DOES EARLY VASOPRESSOR USE IN SEPSIS RESULT IN BETTER OUTCOMES? A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

TOPIC: Critical Care TYPE: Original Investigations PURPOSE: Advancements in the management of septic shock have been significant over the past decade, however mortality rates still remain high. The latest sepsis guidelines recommend aggressive fluid therapy followed by vasopressor use in persistently hypotensive patients. The exact timing of vasopressor initiation remains unknown. Recent data suggests that there may be more benefit in starting vasoactive agents earlier or simultaneously along with the fluid of choice. Therefore, we conducted a meta-analysis to evaluate the effect of early versus late vasopressor use on clinical outcomes in septic shock patients. METHODS: PubMed, Cochrane, and Embase databases were searched systematically for studies that compared early versus late vasopressor initiation in septic shock patients and reported our pre-defined primary outcome of short-term mortality. Other inclusion criteria included administration of vasopressors within a 6-hour (h) window, minimum 2 group comparison, > 50 patients, and suffering from septic shock. Study selection, data extraction, and evaluation were performed by two investigators independently. Secondary outcomes that were collected included ICU length of stay, hospital length of stay, the volume of intravenous fluids within the first 6 hours, and time to achieved target mean arterial pressure (≥ 65 mmHg). RESULTS: Of the 601 articles identified, 48 underwent full-text screening and 7 articles with a total of 1,867 patients were included in the meta-analysis. Early vasopressor initiation resulted in decreased short term mortality compared to late vasopressor administration (odds ratio [OR] = 0.54; 95% CI,0.4 to 0.713; P < 0.001; I2 = 30.28%). Secondary outcomes showed time (in hours) to achieve target MAP of 65mmHg was shorter in the early vasopressor group (mean difference: − 1.15; 95% CI, − 1.37 to -0.92; P = <0.001; I2 = 44.58%). There was no difference in ICU length of stay (mean difference = − 0.42; 95% CI, − 0.18 to 1.01; I2 = 86.52%), hospital length of stay (mean difference = − 1.29; 95% CI, − 0.54 to 3.12; I2 = 91.94%), or net fluids in first 6 hours (mean difference = − 295.08; 95% CI, − 717.74 to 127.58; I2 = 97.77%) between the two groups, respectively. CONCLUSIONS: The use of early vasopressors in septic shock patients decreased short-term mortality and time to target MAP of ≥ 65 mmHg. However, no statistically significant difference was shown for hospital length of stay, ICU length of stay, or total net fluids required within the first 6 hours. Further randomized controlled trials are warranted to better address the study question. CLINICAL IMPLICATIONS: Early vasopressor initiation in septic shock patients appears to benefit mortality outcomes. This approach to septic shock management may potentially limit the complications of aggressive fluid resuscitation. These results will encourage clinicians to not delay vasoactive agents use in favor of extensive fluid resuscitation and consequently minimize delays in hypotension correction. DISCLOSURES: No relevant relationships by Tewodros Eguale, source=Web Response No relevant relationships by Mohammad Ghanbar, source=Web Response No relevant relationships by Ethar Makhseed, source=Web Response