Treatment options include observation, gastrointestinal decontamination, supportive care, administration of an ADH inhibitor therapy, and hemodialysis. There is no evidence of clinical benefit or even reduced bioavailability of DEG following gastric or nasogastric lavage or the administration of oral activated charcoal.26 Nevertheless, given the limited data regarding the role of gastrointestinal decontamination techniques in DEG poisoning, the profound dose-related clinical effects, and the liquid state of the xenobiotic, nasogastric lavage for an individual who presents soon after ingestion for a significant amount may help remove unabsorbed DEG. Since absorption begins immediately after ingestion, the efficacy of lavage after one hour is probably minimal.
Animal evidence suggests that the osmotic diuretic effect of DEG can cause large urinary volume losses in the immediate postexposure period which may not be effectively corrected due to concurrent inebriation. Adequate volume repletion and resuscitation should be performed as soon as possible. The patient should be closely monitored for decreases in urine output, fluid input and output recorded, their function tests closely followed, and appropriate fluid adjustments made for any signs of AKI. There is currently no evidence for forced diuresis; however, all patients should be aggressively hydrated (after appropriate resuscitation if needed) to ensure maintenance of euvolemia and a steady urine output. This is for several reasons, including (1) DEG is primarily eliminated unchanged in the urine via the kidneys, (2) inadequate resuscitation and/or suboptimal hydration beyond the initial fluid resuscitation period may contribute to prerenal azotemia thereby decreasing elimination of unchanged DEG, (3) any impairment in kidney function will result in decreased elimination of unchanged DEG with a corresponding increase in available DEG for metabolism to toxic metabolites such as DGA, and (4) animal studies suggest that when doses associated with adverse health effects (10 g/kg) are given in addition to fomepizole, almost the entire dose is eliminated unchanged in the urine.3,30 Careful attention to acid-base status is advised since limited in vitro work with DGA and human proximal tubule cells suggest that acidemia may enhance DGA’s toxicity.30,31 Intravenous bicarbonate therapy may be of benefit in treating DEG-associated metabolic acidosis for this reason, but this is unstudied.
Available evidence supports the use of an ADH inhibitor such as fomepizole in suspected or known DEG poisoning to prevent nephrotoxicity, although most of this evidence is from animal studies. This same evidence suggests that the parent compound is not nephrotoxic.4,30,57 However, there is no evidence demonstrating that the parent compound is not neurotoxic (the mechanism of DEG associated neurotoxicity is still completely unstudied). Because neurotoxicity seems to only appear following DEG metabolite-associated AKI, the likelihood of the parent compound being neurotoxic seems low. Fomepizole monotherapy for DEG poisoning may be entirely appropriate (similar to other toxic alcohols); however, definitive evidence is lacking. Furthermore, data to guide dosing and duration of administration are also lacking. Considering the aforementioned factors and the current lack of human data confirming safety and efficacy of fomepizole in DEG poisoning, patients presenting soon after (within a few hours) a highly suspected or known moderate to large ingestion of DEG should be started on fomepizole therapy and then urgently hemodialyzed if available. If hemodialysis is not available the patient should be transferred to a facility with that capability. Although the minimal toxic dose is unknown, cumulative exposures at or above 250 mg/kg (the lower limit of the range reported in the Haiti mass poisoning) should be considered potentially life threatening. A single report documented higher prehemodialysis and lower posthemodialysis concentrations of DEG suggesting that it is cleared by hemodialysis, although the gradient was relatively small (0–1.6 mg/dL).7 Nevertheless, the volume of distribution and molecular weight of DEG suggest that hemodialysis should be effective.20,46 The endpoint of fomepizole therapy or need for additional rounds of dialysis is unclear, but the relatively new commercial availability of techniques for the determination of whole blood, plasma, serum and urine DEG concentrations with careful attention to acid-base status should be helpful in guiding therapy. Considering the lack of fomepizole data in DEG poisoning, dosing should be comparable with the treatment regimens for the other toxic alcohols (Antidotes in Depth: A30).
Exposures to amounts less than those known to be associated with poisoning present management dilemmas. The following sections consist of suggested guidelines which may need to be modified depending on the individual situation. In all exposures, a toxicologist should be consulted as the circumstances surrounding the exposure are invariably different and may affect management.
Outbreak-derived toxic doses of DEG are not reliable measures for excluding poisoning. Patients with a reliable history of a minimal ingestion, such as an unintentional sip of a low concentration DEG containing product, are unlikely to be at risk for toxicity. Those adult patients with slightly larger DEG ingestions with relatively low concentrations liquids (< 10%) such as exposures consisting of more than a sip but less than a “mouthful” can be considered for careful observation alone, as long as it is coupled with serial chemistries and blood gas measurements to rapidly identify onset of renal function and acid-base abnormalities. Although the true minimum toxic dose of DEG is unknown, an example of the aforementioned situation might involve an unintentional ingestion of 30 mL (mouthful) of a 5% DEG product by volume in an adult. This is approximately 1.5 mL of DEG which is equivalent to about 1.7 g, which in an 80-kg adult is about 21 mg/kg. The lower end of the estimated toxic dose range in Haiti was 250 mg/kg, which is more than 10 times higher (1090% increase). Therefore careful observation might be reasonable in this situation if you believed you had correct values for the dose and product concentration and there were no other potential risk factors for DEG-associated illness (eg, preexisting renal disease). Such an exposure in a 3 year-old child weighing 16 kg would yield a dose of 110 mg/kg, an exposure of greater concern that might warrant more aggressive treatment. Unfortunately, ascertainment of the true volume ingested and product concentration may be difficult, which contributes to the problem of estimating risk based on patient history.
Patients with signs or symptoms of alcohol intoxication, but who did not consume ethanol should be suspected of having a potentially life threatening DEG ingestion and treated as discussed in the previous section. Asymptomatic patients with ingestions beyond the “unintentional sip or taste” should probably be observed for at least 24 hours regardless of therapy offered. Serial laboratory determinations should be obtained and evaluated for at least 24 hours following exposure based on what is known of DEG toxicokinetics.
Fomepizole monotherapy (without hemodialysis) can be considered at the discretion of the attending physician and consulting toxicologist or poison center, as emerging evidence suggests that fomepizole can prevent nephrotoxicity. However, if the decision to use fomepizole monotherapy is made, the physician should remember that, albeit unlikely, the safety and efficacy of fomepizole monotherapy in DEG poisoning is not yet established, thereby necessitating that the risks be explained to the patient.
Unless laboratory testing documents a minimal or nonexposure, the patient’s clinical, acid-base, and kidney function status should probably be followed for at least 24 hours for evidence of DEG poisoning. For patients receiving fomepizole, this 24 hour period should begin 12 hours following the last dose of fomepizole. If signs and symptoms of nephrotoxicity begin to appear, then fomepizole should be given and the patient hemodialyzed.
For those patients presenting to health care facilities with a metabolic acidosis, oliguria or anuria within 24 to 36 hours of an DEG ingestion, fomepizole should be given and emergent hemodialysis should be performed, regardless of the patient’s acid-base and electrolyte status. This suggestion is based in part on animal studies showing that serum DGA concentrations peak at 24 hours following ingestion, DGA sequesters in kidney tissue, it is nephrotoxic,3,30 and half-lives increase with larger doses.3 Early presentation to health care facilities (< 10 hours from ingestion) and aggressive treatment (gastrointestinal decontamination, fomepizole, and hemodialysis) appeared to be associated with better outcomes in the five reports in which fomepizole or ethanol was administered for DEG exposure.1,5,7,19,43 In one of these cases, a 15 year-old girl who was witnessed to ingest approximately 22.4 g of DEG (patient’s weight was not reported) was managed with orogastric lavage and early (< 3 hours) fomepizole therapy alone; the patient had a good outcome with no renal or neurological dysfunction (other than inebriation).5 For those patients presenting later than 36 to 48 hours after a DEG ingestion with the aforementioned signs and symptoms, fomepizole and hemodialysis should be considered, but may be too late to be beneficial with regard to removal of DEG and toxic metabolites. However, it may be of value with regard to electrolyte imbalances and or AKI.
Although there are no published reports examining the efficacy of ethanol to block DEG metabolism, it is expected to act similarly to fompeizole. Hence, it may be an alternative therapy if fomepizole and hemodialysis are unavailable and a rapid transfer to another hospital is not possible.