Perspectives for capillary refill time in clinical practice for sepsis.

BACKGROUND: Capillary refill time (CRT) is defined as the time taken for color to return to an external capillary bed after pressure is applied to cause blanching. Recent studies demonstrated the benefits of CRT in guiding fluid therapy for sepsis. However, lack of consistency among physicians in how to perform and interpret CRT has led to a low interobserver agreement for this assessment tool, which prevents its availability in sepsis clinical settings. OBJECTIVE: To give physicians a concise overview of CRT and explore recent evidence on its reliability and value in the management of sepsis. RESEARCH DESIGN: A narrative review. RESULTS: This narrative review summarizes the factors affecting CRT values, for example, age, sex, temperature, light, observation techniques, work experience, training level and differences in CRT measurement methods. The methods of reducing the variability of CRT are synthesized. Based on studies with highly reproducible CRT measurements and an excellent inter-rater concordance, we recommend the standardized CRT assessment method. The threshold of normal CRT values is discussed. The application of CRT in different phases of sepsis management is summarized. CONCLUSIONS: Recent data confirm the value of CRT in critically ill patients. CRT should be detected by trained physicians using standardized methods and reducing the effect of ambient-related factors. Its association with severe infection, microcirculation, tissue perfusion response, organ dysfunction and adverse outcomes makes this approach a very attractive tool in sepsis. Further studies should confirm its value in the management of sepsis. IMPLICATIONS FOR CLINICAL PRACTICE: As a simple assessment, CRT deserves more attention even though it has not been widely applied at the bedside. CRT could provide nursing staff with patient's microcirculatory status, which may help to develop individualized nursing plans and improve the patient's care quality and treatment outcomes.

Quantitative Capillary Refill Time with image-based finger force estimation.

Skin color observation provides a simple and non-invasive method to estimate the health status of patients. Capillary Refill Time (CRT) is widely used as an indicator of pathophysiological conditions, especially in emergency patients. While the measurement of CRT is easy to perform, its evaluation is highly subjective. This study proposes a method to aid quantified CRT measurement using an RGB camera. The procedure consists in applying finger compression to the forearm, and the CRT is calculated based on the skin color change after the pressure release. We estimate compression applied by a finger from its fingernail color change during compression. Our study shows a step towards camera-based quantitative CRT for untrained individuals.

Capillary refill time response to a fluid challenge or a vasopressor test: an observational, proof-of-concept study.

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.

Skin mottling score assesses peripheral tissue hypoperfusion in critically ill patients following cardiac surgery.

BACKGROUND: Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. METHODS: Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. RESULTS: Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p < 0.001). The occurrences of skin mottling were higher in hypotension population and shock population, reaching 5.6% and 15.7%, respectively. The AUROC for SMS to identify peripheral hypoperfusion was 0.64, 0.68, and 0.81 in the overall, hypotension, and shock populations, respectively. The optimal SMS threshold was 1, which corresponded to specificities of 98, 97 and 91 and sensitivities of 29, 38 and 67 in the three populations (overall, hypotension and shock). The correlation of UO, lactate, CRT and vasopressor dose with SMS was significant, among them, UO and CRT were identified as two major factors associated with the presence of skin mottling. CONCLUSION: In critically ill patients following cardiac surgery, SMS is a very specific yet less sensitive parameter for detecting peripheral tissue hypoperfusion.

Association between early manifestations of infection or sepsis and prognosis in a high complexity hospital in the city of Medellín.

OBJECTIVE: To identify the first symptoms and signs of patients with suspected infection or sepsis and their association with the composite outcome of admission to the Intensive Care Unit (ICU) or mortality. DESIGN: Prospective cohort study between June 2019 and March 2020. SETTING: Hospital Universitario San Vicente Fundación, Colombia. PATIENTS: Over 18 years of age with suspicion or confirmation of sepsis, which required hospitalization. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Symptoms and signs associated with infection, with their time of evolution, specified in the study. RESULTS: From 1005 eligible patients, 261 were included. After multivariable adjustment with a logistic regression model, the main factors for ICU admission or mortality were heart rate (OR 1.04 with 95% CI 1.04-3.7), respiratory rate (OR 1.19 with 95% CI 1.0-1.4) and capillary refill time (OR 3.4 with 95% CI 1.9-6.1). CONCLUSIONS: Heart rate, respiratory rate, and capillary refill may behave as early predictors of ICU admission and mortality in cases of sepsis.

Prolonged capillary refill time and short-term mortality of critically ill patients: A meta-analysis.

BACKGROUND: Prolonged capillary refill time (CRT) is an indicator of poor peripheral perfusion. The aim of the systematic review and meta-analysis was to evaluate the association of prolonged CRT and mortality of critically ill patients. METHODS: To achieve the objective of this meta-analysis, we conducted a thorough search of PubMed, Embase, Cochrane Library, and the Web of Science to identify relevant observational studies with longitudinal follow-up. The Cochrane Q test was utilized to assess between-study heterogeneity, and the I2 statistic was calculated to estimate the degree of heterogeneity. We employed random-effects models to combine the outcomes, considering the potential influence of heterogeneity. RESULTS: Eleven studies, encompassing 11,659 critically ill patients were included. During follow-up durations within hospitalization to 3 months, 1247 (10.7%) patients died. The pooled results indicated that a prolonged CRT at early phase of admission was significantly associated with an increased risk of all-cause mortality (risk ratio [RR]: 1.73, 95% confidence interval [CI]: 1.39 to 2.16, p < 0.001; I2 = 60%). Subgroup analyses showed that the association was not significantly modified by study design (prospective or retrospective), etiology of diseases (infection, non-infection, or mixed), or cutoff of CRT (>3 s, 3.5 s, or 4 s). The association between CRT and mortality was weaker in studies with multivariate analysis (RR: 1.43, 95% CI: 1.27 to 1.60, p < 0.001; I2 = 0%) as compared to that derived from studies of univariate analysis (RR: 6.27, 95% CI: 3.29 to 11.97, p < 0.001; I2 = 0%). CONCLUSIONS: Prolonged CRT at admission may be a predictor of increased short-term mortality of critically ill patients.

Capillary refill time assessment after fluid challenge in patients on venoarterial extracorporeal membrane oxygenation: A retrospective study.

BACKGROUND: Monitoring fluid therapy is challenging in patients assisted with Veno-arterial ECMO. The aim of our study was to evaluate the usefulness of capillary refill time to assess the response to fluid challenge in patients assisted with VA-ECMO. METHODS: Retrospective monocentric study in a cardiac surgery ICU. We assess fluid responsiveness after a fluid challenge in patients on VA-ECMO. We recorded capillary refill time before and after fluid challenge and the evolution of global hemodynamic parameters. RESULTS: A total of 27 patients were included. The main indications for VA-ECMO were post-cardiotomy cardiogenic shock (44%). Thirteen patients (42%) were responders and 14 non-responders (58%). In the responder group, the index CRT decreased significantly (1.7 [1.5; 2.1] vs. 1.2 [1; 1.3] s; p = 0.01), whereas it remained stable in the non-responder group (1.4 [1.1; 2.5] vs. 1.6 [0.9; 1.9] s; p = 0.22). Diagnosis performance of CRT variation to assess response after fluid challenge shows an AUC of 0.68 (p = 0.10) with a sensitivity of 79% [95% CI, 52-92] and a specificity of 69% [95% CI, 42-87], with a threshold at 23%. CONCLUSION: In patients treated with VA-ECMO index capillary refill time is a reliable tool to assesses fluid responsiveness. SPECIALTY: Critical care, Cardiac surgery, ECMO.

The use of thermal imaging for evaluation of peripheral tissue perfusion in surgical patients with septic shock.

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%.

Albumin versus saline infusion for sepsis-related peripheral tissue hypoperfusion: a proof-of-concept prospective study.

BACKGROUND: Albumin has potential endothelial protective effects through antioxidant and anti-inflammatory properties. However, the effect of albumin on peripheral tissue perfusion in human sepsis remains poorly known. METHODS: Bi-centric prospective study included patients with sepsis with or without shock and prolonged CRT > 3 s despite initial resuscitation. Clinicians in charge of the patients were free to infuse either saline 500 mL or human serum albumin 20% 100 mL over 15 min. Global hemodynamic parameters as well as peripheral tissue perfusion were analyzed after 1 (H1) and 4 h (H4). The primary endpoint was CRT normalization (< 3 s) at H1. RESULTS: 62 patients were screened, and 50 patients (13 sepsis and 37 septic shock) were included, 21 in the saline group and 29 in the albumin group. SOFA score was 8 [5-11], and SAPS II was 53 [45-70]. Median age was 68 [60-76] years with a higher proportion of men (74%). The primary sources of infection were respiratory (54%) and abdominal (24%). At baseline, comorbidities, clinical and biological characteristics were similar between groups. At H1, CRT normalization (< 3 s) was more frequent in patients receiving albumin as compared to patients treated by saline (63 vs 29%, P = 0.02). The decrease in fingertip CRT was more important in the albumin group when compared to saline group (- 1.0 [- 0.3; - 1.5] vs - 0.2 [- 0.1; - 1.1] seconds, P = 0.04) as well as decrease in mottling score. At H4, beneficial effects of albumin on peripheral tissue perfusion were maintained and urinary output trended to be higher in the albumin group (1.1 [0.5-1.8] vs 0.7 [0.5-0.9] ml/kg/h, P = 0.08). Finally, arterial lactate level did not significantly change between H0 and H4 in the saline group but significantly decreased in the albumin group (P = 0.03). CONCLUSION: In patients with resuscitated sepsis, albumin infusion might lead to greater improvement of tissue hypoperfusion compared to saline. CLINICALTRIALS: gov Identifier: NCT05094856.

Effect of Respiratory Failure on Peripheral and Organ Perfusion Markers in Severe COVID-19: A Prospective Cohort Study.

Microvascular dysfunction and inflammation caused by COVID-19 disrupt organ function. The study aimed to investigate the association between the severity of SARS-CoV-2 pneumonia and peripheral and organ perfusion as a consequence of altered microcirculation. A total of 116 patients hospitalized due to severe COVID-19 were enrolled in the study. On admission, the patients underwent a Capillary Refill Time (CRT) examination, finger oxygen saturation measurement, thermal imaging of the hand (FIT), and a kidney Doppler ultrasound. Medical data were collected from the medical history. From the evaluated perfusion parameters, only renal cortex perfusion (RCP) was substantially correlated with the CT score (p < 0.010). The peripheral perfusion parameters of Sat., FIT, CRT, and RCP correlated with the ARDS stages (p = 0.0021; p = 0.038; p < 0.0006; p < 0.0002, respectively). The Oxygenation Ratio value (p < 0.001) was significantly associated with all the perfusion parameters (saturation, CRT, FIT, and RCP) in the multivariable regression analysis model. According to the stepwise retrograde regression analysis, RCP was an independent parameter linked with the Oxygenation Ratio (p < 0.001). Severe COVID-19 can result in microvascular dysfunction influencing peripheral and organ perfusion, which can be measured with various methods. The staging of COVID-19 assessed by CT and the Oxygenation Ratio correlates with RCP, CRT, FIT, and oxygen saturation.

Towards the personalization of septic shock resuscitation: the fundamentals of ANDROMEDA-SHOCK-2 trial.

Septic shock is a highly lethal and prevalent disease. Progressive circulatory dysfunction leads to tissue hypoperfusion and hypoxia, eventually evolving to multiorgan dysfunction and death. Prompt resuscitation may revert these pathogenic mechanisms, restoring oxygen delivery and organ function. High heterogeneity exists among the determinants of circulatory dysfunction in septic shock, and current algorithms provide a stepwise and standardized approach to conduct resuscitation. This review provides the pathophysiological and clinical rationale behind ANDROMEDA-SHOCK-2, an ongoing multicenter randomized controlled trial that aims to compare a personalized resuscitation strategy based on clinical phenotyping and peripheral perfusion assessment, versus standard of care, in early septic shock resuscitation.

Risk factors for poor performance in finger cuff non-invasive monitoring of arterial pressure: A prospective multicenter study.

BACKGROUND: Compared to the invasive technique, non-invasive monitoring of arterial pressure favors easier and faster implementation while potentially sacrificing some reliability. This may be particularly true for the Clearsight™ system (Edwards Lifesciences), which enables continuous monitoring. We evaluated the risk factors for its poor performance. METHODS: Patients with an arterial catheter and stable mean arterial pressure (MAP) over a 5-min period were included. Six pairs of invasive and Clearsight measurements of MAP were collected and the bias between the two techniques was calculated. Poor performance of the Clearsight™ system was defined as either a failure to measure and display MAP or displaying an erroneous MAP (individual bias > 5 mmHg). Fingertip perfusion was assessed using the plethysmographic perfusion index (PI) and the capillary refill time (CRT). RESULTS: Among 152 ICU patients (MAP of 81 ± 14 mmHg, norepinephrine in 78 [51%]), 78 (51%) experienced a poor performance of the Clearsight™ system: failure to display MAP in 19 (13%) patients, and erroneous value displayed in 59 (44%). In multivariate analysis, PI ≤ 0.85% (adjusted odds ratio [aOR] = 2.94 [95% confidence interval (95%CI):1.34;6.45]), CRT > 4 s (aOR = 5.28 [95%CI 1.39;20.05]), and the presence of hand edema (aOR = 2.06 [95%CI 1.01;4.21]) were associated with a higher likelihood of poor performance. Cardiac arrhythmia (aOR = 1.39 [95%CI 0.64;3.02]) and other tested variables were not associated with poor performance. CONCLUSIONS: Half of the included patients exhibited poor Clearsight™ system performance. Our results caution against using finger cuff arterial pressure monitoring in patients with low PI (≤0.85%), protracted CRT (>4 s), or hand edema. REGISTRATION: ClinicalTrials.gov, NCT04269382, Dr. G. Muller, February 13, 2020. https://classic. CLINICALTRIALS: gov/ct2/show/NCT04269382.

Intraobserver and interobserver reliability of standardized capillary refill time in dogs is high following observer training.

OBJECTIVE: To assess intraobserver and interobserver reliability of capillary refill time (CRT) measurement in dogs using a standardized technique after training. ANIMALS: 20 dogs presented to the emergency room. METHODS: Dogs presented to the emergency room were prospectively recruited. Using a timing device and standardized technique, CRT was measured at the oral mucosa of the inner lip. Measurements were performed by 2 emergency and critical care residents (observer 1 [Ob1] and observer 2 [Ob2]) and repeated 3 times by each observer for each dog. CRT values and signalment were recorded. Intraobserver and interobserver reliability were analyzed by calculation of the coefficient of variation (CV%), intraclass correlation coefficient (ICC), and minimal detectable difference. Reliability was considered high if CV% was lower than 10% and ICC was between 0.9 and 1. RESULTS: Median CRT for Ob1 was 1.22 seconds and for Ob2 was 1.19 seconds. Intraobserver reliability was high, evidenced by a median CV% of 6.2% (range, 1.0% to 18.6%) and 9.5% (range, 1.3% to 22.6%) and an ICC of 0.97 (95% CI, 0.94 to 0.99) and 0.95 (95% CI, 0.90 to 0.98) for Ob1 and Ob2, respectively. Between observers, the CV% was 4.4% (range, 0.8% to 17.5%) and the ICC was 0.98 (95% CI, 0.94 to 0.99), indicating high interobserver reliability. The minimal detectable differences for intraobserver and interobserver were 0.30 and 0.34 seconds, respectively. CLINICAL RELEVANCE: The reported high reliability of CRT despite its subjective nature enhances its usefulness in daily practice. However, further research on the validity of CRT is warranted.

Mottling in Septic Shock: Ethnicity and Skin Color Matter.

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. How to cite this article: Jog SA, Narasimhan VL, Rajhans PA, Akole PV, Pawar B, Bhurke B, et al. Mottling in Septic Shock: Ethnicity and Skin Color Matter. Indian J Crit Care Med 2023;27(12):902-909.

Prognostic value of capillary refill time in adult patients: a systematic review with meta-analysis.

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.

Effect on capillary refill time of volume expansion and increase of the norepinephrine dose in patients with septic shock.

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.

Skin-color-independent robust assessment of capillary refill time.

Capillary Refill Time (CRT) assesses peripheral perfusion in resource-limited settings. However, the repeatability and reproducibility of CRT measurements are limited for individuals with darker skin. This paper presents quantitative CRT measurements demonstrating good performance and repeatability across all Fitzpatrick skin phototypes. The study involved 22 volunteers and utilized controlled compression at 7 kPa, an RGB video camera, and cocircular polarized white LED light. CRT was determined by calculating the time constant of an exponential regression applied to the mean pixel intensity of the green (G) channel. An adaptive algorithm identifies the optimal regression region for noise reduction, and flags inappropriate readings. The results indicate that 80% of the CRT readings fell within a 20% range of the expected CRT value. The repetition standard deviation was 17%. These findings suggest the potential for developing reliable and reproducible quantitative CRT methods for robust measurements in patient triage, monitoring, and telehealth applications.

Hypoperfusion context as a predictor of 28-d all-cause mortality in septic shock patients: A comparative observational study.

BACKGROUND: As per the latest Surviving Sepsis Campaign guidelines, fluid resuscitation should be guided by repeated measurements of blood lactate levels until normalization. Nevertheless, raised lactate levels should be interpreted in the clinical context, as there may be other causes of elevated lactate levels. Thus, it may not be the best tool for real-time assessment of the effect of hemodynamic resuscitation, and exploring alternative resuscitation targets should be an essential research priority in sepsis. AIM: To compare the 28-d mortality in two clinical patterns of septic shock: hyperlactatemic patients with hypoperfusion context and hyperlactatemic patients without hypoperfusion context. METHODS: This prospective comparative observational study carried out on 135 adult patients with septic shock that met Sepsis-3 definitions compared patients with hyperlactatemia in a hypoperfusion context (Group 1, n = 95) and patients with hyperlactatemia in a non-hypoperfusion context (Group 2, n = 40). Hypoperfusion context was defined by a central venous saturation less than 70%, central venous-arterial PCO2 gradient [P(cv-a)CO2] ≥ 6 mmHg, and capillary refilling time (CRT) ≥ 4 s. The patients were observed for various macro and micro hemodynamic parameters at regular intervals of 0 h, 3 h, and 6 h. All-cause 28-d mortality and all other secondary objective parameters were observed at specified intervals. Nominal categorical data were compared using the χ2 or Fisher's exact test. Non-normally distributed continuous variables were compared using the Mann-Whitney U test. Receiver operating characteristic curve analysis with the Youden index determined the cutoff values of lactate, CRT, and metabolic perfusion parameters to predict the 28-d all-cause mortality. A P value of < 0.05 was considered significant. RESULTS: Patient demographics, comorbidities, baseline laboratory, vital parameters, source of infection, baseline lactate levels, and lactate clearance at 3 h and 6 h, Sequential Organ Failure scores, need for invasive mechanical ventilation, days on mechanical ventilation, and renal replacement therapy-free days within 28 d, duration of intensive care unit stay, and hospital stay were comparable between the two groups. The stratification of patients into hypoperfusion and non-hypoperfusion context did not result in a significantly different 28-d mortality (24% vs 15%, respectively; P = 0.234). However, the patients within the hypoperfusion context with high P(cv-a)CO2 and CRT (P = 0.022) at baseline had significantly higher mortality than Group 2. The norepinephrine dose was higher in Group 1 but did not achieve statistical significance with a P > 0.05 at all measured intervals. Group 1 had a higher proportion of patients requiring vasopressin and the mean vasopressor-free days out of the total 28 d were lower in patients with hypoperfusion (18.88 ± 9.04 vs 21.08 ± 8.76; P = 0.011). The mean lactate levels and lactate clearance at 3 h and 6 h, CRT, P(cv-a)CO2 at 0 h, 3 h, and 6 h were found to be associated with 28-d mortality in patients with septic shock, with lactate levels at 6 h having the best predictive value (area under the curve lactate at 6 h: 0.845). CONCLUSION: Septic shock patients fulfilling the hypoperfusion and non-hypoperfusion context exhibited similar 28-d all-cause hospital mortality, although patients with hypoperfusion displayed a more severe circulatory dysfunction. Lactate levels at 6 h had a better predictive value in predicting 28-d mortality than other parameters. Persistently high P(cv-a)CO2 (> 6 mmHg) or increased CRT (> 4 s) at 3 h and 6 h during early resuscitation can be a valuable additional aid for prognostication of septic shock patients.

Hemodynamics and cutaneous microcirculation during induction of general anesthesia with and without esketamine.

OBJECTIVE: Currently, there are limited data on the effect of macrocirculatory hemodynamic changes on human microcirculation, especially during the induction of general anesthesia (GA). METHODS: We performed a non-randomized observational trial on patients receiving GA for elective surgery. In the control group (CG), for GA induction sufentanil, propofol, and rocuronium was administered. Patients assigned to the esketamine group (EG) received additional esketamine for GA induction. Invasive blood pressure (IBP) and pulse contour cardiac output (CO) measurement were performed continuously. Microcirculation was assessed using cutaneous Laser Doppler Flowmetry (forehead and sternum LDF), peripheral and central Capillary Refill Time (pCRT, cCRT), as well as brachial temperature gradient (Tskin-diff) at baseline, 5, 10 and 15 minutes after induction of GA. RESULTS: 42 patients were included in the analysis (CG n = 22, EG n = 20). pCRT, cCRT, Tskin-diff, forehead and sternum LDF decreased following GA induction in both groups. IBP and CO were significantly more stable in esketamine group. However, the changes in the microcirculatory parameters were not significantly different between the groups. CONCLUSIONS: The addition of esketamine for GA induction warranted better hemodynamic stability for the first five minutes, but had no significant effect on any of the cutaneous microcirculatory parameters measured.

Cut-Off Value of Capillary Refill Time for Peripheral Circulatory Failure Diagnosis.

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.