Title: To Start Or Not To Start Vasopressor????<br/>
Author: Quincy Tran<br/>
<a href='mailto:qtran@som.umaryland.edu'>[Click to email author]</a><hr/>
Link: <a href='https://umem.org/educational_pearls/4385/'>https://umem.org/educational_pearls/4385/</a><hr/><p><strong>Settings</strong>: systemic review and meta-analysis</p>
<p><strong>Participants</strong>: 2 RCTs, 21 observational studies. Fifteen studies were published between 2020-2023.</p>
<p>There was a total of 25721 patients with septic shock</p>
<p><strong>Outcome measurement</strong>: Primary outcome was short-term mortality (ICU, hospital, 28-day, 30-day). Secondary outcomes included ICU LOS, Hospital LOS, time to achieve MAP > 65 mm Hg,</p>
<p><strong>Study Results</strong>:</p>
<p><em>Composite outcome of short term mortality</em>: </p>
<ul>
<li>20 studies and 17470 patients. Early initiation of vasopressors was associated with lower odds of short term mortality (OR 0.775, 95% CI 0.673-0.893, P<0.001, I2 = 68%).</li>
<li>Early initiation of norepinephrine was associated with lower odds of short term mortality (OR 0.656, 95% CI = 0.544 to 0.790, P <0.001, I2 = 57.2%)</li>
<li>Early initiation of vasopressin was also associated with lower odds of short term mortality (OR 0.685, 95% CI 0.558-0.840, P < 0.001, I2= 57%)</li>
</ul>
<p> <em>Secondary outcome</em>:</p>
<ul>
<li>Early vasopressor group was associated with lower odds of <em>RRT use</em> (OR 0.796, 95% CI 0.654-0.968, P = 0.022, I2 = 0%)</li>
<li>
<em>Mean Serum lactate levels at 6 hours</em> was similar in early vasopressor group (Mean Difference 0.218, 95% CI -0.642 to 1.079, P = 0.619).</li>
<li>However, <em>mean serum lactate levels at 6 hours</em> was lower in early norepinephrine subgroup (mean difference -0.489, 95% CI -0.863 to -0.115, P = 0.01).</li>
</ul>
<p><strong>Discussion</strong>:</p>
<ul>
<li>This appears to be a hot topic. When our group did this topic in 2020, there were 8 or 9 studies. Since 2020, there has been a significant increase in the number of publications, although most publications were observation studies.</li>
<li>Early initiation of norepinephrine may reduce fluid overload, not by reducing fluid input, but by improving host inflammatory response, improving endothelial cell barrier stability.</li>
<li>Counter-intuitively, early vasopressor was also found to be associated with lower incidence of arrhythmia, which the authors attributed to shorter duration of vasopressors and lower total dosage.</li>
</ul>
<p><strong>Conclusion</strong>: </p>
<p>More and more studies, although a RCT is still necessary, are showing that early initiation of vasopressor within 1-6 hours of septic shock would be more beneficial to patients with septic shock.</p>
<fieldset><legend>References</legend><p>Ye E, Ye H, Wang S, Fang X. INITIATION TIMING OF VASOPRESSOR IN PATIENTS WITH SEPTIC SHOCK: A SYSTEMATIC REVIEW AND META-ANALYSIS. Shock. 2023 Nov 1;60(5):627-636. doi: 10.1097/SHK.0000000000002214. Epub 2023 Sep 2. PMID: 37695641.</p>
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