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Intensive Care Med 2015;41:2039–56
Resuscitation 2015;95:202–222
Post-cardiac arrest syndrome
◼ Persistent precipitating pathology
◼ Systemic ischaemia/reperfusion response
◼ Post-cardiac myocardial dysfunction
◼ Post-cardiac arrest brain injury
Nolan JP, Neumar RW. Resuscitation 2008;79:350-79
2000 – 2009 (OHCA)N = 768 (mortality = 66%)
Improving neurological outcome after
cardiac arrest
◼ Oxygenation and ventilation
◼ Cerebral perfusion (mean
arterial pressure)
◼ Sedation
◼ Control of seizures
◼ Glucose control
◼ Temperature control
Wang C-H. Resuscitation 2014;85:1142–8
Roberts BW. Circulation 2018;137:2114–24
No hyperoxia (n = 175)
Hyperoxia (n = 105)
PaO2 measured at 1 and 6 hours after ROSC
Hyperoxia =PaO2 > 300 mmHg (= 38% of cohort)
Hyperoxia associated with poor outcome
RR 1.23 (95% CI 1.11–1.35)
1 hour longer duration of hyperoxia
associated with 3% increased risk of poor
outcome (RR 1.03 (95% CI 1.02–1.05)
Ebner F. Crit Care 2019;23:30
Adjusted ORs for a poor neurological outcome
◼ Post hoc analysis of the TTM
Trial
◼ N = 869; 23% hyperoxaemia
◼ No association between
hyperoxemia, hypoxemia,
time-weighted mean PaO2
and poor outcome
Intensive care registry studies of hyperoxaemia
◼ Conflicting results: some show association between
hyperoxaemia and mortality
◼ High FiO2 probably unmeasured surrogate marker of
illness severity
◼ First 60 min post ROSC is missed
◼ Duration and timing of hyperoxia unknown
◼ Impact of therapeutic hypothermia?
Resuscitation 2018; 128: 211–215
• 1460 post-cardiac arrests with tracheal tube or SGA
• After ROSC – 100% oxygen or ≥10L/min until a satisfactory
SpO2 trace and reading is achieved
• 4 L/min O2 then 2 L/min (target 90–94%) or air-mix on
ventilator … versus:
• 10 L/min(target 100%) or 100% O2 on ventilator
• ED/Cath lab continues allocated target
• Study stops in ICU
• Survival to discharge
NCT02499042
Bray JE Resuscitation
2019:139:208–231
PROXY: Post ROSC
OXYgenationStudy
Thomas M.
BMC Emerg Med 2019;19:16
• 46 paramedics
randomised
• 35 patients recruited
• ‘Reliable’ SpO2
documented in 65–
70% of cases.
◼ “…as soon as arterial blood oxygen saturation can be monitored reliably… titrate the FiO2 to maintain the arterial blood oxygen saturation in the range of 94–98%.”
Nolan JP. Resuscitation 2015;95:202–22
Curley G. Crit Care Med 2010;38:1348-59
Hypocapnia is harmful to the injured brain
Resuscitation 2013;84:1540-5
PaCO2
40 mmHgPaCO2
30 mmHg
• 10 OHCA patients
• All treated with hypothermia
• Cerebral tissue oxygenation (SctO2)
• Monitored with NIRS
• Hyperventilation for 30 min
Eastwood GM Resuscitation 2016;104:83–90
◼ 86 post-arrest patients
◼ PaCO2 50–55 mmHg (TTMH)
versus PaCO2 35–45 mmHg (TN)
◼ Greater increase in NSE in TN
group (p = 0.04)
TTMH Targeted therapeutic mild hypercapniaTN Targeted normocapnia
TARGETED THERAPEUTIC MILD HYPERCAPNIA AFTER
RESUSCITATED CARDIAC ARREST: A PHASE III MULTI-CENTRE RANDOMISED CONTROLLED TRIAL
The TAME Cardiac Arrest TrialA/Prof Glenn Eastwood & Prof Rinaldo Bellomo
on behalf of the TAME Cardiac Arrest Trial Investigators
Department of Intensive Care
Austin Hospital
Melbourne, Victoria
Australia
COMACARE Study Group
Jakkula P. Trials 2017;18:507
NCT02698917
• 120 patients randomised to one of 8 groups
• Primary outcome = NSE value at 48 h
• Targeting low or high-norm PaCO2, PaO2, MAP for 36 h
• PaCO2: low-norm = 4.5–4.7 kPa; high-norm = 5.8–6.0 kPa
• PaO2: low-norm =10–15 kPa; high-norm = 20–25 kPa
• MAP: low-norm = 65–75 mmHg; high-norm 80–100 mmHg
COMACARE Study GroupJakkula P. Intensive Care Med 2018;44:2112–2121
COMACARE Study GroupJakkula P. Intensive Care Med 2018;44:2112–2121
◼ Retrospective cohort study 256
OHCA patients IPPV for ≥ 48 h
◼ Primary outcome CPC 1–2 discharge
◼ Time-weighted average over the first
48 hours, in mL/kg predicted body
weight (PBW)
◼ 38% – time-weighted VT > 8 mL/kg
◼ 194 patients propensity matched
Beitler JR. AJRCCM 2017;195:1198–1206
OR 1.61 (95% CI 1.13 – 2.28) per 1 mL/kg PBW decrease in VT
◼ Aim for normocarbia
◼ Protective lung ventilation strategies
not studied (in prospective trials) in
cardiac arrest.
◼ Post-cardiac arrest patients develop
marked inflammatory response
◼ Aim: tidal volume 6–8 mL kg-1
Nolan JP. Resuscitation 2015;95:202–22
Ameloot K. Resuscitation 2015;90:121–6
Patient with autoregulation
preserved
Patient with right-shifted
autoregulation
• 15/51 (35%) had disturbed autoregulation (majority chronic ↑ BP)
• Index of autoregulation (COX) to determine optimal BP
• Optimal MAP 85 mmHg if preserved and 100 mmHg if disturbed
Ameloot K. EHJ 2019; in press
• 112 OHCA patients
• MAP 85–100 mmHg + SVO2 65–75% versus
MAP 65 mmHg
• End point = MRI % apparent diffusion
coefficient (ADC) score < 650 at day 5
• % Voxels < 650.10-6 mm2/s 16% versus 12%;
OR 1.37 (95% CI 0.95–1.98); P=0.09
Jakkula P. Intensive Care Med 2018;44:2091–2101
Paul M. Resuscitation 2018;128:204–210
Period 1. Mar 2008 – Feb 2013
Midazolam and fentanyl (n – 326)
Median time to awakening 17 h
Delayed awakening 29%
Period 2. Dec 2014 – Oct 2016
Propofol and remifentanil (n = 134)
Median time to awakening 2.5 h
Delayed awakening 6%
Post-resuscitation care
Summary
◼ Until further data are available titrate FiO2 post ROSC
◼ Optimal PaCO2 to be determined - aim normocarbia?
◼ Use lung protective ventilation
◼ Optimal MAP is probably patient specific but generally
higher than previously accepted
◼ Use short-acting sedation… why wouldn’t you?
Blood pressure and OXygenation
targets after OHCA (BOX)
◼ 800 OHCA to be randomized;
◼ Primary endpoint death or CPC 3 or 4 at discharge
◼ Factorial design (during ICU stay):
◼ Low normal MAP (63 mmHg)
◼ Low normal PaO2 (9-10 kPa)
◼ High normal MAP (77 mmHg)
◼ High normal PaO2 (13–14 kPa)
◼ MAP blinded by offsetting BP monitor by +/- 10%
◼ Sub-study of fever control for 36 or 72 hours
◼ Assessment of pupillometryKjaergaard J, Rigshospitalet, Denmark. NCT03141099
