Objectives: Optimal care of potential donors can lead to successful transplantation. Hemodynamic insta-bility is a common complication in deceased potential donors. The most common underlying causes are hormonal and electrolyte disturbances as well as a hyperinflammatory state, which is rooted in activation of the cytokine cascade. In this study, our aim was to evaluate the efficacy of methylprednisolone injection, an agent introduced for inflammation suppression to achieve more stability in cases of hemodynamic disturbances.
Materials and Methods: This study covered the period from April 2016 to June 2017 and included 45 randomly selected hemodynamically unstable brain-dead cases (mean arterial pressure < 60 mm Hg). For these cases, primary management included trying to achieve stability; however, after many hours, we experienced hemodynamic instability again. Because of no other correctable methods, we decided to use methylpred-nisolone injection. The potential deceased donors received a total of 1 g methylprednisolone in two 500-mg divided doses after transfer to the organ pro-curement unit.
Results: Of 45 patients, 26 were male (58%), and the mean age of patients was 33 years. The most common causes of brain death were trauma (33%) and cerebro-vascular accident (22%). Systolic and diastolic blood pressures increased significantly after methylpred-nisolone use. We observed no significant dif-ferences in pulse rate. In addition, methylprednisolone could correct pH from 7.33 ± 0.11 to 7.38 ± 0.12 (P = .007).
Conclusions: Use of methylprednisolone in hemo-dynamically unstable deceased donors could allow better management of these cases. Because there are various factors such as infusion of vasopressor drugs or fluid therapy that could affect the hemodynamic status of these cases, future studies with larger sample sizes are recommended to control these confounding factors.
Key words : Blood pressure, Deceased donors, Hemodynamic instability, Inflammation
Transplantation is the only option for many patients with end-stage organ failure, and wait list mortality is a real issue.1 Optimal care of potential donors could result in successful transplantation, decrease the number of donors lost, and increase the number of organs retrieved per potential donor.1-3
Hemodynamic instability is one of the most common complications of brain death. The sym-pathetic storm and the subsequent hemodynamic instability after brain death may lead to hypo-perfusion and ischemia in various organs, conse-quently activating the cytokine system. This process could lead to negative effects on transplant outcomes of major organs such as heart, liver, and kidneys.4,5 Therefore, the goals in management of hemodynamic instability include maintenance of blood pressure with minimal use of inotropes, optimizing fluid management, and maintenance of organ perfusion.6
Methylprednisolone is an effective agent in suppressing inflammatory chemicals, such as monocyte chemotactic protein 1, interleukin (IL) 2, IL-6, tumor necrosis factor alpha (TNF-α), and inducible protein 1, and increasing steroid plasma levels. Previous clinical trials on the effects of methylprednisolone on hemodynamic instability are limited. In this study, our aim was to evaluate the efficacy of methylprednisolone injection in achieving more stability in hemodynamic disturbances in deceased donors.7
Materials and Methods
Our study included 45 randomly selected brain-dead potential donors who were seen over a 14-month period (from April 2016 to June 2017). Inclusion criteria were brain death of different causes and hemodynamic instability (mean arterial pressure < 60 mm Hg). Brain death was diagnosed clinically (coma, absences of brainstem reflexes, apnea test) and then confirmed with electroencephalography and transcranial Doppler sonogram.
Hemodynamic stability was assessed by con-tinuous, complete cardiac monitoring and by measurement of systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels. All patients received endotracheal intubation and were ventilated, with respiratory systems monitored using pulse oximetry and arterial blood-gas sampling. Electrolytes were measured. Proper hydration procedures were performed, and inotropes were administered to maintain mean arterial pressure > 60 mm Hg and urine output > 1 mL/kg/h.8
For these cases, we performed primary manage-ment and tried to achieve stability; however, after many hours, we experienced hemodynamic instability again. We found no other correctable method and finally decided to use methylprednisolone injection. Potential deceased donors received a total of 1 g methylprednisolone in two 500-mg divided doses after transfer to the organ procurement unit of the Massih Daneshvari Hospital (Tehran, Iran).
Vital signs, arterial blood-gas indexes, and electrolyte levels were measured before and 1 hour after methylprednisolone injection.
Before start of study, the ethics committee of the institution approved this study; the protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration. Written informed consent was obtained from all donor families for organ donation and for research purposes. Paired sample t tests were used for comparisons of measurements before and after treatment.
Of 45 total patients, 26 were male (58%), and the mean age was 33 years. The most common causes of brain death were trauma (33%) and cerebrovascular accident (22%). We found that SBP and DBP increased significantly after methylprednisolone use (mean SBP from 82 to 94 mm Hg; P = .021 and mean DBP from 51 to 62 mm Hg; P = .04). There were no significant dif-ferences in pulse rate. Although the mean concen-tration of potassium and sodium after treatment increased to 4.1 ± 0.9 mEq/L and 144 ± 6.2 mEq/L, they were not statistically significant (P = .072 and P = .3). In addition, methylprednisolone corrected pH from 7.33 ± 0.11 to 7.38 ± 0.12 (P = .007).
In this study, use of methylprednisolone had a significant effect on increasing mean arterial pressure and achieving hemodynamic stability in potential deceased donors. We found that SBP and DBP increased significantly after methylprednisolone injection. However, there has been previous conflicting evidence to support the routine use of corticosteroids in the management of organ donors, and there is no absolute guideline for types of corticosteroid use and optimum dosage.9
Different dosages have been used in previous studies.10 Nevertheless, the most recommended dose has been 15 mg/kg.1,11,12 In our study, treatment with 2 divided doses of 500 mg methylprednisolone resulted in a rise of SBP from 61 to 72 mm Hg independent of inotrope dosage. We observed no significant differences in pulse rate, which is in agreement with previous studies. For example, Novitzky and associates showed that use of hormonal therapy resulted in hemodynamic stability and reduced inotrope usage.13 In a study from Nicolas-Robin and colleagues, corticosteroid supplementation enhanced the systemic hemodynamic stability and decreased the inotrope dose regardless of the donor’s pathophysiologic corticosteroid status.14 Regarding the effects of methylprednisolone on graft function, some investigations of kidney allografts from deceased donors showed no difference in graft function.15,16 Another study by Kotsch and associates showed improved graft function after methylprednisolone administration.7 However, Dhar and associates found that corticosteroid administration had no significant influence on vasopressor weaning and resulted in no difference in ejection fraction or difference in graft and patient survival.17
Another finding in our study was that methylpre-dnisolone could correct pH from 7.33 to 7.38 without bicarbonate requirement. This is in agreement with Novitzky and associates, who showed that methylprednisolone treatment could decrease the bicarbonate requirement and could lead to correction of metabolic acidosis.13
Possible mechanisms of action
Brain death has been shown to result in increased blood levels of several cytokines, including TNF-α, IL-6, IL-8, IL-1b, and IL-2R.7,18 Glucocorticoids have been shown to decrease inflammatory responses caused by brain death. In the study from Kotsch and associates,7 after methylprednisolone treatment, steroid plasma levels were significantly higher and significant decreases in soluble interleukins, mo-nocyte chemotactic protein 1, IL-2, IL-6, TNF-α, and inducible protein 10 were observed. Corticosteroid supplementation is also beneficial for adrenal insufficiency caused by brain death and endogenous corticosteroid resistance.14,19 Sprung and colleagues20 showed that hydrocortisone reduces the need for vasopressors. These characteristics could explain the benefits of corticosteroids in treating hemodynamic instability in deceased donors.20
There are several limitations in our study. For example, follow-up of organ donation and adverse effects of methylprednisolone on organs could not be observed. Future studies with bigger sample sizes and more cases and attempts to form an equalized control group are recommended.
The use of methylprednisolone in hemodynamically unstable deceased donors could result in better management of these cases. Because of the various factors, such as infusion of vasopressor drugs or fluid therapy, that could have affected the hemodynamic status of these cases, future studies with larger sample sizes are recommended to control these confounding factors.
Volume : 17
Issue : 1
Pages : 257 - 259
DOI : 10.6002/ect.MESOT2018.P113
From the Organ Procurement Unit (OPU), Lung Transplantation Research Center
(LTRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD),
Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Meysam Mojtabaee, Organ Procurement Unit (OPU), Lung Transplantation Research Center (LTRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences (SBMU), Darabad, Niavaran, Tehran, Iran 19569-44413
Phone: +98 2127122103