Chemoradiation therapy for oesophageal cancer with airway stenosis under mechanical ventilation with light sedation using dexmedetomidine alone

Abstract

For malignant tumours, treatment is rarely indicated in cases requiring mechanical ventilation management because such intensive care would engender a decrease in performance status. However, light sedation using dexmedetomidine might enable chemoradiation while accommodating activities of daily living. We experienced two cases of fatal tracheal invasion and airway stenosis of stage Ⅳ oesophageal cancer that were treated with chemoradiation or radiation under mechanical ventilation (one case was differential lung ventilation.) with dexmedetomidine alone and rehabilitation was performed under a ventilator. Early mobilisation by light sedation with dexmedetomidine can inhibit performance status decline attributable to mechanical ventilation. Bridging tracheal intubation with light sedation by dexmedetomidine for temporary chemoradiation therapy to reduce tumour volume might present a good alternative for patients with malignant tumour.

Background

Malignant tumours are a chronic condition, but they sometimes cause oncological emergencies such as tumour lysis syndrome or airway obstruction with tracheal invasion, which might require emergency response and multidisciplinary treatment including ventilator management. However, ventilator management with sedation and analgesia definitely reduce performance status (PS). Therefore, chemotherapy and radiation therapy are rarely indicated for patients requiring ventilator management.¹ Light sedation and early mobilisation have recently been recommended for intensive care.² Such light sedation might be useful to minimise adverse effects on activities of daily living and to minimise PS decline under mechanical ventilation.

Dexmedetomidine (DEX), a highly selective α2 adrenergic receptor agonist with sedative and analgesic effects, is a key drug for light sedation because it enables good communication under sedation with little respiratory depression.^{3 4} The present report describes two cases of oesophageal cancer with urgent and fatal tracheal invasion. Each had a good outcome after chemoradiation therapy under mechanical ventilation.

Case presentation

Case 1

A 61-year-old man with no medical history presented to the hospital complaining of cough, slight fever and anorexia. At that time, he smoked 40 cigarettes and drank 3 L of beer each day. The patient was diagnosed with right pneumothorax and was admitted to another hospital. After admission, he had problem of frequent coughing and respiratory distress. Contrast-enhanced CT scanning revealed oesophageal cancer with tracheal invasion. He was transferred to our hospital for additional examination and treatment. Physical examination showed 170 cm height and 42.0 kg body weight (body mass index (BMI) 14.5). Blood pressure was 97/60 mm Hg, heart rate was 100/min and temperature was 38.2°C. Strider and bilateral coarse crackle were confirmed.

Case 2

A 60-year-old man with no medical history presented with problem of dysphagia. Although an ex-smoker, he had smoked 20 cigarettes a day when 20–30 years old. He consumed alcohol: about 180 mL of Japanese shochu daily (alcohol conversion: approximately 35 g/day). The patient was diagnosed with oesophageal cancer. Radical surgery was performed after preoperative chemotherapy. The pathology diagnosis was well to moderately differentiated squamous cell carcinoma (SCC). After discharge, respiratory distress was observed. An examination revealed oesophageal cancer recurring in the tracheal bifurcation. After hospitalisation, respiratory symptoms worsened. Therefore, emergency intubation was performed. He was admitted to the intensive care unit (ICU). Physical examination on admission revealed that he was of 174 cm height and 67.1 kg weight (BMI 22.2). Strider and wheeze were confirmed; the left respiratory sound was low. His body temperature was 37.0°C, with SpO₂ of 80% in room air, blood pressure of 119/82 mm Hg and heart rate of 116.

Investigations

Case 1

Blood tests under nasal cannula oxygen 2 L/min showed pH 7.45, CO₂ 44.2 mm Hg, pO₂ 90.2 mm Hg, HCO₃ 30.3, white cell count (WCC) 10.9×10⁹/L, C reactive protein (CRP) 5.0 and brain natriuretic peptide (BNP) 61.8 pg/mL. CT on admission revealed tumour lesions infiltrating the trachea and lymph node swelling (figure 1). The oesophageal cancer was clinical stage IV, T4N3M0. The pathology diagnosis was well to moderately differentiated SCC.

Figure 1.

Contrast-enhanced chest CT on admission: oesophageal cancer infiltrating the trachea.

Case 2

A blood test conducted under nasal cannula oxygen 6 L/min revealed the following: pH 7.445, pCO₂ 56.3 mm Hg, pO₂ 52.5 mm Hg, HCO₃ 38.6 mmol/L, WCC 5.5×10⁹/L and CRP 1.60 mg/dL. Tumour markers were carcinoembryonic antigen (CEA) 3.7 ng/mL, SCC 108 ng/mL and CA19-9 49 U/mL. Subsequent CT results showed a mass lesion in the tracheal bifurcation. Tracheal stenosis was found using bronchoscopy. Bronchoscopy revealed recurrence of oesophageal cancer with obstruction at the tracheal bifurcation (figure 2). Complete obstruction was also observed in the left bronchus.

Figure 2.

Bronchoscopic findings on admission. Recurrence of oesophageal cancer with obstruction at the tracheal bifurcation. Obstruction was also observed in the left bronchus: (A) tracheal bifurcation and (B) left bronchi.

Treatment

Case 1

Attempted radiotherapy failed: he was unable to maintain a supine position because of breathing difficulty. We decided to administer radiochemotherapy under intubation for upper oesophageal cancer with tracheal infiltration. Bronchoscopy revealed subcircumferential tracheal stenosis. Because a single intubation tube was not long enough to pass through the stenosis, a differential lung ventilation (DLV) tube (35 Fr for left) was intubated to release airway obstruction with a little left-sided primary bronchi infiltration. Although the DLV tube diameter was large, we could insert it carefully with preceding the bronchoscope.

A tumour mass reached the right opening of the tube. Ventilation was not possible on the right. Therefore, the left cuff was collapsed. Right lung ventilation was performed with a leak from the left. DEX alone was administered as a sedative. Radiotherapy (60 Gy/30 Fr) was started on day 5. Early rehabilitation was initiated from the second day of ICU admission. Gait rehabilitation under mechanical ventilation was started on day 11. The tube was extubated on day 17. He was discharged from the ICU. A CT scan on the day 14 after leaving the ICU revealed tracheoesophageal fistula as a side effect of radiotherapy. Radiotherapy was discontinued at 40 Gy/18 Fr.

A second course of chemotherapy was performed on day 35.

Case 2

Radiation therapy (2.0 Gy ×24 times) for mass reduction was started from the fourth day of intubation. On day 24 after intubation, the left bronchus was opened. Respiratory symptoms improved. Respiratory rehabilitation was started on the fourth day after intubation and gait rehabilitation under mechanical ventilation was started on day 25. Tracheostomy was performed on day 39 after intubation because of respiratory muscle fatigue

Outcome and follow-up

Case 1

About a month and a half after admission, the patient was discharged to return home on his own. Although the CT scan at discharge revealed progressive disease (PD) due to rib metastasis,⁵ he was discharged with preserved physical function.

Case 2

He was weaned off of ventilator and he was moved to the general ward on day 43 after entering the ICU. At ICU discharge, he preserved physical function despite the pancreatic metastasis indicating PD.⁵

Discussion

In our cases, chemoradiation therapy was performed under mechanical ventilation using light sedation with DEX for stage IV oesophageal cancer invading into the bronchus. The prognosis for stage IV oesophageal cancer is poor, with median survival of 5–6 months.⁶ Treatments for airway stenosis because of tumour invasion include stent placement, radiotherapy and laser ablation. Appropriate treatment should be selected depending on the underlying condition and stenosis, but each treatment requires advanced techniques; each carries procedure-related risk.^7–9 In these two cases, the treatment options were difficult for the following reasons: first, because the stenosis was near the tracheal bifurcation, it was difficult to place a stent under advanced stenosis. Second, chemoradiation-associated risk of perforation increases after stent placement.

In radiotherapy, maintaining a supine position is necessary, but if a high risk of airway obstruction during radiotherapy exists, then endotracheal intubation is necessary. However, for patients with a malignant tumour, it is basically PS4 at the time of intubation. It also presents a risk of ventilator-acquired pneumonia. Therefore, further treatment is difficult.^{10 11} However, light sedation might mitigate the decrease in PS, even under mechanical ventilation. From this perspective, appropriate selection of sedative and analgesic drugs that realise light sedation is important. DEX is effective for achieving light sedation and early mobilisation¹² by making the state that resembles natural sleep.¹³ Moreover, it is known that DEX has effects of suppressing delirium.¹⁴ Additionally, DEX is metabolised promptly in the liver, with half-life of only about 2–3 hours; thus, there is no prolonged effect and less respiratory depression. For these reasons, DEX is considered suitable for light sedation required for radiotherapy.

In our case 1, we were able to achieve appropriate light sedation using DEX alone under the DLV tube, while large DLV tube was not recommended to use for general tracheal stenosis. Although one case of anaesthesia during surgery performed in combination with sevoflurane inhalation has been reported,¹⁵ no report describes a study showing that DEX alone can maintain appropriate sedation and analgesia in long-term ventilation with DLV tubes. Moreover, early rehabilitation is important to maintain in-hospital function and independence.¹⁶ It would be extremely important in cases of chemoradiation for malignant tumours because PS is the most important factor for advanced treatments. Although ICU rehabilitation, especially gait rehabilitation under ventilation, requires many labour resource, it can be done safely and effectively through multiprofessional collaboration.^{16 17} Appropriate light sedation is necessary for active rehabilitation.¹⁶ From this perspective, DEX plays an important role.¹⁸

Light sedation with DEX completed chemoradiation therapy under mechanical ventilation for cases with fatal tracheal invasion of oesophageal cancer. Light sedation using DEX represents a good clinical option for patients with cancer who need critical care with tracheal intubation.

Learning points.

• We experienced two cases of fatal tracheal invasion and airway stenosis of stage Ⅳ oesophageal cancer.

• Chemoradiation or radiation under mechanical ventilation even under differential lung ventilation with dexmedetomidine alone was performed.

• Early mobilisation by light sedation with dexmedetomidine could inhibit performance status decline attributable to mechanical ventilation.

• Bridging tracheal intubation with light sedation by dexmedetomidine for temporary chemoradiation therapy to reduce tumour volume might present a good alternative for patients with malignant tumour.