Uncontrolled Donation Potential After Circulatory Death in Slovenia Could Lead to More Organ Donations: Extrapolation of SiOHCA Study Data

Abstract

Out-of-hospital cardiac arrest is one of the major health challenges faced by developed countries. Donation after circulatory death is a process of retrieving organs from individuals whose death has been confirmed by circulatory or respiratory criteria. In 2018, 136 625 people were listed on the waitlist covering over 16 countries. Out of these 136 625 individuals, 7383 died whilst waiting that year. The aim of this study is to assess the potential for the uncontrolled donation after circulatory death among out-of-hospital cardiac arrest patients in Slovenia. This non-interventional study was conducted using the Slovenian out-of-hospital cardiac arrest registry dataset. The database measured Out-of-hospital cardiac arrest in Slovenia between September and November 2022. From the database we chose patients who would be identified as donors by the uncontrolled donation after circulatory death guidelines for patient selection. Using the selection criteria we have narrowed the used data set from 294 unique patient records to 19. There were no organ donors in the cohort. With extrapolation we calculated that in 2022 there could be 111 donors in Slovenia that would fit the uncontrolled donation after circulatory death criteria. This equates to 52.4 pmp/y. We conclude that uncontrolled donation after circulatory death program in Slovenia would positively impact patients. Although our study is limited by a small sample of out-of-hospital cardiac arrest patients and short duration of the Slovenian out-of-hospital cardiac arrest registry inclusion, the results offer a good foundation to further explore uncontrolled organ donation in Slovenia and similar countries.

• What do we already know about this topic

• Uncontrolled Donation After Circulatory Death (uDCD) offers a valuable avenue for expanding the pool of organs available for transplantation. This approach is subject to stringent criteria that potential donors must meet. Currently, only a handful of countries have implemented uDCD programs, reflecting its specialized nature in the field of organ donation.

• How does your research contribute to the field?

• Prior to implementing an Uncontrolled Donation After Circulatory Death (uDCD) program, a health system must first evaluate the potential for such an initiative within the country. Our research extrapolates data from the SiOHCA registry to assess this potential specifically for Slovenia.

• What are your research’s implications toward theory, practice, or policy?

• Our research represents an initial step toward changing practices and policies to enable Uncontrolled Donation After Circulatory Death (uDCD) in Slovenia.

Introduction

Out-of-hospital cardiac arrest (OHCA) is one of the major health challenges faced by developed countries with approximately 275 000 in Europe. ¹ A study conducted using data from 12 national OHCA registries, encompassing 86 759 cases, revealed that the overall survival to hospital discharge was 10% (ranging from 6% to 22%). ²

There is a significant need for viable organs worldwide. In 2018, 136 625 people were listed on the waitlist in the USA, Eurotransplant, Scandiatransplant and the United Kingdom—covering over 16 countries. Out of these 136 625 individuals, 7383 died whilst waiting that year. ³

Organ donation after OHCA remains a rare method worldwide. In a study that included 3061 patients from the Paris area, organ explantation was performed in only 4.4% of patients who died in the intensive care unit after OHCA. ⁴ In Slovenia, an estimated 120 organ transplants are conducted each year, and there are approximately 200 patients registered on the waiting list. In 2022, the rate of utilized DBD (deceased after brain death) donors was 23.3 per million population per year (pmp/y) in Slovenia. Regrettably, 9 individuals in Slovenia lost their lives while awaiting organ transplantation during that year. ⁵

Donation after circulatory death (DCD) is a process of retrieving organs from individuals whose death has been confirmed by circulatory or respiratory criteria. ⁶ If death ensues following the withdrawal of life-sustaining therapies, when they are deemed not in the best interest of the patient, organ donation from such cases is classified as controlled DCD (cDCD). ⁶ In situations where a patient succumbs to an unforeseen cardiac arrest, with unsuccessful resuscitation efforts in the field and later at the hospital, the organ donation is referred to as uncontrolled DCD (uDCD). ⁶

According to the modified Maastricht classification of DCD donors, as revised in Paris in 2013, DCD donors can be categorized into distinct groups, as outlined in Table 1. ⁷

Table 1.

Maastricht Classification of DCD Donors as Revised in Paris in 2013. ⁷ .

Category and type of DCD
1: Cardiocirculatory death outside hospital (uncontrolled)
	1a: with no witness
	1b: with witnesses and rapid resuscitation attempt
2: Witnessed unexpected cardiocirculatory death with rapid resuscitation attempt (uncontrolled)
	2a: in ICU
	2b: in hospital (ER or ward)
3: Expected cardiocirculatory death with withdrawal of life-sustaining therapy (controlled)
	3a: in ICU
	3b: in OR with withdrawal phase > 30 min
	3c: in OR with withdrawal phase ≤ 30 min
4. Cardiocirculatory arrest in a brain-dead donor
	4a: unexpected (uncontrolled)
	4b: expected (controlled)
5. Medically assisted cardiocirculatory death (controlled)
	5a: in ward
	5b: in OR

Note. DCD = donation after cardiocirculatory death; ICU = intensive care unit; ER = emergency department; OR = operating room.

The inclusion and exclusion criteria for uDCD donors exhibit variation among countries. In 2022, the European Committee on Organ Transplantation presented Standard selection criteria for uDCD donors. The criteria specify that included patients should undergo advanced cardiopulmonary resuscitation within 15 to 30 min of a witnessed loss of consciousness or cardiac arrest. ⁸ Additionally, these patients are required to be between 18 and 60 years old, possess a known or suspected cause of death, lack exsanguinating lesions from chest or abdominal wounds, exhibit a normal external appearance (eg, without signs of parenteral drug addiction), and the time interval between cardiac arrest and the initiation of in situ preservation should be less than 150 min. ⁹

Due to the insufficient availability of organs from DBD patients, many European countries are progressively turning to organs from DCD donors. ⁶ The study conducted in Singapore revealed that the potential number of uDCD donors arising from all OHCA cases varied depending on the inclusion criteria employed. The estimated range was from 14.3 to 65.4 uDCD donors pmp/y. ¹⁰

The aim of this study is to assess the potential for uDCD among patients dying due to OHCA in Slovenia, laying the groundwork for possible implementation of uDCD both in Slovenia or other countries with comparable health system and population characteristics. We hypothesize that there are significant capacities to shorten the abdominal organ waiting lists in Slovenia.

Materials and Methods

Study Description and Formal Analysis

This retrospective non-interventional study was conducted using the Slovenian out-of-hospital cardiac arrest registry (SiOHCA) dataset. ¹¹ The SiOHCA database measured OHCA in Slovenia between September and December 2022, recruiting patients between September and November 2022 (3 months). The follow-up period was 30 days. There were 2 points for data intake, one on the day of OHCA and one at 30 days after OHCA. Data was collected digitally through SiOHCA website and was inputed by the EMS doctor for each included EMS station, that collected paper forms from all the OHCA cases that were attended to by the EMS station. This study was approved by The National Medical Ethics Committee of the Republic of Slovenia (application number 0120-153/2022/3). No written consent from the patients was sought after, as the nature of the OHCA pathology means that patients are unable to sign the consent. The study did not change the clinical care of the patient.

Case Selection

From the database created by SiOHCA we chose those patients who would be identified as donors by the uDCD guidelines and fit the definition of 1a and 2a/b (Table 1). ⁸ The database was thus filtered to select those patients who fit the inclusion criteria bellow, except other illnesses which SiOHCA did not track in the resolution necessary to filter the cases out (see Supplement 1, Table 1). The cases not fitting the criteria were discarded. The study size was not planned in advanced. The EMS services volunteered to be a part of SiOHCA. Case selection is shown in figure below (Figure 1).

Figure 1.

Patient selection.

Measurements

From the original SiOHCA database, encompassing 159 variables we selected 28 data variables identified as important for uDCD. The selected variables are part of Utstein 2015 reporting template (see Supplement 1, Table 2. ¹² Due to the closed-ended questions there was no bias in reporting, no other biases were addressed.

Table 2.

Sample Characteristics.

Gender and age	Measured data	Missing data
Men (n, % of sample)	19 (100)	0 (0)
Age (mean years, CI90)	53.32 (59.2)	0 (0)
Cause of CA		0 (0)
Medical (n, % of sample)	15 (79)
Trauma (n, % of sample)	1 (5)
Unknown (n, % of sample)	3 (16)

Extrapolating Outcomes to the Whole Slovenian Population

The study catchement population was 1 274 398 persons reported by EMS services collecting data. The population of Slovenia at the end of 2022 was 2 110 547 and there were 1 169 019 persons between the age 18 and 60 years old. Of those 18 to 60 years old, 803 749 persons from SiOHCA database were inside our catchement area. The coefficient that we used to extrapolate our results to the entire Slovenian population and whole calendar year (12 months) is shown in equation (1). All of the measured counts were multiplied by k (equation (1)).

$$k=t*p=4*\frac{1,169,019}{803,749}=4*1.454=5.816$$ (1)

Equation (1): Extrapolating the study results to the whole population for 1 year (k: multiplication factor to extrapolate number of cases to the whole study for 1 year, t: time correction for 1 quarter of a year—3 months, p: population correction).

Deceased donors per million population per year were calculated using equation bellow (equation (2)).

$$pmp/y=\frac{uDCD*k}{p_m}$$ (2)

Equation (2): Calculation of deceased donors per million population per year (pmp/y: Deceased donors per million population per year, uDCD: number of cases fitting the selection criteria inside our sample, k: multiplication factor to extrapolate number of cases to the general population inside a single year, p_m: million population).

The analysis was performed using Python version 3.9.6 (RRID:SCR_008394), Pandas (RRID:SCR_018214), Matplot libraries (RRID:SCR_008624) and the Jupyter Notebook (RRID:SCR_018315). The data bellow is generated using frequencies, mean and confidence interval of the 90th percentile. There were no subgroups analyzed and compared between. Missing data was not counted. The manuscript methodology is described according to The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement (RRID: SCR_018788). ¹³

Slovenian Legislation

In Slovenia, individuals aged 15 and above have the formal prerogative to express their desire to become organ donors posthumously. In such instances, the transplant coordination team conducts an informative discourse with the donor’s relatives, proceeding with the organs and tissues donation process if the donor meets the established inclusion criteria. Conversely, individuals also possess the right to communicate their decision not to become organ donors. In cases where there is no pre-existing record of the potential donor’s preferences, a transplant coordinator apprises the deceased’s relatives about the prospect of organ retrieval. The decision to permit the donation then rests with the deceased’s relatives. ¹⁴

Results

Using the selection criteria we have narrowed the used data set from 294 unique patient records to 19 (Figure 1). Main characteristics of the sample are shown in Table 2.

Times in the Clinical Path of the Patient

The average EMS response time (from call to arrival) was 782.68 (CI90: 1231.6) s, the average time to their departure was 3156.11 (CI90: 4276.4) s. Other times from the emergency call being answered to various event important to the chain of survival are shown in Table 3.

Table 3.

Times From Call Pick-up to Events in Chain of Survival.

Event	Seconds from call pickup to event
TCPR instructions given (mean seconds, CI90)	130 (277.6)
Bystander CPR start (mean seconds, CI90)	269.33 (492.0)
EMS on scene (mean seconds, CI90)	782.68 (1231.6)
EMS CPR start (mean seconds, CI90)	982.32 (1546.4)
First EMS defibrillation (mean seconds, CI90)	1128.00 (1950.5)
Drugs application (mean seconds, CI90)	1334.32 (2004.0)
ROSC (mean seconds, CI90)	2020.50 (2498.5)
Left scene (mean seconds, CI90)	3156.11 (4276.4)

Note. TCPR = telephone cardiopulmonary resuscitation instructions; CPR = cardiopulmonary resuscitation; EMS = emergency medical services; ROSC = return of spontaneous circulation; CI90 = confidence interval 90th percentile, 15. min = 900 s

Other case characteristic are described in Table 4.

Table 4.

Other Case Characteristics.

Characteristics	Number of cases (N = 19)
Witnesses
Eyewitness/bystander	17
EMS	2
CPR performed by
Eyewitness/bystander	11
EMS	7
First responder	1
CPR technique
Only chest compressions	8
No CPR	7
Mouth-to-mouth ventilation with chest compressions	2
Dispatch service
Recognized cardiac arrest	12
Missed cardiac arrest	3
TCPR
TCPR instructions given	19
TCPR instructions not given	0
First responders
Sent to the scene	6
Was not sent to the scene	7
Organ donations
Donors	0
ECMO
ECMO used	0

Note. EMS = emergency medical services; CPR = cardiopulmonary resuscitation; TCPR = telephone cardiopulmonary resuscitation; ECMO = extracorporeal membrane oxygenation.

Extrapolation to Slovenian Population

Using above described methodology we can extrapolate that there could be 111 donors in Slovenia that would fit the uDCD criteria in 2022. This equates to 52.4 pmp/y (Figure 2). Based on our sample we could expect roughly 222 more kidneys and 111 livers for transplantation with implementation of uDCD in perfect conditions.

Figure 2.

Chart showing comparison of Actual deceased donors in Slovenia in 2022 ⁵ (in blue) and the calculated potential combining the Actual deceased donors and Uncontrolled donation after circulatory death (in violet).

Note. pmp/y = per million population per year.

Discussion

This study is the first known review of uDCD potential in Slovenia. This retrospective analysis involved extrapolating data from the SiOHCA data set to estimate the possible annual number of donors in the entire Slovenian population aged 18 to 60 years old in ideal circumstances. In 2022, Slovenia recorded a rate of 26.54 actual deceased donors (DD) per million population per year (pmp/y). Spain, by contrast, recorded 46.03 actual DD pmp/y. ⁵ Our projected potential of eligible uDCD donors in Slovenia for the year 2022 is 52.4 pmp/y. Although the potential is noteworthy, the number of individuals who might end up being actual donors is uncertain.

The DCD transplantation programs are growing all over the world. As of 2019, several European and other countries have already implemented uDCD programs. Certain countries permit both cDCD and uDCD, whereas others have chosen to restrict the program to only one of them, usually cDCD. ¹⁵

Spanish study demonstrated that the utilization of the uDCD program successfully shortened their kidney transplantation waiting lists and resulted in a notable rise in the annual rate of DCD transplants, which was 1.75 times higher in 2015 compared to 1996. ¹⁶ It was estimated that the use of uDCD donors might had lead to a 25% rise in donation rates in Spain and France. ¹⁷

Potential for uDCD Transplantations in Slovenia

As far as we know, this is the first attempt to quantify the medically suitable uDCD donors among patients in Slovenia. In Slovenia, individuals have the option to posthumously donate their heart, kidney, liver, pancreas and lungs as part of the Donation After Brain Death program (DBD). As of the time of writing this paper, there is no established DCD program in Slovenia. After circulatory death, the deceased can donate certain tissues. Consequently, the tissue most frequently eligible for donation after DCD in Slovenia is cornea.

uDCD programs around the world have the potential to significantly increase the number of organs available for donation. ¹⁵ The 2015 European Resuscitation Council Guidelines recommend assessing for potential uDCD following unsuccessful resuscitation attempts. In such cases, continuing circulatory support, like ECMO, should be considered. ¹⁸

Our study projects that, with the inclusion criteria described in the Methods, Slovenia could have 111 eligible donors for uDCD following OHCA annually. Considering there were 49 utilized donors in Slovenia in 2022 and that on the last day of 2022 there were 82 persons waiting for a kidney transplant and 16 for liver transplant, we could theoretically give organs to all of those patients (we actually need at least a match in blood type and organ size). That could reduce the waiting time for organ recipients. ⁵ In 2022, a total of 2991 kidneys and 1483 livers were transplanted across the entire Eurotransplant region. ¹⁹ Based on our statistics, Slovenia has the potential to provide additional 222 kidneys and 111 whole livers annually, provided that the potential pool of eligible uDCD donors is fully utilized. Not all donors who meet the criteria are used for organ donation. Moreover, not all donated organs are ultimately utilized. ¹⁵

The European recommendations suggest that the duration of time without blood flow should not exceed 15 to 30 min. ⁸ Our study found that the duration from answering a call to the start of CPR by EMS was 16.37 min (982.32 s), suggesting that Slovene EMS system is effective enough for the adoption of uDCD, and that most of the patients would be below the 30 min threshold.

First responders were the first ones who performed CPR in just 1 case in our study. Nevertheless, it is crucial to acknowledge the significance of first responders, since they have the ability to reach the location before EMS teams, when both are alerted simultaneously. According to a report from Maribor, first responders came before EMS teams in 96.67% of cases where both were activated. First responders arrived, on average, 10.13 min earlier. ²⁰ These times could be even further decreased if more bystanders did CPR, as in 37% of cases in our cohort, the CPR was not done by bystanders witnessing the arrest.

The European recommendations specify that the total warm ischemia time should not exceed 150 min in order for a patient to be considered as a donor for the uDCD. ⁸ The average time for EMS crews to depart from the location of a cardiac arrest in our study was 52.6 min (3156.11 s), as shown in Table 3. Due to the geographical peculiarities of Slovenia and the organization of the EMS system, it may not always be feasible for EMS teams to reach the hospital within the vital 150-min timeframe outlined in European recommendations. ⁸

The predictability of donor utilization is hindered by various factors, including instances where doctors fail to identify or refer eligible donors, unconfirmed diagnoses of brain death, failure to confirm circulatory death within the required timeframe, logistical challenges, and a shortage of suitable recipients. ²¹

Comparison With Other Countries

uDCD programs have been established in Europe for several decades. Since the 1980s, numerous countries have successfully implemented uDCD programs, leading to notable outcomes. Between 2000 and 2014, Spain recorded 1247 uDCD donors, France reported 414 donors, and The Netherlands registered 159 donors. ²²

A study conducted in the United States estimated that the potential pool of uDCD donors from 2013 to 2016 comprised 9828 individuals. ²² In Singapore, research concluded that their potential for uDCD ranged from 14.3 to 65.4 donors pmp/y. ¹⁰ Our findings, which indicate 52.4 uDCD donors pmp/y, are consistent with this range.

Evidence from the Netherlands indicates that calculating potential should not rely solely on resuscitation databases without considering geographical factors. Their findings highlight that uDCD programs are significantly more effective in urban areas. ²³

The article presents an incentive for other countries in the region with similar structure of EMS organization to explore their uDCD potential as well. For instance, Bosnia and Herzegovina, which has an OHCA incidence of 62 per 100 000 inhabitants per year, might possess untapped uDCD potential, despite challenges such as bystander involvement rate and limited accessibility to AEDs.^24,25 Similarly, the Republic of Croatia may also possess unexplored potential, with approximately 8000 individuals experiencing OHCA annually. ²⁶

Limitations

In the present study we only extrapolate the data generated by SiOHCA in 2022, only recruiting patients for a part of the whole country and only for 3 months. The aim of that data collection was epidemiology of OHCA in Slovenia and not calculation of uDCD potential, thus the data that would give the full picture was not entirely collected. Chronic and active diseases were not covered, but were rather just marked as present and thus disregarded from our analysis. The potential described in our study may be overestimated due to that.

The variation in inclusion criteria employed by different countries to choose eligible donors has the potential to impact our projections. ²⁷

The extrapolation was conducted utilizing official statistical data from 2022 in conjunction with our proprietary coverage calculations. We ascertained that our study encompassed a population of 1 274 398 individuals. This figure was derived from the population data of municipalities that EMS services indicated they cover. Due to the unavailability of official data, we were compelled to rely on the coverage reported by the EMS services.

Our study encompassed a substantial demographic segment. Nevertheless, potential disparities in non-participating regions could introduce variability into the study outcomes. Moreover, our methodology depended on EMS personnel for the comprehensive reporting of all OHCA incidents within their designated service areas. The potential omission of certain cases from the reported dataset may have resulted in an underestimation of the potential of uDCD.

The sample size had an impact on the statistical analysis that authors could not correct for due to inherently small sample size. Adhering to the established patient selection protocols, we refined our sample to 19 individuals. The study’s findings suggest that a uDCD program result in 52.4 pmp/y donations in Slovenia. However, the small sample size may have influenced this estimation, leading to uncertainty regarding the potential magnitude of error in the estimation. We utilized our proprietary formula to project outcomes for the entire Slovenian population. Such calculations have not been previously documented in literature, and there are no universally recognized formulas obtainable for authors to follow.

Conclusions

We conclude that implementing an uDCD program in Slovenia could significantly reduce organ waitlists. The potential for organ donation in cases of OHCA is substantial and should be considered in legislation to enhance the number of organ explantations. Educating lay bystanders to initiate CPR promptly could further increase the availability of suitable uDCD organs by reducing the time between cardiac arrest and the start of CPR. Although our study is limited by a small sample size of OHCA patients and the brief duration of SiOHCA recruitment, the findings provide a foundation for further exploration of uncontrolled organ donation in Slovenia and similar countries.