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Singh et al. Myocardial protection in cardiac transplantation

revealed significant increases in organs transplanted induced by brain death may be unable to replenish
and in 1-year survival of kidneys and hearts. Cardiac cortisol stores. Nicolas-Robin et al. [93] ’s group also
transplant centres then formed specific teams for the noted the effectiveness of hydrocortisone infusion on
purpose of “optimizing” the donors with the “Papworth norepinephrine dose decrease was observed in 25% of
Cocktail” [89] of hormones [90] . Multiple studies showed ACTH non-responders with low baseline cortisol. The
increased organ procurement and a reduction in anti-inflammatory properties of hydrocortisone could
primary graft dysfunction in transplanted hearts when also have an effect as adrenal insufficiency results
triple therapy with thyroid hormone, corticosteroids from the release of several cytokines such as tumor
and arginine vasopressin was used [91,92] . necrosis factor α, interleukin-1, interleukin-6, and
overexpression of cell adhesion molecules such as
Cortisol intercellular adhesion molecule-1 and E-selectin [97-99] .
It has been postulated that haemodynamic instability
in DBD donors is caused by adrenal insufficiency. A French study involving 22 ICUs during 15 months
Nicolas-Robin et al. [93] revealed in their cohort of to compare two different resuscitation strategies:
brain-dead patients, adrenal insufficiency was present systematic hydrocortisone supplementation (steroid
in almost 90%. They also noted that hydrocortisone group) or no supplementation (control group) in brain-
supplementation enhanced systemic haemodynamics dead patients who were potential organ donors was
and decreased norepinephrine dose by more than conducted. Eleven centres administered standard-
30% in more than half of brain-dead patients with care, low-dose hydrocortisone to brain-dead patients
haemodynamic instability. before organ procurement the remaining 11 did not
administer corticosteroids [100] .
They also identified several pathophysiological groups
based on cortisol levels and Adrenocorticotropic Adrenal insufficiency was noted in almost 80% of
Hormone (ACTH) response. (1) ACTH responders brain-dead patients. The average number of episodes
with low plasma cortisol: this reflected a hypothalamic- ofhypotension and vascular filling volume per hour were
pituitary failure (secondary adrenal insufficiency) similar in the two groups. Although more patients in
resulting from direct insult from intracranial hypertension the steroid group received norepinephrine before brain
causing ischaemia of the hypothalamus and pituitary
gland, impairing the release of corticotropin-releasing death, the mean dose of vasopressor administered
hormone and ACTH as described by Novitzky et al. [94] . after brain death was significantly lower than in the
This group responded to tetracosactrin (synthetic control group, duration of vasopressor support use
ACTH) administration; (2) ACTH non-responders with was shorter than in control group and norepinephrine
normal baseline cortisol - suggesting primary adrenal weaning before aortic clamping was more frequent.
failure; (3) ACTH non-responders with low baseline This decrease in number of vasopressors used
cortisol: this was probably caused by a hypothalamic- following steroid administration was seen in other
pituitary-adrenal insufficiency; and (4) ACTH studies as well [101] .
responders with normal plasma cortisol: no pathology
within the hypothalamic-pituitary-adrenal axis. Dhar et al. [102] looked at 132 consecutive brain-dead
donors managed before and after changing the steroid
Ironically, Nicolas-Robin et al. [93] ’s study demonstrated protocol from 15 mg/kg methylprednisolone (high dose)
that hydrocortisone infusion was more often efficient to 300 mg hydrocortisone (low dose) and found that
in enhancing haemodynamic stability in ACTH non- the only significant differences were lower final insulin
responders than in ACTH responders suggesting requirements and faster weaning off insulin infusions
that exogenous steroids have a higher likelihood of in the low dose group.
producing a haemodynamic response when there is
no endogenous response to ACTH stimulation. Steroid therapy was not associated with improvements
in the recovery of primary graft function in these
It is also postulated that the effects of corticosteroid studies.
administration could be due to the re-sensitization of α-
and β-adrenoceptors pathway which are often altered Thyroxine
by down-regulation and later by desensitization in Another change that occurs with brain death is the
patients with shock treated with catecholamines [95,96] . reduction of plasma-free triiodothyronine (T3) resulting
Another explanation is the “consumption” of cortisol in impaired aerobic metabolism. This causes a reduction
following its initial release by the hyper-stimulated of myocardial energy stores and an increased tissue
hypothalamic-pituitary-adrenal axis adrenal gland lactate as a result of increased anaerobic metabolism.

Vessel Plus ¦ Volume 1 ¦ December 28, 2017 221