A 62-year-old woman undergoes hip replacement surgery. The patient has a history of advanced hip osteoarthritis that limits her daily activities. She has no other medical conditions and no known drug allergies. After appropriate preoperative evaluation, total hip arthroplasty is performed under general anesthesia. The intraoperative course is uncomplicated, and after recovery from anesthesia, patient-controlled intravenous morphine is started for pain control. Several minutes later, the patient reports generalized itching. Physical examination reveals hypotension, tachycardia, and mild bilateral wheezing but no rashes. Which of the following drug effects is most likely responsible for this patient's current condition?

Question

A 62-year-old woman undergoes hip replacement surgery.  The patient has a history of advanced hip osteoarthritis that limits her daily activities.  She has no other medical conditions and no known drug allergies.  After appropriate preoperative evaluation, total hip arthroplasty is performed under general anesthesia.  The intraoperative course is uncomplicated, and after recovery from anesthesia, patient-controlled intravenous morphine is started for pain control.  Several minutes later, the patient reports generalized itching.  Physical examination reveals hypotension, tachycardia, and mild bilateral wheezing but no rashes.  Which of the following drug effects is most likely responsible for this patient's current condition?

Quizplus · Accepted Answer

Opioids (eg, morphine) can generate a pseudoallergic response by directly stimulating mast cell degranulation, releasing histamine and other vasoactive mediators. This nonimmunologic reaction can cause itching, urticarial rash, wheezing, hypotension, and tachycardia that closely mimic true IgE-mediated type 1 hypersensitivity (eg, anaphylaxis). However, true IgE-mediated allergic reaction is rare with opioids (Choice D), and suggestive symptoms rarely indicate the need to avoid opioids altogether. Because direct mast cell degranulation tends to be most prominent with relatively low-potency opioids (eg, morphine, meperidine), a relatively high-potency opioid (eg, fentanyl) is usually better tolerated. Other drugs that can have a similar non-IgE-mediated effect on mast cell degranulation include vancomycin (ie, red man syndrome) and radioiodine contrast. (Choice A) Halothane, an inhalation anesthetic, is rarely used but can cause hypotension via direct suppression of myocardial contractility. It is not associated with itching and wheezing. (Choice B) Because pain increases sympathetic output, opioid analgesia can reduce sympathetic output and thus decrease heart rate and blood pressure. However, this does not explain the itching and wheezing. (Choice E) Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase, which leads to increased 5-lipoxygenase activity. This effect can precipitate bronchoconstriction and wheezing due to increased production of leukotrienes (ie, NSAID-exacerbated respiratory disease); however, itching and hypotension are not expected. Educational objective: Opioids (eg, morphine) can generate a pseudoallergic response by directly activating mast cells to stimulate degranulation, releasing histamine and other vasoactive mediators. This nonimmunologic reaction can cause itching, urticarial rash, wheezing, hypotension, and tachycardia that closely mimic true IgE-mediated type 1 hypersensitivity. However, true IgE-mediated allergic reaction is rare with opioids. __________ References: Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms. (http://www.ncbi.nlm.nih.gov/pubmed/29136631)

A 62-Year-Old Woman Undergoes Hip Replacement Surgery