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2. CCS 2016 Guideline: Optimal Care of the Post Arrest Patient

3. INTRODUCTION

4. Purpose: To provide a practical yet comprehensive approach to survivors of cardiac arrest for a Canadian setting Emphasize the concept of a “Care bundle” encompassing 4 key aspects of care for the post arrest patient: 1. Targeted temperature management (TTM) 2. Coronary angiography and revascularization 3. Critical care management 4. Regionalization of post-arrest care Topics NOT covered: Mechanical cardiac support Neuroprognostication/end of life decision making Overview of the 2016 Update

5. Primary Author PanelCCU Directors Working Group, CAIC, CANCARE Graham Wong MD MPH (Co-Chair) Michel Le May MD (Co-Chair) Craig Ainsworth MD Rakesh Arora MD Jean Diodati MD Mark Liszkowski MD Michael Love MD Chris Overgaard MD Greg Schnell MD Jean François Tanguay MD Sean Van Diepen MD George Wells PhD University of British Columbia University of Ottawa McMaster University University of Manitoba Université de Montréal Université de Montréal Dalhousie University University of Toronto University of Calgary Université de Montréal University of Alberta University of Ottawa

6. Methodology Developed in accordance with the CCS “Framework for Application of GRADE in CCS Guideline and Position Statement Development”http://www.ccs.ca/images/Guidelines/Dev_process/CCS_GRADE_Framework_June2015.pdf The Primary Panel developed a set of clinical questions in PICO (Population, Intervention, Comparison and Outcome) format for each subtopic in addition to statements of Values and Preferences Literature searches conducted using PubMed, Embase, and The Cochrane Library with the help of a medical librarian Studies identified were evaluated for quality and bias using GRADE methodology Recommendations were made by majority (>75%)votes of all authors based upon the quality of the available evidence in addition to the Values and Preferences for each section

7. Practical Use of Targeted Temperature Management

8. Practical Use of Targeted Temperature Management We define TTM as a strategy of intentional temperature management of a post-arrest patient comprising active patient cooling, subsequent rewarming, and extended fever control We define “comatose” or “unresponsiveness” in post-arrest patients as an absence of purposeful response to verbal commands

9. OHCA with an Initial Shockable Rhythm Which Patient Populations Benefit from TTM?

10. Which Patient Populations Benefit from TTM? Resuscitation. 2015;95:202-22 Circulation. 2015;132[suppl 1]:S84-S145

11. Too few patients studied (total n = 350 patients) HACA n = 273 Bernard n = 77 Large difference in intensive care compared with today HACA: 20% received thrombolysis Bernard: 3 patients received thrombolysis; 3 patients underwent angioplasty High risk of bias No standardized protocol for withdrawal of care Concerns about the 2002 Trials

12. Fever in the control group Concerns about the 2002 Trials HACA. N Engl J Med 2002;346:549-56.

13. Recommendation: We recommendthat TTM be used in unresponsive OHCA survivors with an initial shockable rhythm following return of spontaneous circulation (ROSC) (Strong Recommendation, Low Quality Evidence). Values and Preferences: Despite the overall low quality of evidence we considered the low NNT, ease of administration and low cost of TTM for this strong recommendation. Recommendation

14. 2. OHCA with an Initial Non - Shockable Rhythm 3. IHCA with any Initial Rhythm Which Patient Populations Benefit from TTM?

15. Recommendation:We suggestTTM be used in unresponsive OHCA survivors with an initial non-shockable rhythm following ROSC (Conditional Recommendation, Very Low Quality Evidence). Values and Preferences: Although the evidence base is inconclusive, we valued the potential benefit and apparent lack of harm of TTM in this patient group. Practical Tip:Patients with an initial shockable rhythm have improved rates of survival with a good neurological outcome compared to those with an initial non-shockable rhythm. It is important to carefully consider patient age, comorbidities, and the resuscitation history when determining the subset of patients with non-shockable rhythms who are more likely to benefit from TTM. In the highest quality study, patients who benefited from TTM in this subgroup­­ had age <75, a witnessed arrest, or ROSC <40 min. Recommendation

16. Recommendation: We suggestthat TTM be considered in unresponsive survivors of IHCA with any rhythm following ROSC (Conditional Recommendation, Very Low Quality Evidence). Values and Preferences: As there is no high-quality evidence to support or disprove the use of TTM in this patient population, the potential benefit and lack of harm influenced our recommendation. Recommendation

17. Is There a Preferred Temperature When Using TTM? N = 939 comatose survivors of OHCA Shockable and non-shockable rhythms Primary endpoint was all-cause mortality No difference between 33°C versus 36°C Nielsen, et al. NEJM. 2013;369:2197-206.

18. TTM Trial Pros & Cons • Designed as a superiority trial • Higher bystander CPR rate • Time between ROSC and onset of cooling was delayed • Rate of cooling was not standardized • Rewarming was too rapid • Well controlled temperature targets • Study population more closely resembling clinical practice • “Modern” ICU/CICU care • Predefined protocols for withdrawal of care

19. Recommendation:We recommend that a temperature between 33 and 36°C, inclusively, be selected and maintained for patients undergoing TTM (Strong Recommendation, Moderate Quality Evidence). Values and Preferences: We acknowledge that the evidence does not conclusively favour a temperature of either 33°C or 36°C, so practitioners may use a temperature range. We favoured 33°C rather than 32°C as the lower bound of our recommended temperature range based on the current primary literature. Practical Tip:The chosen target temperature should ideally be maintained during the active temperature management phase. Excessive bradycardia or hemodynamic instability at 33°C may be improved by raising the target temperature to up to 36°C. Recommendation

20. What is the Benefit of Pre-hospital use of TTM? Seven RCTs studied the effect of initiating TTM in the pre-hospital setting on favourable neurologic outcome or survival only at discharge. N = 1359 cooled with chilled IV fluids Did not improve survival or neurological status at hospital discharge Increased hypoxemia and radiographic pulmonary edema in the first 24 hrs JAMA 2014;311:42-52.

21. Recommendation:We do not recommend the use of chilled intravenous fluids for pre-hospital cooling after ROSC (Strong Recommendation, Moderate Quality Evidence). Practical Tip:Given the lack of evidence, the risk vs. benefit of initiating TTM should be individualized when long transport times are anticipated. There is insufficient evidence to provide a recommendation regarding other methods of pre-hospital cooling. Recommendation

22. What is the Optimal Method of Delivering TTM? Recommendation:We suggest that either surface cooling or intravascular cooling techniques may be utilized to induce and maintain TTM. (Conditional Recommendation, Low Quality Evidence). Practical Tip: Both surface and intravascular cooling devices have their own unique advantages and disadvantages. The choice of method should take into account patient variables, equipment availability, and institutional expertise.

23. What is the Optimal Method of Delivering TTM? Recommendation:We suggest that the cooling temperature selected for TTM should be maintained for at least 24 hours. (Conditional Recommendation, Very Low Quality Evidence). Recommendation:We suggest TTM may be continued beyond 24 hours from ROSC to prevent fever (temperature > 37.5°C) (Conditional Recommendation, Very Low Quality Evidence). Values and Preferences: Despite the controversy as to whether the presence of fever is a cause or consequence of cerebral anoxia, we value the potential benefit and low risk of continuing TTM beyond 24 hours for this recommendation.

24. Angiography and Revascularization Following OHCA

25. Introduction • Ischemic heart disease is the most frequent cause of OHCA, with acute coronary occlusion causing pulseless ventricular tachycardia (VT) or ventricular fibrillation (VF) in many cases. • Prompt identification and appropriate management of culprit coronary artery disease (CAD) is therefore important. • Case series demonstrate an association between routine diagnostic coronary angiography and PCI in OHCA survivors with improved survival.

26. The presence of ST-segment elevation in OHCA survivors is associated with underlying culprit CAD. • Comatose OHCA survivors with STEMI have increased long-term mortality relative to other STEMI patients but they do benefit from successful PPCI. • Retrospective data suggests fibrinolysis and PPCI are associated with improved rates of hospital discharge and neurological recovery amongst survivors of OHCA, with a suggestion that PPCI may be superior to fibrinolysis. Role of Coronary Angiography in OHCA Patients with STEMI

27. Recommendations • We recommend that in OHCA patients with STEMI, immediate angiography and PPCI be considered when timely access to cardiac catheterization is feasible. (Strong Recommendation, Moderate Quality of Evidence) • We recommend fibrinolysis for OHCA patients with STEMI if timely PPCI cannot be performed and there are no absolute contraindications to its use. (Strong Recommendation, Low Quality Evidence) • We recommend againstfibrinolysis as an adjunctive resuscitative agent for OHCA patients. (Strong Recommendation, Moderate Quality Evidence)

28. Clinical outcomes after routine angiography in patients without STEMI on presentation are mixed, with some studies demonstrating improved survival with routine angiography, and others demonstrating no benefit. • A strategy of routine angiography for all unselected OHCA survivors has less benefit compared to restricting angiography for selected OHCA patients post-ROSC. Role of Coronary Angiography in OHCA Survivors Without STEMI

29. Recommendation • We suggest urgent angiography ± PCI be performed in patients without ST-elevation following OHCA if there is a high suspicion for ACS and no major comorbidities or contraindications to invasive angiography. (Conditional Recommendation, Moderate Quality Evidence)

30. Practical Tips: • The need for urgent diagnostic coronary angiography +/-PCI in OHCA survivors without STEMI should incorporate the likelihood of benefit from acute coronary revascularization and the perceived risk of the procedure. • Neurologic status should not be regarded as a contraindication to early invasive assessment following OHCA. • No randomized trial has defined the optimal timing for angiography amongst OHCA survivors without STEMI, but we believe it is reasonable to proceed with angiography for OHCA survivors without STEMI who have a suspected cardiac etiology as soon as it is clinically feasible.

31. Retrospective data suggests an acute culprit coronary occlusion may be found in up to 50-70% of post-arrest cases, supporting risk stratification to select patients who would benefit from adjunctive angiography. • Clinical variables associated with the presence of underlying culprit CAD in OHCA survivors include: diabetes mellitus, a history of pre-existing CAD, and ST segment shift (ST elevation or depression) on the post-ROSC ECG. • Post arrest troponin elevation has limited sensitivity and sensitivity for predicting culprit CAD post OHCA. Predicting an Acute Coronary Lesion in OHCA Survivors

32. Recommendation • We suggest that the clinical likelihood of an acute ischemic etiology from an acute coronary lesion be used to guide the use of timing of angiography in this population (Strong Recommendation, Low Quality Evidence)

33. Observational studies have demonstrated that the concomitant use of TTM with PPCI for STEMI is technically feasible and not associated with a significant delay to reperfusion, nor with worsened neurological outcomes related to antiplatelet and antithrombotic-mediated intracranial bleeding. • Non-RCTs have reported improved survival and neurologic outcomes when PPCI is performed concurrently with TTM amongst post-arrest patients. Combined TTM and Coronary Angiography in OHCA Survivors

34. Recommendation • We suggest that TTM be initiated along with angiography in comatose patients if both are required concurrently. (Conditional Recommendation, Low Quality Evidence)

35. Practical Tips: • TTM initiation should be considered as soon as clinically feasible in all post-arrest patients who require revascularization. • The use of TTM should never delay the process of revascularization. • Individual care providers should choose a system and algorithm that would be best suited to their institutional needs when initiating concomitant angiography and TTM for post-arrest patients.

36. Critical Care Management

37. 3. Critical care management • Body temperature measurement • Sedation and analgesia • Neuromuscular blocking agents • Oxygenation targets • Ventilation targets • Serum lactate measurement • Mean arterial pressure goals • CVP monitoring • Optimal hemoglobin targets • Prophylactic anti-arrhythmic therapy

38. 3.2 Body temperature • Recommendation: • Continuous temperature monitoring from arrival to the end of the re-warming phase • No preference for monitoring location • Conditional Recommendation, Very Low Quality Evidence • Values and preferences: • Core body temperature probes suggested • PAC, nasopharyngeal, esophageal, rectal, or bladder probes

39. 3.3 Sedation and analgesia • Recommendation: • Patients managed with TTM should receive analgesics and sedation • Titrate according to a validated sedation scoring tool • Goal is to optimize patient comfort, reduce anxiety, and reduce duration of mechanical ventilation • Conditional Recommendation, Very Low Quality Evidence • Values and Preferences: • Paucity of data for use of specific medications

40. 3.4 Neuromuscular blocking agents • Recommendation: • Stepwise approach to reduce shivering with TTM • Skin counter-warming, acetaminophen, IV magnesium. • Attempt use of opioids, propofol or dexmedetomidine before NMBA • Conditional Recommendation, Very Low Quality Evidence • Values and Preferences: • Avoidance of potential risks of using NMBA • Use may be necessary in some cases.

41. 3.5 Oxygenation targets • Recommendation: • PaO2 between 60-200 mmHg in OHCA patients with known or suspected abnormal cerebral function. • Hypoxia (PaO2 <60 mmHg) and hyperoxia (PaO2 ≥200 mmHg) should both be avoided. • Conditional Recommendation, Low Quality of Evidence • Values and Preferences: • Recommendations derived from many types of studies. • Based on many clinical situations, hyperoxia and hypoxia appear to be harmful and should be avoided.

42. 3.6 Ventilation targets • Recommendation: • In patients undergoing mechanical ventilation after OHCA who have known or suspected abnormal cerebral function, ventilation should be adjusted to target normocapnia (PaCO2 35-45 mmHg) • Conditional Recommendation, Low Quality Evidence • Values and Preferences: • This recommendation is based upon the known adverse outcomes associated with ventilator-associated hypocapnia. • While we recognize that the association of mild hypercapnia with clinical outcomes is not as clear, we still believed it is reasonable to aim for normocapnia as a preferred ventilation target.

43. 3.7 Serum lactate measurement • Recommendation: • Serial serum lactate levels be followed in the post-OHCA period for at least 24-hours • Conditional Recommendation, Low Quality Evidence • Practical Tip: • Although observational data has linked initially elevated lactate levels and decreased lactate clearance with poor outcomes, it remains unclear whether specific therapy targeted towards decreasing serum lactate levels improves OHCA patient outcomes. • Failure to achieve lactate clearance targets should prompt a careful reassessment to identify and treat states of ongoing shock. • Following serum lactate levels every 4 to 6 hours may help identify patients with ongoing shock that needs to be addressed.

44. 3.8 Mean arterial pressure • Recommendations: • MAP target of at least 65 mmHg be maintained in OHCA patients, using intravenous fluids, vasopressors and/or inotropes as necessary. • Conditional Recommendation, Low Quality Evidence

45. 3.9 Central venous pressure • Recommendation: • All hemodynamically unstable OHCA patients have CVP monitoring • No specific minimum value recommendation, to help guide management efforts. • Conditional Recommendation, Very Low Quality of Evidence • Practical Tip: • A CVP range of 8-12 mmHg is the most commonly cited target in the ICU literature. • The optimal CVP goal remains unclear for OHCA patients. • CVP hemodynamic trends are likely of greater clinical importance than a single absolute value, and optimal CVP values for individual patients may differ based on concomitant and/or complicating clinical considerations.

46. 3.10 Hemoglobin • Recommendation: • Transfusion of red blood cells for a hemoglobin ≤80mg/dL in patients following OHCA • Conditional Recommendation, Very Low Quality Evidence • Values and Preferences: • This recommendation recognizes the inability to assess active cardiac symptoms in patients undergoing TTM and the high prevalence of CAD and ACS associated with OHCA in whom a hemoglobin concentration ≥80mg/dL is recommended. • Practical Tip: • Transfusion at a higher hemoglobin concentration may be considered if there is evidence of ongoing inadequate oxygen delivery after cardiac output has been optimized.

47. 3.11 Prophylactic antiarrhythmic drugs • Recommendation: • Reasonable to initiate prophylactic antiarrhythmic medications early in the hospital course in patients with recurrent episodes of VF/VT, non-sustained episodes of VT, or a high burden of ventricular ectopy. • Conditional Recommendation, Very Low Quality Evidence • Values and Preferences: • Importance to reduce recurrent hemodynamically compromising arrhythmias

48. OHCA Care Systems and the Care Environment

49. Non-OHCA Care Systems • Establishment of Level 1 Trauma Centers DiRusso J Trauma 2001

50. Non-OHCA Care Systems • STEMI CARE Systems Jollis JAMA 2007