A 2013 meta-analysis evaluates the efficacy of interventions used to stabilize hemodynamics in brain-dead donors or to improve organ function and outcomes of transplantation. Of the interventions evaluated, a total of two studies (n= 121) included in the analysis evaluated the use of desmopressin, a synthetic form of vasopressin. In one study, a total of 97 brain-dead donors received desmopressin as 1 mcg bolus every 2 hours if they were diagnosed as having diabetes insipidus with a diuresis of more than 300 mL/h. Desmopressin was discontinued 2 hours before organ harvesting. Patients in the control group received no desmopressin. No significant differences were found between the two groups of brain-dead donors, except for final diuresis, which was lower in the desmopressin group than the control group (0.38 L/h vs. 0.70 L/h; p= 0.0001). Hemodialysis requirements and serum creatinine concentrations also did not differ between the two groups 15 days after transplantation, and long-term graft survival was similar in both groups (88% vs. 87%). [1], [2]
In the other study, a total of 24 brain-dead organ donors were assessed based on the use of a control or desmopressin. Initially, in patients who had a central venous pressure (CPV) <8 mm Hg received lactated Ringer’s solution until a CVP of 8 mmHg was attained, and dextrose 5% was administered at 80 mL/hour. Patients in whom the urine output exceeded 3 mL/kg/hr for 2 successive hours were treated with desmopressin 2 mg IV. The treatment was repeated if the urine output again exceeded 3 mL/kg/hr for 2 successive hours. Patients received additional treatment with oxygen and dopamine to maintain a mean arterial pressure (MAP) of 65 to 85 mmHg. When patients were hemodynamically stable at the goal MAP, patients were randomized to receive either a 300 microunit/kg/min infusion of arginine vasopressin (AVP) or a saline infusion. Use of AVP significantly decreased plasma hyperosmolality, increased blood pressure, decreased inotrope use, and maintained cardiac output. The control group, however, experienced no significant changes in blood pressure, cardiac output, or inotrope infusion rate. Overall, early organ function was similar between the two groups. [1], [2], [3]
Pooled data from these two studies within the meta-analysis found no benefit for desmopressin on early graft function of kidney transplants (relative risk 0.97; 95% confidence interval 0.85 to 1.10). While the use of desmopressin was not associated with better kidney graft outcomes, its safe and effective use for limiting the harmful effects of profuse polyuria, decreasing the need for large-volume infusions, and preventing hemodynamic collapse, were deemed as potential benefits for using desmopressin in the organ donor setting. [1]
A 2019 review article assessed the benefits of using hormonal therapy, including vasopressin, in brain-dead donors to optimize recipient outcomes. Hypotension and diabetes insipidus, conditions that commonly occur in brain-dead patients, can lead to donor instability due to inadequate organ perfusion. Diabetes insipidus in these donors can be managed by either vasopressin or the synthetic vasopressin analog (1-d-amino-8-d-arginine vasopressin [DDAVP]), which is also referred to as desmopressin. DDAVP is the preferred agent for treating diabetes insipidus in the absence of hypotension due to being highly selective for the V2 renal receptors; it may be administered as an intravenous (IV) bolus of 2 to 6 mcg every 6 to 8 hours or as needed. There is some concern that DDAVP at lower doses (<0.3 mcg/kg) may be procoagulant and detrimental to pancreatic and renal graft transplant function, however, reports on effects on transplant outcomes are inconsistent. [4]
Vasopressin may be used for the treatment of both diabetes insipidus and hypotension due to its activity at both the V2 renal receptors and the V1 receptors on vascular smooth muscle; it must be administered via IV infusion due to its shorter half-life than DDAVP (10 to 35 min). The typically used vasopressin dose range is 0.5 to 2.4 units per hour, titrated to blood pressure and urine output. Doses up to 4 units per hour have been suggested in some guidelines, but there is concern that doses greater than 0.04 units per minute could cause potentially deleterious vasoconstriction of renal, mesenteric, pulmonary, and coronary vasculature. [4]
There is a lack of well-studied comparisons between the use of different vasoactive agents in organ donors. One retrospective registry analysis study in the United States found vasopressin was associated with a higher number of organs received per donor. Norepinephrine is the most commonly used vasoactive agent used in Australia and New Zealand for blood pressure management in donors. In conclusion, the authors of the review suggest vasopressin as the preferred agent if donors have both diabetes insipidus and hypotension. Desmopressin may also be used concurrently with vasopressin if the vasopressin dose required for blood pressure support is not sufficient to also control diabetes insipidus. [4], [5]
According to a 2019 guideline published by the Intensive Care Society of Ireland, vasopressin is recommended first-line for the vasodilatory shock state associated with brain death at a dose of 0.5 to 2.4 IU/h. This low dose of vasopressin is suggested to aid restoration of vascular tone and treat diabetes insipidus via an antidiuretic effect in the distal nephron. The guidelines also provide detailed management of diabetes insipidus in the setting of organ donation. Following replacement of ongoing fluid losses and any existing fluid deficit with hypotonic fluid, if urine output is > 3 mL/kg/h, an infusion of IV vasopressin and/or intermittent subcutaneous or IV DDAVP is recommended. If vasopressor support is required, IV vasopressin should be infused at a rate of 0.5-2.4 IU/h. However, vasopressin alone often is not adequate to control diuresis, and DDAVP should be given as soon as diabetes insipidus is suspected. DDAVP is an analog of arginine vasopressin with enhanced antidiuretic potency, negligible vasopressor activity, and a prolonged half-life compared to vasopressin. The recommended dose of DDAVP in adults is 1-2 mcg subcutaneously or IV followed by 1-2 mcg subcutaneously or IV as required to achieve a urine output <3 mL/kg/h. Overall, hemodynamic goals should include a blood pressure maintained at a MAP of 60-70 mmHg, central venous pressure of 6-10 mmHg, and urine output of 1-3 mL/kg/h. [6]
Another review published in 2016 describing the management of organ donors after brain death suggests that in donors with diabetes insipidus who are at high risk of developing hypovolemia or continue to be hypotensive despite crystalloid repletion, vasopressin can be initiated with a bolus of 1 unit followed by a continuous infusion of 0.5-4 units/hr. Desmopressin, a synthetic vasopressin analog, has a longer duration of action and a decreased vasoconstrictor effect compared to vasopressin. It is recommended to be given at a rate of 0.5-2.0 mcg/hr every 2-3 hours adjusted to achieve a urine output goal of 1-3 mL/kg/hr. [7]
A randomized controlled trial published in 1998 evaluated use of desmopressin in brain-dead donors and analyzed early and long-term graft function in kidney recipients. Brain-dead donors were randomized to receive control (n= 48) or desmopressin (n= 49) administered as an intravenous bolus of 1 mcg every 2 hours for diuresis greater than 300 mL/h. Overall, no significant differences were noted between the control and desmopressin groups of brain-dead donors, except for final diuresis, which was lower in the desmopressin group (0.38 ± 0.30 vs. 0.70 ± 0.54 mL/h, p<0.05). Of 174 kidney recipients analyzed (89 in the control group and 86 in the desmopressin group), the rate of hemodialysis during the early post-transplantation was not significantly different between the two groups (20% vs. 23%) nor was the serum creatinine concentrations over a 15-day period post-transplantation. Long-term results of kidney transplantation between the two groups did not differ. It was demonstrated that desmopressin can be safely administered in brain-dead donors to limit the deleterious consequences of diabetes insipidus, but the clinical significance may be limited. Limited information could be obtained from this study, as it is only available in abstract form. [8]