Red Blood Cell Transfusion

Both studies used the same protocol to ascertain outcomes. Patients were followed for the intended treatment period and assessed at fixed intervals that were identical in the two treatment groups
[8 (link),9 (link)]. The prespecified efficacy outcome was symptomatic recurrent VTE, i.e. the composite of fatal or nonfatal PE or DVT
[8 (link),9 (link)]. The prespecified principal safety outcome was clinically relevant bleeding, defined as the composite of major and nonmajor clinically relevant bleeding, as described previously
[8 (link),9 (link)]. Bleeding was defined as major if it was clinically overt and associated with a decrease in hemoglobin level of ≥2.0 g/dl; if bleeding led to the transfusion of ≥2 units of red cells; or if bleeding was intracranial or retroperitoneal, occurred in another critical site, or contributed to death. Nonmajor clinically relevant bleeding was defined as overt bleeding that did not meet the criteria for major bleeding but was associated with medical intervention, unscheduled contact with a physician, interruption or discontinuation of study drug, or discomfort or impairment of activities of daily life. We also prespecified to analyze net clinical benefit, which was defined as the composite of the primary efficacy outcome and major bleeding.

This single center, prospective observational sequential-group study was conducted at Thorax Centrum Twente (Medisch Spectrum Twente, Enschede, The Netherlands), a tertiary non-academic teaching hospital. Consecutive adult patients undergoing non-salvage cardiac surgery were included. Patients were excluded with a Katz Index of Independence in Activities of Daily Living ≤ 2 before surgery (i.e. all patients included were preoperatively independent in daily life mobilization) [21 (link)] and patients with an intensive care unit (ICU) stay longer than 72 h were also excluded from analysis.
All patients were admitted to the ICU after surgery. An A1 paper size (84 × 59 cm) mobilization poster for each patient room was developed (Fig. 1) based on preliminary external work with a smaller A4 paper size leaflet [22 (link)].Fig. 1

A Design of mobilization poster to promote early mobilization at cardio-thoracic surgery ward attached to every patient room; B Poster situated in patient room in original language (Dutch)

The “Moving is Improving!” practice improvement initiative recruited from 03 to 20 October 2016 as UCG, and from 31 October 2016 to 22 November 2016 for the poster mobilization group (PMG). This practice improvement was initiated when nurses and physiotherapists observed that patients were not motivated for early mobilization. A best practice unit leadership program was started with the underlying study.
7 dedicated physical therapists trained for cardio-thoracic physiotherapy practice participated in the study. Physical therapists were trained in ACSM and TCT classification and a pocket card was handed out for daily use. Nurses and surgical staff were also educated on the importance of early mobilization. One physical therapy intern was added to the team in the PMG, and received similar training. A physiotherapist noted down patient-reported ACSM score daily at each patient room, and was collected after discharge. After interim analysis, the mobilization poster (Translated from Dutch to English, Fig. 1) was implemented as new standard care in the cardio-thoracic surgery ward and patients were also included from 10 September 2017 to 26 March 2018 (PMG).
ACSM score (see Table 1 for definitions) was used to compare UCG to PMG during postoperative hospital stay. No other changes than the poster were implemented during the study.
Change in in-hospital ACSM score and a more detailed Thorax Centrum Twente score (TCT) were defined as primary endpoints. Secondary endpoints included ICU length of stay, surgical ward stay and 30-, 120-day and overall survival. Follow-up on mortality was 100% and ended 1 February 2021. Baseline characteristics were determined based on EuroSCORE II definitions [23 (link)]. Rethoracotomy within 30 days, red blood cell transfusions, and rhythm problems were defined according to Netherlands Heart Registry definitions [24 ]. Temporary pacemaker leads were removed at postoperative day 2 to 5, depending on the type of surgery and underlying rhythm. Having a temporary pacemaker lead was no constraint for mobilization.
A 3 weeks interval of cardio-thoracic surgery determined UCG study size. A consecutive 3 weeks interval determined PMG size and was followed by 6 months use of the poster as new standard care (PMG).
The investigation conforms with the principles outlined in the Declaration of Helsinki [25 (link)]. This study was exempted from the Medical Research Involving Human Subjects Act by the Medical Ethics Committee Twente (METC Twente: K16-85) and was approved by the local institutional review board. Patients therefore did not sign informed consent.

The following baseline measurements were analysed: age, sex, Body Mass Index (BMI), American Society of Anaesthesiology Physical Score (ASA PS), quantity of preoperative long-term agents taken by the patient, polypharmacy defined as more than five preoperative long-term agents, Anti-cholinergic Drug Scale (ADS) of the long-term agents, type of surgery, incision-suture time, applied volume of placebo or dexmedetomidine.
Complementary to the baseline characteristics, opioid, anaesthetic, and red blood cell transfusion requirements were recorded from the intraoperative data as potential influencing factors on cholinesterase activities.

PEA was performed from median sternotomy, the patient was cooled to 18°C to 20°C using cardiopulmonary bypass (CBP), and bilateral PEA was performed under deep hypothermic circulatory arrest. Unfractionated heparin (Leo Pharmaceutical Products, Denmark) was used for intraoperative anticoagulation monitored by activated clotting time (ACT) (target > 480 s Kaolin-ACT, Medtronic.Inc. ACTII, Minneapolis, MN, USA). Before the initiation of CBP, 500 to 1000 ml of blood was harvested, and returned to the patient after weaning off CPB, heparin reversal by protamine sulfate, and decannulation. During CPB to maintain patients’ volume status and to minimize the use of crystalloids (plasmalyte 50 mg/ml, Baxter) and possible volume overload autologous blood transfusion (cell saver), allogenic red blood cell (RBC) transfusions (Hb < 60 g/l), 2 to 6 units of solvent-detergent treated standardized plasma (Octaplas®, Octapharma AG, Lachen, Switzerland) or albumin 20% were used. Tranexamic acid was used 30 mg/kg intravenously before the surgical incision and again 15 mg/kg every 2 h for the duration of CPB. ACT was controlled every 20 min on CPB and 3 min after each heparin bolus. After CPB, administration of protamine and harvested blood infusion, coagulation status was controlled (heparinase-ACT, complete blood count, APTT, PT, fibrinogen, AT and D-dimer). Postoperatively in the operation room allogenic RBC were transfused if Hb < 90 g/l or Hct < 30%. The threshold for platelet transfusion was the platelet count <100 ×10⁹/l and for standardized plasma, Octaplas®, PT < 30%.