Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy: A Randomized Clinical Trial
Dr. Alan E. Jones, MD, Dr. Nathan I. Shapiro, MD, MPH, Dr. Stephen Trzeciak, MD, MPH, Dr. Ryan C. Arnold, MD, Ms. Heather A. Claremont, BFA, and Dr. Jeffrey A. Kline, MD for the Emergency Medicine Shock Research Network (EMShockNet) Investigators
The purpose of this study was to test the hypothesis of non inferiority between lactate clearance and central venous oxygen saturation (ScvO2) as goals of early sepsis resuscitation.
A multi-centre, prospective, randomised, parallel group, non inferiority trial
Two or more from the SIRS criteria
Confirmed or presumed infection
Hypoperfusion evidenced by either a systolic blood pressure less than 90 mm Hg after fluid bolus of 20mls/kg or a blood lactate concentration of at least 4 mmol/L
Any primary diagnosis other than sepsis.
Suspected requirement for immediate surgery within 6 hours of diagnosis.
An absolute contraindication to chest or neck central venous catheterization, cardiopulmonary resuscitation.
Transfer from another institution with a sepsis-specific resuscitative therapy underway.
Advanced directive orders that would restrict the study procedure.
Each group received quantitative resuscitation. The SVCO2 group was resuscitated by providing therapy to meet the needs of the central venous pressure, followed by MAP and then SCVO2. All patients received chest or neck central venous catheter capable of measuring continuous ScvO2 (PreSep, Edwards Lifesciences, Irvine, California). These patients had their central venous catheters attached to the monitor. The EDGT protocol was used whereby boluses of fluid were given to achieve a CVP of 8 and dopamine or norepinephrine were administered if this fluid therapy did not achieve a MAP of 65 or above. If SCVO2 was not greater than 70% when these targets were achieved and the heamatocrit was lower than 30% then blood was administered. if the heamatocrit were greater than 30% then a dobutamine infusion was started.
This group went through the same process as above but had their treatment titrated to lactate clearance rather than SCVO2. All patients received chest or neck central venous catheter capable of measuring continuous ScvO2 (PreSep, Edwards Lifesciences, Irvine, California). The lactate clearance was
defined by the equation [(lactateinitial − lactatedelayed)/lactateinitial] × 100%, for which lactate initial was the measurement at the start of the resuscitation and lactate delayed was another measurement after a minimum of 2 hours after resuscitation was initiated. If the lactate clearance was not at least 10% at the first delayed measurement and the hematocrit was less than 30%, packed red blood cells were transfused to achieve a hematocrit of at least 30%. If the lactate clearance remained lower than 10% after the heamatocrit was at least 30%, dobutamine was initiated and titrated in attempts to achieve a lactate clearance of at least 10%.
Primary endpoint – In hospital mortality rate
Secondary endpoint – ICU length of stay, ventilator free days and new onset multiple organ failure.
“A protocol targeting lactate clearance of at least 10% as evidence of adequate tissue oxygen delivery produces a similar short-term survival
rate as a protocol using ScvO2 monitoring.”
Study could not be blinded.
Interventions undertaken when the parameters were below the performance goal were not assessed.
Study conducted at centres which had well established protocols for dealing with the septic patient therefore results may not be generalisable.