Perioperative patient safety

1

Review the four types of hypersensitivity reactions and their mechanisms

See Table 12.1 .

2

What is an anaphylactoid reaction?

Anaphylactoid reactions clinicaly resemble allergic reactions (e.g., both involve histamine release) but are not immunoglobulin (Ig)E-mediated. Anaphylactoid reactions may present as a severe anaphylactic reaction (i.e., bronchospasm or hypotension), but generally causes more mild reactions (e.g., rash). Red man syndrome caused by vancomycin or pruritis because of morphine are examples of common anaphylactoid reactions.

3

What is the incidence of severe perioperative anaphylactic reactions?

The overall incidence is approximately one in 10,000.

4

Describe the clinical presentation of anaphylaxis

Anaphylaxis can be IgE or non-IgE–mediated with the following signs and symptoms:

• Hypotension

• Dysrhythmias

• Cardiac arrest

• Bronchospasm

• Cutaneous symptoms, including flushing, urticaria, and angioedema

• Gastrointestinal symptoms, including abdominal pain, nausea, vomiting, and diarrhea

5

What is the most common initial presentation for perioperative anaphylaxis? Is rash frequently present with severe reactions?

The presentation of anaphylaxis is a spectrum ranging from minor cutaneous signs and symptoms (more common) to hemodynamic instability and cardiac arrest (less common). In severe anaphylactic reactions, the most common presentation is hypotension followed by bronchospasm. Cutaneous signs and symptoms are a late finding in severe reactions that often are not present until after the patient is stabilized. Anaphylactic reactions are often a clinical diagnosis and can be IgE-mediated (allergic) or non-IgE–mediated (anaphylactoid), with the former generally presenting as severe reactions and the latter as minor reactions.

6

What are the most common causes of severe perioperative anaphylaxis?

• Antibiotics

• Neuromuscular blocking agents

• Chlorhexidine

• Latex

• Blue dyes

A recent study found antibiotics to be the most common cause of anaphylaxis, with neuromuscular blocking agents a close second. This is contrary to previous studies which found neuromuscular blocking agents to be the most common cause of anaphylaxis. Differences between studies are likely related to medication selection or availability and patient population differences. For example, pholcodine is an over-the-counter cough suppressant available in countries which are associated with a higher incidence of allergy to neuromuscular blocking agents but is rarely prescribed in the United States. Overall, taking various studies in aggregate, the majority of severe anaphylactic reactions seem to be attributed to antibiotics and neuromuscular blocking agents.

7

Which specific antibiotics and neuromuscular agents seem to cause the majority of severe anaphylactic reactions?

• Glycopeptide (e.g., vancomycin) antibiotics, particularly when given to patients with a history of penicillin allergy and penicillin family antibiotics (e.g., amoxicillin, piperacillin)

• Succinylcholine and rocuronium cause the majority of severe anaphylactic reactions for neuromuscular blocking agents. Succinylcholine typically presents as bronchospasm, whereas most other agents, including antibiotics, present as hypotension

8

What are the less common causes of perioperative anaphylactic reactions?

• Propofol: A rare allergy. Although propofol includes egg yolk derived lecithin and soybean oil in the emulsion, there is no evidence to suggest that patients with egg or soy allergies have increased risk of an allergic reaction to propofol. Most egg allergies are caused by the egg white proteins ovalbumin and ovomucoid, which are not contained in the propofol emulsion

• Protamine: An increasingly uncommon allergy with the advent of recombinant protamine. Risk factors include previous exposure to protamine itself or similar medications, such as Neutral Protamine Hagedorn insulin, fish allergies, or vasectomy. Protamine was historically made from salmon sperm and with the increasing use of recombinant protamine, these latter risk factors will likely abate

• Local anesthetics: Allergies to local anesthetics with amide linkages (e.g., bupivacaine, lidocaine, mepivacaine, ropivacaine) are extremely rare. Allergic reactions to local anesthetics with ester linkages (e.g., procaine, chloroprocaine, tetracaine, benzocaine), while more common than amide local anesthetics, are also rare. Allergic reactions to ester local anesthetics are predominately caused by paraaminobenzoic acid (PABA), a metabolite. Methylparaben, a preservative in amide local anesthetics, may cause allergic reactions because its chemical structure is similar to PABA. Therefore preservative-free amide local anesthetics should be used for patients at risk for local anesthetic allergies.

9

Review the issues concerning allergic reactions to neuromuscular blockers

IgE immunoglobulins are sensitive to the tertiary or quaternary ammonium groups found in neuromuscular blocking agents. Because these chemical groups are commonly found in foods, cosmetics, and over-the-counter medications, patients may have an anaphylactic reaction to neuromuscular blockers on their initial exposure. When administered rapidly, succinylcholine and some nondepolarizing neuromuscular blocking agents (i.e., atracurium and mivacurium) may cause a mild anaphylactoid reaction resulting in erythema of the chest and face, a mild drop in blood pressure, and a mild increase in heart rate. Steroidal agents (e.g., rocuronium and vecuronium) and cis-atracurium, specifically, are not associated with anaphylactoid reactions even when rapidly administered.

10

Can a patient with a penicillin allergy receive cephalosporin antibiotics?

Current evidence suggests that it is likely safe to administer cephalosporins to penicillin-allergic patients, provided the reaction was not a true “allergic” IgE-mediated anaphylactic reaction and the reaction was greater than 10 years ago. Although penicillin is one of the most commonly reported allergies, fewer than 1% of the general population has a true IgE-mediated allergy to penicillin. Most reported reactions, such as gastrointestinal symptoms or nonspecific rashes, are incorrectly labeled penicillin allergy. An anaphylactic reaction requires at least two symptoms and rash alone is not sufficient. Further, 80% of patients with a known IgE-mediated penicillin allergy will lose their sensitivity after 10 years.

An oft-quoted statistic is that there is a 10% risk of cross-sensitivity between penicillin and cephalosporins, but this is now disputed. Previously, this may have been true, possibly because early generations of cephalosporins may have contained trace amounts of penicillin from contamination during manufacturing. More recent studies show the cross-reactivity between penicillin and cephalosporins is less than 1% to 5% depending upon the generation (higher cross-reactivity with first and second generation and lower cross-reactivity with higher generation cephalosporins).

Therefore patients with a remote history of penicillin allergy causing only a rash and no other signs or symptoms suggesting anaphylaxis may be a candidate for cephalosporin antibiotics, especially if the reported allergic reaction was greater than 10 years ago. Clinical judgement is warranted in these situations with an assessment of the benefit/risk in administrating cephalosporin antibiotics versus alternative agents, which may be more expensive, less efficacious, and carry their own risk of anaphylaxis as well.

11

What are the risk factors for a latex allergy?

• Congenital spinal cord abnormalities (e.g., spina bifida)

• Multiple prior surgical operations

• High occupational exposure to latex (e.g., healthcare workers)

• Atopic individuals (e.g., eczema, asthma, allergic rhinitis)

• Sensitivity to specific foods (e.g., avocado, banana, kiwi, chestnut, papaya, white potato, tomato)

12

How should an operating room (OR) be prepared for a latex-allergic patient?

Surgical operations for latex-allergic patients ideally should be scheduled first case of the day, because the quantity of airborne latex particles will be minimized. Use only nonlatex surgical and anesthesia supplies, including nonlatex gloves. Increasingly, latex-free medical supplies are becoming the standard for all patients, but it is important to be familiar with your hospital’s equipment.

13

How should severe anaphylaxis be treated?

• Epinephrine, either 0.5 mg intramuscular (IM) or 10 to 500 mcg intravenous (IV) depending on severity, patient response, and if the patient is well-monitored (IV) or not well-monitored (IM). IM is more hemodynamically stable and has a longer duration of action but IV has a more rapid onset. Patients frequently require multiple re-doses and some, an epinephrine infusion

• Aggressive volume resuscitation (i.e., bolus 1–2 L of crystalloid repeated as necessary)

• Initiate cardiopulmonary resuscitation if no pulse detected for more than 10 seconds, or systolic blood pressure less than 50 mm Hg

• Administer 100% oxygen to minimize hypoxemia during bronchospasm

• Consider albuterol for bronchospasm. Note, in severe bronchospasm, albuterol may not be adequately delivered to bronchospastic airways and treatment will require IV epinephrine for β-2 mediated bronchodilation

• Consider vasopressin 1 to 2 unit bolus

• Consider intubation for airway edema

• There is no high-quality evidence to support or refute the use of antihistamines (agents with H ₁ (e.g., famotidine) or H ₂ antagonism (e.g., diphenhydramine) or corticosteroids in the acute management of anaphylaxis)

• Consider admitting the patient for observation of rebound anaphylaxis (4–12 hours after the initial event)

14

Why is epinephrine the first-line agent for anaphylaxis? How does it work?

Epinephrine in the most important therapy for anaphylaxis for several reasons. First, it is readily available in most hospitals and has a rapid onset of action. It can be administered in almost every way possible such as IV, endotracheal, subcutaneous, intraosseous, and IM (most common route in the emergency department or outside of the hospital). Second, it stabilizes mast cells preventing further histamine release. Third, it directly treats the pathophysiology of anaphylaxis: (1) β-1 agonism increases cardiac contractility, (2) β-2 agonism causes bronchodilation, and (3) α-1 agonism increases systemic vascular resistance, increases venous return, and may reduce bronchial secretions.

15

How do you manage anaphylaxis for a patient taking beta-blockers?

Glucagon. If not readily available, give epinephrine at higher doses.

16

Should patients with a prior history of allergic reaction be pretreated with histamine blockers or corticosteroids?

Although premedication with corticosteroids and antihistamines is not uncommon in some settings, such as before IV contrast, chemotherapy, and some immunosuppressant infusions, there is no specific evidence that favors premedication during the perioperative phase as a means of preventing anaphylaxis.

17

How do you distinguish a perioperative allergic reaction from a nonallergic event? Why is it important to make this distinction?

Check a serum tryptase level immediately once the patient is stabilized. Serum tryptase levels peak within 15 and 120 minutes after the onset of an IgE-mediated anaphylactic reaction and have a half-life of about 120 minutes.

After a suspected intraoperative allergic reaction, a patient should be referred to an allergist/immunologist for evaluation and prescribed an “epi pen.” Detailed reporting of the episode and a serum tryptase level can assist the allergist in distinguishing between an IgE or non-IgE–mediated anaphylactic reaction. However, a positive tryptase does not specify the responsible antigen and only confirms the reaction was IgE-mediated. Often, there are other confounding antigens, such as chlorhexidine and latex, that could also cause anaphylactic reactions in addition to administered medications. If the tryptase is positive, the allergist should perform skin testing for all common antigens exposed to the patient in the perioperative period to confirm the responsible antigen.