Noninterventional follow-up vs fluid bolus in RESPONSE to oliguria-The RESPONSE trial protocol and statistical analysis plan

Nina Inkinen, Tuomas Selander, Ville Pettilä, Miia Valkonen, Minna Bäcklund, Johanna Wennervirta, Anni Pulkkinen, Johanna Hästbacka, Suvi T Vaara, Nina Inkinen, Tuomas Selander, Ville Pettilä, Miia Valkonen, Minna Bäcklund, Johanna Wennervirta, Anni Pulkkinen, Johanna Hästbacka, Suvi T Vaara

Abstract

Background: Oliguria is a frequent trigger for administering a fluid bolus, but the effect of fluid bolus in improving urine output is inadequately demonstrated. Here, we summarize the protocol and detailed statistical analysis plan of the randomized, controlled RESPONSE trial comparing follow-up as the experimental group and a 500 mL crystalloid fluid bolus as the control group for oliguria in critically ill oliguric patients.

Methods: Our trial is an investigator-initiated, randomized, controlled, pilot trial conducted in three ICUs in two centers. We aim to randomize 1:1 altogether 130 hemodynamically stable oliguric patients either to a 2-hour follow-up without interventions or to receive a crystalloid bolus of 500 mL over 30 minutes. The primary outcome is the change in individual urine output during the 2-hour period compared to 2 hours preceding randomization. Doubling of the urine output is considered clinically significant. Additionally, we record the duration of oliguria, physiological and biochemical variables, adverse events, and the incidences of acute kidney injury and renal replacement therapy.

Conclusions: Oliguria is a frequent trigger for potentially harmful fluid loading. Therefore, the RESPONSE trial will give information of the potential effect of fluid bolus on oliguria in critically ill patients.

Trial registration: clinical.trials.gov, NCT02860572.

Keywords: acute kidney injury; critically ill; fluid bolus; oliguria.

Conflict of interest statement

The authors report no conflicts of interest.

© 2020 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

Figures

Figure 1
Figure 1
Schematic presentation of determination of urine output for the primary endpoint variable. UO, urine output

References

    1. Glassford NJ, Eastwood GM, Bellomo R. Physiological changes after fluid bolus therapy in sepsis: a systematic review of contemporary data. Crit Care. 2014;18:696.
    1. Cecconi M, Hofer C, Teboul J‐L, et al. Fluid challenges in intensive care: the FENICE study: a global inception cohort study. Intensive Care Med. 2015;41:1529‐1537.
    1. Hoste EA, Maitland K, Brudney CS, et al. Four phases of intravenous fluid therapy: a conceptual model. Br J Anaesth. 2014;113:740‐747.
    1. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group . KDIGO clinical practice guideline for acute kidney injury. Kidney Int. 2012:1‐138.
    1. Lammi MR, Aiello B, Burg GT, et al. Response to fluid boluses in the fluid and catheter treatment trial. Chest. 2015;148(4):919‐926.
    1. Bihari S, Prakash S, Bersten AD. Post resusicitation fluid boluses in severe sepsis or septic shock: prevalence and efficacy (price study). Shock (Augusta, Ga). 2013;40:28‐34.
    1. Moussa MD, Scolletta S, Fagnoul D, et al. Effects of fluid administration on renal perfusion in critically ill patients. Crit Care. 2015;19:250.
    1. Prowle JR, Molan MP, Hornsey E, Bellomo R. Measurement of renal blood flow by phase‐contrast magnetic resonance imaging during septic acute kidney injury: a pilot investigation. Crit Care Med. 2012;40:1768‐1776.
    1. Prowle JR, Ishikawa K, May CN, Bellomo R. Renal plasma flow and glomerular filtration rate during acute kidney injury in man. Ren Fail. 2010;32:349‐355.
    1. Legrand M, Le Cam B, Perbet S, et al. Urine sodium concentration to predict fluid responsiveness in oliguric ICU patients: a prospective multicenter observational study. Crit Care. 2016;20:165.
    1. Aya HD, Ster IC, Fletcher N, Grounds RM, Rhodes A, Cecconi M. Pharmacodynamic analysis of a fluid challenge. Crit Care Med. 2016;44:880‐891.
    1. Nunes TS, Ladeira RT, Bafi AT, de Azevedo LC, Machado FR, Freitas FG. Duration of hemodynamic effects of crystalloids in patients with circulatory shock after initial resuscitation. Ann Intensive Care. 2014;4:25.
    1. Bouchard J, Soroko SB, Chertow GM, et al. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int. 2009;76:422‐427.
    1. Vaara ST, Korhonen A‐M, Kaukonen K‐M, et al. Fluid overload is associated with an increased risk for 90‐day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study. Crit Care. 2012;16:R197.
    1. Garzotto F, Ostermann M, Martín‐Langerwerf D, et al. The dose response multicentre investigation on fluid assessment (DoReMIFA) in critically ill patients. Crit Care. 2016;20:196.
    1. Renal T. An observational study fluid balance and patient outcomes in the randomized evaluation of normal vs. augmented level of replacement therapy trial*. Crit Care Med. 2012;40:1753‐1760.
    1. Chan A‐W, Tetzlaff JM, Altman DG, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158:200‐207.
    1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis‐3). JAMA. 2016;315:801‐810.
    1. Poukkanen M, Wilkman E, Vaara ST, et al. Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study. Crit Care. 2013;17:R295.
    1. Silbert BI, Ho KM, Lipman J, et al. Determinants of urinary output response to IV furosemide in acute kidney injury: a pharmacokinetic/pharmacodynamic study. Crit Care Med. 2016;44(10):e923‐e929.
    1. Glassford NJ, Mårtensson J, Eastwood GM, et al. Defining the characteristics and expectations of fluid bolus therapy: a worldwide perspective. J Crit Care. 2016;35:126‐132.
    1. Ukor IF, Hilton AK, Bailey MJ, Bellomo R. The haemodynamic effects of bolus versus slower infusion of intravenous crystalloid in healthy volunteers. J Crit Care. 2017;41:254‐259.
    1. Bihari S, Wiersema UF, Schembri D, et al. Bolus intravenous 0.9% saline, but not 4% albumin or 5% glucose, causes interstitial pulmonary edema in healthy subjects. J Appl Physiol. 1985;2015(119):783‐792.
    1. Chawla LS, Davison DL, Brasha‐Mitchell E, et al. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013;17:R207.
    1. Kahan BC, Morris TP. Reporting and analysis of trials using stratified randomisation in leading medical journals: review and reanalysis. BMJ. 2012;345:e5840.
    1. Gomez H, Ince C, De Backer D, et al. A unified theory of sepsis‐induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock. 2014;41:3‐11.
    1. Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Ann Intern Med. 2010;152:726‐732.
    1. Meyhoff TS, Hjortrup PB, Møller MH, et al. Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial‐protocol and statistical analysis plan. Acta Anaesthesiol Scand. 2019;63:1262‐1271.
    1. Self WH, Semler MW, Bellomo R, et al. Liberal versus restrictive intravenous fluid therapy for early septic shock: rationale for a randomized trial. Ann Emerg Med. 2018;72:457‐466.
    1. Prowle JR, Kirwan CJ, Bellomo R. Fluid management for the prevention and attenuation of acute kidney injury. Nat Rev Nephrol. 2014;10:37‐47.
    1. Ostermann M, Liu K, Kashani K. Fluid management in acute kidney injury. Chest. 2019;156:594‐603.

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