John R. Hoch

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.

Monocyte Chemotactic Protein-1 Expression Is Associated With the Development of Vein Graft Intimal Hyperplasia

Infiltration of immunologically active cells into vein grafts is concomitant with the development of intimal hyperplasia (IH) and often leads to obliterative stenosis and graft failure. Previous work has demonstrated the prolonged presence of monocytes and macrophages in vein grafts. The stimuli attracting these macrophages remain unidentified. Monocyte chemotactic protein-1 (MCP-1), a potent and specific chemokine for monocytes/macrophages, is secreted by smooth muscle cells, endothelial cells, fibroblasts, and leukocytes, all of which are present in grafted veins. In this study, we examined the temporal profile of MCP-1 gene expression in rat vein grafts by using reverse transcription-polymerase chain reaction (PCR) and immunohistochemistry. Epigastric vein-to-femoral artery bypass grafts were microsurgically placed and harvested at various time points after grafting. Histological analysis confirmed the consistent development of IH. PCR was performed and relative levels of MCP-1 quantified by autoradiography. Our results show that MCP-1 mRNA levels increased 28-fold by 4 hours after grafting and up to 117-fold by 1 week. After this time MCP-1 mRNA levels decreased; nonetheless, even at 8 weeks after grafting, message levels remained elevated 7-fold above baseline. Immunoreactive MCP-1 protein and ED1+ macrophages were detected at all time points; the degree of immunostaining correlated with MCP-1 mRNA levels. Our results support the hypothesis that upregulation of MCP-1 gene expression in vein grafts results in the recruitment of monocytes and tissue macrophages to the vein wall, which leads to IH. The correlation between monocyte/ macrophage infiltration and IH suggests a critical role for these cells in IH development.

Combined use of duplex imaging and magnetic resonance angiography for evaluation of patients with symptomatic ipsilateral high-grade carotid stenosis.

PURPOSE Advances in cerebral vascular imaging suggest that patients with critical levels of carotid artery stenosis (> 70%) who have symptoms can be identified accurately and necessary information about the intracranial and extracranial circulation obtained before surgery without conventional angiography. We have used carotid duplex imaging in combination with magnetic resonance angiography (MRA) to evaluate 20 patients with symptomatic ipsilateral high-grade carotid stenosis. METHODS All patients underwent CT and magnetic resonance imaging brain scans, as well as MRA and conventional arteriography of the cerebral circulation. Magnetic resonance angiograms were obtained with two-dimensional phase contrast and time-of-flight techniques. Phase contrast was used for intracranial vascular imaging and for determining qualitative flow velocities and the direction of blood flow in the circle of Willis. Two-dimensional time of flight was used to assess the carotid bifurcations. RESULTS Twenty patients with symptoms (six with strokes, 11 with transient ischemic attacks, and three with amaurosis fugax) had duplex evidence of high-grade carotid stenoses. Computed tomographic and magnetic resonance brain scans were positive for cerebral infarction in six patients with clinical strokes. Comparison of MRA with conventional angiography was 91% accurate for high-grade stenoses and occlusions (sensitivity 100% and specificity 90% for stenosis; sensitivity/specificity was 100% for complete occlusion). Comparison of duplex imaging with conventional angiography demonstrated 86% accuracy for detection of severe stenosis or occlusion (sensitivity 94% and specificity 89% for stenosis; sensitivity and specificity were 100% for complete occlusion). CONCLUSIONS This study suggests that combined use of MRA and duplex imaging is accurate for detection and evaluation of high-grade carotid stenoses in patients with symptoms.

Macrophage depletion alters vein graft intimal hyperplasia.

BACKGROUND The principal cause of vein graft failure is intimal hyperplasia (IH); however, its etiology remains unclear. In a rat model of vein graft IH we have observed prolonged transmural macrophage infiltration, leading us to hypothesize that these cells regulate IH. To test this, we used liposome-encapsulated dichloromethylene bisphosphonate (L-Cl2MBP) to deplete rat macrophages and observed the effects on IH. METHODS Epigastric vein-to-femoral artery grafts were microsurgically placed in male Lewis rats that had been intravenously injected with L-Cl2MBP, phosphate-buffered saline solution liposomes, or phosphate-buffered saline solution alone 2 days before surgery. Several animals in each group received a second equivalent dose at 2 weeks. Grafts, contralateral epigastric veins, spleens, and livers were harvested at 1, 2, and 4 weeks for histologic examination, immunohistochemistry, and transmission electron microscopy. RESULTS In the L-Cl2MBP-treated animals splenic and hepatic macrophages were greatly reduced, confirming the efficacy of the agent. At 1 to 2 weeks graft macrophages were significantly decreased, and there was a trend toward decreased IH. At 4 weeks macrophage numbers were normal and IH development had resumed. In contrast, the 4-week grafts treated with 2 doses of L-Cl2MBP had fewer macrophages and displayed severely attenuated IH. CONCLUSIONS The results indicate a suppression of IH as macrophages are depleted, with a resumption of the process as macrophages repopulate the graft.

Use of magnetic resonance angiography for the preoperative evaluation of patients with infrainguinal arterial occlusive disease

PURPOSE This study was designed to determine whether magnetic resonance angiography (MRA) will allow preoperative management decisions without the need for contrast arteriography in patients with lower extremity ischemia caused by infrainguinal arterial occlusive disease. METHODS Forty-five patients with lower extremity ischemia in 50 limbs were evaluated by both two-dimensional time-of-flight MRA and intraarterial digital subtraction angiography (DSA) between February 1992 and June 1995. Independent management plans were based on clinical presentation, pulse volume recordings, and separate reviews of the MRA and DSA. RESULTS Of 50 limbs, 23 required arterial bypass, 19 percutaneous transluminal angioplasty, 5 patch angioplasty, and 3 amputation. MRA and DSA correlated exactly in 89.5% of infrainguinal arterial segments, whereas interpretations disagreed in 10.5% of arterial segments. Mismatches that had an influence on patient treatment decisions occurred in only 8 (2.3%) of 352 arterial segments. Independent MRA- and DSA-based revascularization plans agreed in 45 (90%) extremities. MRA predicted the level of arterial reconstruction in all 23 limbs that required arterial bypass. MRA identified focal stenoses amenable to percutaneous transluminal angioplasty in 18 (94.7%) of the 19 limbs that ultimately underwent percutaneous transluminal angioplasty. A strategy of preoperative planning by MRA with confirmatory intraoperative arteriography would represent a 31% cost savings per patient at our institution while eliminating the morbidity of preoperative DSA. CONCLUSIONS When used in combination with the patients physical examination and segmental limb pressures with plethysmography, MRA is sufficient for planning infrainguinal arterial bypass procedures and selecting patients for percutaneous transluminal angioplasty.

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.

The temporal relationship between the development of vein graft intimal hyperplasia and growth factor gene expression

PURPOSE Intimal hyperplasia is a common cause of obstructive stenosis after arterial reconstructive procedures. It has been postulated that growth factors elaborated by vascular wall cells regulate fibroproliferative changes that can cause graft failure. This study characterizes transforming growth factor beta-1 (TGF-beta 1) and platelet-derived growth factor-A chain (PDGF-A) mRNA transcript profiles and their temporal relationship to the development of intimal hyperplasia in vein grafts. METHODS Epigastric vein-to-common femoral artery interposition grafts were performed in male Lewis rats (350 to 450 gm) with standard microsurgical techniques. Grafts were harvested at 1 and 4 hours, 1 and 4 days, and 1 and 2 weeks (n = 5/time). Graft RNA was extracted, reverse-transcribed, and amplified by polymerase chain reaction with sense/antisense primers for TGF-beta 1 and PDGF-A (30 cycles). Polymerase chain reaction fragments were confirmed by Southern hybridization. RESULTS Variable induction of TFG-beta 1 gene transcription was evident in vein grafts at 1 and 4 hours, with prominent mRNA expression from 1 day to 2 weeks. PDGF-A mRNA was detected in ungrafted control veins but was downregulated at 1 hour and absent at 4 hours after grafting. PDGF-A transcription was upregulated by 1 day, with prominent expression from 4 days to 1 week. Early loss of PDGF-A mRNA correlated with the early denudation of the endothelium, whereas upregulation by 4 days was preceded by TGF-beta 1 mRNA expression. CONCLUSIONS Upregulation of TGF-beta 1 and PDGF-A mRNA expression is detected in vein grafts before the development of a quantifiable neointima, which occurs by 2 weeks in our model. This suggests a role for these growth factors in the development of vein graft intimal hyperplasia.

Effect of early plasma transfusion on mortality in patients with ruptured abdominal aortic aneurysm

BACKGROUND The ratio of red blood cell (PRBC) transfusion to plasma (FFP) transfusion (PRBC:FFP ratio) has been shown to impact survival in trauma patients with massive hemorrhage. The purpose of this study was to determine the effect of the PRBC:FFP ratio on mortality for patients with massive hemorrhage after ruptured abdominal aortic aneurysm (RAAA). METHODS A retrospective review was performed of patients undergoing emergent open RAAA repair from January 1987 to December 2007. Patients with massive hemorrhage (≥10 units of blood products transfused prior to conclusion of the operation) were included. The effects of patient demographics, admission vital signs, laboratory values, peri-operative variables, amount of blood products transfused, and the PRBC:FFP ratio on 30-day mortality were analyzed by multivariate analysis. RESULTS One hundred and twenty-eight of the 168 (76%) patients undergoing repair for RAAA received at least 10 units of blood products within the peri-operative period. Mean age was 73.1 ± 9.1 years, and 109 (85%) were men. Thirty-day mortality was 22.6% (29/128), including 11 intra-operative deaths. By multivariate analysis, 30-day mortality was markedly lower (15% vs 39%; P < .03) for patients transfused at a PRBC:FFP ratio ≤2:1 (HIGH FFP group) compared with those transfused at a ratio of >2:1 (LOW FFP), and the likelihood of death was more than 4-fold greater in the LOW FFP group (odds ratio 4.23; 95% confidence interval, 1.2-14.49). Patients in the HIGH FFP group had a significantly lower incidence of colon ischemia than those in the LOW FFP group (22.4% vs 41.1%; P = .004). CONCLUSION For RAAA patients requiring massive transfusion, more equivalent transfusion of PRBC to FFP (HIGH FFP) was independently associated with lower 30-day mortality. The lower incidence of colonic ischemia in the HIGH FFP group may suggest an additional benefit of early plasma transfusion that could translate into further mortality reduction. Analysis from this study suggests the potential feasibility for a more standardized protocol of initial resuscitation for these patients, and prospective studies are warranted to determine the optimum PRBC:FFP ratio in RAAA patients.

Outcomes after endarterectomy for chronic mesenteric ischemia

OBJECTIVES A retrospective study was performed to identify optimal factors affecting outcomes after open revascularization for chronic mesenteric ischemia. METHODS All patients who underwent open surgery for chronic mesenteric ischemia from 1987 to 2006 were reviewed. Patients with acute mesenteric ischemia or median arcuate ligament syndrome were excluded. Mortality, recurrent stenosis, and symptomatic recurrence were analyzed using logistic regression, and univariate and multivariate analysis. RESULTS We identified 80 patients (69% women, 31% men). Mean age was 64 years (range, 31-86 years). Acute-on-chronic symptoms were present in 26%. Presenting symptoms included postprandial pain (91%), weight loss (69%), and food fear and diarrhea (25%). Preoperative imaging demonstrated severe (>70%) stenosis of the superior mesenteric artery in 75 patients (24 occluded), the celiac axis in 63 (20 occluded), and the inferior mesenteric artery in 53 (20 occluded). Multivessel disease was present in 72 patients (90%), and 40 (50%) underwent multivessel reconstruction. Revascularization was achieved by endarterectomy in 37 patients, mesenteric bypass in 29, and combined procedures in 14. Concurrent aortic reconstruction was required in 13 patients (16%). Three hospital deaths occurred (3.8%). Mean follow-up was 3.8 years (range, 0-17.2 years). One- and 5-year survival was 92.2% and 64.5%. Mortality was associated with age (P = .019) and renal insufficiency (P = .007), but not by clinical presentation. Symptom-free survival was 89.7% and 82.1% at 1 and 5 years, respectively. Symptoms requiring reintervention occurred in nine patients (11%) at a mean of 29 months (range, 5-127 months). Multivariate analysis showed that freedom from recurrent symptoms correlated with endarterectomy for revascularization (5.2% vs 27.6%; hazard ratio, 0.20; 95% confidence interval, 0.04-0.92; P = .02). CONCLUSION For open surgical candidates, endarterectomy appears to provide the most durable long-term symptom relief in patients with chronic mesenteric ischemia.