|Year : 1997 | Volume
| Issue : 1 | Page : 21-31
|Management of the Brain-Dead Organ Donor
Robert D Fitzgerald
Department of Anesthesia and General Intensive Care, University of Vienna Medical School, Wehringer Gurtel, Austria
Click here for correspondence address and email
|How to cite this article:|
Fitzgerald RD. Management of the Brain-Dead Organ Donor. Saudi J Kidney Dis Transpl 1997;8:21-31
| Introduction|| |
Transplantation has become the treatment of choice for the management of end-stage failure of several organs. This development has led to an increased need for donor organs, which is not paralleled by a concomitant increase of donors. On the contrary, numbers of donors are stagnant or even decreasing in many countries. Additionally, the function and survival of transplanted organs depend on the condition of the donor at the time of retrieval surgery , . Thus, great efforts are necessary to preserve all available organ donors in an optimal state. Essentially, there are three possible sources of donor organs:
1. living donors,
2. brain-dead organ donors, and
3. non-heart beating donors.
In contrast to organs retrieved from living or non-heart beating donors the function of organs from brain-dead donors may have to be preserved for hours or days as the declaration of brain-death in most countries depends on the fulfillment of a lengthy protocol  . This gives the physicians involved, the opportunity to optimize the potentially transplantable organs, but also involves the danger of the organs sustaining damage. Applying an aggressive donor management strategy might improve the number of transplantable organs considerably  . Thus, understanding the pathophysiology of braindeath and the necessary measures for treatment is important.
The aim of this review is to describe the changes occurring after brain-death and to summarize and discuss the standard therapeutic procedures in order to maintain optimal donor organ viability.
| Brain-death|| |
Criteria of brain-death vary in different countries mostly depending on the principal definition of brain-death; either the death of all central neurological tissue with the complete loss of cerebral function, or the irreversible loss of integrated neurological function, e.g. consciousness and the ability to breathe  .
However, brain-death is not just the functional loss of an organ but induces a deterioration process which, even with maximal support, causes detrimental effects on all other organ systems until irreversible cardiovascular failure occurs  .
| Pathophysiology of Brain-Death|| |
Rohling, et al investigated a group of 141 brain-dead organ donors and listed the changes found most frequently  ; diabetes insipidus (81%), hypotension (76%). Hypothermia (73%), hypokalemia (72%), hyperglycemia (70%), hypernatremia (59%) and coagulopathy (57%). Nygaard, et al reported complications occurring in 114 organ donors; hypotension (81 %), multiple transfusion requirements (63%), diabetes insipidus (53%), disseminated intravascular coagulation (28%), arrhythmias (27%), cardiac-arrest (25%), pulmonary edema (19%), hypoxia (11%), acidosis 11%, seizures (10%), and hypothermia (4%)  .
Although the results in the two reports seem to differ, they give a good overview of the complications occurring in the care of the brain-dead organ donor. All these alterations can compromise irreversibly the function of the donor organs and if not monitored and treated intensively, could lead to a complete failure of the whole body system. Also, the complications tend to become more severe with time, thus emphasizing the need for rapid organ retrieval once brain-death has been declared  .
| Cardiovascular Complications|| |
Vagal activation in the early stage of braindeath results in a decrease of heart rate, mean arterial pressure and cardiac output before the vagal cardiomotor nucleus becomes ischemia Subsequently, there is a predominance of the sympathetic system with a hyperdynamic state  . In experimental studies the onset of brain-death is marked by a rise in cardiac output, mean arterial pressure, heart rate, and oxygen delivery followed within sixty minutes by a return of these parameters below baseline levels  . Thus, hypotension constitutes the earliest and most dangerous dysregulation occurring after brain-death and results from several causes: (i) the loss of peripheral resistance (ii) hypovolemia (iii) myocardial dysfunction.
The vasomotor control is severely impaired after brain-death resulting in neurogenic shock with a major decrease in peripheral resistance and pooling of blood in the venous capacitance vessels requiring massive volume substitution and temporary vasopressor support , . Also acute Cl-level spinal cord shock occurring after cerebellar tonsillar herniation has been proposed as a cause for neurogenic shock with severe decrease of peripheral resistance  .
Hypovolemia either results from diuretic therapy and fluid restriction used in the management of cerebral edema before declaration of brain-death, or uncompensated losses as a consequence of diabetes insipidus or hyperglycemia , .
The cause of myocardial dysfunction is multifactorial and it remains unclear which of the changes described occur first. Patients suffering from subarachnoid hemorrhage exhibit a high incidence of elevated catecholamine  and renin levels  and echocardiographic wall motion abnormalities are frequently detected  . In brain-dead individuals, high catecholamine levels are known to occur  and to increase further by painful stimuli  . An experimental study in brain-dead pigs using cardiac microdialysis revealed dramatic increase of noradrenaline from myocardial sympathetic nerve endings possibly responsible for myocardial ischemia and histological damage to the heart  . Novitzky and his group described a significant reduction in myocardial performance associated with a depletion of high-energy phosphates and glycogen reserves  . This may constitutes part of a global energy failure in brain-death owing either to endocrine impairment  or to an oxygen extraction deficiency due to the vasomotor tone dysregulations and microcirculatory maldistributions that occur after the loss of central nervous control  . These findings are further supported by the report from Mertes and co-workers who found an impaired reaction of the heart in brain-dead pigs when challenged by volume expansion leading to a decrease in dP/dt and oxygen delivery  .
A five stage classification of electrocardiographic (ECG) changes and histologic findings in the baboon was described by Novitzky, et al  . Interestingly, the early ECG changes were abolished by vagotomy and the histologic changes were not found if the animals were sympathectomized. In human brain-dead organ donors, atrial or ventricular arrhythmias and various degrees of conduction block have been described  .
Again, the etiology of these arrhythmias is manifold. The sympathetic storm at the onset of brain-death does not just lead to a rise in hemodynamic parameters, but also to an increase in myocardial intra-cellular calcium levels  . This is further aggravated by the appearance of necrotic changes in the conduction tissue of the myocardium  . Hypoperfusion occurring during periods of hypotension might lead to myocardial ischemia and acidosis due to anaerobic metabolism. Hypoxia might also be a consequence of pulmonary dysfunction after neurogenic edema. Uncorrected electrolyte imbalances are another factor, as well as the pro-arrhythmogenic effect of drugs (e.g. catecholamines) in the presence of a very vulnerable conduction system. Last, but not least, hypothermia is another factor affecting the performance of the heart leading to bradycardia and myocardial depression  .
In about 10% of all brain-dead organ donors, a cardiac arrest will occur  . Cardiac fibrillation is more common in adults whereas pediatric donors often show bradycardic episodes and asystole as the terminal cardiac rhythm  . Resuscitation should be carried out in full extent to preserve the transplant able organs until urgent retrieval surgery. Some groups have reported that occurrence of cardiac arrest is not a contraindication for heart donation provided sufficient function is re-established immediately by resuscitation  .
| Endocrinological Complications|| |
Loss of function of the hypothalamic-pituitary axis with failure to secrete the anti-diuretic hormone is a common finding in brain-death  . Typical symptoms of a patient with central diabetes insipidus are shown in [Table - 1].
If not treated adequately, diabetes insipidus will lead to hypovolemia and hypotension resulting in a break-down in organ perfusion and severe electrolyte imbalances (hypernatremia, hypermagnesemia, hypokalemia, hypocalcemia) leading to cardiac arrhythmias, circulatory arrest and graft impairment  . If treatment is delayed, polyuria will result in washout of the renal medullary concentration gradient. Reduced renal responsiveness to vasopressin will necessitate higher doses of vasopressin to stabilize the urinary fluid losses, which in turn increases the possibility of vasopressin-induced ischemic injury to transplantable organs  . However, not all increases in urinary output are related to diabetes insipidus and normal-to increased levels of antidiuretic hormone have been found in donors meeting the clinical criteria of diabetes insipidus  . Hyperglycemia, cold diuresis, preceding diuretic treatment for cerebral edema, the diuretic effect of radiographic contrast material used for angiography or the diuretic reaction to an iatrogenic overhydration should be excluded before treatment with vasopressin is commenced.
Hypothalamic Pituitary Axis
The functional unit, consisting of the hypothalamus, the pituitary gland and the effector glands, is disrupted in brain-death due to the loss of function of the hypothalamic center. The pituitary gland might still be able to maintain its function to a varying degree due to a residual perfusion through extraduraly arising arteries  . Thus, pituitary hormones are found in very variable patterns and levels in brain-dead individuals, but without their diurnal variations or reactivity to external stimuli  . Many reports have investigated the break down of this axis in brain-death and its influence on homeostasis and hemodynamic stability ,,,, . However, deficiencies of pituitary hormones are inconsistent and the available results do not support the routine administration of any of these hormones  .
Novitzky and his group detected reduction in circulating thyroxine levels in the pig and baboon as well as a drop in levels of insulin and cortisol in the baboon, associated with an increasing inability of the tissue to metabolize aerobically , . Further studies on the isolated heart of the pig after brain-death showed a loss of high energy phosphates and deterioration of cardiac function  . Other investigators have also reported similar findings in brain-dead human organ donors and showed significant improvement of hemodynamic parameters after substitution therapy with thyroxine ,,, . However, several controlled studies investigated thyroxine levels in brain-dead human organ donors but were unable to verify a correlation between T3 levels and hemodynamic stability ,,,, . Thus, it remains unclear whether the effect of T3 on stabilization of hemodynamics is in substituting the loss of a physiologic activity or a pharmacologic result. However, introducing an aggressive donor care protocol including hormonal therapy, Wheeldon and co-workers were able to significantly increase the number of transplant able organs  . Further studies will have to clarify whether this success is attributed to the administration of hormones or to the other stabilizing measures included in this protocol.
Hyperglycemia is common in brain-death. However, this is not due to a failure of the pancreatic endocrine function  but seems to be the consequence of a peripheral resistance to insulin, as also known to occur after major trauma. Also, therapeutic measures like catecholamine administration and large volumes of glucose-containing fluids for the correction of diabetes insipid us might contribute to the occurrence of hyperglycemia  . It should be remembered that hyperglycemia induces further fluid losses by osmotic diuresis and can aggravate hypovolemia and electrolyte imbalances.
| Respiratory Complications|| |
Neurogenic lung edema frequently occurs in the management of the brain-dead organ donor. Its onset is sudden and is most frequently seen in brain-dead organ donors in the age-group 13-30 years  . Peripheral vasoconstriction occurring during the sympathetic storm leads to a shift of intravascular volume to the capacitance vessels and an increase in venous return. This results in increased peripheral resistance and a concomitant rise in the left arterial pressure which leads to pulmonary congestion and a rise in hydrostatic pressure and capillary leakage  . Bittner, et al found in a canine brain-death model, a significant decrease in pulmonary vascular resistance and an increase by 10% in pulmonary artery blood flow, leading to an increase in extravascular lung water after brain-death  . Pennefather, et al reported the deleterious effect of fluid loading with crystalloids on lung function, and proposed that fluid substitution should be limited in potential lung donors  .
Many patients suffering from head injury or intracranial bleeding suffer from aspiration, leading to pneumonia. Long treatment periods before brain-death increase the chances for hospital acquired pneumonia. Furthermore, all factors known to complicate respiratory performance in intensive care unit patients like pneumothorax or atelectasis, are prone to appear in brain-dead organ donors.
| Miscellaneous Complications|| |
Due to the loss of the central nervous thermoregulatory center in the hypothalamus and depressed metabolism, hypothermia is likely to be present in all brain-dead organ donors. Also, fluid replacement contributes to the drop in body temperature and hypothermia is often induced deliberately in patients with intracranial pathology for better organ protection and preservation  . However, even in the light of this protective measure, the body temperature should remain above 34° C, firstly to comply with the rules for certification of brain-death and secondly, because hypothermia would further aggravate the destabilization of organ systems. It is known that hypothermia leads to my o car dial depression, cardiac arrhythmias, cardiovascular instability, coagulopathy, hampering the tissue oxygen supply by inducing a left shift of the oxygen dissociation curve, and a decrease in the renal tubular concentration gradient with cold diuresis  .
Bleeding diathesis may be induced by the release of tissue fibrinolytic agents and plasminogen activators from the necrotic brain into the circulation  . This mechanism might persist despite treatment and necessitate urgent organ retrieval when possible; otherwise severe damage to donor organs might occur  .
| Pre-operative Management|| |
Loss of central nervous regulation of the cardiovascular system and deterioration of homeostasis require intensive surveillance including ECG, invasive blood pressure monitoring as well as monitoring of central venous pressure, temperature and urinary output. In cases of severe hemodynamic instability, a pulmonary artery catheter might be useful  . Indications for the placement of a pulmonary artery catheter are listed in [Table - 2]. Frequent arterial blood gas analysis is imperative for the detection of pH shifts, respiratory problems, or electrolyte imbalances.
In general, the therapy protocols are based more often on experience than on results from clinical research. Thus, a wide range of measures are being practiced but essentially, most of them are based on correcting the imbalances found on close monitoring.
Careful volume substitution is necessary to maintain intravascular filling and preload. Endpoints, of therapy should be a heart rate below 100 beats/min, a central venous pressure not higher than 10-12, and a mean arterial pressure higher than 60-70 mm Hg  . However, therapy for hemodynamic stability should be restricted when the systolic blood pressure exceeds 100 to 120 mm Hg, in order to prevent pulmonary edema  . Drop of perfusion pressure is associated with tubular necrosis and kidney graft failure  as well as malfunction of liver grafts  , despite reports of the high tolerance of the liver to hypotensive periods  . Similarly, overhydration is to be avoided as it could cause liver congestion and pulmonary edema , . Also, an early dysfunction of the left ventricle when challenged with a rapid volume infusion has been reported  . No preference is given to crystalloids or colloids. However, Dawidson, et al pointed out the benefits of colloids in facilitating restoration of plasma volume and inducing mild hemodilution with an improved micro-circulation , . In the presence of elevated serum sodium levels due to diabetes insipidus or preceding treatment of cerebral edema, sodium free or low-sodium solutions should be preferred. Fluid should be administered only after prewarming, as this would prevent hypothermia. For the same reason, body warming with a hot air blanket might be necessary.
Although the need for vasopressor support is no longer a contraindication for organ retrieval  , care should be taken to use such drugs only when volume therapy fails to restore a sufficient circulation, and in this case, to prefer those which have the least vasoconstrictor effects  . Dopamine is traditionally used in many centers ,, . However, a dosage of more than 10 jig/kg/ min has been reported to be responsible for the occurrence of acute tubular necrosis and cardiomyopathy in grafts retrieved  . Nakatani and co-workers also reported that the use of dopamine, and not hypotension, led to a reduction of hepatic mitochondrial redox state  . Do-butamine seems to be safe for the treatment of a low cardiac output persisting despite volume expansion up to infusion rates of 15 µg/kg/min  . However, this drug is poorly tolerated if hypovolemia is not corrected or if vasodilatation is predominant  . Adrenaline might be preferable in states of low peripheral resistance due to its inherent alpha-agonist activity. Norepinephrine should be used very carefully and only when all other means fail to preserve sufficient organ perfusion  . However, when peripheral resistance is the problem and further volume substitution is not tolerated for cardiac or pulmonary reasons, alpha-agonists might prove useful in combination with low-dose dopamine for kidney protection.
In all cases of increased inotropic or vasopressor support, a pulmonary artery catheter or if available, trans-esophageal echocardiography, should be used for guidance of therapy. Till now, there is no definitive proof of any endocrine deficiency leading to hemodynamic instability in brain-death cases. However, reports on the clinical success of therapy with cortisol and thyroxine show that, although not recommended for routine treatment  , the use of these hormones is worth considering in hypotensive donors not responding to fluids and catecholamines ,, . Furthermore, the combination of adrenaline and vasopressin as a continuous infusion has proved to be useful in the management of brain-dead donors ,, probably due to synergistic action between these substances  . Wheeldon, et al have reported the use of cardio-pulmonary bypass for stabilization of a brain-dead organ donor leading to the restoration of function of formerly unacceptable heart and kidneys  . However, controlled studies have to investigate the post-transplant function and survival of organs harvested under these conditions before a general use of cardiopulmonary bypass for this indication can be recommended.
Therapy of arrhythmias should follow the same principles as in other patients. However, as the parasympathetic system is impaired in brain-death, atropine is without effect  , thus, brady-arrhythmias need either catecholamine support (which is most often by dopamine or adrenaline) or even a temporary pacemaker. Tachy-arrhythmias are often the first sign of hypovolemia and thus the first step of therapy is to evaluate the volume status of the donor and, if possible, to reduce dysrhythmogenic drugs or substitute them with others. In the presence of hypothermia, bretylium tosylate is regarded as the first-line anti-arrhythmic agent  . Cardiac irritability in hypothermia might be significantly mitigated by decreasing the PaCO 2 by hyperventilation, thus, inducing a mild degree of alkalemia  .
Diabetes insipidus, requiring intervention is present in most brain-dead organ donors  . Major attention has to be paid to substitute fluids and correct electrolyte imbalances. With regard to the occurrence of hypernatremia, hypotonic solutions are preferred such as half-normal saline or dextrose in water, in an amount sufficient to replace urinary losses, meet daily fluid requirements, and maintain the serum sodium at < 155 mmol/L. Frequent monitoring of serum electrolytes is warranted and should be performed every 4-6 hours  . Additional potassium supplementation might be necessary to maintain serum potassium above 3.5 mmol/L. If imbalances get aggravated despite fluid and electrolyte repletion, therapy with controlled vasopressin infusion or desmopressin acetate bolus is necessary. However, the use of vasopressin in brain-dead organ donors is not without danger as this hormone leads to dose-dependent systemic vasoconstriction with an increase in blood-pressure, decrease in cardiac output and coronary and renal blood flow, bradycardia and arrhythmias  . Kidney grafts obtained from donors requiring dopamine and vasopressin showed a higher rate of failure  . The combined use of a vasodilating agent mitigates the hemodynamic response but often necessitates a rise in the inspired oxygen fraction, as intra-pulmonary shunt will increase  . However, the continuous infusion of vasopressin (5 pg/mL) in brain-dead pigs has proved to be safe and efficient  . Thus, it seems preferable to use a continuous vasopressin infusion minimizing the deleterious vasoconstriction and electrolyte shifts at an early point in diabetes insipidus. In the absence of diabetes insipidus. the usual measures to optimize the perfusion and function of the kidneys include avoidance of hypovolemia and possible enhancement of urinary output with diuretics or low-dose dopamine (2-3 µg/kg/min).
The treatment of respiratory failure in brain-dead organ donors is complicated by the danger of impairing cardiac performance by high positive airway pressures  . However, a PaO 2 between 70 and 100 mm Hg is regarded to be sufficient and ventilation should be performed using the lowest possible FiO 2 and PEEP  .
Other Treatment Modalities
Appearance of a coagulopathy might require substitution of clotting factors and transfusion of platelets if their number drops beneath 50 x 10 9 /L. Also the use of fresh frozen plasma might be necessary. The use of epsilon 12-aminocaproic acid is discouraged as it is known to induce micro vascular thrombosis in the donor organs. If hyperglycemia is severe enough leading to electrolyte or acid-base imbalances ox excessive fluid losses, insulin therapy should be established. Continuous intravenous administration is preferred.
Although some centers have reported use of organs from infected donors, this remains a serious threat as the immunosuppressed recipient might not be able to resist such a challenge. Utmost sterility has to be maintained in all procedures involving the donor including catheter, wound and tracheo-bronchial care. Routine checks of sputum, urine and blood cultures as well as daily chest x-rays and serologic screening for transmittable diseases are obligatory  . If an infection is eradicated effectively and no growth is detectable in cultures, organ donation might still take place. Also, care has to be taken that antibiotics with high organ toxicity are not used. For this reason, the prophylactic use of antibiotics as proposed by some centers is discouraged ,, .
| Intra-operative Management|| |
Hemodynamic instability is present in almost all brain-dead organ donors during retrieval surgery. Some donors exhibit marked rises in blood pressure and heart rate in response to painful surgical stimuli like skin incision or sternotomy, elicited by increases of serum levels of endogenous catecholamines  . This hemodynamic response is not seen in all brain-dead organ donors, possibly due to a receptor insufficiency at that point of the deterioration process  . Thus, there is a high variability of the hemodynamic course seen during retrieval surgery  . Duke, et al reported that they were unable to find a correlation between the intra-operative hemodynamic performance of the donor and post-transplant graft failure  . If intra-operative hemodynamic instability occurs, the use of trans-esophageal echocardiography, where available, is encouraged. Monitoring should include heart rate, systemic blood pressure, central venous pressure, temperature and urine output. The frequent measurement of arterial blood gas tensions, acid-base status, electrolytes and blood glucose is mandatory.
The maintenance of adequate tissue oxygenation is also the prime goal of intraoperative management. However, there is no need to exceed the parameters routinely used as end-points for ventilation. Thus, we do not feel the necessity to routinely increase FiO 2 up to 1 as stated in other publications  , and this is even contraindicated in the case of lung or he art-lung transplants.
However, deterioration in pulmonary function might require intensive ventilatory management. Despite the danger of oxygen toxicity, increase of FiO 2 is preferable to measures that are bound to increase the mean airway pressure and thus reducing cardiac output and organ perfusion  . In case of lung procurement, careful repositioning of the endotracheal tube, in accordance with the transplant surgeon, should be made to avoid mucosal injury to the trachea, at the site where anastomosis will be made later. When respiratory support is terminated, after cross-clamping of the aorta, the endotracheal tube should be suctioned and removed.
| Intra-operative Procedures|| |
The question as to whether analgesics should be administered is still unanswered. Although the perception of nociceptive stimuli is non-existent and the use of anesthetics is thus regarded as useless , , surgical stimuli can lead to spinal reflex movements  and reflex sweating  , often leading to anxiety in the operating room personnel. Also, there may be a rise in catecholamine blood levels with the sequelae of vasoconstriction and organ damage  . Beta-blockade ,, as well as nitroglycerin or nitroprusside  were proposed to protect tissue by producing vasodilatation. However, as these hyperdynamic periods are very soon followed by periods of hypotension, the use of a vasodilators might lead to an iatrogenic aggravation of tissue damage. Thus, blockade of spinal nociceptive receptors might interrupt the reflex-circuits and mitigate the pressor response to painful stimuli. However, controlled studies are necessary to evaluate this point and are ongoing presently. Neuromuscular blockade is not just helpful to facilitate the surgical procedure but is also an efficient way of blocking spinal reflex movements. Pancuronium is the drug of choice in the hemodynamically unstable organ donor.
Fluid requirements are often large and should be substituted according to hemodynamic parameters and urinary output. Crystalloids and colloids should both be used to avoid a drop in colloid osmotic pressure and edema of harvested organs. Also, hematocrit should be kept around 30% to ensure adequate oxygen delivery. Guidelines for inotropes are the same as described for the pre-operative course. However, inspite of intensive treatment, most brain-dead organ donors demonstrate a hemodynamic deterioration during the course of the operation ending in cardiovascular collapse. Again, in case cardiac arrest or fibrillation occurs, resuscitation should be initiated until circulation is ensured or procurement of liver and kidneys is accomplished. Pharmacological support includes the administration of heparin (300 U/kg) intravenously before cross clamping, and the use of dopamine (< 3 µg/kg/min) with furosemide or mannitol to achieve diuresis.
When the aorta is cross-clamped and organs are flushed with the preservative solution, support and monitoring may be discontinued to avoid unnecessary stress to the operating-room personnel  . Time of cross-clamping should be registered as the beginning of the cold ischemia period.
| Conclusion|| |
Management of the brain-dead organ donor remains to be a major challenge to the intensivist prior to surgery and to the anesthetist intra-operatively. The treatment of changes occurring in brain-death is further impeded by the scarce information and the small number of controlled studies concerning this subject. Thus, experience often has to compensate for lack of exact treatment rules. Additionally, there is the stress for the intensive care and operation-room team in treating a dead person. However, successful stabilization of the donor and enabling the retrieval of organs in optimal condition is rewarded by healing, increasing life expectancy and quality of life for several patients with terminal organ failure.
| References|| |
|1.||Lucas BA, Vaughn WK, Specs EK, Sanfilippo F. Identification of donor factors predisposing to high discard rates of cadaver kidneys and increased graft loss within one year post-transplantation-SEOPF 1977-1982. South Eastern Organ Procurement Foundation. Transplantation 1987;43:253-8. |
|2.||Wahlers T, Cremer J, Fieguth HG, et al. Donor heart-related variables and early mortality after heart transplantation. J Heart Lung Transplant 1991;10:22-7. [PUBMED] |
|3.||Cabrer C, Manyalich M, Valero R, Garcia Fages LC. Timing used in the different phases of the organ-procurement process. Transplant Proc 1992;24:22-3. |
|4.||Wheeldon DR, Potter CDO, Oduro A, Wallwork J, Large SR. Transforming the "unacceptable" donor: outcomes from the adoption of a standardized donor management technique. J Heart Lung Transplant 1995;14:734-42. |
|5.||Power BM, Van Heerden PV. The physiological changes associated with brain-death-current concepts and implications for treatment of the brain dead organ donor. Anaesth Intensive Care 1995;23:26-36. [PUBMED] |
|6.||Black PM. Brain death. N Engl J Med 1978 ;299:33 8-44,393-401. |
|7.||Rohling R, Schdfer M, Link J, Eyrich K, Smit H, Pichlmayer R. Aufrechterhaltung der Homostase beim Organspender. Anaesthetist 1991;40:29-33. |
|8.||Nygaard CE, Townsend RN, Diamond DL. Organ donor management and organ outcome: a 6-year 25. review from a level I trauma center. J Trauma 1990;30:728-32. |
|9.||Ihle BU. Management of the multi-organ donor. Anaesth Intensive Care 1993;21:710-l.(Abstract) |
|10.||Shivalkar B, Van Loon J, Wieland W, et al. Plets C, Ftameng W. Variable effects of explosive or gradual increase of intracranial pressure on myocardial structure and function. Circulation 1993;87:230-9. |
|11.||Mertes PM, El Abassi K, Jaboin Y, et al. Changes in hemodynamic and metabolic parameters following induced brain-death in the pig. Transplantation 1994;58:414-8. [PUBMED] |
|12.||Pennefather SH, Dark JH, Bullock RE. Haemodynamic responses to surgery in brain-dead organ donors. Anaesthesia 1993;4S: 1034-S. |
|13.||Robertson KM, Hramiak IM, Gelb AW, Endocrine changes and haemodynamic stability after brain-death. Transplant Proc 1989;21:1197-8. |
|14.||Nishimura N, Miyata Y. Cardiovascular change in the terminal stage of disease. Resuscitation 1984,12:175-80. [PUBMED] |
|15.||Robertson KM, Cook DR. Perioperative management of the multi organ donor. Anesth Analg 1990;70:546-56. [PUBMED] [FULLTEXT]|
|16.||Scheinkestel CD, Tuxen DV, Cooper DJ, Butt W. Medical management of the (potential) organ donor. Anaesth Intensive Care 1995;23:51-9. [PUBMED] |
|17.||Neil-Dwyer G, Cruickshank JM. Plasma renin and angiotensin II levels in subarachnoidal haemorrhage. J Neurol Sci 1974;23:463-71. [PUBMED] |
|18.||Pollick C, Cujec B, Parker S, Tator C, Left ventricular wall motion abnormalities in subarachnoid hemorrhage: an echocardiographic study. J Am Coll Cardiol 1988;12:600-5. |
|19.||Fitzgerald RD, Dechtyar I, Tempi E, Fridrich P, Lackner FX. Cardiovascular and catecholamine response to surgery in brain-dead organ donors. Anaesthesia 1995;50:388-92. |
|20.||Mertes PM, Carteaux JP, Jaboin Y, et al. Estimation of myocardial interstitial norepinephrine release after brain-death using cardiac micro-dialysis. Transplantation 1994;57:371-7. [PUBMED] |
|21.||Wicomb WN, Cooper DKC, Lanza RP, Novitzky D, Isaacs S. The effects of braindeath and 24 hours' storage by hypothermic perfusion on donor heart function in the pig. J Thorac Cardiovasc Surg 1986;91;896-909. |
|22.||Novitzky D, Wicomb WN, Cooper DKC, Reichart B. Improved function of stored hearts following hormonal therapy after brain-death in pigs. Transplant Proc 1986; 18:1419-21. |
|23.||Depret J, Teboul J, Benoit G. Mercat A, Richard Globalenergetic failure in braindead patients. Transplantation 1995;60:966-71. |
|24.||Novitzky D, Horak A, Cooper DK, Rose AG. Electrocardiographs and histopathologic changes developing during experimental brain-death in the baboon. Transplant Proc 1989;21:2567-9. [PUBMED] |
|25.||Logigian EL, Ropper AH. Terminal electrocardio-graphic changes in brain-dead patients. Neurology 1985;35:915-8. [PUBMED] |
|26.||Novitzky D, Wicomb WN, Cooper DK, Rose AG, Fraser RC, Barnard CN. Electrocardi©graphic, hemodynamic and endocrine changes during experimental brain-death in the chacma baboon. J Heart Transplant 1984;4:63-9. |
|27.||Ghosh S, Bethune DW, Hardy I, Kneeshaw J, Latimer RD, Oduro A. Management of donors for heart and heart-lung transplantation. Anaesthesia 1990;45:672-5. [PUBMED] |
|28.||Emery RW, Cork RC, Levinson MM, et al. The cardiac donor: a six-year experience. Ann Thorac Surg 19S6;41:356-62. |
|29.||Walsh CK, Krongrad E. Terminal cardiac electric activity in pediatric patients. Am J" Cardiol 1983:51:557-61. |
|30.||Pickett JA, Wheeldon DR, Oduro A. Multiorgan transplantation: donor management. Curr Opin Anaesthesiol 1994;7:80-3. |
|31.||Finkelstein I, Toledo-Pereyra LH, Castellanos J. Physiologic and hormonal changes in experimentally induced brain dead dogs. Transplant Proc 1987;19:4156-8. [PUBMED] |
|32.||Hohenegger M, Vermes M, Mauritz W, Redl G, Sporn P, Eiselsberg P. Serum vasopressin (AVP) levels in polyuric braindead organ donors. Eur Arch Psychiatry Neurol Sci 1990;239:267-9. [PUBMED] |
|33.||Fitzgerald RD, Dechtyar I, Tempi E, Pernerstorfer T. Hackl W, Lackner FX. Endocrine stress reaction to surgery in brain-dead organ donors. Transpl Int 1996;9:102-8. |
|34.||Howlett TA, Keogh AM, Perry L, Touzel R, Rees LH. Anterior and posterior pituitary function in brain-stem-dead donors. A possible role for hormonal replacement therapy. Transplantation 1989;47:828-34. |
|35.||Hall GM, Mashiter K, Lumley J, Robson JG. Hypothalamic-pituitary function in the "brain-dead" patient. Lancet 1980;2:1259. [PUBMED] [FULLTEXT]|
|36.||Schrader H, Krogness K, Aakvaag A, Sortland O, Purvis K. Changes of pituitary hormones in brain-death. Acta Neurochir 1980:52:239-48. |
|37.||Reithmann C, Hallstrom S, Pilz G, Kapsner T, Schlag G, Werdan K. Desensitization of rat cardiomyocyte adenyl cyclase stimulation by plasma of noradrenaline treated patients with septic shock. Circ Shock 1993;41:48-59. |
|38.||Novitzky D, Cooper DK, Reichart B. The value of hormonal therapy in improving organ viability in the transplant donor. Transplant Proc 1987;19:2037-8. [PUBMED] |
|39.||Novitzky D, Cooper DK, Reichart B. Hemodynamic and metabolic responses to hormonal therapy in brain-dead potential organ donors. Transplantation 1987;43:852-4. [PUBMED] |
|40.||Gifford RR, Weaver AS, Burg JE, Romano PJ, Demers LM, Pennock JL. Thyroid hormone levels in heart and kidney cadaver donors. J Heart Transplant 1986;5:249-53. [PUBMED] |
|41.||Novitzky D, Wicomb WN, Cooper DK, Reichart B. Evidence of myocardial and renal functional recovery following hormonal treatment after brain-death. Transplant Proc 1986;18:613-5. |
|42.||Wahlers T, Fieguth HG, Jurmann M, Coppola R, Schdfers HJ, Beer C, Haverich A, Borst HG. Does hormone depletion of organ donors impair myocardial function after cardiac transplantation? Transplant Proc 1988;20:792-4. |
|43.||Macoviak JA, McDougall IR, Bayer MF, Brown M, Tazelaar H, Stinson EB. Significance of thyroid dysfunction in human cardiac allograft procurement. Transplantation 1987;43:824-6. [PUBMED] |
|44.||Masson F, Thicoipe M, Gin H, et al. The endocrine pancreas in brain-dead donors. A prospective study in 25 patients. Transplantation 1993;56:363-7. |
|45.||Soifer B, Gelb AW. The multiple organ donor: identification and management. Ann Intern Med 1989;110:814-23. [PUBMED] |
|46.||Cooper DK, Novitzky D, Wicomb WN. The pathophysiological effects of brain-death on potential donor organs, with particular reference to the heart. Ann Coll Surg Engl 1989;71:261-6. |
|47.||Bittner HB, Kendall SW, Chen EP, Craig D, Van Trigt P. The effects of brain-death on cardiopulmonary hemodynamics and pulmonary blood flow characteristics. Chest 1995;108:1358-63. [PUBMED] [FULLTEXT]|
|48.||Pennefather SH, Bullock RE, Dark JH. The effect of fluid therapy on alveolar arterial oxygen gradient in brain-dead organ donors. Transplantation 1993;56:1418-22. [PUBMED] |
|49.||Illievich UM, Bacher A, Spiss CK. Active cooling during anesthesia and critical care. J Neurosurg Anesthesiol 1996;8:78-82. [PUBMED] [FULLTEXT]|
|50.||Reuler JB. Hypothermia: pathophysiology, clinical settings, and management. Ann Intern Med 1978;89:519-27. [PUBMED] |
|51.||Miner ME, Kaufman HH, Graham SH, Haar FH, Gildenberg PL. Disseminated intravascular coagulation fibrinolytic syndrome following head injury in children: frequency and prognostic implications. J Pediatr 1982;100:687-91. [PUBMED] |
|52.||Carroll RN, Chisholm GD, Shackman R. Factors influencing early function of cadaver renal transplants. Lancet 1969;2:551-2. [PUBMED] |
|53.||Busuttil RW, Goldstein LI, Danovitch GM, Ament ME, Memsic LD. Liver transplantation today. Ann Intern Med 1986;104:377-89. [PUBMED] |
|54.||Lin H, Okamoto R, Yamamoto Y, et al. Hepatic tolerance to hypotension as assessed by the changes in arterial ketone body ratio in the state of brain-death. Transplantation 1989;47:444-8. [PUBMED] |
|55.||Dawidson I, Berglin E, Brynger H, Rcisch J. Intravascular volumes and colloid dynamics in relation to fluid management in living related kidney donor's and recipients. Crit Care Med 1987;15:631-6. |
|56.||Dawidson I, Berglin E, Brynger H. Perioperative fluid regimen, blood and plasma volumes and colloid changes in living-related donors. Transplant Proc 1984;16:18-9. |
|57.||Trento A, Hardesty RL, Griffith BP, Kormos RL, Bahnson HT. Early function of cardiac homografts: relationship to hemodynamics in the donor and length of the ischemic period. Circulation 1986;74(III):77-9. |
|58.||Klintmalm GB. The liver donor: special considerations. Transplant Proc 1988;20:911. |
|59.||HirschI MM, Laggner AN. Medizinische Be-treuung von Organspen dern. In: Lenz K, Laggner AN, eds. Transplantation. Intensivmedizinisches Seminar Vol 8. Wien: Springer-Veriag 1995:13-20. |
|60.||Ballester M, Obrador D, Abadal L, et al. Dopamine treatment of locally procured donor hearts: relevance on postoperative cardiac histology and function. Int J Cardiol 1989;22:37-42. [PUBMED] |
|61.||Nakatani T, Ishikawa Y, Kobayashi K, Ozawa K. Hepatic mitochondrial redox state in hypotensive brain-dead patients and an effect of dopamine administration. Intensive Care Med 1991; 17:103-7. [PUBMED] |
|62.||Link J, Rohling R, Gramm HJ. Preservation of homeostasin following the onset of braindeath. Anaesthesiol Reanimatol 1990;15:249-60. |
|63.||Randell TT, Hockerstedt KAV. Triiodothyronine treatment in brain-dead multiorgan donors-a controlled study. Transplantation 1992;54:736-8. |
|64.||Kinoshita Y, Yahata K, Yoshioka T, Onishi S, Sugimoto T. Long-term renal preservation after brain-death maintained with vasopressin and epinephrine. Transpl Int 1990;3:15-8. [PUBMED] |
|65.||Yoshioka T, Sugimato H, Venishi M, et al. Prolonged hemodynamic maintenance by the combined administration of vasopressin and epinephrine in brain-death: a clinical study. Neuro-surgery 1986;18:565-7. |
|66.||Iwai A, Sakano T, Uenishi M, Sugimoto H, Yoshioka T, Sugimoto T. Effects of vasopressin and catecholamines on the maintainance of circulatory stability in brain-dead patients. Transplantation 1989;48:613-7. [PUBMED] |
|67.||Cowley AW Jr, Monos E, Guyton AC. Interaction of vasopressin and the baroreceptor reflex system in the regulation of arterial blood pressure in the dog. Circ Res 1974;34:505-14. [PUBMED] |
|68.||Whceldon DR, Potter CD, Dunning J, et al. Haemodynamic correction in multiorgan donation. Lancet 1992;339:1175. |
|69.||Vaghadia H. Atropine resistance in braindead organ donors. Anesthesiology 1986;65:711-2. [PUBMED] |
|70.||Elenbaas RM, Mattson K, Cole H, Steele M, Ryan J, Robinson W. Bretylium in hypothermia-induced ventricular fibrillation in dogs. Ann Emerg Med 1984;13:994-9. [PUBMED] [FULLTEXT]|
|71.||Kroncke GM, Nichols RD, Mendenhall JT, Myerowitz PD, Starling JR. Ectothermic philosophy of acid-base balance to prevent fibrillation during hypothermia. Arch Surg 19S6;121:303-4. |
|72.||Hofbauer KG, Studer W, Wah SC, Michel JB, Wood JM, Stalder R. The significance of vasopressin as a pressor agent. J Cardiovasc Pharmacol 1984;6 Suppl 2:S429-38. |
|73.||Schneider A, Toledo-Pereyra LH, Zeichner WD, Allaben R, Whitten J. Effect of dopamine and pitressin on kidneys procured and harvested for transplantation. Transplantation 1983;36:110-1. [PUBMED] |
|74.||Mols P, Hallemans R, Van Kuyk M, et al. Hemodynamic effects of vasopressin, alone and in combination with nitroprusside, in patients with liver cirrhosis and portal hypertension. Ann Surg 1984;199:176-81. [PUBMED] [FULLTEXT]|
|75.||Blaine EM, Tallman RD Jr, Frolicher D, Jordan MA, Bluth LL, Howie MB. Vasopressin supplementation in a porcine model of brain-dead potential organ donors. Transplantation 1984;38:459-64. |
|76.||Dormsky PM, Whitcomb ME. The effect of PEEPon cardiac output. Chest 1983;84:210-6. |
|77.||Odom NJ. Organ donation. Management of the multiorgan donor. BMJ 1990;300:1571-3. |
|78.||D'Amico TA, Meyers CH, Koutlas TC, et a). Desensitization of myocardial beta-adrenergic receptors and deterioration of left ventricular function after brain-death. J Thorac Cardiovasc Surg 1995;110:746-51. |
|79.||Duke PK, Ramsay MA, Paulsen AW, et al. Intraoperative hemodynamic heterogeneity of brain dead organ donors. Transplant Proc 1991;23:2485-6. [PUBMED] |
|80.||Prager MC. Care of organ donors. In: Lebowitz PW, ed. International Anesthesiology Clinics Vol 29 No 3. Boston: Little, Brown and Co. 1991:1-16. |
|81.||Salter DR, Dyke CM. Cardiopulmonary dysfunction after brain death. In: Fabian JA, ed. Anesthesia for organ transplantation. Philadelphia: J.B. Lippincott Co. 1992:81-94. |
|82.||Walpoth B, Barbalat F, Vitus L, Fathi N, Faidutti B, Jardetzki N, Jamieson S. Detrimental effect of endogenous and/or exogenous catecholamine stimualtion on ischemic myocardial tolerance and energistics. J Heart Transplant 1985;4:606. |
|83.||Fiser DH, Jimenez JF, Wrape V, Woody R. Diabetes insipidus in children with brain-death. Crit Care Med 1987;15:551-3. [PUBMED] |
Robert D Fitzgerald
Department of Anesthesia and General Intensive Care, University of Vienna Medical School, Wehringer Gurtel
[Table - 1], [Table - 2]
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