52 in 52 – #8: The “ANDROMEDA-SHOCK” Trial
- Aug 17th, 2022
- Brannon Inman
Welcome back to the “52 in 52” series. This collection of posts features recently published must-know articles. Our eighth post looks at the ANDROMEDA-SHOCK trial.
Author: Brannon Inman (Chief Resident, Emergency Medicine Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)
Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock
AKA: The “ANDROMEDA-SHOCK” Trial
In patients with septic shock, does peripheral perfusion guided resuscitation improve 28 day all cause mortality compared to lactate guided resuscitation
- Multicenter randomized controlled, superiority trial
- Included patents in 28 hospitals in Central and South America (Argentina, Chile, Colombia, Ecuador, Uruguay)
- Included patients > 18 years
- Admitted to the ICU with early (< 4 hours) septic shock defined by the Sepsis-3 criteria
- Lactate >2
- Suspected/confirmed infection
- Vasopressors to maintain map ≥65 despite 20mL/kg over 60 minutes
- Exclusion criteria included:
- Severe acute respiratory distress syndrome
- Do-not-resuscitate status (DNR)
- Use of capillary refill time (CRT)
- CRT was measured every 30 min until normalization then hourly for the subsequent 8 hours
- Resuscitation targeted to CRT < 3 seconds
- “CRT was measured by applying firm pressure to the ventral surface of the right index finger distal phalanx with a glass microscope slide. The pressure was increased until the skin was blank and then maintained for 10 seconds. The time for return of the normal skin color was registered with a chronometer, and a refill time greater than 3 seconds was defined as abnormal.” – excerpt from text
- Lactate guided resuscitation
- Lactate measured every 2 hours for 8 hours with goal of 20% reduction in 2 hours
Both groups were resuscitated in a similar fashion according to the following treatment protocol:
In the event patients were not meeting treatment arm requirements, the following actions were taken:
- Patients were first assessed for fluid responsiveness (blue box above)
- Stroke volume variation or passive leg raise
- 500 cc IVF boluses given until target met or no longer fluid responsive
- Vasopressor test (green box above)
- Patients with history of HTN had trial of MAP 80-85 mmHg using a steadily increasing norepinephrine infusion, followed by reassessment
- Inotrope challenge (red box above)
- If patient not responsive to the above interventions, they had a trial of dobutamine or milrinone
- 424 patients randomized, with 416 completing the trial
- Day 28 mortality
- 34.9% in the CRT group
- 43.4% in the lactate group
- Hazard ratio 0.75 (95% CI 0.55-1.02)
- No difference in secondary outcomes: organ dysfunction at 72 hours after randomization, death within 90 days, mechanical ventilation free days, renal replacement therapy, vasopressor-free days within 28 days, ICU/hospital LOS
- Negative trial
- Overall, both groups were well balanced with good protocol adherence (violations in 13.7% CRT patients and 10.8% lactate patients). There was a trend but no statistically significant reduction in mortality with use of peripheral perfusion compared to measurement of serum lactate. There was an 8.5% mortality difference which is nothing to laugh at.
- This trial was set up as a superiority trial. It would be interesting to see how the results would be had the trial been conducted as a non-inferiority trial.
- The trial was underpowered. The original calculations were to detect a mortality difference of 15%. They likely set the study’s mortality difference too high to be feasible. This set the trial up for a high chance of Type II error (falsely accept the null).
- It was also non-blinded, which may result in provider bias.
- Overall, CRT-guided resuscitation is probably at least as good as resuscitation based on lactate.
I practice in a country where measurement of serum lactate is mandated for reimbursement. Therefore, I will continue to measure serum lactate. However, this trial suggests the use of peripheral perfusion markers such as capillary refill is a potentially viable and useful bedside assessment I can use in the ED and ICU to quickly gauge how my resuscitation is going for critically ill septic patients.
- Hernández G, Ospina-Tascón GA, Damiani LP, et al. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019;321(7):654-664. doi:10.1001/jama.2019.0071