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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

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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.

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Abbreviations

SAFE:

Saline versus Albumin Fluid Evaluation

MELD:

Model for end-stage liver disease

CTP:

Child-Pugh Score

MAP:

Mean arterial pressure

SOFA:

Sequential organ failure assessment

SIRS:

Systemic inflammatory response syndrome

OR:

Odds ratio

CI:

Confidence interval

KM:

Kaplan Meier

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Authors and Affiliations

  1. Department of Hepatology, Institute of Liver and Biliary Sciences, D-1, Vasant Kunj, New Delhi, 1100071, India

    Cyriac Abby Philips, Rakhi Maiwall, Manoj Kumar Sharma, Ankur Jindal, Ashok Kumar Choudhury & Shiv Kumar Sarin

  2. Department of Clinical Research and Biostatistics, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070, India

    Guresh Kumar, Ankit Bhardwaj & Shiv Kumar Sarin

  3. Department of Anesthesia and Critical Care, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi, 110070, India

    Lalita Gouri Mitra & Prashant Mohan Agarwal

Authors
  1. Cyriac Abby Philips
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  2. Rakhi Maiwall
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  3. Manoj Kumar Sharma
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  4. Ankur Jindal
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  5. Ashok Kumar Choudhury
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  10. Shiv Kumar Sarin
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Contributions

CAP and SKS conceived and designed the trial. CAP, SKS, RM were the chief investigators and oversaw the trial throughout. MKS, RM, AC, AJ were trial examiners. CAP, RM, AB, GK, LGM, VS, PMA monitored the data, did analyses, and provided critical feedback to study design and activities. All authors contributed to the interpretation of data, drafting of the report and decided on its content. All authors approved the final version.

Corresponding author

Correspondence to Shiv Kumar Sarin.

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Conflict of interest

The authors declare that they have none.

Ethical approval

This trial was approved by the Institutional Ethical Review Board and was done in accordance with the tenets of the Declaration of Helsinki. Written informed consent (presuming patients were unable to provide informed consent) was obtained from all of the respective participant’s family member before enrollment.

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Philips, C.A., Maiwall, R., Sharma, M.K. et al. 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. Hepatol Int 15, 983–994 (2021). https://doi.org/10.1007/s12072-021-10164-z

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  • DOI: https://doi.org/10.1007/s12072-021-10164-z

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