Validation of predictors of extubation success and failure in

mechanically ventilated infants and children

Shekhar T. Venkataraman, MD, FAAP; Nadeem Khan, MD; Andrew Brown, RRT

Objective: To validate predictors of extubation success and
failure in mechanically ventilated infants and children by using
bedside measures of respiratory function.
Design: Prospective, descriptive study.
Setting: A university-affiliated children’s hospital with a 51-
bed critical care area.
Patients: All infants and children who were mechanically ven-
tilated for >24 hrs except neonates <37 wks gestation and
patients with neuromuscular disease.
Interventions: None.
Measurements and Methods: Extubation failure was defined as
reintubation within 48 hrs of extubation in the absence of upper
airway obstruction. Failure rates were calculated for different
ranges (selected a priori) of preextubation measures of breathing
effort, ventilator support, respiratory mechanics, central inspira-
tory drive, and integrated indices useful in adults. Effort of spon-
taneous breathing was assessed by the respiratory rate standard-
ized to age, the presence of retractions and paradoxic breathing,
inspiratory pressure, maximal negative inspiratory pressure, ratio
of inspiratory pressure to maximal negative inspiratory pressure,
and tidal volume indexed to body weight of a spontaneous breath.
Ventilator support was measured by FIO2, mean airway pressure,
oxygenation index, and the fraction of total minute ventilation
provided by the ventilator. Respiratory mechanics was assessed
by peak ventilatory inspiratory pressure and dynamic compliance.
Central inspiratory drive was assessed by mean inspiratory flow.
Frequency to tidal volume ratio and the CROP (compliance, rate,
oxygenation, and pressure) indexed to body weight, the integrated
indices useful in predicting extubation failure in adults, were also
calculated. A regression test for a linear trend in proportions was
performed with preselected ranges and the corresponding failure
rates. The failure rates from this study (validation group) were
compared to those published previously (prediction group) by the
chi-square test for proportions. The distribution of categorical
variables between groups was analyzed by using the chi-square
test or the Fisher’s exact test, and p < .05 was considered
significant.
Main Results: The study involved 312 patients. There were no
differences in any of the clinical characteristics between the
prediction and validation groups. The reasons for reintubation
were similar in both groups. Preextubation data were also similar
between the two groups. There were no differences between the
prediction and the validation groups in failure rates with different
ranges. There were no differences in the failure rates for any of
the cutoff values for peak ventilatory inspiratory pressure, mean
airway pressure, FIO2, oxygenation index, dynamic compliance,
tidal volume indexed to body weight of a spontaneous breath,
fraction of total minute ventilation provided by the ventilator, and
mean inspiratory flow.
Conclusions: Bedside measures of respiratory function can
predict extubation success and failure in infants and children.
Both a low risk and a high risk of failure can be determined by
using these measures. Integrated indices useful in adults do not
reliably predict extubation success or failure in infants and chil-
dren. Our study validates our previously published study. (Crit
Care Med 2000; 28:2991–2996)
KEY WORDS: extubation failure; mechanical ventilation; infants;
children

M echanical ventilation is dis-
continued and patients are
extubated when the under-
lying reasons for intuba-
tion and mechanical ventilation have re-
From the Departments of Anesthesiology/Critical
Care Medicine, University of Pittsburgh, and the De-
partment of Respiratory Care, Children’s Hospital of
Pittsburgh, Pittsburgh, PA.
Presented, in part, at the Annual Meeting of the
Society of Critical Care Medicine, 1998, San Antonio, TX.
Supported, in part, by grant 5M01 RR00084 from
General Clinical Research Center, National Institutes of
Health.
Address requests for reprints to: Shekhar T.
Venkataraman, MD, Children’s Hospital of Pittsburgh,
3705, Fifth Avenue, Rm 6840, Pittsburgh, PA 15213.
Copyright © 2000 by Lippincott Williams & Wilkins
solved and patients are judged to be
capable of sustaining spontaneous venti-
lation. Extubation failure, defined as re-
intubation and reinstitution of mechani-
cal ventilation, has been reported to
occur at rates of 17% to 19% in adults,
22% to 28% in premature neonates, and
16.3% in infants and children (1–5). A
number of variables have been validated
to predict weaning and extubation suc-
cess in adults (6 –17). We recently pub-
lished the relative risk of extubation fail-
ure in children based on measures of
respiratory function (5). We identified
threshold values for certain simple bed-
side measures of respiratory function that
defined a low risk (ⱕ10%) and a high risk
(ⱖ25%) of extubation failure (5). During
the first study, we found that the use of
pressure support and other forms of as-
sisted ventilation such as volume support
was not widespread. Since our first study,
we have observed that the use of assisted
ventilation such as pressure support and
volume support has increased consider-
ably during weaning in children. There
are currently no studies that show
whether using assisted ventilation affects
weaning outcome. We conducted a sec-
ond prospective study in mechanically
ventilated infants and children to validate
the relative risk of extubation failure that
we observed in our previous study. We
hypothesized that the relative risk of ex-
tubation failure and the threshold values
for low and high risk of extubation failure

Crit Care Med 2000 Vol. 28, No. 8 2991

would be similar to our first study despite
the change in clinical practice of wean-
ing.
MATERIALS AND METHODS
This study was approved by the hospital
institutional review board, and the need for
informed consent was waived. All infants and
children admitted to the Pediatric Intensive
Care and the Neonatal Intensive Care Units of
the Children’s Hospital of Pittsburgh from
July 1994 to June 1996 who required mechan-
ical ventilation for ⱖ24 hrs were eligible for
the study. All patients were weaned using syn-
chronized intermittent mandatory ventilation,
assisted mechanical ventilation using pressure
support, or a combination of synchronized
intermittent mandatory ventilation with pres-
sure support. Synchronized intermittent man-
datory ventilation breaths were volume regu-
lated and time cycled ventilation with no
control or limitation of peak ventilatory in-
spiratory pressure (PIP). The decision to extu-
bate was made by the primary physician and
was based primarily on clinical examination,
blood gases, and available ventilatory parame-
ters. Some patients were weaned off all venti-
lator support before extubation, whereas some
were extubated from a low level of ventilator
support. The primary physician was responsi-
ble for the weaning process and was blinded to
the results of the study. The decision to rein-
tubate also was made by the primary physician
and was based on clinical examination, blood
gases, or both. The aspects of clinical exam
that were used to assess readiness to extubate
included respiratory rate, air entry, and a clin-
ical judgment about the work of breathing.
Extubation failure was defined as the require-
ment for reintubation within 48 hrs of extu-
bation. Patients with neuromuscular disease,
neonates ⬍ 37 wks of gestational age, and
those who were reintubated for upper airway
obstruction were excluded from the study.
Data Collection. Data collected included
age, weight, gender, admitting diagnosis, and
duration of intubation. All measurements
were made immediately before extubation.
Ventilator rate, PIP, mean airway pressure
(Paw), and FIO2 before extubation were re-
corded. The level of positive end-expiratory
pressure or continuous positive airway pres-
sure also was recorded. Tidal volume delivered
by the ventilator to the patient was measured
at the hub of the endotracheal tube (ETT) by a
pneumotachograph and was standardized to
body weight. While the patient was still on the
ventilator, variables recorded were heart rate,
respiratory rate, blood pressure, and blood
gases. We also noted the presence or absence
of retractions and paradoxic breathing before
extubation. The ventilator was disconnected
from the ETT and attached to a Mapleson bag
with supplemental oxygen. The flow rate was
2992
adjusted so as not to produce any positive Table 1. Threshold values for a low (ⱕ10%) and
pressure in the airway. Once the breathing was a high (ⱖ25%) failure
stable off the ventilator, inspiratory pressure
(Pi), inspiratory time (Ti), total respiratory Low-Risk High-Risk
cycle time, and the respiratory rate of sponta- Value Value
neous breathing were measured from the Variable (ⱕ10%) (ⱖ25%)
pressure-time tracings obtained from a cathe-
ter with the tip at the end of the ETT by using VTspont (mL/kg) ⱖ6.5 ⱕ3.5
a Ventrak respiratory monitor (Novametrix, FIO2 ⱕ0.30 ⬎0.40
Paw (cm H2O) ⬍5 ⬎8.5
Wallingford, CT). Tidal volume of a spontane-
OI ⱕ1.4 ⬎4.5
ous breath was measured at the hub of the FrVe (%) ⱕ20 ⱖ30
ETT by using a pneumotachograph and was PIP (cm H2O) ⱕ25 ⱖ30
indexed to body weight. The maximum nega- Cdyn (mL/kg/cm H2O) ⱖ0.9 ⬍0.4
tive inspiratory pressure (Pimax) for a sponta- Vt/Ti (mL/kg/sec) ⱖ14 ⱕ8
neous breath was measured as described by
Marini et al. (18). VTspont, spontaneous tidal volume indexed to
Indices that incorporated more than one body weight; FIO2, fraction of inspired oxygen;
measure of respiratory function were the ratio Paw, mean airway pressure; OI, oxygenation in-
of Pi to Pimax (Pi/Pimax), oxygenation index dex; FrVe, fraction of total minute ventilation
(OI), dynamic compliance of the respiratory provided by the ventilator; PIP, peak ventilatory
system, the fraction of the total minute venti- inspiratory pressure; Cdyn, dynamic compliance;
lation that was provided by the ventilator ex- Vt/Ti, mean inspiratory flow.
pressed as a percentage (FrVe), mean inspira- SI unit conversion: 1 cm H2O ⫽ 0.098 kPa.
tory flow, frequency to tidal volume ratio (f/
VT), and CROP (compliance, rate, oxygenation,
and pressure). These indices were calculated Table 2. Clinical characteristics of patients
as previously described (5). Postextubation
data consisted of whether reintubation oc- Prediction Validation
curred within 48 hrs and the reason for rein- Group Group
tubation. Factor (n ⫽ 208) (n ⫽ 312)
Data Analysis. The extubation failure rate
was calculated for each variable and index of Age, yrs (%)
⬍1 50.5 50
respiratory function. Failure rates are ex-
1–5 24 25
pressed as percentages with 95% confidence ⬎5 25.5 25
intervals (19). To determine whether there Duration of intubation,
was a linear trend in extubation failure rate as days (%)
each variable or index increased or decreased, ⬍3 39.9 38.5
we performed a regression test for a linear 3–7 37.5 37.5
trend in proportions with preselected ranges 7–14 16.8 18.3
and the corresponding failure rates (19). The ⬎14 5.8 5.8
ranges for each variable and index were se- Male:Female 81:127 120:192
lected a priori, as described previously (5). A Z Extubation failure (%) 16.3 16.0
statistic of ⱖ1.96 corresponding to p ⱕ .05
was considered statistically significant (19). In
our previous study, we were able to identify
cutoff values for selected variables that defined in Table 3. Preextubation data were also
a low risk or a high risk of extubation failure similar between the two groups, as shown
(5). Low risk was defined as a failure rate ⱕ in Table 4. The Z scores and the p for the
10% and a high risk of failure was defined as a test for linear trend in proportions are
failure rate ⱖ 25%; the cutoff values are
shown in Table 5. There were no differ-
shown in Table 1. We compared the failure
rates from this study (validation group) with
ences between the prediction and the val-
those published previously (prediction group) idation groups. There were no differences
by using the chi-square test for proportions. in the failure rates for any of the cutoff
We analyzed the distribution of categorical values for PIP, Paw, FIO2, OI, dynamic
variables between groups by using the chi- compliance, spontaneous tidal volume,
square test or the Fisher’s exact test, with p ⬍ FrVe, and mean inspiratory flow (Vt/Ti)
.05 considered significant. (Figs. 1 and 2).
RESULTS DISCUSSION
We enrolled 312 patients in the study. Discontinuation of mechanical venti-
There were no differences in any of the lation will be successful if the patient has
clinical characteristics between the pre- the capacity to sustain spontaneous
diction and validation groups (Table 2). breathing without undue effort, if the pa-
The reasons for reintubation were similar tient has a normal inspiratory drive, and
in both groups, and the results are given if the patient does not have an increased
Crit Care Med 2000 Vol. 28, No. 8
Table 3. Reasons for reintubation

T
Prediction Validation his study validates
Group Group
(%) (%) our previous study
(n ⫽ 34) (n ⫽ 50) Z Statistic p Value
showing that pre-
Poor effort (apnea/decreased air entry) 24 22 ⫺0.03 .98
Excessive effort (severe retractions and tachypnea) 42 40 ⫺0.01 .99 extubation variables easily
Neurologic (absent airway reflexes) 6 2 0.39 .70
Cardiovascular insufficiency 9 12 0.06 .95 obtained at the bedside can
Inadequate oxygenation (PaO2/FIO2, ⬍100) 9 12 0.06 .95
Respiratory acidosis (PaCO2, ⬎60 torr, with pH ⬍7.30 9 12 0.06 .95 predict the relative risk of
There were no significant differences between the two groups. The two groups were compared by reintubation.
the chi-square test for proportions. To convert torr to kPa, multiply values by 0.133.

Table 4. Pre-extubation data

higher when patients are extubated from
Successfully Failed
a high level of ventilator support as
Variable Extubated Extubation p Value
shown by a higher FIO2, Paw, OI, and
Age (months) 37.6 ⫾ 5.2 52.8 ⫾ 12.1 .14 FrVe, suggesting that the patient’s ability
pH 7.41 ⫾ 0.01 7.39 ⫾ 0.01 .38 to sustain spontaneous breathing after
PaO2 (torr) 100.3 ⫾ 5.3 101.8 ⫾ 5.8 .6 extubation was overestimated. Con-
PaCO2 (torr) 39.5 ⫾ 0.6 41.3 ⫾ 1.4 .23 versely, a spontaneous tidal volume that
HCO⫺ 3 (mmol/L) 27.4 ⫾ 0.3 26.5 ⫾ 0.8 .9
BE (mmol/L) 2.4 ⫾ 0.4 2.5 ⫾ 0.7 .9
is at least normal, a low FIO2, a low Paw,
Duration of intubation (days) 5.0 ⫾ 0.4 5.2 ⫾ 0.6 .8 a low OI, a low PIP, a high dynamic
Ventilator rate (breaths/min) 4.7 ⫾ 0.2 4.4 ⫾ 0.3 .4 compliance, a low FrVe, and a normal or
high Vt/Ti are associated with a low risk
HCO⫺3 , bicarbonate; BE, base deficit/excess. of failure. As in our previous study, we did
Data presented as mean ⫾ SEM. The groups were compared by unpaired t-test. To convert torr to not find Pi, Pimax, or Pi/Pimax to be useful
kPa, multiply values by 0.1333.
predictors of extubation outcome. The
Table 5. Results of the regression test for a linear trend in proportions
relative risk of extubation failure and the
threshold values for low and high risk
Prediction Group Validation Group were not different from our previous
study. Not only did the patients in our
Variable Z Statistic p Value Z Statistic p Value study vary in age, diagnoses, duration of
intubation, and the use of neuromuscular
RRstd 0.29 .768 0.32 .7
blockade, but there was considerable
Pi 0.82 .412 0.8 .45
Pimax 0.62 .536 0.65 .5 variation among physicians’ judgments
Pi/Pimax 0.27 .791 0.32 .7 concerning the readiness for extubation,
VTspont 2.6 .01 2.63 .011 and there was a change in clinical prac-
FIO2 2.35 .018 2.5 .01 tice since our first study. We did not
Paw 2.51 .012 2.5 .01
OI 2.53 .012 2.5 .01 examine the impact of these factors on
FrVe 3.149 .002 3.2 .002 the predictive capacity of these variables.
PIP 3.7 ⬍.001 3.65 ⬍.001 A much larger study would be needed to
Cdyn 1.57 .116 1.54 .11 examine the independent effects of these
Vt/Ti 2.86 .004 2.9 .004
factors in predicting extubation success
f/Vt 0.96 .34 1 .38
CROP index 0.83 .41 0.8 .4 and failure. Despite these confounding
factors, our study shows that the esti-
RRstd, respiratory rate standardized to age; Pi, spontaneous inspiratory pressure; Pimax, maximum mated risk of extubation indicated by the
negative inspiratory pressure of a spontaneous breath; VTspont, spontaneous tidal volume indexed to measures of respiratory function is ro-
body weight; Paw, mean airway pressure; OI, oxygenation index; FrVe, fraction of total minute bust and objective. The variables exam-
ventilation provided by the ventilator; PIP, peak ventilatory inspiratory pressure; Cdyn, dynamic ined in our study can be measured easily
compliance; Vt/Ti, mean inspiratory flow; f/Vt, respiratory rate to tidal volume ratio indexed to body
and quickly at the bedside with simple
weight; CROP index, dynamic compliance, respiratory rate, oxygenation, and maximum negative
instruments present in most intensive
inspiratory pressure.
care units.
Adult studies indicate that not all pa-
load on the respiratory muscles. This tidal volume, there is an increased load tients need a gradual reduction of me-
study confirms our previous observation on the respiratory muscles as indicated chanical ventilation (22–24). These stud-
that in mechanically ventilated infants by a high PIP or a low dynamic compli- ies on weaning were conducted only on
and children, there is a higher risk of ance, or there is decreased central in- patients who failed an initial trial of spon-
failure when the effort of breathing re- spiratory drive as shown by a low Vt/Ti taneous breathing without extubation
sults in a lower than normal spontaneous (5). Additionally, the risk of failure is (22–24). If the patients failed this trial,

Crit Care Med 2000 Vol. 28, No. 8 2993

Figure 1. Top left, comparison of low and high risk of extubation failure for spontaneous tidal volume (VTspont). Top right, comparison of low and high risk
of extubation failure for fraction of inspired oxygen (FIO2). Bottom left, comparison of low and high risk of extubation failure for mean airway pressure
(Paw). Bottom right, comparison of low and high risk of extubation failure for oxygenation index (OI).
they were then subjected to a weaning
protocol. There are no studies on wean-
ing protocols in children. Currently, de-
termining the optimal time for extuba-
tion is based on a clinical evaluation of
the patient’s ability to sustain spontane-
ous breathing when mechanical ventila-
tion is discontinued. Ideally, a child’s
ability to sustain spontaneous breathing
should be tested without any ventilator
support. The current practice of extuba-
tion generally follows a period of weaning
to what the clinician considers a low level
of ventilator support. There is a general
reluctance to evaluate mechanically ven-
tilated infants and young children on
continuous positive airway pressure, be-
cause of the concern that the endotra-
cheal tube and the ventilator circuit im-
pose an undue burden on the respiratory
muscles. Therefore, it is not uncommon
for infants and children to be extubated
from a low ventilator rate of 4 –5 breaths/
min. More recently, it has become a com-
mon practice to apply a low level of pres-
sure support, designed to overcome the
respiratory system resistance. If the ven-
tilator breaths are large, especially when
coupled with a low spontaneous tidal vol-
ume, the ventilator may provide a sub-
stantial fraction of the total minute ven-
tilation and may mask the patient’s
2994
ability to sustain spontaneous breathing
after extubation. The observation that a
high preextubation FrVe can be associ-
ated with a higher extubation failure rate
is supported by studies in neonates and
adults (4, 12) and suggests a need to
evaluate the patient’s ability to breathe
spontaneously at a lower level of support.
Similar to the adult experience, it should
be possible for many children to be extu-
bated with minimal or no weaning by
using the threshold values from this
study. Any patient with a low risk of fail-
ure based on the threshold values shown
in Table 1 can be extubated immediately.
If a patient has a high risk of failure as
judged by the threshold values given in
Table 1, one must determine its reason.
All patients must have a normal inspira-
tory drive, and if it is low, oversedation
should be suspected and corrected. If the
reason for the high risk of failure is inef-
fective spontaneous efforts, as suggested
by spontaneous tidal volume ⱕ 3.5 mL/
kg, it might be prudent to continue me-
chanical ventilation until the spontane-
ous tidal volume improves. An increased
load on the respiratory muscles (a high
PIP and a low dynamic compliance) also
may indicate continuing mechanical ven-
tilation. This approach may avoid both
unnecessary prolongation of ventilation
and premature extubation, both of which
can increase morbidity and health care
costs. The threshold values also may be
applied in any prospective study of wean-
ing protocols. The time required to reach
a certain threshold would be a useful and
objective outcome measure to compare
weaning protocols.
Our observation that a low spontane-
ous tidal volume is associated with a high
risk of extubation failure is similar to that
reported in adults (1, 11). This suggests
that it may not be so much the effort of
breathing but rather the outcome of that
effort that determines the ability to sus-
tain spontaneous breathing. A low dy-
namic compliance or a high airway resis-
tance, reflecting an increased imposed
load on the respiratory muscles, in-
creases PIP with volume-regulated time-
cycled ventilation and is associated with
extubation failure in neonates (3, 20, 21).
This observation is similar to that seen in
our study. A low inspiratory drive can
result in hypoventilation after extuba-
tion. Adults who fail extubation do not
have a decreased Vt/Ti but have rapid
shallow breathing with an increase in
Vt/Ti (1). This is caused by a more pro-
nounced decrease in Ti compared with
the decrease in spontaneous tidal volume
(1). Our study shows that when the Vt/Ti
Crit Care Med 2000 Vol. 28, No. 8
Figure 2. Top left, comparison of low and high risk of extubation failure for fraction of total minute ventilation provided by the ventilator (FrVe). Top right,
comparison of low and high risk of extubation failure for peak ventilatory inspiratory pressure (PIP). Bottom left, comparison of low and high risk of
extubation failure for dynamic compliance (Cdyn). Bottom right, comparison of low and high risk of extubation failure for mean inspiratory flow (Vt/Ti).
is low, the failure rate is high. Overseda-
tion is the primary reason for a low in-
spiratory drive in these patients. A second
possibility may be that because children
normally breathe at rapid rates, their
short Ti may be relatively fixed and thus
their failure may depend on a more pro-
nounced change in tidal volume. We do
not know what pattern of Vt/Ti would be
observed after extubation in patients who
are successfully extubated compared with
those who are reintubated. As in our pre-
vious study, the f/VT ratio and CROP were
not useful in predicting extubation fail-
ure in children. Because there was a wide
range of age groups with different respi-
ratory rates, f/VT ratio and CROP may not
be appropriate as predictors of extubation
success or failure in the pediatric popu-
lation. Whether age-specific f/VT or CROP
is useful is currently unknown.
In summary, this study validates our
previous study showing that preextuba-
tion variables easily obtained at the bed-
side can predict the relative risk of rein-
tubation. Based on these results, we
conclude that infants and children fail
extubation because of poor effort (a de-
creased spontaneous tidal volume), in-
creased load on the respiratory muscles
(a high PIP and a low dynamic compli-
Crit Care Med 2000 Vol. 28, No. 8
ance), or a decreased inspiratory drive
(decreased Vt/Ti). Additionally, an in-
creased preextubation level of ventilator
support (a high Paw, OI, or FrVe) is as-
sociated with increased failure rates.
Therefore, criteria for extubation must
account for the relative risk of reintuba-
tion. A multicenter study currently is be-
ing undertaken to validate these predic-
tors in other centers. Finally, integrated
indices such as f/VT ratio and the CROP
index do not account for normal develop-
mental changes in respiratory function
including mechanics and gas exchange
and, therefore, are poor predictors of ex-
tubation success and failure in infants
and children.
ACKNOWLEDGMENTS
We acknowledge and thank the all the
respiratory care practitioners in all inten-
sive care units at Children’s Hospital of
Pittsburgh for their help in the meticu-
lous data collection required in this
study. We also acknowledge and thank
Richard Orr, MD, and Joseph Carcillo,
MD, from the Department of Anesthesi-
ology/CCM, University of Pittsburgh, for
their valuable suggestions and assistance.
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2996 Crit Care Med 2000 Vol. 28, No. 8