Jari Halonen

Intravenous Administration of Metoprolol Is More Effective Than Oral Administration in the Prevention of Atrial Fibrillation After Cardiac Surgery

Background— Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery, with an incidence of 20% to 40%. AF is associated with postoperative complications, including increased risk of stroke and need of additional treatment, as well as prolonged hospital stay and increased costs. It has been shown that prophylactic oral administration of β-blocker therapy reduces the incidence of postoperative AF after cardiac surgery. However, it is possible that absorption of drugs is impaired after cardiopulmonary perfusion associated with cardiac surgery. The purpose of this prospective, controlled, randomized trial was to study compare intravenous and per oral metoprolol administration in the prevention of AF after cardiac surgery. Methods and Results— 240 consecutive patients who were scheduled to undergo their first on-pump coronary artery bypass graft (CABG), aortic valve replacement, or combined aortic valve replacement and CABG were randomized to receive 48-hour infusion of metoprolol or oral metoprolol starting on the first postoperative morning. Patients were excluded if they had contraindications for β-blocker or had to stay >1 day in the intensive care unit. Dosage of metoprolol was adjusted according to heart rate. The dosage was 1 to 3 mg/h in the intravenous group and from 25 mg twice per day to 50 mg 3 times per day in the oral group. The incidence of postoperative AF was significantly lower in the intravenous group than in the oral group (16.8% versus 28.1%, P=0.036). No serious adverse effects were associated with intravenous metoprolol therapy. Conclusions— Our study suggests that intravenous metoprolol is well-tolerated and more effective than oral metoprolol in the prevention of AF after cardiac surgery.

Metoprolol Versus Amiodarone in the Prevention of Atrial Fibrillation After Cardiac Surgery: A Randomized Trial

BACKGROUND Current guidelines recommend β-blockers as the first-line preventive treatment of atrial fibrillation (AF) after cardiac surgery. Despite this, 19% of physicians report using amiodarone as first-line prophylaxis of postoperative AF. Data directly comparing the efficacy of these agents in preventing postoperative AF are lacking. OBJECTIVE To determine whether intravenous metoprolol and amiodarone are equally effective in preventing postoperative AF after cardiac surgery. DESIGN Randomized, prospective, equivalence, open-label, multicenter study. (ClinicalTrials.gov registration number: NCT00784316) SETTING 3 cardiac care referral centers in Finland. PATIENTS 316 consecutive patients who were hemodynamically stable and free of mechanical ventilation and AF within 24 hours after cardiac surgery. INTERVENTION Patients were randomly assigned to receive 48-hour infusion of metoprolol, 1 to 3 mg/h, according to heart rate, or amiodarone, 15 mg/kg of body weight daily, with a maximum daily dose of 1000 mg, starting 15 to 21 hours after cardiac surgery. MEASUREMENTS The primary end point was the occurrence of the first AF episode or completion of the 48-hour infusion. RESULTS Atrial fibrillation occurred in 38 of 159 (23.9%) patients in the metoprolol group and 39 of 157 (24.8%) patients in the amiodarone group (P = 0.85). However, the difference (-0.9 percentage point [90% CI, -8.9 to 7.0 percentage points]) does not meet the prespecified equivalence margin of 5 percentage points. The adjusted hazard ratio of the metoprolol group compared with the amiodarone group was 1.09 (95% CI, 0.67 to 1.76). LIMITATIONS Caregivers were not blinded to treatment allocation, and the trial evaluated only stable patients who were not at particularly elevated risk for AF. The withdrawal of preoperative β-blocker therapy may have increased the risk for AF in the amiodarone group. CONCLUSION The occurrence of AF was similar in the metoprolol and amiodarone groups. However, because of the wide range of the CIs, the authors cannot conclude that the 2 treatments were equally effective. PRIMARY FUNDING SOURCE The Finnish Foundation for Cardiovascular Research and the Kuopio University EVO Foundation.

Association of objectively measured sedentary behaviour and physical activity with cardiovascular disease risk

Background We evaluated the association of accelerometer-based sedentary behaviour and physical activity with the risk of cardiovascular disease. Design The design of this study used a population-based, cross-sectional sample. Methods A subsample of participants in the Health 2011 Study in Finland used the tri-axial accelerometer (≥4 days, >10 h/day, n = 1398). Sedentary behaviour (sitting, lying) and standing still in six-second epochs were recognised from raw acceleration data based on intensity and device orientation. The intensity of physical activity was calculated as one-minute moving averages of mean amplitude deviation of resultant acceleration and converted to metabolic equivalents. Metabolic equivalents were categorised to light physical activity (1.5–2.9 metabolic equivalents) and moderate-to-vigorous physical activity (moderate-to-vigorous physical activity≥3.0 metabolic equivalents). Daily sedentary behaviour, standing still, light physical activity and moderate-to-vigorous physical activity were expressed as mean daily total time, accumulated time and number of different bouts (from 30 s to >30 min), mean daily metabolic equivalent and weekly peak metabolic equivalent levels of different bout lengths and number of breaks in sedentary behaviour. The ten-year cardiovascular disease risk was based on the Framingham risk model. Results The mean number of daily sedentary behaviour bouts was more strongly associated with cardiovascular disease risk than mean daily total time. In the best model, smaller waist circumference, greater value of mean daily metabolic equivalent levels of one-minute bouts, higher accumulated time of moderate-to-vigorous physical activity lasting ≤30 min, higher number of >5 min standing bouts and a higher number of long (>30 min) bouts of light physical activity were significantly associated with lower cardiovascular disease risk (R2 = 0.836). Conclusions The objectively measured number and accumulated time from different bout lengths of physical activity and sedentary behaviour were associated with cardiovascular disease risk, which is considered relevant for estimating cardiovascular diseases and for devising preventive actions.

Rewarming a Patient With Accidental Hypothermia and Cardiac Arrest Using Thoracic Lavage

The optimal treatment for severe accidental hypothermia is cardiopulmonary bypass because this offers the most rapid rate of rewarming. However, cardiopulmonary bypass therapy is not available in every hospital. In these circumstances, rewarming has to be achieved with other methods. We present a patient who was successfully rewarmed with thoracic lavage after he had been found with a core temperature of 21°C and asystole.

New onset postoperative atrial fibrillation and early anticoagulation after cardiac surgery

Abstract Objectives. New onset postoperative atrial fibrillation (POAF) after cardiac surgery is associated with increased risk for thromboembolic complications. Compliance with anticoagulation treatment is prerequisite for successful outcome after POAF. We hypothesized that a disciplined anticoagulation protocol initiated instantly after POAF secures a long-term outcome. Design. A total of 519 consecutive patients undergoing cardiac surgery were retrospectively analyzed. Patients received anticoagulation using warfarin whenever POAF lasted longer than five min. Postoperative outcome including mortality, myocardial infarction and stroke were compared with patients on sinus rhythm (non-POAF). Results. Mean age of the study cohort was 64.3 ± 9.0 years and median follow-up time was 76 months. There were 177 (34%) POAF and 342 (66%) non-POAF patients. At discharge, 144 (81%) POAF patients complied with warfarin, while 82 (24%) non-POAF patients received warfarin for non-rhythm causes (p < .001). Mortality was higher in POAF as compared with non-POAF patients (p = .03). After adjustment for comorbidities, major adverse clinical events (MACE)- including a combination of late cardiovascular mortality, myocardial infarction, stroke and late atrial fibrillation- was independently associated with POAF (OR 2.73, 95%CI 1.69-4.45, p < .0001). Conclusions. POAF after cardiac surgery was associated with high risk of MACE. Early anticoagulation may be justified in POAF patients to secure a long-term outcome after cardiac surgery.

Response to the letter to the editor by Dr. Yasar and Babaoglu on the recent publication of Kokki et al. on the pharmacokinetics of metoprolol bioavailability in coronary artery bypass surgery patients

Dear Editor, professor Rune Dahlqvist We are writing in response to the letter from Dr. Yasar and Babaoglu commenting on the recent publication by Kokki et al. [1] on the pharmacokinetics of metoprolol bioavailability in coronary artery bypass surgery patients. Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery. The reported incidence varies between 5.5 and 57% and is even higher after combined coronary artery bypass grafting (CABG) and valve surgery than after CABG alone. Postoperative AF is associated with serious complications, including increased risk of stroke and need of additional treatment, as well as prolonged hospital stay and increased costs. Beta blockers are commonly used in patients with cardiac surgery procedures. Despite this widely used therapy administrated bymouth, the incidence of postoperative AF is high. It is unknown why the beta blockers do not reduce the incidence of postoperative AF more efficiently. Valtola and colleagues [2] have evaluated in their study the bioavailability of perioperative metoprolol tablets in CABG patients. In that study, the bioavailability of beta blockers by mouth was significantly less postoperatively than on the preoperative day. They concluded that there may be several reasons for this poor absorption and low bioavailability. First, several patients should have had bowel dysfunction and delayed gastric emptying immediately following cardiac surgery, second, during and after major cardiovascular surgery using cardiopulmonary bypass, structural changes to the intestine may occur and result on villous atrophy and third, changes in splanchnic blood flow, oedema and mucosal ischemia, all commonly associated with cardiac surgery procedures, impair absorption by decreasing the effective absorptive area of the gut and reducing mucosal transport. Supporting these assumptions, Halonen and colleagues [3] showed in their prospective, randomized study, that intravenous metoprolol was more effective than tablets by mouth in the prevention of AF after cardiac surgery. The incidence of postoperative AF was significantly lower (16.8%) in the intravenous group than in the group where metoprolol was administered by mouth group (28.1%). In conclusion, the reduced bioavailability and poor effect of metoprolol administered by mouth is not associated with decreased metabolism the parent drug in liver. Theoretically, the reduced peak concentration and exposure to metoprolol on the first postoperative day can be explained by an increase in hepatic clearance and first-pass metabolism. However, we believe that this in unlikely because the splanchnic perfusion is decreased immediately after major surgery.

Subjects with cardiovascular disease or high disease risk are more sedentary and less active than their healthy peers

Objectives We investigated differences in objectively measured sedentary behaviour (SB) and physical activity (PA) levels in subjects with cardiovascular disease (CVD) diagnosis or high CVD risk compared with healthy controls. Methods The present study includes a subsample (n=1398, Health 2011 Study) of participants, who attended health examinations and wore a triaxial accelerometer (≥4 days). Patients with CVD were identified and CVD risk was calculated for others using Framingham Risk Score (FRS). Participants were categorised into groups: FRS<10%; FRS=10%–30%; FRS>30%/CVD. Raw acceleration data were analysed with mean amplitude deviation (MAD) and angle for posture estimation (APE). MAD corresponding to intensity of PA was converted to metabolic equivalents (MET) and categorised to light (1.5–2.9 METs) and moderate to vigorous PA (MVPA≥3.0 METs). APE recognises SB and standing. Results Daily accumulated time of >30 s MVPA bouts was higher in FRS<10% group (46 min) than in FRS>30%/CVD group (29 min) (p<0.001). FRS>30%/CVD group were more sedentary, their mean daily number of >10 min SB bouts (13.2) was higher than in FRS <10% group (11.5) (p=0.002). Conclusion Number and accumulated times of SB and PA bouts differed between the CVD risk groups. Causative research is required to assess the importance of SB and PA in prevention and rehabilitation of CVDs.

Spectral Entropy Parameters during Rapid Ventricular Pacing for Transcatheter Aortic Valve Implantation

The time-frequency balanced spectral entropy of the EEG is a monitoring technique measuring the level of hypnosis during general anesthesia. Two components of spectral entropy are calculated: state entropy (SE) and response entropy (RE). Transcatheter aortic valve implantation (TAVI) is a less invasive treatment for patients suffering from symptomatic aortic stenosis with contraindications for open heart surgery. The goal of hemodynamic management during the procedure is to achieve hemodynamic stability with exact blood pressure control and use of rapid ventricular pacing (RVP) that result in severe hypotension. The objective of this study was to examine how the spectral entropy values respond to RVP and other critical events during the TAVI procedure. Twenty one patients undergoing general anesthesia for TAVI were evaluated. The RVP was used twice during the procedure at a rate of 185 ± 9/min with durations of 16 ± 4 s (range 8–22 s) and 24 ± 6 s (range 18–39 s). The systolic blood pressure during RVP was under 50 ± 5 mmHg. Spectral entropy values SE were significantly declined during the RVP procedure, from 28 ± 13 to 23 ± 13 (p < 0.003) and from 29 ± 12 to 24 ± 10 (p < 0.001). The corresponding values for RE were 29 ± 13 vs. 24 ± 13 (p < 0.006) and 30 ± 12 vs. 25 ± 10 (p < 0.001). Both SE and RE values returned to the pre-RVP values after 1 min. Ultra-short hypotension during RVP changed the spectral entropy parameters, however these indices reverted rapidly to the same value before application of RVP.