Chapter 24. Airway Management in a Patient with Angioedema

This 25-year-old black woman presents to the emergency department (ED) 2 hours after the onset of lip swelling that has progressed to difficulty in breathing. With the exception of newly diagnosed hypertension, she is otherwise well. Last week, her primary care physician began a course of a new antihypertensive medication, lisinopril. She has had no history of swelling and there is no family history of disorders characterized by swelling. Her vital signs are temperature 37°C, heart rate (HR) 100 beats per minute (bpm), respiratory rate (RR) 22 breaths per minute, blood pressure (bp) 165/90 mm Hg, and SpO2 is 99% on 2 L·min−1 of O2 by nasal prongs.

The patient is seated (Figure 24-1) with markedly edematous lips. She has a muffled voice (hot potato voice) and is unable to swallow her own secretions due to the swelling. There is no stridor. The remainder of the physical examination is unremarkable.

24.2.1 What Is the Pathophysiology of Angioedema?

Angioedema is defined as the abrupt onset of non-pitting swelling of the skin, mucous membranes, and deep subcutaneous tissues, including the linings of the upper respiratory and intestinal tracts.1 Angioedema develops because of a local increase in permeability of the submucosal or subcutaneous capillary vessels, causing local plasma extravasation. This is exacerbated by the release of vasoactive substances such as histamines, prostaglandins, bradykinins, and cytokines.2 Angioedema can be divided into hereditary angioedema (HAE) and acquired angioedema.

Hereditary angioedema is extremely rare, affecting 1 in 50,000 people.2 It develops due to a C1 esterase inhibitor deficiency, which is inherited in an autosomal dominant pattern. This deficiency results in an abnormal increase in the activation of C1 and subsequently excessive formation of the enzyme kallikrein. The excess kallikrein transforms kininogen into kinins, including bradykinin. Bradykinin is highly vasoactive and produces the characteristic tissue swelling.2 HAE is commonly precipitated by trauma and stress, and can recur. If the patient has known HAE, then treatment with fresh frozen plasma (FFP) is beneficial, as it contains C1 esterase inhibitor. In some centers, vapor-heated C1 inhibitor concentrate is available and is proving beneficial in recurrent attacks of HAE.2

Acquired angioedema is due to faulty activation of the complement and kallikrein–kinin systems. It comprises several types, including the traditional IgE-mediated allergic response, precipitated by exposure to an allergen (such as peanuts, antibiotics, and shellfish). Anaphylaxis is characterized by an acute onset and not only causes angioedema of the upper airways but also has a more systemic effect causing wheeze secondary to bronchoconstriction and hypotension secondary to vasodilation and third spacing.3 Anaphylaxis (or anaphylactoid) reactions can cause angioedema through other mechanisms such as direct mast cell degranulation (opiates, radio-contrast media) or by altering arachidonic acid metabolism (benzoates, angiotensin-converting enzyme inhibitors [ACEIs], and nonsteroidal anti-inflammatory agents [NSAIDs]).4,5

The development of angioedema secondary to ACEIs is of particular interest.4,5 In addition to inhibiting the conversion of angiotensin I to angiotensin II, the suppression of ACE results in a decrease in the breakdown of bradykinin and substance P. As outlined earlier, this can result in severe tissue swelling.1 ACEI-induced angioedema has a predilection for the head and neck,2 rendering it a particular challenge in airway management. It appears that this drug effect is associated specifically with the class of drugs known as ACEIs,2 although recently, angioedema has been demonstrated to occur with the angiotensin II receptor blockers (ARBs) as well.6,7 Treatment with IV steroids, antihistamines, and subcutaneous epinephrine (0.3 mg) may be beneficial in allergy-induced angioedema, but has been shown to be ineffective in HAE and of limited use in ACEI and ARB-induced angioedema.7,8 There is no role for FFP in ACEI or ARB-induced angioedema.

ACEI-induced angioedema affects more women than men in the United States and is most common among 40- to 50-year-olds. Close to half of those affected with angioedema are African American.9 According to the literature, the incidence of ACEI-induced angioedema ranges from 0.1% to 0.2% of all patients taking this class of drugs.1,2,10 However, ACEI-induced angioedema is the most common cause of angioedema seen in US EDs, accounting for 17% to 38% of all angioedema cases.11 In the omapatrilat (a new ACEI) versus enalapril (OCTAVE) trial, the investigators found that there was an increased incidence of the disorder in African American patients, those older than 65, and those with a history of drug rash or seasonal allergies.10 Approximately 50% of all ACEI-induced angioedema cases occur within 1 week of starting the medication, with the remainder occurring anywhere from weeks to years after starting the drug.2

24.2.2 What Is the General Clinical Course of the Disorder?

Patients with HAE usually report trauma, often minor (eg, dental visit), followed by tissue swelling. They can present with swelling in such widespread anatomic areas as the face, hands, arms, legs, GI tract, and genitalia, but often respond to treatment. In one large series, 10% of the patients with HAE required definitive airway intervention because of upper airway edema. The onset of IgE-mediated anaphylaxis is rapid and often life threatening if not treated appropriately.2 The clinical course of ACEI-induced angioedema is often subacute but always extremely unpredictable, and life-threatening presentations requiring airway interventions do occur and are reported in up to 20% of these patients.2 According to the literature, between 0 and 22.2% of patients with angioedema will require intubation.9 It is extremely difficult to predict which patients who present with a stable airway will progress to a requirement for airway intervention. Researchers from Boston9 retrospectively analyzed cases of ACEI-related angioedema and determined that increasing age and oral cavity/oropharyngeal involvement predicted the need for airway intervention. These predictors had a sensitivity of 65.2% and specificity of 83.7%.

Since the clinical course of angioedema, especially ACEI-induced, is very unpredictable, it is recommended that these patients be admitted to an environment where they can be closely monitored for at least 24 hours.

24.2.3 What Investigations Might One Employ to Aid in the Diagnosis and Evaluate the Severity of the Disorder?

The severity of airway compromise on presentation will determine the extent of initial investigations of these patients, and thus the workup for HAE is typically undertaken after the acute episode has resolved. The unpredictable clinical course of this disorder demands that each of these patients be triaged as emergencies to a resuscitation area of the ED and attended to immediately by nursing and physician staff. Evaluation and management are carried out concurrently, as is appropriate in patients with life-threatening conditions. As a result, early airway intervention is strongly advised. It is often obvious that the airway is in immediate jeopardy and this should trigger calling for assistance and implementing a strategy to secure the airway, from either above or below (surgically). The decision for airway intervention will be based largely on the clinical signs of respiratory distress: air hunger, agitation, hypoxia, and especially muffled voice, difficulty swallowing saliva, and stridor.

If one has the luxury of time and possess the skill, severity may be assessed by flexible nasopharyngoscopy.12 It is prudent to prepare for this procedure as though one were intending to perform an awake endoscopic-guided nasal intubation. This assumes that one has anesthetized the nasopharyngeal passage and inserted a nasotracheal tube through which the endoscope is passed in case the findings mandate intubation. It is preferable that the scope used for this procedure be of sufficient length and stiffness to guide an endotracheal tube into the trachea.12 Repeated nasopharyngoscopic evaluation at regular intervals may be indicated in the event immediate endotracheal intubation is not necessary. Additionally, as with all upper airway emergencies, it is prudent to be prepared to undertake an immediate surgical airway in the event that diagnostic maneuvers trigger complete upper airway obstruction. This is often referred to as a double set-up in the context of airway management.

A portable cross-table soft tissue x-ray of the airway is seldom useful and it should be emphasized that this investigation must not delay care if the airway is compromised and must not mean that the patient has to leave the resuscitation area. These patients are always reluctant to lay flat for studies, such as CT scanning and MRI evaluations to be performed. This hesitancy ought to alert the practitioner that the degree of airway obstruction is significant, rendering such studies contraindicated. Arterial blood gases and other laboratory investigations are generally not helpful in the management of these patients.

24.3.1 How Does One Decide that Intubation Is Indicated?

This decision is most often made on clinical grounds and is based on the degree of upper airway obstruction present, and the pace at which it changes. Diagnostic studies, with the possible exception of flexible endoscopic evaluation of the airway, are not usually helpful in deciding when to intubate. As mentioned earlier, early airway intervention is the safest course of action,13 particularly as the clinical course may be erratic and unpredictable. Although securing the airway should be the priority, some practitioners may consider a course of steroids and nebulized epinephrine in the hope of halting or reversing the progression of airway compromise.

Any evidence of upper airway obstruction, including a muffled voice, difficulty managing secretions, or stridor, ought to trigger urgent airway intervention. Other clinical signs motivating immediate intervention include: air hunger (dyspnea), confusion, agitation, or falling oxygen saturations.14

24.3.2 How Should the Airway Be Evaluated for Difficulty?

These airways should always be considered difficult and managed according to the Difficult Airway Algorithm (see Chapter 2). Specifically, they fail the MOANS analysis (see Section 1.6.1) for difficult bag-mask-ventilation in that mask seal may be inadequate. But more importantly, adequate gas exchange may be prevented by edematous upper airway tissue, occluding the airway even in the face of high pressures generated by bag-mask devices. Gas exchange at the alveolar level may also be compromised by bronchoconstriction and increased fluid and secretions.

Based on the airway evaluation using the mnemonic RODS (see Section 1.6.3), the use of extraglottic devices (EGDs) will be difficult. Insertion of the device may not be possible and the larynx itself may be edematous to the point of obstruction. Furthermore, the EGD may not provide an effective seal in an edematous hypopharynx.

The failure of MOANS and RODS alone prohibits the use of paralytic agents, even if one felt that the LEMON analysis (see Section 1.6.2) might permit successful direct laryngoscopy and intubation. In other words, rapid-sequence intubation (RSI) is imprudent. An assessment for cricothyrotomy is appropriate in these patients, as this procedure may emerge as the preferred and primary intervention for airway management and may be performed awake under local anesthesia. In other words, if laryngoscopy is unsuccessful or impossible in a patient who is very difficult to ventilate using a bag-mask, and alternative intubating techniques, and extraglottic rescue devices are unlikely to work, the surgical option has to be considered early in the planning and execution of airway management.

24.3.3 How Should This Patient's Airway Be Managed?

Some patients with angioedema have had prior episodes and may be able to provide some reassurance that this episode will resolve under close observation. However, such patients are few and the course of this disease is unpredictable. It is much more likely that the clinical course will be unpredictable and a more aggressive approach to airway management is therefore justified.

Management is driven by the Difficult Airway Algorithm (see Chapter 2). In the event that oxygen saturations are poor and cannot be improved, one is directed to the Failed Airway Algorithm and immediate cricothyrotomy. RSI is rarely an option in these patients. If there is time, the next step will depend on the practitioner's access to, and ability to use, a flexible bronchoscope (FB). If an experienced practitioner is available, then intubation using FB ought to be performed with immediate cricothyrotomy as backup. The nasal route for the FB-guided intubation mentioned earlier is ordinarily much easier for those who infrequently perform intubations. In the event one does not have, or cannot use, a flexible bronchoscope then an awake look employing a conventional laryngoscope may help create a more informed decision to intubate awake or to move to cricothyrotomy.

It is a difficult decision to use sedative hypnotic agents to facilitate airway evaluation and management in patients with upper airway obstruction in general and angioedema in particular. Patients with upper airway obstruction maintain their airways by using every airway muscle at their disposal, and even small doses of these sedative agents may precipitate a complete upper airway obstruction. In small titrated doses, ketamine may be preferable in that it maintains muscle tone and respiratory drive. The disadvantages of laryngeal sensitization, salivation, and confusion must be weighed against the positive aspects of using this drug.

The use of topical local anesthetic agents in patients with upper airway obstruction is also not without risk. Several cases have been reported in the last decade of topicalization converting partial upper airway obstruction to complete obstruction (see Section 3.3.2.1). However, a practitioner may have no choice but to employ topicalization in an attempt to secure the airway. Blind (nonvisual) techniques such as blind nasal intubation and light-guided techniques are relatively contraindicated due to the potential for airway distortion and the risk of producing further trauma and bleeding.

The incidence of angioedema has increased dramatically over the past two decades with the introduction of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) for the treatment of hypertension. The clinical course of an episode is unpredictable. For this reason, securing the airway early is generally a safer course than watching and waiting. Available therapies, including intravenous steroids and nebulized alpha agonists (eg, epinephrine), are of marginal value and ought not delay airway intervention. Intubation over a flexible bronchoscope may be the preferred technique, the nasal route being recommended for those who perform flexible bronchoscopic intubation infrequently. Alternatively, employing sedation and topical anesthesia may enable one to intubate using direct laryngoscopy. However, the Plan B option of cricothyrotomy performed under local anesthesia with the patient awake must be considered as a backup, or in some cases, even a primary method of securing the airway.

As with all cases of upper airway obstruction, one must appreciate that while the patient may have stable vital signs, the airway is exceedingly unstable!