P0446 - A Zebra Revealed: The “Other” Complications of Anesthesia

A 6-month-old male with Poland syndrome and normal development presented with lethargy, hypotonia, and shock. He was admitted to the ICU with presumptive Mycoplasma/Coronavirus (non-SARS-CoV2) PCR-positive sepsis. Due to persistent hypotonia despite fluid resuscitation, he was given botulism immune globulin for possible infantile botulism. Though hemodynamic and laboratory values improved, his persistent hypotonia and newly developed areflexia prompted concern for alternative neurologic etiologies necessitating a brain and spine MRI with propofol sedation. Twenty-four hours after sedation, he had acute decompensation requiring intubation, pressor support, and continuous renal replacement therapy due to severe lactic acidosis.

On exam, he was irritable. Vitals showed desaturations and bradycardia. He exhibited respiratory distress with poor secretion clearance and increased work of breathing. Extremities were cool, capillary refill was delayed, and distal pulses were weak. Neurologic exam demonstrated diffuse hypotonia and severe head lag. He had weakness of palate elevation and a hoarse, weak cry. Strength was diminished throughout and worse in the lower extremities compared to the upper extremities. Reflexes were absent in the lower extremities and diminished in the upper extremities.

Initial laboratory analysis revealed ketotic hypoglycemia to 38 mg/dL. Venous blood gas showed anion gap metabolic acidosis with incomplete compensatory respiratory alkalosis (Table 1). Low level lactic acidosis (4.3mmol/L) persisted prior to sedation and abruptly worsened 24h after sedation with lactic acid peaking at 15.5 mmol/L. Liver enzymes (near normal on admission) significantly increased (ALT 1059 U/L and AST 2798 U/L). Mycoplasma was confirmed with positive IgM and negative IgG. Botulism testing returned negative. Bedside echocardiogram showed poor function (normal on admission). Magnetic resonance imaging showed a symmetric myopathy (Figure 1).

The differential for his persistent hypotonia was concerning for an infectious or post-infectious encephalitis or polyneuropathy, botulism, Guillain-Barre syndrome, motor neuron disease, or congenital myopathy. Given persistent metabolic acidosis, there was concern for a Mycoplasma/Coronavirus (non-SARS-CoV2) infection triggering a metabolic crisis leading to his initial presentation. The abrupt shock and multiorgan failure shortly after sedation suggested that propofol had exacerbated the crisis due to a mitochondrial metabolic disorder. Rapid whole genome sequencing revealed a rare homozygous NFS1 mutation affecting the iron-sulfur complex and causing mitochondrial dysfunction, specifically in the respiratory chain I/II pathways. A mitochondrial cocktail including acetylcysteine was started, and he slowly improved. At time of discharge, his cardiac and renal function had normalized, and his liver enzymes were nearly normal. When he is unwell in the future, the priorities of his medical management will be to decrease metabolic demands and limit anesthetic exposure.

Complications can occur after anesthetic exposure. Propofol inhibits multiple respiratory complex enzymes, uncouples oxidative phosphorylation, and reduces utilization of fatty acids. Mitochondrial defects should be considered in patients who decompensate after exposure to propofol or other anesthetics.