Associations between mean arterial pressure during cardiopulmonary bypass and biomarkers of cerebral injury in patients undergoing cardiac surgery: secondary results from a randomized controlled trial.

OBJECTIVES: Cardiac surgery is associated with risk of cerebral injury and mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) is suggested to be associated with cerebral injury. The 'Perfusion Pressure Cerebral Infarcts' (PPCI) trial randomized patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement to a MAP of 40-50 or 70-80 mmHg during CPB and found no difference in clinical or imaging outcomes between the groups. We here present PPCI trial predefined secondary end points, consisting of biomarkers of brain injury. METHODS: Blood was collected from PPCI trial patients at baseline, 24 and 48 h after induction of anaesthesia and at discharge from the surgical ward. Blood was analysed for neuron-specific enolase, tau, neurofilament light and the glial marker glial fibrillary acidic protein. Linear mixed models were used to analyse differences in biomarker value changes from baseline between the 2 MAP allocation groups. RESULTS: A total of 193 (98%) patients were included. We found no differences in biomarker levels over time from baseline to discharge between the 2 MAP allocation groups (PNSE = 0.14, PTau = 0.46, PNFL = 0.21, PGFAP = 0.13) and the result did not change after adjustment for age, sex and type of surgery. CONCLUSIONS: We found no significant differences in levels of biomarkers of neurological injury in patients undergoing elective or subacute CABG and/or aortic valve replacement randomized to either a target MAP of 40-50 mmHg or a target MAP of 70-80 mmHg during CBP.

Blood pressure and brain injury in cardiac surgery: a secondary analysis of a randomized trial.

OBJECTIVES: Brain dysfunction is a serious complication after cardiac surgery. In the Perfusion Pressure Cerebral Infarcts trial, we allocated cardiac surgery patients to a mean arterial pressure of either 70-80 or 40-50 mmHg during cardiopulmonary bypass (CPB). In this secondary analysis, we compared selected cerebral metabolites using magnetic resonance spectroscopy hypothesizing that a postoperative decrease in occipital grey matter (GM) N-acetylaspartate-to-total-creatine ratio, indicative of ischaemic injury, would be found in the high-target group. METHODS: Of the 197 patients randomized in the Perfusion Pressure Cerebral Infarcts trial, 55 and 42 patients had complete and useful data from GM and white matter (WM), respectively. Spectroscopies were done preoperatively and on postoperative days 3-6. Cognitive function was assessed prior to surgery, at discharge and at 3 months. We predefined the statistical significance level to be 0.01. RESULTS: A postoperative decrease was found in GM N-acetylaspartate-to-total-creatine ratio in the high-target group [mean difference -0.09 (95% confidence interval -0.14 to -0.04), P = 0.014]. No significant differences were found in other metabolite ratios investigated in GM or WM. No significant association was found between changes in metabolite ratios and new cerebral infarcts, WM lesion score or cognitive dysfunction. CONCLUSIONS: A higher mean arterial pressure during CPB was associated with signs of impaired cerebral metabolism, though not at the predefined significance level of 0.01. No significant association was found between metabolite ratio changes and neuroradiological pathology or change in cognitive function. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT02185885.

Long-term survival and cognitive function according to blood pressure management during cardiac surgery. A follow-up.

BACKGROUND: Cardiac surgery is associated with a risk of complications, including post-operative cognitive dysfunction (POCD). In the randomized Perfusion Pressure Cerebral Infarcts (PPCI) trial, we allocated cardiac surgery patients to either a low-target mean arterial pressure (40-50 mm Hg) or a high-target pressure (70-80 mm Hg). The study found no difference in the volume of new ischemic cerebral lesions nor POCD, but 30-day mortality tended to be higher in the high-target group. In the present study we did a long-term 3-year follow-up to assess survival and level of cognitive functioning. The primary hypothesis was that patients allocated to a high-target blood pressure had a higher long-term mortality at 3-year follow-up. METHODS: We determined long-term mortality of patients included in the PPCI trial at 3-year follow-up using national registries and we assessed POCD using a cognitive test battery. Subjective level of functioning was assessed with questionnaires. POCD and subjective functioning at follow-up were evaluated in logistic regression models. RESULTS: Among the 197 patients who participated in the original study, there was no significant difference in mortality over a median of 3.4 years according to blood pressure target during cardiopulmonary bypass (hazards ratio 1.23 [high vs low] 95% confidence interval: 0.50-3.02, P = .65). POCD was found in 18.9% and 14.0% in the high-target and low-target groups, respectively adjusted odds ratio 1.01 (CI 95% 0.33-3.12). No differences were found for subjective functioning between groups. CONCLUSIONS: No difference in mortality nor in the level of cognitive functioning was found according to blood pressure target during cardiac surgery long-term at 3-year follow-up.

Higher arterial pressure during cardiopulmonary bypass may not reduce the risk of acute kidney injury.

BACKGROUND: Acute kidney injury after cardiac surgery is common and associated with increased mortality. It is unknown whether an intended higher arterial pressure during cardiopulmonary bypass reduces the incidence of acute and chronic kidney injury. METHODS: Patients were randomised either to a control group or a high pressure group (arterial pressure > 60 mmHg). The inclusion criteria were age > 70 years, combined cardiac surgery and serum creatinine < 200 µmol/L. Glomerular filtration rate using the Cr-EDTA clearance method was measured the day before surgery and 4 months postoperatively. The RIFLE criteria were used to define the presence of acute kidney injury. In addition, the ratio between urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) and creatinine was measured. RESULTS: Ninety patients were included. Mean age was 76 ± 4 years and 76% were male. Mean arterial pressure was 47 ± 5 mmHg in the control group and 61 ± 4 mmHg in the high pressure group (p < 0.0001). The change in glomerular filtration rate at follow-up was - 9 ± 12 ml/min in the control group and - 5 ± 16 ml/min in the high pressure group (p = 0.288, 95% CI - 13 to 4). According to the RIFLE criteria 38% in the control group and 46% in the high pressure group developed acute kidney injury (p = 0.447). The postoperative urinary NGAL/creatinine ratio was comparable between the groups. CONCLUSIONS: An intended increase in arterial pressure during cardiopulmonary bypass to > 60 mmHg did not decrease the incidence of acute or chronic kidney injury after cardiac surgery. TRIAL REGISTRATION: Clinicaltrials.gov, identifier: NCT01408420 . Registered 3rd of August 2011.

The association between postoperative cognitive dysfunction and cerebral oximetry during cardiac surgery: a secondary analysis of a randomised trial.

BACKGROUND: Postoperative cognitive dysfunction (POCD) occurs commonly after cardiac surgery. Near-infrared spectroscopy (NIRS) has been used to monitor regional cerebral oxygen saturation (rScO2) in order to minimise the occurrence of POCD by applying dedicated interventions when rScO2 decreases. However, the association between rScO2 intraoperatively and POCD has not been clarified. METHODS: This is a secondary analysis of a randomised trial with physician-blinded NIRS monitoring and cognitive testing at discharge from hospital and at 3 months after surgery. The association between intraoperative rScO2 values and POCD at discharge from hospital and at 3 months after surgery was investigated. The prespecified candidate predictive variable of interest was cumulative time during surgery with rScO2 ≥10% below its preoperative value. RESULTS: One hundred and fifty-three patients had complete NIRS data and neurocognitive assessments at discharge, and 44 of these patients (29%) had POCD. At 3 months, 148 patients had complete data, and 12 (8%) of these patients had POCD. The median time with rScO2 >10% below preoperative values did not differ for patients with and without POCD at discharge (difference=0.0 min; Hodges-Lehmann 95% confidence interval, -3.11-1.47, P=0.88). Other rScO2 time thresholds that were assessed were also not significantly different between those with and without POCD at discharge. This applied both to absolute rScO2 values and relative changes from preoperative values. Similar results were found in relation to POCD at 3 months. CONCLUSIONS: No significant association was found between intraoperative rScO2 values and POCD. These findings bring into question the rationale for attempting to avoid decreases in rScO2 if the goal is to prevent POCD. CLINICAL TRIAL REGISTRATION: NCT02185885.

Impact of 2 Distinct Levels of Mean Arterial Pressure on Near-Infrared Spectroscopy During Cardiac Surgery: Secondary Outcome From a Randomized Clinical Trial.

BACKGROUND: Near-infrared spectroscopy (NIRS) is used worldwide to monitor regional cerebral oxygenation (rScO2) during cardiopulmonary bypass (CPB). Intervention protocols meant to mitigate cerebral desaturation advocate to increase mean arterial pressure (MAP) when cerebral desaturation occurs. However, the isolated effect of MAP on rScO2 is uncertain. The aim of the present study was in a randomized, blinded design to elucidate the effect of 2 distinct levels of MAP on rScO2 values during CPB.We hypothesized that a higher MAP would be reflected in higher rScO2 values, lower frequency of patients with desaturation, and a less pronounced cerebral desaturation load. METHODS: This is a substudy of the Perfusion Pressure Cerebral Infarct trial, in which we investigated the impact of MAP levels during CPB on ischemic brain injury after cardiac surgery. Deviation in rScO2 was a predefined outcome in the Perfusion Pressure Cerebral Infarct trial. Patients were randomized to low MAP (LMAP; 40-50 mm Hg) or high MAP (HMAP; 70-80 mm Hg) during CPB. CPB pump flow was fixed at 2.4 L/min/m, and MAP levels were targeted using norepinephrine. Intraoperatively, NIRS monitoring was performed in a blinded fashion, with sensors placed on the left and right side of the patient's forehead. NIRS recordings were extracted for offline analysis as the mean value of left and right signal during prespecified periods. Mean rScO2 during CPB was defined as the primary outcome in the present study. RESULTS: The average MAP level during CPB was 67 mm Hg ± SD 5.0 in the HMAP group (n = 88) and 45 mm Hg ± SD 4.4 in the LMAP group (n = 88). Mean rScO2 was significantly lower in the HMAP group during CPB (mean difference, 3.5; 95% confidence interval, 0.9-6.1; P = .010). There was no difference in rScO2 values at specified time points during the intraoperative period between the 2 groups. Significantly more patients experienced desaturation below 10% and 20% relative to rScO2 baseline in the HMAP group (P = .013 and P = .009, respectively), and the cerebral desaturation load below 10% relative to rScO2 baseline was more pronounced in the HMAP group (P = .042). CONCLUSIONS: In a randomized blinded study, we observed that a higher MAP induced by vasopressors, with a fixed CPB pump flow, leads to lower mean rScO2 and more frequent and pronounced cerebral desaturation during CPB. The mechanism behind these observations is not clear. We cannot exclude extracranial contamination of the NIRS signal as a possible explanation. However, we cannot recommend increasing MAP by vasoconstrictors during cerebral desaturation because this is not supported by the findings of the present study.

Pediatric Transthoracic Cardiac Vector Flow Imaging - A Preliminary Pictorial Study.

Purpose Conventional pediatric echocardiography is crucial for diagnosing congenital heart disease (CHD), but the technique is impaired by angle dependency. Vector flow imaging (VFI) is an angle-independent noninvasive ultrasound alternative for blood flow assessment and can assess complex flow patterns not visible on conventional Doppler ultrasound. Materials and Methods 12 healthy newborns and 3 infants with CHD were examined with transthoracic cardiac VFI using a conventional ultrasound scanner and a linear array. Results VFI examinations revealed common cardiac flow patterns among the healthy newborns, and flow changes among the infants with CHD not previously reported with conventional echocardiography. Conclusion For assessment of cardiac flow in the normal and diseased pediatric heart, VFI may provide additional information compared to conventional echocardiography and become a useful diagnostic tool.

Resuscitation of Endotheliopathy and Bleeding in Thoracic Aortic Dissections: The VIPER-OCTA Randomized Clinical Pilot Trial.

BACKGROUND: Thoracic aorta dissection is an acute critical condition associated with shock-induced endotheliopathy, coagulopathy, massive bleeding, and significant morbidity and mortality. Our aim was to compare the effect of coagulation support with solvent/detergent-treated pooled plasma (OctaplasLG) versus standard fresh frozen plasma (FFP) on glycocalyx and endothelial injury, bleeding, and transfusion requirements. METHODS: Investigator-initiated, single-center, blinded, randomized clinical pilot trial of adult patients undergoing emergency surgery for thoracic aorta dissection. Patients were randomized to receive OctaplasLG or standard FFP as coagulation factor replacement related to bleeding. The primary outcome was glycocalyx and endothelial injury. Other outcomes included bleeding, transfusions and prohemostatics at 24 hours, organ failure, length of stay in the intensive care unit and in the hospital, safety, and mortality at 30 and 90 days. RESULTS: Fifty-seven patients were included to obtain 44 evaluable on the primary outcome. The OctaplasLG group displayed significantly reduced damage to the endothelial glycocalyx (syndecan-1) and reduced endothelial tight junction injury (sVE-cadherin) compared to standard FFP. In the OctaplasLG group compared to the standard FFP, days on ventilator (1 day [interquartile range, 0-1] vs 2 days [1-3]; P = .013), bleeding during surgery (2150 [1600-3087] vs 2750 [2130-6875]; P = .046), 24-hour total transfusion and platelet transfusion volume (3975 mL [2640-6828 mL] vs 6220 mL [4210-10,245 mL]; P = .040, and 1400 mL [1050-2625 mL] vs 2450 mL [1400-3500 mL]; P = .027), and goal-directed use of prohemostatics (7/23 [30.4%] vs 13/21 [61.9%]; P = .036) were all significantly lower. Among the 57 patients randomized, 30-day mortality was 20.7% (6/29) in the OctaplasLG group and 25% (7/28) in the standard FFP group (P = .760). No safety concern was raised. CONCLUSIONS: In this randomized, clinical pilot trial of patients undergoing emergency surgery for thoracic aorta dissections, we found that OctaplasLG reduced glycocalyx and endothelial injury, reduced bleeding, transfusions, use of prohemostatics, and time on ventilator after surgery compared to standard FFP. An adequately powered multicenter trial is warranted to confirm the clinical importance of the findings.

Impact of mean arterial pressure on sublingual microcirculation during cardiopulmonary bypass-Secondary outcome from a randomized clinical trial.

OBJECTIVE: In this substudy of a randomized, clinical trial, we explored the sublingual microcirculation during cardiac surgery at 2 different levels of blood pressure. We hypothesized that a higher map during CPB would cause higher MFI. METHODS: Thirty-six cardiac surgery patients undergoing CABG were included and randomized to either low (40-50 mm Hg) or high (70-80 mm Hg) MAP during CPB. SDF video images were recorded from the sublingual mucosa. Recordings were analyzed in a blinded fashion to quantify microcirculatory variables. RESULTS: MAP during CPB in the low target group was 45.0 mm Hg (SD: 5.3) vs 67.2 mm Hg (SD: 8.9) in the high target group. We found no significant difference between the 2 groups in MFI during CPB evaluated for AV: 2.91 vs 2.90 (P = .82). For sm AV (<20 µm), the corresponding values were 2.87 and 2.85 in the low and high target groups, respectively (P = .82). CONCLUSIONS: We found no significant difference in sublingual microcirculatory flow expressed as MFI according to 2 different levels of MAP during CPB.

Comparing Methods for Cardiac Output: Intraoperatively Doppler-Derived Cardiac Output Measured With 3-Dimensional Echocardiography Is Not Interchangeable With Cardiac Output by Pulmonary Catheter Thermodilution.

BACKGROUND: Estimation of cardiac output (CO) is essential in the treatment of circulatory unstable patients. CO measured by pulmonary artery catheter thermodilution is considered the gold standard but carries a small risk of severe complications. Stroke volume and CO can be measured by transesophageal echocardiography (TEE), which is widely used during cardiac surgery. We hypothesized that Doppler-derived CO by 3-dimensional (3D) TEE would agree well with CO measured with pulmonary artery catheter thermodilution as a reference method based on accurate measurements of the cross-sectional area of the left ventricular outflow tract. METHODS: The primary aim was a systematic comparison of CO with Doppler-derived 3D TEE and CO by thermodilution in a broad population of patients undergoing cardiac surgery. A subanalysis was performed comparing cross-sectional area by TEE with cardiac computed tomography (CT) angiography. Sixty-two patients, scheduled for elective heart surgery, were included; 1 was subsequently excluded for logistic reasons. Inclusion criteria were coronary artery bypass surgery (N = 42) and aortic valve replacement (N = 19). Exclusion criteria were chronic atrial fibrillation, left ventricular ejection fraction below 0.40 and intracardiac shunts. Nineteen randomly selected patients had a cardiac CT the day before surgery. All images were stored for blinded post hoc analyses, and Bland-Altman plots were used to assess agreement between measurement methods, defined as the bias (mean difference between methods), limits of agreement (equal to bias ± 2 standard deviations of the bias), and percentage error (limits of agreement divided by the mean of the 2 methods). Precision was determined for the individual methods (equal to 2 standard deviations of the bias between replicate measurements) to determine the acceptable limits of agreement. RESULTS: We found a good precision for Doppler-derived CO measured by 3D TEE, but although the bias for Doppler-derived CO by 3D compared to thermodilution was only 0.3 L/min (confidence interval, 0.04-0.58), there were wide limits of agreement (-1.8 to 2.5 L/min) with a percentage error of 55%. Measurements of cross-sectional area by 3D TEE had low bias of -0.27 cm (confidence interval, -0.45 to -0.08) and a percentage error of 18% compared to cardiac CT angiography. CONCLUSIONS: Despite low bias, the wide limits of agreement of Doppler-derived CO by 3D TEE compared to CO by thermodilution will limit clinical application and can therefore not be considered interchangeable with CO obtained by thermodilution. The lack of agreement is not explained by lack of agreement of the 3D technique.

High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial.

BACKGROUND: Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent strokes, detected by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients. METHODS: In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min-1·m-2. The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total number of new ischemic lesions. RESULTS: Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group (P=0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm3 (interquartile range, 0-118 mm3; range, 0-25 261 mm3) in the low-target group versus 29 mm3 (interquartile range, 0-143 mm3; range, 0-22 116 mm3) in the high-target group (median difference estimate, 0; 95% confidence interval, -25 to 0.028; P=0.99), as was the secondary outcome of number of new lesions (1 [interquartile range, 0-2; range, 0-24] versus 1 [interquartile range, 0-2; range, 0-29] respectively; median difference estimate, 0; 95% confidence interval, 0-0; P=0.71). No significant difference was observed in frequency of severe adverse events. CONCLUSIONS: Among patients undergoing on-pump cardiac surgery, targeting a higher versus a lower mean arterial pressure during cardiopulmonary bypass did not seem to affect the volume or number of new cerebral infarcts. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02185885.

Transesophageal Doppler reliably tracks changes in cardiac output in comparison with intermittent pulmonary artery thermodilution in cardiac surgery patients.

In this study a comparison of cardiac output (CO) measurements obtained with CardioQ transesophageal Doppler (TED) and pulmonary artery catheter (PAC) thermodilution (TD) technique was done in a systematic set-up, with induced changes in preload, afterload and heart rate. Twenty-five patients completed the study. Each patient were placed in the following successive positions: (1) supine, (2) head-down tilt, (3) head-up tilt, (4) supine, (5) supine with phenylephrine administration, (6) pace heart rate 80 beats per minute (bpm), (7) pace heart rate 110 bpm. The agreement of compared data was investigated by Bland-Altman plots, and to assess trending ability a four quadrants plot and a polar plot were constructed. Both methods showed an acceptable precision 6.4 % (PAC TD) and 12.8 % (TED). In comparison with PAC TD, the TED was associated with a mean bias in supine position of -0.30 l min-1 (95 % CI -0.88; 0.27), wide limits of agreement, a percentage error of 69.5 %, and a trending ability with a concordance rate of 92 %, angular bias of 1.1° and a radial sector size of 40.0° corresponding to an acceptable trending ability. In comparison with PAC TD, the CardioQ TED showed a low mean bias, wide limits of agreement and a larger percentage error than should be expected from the precision of the two methods. However, an acceptable trending ability was found. Thus, the CardioQ TED should not replace CO measurements done by PAC TD, but could be a valuable tool in guiding therapy.

Right ventricular dysfunction after cardiac surgery - diagnostic options.

Right ventricular (RV) failure after cardiac surgery is associated with an ominous prognosis. The etiology of RV failure is multifaceted and the ability to recognize RV failure early is paramount in order to initiate timely treatment. The present review focuses on different diagnostic modalities for RV function and discusses the normal versus abnormal findings in RV monitoring after cardiac surgery and the limitations of the applicable diagnostic modalities. There are specific challenges in RV assessment after cardiac surgery due to a loss of longitudinal contraction and a concomitant gain of transverse contraction. Additionally, the image quality of transthoracic echocardiography (TTE) is often reduced after cardiac surgery. RV function can be assessed with 2D and 3D imaging techniques as well as invasive hemodynamic monitoring. Until proper validation studies have determined accuracy, reproducibility and comparability of the next generation of diagnostic modalities we propose to use simple, but obtainable echocardiographic measurements and ultimately the insertion of a pulmonary artery catheter (PAC) in order to diagnose RV failure after cardiac surgery.

Perfusion Pressure Cerebral Infarct (PPCI) trial - the importance of mean arterial pressure during cardiopulmonary bypass to prevent cerebral complications after cardiac surgery: study protocol for a randomised controlled trial.

BACKGROUND: Debilitating brain injury occurs in 1.6-5 % of patients undergoing cardiac surgery with cardiopulmonary bypass. Diffusion-weighted magnetic resonance imaging studies have reported stroke-like lesions in up to 51 % of patients after cardiac surgery. The majority of the lesions seem to be caused by emboli, but inadequate blood flow caused by other mechanisms may increase ischaemia in the penumbra or cause watershed infarcts. During cardiopulmonary bypass, blood pressure can be below the lower limit of cerebral autoregulation. Although much debated, the constant blood flow provided by the cardiopulmonary bypass system is still considered by many as appropriate to avoid cerebral ischaemia despite the low blood pressure. METHODS/DESIGN: The Perfusion Pressure Cerebral Infarct trial is a single-centre superiority trial with a blinded outcome assessment. The trial is randomising 210 patients with coronary vessel and/or valve disease and who are undergoing cardiac surgery with the use of cardiopulmonary bypass. Patients are stratified by age and surgical procedure and are randomised 1:1 to either an increased mean arterial pressure (70-80 mmHg) or 'usual practice' (40-50 mmHg) during cardiopulmonary bypass. The cardiopulmonary bypass pump flow is fixed and set at 2.4 L/minute/m(2) body surface area plus 10-20 % in both groups. The primary outcome measure is the volume of the new ischaemic cerebral lesions (in mL), expressed as the difference between a baseline, diffusion-weighted, magnetic resonance imaging scan and an equal scan conducted 3-6 days postoperatively. Secondary endpoints are the total number of new ischaemic cerebral lesions, postoperative cognitive dysfunction at discharge and 3 months postoperatively, diffuse cerebral injury evaluated by magnetic resonance spectroscopy and selected biochemical markers of cerebral injury. The sample size will enable us to detect a 50 % reduction in the primary outcome measure in the intervention compared to the control group at a significance level of 0.05 and with a power of 0.80. DISCUSSION: This is the first clinical randomised study to evaluate whether the mean arterial pressure level during cardiopulmonary bypass influences the development of brain injuries that are detected by diffusion-weighted magnetic resonance imaging. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02185885 . Registered on 7 July 2014.

Does depth of the frontal sinus affect near-infrared spectroscopy measurement?

Near-infrared spectroscopy (NIRS) is a non-invasive method that reflects real-time cerebral oxygenation (rSO2) by the use of two adhesive optodes placed on the forehead of the patient. Frontal sinuses vary anatomically and a large frontal sinus might compromise the NIRS signal since the NIRS optodes are placed at the skin surface superficial to the underlying frontal sinus. The aim of this case-series was to elucidate whether there is a difference in the obligate changes in rSO2 during cardiac surgery between patients with a small as opposed to a large anterior-posterior distance of the frontal sinus based on magnetic resonance imaging. Two matched groups with small (n = 5) vs. large (n = 5) frontal sinus (3.2 vs. 18.1 millimeters) in this case-series showed no difference in obligate changes of rSO2 (p = 0.54).

Acute kidney injury is independently associated with higher mortality after cardiac surgery.

OBJECTIVES: To investigate the incidence of acute kidney injury after cardiac surgery and its association with mortality in a patient population receiving ibuprofen and gentamicin perioperatively. DESIGN: Retrospective study with Cox regression analysis to control for possible preoperative, intraoperative and postoperative confounders. SETTING: University hospital-based single-center study. PARTICIPANTS: All patients who underwent coronary artery bypass grafting ± valve surgery during 2012. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Acute surgery within 24 hours of coronary angiography, previous nephrectomy, preoperative sCr >2.26 mg/dL and selective cerebral perfusion during cardiopulmonary bypass were used as exclusion criteria. Acute kidney injury was defined, using the Acute Kidney Injury Network (AKIN) criteria. Six hundred eight patients were included in the study. Mean age was 68.2 ± 9.7 years, and 81% were males. Acute kidney injury was seen in 28.1% of the patients. Overall mortality at one year was 7% and 3% in the no-AKI group. At one year, mortality was 15% in patients with AKIN stage 1 and AKIN stage 2 compared to 70% in AKIN stage 3. A hazard ratio of 2.34 (95% CI: 1.21-4.51, p = 0.011) and 5.62 (95% CI: 2.42-13.06), p<0.0001) were found for AKIN stage 1 and 2/3 combined, respectively. CONCLUSIONS: More than 28% of the patients undergoing elective or subacute cardiac surgery developed AKI in this contemporary cohort. Furthermore, acute kidney injury was an independent predictor of increased mortality irrespective of the perioperative risk factors.

Right ventricular failure after implantation of a continuous-flow left ventricular assist device: early haemodynamic predictors.

OBJECTIVES: Right ventricular failure (RVF) is a significant complication after implantation of a left ventricular assist device. We aimed to identify haemodynamic changes in the early postoperative phase that predicted subsequent development of RVF in a cohort of HeartMate II (HMII) implanted patients. METHODS: This was a single-centre observational study of consecutive placement of HMII devices at Rigshospitalet, Copenhagen. Preoperative data (right heart catheterization, biochemistry and clinical status) and postoperative readings from the first 72 h after implantation (haemodynamics, inotropic and vasoactive therapy) were included in the analysis. The data set was examined for significant differences between patients who developed RVF (RVF group, n = 11)-defined as need for inotropic or vasodilator therapy >14 days, nitric oxide therapy ≥ 48 h or right ventricular assist device therapy-and those who did not (non-RVF group, n = 22). RESULTS: Preoperative right heart catheterization data were similar in the two groups. Immediately after HMII implantation, the increase in cardiac index (CI) was significantly larger in the non-RVF than in the RVF group (0.96 ± 0.8 vs 0.2 ± 0.5 L/min, respectively; P = 0.018), whereas right ventricular stroke work index (RVSWI) decreased significantly more in the RVF group (-4.3 ± 2.0 vs -0.9 ± 2.0 g m/m(2); P < 0.001). These differences were present in spite of the RVF group receiving larger doses of catecholaminergic agents (P = 0.034). Over the ensuing 72 h, the CI of the RVF group gradually approached that of the non-RVF group; concurrently, however, the differences in inotropic therapy were further enhanced. Pump settings were similar in the two groups. CONCLUSIONS: The haemodynamic alterations characterizing RVF were present already immediately after HMII implantation. RVF development was not related to pump flow and settings.

Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms, left ventricular perfusion and function in patients with severe chronic ischemic heart disease.

OBJECTIVES: A phase I safety and efficacy study with granulocyte colony stimulating factor (G-CSF) mobilization of bone marrow stem cells to induce vasculogenesis in patients with severe ischemic heart disease (IHD) was conducted. DESIGN, PATIENTS AND RESULTS: 29 patients with IHD participated in the study. Thirteen patients were treated with G-CSF for 6 days and 16 patients served as controls. G-CSF treatment was without any serious adverse events. Four patients were "poor mobilizers" with a maximal increase in CD34+ cells to 5,000+/-700/mL blood (mean+/-S.D.) compared to 28,900+/-5,100/mL blood in "mobilizers". At the follow-up, G-CSF treated had improved in CCS classification, NTG consumption and angina attacks, but the controls only in CCS classification. No difference was seen between the two groups. The decline in NTG consumption tended to be significant in "mobilizers" compared to controls. Myocardial perfusion was unchanged at adenosine stress single photon emission computerized tomography (SPECT) or magnetic resonance images (MRI). Left ventricular ejection fraction decreased from 57% to 52% (p<0.01, MRI) and from 48% to 44% (p=0.07, SPECT) in G-CSF treated, but was unchanged measured with echocardiography. CONCLUSIONS: Treatment by G-CSF improved symptoms but not signs of myocardial ischemia in patients with severe IHD. The effects seemed related to mobilization of stem cells. An adverse effect on ejection fraction could not be excluded.

Neurohumoral prediction of left-ventricular morphologic response to beta-blockade with metoprolol in chronic left-ventricular systolic heart failure.

BACKGROUND: In order to tailor therapy in heart failure, a solution might be to develop sensitive and reliable markers that can predict response in individual patients or monitor effectiveness of therapy. AIMS: To evaluate neurohumoral factors as markers for left-ventricular (LV) antiremodelling from metoprolol treatment in patients with chronic LV systolic heart failure. METHODS: Forty-one subjects randomised to placebo or metoprolol were studied with magnetic resonance imaging and blood samples to measure LV dimensions and ejection fraction, epinephrine, norepinephrine, plasma renin activity, aldosterone, atrial (ANP) and brain natriuretic peptides, arginine-vasopressin and endothelin-1 at baseline, 5 weeks and 6 months after randomisation. RESULTS: Baseline ANP was identified as sole independent marker for changes in LV end-diastolic (deltaLVEDVI: r=-0.70, P=0.002), and end-systolic (deltaLVESVI: r=-0.53, P=0.03) volumes during metoprolol treatment. Change in ANP during the study was an independent marker for deltaLVEDVI: r=0.66, P=0.004, and deltaLVESVI: r=0.69, P=0.002 in the entire metoprolol group, but at the individual patient level, results were less clear. CONCLUSION: The pre-treatment plasma level of ANP may be a predictor of LV antiremodelling from treatment with metoprolol in patients with chronic heart failure. However, the potential for individual neurohumoral monitoring of the effects on LV dimensions during beta-blockade appears limited.