Oh Snap! Ketamine-Induced Laryngospasm in an Adult Patient

A 58-year-old male with a history of prediabetes and hypertension presented to the emergency department by ambulance for left elbow pain after falling off a 10-foot ladder.

He slipped and fell backward off the ladder while working, landing on his left side. He denied any loss of consciousness. In addition to severe left elbow pain, he reported pain in his lower back and right shoulder. A review of systems was otherwise negative.

On arrival, the patient had a heart rate of 97, respirations of 16, blood pressure of 150/87, oral temperature of 36.7, and saturation of 97% on room air. His physical exam was significant for moderate distress secondary to pain, an obvious deformity to his left elbow with exquisite tenderness to palpation, limited range of motion at the affected joint, intact distal neurovascular function, mild tenderness to palpation at the right shoulder and humerus, and moderate tenderness to palpation of the left lumbar paraspinal region. X-rays of his left elbow demonstrated a posterior dislocation. Additional X-rays of his right shoulder, humerus, and forearm were unremarkable. CT scans of his head and entire spine were unremarkable. Bloodwork also was unremarkable.

A total of 1 mg/kg of ketamine was given for procedural sedation for reduction of his elbow. The rate of infusion was not recorded. Initial reduction was successful; however, the laxity of the joint led to near-immediate repeat dislocation. While attempting to hold the reduction, the patient began having high-pitched sonorous respirations concerning for laryngospasm. The physician at head-of-bed immediately applied pressure to Larson’s notch; however, the patient began to desaturate. Bag-valve-mask ventilations were initiated. Saturations normalized briefly before dropping again, despite bagging and manual airway-opening maneuvers. The decision was made to perform rapid sequence intubation. A paralytic was unable to be obtained in a timely manner, and attempts to ventilate with application of pressure at Larson’s notch and head tilt/jaw-thrust techniques were unsuccessful; thus the patient’s neck was prepped for cricothyrotomy. Before an incision could be made, the patient’s respirations improved, and he was successfully bagged up to a normal saturation.

Overview
Laryngospasm is a rare complication of ketamine, found in one systematic review to be 4.2 per 1000.¹ Cases necessitating advanced airway management are even rarer. In that same review, out of 883 ketamine sedations, the lone case of laryngospasm was resolved with conservative measures. The vast majority of incidents are brief and responsive to manual airway maneuvers and bagging.

Physiology
The physiology of laryngospasm is thought to be an exaggerated glottic closure reflex in which the superior laryngeal nerve activates adductor and constrictor muscles of the vocal cords, creating sphincteric closing of the glottis. This reflex allows us to swallow without aspiration. Expiratory phase, decreased PaCO2, increased PaO2, and negative intrathoracic pressure facilitate glottic closure.²

Epidemiology
Laryngospasm occurs more frequently and with greater severity in pediatric patients. In one meta-analysis, adults have an incidence of 4.2 per 1000. Children up to the age of 9 years have an incidence of 17 in 1000 cases. Children between 3 and 6 months have an incidence three times greater, thought to be secondary to increased parasympathetic tone and narrower airways.³ Obese patients, particularly with a history of sleep apnea, also are at an increased risk.³

Less relevant to emergency medicine is the association with airway instrumentation. It’s thought that laryngospasm in ketamine administration is due to salivation leading to ventilatory obstruction. Additional associations have been found with Down syndrome, Parkinson’s disease, hypocalcemia, hypomagnesemia, nasogastric tubes, and secondhand smoke exposure.^4,5

There is no clear association with dose. There is insufficient evidence regarding any association with the rate of ketamine administration; however, it is recommended to administer over 1-2 minutes to reduce the risk of respiratory depression.

Identification
Laryngospasm is not always easily identifiable. In its textbook form, it presents as a high-pitched inspiratory stridor — or “crowing” noise — which may proceed to silent, complete airway obstruction. Other less obvious signs include vomiting, increased work of breathing, or desaturation.⁶ Complete airway obstruction is defined by an absence of chest wall movement and lung sounds, abrupt loss of end-tidal waveform, and inability to ventilate.

Management and Literature Review
Untreated laryngospasm is complicated by hypoxia which, if not addressed, can progress to cardiac arrest. Another complication is acute vacuum-associated pulmonary edema caused by negative intrapleural hydrostatic pressure.

The recommended approach to ketamine-induced laryngospasm is to begin with application of pressure at Larson’s notch.⁷ Supplemental oxygen should be provided as needed. Sedation may be deepened, particularly with the use of propofol.⁵ If the patient is not responsive to these basic maneuvers, then bag-valve-mask ventilations must be initiated.

If the above measures fail and the patient cannot be ventilated, administration of propofol (1 to 2 mg/kg) resolves 80% of cases.⁵ If propofol is not readily available or ineffective, paralytics are indicated. Intravenous succinylcholine at a dose of 0.1 mg/kg is effective at stopping laryngospasm. Its rapid onset and shorter duration of action make it preferable to rocuronium in this situation, unless otherwise contraindicated. A larger dose (0.3 to 0.5 mg/kg) may be given for anticipated RSI, though bagging the patient without an advanced airway until the paralytic wears off is also an option. IV nitroglycerin (4 mcg/kg) also has been found to reverse laryngospasm.⁸

One study showed decreased incidence of laryngospasm in pediatric patients who were pre-treated with 0.5 mg/kg IV propofol, with an incidence of 20% in placebo vs. 6.6% in the treatment arm.⁹ It is reasonable to consider ketofol (combination of ketamine and propofol) for this reason. In fact, there is evidence that ketofol has a lower rate of adverse events than ketamine or propofol alone.¹

Magnesium has been trialed, with some success, as a pre-treatment to relax laryngeal muscle in patients undergoing upper airway surgery.¹⁰ Studies have been performed to assess the role of anticholinergics such as glycopyrrolate in reducing the risk of laryngospasm, so far demonstrating no difference in outcomes.¹¹ Lidocaine (1 to 2 mg/kg IV or aerosolized) is effective in both preventing and treating laryngospasm, reducing its incidence by 19% to 30%.^12,13,14Coadministration of ketamine with benzodiazepines has demonstrated reduced incidence of laryngospasm with a number needed to treat of 26.⁶

Overall, laryngospasm is rare. When it does occur, it almost always resolves with simple interventions such as application of pressure to Larson’s notch and assisted positive pressure ventilation. Paralytics may be necessary in rare circumstances. There are potential prophylactic measures for those at increased risk such as children, obese patients, and patients undergoing instrumentation of their upper airway. These measures include coadministration of propofol or benzodiazepines with ketamine and pretreatment with lidocaine or magnesium.

Case Conclusion
Approximately 45 minutes after the laryngospasm resolved, the patient was awake without respiratory distress or oxygen requirement. He was oriented except for amnesia regarding the event. Orthopedics was consulted due to repeated failed attempts at maintaining reduction of the elbow in the emergency department. A CT of his left upper extremity showed bone fragments within the joint. The patient was placed in a posterior slab splint, admitted to trauma, and taken to the operating room by orthopedics the following day for definitive management of his posterior elbow dislocation and fracture. He was discharged from the hospital without any neurological deficits.

References

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2. Ikari T, Sasaki CT. Glottic Closure Reflex: Control Mechanisms. Annals of Otology, Rhinology & Laryngology. 1980;89(3):220-224.
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