Risk Factors For Neurologic Injury Research Articles

Perioperative genomics and neurologic outcome: we can’t change who we are

Adverse cerebral outcomes have been described in most perioperative settings; however, for quite some time, cardiac surgery has been the poster child for cognitive dysfunction as well as incrementally severe complications, such as delirium, encephalopathy and stroke. Not that these complications do not occur in other operative settings, but with the incidence of post-cardiac surgery complications being generally higher than in other settings, cardiac surgery patients are an easily identifiable group to study in detail. Understanding the factors that influence perioperative cerebral outcome has never been more relevant, as not only are patients presenting for surgery at an increasingly older age (i.e., consistent with global demographic changes) but they frequently have multiple co-morbidities (many of which are risk factors for neurologic injury). Despite changes in the management of coronary artery disease (CAD) that have lead to a gradual decline in these procedures over the past 5–10 years, coronary artery bypass graft surgery (CABG) remains one of the most commonly performed operations. Furthermore, a recent large-scale study identified that the optimal management of multivessel CAD was with CABG, as opposed to percutaneous intervention. This may lead to a resurgence of CABG surgery with a further increase in the overall number of patients manifesting neurologic dysfunction. Much has been written about the risk factors for adverse neurologic outcome. Although many factors are modifiable, such as the way to approach ascending aortic atheromatous disease, many are not, which is clearly the case regarding one’s genetic composition. Several recent trials have highlighted how our genetic milieu either increases the predisposition for neurologic injury or impairs the ability to recover once that injury has occurred. Despite pointing to identifiable yet sometimes divergent genetic risk factors, each of these studies has distinct strengths and weaknesses. However, regardless of reports of significant findings that provide provocative scientific insights, the study and understanding of perioperative genomics is in its relative infancy. Indeed, there are several thematic deficiencies present in most of the reported studies. The first and foremost shortcoming relates to the relatively small size of most trials. Although some of the trials are larger than the majority of other perioperative clinical trials, they are smaller than needed to avoid the problems of poor statistical power, multiple comparisons, and the seemingly ever-changing bioinformatics field. However, advancements in analytical techniques with expanded capability and accuracy have facilitated gathering the needed genetic information in a more cost-effective manner, making it possible to study larger populations. The incredible complexity of our genetic code presents an expanding challenge to our ability to fully understand the effects of genetic variation. Variations in genetic make-up have been described by the concept of single nucleotide polymorphisms (SNPs), where individual nucleotides (i.e., base pairs) differ within specific genes, thus producing various alleles. The limitations of analytical techniques have restricted the number of SNPs that can reasonably be interrogated. It has also led us to examine specific and pre-determined, though biologically plausible, targets. However, these a priori defined SNPs may completely miss the more important and as yet unknown variants. As a result, whole-genotype analysis, although suffering its own set of limitations, has improved the H. P. Grocott, MD (&) Departments of Anesthesia and Surgery, University of Manitoba, CR3008-369 Tache Avenue, Winnipeg, MB R2H 2A6, Canada e-mail: hgrocott@sbgh.mb.ca

Management of Neurologic Complications of Thoracic Aortic Surgery

Neurologic complications of thoracic aortic surgery are strongly associated with increased morbidity and mortality. Identifying preoperative risk factors for neurologic injury may enable us to refine our perioperative approach, and to lessen or avoid these complications. Methods to identify stroke and spinal ischemia intraoperatively such as neurophysiologic monitoring may enable us to improve outcomes in these patients by immediately instituting measures to improve brain and spine perfusion. The development of both protocols and therapies to treat these complications has allowed us to mitigate and, at times, reverse neurologic injury both intraoperatively and postoperatively.

Embolic material generated by multiple aortic crossclamping: a perfusion model with human cadaveric aorta

Background: Atherosclerosis of the ascending aorta and use of aortic crossclamping are risk factors for neurologic injury during cardiac surgery. Objectives Repeated aortic manipulation is part of the surgical approach to most cardiac operations. The aim of this study was to assess the amount and size of particulate matter that is dislodged from the aortic wall as a function of repeated aortic crossclamping. Methods In 10 subjects undergoing autopsy the aorta was dissected and mounted in a perfusion model. The ascending aorta was crossclamped and washed out 10 times, with the perfusate collected in aliquots (1 to 10). The aliquots were examined by computerized image processing, both macroscopically and under the microscope for calcified and cellular material. Results Aortic crossclamping produced substantial output of particulate matter. After repeated aortic crossclamping the number of particles decreased ( P = .012) and approached the baseline for aliquots 6 to 10. The average particle diameter was 0.63 ± 0.03 mm, with a maximum of 4.74 mm. Similar variability in particle outputs were recorded microscopically, with findings of both calcified and cellular material. Nine of 10 aortas had calcifications seen during simple visual inspection. Conclusions The washouts of dislodge material at aortic crossclamping had embolic potential. During the initial aortic crossclamping procedures the amount of particles was substantial, both macroscopically and microscopically. On the microscopic scale noncalcified cellular debris represents a significant pool of embolic material. Repeated aortic crossclamping reduced the amount of particles. These findings question surgical techniques associated with repeated aortic crossclamping.

Treatment planning in severe scoliosis: the role of MRI.

The use of magnetic resonance imaging (MRI) in the preoperative investigation of children with idiopathic scoliosis is controversial. Syringomyelia and other intraspinal lesions may be risk factors for neurological injury during surgical correction. Our purpose was to investigate whether pathology of the neuraxis is associated with scoliosis and to detect lesions which may threaten neurological sequelae during distraction and instrumented correction. We obtained T1- and T2-weighted images of 40 children (28 girls, 12 boys), mean age 12.7 years with severe idiopathic scoliosis (Cobb angle 50-70 degrees) obtained in coronal, sagittal and axial planes from the posterior cranial fossa to the sacrum, and these were assessed by two neuroradiologists and an orthopaedic surgeon prior to further treatment planning. Abnormalities of the neuraxis were found in 24 patients (60%); five (12%) had two or more lesions. No abnormalities of the neuraxis were found in 16 patients (40%). There were 15 patients (38%) with intraspinal abnormalities who deteriorated clinically and nine (22%) who showed no clinical changes. We transferred 16 patients (40%) from the orthopaedic to the neurosurgical department for further assessment. Our results suggest that one should investigate the neuraxis with MRI before contemplating orthopaedic surgical correction of severe idiopathic scoliosis, because the findings may lead to a change of procedure.

Neurologic outcome after ascending aorta–aortic arch operations: Effect of brain protection technique in high-risk patients

Objective: We sought to assess the optimal strategy for avoiding neurologic injury after aortic operations requiring hypothermic circulatory arrest. Methods: All 717 patients who survived ascending aorta–aortic arch operations through a median sternotomy since 1986 were examined for factors influencing stroke. Temporary neurologic dysfunction was assessed in all patients who survived the operation without stroke since 1993. Multivariate analyses were carried out to determine independent risk factors for neurologic injury. Results: Independent risk factors for stroke were as follows: age greater than 60 years (P <.001; odds ratio, 4.5); emergency operation (P =.02; odds ratio, 2.2); new preoperative neurologic symptoms (P =.05; odds ratio, 2.9); presence of clot or atheroma (P <.001; odds ratio, 4.4); mitral valve replacement or other concomitant procedures (P =.055; odds ratio, = 3.7); and total cerebral protection time, defined as the sum of hypothermic circulatory arrest and any retrograde or antegrade cerebral perfusion (P =.001; odds ratio, 1.02/min). In 453 patients surviving operations without stroke after 1993, independent risk factors for temporary neurologic dysfunction included age (P <.001; odds ratio, 1.06/y), dissection (P =.001; odds ratio, 2.2), need for coronary artery bypass grafting (P =.006; odds ratio, 2.1) or other procedures (P =.023; odds ratio, 3.4), and total cerebral protection time (P <.001; odds ratio, 1.02/min). When all patients with total cerebral protection times between 40 and 80 minutes were examined, the method of cerebral protection did not influence the occurrence of stroke, but antegrade cerebral perfusion resulted in a significant reduction in incidence on temporary neurologic dysfunction (P =.05; odds ratio, 0.3). Conclusions: The occurrence of stroke is principally determined by patient- and disease-related factors, but use of antegrade cerebral perfusion can significantly reduce the occurrence of temporary neurologic dysfunction. (J Thorac Cardiovasc Surg 2001;121:1107-21)

Neurologic Injury in Cardiac Surgery: Aortic Atherosclerosis Emerges as the Single most Important Risk Factor

With older and sicker patients undergoing cardiac surgery, neurologic injury has emerged as an increasingly important cause of rising costs, morbidity and mortality. Several studies investigating the relationship between atherosclerotic aortic disease and subsequent adverse clinical outcomes have demonstrated that the single most important risk factor for neurologic injury following cardiac surgery is the presence of aortic atheromatous disease. The results of these studies suggest that atheroemboli are correlated with neurologic injury following cardiac surgery. Surgical techniques to avoid and prevent particulate debris during cardiac surgery may be a major step in preventing severe neurologic injury.

Reduction of neurologic injury after high-risk thoracoabdominal aortic operation

Background. Of all aortic operations, thoracoabdominal aortic repairs have the highest risk of spinal cord neurologic injury, manifest by lower limb paraplegia or paraparesis. Cerebrospinal fluid drainage combined with intrathecal papaverine (CSFDr + IP) may reduce the risk and severity of neurologic injury. The objective of this study was to evaluate the effect of CSFDr + IP to prevent neurologic injury after high-risk thoracoabdominal aneurysm repairs. Methods. We screened 64 patients before operation with descending thoracic or thoracoabdominal aneurysms for possible inclusion in a prospective, randomized study. Thirty-three patients with high-risk type I and II thoracoabdominal aneurysms met inclusion criteria and 17 were randomly assigned to CSFDr + IP and 16 to the control group. The study was terminated early after interim analysis revealed a significant difference. Results. Of 64 patients screened, 2 patients died after operation (3.1%, 2/64); both were in the randomized study (6%, 2/33), and neither had a neurologic injury. Neurologic injury developed in 2 CSFDr + IP patients and 7 control patients ( p = 0.0392). Control patients also had lower postoperative motor strength scores ( p = 0.0340). On multivariate analysis, risk factors for neurologic injury included ( p < 0.05) longer cross-clamp time, failure to actively cool with bypass, and postoperative hypotension, whereas CSFDr + IP was protective. Logistic regression showed that CSFDr + IP and active cooling significantly reduced the risk of injury and that the two combined modalities were additive. Of 64 patients screened, only 2 (3%) had a permanent neurologic deficit preventing ambulation. Conclusions. For high-risk thoracoabdominal aneurysms, CSFDr + IP was effective in reducing the incidence and severity of neurologic injury. Active cooling may be further additive to CSFDr + IP protection, although this needs to be confirmed in a larger study.

Cerebrovascular Assessment of the High-Risk Patient

With increased attention to the causes and effects of neurologic injury related to cardiopulmonary bypass anesthesia and surgery, multiple modality examination and monitoring of cerebral function and perfusion in the perioperative period may prove to be advantageous. Transcranial Doppler examination and monitoring is inexpensive, noninvasive, safe, provides unique information about the functional status of the intracranial circulation, and complements the duplex Doppler study of the extracranial carotid vessels of the neck for preoperative evaluation of the surgical patient. The transcranial Doppler examination permits quantitation of blood flow velocity of the intracranial vessels, evaluation of autoregulatory capacity and vasomotor reserve, determination of symmetry of flow velocity in the circle of Willis, assessment of collateral circulatory capacity, examination of vessels not accessible to the duplex Doppler and serves as a baseline for intraoperative monitoring and the postoperative examination. Noninvasive, unilateral or bilateral, continuous monitoring of brain blood flow velocity intraoperatively or postoperatively with trending, storage, and correlation with other physiologic variables provides evidence of cerebral perfusion, occurrence and rate of cerebral embolism, and continuous monitoring of therapeutic interventions. A review of the incidence of stroke and neuropsychologic deficit after bypass surgery is focused on parameters amenable to diagnosis using transcranial Doppler. Patient-specific risk factors for neurologic injury derived from previous studies are discussed as well as risk factors that are related to anesthetic and surgical management and equipment. A description of Doppler technology and the correlation of transcranial Doppler findings with angiography and radionucleotide scans establishes the accuracy of the Doppler examination. The preoperative examination, provocative tests of vasomotor reserve, the evaluation of cerebral collateral circulation, and examples of Doppler applications are discussed.

Long-term effects of neonatal ischemic-hypoxic brain injury on sensorimotor and locomotor tasks in rats

Perinatal ischemia and/or hypoxia in humans are major risk factors for neurologic injury that often manifest as sensorimotor and locomotor deficits throughout development and into maturity. In these studies, we utilized an established model of neonatal ischemic-hypoxia that creates unilateral striatal, cortical, and hippocampal damage (Rice III, J.E., Vanucci, R.C. and Brierley, J.B., Ann. Neurol., 9 (1981) 131–141)) to investigate sensorimotor and locomotor deficits in these animals during development and as adults. Sensorimotor deficits were examined by measuring the amount of time that the animals were able to remain on a rotating treadmill. Locomotor abnormalities were assessed by measuring apomorphine-induced rotational asymmetry. Following the neonatal ischemic-hypoxic episode, at 3–9 weeks of age, animals were not able to remain on the treadmill as long as their normal littermate controls. In addition, these animals demonstrated an abnormal, ipsiversive rotational asymmetry in response to systemic administration of apomorphine. When these animals reached adulthood, the degree of atrophy in specific regions of the damaged hemisphere was quantified using measurements of cross-sectional area. The mean cross-sectional area of the striatum was decreased by 29%, the sensorimotor cortex area by 26%, and the dorsal hippocampus cross-sectional area was approximately 6% of its normal size. These data suggest that this rodent model of neonatal ischemic-hypoxic brain injury results in cerebral atrophy and long-lasting sensorimotor and locomotor deficits. These particular behavioral tasks may be used in future studies to assess locomotor and sensorimotor deficits following neonatal ischemic-hypoxic brain injury.

Cerebrovascular assessment of the high-risk patient: The role of transcranial doppler ultrasound

With increased attention to the causes and effects of neurologic injury related to cardiopulmonary bypass anesthesia and surgery, multiple modality examination and monitoring of cerebral function and perfusion in the perioperative period may prove to be advantageous. Transcranial Doppler examination and monitoring is inexpensive, noninvasive, safe, provides unique information about the functional status of the intracranial circulation, and complements the duplex Doppler study of the extracranial carotid vessels of the neck for preoperative evaluation of the surgical patient. The transcranial Doppler examination permits quantitation of blood flow velocity of the intracranial vessels, evaluation of autoregulatory capacity and vasomotor reserve, determination of symmetry of flow velocity in the circle of Willis, assessment of collateral circulatory capacity, examination of vessels not accessible to the duplex Doppler and serves as a baseline for intraoperative monitoring and the postoperative examination. Noninvasive, unilateral or bilateral, continuous monitoring of brain blood flow velocity intraoperatively or postoperatively with trending, storage, and correlation with other physiologic variables provides evidence of cerebral perfusion, occurrence and rate of cerebral embolism, and continuous monitoring of therapeutic interventions. A review of the incidence of stroke and neuropsychologic deficit after bypass surgery is focused on parameters amenable to diagnosis using transcranial Doppler. Patient-specific risk factors for neurologic injury derived from previous studies are discussed as well as risk factors that are related to anesthetic and surgical management and equipment. A description of Doppler technology and the correlation of transcranial Doppler findings with angiography and radionucleotide scans establishes the accuracy of the Doppler examination. The preoperative examination, provocative tests of vasomotor reserve, the evaluation of cerebral collateral circulation, and examples of Doppler applications are discussed.

Syringomyelia

An 18-year-old patient with "idiopathic" adolescent scoliosis is presented. A thoracic syrinx was detected as an incidental finding during magnetic resonance imaging of the spine. Syringomyelia may be a risk factor for neurologic injury during correction of scoliosis, and in these cases, spinal cord monitoring may be of particular value. Spinal distraction and instrumentation carry a risk of neurologic damage in patients with scoliosis and associated syringomyelia. Syringomyelia is a cause of scoliosis, and although neurologic problems are the usual symptom, scoliosis may be the only sign at initial examination. A higher risk of neurologic injury has been reported in corrective surgical treatment of patients with syringomyelia. The mechanism of cord damage is unclear. Monitoring of spinal cord function is recommended to detect intraoperative neurological injury, which may be reversed on removing distraction and implants. Intraoperative somatosensory-evoked potential (SSEP) spinal cord monitoring detected possible cord damage during outrigger distraction. Reduction of distraction led to a recovery of SSEPs and a satisfactory operative outcome. Syringomyelia may be a risk factor for neurologic injury during correction of scoliosis, and SSEP spinal cord monitoring may identify and prevent intraoperative spinal cord injury.

Thoracoabdominal aortic aneurysms with special reference to technical problems and complications

Background. Of all aortic operations, thoracoabdominal aortic repairs have the highest risk of spinal cord neurologic injury, manifest by lower limb paraplegia or paraparesis. Cerebrospinal fluid drainage combined with intrathecal papaverine (CSFDr + IP) may reduce the risk and severity of neurologic injury. The objective of this study was to evaluate the effect of CSFDr + IP to prevent neurologic injury after high-risk thoracoabdominal aneurysm repairs.Methods. We screened 64 patients before operation with descending thoracic or thoracoabdominal aneurysms for possible inclusion in a prospective, randomized study. Thirty-three patients with high-risk type I and II thoracoabdominal aneurysms met inclusion criteria and 17 were randomly assigned to CSFDr + IP and 16 to the control group. The study was terminated early after interim analysis revealed a significant difference.Results. Of 64 patients screened, 2 patients died after operation (3.1%, 2/64); both were in the randomized study (6%, 2/33), and neither had a neurologic injury. Neurologic injury developed in 2 CSFDr + IP patients and 7 control patients (p = 0.0392). Control patients also had lower postoperative motor strength scores (p = 0.0340). On multivariate analysis, risk factors for neurologic injury included (p < 0.05) longer cross-clamp time, failure to actively cool with bypass, and postoperative hypotension, whereas CSFDr + IP was protective. Logistic regression showed that CSFDr + IP and active cooling significantly reduced the risk of injury and that the two combined modalities were additive. Of 64 patients screened, only 2 (3%) had a permanent neurologic deficit preventing ambulation.Conclusions. For high-risk thoracoabdominal aneurysms, CSFDr + IP was effective in reducing the incidence and severity of neurologic injury. Active cooling may be further additive to CSFDr + IP protection, although this needs to be confirmed in a larger study.

Hypothermic circulatory arrest as a surgical adjunct: A 5-year experience with 60 adult patients

As a surgical adjunct, the technique of hypothermic circulatory arrest (HCA) is well established in pediatric cardiac surgery but is used less frequently in adults. This study was undertaken to review the application, utility, and safety of HCA in adult surgery at a single institution. Between January 1985 and October 1990, 60 adult patients (>18 years old) underwent surgical procedures that included HCA. There were 30 men and 30 women; mean patient age was 56.4 years (range, 20 to 81 years). Operative procedures were thoracic aortic aneurysm repair (35 patients, 58%), resection of intraabdominal malignancy (15 patients, 25%), coronary artery bypass (4 patients, 7%), and other miscellaneous procedures (6 patients, 10%). Eighty-two percent of the procedures were elective, whereas 18% were emergencies. Mean circulatory arrest time was 28.5 minutes (range, 2 to 64 minutes). Operative mortality was 15%; by multivariate analysis, risk factors for death included prolonged cardiopulmonary bypass time ( p < 0.05), higher post-HCA rectal temperature ( p < 0.05), and intraoperative hypotension ( p < 0.001). Patient age, sex, emergency status, duration of HCA, and perfusion variables on cardiopulmonary bypass did not predict operative mortality. The incidence of perioperative neurologic injury was 15%. The only risk factor for neurologic injury was intraoperative hypotension ( p < 0.05). One- and 3-year actuarial survival for patients undergoing operation on the heart or great vessels was 75.9% and 70%, respectively, whtreas patients with intraabdominal malignancy had 75% and 23.4% 1- and 3-year survival. This review suggests that HCA can play an important supportive role in the management of selected complex surgical problems, but its safe practice depends on achieving deep hypothermia and maintaining stable perioperative hemodynamics.