The Effect of Donor Transportation on the Function of Donor’s Organs

doi:10.21203/rs.3.rs-952422/v1

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The Effect of Donor Transportation on the Function of Donor’s Organs

https://doi.org/10.21203/rs.3.rs-952422/v1

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Background: The impact of donor transportation on the outcome of deceased organ donation remains largely unknown. This study aimed to investigate the effect of donor transportation on the function of the donor’s organs.

Methods: From 2016 to 2018, 139 donors of successful deceased organ donation from the local (primary) hospitals transferred to our hospital were included for analysis. Blood samples were drawn immediately after the donor admitted to our hospital (pre-transport data) and before donation (post-transport data) to assess the donor’s organ functions by determining the levels of blood biochemical indexes.

Results: The donor with a transport distance >200 km had higher post-transportation AST and a bigger change of TB level as compared with those with a transport distance < 200 km. Pearson’s correlation analysis showed a positive correlation between transport distance and post-transport AST. The donors with cardiac arrest history had significantly higher pre-transport AST, pre-transport ALT, post-transport ALT, post-transport BUN, and the change level of BUN after transport as compared with those without cardiac arrest history. The donors with a history of cranial decompression surgery had significantly lower pre-transport AST, pre-transport ALT, and post-transport Cr as compared with those without a history of cranial decompression surgery.

Conclusion: These results suggested that long-distance donor transportation may result in organ function deterioration, especially for donors with a cardiac arrest history. Donors with a history of intracranial decompression surgery can alleviate this problem.

Medical Genetics

donor transportation

deceased organ donation

donor organs function

Organ transplantation is a highly effective treatment for the end-stage failure of most essential organs, but organ shortage remains the greatest limiting factor to organ transplantation [1]. Various approaches have been adopted to address the problem of organ shortage, such as living organ donation [2], paired donor exchange [3], donation after circulatory death [4], and expanded criteria donors[5]. However, little attention has been paid to the donated organ damage and wastage caused by the donation process.

The majority of donors of deceased organ donation in our hospital are from the local (primary) hospitals. The donors or/and their families have organ donation wishes in local hospitals and the donors are transferred to our hospital for organ procurement. In clinical practice, however, a small proportion of donors died during or after transportation and ultimately failed to complete the organ donation. This loss undoubtedly aggravates the problem of "organ shortage". On the other hand, of the successful donation cases, there are some cases of emergency donations that fail to complete the pre-donation assessment and may pose a health risk to organ recipients.

Although previous studies have reported the relationship between long-distance transportation of grafted organ and graft outcome[6–11], nevertheless, the impact of donor transportation on the outcome of deceased organ donation remains largely unknown. Therefore, the purpose of this study was to investigate the effect of donor transportation on the function of the donor’s organs.

Study subjects

This was a retrospective study. The inclusion criteria were: 1) the donors of deceased organ donation from the local (primary) hospitals transferred to our hospital for organ procurement; 2) all deceased organ donation cases were supervised by the organ procurement organization and the Guangdong Provincial Red Cross Society. The exclusion criteria included: 1) donation was terminated due to the willingness of the family after the start of the donation process; (2) the donation cases had no transfer process. From 2016 to 2018, 139 donors of successful deceased organ donation were included for analysis. The distance between the local hospitals to the authors’ hospital mainly ranges from 150-350 km. This study was approved by the institutional review board (IRB) of our hospital and written informed consent was waived by the IRB due to the retrospective nature of this study. The Declarations of Helsinki and Declaration of Istanbul guidelines are followed and that no executed prisoner was used as a donor.

Data collection

Donor’s organ functions were assessed by blood biochemical indexes. Blood samples drawn immediately after transfer to our hospital were used for determining the pre-transport data, while the last blood draw before donation (approximately 24-48 hours after completion of transfer) was for the post-transport data. The blood biochemical indexes included aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), sodium (Na), blood urea nitrogen (BUN), creatinine (Cr).

Statistical analysis

Continuous data were indicated with mean ± standard deviation (SD). For the comparisons between two groups, the student’s independent t-test or Mann-Whitney U test (if normality was not assumed) was used. Categorical data were indicated with number and percentage (%), and the distribution would be tested with the Chi-square test or Fisher’s exact test (if any expected value <= 5 was observed). Pearson’s correlation coefficient was used to investigate the relation between two continuous variables. A P<0.05 would be recognized as reaching the significance of each test, two-tailed. All analyses were performed using IBM SPSS Version 25 (SPSS Statistics V25, IBM Corporation, Somers, New York).

Donors’ demographic and clinical characteristics

Donors’ demographic and clinical characteristics were summarized in Table 1. A total of 139 donors (mean age= 42.93±14.94 years, male/female=120/19) were included in this study. Of them, 133 (95.68%) cases had finished donation while 6 (4.32%) cases did not due to multiple reasons. Among 133 successful donations, 107 (80.45%) cases were donation after cardiac death (DCD) while 26 (19.55%) cases were donation after brain death (DBD). The major causes were cerebrovascular accident (59.71%), followed by traumatic brain injury (30.94%). The mean transport distance before transplantation was 177.64±99.66 kilometers (range: 5 to 375.9 km). There were 12 (8.63%) cases undergoing emergency procurement, 23 (16.67%) cases with a history of cardiac arrest, and 61 (44.20%) cases receiving cranial decompression surgery before donation.

Subgroup analysis stratified by transportation distance

To investigate if transportation distance had an impact on the laboratory indexes, donors were dichotomized into the >200 km group and <200 km group according to their transportation distance. The results showed that the >200 km group had higher post-transport AST (67.00±45.19 vs. 143.42±212.50, P=0.021, Table 2) and bigger change of TB level (0.73±14.72 vs. 6.34±13.35, P=0.048, Table 2). The distribution was also demonstrated in scatter plots for ATS (Figure 1) and TB (Figure 2). Pearson’s correlation analysis showed a positive correlation between transport distance and donors post-transport AST (Pearson’s correlation coefficient r=0.2, P=0.045).

Subgroup analysis stratified by cardiac arrest history

Subgroup analysis of clinical characteristics was conducted to compare between donors with and without cardiac arrest history. As shown in Table 3, the donors with cardiac arrest history had significantly higher pre-transport AST (105.98±166.10 vs. 244.33±446.15, P=0.032), pre-transport ALT (75.64±135.77 vs. 158.73±267.39, P=0.035), post-transport ALT (81.28±190.73 vs. 100.93±122.08, P=0.036), post-transport BUN (14.78±9.31 vs. 20.65±8.98, P=0.010), and BUN (change) (3.39±6.68 vs. 7.41±6.97, P=0.035) as compared with those without cardiac arrest history.

Subgroup analysis stratified by history of cranial decompression surgery

Subgroup analysis of clinical characteristics was also conducted to compare between donors with and without a history of cranial decompression surgery. As demonstrated in Table 3, the donors with a history of cranial decompression surgery had significantly lower pre-transport AST (168.90±295.00 vs. 67.00±42.58, P=0.029), pre-transport ALT (117.10±205.35 vs. 47.07±46.84, P=0.033), and post-transport Cr (250.19±231.85 vs. 167.24±134.81, P=0.040) as compared with those without a history of cranial decompression surgery.

It is well known that cold ischemic time has an important effect on donor organ quality and graft survival in deceased organ donation [12,13]. Supporting this notion, Gámez Córdoba et al. have reported that graft transportation influences primary dysfunction and graft survival [6]. Huang et al. also demonstrated that airplane transport of grafted livers can reduce graft survival following liver transplantation [11]. However, the influence of donor transportation on the outcome of deceased organ donation remains to be elucidated.

In this study, we investigated the effect of donor transportation on the function of the donor’s organs. The results showed that the donor with a transport distance >200 km had higher post-transportation AST and a bigger change of TB level as compared with those with a transport distance < 200 km. Pearson’s correlation analysis showed a positive correlation between transport distance and post-transport AST. AST and ALT are enzymes found mainly in the liver, red blood cells, heart cells, muscle tissue, pancreas and kidneys, and can be released into the blood by the injured liver or muscle cells and are used as indicators for injury of these organs [14]. TB is a biomarker for liver disease [15]. Thereby, these results suggested that long-distance transportation may lead to unstable vital signs of the donors, which should be attributed to the bumps during transport.

Subgroup analysis showed that the donors with cardiac arrest history had significantly higher pre-transport AST, pre-transport ALT, post-transport ALT, post-transport BUN, and the change level of BUN after transport as compared with those without cardiac arrest history. BUN is a marker for kidney function [16]. Elevation of the BUN level suggests kidney disease and increased risk of cardiovascular events in patients with acute heart failure [17]. Therefore, this result suggested that donors with a history of cardiac arrest had a greater risk of organ damage after transportation as compared with those without a history of cardiac arrest, which may be attributed to the instability of vital signs caused by the bumps during transport.

Our subgroup analysis also revealed that the donors with a history of cranial decompression surgery had significantly lower pre-transport AST, pre-transport ALT, and post-transport Cr as compared with those without a history of cranial decompression surgery. Serum Cr is also a commonly used marker of kidney function [18]. Since most of the donors had a cerebrovascular accident or traumatic brain injury, intracranial pressure may be increased during transportation, causing unstable vital signs and increased organ damage. However, the craniocerebral decompression surgery may alleviate the increased intracranial damage caused by the bumps during transportation.

In clinical practice, some donors had unstable vital signs during transportation, and the transportation team had recommended that urgent organ procurement should be implemented. Therefore, as soon as the donor arrived, the transplant team quickly completed the preoperative preparation and performed organ procurement to avoid organ wastage. Therefore, organ damage caused by transportation is sometimes inevitable, and establishing a transportation team with professional critical illness assessment and the well communication among different departments can also avoid organ wastage caused by transportation.

Several limitations to this study should be pointed out. Theoretically, the pre-transport data should be based on the blood samples drawn in the local hospital immediately before the transport, however, it cannot be achieved. Therefore, the blood samples drawn immediately after transfer to our hospital were used for determining the pre-transport data. In addition, although we found some significant differences in the post-transport data in our intergroup comparison, however, there were no significant differences between the pre-transport and post-transport data. Including the non-transport donors as a control group allows a more comprehensive assessment of the impact of donor transportation. Moreover, this study did not analyze the postoperative recovery of the recipient, thereby it could not provide stronger evidence to support our findings. In the future, a well-designed study with a large sample size should be conducted to validate the findings of this study.

In summary, our results suggested that long-distance donor transportation may result in organ function deterioration, especially for donors with a cardiac arrest history. Patients with a history of intracranial decompression surgery can alleviate this problem. Donor transportation should be avoided and the grafted organs should be procured at the local hospital after complete assessment as much as possible.

ALT: alanine aminotransferase; AST: aspartate aminotransferase; BUN: blood urea nitrogen; Cr: creatinine; DBD: donation after brain death; DCD: cardiac death; SD: standard deviation; TB: total bilirubin

Ethics approval and consent to participate

This study was approved by the institutional review board (IRB) of the Third Affiliated Hospital of Sun Yat-sen University.

Written informed consent was waived by the institutional review board (IRB) of the Third Affiliated Hospital of Sun Yat-sen University due to the retrospective nature of this study.

Consent for publication

Not applicable.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Competing interests

The authors declare that they have no competing interests.

Funding

This work was supported by the Natural Science Foundation of Guangdong Province [No. 2018A0303130305].

Authors' contributions

We declare that all the listed authors have participated actively in the study and all meet the requirements of the authorship. Drs. Huimin Yi and Tianwei Xiong designed the study and wrote the protocol, Drs. Jianrong Liu, Zhuchun Wang, Yuling An, Xuxia Wei, Ziyu Li, and Mingming Fan acquired the manuscript, Drs. Jianrong Liu, Zhuchun Wang, Xiaomeng Yi, Qian Xu, Weijian Chen and Yue’e Tang analyzed the data, Drs. Jianrong Liu and Zhuchun Wang wrote the first draft of the manuscript and mainly revised the manuscript. All authors approved the final version of the manuscript.

Acknowledgements

None declared.

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Table 1. Donors’ demographic and clinical characteristics

Parameters	All (n=139)
Donation year
2016	36 (25.90%)
2017	50 (35.97%)
2018	53 (38.13%)
Age, year	42.93±14.94
Sex
Male	120 (86.33%)
Female	19 (13.67%)
Donation results
Done	133 (95.68%)
Gave up	6 (4.32%)
Donation type
DCD	107 (80.45%)
DBD	26 (19.55%)
Causes of death
Cerebrovascular accident	83 (59.71%)
Traumatic Brain Injury	43 (30.94%)
Cerebral hypoxia and ischemia	4 (2.88%)
Poisoning	1 (0.72%)
Brain tumor	1 (0.72%)
Cardiovascular accident	3 (2.16%)
Others	4 (2.88%)
Transport distance, km	177.64±99.66
Emergency procurement
No	127 (91.37%)
Yes	12 (8.63%)
Cardiac arrest history
No	115 (83.33%)
Yes	23 (16.67%)
Cranial decompression surgery
No	77 (55.80%)
Yes	61 (44.20%)

Table 2. Comparisons of laboratory index by distance group (per 200 km)

Parameters	<200 km	>200 km	P
Pre-transport
AST	86.20±106.68	157.65±291.56	0.125
ALT	67.61±140.74	103.70±177.88	0.272
TB	16.71±11.99	13.86±9.84	0.192
Na	153.16±12.30	157.54±15.33	0.125
BUN	12.30±9.91	11.19±7.84	0.530
Cr	197.67±173.09	172.26±151.70	0.435
Post-transport
AST	67.00±45.19	143.42±212.50	0.021
ALT	56.09±72.26	105.89±232.21	0.173
TB	17.44±15.93	20.20±18.49	0.432
Na	154.58±12.39	156.56±14.56	0.473
BUN	16.04±9.98	15.36±9.11	0.725
Cr	238.73±231.69	197.91±173.31	0.313
Change
AST	-19.20±96.04	-14.23±228.42	0.893
ALT	-11.52±80.11	2.19±212.60	0.686
TB	0.73±14.72	6.34±13.35	0.048
Na	1.43±9.88	-0.98±15.00	0.360
BUN	3.74±6.22	4.18±7.33	0.750
Cr	41.06±116.07	25.65±126.16	0.530

AST, aspartate aminotransferase; ALT, alanine aminotransferase; TB, total bilirubin; Na, sodium; BUN, blood urea nitrogen; Cr, creatinine.

Table 3. Cardiac arrest history and cranial decompression surgery

	Cardiac arrest history			Cranial decompression surgery
Parameters	No (n=111)	Yes (n=22)	P	No (n=74)	Yes (n=59)	P
Age, year	43.94±14.91	37.77±15.14	0.080	41.92±14.52	44.17±15.76	0.280
Transport distance, km	178.05±98.32	195.20±101.48	0.458	189.32±97.47	170.30±99.97	0.377
Pre-transport
AST	105.98±166.10	244.33±446.15	0.032	168.90±295.00	67.00±42.58	0.029
ALT	75.64±135.77	158.73±267.39	0.035	117.10±205.35	47.07±46.84	0.033
TB	14.29±9.73	19.74±15.52	0.073	16.45±10.36	13.20±11.39	0.012
Na	155.69±14.45	155.27±13.06	0.915	154.47±11.29	157.26±17.50	0.332
BUN	11.40±9.03	13.24±7.14	0.455	12.22±9.99	10.90±6.74	0.459
Cr	180.26±156.47	200.95±190.21	0.648	200.78±182.11	158.81±123.59	0.198
Post-transport
AST	101.31±163.16	160.67±180.05	0.203	132.98±205.01	78.02±78.05	0.102
ALT	81.28±190.73	100.93±122.08	0.036	104.78±229.51	55.29±68.17	0.179
TB	19.31±18.37	17.19±10.40	0.666	19.47±17.01	18.33±18.09	0.748
Na	155.54±13.58	156.59±14.36	0.785	155.91±13.09	155.40±14.51	0.852
BUN	14.78±9.31	20.65±8.98	0.010	16.76±10.41	14.10±7.77	0.163
Cr	205.16±182.93	276.07±283.23	0.209	250.19±231.85	167.24±134.81	0.040
Change
AST	-4.66±132.94	-83.67±352.26	0.122	-35.92±232.05	11.02±58.85	0.203
ALT	5.64±169.62	-57.80±149.93	0.178	-12.32±216.18	8.21±47.08	0.547
TB	5.02±14.18	-2.55±12.67	0.056	3.02±12.41	5.13±16.40	0.463
Na	-0.15±13.41	1.33±10.77	0.687	1.45±10.36	-1.86±15.96	0.209
BUN	3.39±6.68	7.41±6.97	0.035	4.54±7.72	3.20±5.36	0.332
Cr	24.91±112.08	75.11±164.00	0.141	49.40±143.66	8.43±76.25	0.095

AST, aspartate aminotransferase; ALT, alanine aminotransferase; TB, total bilirubin; Na, sodium; BUN, blood urea nitrogen; Cr, creatinine.

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The Effect of Donor Transportation on the Function of Donor’s Organs

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