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Early Fluid Resuscitation and High Volume Hemofiltration Decrease Septic Shock Progression in Swine.

ABSTRACT: This study aimed to assess the effects of early fluid resuscitation (EFR) combined with high volume hemofiltration (HVHF) on the cardiopulmonary function and removal of inflammatory mediators in a septic shock swine model. Eighteen swine were randomized into three groups: control (n = 6) (extracorporeal circulating blood only), continuous renal replacement therapy (CRRT) (n = 6; ultrafiltration volume = 25 mL/Kg/h), and HVHF (n = 6; ultrafiltration volume = 85 mL/Kg/h). The septic shock model was established by intravenous infusion of lipopolysaccharides (50 µg/kg/h). Hemodynamic parameters (arterial pressure, heart rate, cardiac output, stroke volume variability, left ventricular contractility, systemic vascular resistance, and central venous pressure), vasoactive drug parameters (dose and time of norepinephrine and hourly fluid intake), pulmonary function (partial oxygen pressure and vascular permeability), and cytokines (interleukin-6 and interleukin-10) were observed. Treatment resulted in significant changes at 4-6 h. HVHF was beneficial, as shown by the dose of vasoactive drugs, fluid intake volume, left ventricular contractility index, and partial oxygen pressure. Both CRRT and HVHF groups showed improved removal of inflammatory mediators compared with controls. In conclusion, EFR combined with HVHF improved septic shock in this swine model. The combination decreased shock progression, reduced the need for vasoactive drugs, and alleviated the damage to cardiopulmonary functions.

SUBMITTER: Zhao P

PROVIDER: S-EPMC4620416 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Early Fluid Resuscitation and High Volume Hemofiltration Decrease Septic Shock Progression in Swine.

Zhao Ping P Zheng Ruiqiang R Xue Lu L Zhang Min M Wu Xiaoyan X

BioMed research international 20151012

This study aimed to assess the effects of early fluid resuscitation (EFR) combined with high volume hemofiltration (HVHF) on the cardiopulmonary function and removal of inflammatory mediators in a septic shock swine model. Eighteen swine were randomized into three groups: control (n = 6) (extracorporeal circulating blood only), continuous renal replacement therapy (CRRT) (n = 6; ultrafiltration volume = 25 mL/Kg/h), and HVHF (n = 6; ultrafiltration volume = 85 mL/Kg/h). The septic shock model wa ...[more]

PMID: 26543849

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Project description:BACKGROUND:Fluid boluses are administered to septic shock patients with the purpose of increasing cardiac output as a means to restore tissue perfusion. Unfortunately, fluid therapy has a narrow therapeutic index, and therefore, several approaches to increase safety have been proposed. Fluid responsiveness (FR) assessment might predict which patients will effectively increase cardiac output after a fluid bolus (FR+), thus preventing potentially harmful fluid administration in non-fluid responsive (FR-) patients. However, there are scarce data on the impact of assessing FR on major outcomes. The recent ANDROMEDA-SHOCK trial included systematic per-protocol assessment of FR. We performed a post hoc analysis of the study dataset with the aim of exploring the relationship between FR status at baseline, attainment of specific targets, and clinically relevant outcomes. METHODS:ANDROMEDA-SHOCK compared the effect of peripheral perfusion- vs. lactate-targeted resuscitation on 28-day mortality. FR was assessed before each fluid bolus and periodically thereafter. FR+ and FR- subgroups, independent of the original randomization, were compared for fluid administration, achievement of resuscitation targets, vasoactive agents use, and major outcomes such as organ dysfunction and support, length of stay, and 28-day mortality. RESULTS:FR could be determined in 348 patients at baseline. Two hundred and forty-two patients (70%) were categorized as fluid responders. Both groups achieved comparable successful resuscitation targets, although non-fluid responders received less resuscitation fluids (0 [0-500] vs. 1500 [1000-2500] mL; p 0.0001), exhibited less positive fluid balances, but received more vasopressor testing. No difference in clinically relevant outcomes between FR+ and FR- patients was found, including 24-h SOFA score (9 [5-12] vs. 8 [5-11], p = 0.4), need for MV (78% vs. 72%, p = 0.16), need for RRT (18% vs. 21%, p = 0.7), ICU-LOS (6 [3-11] vs. 6 [3-16] days, p = 0.2), and 28-day mortality (40% vs. 36%, p = 0.5). Only thirteen patients remained fluid responsive along the intervention period. CONCLUSIONS:Systematic assessment allowed determination of fluid responsiveness status in more than 80% of patients with early septic shock. Fluid boluses could be stopped in non-fluid responsive patients without any negative impact on clinical relevant outcomes. Our results suggest that fluid resuscitation might be safely guided by FR assessment in septic shock patients. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT03078712. Registered retrospectively on March 13, 2017.

Project description:IntroductionRecent evidence suggests that early, aggressive resuscitation in patients with septic shock reduces mortality. The objective of this survey was to characterize reported resuscitation practices of Canadian physicians caring for adult critically ill patients with early septic shock.MethodsA scenario-based self-administered national survey was sent out to Canadian critical care physicians. One hypothetical scenario was developed to obtain information on several aspects of resuscitation in early septic shock, including monitoring and resuscitation end-points, fluid administration, red blood cell transfusion triggers, and use of inotropes. The sampling frame was physician members of Canadian national and provincial critical care societies.ResultsThe survey response rate was 232 out of 355 (65.3%). Medicine was the most common primary specialty (60.0%), most respondents had practiced for 6 to 10 years (30.0%), and 82.0% were male. The following monitoring devices/parameters were reported as used/measured 'often' or 'always' by at least 89% of respondents: oxygen saturation (100%), Foley catheters (100%), arterial blood pressure lines (96.6%), telemetry (94.3%), and central venous pressure (89.2%). Continuous monitoring of central venous oxygen saturation was employed 'often' or 'always' by 9.8% of respondents. The two most commonly cited resuscitation end-points were urine output (96.5%) and blood pressure (91.8%). Over half of respondents used normal saline (84.5%), Ringers lactate (52.2%), and pentastarch (51.3%) 'often' or 'always' for early fluid resuscitation. In contrast, 5% and 25% albumin solutions were cited as used 'often' or 'always' by 3.9% and 1.3% of respondents, respectively. Compared with internists, surgeons and anesthesiologists (odds ratio (95% confidence interval): 9.8 (2.9 to 32.7) and 3.8 (1.7 to 8.7), respectively) reported greater use of Ringers lactate. In the setting of a low central venous oxygen saturation, 52.5% of respondents reported use of inotropic support 'often' or 'always'. Only 7.6% of physicians stated they would use a red blood cell transfusion trigger of 100 g/l to optimize oxygen delivery further.ConclusionOur survey results suggest that there is substantial practice variation in the resuscitation of adult patients with early septic shock. More randomized trials are needed to determine the optimal approach.

Project description:ObjectivesEvidence to guide fluid resuscitation evidence in sepsis continues to evolve. We conducted a multicountry survey of emergency and critical care physicians to describe current stated practice and practice variation related to the quantity, rapidity and type of resuscitation fluid administered in early septic shock to inform the design of future septic shock fluid resuscitation trials.MethodsUsing a web-based survey tool, we invited critical care and emergency physicians in Canada, the UK, Scandinavia and Saudi Arabia to complete a self-administered electronic survey.ResultsA total of 1097 physicians' responses were included. 1 L was the most frequent quantity of resuscitation fluid physicians indicated they would administer at a time (46.9%, n=499). Most (63.0%, n=671) stated that they would administer the fluid challenges as quickly as possible. Overall, normal saline and Ringer's solutions were the preferred crystalloid fluids used 'often' or 'always' in 53.1% (n=556) and 60.5% (n=632) of instances, respectively. However, emergency physicians indicated that they would use normal saline 'often' or 'always' in 83.9% (n=376) of instances, while critical care physicians said that they would use saline 'often' or 'always' in 27.9% (n=150) of instances. Only 1.0% (n=10) of respondents indicated that they would use hydroxyethyl starch 'often' or 'always'; use of 5% (5.6% (n=59)) or 20-25% albumin (1.3% (n=14)) was also infrequent. The majority (88.4%, n=896) of respondents indicated that a large randomised controlled trial comparing 5% albumin to a crystalloid fluid in early septic shock was important to conduct.ConclusionsCritical care and emergency physicians stated that they rapidly infuse volumes of 500-1000 mL of resuscitation fluid in early septic shock. Colloid use, specifically the use of albumin, was infrequently reported. Our survey identifies the need to conduct a trial on the efficacy of albumin and crystalloids on 90-day mortality in patients with early septic shock.

Project description:ObjectivesRapid fluid resuscitation has become standard in sepsis care, despite "low-quality" evidence and absence of guidelines for populations "at risk" for volume overload. Our objectives include as follows: 1) identify predictors of reaching a 30 mL/kg crystalloid bolus within 3 hours of sepsis onset (30by3); 2) assess the impact of 30by3 and fluid dosing on clinical outcomes; 3) examine differences in perceived "at-risk" volume-sensitive populations, including end-stage renal disease, heart failure, obesity, advanced age, or with documentation of volume "overload" by bedside examination.DesignRetrospective cohort study. All outcome analyses controlled for sex, end-stage renal disease, heart failure, sepsis severity (severe sepsis vs septic shock), obesity, Mortality in Emergency Department Sepsis score, and time to antibiotics.SettingUrban, tertiary care center between January 1, 2014, and May 31, 2017.PatientsEmergency Department treated adults (age ≥18 yr; n = 1,032) with severe sepsis or septic shock.InterventionsAdministration of IV fluids by bolus.Measurements and main resultsIn total, 509 patients received 30by3 (49.3%). Overall mortality was 17.1% (n = 176), with 20.4% mortality in the shock group. Patients who were elderly (odds ratio, 0.62; 95% CI, 0.46-0.83), male (odds ratio, 0.66; CI, 0.49-0.87), obese (odds ratio, 0.18; CI, 0.13-0.25), or with end-stage renal disease (odds ratio, 0.23; CI, 0.13-0.40), heart failure (odds ratio, 0.42; CI, 0.29-0.60), or documented volume "overload" (odds ratio, 0.30; CI, 0.20-0.45) were less likely to achieve 30by3. Failure to meet 30by3 had increased odds of mortality (odds ratio, 1.52; CI, 1.03-2.24), delayed hypotension (odds ratio, 1.42; CI, 1.02-1.99), and increased ICU stay (~2 d) (β = 2.0; CI, 0.5-3.6), without differential effects for "at-risk" groups. Higher fluid volumes administered by 3 hours correlated with decreased mortality, with a plateau effect between 35 and 45 mL/kg (p < 0.05).ConclusionsFailure to reach 30by3 was associated with increased odds of in-hospital mortality, irrespective of comorbidities. Predictors of inadequate resuscitation can be identified, potentially leading to interventions to improve survival. These findings are retrospective and require future validation.

Project description:IntroductionVenous-to-arterial carbon dioxide difference (Pv-aCO2) may reflect the adequacy of blood flow during shock states. We sought to test whether the development of Pv-aCO2 during the very early phases of resuscitation is related to multi-organ dysfunction and outcomes in a population of septic shock patients resuscitated targeting the usual oxygen-derived and hemodynamic parameters.MethodsWe conducted a prospective observational study in a 60-bed mixed ICU in a University affiliated Hospital. 85 patients with a new septic shock episode were included. A Pv-aCO2 value ? 6 mmHg was considered to be high. Patients were classified in four predefined groups according to the Pv-aCO2 evolution during the first 6 hours of resuscitation: (1) persistently high Pv-aCO2 (high at T0 and T6); (2) increasing Pv-aCO2 (normal at T0, high at T6); (3) decreasing Pv-aCO2 (high at T0, normal at T6); and (4) persistently normal Pv-aCO2 (normal at T0 and T6). Multiorgan dysfunction at day-3 was compared for predefined groups and a Kaplan Meier curve was constructed to show the survival probabilities at day-28 using a log-rank test to evaluate differences between groups. A Spearman-Rho was used to test the agreement between cardiac output and Pv-aCO2. Finally, we calculated the mortality risk ratios at day-28 among patients attaining normal oxygen parameters but with a concomitantly increased Pv-aCO2.ResultsPatients with persistently high and increasing Pv-aCO2 at T6 had significant higher SOFA scores at day-3 (p < 0.001) and higher mortality rates at day-28 (log rank test: 19.21, p < 0.001) compared with patients who evolved with normal Pv-aCO2 at T6. Interestingly, a poor agreement between cardiac output and Pv-aCO2 was observed (r2 = 0.025, p < 0.01) at different points of resuscitation. Patients who reached a central venous saturation (ScvO)2 ? 70% or mixed venous oxygen saturation (SvO2) ? 65% but with concomitantly high Pv-aCO2 at different developmental points (i.e., T0, T6 and T12) had a significant mortality risk ratio at day-28.ConclusionThe persistence of high Pv-aCO2 during the early resuscitation of septic shock was associated with more severe multi-organ dysfunction and worse outcomes at day-28. Although mechanisms conducting to increase Pv-aCO2 during septic shock are insufficiently understood, Pv-aCO2 could identify a high risk of death in apparently resuscitated patients.

Project description:BackgroundWe hypothesized that the cardiovascular responses to Surviving Sepsis Guidelines (SSG)-defined resuscitation are predictable based on the cardiovascular state.MethodsFifty-five septic patients treated by SSG were studied before and after volume expansion (VE), and if needed norepinephrine (NE) and dobutamine. We measured mean arterial pressure (MAP), cardiac index (CI), and right atrial pressure (Pra) and calculated pulse pressure and stroke volume variation (PPV and SVV), dynamic arterial elastance (Eadyn), arterial elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees), Ees/Ea (VAC), LV ejection efficiency (LVeff), mean systemic pressure analogue (Pmsa), venous return pressure gradient (Pvr), and cardiac performance (Eh), using standard formulae.ResultsAll patients were hypotensive (MAP 56.8 ± 3.1 mmHg) and tachycardic (113.1 ± 7.5 beat min-1), with increased lactate levels (lactate = 5.0 ± 4.2 mmol L-1) with a worsened VAC. CI was variable but > 2 L min-1 M-2 in 74%. Twenty-eight-day mortality was 48% and associated with admission lactate, blood urea nitrogen (BUN), and creatinine levels but not cardiovascular state. In all patients, both MAP and CI improved following VE, as well as cardiac contractility (Ees). Fluid administration improved Pra, Pmsa, and Pvr in all patients, whereas both HR and Ea decreased after VE, thus normalizing VAC. CI increases were proportional to baseline PPV and SVV. CI increases proportionally decreased PPV and SVV. VE increased MAP > 65 mmHg in 35/55 patients. MAP responders had higher PPV, SVV, and Eadyn than non-responders. NE was given to 20/55 patients in septic shock, but increased MAP > 65 mmHg in only 12. NE increased Ea, Eadyn, Pra, Pmsa, and VAC while decreasing HR, PPV, SVV, and LVeff. MAP responders had higher pre-NE Ees and lower VAC. Dobutamine was given to 6/8 patients who remained hypotensive following NE. It increased Ees, MAP, CI, and LVeff, while decreasing HR, Pra, and VAC. At all times and all steps of the protocol, CI changes were proportional to Pvr changes independent of treatment.ConclusionsThe cardiovascular response to SSG-based resuscitation is highly heterogeneous but predictable from pre-treatment measures of cardiovascular state.

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Early Fluid Resuscitation and High Volume Hemofiltration Decrease Septic Shock Progression in Swine.

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Early Fluid Resuscitation and High Volume Hemofiltration Decrease Septic Shock Progression in Swine.

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