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Ann Thorac Surg 2002;73:730-738
© 2002 The Society of Thoracic Surgeons
a The Michael E. DeBakey Department of Surgery, Division of Cardiothoracic Surgery, Baylor College of Medicine, and The Methodist Hospital, Houston, Texas, USA
* Address reprint requests to Dr Coselli, The Michael E. DeBakey Department of Surgery, Division of Cardiothoracic Surgery, Baylor College of Medicine, The Methodist Hospital, 6560 Fannin, Suite 1100, Houston, TX 77030, USA
e-mail: jcoselli{at}bcm.tmc.edu
Presented at the Forty-seventh Annual Meeting of the Southern Thoracic Surgical Association, Marco Island, FL, Nov 911, 2000.
| Abstract |
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Methods. Thirty randomized patients undergoing Crawford extent II thoracoabdominal aortic aneurysm repair with left heart bypass had renal artery perfusion with either 4°C Ringers lactate solution (14 patients) or normothermic blood from the bypass circuit (16 patients). Acute renal dysfunction was defined as an elevation in serum creatinine level exceeding 50% of baseline within 10 postoperative days.
Results. One death occurred in each group. One patient in the blood perfusion group experienced renal failure requiring hemodialysis. Ten patients (63%) in the blood perfusion group and 3 patients (21%) in the cold crystalloid perfusion group experienced acute renal dysfunction (p = 0.03). Multivariable analysis confirmed that the use of cold crystalloid perfusion was independently protective against acute renal dysfunction (p = 0.02; odds ratio, 0.133).
Conclusions. When using left heart bypass during repair of extensive thoracoabdominal aortic aneurysms, selective cold crystalloid perfusion offers superior renal protection when compared with conventional normothermic blood perfusion.
| Introduction |
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In an attempt to prevent this complication and its attendant mortality, several techniques and intraoperative strategies have been suggested, including intraoperative administration of diuretics, minimization of ischemic times, renal hypothermia, and renal artery perfusion with oxygenated blood [1, 8, 9]. Selective blood perfusion of the renal arteries aims to reduce the time of renal ischemia during aortic cross-clamping. Because the viscera and kidneys are perfused with oxygenated blood throughout the period of aortic cross-clamping, the expected reperfusion injury and subsequent organ dysfunction are minimized. Despite the use of this technique, the incidence of kidney failure after TAAA repair ranges from 8% to 29% [1, 3, 10, 11]. In contrast, cold crystalloid renal artery perfusion aims to produce local hypothermia and reduce the metabolic needs of the kidneys [12, 13]. After TAAA repair using cold crystalloid renal artery perfusion, the incidence of renal failure ranges from 3% to 11% [1, 6, 14]. Although many centers treating TAAAs routinely use one of these two methods, the superiority of either method has not been determined by a prospective clinical study. The purpose of this randomized clinical trial was to compare two methods of selective renal perfusioncold crystalloid perfusion versus normothermic blood perfusionand determine which technique provides the best renal protection during TAAA operation.
| Patients and methods |
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Surgical technique
The surgical technique for repair of extent II TAAA has been reported previously in detail [15]. After a thoracoabdominal incision was performed, a myocardial temperature probe (Mon-a-therm, Mallinckrodt Medical, Inc, St. Louis, MO) was inserted in the parenchyma of the left kidney to monitor renal temperature. After systemic heparin administration (1 mg/kg), the left inferior pulmonary vein was cannulated with a 26F USCI aortic right-angled cannula (C.R. Bard, Inc, Tewksberry, MA), and the supraceliac aorta was cannulated with a 20F USCI aortic right-angled cannula (C. R. Bard, Inc). Left heart bypass was achieved with a Nikkiso centrifugal pump (Sorin Biomedical, Irvine, CA) circuit without a reservoir or heat exchanger.
The proximal aortic clamp was applied either above or below the left subclavian artery, and the distal clamp was placed near the sixth intercostal space. Distal aortic perfusion was provided at a rate of 1.5 to 2.5 L/min. The aneurysm was opened between the two clamps, and an appropriately sized gelatin-impregnated polyethylene terephthalate fiber (Dacron) graft was selected. After completing the proximal anastomosis, left heart bypass was discontinued and the distal clamp was removed. The remaining portion of the aneurysmal aorta was opened longitudinally. The distal clamp was not replaced.
For patients randomized to the blood perfusion group, four 9F Pruitt balloon irrigation catheters (Ideas for Medicine, St. Petersburg, FL), connected by means of a multifinger apparatus (Medtronic DLP, Minneapolis, MN), were inserted into the celiac axis, the superior mesenteric artery, and both renal arteries. Continuous perfusion from the bypass circuitat an aggregate rate of 400 mL/minwas provided during intercostal, visceral, and renal artery reattachment (Fig 3). The individual perfusion rate to each vessel was not monitored.
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'' tubing going through a roller head pump. A bolus infusion (400 to 600 mL) of the solution was instilled into the renal arteries, followed by additional intermittent infusions (200 mL) until arterial flow was reestablished. A total of approximately 1.0 to 1.5 L of crystalloid solution was infused in an attempt to achieve a left renal temperature of 15°C. Larger volumes were avoided to limit the potential hazards of fluid overload (indicated by mean pulmonary artery pressure > 30 mm Hg) and severe systemic hypothermia (indicated by nasopharangeal temperature < 31°C).
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Definitions
The extent of aortic graft replacement was defined using the classification of Crawford and associates [14]. Extent II repairs extended from the upper descending thoracic aorta (above the sixth intercostal space) to the infrarenal abdominal aorta. Operations performed within 4 hours of admission because of immediate threat to life were classified as emergent. Perfusion and ischemic times were determined for each of the following regions: right kidney, left kidney, celiac axis, superior mesenteric artery, right leg, and left leg. Left heart bypass times were defined as the time during which a region received normothermic blood from the circuit through the distal aortic cannula. Selective perfusion times were defined as the time during which a region received normothermic blood from the circuit through a balloon perfusion catheter. Total ischemic times were defined as the time between initial aortic clamping and restoration of normal physiologic blood flow to a region. Unprotected ischemic times were defined as a regions total ischemic time minus the time that it received blood during left heart bypass and selective perfusion.
The most recent preoperative serum creatinine value was considered the baseline value. Postoperative renal dysfunction was scored as proposed by Kashyap and colleagues [6]:
2).
Statistical analyses
Data are presented as mean ± standard deviation. Analyses were performed using the SPSS 6.1 software package (SPSS Inc, Chicago, IL). Comparisons between groups were made using Fishers exact test for categorical variables and Students t test for continuous variables. Univariate analysis was used to evaluate preoperative and intraoperative variables for their association with renal dysfunction. All variables with p less than 0.25 on univariate analysis were entered into a multivariate analysis (stepwise logistic regression) to determine which variables were independently predictive of postoperative renal dysfunction.
| Results |
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Ten patients (63%) in the blood perfusion group and 3 patients (21%) in the cold crystalloid perfusion group experienced acute renal dysfunction (p = 0.03), ie, a renal dysfunction score (RDS) of 2 or more (Table 3).
No patients required hemodialysis during the initial 10 postoperative days. Most patients with early renal dysfunction improved by the time they were discharged. Of the 10 patients with acute renal dysfunction in the blood perfusion group, 9 improved (initial RDS, 2
discharge RDS, 1) and 1 worsened (RDS 4
5); the latter patient experienced late kidney failure requiring hemodialysis and died of multiple-organ failure. Of the 3 patients with acute renal dysfunction in the cold crystalloid group, 1 patient improved (RDS 2
1), 1 remained stable (RDS 3
3), and 1 worsened (RDS 2
3) and died.
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| Comment |
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The other widely used intraoperative adjunct is selective renal hypothermia. Experimental data suggest that renal oxygen consumption is reduced to 40% with cooling of the renal parenchyma to 30°C, to 15% at 20°C, and to less than 5% at 10°C [8, 12, 13]. Crawford and coworkers [14] used this technique for the left kidney in many patients undergoing TAAA repair. They attempted to reduce the kidney temperature to 15°C in 70 patients, but accomplished this goal in only half of the cases because the volume of fluid administered had to be limited to prevent fluid overload or severe hypothermia. Svensson and colleagues [18] reported that perfusing both renal arteries with cold crystalloid solution resulted in a significantly lower incidence of renal complications in patients undergoing TAAA repair. Allen and associates [19] reported that there was a significant improvement in discharge creatinine levels in patients treated with renal hypothermia during repair of juxtarenal or suprarenal aortic aneurysms. In our study, reduced kidney temperature provided significant renal protection based on both univariate and multivariable analyses. Although we did not reduce the kidney temperature to less than 15°C in most patients, cold crystalloid perfusion offered superior renal protection when compared with normothermic blood perfusion.
The use of the RDS, based on daily creatinine measurements, as the primary outcome measure is a limitation in our study. Using outcomes that have more substantial clinical relevance, eg, the need for dialysis, requires much larger study populations. The use of more subtle surrogate outcome measures is an expanding trend in clinical trials. By using the RDS as a subtler indicator of renal injury, for example, differences in outcome can be demonstrated with smaller study populations [6]. We agree, however, that it is difficult to know the true clinical significance of the RDS difference in our study. Although not available at the time of this study, we believe that molecular markers of renal injury will improve our ability to demonstrate differences in studies with relatively small numbers of patients. In future trials, we will use several molecular markers, including urinary microalbumin-to-creatinine ratio as an index of glomerular damage, urinary N-acetyl-ß-glucosamine as an index of renal tubular damage, and urinary retinol binding protein-to-creatinine ratio for evaluation of tubular function [20, 21].
The factors that contribute to renal dysfunction after TAAA repair include ischemia reperfusion injury, nonpulsatile flow in perfusion systems, transfusion of blood products, atheroembolism, and dissection of the renal artery. The multifactorial nature of renal injury mandates a multimodality approach to renal protection. In light of the differing benefits of blood perfusion and cold crystalloid perfusion, the next logical step is a combined approach, ie, cold blood perfusion [11]. A trial comparing cold blood and cold crystalloid perfusion is underway.
| Discussion |
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DR COSELLI: Yes.
DR WEIMAN: Do you perfuse the legs at the same time or do you just come off of that into your branch vessels?
DR COSELLI: In this particular group of patients, what we would do is come off left heart bypass as we took off the distal clamp and remove the distal cannula. All of the distal perfusion cannulas were placed in the lower descending thoracic aorta just above the celiac access. So then we would shut down all the flow distally. We would restart left heart bypass into the celiac and super mesenteric arteries in all cases, and what we were doing was randomizing the cold perfusion of the kidneys versus continued blood perfusion from the left heart blood. So there was no perfusion of the legs in any case after the left heart bypass was initially discontinued.
DR JAKOB VINTEN-JOHANSEN (Atlanta, GA): That was a very nice presentation. Have you used any adjunctive antiinflammatory therapy, specifically for the kidneys, such as leukocyte depletion or adenosine, nitric oxide, something like that, that would attenuate the effect of inflammatory cells triggered at reperfusion?
DR. COSELLI: No, we have not done so clinically. We are looking at some of those techniques in the lab, and this is obviously a very preliminary, embryonic study. There are multiple permutations on renal protection that can be derived, again, hopefully through some randomized prospective studies, to answer some of these questions, but, no, we have not used them clinically.
The problem we have run into is that in some patients we were using cold, some patients we were using warm, and retrospectively evaluating it, it was a bit difficult to determine exactly which of the two techniques was better. So we set on this study to try to sort out the difference and found that the cold was better.
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