Combined esketamine and dexmedetomidine for awake tracheal intubation in a patient with a difficult airway due to a giant lingual vascular malformation: a case report

Introduction

Vascular malformations are congenital disorders primarily caused by abnormal activation of signaling pathways due to genetic mutations. These lesions frequently occur in the head and neck region, accounting for approximately 40% of cases, and often worsen with age, leading to pain, bleeding, cosmetic deformities, and functional impairments. Magnetic resonance imaging (MRI) serves as the gold standard for assessing lesion extent and hemodynamic characteristics. Treatment strategies now emphasize a multidisciplinary and individualized approach, including surgical resection, sclerotherapy, and laser intervention, with significant recent advancements also achieved through the application of targeted drug therapies.

Patients with oral vascular malformations are frequently complicated by difficult airways, particularly when lesions involve the maxillofacial region, tongue base, or pharynx, which can readily lead to anatomical distortion or obstruction of the airway. For known or suspected difficult airways, international guidelines recommend a strategy of awake tracheal intubation with preserved spontaneous breathing, prioritizing the use of visualization technologies such as fiberoptic bronchoscopy to avoid blind instrumentation.

However, massive lingual vascular malformations present unique and severe challenges for such procedures. These lesions are highly vascularized and structurally fragile, meaning that any induced coughing, gagging, or movement can trigger bleeding. This can rapidly obscure the fiberoptic bronchoscope’s view and even lead to catastrophic airway obstruction. Traditional sedation regimens, such as benzodiazepines alone or high-dose opioids, while providing sedation and analgesia, carry significant risks, including respiratory drive depression, excessive blunting of airway reflexes, and opioid-induced chest wall rigidity. In these scenarios, respiratory depression may force the anesthesiologist to intervene emergently, paradoxically increasing the difficulty of airway manipulation and the risk of bleeding. Therefore, the ideal sedation protocol must provide adequate sedation, analgesia, and amnesia while maximizing the preservation of spontaneous breathing and protective airway reflexes, and ideally possessing intrinsic respiratory stimulant properties. Based on these requirements, the combination of dexmedetomidine and a ketamine-class drug appears theoretically advantageous. Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, produces a “cooperative sedation” resembling natural sleep with minimal impact on respiratory function. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, provides potent analgesia and dissociative anesthesia while stimulating the sympathetic nervous system to maintain or even enhance respiratory drive. The combination of the two may produce a synergistic effect, achieving a balance of sedation, analgesia, and respiratory stability. In this case report, we selected esketamine, the S(+)-enantiomer of ketamine. Compared to racemic ketamine, esketamine has approximately twice the affinity for the NMDA receptor, meaning a lower dose is required for equivalent analgesic effect. More importantly, available evidence suggests that esketamine may possess a more favorable pharmacokinetic profile, with faster onset and more rapid recovery, and potentially a lower incidence of psychotomimetic side effects (e.g., hallucinations, agitation). For awake intubation procedures requiring a high degree of patient cooperation, quicker awakening and fewer psychiatric side effects can improve patient tolerance and satisfaction. Therefore, we hypothesized that the combined use of esketamine and dexmedetomidine might be particularly suitable for managing difficult airways like massive lingual vascular malformations, where exceptional demands are placed on respiratory stability and procedural smoothness. This case provides the first detailed description of the feasibility and potential advantages of combining esketamine and dexmedetomidine for awake intubation in this specific high-risk patient population (1). We present this article in accordance with the CARE reporting checklist (available at https://joma.amegroups.com/article/view/10.21037/joma-2025-1-33/rc).

Case presentation

The patient, a 57-year-old female, weighed 40 kg with a height of 150 cm (body mass index 17.8 kg/m²). Since birth, she had presented with tongue swelling and multiple bluish-purple lesions on the oral mucosa, which had persisted and slowly enlarged over time without any prior treatment. Six months prior, the patient developed an ulcer on the margin of the tongue accompanied by pain, which showed no significant improvement after oral antibiotics and topical herbal preparation. Subsequently, a papillary hyperplastic mass was observed 1 cm posterior to the left tongue ulcer. The patient denied any history of hypertension, diabetes, coronary heart disease, infectious diseases, or trauma. Physical examination revealed no significant abnormalities on cardiopulmonary auscultation. The maxillofacial region was generally symmetrical, with extensive swelling of the tongue and bluish-purple discoloration of the surface mucosa (Figure 1). The tongue texture was soft with ill-defined borders. The patient exhibited unclear speech but no choking or dyspnea. Auxiliary examinations showed no notable abnormalities in laboratory tests. Electrocardiogram and chest computed tomography (CT) were unremarkable. Enhanced CT of the maxillofacial region indicated multiple soft tissue lesions in the cervicopharyngeal, lingual, and maxillofacial regions, suggestive of venous malformation with possible phleboliths. MRI of the left tongue lesion was recommended for further evaluation. Plain MRI of the maxillofacial region (Figure 2) revealed multiple venous malformations in the cervicopharyngeal and maxillofacial areas, with abnormal signals in the left tongue, for which biopsy was advised. Otolaryngological endoscopic examination showed extensive purplish-red protruding masses in the oral cavity and pharynx, more pronounced on the right side, involving the tongue, anterior and posterior surfaces of the soft palate, tongue base, lingual and posterior surfaces of the epiglottis, right lateral pharyngeal wall, and right arytenoid. Bilateral vocal cords appeared normal with adequate mobility (Figure 3). Airway assessment indicated a mouth opening of three fingerbreadths, Mallampati class III, good head and neck mobility, and a thyromental distance of 6 cm. The preoperative diagnosis was “tongue mass, suspicious for malignancy; orofacial venous vascular malformation”, and the planned procedure was “left tongue mass excision + partial lingual venous malformation resection” under general anesthesia. Due to evident supraglottic airway difficulty, awake nasotracheal intubation under sedation, analgesia, and topical anesthesia was selected. Additionally, a contingency plan for tracheostomy was discussed with the surgical team in case of failed intubation attempts.

Figure 1 Photograph of the patient’s tongue showing the vascular malformation.

Figure 2 Representative non-contrast maxillofacial MRI from the patient. ARF, anterior right foot; FRP, foot right posterior; HLA, head left anterior; MRI, magnetic resonance imaging; PLH, posterior left head.

Figure 3 Representative laryngoscopic view from the patient.

Upon entering the operating room, the patient was placed in a supine position. An intravenous line was established in the upper limb, and sodium acetate Ringer’s solution was administered intravenously. Standard monitors were applied, showing heart rate (HR) of 89 beats/min, blood pressure (BP) of 127/65 mmHg, peripheral oxygen saturation (SpO₂) of 98%, and respiratory rate (RR) of 16 breaths/min without significant respiratory distress. The patient received oxygen via a face mask at a flow rate of 6 L/min. Approximately 10 minutes prior to intubation, an infusion of dexmedetomidine (1 µg/kg) was initiated. A 5-mL syringe was used to draw up 3 mL of 2% lidocaine. Ten minutes later, with the cricothyroid membrane as the puncture site, a distinct loss of resistance was felt upon needle insertion. After confirming free aspiration of air, the patient was instructed to hold their breath. Lidocaine was injected into the airway, and the patient was then asked to cough to facilitate even distribution of the local anesthetic. Following intravenous administration of 40 mg esketamine, the patient’s Ramsay Sedation Score was assessed to be 3. The right nostril, which demonstrated adequate patency, was selected. Fuma nasal drops were instilled in two separate applications, 3 drops each time. A nasopharyngeal airway coated with lidocaine gel was then gently inserted to a depth of approximately 15 cm. If resistance was encountered, the procedure was repeated using the other nostril. Subsequently, 2% lidocaine spray was administered through the nasopharyngeal airway, applying 2 puffs per spray for a total of 5 sprays along the path from the nostril to the glottis. After ensuring adequate topical anesthesia and reapplying the oxygen face mask, a flexible fiberoptic bronchoscope was inserted vertically through the right nostril. It was advanced through the nasal passage into the oropharynx, successfully reaching the glottic opening. The vocal cords were visualized, and the scope was gently advanced through the glottis into the trachea, where the tracheal rings and carina were identified. A 6.5-mm endotracheal tube, pre-loaded onto the bronchoscope, was then threaded into the trachea. Its position was confirmed via the bronchoscope, and the tube was secured at 26 cm at the lips. The entire procedure was completed smoothly in 10 minutes, with the patient demonstrating effective sedation and analgesia, and no coughing reflex. General anesthesia was then induced immediately with intravenous midazolam 2 mg, alfentanil 1.5 mg, propofol 80 mg, and rocuronium 40 mg. The endotracheal tube was connected to the breathing circuit, and the ventilator was set to volume control mode with a tidal volume of 320 mL and an RR of 12 breaths/min. A continuous end-tidal carbon dioxide waveform was observed, and bilateral equal and clear breath sounds were confirmed by auscultation. Anesthesia was maintained with combined intravenous and inhalational agents: 1.5–2% sevoflurane, alongside continuous infusions of propofol (5 mg·kg⁻¹·h⁻¹) and remifentanil (0.08 µg·kg⁻¹·min⁻¹). During surgery, the lesion and the underlying deep tongue muscle were completely resected and sent for pathological examination. Intraoperative frozen section analysis of the “left tongue” specimen revealed malformed vasculature and well-differentiated squamous epithelial nests beneath the mucosal epithelium, with extensive infiltration of acute and chronic inflammatory cells. A diagnosis of vascular malformation was primarily considered, and all resection margins were reported free of tumor. Adjacent soft tissue flaps were mobilized and transposed to repair and suture the surgical defect. The total surgical duration was 1 hour and 15 minutes, with an estimated blood loss of 300 mL. Intravenous fluid administration consisted of 600 mL of crystalloid and 500 mL of colloid. Hemodynamics remained stable throughout the procedure: HR 80–90 beats/min, BP 90–110/50–60 mmHg, RR 12–13 breaths/min (ventilator-controlled), and SpO₂ 100%. The patient regained consciousness 30 minutes after the conclusion of surgery. Due to the proximity of the surgical site to the airway and the risk of postoperative bleeding causing airway obstruction, the patient was transferred to the intensive care unit (ICU) with the endotracheal tube in place. The tracheal tube was safely removed on the third postoperative day in the ICU. The patient was subsequently transferred back to the general ward and was discharged without further complications. The timeline of the procedure is shown in Figure 4. Perioperative vital signs are shown in Table 1.

Figure 4 Timeline of anesthetic management and key procedural events. ICU, intensive care unit; IV, intravenous; OR, operating room.

Ethics

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Airway challenges and intubation strategy selection in giant lingual vascular malformation

Giant lingual vascular malformations, particularly the extensive venous malformation in this case involving the tongue base, epiglottis, and lateral pharyngeal wall, constitute an extremely challenging difficult airway. The risk is twofold: on one hand, the massive tongue is highly prone to posterior displacement after loss of consciousness, leading to complete upper airway obstruction; on the other hand, the lesion is highly vascular and has fragile tissue. Any direct laryngoscopy or intense airway reflexes (such as coughing or gagging) may trigger catastrophic hemorrhage (1), rapidly flooding the airway and obscuring the view. Therefore, traditional rapid sequence induction or direct laryngoscopic intubation carries extremely high risks in such patients. The 2022 American Society of Anesthesiologists (ASA) Difficult Airway Management Practice Guidelines explicitly recommend that for patients with a risk of supraglottic obstruction and anticipated difficult mask ventilation, priority should be given to awake tracheal intubation techniques under sedation and analgesia while preserving spontaneous respiration. Fiberoptic bronchoscopy, due to its visualization and ability to bypass the obstruction, is considered the gold standard in such scenarios (2,3).

Pharmacological advantages of the esketamine-dexmedetomidine combination: beyond basic sedation

However, the key to successfully performing awake fiberoptic intubation lies in finding a balance: providing sufficient sedation, analgesia, and amnesia to ensure patient tolerance and cooperation, while maximizing the preservation of spontaneous respiration, protective airway reflexes, and hemodynamic stability. The combination of esketamine and dexmedetomidine used in this case is precisely based on this careful consideration.

Dexmedetomidine, through highly selective activation of α2-adrenergic receptors (4), produces a unique “cooperative sedation”. Patients can rest quietly without stimulation and can be easily awakened to cooperate clearly, with minimal respiratory depression. However, its analgesic efficacy is limited when used alone (5), and it may cause dose-related bradycardia and hypotension.

Esketamine, the dextrorotatory isomer of ketamine, produces potent analgesia and a dissociative anesthetic state by antagonizing NMDA receptors (6). Its key advantages lie in its ability to significantly enhance respiratory drive, maintain upper airway muscle tone, and support BP and HR through sympathomimetic effects (6,7). This precisely compensates for the potential shortcomings of dexmedetomidine in analgesia and cardiovascular depression.

The synergistic effects of the two drugs were manifested in this case as follows

• Optimization of respiration and airway protection: the inherent respiratory stimulant effect of esketamine was modulated by the steady sedative properties of dexmedetomidine, achieving maintenance of spontaneous respiration under deep sedation. The potent inhibitory effect of dexmedetomidine on airway reflexes and secretions (8) likely effectively counteracted the theoretically increased salivation potentially caused by esketamine, providing a clear field of view for the bronchoscope, which was confirmed during the procedure in this case.
• Mutual hemodynamic stabilization: the potential HR reduction induced by dexmedetomidine was antagonized by the sympathomimetic effect of esketamine, thereby maintaining HR stability during intubation. This inherent complementarity reduced the need for additional vasoactive drugs.
• Sedation tailored for high bleeding risk: compared to traditional regimens based on remifentanil, this combination completely avoids the risks associated with opioids, such as respiratory depression, chest wall rigidity, and excessive suppression of the cough reflex. Preserving spontaneous respiration and appropriate airway reflexes is crucial for preventing rupture of the malformed vessels induced by positive pressure ventilation or coughing.

Dialogue with current guidelines and considerations for the protocol

Although the ASA 2022 guidelines strongly recommend awake intubation for high-risk patients, they do not provide a unified recommendation for specific sedation protocols, stating that choices should be individualized based on patient condition, operator experience, and drug characteristics (2). This case report provides a concrete example of a drug combination protocol. This protocol directly addresses the highest priority principle in the guidelines regarding “maintaining ventilation and oxygenation”. By selecting the drug combination with the least impact on respiration, it provides an additional safety buffer for managing the high-risk “cannot intubate, cannot ventilate” scenario. Furthermore, the use of esketamine in this protocol, compared to ketamine, may allow for a smaller dose due to its higher receptor affinity. Existing evidence also suggests its incidence of psychotomimetic adverse effects may be lower, which could improve patient acceptance of the awake intubation procedure and recovery quality, aligning with the guideline’s spirit of “optimizing patient comfort and experience”.

Limitations of this case

As a single case report, this study has several limitations. First and foremost, its findings cannot be extrapolated to establish general safety or efficacy; the conclusions are limited to describing the successful application in this specific case. Second, the use of “Fuma Nasal Drops” (containing ephedrine hydrochloride) during the procedure introduces a potential confounding factor. As a potent adrenergic receptor agonist, its systemic absorption may have contributed synergistically to the intraoperative hemodynamic stability, complicating the isolated evaluation of the esketamine-dexmedetomidine combination’s effect on circulation. Additionally, the assessment of sedation depth (e.g., using the Ramsay score) has a degree of subjectivity. Finally, the success of this protocol was highly dependent on adequate upper airway topical anesthesia; both components were indispensable. Future research should involve prospective clinical trials with larger sample sizes, directly comparing this protocol with other sedation regimens to more rigorously evaluate its advantages and risks in patients with similar difficult airways.

Conclusions

In summary, for this patient with a giant lingual vascular malformation and a difficult airway, successful awake nasotracheal fiberoptic intubation was achieved with the assistance of a sedation-analgesia regimen combining esketamine and dexmedetomidine, following comprehensive topical anesthesia of the airway. This drug combination demonstrated the potential to provide adequate sedation and analgesia while exceptionally preserving spontaneous respiration and stabilizing hemodynamics. Their complementary pharmacological profiles suggest that this regimen may be particularly suitable for managing difficult airways associated with a high risk of bleeding and airway obstruction. Although this study is only a single case report, it offers a potentially viable new approach for managing such extremely challenging anesthetic scenarios. Ultimately, the management of difficult airways must strictly adhere to guideline principles, emphasizing preoperative multidimensional assessment, formulation of detailed backup plans, and always prioritizing patient safety (1).

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://joma.amegroups.com/article/view/10.21037/joma-2025-1-33/rc

Peer Review File: Available at https://joma.amegroups.com/article/view/10.21037/joma-2025-1-33/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://joma.amegroups.com/article/view/10.21037/joma-2025-1-33/coif). H.J. serves as the Editor-in-Chief of Journal of Oral and Maxillofacial Anesthesia. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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