Overview

Propionic acidaemia is an autosomal recessive disorder of propionate catabolism caused by a defect in the propionyl-CoA carboxylase (PCC) enzyme.

The clinical picture may be either early, with metabolic acidosis and hyperammonaemia shortly after birth, or with a more heterogenous picture later in childhood.

Complications include severe neurological handicap, cardiomyopathy and life-threatening metabolic decompensation. The neurological impact is related to the frequency and severity of episodes of hyperammonaemia.

Among the few therapeutic options for this disease is liver transplantation, which reduces the frequency and severity of metabolic crises by providing the recipient with a source of functioning PCC enzyme. [Sophoclis et al, 2020]

The incidence of propionic acidaemia is unknown, but estimated at between 1:50,000 and 1:500,000 in Western populations; higher in the Greenland Inuit and Saudi Arabian populations.

[Baumgartner et al, 2014] [Ravn et al, 2000]

Pathophysiology

Propionic acid is a carboxylic acid formed by the breakdown of various fatty acids and several amino acids. With a deficiency in PCC, metabolites accumulate leading to metabolic acidosis, hyperammonaemia and resultant encephalopathy and neurological deterioration.

Therapy is aimed at avoiding acute metabolic events, by:

• Reducing exposure to substrates that lead to propionic acid accumulation
• Therapy with L-carnitine, which can increase the excretion of propionyl groups via an alternative pathway

Impacts on anaesthesia

Goals for the anaesthesia care of these patients is directed at reducing the substrate available for the defective PCC enzyme, via protein catabolism or administered drugs.

Neuromuscular blocking agents undergoing ester hydrolysis

Theoretical Suxamethonium, cisatracurium, atracurium and mivacurium all give rise to odd-chain organic metabolites that are a substrate for the PCC enzyme, which theoretically may increase accumulation of propionic acid. [Alex et al, 2021]

However, mivacurium and atracurium have been used uneventfully in patients with similar organic acidaemias. [Fuentes-Garcia, 2009]

Remifentanil use has been reported without issue. [Rafiq et al, 2015]

Propofol

Case reports A subset of the polyunsaturated lipids in propofol may be metabolised to propionic acid, and some authors recommend against its use. However, many case reports have demonstrated that propofol boluses at induction appear to be safe. A series of 28 patients who received propofol for anaesthesia maintenance (for procedures 60 to 325 minutes long) had two adverse events, neither of which were attributed to propofol. [Ktena et al, 2015]

Drugs derived from propionic acid

Theoretical Multiple NSAIDS are derived from priopionic acid and should probably be avoided, including:

• Ibuprofen
• Naproxen
• Fenoprofen
• Ketoprofen
• Flurbiprofen
• Oxaprosin

Prolonged QT

Expert opinion Accumulation of propionic acidaemia metabolites appears to impact repolarising potassium currents, with a resulting propensity to prolonged QT. [Bodi et al, 2016]

Swallowed blood

Theoretical Blood swallowed during surgery involving the oropharyngeal cavity represents a significant protein load. It may be prudent to suction gastric contents or use a pharyngeal pack in these cases.

Perioperative fasting

Expert opinion Minimising fasting times and providing oral or intravenous glucose-containing solutions helps to reduce the risk of protein catabolism with resultant propionic acid accumulation. [Alex et al, 2015]

Hartmann's solution / Ringer's lactate

Case series A series of 11 patients with propionic acidaemia who underwent 19 anaesthesia episodes (17 where Hartmann's solution was administered) demonstrated no clear association with adverse events. Only one of these patients had a mild lactic acidosis after receiving Hartmann's solution - in the context of massive transfusion during spinal surgery.

Given that metabolism of lactate to glucose is not affected in propionic acidaemia, it is unlikely that lactate-containing fluid has a clinically significant adverse effect on these patients.

[Ruzkova et al, 2015]