Cerebral microembolism in the critically ill with acute kidney injury (COMET-AKI trial): study protocol for a randomized controlled clinical trial

Abstract

Background: Microembolism is a frequent pathological event during extracorporeal renal replacement therapy (RRT). Some previous data indicate that microemboli are generated in patients who are undergoing RRT and that these may contribute to increased cerebrovascular and neurocognitive morbidity in patients with end-stage renal disease. The current trial aims to quantify the microembolic load and respective qualitative composition that effectively reaches the intracerebral circulation in critically ill patients treated with different RRT modalities for acute kidney injury (AKI).

Methods/design: The COMET-AKI trial is a prospective, randomized controlled clinical trial with a 2-day clinical assessment period and follow-up visits at 6 and 12 months. Consecutive critically ill patients with AKI on continuous renal replacement therapy (CRRT) scheduled for a switch to intermittent renal replacement therapy (IRRT) will be randomized to either switch to IRRT within the next 24 h or continued CRRT for an additional 24 h. Cerebral microembolic load will be determined at baseline, i.e., before switch (on CRRT for both groups) and on IRRT versus CRRT, whichever group they were randomized to. The primary endpoint is defined as the difference in mean total cerebral microemboli count during the measurement period on CRRT versus IRRT following randomization. Microemboli will be assessed within the RRT circuit by a 1.5-MHz ultrasound detector attached to the venous RRT tubing and cerebral microemboli will be measured in the middle cerebral artery using a 1.6-MHz robotic transcranial Doppler system with automatic classification of Doppler signals as solid or gaseous. In addition to Doppler measurements, patients will be examined by magnetic resonance imaging and neurocognitive tests to gain better understanding into the potential morphological and clinical consequences of embolization.

Discussion: The results of COMET-AKI may help to gain a better insight into RRT modality-associated differences regarding microbubble generation and the cerebral microembolic burden endured by RRT recipients. Furthermore, identification of covariates of microbubble formation and distribution may help to encourage the evolution of next-generation RRT circuits including machinery and/or filters.

Trial registration: ClinicalTrials.gov, ID: NCT02621749 . Registered on 3 December 2015.

Keywords: Acute kidney injury; Cerebral microembolism; Critically ill patients; Renal replacement therapy.

Fig. 1

Patient flow diagram with allocation to CRRT versus IRRT. CRRT continuous renal replacement therapy, IRRT intermittent renal replacement therapy, RRT renal replacement therapy, TTE transthoracic echocardiography examination, TEE transesophageal echocardiography examination, TCD transcranial Doppler ultrasound, MRI magnetic resonance imaging, CAM-ICU Confusion Assessment Method for the Intensive Care Unit, RASS Richmond Agitation and Sedation Scale, MoCA Montreal Cognitive Assessment, MCA middle cerebral artery, SF-36 Short Form (36) Health Survey

Fig. 2

Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Figure: schedule of enrollment, interventions and assessments for the COMET-AKI trial. CRRT continuous renal replacement therapy, IRRT intermittent renal replacement therapy, TTE transthoracic echocardiography examination, TEE transesophageal echocardiography examination, TCD transcranial Doppler ultrasound, MRI magnetic resonance imaging, CAM-ICU Confusion Assessment Method for the Intensive Care Unit, RASS Richmond Agitation and Sedation Scale, MoCA Montreal Cognitive Assessment, MCA middle cerebral artery, SF-36 Short Form (36) Health Survey