Key words : Brain death, Drug overdose, Organ donation, Poisoned donors, Recipient survival rate

Introduction

A toxin is a substance that can lead to damage or death of an organism, and poisoning is an event in which the body absorbs substances through the mouth, respiration, mucosa, and arteries, which can consequently result in a series of side effects. Poisoning complications can cause severe damage or complications.¹ In 2019, the 55 poison control centers in the United States provided telephone guidance for over 2.1 million human poison exposures, with 643 poison exposures reported per 100 000 population.² Studies conducted in different Iran cities, such as Tehran, Mashhad, and Babol, have shown the highest numbers of drug poisonings.^3-6

Brain death is determined after a patient has sustained some form of a catastrophic neurologic injury that results in an irreversible loss of cerebral and brain stem function. One of the definitive criteria for determining death is brain death.^7-9 Brain death is determined with the use of clinical tests and instrumental confirmatory tests.¹⁰ Causes of brain death include car accidents, severe head injuries, internal cerebral hemorrhages, strokes, and severe poisoning. Some drugs and substances can mimic brain death, such as snake envenomation, baclofen, tricyclic antidepressants, bupropion, alcohol, antiepileptic agents, barbiturates, antidysrhythmics, and organophosphates.^11-13

Brain death determination in poisoned patients requires consultation by a clinical toxicologist to exclude the influence of neurotoxic xenobiotics on the central nervous system.¹⁰ Brain death guidelines should be used with caution in patients with drug intoxication.¹³ According to the Ministry of Health, the average number of brain deaths in Iran ranges from 5000 to 6000 people/year.¹⁴ The incidence of brain death has increased in the United States; from 2012 to 2016, there were 69 735 brain death in the United States.¹⁵

Many countries have organ transplant programs, and the demand for transplant is increasing rapidly. Statistics have revealed that the number of organ transplants in the United States and Europe has increased significantly over the past 3 decades.¹⁶ Organ donation from a living donor, mostly for kidney transplant, is now performed worldwide. However, because of limited organ donations from living donors and the growing demand for organ transplant resulting from increases in population, brain dead donors have been used as an alternative source of organs.¹⁷

Successful transplant of organs has been reported from poisoned donors associated with a variety of xenobiotics.¹⁸ Alternatively, organs from donors with xenobiotic poisoning, which is considered toxic to organ function by impairing enzymes, can be successfully transplanted if the cellular structure is otherwise maintained. Although some xenobiotics are highly toxic, such as cyanide and carbon monoxide, transfer of the clinical poisoning in the donor to the organ recipient has not been reported. This is likely caused by several factors, including xenobiotic metabolism, tissue redistribution, or binding prior to procurement, as well as the means of handling organs during the transplant process. Organ procurement from poisoned donors often reaches success rates similar to nonpoisoned donors when carefully selected.¹⁸ In a few studies, survival results after organ transplant in donors with drug poisoning versus donors without drug poisoning have been compared.^19-24

Iran is a leading country in organ transplantation and organ donation in cases of brain death, with the number of donations after brain death in Iran higher than in other countries in the region.^17,25 Unfortunately, studies in this area have been limited. Here, we evaluated organ transplant outcomes of brain dead donors following poisoning in Iran.

Materials and Methods

This study was first approved by the ethics committee of Shahid Beheshti University of Medical Sciences (code of ethics: IR.SBMU.RETECH.REC.1399.513). After permission from family was obtained, information was gathered on donors with brain death due to poisoning from 2006 to 2020 who were transferred for organ transplant from Loghman Hakim Hospital (poison center) to Masih Daneshvari, the Organ Procurement Unit of Shahid Beheshti University of Medical Sciences in Tehran, Iran. After confirmation with ancillary tests and a final confirmation of brain death, quality of organs for transplanting was evaluated.

Organ allocation for all candidate recipients was performed according to protocols established by the Iranian Ministry of Health authorities. With regard to liver transplant, after liver retrieval, a biopsy was performed to assess final suitability criteria. Results of biopsies were interpreted by an expert pathologist. Organ transplant recipients were evaluated for transplant success and recipient condition at 1 month and 12 months after transplant.

With regard to brain dead donors, studied parameters included age, sex, history of drug use and type of substance and disease, cause of poisoning, intoxication type, laboratory test results, electroen­cephalo­graph (EEG) results, cerebrovascular angio­graphy results, Doppler ultrasonography results, cause of hypoxia, length of hospital stay in the intensive care unit (ICU), cardiopulmonary resuscitation (CPR) and its frequency, information on vasopressor infusion, the organ transplanted, and outcomes of the transplant recipients. These parameters were collected from 2 centers.

Statistical analyses
We used SPSS software version 21 for statistical analysis. The population normality was assessed using the Kolmogorov-Smirnov test; t tests and one-way analysis of variance were then used for parametric data and chi-square for nonparametric data. P < 0.05 was considered as the level of significance.

Results

During our study period, 109 patients with brain death due to poisoning were transported to the transplant facility. Among these, 6 people died because of unstable hemodynamics prior to transplant, and 1 person who was a candidate for liver donation was excluded because of biopsy results.

Of the remaining 102 patients with brain death after poisoning who donated organs, poisoning was intentional in 51%, unintentional in 25.5%, and unknown in 23.5%. A medical history review of donors showed that 90.2% of donors were healthy, 3.9% had hypertension, 2% had ischemic heart disease, 1 person had anemia, 1 had history of seizure, and 1 had diabetes and hypertension (simultaneous). In terms of medication history, 79.4% of donors did not take any medication; among those who took medications, the most common were sedatives and hypnotics (2.9%), antipsychotics (2.9%), and tricyclic antidepressants (2.9%). Figure 1 shows the causes of toxicity in these patients; the most common reason for poisoning was the consumption of opioids (28.4%).

Table 1 shows donor demographics and results of laboratory tests. Six donors had been referred with prehospital sudden cardiac arrest; all 6 had been successfully resuscitated, and all their donated organs were in suitable condition. For recipients of these donors, grafts were successful 1 month and 12 months after transplant. In 25 donors, there was resistant metabolic acidosis. Acute kidney injury was seen in 30 donors, and emergency dialysis was performed in 23 donors to remove the toxin or to treat acute kidney injury.

Duration of hospitalization in the ICU for donors was as follows: 78.4% stayed less than 10 days, 18.6% stayed between 10 and 20 days, and 2.9% stayed more than 20 days. For 49% of donors, CPR was not performed. For donors who did receive CPR, 71.15% received CPR only once, 26.92% received CPR twice, and 1.93% received CPR 3 times. We observed that 92.2% of donors received vasopressor as treatment. With regard to EEG results, 76.5% showed flat and 23.5% showed severe diffuse brain injury. Color Doppler brain ultrasonography and brain angiography were performed for 23.5% and 3.9% of donors, respectively. Causes of hypoxia in donors were as follows: respiratory failure in 26.5%; CPR in 23.5%; seizure in 18.6%; CPR and seizure in 13.7%; respiratory failure, CPR, and seizure in 7.8%; respiratory failure and seizure in 4.9%; and respiratory failure and CPR in 4.9%.

With regard to organs donated, 85.3% of donors donated 2 or more organs. The most common donated organ was the liver (81.4%). Figure 2 shows the number of donated organs. In total, 271 transplant operations were performed on 269 organ recipients during the 14-year study period. Table 2 shows recipient results at 1 month and 12 months after organ transplant. After 12 months, 18 recipients had died of cardiac arrest, 1 died from pulmonary embolism, 1 from pneumonia, 1 from renal vein thrombosis, 1 from sepsis, and 1 from posttransplant bleeding.

Mortality in recipients whose donors stayed in the ICU for more than 10 days was significantly lower (P < .01) versus recipients whose donors stayed in the ICU for less than 10 days. We observed no significant difference in mortality between recipients whose donors had resistant metabolic acidosis or received CPR and other recipients of donors without these factors. Furthermore, no significant differences were observed in recipient mortality and graft rejection due to donor's age, sex, smoking, acute kidney injury, and opioid poisoning.

Discussion

Toxins cause brain death as a result of vulnerabilities of the central nervous system. With supportive care, these patients are suitable candidates for organ donation. Although some xenobiotics are highly toxic, such as cyanide and carbon monoxide, transferring clinical poisoning to the organ recipient has not been reported. This is likely caused by several factors, including xenobiotic metabolism, tissue redistribution, or binding prior to procurement, as well as how the organ was handled during the transplant process.¹⁸

No significant differences have been shown with regard to survival or transplant failure between poisoned donors and donors from other causes. Some studies have even shown that organ donation from poisoned donors has a lower rate of transplant rejection.^19-22,26-31 In a 2001 study that investigated outcomes of transplanted organs from donors after carbon monoxide poisoning (6 heart and 1 lung transplant), the success rate of heart transplant was 83.33%; however, the lung transplant recipient died 8 months after surgery due to Pneumocystis carinii pneumonia.²⁷ In our present study, there was 1 donor with carbon monoxide poisoning. Three organs were transplanted, and grafts in all recipients were successful (without death or graft rejection).

In another investigation of organ transplants from brain dead donors in the United States, transplants from brain death due to poisoning were reported to have significantly increased from 59 in 2000 to 1029 in 2016.²⁸ In a study from Whited and colleagues²⁴ that investigated lung transplants from donors with drug poisoning, the results showed that, between 2005 and 2014, the use of organs from drug poisoned donors increased from 1.86% to 6.23%. The investigators reported no significant differences in recipient survival rates at 1, 3, and 5 years after transplant between the 2 groups with different donors (drug and nondrug poisoning).²⁴

In a 2014 study of 6 kidney transplants from 3 donors with methanol poisoning, organ transplants were successful in all recipients.30 Although 2 of the recipients had postoperative complications, none of these were related to transplant or organ damage due to methanol poisoning.³⁰ In a study on liver transplants in Iran, of 1485 organ donors, there were 115 donors with poison death; among these, 74 successful liver transplants were performed. Although the incidence of reversed cardiac arrest and acute kidney injury in poisoned donors was 53.1% and 14.9%, respectively, and also 16.2% of poisoned donors required emergency dialysis, there was no significant differences in the 1-year and 5-year survival rates between the 2 target groups of poisoned and nonpoisoned donors.²³

In a 2020 study of organ donation after drug-related and non-drug-related brain deaths and donations after circulatory deaths, there were 81 donors for each group, with 264 organs transplanted from donors with drug-related deaths, 234 organs transplanted from donors with non-drug-related brain deaths, and 181 organs transplanted from donors after circulatory death. Short-term graft failure was 1.15% in the drug-related death group, 2.14% in the non-drug-related brain death group, and 5.52% in the circulatory death group. These results showed that organ transplant outcomes from donors with drug-related deaths were associated with less failure.²¹ The study results also showed that organs donated from poisoned individuals were associated with a very high survival rate in recipients and that graft rejection rate was low. This suggests that poisoning in donors is not transmitted to the recipient and that organs from poisoned donors should be considered like other donors.

In a 2018 study from Wood and colleagues on pesticide poisoned donors, organs donated after pesticide poisoning showed good graft function after transplant (survival rate was 96.7% in kidney transplant recipients, 71% in liver transplant recipients, 83% in cornea transplant recipients, and 67% in heart transplant recipients).²⁹ In our study, 3 donors were poisoned with pesticides (fumigant, organophosphate, and organophosphate and beta blocker). Nine organs were transplanted from these donors, and we did not observe any deaths or graft rejections in the recipients.

Among the toxins, methanol is highly toxic to the human body. Methanol is excreted unchanged by the lungs and kidneys. The remaining amount is metabolized in the liver. Complications of methanol poisoning include kidney failure, liver damage, heart and circulatory problems, and vision damage. On the other hand, treatment for methanol poisoning is ethanol, which is metabolized by the liver and excreted by the kidneys.^18,32 Several studies have reported that organ donation from a person poisoned with methanol is successful and that poisoning had no significant effect on organ function, especially lung, liver, and kidney. Recipient outcomes and even graft and recipient survival with these donors did not differ in the short and long term from transplants performed with organs from donors who died from other causes.^30,33-35 In our present study, the success rate of transplants from methanol-poisoned donors was 94.12%, which is a very satisfactory rate. There were also no graft rejections of donated kidneys, and only 1 of the transplanted livers failed.

A few studies have shown that performing CPR on donors does not significantly negatively affect donor organs and recipient outcomes.^36,37 In this study, 141 organs from CPR donors had been transplanted with a graft rejection rate of 0.71%, indicating that donor CPR did not have a negative effect on graft success.

Some studies have reported that survival rates are lower in recipients whose donors had acidosis,³⁸ whereas others have found no difference.^33,39 We found no significant differences between recipient mortality rates with resistant metabolic acidosis in donors and other donors. This indicates that resistant metabolic acidosis has no adverse effect on recipient survival.

The prolonged ICU stay in donors has been described as a risk factor for recipient survival rate,^39,40 but some authors have not reported any effect.^41,42 In our study, we found a positive effect of prolonged ICU stay (>10 days) on recipient survival rate.

Conclusions

Organ donation after poisoning-related brain death can be a good source of organs for people in need. In our study and others, patient survival after transplant from these donors is high and transplant rejection rate is low. If the candidate donor and organs are in optimal condition before the transplant, we suggest that there should be no exclusion for use of the graft.

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