Although setting a target for blood pressure is a common treatment strategy for critically ill patients with shock, the target blood pressure for vasodilatory shock remains controversial. In addition, the optimal blood pressure control target according to the patient’s background, such as older age or a history of cardiovascular disease, has not been sufficiently studied.
To our best knowledge, this meta-analysis of optimal blood pressure control for vasodilatory shock allowed for the largest sample size, which is expected to be more representative of the patient population, leading to more accurate results. Also, it is meaningful to re-examine the subgroup analyses which showed conflicting results in previous RCTs.
This meta-analysis of three trials comparing a higher MAP target group with a lower MAP target group showed no significant difference in all-cause mortality. In the subgroup analysis for patients with chronic hypertension and even in patients aged ≥ 65 years, the intervention for the higher MAP target did not significantly improve mortality compared to the lower MAP target.
The results of the mortality rate comparing the higher and lower MAP groups were consistent with those of the three integrated trials[10, 11, 16]. There is little evidence that higher blood pressure control improves mortality rate. This is supported by the finding that there was no difference in mortality in the subgroup analysis of patients with chronic hypertension and older adults. Although there was no difference in serious adverse events associated with vasopressors between the two groups, the incidence of supraventricular arrhythmia was significantly higher in the higher MAP group. Refraining from excessive blood pressure control with vasopressors may reduce adverse events, such as arrhythmias. For these reasons, patient management with an MAP maintained at a value greater than 65 mmHg is not routinely recommended in patients with vasodilatory shock. The Surviving Sepsis Campaign guideline 2021 also supports this result . On the other hand, there was no discussion regarding personalized blood pressure control targets based on individual patient medical history, such as cardiovascular diseases and chronic hypertension.
Regarding the use of renal replacement therapy in patients with chronic hypertension, on the one hand, the SEPSISPAM trial showed a significantly lower use in the high MAP target group. In contrast, the 65 trial showed no significant difference in renal replacement therapy between the high-and low-MAP target groups. Performing the integrated analysis of these two RCTs, the higher MAP target group showed lower use of renal replacement therapy in patients with chronic hypertension. A previous study reported that patients with chronic hypertension are required to have a higher MAP than those without chronic hypertension in order to maintain renal blood flow. Therefore, management of a higher MAP target can be helpful from the perspective of renal protection. In fact, the actual MAP in the higher target group of SEPSISPAM was the highest (85–90 mmHg) among the three RCTs, which may be associated with a reduction in renal replacement therapy. In addition, a previous prospective study suggested that management with a higher MAP target of 72–82 mmHg was needed to avoid acute kidney insufficiency (AKI). However, this result is based on a subgroup analysis that needs to be interpreted carefully.
The present meta-analysis evaluated RCTs of vasodilatory shock patients; however, there might be differences in the pathophysiology between septic shock and other vasodilatory shocks. Patients with septic shock generally demonstrate increased oxygen demand due to systemic hypermetabolism, whereas a similar increase in oxygen demand does not occur in patients after general anesthesia or in patients with spinal cord injury. Thus, patients with septic shock may require more stringent blood pressure control to meet the oxygen demands of each organ. In this regard, it should be noted that, although the 65 trial included a large number of patients with vasodilatory shock, which may have affected the results of the present meta-analysis, the proportion of patients with septic shock in the trial was less than half. Regarding the optimal blood pressure target in septic shock patients with chronic hypertension, the results of an ongoing RCT (UMIN000041775) will provide further important insights into this topic.
This study has several limitations. First, the actual MAP in the lower MAP group exceeded the target blood pressure values defined in each trial, and each actual blood pressure value differed by trial. Second, we did not obtain sufficient data regarding mortality and secondary outcomes according to the specific subgroups in each trial. Therefore, we could not evaluate them individually based on the patient’s background. Finally, the evidence obtained in this analysis may be helpful for older adults, as 92.1% of patients enrolled in this analysis were over 65 years old; thus, the generalizability of our findings may be limited because of the relatively smaller proportion of younger patients.