Title: Fluid Responsiveness Evaluation in Sepsis-associated Hypotension (FRESH) Trial<br/>Author: Caleb Chan<br/><a href='http://umem.org/profiles/resident/1583/'>[Click to email author]</a><hr/><p class="p1" style="margin: 0px 0px 12px; font-variant-numeric: normal; font-variant-east-asian: normal; font-stretch: normal; line-height: normal; font-family: Arial; color: rgb(26, 26, 26); -webkit-text-stroke-color: rgb(26, 26, 26);">
<span class="s1" style="font-kerning: none;"><b>Clinical Question: </b>Will resuscitation guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes?</span></p>
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<span class="s1" style="font-kerning: none;"><b>Methodology:</b></span></p>
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<span class="s2" style="text-decoration-line: underline; font-kerning: none;">Design</span><span class="s1" style="font-kerning: none;">: Randomized, unblinded clinical trial among adults with sepsis-associated hypotension comparing PLR-guided SV responsiveness as a guide for fluid management (intervention) versus “usual care” at 13 hospitals in the United States and the United Kingdom (randomization was in a 2:1 allocation of SV-guided to usual care).</span></p>
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<span class="s2" style="text-decoration-line: underline; font-kerning: none;">Inclusion criteria</span><span class="s1" style="font-kerning: none;">:</span></p>
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<span class="s1" style="font-kerning: none;">-patients presenting to the ED with sepsis or septic shock and anticipated ICU admission.</span></p>
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<span class="s1" style="font-kerning: none;">-refractory hypotension (MAP ≤ 65mmHg after receiving ≥ 1L and < 3L of fluid)</span></p>
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<span class="s2" style="text-decoration-line: underline; font-kerning: none;">Exclusion criteria</span><span class="s1" style="font-kerning: none;">:</span></p>
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<span class="s1" style="font-kerning: none;">-infusion of > 3L of IV fluid prior to randomization</span></p>
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<span class="s1" style="font-kerning: none;">-hemodynamic instability due to active hemorrhage</span></p>
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<span class="s1" style="font-kerning: none;">-pregnancy or being incarcerated</span></p>
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<span class="s1" style="font-kerning: none;">-indication for immediate surgery</span></p>
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<span class="s1" style="font-kerning: none;">-acute CVA, acute coronary syndrome, acute pulmonary edema, status asthmaticus, major cardiac arrhythmia, drug overdose, injury from burn or trauma, status epilepticus</span></p>
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<span class="s1" style="font-kerning: none;">-inability or contraindication to passive leg raising</span></p>
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<span class="s2" style="text-decoration-line: underline; font-kerning: none;">Intervention (in ICU)</span><span class="s1" style="font-kerning: none;">:</span></p>
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<span class="s1" style="font-kerning: none;">-PLRs were performed prior to any treatment of hypoperfusion with either fluid bolus or vasopressors for the first 72 hours after ICU admission or until ICU discharge (whichever occurred first)</span></p>
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<span class="s1" style="font-kerning: none;">-If patient was FR (increase in SV ≥10%) a 500 ml crystalloid fluid bolus was given with repeat PLRs after every fluid bolus</span></p>
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<span class="s1" style="font-kerning: none;">-If the patient was non-FR, initiation or up-titration of vasopressors was prompted with repeat PLRs after significant escalation (an increase of 1 mcg/kg/min norepinephrine)</span></p>
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<span class="s1" style="font-kerning: none;"><b>Results:</b></span></p>
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<span class="s1" style="font-kerning: none;">-83 patients in Intervention arm, 41 in Usual Care arm</span></p>
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<span class="s1" style="font-kerning: none;"><b>-</b>Both arms received a similar volume of resuscitation fluid prior to enrollment (2.4 ± 0.6 L Intervention vs. 2.2 ± 0.7L Usual Care)</span></p>
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<span class="s1" style="font-kerning: none;">-Positive fluid balance at 72 hours or ICU discharge, was significantly less in the Intervention arm (-1.37L favoring Intervention, 0.65 ± 2.85L Median: 0.53L Intervention vs. 2.02 ± 3.44L Median: 1.22L Usual Care, p=0.02).</span></p>
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<span class="s1" style="font-kerning: none;">-Fewer patients required RRT (5.1% vs 17.5%, p=0.04) or MV in Intervention arm compared to Usual Care (17.7% vs 34.1%, p=0.04)</span></p>
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<span class="s1" style="font-kerning: none;">-ICU length of stay was similar in the two arms </span></p>
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<span class="s1" style="font-kerning: none;">-There was no difference in overall 30-day mortality (6.3% difference, Intervention: 15.7% vs. Usual Care: 22.0%, 95% CI -21.2%, 8.6%)</span></p>
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<span class="s1" style="font-kerning: none;"><b>Implications:</b></span></p>
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<span class="s1" style="font-kerning: none;">Although this is a smaller, unblinded (also funded by maker of SV monitoring device) study, Douglas et al. demonstrate that limiting fluid administration using dynamic assessments of fluid responsiveness to guide resuscitation in patients in septic shock is likely safe. In fact, this may actually decrease the need for renal replacement therapy and mechanical ventilation amongst this patient population. At the very least, this study adds to the body of literature showing the harms of excessive fluid administration and positive fluid balance.</span></p>
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<span class="s1" style="font-kerning: none;"><b>Bottom line:</b></span></p>
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<span class="s1" style="font-kerning: none;">If possible, use dynamic assessments of fluid responsiveness in patients with septic shock to guide interventions, particularly for further resuscitation beyond initial fluid resuscitation (~2 liters in this study).</span></p>
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<fieldset><legend>References</legend>
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Douglas IS, Alapat PM, Corl KA, et al. Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial. Chest. 2020</p>
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