Morbidity and mortality in patients managed with high compared with low blood pressure targets during on-pump cardiac surgery: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Many believe that blood pressure management during cardiac surgery is associated with postoperative outcomes. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to determine the impact of high compared with low intraoperative blood pressure targets on postoperative morbidity and mortality in adults undergoing cardiac surgery on cardiopulmonary bypass (CPB). Our primary objective was to inform the design of a future large RCT. SOURCE: We searched MEDLINE, EMBASE, Web of Science, CINAHL, and CENTRAL for RCTs comparing high with low intraoperative blood pressure targets in adult patients undergoing any cardiac surgical procedure on CPB. We screened reference lists, grey literature, and conference proceedings. PRINCIPAL FINDINGS: We included eight RCTs (N =1,116 participants); all examined the effect of blood pressure management only during the CPB. Trial definitions of high compared with low blood pressure varied and, in some, there was a discrepancy between the target and achieved mean arterial pressure. We observed no difference in delirium, cognitive decline, stroke, acute kidney injury, or mortality between high and low blood pressure targets (very-low to low quality evidence). Higher blood pressure targets may have increased the risk of requiring a blood transfusion (three trials; n = 456 participants; relative risk, 1.4; 95% confidence interval, 1.1 to 1.9; P = 0.01; moderate quality evidence) but this finding was based on a small number of trials. CONCLUSION: Individual trial definitions of high and low blood pressure targets varied, limiting inferences. The effect of high (compared with low) blood pressure targets on other morbidity and mortality after cardiac surgery remains unclear because of limitations with the body of existing evidence. Research to determine the optimal management of blood pressure during cardiac surgery is required. STUDY REGISTRATION: PROSPERO (CRD42020177376); registered: 5 July 2020.

RéSUMé: OBJECTIF: Pour beaucoup, la prise en charge de la pression artérielle pendant la chirurgie cardiaque serait associée aux issues postopératoires. Nous avons réalisé une revue systématique et une méta-analyse d'études randomisées contrôlées (ERC) afin de déterminer l'impact de cibles peropératoires de pression artérielle élevées par rapport à des cibles basses sur la morbidité et la mortalité postopératoires d'adultes bénéficiant d'une chirurgie cardiaque sous circulation extracorporelle (CEC). Notre objectif principal était d'orienter la conception d'une future ERC d'envergure. SOURCES: Nous avons analysé les bases de données MEDLINE, EMBASE, Web of Science, CINAHL et CENTRAL afin d'en tirer les ERC comparant des cibles de pression artérielle peropératoire élevées à des cibles basses chez des patients adultes bénéficiant d'une intervention chirurgicale cardiaque sous CEC. Nous avons passé au crible les listes de références, la littérature grise et les travaux de congrès. CONSTATATIONS PRINCIPALES: Nous avons inclus huit ERC (N = 1116 participants); toutes les études ont examiné l'effet de la prise en charge de la pression artérielle uniquement pendant la CEC. Les définitions d'une pression artérielle élevée ou basse variaient d'une étude à l'autre et, dans certains cas, un écart a été noté entre la pression artérielle cible et la pression artérielle moyenne atteinte. Nous n'avons observé aucune différence dans les taux de delirium, de déclin cognitif, d'accident vasculaire cérébral, d'insuffisance rénale aiguë ou de mortalité entre les cibles de pression artérielle élevée et basse (données probantes de qualité très faible à faible). Des cibles de pression artérielle plus élevées pourraient avoir augmenté le risque de transfusion sanguine (trois études; n = 456 participants; risque relatif, 1,4; intervalle de confiance à 95 %, 1,1 à 1,9; P = 0,01; données probantes de qualité modérée), mais ce résultat se fondait sur un petit nombre d'études. CONCLUSION: Les définitions individuelles des cibles d'hypertension et d'hypotension artérielle variaient, ce qui a limité les inférences. L'effet de cibles de pression artérielle élevée (par rapport à une pression artérielle basse) sur d'autres mesures de la morbidité et de la mortalité après une chirurgie cardiaque demeure incertain en raison des limites de l'ensemble des données probantes existantes. Des recherches visant à déterminer la prise en charge optimale de la pression artérielle pendant la chirurgie cardiaque sont nécessaires. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42020177376); enregistrée le 5 juillet 2020.

Biomarkers of Cerebral Injury for Prediction of Postoperative Cognitive Dysfunction in Patients Undergoing Cardiac Surgery.

OBJECTIVES: To assess the ability of the biomarkers neuron-specific enolase (NSE), tau, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP) to predict postoperative cognitive dysfunction (POCD) at discharge in patients who underwent cardiac surgery. DESIGN: Post hoc analyses (with tests being prespecified before data analyses) from a randomized clinical trial. SETTING: Single-center study from a primary heart center in Denmark. PARTICIPANTS: Adult patients undergoing elective or subacute on-pump coronary artery bypass grafting and/or aortic valve replacement. INTERVENTIONS: Blood was collected before induction of anesthesia, after 24 hours, after 48 hours, and at discharge from the surgical ward. The International Study of Postoperative Cognitive Dysfunction test battery was applied to diagnose POCD at discharge and after three months. Linear mixed models of covariance were used to assess whether repeated measurements of biomarker levels were associated with POCD. Receiver operating characteristic (ROC) curves were applied to assess the predictive value of each biomarker measurement for POCD. MEASUREMENTS AND MAIN RESULTS: A total of 168 patients had biomarkers measured at baseline, and 47 (28%) fulfilled the POCD criteria at discharge. Patients with POCD at discharge had significantly higher levels of tau (p = 0.02) and GFAP (p = 0.01) from baseline to discharge. The biomarker measurements achieving the highest area under the ROC curve for prediction of POCD at discharge were NFL measured at discharge (AUC, 0.64; 95% confidence interval [CI], 0.54-0.73), GFAP measured 48 hours after induction (AUC, 0.64; 95% CI, 0.55-0.73), and GFAP measured at discharge (AUC, 0.64; 95% CI, 0.54-0.74), corresponding to a moderate predictive ability. CONCLUSIONS: Postoperative serum levels of tau and GFAP were significantly elevated in cardiac surgery patients with POCD at discharge, however, the biomarkers achieved only modest predictive abilities for POCD at discharge. Postoperative levels of NSE were not associated with POCD at discharge.

Prognostic Value of Soluble Urokinase-Type Plasminogen Activator Receptor and High-Sensitivity C-Reactive Protein on Postoperative Mortality in Patients Undergoing Elective On-Pump Cardiac Surgery.

OBJECTIVES: Elevated soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP) have been associated with increased mortality in patients with cardiovascular disease. The aim of the present study was to explore the relationship between suPAR and hsCRP values and associated mortality after elective cardiac surgery. A secondary aim was to assess whether a combined risk model of European System for Cardiac Operative Risk Evaluation (EuroSCORE II), suPAR, and/or hsCRP would improve the prognostic accuracy compared with EuroSCORE II alone. DESIGN: Retrospective observational study. SETTING: Single-center, university hospital. PARTICIPANTS: Adult patients admitted for elective on-pump cardiac surgery were included. Biobank blood samples were obtained from previous research projects at a tertiary heart center from 2012 to 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 931 patients were included. Kaplan-Meier and Cox proportional hazard analyses were used to explore a potential association between preoperative suPAR and hsCRP values and all-cause mortality up to one year after surgery. Thirty-day mortality was predicted from suPAR, hsCRP, and EuroSCORE II by logistic regression and compared using area under the receiver operating characteristics curve and Brier scores. After adjustment for known confounders, a doubling of suPAR and hsCRP corresponded to a hazard ratio for all-cause mortality of 2.27 (95% confidence interval 1.65-3.11; p < 0.001) and 1.26 (95% confidence interval 1.07-1.49; p = 0.005), respectively. However, adding the biomarkers to EuroSCORE II did not improve prediction/discrimination with respect to 30-day mortality. CONCLUSIONS: Elevated preoperative levels of suPAR and hsCRP were associated with all-cause mortality in elective cardiac surgery patients. However, inclusion of biomarkers did not improve the prognostic accuracy of EuroSCORE II.

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.

Lack of Association Between Gaseous Microembolisms Assessed by a Single Detection Device and Cerebral Complications in Cardiac Surgery Patients.

OBJECTIVE: To assess the association between total volume and number of gaseous microemboli (GME) in the cardiopulmonary bypass (CPB) circuit and the occurrence of new postoperative cerebral infarctions and postoperative cognitive dysfunction (POCD) in patients undergoing cardiac surgery. DESIGN: Predefined subanalyses of the randomized controlled Perfusion Pressure Cerebral Infarcts (PPCI) trial. SETTING: Primary heart center in a university hospital. PARTICIPANTS: A total of 143 adult patients undergoing cardiac surgery with CPB. INTERVENTIONS: Patients were allocated 1:1 to a low-target mean arterial pressure (MAP) of 40 to 50 mmHg or a high-target MAP of 70 to 80 mmHg during CPB with a fixed pump flow of 2.4 liters per minute per square meter body surface area plus 10% to 20%. MEASUREMENTS AND MAIN RESULTS: The total volume and number of GME in the CPB circuit were assessed by the Bubble Counter Clinical 200® (GAMPT GmbH). New cerebral infarcts were identified by diffusion-weighted magnetic resonance imaging (DWI) 3 to 6 days after surgery. The median number of GME per patient was 8069 (range 1,523-204,095) with a median total volume of 1.2 µL (range 0.07-48 µL). A total of 66 (46%) patients had DWI detected cerebral infarcts postoperatively, and 36 (28%) patients had POCD after 7 days. The authors found no significant association between volume or number of GME with MAP target allocation, presence of cerebral infarction, or POCD. CONCLUSIONS: The authors found no significant associations between volume or number of GME with the occurrence of cerebral infarction or cognitive dysfunction in cardiac surgery patients.

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.

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.

Domain-specific cognitive dysfunction after cardiac surgery. A secondary analysis of a randomized trial.

BACKGROUND: Brain injury and cognitive dysfunction are serious complications after cardiac surgery. In the perfusion pressure cerebral infarcts (PPCI) trial, we allocated cardiac surgery patients to a mean arterial pressure of either 70-80 mm Hg (high-target) or 40-50 mm Hg (low-target) during cardiopulmonary bypass. In this secondary analysis, we aimed to assess potential differences in domain-specific patterns of cognitive deterioration between allocation groups and to investigate any associations of postoperative cognitive dysfunction (POCD) with diffusion-weighted magnetic resonance imaging (DWI)-detected brain lesions. METHODS: Of the 197 patients randomized in the PPCI trial, 89 in the low-target group and 80 in the high-target group had complete DWI datasets, and 92 and 80 patients had complete data for an evaluation of cognitive function at discharge respectively. Cognitive function was assessed prior to surgery, at discharge and at 3 months. DWI was obtained at baseline and on postoperative days 3 to 6. RESULTS: We found no statistically significant differences between the two groups when comparing the proportion of patients with a domain-specific deterioration over the pre-defined critical level in seven individual test variables at discharge. Significant deterioration was most common in tests thought to assess cognitive flexibility and interference susceptibility and least common in the memory test. POCD at discharge was more frequent in patients with DWI-positive brain lesions (OR adjusted for age and group allocation: 2.24 [95% CI 1.48-3.00], P = 0.036). CONCLUSIONS: Domain-specific patterns of POCD were comparable between groups. A significant association was seen between DWI-positive brain lesions and POCD.

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.

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).

A comparison of the AMBU ISCOPE and Macintosh laryngoscopes: first experience with a new device for tracheal intubation: a manikin study.

CONTEXT: Video laryngoscopes achieve laryngeal visualisation through indirect imaging using video cameras that look around the curve of the tongue. The new AMBU ISCOPE intubation device combines features from the laryngeal mask airway with video laryngoscopy enabling visual control of tracheal intubation without the use of a stylet. OBJECTIVE: We hypothesised that the AMBU ISCOPE would shorten the time taken to intubate a manikin compared to the Macintosh laryngoscope. DESIGN: Crossover study. SETTING: University hospital in Denmark. STUDY PERIOD: April 2011. PARTICIPANTS: We enrolled 36 trainees (19 nurse anaesthetists and 17 anaesthetists) with a median of 7 months of experience in anaesthesia (interquartile range 5 to 7.5 months). INTERVENTION: Tracheal intubation of a manikin, the Laerdal Airway Management Trainer, using either the AMBU ISCOPE, a new intubation conduit, or a conventional Macintosh laryngoscope. Every trainee performed three tracheal intubations with each device. MAIN OUTCOME MEASURES: The primary end-point was time to intubation. Secondary end-points were Cormack & Lehane grade and dental contact. RESULTS: Median time to tracheal intubation was 33.5 s using a Macintosh laryngoscope and 41.5 s using the AMBU ISCOPE device (P = 0.008). In both groups, 97% of intubations were successful. Ninety-seven percent of laryngeal visualisations achieved using the AMBU ISCOPE device were reported to be Cormack & Lehane grade 1 versus 57% for the Macintosh laryngoscope (P = 0.0001). CONCLUSION: Tracheal intubation time was significantly longer in trainees using the AMBU ISCOPE intubation device compared to a Macintosh laryngoscope, but with a difference of only 8 s. Laryngeal visualisation was significantly better using the AMBU ISCOPE device, but success rates for intubation were the same.

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.

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.