ONLINE CLINICAL INVESTIGATIONS

Lactate, Base Excess, and the Pediatric

Index of Mortality: Exploratory Study
of an International, Multicenter Dataset
Kevin P. Morris, MD1,2
OBJECTIVES: To investigate the relationship between ICU admission blood lac- Melpo Kapetanstrataki, MSc3
tate, base excess, and ICU mortality and to explore the effect of incorporating
Barry Wilkins, MD4
blood lactate into the Pediatric Index of Mortality.
Anthony J. Slater, MD5
DESIGN: Retrospective cohort study based on data prospectively collected
Victoria Ward, MD4
on every PICU admission submitted to the U.K. Pediatric Intensive Care Audit
Network and to the Australia and New Zealand Pediatric Intensive Care Registry. Roger C. Parslow, PhD3

SETTING: Thirty-three PICUs in the United Kingdom/Republic of Ireland and

nine PICUs and 20 general ICUs in Australia and New Zealand.
PATIENTS: All ICU admissions between January 1, 2012, and December 31, 2015.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: One hundred twenty-three thou-
sand two hundred fifty-two admissions were recorded in both datasets; 81,576
(66.2%) in the United Kingdom/Republic of Ireland and 41,676 (33.8%) in
Australia and New Zealand. Of these 75,070 (61%) had a base excess recorded,
63,316 (51%) had a lactate recorded, and 60,876 (49%) had both base excess
and lactate recorded. Median lactate value was 1.5 mmol/L (interquartile range,
1–2.4 mmol/L) (United Kingdom/Republic of Ireland: 1.5 [1–2.5]; Australia and
New Zealand: 1.4 [1–2.3]). Children with a lactate recorded had a higher ill-
ness severity, were more likely to be invasively ventilated, admitted after cardiac
surgery, and had a higher mortality rate, compared with admissions with no lac-
tate recorded (p < 0.001). The relationship between lactate and mortality was
stronger (odds ratio, 1.32; 95% CI, 1.31–1.34) than between absolute base ex-
cess and mortality (odds ratio, 1.13; 95% CI, 1.12–1.14). Addition of lactate to
the Pediatric Index of Mortality score led to a small improvement in performance
over addition of absolute base excess, whereas adding both lactate and absolute
base excess achieved the best performance.
CONCLUSIONS: At PICU admission, blood lactate is more strongly associated
with ICU mortality than absolute base excess. Adding lactate into the Pediatric
Index of Mortality model may result in a small improvement in performance. Any
improvement in Pediatric Index of Mortality performance must be balanced against
the added burden of data capture when considering potential incorporation into
the Pediatric Index of Mortality model.
KEY WORDS: base excess; lactate; mortality prediction; Pediatric Index of
Mortality; severity of illness

M
ortality risk prediction is central to case-mix adjustment and assess- Copyright © 2022 by the Society of
ment of ICU performance. Two scoring systems are used widely Critical Care Medicine and the World
in pediatric practice—the Pediatric Index of Mortality (PIM), first Federation of Pediatric Intensive and
published in 1997 (1), and the Pediatric Risk of Mortality Score (PRISM), Critical Care Societies
first published in 1988 (2). In the latest versions, PIM3 adjusts for admitting DOI: 10.1097/PCC.0000000000002904

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Unauthorized reproduction of this article is prohibited

diagnosis, type of admission, and various physiologic
variables over the first hour of ICU admission (3),
whereas PRISM III includes the most abnormal values
of a number of prespecified physiologic and labora-
tory variables over the first 4 hours of admission (4).
Each score incorporates a marker of acid-base status:
pH for PRISM III and “absolute” base excess (BE) for
PIM3, reflecting the fact that in the development of
PIM, both a positive BE and a negative BE were associ-
ated with greater mortality risk. The PIM3 score is the
scoring system used to compare PICU performance
across the United Kingdom and Republic of Ireland,
and Australia and New Zealand (ANZ).
Monitoring of blood lactate was not common prac-
tice in ICUs at the time that PRISM and PIM scores
were derived, and so its performance was not evalu-
ated in their development, nor evaluated in subsequent
revisions. However, since the scores were developed,
a large body of literature has emerged supporting a
strong relationship between blood lactate and mor-
tality in neonatal, pediatric, and adult critically ill
patients (5–9). A recent study in adults with sepsis
found lactate to be a more powerful predictor than
even refractory hypotension (10). A number of these
studies have highlighted the superior predictive power
of blood lactate over other acid-base markers, specifi-
cally pH and BE (6, 7).
Many different factors can affect blood lactate con-
centration, and our understanding has moved on be-
yond simple interpretation of lactate as a marker of
anaerobic metabolism in situations of hypoperfu-
sion; both the rate of production and of clearance,
particularly in the liver and kidney, will influence the
level (11). Clearance is often compromised in the crit-
ically ill (12). In addition, situations which result in an
increase in glucose metabolism (glycolysis) will result
in increased lactate generation, in the absence of anaer-
obic metabolism or hypoperfusion. Drugs, including
epinephrine and salbutamol, have this effect (13).
Hyperventilation-induced alkalosis can also result
in an increase in blood lactate concentration (14). Not
all of these clinical situations would be expected to be
associated with increased mortality. In keeping with
this complexity, the relationship between blood lac-
tate concentration and markers of acidosis (pH, bicar-
bonate, BE) is not a simple one, and there may not be
a tight relationship between lactate concentration and
pH or BE (15).
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Online Clinical Investigations
Single-center studies have suggested that inclusion
of blood lactate results in improved performance of
PIM2 (6) and PRISM III (16). Point-of-care measure-
ment of blood lactate is now available using blood gas
analysers, and lactate has been incorporated into key
pediatric and adult ICU guidelines (17–19), and in
many ICUs is now monitored as standard ICU practice.
In this study, we combine two large international
PICU databases from the United Kingdom and
Republic of Ireland (ROI) and ANZ to investigate
relationships between blood lactate, BE, and ICU
mortality. In addition, we explore the effect of incor-
porating blood lactate into PIM and consider how best
to deal with missing values.
MATERIALS AND METHODS
Study Population and Study Design
This was a retrospective cohort study based on data
prospectively collected on PICU admission. BE and
lactate measurements were all taken in the time pe-
riod between first contact with an ICU doctor and 1
hour after ICU admission. All admissions between
January 1, 2012, and December 31, 2015, were in-
cluded. Data were obtained from the Pediatric
Intensive Care Audit Network (PICANet) (20) and
the Australian and New Zealand Pediatric Intensive
Care (ANZPIC) Registry (21). PICANet is an audit
database, established in 2002, which collects de-
tailed information on all children admitted to 33
designated PICUs in the United Kingdom and the
ROI. Collection of personally identifiable data was
approved by the Patient Information Advisory Group
(now the Health Research Authority Confidentiality
Advisory Group), and ethical approval for the use of
data for research purposes was granted by the Trent
Medical Research Ethics Committee (REC 2018/
EM/0267). The ANZPIC registry was established
in 1997 and contains information on all admissions
to nine PICUs as well as 20 general ICUs in ANZ.
Ethical approval for maintaining the registry and
using the data for research and quality improvement
was granted by the Children’s Health Queensland
Hospital and Health Service Human Research Ethics
Committee (HREC/2016/QRCH/338). This study,
using retrospective data, was undertaken in accord-
ance with the above Ethics/IRB approvals. No per-
sonally identifiable data were used.
 Morris et al

A series of analyses were undertaken which are
summarized in Figure 1 and described in detail below.
Analysis 1—Descriptive Statistics
All admissions were included in this analysis which
examined the characteristics of patients with and
without a lactate value obtained at ICU admission.
Normality of continuous variables was assessed with
the use of histograms and the Shapiro-Wilk statistic.
Association between the availability of a lactate value
(yes/no) and continuous variables was investigated
with the use of the nonparametric Mann-Whitney U
test and between categorical variables with the chi-
square test.
Analysis 2—Relationship Between Lactate,
BE, and Mortality
This analysis was confined to admissions with both
lactate and BE values obtained at ICU admission.
Arterial, capillary, and venous BE and lactate values
were included. Correlation between lactate and BE was
assessed with the Spearman correlation coefficient.
Generalized additive modeling (GAM) functions were
used to visualize the trend of mortality against lactate
and BE values. A generalized additive model is a gen-
eralized linear model in which smoothing functions
of the linear predictors are used instead. The smooth-
ing function used was based on penalized regression
splines.
Odds ratios (ORs) and 95% CI were calculated to
determine the risk of mortality per unit change in lac-
tate and BE. In addition, standardized ORs (sORs)
were calculated to assess the effect on mortality of an
increase of 1 sd in lactate and BE.
Analysis 3—Investigating Different Approaches
for Missing Lactate Values
In order to assess how best to handle missing lactate
values in subsequent modeling, we modified PIM2 by
substituting lactate for absolute BE, whenever lactate
was available, and assessed the impact on model perfor-
mance, measured by area under the receiver operating
characteristic curve (AUROC) and Akaike informa-
tion criterion (AIC). Three models were explored: 1)
setting missing lactate to 0, 2) setting missing lactate to
1, and 3) setting missing lactate to 1, replacing values
between 0 and less than 1 with the value 1 and using

Figure 1. Flow diagram describing analyses and numbers of admissions.

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the term (lactate–1) in the model. Missing BE was han-
dled according to established PIM guidance, substitut-
ing a value of zero.
Analysis 4—Evaluating PIM Performance Using
Absolute BE, Lactate, or Both Variables
PIM2 was introduced in 2003; therefore, PIM2 data
were available for the whole period of our study. Since
we had a large amount of data on PIM2, we recalibrated
it to more accurately represent the data and predict
mortality. PIM3 was introduced in 2013 but data collec-
tion did not start immediately, so complete PIM3 data
were available only for admissions in 2015. PIM3 was
not recalibrated, since we only had 1 year’s worth of data
and so it was appropriate to use the original coefficients.
A modified PIM model was created without BE, and
the impact on model performance of stepwise addition
of absolute BE alone, lactate alone, and a combination of
absolute BE and lactate was assessed. The analysis was
performed for both PIM2 (whole cohort) and PIM3
(2015 only) models. As per PIM guidance, a missing
BE was assigned a value of zero. Handling of missing
lactate was determined by the findings of Analysis 3.
The fit of the models was assessed with the use of the
AUROC, AIC, and the calculation of residuals and in-
fluence measures (Pearson, standardized Pearson and
Deviance Residuals, change in chi-square, change in de-
viance, and Pregibon Delta-Beta). Calibration plots were
created to visualize how well the predicted mortality
probabilities compared with the observed mortality. The
Hosmer-Lemeshow goodness of fit statistic was used,
grouping the patients in 20 groups according to their
estimated probability of mortality and then plotting the
observed against the predicted mortality of these groups.
Analysis with the use of the GAM functions was carried
out in RStudio 0.99.486 (R Foundation for Statistical
Computing, Vienna, Austria). All other analyses were
conducted in Stata 14.1 (StataCorp, College Station, TX).
Additional Analysis
Historically, PIM guidance has been to exclude BE
values derived from a venous sample. An analysis was
undertaken to explore and compare the performance
of PIM with and without venous BE values using the
ANZPIC registry cases only, since submission of ve-
nous BE values was supported in the ANZPIC registry
but not in PICANet.
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Online Clinical Investigations
RESULTS
In years 2012–2015, there were a total of 123,252
admissions recorded in both datasets; 81,576 (66.2%)
in the UK/ROI and 41,676 in ANZ (33.8%). Of these,
75,070 (61%) had a BE recorded, and 63,316 (51%) had
a lactate recorded. Of note the percentage with lactate
recorded increased from 47% in 2012 to 61% in 2015,
whereas the proportion with a BE recorded remained
constant. Lactate measurements of less than or equal
to 0 or greater than equal to 30 mmol/L (n = 7) were
recoded as missing.
Within the cohort of 63,316 admissions with an
admission lactate, there were 2,440 with no corre-
sponding BE value, leaving a cohort of 60,876 admis-
sions with both lactate and BE available (66.9% from
UK/ROI, 33.1% from ANZ) (Fig. 1).
Analysis 1 (n = 123,252)
Median lactate value was 1.5 mmol/L (interquartile
range, 1–2.4 mmol/L) (UK/ROI: 1.5 [1–2.5]; ANZ:
1.4 [1–2.3]). Table 1 shows descriptive characteristics
for children with and without a lactate measurement.
Median length of stay for children with a lactate meas-
urement was 2.26 days, compared with 1.74 days for
children without a lactate measurement (p < 0.001).
Children with a valid lactate measurement had a
higher illness severity based on PIM2 score, were more
likely to be invasively ventilated, admitted after cardiac
surgery (p < 0.001), and had a higher mortality rate
(4% vs 2.5%; OR, 1.57 [1.47–1.67]; p < 0.001).
Analysis 2 (n = 60,876)
The relationship between lactate, actual, and absolute
BE is shown in Figure 2, for the subset of cases with
a lactate and BE measurement. Overall the relation-
ship is relatively weak but stronger between lactate and
negative BE (rho = –23; p < 0.001) than positive BE
(rho = 0.008; p = 0.03).
Figures 3 and 4 show the relationship between lac-
tate, BE, and mortality, for the subset of cases with a
lactate and BE measurement, with the use of GAM
models. Negative BE is associated with higher mor-
tality (OR, 1.17; 95% CI, 1.16–1.18) than positive
BE (OR, 1.01; 95% CI, 0.99–1.02) (Fig.  4). The rela-
tionship between lactate and mortality is stronger
(OR, 1.32; 95% CI, 1.31–1.34), per unit increase, than
 Morris et al

TABLE 1.
Patient Characteristics by Lactate Measurement Status
Lactate Measurement, No Lactate Measurement,
Variables N = 63,316 N = 59,936 p

Age (yr), median (IQR) 1.59 (0.28–6.94) 1.43 (0.29–5.84) < 0.001
Planned admission after surgery, n (%) 23,679 (37.4) 16,161 (27.0) < 0.001
Invasive mechanical ventilation, n (%) 44,292 (70.0) 25,748 (43.0) < 0.001
Length of stay (d), median (IQR) 2.26 (1.01–5.33) 1.74 (0.84–4.07) < 0.001
Pediatric Index of Mortality 2 (%), median (IQR) 1.25 (0.61–3.97) 0.99 (0.27–2.23) < 0.001
Outcome, n (%)
 Alive 60,771 (96.0) 58,454 (97.5) < 0.001
 Died 2,545 (4.0) 1,482 (2.5)
IQR = interquartile range.

between absolute BE and mortality (OR, 1.13; 95% CI,
1.12–1.14).
This finding is confirmed by comparison of the
sORs for mortality for an increase of 1 sd in lactate
and BE (lactate sOR, 1.86 [1.82–1.91]; BE sOR, 1.74
[1.70–1.79]; p < 0.001).
Analysis 3 (n = 123,252)
Table  2 explores the effect of substituting absolute
BE with lactate in a PIM2 model using three dif-
ferent treatments for handling missing lactate. The
highest AUROC and lowest AIC were found if miss-
ing lactate was assigned a value of 1. This handling
of missing lactate values was therefore applied in
Analysis 4.
Analysis 4 (n = 123,252 [PIM2]; n = 30,297
[PIM3])
Addition of lactate to modified PIM2 (without BE)
resulted in a small improvement of performance over
addition of absolute BE, whereas adding both lac-
tate and BE achieved the highest AUROC of 0.8729
(Table 3). Similar effects were seen when the analysis
was repeated on a modified PIM3 score for the 2015
cohort of patients (Table 3).
Exploration of Adding in Venous BE Values
(n = 41,676)
We repeated the modeling undertaken in Analysis
4 on a subset of patients from the ANZPIC registry
(n = 41,676), with an additional step of allowing venous

Figure 2. Relationship between lactate and actual base excess (A) and absolute base excess (B).

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 Online Clinical Investigations

and 28.9% (5,798/20,055) of admissions with both lac-

tate and BE values, respectively.
The analysis demonstrated that performance of
PIM2 was slightly improved if venous BE values were
allowed in addition to arterial and capillary values
(AUROC 0.9098 vs 0.9086) (Supplementary Table,
http://links.lww.com/PCC/B970).

Figure 3. Relationship between lactate and mortality.
as well as arterial and capillary BE samples. Missing BE
was set at zero, as per established PIM guidance, and
missing lactate set to 1, as per the findings in analysis
3. We excluded the subset of patients from PICANet as
guidance to date has been to not enter a value for BE for
venous samples. As a result, only 3.0% (2,441/81,576) of
PICANet BE values were documented as being venous,
compared with 15.0% (6,253/41,676) of ANZPIC reg-
istry BE values, corresponding to 5.6% (2,302/40,821)
DISCUSSION
In this retrospective study of a large international
dataset, PICU admission lactate level was found to
be more strongly associated with mortality than BE.
Exploratory analysis of this dataset suggests that in-
corporation of lactate into the PIM model results in a
small improvement in model performance.
A major strength of the study is the large sample of
patients from the UK and ROI and ANZ, with excel-
lent systems of audit in place that capture information
on every child admitted to a PICU in these countries
(PICANet and ANZPIC). This allowed a comprehen-
sive evaluation of the research question.
Despite the work of Weil et al (22) as early as the
1970s demonstrating the importance of blood lactate
as a marker of the severity of shock and critical illness
(20, 21), widespread measurement of lactate was in-
frequently undertaken in ICU until comparatively re-
cently. Evaluation of lactate was not incorporated into
the work to develop PIM, undertaken in the early 1990s,

Figure 4. Relationship between mortality and actual base excess (A) and absolute base excess (B).

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 Morris et al
TABLE 2.
Effect of Substituting Lactate for Absolute Base Excess in Pediatric Index of Mortality 2
Using Three Different Treatments for Missing Lactate
Models
Model 1: original PIM2 model
Model 2: substitute lactate for BE in PIM2
Set missing lactate to 0
Model 3: substitute lactate for BE in PIM2
Set missing to 1
Model 4: Substitute lactate for BE in PIM2
Set missing lactate to 1, replace values between
0 and < 1 with 1, put the term (lactate–1) in the model
BE = base excess, PIM = Pediatric Index of Mortality.
to develop PRISM, undertaken in the mid-1980s, or in-
cluded in the development of the most widely used se-
verity of illness measure in adult intensive care (Acute
Physiology and Chronic Health Evaluation) (1, 2, 22).
Findings of single-center studies have suggested
that lactate adds prognostic value to existing scoring
systems and should be considered for inclusion into
PIM and PRISM (6, 16, 23). These studies add to a
large body of evidence supporting a consistent asso-
ciation between blood lactate and mortality in crit-
ically ill patients across neonatal, pediatric and adult
critical care populations (5–10). For example, in
the Australasian Resuscitation In Sepsis Evaluation
(ARISE) study of adults with sepsis those randomized
to goal-directed therapy because of isolated hyperlac-
tatemia had 1.7 times the risk of 90-day mortality com-
pared with patients with isolated hypotension (10).
Blood lactate has recently been incorporated into new
prognostic models that have been developed for severe
pediatric sepsis (18) and mortality prediction in sick
African children (19).
Although the normal lactate concentration in un-
stressed individuals is 1.0 ± 0.5 mmol/L (20), patients
with critical illness are generally considered to have
normal lactate levels at concentrations of less than 2
mmol/L. Nichol et al (25) evaluated the relationship
between lactate and hospital mortality in a cohort of
7,155 consecutive admissions to ICU and confirmed
a relationship between both admission lactate (OR,
2.1 [1.3–3.5]) and time-weighted lactate concentra-
tion (OR, 3.7 [1.9–7.0]) and hospital mortality (24).
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Area Under the
Receiver Operating
Characteristic Curve 95% CI AIC
0.8682 0.8628–0.8737 25424.649
0.8699 0.8645–0.8753 25401.247
0.8712 0.8659–0.8765 25348.149
0.8710 0.8657–0.8764 25355.850
This significant association was first detectable at lac-
tate concentrations greater than 0.75 mmol/L, lead-
ing the authors to suggest that the current reference
range for lactate in the critically ill may need to be
reassessed.
A significant limitation of this study is the number
of cases without a lactate and/or BE measurement.
During the first year of the study (2012), a higher pro-
portion of cases had a BE available compared with
lactate (62.5% vs 46.6%), whereas by 2015, the pro-
portions were similar (61.3% vs 60.7%) in keeping
with widespread incorporation of lactate sensors into
ICU point of care blood gas analysers. Overall how-
ever ~50% of cases did not have a measurement or BE
or lactate, most likely because these patients did not
have a blood sample taken for blood gas analysis in the
first hour of ICU admission. However, the handling of
missing data is something that is considered in the de-
velopment of any prediction model, and the original
PIM model, and subsequent revisions (PIM2, PIM3),
was validated in the setting of comparable levels of
missing values of Po2 and BE on blood gas analysis.
Another relative limitation of our study is that we had
complete PIM3 data only for 2015, although this co-
hort still amounted to over 30,000 admissions, so had
to undertake most of the analysis using PIM2. In addi-
tion, we were only able to explore the relationship be-
tween BE, lactate, and mortality, as these are recorded
routinely, and did not have data to include or explore
other variables such as pH, Hco3, anion gap, albumin,
or strong-ion gap.
 Online Clinical Investigations

TABLE 3.
Modeling the Effect of Adding in Absolute Base Excess, Lactate, or Both, to a Modified
Pediatric Index of Mortality 2 and Pediatric Index of Mortality 3 (without Base Excess)
Area Under the
Likelihood Receiver Operating
Model Ratio Test p Characteristic Curve 95% CI

Modified PIM2 (without BE) Add absolute BE 432.41 < 0.0001 0.8682 0.8628–0.8737
n = 123,252 Add lactate 508.91 < 0.0001 0.8712 0.8659–0.8765
Add both absolute BE 680.89 < 0.0001 0.8729 0.8676–0.8783
and lactate
Modified PIM3 (without BE) Add absolute BE 68.28 < 0.0001 0.8670 0.8614–0.8726
n = 30,297 Add lactate 138.37 < 0.0001 0.8694 0.8639–0.8750
Add both absolute BE 155.34 < 0.0001 0.8713 0.8658–0.8768
and lactate
BE = base excess, PIM = Pediatric Index of Mortality.
Likelihood ratio test against modified PIM without BE, area under the receiver operating characteristic curve. Missing BE set to zero,
missing lactate set to 1.

A challenge with any severity of illness score is how ACKNOWLEDGMENTS

to deal with missing values, with the usual assump-
tion being that missing values are replaced with a
“normal” value for that variable. In the case of PIM2,
a value of zero would be assigned for a missing ab-
solute BE value. We know that children who have a
blood gas taken within the first hour of ICU admis-
sion are a more at-risk population with higher prob-
ability of death than children in whom a blood gas is
not undertaken. By considering venous BE values as
missing values in PIM, and thereby assigning a zero
value for BE, we have until now potentially underes-
timated the risk of death for these cases. The analysis
undertaken in a subset of over 40,000 ANZ admissions
suggests that allowing venous BE values results in a
slightly improved PIM2 performance. In this study, we
also explored the impact of adopting a value of either
0 or 1 for missing lactate and found slightly better per-
formance if missing values were set to 1.
CONCLUSIONS
In this large international, retrospective study, PICU
admission blood lactate was more strongly associated
with ICU mortality than absolute BE. Adding lactate
into the PIM model results in a small improvement in
performance. Any potential improvement in PIM per-
formance must be balanced against the added burden
of data capture when considering potential incorpora-
tion into the PIM model.
We would like to thank all participating ICUs for their
support and submission of data to Pediatric Intensive
Care Audit Network (PICANet) and the Australia and
New Zealand Pediatric Intensive Care Registry. The
PICANet Audit is commissioned by the Healthcare
Quality Improvement Partnership as part of the National
Clinical Audit Program. The PICANet Audit is funded
by NHS England, NHS Wales, NHS Lothian/National
Service Division NHS Scotland, the Royal Belfast Hospital
for Sick Children, The National Office of Clinical Audit,
Republic of Ireland, and HCA Healthcare.
1 Paediatric Intensive Care Unit, Birmingham Children’s
Hospital, Birmingham, United Kingdom.
2 Institute of Applied Health Research, University of
Birmingham, Birmingham, United Kingdom.
3 Division of Epidemiology and Biostatistics, School of
Medicine, University of Leeds, Leeds, United Kingdom..
4 Paediatric Intensive Care Unit, Children’s Hospital at
Westmead, Sydney, NSW, Australia.
5 Paediatric Intensive Care Unit, Queensland Children’s
Hospital, Brisbane, QLD, Australia.
Supplemental digital content is available for this article. Direct
URL citations appear in the printed text and are provided in the
HTML and PDF versions of this article on the journal’s website
(http://journals.lww.com/pccmjournal).
Dr. Parslow's institution received funding from the Healthcare
Quality Improvement Partnership. The remaining authors have
disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: Kevin.morris3@nhs.net

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 Morris et al
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