How fluid is too much ?
Rivers et al in 2001 had shown that Early Goal Directed Therapy (EGDT) provided significant benefits with respect to outcome in patients with severe sepsis and septic shock. Use EGDT resulted use of large volume of fluids and PRBC for resuscitation. Since then multiple studies has tested the validity of EGDT against usual care notably ARISE, ProcESS and ProMISE Trial. All the study failed to show any mortality benefits of EGDT compared to usual or standard care. Surviving Sepsis Guidelines (SSG 2021) suggest using 30ml/kg based on the fact that average amount of fluid received in all these trials pre randomisation was in the range of 30ml/kg.
To further analyse the use of restrictive and liberal fluids two other recent trials were done. CLOVERS Trial (2023) was done to asses early restrictive or liberal fluid management for sepsis induced hypotension which is better. Patients where randomly assigned to restrictive (782)and liberal fluid(781) strategy for 24 hours. They randomised the patients who met criteria for sepsis induced hypotension refractor to initial treatment with 1 to 3L of IV fluid. Study found that patients in restrictive fluid strategy had to use early, prevalent and longer duration of vasopressors. Study concluded that in patients with sepsis induced hypotension, the restrictive fluid strategy (14%) didnot lower the mortality at 90 days compared to liberal fluid strategy (14.9%) p=0.61.
CLASSIC Trial (2022) was done to study long term outcomes of restrictive versus standard intravenous IV fluid therapy in adult critically ill patients with septic shock. A total of 1549 patients where enrolled in the study 767 to restrictive group and 782 to standard fluid group. Study found that one year mortality was (51.3%) among restrictive group compared to standard fluid group (49.9%) p =0.55. Study concluded that restrictive v/s standard therapy resulted in similar survival, health related quality of life and cognitive function at 1 year.
SSG 2021 suggests use of crystalloid fluid at 30ml/kg IV within first 3 hours of resuscitation. Further resuscitation of the patients should be decided based on the intravascular status and organ perfusion. Dynamic measures including passive leg raising combined with cardiac output measurement (CO), fluid challenge against stroke volume, systolic pressure or pulse pressure.
In a resource limited setting a increase of pulse pressure by 15% following passive leg raising test for 60-90 seconds could indicate fluid responsiveness.
Reference
- Meyhoff TS, Hjortrup PB, Wetterslev J, Sivapalan P, Laake JH, Cronhjort M, Jakob SM, Cecconi M, Nalos M, Ostermann M, Malbrain M, Pettilä V, Møller MH, Kjær MN, Lange T, Overgaard-Steensen C, Brand BA, Winther-Olesen M, White JO, Quist L, Westergaard B, Jonsson AB, Hjortsø CJS, Meier N, Jensen TS, Engstrøm J, Nebrich L, Andersen-Ranberg NC, Jensen JV, Joseph NA, Poulsen LM, Herløv LS, Sølling CG, Pedersen SK, Knudsen KK, Straarup TS, Vang ML, Bundgaard H, Rasmussen BS, Aagaard SR, Hildebrandt T, Russell L, Bestle MH, Schønemann-Lund M, Brøchner AC, Elvander CF, Hoffmann SKL, Rasmussen ML, Martin YK, Friberg FF, Seter H, Aslam TN, Ådnøy S, Seidel P, Strand K, Johnstad B, Joelsson-Alm E, Christensen J, Ahlstedt C, Pfortmueller CA, Siegemund M, Greco M, Raděj J, Kříž M, Gould DW, Rowan KM, Mouncey PR, Perner A; CLASSIC Trial Group. Restriction of Intravenous Fluid in ICU Patients with Septic Shock. N Engl J Med. 2022 Jun 30;386(26):2459-2470. doi: 10.1056/NEJMoa2202707. Epub 2022 Jun 17. PMID: 35709019.
- 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.
- Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021
