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Is Ondansetron for Nausea and Vomiting Prophylaxis Necessary with Opioids?

prophylactic ondansetron with opioids example 4+4
Ondansetron is the most documented medication given in emergency departments (ED) throughout the United States [1]. We have all heard someone ask, “Can I get an order for 4 and 4 for this patient?” in reference to 4 mg of IV morphine and 4 mg of IV ondansetron. It has become common practice in many institutions to provide a prophylactic antiemetic prior to administering an IV opioid.

Logic for giving ondansetron with opioid

This dual therapy seems to make initial sense because all opioids carry a FDA warning that nausea may occur [2]. So why not administer an antiemetic to prevent it? Opioids cause nausea and vomiting due to its interaction on the chemoreceptor trigger zone (CTZ), increased vestibular sensitivity, and hindered gastric emptying [3]. The logic is to provide these patients with a 5-HT3 antagonist (i.e., ondansetron) to inhibit the opioid from exerting emetogenic properties on 5-HT3 receptors in the CTZ and prevent nausea and/or vomiting.

How common is nausea and vomiting associated with IV opioids?

Multiple studies illustrate that morphine-induced nausea and vomiting is low, ranging from 2.0–20.2% in ED patients [4-9]. When discussing with ED nurses, nausea and vomiting are anecdotally associated with how quickly the IV opioid is administered and generally occurs within 5 minutes of administration.

So we should give IV ondansetron to prevent this, right? A common misconception with IV ondansetron is its onset of action. In fact, it can take anywhere between 27-34 minutes before there is a 50% decrease in nausea severity following the administration of ondansetron [10, 11]. This begs the question, does it really make sense to provide prophylactic antiemetics with IV opioids?

Literature Review

StudyInterventionOutcomeConclusion
Bradshaw et al. [5]

RCT- double blinded

Performed in United Kingdom

IV morphine + placebo (n=136)

IV morphine + metoclopramide 10 mg (n=123)

N/V between the 2 groups was not statistically significant (p=0.3).

Overall incidence of N/V was low in both treatment groups (3.7% in placebo and 1.6% metoclopramide)

Pre-treating patients with metoclopramide was not necessary.

Overall N/V associated with IV morphine was very low and recommended using antiemetics for patients who develop N/V.

Bhowmik et al. [8]

RCT, double blinded

Performed in India

IV morphine + placebo (n=53)

IV morphine + promethazine (n=54)

IV morphine + ramosetron (n=54)

IV morphine + metoclopramide (n=54)

Overall incidence of N/V was low in all treatment groups (9.4% ramosetron, 18.5% metoclopramide, 10.2% in promethazine and 6.2% in placebo)

Rate of N/V was not statistically significant between any of the groups.

 Patients should receive antiemetic therapy only if experience N/V and not as a prophylactic agent with IV opioids.

Patients that received (morphine + placebo) had less N/V compared to other treatment groups; however, NOT statistically significant.

Sussan et al. [9]

Randomized, double- masked multicenter trial

Performed in 9 countries

Investigated 2,574 patients that received IV opioids and randomized 520 patients that developed N/V associated with IV opioids.

Group 1: placebo (n=94)

Group 2: ondansetron 8 mg (n=214)

Group 3: ondansetron 16 mg (n=211)

Resolution of N/V was statistically more significant (p < 0.001) when comparing ondansetron therapy with placebo.

Group 1: 45.7% N/V resolved

Group 2: 62.3% N/V resolved

Group 3: 68.7% N/V resolved

The best practice seems to treat patients’ N/V after development in patients that receive IV opioids.

Trial determined the prevalence of N/V is minimal and exposing patients to medication they do not need puts them at risk for additional adverse drug reactions.

Each of the 3 trials concluded that there was no statistical significance in outcomes when adding prophylactic antiemetics with IV opioids. After these institutions analyzed their findings, the investigators at their respective institutions made it common practice for patients to only receive antiemetics AFTER a patient developed nausea or vomiting.

Prophylactic ondansetron practice

So why is ondansetron still commonly used to pre-treat patients that receive IV opioids in the ED?

The limited literature primarily focused on these anti-emetic agents: metoclopramide, promethazine, and ramosetron (5-HT3 antagonist). Literature related to specifically ondansetron is minimal.

Two randomized, placebo-controlled studies comparing ondansetron, metoclopramide, and saline in ED patients complaining of nausea showed no clinically important difference in the reduction of nausea between treatments and placebo [12, 13]. Yet in the ED, we still order ondansetron more than any other medication.

Some nerd (me!) put together a prospective multiple-site study (n=133) at 2 academic medical institutions where patients were administered IV opioids, with or without IV ondansetron [14]. Patients were observed for nausea and vomiting at baseline, 5 minutes, and 30 minutes after opioid administration, and then for a total of 2 hours. The results showed that 17.3% of patients developed nausea, with no significant difference in the rate of nausea, emesis, or the need for rescue antiemetics between the group receiving ondansetron and the group receiving opioids alone.

Of note, ondansetron is not FDA approved for the treatment or prophylaxis of acute nausea and/or vomiting (N/V) outside of chemotherapy, radiation, and postoperative use. It also, not surprisingly, has side effects!

Take Home Point

  1. Concurrent treatment with anti-emetics (including ondansetron) is unnecessary, increases costs, and adds potential for adverse drug reactions.
  2. The next time the request for “4 + 4” comes through, consider holding off on the unnecessary ondansetron with your IV opioid order.
  3. You can use this isopropyl alchohol vapor inhalation trick of the trade for those 2-20% of patients that do develop nausea.

References

  1. National Hospital Ambulatory Medical Care Survey: 2011 Emergency Department Summary. Accessed 19 Dec 2024.
  2. Red Book: pharmacy’s fundamental reference. Montvale, NJ: Thompson Healthcare Inc.; 2010
  3. Smith H, Smith J, Seidner P. Opioid-induced nausea and vomiting. Annals of Palliative Medicine 2012;1(2):121-129
  4. Paoloni R, Talbot-Stern J. Low incidence of nausea and vomiting with intravenous opioid analgesia in the ED. Am J Emerg Med 2002;20:604-608.
  5. Bradshaw M, A Sen. Use of prophylactic antiemetic with morphine in acute pain: randomized controlled trial. Emerg Med J 2006; 23:210-212.
  6. Talbot-Stern J, Paoloni R. Prophylactic metoclopramide is unnecessary with intravenous analgesia in the ED. Am J Emerg Med 2000;18(6):653-7.
  7. Lambie B, Chambers J, Herbison P. The role of prophylactic anti-emetic therapy in emergency department patients receiving intravenous morphine for musculoskeletal trauma. Emer Med 1990; 11(4): 240-243.
  8. Bhowmik A, Dasgupta I, Barua S, et al. Evaluation of the need of prophylactic antiemetic with injection morphine in treating acute musculoskeletal pain in the Indian population. IJAR 2014;2:53-58.
  9. Sussan G, Shurman J, Creed M, et al. Intravenous ondansetron for the control of opioid-induced nausea and vomiting. Clinical Therapeutic. 1999; 21:1216-1227.
  10. Cotton J, Rowell L, Hood R, et al. A comparative analysis of isopropyl alcohol and ondansetron in the treatment of postoperative nausea and vomiting from the hospital setting to the home. AANA J. 2007; 75(1):21-6.
  11. Winston A, Rinehart R, Riley G, et al. Comparison of inhaled isopropyl alcohol and intravenous ondansetron for treatment of postoperative nausea. AANA J. 2003; 71(2):127-32.
  12. Barrett TW, DiPersio DM, Jenkins CA, et al. A randomized, placebo-controlled trial of ondansetron, metoclopramide, and promethazine in adults. Am J Emerg Med. 2011 Mar;29(3):247-55.
  13. Egerton-Warburton D, Meek R, Mee MJ, et al. Antiemetic use for nausea and vomiting in adult emergency department patients: randomized controlled trial comparing ondansetron, metoclopramide, and placebo. Ann Emerg Med. 2014 Nov;64(5):526-532.
  14. Culver MA, Richards EC, Jarrell DH, et al. Use of Prophylactic Ondansetron With Intravenous Opioids in Emergency Department Patients: A Prospective Observational Pilot Study. J Emerg Med. 2017;53(5):629-634. PMID 28987314. DOI
By |2025-01-28T13:44:31-08:00Feb 26, 2025|Capsules, EM Pharmacy Pearls, PEM Pearls, Tox & Medications|
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SAEM Clinical Images Series: When it is Not Just a Knot

knot

A 12-year-old male with a history of hydrocephalus status post ventriculoperitoneal (VP) shunt placement presented with an abdominal “knot.” The patient’s mother noticed the knot two days ago, on the right anterolateral thorax, which has steadily been increasing in size. The patient had no known trauma to the area or had been bitten or stung by any insect. He has otherwise been complaining of a headache, generalized, without positional changes, improved with home acetaminophen, ice pack, and rest. There were otherwise no associated vision changes, nausea, vomiting, mental status changes, or fever.

Vitals: T-36.2°C; HR 74 bpm; BP 144/75 mm Hg; RR 20; O2 Sat 96% RA

General: Well-appearing teenager in NAD.

HEENT: NC/AT. PERRL approximately 2-3 mm bilaterally. EOMI.

Neck: Supple, no meningismus.

Chest Wall: Induration to the right anterolateral thorax 5 cm x 4 cm without erythema, fluctuance, or drainage, non-tender to palpation.

Neurological: Alert. No focal neurological deficit observed.

Normal

The cause of the knot is subcutaneous cerebrospinal fluid from a shunt malfunction. The ultrasound images show characteristic “cobblestoning,” indicating fluid in the subcutaneous tissue, around a linear hyperechoic object, the catheter of the VP shunt. On the plain film imaging, a disconnect was found between the thoracic and abdominal portions of the VP shunt. Up to 80% of patients with VP shunts will have experienced a shunt malfunction after 12 years, according to one study, with fractured tubing causing shunt failure in around 15% of all cases (1).

Nausea, vomiting, headache, irritability, or decreased mental status are common but nonspecific findings in shunt malfunction. Pediatric patients may present with other signs such as bulging fontanelles, increasing head circumference, or feeding and behavioral changes. An increase in the interval ventricular size can be seen in neuroimaging but can be absent in as many as 20% of patients (2). If there is a high degree of clinical suspicion for shunt malfunction, normal or unchanged neuroimaging should not preclude neurosurgical consultation.

Take-Home Points

  • In the United States, mechanical causes of VP shunt malfunction are the most common presentation, such as catheter obstruction, fracture along the clavicle or ribs, degradation of tubing, and migration of the distal catheter due to changes in height or weight.
  • Rarely, patients can develop an accumulation of CSF at the distal catheter of the VP shunt due to migration into the abdominal wall forming an abdominal pseudocyst.
  • In patients with VP shunts, abdominal complications should be considered as a sign of shunt malfunction.
  • Consider pertinent physical exam findings and POCUS to confirm the diagnosis of shunt malfunction at the distal catheter.

  • Sainte-Rose C, Piatt JH, Renier D, Pierre-Kahn A, Hirsch JF, Hoffman HJ, Humphreys RP, Hendrick EB. Mechanical complications in shunts. Pediatr Neurosurg. 1991-1992;17(1):2-9. doi: 10.1159/000120557. PMID: 1811706.

  • Reynolds RA, Ahluwalia R, Krishnan V, Kelly KA, Lee J, Waldrop RP, Guidry B, Hengartner AC, McCroskey J, Arynchyna A, Staulcup S, Chen H, Hankinson TC, Rocque BG, Shannon CN, Naftel R. Risk factors for unchanged ventricles during pediatric shunt malfunction. J Neurosurg Pediatr. 2021 Sep 24;28(6):703-709. doi: 10.3171/2021.6.PEDS2125. PMID: 34560626.

Copyright

Images and cases from the Society of Academic Emergency Medicine (SAEM) Clinical Images Exhibit at the 2023 SAEM Annual Meeting | Copyrighted by SAEM 2023 – all rights reserved. View other cases from this Clinical Image Series on ALiEM.

By |2025-02-19T12:57:12-08:00Feb 21, 2025|Neurology, Pediatrics, SAEM Clinical Images, Ultrasound|
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SAEM Clinical Images Series: A Rare Gastrointestinal Complication of an Endocrine Emergency

A 54-year-old woman with a history of hypothyroidism, diabetes mellitus type II, COPD, asthma, anxiety, and depression presented to the emergency department via EMS with three days of fatigue, weakness, chills, and shortness of breath without chest pain or cough. Symptoms had been progressively worsening, and she stated she felt as if she could not move her body on presentation. She also noted diarrhea without abdominal pain, melena, or hematochezia. Just prior to arrival the patient’s daughter thought she looked paler and shorter of breath and called EMS after a near syncopal episode. EMS reported that the family was concerned that the patient’s blood glucose level was low. Blood glucose upon EMS arrival was 90 and rose to 150 following their administration of oral glucose. The patient denied fever, recent sick contacts, urinary changes, hematuria, or leg swelling. She reported two missed doses of levothyroxine which was prescribed at a dose of 25 mcg daily. No recent antibiotic use reported.

 

ogilvie syndrome

Vitals: Temp 36.4°C; BP 106/64 mmHg; HR 62 bpm; Resp 16/min; SpO2 96% on RA

General: Patient drowsy, slow to answer questions, sitting with eyes closed. No obvious distress.

Skin: Warm and dry.

Cardiovascular: Regular rate and rhythm without murmur.

Respiratory: Lungs clear to auscultation bilaterally. No respiratory distress.

Abdomen: Soft, non-distended, normal bowel sounds, diffuse abdominal discomfort to palpation, which she states is chronic.

Neurological: Oriented to person, place, time. CN II-XII intact. No focal neurological deficit observed, strength 4+/5 throughout able to hold all extremities up when placed above the body.

Extremities: No obvious swelling.

CBC: Hb 11.5, WBC 9.5, Plt 186

BMP: Na 141, K 3.8, Cl 105, CO2 24, BUN 17, Cr 1.3

LFTs: AST 20, ALT 11, Bili 0.4

VBG: pH 7.28, PCO2 60, HCO2 28

Mg: 1.7

CK: 333

TSH: 196.80

The abdominal CT scan demonstrates multiple fluid-filled mildly dilated loops of large bowel with air-fluid levels, some minimally dilated loops of small bowel, and no clear transition point identified which is concerning for developing colonic pseudo-obstruction (Ogilvie Syndrome). There are many predisposing factors that may cause Ogilvie Syndrome including recent surgery, infection, trauma, respiratory failure, cancer, and other metabolic conditions.

Given our patient’s history of hypothyroidism with missed doses of levothyroxine and an elevated TSH her cause of Ogilvie syndrome is most likely hypothyroidism. This is also known as myxedema ileus, a rare entity. Management of myxedema ileus consists of bowel decompression with a nasogastric tube and treatment of the hypothyroid condition. In our case, the patient received 200 mcg of levothyroxine, and 12.5 mcg of liothyronine while undergoing further endocrinologic workup

Take-Home Points

  • In patients with a history of hypothyroidism presenting with gastrointestinal concerns, myxedema ileus, while not common, should be considered.
  • Colonic pseudo-obstruction (Ogilvie syndrome) has many causes and the radiographic appearance of a bowel obstruction without an obvious transition point.
  • Myxedema ileus should be managed with bowel decompression and treatment of the underlying hypothyroidism. ICU level care is often needed for this severe endocrine emergency

  • Saunders MD. Acute colonic pseudo-obstruction. Best Pract Res Clin Gastroenterol. 2007;21(4):671-87. doi: 10.1016/j.bpg.2007.03.001. PMID: 17643908.

  • Vanek VW, Al-Salti M. Acute pseudo-obstruction of the colon (Ogilvie’s syndrome). An analysis of 400 cases. Dis Colon Rectum. 1986 Mar;29(3):203-10. doi: 10.1007/BF02555027. PMID: 3753674.

Copyright

Images and cases from the Society of Academic Emergency Medicine (SAEM) Clinical Images Exhibit at the 2023 SAEM Annual Meeting | Copyrighted by SAEM 2023 – all rights reserved. View other cases from this Clinical Image Series on ALiEM.

By |2025-02-19T12:24:25-08:00Feb 21, 2025|Endocrine-Metabolic, Gastrointestinal, SAEM Clinical Images|
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SAEM Clinical Images Series: Male Weightlifter with Chest Pain

hyperacute

An otherwise healthy 45-year-old male presented to the emergency department (ED) with substernal chest pain radiating down his left arm over the previous two days. On the first day of symptoms, his pain began several hours after using a new pre-workout supplement and weightlifting. The symptoms lasted for a few hours and self-resolved. The pain returned the following day under the same conditions, although this time persistent, which brought him in for evaluation. Associated symptoms included shortness of breath, nausea, and one episode of emesis. He denied pleuritic pain, lower extremity edema, hemoptysis, syncope, cough, or chest wall trauma. On further history, he reported prior use of anabolic steroids, with the last being six weeks prior to presentation. It was unclear what were the contents of the pre-workout supplement, but he denied any tobacco or illicit drug use. Notably, he had a significant family history of heart disease with his father having undergone coronary bypass at age 47. His initial ECG (Image 1) and interval ECG (Image 2) are shown.

 

Vitals: T 36.5°C; HR 74; RR 16; BP 161/107; SpO2 98% on RA

General: Uncomfortable and diaphoretic in moderate distress.

Cardiovascular: Normal rate and rhythm, no murmurs. Equal radial and PT pulses bilaterally.

Pulmonary: Non-labored breathing, lungs CTA bilaterally with equal breath sounds.

Extremities: Lower extremities without significant edema, symmetric in size.

Neuro: Alert and oriented, neurologically intact.

Complete blood count (CBC): mild polycythemia (Hgb 19.0 g/dL) and leukocytosis (WBC 10.1 x 10(9)/L)

Basic metabolic panel (BMP): Cr 1.22 mg/dL, GFR 75 mL/min/BSA, K 4.5 mmol/L

Troponin T, 5th generation: 97 ng/L (ref. range: <=15 mg/L)

Acute coronary syndrome (ACS) with myocardial infarction. Hyperacute T waves are seen on the initial ECG.

This patient’s initial ECG (Image 1) raised concern for hyperacute T waves, which are often described as broad-based with a large amplitude. This subtle finding is difficult to differentiate from normal variants, hypertrophy, or hyperkalemia (1,2). Hyperacute T waves have been considered an early sign of acute coronary occlusion, however, current literature is mixed regarding their clinical utility, particularly given the lack of a formal ECG definition (3,4,5). The American College of Cardiology (ACC) recommends obtaining serial ECGs in patients with hyperacute T waves to assess for progression to STEMI (3). In this patient’s case, interventional cardiology was consulted, and the patient was given aspirin and sublingual nitroglycerin. He developed worsened chest pain, and a repeat ECG showed no significant changes. Shortly after, he went into ventricular fibrillation and cardiac arrest. A post-ROSC ECG (Image 2) showed concave ST elevations in the anterolateral leads with reciprocal ST depressions in the inferior leads, meeting STEMI criteria. Coronary angiography showed severe multivessel disease and 100% occlusion of the left anterior descending (LAD) artery. A drug-eluting stent was placed, and the patient was discharged home one week later with an intact neurologic status.

History of anabolic steroid use, pre-workout supplementation, and significant family history of CAD. In more recent years, the number of younger patients (35-54 years) hospitalized for ACS has increased (6). This trend is believed to be related to the increased use of illicit drugs, including marijuana and androgenic-anabolic steroids (AAS) (6). AAS is known to increase the risk of cardiac hypertrophy, ACS, and sudden cardiac death by increasing lipoprotein production, causing intimal hyperplasia of coronary arteries, and increasing clotting factors leading to a procoagulant state (7,8). Consensus on the adverse effects and overall safety of pre-workout supplements remains under debate and they remain unregulated by the FDA. Studies suggest that synephrine, a common product found in pre-workout supplements, may raise safety concerns due to its androgenic properties (9). A 2023 systematic review of adverse outcomes related to synephrine found associations with cardiomyopathy, ACS, arrhythmias, and cerebrovascular disease (9,10).

Take-Home Points

  • Hyperacute T waves, although not diagnostic in isolation, may be an early marker for occlusion myocardial infarction and if seen, serial ECGs should be performed.

  • A high degree of clinical suspicion for ACS should be maintained among patients with a history of androgenic-anabolic steroid use, even in young and otherwise healthy individuals.

  • Pre-workout supplements, especially those that contain the compound synephrine have been associated with ACS and other cardiovascular pathology.

  • Somers MP, Brady WJ, Perron AD, et al. The prominent T wave: electrocardiographic differential diagnosis. Am J Emerg Med 2002 May;20(3):243-51

  • Levis JT. ECG Diagnosis: Hyperacute T Waves. Perm J. 2015 Summer;19(3):79. doi: 10.7812/TPP/14-243. PMID:26176573; PMCID: PMC4500486.

  • Writing Committee; Kontos MC, de Lemos JA, Deitelzweig SB, Diercks DB, Gore MO, Hess EP, McCarthy CP, McCord JK, Musey PI Jr, Villines TC, Wright LJ. 2022 ACC Expert Consensus Decision Pathway on the Evaluation and Disposition of Acute Chest Pain in the Emergency Department: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022 Nov 15;80(20):1925-1960. doi: 10.1016/j.jacc.2022.08.750. Epub 2022 Oct 11. PMID: 36241466; PMCID: PMC10691881.

  • Koechlin L, Strebel I, Zimmermann T, Nestelberger T, Walter J, Lopez-Ayala P, Boeddinghaus J, Shrestha S, Arslani K, Stefanelli S, Reuthebuch B, Wussler D, Ratmann PD, Christ M, Badertscher P, Wildi K, Giménez MR, Gualandro DM, Miró Ò, Fuenzalida C, Martin-Sanchez FJ, Kawecki D, Bürgler F, Keller DI, Abächerli R, Reuthebuch O, Eckstein FS, Twerenbold R, Reichlin T, Mueller C; APACE investigators. Hyperacute T Wave in the Early Diagnosis of Acute Myocardial Infarction. Ann Emerg Med. 2023 Aug;82(2):194-202. doi: 10.1016/j.annemergmed.2022.12.003. Epub 2023 Feb 10. PMID: 36774205.

  • Smith SW, Meyers HP. Hyperacute T-waves Can Be a Useful Sign of Occlusion Myocardial Infarction if Appropriately Defined. Ann Emerg Med. 2023 Aug;82(2):203-206. doi: 10.1016/j.annemergmed.2023.01.011. Epub 2023 Mar 3. PMID: 36872197.

  • Bhatt DL, Lopes RD, Harrington RA. Diagnosis and Treatment of Acute Coronary Syndromes: A Review. JAMA. 2022;327(7):662-675.

  • Melchert RB, Welder AA. Cardiovascular effects of androgenic-anabolic steroids. Med Sci Sports Exerc. 1995;27(9):1252-1262.

  • Pope HG, Jr., Kanayama G, Athey A, Ryan E, Hudson JI, Baggish A. The lifetime prevalence of anabolic-androgenic steroid use and dependence in Americans: current best estimates. Am J Addict. 2014;23(4):371-377.

  • de Jonge MLL, Kieviet LC, Sierts M, Egberink LB, van der Heyden MAG. Review of Case Reports on Adverse Events Related to Pre-workout Supplements Containing Synephrine. Cardiovasc Toxicol. 2023 Jan;23(1):1-9. doi: 10.1007/s12012-022-09777-z. Epub 2023 Jan 13. PMID: 36639595; PMCID: PMC9859859.

  • Flo FJ, Kanu O, Teleb M, Chen Y, Siddiqui T. Anabolic androgenic steroid-induced acute myocardial infarction with multiorgan failure. Proc (Bayl Univ Med Cent). 2018;31(3):334-336

Copyright

Images and cases from the Society of Academic Emergency Medicine (SAEM) Clinical Images Exhibit at the 2023 SAEM Annual Meeting | Copyrighted by SAEM 2023 – all rights reserved. View other cases from this Clinical Image Series on ALiEM.

By |2025-01-30T10:12:40-08:00Feb 7, 2025|Cardiovascular, ECG, SAEM Clinical Images|
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ACMT Toxicology Visual Pearl: Hiss-teria Averted

snake

What is the predominant clinical effect of envenomation by this snake?

  1. Acute hepatic failure leading to coagulopathy
  2. Direct cardiotoxicity leading to arrhythmias
  3. Profound neuromuscular paralysis
  4. Rapid onset of shock and multisystem organ failure

[Image courtesy of iStock. ID: 1311554579]

(more…)

By |2025-01-30T07:22:05-08:00Feb 5, 2025|ACMT Visual Pearls, Capsules, Expert Peer Reviewed (Clinical), PEM Pearls, Tox & Medications|
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