Efficacy And Safety Of Four Kinds Of Glucocorticoids In The Adjunctive Treatment Of Severe Community-Acquired Pneumonia In Adults:a Network Meta-Analysis

Background : Community-acquired pneumonia is a common clinical infectious disease with high prevalence and mortality.Glucocorticoids can benefit some adults with severe community-acquired pneumonia,but they can also cause serious side effects such as hyperglycemia,gastrointestinal bleeding,delayed pathogen clearance,hypoadrenocorticism,femoral head necrosis,Osteonecrosis of femoral head and so on.Therefore,whether glucocorticoids are routinely used as adjuvant therapy for severe community-acquired pneumonia in adults remains controversial.For this reason,how to choose glucocorticoids and which kinds of glucocorticoids is more suitable for patients is particularly important.The purpose of this article is to compare and rank the efficacy and safety of four kinds of glucocorticoids in adjuvant treatment of severe community-acquired pneumonia in adults through network meta-analysis.Methods: We conducted direct meta-analysis and network meta-analysis.Three databases of Pub Med,EMBASE and Cochrane Library were searched for related studies published in English up to September,2019.Randomized controlled trials(RCTs)of glucocorticoids in adults with severe communityacquired pneumonia were included,and two persons independent extracted relevant information and data from those RCTs.We included and evaluated four kinds of glucocorticoids(hydrocortisone,methylprednisolone,prednisone,dexamethasone)for severe community-acquired pneumonia in adults.We included incomplete data experiments and failure to clearly indicate glucocorticoids type as well as experiments involving patients with immunodeficiency.The Cochrane Collaboration’s Risk of Bias Tool was used to assess the quality of all included RCTs.We used direct meta-analysis and network meta-analysis to evaluate the efficacy(mortality,the length of ICU stay,the length of hospital stay)and safety(gastrointestinal bleeding rate)of each intervention,and used Review Manager 5.3 and Stata 15.0 for statistical analysis.Results: A total of 11 RCTs and 1,235 patients were included in the study.Efficacy:(1).Direct meta-analysis results showed that compared with placebo +conventional treatment group,hydrocortisone + conventional treatment group can significantly reduce the patient’s mortality rate(OR=0.233,95% CI:0.104 to0.518,P=0);Compared with placebo + conventional treatment group,hydrocortisone + conventional treatment group(SMD=-0.688,95% CI:-1.185 to-0.191,P=0.007)and methylprednisolone + conventional treatment group(SMD=-0.330,95% CI:-0.637 to-0.022,P=0.036)can shorten the length of intensive care unit(ICU)stay.In terms of the length of hospital stay,the differences between the four kinds of glucocorticoid treatment groups and placebo treatment group were not statistically significant.(2).Network meta-analysis results: in terms of mortality,the length of ICU stay,and the length of hospital stay,the network evidence plots are all star-shaped structure plots centered on the placebo treatment group.The ranking of network meta analysis results was sorted by the results of the surface under the cumulative ranking(SUCRA).In terms of mortality,the higher the SUCRA value,the lower the mortality.The rankings were hydrocortisone + conventional treatment group(SUCRA = 98.0),methylprednisolone + conventional treatment group(59.0),dexamethasone +conventional treatment group(32.0),placebo + conventional treatment group(31.1),Prednisone + conventional treatment group(29.0).In terms of shortening the total length of hospital stay,the higher the SUCRA value,the shorter the total length of hospital stay.The rankings were hydrocortisone + conventional treatment group(85.2),prednisone + conventional treatment group(57.5),dexamethasone + conventional treatment group(41.7),methylprednisolone +conventional treatment group(36.5),placebo + Conventional treatment group(29.1).In terms of shortening the length of ICU stay,the higher the SUCRA value,the shorter the ICU duration.The rankings were hydrocortisone +conventional treatment group(95.6),prednisolone + conventional treatment group(68.8),placebo + conventional treatment group(34.8),dexamethasone +conventional treatment group(0.8).Safety:(1).direct meta-analysis results showed that in terms of gastrointestinal bleeding rate,the difference between hydrocortisone + conventional treatment group(OR=0.81,95% CI:0.228 to 2.883,P=0.745)and methylprednisolone + conventional treatment group(OR=0.962,95%CI:0.132 to 6.993,P=0.97)vs placebo + conventional treatment group was not statistically significant.(2).The results of the network meta-analysis showed that according to their SUCRA results,the higher the value,the lower the gastrointestinal bleeding rate.The order of the four interventions was hydrocortisone + conventional treatment group(66),methylprednisolone +conventional treatment group(55.1),placebo + conventional treatment group(53.2),Dexamethasone + conventional treatment group(25.7).Conclusion: Four kinds of glucocorticoids in the adjunctive treatment of severe community-acquired pneumonia in adults,of which hydrocortisone has the lowest mortality rate and the shortest length of hospital stay.Among hydrocortisone,methylprednisolone and dexamethasone,hydrocortisone has the shortest length of ICU stay and the lowest gastrointestinal bleeding rate.Systemic use of hydrocortisone may be the best initial option for adjuvant treatment of severe community-acquired pneumonia in adults.