Red Blood Cell Transfusion Improves Perfusion Parameters in Septic Shock Patients With Hypoperfusion

Red Blood Cell Transfusion Improves Perfusion Parameters in Septic Shock Patients With Hypoperfusion: a Prospective Randomized Study

The purpose of this study was to evaluate the immediate effects of red blood cells transfusion on central venous oxygen saturation and lactate levels in septic shock patients randomized to two different hemoglobin levels.

The influence of red blood cell (RBC) transfusion on the adequacy of oxygen delivery (DO2) and supply (VO2) could be assessed by systemic oxygen variables such as central venous oxygen saturation (ScvO2) and lactate levels. Although it is not clear that alterations in these parameters actually represent an improvement in the DO2/VO2 ratio, they might represent a better transfusion trigger than the absolute hemoglobin value.

Patients admitted with a diagnosis of septic shock and hemoglobin levels lower than 9.0 g/dL , less than 48 hours of shock diagnosis, were included, a central venous catheter in the superior vena cava and signed informed consent. The investigators randomized all patients into two groups. Patients in the liberal group received transfusions immediately, as the objective was to maintain hemoglobin levels above 9.0 g/dL. In the restrictive group, transfusion was withheld until their hemoglobin levels fell below 7.0 g/dL.

Each time a patient received a transfusion, the investigators collected a set of laboratory tests, including hemoglobin levels, ScvO2 and lactate, at two time points, immediately before transfusion and one hour after its ending.

The sample size was calculated by considering that in 80% of the transfusions in patients in the restrictive group ScvO2 would improve compared to only 45% of those in the liberal group, with an alpha error of 0.05 and 80% power. Improvement was defined as an increase of 5% over the pre-transfusion ScvO2. Twenty-eight transfusions in each group would be necessary, but to correct for potential non-parametric distribution of the main variables, the number was adjusted to 35 transfusions in each group.

Trends in ScvO2 and lactate were categorized as worsening or improving. The investigators defined improvement when ScvO2 reached 70% in patients with baseline levels below this threshold or when there was an absolute increase of at least 5% after transfusion. Any increase in patients with previous ScvO2 ≥ 70% was considered to be "no change". Worsening was defined as a reduction of 5% in the previous levels or a decline to less than 70% in patients with pre-transfusion levels in the range of 70 to 75%. The investigators also carried out a ROC curve analysis to assess the accuracy of the pre-transfusion hemoglobin levels, pre-transfusion lactate and pre-transfusion ScvO2 in predicting the patients whose ScvO2 would increase more than 5% with transfusion. For this analysis, the investigators used a different approach because it would also be necessary to analyze patients with a lower chance of response to assess the prediction of response. Thus, this analysis included all patients with ScvO2 below 75%, rather than only those below 70%. As before, the investigators defined improvement as any increase ≥ 5%. The investigators did not consider patients with levels above 75% in this analysis, as the physiological interpretation of this situation is challenging. The investigators considered as altered any lactate levels above 1.5 times the reference level, and a change ≥ 10% was defined as improvement or worsening. In patients with baseline normal levels, the status was recorded as worsening if a 10% increase was detected. Afterwards, the investigators tested the association between these categorized variables and the baseline levels of hemoglobin. The impact on perfusion was also assessed by the determination of Δlactate (lactate post-transfusion x 100/lactate pre-transfusion) and ΔScvO2 (ScvO2 post-transfusion x 100/ScvO2 pre-transfusion), and their correlation with the baseline hemoglobin levels was analyzed using the Spearman correlation test.

In all tests, the results were considered significant if the p level was lower than 0.05.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Other: packed red blood cell transfusion

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 04023-900
    • Hospital Sao Paulo - Universitary hospital of Sao Paulo Federal University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age over 18 years old
• less than 48 hours of shock diagnosis
• hemoglobin levels lower than 9.0 g/dL
• a central venous catheter in the superior vena cava
• signed informed consent. The exclusion criteria were

Exclusion Criteria:

• pregnancy
• known coronary disease
• active bleeding
• previous participation in the study.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: liberal group; Patients in the liberal group received transfusions immediately, as the objective was to maintain hemoglobin levels above 9.0 g/dL.	Other: packed red blood cell transfusion; Patients wil be randomized en two groups, in the liberal group they must received transfusions immediately, as the objective was to maintain hemoglobin levels above 9.0 g/dL. In the restrictive group they will receive transfusion to maintain hemoglobin levels above 7.0g/dL
Active Comparator: restrictive group; Patients in the liberal group received transfusions immediately, as the objective was to maintain hemoglobin levels above 7.0 g/dL.	Other: packed red blood cell transfusion; Patients wil be randomized en two groups, in the liberal group they must received transfusions immediately, as the objective was to maintain hemoglobin levels above 9.0 g/dL. In the restrictive group they will receive transfusion to maintain hemoglobin levels above 7.0g/dL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Evaluate the change in baseline levels of lactate and central venous saturation effects after red blood cells transfusion in patients of septic shock	The purpose of this study was to evaluate the effects of red blood cells transfusion on central venous oxygen saturation and lactate levels after 1 hour in septic shock patients randomized to two different hemoglobin levels

Collaborators and Investigators

• Sponsor: Bruno Franco Mazza

Publications and helpful links

General Publications

• Mazza BF, Freitas FG, Barros MM, Azevedo LC, Machado FR. Blood transfusions in septic shock: is 7.0 g/dL really the appropriate threshold? Rev Bras Ter Intensiva. 2015 Jan-Mar;27(1):36-43. doi: 10.5935/0103-507X.20150007. Epub 2015 Mar 1.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: May 24, 2012
• First Submitted That Met QC Criteria: May 31, 2012
• First Posted (Estimate): June 5, 2012

Study Record Updates

• Last Update Posted (Estimate): June 5, 2012
• Last Update Submitted That Met QC Criteria: May 31, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Ischemia; Shock, Septic; Erythrocyte Transfusion
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: 1177/04