Post cardiac arrest period is a critical period after return of spontaneous circulation . Optimal care and management is associated with best outcome with least neurological devastating sequella.

1. IN THE NAME OF GOD
POST CARDIAC ARRSET
BRAIN INJURY
( PCABI )
Mansoor Masjedi MD
Associate prof. , Critical care consultant
Shiraz University of medical sciences
The 8th international congress on critical care
Tehran , Iran
Jan 11-13th 2023

2. As more people are surviving cardiac arrest,
focus needs to shift towards improving
neurological outcomes & quality of life in survivors

3. POST CARDIAC ARREST SYND. :
POST CARDIAC ARREST BRAIN INJURY
Treatment of cardiac arrest should focus on maximizing
neurologic recovery as well as systemic recovery to
the best functional outcome
Post-cardiac arrest brain injury (PCABI) , the main cause of :
 death in pts resuscitated from cardiac arrest
 long-term disability in those who survive the acute phase

4. POST CARDIAC ARREST HBI ( PCABI )
 Common & ranges from mild impairment to devastating brain inj.

 To minimise PCABI :
 Early CPR & defibrillation
 Restoration of Nl physiology
 TTM
 Identify outcome to enable continuation or withdrawal of Rx
 Multimodal prediction guidelines : to avoid premature withdrawal or
prolonging useless Rx
 Approximately one in three admitted to intensive care will survive, many of
whom will need intensive, tailored rehabilitation after discharge

5. PCABI pathophysiology
primary (ischaemic) and secondary (reperfusion) injury
occur sequentially during
cardiac arrest , resuscitation & acute post-resuscitation phase

6. No-flow phase starts from cardiac arrest until initiation of CPR
Brain: 2% of body wt, but receives 15–20% of total C.O.
Brain viability strongly depends on O2 & energy supply ( glucose)
Consciousness is lost between 4-10 s of absent CBF
Isoelectric EEG after 10–30 s of asystole
Primary injury ( Ischemic )

7. Secondary injury ( reperfusion injury )
 Upon initiation of CPR , CBF is partially restored : low-flow
( 25% of Nl flow ; 40–50% needed to avoid ischemic injury )
 With ROSC , CBF is restored,
but reperfusion of ischemic cerebrovas. bed →
secondary brain injury

8. Ischaemia → cessation of aerobic metabolism → ATP depletion
Dysfunction of Na+/K+ pump
influx of Na & water
and
intracell. oedema
K+ efflux → membrane depolarization →
opening of voltage-sensitive Ca++ channels
→ intracellular Ca++ influx
↑ Intracellular Ca++ →
activation of lytic enzymes & mitochondrial dysfunction →
further neuronal damage

9. Secondary injury ( reperfusion injury ) ; contd :
Another component of reperfusion injury is
activation of immune system → tissue inflammation ;
macrophages ( microglia ) & circulating leukocytes →
Further oedema

10. Cerebral perfusion changes in PCABI ;
NO refow
No-reflow ; reperfusion of brain after transient global ischaemia is
incomplete & inhomogeneous
 Histologically appears as multifocal perfusion defects of brain tissue
 The number and extent of defects increase with duration of ischaemi
 Distribution coincide with locations where PCABI is most commonly detected
(striatum, hippocampus, amygdala, and thalamus)

11. Cerebral perfusion changes in PCABI ;
Delayed hypoperfusion
Following ROSC ; a transient (15–30 min) ↑ global CBF (global hyperaemia)
then delayed hypoperfusion occurs ( ↓CBF > 50% )
The role of delayed hypoperfusion as a cause of PCABI is unclear
( both the cerebral metabolic rate of oxygen & the cerebral oxygen
extraction fraction also decreased 24–72 h after cardiac arrest suggesting
that the coupling between CBF and oxygen demand was maintained )

12. Changes in cerebral autoregulation
Cerebral autoregulation is narrower or right-shifted in 30–50% of pts PCA
PCA hypotension may result in cerebral hypoperfusion, worsening PCABI
In post-resuscitation care; a potential target for optimizing cerebral perfusion

13. Intracranial hypertension & ↑ ICP
 Patients with PCABI may develop ;
• Intracranial hypertension
• ↑ ICP ( cytotoxic or vasogenic oedema)
associated with poor
neurological outcome
Improved neurological outcomes using
invasive neuromonitoring (PbtO2 > 20mmHg & ICP <25mmHg) vs conventional Rx
( small matched cohort study )

14. TREATMENT OF PCABI
At present, there is no direct Rx for PCABI so
secondary injury to brain should be minimised by
maintaining physiologic homeostasis
Derangements in temperature, arterial blood pressure,
oxygenation, and ventilation should be avoided

15. Treatment of PCABI
• Optimizing cerebral perfusion
• Oxygenation
• Ventilation
• Targeted temperature management
• Neuroprotective agents
• Control of seizures

16. Optimising cerebral perfusion
PCA Optimal BP to prevent secondary ischemic injury is not known
107 comatose PCA either
protocolised goal-directed haemodynamic optimisation (MAP 85–100 & SVO2 65–75%) vs
MAP of 65 mmHg using fuids, inotropes, and vasopressors at discretion of physician
no diference in percentage of ischemic brain volume,
nor in neurological outcome at 6 mo
The current guidelines on post-resuscitation care by ERC & ESICM recommend :
avoiding hypotension (MAP<65mmHg) ,U/O >0.5ml/kg/h & Nl or decreasing lactate

17. Oxygenation
• Hyperoxia → ↑ free O2 radicals → worsen PCABI
• large clinical observational studies have been conficting
The current ERC-ESICM guidelines on Post-Resuscitation Care recommend
avoiding both hypoxia and hyperoxia , Spo2 94–98%

18. Ventilation
• CBF is partially regulated by PaCO2
• Hypo- or hypercapnia → ↓or ↑CBF due to cerebral constriction or
vasodilation, respectively
• In PCABI, hypocapnia from excessive ventilation may reduce CBF,
potentially worsening ischaemic injury
• In traumatic brain injury
– hypocapnia → both O2 extraction fraction & vol. of brain ischemia
– hypercapnia → cerebral vasodil. & ↑ICP
In absence of robust evidence, the ERC-ESICM guidelines recommend
titrating ventilation in order to maintain normal PaCO2 levels (35–45 mmHg)

20. Post Cardiac Arrest Care

21. Post Cardiac Arrest Care

22. Targeted temperature management
• 33 to 37.5 °C
• probes in bladder or oesophagus
• feed-back surface cooling device or intravas. Catheter
• Inconclusive optimal timing, temp. level & duration
• Mild systemic hypothermia to 32–34 °C was rapidly introduced into clinical
practice in 2003 after the publication of two clinical trials reporting
improved survival & neurological outcome in OHCA pts with VF as initial
rhythm treated at 32–34 °C for 12–24 h

23. Targeted temperature management
• In 2021, TTM2 randomised 1900 pts with OHCA of cardiac or unknown cause
from all rhythms to TTM at 33 °C vs. TTM to 37.5 °C in case of fever, defined
as≥37.7 °C
• Results : TTM at 33 °C had no beneficial effects on mortality, functional
outcome, or quality-of-life at 6 mo, and iwas ass. with signifcantly more
arrythmias with haemodynamic instability
ILCOR updated recommendations ;
active prevention of fever for≥72hr ( T ≤37.5 °C )
instead of the previously recommended target of 32–36 °C for ≥24 h

24. Neuroprotective agents
 Pharmacologic approaches to ↓ 2ndary inj. following ROSC :
• mitigating excitotoxicity
– xenon gas, an inhibitor of the NMDA receptor improving neuronal metabolism
– The XePOHCAS trial ( OHCA ; 50% Xenon inhalation during TTM is awaiting
publication)
• limiting mitochondrial injury
– thiamine, pyruvate and ubiquinol are at pre-clinical phases
• Neuroinfammation
– CYRUS trial ;OHCA ; cyclosporine vs. placebo ; no difference

25. Control of seizures
• In 1/3 of pts with PCABI in ICU ass. with poor neurolog. outcome
• epileptic or non-epileptic
• Myoclonus ( mostly ) , gen. or focal tonic–clonic ( often occur in the same pt.)
• EEG is crucial to ;
– Confirm cortical epileptic activity
– R/O effects of ICU drugs
– Prognosticate outcome
– Follow effects of Rx
• It is unclear whether seizures cause brain damage or seizures are marker of PCABI
• To date ; no direct evidence that antiepileptic Rx improves outcome
• The TELSTAR trial ; Rx all electrographic seizure activity vs No Rx ( under invest. )
Current guidelines :
Treat postanoxic status epilepticus with
sodium valproate & levetiracetam as 1st line + increased sedation
Prophylactic antiepileptic Rx is not recommended

26. We must be prepared to save lives with
best neurological outcome