Patient demographics:
We received data from eight PCCUs across the UK for 96 admissions during the study period. Of the 96 admissions, 91 had complete data for guideline used and were therefore included in the analysis comparing the two guidelines. The overall median age of children admitted to PCCU was 9 years (IQR: 4-12.5) with slightly more boys (55%). Overall median weight on admission was 30kg (IQR = 16.5–43.9). Weight was measured in 48 cases, estimated in 39 cases and the method for determining weight was unknown for nine patients. There was equal distribution of patients transferred from a District General Hospital and those admitted from the same Tertiary Hospital and equal numbers presenting in-hours and out-of-hours. Out of the 96 admissions to PCCU, 84% were new diagnoses of T1DM whilst 16% had a known diagnosis of T1DM. There were higher number of admissions in the months of December, January, and July (Fig. 1). Overall median pH at initial presentation was 6.9, HCO3 was 6.0 mmol/L, blood glucose = 32.0 mmol/L and blood ketones = 5.6 mmol/L. Corrected sodium was calculated for 42% of patients.
Differences between liberal and restrictive fluid groups:
Of the 91 included admissions, 30 adhered to the liberal fluid guidance and 32 patients were treated following restrictive fluid guidance. 29 patients were managed according to LCPs. Patient demographics and biochemical profile at initial presentation, by guidance followed are presented in Table 1.
Table 1
Patient demographics and biochemical profile at initial presentation for patients, by BSPED guidelines followed (2009 & 2015)
|
Liberal Fluid
n = 30 (33%)
|
Restrictive Fluid
n = 32 (35%)
|
X2*/z†
|
(p value)
|
Age (years)
|
10 (2–13)
|
9 (5.5–12.5)
|
0.007
|
0.994
|
Weight on admission (kg)
|
32 (14–40)
|
30 (19–45)
|
-0.303
|
0.762
|
Sex (Males)
|
18 (59%)
|
16 (48%)
|
0.625
|
0.429
|
Out of hours presentation
|
14 (47%)
|
16 (50%)
|
0.007
|
0.793
|
Admission from same hospital
|
13 (43%)
|
21 (66%)
|
3.107
|
0.078
|
New diagnosis of diabetes mellitus
|
28 (93%)
|
24 (75%)
|
3.847
|
0.050
|
pH
|
6.9 (6.8-7.0)
|
6.9 (6.9-7.0)
|
-0.070
|
0.944
|
pCO2 (kPA)
|
2.5 (1.7–2.9)
|
2.8 (2.0-3.5)
|
-1.256
|
0.209
|
HCO3 (mmol/L)
|
5.2 (4.0-6.8)
|
5.7 (2.9–7.8)
|
-0.363
|
0.716
|
Lactate (mmol/L)
|
2.3 (1.8–3.2)
|
2.5 (2.1–3.3)
|
-1.178
|
0.239
|
Glucose (mmol/L)
|
35(27–48)
|
28 (24–39)
|
1.775
|
0.076
|
Sodium (mmol/L)
|
137 (131–141)
|
136 (131–141)
|
0.621
|
0.535
|
Corrected Sodium (mmol/L)
|
150 (144–158)
|
143 (141–146)
|
2.499
|
0.013
|
Creatinine (mmol/L)
|
75 (34–121)
|
66 (45.5–89.5)
|
0.838
|
0.402
|
Potassium (mmol/L)
|
4.7 (4.2–5.2)
|
4.1 (3.7–4.9)
|
1.742
|
0.082
|
Urea (mmol/L)
|
7.9 (6.3–12.7)
|
6.5 (4.7–9.8)
|
1.789
|
0.074
|
Blood Ketones (mmol/L)
|
5.0 (4.5–5.5)
|
5.5 (4.7–6.1)
|
-0.944
|
0.345
|
Glasgow Coma Scale (GCS) on presentation
|
14 (10–15)
|
13 (11–15)
|
-0.278
|
0.781
|
Continuous variables presented as median (interquartile range) and categorical variables presented as (n, (%)). |
*Results of a Mann-Whitney U (Wilcoxon rank sum) test for continuous variables, in turn, by guidelines followed (2009 vs 2015). |
†Results of a chi-square test of independence comparing differences in frequency count distributions of categorical variables in turn, by guidelines followed (2009 vs 2015). Where results are significant (p < = 0.05), corresponding X2/z values are reported. |
A higher proportion of patients were non-compliant for estimation of dehydration in the restrictive fluid group, 15% (n = 5) vs 7% (n = 2) in the liberal fluid group. 44% (n = 14) in restrictive group received more resuscitation fluid than advised whereas 20% (n = 6) of patients in the liberal group received initial fluid boluses which exceeded the recommended volume.
Factors affecting compliance with the BSPED guidance included transfer from another hospital, higher urea on admission, and lower GCS on initial presentation. Overall, patients who were non-compliant with the guidance received higher volume of fluid boluses on initial presentation and during the first 24 hours of admission. (Table 2)
Table 2
Patient factors affecting compliance to BSPED guidelines (2009 & 2015)
|
Liberal Fluid (BSPED 2009)
n = 30
|
Restrictive Fluid (BSPED 2015)
n = 32
|
|
Compliant
n = 22 (73%)
|
Non-compliant
n = 8 (27%)
|
Compliant
n = 18 (56%)
|
Non-compliant
n = 14 (44%)
|
Factors affecting compliance
|
|
|
|
|
pH
|
6.9 (6.8-7.0)
|
6.9 (6.8–6.9)
|
7.0 (6.9-7.0)
|
6.9 (6.8-7.0)
|
Urea (mmol/L)
|
7.3 (6.2–10.7)
|
8.4 (7.6–14.4)
|
5.6 (4.6–7.4)
|
8.4 (5.5–12.7)
|
Glasgow Coma Score on presentation
|
14 (10–15)
|
13 (5–14)
|
14 (13–15)
|
13 (9-14.5)
|
Out of hours presentation
|
9 (42.9)
|
5 (62.5)
|
8 (47.1)
|
7 (50.0)
|
Admission from same hospital
|
11 (52.4)
|
2 (25.0)
|
14 (82.4)
|
6 (42.9)
|
Fluid variables
|
|
|
|
|
Volume of initial fluid bolus (ml/kg)
|
20 (10–30)
|
35.9 (28–241)
|
10 (2–10)
|
20 (20–50)
|
Fluid boluses in 24 hrs (ml/kg)
|
25 (10–30)
|
33.9 (22.5-242.5)
|
10 (5–17)
|
35 (20–45)
|
Patients in the liberal fluid group received more resuscitation fluid as boluses on initial presentation (median: 20ml/kg, IQR: 20–30) compared to those in restrictive group (median: 10ml/kg, IQR: 9.6–20). Total amount of fluid received in the first 24 hours since initial presentation was also higher in the liberal group (median: 108ml/kg, IQR: 92–122) than the restrictive group (median: 82ml/kg, IQR: 70–95). (Table 3)
Table 3
Management and clinical outcomes of patients on paediatric critical care units (PCCU) by BSPED guidelines followed (2009 & 2015)
|
BSPED 2009
n = 30 (33%)
|
BSPED 2015
n = 32 (36%)
|
z*
|
p value
|
|
Management
|
|
|
|
|
|
Time to PCCU admission (hours)
|
8.3 (4.6–23.1)
|
6.2 (4-10.3)
|
0.740
|
0.459
|
|
Total amount of fluid in 24 hrs since initial presentation (ml/kg)
|
108 (92–122)
|
82 (70–95)
|
0.552
|
0.581
|
|
Total amount of fluid in 24–48 hrs (ml/kg)
|
79 (74–97)
|
74 (60–84)
|
0.228
|
0.774
|
|
Total amount of fluid boluses on initial presentation (ml/kg)
|
20 (20–30)
|
10 (9.6–20)
|
2.514
|
0.012
|
|
Total amount of fluid boluses in 24 hrs since initial presentation (ml/kg)
|
30 (20–37)
|
17 (10–35)
|
1.942
|
0.052
|
|
Length of stay in PCCU (days)
|
2 (2–3)
|
2 (1.5-4)
|
-0.037
|
0.971
|
|
Highest Urea (mmol/L)
|
8.6 (7-13.8)
|
8.5 (5-12.5)
|
0.775
|
0.438
|
|
Time to starting insulin from initial presentation (hours)
|
2.2 (1.6–3.2)
|
2.4 (2–3)
|
-0.575
|
0.565
|
|
Clinical outcomes
|
|
|
X2†
|
p value
|
OR (95%CI)1
|
Survived to discharge
|
30 (%)
|
30 (93.8%)
|
1.94
|
0.164
|
-
|
Fluid readjusted on admission to PCCU
|
18 (72%)
|
14 (45%)
|
4.00
|
0.045
|
0.32 (0.09–1.04)
|
Diagnosed with cerebral oedema
|
11 (37%)
|
16 (50%)
|
1.10
|
0.294
|
1.72 (0.61–4.85)
|
|
Treated for cerebral oedema2
|
11 (100%)
|
15 (94%)
|
0.65
|
0.420
|
-
|
Renal Replacement therapy
|
6 (21%)
|
2 (6%)
|
2.56
|
0.109
|
0.27 (0.04–1.52)
|
Mechanical ventilation
|
8 (26.7%)
|
8 (25.0%)
|
0.02
|
0.881
|
0.91 (0.29–2.89)
|
Vasoactive agents used
|
1 (3%)
|
1 (3%)
|
0.00
|
0.962
|
0.93 (0.05–16.02)
|
Inotropic support received
|
6 (20%)
|
7 (22%)
|
0.03
|
0.861
|
1.12 (0.32–3.85)
|
Continuous variables presented tab as median (interquartile range) and categorical variables presented as (n, (%)). |
*Results of a Mann-Whitney U (Wilcoxon rank sum) test for continuous variables, in turn, by guidelines followed (2009 vs 2015). |
†Results of a chi-square test of homogeneity of odds comparing the 2015 group to 2009 group. |
1 Odds ratios for incidence of each clinical outcome, for 2015 compared to 2009 group and corresponding 95% confidence interval. |
2 Of those diagnosed with cerebral oedema in each group. |
There was no difference in highest urea noted during admission and the median length of PCCU admission was 2 days in both groups. There were fewer patients in liberal fluid group (37%, n = 11) with clinical diagnosis of cerebral oedema than in the restrictive group (50%, n = 16). A higher number of patients in liberal group received renal replacement therapy and the proportions of patients who received mechanical ventilation and vasoactive support were similar between the two groups (Table 3).
The two patients, who did not survive to discharge, both adhered to the restrictive fluid guidance. On further detailed review of these cases, one of them was clinically suspected to be in septic shock at presentation with pupillary changes and an initial CT head showing signs of cerebral oedema. The patient developed multi-organ failure and also received renal replacement therapy. The second patient had signs of cerebral oedema on initial presentation and died secondary to brainstem involvement.
Cerebral Oedema:
Among all admissions to PCCU, 42% (n = 40/96) were suspected to have cerebral oedema at some point during their admission. The clinical suspicion for cerebral oedema was based on dropping GCS in 90% (n = 36/40) of these cases. Out of these patients, clinical seizures, abnormal pupils, and bradycardia with hypertension were reported for one case each. Cerebral oedema was diagnosed because of developing clinical seizures in one case and the reason for diagnosis of cerebral oedema was unknown in three cases.
Of the 40 admissions who had a clinical diagnosis of cerebral oedema, 85% (n = 34) underwent neuro-radiological imaging with findings suggestive of cerebral oedema in 15% (n = 5) of these cases. Pharmacological interventions such as intravenous mannitol and hypertonic saline were used for 85% (n = 34) of cases of suspected cerebral oedema. Children suspected to have cerebral oedema were older than those without suspicion of cerebral oedema and 77% (n = 31) were newly diagnosed with T1DM at this presentation. The demographic characteristics and biochemical profiles of patients with and without a clinical diagnosis of cerebral oedema, respectively, are summarised in Table 4.
Table 4
Demographic and biochemical profile and fluid boluses for patients with and without a recorded clinical diagnosis of cerebral oedema during single PCCU admission.
|
Diagnosis of Cerebral Oedema During PCCU Admission
|
|
|
|
Clinical diagnosis of cerebral oedema
n = 40 (42%)
|
No recorded diagnosis of cerebral oedema
n = 56 (58%)
|
X2*/z†
|
p value
|
Age (years)
|
12 (9.5–14)
|
6 (1-10.5)
|
-4.417
|
< 0.001
|
Sex (Males)
|
18 (45%)
|
35 (62.5%)
|
5.135
|
0.023
|
Ketones (mmol/L)
|
5.6 (4.7–6.5)
|
5.6 (4.8–6.1)
|
0.747
|
0.455
|
Glucose (mmol/L)
|
33 (27–44)
|
31 (25–37)
|
-1.113
|
0.183
|
pCO2 (kPA)
|
3.0 (2.3–3.7)
|
2.7 (2-3.5)
|
-1.888
|
0.059
|
HCO3
|
6 (4.0-7.2)
|
6.5 (4.4–7.9)
|
0.448
|
0.654
|
pH
|
6.9 (6.8-7.0)
|
7.0 (6.9–7.1)
|
2.958
|
0.003
|
Urea
|
9.2 (6.0-14.1)
|
6.4 (5.4–8.4)
|
-2.949
|
0.002
|
Sodium (mmol/L)
|
136 (129–141)
|
136 (132–140)
|
1.089
|
0.276
|
Corrected Sodium (mmol/L)
|
150 (144–153)
|
145 (141–150)
|
-0.680
|
0.497
|
Volume of initial fluid bolus (ml/kg)
|
20 (17–40)
|
20 (10-27.5)
|
-1.438
|
0.151
|
Fluid boluses in 24 hrs (ml/kg)
|
27 (20–50)
|
20 (10–30)
|
-2.299
|
0.022
|
New diagnosis of diabetes mellitus
|
31 (77.5%)
|
50 (89%)
|
6.690
|
0.010
|
Admission from same hospital
|
13 (32.5%)
|
31 (55.4%)
|
7.890
|
0.003
|
Continuous variables presented as median (interquartile range) and categorical variables presented as (n, (%)). |
*Results of a Mann-Whitney U (Wilcoxon rank sum) test for continuous variables, in turn, by guidelines followed (2009 vs 2015). |
†Results of a chi-square test of homogeneity of odds comparing the 2015 group to 2009 group. |
P value to be considered significant if < 0.03 |
Univariate logistic regression analyses showed significant associations with increasing age (Coef: 0.25, 95% CI: 0.14–0.37, p < 0.001), transfer from a different hospital (OR: 0.39, 95% CI: 0.17–0.90, p = 0.030) and serum urea on initial presentation (Coef: 0.15, 95% CI: 0.06–0.26, p = 0.002), in turn, on risk of cerebral oedema. When these variables were modelled in an adjusted, multivariate model, only serum urea (Coef: 0.18, 95%CI: 0.04–0.30, p = 0.010) and age on admission ( Coef: 0.24, 95%CI: 0.12–0.37, p < 0.001)) remained significantly associated with risk of cerebral oedema.