Assessment and Management of Neurologic Complications After Cardiac and Aortic Surgery

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1 Assessment and Management of Neurologic Complications After Cardiac and Aortic Surgery Joseph S. Coselli, M.D. Professor and Cullen Foundation Endowed Chair Division of Cardiothoracic Surgery Baylor College of Medicine Toronto, Canada Sunday, May 2, 2010

2 Presenter Disclosure Joseph S. Coselli, MD The following relationships exist related to this presentation: Cook, Inc. (PI: TX2 Thoracic Stent Graft Trial) Medtronic, Inc. (PI: Valor II and THRIVE Stent Graft Trial, Consultant, Speaker 2009) WL Gore & Associates, Inc (PI: Gore Conformable Descending/Dissection Thoracic Stent Graft Trial, Speaker , Consultant ) Vascutek Terumo (Educational Grant, Royalties for Coselli Branched Graft for TAAA repairs, and Consultant )

3 Neurologic Injury Injury Following Cardiac or Aortic Surgery Altered Brain Perfusion Inflammatory Response Dispersed Emboli Hypoperfusion Non-pulsatile Perfusion Organ Specific Diffuse Systemic Atherosclerotic Particulate Lipid Gaseous

4 Neurologic Complications Neurologic complications tend to be associated with specific regions of repair Stroke Heart Ascending aorta Aortic arch Paraplegia Descending thoracic aorta Thoracoabdominal aorta

5 Risk Factors: Diabetes & Atherosclerosis 464 consecutive patients ( ) 372 ascending repair 92 arch repair Examined role of diabetes, atherosclerosis, dissection, coronary artery disease, gender, on poor outcomes Hagl JTCVS 2003;126;1005

6 Risk Factors: Diabetes & Atherosclerosis Ascending Aorta Factor P value Odds Ratio Diabetes Atherosclerosis Dissection Multivariate analysis of 372 ascending patients Diabetes, atherosclerosis, and dissection found to be significant predictors of adverse outcomes Death or stroke Hagl JTCVS 2003;126;1005

7 Risk Factors: Diabetes & Atherosclerosis Aortic Arch Multivariate analysis of Factor P value Odds Ratio Female gender Coronary artery disease + Total cerebral protection time 40 min min > 80 min per minute 92 aortic arch patients Female gender, CAD, and increasing total cerebral protection time found to be significant predictors of adverse outcomes Death or stroke Hagl JTCVS 2003;126;1005

8 Predictors of Outcome Univariate analysis of 531 patients 431 with total arch repair Stroke 2.9% 3.3% total arch repair Transient neurocognitive dysfunction 9.9% Ogino JTCVS 2008;136:641

9 Predictors of Outcome Arch vessel malperfusion (in dissection) Aortic arch atheroma Chronic renal failure Odds Ratio Ogino JTCVS 2008;136:641 P-value < Female gender Identified risks for permanent stroke include female gender, chronic renal failure, malperfusion of arch vessels during dissection, and pressence of aortic arch atheroma

10 Effect of prior brain injury on postoperative neurologic outcome Total Arch Replacement 131 patients 10/131 stroke 30/131 transient neurologic dysfunction Preoperative leukoaraiosis and hippocampal atrophy was assessed Morimoto ATS 2009;136:641

11 Predictors of Outcome A) Mild Leukoaraiosis B) Severe Leukoaraiosis C) Hippocampal atrophy was from coronal views of T1 weighted images Morimoto ATS 2009;136:641

12 Predictors of Outcome Stroke OR P-value Arch atheroma Leukoaraiosis score TND OR P-value Aortic atheroma Hippocampal atrophy score Morimoto ATS 2009;136: Leukoaraiosis score 1.3 <0.001 Effect of prior brain injury on postoperative neurologic outcome 131 patients 10/131 stroke 30/131 transient neurologic dysfunction Preoperative leukoaraiosis and hippocampal atrophy was found predictive

13 Early Aortic Arch Replacement Grafts Interesting approaches towards maintaining perfusion Synthetic grafts allow for creative placement DeBakey et al AMA Arch Surg 1958

14 Propose several perfusion strategies based on location Early Aortic Arch Replacement Grafts In their 1962 summary article, the key problems to replacing the aortic arch are Left ventricular strain Ischemic damage Hypothermia has been abandoned in favor of temporary bypass from CPB DeBakey et al SCNA 1962

15 Cardiopulmonary Bypass Associated with inflammatory response Contact of blood with artificial bypass surfaces Conversion of blood to nonpulsatile flow Activation of leukocyte and endothelial cells following ischemic and reperfusion states Activation of complement, fibrinolytic, and cytokine cascades

16 CPB: Complement Cascade Starts when blood contacts the artificial surfaces of the bypass circuit Inflammation increased cytokines Activation leukocytes Microvascular occlusion as leukocytes and endothelial cells interact Results in distal, end-organ ischemia

17 Therapeutic strategies Mitigate CPB-induced Inflammation Corticosteroids: decrease complement activation But, may increase risk of postoperative infection and delay wound healing Aprotinin: inhibits serine protease Withdrawn from market May 2008 due to concerns of increased adverse events

18 138 patients Early Aortic Arch Replacement Grafts Mortality of repair is improving, but remains nearly 20% Increases greatly with age Over age 60 has at least a 40% mortality rate DeBakey et al SCNA, 1962

19 Improving Arch Repair Single anastomosis approach to simplify and expedite repair Techniques to improve cerebral perfusion Assessing adequacy of perfusion extremely difficult Bloodwell et al Ann Thorac Surg 1968

20 Bloodwell et al Ann Thorac Surg 1968

21 1 st Island Arch Repair Bloodwell et al ATS 1968

22 Options During Circulatory Arrest How should we protect the brain? Hypothermic circulatory arrest alone Retrograde cerebral perfusion Antegrade cerebral perfusion

23 Improving Arch Repair Griepp et al J Thorac Cardiovasc Surg 1975 Hypothermia is revisited Benefits of profound hypothermic circulatory arrest for arch repair established Did not use cerebral perfusion 4 patients 3 survivors Limits of perfusion time not yet understood 60 minutes?

24 Impact of Temperature on Brain Normothermia Irreversible brain damage after 4 minutes of arrest Dissolved oxygen plays a trivial role in cerebral oxygen delivery and metabolism 1-2% of arterial O 2 content Profound hypothermia Hb avidity for O 2 / O 2 solubility Decrease CMRO 2 by 65-87% at 18 C Q 10 average 2-3 on CPB Potential safe arrest period Dexter ATS 1997;63:1725 Greeley JTCVS 1991

25 O2 Extraction ml/dl Oxygen Debt After HCA 1.6 Transcranial O 2 Extraction P <0.001 Arrest leads to a progressive O 2 debt manifest as increased oxygen extraction at the end of HCA. The debt is proportional to the duration of arrest 0 Pre HCA Post HCA Bonser JTCVS 2002;123:943

26 Hypothermic Circulatory Arrest HCA without adjuncts remains an acceptable approach, but has clear limitations. Stroke 7% Mortality 10% HCA used during aortic surgery in 656 patients 40 min increased stroke rate 65 min increased mortality rate Svensson et al J Thorac Cardiovasc Surg 1993

27 Improving Arch Repair Ueda Retrograde Perfusion Nippon Kyobu Geka Gakki Zasshi 1988 [Surgical treatment of the aneurysm or dissection involving the ascending aorta and aortic arch using circulatory arrest and retrograde perfusion] Article in Japanese Introduces concept of retrograde cerebral perfusion in 1988 Presents experience in 249 patients in patients with aneurysm 116 patients with dissection Average duration of RCP was 46 min Overall mortality was 24/249 (10%) Ueda et al Ann Thorac Surg 1999

28 Retrograde Cerebral Perfusion Potential benefits Cerebral metabolic support Maintenance of intracranial hypothermia Flushing of embolic debris and waste metabolites

29 Liver Spleen Kidney Heart Cortical grey Cortical white Hippocampus Cerebellum Medulla oblongata Regional organ blood flow (ml/min/100g) at 18 o C Minimal cerebral blood flow during retrograde cerebral perfusion (Microsphere CBF measurement technique) Antegrade cerebral perfusion Retrograde cerebral perfusion hour HCA / RCP Boeckxstaens et al. Ann Thorac Surg 1995;60:

30 Incidence of neuropsychometric deficit in HCA and HCA + RCP groups 100 p=0.22 % Neuropsychometric deficit p= weeks 12 weeks HCA RCP Harrington et al, J Thorac & Cardiovasc Surg, 2003

31 Mortality and stroke rate HCA ± RCP (479 pts) % event day mortality In-hospital deaths Stroke P< P< P< All patients(n=479) HCA + RCP (n=290) HCA only (n=189) * But HCA Only group had greater incidence of DM, CVA and Aortic dissection p<0.025 Coselli J Card Surg 1997;12(suppl):

32 Retrograde Cerebral Perfusion Widely used in recent past Developing consensus that efficacy is limited Failure to provide metabolic support Use is declining

33 Improving Arch Repair Return to Antegrade Cerebral Perfusion Flexible catheters facilitate use Kazui Antegrade Perfusion Annals of Thoracic Surgery 1992 Selective cerebral perfusion during operation for aneurysm of the aortic arch: a reassessment.

34 Antegrade Cerebral Perfusion Clear potential advantages Popularity of axillary artery cannulation increasing use

35 Improving Arch Repair Cerebral perfusion is revisited 10 patients spanning 1970 to 1985 Simplified CPB with partial brachiocephalic perfusion Moderate cooling Frist et al Ann Thorac Surg 1986

36 Intra-operative Management Use of transcranial Doppler to monitor cerebral perfusion Aortic Arch Surgery: Edmonds Ch

37 Intra-operative Management Use of near infrared spectroscopy to monitor cerebral perfusion

38 Perfusion via Axillary Artery Cannulation Rationale Simplifies delivery of antegrade cerebral perfusion Avoids malperfusion ACP via axillary artery has emerged as the method of choice.

39 Perfusion via Axillary Artery Cannulation

40 Axillary Cannulation 869 patients with ascending aorta/root repairs From 1995 to 2005 Right axillary cannulation in 451 patients Atherosclerotic aneurysm in 122 patients Cannulation n Death Stroke Axillary 66 2 (3%) 0 Femoral 26 2 (8%) 2 (8%) Ascending 30 3 (10%) 4 (13%) All (6%) 6 (5%) Axillary cannulation was associated with a significantly better outcome (p = 0.05) Etz et al, Ann Thorac Surg 2008

41 Axillary Cannulation 1352 patients repairs with circulatory arrest 415 arch repairs From 1993 to 2003 Axillary or subclavian cannulation plus graft 299 Axillary or subclavian without graft 167 Propensity matched Cannulation n Death Stroke Axillary plus graft (7%) 12 (4%) Direct (9%) 69 (7%) All (8%) 81 (6%) Axillary cannulation was associated with a significantly better outcome (p = 0.09 and p = 0.05 in matched pairs) Svensson et al, Ann Thorac Surg 2004

42 Improving Arch Repair Total Experience As hypothermic circulatory arrest time increases, mortality and stroke increase Experience in 347 arch repairs ( ) Sundt et al Ann Thorac Surg 2008

43 Improving Arch Repair Retrograde CP Antegrade CP Appears to neutralize extended operative times Sundt et al Ann Thorac Surg 2008

44 IRAD Mortality: Acute Type A Dissection Analysis stratified by age Although younger surical patients did better (P=.005), all surgical patients did much better than medical only <70 yrs 21% early death >70 yrs 31% early death Management Total n (All Ages) Mortality n (%) Medical /153 (59%) Surgical /769 (24%) Trimarchi IRAD JTCVS In Press 2010

45 Axillary Artery Cannulation in Surgery For Acute or Subacute Ascending Aortic Dissections Wong, Coselli, Palmero, Bozinovski, Carter, Murariu, LeMaire Purpose: To describe the short- and mid-term results for repair of acute and subacute ascending aortic dissections in patients Dec 2003 April 2007 Wong, Coselli et al Ann Thorac Surg In Press 2010

46 Patients Baseline Patient Characteristics (n = 83) Age (years) 58 (22-84) Previous dissection 10 (12%) Previous stroke 7 (8%) Previous MI 6 (7%) COPD 9 (11%) Renal insufficiency/failure 3 (4%) Visceral ischemia 2 (2%) Wong, Coselli et al Ann Thorac Surg In Press 2010

47 Patients Presenting Disease Characteristics (n = 83) Disease Type Classic dissection 81 (98%) Intramural hematoma 2 (2%) Acuity of Dissection Acute 75 (90%) Subacute (15-60d) 8 (10%) Diseased Aortic Segment Ascending + desc aorta (DeBakey type I) 65 (78%) Ascending aorta only (DeBakey type II) 18 (22%) Wong, Coselli et al Ann Thorac Surg In Press 2010

48 Patients Findings at Presentation (n = 83) Rupture 7 (8%) Pericardial effusion 24 (29%) Cardiac tamponade 4 (5%) Acute neurologic injury Stroke 2 (2%) Transient ischemic attack 3 (4%) Paraplegia/paraparesis 2 (2%) Other 11 (13%) Wong, Coselli et al Ann Thorac Surg In Press 2010

49 Surgical Technique Operative Details (n = 83) Aortic valve replacement 4 (5%) Root replacement 16 (19%) Aortic valve repair 47 (57%) Hemiarch replacement 77 (93%) Elephant trunk arch replacement 3 (4%) Coronary artery bypass 13 (16%) Redo sternotomy 16 (19%) Wong, Coselli et al Ann Thorac Surg In Press 2010

50 Surgical Technique Operative Details (n = 83) CPB time, min 138 Cross-clamp time, min 57 Circulatory arrest time, min 37 Unprotected ischemic time, min 9 Wong, Coselli et al Ann Thorac Surg In Press 2010

51 Results Short-Term Outcomes (n = 83) Death, in-hospital or within 30 days 14 (17%) Stroke (6 with full recovery) 9 (11%) Paraplegia/paraparesis 0 Myocardial infarction 0 Reoperation for bleeding 7 (8%) Wong, Coselli et al Ann Thorac Surg In Press 2010

52 Survival (%) Results 3 Year Actuarial Survival: 63.5 ± 6% Mean follow-up time: 1.6 ± 1.3 yrs Time (years) Wong, Coselli et al Ann Thorac Surg In Press 2010

53 Mortality Acute Type A Dissection Author Year n Mortality Trimarchi IRAD in press (24%) Tsai IRAD (27%) Raghupathy IRAD (23%) Narayan (18%) Knipp NIS (26%) Erwin (23%) Haverich (24%)

54 Trifurcated Graft Technique 2002 Ann Thorac Surg 2002;74:S1810-4

55 Trifurcated Graft Technique patients over 6 years ( ) Adverse outcomes in 13 (8.7%); 7 hospital deaths (4.7%); 6 permanent strokes (4.1%) 7 patients (4.7%) with temporary neurological dysfunction 9 patients (6.0%) required dialysis for transient renal failure ICU LOS: 3 (1-108) days; Total LOS: 10 (4-108) days Use of technique with HCA and SCP is safe and versatile Ann Thorac Surg 2007;83:S791-5

56 Traditional Partial Arch Group n=165 (68%) 243 Arch Repairs : % Hemi-arch (n=157) Partial Arch with Innominate Graft (n=7)... Patch Repair (n=1)

57 Traditional Total Arch Group n=23 (10%) 243 Arch Repairs: % Arch with Island (n=3). Arch with Branched Arch Graft (n=6) ET with Island (n=14)

58 Trifurcated Graft Group n=55 (23%) 243 Arch Repairs: % Arch with Bifurcated Graft (n=7) Arch with Trifurcated Graft (n=1) ET with Bifurcated Graft (n=40) ET with Trifurcated Graft (n=7)

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69 Operative Variables Operative Variables for 55 Patients Who Underwent Total Aortic Arch Replacement using the Trifurcated Graft Technique Urgency of Operation: Elective 43 (78%) Urgent 10 (18%) Emergent 2 (4%) Repeat Sternotomy 33 (60%) Concomitant procedures: Aortic valve replacement 12 (22%) Aortic valve repair (commissural plication) 10 (18%) Aortic root replacement 5 (9%)

70 Early Outcomes Early Outcome Characteristics of 55 Patients Who Underwent Total Aortic Arch Replacement using the Trifurcated Graft Technique Operative death: Hospital 0 (0%) Operative death: 30-day 1 (2%)* Bleeding requiring reoperation 4 (7%) Stroke 3 (5%) Myocardial Infarction 1 (2%) Arrhythmia 22 (40%) Atrial arrhythmia 21 (38%) Ventricular arrhythmia 3 (5%) *Pericardial effusion presenting with tamponade 13 days after discharge (21 days postop)

71 46 patients (98%) survived Stage I elephant trunk procedure 30 patients (65%) returned for Stage II Results, Late Outcomes Operative mortality for Stage II was 4% (1 patient) Open Stage II Repair 25/30 (83%) Endovascular Stage II Repair 5/30 (17%)

72 Comparison Outcome Variables Trifurcated Graft Technique (n=55) Traditional Partial Arch Replacement (n=165) Operative death 1 (2%) 10 (6%) 1 (4%) Stroke 3 (5%) 7 (4%) 3 (13%) Renal failure dialysis 3 (5%) 4 (2%) 1 (4%) Reoperation for bleeding 4 (7%) 9 (6%) 3 (13%) Traditional Full Arch Replacement (n=23) Actuarial 1-year survival % % % * p < 0.05 vs. Trifurcated Graft Technique group

73 Can we use Higher Temperatures? Hypothermic Circulatory Arrest: Group 1: Temperature < 20 ºC (16.7±1.7 ºC ) Group 2: Temperature 20 ºC (22.9±1.4 ºC ) Coselli, unpublished data 2010

74 Preoperative Characteristics Group 1 (n = 99) % Group 2 (n = 142) % P Value (χ 2 ) Female gender 34% 32% Age in years 62 ± ± Diabetes mellitus 9% 6% Smoking history 31% 41% Renal insufficiency 14% 14% Hypertension 85% 87% Carotid artery disease 13% 12% Pulmonary disease 24% 38% Coronary artery disease 30% 37% Congestive heart failure 35% 51% NYHA class III or IV 38% 41% History of CVA 7% 12% Acute aortic dissection 15% 13% Coselli, unpublished data 2010

75 Preoperative and Operative Characteristics Medical therapy Group 1 (n = 99) % Group 2 (n = 142) % P Value (χ 2 ) Use of antiplatelet agent 36% 39% Use of β-blocker 66% 70% Use of calcium channel blocker 23% 26% Use of statins 35% 40% Operative characteristics Hemi or partial arch surgery 74% 63% Total arch surgery 26% 37% Emergent surgery 17% 13% Reoperation, prior sternotomy 32% 36% Mean duration HCA, minutes 38 ± ± Mean duration CPB, minutes 154 ± ± Coselli, unpublished data 2010

76 Perioperative Transfusion Group 1 (n = 99) Group 2 (n = 142) P Value (χ 2 ) PRBC units FFP units Platelet aphresis units Coselli, unpublished data 2010

77 Postoperative Outcomes Group 1 (n = 99) % Group 2 (n = 142) % P Value (χ 2 ) Odds Ratio 95% Confidence Intervals 30-day mortality 9.1% 2.1% Hospital death 8.1% 0.7% Stroke 9.1% 2.8% Tracheostomy 23% 23% NS Postoperative RI 1.7% 2.2% NS Postoperative myocardial infarction 2.0% 1.4% NS Atrial fibrillation 36.4% 31.7% NS Sepsis 3.0% 3.3% NS Postoperative dialysis Hospital length of stay, days 5.1% 2.1% NS 18 ± ± Coselli, unpublished data 2010

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79 Hybrid Approaches Gore TAG endograft 28x10cm distally. Placement of a 34x10 cm Gore TAG endostent proximally to the ascending aorta

80 Hybrid Approaches

81 STROKE RISK

82 Paraplegia Distal perfusion Shunts LHB CPB CPB + HCA Pharmacology Steroids Naloxone No Morphine Hypothermia Regional CPB Intercostal arteries Direct reattachment Preconditioning

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86 # of Patients Left Heart Bypass v. No Bypass Paraplegia/Paraparesis in 751 Extent II TAAA % 10.2% Total Patients PAR/PLG p = Left Heart Bypass No Bypass Coselli

87 Cerebrospinal Fluid Drainage CSF pressure s during aortic clamping Blaisdell & Cooley, 1962 Ligation/Pressure studies At least 2 arteries needed Spinal perfusion MAP CSF pressure Goal improve spinal perfusion pressure Widespread use now commonly applied to endovascular approaches DTA/TAAA

88 Incidence of Paraplegia (%) 156 Extent I/II TAAA Repairs: With vs. Without CSF Drainage 20 P = With CSFD Without CSFD Coselli et al J Vasc Surg 2002

89 Hypothermic Circulatory Arrest Approaches to TAA Aneurysm Repair Profound Hypothermic Circulatory Arrest Standard use of HCA in TAAA repairs Kouchoukos Ann Thorac Surg 2001 Kouchoukos Ann Thorac Surg 2002 Fehrenbacher Ann Thorac Surg 2007 Aortic Symposium 2010 (C I II III) 218 patients Mortality 7.3% Paraplegia 4.6% Renal Failure - dialysis 6.9%

90 Hybrid Thoracoabdominal Repairs Comparison of Results Hybrid Open No. of Operative Renal Early Patients Mortality Paraplegia Dysfunction Endoleaks (16.7%) 10 (4.5%) 28 (12.6%) 51 (23.0%) [10-33] [0-31%] [0-15%] [0-29%] [0-62%] 5, (7.1%) 280 (5.2%) 276/4210 (6.6%) 0 [ ] [5-17%] [2-9%] [2-12%] P < P = Black 2006 Chiesa 2007 Siegenthaler 2008 Muehling 2009 Resch 2006 Lee 2007 Aguiar Luis 2009 Patel 2009 Zhou 2006 Böckler 2008 Kabanni 2009 Quinones-Baldrich 2009 Kouchoukos 2001 Jacobs 2006 Etz 2008 Schepens 2009 Chiesa 2004 Conrad 2007 Misfeld 2008 Sandmann 2005 Coselli 2007 Patel 2009

91 Early Outcomes in 441 TAAA Patients by Crawford Extent of Repair Crawford Extent of Repair Factor Extent I Extent II Extent III Extent IV (n = 111) (n =138) (n = 84) (n = 108) Early death In-hospital or 30-day death 4 (4%) 9 (7%) 6 (7%) 7 (6%) Permanent paraplegia 1 (1%) 5 (4%) 3 (4%) 1 (1%) Overall rate of permanent paraplegia is 2.3% (10/441) Mesenteric ischemia 0 1 ( 1%) 0 1 (1%) Acute renal dysfunction 11 (10%) 20 (14%) 11 (13%) 13 (12%) Acute renal failure 9 (8%) 14 (10%) 7 (8%) 9 (8%) On dialysis at discharge 2 (2%) 7 (5%) 3 (4%) 8 (7%) Overall rate of permanent renal failure is 4.5% (20/441) Unpublished Coselli Data March 2010

92 Paraplegia in 409 Patients by Crawford Extent of Repair Crawford Extent of Repair Factor Extent I Extent II Extent III Extent IV (n = 102) (n = 126) (n = 79) (n = 102) Paraplegia 7 (7%) 9 (7%) 5 (6%) 2 (2%) Immediate 0 2 (22%) 1(20%) 0 Delayed 7 (100%) 7 (78%) 4 (80%) 2 (100%) At discharge 1 (1%) 5 (4%) 3 (4%) 1(1%) Immediate 0 1 (20%) 1 (33%) 0 Delayed 1 (100%) 4 (80%) 2 (67%) 1 (100%) Most patients with paraplegia had delayed deficits

93 Paraplegia Rescue CSF Pressure 6 10 mmhg Steroids Mannitol Increase Systolic BP Maximize Oxygenation Optimize Hemodnamics and CO Naloxzone

94 Conclusions Early results using trifurcated graft technique compare favorably to traditional approaches Enables effective delivery of SCP Minimizes unprotected cerebral ischemic time Associated with low risk of neurological sequelae Readily adapted to accommodate anatomic variations Possibly reduce temp and operative time

95 Cannulation and Cooling Cannulation Axillary artery Temperature gradient 7 C Perfusion flow L.min-1min-2 Cooling duration minutes Nasopharyngeal temperature 24 C for >5 minutes Jugular bulb O2 saturation 95% Pre-treatment Mannitol 1g.kg-1 Dexamethasone 12mg 20 min pre-arrest Hematocrit 20-30% ph management alpha-stat Glucose management Insulin sliding scale WBG <10mmol.L-1

96 Arrest Period and ACP Position Trendelenberg 15 o C Technique HCA alone for anticipated arrest times 20 minutes ACP for all other cases Cannulation Balloon perfusion catheter via left carotid artery Left subclavian artery Occlusion with embolectomy catheter Perfusate temperature 15 C Hematocrit 20-30% Flow rate ml.kg-1.min-1 LCCA perfusion pressure mmhg without overt manipulation

97 Reperfusion and Rewarming Air Meticulous arch airdrill Perfusion flow L.min -1 min -2 Reperfusion temperature 24 o C for 5 minutes Temperature gradient 7 o C Nasopharyngeal temperature maximum 36.5 o C Arterial outflow temperature maximum 37 o C Rewarming duration Nasopharyngeal temperature 36.5 o C minutes Hematocrit 20-30% ph management alpha-stat Glucose management Insulin sliding scale WBG <10mmol.L -1

98 Thank you!