Moderate IV Fluid Resuscitation Is Associated With Decreased Sepsis Mortality.

OBJECTIVES: Significant practice variation exists in the amount of resuscitative IV fluid given to patients with sepsis. Current research suggests equipoise between a tightly restrictive or more liberal strategy but data is lacking on a wider range of resuscitation practices. We sought to examine the relationship between a wide range of fluid resuscitation practices and sepsis mortality and then identify the primary driver of this practice variation. DESIGN: Retrospective analysis of the Premier Healthcare Database. SETTING: Six hundred twelve U.S. hospitals. PATIENTS: Patients with sepsis and septic shock admitted from the emergency department to the ICU from January 1, 2016, to December 31, 2019. INTERVENTIONS: The volume of resuscitative IV fluid administered before the end of hospital day- 1 and mortality. MEASUREMENTS AND MAIN RESULTS: In total, 190,682 patients with sepsis and septic shock were included in the analysis. Based upon patient characteristics and illness severity, we predicted that physicians should prescribe patients with sepsis a narrow mean range of IV fluid (95% range, 3.6-4.5 L). Instead, we observed wide variation in the mean IV fluids administered (95% range, 1.7-7.4 L). After splitting the patients into five groups based upon attending physician practice, we observed patients in the moderate group (4.0 L; interquartile range [IQR], 2.4-5.1 L) experienced a 2.5% reduction in risk-adjusted mortality compared with either the very low (1.6 L; IQR, 1.0-2.5 L) or very high (6.1 L; IQR, 4.0-9.0 L) fluid groups p < 0.01). An analysis of within- and between-hospital IV fluid resuscitation practices showed that physician variation within hospitals instead of practice differences between hospitals accounts for the observed variation. CONCLUSIONS: Individual physician practice drives excess variation in the amount of IV fluid given to patients with sepsis. A moderate approach to IV fluid resuscitation is associated with decreased sepsis mortality and should be tested in future randomized controlled trials.

Respiratory Variation in Carotid Artery Peak Systolic Velocity Is Unable to Predict Fluid Responsiveness in Spontaneously Breathing Critically Ill Patients When Assessed by Novice Physician Sonologists.

BACKGROUND: Respiratory variation in carotid artery peak systolic velocity (ΔVpeak) assessed by point-of-care ultrasound (POCUS) has been proposed as a noninvasive means to predict fluid responsiveness. We aimed to evaluate the ability of carotid ΔVpeak as assessed by novice physician sonologists to predict fluid responsiveness. METHODS: This study was conducted in 2 intensive care units. Spontaneously breathing, nonintubated patients with signs of volume depletion were included. Patients with atrial fibrillation/flutter, cardiogenic, obstructive or neurogenic shock, or those for whom further intravenous (IV) fluid administration would be harmful were excluded. Three novice physician sonologists were trained in POCUS assessment of carotid ΔVpeak. They assessed the carotid ΔVpeak in study participants prior to the administration of a 500 mL IV fluid bolus. Fluid responsiveness was defined as a ≥10% increase in cardiac index as measured using bioreactance. RESULTS: Eighty-six participants were enrolled, 50 (58.1%) were fluid responders. Carotid ΔVpeak performed poorly at predicting fluid responsiveness. Test characteristics for the optimum carotid ΔVpeak of 8.0% were: area under the receiver operating curve = 0.61 (95% CI: 0.48-0.73), sensitivity = 72.0% (95% CI: 58.3-82.56), specificity = 50.0% (95% CI: 34.5-65.5). CONCLUSIONS: Novice physician sonologists using POCUS are unable to predict fluid responsiveness using carotid ΔVpeak. Until further research identifies key limiting factors, clinicians should use caution directing IV fluid resuscitation using carotid ΔVpeak.

Change in Carotid Blood Flow and Carotid Corrected Flow Time Assessed by Novice Sonologists Fails to Determine Fluid Responsiveness in Spontaneously Breathing Intensive Care Unit Patients.

Measurement of carotid blood flow (CBF) and corrected carotid flow time (ccFT) has been proposed as a non-invasive means of determining fluid responsiveness. We evaluated the ability of CBF and ccFT as assessed by novice sonologists to determine fluid responsiveness in intensive care unit patients. Three novice physician sonologists performed carotid ultrasounds before and after a fluid bolus and calculated changes in CBF and ccFT. Fluid responsiveness was defined as a ≥10% increase in cardiac index as measured using bioreactance. Of 112 participants, 56 (50%) were fluid responders. Changes in CBF and ccFT performed poorly at determining fluid responsiveness: 19 mL/min (area under the receiver operating characteristic curve: 0.58, 95% confidence interval: 0.47-0.68) and 6 ms (0.59, 0.46-0.65) respectively. Novice physician sonologists are unable to determine fluid responsiveness using CBF or ccFT. Further research is needed to identify the key limiting factors in using carotid ultrasound to determine fluid responsiveness.

Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial.

BACKGROUND: Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume change during passive leg raise) to guide resuscitation and improve patient outcome. RESEARCH QUESTION: Will resuscitation that is guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes? STUDY DESIGN AND METHODS: We conducted a prospective, multicenter, randomized clinical trial at 13 hospitals in the United States and United Kingdom. Patients presented to EDs with sepsis that was associated hypotension and anticipated ICU admission. Intervention arm patients were assessed for fluid responsiveness before clinically driven fluid bolus or increase in vasopressors occurred. The protocol included reassessment and therapy as indicated by the passive leg raise result. The control arm received usual care. The primary clinical outcome was positive fluid balance at 72 hours or ICU discharge, whichever occurred first. RESULTS: In modified intent-to-treat analysis that included 83 intervention and 41 usual care eligible patients, fluid balance at 72 hours or ICU discharge was significantly lower (-1.37 L favoring the intervention arm; 0.65 ± 2.85 L intervention arm vs 2.02 ± 3.44 L usual care arm; P = .021. Fewer patients required renal replacement therapy (5.1% vs 17.5%; P = .04) or mechanical ventilation (17.7% vs 34.1%; P = .04) in the intervention arm compared with usual care. In the all-randomized intent-to-treat population (102 intervention, 48 usual care), there were no significant differences in safety signals. INTERPRETATION: Physiologically informed fluid and vasopressor resuscitation with the use of the passive leg raise-induced stroke volume change to guide management of septic shock is safe and demonstrated lower net fluid balance and reductions in the risk of renal and respiratory failure. Dynamic assessments to guide fluid administration may improve outcomes for patients with septic shock compared with usual care. CLINICAL TRIAL REGISTRATION: NCT02837731.

Delay in Antibiotic Administration Is Associated With Mortality Among Septic Shock Patients With Staphylococcus aureus Bacteremia.

OBJECTIVES: The relationship between the timing of antibiotics and mortality among septic shock patients has not been examined among patients specifically with Staphylococcus aureus bacteremia. DESIGN: Retrospective analysis of a Veterans Affairs S. aureus bacteremia database. SETTING: One-hundred twenty-two hospitals in the Veterans Affairs Health System. PATIENTS: Patients with septic shock and S. aureus bacteremia admitted directly from the emergency department to the ICU from January 1, 2003, to October 1, 2015, were evaluated. INTERVENTIONS: Time to appropriate antibiotic administration and 30-day mortality. MEASUREMENTS AND MAIN RESULTS: A total of 506 patients with S. aureus bacteremia and septic shock were included in the analysis. Thirty-day mortality was 78.1% for the entire cohort and was similar for those participants with methicillin-resistant S. aureus and methicillin-sensitive S. aureus bacteremia. Our multivariate analysis revealed that, as compared with those who received appropriate antibiotics within 1 hour after emergency department presentation, each additional hour that passed before appropriate antibiotics were administered produced an odds ratio of 1.11 (95% CI, 1.02-1.21) of mortality within 30 days. This odds increase equates to an average adjusted mortality increase of 1.3% (95% CI, 0.4-2.2%) for every hour that passes before antibiotics are administered. CONCLUSIONS: The results of this study further support the importance of prompt appropriate antibiotic administration for patients with septic shock. Physicians should consider acting quickly to administer antibiotics with S. aureus coverage to any patient suspected of having septic shock.

Performance of a 25% Inferior Vena Cava Collapsibility in Detecting Fluid Responsiveness When Assessed by Novice Versus Expert Physician Sonologists.

OBJECTIVES: Inferior vena cava collapsibility (cIVC) measured by point-of-care ultrasound (POCUS) has been proposed as a noninvasive means of assessing fluid responsiveness. We aimed to prospectively evaluate the performance of a 25% cIVC cutoff value to detect fluid responsiveness among spontaneously breathing intensive care unit (ICU) patients when assessed with POCUS by novice versus expert physician sonologists. METHODS: Prospective observational study of spontaneously breathing ICU patients. Fluid responsiveness was defined as a >10% increase in cardiac index following a 500 mL fluid bolus, measured by bioreactance. Novice sonologist measured cIVC with POCUS. Their measurements were later compared to an expert physician sonologist who independently reviewed the POCUS images and assessed cIVCs. RESULTS: Of the 85 participants, 44 (52%) were fluid responders. A 25% cIVC cutoff value performed better when assessed by expert sonologists than novice physician sonologists (receiver-operator characteristic curve, ROC = 0.82 [0.74-0.88] vs ROC = 0.69 [0.60-0.77]). CONCLUSIONS: A 25% cIVC cutoff value measured by POCUS detects fluid responsiveness. However, the experience of the physician sonologist affects test performance and should be considered when interpreting and clinically using cIVC to direct intravenous fluid resuscitation.

The Restrictive IV Fluid Trial in Severe Sepsis and Septic Shock (RIFTS): A Randomized Pilot Study.

OBJECTIVES: It is unclear if a low- or high-volume IV fluid resuscitation strategy is better for patients with severe sepsis and septic shock. DESIGN: Prospective randomized controlled trial. SETTING: Two adult acute care hospitals within a single academic system. PATIENTS: Patients with severe sepsis and septic shock admitted from the emergency department to the ICU from November 2016 to February 2018. INTERVENTIONS: Patients were randomly assigned to a restrictive IV fluid resuscitation strategy (≤ 60 mL/kg of IV fluid) or usual care for the first 72 hours of care. MEASUREMENTS AND MAIN RESULTS: We enrolled 109 patients, of whom 55 were assigned to the restrictive resuscitation group and 54 to the usual care group. The restrictive group received significantly less resuscitative IV fluid than the usual care group (47.1 vs 61.1 mL/kg; p = 0.01) over 72 hours. By 30 days, there were 12 deaths (21.8%) in the restrictive group and 12 deaths (22.2%) in the usual care group (odds ratio, 1.02; 95% CI, 0.41-2.53). There were no differences between groups in the rate of new organ failure, hospital or ICU length of stay, or serious adverse events. CONCLUSIONS: This pilot study demonstrates that a restrictive resuscitation strategy can successfully reduce the amount of IV fluid administered to patients with severe sepsis and septic shock compared with usual care. Although limited by the sample size, we observed no increase in mortality, organ failure, or adverse events. These findings further support that a restrictive IV fluid strategy should be explored in a larger multicenter trial.

A modified Montpellier protocol for intubating intensive care unit patients is associated with an increase in first-pass intubation success and fewer complications.

BACKGROUND: The Montpellier protocol for intubating patients in the intensive care unit (ICU) is associated with a decrease in intubation-related complications. We sought to determine if implementation of a simplified version of the Montpellier protocol that removed selected components and allowed for a variety of pre-oxygenation modalities increased first-pass intubation success and reduced intubation-related complications. METHODS: A prospective pre/post-comparison of a modified Montpellier protocol in two medical and one medical/surgical/cardiac ICU within a hospital system. The modified eight-point protocol included: fluid administration, ordering sedation, two intubation trained providers, pre-oxygenation with non-invasive positive pressure ventilation, nasal high flow cannula or non-rebreather mask, rapid sequence intubation, capnography, sedation administration, and vasopressors for shock. RESULTS: Patient characteristics and indications for intubation were similar for the 275 intubations in the control (137) and intervention (138) periods. In the intervention vs. control periods, the modified Montpellier protocol was associated with a significant 16.2% [95% CI: 5.1-30.0%] increase in first-pass intubation success and a 12.6% [95% CI: 1.2-23.6%] reduction in all intubation-related complications. CONCLUSION: A simplified version of the Montpellier intubation protocol for intubating ICU patients was associated with an improvement in first-pass intubation success rates and a reduction in the rate of intubation-related complications.

Inferior vena cava collapsibility detects fluid responsiveness among spontaneously breathing critically-ill patients.

PURPOSE: Measurement of inferior vena cava collapsibility (cIVC) by point-of-care ultrasound (POCUS) has been proposed as a viable, non-invasive means of assessing fluid responsiveness. We aimed to determine the ability of cIVC to identify patients who will respond to additional intravenous fluid (IVF) administration among spontaneously breathing critically-ill patients. METHODS: Prospective observational trial of spontaneously breathing critically-ill patients. cIVC was obtained 3cm caudal from the right atrium and IVC junction using POCUS. Fluid responsiveness was defined as a≥10% increase in cardiac index following a 500ml IVF bolus; measured using bioreactance (NICOM™, Cheetah Medical). cIVC was compared with fluid responsiveness and a cIVC optimal value was identified. RESULTS: Of the 124 participants, 49% were fluid responders. cIVC was able to detect fluid responsiveness: AUC=0.84 [0.76, 0.91]. The optimum cutoff point for cIVC was identified as 25% (LR+ 4.56 [2.72, 7.66], LR- 0.16 [0.08, 0.31]). A cIVC of 25% produced a lower misclassification rate (16.1%) for determining fluid responsiveness than the previous suggested cutoff values of 40% (34.7%). CONCLUSION: IVC collapsibility, as measured by POCUS, performs well in distinguishing fluid responders from non-responders, and may be used to guide IVF resuscitation among spontaneously breathing critically-ill patients.