Category: Treatment

Emergency Department Triage (2024)

~ iEM Education Project Team ~ Leave a comment

by Priya Arumuganathan and Scott Findley

Authors
Listen

Introduction

Triage is the process of sorting patients by severity of illness to ensure care is administered in a timely fashion according to each patient’s need. When specifically applied to the emergency department, “Emergency Department (ED) Triage” is used to quickly assess, risk-stratify, and manage incoming patients before their complete evaluation. A triage process allows systems to safely operate an influx of multiple patients with varying acuity levels in situations when clinical demand exceeds capacity. Formal triage systems have been employed since as early as the 19th century in warfare settings to effectively handle the growing amounts of field casualties [1].

Today, emergency triage can be generally separated into three distinct phases: prehospital triage, triage at the scene, and emergency department triage. Many different types of triage systems have been developed and implemented worldwide [2]. In this section, we will focus on emergency department triage and some of the most well-known triage systems globally.

Performing a Rapid Triage Assessment

The “rapid triage assessment” is essential to any triage system. Those performing the rapid triage assessment should have some clinical experience and a keen eye to quickly identify patients who need to be seen urgently. The goal of triage is to determine which patients need immediate attention, which patients can wait to be seen, and to manage large patient volumes safely. To accomplish this, one must gather pertinent history and physical exam findings quickly and efficiently.

Performing a Focused History

Obtaining a quick and focused history is of utmost importance during the rapid triage assessment. To summarize, providers must be able to get symptoms pertinent to the patient’s presentation, any relevant events leading to their presentation, and pertinent past medical history and allergies. One mnemonic that is useful and used by many for history-gathering is SAMPLE (as below) [3]:

The SAMPLE mnemonic is a structured method for gathering key clinical information during an emergency assessment. It serves as a framework for emergency medical personnel to obtain essential details quickly and efficiently, allowing them to prioritize care and decide on the best course of action. Each component of the mnemonic corresponds to a specific area of focus in history-gathering, which is vital for rapid triage in the emergency department or pre-hospital setting. Below is a more detailed breakdown of each element:

S – Signs & Symptoms
The first and most immediate part of the assessment focuses on the patient’s presenting signs and symptoms. These may include both subjective (what the patient describes) and objective (what the healthcare provider observes) data. For example, a patient may report chest pain, difficulty breathing, or nausea, while a provider might note abnormal vital signs or physical findings. It’s crucial to obtain a clear description of the symptoms, including onset, duration, intensity, and any factors that may have worsened or alleviated them. Understanding the signs and symptoms will help determine the severity of the condition and direct the urgency of intervention.

A – Allergies
Gathering information about any known allergies is vital in guiding treatment decisions, especially in emergencies where medications or interventions are required quickly. For example, if a patient has a known allergy to penicillin, it is essential to avoid using antibiotics in that class. Allergies to food, medications, environmental triggers, and latex should all be considered. In addition, healthcare providers should be mindful of potential allergic reactions that could complicate the management of the patient’s condition.

M – Medications
A comprehensive medication history helps identify substances that may impact the patient’s current clinical situation. This includes prescribed medications, over-the-counter drugs, supplements, and any recent changes to a medication regimen. For example, a patient taking blood thinners such as warfarin may require careful monitoring for signs of bleeding, while those on insulin may need their blood sugar levels closely monitored. Knowledge of recent changes, doses, and the possibility of drug interactions is crucial in the emergency setting.

P – Past Pertinent History
Past medical history (PMH) can provide essential context for understanding the patient’s current presentation. This includes chronic conditions such as diabetes, hypertension, or asthma, as well as previous hospitalizations, surgeries, or significant illnesses. Understanding a patient’s medical history helps healthcare providers anticipate complications and tailor their approach. For instance, if a patient with a history of seizures presents with altered mental status, healthcare providers will prioritize ruling out or treating seizure activity or postictal states.

L – Last Oral Intake
Knowing the last oral intake—what the patient has eaten or drunk—can provide valuable information about the patient’s condition, especially in cases of poisoning, drug overdoses, or gastrointestinal distress. For example, the timing of food or drink ingestion could suggest an issue with digestion or absorption, which may influence the choice of interventions. In cases of poisoning, knowing whether the patient ingested a toxic substance recently can impact the decision to administer activated charcoal or other antidotes. Additionally, the last oral intake can be crucial if the patient is scheduled for surgery or other procedures, as it helps assess the risk of aspiration or anesthesia complications.

E – Events Leading to the Incident
Understanding the sequence of events that led to the current emergency is essential for diagnosing the cause and assessing the patient’s clinical needs. For example, was the patient involved in a motor vehicle accident, or did they experience a sudden onset of chest pain while exercising? Gathering this information helps to identify the mechanism of injury or the type of acute event, which could significantly alter the emergency management plan. It also provides insight into potential causes of the symptoms and any necessary preventive or therapeutic actions.

Purpose and Application of the SAMPLE Mnemonic in Rapid Triage

The SAMPLE mnemonic is a concise tool designed to quickly gather relevant historical information that can significantly impact clinical decision-making in the emergency department. This structured approach is particularly helpful in high-pressure environments where time is critical, such as during triage or when managing patients with complex or time-sensitive conditions.

The goal during history-gathering in an emergency is to obtain just enough, but not too much detail. Too much detail may delay treatment, while too little may result in missing critical information. For example, a lengthy review of a patient’s family history may be less pertinent in an acute situation compared to knowing their current medication list or the events leading to the emergency. The SAMPLE framework ensures that the provider gathers relevant information to make informed decisions about the next steps in care, whether that be immediate intervention, further diagnostics, or a more detailed secondary assessment.

The SAMPLE mnemonic is an effective tool for emergency practitioners to rapidly gather crucial information during triage and initial assessment. By focusing on the most important elements—signs and symptoms, allergies, medications, past medical history, last oral intake, and events leading up to the incident—providers can prioritize interventions, anticipate potential complications, and provide optimal care in emergency settings.

Performing a Focused Physical Exam

After performing a focused history, it is important to use the information gathered to guide your focused physical exam. For example, a patient presenting with the chief complaint of sore throat should receive an expedited examination of the head, ears, mouth, and neck. The rest of the physical exam should be deferred unless the patient has another complaint that is not covered by these sections. The purpose of the focused physical exam is to look for “red flag” exam findings that would warrant more immediate attention and intervention, such as the peritonitic abdomen in the patient presenting with abdominal pain, oropharyngeal swelling in the patient presenting with shortness of breath and rash, left-sided flaccidity in the patient presenting with sudden onset weakness and tingling, and other concerning findings [4].

Vital Signs and Objective Data

There are clues to key providers about how sick their patients are. One of the most important clues is a patient’s set of vitals; therefore, it is exceedingly important to obtain a full set of vitals for all patients arriving at the emergency department. Vitals at either extreme of the spectrum are equally important, and grossly abnormal vitals should prompt a more expedited triage and shorter waiting times. Other clues that help identify sick patients include the level of pain, duration of symptoms, level of consciousness, and mechanism of injury. Suppose someone is determined to be in distress at any point during the triage process. In that case, they must be brought to a designated patient care area for immediate ED provider attention. In the paragraphs below, we will discuss this further regarding adult populations.

a-photo-of-a-female-patient-in-the-emergency-department-triage (the image was produced by using ideogram 2.0)

Heart Rate

Bradycardia is a heart rate of less than 60 bpm, while tachycardia is a heart rate of more than 100 bpm [5]. If a patient is experiencing associated hypotension with an abnormal heart rate, then it is obvious that they are sick. However, there are other key questions that you may ask in the physical exam to elucidate further a patient’s severity of illness regarding an abnormal heart rate. For example, experiencing associated chest pain, palpitations, extreme fatigue or weakness, altered mental status, shortness of breath, or nausea can be signs that the abnormal heart rate is due to a concerning underlying pathology in the patient. Tachycardia can be indicative of infection, dysrhythmia, acute blood loss, and toxin exposure amongst other etiologies. It is also important to ask about medication use in these patients as this can be your first sign of an accidental (or intentional) chronotropic medication overdose – such as with beta-blockers, calcium channel blockers, and other medications that need to be seen by a medical provider quickly.

Blood Pressure

Hypotension is defined as a blood pressure less than 90/60 mmHg, while hypertension is defined as more than 140/90 mmHg [5]. With hypotension, it is important to first quickly assess if a patient is experiencing a decreased mental status and level of alertness in order to determine if any immediate interventions are needed – if so, this patient is definitely sick and cannot wait for care. Next, it is important to assess for possible causes of hypotension and severe illness, such as septic, hemorrhagic, neurogenic, and anaphylactic shock. For hypertension, it is important to assess for signs that could indicate end-organ failure, such as chest pain, shortness of breath, and focal neurologic deficits. Patients exhibiting the above symptoms should be evaluated sooner rather than later.

Respiratory Rate

Tachypnea is defined as a respiratory rate above 20 bpm, while bradypnea is defined as a respiratory rate below 12 bpm [5]. Apnea is the total absence of breathing. Bradypnea and apnea can be seen in many conditions, including traumatic brain injury and heroin overdose. Tachypnea is seen in many conditions, including asthma exacerbation and conditions causing metabolic derangement, such as diabetic ketoacidosis. If a patient is not breathing or experiencing decreased oxygen saturation along with abnormal respirations, then it is obvious they are sick. However, for those cases that are less obvious, it is important to observe the patient’s work of breathing with their respirations. Those who appear to have a significantly increased respiratory effort, are becoming tired, or are experiencing shallow respirations will need medical evaluation and care sooner rather than later. Their fatiguing respiratory effort will eventually lead to respiratory failure and hypoxia. Those with stories concerning an underlying process that could quickly compromise respiratory function should also be prioritized. For example, a patient who presents with a story suspicious of intracranial hemorrhage who appears sleepy and only moans in response to questions is at high risk for respiratory decompensation.

Oxygen Saturation

Hypoxia is defined as an oxygen saturation below 92% [5]. While different patients can tolerate various oxygen saturation levels depending on their smoking status, history of lung disease, and other past medical history, it is important to assess the work of breathing and level of alertness in patients with low readings. Patients who appear to have increased work of breathing, decreased respirations, or decreased level of alertness are at risk for respiratory decompensation. These patients should be evaluated and treated sooner rather than later.

Temperature

Hypothermia is defined as a temperature below 35 C. In contrast, hyperthermia is defined as a temperature above 38 C [5]. Hypothermic patients must be rewarmed depending on the degree of hypothermia (this will be discussed in later chapters). It is important to determine the reason for their hypothermia – such as sepsis, submersion injury, and prolonged cold exposure. There are many reasons for hyperthermia, including but not limited to infection, prolonged heat exposure, and certain types of medication overdose. The hyperthermic patient must be physically cooled and given antipyretics or other medications depending on the cause of their hyperthermia. These are all causes for concern and immediate interventions.

Pain

The severity and location of pain can also help identify patients who need prompt attention. Patients in severe pain will need immediate attention and medications to alleviate their pain. The location of pain can also be a clue to a patient’s severity of illness. For example, chest pain radiating to the back could represent an aortic dissection, right lower quadrant abdominal pain could represent appendicitis, and headache with neck stiffness could represent bacterial meningitis. Patients with concerning pain severity and location should be prioritized [6].

Duration and Mechanism

The duration of symptoms can also be a clue to a patient’s severity of illness. In general, acute complaints, or complaints that occur with a sudden or recent onset, should raise higher suspicion for serious etiologies than a chronic complaint that has been occurring without change for weeks to months [6]. A patient’s mechanism of injury is also important to consider; for example, a person who has fallen from a significant height or has been involved in a high-speed accident should be evaluated quickly as well.

Level of Consciousness

Level of consciousness exists on a spectrum, from those who are unresponsive to those who are completely awake and alert. Unresponsive patients should receive immediate attention and interventions, including chest compressions if they are without a pulse and intubation. Lethargic patients and those experiencing quickly decreasing levels of alertness should also be prioritized. Those sleepy or confused should be seen urgently, while those fully awake and alert may wait to be seen if they are without other concerning signs/symptoms [6].

Triage is a complex process involving several components, and it can be challenging. Triage providers play a crucial role in ensuring the efficiency and safety of the ED. They must quickly and accurately assess a patient’s severity of illness to determine how long different patients can safely wait for care. It is essential that they do not focus on diagnosing the patient’s condition during triage, as this can delay the process. Such delays can compromise care for all patients, allowing seriously ill individuals to go unnoticed for extended periods while their condition worsens. Remember that a comprehensive history, examination, diagnostic work-up, and treatment will occur once the patient is admitted to a care area.

Triage Systems

Triage is a complex process that needs to be done expediently, especially when facing large patient volumes. Fortunately, many triage systems have been developed to help guide providers in quickly and accurately risk-stratifying patients during the rapid triage assessment. We will discuss some of the most popular and widely used triage systems, such as the Manchester Triage System and the Emergency Severity Index.

Manchester Triage System

One of the most well-known and globally used triage systems is the Manchester Triage System (MTS). It was developed in the UK and is widely used worldwide. This triage system helps ensure patient safety by defining the maximum time each patient can wait before being seen and treated. The MTS contains flowcharts for various presenting complaints that help to distinguish the severity of illness based on key “discriminators” (signs and symptoms) [7]. Each level of severity is assigned a different color. Red indicates immediate evaluation, while blue indicates non-urgent evaluation (can wait up to 240 minutes). Flowcharts are available for various chief complaints in adult and pediatric patients. The MTS (Figure) for the adult chief complaint of “chest pain” is discussed below [8].

The Manchester Triage System

RED: Immediate/Life-Threatening

The red category signifies the highest level of urgency, where the situation is life-threatening and requires immediate medical intervention. The maximum waiting time is 0 minutes, indicating that the patient must receive attention without delay. Correlating examples for chest pain in this category include airway compromise, inadequate breathing, or shock. These conditions are critical as they can lead to rapid deterioration or death if not addressed promptly. Immediate treatment might involve airway management, advanced resuscitation, or stabilization of vital signs.

ORANGE: Emergent/Could Become Life-Threatening

The orange category represents conditions that are not immediately life-threatening but could escalate to critical levels if left untreated. The maximum waiting time in this category is 10 minutes, emphasizing the need for swift medical evaluation and intervention. Examples of chest pain scenarios in this category include severe pain, cardiac pain, acute shortness of breath, or abnormal pulse. These symptoms often indicate serious underlying issues such as myocardial infarction, severe arrhythmias, or pulmonary embolism, all of which require urgent diagnostic and therapeutic measures to prevent deterioration.

YELLOW: Urgent/Not Life-Threatening

In the yellow category, conditions are urgent but not immediately life-threatening. The maximum waiting time is 60 minutes, providing a moderate window for assessment and treatment. Correlating examples for chest pain include pleuritic pain, persistent vomiting, history of cardiac disease, or moderate pain. These symptoms may point to less severe causes, such as musculoskeletal issues, gastroesophageal reflux, or pleurisy. However, the history of cardiac disease suggests a need for careful evaluation to rule out more serious conditions.

GREEN: Semi-Urgent/Not Life-Threatening

The green category involves semi-urgent conditions where the likelihood of life-threatening complications is low. Patients in this category can wait up to 120 minutes for treatment. Examples include vomiting, mild pain, or recent problems. Chest pain in this category is typically associated with benign causes, such as anxiety, mild gastrointestinal issues, or a musculoskeletal strain. While these cases are not critical, timely assessment ensures patient comfort and prevents unnecessary progression of symptoms.

BLUE: Non-Urgent/Needs Treatment When Time Permits

The blue category is for non-urgent conditions that require treatment only when time permits. The maximum waiting time is 240 minutes, as these cases are unlikely to escalate to a critical level. Examples include other complaints that may not even directly relate to chest pain or are minor in nature. These could involve mild discomfort or non-specific symptoms that do not pose any immediate threat to the patient’s health. Such cases can be safely managed without priority over more urgent categories.

Emergency Severity Index

Much like the Manchester Triage System, the Emergency Severity Index triage system (developed in the USA) is also globally known and used. It stratifies patients into five levels: level 1, the most urgent, and level 5, the least urgent. It also helps to determine what resources are necessary to move a patient toward disposition. It is based on four key decision points: does the patient require life-saving interventions (Step A), are they in a high-risk situation (Step B), how many resources do they need (Step C), and what are their vitals (Step D)? The ESI Triage Algorithm, types of resources, and level of urgency, along with examples, are discussed below [9].

Step-by-Step ESI Triage Algorithm

  1. Step A: The first question asks whether the patient requires immediate, life-saving interventions. If the answer is “Yes,” the patient is classified as Level 1, indicating the highest level of urgency. If “No,” the triage proceeds to Step B.

  2. Step B: This step evaluates whether the patient is in a high-risk situation, is lethargic, confused, or in severe pain. A “Yes” response classifies the patient as Level 2, while a “No” response advances the process to Step C.

  3. Step C: At this stage, the need for medical resources is assessed. If the patient requires only one resource, they are categorized as Level 4. If multiple resources are needed, they may qualify for a higher urgency level, prompting a review in Step D.

  4. Step D: This step determines whether the patient exhibits “danger zone” vital signs, such as abnormal heart rate, respiratory rate, or oxygen saturation. A “Yes” response results in a Level 2 classification, while “No” leads to a Level 3 classification.

Types of Resources Defined by ESI

Resources play a critical role in the ESI system, as they help determine patient levels during Step C. Common resource types include:

  • Diagnostic Tools: Labs, EKG/ECG, X-rays, CT scans, MRI, or ultrasounds.
  • Treatment: IV fluids, IV/IM/nebulized medications, and specialist consultations.
  • Procedures: Simple procedures, such as laceration repair or Foley catheter insertion, are counted as one resource. Complex procedures, including conscious sedation, fracture reduction, and intubation, may require additional considerations.

Points according to required resources;

  • 1 point for Labs (e.g., blood tests), EKG/ECG or X-rays, or Advanced Imaging (e.g., CT, MRI, or ultrasound).
  • 1 point for IV fluids.
  • 1 point for IV, IM, or nebulized medications.
  • 1 point for a Specialist consultation.
  • 1 point for a Simple procedure, such as laceration repair or Foley catheter placement.
  • 2 points for a Complex procedure, such as conscious sedation, fracture reduction, or intubation.

These resource definitions allow triage staff to assess patient needs objectively. A higher number of resources often correlates with a more urgent ESI level.

ESI Levels and Their Corresponding Urgency

The ESI system categorizes patients into five levels of urgency based on their condition and resource needs:

  1. Level 1 (Immediate): Patients need immediate attention due to life-threatening conditions like cardiac arrest.
  2. Level 2 (Emergent): These patients are at high risk of rapid deterioration, such as those experiencing an asthma attack.
  3. Level 3 (Urgent, Multiple Resources): Patients with conditions requiring multiple resources, like abdominal pain, fall into this category.
  4. Level 4 (Stable, One Resource): These patients need only one resource, such as laceration repair.
  5. Level 5 (Stable, No Resources): Patients with stable conditions requiring no resources, such as a prescription refill, are classified here.

Advanced Triage

Once you are comfortable with the above basic triage concepts, you can familiarize yourself with advanced triage considerations, such as ordering an initial diagnostic work-up and treatments.

Ordering an Initial Diagnostic Work-Up and Other Orders

As soon as a patient is determined to be sick or unstable, your priority should be to place them in a patient care area as quickly as possible for medical attention. You can then place initial orders, which should be directed toward stabilizing them. Placing IVs early and facilitating early medication/fluid administration can be life-saving measures. Be sure to ask these patients (or their loved ones) early in their evaluation regarding their wishes for cardiopulmonary resuscitation (CPR) and intubation. Once a patient is stable, or if they’re already stable, you can use their pertinent history and physical exam findings to guide your initial diagnostic imaging and labs. Consider your most likely diagnoses and “can’t miss diagnoses” when placing these initial orders [10].

Author

Picture of Priya Arumuganathan

Priya Arumuganathan

Priya Arumuganathan, MD is a third year Emergency Medicine resident at West Virginia University. After residency, she will be completing a Global Emergency Medicine Fellowship at the University of Pennsylvania. During residency, Priya served as a Chief Resident and was very active in teaching core EM content, ultrasound skills, and procedural basics to medical students and new residents. Her rural background and training at several critical access hospitals have helped her build a foundation for working in low-resource environments, and she has been able to translate these skills to her global work. Her academic interests include EM education & training in low-resource environments, telemedicine, and rural health.

Picture of Scott Walker Findley

Scott Walker Findley

Dr. Findley is an associate professor with the WVU Department of Emergency Medicine. He splits time between the larger WVU academic centers and outlying rural emergency departments, spending most of his clinical time in single coverage facilities. After recognizing the challenges inherent in rural emergency medicine (EM), he designed and developed the WVU Division of Rural EM. Dr. Findley secured a federal telemedicine grant to expand telemedicine services in WV critical access hospitals, an institutional HOPE grant to assess per-birth needs in rural emergency departments, assisted with a rural specific response to COVID – 19, secured a position as medical director and advisor for Adventure WV, successfully launched a multisite rural EM rotation for residents, facilitated rural rotations for medical students, and oversaw the integration of rural EM lectures and simulated cases into the resident curriculum. In addition to remaining academically connected, Dr. Findley works closely with the WVU Emergency Department Divisions of ultrasound, EMS and Education to bring resources into the community sites and rural areas. Dr. Findley also sits on the national American College of Emergency Physicians (ACEP) Rural Emergency Medicine’s Task Force. He has taken an active role in research with local and national presentations as well as publishing in academic journals. Although these opportunities have been rewarding, Dr. Findley believes nothing teaches you more, maintains drive and sharpens focus better than pulling shifts and seeing patients and he plans to continue working the majority of his clinical hours in smaller departments.

Listen to the chapter

References

  1. Robertson-Steel I. Evolution of triage systems. Emerg Med J. 2006;23(2):154-155. doi:10.1136/emj.2005.030270
  2. Yancey CC, O’Rourke MC. Emergency Department Triage. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 31, 2022.
  3. West Virginia Office of Emergency Medical Services. (2016, January 1). Assessment Mnemonics. Appendix D. Retrieved April 23, 2023, from https://www.wvoems.org/files/protocols/appendix/appendix-d-assessment-mnemonics
  4. Society for Academic Emergency Medicine. (2008). Performing a complaint-directed history and Physical Examination. Clerkship Directors in Emergency Medicine. Retrieved April 23, 2023, from https://www.saem.org/about-saem/academies-interest-groups-affiliates2/cdem/for-students/online-education/m3-curriculum/group-focused-chief-complaint-history-physical-examination-and-differential-diagnosis/performing-a-complaint-directed-history-and-physical-examination
  5. Balakumaran, J. (2020, June 30). Interpreting critical vital signs. Medical Concepts. Retrieved April 23, 2023, from https://canadiem.org/interpreting-critical-vital-signs/
  6. Mackway-Jones, K., Marsden, J., & Windle, J. (2014). The Triage Method. In Emergency Triage (2nd ed., pp. 10–21). John Wiley & Sons.
  7. Cicolo, E. A., Ayache Nishi, F., Ciqueto Peres, H. H., & Cruz, D. A. (2017). Effectiveness of the Manchester Triage System on time to treatment in the emergency department: a systematic review protocol. JBI database of systematic reviews and implementation reports, 15(4), 889–898. https://doi.org/10.11124/JBISRIR-2016-003119
  8. Ganley, L., & Gloster, A. S. (2011). An overview of triage in the emergency department. Nursing standard (Royal College of Nursing (Great Britain) : 1987, 26(12), 49–58. https://doi.org/10.7748/ns2011.11.26.12.49.c8829
  9. Gilboy N, Tanabe T, Travers D, Rosenau AM. (2011). Emergency Severity Index (ESI): A Triage Tool for Emergency Department Care, Version 4. Implementation Handbook 2012 Edition. AHRQ Publication No. 12-0014. Rockville, MD. Agency for Healthcare Research and Quality.
  10. International Emergency Medicine Education Project. (2019, March 4). Core Senior EM Clerkship Topics. Emergency Medicine Clerkship – Approach to Chief Complaints. Retrieved April 23, 2023, from https://iem-student.org/em-clerkship-topics/

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Antidotes (2024)

~ iEM Education Project Team ~ Leave a comment

by Sarah Alzaabi

Authors
Listen

Introduction

An antidote is a specific agent designed to counteract the toxic effects caused by drugs or poisons [1]. These substances play a crucial role in toxicology, as they can effectively mitigate or reverse the harmful consequences of various toxic exposures. In clinical practice, the availability of antidotes is somewhat limited, with only a select number approved for use depending on the type of toxin involved [2].

It’s important to note that antidotes are not administered indiscriminately; instead, they are used based on clearly defined clinical guidelines. Each antidote has specific indications that dictate when it should be given, ensuring that patients receive the appropriate treatment in situations of toxicity. Proper identification of the toxin and the clinical scenario is essential to determine the need for an antidote and to maximize its therapeutic efficacy.

Many poisons have no true antidote, and the poison(s) involved may initially be unknown [3, 4]. Furthermore, limiting the differential diagnosis to poisoning can deter the identification of other pathologies that may exist in these patients [3, 4]. Therefore, the initial approach should be to assess and stabilize [4, 5] thoroughly. Similar to any compromised patient, the attention is directed toward securing the airway, breathing, circulation, and decontamination [4, 5]. There are only a few indications where antidotes are prioritized over cardiopulmonary stabilization, i.e., naloxone for opioid toxicity, cyanide antidotes for cyanide toxicity, and atropine for organophosphate poisoning [5]. Otherwise, most patients will have good outcomes with supportive management and a period of observation [1, 3, 4, 5].

Administration of pharmacologic antagonists may worsen the outcome in some situations and is not recommended [2, 3]. Therefore, the physician should know the indications and contraindications of each antidote [2, 3]. When in doubt, consult a poison control center or a medical or clinical toxicologist [2, 4].
In summary, it’s important to understand that antidotes should be utilized as complementary treatments rather than the sole focus in managing poisoning cases [1]. The primary objective should always be to address the patient’s overall condition, taking into account their symptoms and needs, rather than concentrating exclusively on the specific toxin involved [4]. This approach ensures a more comprehensive and effective care strategy for individuals affected by poisoning.

Pregnant Patients and Antidotes

Limited data is available on the use of antidotes in pregnancy [4]. Hence, the teratogenic potential of antidotes is not fully understood [7]. The general initial management principles are the same, and stabilization of the mother is the priority [6].

The risks and benefits of using or withholding antidotes must be assessed. In general, antidotes are not used for uncertain indications, but proven effective treatments should not be withheld from the mother based on theoretical danger to the fetus [4].

There is no known indication for fetal antidote therapy [7]. However, if an antidote is to be given for fetal benefit, it should be done rapidly in the acute setting [7]. This specifically applies to chelators such as dimercaprol, calcium EDTA, and deferoxamine, which will prevent the toxin from passing into fetal circulation [7].

The following section presents information about various antidotes, organized in alphabetical order.

Antidotes

Atropine

General Information

  • Anticholinergic agent, competitive muscarinic antagonist [3, 4, 5, 8].

Indications

  • Organophosphate poisoning, carbamates, nerve agents [3, 4, 5, 8].

Precautions

  • Excessive doses may cause anticholinergic symptoms [5].

Dose/Administration

  • Adults: Start with 1-2 mg IV, double the dose every 2-3 minutes to reach the goal [3, 4, 5, 8].
  • Children: 0.02 mg/kg IV (minimum of 0.1 mg) [3].

Other Notes

  • Large doses may be required.
  • Goal: Drying of respiratory secretions/improved work of breathing [3, 8].
  • Tachycardia is not the endpoint (atropine helps with muscarinic effects; pralidoxime is used for nicotinic effects) [3, 8].

Calcium

General Information

  • Calcium chloride 10% (1 g/10 mL, 27.2 mg/mL elemental Ca).
  • Calcium gluconate 10% (9 mg/mL elemental Ca), one-third strength of calcium chloride [5].

Indications

  • Calcium channel blocker toxicity, hydrofluoric acid exposure, hyperkalemia, hypermagnesemia [4, 5, 9].

Precautions

  • Calcium chloride extravasation can cause soft tissue necrosis; prefer central line administration [9].
  • Continuous monitoring is recommended [9].

Dose/Administration

  • Adults:
    • Calcium chloride: 0.5-1 g IV (5-10 mL) [5, 9].
    • Calcium gluconate: 1-3 g IV (10-30 mL) [5].
  • Children: 0.15 mL/kg calcium chloride IV [5].
  • IV bolus over 5-10 minutes; repeated doses every 10-20 minutes as needed, guided by serum Ca+ or QT interval [9].
  • Infusion available [9].

Other Notes

  • For HF acid skin burns: Topical 2.5% calcium gel or local injection of calcium gluconate [9].
  • Regional block with intra-arterial or IV calcium gluconate for extremity exposure [9].
  • Nebulized calcium gluconate for HF acid inhalation injury [9].

Cyproheptadine

General Information

  • Antihistaminic and antiserotonergic agent; also has anticholinergic activity [10].

Indications

  • Serotonin syndrome [4, 10].

Dose/Administration

  • Adults: 8 mg every 8 hours for 24 hours (if response observed) [10].
  • Children: 4 mg (not well established) [10].

Deferoxamine

General Information

  • Iron-chelating agent that converts iron to a water-soluble complex for renal clearance [3, 11].

Indications

  • Systemic iron toxicity (e.g., severe gastroenteritis, shock, metabolic acidosis, altered mental status) [3, 4, 11].
  • Iron levels >500 µg/dL or multiple pills on radiography [3, 4, 11].
  • Chronic iron overload [3, 4, 11].

Precautions

  • Hypotension may occur at rapid infusion rates; ensure adequate hydration [3].
  • Cardiac monitoring is needed [11].

Dose/Administration

  • Start with IV infusion: 15 mg/kg/h (maximum 1 g/h) over 6 hours; re-evaluate [3, 11].
  • Infusion rate can be increased in critical patients if blood pressure allows [11].

Other Notes

  • Urine may become rusty-red as iron is excreted [3, 11].

Digoxin Immune Fab

General Information

  • Fab fragments of antibodies to digoxin, reversing cardiotoxic effects [1, 3].

Indications

  • Digoxin overdose with potassium >5 mEq/L after acute ingestion, hemodynamic instability, or life-threatening dysrhythmias [3].
  • Poisoning by other cardiac glycosides (e.g., Oleander) [1, 3, 5, 12].

Precautions

  • Close monitoring of digoxin serum levels, vital signs, and ECG. Resuscitation equipment should be ready [12].

Dose/Administration

  • Acute overdose:
    • Stable patients: 5 vials.
    • Unstable patients: 10-20 vials [3, 5].
  • Chronic overdose: Start with 1-2 vials, repeat after 60 minutes if needed [12].
  • Calculate dose if the ingested dose is known (40 mg Fab binds 0.6 mg digoxin) [3, 5].
  • Bolus in life-threatening conditions (e.g., cardiac arrest) or infusion over 30 minutes, monitoring clinical response [3, 12].

Other Notes

  • For other cardiac glycoside poisoning: Start with 5 vials [3, 12].

Dimercaprol (BAL)

General Information

  • Heavy metal chelator [1, 14].

Indications

  • Severe lead, inorganic arsenic, and mercury poisoning [1, 4, 13].

Precautions

  • Severe adverse effects include nephrotoxicity; consider using EDTA or succimer instead if possible [13].

Dose/Administration

  • 3 mg/kg IM every 4 hours for 48 hours, then every 12 hours for 7-10 days based on clinical response [13].

Ethanol

General Information

  • Blocks formation of toxic metabolites of alcohols [14].

Indications

  • Methanol and ethylene glycol poisoning (second-line to fomepizole) [5, 14].

Precautions

  • Maintain blood ethanol concentration between 100-150 mg/dL [14].

Dose/Administration

  • IV:
    • Loading: 10 mL/kg of 10% ethanol.
    • Maintenance: 1-2 mL/kg/h of 10% ethanol [14].
  • Oral:
    • Loading: 1.8 mL/kg of 43% ethanol.
    • Maintenance: 0.2-0.4 mL/kg/hour of 43% ethanol [14].

Flumazenil

General Information

  • Competitive antagonist of GABA-benzodiazepine receptors [1, 2, 3, 15].

Indications

  • Benzodiazepine overdose (limited role), reversal of procedural sedation, accidental pediatric ingestion [1, 3, 5, 15].

Precautions

  • May cause withdrawal or seizures, especially in benzodiazepine dependence or mixed overdoses [2, 3, 15].

Dose/Administration

  • Adults: 0.2 mg IV over 30 seconds, repeat every minute until reversal (maximum 3 mg) [1, 3, 5, 15].
  • Children: 0.01-0.02 mg/kg, repeat every minute [1, 5, 15].

Other Notes

  • Limited role due to risk of seizures [1, 3, 15].

Fomepizole

General Information

  • Alcohol dehydrogenase inhibitor [1, 3, 16].

Indications

  • Methanol and ethylene glycol toxicity (first-line due to better side effect profile) [1, 3, 5, 16].

Dose/Administration

  • Loading dose: 15 mg/kg IV infusion in 100 mL normal saline or 5% dextrose over 30 minutes [1, 3, 16].
  • Maintenance dose: 10 mg/kg every 12 hours for 48 hours, then 15 mg/kg every 12 hours until alcohol concentrations <20 mg/dL [1, 16].
  • In dialyzed patients: Give every 4 hours or continuous infusion of 1 mg/kg/h [16].

Other Notes

  • Continue therapy until alcohol concentrations are <20 mg/dL and the patient is asymptomatic [3].

Glucagon

General Information

  • Increases cyclic AMP (cAMP).
  • Positive inotropic and chronotropic properties, similar to beta-agonists [18].

Indications

  • β-blocker toxicity (adjunct).
  • Calcium channel blocker toxicity [5, 17, 18].

Precautions

  • Induces vomiting; consider anti-emetics and airway management [18, 19].

Dose/Administration

  • Adults: 5-10 mg IV bolus over 1-2 minutes [5, 18, 19].
  • Children: 0.05-0.1 mg/kg IV [19].

Other Notes

  • If there is a clinical response, start an infusion [18].
  • Intravenous fluids, vasopressors, and high-dose insulin with dextrose are first-line treatments for β-blocker toxicity [19].

Hydroxocobalamin

General Information

  • Precursor of Vitamin B12 [20].

Indications

  • Cyanide toxicity (forms cyanocobalamin by displacing hydroxyl group) [3, 5, 20].

Precautions

  • Safe drug with low side effects.

Dose/Administration

  • Adults: 5 g in 100 mL normal saline IV infusion over 15 minutes; repeat if needed [3, 5, 20].
  • Children: 70 mg/kg IV over 15 minutes (maximum 5 g) [3, 5].

Other Notes

  • Causes orange-red discoloration of skin and urine, resolving within 24-48 hours [3].

Insulin (High Dose)

General Information

  • Strong inotropic effects [21].

Indications

  • Calcium channel blocker and β-blocker toxicity [5, 21].

Precautions

  • Monitor for hypoglycemia, hypokalemia, hypomagnesemia, and hypophosphatemia [21].

Dose/Administration

  • Adults:
    • Glucose 25 g (50 mL of dextrose 50%) IV bolus → 1 IU/kg IV bolus of short-acting insulin → 25 g/h glucose and 0.5-1 IU/kg/h short-acting insulin infusion [21].
  • Titrate glucose to maintain levels between 6-8 mmol/L [21].

Intravenous Lipid Emulsion

General Information

  • 20% lipid emulsion as a parenteral nutrient.
  • Expands the lipid compartment within the intravascular space, sequestering lipid-soluble drugs from tissues [1, 5].

Indications

  • Overdose by drugs with high protein binding and large volume of distribution, e.g., local anesthetics (bupivacaine), β-blockers, and calcium channel blockers [1, 5].

Dose/Administration

  • Adults: 100 mL IV bolus over 1 minute (repeat every 5 minutes, maximum 2 doses) → 18 mL/min IV infusion for 20 minutes [5].
  • Children: 1.5 mL/kg IV bolus over 1 minute (repeat every 5 minutes, maximum 2 doses) → 0.25 mL/kg/min IV infusion for 20 minutes [5].

Methylene Blue

General Information

  • Reduces methemoglobin (MetHb) to hemoglobin [5, 22].

Indications

  • Symptomatic methemoglobinemia.
  • MetHb levels >20% in asymptomatic patients.
  • Oxidizing toxins (e.g., nitrites, benzocaine, sulfonamides) [5, 22].

Precautions

  • Pulse oximetry is unreliable in methemoglobinemia.
  • May cause hemolysis in G6PD deficiency [3, 22].

Dose/Administration

  • 1-2 mg/kg slow IV injection over 5 minutes; may repeat after 30-60 minutes [5, 22].

Other Notes

  • Monitor MetHb levels frequently until a consistent decrease is observed [22].

N-acetylcysteine (NAC)

General Information

  • Prevents hepatocellular injury by restoring glutathione stores, which conjugate the toxic metabolite NAPQI [1, 3, 23].

Indications

  • Serum acetaminophen levels above toxic threshold (>4 hours after ingestion).
  • Single ingestion >150 mg/kg.
  • Evidence of liver injury [1, 3, 4, 23].

Dose/Administration

  • Oral: 140 mg/kg loading dose → 70 mg/kg every 4 hours for 17 doses [1, 3, 23].
  • IV: 150 mg/kg in 200 mL of 5% dextrose over 60 minutes → 50 mg/kg diluted in 500 mL of 5% dextrose over 4 hours → 100 mg/kg diluted in 1000 mL of 5% dextrose over 16 hours [1, 3, 23].

Other Notes

  • Oral therapy may not be well tolerated due to taste and odor [23].

Naloxone

General Information

  • Opioid antagonist, diagnostic, and therapeutic agent [1, 2, 3].

Indications

  • Opioid toxicity with respiratory and CNS depression [1, 2, 3, 5].

Precautions

  • Re-sedation may occur due to naloxone’s short half-life; monitor for at least 4 hours.
  • Withdrawal in chronic/opioid-dependent users [1, 2, 3].

Dose/Administration

  • Adults: 0.4-2 mg IV; repeat every 2-3 minutes up to a maximum of 10 mg [1, 2, 3].
  • Children: 0.01 mg/kg IV [1, 3].

Other Notes

  • Goal: Adequate respiratory rate, normal oxygen saturation on room air, improved level of consciousness [3, 5].
  • Miosis is an unreliable indicator [5].

Octreotide

General Information

  • Synthetic analogue of somatostatin [24].

Indications

  • Hypoglycemia secondary to sulfonylurea [24].

Precautions

  • Breakthrough hypoglycemia may occur [24].

Dose/Administration

  • Adults:
    • 50 µg IV bolus → 25 µg/h infusion.
    • Alternatively, 100 µg IM or SC every 6 hours [24].
  • Children: 1 µg/kg IV bolus or SC → 1 µg/kg/h IV infusion [24].

Other Notes

  • Euglycemia needs to be maintained for 12 hours off the infusion before the patient is medically cleared [24].

Physostigmine

General Information

  • Reversible acetylcholinesterase inhibitor [25].

Indications

  • Neurological anticholinergic symptoms, e.g., delirium and seizures (crosses the blood-brain barrier) [5, 25].

Precautions

  • Contraindicated in bradycardia, AV block, and bronchospasm [25].

Dose/Administration

  • Adults: 0.5-1 mg slow IV push over 5 minutes; repeat in 10-30 minutes if needed [25].
  • Children: 0.02 mg/kg IV (maximum dose of 0.5 mg) [25].

Other Notes

  • Confirm absence of conduction defects on a 12-lead ECG before administration.
  • Rapid administration may cause a cholinergic crisis; treat with atropine if this occurs [25].

Pralidoxime

General Information

  • Reactivates acetylcholinesterase inhibition [1, 3, 26].

Indications

  • Early organophosphate poisoning (<2 hours).
  • Nerve agents [1, 3, 5, 26].

Precautions

  • Rapid administration can cause laryngospasm, muscle rigidity, and transient respiratory impairment [3].

Dose/Administration

  • Adults: 1-2 g IV in 100 mL of 0.9% saline over 15-30 minutes → 500 mg/h IV infusion [3, 26].
  • Children: 25-50 mg/kg → 10-20 mg/kg/h infusion [3, 26].

Other Notes

  • Administer in the early phase before irreversible acetylcholinesterase binding occurs.
  • Adequate atropine doses should be given concurrently [1, 3, 26].

Pyridoxine (Vitamin B6)

General Information

  • Vitamin B6, essential for GABA production [3, 27].

Indications

  • Isoniazid, hydrazine, and Gyromitra poisoning.
  • Ethylene glycol poisoning (adjunct therapy) [3, 5, 27].

Dose/Administration

  • Adults:
    • For isoniazid poisoning: 1 g per gram of ingested isoniazid, given as 0.5 g/min infusion until seizures stop. If unknown, give 5 g IV empirically [3, 5, 27].
  • Children: 70 mg/kg IV, maximum 5 g [5, 27].

Other Notes

  • For ethylene glycol toxicity: 50 mg IV every 6 hours [27].

Sodium Bicarbonate

General Information

  • Hyperosmolar sodium bicarbonate injection [28].

Indications

  • Cardiotoxicity due to fast sodium channel blockade presenting as QRS widening and ventricular dysrhythmias (e.g., TCA poisoning).
  • Urine alkalinization [2, 5, 28].

Precautions

  • Monitor for hypokalemia and hypernatremia.
  • Maintain serum pH between 7.50-7.55 [28].

Dose/Administration

  • Start with 1-2 mEq/kg IV over 1-2 minutes → 0.3 mEq/kg per hour IV infusion if needed [5].
  • Repeated doses may require intubation and hyperventilation to maintain pH >7.5-7.55 [28].

Sodium Calcium Edetate (EDTA)

General Information

  • IV heavy metal chelator [29].

Indications

  • Severe lead toxicity with lead levels >70 µg/dL [29].

Precautions

  • Risk of nephrotoxicity, ECG changes, and transaminitis.
  • Hospital admission required [29].

Dose/Administration

  • Dilute 25-50 mg/kg in 500 mL of 0.9% saline or 5% dextrose; infuse over 24 hours, starting 4 hours after the first dose of dimercaprol [29].
  • In encephalopathy, continuous infusion for 5 days until stabilization [29].

Other Notes

  • Once clinically improved, switch to oral succimer if tolerated [29].

Sodium Thiosulfate

General Information

  • Assists the body in detoxifying cyanide [1, 30].

Indications

  • Cyanide poisoning [1, 5, 30].

Precautions

  • In severe cases, use with other antidotes (e.g., hydroxocobalamin) [30].

Dose/Administration

  • Adults: 50 mL of 25% solution (12.5 g; 1 ampoule) IV over 10 minutes [1, 5, 30].
  • Children: 1.65 mL/kg IV; repeat after 30 minutes if clinically indicated [30].

Succimer (DMSA)

General Information

  • Oral heavy metal chelator [31].

Indications

  • Symptomatic lead poisoning.
  • Asymptomatic lead poisoning with lead levels >60 µg/dL in adults or >45 µg/dL in children [5, 31].

Precautions

  • Reversible neutropenia, gastrointestinal upset, and liver function abnormalities [31].

Dose/Administration

  • 10 mg/kg three times a day for 1 week → two times a day for 2 weeks [31].

Other Notes

  • Monitor serum lead levels during treatment [31].

Antidotes play a crucial role in managing toxicological emergencies in the emergency department. While their use is often specific and limited, they provide life-saving interventions in cases of confirmed poisonings such as opioid overdoses, cyanide poisoning, or organophosphate exposure. However, their administration requires careful assessment of indications, contraindications, and potential adverse effects. Emergency clinicians must prioritize stabilizing airway, breathing, and circulation before considering antidote administration, except in scenarios where antidotes are critical to immediate survival. The decision to use an antidote should be guided by clinical judgment, toxicology consultation, and evidence-based guidelines. Ultimately, antidotes should be viewed as adjunctive therapies, emphasizing the principle of treating the patient comprehensively rather than focusing solely on the poison.

Author

Picture of Sarah Alzaabi

Sarah Alzaabi

Sarah Alzaabi, MD is a graduate from the United Arab Emirates University. She is currently a medical intern at Sheikh Shakhbout Medical City, Abu Dhabi, with a longstanding interest in Emergency Medicine. She is a big advocate for the FOAMed movement; and is proud to be a part of the fantastic team at iEM. She is excited to develop innovative ways to provide accessible education for anyone in need. Sarah has a particular interest in lifestyle and nutrition and spends time learning about how to educate others about succeeding in medicine while maintaining a healthy lifestyle.

Listen to the chapter

References

  1. Chacko B, Peter JV. Antidotes in Poisoning. Indian J Crit Care Med. 2019;23(Suppl 4):S241-S249. doi:10.5005/jp-journals-10071-23310
  2. Erickson TB, Thompson TM, Lu JJ. The Approach to the Patient with an Unknown Overdose. Emerg Med Clin N Am. 2007;25(2):249-81.
  3. Holstege CP, Dobmeier SG, Bechtel LK. Critical care toxicology. Emerg Med Clin North Am. 2008;26(3):715-39.
  4. Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. Principles of Managing the Acutely Poisoned or Overdosed Patient. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw Hill; 2019. Accessed March 04, 2023. https://accessemergencymedicine-mhmedical-com.uaeu.idm.oclc.org/content.aspx?bookid=2569&sectionid=210267250
  5. Greene S. General Management of Poisoned Patients. Tintinalli’s Emergency Medicine. 8 ed: MC Graw Hill; 2014. p. 1207.
  6. Gei AF, Suarez VR. Poisoning in Pregnancy. In: Foley MR, Strong, Jr TH, Garite TJ. eds. Obstetric Intensive Care Manual, 5e. McGraw Hill; . Accessed March 04, 2023. https://obgyn-mhmedical-com.uaeu.idm.oclc.org/content.aspx?bookid=2379&sectionid=185993887
  7. Bailey, B. (2003), Are there teratogenic risks associated with antidotes used in the acute management of poisoned pregnant women?. Birth Defects Research Part A: Clinical and Molecular Teratology, 67: 133-140. https://doi-org.uaeu.idm.oclc.org/10.1002/bdra.10007
  8. Long N. Atropine. Life in the Fast Lane. https://litfl.com/atropine/. Published November 3, 2020. Accessed March 23, 2023.
  9. Long N. Calcium. Life in the Fast Lane. https://litfl.com/calcium/. Published November 3, 2020. Accessed March 23, 2023.
  10. Long N. Cyproheptadine. Life in the Fast Lane. https://litfl.com/cyproheptadine/. Published November 3, 2020. Accessed March 23, 2023.
  11. Long N. Desferrioxamine. Life in the Fast Lane. https://litfl.com/desferrioxamine/. Published November 3, 2020. Accessed March 23, 2023.
  12. Long N. Digoxine Immune Fab. Life in the Fast Lane. https://litfl.com/digoxin-immune-fab/. Published November 3, 2020. Accessed March 23, 2023.
  13. Long N. Dimercarpol. Life in the Fast Lane. https://litfl.com/dimercaprol/. Published November 3, 2020. Accessed March 23, 2023.
  14. Long N. Ethanol. Life in the Fast Lane. https://litfl.com/ethanol/. Published November 3, 2020. Accessed March 23, 2023.
  15. Long N. Flumazenil. Life in the Fast Lane. https://litfl.com/flumazenil/. Published November 3, 2020. Accessed March 23, 2023.
  16. Long N. Fomepizole. Life in the Fast Lane. https://litfl.com/fomepizole/#:~:text=Fomepizole%20is%20an%20alcohol%20dehydrogenase,methanol%20and%20ethylene%20glycol%20poisoning. Published June 15, 2021. Accessed March 23, 2023.
  17. Long N. Glucagon. Life in the Fast Lane. https://litfl.com/glucagon/. Published November 3, 2020. Accessed March 24, 2023.
  18. Nickson C. Glucagon Therapy. Life in the Fast Lane. https://litfl.com/glucagon-therapy/. Published November 3, 2020. Accessed March 24, 2023.
  19. Atlantic Canada Poison Centre. https://atlanticcanadapoisoncentre.ca/glucagon-pediatric.html. Published March 2017. Accessed March 30, 2023.
  20. Long N. Hydroxocobalamin. Life in the Fast Lane. https://litfl.com/hydroxocobalamin/. Published November 3, 2020. Accessed March 24, 2023.
  21. Long N. Insulin (High dose). Life in the Fast Lane. https://litfl.com/insulin-high-dose/. Published November 3, 2020. Accessed March 24, 2023.
  22. Long N. Methylene Blue. Life in the Fast Lane. https://litfl.com/methylene-blue/. Published November 3, 2020. Accessed March 24, 2023.
  23. Long N. N-acetylcysteine. Life in the Fast Lane. https://litfl.com/n-acetylcysteine/#:~:text=Acetylcysteine%20is%20the%20most%20widely,of%20NAPQI%20(toxic%20paracetamol%20metabolite. Published November 3, 2020. Accessed March 24, 2023.
  24. Long N. Octreotide. Life in the Fast Lane. https://litfl.com/octreotide/. Published November 3, 2020. Accessed March 24, 2023.
  25. Long N. Physostigmine. Life in the Fast Lane. https://litfl.com/physostigmine/. Published November 3, 2020. Accessed March 24, 2023.
  26. Long N. Pralidoxime. Life in the Fast Lane. https://litfl.com/pralidoxime/#:~:text=This%20is%20the%20oxime%20commonly,and%20the%20OP%2FCarbamate%20involved. Published November 3, 2020. Accessed March 24, 2023.
  27. Long N. Pyridoxine. Life in the Fast Lane. https://litfl.com/pyridoxine/. Published November 3, 2020. Accessed March 24, 2023.
  28. Long N. Sodium Bicarbonate. Life in the Fast Lane. https://litfl.com/sodium-bicarbonate/. Published November 27, 2022. Accessed March 24, 2023.
  29. Long N. Sodium Calcium edetate. Life in the Fast Lane. https://litfl.com/sodium-calcium-edetate/#:~:text=Sodium%20Calcium%20Edetate%20(EDTA)%20is,3.38%20micro%20mol%2FL). Published November 3, 2020. Accessed March 24, 2023.
  30. Long N. Sodium thiosulphate. Life in the Fast Lane. https://litfl.com/sodium-thiosul phate/#:~:text=Sodium%20thiosulfate%20enhances%20the%20endogenous,hydroxocobalamin%20in%20severe%20cyanide%20toxicity.Published November 3, 2020. Accessed March 24, 2023.
  31. Long N. Succimer. Life in the Fast Lane. https://litfl.com/succimer/#:~:text=Succimer%20(DMSA)%20is%20an%20orally,2.9%20micro%20mol%2FL). Published November 3, 2020. Accessed March 24, 2023.

Reviewed and Edited By

Picture of Arif Alper Cevik, MD, FEMAT, FIFEM

Arif Alper Cevik, MD, FEMAT, FIFEM

Prof Cevik is an Emergency Medicine academician at United Arab Emirates University, interested in international emergency medicine, emergency medicine education, medical education, point of care ultrasound and trauma. He is the founder and director of the International Emergency Medicine Education Project – iem-student.org, chair of the International Federation for Emergency Medicine (IFEM) core curriculum and education committee and board member of the Asian Society for Emergency Medicine and Emirati Board of Emergency Medicine.

Push Th(d)ose Vasopressors

Push Th(d)ose Vasopressors
~ Neha Hudlikar, UAE ~ Leave a comment

Background

Since Scott Weingart first advocated for using push-dose pressors in the Emergency Department (ED) over a decade ago(1), push-dose vasopressors, also known as bolus-dose vasopressors have seemingly found their way into many EDs. However, recent studies have sought to ask more questions regarding its use and safety in the Emergency Department.

Vasopressors such as epinephrine and norepinephrine are commonly used for regulating and maintaining adequate blood pressure or mean arterial pressure (MAP). While these are usually administered as a continuous infusion via central access, administering them as a small bolus through peripheral access came to be known as push-dose vasopressor in practice.

Traditionally, this small bolus strategy was used in the operating room (OR) by anesthetists to treat transient hypotension due to sedating agents or spinal anesthesia. Multiple studies have supported the safety and efficacy of push-dose vasopressors in this clinical setting/patient population (2).

Swensen, et al. (3) studied the safety of bolus-dose phenylephrine for hypotension in the Emergency Department, however, data on the efficacy and safety of push-dose pressors remains sparse in ED and in-patient settings. Studies published in the past few years have questioned the lack of evidence regarding the safety and efficacy of push-dose pressor use in ED settings and highlighted some negative consequences of its use (4). To understand the concerns, it’s important we first understand the vasopressors, indications for use, and preparation in the ED.

Push-dose pressors in the Emergency Department

The two common vasopressors used as push-dose pressors in the Emergency Department are Epinephrine and Phenylephrine. Patients needing emergency airway, traumatic brain injury, and post-cardiac arrest with the return of spontaneous circulation may all experience hypotension which could lead to adverse outcomes. Push-does pressors have been proposed as a temporary measure to limit the hypotension while a vasopressor infusion/definitive treatment is being set up (5).

phenilephrine vs epinephrine
push dose epinephrine
push dose phenilephrine

Clinical settings in the ED where the use of push-dose pressor is proposed:

  1. Airway management: Hypotension prior, during, and post-intubation could be treated with bolus-dose vasopressors. Panchal et al. (6) did a retrospective chart review of intubated hypotensive patients in which phenylephrine was used. Bolus-dose phenylephrine demonstrated an increase in systolic blood pressure and the authors recommended further studies to understand the best use of phenylephrine for post-intubation hypotension.
  2. Return of spontaneous circulation (ROSC): In patients with ROSC, bolus-dose pressors may aid in the maintenance of end-organ perfusion, which is often impaired after ROSC (7).
  3. Traumatic brain injury: By rapidly increasing mean arterial pressure and thus cerebral perfusion pressure, bolus-dose vasopressors may help to prevent secondary brain injury.

What are the concerns regarding the use of push-dose pressors in the ED?

Acquisto and Bodkin (8) cited a few dosing errors while using push-dose pressors and highlighted that emergency physicians are less familiar with the practice of medication preparation/manipulation and hence dosing errors are expected, inadvertently causing patients more harm than benefit. They also emphasized on the lack of evidence in the literature regarding the efficacy and safety of push-dose pressors in a stressful environment like the ED.

Rotando and Picard et al. (9) in their prospective observational study of 146 patients receiving push-dose pressors in the ICU had thirteen (11.2%) patients have a dose-related medication error and seventeen (11.6%) adverse events. They concluded while push-dose pressors where efficacious, they were associated with adverse drug events and medication errors.

Cole et al (10). performed a retrospective analysis of 249 patients receiving push-dose pressors and found a higher incidence of adverse hemodynamic effects (39%) and human errors (19%). They emphasized the need for further studies to question whether push-dose pressors improve outcomes, and if so, how to safely implement them in practice.

Another concern raised is whether physicians may bypass standard resuscitation practices of fluid boluses in favor of using push-dose pressors. Schwartz et al. (11) found that only 34% of patients received an appropriate fluid challenge before using push-dose pressors in a retrospective chart review of 73 patients receiving push-dose pressors for acute hypotension in the ED. Furthermore, it appeared that patients who did not receive an appropriate fluid bolus needed more doses of bolus-dose pressors followed by the need for continuous vasopressor infusion within 30 minutes of bolus-dose pressor use.

Emergency physicians work in stressful environments which raises concerns on the ability of the physician to perform accurate dose calculations under duress (4). The prepared syringe also contains multiple individual doses, and using more concentrated solutions potentially increases the risk of overdose and extravasation injury (12).

Conclusion

While the practice of using push-dose pressors has found its way into the Emergency Department, it is crucial to acknowledge that evidence regarding its safety and benefits is limited. However, rather than disregarding the practice, high-quality research should be encouraged, which could potentially be practice-changing. Holden et al. (12) offer a framework of operational and safety considerations for the use of push-dose pressors in the ED and is a must-read for all using push-dose pressors in their current practice.

References

  1. Scott Weingart. EMCrit Podcast 6 – Push-Dose Pressors. EMCrit Blog. Published on July 10, 2009. Accessed on September 25th 2020. Available at [https://emcrit.org/emcrit/bolus-dose-pressors/ ].
  2. Lee A, Ngan Kee WD, Gin T. A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery. Anesth Analg. 2002 Apr;94(4):920-6, table of contents. doi: 10.1097/00000539-200204000-00028. PMID: 11916798.
  3. Swenson K, Rankin S, Daconti L, Villarreal T, Langsjoen J, Braude D. Safety of bolus-dose phenylephrine for hypotensive emergency department patients. Am J Emerg Med. 2018 Oct;36(10):1802-1806. doi: 10.1016/j.ajem.2018.01.095. Epub 2018 Feb 19. PMID: 29472039.
  4. Cole JB. Bolus-Dose Vasopressors in the Emergency Department: First, Do No Harm; Second, More Evidence Is Needed. Ann Emerg Med. 2018 Jan;71(1):93-95. doi: 10.1016/j.annemergmed.2017.05.039. Epub 2017 Jul 26. PMID: 28754354.
  5. Weingart S. Push-dose pressors for immediate blood pressure control. Clin Exp Emerg Med. 2015;2(2):131-132. Published 2015 Jun 30. doi:10.15441/ceem.15.010
  6. Panchal AR, Satyanarayan A, Bahadir JD, Hays D, Mosier J. Efficacy of Bolus-dose Phenylephrine for Peri-intubation Hypotension. J Emerg Med. 2015 Oct;49(4):488-94. doi: 10.1016/j.jemermed.2015.04.033. Epub 2015 Jun 20. PMID: 26104846.
  7. Gottlieb M. Bolus dose of epinephrine for refractory post-arrest hypotension. CJEM. 2018 Oct;20(S2):S9-S13. doi: 10.1017/cem.2016.409. Epub 2017 Jan 10. PMID: 28069098.
  8. Acquisto NM, Bodkin RP, Johnstone C. Medication errors with push dose pressors in the emergency department and intensive care units. Am J Emerg Med. 2017 Dec;35(12):1964-1965. doi: 10.1016/j.ajem.2017.06.013. Epub 2017 Jun 7. PMID: 28625533.
  9. Rotando A, Picard L, Delibert S, Chase K, Jones CMC, Acquisto NM. Push dose pressors: Experience in critically ill patients outside of the operating room. Am J Emerg Med. 2019 Mar;37(3):494-498. doi: 10.1016/j.ajem.2018.12.001. Epub 2018 Dec 3. PMID: 30553634.
  10. Cole JB, Knack SK, Karl ER, Horton GB, Satpathy R, Driver BE. Human Errors and Adverse Hemodynamic Events Related to “Push Dose Pressors” in the Emergency Department. J Med Toxicol. 2019 Oct;15(4):276-286. doi: 10.1007/s13181-019-00716-z. Epub 2019 Jul 3. PMID: 31270748; PMCID: PMC6825064.
  11. Schwartz MB, Ferreira JA, Aaronson PM. The impact of push-dose phenylephrine use on subsequent preload expansion in the ED setting. Am J Emerg Med. 2016 Dec;34(12):2419-2422. doi: 10.1016/j.ajem.2016.09.041. Epub 2016 Sep 22. PMID: 27720568.
  12. Holden D, Ramich J, Timm E, Pauze D, Lesar T. Safety Considerations and Guideline-Based Safe Use Recommendations for “Bolus-Dose” Vasopressors in the Emergency Department. Ann Emerg Med. 2018 Jan;71(1):83-92. doi: 10.1016/j.annemergmed.2017.04.021. PMID: 28601272.
[cite]

More Posts From Dr. Hudlikar

COVID-19 and Hydroxychloroquine

~ Amita Sudhir, USA ~ Leave a comment

Authors: Nardos Makkonen, MD and Amita Sudhir, MD
University of Virginia, USA

Life does not choose the logically best design to meet a new situation. It adapts what already exists...The result, unlike the clean straight lines of logic, is often irregular, messy.

John Barry

In The Great Influenza, The story of the Deadliest Pandemic in History, the author John Barry states, “Life does not choose the logically best design to meet a new situation. It adapts what already exists…The result, unlike the clean straight lines of logic, is often irregular, messy.” This has never been more evident than now as the way we practice medicine changes fundamentally in the face of a new pandemic. While the news of a novel coronavirus spread, many in the scientific community found themselves struggling to find answers. In the wake of the pandemic, multiple studies were published aiming to identify risk factors, disease progression, and most importantly, therapeutic options.

As the number of positive cases grew exponentially, so did the urgency to find an effective therapy. Scientists and medical professionals were tasked with finding a swift solution. In addition to vaccine development, trials looking at the effectiveness of previously existing antiviral medications against SARS-CoV-2 were underway. A number of in-vitro models showed promising results – existing antiviral and antimalarial medications, including Hydroxychloroquine and Remdesivir, were noted to have cytotoxic properties against the novel coronavirus (1, 2). At first, it was difficult to tell how this could shape the management of affected patients. Then came a study that would change the global conversation on COVID therapies.

covid19

An article published on March 20th in the International Journal of Antimicrobial Agents looked at the effect of hydroxychloroquine and azithromycin on COVID positive patients. The study was an open-label, non-randomized clinical trial of thirty-six patients; twenty patients were treated with hydroxychloroquine, while sixteen were in the control group. The article looked at SARS–CoV-2 clearance from the nasopharynx after six days. Higher frequency of viral clearance was reported in the treatment group, hydroxychloroquine (plus azithromycin if deemed necessary) versus an untreated control group [14 out of 20 (70%) vs. 2 out of 16 (13%); P < 0.001]. The authors concluded that the addition of azithromycin to hydroxychloroquine was significantly more efficient for virus elimination (3). Multiple articles were published that questioned various aspects of the original article. Nonetheless, the original excitement surrounding the medication led to its widespread use for treatment of COVID positive patients in various hospitals across the world. However, in the ensuing months, multiple additional studies have been published that have informed our understanding of hydroxychloroquine as a treatment option for SARS–CoV-2, suggesting that it may not be the panacea that the initial study suggested it is.

One of the first randomized control trials on the topic was a multicenter, open-label, randomized control trial looking at 150 patients. Seventy-five patients were assigned to hydroxychloroquine plus standard of care, while the other 75 were assigned to standard of care alone. The primary endpoint of this study was looking at viral clearance by 28 days. The results suggested hydroxychloroquine was not associated with a significantly higher probability of negative conversion than the standard of care alone (4). In another retrospective cohort study of 1438 patients hospitalized in metropolitan New York, treatment with hydroxychloroquine, azithromycin, or both did not result in a significantly lower in-hospital mortality (5). A meta-analysis looked at eleven studies, including three randomized controlled trials and eight observational studies. Here, 2354 patients received hydroxychloroquine alone or in combination, while 1952 did not. The study found no significant difference in clinical progression, mortality, or viral clearance by RT-PCR among patients with COVID-19 infection who are treated with hydroxychloroquine compared with control groups (6). In addition, a significantly higher incidence of adverse events associated with hydroxychloroquine use across a number of studies was noted.

Adverse effects were also noted in a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. The findings show no confirmed benefit of hydroxychloroquine or chloroquine when used alone or with a macrolide on in-hospital outcomes for COVID-19. Notably, each of these drugs was found to be associated with decreased in-hospital survival and increased frequency of ventricular arrhythmias (7). Importantly, the Lancet has since released a letter of concern on 6/2/20 regarding its publication of this multinational registry analysis (8).

Beyond its potential therapeutic use for known COVID positive patients, hydroxychloroquine was touted as beneficial for prophylactic use. Prior to the publication of significant studies on the prophylactic efficacy of the medication, the Indian Council of Medical Research, under the Ministry of Health and Family Welfare, recommended chemoprophylaxis with hydroxychloroquine for asymptomatic health-care workers treating patients with suspected or confirmed COVID-19, and for asymptomatic household contacts of confirmed cases. The announcement led some in the scientific community to express concern, stating “the drug is untested, the benefits unknown, and the risks not negligible” (9). This concern was substantiated in subsequent studies. A recent randomized, double-blind, placebo-controlled trial analyzed the effect of hydroxychloroquine in postexposure prophylaxis. The study included 821 asymptomatic participants. 87.6% of the participants (719 of 821) had a high-risk exposure to a confirmed COVID contact. The primary outcome was symptomatic illness confirmed by a positive molecular assay or, if testing is not available, COVID-related symptoms. The results noted no significant difference in the primary outcome between participants receiving hydroxychloroquine (49 out of 414 [11.8%]) and those receiving placebo (58 out of 407 [14.3%]) (10). Additionally, side effects were noted to be more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%).

On May 27th, Dr. Anthony Fauci, the director of National Institute of Allergy and Infectious Diseases, when asked about hydroxychloroquine, stated that “The scientific data is really quite evident now about the lack of efficacy.” As of now, the World Health Organization is planning on resuming Hydroxychloroquine clinical trials after previously halting studies due to safety concerns (11). One adage often repeated in medicine is that what we learn now may not apply in 10 years. In the age of COVID, what we learn now may not apply in the next few months or even weeks. Seeing images of ventilated patients, and at times dead bodies across hospital hallways have filled us all with a deep desire for a quick fix. As physicians, we are likely to grasp at any straws that might help us fight this disease; we have to be careful to look critically at the evidence. Hope springs for a cure with each new study, but we should apply the same rigorous scientific methodology to COVID that we have developed for other diseases. As we move towards alleviating the suffering of this pandemic, it is essential to avoid falling into pitfalls and causing more harm along the way.

References and Further Reading

  1. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-271.
  2. Liu J, Cao R, Xu M, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16.
  3. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020;:105949.
  4. Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;369:m1849.
  5. Rosenberg ES, Dufort EM, Udo T, et al. Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State. JAMA. 2020;
  6. Chacko J, Brar G, Premkumar R. Hydroxychloroquine in COVID-19: A systematic review and meta-analysis. 2020. doi:10.1101/2020.05.14.20101774
  7. Mehra MR, Desai SS, Ruschitzka F, Patel AN. Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. The Lancet. 2020. doi:10.1016/s0140-6736(20)31180-6.
  8. Editors TL. Expression of concern: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. The Lancet. 2020. doi:10.1016/s0140-6736(20)31290-3.
  9. Rathi S, Ish P, Kalantri A, Kalantri S. Hydroxychloroquine prophylaxis for COVID-19 contacts in India. Lancet Infect Dis. 2020;
  10. Boulware DR, Pullen MF, Bangdiwala AS, et al. A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19. N Engl J Med. 2020;
  11. BerkeleyJr. World Health Organization resumes coronavirus trial on malaria drug hydroxychloroquine after examining safety concerns. CNBC. https://www.cnbc.com/2020/06/03/world-health-organization-resumes-coronavirus-trial-on-malaria-drug-hydroxychloroquine-after-safety-concerns.html. Published
[cite]