Extracorporeal Ammonia Clearance for Hyperammonemia in Critically Ill Patients: A Scoping Review

Abstract

<b><i>Introduction:</i></b> Hyperammonemia is a life-threatening condition. However, clearance of ammonia via extracorporeal treatment has not been systematically evaluated. <b><i>Methods:</i></b> We searched EMBASE and MEDLINE databases. We included all publications reporting ammonia clearance by extracorporeal treatment in adult and pediatric patients with clearance estimated by direct dialysate ammonia measurement or calculated by formula. Two reviewers screened and extracted data independently. <b><i>Results:</i></b> We found 1,770 articles with 312 appropriate for assessment and 28 studies meeting eligibility criteria. Most of the studies were case reports. Hyperammonemia was typically secondary to inborn errors of metabolisms in children and to liver failure in adult patients. Ammonia clearance was most commonly reported during continuous renal replacement therapy (CRRT) and appeared to vary markedly from <5 mL/min/m<sup>2</sup> to >250 mL/min/m<sup>2</sup>. When measured during intermittent hemodialysis (IHD), clearance was highest and correlated with blood flow rate (<i>R</i><sup>2</sup> = 0.853; <i>p</i> < 0.001). When measured during CRRT, ammonia clearance could be substantial and correlated with effluent flow rate (EFR; <i>R</i><sup>2</sup> = 0.584; <i>p</i> < 0.001). Neither correlated with ammonia reduction. Peritoneal dialysis (PD) achieved minimal clearance, and other extracorporeal techniques were rarely studied. <b><i>Conclusions:</i></b> Extracorporeal ammonia clearance varies widely with sometimes implausible values. Treatment modality, blood flow, and EFR, however, appear to affect such clearance with IHD achieving the highest values, PD achieving minimal values, and CRRT achieving substantial values especially at high EFRs. The role of other techniques remains unclear. These findings can help inform practice and future studies.

Clinical outcomes and prognostic factors of mortality in liver cirrhosis patients on continuous renal replacement therapy in two tertiary hospitals in Korea

“…We would expect to observe an improvement in mortality rate due to a reduction in complications from accumulated toxins caused by liver dysfunction. Consistent with this, several clinical studies have reported that CRRT can reduce serum bilirubin and ammonia levels [ 29 , 30 ]. However, literature regarding the relationship between bilirubin, ammonia excretion, and mortality is sparse.…”

Therapeutic plasma exchange in liver failure

“…Acute kidney injury requiring CRRT is a common manifestation of MOF in both ALF and ACLF[ 83 - 85 ]. In addition, CRRT is commonly utilized in patients with severe hyperammonemia to reduce the risk of ICH and cerebral edema[ 49 , 50 , 86 ]. CRRT is usually delivered over 24 h and the interruption of CRRT for TPE may compromise the duration of CRRT.…”

Ammonia Clearance with Different Continuous Renal Replacement Therapy Techniques in Patients with Liver Failure

“…Ammonia clearance in these studies varied considerably, often implausibly. However, higher blood and dialysate flow rates were consistently correlated with greater ammonia clearance, i.e., higher effluent rate and dose appeared to increase clearance [18]. Accordingly, we did not find any difference in clearance comparing CRRT techniques, where the dose by effluent rate per hour was the same.…”

“…To our knowledge, this is the first study to directly compare ammonia clearance between different CRRT techniques. There are limited studies investigating the extracorporeal clearance of ammonia in the critically ill. A recent review found only 13 published papers on this topic [18]. The largest body of research to date has occurred in the paediatric field, where both intermittent haemodialysis and CRRT have been used successfully to treat hyperammonaemia [19][20][21].…”