Accepted Manuscript Complete Resolution of Post-Operative Hemiparesis following Carotid Endarterectomy with Therapeutic Hypothermia: A case study and literature review Irina Usach, MHS, Andreas Sakopoulos, MD FACS, Hossein Razavi, MD FACP FCCP PII: S0890-5096(15)00404-5 DOI: 10.1016/j.avsg.2015.03.048 Reference: AVSG 2388 To appear in: Annals of Vascular Surgery Received Date: 20 November 2014 Revised Date: 20 February 2015 Accepted Date: 2 March 2015 Please cite this article as: Usach I, Sakopoulos A, Razavi H, Complete Resolution of Post-Operative Hemiparesis following Carotid Endarterectomy with Therapeutic Hypothermia: A case study and literature review, Annals of Vascular Surgery (2015), doi: 10.1016/j.avsg.2015.03.048. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. 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ACCEPTED MANUSCRIPT 3 4 5 6 7 RI PT 2 Complete Resolution of Post-Operative Hemiparesis following Carotid Endarterectomy with Therapeutic Hypothermia: A case study and literature review Irina Usach, MHS1; Andreas Sakopoulos, MD FACS1; Hossein Razavi, MD FACP FCCP2 8 9 10 11 12 13 14 15 16 1 17 18 19 20 21 22 23 24 Please address correspondence to: Andreas Sakopoulos, MD FACS Cardiothoracic and Endovascular Surgery St. Helena Hospital 10 Woodland Road, St. Helena, CA 94574 Email: andreas.sakopoulos@ah.org Phone number: 707-963-6315 Cardiothoracic and Endovascular Surgery St. Helena Hospital, St. Helena, CA 10 Woodland Road, St. Helena, CA 94574 2 AC C EP TE D M AN U Pulmonary and Critical Care Medicine St. Helena Hospital, St. Helena, CA 10 Woodland Road, St. Helena, CA 94574 SC 1 1 ACCEPTED MANUSCRIPT ABSTRACT 2 Therapeutic hypothermia (TH) is indicated in a number of traumatic brain injuries as well 3 as for cardiovascular shock1, but it has been limited in its application to acute ischemic 4 stroke. We present the case of a 65-year-old woman with a clinical cerebrovascular 5 accident (CVA) following a right carotid endarterectomy who was treated with a 24-hour 6 hypothermia protocol and had a full recovery. The hypothermia protocol utilized on this 7 patient and a review of the literature surrounding hypothermia in the setting of ischemic 8 stroke are presented. SC RI PT 1 10 M AN U 9 INTRODUCTION TH has been utilized in the treatment of traumatic brain injury and cardiogenic 12 shock, showing decreased cerebral and myocardial damage, improved post-ischemic 13 cardiac function and reduced end-organ damage due to hypoperfusion1,2. Specifically, in 14 cardiogenic shock patients it has been shown that lowering brain temperature, even if 15 only by a few degrees, reduces ischemic damage2,3. However, despite the underlying 16 similarities in the pathophysiology of injury, the benefits of TH have not been fully 17 explored in patients with acute ischemic stroke. EP TE D 11 We present one case of acute ischemic stroke following right carotid 19 endarterectomy (CEA) that was treated with immediate TH, lasting 24 hours. 20 21 AC C 18 CASE REPORT 22 A 65-year-old woman with no prior history of CVA presented to clinic with 23 carotid duplex ultrasound findings of greater than 70% stenosis of her right internal 24 carotid artery. The patient underwent a standard right CEA with the use of a shunt with 2 ACCEPTED MANUSCRIPT Doppler, which demonstrated sustained blood flow throughout the procedure. The CEA 2 was completed with no apparent intraoperative complications. During awakening from 3 anesthesia and prior to extubation, the patient showed flaccid paralysis of the left upper 4 and lower extremities. This left-sided hemiparesis was clinically suggestive of an acute 5 CVA. Upon re-exploration, surface Doppler ultrasound demonstrated signal on the right 6 internal, external and common carotid arteries. The artery was opened and an 7 embolectomy catheter was advanced and pulled back, with no return of debris. Upon 8 closing, the patient was taken to radiology for an emergency computed tomography (CT) 9 as well as a computed tomographic angiography (CTA). The CT and CTA were both 10 unremarkable, showing no signs of hemorrhagic stroke and confirming presence of patent 11 cerebral vasculature throughout the right and left hemispheres (Figure I). However, these 12 findings did not rule out the possibility of ischemic stroke, and given the clinical severity 13 of the patient’s symptoms, it was clear that the patient had suffered an ischemic stroke. 14 At this time, tissue plasminogen activator (tPA), the standard protocol for an ischemic 15 stroke within 4 hours of symptomatic onset, was contraindicated due to recent surgery. 16 The patient was then taken to the intensive care unit where a standard 17 hypothermic protocol was initiated. The patient was sedated with propofol, given 18 vecuronium as a paralytic, and cooled with IV saline and cooling blankets to 33°C, 19 maintaining that temperature for 24 hours. At that time, the patient was rewarmed, 20 extubated and a full neurological exam was performed. The patient was able to follow 21 commands; Cranial Nerves I-XII were intact to motion and sensory; strength was 5/5, 22 bilaterally in upper and lower extremities; deep tendon reflexes were +2/4, bilaterally in 23 upper and lower extremities; sensation to pain, vibration, light and deep touch were AC C EP TE D M AN U SC RI PT 1 3 ACCEPTED MANUSCRIPT 1 intact, bilaterally in upper and lower extremities. The patient showed no signs of focal 2 neurological deficit and was discharged on post-operative day 4. 3 DISCUSSION RI PT 4 Despite evidence of the neuroprotection of TH in ischemic brain injury and 6 cardiopulmonary resuscitation, there has been very little data showing the benefit of TH 7 in acute ischemic stroke patients. In this case report we describe the presumed benefit of 8 TH in a patient who suffered an acute CVA immediately post-operatively and benefited 9 from this therapy. Although we cannot be certain that there is a true causal relationship 10 between TH and the resolution of our patient’s hemiplegia, there is clearly a temporal 11 relationship. There is compelling evidence to support our theory that cooling neuronal 12 cells may ameliorate damage caused by ischemia and/or trauma. M AN U In 2014, Xu et al. presented compelling data that demonstrated the TE D 13 SC 5 neuroprotective nature of TH in rat models that were exposed to global ischemia using an 15 in vitro model of oxygen glucose deprivation4. Xu et al. found that intermittent 16 hypothermia offered protection against ischemic injury on a cellular level altering 17 viability and inhibiting cellular death pathways4. That same year, Matsui et al. found that 18 hypothermia significantly decreases the release of Interleukin 17 and Granzyme B, 19 factors that mediate neuronal cell death, from T-cells following a model for toxic 20 neuronal cell injury (P < 0.05 when compared with normothermia)5. This finding 21 suggests that hypothermia plays an important role in neuroprotection as the immune 22 system recognizes, and responds to, acute brain injury. AC C EP 14 4 ACCEPTED MANUSCRIPT In January 2015, Alonso-Alconada et al. used a piglet asphyxia model to prove 2 that cooling the brain to 33.5-35°C was protective in brain regions following ischemic 3 injury in an animal model6. Time has also been shown to be an important factor in the 4 effectiveness of TH. Yenari and Hemmen found that TH is most neuroprotective when it 5 is applied during, or even before, the onset of ischemia7. This is both applicable and 6 supportive of the application of immediate TH in the setting of CVA following CEA. Despite the benefits of neuronal protection, TH does have potential adverse SC 7 RI PT 1 effects to be aware of. It has been shown to provoke pneumonia8, coronary spasm and 9 life-threatening arrhythmias3 and should therefore be used with caution in patients with 10 pulmonary and/or cardiac comorbidities. M AN U 8 While this is clearly a single case report, and is limited in the scope of its 12 application, it may still be beneficial to consider a protocol whereby TH could be 13 considered as one of the therapeutic interventions available in the setting of ischemic 14 stroke. Other limitations include a lack of radiographic criteria to make a firm diagnosis 15 of CVA. However, clinically, our patient did have complete hemiparesis, which resolved 16 post-intervention. While, our patient’s hemiparesis may have been transient, the temporal 17 relationship between the symptomatic resolution and TH is definitive enough to warrant 18 further research. Although narrow in its application, the use of TH in acute CVA can be 19 an important and effective therapeutic option immediately following CEA. Further 20 research must be directed at the effectiveness of TH in this setting. EP AC C 21 TE D 11 22 23 5 ACCEPTED MANUSCRIPT 1 Warner, D. S., et al. "Translational Research in Acute Central Nervous System Injury: Lessons Learned and the Future." JAMA Neurol (2014). Stegman, B. M., et al. "Post-Myocardial Infarction Cardiogenic Shock Is a Systemic RI PT 2 Illness in Need of Systemic Treatment: Is Therapeutic Hypothermia One Possibility?" J Am Coll Cardiol 59.7 (2012): 644-7. Todaro, M. C., et al. "Hypothermia: A Double-Edged Sword." Cardiology 122.2 (2012): SC 3 126-8. Xu, S. Y., et al. "Intermittent Hypothermia Is Neuroprotective in an in Vitro Model of M AN U 4 Ischemic Stroke." Int J Biol Sci 10.8 (2014): 873-81. 5 Matsui, T., et al. "Hypothermia Reduces but Hyperthermia Augments T Cell-Derived Release of Interleukin-17 and Granzyme B That Mediate Neuronal Cell Death." Neurocrit Care (2014). Alonso-Alconada, D., et al. "Brain Cell Death Is Reduced with Cooling by 3.5 Degrees TE D 6 C to 5 Degrees C but Increased with Cooling by 8.5 Degrees C in a Piglet Asphyxia 7 EP Model." Stroke 46.1 (2015): 275-8. Yenari, M. A., and T. M. Hemmen. "Therapeutic Hypothermia for Brain Ischemia: 8 AC C Where Have We Come and Where Do We Go?" Stroke 41.10 Suppl (2010): S72-4. Nolan, J. P., et al. "Therapeutic Hypothermia after Cardiac Arrest. An Advisory Statement by the Advancement Life Support Task Force of the International Liaison Committee on Resuscitation." Resuscitation 57.3 (2003): 231-5. 6 ACCEPTED MANUSCRIPT FIGURE AC C EP TE D M AN U SC RI PT Figure I: Post-operative CT Angiography: Sagittal section, 9° showing patent right internal carotid