European Journal of Cardio-thoracic Surgery 31 (2007) 643—648 www.elsevier.com/locate/ejcts
Spinal cord perfusion after extensive segmental artery sacrifice: can paraplegia be prevented?§ Christian D. Etz a,*, Tobias M. Homann a, Konstadinos A. Plestis a, Ning Zhang a, Maximilian Luehr a, Donald J. Weisz b, George Kleinman c, Randall B. Griepp a a
Department of Cardiothoracic Surgery, Mount Sinai School of Medicine, New York, New York, USA b Department of Neurophysiology, Mount Sinai School of Medicine, New York, New York, USA c Department of Pathology, Mount Sinai School of Medicine, New York, New York, USA
Received 10 September 2006; received in revised form 28 December 2006; accepted 5 January 2007; Available online 12 February 2007
Abstract Objective: Understanding the ability of the paraspinal anastomotic network to provide adequate spinal cord perfusion pressure (SCPP) critical for both surgical and endovascular repair of thoracoabdominal aortic aneurysms (TAAA). Methods: To monitor pressure in the collateral circulation, a catheter was inserted into the distal end of the divided first lumbar segmental artery (SA) of 10 juvenile Yorkshire pigs (28.9 3.8 kg). SA pairs from T3 through L5 were serially sacrificed at 32 8C; SCPP and function — using motor-evoked potentials (MEPs) — were continuously monitored until 1 h after clamping the last SA. Intermittent aortic and SCPP monitoring was continued for 5 days postoperatively, along with evaluation of motor function. Results: A mean of 14.4 0.7 SAs were sacrificed without loss of MEP. SCPP (mmHg) dropped from 68 7 before SA clamping (77% of aortic pressure) to 22 6 at end clamping, and 21 4 after 1 h, reaching its lowest point — 19 4 — after 5 h. Postoperatively, SCPP recovered to 33 6 at 24 h; 42 10 at 48 h; 56 14 at 72 h; 62 15 at 96 h, returning to baseline (63 20) at 120 h. Despite comparable SCPP patterns, four pigs did not fully regain the ability to stand. Six animals recovered: two could stand and four could walk. Conclusions: Interruption of all SAs at 32 8C in this pig model results in a spectrum of cord injury, with normal function in a majority of pigs postoperatively. The short duration of low SCPP suggests that hemodynamic manipulation lasting only 24—48 h may allow routine complete preservation of normal cord function despite sacrifice of all SAs. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. Keywords: Spinal cord perfusion/protection; Paraplegia; Segmental artery sacrifice; Thoracoabdominal aortic aneurysm repair (TAA/A)
1. Introduction The mortality and morbidity of even extensive thoracoabdominal replacement has improved markedly in recent years [1]. However, postoperative paraplegia remains a devastating complication and its occurrence is still somewhat unpredictable [2—6]. Most often, neurologic injury becomes apparent immediately postoperatively, and is attributed to ischemic injury during intraoperative aortic cross-clamping and/or inadequate postoperative spinal cord perfusion. However, a small fraction of patients awaken from anesthesia neurologically normal, but develop delayed onset paraplegia hours to weeks later. The pathogenesis of both types of paraplegia, but § Presented at the joint 20th Annual Meeting of the European Association for Cardio-thoracic Surgery and the 14th Annual Meeting of the European Society of Thoracic Surgeons, Stockholm, Sweden, September 10—13, 2006. * Corresponding author. Address: Mount Sinai School of Medicine, Department of Cardiothoracic Surgery, One Gustave L. Levy Place, PO-Box: 1028, New York, NY 10029, USA. Tel.: +1 212 659 6800; fax: +1 212 659 6818. E-mail address:
[email protected] (C.D. Etz).
particularly of delayed onset deficit, is still poorly understood [7]. Consequently, the effectiveness of different strategies for minimizing intraoperative spinal cord ischemia, and for managing intercostal and lumbar arteries during repair of thoracic and thoracoabdominal aortic aneurysms (TAA/A) in order to prevent paraplegia remains controversial [3,8—14]. The studies described in this report were undertaken to try to gain a better understanding in an animal model of the impact of extensive sacrifice of segmental arteries (SAs) on spinal cord perfusion intraoperatively and in the immediate postoperative period, under experimental conditions which approximate the circumstances prevailing during clinical thoracoabdominal aortic surgery. Previous studies with this model established the feasibility of routine extensive SA sacrifice without loss of function because of the existence of a dense and complex collateral arterial network feeding the spinal cord [15,16]. It is hoped that further investigation of the usual physiological and functional response of the collateral spinal cord perfusion network to the sacrifice of important contributors to its blood supply — and especially of
1010-7940/$ — see front matter # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.ejcts.2007.01.023
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C.D. Etz et al. / European Journal of Cardio-thoracic Surgery 31 (2007) 643—648
the time course of the response — will help to elucidate how best to prevent even the rare occurrence of paraplegia after extensive SA sacrifice. Avoiding spinal cord injury despite occlusion of most SAs is critical not only for surgical repair but also for the eventual successful endovascular treatment of large thoracoabdominal aneurysms.
2. Materials and methods 2.1. Study design Ten female juvenile Yorkshire pigs (Animal Biotech Industries, Allentown, NJ, USA), 4—5 months of age, weighing 28—32 kg, were used for this experiment. In all animals, the descending thoracic and abdominal aortas were exposed, and all segmental arteries were carefully dissected. Thereafter, the segmental artery feeding L1 was identified and clamped proximally, and an arterial catheter was placed for monitoring spinal cord perfusion pressure (SCPP), generated by flow in the collateral pathway. With the L1 catheter in place, all thoracic and abdominal segmental arteries were sequentially clamped in a craniocaudal direction during mild hypothermia (32 8C), allowing a 3-min interval between clamping of successive arteries. In addition to hemodynamic variables — arterial pressure and SCCP — myogenic motor-evoked potentials (MEPs) were monitored. Functional recovery was evaluated for 5 days using a modification of the Tarlov score, and histopathological examination was carried out after sacrifice. This experimental model closely simulates the procedure used for resection of descending thoracic and thoracoabdominal aneurysms clinically at our institution. However, it should be noted that the anatomy of the pig differs from that of humans in having 13 thoracic (and five lumbar) segmental arteries, which arise together from the descending aorta and subsequently divide. The subclavian arteries and the median sacral arteries are both important parts of the collateral perfusion of a continuous spinal cord vascular network in both species; in humans, however, the iliac arteries provide a much greater proportion of the flow into the collateral network. In the clinical situation, cross-clamping of the aorta is occasionally required for an open distal anastomosis, and distal perfusion and spinal fluid drainage are routinely utilized to minimize intraoperative spinal cord ischemia. This experimental model is simplified to allow an uncomplicated focus on the input to the collateral network in the wake of segmental artery sacrifice. Previous experiments with this model have demonstrated that the spinal cord collateral flow in the pig behaves in ways very similar to what is observed under comparable circumstances clinically in humans [15,16]. 2.2. Perioperative management and anesthesia All animals received humane care in compliance with the guidelines of ‘Principles of Laboratory Animal Care’ formulated by the National Society for Medical Research and the ‘Guide for the Care and Use of Laboratory Animals’ published by the National Institute of Health (NIH Publication No. 8823, revised 1996). The Mount Sinai Institutional Animal Care
and Use Committee approved the protocols for all experiments. After pretreatment with intramuscular ketamine (15 mg/ kg) and atropine (0.03 mg/kg), animals were anesthetized with intravenous sodium thiopenthal (20 mg/kg). Following endotracheal intubation, the pigs were ventilated mechanically with an FiO2 of 0.5 and anesthesia was maintained with an infusion of ketamine 15 mg/kg/h and sufentanil 5 mg/kg/h. This anesthetic regimen has no major effect on MEP responses, and has been described previously [12]. Paralysis for intubation was achieved with intravenous pancuronium (0.1 mg/kg), but no further doses were administered subsequently to avoid interfering with measurement of MEPs. The ventilator rate and the tidal volume were adjusted to maintain the arterial carbon dioxide tension at 35—40 mmHg. End-expiratory carbon dioxide (PPG Biomedical Systems, Model 2010-200 R, Lenexa, KS, USA) was monitored continuously. Arterial oxygen tension was maintained >90 mmHg. A bladder catheter (Foley 8—10 F) was inserted for online measurement of urine output, and temperature probes were placed in the esophagus and the rectum. Electrocardiographic measurements were recorded continuously. An arterial line was placed in the right brachial artery for pressure monitoring and blood sampling (pH, oxygen tension, carbon dioxide tension, oxygen saturation, base excess, hematocrit, hemoglobin and glucose, lactate, Blood Gas Analyzer, Ciba Corning 865, Chiron Diagnostics, Norwood, MA, USA). 2.3. Body temperature management After inducing anesthesia (see protocol above), the pigs were cooled to 32 8C rectal temperature by covering them with packs of artificial refrigerants for a period of 30 min. In addition, a cooling blanket was used even after the target temperature was reached to maintain hypothermia and prevent an upward temperature drift during the procedure. The operating room temperature was reduced to 14 8C. No local cooling of the vertebral column was undertaken. The animals were subsequently warmed using a heating blanket and a heating lamp, usually for 90—100 min, and by raising the operating room temperature to 24 8C. To prevent any intraoperative temperature drift, the small left thoracotomy in the fourth intercostal space was temporarily closed after clamping the thoracic spinal arteries. 2.4. Monitoring of postoperative systemic and spinal cord perfusion pressure (SCPP) Two arterial lines were placed: one in the descending aorta and another in the distal arm of the segmental artery feeding the first lumbar segment. These lines enabled systemic and lumbar perfusion pressure monitoring and blood sampling (pH, oxygen tension, carbon dioxide tension, oxygen saturation, base excess, hematocrit, hemoglobin and glucose, lactate; Blood Gas Analyzer, Ciba Corning 865, Chiron Diagnostics, Norwood, MA, USA) prior to, during, and after radical sacrifice of all thoracic and abdominal segmental arteries.
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2.5. Monitoring technique for motor-evoked potentials (MEPs) A 5 cm longitudinal incision was made in the scalp overlying the skull, and the periosteum was removed to expose the sagittal and coronal sutures of the calvarium. Four stainless steel screw electrodes with attached wire leads were screwed into the skull 10 mm lateral to the sagittal suture. Two screws were placed on the left side (8 mm anterior and 8 mm posterior to the coronal suture), and two were equally placed on the right. The wire leads were connected to an electrical stimulator (Digitimer Stimulator Model D 180A, Welwyn, Garden City, United Kingdom). Electromyographic recordings were made from sterile stainless steel needle electrodes placed through the skin over the tibialis muscle in the hind leg and the muscles in the foreleg. A stimulation train (three pulses, 200—300 V, 100 ms pulse duration, and 2 ms interstimulus interval) delivered to the skull electrodes was used to elicit MEPs. MEPs were amplified (gain 2000), bandpass filtered (10—1000 Hz), digitized, and stored on an optical disk for subsequent analysis by a Spectrum 32 neurophysiological recording system (Cadwell Laboratories Inc., Kennewick, WA, USA). MEPs were recorded before clamping, during the 3-min interval after clamping of each segmental pair, and after clamping of all thoracic and abdominal segmental arteries for a period of 60 (to 90) min. The baseline value was determined just prior to the start of SA clamping. A lack of response to the stimulus is considered evidence of ischemic spinal cord injury. Data acquisition and analysis were performed on a computer with an AD converter and software (LabVIEW, National Instruments, Austin, TX) as previously published. 2.6. Neurobehavioral assessment All animals were videotaped at the same time daily, and a neuroscientist, blinded to the intraoperative course of events, carried out neurological scoring using a modified Tarlov score. The scale is as follows: no voluntary movements (0); perceptible movements at joints (1); good movements at joints but inability to stand (2); ability to get up and stand with assistance 1 min (6); ability to walk 1 min (8); complete recovery (9).
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statistical analysis was performed. The few comparisons cited and p-values given were obtained by Student’s t-tests.
3. Results 3.1. Interpretation Since the major interest in this study was to identify physiological variables which are associated with a poor functional outcome, the animals were divided into two groups depending upon their functional recovery postoperatively. Those animals who regained more or less normal function within the 5 days of observation postoperatively — modified Tarlov score 4 (able to stand without assistance) — were considered to have recovered function. Those pigs with a score
