Abstract

Naloxone is commonly used to reverse narcotic intoxication. However, its use is not entirely free of hazards. For instance, pulmonary edema (PE) has been reported to arise with the mechanism of over-sympathetic discharge caused by release of cat-echolamine or central neurogenetic responses to narcotic reversal. Here, we report a healthy young patient who, after undergoing an uneventful uvulopalatopharyngo-plasty for obstructive sleep apnea hypopnea syndrome, developed PE following administration of naloxone. Fentanyl-induced respiratory depression was found during anesthesia emergence and thus naloxone was indicated for reversal. Unfortunately, upper airway obstruction-induced negative pressure PE occurred following naloxone administration. From this case, we suggest that a patent airway should be ascertained before naloxone administration for treating narcotic-induced respiratory depression.

Keywords

airway obstruction; naloxone; pulmonary edema;

1. Introduction

Naloxone is a drug that is used to reverse narcotic intoxication. However, its use may cause severe events such as cardiac arrest,¹ ventricular arrhythmia,^2,3 rupture of cerebral aneurysm,⁴ and pulmonary edema (PE).⁵⁻⁹ It has been suggested that naloxone-induced PE is caused by over-sympathetic discharge, in consequence of release of catecholamine, or central neurogenetic responses to narcotic reversal. Here, we report a case of negative pressure PE following naloxone administration for treating fentanyl-induced respiratory depression.

The possible mechanisms and clinical implications are discussed.

2. Case Report

A 21-year-old, 58-kg, 165-cm tall male patient was scheduled for uvulopalatopharyngoplasty because of obstructive sleep apnea hypopnea syndrome. His previous medical history was unremarkable. Preop erative studies revealed normal blood analysis, normal electrocardiogram and chest X-ray (Figure 1A).

No premedication was administered. Anesthesia was induced with intravenous thiopentone 300 mg, fentanyl 0.1 mg, and 2% lidocaine 80 mg. Tracheal intubation was facilitated by intravenous succinylcholine 80 mg. Anesthesia was maintained by isoflurane and 4 mg pancuronium. An additional 0.05 mg fentanyl was given during the operation. The procedure, which lasted for 2 hours, was completed uneventfully, and a total of 750 mL normal saline was infused. After reversal of residual neuromuscular blockade agent, the trachea was extubated under warrantable circumstances (eye opening, 0.1% endtidal isoflurane concentration, smooth respiration with a rate of 16 breaths/min, and sustained head lifting for more than 5 seconds). The patient was sent to the postanesthesia care unit (PACU) with stable vital signs.

Unfortunately, loss of consciousness and cyanosis emerged shortly after arriving in the PACU. The monitor showed bradycardia (heart rate, 45 beats/ min) and oxygen desaturation (SpO2, 55%). Face mask ventilation with 100% oxygen was immediately applied but ventilation was difficult. Placement of an oropharyngeal airway and chin lifting successfully helped to ventilate easier and SpO2 increased to 98%. However, the patient’s consciousness did not return, and spontaneous respiration was low (6 breaths/ min). Physical examination revealed pin-point pupils and clear breathing sounds bilaterally.

On suspicion that the respiratory episode was caused by the residual effect of fentanyl, intravenous naloxone 0.08 mg was administered. Immediately, the chest wall movement became vigorous, with an abnormal pattern of respiration (chest descending and abdomen ascending). Upper airway obstruction was suspected, so we repositioned the oropharyngeal airway and lifted the chin. Subsequently, vapor appeared on the mask and the patient started to cough and open his eyes. Five minutes later, the patient coughed badly and coughed up pinkish and frothy sputum. The patient was then placed in the sitting position and face tent with 100% oxygen was applied. The coughing and expectoration subsided 30 minutes later.

Chest X-ray revealed interstitial PE bilaterally with a normal-sized heart (Figure 1B). After SpO2 could be kept above 90% when breathing room air for 1 hour in the supine position, the patient was returned to the ordinary ward. Echocardiography revealed normal cardiac performance. Chest X-ray taken on postoperative day 2 showed that both lungs were clear.

Based on the clinical picture and rapid recovery, a diagnosis of upper airway obstruction-induced negative pressure PE was established. The patient was discharged on postoperative day 5 without any sequelae.

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Figure 1 (A) The patient’s preoperative chest X-ray shows bilateral clear lung fields. (B) The patient’s postoperative chest X-ray shows bilateral increased density with thickened interstitial line.

3. Discussion

Patients with obstructive sleep apnea hypopnea syndrome after uvulopalatopharyngoplasty may be subjected to postoperative respiratory complications (2−11%), which include airway obstruction (e.g. laryngospasm), postobstructive PE, and oxygen desaturation.¹⁰ Naloxone-induced PE is a rare complication. It can occur in patients with pre-existing heart disease,⁵ young healthy patients,⁶⁻⁹ with usual dosages of naloxone (0.2−0.4 mg),^1,3,5 or even with smaller dosages (0.04−0.08 mg).⁷ Thus, the administration of naloxone for narcotic reversal must be done with exceptional caution. The mechanism of PE secondary to naloxone has been discussed in many previous reports.¹⁻⁹ The presumed etiology is the occurrence of an adrenergic crisis with a large A B Figure 1 (A) The patient’s preoperative chest X-ray shows bilateral clear lung fields. (B) The patient’s postoperative chest X-ray shows bilateral increased density with thickened interstitial line. Pulmonary edema following naloxone infusion 157 increase in catecholamine release, which is harmful to patients with pre-existing heart disease.¹⁻⁵ It has been reported that plasma concentrations of norepinephrine and epinephrine can significantly increase following naloxone administration in fentanylpretreated dogs.¹¹ However, naloxone-induced PE could occur in young, healthy patients without significant hemodynamic change. In this situation, central neurogenetic response to narcotic reversal is hypothesized,⁶⁻⁹ which causes pulmonary vasoconstriction and pulmonary hypertension.

The differential diagnoses of PE in this patient include fluid overload, cardiac events, allergic reaction, aspiration, and idiosyncratic drug reaction to naloxone. The 750 mL of normal saline administered in 2 hours is not likely to have caused PE in this 58-kg young healthy patient. A cardiac cause was excluded by normal echocardiography and electrocardiography. Allergic reaction was also excluded in this patient because of the absence of skin rash, redness and tissue swelling. Clinical presentation and chest X-ray revealed no evidence of aspiration. However, PE secondary to naloxone could not be ruled out, even though only a small dose of naloxone (0.08 mg) had been administered and no subsequent significant hemodynamic responses had occurred. It has been reported that a small dose of naloxone can induce PE.⁷ However, the coexisting upper airway obstruction in this patient should be considered the major etiology of the resultant PE.

Clinically, upper airway obstruction may cause negative pressure PE.¹² In this instance, the patient suffered from fentanyl-induced respiratory depression combined with upper airway obstruction at the same time. Naloxone administration immediately improved respiration, but the upper airway obstruction remained unresolved. We agree with Gould¹³ that anesthesiologists who attended could have directly observed the development of PE even after one or two forceful inspiratory efforts against a stridorous or closed glottis by patients. Thus, in this case, we speculate that the recovering inspiratory efforts were so forceful that they induced negative airway pressure against the upper airway obstruction, and thus PE developed afterwards.

There are several issues worthy of discussion in this case. First, the patient did not show opioid intoxication signs until his arrival in the PACU. There was at least a 5-minute interlude between post-extubation stable condition and the onset of the incident. It is unclear why relapse of narcosis occurred in this patient. We speculate that residual fentanyl was released from the muscles due to postoperative shivering and movement. By experience, it is difficult to explain how 0.15 mg of fentanyl could cause respiratory depression. The observation of 0.1% end-tidal isoflurane concentration at the time of extubation in our patient and his head lifting that could be sustained for more than 5 seconds should rule out the residual effects of the volatile anesthetic and muscle relaxant, respectively. In actuality, the clinical findings of pin-point pupil, slow respiration rate and loss of consciousness, and the abolishment of these signs following naloxone administration, are sufficiently suggestive of fentanylinduced respiratory depression.

In summary, we have reported a patient who suffered from negative pressure PE following naloxone administration for treating fentanyl-induced respiratory depression. Upper airway obst ruction that occurred simultaneously was considered to be the cause of negative pressure PE. We suggest that a patent airway should be ascertained prior to naloxone administration for narcotic reversal.