decreasing complications. Thus, combined ligation and sclerotherapy should not be used to treat patients with bleeding esophageal varices.     

Sclerotherapy versus sclerotherapy and propranolol in the prevention of rebleeding from oesophageal varices: a randomised study

BACKGROUND: This trial was carried out to assess the value of propranolol in the prevention of recurrent variceal bleeding when combined with longterm endoscopic sclerotherapy. PATIENTS AND METHODS: Two hundred patients (161 male, 39 female, age range 20-68 years) with portal hypertension resulting mainly from schistosomal periportal fibrosis or posthepatitic cirrhosis presenting with their first episode of haematemesis or melena, or both were included. This was confirmed endoscopically to result from ruptured oesophageal varices. After initial control of bleeding, patients were randomised into two groups: group 1 treated with endoscopic sclerotherapy alone and group 2 treated with sclerotherapy plus propranolol. They were followed up for two years. RESULTS: Group (2) had a lower rebleeding rate (14.3% v 38.6% in group 1), lower variceal recurrence after obliteration (17% v 34% in group 1), longer period between variceal obliteration and recurrence (36 weeks v 21 weeks in group 1); but no change in mortality (12% in both groups). CONCLUSIONS: Patients treated with sclerotherapy should be given propranolol for longterm management.     

Sclerotherapy versus ligation in hemorrhage caused by rupture of esophageal varices. Direct meta-analysis of randomized trials

OBJECTIVES: To compare the advantages of endoscopic ligation and endoscopic sclerotherapy for bleeding esophageal varices, published randomized clinical trials were critically reviewed by meta-analysis. Only ten clinical trials concerning a history of recent or active bleeding esophageal varices were included. METHODS: The methodology, population, treatment and outcomes of each relevant trial were evaluated by duplicate independent review. RESULTS: Endoscopic sclerotherapy compared to banding ligation significantly increased the rate of rebleeding (OR: 1.6; 95% IC: 1.1-2.3) without increasing early mortality compared to endoscopic banding ligation (OR: 1.3; 95% IC: 0.8-1.9). The rate of varice eradication associated with these two types of treatment was not different (OR: 0.9; 95% IC: 0.6-1.3) but was obtained more quickly with endoscopic banding ligation (3.8 +/- 1.6 versus 5.8 +/- 2.2; P < 0.05). The rate of complications was higher after sclerotherapy (OR: 2.5; 95% IC: 1.7-3.7), in those cases with a positive heterogeneity test. CONCLUSIONS: This meta-analysis shows a lower morbidity with endoscopic banding ligation in patients with variceal hemorrhage. The most important advantage of endoscopic banding ligation was the reduction of the rate of rebleeding.     

Hepatorenal syndrome. Long-term treatment with terlipressin as a bridge to liver transplantation

In patients with hepatorenal syndrome (HRS), 4-hr administration of a vasopressin analog has recently been shown to benefit renal blood flow and renal function. However, long-term effects and tolerance of this treatment have not been reported. We report a case of HRS that was controlled by the vasopressin analog, terlipressin. Because HRS repeatedly relapsed when treatment was discontinued, terlipressin, 2 mg/day was administered for 67 days, until liver transplantation could be performed in a patient with normal renal function. Except for limited cutaneous necrosis at an injection point, prolonged treatment with this vasopressin analog was well tolerated.     

Compressive sclerotherapy monitored by ultrasound]

Echosclerotherapy and sonographic control of aimed sclerotherapy resp. is a major advance in the treatment of chronic venous insufficiency. It facilitates not only aimed administration of highly active substances but ensures above all prevention of serious complications. Functional examination of the venous system helps to locate relatively accurately the sites of pathological reflux which are in the first place responsible for the development of the whole symptomatology and it prevents the administration of excessive amounts of sclerotizing substances into intact portions of the venous system. Similarly as Baccaglini et al. (1995) the authors achieved by compressive sclerotherapy with monitoring by ultrasound occlusion of up to 90% important reflux sites such as the saphenofemoral and saphenopopliteal orifice which are to a great extent responsible for serious clinical symptoms.     

Bivalent hapten-bearing peptides designed for iodine-131 pretargeted radioimmunotherapy

BACKGROUND: Few studies have compared vasoactive drugs with endoscopic sclerotherapy in the control of acute variceal haemorrhage. Octreotide is widely used for this purpose, but its value remains undetermined. AIMS: To compare octreotide with endoscopic sclerotherapy for acute variceal haemorrhage. PATIENTS: Consecutive patients with acute variceal haemorrhage. METHODS: Patients were randomised at endoscopy to receive either a 48 hour intravenous infusion of 50 pg/h octreotide (n = 73), or emergency sclerotherapy (n = 77). RESULTS: Overall control of bleeding and mortality was not significantly different between octreotide (85%, 62 patients) and sclerotherapy (82%, 63 patients) over the 48 hour trial period (relative risk of rebleeding 0.83; 95% confidence interval (CI) 0.38 to 1.82), irrespective of Child's grading or active bleeding at endoscopy. One major complication was observed in the sclerotherapy group (aspiration) and two in the octreotide group (pulmonary oedema, severe paralytic ileus). During 60 days of follow up there was an overall trend towards an increased mortality in the octreotide group which was not statistically significant (relative risk of dying at 60 days 1.91, 95% CI 0.97 to 3.78, p = 0.06). CONCLUSIONS: The results of this study indicate that intravenous octreotide is as effective as injection sclerotherapy in the control of acute variceal bleeding, but further controlled trials are necessary to evaluate the safety of this treatment.     

Histotopographic distribution of placental inflammation: analysis of 22 cases

OBJECTIVES: Acute bleeding from esophageal varices is a major complication of cirrhosis. Despite the large number of published studies no predictive factors of control of bleeding have been identified. We assessed the clinical and biological factors predictive of bleeding control within the first 2 weeks after a bleeding episode in a homogeneous group of patients enrolled in a large multicenter trial, who underwent a standardized emergency sclerotherapy session. METHODS: 101 patients with cirrhosis were enrolled. All had endoscopy-proven variceal bleeding, and the interval between hematemesis or melena and emergency sclerotherapy was always less than 24 hours. A second sclerotherapy session and other methods for the prevention of rebleeding were allowed after 5 days. RESULTS: Treatment failed in 16 patients after 24 hours and in a total of 33 patients after 15 days. Three of the 17 variables included in multivariate logistic analysis were associated with failure at 24 hours: encephalopathy (P = 0.006, OR = 4.0), blood transfusion prior to sclerotherapy (P = 0.012, OR = 6.2) and previous propranolol therapy (P = 0.022, OR = 4.6). Two variables were associated with failure between 24 hours and day 15 in patients successfully controlled after 24 hours: an interval between the onset of bleeding and sclerotherapy of less than 12 hours (P = 0.010) and blood transfusion (P = 0.018). After 15 days, three variables were associated with failure in a multivariate Cox model: encephalopathy (P = 0.0025, OR = 2.3), time to sclerotherapy (P = 0.022, OR 2.3) and blood transfusion before sclerotherapy (P = 0.0005, OR = 4.0). CONCLUSION: Encephalopathy, the severity of bleeding, assessed in terms of transfusion requirements, and the time between clinically overt bleeding and sclerotherapy are the main predictive factors of failure of the control of bleeding after emergency sclerotherapy for acute bleeding from esophageal varices.     

Endoscopic sclerotherapy versus variceal ligation in the long-term management of patients with cirrhosis after variceal bleeding. A prospective randomized study

BACKGROUND/AIMS: Long-term endoscopic injection sclerotherapy of oesophageal varices prevents rebleeding in patients with cirrhosis surviving an acute variceal bleeding episode. However, this treatment is associated with a substantial complication rate. Endoscopic band ligation is a newly developed technique in an attempt to provide a safer alternative. The aim of this study was to compare the efficacy and safety of injection sclerotherapy versus variceal ligation in the management of patients with cirrhosis after variceal haemorrhage. METHODS: Seventy-seven patients with cirrhosis who proved to have oesophageal variceal bleeding were studied. After initial control of haemorrhage by sclerotherapy, 40 of the patients were randomly assigned to sclerotherapy and 37 to ligation. Both procedures were performed under midazolam sedation at intervals of 7-14 days until all varices in the distal oesophagus were eradicated or were too small to receive further treatment. RESULTS: The eradication of varices required a lower mean number of sessions with ligation (3.7 +/- 1.9) than with sclerotherapy (5.8 +/- 2.7, p = 0.002). The mean duration of follow-up was similar in both groups (15.6 months +/- 7.3 and 15 +/- 7.4, respectively). The proportion of patients remaining free from recurrent bleeding against time was significantly higher in the ligation group as compared to the sclerotherapy group (chi 2 = 3.86, p = 0.05). Only 13 patients (35%) developed complications in the ligation group as compared to 24 (60%, p = 0.05) in the sclerotherapy group. The mortality rate was similar in both groups (20% and 21%, respectively). CONCLUSIONS: Variceal ligation is better than sclerotherapy in the long-term management of patients with cirrhosis after variceal haemorrhage which was initially controlled with sclerotherapy.     

Medical prophylaxis of haemorrhage from oesophageal varices in patients with liver cirrhosis

Haemorrhage from oesophageal varices is a life-threatening event in patients with liver cirrhosis. About 40-80% of patients surviving the first bleeding suffer a recurrence within 1 year. This high recurrence rate substantially contributes to the mortality in patients with liver cirrhosis. Therefore, various treatment regimens in both primary and secondary prophylaxis were studied. Most experience in medical primary prophylaxis was collected with beta-blockers, mainly propranolol. Treating patients with oesophageal varices with propranolol significantly reduces the incidence of first variceal bleeding. However, the effect on mortality is marginal, and primary prophylaxis is generally not recommended in these patients. Several studies support the hypothesis that medical prophylaxis with beta-blockers is more effective in reducing the rate of first oesophageal bleeding in patients with a high risk of haemorrhage, such as those with very large varices with red spots. A score to assess an individual patient's risk of variceal bleeding would be helpful, but until such a score has been validated, no general rule for this treatment decision can be given. In secondary prophylaxis, both beta-blockers and endoscopic therapy (sclerotherapy or ligation of the varices) are effective in lowering the rate of rebleeding. However, the effect on mortality was not significant in most studies. Several studies comparing the efficacy of medical prophylaxis and endoscopic treatment showed advantages of the endoscopic therapy with a greater reduction in recurrent bleeding episodes. However, medical prophylaxis with beta-blockers has the important advantage of being immediately effective, whereas endoscopic procedures provide the best protection against recurrent bleeding after complete obliteration of the varices. Therefore, in the first weeks and months of endoscopic therapy, additional treatment with beta-blockers may further reduce the risk of rebleeding. Only half of all studies on this topic reported a significant advantage with this combined therapy. Therefore, it seems reasonable to restrict this approach to patients with a high risk of rebleeding, such as patients with large sclerotherapy-derived oesophageal ulcers.     

Evaluation of trauma care in a developing country highlighted by a major aircraft accident

Transjugular intrahepatic portosystemic shunt (TIPS) is a side-to-side portocaval shunt for threatening complications of portal hypertension. The purpose of this study was to evaluate in first 33 patients indicated for TIPS insertion in our institution the efficacy, complications, and mortality. Indication was failure of sclerotherapy or ligation in control either of acute (n = 4) or repetitive (n = 25) variceal bleeding and refractory ascites (n = 4). The technical success rate was with 70% (21/30) lower than expected, but the complication rate was also very low. There were no fatal complications, only one subcapsular liver hematome, and in one patient repetitive punction of biliary tract. The 30-days mortality was 10% (2/21) and rebleeding was 15% (3/20), caused always by thrombosis of the shunt. TIPS seems to be a promising therapeutic procedure after failed endoscopic therapy of esophageal varices without the mortality and morbidity of an open surgical procedure. Recent indications for TIPS are acute variceal hemorrhage refractory to endoscopic treatment and recurrent variceal bleeding despite sclerotherapy or band ligation. Promising seems to be TIPS insertion in the treatment of refractory ascites.     

Antibiotic phenol nor-triterpenes from Maytenus canariensis

OBJECTIVE: To calculate and compare the costs of the treatment of varicocele by antegrade scrotal sclerotherapy with other modalities. PATIENTS AND METHODS: A total of 2305 operations using antegrade scrotal sclerotherapy to treat varicocele in childhood and adolescence were analysed for cost factors and compared with different surgical treatment methods for varicocele. RESULTS: Calculation of the pre-, intra- and post-operative costs showed that antegrade scrotal sclerotherapy was the most economically effective of all forms of surgical management for varicocele. CONCLUSIONS: Because antegrade scrotal sclerotherapy is a cost-effective treatment for varicocele, the indications for treatment may be widened to include more men with potential infertility, and thus avoid the need for expensive methods of artificial fertilization.     

Terlipressin (glypressin) versus somatostatin in the treatment of bleeding esophageal varices--final report of a placebo-controlled, double-blind study

One hundred and six episodes of bleeding from esophageal or gastric varices in 72 patients with cirrhosis of the liver were randomized to treatment either with intravenous terlipressin 2 mg initially and 1 mg every four hours for 24 hours together with bolus injection and continuous infusion of placebo, or with somatostatin 250 micrograms as a bolus and continuous infusion of 250 micrograms/h somatostatin for 24 hours and placebo injections. Standard treatment with transfusions, fluid and electrolyte correction, and lactulose was administered in both groups. In the terlipressin group, 48 out of 53 bleeding episodes (91%) and in the somatostatin group 43 out of 53 bleeds (81%) were initially stopped by the vasoactive drugs. Four of the five bleeds not arrested by terlipressin, and nine of the ten bleeds not arrested by somatostatin, were stopped by balloon tamponade. In one patient in each group variceal bleeding could not be stopped initially, and both patients died. The failure rate of the vasoactive treatment alone, including rebleeds within the study period, was 17% in the terlipressin, and 28% in the somatostatin, group. The initial hemostasis, including balloon tamponade, were 98%, and the definitive bleeding control rates were 89% in both groups. The hospital mortality rate was 21% (11/53) in the terlipressin, and 21% (11/53) in the somatostatin, group. Blood transfusions and duration of bleeding did not differ significantly. The study indicates that a large proportion of bleeds from esophageal and fundic varices can be stopped initially (86%) and definitively controlled (77%) by vasoactive drugs alone.     

Our experience in the percutaneous treatment of varicocele

For its high incidence among young men and its affecting male fertility, varicocele requires an accurate screening, as well as an early and definitive treatment. The Authors report their experience in the treatment of varicocele with sclerotherapy: 24 patients underwent sclerotherapy of the left internal spermatic vein with a success rate of 91%. Complications never required hospitalization or surgery. Percutaneous therapy represents thus the treatment of choice in case of varicocele: compared with surgery, it offers similar clinical results and a lower recurrence rate, and it can be performed on an outpatient basis. Surgery should be performed only when anatomic variants make percutaneous treatment not feasible.     

Longterm outcome after injection sclerotherapy for oesophageal varices in children with extrahepatic portal hypertension

A consecutive series of 36 children with bleeding from oesophageal varices secondary to extrahepatic portal hypertension was successfully treated by endoscopic injection sclerotherapy and followed up over a mean period of 8.7 years after variceal obliteration. There were no deaths from portal hypertension or its treatment and morbidity related to oesophageal sclerotherapy was minimal. Endoscopic injection sclerotherapy alone proved safe and effective in controlling variceal bleeding from portal hypertension in over 80% of the children. Recurrent variceal bleeding developed in 10 (31%) patients but half of these were effectively treated by further sclerotherapy. Gastric variceal bleeding unresponsive to sclerotherapy necessitated successful portosystemic shunt surgery in four (13%) patients. Two children required splenectomy for painful splenomegaly. In most children injection sclerotherapy is the best treatment for the primary management of bleeding oesophageal varices, reserving portosystemic shunting or other surgical procedures for those with bleeding from gastrointestinal varices.     

Pathogenetic significance of increased levels of interleukin-8 in the peritoneal fluid of patients with endometriosis

BACKGROUND AND PURPOSE: The rationale behind early aneurysm surgery in patients with subarachnoid hemorrhage (SAH) is the prevention of rebleeding as early as possible after SAH. In addition, by clipping the aneurysm as early as possible, one can apply treatment for cerebral ischemia more vigorously (induced hypertension) without the risk of rebleeding. Hypervolemic hemodilution is now a well-accepted treatment for delayed cerebral ischemia. We compared the prospectively collected clinical data and outcome of patients admitted to the intensive care unit in the period 1977 to 1982 with those of patients admitted in the period 1989 to 1992 to measure the effect of the change in medical management procedures on patients admitted in our hospital with SAH. METHODS: We studied 348 patients admitted within 72 hours after aneurysmal SAH. Patients with negative angiography results and those in whom death appeared imminent on admission were excluded. The first group (group A) consisted of 176 consecutive patients admitted from 1977 through 1982. Maximum daily fluid intake was 1.5 to 2 L. Hyponatremia was treated with fluid restriction (<1 L/24 h). Antihypertensive treatment with diuretic agents was given if diastolic blood pressure was >110 mm Hg. Patients in the second group (172 consecutive patients; group B) were admitted from 1989 through 1992. Daily fluid intake was at least 3 L, unless cardiac failure occurred. Diuretic agents and antihypertensive medications were avoided. Cerebral ischemia was treated with vigorous plasma volume expansion under intermittent monitoring of pulmonary wedge pressure, cardiac output, and arterial blood pressure, aiming for a hematocrit of 0.29 to 0.33. Aneurysm surgery was planned for day 12. RESULTS: Patients admitted in group B had less favorable characteristics for the development of cerebral ischemia and for good outcome when compared with patients in group A. Despite this, we found a significant decrease in the frequency of delayed cerebral ischemia in patients of group B treated with tranexamic acid (P=0.00005 by log rank test) and significantly improved outcomes among patients with delayed cerebral ischemia (P=0.006 by chi2 test) and among patients with deterioration from hydrocephalus (P=0.001 by chi2 test). This resulted in a significant improvement of the overall outcome of patients in group B when compared with those in group A (P=0.006 by chi2 test). The major cause of death in group B was rebleeding (P=0.011 by chi2 test). CONCLUSIONS: We conclude that the outcome in our patients with aneurysmal SAH was improved but that rebleeding remains a major cause of death. Patient outcome can be further improved if we can increase the efficacy of preventive measures against rebleeding by performing early aneurysm surgery.