Major Neurological Dysfunction Research Articles

Abstract 15821: Patients With Amyloid Cardiomyopathy Who Receive Durable Mechanical Circulatory Support Are at Increased Risk for Mortality and Early Adverse Events

Introduction: Amyloid cardiomyopathy (ACM) is recognized increasingly as a cause of advanced heart failure. There are limited data describing clinical outcomes for ACM patients who receive durable mechanical circulatory support (MCS). Methods: This analysis included adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) with a primary diagnosis of dilated cardiomyopathy (DCM, N=19,921), non-amyloid restrictive cardiomyopathy (RCM, N=248), or ACM (N=48) who received durable MCS of any type or strategy from 2005-2017. We compared baseline characteristics and adverse events for the 3 groups. The primary endpoint was death with heart transplantation as a competing risk with follow-up censored at device explantation. Results: Patients with ACM (N=48) were older (61 y [IQR 55-69] versus 58 y [IQR 49-66] for DCM and 55 y [IQR 46-62] for non-amyloid RCM, P<0.001), and more likely to be male (85% versus 79% for DCM and 63% for non-amyloid RCM, P<0.001) and INTERMACS profile 1 (30% versus 18% for DCM and 21% for non-amyloid RCM, P=0.04) at implant. Use of biventricular support (concomitant left and right ventricular assist devices or total artificial heart) was highest in the ACM group (41% versus 7% and 19% for DCM and non-amyloid RCM groups, respectively, P<0.001). ACM patients experienced a higher frequency of major bleeding (48% versus 29% for DCM and 34% for non-amyloid RCM, P=0.005), neurologic dysfunction (22% versus 10% for DCM and 14% for non-amyloid RCM, P=0.006), and renal dysfunction (20% versus 10% for DCM and 17% for non-amyloid RCM, P<0.001) within 3 months. Risk of death at a median follow-up of 1 year was highest for the ACM group compared to DCM and non-amyloid RCM (Log-rank, P=0.014). Conclusion: Compared to DCM or non-amyloid RCM patients, those with durable MCS for ACM have the highest risk of early adverse events and lowest survival. These data highlight concerns with durable MCS for ACM.

End Stage Liver Disease Models and Outcomes in Pediatric Patients Supported with Short-Term Continuous Flow Ventricular Assist Devices

Purpose Short-term continuous flow VADs (STCF-VAD) are increasingly being utilized for mechanical support (MS) in the pediatric population. End-stage liver disease (ELD) models have been associated with mortality and morbidity in adult patients on MS. We sought to determine the relationship between outcomes in pediatric patients on STCF-VADs and 4 ELD models: MELD-XI, MELD-XI for those >1 year, PELD, and Pediatric MELD-XI (PMELD). Methods All pediatric patients supported with STCF-VADs, between June 2009 and December 2016 were included. Adverse outcomes, including major bleeding and neurological dysfunction were defined by PEDIMACs criteria. The MELD-XI, PELD, and PMELD score were calculated and their association with adverse events and a composite measure of death, major bleeding and neurological dysfunction was analyzed. Results Of 33 patients included, median age was 0.58 years (IQR 0.11-4.31), median weight was 8.0 kg (IQR 3.8-15.9), 52% had congenital heart disease, and 52% were male. For device strategy, 55% were on LVADs, 18% RVADs, and 24% BiVADs. In total, 76% patients experienced one of the 3 adverse events, with 76% experiencing a major bleed, 24% with neurological dysfunction, and 15% dying while on a STCF-VAD. The median MELD-XI score was 11.2 (IQR 9.4-29.9), MELD-XI (>1yr) 9.4 (IQR 9.4-22.9), PELD 6.0 (IQR 4.0-13.7) and PMELD -14.7 (IQR -18.8 - -12.2). A higher MELD-XI for all ages was significantly associated with death on device (31.52 vs. 10.24, p=.049) while a trend was seen for increased MELD-XI being associated with a major bleeding event (13.80, p=.054) and having any composite endpoint for all ages (13.80, p=.054). In addition, there was a trend towards a higher PMELD being associated with death (-12.87, p=.053). Lastly, there was no association with the models and any neurological events. Conclusion None of the ELD models were associated with neurological events. MELD-XI was significantly associated with death in patients of all ages and a trend can be seen with having a major bleeding event or any of the composite endpoints. These results suggest that ELD models may be limited in their ability to predict outcomes in this patient population. However, given the small patient numbers further work in a larger population are required to determine if the findings in this study hold true.

Neither Time in Therapeutic Range nor Most Recent International Normalized Ratio (INR) Correlate with Adverse Events in Patients Supported by Continuous-Flow Left Ventricular Assist Devices

Introduction Continuous-Flow Left Ventricular Assist Devices (CFLVADs) improve mortality and quality of life in end-stage cardiomyopathy patients. Adverse events however remain high. Hypothesis We hypothesize time in therapeutic range (TTR) correlates with adverse events compared to most recent INR. Methods The study group comprised of patients who suffered suspected/confirmed pump thrombosis, stroke or major bleeding event as defined by INTERMACS after ≥ 1 month at home with ≥ 1 month of INR values. Controls (CON) had at least 3 months of INR values after being home for 1 month from LVAD implant and who did not experience any adverse events (AE). Standard statistical methods were employed as indicated: Chi-square, Fishers Exact test, two-sample t-test, Wilcoxon Rank sum test, One way ANOVA and Kruskal Wallis Analysis. Patients with multiple adverse events were excluded. Results From June 2010 - December 2016, 132 patients underwent CFLVAD implantation at our institution who met entry criteria. Mean age was 57±13 yrs and 106 (80%) were male. Seventy-seven (58%) were implanted as bridge to transplant (BTT). There was no statistically significant difference in TTR (p=0.39, Table 1 ) or most recent INR (p=0.33, Table 2 ) prior to AE. Patients who suffered AEs were older than those who did not (59.3± 12 vs. 54.4±14.3 yrs, p=0.04). There was no association of AEs when stratified by gender, LVAD indication, LVAD device type, race, BMI or hospital length of stay (p=ns). Conclusions Neither time in therapeutic range nor most recent INR correlated with major bleeding, neurological dysfunction or pump thrombosis in CFLVAD patients in this analysis. Further investigation beyond strict INR control and anticoagulation is needed to reduce adverse events in this patient population.

Mitochondrial dysfunction is an important cause of neurological deficits in an inflammatory model of multiple sclerosis.

Neuroinflammation can cause major neurological dysfunction, without demyelination, in both multiple sclerosis (MS) and a mouse model of the disease (experimental autoimmune encephalomyelitis; EAE), but the mechanisms remain obscure. Confocal in vivo imaging of the mouse EAE spinal cord reveals that impaired neurological function correlates with the depolarisation of both the axonal mitochondria and the axons themselves. Indeed, the depolarisation parallels the expression of neurological deficit at the onset of disease, and during relapse, improving during remission in conjunction with the deficit. Mitochondrial dysfunction, fragmentation and impaired trafficking were most severe in regions of extravasated perivascular inflammatory cells. The dysfunction at disease onset was accompanied by increased expression of the rate-limiting glycolytic enzyme phosphofructokinase-2 in activated astrocytes, and by selective reduction in spinal mitochondrial complex I activity. The metabolic changes preceded any demyelination or axonal degeneration. We conclude that mitochondrial dysfunction is a major cause of reversible neurological deficits in neuroinflammatory disease, such as MS.

Biventricular Berlin Heart EXCOR Pediatric Use Across the United States

Biventricular assist device (BiVAD) support was a strong predictor of early mortality in the Berlin Heart EXCOR Pediatric investigational device exemption (IDE) study (Assess Safety and Probable Benefit of the EXCOR Pediatric Ventricular Assist Device [VAD]). In adults, it has been identified that 5% to 10% of the VAD population is benefited by BiVAD support over left ventricular assist device (LVAD) support. An analysis of the Berlin Heart study cohort was performed to characterize patients supported with BiVAD, examine risk factors of mortality in this group, and identify subsets of patients in whom BiVAD is associated with survival. All EXCOR Pediatric devices (Berlin Heart, Inc, The Woodlands, TX) placed in North America between May 2007 and December 2010 comprised the study cohort of 204 patients (128 [63%] LVADs and 76[37%] BiVADs). The following patient cohorts were analyzed to determine the effect of BiVAD use on survival: Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 patients, patients with abnormal bilirubin levels, patients who received previous extracorporeal membrane oxygenation (ECMO), and patients with a 10-mL pump size. There were more patients with BiVADs in INTERMACS profile 1 (63% compared with 46%; p=0.018). The incidence of major bleeding, neurologic and renal dysfunction, and infection was similar between BiVAD and LVAD groups. White race, abnormal glomerular filtration rate (GFR), sites with experience of less than 5 implantations, and use of 10-mL pumps were predictors of mortality in patients who received BiVADs. BiVADs were not associated with improved survival in any patient cohort; however, they were associated with increased mortality in patients who had undergone ECMO before receiving a VAD. BiVAD support was not associated with improved survival in any identified subset of patients. Although not randomized, these results (which were corrected for multiple possible risk factors) suggest that some children supported with BiVADs might have done better with LVADs alone. Further prospective studies will be needed to identify patient cohorts that will be better served with BIVAD support.

Neurocognitive long term follow-up study on drowned children

Aim of the studyReport cognitive and neurological outcome later in life of surviving drowned children who had received CPR either from bystanders or from emergency medical services (EMS) units. MethodsForty children who had drowned and admitted to pediatric intensive care unit after successful CPR between 1985 and 2007, were eligible for the study. Of those 21 gave a consent for neurological and neuropsychological examinations. All data are expressed as median (interquartile range). Mann-Whitley U, Wilcoxon signed ranks and Chi square tests were used. ResultsThe median age of the 21 patients at drowning was 2.4 (1.8, 5.5) years and 12.5 (8.6, 19.4) years at the time of neurological and neuropsychological examination. The median interval between the drowning accident and examinations was 8.1 (5.4, 14.4) years. Twelve patients (57.1%) had either signs of minor (6/21) or major neurological dysfunction (6/21). Eight subjects (40.0%) had full-scale intelligence quotient (FIQ) of less than 80 (range 20–78). The median estimated submersion time of the subjects with normal FIQ was 3.5 (2.0, 7.5)min, which was significantly shorter than for those with FIQ<80, 12.5 (5.0, 22.5)min (p=0.0013). Cognitive or neurologic deficits were detected in 17 of the 21 subjects, although 11 of them were reported to have a full recovery at the hospital discharge. ConclusionsThis study showed that 57% of the drowned and resuscitated children had neurological dysfunction and 40% a low FIQ. Neurological and neuropsychological long term follow-up in drowned children is highly recommended.

An unusual cause for recurrent jaundice in an otherwise healthy male

A 41-year-old Asian-Indian male presented with recurrent episodes of jaundice over the past six months. Physical examination was normal, barring mild icterus. Laboratory parameters revealed indirect hyperbilirubinemia. Further evaluation yielded a diagnosis of severe nutritional vitamin B12 deficiency. Indirect hyperbilirubinemia was ascribed to ineffective erythropoiesis. Underlying Gilbert's syndrome was ruled out by provocative testing with lipid-restricted diet. Presentation of severe vitamin B12 deficiency with isolated hyperbilirubinemia without concomitant major haematologic or neurologic dysfunction is unusual and potentially underdiagnosed. Awareness of this possibility can permit early diagnosis of vitamin B12 deficiency and forestall development of severe haematologic and neurologic sequelae.

Clinical Results of Ascending Aorta and Aortic Arch Replacement under Moderate Hypothermia with Right Brachial and Femoral Artery Perfusion

BackgroundSelective antegrade perfusion via axillary artery cannulation along with circulatory arrest under deep hypothermia has became a recent trend for performing surgery on the ascending aorta and aortic arch and when direct aortic cannulation is not feasible. The authors of this study tried using moderate hypothermia with right brachial and femoral artery perfusion to complement the pitfalls of single axillary artery cannulation and deep hypothermia.Materials and MethodsA retrospective analysis was performed on 36 patients who received ascending aorta or aortic arch replacement between July 2005 and May 2010. The adverse outcomes included operative mortality, permanent neurologic dysfunction and temporary neurologic dysfunction.ResultsOf these 36 patients, 32 (88%) were treated as emergencies. The mean age of the patients was 61.9 years (ranging from 29 to 79 years) and there were 19 males and 17 females. The principal diagnoses for the operation were acute type A aortic dissection (31, 86%) and aneurysmal disease without aortic dissection (5, 14%). The performed operations were ascending aorta replacement (9, 25%), ascending aorta and hemiarch replacement (13, 36%), ascending aorta and total arch replacement (13, 36%) and total arch replacement only (1, 3%). The mean cardiopulmonary bypass time was 209.4±85.1 minutes, and the circulatory arrest with selective antegrade perfusion time was 36.1±24.2 minutes. The lowest core temperature was 24±2.1℃. There were five deaths within 30 post-op days (mortality: 13.8%). Two patients (5.5%) had minor neurologic dysfunction and six patients, including three patients who had preoperative cerebral infarction or unconsciousness, had major neurologic dysfunction (16.6%).ConclusionWhen direct aortic cannulation is not feasible for ascending aorta and aortic arch replacement, the right brachial and femoral artery can be used as arterial perfusion routes with the patient under moderate hypothermia. This technique resulted in acceptable outcomes.

The Groningen ART cohort study: ovarian hyperstimulation and the in vitro procedure do not affect neurological outcome in infancy

Due to the growing number of children born following assisted reproduction technology, even subtle changes in the children's health and development are of importance to society at large. The aim of the present study was to evaluate the specific effects of ovarian hyperstimulation and the in vitro procedure on neurological outcome in 4-18-month-old children. In this prospective assessor-blinded cohort study, we included singletons born following controlled ovarian hyperstimulation in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (COH-IVF; n = 68) or modified natural cycle-IVF/ICSI (MNC-IVF; n = 57) or naturally conceived singletons of subfertile couples (NC; n = 90). Children were assessed with standardized, age-specific and sensitive neurological assessments (TINE and Hempel assessment) at 4, 10 and 18 months. Neurological examination resulted in a neurological optimality score (NOS), a fluency score and a clinical neurological classification. Fluency of movements is easily affected by neurological dysfunction and is therefore a sensitive measure for minimal changes in neuromotor development. The NOS and the fluency score were similar in COH-IVF, MNC-IVF and NC children. None of the children showed major neurological dysfunction and rates of minor neurological dysfunction at the three ages were not different between the three conception groups. We found no effects of ovarian hyperstimulation or the in vitro procedure itself on neurological outcome in children aged 4-18 months. The findings of our study are reassuring, nevertheless it should be kept in mind that subtle neurodevelopmental disorders may emerge when children grow older. Continuation of follow-up in older and larger groups of children is therefore still needed.

Non-infective morbidity in diabetic patients undergoing coronary and heart valve surgery

Studies of postoperative morbidity in diabetics have focussed on infection; however, autonomic and cardiovascular complications of diabetes potentially increase the risk for non-infective morbidity. We sought to investigate major non-infective early postoperative complications in diabetic patients. We identified diabetics who underwent CABG and/or valve operation from 1998 through 2007, and compared their clinical characteristics and outcome with a contemporaneous cohort of non-diabetic patients. The demographic characteristics of 1145 diabetics were similar to 5534 non-diabetic patients (mean age 66+/-9 years vs 66+/-10 years, p=0.45, female 27.5% vs 26.7%, p=0.59, respectively). Class III/IV angina symptoms (43.9% vs 34.9%, p<0.0001), intravenous nitrates therapy (10.4% vs 6.6%, p<0.0001), heart failure (24.8% vs 20.4%, p=0.001), prior myocardial infarction (37% vs 31%, p<0.0001), ejection fraction </=0.50 (34.5% vs 23.0%, p<0.0001), triple vessel disease (66.3% vs 54.8%, p<0.0001), renal insufficiency (3.6% vs 1.5%, p<0.0001) and peripheral vascular disease (16.1% vs 8.7%) were prevalent amongst diabetics. The predominant operation was CABG (diabetic 84.8% vs non-diabetic 73.9%). Low cardiac output (28.3% vs 24.0%, p=0.002), renal dialysis (2.0% vs 0.8%, p<0.0001) and cerebrovascular events (5.1% vs 3.8%, p=0.04) more often complicated recovery of diabetic patients, but operative mortality was similar for both groups. However, postoperative myocardial infarction was less common in diabetics (0.5% vs 1.4%, p=0.02). Diabetes was not a risk factor for the composite endpoint of major non-infective morbidity and operative mortality (OR 1.15, 95% CI 0.97-1.37, p=0.10). Diabetic patients were prone to longer postoperative hospitalisation (9.7+/-10.5 days vs 8.4+/-6.7 days, p<0.0001) and discharge to a convalescence facilities (9.8% vs 6.9%, p<0.0001). Diabetic patients present for surgery with higher prevalence of cardiovascular risk factors and are more likely to develop major non-infective complications, including cardiac, renal and neurological dysfunction, even though diabetes does not directly influence non-infective postoperative morbidity following CABG and/or valve operations.

Preditores de disfunção neurológica maior após cirurgia de revascularização miocárdica isolada

OBJETIVO: Avaliar a incidência e os fatores preditores de disfunção neurológica maior pós-operatória e a evolução clínica precoce em uma coorte não selecionada. MÉTODO: Um total de 1760 pacientes consecutivos submetidos a CRM isolada, no Hospital São Lucas da PUCRS, entre janeiro de 1997 e fevereiro de 2004, foram incluídos. Dados demográficos, informações do procedimento e desfechos perioperatórios foram coletados usando-se o protocolo do registro de dados da Unidade de Pós-Operatório de Cirurgia Cardíaca do nosso hospital. As variáveis consideradas estatisticamente significativas foram aquelas com p <0,05 e intervalo de confiança de 95%. RESULTADOS: Na nossa amostra, 52 (3%) pacientes evoluíram com disfunção neurológica maior (AVC). Na análise univariada, idade avançada, maior prevalência de doença pulmonar obstrutiva crônica (DPOC), doença cerebrovascular (DCV) prévia, média de fibrinogênio elevada, desenvolvimento de choque ou hipotensão grave, presença de taquicardia supraventricular (fibrilação atrial ou flutter), ocorrência de síndrome da resposta inflamatória sistêmica (SIRS) e ventilação mecânica prolongada estiveram associados ao desenvolvimento de AVC. Na análise multivariada, a história prévia de DCV e DPOC demonstraram ser preditores independentes para a ocorrência de disfunção neurológica maior. Ventilação mecânica prolongada também apresentou associação independente com o desfecho. Além disso, a ocorrência de AVC aumentou significativamente o tempo de internação hospitalar e a mortalidade intra-hospitalar. CONCLUSÃO: A disfunção neurológica permanece sendo relevante causa de morbidade hospitalar, no pós-operatório de CRM com circulação extracorpórea.

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Two distinct forms of minor neurological dysfunction: perspectives emerging from a review of data of the Groningen Perinatal Project

Two distinct forms of minor neurological dysfunction: perspectives emerging from a review of data of the Groningen Perinatal Project

Antenatal predictors of the neurologic sequelae at 3 years of age:: a multivariate analysis

Objective: To study the association between fetal blood flow abnormalities and the occurrence of long-term neurologic sequelae. Study design: Umbilical, aortic and middle cerebral artery blood flow parameters were obtained by Doppler examination and retrospectively analyzed in 128 high-risk singleton pregnancies, followed by neurologic examination of the surviving children at 3 years of age. Traditional parameters of neurologic outcome (Apgar scores, intrauterine growth retardation (IUGR), umbilical artery pH and base deficit, gestational age, birth weight, newborn encephalopathy, mode of delivery, fetal heart rate, neurosonographic examination) were included as possible confounding factors. Mann–Whitney U-test, Student’s t-test, analysis of variance or Fisher’s exact test, where applicable, were used for the univariate analysis. A stepwise logistic regression procedure was conducted to test the independent association of selected perinatal risk factors on neurological outcome. Statistical significance was assumed at P<0.05. Results: Eighteen out of 114 surviving children suffered neurologic illness at 3 years of age. Four children had major neurologic dysfunction and the remaining 14 suffered minor or mild form of the disease. Although blood flow parameters and various perinatal parameters did not differ significantly between the group of children with major neurologic dysfunction and healthy children, aortic resistance index showed an independent association with occurrence of minor or mild neurologic disabilities. Conclusion: Antenatal evaluation of the aortic blood flow might be an important predictive variable for permanent neurologic disturbances.

Obesity and coronary artery surgery

Objective: To assess whether obesity is a risk factor for morbidity and mortality in patients undergoing elective coronary artery revascularization. Design: Prospective, clinical study. Setting: University hospital. Participants: Three hundred forty-five consecutive patients who underwent elective coronary revascularization with cardiopulmonary bypass and without associated procedures. Interventions: Patients were assigned to the obese group if their body mass index was greater than 30 for men and 28.6 for women, according to the World Health Organization indications. Measurements and Main Results: Preoperative and intraoperative variables were collected and checked for homogeneity of the groups. Postoperative outcome was assessed on the basis of intubation time, intensive care unit (ICU) and postoperative hospital stay, mortality rate, and incidence of transfusions, reoperations, low-output syndrome, minor and major neurologic dysfunction, minor and major lung dysfunctions, renal dysfunction, and superficial and deep infections. The effect of obesity on postoperative outcome was tested with a multivariate logistic regression analysis. Obese and control patients had the same intubation time and ICU and postoperative hospital stay. Mortality and all major complications occurred with the same incidence in the two groups. Obese patients had a significantly ( p < 0.05) greater rate of superficial infections and more (24.1% v 7.4%; p < 0.001) minor lung complications. Conversely, they had a significantly lower transfusion rate (27.5% v 42.7%; p < 0.01). Conclusion: Obese patients had only minor complications after coronary artery surgery. The large body surface area because of obesity protects them against the hemodilutionrelated transfusion risk.

Pupillary signs during cardiac surgery. Their use in the prediction of major cerebral deficit following cardiopulmonary bypass.

Pupil sizes and reactions to light were studied in 100 patients who had cardiopulmonary bypass. Behaviour of the pupils was observed at six stages during the operation. Most patients (71) had pupils of equal size and similar reaction to light at all times. Twenty-three patients developed unequal pupils at some stage, while six had equal pupils throughout but exhibited differing reaction to light. Major cerebral deficit was significantly more common after operation in patients who developed inequality in pupil size than those who did not (p less than 0.05). No relationship was seen between dissimilar pupil reaction to light and the development of neurological complications. The clinical estimation of pupil size may help to identify those patients who may exhibit postoperative major neurological dysfunction.

Epidemiology of Infantile Hydrocephalus in Sweden

The aetiology of infantile hydrocephalus (IH) was studied in a population-based series of 141 children with IH, born at term in southwestern Sweden 1967-82. A prenatal aetiology was present in 81 children (57%), a pre- and perinatal in 6 (4%), a perinatal in 27 (19%), and a postnatal in 8 (6%); the origin in 19 children (13%) remained untraceable. A variety of aetiologies were revealed or indicated among prenatal conditions. The dominant intrauterine infection was toxoplasmosis. The predominant perinatal condition was posthaemorrhagic IH. The broad outline of outcome differed between pathogenetic groups. Children with a clear prenatal onset of IH were found to be at high risk for early death or multiple neurological impairments. Thirteen of 63 (21%) within this group had died before 2 years of age and 34 of the 50 (68%) survivors showed major neurological dysfunction. This contrasted to the incidences of 3% deaths and 30% sequelae in children with IH of other onset.

Epidemiology of Infantile Hydrocephalus in Sweden

The aetiology of infantile hydrocephalus (IH) was studied in a population-based series of 61 children with IH born 1967-82 at less than 37 weeks of gestation. A prenatal origin was present in 17 children (28%), a pre- and perinatal in 17 (28%), a perinatal in 26 (43%) and a postnatal in one (1%). The predominant single cause was postaemorrhagic IH, which was diagnosed in 19 (31%). In addition, an undiagnosed cerebral haemorrhage was considered to be the cause in another 25%. The outcome differed between pathogenetic groups. Children with a clear onset of IH (pre-, peri- or postnatal) were found to be at high risk for early death or multiple impairments. Sixteen of 39 (41%) within these groups had died before 2 years of age and 18 of the 23 (78%) survivors showed major neurological dysfunction. This contrasted to no mortality and 41% major dysfunction in children with a less clear onset of IH. A new subgroup consisting of infants born before 28 weeks of gestation emerged in the early 1980s. All infants with IH in this group developed a severe multihandicap condition.

Prevention of major perioperative neurological dysfunction—a personal perspective

Neurological dysfunction following cardiac surgical procedures has many causes. We have reduced perioperative neurological dysfunction to very low levels with protocols related to five potential causes of perioperative stroke. The five areas we have concentrated upon are: 1) components and use of the heart-lung machine; 2) air embolization; 3) intrinsic cerebrovascular disease; 4) atheroemboli from the ascending aorta and; 5) clot emboli from the left ventricle. We have employed methods of operation of the heart-lung machine which minimize the risk of microemboli or air emboli. Air evacuation manoeuvres are employed in every patient at the termination of cardiopulmonary bypass. A brain protection protocol which employs pharmacological brain protection, as well as increased oxygen-carrying capacity and perfusion pressure, is used in patients with cerebrovascular disease and patients with atheromatous ascending aorta. Applying these protocols, we have performed 690 consecutive cardiac surgical procedures with strokes occurring in three patients (0-4%). There was one stroke in 558 patients (0.2%) having coronary artery bypass grafting. Stroke occurred in one of 48 high risk patients (2%) in whom the brain protection protocol was used. There were no apparent episodes of air embolization or embolization of clot from the left ventricle.