Euglycemia DKA – don’t miss it!

EM Reflections May 2021 – Euglycemia DKA

Big thanks to Dr. Paul Page for leading this month’s discussions.

All cases are imaginary but highlight important learning points.

Authored and Copyedited by: Dr. Mandy Peach

Case

A 65 yo female presents with n/v ongoing for 2 days. She feels fatigued and has not been able to keep down fluids. She denies diarrhea. She has no history of abdominal surgeries. She does describe increasing productive cough that preceded the vomitting. She denies fever, but does complain of shortness of breath.

PMH: DLP, DM, GERD
Medications: Atorvastatin, Empagliflozin, Pantoprazole

Vitals: BP 104/66 HR 110 RR 22 O2 96% RA T 37.8 gluc 7.2

On exam there is obvious dehydration, and she seems fatigued with her eyes closed through most of the exam. She does respond to speech. The abdominal exam is unremarkable for focal tenderness. There are expiratory crackles heard at the R lung base.

You order a portable CXR1 and baseline labs including a VBG and lactate.

You suspect pneumonia with dehydration. You initiate a 1L NaCL bolus and order antibiotics.

You continue seeing other patients when you get a call from the nurse – the VBG is back for the patient.
They appear to have a metabolic acidosis with a pH of 7.10 and an anion gap of 14. The lactate appears surprisingly normal. The patient hasn’t made any urine yet for a sample.

What is the differential for anion gap metabolic acidosis2?

Going through the ‘MUDPILES’ mnemonic and revisiting the history nothing seems to fit. But there is a history of DM.

What red flag should trigger you to consider DKA despite the normal glucose?

The patient is on Empagliflozin. This is a SGLT-2 inhibitor. Patient on these medications are at risk of Euglycemic DKA.

In Euglycemia DKA there is a “relative carbohydrate deficiency state with normalization of serum glucose and concomitant elevation of counter-regulatory stress hormones. This leads to free fatty acid catabolism and ketone production.” 3

In any patient on a “zin” consider euglycemic DKA.

You order a serum ketone as well as β-hydroxybutyrate.

Clinically how do patients present with euglycemic DKA3?

Nausea/vomiting, malaise, shortness of breath – the differential is huge for this presentation. Again, look at the medication list for any diabetic patient. If you see a ‘zin’ – consider euglycemic DKA.

Alternatively if you order a gas and incidentally find anion gap metabolic acidosis in a diabetic patient consider ordering ketones/ β-hydroxybutyrate.

What about if this patient was an alcoholic? How would these complicate the diagnosis4?

Alcoholics can also present quite similarly with alcoholic ketoacidosis – nausea/vomiting, malaise, and similar lab findings. Other than the history one distinguishing characteristic is that alcoholic ketoacidosis tends to have frankly low blood glucose.

Are the triggers for euglycemic DKA any different3?

No, triggers for DKA are the same. Essentially any physiological stress.

A quick way to remember is the 5 I’s

Infection pneumonia, UTI, skin, abdominal
Infarction MI, CVA, bowel infarction
Infant on board pregnancy
Indiscretion dietary nonadherence
Insulin deficient insulin pump failure or non-adherence

Infection and insulin deficient secondary to non-adherence or inappropriate dosing are the most common causes.

I would also consider adding a 6th I – iatrogenic meaning drugs

What drugs commonly trigger DKA3?
– Glucocorticoids
– Diuretics
– Atypical antipyschotics

Are there any patients at risk of euglycemic DKA other than those taking the ‘zins’3?
Yes!

  • Pregnant patients -due to high placental glucose use they can have a relative euglycemia
  • Chronic pancreatitis
  • Bariatric surgery patients – absorption issues

Your patient was straight cathed for a small amount of urine which shows ketones. The beta-hydroxybuterate is also now back and is positive. You confirm euglycemic DKA.

You grab your nearest DKA algorithm to review with the nurses and begin treatment.

Besides ease of use, what are the clinical reasons for using a standardized DKA order set?
Standardized, evidence based DKA order sets have been shown to decrease time to closure of anion gap, reduce length of hospital admission and minimize complications during treatment3.

You get started with the treatment as per the order set. While treatment is commenced you sit down with your medical student and review the goals of DKA3.

Correct fluid deficits – patients in DKA get a osmotic diuresis from hyperglycemia, or dehydration from underlying illness. You want to restore volume before initiating insulin. This improves organ perfusion, renal function and lowers lactate formation.

What fluid to use? Initially NS or RL, but after initial resuscitation consider switching to RL to avoid hyperchloric acidosis associated with large volume resuscitation.

Normal or high corrected sodium? Switch to 0.45% NaCL

1 bag vs 2 bag? Having 2 bags of half NS (one with D10W) both adjusted to maintain maintenance of 250cc/hr and keep euglycemic has been shown to have better outcomes: less hypoglycemia, faster closure of anion gap and less IV insulin required.

Replacement of potassium – patients in DKA have large total body potassium deficits, however due to volume contraction and acidosis the potassium is often read as normal or high.

Starting the insulin infusion will also shift potassium intracellularly. Therefore potassium should be replaced before starting insulin therapy. See the table below for guidance3.

Closure of the anion gap to stop ketone production – the issue with DKA is not necessarily the hyperglycemia, it is the ketoacidosis from low circulating insulin. After fluid resuscitation and potassium replacement, the goal is to treat the excess of serum ketones by providing insulin. This corrects the metabolic acidosis.

Avoiding hypoglycemia secondary to insulin as you correct the acidosis is pertinent. Goal is 12-14mmol/L. Once glucose drops before 14 add D5 infusion to avoid hypoglycemia as you continue the insulin infusion.

Do not stop the insulin infusion if glucose drops! It is needed to correct the ketoacidosis. If it is stopped ketone production will quickly increase again.

Gluc really low? Decrease the insulin infusion by 50%, give an amp of D50 and switch to D10.

Treat underlying precipitant.

 

It’s been a couple of hours. The medicine team is busy with unwell patients on the floor and you are still managing the DKA patient. You have been reassessing gases and the anion gap is not closing.

What could be going on3?
– Inadequate fluid resuscitation
– Inadequate insulin dose
– Malfunction of insulin infusion
– Underlying diagnosis contributing to anion gap hasn’t been addressed.

You reevaluate fluid status and the patient has not made any additional urine other than the small amount attained on straight cath.
You decide to repeat a 500cc bolus to address dehydration as well as increase the insulin infusion.

Could this patient be at risk of cerebral edema3?
Certainly, over-resuscitating too quickly can put patients at risk of cerebral edema. However, our patient has clinical and laboratory signs that they are still fluid deplete.

When replacing fluids consider isotonic fluids ie. D5 RL to decrease the risk.

Avoid lowering serum osmolality too quickly (ie. No more than 3mmol/kg/hr) or decreasing sodium by > 10mmol/L in 24 hours.

The sodium will often increase initially due to glucose moving intracellularly – this is not actually a measure of serum sodium – do not treat.

Admissions are backed up in the ED and you’re still caring for the patient at the end of your shift. You handover to the senior resident working with the incoming staff.

What are your goals for resolution? 3

Glucose < 11.1 AND 2 of:
– Normalization of anion gap
– Venous pH > 7.3
– Serum bicarbonate ≥15 mEq/L

At this point the patient should be mentally alert and able to eat. At this point, switch to their subcutaneous insulin dose at home. Ensure their basal insulin is also administered.

There should be an overlap of 2-4 hours before stopping the insulin infusion – if insulin infusion is abruptly stopped before administering subcutaneous insulin the patient can quickly return to an acidotic state.

What if this is the first presentation of DM and they are not on any treatment at home5?

“In patients with new-onset type 1 diabetes who have presented with DKA, an initial total daily dose (TDD) of 0.5 to 0.8 units/kg units of insulin per day is reasonable, until an optimal dose is established.

Approximately 40 to 50 percent of the TDD should be given as a basal insulin, either as once- or twice-daily U-100 glargine or detemir, or as twice-daily intermediate-acting insulin (NPH).

The long-acting insulin can be given either at bedtime or in the morning; the NPH is usually given as approximately two-thirds of the dose in the morning and one-third at bedtime. The remainder of the TDD is given as short-acting or rapid-acting insulin, divided before meals.”

The resident astutely asks about respiratory status, and if they were to decompensate what would be suggested management3?
Bottom line – avoid intubation DKA patients if possible

  • These patients hyperventilate to try and correct the acidosis, so the ventilator must also match this large volume and RR. This puts them at risk of ventilator injury and ARDS

  • Because they need to compensate with hyperventilation if there is a prolonged period of apnea from complicated intubation the acidosis can significantly worsen, putting them at high risk for circulatory collapse

But if you have to intubate, some pointers:

  • Like any patient, resuscitate first
  • If you paralyze – bag the patient throughout.
  • Consider anti-emetic
  • If the serum bicarb is < 10, considering giving an amp of bicarb
  • Once tubed the vent settings should have a high tidal volume (8cc/kg) and high respiratory rate (24-28)

How about alternative therapies if the patient is tiring, like Bipap?

DKA patients often have gastroparesis so are high risk of aspiration and emesis. Ideally, BiPap should be avoided.
If there are oxygenation issues consider high-flow nasal cannula.

The patient has resolution of their DKA within the ED and is finally admitted for treatment of the underlying cause – community acquired pneumonia.

 

References and further reading

  1. https://radiopaedia.org/cases/right-lower-lobe-consolidation-pneumonia
  2. https://www.picmonic.com/pathways/physician-assistant/courses/standard/pathology-10894/acid-base-disorders-39738/normal-gap-metabolic-acidosis_259
  3. Helman, A. Baimel, M. Sommer, L. Tillmann, B. Episode 146 – DKA Recognition and ED Management. Emergency Medicine Cases. September, 2020. https://emergencymedicinecases.com/dka-recognition-ed-management. Accessed [July 16, 2021
  4. Helman, A. Himmel W. Best Case Ever 58 Euglycemic DKA. Emergency Medicine Cases. June 2017. https://emergencymedicinecases.com/euglycemic-dka/. Assessed July 19, 2021.
  5. Hirsch I, Emmett M. 2020. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment. https://www.uptodate.com/contents/diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults-treatment?search=dka&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H23160691
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Cannabis Hyperemesis Syndrome – a hot topic!

Cannabis Hyperemesis Syndrome – A Medical Student Clinical Pearl

Alyssa Dickinson, Med II
Dalhousie Medicine New Brunswick, Class of 2023

Reviewed by Dr. Erin Slaunwhite

Copedited by Dr. Mandy Peach

Case presentation:

A 24yo male, Mr. X, presents to the emergency department with a 12-hour history of sudden onset vomiting. The vomiting came on without warning and was associated with epigastric abdominal pain and sweating. Mr. X took one Gravol at home but was unable to keep it down. He explains that taking a hot shower will briefly relieve his symptoms, and he has already taken four showers today. He is otherwise well, and denies recent fever/chills, chest pain, shortness of breath, or changes in bowel/bladder patterns.

Mr. X has no relevant past medical history and is not currently taking any medications. He denies drinking alcohol but states that he smokes three joints of cannabis daily, and has done so for the past 3 years. He does not use any other recreational drugs.

On physical exam, Mr. X appeared pale and was actively vomiting. All vitals were within normal limits. Cardio, resp, abdo, and neuro exams were all normal.

Cannabis Hyperemesis Syndrome:

Cannabis is the most commonly used recreational drug in the world, with the highest prevalence among those ages 18-25 years old.1,2 Although sometimes used as an anti-emetic, chronic cannabis use has been associated with paradoxical hyperemesis, which has been described as cannabis hyperemesis syndrome (CHS).3 CHS is a chronic functional gastrointestinal disorder that presents with episodic hyperemesis following prolonged cannabis use.4 Most cases of CHS present within 1-5 years of regular weekly cannabis use, although the pathophysiology remains unclear.1 Unfortunately, CHS is underrecognized and underreported, and as a result many patients experience a delay in diagnosis up to 9 years.1,2,5

The clinical course of CHS can be divided into three phases:

  • prodromal,
  • hyperemetic, and
  • recovery phase.2,5

Although similar in presentation, CHS is different then cyclic vomiting syndrome (CVS), as categorized by the Rome IV classification for functional disorders.4

Features that may help distinguish CHS from CVS include the following:
– All patients with CHS will have a history of regular weekly cannabis use, while those with CVS may or may not use cannabis products.

  • CVS may be a manifestation of migraine diathesis, and therefore is associated with a high prevalence of migraines or family history of migraines. CHS is not associated with headaches and will not respond to migraine-abortive medications.6

  • CVS patients are more likely to have psychological comorbidities including depression and anxiety.2

  • Gastric emptying rates in CVS are often accelerated, while in CHS they are more likely to be delayed.2

  • Relief with hot showers is present in 91% of patients with CHS, and only 50% of patients with CVS.1,4

With increasing prevalence of cannabis use, the incidence of CHS is likely to rise.7 It is therefore important to ask all patients with otherwise unexplained cyclic vomiting about cannabis use and compulsive bathing.5

Initial Assessment:

The differential diagnosis for CHS is broad, so it is therefore important to collect a comprehensive history and perform screening tests to rule out other potential causes.

Investigations:

Screening tests include routine blood work with a pregnancy test, if applicable. Further investigations vary based on each individual presentation.

Red flag symptoms that warrant further investigations to rule out alternate diagnoses include hematemesis, neurologic findings on exam, and abdominal tenderness.2

 

Diagnosis:

In most cases of CHS, all laboratory, radiographic, and endoscopic results will be negative.1 Diagnosis therefore is based on the following clinical criteria, retrieved from Simonetto et al (2012):

Note: CHS is a diagnosis of exclusion – all other pathologies must be ruled out.

 

Management:

The mainstay of treatment for CHS includes supportive therapy, with or without hospitalization. If volume depletion is present, immediate IV fluid resuscitation is warranted.2 The patient’s condition is expected to resolve within 12-24 hours of fluid replacement therapy.3

 

The following is the Emergency Medicine Saint John algorithm for CHS:

Notes on Symptom Management:

  • The most effective treatment for CHS symptoms is a warm bath or shower.2 This has been shown to quickly settle nausea, vomiting, and abdominal pain, although these effects do not persist. Symptom relief is temperature dependent, with hotter water producing a greater effect.3
  • Ruberto et al (2020) demonstrated superiority of IV haloperidol (one time dose of 0.05mg/kg) over ondansetron in improving symptoms of nausea, vomiting, and abdominal pain. Patients who received haloperidol also had a shorter discharge time from the ED and had fewer return visits to the ED for ongoing symptoms.
  • Traditional anti-emetic therapy such as 5-HT3 receptor antagonists or H1 receptor antagonists may used in addition to haloperidol, although most patients will have little to no response.2

 

Prevention of Recurrence:

  • Cannabis cessation is the only proven treatment for CHS.
  • Patients should be counselled on cannabis cessation, ideally from a specialized addiction team member.9 They may also benefit from outpatient treatment options including cognitive behavioural therapy and/or motivational enhancement therapy.2

 

Case Conclusion:

Mr. X was started on IV fluids to restore volume. He was also given capsaicin 0.075% topical cream and haloperidol (0.05mg/kg) for symptom management. His symptoms resolved within 4 hours and he was discharged home with a plan for outpatient follow-up to support cannabis cessation.

 

Want a deeper dive into CHS? Visit this medical student clinical pearl

References:

  1. Simonetto, D. A., Oxentenko, A. S., Herman, M. L., & Szostek, J. H. (2012, February). Cannabinoid hyperemesis: a case series of 98 patients. In Mayo Clinic Proceedings(Vol. 87, No. 2, pp. 114-119). Elsevier.
  2. Galli JA, Sawaya RA, Friedenberg FK. Cannabinoid hyperemesis syndrome. Curr Drug Abuse Rev. 2011;4(4):241-249. doi:10.2174/1874473711104040241
  3. Allen JH, de Moore GM, Heddle R, Twartz JC. Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Gut. 2004;53(11):1566-1570. doi:10.1136/gut.2003.036350
  4. Venkatesan T, Levinthal DJ, Li BUK, et al. Role of chronic cannabis use: Cyclic vomiting syndrome vs cannabinoid hyperemesis syndrome. Neurogastroenterology & Motility. 2019;31(S2):e13606. doi:https://doi.org/10.1111/nmo.13606
  5. Soriano-Co M, Batke M, Cappell MS. The cannabis hyperemesis syndrome characterized by persistent nausea and vomiting, abdominal pain, and compulsive bathing associated with chronic marijuana use: a report of eight cases in the United States. Dig Dis Sci. 2010;55:3113–9.
  6. Batke, M., & Cappell, M. S. (2010). The cannabis hyperemesis syndrome characterized by persistent nausea and vomiting, abdominal pain, and compulsive bathing associated with chronic marijuana use: a report of eight cases in the United States. Digestive diseases and sciences55(11), 3113-3119.
  7. Ruberto, A. J., Sivilotti, M. L., Forrester, S., Hall, A. K., Crawford, F. M., & Day, A. G. (2020). Intravenous Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized, Controlled Trial. Annals of Emergency Medicine.
  8. Dezieck L, Hafez Z, Conicella A, et al. Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series. Clinical Toxicology. 2017;55(8):908-913. doi:10.1080/15563650.2017.1324166
  9. Pélissier F, Claudet I, Gandia-Mailly P, Benyamina A, Franchitto N. Cannabis Hyperemesis Syndrome in the Emergency Department: How Can a Specialized Addiction Team Be Useful? A Pilot Study. The Journal of Emergency Medicine. 2016;51(5):544-551. doi:10.1016/j.jemermed.2016.06.009
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Canada’s Top 40 Research Hospitals – Saint John Regional Hospital

Canada’s Top 40 Research Hospitals – Saint John Regional Hospital

Incorporating novel research into everyday clinical practice to improve patient care within NB – that’s the goal of Dr. Kavish Chandra, Director of Research in Emergency Medicine in Saint John, NB. The Emergency Department at Saint John Regional Hospital has been a leader in research – from medical student projects to nationally recognized trials –  research is an integral part of the department and the hospital.

 

Interested in what projects are ongoing that are changing how we practice medicine? Check out our Research Projects.

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Congratulations Dr. Melanie Johnston – Resident Research Award Winner

Congratulations to our own Dr. Melanie Johnston, a second year resident in the FMEM Program here in Saint John. Dr. Johnston was the recipient of The Dr. Douglas E. Sinclair Award in Emergency Medicine Research for her research project entitled “- Impact of shift Trial on Overnight Patient Flow at the Saint John Regional Emergency Department.” This award is presented by the Dalhousie Department of Emergency Medicine to the most significant research project presentation at the annual Emergency Medicine Research Day.

It is judged on the following criteria: background and research methodology, overall presentation, critical appraisal and appropriateness to emergency medicine and clinical practice.

Congratulations Dr. Johnston!

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