A randomized trial comparing terlipressin and noradrenaline in patients with cirrhosis and septic shock.

BACKGROUND & AIMS: The choice of vasopressor for treating cirrhosis with septic shock is unclear. While noradrenaline in general is the preferred vasopressor, terlipressin improves microcirculation in addition to vasopressor action in non-cirrhotics. We compared the efficacy and safety of noradrenaline and terlipressin in cirrhotics with septic shock. PATIENTS AND METHODS: Cirrhotics with septic shock underwent open label randomization to receive either terlipressin (n=42) or noradrenaline (n=42) infusion at a titrated dose. The primary outcome was mean arterial pressure (MAP) >65 mm Hg at 48 h. RESULTS: Baseline characteristics were comparable between the terlipressin and noradrenaline groups.SBP and pneumonia were major sources of sepsis. A higher proportion of patients on terlipressin were able to achieve MAP >65 mm of Hg (92.9% vs 69.1% P=.005) at 48 h. Subsequent discontinuation of vasopressor after hemodynamic stability was better with terlipressin (33.3% vs 11.9%, P<.05). Terlipressin compared to noradrenaline prevented variceal bleed (0% vs 9.5%, P=.01) and improved survival at 48 h (95.2% vs 71.4%, P=.003). Percentage lactate clearance (LC) is an independent predictor of survival [P=.0001, HR=3.9 (95% CI: 1.85-8.22)] after achieving the target MAP.Therapy related adverse effect were comparable in both the arms (40.5% vs 21.4%, P=.06), mostly minor (GradeII-88%) and reversible. CONCLUSIONS: Terlipressin is as effective as noradrenaline as a vasopressor in cirrhotics with septic shock and can serve as a useful drug. Terlipressin additionally provides early survival benefit and reduces the risk of variceal bleed. Lactate clearance is a better predictor of outcome even after achieving target MAP, suggesting the role of microcirculation in septic shock.

Interfacial transport of evaporating water confined in nanopores.

A semianalytical, continuum analysis of evaporation of water confined in a cylindrical nanopore is presented, wherein the combined effect of electrostatic interaction and van der Waals forces is taken into account. The equations governing fluid flow and heat transfer between liquid and vapor phases are partially integrated analytically, to yield a set of ordinary differential equations, which are solved numerically to determine the flow characteristics and effect on the resulting shape and rate of evaporation from the liquid-vapor interface. The analysis identifies three important parameters that significantly affect the overall performance of the system, namely, the capillary radius, pore-wall temperature, and the degree of saturation of vapor phase. The extension of meniscus is found to be prominent for smaller nanoscale capillaries, in turn yielding a greater net rate of evaporation per unit pore area. The effects of temperature and ambient vapor pressure on net rate of evaporation are shown to be analogous. An increase in pore-wall temperature, which enhances saturation pressure, or a decrease in the ambient vapor pressure result in enhancing the net potential for evaporation and increasing the curvature of the interface.

Nutritional status of patients with Crohn's disease.

BACKGROUND AND AIM: Malnutrition is a common feature in patients with Crohn's disease (CD), which leads to frequent infections and poor prognosis. In view of the rising incidence of CD in India we planned this study to assess the nutritional status of patients with CD. METHODS: Nutritional status of 112 patients (mean age 35.9 [SD 11.7] years; 61 men) with CD was assessed by anthropometric, dietary and biochemical parameters. Patients were considered malnourished if 3 or more anthropometric parameters (% ideal body weight [IBW], % tricep skin fold [TSF], %mid upper arm circumference [MUAC], and % mid arm muscle circumference [MAMC], body mass index [BMI]) were abnormal. Dietary intake was assessed by a 24-hour dietary recall along with a semi-quantitative food frequency method. Eighty volunteers were taken as healthy controls (HC). RESULTS: At the time of assessment, 77 patients were in remission and 35 had active disease. The values of BMI, MUAC, TSF and mid arm fat area (MAFA) in patients were significantly lower than those in healthy controls. MAMC and mid arm muscle area (MAMA) of patients and controls were comparable. TSF (Rem vs HC = 10.4 [2.8-71] vs 16 [3-41]) and MAFA (Rem vs HC = 1236 [240-7757] vs 1858 [322-5650]) of the patients in the remission phase were significantly lower than those of healthy controls; the remaining parameters were comparable. There was no difference in the dietary intake of patients in the remission and active phases, and healthy controls. The percentage energy fulfillment of the patients was lower than that of healthy controls. Twenty-nine of 35 (82.8%) patients in the active and 30 of 77 (38.9%) patients in the remission phase were malnourished (OR 7.5, 95% CI 2.8-20.4). The overall prevalence of malnutrition was 52.6% among patients. CONCLUSION: The percentage of malnourished patients in the active and remission phases of the disease was 82.8% and 38.9%, respectively, possibly due to low percentage energy fulfillment.

Intestinal permeability and its association with the patient and disease characteristics in Crohn's disease.

AIM: To assess the intestinal permeability (IP) in patients with Crohn's disease (CD) and study the association of IP with the patient and disease characteristics. METHODS: One hundred and twenty five consecutive patients of CD (Males: 66) were diagnosed on the basis of a combination of standard clinical, endoscopic, imaging and histological features. CD activity index (CDAI) was used to calculate the activity of the disease while the behavior of the disease was assessed by the modified Montreal classification. IP was measured by the ratio of the percentage excretion of ingested doses of lactulose and mannitol in urine (LMR). The upper limit of normality of LMR (0.037) was derived from 22 healthy controls. RESULTS: Thirty six percent of patients with CD had increased IP. There was no significant difference in mannitol excretion (patients vs controls=12.5% vs 14.2%, P=0.4652), but lactulose excretion was significantly higher in patients compared to healthy controls (patients vs controls=0.326% vs 0.293%, P=0.0391). The mean LMR was also significantly higher in the patients as compared to healthy controls [0.027 (0.0029-0.278) vs 0.0164 (0.0018-0.0548), P=0.0044]. Male patients had a higher LMR compared to females [0.036 (95% CI 0.029, 0.046) vs 0.022 (95% CI 0.0178, 0.028) (P=0.0024), though there was no difference in the number of patients with abnormal IP in both the sexes. Patients with an ileo-colonic disease had a higher LMR than those with only colonic disease [0.045 (95% CI 0.033, 0.06) vs 0.021 (95% CI 0.017, 0.025) (P<0.001)]. Of patients with ileo-colonic disease, 57.8% had an abnormal IP, compared to 26.7% with colonic and 15.6% with small intestinal disease. Patients with a stricturing disease had significantly higher LMR compared to non-fistulising non-stricturing disease [0.043 (95% CI 0.032, 0.058) vs 0.024 (95% CI 0.019, 0.029) (P=0.0062)]. There was no correlation of IP with age, disease activity, duration of illness, D-xylose absorption, upper GI involvement, perianal disease, and extra-intestinal manifestations. On multiple regression analysis, male gender and ileo-colonic disease were independent factors associated with increased IP. Gender, location, behavior of the disease and upper GI involvement could explain up to 23% of variability in IP (R2=0.23). CONCLUSION: IP was increased in 36% of patients with CD. Male gender and an ileo-colonic disease were the independent factors associated with increased IP.

Electrophysiological and neuropsychological tests for the diagnosis of subclinical hepatic encephalopathy and prediction of overt encephalopathy.

BACKGROUND: Subclinical hepatic encephalopathy (SHE) features in 30-84% of patients with cirrhosis of the liver. Its clinical significance with regards to progression to overt encephalopathy has however, not been established. AIMS: The present study was conducted (i) to compare the diagnostic usefulness of neuropsychological tests with that of electrophysiological (EP) tests in detection of SHE, and (ii) to examine the natural course of SHE. METHODS: Seventy-five-nonencephalopathic cirrhotics (11 females, 64 males; mean (+/- SD) age 43.6 (+/- 11.7) years; mean (+/- SD) education 11(+/- 3) years) were studied using a battery of tests for intelligence and memory, the number connection test (NCT), and EP tests viz. electroencephalogram (EEG) and auditory P300 event related potentials (P3ERP). All the patients were followed up for a period of 6 months to 2 years for development of overt encephalopathy. RESULTS: Thirty-five out of 75(47%) patients were diagnosed to have SHE based on at least one abnormal test result. The P3ERP latencies detected SHE in maximum number of patients (23%) followed by EEG (21%). Nearly 59% of patients with SHE progressed to overt encephalopathy within a mean duration of 4 months. Multivariate analysis showed that prior episode of encephalopathy (RR = 6.3; 95% CI = 2.0-19.7), abnormality on EEG (RR = 7.5; 95% CI = 2.2-25.3), abnormal performance on psychometric battery of tests (RR = 35.2; 95% CI = 4.3-287.3), occurrence of gastrointestinal bleed (RR = 19.3; 95% CI = 4.1-88.9), occurrence of dehydration (RR = 10.7; 95% CI = 2.5-45.4) and infection (RR = 11.4; 95% CI = 2.0-64.4) had significantly higher risk for development of overt encephalopathy. CONCLUSIONS: EP methods were more sensitive in detection of SHE. Amongst all the tests used, presence of only an abnormal EEG was significantly associated with development of overt encephalopathy along with the precipitating factors.