VOLUME 30, ISSUE 2

Divya Janardhanan, MD

CA1 Resident
Baylor College of Medicine
Houston, TX

Jaime Ortiz, MD

Associate Professor of Anesthesiology
Baylor College of Medicine
Houston, TX

Evaluation and Management of Anaphylaxis During Induction of Anesthesia

Background

Anaphylaxis is a rapid-onset systemic hypersensitivity reaction that can be life-threatening. The incidence of anaphylaxis during anesthesia has been reported to range between 1 in 4000 to 1 in 25,000.1 The consequences of perioperative anaphylaxis can be severe. Estimates of the mortality rate range from 1.4 to 6 percent, and perioperative anaphylaxis accounts for approximately 5 to 7% of all deaths during anesthesia.2 It can be classified into 4 grades based on severity of symptoms. Grade I includes cutaneous manifestations, grade II includes all symptoms that are not life threatening, grade III include symptoms such as arrhythmias and bronchospasm, and grade IV includes severe manifestations such as cardiac and respiratory distress.2 Perioperative anaphylaxis, specifically due to induction agents, is becoming more common; likely secondary to better reporting and the increased complexity of anesthetic regimens.2 It is very important to identify and manage perioperative anaphylaxis in a timely manner to minimize the potential complications that can occur. In this discussion, we will explore the most commonly implicated agents and how to evaluate and manage patients presenting with acute anaphylaxis.

Risk Factors

There are a number of risk factors that are associated with increased likelihood of perioperative anaphylaxis. These include a previous history of allergic reaction during anesthesia, multiple surgeries, latex allergy (including allergies to avocado, kiwi, banana, papaya, chestnut, or buckwheat that can potentially cross react with latex), children with spina bifida who have had multiple surgical interventions, and hereditary angioedema.2 Asthma is considered a risk multiplier in anaphylactic reactions as the risk of life-threatening bronchospasm during anaphylaxis can be increased over 6 fold in patients with pre-existing asthma.3 Uncontrolled asthma should be managed prior to any elective procedures to avoid potentially severe pulmonary manifestations of an allergic reaction.2

Triggering Agents

Patients are exposed to a number of different triggers prior to and during induction of anesthesia. In cases in which a trigger was identified, the most common causes were neuromuscular blockers (NMB), antibiotics, and latex. 4 Approximately 50 to 70% of all anaphylaxis cases were due to NMB’s with rocuronium and succinylcholine being the most commonly implicated agents.2 NMB’s can cause anaphylaxis through both IgE-mediated and non-immunologic direct mast cell activation.2

IgE sensitization to the tertiary and quaternary ammonium groups found on NMB’s can occur and can be a result of previous exposure to various products that contain these tertiary and quarternary groups including topical cosmetics, personal products, and a variety of medications.2 The previous exposure to these products is thought to be the reason that anaphylactic reactions are more common in women.4 Latex is the second most common trigger identified causing perioperative anaphylaxis, however, many hospitals have established a latex-free environment with a resultant decrease in the incidence of these reactions.2 Children with a history of multiple surgeries and invasive procedures involving exposure to latex products (such as frequent urinary catheterization seen with spina bifida patients) are known to be at a greater risk for sensitization that can result in anaphylaxis.Antibiotics such as vancomycin or beta lactams are also frequently implicated. The highest cross reactivity between antibiotics occurs between cephalosporins and penicillins.4 Vancomycin reactions are more commonly related to high infusion rates leading to direct histamine release resulting in “red man syndrome,” which, unlike IgE mediated anaphylactic reactions, can occur with the first administration of the drug.2 It should be noted that “red man syndrome” is an anaphylactoid reaction and is distinctly different than the IgE mediated anaphylactic reaction that may also be caused by vancomycin.

Other causes of perioperative anaphylaxis include intravenous anesthetic induction agents and opioids. Anaphylactic reactions to ketamine and etomidate are extremely rare.2 However, patients with atopy (a genetic predisposition to develop an allergic reaction and produce elevated levels of IgE upon exposure to an environmental antigen) are thought to be predisposed to having nonspecific histamine release when exposed to ketamine.2 Propofol can cause both IgE-mediated mast cell activation and, more commonly, non-immunologic direct mast cell activation leading to histamine release.2 This phenomenon is thought to be more prevalent with the presence of NMB’s. Patients with soybean or egg allergies are listed as having a contraindication to propofol as the vehicle for propofol is a soybean oil emulsion with egg phosphatide and glycerol. However, the vast majority of patients with this allergy have been shown to tolerate propofol without any complications.5 Opioids, such as morphine and fentanyl, are a rare cause of allergic reactions, with most reactions being related to non IgE-mediated, nonspecific histamine release. The most common reactions involve urticaria, flushing, pruritius, and mild hypotension.2

Evaluation and Management

Evaluating and diagnosing perioperative anaphylaxis can be very difficult due to the patient being sedated, intubated, and having surgical drapes covering most of the skin. The first signs may be tachycardia and hypotension which can progress to bradycardia if the patient becomes hypoxemic or develops a heart block.6 Cardiovascular manifestations, ranging from hypotension to cardiac arrest, are the first detected manifestations in up to 50 percent of cases.6 Bronchospasm and laryngeal edema may present as a sudden increase in peak pressures, an upsloping pattern in end tidal carbon dioxide waveform, or decrease in arterial oxygen saturation. Initial management should involve prompt epinephrine administration.2 Intramuscular administration is preferred over intravenous (unless the patient is presenting in cardiovascular collapse) due to lower risk of arrhythmias and hypertension.2 Fluid resuscitation should also be promptly initiated as the patient can develop large fluid shifts. Other agents, which are not life-saving but can be given as adjunctive therapies, include H1 and H2 antihistamines, bronchodilators, and glucocorticoids.2 A tryptase level should also be sent as soon as possible. Elevated levels of more than 25 μg/L one to six hours after suspected anaphylaxis suggests mast cell activation and mediator release and supports the diagnosis.7 A normal level, however, does not rule out anaphylaxis.4 Elevated plasma histamine levels can also be found in acute anaphylactic reactions if checked within minutes of the reaction.7 The patient should also be referred to an allergy specialist for further evaluation post operatively for allergy testing.8

Conclusion

Anaphylaxis following induction of anesthesia is a rare but potentially deadly reaction. Prompt diagnosis and management can be critical to avoiding cardiovascular and respiratory collapse. Identifying high risk patients and recognizing the presence of high risk situations such as use of NMB’s or the presence of latex are the key to early recognition and treatment of intraoperative anaphylaxis. If an anaphylaxis event is suspected, close follow up and referral to an allergy and immunology specialist is recommended to identify triggering agents and avoid future episodes of anaphylaxis.8

References

  1. Mali S. Anaphylaxis during the perioperative period. Anesth Essays Res. 2012; 6(2): 124-33.
  2. Kannan JA, Bernstein JA. Perioperative anaphylaxis: diagnosis, evaluation, and management. Immunol Allergy Clin North Am. 2015; 35(2): 321-34.
  3. Summers CW, Pumphrey RS, Woods CN, et al. Factors predicting anaphylaxis to peanuts and tree nuts in patients referred to a specialist centre. J Allergy Clin Immunol. 2008; 121:632–638.
  4. Lieberman P., Nicklas R.A, Oppenheimer J., et al: The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010; 126: pp. 477-480.e1-42.
  5. Asserhøj LL, Mosbech H, Krøigaard M, Garvey LH. No evidence for contraindications to the use of propofol in adults allergic to egg, soy or peanut†. Br J Anaesth. 2016; 116(1): 77-82.
  6. Sampson HA, Muñoz-furlong A, Bock SA, et al. Symposium on the definition and management of anaphylaxis: summary report. J Allergy Clin Immunol. 2005;115(3):584-91.
  7. Mertes P.M., Tajima K., Regnier-Kimmoun M.A., et al: Perioperative anaphylaxis. Med Clin North Am 2010; 94: pp. 761-789.
  8. Galvao V.R., Giavina-Bianchi P., and Castelis M.: Perioperative anaphylaxis. Curr Allergy Asthma Rep 2014; 14: pp. 452.