A Systematic Review and Meta-Analysis of the Timing of Vasopressor Therapy in Patients with Septic Shock: Assessing Clinical Outcomes and Implication

Abstract Background Septic shock, the most severe form of sepsis, is associated with a high mortality rate and increased expenses. Therefore, updating the guidelines for its management can aid in minimizing mortality and expenses. Currently, the first-line therapy for septic shock entails administering resuscitation fluids followed by infusing vasopressors when the blood pressure goal is not achieved. The recommended first-line vasopressor is norepinephrine, followed by vasopressin, epinephrine, angiotensin II, and dopamine. Although the research has shown the efficacy of these vasopressors in different subsets of septic shock patients, there is still a controversy on when they should be administered. Therefore, we conducted the present review to determine the impact and implications of vasopressor timing in septic shock patients. Methods PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar databases were comprehensively searched for potential studies until October 2023. The methodological quality and bias assessment of valid records was examined with the Newcastle Ottawa Scale and Cochrane’s risk of bias tool. Additionally, all the meta-analyses were performed with Review Manager software. Results Twelve articles were eligible for review and analysis. Pooled analyses of data from 7 of these studies demonstrated a significantly lower incidence of mortality and shorter duration to achieve target mean arterial pressure (MAP) in the early norepinephrine group than in the late group (OR: 0.44; 95% CI: 0.35 – 0.55; p<0.00001 and MD: -1.17; 95% CI: -2.00 – -0.34; p = 0.0006). However, the length of ICU stay did not differ between the early and late norepinephrine group (MD: 0.55; 95% CI: -0.52 – 1.62; p = 0.31). On the other hand, the subgroup analyses show that early vasopressin is associated with a decreased mortality than late administration (OR: 0.60; 95% CI: 0.41 – 0.90; p = 0.01). Similarly, the pooled analysis has shown that early concomitant administration of vasopressin and norepinephrine is associated with a shorter duration to achieve target MAP than norepinephrine alone (MD: -3.15; 95% CI: -4.40 – -1.90; p <0.00001). Conclusion Early administration of norepinephrine has a mortality benefit and improves the duration taken to attain and sustain the goal MAP. Furthermore, early vasopressin possesses the potential to lower the fatality rate in individuals experiencing septic shock. However, further research is required to validate this finding.