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Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial.

ABSTRACT: BACKGROUND:Persistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. Therefore, pursuing lactate normalization may lead to the risk of fluid overload. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. We designed the present randomized controlled trial to address the impact of a CRT-targeted (CRT-T) vs. a lactate-targeted (LAC-T) fluid resuscitation strategy on fluid balances within 24 h of septic shock diagnosis. In addition, we compared the effects of both strategies on organ dysfunction, regional and microcirculatory flow, and tissue hypoxia surrogates. RESULTS:Forty-two fluid-responsive septic shock patients were randomized into CRT-T or LAC-T groups. Fluids were administered until target achievement during the 6 h intervention period, or until safety criteria were met. CRT-T was aimed at CRT normalization (??3 s), whereas in LAC-T the goal was lactate normalization (??2 mmol/L) or a 20% decrease every 2 h. Multimodal perfusion monitoring included sublingual microcirculatory assessment; plasma-disappearance rate of indocyanine green; muscle oxygen saturation; central venous-arterial pCO2 gradient/ arterial-venous O2 content difference ratio; and lactate/pyruvate ratio. There was no difference between CRT-T vs. LAC-T in 6 h-fluid boluses (875 [375-2625] vs. 1500 [1000-2000], p?=?0.3), or balances (982[249-2833] vs. 15,800 [740-6587, p?=?0.2]). CRT-T was associated with a higher achievement of the predefined perfusion target (62 vs. 24, p?=?0.03). No significant differences in perfusion-related variables or hypoxia surrogates were observed. CONCLUSIONS:CRT-targeted fluid resuscitation was not superior to a lactate-targeted one on fluid administration or balances. However, it was associated with comparable effects on regional and microcirculatory flow parameters and hypoxia surrogates, and a faster achievement of the predefined resuscitation target. Our data suggest that stopping fluids in patients with CRT???3 s appears as safe in terms of tissue perfusion. Clinical Trials: ClinicalTrials.gov Identifier: NCT03762005 (Retrospectively registered on December 3rd 2018).

SUBMITTER: Castro R

PROVIDER: S-EPMC7606372 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial.

Castro Ricardo R Kattan Eduardo E Ferri Giorgio G Pairumani Ronald R Valenzuela Emilio Daniel ED Alegría Leyla L Oviedo Vanessa V Pavez Nicolás N Soto Dagoberto D Vera Magdalena M Santis César C Astudillo Brusela B Cid María Alicia MA Bravo Sebastian S Ospina-Tascón Gustavo G Bakker Jan J Hernández Glenn G

Annals of intensive care 20201102 1

<h4>Background</h4>Persistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. Therefore, pursuing lactate normalization may lead to the risk of fluid overload. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. We designed the present randomize ...[more]

PMID: 33140173

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Project description:BACKGROUND:Capillary refill time (CRT) may improve more rapidly than lactate in response to increments in systemic flow. Therefore, it can be assessed more frequently during septic shock (SS) resuscitation. Hyperlactatemia, in contrast, exhibits a slower recovery in SS survivors, probably explained by the delayed resolution of non-hypoperfusion-related sources. Thus, targeting lactate normalization may be associated with impaired outcomes. The ANDROMEDA-SHOCK trial compared CRT- versus lactate-targeted resuscitation in early SS. CRT-targeted resuscitation associated with lower mortality and organ dysfunction; mechanisms were not investigated. CRT was assessed every 30 min and lactate every 2 h during the 8-h intervention period, allowing a first comparison between groups at 2 h (T2). Our primary aim was to determine if SS patients evolving with normal CRT at T2 after randomization (T0) exhibited a higher mortality and organ dysfunction when allocated to the LT arm than when randomized to the CRT arm. Our secondary aim was to determine if those patients with normal CRT at T2 had received more therapeutic interventions when randomized to the LT arm. To address these issues, we performed a post hoc analysis of the ANDROMEDA-SHOCK dataset. RESULTS:Patients randomized to the lactate arm at T0, evolving with normal CRT at T2 exhibited significantly higher mortality than patients with normal CRT at T2 initially allocated to CRT (40 vs 23%, p?=?0.009). These results replicated at T8 and T24. LT arm received significantly more resuscitative interventions (fluid boluses: 1000[500-2000] vs. 500[0-1500], p?=?0.004; norepinephrine test in previously hypertensive patients: 43 (35) vs. 19 (19), p?=?0.001; and inodilators: 16 (13) vs. 3 (3), p?=?0.003). A multivariate logistic regression of patients with normal CRT at T2, including APACHE-II, baseline lactate, cumulative fluids administered since emergency admission, source of infection, and randomization group) confirmed that allocation to LT group was a statistically significant determinant of 28-day mortality (OR 3.3; 95%CI[1.5-7.1]); p?=?0.003). CONCLUSIONS:Septic shock patients with normal CRT at baseline received more therapeutic interventions and presented more organ dysfunction when allocated to the lactate group. This could associate with worse outcomes.

Project description:BackgroundRecent clinical studies have confirmed the strong prognostic value of persistent hyperlactatemia and delayed lactate clearance in septic shock. Several potential hypoxic and nonhypoxic mechanisms have been associated with persistent hyperlactatemia, but the relative contribution of these factors has not been specifically addressed in comprehensive clinical physiological studies. Our goal was to determine potential hemodynamic and perfusion-related parameters associated with 6-hour lactate clearance in a cohort of hyperdynamic, hyperlactatemic, septic shock patients.MethodsWe conducted an acute clinical physiological pilot study that included 15 hyperdynamic, septic shock patients undergoing aggressive early resuscitation. Several hemodynamic and perfusion-related parameters were measured immediately after preload optimization and 6 hours thereafter, with 6-hour lactate clearance as the main outcome criterion. Evaluated parameters included cardiac index, mixed venous oxygen saturation, capillary refill time and central-to-peripheral temperature difference, thenar tissue oxygen saturation (StO2) and its recovery slope after a vascular occlusion test, sublingual microcirculatory assessment, gastric tonometry (pCO2 gap), and plasma disappearance rate of indocyanine green (ICG-PDR). Statistical analysis included Wilcoxon and Mann-Whitney tests.ResultsFive patients presented a 6-hour lactate clearance <10%. Compared with 10 patients with a 6-hour lactate clearance ≥10%, they presented a worse hepatosplanchnic perfusion as represented by significantly more severe derangements of ICG-PDR (9.7 (8-19) vs. 19.6 (9-32)%/min, p < 0.05) and pCO2 gap (33 (9.1-62) vs. 7.7 (3-58) mmHg, p < 0.05) at 6 hours. No other systemic, hemodynamic, metabolic, peripheral, or microcirculatory parameters differentiated these subgroups. We also found a significant correlation between ICG-PDR and pCO2 gap (p = 0.02).ConclusionsImpaired 6-hour lactate clearance could be associated with hepatosplanchnic hypoperfusion in some hyperdynamic septic shock patients. Improvement of systemic, metabolic, and peripheral perfusion parameters does not rule out the persistence of hepatosplanchnic hypoperfusion in this setting. Severe microcirculatory abnormalities can be detected in hyperdynamic septic shock patients, but their role on lactate clearance is unclear. ICG-PDR may be a useful tool to evaluate hepatosplanchnic perfusion in septic shock patients with persistent hyperlactatemia.Trial registrationClinicalTrials.gov Identifier: NCT01271153.

Project description:BackgroundThe decision of when to stop septic shock resuscitation is a critical but yet a relatively unexplored aspect of care. This is especially relevant since the risks of over-resuscitation with fluid overload or inotropes have been highlighted in recent years. A recent guideline has proposed normalization of central venous oxygen saturation and/or lactate as therapeutic end-points, assuming that these variables are equivalent or interchangeable. However, since the physiological determinants of both are totally different, it is legitimate to challenge the rationale of this proposal. We designed this study to gain more insights into the most appropriate resuscitation goal from a dynamic point of view. Our objective was to compare the normalization rates of these and other potential perfusion-related targets in a cohort of septic shock survivors.MethodsWe designed a prospective, observational clinical study. One hundred and four septic shock patients with hyperlactatemia were included and followed until hospital discharge. The 84 hospital-survivors were kept for final analysis. A multimodal perfusion assessment was performed at baseline, 2, 6, and 24 h of ICU treatment.ResultsSome variables such as central venous oxygen saturation, central venous-arterial pCO2 gradient, and capillary refill time were already normal in more than 70% of survivors at 6 h. Lactate presented a much slower normalization rate decreasing significantly at 6 h compared to that of baseline (4.0 [3.0 to 4.9] vs. 2.7 [2.2 to 3.9] mmol/L; p?<?0.01) but with only 52% of patients achieving normality at 24 h. Sublingual microcirculatory variables exhibited the slowest recovery rate with persistent derangements still present in almost 80% of patients at 24 h.ConclusionsPerfusion-related variables exhibit very different normalization rates in septic shock survivors, most of them exhibiting a biphasic response with an initial rapid improvement, followed by a much slower trend thereafter. This fact should be taken into account to determine the most appropriate criteria to stop resuscitation opportunely and avoid the risk of over-resuscitation.

Project description:Background: Some septic shock patients have persistent hyperlactacidemia despite a normal systemic hemodynamics after resuscitation. Central venous oxygen saturation (ScvO2), mean arterial pressure (MAP), and central venous pressure (CVP) cannot be target in subsequent hemodynamic treatments. Vasoplegia is considered to be one of the main causes of oxygen metabolism abnormalities in septic shock patients, and norepinephrine (NE) is the first-line vasopressor in septic shock treatment; its dosage represents the severity of vasoplegia. This study was performed to determine whether vasoplegia, as assessed by NE dosage, can indicate patients' lactate clearance after the completion of resuscitation. Methods: A retrospective study was performed, and 106 patients with septic shock in an intensive care unit were analyzed. Laboratory values and hemodynamic variables were obtained upon completion of resuscitation (H 0) and 6 h after (H 6). Lactate clearance was defined as the percent decrease in lactate from H 0 to H 6. Student's t-test, Mann-Whitney U-test, Chi-square or Fisher's exact tests, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were performed for statistical analysis. Results: Patients with a mean age of 63.7 ± 13.8 years, baseline APACHE II score of 21.0 ± 5.1, and SOFA score of 12.7 ± 2.7 were enrolled. The study found that after 6-h of resuscitation, lactate clearance (LC) was <10% in 33 patients (31.1%). Patients with 6-h LC <10% compared with 6-h LC ≥ 10% had a higher NE dose (μg·kg-1·min-1) (0.55 [0.36-0.84] vs. 0.25 [0.18-0.41], p < 0.001). Multivariate logistic regression analysis of statistically significant univariate variables showed that NE dose had a significant inverse relationship with 6-h LC < 10%. The cutoff for NE was ≥ 0.32 μg·kg-1·min-1 for predicting 6-h lactate clearance after resuscitation, with a sensitivity of 75.76% and a specificity of 70.00%. Septic shock patients with an NE dose ≥ 0.32 μg·kg-1·min-1, relative to patients with an NE dose < 0.32 μg·kg-1·min-1, had a greater 30-day mortality rate (69.8% vs. 26.4% p < 0.001). Conclusion: Some patients with septic shock had persistent oxygen metabolism disorders after hemodynamic resuscitation. NE dose may indicate vasoplegia and oxygen metabolism disorder. After resuscitation, septic shock patients with high-dose NE have lower lactate clearance and a greater 30-day mortality rate than those with low-dose NE.

Project description:BackgroundAssessment of tissue hypoxia at the bedside has yet to be translated into daily clinical practice in septic shock patients. Perfusion markers are surrogates of deeper physiological phenomena. Lactate-to-pyruvate ratio (LPR) and the ratio between veno-arterial PCO2 difference and Ca-vO2 (ΔPCO2/Ca-vO2) have been proposed as markers of tissue hypoxia, but they have not been compared in the clinical scenario. We studied acute septic shock patients under resuscitation. We wanted to evaluate the relationship of these hypoxia markers with clinical and biochemical markers of hypoperfusion during septic shock resuscitation.MethodsSecondary analysis of a randomized controlled trial. Septic shock patients were randomized to fluid resuscitation directed to normalization of capillary refill time (CRT) versus normalization or significant lowering of lactate. Multimodal assessment of perfusion was performed at 0, 2, 6 and 24 hours, and included macrohemodynamic and metabolic perfusion variables, CRT, regional flow and hypoxia markers. Patients who attained their pre-specified endpoint at 2-hours were compared to those who did not.ResultsForty-two patients were recruited, median APACHE-II score was 23 [15-31] and 28-day mortality 23%. LPR and ΔPCO2/Ca-vO2 ratio did not correlate during early resuscitation (0-2 h) and the whole study period (24-hours). ΔPCO2/Ca-vO2 ratio derangements were more prevalent than LPR ones, either in the whole cohort (52% vs. 23%), and in association with other perfusion abnormalities. In patients who reached their resuscitation endpoints, the proportion of patients with altered ΔPCO2/Ca-vO2 ratio decreased significantly (66% to 33%, P=0.045), while LPR did not (14% vs. 25%, P=0.34).ConclusionsHypoxia markers did not exhibit correlation during resuscitation in septic shock patients. They probably interrogate different pathophysiological processes and mechanisms of dysoxia during early septic shock. Future studies should better elucidate the interaction and clinical role of hypoxia markers during septic shock resuscitation.

Project description:ImportanceAbnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established.ObjectiveTo determine if a peripheral perfusion-targeted resuscitation during early septic shock in adults is more effective than a lactate level-targeted resuscitation for reducing mortality.Design, setting, and participantsMulticenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018.InterventionsPatients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period.Main outcomes and measuresThe primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation-, renal replacement therapy-, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay.ResultsAmong 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, -8.5% [95% CI, -18.2% to 1.2%]). Peripheral perfusion-targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, -1.00 [95% CI, -1.97 to -0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed.Conclusions and relevanceAmong patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality.Trial registrationClinicalTrials.gov Identifier: NCT03078712.

Dataset Information

Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial.

Publications

Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial.

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