Transplantation After Brainstem Death

A 38-year-old previously fit man suffered a grade five subarachnoid haemorrhage. Attempts at coiling failed and he suffered a catastrophic rebleed on-table whereupon his pupils became fixed and dilated. After a suitable sedation washout period he underwent testing which confirmed brainstem death at which point he was referred to the specialist nurse for organ donation. Following counselling of the family and appropriate assessment, donation of his kidneys, liver and heart was agreed.

Upon confirmation of brainstem death, mechanical ventilation was continued to ensure PaO2 greater than 10 kPa and limit peak inflation pressure to less than 30 cmH20. Vasoactive support was switched from noradrenaline to vasopressin 0.02 iu/kg/min. Methylprednisolone and intravenous triiodothyronine were administered whilst awaiting harvest. Blood antibody testing for HIV1+2, Hepatitis B and C, HTLV-1 and CMV IgG were all negative. A transthoracic echocardiogram confirmed good biventricular function; following discussion with the transplant retrieval team a pulmonary artery catheter was floated. Clinical measurements of cardiac output and mixed venous oxygen saturation were satisfactory. Adequate hydration was maintained with crystalloid by infusion and glucose control optimised in the range 8-10 mmol/L with insulin. The dedicated retrieval team performed the organ retrieval eighteen hours after confirmation of brainstem death.

How can we optimise organ function for organ donation?

Stephen Shepherd

During 2011-12, the number of people on the UK organ donor register rose to 18.7 million; deceased organ donation rose to 34.4% and a total of 3,953 organ transplants were carried out.1 The demand for organs is increasing year on year, yet the number of deceased donors remains relatively static.2 In particular, the number of patients donating after brainstem death has plateaued in recent years.3 Careful donor management and organ preservation to increase the number and quality of organs transplanted per donor in this group is a pressing concern.2

The broad goal of donor management after brain-stem death to maintaining optimal circulatory and metabolic conditions whilst limiting further iatrogenic injury. Brain-stem death produces multi-system dysfunction which may compromise end-organ blood flow; subsequent organ damage could limit the organs that are retrievable and transplantable and may also increase the incidence of graft dysfunction.4 Conversely, too liberal fluid administration is associated with pulmonary dysfunction and may preclude lung retrieval.5 It stands therefore that an integrated approach to management of these patients is recommended.6,7 Balanced haemodynamic management is essential to harvest both kidneys and lung.7

There is conflicting evidence as to whether brain death produces significant change in circulating endogenous hormones and whether they contribute significantly to the circulatory instability.2 Hormonal resuscitation with vasopressin, cortisol, triiodothyronine and insulin administration in experimental models has been associated with improved metabolic and cardiovascular indices.{Novitzky:2006bp} The use of this approach has led to an improved organ harvest with better early function.8 Traditionally, high-dose corticosteroid replacement with methylprednisolone at 15 mg/kg has been advocated having been associated with improvements in donor-lung oxygenation.9 However, more recent work has suggested that a lower-dose regimen based upon 300 mg hydrocortisone may produce comparable results with significant reductions in hyperglycaemia and insulin requirements.10

As mentioned previously, over-hydration may also worsen the likelihood of pulmonary harvest. It is recommended that central venous pressure be maintained at 6-8 mmHg with vasopressors adjusted to maintain a mean arterial pressure greater than 65 mmHg.6,7 Dopamine, adrenaline and noradrenaline rapidly deplete myocardial ATP with β-receptor downregulation and hence depression of post-transplantation cardiac function.7 Low-dose vasopressin is preferred in this setting as it independently influences vascular tone in addition to treating diabetes insipidus.7,11 At infusion rates of less than 2.5 iu/hour, detrimental effects upon coronary, renal and hepatic circulations are low.11 Whilst careful fluid and vasopressor management is essential to both intermediate and longer term organ function, where supportive requirements are moderate, invasive cardiac output measurement may not be required and other, non-invasive methods are reassuring.5,11


 

Lessons Learnt

Pulmonary artery catheterisation may not have been required in this case as echocardiographic function as adequate and vasopressor requirements were moderate. High-dose steroid replacement with methylprednisolone may also have been excessive but a protocolised bundle of care is of great importance.


 

References

  1.  Annual Review 2011-12. NHS Blood and Transplant.
  2. Dikdan GS, Mora-Esteves C, Koneru B. Review of randomized clinical trials of donor management and organ preservation in deceased donors: opportunities and issues. Transplantation. 2012 Sep 15;94(5):425–41.
  3.  Organ Donation and Transplantation Activity Report 2011/12. organdonation.nhs.uk. NHS Blood and Transplant.
  4.  Snell Girmgawtuasred. Pulmonary allograft ischemic time: an important predictor of survival after lung transplantation. J. Heart Lung Transplant. 1996;15(2):160–8.
  5.  Abdelnour T, Rieke S. Relationship of Hormonal Resuscitation Therapy and Central Venous Pressure on Increasing Organs for Transplant. J. Heart Lung Transplant. International Society for Heart and Lung Transplantation; 2009 May 1;28(5):480–5.
  6. Rosengard BR, Feng S, Alfrey EJ, Zaroff JG, Emond JC, Henry ML, et al. Report of the Crystal City meeting to maximize the use of organs recovered from the cadaver donor. Am. J. Transplant. 2002. pages 701–11.
  7.  Smith M. Physiologic changes during brain stem death–lessons for management of the organ donor. J. Heart Lung Transplant. 2004 Sep;23(9 Suppl):S217–22.
  8.  Rosendale JD, Kauffman HM, McBride MA, Chabalewski FL, Zaroff JG, Garrity ER, et al. Hormonal resuscitation yields more transplanted hearts, with improved early function. Transplantation. 2003 Apr 27;75(11):1336–41.
  9.  Follette DMRSMBWD. Improved oxygenation and increased lung donor recovery with high-dose steroid administration after brain death. J. Heart Lung Transplant. 1998;17(4):423–9.
  10.  Dhar R, Cotton C, Coleman J, Brockmeier D, Kappel D, Marklin G, et al. Comparison of high- and low-dose corticosteroid regimens for organ donor management. J Crit Care. 2013 Feb;28(1):111.e1–7.
  11.  Shah VR. Aggressive management of multiorgan donor. Transplant. Proc. 2008 May;40(4):1087–90.
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