Cerebral and Organ Protection
Hypothermic Cardiopulmonary Bypass and Circulatory Arrest
in the Management of Thoracoabdominal Aortic Disease
PRINCIPLES OF CEREBRAL PROTECTION DURING OPERATIONS ON THE THORACIC AORTA
The brain is one of the most sensitive organs to ischaemia. Three principles of protection apply:
Always perfuse anterograde at an appropriate rate, if at all possible, even if low flow. Options for anterograde include brachial, axillary, and selective cerebral perfusion. When using anterograde and the arch is open always make sure that the left subclavian is occluded to make sure the vertebral system remains pressurised. If anterograde is not possible then retrograde is better than nothing.
Pharmacological protection of the brain relies on barbiturates, and propofol. BIS monitoring may play a role to confirm no or minimal cerebral electrical activity. The evidence base for this practice remains small though.
Temperature reduction via core cooling via CPB and topical cooling, mainly to prevent rewarming, via packing the head in ice also remain important tools to reduce the metabolic and hence oxygen requirements of the brain. (Q10 is the reduction in metabolic rate that occurs when the temperature falls by 10oC, usually about 50%).
The method of ABG analysis ie pH stat verses alpha stat also may contribute to cerebral damage / protection. Debate continues, although alpha stat is thought to be superior.
Pulmonary protection can be divided up into two time periods, intraoperative and postoperative.
Intraoperative pulmonary protection can be achieved by a number of different techniques:
Venting the lungs to prevent excessive pulmonary capillary pressure,
Care with manual handling of the lung particularly the left lung in thoracoabdominal work,
Minimising the use of blood products if at all possible, and
Possible use of Aprotinin to prevent neutrophil activation and inflammation during CPB
Renal dysfunction and failure requiring mechanical support remains a common problem after aortic surgery. A number of different strategies can aid in its prevention:
Maintaining an adequate blood pressure, particularly in the elderly patient who is used to running at higher pressures. Noradrenaline can be particularly helpful, here when cardiac output is adequate.
Maintain an adequate cardiac output. When the cardiac output falls renal and mesenteric blood flow are the first two organ systems to vasoconstrict and have reduced blood flow to help maintain perfusion of the other organ systems of the body. Adrenaline should probably be the first line inotrope when primary myocardial contractility is a problem. Haemodynamic monitoring via Swann-Ganz catheter or non-invasive monitoring via the exhaled CO2 should be instigated earlier rather than later.
Maintaining fluid balance is necessary for two reasons. Firstly to maintain adequate cardiac output and secondly to keep the CVP and low as possible, since renal perfusion pressure equals mean arterial pressure minus CVP (not much when MAP is 55 to 60 and CVP is 20!).
Haemoglobinuria and to a lesser extent myoglobinuria occur after procedures with prolonged cross clamp times and in cases of circulatory arrest. Both these agents are nephrotoxic. Encouraging urine output via the liberal use of frusemide, mannitol and dopamine, may help prevent crystallisation in the nephrons. Urine alkalisation with bicarb is not routinely utilised.
Eternal catches:
Gastrointestinal protection can be achieved via a number of
different mechanisms at different time points:
Adequate blood pressure and cardiac output remain paramount.
The combination of low cardiac output, large doses of
vasopressor drugs in a patient with generalised arteriosclerosis who is bleeding
and receiving clotting factors while hypotensive is a recipe for disaster ie
bowel ischaemia on days 5 to 7, when apparently starting to get better.
The role of dopexamine remains controversial amongst even
anaesthetists.
Early institution of enteral feeding has been shown to be beneficial in a number of studies. Glutamate deficiency of GUT epithelium is thought to predispose to increased permeability to bacteria and endotoxins, which cause SIRS, bacteraemias and septicaemias. Feeding can start immediately post operatively, the waiting for bowel sounds and bowel movements in the absence of a bowel anastomoses is unnecessary. Obviously small volume feeds are utilised initially.
The use of gastric tonometry seems top have fallen away.
Peripheral limb ischaemia can be a major source of morbidity and mortality via myoglobinuria and even amputation. Two key points are:
Don’t snare femoral artery and vein when cannulating the groin as this causes leg ischaemia distal to the cannulation site.
Tight bandages on the leg that the vein was harvested from, if CABG was also performed, can result in ischaemia.
The combination of low cardiac output, large doses of vasopressor drugs in a patient with generalised arteriosclerosis who claudicates, who is bleeding and receiving clotting factors while hypotensive is a recipe for limb ischaemia.
The insertion of an IABP into the same leg that has a femoral dialysis catheter inserted also posses a risk via reduction in inflow and outflow from the limb, especially if the patient claudicates in this limb.
The combination of the above three points makes limb ischaemia almost certain.
Vascular Anatomy of the Spinal Cord
Pathophysiology of Aortic Cross-Clamping
Pathophysiology of Spinal Cord Ischaemia
SPINAL CORD PROTECTION DURING OPERATIONS OF THE THORACIC AORTA
Spinal cord protection remains a hotly debated subject. Spinal cord protection remains only of relevance during thoracoabdominal work. The following points are however important, though their relative importance almost certainly varies from case to case, fuelling the debate of their relative merit.
Maintaining an adequate blood pressure to ensure spinal perfusion, even if a number of intercostals have been tied off, remains important intraoperatively and postoperatively. Indeed should late paraplegia occur post thoracoabdominal surgery, raising the blood pressure remains an important therapy.
Spinal artery reimplantation is variably performed, via the use of an overlay patch graft. Spinal arteries that are actively bleeding when the aorta is open have a good collateral circulation by definition so can be over sewn. Intercostals that are included in the patch overlay graft are usually the biggest seen and the most easily accessible when the aorta is open. Identification of the artery of Adamkiewitz, remains virtually impossible at operation. The underlying aortic aneurysm extent and pathology almost certainly dictates whether this technique is useful, and the risk of spinal paraplegia to the patient.
Hypothermia remains an important technique in spinal cord protection. Local cooling both topical and intraspinal via “spinal plegia” have been utilised, however systemic cooling via CPB remains the most common technique. The optimum temperature is unknown, but 14 to 16oC seems to be the most common temperature range used.
CSF drainage both intraopertively and postoperatively remains the most controversial point in spinal cord protection. The mechanism is postulated that the skull and spinal canal are rigid bony canals and that CSF pressure impedes venous outflow from the “skull and spinal box”, so lowering the pressure, but avoiding conning will ensure spinal cord blood flow should the spinal arteries flow be diminished for any reason. No clinical studies have demonstrated any superior benefit of this technique. However a number of case reports of late onset paraplegia post thoracoabdominal aneurysm repair have reported that the combination of CSF drain (re)insertion and increased blood pressure have reversed the paraplegia as long as the CSF drainage has been promptly instituted.
Evoked potentials is a technique where stimulation of the brain and elicitation of a motor response can be used to evaluate spinal cord ischaemia. The motor response and not the sensory response is used because the anterior spinal artery supplies the motor part of the spinal cord.
A number of pharmacological agents utilised both intravenously and intrathecally have been tried but none are used clinically on a routine basis.
The risk of paraplegia depends on the extent, and position of the aneurysm
Edmunds Chapter
PARAPLEGIA AND SPINAL CORD PROTECTION STRATEGIES
Irreversible paraplegia is one of the most devastating complications after TAAA repair. The incidence of paraplegia or paraparesis, as reported in the literature, following thoracoabdominal aortic aneurysms varies substantially and ranges from 4% to 32%. Svensson et al's landmark report of Crawford's experience documented on overall 16% incidence of paraplegia or paraparesis; complete paralysis occurred in more than half of patients with deficits. In the author's report of 1108 patients who underwent elective repair, the combined incidence of paraplegia/paraparesis was 3.6% (40 of 1099 patients, excluding 7 patients with preoperative paraplegia and 2 patients who died during operation). Generally, in large series the incidence of paraplegia and paraparesis is equally divided. Up to 30% of patients who develop postoperative neurologic deficits initially awake with lower extremity function but develop deficits subsequently, i.e., "delayed paraplegia." Operative factors that contribute to spinal cord injury include the duration and degree of ischemia, reperfusion injury, and loss of critical intercostals and lumbar arteries due to ligation, embolization, or thrombosis. The risk of spinal cord injury averages, based on the Crawford classification, 13% for extent I, 28% to 31% for extent II, 7% for extent III, and 4% for extent IV. Although in the past aortic dissection was identified as a risk factor, in more recent experience, dissection is no longer a risk factor for the development of postoperative paraplegia or paraparesis. This is primarily a consequence of aggressive reattachment of intercostal arteries in patients with aortic dissection. This effort to reattach intercostal arteries has also likely reduced the risk of delayed paraplegia.
Vascular Anatomy of the Spinal Cord
The anatomy of the blood supply to the spinal cord is relevant to prevention of spinal cord ischemia and its sequelae. The major arterial circulation to the spinal cord is the anterior longitudinal spinal artery and the paired posterior longitudinal spinal arteries. These vessels originate from intracranial vertebral arteries, or branches thereof, and course along the spinal cord for its entire length. The segmental spinal arteries supplying the thoracic and lumbar regions of the cord originate from the posterior branches of the intercostal and lumbar arteries, respectively. The anatomy is highly variable from one individual to another. The segmental spinal arteries give rise to the large anterior and smaller posterior radicular arteries. Each then directly supplies the anterior and posterior longitudinal spinal arteries. Not all anterior and posterior radicular arteries, however, reach the cord. It is this fact and the fact that the anterior spinal artery frequently is attenuated, or entirely discontinuous, that makes the spinal cord highly vulnerable to ischemia. The artery of Adamkiewicz is the largest of the radicular medullary arteries. It has a variable origin, arising between T5 and T8 in 12% to 15% of the cases, between T9 and T12 in 60%, at L1 in 14%, at L2 in 10%, at L3 in 1.4%, and between L4 and L5 in 0.2%. The arteria radicularis magna anterior is a decisive factor influencing spinal cord damage during aortic occlusion. When the vessel reaches the anterior spinal artery, generally it bifurcates into a smaller ascending branch and a larger descending branch. Intimal atherosclerosis, particularly in medial degenerative fusiform aneurysms, obliterates many intercostal and lumbar arteries, and complicates matters anatomically.
Pathophysiology of Aortic Cross-Clamping
An understanding of the pathophysiological mechanisms involved in aortic cross-clamping and unclamping is imperative in selecting effective measures to prevent and treat the consequences. Most clinical studies indicate that cardiac output decreases with thoracic aortic cross-clamping, whereas most animal studies show no significant change. The normal heart can withstand large increases in afterload without significant ventricular distention or dysfunction. Although impaired myocardial contractility and reduced coronary reserve are rare in animal experiments, such disorders are frequent in the elderly population undergoing aortic reconstruction. Clamping the aorta increases impedance to aortic flow, increases systemic vascular resistance and afterload, and redistributes blood volume because venous vasculature distal to the aortic clamp collapses and constricts. This effectively increases preload. The increases in afterload and preload demand an increase in myocardial contractility, which causes an autoregulatory increase in coronary blood flow. Impaired subendocardial perfusion caused by high intramyocardial pressure, with resultant acute deterioration in left ventricular function and/or myocardial ischemia, may be the cause of wall motion abnormalities and changes in ejection fraction. If coronary blood cannot increase, cardiac decompensation follows.
Pathophysiology of Spinal Cord Ischemia
Injurious effects to the spinal cord, kidneys, lungs, and abdominal viscera are caused primarily by ischemia and reperfusion of organs distal to the aortic clamp and to a release of mediators from ischemic and reperfused organs. The most challenging and troublesome complication following TAAA replacement remains spinal cord injury and the development of paraplegia or paraparesis.
Spinal cord ischemic injury is the result of permanent or temporary interruption of spinal cord blood supply during aortic cross-clamping and permanent disruption of delicate and variable arteries to the spinal cord. Several pathogenetic mechanisms are related to neuronal cell death after transient spinal cord ischemia: excitotoxicity, intracellular calcium overload, nitric oxide, eicosanoids, apoptosis, inflammation, and reactive oxygen species. These mechanisms should be regarded as pathways that act in both parallel and sequential manners. The duration of cross-clamping influences the magnitude of spinal cord ischemia and reperfusion. Studies suggest that cross-clamping for a period of less than 30 minutes is frequently safe. Thoracic aortic occlusion results in increased intracerebral blood flow, which contributes to the increased CSF pressure and decreased spinal cord perfusion pressure. By reducing CSF pressure, therefore, CSF drainage theoretically improves spinal cord perfusion during periods of thoracic aortic clamping.
An alternative explanation proposed by Piano and Gewertz postulates that increased CSF pressure during aortic clamping is related to volume changes in the venous capacitance beds located in the dural space. Based on this model, the benefit of CSF drainage may be related to enhanced patency of these intramural veins. Other authors have suggested that the protective effect of CSF drainage may be attributable to the removal of negative neurotrophic factors that accumulate in the CSF during the ischemic period. Brock et al, for example, observed a strong positive relationship between elevations of CSF excitatory amino acid levels (i.e., glutamate, aspartate, and glycine) during aortic cross-clamping and reperfusion, and subsequent development of clinical signs of spinal cord injury. Our recent prospective randomized trial focused solely on the impact of CSF drainage in preventing neurologic deficits after TAAA repair. The control and treatment groups were extremely well matched and a consistent surgical strategy was used throughout the study. The trial clearly showed that CSF drainage prevents paraplegia after the repair of extent I and II TAAA.
Sodium nitroprusside during thoracic aortic cross-clamping reduces spinal cord perfusion pressure and increases the incidence of neurologic deficits. The decrease in cord perfusion pressure is owing to a decrease in the distal aortic pressure beyond the clamp and an increase in CSF pressure. The increase in CSF pressure occurs from cerebrovasodilatation. Drugs to reduce proximal aortic pressure ideally should possess minimal cerebrovasodilating properties.
The neuroprotective effect of hypothermia is presumed to be secondary to decreased tissue metabolism and a generalized reduction in energy-requiring processes in the cell. However, the mechanisms may be more complex and involve membrane stabilization and reduced release of excitatory neurotransmitters. The author uses mild passive hypothermia (31°C-33°C) in all cases. Frank et al report a technique using partial bypass and moderate hypothermia for organ protection during the clamp-induced ischemic period. The advantages of moderate over deep hypothermia include a stable intrinsic cardiac rhythm that eliminates the need for full cardiopulmonary bypass. They report a series of 18 patients undergoing thoracic and thoracoabdominal aortic aneurysm resection and replacement with moderate (30°C) hypothermia and partial bypass (aorto-femoral or atrio-femoral). No patient developed paraplegia or significant renal failure. There were two deaths (11%). The advantages of moderate over deep hypothermia include a stable intrinsic cardiac rhythm that eliminates the need for full cardiopulmonary bypass. Most authors specifically avoid the technique of profound hypothermia and circulatory arrest for TAAA repair, principally because of the threat of coagulopathy, pulmonary dysfunction, and massive fluid shift.
Crawford et al reported the clinical use of cardiopulmonary bypass using hypothermic circulatory arrest in 25 patients treated for thoracic aortic aneurysms through a posterolateral approach. There were 21 early survivors and cerebral protection was entirely satisfactory. The technique was not entirely effective in eliminating paraplegia; 2 (11%) of 18 patients at risk for ischemic spinal cord injury developed neurologic deficits. This may be explained by satisfactory cord protection during the period of ischemia, but spinal cord injury from sacrifice of critical intercostal arteries.
Kouchoukos et al have recently reported on the use of hypothermic cardiopulmonary bypass with circulatory arrest as an adjunct for operations on the distal aortic arch, descending thoracic aorta, and thoracoabdominal aorta. They evaluated 161 patients. Their 30-day mortality rate was 6.2%, and 90-day mortality rate was 11.8%. Paraplegia occurred in 4 and paraparesis in 1 of 156 operative survivors. Renal dialysis was required in 4 (2.5%). They identified hypothermic cardiopulmonary bypass as providing safe and substantial protection against paralysis and renal, cardiac, and visceral organ system failure.
There are two variations of regional spinal cord hypothermia reported in the literature: direct installation of cold perfusate into the epidural or intrathecal space, and intravascular cold perfusion into isolated thoracic aortic segments with the intention that the cold perfusate will be delivered through the intercostals vessels to the spinal cord. Epidural cooling for regional spinal cord hypothermia in the dog model is effective in preventing paraplegia following aortic cross-clamping. Davidson et al reported a clinical trial of epidural cooling in eight patients undergoing thoracoabdominal aortic replacement for aneurysm. The technique satisfactorily achieved regional spinal cord hypothermia and adequate protection. Cold perfusion into isolated aortic segments has been used in animal models, with demonstration that cord temperature can be rapidly and effectively diminished.
Intuitively, sacrifice of intercostal or lumbar arteries that are critical to the direct blood supply of the spinal cord is a significant factor in the development of postoperative paraplegia. Maintenance of flow through such arteries during all or part of the anatomical repair potentially keeps the period of spinal cord ischemia within the generally safe 30 minutes. This concept is supported by a meta-analysis of the literature reported by von Oppell in a review of 1742 patients treated for traumatic aortic rupture over a 25-year period. Simple aortic cross-clamping produces an incidence of paraplegia of 19.2%, whereas shunting reduces the incidence of paraplegia to 11.1%. Active augmentation of distal aortic perfusion, i.e., left atrial to femoral artery bypass or femoro-femoral bypass, has the lowest incidence of new postoperative paraplegia at 2.3% (p < .00001). The cumulative risk of paraplegia increases substantially if the duration of aortic cross-clamping exceeds 30 minutes, but only when distal perfusion is not augmented (p < .00001). In using left heart bypass for distal perfusion during replacement of descending thoracic and thoracoabdominal aortic aneurysms, Borst et al found that the technique effectively unloads the proximal circulation during aortic occlusion and maintains adequate perfusion of distal vital organs to reduce early mortality and renal failure. Further, the risk of spinal cord damage decreased with combined distal perfusion and aggressive reattachment of distal intercostal arteries. Clearly, the devastating complication of paraplegia and other organ failure secondary to ischemia is worthy of further research; however, a combination of measures including distal aortic perfusion, aggressive reattachment of intercostal arteries, hypothermia, avoidance of hyperglycemia, and CSF drainage has substantially reduced this devastating complication.
Motor evoked potential (MEP) monitoring has the potential to specifically reflect motor function and motor track blood supply during the period of aortic cross-clamping. MEP uses stimulation of the motor cortex or motor neurons and usually records from a peripheral muscle. In 1997, Haan et al described the technique of transcranial stimulation of the motor cortex with recording of lower extremity myogenic potentials to detect intraoperative spinal cord ischemia. Transcranial stimulation has not yet been approved by the Food and Drug Administration. The method requires special anesthetic techniques, since complete neuromuscular blockade is incompatible with myogenic MEP monitoring. In addition, this technique is generally used in conjunction with left atrium to femoral artery bypass. Recently, Jacobs et al published an excellent series of 184 patients undergoing TAAA repair in which they used a protocol that included left heart bypass, cerebrospinal fluid drainage, and the monitoring of MEPs. They found that MEP was a sensitive technique for the assessment of spinal cord ischemia and the identification of the segmental arteries that critically contributed to spinal cord perfusion. They were able to reduce their incidence of neurologic deficit to less than 3%.