Determinants
of Tracheobronchial
Histologic
Alterations
During
Conventional
Mechanical
Ventilation
LTC Thomas
E. Wiswell,
MC, USA,
LTC Barbara
S. Turner,
AN, USA,
MAJ
John A. Bley,
VC, USA,
MAJ
David
L. Fritz,
VC, USA,
and
MAJ Robert
E. Hunt,
VC, USA
From the Divisions of Medicine, Pathology, and Veterinary Medicine, Walter Reed Army Institute of Research; and the Nursing Research Service, Wafter Reed Army Medical Center, Washington, DC
ABSTRACT. It was hypothesized that diverse mecha-nisms may influence upper airway injury during
mechan-ical ventilation. To assess the roles of several factors in the propagation of such injury, the tracheobronchial his-tologic changes in 53 newborn piglets were compared following conventional positive pressure ventilation. Eight animals were assigned to each of four positive pressure ventilation groups at “low” settings (an FiO2 of 0.25, a frequency of 10 breaths per minute, a peak inspir-atory pressure of 20 cm H20, a positive end-expiratory pressure of 4 cm H20, a flow rate of 10 L/min, and an
inspiratory time to expiratory time ratio of 1:2): (1)
positive pressure ventilation with no hypotension or hy-poxemia; (2) positive pressure ventilation with hypoten-sion; (3) positive pressure ventilation with hypoxemia; and (4) positive pressure ventilation with both hypoten-sion and hypoxemia. In addition, eight piglets were as-signed to each of two positive pressure ventilation groups at “high” settings (greater frequency [40 breaths per minute], higher peak inspiratory pressure [40 cm and greater flow rate [17 L/min]): (1) positive pressure ventilation with no hypotension or hypoxemia; and (2) positive pressure ventilation with both hypotension and hypoxemia. The changes were mild and similar among the first three positive pressure groups at low settings. However, the injury scores of the combined hypotension and hypoxemia group (group 4) were greater than those of the former three positive pressure ventilation groups
(P < .004). The piglets receiving positive pressure venti-lation at high settings with no hypotension or hypoxemia (group 5) had no more injury than those in the first three groups receiving positive pressure ventilation. High
set-Received for publication Jul 1, 1988; accepted Aug 11, 1988. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.
Reprint requests to (T.E.W.) 9016 First Aye, Silver Spring, MD 20910.
PEDIATRICS (ISSN 0031 4005). Copyright © 1989 by the American Academy of Pediatrics.
tings with concurrent hypotension and hypoxemia were associated with more damage in the trachea than high settings alone (P = .0019). Factors that affect tissue oxygenation or cause direct trauma appear to influence the degree of histopathologic alterations during mechan-ical ventilation. Pediatrics 1989;84:304-311; airway in-jury, newborn piglets, asphyxia, hypotenaion, mechanical
ventilation.
Tracheobronchial histopathologic alterations
may occur in sick newborn infants following any
type of mechanical ventilation.’ We have
previ-ously described such findings in premature baboons
following conventional positive pressure ventila-tion, high-frequency oscillatory ventilation, and
high frequency flow interruption.5 The changes
were similar and relatively mild for animals
venti-lated with positive pressure and high-frequency
oscillation. However, injury following high-fre-quency flow interruption was substantially greater and characterized by extensive necrosis, diffuse
in-flammatory changes, and intraluminal debris.
These are the findings of necrotizing
tracheobron-chitis, a severe form of airway injury that is
fre-quently fatal. The changes of necrotizing tracheo-bronchitis may be found in as many as 64% to 91%
of autopsied neonates who died following mechan-ical ventilation.9”0 Multiple mechanisms have been suggested as potential causes of necrotizing trach-eobronchitis.26”#{176}’6 However, to date, there have been few investigations evaluating the relative con-tribution of these factors.5”6 In our clinical expe-rience and in that of others,1’’3 necrotizing
trach-eobronchitis occurred in the most severely ill
asphyxia, hypotension, and high ventilator settings.
We designed this investigation to assess the roles
of the following factors in the propagation of tra-cheobronchial injury during conventional mechan-ical ventilation: (1) hypotension; (2) hypoxemia; and (3) “high” vs “low” ventilator settings.
METHODS
Animal
Preparation
We immobilized 53 purebred Chester-White pig-lets aged 3 to 5 days and weighing 1.2 to 3.1 kg with an IM injection of ketamine (20 mg/kg) and
xyla-zine (2 mg/kg). The animals were anesthetized with
15 mg/kg of IV sodium pentobarbital. IV doses of
the latter medication (5 to 10 mg/kg) were
subse-quently administered when necessary. The carotid
artery was cannulated for arterial BP measurement
and blood sampling. Either a peripheral venous
catheter or an external jugular catheter was in-serted for infusion of fluids and medications. We
gave a continuous infusion of 6 mL/kg per hour of
Ringer’s lactate. The arterial line was periodically flushed with 0.5 mL of a solution of 0.9% sodium
chloride containing 2 U/mL of heparin. The
ani-mals were intubated with size 3.0 uncuffed
endotra-cheal tubes. The endotracheal tubes were securely
fastened and the animals sedated such that they
did not move during the experiment and allow the
endotracheal tube to slide up and down. We
per-formed no suctioning of either the tube or of the
airway of the piglet. Arterial blood gas samples were
intermittently obtained from all animals during the
course of ventilation. The blood gas specimens were analyzed on the IL System 1301 pH/blood gas
analyzer (Instrumentation Laboratories, Hudson,
MA). Rectal temperatures were maintained at 38#{176}C by heating pads, heat lamps, external
blan-kets, and warmed IV fluids, when necessary. We
used the HP78532A cardiorespiratory monitor
(Hewlett-Packard Company, Waltham, MA) to
monitor vital functions.
Protocol
Control Group (n = 3). The control animals
con-sisted of two nonintubated, nonventilated piglets
and a third intubated, nonventilated animal. The
piglets were sedated and monitored for 8 hours. We used a randomized block design to assign the remaining 50 animals to the six treatment groups. All piglets were mechanically ventilated for a total
of 8 hours. For all groups, airway humidification
was accomplished with either the Conchatherm
warmed mist humidifier (Respiratory Care, Inc,
Arlington Heights, IL) or the InterMed Bear
hum-idifier (Bear Medical Systems, Inc, Riverside, CA).
The temperature of the inspired gases was
main-tamed at 33#{176}to 35#{176}C.
Group 1. Conventional Positive Pressure
Venti-lation at Low Settings With Neither Hypotension nor Hypoxemia (n = 8). We used a standard infant ventilator, the Bourns BP200 (Bear Medical Sys-tems). The settings were as follows: an Fi02 of 0.25, a rate of 10 breaths per minute, a peak inspiratory pressure of 20 cm of H2O, a positive end expiratory pressure of 4 cm of H20, a flow rate of 10 L/min,
and an inspiratory time to expiratory time ratio of
1:2.
Group 2. Positive Pressure Ventilation at Low
Settings With Initial Hypotension (n = 8). During
the first hour of ventilation, we produced a
hem-orrhagic hypotension in these subjects by connect-ing the carotid arterial line to an anticoagulated
pressure reservoir that was maintained at 35 mm
Hg (normal neonatal piglet mean arterial BP is 70
to 80 mm Hg). After equilibration, the hypotension
was sustained for a total of 30 minutes. The blood
in the reservoir was subsequently transfused back
into the animal. The BP200 settings were the same
as those in group 1 for the 8 hours of ventilation.
Group 3. Positive Pressure Ventilation at Low
Settings With Initial Hypoxemia (n = 8). We
pro-duced hypoxemia during the first hour of
ventila-tion by exposing this group to an Fi02 of 0.05 for
30 consecutive minutes. An arterial blood gas
sam-ple was obtained prior to increasing the Fi02 back
to 0.25, where it remained for the duration of yen-tilation. The positive pressure ventilation settings were identical to those of group 1.
Group 4. Positive Pressure Ventilation at Low
Settings With Both Hypoterision and Hypoxemia (n
= 10). During the first hour of mechanical
ventila-tion, these animals were simultaneously subjected
to hypotension and hypoxemia (as described for
groups 2 and 3) for a total of 30 minutes. Following this period and the reinfusion of blood, mechanical ventilation was maintained at the aforementioned low settings for a total of 8 hours.
Group 5. Positive Pressure Ventilation at High Settings With Neither Hypotension nor Hypoxemia (n = 8). During the 8 hours of the experiment, the
settings on the conventional ventilator for this
group were: an Fi02 of 0.25, a rate of 40 breaths per
minute, a peak inspiratory pressure of 40 cm of
H20, a positive end expiratory pressure of 4 cm of
H20, a flow rate of 17 L/min, and an inspiratory time to expiratory time ratio of 1:2.
Group 6. Positive Pressure Ventilation at “High”
Settings With Both Hypotension and Hypoxemia (n
con-current hypotension and hypoxemia as previously described. The ventilator settings were otherwise
identical to those of group 5 for the 8 hours of
ventilation.
Tissue
Preparation
At the end of the 8-hour ventilation period,
eu-thanasia was accomplished with an overdose of
pentobarbital. The heart and lungs were removed
en bloc. The location of the endotracheal tube tip
within the trachea was identified in situ and marked
with a ligature prior to removal of the tube. The
trachea, bronchi, and lungs were fixed by inflation at low pressure with 10% neutral buffered formalin.
We
measured the external diameter of the trachea1.0 cm
below
the endotracheal tube tip and 1.0 cm above the tip and calculated a ratio of these values. In addition, we measured the distance from thetube tip to the carina.
Following fixation, the trachea and bronchi were
dissected free and removed. We took two transverse
sections from the trachea at least 1.0 cm below the
endotracheal tube tip. From the remaining
speci-men, we made multiple longitudinal sections
ex-tending into both mainstem bronchi. One trans-verse section was examined with a scanning elec-tron microscope. The other transverse section and the longitudinal sections were embedded in paraffin and stained with the periodic acid-Schiff reaction
and with hematoxylin and eosin.
The areas specifically evaluated for light micro-scopic alterations included the entire transverse
tracheal section and the two epithelial surfaces
from the bisected longitudinal sections. From the
latter samples, we examined the trachea for a
dis-tance of 0.5 cm above the carina, the carina, and
both mainstem bronchi for a distance of 0.5 cm
below
the carina. During the histologic review, the examiners were unaware of the treatment of mdi-vidual animals.All slides were scored using the four-point,
seven-variable histopathologic scoring system we
previ-ously
described
(Table
1).56 The variables chosenfor analysis were based on light-microscopic
path-ologic alterations, including: (1) loss of
intraepithe-hal
mucus-presence or absence of goblet cellscon-taming mucus; (2) loss of surface cilia; (3)
submu-cosal hemorrhage-absent, minimal, or severe; (4)
surface epithelial changes-hyperplasia, squamous
metaplasia, or loss of the entire epithelium; (5)
polymorphonuclear leukocytic infiltration-scat-tered or dense, focal or diffuse; (6) epithelial
ero-sion-denuding of epithelial cells from the
base-ment membrane; and (7) necrosis-cell death with
or without inflammatory infiltration. Individual
in-jury scores were assigned for each variable. Total
injury scores (the sum of all seven variables) were
calculated for each of the areas examined. The
sections were independently evaluated. When
dif-ferences in injury scores were noted, the slides were
jointly examined and consensus scores were
as-signed. Examples of normal light and scanning
electron microscopic sections are shown in Figs 1 and 2.
Data Analysis
Injury scores were compared by two-way analysis
of variance, the Kruskal-Wallis test, and the Mann-Whitney test. A P
value
of .05 or less was consideredto be statistically significant. To evaluate continu-ous variables, we used Student’s t test with Bonfer-roni’s correction for multiple comparisons.
RESULTS
Two piglets from the low positive pressure
yen-tilation-concomitant hypotension and hypoxemia group (group 4) died during these interventions. They were not included in any further comparisons. Characteristic features of the remaining 51 piglets are shown in Table 2. There were no statistically
significant differences in the male to female sex
ratios, birth weights, hematocrits, the distance of
the endotracheal tube tip from the carina, the
ar-terial partial pressure of oxygen during hypoxemia,
or the amount of blood removed during
hypoten-sion. However, the distal to proximal external
tra-cheal ratios were significantly greater in both
groups receiving positive pressure ventilation at
high settings compared with the four low settings
groups (P < .01).
The total injury scores for the three control
ani-mals were either 0 or 1. The mean injury scores of
the remaining animals are shown in Figs 3 and 4.
The histologic changes were mild among groups 1
to 3 of the piglets receiving positive pressure yen-tilation at low settings. However, group 4 piglets
(low settings with concomitant hypotension and
hypoxemia) had significantly greater injury scores
in all areas (P < .004) than the other three low
positive pressure ventilation groups and the high
settings without concurrent hypotension and
hy-poxemia group (group 5). The changes in the group
4 animals were manifested by submucosal
hemor-rhage, cilia loss, goblet cell loss, erosions, and scat-tered inflammation (Figs 5 and 6). The group re-ceiving positive pressure ventilation at high settings
with no hypotension or hypoxemia (group 5) had
---..-
-c.-
- - * -‘:
-:
a.#{231}-r-..-
r-p -_1;,.-.- btl
TABLE 1. Histologic Scoring System
Histologic Finding Score
0 +1 +2 +3 +4
Intraepithelial mucus loss Absent Focal Diffuse
Cilia loss Absent Focal Diffuse
Submucosal hemorrhage Absent Minimal Severe
Surface epithelial changes Absent Hyperplasia Squamous metaplasia Entire loss of
epithelium
Polymorphonuclear leukocyte Absent Focal, scattered Focal, dense Diffuse, scat- Diffuse, dense
infiltration tered
Epithelial erosions Absent 1 area 2-3 areas >3 areas or
an exten-sive area
Total
Necrosis Absent 1 area 2-3 areas >3 areas or
an exten-sive area
Total
Fig 1.
Light microscopic section of normal upper airway epithelium. There are pseudocolumnar epithelium, abun-dant surface cilia, and numerous mucus-containing gobletcells (magnification x20).
settings. However, high settings combined with
hy-potension and hypoxemia led to more damage in
the trachea than the use of higher settings alone (P
= .0019). The histologic changes and injury scores
were similar in the tracheae of both combined
by-potension/hypoxemia groups (groups 4 and 6). In
all animals, the damage was significantly greater in
the more cephalad transverse tracheal sections (Fig
7, P < .008) compared with the lower longitudinal sections. The changes in the most severely injured transverse sections were extensive and character-ized by widespread epithelial erosions, necrosis,
diffuse inflammation, and intraluminal debris (Fig
8).
We found numerous “skip” areas of injury
throughout the trachea. At the same level, there
could
be noticeably different pathologic findings. There could be areas that appeared normal withareas of severe injury opposing them at the same
level.
A normal or mildly altered section could be“sandwiched” between areas of extensive damage.
The most severe injury, however, was consistently
Fig 2. Scanning electron microscopic section of normal upper airway epithelium revealing “wheat-like” fields of
cilia and protruding goblet cells (magnification x2300).
present in the upper trachea closer to the endotra-cheal tube tip (still at least 1.0 cm below the tip).
DISCUSSION
In this investigation, we examined the roles of several potential determinants of airway injury. We found no difference in the severity of injury between
OPPY: NO IBP. NO 102
PPV:1BP #{149}PPV:102 DPPV: BOTHIBP,102
14
12
10
8
6
4 2
C,,
w
14
DPPv (HIGH SETTiNGS):NOl BP. NO 102 Ppv (HIGH SETTINGS):BOTHIBPAND 102
i:
6-TRACHEA CARINA RMSB LMSB
TABLE 2.
Characteristics of Study Piglets*Group No. Sex Mean Mean Endotracheal Mean Distal to Mean Pao2 Mean Blood
(No.) Wt Tube Distance Hematocrit Proximal at End of Removed for
M F (kg) From Carina (cm) (%) Trachea Ratio Hypoxemia Hypotension (mL)
Control 3 1 2 2.27 2.5 24 1.0:1
1 8 6 2 1.91 2.9 29 0.99:1
2 8 2 6 2.04 2.6 25 1.02:1 26
3 8 7 1 2.05 3.0 28 1.04:1 23
4 8 3 4 2.00 2.6 28 1.01:1 23 21
5 8 4 4 2.27 2.7 26 1.19:lt
6 8 6 2 2.26 2.8 29 1.15:lt 28 19
* Positive pressure ventilation treatment groups were defined as follows: group 1, at low setting with no hypotension
or hypoxemia; group 2, at low settings with hypotension; group 3, at low settings with hypoxemia; group 4, at low settings with both hypotension and hypoxemia; group 5, at high settings with no hypotension or hypoxemia; group 6, at high settings with both hypotension and hypoxemia.
Fig 3.
Mean total injury scores for animals in groups 1to 4 (conventional ventilator at lowsettings). Scores were significantly greater in positive pressure ventilation group with concomitant hypotension and hypoxemia in all areas examined (P < .004). Abbreviations: PPV, pos-itive pressure ventilation; RMSB, right mainstem bron-chus; LMSB, left mainstem bronchus.
inspiratory pressure) and high settings. Moreover,
neither severe hypotension nor hypoxemia alone
led to more extensive changes. However, the
com-bination of these latter two factors did result in significantly greater injury scores. The histologic
changes in the combined hypotension and
hypox-emia animals (groups 4 and 6) resemble the more
severe changes found in piglets we have ventilated for 8 hours with the high-frequency flow
interrup-tion-continuous pulsation strategy.laa This device
and strategy led to necrotizing tracheobronchitis in
68% of premature baboons ventilated in this
man-ner.5
Histologic
alterations are a frequentcomplica-tion of endotracheal intubation and mechanical
ventilation.”2’5’6’9”#{176} The most severe manifestation
of these changes is necrotizing tracheobronchi-tis.3’4’9’3 Multiple mechanisms have been suggested as potential causes of the extensive damage of nec-rotizing tracheobronchjtis.26’9”#{176}”2’8 However, to
TRACHEA CARINA RMSB LMSB Fig 4. Mean total injury scores for animals in groups 5 and 6 (conventional ventilator at high settings). Scores were significantly greater (P = .0019) in tracheae of the piglets with concurrent hypotension and hypoxemia. Ab-breviations: PPV, positive pressure ventilation; RMSB, right mainstem bronchus; LMSB, left mainstem bron-chus.
/
. ... : , ,: : ‘. .- . , #{149}A. #{149}-#{149},-_‘,J.l .#{149}\:-‘. : ‘.#{149}.
- ‘ . . . . ii; . - -, ‘
- .
.,
-‘.%.. .-- *. ..
-. .
‘4.
..1;-,:
...---..
_s-I #{149} ‘:Z1-.
Fig 6. Findings on scanning electron microscopy of tra-cheae of piglets with concurrent hypotension and hypox-emia. Note scant cilia, loss of goblet cells, and erosion of surface epithelium (magnification xllOO).
(I, w
0
0 U,
a:
:,
z
a:
z
PPV: PPV: PPV: PPV: High: High:
none BP 02 both none both
Fig 7. Mean airway injury scores of upper transverse tracheal sections compared with scores of lower longitu-dinal sections (none = no hypotension or hypoxemia, BP = hypotension, 02 hypoxemia, both = both hypotension and hypoxemia). Scores are significantly greater in upper trachea (P < .008). Abbreviation: PPV, positive pressure ventilation.
date, there have been few investigations in which
the relative contributions of these factors were eval-uated.5”6”8 The lack of adequate humidification of inspired gases adversely affects the respiratory
Fig 8.
Light microscopic findings in upper transverse tracheal sections. There are no cilia or goblet cells; there is diffuse inflammation and hemorrhage, as well as com-plete denudation of the epithelial surface; and intralu-minal debris is present (magnification x20).epithelium.’7”8 Mammel et al’6 described tracheal
injury following high-frequency jet ventilation of adult cats. These authors suggested that increasing ventilator frequency was responsible for the sever-ity of damage. We previously found mild histologic
changes in premature baboons following
conven-tional (n = 25) and high-frequency oscillatory (n =
32) ventilation.5 By contrast, we found necrotizing tracheobronchitis in 17 of 25 animals ventilated with the high-frequency flow
interruption-contin-uous strategy (at the same frequency of 10 Hz and
similar proximal mean airway pressures as the
high-frequency oscillatory ventilation baboons). The latter high-frequency devices generally operate
at frequencies greater than those used with
high-frequency jet ventilation. Our findings would
seem-ingly “exonerate” higher frequency, per Se, and
“implicate” the particular device or strategy used
as the cause of increased damage. There is no
evidence that the duration of mechanical
ventila-tion is directly related to the development of
nec-rotizing tracheobronchitis. Brodsky et al’9 de-scribed epithelial erosions within 3 hours of initia-tion of ventilation in fetal lambs. Cordero et al20’2’ found necrotizing tracheobronchitis after ventilat-ing newborn piglets for only 6 hours. In our previous studies,5 using conventional and high-frequency ventilation (both high-frequency oscillatory
venti-lation and high-frequency flow interruption), we
did not find an increasing severity of injury in
premature baboons as the duration of ventilation
increased from 24 to 264 hours. In addition, there
was no more extensive damage when we used 100%
oxygen compared with oxygen given as the occasion
ventila-tion, high-frequency oscillatory ventilation, and high-frequency flow interruption devices.7’8
The newborn piglet served as an important model
for the research of numerous pulmonary diseases
and ventilatory devices.2#{176}26 Cordero et al20’21 pre-viously used the animal as a model for developing
tracheobronchial injury. Moreover, the piglet has
been used for investigations of asphyxia and
hypo-tension.27 The usefulness of this model in the eval-uation of airway damage is substantiated by our experience.
Necrotizing tracheobronchitis has been described
following both conventional and high-frequency
ventilation.3’4’9’3 It has been postulated that
nec-rotizing tracheobronchitis represents an ischemic
injury related to the intraluminal tracheal pressure effects on mucosal and submucosal blood flow.’5 The findings of greater damage in the upper trachea lead us to believe there are two major categories of mechanisms that influence airway histologic
changes (Appendix). The first encompasses
intra-luminal elements that directly traumatize the
epi-thelial surfaces. Some of these factors may be
tur-bulent flow, high-velocity gas streams (causing
shear stress or the jackhammer effect), and
flow-directed damage due to the bevel of the
endotra-cheal tube tip. The second broad category consists of factors that impair tissue oxygenation. These determinants may include hypoxemia, hypotension, right to left shunting, and stinting of capillary blood flow. It is likely that when multiple factors are
present more extensive damage can result.
As many as 64% of conventionally ventilated
neonates may have findings of necrotizing
trach-eobronchitis at autopsy.9”3 Of autopsied nonsurvi-vors of high-frequency jet ventilation, 91% show
histologic evidence of necrotizing
tracheobronchi-tis.’#{176}Because necrotizing tracheobronchitis is
pre-sent so often in neonates who die, we suspect the
entity plays an unpropitious role during the clinical course of numerous diseases seen among sick
new-borns. Nonfatal necrotizing tracheobronchitis may
contribute to the need for increased ventilator
set-tings, pulmonary air leaks, tracheal stenosis, and
chronic lung disease. Mammel et al’#{176}have suggested that strategies to prevent necrotizing
tracheobron-chitis should be similar to those used to prevent
bronchopulmonary dysplasia. However, our
find-ings have demonstrated no difference in airway
histology among animals treated with either high
concentrations of oxygen7 or high ventilator
set-tings (peak pressure, frequency, and flow rate). We
believe that until all possible determinants of the
malady are ascertained, we may be unable to modify
or avoid the course of necrotizing
tracheobronchi-tis.
In conclusion, among piglets mechanically yen-tilated for 8 hours, high conventional ventilator
settings alone do not alter airway histology any
more than do low settings. A combination of
hy-potension and hypoxemia leads to more extensive
tracheobronchial changes than the absence of these
factors or the presence of either factor alone. We
speculate that early use of high concentrations of
oxygen and judicious fluid resuscitation may
pre-vent or mitigate the course of necrotizing tracheo-bronchitis.
ACKNOWLEDGMENTS
We acknowledge the advice, comments, and support of Drs Donald G. Corby, Jeffrey M. Linn, James McNeil, and August J. Salvado. We also thank Barbara Cunegin and Joyce Powell.
Appendix: Factors Potentially Exacerbating Tracheobronchial Histologic Changes During Mechanical Ventilation
Physical Characteristics of the Ventilator Device Itself 1. Strategy used with particular devices:
High oxygen concentrations High frequency
High
flow ratesContinuous high frequency flow interruptor strat-egy
Gas waveform
Excessive tidal volume Insufficient expiratory time High peak or mean pressures 2. Mechanisms of gas delivery:
High velocity gas stream leading to the “jackham-mer” effect or shear stress
Flow directed damage by the bevel of the endotra-cheal tube tip
Turbulent flow in the larger airways 3. Inadequate gas humidification
4. Excessive airway temperature
5. Chemical irritation from tubing constituents 6. Particulate matter assicuated with device
Frequency and Methods of Suctioning 1. Endotracheal tube factors:
Size of endotracheal tube Duration of intubation
Number of times infant is intubated and reintu-bated
Expertise and techniques of the intubator “Pistoning” of the endotracheal tube 2. Duration of ventilation
3. Patient’s disease state
4. Compromise of tissue oxygenation: Hypotension
“Stinting” of capillary blood flow
Compromise of “watershed” area of airway circula-tion
Right to left shunting REFERENCES
Rasche RFH, Kuhns LR. Histopathologic changes in air-way mucosa of infants after endotracheal intubation. Pe-diatrics. 1972;50:632-637
2. Joshi VV, Mandavia MB, Stern L, et al. Acute lesions induced by endotracheal intubation. Am J Dis Child.
1972;124:646-649
3. Boros SJ, Mammel MC, Lewallen PK, et al. Necrotizing tracheobronchitis: a complication of high-frequency venti-lation. J Pediatr. 1986;109:95-100
4. Kirpilani H, Higa T, Perlman M, et al. Diagnosis and therapy of necrotizing tracheobronchitis in ventilated neo-nates. Crit Care Med. 1985;13:792-797
5. Clark RH, Wiswell TE, Null DM, et al. Tracheal and bronchial injury in high-frequency oscillatory ventilation compared with conventional positive pressure ventilation.
J Pediatr. 1987;111:114-118
6. Wiswell TE, Clark RH, Null DM, et al. Tracheal and bronchial injury in high-frequency oscillatory ventilation and high-frequency flow interruption compared with con-ventional positive pressure ventilation. J Pediatr. 1988;112:249-256
7. Wiswell TE, Clark RH. The effect of 100% oxygen on the propagation of tracheobronchial injury during high fre-quency and conventional ventilation. Pediatr Res. 1988:23:530A. Abstract
8. Wiswell TE, Clark RH, Null DM, et al. Tracheal and bronchial injury with high frequency oscillatory and high frequency flow interruption compared with conventional
positive pressure ventilation. Pediatr Pulmonol. 1987;3:376 9. Gaylord MS, Quissell BJ, Lair ME. High-frequency venti-lation in the treatment of infants weighing less than 1,500 grams with pulmonary interstitial emphysema: a pilot study. Pediatrics 1987;79:915-921
10. Mammel MC, Boros SJ. Airway damage and mechanical
ventilation: a review and commentary. Pediatr Pulmonol.
1987;3:443-447
11. Fox WW, Spitzer AR, Smith D, et al. Tracheal secretion impaction during hyperventilation for persistent pulmo-nary hypertension of the neonate. Pediatr Res. 1984;19:323A. Abstract
12. Mimouni F, Ballard JL, Ballard ET, Cotton RT. Necrotiz-ing tracheobronchitis: case report. Pediatrics. 1986;77:366-368
13. Pietsch JB, Nagaraj HS, Groff DB, et al. Necrotizing tracheobronchitis: a new indication for emergency bron-choscopy in the neonate. J Pediatr Surg. 1985;20:391-393
14. Minton D, Stoddard RA, Lassen G, et al. Silicone particu-late debris in the life pulse high frequency jet ventilator. Pediatr Pulmonol. 1987;3:375
15. deLemos RA, Gerstmann DR, Clark RH, et al. High fre-quency ventilation-the relationship between ventilator design and clinical strategy in the treatment of hyaline membrane disease and its complications: a brief review. Pediatr Pulmonol. 1987;3:370-372
16. Mammel MC, Ophoven JP, Lewallen PK, Gordon MJ, Sutton MC, Boros SJ. High-frequency ventilation and tra-cheal injuries. Pediatrics. 1986;77:608-613
16a. Wiswell TE, Bley JA, Turner BS, et al. Propogation of tracheobronchial histopathologic changes and effect of dif-ferent high frequency ventilator strategies. Pediatrics. In press
17. Chalon J, Loew DAY, Malebranche J. Effects of dry anes-thetic gases on tracheobronchial ciliated epithelium.
Anes-thesiology. 1972;37:338-343
18. Marfatia S, Donahoe PK, Hendren WH. Effect of dry and humidified gases on the respiratory epithelium in rabbits. J Pediatr Surg. 1975;10:583-592
19. Brodsky L, Naviwala S, Stanievich JF. A quantitative comparison of the early histopathological changes from
tracheotomy and endotracheal intubation on the distal trachea in fetal lambs.
mt
Pediatr Otorhinokiryngol. 1987;12:273-28220. Cordero L, Tallman RD, Qualman SJ, et al. Necrotizing tracheobronchitis in the piglet following high-frequency ventilation. Pediatr Res. 1987;21:446A. Abstract
21. Cordero L, Tallman R, Qualman S. Necrotizing tracheo-bronchitis (NTB) following high frequency ventilation: ef-fect of lung deflation. Pediatr Res. 1988;23:502A. Abstract 22. Hammerman C, Komar K, Abu-Khudair H: Hypoxic vs
septic pulmonary hypertension. Am J Dis Child.
1988;142:319-325
23. Suguihara C, Bancalari E, Goldberg RN, et al. Hemody-namic and ventilatory effects of high-frequency jet and conventional ventilation in piglets with lung lavage. Biol Neonate. 1987;51:241-248
24. Trindale 0, Goldberg RN, Bancalari E, et al. Conventional vs high-frequency jet ventilation in a piglet model of me-conium aspiration: comparison of pulmonary and hemo-dynamic effects. J Pediatr. 1985;107:115-120
25. Obara H, Maekawa N, Hamatani S, et al. Effect of rapid-rate ventilation on the experimental diseased lung caused by meconium aspiration. Biol Neonate. 1985;48:149-156 26. Mirro R, Busija D, Green D, et al. Relationship between
mean airway pressure, cardiac output, and organ blood flow with normal and decreased respiratory compliance. J
Pe-diatr. 1987;111:101-1O6
