Diethylene glycol is a clear liquid often used as an industrial diluent. It is a potent nephrologic and neurologic toxicant in humans.1 Ingestion of diethylene glycol may lead to acute kidney injury because of acute tubular necrosis and may also result in neurologic symptoms such as acute flaccid paralysis, cranial nerve palsies, and encephalopathy.1 Diethylene glycol poisoning has occasionally resulted from the intentional ingestion of diethylene glycol–containing industrial products.1 However, most cases of diethylene glycol poisoning are due to pharmaceutical products formulated with diethylene glycol as a diluent instead of a safe agent such as pharmaceutical-grade glycerine or propylene glycol. Distribution and human consumption then typically results in mass poisoning incidents.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 The more recent outbreaks of diethylene glycol poisoning up until this incident have occurred more commonly in children and are associated with variable case-fatality rates, but may be as high as 98%4, 7, 8, 10, 17, 18 (Table 1).Editor's Capsule Summary
What is already known on this topic
The substitution of diethylene glycol for glycerin has resulted in mass pediatric poisonings characterized by fulminant acute kidney injury and death. However, little is known about diethylene glycol poisoning of adults.
What question this study addressed
The renal and neurologic findings in mass poisoning of 46 adults resulting from contaminated cough syrup.
What this study adds to our knowledge
Severe neurologic effects developed in 87% of victims, including limb or facial motor weakness, and 59% died despite use of intensive care.
How this is relevant to clinical practice
A high proportion of adult patients with diethylene glycol poisoning developed progressive neurologic effects, in addition to acute kidney injury. Facial or limb weakness with unexplained acute kidney injury should prompt clinicians to consider diethylene glycol poisoning.
In September 2006, an unusually large number of patients presenting with limb weakness and acute kidney injury were noted by physicians at the Social Security Metropolitan Hospital in Panama City, Panama. A subsequent international public health investigation identified the illness as resulting from the ingestion of a domestically produced sugarless cough syrup referred to locally as “expectorante sin azucar” (“sugarless cough syrup”).14 Extensive testing of biological and environmental samples associated with cases for multiple analytes, including metals, pesticides, glycols, and others, revealed diethylene glycol as the only possible cause (unpublished data). A nationwide assessment by the Panama Ministry of Health ultimately identified 119 cases of diethylene glycol poisoning that occurred between June 1 and October 22, 2006. Estimates of the number of citizens exposed to diethylene glycol according to product distribution records number in the tens of thousands. The true number of persons adversely affected by diethylene glycol exposure to some extent, but who remained undiagnosed, is probably higher.14 This incident represents one of the largest outbreaks of diethylene glycol poisoning to date, to our knowledge: the first occurred in the United States during 1936, possibly affected 353 persons and killed 105 of them.2, 3
The majority of the patients in the Panama outbreak (n=68; 57%) were hospitalized at Social Security Metropolitan Hospital. Previous published reports of similar mass poisoning incidents have described very limited clinical, laboratory, and neurologic data. The lack of data is probably because most poisonings involved children who died rapidly (within days) after exposure (likely because of a higher dose per unit body weight) and because they tend to occur in developing countries with poor access to tertiary level care capabilities and more pressing public health problems precluding detailed study of survivors.5, 6, 7, 8, 9, 10, 11, 12, 13, 17, 18 In contrast, the majority of patients in this incident were adults (who likely received a lower dose per unit body weight compared with that of past outbreaks) and survived for several days after exposure. This enabled close observation and documentation of the clinical course of poisoning. Although diethylene glycol–associated acute kidney injury and mortality are well characterized among these outbreaks and among individual case reports of illness, signs and symptoms of diethylene glycol–associated neurotoxicity are not. Most of the detailed data available on neurotoxicity resulting from diethylene glycol ingestion to date come from 3 case reports of 1 patient each and a small case series (n=3).19, 20, 21, 22, 23
We characterized the demographic characteristics, clinical findings, laboratory results, diagnostic study findings and histopathology of 46 cases of acute diethylene glycol poisoning. To our knowledge, this article is the largest and most extensive collection of clinical, laboratory, and diagnostic information on human mass diethylene glycol poisoning. It is also the single largest and most detailed source of data on diethylene glycol–associated neurotoxicity to date.