2.1 demographic characteristics of group A and B
Between January 2012 and November 2019, 80 children were admitted to the Department of Palliative Medicine, West China Fourth Hospital, of whom 41 died during their hospitalisation. There were 24 in the palliative sedation group (Group A) and 17 in the non-palliative sedation group (Group B). The demographic characteristics of the two groups are shown in Table 1. The differences between the two groups were not statistically significant.
Table 1
Demographic characteristics of palliative sedation and non-palliative sedation groups in children
Demographic characteristics (N=41)
|
Group A
(n=24)
|
Group B
(n=17)
|
p
|
Age
|
|
|
|
0-28 days
|
0
|
3
|
0.228&
|
29 days -1 year
|
3
|
1
|
|
2-6 years
|
11
|
6
|
|
7-18 years
|
10
|
7
|
|
Gender
|
|
|
|
Male
|
15
|
13
|
0.40&
|
Female
|
9
|
4
|
|
Type of disease
|
|
|
|
Blood tumor
|
4
|
3
|
0.564&
|
Solid tumor
|
16
|
8
|
|
Congenital disease
|
2
|
3
|
|
Diseases of the blood system
|
0
|
1
|
|
Severe infection
|
2
|
2
|
|
Hydration during hospitalization
|
21
|
14
|
0.679&
|
&Fisher of the exact probability method
|
2.2 Symptoms
The main symptoms were pain, dyspnea, irritability, fever, coma, vomiting, convulsions (see figure 1). Pain occurring in 28/41(68%) children was the most common symptom affecting the children’s quality of survival at the end of life. Four children in group A got four types of symptoms, ten children got three types, seven children got two types and three children with one symptom. None children got four symptoms in group B, four children got three symptoms, three got two symptoms and ten got one symptom. Distribution of symptoms in two groups see in Table 2.Types of symptoms differed between the two groups, p =0.013. The symptoms in group A were more complex than those in group B. But overall symptom relief was higher in A Group which used sedative medication (p=0.041). Five patients in Group B whose symptoms remained unrelieved were fever, abdominal distension, and dyspnea. Three of five were non-tumor. Pain control rate was similarities between the two groups, 95.23% and 100% respectively.
Table 2
Types and relief of symptoms in Group A and B
|
|
Type of symptom (s)
|
|
Symptom control
|
Pain control
|
|
n
|
1
|
2
|
3
|
4
|
n
|
No remission
|
remission
|
Obvious remission
|
n
|
No remission
|
Mild remission
|
Moderate remissions
|
Obvious remissions
|
Group A
|
24
|
3
|
7
|
10
|
4
|
24
|
0
|
20
|
4
|
21b
|
1c
|
2
|
16
|
2
|
Group B
|
17
|
10
|
3
|
4
|
0
|
15a
|
5
|
8
|
2
|
7b
|
0
|
2
|
4
|
1
|
Z
|
|
-
|
|
2.045
|
|
0.367
|
p
|
0.013d
|
|
0.041e
|
|
0.714 e
|
a. 2 cases of coma excluded from 17, were not included in the assessment. |
b. There were no analgesia in 3 cases of Group A and 10 cases of Group B. |
c. too short hospital stay to evaluated. |
d. the exact probability method. |
e. rank sum test. |
2.3 Pain control
Twenty-one children in Group A used analgesic; besides three patients of Group A were not prescribed for analgesia because the main symptoms were convulsions and moans. In beginning, four children had been prescribed two types of analgesics at the same time, such as hydrocodone sustained-release tablets, acetaminophen and hydrocodone, morphine sulfate solution combined with continuous venous morphine by syringe driver, fentanyl transdermal combined with morphine sulfate solution. The other 16 patients received hydrochloride morphine continuous venous infusion and 1 patient used morphine sulfate oral solution alone. 7 children in group B used analgesic (7/17 cases who got fever, coma were not prescribed analgesic, and 3/17 cases who prescribed morphine only beacause of dyspnea were not included in pain assessment). In group B one child used hydrocodone sustained-release tablets, six used morphine continuous venous infusion. Pain scores on admission and after control were higher in group A than in group B (p =0.014, 0.039), but there was no significant difference in maximum opioid dosage and pre-death opioid dosage between the two groups. Pain control is shown in Table 3.
Table 3
Pain control in Group A and B
|
N
|
Admission
|
After symptom control
|
Maximum opioid dose converted to oral morphine dosage/24 hours
(mg)
|
Opioid dose before death converted to oral morphine dosage /24 hours
(mg)
|
Pain intensity difference
|
Pain score
|
Pain duration
(hours)
|
Sleep
(hours)
|
Pain score
|
Pain duration
(hours)
|
Sleep
(hours)
|
Group A
|
21
|
8(7,10)
|
24(20,24)
|
6(4,7)
|
3(3,4)
|
4(2.5,7)
|
8(6,10.5)
|
30(20,77.5)
|
30(20,60)
|
5(4,6.5)
|
Group B
|
7
|
7(6,7)
|
22(18,24)
|
4(4,5.5)
|
2(0,3)
|
4(1.5,13)
|
9(8,-)
|
18(9,45)
|
18(9,45)
|
4(2,6)
|
Z
|
|
-2.501
|
-0.095
|
-1.481
|
-2.068
|
-0.065
|
0.615
|
-1.358
|
-1.278
|
-1.004
|
p
|
|
0.014
|
0.924
|
0.139
|
0.039
|
0.948
|
0.538
|
0.175
|
0.208
|
0.315
|
Opioids were the first choice for moderate and severe pain in children at the end of life. In our study, before hospital admission 24 children were treated with morphine sulfate/hydrochloride, 2 with oxycodone hydrochloride, 1 with fentanyl and 1 with acetaminophen and hydrocodone mixture. The forms included sustained-release tablets, oral liquid, injection, and transdermal patches. Two children were treated with two types of opioids (morphine sulfate oral solution + morphine hydrochloride injection, fentanyl transdermal patch + morphine sulfate oral solution). Sixteen cases only used single opioid analgesia, 12 cases used 1-3 adjuvant analgesic drugs, including paracetamol, ketorolac trometamol, scopolamine butyrate, gabapentin capsule, valproate sodium, and ketamine.
2.4 Dyspnea
In the study, twelve children had dyspnea, aged 4 days to 14 years. Three patients had dyspnea as single symptom, and other nine combined with pain, irritability, fever, and other symptoms. There were six cases in Group A and six cases in Group B. Both groups had 83% remission of dyspnea. Both groups used morphine to relieve dyspnea. The survival time and the hospitalization time of the two groups were shown in Table 4(The data are non-normal, expressed in quartile spacing). The sample size of children with dyspnea was too small to analyze.
Table 4
Relief rate and survival time of dyspnea patients in Group A and Group B
|
n
|
dyspnea relief rate
%(n)
|
Survival time after diagnosis of diseasea
(days)
|
Hospitalization timea
(days)
|
Group A
|
6
|
83%(5)
|
450 (253.5,1036.5)
|
7.5(1,21.5)
|
Group B
|
6
|
83%(5)
|
63.5(52.5,1855)
|
12(1.75,51.75)
|
a. quartile spacing |
2.5 Duration of survival and hospitalization time after diagnosis in Group A and Group B.
The survival time after diagnosis in Group A was 20 days - 2190 days and hospitalization time was 1-85 days. The duration of survival in Group B was 5 days - 5475 days and the length of stay in hospital was 1 - 63 days (see Table 5). Longer survival time after disease diagnosis in group A compared to group B (p = 0.047). However, the hospitalization time before death was similar. Palliative sedation treatment seemed not shorten the hospitalization time of children at the end of life.
Table 5
Survival time after diagnosis and hospitalization time before death in Group A and Group B
|
Survival time after diagnosis of disease
|
Last hospitalization
|
Group A
|
365(112.5,730)
|
9(2.5,22.75)
|
Group B
|
60(30,795)
|
3(1,24)
|
Z
|
-1.987
|
-0.869
|
p
|
0.047
|
0.385
|
2.6. Sedation in Group A
In electronic records, children(age from 5 months to14 years, 15 males, 4 blood tumors, 16 solid tumors, 2 Congenital diseases, 2 infection, were prescribed sedation drugs. There were one to four main symptoms types (pain, dyspnea, irritability, fever, coma, vomiting, convulsions). Palliative sedation was mainly caused by irritability in 13 cases, convulsion in 5 cases, pain in 7 cases, and dyspnea in 6 cases. Midazolam was used in 17 cases; chlorpromazine was used in 1 case. Six cases used midazolam combined with chlorpromazine. The hospital stays lasted from 1 hour to 85 days, and the use of sedatives lasted from 1 hour to 47 days. The purpose of sedation was to reduce consciousness to control painful symptoms. Before and after sedation, the average Ramsay score was 1(1, 1) and 2(2, 3). When death was coming, the deeper sedation score was observed 3(2, 4)(p <0.01)(see Table 6). Beginning of the sedation, the initial dose of midazolam ranged between 0.5 - 5 mg/24 hours [mean 1.5(1, 2.4) mg/24h]. Maximum dose was 0.5-30 mg/24 hours [mean 3(1,6)mg/24h], and the pre-death dose was 0.5-25 mg/24 h [mean 3(1,5)mg/24h]. The maximum dosage of midazolam was similar to that before death( p =0.066). In 4 cases, midazolam was down regulated before death for unknown reasons, but the degree of sedation was not reduced. Midazolam sedation duration did not appear to be associated with maximum dose and pre-death does.
Table 6
Ramsay scores of sedation group
|
Ramsay score a
|
Pre- sedation score
|
1(1,1)
|
Sedation score after symptom control
|
2(2,3)
|
Pre-death sedation score
|
3(2,4)
|
Χ 2
|
34.344
|
P b
|
<0.01
|
a. percentile spacing, |
b. Friedman Inspection |