13 research outputs found
Double Blind, Randomised Controlled Trial
Purpose Surgical patients are at high risk for developing infectious
complications and postoperative delirium. Prolonged infections and delirium
result in worse outcome. Granulocyte-macrophage colony-stimulating factor (GM-
CSF) and influenza vaccination are known to increase HLA-DR on monocytes and
improve immune reactivity. This study aimed to investigate whether GM-CSF or
vaccination reverses monocyte deactivation. Secondary aims were whether it
decreases infection and delirium days after esophageal or pancreatic resection
over time. Methods In this prospective, randomized, placebo-controlled,
double-blind, double dummy trial setting on an interdisciplinary ICU of a
university hospital 61 patients with immunosuppression (monocytic HLA-DR
[mHLA-DR] <10,000 monoclonal antibodies [mAb] per cell) on the first day after
esophageal or pancreatic resection were treated with either GM-CSF (250
μg/m2/d), influenza vaccination (Mutagrip 0.5 ml/d) or placebo for a maximum
of 3 consecutive days if mHLA-DR remained below 10,000 mAb per cell. HLA-DR on
monocytes was measured daily until day 5 after surgery. Infections and
delirium were followed up for 9 days after surgery. Primary outcome was HLA-DR
on monocytes, and secondary outcomes were duration of infection and delirium.
Results mHLA-DR was significantly increased compared to placebo (p < 0.001)
and influenza vaccination (p < 0.001) on the second postoperative day.
Compared with placebo, GM-CSF-treated patients revealed shorter duration of
infection (p < 0.001); the duration of delirium was increased after
vaccination (p = 0.003). Conclusion Treatment with GM-CSF in patients with
postoperative immune suppression was safe and effective in restoring monocytic
immune competence. Furthermore, therapy with GM-CSF reduced duration of
infection in immune compromised patients. However, influenza vaccination
increased duration of delirium after major surgery
Leukocytes over time.
<p>From day of surgery (dOs) until day 5 after surgery (<i>pod5</i>) between groups. Leukocytes significantly increased on pod2 (p = 0.003) after stimulation with GM-CSF.</p
Number of infection days.
<p>From day 1 (<i>pod1</i>, before intervention) until day 9 after surgery (<i>pod9</i>). Between all three groups: p = 0.001. Placebo vs. GM-CSF: p < 0.001. Placebo vs. vaccination: p = 0.068. Vaccination vs. GM-CSF: p = 0.044.</p
Post-interventional course and outcome parameters.
<p>Continuous quantities in median (25%-75% percentiles), frequencies with n; APACHE, Acute Physiology and Chronic Health Evaluation; SAPS, Simplified Acute Physiology Score; SOFA, Sequential Organ Failure Assessment; TISS, Therapeutic Intervention Scoring System; ICU, Intensive Care Unit.</p
Number of delirium days (DDS > 3).
<p>From day 1 (<i>pod1</i>, before intervention) until day 9 after surgery (<i>pod9</i>). Between all three groups: p = 0.004. Placebo vs. GM-CSF: p = 0.737. Placebo vs. vaccination: p = 0.003. Vaccination vs. GM-CSF: p = 0.007.</p
Consort diagram.
<p><i>dBs</i>, day before surgery. <i>dOs</i>, day of surgery. <i>pod</i>, postoperative day.</p
Influence of Granulocyte-Macrophage Colony-Stimulating Factor or Influenza Vaccination on HLA-DR, Infection and Delirium Days in Immunosuppressed Surgical Patients: Double Blind, Randomised Controlled Trial
<div><p>Purpose</p><p>Surgical patients are at high risk for developing infectious complications and postoperative delirium. Prolonged infections and delirium result in worse outcome. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and influenza vaccination are known to increase HLA-DR on monocytes and improve immune reactivity. This study aimed to investigate whether GM-CSF or vaccination reverses monocyte deactivation. Secondary aims were whether it decreases infection and delirium days after esophageal or pancreatic resection over time.</p><p>Methods</p><p>In this prospective, randomized, placebo-controlled, double-blind, double dummy trial setting on an interdisciplinary ICU of a university hospital 61 patients with immunosuppression (monocytic HLA-DR [mHLA-DR] <10,000 monoclonal antibodies [mAb] per cell) on the first day after esophageal or pancreatic resection were treated with either GM-CSF (250 μg/m<sup>2</sup>/d), influenza vaccination (Mutagrip 0.5 ml/d) or placebo for a maximum of 3 consecutive days if mHLA-DR remained below 10,000 mAb per cell. HLA-DR on monocytes was measured daily until day 5 after surgery. Infections and delirium were followed up for 9 days after surgery. Primary outcome was HLA-DR on monocytes, and secondary outcomes were duration of infection and delirium.</p><p>Results</p><p>mHLA-DR was significantly increased compared to placebo (p < 0.001) and influenza vaccination (p < 0.001) on the second postoperative day. Compared with placebo, GM-CSF-treated patients revealed shorter duration of infection (p < 0.001); the duration of delirium was increased after vaccination (p = 0.003).</p><p>Conclusion</p><p>Treatment with GM-CSF in patients with postoperative immune suppression was safe and effective in restoring monocytic immune competence. Furthermore, therapy with GM-CSF reduced duration of infection in immune compromised patients. However, influenza vaccination increased duration of delirium after major surgery.</p><p>Trial Registration</p><p><a href="http://www.controlled-trials.com" target="_blank">www.controlled-trials.com</a><a href="http://www.controlled-trials.com/ISRCTN27114642?q=ISRCTN27114642%20&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search" target="_blank">ISRCTN27114642</a></p></div
Infection and delirium days (DDS > 3).
<p>Overall (Kruskal-Wallis): <b>Infection days</b>: p = 0.001; <b>Delirium days (DDS > 3)</b>: p = 0.004; IQR: Interquartile Range.</p
Monocytic HLA-DR (mHLA-DR) on day 1 (<i>pod1)</i> and day 2 <i>(pod2)</i> after surgery.
<p>Paired Wilcoxon Test (<b><i>pod1 versus pod2</i></b>): Placebo: p = 0.0027; Vaccination: p = 0.013; GM-CSF: p < 0.001; Overall (Kruskal-Wallis): <b><i>pod1</i></b>: p = 0.667; <b><i>pod2</i></b>: p < 0.001; <b><i>pod1 –pod2</i></b>: p < 0.001; IQR: Interquartile Range.</p
Basic patient characteristics and pre-interventional course.
<p>Continuous quantities in median (25%-75% percentiles), frequencies with n (%); NRS, Numeric Rating Scale; <i>dBs</i>, day before surgery; <i>pod1</i>, day 1 after surgery; ASA, American Society of Anesthesiologists; AUDIT score, Alcohol Use Disorders Identification Test; PONV, postoperative nausea and vomiting; APACHE, Acute Physiology and Chronic Health Evaluation; SAPS, Simplified Acute Physiology Score; SOFA, Sequential Organ Failure Assessment; TISS, Therapeutic Intervention Scoring System; ICU, Intensive Care Unit.</p