Randolph AG, Wypij D, Venkataraman ST, Hanson JH, Gedeit RG, Meert KL, Luckett PM, Forbes P, Lilley M, Thompson J, Cheifetz IM, Hibberd P, Wetzel R, Cox PN, Arnold JH, for the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI)
Network . Effect of Mechanical Ventilator Weaning Protocols on Respiratory Outcomes in Infants and ChildrenA Randomized Controlled Trial. JAMA. 2002;288(20):2561–2568. doi:10.1001/jama.288.20.2561
Author Affiliations: Children's Hospital, Boston, Mass (Drs Randolph, Wypij, Hibberd, and Arnold, Ms Lilley, and Mssrs Forbes and Thompson); Harvard Medical School (Drs Randolph and Arnold) and Harvard School of Public Health (Dr Wypij), Boston; Children's Hospital of Pittsburgh, Pittsburgh, Pa (Dr Venkataraman); Children's Hospital Oakland, Oakland, Calif (Dr Hanson); Children's Hospital of Wisconsin, Milwaukee (Dr Gedeit); Children's Hospital of Michigan, Detroit (Dr Meert); Children's Medical Center of Dallas, Dallas, Tex (Dr Luckett); Duke Children's Hospital, Durham, NC (Dr Cheifetz); Children's Hospital Los Angeles, Los Angeles, Calif (Dr Wetzel); The Hospital for Sick Children, Toronto, Ontario (Dr Cox).
Caring for the Critically Ill Patient Section Editor: Deborah J. Cook, MD, Consulting Editor, JAMA.
Context Ventilator management protocols shorten the time required to wean adult
patients from mechanical ventilation. The efficacy of such weaning protocols
among children has not been studied.
Objective To evaluate whether weaning protocols are superior to standard care
(no defined protocol) for infants and children with acute illnesses requiring
mechanical ventilator support and whether a volume support weaning protocol
using continuous automated adjustment of pressure support by the ventilator
(ie, VSV) is superior to manual adjustment of pressure support by clinicians
Design and Setting Randomized controlled trial conducted in the pediatric intensive care
units of 10 children's hospitals across North America from November 1999 through
Patients One hundred eighty-two spontaneously breathing children (<18 years
old) who had been receiving ventilator support for more than 24 hours and
who failed a test for extubation readiness on minimal pressure support.
Interventions Patients were randomized to a PSV protocol (n = 62), VSV protocol (n
= 60), or no protocol (n = 60).
Main Outcome Measures Duration of weaning time (from randomization to successful extubation);
extubation failure (any invasive or noninvasive ventilator support within
48 hours of extubation).
Results Extubation failure rates were not significantly different for PSV (15%),
VSV (24%), and no protocol (17%) (P = .44). Among
weaning successes, median duration of weaning was not significantly different
for PSV (1.6 days), VSV (1.8 days), and no protocol (2.0 days) (P = .75). Male children more frequently failed extubation (odds ratio,
7.86; 95% confidence interval, 2.36-26.2; P<.001).
Increased sedative use in the first 24 hours of weaning predicted extubation
failure (P = .04) and, among extubation successes,
duration of weaning (P<.001).
Conclusions In contrast with adult patients, the majority of children are weaned
from mechanical ventilator support in 2 days or less. Weaning protocols did
not significantly shorten this brief duration of weaning.
Acute respiratory, cardiac, and neurologic failure in infants and children
lead to intubation, mechanical ventilator support, and pharmacological sedation.
Despite the frequent use of mechanical ventilation, methods for weaning children
from respiratory support have never been rigorously studied.1 Weaning
methods are extrapolated from studies in adult patients and prematurely born
neonates. Extrapolation to infants and children may not be appropriate due
to the unique aspects of their pulmonary physiology, respiratory mechanics,2 and epidemiology of acute lung injury. Discontinuing
mechanical ventilation as soon as it is no longer needed is important to prevent
respiratory complications3 and physiological
dependence on the sedative and narcotic drugs required to keep ventilated
children comfortable and safe.4
Studies in adult patients have shown that, compared with care guided
by the individual practices of clinicians, use of protocols to guide the weaning
of patients from mechanical ventilator support leads to improved patient outcomes.5,6 Pressure support ventilation (PSV)
and volume support ventilation (VSV) are modes commonly used to wean children
from mechanical ventilator support. The 2 modes are similar in that they are
both patient-triggered spontaneous breathing modes that use pressure support.
Using PSV, clinicians intermittently adjust the level of pressure support
to achieve acceptable respiratory parameters7 with
gradual weaning to a minimal amount of PSV.8 Volume-support
ventilation is an automated mode where the amount of pressure support is continually
adjusted by the ventilator to achieve a minimum minute ventilation goal.9 Because accepted protocols for applying these modes
in children do not currently exist, there is great variability in clinical
The primary goals of this study were to evaluate whether weaning protocols
are superior to standard care (no defined protocol) for infants and children
with acute illnesses requiring mechanical ventilator support and whether a
weaning protocol using continuous automated adjustment of pressure support
by the ventilator (ie, VSV) is superior to manual adjustment of pressure support
by clinicians (ie, PSV). The secondary goals of the study were to evaluate
the performance of a set of extubation criteria on extubation success and
failure and to study the relationship between sedative use during weaning
and respiratory outcomes.
The Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
is a consortium of investigators at pediatric intensive care units (ICUs)
across North America. Eligible children admitted between November 1999 and
April 2001 in ICUs at 10 children's hospitals were enrolled. Children were
eligible for the study if they required ventilator support for more than 24
hours. The study was approved by the institutional review board at each hospital.
Consent was obtained from at least one parent or legal guardian before enrollment.
Exclusion criteria were: age 18 years or older, corrected gestational
age less than 38 weeks, diaphragmatic hernia or paralysis, ventilator use
prior to admission when the patient was at baseline health status (including
use of noninvasive ventilator support), cyanotic congenital heart disease
with unrepaired or palliated right-to-left intracardiac shunt, history of
single ventricle defect at any stage of repair, significantly diminished lung
capacity (estimated resting tidal volume <6 mL/kg), decreased lung vascularity,
anatomical obstruction of lower airways, primary pulmonary hypertension or
anticipated need for nitric oxide after extubation, previous bone marrow or
lung transplant, spinal cord injury above the lumbar region, tracheal or upper
airway obstructive conditions, status asthmaticus in children 2 years or older,
and progressive neuromuscular weakness. Children currently enrolled in another
trial in which the intervention potentially influenced a patient's respiratory
outcome were excluded. Children were also excluded if a decision to withdraw
or limit life support was in place.
Data were collected prospectively. Pediatric Risk of Mortality III (PRISM
III) scoring was performed in all patients during the first 24 hours of admission
to assess illness severity.10
Mechanically ventilated patients in the pediatric ICUs were prospectively
evaluated and screened daily to test for extubation readiness. Eligibility
criteria for testing were: spontaneous respiratory effort; gag or cough with
suctioning; pH of 7.32 to 7.47 on most recent blood gas analysis; positive
end-expiratory pressure (PEEP) of 7 cm H2O or lower and fraction
of inspired oxygen (FIo2) of 0.6 or less; level of consciousness
acceptable for extubation; attending physician's approval; no clinical need
for increased ventilator support in the last 24 hours; no planned operative
procedures requiring heavy sedation in the next 12 hours; and no excessive
leak around the endotracheal tube (ETT) requiring ventilator manipulations.
Enteral feeding was stopped for testing.
The extubation readiness test (ERT) consisted of changing the FIO2 to 0.5 (left at current setting if already <0.5 with saturation
by pulse oximetry [SpO2] reading ≥95%) and decreasing the PEEP
to 5 cm H2O (left at current setting if already <5 cm H2O with SpO2 reading ≥95%). Patients unable to maintain
SpO2 of 95% or higher failed the test; those who maintained SpO2 of 95% or higher had their ventilator mode changed to PSV and were
placed on minimal PSV. Minimal pressure support was adjusted for the ETT size
because of increasing resistance with lower ETT size11 (ETT
size 3.0-3.5 = pressure support of 10 cm H2O; ETT size 4.0-4.5
= pressure support of 8 cm H2O; ETT size ≥ 5.0 = pressure support
of 6 cm H2O). Exhaled tidal volumes were measured at the ETT using
a CO2SMO Plus monitor (Novametrix Medical Systems Inc, Wallingford,
Conn) with neonatal, pediatric, or adult sensors. Patients were monitored
during the test for 2 hours.
Patients were classified as failing the test if at any time in the 2-hour
period their SpO2 was less than 95%, their exhaled tidal volume
was less than 5 mL/kg ideal body weight, or their respiratory rate was outside
of the acceptable range for their age (for age <6 months, 20-60/min; 6
months-2 years, 15-45/min; 2-5 years, 15-40/min; >5 years, 10-35/min). Ideal
body weight was estimated as the 50th percentile for age and sex from National
Center for Health Statistics growth charts12 and
was the weight used for adjustment of all respiratory parameters during the
test and within the protocol groups of the study. As soon as any criteria
for failure were met, the patient was removed from the test, placed back on
previous ventilator settings, and randomized to PSV, VSV, or no protocol.
Randomization was performed using a permuted blocks design, stratified
by ICU, with random block sizes of 3, 6, or 9. Packets were placed in opaque
envelopes with a second paper barrier and signed over the unbroken seal to
ensure that the assignment was concealed.
Ventilator management prior to weaning was at the discretion of the
physician. During weaning, all patients were placed on a Servo 300 ventilator
(Siemens-Elema, Solna, Sweden). Children were evaluated for 48 hours after
they were extubated, and the time of extubation was recorded as the primary
In the no protocol group, weaning was at the discretion of the physician
and no management recommendations were made. Ventilator management followed
the protocols determined for the PSV and VSV groups. Both protocols used the
CO2SMO Plus monitor attached to a neonatal, pediatric, or adult
sensor at the ETT for all measurements of exhaled tidal volume. The patient's
physician was responsible for implementing the ventilator weaning protocols,
obtaining blood gas tests when clinically indicated, and deciding when temporary
cessation of the protocol was required for procedures or due to clinical deterioration.
Physicians were encouraged to evaluate sedation and analgesia if the patient's
respiratory rate was outside of the goal for age.
For both protocols, FIO2 and PEEP were adjusted to maintain
SpO2 at 95% or higher using the following recommended methods:
decrease PEEP by 1 cm H2O every 4 hours if the SpO2 is
95% or higher with FIO2 less than or equal to 0.6, weaning FIO2 to 0.5 or less once PEEP is 5 cm H2O or lower; and, if
SpO2 is lower than 95% at any time, increasing FIO2 by
10% and increasing PEEP if necessary. The PSV and VSV protocols were developed
at 1 site, refined during a 2-day consensus meeting of all investigators,
tested on 10 patients, then pretested at each site by randomizing 2 patients
to each protocol. Data on protocol compliance were monitored using a specially
designed time-sensitive form and protocol deviation forms. Patients in the
protocol groups had to pass the ERT prior to extubation.
In the PSV protocol, the amount of pressure support was adjusted to
achieve an exhaled tidal volume goal of 5 to 7 mL/kg. Instructions for weaning
were: (1) Every 4 hours, decrease the pressure support by 2-cm H2O
increments if the patient maintains tidal volume within the goal range and
decrease pressure support earlier if tidal volumes are consistently over 7
mL/kg. If tidal volumes are consistently less than 5 mL/kg, increase pressure
support by 2-cm H2O increments to achieve the tidal volume goal.
(2) Perform an ERT once pressure support is decreased to 16 cm H2O
and patient tolerates this level for 2 hours with an SpO2 of 95%
or higher (with PEEP ≤5 cm H2O and FIO2 ≤0.5)
and a respiratory rate within goal range for age. (3) If the child fails the
ERT, return to the previous pressure support setting, hold for 4 hours, then
decrease the pressure support stepwise by 2-cm H2O increments every
4 hours until the level used in the ERT is reached.
In the VSV protocol, the ventilator in volume support mode automatically
adjusted the level of pressure support to achieve an exhaled tidal volume
of 5 to 7 mL/kg. Instructions for weaning were: (1) Adjust initial set inspired
tidal volume to achieve exhaled tidal volume of 6 mL/kg (measured at the ETT)
and set backup respiratory rate according to age (for age <6 months, 16/min;
6 months-2 years, 14/min; 2-5 years, 12/min; >5 years, 10/min). (2) Monitor
tidal volumes at the ETT for the first 30 minutes and every 12 hours to ensure
that they remain between 5 to 7 mL/kg. (3) Perform an ERT (maximum of 2 tests
in 24 hours) when peak inspiratory pressure is 20 cm H2O or lower,
SpO2 is 95% or higher (on PEEP ≤5 cm H2O and FIO2 ≤0.5), and respiratory rate is within the goal for age.
Many children received multiple sedative drugs and some received intermittent
paralytic agents for procedures. All sedative use was recorded prospectively.
The amount of sedation given in the first 24 hours of weaning was calculated
using a score for which 1 point was given for the amount of each drug that
would be equivalent to 1 hour of sedation in a nontolerant subject. The relative
potency scale for opiates and benzodiazepines used by Wilson et al13 was modified for children with the help of the pediatric
pharmacology staff at Children's Hospital, Boston, Mass. All opiates were
converted to morphine equivalents using the following conversions to equal
1 mg of morphine sulfate: 15 µg fentanyl citrate, 0.15 mg hydromorphone
hydrochloride, 0.3 mg methadone hydrochloride, 20 mg codeine. All benzodiazepines
were converted to midazolam equivalents using the following conversions to
equal 1 mg of midazolam: 2 mg diazepam, 0.33 mg lorazepam. For the sedation
scoring, 1 point was given for each of the following: morphine or midazolam
equivalents of 0.1 mg/kg, pentobarbital 2 mg/kg, chloral hydrate 50 mg/kg,
any propofol use, any phenobarbitol use. Use of any antihistamines received
a point score of 0.5. For example, a child weighing 5 kg who, during the first
24 hours of weaning, received a total of 4 mg of morphine sulfate, 3 mg of
lorazepam (converted to 9 mg midazolam), and a 30-minute infusion of propofol
for a procedure would have a sedative use score of 27 (ie, 8 + 18 + 1).
Our first hypothesis was that the time to successful extubation for
children receiving protocol-directed weaning (PSV and VSV combined) was equivalent
to or less than those receiving traditional physician-directed weaning (no
protocol). Decreasing the time to extubation from 4 days (based on data from
a pilot study) to 2.65 days (33% less) was considered clinically important.
Using a hazard ratio of 0.67, a 2-sided α of .05, and a 2:1 ratio of
children randomized to protocol-directed weaning vs physician-directed weaning,
a total of 306 weaning times (204 in the protocol-directed weaning group and
102 in the traditional weaning group) were required for 80% power.
Our second hypothesis was that the time to successful extubation for
children randomized to the VSV protocol was less than for those randomized
to the PSV protocol, because in VSV the pressure support level was continually
adjusted as the patient improved. Decreasing the median time to extubation
from 3 days to 2 days (33% less) was considered clinically important. Using
a hazard ratio of 0.67, a 2-sided α of .05, and a 1:1 ratio of children
randomized to PSV and VSV, a total of 328 weaning times (164 in each group)
were required for 80% power.
A priori, clinicians determined that a clinically important difference
between trial groups was a minimum of 1 day. An interim analysis was scheduled
at 306 patients. At this point, the data and safety monitoring board (DSMB)
was instructed to recommend ceasing enrollment in the no protocol group if
care provided using a protocol was proven equivalent to or better than care
provided without a protocol. They were also instructed to recommend increaseing
the sample size if necessary but to stop the study for lack of efficacy if
the differences in weaning times between study groups were unlikely to exceed
The study was analyzed on an intention-to-treat basis. The primary efficacy
variables were weaning success and, among the subset of patients who were
weaning successes, the duration of time to weaning. Weaning failure was defined
as either the reinstitution of mechanical ventilator support within 48 hours
of extubation (through an ETT or noninvasively) or failure to wean within
28 days of randomization. All patients were prospectively evaluated to hospital
discharge or transfer to another institution. Patients who died or were transferred
before completing the study were treated as weaning failures.
The Fisher exact test was used to compare the proportion of weaning
failures between groups. Logistic regression was used to assess the effects
on weaning of sedation received during the first 24 hours, after controlling
for study site, age, race, sex, PRISM III score, and days intubated prior
to randomization. Age groups were defined as neonate (younger than 30 days),
infant (younger than 1 year), child (younger than 12 years), and adolescent
(younger than 18 years). Quartiles were used to define levels for sedation
score and days intubated prior to randomization.
Weaning-time analyses considered only cases that were successfully extubated.14,15 Kaplan-Meier survival curves and
log-rank tests were used to compare the weaning times of the groups. Proportional
hazards regression was used to assess the effects of covariates on weaning
times. SAS v8.0 (SAS Institute Inc, Cary, NC) was used for all analyses.
Enrollment in the trial began at the first site in November 1999. The
first interim analysis was performed in February 2001, after 105 patients
were randomized. The second interim analysis was performed after 182 patients
were randomized. On April 30, 2001, the DSMB stopped the trial due to lack
A total of 313 eligible patients underwent the ERT. Of these, 182 (58%)
failed the test and were randomized (Figure
1). Reasons for failing the test were related to exhaled tidal volume
in 52 children (28.6%), to SpO2 in 10 (5.5%), to respiratory rate
in 32 (17.6%), and to more than 1 criterion in 88 (48.4%). Of the 131 patients
(42%) passing the test, 115 (88%) were extubated within 24 hours. Of these,
97 (84%) were successfully extubated, 15 (13%) were reintubated, and 3 (3%)
required use of noninvasive ventilator support.
Of the 182 children randomized in the study, 62 were randomized to the
PSV protocol, 60 to the VSV protocol, and 60 to no protocol or standard care
(Figure 1). The number of children
enrolled at each center ranged from 4 to 31. One child was excluded from the
analysis after randomization (to the VSV protocol) because social services
determined that the foster mother was not eligible to give consent for a study.
Two ineligible patients were randomized: a 20-year old with trisomy 21 (to
no protocol) and an infant with repaired congenital diaphragmatic hernia (to
the PSV protocol). Both were analyzed as extubation failures. The tables do
not include the 1 patient excluded after randomization or the 2 ineligible
patients, and report the results of the other 179 patients. Further analyses
were performed including the 2 ineligible patients' data, and the results
are reported in the text.
Baseline variables did not differ by treatment group with regard to
history of chronic illness, admission diagnosis, age, sex, or length of time
receiving ventilation prior to randomization (Table 1). Neonates comprised 17.3% of the study population, with
87% of these originating from home and 13% transferred after birth for persistent
pulmonary hypertension of the newborn. Follow-up was complete for all subjects
except for 1 child in the VSV protocol who was transferred to another hospital.
This child was treated as an extubation failure. Four children died after
randomization but before hospital discharge (2 VSV, 2 PSV). All 4 had redirection
of care and withdrawal of support because of a change in prognosis due to
their underlying diseases.
Although the overall analysis was by intention to treat, we monitored
protocol compliance prospectively. The number of children completing the protocol
was 39 of 59 (66%) in the VSV group and 40 of 61 (66%) in the PSV group. One
child in the VSV group was transferred prior to extubation. Of the 12 children
whose extubations were unplanned (5 VSV, 5 PSV, 2 no protocol), none failed
extubation. Of the 16 children extubated by their physician before passing
the ERT (6 VSV, 10 PSV), 5 (31%) failed extubation (2 were reintubated and
3 received noninvasive ventilator support).
Two children were removed from the protocol at parental request (1 VSV,
1 PSV) but the attending physicians caring for these children reported acceptable
protocol performance. Twelve children (10%) were removed from the protocols
at physician request (7 VSV, 5 PSV). Four had persistent apneic episodes,
2 had excessive ETT leaks interfering with effective ventilation, 5 had respiratory
deterioration and the physicians elected not to reenter them in the protocol
when they were ready to wean again, and 1 died after redirection of care due
to poor prognosis.
Extubation was delayed more than 4 hours in 25 children (8 VSV, 17 PSV).
The reasons for these delays were clinical team not available (5), neurologic
status (5), apnea (4), no ETT leak (2), and other (9).
In the no protocol group, a total of 9 modes of ventilation available
on the ventilator were used at least once with single modes of ventilation
used in 32 patients (55.2%), 2 modes in 18 (31%), 3 modes in 7 (12.1%), and
4 modes in 1 patient. In 22% of patients, the ventilator mode was changed
3 or more times during weaning. Modes commonly used were pressure control
with pressure support (39 children,[67%]) and volume control with pressure
support (15 children [27%]). Pressure support ventilation was used as the
single mode of ventilation during weaning in only 5 children (8.5%), but was
the last mode used prior to extubation in 26 children (43.3%) with a mean
(SD) extubation pressure support level of 7.6 (2.1) cm H2O. Volume
support ventilation was used at least once in 5 children (8.5%) and in only
1 child as the single mode of ventilation during weaning and prior to extubation.
In the 27 (45.8%) patients extubated from a mode with a set ventilator rate,
the mean (SD) set respiratory rate at extubation was 5.7 (2.8) per minute.
Weaning failure rates are summarized in Table 2. All weaning failures were due to extubation failure, redirection
of care and death, or patient transfer. Recorded reasons for extubation failure
were: lower respiratory tract problems (54.2%), upper airway obstruction and
stridor (25%), apnea (8.3%), cardiovascular insufficiency (4.2%), and other
(8.3%). There were no significant differences in failure rates in the 3 groups
(P = .44). Inferences were unchanged when 2 randomized
but ineligible patients were included, or when comparing groups using logistic
regression adjusting for study site.
Using logistic regression, a child's sex was identified as a significant
predictor of extubation failure, with failure occurring more often in boys
3). Overall there were 33 failures, of which 29 (87%) occurred in
boys. For boys, the failure rates in the PSV, VSV, and no protocol groups
were 21%, 45%, and 19%, respectively. For girls, they were 5%, 0%, and 13%.
In addition to child's sex, sedation during the first 24 hours of weaning
also significantly predicted extubation failure (P =
.04; df = 3). Extubation failure rates for the lowest
to the highest sedation quartiles were 20%, 14%, 7%, and 32%, respectively;
children in the highest quartile for sedation had more extubation failures
than those in the middle quartiles (P<.03 for
each). Sedative use was measured for the first 24 hours of weaning but not
at the time of extubation. This may explain why the odds ratios for the sedation
use score quartiles do not suggest a linear relationship. Inferences were
unchanged when children who were removed from the protocol at physician or
parent request, and the 4 children who died, were excluded from the analysis.
The model was also unchanged when age was used as a continuous variable or
when the presence of a chronic pulmonary condition or a chronic neurologic
condition was added separately to the model (all were nonsignificant as independent
predictors). There was no significant interaction between age and sex.
For the 146 successfully weaned cases, we compared the weaning times
of treatment groups. The mean weaning times for the PSV, VSV, and the no protocol
groups were 3.3, 2.5, and 3.2 days, respectively. The medians were 1.6, 1.8,
and 2.0 days (Table 2). Weaning
times did not differ significantly between treatment groups (P = .75).
Using proportional hazards regression, sedation during the first 24
hours of weaning significantly predicted weaning times (P<.001; df = 3). Mean weaning times for
the lowest to highest sedation score quartiles were 1.5, 2.9, 2.8, and 5.2
days. Median weaning times for the lowest to highest sedation score quartiles
were 1.0, 1.9, 1.9, and 3.0 days (Figure 2). Inferences were unchanged when 10 successfully extubated patients
who did not complete their assigned protocol were excluded from the analysis.
Limiting the duration of airway intubation and mechanical ventilator
support to the shortest possible time is of utmost importance for reducing
risk of nosocomial infection, tracheal irritation and injury, and sedative
dependency. Shortening the duration of mechanical ventilator support should
also decrease ICU length of stay and associated costs. The prevalent philosophy
is that it is necessary to gradually wean children experiencing respiratory
failure from the mechanical ventilator to retrain their respiratory muscle
strength. The findings of our study, the largest study performed to date in
infants and children with acute respiratory failure, suggest that gradual
weaning may not be indicated for the majority of infants and children. More
than a third of the children whose physicians determined that they were ready
to begin the weaning process, in fact, already met bedside extubation readiness
criteria and most were successfully extubated within 24 hours. More than half
of the children not meeting these criteria were successfully extubated within
2 days. At the time that study enrollment was terminated, there was no difference
in weaning between the protocol and nonprotocol groups, and no clinically
important difference was likely to be seen if the study went to completion.
In contrast to previous studies in adults that found that protocols shortened
duration of weaning,5,6 use of
weaning protocols had no impact on the duration of mechanical ventilator support
in this multicenter cohort of children.
Sedative use in the first 24 hours of weaning appears to strongly influence
both length of time on the ventilator and extubation failure in infants and
children. This is consistent with findings in adult patients.16 Cognitive
immaturity impedes the ability of children to be awake and tolerate having
an ETT in place. Although sedative drugs are required to prevent unplanned
extubation and associated adverse events, the need to maintain patient comfort
may impede liberation from the ventilator.
Another major finding of our study was that the great majority of extubation
failures were in male patients. The reasons for this are unclear. Male and
female patients were equally distributed across the various diagnostic and
age groups. Male sex has been associated with worse outcomes for neonatal
respiratory distress syndrome17 and for community-acquired
pneumonia in adult patients.18 Whether anatomical,
hormonal, or other influences underlie the difference in outcome is entirely
This is the only controlled trial to date evaluating methods of weaning
infants and children from mechanical ventilator support with extubation as
the study end point. Schultz et al19 randomized
223 children to a weaning protocol or to physician-directed weaning but used
the time at which minimum settings were achieved as the study end point. In
addition, patients were not placed on minimal settings prior to weaning to
ensure that they actually required weaning, and the median time in weaning
was 10 hours or less across groups. We believe that our study population is
representative of the majority of infants and children requiring mechanical
ventilation in pediatric ICUs for which a ventilator protocol would apply.
Ten large pediatric ICUs contributed patients to this study. Diagnoses that
could strongly influence ability to wean or successfully extubate, such as
upper airway obstruction or asthma, were excluded. The great majority of patients
were recovering from primary respiratory disease. In contrast to studies in
adult patients, we attempted to enroll patients in weaning as early as they
could tolerate spontaneous breathing. In adult studies, more than 75% of patients
passed the initial extubation readiness screening test and were not eligible
for entry,14,20 whereas in our
pediatric study only 42% passed this initial test. Despite this, the duration
of weaning was markedly shorter in these children compared with that reported
in the adult studies. It is possible that infants and children recover more
rapidly from a pulmonary insult. Less than 10% of the children in this study
had any chronic pulmonary disease, whereas in adult patients, chronic obstructive
pulmonary disease was present in more than 25% of patients enrolled in adult
weaning and extubation trials.14,15,21
Both protocol groups used objective criteria to determine extubation
readiness, in contrast to physician judgment in the no protocol group. Despite
this, objective criteria were no more predictive than physician judgment in
determining which children could be successfully extubated. The average extubation
failure rate was 19% using an ERT and 17% using physician judgment. These
failure rates are consistent with previous rates.22- 24 The
only potentially manipulable factor influencing failure rates was sedation
use. Because male sex was a strong determinant of extubation failure, more
stringent criteria for extubation readiness may be indicated for male patients.
We cannot rule out the possibility that ventilator weaning protocols
may be beneficial in the subgroup of children whose weaning time is longer
than 3 days. It is also possible, however, that daily testing15,21 and
daily interruption of sedative medications16 are
more effective in decreasing duration of mechanical ventilation. Like other
protocols for care, physician compliance with these protocols was not perfect;
however, many reasons for noncompliance were clinically justifiable. It is
possible that strict compliance with a multifaceted protocol used for a prolonged
period may not exceed 66% in the best circumstances. Given that the median
duration of weaning was short (2 days or less) in all arms of the study, it
is unlikely that improved protocol adherence would lead to a clinically important
difference in weaning times.
Our findings underscore the need for more effective methods of achieving
patient comfort without negative effects on ventilatory drive. Benzodiazepines
and narcotics are the main agents used and their use is associated with physiological
dependence and withdrawal in patients requiring them for 7 or more days.4,25 The long-term neurologic effects of
exposure to those agents on developing brains are unclear. We found that,
for the majority of infants and children receiving ventilator support for
acute respiratory failure, ventilator weaning protocols had no effect on duration
of mechanical ventilation. Improved management of sedative drugs and daily
testing for extubation readiness could potentially lead to shorter duration
of mechanical ventilator support.