Reducing bed rest time from five to three hours does not increase complications after cardiac catheterization: the THREE CATH Trial 1

Abstract Objective: to compare the incidence of vascular complications in patients undergoing transfemoral cardiac catheterization with a 6F introducer sheath followed by 3-hour versus 5-hour rest. Methods: randomized clinical trial. Subjects in the intervention group (IG) ambulated 3 hours after sheath removal, versus 5 hours in the control group (CG). All patients remained in the catheterization laboratory for 5 hours and were assessed hourly, and were contacted 24, 48, and 72 h after hospital discharge. Results: the sample comprised 367 patients in the IG and 363 in the GC. During cath lab stay, hematoma was the most common complication in both groups, occurring in 12 (3%) IG and 13 (4%) CG subjects (P=0.87). Bleeding occurred in 4 (1%) IG and 6 (2%) CG subjects (P=0.51), and vasovagal reaction in 5 (1.4%) IG and 4 (1.1%) CG subjects (P=0.75). At 24-h, 48-h, and 72-h bruising was the most commonly reported complication in both groups. None of the comparisons revealed any significant between-group differences. Conclusion: the results of this trial show that reducing bed rest time to 3 hours after elective cardiac catheterization is safe and does not increase complications as compared with a 5-hour rest. ClinicalTrials.gov Identifier: NCT-01740856


Introduction
The rate of complications after femoral artery puncture for coronary angiography or diagnostic cardiac catheterization ranges from 1.5% to 3.7%, with vascular complications having the highest incidence (1) . Particularly in the first 6 to 12 hours after a transfemoral procedure, care of the insertion site is a determining factor in the occurrence or mitigation of these complications and a reminder of the constant vigilance that these patients require (2) .
Despite rapid advancement in techniques, catheters, contrast agents, and implantable devices, post-catheterization nursing care has not evolved at a similar pace, and remains classically based on bed rest, which may last 2 hours (3) to 24 hours (4) . A recent meta-analysis of 20 studies and 4,019 patients found that a bed rest duration of 2-3 hours after transfemoral catheterization is safe, has no effect on the incidence of vascular complications, and may reduce back pain and discomfort (5) .
Although the literature suggests that early mobilization is safe after diagnostic catheterization, studies are unclear as to the setting of this intervention. Furthermore, the only study on shorter bed rest conducted in Brazil was carried out at a private clinic (6) ; therefore, its results cannot be extrapolated to a large, high-complexity teaching hospital, which was the proposed setting for the present study. In addition, at the facility where the present study was carried out, transfemoral diagnostic catheterization is performed by multiple operators, ranging from experienced physicians to residents in training, and is followed by a standard 5-hour rest period. This study is relevant insofar as it reports the results of an intervention that could be incorporated immediately into the clinical practice of a variety of health facilities with similar profiles.
Within this context, the present randomized controlled trial (RCT) was designed to test the hypothesis that reducing the duration of bed rest to 3 hours in the intervention group (IG) from 5

Participants
The study sample comprised adult outpatients who underwent elective transfemoral diagnostic cardiac catheterization with a 6F introducer sheath. The exclusion criteria were any restrictions to ambulation, use of coumarin anticoagulants, body mass index (BMI) > 35kg/m 2 , hypertension with a systolic blood pressure (SBP) > 180mmHg or diastolic blood pressure (DBP) > 110mmHg at the end of the procedure, and a history of uncontrolled bleeding.
The study protocol was approved by the Research Ethics Committee of the facility where the trial was carried out. All patients were informed of the objectives of the study and were only included after having read and signed an informed consent form.

Study protocol and group allocation
Patients who met the inclusion criteria and were considered eligible were invited to take part in the study. At the end of the procedure, patients were taken to the observation unit (OU). Removal of the introducer sheath with hemostasis valve and manual (digital) compression of the insertion site for 15 minutes were performed by the nursing staff in both groups. Patients were instructed to refrain from moving the affected leg.
After the second hour of bed rest, the nursing team

Intervention group
Patients randomly allocated to the intervention group

Control group
Participants randomly allocated to the CG remained in bed, in the supine position, for 4 hours after completion of the manual compression period. After this period, patients remained with the head of bed elevated at 45 degrees for 60 minutes and were made to ambulate around the cath lab for 10 minutes. Patients were then discharged and walked out of the hospital.
Both groups received post-procedural care guidance and were monitored hourly by the nursing staff. Patients were notified that they would be contacted by telephone 24, 48, and 72 hours after hospital discharge, and were given an instruction sheet containing descriptions and illustrative images of bleeding, hematoma, bruising, and pseudoaneurysm, as well as a ruler, with which they could measure any visible complications at the puncture site.

Primary outcome
The primary outcome was occurrence of complications (hematoma, bleeding, and pseudoaneurysm), defined as follows: 1) Hematomas at the arterial puncture site, classified in accordance with the American College of Cardiology definition (large, > 10 cm; small, < 10 cm) (7) ; 2) Major bleeding, as defined for the Evaluating the

Implementation of the ACC/AHA Guidelines (CRUSADE)
bleeding score trial: documented retroperitoneal bleeding (not requiring surgical correction) or any red blood cell transfusion with witnessed bleed (8) . Patients who developed hemodynamic instability, defined as uncontrolled hypertension or hypotension, tachycardia or bradycardia, or desaturation from baseline, were also considered to have major bleeding. If no hemodynamic instability occurred, bleeding was considered minor (8) ; 3) Any of the following vascular complications requiring surgical correction: retroperitoneal bleeding, pseudoaneurysm, or development of arteriovenous fistula (9) .

Secondary outcomes
The secondary outcomes of interest were vasovagal response to sheath withdrawal, bruising, association/comparison between current medications and comorbidities, and association/comparison between sex and events during OU stay and at 24-, 48-, and 72hour follow-up.

Sample size calculation
The sample size calculation was based on the assumption that the proportion of events would not be higher in IG than in CG participants. Considering a negligible difference between the intervention and control group, a 2% rate of events, and a 20% attrition rate, the minimum sample size was estimated at 714 patients for an alpha level of 0.05 and 80% statistical power (9) . Overall, 48 participants (6.6%) were lost to follow-up, for a final sample size of 730.

Randomization
The confidence intervals were calculated to assess the effect size of the intervention. Two-tailed P-values < 0.05 were considered significant.

Discussion
This RCT was the first study conducted in a In both groups, the most common vascular complication during OU stay was puncture site hematoma (no significant between-group difference), followed by bleeding and vasovagal response. However, at 24-hour, 48-hour, and 72-hour telephone follow-up, it was the complication least reported by patients. The literature suggests that the incidence of arterial access-related hematoma ranges from 0.1 to 9%, with hematomas graded as large if > 10cm or small if < 10cm (10) .
In a meta-analysis of 20 studies and 4,019 patients that sought to assess the effects of bed rest duration after transfemoral cardiac catheterization, the incidence of hematoma was approximately 7.6% (5) . It should be noted that the included studies employed different introducer sheath sizes, ranging from 4F to 9F. Some authors have reported that female patients are more prone to developing hematoma (6,(11)(12) . Characteristics such as body surface area, vessel size, increased sensitivity to anticoagulants and antiplatelet agents, or hormonal differences may explain this predilection (12)(13) .
In the present RCT, regardless of group allocation, women reported significantly more events than men at 24-hour, 48-hour, and 72-hour telephone follow-up, which corroborates the existing literature.  (1) . The malaise caused by prolonged supine positioning and immobility, compounded by difficulty urinating, pelvic discomfort, and anxiety, are predictors of vasovagal response during sheath withdrawal (15) .
Within this context, shortening the duration of bed rest may reduce this complication.
In both groups, bruising at the insertion site was the most commonly reported complication at telephone follow-up, followed by pain and hematoma.
In a study (3)  after discharge. Thus, the authors concluded that early ambulation was safe in their patient population (3) .
Patients who have undergone cardiac catheterization experience restricted mobility due to arterial puncture of the catheterized limb. Back pain and discomfort secondary to immobilization are often recorded by cath lab nurses, and are the most common complaints of patients in this setting (13) . Nursing care should focus on patients' difficulties and judicious monitoring. Studies of patients undergoing interventional radiology procedures have demonstrated that duration of bed rest is associated with discomfort (2,6,(12)(13)16) . Indeed, discomfort and impatience have been observed in patients during the recovery period, both while in hospital and after discharge to home. Pain and discomfort was the second most common complication (complaint) at 24-hour, 48hour, and 72-hour follow-up. A Swedish study (11) that assessed this complication up to 3 days post-procedure found that shortening the immobilization period had beneficial effects on patient comfort and satisfaction.
Prolonged rest can cause muscle weakness and fatigue due to constant pressure over the same muscle groups, and fatigue can, in turn, lead to muscle spasms and back pain. These authors also reported that reducing the duration of bed rest can reduce back pain and discomfort without increasing vascular complications.
In this setting, early ambulation is a particularly relevant additional strategy to improve patient comfort after cardiac catheterization procedures. In the present sample, antiplatelet therapy and presence of comorbidities were not associated with increased risk of complications.
In short, the strategy tested in this trial -i.e., reducing duration of bed rest after diagnostic cardiac catheterization to 3 hours -proved feasible and safe.