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Blood lactate is a marker of tissue hypoxia while capillary refill time (CRT) is a surrogate of tissue perfusion. Measuring these parameters is recommended for assessing circulatory status and guiding resuscitation. However, blood lactate is not widely available in African emergency departments. Additionally, CRT assessment faces challenges related to its precision and reproducibility. This study aims to evaluate the accuracy of visual CRT(V-CRT) compared to plethysmographic CRT (P-CRT) in predicting lactate levels among septic patients. This prospective observational study enrolled consecutive patients with sepsis or septic shock over a 6-month period from a tertiary hospital in Marrakech, Morroco. V-CRT and P-CRT were evaluated upon admission, and simultaneous measurements of arterial lactate levels were obtained. The precision of V-CRT and P-CRT in predicting arterial lactate was assessed using ROC curve analysis. Forty-three patients aged of 64±15 years, of whom 70 % were male, were included in the study. Of these, 23 patients (53 %) had sepsis, and 20 patients (47 %) experienced septic shock. Both V-CRT and P-CRT demonstrated statistically significant correlations with arterial lactate, with correlation coefficients of 0.529 (p < 0.0001) and 0.517 (p = 0.001), respectively. ROC curve analysis revealed that V-CRT exhibited satisfactory accuracy in predicting arterial lactate levels >2 mmol/l, with an area under the curve (AUC) of 0.8 (95 % CI=0.65 – 0.93; p < 0.0001). The prediction ability of P-CRT was lower than V-CRT with an AUC of 0.73 (95 % CI: 0.57–0.89; p = 0.043). The optimal thresholds were determined as 3.4 s for V-CRT (sensitivity = 90 %, specificity = 58 %) and 4.1 s for P-CRT (sensitivity = 85 %, specificity = 62 %). These findings suggest that the plethysmographic evaluation did not improve the accuracy of CRT for predicting lactate level. However, V-CRT may still serve as a viable surrogate for lactate in septic patients in low-income settings. [ABSTRACT FROM AUTHOR]

Introduction: Blood lactate is a marker of tissue hypoxia while capillary refill time (CRT) is a surrogate of tissue perfusion. Measuring these parameters is recommended for assessing circulatory status and guiding resuscitation. However, blood lactate is not widely available in African emergency departments. Additionally, CRT assessment faces challenges related to its precision and reproducibility. This study aims to evaluate the accuracy of visual CRT(V-CRT) compared to plethysmographic CRT (P-CRT) in predicting lactate levels among septic patients. Methods: This prospective observational study enrolled consecutive patients with sepsis or septic shock over a 6-month period from a tertiary hospital in Marrakech, Morroco. V-CRT and P-CRT were evaluated upon admission, and simultaneous measurements of arterial lactate levels were obtained. The precision of V-CRT and P-CRT in predicting arterial lactate was assessed using ROC curve analysis. Results: Forty-three patients aged of 64±15 years, of whom 70 % were male, were included in the study. Of these, 23 patients (53 %) had sepsis, and 20 patients (47 %) experienced septic shock. Both V-CRT and P-CRT demonstrated statistically significant correlations with arterial lactate, with correlation coefficients of 0.529 (p < 0.0001) and 0.517 (p = 0.001), respectively. ROC curve analysis revealed that V-CRT exhibited satisfactory accuracy in predicting arterial lactate levels >2 mmol/l, with an area under the curve (AUC) of 0.8 (95 % CI=0.65 – 0.93; p < 0.0001). The prediction ability of P-CRT was lower than V-CRT with an AUC of 0.73 (95 % CI: 0.57–0.89; p = 0.043). The optimal thresholds were determined as 3.4 s for V-CRT (sensitivity = 90 %, specificity = 58 %) and 4.1 s for P-CRT (sensitivity = 85 %, specificity = 62 %). Conclusion: These findings suggest that the plethysmographic evaluation did not improve the accuracy of CRT for predicting lactate level. However, V-CRT may still serve as a viable surrogate for lactate in septic patients in low-income settings.

Purpose: Capillary Refill Time (CRT) measurement has gained increasing attention in the field of sepsis and septic shock. Recognizing pressure as a fundamental determinant in CRT measurement is crucial for establishing a standardized CRT measurement procedure. In this preliminary study, we elucidated the optimal pressing strength for CRT measurement by analyzing the CRTs measured under varying pressures. Method: Seventeen healthy individuals were enlisted to undergo CRT tests on their fingertips at various pressure levels. The applied force was initiated at 0.5N and incrementally increased by 0.5N until it reached 10.5N. An integrated Photoplethysmography (PPG) device was employed to capture fluctuations in light intensity. The CRT was automatically derived from the PPG signals via a specialized algorithm. The study included correlation assessment and reliability evaluation. Box plot and Bland-Altman plot were used to visualize the impact of pressure levels on CRTs. Results: A dataset of 1414 CRTs across 21 pressures showed significant differences (Kruskal-Wallis test, p

Abstract Background Several studies have validated capillary refill time (CRT) as a marker of tissue hypoperfusion, and recent guidelines recommend CRT monitoring during septic shock resuscitation. Therefore, it is relevant to further explore its kinetics of response to short-term hemodynamic interventions with fluids or vasopressors. A couple of previous studies explored the impact of a fluid bolus on CRT, but little is known about the impact of norepinephrine on CRT when aiming at a higher mean arterial pressure (MAP) target in septic shock. We designed this observational study to further evaluate the effect of a fluid challenge (FC) and a vasopressor test (VPT) on CRT in septic shock patients with abnormal CRT after initial resuscitation. Our purpose was to determine the effects of a FC in fluid-responsive patients, and of a VPT aimed at a higher MAP target in chronically hypertensive fluid-unresponsive patients on the direction and magnitude of CRT response. Methods Thirty-four septic shock patients were included. Fluid responsiveness was assessed at baseline, and a FC (500 ml/30 mins) was administered in 9 fluid-responsive patients. A VPT was performed in 25 patients by increasing norepinephrine dose to reach a MAP to 80–85 mmHg for 30 min. Patients shared a multimodal perfusion and hemodynamic monitoring protocol with assessments at at least two time-points (baseline, and at the end of interventions). Results CRT decreased significantly with both tests (from 5 [3.5–7.6] to 4 [2.4–5.1] sec, p = 0.008 after the FC; and from 4.0 [3.3–5.6] to 3 [2.6 -5] sec, p = 0.03 after the VPT. A CRT-response was observed in 7/9 patients after the FC, and in 14/25 pts after the VPT, but CRT deteriorated in 4 patients on this latter group, all of them receiving a concomitant low-dose vasopressin. Conclusions Our findings support that fluid boluses may improve CRT or produce neutral effects in fluid-responsive septic shock patients with persistent hypoperfusion. Conversely, raising NE doses to target a higher MAP in previously hypertensive patients elicits a more heterogeneous response, improving CRT in the majority, but deteriorating skin perfusion in some patients, a fact that deserves further research.

Abstract Introduction This study aimed to compare the predictive abilities of macrocirculation markers (mean arterial pressure, heart rate, and central venous pressure), microcirculation markers (capillary refill time and peripheral perfusion index), as well as fluid balance, lactate level, and lactate clearance on the outcomes of patients with septic shock during initial resuscitation. Methods In this prospective, single-center observational study, adult patients with septic shock admitted to the intensive care unit (ICU) at Shohada Hospital in Tabriz, Iran, between December 2020 and September 2021, were included. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression were used to assess the associations between macrocirculation markers (heart rate, mean arterial pressure, central venous pressure, and fluid balance) and microcirculation markers (capillary refill time, peripheral perfusion index, mottling score, lactate level, and lactate clearance level) with outcomes such as ICU length of stay, need for renal replacement therapy (RRT), vasopressor requirements, duration of mechanical ventilation (MV), and mortality rate. Assessments were performed at baseline, 6 h, and 24 h after fluid resuscitation. Results A total of 100 patients with septic shock (55 men and 45 women) were enrolled in the study. The area under the curve (AUC) values for the macrocirculation and microcirculation markers in predicting mortality ranged from 0.517 to 0.770 and 0.695 to 0.993, respectively. Among the macrocirculation markers, central venous pressure and mean arterial pressure at baseline showed the best predictive values for mortality, with AUCs of 0.770 and 0.753, respectively. Conclusion In patients with septic shock, microcirculation markers, particularly the peripheral perfusion index (PPI), demonstrated better predictive accuracy for mortality compared to macrocirculation markers. Furthermore, the combination of markers had a higher AUC, sensitivity, and specificity for predicting outcomes compared to individual markers alone.

Abstract Background In this study, we aimed to evaluate the ability of central-to-peripheral temperature gradients using thermal imaging to predict in-hospital mortality in surgical patients with septic shock. Methods This prospective observational study included adult patients with septic shock admitted to the intensive care unit postoperatively. Serum lactate (in mmol/L), capillary refill time (CRT) (in seconds), toe (peripheral) and canthal (central) temperature by infrared thermography and the corresponding room temperature in (Celsius [°C]) were assessed at the time of admission, 6- and 12 h after admission. The canthal-toe and room-toe temperature gradients were calculated. According to their final outcomes, patients were divided into survivors and non-survivors. The ability of canthal-toe temperature gradient (primary outcome), room-toe temperature gradient, toe temperature, serum lactate and CRT, measured at the prespecified timepoints to predict in-hospital mortality was analyzed using the area under receiver operating characteristic curve (AUC). Results Fifty-six patients were included and were available for the final analysis and 41/56 (73%) patients died. The canthal-toe and room-toe temperature gradients did not show significant accuracy in predicting mortality at any timepoint. Only the toe temperature measurement at 12 h showed good ability in predicting in-hospital mortality with AUC (95% confidence interval) of 0.72 (0.58–0.84) and a negative predictive value of 70% at toe temperature of ≤ 25.5 °C. Both serum lactate and CRT showed good ability to predict in-hospital mortality at all timepoints with high positive predictive values (> 90%) at cut-off value of > 2.5–4.3 mmol/L for the serum lactate and > 3-4.2 s for the CRT. Conclusion In post-operative emergency surgical patients with septic shock, high serum lactate and CRT can accurately predict in-hospital mortality and were superior to thermal imaging, especially in the positive predictive values. Toe temperature > 25.5 °C, measured using infrared thermal imaging can exclude in-hospital mortality with a negative predictive value of 70%.

Background: Several studies have validated capillary refill time (CRT) as a marker of tissue hypoperfusion, and recent guidelines recommend CRT monitoring during septic shock resuscitation. Therefore, it is relevant to further explore its kinetics of response to short-term hemodynamic interventions with fluids or vasopressors. A couple of previous studies explored the impact of a fluid bolus on CRT, but little is known about the impact of norepinephrine on CRT when aiming at a higher mean arterial pressure (MAP) target in septic shock. We designed this observational study to further evaluate the effect of a fluid challenge (FC) and a vasopressor test (VPT) on CRT in septic shock patients with abnormal CRT after initial resuscitation. Our purpose was to determine the effects of a FC in fluid-responsive patients, and of a VPT aimed at a higher MAP target in chronically hypertensive fluid-unresponsive patients on the direction and magnitude of CRT response. Methods: Thirty-four septic shock patients were included. Fluid responsiveness was assessed at baseline, and a FC (500 ml/30 mins) was administered in 9 fluid-responsive patients. A VPT was performed in 25 patients by increasing norepinephrine dose to reach a MAP to 80–85 mmHg for 30 min. Patients shared a multimodal perfusion and hemodynamic monitoring protocol with assessments at at least two time-points (baseline, and at the end of interventions). Results: CRT decreased significantly with both tests (from 5 [3.5–7.6] to 4 [2.4–5.1] sec, p = 0.008 after the FC; and from 4.0 [3.3–5.6] to 3 [2.6 -5] sec, p = 0.03 after the VPT. A CRT-response was observed in 7/9 patients after the FC, and in 14/25 pts after the VPT, but CRT deteriorated in 4 patients on this latter group, all of them receiving a concomitant low-dose vasopressin. Conclusions: Our findings support that fluid boluses may improve CRT or produce neutral effects in fluid-responsive septic shock patients with persistent hypoperfusion. Conversely, raising NE doses to target a higher MAP in previously hypertensive patients elicits a more heterogeneous response, improving CRT in the majority, but deteriorating skin perfusion in some patients, a fact that deserves further research. [ABSTRACT FROM AUTHOR]

Background: In this study, we aimed to evaluate the ability of central-to-peripheral temperature gradients using thermal imaging to predict in-hospital mortality in surgical patients with septic shock. Methods: This prospective observational study included adult patients with septic shock admitted to the intensive care unit postoperatively. Serum lactate (in mmol/L), capillary refill time (CRT) (in seconds), toe (peripheral) and canthal (central) temperature by infrared thermography and the corresponding room temperature in (Celsius [°C]) were assessed at the time of admission, 6- and 12 h after admission. The canthal-toe and room-toe temperature gradients were calculated. According to their final outcomes, patients were divided into survivors and non-survivors. The ability of canthal-toe temperature gradient (primary outcome), room-toe temperature gradient, toe temperature, serum lactate and CRT, measured at the prespecified timepoints to predict in-hospital mortality was analyzed using the area under receiver operating characteristic curve (AUC). Results: Fifty-six patients were included and were available for the final analysis and 41/56 (73%) patients died. The canthal-toe and room-toe temperature gradients did not show significant accuracy in predicting mortality at any timepoint. Only the toe temperature measurement at 12 h showed good ability in predicting in-hospital mortality with AUC (95% confidence interval) of 0.72 (0.58–0.84) and a negative predictive value of 70% at toe temperature of ≤ 25.5 °C. Both serum lactate and CRT showed good ability to predict in-hospital mortality at all timepoints with high positive predictive values (> 90%) at cut-off value of > 2.5–4.3 mmol/L for the serum lactate and > 3-4.2 s for the CRT. Conclusion: In post-operative emergency surgical patients with septic shock, high serum lactate and CRT can accurately predict in-hospital mortality and were superior to thermal imaging, especially in the positive predictive values. Toe temperature > 25.5 °C, measured using infrared thermal imaging can exclude in-hospital mortality with a negative predictive value of 70%. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to compare the predictive abilities of macrocirculation markers (mean arterial pressure, heart rate, and central venous pressure), microcirculation markers (capillary refill time and peripheral perfusion index), as well as fluid balance, lactate level, and lactate clearance on the outcomes of patients with septic shock during initial resuscitation. Methods: In this prospective, single-center observational study, adult patients with septic shock admitted to the intensive care unit (ICU) at Shohada Hospital in Tabriz, Iran, between December 2020 and September 2021, were included. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression were used to assess the associations between macrocirculation markers (heart rate, mean arterial pressure, central venous pressure, and fluid balance) and microcirculation markers (capillary refill time, peripheral perfusion index, mottling score, lactate level, and lactate clearance level) with outcomes such as ICU length of stay, need for renal replacement therapy (RRT), vasopressor requirements, duration of mechanical ventilation (MV), and mortality rate. Assessments were performed at baseline, 6 h, and 24 h after fluid resuscitation. Results: A total of 100 patients with septic shock (55 men and 45 women) were enrolled in the study. The area under the curve (AUC) values for the macrocirculation and microcirculation markers in predicting mortality ranged from 0.517 to 0.770 and 0.695 to 0.993, respectively. Among the macrocirculation markers, central venous pressure and mean arterial pressure at baseline showed the best predictive values for mortality, with AUCs of 0.770 and 0.753, respectively. Conclusion: In patients with septic shock, microcirculation markers, particularly the peripheral perfusion index (PPI), demonstrated better predictive accuracy for mortality compared to macrocirculation markers. Furthermore, the combination of markers had a higher AUC, sensitivity, and specificity for predicting outcomes compared to individual markers alone. [ABSTRACT FROM AUTHOR]

Purpose: Acute circulatory failure leads to tissue hypoperfusion. Capillary refill time (CRT) has been widely studied, but its predictive value remains debated. We conducted a meta-analysis to assess the ability of CRT to predict death or adverse events in a context at risk or confirmed acute circulatory failure in adults. Method: MEDLINE, EMBASE, and Google scholar databases were screened for relevant studies. The pooled area under the ROC curve (AUC ROC), sensitivity, specificity, threshold, and diagnostic odds ratio using a random-effects model were determined. The primary analysis was the ability of abnormal CRT to predict death in patients with acute circulatory failure. Secondary analysis included the ability of CRT to predict death or adverse events in patients at risk or with confirmed acute circulatory failure, the comparison with lactate, and the identification of explanatory factors associated with better accuracy. Results: A total of 60,656 patients in 23 studies were included. Concerning the primary analysis, the pooled AUC ROC of 13 studies was 0.66 (95%CI [0.59; 0.76]), and pooled sensitivity was 54% (95%CI [43; 64]). The pooled specificity was 72% (95%CI [55; 84]). The pooled diagnostic odds ratio was 3.4 (95%CI [1.4; 8.3]). Concerning the secondary analysis, the pooled AUC ROC of 23 studies was 0.69 (95%CI [0.65; 0.74]). The prognostic value of CRT compared to lactate was not significantly different. High-quality CRT was associated with a greater accuracy. Conclusion: CRT poorly predicted death and adverse events in patients at risk or established acute circulatory failure. Its accuracy is greater when high-quality CRT measurement is performed. [ABSTRACT FROM AUTHOR]

Background: Skin mottling as a clinical perfusion marker in septic shock is significantly associated with severity and outcome in white-skinned population and its validity as a clinical sign in dark-skinned population is not known. The objectives of this study were to evaluate mottling in septic shock in the Indian ethnic population who has different skin color as compared to the white-skinned population and to assess mottling as an outcome predictor with capillary refill time (CRT) and other biochemical parameters which are the established clinical markers of perfusion in septic shock. Materials and methods: We conducted a prospective observational study of patients with skin color categories 21-34 on the von Luschan scale or Fitzprick type IV-VI who had septic shock needing a high dose of norepinephrine ≥0.2 µg/kg/min after fluid optimization. The study was conducted in a mixed medical-surgical ICU over 12 months. Two blinded experts (a Dermatologist and a plastic surgeon) independently classified the skin type, validated the occurrence of mottling, and scored mottling in our patients. We recorded the demographics, hemodynamic variables, and mottling score and observed the incidence of mottling and its correlation with predictors of the severity of septic shock. We also compared CRT, arterial lactate, central venous oxygen saturation, and venoarterial PCO2 gap with occurrence of mottling in septic shock patients. Results: We included 108 patients with age 61 ± 16 years. Mean Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores at enrolment were 10.3-21.9, respectively. Incidence of mottling was 20.3% (22/108). CRT >3 seconds was observed in 50.9% (55/108). Development of mottling was significantly associated with 90-day mortality; 20/22 (90.9%) patients died in the mottling group versus 58/86 (65.1%) in the non-mottling group (p = 0.028). Capillary refill time >3 seconds did not corelate with mortality; 40/55 (72.7%) Patients with CRT >3 seconds died versus 32/53 (60.4%) patients died in CRT ≤3 seconds group. Occurrence of mottling could predict mortality; positive predictive value of 90.9% which was comparable to positive predictive value of lactate levels >4 mmol/L, i.e., 94.1%. Conclusion: The incidence of mottling in septic shock is much less in patients of Indian ethnicity with brown skin color than in white-skinned population. Occurrence of mottling and not delayed CRT, is a better predictor of outcome in this setting. [ABSTRACT FROM AUTHOR]

Background: Capillary refill time (CRT) has been suggested as a variable to follow during the course of septic shock. We systematically investigated the effects on CRT of volume expansion and norepinephrine. Methods: In 69 septic shock patients, we recorded mean arterial pressure (MAP), cardiac index (CI), and 5 consecutive CRT measurements (video method, standardized pressure applied on the fingertip) before and after a 500-mL saline infusion in 33 patients and before and after an increase of the norepinephrine dose in 36 different patients. Fluid responders were defined by an increase in CI ≥ 15%, and norepinephrine responders by an increase in MAP ≥ 15%. Results: The least significant change of CRT was 23%, so that changes in CRT were considered significant if larger than 23%. With volume expansion, CRT remained unchanged on average in patients with baseline CRT < 3 s (n = 7) and in all but one patient with baseline CRT ≥ 3 s in whom fluid increased CI < 15% (n = 13 "fluid non-responders"). In fluid responders with baseline CRT ≥ 3 s (n = 13), CRT decreased in 8 patients and remained unchanged in the others, exhibiting a dissociation between CI and CRT responses. The proportion of patients included > 24 h after starting norepinephrine was higher in patients with such a dissociation than in the other ones (60% vs. 0%, respectively). Norepinephrine did not change CRT significantly (except in one patient) if baseline CRT was ≥ 3 s and the increase in MAP < 15% (n = 6). In norepinephrine responders with prolonged baseline CRT (n = 11), it increased in 4 patients and remained unchanged in the other ones, which exhibited a dissociation between MAP and CRT responses. Conclusions: In septic shock patients with prolonged CRT, CRT very rarely improves with treatment when volume expansion increases cardiac output < 15% and increasing norepinephrine increases MAP < 15%. When the effects of fluid infusion on cardiac output and of norepinephrine on MAP are significant, the response of CRT is variable, as it decreases in some patients and remains stable in others which exhibit a dissociation between changes in macrohemodynamic variables and in CRT. In this regard, CRT behaves as a marker of microcirculation. Trial registration: ClinicalTrial.gov (NCT04870892). Registered January15, 2021. Ethics committee approval CE SRLF 21-25. [ABSTRACT FROM AUTHOR]

Background: The initial hemodynamic goal during septic shock resuscitation is to achieve a mean arterial pressure (MAP) above 65 mm Hg, although this does not assure a normal tissue perfusion. Capillary refill time (CRT), a marker of skin blood flow, has been validated as a marker of the reperfusion process. The aim of the study was to explore the relationship between MAP and CRT in patients in septic shock. Methods: We systematically reviewed studies which reported CRT and MAP in septic shock patients. Authors of eligible studies were asked to provide necessary data for performing a meta-correlation of Spearman's rank correlation coefficients. Subgroup analyses were performed, including studies of good quality and studies with higher/lower norepinephrine doses. Results: We identified 10 studies, comprising 917 patients. There were 5 studies considered to be of good quality. A meta-correlation showed a statistically significant but poor negative correlation between MAP and CRT (R = −0.158, range −0.221 to −0.093, P <.001, I2 = 0.0%). Subgroup analysis of best-quality studies gave similar results (R = −0.201, range −0.282 to −0.116, P <.001, I2 = 0.0%). In subanalysis concerning norepinephrine doses, no significant correlations were found. Conclusions: In patients with septic shock, there is poor inverse correlation between MAP and CRT. MAP > 65 mm Hg does not guarantee normalization of CRT. Registration code: PROSPERO: CRD42022355996. Registered on 5 September 2022. [ABSTRACT FROM AUTHOR]

To evaluate the association between capillary refill time (CRT) measured by a medical device and sepsis among patients presenting to the Emergency Department (ED). This prospective observational study enrolled adult and pediatric patients during ED triage when sepsis was considered a potential diagnosis by the triage nurse. Patients were enrolled at an academic medical center between December 2020 and June 2022. CRT was measured by a research assistant using an investigational medical device. The outcomes included sepsis and septic shock defined using sep-3 criteria, septic shock defined as IV antibiotics and a vasopressor requirement, ICU admission, and hospital mortality. Other measures included patient demographics and vital signs at ED triage. We evaluated univariate associations between CRT and sepsis outcomes. We enrolled 563 patients in the study, 48 met Sep-3 criteria, 5 met Sep-3 shock criteria, and 11 met prior septic shock criteria (IV antibiotics and vasopressors to maintain mean arterial pressure of 65). Sixteen patients were admitted to the ICU. The mean age was 49.1 years, and 51% of the cohort was female. The device measured CRT was significantly associated with the diagnosis of sepsis by sep-3 criteria (OR 1.23, 95% CI 1.06–1-43), septic shock by sep-3 criteria (OR 1.57, 95% CI 1.02–2.40), and septic shock defined as receipt of IV antibiotics and a vasopressor requirement (OR 1.37, 95% CI 1.03–1.82). Patients with CRT >3.5 s measured by the DCR device had an odds ratio of 4.67 (95%CI 1.31–16.1) of septic shock (prior definition), and an odds ratio of 3.97 (95% CI 1.99–7.92) of ICU admission, supporting the potential for the 3.5-s cutoff of the DCR measurement. CRT measured by a medical device at ED triage was associated with the diagnosis of sepsis. Objective CRT measurement using a medical device may be a relatively simple way to improve sepsis diagnosis during ED triage. [ABSTRACT FROM AUTHOR]

Capillary refill time (CRT), a costless and widely available tool, has emerged as a promising target to guide septic shock resuscitation. However, it has yet to gain universal acceptance due to its potential inter-observer variability. Standardization of CRT assessment may minimize this problem, but few studies have compared this approach with techniques that directly assess skin blood flow (SBF). Our objective was to determine if an abnormal CRT is associated with impaired SBF and microvascular reactivity in early septic shock patients. Twelve septic shock patients were subjected to multimodal perfusion and hemodynamic monitoring for 24 h. Three time-points (0, 1, and 24 h) were registered for each patient. SBF was measured by laser doppler. We performed a baseline SBF measurement and two microvascular reactivity tests: one with a thermal challenge at 44 °C and other with a vascular occlusion test. Ten healthy volunteers were evaluated to obtain reference values. The patients (median age 70 years) exhibited a 28-day mortality of 50%. Baseline CRT was 3.3 [2.7–7.3] seconds. In pooled data analysis, abnormal CRT presented a significantly lower SBF when compared to normal CRT [44 (13.3–80.3) vs 193.2 (99.4–285) APU, p = 0.0001]. CRT was strongly associated with SBF (R2 0.76, p < 0.0001). An abnormal CRT also was associated with impaired thermal challenge and vascular occlusion tests. Abnormal CRT values observed during early septic shock resuscitation are associated with impaired skin blood flow, and abnormal skin microvascular reactivity. Future studies should confirm these results. [ABSTRACT FROM AUTHOR]

Introduction: Capillary refill time (CRT) is an indicator of peripheral circulation and is recommended in the 2021 guidelines for treating and managing sepsis. Study Objective: This study developed a portable device to realize objective CRT measurement. Assuming that peripheral blood flow obstruction by the artery occlusion test (AOT) or venous occlusion test (VOT) increases the CRT, the cut-off value for peripheral circulatory failure was studied by performing a comparative analysis with CRT with no occlusion test (No OT). Methods: Fourteen (14) healthy adults (age: 20–26 years) participated in the study. For the vascular occlusion test, a sphygmomanometer was placed on the left upper arm of the participant in the supine position, and a pressure of 30mmHg higher than the systolic pressure was applied for AOT, a pressure of 60mmHg was applied for VOT, respectively, and no pressure was applied for No OT. The CRT was measured from the index finger of the participant's left hand. Results: Experimental results revealed that CRT was significantly longer in the AOT and did not differ significantly in the VOT. The cut-off value for peripheral circulatory failure was found to be 2.88 seconds based on Youden's index by using receiver operating characteristic (ROC) analysis with AOT as positive and No OT as negative. Conclusion: Significant results were obtained in a previous study on the evaluation of septic shock patients when CRT > three seconds was considered abnormal, and the cut-off value for peripheral circulatory failure in the current study validated this. [ABSTRACT FROM AUTHOR]

Multiple tissue perfusion markers are described to guide therapy in critically ill pediatric patients undergoing congenital heart surgery. Given the advantages of capillary refill time, our goal is to determine its predictive capacity for mortality and postoperative extracorporeal oxygenation requirements in congenital heart surgery and compare it to serum lactate. We conducted a prospective cohort observational study in a single high-complexity university hospital. Serum lactate and capillary refill time were measured at five predetermined time points: preoperative, immediate postoperative, 6, 12, and 24 h after the surgery. Prolonged immediate postoperative, 6 h, and 12 h capillary refill time measurements turned out to be independent risk factors for both outcomes. The capillary refill time area under the curve ranged between 0.70 and 0.80, while the serum lactate resulted between 0.79 and 0.92 for both outcomes. Both tissue perfusion markers resulted in mortality and extracorporeal oxygenation requirement predictors. Given the advantages of capillary refill time over serum lactate, a monitoring strategy including these two perfusion markers should be considered for congenital heart surgeries. [ABSTRACT FROM AUTHOR]

Ahmed Shaker,1 Ahmed Hasanin,1 Mostafa Nagy,1 Maha Mostafa,1 Ahmed Z Fouad,1 Hassan Mohamed,1 Ahmed S Abdallah,2 Mohamed Elsayad1 1Department of Anesthesia and Critical Care Medicine, Cairo University, Cairo, Egypt; 2Department of General Surgery, Cairo University, Cairo, EgyptCorrespondence: Ahmed Hasanin, Department of anesthesia and critical care medicine, Faculty of Medicine, 01 elsarayah Street, Elmanyal, Cairo, Egypt, Tel +201000365115, Fax +20224168736, Email ahmedmohamedhasanin@gmail.com

Septic shock leads to progressive hypoperfusion and tissue hypoxia. Unfortunately, numerous uncertainties exist around the best monitoring strategy, as available techniques are mere surrogates for these phenomena. Nevertheless, central venous oxygen saturation (ScvO2), venous-to-arterial CO2 gap, and lactate normalization have been fostered as resuscitation targets for septic shock. Moreover, recent evidence has challenged the central role of lactate. Following the ANDROMEDA-SHOCK trial, capillary refill time (CRT) has become a promissory target, considering the observed benefits in mortality, treatment intensity, and organ dysfunction. Interpretation of CRT within a multimodal approach may aid clinicians in guiding resuscitative interventions and stop resuscitation earlier, thus avoiding the risk of morbid fluid overload. Integrative assessment of a patient's perfusion status can be easily performed using bedside clinical tools. Based on its fast kinetics and recent supporting evidence, targeting CRT (within a holistic assessment of perfusion) may improve outcomes in septic shock resuscitation.

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)

Background: Early reversion of sepsis-induced tissue hypoperfusion is essential for survival in septic shock. However, consensus regarding the best initial resuscitation strategy is lacking given that interventions designed for the entire population with septic shock might produce unnecessary fluid administration. This article reports the rationale, study design and analysis plan of the ANDROMEDA-2 study, which aims to determine whether a peripheral perfusion-guided strategy consisting of capillary refill time-targeted resuscitation based on clinical and hemodynamic phenotypes is associated with a decrease in a composite outcome of mortality, time to organ support cessation, and hospital length of stay compared to standard care in patients with early (< 4 hours of diagnosis) septic shock. Methods: The ANDROMEDA-2 study is a multicenter, multinational randomized controlled trial. In the intervention group, capillary refill time will be measured hourly for 6 hours. If abnormal, patients will enter an algorithm starting with pulse pressure assessment. Patients with pulse pressure less than 40mmHg will be tested for fluid responsiveness and receive fluids accordingly. In patients with pulse pressure > 40mmHg, norepinephrine will be titrated to maintain diastolic arterial pressure > 50mmHg. Patients who fail to normalize capillary refill time after the previous steps will be subjected to critical care echocardiography for cardiac dysfunction evaluation and subsequent management. Finally, vasopressor and inodilator tests will be performed to further optimize perfusion. A sample size of 1,500 patients will provide 88% power to demonstrate superiority of the capillary refill time-targeted strategy. Conclusions: If hemodynamic phenotype-based, capillary refill time-targeted resuscitation demonstrates to be a superior strategy, care processes in septic shock resuscitation can be optimized with bedside tools. [ABSTRACT FROM AUTHOR]

Abstract 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.

Abstract Sepsis is one of the main reasons for intensive care unit admission and is responsible for high morbidity and mortality. The usual hemodynamic targets for resuscitation of patients with septic shock use macro-hemodynamic parameters (hearth rate, mean arterial pressure, central venous pressure). However, persistent alterations of microcirculatory blood flow despite restoration of macro-hemodynamic parameters can lead to organ failure. This dissociation between macro- and microcirculatory compartments brings a need to assess end organs tissue perfusion in patients with septic shock. Traditional markers of tissue perfusion may not be readily available (lactate) or may take time to assess (urine output). The skin, an easily accessible organ, allows clinicians to quickly evaluate the peripheral tissue perfusion with noninvasive bedside parameters such as the skin temperatures gradient, the capillary refill time, the extent of mottling and the peripheral perfusion index.

Background: Septic shock remains a significant cause of death in critically ill patients. During septic shock, some patients will retain microcirculatory disorders despite optimal hemodynamic support (i.e., fluid resuscitation, vasopressors, inotropes). Alterations in the microcirculation are a key pathophysiological factor of organ dysfunction and death in septic shock patients. Ilomedin is a prostacyclin analog with vasodilatory effect and anti-thrombotic properties (i.e., inhibition of platelet aggregation) preferentially at the microcirculatory level. We hypothesize that early utilization of intravenous Ilomedin in septic shock patients with clinical persistence of microperfusion disorders would improve the recovery of organ dysfunction.Methods: The I-MICRO trial is a multicenter, prospective, randomized, double-blinded, placebo-controlled study. We plan to recruit 236 adult patients with septic shock and persistent microcirculatory disorders (i.e., skin mottling or increased capillary refill time) despite hemodynamic support. Participants will be randomized to receive a 48-h intravenous infusion of either Ilomedin or placebo starting at the earliest 6 h and later 24 h after septic shock. The primary outcome will be the change (delta) of sequential organ failure assessment (SOFA) score between randomization and day 7. Secondary outcomes will include mean SOFA score during the first 7 days after randomization, mortality at day 28 post-randomization, number of ventilation-free survival days in the 28 days post-randomization, number of renal replacement therapy-free survival days in the 28 days post-randomization, number of vasopressor-free survival days in the 28 days post-randomization, and mottling score at day 1 after randomization.Discussion: The trial aims to provide evidence on the efficacy and safety of Ilomedin in patients with septic shock and persistent microcirculatory disorders.Trial Registration: NCT NCT03788837 . Registered on 28 December 2018. [ABSTRACT FROM AUTHOR]

Rationale: A recent randomized controlled trial showed that a peripheral perfusion-guided resuscitation strategy was associated with lower mortality and less organ dysfunction when compared with lactate-guided resuscitation strategy in patients with septic shock, but the difference in the primary outcome, 28-day mortality, did not reach the proposed statistical significancethreshold(P=0.06). We tested different analytic methods to aid in the interpretation of these results. Objectives: To reassess the results of the ANDROMEDA-SHOCK trial using both Bayesian and frequentist frameworks. Methods: All patients recruited in ANDROMEDA-SHOCK were included. Both a post hoc Bayesian analysis and a mixed logistic regression analysis were performed. The Bayesian analysis included four different priors (optimistic, neutral, null, and pessimistic) for mortality endpoints. The probability of having a Sequential Organ Failure Assessment in the lowest quartile at 72 hours was assessed using Bayesian networks. Measurements and Main Results: In the Bayesian analysis, the posterior probability that a peripheral perfusion-targeted resuscitation strategy is superior to lactate-targeted resuscitation at 28 days was above 90% for all priors; the probability ofbenefit at 90 days was above 90% for all but the pessimistic prior. Using an optimistic prior, posterior median odds ratios were 0.61 (95% credible interval, 0.41-0.90) and 0.68 (95% credible interval, 0.47-1.01) for 28-day and 90-day mortality, respectively. The comparable frequentist odds ratios for 28-day and 90-day mortality were0.61(95%confidenceinterval[CI],0.38-0.92)and0.70(95%CI, 0.45-1.08), respectively. The odds that that patients in the peripheral perfusion-targeted resuscitation arm had Sequential Organ Failure Assessmentscoresinthelowerquartileat72hourswas1.55(95%CI, 1.02-2.37). Conclusions: Peripheral perfusion-targeted resuscitation may result in lower mortality and faster resolution of organ dysfunction when compared with a lactate-targeted resuscitation strategy. [ABSTRACT FROM AUTHOR]

Objective: In the emergency department (ED), the severity assessment of shock is a fundamental step prior to the admission in the intensive care unit (ICU). As biomarkers are time consuming to evaluate the severity of micro- and macro-circulation alteration, capillary refill time and skin mottling score are two simple, available clinical criteria validated to predict mortality in the ICU. The aim of the present study is to provide clinical evidence that capillary refill time and skin mottling score assessed in the ED also predict ICU admission of patients with septic or haemorrhagic shock. Methods: This trial is an observational, non-randomised controlled study. A total of 1500 patients admitted to the ED for septic or haemorrhagic shock will be enrolled into the study. The primary outcome is the admission to the ICU. Results: The study will not impact the treatments provided to each patient. Capillary refill time and skin mottling score will not be taken into account to decide patient's treatments and/or ICU admission. Patients will be followed up during their hospital stay to determine their precise destination after the ED (home, ICU or ward) and the 28- and 90-day mortality after hospital admission. Conclusion: The results from the present study will provide clinical evidence on the correlation between the ICU admission and the capillary refill time and the skin mottling score in septic or haemorrhagic shock admitted to the ED. The aim of the present study is to provide two simple, reliable and non-invasive tools for the triage and early orientation of these patients. [ABSTRACT FROM AUTHOR]

Objectives: The early identification of septic shock patients at high risk of poor outcome is essential to early initiate optimal treatments and to decide on hospital admission. Biomarkers are often used to evaluate the severity. In prehospital settings, the availability of biomarkers, such as lactate, is restricted. In this context, clinical tools such as skin mottling score (SMS) and capillary refill time (CRT) are more suitable. In this study, we describe prehospital SMS and CRT's ability to predict mortality of patients with septic shock initially cared in the prehospital setting by a mobile intensive care unit.Methods: Patients with septic shock who received prehospital medical care admitted to the intensive care unit were retrospectively analyzed.Results: Sixty-three patients were included. The origin of sepsis was mainly pulmonary (67%). Overall mortality reached 36%. No significant difference was observed in the duration of prehospital medical care between alive and deceased patients. Mean prehospital value of SMS was 3 ± 2 and mean prehospital value of CRT was 5 ± 1 s. A significant association was found between mortality and prehospital SMS (p = 0.02, OR[CI95] = 1.50 [1.08-2.15]) and prehospital CRT (p = 0.04, OR[CI95] = 1.53 [1.04-2.37]). After adjusting for confounding factors using propensity score, the relative risk of death was 6.58 for SMS > 2 and 2.03 for CRT > 4 s.Conclusion: In this study, we report an association between prehospital SMS and CRT, and mortality of patients with septic shock. SMS and CRT are simple tools that could be used to optimize the triage and to decide early intensive care admission. [ABSTRACT FROM AUTHOR]

Copyright of Mugla Journal of Science & Technology is the property of Mugla Journal of Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Persistent hyperlactatemia is particularly difficult to interpret in septic shock. Besides hypoperfusion, adrenergic-driven lactate production and impaired lactate clearance are important contributors. However, clinical recognition of different sources of hyperlactatemia is unfortunately not a common practice and patients are treated with the same strategy despite the risk of over-resuscitation in some. Indeed, pursuing additional resuscitation in non-hypoperfusion-related cases might lead to the toxicity of fluid overload and vasoactive drugs. We hypothesized that two different clinical patterns can be recognized in septic shock patients through a multimodal perfusion monitoring. Hyperlactatemic patients with a hypoperfusion context probably represent a more severe acute circulatory dysfunction, and the absence of a hypoperfusion context is eventually associated with a good outcome. We performed a retrospective analysis of a database of septic shock patients with persistent hyperlactatemia after initial resuscitation. Results: We defined hypoperfusion context by the presence of a ScvO < 70%, or a P(cv-a)CO ≥6 mmHg, or a CRT ≥4 s together with hyperlactatemia. Ninety patients were included, of whom seventy exhibited a hypoperfusion-related pattern and 20 did not. Although lactate values were comparable at baseline (4.8 ± 2.8 vs. 4.7 ± 3.7 mmol/L), patients with a hypoperfusion context exhibited a more severe circulatory dysfunction with higher vasopressor requirements, and a trend to longer mechanical ventilation days, ICU stay, and more rescue therapies. Only one of the 20 hyperlactatemic patients without a hypoperfusion context died (5%) compared to 11 of the 70 with hypoperfusion-related hyperlactatemia (16%). Conclusions: Two different clinical patterns among hyperlactatemic septic shock patients may be identified according to hypoperfusion context. Patients with hyperlactatemia plus low ScvO, or high P(cv-a)CO, or high CRT values exhibited a more severe circulatory dysfunction. This provides a starting point to launch further prospective studies to confirm if this approach can lead to a more selective resuscitation strategy. [ABSTRACT FROM AUTHOR]

Copyright of Revista Chilena de Pediatría is the property of Revista Chilena de Pediatria and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

Rationale: A recent randomized controlled trial showed that a peripheral perfusion-guided resuscitation strategy was associated with lower mortality and less organ dysfunction when compared with lactate-guided resuscitation strategy in patients with septic shock, but the difference in the primary outcome, 28-day mortality, did not reach the proposed statistical significance threshold (P = 0.06). We tested different analytic methods to aid in the interpretation of these results.Objectives: To reassess the results of the ANDROMEDA-SHOCK trial using both Bayesian and frequentist frameworks.Methods: All patients recruited in ANDROMEDA-SHOCK were included. Both a post hoc Bayesian analysis and a mixed logistic regression analysis were performed. The Bayesian analysis included four different priors (optimistic, neutral, null, and pessimistic) for mortality endpoints. The probability of having a Sequential Organ Failure Assessment in the lowest quartile at 72 hours was assessed using Bayesian networks.Measurements and Main Results: In the Bayesian analysis, the posterior probability that a peripheral perfusion-targeted resuscitation strategy is superior to lactate-targeted resuscitation at 28 days was above 90% for all priors; the probability of benefit at 90 days was above 90% for all but the pessimistic prior. Using an optimistic prior, posterior median odds ratios were 0.61 (95% credible interval, 0.41-0.90) and 0.68 (95% credible interval, 0.47-1.01) for 28-day and 90-day mortality, respectively. The comparable frequentist odds ratios for 28-day and 90-day mortality were 0.61 (95% confidence interval [CI], 0.38-0.92) and 0.70 (95% CI, 0.45-1.08), respectively. The odds that that patients in the peripheral perfusion-targeted resuscitation arm had Sequential Organ Failure Assessment scores in the lower quartile at 72 hours was 1.55 (95% CI, 1.02-2.37).Conclusions: Peripheral perfusion-targeted resuscitation may result in lower mortality and faster resolution of organ dysfunction when compared with a lactate-targeted resuscitation strategy. [ABSTRACT FROM AUTHOR]