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Post Resuscitation Syndrome

A cascade of vascular, cellular, biochemical and molecular events that results in irreversible brain injury during reperfusion following a transient ischemia as little as 5 minutes. These cascade of events are collectively referred to as reperfusion disease or postresuscitaion syndrome.

Pathophysiology

• After cardiac arrest, there is an initial period of no cerebral blood flow even if normal blood pressure is restored.

• This no reflow phenomenon is followed by 5-10 minutes of increased blood flow above baseline and eventual global or regional hypoperfusion.

• The alteration of cerebral blood flow is irrespective of cardiac output & it is believed due to disruption of cerebral autoregulation.

• During ischemia the brain is deprived of metabolic substrate; which makes the cells impossible to carry out energy dependent functions like maintenance of transmembrane ion gradient.

• Loss of transmembrane ion gradient leads to influx of calcium through voltage gated calcium channel and triggering release of glutamine.

• The neurotransmitter Glutamine released from presynaptic terminal binds with postsynaptic neuronal membrane and activates the influx of sodium and calcium channel.

• It causes cellular swelling, mitochondrial injury,depletion of antioxidant, derangement in nitric oxide metabolism and activation of multiple enzymes.

• The cells die either immediately by cell necrosis or later by apoptosis.

INVESTIGATION

CT

• On 2nd – 6th : Low density lesions in the bilateral caudate, lenticular & or thalamic nuclei.

• In asphyxia it develops after 5-7 days of resuscitation.

MRI

• Diffusion weighted sequence will show abnormalities in Basal ganglion , Cerebellum , Cortex as early as 48 hrs post resuscitation.

• But they are not reliable in predicting neurological outcome.





• A & B is Axial Flair images showing symmetrical T2 signal abnormalities at the level of superior cerebellum and thalamus. C & D shows same abnormality in DW image.
  

Therapeutic Hypothermia

Induction of moderate hypothermia (28 -32 C ) before cardiac arrest was successfully used since 1950's to protect brain against global ischemia.

In late 1950's hypothermia was used after cardiac arrest and was associated with improved functional recovery and reduced cerebral histological deficits.

Mechanism of Action

• In normal brain, hypothermia reduces the cerebral metabolic rate for oxygen (CMRO) By 6% for every 1C reduction in brain temperature > 28 C .

• But in animal studies it has shown that mild hypothermia doesn't produce any significant reduction in CMRO.

• It causes suppression various chemical reaction thereby reduces free radical production, reduces excitatory aminoacid release & calcium shifts. Thereby reducing mitochondrial damage and cell death.

Indication

• ILCOR ()International Liaison Committee for Resuscitation) recommends therapeutic hypothermia for unconscious adult patients with ROSC after out of hospital cardiac arrest . (Level 1 Evidence)

• ILCOR recommends a core temperature of 32 – 34 C for 12 -24 hrs when the initial rhythm was VF.

• Such cooling may benefit for other rhythm or in hospital cardiac arrest. (Level 4)

   

Contraindication

• Severe cardiogenic shock

• Life threatening arrhythmia

• Pregnant patients

• Primary coagulopathy

Adverse effects

• Shivering

• Hypotension

• Sepsis

• Hyperglycemia

Timing of Cooling

• Cooling should be imitated as soon as possible after ROSC , but successful even if it is delayed for 4 -6 hrs.

• Animal studies suggest initiating cooling at the earliest is associated with better clinical outcomes.

• Therapeutic hypothermia may be applied for initial 12 -24 hrs .

Cooling techniques and Monitoring

• Continuous monitoring of temperature by bladder temperature probe or a pulmonary artery catheter in situ.

   

• External cooling methods

  • Cooling blankets

  • Application of ice packs

  • Wet towel

  • Fanning

• IV infusion of 30 ml/kg of crystalloid at 4C over 30 min reduced core temperature significantly.

• Extracorporeal cooling methods are efficient but too invasive for use in the prehospital environment.

• Shivering during cooling leads to warming and increase in oxygen consumption and should be prevented by using neuromuscular blocker and sedation.

• Magnesium can be used as it can increase the threshold for shivering.

Rewarming

• Rewarming is started after 12 -24hrs.

• Rewarming should be slow with a target rate of 0.25 C every hour till the patients temperature is 36- 37 C.

Other Agents

• Thiopental sodium and glucorticoids where found not effective in BRCT 1 (Brain Resuscitation Cardiac Arrest Trial ) trial.

• Calcium channel blocker lidoflazine was studied in BRCT 2 trial but was found ineffective.

• Thrombolysis

  • It has been shown that following cardiac arrest a coagulation cascade is initiated and it may be beneficial to thrombolysis especially in case of PE & MI.

• Hypertonic, hyperoncotic infusion

  • A different approach to promote microcirculation is the use of special infusion regimens which improve the rheological characteristics of the blood.

  • Dextran 40, HES or isotonic saline has been tried.

  • Studies have shown promising effects but currently not recommended.

• Inhbitors of Apoptosis

  • It has been suggested that delayed neuronal death after cardiac arrest is caused by apoptosis.

  • Apoptosis is characterised by activation of proteolytic cascades, which ultimately result in degradation of cellular components. Proteolytic enzyme, caspase 3 is one of the key executioners of apoptosis.

  • Inhibiting apoptosis may reduce neuronal damage and is still a experimental level.

• Growth Factors where also tried in various animal studies but has not shown any benefits.

Updated on : 02/9/2013

Reference

• Tintinalli

• Cerebral Resuscitation After Cardiocirculatory Arrest, By Andreas ; Internationa Anesthesia Research Society; 2009

• Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest ; NEJM 2002

• Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia ; Stephen A Bernard ; NEJM 2002