Withdrawing treatment of Children in the pediatric intensive care unit of a China Children’s Hospital: A Single Center Years Retrospective Analysis

Background: Published data and practice recommendations on end-of-life generally reflect Western practice frameworks, there are few reports that refer to withdrawing treatment of children in China. Methods: Withdrawing treatment and reasons of children in the pediatric intensive care unit (PICU) of a regional children's hospital in eastern China from 2006 to 2017 was studied retrospectively. Withdrawing treatment was divided into medical withdrawing and premature withdrawing as defined. Results: The incidence of withdrawing treatment among children in the PICU decreased significantly, for premature withdrawing from a 3-year average of 15.1% in 2006–2008 to 1.9% in 2015–2017 (87.4% reduction). The decrease in cases of premature withdrawing contributed most of the decrease in total withdrawing. The median age of children in whom treatment was withdrawn increased from 14.5 (interquartile range: 4.0–72.0) months in 2006 to 40.5 (interquartile range: 8.0– 99.0) months in 2017. Reasons given by guardians of children whose treatments were withdrawn in 2011–2017, “illness is too severe” ranked first, accounting for 66.3%, followed by “condition has been improved” (20.9%). Only a few of the guardians ascribed withdrawing treatment to economic reasons. Conclusions: The decreasing in incidence of withdrawing treatment and an increase in the age of children whose treatment was withdrawn show that guardians are more willing to actively treat their children in this children’s hospital during the last years. Chinese children's guardians have their own unique ways of expression when self-reported reasons for withdrawing treatment.

Western practice frameworks [1,2]. In regions with different social cultures, religions, ethnicities, health care levels, and economic development, people often have different attitudes toward withdrawal of treatment. Even in the same region, there are controversial opinions regarding withdrawing treatment [1,3,4]. China has the largest number of children in the world, with 220 million children aged 0-14 years [5]. The Chinese government implemented the Children's Development Program of China (2011-2020) in 2011 with the aim to reduce the mortality of infants and U5MR to < 10‰ and 13‰, respectively [6]. Five years after implementation of the program, the interim statistical monitoring report showed that the infant mortality rate and the U5MR were reduced by 5‰ and 5.7‰ compared to 2010, respectively [7]. However, the report did not provide the statistical data pertaining to withdrawing treatment in critically ill children, which would have contributed to infant mortality and U5MR, and studies on treatment abandonment in pediatric intensive care units (PICUs) in China are lacking.
There is currently no relevant legislative provision in China for withdrawing treatment [8].
Due to the special relationship between physicians and patients and the lack of related laws, whether or not to withdraw treatment is often decided by the child's guardians, although these decisions may not be in the best interest of the child. Key decisions may include whether or not to use antibiotics in the instance of life-threatening infections and cardiopulmonary resuscitation in the event of cardiac arrest or to escalate to emergency or intensive care settings if the child becomes unstable [9]. In the past few decades, economic, healthcare, and social conditions in China have changed significantly. To better understand withdrawal of treatment in China, we report the associated data at a regional children's hospital in eastern China during the last years.  (2) children whose treatments were withdrawn. The exclusion criteria were as follows: (1) admission to the PICU, but subsequently transferred to the general wards or departments;

Methods
(2) > 14 years of age; (3) in a near-death state and treatment was abandoned at the time of admission; and (4) children with brain death.

Definition of withdrawing treatment
Withdrawing treatment was divided into two categories, defined as follows: (1) medical withdrawing: the child was in a permanent, irreversible coma or inevitable dying condition, treatment in a child for whom pursuing treatment was futile, and the guardian requested the medical staff to limit or withdraw life-sustaining treatment; (2) premature withdrawing: also was defined as treatment abandonment, guardian refusal for active treatment of a severely ill child for which treatment was indicated or for which there was some chance of survival, including the following situation, (a) the guardian took the child from the hospital and did not state the reason(s), (b) the child was still severely ill and the guardian did not authorize any medical treatments or partial treatments and requested for discharge for other reasons.
3 Data collection and reporting of reasons for withdrawing.
The age, gender, place of residence, type of disease, length of stay in the PICU, and condition at the time of discharge were collected from the hospital database (data for treatment were collected from the "informed consent" and "doctor-patient conversation record" documents. These documents also recorded the guardian's self-reported reason for abandoning the child's treatment since 2011.   Table 1. The age of children who experienced medical withdrawing was significantly higher than those who experienced premature withdrawing (median: 24 vs. 8 months, p < 0.001). There was significant difference in primary disease between children who experienced premature withdrawing and medical withdrawing (infectious proportion: 20.7 vs. 35.6%, p < 0.001). Table 1 Characteristic of children whose treatment was withdrawn The year-incidence curve is shown in Fig. 1A. The highest incidence of total withdrawing treatment (24.3%) and the highest incidence of premature withdrawing (20.6%) occurred in 2007. The incidence of total withdrawing treatment and premature withdrawing Reasons given by guardians for withdrawing treatment are shown in Table 2. Among the 326 children whose treatments were withdrawn in 2011-2017, "illness is too severe" ranked first, accounting for 66.3%, followed by "condition has been improved" (20.9%).
Almost all guardians (96.1%) of children who experienced medical withdrawing selfreported reason as "illness is too severe", a few guardians (3.9%) self-reported reason as "condition has been improved". For guardians of children who experienced premature withdrawing, these two reasons account for 46.7% and 32.0%, respectively. Of all guardians of children who experienced premature withdrawing, 7 (3.5%) guardians selfreported "economic reason", one (0.5%) guardians self-reported "unclear diagnosis". 3 Treatment modalities that were withdrawn.
The life-sustaining treatment modalities that were withdrawn are shown in Table 3. The most frequent modalities withdrawn were intravenous, ventilation and intubation. In 24% of cases, all three treatment modalities were withdrawn.

Discussion
Withdrawing treatment is not only a medical ethical issue, but a social issue. There has been considerable debate about how to implement withdrawal of treatment. Some scholars in China believe that withdrawal of treatment in ICUs should follow the principle of benefit and respect the patient's willingness and fairness principle [10]. People also believe that decisions on withholding/withdrawing treatment need to take account of the likely success, benefits, burdens and risks of treatment, as well as the patient's presumed wishes [4]. For children, however, withdrawing treatment is decided by their guardian(s), as children do not have full civil liability, and guardians' decisions are not always in the best interest of the child. Therefore, in this study we classified cases of withdrawing treatment into two categories: children who were unlikely to survive and whose treatment was withdrawn and children for whom a treatment was indicated but whose guardian(s) chose to abandon treatment.
For the treatment of children with severe illness in China, the general practice of physicians is to have a conversation with the child's guardian, introduce the child's condition to the guardian, provide medical advice, including whether or not it is worth administering a treatment, and discuss treatment methods and prognosis, after which the guardians are asked to make a decision. In many cases, even if a child has a chance to survive, their guardians choose to abandon treatment. When patients cannot articulate their wishes in American hospitals, it has been reported that ICU physicians and nurses usually leave final decisions in the hands of the families [11]. In the USA, physicians won't say in absolute terms whether a child will die or whether they will experience poor functional outcomes [12], and fear of litigation is a major barrier to properly informing a child's guardians in Greece [13]. From the results presented in this study-over the past decade in the PICU, there has been a decrease in incidence of withdrawing treatment and an increase in the age of children whose treatment was withdrawn-show that guardians are more willing to actively treat their children. It has been reported that guardians withholding or withdrawing intensive care for extremely preterm infants at the limits of viability has become more acceptable than it was 20 years ago in Germany, Switzerland, and Austria [18]. The incidence of withdrawing treatment in recent years in this study is similar to the incidence of withdrawing treatment of neonatal intensive care in Korea [19].  [21]. Other studies have also shown that per capita GDP has a high negative correlation with infant mortality in China [22].
In this study, more than one-half of the guardians stated that their reason for withdrawing treatment was that the child's condition was too severe. Only a few of the guardians ascribed withdrawing treatment to economic reasons, which is inconsistent with another study in which economic reasons accounted for one-half of the total [23]. This difference may be due to variations in the study method. Our medical documents only recorded guardians' self-reported reasons for treatment withdrawal, which may have introduced a bias. Children at the time of withdrawal of treatment had lower disease severity than at admission [23], and one in five guardians cited "condition has been improved" as a reason for withdrawing in this study, of most these guardians were guardians of children who experienced premature withdrawing. We suggest that this was not representative of the true reason for withdrawing treatment, guardians may have moderated their statements to alleviate their guilt. Under the influence of Chinese Confucian culture, guardians are used to the expression of compromise. We believe that the main reasons for premature abandonment may be related to economic status and uncertainty of prognosis. Children are often only covered by limited health insurance, and continuing treatment will incur a heavy economic burden. We observed another phenomenon that premature abandonment was rare in children raised in social welfare institutes, in large part because the treatment expenses of such children are ensured by the government.
Although death practices are changing in China, the idea of a death occurring at home or in the person's hometown, in the main hall in the presence of ancestor tablets is still cherished [3]. This may be one of the factors affecting the guardian's decision. The low proportion of deaths in hospital of children whose treatment was withdrawn prematurely and the fact that some children experiencing medical withdrawing survived when discharged from hospital may be influenced by the death culture in China. Similar practices can be observed elsewhere: home deaths for critically ill babies/children does occur in the UK, although infrequently [24]. When interpreting the results from this study, some limitations should be considered. This was a single center retrospective study. The region where the hospital is located is undergoing rapid urbanization, and is an economically developed region in China. The results of this study are not representative of all of China. The impact of culture, healthcare insurance status, religion and education on the withdrawal of treatment has not been studied.

Conclusions
The decreasing in incidence of withdrawing treatment and an increase in the age of children whose treatment was withdrawn show that guardians are more willing to actively Helsinki declaration and its later amendments or comparable ethical standards. All participants were enrolled following written informed consent given by their parents and the permission to access patient data was obtained from the health facility. Data on the condition of the child and the withdrawn treatment were collected from the informed consent form and the doctor-patient records. These documents also recorded the guardian's self-reported reason for abandoning the child's treatment since 2011. The use of this data was approved by the ethics committee.

6) Consent for publication
Not applicable.

7) Competing interests
The authors declare that they have no conflict of interest.   The median age of children whose treatment was withdrawn during 2006-2017.