**6.1 Medical consultant system**

Among brain-dead donors, only 20% meet the standard donor criteria for all medical conditions. Therefore, to solve the shortage of donors, it is important to make it possible to transplant marginal donor organs. In other words, the purpose of donor management is not simply to stabilize the hemodynamics of the donor until the surgical resection, but to enable the donation of as many organs as possible, improve the organ function of the marginal organs, and improve the organ function after transplantation. This allows many transplant recipients to benefit from organ transplantation. At the same time, it fulfills the wishes of donors and their families, who want to donate as many organs as possible. However, if the recipient dies early after the transplant by forcing the transplant, the donor family feels that they have lost their family once again. Do not forget that the donor family will feel guilty if the recipient dies soon after transplantation. In other words, eliminating primary graft failure (PGF) is important not only for the recipient but also for the donor and their family.

In Japan, since November 2002, medical consultants (MCs) have introduced the system [10] and have been conducting meticulous evaluation and management of donors. After the first determination of brain death, the MCs are dispatched to the

*Heart Transplantation and Mechanical Circulatory Support in Japan – Past, Current and Future… DOI: http://dx.doi.org/10.5772/intechopen.113730*

donor hospital, evaluate the donor, and manage the donor from the second determination of brain death. Since the basics of donor management are respiratory and circulatory management, donor management is performed by heart and lung transplant doctors, but organ evaluation may be requested by the MC of each organ as necessary. At the beginning of 2002, the number of MCs was small, but now JOT entrusts MCs to 2 persons from each heart transplant facility, 3 persons from each lung transplant facility, and several transplant doctors for other organ transplants.

After obtaining the consent of the donor family to donate brain-dead organs, the MCs received the first call before the first brain-death determination began and arrived at the donor hospital. If the donor's hemodynamics are unstable, JOT coordinators consult with the MCs to stabilize it, and if requested by the donor hospital, MCs attend an apnea test and support hemodynamics management.

#### **6.2 Donor management**

#### *6.2.1 Management of hemodynamics*

There is no drug therapy that restores the organ viability and function in a short period of time, and it is extremely difficult to restore function after the organ has been removed. Improving organ function and restoring organ function are the mainstays of donor management. Again, why the hemodynamic/respiratory condition is poor should be evaluated first, and the treatment should be determined based on the evaluation results. Drugs that increase peripheral vascular resistance, especially noradrenaline, reduce blood flow in abdominal organs and worsen perfusion of organ preservation solutions, so the dose should be reduced as much as possible. Preservation of cardiac function is achieved by adjusting preload and afterload, administering anti-diuretic hormone (ADH) (details described later), and keeping the dose of catecholamine at the minimum maintenance dose (DOA 10 μg/Kg/min or less as much as possible).

The target values for hemodynamics are (1) systolic blood pressure of 90 mmHg or more, (2) central venous pressure (CVP) of 6–10 mmHg, and (3) hourly urine output of 100 ml/hr. (or 0.5–3 ml/kg/hr).) above, (4) Heart rate 80-120 beats/minute.

### *6.2.2 ADH replacement therapy*

When the ADH blood concentration decreases, (1) diabetes insipidus, (2) a decrease in vascular tone, and (3) a decrease in the affinity of myocardial β-adrenergic receptors, resulting in unstable hemodynamics. Although there are reports that ADH is supplemented only in patients with diabetes insipidus, ADH should be administered even in cases of low urine volume in order to improve (2) and (3). Similar to the administration of ADH after open-heart surgery or in shock during sepsis, the administration of ADH improves hemodynamics, which in turn improves renal function, which often results in an increase in urine output.

Regards to the administration method of ADH, there are reports that it is administered to the bolus by intranasal administration or intramuscular injection, hemodynamics are well stabilized by initial intravenous administration of 0.02 U/ Kg (or 1 U) as a bolus followed by continuous intravenous administration (0.01- 0.2 U/Kg/hr. or 0.5-1 U/hr). If hemodynamics is stabilized after administration of ADH while maintaining systemic blood pressure of 90 mmHg or more and urine output of approximately 1-2 ml/Kg.hr., r catecholamines are tapered in the order

of noradrenaline and adrenaline. As endogenous and exogenous adrenaline levels decrease, the heart rate stabilizes at around 90-120 beats/minute. If the urine output drops sharply after starting ADH, the dose of ADH is reduced. There are many reports of discontinuing ADH before surgical resection, but discontinuation of ADH may lead to a sudden increase in urine output or decreased adrenaline sensitivity in the myocardium and blood vessels, resulting in intraoperative hemodynamic instability. Therefore, ADH administration is discontinued just before heparinization.

#### *6.2.3 Respiratory management*

Acute lung injury (ALI) and adult respiratory distress syndrome (ARDS) occur due to the occurrence of various systemic inflammatory reactions before and after brain death, and the sympathetic nervous system is overexcited (sympathetic/autonomic storm) in 15. -20% of brain-dead persons. In addition, due to the denervation, atelectasis easily develops, and pneumonia is likely to occur unless endotracheal suction is carefully performed. In addition, diabetes insipidus can lead to pulmonary edema when excessive hydration leads to a decrease in serum oncotic pressure.

Ventilator settings were made to maintain partial pressure of arterial oxygen (PaO2) of 100 mmHg or more by setting a low fraction of inspiratory oxygen (FiO2) and positive end-expiratory pressure (PEEP) of 5 cmH2O or to maintain PaO2 of 70-100 mmHg or more, SaO2 of 95% or more, PaCO2 at 30-35 mmHg and pH of 7.35-7.45 by setting tidal volume of 10-12 ml/Kg and maximum airway pressure of 30 mmHg or less. Keeping oxygen concentration, tidal volume, and PEEP as low as possible reduces the inflammatory response in the lung and is thought to improve lung function after transplantation.

Because airway neural reflexes (cough reflex, etc.) are lost, regular repositioning and airway suctioning are important in preventing pulmonary infections and atelectasis. Atelectasis is especially likely to occur in the back of the body. However, in brain death, the cardiac and vascular reflexes are lost, so postural changes and endotracheal suctioning (fluctuations in airway pressure and blood return to the lungs) can easily cause blood pressure to fluctuate, making airway management difficult. Hemodynamic instability is even more difficult to manage, so replenishing ADH and stabilizing hemodynamics are also important in terms of respiratory management.

If the cough reflex is lost, deep sputum aspiration becomes insufficient, so bronchoscopic tracheal/endobronchial aspiration is important. Taking regular chest X-rays (generally every 6-8 hours), observing the progress of atelectasis and pneumonia, and repeating endotracheal aspiration not only improves the condition of the transplanted lung but also reduces the size of the lung. Increased availability.

## *6.2.4 Correction of electrolytes, hematocrit, and blood sugar*

It is well known that hypernatremia adversely affects liver and pancreatic function. In the heart, Hoefer et al. [11] reported that the 1-year survival rate of heart transplant recipients from donors with Na < 130 mEq/l and ≥ 170 mEq/l was significantly lower than those from donors within the normal range. and normalizing Na is important. Na-free (or low-Na) transfusion is often performed to correct hypernatremia, but this alone is not sufficient, and it is important to achieve natriuresis by correcting ADH. Correct the serum Na level to a target of 135-150 mEq/l.

*Heart Transplantation and Mechanical Circulatory Support in Japan – Past, Current and Future… DOI: http://dx.doi.org/10.5772/intechopen.113730*

When diabetes insipidus occurs and the circulating blood volume decreases, a large amount of transfusion is required, the blood is diluted, and hypokalemia and anemia are likely to occur. First, while treating diabetes insipidus with ADH, it is important to periodically measure the serum K level and replenish K through the central route. Correct the serum K value to about 3.8-4.5 mEq/l. If short-term correction is unavoidable, it may be necessary to administer KCl in a double dilution (0.2 mEq/ kg/hr) with a syringe, but this should be administered with careful monitoring. Generally, as diabetes insipidus improves, the serum K value often normalizes. Since anemia impairs organ function, blood transfusion should be performed so that the hematocrit is 30% or higher.

When brain death occurs, the adrenaline concentration in the blood increases, and various inflammatory reactions occur, making it easy to develop hyperglycemia. Suspect hyperglycemia if urine output does not optimize even after correcting ADH. Treatment is first with non-glucose transfusions, and if the condition is still not optimized, continuous intravenous administration of insulin (regular insulin 0.5-1.0 IU/ hr). Blood glucose is corrected to target 120-180 mg/dl.

#### *6.2.5 Body temperature control*

When brain death occurs, body temperature cannot be regulated, so it is easy to fall into hypothermia. This is particularly noticeable after hypothermia of the brain or when a large amount of fluid is infused due to diabetes insipidus. Compensate for 35.5-36.5°C.

#### *6.2.6 Control of infectious diseases*

Long-term brain death can easily lead to pneumonia from atelectasis and infections from bedsores and various catheters. Therefore, in addition to endotracheal suctioning, postural changes to prevent bedsores and care for various catheters, wounds, and bedsores are important. If infection is suspected, ask for bacteriological examination (preferably culture) and administer sensitive antibiotics. Cultivation takes time, so smear examination (a Gram stain is sufficient) is helpful. Antibiotics are started 1 hour before leaving the ward to increase blood levels of antibiotics immediately before skin incision for excisional surgery.

As a result of such careful donor evaluation and management, the average number of organs donated from one donor is 5, which is more than in Europe and the United States (average of 3₋4 organs). It seems that the wish of the donor family is also fulfilled.
