Acute respiratory distress syndrome after administration of lidocaine in bronchoscopy

ABSTRACT

Lidocaine is the most commonly used local anaesthetic agent for bronchoscopy, and adverse reactions secondary to its use have rarely been reported. Among the possible adverse reactions, the most common is lidocaine toxicity. Secondary reactions to the use of nontoxic doses of lidocaine are infrequent, and acute respiratory distress syndrome following its administration is exceptional.

INTRODUCTION

Airway anaesthesia is a prerequisite prior to bronchoscopy, both for better patient tolerance and for the comfort of the endoscopist. Lidocaine is the most commonly used local anaesthetic in this procedure due to its relatively broad safety profile.[1,2] In this context, lidocaine can be administered in different ways: sprayed (using an atomiser to spray lidocaine into the upper airways), nebulised, applied as a gel (by placing it in the nostrils, mouth, and throat), or instilled through the bronchoscope channel.[2] Lidocaine administered via the endotracheobronchial route is rapidly absorbed, entering the systemic circulation, but maintains serum levels well below those universally considered toxic (8 mg/kg in adults).[3] Adverse reactions with lidocaine are rare and are usually related to the accidental administration of toxic doses of the drug, and in these cases, it is more frequent to affect the central nervous system and the cardiovascular system.[1,2] There are very few cases described in the literature of adult respiratory distress syndrome (ARDS) secondary to lidocaine administration. So far, only three such cases have been reported in the literature following lidocaine administration in a bronchoscopic procedure.

CASE HISTORY

A 67-year-old woman with a history of smoking, with a pack/year of 35, obesity, mild Chronic obstructive pulmonary disease (COPD), breast cancer in complete remission, and hypothyroidism on replacement therapy. She underwent a lung biopsy to evaluate a peripheral pulmonary nodule in the left lower lobe. Blood tests and an electrocardiogram were normal. Before the procedure, the patient had a blood pressure of 125/76 mmHg, a respiratory rate of 20 rpm, a heart rate of 89 bpm, and an oxygen saturation measured by pulse oximetry of 98%. Propofol perfusion at 1.5 mg/kg/h and <20 ml of topical lidocaine 2% were used during lung biopsy. No lung injury could be identified, so only bronchoalveolar lavage was performed. The patient remained stable throughout the procedure, which lasted approximately 15 min. Five minutes after the end of Flexible bronchoscopy (FB), the patient abruptly presented tachypnoea of 32 rpm, tachycardia of 134 bpm, and SatO2 of 80%. There was no jugular vein distension, and scattered wheezing was auscultated.

The results of the laboratory tests are summarised in Table 1. Bedside echocardiogram and pulmonary ultrasound showed no significant alterations; chest X-ray revealed bilateral pulmonary infiltrates [Figure 1a and b]. Two hundred milligram of hydrocortisone and short-acting bronchodilators were administered. Subsequently, orotracheal intubation was performed, and mechanical ventilation was initiated with the following parameters: tidal volume of 467 mL, respiratory rate of 16 breaths per minute, FiO₂ at 100%, positive end-expiratory pressure of 11 cmH₂O, inspiratory time of 1.0 s, I: E ratio of 1:2, inspiratory flow of 40 L/min, and flow trigger of 2 L/min. After 24 h of ventilatory support, a control arterial blood gas analysis was performed [Table 1]. During her evolution, the patient presented with difficult weaning. The first attempt at extubation failed, with the appearance of stridor and use of accessory respiratory muscles. Laryngeal oedema was suspected as the cause of the failure, which was confirmed by FB. In view of this, treatment with dexamethasone 8 mg IV every 6 h for 48 h was initiated. Subsequently, extubation was successfully achieved on the second attempt, with favourable clinical evolution [Figure 1c-e].

Table 1.

The patient’s laboratory findings

Laboratory findings	Patient’s results (Hospitalisation Day 1)	Patient’s results (Hospitalisation Day 2)	Normal values
White blood cell (WBC) (×103/µL)	10.1	10	4.5–10.8
Neutrophils (%)	67	63	40–75
Haemoglobin (g/dL)	12.5	12.2	11.8–17.8
Haematocrit (%)	38	39	37.7–47.9
Platelet count (×103/µL)	700	750	150–350
C-reactive protein (CRP) (mg/L)	22.7	14.1	<4
D-dimer (ng/mL)	127	----	0–500
Troponin I (ng/mL).	0.01	----	0–0.04
NT-proBNP (pg/mL)	35	----	0–125
pH	7.40	7.37
pCO2 (mmHg)	41	42	35–45
pO2 (mmHg)	42	56	80–100

Figure 1.

(a) Chest X-ray performed prior to FB. (b) X-ray performed after the onset of symptoms, showing an interstitial pattern. (c) Follow-up X-ray 24 h after the start of invasive mechanical ventilation. (d) Favourable radiological evolution; the image corresponds to the radiological follow-up performed on the seventh day after mechanical ventilation. Here, the first attempt at extubation is made, without success. (e) Follow-up X-ray performed on the ninth day of hospitalisation. After starting corticosteroid therapy for 48 h, a new attempt at extubation was made, which was successful

Upon discharge, the patient was referred to an allergist. She was questioned again about any history of allergies to medications and/or foods, which she denied. A skin test was performed with propofol and lidocaine, which was negative. Given these results, an intradermal test was performed, and a papule was observed only after the administration of lidocaine. Hypersensitivity to egg yolk and soy (excipients of propofol) was not studied, as the patient reported tolerance to the consumption of these foods, which allowed us to rule out allergy to the excipients of propofol. I therefore categorised it as an anaphylactoid reaction secondary to the administration of the anaesthetic. In view of this, new pulmonary infiltrates, a pO₂/FiO₂ ratio of 56, and after ruling out cardiogenic causes, the diagnosis of ARDS was confirmed after lidocaine administration according to the Berlin criteria.[3]

DISCUSSION

Lidocaine is the local anaesthetic of choice in bronchoscopic procedures and can be administered in a variety of ways: nasal fossa anaesthesia can be performed with lidocaine aerosol or gel at 2 or 4%; oropharyngeal anaesthesia is performed with lidocaine aerosol at 10% or nebulisation at 4 or 5%; and vocal cord anaesthesia can be performed with nebulisation, administration of one or several boluses of lidocaine at 2 or 5%, or transcryotid instillation.[4,5,6] The choice of lidocaine presentation will depend on whether the bronchoscopic approach is performed nasally or orally. It is recommended that during FB, the dose should not exceed 8 mg/kg in adults (29 ml of a 2% solution for a patient weighing approximately 70 kg).[7,8] When lidocaine is administered endotracheally, there are two routes of absorption: a faster one at the alveolar level and a slower one through the bronchial mucosa.[5,8] Lidocaine remains in the serum for a prolonged period of time, reaching the maximum concentration at 0.57 h after administration.[9] The percentages absorbed can range from 20% to 60% of the total dose administered; even at higher doses, serum levels are minimal.[8] This means that the drug has a wide margin of safety.

The low percentage absorbed is due to two factors: one is due to the FB technique, and the other to the physicochemical characteristics of the drug. The first is due to the fact that part of the anaesthetic administered is recovered through the bronchoscope with aspirations during the scan. The second is due to the incomplete bioavailability of the anaesthetic administered by this route.[10] Elimination of the drug occurs mainly by hepatic biotransformation, which metabolises up to 90% of the administered dose.[5,9] Therefore, renal insufficiency does not significantly affect the elimination of the anaesthetic, although hepatic insufficiency does.[9] The incidence of complications occurring during the preparation phase for FB (local anaesthesia plus premedication) is 0.09%.[1] Possible side effects after lidocaine administration are anaphylactic reaction, anaphylactoid reaction, nonallergic toxicity, and bronchospasm.[5] Anaphylactic reaction is a multisystem involvement, dependent on humoral response and requiring prior exposure to the drug. Anaphylactoid reaction is a monosystemic involvement, not dependent on humoral response, and may occur after the first administration of the drug.[6,7] Nonallergic toxicity is due to excessive dosage or impaired clearance of the drug, most often impacting the central nervous system or cardiovascular system. It commonly presents as seizures, cardiac depression, or methemoglobinemia.[5] Presentation in the form of bronchospasm is usually associated with nebulised lidocaine administration, being more frequent in patients with chronic airway disease (e.g., bronchial asthma).[5]

To date, three cases of Acute respiratory distress syndrome (ARSD) following lidocaine administration during FB have been reported.[2,3,4] In our case, it was an anaphylactoid reaction secondary to lidocaine administration, as only a papule developed in the intradermal test after exposure to the drug. Furthermore, it was the first time that lidocaine had been administered to the patient, which reinforces the hypothesis of a hypersensitivity reaction. The diffuse alveolar pattern observed on the chest X-ray could suggest aspiration pneumonia; however, there were no episodes of vomiting or fever. On the other hand, clinical, laboratory, and ultrasound findings ruled out cardiogenic or thromboembolic causes. Drug toxicity was also ruled out, as the patient had no predisposing comorbidities and no doses higher than those recommended were administered. Hypersensitivity to propofol was also ruled out; hypersensitivity to egg yolk and soy, excipients of propofol, was not studied, as it is not indicated to do so systematically, except when there is evidence or a history of allergic reactions to these compounds.[11] Regarding the first failed attempt at extubation, despite a negative air leak test, it is considered that it may have failed due to the presence of predisposing factors for laryngeal oedema, such as obesity and COPD. Both factors can alter respiratory mechanics and airway dynamics, which could have contributed to the leak test yielding a false negative, masking clinically relevant laryngeal oedema. This case highlights the rare but clinically relevant possibility of developing ARSD secondary to an anaphylactoid reaction to lidocaine during FB. Although lidocaine is a commonly used local anaesthetic with a wide safety margin, its administration can trigger serious adverse reactions, even in patients with no known prior exposure. Early recognition of this complication is essential for initiating appropriate treatment and avoiding adverse outcomes. Therefore, it is essential that clinical teams performing bronchoscopic procedures be alert to this possible reaction and have protocols in place for its immediate diagnosis and management.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.