Martha M. Wynn

Complications of spinal fluid drainage in thoracoabdominal aortic aneurysm repair: A report of 486 patients treated from 1987 to 2008

OBJECTIVE Spinal fluid drainage reduces paraplegia risk in thoracic (TAA) and thoracoabdominal (TAAA) aortic aneurysm repair. There has not been a comprehensive study of the risks of spinal fluid drainage and how these risks can be reduced. Here we report complications of spinal fluid drainage in patients undergoing TAA/TAAA repair. METHODS The study comprised 648 patients who had TAA or TAAA repair from 1987 to 2008. Spinal drains were used in 486 patients. Spinal fluid pressure was measured continuously, except when draining fluid, and was reduced to <6 mm Hg during thoracic aortic occlusion and reperfusion. After surgery, spinal fluid pressure was kept <10 mm Hg until patients were awake with normal leg lift. Drains were removed 48 hours after surgery. Spinal and head computed tomography (CT) scans were performed in patients with bloody spinal fluid or neurologic deficit. We studied the incidence of headache treated with epidural blood patch, infection, bloody spinal fluid, intracranial and spinal bleeding on CT, as well as the clinical consequences. RESULTS Twenty-four patients (5%) had bloody spinal fluid. CT exams showed seven had no evidence of intracranial hemorrhage, 14 (2.9%) had intracranial blood without neurologic deficit, and three with intracranial bleeding and cerebral atrophy had neurologic deficits (1 died, 1 had permanent hemiparesis, and 1 with transient ataxia recovered fully). Two patients without bloody spinal fluid or neurologic deficit after surgery presented with neurologic deficits 5 days postoperatively and died from acute on chronic subdural hematoma. Neurologic deficits occurred after spinal fluid drainage in 5 of 482 patients (1%), and 3 died. The mortality from spinal fluid drainage complications was 0.6% (3 of 482). By univariate and multivariate analysis, larger volume of spinal fluid drainage (mean, 178 mL vs 124 mL, P < .0001) and higher central venous pressure before thoracic aortic occlusion (mean, 16 mm Hg vs 13 mm Hg, P < .0012) correlated with bloody spinal fluid. CONCLUSION Strategies that reduce the volume of spinal fluid drainage but still control spinal fluid pressure are helpful in reducing serious complications. Patients with cerebral atrophy are at increased risk for complications of spinal fluid drainage.

Cardiac function is a risk factor for paralysis in thoracoabdominal aortic replacement

PURPOSE We studied factors that influence paralysis risk, renal function, and mortality in thoracoabdominal aortic replacement. METHODS We prospectively collected preoperative demographic and intraoperative physiologic data and used univariate and multivariate analyses to correlate this data with risk factors for paralysis. A mathematical model of paraplegia risk was used to study the efficacy of paraplegia reduction strategies. We analyzed preoperative and operative factors for paralysis risk, renal function, and mortality for 217 consecutive patients surgically treated from 1984 through 1996 for 176 thoracoabdominal and 41 thoracic aneurysms at the University of Wisconsin Hospital and Clinics. No patient had intercostal reimplantation or assisted circulation. One hundred fifty patients (group A) received cerebrospinal fluid drainage (CSFD) and low-dose naloxone (1 microg/kg/hour) as adjuncts to reduce the risk of paralysis. Sixty-seven patients (group B) did not receive CSFD and naloxone. RESULTS Seventeen deficits occurred in 205 surviving patients: 5 of the 147 in group A (expected deficits = 31) and 12 of the 58 in group B (expected deficits = 13) (p < 0.001). In a multivariate logistic regression model, acute presentation, Crawford type 2 aneurysm, group B membership, and a decrease in cardiac index with aortic occlusion remained significant risk factors for deficit (p < 0.0001). By odds ratio analysis, group A patients had 1/40th the risk of paralysis of group B. The only significant predictor of postoperative renal function was the preoperative creatinine level (p < 0.0001); renal revascularization significantly improved renal function. The mortality rate was 1.6% (2) for patients undergoing elective treatment and 21% (19) for patients who had acute presentations. Acute presentation, age, and the preoperative creatinine level were found to be significant factors for operative mortality in a logistic regression model (p < 0.001) and defined a group at high risk for death. CONCLUSIONS CSFD and low-dose naloxone significantly reduce the paralysis risk associated with thoracoabdominal aortic replacement. A decrease in the cardiac index with aortic occlusion is a previously unreported variable that defines a subset of patients at higher risk for paralysis.

A quantitative assessment of the impact of intercostal artery reimplantation on paralysis risk in thoracoabdominal aortic aneurysm repair.

Objectives:We previously demonstrated an 80% reduction in paraplegia risk using hypothermia, naloxone, steroids, spinal fluid drainage, intercostal ligation, and optimizing hemodynamic parameters. This report demonstrates that intercostal revascularization for the last 3 years further reduced our paraplegia risk index by 75%. Methods:We evaluated 655 patients who had thoracic or thoracoabdominal aneurysm repair for factors that affected paraplegia risk including aneurysm extent, acuity, cardiac function, blood pressure mean arterial pressure, and spinal fluid drainage with naloxone (SFDN). Eighteen patients died during or shortly after surgery leaving 637 patients for analysis of paralysis. We evaluated the effect of intercostal reimplantation (IRP) using a highly accurate (r2 > 0.88) paraplegia risk index we developed and published previously. Results:Fifty-eight percent of patients were male with a mean age of 67. Thirty-three percent were acute with rupture, acute dissection, mycotic aortitis, and trauma. Eighty (12%) had dissections. Thirty-five patients had paraplegia or paraparesis (5.4%). Significant factors by univariate analysis (P < 0.05) were Crawford type 2, acuity, SFDN, cardiac index after unclamping, mean arterial pressure during crossclamping, and IRP. In multivariate modeling, aneurysm extent, SFDN, acuity, and IRP remained significant (P < 0.02). The paraplegia risk index declined from 0.20 to 0.05 (P < 0.03). Conclusions:The incidence of paralysis after TAAA repair decreased from 4.83% to 0.88% and paralysis risk index decreased from 0.26 to 0.05 when intercostal artery reimplantation was added to neuroprotective strategies that had already substantially reduced paralysis risk. These findings suggest that factors that affect collateral blood flow and metabolism account for approximately 80% of paraplegia risk and intercostal blood flow accounts for 20% of risk. This suggests a limit to paraplegia risk reduction in thoracoabdominal endograft patients. Early results in this emerging field support this prediction of high paraplegia risk with thoracoabdominal branched endografts with extensive aortic coverage.

A modern theory of paraplegia in the treatment of aneurysms of the thoracoabdominal aorta: An analysis of technique specific observed/expected ratios for paralysis.

OBJECTIVE To demonstrate that a modern theory of paraplegia prevention in thoracoabdominal aortic (TAAA) surgery is primarily non-anatomic and derives from experimentally validated interventions that prolong the ischemic tolerance, reduce reperfusion injury, and enhance the collateral perfusion of the spinal cord with or without assisted circulation. METHODS Using an accurate predictive model (r(2) > 0.95) for paraplegia risk we studied the effects of protective strategies in 82 clinical series reporting more than 15,000 patients treated from 1985 to 2008. The observed/expected (O/E) ratios were calculated for each series and the results were grouped by technique. The effect of interventions such as spinal fluid drainage (SFD), systemic hypothermia, epidural cooling, and naloxone on O/E ratios were studied. We analyzed changes in O/E ratios from Era 1 (1985 to 1997) to Era 2 (1997 to 2008) and within treatment techniques over time. RESULTS The mean O/E ratio for paraplegia for all patients declined from 1.13 in Era 1 to 0.26 in Era 2. Adding SFD to patients treated with assisted circulation (AC) decreased the O/E ratio from 1.03 to 0.24 (P < .0001). Adding SFD to patients treated with aortic clamping without AC (XCL) decreased O/E from 0.91 to 0.23 (P = .0013). O/E for hypothermic arrest (HA) declined from 0.42 to 0.14 with SFD. The addition of SFD to AC, XCL, and HA accounted for most of the decline in O/E between Eras. Other factors which played a less defined but important role in the decline in O/E ratios were attention to higher mean arterial pressures (MAPs), more hypothermia, and neurochemical protection. CONCLUSION Paraplegia causation is anatomic but paraplegia prevention is physiologic (non-anatomic). We demonstrate that by using hypothermia, SFD, and increasing MAP, clinicians had similar improvements in paraplegia, reducing O/E deficit ratios from 1.03 to as low as 0.16, with or without intercostal reimplantation, and whether or not assisted circulation was used. Understanding the fundamental principles of paraplegia prevention and how to apply protective strategies leads to a reduction in paralysis in clinical series with or without the use of assisted circulation. This modern theory of paraplegia has significant implications for the rapidly advancing field of TAAA repair with branched endografts where the same principles apply.

Outcomes in open repair of the thoracic and thoracoabdominal aorta

There has been a significant decrease in mortality and paraplegia risk during the last 25 years in the treatment of thoracic and thoracoabdominal aortic disease (Fig 1). The primary factors in this improvement have been the use of cerebrospinal fluid drainage and moderate to profound hypothermia, combined with optimizing arterial perfusion pressure and cardiac function and the use of neurochemical protection. Effective application of these critical concepts has resulted in a 75% to 80% reduction in paraplegia and a 50% reduction in mortality in most single-center reports where surgery is supported by a dedicated anesthesia and surgical team using treatment protocols that optimize these critical factors. However, there is still considerable variation in mortality and paraplegia rates in clinical reports, with little understanding of the causes of this variation in outcomes (Table I). This report will attempt to explain this variation and identify some of the factors associated with mortality, paraplegia, renal failure, and long-term functional outcome. To accomplish this, a paraplegia risk model based on the extent of aortic replacement (Crawford classification) and clinical presentation (acute and dissection), and a mortality risk model to compare risk from published reports are used to analyze results from clinical reports. The mortality risk model is based on the proportion of acute patients and the predicted number of paraplegias multiplied by a risk coefficient of 0.3 (the coefficient with the highest R value and approximates the mean acute and paraplegia associated mortality). This mortality model accounts for 76% of the variation between reports (Fig 2). The data for this analysis come from our own prospectively maintained database, which now includes 771 patients, and a database of approximately 100 publications

Matrix Metalloproteinase-9 Genotype as a Potential Genetic Marker for Abdominal Aortic Aneurysm

Background—Degradation of extracellular matrix support in the large abdominal arteries contribute to abnormal dilation of aorta, leading to abdominal aortic aneurysms, and matrix metalloproteinase-9 (MMP-9) is the predominant enzyme targeting elastin and collagen present in the walls of the abdominal aorta. Previous studies have suggested a potential association between MMP-9 genotype and abdominal aortic aneurysm, but these studies have been limited only to the p-1562 and (CA) dinucleotide repeat microsatellite polymorphisms in the promoter region of the MMP-9 gene. We determined the functional alterations caused by 15 MMP-9 single-nucleotide polymorphisms (SNPs) reported to be relatively abundant in the human genome through Western blots, gelatinase, and promoter–reporter assays and incorporated this information to perform a logistic-regression analysis of MMP-9 SNPs in 336 human abdominal aortic aneurysm cases and controls. Methods and Results—Significant functional alterations were observed for 6 exon SNPs and 4 promoter SNPs. Genotype analysis of frequency-matched (age, sex, history of hypertension, hypercholesterolemia, and smoking) cases and controls revealed significant genetic heterogeneity exceeding 20% observed for 6 SNPs in our population of mostly white subjects from Northern Wisconsin. A step-wise logistic-regression analysis with 6 functional SNPs, where weakly contributing confounds were eliminated using Akaike information criteria, gave a final 2 SNP (D165N and p-2502) model with an overall odds ratio of 2.45 (95% confidence interval, 1.06–5.70). Conclusions—The combined approach of direct experimental confirmation of the functional alterations of MMP-9 SNPs and logistic-regression analysis revealed significant association between MMP-9 genotype and abdominal aortic aneurysm.

Complications of spinal fluid drainage in thoracic and thoracoabdominal aortic aneurysm surgery in 724 patients treated from 1987 to 2013.

OBJECTIVE To study complications from spinal fluid drainage in open thoracic/thoracoabdominal and thoracic endovascular aortic aneurysm repairs to define risks of spinal fluid drainage. DESIGN Retrospective, prospectively maintained, institutionally approved database. SETTING Single institution university center. PARTICIPANTS 724 patients treated from 1987 to 2013 INTERVENTIONS: The authors drained spinal fluid to a pressure≤6 mmHg during thoracic aortic occlusion/reperfusion in open and ≤8 mmHg after stent deployment in endovascular procedures. Low pressure was maintained until leg strength was documented. If bloody fluid appeared, drainage was stopped. Head computed tomography (CT) and, if indicated, spine CT and magnetic resonance imaging (MRI) were performed for bloody spinal fluid or neurologic deficit. MEASUREMENTS AND MAIN RESULTS Spinal fluid drainage was studied for bloody fluid, CT/MRI-identified intracranial and spinal bleeding, neurologic deficit, and death. Seventy-three patients (10.1%) had bloody fluid; 38 (5.2%) had intracranial blood on CT. One patient had spinal epidural hematoma. Higher volume of fluid drained and higher central venous pressure during proximal clamping were associated with intracranial blood. Most patients with intracranial blood were asymptomatic. Six patients had neurologic deficits: of the 6, 3 died (0.4%), 1 (0.1%) had permanent hemiparesis, and 2 recovered. Three of the six deficits were delayed, associated with heparin anticoagulation. CONCLUSIONS 10% of patients had bloody spinal fluid; half of these had intracranial bleeding, which was almost always asymptomatic. In these patients, immediately stopping drainage and correcting coagulopathy may decrease the risk of serious complications. Neurologic deficit from spinal fluid drainage is uncommon (0.8%), but has high morbidity and mortality.

Technique of Thoracoabdominal Aneurysm Repair

Surgical repair of thoracoabdominal aneurysms (TAA) is a formidable task because of the scope of the procedure and the physiologic consequences of interrupting the blood supply to major organs and segmental spinal arteries. In the early days of repair of these aneurysms, mortality rates as high as 30% were reported. The addition of renal failure and paraplegia associated with repair pushed combined morbidity and mortality rates still higher.’ Dr. Stanley Crawford2 of Baylor University in Houston, Texas, reported his first personal series in 1974. He demonstrated that simplifying the surgical technique by use of graft inclusion and simple aortic cross-clamping without assisted circulation could lower the elective mortality rate to the 10% range and reduce overall significant morbidity rates to 25% with a 15% incidence of paraplegia or paraparesis. His vast experience and results set the standard for r e ~ a i r . ~ Dr. Crawford categorized patients by length of aortic replacement (Crawford types I to IV) and demonstrated that the risks of paraplegia and death were related to the amount of aorta being replaced and the clinical presentation (elective, ruptured, acute, or chronic dissection). He reimplanted intercostal arteries but was unable to demonstrate that reimplantation reduced the incidence of paraplegia, and the paraplegia rate remained constant during his career. He also demonstrated that assisted circulation during repair did not alter the paraplegia risk.4 The risk factors for paraplegia as defined by Dr. Crawford remain constant, and we were able to quantitatively model paraplegia risk.’ These efforts show that 95% or more of the

A New Intercostal Artery Management Strategy for Thoracoabdominal Aortic Aneurysm Repair

OBJECTIVE The purpose of this study is to describe a new approach for addressing the intraoperative management of intercostal arteries during thoracoabdominal aortic aneurysm (TAAA) repair, using preoperative spinal MRA for detection of intercostal arteries supplying the anterior spinal artery. METHODS Patients undergoing TAAA repair from August 2005 to September 2007 were included. Spinal artery MRA was performed to identify the anterior spinal artery, the artery of Adamkiewicz, and its major intercostal source artery (SA-AAK). Intraoperative spinal cord protection was carried out using standard techniques. Important intercostal arteries were either preserved or reimplanted as a button patch after removing aortic clamps. Demographic and perioperative data were collected for review. Analysis was performed with Fishers exact test or Students t-test, where applicable, using SAS ver. 8.0 (Cary, NC). RESULTS Spinal artery MRA was performed in 27 patients. The SA-AAK was identified in 85% of preoperative studies. Open or endovascular repair was performed in 74% and 26% of patients, respectively. The SA-AAK was preserved or reimplanted in 13 (65%) of patients who underwent open repair. A mean of 1.67 (range 1-3) intercostal arteries were reimplanted. All patients undergoing endovascular repair necessitated coverage of the SA-AAK. No patient developed immediate or delayed paraplegia. Longer mean operative times in the reimplanted cohort were not statistically significant (330 versus 245 min, P = 0.1). CONCLUSION The SA-AAK identified by MRA can be preserved or safely reimplanted after TAAA repair. Further study is warranted to determine if selective intercostal reimplantation can reduce the risk of immediate or delayed paraplegia.

Multifactoral Nature of Spinal Cord Circulation

Since 1988, our paraplegia risk has been one-tenth the risk of the standard Crawford technique with or without assisted circulation. This significant reduction in paraplegia risk was accomplished with a factoral problem-solving approach that demonstrated the additive effects of early intercostal artery ligation, moderate surface cooling, cerebral spinal fluid drainage, and endorphin receptor blockade (naloxone) as the primary factors involved.