Lactate Clearance Goal-directed Therapy in Sepsis

Sepsis remains a great challenge for clinicians, early goal-directed therapy(EGDT), referring to a number of target-achieving indicators including systemic central venous oxygen saturation(ScvO2) after initial fluid resuscitation within 6 hours, has been one of the main treatment for sepsis. ScvO2 is the only indicator that reflects tissue oxygen metabolism. However, there're studies confirmed that ScvO2 oriented EGDT cannot reduce the mortality of sepsis. So it is important to find out a more effective indicator. Lactic acid is a product of anaerobic metabolism of the body, lactate clearance has been found to effectively predict the prognosis of sepsis. Few studies have shown that lactate clearance oriented fluid resuscitation can be of benefit in patients with sepsis. Nevertheless, whether lactate clearance could be combined with sepsis Bundle as a new marker to improve the prognosis remains a problem. The objective of this study is to discuss the feasibility of lactate clearance oriented sepsis treatment through multi-center clinical trial.

• Lactate clearance 10% target group (Behavioral), also known as Lac% 10% group: Participants receive the protocolized resuscitation to achieve the goal of 10-percent lactate clearance every two hours within the initial six hours of treatment.
• Lactate clearance 20% target group (Behavioral), also known as Lac% 20% group: Participants receive the protocolized resuscitation to achieve the goal of 20-percent lactate clearance every two hours within the initial six hours of treatment.
• Standard EGDT group (Behavioral), also known as EGDT group: Participants receive the strategy of early goal-directed treatment of sepsis fluid resuscitation.

Primary outcomes

• 28-d mortality [Four years]: All-cause mortality at 28 days

Secondary outcomes

• ICU Length of stay [Four years]: Length of stay in the intensive care unit (ICU)
• Hospital Length of stay [Four years]: Length of stay in hospital
• 90-d mortality [Four years]: All-cause mortality at 90 days
• In-hospital mortality [Four years]: All-cause mortality during hospitalization
• In-ICU mortality [Four years]: All-cause mortality during ICU stay
• Administered treatments [Four years]: Administered treatments included: crystalloid volume, vasopressor administered, dobutamine, red blood cell(RBC) transfusion, mechanical ventilation, renal-replacement therapy
• SOFA at 24h [Four years]: Sequential Organ Failure Assessment(SOFA) at 24 hours
• Adverse events [Four years]: Proportion of patients reporting treatment-emergent adverse events

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Older than 17 years old.
* Primary diagnosis is sepsis, means being confirmed or suspected infection while have at least 2 points of quickSOFA(qSOFA).
* Be transferred to intensive care unit (ICU) for the first time during this hospitalization.
* Elevated lactate ≥3.0mmol/L.

Exclusion Criteria:

* Acute hemorrhage uncontrolled.
* Pregnancy.
* Known liver disease - Child-Pugh classes C, acute hepatic failure, severe hepatopathy accompany with prominent portal hypertension.
* Known being in an immunosuppressive state:

  1. Suffering from any disease that is unrelated with sepsis that severely inhibits the immune to infection, such as: active hematological or lymphoma malignancy, or during immunosuppressive therapy, such as chemotherapy or radiotherapy.
  2. Known human immunodeficiency virus (HIV) serology positive.
* Known chronic kidney disease.
* Suffering from any disease that affects lactate kinetics, such as mitochondrial encephalopathy, congenital hyperlipidemia, Wernicke encephalopathy, etc. Or other probable cause of hyperlactatemia.
* Took any drugs that affect lactate kinetics within the effective time window, such as taking metformin or phenylephrine within 1 week.
* Suffering from any disease that restricts resuscitation, such as heart failure, cardiac surgery, severe heart disease etc, or suffered from a cardio-pulmonary resuscitation,.

• Study Protocol and Statistical Analysis Plan (PDF, 2017-08-07)
• Informed Consent Form (PDF, 2017-08-07)

• Chen Zhongqing, Ph.D, Study chair, Southern Medical University, China