A bad trip… to the ICU – A case presentation and general overview of poisonous mushroom ingestion

A bad trip… to the ICU – A Resident Clinical Pearl  on poisonous mushroom ingestion

Scott Fenwick 

PGY-1 Family Medicine, Dalhousie University

Reviewed by: Liam Walsh, Clinical Pharmacist

Copyedited by: Dr. Mandy Peach

Case Presentation:

A 43yo otherwise healthy female presents to the ED with 30 hours of intractable nausea, vomiting, diarrhea, and diffuse crampy abdominal pain. 12 hours prior to the onset of these symptoms, she had foraged six wild mushrooms, fried them with butter, and ate them with her dinner. She had used a wild mushroom reference guide and thought these “pristine white” mushrooms would be a safe steak topping.

In the ED, she was alert and oriented with a GCS of 15 and no apparent encephalopathy. Her vitals were BP 109/68, P 93, T 37, RR 16, O2 97% RA. She was retching and vomiting clear emesis, which settled some with ondansetron 8mg IV. Clinically, she looked dehydrated but otherwise not toxic. Her abdomen was soft and diffusely tender. Cardiorespiratory exams were unremarkable. There were no skin findings.

A 1L bolus of normal saline was administered. Serum laboratory studies, drawn approximately 42 hours post-ingestion returned as follows:

Urinalysis showed trace blood, ketones and protein. ECG showed normal sinus rhythm.

The marked elevation in liver enzymes and abnormal coagulation studies were concerning for hepatocellular injury and fulminant hepatic failure. The local Internal Medicine consultant was contacted, and the patient was transferred to the ICU at the nearest liver transplant center.

In consultation with pharmacy and poison control, it was determined that the most likely offending mushroom was Amanita virosa, more commonly know as a Destroying Angel.

The patient was started on NAC, activated charcoal, penicillin G, cimetidine, vitamin C, and IV silibinin (milk thistle). Consideration was given to percutaneous cholecystostomy, as the toxin can accumulate in the gallbladder, but this was not anatomically feasible at the time.
Laboratory studies peaked at 72 hours post-ingestion as follows

Vitamin K was given to lower the INR. Creatinine continued to climb and was 835 prior to initiation of hemodialysis. Liver studies slowly trended downward with ALT 9774, AST 4586, and INR 1.7 at 96-hours post-ingestion. Ultimately, liver function values returned to normal and enzymes levels continued to trend downward—making liver transplant not necessary.

Overview of Toxic Mushroom Ingestion:

Epidemiology:

According to the 2019 Annual Report of the American Association of Poison Control Centers’ National Poison Data System, more than half of toxic mushroom ingestions occur in children under the age of 6. Serious toxicity and mortality, however, is more common in foraging adults, as they are more likely to consume larger quantities of a misidentified mushroom. Data for Atlantic Canada was difficult to obtain, but the Ontario Poison Centre received 72 calls related to mushroom exposures in September 2020, generally the peak month for exposures.

Poisoning Syndromes:

Only 20% of the time is the offending mushroom correctly identified, so we often rely on the clinical presentation to identify the likely species and relevant treatment. UpToDate lists 12 different mushroom toxins and 14 unique corresponding syndromes:

  • Acute gastroenteritis (<6hrs) without liver failure
  • Delayed gastroenteritis (6-12hrs) and delayed liver failure
  • Acute gastroenteritis and delayed renal failure
  • Hallucinogenic
  • CNS depression and excitation
  • Disulfiram-like reaction
  • Cholinergic excess
  • Delayed renal failure
  • Delayed rhabdomyolysis
  • Erythromelalgia
  • Delayed encephalopathy
  • Immune-mediate hemolytic anemia
  • Shiitake dermatitis
  • Allergic bronchioalveolitis

The syndrome from this case, bolded above, is delayed liver toxicity and delayed gastroenteritis.

This syndrome follows 3 phases:

  • Phase I: Dysentery – nausea, vomiting, diarrhea (6-24hrs post-ingestion)
  • Phase II: Apparent recovery (24-36hrs post-ingestion)
  • Phase III: Fulminant hepatic and multisystem organ failure (48-96hrs post-ingestion)

Poisonous Mushrooms in New Brunswick:

The New Brunswick Museum has compiled a catalog of the mushroom species discovered in the province. One of the deadliest mushrooms in the province is the Destroying Angel. This nickname refers to a group of mushroom species under the genus Amanita. Amanita virosa is commonly found in New Brunswick and Nova Scotia. They are pristine white and often located in wooded areas or next to trees/shrubs in suburban areas. They are most prevalent in the summer and fall.

In their button stage, Destroying Angels can be confused with white mushrooms that you might buy at the grocery store. Destroying Angels produce an amatoxin—a selective inhibitor of RNA polymerase II, leading to an interruption in protein synthesis and cell death. Amatoxins are especially toxic to the GI tract, liver and kidneys.

Notably, in the NB Museum catalog, there are no reports of Amanita phalloides, aka the Death Cap, in New Brunswick. In Canada, they are more commonly found in British Columbia.

EM Approach:

History:

  1. What did they look like? Ask for photos from the patient’s phone or samples if they have them. Identification assays are available but not always useful in the acute setting.
  2. Were the mushrooms collected in a field or along/underneath trees? Many toxic mushrooms are in wooded areas.
  3. How many types of mushrooms were ingested?
  4. How long after ingestion did symptoms develop? Less than 6hrs is associated with lower risk of—but does not exclude—potentially lethal ingestion.
  5. How much was eaten? Were there multiple times of ingestion?
  6. Did others eat the mushrooms? If so, do they have similar symptoms?

Physical Exam:

  • Assess hydration status
  • Assess for encephalopathy or other signs of fulminant hepatic failure

Laboratory studies:

Treatment:

  • Ondansetron for N/V, do not use anti-diarrheal agents
  • IVF for dehydration and electrolyte abnormalities
  • If a serious ingestion cannot be excluded, patients should be admitted for 24-48hrs for observation and serial bloodwork

Evidence-based recommendations for suspected amatoxin poisoning:
o Multiple dose activated charcoal: 0.5g/kg (max 50g) q4h for 4 days post-ingestion.

o Silibinin: loading dose of 5 mg/kg IV, followed by a continuous infusion at a dose of 20 mg/kg/day for 6 days or until clinical recovery.

If IV silibinin is not available, oral milk thistle capsules (Silymarin) are an effective alternative. The initial dose is 50-100mg/kg q8h, and titrated up to 200mg/kg q8h as tolerated, with a maximum single dose of 2-3g. IV Silibinin is available only through Health Canada’s Special Access Program. Pharmacy should be contacted early to assist with this process if it’s being considered.

o Penicillin G: 300,000 to 1,000,000 units/kg/day given as a continuous IV infusion. A small amount of research shows no benefit to adding this if IV silibinin is available. If penicillin allergy, consider ceftazidime 4.5 g every 2 hours.

o NAC protocol: initial loading dose of 150 mg/kg (max 10g), next a 4-hour infusion at 12.5 mg/kg/hr, then a 16-hour infusion at 6.25 mg/kg/hr. The 16-hour dose may be repeated if significant hepatic dysfunction persists.

o Cimetidine: 300 mg IV every 8 hours until clinical improvement (evidence in animal studies only)

o Vitamin C: 3 g IV daily until clinical improvement (evidence in animal studies only)

o Dextrose for hypoglycemia

o Lactulose for hyperammonemia

o Vitamin K +/- FFP for coagulopathy

o Dialysis for AKI

o Early consultation with liver transplant center

  • Treatments for other mushroom poisoning syndromes can be found in this chart

Bottom Line:

Ask if the patient has photos of the mushrooms on their phone, or if they can describe their appearance. Call local poison control with this information.

Obtain a clear history to determine the interval between time of ingestion and time of symptom onset. Acute gastroenteritis onset (<6hrs from ingestion) is associated with favourable outcomes, and delayed gastroenteritis (usually 6-12hrs from ingestion) is more likely to have liver and/or renal failure.

Liver studies may be normal until 24-36 hours and generally peak at 72-96 hours post-ingestion.

Early treatment and consultation/transfer to a liver transplant center is imperative.

 

References:

Cover photo: https://www.deviantart.com/dreadillustrations/art/Poison-Mushrooms-774297817

Gummin, D. D., Mowry, J. B., Beuhler, M. C., Spyker, D. A., Brooks, D. E., Dibert, K. W., Rivers, L. J., Pham, N., & Ryan, M. L. (2020). 2019 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 37th Annual Report. Clinical toxicology (Philadelphia, Pa.)58(12), 1360–1541. https://doi.org/10.1080/15563650.2020.1834219

Nelson, L. S., Howland, M. A., Lewin, N. A., Smith, S. W., Goldfrank, L. R., Hoffman, R. S., & Flomenbaum, N. E. (2019). Goldfrank’s toxicologic emergencies (11th ed.). Mc Graw Hill Education.

Shannon, M. (2007). Haddad and Winchester’s clinical management of poisoning and drug overdose (4th ed.). Saunders.

NB Museum Mushroom Checklist: http://website.nbm-mnb.ca/mycologywebpages/Checklists/NBMushrooms/NBMushroomChecklist.html

Tavassoli, M., Afshari, A., Arsene, A. L., Mégarbane, B., Dumanov, J., Bastos Paoliello, M. M., Tsatsakis, A., Carvalho, F., Hashemzaei, M., Karimi, G., & Rezaee, R. (2019). Toxicological profile of Amanita virosa – A narrative review. Toxicology Reports, 6, 143–150. https://doi.org/10.1016/J.TOXREP.2019.01.002

Amanita virosa photo: https://www.tehrantimes.com/news/423947/Mushroom-poisoning-kills-18-in-Iran

White mushroom photo: https://www.stockfood.com/images/00395464-Several-button-mushrooms

Amanita phalloides photo: http://www.bccdc.ca/about/news-stories/stories/2020/death-cap-mushrooms-make-fall-appearance-in-urban-areas

 

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A Biopsychosocial Approach to Epigastric Pain

A Biopsychosocial Approach to Epigastric Pain – A Medical Student Clinical Pearl

Gabrielle Hibbert, Med III

Dalhousie Medicine New Brunswick

Reviewed by Dr. Jay Hannigan

Copyedited by Dr. Mandy Peach

Case

A 22 year old male presented to the ER with a 6-week history of epigastric pain. The patient described the pain as a burning sensation radiating to his throat and RUQ. The pain was constant, exacerbated post-prandially, and associated with nausea and vomiting. He denied any hemoptysis, hematochezia, melena, dysphagia, odynophagia, symptoms of extra-esophageal reflux, or dyspepsia. He reported having a poor appetite associated with a twenty-pound weight loss. Review of systems was otherwise negative. Pantoprazole recently prescribed by his GP had not improved his symptoms. He denied using NSAIDs. He reported experiencing a lot of anxiety recently due to relationship conflicts with his partner and inability to access counselling services. He was scheduled to have an outpatient ultrasound of his gallbladder.

Past medical history: bipolar disorder, general anxiety disorder, depression, and tonsillectomy

Medications: olanzapine odt, citalopram, lamotrigine, and pantoprazole

Social: The patient worked at American Eagle, and he lived with his partner, his partner’s parents, and their 18-month-old son. He smoked one gram of Marijuana per day, vaped daily, and occasionally consumed alcohol. He was an ex-smoker and had a history of abusing cocaine, LSD, and crystal meth but had not used in three years.

Physical exam: The patient was afebrile, and his other vitals were within normal limits. He looked well and was in no visible distress. He had some mild epigastric tenderness to palpation. Cardiac, respiratory, and abdominal exam were unremarkable.

Investigations

CBC, electrolytes, LFTs, and TSH recently ordered by his GP were within normal limits. Serology testing for celiac disease was negative. CRP was <0.6.

The Biopsychosocial model

The biopsychosocial model illustrated in Figure 1 was introduced in 1977 by the American Psychiatrist George Engel1. He stated that “to provide a basis for understanding the determinants of disease… a medical model must also take into account the patient, the social context in which he lives, and the complementary system devised by society to deal with the disruptive effects of illness”1.

Figure 1. The Biopsychosocial model. Figure modified from 2.

The diathesis-stress model, proposed by Spielman and colleagues in 1987, illustrates how psychological, biological, and social factors contribute to the development and maintenance of disease3. An example of this model is shown in Figure 2.

Figure 2. Summary of potential predisposing, precipitating, and perpetuating factors across biopsychosocial domains3

 

Gastroesophageal Reflux Disease (GERD)

Gastroesophageal reflux occurs when there is inappropriate relaxation of the lower esophageal sphincter (LES) or delayed gastric emptying4. Multiple factors such as hiatal hernias, increased intraabdominal pressure, and certain drugs can contribute to this pathogenesis5. Altered processing of signals from the esophagus leading to hypersensitivity has also been linked to the pathogenesis of reflux6.

As illustrated in Figure 3, the bidirectional communication between the enteric nervous system and central nervous system is termed the “brain–gut axis” 7. Neurotransmitters involved include endogenous opioids, endocannabinoids, and serotonin6. These neurotransmitters are affected by stress and anxiety6. Dysregulation of the brain-gut-axis has been proposed to play a role in physical symptoms commonly reported by individuals with anxiety such as nausea, diarrhea, and abdominal pain7.

Figure 3. The brain gut axis. Figure modified from8.

 

Typical symptoms of gastroesophageal reflux include regurgitation and pyrosis4. Lifestyle modifications listed in Figure 4 and/or a short trial of a medication such as a proton pump inhibitor as illustrated in Figure 5 are reasonable first step in the management of patients with typical symptoms9.

Figure 4. Lifestyle modifications for GERD 11

Figure 5. Pharmacological therapy of GERD10

 

Atypical symptoms of gastroesophageal reflux include chest or epigastric pain, water brash, satiety, burping or hiccups, bloating as well as nausea and/or vomiting4.

Symptoms of extra-esophageal reflux include chronic cough, asthma, sore throat, hoarseness, and sinus or pulmonary problems4.

Alarm symptoms include dysphagia, odynophagia, epigastric mass, unexplained weight loss, as well as hematemesis, anemia, or other signs of upper gastrointestinal bleeding4.

Alarm symptoms, extra-esophageal reflux symptoms, or atypical symptoms raise the possibility of other diseases such as oesophagitis, peptic stricture or ulcer, or cancer and warrant further investigations11.

 

Back to our case

 

Impression: 22 year old male with a 6 week history of constant epigastric pain exacerbated post-prandially and associated with pyrosis, nausea, and vomiting. No alarm symptoms are present.  Physical exam and investigations were normal. Patient reported recent stressors exacerbating his GAD.

 

Biological factors:

  • Anxiety and bipolar illness since early teens
  • Substance abuse

Social factors:

  • Relationship conflicts
  • Stressful home environment
  • Responsibility of caring for his son

Psychological factors:

  • Worsening anxiety due to loss of counselling services and relationship conflits.
  • Anxiety/stress due to the Covid 19 pandemic

 

Abdominal pain

Abdominal pain represents 5-10% of emergency department visits13. About 25% of patients discharged from the emergency department receive a diagnosis of unspecified abdominal pain while 35- 41% of patients admitted to hospital receive this diagnosis13. Abdominal pain can be challenging to diagnose because it has a broad differential13.  Patients with recurrent abdominal pain are not exempt from a medical emergency so that must always be ruled out; however, repeating interventions or ‘giving a diagnosis’ of medically unexplained symptoms may perpetuate ongoing distress that ‘something” is being missed12. Addressing any psychological and social factors that may be contributing or exacerbating the pain could help relieve symptoms or increase the efficacy of ongoing treatment13.

Concluding management:

  • Compassionately acknowledged that the pain he is experiencing is distressing
  • Reassured him that there is no evidence of a medical emergency
  • Explained GERD and factors that are likely exacerbating his symptoms
  • Lifestyle modifications as in Figure 4
  • Other avenues for counselling services
  • Pantoprazole twice daily
  • Return to the ER if experiencing alarm symptoms
  • Follow up with GP

 

References

  1. Farre, A., & Rapley, T. (2017). The new old (and old new) medical model: Four decades navigating the biomedical and psychosocial understandings of health and iIllness. Healthcare (Basel, Switzerland)5(4), 88. https://doi.org/3390/healthcare5040088

 

  1. Verril-Schurmanj., & Friesen, Craig, A. (2013, November 6). Inflammation and the Biopsychosocial Model in Pediatric Dyspepsia, Dyspepsia. Advances in Understanding and Management, Eldon Shaffer and Michael Curley, IntechOpen. https://doi.org/ 10.5772/56635. Retrieved July 2, 2021, from https://www.intechopen.com/books/dyspepsia-advances-in-understanding-and-management/inflammation-and-the-biopsychosocial-model-in-pediatric-dyspepsia

 

  1. Wright, C. D., Tiani, A. G., Billingsley, A. L., Steinman, S. A., Larkin, K. T., & McNeil, D. W. (2019). A framework for understanding the role of psychological processes in disease development, maintenance, and treatment: The 3P-Disease Model. Frontiers in Psychology,10, 2498. https://doi.org/10.3389/fpsyg.2019.02498

 

  1. Vakil, N., van Zanten S., V., Kahrilas, P., Dent,J., Jones, R., Vakil,N.,… Zapata, C. (2006). The Montreal definition and classification of gastroesophageal reflux disease: A global evidence-based consensus. American Journal of Gastroenteroly, 101(8),1900-1920. https://doi.org/10.1111/j.1572-0241.2006.00630.x

 

  1. Mikami, D., J, & Murayama K., M. (2015). Physiology and pathogenesis of gastroesophageal reflux disease. Surgical Clinics of North America, 95(3), 515-525. https://doi.org/10.1016/j.suc.2015.02.006

 

  1. Tack, J., & Pandolfino, J. E. (2018). Pathophysiology of Gastroesophageal Reflux Disease. Gastroenterology, 154(2), 277-288. https://doi.org/10.1053/j.gastro.2017.09.047

 

  1. Martin C., R., Osadchiy, V., Kalani, A., & Mayer, E., A. (2018). The Brain-Gut-Microbiome Axis. Cell Mol Gastroenterol Hepatol, 6(2):133-148. Doi: 10.1016/j.jcmgh.2018.04.003.

 

  1. Bajic, J., E., Johnston, I., N., Howarth, G., S., & Hutchinson, M., R. (2018) From the bottom-up: Chemotherapy and gut-brain axis dysregulation. Front. Behav. Neurosci. 12:104. doi: 10.3389/fnbeh.2018.00104

 

  1. Smith, L. (2005). Updated ACG guidelines for diagnosis and treatment of GERD. American Family Physician, 71(12), 2376-2382. Retrieved July 2, 2021, from https//www.aafp.org/afp/2005/0615/p.2376.html

 

  1. Zeid,, Y., & Confer, J. ( 2016). Standards of care for GERD.  S. Pharmacists, 41(12), 24-29. Retrieved July 2, 2021, from https:/www.uspharmacist.com/article/standards-of-care-for-gerd

 

  1. Alberta Health Services. GERD primary care pathway. April 2020. Retrieved July 2, 2021, from https://www.albertahealthservices.ca/assets/about/scn/ahs-scn-dh-pathway-gerd.pdf

 

  1. Kendall, J., L., & Moreira, M. (2020). Evaluation of the adult with abdominal pain in the emergency department. Retrieved July 2, 2021, from https://uptodate.com/contents/evaluation-of-the-adult-with-abdominal-pain-in-the-emergency-department_

 

  1. Daniels, J., Griffiths, M., & Fisher, E. (2020) Assessment and management of recurrent abdominal pain in the emergency department. Emergency Medicine Journal, 37, 515-521. https://doi.org/1136/emermed-2019-209113
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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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