Presented at the Neonatal Society 2001 Summer Meeting.

Whitelaw A, Bridges S, Leaf A, Evans D

Neonatal Intensive Care Unit, Southmead Hospital, Bristol BS10 5NB, UK

In infants with inherited urea cycle disorders, hyperammonaemic coma lasting more than 5 days is always associated with severe neurodevelopmental delay whereas coma lasting less than 3 days may have a good outcome (1). However, catabolism may predominate and high rates of ammonia production may mean that treatments such as haemofiltration, dialysis and metabolite therapy do not lower the plasma ammonia rapidly enough to protect the brain. We hypothesised that mild systemic hypothermia might be protective in this situation by reducing enzymatic production of ammonia and reducing extracellular glutamate (2).

An infant presented at 3 days with hyperammonaemic coma and seizures due to carbamyl phosphate synthetase deficiency. Haemofiltration, alternative pathway metabolites and glucose/insulin failed to lower the plasma ammonia below 2,000 μmol/l. The infant was then cooled to a rectal temperature of 34ºC for 48 hours and again haemofiltered for 12 hours.
Plasma ammonia fell to around 100 μmol/l and remained at this level after haemofiltration. He awoke, breathed spontaneously and resumed bottle feeding.

Hypothermia may be therapeutic in this and possibly other metabolic comas by lowering the enzymatic rate of production of the toxin while non-enzymatic methods remove the toxin.

References
1. Msall M, Batshaw ML, Suss R. Neurological outcome in children born with inborn errors of urea cycle disorders. N Eng J Med 1984;310:1500
2. Thoresen M, Satas S, Puka-Sundvall M, Whitelaw A, Hallstrom A, Loberg EM, Ungerstedt U, Steen PA, Hagberg H. Post-hypoxic hypothermia reduces cerebrocortical release of NO and excitotoxins. Neuroreport 1997 Oct 20; 8: 3359-62