In adult patients with early septic shock diagnosed within 4 hours, does a capillary refill time (CRT)‑guided resuscitation strategy improve outcomes compared with usual lactate‑guided care?

Capillary Refill Time-Guided Resuscitation in Early Septic Shock: ANDROMEDA-SHOCK-2 Trial

A personalized hemodynamic resuscitation protocol targeting capillary refill time (CRT) is superior to usual lactate-guided care in adult patients with early septic shock, primarily by reducing the duration of vital organ support. 1

Key Trial Results

The ANDROMEDA-SHOCK-2 trial enrolled 1,467 patients across 86 centers in 19 countries and demonstrated that CRT-targeted resuscitation achieved a win ratio of 1.16 (95% CI, 1.02-1.33; P = .04) for the hierarchical composite outcome of mortality, duration of vital support, and hospital length of stay. 1 The benefit was driven predominantly by a 5.3% absolute reduction in duration of vital support (26.4% vs 21.1% wins), with smaller contributions from mortality (19.1% vs 17.8% wins) and hospital stay (3.4% vs 3.2% wins). 1

The CRT-Targeted Protocol Algorithm

The intervention group measured CRT hourly for 6 hours, and when abnormal (>3 seconds), patients entered a stepwise hemodynamic phenotyping algorithm: 2, 1

Step 1: Pulse Pressure Assessment

• If pulse pressure <40 mmHg: Proceed to fluid responsiveness testing and administer fluids only if responsive. 2
• If pulse pressure ≥40 mmHg: Titrate norepinephrine to maintain diastolic arterial pressure >50 mmHg. 2

Step 2: Echocardiographic Evaluation

• Perform bedside critical care echocardiography to identify cardiac dysfunction (reduced ejection fraction, right ventricular dysfunction, or valvular abnormalities) and guide subsequent management. 2

Step 3: Vasopressor and Inodilator Optimization

• Conduct vasopressor and inodilator tests to further optimize peripheral perfusion if CRT remains abnormal after previous steps. 2

Comparison to Lactate-Guided Resuscitation

The original ANDROMEDA-SHOCK trial (2019) compared CRT-targeted versus lactate-targeted resuscitation in 424 patients and found a non-significant trend toward lower 28-day mortality (34.9% vs 43.4%; HR 0.75,95% CI 0.55-1.02; P = .06) and significantly less organ dysfunction at 72 hours (mean SOFA score 5.6 vs 6.6; mean difference -1.00, P = .045). 3 The ANDROMEDA-SHOCK-2 trial built upon this by incorporating hemodynamic phenotyping and demonstrated clear superiority for the composite outcome. 1

Mechanistic Rationale for CRT Superiority

CRT provides real-time assessment of peripheral perfusion that may prevent over-resuscitation. 4 Lactate elevation in sepsis arises from multiple non-hypoxic mechanisms—including β-adrenergic stimulation, hepatic dysfunction, and accelerated aerobic glycolysis—making it a non-specific indicator of tissue hypoperfusion. 5 Approximately 23% of septic patients exhibit "cryptic shock" (lactate ≥2 mmol/L despite central venous oxygen saturation >70%), reflecting impaired cellular oxygen utilization rather than inadequate oxygen delivery. 5

CRT normalization indicates successful reperfusion almost immediately, allowing clinicians to stop fluid administration before overload occurs, whereas lactate clearance lags behind hemodynamic improvements by hours. 4 This temporal advantage likely explains the reduced duration of vital support in ANDROMEDA-SHOCK-2. 1

Integration with Current Guidelines

The Surviving Sepsis Campaign recommends targeting either lactate normalization or lactate clearance >20% every 2 hours during early septic shock resuscitation, alongside MAP ≥65 mmHg and urine output ≥0.5 mL/kg/h. 6, 5 The ANDROMEDA-SHOCK-2 results suggest that CRT-targeted resuscitation with hemodynamic phenotyping should be considered as an alternative or complementary strategy to lactate-guided care, particularly when bedside echocardiography is available. 1

Practical Implementation

Measure CRT by applying firm pressure to the distal phalanx of the index finger for 10 seconds, then releasing and timing the return of normal color; normal is ≤2 seconds, and >3 seconds is abnormal. 7 In the intervention protocol, CRT is assessed hourly for the first 6 hours after septic shock diagnosis. 2, 1

Key clinical perfusion markers to assess alongside CRT include: mental status (alert vs confused), extremity temperature (warm vs cold), urine output (target ≥0.5 mL/kg/h), and capillary refill time itself (target ≤2 seconds). 8, 7

Critical Caveats

Do not abandon lactate measurement entirely—initial lactate ≥4 mmol/L identifies patients with 46.1% mortality who require immediate protocolized resuscitation, and serial lactate measurements remain valuable for assessing metabolic response. 8, 7 The ANDROMEDA-SHOCK-2 protocol used CRT as the primary target but did not prohibit lactate monitoring. 1

CRT assessment requires training and standardization to minimize inter-observer variability, and ambient temperature can affect measurements (cold environments prolong CRT independent of perfusion status). 3

The hemodynamic phenotyping approach requires bedside echocardiography, which may not be universally available in all centers; however, the pulse pressure and diastolic pressure assessments can be performed with standard arterial line monitoring. 2

Clinical Bottom Line

For adult patients with early septic shock (diagnosed within 4 hours), implement a CRT-targeted resuscitation protocol with hemodynamic phenotyping rather than relying solely on lactate-guided care. 1 This approach reduces the duration of vasopressor, mechanical ventilation, and renal replacement therapy without increasing mortality, representing a more physiologically sound and resource-efficient strategy. 1 The protocol is particularly advantageous when bedside echocardiography is available to guide fluid, vasopressor, and inotrope decisions based on individual hemodynamic phenotypes. 2, 1