From the Guidelines
The most recommended initial treatment for hyperammonemia is high-dose continuous kidney replacement therapy (CKRT) with a blood flow rate (Qb) of 30-50 ml/min and a dialysate flow rate (Qd)/Qb >1.5, which enables rapid clearance of ammonia and reduces the need to switch between hemodialysis (HD) and CKRT modalities. This recommendation is based on the consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy 1.
The guidelines suggest that CKRT should be initiated in patients with hyperammonaemia in the following situations: rapidly deteriorating neurological status, coma, or cerebral oedema with blood ammonia level >150 μmol/l; presence of either moderate or severe encephalopathy; persistently high blood ammonia levels >400 μmol/l refractory to non-kidney replacement therapy (NKRt) medical measures; and rapid rise in blood ammonia levels to >300 μmol/l within a few hours that cannot be controlled via NKRt medical therapies 1.
In addition to CKRT, supportive care is essential, including fluid management, correction of electrolyte imbalances, and prevention of catabolism through adequate caloric intake. Protein intake should be temporarily restricted while maintaining positive nitrogen balance. The use of nitrogen-scavenging agents, such as sodium benzoate and sodium phenylacetate, may also be considered in conjunction with CKRT or HD 1.
It is worth noting that intermittent HD can also be effective in rapidly reducing ammonia levels, especially in patients with rapidly deteriorating neurological status, coma, or cerebral oedema 1. However, the risk of rebound hyperammonaemia and the need for repeated HD sessions may limit its use. Hybrid therapy, which combines HD and CKRT, may also be considered to gradually reduce ammonia levels while controlling the rebound effect 1.
Overall, the choice of initial treatment for hyperammonemia should be individualized based on the patient's clinical presentation, ammonia level, and underlying condition, with the goal of rapidly reducing ammonia levels and preventing neurological damage.
From the Research
Treatment Options for Hyperammonemia
The most recommended initial treatment for hyperammonemia is a topic of ongoing research and debate.
- Lactulose and rifaximin are commonly used to treat hyperammonemia, as they help reduce ammonia levels in the body 2, 3.
- These medications work by targeting the organs and metabolic processes involved in ammonia detoxification, and have been shown to be effective in reducing ammonia levels and alleviating symptoms of hepatic encephalopathy 2, 3.
- However, some studies suggest that lactulose may not always be the most effective treatment option, particularly in patients without chronic liver disease or significant hepatocellular injury 4.
- In some cases, intravascular resuscitation may be beneficial in treating dehydration-associated pseudo-hyperammonemia, and may be considered as an alternative to lactulose 5.
Factors Influencing Treatment
The decision to use lactulose or other treatments for hyperammonemia may depend on various factors, including:
- The severity of hyperammonemia and the presence of underlying liver disease 6.
- The patient's overall health status and the presence of other medical conditions 4.
- The potential benefits and risks of different treatment options, including the risk of adverse effects and interactions with other medications 2, 3.
Current Research and Recommendations
Current research suggests that lactulose and rifaximin remain the mainstay of treatment for hyperammonemia, but that other treatment options may be considered in certain cases 2, 3.
- Further research is needed to fully understand the role of ammonia in the pathophysiology of hepatic encephalopathy and to develop more effective treatment options 2, 3.
- The use of ammonia levels to guide treatment decisions is not always supported by the evidence, and other factors such as the patient's clinical presentation and overall health status may be more important in determining the best course of treatment 6.