Fluid Therapy and Acute Respiratory Distress Syndrome.

The optimal fluid management for acute respiratory distress syndrome (ARDS) remains unknown. Liberal fluid management may improve cardiac function and end-organ perfusion, but may lead to increased pulmonary edema and inhibit gas exchange. Trials suggest that conservative fluid management leads to better clinical outcomes, although prospective randomized, controlled trials have not demonstrated mortality benefit. Recent discoveries suggest there is large heterogeneity in ARDS, and varying phenotypes of ARDS respond differently to fluid treatments. Future advances in management will require real-time assignment of ARDS phenotypes, which may facilitate inclusion into clinical trials by ARDS phenotype and guide development of targeted therapies.

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.

Development of a Deep Learning Network to Classify Inferior Vena Cava Collapse to Predict Fluid Responsiveness.

OBJECTIVES: To create a deep learning algorithm capable of video classification, using a long short-term memory (LSTM) network, to analyze collapsibility of the inferior vena cava (IVC) to predict fluid responsiveness in critically ill patients. METHODS: We used a data set of IVC ultrasound (US) videos to train the LSTM network. The data set was created from IVC US videos of spontaneously breathing critically ill patients undergoing intravenous fluid resuscitation as part of 2 prior prospective studies. We randomly selected 90% of the IVC videos to train the LSTM network and 10% of the videos to test the LSTM network's ability to predict fluid responsiveness. Fluid responsiveness was defined as a greater than 10% increase in the cardiac index after a 500-mL fluid bolus, as measured by bioreactance. RESULTS: We analyzed 211 videos from 175 critically ill patients: 191 to train the LSTM network and 20 to test it. Using standard data augmentation techniques, we increased our sample size from 191 to 3820 videos. Of the 175 patients, 91 (52%) were fluid responders. The LSTM network was able to predict fluid responsiveness moderately well, with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval [CI], 0.43-1.00), a positive likelihood ratio of infinity, and a negative likelihood ratio of 0.3 (95% CI, 0.12-0.77). In comparison, point-of-care US experts using video review offline and manual diameter measurement via software caliper tools achieved an area under the receiver operating characteristic curve of 0.94 (95% CI, 0.83-0.99). CONCLUSIONS: We demonstrated that an LSTM network can be trained by using videos of IVC US to classify IVC collapse to predict fluid responsiveness. Our LSTM network performed moderately well given the small training cohort but worse than point-of-care US experts. Further training and testing of the LSTM network with a larger data sets is warranted.

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.

Racial And Ethnic Disparities In Care Following The New York State Sepsis Initiative.

After 2013, when New York State mandated that hospitals follow protocols to treat sepsis, completion of the protocols increased and mortality declined. Whether these encouraging trends have equitably benefited racial/ethnic minority populations is unknown. Although there were no significant racial/ethnic differences in rates of protocol completion at the onset of New York's Sepsis Initiative, over time white patients experienced a greater increase in protocol completion rates (14.0 percentage points) compared to black patients (5.3 percentage points). The emergence of this disparity was due to smaller performance improvements among hospitals with higher proportions of black patients, though white and black patients showed similar improvements when treated within the same hospital. Our study suggests an urgent need to understand why improvements in sepsis care lagged in hospitals in New York that care for higher proportions of minority patients. Policy makers should anticipate and monitor the effects of quality improvement initiatives on disparities to ensure that all racial/ethnic groups realize their benefits equitably.

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.

Bedside sonographic measurement of the inferior vena cava caval index is a poor predictor of fluid responsiveness in emergency department patients.

OBJECTIVES: Sonographic measurement of the inferior vena cava (IVC) caval index predicts central venous pressure in ED patients. Fluid responsiveness (FR) is a measure of preload dependence defined as an increase in cardiac output secondary to volume expansion. We sought to determine if the caval index is an accurate measurement of FR in ED patients. METHODS: We conducted a prospective, observational trial at an urban, academic, adult ED with an annual census >105 000. Included patients were clinically suspected of eu- and hypovolemia. Excluded patients were <18 years old, pregnant, incarcerated, sustained significant trauma or unable to consent. Supine IVC diameter was measured by bedside ultrasonography (M-Turbo; Sonosite, Bothwell, WA, USA). Caval index = [(expiratory IVC diameter - inspiratory IVC diameter)/expiratory IVC diameter] × 100. FR was defined as an increase in the cardiac index by >10% by impedance cardiography (BioZ; Sonosite) following passive leg raise. The primary outcome was analysed using Spearman correlations for non-parametric data and the area under the receiver operating characteristics curve by Wilcoxon method. RESULTS: Thirty patients were enrolled; four were excluded because of incomplete data collection. Thirty-one per cent (95% CI 13-48) of the patients were FR. The mean initial caval and cardiac index were 15.8% (95% CI 9.5-22) and 2.9 L/min/m(2) (95% CI 2.6-3.2), respectively. Caval index did not predict FR (receiver operating curve = 0.46, 95% CI 0.21-0.71, P = 0.63). CONCLUSION: Bedside sonographic measurement of IVC caval index does not predict FR in a heterogeneous ED patient population. Further research using this technique in targeted patient subsets and a variety of shock etiologies is needed.

Interrater reliability and parallel forms reliability of two noninvasive hemodynamic monitoring devices in clinically stable emergency department patients.

OBJECTIVE: To evaluate the interrater reliability and parallel forms reliability of transcutaneous Doppler ultrasonography (TCDU) and impedance cardiography (ICG) in clinically and hemodynamically stable emergency department patients. METHODS: We enrolled 30 emergency department patients over a 2-day period. Patients had three consecutive simultaneously blinded measurements of stroke volume (SV) and heart rate (HR) recorded by TCDU (USCOM) and ICG (Cardiodynamics). Two physicians, with basic familiarity but no clinical experience with either device recorded three measurements of SV and HR on each device. Intraclass correlation coefficients (ICC), mixed linear models for repeated measures, and Bland-Altman plots were used to assess interrater reliability and nature of relationships between measures from the devices (parallel forms reliability). RESULTS: The ICC for TCDU was 0.96 for HR and 0.95 for SV, whereas the ICC for ICG was 0.93 for HR and 0.98 for SV. The device HR estimates were significantly related (P<0.0001 for all slopes) for all phases, but SV failed to reach significance following the first 50 trials [t(94.2)=2.72, P=0.0077]. Although HR estimates were within reasonable clinical tolerances (bias 0.5%, limits of agreement -15.4 to 16.4%) SV disagreement was concerning (bias 3.8%, limits of agreement -58 to 66%). CONCLUSION: Both TCDU and ICG have fair interrater reliability of SV independent of operator experience. A statistically significant relationship exists between the two devices but this does not produce predictable values in SV. Over time comparative results become less biased but remain limited by a great degree of variability.

Prognostic value of noninvasive measures of contractility in emergency department patients with severe sepsis and septic shock undergoing early goal-directed therapy.

PURPOSE: Reversible ventricular dysfunction is common in sepsis. Impedance cardiography allows for noninvasive measurement of contractility through time interval or amplitude-based measures. This study evaluates the prognostic capacity of these measures in patients with severe sepsis or septic shock in the emergency department. METHODS: This is a prospective observational cohort study of 56 patients older than 18 years meeting criteria for early goal-directed therapy (lactate level >4 mmol/L or systolic blood pressure <90 mm Hg after 2-L isotonic sodium chloride solution). Continuous collections of contractility measures were performed, and patients were followed until discharge or in-hospital death. RESULTS: A significant 57% reduction in the accelerated contractility index (ACI) in nonsurvivors (71 1/s(2) [41-102]) compared with survivors (123 1/s(2) [98-147]) existed. Only ACI predicted in-hospital mortality (area under the receiver operating characteristic curve = 0.70, P < .01). Accelerated contractility index did not correlate with amount of prior fluid administration, central venous pressure, number of cardiac risk factors, or troponin I value. An ACI of less than 40 1/s(2) is 95% (84-99) specific with a positive likelihood ratio of 8.8 for predicting in-hospital mortality. CONCLUSIONS: A reduced ACI is associated with mortality in critically ill emergency department patients presenting with severe sepsis and septic shock meeting criteria for early goal-directed therapy. This association appears to be independent of clinical or laboratory predictors of cardiac dysfunction or preload.

Tissue oxygenation does not predict central venous oxygenation in emergency department patients with severe sepsis and septic shock.

OBJECTIVES: This study sought to determine whether tissue oxygenation (StO(2)) could be used as a surrogate for central venous oxygenation (ScVO(2)) in early goal-directed therapy (EGDT). METHODS: The study enrolled a prospective convenience sample of patients aged > or =18 years with sepsis and systolic blood pressure <90 mm Hg after 2 L of normal saline or lactate >4 mmol, who received a continuous central venous oximetry catheter. StO(2) and ScVO(2) were measured at 15-minute intervals. Data were analyzed using a random coefficients model, correlations, and Bland-Altman plots. RESULTS: There were 284 measurements in 40 patients. While a statistically significant relationship existed between StO(2) and ScVO(2) (F(1,37) = 10.23, p = 0.002), StO(2) appears to systematically overestimate at lower ScVO(2) and underestimate at higher ScVO(2). This was reflected in the fixed effect slope of 0.49 (95% confidence interval [CI] = 0.266 to 0.720) and intercept of 34 (95% CI = 14.681 to 50.830), which were significantly different from 1 and 0, respectively. The initial point correlation (r = 0.5) was fair, but there was poor overall agreement (bias = 4.3, limits of agreement = -20.8 to 29.4). CONCLUSIONS: Correlation between StO(2) and ScVO(2) was fair. The two measures trend in the same direction, but clinical use of StO(2) in lieu of ScVO(2) is unsubstantiated due to large and systematic biases. However, these biases may reflect real physiologic states. Further research may investigate if these measures could be used in concert as prognostic indicators.

The use of impedance cardiography in predicting mortality in emergency department patients with severe sepsis and septic shock.

OBJECTIVES: Pulmonary artery catheterization poses significant risks and requires specialized training. Technological advances allow for more readily available, noninvasive clinical measurements of hemodynamics. Few studies exist that assess the efficacy of noninvasive hemodynamic monitoring in sepsis patients. The authors hypothesized that cardiac index, as measured noninvasively by impedance cardiography (ICG) in emergency department (ED) patients undergoing early goal-directed therapy (EGDT) for sepsis, would be associated with in-hospital mortality. METHODS: This was a prospective observational cohort study of patients age over 18 years meeting criteria for EGDT (lactate > 4 or systolic blood pressure < 90 after 2 L of normal saline). Initial measurements of cardiac index were obtained by ICG. Patients were followed throughout their hospital course until discharge or in-hospital death. Cardiac index measures in survivors and nonsurvivors are presented as means and 95% confidence intervals (CI). Diagnostic performance of ICG in predicting mortality was tested by receiver operating characteristic (ROC) curve and areas under the ROC curves (AUC) were compared using Wilcoxon test. RESULTS: Fifty-six patients were enrolled; one was excluded due to an inability to complete data acquisition. The mean cardiac index in nonsurvivors (2.3 L/min.m(2), 95% CI = 1.6 to 3.0) was less than that for survivors (3.2, 95% CI = 2.9 to 3.5) with mean difference of 0.9 (95% CI = 0.12 to 1.71). The AUC for ICG in predicting mortality was 0.71 (95% CI = 0.58 to 0.88; p = 0.004). A cardiac index of < 2 L/min.m(2) had a sensitivity of 43% (95% CI = 18% to 71%), specificity of 93% (95% CI = 80% to 95%), positive likelihood ratio of 5.9, and negative likelihood ratio of 0.6 for predicting in-hospital mortality. CONCLUSIONS: Early, noninvasive measurement of the cardiac index in critically ill severe sepsis and septic shock patients can be performed in the ED for those who meet criteria for EGDT. There appears to be an association between an initial lower cardiac index as measured noninvasively and in-hospital mortality.