Anaphylaxis: Keys to Prehospital Success
Anaphylaxis is a life-threatening condition for which prehospital intervention has been definitively shown to improve both short-term and long-term patient outcomes [1, 2]. It is also a condition that is vulnerable to management complacency among providers, as reactions occur in varying degrees of severity and are frequently mild. The lifetime individual risk for anaphylaxis is estimated to be between 1-3%, and recent evidence suggests that its incidence is rising . Furthermore, this number is likely underestimated due to underdiagnosis, and failure of reporting [3, 4].
The reaction is fatal in up to 2% of cases [6,7] and fatality is impossible to predict, though high-risk patients can decrease their risk by avoiding triggers, and increase their chance of survival by carrying epinephrine at all times. For those not carrying a diagnosis of severe allergies or without access to personal epinephrine, prehospital administration of epinephrine is especially important .
In 2015, the World Allergy Organization presented good evidence suggesting that epinephrine is underutilized in the prehospital treatment of anaphylaxis. While the reasons for this are likely multifactorial, it is unequivocal that prehospital administration of epinephrine is a strong contributor to patient outcome [1-5, 8].
An erroneous belief exists that epinephrine “fixes” anaphylaxis, thereby obviating the need for further evaluation and treatment in the emergency department. To undermine this belief, one must consider the pathogenesis of anaphylaxis .
Anaphylaxis results from the cascade-like activation of immune cells in the body after exposure to a particular allergen. The most common triggers for fatal reactions are foods, drugs, and stings [1, 10]. Children and adolescents carry a higher risk of fatal anaphylaxis due to food reactions, while older individuals are more likely to die from venom or drug reactions [8, 10, 11]. The triggering allergen starts the reaction by stimulating a response in a particular type of antibody (IgE), which bind both the allergen and sites on the surface of mast cells and basophils (immune cells), causing their activation. The activated immune cells quickly release a variety of potent chemicals into the body, including histamine and tryptase. As the reaction progresses, the reaction becomes increasingly inflammatory. Importantly, the first exposure to an allergen may not result in anaphylaxis, as the body must first become sensitized to the allergen so that it is primed for an explosive response upon repeat exposure.
This chemical reaction is the root cause of anaphylaxis, and cannot be stopped once initiated. Physiologically, the massive histamine release causes peripheral vasodilation, increased vascular permeability, increased heart rate, and bronchoconstriction.
As the chemical reaction cannot be stopped, treatment is primarily directed toward optimizing the patient’s hemodynamics until the condition abates.
Blood Pressure = (Cardiac Output) x (Systemic Vascular Resistance)
As anaphylactic shock is a form of distributive shock caused by systemic vasodilation, hypotension is primarily secondary to a drop in systemic vascular resistance.
As anaphylaxis is a systemic event, it is manifested in multiple organ systems.
Cardiovascular: Hypotension, tachycardia, and dysrhythmias.
Pulmonary: Bronchospasm, dyspnea, pulmonary edema, laryngeal edema, hypoxemia, and cough.
Dermatologic: Urticaria, facial edema, and pruritus.
In mild cases, there may only be urticaria. In severe cases, there can be cardiovascular collapse, sometimes with severe bronchospasm . The most common presentation involves sudden onset urticaria, angioedema, flushing, and pruritus. Skin findings are absent in 10—20% of cases . Fatal reactions may kill as quickly as 30 to 60 minutes after allergen exposure, and biphasic reactions may be fatal up to 8-10 hours after symptoms have resolved [8, 14, 15].
Patients with severe food allergies are frequently aware of their allergen from prior exposures. Medicine and venom are more likely to produce fatal first-exposure reactions, though they may also cause clinically silent sensitization in early, pre-fatal exposures [8, 10, 11, 13].
Food-induced reactions in children and teenagers are more frequently fatal due to rapid loss of the airway and respiratory arrest, while drug- and venom-induced reactions in older adults are more frequently associated with cardiovascular deterioration and shock. These trends are important to consider when anticipating clinical course [8, 16, 17].
Asthma is a well-studied risk factor for fatal anaphylaxis in children and teenagers, with cardiovascular disease and COPD loosely correlating to fatality in older adults [14, 17, 18].
Ultimately, anaphylaxis is a clinical diagnosis that requires a high index of suspicion to diagnose in the undifferentiated patient.
a. Respiratory compromise (ie. dyspnea, wheezing/bronchospasm, stridor, reduced expiratory flow, hypoxemia, etc.).
b. Reduced BP or associated symptoms of end-organ dysfunction (ie. hypotonia, syncope, incontinence, etc.).
/ or /
2. Two or more of the following that occur rapidly after exposure to a likely allergen (minutes to hours):
a. Involvement of the skin-mucosal tissue (ie. generalized hives, itching/flushing, swollen lips/tongue/uvula, etc.).
b. Respiratory compromise (ie. dyspnea, wheezing/bronchospasm, stridor, reduced expiratory flow, hypoxemia, etc.).
c. Reduced BP or associated symptoms of end-organ dysfunction (ie. hypotonia, syncope, incontinence, etc.).
d. Persistent gastrointestinal symptoms (ie. crampy abdominal pain, vomiting, etc.).
/ or /
3. Reduced BP after exposure to known allergen (minutes to hours):
a. Infants and Children: Low systolic BP** (age-specific) or drop of >30% in systolic BP.
b. Adults: Systolic BP of less than 90mmHg or drop of >30% from the person’s baseline.
** Low systolic blood pressure for children is defined as: <70mmHg from 1 month to 1 year, <(70 mmg Hg + [2 x age]) from 1 year to 10 years, and <90mmHg from 11 year to 17 years.
Ann Emerg Med. 2006;47:373-380.
The initial management of anaphylaxis is the same for all cases, regardless of the type of allergen:
- Remove exposure to the allergen, if possible.
- Administer oxygen.
- Assess airway and breathing.
- Intubate the patient, if necessary.
- Intubate early if there is evidence of obstruction due to angioedema.
- Surgical airway may be necessary for severe cases.
- Administer epinephrine.
- Stable: 0.3-0.5 mg IM every 5-10 min, repeated three times as needed.
- Unstable: 0.3-0.5 mg IM every 5 min until an IV or IO is established, then 2-10 μg/min drip.
- Administer 1-2 L normal saline bolus.
- Administer H1 blocker (Benadryl [diphenhydramine]) 50-100 mg AND H2 blocker (ie. ranitidine) 50 mg.
- Administer steroids: methylprednisone 125 mg IV – OR – dexamethasone 1-5 mg/kg IV.
- Consider nebulized Albuterol.
- For cardiac arrhythmia or cardiac arrest, follow ACLS protocol.
- ALS transport to nearest Emergency Department.
Algorithm adapted from Simons et al. Anaphylaxis. J Allergy Clin Immunol 2010; 125:S161.
0.01 mg/kg IM. For kids <25kg, use a standard dose of 0.15 mg IM.
α1 agonism causes vasoconstriction which mitigates edema and combats hypotension.
β1 agonism causes increased rate and force of cardiac contractions, to help combat hypotension.
β2 agonism causes bronchodilation and decreased release of histamine from mast cells.
In addition to the importance of administering epinephrine in critically-ill patients, there is good evidence that well-appearing patients also benefit from epinephrine. Administration before ED arrival significantly reduces the likelihood of hospital admission when compared with administration after ED arrival [8, 19, 20]. Treatment failure in fatal anaphylaxis is closely tied to the speed with which epinephrine is administered. Major factors that are known to delay the therapeutic action of epinephrine include misdiagnosis, improper administration, and lack of access to the drug [1, 8, 16, 17].
Yes, according to primary sources. There appears to be an increased risk of complication when epinephrine is given via the intravenous route in the setting of anaphylaxis . Therefore, IM administration is the recommended route for everybody [7, 8, 20].
There is NO absolute contraindication for the administration of epinephrine in anaphylaxis [10, 21].
Zlatan Coralic, PharmD described the “Dirty Epi Drip” in ALiEM in 2013. The idea is to quickly and easily initiate an epinephrine drip for a patient in anaphylactic shock. The dosing is intended to approximate the recommended dose** of push-dose epi (100mcg over 5 min, or 20mcg/min).
**Recommendations from Circulation. 2005;112:IV-143-IV-145.
The goal is to create a solution concentration of 1mcg/mL, and then administer it “wide-open”. This presumes that an 18-gauge IV would flow at approximately 20-30mL/min, yielding an infusion rate of 20-30mcg/min (similar to push-dose rate) .
Here’s the technique:
Step 1: Inject 1 mg of epinephrine into a 1,000 mL normal saline bag (final solution concentration 1 μg/mL). Doesn’t matter if you start with 1:1000 or 1:10000.
Step 2: Run drip wide open until the patient’s hemodynamics stabilize.
While the technique certainly represents a viable way to get epinephrine quickly into the patient, we were dubious about how reproducible the ‘wide-open’ flow rate would be. To be fair, the author acknowledges that significant variability can occur depending on catheter size, IV bag height, and squeeze on the bag.
To consider just how variable this flow might be, we used the flow rates that were quoted in our recent article on IV catheter size and flow.
When considering that data, the rate of administration of epinephrine with an 18ga catheter held ‘wide-open’ is nearly 5x the recommended dose (~98.1 mcg/min).
With this in mind, we would agree with the original author that this technique MUST be coupled with aggressive monitoring and rapid titration to the patient’s response. It also MUST be considered temporizing, at best, until a medication pump can be utilized.
There may be a need for a second vasopressor in patients with severe and refractory anaphylactic shock. It is critical to monitor these patients closely, as they are at increased risk for adverse outcomes [10, 12].
In patients who take beta blockers, epinephrine may have a reduced therapeutic effect. Glucagon may be considered, as it can activate the same adrenergic receptors through a different pathway .
There is strong evidence to suggest that prehospital providers can improve patient outcome through early identification and treatment of anaphylaxis. Identification of anaphylaxis requires a high index of suspicion, as its presentation can be variable. If suspected, epinephrine should be administered early.
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