Original Article
Effect of Volume Guarantee Combined with Assist/Control vs
Synchronized Intermittent Mandatory Ventilation
Kabir Abubakar, MD
Martin Keszler, MD
OBJECTIVE:
To compare the effect of combining assist/control with volume-guarantee
(AC þ VG) vs synchronized intermittent mandatory ventilation with VG
(SIMV þ VG) on tidal volume (VT), peak inspiratory pressure (PIP),
mean airway pressure (MAP), respiratory rate, heart rate, oxygen
saturation (SpO2), and minute volume (MV) in preterm infants.
STUDY DESIGN:
A total of 12 infants were randomized to receive AC þ VG, followed by
SIMV þ VG, or the opposite sequence for four alternating 2-hour periods.
RESULTS:
Airway pressure of machine breaths was higher during SIMV. MV and VTe
were similar, but more variable during synchronized intermittent
mandatory ventilation. The VTe of unsupported breaths during SIMV was
lower than machine breaths of SIMV and AC. There was more tachycardia
and tachypnea with a lower and more variable SpO2 during SIMV.
CONCLUSIONS:
SIMV þ VG is associated with higher work of breathing indicated by
tachycardia, tachypnea and lower SpO2 compared to AC þ VG. VG appears
to be more effective when combined with AC than with SIMV.
Journal of Perinatology (2005) 25, 638–642. doi:10.1038/sj.jp.7211370;
published online 11 August 2005
BACKGROUND
For more than three decades, neonatal ventilatory support has
consisted of time-cycled pressure-limited ventilation with its
associated complications of patient-ventilator asynchrony resulting
in inefficient gas exchange, air leaks and increased risk of
Division of Neonatology , Department of Pediatrics, Georgetown University Children’s Medical
Center, Washington, DC, USA.
Supported in part by a grant from Dra¨ger Inc.
Address correspondence and reprint request to Kabir Abubakar, MD, Division of Neonatology,
M3400, Georgetown University Children’s Medical Center, Washington, DC 20007, USA.
638
Simv no soporta cada respiración
intraventricular hemorrhage.1,2 With improved microprocessor
technology, synchronized modes of conventional mechanical
ventilation have become available for neonatal ventilatory support.
The principal advantages of synchronized mechanical ventilation,
namely decreased work of breathing, greater patient comfort, less
need for sedation and facilitation of the weaning process, have
been well documented in adult and pediatric patients.3–7 Even
though there have been few studies in newborn infants,8–16 there
is now widespread acceptance of synchronized mechanical
ventilation in newborn intensive care. The two most widely used
modalities of synchronized mechanical ventilation are
synchronized intermittent mandatory ventilation (SIMV) and
assist/control (AC). SIMV provides a preset number of mechanical
breaths as in standard intermittent mandatory ventilation (IMV),
but these are synchronized with the infant’s spontaneous
respiratory effort. However, spontaneous breaths in excess of the
preset number are not supported. In AC, every spontaneous breath
is supported by the ventilator.
It is now clear that volume is an important contributor to
ventilator-induced lung injury,17,18 and as such, there is a growing
interest in directly controlling tidal volume (VT) during
mechanical ventilation in infants. New technologies have allowed
modifications of time-cycled, pressure-limited ventilators designed
to target a set tidal volume by microprocessor-directed adjustments
of peak pressure or inspiratory time. Volume guarantee (VG) is one
such mode available on the Dräger Babylog 8000plus (Dräger,
Lübeck, Germany) that may be combined with any standard
synchronized mode. In VG mode the ventilator servo-controls the
peak inspiratory pressure (PIP), within preset limits, to achieve the
operator-preset target VT. In this way, the ventilator automatically
compensates for changes in lung compliance, airway resistance
and patient spontaneous respiratory effort to maintain the set VT,
effectively combining the advantages of volume controlled and
pressure limited ventilation. VG only controls the VT of the
mechanical breaths. With AC, all breaths are mechanically
supported and consequently, all breaths are subject to VG auto-
regulation of VT. With SIMV, only the IMV breaths are volume-
regulated. Volume guarantee has been shown to be feasible in
infants.19,20 Recent studies have documented a decreased incidence
of hypocarbia and inappropriately large or small VT when VG is
combined with AC, compared to AC alone,21 and significantly lower
variability of delivered VT with VG, compared to AC or SIMV
alone.22 However, the relative advantages of combining VG with AC
vs VG with SIMV have not been examined.
Journal of Perinatology 2005; 25:638–642
r 2005 Nature Publishing Group All rights reserved. 0743-8346/05 $30
www.nature.com/jp
Volume Guarantee Ventilation
Our objective was to compare the effect of VG combined with
AC and VG combined with SIMV on the stability of VT, oxygen
saturation, respiratory rate (RR), heart rate (HR) and airway
pressures in preterm infants requiring mechanical ventilation. We
hypothesized that exhaled tidal volume (VTe), oxygen saturation
and minute ventilation (MV) will be more stable when VG is
combined with AC, compared to VG combined with SIMV.
METHODS Exclusión
Patients
A total of 12 clinically stable premature infants receiving support
with mechanical ventilation were studied. Infants who had a
significant endotracheal tube leak (>30% leak does not allow for
accurate VTe measurement), required heavy sedation, muscle
paralysis or had significant congenital cardiac, respiratory or
central nervous system malformations were excluded. The study
was approved by the Georgetown University Institutional Review
Board and informed consent was obtained from all parents before
study entry.
Study Design
This was a crossover study with each patient serving as his/her own
control. Infants were randomly assigned using a table of random
numbers to receive AC ventilation with VG (AC þ VG) first, followed
by SIMV with volume guarantee (SIMV þ VG), or the opposite
sequence for four alternating 2-hour periods (total study time of
8 hours). Before each study mode was applied, each infant was
returned to his/her baseline ventilation mode for a period of 20
minutes to avoid any crossover effects from one study mode to
another.
Ventilator Management
All infants were ventilated using the Babylog 8000plus Software
version 5 with Volume Guarantee module (Dräger, Lübeck,
Germany). The VG mode is a volume-targeted, time-cycled,
pressure-limited form of ventilation. The operator chooses a target
VT and selects a pressure limit up to which the ventilator operating
pressure (the working pressure) may be adjusted. The
microprocessor compares the VT of the previous breath, using
exhaled tidal volume (VTe) to minimize possible artefact due to
endotracheal tube leak, and adjusts the working pressure up or
down to achieve the set VT. In both the AC and SIMV modes, the
target VT was set at 5 to 6 ml/kg. The PIP limit was then set 15%
above the PIP needed to achieve the target VT. The PIP limit was
adjusted upward in increments of 1 to 2 cmH2O if the actual PIP
generated by the ventilator (the working PIP) is repeatedly
reaching the PIP limit and/or the set VT could not be achieved with
the current PIP limit. In both modes, the ventilator rate was set at
30 breaths per minute throughout. Inspiratory time was set at 0.3
to 0.35 seconds and positive end-expiratory pressure at 5 to
Journal of Perinatology 2005; 25:638–642
Abubakar and Keszler
7 cmH2O, both remained unchanged throughout the study.
Fraction of inspired oxygen (FiO2) was adjusted to maintain
oxygen saturation target range of 88 to 92% according to our unit
protocol. Blood gas measurements were obtained by the clinical
team only as needed. However, no ventilation settings or FiO2
needed to be changed in any patient as a result of an undesired
blood gas value.
Data Acquisition and Analysis
Demographic information. Demographic information was
extracted from the infant’s and mother’s chart and entered into the
patient database.
Ventilator variables. Ventilator variables for every breath were
recorded from the ventilator pressure and volume-monitoring
module continuously using proprietary software (Lufu3, Dräger,
Lübeck, Germany) and then exported into a spreadsheet (Microsoft
Excel, Microsoft Corporation, Redmond, WA) for initial analysis.
These variables included RR, airway pressures (PIP recorded is the
actual pressure, not the pressure limit), FiO2, VTe, and MV. All
breaths were examined manually and those that manifested severe
distortion, large negative leak (VTe much larger than inspiratory
VT) or other obvious artifact, such as would result from handling,
movement or hiccups were deleted following preset criteria to
obtain a truer reflection of the ventilator performance. Criteria for
breath exclusion included difference between inspiratory and
expiratory VT >40%, and inspiratory time <0.1 or >1 second
(indicating that the values did not represent a true breath).
Exhaled tidal volume, which is less affected by leak around the
endotracheal tube, was used for analysis.
Pulse oximetry. Oxygen saturation and HR were continuously
recorded using an Ohmeda Biox 3740 pulse oximeter
(Datex-Ohmeda Inc., Madison, WI). The oximeter stores the
readings in memory; these were then downloaded onto a
personal computer for analysis using Profox Oximetry software,
(Profox Associates, Inc., Escondido, CA). Oxygen saturation
measurements that did not correlate with a HR measurement
were determined to be a result of movement artefact and were
excluded from analysis.
Data analysis. Measurements of tidal volume, PIP,
mean airway pressure (MAP), MV, RR, HR and oxygen saturation
computed for each patient at each study period were compared
using paired t-test. Variability for these same parameters was
analyzed using ANOVA for repeated measures. All statistical
analyses were done using Minitab 14 statistical software.
(Minitab Inc., PA). Statistical significance was considered at
p<0.05.
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 Abubakar and Keszler Volume Guarantee Ventilation

RESULTS
A total of 12 infants requiring mechanical ventilation who met the
study criteria were enrolled. All infants successfully completed the
study. All infants had received a full course of antenatal
betamethasone prior to delivery. The baseline characteristics of the
infants at time of study entry are shown in Table 1. Ventilator and
cardio-respiratory parameters discussed below are shown in Tables
2 and 3.
PIP and mean airway pressures were significantly higher with
machine-supported breaths of SIMV þ VG compared to AC þ VG
(Table 2). MV (all breaths included) and VTe were similar in the
two groups, but both were significantly more variable during
SIMV þ VG compared to AC þ VG. The VTe of machine-supported
breaths during SIMV þ VG was similar to that of AC þ VG by
design since the same tidal volume was targeted in both modes.
However, the VTe of unsupported breaths during SIMV þ VG was
significantly lower and more variable than that of machine
supported breaths during SIMV þ VG or the VTe during AC þ VG
(Table 2).
During SIMV þ VG, the infants had a faster and more variable
RR than while on AC þ VG. Similarly, the HR was higher and
more variable while infants were on SIMV þ VG. Even though FiO2
remained unchanged across study modes, oxygen saturation was
significantly lower and much more variable during SIMV þ VG
than AC þ VG (Table 3).
DISCUSSION
Although the physiologic advantages of synchronized mechanical
ventilation have been well documented, there is no clear consensus
on which of the two most commonly used synchronized ventilation
modes is superior. Prior studies have shown that AC facilitates
weaning from mechanical ventilation and delivers more consistent
tidal volume with less fluctuation in blood pressure when
compared to SIMV.13–16 Adding volume guarantee to either mode
of synchronized conventional ventilation has been shown to
provide more uniform tidal volume delivery.22 The purpose of this
study was to compare the effect of adding volume guarantee to
Table 3 Heart Rate, Respiratory Rate and Oxygenation
AC+VG SIMV+VG p-value

Heart rate Mean±SD 148±5 161±7 p<0.0001

Table 1 Demographic Characteristics of Studied Infants (beats/minute) Variance 25 46 p<0.0001

Mean (SD) Range

Respiratory rate Mean ±SD 55.1±6.4 65±8 p<0.0001
Gestational age (week) 26 (2.4) 24–33 (breaths/minute) Variance 44.0 70.0 p<0.01
Birth weight (g) 679 (138) 525–870
Study weight (g) 887 (247) 690–1535 Oxygen saturation (%) Mean ±SD 95±2 91±3 p<0.0001
Age at study (days) 27 (17) 7–59 Variance 3 12 p<0.0001

Table 2 Ventilator Variables

AC+VG All SIMV breaths SIMV+VG machine SIMV spontaneous p-value
breaths breaths

PIP (cmH2O) Mean±SD 15±4.1* 14±4.8 17±2.9* p<0.001*

Variance 17.9* 24.4 9.5* p<0.001*

MAP (cmH2O) Mean±SD 8.6±1.8* 8.2±2 9.3±1.6* p<0.004*

Variance 3.4 4.0 2.7 p<0.001w

Exhaled tidal volume (ml) Mean±SD 5.2±0.5 4.9±2.0 5.1±1.8 3.2±1.8 p<0.001w
Variance 0.3 4.4 3.4 3.5 p<0.0001z

Minute volume (ml) Mean±SD 328±50 319±78 NS

Variance 348 652 p<0.001
*AC+VG compared to SIMV+VG machine breaths only.
w
Spontaneous unsupported SIMV breaths compared to AC+VG and SIMV+VG (total and machine breaths).
z
AC+VG compared to SIMV+VG spontaneous or machine supported breaths.

640 Journal of Perinatology 2005; 25:638–642

Volume Guarantee Ventilation
assist control ventilation on the stability of tidal volume delivery,
MV, airway pressures, oxygen saturation and RR compared to SIMV
with VG.
We found that adding volume guarantee to AC ventilation
results in more uniform tidal volume delivery with less
breath-to-breath fluctuation compared to SIMV þ VG. We
suggest that this is because with AC, every spontaneous breath
is subject to volume regulation, whereas in SIMV only the
machine breaths are supported and any un-supported breaths
taken by the infant are not subject to volume guarantee. The
algorithm of the VG software limits the magnitude of pressure
increase from one breath to the next to approximately 3 cmH2O
to avoid potentially dangerous overshoot. Consequently, when
the VTe falls much below the target, several breaths are needed
to achieve the target VTe. Since fewer breaths are subject to
volume regulation in SIMV, more time is needed to reach
target value and larger fluctuations are likely as the infant’s
spontaneous respiratory effort fluctuates.
Small preterm infants with respiratory failure who require
mechanical ventilation typically cannot generate adequate VT on
their own. This in part reflects their poor lung compliance, the
high airway resistance of small endotracheal tubes, inadequate
muscle strength and unfavorable mechanics of the immature chest
wall. Consequently, when ventilated by SIMV, the unsupported
spontaneous breaths are often quite small, resulting in limited
effective alveolar ventilation. In SIMV mode, the limited number of
ventilator breaths must make up for the inefficient spontaneous
breaths by using larger VT. In AC, each breath is supported;
therefore, the ventilator cycles at a faster rate and thus a smaller
VT is required to maintain equal MV, when compared to SIMV.16
When SIMV is used in pressure-limited mode, the larger ventilator
VT is generated with somewhat higher inspiratory pressure.
When the VT is fixed at an equal value by the use of VG in
combination with SIMV, the only mode of compensation available
is for the infant to breathe more rapidly, as was seen in our
study population.
We were surprised to see that in SIMV, compared to AC, higher
PIP was needed to generate the same VTe. Two possible
explanations present themselves. One is that the slower rate of
‘‘normal’’ sized unsupported breaths allowed enough time for
atelectasis to develop, thereby leading to decreased lung
compliance. This appears unlikely, as the ventilator rate was set at
30 in SIMV mode, a time interval not likely to allow for atelectasis.
The observation that the infants were more tachypneic, with a
faster HR and had consistently lower oxygen saturations suggests
that the infants had substantially higher work of breathing during
SIMV. In that situation, we speculate that the infants were tiring
and therefore making a smaller contribution to each mechanical
breath. Given that the VT of a synchronized breath is determined by
the combined positive pressure of the ventilator and the negative
inspiratory pressure generated by the infant (the transpulmonary
Journal of Perinatology 2005; 25:638–642
Abubakar and Keszler
pressure), it follows that the ventilator contribution would need to
be higher in order to compensate. This appears to be the more
plausible explanation for the higher working pressure needed
during SIMV to generate identical VTe to AC.
Our findings are in keeping with earlier studies that have
demonstrated lower respiratory rates smaller and more consistent
VT and less fluctuation in blood pressure with AC, compared
to SIMV.13–16 An important finding in our study is the lower
oxygen saturation and the degree with which it fluctuates
during SIMV þ VG. This increased fluctuation in blood pressure
and oxygen saturation can be deleterious especially in smaller
infants at risk of intraventricular hemorrhage and retinopathy
of prematurity. We have shown in this study that adding VG
to AC rather than SIMV may add to the advantages of AC
over SIMV.
During our data analysis, all breaths were examined manually
and those that manifested severe distortion, large negative leak
(VTe much larger than inspiratory VT) or other obvious artifact,
such as would result from handling, movement or hiccups were
deleted following pre-set criteria to obtain a truer reflection of
the ventilator performance. On clinical observation, infants are
occasionally noted to have an interrupted expiratory pattern on the
ventilator. Some of these interrupted expiratory patterns may
appear as a distorted breath during manual examination of the
particular breath, resulting in that breath being excluded from
analysis. However, the number of excluded breaths was small and
analysis of both the raw data and data with distorted breaths
removed did not alter the results.
It should be recognized that the differences between SIMV
and AC observed in this study are likely to be more pronounced
with slower SIMV rates. During the acute phase of RDS when
more rapid SIMV rates are commonly used, there may be little
difference between the effectiveness of these modes with or
without VG. However, because many infants are exposed to
low SIMV rates for substantially longer periods of time during
weaning, our findings are applicable to the majority of infants
on SIMV.
This is a short-term crossover study in a small number of
infants to evaluate the immediate effects of adding VG to SIMV or
AC and was not designed to look at long-term differences between
these ventilation modes. However, our findings and those of
previous authors suggest that adding VG to assist control
ventilation would provide more gentle ventilation than SIMV þ VG
in small infants, especially during weaning. Available evidence does
not support the reluctance of many clinicians to accept AC as a
weaning mode. In the absence of an appropriately designed
prospective randomized trial, however, no conclusions can be
drawn about the long-term benefits of AC þ VG over SIMV þ VG
particularly looking at air-leak syndromes, duration of mechanical
ventilation, chronic lung disease and neuro-developmental
abnormalities.
641
 Abubakar and Keszler
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