Discordance Between Capillary Refill Time and Oxygen Extraction Ratio in Septic Shock (DISCO-SHOCK)

Discordance Between Capillary Refill Time and Oxygen Extraction Ratio in Septic Shock: A Prospective Observational Cohort Study Evaluating Its Prevalence and Prognostic Value

In septic shock, restoring large-vessel (macrocirculatory) perfusion-reflected by a normal capillary refill time (CRT)-does not always mean that oxygen use at the tissue level has recovered. This mismatch, sometimes called loss of hemodynamic coherence, may be detectable by comparing CRT with the oxygen extraction ratio (O₂ER), a marker of how much oxygen the tissues are extracting from the blood. Patients whose CRT has normalized but whose O₂ER remains abnormal-either too high (suggesting oxygen delivery that is insufficient for demand) or too low (suggesting microcirculatory shunting)-are considered to have a "discordant" perfusion phenotype.

This prospective, single-center, observational cohort study aims to determine how often this CRT-O₂ER discordance occurs at the 6th hour of resuscitation in adult patients with septic shock, and whether it is associated with 28-day mortality. Approximately 100 consecutive adult patients diagnosed with septic shock (with pre-existing central venous and arterial catheters) will be followed. Clinical and laboratory measurements-including CRT, O₂ER, lactate, mottling score, and organ dysfunction scores-will be recorded at hours 0, 6, 12, and 24, with the main phenotype grouping performed at hour 6. The study is purely observational: CRT is a painless, non-invasive bedside measurement, and O₂ER is calculated from blood gas samples already drawn as part of routine care, so no additional interventions or blood draws are performed for research purposes.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Diagnostic test: Capillary refill time (CRT); Diagnostic test: Oxygen extraction ratio (O₂ER) assessment

Detailed Description

Background. In septic shock resuscitation, improvement of macrocirculatory targets such as blood pressure and capillary refill time (CRT) does not always reflect adequate oxygen utilization at the tissue level-a phenomenon described as loss of hemodynamic coherence. Although the ANDROMEDA-SHOCK trial highlighted CRT-targeted resuscitation, a subset of patients with a normalized CRT may still have impaired tissue oxygen balance. The oxygen extraction ratio (O₂ER) can deviate in two directions: a high O₂ER (>30%) suggests oxygen delivery that is insufficient for demand (e.g., low cardiac output, anemia), whereas a low O₂ER (<20%, with high central venous oxygen saturation) may reflect microcirculatory shunting and cytopathic hypoxia.

Primary aim. To determine the prevalence of the "discordant" phenotype-defined as a normalized CRT with an abnormal O₂ER at hour 6 of resuscitation-and to evaluate its association with 28-day mortality.

Secondary aims. (1) To examine the association between CRT/O₂ER-defined perfusion phenotypes and 28-day mortality, ICU and hospital length of stay, duration of mechanical ventilation, vasopressor-free days, and need for renal replacement therapy; (2) to validate the proposed O₂ER >30% threshold using ROC curve analysis and identify the optimal cut-off for mortality in this cohort; (3) to assess whether the discordant phenotype is an independent predictor of mortality after adjustment for age, APACHE II score, lactate, and noradrenaline dose using multivariable analysis; (4) to examine the relationship of discordance with complementary perfusion markers (lactate clearance, mottling score, venoarterial CO₂ difference).

Design and setting. Prospective, single-center, observational cohort study in an intensive care unit. Consecutive adult patients diagnosed with septic shock according to the Surviving Sepsis Campaign (SSC) 2026 guideline will be enrolled. Time zero (Hour 0) is defined as the time of vasopressor (noradrenaline) initiation.

Measurements. While patients continue standard care, serial clinical and laboratory measurements are recorded at hours 0, 6, 12, and 24, and organ function at hour 72. CRT is measured in a standardized manner on the ventral surface of the distal phalanx of the right index finger after 10 seconds of firm pressure. O₂ER is calculated as (SaO₂ - ScvO₂) / SaO₂. At hour 6, CRT and blood gas sampling are performed simultaneously (within 15 minutes). Inter-rater reliability of CRT is assessed in the first 20-30 patients by two independent, blinded observers (ICC for continuous values; Cohen's kappa for the ≤3 s normal/abnormal classification).

Phenotype grouping (Hour 6). Group 1 - Concordant normal (CRT ≤3 s + O₂ER 20-30%); Group 2a - Discordant, high O₂ER (CRT ≤3 s + O₂ER >30%); Group 2b - Discordant, low O₂ER (CRT ≤3 s + O₂ER <20%); Group 3 - Concordant abnormal (CRT >3 s + abnormal O₂ER). The primary group of interest is the combined discordant phenotype (Group 2a + Group 2b).

Outcomes. Primary outcome: 28-day mortality (counted from Hour 0). Secondary outcomes: ICU and hospital length of stay, duration of mechanical ventilation, time to vasopressor weaning, vasopressor-free days, hour-72 organ function (SOFA-2, ongoing vasopressor/ventilation, lactate), and need for renal replacement therapy.

Sample size and statistics. A target of approximately 100 consecutive patients was chosen so that an expected discordance prevalence of ~30% can be estimated with a 95% confidence interval half-width of ±9%. Descriptive statistics, normality testing (Shapiro-Wilk), and appropriate parametric/non-parametric group comparisons will be used. The prevalence of the discordant phenotype will be reported with 95% CI. ROC analysis (with AUC) will evaluate the O₂ER threshold for mortality. Multivariable binary logistic regression (parsimonious model: phenotype, APACHE II, lactate; events-per-variable ≈12) will identify independent predictors of mortality, reported as odds ratios with 95% CI. Survival across phenotype groups will be estimated by Kaplan-Meier analysis and compared with the log-rank test. Statistical significance is set at p < 0.05.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Tugba Yesilyurt Dogu, Intensive Medicine Care Fellow; Phone Number: +9005535150847; Email: tugbaayesilyurt@gmail.com

Study Locations

• Turkey (Türkiye)
  • Istanbul, Turkey (Türkiye)
    • Recruiting
    • Başakşehir Çam and Sakura City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Consecutive adult patients (≥18 years) admitted to a single-center intensive care unit and diagnosed with septic shock according to the Surviving Sepsis Campaign (SSC) 2026 guideline, who already have a central venous catheter and an arterial line in place as part of their clinical care. Patients are enrolled from all admission sources (emergency department, ward, operating room, or external referral) and followed prospectively while receiving standard treatment. Patients with active bleeding, ongoing ECMO, conditions that make capillary refill time measurement unreliable (e.g., Raynaud phenomenon or significant peripheral vascular disease), death within the first 6 hours, or inability to obtain hour-6 CRT or blood gas measurements are not included.

Description

Inclusion Criteria:

• Age ≥ 18 years
• Diagnosis of septic shock according to the Surviving Sepsis Campaign (SSC) 2026 guideline
• Presence of both a central venous catheter and an arterial line

Exclusion Criteria:

• Active bleeding
• Ongoing extracorporeal membrane oxygenation (ECMO)
• Raynaud phenomenon or significant peripheral vascular disease that makes capillary refill time measurement unreliable (e.g., critical ischemia, amputation, digital ulcer/necrosis, or inability to measure on the right index finger)
• Death within the first 6 hours
• Inability to obtain hour-6 CRT or blood gas (phenotyping not possible)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

septic schoc cohort; Consecutive adult patients (≥18 years) admitted to the intensive care unit and diagnosed with septic shock according to the Surviving Sepsis Campaign (SSC) 2026 guideline, who have pre-existing central venous and arterial catheters. Patients are prospectively followed while receiving standard care, with serial measurements at hours 0, 6, 12, and 24 (time zero = vasopressor initiation). At hour 6, patients are classified into perfusion phenotypes based on capillary refill time (CRT) and oxygen extraction ratio (O₂ER): concordant normal, discordant with high O₂ER, discordant with low O₂ER, and concordant abnormal. The primary group of interest is the combined discordant phenotype (normalized CRT with abnormal O₂ER).

Diagnostic test: Capillary refill time (CRT); Non-invasive, standardized bedside measurement of capillary refill time on the right index finger.; Diagnostic test: Oxygen extraction ratio (O₂ER) assessment; Oxygen extraction ratio calculated as (SaO₂ - ScvO₂)/SaO₂ from routinely obtained arterial and central venous blood gases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of the discordant CRT-O₂ER phenotype	Proportion of patients classified as having a discordant perfusion phenotype (normalized CRT ≤3 s with an abnormal O₂ER, i.e., >30% or <20%; combined Group 2a + Group 2b) at hour 6, reported with 95% confidence interval.	At hour 6 of resuscitation (6 hours after vasopressor initiation)
28-day all-cause mortality	All-cause mortality at 28 days, and its association with the hour-6 perfusion phenotype.	28 days from Hour 0 (vasopressor initiation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU length of stay	Duration of intensive care unit stay in days.	Through study completion, up to 28 days
Hospital length of stay	Duration of hospital stay in days.	Through study completion, up to 28 days
Duration of mechanical ventilation	Total days on mechanical ventilation (0 if never ventilated).	Through study completion, up to 28 days
Time to vasopressor weaning	Time in hours to sustained vasopressor discontinuation (off ≥24 continuous hours), measured from Hour 0.	From Hour 0 up to 28 days
Vasopressor-free days	Number of days alive and free of vasopressor support within 28 days.	28 days
Organ dysfunction at hour 72	SOFA-2 score at hour 72, together with ongoing vasopressor/mechanical ventilation status and lactate level.	Hour 72
Need for renal replacement therapy (RRT)	Proportion of patients requiring newly initiated RRT within 28 days (chronic dialysis patients excluded from the "new" category).	Within 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance of the O₂ER threshold for mortality	Discriminative ability of O₂ER for 28-day mortality assessed by ROC analysis (area under the curve), with identification of the optimal cut-off and comparison to the literature threshold of 30%.	Hour 6 measurement; mortality at 28 days
Inter-rater reliability of CRT measurement	Agreement of hour-6 CRT between two independent, blinded observers; intraclass correlation coefficient (ICC) for continuous values and Cohen's kappa for the ≤3 s normal/abnormal classification.	Hour 6, first 20-30 patients

Collaborators and Investigators

• Sponsor: Istanbul University - Cerrahpasa
• Collaborators: Başakşehir Çam & Sakura City Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 17, 2026
• Primary Completion (Estimated): June 17, 2027
• Study Completion (Estimated): July 17, 2027

Study Registration Dates

• First Submitted: August 15, 2026
• First Submitted That Met QC Criteria: August 15, 2026
• First Posted (Actual): August 19, 2026

Study Record Updates

• Last Update Posted (Actual): August 19, 2026
• Last Update Submitted That Met QC Criteria: August 15, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Lactate; Microcirculation; Tissue Perfusion; Capillary Refill Time; ScvO2; Observational Cohort Study; Oxygen Extraction Ratio; Hemodynamic Coherence
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Sepsis; Shock, Septic; Diagnostic Techniques and Procedures; Diagnosis; Physical Examination
• Other Study ID Numbers: KAEK-11/29.07.2026.276 (Other Identifier: BASAKSEHİR CAM AND SAKURA CITY HOSPITAL)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No