Adjunctive Therapy for Spinal Cord Protection During Thoracoabdomina Aortic Aneurysm Repair

Adjunctive Therapy for Spinal Cord Protection During Thoracoabdominal Aortic Aneurysm Repair Ian N. Hamilton.fr and Larry H Hollier Paraplegia. resulting from spinal cord ischemia during thoracoabdominal aortic aneurysm (TAA) repair. continues to be a devastating complication. The incidence of neurological complications. including paraplegia and paraparesis following TAA repair. ranges from 4% to 32% and averages 13% for nondissecting TAA and higher for dissecting TAA. Our current understanding of spinal cord ischemia associated with TAA repair has evolved from animal research and clinical experience . The pathophysiology of spinal cord ischemia is intricately related to three physiological variables. These include the severity and duration of spinal cord ischemia. neuronal reperfusion after reestablishment of spinal cord blood flow. and the neuronal metabolic rate during the ischemic insult. We have developed a multimodality approach to the prevention of neurological deficits. during and after TAA repair. which includes minimizing the severity of spinal cord ischemia. reducing the anticipated reperfusion phenomenon. and lowering the spinal cord metabolic rate. Over the past 16 years. the senior author has undertaken surgical repair of 265 TAAs using a multimodality approach in the protection of spinal cord integrity. In our experience. a combination of adjunctive therapies is critical to minimize the ischemic interval. reduce the neuronal reperfusion injury. and decrease spinal cord metabolism. These techniques have evolved over time. resulting in an overall neurological deficit rate of 4.5% and a neurological deficit at the time of hospital discharge of 1.9%. This article will outline our multimodality approach for spinal cord protection during TAA repair. Copyright © 1998 by W.S. Saunders Company Key words: Paraplegia. spinal cord protection, thoracoabdominal aortic aneurysm repair, neurologic injury, cerebral spinal fluid drainage, distal aortic pump perfusion, reperfusion injury, free radical scavenger.

T

he importan ce of spinal cord blood flow and pressur e has been recognized as a critical physiological param eter related to neurological deficits during proxima l aortic occlusion. Spinal cord perfusion pr essur e is equivalent to th e difference between th e ante rior spinal arterypressure and th e cerebral spinal fluid (CSF) pressure.1 Th er efore, spinal cord perfus ion pr essure may be incr eased either by increasing th e blood pr essure in the spina l artery or by decreasing th e CSF pressure in the th ecal space. Aortic occlusion or cross-clamping result s in From the Department if Surgery, Chattanooga Unit if the College if Medicine, Unioersity if Tennessee, Chattanooga, TN and theDepartment if Surgery, TheMount Sinai Medical Center, TheMount Sinai Hospital, The Mount S inai School ifMedidne, 1 Gustate L Lev)' Place, New Yark, N Y. Address reprint requests to Ian N. Hamilton, J r., MD, Department if Surgery, Chattanooga Unit cf the College '!f Medicine, Unioersuy '!f Tennessee, 979 E ThirdSt, Su ite401, Chattanooga, TN 37403. CO/J)7ight © 1998 fty W.B. Saunders Company 1043-0679/98// 001-0011$08.00/0

distal arterial hypot ension with a decrease in radicular and, therefore, spinal ar te ry perfusion pr essure. In addition, proximal arterial blood pr essure increases during aortic cross-clamping, resulting in increased cardiac afterload and incr eased CSF pressure. The combination of decreased spinal artery perfu sion pr essure and increased CSF pr essure during proxim al aortic occlusion result s in decreased spinal cord blood flow and spinal cord ischemia. This sequence of events may be int errupted by augmenting spinal artery perfu sion pressur e and/or reducing CSF pressur e.

Cerebral Spinal Fluid Drainage

In 1988 McCullough, Hollier, and Nugent showed experime ntally in dogs that CSF drainage before thoracic aortic occlusion decreased the incidence of parapl egia as compared with

S eminars in Thoracic and Cardiovascular Surgery, Vol l O, No 1 (January), 1998: pp 35-39

35

36

Hamilton andHollier

control animals without CSF drainage.I Aortic pressure distal to the aortic cross-clamp was the same in study and control animals; however, spinal cord perfusion pressure was significantly higher in neurologically normal animals compared to those with paraplegia or paraparesis. That same year, Bower et al used isotope-tagged microspheres to determine blood flow to the spinal cord in dogs undergoing aortic crossclamping with and without CSF drainage' CSF drainage significantly improved spinal cord blood flow during aortic cross-clamping in the lower thoracic and lumbar regions. In addition, median spinal cord blood flow more than tripled from baseline blood flow after aortic unclamping in animals without CSF drainage, whereas animals with CSF drainage were protected from this reperfusion hyperemia. CSF drainage provided statistically significant protection from neurological deficit by increasing spinal cord blood flow during aortic cross-clamping and through the attenuation of a reperfusion hyperemia after aortic unclamping. Clinically, some patients undergoing TAA repair were found to awaken with normal neurological examinations only to develop delayed onset paraplegia 1 to 5 days postoperatively. In 1991, Moore and Hollier undertook a study to evaluate the etiology of delayed-onset paraplegia following temporary spinal cord ischemia in an awake rabbit model." They reported a relationship between the duration of ischemia and delayed-onset paraplegia, while controlling for other causes of postoperative paraplegia such as spinal artery thrombosis, embolization, and hypotension. This study provided the foundation of our understanding of ischemia and subsequent spinal cord reperfusion leading to a neurological deficit. Based on this research, CSF drainage was clinically incorporated as part of a multimodality approach to spinal cord protection during TAA repair. This initial clinical experience emphasized complete intercostal artery reimplantation whenever possible, CSF drainage, and maintenance of proximal hypertension during aortic cross-clamping. Additionally, the spinal cord metabolic rate was reduced by moderate hypo-

thermia, intravenous high dose barbiturates, and the avoidance of hyperglycemia. Reperfusion injury was minimized by the use of mannitol, steroids, and calcium channel blockers. Using this multimodality approach, 0 of 42 patients in the protocol group experienced neurological deficit as compared with 6 of 108 (6%) patients in the preprotocol group.' CSF pressure monitoring and drainage, both intraoperatively and postoperatively, for up to 3 days has now become our routine practice during TAA repair. Preoperatively a thoracic epidural catheter is placed for postoperative pain control and a lumbar catheter is introduced under sterile technique into the subarachnoid space (Fig 1). An EDM lumbar catheter (Pudenze-Schulte Medical Corporation, Goletta, CA) with an 80-cm closed tip catheter with 12 side holes is connected to the Becker external drainage and monitoring system (EDMS II) (Pudenze-Schulte Medical Corporation, Goletta, CA) (Fig 2). The Becker EDMS II is a closed system allowing both CSF pressure monitoring and drainage of CSF with an adjustable overflow drainage system. A pressure transducer can be connected to the drainage system stopcock, allowing continuous monitoring ofCSF pressure during and after the operation. The flow chamber on the EDMS II is adjusted to the desired pressure (10 mm Hg in our clinical experience) by sliding the flow chamber along a graduated scale. Thereafter, CSF will drain automatically into the flow chamber and into the collecting bag whenever the CSF pressure exceeds 10 mm Hg. This provides an automatic closed overflow system, decreasing the risk of system contamination and meningitis.

Distal Aortic Pump Perfusion During proximal aortic cross-clamping, spinal artery perfusion pressure may be increased by increasing distal aortic pressure. We and others have incorporated distal aortic pump perfusion as a means of increasing spinal artery perfusion pressure. When added to CSF drainage, spinal cord blood flow is enhanced through manipulation of both variables of the spinal perfusion

Adjunctioe Therapy fir Spinal Cord Protection

37

Figure 1. Patient in left lateral decubitus position after placement of a thoracic epidural cat heter for pain control and lum bar intrathecal catheter for intraoperative and postoperative CSF drainage.

pr essure equ ati on. Distal aortic pump perfusion also reduces left ventricular afte rload, decreases th e risk of perioper ati ve myocardial infarction, and provides perfu sion distal to th e distal aortic cross-clamp. Depending on th e position of th e distal cross-clam p during TAA repair, this may redu ce or eliminat e lower extre mity, visceral, renal, and spinal cord ischemia during periods of proximal aortic reconstruction. This reduction in th e duration of spinal cord ischemia also decreases the risk of a rep erfu sion inju ry and result ant neurological inju ry.6 Th e combination of perioper ati ve CSF drainage and distal aortic pump perfu sion was prospectively evalua ted by Safi et al,? Forty-five consec utive pati ents with type I or II TAA und erwent an eurysm repair with perioperative CSF drainage, distal aortic pump perfusion, and int ercostal artery reattachment. When compared to 11 2 pati ents from th e same cente r tr eat ed without CSF dr ain age a nd dist al aor tic pump perfusion, th e early neurological deficit improved from 31% in th e contro l patients to 9% in th e study grou p. Wh en subdivided according to type, no pati ent with type ITAA experienced

neurol ogical deficit in th e study group versu s

21% in the control group (P = .062). In patients with type II TAA, 13% of th e study group experienced neurological deficit versus 51% of th e control group (P = .0008). The investigators conclud ed that neu rological deficit in patients undergoing treatment for types I and II TAA was significantly redu ced by the combination of perioperative CSF dr ainage and distal aortic pump perfu sion. To reduce th e risk of perioperati ve hemorrh agic complications associated with pump perfusion, we have incorporat ed eithe r left atrialfem oral or femoral-femoral bypass using a centrifuga l perfu sion pump and hep arin-coated extracorporeal circulation (ECC) equipment. The heparin-coated circuitry incr eases the biocompatibility of th e ECC system, reducing or eliminating the need for systemic anticoagulation."

Reperfusion Phenomenon Th e restoration of blood flow, to a pr eviously ischem ic spinal cord, risks a rep erfusion injury.

38

Hamilton andHollier

Hanger Hole-----c>..L:--n System Mountmg Panel-

Instructions for use==1~:;;::~

Pressure Scales Microbialfitter DrtpFormer

Ijl

FlowChamber

locklOlIBrackel

SlidF7::c~~u,:~~~ -tE:7-.L-Jll1f

tal artery reperfusion. We have substituted the intravenous anesthetic agent propofol (Diprivan, Zeneca, Wilmington, DE) for thiopental due to propofol's ability to act as a free radical scavenger with excellent central nervous system distribution.v"!

- = '--

FlowChamber

Connection lme/Manometer Tube

Neuronal Metabolic Rate

FlowChamberSlideClamp

Drainage Bag

Peuentline

ConnectIOn line

Stopcock InJection Sne'"

MaIOSystem Stopcock

MaIOSystem Red

/?=::CI:~~D~e~ad.End Plug-· ~~~~~:}f'

Peuent line

RedEnd

Plug

Patient

Connect/on lme

Microbial

FilterandDrainagePan Cap OneWav-~~

Valve

The last component to our multimodality approach to spinal cord protection is aimed at lowering the neuronal metabolic rate during periods of aortic cross-clamping. We achieve this by allowing the patient's temperature to passively drift to 32° to 34°C, providing moderate systemic hypothermia beneficial for both spinal cord and renal protection. Propofol has also shown its ability to reduce central nervous system metabolic requirements for oxygen while maintaining cerebral oxygenation and autoregulation. 8,g All intravenous fluids are dextrose-free and hyperglycemia is aggressively avoided.

Results Figure 2. The Becker external drainage and monitoring system (EDMS) allows a closed system for CSF drainage and monitoring of CSF pressure. *Mounting bracket on back of panel. **Optional transducer adapter location. (Courtesy of Pudenz-Schulte Medical Corporation, Golletta, CA.)

Many investigators have shown the ability to modulate a reperfusion injury with free radical scavengers, antioxidants, monoclonal antibodies, excitatory neurotransmitter antagonists, opiate receptor antagonists, and calcium channel blockers.f Efforts to reduce the reperfusion injury are initially directed at eliminating or minimizing the primary ischemic insult. This is accomplished with distal aortic pump perfusion, CSF drainage, intercostal artery reimplantation, and expeditious surgery. We modulate the reperfusion phenomenon through the administration of steroids as membrane stabilizers and mannitol as a free radical scavenger. Steroids and mannitol are given before aortic clamping and mannitol is given again preceding intercos-

Our multimodality protocol, for the protection of spinal cord injury during TAA repair, has been progressively introduced in phases over the years as our research and clinical experience have supported the incorporation of additional adjuncts. However, our global incidence of neurological deficit (paraplegia and paraparesis) is 4.5% in 265 patients. The incidence of neurological deficit at the time of hospital discharge is 1.9%. The distribution of neurological deficits is 3 of 40 (7.5%) for type I, 4 of 74 (5.4%) for type II, 40f78 (5.1%) for type III, and 1 of73 (1.4%) for type N TAA.6 Recent literature reviews show postoperative neurological deficits to be associated with early death following TAA repair. 12,13 Therefore, efforts to reduce spinal cord injury during and following TAA repair may also translate into improved mortality rates. Our total mortality rate for the same 265 patients is 7.9% with a 4.5% 30-day rate and a 3.4% operative mortality rate. 6 The complex pathophysiology of neurological injury associated with TAA repair requires the

Adjundioe Therapyfor Spinal Cord Protection

application of a multimodality approach to effectively reduce th e initial ischemic insult, minimize the rep erfu sion phenomenon, and lower th e neuronal metabolic rat e during the period of int errupted aortic flow. CSF drainage continues to be an important adjunct in the multimodality protocol for spinal cord prot ection during TM reparr.

6.

7.

8. 9.

References I. Hollier LH: Protecting the brain and spinal cord.J Vase Surg 5:524-528, 1987 2. McCullough JL, Hollier LH, Nugent M: Paraplegia after thoracic aortic occlusion: Influence of cerebrospinal fluid dr ainage.JVasc Surg 7:153-160, 1988 3. Bower T C, Murray MJ, Gloviczki P, et al: Effects of thoracic aortic occlusion and cerebrospinal fluid dra inage on regional spinal cord blood flow in dogs: Correlation with neurologic outcome.JVascSurg9:135-144, 1989 4. MooreJr. WM, Hollier LH: T he influence of severity of spinal cord ischemia in the etiology of delayed-onset paraplegia. Ann Surg 213:427-432,1991 5. Hollier LH, Money SR, Naslund TC, et al: Risk of spinal cord

10.

II .

12. 13.

39

dysfunction in patients undergoing thoracoabdominal aortic replacement. AmJ Surg 164:210-214, 1992 Hamilton,Jr. IN, Hollier LH: Thoraoabdominal aortic aneurysms, in Moore WS (ed): Vascular Surgery:A Comprehensive Review, ed 5. Philad elphia, PA, Saunders, 1997, pp 417-434 Safi HJ, Bartoli S, H ess KR, et al: Neu rologic deficit in pati ent s at high risk with thoracoabdominal aort ic aneurysms:Th e role of cerebral spinal fluid dr ainage and dista l aortic perfus ion.J VaseSurg20:434-443, 1994 Smith I, White PF, Na thanson M, Gouldson R: Propofol: An update on its clinical use. Anesthesiology 8 1:1005-1043, 1994 Newman MY,MurkinJM, Roach G, et al: Cerebral physiologic effects of burst suppr ession doses of propofol during nonpulsatile cardiopulmonary bypass. CNS subgroup of McSPI. Anesth Analg 81:452-457, 1995 Murphy PC, Bennett JR, Myers DS, et al: The effect of propofol anaesthesia on free radical-induced lipid peroxidation in rat liver microsomes. Eur J Anaesthe siol 10:261-266, 1993 Shyr MJ, Tsai TH, Tan PP, et al: Concen tra tion and regional distrib ution of propofol in brain and spinal cord during propofol anesthesia in the rat. Neurosci Letters 184:212-215, 1995 Panneton JM, Hollier LH: Nondissecting thoracoabdo minal aort ieaneurysms: Part I. Ann Vase Surg 9:503-514, 1995 PannetonJM, Hollier LH : Dissecting descending thoracic and thoracoabdominal ane urysm s: Part II. Ann Vase Surg 9:596605, 1995