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Correspondence  |   June 2007
Treatment of Supraglottic Airway Edema by Local Hyaluronidase
Author Affiliations & Notes
  • Keshavan H. Venkatesh, M.D., D.N.B.
    *
  • *National Institute of Mental Health Neurosciences, Bangalore, India.
Article Information
Correspondence
Correspondence   |   June 2007
Treatment of Supraglottic Airway Edema by Local Hyaluronidase
Anesthesiology 6 2007, Vol.106, 1254-1255. doi:10.1097/01.anes.0000265425.52996.fc
Anesthesiology 6 2007, Vol.106, 1254-1255. doi:10.1097/01.anes.0000265425.52996.fc
To the Editor:—
The incidence of laryngeal edema after extubation is approximately 2–15%.1 Supraglottic edema, which is one of the causes of failed extubation, is most often underdiagnosed because of its spontaneous regression.2 However, in its severe form, it may necessitate reintubation and long-term airway care, associated with high morbidity. Hyaluronidase has been used in various clinical conditions to reduce tissue edema,3,4 but its use to reduce supraglottic airway edema has not previously been reported. Over the past 5 yr, we used hyaluronidase to relieve airway obstruction caused by supraglottic edema that interfered with extubation of the tracheostomy in seven patients with neurologic disease. These patients were receiving ventilatory support via  oral or nasal endotracheal tube and tracheostomy tube for 19 days (range, 10–28 days) and 21 days (range, 10–56 days), respectively. Five patients underwent a tracheostomy as an elective procedure for their poor neurologic condition, and two patients required tracheostomy because of stridor after extubation, which did not respond to medical treatment. When the patients were considered ready for decannulation, the tracheostomy tube was reduced to a smaller size for a few days followed by attempted occlusion. Attempt at tracheostomy tube occlusion was considered as failed when the patient developed stridor or paradoxical breathing immediately or within a few hours of occlusion.
All of the patients received intravenous injection of 4 mg dexamethasone 8 hourly and oral trypsin–chymotrypsin (Chymoral forte®, a combination of 100,000 Armour units of enzymatic activity of trypsin and chymotrypsin in the ratio of 6:1; Elder Pharma, Maharashtra, India) 8 hourly for 3 days before the trial of tracheostomy occlusion. All patients underwent a diagnostic bronchoscopy when extubation failed. The major finding in all of the patients was supraglottic airway edema, which narrowed the laryngeal inlet (fig. 1A). The arytenoids, supraglottic area, and vocal cords were edematous. Five patients had no pathology in the subglottic region, at the tracheostomy stoma or up to the tracheal bifurcation. Subglottic suprastomal edema was seen in one patient. One patient had severe subglottic stenosis. On occlusion of the tracheostomy tube during bronchoscopy, the edematous tissue in the supraglottic area caved in, narrowing the laryngeal inlet further.
Fig. 1. Bronchoscopic view in a patient showing severe laryngeal inlet edema obstructing the airway before injection of hyaluronidase (  A  ) and resolution of edema 48 h after hyaluronidase injection (  B  ). 
Fig. 1. Bronchoscopic view in a patient showing severe laryngeal inlet edema obstructing the airway before injection of hyaluronidase (  A  ) and resolution of edema 48 h after hyaluronidase injection (  B  ). 
Fig. 1. Bronchoscopic view in a patient showing severe laryngeal inlet edema obstructing the airway before injection of hyaluronidase (  A  ) and resolution of edema 48 h after hyaluronidase injection (  B  ). 
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After the diagnosis of supraglottic edema, a direct laryngoscopy was performed. Freshly prepared hyaluronidase solution of 750 U in 1 ml was injected into the submucosal tissue of the edematous supraglottic area, using a 10-cm-long, 23-gauge spinal needle. All patients received one injection of 750 U hyaluronidase. The dose of hyaluronidase varies in different clinical situations. A total dose of up to 300 U has been used to relieve edema in paraphimosis. In our patients, considering the severity of the edema, a total dose of 750 U was used. In a recent case report, a dose of 1,500 U was used in the treatment of extensive edema to facilitate reduction of intusussception.4 In one patient who had subglottic suprastomal edema, hyaluronidase was injected into the subglottic tissue using a transtracheal approach under direct vision through the bronchoscope. Fiberoptic bronchoscopy was repeated 24–48 h after hyaluronidase injection. Occlusion of the tracheostomy tube was attempted when there was bronchoscopic evidence of resolution of the edema. Repeat bronchoscopy 24–48 h after the injection of hyaluronidase showed a significant reduction of the supraglottic airway edema (fig. 1B). On occlusion of the tracheostomy tube, all patients except one could breathe comfortably around the tube. One patient with severe subglottic narrowing could not tolerate the occlusion and required the tracheostomy tube to be left in situ  . Occlusion of the tracheostomy tube could be started within 48 h of hyaluronidase injection in six patients, and decannulation was successful over the next 24–48 h in five patients. One patient died before decannulation due to causes unrelated to airway compromise. Tracheostomy occlusion failed in one patient with severe subglottic stenosis; this patient required a surgical correction later.
Prolonged tracheal intubation and tracheostomy predispose to laryngotracheal stenosis.5 The major abnormalities commonly reported after prolonged tracheal intubation or tracheostomy are glottic stenosis, granulomas, subglottic stenosis, and tracheomalacia.6,7 Supraglottic edema as the primary cause of failed tracheostomy tube decannulation is rarely reported. In our patients, we proved by bronchoscopy that supraglottic airway edema was solely responsible for failed decannulation in five of the seven patients.
In a series of pediatric patients, Cotton and Myer8 showed that the first bronchoscopy, performed to examine the cause for failed extubation, showed supraglottic airway narrowing. The cause for supraglottic narrowing could be multifactorial: intubation trauma, tube–tissue interface in the posterior larynx, coughing on the tube due to inadequate sedation or persistent hypotension. These factors result in trauma to the tracheal mucosa at the tube–tissue interface resulting in airway edema.9 
Conservative treatment of supraglottic edema in the acute phase generally consists of corticosteroids and epinephrine nebulization. Many studies, however, did not demonstrate the efficacy of corticosteroids in this setting.10–12 In our series also, the patients developed stridor despite dexamethasone therapy for 72 h before attempted tracheostomy closure. When our patients did not respond to conservative management including corticosteroids, we used hyaluronidase for its ability to increase the membrane permeability and promote resorption of the edema fluid.
Allergic reactions and angioedema after hyaluronidase injection have been reported. Most of these reports are related to its use in ophthalmic surgery.13,14 None of our patients had any such complications of hyaluronidase. Hyaluronidase is not indicated in the presence of local infection because this may facilitate spread of infection. The usefulness of hyaluronidase in reducing the airway edema has not been previously reported. Hyaluronidase may not be useful in patients who have permanent structural damage with fibrosis as the underlying pathology, as it happened in one of our patients.
In conclusion, our case series indicates that failure of extubation or tracheostomy decannulation could result from supraglottic edema. Local hyaluronidase injection may be considered an option to treat this form of airway edema when other medical measures have failed.
*National Institute of Mental Health Neurosciences, Bangalore, India.
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Fig. 1. Bronchoscopic view in a patient showing severe laryngeal inlet edema obstructing the airway before injection of hyaluronidase (  A  ) and resolution of edema 48 h after hyaluronidase injection (  B  ). 
Fig. 1. Bronchoscopic view in a patient showing severe laryngeal inlet edema obstructing the airway before injection of hyaluronidase (  A  ) and resolution of edema 48 h after hyaluronidase injection (  B  ). 
Fig. 1. Bronchoscopic view in a patient showing severe laryngeal inlet edema obstructing the airway before injection of hyaluronidase (  A  ) and resolution of edema 48 h after hyaluronidase injection (  B  ). 
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