Category: Critical Care
Posted: 7/16/2024 by Mark Sutherland, MD
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The CLOVERS trial (NEJM 2023) examined one of the eternal questions of critical care, liberal vs restrictive fluid management in sepsis… and found no difference. But there are criticism of CLOVERS, and while some other trials agreed with this result, there are also signals in the literature that restrictive fluid strategies are beneficial. Furthermore, we know that these trials suffer from issues of heterogeneity, and often lump together very different patients.
Jorda et al recently published in Critical Care a posthoc re-analysis of CLOVERS looking specifically at patients with advanced CKD (eGFR < 30). This is a challenging group of patients to manage. On the one hand their renal function is already marginal, so the last thing we want to do is potentially deprive starved kidneys of necessary intravascular volume, but on the flip side their septic shock puts them at high risk of full blown renal failure (transient or permanent) and they're thus at very high risk of fluid overload with aggressive resuscitative fluids and potentially limited ability to clear those fluids renally in the next few days. So how did these patients do in CLOVERS?
They did significantly better with the restrictive fluid strategy (mortality 22% vs 39%, HR CI 0.29-0.85). They also had more pressor free days and vent free days.
Bottom Line (my opinion): While a restrictive vs liberal fluid strategy in septic shock remains a bit up for debate, the evidence continues to slowly tip towards restrictive fluids (i.e. earlier pressors) as the preferred approach. In patients with advanced CKD (eGFR < 30), there is probably now sufficient evidence to favor vasopressors over IV fluid administration when resuscitating septic shock.
Jorda A, Douglas IS, Staudinger T, Heinz G, Bergmann F, Oberbauer R, Sengölge G, Zeitlinger M, Jilma B, Shapiro NI, Gelbenegger G. Fluid management for sepsis-induced hypotension in patients with advanced chronic kidney disease: a secondary analysis of the CLOVERS trial. Crit Care. 2024 Jul 11;28(1):231. doi: 10.1186/s13054-024-05019-6. PMID: 38992663; PMCID: PMC11238412.
National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network; Shapiro NI, Douglas IS, Brower RG, Brown SM, Exline MC, Ginde AA, Gong MN, Grissom CK, Hayden D, Hough CL, Huang W, Iwashyna TJ, Jones AE, Khan A, Lai P, Liu KD, Miller CD, Oldmixon K, Park PK, Rice TW, Ringwood N, Semler MW, Steingrub JS, Talmor D, Thompson BT, Yealy DM, Self WH. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension. N Engl J Med. 2023 Feb 9;388(6):499-510. doi: 10.1056/NEJMoa2212663. Epub 2023 Jan 21. PMID: 36688507; PMCID: PMC10685906.
