Sepsis remains a significant and difficult diagnosis in US Emergency Departments and Intensive Care Units.

The objective of this scoping review was to understand the state of the literature regarding the performance of Capillary Refill Time [CRT] as a method to assess circulatory dysfunction in sepsis.

This study followed PRISMA Guidelines for Scoping Reviews. Included studies used CRT as a physical exam finding 'measuring the time of return of color to a blanched nailbed' and was limited to Emergency Department and Intensive Care Unit settings. Our search used OVID Medline from 1946 through December of 2022 and resulted in 800 articles that led to 13 being included in the final analysis. Included studies were appraised using the Newcastle Ottawa Score.

Overall, the strength of the evidence across the 13 final studies was moderate. Studies suffered from numerous methodological shortcomings, and reproducibility in how they measured capillary refill.

Capillary refill has the potential to assist in the assessment of circulatory dysfunction in sepsis; however, emerging technologies making bedside measurement more reproducible and reliable must be further developed and studied in prospective randomized control trials powered to predict meaningful patient outcomes.

 Peripheral perfusion monitoring is crucial for the management of critically ill patients because abnormal peripheral perfusion is associated with a poor prognosis. The peripheral perfusion index (PPI), derived from pulse oximetry, quantifies peripheral perfusion but varies across fingers. A pulse oximeter probe may cause burns when worn at the same site. Therefore, changing the site has been recommended. However, changes in PPI values owing to probe replacement reduce the reliability of clinical and research applications. No two fingers with equivalent PPI values have been identified yet. This study assessed the interfinger differences in PPI by measuring the five fingers simultaneously and identified the two fingers with the least fluctuation in values.

 A total of 30 healthy volunteers were included in this single-center prospective exploratory study. For PPI measurements, the pulse amplitude index (PAI) was measured using a pulse oximeter on a bedside monitor (Life Scope PT; Nihon Kohden Corp., Tokyo, Japan). The tape-type disposable pulse oximeter probes were attached to each of the five fingertips of the dominant hand, and measurements were conducted in three rooms with different temperatures (16°C, 22°C, and 28°C) to induce thermoregulatory responses and capture a wide range of PAI values. The primary endpoint was the PAI in pairs of two fingers each (a total of 10 pairs). Paired t-tests with Bonferroni correction were used to compare finger pairs, with statistical significance defined as p < 0.005.

The combination with the least difference in PAI was the index-ring finger combination (0.07% ± 1.89%, p = 0.74), followed by the middle-ring finger (0.45% ± 1.93%, p = 0.03) and index-middle finger combinations (0.52% ± 2.05%, p = 0.02). All other finger combinations showed statistically significant differences (p < 0.001).

 PPI values measured using the pulse oximeter showed the smallest interfinger difference between the index and ring fingers. If changing the finger to which the probe is attached during clinical or research use is needed, it may be possible to consistently measure the PPI values by alternately attaching the probe to the index and ring fingers.

Nutritional support and optimal glucose control are key components of care during critical illness, yet evidence surrounding their use remains conflicting, making translation into clinical practice challenging. This review explores Bayesian methods to enhance the interpretation of frequentist critical care trials, particularly for interventions with inconclusive outcomes.

Bayesian re-analysis frameworks may clarify conflicting evidence in critical care, thus enhancing interpretability and supporting clinical decision-making. This review focuses on the Bayesian re-analysis of three recent trials with indeterminate results for mortality - NUTRIREA-3, EFFORT Protein, and TGC-Fast - that examined the effects of enteral nutrition and glucose control strategies.

We re-analyzed the mortality outcomes of these trials within a Bayesian framework, contrasting our findings with the original trial results to illustrate how Bayesian methods can enhance the clinical applicability of trial outcomes. Although Bayesian and frequentist analyses generally agree on the direction and magnitude of effect, Bayesian methods offer the advantage of providing posterior probabilities of benefit and harm, thus identifying promising and potentially harmful interventions. This review underscores the value of Bayesian analysis in re-evaluating clinical trial data and guiding clinical practice.

(1) Background: To develop a novel capillary refill time measurement system and evaluate its reliability and reproducibility. (2) Methods: Firstly, the utilization of electromagnetic pressure technology facilitates the automatic compression and instantaneous release of the finger. Secondly, the employment of pressure sensing technology and photoelectric volumetric pulse wave analysis technology enables the dynamic monitoring of blood flow in distal tissues. Thirdly, the subjects were recruited to compare the average measurement time and the number of measurements required for successful measurements. The satisfaction of doctors and patients with the instrument was investigated through the administration of questionnaires. Finally, 71 subjects were recruited and divided into two groups, A and B. Three doctors repeated the measurement of the right index fingers of the subjects. In Group A, the same measuring instrument was used, and the consistency of the measurements was evaluated using the intragroup correlation coefficient. In Group B, one doctor repeated the measurement of each subject three times using the same measuring instrument, and the reproducibility of the CRT was evaluated using the analysis of variance of the repeated measurement data. (3) Results: The development of the capillary refill time meter was successful, with an average measurement time of 18 s and a single measurement. This study found that doctor-patient satisfaction levels were 98.3% and 100%, respectively. The intraclass correlation coefficient was 0.995 in Group A, and the p-value was greater than 0.05 in Group B. (4) Conclusions: The non-invasive monitoring of microcirculation has been rendered both rapid and effective, thus paving the way for the further mechanization and standardization of this process. The CRT, when measured using the capillary refill time meter test machine, demonstrated consistent and reproducible results, both when assessed by different researchers and when evaluated across varying measurement sets.

The influence of high positive end-expiratory pressure (PEEP) with recruitment maneuvers on the occurrence of postoperative pulmonary complications after surgery is still not definitively established. Bayesian analysis can help to gain further insights from the available data and provide a probabilistic framework that is easier to interpret. The objective was to estimate the posterior probability that the use of high PEEP with recruitment maneuvers is associated with reduced postoperative pulmonary complications in patients with intermediate-to-high risk under neutral, pessimistic, and optimistic expectations regarding the treatment effect.

Multilevel Bayesian logistic regression analysis was performed on individual patient data from three randomized clinical trials carried out on surgical patients at intermediate to high risk for postoperative pulmonary complications. The main outcome was the occurrence of postoperative pulmonary complications in the early postoperative period. This study examined the effect of high PEEP with recruitment maneuvers versus low PEEP ventilation. Priors were chosen to reflect neutral, pessimistic, and optimistic expectations of the treatment effect.

Using a neutral, pessimistic, or optimistic prior, the posterior mean odds ratio for high PEEP with recruitment maneuvers compared to low PEEP was 0.85 (95% credible interval, 0.71 to 1.02), 0.87 (0.72 to 1.04), and 0.86 (0.71 to 1.02), respectively. Regardless of prior beliefs, the posterior probability of experiencing a beneficial effect exceeded 90%. Subgroup analysis indicated a more pronounced effect in patients who underwent laparoscopy (odds ratio, 0.67 [0.50 to 0.87]) and those at high risk for postoperative pulmonary complications (odds ratio, 0.80 [0.53 to 1.13]). Sensitivity analysis, considering severe postoperative pulmonary complications only or applying a different heterogeneity prior, yielded consistent results.

High PEEP with recruitment maneuvers demonstrated a moderate reduction in the probability of postoperative pulmonary complication occurrence, with a high posterior probability of benefit observed consistently across various prior beliefs, particularly among patients who underwent laparoscopy.

To generate consensus and provide expert clinical practice statements for the management of adult sepsis in resource-limited settings.

An international multidisciplinary Steering Committee with expertise in sepsis management and including a Delphi methodologist was convened by the Asia Pacific Sepsis Alliance (APSA). The committee selected an international panel of clinicians and researchers with expertise in sepsis management. A Delphi process based on an iterative approach was used to obtain the final consensus statements.

A stable consensus was achieved for 30 (94%) of the statements by 41 experts after four survey rounds. These include consensus on managing patients with sepsis outside a designated critical care area, triggers for escalating clinical management and criteria for safe transfer to another facility. The experts agreed on the following: in the absence of serum lactate, clinical parameters such as altered mental status, capillary refill time and urine output may be used to guide resuscitation; special considerations regarding the volume of fluid used for resuscitation, especially in tropical infections, including the use of simple tests to assess fluid responsiveness when facilities for advanced hemodynamic monitoring are limited; use of Ringer's lactate or Hartmann's solution as balanced salt solutions; epinephrine when norepinephrine or vasopressin are unavailable; and the administration of vasopressors via a peripheral vein if central venous access is unavailable or not feasible. Similarly, where facilities for investigation are unavailable, there was consensus for empirical antimicrobial administration without delay when sepsis was strongly suspected, as was the empirical use of antiparasitic agents in patients with suspicion of parasitic infections.

Using a Delphi method, international experts reached consensus to generate expert clinical practice statements providing guidance to clinicians worldwide on the management of sepsis in resource-limited settings. These statements complement existing guidelines where evidence is lacking and add relevant aspects of sepsis management that are not addressed by current international guidelines. Future studies are needed to assess the effects of these practice statements and address remaining uncertainties.

The timing of coronary angiography in patients with successfully resuscitated out-of-hospital cardiac arrest and missing ST-segment elevations on the electrocardiogram has been investigated in 2 large randomized controlled trials, TOMAHAWK (Angiography After Out-of-Hospital Cardiac Arrest Without ST-Segment Elevation) and COACT (Coronary Angiography After Cardiac Arrest Trial). Both trials found neutral results for immediate vs delayed/selective coronary angiography on short-term all-cause mortality. The TOMAHAWK trial showed a tendency towards harm with immediate coronary angiography, though not statistically significant with traditional frequentist methods. Probabilistic analyses of both trials may enable greater clinical understanding of the trial findings.

The purpose of this study was to perform reanalyses of both trials within a Bayesian framework.

Post hoc analyses of both multicenter randomized controlled trials were performed in both cohorts separately and combined. The primary endpoint, 30-day all-cause mortality, was analyzed using Bayesian logistic regression. A spectrum of priors included "flat," "neutral," "optimistic," and "pessimistic" priors based on assumptions made when designing both trials.

In the TOMAHAWK trial, immediate coronary angiography showed a very high posterior probability of increased mortality between 90% and 97% across all priors. The ORs across all priors were directed towards harm. Similarly, COACT showed odds ratios ranging from 0.98 to 1.11 for the 30-day mortality endpoint. When combining both trials, immediate coronary angiography showed a high probability of increased mortality between 83% and 95%, again with ORs across all priors indicating a direction towards harm.

Bayesian reanalyses showed a very high probability of increased 30-day mortality risk with immediate compared with delayed/selective coronary angiography in the TOMAHAWK trial and combined trial cohort. These findings may shift the current understanding of both trials from a "neutral" towards a likely "harmful" effect of immediate coronary angiography after successfully resuscitated out-of-hospital cardiac arrest without ST-segment elevations. Therefore, adoption of a delayed strategy of coronary angiography might be preferred in clinical practice until the results of the DISCO (Direct or Subacute Coronary Angiography in Out-of-Hospital Cardiac Arrest) trial become available.

The objective of this review is to provide a comprehensive management protocol for the treatment of intracranial pressure (ICP) crises based on the latest evidence.

The review discusses updated information on various aspects of critical care management in patients experiencing ICP crises, including mechanical ventilation, fluid therapy, hemoglobin targets, and hypertonic saline infusion, the advantages of ICP monitoring, the critical ICP threshold, and bedside neuromonitoring. All aspects of critical care treatment, including hemodynamic and respiratory support and adjustment of ICP reduction therapy, may impact patient outcomes. ICP monitoring allows ICP values, trends, waveforms, and CPP calculation, which are helpful to guide patient care. Advanced neuromonitoring devices are available at the bedside to diagnose impaired intracranial compliance and intracranial hypertension, assess brain function, and optimize cerebral perfusion. Future research should focus on developing appropriate intervention protocols for both invasive and noninvasive neuromonitoring in managing ICP crisis patients.

The monitoring of peripheral circulation, as indicated by the capillary refill time, is a sensitive and accurate method of assessing the microcirculatory status of the body. It is a widely used tool for the evaluation of critically ill patients, the guidance of therapeutic interventions, and the assessment of prognosis. In recent years, there has been a growing emphasis on microcirculation monitoring which has led to an increased focus on capillary refill time. The International Sepsis Guidelines, the American Academy of Pediatrics, the World Health Organization, and the American Heart Association all recommend its inclusion in the evaluation of the system in question. Furthermore, the methodology for its measurement has evolved from a traditional manual approach to semiautomatic and fully automatic techniques. This article presents a comprehensive overview of the current research on the measurement of capillary refill time, with a particular focus on its clinical significance. The aim is to provide a valuable reference for clinicians and researchers and further advance the development and application of microcirculation monitoring technology.

This editorial aims to highlight the evolving concept of protective hemodynamics in the management of critically ill patients.

Recent literature underscores the limitations of rigid blood pressure targets, particularly in the context of critical care and perioperative management. High blood pressure targets, especially when coupled with high-dose vasopressors, can lead to poor outcomes. 'Protective hemodynamics' aims to maintain cardiovascular stability while reducing risks associated with interventions.

The implications of adopting protective hemodynamics are profound for both clinical practice and research. Clinically, this approach can reduce iatrogenic harm and improve long-term outcomes for critically ill patients. For research, it opens new avenues for investigating individualized hemodynamic management strategies that prioritize overall patient stability and long-term health over rigid target attainment.

Continuous, noninvasive tools to monitor peripheral perfusion, such as perfusion index (PI), can detect hemodynamic abnormalities and assist in the management of critically ill children hospitalized with severe malaria. In this study of hospitalized children with severe malaria, we aimed to assess whether PI correlates with clinical markers of perfusion and to determine whether combining PI with these clinical measures improves identification of children with greater odds of mortality.

Post hoc analysis of a prospective, multicenter, cohort study conducted between 2014 and 2017.

Two referral hospitals in Central and Eastern Uganda.

Six hundred children younger than 5 years old with severe malaria and 120 asymptomatic community children.

None.

PI was measured at 6-hour intervals for the first 24 hours of hospitalization. We compared PI to standard clinical perfusion measures such as capillary refill time, presence of cold peripheral limbs, or temperature gradient. Admission PI was highly correlated with clinical measures of perfusion. Admission PI was lower in children with severe malaria compared with asymptomatic community children; and, among the children with severe malaria, PI was lower in those with clinical features of poor perfusion or complications of severe malaria, such as shock and hyperlactatemia (all p < 0.02). Among children with severe malaria, lower admission PI was associated with greater odds of mortality after adjustment for age, sex, and severe malaria criteria (adjusted odds ratio, 2.4 for each log decrease in PI [95% CI, 1.0-5.9]; p = 0.045). Diagnostically, the presence of two consecutive low PI measures (< 1%) predicted mortality, with a sensitivity of 50% and a specificity of 76%.

In severe malaria, PI correlates with clinical complications (including shock and elevated serum lactate) and may be useful as an objective, continuous explanatory variable associated with greater odds of later in-hospital mortality.

The most used vasopressors in critically ill patients are exogenous catecholamines, mainly norepinephrine. Their use can be associated with serious adverse events and even increased mortality, especially if administered at high doses. In recent years, the addition of vasopressin has been proposed to counteract the deleterious effects of high doses of catecholamines (decatecholaminization) with the intention of improving the prognosis of these patients. Currently, vasopressin has two main indications: septic shock and vasoplegic shock in the postoperative period of cardiac surgery. In septic shock, current evidence favors its early initiation before reaching high doses of norepinephrine. In the postoperative period of cardiac surgery, the different benefits of the use of vasopressin have been studied, especially in patients with atrial fibrillation and pulmonary hypertension. When used properly, vasopressin is a safe an effective drug for the indications described above.

The ROSE concept, which is the acronym of resuscitation, optimization, stabilization and evacuation, describes the phases of fluid therapy, based on the pathophysiology of septic shock. During the first two phases, aggressive fluid therapy that is guided by clinical and hemodynamic parameters is mandatory. During the stabilization phase, recovery from shock and microcirculatory injury occurs, which enables the depletion of fluid overload in the fourth and final phase. Ultimately, euvolemia needs to be regained, which reverts interstitial edema and organ dysfunction.

Background: The peripheral perfusion index (PI) reflects microcirculatory blood flow perfusion and indicates the severity and prognosis of sepsis. Method: The cohort comprised 208 patients admitted to the intensive care unit (ICU) with infection, among which 117 had sepsis. Demographics, medication history, ICU variables, and laboratory indexes were collected. Primary endpoints were in-hospital mortality and 28-day mortality. Secondary endpoints included organ function variables (coagulation function, liver function, renal function, and myocardial injury), lactate concentration, mechanical ventilation time, and length of ICU stay. Univariate and multivariate analyses were conducted to assess the associations between the PI and clinical outcomes. Sensitivity analyses were performed to explore the associations between the PI and organ functions in the sepsis and nonsepsis groups. Result: The PI was negatively associated with in-hospital mortality (odds ratio [OR] 0.29, 95% confidence interval [CI] 0.15 to 0.55), but was not associated with 28-day mortality. The PI was negatively associated with the coagulation markers prothrombin time (PT) (β -0.36, 95% CI -0.59 to 0.13) and activated partial thromboplastin time (APTT) (β -1.08, 95% CI -1.86 to 0.31), and the myocardial injury marker cardiac troponin I (cTnI) (β -2085.48, 95% CI -3892.35 to 278.61) in univariate analysis, and with the PT (β -0.36, 95% CI -0.60 to 0.13) in multivariate analysis. The PI was negatively associated with the lactate concentration (β -0.57, 95% CI -0.95 to 0.19), mechanical ventilation time (β -23.11, 95% CI -36.54 to 9.69), and length of ICU stay (β -1.28, 95% CI -2.01 to 0.55). Sensitivity analyses showed that the PI was significantly associated with coagulation markers (PT and APTT) and a myocardial injury marker (cTnI) in patients with sepsis, suggesting that the associations between the PI and organ function were stronger in the sepsis group than the nonsepsis group. Conclusion: The PI provides new insights for assessing the disease severity, short-term prognosis, and organ function damage in ICU patients with sepsis, laying a theoretical foundation for future research.

Adequately powered randomized controlled trials (RCTs) are considered the highest level of evidence in guiding clinical practice. Reports using Bayesian hypothesis-testing to reanalyze RCTs are increasing. One distinct advantage of Bayesian analysis is that we can obtain a range of numerical probabilities that reflect how likely a study intervention is more effective than the alternative after considering both pre-existing available evidence and the alternate hypotheses. A recent analysis of critical care trials showed that some trials with an indeterminate result according to the frequentist analysis could have a high probability of being effective when reinterpreted by Bayesian analysis. In this perspective article, we will discuss the caveats in interpreting the results of Bayesian reanalysis of RCTs before we change clinical practice. When overoptimistic hypothesis prior probabilities are used, it carries a risk to translate noises into false signals. Using Bayes factors (BFs) to quantify evidence contained in data (by the ratio of the probability of data under each hypothesis) is thus more preferable than using a single prior probability, such that the BF approach becomes the mainstream in Bayesian hypothesis-testing. Still, BFs are dependent on the prior parameter distributions; comparing different hypotheses would invariably result in different results.

Ho KM, Lee A. Using Bayesian Hypothesis-testing to Reanalyze Randomized Controlled Trials: Does it Always Tell the Truth, the Whole Truth and Nothing but the Truth? Indian J Crit Care Med 2024;28(11):1005-1008.

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.

To give physicians a concise overview of CRT and explore recent evidence on its reliability and value in the management of sepsis.

A narrative review.

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.

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.

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.

Septic shock is a frequent critical clinical condition and a leading cause of death in critically ill individuals. However, it is challenging to identify affected patients early. In this article, we discuss new perspectives on the methods and uses of peripheral perfusion monitoring, considering the concept of a dysregulated response. Physical examination, and visual and ultrasonographic techniques are used to measure peripheral microcirculatory blood flow to reflect tissue perfusion. Compared with other monitoring techniques, peripheral perfusion monitoring has the benefits of low invasiveness and good repeatability, and allows for quick therapeutic judgments, which have significant practical relevance. Peripheral perfusion monitoring is an effective tool to detect early signs of septic shock, autonomic dysfunction, and organ damage. This method can also be used to evaluate treatment effectiveness, direct fluid resuscitation and the use of vasoactive medications, and monitor vascular reactivity, microcirculatory disorders, and endothelial cell damage. Recent introductions of novel peripheral perfusion monitoring methods, new knowledge of peripheral perfusion kinetics, and multimodal peripheral perfusion evaluation methods have occurred. To investigate new knowledge and therapeutic implications, we examined the methodological attributes and mechanisms of peripheral perfusion monitoring, in this study.

Background/Objectives: In critically ill patients, achieving a mean arterial pressure (MAP) of 65 mmHg is a recommended resuscitation goal to ensure proper tissue oxygenation. Unfortunately, some patients do not benefit from providing such a value, suggesting that other indices are needed for better hemodynamic assessment. Capillary refill time (CRT) has emerged as an established marker for peripheral perfusion and a therapeutic target in critical illness, but its relationship with other exponents of hypoperfusion during vasopressor support after resuscitation period still warrants further research. This study aimed to investigate whether in critically ill patients after initial resuscitation, CRT would provide information independent of other, readily accessible hemodynamic variables. Methods: Critically ill patients who were mechanically ventilated after the resuscitation period and receiving vasopressors were prospectively studied between December 2022 and June 2023. Vasopressor support was measured using norepinephrine equivalent doses (NEDs). CRT, MAP and NED were assessed simultaneously and analyzed using Spearman's rank correlation. Results: A total of 92 patients were included and 210 combined MAP-CRT-NED-Lactate records were obtained. There was no correlation between CRT and MAP (R = -0.1, p = 0.14) or lactate (R = 0.11, p = 0.13), but there was a positive weak correlation between CRT and NED (R = 0.25, p = 0.0005). In patients with hypotension, in 83% of cases (15/18), CRT was within normal range, despite different doses of catecholamines. When assessing patients with high catecholamine doses, in 58% cases (11/19), CRT was normal and MAP was usually above 65 mmHg. Conclusions: Capillary refill time provides additional hemodynamic information that is not highly related with the values of mean arterial pressure, lactate level and vasopressor doses. It could be incorporated into routine physical examination in critically ill patients who are beyond initial resuscitation.

To familiarize clinicians with the emerging concepts in critical care research of Bayesian thinking and personalized medicine through phenotyping and explain their clinical relevance by highlighting how they address the issues of frequent negative trials and heterogeneity of treatment effect.

The past decades have seen many negative (effect-neutral) critical care trials of promising interventions, culminating in calls to improve the field's research through adopting Bayesian thinking and increasing personalization of critical care medicine through phenotyping. Bayesian analyses add interpretive power for clinicians as they summarize treatment effects based on probabilities of benefit or harm, contrasting with conventional frequentist statistics that either affirm or reject a null hypothesis. Critical care trials are beginning to include prospective Bayesian analyses, and many trials have undergone reanalysis with Bayesian methods. Phenotyping seeks to identify treatable traits to target interventions to patients expected to derive benefit. Phenotyping and subphenotyping have gained prominence in the most syndromic and heterogenous critical care disease states, acute respiratory distress syndrome and sepsis. Grouping of patients has been informative across a spectrum of clinically observable physiological parameters, biomarkers, and genomic data. Bayesian thinking and phenotyping are emerging as elements of adaptive clinical trials and predictive enrichment, paving the way for a new era of high-quality evidence. These concepts share a common goal, sifting through the noise of heterogeneity in critical care to increase the value of existing and future research.

The future of critical care medicine will inevitably involve modification of statistical methods through Bayesian analyses and targeted therapeutics via phenotyping. Clinicians must be familiar with these systems that support recommendations to improve decision-making in the gray areas of critical care practice.

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.

Early shock reversal is crucial to improve patient outcomes. Capillary refill time (CRT) is clinically important to identify and monitor shock in children but has issues with inconsistency. To minimize inconsistency, we evaluated a CRT monitoring system using an automated compression device. Our objective was to determine proper compression pressure in children.

Clinician force for CRT was collected during manual CRT measurement as a reference for automated compression in a previous study (12.9 N, 95% confidence interval, 12.5-13.4; n = 454). An automated compression device with a soft inflation bladder was fitted with a force sensor. We evaluated the effectiveness of the automated pressure to eliminate pulsatile blood flow from the distal phalange. Median and variance of CRT analysis at each pressure was compared.

A comparison of pressures at 300 to 500 mm Hg on a simulated finger yielded a force of 5 to 10 N, and these pressures were subsequently used for automated compression for CRT. Automated compression was tested in 44 subjects (median age, 33 months; interquartile range [IQR], 14-56 months). At interim analysis of 17 subjects, there was significant difference in the waveform with residual pulsatile blood flow (9/50: 18% at 300 mm Hg, 5/50:10% at 400 mm Hg, 0/51: 0% at 500 mm Hg, P = 0.008). With subsequent enrollment of 27 subjects at 400 and 500 mm Hg, none had residual pulsatile blood flow. There was no difference in the CRT: median 1.8 (IQR, 1.06-2.875) in 400 mm Hg vs median 1.87 (IQR, 1.25-2.8325) in 500 mm Hg, P = 0.81. The variance of CRT was significantly larger in 400 mm Hg: 2.99 in 400 mm Hg vs. 1.35 in 500 mm Hg, P = 0.02, Levene's test. Intraclass correlation coefficient for automated CRT was 0.56 at 400 mm Hg and 0.78 at 500 mm Hg.

Using clinician CRT measurement data, we determined either 400 or 500 mm Hg is an appropriate pressure for automated CRT, although 500 mm Hg demonstrates superior consistency.

Acute circulatory shock is a life-threatening emergency requiring an efficient and timely management plan, which varies according to shock etiology and pathophysiology. Specific guidelines have been developed for each type of shock; however, there is a need for a clear timeline to promptly implement initial life-saving interventions during the early phase of shock recognition and management. A simple, easily memorable bundle of interventions could facilitate standardized management with clear targets and specified timeline. The authors propose the "MINUTES" acronym which summarizes essential interventions which should be performed within the first 30 min following shock recognition. All the interventions in the MINUTES bundle are suitable for any patient with undifferentiated shock. In addition to the acronym, we suggest a timeline for each step, balancing the feasibility and urgency of each intervention. The MINUTES acronym includes seven sequential steps which should be performed in the first 30 min following shock recognition: Maintain "ABCs", INfuse vasopressors and/or fluids (to support hemodynamic/perfusion) and INvestigate with simple blood tests, Ultrasound to detect the type of shock, Treat the underlying Etiology, and Stabilize organ perfusion.

Tissue hypoxia is associated with the development of organ dysfunction and death in critically ill patients commonly captured using blood lactate. The kinetic parameters of serial lactate evaluations are superior at predicting mortality compared with single values. S-adenosylhomocysteine (SAH), which is also associated with hypoxia, was recently established as a useful predictor of septic organ dysfunction and death. We evaluated the performance of kinetic SAH parameters for mortality prediction compared with lactate parameters in a cohort of critically ill patients. For lactate and SAH, maxima and means as well as the normalized area scores were calculated for two periods: the first 24 h and the total study period of up to five days following ICU admission. Their performance in predicting in-hospital mortality were compared in 99 patients. All evaluated parameters of lactate and SAH were significantly higher in non-survivors compared with survivors. In univariate analysis, the predictive power for mortality of SAH was higher compared with lactate in all forms of application. Multivariable models containing SAH parameters demonstrated higher predictive values for mortality than models based on lactate parameters. The optimal models for mortality prediction incorporated both lactate and SAH parameters. Compared with lactate, SAH displayed stronger predictive power for mortality in static and dynamic application in critically ill patients.

This review summarizes current literature about the relationships between macro and microcirculation and their practical clinical implications in children with septic shock.

Current evidence from experimental and clinical observational studies in children and adults with septic shock reveals that the response to treatment and resuscitation is widely variable. Furthermore, there is a loss of hemodynamic coherence, as resuscitation-induced improvement in macrocirculation (systemic hemodynamic parameters) does not necessarily result in a parallel improvement in the microcirculation. Therefore, patient-tailored monitoring is essential in order to adjust treatment requirements during resuscitation in septic shock. Optimal monitoring must integrate macrocirculation (heart rate, blood pressure, cardiac output, and ultrasound images), microcirculation (videomicroscopy parameters and capillary refill time) and cellular metabolism (lactic acid, central venous blood oxygen saturation, and difference of central venous to arterial carbon dioxide partial pressure).

There is a dire need for high-quality studies to assess the relationships between macrocirculation, microcirculation and tissue metabolism in children with septic shock. The development of reliable and readily available microcirculation and tissue perfusion biomarkers (other than lactic acid) is also necessary to improve monitoring and treatment adjustment in such patients.

Data from the Neonatal Oxygenation Prospective Meta-analysis (NeOProM) indicate that targeting a higher (91-95%) versus lower (85-89%) pulse oximeter saturation (SpO2) range may reduce mortality and necrotizing enterocolitis (NEC) and increase retinopathy of prematurity (ROP). Aiming to re-evaluate the strength of this evidence, we conducted a Bayesian reanalysis of the NeOProM data. We used Bayes factors (BFs) to evaluate the likelihood of the data under the combination of models assuming the presence vs. absence of effect, heterogeneity, and moderation by sex. The Bayesian reanalysis showed moderate evidence in favor of no differences between SpO2 targets (BF10 = 0.30) in death or major disability, but moderate evidence (BF10 = 3.60) in favor of a lower mortality in the higher SpO2 group. Evidence in favor of differences was observed for bronchopulmonary dysplasia (BPD) (BF10 = 14.44, lower rate with lower SpO2), severe NEC (BF10 = 9.94), and treated ROP (BF10 = 3.36). The only outcome with moderate evidence in favor of sex differences was BPD. This reanalysis of the NeOProM trials confirmed that exposure to a lower versus higher SpO2 range is associated with a higher mortality and risk of NEC, but a lower risk of ROP and BPD. The Bayesian approach can help in assessing the strength of evidence supporting clinical decisions.

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.

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).

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.

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.

To provide consensus recommendations regarding hemodynamic data reporting in studies investigating fluid responsiveness and fluid challenge (FC) use in the intensive care unit (ICU).

The Executive Committee of the European Society of Intensive Care Medicine (ESICM) commissioned and supervised the project. A panel of 18 international experts and a methodologist identified main domains and items from a systematic literature, plus 2 ancillary domains. A three-step Delphi process based on an iterative approach was used to obtain the final consensus. In the Delphi 1 and 2, the items were selected with strong (≥ 80% of votes) or week agreement (70-80% of votes), while the Delphi 3 generated recommended (≥ 90% of votes) or suggested (80-90% of votes) items (RI and SI, respectively).

We identified 5 main domains initially including 117 items and the consensus finally resulted in 52 recommendations or suggestions: 18 RIs and 2 SIs statements were obtained for the domain "ICU admission", 11 RIs and 1 SI for the domain "mechanical ventilation", 5 RIs for the domain "reason for giving a FC", 8 RIs for the domain pre- and post-FC "hemodynamic data", and 7 RIs for the domain "pre-FC infused drugs". We had no consensus on the use of echocardiography, strong agreement regarding the volume (4 ml/kg) and the reference variable (cardiac output), while weak on administration rate (within 10 min) of FC in this setting.

This consensus found 5 main domains and provided 52 recommendations for data reporting in studies investigating fluid responsiveness in ICU patients.

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.

To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock.

Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities.

Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article.

A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis?

Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.

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.

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.

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.

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.

To determine the diagnostic performance of the clinical evaluation of peripheral tissue perfusion in the prediction of mortality.

Systematic review and meta-analysis.

Intensive care unit.

Patients with sepsis and septic shock.

Studies of patients with sepsis and/or septic shock that associated clinical monitoring of tissue perfusion with mortality were included. A systematic review was performed by searching the PubMed/MEDLINE, Cochrane Library, SCOPUS, and OVID databases.

The risk of bias was assessed with the QUADAS-2 tool. Sensitivity and specificity were calculated to evaluate the predictive accuracy for mortality. Review Manager software version 5.4 was used to draw the forest plot graphs, and Stata version 15.1 was used to build the hierarchical summary receiver operating characteristic model.

Thirteen studies were included, with a total of 1667 patients and 17 analyses. Two articles evaluated the temperature gradient, four evaluated the capillary refill time, and seven evaluated the mottling in the skin. In most studies, the outcome was mortality at 14 or 28 days. The pooled sensitivity of the included studies was 70%, specificity 75.9% (95% CI, 61.6%-86.2%), diagnostic odds ratio 7.41 (95% CI, 3.91-14.04), and positive and negative likelihood ratios 2.91 (95% CI, 1.80-4.72) and 0.39 (95% CI, 0.30-0.51), respectively.

Clinical evaluation of tissue perfusion at the bedside is a useful tool, with moderate sensitivity and specificity, to identify patients with a higher risk of death among those with sepsis and septic shock.

PROSPERO CRD42019134351.

To investigate whether a Bayesian interpretation might help prevent misinterpretation of statistical findings and support authors to differentiate evidence of no effect from statistical uncertainty.

A Bayesian re-analysis to determine posterior probabilities of clinically important effects (e.g., a large effect is set at a 4 percentage point difference and a trivial effect to be within a 0.5 percentage point difference). Posterior probabilities greater than 95% are considered as strong statistical evidence, and less than 95% as inconclusive.

150 major women's health trials with binary outcomes.

Posterior probabilities of large, moderate, small and trivial effects.

Under frequentist methods, 48 (32%) were statistically significant (p-value ≤ 0.05) and 102 (68%) statistically non-significant. The frequentist and Bayesian point estimates and confidence intervals showed strong concordance. Of the statistically non-significant trials (n = 102), the Bayesian approach classified the majority (94, 92%) as inconclusive, neither able to confirm or refute effectiveness. A small number of statistically non-significant findings (8, 8%) were classified as having strong statistical evidence of an effect.

Whilst almost all trials report confidence intervals, in practice most statistical findings are interpreted on the basis of statistical significance, mostly concluding evidence of no effect. Findings here suggest the majority are likely uncertain. A Bayesian approach could help differentiate evidence of no effect from statistical uncertainty.

It is unclear how often survival benefits observed in single-center randomized controlled trials (sRCTs) involving critically ill patients are confirmed by subsequent multicenter randomized controlled trials (mRCTs). We aimed to perform a systemic literature review of sRCTs with a statistically significant mortality reduction and to evaluate whether subsequent mRCTs confirmed such reduction.

We searched PubMed for sRCTs published in the New England Journal of Medicine, JAMA, or Lancet, from inception until December 31, 2016. We selected studies reporting a statistically significant mortality decrease using any intervention (drug, technique, or strategy) in adult critically ill patients. We then searched for subsequent mRCTs addressing the same research question tested by the sRCT. We compared the concordance of results between sRCTs and mRCTs when any mRCT was available. We registered this systematic review in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023455362).

We identified 19 sRCTs reporting a significant mortality reduction in adult critically ill patients. For 16 sRCTs, we identified at least one subsequent mRCT (24 trials in total), while the interventions from three sRCTs have not yet been addressed in a subsequent mRCT. Only one out of 16 sRCTs (6%) was followed by a mRCT replicating a significant mortality reduction; 14 (88%) were followed by mRCTs with no mortality difference. The positive finding of one sRCT (6%) on intensive glycemic control was contradicted by a subsequent mRCT showing a significant mortality increase. Of the 14 sRCTs referenced at least once in international guidelines, six (43%) have since been either removed or suggested against in the most recent versions of relevant guidelines.

Mortality reduction shown by sRCTs is typically not replicated by mRCTs. The findings of sRCTs should be considered hypothesis-generating and should not contribute to guidelines.

Bayesian analysis of randomized controlled trials (RCTs) can extend the value of trial data beyond interpretations based on conventional p value-based binary cutoffs. We conducted an exploratory post hoc Bayesian reanalysis of the minimally invasive surgery with thrombolysis for intracerebral hemorrhage (ICH) evacuation (MISTIE-3) trial and derived probabilities of potential intervention effect on functional and survival outcomes.

MISTIE-3 was a multicenter phase 3 RCT designed to evaluate the efficacy and safety of the MISTIE intervention. Five hundred and six adults (18 years or older) with spontaneous, nontraumatic, supratentorial ICH of ≥30 mL were randomized to receive either the MISTIE intervention (n = 255) or standard medical care (n = 251). We provide Bayesian-derived estimates of the effect of the MISTIE intervention on achieving a good 365-day modified Rankin Scale score (mRS score 0-3) as relative risk (RR) and absolute risk difference (ARD), and the probabilities that these treatment effects are greater than prespecified thresholds. We used 2 sets of prior distributions: (1) reference priors, including minimally informative, enthusiastic, and skeptical priors, and (2) data-derived prior distribution, using a hierarchical random effects model. We additionally evaluated the potential effects of the MISTIE intervention on 180-day and 30-day mRS and 365-, 180-, and 30-day mortality using data-derived priors.

The Bayesian-derived probability that MISTIE intervention has any beneficial effect (RR >1) on achieving a good 365-day mRS score was 70% using minimally informative prior, 87% with enthusiastic prior, 68% with skeptical prior, and 73% with data-derived prior. However, these probabilities were ≤55% for RR >1.10 and 0% for RR >1.52 across a range of priors. The probabilities of achieving RR >1 for 180- and 30-day mRS scores are 65% and 80%, respectively. Furthermore, the probabilities of achieving RR <1 for 365-, 180-, and 30-day mortality are 93%, 98%, and 99%, respectively.

Our exploratory analyses indicate that across a range of priors, the Bayesian-derived probability of MISTIE intervention having any beneficial effect on 365-day mRS for patients with ICH is between 68% and 87%. These analyses do not change the frequentist-based interpretation of the trial. However, unlike the frequentist p values, which indirectly evaluate treatment effects and only provide an arbitrary binary cutoff (such as 0.05), the Bayesian framework directly estimates the probabilities of potential treatment effects.

ClinicalTrials.gov/ct2/show/NCT01827046.

This study provides Class II evidence that minimally invasive surgery (MIS) + recombinant tissue plasminogen activator (rt-PA) does not significantly improve functional outcome in patients with ICH. However, this study lacks the precision to exclude a potential benefit of MIS + rt-PA.