Symptoms and signs
Generalized hives, itching or flushing, swollen lips, tongue, and uvula, periorbital edema, and conjunctival swelling
Nasal discharge and congestion, change in voice quality, throat swelling, stridor, shortness of breath, wheeze and cough. GI symptoms and throat swelling, stridor, shortness of breath, wheezing and cough.
Nausea, vomiting, diarrhea and crampy abdominal pain.
Syncope, dizziness, tachycardia, and hypotension.
The incidence of anaphylaxis during anesthesia is estimated to be from 1/4000 to 1/25,000 . Perioperative anaphylaxis occurs more often in women than in men, but occurs equally in both boys and girls . More than half of perioperative anaphylaxis cases were identified as immunoglobulin E (IgE)-mediated . Perioperative anaphylaxis is more likely to occur following anesthesia induction, but it can occur during the anesthesia maintenance and recovery period as well. The mortality from perioperative anaphylaxis is about 0–1.4% according to the most recent study . The detection of anaphylaxis under anesthesia can be challenging due to masked symptoms under anesthesia and anesthesia-induced cardiovascular disturbances. Most anesthetics, such as propofol, can cause hypotension.
28.6.2 Pathophysiology of Anaphylaxis
The mechanisms of anaphylaxis involve either an immunologic or non-immunologic reaction. The immunologic reaction can be divided into IgE-dependent and non-IgE-dependent reactions. The previous exposure to a trigger is required for IgE-mediated immunologic reactions. When antigens bind to IgE, IgE-mediated reaction activates mast cells and basophils to release inflammatory mediators such as histamine, leukotrienes, tryptase, and prostaglandin. In non-IgE-mediated mechanisms, the reaction is mediated through IgG or IgM antibody or antigen:antibody complex and complements. Non-immunologic mechanisms cause direct release of histamine or other mediators from mast cells and basophils. The release of these mediators lead to generalized urticaria, angioedema, bronchospasm, and hypotension. Excessive activation of vasodilator mechanisms results in vasodilation that leads to severe hypotension and cardiovascular collapse.
Many drugs can cause anaphylaxis during the anesthesia period, but the most common triggers of perioperative anaphylaxis are neuromuscular-blocking agents (NMBAs), antibiotics, latex, hypnotic agents, opioids, and colloids. Among them, NMBAs are the most identifiable causes of perioperative anaphylaxis. According to recent European studies, 50–70% of anaphylaxis cases related to anesthesia were due to NMBAs. Antibiotics appear to be the most common trigger of anaphylaxis during anesthesia in the United States .
NMBAs can cause anaphylaxis via both IgE-mediated and non-immunologic direct mast cell activation. The most implicated agents include atracurium, pancuronium, rocuronium, succinylcholine, and vecuronium. The ammonium ion of NMBAs is the main allergenic determinant. Anaphylaxis is more common with rocuronium and succinylcholine than with others. Suggamadex, a reversal agent for steroidal NMBAs (such as rocuronium) also causes anaphylaxis; cross activity exists among NMBAs.
Antibiotics are often used to prevent wound infections during surgery, and were responsible for 12–15% of identifiable triggers in European studies. But, it accounts for 50% of IgE-mediated reactions and is the most common cause of perioperative anaphylaxis in the United States. β(beta)-lactam antibiotics (including penicillins and cepholosporins and vancomycin) are the most common triggers. Βeta-lactam antibiotics cause IgE-mediated anaphylaxis while vancomycin causes a reaction secondary to direct histamine release from mast cells.
Latex anaphylaxis in the United States is less common since the introduction of latex-free products in surgical suites. However, occult exposure to natural rubber latex still accounts for a significant number of perioperative anaphylaxis. The latex allergy is an IgE-mediated process resulting from formation of a specific IgE against the protein in the natural rubber latex. The common latex resources are gloves, drains, and catheters. Latex allergy is likely to occur more often in patients with repeated exposure to latex gloves, or catheters from prior surgery or from occupational use, in patients with spina bifida, and in healthcare workers. Reactions to latex usually occur later in the surgical procedure, generally 30 min or more after the start of intervention.
Risk factors for perioperative anaphylaxis include the female sex, past history of anaphylaxis, allergic drug reactions, allergic conditions such as eczema or hay fever, multiple past surgeries and procedures, and mast cell disorders. Patients with asthma are at a greater risk for perioperative anaphylaxis.
28.6.4 Diagnosis of Anaphylaxis
Anaphylaxis is a clinical diagnosis, and can likely be diagnosed if one of following criteria is met:
Acute onset of illness (minutes to hours) involved on the skin, mucosal or both; either respiratory compromise or reduced blood pressure; or associated symptoms of end organ dysfunction.
Two or more of following that will occur rapidly after likely antigen exposure (minute to hours): (a) involvement of skin-mucosal tissue, (b) respiratory compromise, (c) reduced blood pressure (BP) or associated symptoms, (d) persistent gastrointestinal (GI) symptoms.
Reduced BP after exposure to a known antigen for that patient.
Airway edema manifested by onset of stridor.
Laboratory tests supporting a diagnosis of anaphylaxis consist of serum or plasma total tryptase and plasma histamine levels. Blood samples for tryptase measurement need to be obtained within 15 min and up to 3 h at the onset of symptoms. An elevated tryptase level highly predicts anaphylaxis, but non-elevated serum tryptase does not exclude anaphylaxis. Plasma histamine level typically peaks within 5–15 min after onset of symptoms and then declines to baseline after 60 min.
28.6.5 Severity Classification of Anaphylaxis
The severity of anaphylaxis is classified into 3 types based on the clinical manifestations:
Mild – involved in skin and subcutaneous tissue only
Moderate – involved in respiratory, cardiovascular, or gastrointestinal system
Severe – involved hypoxia, hypotension, or neurologic compromise
The Ring and Messmer 4-step grading scale classifies severity of anaphylaxis into four grades based on clinical presentations. Grade 1 involves cutaneous-mucosal signs, whereas grade 2 corresponds to mild cutaneous-mucous features that may be associated with cardiovascular and/or respiratory signs. Grade 3 involves cardiovascular collapse that may be associated with cutaneous-mucous signs and/or bronchospasms. Grade 4 is cardiac arrest. Grade 3 and 4 anaphylaxis are usually IgE mediated.
28.6.6 Perioperative Management of Anaphylaxis
Perioperative care depends upon the severity of anaphylaxis. Treatment during severe anaphylaxis should include cessation of anesthetic or drug, rapid volume resuscitation, and prompt epinephrine administration. Epinephrine is the first-line drug for anaphylaxis-induced cardiovascular collapse. The effects of epinephrine are mediated by both α(alpha)-adrenergic receptors and β(beta)-adrenergic receptors to produce vasoconstriction and an inotropic effect, and bronchodilation. Intravenous administration of 50–200 mcg epinephrine is recommended as an initial dose, followed by infusion as needed. Vasopressin is an alternative if epinephrine fails. Antihistamine receptor agents (such as diphenhydramine and cimetidine) and steroids (hydrocortisone) are second-line agents in the treatment of anaphylaxis.
28.6.7 Post-Anaphylaxis Evaluation
Patients who had perioperative anaphylaxis should be referred to an immunologist for evaluation to determine the offender, and to prevent recurrent reactions in future surgery . The safest perioperative care approach for patients with a past history of anaphylaxis is the definitive identification, and complete avoidance of the trigger. If the evaluation did not reveal a specific agent causing anaphylaxis, then general precaution includes avoiding beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and drugs that release histamine, slowing the administration rate of antibiotics, and optimizing patients with asthma. Alternate anesthesia with local or regional anesthesia may be chosen if it is appropriate for the procedure.
Laryngospasm is a sustained glottis closure of the vocal cords resulting in a partial or complete airway obstruction during light anesthesia. It is the most frequent cause of postextubation airway obstruction. If not treated quickly, it rapidly leads to hypoxia, hypercarbia, bradycardia, cardiac collapse, or even patient death.
The overall incidence is under 1% in both adults and pediatric patients, but laryngospasm occurs twice as often in pediatric patients between birth and 9 years old, while 3 times as often during the newborn to 3-month-old age. However, much higher incidence of laryngospasm (9%) is reported in pediatric patients with history of respiratory problems.
Glottic closure is a protective airway reflex that exists to prevent aspiration. A laryngospasm is an abnormal reflex that persists for a longer period. It is normally triggered by peri-glottic stimuli, mediated via the vagus nerve. Sensory fibers from the laryngeal mechanical, chemical, and thermal receptors ascend via the vagus nerve and via the internal branch of the superior laryngeal nerve (SLN). The motor response is mediated by the recurrent laryngeal nerve via the 3 intrinsic laryngeal muscles consisting of the lateral cricoarytenoids, thyroarytenoids, and cricoarytenoids. Glottis closure occurs by ether true vocal cord adduction alone or in combination of the false vocal cords. The supraglottic soft tissues are thought to impact the glottis as they are pulled down by an increasing translaryngeal pressure gradient during obstructed inspiratory effort.
28.7.3 Risk Factors for Laryngospasm
Anesthetic factors: Light anesthesia at the time of stimulus, the use of potent irritant volatile agents such as desflurane during induction, the presence of blood or secretion in the airway, instrumentation of airway in the light plane of anesthesia, LMA malpositioning, and extubation during light anesthesia.
Patient factors: Young age, upper respiratory infection (URI), hypersensitive airway due to conditions such as asthma and smoking, pre-existing airway abnormality, ex-premature infants under 1 year of age, whooping cough, obstructive sleep apnea, and gastroesophageal acid reflux are risk factors for increased laryngospasm.
Surgical risk factors: Upper airway surgeries, such as a tonsillectomy or an adenoidectomy, carry the greatest risk. Thyroid surgery and esophageal surgery also have higher risks.
28.7.4 Diagnosis of Laryngospasm
A laryngospasm must be considered if there is airway obstruction during anesthesia that was not relieved by basic airway maneuvers. Common signs of laryngospasm include inspiratory stridor, increased respiratory efforts, tracheal tug, desaturation with or without bradycardia, and airway obstruction that was not relieved by an upper airway device. Differential diagnoses are breath holding, bronchospasm, and pulmonary aspiration.
28.7.5 Management of Laryngospasm
Prevention of laryngospasm:
Patients with a higher risk for laryngospasm need to be identified preoperatively and it must be ensured that adequate depth of anesthesia is achieved before triggering any stimulus.
Inhalational induction should be carried out by using non-irritating agents, such as sevoflurane; IV induction with propofol is less associated with laryngospasm.
Patients can undergo deep extubation while placed in lateral position, with the head down to keep the vocal cords clear of secretions during emergence.
Pharmacological agents including magnesium, lidocaine, and atropine have been indicated to reduce the incidence of laryngospasm. Both topical and intravenous use of lidocaine is effective for preventing laryngospasm in children.
Once a laryngospasm is recognized, prompt therapy should be initiated and help may be called.
Treatment of laryngospasm:
Removing any triggering stimuli, relieving supra-glottic obstruction, removing obvious secretion and blood that is in the larynx, applying continuous positive airway pressure (CPAP) ventilation with 100% oxygen.
Jaw thrust and placement of a properly sized oral airway device will help to ensure the patency of the supra-glottic airway.
Larson’s maneuver, a forcible jaw thrust with bilateral digital pressure on the body of the mandible just anterior to the mastoid process, may resolve laryngospasm by clearing the airway and stimuli.
If CPAP and the holding maneuver fail to stop the laryngospasm, deepening anesthesia with propofol or other drugs is required to diminish the exaggerated glottis closure reflex.
Despite all efforts mentioned above, if the patient continues to desaturate and the laryngospasm is ongoing, a small dose of succinylcholine (0.1–0.5 mg/kg) should be given to break the laryngospasm. If no IV is available, intramuscular succinylcholine 4 mg/kg can be administered.
In the case of refractory laryngospasm, a superior laryngeal nerve block and trans-tracheal block through cricothyroid membrane with lidocaine may break the laryngospasm .
28.8 Aspiration of Gastric Contents
Perioperative pulmonary aspiration is defined as aspiration of gastric contents that occur after induction of anesthesia, during a procedure, or in the immediate period after surgery . Though it occurs infrequently, aspiration can lead to significantly increased morbidity and mortality rates. The incidence of aspiration during elective surgery is 1 per 2000–3000 anesthesia cases in adults and 1 per 1200–2600 anesthesia cases in children. However, a recent study demonstrated a much lower incidence of pulmonary aspiration with 1 per 4932 cases in pediatric populations. Most perioperative aspirations happen immediately after induction of anesthesia. However, pulmonary aspiration can occur prior to induction due to trauma, active vomiting, or preoperative sedation; it also can occur after extubation in the PACU, secondary to depressed consciousness from residual anesthetic effect. Silent aspiration can occur even while the patient is intubated with a cuffed endotracheal tube.
General anesthesia and anesthetics inhibit protective airway reflexes, including apnea with laryngospasm, coughing, expiration, and spasmodic panting that protects lungs from aspiration. Lower esophageal sphincter (LES) tone and barrier pressure are likely reduced under inhalational and propofol anesthesia. The upper esophageal sphincter (UES) of the cricopharyngeal muscle is reduced by most anesthetics, except ketamine. The depression of protective airway reflexes, in combination with reduction in LES and UES tone, make anesthetized patients prone to aspiration. Aspiration occurs once gastric contents (liquid or particulate matter, et al.) enter into the tracheobronchial tree as a consequence of passive regurgitation or active vomiting. Depending on the composite of aspirates, patients can experience different clinical consequences: (1) acid-associated aspiration pneumonitis, (2) bacterial infection, and (3) particle-associated aspiration.
28.8.2 Acid-Associated Aspiration Pneumonitis
Aspiration results in parenchymal damage in two phases. The first phase is marked by direct toxic damage to respiratory epithelium by acid. The second phase is marked by an acute inflammatory response. Aspiration of gastric acid induces a chemical burn, triggering the release of various inflammatory mediators such as cytokines, chemokines, and adhesion molecules. These mediators cause inflammatory response and attract neutrophils and alveolar macrophages to activate leukocytes.
Aspiration pneumonia is an infection process secondary to aspiration of oropharyngeal and gastric contents contaminated with pathogenic bacteria. It has a slow onset and occurs more in elderly patients and in patients on ventilator support in the ICU. Aspiration pneumonia accounts for at least 10% of community-acquired pneumonia.
Inhalation of gastric content particle matters can result in an acute obstruction of smaller (and possibly larger) airways with consequences of sudden arterial hypoxia and the development of atelectasis distal to the blockage site.
28.8.3 Risk Factors for Aspiration
Factors that increase the risk of perioperative pulmonary aspiration are as follows:
Conditions that increase gastric contents: full stomach (eating, non-fasting), emergency surgery, acute abdominal pathology, delayed gastric empting (due to neuropathy or opioid use), diabetes, ileus, and pregnancy.
Conditions that decrease the tone of the esophageal sphincter: known uncontrolled gastroesophageal reflux disease (GERD), esophageal disorder (achalasia, stricture, Zenker’s diverticulum), previous gastric banding, and gastric bypass surgery.
Conditions that depress laryngeal reflexes: brain injury, neuromuscular disorders (Parkinson’s disease, multiple sclerosis, cerebral palsy, etc).
28.8.4 Diagnosis of Aspiration Pneumonitis
Visible gastric contents in the oropharynx always warrant suspicions of aspiration. Clinical manifestation of aspiration pneumonitis could be both asymptomatic and symptomatic. Aspiration of at least 0.4 ml/kg in volume and pH of contents of <2.5 is required to produce symptoms. Classic symptoms associated with pulmonary aspiration include sudden onset of wheezing, shortness of breath (in awake patients), bronchospasm, desaturation, cyanosis, and tachycardia. The severity of bronchitis may relate to the pH and volume of the aspirated content, however, the presence of particles is most important. A chest X-ray (CXR) may be useful in diagnosing aspiration pneumonitis. However, CXR can be normal in patients with uncomplicated clinical cases. In one-third of aspiration cases, the initial CXR does not represent the full extent of lung involvement. Both the right and left lung can be affected; however, occurrence in the lower lobes is more common. CXR can show infiltrates as small, irregular opacities, confluent opacities, acinar opacities, or mixed patterns .
28.8.5 Prevention of Perioperative Pulmonary Aspiration
Prevention is the key to reduce morbidity and mortality of aspiration pneumonitis.
Patients undergoing elective surgery should be instructed to fast according to the ASA fasting guideline . A minimum fasting period for clear liquids, breast milk, infant formula/nonhuman milk, and a light meal are 2 h, 4 h, and 6 h respectively. Eight hours or more fasting time is required if a patient ingests meat, fried, or fatty foods. Both the amount and type of food must be considered when determining an appropriate fasting period.