Potential Organ Donor Post Trauma

Introduction and purpose The focus of trauma medicine is the immediate assessment and resuscitation of life-threatening injury, the treatment of stable injury in a logical sequence of urgency, and the prevention of loss of function. In the trauma setting it is apparent in a number of clinical situations that there is little likelihood of recovery from severe injury. It is in this instance that an early consideration of the possibility of organ retrieval and donation may follow the prior wishes of the injured patient and allow others an improved quality of life. While full medical treatment is continued, the direction of medical management then turns toward the diagnosis of brain death and the optimization of conditions for preservation of organ function and the prevention of secondary damage. This section will enable the reader to understand the issues of organ donor selection following trauma. It will highlight the trauma that leads most often to a patient becoming an organ donor. It will provide information on clinical and imaging techniques for early recognition of brain stem death, indicate the key points in assessment of organ viability for transplant, and present the latest medical management of organ donors for optimizing organ function. It is important to emphasize some general principles in brain death and organ donation. Principles Trauma is the commonest antecedent of patients who could provide organs for donation. There are many organs that may be donated from brain dead patients or cadavers. Organ donation is considered when it is evident that survival from the trauma event is not possible. The possibility of organ donation should not influence medical management. It must be consistent with the expected wishes of the trauma patient. It is reasonable to initiate assessment for organ donation prior to determination of brain death. An appropriate time interval should separate discussion with relatives of the impending death of the patient, and the request for organ donation. The request for consent is an important step in organ donation. Formal Brain death testing should only occur after a suitable assessment period. Brain death determination should be by selected individuals involved in the care of the patient but not involved in organ harvesting or allocation.

 

Identification of potential organ donors Insufficient supply of organs. There is great demand for transplantable organs as a result of progress in organ transplant medicine with new surgical techniques and immunosuppressive drugs (Miranda et al. 1997). The high demand for organs contributes to a rate of death on the transplant waiting list for heart, lung or liver transplants of around 20% (Matesanz et al. 1996). There are 40,000 people awaiting a kidney transplant in Western Europe with the supply being 5000 cadaver kidneys per year. Trauma hospitals have significantly higher levels of potential for organ donation and significantly higher levels of performance in organ donation (Sheehy et al. 1996). The majority of vascularized organ donation from trauma is from head injury. (Malagoni et al. 1996) Improving donor rates A number of methods have been proposed to improve donor rates. These include education of the public, an “opt out” law of donor inclusion, required request legislation, education of medical professionals, hospital organ donation development programmes, assessment and comparison of retrieval rates from different institutions, coordinated retrieval programmes, and programs for the early detection of donors. The use of organs with trauma related impairment, described as marginal organs, has also been researched allowing a wider group of donor patients to be assessed for suitability. The application of suitability limits for vascular organs gives a greater chance of accepting otherwise abandoned donor organs (Wheeldon et al. 1994). An important step in organ donation is for the attending physician to make a request to relatives for the consideration of organ donation. A major cause of donation loss is from failure to request (Kennedy Jr. et al. 1992). Separation of discussion of death and the request for organ donation is important in gaining relative consent for donation (Garrison et al. 1991). Half of donation failures are family refusal and so it is important to have training in the approach at the time of request (Werkman et al. 1991). There are important differences in religious and cultural beliefs that affect the way people view organ donation. It is best to be aware of these differences before approaching the family. It is possible to improve organ donation rate at large urban trauma centres with a hospital development program (O’Brien et al. 1996). It may be useful to assess the trauma admission profile of each unit to gain an expectation of what would be the organ donor rates from the record of cases through the unit. Organ donation can occur from cadavers, in particular kidney and corneal grafts. For vascular organs, the potential yield from non heart-beating blunt trauma victims is low and so may not be a direction for organ donation from trauma to take (Wisner et al. 1996). Organ preservation techniques are allowing longer ischaemic times for livers and are expected to allow longer preservation times for hearts and heart lung grafts in the future. Early recognition of potential organ donors in trauma The first opportunity where potential donors are lost is the detection of people who can be diagnosed as brain dead and hence could be considered as a potential organ donor. (Miranda B et al. 1997). The early

recognition of terminal injury may allow greater salvage of organs. The commonest source of donor organs is from head injury. Malagoni (1996) showed in a retrospective review of experience in a metropolitan level 1 trauma center that successful organ donation among patients without head injury comprised only 1% of donations. Head injury leading to donation is primarily from traumatic injury, intracranial haemorrhage or ischaemic injury, or from primary cerebral tumour (Table 34.1). Traumatic head injury is commonly from motor vehicle crash, gunshot trauma, or blunt trauma. Malangoni (1996) showed also that a 13% organ donation rate could occur from traumatic head injury when a second organ system is involved in trauma. In the trauma patient the early recognition of extensive brain injury is critical to management. It can be predicted from the mechanism of injury, observed from the clinical state of the patient on primary assessment, and confirmed on imaging. The early management of the injury is resuscitation, improvement of function and prevention of secondary injury. At this point the focus is on the optimal management of the brain injury and other injuries related to the trauma. This may initially require intravascular volume resuscitation for haemodynamic stability but subsequently the restriction of fluid to reduce cerebral water content, inducing a rise in plasma osmolarity, the maintenance of optimal haemodynamic indices and the correction of developing complications of trauma. Where this is unsuccessful the management of the patient following brain death is directed to continuing care to the primary condition but with a shift in focus towards tissue perfusion and oxygenation, and anticipation of brain death physiologic sequelae (Robertson et al. 1991). The importance of the early recognition of terminal brain injury is that it will provide time for initiation of assessment for suitability of organ donation. It is clinically clear when brain death is inevitable and therefore reasonable to shift focus prior to formal confirmation of brain death. (Raper et al. 1995). This will allow organ function to be optimized for the possibility of donation. To recognize brain death it is necessary to have an understanding of coma in the trauma setting. Coma definition and assessment Coma is a state of unrousable unresponsiveness. (Myburgh et al. 1997). It is a state of impaired consciousness that can be assessed from the patient’s activity spontaneously and in response to stimulus, on presentation to the trauma unit. The Glasgow Coma Score (GCS) was developed to grade the severity of head injury. It is a descriptive scale assessing the depth of unconsciousness (Table 34.2). A score of 15 indicates normal alertness and a score of 3 indicates a serious state of unconsciousness. It is influenced by alcohol and drug intoxication, metabolic disturbance, and a specific scale for paediatric care has been developed. Intubation for impaired consciousness will be required below a score of 10. It is important to obtain a clear history of aetiology and time course of the injury. A traumatic aetiology and several hours of observed coma in spite of treatment during transport to the trauma receiving room, it is likely that significant injury is present and will need confirmation clinically and by radiological assessment. The lowest GCS is 3 indicating no response to stimulus. When a score of 3 is combined with a severe

isolated brain injury as its cause, then it indicates the possibility of impending brain death and the contingency of organ donation should be considered. The presence of irrecoverable cerebral injury that appears likely to progress to brain death prior to terminal circulatory failure or cardiac arrest requires the consideration of organ donation (Scheinkestel et al. 1995). The recognition of irreversible cerebral injury is integral in assessment brain death. Once reversible causes of coma are excluded and clear causation of injury is identified then it is evident that the patient may progress to a persistent vegetative state, a lockedin state, or brain death. These states exist with brain stem injury and must be distinguished from brain stem death by careful assessment clinically, and with ancillary investigations. It is necessary to identify early predictors of irrecoverable head injury on the initial assessment during the first hours of emergency trauma care. Prognostic features of severe brain injury Is it possible to predict death from head injury? Attempts have been made to determine predictive indices within 24 hours for the likelihood of death from severe traumatic brain injury. These have ranged from the use of simple clinical indices (Mamelak et al. 1996) to more complex measurements such as heart rate variability (Winchell et al. 1997). These studies aim to lift the assessment beyond clinical judgement to that of a reliable, measurable, composite determinant. The clinical indicators for outcome from head injury are as one would expect (Table 34.3). Mechanism of injury, the presence of associated injuries, age above 60 years (indicating the influence of underlying medical conditions and reduced physiologic reserve), GCS on arrival of 3-5 (in coma it can be taken as best motor response = 1 or 2 out of 5), hypoxia, hypotension (systolic blood pressure < 90mmHg), dilated pupils, and prehospital care have been shown as clinical indicators for mortality or non functional outcome in trauma patients assessed on arrival (Combes et al. 1996, Fearnside et al., 1993, Celli et al. 1997, Quigley et al. 1997, Mamelak et al. 1996). Of these, age above 60 years and a GCS motor score of 1 or 2 persisting for 12 hours have the best discrimination (Mamelak et al. 1996). The need for ventilation and haemodynamic support is also an indicator of poor outcome. (Celli et al. 1997, Waxman K et al. 1991). Radiological investigations that indicate poor prognosis come from Angiography, Computerized Tomography, and Magnetic Resonance Imaging. Absent cerebral flow is used by some American states as an ancillary diagnostic criterion for brain death. It provides rapid, reliable diagnosis in adults. (Braum et al. 1997). Computerized Tomography findings indicating severity of injury are the presence of extensive subarachnoid haemorrhage or intracerebral haemorrhage, loss of gray white matter differentiation, midline shift and severe oedema (Fearnside et al. 1993, Waxman K et al. 1991). The combination of extensive injury on Computerized Tomography and GCS of 3 on arrival gives a clear indication of likely mortality (Waxman et al. 1991, Kotwica et al. 1995). Emergency Electroencephalogram assessment can be used to direct therapy in brain trauma, assist the diagnosis of brain death (Legros et al. 1998) and indicate prognosis for closed head-injured patients (Thatcher et al. 1991). It is generally accepted however that an early reliable prediction of death is not possible and that resuscitation must be optimal regardless of initial neurologic status. (Chestnut RM 1997) (Waxman et al 1991). If cerebral function does not recover, adequate resuscitation is equally important for maintaining

function of other organs for donation. Clinical suspicion of brain death The attending physician needs to have clear idea of impending brain death. The features of severe brain injury are the presence of coma, apnoea, and clinical signs of brain stem injury (Table 34.4). The cortical and brain stem function can be ascertained by the response to clinical assessment at this point. The presence of abnormal posturing and seizures indicates that brain stem death has not occurred but instead, in the severe trauma setting, it indicates residual function that may progress to brain death. Be alert to the appearance of brain stem dysfunction from alcohol, drugs abuse, prescription drugs including mydriatic agents, previous ocular surgery, metabolic disease, hypothermia, and the differences found in paediatric assessment. Definition of brain death Death is a biological event. It separates the process of dying from the process of disintegration (Bernat et al. 1981). It is accepted as the cessation of respiration and circulation. Brain death is a legal definition of death where one organ system, the brain, has reached a point of irreversible deterioration. This in turn will lead to the disintegration of all other organ systems usually within days. Intensive medical support may prolong this stage of disintegration. Disintegration occurs by ischaemic injury to organs, hypoxia, hypothermia, haemodynamic instability and endocrine dysfunction. Brain death is a state that is defined by the clinical criteria used to identify it. It is important that the formal judgement on brain death is made by a clinician not primarily involved in the patient resuscitation to avoid the suggestion of conflicting interest. The Australian and New Zealand Intensive Care Society Guidelines (Pearson 1995) state that the primary responsibility of the attending physician is towards the patient. When there is no expectation of recovery, and following the wishes of the patient given prior to their terminal injury, it is the ethical and professional responsibility of the Intensive Care Specialist to support the process of organ donation. It is clinically clear when brain death is inevitable and so it is reasonable to initiate a discussion about organ donation prior to formal confirmation of brain death (Raper et al. 1995) but important to separate the admission of impending death from the request for organ donation. The conditions for legal brain death differ between countries but have similar basic requirements. These are given in Table 34.5. The criteria vary throughout the medical community over the use of ancillary tests such as CT, EEG and 4-vessel angiography but the conditions for brain death can be put simply: 1

the presence of a recognized proximate cause of brain injury

2

absence of clinical brain function

3

proof of no confounding intoxication

4

bedside testing for brain death usually repeated by the same individual at 6 to 24 hours.

The patient must have normal physiologic indices e.g. temperature, electrolytes, blood gases, blood pressure, and the absence of pharmacological causes of coma e.g. sedative overdose or muscle

paralysis. There must be sufficient time for diagnosis - at least 4 hours from injury and preferably 24 hours. The examination must be by trained and approved physicians. It is important to remember that neonates and children have specialized requirements for diagnosis of brain death. Criterion for donor acceptance and organ assessment Criterion for selection and exclusion The general suitability of organ donation can easily be assessed. The criteria are firstly the prevention of transmission of disease. This can be either malignant or infective disease. The second criterion is acceptable function of the donor organ. A brief period of resuscitated cardiac arrest is acceptable for putting a patient forward for organ donation. It is up to the receiving medical team to make the final decision for the suitability of individual organs and this may only be possible with donor assessment in the operating room by the retrieval team. It is best not to preempt the decision of organ suitability by excluding the possibility of organ donation without first requesting advice. The general criteria for suitability are summarized in Table 34.6. Acceptable age limits are widening for many organs in particular renal transplantation. Cardiac, pulmonary, hepatic and renal impairment may be permissible if it occurred in relation to admission trauma (Wheeldon et al. 1994, Sundaresan et al. 1995, Van der Werf et al. 1998). Although primary brain tumours do not rule a patient out as an organ donor, it is important to ensure that it is not a metastatic lesion from an unknown primary site. Viral infection history of CMV, Hepatitis B, Hepatitis C may not preclude organ donation. The absolute contraindications are given in Table 34.7 for specific organs. The relative contraindications require the decision of the retrieval team for consideration of acceptability. Many tissues can be donated following death, especially corneas, and this should be remembered as a consideration. General preparation of patient for possible organ donation The regional Transplant Coordinator will assist in the general preparation. They will interrogate a national database to determine where organs should be directed. Medical care must be optimally maintained during the period of investigation. The process may take many hours. The tests requested by the transplant coordinator are given in Table 34.8. Contact should be made electively with the regional transplant coordinators so their guidelines can be obtained and checked for which tests they consider essential. It is a 24-hour service and usually has a single telephone number for contacting the service in each state or region. There are specific tests that can assist individual organ assessment. These are given in Table 34.9. The use of these will be directed by the retrieval team and the facilities available at the donor hospital. Medical management of organ donor Understanding the physiologic changes of brainstem death As the pathologic process of brain injury leads to brain death, there are a number of damaging physiologic changes. These produce a generalized disintegration of body organs due to massive sympathetic autonomic nervous system (ANS) activity followed by a failure of the hypothalamic-pituitary axis (Novitzky

1996). Animal models of brain injury leading to brainstem death demonstrate a progressive and sequential neurologic ischaemic injury beginning rostrally and extending caudally resulting from the pressure of cerebral oedema pushing the brainstem into the foramen magna. This process is called coning (Shivalkar et al. 1993). Initially there is a vagotonic effect of cerebral ischaemia followed by a sympathetic effect producing hypertension and tachycardia (Cushing’s reflex). As the entire brainstem becomes ischaemic, the sympathetic response becomes dominant and gives greatly increased cardiac output, blood pressure, and heart rate. This may produce myocardial ischaemia and damage other donor organ function (Power, Van Heerden 1995). It is followed by the onset of loss of vasomotor tone, arrythmias, hypotension, lowered cardiac output, loss of inotropy and chronotrophy and the possibility of cardiac arrest prior to harvesting of organs. Vascular capillary permeability is increased and may induce tissue interstitial oedema (Table 34.10). Monitoring the patients haemodynamic state is to initially protect against ANS storm then support against circulatory failure while avoiding excess fluid administration and maintaining moderate inotrope use. Concurrently with cardiovascular changes there is loss of hypothalamic and pituitary control over endocrine and metabolic function. Hypothalamic failure produces loss of temperature control and hypothermia. Pituitary failure causes diabetes insipidus, a decrease in thyroid hormone, and a decrease in cortisol levels found in these patients. Peripherally there is resistance to insulin action that leads to further hyperglycaemia and metabolic failure. The relative hypothyroid state causes intracellular metabolism failure and may impair graft organs. (Novitzky 1997). The endocrine dysfunction may lead to impaired myocardial performance through reduction in thyroid hormone release. Electrolyte disorders will be worsened by onset of diabetes insipidus. The replacement of these hormones is practised in some centres of transplantation (Pickett et al. 1994, Novitzky 1997, Michler et al. 1996) and not in others (Scheinkestel et al. 1995, Buckley 1997). The effect of thyroid hormone administration may be due to a phamacologic property of thyroxine rather than a replacement of deficiency (Robertson et al. 1990), but has been shown to have a cardioprotective effect in the recovery of myocardial function after human cardiopulmonary bypass operations (Davis et al. 1993). Common complications of brain death The physiologic changes of brain death produce generalized organ system dysfunction and these are presented in Table 34.11. The anticipation and treatment of these problems greatly enhances success of organ transplant. Management of donor The management requires prevention of further injury, anticipation of complications, and recovery of organ function. This involves monitoring the patient and continuing active clinical treatment after confirmation of brain death. The focus shifts from cerebral resuscitation to the maintenance of donor organ function prior to removal in order to give the best chance of achieving normal function following implantation. In general the aim is the judicious use of intravenous fluid to avoid cardiac dilatation and interstitial

oedema of the lungs, and prudent use of inotropes to maintain cardiac and circulatory function to give adequate cellular perfusion and oxygenation. Guidelines are given in Table 34.13 for optimal measured indices to increase chance of organ acceptability for grafting. Monitoring The ventilated brain dead patient requires invasive monitoring with arterial blood pressure, blood gas and central venous pressure monitoring. Urine output needs hourly measurement with an indwelling catheter. Central temperature measurement is necessary to anticipate hypothermia. The use of pulmonary flotation catheters, transthoracic echocardiography, fibreoptic bronchoscopy and other organ assessment can lead to appropriate use of fluid and inotropes that will encourage recovery of marginal organs (Wheeldon et al. 1994). The presence of impaired organ function resulting from the injury causing brain death may itself not prevent acceptance of organs for donation as recovery can occur following transplantation. It is important to have a reliable, large gauge intravenous access. Inotropes should be given into the central venous circulation if required for more than brief periods. Blood transfusion may be necessary with CMV negative blood or with the use of CMV filters. Table 34.12 gives a summary of recommended monitors. Optimizing organ function and treatment of complications of brain death The intention is to prevent complications, recover function and avoid inducing further injury. The rule of 100 for heart rate, systolic blood pressure and urine output has been provided as an optimal approach to maintaining organ function in the brain dead patient awaiting organ retrieval (Power et al. 1995). This is a useful starting point but there is evidence of benefit in assessment with a pulmonary artery flotation catheter for determining functional recovery to standardized resuscitation for marginal organ donors (Maclean et al. 1997). Recommended indices are given in Table 34.13. The indices are guidelines and drug dosages used will depend on response to therapy. The concern over excessive inotrope administration is the production of iatrogenic catecholamine-induced cardiomyopathy. The requirement for tissue perfusion may require periods of higher dosage of inotrope infusion although it is important to restrict inotrope dosage for cardiac donation. Predominant alpha-adrenergic vasopressors should be used cautiously to avoid severe unopposed vasoconstriction. Isoprenaline produces tachycardia that may be useful in paediatric donors because of their rate-dependant cardiac output. Aggressive fluid management, warming, and treatment of Diabetes Insipidus may promote stability in paediatric cardiac donors (Finfer et al. 1996). Paediatric donors may need greater dosage of inotrope to achieve adequate perfusion pressure (Robertson et al. 1991). Intracranial injury produces ST and T wave changes that should not be confused with myocardial ischaemia. Transthoracic Echocardiography and direct examination of the myocardium at the time of harvesting will indicate the existence of ischaemic heart disease. Commonly there is right heart dysfunction which may have serious implications in heart transplantation. Arrhythmias can develop from multiple aetiology. This can be from the neurologic injury, electrolyte and respiratory disorders, drug therapy, hypothermia, or direct trauma to the heart. They do not necessarily contraindicate cardiac transplantation and treatment is indicated by the cause. Minute ventilation and oxygen administration should be restricted to that required providing arterial saturation >95% and normal arterial blood gases. Low ventilatory rates, low inflation pressures, and tidal

volumes up to 15ml/kg facilitate lung preparation for donation. Minimizing the inspired oxygen concentration and peak inspiratory pressure below 30cm H2O will reduce the risk of oxygen toxicity, in particular for heart-lung block donation (Robertson et al. 1991). Neurogenic pulmonary oedema is a sequelae of brain injury with the loss of capillary endothelial integrity and the movement of protein and fluid into the alveolus. The early sign of this complication is the fall in oximetry and PaO2 with a rising FiO2. Frequent suctioning and sputum collection for microbiological examination is important for predonation assessment and provides valuable information for antibiotic use following implantation. Care must be taken in avoiding introduction of nosocomial infection. Endocrine dysfunction is managed by replacement of the Thyroxin, Cortisol, Insulin and Anti-diuretic hormone (ADH). The appearance of polyuria with urine outputs of over 200ml per hour is managed with infusions of ADH. Diabetes Insipidus is evidenced by a low urinary sodium content in the face of hypernatraemia. The provision of ADH acts as to reduce water loss, maintain vascular tone, and assists endothelial integrity. It may allow inotrope use to be minimized. Relative hypothermia may be helpful in reducing organ metabolism at the time of organ donation. Severe hypothermia will produce coagulopathy and haemodynamic instability, particularly in paediatric donors. Normothermia is also necessary for the diagnosis of brain death. There is some latitude in the possibility for donor organ recovery from traumatic injury. In particular the kidneys are transplantable with a mildly elevated serum creatinine if it is a result of the terminal injury (Van der Werf et al. 1998). They can be retrieved from cadavers although the shortest ischaemic time improves recovery of kidney function. The heart can be transplanted from a state of moderate inotropic support if it is shown to recover with optimized haemodynamic loading (Maclean et al. 1997, Wheeldon et al. 1994). The lungs can be used with a pO2 less the 350mmHg on FiO2 of 1.0 and positive end expiratory pressure of 5 cmH2O for 15minutes if the cause is clearly defined or injury is in the contralateral lung. Hepatic function is recoverable in cooled donors in the face of significant hypotension. Corneas are recovered from cadavers after less than 12 hours, and skin and bone tissue can be recovered up to 24 hours following death. Referring questions on organ suitability to the Regional Transplant Coordinator may be helpful and does not constitute a commitment to provide donor organs. Summary One measure of excellence in a trauma service is its approach to the donation process. Consideration of organ donation from the dead or dying trauma patient, where appropriate, is a standard of care. In a trauma patients there are a great many different tissues for donation that can continue to support life after the patients death. Organ donation from brain dead trauma patients is usually in the context of head injury. It requires training and experience in the assessment of brain death, great care in the management of the donor patient, and immense consideration in the approach used when requesting the tissue. It requires respect for the trauma

patient and their family. The interests of the trauma patient are the paramount consideration, above the value of organ donation.