To the Editor,
Anaphylaxis is a life‐threatening clinical emergency, and prompt intramuscular (IM) injection of epinephrine is critical.11, 22, 33 Current practices pertaining to the initial treatment of anaphylaxis in China remain unclear. In this study, we assessed the actual initial treatment and the use of epinephrine for anaphylaxis in China by systematic analysis of published case reports between 2014 and 2018.
An online literature search was performed in PubMed, Web of Science, ScienceDirect, China National Knowledge Internet database (http://www.cnki.net), Wanfang database (http://med.wanfangdata.com.cn), and VIP database (http://www.cqvip.com). The following key words were used: “anaphylaxis,” “anaphylactic reactions,” “anaphylactic reaction,” “anaphylactic shock,” “reactions, anaphylactic,” “reaction, anaphylactic,” “shock, anaphylactic,” “kounis,” “kounis syndrome,” and “china”. The inclusion criteria were as follows: (a) diagnosis of anaphylaxis11; (b) availability of records about the anaphylaxis; (c) published from January 1, 2014, to December 31, 2018; (d) published in English or Chinese. Exclusion criteria were as follows: (a) cases with incomplete data; (b) duplicate publication; (c) cases in which cardiac arrest occurred prior to the administration of epinephrine. Overdose of epinephrine was defined as administration of a dose that exceeded the dose recommended by the guidelines. 22, 33, 44
A total of 7579 articles were retrieved on database search, and a total of 819 patients from 748 case reports were included in this review (Figure S1). These patients were distributed across 30/31 (96.8%) provinces in mainland China except Tibet (Figure S2). Patient characteristics are summarized in Table S1. The median age was 46.1 years, and 53.0% patients were male. More than 2/3rd of the episodes of anaphylaxis occurred among inpatients. All the patients except one (99.9%) presented severe anaphylactic reactions (cardiovascular and/or respiratory compromise). The mortality rate was 5.6%.
Removal of the likely trigger (57.3%) and supplemental oxygen (42.1%) were the 2 most commonly administered initial treatment followed by glucocorticoids (19.8%) and intravenous (IV) fluid support (14.9%; Table 1). Only 14.2% patients were appropriately treated with epinephrine as the first‐line intervention. The percentage of patients treated with glucocorticoids was significantly higher than the percentage of those treated with epinephrine as the first‐line treatment (19.8% vs. 14.2%; P < .001), as the first‐line medication (44.3% vs. 38.5%, P = .016), or during the course of anaphylaxis (94.7% vs. 70.8%, P < .001).
|Patients with available data, n||Value|
|First‐line treatment, n (%)|
|Removal of the trigger||819||469 (57.3)|
|Calcium gluconate||819||4 (0.5)|
|First‐line medication, n (%)|
|Calcium gluconate||819||7 (0.9)|
|Respiratory stimulant||819||4 (0.5)|
|No medication||819||1 (0.1)|
|Treatment during the course of anaphylaxis, n (%)|
|Nasal catheter||648||484 (74.7)|
|Face mask||648||82 (12.7)|
|Endotracheal intubation||648||77 (11.9)|
|Noninvasive ventilator||648||3 (0.5)|
|Fluid support||819||583 (71.2)|
|Normal saline||583||229 (39.3)|
|Glucose solution||583||83 (14.2)|
|Balanced solution||583||71 (12.2)|
|Colloid solution||583||64 (11.0)|
|Glucose saline||583||17 (2.9)|
|TCM solution||583||1 (0.2)|
|50% Glucose solution||583||1 (0.2)|
|Inhaled beta‐2 agonists||819||10 (1.2)|
|Administration of epinephrine in patients with available data|
|Dosage (mg)||Route (n)||Overdose (n)|
|IM||SC||IV injection||IV infusion||Intra‐tracheal||unspecified||Total (n)|
Among children, the two most commonly administered initial doses of epinephrine were 0.3 mg (28.6%) and 0.5 mg (26.5%), and the two most common routes of administration were IV bolus injection (41.2%) and subcutaneous (SC) injection (41.2%). Only seven children (13.7%) received epinephrine by IM route. Most (89.4%) of children were administered an initial overdose of epinephrine. The percentage of children who received epinephrine overdose by IV bolus injection, SC injection, and IM injection was 100.0%, 73.7%, and 71.4%, respectively.
Among adult patients, the percentage of patients who received an initial dose of 1.0 mg (62.5%) was significantly higher than the percentage of those who received 0.5 mg (24.0%; P < .001). The percentage of patients who received epinephrine via IM injection (16.3%) was significantly lower than those who received IV bolus (46.0%, P < .001) or SC injection (36.1%, P < .001). Out of the 476 patients for whom the records of the epinephrine dose and the route of administration were available, 385 (80.9%) patients received an initial overdose of epinephrine. The percentage of overdose was more common with IV bolus injection (99.5%) as compared to IM injection (63.0%; P < .001) or SC injection (65.5%; P < .001).
Out of 580 patients who received epinephrine, 54 (9.3%) developed serious adverse effects associated with epinephrine (Table S2), including ventricular arrhythmias (59.3%), hypertension (20.4%), pulmonary edema (13.0%), myocardial ischemia (5.6%), and stroke (1.9%). Among the 52 patients with complete records of both the dose and route of administration of epinephrine, 50 (96.2%) patients had received an overdose and 45 (86.5%) were administered epinephrine by IV bolus injection.
To the best of our knowledge, this is the first study that evaluated the actual initial treatment of anaphylaxis in China based on a literature review. Due to the space limitation, only four of the 748 studies included in this review were referenced. Our results indicated considerable underuse of epinephrine as the initial treatment of anaphylaxis. In contrast, glucocorticoids were inappropriately used as the first‐line drug in place of epinephrine. Moreover, 81.6% patients had received an overdose of epinephrine, and 45.5% patients received IV bolus injection, both of which were proved to be significantly associated with serious adverse effects of epinephrine. Our findings suggest that the actual initial treatment of anaphylaxis in China does not comply with the international anaphylaxis guidelines. Of note, none of these problems was discussed or mentioned in these reports. This implies a general lack of awareness about the gaps in the initial treatment of anaphylaxis among many Chinese healthcare professionals.99 Our findings call for concerted efforts to remedify the current situation and to promote the safety of Chinese patients with anaphylaxis.
The study has a selection bias because the cases come from published reports. However, a large enough sample size helped negate this limitation to a certain extent. We established rigorous inclusion/exclusion criteria to minimize the risk of bias, and a thorough literature search was performed to include more cases of anaphylaxis. Moreover, Inclusion of Chinese literature helped increase the yield of cases and improved the representativeness of our findings.
Our study highlights some critical gaps in the initial treatment of anaphylaxis in China when compared against the international guidelines. Underuse, overdose, and inappropriate route of administration of epinephrine, as well as overuse of glucocorticoids, are the major problems. The epinephrine overdose and administration of IV bolus injection significantly increase the risk of serious adverse effects of epinephrine. Targeted training on the initial treatment of anaphylaxis is strongly suggested for healthcare providers in China.