Anaphylactic events in mRNA vaccines: a reporting case-control study

Background: mRNA vaccines are a novel method of eliciting immunity, and play a significant role in the global fight against COVID-19. Anaphylactic reactions are a widespread concern driving vaccine hesitancy due to the serious and potentially fatal nature of anaphylaxis. A quantitative estimation of the risk of anaphylactic and anaphylactoid reactions deriving from mRNA vaccines is of a significant public health importance. Objective: To estimate the relative Reporting Odds Ratio of anaphylactic and anaphylactoid reactions following mRNA vaccination vis-a-vis other vaccinations. Design: Reporting case-control study. Setting: Persons reporting adverse events following vaccination to VAERS whose reports were received between 01 January 2000 and 02 July 2021, inclusive. Patients: Each case of anaphylaxis or anaphylactoid reaction was matched with 2.7 unique controls on average, by gender and age rounded to the nearest integer. Measurements: Overall and stratified Reporting Odds Ratios (ROR) were calculated. Stratified contingency tables were tested for homogeneity using the Breslow-Day procedure, and Cochran-Mantel-Haenszel statistics were calculated to test the hypothesis of a ROR of unity. Results: 2,665 cases of anaphylaxis or anaphylactoid reactions and 7,125 controls of non-anaphylactic/anaphylactoid reports were compared. The ROR of an anaphylactic or anaphylactoid reaction was 1.325 (95% CI: 1.212 - 1.448, p < 0.001). The matched set of cases and controls did not reveal inhomogeneity by gender or age band strata, suggesting that these factors have no impact on the likelihood to report an anaphylactic event as opposed to a non-anaphylactic event following mRNA vaccination. A slightly elevated ROR was observed with patients who reported a history of allergic reactions to NSAIDs and/or fluoroquinolone antibiotics. The precise meaning and relevance of this finding remains to be elucidated. Previous reactions to vaccines do not appear to correlate statistically significantly with a higher risk of reporting an anaphylactic adverse effect after mRNA vaccination. Limitations: As a reporting study using data from VAERS, our analysis is subject to under- and overreporting, the extent of each of which is not known with any degree of precision. Since the Emergency Use Authorizations for both mRNA vaccines mandate reporting of all serious adverse events, reporting bias is likely in favour of non- mRNA vaccines, where such reporting is not mandatory in adults. Consequently, this analysis may exaggerate the ROR of anaphylactic and anaphylactoid events associated with mRNA vaccines, which may in reality be significantly lower. Conclusions: mRNA vaccination is not associated with a statistically significant higher risk of reporting an anaphylactic adverse event to VAERS. Anaphylaxis is a serious but very rare complication of all immunisations. No significant increase in reporting odds was found in any age group or gender, nor in most cases of previously known allergic adverse events in relation to vaccines. This study contributes to the growing body of evidence proving the safety and tolerability of mRNA vaccines.

Intravenous ondansetron induced hypersensitivity reaction: a case report

Ondansetron a selective 5-HT3 receptor antagonist has been widely used as a prophylactic antiemetic for chemotherapy induced and anaesthesia related nausea and vomiting. Anaphylaxis and anaphylactoid reaction rarely occur in less than 1% of the patients and may lead to potentially life-threatening events. This study is one such rare case report of hypersensitivity reaction to intravenous ondansetron in a perioperative setting. Familiarity about anaphylactoid reactions to intravenous ondansetron among the health practitioners would help them to bring about a rational approach to decrease its incidence.

Cardiac Arrest and Complications after Spinal Anesthesia: The Perioperative and Anesthetic Adverse Event in Thailand (PAAd Thai) Incident Report Study

Background: Spinal anesthesia is one of most common anesthetic techniques in Thailand. The Perioperative and Anesthetic Adverse Events in Thailand (PAAd Thai) Study was a multicentered project among 22 hospitals across the country to investigate the incidence of anesthesia related complications. Objective: To study the incidences of cardiac arrest and complication after spinal anesthesia including the contributing factors and suggested corrective strategies. Materials and Methods: This prospective descriptive study of the incident reports that occurred regarding spinal anesthesia collected from 22 participating hospital in the data collection between January and December of 2015 was completed. Three senior anesthesiologists reviewed the data and descriptive statistics were used. Results: Among 62,120 spinal anesthesia, there were 127 incidents (5.8%) among 2,206 incident reports related to anesthesia. There were seven cases of intraoperative cardiac arrest with an incidence of 1.13:10,000 spinal anesthesia (95% CI 0.55 to 2.33). Other complications were bradycardia with less than 40 beats per minute (50.4%), anaphylaxis or anaphylactoid reaction or drug allergy (14.2%), drug error (8.4%), coma or CVA or convulsion (3.9%), and suspected pulmonary embolism (3.9%). Adverse events occurred frequently with specialties or surgeries of orthopedics (44.1%), cesarean delivery (17.3%), urosurgery (17.3%), general surgery (14.2%), and gynecological surgery (4.7%), respectively. Conclusion: Contributing factors were inexperience, inappropriate decision making, haste, and inappropriate pre-anesthetic evaluation or preparation while factors minimizing incidents were vigilance, having experience, and experienced assistants. Suggested corrective strategies were quality assurance activity, guidelines especially monitoring, improvement of supervision, and additional training. Keywords: Spinal anesthesia, Adverse events, Incidents, Complications, Neuraxial anesthesia, Cardiac arrest

Macromolecular substances as a dangerous factor in traditional Chinese medicine injections were determined by size-exclusive chromatography

Macromolecular substances in traditional Chinese medicine injections (TCMIs) are expected to be a main dangerous factor causing anaphylactic or anaphylactoid reaction. The main aim of the study was to verify the macromolecular substances’ anaphylactic or anaphylactoid reaction in guinea pigs and establish a size-exclusive chromatographic method to detect them. The macromolecular substances from six TCMIs (Danshen injection, Dengzhanxixin injection, Honghua injection, Qingkailing injection, Shuanghuanglian injection and Shuxuening injection) were prepared by removing substances with molecular weight less than 10 kDa with an ultra-filter. The anaphylactic and anaphylactoid reactions caused by original TCMIs, injections rich in or free of macromolecules were assayed in guinea pigs. The relationship between the amount of the macromolecular substances and peak area of chromatogram was established by size-exclusive chromatography. Injections free of macromolecules were not likely to cause anaphylactic and anaphylactoid reactions, but injections rich in macromolecular substances were more likely to do so. If the macromolecular substances with molecular weight bigger than 10 kDa were removed, the signal of macromolecular substances in TCMIs was quantitatively reduced. All the results suggested that macromolecular substances in TCMIs are a dangerous factor causing safety problems, and the macromolecular substances can be quantitatively detected with size-exclusive chromatography.