1.
A randomized-controlled trial comparing 20% albumin to plasmalyte in patients with cirrhosis and sepsis-induced hypotension [ALPS trial]
Maiwall R, Kumar A, Pasupuleti SSR, Hidam AK, Tevethia H, Kumar G, Sahney A, Mitra LG, Sarin SK
Journal of hepatology. 2022
Abstract
BACKGROUND AND AIM The choice of resuscitation fluid in cirrhosis patients with sepsis-induced hypotension (SIH) is unclear. 5% albumin has been superior to normal saline in the FRISC study. We compared the efficacy and safety of 20% albumin, which has greater oncotic properties with plasmalyte in reversing SIH. METHODS Critically-ill cirrhosis(CIC) patients underwent open-label randomization to receive either 20% albumin [0.5-1.0gm/kg over 3 hours; n=50] or plasmalyte (30ml/kg over 3 hours, n=50). The primary end-point of the study was the attainment of mean arterial pressure (MAP) above 65 mmHg at three hours. RESULTS Baseline characteristics were comparable in albumin and plasmalyte groups; arterial lactate(mmol/L) [6.16±3.18 vs. 6.38±4.77; p=0.78), MAP (mmHg) [51.4±6.52 vs. 49.9±4.45; p=0.17] and SOFA score [10.8±2.96 vs. 11.1±4.2; p=0.68] respectively. Most patients were alcoholics (39%) and had pneumonia (40%). In the intention-to-treat (ITT) analysis, albumin was superior to plasmalyte in achieving the primary end-point (62% vs. 22%; p<0.001). A rapid decline in arterial lactate (P=0.03), a lesser proportion of dialysis [48% vs. 62%; p=0.16], and a higher time to initiation of dialysis (in hours) [68.13±47.79 vs. 99.7± 63.4; p=0.06] was seen with albumin. However, the 28-day mortality was not different (58% vs. 62%, p=0.57). Patients in the albumin group required discontinuation of therapy in 11 (22%) patients due to adverse effects compared to none in plasmalyte group. CONCLUSION In patients with cirrhosis and SIH, 20% albumin transiently improves the hemodynamics with early lactate clearance than plasmalyte but needs monitoring as it is more often attended with pulmonary complications. Both fluids provide comparable 28 days survival. NCT02721238 LAY SUMMARY The current randomized controlled trial performed in critically ill patients with cirrhosis and sepsis-induced hypotension highlights that 20% albumin restores hemodynamics but causes more pulmonary complications than plasmalyte. The impact on renal functions was also modest. These effects did not result in improvement in deaths at 28-days. Plasmalyte is safer and well-tolerated and can be considered for volume resuscitation in patients with cirrhosis and sepsis-induced hypotension.
2.
Comparison of 5% human albumin and normal saline for fluid resuscitation in sepsis induced hypotension among patients with cirrhosis (FRISC study): a randomized controlled trial
Philips CA, Maiwall R, Sharma MK, Jindal A, Choudhury AK, Kumar G, Bhardwaj A, Mitra LG, Agarwal PM, Sarin SK
Hepatology international. 2021
Abstract
AIMS: Sepsis and septic shock are common causes of hospitalization and mortality in patients with cirrhosis. There is no data on the choice of fluid and resuscitation protocols in sepsis-induced hypotension in cirrhosis. METHODS In this open-label trial conducted at a single center, we enrolled 308 cirrhotics with sepsis-induced hypotension and randomized them to receive either 5% albumin or normal saline. The primary endpoint was a reversal of hypotension [mean arterial pressure, MAP, ≥ 65 mmHg] at 3 h. Secondary endpoints included serial effects on heart rate, arterial lactate and urine output. RESULTS 154 patients each received 5% albumin (males, 79.8%, mean MAP 52.9 ± 7.0 mm Hg) or 0.9% saline (85.1%, 53.4 ± 6.3 mm Hg) with comparable baseline parameters and liver disease severity. Reversal of hypotension was higher in patients receiving 5% albumin than saline at the end of one hour [25.3% and 11.7%, p = 0.03, Odds ratio (95% CI)-1.9 (1.08-3.42)] and at the end of three hours [11.7% and 3.2%, p = 0.008, 3.9 (1.42-10.9)]. Sustained reduction in heart rate and hyperlactatemia (p < 0.001) was better in the albumin group. At one week, the proportion of patients surviving was higher in the albumin group than those receiving saline (43.5% vs 38.3%, p = 0.03). Female gender and SOFA ≥ 11 were predictors of non-response to fluid. CONCLUSIONS 5% human albumin is safe and beneficial in reversing sepsis-induced hypotension compared to normal saline in patients with cirrhosis improving clinically assessable parameters of systemic hemodynamics, tissue perfusion and in-hospital short-term survival of cirrhosis patients with sepsis.
3.
A randomized trial comparing terlipressin and noradrenaline in patients with cirrhosis and septic shock
Choudhury A, Kumar Kedarisetty C, Vashishtha C, Saini D, Kumar S, Maiwall R, Kumar Sharma M, Bhadoria AS, Kumar G, Joshi YK, et al
Liver International : Official Journal of the International Association for the Study of the Liver. 2016;37((4):):552-561.
Abstract
BACKGROUND AND 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 wasmean arterial pressure (MAP)>65mmHg at 48hours. RESULTS aseline characteristics were comparable between the terlipressin and noradrenaline groups.SBPand pneumoniawere major sources of sepsis. A higher proportion of patients on terlipressin wereable to achieve MAP >65mm of Hg (92.9% vs. 69.1% p=0.005) at 48hours. Subsequent discontinuation of vasopressor after hemodynamic stability was better with terlipressin(33.3%vs.11.9%, P<0.05). Terlipressin compared to noradrenaline prevented variceal bleed (0%vs.9.5%, P=0.01) and improved survival at 48 hours(95.2%vs.71.4%, P=0.003). Percentage lactate clearance (LC) is an independent predictor of survival [p=0.0001, HR= 3.9(95CI 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=0.06), mostly minor (GradeII-88%)andreversible. 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, reduces risk of variceal bleed. Lactate clearance is abetter predictor of outcome even after achieving target MAP- suggesting the role of microcirculation in septic shock. This article is protected by copyright. All rights reserved.