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On-ward observations
in neonatal intensive care:Towards saer supplemental oxygen & IV therapy
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PROEFSCHRIFT
ter verkrijging van de graad van doctor
aan de Technische Universiteit Delft,
op gezag van de Rector Magnificus prof. ir. K.C.A.M. Luyben,
voorzitter van het College voor Promoties,
in het openbaar te verdedigen op maandag 24 september 2012 om 15.00 uur
door
Anne Catherine VAN DER EIJK
Ingenieur in Biomedical Engineering
geboren te Zwolle
On-ward observations
in neonatal intensive care:Towards saer supplemental oxygen & IV therapy
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Dit proefschrift is goedgekeurd door de promotoren:
Prof. dr. J. Dankelman
Prof. dr. H.J. Simonsz
Copromotor:
Dr. B.J. Smit
Samenstelling promotiecommissie:
Rector Magnificus, Technische Universiteit Delft, voorzitter
Prof. dr. J. Dankelman, Technische Universiteit Delft, promotor
Prof. dr. H.J. Simonsz, Erasmus Medisch Centrum Rotterdam, promotorDr. B.J. Smit, Erasmus Medisch Centrum Rotterdam, copromotor
Prof. dr. ir. C.A. Grimbergen, Technische Universiteit Delft
Academisch Medisch Centrum Amsterdam
Prof. dr. S. Bambang Oetomo, Technische Universiteit Eindhoven
Maxima Medisch Centrum Veldhoven
Prof. dr. F. van Bel, Universitair Medisch Centrum Utrecht
Prof. dr. ir. R.M. Verdaasdonk, VU Medisch Centrum Amsterdam
Prof. dr. ir. R.H.M. Goossens, Technische Universiteit Delft, reservelid
The research presented in this thesis was partially supported by
Philips Medical Systems, Boeblingen, Germany
ODAS foundation, Delft, The Netherlands
Lay-outLouise de Kruijf
ISBN 978-94-6191-355-5
Copyright , A.C. van der Eijk
All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means,
without the prior written permission of the author.
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Wires
You got wires, going in
You got wires, coming out of your skin
You got tears, making tracks
I got tears, that are scared of the facts
Running down corridors, through automatic doors
Got to get to you, got to see this through
I see hope is here, in a plastic box
Ive seen christmas lights, reflect in your eyes
You got wires, going in
You got wires, coming out of your skin
Theres dry blood, on your wrist
Your dry blood on my fingertip
Running down corridors, through automatic doorsGot to get to you, got to see this through
First night of your life, curled up on your own
Looking at you now, you would never know
I see it in your eyes, I see it in your eyes
Youll be alright
Artist: Athlete
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CHAPTER
General introduction
. Introduction
. Preterm infants, definitions & prevalence
. Prematurity, causes & outcome
. Prematurity & oxidative stress related
diseases
.. Bronchopulmonary dysplasia.. Inant respiratory distress syndrome
.. Patent ductus arteriosus
.. Retinopathy o prematurity
. Supplemental oxygen therapy
.. A brie overview o history o supplemental
oxygen therapy
. IV therapy
.. A brie overview o history o IV therapy
. Problem statements
.. Supplemental oxygen therapy
.. IV therapy
. Objectives
.. Part I Supplemental oxygen therapy
.. Part II IV therapy
. Thesis outline
. References
PART I SUPPLEMENTAL OXYGEN THERAPY
CHAPTER
Oxygenation in preterm inants; background,
target ranges & monitoring techniques
. Introduction
. Oxygen in the human body
.. The oxygen dissociation curve
. Monitoring of oxygenation
.. Physical assessment o the skin
.. Blood gas analysis
.. Continuous intra-arterial blood gas
monitoring
.. Transcutaneous oxygen measurement
.. Pulse oximetry
.. Near inrared spectroscopy
.. Capnography
. Reference values for blood oxygen levels
.. Reerence values or oxygen saturation
.. Reerence values or partial pressure o
oxygen
.. Target ranges & outcome
. Monitoring oxygenation in preterm infants:
future perspectives
. References
TABLE OF CONTENTS
CHAPTER
New-generation pulse oximeters in extremely
low birth weight inants: how do they perorm
in clinical practice?
. Introduction
. Methods
.. Patients
.. Study set-up.. Experimental set-up
.. Data analysis
. Results
.. SpO2 values
. Discussion
. References
CHAPTER
Manual adjustments o the inspired oxygen
raction in extremely low birth weight inants
. Introduction
. Methods
.. Patients
.. Experimental set-up
.. Data collection.. Target levels or SpO2
.. FiO2 adjustments
. Results
.. Patients
.. Manual FiO2 adjustments
.. SpO2 levels
. Discussion
. References
CHAPTER
Pulse oximetry alarm limits in extremely low birth
weight inants: when do deviations rom the
protocol occur?
. Introduction
. Methods
.. Working situation
.. Policy or pulse oximetry alarm limits
.. Data analysis
. Results
.. Occurrence o alarm limits
.. FiO2 levels
.. SpO2 levels
.. Characteristics o the alarm limit
adjustments
. Discussion
. References
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CHAPTER
Manual control o oxygenation in extremely low
birth weight inants: what is the nurses point
o view?
. Introduction
. Methods
.. The questionnaire
. Results
.. Manual control o oxygenation
.. Pulse oximetry
.. Pulse oximetry alarm limits
.. Suggestions or improvement
. Discussion
. References
CHAPTER
Defining hazards o supplemental oxygen therapy
in neonatology using the Failure Mode and Effects
Analysis (FMEA) tool
. Introduction
.. FMEA
. Methods
. Results
.. Step 1. Defining the topic
.. Step 2. Team assembly
.. Step 3. Process analysis
.. Step 4. Hazard analysis.. Step 5. Develop risk reduction methods
. Discussion
.. Lessons learnt by the FMEA-team
. References
PART II IV THERAPY
CHAPTER
Flow-rate variability in neonatal IV therapy: what
do we know about the flow?
. Introduction
. Methods
. Results
.. Factor 1: Vertical syringe or patient
displacement
.. Factor 2: Syringes
.. Factor 3: Inusion tubing
.. Factor 4: Check valves & anti-siphon valves
.. Factor 5: Inline filters
.. Factor 6: Add-on devices
.. Factor 7: Vascular access devices
. Discussion
. References
CHAPTER
Flow-rate variability in neonatal IV therapy
caused by the use o check valves
. Introduction
. Methods
.. Check valves
.. Experimental set-up
.. Study set-up
. Results
.. Experiment I: Adding syringes
.. Experiment II: Changing height
. Discussion. References
CHAPTER
General discussion
. Main conclusions
.. Supplemental oxygen therapy
.. IV therapy
. On the research approach
.. Supplemental oxygen therapy
.. IV therapy
. The need for standardization
. Future work
.. Changes in culture
.. Technical improvements
. Conclusion. References
APPENDICES
SUMMARY
SAMENVATTING
DANKWOORD
ABOUT THE AUTHOR
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General introduction
CHAPTER
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CHAPTER
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General introduction
. INTRODUCTION
Preterm infants are infants that are born before the expected date of birth. Due to their im-
maturity, they often require intensive care to survive with a good health outcome. Intensive
care is the division of medicine that is concerned with the continuous monitoring and sup-
port of vital functions of critically ill patients. To be able to meet the specific needs of preterm
infants, dedicated neonatal intensive care units (NICUs) have been established worldwide. In
these NICUs virtually all preterm infants receive supplemental oxygen therapy and intrave-
nous (IV) therapy. Both therapies, essential but potentially dangerous, will be studied in this
thesis.
Supplemental oxygen therapy reers to the therapy where a gas mixture with >21% o oxy-
gen is supplied to the patient via (mechanical) ventilation. Due to the immaturity o the pre-
term inants lungs, supplemental oxygen therapy is oten needed immediately ater birth to
reach and maintain adequate oxygenation o the preterm inant. Unortunately supplemen-
tal oxygen therapy is not without risk. Both too high and too low blood oxygen levels may
have severe consequences or the development o the preterm inant.
The immaturity o organs and/or severe illness are also reasons why IV therapy is essential
or preterm inants hospitalised on a NICU. In IV therapy various types o nutrition, drugs,
and/or fluids are administered directly into the veins o the patient via a vascular access
device. Because o the limited vascular access possibilities, multi-inusion is used. In multi-
inusion therapy, several inusions are supplied to the inant via a single catheter. To ad-
minister the IV fluids with a pre-programmed flow-rate into the patient, syringe pumps are
requently used. Although it is expected that the IV substances are supplied to the patient
with the pre-programmed flow-rate, it has been shown that the actual volume delivered
to the patient can vary over time. Especially in preterm inants, these changes in delivered
volume can have severe consequences.
In the next paragraphs the background o prematurity, supplemental oxygen therapy, and
IV therapy are discussed in more detail. In the final paragraphs o this chapter (1.7 to 1.9)
the problem statements, objectives, and thesis outline are presented.
To be able to meet the specific needs of preterm
infants, dedicated neonatal intensive care units
have been established worldwide.
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CHAPTER
.PRETERM INFANTS, DEFINITIONS & PREVALENCE
A term, healthy newborn inant is born ater a pregnancy duration o 37 to 42 weeks with
a birth weight (BW) o approximately 3.5 kg. The pregnancy duration, or gestational age
(GA), is calculated rom the first day o the last menstruation o the mother. When an in-
ant is born with a GA 37 weeks it is classified as preterm, very preterm (
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General introduction
.PREMATURITY, CAUSES & OUTCOME
Preterm inants are either born spontaneously (40 to 45%), by induced labour or by
caesarean section. The latter two are perormed because o preterm premature rupture o
membranes (25 to 30%) or because o maternal or oetal indications (30 to 35%).7The cause
or prematurity is multiactorial and includes maternal characteristics like race, age, weight,
health in general, and pregnancy history. The educational status, socio-economic status,
and marital status o the mother are also known to influence the pregnancy duration. 8-14
Women who are exposed to drugs, heavy alcohol use, or tobacco use during pregnancy are
known to be more likely to have babies with a low birth weight.15-17
Characteristics o thepregnancy, like assisted reproductive technologies and multiple gestation, are also risk ac-
tors or preterm labour: about 50 to 60% o all multiple gestation pregnancies end in pre-
term birth. While only 2 to 3% o the inants is part o a multiple gestation, they account or
15 to 20% o all preterm births.7, 18
Although the chances o survival or preterm inants have increased enormously in the last
decades, there is still a large part o the surviving inants that suffer rom disorders or dis-
abilities. The disabilities cover, amongst others, cerebral palsy, developmental delay, visual
or hearing impairment, speech and language difficulties, and chronic lung disease. 19, 20
The risk o adverse outcome is strongly related to the pregnancy duration and birth weight.
Hille et al.21showed that in the Netherlands 36% o the ELBW inants had moderate to se-
vere problems in overall outcome at the age o 19 years. However, it is difficult to interpret
these numbers because the medical care provided to newborn inants develops continuous-
ly, and long term outcome data are always behind on the current status o neonatal care.
.PREMATURITY & OXIDATIVE STRESS RELATED DISEASES
Being born is, from a physiological point of view, a very dramatic event. The intrauterine
environment (i.e. in the womb) is warm, sterile, and dark. Oxygen and nutrition are supplied
from the mother to the foetus via the umbilical cord. One of the major changes between
the intrauterine environment and the extrauterine environment (i.e. outside world) is the
difference in oxygen tension, the partial pressure of oxygen (PO2). The intrauterine PO2 is
about 3 kPa (20 to 25 mmHg), this is comparable with the atmosphere at the top of the MountEverest. Thus, foetal development takes place in a relative hypoxic environment compared to
the atmosphere at sea level where the PO2 is about 21 kPa (155 to 160 mmHg).22-24
The sudden change in oxygen tension ater birth results in a sharp increase in reactive oxy-
gen species (ROS). ROS are chemically reactive molecules that contain oxygen. At low levels,
ROS contribute to homeostasis and cell signalling processes. At higher levels, ROS can lead
to oxidative stress in the cell. Oxidative stress is defined as the imbalance between oxidants
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CHAPTER
and antioxidants. Although oxidants and antioxidants both are necessary or maintaining
lie, an imbalance in avour o the oxidants may result in cell damage or even cell death. The
imbalance can occur due to an increase in oxidant production and/or an inadequate anti-
oxidant production. To prevent oxidative stress ater birth, several processes take place in
the oetus in the final weeks beore term birth. These processes comprise, amongst others,
an increase in both antioxidants and lung suractant. Suractant is a fluid that lowers the
surace tension o the lungs, making it easier to inflate them. 23, 25
Preterm inants lack the preparation or the sudden increase in oxygen tension because
they are born too early. Consequently, their deence system or antioxidants is immature,and thereore, they are at increased risk or oxidative stress ater birth. The risk or oxida-
tive stress increases even more when preterm inants receive supplemental oxygen therapy
and/or develop inections.26-28
In 1988 Saugstad was the first to mention the term oxygen radical disease o the newborn.29
He stated that several diseases in preterm inants have a common pathogenesis via oxi-
dative stress. Since then, it became clear that diseases typical or neonatal intensive care like
bronchopulmonary dysplasia, inant respiratory distress syndrome, necrotizing enterocoli-
tis, retinopathy o prematurity, patent ductus arteriosus and periventricular leukomalacia
are associated with oxidative stress. However, it is not always clear whether the presence o
oxidative stress is a cause or a result o the disease process.26, 29-31To show examples o the
possible consequences o suboptimal or incorrect use o supplemental oxygen therapy, our
o the disorders mentioned above are discussed in more detail in the next paragraphs.
..BRONCHOPULMONARY DYSPLASIA
Bronchopulmonary dysplasia (BPD) is a disorder characterised by respiratory distress and
airway inflammation.32The disorder was first described in 1967 by Northway et al.,33 and
diagnosed when there was a need or supplemental oxygen therapy at a postnatal age o
28 days. Because since then the GA o surviving preterm inants decreased, the definition
is not valid anymore. Thereore, the term new-BPD was introduced. New-BPD is diag-
nosed when there is need or supplemental oxygen therapy or ventilatory support at a post-
menstrual age o 36 weeks, regardless o the GA or postnatal age.
Studies on the prevalence o BPD ound the disorder in 22% o all inants with a birth weight
between 501 and 1500 grams.34, 35The exact pathogenesis o BPD is unclear, but it seems to bemultiactorial. Risk actors are, amongst others, low birth weight, mechanical ventilation,
and supplemental oxygen therapy. To treat the symptoms o BPD several types o medi-
cation, like corticosteroids, are available. In some cases special mechanical ventilation is
needed to prevent urther lung damage.36-39
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General introduction
..INFANT RESPIRATORY DISTRESS SYNDROME
In order to breathe normally, the alveoli in the lungs need to be inflated. To inflate the
alveoli, suractant is required. Due to the short pregnancy duration, in very preterm in-
ants, there is oten a suractant deficiency. As a result o this lack o suractant, the alveoli
collapse and the total lung capacity decreases. This phenomenon is reerred to as (Inant)
respiratory distress syndrome ((I)RDS). Symptoms include laboured and ast breathing,
cyanosis, grunting, and nasal flaring.
To diagnose IRDS, radiography is used: a low lung volume is one o the signs or IRDS.
Due to the decreased lung capacity, mechanical ventilation and supplemental oxygentherapy are required. The incidence o IRDS is inversely related to the pregnancy duration.
Thanks to the use o both antenatal steroids to promote lung maturation and the use o
suractant therapy ater birth, the incidence o IRDS in preterm inants has been reduced
enormously.36, 40
..PATENT DUCTUS ARTERIOSUS
The blood circulation o a oetus includes a connection between the main pulmonary
artery and the aorta. This connection, the ductus arteriosus, allows the blood to bypass
the not yet ventilated lungs. Ater birth, several physiological changes cause the closure o
the ductus arteriosus to make sure that oxygen-poor blood starts to enter the lungs. When
the ductus arteriosus does not close (completely) within 24 to 72 hours ater birth, a patent
ductus arteriosus (PDA) is diagnosed.41
About 65% o the inants born with a GA
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CHAPTER
.SUPPLEMENTAL OXYGEN THERAPY
Ater the outline about the diseases that are caused or ollowed by suboptimal oxygenation
it is obvious why maintaining adequate oxygenation in preterm inants is a major issue. In
healthy adults and children adequate oxygenation is maintained by a network o complex
processes with multiple parameters influencing each other. To reach and maintain adequate
oxygenation in preterm inants, it would be desirable or neonatologists to be able to moni-
tor and control these parameters (continuously). Although current mechanical ventilators
and monitoring techniques are sophisticated, it is still difficult to monitor and control therelevant parameters in preterm inants.
One o the parameters that can be monitored is the arterial oxygen saturation (SaO2). In
preterm inants the SaO2 is determined intermittently by blood gas analysis, and conti-
nuously with a non-invasive sensor, the pulse oximeter. The SaO2 determined by pulse
oximetry is reerred to as SpO2. When the SpO2 level is outside the desired range an alarm
sounds. To recover the SpO2 level NICU staff can, amongst others, adjust the raction o
inspired oxygen (FiO2) in the gas mixture supplied to the inant. The FiO2 can be adjusted
rom 21% (room air) to 100% (pure oxygen).
Currently, in neonatal intensive care the FiO2 level is adjusted manually, mainly by the
nursing staff. A simplified block scheme o this process is shown in Figure 1.2. Although
supplemental oxygen therapy increased chances o survival ater preterm birth, it has been
known or about 60 years that supplemental oxygen therapy in preterm inants is not with-
out risks.75-77
FIGURE .The process o controlling oxygenation. The input o the system is the target level o oxygen
saturation (SaO2) at the let side o the figure. The desired SaO2 level is compared with the SaO2 level
measured by a sensor (e.g., by a pulse oximeter). When the difference between the desired SaO2 level
and the measured SaO2 level is too large, an alarm sounds. The human controller can decide to take
action, or instance adjusting the raction o inspired oxygen (FiO2). The FiO2 is supplied to the patient
by a ventilator used or respiration. In the blood o the patient, the SaO2 level changes due to the change
in FiO2. The sensor measures a new SaO2 level which is again compared with the desired SaO2 level.
-
Targetlevel
SaO2
SaO2level in
blood
Human
controller Patient
Sensor
Alarm
+
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..A BRIEF OVERVIEW OF HISTORY OF SUPPLEMENTAL OXYGEN THERAPY
Soon ater the discovery o oxygen in 1774, this lie-giving gas was used or medical pur-
poses. In 1780 the Frenchman Chaussier was the first who used oxygen or newborn inants
with respiratory problems. From then it took one and a hal century beore oxygen was
widely and liberally used or respiratory support in newborn inants in the 1940s.76-78The
negative effects o the use o oxygen became clear several years later. In 1951, Dr. Camp-
bell was the first who assumed there was a relation between supplemental oxygen therapy
and retrolental fibroplasia, the blindness disorder now better known as ROP (see 1.4.4).79
Several other studies confirmed her hypothesis.80, 81
In 1954 a large trial was perormed to investigate the risks o supplemental oxygen therapy.
The conclusion o this trial was that it was sae to give oxygen to newborn inants as long
as the FiO2 was below 40%.82, 83Although some serious methodological errors were made
in this trial, the results were widely accepted. It was so strongly believed that FiO2 >40%
was harmul that, when an inant developed ROP, the hospital was accused or malpractice.
Ater all, the ROP was the proo that FiO2 had exceeded the 40%.75, 84
In the years after the large trial the incidence of ROP reduced dramatically. However, the
incidence of cerebral palsy and mortality increased.85, 86As a result of this change in preva-
lence of both mortality and morbidity and the fact that it became possible to monitor blood
oxygen levels, clinicians recognised more and more that they should not restrict the supply
of FiO2, but that they should restrict the actual blood oxygen levels of the preterm infant
itself. This understanding led to a more accurate control of blood oxygen levels and a more
tailored approach to the use of supplemental oxygen therapy in the NICU.87-89
.IV THERAPY
In IV therapy, various types o parenteral nutrition, drugs, and/or fluids are administered
directly into the veins o the patient. To deliver these IV substances with a pre-programmed
flow-rate to the patient, a mechanical pump pushes the plunger o a syringe with a pre-
programmed velocity into the syringe. The IV substance in the syringe flows into the
patient via flexible tubing and a vascular access device.
Oten, because intravenous access in preterm inants is limited and several IV substancesneed to be administered simultaneously, multi-inusion is used. In multi-inusion, several
syringe pumps are connected via tubing to a single vascular access device. These connec-
tions are conducted with add-on devices. A schematic overview o a multi-inusion set up
is shown in Figure 1.3. Although multi-inusion creates the possibility to provide various
substances simultaneously, the accuracy and the predictability o the volumes delivered to
the patient is limited.
General introduction
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CHAPTER
FIGURE .Schematic overview o multi inusion intravenous (IV) therapy. Two or more syringe pumps
are connected to one vascular access device via inusion tubing and an add-on device (e.g., a stopcock
with 3-way valves).
..A BRIEF OVERVIEW OF HISTORY OF IV THERAPY
The first attempts o IV therapy were already made in the Middle Ages. In 1492 the ill Pope
Innocent VIII was transused with blood rom three boys via vein-to-vein anastomosis. Re-
grettably the pope and donors died. From then until the second hal o the 17 thcentury the
knowledge o blood, the blood circulation, and IV therapy increased enormously. This in-
crease in knowledge was realised by perorming numerous experiments with blood transu-
sions in and between animals and humans. However, because these experiments requently
resulted in the death o the subjects, several governments and churches decreed the peror-
mance o blood transusions as a criminal act.90, 91
In the 1800s, the work o Dr. William Brooke OShaughnessy and his student Thomas Latta
ormed the basis or modern IV therapy. During the cholera epidemic in England in the
1830s, OShaughnessy realised that the typical thick black blood o the cholera victims was
a result o a shortage o water, saline, and alkali. Thereore, he indicated that the patients
needed injections o water and salts in the bloodstream. In 1832, Thomas Latta applied the
recommendations, and saved 8 o the 25 victims he treated with intravenous saline using a
small silver tube attached to a syringe.90, 92
Infusion tubing
Vascularacces device
To patient
Syringe pumps withsyringes
Stopcock with
3-way valves
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General introduction
Ater the results o OShaughnessy and Latta, it lasted until the two World Wars beore
urther innovations in IV therapy were made. In 1933 IV solutions came on the market in a
vacuum bottle, which eliminated microbial growth and pyrogens. In 1940, the Massachu-
setts General Hospital started the first IV team. This idea o organizing special IV teams
became very popular during the 1970s. Since then great advances in IV therapy were made.
These advances were, amongst others, the result o the development o plastic IV materials.
Today, virtually all hospitalised patients receive IV therapy.90, 91
In newborn inants IV therapy is more complicated than in adults due to, amongst others,
the small size o the vessels. Fortunately, together with the progress in the development omaterials or IV therapy in adults, the manuacturing o dedicated materials or (preterm)
newborn inants advanced as well. For example, today it is possible to buy vascular access
devices with an outer diameter o only 0.35 mm to serve the needs or ELBW inants. How-
ever, despite the presence o dedicated materials or the smallest patients, the accuracy o
the actual delivered IV substances still needs to be improved. 93-101
.PROBLEM STATEMENTS
Both supplemental oxygen therapy and IV therapy are necessary, but potentially dangerous
therapies. In the next paragraphs, the problem statements or both therapies are discussed
separately.
..SUPPLEMENTAL OXYGEN THERAPY
In supplemental oxygen therapy the FiO2 can be adjusted rom 21% (room air) to 100%
(pure oxygen) manually. Manual control o the oxygenation as described in Figure 1.2 is
time consuming and very difficult to do accurately, mainly because o the requent and un-
predictable fluctuations o the SpO2.102-107When SpO2 is outside the desired range an alarm
sounds. The high rate o alarms may lead to anxiety o patients and their amily, and to a
reduced or delayed reaction o the nursing staff.108Although supplemental oxygen therapy
has been widely used in newborn inants or more than 60 years, there is still no consensus
about the target ranges or blood oxygen levels, and the best methods to give (preterm)
newborn inants this treatment.75-77
To increase the quality o supplemental oxygen therapy and to reduce workload o thenursing staff, several groups worldwide have developed devices or (semi-)automatic control
o the oxygenation. Most o the devices or (semi-)automatic control o oxygenation adjust
the FiO2 supplied to the patient (semi-)automatically when SpO2 deviates rom the target.
The first devices that were developed were dedicated servo systems.109-112With the develop-
ment o computer aided control the devices became more advanced: Proportional-Integral-
Derivative control with or without adaptive models,52, 56, 103, 113-117dual control methods,118-120
state machine106, 121and uzzy logic control122have all been developed and tested.
To test the devices some groups used patient simulators, 52, 114, 119or animals,111, 117but most of
the groups tested their controller on patients.106, 109, 110, 112, 115, 116, 118, 122-125 The first studies did not
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First author
Time SpO2 is within target range
Manual control [%] Dedicated control [%](semi-)
Automatic control [%]
Beddis109, Collins110 -
Dugdale112 -
Taube113
Bhutani115
Morozoff121 -
Morozoff116 -
Sun122, 128 -
Claure105, 118
Urschitz106Open loop
Urschitz106Closed loop
Morozoff123State machine 57
Morozoff123Adaptive model
Morozoff123Closed loop, PID
Claure124
Claure125
CHAPTER
use an objective way to test the effectiveness of their automatic controller. This resulted in
no or weak conclusions.56, 111, 113, 116, 119, 121, 126-128Some more recent papers included tests that actu-
ally show significant improvement. Amongst the tests was the time spent within the target
range for SpO2 for manual, dedicated, and (semi-)automatic control (Table 1.1). Comparing
the devices with each other is hampered by the fact that the nurse:patient ratio, the subject
characteristics, the study period, and the study methods varied between studies. However,
although the results of the developed devices are promising, differences between manual and
(semi-)automatic control are major, and effects on long term outcome are still unknown. 129
TABLE .Time spent within the target range or SpO2 or periods on manual, dedicated manual, and
(semi-)automatic control.
The term manual control is used to reer to the situation in normal daily NICU care. Dedicated con-
trol is a situation where a physician or nurse stays at the bedside o the patient and is ocussing on
the control o the SpO2 only. In (semi-)automatic control a device controls SpO2 automatically, and/or
advises the NICU staff to make an adjustment in FiO2. Amongst others, the study methods and patient
characteristics differed, thus results between studies are difficult to compare.
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General introduction
To improve outcome or those situations where oxygenation is controlled manually, two
studies ocused on the development o protocols to standardise when, why, and how FiO2
should be adjusted.130, 131One o these studies actually showed a reduction in the incidence
o ROP.131However, both studies mention difficulties with implementation o the protocol
and compliance to it. Because none o the studies actually quantified the perormed manual
FiO2 adjustments, knowledge about the actual behaviour o NICU personnel with respect
to control o the oxygenation is still lacking.
..IV THERAPY
IV therapy is hampered by a number o complications and limitations. The most well-known are related to inections, and extravasation. While these complications are very
relevant, they are outside the scope o this thesis. The ocus in this thesis is on a, probably
underestimated, limitation in IV therapy: flow-rate variability. This flow-rate variability
is caused by multiple actors and complicates the accuracy and predictability o the actual
volumes delivered to the patient. Moreover, the flow-rate variability can lead to, or instance,
changes in the haemodynamics and oxygenation o newborn inants.93, 97, 99, 132, 133 Thereore, it
is important to minimise flow-rate variability in IV therapy in clinical practice.
Two o the actors that affect the flow-rate variability are backflow and siphonage. In si-
phonage, there is uncontrolled emptying or ree flow o substances rom a syringe into
the patient. Siphonage can occur when the syringe is not clamped or is poorly clamped in
the syringe pump or when there are air leaks in the IV-administration set.101, 134-136Backflow
can occur when multiple inusions are interconnected to each other (e.g., via a stopcock).
Because o differences in resistance in the IV-administration set, it is possible that fluids do
not flow rom the syringe into the patient but into another line instead. 137
To prevent backflow and/or siphonage there are various types of check valves available that
can be inserted in the IV-administration set. Paradoxically, while check valves are imple-
mented in IV-administration sets to minimise backflow and/or siphonage, it has been shown
that the presence of these valves can enhance flow-rate variability as well.101, 138Thus, to be able
to increase the accuracy and predictability of the volume delivered to the patient, the factors
influencing the flow-rate variability should be known and, where possible, controlled.
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. OBJECTIVES
The primary objective o this thesis is to determine the limitations o supplemental oxygen
therapy and IV therapy in current neonatal intensive care and to identiy areas or improve-
ment. To distinguish between supplemental oxygen therapy and IV therapy, the thesis is
divided in two parts. The secondary objectives are listed in the next two paragraphs.
..PART I SUPPLEMENTAL OXYGEN THERAPY
In Part I o the thesis, the work related to supplemental oxygen therapy in preterm inants
is discussed. The secondary objectives are:I.I To obtain background inormation regarding oxygenation o the human body, to get
an overview o literature on target ranges or blood oxygen levels in newborn inants,
and to evaluate methods or monitoring oxygenation in neonatology.
I.II To evaluate the perormance o new-generation pulse oximeters o three different
brands in ELBW inants.
I.III To quantiy manual adjustments in the FiO2 perormed by NICU personnel in ELBW
inants, in relation to SpO2 and bedside care.
I.IV To study the compliance to the protocol or pulse oximetry alarm limits in ELBW
inants in relation to FiO2, SpO2, and bedside care.
I.V To explore the decision making processes and obtain insight in the knowledge,
opinions, and attitude o the nursing staff towards supplemental oxygen therapy
in ELBW inants.
I.VI To prospectively evaluate hazards in the process o supplemental oxygen therapy
in very preterm inants hospitalised in a NICU.
.. PART II INTRAVENOUS THERAPY
In Part II o the thesis the work related to IV therapy in newborn inants is discussed. The
secondary objectives are:
II.I To study which actors are responsible or flow-rate variability in IV therapy with
syringe pumps.
II.II To evaluate the effect o three different types o check valves on flow characteristics
in a low-flow multi-inusion set.
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General introduction
. THESIS OUTLINE
To meet the objectives, five studies were perormed. These studies orm, together with the
literature reviews on the discussed subjects, the basis o this thesis.
The first part o this thesis is about supplemental oxygen therapy in preterm inants. Chap-
ter 2is the first chapter o Part I and provides a literature review to meet objective I.I. First
the background inormation regarding oxygenation o the human body and especially that
o preterm inants is described. Next, the working principles and (dis)advantages o current
developed methods or monitoring oxygenation are elaborated on. Thereater, an over-view o literature on target ranges or blood oxygen levels in (preterm) newborn inants
is provided. Finally, a uture perspective o the needs or oxygen monitoring in (preterm)
newborn inants is discussed. Chapter 3 describes a study to the perormance o new-
generation pulse oximeters in ELBW inants to meet objective I.II. In this study three di-
erent brands o pulse oximeters were compared by dual SpO2 monitoring in nine ELBW
inants. In Chapter 4and Chapter 5an observational study is discussed. During this obser-
vational study on-ward video and data recording was perormed to obtain insights in the
manual control o oxygenation in ELBW inants by healthcare proessionals. This obser-
vational study was set up to meet both objectives I.III and I.IV. Chapter 6provides the re-
sults o a survey amongst 24 NICU nurses. The questionnaire in this study was developed
to meet objective I.V. The questions assessed the knowledge, opinions, and attitude o the
nursing staff towards supplemental oxygen therapy in ELBW inants. The final chapter
o Part I is Chapter 7. In this chapter the hazards in the process o supplemental oxygen
therapy in preterm inants are evaluated prospectively to meet objective I.VI. The hazards
were analysed by a multidisciplinary team using the Failure Mode and Effects Analysis
(FMEA)-tool.
Part II o the thesis is about IV therapy in newborn inants and starts with Chapter 8where
a literature review is discussed to meet objective II.I. Chapter 9describes an in-vitro study
to the effect o three different types o check valves on the flow characteristics o a low-flow
multi-inusion set. This study was set up to meet objective II.II.
Chapter 10provides the general discussion about both supplemental oxygen therapy and
IV therapy. The main conclusions and the research approach o the work perormed in this
thesis are presented together with recommendations or uture work.
It should be noted that Chapters 3 to 9 are written as separate papers, consequently, there
is a certain amount o overlapping inormation within these chapters. Furthermore, in this
thesis the masculine orm is used or all healthcare proessionals and patients, merely to
simpliy the text. No discrimination is intended.
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112. Dugdale RE, Cameron RG, Tealman GT. Closed-loop
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121. Morozoff PE, Evans RW. Closed-loop control o
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124. Claure N, DUgard C, Bancalari E. Automated adjust-
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requent fluctuations in oxygenation: A pilot clinical
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127. Azhar N, Karim U. Automatic eedback control o
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1991. p. 1614-1615.
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o inspired oxygen in ventilated newborn inants. In:
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129. ODonnell CP. Automated adjustment o oxygen inventilated preterm inants: turn on, tune in, ROP out?
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130. Wilkinson DJ, Andersen CC. Bedside algorithms
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132. Stowe CD, Storgion SA, Lee KR, Phelps SJ. Hemody-
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133. Cunningham S, Deere S, McIntosh N. Cyclical
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134. Rooke GA, Bowdle A. Syringe pumps or
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dosage o opiate rom patient controlled analgesia
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137. Levi DS, Peterson N, Shah SD, Rakholia B, Haught A,
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antisiphon valves reduce flow irregularities during
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Part 1supplementaloxygen therapy
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Oxygenation in
preterm inants:background, targetranges & monitoringtechniquesA.C. van der Eijk, J. Dankelman, B.J. Smit
CHAPTER
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CHAPTER
It is inherent to their immaturity that preterm inants need some orm o physiological
monitoring during their stay on the neonatal intensive care unit. In current neonatal
intensive care at least the heart rate, respiration rate, skin temperature, and oxygen
saturation are monitored continuously. In the past 60 years, various methods to monitor
blood oxygen levels have been developed. In this chapter, background inormation about
the oxygenation o the human body, and especially that o preterm inants, is provided.
Subsequently, the working principles and (dis)advantages o methods that are available
or monitoring oxygenation are elaborated on. Thereater, an overview o literature on
target ranges or blood oxygen levels in (preterm) newborn inants is provided. Finally, a
uture perspective o the needs or oxygen monitoring in preterm inants is discussed.
OBJECTIVE To obtain background inormation regarding oxygenation o the human
body, to get an overview o literature on target ranges or blood oxygen levels in new-
born inants, and to evaluate methods or monitoring oxygenation in neonatology.
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Oxygenation in preterm infants
. INTRODUCTION
Approximately five to ten percent o all newborn inants need active resuscitation imme-
diately ater birth to survive.1The majority o these inants is born preterm. Due to the im-
maturity o organs like the lungs and brain o these preterm inants, respiratory support and
supplemental oxygen therapy are necessary to reach and maintain adequate oxygenation.
In supplemental oxygen therapy, a gas mixture with >21% o oxygen is supplied to the
patient via mechanical ventilation. In preterm inants this therapy is not only used imme-
diately ater birth, but also in the first weeks ater birth. Unortunately, supplementaloxygen therapy is not without risks. Both too low and too high levels o oxygen in the
tissues may have severe consequences or the development and outcome o preterm
inants.2Thereore, to prevent the negative effects o supplemental oxygen therapy, blood
oxygen levels o preterm inants need to be monitored closely during their hospitalization
on the neonatal intensive care unit (NICU).
In the last decades, several methods and sensors to monitor oxygenation in preterm inants
have been developed. Regrettably, these monitoring systems did not always serve the spe-
cific needs or the patients, the amily, and/or the healthcare proessionals in the optimal
way. The aims o this chapter are to provide background inormation about oxygenation o
the human body, to provide an overview o the techniques (that were) available or moni-
toring oxygenation in preterm inants, and to discuss target ranges or blood oxygen levels
in (preterm) newborn inants. Finally, the needs and uture perspectives or monitoring
oxygenation in (preterm) newborn inants are discussed.
To prevent the negative effects of supplemental
oxygen therapy, blood oxygen levels of
preterm infants need to be monitored closely.
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CHAPTER
.OXYGEN IN THE HUMAN BODY
Cells in the human body can only unction properly when the amount o oxygen delivered
to the cells is adequate to meet the demands o the cells. 3Because oxygen cannot be held
in stock in the cells, a constant delivery o oxygen is needed. 4In literature, the vaguely de-
fined term oxygenation is oten used as a measure or the amount o oxygen in the body.
However, an adequate oxygenation depends on the systemic oxygen transport (delivery),
the oxygen consumption (demand), and the mixed venous saturation (reserve).5The oxygen
delivery, the demand, and the reserve depend on, and are maintained by, multiple para-
meters. Thus, when examining whether the oxygenation is adequate or not, interpretationo multiple parameters is required.
In humans, the inhaled oxygen diffuses in the lungs rom the alveoli to the pulmonary capil-
lary blood (Figure 2.1). Most o the diffused oxygen is bound to haemoglobin, an intracel-
lular protein, within the erythrocytes (i.e. red blood cells). A small proportion o oxygen is
dissolved in blood plasma. The sum o the amount o oxygen bound to haemoglobin and
the oxygen dissolved in the plasma is the oxygen content o blood (O2ct) (equation I).6
O2ct = (k1 Hb SO2) + (k2 PO2)
Where
Hb = haemoglobin concentration (grams litre1)
SO2 = oxygen saturation o the blood (see 2.2.1)
PO2 = partial pressure o oxygen (see 2.2.1)
k1 = Hners constant (in theory, each gram o Hb binds 1.39 ml o oxygen,
in practice it is less)
k2 = solubility coefficient o oxygen at body temperature (0.23 ml litre-1 kPa-1)
The oxygen rich erythrocytes are transported through the body via blood vessels to the
tissues. The oxygen delivery (DO2) is the amount o oxygen transported rom the lungs to
the peripheral tissues, and depends on the oxygen content o arterial blood (aO2ct) and the
cardiac output (Q) (equation II en III)
DO2 = Q aO2ct
Q = heart rate stroke volume
At the places were oxygen is demanded, the oxygen dissociates rom haemoglobin and di-
uses into the cells. Ater oxygen is released, the oxygen-poor erythrocytes are transported
via blood vessels back to the heart and lungs. The difference in aO2ct and the oxygen con-
tent o the venous blood (vO2ct) is the amount o oxygen delivered to the tissues. The total
oxygen consumption (VO2) depends on Q and the amount o oxygen delivered to the tis-
sues (see the Fick equation, IV).
VO2 = Q (aO2ct - vO2ct)
(I)
(II)
(III)
(IV)
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Oxygenation in preterm infants
FIGURE . A schematic illustration o the lungs, the alveoli, and the diffusion o O2 and CO2
between the lungs and the blood. Figure adapted rom [.
..THE OXYGEN DISSOCIATION CURVE
As mentioned in the previous paragraph, oxygen binds to haemoglobin in the erythrocytes.
The percentage o haemoglobin bound to oxygen divided by the sum o all the available
haemoglobin is defined as oxygen saturation (SO2, equation V). For SO2 in the arterial
blood the abbreviation SaO2 is used. The actual amount o oxygen bound to haemoglobin
depends on the ability o haemoglobin to bind or release oxygen, i.e. the oxygen affinity.3
SO2 = [HbO2] / ([HbO2] + [Hb])
Where
[Hb] = concentration o deoxyhemoglobin in blood (can bind to oxygen)
[HbO2] = concentration oxyhemoglobin o blood (bound to oxygen)
The oxygen affinity can be described by an S-shaped graph, the Oxygen Dissociation-curve
(OD-curve, Figure 2.2). The OD-curve represents the relation between the SO2 and the par-
tial pressure o oxygen in the blood (PO2). The PO2, or the oxygen tension is the amount
o oxygen that has diffused across the alveolar capillary membrane and is dissolved in the
plasma o the blood. The PO2 is an important actor in the exchange o O2 and carbon di-
oxide (CO2) rom the blood to the tissues and vice versa. In the lungs, high levels o oxygen
tension in arterial blood (PaO2) encourage oxygen to bind to haemoglobin. 8, 9 As can be
seen in the OD-curve, at low PO2 levels the curve is steep. At these lower levels oxygen is
encouraged to peruse into the tissues.
(V)
CO2
Trachea
Alveoli
Alveoliairspace
Capillary
Redblood cell
Left Lung
O2
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CHAPTER
The relative position o the OD-curve on the x-axis equals the oxygen affinity, and is in-
fluenced by several actors, amongst others the pH, CO2, 2,3-diphosphoglycerate (2,3-DPG),
temperature and type o haemoglobin. A change in the oxygen affinity influences both the
amount o oxygen that binds to the haemoglobin when passing the alveoli, and the amount
o oxygen that is released in the tissues. It has been shown that the OD-curve can shit very
quickly in preterm inants.10,11
FIGURE .A schematic illustration of the Oxygen Dissociation-curve (OD-curve). The OD-curve links
the oxygen saturation (SO2) to the partial pressure of oxygen in the blood (PO2). The relative position
of the curve on the x-axis equals the oxygen affinity, and is influenced by several factors. Graph is based
on [].
Approximately 80% o all extremely low birth weight inants (1000 g.; ELBW) inants re-
ceive one or more blood transusions during their first weeks o lie. When a preterm inant
receives a blood transusions, the transused blood comes rom human adults. 12, 13Most o
the haemoglobin present in the erythrocytes o healthy adults is adult haemoglobin (HbA).
In preterm inants, however, most o the haemoglobin in the blood is o a different type,
etal haemoglobin (HbF). This HbF plays an important role in the oxygenation o the oe-
tus. Compared to HbA, HbF binds 2,3-DPG poorly. 2,3-DPG is an organophosphate, which
is created in the erythrocytes during glycolysis. High levels o 2,3-DPG shit the curve to the
right, while low levels o 2,3-DPG cause a letward shit. Thus, because HbF binds 2,3-DPG
Oxygensaturation(SO2)[%]
left shifted by:
pH
.-DPG
Temperature right shifted by:
pH
.-DPG
Temperature
Partial pressure of oxygen (PO2) [mmHg]
(7.5 mmHg = 1 kPa)
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Oxygenation in preterm infants
poorly, the level o 2,3-DPG in the blood o oetuses is relatively low. Consequently, the OD-
curve is shited letward compared to the HbA-rich blood o the mother. The letward shit
o the OD-curve represents a higher oxygen affinity compared to the mother. The higher
oxygen affinity o the blood in oetuses accounts or a better transer o oxygen in the blood
rom the mother to the oetus and or optimal oxygenation o the oetus under the rela-
tively hypoxic conditions in utero. Thus, in general, the higher the percentage o HbF in the
blood, the higher the SO2 level or a certain PO2 value, and vice versa. 14, 15
In healthy newborns, HbF is broken down and replaced by HbA in three to six months ater
birth. Nevertheless, this slow and regulated change o haemoglobin is not seen in preterminants in the NICU because o the blood transusions with HbA. A transusion with HbA
can speed up the natural process o haemoglobin change to only several hours, consequent-
ly causing a rapid right shit in the OD-curve (i.e. a decrease o oxygen affinity). Thereore,
it is advised to transuse blood with HbA slowly, and to monitor blood oxygen levels closely
during and ater the blood transusion.16-19
To keep both SaO2 and PaO2 within a certain range, accurate monitoring is required. In the
next part o this chapter the (dis)advantages o methods developed to monitor oxygenation
in preterm inants are discussed.
.MONITORING OF OXYGENATION
The aim o monitoring was very well described by Murkovic:20The primary aim of moni-
toring is to ensure that appropriate care or therapy can be given prior to the onset of complica-
tions. Thus, inormation obtained by monitoring equipment is important to alert or a
change in condition, and an aid or healthcare proessionals in the decision making.
The monitoring o preterm inants is challenging.20 Preterm inants lie in an incubator
with an air temperature around 35C and with a high humidity. Furthermore, the sensors
used or monitoring have to be small and user-riendly or the patient, their amily and the
healthcare proessionals. In neonatal care, this implicates that the sensors should, at least,
not hamper the development o the preterm inant.
Before the techniques for continuous monitoring became available, healthcare professionalscould only use physical assessment of the skin of the patient to determine their oxygenation.21
In the recent decades, several methods and sensors have been developed, with varying tech-
niques and functions to determine whether the total oxygen delivery achieves the total oxy-
gen demand in preterm infants. These techniques are discussed in the following paragraphs.
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CHAPTER
..PHYSICAL ASSESSMENT
For healthcare proessionals, changes in the skin colour o patients have always been an
important indication or changes in the oxygenation. Nowadays, this method is still used
to determine oxygen requirement in preterm inants. However, physical assessment o the
skin is a subjective method, and not very reliable in detecting both hypoxia and hyperoxia
in preterm inants.22-24Thereore, the possibility to perorm blood gas analysis was a huge
improvement in the assessment o oxygen requirement.
..BLOOD GAS ANALYSIS
In blood gas analysis, a small sample o blood, either arterial, venous or capillary (mixed)blood, is taken rom the patient. This blood sample is analysed to determine the adequacy
o ventilation, pulmonary gas exchange, and the acid-base status o the patient.25 Blood
gas analysis rom arterial blood provides multiple parameters like the SaO2, PaO2, arterial
carbon dioxide tension (PaCO2), pH, base excess, and ractions o different types o hae-
moglobin. Until the 1970s blood gas analysis was the only reliable method to determine
oxygen levels in the blood. Today, blood gas analysis is still the golden standard in medical
practice.
Unortunately blood gas analysis is not without drawbacks. Firstly, there is the loss o blood
each time a sample is needed (0.3 ml). In preterm inants each drop o blood is o high value
or the patient, thus the number o blood samples that is collected should be minimised.
Secondly, the percutaneous puncture can lead to agitation. Regrettably, the specially de-
veloped indwelling catheters to reduce percutaneous punctures are associated with vascular
complications and inection.26 The third disadvantage is the act that the method provides
only inormation about the moment the sample was taken. Thus, due to the intermittent
sampling, ast fluctuations in oxygenation could be missed.27, 28To overcome the lack o
inormation about oxygenation in between blood sampling, since the 1960s several groups
worked on the development o continuous measurement o blood oxygen levels.
..CONTINUOUS INTRAARTERIAL BLOOD GAS MONITORING
Continuous measurement o blood oxygen levels became possible because o the develop-
ment o catheters or continuous intra-arterial blood gas monitoring (CIBM). These CIBM
systems were designed to determine SaO2, PaO2, PCO2, and/or pH continuously and in-
vasively. Initially, the CIBM systems were thought to be able to give insight in the rapid
changes in blood oxygen levels, and reduce the need or blood sampling. These advantageswould enhance therapeutic decision making, and reduce the need or blood transusions.
Consequently, this would presumably lead to a reduction in the risks o inection, in work-
load o the caregivers, and in hospital costs.
The presumed advantages o CIBM systems were tested in animals, 29 adults,30 inants,31-37
and neonates.38-42 Various interesting review papers discuss the results o the developed
CIBM systems in detail.28, 43, 44Two o the most recent developed devices are the Paratrend,
and the Neotrend (Figure 2.3).29, 33-35, 41
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Oxygenation in preterm infants
FIGURE .Schematic drawing of the the Paratrend (Diametrics Medical, High Wycombe, UK). The sen-
sors for pH, PaCO2, PaO2 and the temperature are shown. This system was commercially available in the
1990s. Drawing is based on [].
The Paratrend consists o a hybrid probe (diameter 0.5 mm, length 4 cm) with thermocouple,
an electrochemical PO2 sensor, and absorbance sensors or pH and PCO2. The Neotrend is
based on the Paratrend, and especially designed or neonates.
Although the Paratrend, the Neotrend, and some other devices were commercially
available, none o them were widespread in clinical use. This was due to, amongst others,
the risk o inection, and the deposition o plasma proteins on the device. This deposition
leads to platelet activation, adhesion and thrombus ormation.42, 45-49Another problem was
the wall effect, a phenomenon where the PaO2 value suddenly drops. This drop is caused
by the act that the sensor is touching the arterial wall and measures the gas values o the
tissue instead o the blood.28, 43, 45Above that, the sensors o the CIBM systems need requent
recalibration,37, 39and are highly ragile.28, 43, 45
As ar as we know, today, sensors or intra-arterial measurement are not used in daily care
in NICUs anymore. However, in the uture, the development in materials, and the improve-
ment and miniaturization o techniques may increase new possibilities or CIBM systems.
..TRANSCUTANEOUS OXYGEN MEASUREMENTSimultaneously with the development o CIBM systems, transcutaneous oxygen measure-
ment became available. In 1956 L.C. Clark invented a polarographic membrane-covered
oxygen electrode.50When this Clark electrode is positioned on the chest o a patient it can
measure the diffusion o oxygen through the skin into the sensor. Based on this diffusion
the transcutaneous partial pressure o oxygen (tcPO2) and the transcutaneous partial pres-
sure o carbon dioxide (tcPCO2) can be determined.51This technique was the first, and still
the only, possibility to monitor PO2 and PCO2 continuous and transcutaneous.
Temperature
PO2
PCO2
pH
. mm
mm
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CHAPTER
In preterm inants, tcPO2 correlates well with the PaO2. Thereore transcutaneous oxygen
monitoring was rapidly accepted or routine use in neonatal intensive care.52However, soon
ater the introduction in clinical practice, it became clear that the accuracy o the measure-
ment declined when PaO2 increased, or when skin perusion was decreased.53, 54An adequate
skin perusion is required to obtain optimal diffusion o oxygen. To achieve adequate skin
perusion, the skin o the preterm inant needs to be heated to approximately 43 - 44C. Un-
ortunately, heating up the weak skin o preterm inants can lead to erythema. To prevent
this side effect, the sensor needs to be repositioned and recalibrated every 3 to 4 hours. This
repositioning and recalibration causes a high workload or the nursing staff.52, 55, 56
The necessity for heating of the skin, the high workload of the technique, the relative large
and heavy sensor, and the development of a newer technique pulse oximetry are the reason
that transcutaneous oxygen monitoring is not used very often anymore in the NICU.56, 57
..PULSE OXIMETRY
Pulse oximetry was invented in Japan in the 1970s by T. Aoyagi. 58The technique was first
introduced in perioperative care, but it soon expanded into (neonatal) intensive care units.
Pulse oximetry w