Local Anaesthetic Toxicity (LAST)

Local Anesthetic Toxicity (LAST)

Think about the number of times a month you use a local anaesthetic; maybe not every day, but I know there are a lot of emergency department shifts when I use a local anaesthetic. The uses and applications for local anaesthesia abound: wound care and laceration closure, pain control with painful procedures like a paracentesis or lumbar puncture, and targeted regional anaesthesia blocks after a broken hip. It is important to know and understand a bit more about this commonly used class of drug given how often we use them in emergency medicine, including the recommended dosing, signs of toxicity, and treatment of toxicity.

Local anaesthetics fall into two divisions, based on their chemical structure:

  • the Esters (have one i): procaine, cocaine, tetracaine, chloroprocaine, etc
  • the Amides (have two i’s): lidocaine, bupivacaine, mepivacaine, prilocaine, ropivacaine, etc

Effect

These drugs have their effect as sodium-channel blocking medications with variable durations of action. Interestingly, 1% diphenhydramine has also been used as a local anaesthetic since the 1930s, given its sodium channel blocking mechanism. Local anaesthetics can be administered with other drugs, namely epinephrine, to help increase the duration of action and minimize the spread of the anaesthetic from the site of injection.

Maximum Dose

The safe maximal dose for the local anaesthetics is based on patient weight and correlates to the risk of systemic toxicity. The maximally safe dose of two common local anaesthetics is detailed below, and as you can see, the use of epinephrine allows for an increased dose of local anaesthetic injection.

Max dose without Epi Max dose with Epi Duration of Action
Lidocaine
4.5 mg/kg
7 mg/kg
0.5 - 1.5 hours
Bupivacaine
3 mg/kg
3 mg/kg
6-8 hours

Usage abd Absorbtion

Absorption into the bloodstream of a local anaesthetic can occur when the drug is injected directly into the bloodstream. Still, it can also occur in highly vascular areas or near neurovascular bundles in locations such as intracostal, epidural, and the brachial plexus. Local anaesthetic systemic toxicity (LAST) occurs when there are elevated circulating levels of local anaesthetic and occurs within minutes of injection. As you may know, lidocaine is used intravenously as an antiarrhythmic drug, and cocaine when used (or abused) systemically can cause numerous systemic effects and a sympathomimetic toxidrome. Bupivacaine is the most commonly discussed cause of LAST, and extra care should be taken when utilizing this for local anaesthesia.

Sign and Symptoms of LAST

Signs and symptoms of LAST predominate in the central nervous system and the cardiovascular system. CNS symptoms can include oral/perioral numbness, paresthesia, restlessness, tinnitus, fasciculations/tremors, seizures, decreased level of consciousness, and/or apnea. Cardiovascular symptoms can include: hypertension and tachycardia though more commonly vasodilation and hypotension, sinus bradycardia, AV blocs, conduction defects (notably: long PR and QRS), ventricular dysrhythmias, cardiovascular collapse, and/or cardiac arrest.

The differential diagnosis for LAST includes anaphylaxis (rare with amides), other sodium channel blockers (antihistamines, TCAs, cocaine, antimalarials), and anxiety. However, the timing nearly immediately following local anaesthetic administration should help one to hone in on the diagnosis.

Management

If a patient develops LAST, ACLS protocols should be followed. Furthermore, lipid emulsion (Intralipid) is the treatment that will help bind the anaesthetic in the bloodstream. While this medication is not on the WHO essential medication list, in a patient with LAST, Intralipid should be administered if available. Dosing is a 1.5 mL/kg bolus (standard dose of 100mL for 70kg patient), followed by a 0.25-0.5 mL/kg/min infusion until the patient is hemodynamically stable (and for at least 10 minutes).

How To Decrease Risk of LAST

A few strategies to minimizing the risk of causing harm to your patients when using local anaesthetics: 
 
  • know the maximum dose your patient can receive
  • know the dose you’re giving by dose (milligrams) and how that correlates to drug volume (mg/mL)
  • aspirate prior to injection(s) to ensure you are not in a blood vessel
  • consider using point of care ultrasound to ensure needle location

References and Further Reading

Cite this article as: J. Austin Lee, USA, "Local Anaesthetic Toxicity (LAST)," in International Emergency Medicine Education Project, November 23, 2020, https://iem-student.org/2020/11/23/local-anaesthetic-toxicity/, date accessed: November 25, 2020

More Posts By Dr. Lee

Giant Hogweed Burns

Giant Hogweed…and the Lesions it Causes.

Summer is the time when outdoor work and leisure activities increase. It is also the season when plants like giant hogweed grow and bloom most. Direct contact with this beautiful umbrella plant, however, leads to serious skin lesions and skin burns[1] that often necessitates a visit to the emergency room.

Have you ever heard of the giant hogweed?

The giant hogweed is an extremely toxic exotic plant particularly present in the British popular culture. It is also mentioned in the 1971 studio album entitled “Nursery Cryme” by the English rock band Genesis where the eternal struggle between this exotic plant and the English authorities trying to eradicate it is (humorously) narrated. Historically this plant was rediscovered in 1895 by two Italian doctors: Emile Levier and Carlo Pietro Stefano Sommier, to which they gave the botanical name of Heracleum mantegazzanium, in honour of their friend and physician Paolo Mantegazza, the first popularizer of Darwin’s scientific theories in Italy.

How can you recognize giant hogweed?

Giant hogweed, also known as Heracleum mantegazzianum, is considered to be the largest and most beautiful umbrella plant in the world[2]; it can reach a height of over 3 meters[3]. It is recognizable due to the colour of its leaves, which are a bright light green colour tending towards yellow with deep lobes and segmentations. The trunk is very thick and robust, similar to that of artichoke, with dark red streaks and surrounded by spiky hairs. The diameter of the umbrella makes it the largest among the umbrella plants. 

The fruits have an ovoid appearance, and at the moment of flowering, their envelopes remain attached to the base of the umbrella and subsequently tend to wither. Giant hogweed blooms from early spring until late summer, especially in the vicinity of wetlands (streams or canal banks). These characteristics differentiate it from the garden angelica (Angelica archangelica) and the common hogweed (Heracleum sphondylium).

Who is most at risk of coming across giant hogweed?

Gardeners, trekkers, forest workers, and people who work outdoors in wooded or undergrowth areas where giant hogweed is present are most at risk of injury caused by giant hogweed.

How is giant hogweed sap toxic?

The sap of giant hogweed contains different photoactive agents called furocoumarins, of which the most predominant is 5-MOP (5-methoxypsoralen). Injuries are caused when these photoactive agents are exposed to and activated by UV-A rays present in sunlight. This gives rise to a toxic process in which the furan ring of the photoactive agent is cross-linked with the pyrimidine bases of DNA in the patient’s skin, thus causing an increase in oxidative stress leading to cell membrane damage and subsequent inflammation and oedema. The culmination of these processes leads to the development of phytophotodermatitis (PPD)[4].

Similar to other plants capable of phototoxicity, skin damage is dependent on certain factors[5] such as:

  • The concentration of the phototoxic agent
    • During summer months, levels of phototoxic agents are higher. Moreover, they are more concentrated in fruit, present in intermediate levels in the leaves, and are minimally present in the stem.
  • The thickness of the skin
    • Damage is more extensive and deeper in the skin that is thinner.
  • Sun exposure
    • When sun exposure is prolonged, there is greater photoactivation and therefore greater damage.
  • Skin moisture
    • Sweat or dew that may be present on the skin can accelerate the toxicity process.

What are its symptoms?

Symptoms of giant hogweed exposure usually involve an erythematous lesion[6] accompanied by extremely intense pain. If not treated early, erythematous lesions evolve into burns[7] with the appearance of one or more liquid-filled vesicles. Generally, patients may have fatigue and slight tachycardia, but vital signs and laboratory test may be normal.

During the history and physical examination, staphylococcal infection, allergic dermatitis, purpura, impetigo, and fungal infection must be considered in the differential diagnosis.

Therapy

Upon contact, the subject should immediately wash the red area abundantly, dry it, and cover it to avoid sun exposure. Other recommendations would include avoiding to take baths and showers and apply high protection sunscreen to the lesion.

If erythema appears, the use of sulfadiazine cream and analgesic anti-inflammatory drugs should be considered. Moreover, the use of ice to reduce inflammation can also be useful. In the event of an injury characterized by one or more blisters or loss of tissue, a conservative treatment[8] consisting of cleansing with antiseptic solution (i.e. Clorexidine) and bandaging with synthetic microporous membranes[9] have proven effective. In cases where the phototoxicity process has been prolonged enough to cause extensive and deep burns, skin grafting and surgical debridement are necessary.

Take-home message

In conclusion, the message for our patients who operate or live in areas where giant hogweed is present is to “look but absolutely don’t touch” this beautiful plant. Secondarily, it is also important to subsequently report its presence to public authorities; in fact, many countries or regions follow a specific eradication program for this plant which can prove dangerous for humans and animals.

Look but absolutely don't touch this beautiful plant.

References and Further Reading

[1] https://www.plymouthherald.co.uk/news/plymouth-news/man-suffers-horror-burns-hogweed-4216136

[2] Heracleum mantegazzianum (giant hogweed) – Invasive Species Compendium – https://www.cabi.org/isc/datasheet/26911

[3] Derraik JG. Heracleum mantegazzianum and Toxicodendron succedaneum: plants of human health significance in New Zea-land and the National Pest Plant Accord. N Z Med J 2007;120: U2657.

[4] Marcos LA, Kahler R. Phytophotodermatitis. Int J Infect Dis 2015;9(July (38)):7–8.

[5] Pira E, Romano C, Sulotto F, et al. Heracleum mantegazzianum growth phases and furocoumarin content. Contact Derm 1989; 21:300e3.

[6] J Emerg Nurs. 2006 Jun;32(3):246-8. A 43-year-old woman with painful, vesicular lesions from giant hogweed photodermatitis. Langley DM(1), Criddle LM.

[7] Baker BG, Bedford J, Kanitkar S. Keeping pace with the media; Giant Hogweed burns – A case series and comprehensive review. Burns. 2017 Aug;43(5):933-938. DOI: 10.1016/j.burns.2016.10.018.

[8] Chan JC, Sullivan PJ, O’Sullivan MJ, Eadie PA. Full thickness burn caused by exposure to giant hogweed: delayed presentation, histological features and surgical management. J Plast Reconstr Aesthet Surg. 2011;64(1):128-130. doi:10.1016/j.bjps.2010.03.030

[9] Pfurtscheller K, Trop M. Phototoxic plant burns: report of a case and review of topical wound treatment in children. Pediatr Dermatol 2014;31:e156–9.

Cite this article as: Francesco Adami, Italy, "Giant Hogweed Burns," in International Emergency Medicine Education Project, August 31, 2020, https://iem-student.org/2020/08/31/giant-hogweed-burns/, date accessed: November 25, 2020

Question Of The Day #9

question of the day
qod9

Which of the following is the most appropriate next step in management for this patient’s condition?

This patient is suffering from sympathomimetic toxicity. Signs of a sympathomimetic toxidrome include agitation, psychosis, delirium, tachycardia, hypertension, diaphoresis, mydriatic (dilated) pupils, and decreased bowel sounds. The features of anticholinergic toxidromes overlap with many features of sympathomimetic toxidromes. A clinical finding that can be used to differentiate the two toxidromes is diaphoresis. Diaphoretic skin supports a sympathomimetic ingestion, while dry, warm skin supports anticholinergic ingestion. Examples of substances that can cause a sympathomimetic toxidrome ae cocaine, amphetamines, synthetic cannabinoids, ketamine, bath salts, and ecstasy (MDMA). The treatment for this toxidrome is mostly supportive care, such as benzodiazepines and cooling. Cocaine can cause coronary artery vasospasm along with sodium-channel blockade, which can predispose to cardiac arrhythmia. For this reason, a 12-lead EKG is important in any patient with possible cocaine toxicity. Sodium bicarbonate (Choice A) would be beneficial in salicylate toxicity, tricyclic antidepressant toxicity, or cocaine toxicity if the QRS was widened. The EKG for this patient has a normal QRS interval (<120msec). Physostigmine (Choice C) is an acetylcholinesterase inhibitor. This medication would likely worsen the patient’s tachycardia. Physostigmine is the antidote for anticholinergic toxicity. However, physostigmine should not be used in TCA overdose as it may increase the risk of cardiac arrhythmia. Naloxone (Choice D) is the antidote for opioid toxicity. Signs of opioid overdose include miotic (constricted) pupils, respiratory depression, and CNS depression. This patient does not possess these symptoms on exam. Diazepam (Choice B) is the best treatment. Correct Answer: B

References

Greene S. General Management of Poisoned Patients. “Chapter 176: General Management of Poisoned Patients”. In: Tintinalli JE, Ma O, Yealy DM, Meckler GD, Stapczynski J, Cline DM, Thomas SH. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th ed. McGraw-Hill.

Donaldson, R. (2019). Cocaine toxicity. WikEm. https://www.wikem.org/wiki/Cocaine_toxicity

Cite this article as: Joseph Ciano, USA, "Question Of The Day #9," in International Emergency Medicine Education Project, August 21, 2020, https://iem-student.org/2020/08/21/question-of-the-day-9/, date accessed: November 25, 2020

Question Of The Day #8

question of the day
qod 8 toxicology

Which of the following is the most likely cause of this patient’s condition?

This patient is suffering from an anticholinergic toxidrome. Symptoms of anticholinergic medication toxicity include altered mental status with agitation or delirium, tachycardia, hypertension, hyperthermia, mydriatic (dilated) pupils, hot and dry skin, decreased bowel sounds, and urinary retention. The sympathomimetic toxidrome is very similar to the anticholinergic toxidrome; however, patients with anticholinergic ingestions have dry skin while patients with sympathomimetic ingestions have diaphoretic skin. Some notable types of anticholinergics are atropine, antihistamines, Tricyclic antidepressants (TCAs), and Jimson weed. Amitriptyline (Choice A) is a TCA medication and can cause anticholinergic toxicity. When taken in high doses, a major adverse effect of TCAs is Na-channel blockade, resulting in QRS widening on EKG and cardiac arrhythmias. Therapy includes sodium bicarbonate and supportive care. This patient has a normal QRS interval on EKG, making this choice less likely. Cocaine (Choice B) is a sympathomimetic. Many features of the exam support sympathomimetic toxicity, but the presence of dry skin makes this choice less likely. Physostigmine (Choice C) is an acetylcholinesterase inhibitor which would have a cholinergic toxidrome if taken in excess. Features of this include bradycardia, bronchorrhea, bronchospasm, diarrhea, hypersalivation, sweating, and hyperactive bowel sounds. Treatment for cholinergic toxicity is atropine. Along with supportive care, physostigmine is the main treatment for anticholinergic toxicity. One exception is in TCA toxicity where physostigmine should be avoided. Diphenhydramine (Choice D) is an antihistamine with anticholinergic properties, and it is the most likely medication ingested in this case scenario. Correct Answer: D 

References

Greene S. General Management of Poisoned Patients. “Chapter 176: General Management of Poisoned Patients”. In: Tintinalli JE, Ma O, Yealy DM, Meckler GD, Stapczynski J, Cline DM, Thomas SH. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 9th ed. McGraw-Hill.

Cite this article as: Joseph Ciano, USA, "Question Of The Day #8," in International Emergency Medicine Education Project, August 14, 2020, https://iem-student.org/2020/08/14/question-of-the-day-8/, date accessed: November 25, 2020

Can I Eat This? – A Helpful Guide To Plant Toxicology – Cardiac Glycosides

CARDIAC GLYCOSIDES

Not only is the identification of toxic plants from their gross appearance a commonly tested topic in Emergency Medicine Board Exams, but it is also a necessary skill for doctors operating in institutions where an established Toxicology division does not exist or where the opinion of a specialist in the field is not immediately available.

This is the second part in a series of blog posts dedicated to providing you with original mnemonics and visual aids that serve to highlight a few classes of common toxic plants prominent for both their inclusion in the academic assessment as well as their prevalence in the community. These memory tools will attempt to highlight key features in the identification of well-known toxic plant species and are designed to aid clinicians from various regions of the globe as well as hone the skills of aspiring toxicologists.

Picture the Scene

A 21-year-old female is brought to your Emergency Department via ambulance due to persistent vomiting, abdominal pain, and some dizziness. She is visibly distressed, clutching her stomach, and reports having vomited at least six times over the past 3 hours. Her brother reports that she had been feeling ill with reported abdominal cramping and diarrhea for the past two days. Earlier that day, she had been given some herbal soup to help with her abdominal cramps by her grandmother, who had prepared it using leaves and flowers from the backyard garden. Soon after drinking the soup, the patient was reported to have multiple episodes of vomiting and began to experience some occasional dizziness, prompting contact of Emergency Medical Services and transfer to the hospital.

Upon initial examination, the patient’s vital signs were significant for a heart rate of 50 beats/minute with a Blood Pressure of 135/76 and spO2 of 95% on room air. No fever, abnormal breathing patterns, or signs of poor perfusion were noted. An Electrocardiogram (ECG) was done and revealed bradycardia, with a first-degree AV block, but no other T wave, QT, ST, or QRS segment abnormalities.

A laboratory workup was initiated, and the patient was given IV Atropine for her bradycardia. A Venous Blood Gas (VBG) was remarkable for hyperkalemia of 6.8 mEq/L with no acid/base disturbance. Therefore, treatment for hyperkalemia was initiated with IV Dextrose and Insulin as per standard management. When bradycardia persisted, a second dose of IV Atropine was given. The patient’s heart rate improved, but the blood pressure was noted to drop down to 95/68. After that, IV fluids were initiated, and the possibility of toxic ingestion explored by asking the patient’s brother for details of the ingredients present in the herbal soup.

The brother contacted the family at home and provided a picture of the plant used, as shown in Figure 1. The in-house Medical Toxicologist was shown the image and confirmed that the patient was suffering from Cardiac Glycoside toxicity secondary to the ingestion of an Oleander plant species.

Figure 1- Photograph of the flower used to make herbal soup. The flower was correctly identified as part of the toxic Oleander species.

Overview of Cardiac Glycoside Toxicity

Cardiac glycosides and related cardenolides represent a group of compounds that exhibit their effects primarily through their action on the Sodium-Potassium (Na+/K+) ATPase pump in cardiac myocytes and other tissues.[1] Inhibition of this pump, as outlined in Figure 2, causes an increase in intracellular Sodium (Na+), with subsequent activation of the Sodium-Calcium (Na+/Ca2+) exchanger, resulting in accumulation of intracellular calcium (Ca2+).

The increased intracellular Ca2+, along with direct stimulation of vagal tone, produces inotropic effects on the heart, increases ventricular ectopy, causes bradycardia, and impaired conduction through the atrioventricular (AV) node. At the same time, the inhibition of the Na+/K+ ATPase pump can lead to hyperkalemia.[2]

Cardiac glycosides are found in a variety of naturally occurring plant and animal species. Acute poisoning often presents with gastrointestinal manifestations (such as nausea, vomiting, abdominal pain or diarrhea), generalized body weakness, and dizziness. However, toxicity can also cause hyperkalemia and cardiotoxicity, represented by bradycardia, heart blocks, and various other dysrhythmias. Death is usually a result of ventricular fibrillation or tachycardia.[3]

Management involves addressing specific symptoms of severe disease. Atropine can be used to increase heart rate and reverse the effects on vagal tone in patients presenting with bradycardia. Reversal of toxicity can be achieved using Anti‐digoxin Fab as with Digoxin overdoses. Hyperkalemia can be managed using a combination of Insulin and dextrose solution to shift potassium back into cells. Activated charcoal may be used for initial decontamination, with Multidose activated charcoal for enhanced elimination.[4]

IV Calcium Chloride or Carbonate use in hyperkalemia was traditionally discouraged in patients suffering from cardiac glycoside poisoning. This was due to concerns that the additional calcium load would result in sustained cardiac contraction, termed as ‘the stone heart.’ However, several studies have since proven that such a phenomenon is unlikely to manifest in patients treated with IV Calcium.[5]

calcium mechanism

Figure 2- Mechanism of action of cardiac glycosides/digitalis drugs

Identifying Plants with Cardiac Glycoside toxicity

The most prominent species of plants known to contain cardiac glycosides include the foxglove plants Digitalis purpurea and Digitalis lanata, Oleander species (e.g., Nerium oleander and Thevetia peruviana), and Lily of the Valley (Convallaria majalis).[6] These plant species are commonly found in numerous tropical and subtropical countries around the world. Unfortunately, toxicity from accidental or intentional ingestion of their toxic leaves, roots, stems, and seeds is not uncommon and has, in several cases, lead to fatal outcomes for patients.[7-11]

cardiac glycosides plant identification

References and Further Reading

  1. Lingrel J. B. (2010). The physiological significance of the cardiotonic steroid/ouabain-binding site of the Na,K-ATPase. Annual review of physiology, 72, 395–412. https://doi.org/10.1146/annurev-physiol-021909-135725
  2. Benowitz, N. (2012). ‘Chapter 61- Digoxin and Other Cardiac Glycosides’ Poisoning & drug overdose. New York, N.Y.: McGraw Hill Medical.
  3. Kanji, S., & MacLean, R. D. (2012). Cardiac glycoside toxicity: more than 200 years and counting. Critical care clinics, 28(4), 527–535. https://doi.org/10.1016/j.ccc.2012.07.005
  4. Roberts, D. M., Gallapatthy, G., Dunuwille, A., & Chan, B. S. (2016). Pharmacological treatment of cardiac glycoside poisoning. British journal of clinical pharmacology, 81(3), 488–495. https://doi.org/10.1111/bcp.12814
  5. Levine, M., Nikkanen, H., & Pallin, D. J. (2011). The effects of intravenous calcium in patients with digoxin toxicity. The Journal of emergency medicine, 40(1), 41–46. https://doi.org/10.1016/j.jemermed.2008.09.027
  6. Hollman A. (1985). Plants and cardiac glycosides. British heart journal, 54(3), 258–261. https://doi.org/10.1136/hrt.54.3.258
  7. Bavunoğlu, I., Balta, M., & Türkmen, Z. (2016). Oleander Poisoning as an Example of Self-Medication Attempt. Balkan medical journal, 33(5), 559–562. https://doi.org/10.5152/balkanmedj.2016.150307
  8. S, Lokesh & Arunkumar.R,. (2013). A clinical study of 30 cases of Acute Yellow Oleander Poisoning. Journal of Current Trends in Clinical Medicine and Laboratory Biochemistry. 1. 29-31.
  9. Haynes, B. E., Bessen, H. A., & Wightman, W. D. (1985). Oleander tea: herbal draught of death. Annals of emergency medicine, 14(4), 350–353. https://doi.org/10.1016/s0196-0644(85)80103-7
  10. Janssen, R. M., Berg, M., & Ovakim, D. H. (2016). Two cases of cardiac glycoside poisoning from accidental foxglove ingestion. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne, 188(10), 747–750. https://doi.org/10.1503/cmaj.150676
  11. McVann, A., Havlik, I., Joubert, P. H., & Monteagudo, F. S. (1992). Cardiac glycoside poisoning involved in deaths from traditional medicines. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 81(3), 139–141.
Cite this article as: Mohammad Anzal Rehman, UAE, "Can I Eat This? – A Helpful Guide To Plant Toxicology – Cardiac Glycosides," in International Emergency Medicine Education Project, July 17, 2020, https://iem-student.org/2020/07/17/cardiac-glycosides/, date accessed: November 25, 2020

The Little-Known Dark Side of the Cannabis

the little known dark side of the cannabis

Bradycardia and Cannabinoid Hyperemesis Syndrome (CHS): two clinical pictures that are increasingly seen in the Emergency Department.

What are cannabinoids?

Cannabinoids are a series of extremely liposoluble chemical substances present in the Cannabis sativa plant. The most pharmacologically active among them is the delta-9-tetrahydrocannabinol (Δ9-THC). The prolonged or intense use of high doses of cannabis[1] could lead to acute cannabinoid intoxication causing bradycardia and cannabinoid hyperemesis syndrome (CHS).

Illustration of the Cannabis Sativa plant contained in the botanical atlas entitled "Köhler's medicinal plants" by the German botanist Hermann Adolph Köhler.
By Franz Eugen Köhler, Köhler's Medizinal-Pflanzen - List of Koehler Images

What do cannabinoids do in our body?

Cannabinoids are chemical substances that interact with two types of receptors present in the human body:

CB1 is a class of receptors distributed mainly in the central nervous system, but it is also found in the peripheral nervous system, the lungs, heart, and liver. The activation of this class of receptor at the central level causes a release of dopamine from the brain producing euphoria, analgesia, perceptual alteration, reduction of memory, and motor control. At the peripheral level, it inhibits the response of the sympathetic system, causing vasodilation and tachycardia.

CB2 is a class of receptors present at the peripheral level, in particular in the cells of the lymphoid system. They are implicated in the reduction of the inflammatory response and the reduction of hyperalgesia.

Who uses cannabinoids?

In Europe and the United States, cannabinoids are recreational drugs. Young people between 18 and 25 are main users[2]. In addition, cannabioids are used for medical-therapeutic purposes. For instance, in treating vomiting and nausea caused by chemotherapy, to stimulate appetite in AIDS patients, to treat chronic pain and muscle stiffness caused by multiple sclerosis, and in the treatment of depression.

What are the symptoms?

The common belief is that the intake of even large quantities of cannabinoids is harmless. However, subjects with acute cannabinoid intoxication are present more and more frequently in emergency departments (EDs) or clinics. They present a vast array of symptoms, including nausea, cyclical vomiting, agitation, short-term memory loss, cognitive deficits, psychosis, seizures, and arrhythmias. In addition, symptoms associated with the sympathetic system activation, such as mydriasis, hypertension, and tachycardia, are often described.

In the ED, what should we pay attention to?

There are two particularly relevant clinical pictures related to acute cannabinoid poisoning: CHS and bradycardia.

What is cannabinoid bradycardia?

The effects of cannabinoids on the heart depend on their dosage. At a low to moderate dose, there is tachycardia and arterial hypertension (through an increase in the activity of the sympathetic nervous system); at a high dose, there is sinus bradycardia, hypotension, and decreased myocardial contractility[3],[4]. The beginning of the arrhythmic effect peaks at 30 minutes from the intake and can last several hours. In the literature, the arrhythmic effects are described together with cases of sinus tachycardia, sinus bradycardia, atrioventricular blockages, and cardiac arrest.

What is CHS?

CHS is characterized by episodes of prolonged cyclic vomiting, with an average duration of 24–48 h, accompanied by abdominal pain separated by extended periods (even months) of an absence of symptoms. These episodes of vomiting are incredibly resistant to conventional therapy using drugs, such as metoclopramide, ondansetron, or promethazine. In addition, the acute phases can be so severe as to be responsible for dehydration, water, and electrolyte disturbances and disorientation.

How do we diagnose CHS?

The diagnosis of CHS is clinical and can potentially be represented by the triad:

  • Marijuana use over a prolonged period;
  • Intractable vomiting that can last for hours or days and does not respond to the common anti-emetic therapy; and
  • Improvement of symptoms after a hot shower or hot bath or use of topical capsaicin.

However, this syndrome enters into differential diagnosis with psychogenic vomiting, cyclic vomiting syndrome [5], and hyperemesis gravidarum [6],[7].

How do we treat CHS?

First of all, resuscitation through the administration of fluids and electrolytic rebalancing are priorities. After that, CHS seems to resolve a few minutes after a hot shower or bath [8] or the use of topical Capsaicin cream applied in a thin layer at the abdominal, thoracic, or lumbar level[9]. However, the reasons for such therapy are not yet clear. In addition, Haloperidol[10] and the use of Beta-blockers[11] were also found to be effective in the treatment of CHS. After medical treatment, it is important to educate the patient about cannabinoid hyperemesis and to inform how the cessation of cannabinoid use can resolve this clinical picture.

What is the take-home message?

The liberalization of the laws on the use of cannabinoids and a growing favorable public opinion about them will likely increase acute cannabinoid intoxication cases in the EDs. In conclusion, a better knowledge of these two clinical pictures among emergency clinicians could avoid costly and time-consuming tests, scans, and procedures in these patients.

Cite this article as: Francesco Adami, Italy, "The Little-Known Dark Side of the Cannabis," in International Emergency Medicine Education Project, April 17, 2020, https://iem-student.org/2020/04/17/dark-side-of-the-cannabis/, date accessed: November 25, 2020

References

  1. Smart R, Caulkins JP, Kilmer B, Davenport S, Midgette G. Variation in cannabis potency and prices in a newly legal market: evidence from 30 million cannabis sales in Washington state. Addiction. 2017 Dec;112(12):2167–77.
  2. National Institute on Drug Abuse. Nationwide Trends. 2015; https://www.drugabuse. gov/publications/drugfacts/nationwide- trends. Accessed May 26, 2018.
  3. Pacher, P., Steffens, S., Haskó, G. et al. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol 15151–166 (2018) doi:10.1038/nrcardio.2017.130
  4. David O. Andonian, Shauna R. Seaman, Elaine B. Josephson, Profound hypotension and bradycardia in the setting of synthetic cannabinoid intoxication – A case series The American Journal of Emergency Medicine, Volume 35, Issue 6, June 2017, Pages 940.e5-940.e6
  5. Bhandari S, Jha P, Thakur A, Kar A, Gerdes H, Venkatesan T. Cyclic vomiting syndrome: epidemiology, diagnosis, and treatment. Clin Auton Res. 2018 Apr;28(2):203–9.
  6. Alaniz VI, Liss J, Metz TD, Stickrath E. Cannabinoid hyperemesis syndrome: a cause of refractory nausea and vomiting in pregnancy. Obstet Gynecol. 2015 Jun;125(6):1484–6
  7. Volkow ND, Compton WM, Wargo EM. The Risks of Marijuana Use During Pregnancy. JAMA. 2017 Jan;317(2):129–30
  8. Lapoint J, Meyer S, Yu CK, Koenig KL, Lev R, Thihalolipavan S, et al. Cannabinoid Hyperemesis Syndrome: Public Health Impli- cations and a Novel Model Treatment Guideline. West J Emerg Med. 2018 Mar; 19(2):380–6.
  9. Graham J, Barberio M, Wang GS. Capsaicin Cream for Treatment of Cannabinoid Hyperemesis Syndrome in Adolescents: A Case Series. Pediatrics. 2017 Dec;140(6):e20163795.
  10. Hickey JL, Witsil JC, Mycyk MB. Haloperidol for treatment of cannabinoid hyperemesis syndrome. Am J Emerg Med. 2013 Jun; 31(6): 1003.e5–6.
  11. Richards JR, Dutczak O. Propranolol Treatment of Cannabinoid Hyperemesis Syn- drome: A Case Report. J Clin Psychopharmacol. 2017 Aug;37(4):482–4.

Can I Eat This? – A Helpful Guide To Plant Toxicology – Anticholinergics

A Helpful Guide To Plant Toxicology – Anticholinergics

Introduction

Not only is the identification of toxic plants from their gross appearance a commonly tested topic in Emergency Medicine Board Exams, but it is also a necessary skill for doctors operating in institutions where an established Toxicology division does not exist or where the opinion of a specialist in the field is not immediately available.

Various mnemonics and visual aids serve to highlight a few classes of common toxic plants that are prominent for both their inclusion in the academic assessment as well as their prevalence in the community. This series will sequentially present a series of visual aids and mnemonics that highlight key features in the identification of well-known toxic plant species, designed to aid clinicians from various regions of the globe as well as hone the skills of aspiring toxicologists.

Picture the Scene

A 28-year-old male is brought to your Emergency Department (ED) via ambulance due to a reportedly altered mental status. His wife, who accompanied the paramedics, states that she found him lying unconscious in the grass near a basket he was using to collect berries during an outdoor picnic in the fields. He was arousable at the scene but has had a fluctuating level of consciousness up to arrival to the hospital.

Upon initial examination, the patient is observed to be irritable with irregular, shallow breathing. Vital signs revealed a Blood Pressure of 127/75 mmHg, Heart Rate of 140, Respiratory rate of 24, Temperature of 37.9 C, and spO2 96% on room air. His pupils were found to be equally reactive to light but were significantly dilated, and his mucus membranes were notably dry.

The patient’s wife, believing the cause for her husband’s condition to be ingestion of the berries from the field, approaches you and shows you pictures of the plants she had photographed near where her husband was found. (see below images)

anticholinergic
anticholinergic

Why we care about toxic plant identification

The intoxicated patient, while frequently encountered in the ED, poses a uniquely challenging puzzle for the average ED Physician. Beyond the routine resuscitative and supportive care, the doctor who receives a patient that has consumed an unknown substance is tasked with the burden of deducing what kind of substance was taken and the expected sequelae for the same.

Among the numerous causes of intoxication, ingested plant species are a particularly ambiguous class of toxic substances to identify because the vast majority of intoxicated patients consume them unknowingly with only vague descriptions for what they ate. Often, however, these plants are brought with the patient or are present on their person at the time of arrival.

Whereas a vast majority of cases that present to the Emergency Department may not exhibit similar tell-tale signs and symptoms, the patient in the case described above displayed clinical manifestations typical to an anticholinergic syndrome. Furthermore, the photographs provided by the patient’s wife confirmed the cause of his symptoms as toxic ingestion of berries from the plant species Atropa Belladonna.

Plants with anticholinergic toxicity

The two most important plant species that contribute to this class of toxicity are the Datura stramonium (Jimson weed, angel’s trumpet), and the Atropa Belladonna (Deadly nightshade). The seeds of D. Stramonium and the berry-like fruits and leaves of A. Belladonna contain scopolamine, hyoscyamine and atropine. Ingestion of these parts of the plant results in suppression of Acetylcholine in the body, manifesting as an antimuscarinic syndrome that is characterized by dry skin, altered mental status, flushing, decreased gastrointestinal motility, increased body temperature, tachycardia, pupillary dilation (mydriasis) and urinary retention.

The above constellation of symptoms is usually simplified by using the following phrases:

‘Mad as a Hatter’ – Delirium/Altered Mental Status
‘Hot as a Hare’ – Hyperthermia
‘Red as a Beet’ – Flushing
‘Bloated as a Toad’ – Decreased gut motility/Constipation
‘Blind as a Bat’ – Mydriatic pupils
‘Dry as a Bone’ – Dry skin/decreased sweat production

Management involves benzodiazepines for agitation, adequate hydration, and supportive care. Physostigmine is reserved for cases refractory to Benzodiazepines.

Plant Identification

A useful method of visual identification of the plant species outline above is as follows:

Black in green, Black on green Don’t trust their high, they inhibit Acetylcholine!

jimson weed - Datura Stromonium
Jimson Weed - Datura Stromonium
Atropa Belladonna
Deadly nightshade - Atropa Belladonna
jimson weed - Datura Stromonium
Jimson Weed - Datura Stromonium
Atropa Belladonna
Deadly nightshade - Atropa Belladonna

Mnemonic break-down

  • Black in green

    Black-colored toxic seeds reside within green ‘spiky’ fruit of Datura stramonium (Jimson weed)

  • Black on green

    Black-colored berry-like fruit (often mistaken for common blueberries) nestled on top of greenish petal-like structures and leaves of Atropa Belladonna (Deadly nightshade)

  • Don’t trust their high

    These plant species are commonly ingested for recreational purposes due to reported hallucinogenic properties

  • They inhibit Acetylcholine

    Both cause antimuscarinic syndrome: Dry skin, flushing, decreased GI motility, hallucinations, mydriasis, hyperthermia, tachycardia, urinary retention

Cite this article as: Mohammad Anzal Rehman, UAE, "Can I Eat This? – A Helpful Guide To Plant Toxicology – Anticholinergics," in International Emergency Medicine Education Project, April 6, 2020, https://iem-student.org/2020/04/06/anticholinergics/, date accessed: November 25, 2020

Reference

  • Lim, C.S., Aks, S.E. (2017), ‘Chapter 158 – Plants, Mushrooms and Herbal Medications’, Rosen’s emergency medicine 9th edition, Pg. 1957 – 1973

Learning from The Past

Toxicological Intimations from The Life and Works of Vincent Van Gogh

While his art is now highly renowned and eulogized, Vincent Willem Van Gogh spent his lifetime in considerable obscurity, fraught with numerous unprofitable endeavors, misfortunes and various illnesses leading up to his ultimate suicide at the age of 37. Years of extensive research into the possible ailments that plagued Van Gogh near the end of his life have revealed several factors that could have contributed to both his physical symptoms as well as the art style of his paintings.

van gogh
Vincent Willem Van Gogh - 1853-1890

Seizures

Much of Van Gogh’s neuropsychiatric symptoms, most notably his episodes of seizures, began around the time of his move to the city of Arles in southern France. While the pathology of his seizures has been most famously described by Henri Gastaut (1) as a form of temporal lobe epilepsy, the cause of his disorder remains uncertain. While it is reasonable to point to his poor diet and excessive alcohol consumption as the primary factor for his symptoms, a look into Van Gogh’s substance abuse indicates the possibility of several other causes for his convulsions.

  • Absinthe

    Dr. Hemphill (1961) was the first psychiatrist to link absinthe to Van Gogh’s illness (2). Absinthe is an alcoholic drink that became largely popular around the time of Van Gogh’s move to Paris. Traditionally, it comprises anise, fennel, wormwood and various herbs that undergo distillation. However, it is perhaps most popularly known for its supposed hallucinogenic properties, attributable to the chemical component Thujone. While the oil of wormwood is also known to have some convulsant properties (3), the majority of seizures that occur from consumption of absinthe are likely due to the toxic properties of Thujone. In the year 2000, it was revealed that Thujone possesses the ability to block the γ-aminobutyric acid type A (GABA A) receptor chloride channel (4). GABA works in the human body as a neurotransmitter that inhibits brain cell firing. Binding of GABA to its target receptor causes the influx of Chloride ions into cells, thereby producing inhibitory effects that most commonly cause sedation. Whereas anticonvulsant, sedative and anesthetic medication commonly stimulate the GABA receptor, Thujone antagonizes its effects, resulting in the increased excitation of brain cells that predisposes the body to seizures. Hemphill 1961 noted that, not only was Van Gogh’s consumption of absinthe excessive even by normal standards at the time, he was, in fact, more sensitive to its detrimental effects. To add further insult to injury, the continued use of absinthe during this time caused Van Gogh to develop pica. Pica, usually the consequence of a nutritional disorder, causes individuals to crave the consumption of items that are not considered a source of nutrition (e.g. stones, dirt, hair, paint, etc). The phenomenon usually occurs as a result of need-determined behavior secondary to malnutrition (5). Van Gogh’s pica involved a specific predilection toward consuming ‘turpene’ chemicals such as camphor and turpentine oils.

  • Camphor

    Wilfred Niels Arnold, a biochemist who analyzed the mental health and lifestyle of Vincent Van Gogh (6), connected several of Van Gogh’s odd habits to substance use. While he was hospitalized for having cut off his ear in 1888, the artist suffered from insomnia. In an effort to ameliorate his symptoms, reports suggest that he frequently placed camphor under his pillow to help him fall asleep. In addition to this, as described above, he also routinely ingested the substance as a consequence of his pica disorder. Although originally extracted from the barks of the Cinnamomum camphora tree, camphor is now produced only synthetically from components in turpentine and is found in non-prescription products such as lip balms, skin coolers (Vicks VapoRub) and various creams for muscle aches. During Van Gogh’s time, the substance was likely procured in an oil-based form that he both ingested and used topically. The mechanism of toxicity of camphor is unknown, but it has been associated with depression of the Central Nervous System, producing signs and symptoms such as confusion, hyperreflexia, headache, agitation and seizure. (7)

  • Turpentine

    With his increasing psychosis and advanced disease, Van Gogh’s odd consumption habits eventually extended to turpentine oils in the year 1889. Primarily attributed to his pica, Van Gogh was noted to drink the essence of turpentine as well as chew on his oil colors. Turpentine oils, produced by distilling the resin obtained from trees (mainly pine trees), are comprised of chemicals known as turpenes, most notably pinene. Inhalation of large quantities or ingestion of the compound has been shown to produce convulsions, gastric irritation, dizziness, agitation, cyanosis, coma and even death in patients. (8)

Vision Changes

Speculation exists surrounding the influence of drugs on Van Gogh’s vision. Though most authors now believe this to be a mostly unfounded connection, the predominant use of yellow (Figure 1) coupled with halo-like patterns (Figure 2) observed in some of Van Gogh’s later works have often been attributed to toxicity from digitalis.
Figure 1 – ‘Wheatfield With a Reaper’, 1889 - The abundance of yellow color in paintings such as this one has been said to have been associated with yellow vision seen with Digitalis toxicity
Figure 1 – ‘Wheatfield With a Reaper’, 1889 - The abundance of yellow color in paintings such as this one has been said to have been associated with yellow vision seen with Digitalis toxicity
Figure 2 – ‘The Starry Night’, 1889  - Turbulent flows and spirals used to represent stars have been linked to  ‘visual halos’ infamous in Digitalis toxicity
Figure 2 – ‘The Starry Night’, 1889  - Turbulent flows and spirals used to represent stars have been linked to  ‘visual halos’ infamous in Digitalis toxicity

While researchers believe there to be very little evidence of digitalis use in Van Gogh’s life, the association, at the very least, provides a useful mnemonic for medical students to familiarize themselves with the vision changes related to digitalis toxicity.

  • Digitalis

    Digitalis is a cardiac glycoside that primarily acts on the cardiac myocyte by inhibiting the Na+/K+ ATPase pump (outlined in Figure 3). Under normal conditions, this pump acts to exchange intracellular Na+ for K+. Therefore, blocking its activity results in an accumulation of intracellular Na+, which then allows the adjacent Na+/Ca2+ exchange channel to use the excess intracellular Na+ to bring in more Ca2+, resulting in a net increase in intracellular Ca2+ which acts as an inotrope for the cardiac cells.

Figure 3 – Mechanism of action of Digoxin/Digitalis on cardiac myocytes
Figure 3 – Mechanism of action of Digoxin/Digitalis on cardiac myocytes

Digitalis is said to purport its effects on vision through a similar mechanism. In this case, acting on Na+/K+ ATPase channels in the retina results in changes to the arrangement of rods and cones, thereby propagating the symptoms of ‘Xanthopsia’- a term used to describe a distortion in color perception with a tendency toward visualizing colored halos.

The presumption that Van Gogh was exposed to digitalis arose from the fact that, during those times, digitalis (extracted from the plant species, known commonly as the foxglove) may have been used to treat epilepsy. In fact, a plant resembling the foxglove was noted in Van Gogh’s portrait of his psychiatrist (Figure 4).

Figure 4 – Portrait of Dr. Gachet - Dr. Gachet, the psychiatrist, supposedly charged with the treatment of Van Gogh’s Epilepsy is seen painted here with a flower that intriguingly resembles the foxglove plant (from which Digitalis is derived)
Figure 4 – Portrait of Dr. Gachet - Dr. Gachet, the psychiatrist, supposedly charged with the treatment of Van Gogh’s Epilepsy is seen painted here with a flower that intriguingly resembles the foxglove plant (from which Digitalis is derived)

Worsening Mental State

Finally, great debate exists surrounding the cause for Van Gogh’s worsening mental state during the last years of his life. While everything from malnutrition to Acute Intermittent Porphyria has been implicated in the development of his cognitive decline, an interesting toxicological cause that may have been, at least in part, a culprit for his condition is lead poisoning.

  • Lead Poisoning

    The prevalence of lead-based paints in those times, coupled with Van Gogh’s peculiar consumption of oils and paint (pica), suggests both inhalation and ingestion as possible routes of lead exposure for Van Gogh. While exposure does not necessarily confirm poisoning in this case, some of Van Gogh’s evident neuropsychiatric decline does match the psychotic features associated with lead poisoning (also referred to as ‘Saturnism’). An outline of common manifestations of lead poisoning is mapped below (Figure 5)

Figure 5 - Features of lead poisoning
Figure 5 - Features of lead poisoning

Conclusion

Since most of the information obtained on Van Gogh’s illness is extracted from unreliable accounts and excerpts of letters he wrote toward the end of his life, any causal association, toxicological or otherwise, would ultimately be pure conjecture. At the very least, however, the relations outlined above provide an educational insight into the possibilities and mechanisms by which the substances prevalent in Van Gogh’s lifestyle could, in part, be contributory to his tendencies and even his psychiatric disease.

References and Further Reading

  1. Gastaut H: La maladie de Vincent van Gogh envisagée a la lumière des conceptions nouvelles sur l épilepsie psychomotrice. Ann Méd Psychol (Paris) 1956; 114:196–238
  2. Hemphill RE (1961): The illness of Vincent van Gogh. Proc Roy Soc Med 54: 1083–1088
  3. Simonetti G. Simon & Schuster’s Guide to Herbs and Spices. New York: Simon & Schuster; 1990. pp. 261–262
  4. Hold K M, Sirisoma S I, Ikeda T, Narahashi T, Casida J E. Proc Natl Acad Sci USA. Alpha-thujone (the active component of absinthe): gamma-aminobutyric acid type A receptor modulation and metabolic detoxification. 2000;97:3826–3831
  5. Richter CP. Self-selection of diets. Essays in Biology. Berkeley, CA: University of California Press; 1943
  6. Vincent van Gogh: chemicals, crises, and creativity, Author: Wilfred Niels Arnold, Published by Birkhäuser, 1992
  7. Phelan WJ, 3rd. Camphor poisoning: over-the-counter dangers. Pediatrics 1976; 57:428–431, Klingensmith WR. Poisoning by camphor. J Am Med Assoc 1934; 102:2182–2183
  8. Pande TK, Pani S, Hiran S, Rao VVB, Shah H, Vishwanathan KA (1994) Turpentine poisoning: a case report. Forensic Sci Int 65: 47–49
Cite this article as: Mohammad Anzal Rehman, UAE, "Learning from The Past," in International Emergency Medicine Education Project, August 7, 2019, https://iem-student.org/2019/08/07/learning-from-the-past/, date accessed: November 25, 2020

Toxicology Pearls – Active Charcoal – Infographic

toxicology pearls - active charcoal

Activated Charcoal Application

Emergency Indications

  • Oral intake < 60 minutes
  • the life-threatening dose of the toxic substance

Multi-Dose Activated Charcoal (MDAC) Indications

  • Life-Threatening Oral Intake of
    • Carbamazepine
    • Dapsone
    • Phenobarbital
    • Quinine
    • Theophylline

Contraindications

  • For patients with compromised airway reflexes, unless they are intubated. If the critical situation of the patient indicates intubation, then, gastric lavage may be performed. Intubation, only for decontamination, is not recommended.
  • Oral intake of caustic substances
  • Late presentation
  • Increased risk and severity of aspiration associated with AC use (e.g., hydrocarbon ingestion)
  • Need for endoscopy (e.g., significant caustic ingestion)
  • Toxins poorly adsorbed by AC (e.g., metals including iron and lithium, alkali, mineral acids, alcohols)
  • Presence of intestinal obstruction (absolute contraindication) or concern for decreased peristalsis (relative contraindication)

Equipment and Patient Preparation

There is no specific equipment for activated charcoal administration. However, drinking the charcoal can be very unpleasant for many patients, especially children. Therefore, mixing with fruit juice can be an option. In addition, if necessary nasogastric or orogastric tube placement can facilitate the active charcoal treatment.

Procedure steps

  • Recommended empirical single-dose of activated charcoal is as follows:
    • <1 year – 0.5-1 g/kg or 10-25 g
    • 1-12 years – 0.5-1 g/kg or 25-50 g
    • >12 years – 1-2 g/kg or 25-100 g
By James Heilman, MD [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)], from Wikimedia Commons
By James Heilman, MD [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)], from Wikimedia Commons
  • Multidose activated charcoal
    • Give the recurrent dose of charcoal by 0.5 g/kg (≤50 g) every 4 hours
  • How to administer:
    • If the patient is awake and cooperative, AC may be given orally. Alternatively, it may be given by gastric or nasogastric tube, if these procedures are indicated.
    • Mixing the activated charcoal with fruit juices increases tolerability.
    • If the patient is unconscious or airway is compromised, gastric lavage should be done, and activated charcoal should be given after intubation. Tracheal intubation is not recommended solely in order to give activated charcoal. Only activated charcoal is to be given, the nasogastric tube is adequate and is preferred.
    • If MDAC is indicated, the gastric tube should be withdrawn after gastric lavage and the first dose of activated charcoal. Further doses should be given via nasogastric tube.

Hints and Pitfalls

  • The substances that cannot bind to activated charcoal are as follows:
    • Lithium
    • Strong acids and bases
    • Metals and inorganic minerals
    • Alcohols
    • Hydrocarbons
  • Multi-dose activated charcoal enhances elimination of (But not necessarily indicated in all)
    • Amitriptyline
    • Aspirin
    • Caffeine
    • Carbamazepine
    • Cyclosporine
    • Dapsone
    • Digoxin
    • Disopyramide
    • Nadolol
    • Phenobarbital
    • Phenytoin
    • Piroxicam
    • Quinine
    • Sotalol
    • Sustained-release thallium
    • Theophylline
    • Valproate
    • Vancomycin
  • MDAC increase the risk of constipation and bowel obstruction in some cases. Therefore, consider adding a cathartic agent to the second or third dose of AC.

Post Procedure Care and Recommendations

  • Control possible nausea and vomiting.
  • Look for traces of aspiration or gastrointestinal complications.

Complications

Complications of AC and MDAC include:

  • Constipation, diarrhea, vomiting
  • Pulmonary aspiration

Pediatric, Geriatric, and Pregnant Patient Considerations

  • In pediatric and geriatric patients, extra caution should be exercised to avoid and monitor complications.
  • Activated charcoal is considered safe for pregnant women.

You may want to look these too...

Cite this article as: iEM Education Project Team, "Toxicology Pearls – Active Charcoal – Infographic," in International Emergency Medicine Education Project, July 29, 2019, https://iem-student.org/2019/07/29/toxicology-pearls-active-charcoal-infographic/, date accessed: November 25, 2020

A Farmer’s Dilemma

Farmer's Dilemma

Case Presentation

It was a rainy night preceding my morning shift as a year 3 EM resident at one of our training centers in Abu Dhabi. The paramedics barged in with an agitated patient, who was found soaking wet in a farm field.

According to brief history that we got from the paramedics, the patient works at a farm and his boss found him collapsed, cold to touch and confused in the early morning hours. Paramedics also reported a confused, hypothermic, and tachycardic patient. They brought him directly to the ED, with no accompanying friends or family.

As we proceeded to resuscitate the patient, we noted that his initial vital signs did confirm hypothermia of 32 Celsius measured rectally, tachycardia, hypertension, and normal O2 saturation. We hooked him to the monitor, removed his wet clothing, gained IV access, started him on warm IV fluids, and covered him with blankets and a warming Bair Hugger (a warming blanket system).

Physical Exam

The patient was confused, agitated and uttering incomprehensive words, with a GCS of 11 (E3 V3 M5). I proceeded to examine him looking for more clues of why he was laying semiconscious under the rain all night. Systematic physical examination revealed pinpoint pupils, frothing and excessive salivations. Furthermore, diffuse mild crackles were noted on chest auscultation, and he was tachycardic with a regular rate and rhythm. Remaining physical exam was unremarkable, and a complete neurological exam was challenging.

Differential Diagnosis and Workup

Thinking of a broad differential diagnosis of altered mental status, systematic consideration of all possible etiologies similar to our patient presentation was reviewed. We have considered metabolic derangements, head trauma, CNS causes such as seizures and post-ictal status, infectious causes such as pneumonia or meningitis, and toxicologic causes, such as alcohol withdrawal, or medications overdose.

You may find useful this mnemonic for altered mental status!

ALTERED MENTAL STATUS

Further management plan included giving him benzodiazepines for the agitation and possible post-ictal status. We collected basic blood work and proceeded for a head CT to rule out traumatic or atraumatic intracranial pathologies. Blood workup was inclusive of an alcohol level, Aspirin, Acetaminophen level, and a urine toxicology screen.

As the patient returned from the CT, he apparently had passed the copious amount of loose stools, that smelled surprisingly like garlic that studded the ED with its smell.

The head CT was normal, and most of his blood workup came back unremarkable. But, he remained confused and agitated as the benzodiazepines were wearing off and despite all the warming measures. ECG showed only sinus tachycardia, and a chest X-Ray was unremarkable.

smells like garlic!

What do you think? What are the causes for this?

agents smells like garlic

phosphorus, tellurium, inorganic arsenicals and arsine gas, organophosphates, selenium, thallium, dimethyl sulfoxide
Learn More

The garlic smell did give us a lead though, we thought further of possible toxic agents that may give such a smell, along with a consistent similar clinical picture.

Case Management and Disposition

Collecting our clues once more, we had pinpoint pupils, frothing, salivation, wet lungs, vomiting and loose motions. Patient’s collective symptoms and signs indicated a Cholinergic Toxidrome, possibly due to Organophosphates ingestion.

The patient was already decontaminated with removal of all his clothes. All healthcare providers were equipped with personal protective equipment.

This was confirmed an hour later when his farm owner showed up with a Pesticides Bottle that he found near him in the early morning hours before calling an ambulance. Pesticide is shown in Figure. The content of the bottle is consistent with Organophosphates Toxicity, and hence his Cholinergic Toxidrome.

Pesticide Bottle Found Next To The Patient.
Pesticide Bottle Found Next To The Patient.

He was started on Atropine, and Pralidoxime, assessed and admitted to the ICU with arranged psychiatric consult to assess his suicidal ideations once he stabilizes.

Critical Thinking and Take-home Tips

A collection of symptoms and physical signs caused by a certain toxic agent.

Cholinergic
Anticholinergic
Sedative/Hypnotic
Sympatholytic
Sympathomimetics

Cholinergic toxicity represents a cholinesterase inhibitor poisoning. It results from the accumulation of excessive levels of acetylcholine in synapses. Clinical picture resulting from the Acetylcholine build up depends on the type of receptors that it stimulates and where is it found in the body. It can stimulate the nicotinic and muscarinic receptors. The balance of these stimulations reflects such clinical presentations.

Think of the symptoms that can be caused depending on the type of receptors affected by the buildup of acetylcholine.

Muscarinic Receptors – SLUDGE(M)

  • Salivation
  • Lacrimation
  • Urination
  • Diarrhea
  • Gastrointestinal pain
  • Emesis
  • Miosis

Nicotinic Receptors (NMJ) – MTWThF

  • Mydriasis/Muscle cramps
  • Tachycardia
  • Weakness
  • Twitching
  • Hypertension
  • Hyperglycemia
  • Fasciculations

These are called the Killers B’s which consist of Bradycardia, Bronchorrhea and Bronchospasm.

Decontamination should always be considered first in all cases with possible hazardous exposure from the patient and his environment to all health care providers in contact with him. All caregivers should wear appropriate personal protective equipment’s and make sure to remove all clothing and possible objects with the suspected contaminant.

Supportive care is a cornerstone to all unstable patients, make sure that they are monitored, with proper IV access and supplemental oxygen as needed.

Furthermore, airway management is lifesaving in similar patients, as bronchorrhea is one of the killer B’s and can lead to high fatality.

Antidotes such as Atropine and Pralidoxime in Cholinergic toxicity are paramount, as they help reverse the etiology, and prevent further worsening of the toxicity.

Make sure that such patients are admitted under needed specialty care with proper observation and reassessment for the patient.

Consult a toxicologist if feasible in your center to provide you with further management details and interventions that can help your patients better.

Conclusion

Organophosphates can be found in pesticides, chemical weapons such as nerve gases, and few medications as well such as neostigmine or edrophonium. They are highly lipid soluble making them easily absorbed via breathing and skin contact as well. Encountering similar patients, it is quite important to always be systematic in your approach, resuscitate your patient first, and make sure to use your history taking as feasible and physical examination to collect all the clues needed to narrow down your differentials and find the most appropriate treatment needed for your patient.

References and Further Reading

  1. Organophosphate toxicity on WikEM: https://www.wikem.org/wiki/Organophosphate_toxicity
  2. Das RN, Parajuli S. Cypermethrin poisoning and anti-cholinergic medication- a case report. Internet J Med Update. 2006;1:42–4.
  3. Aggarwal, Praveen et al. “Suicidal poisoning with cypermethrin: A clinical dilemma in the emergency department.” Journal of emergencies, trauma, and shock vol. 8,2 (2015): 123-5. doi:10.4103/0974-2700.145424
  4. Lekei EE, Ngowi AV, London L. Farmers’ knowledge, practices and injuries associated with pesticide exposure in rural farming villages in Tanzania. BMC Public Health. 2014;14:389. Published 2014 Apr 23. doi:10.1186/1471-2458-14-389

Suggested Chapters and Posts in iEM

Cite this article as: Shaza Karrar, UAE, "A Farmer’s Dilemma," in International Emergency Medicine Education Project, July 19, 2019, https://iem-student.org/2019/07/19/a-farmers-dilemma/, date accessed: November 25, 2020

A Case Of Cyanide Poisoning From Vitamin B17

Since their advent in the 1930s, ‘vitamin pills’ have shown a steady rise in both variety and consumption patterns in patients. Guided by the promise of a healthier lifestyle and overall wellness, the use of vitamin supplements has become increasingly commonplace and you would be hard-pressed to find a patient who isn’t on some form of regular vitamin. Most of these nutritional adjuncts are either indicated for chronic conditions or, at the very least, harmless additions to daily regimens and do not usually warrant a second thought when described during patient encounters in the ED. However, not all supplements are as benign as they might seem. The following case report details the events that unfolded when a 45-year-old male patient accidentally ingested more tablets than were indicated for a vitamin he had purchased online.

Case Presentation

A 45-year-old male presented to the Emergency Department with complaints of fatigue, shortness of breath and anxiety following a possible over-ingestion of vitamin supplement tablets. As per the patient, he ordered a bottle of vitamin supplements online and admitted to misreading the instructions on the label. Instead of the recommended one tablet per day dose, he reported taking eight tablets for the first time earlier that morning. The tablets were bought without the need for prescription and, according to the patient’s research, were meant to be “good for promoting long life and preventing cancer.” Upon arrival to the ED, the patient was visibly anxious and mildly diaphoretic, stating that “I know I took too many tablets. Am I going to be okay?”

Physical Exam

Examination revealed a tired-looking patient with vital signs significant only for mild tachycardia of 105 and spO2 95% on room air. Otherwise, physical exam was normal. 

ABG

The initial ABG and preliminary lab tests revealed no significant findings, mildly elevated lactate of 1.8, for which the patient was placed on fluids with observation.

Being a particularly busy shift at the Emergency Department, the patient’s presentation coupled with his history of seemingly harmless vitamin ingestion, did not produce an immediate cause for concern. Nevertheless, he was monitored frequently until his investigations returned, during which time he remained clinically stable and without any subjective complaint besides a persistent feeling of fatigue.

A second ABG was performed and, despite the fluids, demonstrated a rise in his lactate levels to 2.6. By this time, the patient’s companion had made their way to the hospital, carrying with them the bottle of pills he reported he took prior to the onset of his symptoms. The bottle of supplements was filled to about ¾ of its capacity, with the label indicating that each capsule contained 250mg of Vitamin B17.

Given the persistence of fatigue and rising lactate, the physician decided to perform an internet search on whether any adverse effects were linked to the over-ingestion of vitamin B17. While most sources claimed the supplement was relatively safe, with many ayurvedic webpages praising the vitamin’s numerous benefits, it was soon found that the vitamin had been shown in studies to be associated with the development of cyanide toxicity when taken in large amounts.

However, this toxicity apparently only seldom manifested in individuals who only consumed vitamin B17. Instead, the cases of cyanide toxicities observed occurred more frequently in groups of patients who had concomitant consumption of Vitamin C.

Returning back to the patient, further history taking revealed that the patient had, in fact, consumed vitamin C for the past one month after he had about flu and had failed to mention it earlier as it had ‘slipped his mind at the time.’ Considering the risks evident in the patient’s ingestion history and his worsening fatigue (at 30 minutes after the ED arrival, the patient had now become increasingly somnolent with profuse diaphoresis, maintaining O2 saturation at 94-96% on room air), the decision was made to manage the patient as a case of cyanide toxicity and hydroxycobalamin was administered.

What is Vitamin B17?

Vitamin B17, also known as Amygdalin, is a naturally occurring chemical compound that is found most famously in the seeds of fruits such as apricots, bitter almonds, apples, peaches and plum (1). At the molecular level, amygdalin is formed as a chemical combination of Glucose, Benzaldehyde and Cyanide. The cyanide component in amygdalin can be released by the action of Beta-Glucosidase and Emulsin- both of which are not present in human tissues. However, microorganisms present in human intestinal linings have been found to possess similar enzymes that effectively promote cyanide release from the Amygdalin compound. The resulting cyanide toxicity is therefore almost 40 times more toxic by the oral route when compared with IV injection of the compound (2).

A modified form of amygdalin has been available under the brand name ‘Laetrile’ since the early 1950s as an alternative treatment to fight cancer, though most studies have failed to show any such benefit in humans (3). While the US FDA continues to insist on the drug’s obvious cyanogenic effects, there exist numerous advocates promoting the potential benefits of taking Amygdalin. Despite years of regulation on the original Laetrile supplement, unregulated forms of Amygdalin (or Vitamin B17 as it is often called) continue to circulate the market and are available in most outlets without the need for a prescription.

Since the toxicity of amygdalin depends on intestinal conversion, peak levels of cyanide are usually reached at around 2 hours post-ingestion. A curious phenomenon was evidenced in studies which found that the conversion of amygdalin to cyanide in vitro was further accelerated when amygdalin was ingested with foods containing beta-glucuronidase (such as bean sprouts, peaches, celery, and carrots) or with a concurrent intake of high doses of vitamin C (4,5).

Cyanide Toxicity - Principles & Management

Oral intake of 500 mg of amygdalin may contain up to 30 mg of cyanide (6). A minimum lethal dose of cyanide is approximately 50 mg or 0.5 mg/kg body weight (7). Our patient had ingested eight 250mg tablets, totaling 2000mg of amygdalin, thereby exposing him to a dose of cyanide well above the lethal dose.

Cyanide has a famously dangerous mechanism of toxicity. It binds to the ferric ion on cytochrome oxidase in mitochondria and blocks the electron transport chain, thus halting oxidative metabolism and leading to cell death by interfering with mitochondrial oxygen utilization leading to cell death, hypoxia and lactic acidosis (8). Mild to moderate cases of cyanide toxicity manifest as tachycardia, headache, confusion, nausea, and weakness. Severe cases may present with cyanosis, coma, convulsions, cardiac arrhythmias, cardiac arrest, and death.

Treatment involves addressing the patient’s vitals, oxygen saturation and acidosis as well as administering the appropriate antidote as detailed in the Table below. A sequence of these medications can be incorporated or hydroxycobalamin can be administered alone, as was done in the case above.

Cyanide Toxicity Medication

Medication

Dosage

Mechanism of Action

Notes

Amyl Nitrite pearls
0.3mL (1 amp) inhaled prior to establishing IV
Induces methemoglobinemia (binds cyanide)
First component of cyanide kit Discontinue once IV started
Sodium Nitrite
300mg (10 mg/kg) IV over 3-5 minutes
Induces methemoglobinemia (binds cyanide)
Second component of cyanide kit Do NOT use if suspected concurrent Carbon Monoxide poisoning
Sodium Thiosulfate
12.5 g IV over 10-20 minutes
Binds cyanide to form thiocyanate (less toxic) which is excreted in urine
Third component of cyanide kit
Hydroxycobalamin
5 g IV over 15 minutes
Binds cyanide to form cyanocobalamin (Vitamin B12) which is excreted in urine
Can be used as a single agent May cause transient hypertension

Conclusion

As with most cases of toxic ingestion, the key to effective management is appropriate stabilization followed by rapid identification of the potential toxicity through focused history taking and physical examination of the patient. In cases such as the one outlined above, where the ingested agent is unfamiliar but poses a potential threat, efforts should be made to probe deeper into the potential side effects, interactions and toxicities of such drugs and the Poison Control Center contacted immediately when and where available to expedite successful treatment of affected patients.

For our patient, the decision to administer hydroxycobalamin was followed by admission to the ICU with serial investigations done to monitor for any metabolic derangements. The patient showed remarkable improvement in his symptoms over the course of 24 hours and was eventually discharged in a stable condition.

References and Further Reading

  1. National Center for Biotechnology Information. PubChem Compound Database; CID=656516,
  2. https://pubchem.ncbi.nlm.nih.gov/compound/656516
    http://toxnet.nlm.nih.gov/cgi-bin/sis/search2/r?dbs+hsdb:@term+@DOCNO+3559
  3. Laetrile (Vitamin B17 or Amygdalin): Benefits, Myths and Food Sources, https://www.healthline.com/nutrition/laetrile-vitamin-b17
  4. Bromley J., Hughes B. G. M., Leong D. C. S., Buckley N. A. Life-threatening interaction between complementary medicines: Cyanide toxicity following ingestion of amygdalin and vitamin C. Annals of Pharmacotherapy. 2005;39(9):1566–1569. doi: 10.1345/aph.1E634
  5. Conjoint use of laetrile and megadoses of ascorbic acid in cancer treatment: possible side effects, 1979 Sep;5(9):995-7, PMID: 522711
  6. Newton G. W., Schmidt E. S., Lewis J. P., Conn E., Lawrence R. Amygdalin toxicity studies in rats predict chronic cyanide poisoning in humans. Western Journal of Medicine. 1981;134(2):97–103.
  7. Shragg T. A., Albertson T. E., Fisher C. J., Jr. Cyanide poisoning after bitter almond ingestion. Western Journal of Medicine. 1982;136(1):65–69
  8. Physician Beware: Severe Cyanide Toxicity from Amygdalin Tablets Ingestion- 2017; 2017: 4289527, DOI: 10.1155/2017/4289527
Cite this article as: Mohammad Anzal Rehman, UAE, "A Case Of Cyanide Poisoning From Vitamin B17," in International Emergency Medicine Education Project, July 15, 2019, https://iem-student.org/2019/07/15/a-case-of-cyanide-poisoning-from-vitamin-b17/, date accessed: November 25, 2020

A 32-year-old male with anxiety and tremor

You are working an evening shift during your first year as an Emergency Medicine resident. A new patient shows up on the board. You briefly check his information, and you learn that he is a 32-year-old male with history of alcohol abuse coming into the Emergency Department for anxiety and tremors.

Triage note says in bold: “last drink 50 hours ago.” The patient is tachycardic, hypertensive, and mildly tachypneic. 

You go to see the patient and based on the information you got, you diagnose him with alcohol withdrawal syndrome complicated by withdrawal delirium (delirium tremens). Good! You have a clinical diagnosis, but what does this patient need for workup and management?

Figure 1. DSM-5 Criteria for Alcohol Withdrawal and Delirium. If the patient fulfills the criteria for both the diagnosis of alcohol withdrawal complicated by withdrawal delirium is made.

Pathophysiology

There are two different ethanol action in the central nervous system (CNS) that lead to symptoms of alcohol withdrawal. Overall, alcohol is a central nervous system depressant. It simultaneously increases inhibitory tone via modulation of GABA activity and decreases excitatory tone via modulation of excitatory amino acid activity. In a patient with alcohol abuse disorder, only a constant presence of alcohol keeps the necessary homeostasis. Sudden cessation unmasks the adaptive responses to chronic ethanol use, resulting in overactivity of the central nervous system.

Gamma-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. Highly specific binding sites for ethanol are found on the GABA receptor complex. Chronic ethanol use induces GABA receptor insensitivity to GABA resulting in a need for a stronger inhibitory stimulus to maintain a constant inhibitory tone. As alcohol tolerance develops, the individual retains arousal at alcohol concentrations that would normally produce lethargy or even coma in people who do not have alcohol use disorder. Sudden cessation of alcohol intake or a reduction from chronically elevated concentrations results in decreased inhibitory tone due to the lack of inhibitory effects of ethanol.

Glutamate is one of the major excitatory amino acids. When glutamate binds to the N-methyl-D-aspartate (NMDA) receptor, calcium influx leads to neuronal excitation by binding to the glycine receptor on the NMDA complex. Ethanol inhibits glutamate-induced excitation. Adaption occurs by increasing the number of glutamate receptors in an attempt to maintain a normal state of arousal.

Figure 2. Inhibitory and excitatory balance in a healthy individual.
Inhibitory and excitatory balance in an individual with chronic alcohol abuse.
Figure 3. Inhibitory and excitatory balance in an individual with chronic alcohol abuse. The constant presence of alcohol is needed to maintain inhibitory tone on insensitive GABA receptors and to inhibit excitatory tone on upregulated NMDA receptors.
Loss of the inhibitory and excitatory balance after alcohol cessation.
Figure 4. Loss of the inhibitory and excitatory balance after alcohol cessation. Upregulated NMDA receptors lead overexcitation, and insensitive GABA receptors are not enough to counteract that. Alcohol withdrawal symptoms ensue.

Differential Diagnosis

Alcohol withdrawal remains a clinical diagnosis. The severity of presentation can be assessed using a clinical assessment scale called Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) that can be found on MD Calc.

In some cases, several additional tests might be needed to rule out other conditions that mimic or coexist with alcohol withdrawal syndrome. This is especially true when the patient has altered mental status and fever. Conditions such as infection (e.g., meningitis), trauma (e.g., intracranial hemorrhage), metabolic abnormalities, drug overdose, hepatic failure, and gastrointestinal bleeding can mimic or coexist with alcohol withdrawal. Also, it is of marked importance to try to understand why the patient stopped consuming alcohol. If you establish that he wanted to get sober, that is great, you or the admitting team can help setting up rehab for him after the acute problems are controlled. However, you should get suspicious if there is not a clear cause for the abrupt cessation of alcohol intake since it could be an acute condition being masked by the withdrawal syndrome.

Initial workup might include:

  • Point of care glucose

  • CBC and platelets

  • Sodium, potassium, chloride, bicarbonate, BUN, creatinine

  • Calcium, magnesium, and phosphorus

  • Total protein, albumin, total bilirubin, AST, ALT, and alkaline phosphatase, and lipase

  • Creatine kinase

  • Chest x-ray to rule out simultaneous pneumonia

  • Consider head CT and lumbar puncture, if there are any findings concerning for trauma, intracranial hemorrhage, or CNS infections

  • Consider drug screen if concern for co-ingestion

Figure 5. The differential diagnosis for alcohol withdrawal. It is important to not anchor on this diagnosis and to look for mimics and conditions that might coexist with it.

Supportive Care

As important as proving control of the patient’s withdrawal symptoms is to provide high-quality supportive care, which includes:

  • Placement in a quiet and protective environment

  • Preference for chemical sedation over physical restraints, which should be removed as soon as adequate chemical sedation is achieved because resistance against restraints can increase temperature, produce rhabdomyolysis, and cause physical injury

  • IV fluids

  • Thiamine and glucose should be administered in order to prevent or treat Wernicke encephalopathy

  • Multivitamins containing or supplemented with folate should be given routinely

  • Deficiencies of glucose, potassium, magnesium, and phosphate should be corrected as needed

  • Nothing by mouth in the early stages of treatment to prevent aspiration

  • Patients considered at high risk for complications should be monitored in an intensive care unit

  • Consider ICU admission and EtCO2 monitoring in those patients with severe alcohol withdrawal per CIWA-Ar

Symptomatic Treatment

The basis for the treatment of alcohol withdrawal is CNS depressants, such as benzodiazepines, with a treatment goal of Richmond Agitation and Sedation Scale (RASS) -1 and HR < 110. No single drug benzodiazepine is superior to another. A common treatment strategy is to use a benzodiazepine of choice and give escalating doses until symptomatic control or until you reach criteria for refractory alcohol withdrawal.

Figure 6. Two common initial treatment strategies for alcohol withdrawal.

Refractory Withdrawal Delirium

Some patients have refractory delirium tremens (DT) despite treatment with high-dose benzodiazepines. Refractory DT is not clearly defined. It may be present if symptoms of severe withdrawal are not controlled adequately after the IV administration of more than 50 mg of diazepam or 10 mg of lorazepam during the first hour of treatment, or 200 mg of diazepam or 40 mg of lorazepam during the initial three to four hours of treatment. In such cases, as with any dangerous toxicologic disorder, you should obtain assistance from a medical toxicologist or poison control center. In case you diagnose your patient with alcohol withdrawal refractory to benzodiazepine treatment, you should have a few other options in your treatment arsenal.

Summary of sedation strategy.
Figure 7. Summary of sedation strategy. Initial treatment with benzodiazepines in escalating doses. If good response, keep regimen titrated to treatment goals. If no response, consider refractory withdrawal delirium and other pharmacologic options. If no response after secondary treatment, consider intubation with propofol.

Phenobarbital

There are case reports of up to 2000 mg of Phenobarbital administered orally or intravenously on the first day in patients with alcohol withdrawal delirium. Consider giving phenobarbital 130 to 260 mg IV, repeated every 15 to 20 minutes, until symptoms are controlled. Also, you can consider administering Phenobarbital earlier in the disease course. A randomized trial of 102 patients presenting to the emergency department with acute alcohol withdrawal, those treated with lorazepam and a single dose of Phenobarbital had substantially lower ICU admission rates compared with those treated with lorazepam alone (8 versus 25 percent).

Dexmetomedine

Another adjunctive medication for alcohol withdrawal is dexmedetomidine, an α2-adrenergic agonist that is used to provoke a state in which the patient is sedated but arousable, with a decreased sympathetic tone. Doses up to 0.7 μg per kilogram per hour have been administered in patients who do not have a good response to benzodiazepines. Heart block is a contraindication to this drug since it can cause bradycardia. In case it is given, blood pressure and heart rate must be closely monitored.

Propofol and Intubation

In patients who do not have a response to high doses of benzodiazepines (especially patients who are intubated), propofol may be administered to reach symptomatic control.

Take home points.
Figure 8. Take home points.

Further Reading

References

  • Isbell H, Fraser HF, Wilker A, et al. An experimental study of the etiology of rum fits and delirium tremens. Q J Stud Alcohol 1955; 16:1.
  • Mihic SJ, Ye Q, Wick MJ, et al. Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature 1997; 389:385.
  • Morrow AL, Suzdak PD, Karanian JW, Paul SM. Chronic ethanol administration alters gamma-aminobutyric acid, pentobarbital and ethanol-mediated 36Cl- uptake in cerebral cortical synaptoneurosomes. J Pharmacol Exp Ther 1988; 246:158.
  • Hoffman PL, Grant KA, Snell LD, et al. NMDA receptors: role in ethanol withdrawal seizures. Ann N Y Acad Sci 1992; 654:52.
  • Hecksel KA, Bostwick JM, Jaeger TM, Cha SS. Inappropriate use of symptom-triggered therapy for alcohol withdrawal in the general hospital. Mayo Clin Proc 2008; 83:274.
  • Hack JB, Hoffman RS. Thiamine before glucose to prevent Wernicke encephalopathy: examining the conventional wisdom. JAMA 1998; 279:583.
  • Hoffman RS, Goldfrank LR. The poisoned patient with altered consciousness. Controversies in the use of a ‘coma cocktail’. JAMA 1995; 274:562.
  • Hoffman RS, Goldfrank LR. Ethanol-associated metabolic disorders. Emerg Med Clin North Am 1989; 7:943.
  • Mainerova B, Prasko J, Latalova K, et al. Alcohol withdrawal delirium — diagnosis, course and treatment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013;157:1-9
  • Mayo-Smith MF, Beecher LH, Fischer TL, et al. Management of alcohol withdrawal delirium: an evidence-based practice guideline. Arch Intern Med 2004;164:1405-1412
  • Amato L, Minozzi S, Vecchi S, Davoli M. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev2010;3:CD005063-CD005063
  • Hjermø I, Anderson JE, Fink-Jensen A, Allerup P, Ulrichsen J. Phenobarbital versus diazepam for delirium tremens — a retrospective study. Dan Med Bull 2010;57:A4169-A4169
  • DeCarolis DD, Rice KL, Ho L, Willenbring ML, Cassaro S. Symptom-driven lorazepam protocol for treatment of severe alcohol withdrawal delirium in the intensive care unit. Pharmacotherapy 2007;27:510-518
  • DeBellis R, Smith BS, Choi S, Malloy M. Management of delirium tremens. J Intensive Care Med 2005;20:164-173
  • Cagetti E, Liang J, Spigelman I, Olsen RW. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol 2003; 63:53.
  • Nolop KB, Natow A. Unprecedented sedative requirements during delirium tremens. Crit Care Med 1985; 13:246.
  • Hack JB, Hoffmann RS, Nelson LS. Resistant alcohol withdrawal: does an unexpectedly large sedative requirement identify these patients early? J Med Toxicol 2006; 2:55.
  • Rosenson J, Clements C, Simon B, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med 2013; 44:592.
  • Rayner SG, Weinert CR, Peng H, Jepsen S, Broccard AF. Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU. Ann Intensive Care 2012;2:12-12
  • Muzyk AJ, Fowler JA, Norwood DK, Chilipko A. Role of α2-agonists in the treatment of acute alcohol withdrawal. Ann Pharmacother 2011;45:649-657
  • Thomson AD, Cook CCH, Touquet R, Henry JA. The Royal College of Physicians report on alcohol: guidelines for managing Wernicke’s encephalopathy in the accident and emergency department. Alcohol Alcohol 2002;37:513-521
  • Koethe D, Juelicher A, Nolden BM, et al. Oxcarbazepine — efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study. Alcohol Clin Exp Res 2007;31:1188-1194
Cite this article as: Henrique Puls, Brasil, "A 32-year-old male with anxiety and tremor," in International Emergency Medicine Education Project, June 3, 2019, https://iem-student.org/2019/06/03/a-32-year-old-male-with-anxiety-and-tremor/, date accessed: November 25, 2020