The Journal of Emergency Medicine Gil Z. Shlamovitz, MD, Tracy Hawthorne, MHS, PA-C J Emerg Med. 2011;41(5):492-494.

Intravenous Ketamine in a Dissociating Dose as a Temporizing Measure to Avoid Mechanical Ventilation in Adult Patient With Severe Asthma Exacerbation
Abstract and Introduction
Abstract Background: Patients experiencing severe asthma exacerbations occasionally deteriorate to respiratory failure requiring endotracheal intubation and mechanical ventilation. Mechanical ventilation in this setting exposes the patients to substantial iatrogenic risk and should be avoided if at all possible. Objectives: To describe the use of intravenous ketamine in acute asthma exacerbation. Case Report: We present a case of severe asthma exacerbation in an adult female patient who failed to improve with standard therapies, but promptly improved with the administration of intravenous ketamine (0.75 mg/kg i.v. bolus followed by continuous drip of 0.15 mg/kg/h). Summary: This case suggests that intravenous ketamine given in a dissociative dose may be an effective temporizing measure to avoid mechanical ventilation in adult patients with severe asthma exacerbations. Introduction Patients experiencing severe asthma exacerbations occasionally deteriorate to respiratory failure requiring endotracheal intubation and mechanical ventilation. Mechanical ventilation in this setting exposes the patients to substantial iatrogenic risk and should be avoided if at all possible

Case Report
A 28-year-old Hispanic woman presented to our Emergency Department complaining of 8 h of progressively increased wheezing and shortness of breath. The symptoms started after exposure to dust and paint fumes at her home and did not respond to multiple albuterol treatments using a metered dose inhaler. The patient reported a history of childhood asthma with two prior admissions to the hospitalthe last admission (non-ICU [intensive care unit]) had been about 8 years prior. The patient's medications included montelukast 10 mg once daily, budesonide inhaled 90 g twice daily, and albuterol, inhaled as needed. The patient

denied any fevers, chills, cough, or chest pain. On physical examination, the patient was found to be awake and oriented, in severe respiratory distress, and could only speak one word at a time. Initial vital signs were: temperature 36.8C (98.4F), heart rate 124 beats/min, respiratory rate 35 breaths/min, blood pressure 187/119 mm Hg, and room air pulse oximetry 75%. Lung auscultation revealed markedly decreased breath sounds bilaterally with no audible wheezes. The patient was promptly started on nebulized (NEB) albuterol (7.5 mg) and ipratropium (500 g NEB) over 10 min followed by continuous albuterol inhalation (20 mg/h NEB) via face mask device (FIO2 40%) and epinephrine 0.3 mg intramuscularly. A fluid bolus of 1000 mL normal saline, dexamethasone 20 mg, and magnesium sulfate 2 g were administered intravenously. A chest radiograph showed hyperinflated lungs with no focal consolidation and no pneumothorax. Thirty minutes into the above-mentioned treatment, the patient seemed to be getting tired, with a decreased respiratory rate, no improvement in air exchange, and still no audible wheezing on chest auscultation. While setting up for rapid sequence intubation, stat arterial blood gases were obtained and showed pH 7.23; pCO2 62; pO2 86; HCO3 26; and O2 saturation (SAT) 94%. In an attempt to avoid intubation and mechanical ventilation, we administered ketamine 0.75 mg/kg i.v.p. 45 min after initiation of albuterol treatment with a 1-min onset of a dissociative state recognized by decreased responsiveness and nystagmus. The patient's respiratory rate decreased to 20 breaths/min and lung auscultation revealed bilateral improvement in air movement with audible wheezing. The patient woke up in 10 min, had an O2 SAT of 100%, and was able to speak three to four words at a time. About 30 min after administration of the ketamine bolus, the patient reported worsening shortness of breath. The O2 SAT decreased to 90%, and physical examination demonstrated bilateral decreased air movement and decreased wheezing. A second ketamine bolus of 0.75 mg/kg was administered intravenously, followed by continuous ketamine drip of 0.15 mg/kg/h with a 1-min onset of a dissociative state that lasted approximately 10 min. The patient's respiratory status showed marked improvement after the second bolus, as evidenced by increased bilateral air entry and loud audible wheezing. Upon awakening from the dissociative state, the patient reported significant improvement in her shortness of breath and was able to speak in five- to six-word sentences. The patient was kept on a ketamine drip and continuous nebulized albuterol for 2 more hours and was admitted to the ICU for close monitoring. The patient did not experience an exacerbation overnight, did not require intubation, and was transferred to a regular floor on the following day.

Discussion
Studies have shown an increase in prevalence and severity of asthma during the last 20 years despite publication and dissemination of evidence-based guidelines for the management of acute and chronic asthma. Patients experiencing severe asthma exacerbation occasionally deteriorate to respiratory failure and require mechanical ventilation. Mechanical ventilation in the setting of severe asthma exposes the patient to substantial iatrogenic risks, including pneumothorax, pneumomediastinum, nosocomial pneumonia, worsening bronchospasm, and circulatory depression, and therefore should be utilized only after other measures have failed.

Ketamine is a dissociative sedative frequently used by Emergency Physicians for procedural sedation and analgesia as well as an induction agent in status asthmaticus patients. Ketamine has demonstrated bronchodilatatory properties in both in vitro studies (relaxing bronchial smooth muscles) and mechanically ventilated status asthmaticus patients (decreasing mean airway pressure and PaCO2 and increasing PaO2). Suggested mechanisms of bronchodilatation include: sympathomimetic effect, direct relaxant effect, antagonism to histamine and acetylcholine, calcium influx blockage, and a membrane-stabilizing effect, as with local analgesics. It is also possible that the dissociating effect of ketamine may result in anxiolysis and a decrease in the work of breathing without depressing the respiratory drive. Our review of the literature (PubMed, accessed November 20, 2007) identified 14 case reports in which pediatric patients treated with ketamine successfully avoided mechanical ventilation. The administered dosages of ketamine in these case reports varied significantly and ranged from an intravenous bolus of 0.6 mg/kg to an intramuscular bolus of 4.8 mg/kg. The continuous intravenous ketamine infusions varied between 0 and 2.4 mg/kg/h. All children entered a dissociative state followed by marked clinical improvement, and none of them required mechanical ventilation. We identified two randomized, double-blind placebo-controlled trials evaluating the effectiveness of intravenous ketamine in asthma. Howton et al. studied 44 adults with severe asthma exacerbation and found no significant difference in outcome between the ketamine and placebo groups. Allen and Macias studied 68 children with moderate-to-severe asthma exacerbation and found no incremental benefit to standard therapy in the cohort group given ketamine. However, both studies used very low doses of ketamine (0.2 mg/kg bolus) and none of the patients entered a dissociative state. We believe that this low dosing is likely to explain the authors' findings.

Conclusions
In conclusion, our patient failed to respond to standard therapies, but promptly improved with the administration of intravenous ketamine. This case suggests that intravenous ketamine given in a dissociative dose may be an effective temporizing measure to avoid mechanical ventilation in adult patients with severe asthma exacerbations.