Original Article
A Crossover Analysis of Mandatory Minute Ventilation Compared
to Synchronized Intermittent Mandatory Ventilation in Neonates
Scott O. Guthrie, MD
Chris Lynn, RRT
Bonnie J. LaFleur, PhD
Steven M. Donn, MD
William F. Walsh, MD
BACKGROUND:
Mandatory minute ventilation (MMV) is a novel ventilator mode that
combines synchronized intermittent mandatory ventilation (SIMV)
breaths with pressure-supported spontaneous breaths to maintain a
desired minute volume. The SIMV rate is automatically adjusted to
maintain minute ventilation.
OBJECTIVE:
To evaluate MMV in a cohort of infants without parenchymal lung disease
alternately ventilated by MMV and SIMV.
DESIGN/METHODS:
Neonates >33 weeks’ gestational age and electively intubated for medical
or surgical procedures were enrolled. Exclusionary criteria included:
nonintact respiratory drive or active pulmonary disease. Infants were
randomized to receive 2 hours of either SIMV or MMV and then crossed
over to the other mode for 2 hours. Ventilator parameters and end-tidal
CO2 (etCO2) were measured via inline, mainstream monitoring and
recorded every minute.
RESULTS:
In total, 20 infants were evaluated. No statistically significant differences
were found for overall means between etCO2, minute volumes, peak
inspiratory pressure (PIP), or positive end expiratory pressure (PEEP).
However, there was a significant difference in the type of ventilator breaths
given and in the mean airway pressure. Additionally, there was a
statistically significant negative trend in MMV over time compared to
SIMV, although this was subtle and could have been due to extreme cases.
Department of Pediatrics (S.O.G., C.L., W.F.W.), Division of Neonatology, Vanderbilt University
School of Medicine, Nashville, TN, USA; Department of Biostatistics (B.J.L.), Vanderbilt University
School of Medicine, Nashville, TN, USA; and Department of Pediatrics (S.M.D.), Division of
Neonatal-Perinatal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.
Address correspondence and reprint requests to Scott O. Guthrie, MD, Department of Pediatrics,
Division of Neonatology, Vanderbilt University Medical Center, A-0126 MCN, Nashville, TN
37232-2370, USA.
CONCLUSIONS:
Neonates with an intact respiratory drive can be successfully managed
with MMV without an increase in etCO2. While this mode generates
similar PIP and PEEP, the decrease in mechanical breaths and the mean
airway pressure generated with MMV may reduce the risk of some of the
long-term complications associated with mechanical ventilation.
Journal of Perinatology (2005) 25, 643–646. doi:10.1038/sj.jp.7211371;
published online 4 August 2005
INTRODUCTION
Mandatory minute ventilation (MMV) is a mode of ventilation that
combines features of synchronized intermittent mandatory
ventilation (SIMV) and pressure support ventilation (PSV). This
mode of ventilation is theoretically a more intuitive approach to
ventilator management. In MMV the mandatory ventilator rate is
varied based upon the patient’s needs rather than delivering a
constant preset rate. In MMV, the clinician chooses a minimum
minute volume (the product of tidal volume and frequency) for the
patient. If the patient’s spontaneous breathing, which is augmented
with PSV, meets or exceeds this minute volume, no mandatory
ventilator breaths are provided. If, however, the patient’s minute
volume falls below the preselected minimum, the ventilator will
provide ‘‘catch up’’ breaths at a fixed frequency to ensure that the
patient receives this preselected minute ventilation.
This mode was first described in the adult literature in 1977 and
has been shown to be successful in ventilator weaning.1,2 Advances
in microprocessor technology have recently allowed this mode to be
adapted to neonatal ventilators. Its use in the newborn was first
reported by Donn and Becker.3 There are, however, no clinical
studies to evaluate the use of this mode in neonates. The purpose
of this study was to compare MMV and SIMV with respect to carbon
dioxide removal and other ventilator parameters using a crossover
design. The null hypothesis was that there would be no differences
in carbon dioxide removal or other ventilatory parameters in
infants alternately ventilated with MMV or SIMV.
METHODS
Patient Inclusion Criteria
Infants were eligible for the study if they were >33 weeks’
gestational age by obstetrical dating criteria. Infants who were
Journal of Perinatology 2005 25:643–646
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Guthrie et al.
electively intubated for medical or surgical procedures and who
returned to the NICU still intubated for post-procedural care were
considered eligible.
Patient Exclusion Criteria
Infants were excluded if they had known lung disease, if they had
sustained a neurologic insult, or if they required a level of sedation
that would interfere with spontaneous respiratory drive.
Study Approval
The study was approved by the Vanderbilt University Medical
Center’s Institutional Review Board. Informed consent was
obtained from parents before enrollment.
Draeger Evita 4 Ventilator
The Draeger Evita 4 Ventilator (Draeger Medical Inc., Luebeck,
Germany) is a time cycled, constant volume, long term, intensive
care multi-modality ventilator for adult, pediatric, and neonatal
patients. When a patient is placed in MMV, the ventilator allows
spontaneous breathing, which can be augmented by PSV, and
provides automatic adjustments of the SIMV rate to the meet the
preset minimum minute volume chosen by the clinician. If the
patient maintains the set minute volume, no mandatory breaths
are delivered. The breaths that are delivered will be pressuresupported breaths that are flow cycled and will allow the baby to
determine their own inspiratory flow and time. If the patient’s
minute volume is insufficient, mandatory delivery of the preset
tidal volume will occur at fixed intervals until the desired minute
volume is achieved. These breaths will be mandatory mechanical
breaths that have a fixed flow and inspiratory time. Determinations
of the need for mandatory breaths are made every 7.5 seconds.
Should apnea follow a period in which the spontaneous minute
volume was high, the Evita 4 will wait a maximum of 7.5 seconds
plus one cycle time before beginning mandatory breaths.
Measurement of etCO2
The CO2SMO Plus Respiratory Profile Monitor (Novametrix Medical
Systems, Inc., Wallingford, CT) is a continuous, noninvasive
capnometer that uses a mainstream sensor to measure end-tidal
carbon dioxide. It employs a single beam, nondispersive infrared
absorption, radiometric measurement to calculate the partial
pressure of carbon dioxide in the expired air (etCO2). Since the
absorption is proportional to the concentration of the absorbing
molecule, the concentration can be determined by comparing its
absorption to that of a known standard. Therefore, no
compensation is required when different concentrations of nitric
oxide, oxygen, anesthetic agent, or water vapor are present in the
inhaled or exhaled breath. A fixed orifice, neonatal sensor
(Novametrix Medical Systems, Inc.) was attached to the existing
ventilator circuit. This added 0.7 ml of dead space to the circuit.
After a 10-second self-test, the sensor was attached between the
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Mandatory Minute Ventilation
endotracheal tube and the ventilator circuit. The monitor was then
linked to a computer and measurements were recorded every
minute by the Analysis Plus Software Package, Version 5.0
(Novametrix Medical Systems, Inc.).
Study Design
A crossover study design was used to compare the ventilatory
modes. Patients were randomized to receive either SIMV or MMV as
the initial ventilator mode. The study began at least 4 hours after
the infant returned from surgery and only after adequate
spontaneous respiratory effort was demonstrated while the baby was
ventilated in SIMV. A blood gas was obtained to demonstrate that
the prestudy set minute volume (between 150 and 250 cm3/kg/
min) was ventilating the baby adequately. The capnograph was
then attached to the ventilator circuit. To adjust for the dead space
added by this sensor, an additional 1 cm3 of tidal volume was
added to the tidal breaths the baby was already receiving. The Evita
4 measures tidal volume proximal to the endotracheal tube and
automatically calculates and adjusts with pressure support for the
dead space of this sensor and the endotracheal tube. EtCO2 was
measured continuously for 2 hours during the initial mode of
ventilation. During this time, a computer recorded the etCO2
reading and other ventilator parameters every 60 seconds. At the
end of 2 hours only the infant’s mode of ventilation was switched.
No other parameters were adjusted. After a 15-minute equilibration
period, data collection resumed and continued for 2 hours. The
SpO2 and blood pressure were also monitored continuously.
In the MMV mode, ventilatory settings were adjusted to provide a
tidal volume breath of 4–6 cm3/kg in both SIMV and PSV. Peak
inspiratory pressure (PIP) was variable based on the lung
compliance and baby’s efforts. Positive end expiratory pressure
(PEEP) was set at 5 cmH2O in both SIMV and MMV and the desired
minute volumes were identical in both modes.
Statistical Analysis
A sample size calculation for equivalence in means was performed
before study commencement. We wanted to ensure we had
adequate power to detect reliable small differences such that
negative findings would not be due to inadequate sample size. With
20 infants, we estimated 81% power to detect a 2.5 mmHg paired
difference in etCO2 between ventilators at the 0.05 level of
significance (assuming a paired standard deviation of 2.8).
Profile analysis was used to compare paired ventilatory mode
outcomes. A linear regression analysis was performed on each
outcome of interest (etCO2, minute volume, PIP, PEEP, type of
ventilator breaths given, and mean airway pressure ðpawÞ) over
time for each subject. The time-centered intercept differences
between MMV and SIMV values were compared using a paired ttest. To examine how MMV and SIMV values change over time, the
paired slope differences were tested. Analyses were performed with
SAS, version 9 (SAS Institute, Inc., Cary, NC) and R, version 2.01
Journal of Perinatology 2005 25:643–646
Mandatory Minute Ventilation
Guthrie et al.
Table 1 Patient Characteristics
Diagnosis
Number
GA (weeks)
Weight (g)
Vent hours at start of study
Gastroschisis
Tracheoesophageal fistula
Congenital heart defect
Myelomeningocele
6
4
4
2
Encephalocele
Meconium ileus
Micrognathia
Volvulus
1
1
1
1
38 (1)
38 (1)
38 (2)
38
38
40
35
36
35
2850 (288)
2721 (228)
2781 (603)
4055
3900
3600
3990
2970
2400
88 (105)
30 (28)
29 (15)
22
24
144
72
336
28
Mean (SD) for variables when appropriate.
for Windows (R Foundation for Statistical Computing, Vienna,
Austria).
Table 2 Paired Differences in Overall Mean Values
Mode
p-Value*
MMV
SIMV
etCO2
Mean
SD
41.93
6.99
41.98
7.00
0.90
PIP (cmH20)
Mean
SD
11.05
3.74
11.62
2.52
0.13
PEEP (cmH20)
Mean
SD
5.21
0.43
5.24
0.47
0.45
Paw (cmH20)
Mean
SD
6.29
0.71
6.65
0.71
<0.05
46.59
14.99
49.73
15.50
0.11
Mechanical breaths (per minute)
Mean
SD
4.06
9.07
24.23
4.82
<0.05
Spontaneous breaths (per minute)
Mean
SD
42.53
18.07
25.50
15.73
<0.05
0.77
0.26
0.78
0.25
0.78
RESULTS
The study was conducted from July to November 2004 in the
Neonatal Intensive Care Unit of the Monroe Carell, Jr. Children’s
Hospital at Vanderbilt. In total, 20 infants completed the study. One
infant self-extubated prior to the completion of data collection and
was omitted from analysis.
Characteristics of patients enrolled are shown in Table 1. The pvalues for the average difference between MMV and SIMV for each
subject are demonstrated in Table 2. The individual regression
lines for all subject’s etCO2 trends are displayed in Figure 1.
DISCUSSION
This study shows that MMV of the neonate appears to be as safe
and equally efficacious at removing carbon dioxide as SIMV. While
this mode generates similar PIP and PEEP, the decrease in
mechanical breaths and the Paw generated with MMV may reduce
the risk of some of the long-term complications associated with
mechanical ventilation. Among the cohort of infants studied, a
consistent reduction in mechanical support was achieved with
MMV in comparison to SIMV, with a significant reduction in the
number of mechanical breaths. This decrease in mechanical
assistance resulted in a concomitant decrease in Paw. These
findings are similar to those of Claure et al.4
Like every mode of ventilation, MMV has potential limitations.
During periods of very fast (>80 breaths per minute), but shallow
spontaneous breathing, the measured minute volume may meet or
exceed the targeted minute volume and due to increased
ventilation of dead space may result in decreased alveolar minute
ventilation. The ventilator may then reduce the mechanical rate
and provide only pressure-supported breaths. This situation could
Journal of Perinatology 2005 25:643–646
Total breaths (per minute)
Mean
SD
Total minute volume (l/kg)
Mean
SD
*p-Values are based on paired t-test.
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Guthrie et al.
Mandatory Minute Ventilation
achieved in small infants with pulmonary disease, without losing
residual volume, this could prove to be less injurious to both the
neonatal lung and brain.
Limitations of this study include small sample size, the inability
to blind, short duration of monitoring, and a homogenous
population. Although a prestudy statistical analysis was performed,
it is possible that sample size may have been too small to detect a
true difference in outcome over a longer duration of time. Since
this was a pilot study examining a new mode of ventilation, we
chose to examine MMV in a population of babies with normal
lungs and respiratory drive, so as to remove confounders which
might make interpretation of data more difficult in view of
impaired gas exchange. Until further studies have been completed
in infants with active lung disease, we urge caution in using this
mode. In summary, in this pilot study, MMV was found to be
similar to SIMV in ventilatory parameters and in removing CO2.
Future studies of MMV in infants of younger gestational ages and
with various lung diseases appear warranted and should address
these issues.
Figure 1. Linear regression for etCO2 levels for each subject.
lead to alveolar collapse. The clinician, therefore, needs to pay
close attention to the infant’s respiratory rate when using this
mode. It is also possible that the decrease in Paw and resultant loss
in functional residual capacity with MMV could adversely affect
infants with lung disease. The study of Olsen et al.5 involving PSV,
found this to be a potential complication when a PEEP lower than
five was used.5,6 We sought to prevent this from happening by
using a higher PEEP to maintain the Paw. As with any form of
triggered ventilation, underlying metabolic acidosis may also drive
the baby’s spontaneous rate to achieve compensatory respiratory
alkalosis.
MMV enables the baby to breathe with nominal ventilator
support if they are able to generate the minimum minute
ventilation. Successful ventilation in this mode may lead to more
expedient weaning with only the PEEP, pressure support, and FiO2
to adjust, thus decreasing the need for blood gas monitoring. In
the baby with an intact respiratory drive this would be
advantageous as there may be less variance in arterial CO2 tension
than with SIMV. In addition, if a more stable arterial CO2 can be
646
Acknowledgements
We are grateful for the assistance of the respiratory therapy staff and nursing staff
at Vanderbilt Children’s Hospital who assisted in this study.
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