Study reference

Study characteristics

Patiënt characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Carson, 2013

Type of study: RCT

Setting:

Country: USA

Source of funding: Funded by National Heart Lung and Blood Institute Grant Number: 1RC2HL101458-01.

Inclusion criteria: (1) greater than 18 years of age; (2) had either (a) ST segment elevation myocardial infarction, (b) Non ST segment elevation myocardial infarction, (c) unstable angina, or (d) stable coronary artery disease undergoing a cardiac catheterization; and (3) had a hemoglobin concentration less than 10 g/dL at the time of random allocation.

Exclusion criteria: active bleeding from cardiac catheterization puncture site, including retroperitoneal, judged to be uncontrolled or needing surgical repair or resulting in hemodynamic instability at any time during the index admission; symptoms of anemia at the time of randomization; or other health concerns

N total at baseline:

Intervention: 55

Control: 55

Important prognostic factors²:

age ± SD:

I: 74.3 ± 11.3

C: 67.3 ± 13.6

Sex:

I: 49% M

C: 51% M

Groups comparable at baseline? Yes, except for age

Describe intervention (treatment/procedure/test):

restrictive transfusion strategy were permitted to receive a transfusion if they developed symptoms related to anaemia. A blood transfusion was also permitted, but not required, in the absence of symptoms if the haemoglobin concentration fell below 8 g/dL. There was no lower threshold for which blood was required in the restrictive group. Blood was to be administered one unit at a time and the presence of symptoms reassessed. Only enough blood was given to relieve symptoms or to increase the haemoglobin concentration above 8 g/dL. Symptoms of anaemia that were indications for transfusion included definite angina requiring treatment with sublingual nitro-glycerine or equivalent therapy, and unexplained tachycardia or hypotension. Leukoreduction was not required.

Describe control (treatment/procedure/test):

liberal transfusion strategy received one unit of packed red blood cells following randomization and then received enough blood to raise the haemoglobin concentration to 10 g/dL or above any time the haemoglobin concentration was detected to be below 10 g/dL during the hospitalization for up to 30 days.

Length of follow-up: We recorded daily haemoglobin concentrations for the first 3 days following randomization. We did not mandate daily measurements thereafter but recorded all other haemoglobin concentrations during the hospitalization (up to 30 days).

All surviving patiënts discharged from the hospital by telephone at 30 days and 6 months after randomization to learn of their vital status and repeated hospital admissions

Loss-to-follow-up:

Intervention: 1

Reasons (describe): Unable to contact patiënt

Control: 0

Patiënt did not receive allocated intervention:

I: 1

Reasons: Transfusion w/o symptoms and Hgb>=8

C: 6

Reasons: Withdrawal transfusion protocol, discharged before transfusion, discharged with Hgb<10

Incomplete outcome data:

-

Outcome measures and effect size (include 95%CI and p-value if available):

Mortality (30 days):

I: 7 (13.0%)

C: 1 (1.8%%)

Length of hospital stay:

Not reported

Blood usage (units):

I: 1.6 (SD 1.1)

C: 0.5 (SD 1.0)

Pneumonia or blood stream infection:

I: 2 (3.7%)

C: 0

Cardiac events:

Myocardial infarction:

I: 7 (13%)

C: 5 (9.1%)

Unscheduled coronary revascularization:

I: 2 (3.7%)

C: 0

Congestive heart failure:

I: 7 (13%)

C: 2 (3.6%)

DVT or pulmonary embolism:

I: 0

C: 1 (1.8%)

acute coronary syndrome or stable angina undergoing cardiac catheterization

Cholette, 2011

Type of study: RCT

Setting: PICU

Country: USA

Source of funding: unknown

Inclusion criteria: infants and children presenting to the university of Rochester Medical Center for elective partial or total cavopulmonary connection (BDG or fontan procedures)

Exclusion criteria: no informed consent

N total at baseline:

Intervention: 31

Control: 31

Important prognostic factors²:

age ± SD:

I: 27 ± 23

C: 32.5 ± 27

Sex:

I: 56.6% M

C: 56.6% M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

Restrictive

Restrictive transfusion group required 10 mL/kg of RBCs for any haemoglobin of 9.0 g/dL accompanied by clinical findings suggestive of symptomatic anemia (i.e. tachycardia and/or hypotension unresponsive to crystalloid or colloid infusion

Describe control (treatment/procedure/test):

Liberal

Liberal transfusion group required 10mL/kg of RBCs for any haemoglobin of 13.0 g/dL regardless of whether there was a clinical indication for a transfusion

Length of follow-up:

Excluded from study:

Intervention: 1

Control: 1

Reasons (describe): Unable to have surgery performed and therefore excluded

Loss-to-follow-up or incomplete outcome data:

none

Outcome measures and effect size (include 95%CI and p-value if available):

Mortality (30 days):

Restrictive: 0

Liberal: 0

Myocardinfarct:

Not reported

Ischemic event:

Not reported

Infectious event:

Not reported

Clinically significant pulmonary complications:

Not reported

Patiënts transfused:

Restrictive: 11

Liberal: 29

Units transfused:

Restrictive: 0.43 ± 0.6

Liberal: 2.1 ± 1.2

No. of days in hospital (median):

Restrictive: 11 (4-78)

Liberal: 9.5 (5-62)

Children with single ventricle physiology

Bij restrictive uitgaan van Hb in combinatie met symptomatic anaemia: is dat vergelijkbaar met de andere studies?

Cooper, 2011

Type of study: RCT

Setting:

Country: USA

Source of funding: supported by the Cardiovascular Research Institute of the Washington Hospital Center and received no external funding

Inclusion criteria: Patiënts admitted with acute myocardinfract (defined as ischemic-type chest discomfort lasting >=30 minutes and associated with a creatine kinase-MB (CK-MB) or cardiac troponin level above the upper limit of normal (determined locally); in whom the hematocrit was <=30% within 72 hours of symptom onset

Exclusion criteria: (1) noncoronary cause for clinical syndrome; (2) active bleeding, defined as overt blood loss accompanied by a decrease in hematocrit of >=5% in the preceding 12 hours; (3) inability or unwillingness to receive RBC transfusion; (4) RBC transfusion within 7 days of enrollment; (5) previous severe transfusion reaction; (6) imminent death; (7) decision to provide limited or comfort care; (8) age <21 years; (9) pregnancy; (10) participation in another clinical trial in which RBC transfusion was a requirement or a component of a primary or secondary end point; and (11) previous participation in the present study.

N total at baseline:

Intervention: 21

Control: 24

Important prognostic factors²:

For example

age ± SD:

I: 70.3 ± 14.3

C: 76.4 ± 13.5

Sex:

I: 54% M

C: 48% M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

conservative transfusion strategy underwent RBC transfusion when their haematocrit decreased <24% with the goal of maintaining a hematocrit from 24% to 27%

Patiënts could receive RBC transfusion for any of the following reasons at the discretion of the treating physician: (1) active bleeding as defined earlier; (2) persistent hypotension related to hypovolemia; (3) active ischemia; and (4) at any time it was determined that it was in a patiënt’s best interest to receive a transfusion. Once the active issue was resolved, transfusion was again administered according to the study protocol

Describe control (treatment/procedure/test):

liberal transfusion strategy underwent RBC transfusion when their hematocrit decreased <30% with the goal of maintaining a hematocrit from 30% to 33%

Patiënts could receive RBC transfusion for any of the following reasons at the discretion of the treating physician: (1) active bleeding as defined earlier; (2) persistent hypotension related to hypovolemia; (3) active ischemia; and (4) at any time it was determined that it was in a patiënt’s best interest to receive a transfusion. Once the active issue was resolved, transfusion was again administered according to the study protocol

Length of follow-up: 30 days

Loss-to-follow-up:

Intervention: 1

Control: 2

Reasons (describe): lost after hospital discharge

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Outcome measures and effect size (include 95%CI and p-value if available):

Mortality (30 days):

Restrictive: 2

Liberal: 1

Myocardinfarct:

Restrictive: 0%

Liberal: 5%

Ischemic event:

Not reported

Infectious event:

Not reported

Clinically significant pulmonary complications:

Restrictive:

Liberal:

Patiënts transfused:

Restrictive: 54%

Liberal: 100%

Units transfused:

Restrictive: 1.6 ± 2.0

Liberal: 2.5 ± 1.3

No. of days in hospital (median):

Restrictive: 10.4 ± 7.2

Liberal: 8.5 ± 5.6

Acute myocardial infarction

Hebert, 1995

Type of study: multicentre, prospective, randomized clinical trial

Setting: tertiary level intensive care unit

Country: Canada

Source of funding: Canadian Red Cross Society, Blood Services, Ottawa, Ontario and the Physician’s Services Incorporated, North York, Ontario

Inclusion criteria: all patiënts admitted to one of five tertiary-level intensive care units between March 1993 and January 1994 were considered elegible; patiënts were expected to stay more than 24 hours, had a haemoglobin value less than or equal to 90 g/L within 72 hours of ICU admission and were considered volume resuscitated or normovolemic by the attending staf

Exclusion criteria: less than 16 years of age, pregnant, unable to receive blood products, active blood loss at the time of enrolment, defined as a 30-gL decrease in haemoglobin in the preceding 12 hours or at least 3 U of packed RBCs during the same period; brain dead or not expected to survive for more than 24 hours, or admitted following routine cardiac surgical interventions

N total at baseline:

Intervention: 33

Control: 36

Important prognostic factors²:

Age ± SD:

I: 58.6 ± 15

C: 59 ± 21

Sex:

I: 42% M

C: 53% M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

Restrictive transfusion strategy:

Haemoglobin levels maintained between 70 and 90 g/L, with a transfusion trigger at 70 to 75 g/L

Describe control (treatment/procedure/test):

Liberal transfusion strategy:

Hemoglobin level maintinaed between 100 and 120 g/L, with a transfusion trigger at 100 to 105 g/L

Length of follow-up: 30 days

Loss-to-follow-up:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Outcome measures and effect size (include 95%CI and p-value if available):

Mortality (30 days):

Restrictive: 24%

Liberal: 25%

Units transfused:

Restrictive: 2.5

Liberal: 4.8

No. of days in ICU (median):

Restrictive: 6 (3-12)

Liberal: 9 (5-12)

No. of days in hospital (median):

Restrictive: 38 (25-62)

Liberal: 31 (13-64)

Hebert, 1999

Type of study: multicentre, prospective, randomized clinical trial

Setting: intensive care unit

Country: Canada

Source of funding: Supported by the Medical Research Council of Canada and by an unrestricted grant from Bayer.

Inclusion criteria: admitted to 1 of 22 tertiary-level and 3 community intensive care units in Canada between November 1994 and November 1997; patiënts who were expected to stay in the intensive care unit more than 24 hours, had a hemoglobin concentration of 9.0 g per deciliter or less within 72 hours after admission to the intensive care unit, and were considered to have euvolemia after initial treatment by attending physicians.

Exclusion criteria: an age of less than 16 years; inability to receive blood products; active blood loss at the time of enrollment; chronic anemia; pregnancy; brain death or imminent death (within 24 hours); a question on the part of attending physicians whether to withhold or withdraw ongoing treatment; and admission after a routine cardiac surgical procedure.

N total at baseline:

Restrictive: 418

Liberal: 420

Important prognostic factors²:

age ± SD:

I: 57.1 ± 18.1

C: 58.1 ± 18.3

Sex:

I: 64% M

C: 61% M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

restrictive strategy:

maintained in the range of 7.0 to 9.0 g per deciliter, with a transfusion given when the hemoglobin concentration fell below 7.0 g per deciliter.

Describe control (treatment/procedure/test):

liberal strategy:

hemoglobin concentrations were maintained in the range of 10.0 to 12.0 g per deciliter, with a threshold for transfusion of 10.0 g per deciliter.

Length of follow-up: 60 days

Loss-to-follow-up:

Intervention: 5

Control: 4

3 additional patiënts were lost at 60 days follow-up

Cross-over:

Intervention: 1%

Control: 2.6%

Outcome measures and effect size (include 95%CI and p-value if available):

Mortality (30 days):

Restrictive: 18.7%

Liberal: 23.3%

Mortality (60 days):

Restrictive: 22.7%

Liberal: 26.5%

Myocardinfarct:

Restrictive: 3 (0.7%)

Liberal: 12 (2.9%)

Cardiac complication:

Restrictive: 55 (13.2%)

Liberal: 88 (21%)

Infectious event:

Restrictive: 42 (10%)

Liberal: 50 (11.9%)

Pulmonary complications:

Restrictive: 106 (25.4%)

Liberal: 122 (29.0%)

Patiënts transfused:

Restrictive: 280

Liberal: 420

Units transfused:

Restrictive: 2.6 ± 4.1

Liberal: 5.6 ± 5.3

No. of days in ICU (median):

Restrictive: 11.0 ± 10.7

Liberal: 11.5 ± 11.3

No. of days in hospital (median):

Restrictive: 34.8 ± 19.5

Liberal: 35.5 ± 19.4

Executive committee , without foreknowledge of treatment-specific outcomes, decided to terminate the study prematurely because of a decrease in enrolment to below 20% of predicted levels over a period of several months

Most common reasons for enrolment were respiratory and cardiac diseases

Cardiac complication included myocardial infarction, pulmonary edema, angina and cardiac arrest

Holst, 2014

Type of study: RCT

Setting: ICU

Country: Denmark, Sweden and Finland

Source of funding: Supported by a grant (09-066938) from the Danish Strategic Research Council and by Copenhagen University Hospital, Rigshospitalet, the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (ACTA Foundation), and Ehrenreich’s Foundation. Dr. Johansson reports receiving grant support from Pharmacosmos; and Dr. Perner, receiving grant support from CSL Behring, Fresenius Kabi, Cosmed, and Bioporto Diagnostics, and lecture fees from LFB.

Inclusion criteria: patiënts 18 years of age or older who were in the ICU, fulfilled the criteria for septic shock,18 and had a blood concentration of haemoglobin of 9 g per deciliter or less as measured by means of valid point-of-care testing

Exclusion criteria: declined transfusion, previous adverse reaction to transfusion, received blood transfusion in ICU, had acute coronary syndrome, had life-threatening bleeding, had acute burn injury, withdrew from active therapy, or were excluded because consent could not be obtained

N total at baseline:

Intervention: 503

Control: 497

Important prognostic factors²:

Age (median):

I: 67

C: 67

Sex:

I: 54% M

C: 52% M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

Lower treshold

Patiënts were given single units of cross-mateched , prestorage leukoreduced red cells suspended in a saline-adenine-glucose-mannitol solution when the blood haemoglobin had decreased to <= 7 g/dL

In the event that a life-threatening bleeding or ischaemia developed while a patiënt was in ICU or patiënt required the use of extracorporal membrane oxygenation, the patiënt could receive a transfusion at a haemoglobin threshold decided by the attending doctor.

Describe control (treatment/procedure/test):

Higher threshold:

Patiënts were given single units of cross-mateched , prestorage leukoreduced red cells suspended in a saline-adenine-glucose-mannitol solution when the blood haemoglobin had decreased to <= 9 g/dL

In the event that a life-threatening bleeding or ischaemia developed while a patiënt was in ICU or patiënt required the use of extracorporal membrane oxygenation, the patiënt could receive a transfusion at a haemoglobin threshold decided by the attending doctor.

Length of follow-up: entire ICU stay with a maximum of 90 days

Discontinued the study:

Intervention: 38

Control: 24

Reasons: withdrawn at patiënt’s or surrogate’s request; withdrawn at a phyisican’s request; withdrew consent for use of data

Protocol temporarily suspended:

Intervention: 29 (5.9%)

Control: 11 (2.2%)

Incomplete outcome data:

Intervention: 14

Control: 7

Reasons (describe): did not wish to be included in follow-up

Protocol violations:

(one or more transfusions given despite being above the assisgned Hb threshold)

Intervention: 45

Control: 16

(transfusion not given despite being below the assisgned Hb threshold on at least one Hb measurement)

Intervention: 42

Control: 104

Outcome measures and effect size (include 95%CI and p-value if available):

Mortality (90 days):

Restrictive: 216 (43%)

Liberal: 223 (45%)

Myocardinfarct:

Restrictive: 13

Liberal: 6

Ischemic event:

Restrictive: 35 (7%)

Liberal: 39 (8%)

Infectious event:

Not reported

Pulmonary complications:

Not reported

TRALI or TACO:

Restrictive: 0

Liberal: 1

Patiënts transfused:

Restrictive: 503-176=327 (65%)

Liberal: 497-6=491 (99%)

Units transfused (median:

Restrictive: 1

Liberal: 4

No. of days in hospital (median):

Not reported

Patiënts in the ICU with septic shock

Ischemic events included: cerebral ischaemia, acute myocardial ischemia, intestinal ischemia, or limb ischemia

Lacroix, 2007

Type of study: RCT

Setting: PICU

Country: Canada

Source of funding: Supported by grants (84300 and 130770) from the Canadian Institutes of Health Research and by grants (3348 and 3568) from the Fonds de la Recherche en Santé du Québec.

Inclusion criteria: Stable, critically ill children between 3 days and 14 years of age who had at least one hemoglobin concentration of 9.5 g per deciliter or less within the first 7 days after admission to the pediatric ICU were eligible for enrollment.

Exclusion criteria: expected to stay <24 hr in ICU, no approval from physician, <3 days or >14 yr of age, unstable hemodynamically,had acute blood loss, weighed <3.0 kg, had cardiovascular problems, were never discharged from neonatal ICU, had hemolytic anemia, enrolled in another study

N total at baseline:

Intervention: 320

Control:317

Important prognostic factors²:

age ± SD:

I: 35.8 ± 46.2

C: 39.6 ± 51.9

Sex:

I: 59% M

C: 60% M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

restrictive

restrictive-strategy group, the haemoglobin threshold for transfusion was set at 7 g per deciliter, with a target range after transfusion of 8.5 to 9.5 g per deciliter.

Describe control (treatment/procedure/test):

Liberal

liberal-strategy group, the threshold was 9.5 g per deciliter, with a target range of 11 to 12 g per deciliter. In both groups, red cells were transfused within 12 hours after the threshold value had been reached.

Length of follow-up: 28 days

Loss-to-follow-up:

11 (2%)

Reason unknown

Protocol violation:

Restrictive: 1

Liberal: 10

Incomplete outcome data:

-

Outcome measures and effect size (include 95%CI and p-value if available):

Mortality (30 days):

Restrictive: 14/320

Liberal: 14/317

Adverse events:

Restrictive: 221

Liberal: 203

Infectious event:

Restrictive: 65/320

Liberal: 79/317

Patiënts transfused:

Restrictive: 146 (46%)

Liberal: 310 (98%)

Units transfused:

Restrictive: 0.9 ± 2.6

Liberal: 1.7 ± 2.1

No. of days in hospital (median):

Restrictive:

Liberal:

Naidech, 2010

Type of study: randomized trial

Setting: intensive care

Country: USA

Source of funding: grants to AMN from the Neurocritical Care Society, supported by Novo-Nordisk (for partial salary support) and from the Northwestern Memorial Foundation for MRI scans and additional PRBC transfusions above usual care.

Inclusion criteria: were SAH within three calendar days of enrollment (before vasospasm and cerebral infarction usually occur), World Federation of Neurologic Surgeons grades two through four at enrollment (patiënts with grade five on admission could be enrolled if they improved to grade four or better) or grade one with thick subarachnoid clot (Columbia CT grading scale 3–4) (13), and aneurysm obliteration imminent or completed.

Exclusion criteria: cerebral infarction on CT before enrollment

N total at baseline:

Restrictive: 23

Liberal: 21

Important prognostic factors²:

Age (median) ± SD:

Restrictive: 59.2 ± 11.9

Liberal: 54.1 ± 14.9

Sex:

Restrictive: 22% M

Liberal: 21%M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

Restrictive strategy

Transfusion at <10 g/dl

If the HGB was 0.1–1 g/dl below goal, then one unit PRBC was given; if >1 g/dl below goal, then two units were given with follow-up after the transfusion. All the PRBC units are leukoreduced at our institution.

Describe control (treatment/procedure/test):

Liberal strategy

Transfusion at <11.5g/dl

If the HGB was 0.1–1 g/dl below goal, then one unit PRBC was given; if >1 g/dl below goal, then two units were given with follow-up after the transfusion. All the PRBC units are leukoreduced at our institution.

Length of follow-up: 3 months

Loss-to-follow-up:

unclear

Incomplete outcome data:

unclear

Outcome measures and effect size (include 95%CI and p-value if available):

Mortality (30 days):

-

Myocardinfarct:

-

Thromboembolic events:

-

Infectious event:

Restrictive: 0

Liberal: 0

Pulmonary complications:

Restrictive: 1

Liberal: 1

Patiënts transfused:

Restrictive: 19/23 (83%)

Liberal: 20/21 (95%)

Units transfused:

Restrictive: 2 (1-3)

Liberal: 3 (2-4)

.

Robertson, 2014

Type of study: randomized trial using a factorial (2 × 2) design

Setting: Neurosurgical intensive care units of two Houston level 1 trauma centers

Country: USA

Source of funding: supported by National Institute of Neurological Disorders and Stroke (grant

#P01-NS38660)

Inclusion criteria: patiënts admitted to the two level 1 trauma centers in

Houston with a closed head injury who were not able to follow commands after resuscitation

and could be enrolled within 6 hours of injury

Exclusion criteria: Glasgow Coma

Score (GCS) of 3 with fixed and dilated pupils, penetrating trauma, pregnancy, lifethreatening

systemic injuries, and severe pre-existing disease

N total at baseline:

Intervention: 87

Control: 94

Important prognostic factors²:

age (median):

I:30 (22-40)

C: 28 (21-48)

Sex:

I: 85.7% M

C: 85.9% M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

7 g/dL

Describe control (treatment/procedure/test):

10 g/dL

Length of follow-up: 6 months

Loss-to-follow-up:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

Outcome measures and effect size (include 95%CI and p-value if available):

Mortality (30 days):

Restrictive: 14

Liberal: 17

Myocardinfarct:

Not reported

Thromboembolic events:

Restrictive: 8

Liberal: 22

Infectious event:

Restrictive: 27

Liberal: 36

Pulmonary complications:

Not reported

Patiënts transfused:

Restrictive: 52 (52.5%)

Liberal: 73 (72.3%)

Units transfused:

Restrictive: 4.1 (1-22)

Liberal: 7.1 (1-21)

No. of days in hospital (median):

Not reported

Traumatic brain injury

Patiënts received Epo (Epogen, Amgen, Inc.,

Thousand Oaks, CA) 500 IU/kg or an equal volume of saline intravenous bolus infusion

over two minutes for each dose of the study drug.

During the acute post-injury recovery period (until intracranial pressure monitoring and

ventilatory support were no longer required), the assigned hemoglobin threshold was

maintained with transfusion of leukoreduced PRBCs

Walsh, 2013

Type of study: RCT

Setting: Intensive care: critically ill requiring prolonged ventilation

Country: Scotland

Source of funding: Supported, in part, by the Chief Scientists Office, Scotland (CZB/4/698); the Scottish National Blood Transfusion Service, the NHS Lothian Academic Health Science Centre; and the Transfusion Medicine Education and Research Foundation.

Inclusion criteria: (1): had already required mechanical ventilation via an endotracheal tube or tracheostomy tube for ≥ 96 hours (2); were expected to require ≥ 24 hours of further mechanical ventilation when assessed (3); were aged ≥ 55 years old(4); and had a Hb value of ≤ 90g/L at the time of assessment

Exclusion criteria: patiënts with active bleeding at the time of screening, traumatic brain injury and/or intracranial hemorrhage, not expected to survive for 48 hours when assessed, objection to receiving RBC transfusions, concurrent treatment with erythropoietin or similar agents, follow-up that was not feasible, and enrolment in another trial with similar endpoints

N total at baseline:

Intervention: 51

Control: 49

Important prognostic factors²:

Mean age:

I: 67 (56-80)

C: 69 (55-83)

Sex:

I: 71% M

C: 49% M

Groups comparable at baseline? yes

Describe intervention (treatment/procedure/test):

“restrictive transfusion strategy group” received single unit RBC transfusions with a transfusion trigger of less than or equal to 70 g/L and a target Hb concentration of 71–90 g/L during the intervention period.

Describe control (treatment/procedure/test):

“liberal RBC transfusion group” received single-unit RBC transfusions with a transfusion trigger of less than or equal to 90 g/L and a target of 91– 110 g/L during intervention.

Length of follow-up: up to 60 days

Loss-to-follow-up:

-

Incomplete outcome data:

Data were complete

Outcome measures and effect size (include 95%CI and p-value if available):

Mortality (30 days):

Restrictive: 12/51

Liberal: 16/49

Mortality (60 days):

Restrictive: 14/51

Liberal: 22/49

Myocardinfarct:

Not reported

Ischemic event:

Not reported

Infectious event:

Not reported

Clinically significant pulmonary complications:

Restrictive:

Liberal:

Patiënts transfused:

Restrictive: 78%

Liberal: 100%

Units transfused:

Restrictive: 3

Liberal: 4

No. of days in hospital (median):

Restrictive: 34 (3-159)

Liberal: 31 (1-120)

anaemic older critically ill patiënts requiring prolonged mechanical ventilation

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Carson, 2013

Using an automated telephone system, we implemented a permuted block randomization process stratified by clinical site and clinical diagnosis (acute coronary syndrome or stable coronary artery disease).

likely

likely

likely

unlikely

unlikely

unlikely

unlikely

Cholette, 2011

Block randomization was used (block size 8) was used to randomize subjects to either the restrictive or liberal transfusion strategy

likely

unclear

unclear

unclear

unlikely

unlikely

unlikely

Cooper, 2011

Patiënts were randomly assigned in a 1:1 ratio to 1 of 2 treatment groups by the coordinating center

using consecutively numbered opaque envelopes

unlikely

unclear

likely

likely

unlikely

unlikely

unlikely

Hebert, 1995

Patiënts were assigned to one of two treatment groups by consecutive allocation from a random listing stratified by center and disease severity.

unlikely

unclear

unclear

unclear

unlikely

unlikely

unlikely

Hebert, 1999

Sealed, opaque envelopes arranged in a computer-generated

random order were prepared by the data-coordinating center and

distributed to each participating institution, where they were

opened sequentially to determine the patiënts’ treatment assignments.

unlikely

unclear

unlikely

unlikely

unlikely

unlikely

unlikely

Holst, 2014

with the use of a centralized computergenerated

assignment sequence, with stratification

according to study site and the presence or absence

of active hematologic cancer

unlikely

unclear

unlikely

unlikely

unlikely

unlikely

unlikely

Lacroix, 2007

Randomization was centralized, with assignment

data posted on the Internet. Patiënts were assigned

to the study groups in blocks of 2 or 4 that were

randomly distributed and stratified according to

center and three age groups

unlikely

unclear

unclear

unlikely

unlikely

unlikely

unlikely

Naidech, 2010

Opaque envelopes were randomly prepared in blocks of ten, and the next envelope in sequence was opened upon obtaining written consent.

unlikely

unlikely

not possible

unlikley

unlikely

unlikely

unlikely

Robertson, 2014

A randomization list, stratified by site and using one randomization event to both factors in

blocks of 4, was prepared by the study statisticians and kept in each hospital’s research

pharmacy. When a new patiënt was enrolled, the research pharmacist prepared the study

drug based on the patiënt’s weight and treatment assignment from the randomization list and

informed the investigators of the transfusion threshold assignment.

unlikely

unclear

unclear

unlikely

unlikely

unlikely

unlikely

Walsh, 2013

Patiënts were randomized 1:1

to each group. Minimization by center and the presence of IHD,

including a random element, was used. Telephone randomization

by research staff was undertaken within the ICUs using the

Aberdeen Health Services Research Unit service to ensure allocation

concealment prior to randomization.

unlikely

unlikely

unclear

unclear

unlikely

unlikely

unlikely

Auteur en jaartal

Redenen van exclusie

Adams, 2009

Critical appraisal van Lacroix et al., 2007, geen origineel onderzoek

British Journal Haematology guideline, 2013

Geen formeel systematisch literatuuronderzoek uitgevoerd

Bergamin, 2014

Congres abstract

Blair, 1986

Severe upper gastrointestinal haemorrhage, wordt uitgewerkt bij acute bloedingen (main outcome rebleeding)

Carless, 2010

Review met bredere doelgroep dan alleen IC, search t/m augustus 2009

Carson, 2016

AABB guideline. Geïncludeerde studies op IC hebben vooral betrekking op gebruik van ‘fresh blood’

Carson, 2016b

Cochrane, 31 trials, bredere doelgroep, search t/m mei 2016

Carson, 2013b

Review met search t/m feb 2011, summary van Cochrane (Carson, 2012) en JAMA (Carson, 2013)

Carson 2012, b

AABB guideline, search t/m feb 2011

Carson, 2012

Cochrane, 19 trials, search t/m feb 2011

Carson, 2002

Systematic review, search t/m 2000

DeAlmeida

IC in tertiary care oncology center

Desjardins, 2012

Systematic review neurocritically ill patiënts, search t/m januari 2011 en neemt ook retrospectieve cohort studies mee

Duana, 2008

Retrospective review of patiënts with isolated head trauma

Dupuis, 2017

Patiënts with sepsis in ICU systematic review: 1 RCT (Holst) en 12 cohort studies, search t/m maart 2015, smallere doelgroep dan PICO

English, 2016

Protocol

Fominsky, 2015

Meta-analyse, search t/m maart 2015

George, 2008

Retrospective study in isolated traumatic brain injury

Goodnough, 2014

Retrospective comparison of clinical decision support

Gu, 2015

Alleen abstract congres

Hardy, 2004

Comprehensive review

Hayek, 2016

Alleen abstract congres

Hebert, 2001

Uitkomst mechanical ventilation, niet conform PICO

Hill, 2002

Systematic review, search t/m 2004

Hogshire, 2013

Narrative review

Holst, 2016

PhD thesis, verwijst naar publicatie van trial resultaten uit 2014, geen origineel onderzoek

Hovaguimian, 2016

Syst review en meta-analyse, search t/m nov 2015, 31 trials:

3 groepen: cardiac/vascular procedures; elderly orthopaedic patiënts; critically ill

Karam, 2010

Critcally ill IC kinderen met sepsis, subgroup Lacroix et al., 2007

Leal-Noval, 2008

Narrative review

Manchal, 2007

Cohort study

McIntyre, 1999

Subgroup analyses of RCT, TRICC trial

McIntyre, 2004

Subgroup analyses of RCT, TRICC trial, nu voor resuscitated critically ill

Melchor, 2016

Syst review IC en acute coronary syndrome, search t/m December 2014, 6 RCTs:

Mirski, 2015

Narrative review

Murphy, 2015

Uitgewerkt bij cardiac surgery patiënten

Napolitano, 2009

Clinical practice guideline, search t/m juli 2008. Doelgroep trauma en ICU

Napolitano, 2004

Narrative review

Parker, 2014

Narrative review critically ill children

Pinheiroalmeida, 2015

patiënten met maagkanker opgenomen in een tertiary care oncology unit die een grote abdominale operatie ondergingen en daarna IC opname nodig hadden

Pleyer, 2015

Acute myeloid leukemia, erg specifieke subgroep patiënten

Rohde, 2014

Syst review search t/m januari 2014, doelgroep hospitalized patiënts, niet specifiek IC

Roubinian, 2014

Cohort study

Roubinian, 2015

Commentaar

Rouette, 2010

PICU, postsurgical

Rygard, 2016

Excluderen want subgroup Holst

Salpeter, 2014

Syst review en meta-analyse, search t/m april 2013 3 trials

Spahn, 2015

Narrative review

Spiess, 1998

Niet de juiste uitkomsten gerapporteerd

Stanworth, 2016

Powerpoint

Szpila, 2015

Retrospective historical control analysis

Villanueva, 2013

Acute upper gastrointestinal bleeding

Willems, 2010

Subgroep analyse van Tripicu study, Lacroix et al., 2007