Case of the Week COW#16

CC: BIB BLS for “Psych Evaluation”

HPI: 46-year-old female w/ PMH of asthma, SLE, RA and seizure disorder presents to the emergency department by BLS for evaluation. Patient states, “I don’t like people accusing me of doing things I didn’t do, I only took 2 Percocet and that’s it!” Patient states that she has been feeling depressed and “everything I do is never good enough for my kids, I buy them car, and I don’t even have car myself.” Patient appears to have multiple scratches over her face and left wrist, but is not willing to elaborate how she sustained them or provide any additional history. Denies any suicidal ideations, homicidal ideations, or hallucinations. There is no known psychiatric history.

Per family and EMS, patient was in her bedroom with the door shut, “not acting right, she was asking for us to pass her the key under the door to get out of the room but there is no lock on the door. She did this once before but it went away, today is more severe.” Pt was found in her bedroom by EMS with 2 empty beer cans and bottles of Percocet nearby. She had a recent URI for which she was taking Zzz-quil.

Medications: oxycotin 60mg q12h prn, Percocet 10/325mg q4-6h prn, toradol 10mg TID, ambien CR 12.5mg qHS, ProAir HFA 2 puffs q6h, Zzz-quil

 Physical Exam:

VS: 148/101, HR 111, RR 18, T 99.1, SpO2 95% on RA
General: Awake, alert, coherent, intermittently tearful
HEENT: superficial abrasions over face, otherwise NCAT; moist mucous membranes
Eyes: 3mm PERRL
Cardiac: tachycardic, regular rhythm, no M/R/G
Lungs: CTA b/l
Abd: soft, NT, ND, normal active bowel sounds
Neuro: AAOx3, lucid, following commands, moving all 4 extremities, no gross deficits, steady gait w/o difficulty
Skin: multiple superficial abrasions over face and L wrist, normal moisture
Extremities: 2+ distal pulses, warm, normal color
Psych: Anxious appearing, depressed mood, emotionally labile, intermittently tearful; denies SI/HI

Pertinent Labs (if any)
CBC: 11.7>16.5/50.1<324
CMP (@15:09 hours): Na 135, K 4.6, Cl 106, CO2 5, Glucose 132, BUN 9, Cr 0.98, GFR >60
Alk phosphate 77, AST 59, ALT 66
UA: Moderate blood, 0-3 RBCs, occasional calcium oxalate crystals, otherwise WNL
Alcohol: <10 mg/dl
UDS: (+) cocaine
Acetaminophen: <10.0 ug/ml
Salicylate: <2.5 mg/dl
Repeat CMP (@ 17:30 hours): Na 138, K 5.4, Cl 109, CO2 <2, Glucose 143, BUN 9, Cr 1.10 GFR:53, Alk phos 77, AST 69, ALT 74
Serum Osmolality: 334 mOsm/kg (N: 283-299)
Calculated osmolar gap: 53.0 mOsm/kg
ABG: pH 7.00 / pCO2 13 / pO2 151 / HCO3 – 3.2
ABG Lactate: 20.0 mmol/L
Serum lactic acid: 1.2 mmol/L
Acetone: Negative

ECG in the ED

Working Diagnosis: Anion gap metabolic acidosis, most likely due to ethylene glycol poisoning

ED/Hospital course:  In the ED patient became increasingly altered. Upon arrival patient was coherent, AAOx3, tearful. Upon reevaluation she was found in room shaking back and forth talking to herself and banging her hands on the bed rails, more confused, inappropriate in her thoughts and actions. A short time later she was found on the floor next to stretcher and was AAOx1, agitated, combative, not following commands, fighting with staff, incontinent of urine. Lab results returned at this time and the patient was subsequently intubated, received 1 amp sodium bicarbonate prior to intubation and admitted to MICU. Repeat labs in MICU showed persistent anion gap metabolic acidosis with Bicarbonate of 5 and anion gap of 26. She was placed on bicarbonate drip and received emergent HD. After HD, the acidosis improved with a bicarbonate value of 19 afterwards. Additionally placed on fomepizole. Received 2 rounds of HD. Subsequently extubated and transferred to floor. Upon extubation she continued to deny any SI or toxic ingestion. Methanol and ethylene glycol levels (-), however, they were drawn after HD was performed.

 Pearls: Brief differential diagnosis of anion gap metabolic acidosis:

  • Methanol, metformin
  • Uremia
  • Diabetic or alcoholic ketoacidosis
  • Paraldehyde
  • Isoniazid, Iron, Inhalants (carbon monoxide, cyanide, hydrogen sulfide)
  • Lactic acid
  • Ethylene glycol (ethanol may produce a small gap)
  • Salicylates, solvents

Osmolar gap:

  • Calculated osmolar gap ≥10 is consistent with poisoning by alcohols (ethanol, methanol, ethylene glycol, isopropanol, propylene glycol), glycerol or mannitol
  •  Absence of osmolar gap does not exclude toxic alcohol poisoning.
  • Normal osmolar gap: ±10
  • Normal serum osmolality: 280-295 mOsm
  • Osmolar gap formula: (2 x Na) + BUN/2.8 + Glucose/18 + Ethanol/4.6
  • Labs for this calculation (i.e. serum osmolality, ethanol, and SMA-7) must be drawn at the same time for accuracy

Toxic Alcohol Poisonings:

  1. Methanol
  • Found in windshield washing fluids, solvents, paint thinners and canned fuels
  • Converted by alcohol dehydrogenase to formaldehyde then to formic acid
  • Accumulation of formic acid correlates with the decrease in bicarbonate, the increase in anion gap, and the severity of the metabolic acidosis
  • Formic acid affects optic nerve function, causing optic papillitis and retinal edemaà “blind drunk”
  • Visual symptoms include photophobia, “snowstorm” vision, and blindness
    • Management:
      • Supportive measures including airway management
      • Severe acidosis is treated with bicarbonate to reduce diffusion of formate into the CNS and protect the optic nerve
      • Alcohol dehydrogenase inhibitor (ethanol or fomepizole) to block further metabolism of methanol
      • Fomepizole Fomepizole (4-methylpyrazole) is preferred iv.
      • Hemodialysis to remove methanol and formic acid indicated if methanol level >50 mg/dL, metabolic acidosis (arterial pH ≤ 7.25), severe visual or CNS symptoms
  1. Ethylene glycol
  • Found in antifreeze and brake fluids
  • Converted by alcohol dehydrogenase to glycolaldehyde which is metabolized to glycolic acid
  • Glycolic acid is primarily responsible for the anion gap metabolic acidosis; it is metabolized to multiple metabolites including oxalic acid
  • Oxalic acid forms calcium oxalate crystals in the kidney, brain and liver
  • Initial CNS changes suggestive of ethanol intoxication progressing over 9-12 hours to possible seizures, stupor, coma; toxicity may progress to pulmonary edema and myocardial dysfunction
  • Late toxicity is characterized by renal failure
  • Positive birefringent calcium oxalate crystals in the urine; often absent initially commonly described as “envelope-shaped”
  • May see hypocalcemia although not always present
  • Management:
    • Alcohol dehydrogenase inhibitors: Fomepizole or ethanol
    • Hemodialysis with same indications as methanol above
    • Thiamine and pyridoxine can be administered to decrease production of oxalic acid
    1. Isopropanol
  • Isopropyl (rubbing) alcohol
  • More intoxication/CNS depression but generally less severe sequlae than methanol and ethylene glycol 80% is absorbed from the stomach within 30 minutes and metabolized by alcohol dehydrogenase to acetone
  • Presentation: CNS depression, hypotension in severe cases, hemorrhagic gastritis/tracheobronchitis
  • Positive serum acetone and acetonuria
  • Anion gap metabolic acidosis is generally not a feature of isopropanol toxicity (unless you have significant hypotension with subsequent lactic acidosis)
  • Management:
    • Supportive care, including airway management
    • Alcohol dehydrogenase inhibitors are not indicated
    • Hemodialysis indicated for refractory hypotension or serum levels >400-500 mg/dL

Some Additional Points:

      • Lactic acid on lab analysis may be falsely elevated and vary depending on how the sample is analyzed. You will note that ABG lactic acid and serum lactic acid analyzed by lab are very different values, this is due to the fact that a metabolite of ethylene glycol’s metabolism has a very similar chemical structure to lactic acid, causing a falsely positive elevated lactic acid
      • The differential diagnosis of anion gap metabolic acidosis listed above is a limited list of the most commonly noted causes of AG metabolic acidosis; a comprehensive list is much broader
      • An osmolar gap >50 is highly suggestive of toxic alcohol ingestion; a level >100 is virtually pathognomonic—there is really nothing else that can cause such a severely elevated osmolar gap other than toxic alcohol

Case presented by Dr. GregnCassidy

Special thanks to Dr. Kashani for his guidance in preparing this case.

Euglycemic DKA

Hi all. I wanted to bring to your attention a great case. The case was a young woman with relative euglycemic diabetic ketoacidosis. This diagnosis used to be quite rare and associated with pregnancy or very poor PO intake. However, with the use of SGLT2 inhibitors (which this young woman was taking) the incidence is increasing. The diagnosis highlights some very important factors about the treatment of DKA:

  • Don’t just look at the blood sugar. Calculate your anion gap. Look at the bicarb. Calculate the strong ion difference. Check for ketones. A VBG is fine for a rough estimate of pH. If you really want to get fancy, an ABG will give you an accurate base deficit that can help you figure out (along with your lactic acid, strong ion gap, or delta-delta) exactly what else is going on with the patient in the setting of multiple competing metabolic processes. But that’s only if you want to get fancy. I think you can provide great initial resuscitation without it.
  • Remember why we do what we do in DKA and all the complications you can get from treatment. The treatment is based on exactly the same principles that guide the treatment of “regular” DKA. However, they are not starting at the exact same metabolically disturbed place as most patients do. They can be just as sick, if not more, but the initial treatment has to take into consideration exactly where they are in their metabolic disarray. Things to think about as you are coming up with a treatment plan:
  • These patients need fluid. Fluid will be your friend (more on that later)
  • These patients need glucose. From the start. For a glucose less than 100-125, consider starting D10 instead of D5.
  • They need glucose because they need insulin too. They still may have some relative insulin resistance so giving them glucose alone won’t help them if they cannot get the glucose into any cells. However, as you are already starting from a lower glucose, be very gentle. If you still bolus insulin in DKA (which I do- in selected cases- and would be glad to have conversation about whether we should or not at another time) do NOT bolus these patients. I don’t have great evidence as to where to start a drip so I pick a low number. Like 1 low. I can always move up. If anyone has a better scientific explanation on how to pick your infusion rate, I’d love to hear it.
  • They need insulin so you better be sure you aren’t going to cause a malignant arrhythmia if you give it to them. Make sure your potassium isn’t going to plummet when you start insulin. Rough guideline is to make sure it is >3.3 . This is true for all DKA.
  • They don’t have a sodium correction because the glucose is normal. If their sodium is already on the higher side (around >140), think of starting with ½ NS as your base.

The attending on the case did an excellent job with this patient. He focused on fluid and recognized her severe metabolic disturbance, despite the fact that her blood sugar was trying to hide it.

I’ve included two articles below. One is two case reports on euglycemic DKA and the other talks specifically about cases involving SGLT2 inhibitors. They aren’t the best articles I’ve ever read but they are more official than I am so felt I should include them. As a said, this is a relatively new class of medications and a relatively new phenomenon.


Euglycemic diabetic ketoacidosis: a diagnostic and therapeutic dilemma, EDM Case Reports, September 2017

Posted by:

Ruth Lamm, MD FACEP
Assistant Professor
Emergency Medicine
Critical Care Medicine
Saint Joseph’s Hospital Medical Center
lammr@sjhmc.org

AMA after Narcan – Is it safe?

In comes a 34-year-old male who is obtunded with pinpoint pupils and breathing at five times a minute; likely due to heroin abuse.  He wakes up after Narcan is appropriately administered, but now he wants to leave.  What is the risk of death if he leaves?  Do we restrain him against his will to monitor him for possible recurrent respiratory depression?

We have some pre-hospital literature that looked into this issue.  The studies looked at patients who refused care after pre-hospital providers administered Narcan for a suspected opiate overdose.  They then searched the death registry to see if those patients later died after refusing care (transport to the hospital).

Wampler et al. looked at 552 patients and found that no one died until at least 4 days later (1).  These deaths four days later were unlikely to be from the initial overdose.  A second study recently published in March of 2016 had 205 patients and showed only one death in 24 hours (2).  Two others died in the 30-day follow up period which again were not likely due to the initial overdose.  Combining the numbers from these two studies equates to 1/757 (0.13%) deaths.

There are limitations with all studies, but death seems unlikely after refusal of care post-narcan administration.  However, our practice should not change as it relates to monitoring patients for about 4 hours to those willing.  Recurrent respiratory depression is a real concern particularly seen in those patients who abuse long acting opiates.  Despite this, some patients who have the capacity to make decisions may not choose the wisest care plan and may leave AMA.  We must still make considerable attempts at providing substance abuse referrals and other appropriate resources as these patients are in great need of help.

Post by: Joe Bove  (@jjbove08)

  1. Wampler D, Molina D, McManus J, Laws P, Manifold C. No deaths associated with patient refusal of transport after naloxone-reversed opioid overdose. Prehosp Emerg Care. 2011;15(3):320-324.
  2. Levine M, Sanko S, Eckstein M. Assessing the Risk of Prehospital Administration of Naloxone with Subsequent Refusal of Care. Prehosp Emerg Care. March 2016:1-4.

Digoxin abortion gone awry….or did it?

Emergency medicine has to be one of the most diverse fields of medicine out there.  Each day is a whirlwind of activity and patients, ranging from cardiac arrests down to the broken fingernail.  Not only are we responsible for the most critically ill, the walking wounded and the patients that have nowhere else to go, but also are faced with the complications encountered in the outpatient setting.  This could be a patient fresh from the chiropractor that is having neck pain, can’t move their arm and now have a carotid dissection; or a patient from a outpatient surgi-center that had local anesthesia but is now seizing; or in the case below a patient that underwent an elective abortion and now is hypotensive and bradycardic.

A 19-year-old female at 20 weeks gestation who had just underwent part 1 of a two day late term elective abortion presents with a syncopal event about 2 hours after the procedure.  Her vital signs at the time were BP: 60/palp, HR: 40bpm, RR: 16, O2: 100% RA and T: 98.7.  After a liter of normal saline her blood pressure and heart rate both normalized (BP:120/70, HR:70s)

So what happened?  Since 2013 one of the day 1 medications of late term abortions is trans-vaginal Digoxin that is delivered either intrafetally or intraplacentally.  The dose is typically 1-3 mg and in this case the patient received a dose of 2 mg.  Initially they drew a dig level, so let’s think about this. You have a post procedural syncope, with a patient still in the clinic 2 hours after the treatment.  You would have to believe that they were concerned about sending her home, she is hypotensive and bradycardic.  Digoxin is used to increase inotropy, thus improving cardiac output. It is doubtful this young healthy female patient, would present with hypotension in this setting. Also the dig level was drawn within first 3 hours of administration and had a level of 5. As you know Dig has a large volume of distribution and levels should be drawn after 6 hours of administration. Also her symptoms improved with IVF, and the only thing they reported were questionable T-wave inversions in lateral leads as the only EKG abnormality, this is after her symptoms resolved. Dig toxicity can present with multiple EKG abnormalities: T-wave changes, short QT, St-scooping, AV blocking, VT, VF, and most commonly PVC’s, and various conduction abnormalities. The center did not transmit EKG.

Her Dig level before they gave her Digibind, was 1.3. The discussion consensus amongst the NYPCC toxicologists was clear on not giving Digibind in this setting; just observe the patient on tele, repeating EKG, and discharging the next morning.  The patient more likely was having anxiety around her procedure and suffered a vasovagal event, that improved with IVF. The patient was fine and went to clinic next day for termination of pregnancy.

There are plenty of complications that can occur after abortions, whether they are infections, retained products of conception, DIC, amniotic fluid embolisms and as described above, aberrant delivery of abortifacient medications.  Besides the historical use of mechanical means of fetal termination, there are pharmacologic medications as well; most commonly intracardiac KCl and intra-fetal/intra-amniotic digoxin.  As you might expect, delivery of these medications could inadvertently end up being maternally injected and will present as though they are hyperkalemic or having acute digoxin toxicity.  The management of both are the same as we typically would proceed with.  Just knowing that these are potential methods that are used for abortions may give you an extra consideration if one of these patients presents to your ED.

Post by: Dr. Daniel Poor, MD

Tox Box Journal Club

In this installment of the Tox Box Journal Club we are going over three articles reviewed at the NYC Poison Control Center in Manhattan last week.  Two of the articles discuss utility of lipid emulsion therapy in animal models and a third on the deleterious effects of methotrexate dosing errors in Australia.
Background: LAST = Local Anesthetic Systemic Toxicity is a well described phenomenon which can occur from accidental intravenous administration of anesthetics during peripheral nerve blocks or other procedures. Seizures are often described following accidental intravenous administration, which can then lead to cardiovascular collapse in the setting of severe acidosis and hypoxia. This study was designed to see if there exists a role for lipid emulsion therapy for LAST. Prior animal models did not account for the acidosis / hypoxemia that is known to occur, and this model was able to simulate these settings
Methods: 20 pigs separated into 2 groups of 10. All were anesthetized/paralyzed/intubated. Then infusions of levobupivicaine were administered to each at a dose of 3mg/kg, then five minutes of hypoventilation, then 1mmol/kg of lactic acid infusion (to simulate aforementioned settings). One arm was given Lipid emulsion, the other arm was given Ringer’s acetate. Mean arterial pressure / HR / EKG/QRS/ and plasma concentrations of the anesthetic were all monitored and compared. 
Results: The data show that there was no effect of lipid emulsion compared to that of the ringer’s acetate. QRS took similar amounts of time to narrow in both arms. Pharmacokinetics of Levobupivicaine were the same in both groups. 
Bottom Line: Although there have been case reports describing successful resuscitation of patients who suffer from LAST who were given lipid emulsions during resuscitation, this particular model which simulates acidosis and hypoxemia in pigs, does not support the use of lipid emulsion therapy for local anesthetic toxicity. There seems to be a growing body of lack of support based on this study and others like it. 
 
 
Background: Intravenous lipid emulsion (ILE) is a potential antidote for severe overdoses and its use in cocaine toxicity has been suggested; however, it is not well characterized. Its potential use as an antidote during cocaine toxicity was the focus of this study to see if cocaine-induced cardiac arrest in rats was able to be reversed using this therapy.
Methods: 12 rats were given lethal doses of cocaine IV over 30 seconds, and mechanical chest compressions were initiated once asystole was noted. One arm was given ILE, while the other arm was given a similar bolus rate of 0.9% NS. 
Results: The data show that ILE had no affect in the terminal outcome in cocaine-induced cardiac arrests in this particular rat model, suggesting that this is not an appropriate toxin/antidote pairing. Only 1 of 12 rats received ROSC and was found to be statistically not significant. This rat was in the ILE arm of the study.
Bottom Line:  This article demonstrates some potential design flaws including small sample size,  and withholding ACLS medications post cardiac arrest which potentially would have aided in resuscitation. 
This was a retrospective review article which sheds light upon the fatal errors which can occur as a result of accidental, improper dosing of methotrexate (MTX).  After looking at the Australian database for reported poisonings, errors occurred for a number of reasons and the ones most commonly identified were: 
  •  mistaking medication for another medication
  •  care-giver/nursing home error
  •  MTX was newly prescribed medication
  •  pharmacy dosing packet error
  •  misunderstood directions
  •  patient believing it would improve efficacy
  •  prescribing error by physician
  •  dispensing error
  •  labeling error 
As a result there were 22 deaths noted to be linked to MTX administration errors
Bottom Line:  These medication errors are not uncommon, and because MTX is a high risk medication which can become fatal if taken incorrectly, further care is warranted in dealing safely with this medicine. A multi-faceted approach should be considered and suggestions are still ongoing. Some recent suggestions have been to change packet size, to increase education/awareness, mandatory weekly dosing labeling on packaging, including software alerts for prescribers and dispensers
Post by: Dr. Ray Brancato (@drrayfields)

Octreotide for sulfonylurea poisoning

Newer second generation sulfonylureas are used extensively for treating type-2 diabetes mellitus (i.e. glyburide, glipizide, glimepiride and gliclazide). They are rapidly absorbed and reach peak plasma concentration typically within 2-4 hours; and have a duration of action up to 24 hours long. In 2010, the American Association of Poison Control centers reported nearly 4,000 cases of sulfonylurea exposures that led to no reported fatalities. Previous treatment has revolved around IV dextrose and glucagon for treatment of sulfonylurea associated hypoglycemia, but octreotide is another option for treating these exposures.

Mechanism of Octreotide and Sulonylureas

Sulfonylureas help to increase the amount of endogenous insulin release from the pancreatic beta cells. They bind to sulfonylurea receptors that are associated with ATP dependent potassium channels on the pancreatic beta cell membrane. By inhibiting potassium efflux, the membrane depolarizes causing influx of calcium and subsequent exocytosis of insulin. Octreotide counters this mechanism by closing the calcium channels after binding to somatostatin receptors, which prevents the secretion of the insulin.

Dosing

For adults we can use 50-100ug SC every 6-12h and for children 1-2 ug/kg SC up to 50ug q6-12h. Typically the patient will received 3 doses of octreotide as well as supplemental IV dextrose which can be gradually tapered off as tolerated. An extended length of observation may be needed for patients with renal impairment as sulfonylureas and insulin clearance will be impaired.

Check out The Poison Review for a couple posts on using octreotide for sulfonylurea poisoning here and here.

Post by: Terrance McGovern DO, MPH (@drtmcg13)