Brain Injury and Protection During Heart Surgery

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Patients were normothermic with continuous blood heating at All patients underwent general anesthesia with endotracheal intubation according to a local protocol, with the use of etomidate and fentanyl at induction, muscle relaxation with pancuronium, and maintenance of anesthesia with sevoflurane and fentanyl. The standard cold crystalloid intermittent cardioplegic solution type St Thomas II was used. The de-airing procedures after restarting the heart were conducted with vent suction from the left atrium and ascending aorta under the control of TEE. Effort was undertaken to check for any residual air during the de-airing procedures, and the de-airing time was precisely planned to ensure cessation of any additional air bubbles from the pulmonary veins.

All operations were performed by the same surgeon. Chest tubes were removed on postoperative day 1 or 2. Distal lumen was occluded with a typical Luer stopper. The perforated part of the drain tube was fixed with two sutures to the left side of the pericardium just below the left branch of the retractor and covered with gauze. The flow of CO 2 was measured with a standard flowmeter for medical CO 2.

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An increase in the partial pressure of CO 2 , consequent decrease in the pH and BE, was corrected by the perfusionist with a minimal increase in the volume of air added to the gas exchanger. The first 10 mL of blood sample P1 was taken just after induction, intubation, and installation of the central venous line. The next sample P2 was taken in the postoperative unit 2 hours after de-clamping of the aorta.

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The third sample P3 was collected 24 hours after operation. For continuous variables with a normal distribution in the Kolmogorov—Smirnov test, the two-sample t -test was used. For the continuous variables without normal distribution, the Mann—Whitney U test for independent data samples and the Wilcoxon signed-rank test for correlated data samples were used.

The second patient from the opposite group was matched automatically.

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The statistical analysis was performed using the licensed Statistica There were 49 patients in the treatment T group 23 women and 26 men, aged 41—77 years [mean In the control C group, there were 51 patients 22 women and 29 men, aged 45—79 years [mean The demographic and preoperative data are presented in Table 1. The postoperative data and complications are summarized in Table 3.

Table 1 Demographic data Notes: a Chi-squared test. Table 2 Procedures and intraoperative data Notes: a Chi-squared test. Similar results were observed in the study group 1. In the older patients in the treatment and control groups, the differences were not significant Table 7. Abbreviation: NS, not significant.

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In the older group with TVA, results were significantly higher than in the younger group 1. The only direct evidence that CO 2 flooding could be effective was found when comparing the SB results between younger patients in the study and control groups without TVA. In the second measure, 2 hours after surgery, we also found significant differences 0. This might have been caused by increased suction from the operating field since the application and tying of sutures to the tricuspid ring are performed after aortic cross-clamp release and the blood, which flows from the coronary sinus, requires intensive suction for a period of 10—20 minutes.

This difference in the results of both groups with and without TVA made us realize the mistake of not including a proportional distribution of patients with TVA in our randomization assumptions. The important problem of finding a way to effectively replace air with CO 2 in the operating field has been addressed by several clinical trials that established the principles of operating field insufflation offering an appropriate concentration of CO 2 in the heart chambers in order to make sure that residual microbubbles of gas are largely filled with CO 2. Yet, whether the method is legitimate or not remains an open question.

Microbubbles of air reach cerebral circulation during virtually all of cardiac surgery procedures.

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Although their number increases considerably when opening the chambers of the heart, they do not cause measurable symptoms and it is impossible to detect consequences of microembolism using typical neurological tests. Several studies demonstrated a correlation between small lesions in the brain detected on an magnetic resonance imaging MRI scan and neurological tests, but other studies have not confirmed these observations.

Some authors were of the opinion that when comparing patients a few months after a cardiac procedure, neurological behavioral changes appear more often in patients after CABG than in patients after OPCAB, but these associations were denied by others. Haggag et al 27 have shown, in a study performed on rats, that injection of air into the arterial system does not cause lesions typical for microembolism. Neville et al, 28 in a study comparing valve procedures with CABG, also did not find differences in the frequency of postoperative neurological dysfunction between the two groups, despite detecting much more air in carotid arteries on ultrasonography during valve procedures.

In contrast, Herrmann et al 29 have shown that operations involving opening of the heart chambers result in a higher percentage of neurological dysfunctions and a higher increase in brain damage biomarkers in comparison to CABG. Martens et al 30 examined the influence of delivering air and CO 2 to the carotid arteries of pigs on the occurrence of lesions on an MRI scan and concluded that air caused extensive cerebral infarction while CO 2 did not cause any lesions that would be detectable with MRI.

However, it must be underlined that a large amount of air reaching cerebral arteries during a cardiac surgery may only be a result of technical error. Our study is not without limitations. Second, the study reports laboratory findings, without a clinical postoperative perspective. The postoperative dementia screening Mini Mental State Examination [MMSE] or a detailed neurocognitive examination during the follow-up period would provide an important insight into the effect of CO 2 flooding on neurological outcome. Third, the number of patients included in the study is relatively small and further research might be required to eliminate sample size effect.

Fourth, although elevated serum SB levels after cardiac operations with CPB are sensitive and specific for ischemic stroke, its appearance in surgical patients without neurological injury and its potential release from extracranial sources ie, adipocytes, chondrocytes, and melanocytes make its use as a postoperative biomarker of neurological insult debatable.

Serum biomarkers of neurologic injury in cardiac operations. Ann Thorac Surg. Coronary and other air embolization occurring during open cardiac surgery; prevention by the use of gaseous carbon dioxide. Retained intracardiac air. Transesophageal echocardiography for definition of incidence and monitoring removal by improved techniques. J Thorac Cardiovasc Surg. Neurocognitive complications after coronary artery bypass surgery. Ann Neurol. Flooding the surgical field with carbon dioxide during open heart surgery improves segmental wall motion. J Extra Corpor Technol. Carbon dioxide field flooding minimizes residual intracardiac air after open heart operations.

An effective method of replacing air in the chest with CO2 during open-heart surgery. Severe hypercarbia during cardiopulmonary bypass: a complication of CO2 flooding of the surgical field. Anesth Analg. Lippmann M. Complications of CO2 flooding the surgical field in open heart surgery: an old technique revisited. Barnard J, Speake D. In open heart surgery is there a role for the use of carbon dioxide field flooding techniques to reduce the level of post-operative gaseous emboli?

Interact Cardiovasc Thorac Surg. Giordano S, Biancari F. Does the use of carbon dioxide field flooding during heart valve surgery prevent postoperative cerebrovascular complications? Optimal carbon dioxide application for organ protection in cardiac surgery. Efficiency of a gas diffuser and influence of suction in carbon dioxide deairing of a cardiothoracic wound cavity model. Carbon dioxide field flooding versus mechanical de-airing during open-heart surgery: a prospective randomized controlled trial.

Magnetic resonance imaging and neuropsychological changes after coronary artery bypass graft surgery: preliminary findings. J Neurosurg Anesthesiol. Diffusion- and perfusion-weighted magnetic resonance imaging of the brain before and after coronary artery bypass grafting surgery. Cerebral ischemic lesions on diffusion-weighted imaging are associated with neurocognitive decline after cardiac surgery. Brain microemboli associated with cardiopulmonary bypass: A histologic and magnetic resonance imaging study. Subclinical cerebral complications after coronary artery bypass grafting: prospective analysis with magnetic resonance imaging, quantitative electroencephalography, and neuropsychological assessment.

The purpose of the present prospective study was to determine the incidence of brain damage in patients undergoing elective CABG using conventional and diffusion-weighted MRI and neuropsychological testing before surgery, at the time of hospital discharge and 3 months after surgery. The relation between radiological data and clinical and surgical variables and neuropsychological test performance was analyzed. A total of 35 patients with coronary heart disease undergoing elective CABG gave their informed consent and were enrolled in the study. Patients who had a history of hemodynamically relevant cerebrovascular disease, psychiatric illness, previous cardiac operation or concomitant valvular disease, renal insufficiency i.

All patients were non-emergent and awaited operation on the regular surgery ward. Patients were studied at three points in time: before operation base line, examination 1 [E1] , early before discharge E2 , and 3 months after operation E3. A physical examination, neurological examination, neuropsychological testing and a MRI scan of the brain were performed preoperatively and postoperatively in all 29 patients who completed the 3-month follow-up investigation.

Cognitive brain function was assessed using a well-validated battery of 13 standardized psychometric tests including two questionnaires. All tests were performed by the same investigator who was an experienced neuropsychologist. To minimize learning effects the tests existed in parallel forms and were randomly assigned to the respective examination.

The testing comprised the assessment of performance in five major cognitive domains known to be vulnerable to organic injury: attention, rate of information processing, memory and verbal learning, ability of logical thinking, and visual-spatial perception. The affective status of the patients was assessed with the use of standardized questionnaires on depression and mood. To measure the patient's attention and psychomotor speed Reitan's Trail making test version B TMB and Zimmermann's divided attention test were administered.

Reitan's Trail making test version A was used to measure the speed of information processing. The digit span subtest of the Wechsler Memory Scale—Revised was further used to test short-term digit span forward and working memory for verbal material digit span backward. The verbal learning test was used to test the ability of learning verbal material and to recall it immediately word list immediate and after a min delay word list delayed. The Corsi block tapping test investigates the memory of spatial structures and exists in two forms Corsi block tapping forward and backward. In addition to the psychometric tests, the patients were asked to fill in questionnaires on mood von Zerssen's Bf-S', 28 items and depression general depression scale—short version, 15 items, modified from hospital anxiety and depression scale-short version.

In both questionnaires a lower score indicates a lower level of depression and discontent. Clinical examination was carried out by an experienced neurologist before surgery, early before discharge, on the day of 3-month follow-up evaluation and in between, when necessary. The examination consisted of a medical history, physical examination and detailed neurological examination.

By 3-month evaluation, neurological examination, neuropsychological testing and brain MRI were obtained on the same day of visit. Field of view was mm for all sequences. Slice thickness was 6 mm for turbo—spin—echo sequences and 5 mm for diffusion-weighted sequence. Images were evaluated by consensus of two experienced neuroradiologists using standardized evaluation forms.

The presence of previous brain abnormalities, localization and volume of new lesions were recorded. On looking for the presence of any new brain lesion on postoperative MRI scans, the investigators were blind to the patient's individual postoperative course and the baseline status. For volumetry, the images were magnified fourfold, the area of lesion was delineated manually in each image slice and the volume was calculated using standard scanner software.

CABG was performed with standard anesthesia techniques and surgical procedures. Ethmidate, sufentanyl and rocuronium were administered intravenously as needed to induce general anesthesia and isofluran to maintain it. CPB was established by aortic and single venous cannulation. Aortic side clamping was performed for fashioning proximal anastomoses.

Cardiac arrest was achieved by applying cold Bretschneider cardioplegia solution through a cardioplegia cannula. Arterial partial pressure of carbon dioxide p a CO 2 was maintained at 35—40 mmHg and the arterial tension of oxygen was maintained at — mmHg during CPB. Non-pulsatile blood flow during CPB was maintained at 2. Mean arterial pressure was kept higher than 50 mmHg throughout the operation with vasoactive agents when necessary. Heparin was added to the heart-lung machine to achieve an activated clotting time above s during CPB.

A P -value below 0. All variables were tested for normal distribution with the Kolmogorov Smirnov-1 sample test. Differences of neuropsychological variables between the three times of testing were analyzed with repeated measures univariate analysis of variance and the Friedman test, respectively. For comparison of two group means, Student's t -test and Wilcoxon test were used, respectively. The relation between demographic and clinical variables e. In order to analyze whether cognitive dysfunction at the 3-month follow-up examination was related to new ischemic MRI lesions, a two-step analysis was performed: 1 the unpaired Student's t -test was calculated between patients with and without new MRI lesions for the respective neuropsychological variable, 2 in case of a significant difference between the two subgroups, a regression analysis was administered.

Thirty-five patients underwent CABG and participated in the prospective study. Six patients dropped out of the study postoperatively because of the following reasons: one patient died within 24 h after surgery, one had CABG without CPB, one sustained a major middle cerebral artery infarction on postoperative day 3 with hemiparesis and aphasia, two refused to comply at the 3-month follow-up investigation and one had postoperative renal failure and pneumonia requiring long-term ventilation.

Finally, the study population consisted of 29 patients who completed all preoperative and postoperative examinations including the 3-month follow-up study. There were 5 women and 24 men with a mean age of The preoperative neuropsychological testing was performed 3.

The first postoperative neuropsychological testing was performed 5. Duration of extracorporeal circulation was Table 1 shows the most relevant demographic, clinical and perioperative data of the study group. There was no statistical difference between the two subgroups of patients with and without new lesions on postoperative MRI. There was no evidence of major focal neurological abnormalities on serial examinations following CABG in the 29 patients. These patients underwent neurocognitive testing at the time of full recovery from the episodic symptoms as considered by a neurologist.

Five patients had 1 new lesion, 7 patients had 2—4 lesions, and 1 patient had 7 lesions. There were 32 new focal lesions, 18 in the left hemisphere and 14 in the right. The lesions were rounded and their volume was small ranging from Most of the lesions were supratentorial with 10 lesions in the frontal lobe, 9 in the parietal, 7 in the occipital and 1 lesion in the temporal lobe.

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Three of the four infratentorial lesions were in the cerebellum. The greatest single new lesion was found in a year-old patient without overt neurological abnormalities on serial postoperative examinations Fig. Preoperative Doppler sonography showed plaques in the carotid arteries on both sides but no stenosis, and preoperative brain MRI was normal. The patient was discharged from hospital on postoperative day 4 after an uneventful course.

In all five patients with more than three lesions, the abnormalities were dispersed in different cerebral artery territories. No brain abnormalities were seen on the preoperative scan. Postoperative MRI disclosed a focal discrete area of increased signal in the left lower cerebellar hemisphere. The lesion was interpreted as indicative of a small ischemic brain injury secondary to embolization.

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Table 2 summarizes the scores for the neuropsychological tests before and after CABG. As compared to baseline performance most of the patients exhibited a deterioration in attention early postoperatively Fig. By 3 months postoperatively, the function of attention had recovered Fig.

This is expressed in the mean TMB scores which increased from The scores in depression and mood were also increased early postoperatively Table 2 pointing out that the affective condition of the patients was markedly impaired few days after CABG. At the 3-month follow-up examination, 3 of the 4 tests with cognitive decline early postoperatively and both depression and mood scores returned to their baseline values.

However, the test score for verbal learning ability decreased from The individual performance in verbal learning ability is shown in Fig. Trail making test B measuring attention and psychomotor speed. Arrows indicate the difference in individual test score between the different testing points. The score at baseline examination was set to zero.

Downward arrows mean a decrease in function and vice versa. Word list test measuring individual verbal learning ability. There was no statistical correlation between the presence of new brain lesions on MRI and persistent verbal learning deficit at the 3-month follow-up examination Fig. None of the clinical variables e. There was also no association between clinical factors and new postoperative MRI lesions multivariate analysis using a multiple linear regression analysis, Table 1. Individual performance in the word list test in patients with and without new lesions on postoperative MRI.

In the present prospective study on 29 patients undergoing elective CABG, neurocognitive function was markedly impaired postoperatively. The deficits pertained to major cognitive domains such as attention, memory and executive functions, but usually resolved within weeks. However, verbal learning ability remained deteriorated even after 3 months. There was no significant correlation between the presence of new brain lesions and the persistent neurocognitive dysfunction 3 months after operation. Advances in modern cardiac surgery over the past 2 decades have resulted in a relatively low mortality and cardiac morbidity.

Nevertheless, cardiac surgery may be associated with adverse neurological and neuropsychological outcome.

Key points

Clinically recognized cerebral infarction occurs in 0. More subtle postoperative changes in cognitive function as detected by a decline in neuropsychological testing scores from baseline are considerably more common. In some patients, longer-term cognitive dysfunction is reported to be present 1—5 years after operation [1 , 3].

The relatively high prevalence and persistence of postoperative cognitive decline is of particular importance since it may result in decrease in quality of life and work performance [2]. The frequency of postoperative neuropsychological impairment and the pattern of early decline and late recovery in this study is in line with numerous studies [1 , 3 , 17]. Significant cognitive decline had occurred early postoperatively in three cognitive domains. By 3 months, most of these deficits had recovered to baseline in most patients, but verbal learning ability was still severely deteriorated.

Longitudinal assessment of cognitive function needs to be awaited to determine the significance of this impairment on long-term outcome of patients.

Closure of left atrial appendage during heart surgery protects the brain (LAACS)

The cause of postoperative cognitive dysfunction is yet unknown, and particularly cognitive decline years after operation is subject to much debate. It may represent the effect of age in patients with underlying neurological disease, or it may be the result of subtle brain injury at the time of coronary surgery [15]. Further long-term studies with patients undergoing CABG compared to patients with coronary disease without CABG as a control group treated either medically or by percutaneous coronary intervention are required to provide answers to these questions.

Many different methods have been used as potential sensitive indicators of cerebral injury associated with heart surgery. Because of its superiority to other imaging methods, MRI has been increasingly employed in the study protocols before and after open heart surgery. In a larger series of Vanninen et al. No patient experienced major neurological complications and there was no significant deterioration in mean cognitive performance 3 months after surgery.

For the detection of ischemia, new MRI technology with diffusion-weighted sequences is more sensitive than T2-weighted images [18] , but studies using DWI are yet scanty. Bendszus et al. Similarly, Restrepo et al. The correlation of the presence of new MRI lesions with postoperative neurocognitive decline is variable in the few studies that have assessed cognition. Some investigations report that the new MRI lesions were associated with neurocognitive decline [10 , 14 , 15]. In the series of Restrepo et al. Other clinical characteristics were similar between patients with and without new DWI lesions, including stroke risk factors [15].

In contrast, other studies, including our own, failed to find an association between the presence of new postoperative lesions and neuropsychological decline [11 , 13]. In the present study, this was even true when cognitive decline was persistently impaired 3 months after operation. Despite a good interobserver agreement for the detection of new diffusion lesions on postoperative scans, we cannot preclude an overestimation of subtle areas of hyperintensity particularly in patients with preexisting cerebral vasculopathy.

Since the new lesions are also visible on T2-weighted images, there is evidence of structural brain damage. The discrepancy between the presence of new MRI lesions and the absence of clinically overt neurological deficits prompts the proposal that the severity of brain damage is limited. It may be hypothesized, however, that new postoperative lesions result in subtle brain injury that will leave patients more susceptible to cognitive decline from degenerative or atherosclerotic disease years later.

Larger series are required to determine the significance of postoperative brain abnormalities with regard to neurological and neuropsychological long-term outcome of patients. The pathogenesis of new ischemic brain injury after CABG is unknown. Possible underlying mechanisms are embolization and hypoperfusion [5 , 8 , 20—22]. From the pattern of distribution, most of the MRI lesions in the present study are considered embolic even though hypoperfusion-induced border zone edema and small infarcts may not be precluded in a few cases.

Emboli are made of gas, thrombi, fragments of atheromatous plaques from the ascending aorta, cell aggregates, fat or inorganic debris from the bypass circuit tubing [6]. The sensitivity of diffusion-weighted MRI is limited by the spatial resolution. Lesions smaller than the pixel size are hardly to detect. Microbubble emboli would produce diffuse cerebral hypoxemia with cytotoxic edema resulting in a reduced attenuated diffusion coefficient on magnetic resonance spectroscopy [13].

Brain Injury and Protection During Heart Surgery Brain Injury and Protection During Heart Surgery
Brain Injury and Protection During Heart Surgery Brain Injury and Protection During Heart Surgery
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Brain Injury and Protection During Heart Surgery Brain Injury and Protection During Heart Surgery
Brain Injury and Protection During Heart Surgery Brain Injury and Protection During Heart Surgery

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