To investigate the relation between a preoperative abnormal iron status and packed red blood cell transfusion, adverse event and change in disability.To investigate the association of the individual preoperative iron status abnormalities (low iron…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
- Cardiac therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters are perioperative levels of haemoglobin, mean corpuscular
volume (MCV), reticulocyte count, reticulocyte haemoglobin content, red blood
cell count, red cell distribution width (RDW), ferritin, transferrin,
transferrin saturation (TSAT), serum iron, vitamin B12, folate, C-reactive
protein (CRP), creatinine, eGFR.
Anaemia and iron status are defined as:
- Anaemia: haemoglobin level < 8.1 mmol/l for men and < 7.5 mmol/l for women
- Normal iron status: ferritin 30-300 µg/l, TSAT 20-50% and CRP < 5mg/l
- Abnormal iron status (one of the following): low iron store = ferritin < 100
µg/l, absolute iron deficiency: ferritin < 30 µg/l OR ferritin < 100 µg/l and
TSAT < 20% postoperatively (i.e. if CRP > 5 mg/l) OR reticulocyte haemoglobin
count < 28 pg, functional iron deficiency: ferritin 100-500 µg/l and TSAT <
20%, iron sequestration: ferritin > 100 µg/l, TSAT <20% and CRP > 5 mg/l
Low levels of erytroid maturation factors are defined as vitamin B12 level <
200 pmol/l and folate level < 9 nmol/l.
Primary study endpoint is 30-day packed red blood cell transfusion-free
survival.
Secondary outcome
30-day adverse event-free survival. Adverse events are (one of the following):
postoperative infection (pneumonia (purulent sputum, positive sputum or blood
culture and clinical symptoms, e.g. cough, fever or consolidation on chest
radiograph), sepsis (qSOFA score *2 in response to an infection: one point for
any of the following, glascow coma scale a <15, respiratory rate >21, systolic
blood pressure < 100mmHg), surgical site infection:, wound infection (purulent
drainage from superficial incision or deliberate opening of superficial
incision by surgeon and pain, tenderness, swelling or redness), mediastinitis
(an organism isolated from culture of mediastinal tissue or fluid OR evidence
of mediastinitis seen during operation OR presence of either chest pain,
sternal instability, or fever (>38°C), and purulent drainage from the
mediastinum), urinary tract infection (urinary tract symptoms or fever and
urine culture with no more than 2 species of organisms identified with at least
one of which is a bacterium of *105 CFU/ml), central line associated
bloodstream infection (laboratory confirmed bloodstream infection in a patient
where the central line was in place for > 2 calender days on the day of the
event AND one of the following criteria: 1. patient has a recognized pathogen
cultured from one or more blood cultures AND pathogen cultured is not related
to an infection at another site 2. At least one of the following signs fever,
chills, hypotension AND organism cultured from blood is not related to an
infection at another site AND the same matching organism is cultured from two
or more blood cultures on separate occasions)
Other
- acute kidney injury (increase in serum creatinine of * 26 µmol/l within 48
hours of surgery or an increase in serum creatinine tot 150% or more within 7
days or urine volume < 0.5ml/kg/h for 6 hours within 7 days)
- renal replacement therapy within 7 days
- stroke (clinical diagnosis of acute transient ischemic attack (TIA) or
cerebrovascular accident (CVA))
- myocardial infarction (elevated hs-cTn in combination with clinical symptoms
or electrocardiography changes)
- 30-day mortality (+time)
Disability (measured with the World Health Organization Disability Assessment
Schedule (WHODAS 2.0, 12-item version) before and 120 days after surgery. Each
item is attributed 0 to 4 points (0=none, 1=mild, 2=moderate, 3=severe and
4=extreme). The total score, between 0 and 48, is then divided by 48 and
multiplied by 100 to convert it to a percentage of the maximum disability
score.
Background summary
Over one-third of patients undergoing cardiac surgery suffers from preoperative
anaemia. Preoperative anaemia is an independent predictor of transfusion of
packed red blood cells, which occurs in 30 to 60% of patients. Several
observational studies have shown that packed red blood cell transfusion is
associated with adverse outcome. For example, transfusion is associated with
infection, renal insufficiency, mortality and increased costs.
Functional iron deficiency is the most common cause of preoperative anaemia in
cardiac surgical patients. In addition to its essential role in erythropoiesis,
iron is vital for cellular energy metabolism and immune function.
A retrospective cohort study in patients undergoing major surgical procedures,
including cardiac surgery, suggested that approximately 60% of surgical
patients have alterations in iron status, such as low iron stores, absolute
iron deficiency, functional iron deficiency or iron sequestration before
surgery. This is aggravated in the perioperative period as haemodilution during
cardiopulmonary bypass, surgical blood loss and repeated blood sampling lead by
definition to some degree of iron depletion. The postoperative iron status,
however, is infrequently investigated after cardiac surgery. Commonly used iron
store parameters such as ferritin levels are affected by postoperative
inflammation, which makes it difficult to distinguish iron deficiency from
other causes of anaemia. In a recent international consensus statement specific
recommendations were made for diagnosing alterations in iron status even in the
presence of inflammation.
Until now, the relationship between iron status abnormalities and outcome after
cardiac surgery is unclear. In a pilot study, patients with preoperative iron
deficiency received more packed red blood cells units than patients without
iron deficiency (2 vs. 0, respectively, P < 0.05) and more often reported
fatigue. Another exploratory study in cardiac surgical patients showed that
iron deficiency was associated with an increased length of hospital stay and
fewer days alive and out of the hospital.
If perioperative iron deficiency is associated with transfusion of packed red
blood cells or adverse events in cardiac surgical patients, correction of
perioperative iron deficiency by iron replacement may reduce the transfusion
rate and improve outcome. Currently, limited evidence exists on perioperative
iron therapy in patients undergoing cardiac surgery.
The goal of this study is to investigate the association between an abnormal
iron status and transfusion of packed red blood cells, adverse events and
disability in patients undergoing cardiac surgery.
Study objective
To investigate the relation between a preoperative abnormal iron status and
packed red blood cell transfusion, adverse event and change in disability.
To investigate the association of the individual preoperative iron status
abnormalities (low iron stores, absolute iron deficiency, functional iron
deficiency and iron sequestration) with transfusion of packed red blood cells.
To investigate the association of an abnormal iron status at the day of
hospital discharge with change in disability
Study design
Multicenter, prospective, observational study.
Study burden and risks
In each patient two blood samples will be drawn for analysis. The first blood
sample is collected during routine preoperative blood sampling the day before
surgery or, on the day of surgery, from an arterial line, which is routinely
used in patients undergoing cardiac surgery. The second blood sample is
collected at hospital discharge and this will often coincidence with routine
blood sampling. Patients will be asked to submit a disability questionnaire
(average interview time is 5 minutes) before and after surgery. There are no
direct risks or benefits for patients included in the study.
Molengracht 21
Breda 4818CK
NL
Molengracht 21
Breda 4818CK
NL
Listed location countries
Age
Inclusion criteria
Elective cardiac surgery (CABG, aortic valve replacement, mitral valve
replacement, aortic surgery, Maze, or combined surgery)
On-pump surgery
Age * 60 years
Exclusion criteria
Emergent or urgent surgery
Acute infection
Haemochromatosis
Illiteracy
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL68297.100.18 |