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.

Lower Limb Ischemia in Surgical Femoral Veno-Arterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: To analyze the incidence, clinical impact on survival, and risk factors of lower limb ischemia (LLI) of surgical peripheral femoral venoarterial extracorporeal membrane oxygenation (VA ECMO) in the current era. DESIGN: A retrospective analysis of the authors' institutional database of VA ECMO was performed. Patients were divided into 2 groups according to the occurrence of LLI. The primary endpoint was survival to hospital discharge. Risk factors of LLI were searched with multivariate analyses. SETTING: University hospital. PARTICIPANTS: Adult patients receiving peripheral VA ECMO for refractory cardiogenic shock and cardiac arrest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From January 2018 to December 2021, 188 patients (mean age: 52.0 ± 14.1 years; 63.8% male, 36.2% female) received peripheral VA ECMO. Male sex was more prevalent in the group without LLI (65.9% v 33.3%; p = 0.031). Twelve (6.4%) patients developed LLI during VA ECMO support (n = 6) or after VA ECMO removal (n = 6). Survival to hospital discharge was not statistically different between patients with and without LLI (50.0% v 48.3%; p = 0.571). Female sex patients were at increased risk for LLI (odds ratio 4.38, 95% CI 1.21-15.81; p = 0.024). CONCLUSIONS: Peripheral femoral VA ECMO through a surgical approach is associated with a low LLI rate, which does not increase the risk of in-hospital mortality. The female sex is an independent risk factor for LLI.

Central Versus Peripheral Arterial Pressure Monitoring in Patients Undergoing Cardiac Surgery: A Prospective Observational Study.

OBJECTIVE: The aortic-to-radial arterial pressure gradient is described during and after cardiopulmonary bypass (CPB), and can lead to underestimating arterial blood pressure. The authors hypothesized that central arterial pressure monitoring would be associated with lower norepinephrine requirements than radial arterial pressure monitoring during cardiac surgery. DESIGN: An observational prospective cohort with propensity score analysis. SETTING: At a tertiary academic hospital's operating room and intensive care unit (ICU). PARTICIPANTS: A total of 286 consecutive adult patients undergoing cardiac surgery with CPB (central group: 109; radial group: 177) were enrolled and analyzed. INTERVENTIONS: To explore the hemodynamic effect of the measurement site, the authors divided the cohort into 2 groups according to a femoral/axillary (central group) or radial (radial group) site of arterial pressure monitoring. MEASUREMENT AND MAIN RESULTS: The primary outcome was the intraoperative amount of norepinephrine administered. Secondary outcomes included norepinephrine-free hours and ICU-free hours at postoperative day 2 (POD2). A logistic model with propensity score analysis was built to predict central arterial pressure monitoring use. The authors compared demographic, hemodynamic, and outcomes data before and after adjustment. Central group patients had a higher European System for Cardiac Operative Risk Evaluation. (EuroSCORE) compared to the radial group-7.9 ± 14.0 versus 3.8 ± 7.0, p < 0.001. After adjustment, both groups had similar patient EuroSCORE and arterial blood pressure levels. Intraoperative norepinephrine dose regimens were 0.10 ± 0.10 µg/kg/min in the central group and 0.11 ± 0.11 µg/kg/min in the radial group (p = 0.519). Norepinephrine-free hours at POD2 were 38 ± 17 hours versus 33 ± 19 hours in central and radial groups, respectively (p = 0.034). The ICU-free hours at POD2 were greater in the central group: 18 ± 13 hours versus 13 ± 13 hours, p = 0.008. Adverse events were less frequent in the central group than in the radial group-67% versus 50%, p = 0.007. CONCLUSIONS: No differences in the norepinephrine dose regimen were found according to the arterial measurement site during cardiac surgery. However, norepinephrine use and length of stay in the ICU were shorter, and adverse events were decreased when central arterial pressure monitoring was used.

Preload Dependence Fails to Predict Hemodynamic Instability During a Fluid Removal Challenge in Children.

OBJECTIVES: Fluid overload increases morbidity and mortality in PICU patients. Active fluid removal improves the prognosis but may worsen organ dysfunction. Preload dependence in adults does predict hemodynamic instability induced by a fluid removal challenge (FRC). We sought to investigate the diagnostic accuracy of dynamic and static markers of preload in predicting hemodynamic instability and reduction of stroke volume during an FRC in children. We followed the Standards for Reporting of Diagnostic Accuracy statement to design conduct and report this study. DESIGN: Prospective noninterventional cohort study. SETTINGS: From June 2017 to April 2019 in a pediatric cardiac ICU in a tertiary hospital. PATIENTS: Patients 8 years old or younger, with symptoms of fluid overload after cardiac surgery, were studied. INTERVENTIONS: We confirmed preload dependence by echocardiography before and during a calibrated abdominal compression test. We then performed a challenge to remove 10-mL/kg fluid in less than 120 minutes with an infusion of diuretics. Hemodynamic instability was defined as a decrease of 10% of mean arterial pressure. MEASUREMENT AND MAIN RESULTS: We compared patients showing hemodynamic instability with patients remaining stable, and we built receiver operative characteristic (ROC) curves. Among 58 patients studied, 10 showed hemodynamic instability. The area under the ROC curve was 0.55 for the preload dependence test (95% CI, 0.34-0.75). Using a threshold of 10% increase in stroke volume index (SVi) during calibrated abdominal compression, the specificity was 0.30 (95% CI, 0.00-0.60) and the sensitivity was 0.77 (95% CI, 0.65-0.88). Mean arterial pressure variation and SVi variation were not correlated during fluid removal; r = 0.19; 95% CI -0.07 to 0.43; p = 0.139. CONCLUSIONS: Preload dependence is not accurate to predict hemodynamic instability during an FRC. Our data do not support a reduction in intravascular volume being mainly responsible for the reduction in arterial pressure during an FRC in children.

Veno-arterial extracorporeal membrane oxygenation for drug intoxications: A single center, 14-year experience.

BACKGROUND AND AIM OF THE STUDY: Acute cardiovascular failure remains a leading cause of death in severe poisonings. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been increasingly used as a rescue therapeutic option for those cases refractory to optimal conventional treatment. We sought to evaluate the outcomes after VA-ECMO used for drug intoxications in a single-center experience. METHODS: We performed an observational analysis of our prospective institutional database. The primary endpoint was survival to hospital discharge. RESULTS: Between January 2007 and December 2020, 32 patients (mean age: 45.4 ± 15.8 years; 62.5% female) received VA-ECMO for drug intoxication-induced refractory cardiogenic shock (n = 25) or cardiac arrest (n = 7). Seven (21.8%) patients developed lower limb ischemia during VA-ECMO support. Twenty-six (81.2%) patients were successfully weaned after a mean VA-ECMO support of 2.9 ± 1.3 days. One (3.1%) patient died after VA-ECMO weaning for multiorgan failure and survival to hospital discharge was 78.1% (n = 25). In-hospital survivors were discharged from hospital with a good neurological status. Survival to hospital discharge was not statistically different according to sex (male = 75.0% vs. female = 80.0%; p = .535), type of intoxication (single drug = 81.8% vs. multiple drugs = 76.1%; p = .544) and location of VA-ECMO implantation (within our center = 75% vs. peripheral hospital using our Mobile Unit of Mechanical Circulatory Support = 100%; p = .352). Survival to hospital discharge was significantly lower in patients receiving VA-ECMO during on-going cardiopulmonary resuscitation (42.8% vs. 88.0%; p = .026). CONCLUSIONS: VA-ECMO appears to be a feasible therapeutic option with a satisfactory survival rate and acceptable complications rate in poisonings complicated by refractory cardiogenic shock or cardiac arrest.

Effects of methylene blue on microcirculatory alterations following cardiac surgery: A prospective cohort study.

BACKGROUND: Methylene blue is used as rescue therapy to treat catecholamine-refractory vasoplegic syndrome after cardiac surgery. However, its microcirculatory effects remain poorly documented. OBJECTIVE: We aimed to study microcirculatory abnormalities in refractory vasoplegic syndrome following cardiac surgery with cardiopulmonary bypass and assess the effects of methylene blue. DESIGN: A prospective open-label cohort study. SETTING: 20-Bed ICU of a tertiary care hospital. PATIENTS: 25 Adult patients receiving 1.5 mg kg-1 of methylene blue intravenously for refractory vasoplegic syndrome (defined as norepinephrine requirement more than 0.5 µg kg-1 min-1) to maintain mean arterial pressure (MAP) more than 65 mmHg and cardiac index (CI) more than 2.0 l min-1 m-2. MAIN OUTCOME MEASURES: Complete haemodynamic set of measurements at baseline and 1 h after the administration of methylene blue. Sublingual microcirculation was investigated by sidestream dark field imaging to obtain microvascular flow index (MFI), total vessel density, perfused vessel density and heterogeneity index. Microvascular reactivity was assessed by peripheral near-infrared (IR) spectroscopy combined with a vascular occlusion test. We also performed a standardised measurement of capillary refill time. RESULTS: Despite normalised CI (2.6 [2.0 to 3.8] l min-1 m-2) and MAP (66 [55 to 76] mmHg), patients with refractory vasoplegic syndrome showed severe microcirculatory alterations (MFI < 2.6). After methylene blue infusion, MFI significantly increased from 2.0 [0.1 to 2.5] to 2.2 [0.2 to 2.8] (P = 0.008), as did total vessel density from 13.5 [8.3 to 18.5] to 14.9 [10.1 to 14.7] mm mm-2 (P = 0.02) and perfused vessel density density from 7.4 [0.1 to 11.5] to 9.1 [0 to 20.1] mm mm-2 (P = 0.02), but with wide individual variation. Microvascular reactivity assessed by tissue oxygen resaturation speed also increased from 0.5 [0.1 to 1.8] to 0.7 [0.1 to 2.7]% s-1 (P = 0.002). Capillary refill time remained unchanged throughout the study. CONCLUSION: In refractory vasoplegic syndrome following cardiac surgery, we found microcirculatory alterations despite normalised CI and MAP. The administration of methylene blue could improve microvascular perfusion and reactivity, and partially restore the loss of haemodynamic coherence. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04250389.

Prediction of intraoperative hypotension from the linear extrapolation of mean arterial pressure.

BACKGROUND: Hypotension prediction index (HPI) software is a proprietary machine learning-based algorithm used to predict intraoperative hypotension (IOH). HPI has shown superiority in predicting IOH when compared to the predictive value of changes in mean arterial pressure (ΔMAP) alone. However, the predictive value of ΔMAP alone, with no reference to the absolute level of MAP, is counterintuitive and poor at predicting IOH. A simple linear extrapolation of mean arterial pressure (LepMAP) is closer to the clinical approach. OBJECTIVES: Our primary objective was to investigate whether LepMAP better predicts IOH than ΔMAP alone. DESIGN: Retrospective diagnostic accuracy study. SETTING: Two tertiary University Hospitals between May 2019 and December 2019. PATIENTS: A total of 83 adult patients undergoing high risk non-cardiac surgery. DATA SOURCES: Arterial pressure data were automatically extracted from the anaesthesia data collection software (one value per minute). IOH was defined as MAP < 65 mmHg. ANALYSIS: Correlations for repeated measurements and the area under the curve (AUC) from receiver operating characteristics (ROC) were determined for the ability of LepMAP and ΔMAP to predict IOH at 1, 2 and 5 min before its occurrence (A-analysis, using the whole dataset). Data were also analysed after exclusion of MAP values between 65 and 75 mmHg (B-analysis). RESULTS: A total of 24 318 segments of ten minutes duration were analysed. In the A-analysis, ROC AUCs to predict IOH at 1, 2 and 5 min before its occurrence by LepMAP were 0.87 (95% confidence interval, CI, 0.86 to 0.88), 0.81 (95% CI, 0.79 to 0.83) and 0.69 (95% CI, 0.66 to 0.71) and for ΔMAP alone 0.59 (95% CI, 0.57 to 0.62), 0.61 (95% CI, 0.59 to 0.64), 0.57 (95% CI, 0.54 to 0.69), respectively. In the B analysis for LepMAP these were 0.97 (95% CI, 0.9 to 0.98), 0.93 (95% CI, 0.92 to 0.95) and 0.86 (95% CI, 0.84 to 0.88), respectively, and for ΔMAP alone 0.59 (95% CI, 0.53 to 0.58), 0.56 (95% CI, 0.54 to 0.59), 0.54 (95% CI, 0.51 to 0.57), respectively. LepMAP ROC AUCs were significantly higher than ΔMAP ROC AUCs in all cases. CONCLUSIONS: LepMAP provides reliable real-time and continuous prediction of IOH 1 and 2 min before its occurrence. LepMAP offers better discrimination than ΔMAP at 1, 2 and 5 min before its occurrence. Future studies evaluating machine learning algorithms to predict IOH should be compared with LepMAP rather than ΔMAP.

Capillary refill time for the management of acute circulatory failure: a survey among pediatric and adult intensivists.

INTRODUCTION: Recent studies have shown the prognostic value of capillary refill time (CRT) and suggested that resuscitation management guided by CRT may reduce morbidity and mortality in patients with septic shock. However, little is known about the current use of CRT in routine clinical practice. This study aimed to assess the modalities of CRT use among French adult and pediatric intensivists. METHODS: A cross-sectional survey exploring CRT practices in acute circulatory failure was performed. The targeted population was French adult and pediatric intensivists (SFAR and GFRUP networks). An individual invitation letter including a survey of 32 questions was emailed twice. Descriptive and analytical statistics were performed. RESULTS: Among the 6071 physicians who received the letter, 418 (7%) completed the survey. Among all respondents, 82% reported using CRT in routine clinical practice, mainly to diagnose acute circulatory failure, but 45% did not think CRT had any prognostic value. Perfusion goal-directed therapy based on CRT was viewed as likely to improve patient outcome by 37% of respondents. The measurement of CRT was not standardized as the use of a chronometer was rare (3%) and the average of multiple measurements rarely performed (46%). Compared to adult intensivists, pediatric intensivists used CRT more frequently (99% versus 76%) and were more confident in its diagnostic value and its ability to guide treatment. CONCLUSION: CRT measurement is widely used by intensivists in patients with acute circulatory failure but most often in a non-standardized way. This may lead to a misunderstanding of CRT reliability and clinical usefulness.

Extracorporeal life support in the multidisciplinary management of cardiogenic shock complicating acute myocardial infarction.

OBJECTIVES: To analyze the results of extracorporeal life support (ECLS) for cardiogenic shock complicating acute myocardial infarction (AMI) in a single-center experience. BACKGROUND: Cardiogenic shock is still a leading cause of death for AMI. Conventional management carries mortality rates exceeding 50%. ECLS may be considered as a bridge to decision in the setting of AMI complicated by cardiogenic shock not responsive to standard management. METHODS: We performed an observational analysis of our local database. The primary end-point was survival to hospital discharge. All variables were compared between survivors and nonsurvivors. RESULTS: Between January 2007 and December 2017, 56 patients were supported for cardiogenic shock complicating AMI. The mean age was 56.7 years and 89.3% were males. Baseline characteristics were comparable between both groups. Of the 50 primary percutaneous coronary interventions that were attempted, 44 (88.0%) were successful. Twenty-three (41.1%) patients died during ECLS support. The complications' rate during ECLS support was comparable between both groups. Twenty-eight (50%) patients were successfully weaned from ECLS after a mean support of 8.7 days. Eight (14.3%) patients eventually died after weaning before hospital discharge. Five (8.9%) patients could not be weaned from ECLS and were switched to a long-term mechanical circulatory support. Overall survival to hospital discharge was 41.1% (n = 23). Eighteen (32.1%) patients were alive after a mean follow-up of 38.0 ± 29.9 (range, 4.2-95.4) months. CONCLUSIONS: ECLS should be considered as a therapeutic solution in the management of AMI-related cardiogenic shock with a satisfactory short- and long-term survival.

Improving the prognostic value of ∆PCO2 following cardiac surgery: a prospective pilot study.

Conflicting results have been published on prognostic significance of central venous to arterial PCO2 difference (∆PCO2) after cardiac surgery. We compared the prognostic value of ∆PCO2 on intensive care unit (ICU) admission to an original algorithm combining ∆PCO2, ERO2 and lactate to identify different risk profiles. Additionally, we described the evolution of ∆PCO2 and its correlations with ERO2 and lactate during the first postoperative day (POD1). In this monocentre, prospective, and pilot study, 25 patients undergoing conventional cardiac surgery were included. Central venous and arterial blood gases were collected on ICU admission and at 6, 12 and 24 h postoperatively. High ∆PCO2 (≥ 6 mmHg) on ICU admission was found to be very frequent (64% of patients). Correlations between ∆PCO2 and ERO2 or lactate for POD1 values and variations were weak or non-existent. On ICU admission, a high ∆PCO2 did not predict a prolonged ICU length of stay (LOS). Conversely, a significant increase in both ICU and hospital LOS was observed in high-risk patients identified by the algorithm: 3.5 (3.0-6.3) days versus 7.0 (6.0-8.0) days (p = 0.01) and 12.0 (8.0-15.0) versus 8.0 (8.0-9.0) days (p < 0.01), respectively. An algorithm incorporating ICU admission values of ∆PCO2, ERO2 and lactate defined a high-risk profile that predicted prolonged ICU and hospital stays better than ∆PCO2 alone.

Capillary refill time variation induced by passive leg raising predicts capillary refill time response to volume expansion.

BACKGROUND: A peripheral perfusion-targeted resuscitation during early septic shock has shown encouraging results. Capillary refill time, which has a prognostic value, was used. Adding accuracy and predictability on capillary refill time (CRT) measurement, if feasible, would benefit to peripheral perfusion-targeted resuscitation. We assessed whether a reduction of capillary refill time during passive leg raising (ΔCRT-PLR) predicted volume-induced peripheral perfusion improvement defined as a significant decrease of capillary refill time following volume expansion. METHODS: Thirty-four patients with acute circulatory failure were selected. Haemodynamic variables, metabolic variables (PCO2gap), and four capillary refill time measurements were recorded before and during a passive leg raising test and after a 500-mL volume expansion over 20 min. Receiver operating characteristic curves were built, and areas under the curves were calculated (ROCAUC). Confidence intervals (CI) were performed using a bootstrap analysis. We recorded mortality at day 90. RESULTS: The least significant change in the capillary refill time was 25% [95% CI, 18-30]. We defined CRT responders as patients showing a reduction of at least 25% of capillary refill time after volume expansion. A decrease of 27% in ΔCRT-PLR predicted peripheral perfusion improvement with a sensitivity of 87% [95% CI, 73-100] and a specificity of 100% [95% CI, 74-100]. The ROCAUC of ΔCRT-PLR was 0.94 [95% CI, 0.87-1.0]. The ROCAUC of baseline capillary refill time was 0.73 [95% CI, 0.54-0.90] and of baseline PCO2gap was 0.79 [0.61-0.93]. Capillary refill time was significantly longer in non-survivors than in survivors at day 90. CONCLUSION: ΔCRT-PLR predicted peripheral perfusion response following volume expansion. This simple low-cost and non-invasive diagnostic method could be used in peripheral perfusion-targeted resuscitation protocols. TRIAL REGISTRATION: CPP Lyon Sud-Est II ANSM: 2014-A01034-43 Clinicaltrial.gov, NCT02248025 , registered 13th of September 2014.

Microvascular effects of intravenous esmolol in patients with normal cardiac function undergoing postoperative atrial fibrillation: a prospective pilot study in cardiothoracic surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is commonplace after cardiothoracic surgery. A rate control strategy using short-acting beta blockers is recommended as a first-line therapy in patients without hemodynamic instability. Microcirculatory effects of POAF and esmolol have not yet been investigated. We hypothesized that POAF without hemodynamic instability would induce microvascular dysfunction which could be reversed by intravenous esmolol. METHODS: Twenty-five cardiothoracic surgical patients with POAF were included in the study. Microcirculation was assessed by peripheral near-infrared spectroscopy (NIRS) in association with a vascular occlusion test (VOT) before esmolol infusion, during incremental doses of esmolol (25, 50, 100, and 200 µg/kg/min), and after a return to sinus rhythm. Esmolol was given to control heart rate to between 60 and 90 beats/min. Regional tissue oxygen saturation variables (StO2, StO2 min, StO2 max, and ∆StO2) and desaturation/resaturation speeds during VOT were recorded to evaluate the microcirculation. RESULTS: StO2 and resaturation speed were significantly improved when POAF returned to sinus rhythm (StO2 64% ± 6 versus 67% ± 6, P < 0.01; resaturation speed 0.53%/s (0.42-0.97) versus 0.66%/s (0.51-1.04), P = 0.020). ∆StO2 was significantly decreased after a return to sinus rhythm (7.9% ± 4.8 versus 6.1% ± 4.7, P = 0.026). During esmolol infusion, we found a significant decrease in both heart rate (P < 0.001) and blood pressure (P < 0.001), and a non-significant dose-dependent increase in StO2 (P = 0.081) and resaturation speed (P = 0.087). CONCLUSION: POAF without hemodynamic instability is associated with significant impairment in the microcirculation which could be partially reversed by intravenous esmolol.