Non-interventional follow-up versus fluid bolus in RESPONSE to oliguria in hemodynamically stable critically ill patients: a randomized controlled pilot trial

Abstract

Background: Fluid bolus therapy is a common intervention to improve urine output. Data concerning the effect of a fluid bolus on oliguria originate mainly from observational studies and remain controversial regarding the actual benefit of such therapy. We compared the effect of a follow-up approach without fluid bolus to a 500 mL fluid bolus on urine output in hemodynamically stable critically ill patients with oliguria at least for 2 h (urine output < 0.5 mL/kg/h) in randomized setting.

Methods: We randomized 130 patients in 1:1 fashion to receive either (1) non-interventional follow-up (FU) for 2 h or (2) 500 mL crystalloid fluid bolus (FB) administered over 30 min. The primary outcome was the proportion of patients who doubled their urine output, defined as 2-h urine output post-randomization divided by urine output 2 h pre-randomization. The outcomes were adjusted for the stratification variables (presence of sepsis or AKI) using two-tailed regression. Obtained odds ratios were converted to risk ratios (RR) with 95% confidence intervals (CI). The between-group difference in the continuous variables was compared using mean or median regression and expressed with 95% CIs.

Results: Altogether 10 (15.9%) of 63 patients in the FU group and 22 (32.8%) of 67 patients in FB group doubled their urine output during the 2-h period, RR (95% CI) 0.49 (0.23-0.71), P = 0.026. Median [IQR] change in individual urine output 2 h post-randomization compared to 2 h pre-randomization was - 7 [- 19 to 17] mL in the FU group and 19[0-53] mL in the FB group, median difference (95% CI) - 23 (- 36 to - 10) mL, P = 0.001. Median [IQR] duration of oliguria in the FU group was 4 [2-8] h and in the FB group 2 [0-6] h, median difference (95%CI) 2 (0-4) h, P = 0.038. Median [IQR] cumulative fluid balance on study day was lower in the FU group compared to FB group, 678 [518-1029] mL versus 1071 [822-1505] mL, respectively, median difference (95%CI) - 387 (- 635 to - 213) mL, P < 0.001.

Conclusions: Follow-up approach to oliguria compared to administering a fluid bolus of 500 mL crystalloid in oliguric patients improved urine output less frequently but lead to lower cumulative fluid balance. Trial registration clinical.

Trials: gov, NCT02860572. Registered 9 August 2016.

Keywords: Acute kidney injury; Fluid balance; Fluid bolus; Oliguria; Sepsis.

Fig. 1

Flowchart. ^aChronic kidney disease (estimated precritical illness glomerular filtration rate < 60 mL/min/1.73 m²). ^bRenal replacement therapy (RRT) has been already started in the ICU for AKI, or commencing RRT (according to last laboratory values) was likely within the next 6 h or patient underwent regular (chronic) dialyses. ^cPatient has received less than 20 mL/kg i.v. fluids during the last 12 h for shock/hypovolemia or patient has been in the ICU less than 6 h. ^dCardiac arrhythmias affecting blood pressure, increase in norepinephrine need over 0.2 ug/kg/min, need for initiation of inotrope/inodilator within the last 2 h pre-randomization. ^eUrgent indications for commencing RRT for AKI at the moment of randomization were present (based on last blood work): plasma potassium > 6 mmol/L or severe metabolic acidosis (pH < 7.20 and bicarbonate < 12 mmol/L) or evidence of severe respiratory failure (PaO₂/FiO₂ ratio < 200) and clinical perception of volume overload or AKI has continued over 72 h. (Creatinine remains more than twice the normal level/oliguria continued.) ^fCumulative fluid accumulation exceeds 10% of baseline body weight. ^gBilateral infiltrates in chest X-ray. ^hObtaining informed written consent was not possible (i.e., patient or her/his next of kin did not speak Finnish or Swedish), or consent was denied. ^jFor example organ recipients, cardiopulmonary resuscitated patients with temperature control treatment, severe electrolyte disturbances (predominantly hyponatremia), logistic reasons, patients recruited in another study. Patient recruitment was interrupted in 2020 from March to May because of COVID-19 pandemic

Fig. 2

Administered fluids and urine output 6 h post-randomization according to intervention group. Bars represent median and whiskers interquartile range. *P < 0.05 and **P < 0.01, adjusted with sepsis and AKI; urine output did not differ from 3 h onward. Fluids in (mL) consisted of Ringer bolus (only in FB group), maintenance fluids, nutrition, medication, blood products, and possible rescue bolus. Fluid out (mL) consisted of urine output only. Period is expressed as hours

Fig. 3

a Mean arterial pressure, b central venous pressure, c heart rate, d norepinephrine dose, e capillary refill time and f arterial lactate from 0 to 6 h. The difference between FU and FB group was compared with linear mixed effect model. Values are means with SEM in figures (a, b, c and f). In figures d and e, values are geometric means with 95% Cis. *P < 0.05 and **P < 0.01 between groups on time points