Post Arrest Ventilation/Oxygenation Management Richard Branson Msc RRT Professor of Surgery University of Cincinnati Editor-In-Chief Respiratory Care

Home , Hypocapnia, Mechanical ventilation

Post Arrest Ventilation/Oxygenation Management Richard Branson MSc RRT Professor of Surgery University of Cincinnati Editor-In-Chief Respiratory Care

Presenter Disclosure Information

Richard Branson MD • Post Arrest Ventilation Management

FINANCIAL DISCLOSURE: Grants/Research Support: Mallinckrodt, Ventec Life Systems, Aerogen, Philips, Speakers Bureau: Mallinckrodt UNLABELED/UNAPPROVED USES DISCLOSURE: None

1 2 Tremblay & Slutsky AJRCCM

Lower Tidal Volume Ventilation for ALI and ARDS ARDS Network. N Engl J Med 2000; 342:1301 Randomized trial of conventional V T (11.8 *p < .01 Low TV Conventional ml/kg) vs low V T (6.2 ml/kg) ventilation in 861 Mortality * patients with ALI Vent-free days *

Organ failure-free * days

Barotrauma

0 10 20 30 40 Percent of cases

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Stopped early for futility – no impact on outcome No safety concerns Improved gas exchange with higher PEEP – improved compliance All patients ventilated with LPV 6 ml/kg/PBW

N Engl J Med 2004;351:327

6 mL/kg O) 2 Non- 6 mL/kg recruitable Recruitable 6 (↑Crs) mL/kg Injury Benefit > > Benefit Injury PplatH (cm PEEP or

Lower Higher PEEP PEEP

4 FIO 2 0.3 0.4 0.4 0.5 0.5 0.6 0.7 0.7 0.7 0.8 0.9 0.9 0.9 1.0 PEEP 5 5 8 8 10 10 10 12 14 14 14 16 18 20-24

Assess “lung recruitability”

PaO 2/F IO2 < 150 on 5 cm H 2O PEEP ↑Compliance or ↓dead space with ↑PEEP

yes FIO 2 0.3 0.3 0.3 0.3 0.3 0.4 0.4 0.5 0.5 0.5 0.6 0.7 0.8 0.9 1.0 PEEP 5 8 10 12 14 14 16 16 18 20 20 20 20 20 20-24

Ramnath, Clin Chest Med 2006;27:601

Oxygenation & Ventilation following ROSC • Mechanical ventilation – Lung protection principles • Oxygenation goals • Ventilation goals

5 Hyperoxemia in Cardiac Patients

• Oxygen is often given in the absence of hypoxemia • The vasoactive actions of oxygen are not well appreciated

• Once SpO 2 is 100% further increases in PaO 2 are not monitored • Hyperoxemia in normoxic patients may adversely effect outcome

JAMA 2010;303:2165

6 JAMA 2010;303:2165

JAMA 2010;303:2165

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11 Oxygen following Cardiac Arrest

• Supplemental Oxygen: 100% vs Titration • Does the use of titrated oxygen during cardiac arrest, compared with the use of 100% oxygen, improve outcome (eg, ROSC, neurologically intact survival)? • Consensus on Science • There were no adult human studies. • Two animal studies (LOE 5) suggested worse neurological outcomes compared with normoxic resuscitation. • One animal study (LOE 5) 100% oxygen or 21% oxygen during resuscitation did not affect outcome. • Treatment Recommendation • There is insufficient evidence to support or refute the use of a titrated oxygen concentration or constant 21% oxygen compared with 100% oxygen during adult cardiac arrest. No change the current treatment algorithm (100% oxygen during cardiac arrest). • Knowledge Gaps • Prospective clinical trials may be warranted to explore constant (including room air) versus titrated oxygen resuscitation approaches during human adult cardiac arrest.

Systematic Review – Hyperoxia and Coronary Blood Flow

• From 2,072 publications, 6 met criteria, 6 healthy and 61 with cardiac disease.

• High-concentration O 2 resulted in hyperoxia, PaO2 of 273 to 425 mm Hg. • Hyperoxia caused a significant reduction in coronary blood flow (mean change −7.9% to −28.9%, n = 6 studies). • Hyperoxia caused a significant increase in coronary vascular resistance (mean change 21.5% to 40.9%, n = 4 studies) and a significant reduction in myocardial oxygen consumpon (mean change −15.3% to −26.9%, n = 3 studies). • Conclusions Hyperoxia from high-concentration oxygen therapy causes a marked reduction in coronary blood flow and myocardial oxygen consumption. These physiologic effects may have the potential to cause harm and are relevant to the use of high-concentration oxygen therapy in the treatment of cardiac and other disorders. (Farquhar H. Am Heart J 2009;158:371-7.)

12 Hyperoxemia and Coronary Blood Flow

McNulty PH. Effects of supplemental oxygen administration on coronary blood flow in patients undergoing cardiac catheritization. Am J Physiol Heart Circ Physiol 2005;288:H1057-62.

13 Background Oxygen is widely recommended for patients with myocardial infarction yet may do more harm than good. Systematic reviews have concluded that there was insufficient evidence to know whether oxygen reduced, increased or had no effect on the ischemia or infarct size. Selection criteria Randomized controlled trials of people with suspected or proven AMI, less than 24 hours after onset, in which the intervention was inhaled oxygen compared to air and regardless of co-therapies provided these were the same in both arms of the trial. Main results Three trials (387 patients) were included and 14 deaths occurred. The pooled RR of death was 2.88 (95% CI 0.88 to 9.39) in an intention-to-treat analysis and 3.03 (95% CI 0.93 to 9.83) in patients with confirmed AMI. While suggestive of harm, the small number of deaths recorded meant that this could be a chance occurrence. Conclusions There is no conclusive evidence from randomized controlled trials to support the routine use of inhaled oxygen in patients with acute AMI. A definitive randomized controlled trial is urgently required given the mismatch between trial evidence suggestive of possible harm from routine oxygen use and recommendations for its use in clinical practice guidelines .

OXYGEN DOSE AFTER ROSC IN ADULTS

• Hypoxia vs. normoxia • Avoid hypoxia in adults with ROSC after cardiac arrest in any setting (strong recommendation, very low quality evidence). • Avoid hyperoxia in adults with ROSC after cardiac arrest in any setting (weak recommendation, very low quality evidence). • Use 100% inspired oxygen until the arterial oxygen saturation or the partial pressure of arterial oxygen can be measured (weak recommendation, very low quality evidence).

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Ventilation Target after ROSC • No studies demonstrate better outcome with

ventilation to a specific PaCO 2in patients with ROSC.

• Suggest maintaining PaCO 2within a normal physiological range as part of a post-ROSC bundle of care (weak recommendation, very low quality evidence).

16 • After restoration of circulation, routine hyperventilation leading to hypocapnia should be avoided in order to prevent additional cerebral ischemia. • Hyperventilation is associated with increased intrathoracic pressure, diminished venous return and decreased cardiac output

Treatment Recommendations

• No studies demonstrate better outcome with ventilation to a specific PaCO 2 in patients with ROSC.

• We suggest maintaining PaCO 2 within a normal physiological range as part of a post- ROSC bundle of care (weak recommendation, very low quality evidence).

17 Dallas 2015

Hospital registry study (IHCA/OHCA) 213 patients 1° outcome – In-hospital mortality (survival) 2 ° outcome – CPC ≤ 2 at discharge

In multivariate analysis, hypocarbia was significantly associated with increased risk of in-hospital mortality (OR 2.522; 95% CI 1.18-5.37).

The mean PaCO 2 (hypercarbia ) was significantly higher in survivors (5.2 kPa [4.9- 5.5]) compared to non-survivors (5.0 kPa [4.6-5.5]), but the mean PaCO 2 was not associated with neurologic outcomes.

Dallas 2015

Hospital registry study (IHCA/OHCA) 16,542 patients 1° outcome – In-hospital mortality (survival) 2 ° outcome – Survival to discharge home

Patients with hypocapnia showed a trend toward greater mortality than those with normocapnia (OR 1.12 [95% CI 1.00–1.24],p = 0.04).

No difference for in-hospital mortality between patients with hypercapnia and those with normocapnia (OR 1.07, [95% CI 0.98–1.16], p = 0.13).

18 Dallas 2015

Hospital registry study (OHCA) 409 patients 1° outcome – CPC ≤ 2 at 12 months

The mean 24 hours PaCO 2 level was an independent predictor of good outcome (OR 1.054; 95% CI 1.01–1.10)

With multivariate regression analysis, time spent in the PaCO 2 band higher than 6.0 kPa was associated with good outcome (OR 1.015; 95% CI 1.002–1.029)

No hypocapnia cohort

Consensus on Science Statements

! Hypocapnia ! No studies have specifically randomised patients to ventilation to a specific PaCO 2 goal.

! For the critical outcome of neurologically intact survival, two very low quality cohort studies {Roberts 2013 2107, Lee 2014 55} with a total of 406 patients (downgraded for very serious concerns about risk of bias and imprecision) showed hypocapnia (<3.0 kPa & <4.7kPa respectively) was associated with a worse outcome. ! For the critical outcome of death (or failure to be discharged home), one very low quality cohort study {Schneider 2013 927} of 16,542 patients (downgraded for very serious concerns about risk of bias and imprecision) showed hypocapnia (<4.7kPa) was associated with a worse outcome.

19 Consensus on Science Statements

! Hypercapnia ! No studies have specifically randomised patients to ventilation to a specific PaCO2 goal.

! For the critical outcome of neurologically intact survival, • One very low quality cohort study {Roberts 2013 2107} with a total of 193 patients (downgraded for very serious concerns about risk of bias and imprecision) showed worse outcome in patients ventilated to hypercapnia (>PaCO 2 6.7kPa) • One very low quality cohort study {Lee 2014 2107} with a total of 213 patients (downgraded for very serious concerns about risk of bias and imprecision) showed no difference in outcome for patients ventilated to hypercapnia (>PaCO 2 6.0kPa). • One very low quality cohort study {Verhaasalo 2014 1463} with a total of 409 patients (downgraded for very serious concerns about risk of bias and imprecision) showed better outcome for patients ventilated to hypercapnia (PaCO 2 5.1-10.1 kPa).

Consensus on Science Statements

! Hypercapnia

! For the critical outcome of of death (or failure to be discharged home), • One very low quality cohort study {Schneider 2013} with a total of 16,542 patients (downgraded for very serious concerns about risk of bias and imprecision) showed no difference in patients ventilated to hypercapnia (PaCO 2 >6.0kPa) • One very low quality cohort study {Lee 2014 2107} with a total of 213 patients (downgraded for very serious concerns about risk of bias and imprecision) showed a higher mean PaCO 2 in survivors.

20 Treatment Recommendations

• Suggest maintaining PaCO 2 within a normal physiological range as part of a post-ROSC bundle of care (weak recommendation, very low quality evidence).

• No studies demonstrate better outcome with ventilation to a specific PaCO 2 in patients with ROSC. • Hypocarbia is associated with worse outcome and we suggest should be avoided where possible (moderate recommendation, very low quality evidence).

• The upper limit at which PaCO 2 becomes harmful is unknown, although mild hypercapnia may have some neuroprotective effect (weak recommendation, very low quality evidence).

• Hospital registry study (IHCA) 193 patients 1° outcome – CPC ≤ 2 at discharge • Hypocapnia (OR 2.43 (95% CI 1.04 –5.65)) and hypercapnia (OR 2.20 (95% CI 1.03 –4.71) were independently associated with poor neurological function.

21 Summary • Principles of lung protection – VT of 6-8 ml/kg

and PEEP of 5 cm H 2O • Targets – Avoid hypoxia first – Avoid hyperoxia

– Target an SpO 2 of 94% – Avoid hyperventilation – Avoid hypoventilation – Normocarbia 35-45 mm Hg