Maria A. Poca

Transfusion Strategies for Acute Upper Gastrointestinal Bleeding

BACKGROUND The hemoglobin threshold for transfusion of red cells in patients with acute gastrointestinal bleeding is controversial. We compared the efficacy and safety of a restrictive transfusion strategy with those of a liberal transfusion strategy. METHODS We enrolled 921 patients with severe acute upper gastrointestinal bleeding and randomly assigned 461 of them to a restrictive strategy (transfusion when the hemoglobin level fell below 7 g per deciliter) and 460 to a liberal strategy (transfusion when the hemoglobin fell below 9 g per deciliter). Randomization was stratified according to the presence or absence of liver cirrhosis. RESULTS A total of 225 patients assigned to the restrictive strategy (51%), as compared with 61 assigned to the liberal strategy (14%), did not receive transfusions (P<0.001) [corrected].The probability of survival at 6 weeks was higher in the restrictive-strategy group than in the liberal-strategy group (95% vs. 91%; hazard ratio for death with restrictive strategy, 0.55; 95% confidence interval [CI], 0.33 to 0.92; P=0.02). Further bleeding occurred in 10% of the patients in the restrictive-strategy group as compared with 16% of the patients in the liberal-strategy group (P=0.01), and adverse events occurred in 40% as compared with 48% (P=0.02). The probability of survival was slightly higher with the restrictive strategy than with the liberal strategy in the subgroup of patients who had bleeding associated with a peptic ulcer (hazard ratio, 0.70; 95% CI, 0.26 to 1.25) and was significantly higher in the subgroup of patients with cirrhosis and Child-Pugh class A or B disease (hazard ratio, 0.30; 95% CI, 0.11 to 0.85), but not in those with cirrhosis and Child-Pugh class C disease (hazard ratio, 1.04; 95% CI, 0.45 to 2.37). Within the first 5 days, the portal-pressure gradient increased significantly in patients assigned to the liberal strategy (P=0.03) but not in those assigned to the restrictive strategy. CONCLUSIONS As compared with a liberal transfusion strategy, a restrictive strategy significantly improved outcomes in patients with acute upper gastrointestinal bleeding. (Funded by Fundació Investigació Sant Pau; ClinicalTrials.gov number, NCT00414713.).

Consensus statement from the 2014 International Microdialysis Forum

Microdialysis enables the chemistry of the extracellular interstitial space to be monitored. Use of this technique in patients with acute brain injury has increased our understanding of the pathophysiology of several acute neurological disorders. In 2004, a consensus document on the clinical application of cerebral microdialysis was published. Since then, there have been significant advances in the clinical use of microdialysis in neurocritical care. The objective of this review is to report on the International Microdialysis Forum held in Cambridge, UK, in April 2014 and to produce a revised and updated consensus statement about its clinical use including technique, data interpretation, relationship with outcome, role in guiding therapy in neurocritical care and research applications.

Development of Ascites in Compensated Cirrhosis With Severe Portal Hypertension Treated With β-Blockers

OBJECTIVES:In compensated cirrhosis, a threshold value of hepatic venous pressure gradient (HVPG) ≥10 mm Hg is required for the development of decompensation. However, whether the treatment of portal hypertension (PHT) can prevent the transition into development of ascites once this level has been reached is unclear. Our aim was to assess the relationship between changes in HVPG induced by β-blockers and development of ascites in compensated cirrhosis with severe PHT.METHODS:Eighty-three patients without any previous decompensation of cirrhosis, with large esophageal varices and HVPG ≥12 mm Hg were included. After baseline hemodynamic measurements nadolol was administered and a second hemodynamic study was repeated 1–3 months later.RESULTS:During 53±30 months of follow-up, decompensation occurred in 52 patients (62%) and in 81% of them ascites was the first manifestation. Using receiver operating characteristic curve analysis a decrease in HVPG ≥10% was the best cutoff to predict ascites. As compared with nonresponders, patients with an HVPG decrease ≥10% had a lower probability of developing ascites (19% vs. 57% at 3 years, P<0.001), refractory ascites (P=0.007), and hepatorenal syndrome (P=0.027). By Cox regression analysis hemodynamic nonresponse was the best predictor of ascites. By stepwise logistic regression, development of ascites was independently associated with nonresponse, whereas refractory ascites, hepatorenal syndrome, and spontaneous bacterial peritonitis were not.CONCLUSIONS:In patients with compensated cirrhosis and large varices treated with β-blockers, an HVPG decrease ≥10% significantly reduces the risk of developing ascitic decompensation and other related complications such as refractory ascites or hepatorenal syndrome.

Terlipressin and albumin for type-1 hepatorenal syndrome associated with sepsis

BACKGROUND & AIMS Terlipressin and albumin is the standard of care for classical type-1 hepatorenal syndrome (HRS) not associated with active infections. However, there is no information on efficacy and safety of this treatment in patients with type-1 HRS associated with sepsis. Study aim was to investigate the effects of early treatment with terlipressin and albumin on circulatory and kidney function in patients with type-1 HRS and sepsis and assess factors predictive of response to therapy. METHODS Prospective study in 18 consecutive patients with type-1 HRS associated with sepsis. RESULTS Treatment was associated with marked improvement in arterial pressure and suppression of the high levels of plasma renin activity and norepinephrine. Response to therapy (serum creatinine <1.5mg/dl) was achieved in 12/18 patients (67%) and was associated with improved 3-month survival compared to patients without response. Non-responders had significantly lower baseline heart rate, poor liver function tests, slightly higher serum creatinine, and higher Child-Pugh and MELD scores compared to responders. Interestingly, non-responders had higher values of CLIF-SOFA score compared to responders (14±3 vs. 8±1, respectively p<0.001), indicating greater severity of acute-on-chronic liver failure (ACLF). A CLIF-SOFA score ⩾11 had 92% sensitivity and 100% specificity in predicting no response to therapy. No significant differences were observed between responders and non-responders in baseline urinary kidney biomarkers. Treatment was safe and no patient required withdrawal of terlipressin. CONCLUSIONS Early treatment with terlipressin and albumin in patients with type-1 HRS associated with sepsis is effective and safe. Patients with associated severe ACLF are unlikely to respond to treatment.

Neuropsychological Findings in Congenital and Acquired Childhood Hydrocephalus

Hydrocephalus is an increase in cerebrospinal fluid volume that can be caused by a variety of etiologies. The most common connatal and acquired causes of hydrocephalus are spina bifida, aqueduct stenosis, and preterm low birthweight infants with ventricular hemorrhage. In general, the literature suggests mild neuropsychological deficits associated with hydrocephalus, which are predominant in visuospatial and motor functions, and other nonlanguage skills. Although the precise nature of the neuropsychological deficits in hydrocephalus are not completely known, several factors such as etiology, raised intracranial pressure, ventricular size, and changes in gray and white matter tissue composition as well as shunt treatment complications have been shown to influence cognition. In fact, the presence of complications and other brain abnormalities in addition to hydrocephalus such as infections, trauma, intraventricular hemorrhage, low birthweight, and asphyxia are important determinants of the ultimate cognitive status, placing the child at a high risk of cognitive impairment.

Cognitive dysfunction in cirrhosis is associated with falls: a prospective study.

Falls are frequent among patients with debilitating disorders and can have a serious effect on health status. Mild cognitive disturbances associated with cirrhosis may increase the risk for falls. Identifying subjects at risk may allow the implementation of preventive measures. Our aim was to assess the predictive value of the Psychometric Hepatic Encephalopathy Score (PHES) in identifying patients likely to sustain falls. One hundred and twenty‐two outpatients with cirrhosis were assessed using the PHES and were followed at specified intervals. One third of them exhibited cognitive dysfunction (CD) according to the PHES (<−4). Seventeen of the forty‐two patients (40.4%) with CD had at least one fall during follow‐up. In comparison, only 5 of 80 (6.2%) without CD had falls (P < 0.001). Fractures occurred in 4 patients (9.5%) with CD, but in no patients without CD (P = 0.01). Patients with CD needed more healthcare (23.8% versus 2.5%; P < 0.001), more emergency room care (14.2% versus 2.5%; P = 0.02), and more hospitalization (9.5% versus 0%; P = 0.01) as a result of falls than patients without CD. Patients taking psychoactive treatment (n = 21) had a higher frequency of falls, and this was related to an abnormal PHES. In patients without psychoactive treatment (n = 101), the incidence of falls was 32.4% in patients with CD versus 7.5% in those without CD (P = 0.003). In the multivariate analysis, CD was the only independent predictive factor of falls (odds ratio, 10.2; 95% confidence interval, 3.4‐30.4; P < 0.001). The 1‐year probability of falling was 52.3% in patients with CD and 6.5% in those without (P < 0.001). Conclusion: An abnormal PHES identifies patients with cirrhosis who are at risk for falls. This psychometric test may be useful to promote awareness of falls and identify patients who may benefit from preventive strategies. (HEPATOLOGY 2012;55:1922–1930)

Development of hyperdynamic circulation and response to β-blockers in compensated cirrhosis with portal hypertension.

Nonselective β‐blockers are useful to prevent bleeding in patients with cirrhosis and large varices but not to prevent the development of varices in those with compensated cirrhosis and portal hypertension (PHT). This suggests that the evolutionary stage of PHT may influence the response to β‐blockers. To characterize the hemodynamic profile of each stage of PHT in compensated cirrhosis and the response to β‐blockers according to stage, we performed a prospective, multicenter (tertiary care setting), cross‐sectional study. Hepatic venous pressure gradient (HVPG) and systemic hemodynamic were measured in 273 patients with compensated cirrhosis before and after intravenous propranolol (0.15 mg/kg): 194 patients had an HVPG ≥10 mm Hg (clinically significant PHT [CSPH]), with either no varices (n = 80) or small varices (n = 114), and 79 had an HVPG >5 and <10 mm Hg (subclinical PHT). Patients with CSPH had higher liver stiffness (P < 0.001), worse Model for End‐Stage Liver Disease score (P < 0.001), more portosystemic collaterals (P = 0.01) and splenomegaly (P = 0.01) on ultrasound, and lower platelet count (P < 0.001) than those with subclinical PHT. Patients with CSPH had lower systemic vascular resistance (1336 ± 423 versus 1469 ± 335 dyne · s · cm‐5, P < 0.05) and higher cardiac index (3.3 ± 0.9 versus 2.8 ± 0.4 L/min/m2, P < 0.01). After propranolol, the HVPG decreased significantly in both groups, although the reduction was greater in those with CSPH (‐16 ± 12% versus ‐8 ± 9%, P < 0.01). The HVPG decreased ≥10% from baseline in 69% of patients with CSPH versus 35% with subclinical PHT (P < 0.001) and decreased ≥20% in 40% versus 13%, respectively (P = 0.001). Conclusion: Patients with subclinical PHT have less hyperdynamic circulation and significantly lower portal pressure reduction after acute β‐blockade than those with CSPH, suggesting that β‐blockers are more suitable to prevent decompensation of cirrhosis in patients with CSPH than in earlier stages. (Hepatology 2016;63:197–206)

Role of Albumin Treatment in Patients With Spontaneous Bacterial Peritonitis

BACKGROUND & AIMS Intravenous administration of albumin decreases the incidence of renal failure and mortality among patients with spontaneous bacterial peritonitis (SBP). However, it is unclear whether it should be given to all patients with SBP; we evaluated its efficacy. METHODS We analyzed data from all episodes of SBP (n = 216) during a 7-year period that occurred in a nonselected series of 167 patients with cirrhosis. Low-risk episodes (urea <11 mmol/L and bilirubin <68 μmol/L) were not treated with albumin, whereas high-risk episodes (urea >11 mmol/L and/or bilirubin >68 μmol/L) were or were not given albumin at the discretion of the attending physician. RESULTS Sixty-four episodes of SBP (29.6%) were low risk and not treated with albumin, whereas 152 (70.4%) were high risk; 73 of these (48%) were treated with albumin and 79 (52%) were not. Renal failure before SBP resolution was less frequent after low-risk episodes than high-risk episodes (4.7% versus 25.6%; P = .001), in-hospital mortality was lower (3.1% versus 38.2%; P < .001), and the 3-month probability of survival was higher (93% versus 53%; P < .001). In an analysis of only the high-risk group, patients who received albumin had lower in-hospital mortality than those not treated with albumin (28.8% versus 46.8%; P = .02) and a greater 3-month probability of survival (62% versus 45%; P = .01). CONCLUSIONS Albumin therapy increases survival of patients who have high-risk episodes of SBP, although it does not seem to be necessary for patients with low risk of death.

Functional and magnetic resonance imaging correlates of corpus callosum in normal pressure hydrocephalus before and after shunting

Background: Normal pressure hydrocephalus (NPH) is associated with corpus callosum abnormalities. Objectives: To study the clinical and neuropsychological effect of callosal thinning in 18 patients with idiopathic NPH and to investigate the postsurgical callosal changes in 14 patients. Methods: Global corpus callosum size and seven callosal subdivisions were measured. Neuropsychological assessment included an extensive battery assessing memory, psychomotor speed, visuospatial and frontal lobe functioning. Results: After surgery, patients showed improvements in memory, visuospatial and frontal lobe functions, and psychomotor speed. Two frontal corpus callosum areas, the genu and the rostral body, were the regions most related to the clinical and neuropsychological dysfunction. After surgery, total corpus callosum and four of the seven subdivisions presented a significant increase in size, which was related to poorer neuropsychological and clinical outcome. Conclusion: The postsurgical corpus callosum increase might be the result of decompression, re-expansion and increase of interstitial fluid, although it may also be caused by differences in shape due to cerebral reorganisation.

Influence of extraneurological insults on ventricular enlargement and neuropsychological functioning after moderate and severe traumatic brain injury

Extraneurological insults secondary to TBI such as hypotension or hypoxia have been associated with mortality and morbidity. The purpose of this study was to investigate the influence of systemic complications on both neuropsychological outcome and cerebral atrophy. Fifty-seven patients selected from 122 consecutive admissions were studied. Data on the type and severity of injury as well as other systemic insults were collected prior to and during the first 3 days of hospitalization. These data included the presence or absence of a hypoxic episode during the pre-hospital period, the presence and degree of hypoxia, hypercapnia, anemia, hypotension and intracranial hypertension, pupillary reactivity, Glasgow Coma Scale score and coma duration. From the last control CT scan image, performed 6 months post-injury, four different indexes of ventricular dilatation were calculated. Neuropsychological assessment at 6 months included tests of verbal and visual memory, visuoconstructive functions, fine motor speed, and frontal lobe functions. Our results showed that hypoxia and hypotension were related to neuropsychological outcome and long-term ventricular enlargement. Hypoxic episodes prior to hospitalization were related to third ventricle dilatation and to adverse neurological and cognitive outcomes, especially to attention, motor speed, mental flexibility, fluency and verbal memory impairments, suggesting fronto-striatal and hippocampal dysfunction. We conclude that the effect of extraneurological insults on brain structure and function may be as important as the severity of the primary injury.