Which of the following alcohol ingestions will produce a ketosis without acidosis on laboratory work-up?
d) Ethylene glycol
The patient (AB) is a 44-year-old Caucasian female with a past medical history significant for type 2 DM, HTN, long standing depression, and alcoholism who presents via EMS from home after her significant other found her intoxicated on the floor. Upon arrival to the ED at 19:30, the patient is placed in a room and the nurse tells the resident that another “drunk” has arrived.
The physician finds an intoxicated, middle-aged, unkempt female lying on her side. She is noted to be having a bout of emesis (non bloody, non bilious). AB is lethargic, but does respond to voice. She has a gag and is protecting her airway. Her speech is slurred, and she tells the resident, “I started drinking around 6PM; I just wanted to get drunk; Leave me alone.” She denies ingesting any other medications, drugs of abuse, or other substances. AB also denies suicidal/homicidal ideation.
Physical exam shows the following vital signs: Temp 36.2, HR 111, BP 94/56, RR 18 w 96% on RA. AB has reactive pupils bilaterally. Her breath has a faint sweet smelling odor. The patient is noted to have a grade II/VI systolic murmur; lung sounds clear. Her abdomen is benign. Other than being intoxicated, her neurological exam is grossly non-focal.
A FSBG reads “critically high”. Due to AB’s history of diabetes and her recent alcohol ingestion (which should have made her hypoglycemic), the resident is concerned about the possibility of a diabetic keto-acidosis presentation. Basic labs are sent off, including: BMP, serum ketones, ethanol level, urine analysis, and a urine drug screen. An IV and maintenance fluids are started.
AB’s labs are processed, and the resident is surprised to find the following labs:
gluc: 517, UA: gluc 4+, ketones 1+, otherwise normal, Ethanol: neg
FS Ketones: 0.2 UDS: neg
A quick calculation shows an anion gap of 11 and no ethanol on board. This argues against both of the initial suspicions: no acute ethanol intoxication and no DKA. The resident also notes the trace ketones in her urine and remembers the PE finding of the “sweet breath”. A serum osmolality and serum drug screen are sent off. Secondary labs:
Osmolality: 363 Serum Drug: neg for acetaminophen, neg for salicylates.
The resident calculated AB’s osmolar gap to be 54: elevated. Putting all of this lab data together, the physician arrives at a new diagnosis (no anion gap, elevated osmolar gap, trace ketones in urine, acetone odor to breath, hypotension, and quick onset of intoxication): ISOPROPYL ALCOHOL INGESTION. To cover all bases, the resident asks the nurse to also send off an ethylene glycol level and a methanol level (even though labs show a normal anion gap). The resident returns to the room, arouses AB and questions her about what brand of alcohol she drank. She finally admits to drinking half a bottle of rubbing alcohol (her significant other has cirrhosis and refuses to allow ethanol in the house). Arrangements are made for an in-patient bed and supportive care is continued.
The “toxic alcohols” generally refer to Methanol, Ethylene glycol, and Isopropanol. The amount of inebriation is directly related to the length of the parent carbon chain with isopropyl alcohol being the most inebriating. Isopropanol is usually found in rubbing alcohol, lacquer thinners, and other solvents. It is unique in that it is converted by alcohol dehydrogenase into acetone thus causing a “ketosis without acidosis”. This separates it from the other two toxic alcohols. Lab values will show an elevated osmolar gap and trace positive urinary ketones (due to the acetone metabolite). No acidosis will be noted in the lab work-up. Large ingestions of isopropyl alcohol may cause prolonged severe hypotension that requires direct alpha pressors. In refractory cases (rare), hemodialysis may even be required. The usual care is supportive, with aggressive fluid replacement and admission for observation, “sobering”, and counseling.
Often the lab will require multiple hours to run a methanol/ethylene glycol level. In theses cases it can be useful to use equation #1 (see figure 1) to calculate the osmol gap. A gap of 50 mOsm/L or greater is virtually diagnostic of a toxic alcohol ingestion. Once the gap is calculated, the estimated serum toxic alcohol level can be derived by using equation #3. The danger level of methanol and ethylene glycol is 25mg/dL. Levels above this range need treatment with ethanol therapy, fomepizole, or even nephrology consult for possible dialysis. It is critically important to understand that the elevation of the osmolar gap is due to the unmetabolized parent compound. In the case of methanol or ethylene glycol, a non-lactate, non-ketone anion gap metabolic acidosis develops as the serum osmolality falls.
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Pearls of the toxic alcohol work-up
1) Patients who have ingested significant amounts of methanol and are late in the presentation may complain of subjective blindness or “snow vision. The bedside funduscopic exam may show disc pallor.
2) Patients who have ingested ethylene glycol may report a “sweet-tasting alcohol”. Sometimes flourescein is included in ethylene glycol mixtures and a urine fluorescence test may be positive. However, glass and many plastics fluoresce, rendering this test largely useless in the diagnosis.
3) Isopropanol is the second most commonly ingested alcohol behind ethanol with pediatric patients and alcoholics being the main offenders. The most common source is rubbing alcohol which is 70% isopropyl alcohol. Data from 1998 shows that isopropanol accounted for approximately twenty thousand exposures (19,301) as reported to US poison centers. Of these ingestions 83 (0.4%) resulted in major toxicity and 3 (0.02%) resulted in death.
4) Toxicity leads to respiratory depression usually within 30 minutes of ingestion (which causes the majority of complications).
5) The patient will appear intoxicated but may not have the odor of ethanol; instead you may note the fruity odor of acetone. Complications are usually seen at blood levels greater than 400mg/dL, and hemodialysis should be considered at these toxic levels (or if hypotension is refractory to pressors).
6) The patient’s history with details regarding the suspected ingestion (from the patient, family members, EMS or bystanders) is the most important key in the work-up. Once suspicion is triggered, direct laboratory values can confirm and quantify isopropanol serum concentrations.