What are the pathophysiological changes affecting the respiratory system that occur after brain death?

Usually two distinct phases, though the first is not seen in all patients

1. Hyperdynamic phase (sympathetic overactivity)
   • Transient catecholamine 'storm' (particularly adrenaline and noradrenaline) leads to:
     • Intense arterial constriction and hypertension with tachycardia and increase in cardiac output
     • Cushing's reflex due to massive increase in afterload with secondary baroreceptor activity causing bradycardia (occurs in about one-third of patients
     • Imbalance between myocardial oxygen supply and demand, manifesting as:
       • Acute myocardial injury and ST segment change
       • Arrhythmias and heart blocks
       • Apical ballooning and generalised LV dysfunction
2. Cardiovascular collapse phase (sympathetic underactivity)
   • Hypotension results from:
     • Loss of sympathetic tone and profound vasodilatation
     • Myocardial depression and arrhythmias:
       • Depletion of high energy phosphate
       • Mitochondrial inhibition
       • Reduction in T3 production
       • Electrolyte disturbance
     • Hypovolaemia:
       • Diabetes insipidus
       • Osmotic diuresis (mannitol, hyperglycaemia)
       • Therapeutic fluid restriction
   • Asystolic cardiac arrest generally occurring within 72 hours

• Neurogenic pulmonary oedema common due to catecholamine surge:
  • Elevated pulmonary capillary hydrostatic pressure caused by acute LV dysfunction
  • Capillary endothelial damage and increased permeability triggered by endogenous noradrenaline

• Pneumonia, aspiration of gastric contents, atelectasis can exacerbate respiratory failure

• Failure of hypothalamic-pituitary axis due to ischaemia with:
  • Impairment of temperature regulation
  • ADH depletion:
    • Diabetes insipidus (DI) which occurs in up to 65% of organ donors
    • Characterised by diuresis, hypovolaemia, plasma hyperosmolality and hypernatremia
  • ACTH depletion:
    • Reductions in cortisol production are unrelated to the degree of hypotension but may impair the stress response
  • TSH depletion:
    • Reductions in the circulating levels of tri-iodothyronine (T3) and thyroxine (T4)
• Insulin depletion:
  • Contributes to the development of hyperglycemia
  • Aggravated by
    • Administration of large volumes of glucose containing fluids, if used to treat hypernatremia
    • Increased levels of catecholamines