Guidelines for acute management of hyperammonemia in the Middle East region

Abstract

BackgroundHyperammonemia is a life-threatening event that can occur at any age. If treated, the early symptoms in all age groups could be reversible. If untreated, hyperammonemia could be toxic and cause irreversible brain damage to the developing brain.ObjectiveThere are major challenges that worsen the outcome of hyperammonemic individuals in the Middle East. These include: lack of awareness among emergency department physicians about proper management of hyperammonemia, strained communication between physicians at primary, secondary, and tertiary hospitals, and shortage of the medications used in the acute management of hyperammonemia. Therefore, the urge to develop regional guidelines is extremely obvious.MethodWe searched PubMed and Embase databases to include published materials from 2011 to 2014 that were not covered by the European guidelines, which was published in 2012. We followed the process of a Delphi conference and involved one preliminary meeting and two follow-up meetings with email exchanges between the Middle East Hyperammonemia and Urea Cycle Disorders Scientific Group regarding each draft of the manuscript.Results and discussionWe have developed consensus guidelines based on the highest available level of evidence. The aim of these guidelines is to homogenize and harmonize the treatment protocols used for patients with acute hyperammonemia, and to provide a resource to not only metabolic physicians, but also physicians who may come in contact with individuals with acute hyperammonemia.ConclusionThese suggested guidelines aim to ease the challenges faced by physicians dealing with acute hyperammonemia in the region. In addition, guidelines have demonstrated useful collaboration between experts in the region, and provides information that will hopefully improve the outcomes of patients with acute hyperammonemia.

Consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy

“…Once hyperammonaemia is identified, protein intake must be temporarily stopped and plasma ammonia levels monitored every 3 h (ref. 10 ). In a patient with an ammonia level at the upper limit of normal for their age — that is, 110 μmol/l (154 μg/dl) at age 1–7 days, <90 μmol/l (126 μg/dl) at age 8–14 days and 16–53 µmol/l (22–74 μg/dl) at age 15 days to adult — stopping protein intake and initiating intravenous glucose and lipids to prevent catabolism is generally adequate.…”

“…Ammonia is amenable to diffusive dialysis as it does not notably bind to albumin or other proteins and is a small molecule with a molecular weight of 17 Da 2 . Published indications for dialysis in neonates and children include serum ammonia level >500 μmol/l (852 μg/dl) or a lower level if there is an inadequate clinical response after 4 h of medical management 10 , 32 . If serum levels of ammonia are 100–300 μmol/l (170–511 μg/dl) and the patient shows clinical signs of severe encephalopathy and/or seizure, with consistent EEG findings, treatment with ammonia-scavenging agents (as recommended in Boxes 1 and 2 ) should be initiated.…”

“…Hyperammonaemia is defined as >100 µmol/l (170 µg/dl) in neonates or 50 µmol/l (85 µg/dl) in term infants, children and adolescents 10 . Individual laboratory reference intervals vary and some age dependency of ammonia levels is evident (that is, levels are higher in premature neonates).…”

Evaluation of long-term effectiveness of the use of carglumic acid in patients with propionic acidemia (PA) or methylmalonic acidemia (MMA): study protocol for a randomized controlled trial

“…Guidelines on acute management of hyperammonemia in the middle east region recommend the use of nitrogen scavengers, carnitine, in cases where the plasma ammonia levels are > 100 μmol/L (> 150 μmol/L in neonates), and continuous renal replacement therapy for ammonia levels > 500 μmol/L. [16] Similarly, guidelines on the diagnosis and management of PA and MMA suggest protein-restricted diet, L-carnitine, and metronidazole in the long-term management of these patients [9].…”

Perioperative management of children with urea cycle disorders

“…We placed the peripheral venous access the day before to avoid interrupting the night rest with an aggressive measure. The infusion rate of dextrose 10% with half saline was adjusted depending on the patient's age to determine the total glucose requirements 2,4‐7 :1‐12 months, 8‐10 mg/kg/min of dextrose; 1‐3 years, 7‐8 mg/kg/min; 4‐6 years, 6‐7 mg/kg/min; 7‐12 years, 5‐6 mg/kg/min; and adolescents, 4‐5 mg/kg/min. Prior to the procedure, the patients received their usual medication 5 .…”