**6.2 Is dialysis indicated?**

When coming to the role of RRT in the management of adult patients with hyperammonemia, it is important to remember that data reporting the clinical outcomes of this intervention and supporting its usefulness are limited. One retrospective review of adult patients in the intensive care unit (ICU) with hyperammonemia not due to liver failure showed that the requirement of dialysis was not a predictor of mortality [5]. However, this retrospective study of a small sample size does not inform us when to start RRT for such patients. It is difficult to have well-established evidence-based guidelines for managing adult patients with this condition with the rarity and heterogeneous nature of available data. One guideline discussing the acute management of hyperammonemia patients suggested starting RRT for adult patients when the ammonia level exceeds 200 μmol/L [9]. Nevertheless, the level of evidence to support this recommendation was low, and most of the recommendations in this guideline were based on extrapolated data from pediatric patients [9]. However, this extrapolation is of limited value because of different patients' demographics, and different distribution of underlying causes of hyperammonemia. The following are the summaries of recommendations from different reports based on the authors' opinions:


*Role of RRT in Adult Patients with Hyperammonemia DOI: http://dx.doi.org/10.5772/intechopen.111997*

With the lack of strong evidence, and thus the lack of consensus recommendations, the decision about initiating RRT for adult patients with hyperammonemia needs to be individualized. This must take into consideration if other treatment modalities failed to lower ammonia levels or not, the presence of neurological consequences of hyperammonemia, and the ammonia level (more than 150 μmol/L). The role of RRT in some of the identifiable causes of hyperammonemia is discussed below.

#### **6.3 Continuous renal replacement therapy (CRRT) vs. intermittent hemodialysis**

If the decision was made to start renal replacement therapy for the management of hyperammonemia, the next decision to make is whether to start intermittent hemodialysis or CRRT. To decide about this, a few points must be remembered:


A scoping review of 28 studies looking at ammonia clearance by RRT in adult and pediatric patients concluded that intermittent hemodialysis provides the highest ammonia clearance followed by CRRT and, at very low levels, peritoneal dialysis [6]. In this review, clearance correlated with Qb and Qd in the case of intermittent hemodialysis, and with the effluent flow rate in CRRT [6].

Therefore, it might be prudent to start with conventional hemodialysis to ensure rapid reduction in ammonia level, followed by CRRT to prevent the rebound increase in ammonia level. However, this decision needs to be individualized and must take into consideration the advantage and disadvantages of each modality of RRT, the available resources, patient's condition, ammonia generation and metabolism in each specific case, and various organ functions (e.g., kidneys, liver, muscles, intestine, and brain) [11].

Of note: ammonia is osmotically active, yet, its rapid removal by dialysis is not associated with dialysis disequilibrium syndrome [18]. This is because the contribution of ammonia (even in the case of severe hyperammonemia) to plasma osmolality is negligible [17]. Additionally, the rapid equilibration of ammonia across the cell membrane will minimize any risk of dialysis disequilibrium syndrome.
