Introduction
Perioperative anaphylaxis is a life-threatening condition with a mortality rate of 3%–10%.[1] Serious anaphylactic reactions during anesthesia and in the perioperative period can rapidly evolve into life-threatening situations if not recognized and managed promptly. Underreporting of such cases has led to a lack of awareness about the magnitude of this problem in India. After taking informed written consent, we present the case of a female patient posted for laparoscopic cholecystectomy who developed a severe anaphylactic response to intravenous diclofenac in the post-anesthesia care unit.
Case Presentation
After a meticulous pre-anesthetic evaluation, a 45-year-old female patient was posted for laparoscopic cholecystectomy under general anesthesia (GA). There was no significant medical and surgical history, no history of drug or food allergy, and the American Society of Anesthesiologists (ASA) grade was I. The patient was induced with injection (inj.) glycopyrrolate, inj. fentanyl, inj. propofol, and inj. atracurium intravenously (IV). Intubation was done with a 7.5-mm internal diameter endotracheal tube and anesthesia was maintained with isoflurane in a 1:1 mixture of oxygen and air. The surgery ended uneventfully after 60 minutes and the patient was extubated. After confirming adequate airway reflexes, stable hemodynamics, and respiratory parameters, the patient was shifted to the post-anesthesia care unit (PACU). In the PACU, the patient complained of pain for which inj. diclofenac 75 mg was administered slowly intravenously. Within 10 minutes of administration, the patient reported difficulty in breathing. The PACU staff in response increased the supplemental oxygen therapy from 2 L/min to 6 L/min. Even after five minutes, when the patient continued to have respiratory difficulty (maintaining SpO2 around 94%–95%), the staff informed us of the event inside the operation theater. The bilateral air entry in the chest was present but decreased. Arterial blood gas was sent for analysis and an ultrasound was arranged for evaluation of the chest. The temporal relationship with the administration of diclofenac also indicated the probable diagnosis of hypersensitivity reaction. However, there was no rash found on physical examination. Inj. pheniramine 30 mg IV and inj. hydrocortisone 100 mg IV was administered. Within the next few moments, the patient developed hypotension and bradycardia and the oxygen saturation (SpO2) began to decline. The following parameters were recorded: blood pressure at 60/30 mmHg, heart rate at 38/min, and SpO2 falling to 78%. Owing to the severe cardiovascular collapse, cardiopulmonary resuscitation (CPR) was initiated immediately, following the ACLS guidelines, and the patient's airway was secured with the endotracheal tube. Drugs including 0.5 mL of inj. Adrenaline (1 in 10,000) was administered intravenously. Intravenous fluids and inotrope support were provided. The patient showed improvement and after 30 minutes of rigorous resuscitation, her hemodynamic and respiratory parameters had stabilized. Her arterial blood gas analysis was normal. Perioperative point of care ultrasound for the presence of pneumothorax was negative. The patient was electively ventilated thereafter and extubated after three hours. A chest radiograph done six hours later was normal. Her post-surgical progress over the next two days was uneventful. The intradermal skin test was done for diclofenac six weeks after the surgery and came out positive. The Naranjo Adverse Drug Probability Score was 9, indicating a definite diclofenac-related adverse drug reaction (ADR).[2]
Based on clinical history, examination, and investigations, we formed the diagnosis of an anaphylactic reaction induced by intravenous diclofenac.
Discussion
Anaphylaxis is one of the most dreaded and severe forms of immune-mediated reactions. The incidence of drug-induced anaphylaxis is estimated to range from 0.04% to 3.1%, with a fatality rate of 0.65%.[3] Hypersensitivity is a known feature of non-steroidal anti-inflammatory drugs (NSAIDs). These are predominantly two types, namely, COX-inhibitor-related syndromes (cross-reactive) and drug-specific (probably immune-mediated reaction). The COX-inhibitor-related responses are more common and range from aspirin-exacerbated respiratory responses to urticaria and/or angioedema reactions. The immune-mediated reactions are less common, ranging from delayed-type hypersensitivity to immunoglobulin E-mediated anaphylaxis. The common drugs responsible for anaphylaxis during perioperative care include antibiotics, muscle relaxants, opioids, induction agents, latex, blood transfusion, and analgesics including diclofenac sodium, etc. Irrespective of the underlying mechanism, the symptoms are mainly caused by the release of mediators including histamine, tryptase, cysteinyl leukotrienes, Platelet Activating factor and others.[4] It is noteworthy that the symptoms of anaphylaxis can involve any organ, with the most commonly affected being the cutaneous (88% of cases), respiratory (76.1%), cardiovascular (41.9%), and gastrointestinal (12.8%) systems.[5]
The presence of respiratory distress associated with hemodynamic instability perioperatively in laparoscopic surgery can be a result of complications including gas embolism, pneumothorax, surgical emphysema, atelectasis, and anaphylaxis. Normal findings in arterial blood gas analysis, chest X-ray, and postoperative ultrasonography (USG) of the chest ruled out the diagnosis of gas embolism, atelectasis, and pneumothorax, respectively. Epinephrine has been the first and most imperative treatment for anaphylaxis; and in view of its relative safety, whenever in doubt, epinephrine should be delivered without hesitation. The allergen skin testing was positive for diclofenac. Tryptase levels is one of the most reliant tests to assess for anaphylactic reactions peaking at nearly 90–120 minutes. However, tryptase testing was not available in our institute. The scenario in our patient fulfilled the clinical criteria for the diagnosis of anaphylaxis.[6] Hence, the final diagnosis was anaphylactic reaction to intravenous diclofenac. It is recommended to monitor patients for at least 6–12 hours following an acute anaphylaxis episode.[7]
Diclofenac by itself has been considered to be a relatively safe drug and the supporting evidence in terms of patient years of experience is huge. The adverse effects are similar to other NSAIDs ranging from gastritis, peptic ulceration, and renal dysfunction. The very rare adverse effects attributed to NSAIDS, in general, include erythema multiforme, hepatitis, anaphylaxis, and urticaria which are encountered more in case of intravenous administration as compared to other approaches.
This report is a reminder that even the safest of drugs can present the deadliest complications. It is a fairly common practice to order some intramuscular or intravenous analgesics in the day-care, in-patient wards, perioperative care units, and magnetic resonance imaging (MRI) and computed tomography (CT) suites. In various centers, the nursing staff is looking after such units with a high patient-to-nurse ratio. This inadvertently increases the risk of overlooking the initial signs and symptoms of adverse drug reactions. Another important reminder from this report is to always have an emergency crash cart with emergency drugs and airway equipment available at every place where drug delivery is being done to the patients like PACU itself or day-care suites.
Conclusion
In our patient, there was a considerable time duration over which the symptoms and signs of anaphylaxis appeared (mimicking post-laparoscopy respiratory distress), hence providing us with valuable and a longer time window to assess and intervene. However, every patient may not have the same course of events and hence, the earliest recognition and prompt action can be the only deciding factor between life and death for such patients.
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Conflicts of interest
There are no conflicts of interest.
References
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