Jan Hofland

Intraoperative High-Dose Dexamethasone for Cardiac Surgery: A Randomized Controlled Trial

CONTEXT Prophylactic corticosteroids are often administered during cardiac surgery to attenuate the inflammatory response to cardiopulmonary bypass and surgical trauma; however, evidence that routine corticosteroid use can prevent major adverse events is lacking. OBJECTIVE To quantify the effect of intraoperative high-dose dexamethasone on the incidence of major adverse events in patients undergoing cardiac surgery. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized, double-blind, placebo-controlled trial of 4494 patients aged 18 years or older undergoing cardiac surgery with cardiopulmonary bypass at 8 cardiac surgical centers in The Netherlands enrolled between April 13, 2006, and November 23, 2011. INTERVENTION Patients were randomly assigned to receive a single intraoperative dose of 1 mg/kg dexamethasone (n = 2239) or placebo (n = 2255). MAIN OUTCOME MEASURES A composite of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization. RESULTS Of the 4494 patients who underwent randomization, 4482 (99.7%) could be evaluated for the primary outcome. A total of 157 patients (7.0%) in the dexamethasone group and 191 patients (8.5%) in the placebo group reached the primary study end point (relative risk, 0.83; 95% CI, 0.67-1.01; absolute risk reduction, -1.5%; 95% CI, -3.0% to 0.1%; P = .07). Dexamethasone was associated with reductions in postoperative infection, duration of postoperative mechanical ventilation, and lengths of intensive care unit and hospital stays. In contrast, dexamethasone was associated with higher postoperative glucose levels. CONCLUSION In our trial of adults undergoing cardiac surgery, the use of intraoperative dexamethasone did not reduce the 30-day incidence of major adverse events compared with placebo. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00293592.

Perioperative strategy in colonic surgery; LAparoscopy and/or FAst track multimodal management versus standard care (LAFA trial)

BackgroundRecent developments in large bowel surgery are the introduction of laparoscopic surgery and the implementation of multimodal fast track recovery programs. Both focus on a faster recovery and shorter hospital stay.The randomized controlled multicenter LAFA-trial (LAparoscopy and/or FAst track multimodal management versus standard care) was conceived to determine whether laparoscopic surgery, fast track perioperative care or a combination of both is to be preferred over open surgery with standard care in patients having segmental colectomy for malignant disease.Methods/designThe LAFA-trial is a double blinded, multicenter trial with a 2 × 2 balanced factorial design. Patients eligible for segmental colectomy for malignant colorectal disease i.e. right and left colectomy and anterior resection will be randomized to either open or laparoscopic colectomy, and to either standard care or the fast track program. This factorial design produces four treatment groups; open colectomy with standard care (a), open colectomy with fast track program (b), laparoscopic colectomy with standard care (c), and laparoscopic surgery with fast track program (d). Primary outcome parameter is postoperative hospital length of stay including readmission within 30 days. Secondary outcome parameters are quality of life two and four weeks after surgery, overall hospital costs, morbidity, patient satisfaction and readmission rate.Based on a mean postoperative hospital stay of 9 +/- 2.5 days a group size of 400 patients (100 each arm) can reliably detect a minimum difference of 1 day between the four arms (alfa = 0.95, beta = 0.8). With 100 patients in each arm a difference of 10% in subscales of the Short Form 36 (SF-36) questionnaire and social functioning can be detected.DiscussionThe LAFA-trial is a randomized controlled multicenter trial that will provide evidence on the merits of fast track perioperative care and laparoscopic colorectal surgery in patients having segmental colectomy for malignant disease.

Impaired sublingual microvascular perfusion during surgery with cardiopulmonary bypass: a pilot study.

OBJECTIVE Complications after cardiac surgery may involve multiple organ failure, which carries a high mortality. Development of multiple organ failure may be related to impaired microcirculatory perfusion as a result of systemic inflammation. Microcirculatory blood flow alterations have been associated with impaired outcome. We investigated whether these alterations occurred before, during, and after coronary artery bypass grafting. METHODS We observed 25 consecutive patients who underwent elective coronary artery bypass grafting with cardiopulmonary bypass. The sublingual microcirculation was investigated using side-stream dark-field imaging. Side-stream dark-field imaging was performed before (baseline), during, and after surgery. Microvascular blood flow was estimated with a semiquantitative microvascular flow index in small, medium, and large microvessels. Changes in microvascular flow were tested with Wilcoxon signed rank test. RESULTS Median microvascular flow index of medium blood vessels decreased after starting cardiopulmonary bypass relative to that after anesthetic induction (2.6, interquartile range 1.6-3.0, vs 3.0, interquartile range 2.8-3.0, P = .02). There was a trend toward decreased microvascular flow index of small and large vessels relative to baseline (P = .08 and P = .05, respectively). Decreases in microvascular flow index occurred irrespective of changes in systemic blood pressure. After each patients return to the intensive care unit, microvascular flow index increased and normalized in all microvessels. CONCLUSION For the first time, sublingual microvascular blood flow alterations have been observed during cardiopulmonary bypass-assisted coronary artery bypass grafting.

Alveolar recruitment strategy and PEEP improve oxygenation, dynamic compliance of respiratory system and end-expiratory lung volume in pediatric patients undergoing cardiac surgery for congenital heart disease

Objective:  Optimizing alveolar recruitment by alveolar recruitment strategy (ARS) and maintaining lung volume with adequate positive end‐expiratory pressure (PEEP) allow preventing ventilator‐induced lung injury (VILI). Knowing that PEEP has its most beneficial effects when dynamic compliance of respiratory system (Crs) is maximized, we hypothesize that the use of 8 cm H2O PEEP with ARS results in an increase in Crs and end‐expiratory lung volume (EELV) compared to 8 cm H2O PEEP without ARS and to zero PEEP in pediatric patients undergoing cardiac surgery for congenital heart disease.

Usefulness of Intraoperative Real-Time 3D Transesophageal Echocardiography in Cardiac Surgery

Abstract  Background: Recent advances in three‐dimensional (3D) echocardiography allow to obtain real‐time 3D transesophageal (RT3DTEE) images intraoperatively. Methods: Preoperative transthoral echocardiography (TTE) revealed: hypertrophic ventricular septum (TTE:19.3 mm), systolic anterior motion (SAM) not causing obstruction and malcoaptation of the anterior mitral valve leaflet (AMVL), and posterior mitral valve leaflet (PMVL) with severe mitral regurgitation. Results: Intraoperative TEE with a x7‐2t MATRIX‐array transducer (Philips, Andover, MA, USA) with a transducer frequency of x7–2 t mHz, connected to a iE33 (Philips), shows us that the main mechanism and site of regurgitation was an AMVL cleft. We also measured a 24.3‐mm thickness of the ventricular septum and analyzing the 3D full volume acquisition revealed that there was no SAM. Conclusion: Intraoperative RT3DTEE permitted comprehensive 3D viewing of the mitral valve revealing the mechanism of mitral valve regurgitation, SAM, and the exact width of the hypertrophic ventricular septum.

Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac Surgery

Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT, as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19 to 0.96). In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR<15 ml/min per 1.73 m(2). In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD.

Low molecular starch versus gelatin plasma expander during CPB: does it make a difference?

Background: Non-protein plasma expanders carry a risk of potentially severe allergic reactions. As prime for cardiopulmonary bypass, we routinely use a gelatin plasma expander. Plasma expanding during anesthesia is achieved with high molecular starch (200/0.5 kDalton) in combination with Ringer Lactate solution (RL) and in the Intensive Care Unit (ICU) with a low molecular starch (130/0.4 kDalton). We evaluated the feasibility of low molecular starch in combination with RL (group LMSRL) versus gelatin plasma expanding (group GPE) for priming CPB circuits in patients undergoing cardiac surgery in a randomized prospective trial. Methods: One hundred and eighty adults who underwent primary valve or coronary artery bypass graft (CABG) surgery were equally stratified into 3 series of 60 patients with the routinely used oxygenators; Capiox RX-25, CML Duo and Quadrox-D. Then they were randomised by drawing lots and allocated into the LMSRL or GPE groups. We compared hematocrit, hemoglobin, platelet count, activated clotting time (ACT), lactate and colloid osmotic pressure (COP), blood loss, transfusion need, urine production and ICU stay. In addition, we monitored the average trans-oxygenator fluid resistance (AFR) for each type of oxygenator. Results: The COP is significantly lower in the LMSRL group (20 mmHg ± 0.2 versus 18 mmHg ± 0.2, p < 0.0001); as was the total use of plasma expanders (3846ml ± 98 versus 3059ml ± 77, p < 0.001). All other parameters were not significantly different. When comparing the observed AFR for the three types of oxygenators, a lower AFR in the LMSRL group (p < 0.02) was noted for the Capiox RX-25®. Conclusions: This study shows a lower need for plasma expanders in patients who receive only starch plasma expanders. Further, we noted a lower COP in the LMSRL group, but since the mean COP was >17 ± 0.2 mmHg, this cannot be considered of clinical importance. In conclusion, our study result supports the use of low molecular starch as a good alternative choice for priming CPB. Perfusion (2007) 22, 333—337.

Dexamethasone for the prevention of postoperative atrial fibrillation

BACKGROUND Postoperative atrial fibrillation (AF) is a common complication after cardiac surgery. Inflammation is believed to play a pivotal role in the etiology of postoperative AF. There is a suggestion from small studies that perioperative treatment with corticosteroids may reduce postoperative AF. The DExamethasone for Cardiac Surgery (DECS) study was a large randomized trial showing no protective effect of dexamethasone on major adverse events. The aim of this study was to investigate the effect of dexamethasone treatment on the occurrence of AF after cardiac surgery. METHODS The DECS study compared intra-operative dexamethasone (1mg/kg) or placebo treatment in 4494 adult patients undergoing cardiac surgery. AF was defined by the occurrence of any reported AF within 30days after surgery. We also performed an in-depth analysis of a subset of 1565 patients on new-onset AF. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated. RESULTS The incidence of any AF in the main study of 4494 patients was 33.1% in the dexamethasone and 35.2% in the placebo group (RR 0.94, 95% CI: 0.87-1.02, p=0.14). In the substudy of 1565 patients, the incidence of new-onset AF was 33.0% vs. 35.5% (RR 0.93, 95% CI: 0.81-1.07, p=0.31), respectively. There was no protective effect of dexamethasone across clinically important patient subgroups. CONCLUSION Intraoperative administration of dexamethasone had no protective effect on the occurrence of any or new-onset atrial fibrillation after cardiac surgery. Therefore, the use of dexamethasone for the reduction of postoperative AF should not be recommended.

Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial)

BackgroundPre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC). Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass graft surgery (CABG), affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome.Methods/designThis study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1) control, 2) remote ischemic preconditioning, 3) remote ischemic postconditioning, or 4) remote ischemic pre- and postconditioning. Remote conditioning is applied at the arm by 3 cycles of 5 minutes of ischemia and reperfusion. Primary endpoint is the incidence AF in the first 72 hours after surgery, detected using a Holter-monitor. Secondary endpoints include length-of-stay on the intensive care unit and in-hospital, and the occurrence of major adverse cardiovascular events at 30 days, 3 months and 1 year.Based on an expected incidence in the control group of 27%, 195 patients per group are needed to detect with 80% power a reduction by 45% following either pre- or postconditioning, while allowing for a 10% dropout and at an alpha of 0.05. With the combined intervention expected to be stronger, we need 75 patients in this group to detect a reduction in incidence of AF of 60%.DiscussionThe RICO-trial (the effect of Remote Ischemic Conditioning on atrial fibrillation and Outcome) is a randomized controlled multicenter trial, designed to investigate whether remote ischemic pre- and/or post-conditioning of the arm reduce the incidence of AF following CABG surgery.Trial registrationClinicalTrials.gov under NCT01107184.

Intraoperative real time three-dimensional transesophageal echocardiographic measurement of hemodynamic, anatomic and functional changes after aortic valve replacement.

The traditional intraoperative two‐dimensional transesophageal echocardiography (2DTEE) has limitations in measuring left ventricular ejection fraction (LVEF) because measurements rely on geometric assumptions. The availability of online software and real time three‐dimensional transesophageal echocardiography (RT3D‐TEE) makes intraoperative LVEF measurements fast and easy. This is the first report of intraoperative measurement of LVEF and aortic valve area (AVA) by RT3‐DTEE in a patient who received transcatheter‐based transapical aortic valve implantation.