Acute Kidney Injury, Critical Illness, Fluid Overload
Conditions
Keywords
ICU, Intensive, CRRT, Fluid Removal, AKI, Critical Care
Brief summary
The objective of this pilot trial is to assess the feasibility of forced fluid removal in patients admitted to the intensive care unit (ICU) with high-risk AKI and severe fluid overload. The intervention will use furosemide infusion and/or continuous renal replacement therapy (CRRT) to achieve and maintain a neutral cumulative fluid balance. The intervention will be compared to standard of care as reflected in the kidney disease improving global outcome (KDIGO) guidelines.
Detailed description
Acute kidney injury (AKI) is a common and serious complication in patients admitted to ICU. A core element of critical care is resuscitation with crystalloid solutions. In many cases fluid accumulates and patients become fluid overloaded (positive fluid balance \> 10% of bodyweight). This is especially true in patients with AKI, since they often have impaired ability to excrete salt and water. Most observational suggests harm with increased positive fluid balance. Objectives: To assess feasibility of forced fluid removal with diuretics and/or CRRT in ICU patients with AKI and severe fluid overload, compared to current clinical practice. Design: Multicentre, parallel group, randomized, assessor blinded pilot-trial with adequate generation of allocation sequence, and allocation concealment. Trial Size: The pilot study is planned to include 50 patients. Inclusion is expected to start in August 2015.
Interventions
DRUGFurosemide (Furix)
* Loading dose: 40 mg I.V. * Infusion rate 40 mg/h * Continued until neutral cumulative fluid balance is achieved (the overall treatment goal) or average negative fluid balance is below 1 ml/kg/h for 8 hours.
OTHERContinuous renal replacement therapy (CRRT)
* Initiated in case of contraindications or inadequate effect of furosemide. * Fluid removal is started at 2 ml/kg/h * The efficacy is evaluated 3 times daily and removal rate increased by 0.5 ml/kg/h if the therapeutic goal is not achieved
OTHERResuscitation
The physiologic response to fluid removal is monitored with three variables indicating inadequate circulation. These are: * Mottling beyond the edge of kneecaps * Hypotension (MAP \< 50) resistant to inotropes and vasopressors * Plasma lactate ≥ 4 mmol/l Mottling and MAP are monitored continuously and lactate is measured routinely 4-6 times each day and on clinical indication. If one or more variable is present: 1. Fluid removal is paused 2. A crystalloid fluid bolus of 250-500 ml is given 3. Circulatory status is reevaluated within 30 minutes 4. Step 1-3 is repeated until signs of inadequate circulation have been resolved for minimum 1 hour 5. Fluid removal is restarted in 25% reduced dose for minimum 4 hours before evaluation of effect.
OTHERUsual Care
All interventions are performed at the discretion of the treating physician apart from initiation of renal replacement therapy which is discouraged unless one or more of the following criteria are met: * Hyperkalaemia (p-K+ \> 6 mmol/l) * Severe metabolic acidosis attributable to AKI (pH \< 7.25 and standard base excess \< -10 mmol/l) resistant to IV bicarbonate infusion * Severe respiratory failure with PaO2/FiO2 \< 13 kPa and bilateral infiltrates/oedema on the chest x-ray. * Progressive azotaemia and a blood urea nitrogen (BUN) \> 25 mmol/l.
Sponsors
Rigshospitalet, Denmark
Aalborg University Hospital
Nordsjaellands Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years of age * Acute Kidney Injury defined according to the KDIGO criteria * Renal Recovery Score ≤ 60%. (Calculated using www.renal-recovery-score.com) * Fluid overload defined as a positive fluid balance ≥ 10% of ideal body weight. * Able to undergo randomization within 12 hours of fulfilling other inclusion criteria
Exclusion criteria
* Known pre-hospitalization advanced chronic kidney disease. (eGFR \< 30 mL/minute/1.73 m2 or chronic RRT.) * Severe hypoxic respiratory failure (use of invasive ventilation and FiO2 \> 80% and PEEP \> 10 cm H2O) * Severe burn injury (≥ 10% TBSA) * Severe hypo- or hyper- natremia (\< 120 or \> 155 mmol/l) * Hepatic coma * Mentally disabled undergoing forced treatment * Pregnancy/breast feeding * Lack of commitment for on-going life support including RRT * Lack of informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative fluid balance | 5 days | Calculated as the sum of daily intake - daily output, as registered on the daily ICU observation charts. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative fluid balance | ICU stay expected average of 10 days | participants will be followed for the duration of ICU stay, an expected average of 10 days |
| Mean daily fluid balance | ICU stay expected average of 10 days | participants will be followed for the duration of ICU stay, an expected average of 10 days |
| Major protocol violations | ICU stay expected average of 10 days | participants will be followed for the duration of ICU stay, an expected average of 10 days |
| Time to neutral cumulative fluid balance | 90 days | No. of days until neutral cumulative fluid balance is achieved. Participants will be followed until neutral fluid balance is achieved or they reach the end of the observation period (90 days) |
| Accumulated serious adverse reactions | 90 days | Serious adverse reactions related to fluid removal(atrial fibrillation, ischemic events and organ failure), furosemide (severe electrolyte disturbance, severe thrombocytopenia, hearing loss agranulocytosis and allergic reactions) and the infusion of noradrenaline (cerebral hemorrhage, cardiac arrhythmia, psychiatric symptoms) will be examined |
Other
| Measure | Time frame | Description |
|---|---|---|
| Days alive and out of hospital | 90 days | — |
| Days alive and out of mechanical ventilation | 90 days | — |
| Days alive and out of renal replacement therapy | 90 days | — |
| Renal recovery | 90 days | Defined as 5 consecutive days of: * No renal replacement therapy * serum creatinine ≤ 150 % baseline value |
| All cause mortality | 90 days | — |
Countries
Denmark
Outcome results
None listed