Status asthmaticus is a common cause of morbidity and mortality and the addition of ketamine to standard treatment for severe asthma has been associated with improved outcomes and a reduced need for mechanical ventilation. Notably, a 2013 review article evaluated the pulmonary effects of ketamine and whether sufficient evidence supports its use in refractory status asthmaticus. The review identified twenty reports involving a total of 244 patients ranging in age from 5 months to 70 years. Ketamine was used in different settings: in 13 articles (53 patients), it served as a rescue agent for patients with respiratory failure requiring mechanical ventilation; in 3 reports (58 patients), it was used as an anesthetic during surgery in asthmatic patients; in 3 studies (131 patients), it was administered in the emergency department to patients with status asthmaticus; and in 1 study (2 patients), it was used postoperatively for analgesia and sedation. Ketamine was initiated only after a poor response to first-line therapies. It was given as a bolus dose ranging from 0.1 mg/kg to 2 mg/kg, followed by continuous infusion at rates of 0.15 mg/kg/h to 2.5 mg/kg/h, depending on initial response; infusions lasted from 1 hour to 5 days. [1]
The findings suggested that patients experienced clinical improvement, reduced wheezing, and improved oxygen saturation and blood gas values. Mechanically ventilated patients showed reduced peak inspiratory pressures, improved dynamic lung compliance, enhanced gas exchange, and decreased oxygen requirements. These changes often allowed successful weaning from mechanical ventilation. In two studies, however, the response to ketamine was insufficient. No major adverse effects were reported in any of the studies; minor side effects included dysphoria, hallucinations, increased secretions, and mild changes in heart rate and blood pressure. Experimental studies also suggested that ketamine can alter respiratory mechanics and promote airway relaxation through various mechanisms, including interaction with receptors and inflammatory pathways involved in bronchospasm. In the included reports, patients with severe bronchospasm on mechanical ventilation experienced improvements in peak inspiratory pressure, gas exchange, dynamic compliance, and minute ventilation, allowing for successful weaning after ketamine initiation. Overall, across the reviewed studies, ketamine appeared to act as a potential bronchodilator in severe asthma. However, further robust research is needed before definitive recommendations can be made regarding its use in status asthmaticus. [1]
A 2012 Cochrane review evaluated the efficacy of ketamine compared to placebo, no intervention, or standard care in children with severe acute asthma who had not responded to standard therapy. Only one randomized controlled trial (RCT), which enrolled 68 non-intubated children, met the inclusion criteria. In this study, ketamine was administered as a 0.2 mg/kg intravenous bolus over one to two minutes, followed by a 0.5 mg/kg per hour continuous infusion for two hours. The study was assessed to have low or unclear risk of bias and demonstrated no significant difference in respiratory rate, oxygen saturation, hospital admission rate, or need for mechanical ventilation between the ketamine and placebo groups. Specifically, the odds ratio (OR) for hospital admission was 0.77 (95% confidence interval [CI] 0.23 to 2.58). There was also no significant difference in the need for other adjuvant therapy (OR 2.19; 95% CI 0.19 to 25.40), or in Pulmonary Index Score (mean difference 0.40; 95% CI 1.21 to 0.41). No significant side effects of ketamine were reported. Overall, this single study did not show a significant benefit of ketamine and does not support previous case studies and observational reports suggesting benefit in both non-ventilated and ventilated children. Although ketamine may relieve bronchospasm and remains a potentially promising therapy for children with acute asthma who do not respond to standard treatment, sufficiently powered randomized trials with objective outcome measures of clinical importance are needed to determine its effectiveness. [2], [3]
A 2021 randomized clinical trial evaluated the effects of nebulized ketamine versus intravenous magnesium sulfate in patients with corticosteroid-resistant acute asthma exacerbations. Seventy patients were randomized 1:1 to the ketamine group (n= 35) and the magnesium sulfate group (n= 35). All patients received standard therapy prior to the intervention. Patients in the ketamine group received nebulized ketamine at a dose of 0.1-0.3 mL/kg, while patients in the magnesium sulfate group received 2 g of intravenous magnesium sulfate infused over 20 minutes. In the ketamine group, the mean peak expiratory flow rate (PEFR) before intervention was 360.71 ± 83.31. PEFR increased to 376.0 ± 81.28 at 30 minutes and 390.12 ± 79.44 at 60 minutes post-intervention, representing a 29.42% increase from baseline. These changes were statistically significant (p<0.001). The hospitalization rate in the ketamine group was 46% (13 of 35 patients). In the magnesium sulfate group, the mean baseline PEFR was 332.85 ± 74.72. PEFR increased to 345.57 ± 71.80 at 30 minutes and 356.28 ± 71.98 at 60 minutes, corresponding to a 15.28% increase from baseline, which was also statistically significant (p<0.001). The hospitalization rate in this group was 54% (15 of 35 patients). While both groups demonstrated significant improvements in PEFR and reductions in hospital admission rates, the differences between the two groups were not statistically significant for either hospitalization rate (p= 0.5) or PEFR improvement (p= 0.1). Due to these findings, it was concluded that both nebulized ketamine and intravenous magnesium sulfate, when added to standard therapy, are effective in improving PEFR and relieving bronchospasm in patients with severe steroid-resistant asthma. Although nebulized ketamine resulted in a greater numerical improvement in PEFR and lower hospitalization rate compared to magnesium sulfate, these differences were not statistically significant. [4]