Visceral and renal protection in thoracoabdominal aortic surgery

Abstract

Ischemic renal failure and visceral ischemia are two serious complications of the surgery for thoracoabdominal aortic aneurysm. The introduction of left atrial bypass, partial bypass, total circulatory arrest, and selective visceral perfusion has reduced the incidence of these complications over the past two decades. Yet these complications still persist, suggesting the sub-optimal nature of the available strategies.

Introduction

Thoracoabdominal aortic aneurysm repair (TAAR) presents a significant challenge to the skills of even the most accomplished cardiothoracic surgeon. The vulnerability of the kidney and intestine to the prolonged ischemia due to the aortic cross clamp could potentially affect the outcomes of an excellent technical surgical work. An ischemia time of less than 20 min is positively correlated with better outcomes in these surgeries, with each passing minute adding to the ischemic burden and consequential organ failure.

Data reviewed from a recent series of open TAAR documents the incidence of renal dysfunction to be as high as 20–40% as per the various criteria for acute kidney injury (AKI). Of these, about 2–10% require hemo-dialysis (1). The incidence of AKI steeply increases the early mortality following open TAAR up to 32%, while the initiation of hemo-dialysis further worsens the outcomes with up to 63% mortality [1]. The incidence of chronic kidney disease (CKD) following TAAR affects the long-term survival as well, with reported survival dropping from 74 to 43% at 5-year follow-up as reported by some investigators. Although the incidence of visceral ischemia has been reported to be fortunately rare (up to 7% in TAAR), the consequent mortality rates are high (63%) [1, 2].

Surgical physiology and pathology

Oliguric renal failure in the initial phase after the surgery heralds the onset of renal failure in most cases with progression onto anuric renal shut down and subsequent need for dialysis. It is prudent to aggressively treat the oliguric phase at the outset itself to prevent renal shut down as the initiation of dialysis portends dismal survival in patients undergoing TAAR.

Local and systemic effects of target organ ischemia caused by aortic cross clamping and non-pulsatile extracorporeal circulation (in cases with cardiopulmonary bypass use (CPB)) set off a cascade of inflammatory cytokines with the resultant systemic inflammatory response syndrome (SIRS). The aortic unclamping would lead to ischemia-reperfusion injury to the target organs, which leads to further worsening of the physiology, secondary to free radical mediated cell injury. This reperfusion injury, compounded by systemic inflammatory response, leads to multi-organ failure and mortality [1, 3].

Who are the susceptible individuals?

The various factors contributing to target organ ischemia are summarized in Table 1. The local and systemic effects of aortic clamping and CPB can be modified to some extend by strategizing the conduct of the operation. Maintenance of mean arterial pressure (MAP) above 80 mm of Hg during extracorporeal perfusion (left heart bypass (LHB) or partial bypass) and selective target organ perfusion during surgery are useful techniques in preventing visceral ischemia [4, 5].

Table 1.

Factors contributing to renal and visceral ischemia in TAAA repair

Low GFR

Prolonged CPB time

Emergency surgery

Technical issues

Recent dye injection

Post-operative embolism

Strategizing visceral protection

Pre-operative measures

It is safer to admit these patients a few days before surgery. Most patients at increased risk for post-operative renal dysfunction can be identified before surgery. The following recommendations are evidence based and valid:

1. Stop all nephrotoxic drugs well before the date of surgery.

2. Selective digestive decontamination (SDD) reduces bacterial burden. This limits the bacterial translocation caused by ischemic vascular injury and also prevents intestinal injury [1, 6].

3. Precise reading of the computerized tomography (CT) images.

The quality of the aorta, at the site of cross clamp, should be thoroughly assessed (below the left subclavian artery take off and at D6, D12 levels) [6]. The factors to look for are the severity of atherosclerosis, presence of calcification, or thrombus. The diameter of aorta at D6 and D12 should be noted. Careful consideration of these technical factors would allow safe cross clamping and sequential clamping of thoracoabdominal aorta, negating the risks of systemic embolization and other complications. The identification of the risk factors allows the surgeon to consider alternate methods of aortic occlusion.

• 4.Position of the renal arteries, celiac, superior mesenteric arteries. These vessels are usually near to each other in most cases, and thus, it would be technically easy to include all of them in a single patch to save ischemia time. Appropriate pre-operative planning based on imaging is essential in deciding the strategy for the inclusion of widely separated vessels [7]. Presence of origin stenosis/diffusely diseased renal and visceral arteries, with or without para-aortic disease at arterial take off sites, can render suturing technically demanding [7, 8].
• 5.Intra-operatively visceral perfusion may be optimized using different sizes of balloon tip perfusion catheters and the use of stents/grafts [9]. These should be readily available in the operating room.

Methods of perfusion

Passive shunts were the earliest methods used for maintenance of distal perfusion. Poly-etheylene tubings were used to serve the purpose as passive shunts from proximal to distal infra-renal aorta. Some surgeons have reported using autologous bypass grafts to maintain distal perfusion. The maintenance of a pulsatile and more physiological circulation in the distal perfusion bed is the chief advantage of this technique. However, with this technique, the distal perfusion is solely dependent on proximal pressure head which can be highly variable [6]. The introduction of mechanical circulation has by and large phased out the technique of passive shunting.

Extracorporeal perfusion

The advances in perfusion technology have made life easier for surgeons attempting TAAR. The usual perfusion strategies are LHB, partial bypass, or total circulatory arrest (TCA). These techniques allow a more controlled distal perfusion (however, non-pulsatile) and allow the safe conduct of the proximal anastomosis between the aorta and the graft below the left subclavian take off. If the quality of aorta is permissible for safe clamping at D6 and D12 levels, sequential clamping can be performed to facilitate completion of the implantation of intercostal arteries onto the graft, thereby reducing the ischemia times of the downstream viscera. This, in combination with a mild permissive systemic hypothermia, would afford better visceral protection with a reduced inflammatory load secondary to the extracorporeal perfusion [1, 3].

While employing LHB, the inflow is usually initiated from left superior pulmonary vein with outflow to the left femoral artery with descending aorta clamped. A centrifugal pump is utilized with a prime composition comprising of 500 ml of normal saline, 100 ml of 20% albumin, 5000 units of unfractionated heparin, and a heparin-coated circuit barring the heat exchanger. The proximal and distal pressure heads are maintained at 80 and 70 mm of Hg respectively [6]. Mild hypothermic perfusion strategy is employed to enhance the visceral protection and minimize the effects of SIRS and reperfusion injury. Target activated clotting time (ACT) is set at 200 s with LHB to reduce the incidence of bleeding [6, 7].

An 8-mm graft anastomosed to the left femoral artery, with subsequent cannulation via the graft, ensures distal limb perfusion while performing left heart bypass. This ensures distal limb perfusion and negates the effects of ischemic rhabdomyolysis and the resultant myoglobinuria due to the loss of vascularity caused by direct femoral cannulation. This technique becomes exceedingly important in patients with borderline renal function, who are prone for myoglobinuria-related AKI [8, 9].

At times surgeons encounter difficulty with single lung ventilation during TAAR utilizing left heart bypass, wherein the extracorporeal perfusion may be converted to partial or complete bypass. The femoral artery and vein may be cannulated to institute partial or complete bypass on a case to case basis. If difficulty during femoral venous cannulation is encountered, the right atrium can be made accessible via the thoracotomy incision, by further spreading the ribs (Baylor’s or Thompson’s retractors may serve the purpose) to effect a central right atrial venous cannulation [9].

A hostile aorta, which might preclude a safe cross clamping (calcification, atherosclerosis, dilatation, arch involvement, large aneurysm encroaching chest wall), might necessitate the use of TCA for the safe completion of the procedure. In such cases, the proximal anastomosis between aorta and prosthesis is fashioned on TCA in an “open” clampless fashion, followed by the re-implantation of intercostal arteries from D8 to D11. This would be followed by rewarming and subsequent anastomosis of renal and visceral arteries, as described by Kouchoukos [9]. Deep hypothermia affords excellent visceral protection with the trade-off of post-operative bleeding as its downside.

Selective renal perfusion

Temperature probes are placed in the kidneys and the renal temperatures are maintained between 15 and 22 °C, which gives better ischemic protection, as shown from previous reports [8, 9]. The perfusate comprises of ringer lactate or sodium chloride at 4 °C and mannitol solution (54 ml/8 g). Methyl prednisolone (15 mg) is administered, through appropriately sized perfusion catheters, directly into the exposed left and renal arteries. The induction dose is administered as bolus of 200–300 ml for each kidney followed by a maintenance dose of 100–150 ml every 15 min. The technique of pressure controlled selective renal perfusion (SRP) for better renal protection at 60 mm and 80 mm of Hg, respectively, in cases with or without renal dysfunction, has been described by Jacobs et al. [10]. Some researchers have reported that pulsatile perfusion of the renal arteries incurs less tubular damage [11].

A recent study compared SRP using cold crystalloid solution-based perfusate, further enriched with histidine-tryptophan-keto glutarate in cold ringer lactate. They reported greater freedom from AKI (38.1% vs 9.5%; P = .002) with the enriched crystalloid perfusate [12]. Comparable outcomes in terms of the incidence of AKI in TAAR have been reported in the literature, when utilizing cold crystalloid or cold blood for SRP [13]. However, the use of normo-thermic blood for SRP yielded inferior results in the cold crystalloid or cold blood selective perfusion has been documented, which demonstrates the importance of hypothermia in renal protection [1].

Custodiol, the extracellular cardioplegia solution, when used for SRP has been reported to be associated with lower incidence of AKI [13]. However, the evidence derived from comparative data is lacking, which limits its widespread use. Also, surgeons should be wary of the potential for systemic hypothermia, hemodilution, and electrolyte abnormalities resulting from the larger renoplegia volume, when using Custodiol solution.

Selective visceral perfusion

In contrast to the kidneys, intestines are more tolerant to prolonged ischemic periods before irreversible ischemic damage sets in. Inadequate protection of the intestines could lead to intestinal ischemia with lactic acidosis, luminal bacterial translocation with resultant sepsis, coagulopathy, and multi-organ dysfunction syndrome (MODS). Selective visceral perfusion (SVP) via the celiac and superior mesenteric arteries results in improved micro-circulation of gut resulting in the maintenance of mucosal integrity, lesser bacterial translocation, with lower incidence of acidosis, lower ischemic damage, and inflammation. However, SVP does not fully eliminate the mucosal injury as indicated by the post-operative lactic acidosis, but it serves to reduce the potential for serious ischemic insult to the intestines in TAAR.

The celiac and superior mesenteric arteries are perfused through appropriate sized balloon tipped perfusion catheters with iso-thermic blood from LHB circuit. A strategy of continuous SVP with iso-thermic blood delivered at a flow rate of 300–500 ml per minute had been utilized by some investigators until the re-implantation of visceral arteries was completed during TAAR [13]. They reported lower incidence of intestinal mucosal injury as evidenced by the significantly lower levels of intestinal fatty acid binding protein (IFABP) (713 ± 307.1 vs 170 ± 115.4 pg/ml; P = .014) in patients who received SVP [14].

Ensuring the delivery of SVP

Infrequently, the origins of the renal and visceral vessels might be compromised owing to atherosclerosis or chronic dissection. This will lead to inadequate visceral perfusion and ineffective cooling, with the consequential ischemic damage to viscera. When identified pre-operatively, endarterectomy or stenting of the vessels, either alone or in combination, might ensure adequate visceral perfusion and uniform cooling of the organs, when utilizing SVP during TAAR [15, 16].

Reduction of ischemia time

Increase in the ischemia time (IT) of the kidneys and viscera during TAAR is an important risk factor for AKI and visceral ischemia. The factors causing prolonged ischemic time include technical difficulties, widely separated renal and visceral vessels, which would warrant their individual re-implanatation (Fig. 1), and severe atherosclerotic burden of the visceral arteries, which makes re-implantation and effective delivery of SVP difficult and time consuming [17].

Fig. 1.

Widely spaced visceral vessels—re-implanted individually

If the origin of the renals and the visceral vessels are close to each other, a patch of aorta containing the celiac, superior mesenteric and right renal arteries are attached as an island to the anterolateral aspect of the aortic graft (Fig. 2). In this situation, the left renal artery may be re-implanted separately using a short 6- or 8-mm graft. When the vessel wall is badly diseased, the safer technique would be the use of a hybrid graft—with a nitinol-reinforced self-expanding stent at one end and vascular graft at the other. The nitinol stent containing end may be deployed to the diseased renal and visceral arteries with the prosthetic graft anastomosed to the main aortic graft. This technique is ideally suited for poor-quality aorta, with widely separated visceral and renal vessels, which translates to significant reduction in ischemia time [18].

Fig. 2.

Closely spaced visceral vessels—re-implanted as a single island patch

Additives and protection

The addition of mannitol, methyl prednisone, and heparin in the perfusate is favored by some surgeons and these additives may have a role in ischemic protection of the organs. Mannitol reduces tubular swelling and acts as a free radical scavenger. Recently, the use of atrial natriuretic peptide (ANP), during and after surgery, has been reported to lower the incidence of AKI (30% vs 73% (P = .0014)). This effect might be secondary to the possible renal vasodilation and increased glomerular filtration rate (GFR) associated with the use of ANP. Additionally, ANP acts as an anti-inflammatory agent on renal tubules [19, 20].

Ischemic preconditioning

This is a proposed strategy to protect against the deleterious effects of ischemia/reperfusion injury. Hypothetically, ischemic preconditioning might reduce inflammatory response associated with visceral ischemic injury caused by the cross clamping of the supra visceral aorta. Reduced inflammatory response would lead to improved pulmonary function and translate to shorter intensive unit stay. The supra visceral thoracic aorta is cross clamped for 5 min, followed by unclamping for 5 min. This procedure is repeated twice before applying the cross clamp for prolonged period [18]. The technique of remote ischemic preconditioning, performed at the lower limb arteries, for visceral ischemic protection is currently under investigation [21].

Conclusion

Despite the advances in the strategies for visceral protection in TAAR, the incidence of renal and visceral ischemia still remain as the major predictor of case fatality and significant morbidity and forbear major economic implications. The optimal strategy in visceral protection still remains elusive. More research and surgical ingenuity is called for, in tackling this difficult yet important problem.

Funding

None.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Obtained as per the institutional ethics committee guidance.

Statement of Human and animal rights

Not applicable being a Review article.