Study Retrieval and Selection

Figure 1 illustrates the flow diagram for the study retrieval and selection process. Supplementary Information 4 presents a list of studies excluded after a full-text review. The literature was searched between May 18 and 25, 2022, and the search was performed again between August 13 and 15, 2023 when finalizing this review. A total of 1,993 articles were identified, and 21 SRs were eligible for this review [9, 13, 16, 17, 23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39].

Fig. 1

Flow diagram for the study retrieval and selection process

Study Quality

Table 1 summarizes the AMSTAR 2 results of the 21 eligible SRs. The AMSTAR 2 assessment revealed that only 1 SR had high quality [13], 11 had low quality [9, 16, 17, 26, 28, 33,34,35, 37,38,39], and 9 had critically low quality [23,24,25, 27, 29,30,31,32, 36]. To ensure the quality of evidence, we excluded the SRs with critically low quality. Subsequently, 12 SRs [9, 13, 16, 17, 26, 28, 33,34,35, 37,38,39] were included in this review. Despite the exclusion of the SRs with critically low quality, the included SRs covered all 16 original studies [40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55]. Notably, the included SRs indicated that most of the original studies had a low RoB [9, 13, 16, 17, 26, 28, 33,34,35, 37,38,39].

Table 1 AMSTAR 2 results of the eligible systematic reviewsStudy Characteristics

Table 2 presents the characteristics of the included SRs, and Table 3 lists the original studies reviewed in each SR. It is necessary to mention that all drugs were administered intravenously. Vasopressin was administered at a dosage of 40 IU per CPR cycle (1 dose or 2 doses) for a comparison of vasopressin alone or vasopressin–epinephrine with epinephrine alone and at a dosage of 20 IU per CPR cycle (4–5 doses) for a comparison of VSE with epinephrine–placebo. Epinephrine was administered at a dosage of 1 mg per CPR cycle. Methylprednisolone was administered at a dosage of 40 mg during CPR with or without hydrocortisone administered at a dosage of 300 mg for 7 days [9, 13, 16, 17, 26, 28, 33,34,35, 37,38,39].

Table 2 Characteristics of the included systematic reviewsTable 3 Original studies reviewed in each systematic reviewOutcome Evaluation

Table 4 presents the results of the pairwise meta-analyses performed in the included SRs.

Table 4 Results of the pairwise meta-analyses performed in the included systematic reviewsReturn of Spontaneous Circulation Vasopressin Alone Versus Epinephrine Alone

Finn et al. [13] performed three pairwise meta-analyses to compare vasopressin alone and epinephrine alone in terms of their effects on ROSC. They discovered no significant difference in ROSC among patients with IHCA (risk ratio [RR], 1.76; 95% CI, 0.40–7.71; p = 0.45), those with OHCA (RR, 1.05; 95% CI, 0.80–1.39; p = 0.72), and those with IHCA or OHCA (RR, 1.10; 95% CI, 0.90–1.33; p = 0.36).

Vasopressin–Epinephrine Versus Epinephrine Alone

Three pairwise meta-analyses were performed to compare vasopressin–epinephrine and epinephrine alone in terms of their effects on ROSC [13, 34, 38]. Zhang et al. [38] reported a significant increase in ROSC in patients with OHCA receiving vasopressin–epinephrine compared with that in those receiving epinephrine alone (OR, 1.67; 95% CI, 1.13–2.49; p = 0.01). By contrast, no significant difference was observed in ROSC among patients with OHCA in the meta-analyses conducted by Finn et al. [13] (RR, 0.97; 95% CI, 0.87–1.08; p = 0.57) and Lin et al. [34] (RR, 0.96; 95% CI, 0.89–1.04; p = 0.31). Sillberg et al. [37] narratively described the results of two RCTs [41, 53], which were included in the aforementioned meta-analyses.

No pairwise meta-analysis included all RCTs. Three RCTs [41,42,43] were common among the meta-analyses performed by Finn et al. [13], Lin et al. [34], and Zhang et al. [38]. Furthermore, two RCTs [51,