Fluid Therapy

ImportanceManeuvers assessing fluid responsiveness before an intravascular volume expansion may limit useless fluid administration, which in turn may improve outcomes.ObjectiveTo describe maneuvers for assessing fluid responsiveness in mechanically ventilated patients.RegistrationThe protocol was registered at PROSPERO: CRD42019146781.Information sources and searchPubMed, EMBASE, CINAHL, SCOPUS, and Web of Science were search from inception to 08/08/2023.Study selection and data collectionProspective and intervention studies were selected.Statistical analysisData for each maneuver were reported individually and data from the five most employed maneuvers were aggregated. A traditional and a Bayesian meta-analysis approach were performed.ResultsA total of 69 studies, encompassing 3185 fluid challenges and 2711 patients were analyzed. The prevalence of fluid responsiveness was 49.9%. Pulse pressure variation (PPV) was studied in 40 studies, mean threshold with 95% confidence intervals (95% CI) = 11.5 (10.5-12.4)%, and area under the receiver operating characteristics curve (AUC) with 95% CI was 0.87 (0.84-0.90). Stroke volume variation (SVV) was studied in 24 studies, mean threshold with 95% CI = 12.1 (10.9-13.3)%, and AUC with 95% CI was 0.87 (0.84-0.91). The plethysmographic variability index (PVI) was studied in 17 studies, mean threshold = 13.8 (12.3-15.3)%, and AUC was 0.88 (0.82-0.94). Central venous pressure (CVP) was studied in 12 studies, mean threshold with 95% CI = 9.0 (7.7-10.1) mmHg, and AUC with 95% CI was 0.77 (0.69-0.87). Inferior vena cava variation (∆IVC) was studied in 8 studies, mean threshold = 15.4 (13.3-17.6)%, and AUC with 95% CI was 0.83 (0.78-0.89).ConclusionsFluid responsiveness can be reliably assessed in adult patients under mechanical ventilation. Among the five maneuvers compared in predicting fluid responsiveness, PPV, SVV, and PVI were superior to CVP and ∆IVC. However, there is no data supporting any of the above mentioned as being the best maneuver. Additionally, other well-established tests, such as the passive leg raising test, end-expiratory occlusion test, and tidal volume challenge, are also reliable.

BackgroundIV fluids are recommended for adults with sepsis. However, the optimal strategy for IV fluid management in sepsis is unknown, and clinical equipoise exists.Research questionDo lower vs higher fluid volumes improve patient-important outcomes in adult patients with sepsis?Study design and methodsWe updated a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials assessing lower vs higher IV fluid volumes in adult patients with sepsis. The coprimary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. We followed the recommendations from the Cochrane Handbook and used the Grading of Recommendations Assessment, Development and Evaluation approach. Primary conclusions were based on trials with low risk of bias if available.ResultsWe included 13 trials (N = 4,006) with four trials (n = 3,385) added to this update. The meta-analysis of all-cause mortality in eight trials with low risk of bias showed a relative risk of 0.99 (97% CI, 0.89-1.10; moderate certainty evidence). Six trials with predefined definitions of serious adverse events showed a relative risk of 0.95 (97% CI, 0.83-1.07; low certainty evidence). Health-related quality of life was not reported.InterpretationAmong adult patients with sepsis, lower IV fluid volumes probably result in little to no difference in all-cause mortality compared with higher IV fluid volumes, but the interpretation is limited by imprecision in the estimate, which does not exclude potential benefit or harm. Similarly, the evidence suggests lower IV fluid volumes result in little to no difference in serious adverse events. No trials reported on health-related quality of life.Trial registrationPROSPERO; No.: CRD42022312572; URL: https://www.crd.york.ac.uk/prospero/.

BackgroundIn patients on mechanical ventilation, positive end-expiratory pressure (PEEP) can decrease cardiac output through a decrease in cardiac preload and/or an increase in right ventricular afterload. Increase in central blood volume by fluid administration or passive leg raising (PLR) may reverse these phenomena through an increase in cardiac preload and/or a reopening of closed lung microvessels. We hypothesized that a transient decrease in PEEP (PEEP-test) may be used as a test to detect volume responsiveness.MethodsMechanically ventilated patients with PEEP ≥ 10 cmH2O ("high level") and without spontaneous breathing were prospectively included. Volume responsiveness was assessed by a positive PLR-test, defined as an increase in pulse-contour-derived cardiac index (CI) during PLR ≥ 10%. The PEEP-test consisted in reducing PEEP from the high level to 5 cmH2O for one minute. Pulse-contour-derived CI (PiCCO2) was monitored during PLR and the PEEP-test.ResultsWe enrolled 64 patients among whom 31 were volume responsive. The median increase in CI during PLR was 14% (11-16%). The median PEEP at baseline was 12 (10-15) cmH2O and the PEEP-test resulted in a median decrease in PEEP of 7 (5-10) cmH2O, without difference between volume responsive and unresponsive patients. Among volume responsive patients, the PEEP-test induced a significant increase in CI of 16% (12-20%) (from 2.4 ± 0.7 to 2.9 ± 0.9 L/min/m2, p 8.6% during the PEEP-test with a sensitivity of 96.8% (95% confidence interval (95%CI): 83.3-99.9%) and a specificity of 84.9% (95%CI 68.1-94.9%). The area under the receiver operating characteristic curve of the PEEP-test for detecting volume responsiveness was 0.94 (95%CI 0.85-0.98) (p ConclusionsA CI increase > 8.6% during a PEEP-test, which consists in reducing PEEP to 5 cmH2O, reliably detects volume responsiveness in mechanically ventilated patients with a PEEP ≥ 10 cmH2O. Trial registration ClinicalTrial.gov (NCT 04,023,786). Registered July 18, 2019. Ethics Committee approval CPP Est III (N° 2018-A01599-46).

ImportanceAlbumin supplementation may reduce mortality in patients with septic shock; however, data from randomized clinical trials are limited.ObjectiveTo assess the impact of albumin administration on outcomes in patients with septic shock.Design, setting, and participantsThis multicenter, open-label randomized clinical trial was conducted between October 21, 2019, and May 2, 2022. Patients from 23 intensive care units in Germany enrolled within 24 hours of the onset of septic shock were followed up for outcome data up to 90 days. The statistical trial report was completed and filed with the federal authorities in December 2023; additional analyses were completed in October 2024. The study was terminated prematurely due to low enrollment rates.InterventionsProtocol group patients received 20% albumin to maintain serum albumin levels of at least 3.0 g/dL for up to 28 days during their intensive care unit admission. The control group received standard fluid administration with crystalloids.Main outcomes and measuresThe primary end point was 90-day mortality; secondary end points included 28-day, 60-day, intensive care unit and in-hospital mortality, organ dysfunction or failure, total amount of fluid administration and total fluid balance while in the intensive care unit, duration of intensive care and hospital stays, and frequency of adverse events.ResultsOf 440 randomized patients (median [IQR] age, 69 [59-78] years; 290 [65.9%] male), 222 received albumin and 218 received standard fluids. Baseline characteristics were comparable. Ninety-day mortality was 43.3% (91 of 210) in the albumin group vs 45.9% (96 of 209) in controls (relative risk, 0.94; 95% CI, 0.76-1.17; P = .71). No significant differences were observed for secondary end points.Conclusions and relevanceIn this randomized clinical trial of patients with septic shock, albumin administration was safe but did not improve 90-day survival. As this trial was prematurely terminated, results remain inconclusive and additional studies are recommended.Trial registrationClinicalTrials.gov Identifier: NCT03869385.