Ketamine for Adults with Severe Asthma Exacerbation: A Systematic Review and Meta-analysis

BACKGROUND: Severe asthma mandates careful attention and timely management, and the benefit of ketamine in severe asthma exacerbations in adult patients require further exploration. METHODS: We conducted a systematic review and meta-analysis of the use of ketamine in cases of acute asthma exacerbation in adults. We searched PubMed, Google Scholar, Cochrane databases, and gray literature (ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform); we also searched the reference lists of included articles and any systematic reviews and meta-analyses identified therein. Our search covered the period from 1963 to August 20, 2021. Search terms were “ketamine” AND “asthma”. RESULTS: Of 25 540 articles, two studies were included in the analysis. The total number of patients included in the studies was 136 (68 in the ketamine groups and 68 in the placebo group). The pooled effect size was 0.30 (95% CI: -0.04, 0.63) favouring ketamine over placebo, p=0.08, (I2=0%, p=0.39). A paired t-test revealed that ketamine improved the mean peak expiratory flow rate (PEFR) from 242.4 (SD=146.23) to 286.95 (SD=182.22), p=0.33, representing an 18.38% improvement. CONCLUSION: Ketamine can induce a 30% improvement in PEFR, representing a small positive effect in the treatment of acute severe asthma exacerbation in the emergency department (ED). The improvement was not statistically significant; nonetheless, since the improvement could be as great as 63% versus only a 4% possibility of no benefit/harm, the benefit appears to considerably outweigh any harm.

New onset asthma during pregnancy: two case reports

Introduction: Asthma is the most common chronic respiratory disease during pregnancy. However, reports of new onset asthma during pregnancy are lacking. We report two cases of new onset asthma during pregnancy following respiratory tract infection, subsequently one case with M. pneumoniae infection and the other case with a combined infection with respiratory syncytial virus and rhinovirus. Case presentation: Both patients presented with the clinical features of an acute asthma exacerbation during pregnancy without a medical history of asthma. During follow up the diagnosis of asthma was supported by spirometry showing significant reversibility and elevated fractional exhaled nitric oxide (FeNO). Patients were hospitalized and received supplemental oxygen, treatment for an acute asthma exacerbation with systemic corticosteroids, high dose inhalation therapy. These therapeutic interventions subsequently led to a good outcome for the mother and newborn in both cases. Conclusions: New onset asthma should be part of the differential diagnosis in pregnant patients with respiratory symptoms, particularly in case of mycoplasma infection. Diagnosing asthma during pregnancy can be challenging. In these circumstances, additional diagnostic tests like inflammatory biomarkers FeNO and blood eosinophils) can be helpful to support the diagnosis.

Managing an acute asthma exacerbation in children

Children and youth with acute asthma exacerbations frequently present to an emergency department with signs of respiratory distress. The most severe episodes are potentially life-threatening. Effective treatment depends on the accurate and rapid assessment of disease severity at presentation. This statement addresses the assessment, management, and disposition of paediatric patients with a known diagnosis of asthma who present with an acute asthma exacerbation. Guidance includes the assessment of asthma severity, treatment considerations, proper discharge planning, follow-up, and prescription for inhaled corticosteroids to prevent exacerbation and decrease chronic morbidity.

Epinephrine (adrenaline) compared to selective beta-2-agonist in adults or children with acute asthma: a systematic review and meta-analysis

BackgroundInternational asthma guidelines recommend against epinephrine (adrenaline) administration in acute asthma unless associated with anaphylaxis or angio-oedema. However, administration of intramuscular epinephrine in addition to nebulised selective β2-agonist is recommended for acute severe or life-threatening asthma in many prehospital guidelines. We conducted a systematic review to determine the efficacy of epinephrine in comparison to selective β2-agonist in acute asthma.MethodsWe included peer-reviewed publications of randomised controlled trials (RCTs) that enrolled children or adults in any healthcare setting and compared epinephrine by any route to selective β2-agonist by any route for an acute asthma exacerbation. The primary outcome was treatment failure, including hospitalisation, need for intubation or death.ResultsThirty-eight of 1140 studies were included. Overall quality of evidence was low. Seventeen studies contributed data on 1299 participants to the meta-analysis. There was significant statistical heterogeneity, I2=56%. The pooled Peto’s OR for treatment failure with epinephrine versus selective β2-agonist was 0.99 (0.75 to 1.32), p=0.95. There was strong evidence that recruitment age group was associated with different estimates of the odds of treatment failure; with studies recruiting adults-only having lower odds of treatment failure with epinephrine. It was not possible to determine whether epinephrine in addition to selective β2-agonist improved outcomes.ConclusionThe low-quality evidence available suggests that epinephrine and selective β2-agonists have similar efficacy in acute asthma. There is a need for high-quality double-blind RCTs to determine whether addition of intramuscular epinephrine to inhaled or nebulised selective β2-agonist improves outcome.PROSPERO registration numberCRD42017079472.

Pre-vaccination allergy testing with COVID-19 mRNA vaccines predicts tolerance

Background: The newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis, possibly induced by polyethylene glycol (PEG) contained in the vaccine. The management of persons with a history of PEG allergy, or with an allergic-like reaction after the first dose remains to be defined. Methods: We studied two cohorts of individuals: one pre-vaccination, the second post-vaccination. Skin testing was performed with COVID-19 mRNA vaccines. Upon negative skin test, a two-step (10%-90%) vaccination protocol was performed. Positive skin tests were confirmed with basophil activation tests (BAT). Vaccine-sensitized patients were offered a five-step induction protocol. Results: We identified 187 patients with high-risk profiles for developing anaphylaxis. In parallel, among 385’926 doses of vaccine, 87 allergic-like reactions were reported to our division for further investigations: 18/87 (21%) were consistent with anaphylaxis, 78/87 (90%) were female, and 47/87 (54%) received the BNT162b2 mRNA vaccine. Vaccine skin tests were negative in 96% and 76% in the pre- and post-vaccination cohorts, respectively. A two-step vaccination was tolerated in 232/236 (98%) of individuals with negative tests. Four individuals experienced acute asthma exacerbation during the two-step challenge. Vaccine-positive skin tests were consistently confirmed by BAT; CD63 and CD203c expression was selectively inhibited with ibrutinib, suggesting an IgE-dependent mechanism. Finally, 13 sensitized patients were successfully vaccinated with a five-step vaccination protocol. Conclusion: A two-step 10%-90%-vaccination protocol can be safely administered upon negative skin testing. Yet, it should be delayed in individuals with poorly controlled asthma. Importantly, mRNA vaccine sensitized individuals may receive a five-step vaccination protocol.

Severe asthma that was endotracheally intubated 16 times in 20 years

Introduction: Severe asthma is a complex airway disease characterised by multiple aggravating-factors, and frequent comorbidities. Poor asthma control does not always correspond to the severity of airflow obstruction. One cause of disproportionate breathlessness in asthma is dysfunctional breathing/hyperventilation syndrome which is increasingly recognized. Case study: This female individual arrived at our asthma centre for the first time, coming from a primary care site 20 years ago. During the past 20 years she was intubated 16 times. Airway obstruction was never assessed surrounding the acute asthma episodes. Asthma diagnosis was confirmed by spirometry many times during routine visits at the asthma centre, where she never came to our asthma centre during an acute asthma exacerbation. Despite warranting the availability of controller medication with high ICS dose plus LABA, she repeated the episodes of severe dyspnoea requiring endotracheal intubations. Results: At a routine outpatient visit to our asthma centre for claiming her asthma medication, she developed an extreme dyspnoea as it occurred so many times earlier, using accessory respiratory muscles. The modified Borg scale for dyspnoea was 9/10. Pulse oximetry showed 96% O2 saturation breathing at room air. Baseline FEV1 was 1.96 L. Dyspnoea did not improve after 30 minutes of treatment. However, the FEV1 increased 29% to 2.53 L (96% predicted). Relaxation respiratory techniques began and the extreme dyspnoea slowly disappeared. Conclusion: Hyperventilation syndrome was confirmed with a score 32 with the Nijmegen Questionnaire (normal <23). Hyperventilation syndrome could coexist with severe asthma in 47% of cases. Keywords: Asthma; Asthma primary care; Hyperventilation syndrome.