Severe lactic acidosis and acute hepatic and renal insufficiency due to fenaminosulf poisoning

To the Editor:

Fenaminosulf is a fungicide and micro-biocide that improves agriculture crop yields, that inhibits mitochondrial energy metabolism and adenosine triphosphate (ATP) production via specific interactions with electron transport proteins, as well as nonspecific disruption of the mitochondrial membrane's ability to employ an electrochemical proton gradient driving ATP synthesis.^1–3 Fenaminosulf is moderately toxic in animal studies⁴ but no detailed information on acute or chronic effects could be found,⁵ because the compound is not registered in the USA or Europe and is on the WHO obsolete list.⁶ We present an oral poisoning case that a 25-year-old female ingested approximately 10 g of fenaminosulf powder in a suicidal attempt. One day after her admission, she developed oliguria and excruciating abdominal pain. The patient was diaphoretic with elevated pulse (130 beats/minute), hypotension (98/62 mmHg), and shortness of breath with tachypnea (38 breaths/minute). The oxygenation index remained normal. Repeat laboratory analysis revealed a severe lactic acidosis, acute hepatic, and renal insufficiency. Her hematological and respiratory systems were also affected (Table 1). In order to treat the patient's severe lactic acidosis and acute hepatic/renal failure, she received hemoperfusion therapy combined with continuous venous-venous hemofiltration (CVVH) over 5 days, followed by five sessions of hemodialysis (HD) approximately every 3 days. Her secondary bacterial pneumonia was treated by extended courses of antibiotics. Reduced glutathione sodium and polyene phosphatidyl choline were administered to treat her hepatic injury. 800 ml of red blood cells suspension and 600 ml of fresh frozen plasma were transfused to correct her severe acute anemia and coagulation disorders. An anti-inflammatory drug (Ulinastain) and intravenous fluid support were also administered. Under this therapy the patient fully recovered and was discharged on Day 33 (Table 1). The development of the patient's severe lactic acidosis may be due to a similar mechanism to its biological action in plants. Mitochondria, injured by fenaminosulf or its metabolites, cannot continue ATP synthesis at a rate required to provide the cell adequate energy. Glycolysis is increased to provide additional ATP, and excess produced pyruvate is converted to lactate, and released into the circulation, where it accumulates over time. While increased glycolysis mitigates ATP deficiency from deficient oxidative phosphorylation, it cannot bind the protons resultant from ATP hydrolysis. Therefore, proton concentration increases, causing acidosis.⁷ The conversion reaction of overproduction of lactic acid requires entry of pyruvic acid into the mitochondria or the gluconeogenesis pathway, undertaken mainly by the liver and kidney. But because of the impaired mitochondria, such metabolism could not be successfully completed, since oxygen supply to the mitochondria is important, as are intact enzyme systems like pyruvate dehydrogenase in oxidation and pyruvate carboxylase in gluconeogenesis. This vicious cycle negatively affects many organs, particularly the liver and kidneys. Following absorption of fenaminosulf, there may be a possible toxic cascade-like reaction in the general circulation. A low threshold of suspicion must be maintained, to swiftly diagnose and treat severe lactic acidosis and acute hepatic and renal insufficiency, which may be delayed in onset after initial poisoning. Broad spectrum antibiotics should be initiated if secondary infectious, particularly in the pulmonary system, are identified. Intravenous fluid resuscitation and aggressive HD may be life-saving.

Table 1. Physiological indices post fenaminosulf ingestion.

	Parameter	Day 2	Day 33
Arterial blood gas analysis indices	pH	7.033	7.38
	Base excess (BE), mmol/L	− 27	1
	Bicarbonate ion concentration (HCO3^−), mmol/L	9.3	25
	Potassium concentration (K), mmol/L	6.9	3.7
	Carbon dioxide combining power (CO2), mmol/L	4.1	23.2
	Anion gap (AG), mmol/L	42.5	12.1
	Lactate concentration (Lac), mmol/L	17.3	1.8
Hepatic function indices	Total bilirubin (TBIL), umol/L	91.3	17.4
	Conjugated bilirubin (DBIL), umol/L	73.9	13.6
	Unconjugated bilirubin (IBIL), umol/L	17.4	3.8
	Alanine aminotransferase (ALT), IU/L	2183	17
	Aspartate aminotransferase (AST), IU/L	2722	27
	Albumin (Alb), g/L	24.1	31.3
Renal biological values	Urea nitrogen (BUN), mmol/L	15.97	6.12
	Serum creatinine (CREA), umol/L	740	136
Hematologic indices	Red blood cell count (RBC), × 10^12/L	2.06	2.72
	Hemoglobin (Hgb), g/L	63	85
	Platelet (PLT), *10^9/L	79	112
	Fibrinogen (FIB), g/L	0.89	3.24

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.