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Variations in inspiratory: expiratory ratio and airway pressure wave form during mechanical ventilation: The significance of mean airway pressure
114
January 1979 The Journal o f P E D I A T R 1 C S
Variations in inspiratory:expiratory ratio and airway pressure wave form during mechanical ventilation: The significance of mean airway pressure Twelve neonates with severe lung disease were studied while mechanically ventilated with volume pre-set infant ventilators, using different I:E ratios and different airway pressure waves. While Floe tidal volume, respiratory rate, and PEEP remained constant, I:E ratios were increased, first by reducing inspiratory flow rate, which produced a triangular pressure wave, and then by using an inspiratory time hold mechanism, which produced an inspiratory plateau or squared pressure wave. Peak inspiratory pressure, mean airway pressure, Paoe Pacoz, pH, and blood pressure were measured and compared for each I:E ratio and pressure wave combination. In all patients, increases in oxygenation appeared to be directly related to increases in MAP. Optimum oxygenation and ventilation occurred with the I:E ratio and pressure wave combination that produced the highest MAP. Because M A P changes with any alteration in PEEP, I:E ratio, or airway pressure wave, it is a clinically useful composite measure of all pressures transmitted to the airways by a mechanical ventilator.
Stephen J. Boros, M . D . , St. P a u l , M i n n .
A RECENT ANIMAL STUDY from this institution examining the relationship between inspiratory:expiratory ratio and positive end expiratory pressure showed the value of mean airway pressure as a composite measure of all pressures transmitted to the airways by a mechanical ventilator. 1 That study, and those of Herman and Reynolds? also showed a direct relationship between MAP, and oxygenation and ventilation. Oxygenation and ventilation are also said to be influenced by the shape of the airway pressure wave induced by a mechanical ventilator? -'; The purpose of this study is to examine the effects of various MAP, I:E ratio, and airway pressure wave combiFrom The Children's Hospital, and the Department of Pediatrics, University of Minnesota. Aided by the Research and Education Fund of The Children's Hospital. Read in part before the annual meeting of the Midwest Society Jbr Pediatric Research, St. Louis, November 17, 1977. Reprint address The Children's Hospital, 311 Pleasant A re., St. Paul MN 55102,
Vol. 94, No. 1, pp. 114-117
nations on human neonates during controlled mechanical ventilation. Abbreviations used I:E Ratio: inspiratory:expiratory ratio FI02: fraction of oxygen in inspired air PEEP: positive end expiratory pressure MAP: mean airway pressure Pao: partial pressure of arterial oxygen Paco~: partial pressure of arterial carbon dioxide
PATIENTS AND METHODS Twelve neonates receiving controlled mechanical ventilation were selected for study. Eight had hyaline membrane disease, three had aspirated meconium, and one had aspirated blood. All were paralyzed with pancuronium bromide and ventilated with volume pre-set infant ventilators. When studied, most were deteriorating on what, at the time, were considered to be standard ventilatory settings. The infants (Table I) ranged in weight from 920 to 3,900 gm and in gestational age from 27 to 42 weeks. The mean birth weight was 2,134 gm, mean gestational age 34
0022-3476/79/100114+04500.40/0 9 1979 The C. V. Mosby Co.
Volume 94 Number 1
weeks, and mean age at the time of study was 20 hours. Mean FIo~ at the time of study was 0.85, mean peak inspiratory pressure 55 cm H20, mean PEEP 6 cm H20, mean rate 30/minute, and mean effective tidal volume (machine tidal volume minus volume lost within the ventilator) was 8.7 ml/kg. The mean arterial blood gas values at these settings were: Pao~ 69 mm Hg, Paco z 46 mm Hg, and pH 7.32. The equipment used in this trial (Bourns Infant Ventilator LS- 104-150; Bourns Ventilator Monitor LS- 160) had an inspiratory hold mechanism that allowed I:E ratios to be increased either by decreasing inspiratory flow rate, previously the only way to change I:E ratio, or by using the inspiratory time hold while keeping inspiratory flow rate constant. Changing the I:E ratio by using these two techniques produced different airway pressure wave forms (Fig. I). The airway pressure wave of this ventilator at an I:E ratio of 1:4 was a triangle. As the I:E ratio was increased to l : l by decreasing inspiratory flow, the wave remained a triangle but became elongated, Increasing the I:E ratio using the inspiratory time hold mechanism produced a plateaued or squared wave. These were the pressure wave forms examined. At the beginning of each trial a steady state was achieved at an inspiratory flow rate that produced an I:E ratio of 1:4. The FIo=, tidal volume, rate, and PEEP were adjusted to provide maximum ventilation and oxygenation at this baseline and were not altered thereafter. The I:E ratio and airway pressure waves were then varied in the following sequence: (l) 1:4, triangular wave; (2) l : l , decreasing inspiratory flow rate producing elongated triangular wave; (3) 1:4, triangular wave; and (4) l : l , using the inspiratory time hold, producing a squared wave. Ten patients were studied in this sequence, two other patients were ventilated using slightly different I:E ratio wave combinations and were considered separate-
ly. After a 15 to 20 minute equilibration period at each I:E ratio, pressure wave combination, Pao2, Paco2, pH, peak inspiratory pressure, MAP, and blood pressure were measured. Because patients were ventilated at various oxygen concentrations, individual changes in arterial oxygenation were standardized by the expression P a o J FIo~.7-9 Airway pressures were measured at the operating head of the ventilator using a standard pressure transducer (Hewlett-Packard HP1280C) and a standard processor display module (Hewlett-Packard HP8205B). This system has a signal processor that uses an integrator circuit to calculate mean pressures over 12 seconds. Blood pressures were monitored through umbilical artery catheters using the same system. Both airway pressure and blood pressure monitoring systems were attached to a two channel
Significance of mean airway pressure
1 15
•/rwoy Pressure Wave Forms
I:Eratio 5oF-
~,
L
I :4
//I/
/
//
,/ i
/ i
0 l:l
(A flow)
/
/
i
/
/! 4 9
/ /
L~ . . . .
//~A ......
/
o
(insp.l:lhold)501
///. . . . . ~. . . . . ,,/
]
/
/ /
0 Iq
2 sec
ml
Fig. 1. The different airway pressure waves produced while increasing I:E ratio either by decreasing inspiratory flow rate or by employing the inspiratory time hold mechanism.
Table I. Summary of clinical data
Birth weight (gin) Gestational age (wk) Age studied (hr) Flo2 Peak inspiratory pressure (cm H20) PEEP (cm H20) Effective tidal volume (ml/kg) Rate (per minute) Pao~ (ram Hg) Paco~. (ram Hg) pH
Mean +_ SD
] Range
2,134 34 20 0.85 55
920-3,900 27-42 8-72 0.55-I.0 37-94
_+ 890 __+4 _+ 17 +_ 0.17 _ 15
6 _+ 0.9 8.7 _+ 1.3 30 _ 4 69 + 36 46 _+ 9 7.32 _+ 0.5
4-7 7-I1 25-35 24-147 37-66 7.2-7.41
recorder (Hewlett-Packard HP7402A). Statistical analysis was performed using a two-tailed t test. RESULTS Changes in mean arterial blood gases and mean blood pressures in response to changes in ventilator settings are displayed in Fig. 2. A listing of all ventilator variables, arterial blood gas measurements, blood pressure measurernents, and MAP measurements is available on request. As I:E ratios were increased from 1:4 to l : l by decreasing inspiratory flow rate, elongated triangular pressure waves were produced, and arterial oxygenation improved (P < 0.05). There was little change in Paco2 or arterial blood pressure. Returning to the baseline I:E ratio of 1"4, both MAP and Pao2/FIo2 returned to near the original baseline values.
116
o_~ rn~
Boros
The Journal of Pediatrics January 1979
60~
//
250
4o
200 200 o
~ c~ t50
}50
LL
c~
80 I00
E9 40 8'
50
c~
o
13-
I00
50
o o
I
I
]:4
I:1 (r, fl0w)
I
I
1:4
I:1 (insp.bld)
Inspiratory/ExpiratoryRatio Fig, 2. Changes in arterial blood gases and blood pressure
associated with changes in I:E ratios and airway pressure waves (Pao2/FIo=' _+ 1 SEM). Table II
Patient
MAP (cm H~O)
I:E ratio
Pressure wave
B.W.
32
1:1
Square Triangle Square Triangle Square Triangle Square Triangle
1:4
B.E.
26
1: 1 1:4
M.M.
19
m.G.
35
1:1 1:4 1:1 1:4
PEEP (cm H20)
PaoJ Fio2
4 16 7 17 5 12 5 18
187 224 257 420 186 170 222 327
Increasing I:E ratios from 1:4 to 1:1 using the respiratory time hold produced squared pressure waves and more than a twofold increase in P a o / F [ o ~ followed (P < 0.001). There was no significant change in either Paco 2 or arterial blood pressure. The P a o / F l o 2 value obtained at an I:E ratio of 1:1 using the squared airway pressure wave was significantly greater than that obtained at an I:E ratio of 1:1 using the elongated triangular wave (P < 0.001). In Fig. 3 is shown the changes in mean Pao /FIo~ values in terms of MAP alone. In all patients the P a o J F [ o~ increased a MAP increased. In all patients the best oxygenation occurred at the highest MAP and in all, highest MAP was achieved with the squared pressure wave. The significance of the shape of the airway pressure wave was examined in a separate clinical trial involving four infants ventilated at similar MAPs using both the triangular and squared wave forms. This was done by raising the PEEP of the triangular wave until an MAP
0
1
I
I
(
l
10 15 2O 25 30 MeanAirwayPressure(cmHzO)
Fig. 3. Mean changes in Pao/Flo~ associated with changes in MAP.
similar to that obtained with the squared wave was achieved (Table II). There were no significant differences in the mean Pao2/FIo2 values obtained with the two different pressure waves (P = 0.164). DISCUSSION Prolonging the inspiratory phase of the respiratory cycle during mechanical ventilation has become an accepted technique for improving arterial oxygenation. Reynolds, when restricting the peak inspiratory pressure of pressure pre-set ventilators observed that increases in I:E ratio produced plateaued or squared airway pressure waves and that significant increases in Pao2 followedP 6 Herman and Reynolds, 2 using pressure pre-set ventilators, noted that increased I:E ratios and modest amounts of PEEP acted synergistically to improve arterial oxygenation. Gains in oxygenation were thought to be due to increases in MAP, the mean pressure transmitted to the airways throughout both inspiration and expiration. Recent animal studies from our laboratory examined the relationship between I:E ratio and PEEP using volume pre-set infant ventilators.' These ventilators produced triangular pressure waves, not squared waves. We also observed that MAP was the ventilator measurement most closely related to arterial oxygenation. The present study, examining the relationship between I:E ratios and airway pressure waves, using constant tidal volume ventilators, also suggests that MAP is the best indicator of arterial oxygenation. In all cases, optimum oxygenation was achieved with the I:E ratio and pressure wave combination that produced the highest MAP. In all cases this pressure was achieved with the squared pressure wave. However, the shape of the airway pressure wave per
Volume 94 Number I
se does not appear to be particularly significant. Rather, the shape of the wave seems important only because of the changes it causes in MAP. Mean airway pressure is determined by calculating the area beneath the pressure curves of both inspiration and expiration, then dividing that area by its appropriate time. Prolonging inspiration by any technique will increase MAP. The inspiratory pressure curve with the greatest area per unit of time will therefore have the highest MAP. Increasing PEEP expands the area beneath the expiratory pressure curve and also increases MAP. Because MAP changes with any alteration of PEEP, I:E ratio, or airway pressure wave form, it is a clinically useful composite measure of all pressures transmitted to the airways by the ventilator. The relationship of MAP to the various complications of mechanical ventilation is presently under investigation.
Significance o f mean airway pressure
2.
3.
4.
5.
6. 7. 8.
REFERENCES
1. Boros SJ, Matalon SV, Ewald R, Leonard AS, and Hunt CE: The effect of independent variations in inspiratoryexpiratory ratio and end expiratory pressure during
9.
1 17
mechanical ventilation in hyaline membrane disease: The significance of mean airway pressure, J PEDIATR91:794, 1977. Herman S, and Reynolds EOR: Methods for improving oxygenation in infants mechanically ventilated for severe hyaline membrane disease, Arch Dis Child 48:612, 1973. Reynolds EOR: Effect of alterations in mechanical ventilator settings on pulmonary gas exchange in hyaline membrane disease, Arch Dis Child 46:152, 1971. BlakeAM, Durbin GM, MacNab AJ, Collins LM, Hunter NJ, and Reynolds EOR: Simplified mechanical ventilation for hyaline membrane disease, Lancet 2:1176, 1973. Reynolds EOR: Pressure wave form and settings for mechanical ventilation in severe hyaline membrane disease, Int Anesthesiol Clin 12:259, 1974. ReynoldsEOR: Management of hyaline membrane disease, Br Med Bull 31:18, 1975. HorovitzJH, Carrico CJ, and Shires T: Pulmonary response to major injury, Arch Surg 108:349, 1974. Kirby RR, Downs JB, Civetta JM, Modell JH, Dannemiller FJ, Klein EF, and Hodges M: High level positive and expiratory pressure (PEEP) in acute respiratory insufficiency, Chest 67:156, 1975. KeighleyGR: The arterial/alveolar oxygen tension ratio. An index of gas exchange applicable to varying inspired oxygen concentrations, Am Rev Resp Dis 109:142, 1974.
January 1979 The Journal o f P E D I A T R 1 C S
Variations in inspiratory:expiratory ratio and airway pressure wave form during mechanical ventilation: The significance of mean airway pressure Twelve neonates with severe lung disease were studied while mechanically ventilated with volume pre-set infant ventilators, using different I:E ratios and different airway pressure waves. While Floe tidal volume, respiratory rate, and PEEP remained constant, I:E ratios were increased, first by reducing inspiratory flow rate, which produced a triangular pressure wave, and then by using an inspiratory time hold mechanism, which produced an inspiratory plateau or squared pressure wave. Peak inspiratory pressure, mean airway pressure, Paoe Pacoz, pH, and blood pressure were measured and compared for each I:E ratio and pressure wave combination. In all patients, increases in oxygenation appeared to be directly related to increases in MAP. Optimum oxygenation and ventilation occurred with the I:E ratio and pressure wave combination that produced the highest MAP. Because M A P changes with any alteration in PEEP, I:E ratio, or airway pressure wave, it is a clinically useful composite measure of all pressures transmitted to the airways by a mechanical ventilator.
Stephen J. Boros, M . D . , St. P a u l , M i n n .
A RECENT ANIMAL STUDY from this institution examining the relationship between inspiratory:expiratory ratio and positive end expiratory pressure showed the value of mean airway pressure as a composite measure of all pressures transmitted to the airways by a mechanical ventilator. 1 That study, and those of Herman and Reynolds? also showed a direct relationship between MAP, and oxygenation and ventilation. Oxygenation and ventilation are also said to be influenced by the shape of the airway pressure wave induced by a mechanical ventilator? -'; The purpose of this study is to examine the effects of various MAP, I:E ratio, and airway pressure wave combiFrom The Children's Hospital, and the Department of Pediatrics, University of Minnesota. Aided by the Research and Education Fund of The Children's Hospital. Read in part before the annual meeting of the Midwest Society Jbr Pediatric Research, St. Louis, November 17, 1977. Reprint address The Children's Hospital, 311 Pleasant A re., St. Paul MN 55102,
Vol. 94, No. 1, pp. 114-117
nations on human neonates during controlled mechanical ventilation. Abbreviations used I:E Ratio: inspiratory:expiratory ratio FI02: fraction of oxygen in inspired air PEEP: positive end expiratory pressure MAP: mean airway pressure Pao: partial pressure of arterial oxygen Paco~: partial pressure of arterial carbon dioxide
PATIENTS AND METHODS Twelve neonates receiving controlled mechanical ventilation were selected for study. Eight had hyaline membrane disease, three had aspirated meconium, and one had aspirated blood. All were paralyzed with pancuronium bromide and ventilated with volume pre-set infant ventilators. When studied, most were deteriorating on what, at the time, were considered to be standard ventilatory settings. The infants (Table I) ranged in weight from 920 to 3,900 gm and in gestational age from 27 to 42 weeks. The mean birth weight was 2,134 gm, mean gestational age 34
0022-3476/79/100114+04500.40/0 9 1979 The C. V. Mosby Co.
Volume 94 Number 1
weeks, and mean age at the time of study was 20 hours. Mean FIo~ at the time of study was 0.85, mean peak inspiratory pressure 55 cm H20, mean PEEP 6 cm H20, mean rate 30/minute, and mean effective tidal volume (machine tidal volume minus volume lost within the ventilator) was 8.7 ml/kg. The mean arterial blood gas values at these settings were: Pao~ 69 mm Hg, Paco z 46 mm Hg, and pH 7.32. The equipment used in this trial (Bourns Infant Ventilator LS- 104-150; Bourns Ventilator Monitor LS- 160) had an inspiratory hold mechanism that allowed I:E ratios to be increased either by decreasing inspiratory flow rate, previously the only way to change I:E ratio, or by using the inspiratory time hold while keeping inspiratory flow rate constant. Changing the I:E ratio by using these two techniques produced different airway pressure wave forms (Fig. I). The airway pressure wave of this ventilator at an I:E ratio of 1:4 was a triangle. As the I:E ratio was increased to l : l by decreasing inspiratory flow, the wave remained a triangle but became elongated, Increasing the I:E ratio using the inspiratory time hold mechanism produced a plateaued or squared wave. These were the pressure wave forms examined. At the beginning of each trial a steady state was achieved at an inspiratory flow rate that produced an I:E ratio of 1:4. The FIo=, tidal volume, rate, and PEEP were adjusted to provide maximum ventilation and oxygenation at this baseline and were not altered thereafter. The I:E ratio and airway pressure waves were then varied in the following sequence: (l) 1:4, triangular wave; (2) l : l , decreasing inspiratory flow rate producing elongated triangular wave; (3) 1:4, triangular wave; and (4) l : l , using the inspiratory time hold, producing a squared wave. Ten patients were studied in this sequence, two other patients were ventilated using slightly different I:E ratio wave combinations and were considered separate-
ly. After a 15 to 20 minute equilibration period at each I:E ratio, pressure wave combination, Pao2, Paco2, pH, peak inspiratory pressure, MAP, and blood pressure were measured. Because patients were ventilated at various oxygen concentrations, individual changes in arterial oxygenation were standardized by the expression P a o J FIo~.7-9 Airway pressures were measured at the operating head of the ventilator using a standard pressure transducer (Hewlett-Packard HP1280C) and a standard processor display module (Hewlett-Packard HP8205B). This system has a signal processor that uses an integrator circuit to calculate mean pressures over 12 seconds. Blood pressures were monitored through umbilical artery catheters using the same system. Both airway pressure and blood pressure monitoring systems were attached to a two channel
Significance of mean airway pressure
1 15
•/rwoy Pressure Wave Forms
I:Eratio 5oF-
~,
L
I :4
//I/
/
//
,/ i
/ i
0 l:l
(A flow)
/
/
i
/
/! 4 9
/ /
L~ . . . .
//~A ......
/
o
(insp.l:lhold)501
///. . . . . ~. . . . . ,,/
]
/
/ /
0 Iq
2 sec
ml
Fig. 1. The different airway pressure waves produced while increasing I:E ratio either by decreasing inspiratory flow rate or by employing the inspiratory time hold mechanism.
Table I. Summary of clinical data
Birth weight (gin) Gestational age (wk) Age studied (hr) Flo2 Peak inspiratory pressure (cm H20) PEEP (cm H20) Effective tidal volume (ml/kg) Rate (per minute) Pao~ (ram Hg) Paco~. (ram Hg) pH
Mean +_ SD
] Range
2,134 34 20 0.85 55
920-3,900 27-42 8-72 0.55-I.0 37-94
_+ 890 __+4 _+ 17 +_ 0.17 _ 15
6 _+ 0.9 8.7 _+ 1.3 30 _ 4 69 + 36 46 _+ 9 7.32 _+ 0.5
4-7 7-I1 25-35 24-147 37-66 7.2-7.41
recorder (Hewlett-Packard HP7402A). Statistical analysis was performed using a two-tailed t test. RESULTS Changes in mean arterial blood gases and mean blood pressures in response to changes in ventilator settings are displayed in Fig. 2. A listing of all ventilator variables, arterial blood gas measurements, blood pressure measurernents, and MAP measurements is available on request. As I:E ratios were increased from 1:4 to l : l by decreasing inspiratory flow rate, elongated triangular pressure waves were produced, and arterial oxygenation improved (P < 0.05). There was little change in Paco2 or arterial blood pressure. Returning to the baseline I:E ratio of 1"4, both MAP and Pao2/FIo2 returned to near the original baseline values.
116
o_~ rn~
Boros
The Journal of Pediatrics January 1979
60~
//
250
4o
200 200 o
~ c~ t50
}50
LL
c~
80 I00
E9 40 8'
50
c~
o
13-
I00
50
o o
I
I
]:4
I:1 (r, fl0w)
I
I
1:4
I:1 (insp.bld)
Inspiratory/ExpiratoryRatio Fig, 2. Changes in arterial blood gases and blood pressure
associated with changes in I:E ratios and airway pressure waves (Pao2/FIo=' _+ 1 SEM). Table II
Patient
MAP (cm H~O)
I:E ratio
Pressure wave
B.W.
32
1:1
Square Triangle Square Triangle Square Triangle Square Triangle
1:4
B.E.
26
1: 1 1:4
M.M.
19
m.G.
35
1:1 1:4 1:1 1:4
PEEP (cm H20)
PaoJ Fio2
4 16 7 17 5 12 5 18
187 224 257 420 186 170 222 327
Increasing I:E ratios from 1:4 to 1:1 using the respiratory time hold produced squared pressure waves and more than a twofold increase in P a o / F [ o ~ followed (P < 0.001). There was no significant change in either Paco 2 or arterial blood pressure. The P a o / F l o 2 value obtained at an I:E ratio of 1:1 using the squared airway pressure wave was significantly greater than that obtained at an I:E ratio of 1:1 using the elongated triangular wave (P < 0.001). In Fig. 3 is shown the changes in mean Pao /FIo~ values in terms of MAP alone. In all patients the P a o J F [ o~ increased a MAP increased. In all patients the best oxygenation occurred at the highest MAP and in all, highest MAP was achieved with the squared pressure wave. The significance of the shape of the airway pressure wave was examined in a separate clinical trial involving four infants ventilated at similar MAPs using both the triangular and squared wave forms. This was done by raising the PEEP of the triangular wave until an MAP
0
1
I
I
(
l
10 15 2O 25 30 MeanAirwayPressure(cmHzO)
Fig. 3. Mean changes in Pao/Flo~ associated with changes in MAP.
similar to that obtained with the squared wave was achieved (Table II). There were no significant differences in the mean Pao2/FIo2 values obtained with the two different pressure waves (P = 0.164). DISCUSSION Prolonging the inspiratory phase of the respiratory cycle during mechanical ventilation has become an accepted technique for improving arterial oxygenation. Reynolds, when restricting the peak inspiratory pressure of pressure pre-set ventilators observed that increases in I:E ratio produced plateaued or squared airway pressure waves and that significant increases in Pao2 followedP 6 Herman and Reynolds, 2 using pressure pre-set ventilators, noted that increased I:E ratios and modest amounts of PEEP acted synergistically to improve arterial oxygenation. Gains in oxygenation were thought to be due to increases in MAP, the mean pressure transmitted to the airways throughout both inspiration and expiration. Recent animal studies from our laboratory examined the relationship between I:E ratio and PEEP using volume pre-set infant ventilators.' These ventilators produced triangular pressure waves, not squared waves. We also observed that MAP was the ventilator measurement most closely related to arterial oxygenation. The present study, examining the relationship between I:E ratios and airway pressure waves, using constant tidal volume ventilators, also suggests that MAP is the best indicator of arterial oxygenation. In all cases, optimum oxygenation was achieved with the I:E ratio and pressure wave combination that produced the highest MAP. In all cases this pressure was achieved with the squared pressure wave. However, the shape of the airway pressure wave per
Volume 94 Number I
se does not appear to be particularly significant. Rather, the shape of the wave seems important only because of the changes it causes in MAP. Mean airway pressure is determined by calculating the area beneath the pressure curves of both inspiration and expiration, then dividing that area by its appropriate time. Prolonging inspiration by any technique will increase MAP. The inspiratory pressure curve with the greatest area per unit of time will therefore have the highest MAP. Increasing PEEP expands the area beneath the expiratory pressure curve and also increases MAP. Because MAP changes with any alteration of PEEP, I:E ratio, or airway pressure wave form, it is a clinically useful composite measure of all pressures transmitted to the airways by the ventilator. The relationship of MAP to the various complications of mechanical ventilation is presently under investigation.
Significance o f mean airway pressure
2.
3.
4.
5.
6. 7. 8.
REFERENCES
1. Boros SJ, Matalon SV, Ewald R, Leonard AS, and Hunt CE: The effect of independent variations in inspiratoryexpiratory ratio and end expiratory pressure during
9.
1 17
mechanical ventilation in hyaline membrane disease: The significance of mean airway pressure, J PEDIATR91:794, 1977. Herman S, and Reynolds EOR: Methods for improving oxygenation in infants mechanically ventilated for severe hyaline membrane disease, Arch Dis Child 48:612, 1973. Reynolds EOR: Effect of alterations in mechanical ventilator settings on pulmonary gas exchange in hyaline membrane disease, Arch Dis Child 46:152, 1971. BlakeAM, Durbin GM, MacNab AJ, Collins LM, Hunter NJ, and Reynolds EOR: Simplified mechanical ventilation for hyaline membrane disease, Lancet 2:1176, 1973. Reynolds EOR: Pressure wave form and settings for mechanical ventilation in severe hyaline membrane disease, Int Anesthesiol Clin 12:259, 1974. ReynoldsEOR: Management of hyaline membrane disease, Br Med Bull 31:18, 1975. HorovitzJH, Carrico CJ, and Shires T: Pulmonary response to major injury, Arch Surg 108:349, 1974. Kirby RR, Downs JB, Civetta JM, Modell JH, Dannemiller FJ, Klein EF, and Hodges M: High level positive and expiratory pressure (PEEP) in acute respiratory insufficiency, Chest 67:156, 1975. KeighleyGR: The arterial/alveolar oxygen tension ratio. An index of gas exchange applicable to varying inspired oxygen concentrations, Am Rev Resp Dis 109:142, 1974.