A 68-year-old male was found on CT to have a right lung nodule and paratracheal lymphadenopathy. He was then scheduled for diagnostic bronchoscopy and mediastinoscopy.

Twenty years ago, he was diagnosed with carcinoma of the right submandibular gland, and underwent excision of the gland, right radical neck dissection, and a course of radiotherapy. He quit smoking several years ago and has had hypertension for about 5 years. He has had a nonproductive cough for several months. His only medication is metoprolol.

On examination, he is in no distress at rest. His vital signs are: blood pressure 140/90, heart rate 70, and respiratory rate 18. Oxygen saturation on room air is 96%. His weight is 94 kg and he is 170 cm tall. Auscultation of the chest reveals decreased breath sounds bilaterally but no rales or rhonchi, and normal heart sounds. No carotid bruits are evident.

Airway examination reveals a Mallampati IV classification. Mouth opening is 2.5 cm and mandibular protrusion is less than 1 cm. Full upper dentition is present but the mandible is edentulous. The thyromental distance is normal. Cervical spine extension is decreased. Palpation of the submandibular tissues reveals a woody, indurated consistency. On inspection, telangiectasia and pallor of the submandibular skin are noted. The right neck has the typical appearance of a previous neck dissection. The mucosa of the tongue appears dry.

Laboratory data reveal normal electrolytes and a hemoglobin of 140 g·L⁻¹. EKG reveals nonspecific ST and T changes.

Is This Patient Fit for Anesthesia?

The patient has hypertension which is adequately controlled for his surgical procedure. Carcinoma of the lung is suspected on diagnostic imaging. He does not require further medical optimization.

What Anesthetic Technique Is Required?

General anesthesia with endotracheal intubation is required for a brief but stimulating surgical procedure.

What Anatomic and Pathophysiologic Changes Occur Following Radiotherapy to the Structures of the Oral Cavity and Neck?

Radiotherapy inflicts a radiochemical injury to both normal and malignant cells.¹ The damage is related to the total radiation dose and the method of radiotherapy delivery. In order to achieve adequate tumor control, damage to normal tissues is inevitable.^1–3 Radiation also activates various cellular signaling pathways that lead to activation of proinflammatory and profibrotic cytokines, vascular injury, and activation of the coagulation cascade.⁴ Early (acute) tissue toxicities from radiotherapy are arbitrarily considered to occur within 90 days of the commencement of treatment, and late effects beyond 90 days of treatment.^2,5 Early side effects are observed shortly after a course of radiotherapy, whereas late effects are manifest after a latent period and may not be evident until years following the radiotherapy.^2,6 In general, tissues with rapidly dividing cell populations such as mucous membranes and skin demonstrate acute effects of radiation (mucositis, desquamation), whereas those with slowly proliferating cells such as organ parenchyma, connective, and vascular tissues demonstrate late effects.^2,7 Interactions between acute and chronic reactions can occur resulting in “consequential late effects” due to loss of protective barrier function in the acute phase resulting in secondary tissue injury.² The severity of the late effects of radiation therapy in general cannot be predicted by the severity of the acute effects.⁷ Late radiation sequelae are usually irreversible and progressive, with the severity increasing with time.² Progression of late effects have been reported up to 34 years after therapy.⁴ The pathogenesis of late radiation effects are based on complex pathophysiological processes which include radiation-induced change in parenchymal cells (cell death), fibroblasts (differentiation), and vascular endothelial cells (loss of capillaries).² All of these cells and macrophages interact through a variety of cytokines and growth factors in an orchestrated response that results in progressive parenchymal damage and loss of function within the irradiated volume.² Damage to the vasculature and release of vasoactive cytokines lead to increased vascular permeability, deposition of fibrin in the perivascular interstitium, and subsequent replacement by collagen.^4,8 An increase in collagen content can be seen as early as 1 week following irradiation.⁸

Following radiation therapy to the oral cavity, pharynx, or larynx, the mucous membranes can become erythematous within 1 week, and develop areas with white pseudomembranes (mucositis) at about 2 weeks.⁷ The patches of mucositis may coalesce by the third week.⁷ This acute mucosal reaction usually heals within 2 to 4 weeks following completion of radiotherapy, although ulceration and necrosis can occur.⁶ Late effects of radiation on the mucosa are characterized by thinning or atrophy of the epithelium, telangiectasia, dryness, a loss of mucosal mobility, submucosal induration, and occasionally chronic ulceration and necrosis.⁸ The mucosa is fragile and more susceptible than normal to mechanical injury.⁷ Edema is seen in the subcutaneous or submucosal soft tissue in the early phase following radiotherapy, can persist for 6 to 12 months,⁹ and can become chronic.^5,10

Edema occurs when vascular permeability is increased by inflammatory mediators or when venous or lymphatic passages are obstructed¹¹ and is associated with duration of radiotherapy treatments, dose per fraction, total number of fractions, number of fractions per day, and interval between fractions.¹² Radiotherapy-induced laryngeal edema occurs on a continuum from mild to severe,¹² and can be graded from 0 (absent) to 4 (necrosis).¹³ After radiotherapy for head and neck cancer, 15% to 59% of patients develop ≥Grade 2 laryngeal edema within 2 years.¹⁴ Grade 2 (moderate) edema is not associated with significant or symptomatic airway obstruction.¹³ However, severe laryngeal edema (Grade 3) may cause airway obstruction and require urgent tracheotomy.¹⁴ Laryngeal edema which persists for more than 3 months after radiotherapy may suggest the presence of residual or recurrent tumor.¹⁴ Local recurrence in about 50% of patients was noted to be associated with persistent laryngeal edema.¹⁴

The pathogenesis of radiation fibrosis is complex. Radiation of fibroblasts leads to induced differentiation and a significant increase in collagen deposition¹⁵ and radiation fibrosis may be considered to be a form of injury response in which there is a continuous signal for connective tissue deposition and/or a failure of regulatory processes that normally terminate fibrogenesis.¹⁶ Fibrosis is one of the most common delayed radiation-associated manifestations.⁷ It usually appears in subcutaneous tissues within 6 to 12 months of treatment,⁷ although it can occur as early as 4 to 12 weeks.⁸ The fibrosis tends to be slowly progressive,⁷ nonhomogeneous, and variable in extent and severity from site to site.¹⁷ The severity of the fibrosis increases when high total doses of radiation and large fraction sizes are used.⁶ The risk of developing moderate to severe fibrosis has been reported to be about 40%.⁵ The affected soft tissue loses elasticity and subcutaneous fat⁸ and is indurated to palpation.^1,8 In the presence of moderate to severe fibrosis, contracture of the tissues also occurs.¹ In severe cases, the soft tissues develop a woody consistency and may form a hard mass fixed to skin and underlying muscle or bone (see Figure 36–1).⁷ Obstructive lymphedema may also be associated with fibrosis.⁷ Radiation therapy to the neck can produce a limitation of neck extension (see Figure 36–2).^8,18 High-dose irradiation of metastatic cervical lymphadenopathy results in more subcutaneous fibrosis in the neck than does a comparable dose in the absence of palpable lymphadenopathy.⁷

Voluntary muscle exposed to high-dose irradiation can also develop fibrosis, and when the muscles of mastication (the temporalis, masseter, and pterygoid muscles) are involved, trismus can be produced (see Figure 36–3).⁷ The temporomandibular joint itself is however relatively resistant to ankylosis secondary to radiation injury.⁷ Radiotherapy has been reported to reduce mouth opening by 18% (SD, 17%) within 12 months of follow-up.^19,20 Although trismus may be apparent during the course of radiation therapy, it may not become apparent until 3 to 6 months after radiotherapy,¹⁹ The prevalence of trismus after radiotherapy for head and neck cancer has been reported to be between 5% and 38%.^20,21 Fibrosis of the pharyngeal musculature can produce swallowing dysfunction²² and a predisposition to aspiration.³ Hypopharyngeal stenosis is caused by fibrosis of the lamina propria and submucosa.²³ Stenosis of the pharynx or supraglottic larynx can occur and lead to airway compromise (see Figures 36–4 to 36–10).^7,23–26 Choanal stenosis thought to be associated with severe mucosal reaction followed by fibrosis has also been reported after radiotherapy for nasopharyngeal carcinoma.²⁷ Radiotherapy in head and neck cancer patients has also been associated with the development of obstructive sleep apnea.²⁸ The cause is likely multifactorial and may include persistent mucosal edema, decreased elasticity, increased fibrosis, and poor pharyngeal constriction.²⁸

Radiation therapy can also produce vascular injury which includes intimal thickening, fragmentation of the internal elastic membrane, atheroma formation, and fibrosis of the media and adventitia.⁷ In medium-sized vessels intimal fibrosis is the most common lesion.¹⁶ The capillary network is particularly vulnerable to radiotherapy and obstruction can occur due to endothelial cell injury and thrombosis.¹⁶ Telangiectasia and atrophy are common late effects^15,16 and a reduction in the microvascular network can ultimately lead to ischemia.¹⁷ Tissue ischemia may be a consequence of or contribute to the radiation injury.¹⁶ Narrowing or obstruction of larger arteries can also occur, as can occlusive thrombosis.¹⁷ The changes in the vessel walls are similar to those associated with artherosclerosis due to aging.⁸ Symptomatic carotid atherosclerosis can be a result of cervical irradiation and may require surgical intervention.²⁹

Laryngeal cartilage covered by normal mucous membrane usually tolerates conventional fractionated high-dose radiation therapy.^6,7 However, arytenoid edema, chrondritis, vocal cord palsy,^3,30 and rarely, chondronecrosis can occur (see Figures 36–4B, 36–5B, 36–7, 36–8B, 36–9B, and 36–10).¹ Laryngeal edema can occur at any time following the completion of radiation therapy²⁹ and can produce airway compromise.¹⁰ Stenosis of the larynx especially at the glottic level associated with fixation of the vocal cords due to scar at the posterior glottis is not unusual after radiotherapy for carcinoma of the larynx.²⁵ Laryngeal chondronecrosis has been reported to occur up to 22 years following radiotherapy.¹⁰

Radiation injury to the salivary glands produces a decrease in saliva production and a change in the composition of saliva.⁷ Typically, about 60% to 65% of the total salivary volume is produced by the parotid glands, 20% to 30% by the submandibular glands, and 2% to 5% by the sublingual glands.⁷ The remainder of the salivary volume is produced by anonymous minor salivary glands distributed throughout the oral cavity and pharynx and which are variable from patient to patient.⁷ The degree of salivary gland dysfunction depends on the volume of the glands included in the radiation field and the total dose administered.⁷ It is usually not possible to irradiate the pharynx or the upper jugular nodes without irradiating the submandibular glands; however, the parotid and submandibular glands can be partially shielded during treatment.⁶ Intensity-modulated radiotherapy can also be used to preserve salivary flow.^31,32 A significant reduction in salivary flow occurs within 1 week of fractionated radiotherapy to the head and neck.⁷ Salivary flow may become barely measurable by the end of a 6- to 8-week course of treatment and the xerostomia may be permanent.⁸ Xerostomia causes discomfort, alters taste acuity, and contributes to a deterioration in dental hygiene because the tissues become tender.⁷ The diminished salivary flow has an altered electrolyte content and reduced pH, and promotes dental decay as the normal oral microflora is altered to a highly cariogenic microbial population.⁷ In the absence of stringent measures to protect the teeth, caries can develop within 3 to 6 months and lead to complete destruction of the dentition within 3 to 5 years.⁷ Dental extractions from an irradiated mandible can precipitate osteoradionecrosis.⁶ Infection of the underlying bone related to carious teeth can also lead to osteoradionecrosis more commonly seen in the mandible due to its relatively poor blood supply as compared to the maxilla.⁴

Hypothyroidism occurs in 5% to 10% of patients who undergo irradiation of the lower neck,⁶ and fibrosis of the apical segments of the lungs can also occur.⁷

Patients with collagen vascular diseases such as scleroderma, rheumatoid arthritis, and systemic lupus erythematosis appear to have an increased incidence and severity of late normal tissue radiation toxicity¹⁶ and comorbidities with impaired vascularity such as diabetes and hypertension may have an adverse effect.⁴ Age may also be a factor.⁴

The patient presented here had palpable fibrosis of the submandibular tissues, decreased cervical extension, trismus, complete loss of mandibular dentition, and a dry mouth.

What Airway Management Difficulties Can be Anticipated Following Radiotherapy to the Oral Cavity, Pharynx, Larynx, or Neck?

Radiotherapy to the oral cavity, pharynx, larynx, or neck can result in limited mouth opening, limited cervical spine extension, noncompliant immobile fibrotic soft tissue in the floor of the mouth and pharynx, edema and fibrosis of the laryngeal walls,³¹ and vocal cord dysfunction.³⁰ Airway management can be difficult in the presence of these anatomic changes. The degree of difficulty is dependent on the site and extent of the altered anatomy.

Can Ventilation by Face Mask or Extraglottic Device be Anticipated to be More Difficult After Radiotherapy to the Structures of the Upper Airway?

In a review of 53,041 general anesthetics in which mask-ventilation had been attempted, Kheterpal et al.³³ identified 77 cases of impossible mask-ventilation (0.15%). Of the 77 patients who were impossible to mask-ventilate, 19 (25%) also demonstrated difficult intubation. However, the incidence of difficult intubation in the subgroup of patients with neck radiation was not provided.³³ Both univariate and multivariate analyses demonstrated neck radiation to be the most significant clinical predictor of impossible mask-ventilation. Of the subgroup of 310 patients with neck radiation, three could not be ventilated. Severely limited mandibular protrusion is an independent predictor of difficult (inadequate, unstable, or requiring two providers) mask-ventilation,³⁴ and neck radiation can be associated with reduced mandibular mobility. Limited or severely limited mandibular protrusion is an independent predictor of difficult or impossible mask-ventilation combined with difficult intubation.³⁴ In 2013 Kheterpal et al.³⁵ reported an incidence of 0.4% for difficult mask-ventilation (DMV) combined with difficult laryngoscopy (DL) in a series of 176,679 patients undergoing general anesthesia. DMV was defined as Grade 3 (inadequate to maintain oxygenation, unstable, or requiring two providers) or Grade 4 (impossible), and DL as Cormack–Lehane 3 or 4 views or ≥4 intubation attempts inclusive of direct or video-laryngoscopy. Neck mass or radiation was an independent predictor of DMV combined with DL.³⁵ Mask-ventilation and laryngoscopy serve as primary rescue techniques for each other and the inability to mask-ventilate in the setting of a difficult intubation has significant potential for morbidity and mortality.^34,35

Giraud et al.¹⁸ reported face-mask-ventilation to be easy following induction of general anesthesia in nine patients after oral or cervical radiation. Laryngeal mask airway (LMA) placement was often difficult but was successful in all five patients who had received oral radiotherapy, and ventilation was satisfactory.¹⁸ Two patients required lateral introduction of the LMA due to limitation of mouth opening.¹⁸ LMA placement was easy in the four patients who had received cervical radiation, but positive-pressure ventilation was difficult.¹⁸ On fiberoptic examination through the LMA, the vocal cords could not be visualized in any of these four patients due to vestibular-fold collapse. A large epiglottis was also seen in two of these patients. Muscle relaxation did not improve the laryngeal view. Ventilation was impossible in two of the four patients; however orotracheal intubation was successful. Bronchoscopic intubation via the LMA was not attempted as the glottis could not be visualized. The authors theorized that the presence of the LMA in a narrowed, non-distensible hypopharynx may have compressed the larynx and thereby produced glottic collapse.¹⁸

Ferson et al.³⁶ reported the use of the Intubating LMA-Fastrach (ILMA) in 254 patients with difficult-to-manage airways, of whom 40 had airway changes related to previous surgery, radiation therapy, or both. In this subset of patients, the authors reported that correct positioning of the ILMA was more difficult, and 10 patients required the use of a smaller ILMA than that indicated by the patient’s height and weight. There were no failures to insert the ILMA and ventilation was possible in all cases. Bronchoscopically guided intubation through the ILMA was also successful in all 40 patients. The authors felt that a loss of elasticity due to fibrosis in the neck tissues caused positioning of the ILMA to be more difficult and suggested that bronchoscopic guidance be used when attempting intubation through the ILMA in this group of patients.³⁶