Toxicology/original research
Clinical, Laboratory, Diagnostic, and Histopathologic Features of Diethylene Glycol Poisoning—Panama, 2006

Presented at the 2007 North American Congress of Clinical Toxicology, October 2007, New Orleans, LA.
https://doi.org/10.1016/j.annemergmed.2013.12.011Get rights and content

Study objective

Diethylene glycol is a toxic industrial solvent responsible for more than 13 mass poisonings since 1937. Little is known about the clinical spectrum, progression, and neurotoxic potential of diethylene glycol–associated disease because of its high mortality and the absence of detailed information in published mass poisoning reports. This incident includes the largest proportion of cases with neurotoxic signs and symptoms. We characterize the features of a diethylene glycol mass poisoning resulting from a contaminated cough syrup distributed in Panama during 2006.

Methods

This was a retrospective chart review and descriptive analysis in a tertiary level, urban health care facility. A case was a person admitted to the Social Security Metropolitan Hospital in Panama City between June 1 and October 22, 2006, with unexplained acute kidney injury and a serum creatinine level of greater than or equal to 2 mg/dL, or unexplained chronic renal failure exacerbation (>2-fold increase in baseline serum creatinine level) and history of implicated cough syrup exposure. Main outcomes and measures were demographic, clinical, laboratory, diagnostic, histopathologic, and mortality data with descriptive statistics.

Results

Forty-six patients met inclusion criteria. Twenty-four (52%) were female patients; median age was 67 years (range 25 to 91 years). Patients were admitted with acute kidney injury or a chronic renal failure exacerbation (median serum creatinine level 10.0 mg/dL) a median of 5 days after symptom onset. Forty patients (87%; 95% confidence interval [CI] 74% to 95%) had neurologic signs, including limb (n=31; 77%; 95% CI 62% to 89%) or facial motor weakness (n=27; 68%; 95% CI 51% to 81%). Electrodiagnostics in 21 patients with objective weakness demonstrated a severe sensorimotor peripheral neuropathy (n=19; 90%; 95% CI 70% to 99%). In 14 patients without initial neurologic findings, elevated cerebrospinal fluid protein concentrations without pleocytosis were observed: almost all developed overt neurologic illness (n=13; 93%; 95% CI 66% to 100%). Despite use of intensive care and hemodialysis therapies, 27 (59%) died a median of 19 days (range 2 to 50 days) after presentation.

Conclusion

A high proportion of patients with diethylene glycol poisoning developed progressive neurologic signs and symptoms in addition to acute kidney injury. Facial or limb weakness with unexplained acute kidney injury should prompt clinicians to consider diethylene glycol poisoning. Elevated cerebrospinal fluid protein concentrations without pleocytosis among diethylene glycol–exposed persons with acute kidney injury may be a predictor for progressive neurologic illness.

Introduction

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.

Section snippets

Materials and Methods

The study design was a case series developed from a retrospective review of medical records. Three investigators conducted all the data abstractions (G.M.R., Ricardo Sandoval, Josefina Fletcher), which were reviewed again by a principal investigator (G.M.R.) and followed the general principles outlined by Gilbert et al24 for chart abstraction. The data abstractors were all physicians with experience conducting chart abstractions. Outcome variables of interest were developed a priori and a

Results

Sixty-eight patients were hospitalized at Social Security Metropolitan Hospital with unexplained acute kidney injury during the study period; 46 (81%) of these patients fulfilled our case definition and were included in the analysis. Of these, 41 (89%) met the case definition because of new-onset acute kidney injury (n=41; 89%) and 5 (11%) met the case definition because of an exacerbation of their chronic renal failure. Twenty-four (52%) of these 46 cases were of female patients; median age

Limitations

The most serious limitation of our study is that laboratory confirmation of exposure could not be obtained at the investigation because there was no readily available assay for confirming diethylene glycol exposure. However, the CDC developed a urinary diethylene glycol assay that was applied to a subsample of cases, and results indicated significantly higher concentrations of urinary diethylene glycol in case patients compared with controls.14 When this fact is combined with the following

Discussion

There have been at least 13 other instances of medication-associated diethylene glycol mass poisoning since the first recognized event occurred in the United States in 1937 (diethylene glycol–contaminated elixir of sulfanilamide).1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 Most of these contaminations have occurred in developing countries, in which access to tertiary health care facilities did not exist or was limited. This likely contributed to the high case-fatality rates

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    Supervising editor: Richard C. Dart, MD, PhD

    Author contributions: NRS and GMR conceived of the study and performed data collection. All authors participated in the analysis and drafting of the article. JJS takes responsibility for the paper as a whole.

    Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist and provided the following details: Funded in part by the Division of Global Disease Detection and Emergency Response, Centers for Disease Control and Prevention.

    The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

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