IN the perioperative period, anaphylactic reactions are often induced by the intravenous administration of muscle relaxants, antibiotics, colloids, and radiocontrast materials as well as after local contact with latex-containing materials (e.g. , gloves, catheters, airway tube) and chlorhexidine. 1,2Inhalation of toxic and highly irritant substances contained in cleaning solutions has occasionally been incriminated to produce acute bronchospasm and hypersensitization to other allergens. 3In this report, the postoperative onset of bronchospasm, hypotension, and urticaria is described and the involvement of both immune and nonimmune mechanisms is discussed. 4,5
A 43-yr-old female nurse was referred to our hospital for open resection of a 13-mm pulmonary nodule located in the right lower lobe. She had stopped smoking 4 yr previously, and her past medical history included mild urticarial reaction to penicillin, erythromycin, codeine, and aspirin. Over the previous 6 months, the use of a disinfectant compound (Synergen®; Democal AG, Villars-sur-Glâne, Switzerland) at her workplace typically produced recurrent episodes of dry cough, breathlessness, and chest tightness. Otherwise, her medical examination, laboratory results, and functional lung volumes were all within normal values.
On the day of surgery, the patient was premedicated with 7.5 mg midazolam orally, a thoracic epidural catheter was placed, and 1.5 g cefuroxime was given intravenously for antibiotic prophylaxis. After intravenous anesthesia induction with pentobarbital (400 mg), fentanyl (100 μg), and rocuronium (40 mg), the urinary bladder was catheterized, a double-lumen bronchial tube (Mallinckrodt 37-G; Carbamed, Zurich, Switzerland) was inserted, and tube positioning was confirmed by auscultation and fiberoptic bronchoscopy. Anesthesia was maintained with inhaled desflurane (2–5%), and analgesia was provided through continuous epidural administration of bupivacaine, 0.25%, and 2 μg/ml fentanyl. Under selective left lung ventilation using a semiclosed circuit, a right minithoracotomy was performed to remove a benign pulmonary mass (hamartoma). At the end of an uneventful surgical procedure, the patient was successfully extubated, being fully awake, pain-free, hemodynamically stable, and with adequate gas exchange (fig. 1; mean blood pressure, heart rate, and oxygen saturation measured by pulse oximetry).
This article is accompanied by an Editorial View. Please see: Moss J: Allergic to anesthetics. Anesthesiology 2003; 99:521-3.
After closure of the wound dressing, operating room technicians sprayed a disinfectant (Synergen®) over the surgical tables and equipment, which were located less than 2 m from the patient's face. Within the next few minutes, the patient suddenly became restless and breathing difficulties developed, which consisted of audible expiratory wheezing, increased inspiratory effort, and arterial desaturation (down to 75%). Arterial hypotension (lowest systolic value: 65 mmHg) and generalized cutaneous erythema shortly followed the onset of respiratory distress. Immediate treatment consisted of intravenous adrenaline (0.5 mg, followed by 8.10−4· kg−1· min−1) with hydrocortisone (500 mg), and spontaneous ventilation with 100% oxygen was manually assisted via an occlusive mask in a semisitting position. Neither secretions nor gastric fluid was present in her oral cavity. Fluids were rapidly infused (250 ml hydroxyethyl starch, 5%, and 750 ml crystalloids), and ipratropium and salbutamol were given by inhalation. Over the next 3 h, the skin rash disappeared and her cardiopulmonary condition dramatically improved; blood pressure and oxygen saturation measured by pulse oximetry remained stable after withdrawal of the adrenaline infusion and positive pressure airway support. Except for moderate hyperleukocytosis, laboratory results were within normal limits. A chest radiograph showed clear lung fields and a normal cardiac shadow.
Blood taken in the postanesthesia care unit revealed elevated total immunoglobulin E (IgE) levels (899 U/ml [normal: < 100 U/ml]), and radioallergosorbent testing demonstrated raised titers of specific IgE antibodies against latex (12.9 U/ml). Retrospectively, the patient acknowledged that over the previous 12 months, mild contact dermatitis had appeared on both hands after wearing surgical gloves. In the surgical ward, the nurses were informed to keep a latex-free environment and to avoid spraying the disinfectant (Synergen®) in close vicinity to the patient. The rest of the hospital stay was unremarkable. She returned home 8 days later and resumed her job 3 weeks after surgery.
Nine weeks after surgery, a skin prick test with latex produced a 9-mm wheal and a 30-mm flare at 15 min (Stallergen). This was considered a positive result, because the histamine control gave a wheal of 4 mm and no reaction was seen in two control subjects at any concentration. Further skin testing (prick and intradermal tests) was negative with all substances to which the patient was exposed into the perioperative period, namely, thiopental, midazolam, cefuroxime, penicillin, hydroxyethyl starch, methyl paraben, bupivacaine, lidocaine, rocuronium, and chlorhexidine as well as any compounds contained in the disinfectant spray (methyl-ethyl-cetone, didecyl-dimethyl-ammonium-chloride, ethanol, and isopropanol). On the basis of these results, the patient was advised to avoid specific disinfectant products and to maintain a latex-free environment at her workplace.
In our hospital, to avoid room air pollution with potentially deleterious reactive chemicals, the medical safety committee has issued guidelines for the handling of disinfectants, warning against the application of any vaporized form.
This report illustrates the postoperative acute onset of severe asthma, followed by cardiovascular collapse and skin rash after inhalation of disinfectant compounds, in a patient with the unsuspected diagnosis of latex allergy.
In connection with anesthesia, mild signs such as flushing and skin rash are rarely considered significant, because many drugs have histamine-releasing properties. Nevertheless, assessment of patients with major intraoperative anaphylaxis should include a thorough review of any previous allergic or irritative reactions, objective documentation of clinical signs and biologic response, and performance of specific allergic tests 6–8 weeks after the event.
On the basis of clinical history, skin tests, and IgE assays, latex is a frequent cause of intraoperative anaphylaxis, ranking second after neuromuscular blocking drugs. 4,5In allergic subjects, direct epidermal or mucous contact with latex-containing materials provokes IgE-mediated degranulation of mastocytes accompanied by clinical signs ranging from mild cutaneous eruption to severe cardiopulmonary disturbances. Typically, a short time delay (minutes) elapses between antigen exposure and the onset of cardiopulmonary signs in a sensitized subject.
Sensitized patients often have multiple episodes of anaphylaxis before the correct agent is clearly identified. Hospital workers are regularly exposed to latex-containing products and toxic substances (e.g. , disinfectant) that may be implicated in various allergic and irritative reactions. 1,5,6Recently, life-threatening anaphylactic reactions to chlorhexidine have also been described, particularly among patients requiring repeated invasive procedures. 2,7
In our patient, mild signs of contact dermatitis had been overlooked at the preoperative consultation and a perioperative latex-free environment was not deemed necessary. After surgery, the diagnosis of latex hypersensitivity was clearly documented by immunologic testing, although no acute symptom was elicited by direct contact with the face mask, oral airway, bronchial tube, ventilation circuit, urinary catheter, perfusion lines, or surgical gloves, which all contained latex.
A striking clinical feature was the close temporal association between a routine cleaning procedure near the extubated patient and the onset of life-threatening manifestations. Although immune hypersensitization to several reactive chemicals contained in surface disinfectant has been reported in anecdotal clinical cases, 8,9allergologic investigations were all negative for intravenous drugs, surface disinfectants (including chlorhexidine), and cleaning substances, except for latex.
Several arguments suggest that inhalation of sprayed forms of disinfectant products could trigger the observed sequence of respiratory, cardiovascular, and cutaneous abnormalities. First, clinical history confirmed the hyperreactivity of the patient's airway to the same disinfectant, characterized by dry cough and dyspnea 10; high airway concentrations of water-soluble substances like quaternary amines (didecyl-dimethyl-ammonium-chloride) contained in most disinfectants are known to induce reversible upper airways constriction in susceptible subjects, a so-called reactive airway dysfunction syndrome. 11Second, chronic or repeated exposure to nonallergenic and irritant substances included in disinfectants has been shown to enhance IgE sensitization to common allergens (e.g. , latex) and has been identified as a risk factor for atopy and airway constriction. 12Third, didecyl-dimethyl-ammonium-chloride is a polycationic agent whose interaction with membrane surface receptors has been shown to potentiate the release of IgE-dependent histamine from mastocytes and therefore to amplify the acute response to immunogenic agents. 13Fourth, the release of inflammatory mediators (e.g. , cytokines, prostanoids) as a result of surgical manipulation, ischemia–reperfusion injury, and stress failure of the alveolar–capillary barrier could also amplify the anaphylactic response and its clinical manifestations. 14
Taken together, these data suggest that “silent” hypersensitivity to latex could possibly be aggravated or unmasked by concomitant airway challenge with quaternary amines acting as coallergens in the context of surgical stress, airway instrumentation, and one-lung ventilation. Although intraoperative exposure to multiple latex-containing products failed to provoke an immediate allergic reaction, inhalation of disinfec-tant substances shortly after tracheal extubation was associated with the development of the full scale of acute respiratory, hemodynamic, and cutaneous manifestations.