Seminars in Pediatric Surgery 24 (2015) 3236

Contents lists available at ScienceDirect

Seminars in Pediatric Surgery

journal homepage: www.elsevier.com/locate/sempedsurg

Innovations and controversies in the monitoring of pediatric patients

in the ICU
David Bliss, MDa,b,n
a
b

USC, Keck School of Medicine, Los Angeles, California

Surgical Critical Care, Children's Hospital Los Angeles, Los Angeles, California

a r t i c l e in f o

Keywords:
System of systems
Monitoring
Pediatric intensive care
Pediatric delirium
Biomarkers

abstract
In recent years, the number of monitoring options for ICU clinicians has continued to proliferate, but
there has been limited information regarding their value in shortening length of stay, averting
complications including death, or improving functional outcomes. However, innovative new approaches
hold the promise of integrating data sets to help clinicians avert complications and to detect evolving
organ dysfunction earlier.
& 2014 Elsevier Inc. All rights reserved.

Background
The simultaneous development of discrete spaces and stafng
as well as devices to support and monitor critically ill patients in
real time has fostered the proliferation of intensive care units
(ICUs). In turn, the ICU environment has permitted clinicians to
support increasingly complex and profoundly ill patients with
improvements in both quality and durability of outcomes. Core
components of ICU care include the application and interpretation
of monitoring devices to detect important physiologic changes,
mitigate or deter harm, and track the effectiveness of interventions. Whether it is standard equipment such as non-invasive
blood pressure or sophisticated invasive devices such as pulmonary artery catheters, each requires an understanding of data
accuracy, device safety and reliability, and operational effectiveness. Moreover, the quantity and complexity of data requires that
clinicians develop methods to lter noise and to integrate the
useful information. This review examines new meta-systems to
automate the interpretation and integration of clinical data as well
as novel and potentially controversial approaches to improve
patient outcomes.

System of systems
Traditional monitoring methods attempt to isolate specic physiologic or anatomic variables in order to interrogate single-system
performance. For example, while continuous electrocardiography
n
Correspondence to: Department of Surgery, Children's Hospital Los Angeles,
4650 Sunset Blvd, Mailstop #72, Los Angeles, CA.
E-mail address: dbliss@chla.usc.edu

http://dx.doi.org/10.1053/j.sempedsurg.2014.11.007
1055-8586/& 2014 Elsevier Inc. All rights reserved.

is considered standard of care in an ICU environment, it can only

report cardiac rate and rhythm and cannot relay information about
pump effectiveness. The clinician must synthesize a variety of data
to construct a patient-specic appraisal of real-time physiologic
performance and treatment response. Furthermore, the predicate
assumption is that the clinician will review and successfully
integrate the data in a timely manner. Though patient information
is gathered throughout the day, it is rarely directed to the supervising clinician except when critical values emerge or the clinician
interrogates the patient's status. Recognition of patterns of disease
or therapeutic response may involve gathering data that is
temporospatially discordant. For example, a mechanically ventilated child at risk for ventilator-associated pneumonia (VAP) might
manifest increasing oxygen requirements in the early morning
hours, a rising white blood cell count the prior evening, and chest
radiographic ndings the following afternoon. While the astute
clinician will almost certainly intervene appropriately once a
preponderance of such data has manifested, care is reactive rather
than preventative.
In addition, clinicians are subject to errors from data fatigue
and cognitive errors. In the face of exploding data sets, caregivers
frequently employ logic shortcuts (heuristics) to lter information
and to make decisions under increasing time constraints. Not
surprisingly, clinicians may be wholly unaware of relevant information, may fail to recognize a pattern of risk emerging from
disparate sources of data, and must, therefore, rely upon the oftrevered clinical judgment to make care decisions. In his book,
Thinking Fast and Slow, Nobel Prize winner Daniel Kahneman1
describes decades of human behavioral science that illustrates the
myriad pitfalls of the judgment approach. Irrespective of education, intelligence, or experience, humans routinely employ a
variety of heuristics. Indeed, Dr. Kahneman's research demonstrates

D. Bliss / Seminars in Pediatric Surgery 24 (2015) 3236

that education and intelligence may not only fail to confer

protection from such errors but may predispose to greater condence in the error. While a detailed description of his highly
relevant ndings is beyond the scope of this article, there are
several that inform the nature of data use and interpretation in the
ICU. Kahneman describes a concept of WYSIATIwhat you see is
all there is. In repeated studies of human behavior, it is clear that
individuals will make crucial judgments based upon available
information whether or not the data provided is adequate. This
reductive approach allows clinicians to make a new situation
appear to mirror a prior experience and, therefore, to treat it
similarly. Not surprisingly, the outcomes may differ substantially,
but the clinicians fail to understand why. Kahneman and Tversky's
Nobel Prize winning Prospect Theory clearly dispels the closely
held myth that humans are inherently good statisticians or able to
rationally and completely evaluate data. Unfortunately, ICU clinicians are no less subject to these limitations. Experience and
knowledge may not be adequate prophylaxis against such errors
of omission or commission.
Engineers have long understood that complex interacting
systems cannot be viewed solely by interrogating component
sub-systems in isolation. Indeed, intricate algorithms are important to simultaneously observe whole system and component
health and function. Just as adequate energy production by a
generator does not guarantee optimal function of all connected
devices, individual organ or tissue perfusion cannot be determined
by the measurement of cardiac output alone. Moreover, salutary
effects on one system may have untoward results in others. For
example, while increasing positive end-expiratory pressure may
improve oxygenation as determined by blood-gas analysis or pulse
oximetry, under some conditions the increased pulmonary and
intrathoracic pressures may contribute to ventilator-induced lung
injury (VILI), diminish venous return and cardiac output, and
potentially harm cerebral, hepatic, and renal venous drainage.
Without tools to simultaneously interrogate these matters or to
estimate risk and reward, clinicians must use either experience or
iterative processes to evaluate impacts of ICU treatments.
Peter Pronovost, MD, Professor of Anesthesia and Critical Care
at the Johns Hopkins School of Medicine and winner of a
MacArthur award in 2008, has proposed just such an Engineering
approach to ICU care. Dr. Pronovost rst demonstrated that
optimization of standards for central venous catheter insertion,
comprised of elements culled from the best available data, could
signicantly decrease central line-associated blood stream infection (CLABSI).2 The Hopkins group has since moved deeper into
the safety arena with a system-of-systems approach, whereby a
supervisory device automatically takes data from multiple, disparate sources and reports patient risk proles in real time. After
examining existing data to determine the risk factors for highvalue target problems such as myocardial infarction (MI),
ventilator-induced lung injury (VILI), iatrogenic infection, venous
thromboembolism (VTE), and others, Dr. Pronovost's team reached
two critical conclusions: (1) many monitors and devices use
proprietary communication protocols that are incompatible with
one another and (2) increasing number of clinician checklists and
analog data recording of digital outputs simply increased workload
without improving outcomes.3 Dr. Pronovost's team convinced key
device manufacturers to collaborate on communication systems to
allow the development of a supervisory analytical tool to report
risk in real time. Now in active use in the adult ICUs at Johns
Hopkins, the system provides anticipatory reporting of risk for
these disorders and facilitates Nursing and Physician intervention
in advance of complications while decreasing unproductive,
analog data logging by clinicians. Specically, the system employs
risk stratication algorithms that integrate data from multiple
sources to notify clinicians whether a patient is in one of three

33

categorieslow, moderate, or high risk of a particular complication. For example, if a patient at risk for VAP has not had
appropriately-timed oral care or positioning or has developed
physiologic indicators of concern, the system provides visual cues
to the bedside nurse to drive further evaluation.
Several potentially high-value changes may emerge from this
approach. First, the integrative and real-time nature of these
systems actively interrogates relevant data sets and reports risk.
Second, it takes advantage of digital inputs to bypass human error
in recognition and recording to maintain data integrity. Third, it
allows bedside personnel to eliminate transcriptional tasks that
detract from patient care, decrease caregiver satisfaction and
burnout, cause cognitive fatigue, and clutter medical record
systems. Finally, by identifying risk proles, the system-ofsystems approach augments clinical judgment to recognize and
avert negative events. Though these systems are in early trials,
preliminary experience suggests that they may decrease diagnostic
delays and inaccuracy while saving healthcare dollars and improving clinician satisfaction.3
The implications for care of Pediatric patients are potentially
profound. While the risk proles and most common complications
may differ substantially from adults, the principles remain that
automated integration of information may achieve similar
improvements in the care of ill children. Clinicians will need to
dene Pediatric-specic categories, the potential predictive data
elements, and weighting algorithms to integrate the information
and stratify risk prospectively. For example, patients at risk for the
development of severe sepsis may undergo regular interrogation
of temperature, heart rate, blood pressure, end-tidal CO2, pulse
oximetry, urine output, laboratory tests such as white blood cell
count, lactate levels, uid cultures, radiology results, and others to
report low, medium, or high risk and to call attention to remediable matters. Similarly, ventilator settings, airway pressures and
resistance, end-tidal CO2 and oxygenation, labs, and x-rays could
predict and help avert the risk of VILI or pneumonia. Rather than
focus excess attention upon interpreting individual data elements
or completing checklists, clinicians could focus on early risk
reduction, avoidance of complications, or early intervention.
In this unied eld theory of critical care, clinicians may
simultaneously view the larger picture of integrated system
function (the whole patient) while validating single-system
impacts or function through narrow data sets. Clinicians who
acquired skills prior to the development of many modern monitors
often decry the modern providers seeming fascination with the
plethora of tools to interrogate and monitor patients as missing
the art of evaluating the patient as a unitary organism. In many
respects, the system-of-systems approach recapitulates but
updates this approach by folding the best of knowledge and
experience (data) into algorithms that can give the information
context (integration) and foster early action by the clinician to
avert complications (intervention). While some may fear that
these systems will be used to replace clinician judgment, others
will see them as powerful tools to supplement medical knowledge
and decision making in the interest of optimizing patient care.
Indeed, as Medicine has turned to the Aerospace industry to learn
how to achieve a near-zero error rate and improve outcomes,
predictive analytics have emerged as crucial tools. With explosive
developments in computing technology and algorithms that can
learn. medicine in general and critical care in specic are poised
to take a leap forward through a system-of-systems approach.

Controversial and novel monitoring

Notwithstanding the ongoing development of supervisory systems discussed above, conventional concepts of individual-system

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D. Bliss / Seminars in Pediatric Surgery 24 (2015) 3236

monitoring remain the order of the day in most ICUs. The vast
majority of these devices are non-controversial and well understood. ECG, blood pressure, pulse oximetry, end-tidal carbon
dioxide (ETCO2), and others are relatively standard components
of the ICU lexicon and provide useful data about cardiopulmonary
performance. While opportunities exist to make better use of some
of these devices such as waveform interpretation in ETCO2 or use
of co-oximetry to monitor total circulating hemoglobin (Hb) and
its subsets (Met-Hb, Carboxy-Hb), these have not yet been widely
adopted. ETCO2, for example, is sensitive to changes in cardiac
performance, metabolic rate, airway resistance, ventilator mode,
rate, and pressure, and patient effort. With breath-to-breath
reporting, the device can indicate changes as disparate as airway
obstruction/disconnection, malignant hyperthermia, bronchospasm, or decreased cardiac output. In the non-neonatal population, continuous co-oximetry and ETCO2 allow clinicians to
eliminate a substantial amount of blood-gas analyses while still
having robust information about cardiopulmonary performance.4
In contrast, ETCO2 may have limitations in premature and very
low-birth-weight infants that preclude their use to predict absolute values but remain good trending devices.5 A comprehensive
review of the technology and its applications is available in the
Journal of Critical Care.6
Monitoring for head injury in children remains fraught with
confusion. The 2012 Guidelines for Pediatric Head Injury state that
intracranial pressure (ICP) monitoring for patients with Traumatic
Brain Injury (TBI) and a Glasgow Coma Score o8 is an option
with considerable variability in reported benets or harm of ICP
monitoring.79 Indeed, the use of intracranial monitoring is relegated to an option in the most recent guidelines due to the poor
quality of evidence available (level 3). Once thought to be the gold
standard for both observation and therapy in head injury, ventriculostomies may not yield improved outcomes in children. In a
randomized trial conducted in South America including children
413 years old, there appeared to be no advantage over other
monitoring methodologies and medical management.9 In a review
of ICP monitoring practices in the United States, the authors found
that infants and young children and patients treated at Pediatric
trauma centers underwent intracranial monitoring less frequently.
Notably, these approaches were volume-independent.10
Strain-gauge devices, sometimes referred to as bolts. may
provide pressure trends for 2448 h but can begin to drift and
cannot be re-calibrated. Nevertheless, the pressure and waveform
may assist clinicians in tracking the efcacy of therapies including
decisions to image or intervene. Systems that detect brain oxygenation (Pb02) and metabolic byproducts have been developed to
examine regional performance. However, benchmark data are still
being developed, and it remains uncertain whether monitors
should be placed within injured brain, surrounding at-risk brain
(penumbra), or distantly. However, given that therapies to treat
global intracranial hypertension continue to have poorer outcomes
than desired, it is compelling to consider methods to examine
regional perfusion and performance. Ultimately, this may open
opportunities for clinicians to track the efcacy of therapies with
specic metrics for the injured or imperiled brain.
Monitoring for levels of sedation, pain control, and delirium has
become increasingly relevant in the ICU. In one of the most
signicant advances in adult ICU medicine in several decades, a
consortium of ICUs has demonstrated convincing evidence that
programs to detect and avert or address delirium can decrease ICU
mortality by as much as 10%.1114 Interestingly, the majority of
delirium was found to be hypokinetic and, therefore, readily
overlooked. By applying screening tools tailored to bedside providers coupled with avoidance of sedation medications more
closely associated with delirium as well as regular holidays from
sedation, units have been able to drop rates of delirium and obtain

improved survival. Investigators have demonstrated through serial

neuropsychiatric testing and brain imaging that both functional
and structural changes persist for 612 months or more even in
young adults who experience severe sepsis.15,16
In follow-up studies, researchers instituted methods to mitigate
the harm associated with ICU delirium. Patients experiencing
delirium had a 3-fold increase in 6-month mortality when compared to those who do not.17 By employing strategies to minimize
sedation, use fewer medications associated with delirium, and
screen for hypokinetic delirium, the authors were able to decrease
the prevalence of the disorder in the ICU.18 More importantly, the
institution of protocolized daily holidays from sedation and
attempts at spontaneous breathing in ventilated patients led to
substantial improvements in 1-year mortality.18 Additional benets included shorter lengths of stay and better short-term performance on cognitive testing. Comprehensive review of the
available data has been published previously.19
Pediatric information with respect to both delirium and cognitive outcomes is sparse, at best. However, a number of related
ndings raise the specter that many standard approaches to the ill
Pediatric patient may have more lasting effects than once thought.
The Flick group at the Mayo Clinic has demonstrated from
population studies that general anesthetics may affect school
performance in matched pairs of children where one member of
the pair underwent uncomplicated, elective operation.20 Prospective studies are underway through the Smart Tots Initiative (www.
smarttots.org) to determine whether retrospectively observed
ndings are true; whether they correlate with type, number, or
duration of anesthetic; and how durable the impacts may be. In
the interim, emerging evidence that medication categories such as
benzodiazepines, barbiturates, inhalational agents, and others may
cause neural injury or death in developing primates has led many
clinicians to reconsider their use in children.20 Though the greatest
concern is for the young brain, the ndings by the adult researchers of structural and functional decits in young adult patients
after ICU illness suggest, in combination with the emerging
Pediatric data, that many of the current sedation approaches
may not be as benign as previously considered.
As a consequence, there is a three-pronged approach to
dening and addressing sedation and anesthesia issues in children. First, as described above, groups have formed to study
cognitive outcomes in children exposed to these medications.
Future work will address whether drug type, dose, combination,
duration, or other factors are involved. Second, advocates exist for
more aggressive screening and monitoring. While validated scales
exist in the adult ICU, only recently have comparable scales been
developed for children. In one recent study, a 20% prevalence of
delirium was found in the Pediatric ICU.21 However, unique
challenges exist in the Pediatric environment including the
populations of pre-verbal and developmentally delayed children.
Others have suggested using non-invasive monitoring. Continuous electroencephalography or its derivative, bispectral index
monitoring (Bis), has been suggested. However, little evidence
exists that this impacts the administration of anesthesia or
sedation in children.22 Currently, the best method appears to be
periodic interruption of medications to assess cognitive state.
Thirdly, clinicians have been searching for medication classes and
sedation protocols to mitigate the potential harm. Some have
suggested the use of non-pharmacologic methods, intermittent
sedation in lieu of continuous drips, and anti-psychotic medications such as haloperidol.19 Though no practice guidelines yet
exist for children, the principles currently in use in the Adult ICU,
including minimizing sedation and using medications with a
lower incidence of delirium, interruption of sedation, delirium
screening, and early intervention, have the potential to yield
substantial patient benet.

D. Bliss / Seminars in Pediatric Surgery 24 (2015) 3236

Cardiac performance monitoring has been a mainstay of ICU

medicine, yet it remains controversial whether the devices
employed can be relied upon to make therapeutic decisions and
whether they contribute to better outcomes. For over 3 decades,
pulmonary artery catheters were considered the best device to
interrogate cardiac performance in adults and were used selectively in children. However, data emerged that a large percentage
of ICU clinicians interpreted data incorrectly23,24 and, over time,
the devices fell out of favor in Pediatric ICU. Since that time,
clinicians have sought replacement methods to dene whether the
administration of uid, blood and blood products, vasoactive
medications, diuretics, or other therapies is indicated. Central
venous pressure and oxygenation monitoring,25 echocardiography26 (transthoracic or transesophageal), arterial waveform analysis,27 and others have been widely used and are touted by
manufacturers as accurate. However, in studies examining the
ability of these methods to predict uid responsiveness, they have
performed no better than a passive leg-raise test.28 More importantly, there is little data to demonstrate that ICU clinicians have
been able to leverage the data obtained from cardiac performance
monitoring to improve Pediatric patient outcomes. Additional
study is required to determine whether the apparent lack of
effectiveness is the result of inadequate or inaccurate data, misinterpretation of information, or that examining and intervening
upon cardiac performance in isolation may be counterbalanced by
other negative impacts of ensuing treatment such as increased
death rates and sepsis observed in patients receiving red blood cell
transfusions.
Finally, though laboratory testing is not generally considered
part of ICU monitoring, biomarker analysis may emerge as an
essential adjunct to detect early organ system injury or dysfunction. Most ICU clinicians are well aware of troponin and B-type
natriuretic peptide (BNP) as indicators of myocardial injury and
heart failure, respectively, and use them to guide therapies. Similar
tools are being developed for renal, hepatic, and cerebral injury,
with the greatest current promise being shown in acute kidney
injury (AKI), though their use in children has been more limited.
While mortality from AKI, as dened by pRIFLE criteria, is lower in
children than adults, it may be as high as 1736% and is associated
with increased overall increased length of ICU stay and duration of
mechanical ventilation.29,30 After screening over 24 candidate
compounds, researchers have focused on urinary and serum levels
of Cystatin-C, IL-18, and neutrophil gelatinase-associated lipocalin
(NGAL). With receiver-operator area under the curve values up to
0.85, these are relatively accurate, early predictors of AKI especially
when coupled to systematic clinical tools such as the Renal Angina
Index.31 Implicit in this discussion is the assumption that early
recognition can direct intervention and improve outcomes. Supportive data is emerging in the post-cardiac bypass population, but
will need to be replicated in other scenarios.31 In these studies,
researchers have been able to detect and intervene upon renal
injury far in advance of manifestations such as oliguria or rising
serum creatinine levels.
While it is beyond the scope of this review, there are a variety of
other biomarkers that may achieve clinical utility in the near future.
For example, pro-calcitonin has been touted as both an indicator or
infection and correlative with the resolution of illness. Several studies
have demonstrated the ability to curtail antibiotic duration, even in
neonates, and to be more reliable than conventional measures such
as white blood cell count or C-reactive protein.3236 Similarly,
considerable research has been devoted to assessing cerebrospinal
uid and serum markers of head injury. Neuron-specic enolase,
S100B, IL-6, and others have been used individually and collectively
to assess brain injury in children with promising results.36 This may
have utility in detecting sub-clinical injury and for understanding the
timing of injury peak and resolution in brain injury.

35

Summary
Monitoring in intensive care units that treat children is undergoing a reappraisal to determine which methods not only report
accurate data but also have positive impacts on patient outcomes.
Three parallel processes show promise to in this regardanalytical
tools to gather, integrate, and report data proles to facilitate
clinician decision making (system of systems), more effective use
of existing technologies and treatments including respiratory
monitors and sedation approaches, and novel biochemical testing
(biomarkers) to detect and treat organ injury earlier. The value of
these developments will be measured by the degree and signicance of their contribution to improved survival, decreased morbidity, and better functional outcomes of children.

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