Non-invasive optical neuromonitoring of the temperature-dependence of cerebral oxygen metabolism during deep hypothermic cardiopulmonary bypass in neonatal swine.
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SUBMITTER: Ko TS
PROVIDER: S-EPMC6928559 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.
| S-EPMC5343476 | biostudies-literature
Project description:Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO2) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate-pyruvate ratio) and injury (glycerol). We applied a novel theoretical approach to correct for hematocrit variation during optical quantification of CBF in vivo. Without correction, a mean (95% CI) +53% (42, 63) increase in hematocrit resulted in a physiologically improbable +58% (27, 90) increase in CMRO2 relative to baseline at CPB initiation; following correction, CMRO2 did not differ from baseline at this timepoint. After CPB initiation, OEF increased but CBF and CMRO2 decreased with CPB time; these temporal trends persisted for 0-8 h following CPB and coincided with a 48% (7, 90) elevation of glycerol. The temporal trends and glycerol elevation resolved by 8-24 h. The hematocrit correction improved quantification of cerebral physiologic trends that precede and coincide with neurological injury following CPB.
| S-EPMC10672802 | biostudies-literature
Project description:BackgroundPatient rewarming after hypothermic cardiopulmonary bypass (CPB) has been linked to brain injury after cardiac surgery. In this study, we evaluated whether cooling and then rewarming of body temperature during CPB in adult patients is associated with alterations in cerebral blood flow (CBF)-blood pressure autoregulation.MethodsOne hundred twenty-seven adult patients undergoing CPB during cardiac surgery had transcranial Doppler monitoring of the right and left middle cerebral artery blood flow velocity. Eleven patients undergoing CPB who had arterial inflow maintained at >35 degrees C served as controls. The mean velocity index (Mx) was calculated as a moving, linear correlation coefficient between slow waves of middle cerebral artery blood flow velocity and mean arterial blood pressure. Intact CBF-blood pressure autoregulation is associated with an Mx that approaches 0. Impaired autoregulation results in an increasing Mx approaching 1.0. Comparisons of time-averaged Mx values were made between the following periods: before CPB (baseline), during the cooling and rewarming phases of CPB, and after CPB. The number of patients in each phase of CPB with an Mx >4.0, indicative of impaired CBF autoregulation, was determined.ResultsDuring cooling, Mx (left, 0.29 +/- 0.18; right, 0.28 +/- 0.18 [mean +/- SD]) was greater than that at baseline (left, 0.17 +/- 0.21; right, 0.17 +/- 0.20; P <or= 0.0001). Mx increased during the rewarming phase of CPB (left, 0.40 +/- 0.19; right, 0.39 +/- 0.19) compared with baseline (P <or= 0.001) and the cooling phase (P <or= 0.0001), indicating impaired CBF autoregulation. After CPB, Mx (left, 0.27 +/- 0.20; right, 0.28 +/- 0.21) was higher than at baseline (left, P = 0.0004; right, P = 0.0003), no different than during the cooling phase, but lower than during rewarming (left, P <or= 0.0001; right, P <or= 0.0005). Forty-three patients (34%) had an Mx >or=0.4 during the cooling phase of CPB and 68 (53%) had an average Mx >or=0.4 during rewarming. Nine of the 11 warm controls had an average Mx >or=0.4 during the entire CPB period. There were 7 strokes and 1 TIA after surgery. All strokes were in patients with Mx >or= 0.4 during rewarming (P = 0.015). The unadjusted odds ratio for any neurologic event (stroke or transient ischemic attack) for patients with Mx >or= 0.4 during rewarming was 6.57 (95% confidence interval, 0.79 to 55.0, P < 0.08).ConclusionsHypothermic CPB is associated with abnormal CBF-blood pressure autoregulation that is worsened with rewarming. We found a high rate of strokes in patients with evidence of impaired CBF autoregulation. Whether a pressure-passive CBF state during rewarming is associated with risk for ischemic brain injury requires further investigation.
| S-EPMC5516214 | biostudies-literature
Project description:Deep hypothermic circulatory arrest (DHCA) is a protective method against brain ischemia in aortic surgery. However, the possible effects of DHCA on the plasma proteins remain to be determined. In the present study, we used novel high‑throughput technology to compare the plasma proteomes during DHCA (22˚C) with selective cerebral perfusion (SCP, n=7) to those during normothermic cardiopulmonary bypass (CPB, n=7). Three plasma samples per patient were obtained during CPB: T1, prior to cooling; T2, during hypothermia; T3, after rewarming for the DHCA group and three corresponding points for the normothermic group. A proteomic analysis was performed using isobaric tag for relative and absolute quantification (iTRAQ) labeling tandem mass spectrometry to assess quantitative protein changes. In total, the analysis identified 262 proteins. The bioinformatics analysis revealed a significant upregulation of complement activation at T2 in normothermic CPB, which was suppressed in DHCA. These findings were confirmed by the changes of the terminal complement complex (SC5b‑9) levels. At T3, however, the level of SC5b‑9 showed a greater increase in DHCA compared to normothermic CPB, while 48 proteins were significantly downregulated in DHCA. The results demonstrated that DHCA and rewarming potentially exert a significant effect on the plasma proteome in patients undergoing aortic surgery.
| S-EPMC4152143 | biostudies-literature
Project description:Neurologic injury is a leading cause of morbidity and mortality following pediatric cardiac arrest. In this study, we assess the feasibility of quantitative, non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) neuromonitoring during cardiopulmonary resuscitation (CPR), and its predictive utility for return of spontaneous circulation (ROSC) in an established pediatric swine model of cardiac arrest. Cerebral tissue optical properties, oxy- and deoxy-hemoglobin concentration ([HbO2], [Hb]), oxygen saturation (StO2) and total hemoglobin concentration (THC) were measured by a FD-DOS probe placed on the forehead in 1-month-old swine (8-11 kg; n = 52) during seven minutes of asphyxiation followed by twenty minutes of CPR. ROSC prediction and time-dependent performance of prediction throughout early CPR (< 10 min), were assessed by the weighted Youden index (Jw, w = 0.1) with tenfold cross-validation. FD-DOS CPR data was successfully acquired in 48/52 animals; 37/48 achieved ROSC. Changes in scattering coefficient (785 nm), [HbO2], StO2 and THC from baseline were significantly different in ROSC versus No-ROSC subjects (p < 0.01) after 10 min of CPR. Change in [HbO2] of + 1.3 µmol/L from 1-min of CPR achieved the highest weighted Youden index (0.96) for ROSC prediction. We demonstrate feasibility of quantitative, non-invasive FD-DOS neuromonitoring, and stable, specific, early ROSC prediction from the third minute of CPR.
| S-EPMC7884428 | biostudies-literature
Project description:Essentials Heparin-protamine balance (HPB) modulates bleeding after neonatal cardiopulmonary bypass (CPB). HPB was examined in 44 neonates undergoing CPB. Post-operative bleeding occurred in 36% and heparin rebound in 73%. Thrombin-initiated fibrin clot kinetic assay and partial thromboplastin time best assessed HPB.SummaryBackground Neonates undergoing cardiopulmonary bypass (CPB) are at risk of excessive bleeding. Blood is anticoagulated with heparin during CPB. Heparin activity is reversed with protamine at the end of CPB. Paradoxically, protamine also inhibits blood coagulation when it is dosed in excess of heparin. Objectives To evaluate heparin-protamine balance in neonates undergoing CPB by using research and clinical assays, and to determine its association with postoperative bleeding. Patients/Methods Neonates undergoing CPB in the first 30 days of life were studied. Blood samples were obtained during and after surgery. Heparin-protamine balance was assessed with calibrated automated thrombography, thrombin-initiated fibrin clot kinetic assay (TFCK), activated partial thromboplastin time (APTT), anti-FXa activity, and thromboelastometry. Excessive postoperative bleeding was determined by measurement of chest tube output or the development of cardiac tamponade. Results and Conclusions Of 44 neonates enrolled, 16 (36%) had excessive postoperative bleeding. The TFCK value was increased. By heparin in neonatal blood samples, but was only minimally altered by excess protamine. Therefore, it reliably measured heparin in samples containing a wide range of heparin and protamine concentrations. The APTT most closely correlated with TFCK results, whereas anti-FXa and thromboelastometry assays were less correlative. The TFCK and APTT assay also consistently detected postoperative heparin rebound, providing an important continued role for these long-established coagulation tests in the management of postoperative bleeding in neonates requiring cardiac surgical repair. None of the coagulation tests predicted the neonates who experienced postoperative bleeding, reflecting the multifactorial causes of bleeding in this population.
| S-EPMC6173634 | biostudies-literature
Project description:Introduction: Using a porcine model of accidental immersion hypothermia and hypothermic cardiac arrest (HCA), the aim of the present study was to compare effects of different rewarming strategies on CPB on need for vascular fluid supply, level of cardiac restitution, and cerebral metabolism and pressures. Materials and Methods: Totally sixteen healthy, anesthetized castrated male pigs were immersion cooled to 20°C to induce HCA, maintained for 75 min and then randomized into two groups: 1) animals receiving CPB rewarming to 30°C followed by immersion rewarming to 36°C (CPB30, n = 8), or 2) animals receiving CPB rewarming to 36°C (CPB36, n = 8). Measurements of cerebral metabolism were collected using a microdialysis catheter. After rewarming to 36°C, surviving animals in both groups were further warmed by immersion to 38°C and observed for 2 h. Results: Survival rate at 2 h after rewarming was 5 out of 8 animals in the CPB30 group, and 8 out of 8 in the CPB36 group. All surviving animals displayed significant acute cardiac dysfunction irrespective of rewarming method. Differences between groups in CPB exposure time or rewarming rate created no differences in need for vascular volume supply, in variables of cerebral metabolism, or in cerebral pressures and blood flow. Conclusion: As 3 out of 8 animals did not survive weaning from CPB at 30°C, early weaning gave no advantages over weaning at 36°C. Further, in surviving animals, the results showed no differences between groups in the need for vascular volume replacement, nor any differences in cerebral blood flow or pressures. Most prominent, after weaning from CPB, was the existence of acute cardiac failure which was responsible for the inability to create an adequate perfusion irrespective of rewarming strategy.
| S-EPMC9483155 | biostudies-literature
Project description:ObjectiveNeurologic complications seriously affect the survival rate and quality of life in patients with extracorporeal cardiopulmonary resuscitation (ECPR) undergoing cardiac arrest. This study aimed to repurpose selective hypothermic cerebral perfusion (SHCP) as a novel approach to protect the brains of these patients.MethodsRats were randomly allocated to Sham, ECPR, and SHCP combined ECPR (CP-ECPR) groups. In the ECPR group, circulatory resuscitation was performed at 6 minutes after asphyxial cardiac arrest by extracorporeal membrane oxygenation. The vital signs were monitored for 3 hours, and body and brain temperatures were maintained at the normal level. In the CP-ECPR group, the right carotid artery catheterization serving as cerebral perfusion was connected with the extracorporeal membrane oxygenation device to achieve selective brain cooling (26-28 °C). Serum markers of brain injury and pathomorphologic changes in the hippocampus were evaluated. Three biological replicates further received RNA sequencing in ECPR and CP-ECPR groups. Microglia activation and inflammatory cytokines in brain tissues and serum were detected.ResultsSHCP rapidly reduced the brain-targeted temperature and significantly alleviated nerve injury. This was evident from the reduced brain injury serum biomarker levels, lower pathologic scores, and more surviving neurons in the hippocampus in the CP-ECPR group. Furthermore, more differentially expressed genes for inflammatory responses were clustered functionally according to Kyoto Encyclopedia of Genes and Genomes pathway analysis. And SHCP reduced microglia activation and the release of proinflammatory mediators.ConclusionsOur preliminary data indicate that SHCP may serve as a potential therapy to attenuate brain injury via downregulation of neuroinflammation in patients with ECPR.
| S-EPMC9801244 | biostudies-literature
Project description:BackgroundGuidelines recommend evaluation for electrographic seizures in neonates and children at risk, including after cardiopulmonary bypass (CPB). Although initial research using screening electroencephalograms (EEGs) in infants after CPB found a 21% seizure incidence, more recent work reports seizure incidences ranging 3-12%. Deep hypothermic cardiac arrest was associated with increased seizure risk in prior reports but is uncommon at our institution and less widely used in contemporary practice. This study seeks to establish the incidence of seizures among infants following CPB in the absence of deep hypothermic cardiac arrest and to identify additional risk factors for seizures via a prediction model.MethodsA retrospective chart review was completed of all consecutive infants ≤ 3 months who received screening EEG following CPB at a single center within a 2-year period during 2017-2019. Clinical and laboratory data were collected from the perioperative period. A prediction model for seizure risk was fit using a random forest algorithm, and receiver operator characteristics were assessed to classify predictions. Fisher's exact test and the logrank test were used to evaluate associations between clinical outcomes and EEG seizures.ResultsA total of 112 infants were included. Seizure incidence was 10.7%. Median time to first seizure was 28.1 h (interquartile range 18.9-32.2 h). The most important factors in predicting seizure risk from the random forest analysis included postoperative neuromuscular blockade, prematurity, delayed sternal closure, bypass time, and critical illness preoperatively. When variables captured during the EEG recording were included, abnormal postoperative neuroimaging and peak lactate were also highly predictive. Overall model accuracy was 90.2%; accounting for class imbalance, the model had excellent sensitivity and specificity (1.00 and 0.89, respectively).ConclusionsSeizure incidence was similar to recent estimates even in the absence of deep hypothermic cardiac arrest. By employing random forest analysis, we were able to identify novel risk factors for postoperative seizure in this population and generate a robust model of seizure risk. Further work to validate our model in an external population is needed.
| S-EPMC8318326 | biostudies-literature
Project description:OBJECTIVES:We sought to define the lower and upper limits of cerebral blood flow autoregulation and the optimal blood pressure during cardiopulmonary bypass. We further sought to identify variables predictive of these autoregulation end points. METHODS:Cerebral autoregulation was monitored continuously with transcranial Doppler in 614 patients during cardiopulmonary bypass enrolled in 3 investigations. A moving Pearson's correlation coefficient was calculated between cerebral blood flow velocity and mean arterial pressure to generate the variable mean velocity index. Optimal mean arterial pressure was defined as the mean arterial pressure with the lowest mean velocity index indicating the best autoregulation. The lower and upper limits of cerebral blood flow autoregulation were defined as the mean arterial pressure at which mean velocity index was increasingly pressure passive (ie, mean velocity index ?0.4) with declining or increasing blood pressure, respectively. RESULTS:The mean (± standard deviation) lower and upper limits of cerebral blood flow autoregulation, and optimal mean arterial pressure were 65 ± 12 mm Hg, 84 ± 11 mm Hg, and 78 ± 11 mm Hg, respectively, after adjusting for study enrollment. In 17% of patients, though, the lower limit of cerebral autoregulation was above this optimal mean arterial pressure, whereas in 29% of patients the upper limit of autoregulation was below the population optimal mean arterial pressure. Variables associated with optimal mean arterial pressure based on multivariate regression analysis were nonwhite race (increased 2.7 mm Hg; P = .034), diuretics use (decreased 1.9 mm Hg; P = .049), prior carotid endarterectomy (decreased 5.5 mm Hg; P = .019), and duration of cardiopulmonary bypass (decreased 1.28 per 60 minutes of cardiopulmonary bypass). The product of the duration and magnitude that mean arterial pressure during cardiopulmonary bypass was below the lower limit of cerebral autoregulation was associated with the risk for stroke (P = .02). CONCLUSIONS:Real-time monitoring of autoregulation may improve individualizing mean arterial pressure during cardiopulmonary bypass and improving patient outcomes.
| S-EPMC5685671 | biostudies-literature