Reprinted from the August 1994 issue of RESPIRATORY CARE [Respir Care
`1994;39(8):808–816]
`
`
`AARC Clinical Practice Guideline
`
`Neonatal Time-Triggered, Pressure-Limited,
`Time-Cycled Mechanical Ventilation
`
`TPTV 1.0 PROCEDURE:
`
`The application of time-triggered, pressure-limited, time-cycled
`mechanical ventilation (TPTV) to neonates--this Guideline does not
`address patient-triggered ventilation.
`TPTV2.0 DESCRIPTION/DEFINITION:
`
`The application of time-triggered, pressure-limited, time-cycled
`mechanical ventilation in the neonate is typically accomplished by the
`use of commercially available pressure-limited ventilators specifically
`designed for this population or of multipurpose, multimodal ventilators
`with the necessary capabilities. These ventilators permit precise
`management of ventilator settings.(1-8)
`
`Pressure-limited ventilators commonly incorporate continuous flow to
`deliver a mixture of oxygen and air. The continuous flow supplies the
`patient with a fresh gas source for spontaneous breathing.(7,9-14)
`
`Mandatory breaths are time-triggered and time-cycled, based on an
`adjustable frequency and inspiratory time. As the ventilator time-
`triggers inspiration, the exhalation valve closes, and the continuous
`flow is directed to the inspiratory limb of the patient circuit for the
`length of the inspiratory time.(7,11,12,14)
`
`Once the pressure limit has been reached, remaining flow is diverted
`to a limiting mechanism. As the ventilator cycles to expiration, the
`exhalation valve opens to ambient and the continuous flow exits the
`expiratory limb of the circuit.(7,10,14)
`
`Flow continues to enter the patient's lungs until pressure equilibrates
`or until the inspiratory time has elapsed, resulting in a decelerating
`flow pattern. Volume delivery is dependent on lung and chest-wall
`compliance and airway resistance, including the resistance of the
`endotracheal tube. As these variables change, deceleration of flow is
`
`RETIRED
`
`Ex. 2045-0001
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`

`
`altered, and the tidal volume (VT) varies.(10,11,15-22) The VT
`achieved depends on the pressure limit, gas flowrate, inspiratory time
`(tI), and positive end-expiratory pressure (PEEP). Circuit
`characteristics that affect VT include compressible volume, presence of
`condensate, and obstruction of the artificial airway.(3,4,8-
`10,18,20,23)
`
`TPTV 3.0 SETTINGS:
`
`TPTV is applied by trained personnel in acute care and subacute care
`hospitals.
`TPTV 4.0 INDICATIONS:
`
`The presence of one or more of the following conditions constitutes an
`indication for TPTV.
`4.1 Apnea (24-27)
`4.2 Respiratory or ventilatory failure, despite the use of continuous
`positive airway pressure (CPAP) and supplemental oxygen (ie, FIO2 >
`or = 0.60)(24,25,28)
`4.2.1 Respiratory acidosis with a pH < 7.20-7.25(8,25,29)
`4.2.2 PaO2 < 50 torr(8,13,25,29,30)
`4.2.3 Abnormalities on physical examination
`4.2.3.1 Increased work of breathing demonstrated by grunting, nasal
`flaring, tachypnea, and sternal and intercostal retractions(5,27,29,31)
`4.2.3.2 The presence of pale or cyanotic skin and agitation
`4.3 Alterations in neurologic status that compromise the central drive
`to breathe:
`4.3.1 Apnea of prematurity(32)
`4.3.2 Intracranial hemorrhage(33)
`4.3.3 Congenital neuromuscular disorders(34)
`4.4 Impaired respiratory function resulting in a compromised
`functional residual capacity (FRC) due to decreased lung compliance
`and/or increased airways resistance,(12,35) including but not limited
`to
`4.4.1 Respiratory distress syndrome (RDS)(1,2,28,36-39)
`4.4.2 Meconium aspiration syndrome (MAS)(40)
`4.4.3 Pneumonia(41)
`4.4.4 Bronchopulmonary dysplasia(42-44)
`4.4.5 Bronchiolitis(41)
`4.4.6 Congenital diaphragmatic hernia(45)
`4.4.7 Sepsis(41)
`4.4.8 Radiographic evidence of decreased lung volume(27)
`4.5 Impaired cardiovascular function
`4.5.1 Persistent pulmonary hypertension of the newborn
`
`RETIRED
`
`Ex. 2045-0002
`
`

`
`(PPHN)(46,47)
`4.5.2 Postresuscitation(41)
`4.5.3 Congenital heart disease(48)
`4.5.4 Shock(6)
`4.6 Postoperative state characterized by impaired ventilatory
`function(45,49)
`TPTV 5.0 CONTRAINDICATIONS:
`
`No specific contraindications for neonatal TPTV exist when indications
`are judged to be present (Section 4.0).
`TPTV 6.0 HAZARDS/COMPLICATIONS:
`
`6.1 Air leak syndromes due to barotrauma and/or volume overinflation
`(ie, volutrauma),(2,11,50-54) including
`6.1.1 Pneumothorax(16,55-59)
`6.1.2 Pneumomediastinum(55,56,58)
`6.1.3 Pneumopericardium(55)
`6.1.4 Pneumoperitoneum(55)
`6.1.5 Subcutaneous emphysema(55)
`6.1.6 Pulmonary interstitial emphysema(56,60-62)
`6.2 Chronic lung disease associated with prolonged positive pressure
`ventilation and oxygen toxicity(63,64) (eg, bronchopulmonary
`dysplasia(42,43,65-68))
`6.3 Airway complications associated with endotracheal intubation
`6.3.1 Laryngotracheobronchomalacia(69)
`6.3.2 Damage to upper airway structures(66,69,70)
`6.3.3 Malpositioning of endotracheal tube (ETT)(69,71)
`6.3.4 Partial or total obstruction of ETT with mucus(69,71,72)
`6.3.5 Kinking of ETT(69,71)
`6.3.6 Unplanned extubation(69,71,73)
`6.3.7 Air leak around uncuffed ETT
`6.3.8 Subglottic stenosis(69)
`6.3.9 Main-stem intubation(69)
`6.3.10 Pressure necrosis(74)
`6.3.11 Increased work of breathing (during spontaneous breaths) due
`to the high resistance of endotracheal tubes of small internal
`diameter(75)
`6.4 Nosocomial pulmonary infection (eg, pneumonia(76))
`6.5 Complications that occur when positive pressure applied to the
`lungs is transmitted to the cardiovascular system(77,78) or the
`cerebral vasculature resulting in
`6.5.1 Decreased venous return(77,78)
`6.5.2 Decreased cardiac output(77,78)
`6.5.3 Increased intracranial pressure leading to intraventricular
`
`RETIRED
`
`Ex. 2045-0003
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`

`
`hemorrhage(27,33,79)
`6.6 Supplemental oxygen in conjunction with TPTV may lead to an
`increased risk of retinopathy of prematurity (ROP)(80,81)
`6.7 Complications associated with endotracheal suctioning(82)
`6.8 Technical complications
`6.8.1 Ventilator failure(10,83)
`6.8.2 Ventilator circuit and/or humidifier failure(38,70) (Condensate in
`the inspiratory limb of the ventilator circuit may result in a reduction in
`VT(23,84) or inadvertent pulmonary lavage.)
`6.8.3 Ventilator alarm failure(10,38,69,83)
`6.8.4 Loss of or inadequate gas supply
`6.9 Patient-ventilator asynchrony(85,86)
`6.10 Inappropriate ventilator settings leading to
`6.10.1 auto-PEEP
`6.10.2 hypo-or hyperventilation
`6.10.3 hypo- or hyperoxemia
`6.10.4 increased work of breathing
`TPTV 7.0 LIMITATIONS OF METHOD:
`
`Rapid changes in lung compliance and airways resistance may result in
`alterations in VT delivery that may significantly alter minute ventilation
`(VE).(3,4,9,11,19-21)
`TPTV 8.0 ASSESSMENT OF NEED:
`
`Determination that valid indications are present by physical,
`radiographic, and laboratory assessment
`TPTV 9.0 ASSESSMENT OF OUTCOME:
`
`Establishment of neonatal assisted ventilation should result in
`improvement in patient condition and/or reversal of indications
`(Section 4.0):
`9.1 Reduction in work of breathing as evidenced by decreases in
`respiratory rate, severity of retractions, nasal flaring and grunting
`9.2 Radiographic evidence of improved lung volume(41)
`9.3 Subjective improvement in lung volume as indicated by increased
`chest excursion and aeration by chest auscultation(87)
`9.4 Improved gas exchange
`9.4.1 Ability to maintain a PaO2 > or = 50 torr with FIO2 <
`0.60(8,30)
`9.4.2 Ability to reverse respiratory acidosis and maintain a pH >
`7.258,30
`9.4.3 Subjective improvement as indicated by a decrease in grunting,
`nasal flaring, sternal and intercostal retraction, and respiratory
`rate(31)
`
`RETIRED
`
`Ex. 2045-0004
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`

`
`TPTV 10.0 RESOURCES:
`
`10.1 Equipment-recommended equipment based on individual patient
`need includes the following. (For a given patient, all mentioned
`equipment may not be necessary.)
`10.1.1 Commercially available continuous-flow infant ventilator
`equipped with TPTV mode or suitably equipped multipurpose,
`multimodal ventilator, low and high airway pressure alarms, high-
`pressure release-to-ambient pressure capability, loss of power and gas
`source alarms, low and high oxygen concentration alarms--alarms may
`be integral to the ventilator or an add-on.(21,38,83)
`10.1.2 Servo-regulated humidifier with low compressible volume
`chamber and preferably a continuous water source(21,38,83)
`10.1.3 Low-compliance infant ventilator circuit with heated inspiratory
`and expiratory wires compatible with the servo-regulated
`humidification system is recommended.(19,23,38,83,88,89)
`Comparable circuits that permit continual drainage of condensate may
`also be used.
`10.1.4 Endotracheal tube with associated intubation equipment or
`tracheostomy tube with associated insertion and cleaning accessories
`and supplies for securing the tube
`10.1.5 Suction source, suction catheters, and normal saline for
`instillation to ensure patency of artificial airway(82)
`10.1.6 Standby resuscitation apparatus with airway manometer and
`masks of appropriate size(83) and supplies for chest-tube insertion
`10.1.7 Continuous noninvasive monitoring of oxygenation by either
`transcutaneous monitor or pulse oximeter with high- and low-alarm
`capabilities(90,91)
`10.1.8 Continuous noninvasive monitoring of carbon dioxide by
`transcutaneous CO2 monitor with high- and low-alarm capabilities is
`also recommended(38,92) for the unstable baby requiring frequent
`ventilator changes. Measurements of end-tidal CO2 may also be useful
`in these infants.(93,94)
`10.1.9 Continuous cardiorespiratory monitoring (eg, ECG and
`respiratory rate) with high- and low-alarm capabilities(38)
`10.1.10 Appropriate and adequate compressed gas supply
`10.1.11 Graphic display of airway pressure, flow, and tidal volume
`may be useful.
`10.2 Personnel: TPTV should be applied under the direction of a
`physician by trained personnel who hold a recognized credential (eg,
`CRTT, RRT, RN) and who competently demonstrate
`10.2.1. proper use, understanding, and mastery of the technical
`aspects of management of artificial airways, mechanical ventilators,
`and humidification systems;
`
`RETIRED
`
`Ex. 2045-0005
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`

`
`10.2.2 comprehensive knowledge of ventilator management and
`understanding of neonatal airway anatomy and pulmonary
`pathophysiology;
`10.2.3 patient assessment skills, with an understanding of the
`interaction between the mechanical ventilator and the patient and
`ability to recognize and respond to adverse reactions and
`complications;
`10.2.4 knowledge and understanding of intubation equipment;
`10.2.5 ability to interpret monitored and measured blood gas
`parameters and vital signs;
`10.2.6 application of Universal Precautions;(92)
`10.2.7 proper use, understanding, and mastery of emergency
`resuscitation equipment and procedures;
`10.2.8 ability to evaluate and document results of outcome
`assessments (Section 9.0);
`10.2.9 ability to interpret chest radiographs to determine proper
`placement of artificial airways and identify complications associated
`with mechanical ventilation (eg, air leak syndromes).
`TPTV 11.0 MONITORING:
`
`11.1 Patient-ventilator system checks should be performed every 2-4
`hours and should include documentation of ventilator settings and
`patient assessments as recommended by the AARC CPG Patient-
`Ventilator System Checks (MV-SC) and AARC CPG Humidification
`during Mechanical Ventilation (HMV).(95,96)
`11.2 Oxygen and CO2 monitoring
`11.2.1 Periodic sampling of blood gas values by arterial, capillary, or
`venous route.(1,24,30) PaO2 should be kept below 80 torr in preterm
`infants to minimize the risk of ROP.(6,80,97)
`11.2.2 The unstable infant should be monitored continuously by
`transcutaneous O2 monitor or pulse oximeter.(1,90,91)
`11.2.3 The unstable infant should be monitored continuously by
`transcutaneous(90) or end-tidal CO2 monitoring.(93,94)
`11.2.4 Fractional concentration of oxygen delivered by the ventilator
`should be monitored continuously.(38)
`11.3 Continuous monitoring of cardiac activity (via electrocardiograph)
`and respiratory rate(98)
`11.4 Monitoring of blood pressure by indwelling arterial line or by
`periodic cuff measurements(24)
`11.5 Continuous monitoring of proximal airway pressures including
`peak inspiratory pressure (PIP), PEEP, and mean airway pressure
`(Paw)(1,39,99)
`11.5.1 Increases in Paw may result in improved oxygenation; however,
`Paw > 12 cm H2O has been associated with barotrauma.(8,20,41,99-
`
`RETIRED
`
`Ex. 2045-0006
`
`

`
`102)
`11.5.2 The difference between PIP and PEEP (^P) in conjunction with
`patient mechanics determines VT. As the ^P changes, VT will
`vary.(16,51,99,100)
`11.5.3 PIP should be adjusted initially to achieve adequate VT as
`reflected by chest excursion and adequate breath sounds(8,29,100)
`and/or by VT measurement.
`11.5.4 PEEP increases FRC and may improve oxygenation and
`ventilation-perfusion relationship (PEEP is typically adjusted at 4-7 cm
`H2O--levels beyond this range may result in hyperinflation, particularly
`in patients with obstructive airways disease [eg, MAS or
`bronchiolitis](5,29,35,103-105)).
`11.6 Many commercially available neonatal ventilators provide
`continuous monitoring of ventilator frequency, tI, and I:E. If only two
`of these variables are directly monitored, the third should be
`calculated (eg, the proportion of the tI for a given frequency
`determines the I:E).
`11.6.1 Lengthening tI increases Paw and should improve
`oxygenation.(1,2,13,24,41,106,107)
`11.6.2 I:E in excess of 1:1 may lead to the development of auto-PEEP
`and hyperinflation.(5,20,24,37,105,106,108)
`11.6.3 Frequencies of 30-60 per minute with shorter tI (eg, I:E of
`1:2) are commonly used in patients with RDS.(8,22,41,50,59,85,109-
`111)
`11.7 Depending on the internal diameter of the ventilator circuit,
`excessive flowrates can result in expiratory resistance that leads to
`increased work of breathing and automatic increases in
`PEEP.(17,19,89,98,86,112) Some ventilators are equipped with
`demand-flow systems that permit the use of lower baseline flowrates
`but provide the patient with additional flow as needed
`11.8 Because of the possibility of complete obstruction or kinking of
`the ETT and the inadequacy of ventilator alarms in these situations,
`continuous tidal volume monitoring via an appropriately designed
`(minimum dead space) proximal airway flow sensor is
`recommended.(98,113,114)
`11.9 Periodic physical assessment of chest excursion and breath
`sounds and for signs of increased work of breathing and
`cyanosis.(3,5,21,87)
`11.10 Periodic evaluation of chest radiographs to follow the progress
`of the disease, identify possible complications, and verify ETT
`placement(21,27,79)
`TPTV 12.0 FREQUENCY:
`
`TPTV is intended for continuous use and is discontinued when the
`
`RETIRED
`
`Ex. 2045-0007
`
`

`
`patient's clinical condition improves as indicated by results of outcome
`assessments (Section 9.0).
`TPTV 13.0 INFECTION CONTROL:
`
`No special precautions are necessary, but Universal Precautions as
`described by the Centers for Disease Control should be employed.(95)
`13.1 Ventilator circuits and humidifier chambers should not be
`changed more frequently than every 48 hours. The Clinical Practice
`Guideline: Ventilator Circuit Changes, the CDC, and, reported
`experience(114-116) suggest that use periods of > or = 5 days are
`acceptable when the humidifying device is other than an aerosol
`generator.
`13.2 External surfaces of ventilator should be cleaned according to the
`manufacturer's recommendations when the device has remained in a
`patient's room for a prolonged period, when soiled, when it has come
`in contact with potentially transmittable organisms, and after each
`patient use.
`13.3 Sterile suctioning procedures should be strictly adhered to.(82)
`Perinatal-Pediatrics Guidelines Committee:
`Lynne K Bower RRT, Chairman, Boston MA Sherry L Barnhart RRT,
`Mattoon IL Peter Betit BS RRT, Boston MA Barbara Hendon BA RRT
`RCP, Wylie TX Joanne Masi-Lynch BS RRT, Salt Lake City UT Barbara G
`Wilson MEd RRT, Durham NC
`
`2.
`
`3.
`
`REFERENCES
`1.
`Herman S, Reynolds EOR. Methods for improving oxygenation in
`infants mechanically ventilated for severe hyaline membrane
`disease. Arch Dis Child 1973;48:612-617.
`Manginello FP, Grasssi AE, Schechner S, Krauss AN, Auld PAM.
`Evaluation of methods of assisted ventilation in hyaline
`membrane disease. Arch Dis Child 1978;53:878-881.
`Carlo WA, Pacifico L, Chatburn RL, Fanaroff AA. Efficacy of
`computer-assisted management of respiratory failure in
`neonates. Pediatrics 1986;78(1):139-143.
`Chatburn RL, Carlo WA, Lough MD. Clinical algorithm for
`pressure-limited ventilation of neonates with respiratory distress
`syndrome. Respir Care 1983;28(12):1579-1586.
`Chatburn RL. Similarities and differences in the management of
`acute lung injury in neonates (IRDS) and in adults (ARDS).
`Respir Care 1988;33(7):539-553.
`Stern L. Therapy of the respiratory distress syndrome. Pediatr
`Clin North Am 1972;19(1):221-240.
`Carr DJ, Rich M, Murkowski K, Neu J. A comparative evaluation
`of three neonatal ventilators. Crit Care Med 1986;14(3):234-236.
`
`4.
`
`5.
`
`6.
`
`7.
`
`RETIRED
`
`Ex. 2045-0008
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`

`
`8.
`
`9.
`
`Carlo, WA, Martin RJ. Principles of neonatal assisted ventilation.
`Pediatr Clin North Am 1986;33(1):221-237.
`Hess D, Lind L. Nomograms for the application of the Bourns
`model BP200 as a volume-constant ventilator. Respir Care
`1980;25(2):248-250.
`10. Smith JD. Application of mechanical ventilation in acute
`respiratory failure. Respir Care 1983;28(5):579-585.
`11. Chatburn RL. Principles and practice of neonatal and pediatric
`mechanical ventilation. Respir Care 1991;36(6): 569-593.
`12. deLemos RA, Kirby RR. Early development: intermittent
`mandatory ventilation in neonatal respiratory support. Int
`Anesthesiol Clin 1980;18(2):39-51.
`13. Reynolds EOR. Pressure waveform and ventilator settings for
`mechanical ventilation in severe hyaline membrane disease. Int
`Anesthesiol Clin 1974;12(4):259-280.
`14. Kirby R, Robison E, Schulz J, deLemos RA. Continuous-flow
`ventilation as an alternative to assisted or controlled ventilation
`of infants. Anesth Analg 1972;51(6):871-875.
`15. Marini JJ, Crooke PS III, Truwit JD. Determinants and limits of
`pressure-preset ventilation: a mathematical model of pressure
`control. J Appl Physiol 1989;67(3):1081-1092.
`16. Muramatsu K, Yukitake K, Oda T. Variability of respiratory
`system compliance in mechanically ventilated infants. Pediatr
`Pulmonol 1992;12:140-145.
`17. Greenough A. The premature infant's respiratory response to
`mechanical ventilation. Early Hum Dev 1988;17:1-5.
`18. Hillman DR. Physiological aspects of intermittent positive
`pressure ventilation. Anaesth Intensive Care 1986;14(3):226-
`235.
`19. Lewis RM. Factors affecting lung volume changes during newborn
`mechanical ventilation: a bench study. Respir Care
`1992;37(10):1153-1160.
`20. Lewis RM. Automatic increases in mean airway pressure during
`mechanical ventilation. Respir Care 1982;27(6):675-681.
`21. Keuskamp DHG. Ventilation of premature and newborn infants.
`Int Anesthesiol Clin 1974;12(4):281-300.
`22. Boros SJ, Bing DR, Mammel MC, Hagen E, Gordon MJ. Using
`conventional infant ventilators at unconventional rates.
`Pediatrics 1984;74:487-492.
`23. Schena J, Monaghan EJ, Kaufman A, Thompson J, Crone RK.
`Delivered tidal volume during infant mechanical ventilation
`(abstract). Respir Care 1983;28(10): 1363.
`24. Reynolds EOR. Effect of alterations in mechanical ventilator
`settings on pulmonary gas exchange in hyaline membrane
`
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`
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`
`

`
`disease. Arch Dis Child 1971;46:152-159.
`25. Reynolds EOR. Indications for mechanical ventilation in infants
`with hyaline membrane disease. Pediatrics 1970;46(2):193-202.
`26. Sedin G. CPAP and mechanical ventilation. Int J Technol Assess
`Health Care 1991;7(Supp 1):31-40.
`27. Reynolds EOR, Taghizadeh A. Improved prognosis of infants
`mechanically ventilated for hyaline membrane disease. Arch Dis
`Child 1974;49:505-515.
`28. Meyer HBP, Griffin BE, Sedaghatian MR, Halpe PR, Daily WJR.
`Ventilatory support of the newborn infant with respiratory
`distress syndrome and respiratory failure. Int Anesthesiol Clin
`1974;12(4):81-110.
`29. Narang A, Shenoi A. Physiological principles of mechanical
`ventilation of the newborn. Indian J Pediatr 1992;59:21-27.
`30. Smith PC, Daily WJR, Fletcher G, Meyer HBP, Taylor G.
`Mechanical ventilation of newborn infants: I. the effect of rate
`and pressure on arterial oxygenation of infants with respiratory
`distress syndrome. Pediatr Res 1969;3:244-254.
`31. Harrison VC, de V Heese H, Klein M. The significance of grunting
`in hyaline membrane disease. Pediatrics 1968;41(3):549-559.
`32. Kattwinkel J, Nearman HS, Fanaroff AA, Katona PG, Klaus MH.
`Apnea of prematurity: comparative therapeutic effects of
`cutaneous stimulation and nasal continuous positive airway
`pressure. J Pediatr 1975;86(4):588-592.
`33. Allan WC, Volpe JJ. Periventricular-intraventricular hemorrhage.
`Pediatr Clin North Am 1986;36(1):47-63.
`34. Roland EH. Neuromuscular disorders in the newborn. Clin Perinat
`1989;16(2):519-547.
`35. Sivan Y, Deakers TW, Newth CJL. Functional residual capacity in
`ventilated infants and children. Pediatr Res 1990;28(5):451-454.
`36. Spahr RC, Klein AM, Brown DR, MacDonald HM, Holzman IR.
`Hyaline membrane disease: a controlled study of inspiratory to
`expiratory ratio on its management by ventilator. Am J Dis Child
`1980;134(4):373-376.
`37. Greenough A, Pool J, Greenall F, Morley C, Gamsu H.
`Comparison of different rates of artificial ventilation in preterm
`neonates with respiratory distress syndrome. Acta Paediatr
`Scand 1987;76:706-712.
`38. Hayes B. Ventilation and ventilators-an update. J Med Eng
`Technol 1988;12(5):197-218.
`39. Stark AR, Frantz ID. Respiratory distress syndrome. Pediatr Clin
`North Am 1986;33(3):533-544.
`40. Wiswell TE, Bent RC. Meconium staining and the meconium
`aspiration syndrome. Pediatr Clin North Am 1993;40(5):955-981.
`
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`
`Ex. 2045-0010
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`

`
`41. Greenough A, Roberton NRC. Neonatal ventilation. Early Hum
`Dev 1986;13:127-136.
`42. Bancalari E, Gerhardt T. Bronchopulmonary dysplasia. Pediatr
`Clin North Am 1986;33(1):1-23.
`43. Goldberg RN, Bancalari E. Bronchopulmonary dysplasia: clinical
`presentation and the role of mechanical ventilation. Respir Care
`1986;31(7):591-596.
`44. Goldberg RN, Bancalari E. Therapeutic approaches to the infant
`with bronchopulmonary dysplasia. Respir Care 1991;36(6):613-
`621.
`45. Wilson JM, Lund DP, Lillehei CW, O'Rourke PP, Vacanti JP.
`Delayed repair and preoperative ECMO does not improve survival
`in high-risk congenital diaphragmatic hernia. J Pediatr Surg
`1992;27(3):368-375.
`46. Wung J-T, James LS, Kilchevsky E, James E. Management of
`infants with severe respiratory failure and persistence of the
`fetal circulation, without hyperventilation. Pediatrics
`1985;76(4):488-494.
`47. Roberts JD Jr, Shaul PW. Advances in the treatment of persistent
`pulmonary hypertension of the newborn. Pediatr Clin North Am
`1993;40(5):983-1004.
`48. Rheuban K. The infant with congenital heart disease: guidelines
`for care in the first year of life. Clin Perinatol 1984;11(1):199-
`212.
`49. Hollinger IB. Postoperative management: ventilation. Int
`Anesthesiol Clin 1980;18(1):205-216.
`50. Oxford Region Controlled Trial of Artificial Ventilation (OCTAVE)
`Study Group. Multicentre randomised controlled trial of high
`against low frequency positive pressure ventilation. Arch Dis
`Child 1991;66(7, Spec No):770-775.
`51. Fisher JB, Mammel MC, Coleman JM, Bing DR, Boros SJ.
`Identifying lung overdistention during mechanical ventilation by
`using volume-pressure loops. Pediatr Pulmonol 1988;5:10-14.
`52. Nilsson R, Grossmann G, Robertson B. Pathogenesis of neonatal
`lung lesions induced by artificial ventilation: evidence against the
`role of barotrauma. Respiration 1980;40:218-225.
`53. Tarnow-Mordi WO, Narang A, Wilkinson AR. Lack of association
`between barotrauma and air leak in hyaline membrane disease.
`Arch Dis Child 1985;60:555-559.
`54. Primhak RA. Factors associated with pulmonary air leak in
`premature infants receiving mechanical ventilation. J Pediatr
`1983;102:764-768.
`55. Chernick V. Lung rupture in the newborn infant. Respir Care
`1986;31(7):628-633.
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`

`
`56. Thibeault DW, Lachman RS, Laul VR, Kwong MS. Pulmonary
`interstitial emphysema, pneumomediastinum, and
`pneumothorax. Am J Dis Child 1973;126:611-614.
`57. Moylan FM, Walker AM, Kramer SS, Todres ID, Shannon DC. The
`relationship of bronchopulmonary dysplasia to the occurrence of
`alveolar rupture during positive pressure ventilation. Crit Care
`Med 1978;6(3):140-142.
`58. Pollack MM, Fields AI, Holbrook PR. Pneumothorax and
`pneumomediastinum during pediatric mechanical ventilation. Crit
`Care Med 1979;7(12):536-539.
`59. Tarnow-Mordi W, Wilkinson A. Mechanical ventilation of the
`newborn (letter). Br Med J 1986;292:575.
`60. Caldwell EJ, Powell RD Jr, Mullooly JP. Interstitial emphysema: a
`study of physiologic factors involved in experimental induction of
`the lesion. Am Rev Respir Dis 1970;102:516-525.
`61. Greenough A, Dixon AK, Roberton NRC. Pulmonary interstitial
`emphysema. Arch Dis Child 1984;59:1046-1051.
`62. Plenat F, Vert P, Didier F, Andre M. Pulmonary interstitial
`emphysema. Clin Perinatol 1978;5(2):351-375.
`63. Cooke RWI. Factors associated with chronic lung disease in
`preterm infants. Arch Dis Child 1991;66(7, Spec No):776-779.
`64. Stocks J, Godfrey S. The role of artificial ventilation, oxygen, and
`CPAP in the pathogenesis of lung damage in neonates:
`assessment by serial measurements of lung function. Pediatrics
`1976;57(3):352-362.
`65. Taghizadeh A, Reynolds EOR. Pathogenesis of bronchopulmonary
`dysplasia following hyaline membrane disease. Am J Pathol
`1976;82(2):241-264.
`66. Riedel F. Long term effects of artificial ventilation in neonates.
`Acta Paediatr Scand 1987;76:24-29.
`67. Avery ME, Tooley WH, Keller JB, Hurd SS, Bryan MH, Cotton RB,
`et al. Is chronic lung disease in low birth weight infants
`preventable? A survey of eight centers. Pediatrics
`1987;79(1):26-30.
`68. Wung J-T, Koons AH, Driscoll JM Jr, James LS. Changing
`incidence of bronchopulmonary dysplasia. J Pediatr 1979;95(5,
`Part 2):845-847.
`69. Truog WE. Complications of mechanical ventilation and airway
`control in the neonate. Respir Care 1986;31(6): 498-505.
`70. Loochtan AM, Loochtan RM. Damage to neonatal oral structures:
`effects of laryngoscopy and intubation. Respir Care
`1989;34(10):879-888.
`71. Benjamin PK, Thompson JE, O'Rourke PP. Complications of
`mechanical ventilation in a children's hospital multidisciplinary
`
`RETIRED
`
`Ex. 2045-0012
`
`

`
`intensive care unit. Respir Care 1990;35(9):873-878.
`72. Redding GJ, Fan L, Cotton EK, Brooks JG. Partial obstruction of
`endotracheal tubes in children: incidence, etiology, significance.
`Crit Care Med 1979;7(5):227-231.
`73. Kallstrom TJ, Salyer J. The incidence of accidental extubations in
`a neonatal intensive care unit (abstract). Respir Care
`1989;34(11):1006.
`74. Benjamin PK, Thompson JE, Arnold JH. ETT pressure necrosis in
`a pediatric cardiac intensive care unit (CICU) (abstract). Respir
`Care 1992;37(11):1331.
`75. Farstad T, Bratild D. Effects of endotracheal tube size and
`ventilator settings on the mechanics of a test system during
`intermittent flow ventilation. Pediatr Pulmonol 1991;11:15-21.
`76. Sottile FD, Marrie TJ, Prough DS, Hobgood CD, Gower DJ, Webb
`LX, Costerton JW, Gristina AG. Nosocomial pulmonary infection:
`possible etiologic significance of bacterial adhesion to
`endotracheal tubes. Crit Care Med 1986;14(4):265-270.
`77. MacDonnell KF. Physiologic consequences of mechanical
`ventilation. Compr Ther 1977;3(12):49-58.
`78. Douglas ME, Downs JB. Cardiopulmonary effects of intermittent
`mandatory ventilation. Int Anesthesiol Clin 1980;18(2):97-121.
`79. Peabody JL. Mechanical ventilation of the newborn: good
`news . . . bad news. Crit Care Med 1981;9(10):710-713.
`80. Avery GB, Glass P. Retinopathy of prematurity: what causes it?
`Clin Perinatol 1988;15(4):917-928.
`81. Reisner SH, Amir J, Shohat M, Krikler R, Nissenkorn I, Ben-Sira I.
`Retinopathy of prematurity: incidence and treatment. Arch Dis
`Child 1985;60:698-701.
`82. American Association for Respiratory Care. Clinical practice
`guideline: endotracheal suctioning of mechanically ventilated
`adults and children with artificial airways. Respir Care
`1993;38(5):500-504.
`83. Lawrence JC. Breathing system gas pressure monitoring and
`venting, ventilator monitors and alarms. Anaesth Intensive Care
`1988;16(1):38-40.
`84. Schachter EN, Lehnert BE, Specht W. Pressure-time relationships
`of pressure-limited neonatal ventilators. Crit Care Med
`1983;11(3):177-181.
`85. Greenough A, Greenall F, Gamsu H. Synchronous respiration:
`which ventilator rate is best? Acta Paediatr Scand 1987;76:713-
`718.
`86. Field D, Milner AD, Hopkin IE. Manipulation of ventilator settings
`to prevent active expiration against positive pressure inflation.
`Arch Dis Child 1985;60:1036-1040.
`
`RETIRED
`
`Ex. 2045-0013
`
`

`
`87. Goldstein B, Catlin EA, Vetere JM, Arguin LJ. The role of in-line
`manometers in minimizing peak and mean airway pressure
`during the hand-regulated ventilation of newborn infants. Respir
`Care 1989;34(1):23-27.
`88. Sullivan L, Strong K, Trahey J, Hess D. Relative humidity
`delivered by a neonatal heated wire circuit (abstract). Respir
`Care 1993;38(11):1249.
`89. Scott LR, Benson MS, Pierson DJ. Effect of inspiratory flowrate
`and circuit compressible volume on auto-PEEP during mechanical
`ventilation. Respir Care 1986;31(11): 1075-1079.
`90. Severinghaus JW. Transcutaneous blood gas analysis. Respir
`Care 1982;27(2):152-159.
`91. Hay Jr WW, Brockway JM, Eyzaguirre M. Neonatal pulse
`oximetry: accuracy and reliability. Pediatrics 1989;83(5):717-
`722.
`92. Centers for Disease Control. Update: Universal Precautions for
`prevention of transmission of human immunodeficiency virus,
`hepatitis B virus, and other bloodborne pathogens in health care
`settings. MMWR 1988;37:377-382,387-388.
`93. Watkins AMC, Weindling AM. Monitoring of end tidal CO2 in
`neonatal intensive care. Arch Dis Child 1987;62:837-859.
`94. Beatty B, Roberts J. End-tidal CO2 measurements in intubated
`neonates weighing less than 2000 grams (abstract). Respir Care
`1992;37(11):1341.
`95. American Association for Respiratory Care. Clinical practice
`guideline: humidification during mechanical ventilation. Respir
`Care 1992;37(8):887-890.
`96. American Association for Respiratory Care. Clinical practice
`guideline: patient-ventilator system checks. Respir Care
`1992;37(8):882-886.
`97. American Association for Respiratory Care. Clinical practice
`guideline: oxygen therapy in the acute care hospital. Respir Care
`1991;36(12):1410-1413.
`98. McCann EM, Goldman SL, Brady JP. Pulmonary function in the
`sick newborn infant. Pediatr Res 1987;21(4): 313-325.
`99. Stewart AR, Finer NN, Peters KL. Effects of alterations of
`inspiratory and expiratory pressures and inspiratory/expiratory
`ratios on mean airway pressure, blood gases, and intracranial
`pressure. Pediarics 1981;67(4):474-481.
`100. Ciszek TA, Modanlou HD, Owings D, Nelson P. Mean airway
`pressure-significance during mechanical ventilation in neonates.
`J Pediatr 1981;99(1):121-126.
`101. Pesenti A, Marcolin R, Prato P, Borelli M, Riboni A, Gattinoni L.
`Mean airway pressure vs positive end-expiratory pressure during
`
`RETIRED
`
`Ex. 2045-0014
`
`

`
`mechanical ventilation. Crit Care Med 1985;13(1):34-37.
`102. Boros SJ, Matalon SV, Ewald R, Leonard AS, Hunt CE. The effect
`of independent variations in inspiratory-expiratory ratio and end
`expiratory pressure during mechanical ventilation in hyaline
`membrane disease: the significance of mean airway pressure. J
`Pediatr 1977;91(5): 794-798.
`103. Simbruner G. Inadvertent positive end-expiratory pressure in
`mechanically ventilated newborn infants: detection and effect on
`lung mechanics and gas exchange. J Pediatr 1986;108:589-595.
`104. Pierson DJ. Alveolar rupture during mechanical ventilation: role
`of PEEP, peak airway pressure, and distending volume. Respir
`Care 1988;33(6):472-484.
`105. Ramsden CA, Reynolds EOR. Ventilator settings for newborn
`infants. Arch Dis Child 1987;62:529-538.
`106. Boros SJ, Campbell K. A comparison of the effects of high
`frequency-low tidal volume and low frequency-high tidal volume
`mechanical ventilation. J Pediatr 1980;97(1):108-112.
`107. Hird M, Greenough A. Inflation time in mechanical ventilation of
`preterm neonates. Eur J Pediatr 1991;150(6):440-443