Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Critical Care
Published in: Critical Care 3/2007

Open Access 01-06-2007 | Research

Injurious mechanical ventilation in the normal lung causes a progressive pathologic change in dynamic alveolar mechanics

Authors: Lucio A Pavone, Scott Albert, David Carney, Louis A Gatto, Jeffrey M Halter, Gary F Nieman

Published in: Critical Care | Issue 3/2007

Login to get access

Abstract

Introduction

Acute respiratory distress syndrome causes a heterogeneous lung injury, and without protective mechanical ventilation a secondary ventilator-induced lung injury can occur. To ventilate noncompliant lung regions, high inflation pressures are required to 'pop open' the injured alveoli. The temporal impact, however, of these elevated pressures on normal alveolar mechanics (that is, the dynamic change in alveolar size and shape during ventilation) is unknown. In the present study we found that ventilating the normal lung with high peak pressure (45 cmH20) and low positive end-expiratory pressure (PEEP of 3 cmH2O) did not initially result in altered alveolar mechanics, but alveolar instability developed over time.

Methods

Anesthetized rats underwent tracheostomy, were placed on pressure control ventilation, and underwent sternotomy. Rats were then assigned to one of three ventilation strategies: control group (n = 3, Pcontrol = 14 cmH2O, PEEP = 3 cmH2O), high pressure/low PEEP group (n = 6, Pcontrol = 45 cmH2O, PEEP = 3 cmH2O), and high pressure/high PEEP group (n = 5, Pcontrol = 45 cmH2O, PEEP = 10 cmH2O). In vivo microscopic footage of subpleural alveolar stability (that is, recruitment/derecruitment) was taken at baseline and than every 15 minutes for 90 minutes following ventilator adjustments. Alveolar recruitment/derecruitment was determined by measuring the area of individual alveoli at peak inspiration (I) and end expiration (E) by computer image analysis. Alveolar recruitment/derecruitment was quantified by the percentage change in alveolar area during tidal ventilation (%I – EΔ).

Results

Alveoli were stable in the control group for the entire experiment (low %I – EΔ). Alveoli in the high pressure/low PEEP group were initially stable (low %I – EΔ), but with time alveolar recruitment/derecruitment developed. The development of alveolar instability in the high pressure/low PEEP group was associated with histologic lung injury.

Conclusion

A large change in lung volume with each breath will, in time, lead to unstable alveoli and pulmonary damage. Reducing the change in lung volume by increasing the PEEP, even with high inflation pressure, prevents alveolar instability and reduces injury. We speculate that ventilation with large changes in lung volume over time results in surfactant deactivation, which leads to alveolar instability.
Appendix
Available only for authorised users
Literature
1.
Ware LB, Matthay MA: The acute respiratory distress syndrome. N Engl J Med 2000, 342: 1334-1349. 10.1056/NEJM200005043421806CrossRefPubMed
2.
Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network N Engl J Med 2000, 342: 1301-1308. 10.1056/NEJM200005043421801
3.
Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, et al.: Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998, 338: 347-354. 10.1056/NEJM199802053380602CrossRefPubMed
4.
Corbridge TC, Wood LD, Crawford GP, Chudoba MJ, Yanos J, Sznajder JI: Adverse effects of large tidal volume and low PEEP in canine acid aspiration. Am Rev Respir Dis 1990, 142: 311-315.CrossRefPubMed
5.
Dreyfuss D, Saumon G: Role of tidal volume, FRC, and end-inspiratory volume in the development of pulmonary edema following mechanical ventilation. Am Rev Respir Dis 1993, 148: 1194-1203.CrossRefPubMed
6.
Dreyfuss D, Soler P, Basset G, Saumon G: High inflation pressure pulmonary edema. Respective effects of high airway pressure, high tidal volume, and positive end-expiratory pressure. Am Rev Respir Dis 1988, 137: 1159-1164.CrossRefPubMed
7.
Cheng KC, Zhang H, Lin CY, Slutsky AS: Ventilation with negative airway pressure induces a cytokine response in isolated mouse lung. Anesth Analg 2002, 94: 1577-1582. table of contents 10.1097/00000539-200206000-00038PubMed
8.
Schiller HJ, McCann UG 2nd, Carney DE, Gatto LA, Steinberg JM, Nieman GF: Altered alveolar mechanics in the acutely injured lung. Crit Care Med 2001, 29: 1049-1055. 10.1097/00003246-200105000-00036CrossRefPubMed
9.
Suh GY, Koh Y, Chung MP, An CH, Kim H, Jang WY, Han J, Kwon OJ: Repeated derecruitments accentuate lung injury during mechanical ventilation. Crit Care Med 2002, 30: 1848-1853. 10.1097/00003246-200208000-00029CrossRefPubMed
10.
Taskar V, John J, Evander E, Robertson B, Jonson B: Surfactant dysfunction makes lungs vulnerable to repetitive collapse and reexpansion. Am J Respir Crit Care Med 1997, 155: 313-320.CrossRefPubMed
11.
Williams EM, Viale JP, Hamilton RM, McPeak H, Sutton L, Hahn CE: Within-breath arterial PO 2 oscillations in an experimental model of acute respiratory distress syndrome. Br J Anaesth 2000, 85: 456-459. 10.1093/bja/85.2.322CrossRefPubMed
12.
Faridy EE, Permutt S, Riley RL: Effect of ventilation on surface forces in excised dogs' lungs. J Appl Physiol 1966, 21: 1453-1462.PubMed
13.
Forrest JB: The effect of hyperventilation on pulmonary surface activity. Br J Anaesth 1972, 44: 313-320. 10.1093/bja/44.4.313CrossRefPubMed
14.
Massaro GD, Massaro D: Morphologic evidence that large inflations of the lung stimulate secretion of surfactant. Am Rev Respir Dis 1983, 127: 235-236.PubMed
15.
McClenahan JB, Urtnowski A: Effect of ventilation on surfactant, and its turnover rate. J Appl Physiol 1967, 23: 215-220.PubMed
16.
Verbrugge SJ, Bohm SH, Gommers D, Zimmerman LJ, Lachmann B: Surfactant impairment after mechanical ventilation with large alveolar surface area changes and effects of positive end-expiratory pressure. Br J Anaesth 1998, 80: 360-364.CrossRefPubMed
17.
Wyszogrodski I, Kyei-Aboagye K, Taeusch HW Jr, Avery ME: Surfactant inactivation by hyperventilation: conservation by end-expiratory pressure. J Appl Physiol 1975, 38: 461-466.PubMed
18.
Halter JM, Steinberg JM, Gatto LA, Dirocco JD, Pavone LA, Schiller HJ, Albert S, Lee HM, Carney D, Nieman GF: Effect of positive end-expiratory pressure and tidal volume on lung injury induced by alveolar instability. Crit Care 2007, 11: R20. 10.1186/cc5695PubMedCentralCrossRefPubMed
19.
Nieman GF, Bredenberg CE, Clark WR, West NR: Alveolar function following surfactant deactivation. J Appl Physiol 1981, 51: 895-904.PubMed
20.
Steinberg J, Schiller HJ, Halter JM, Gatto LA, Dasilva M, Amato M, McCann UG, Nieman GF: Tidal volume increases do not affect alveolar mechanics in normal lung but cause alveolar overdistension and exacerbate alveolar instability after surfactant deactivation. Crit Care Med 2002, 30: 2675-2683. 10.1097/00003246-200212000-00011CrossRefPubMed
21.
Steinberg JM, Schiller HJ, Halter JM, Gatto LA, Lee HM, Pavone LA, Nieman GF: Alveolar instability causes early ventilator-induced lung injury independent of neutrophils. Am J Respir Crit Care Med 2004, 169: 57-63. 10.1164/rccm.200304-544OCCrossRefPubMed
22.
Veldhuizen RA, Welk B, Harbottle R, Hearn S, Nag K, Petersen N, Possmayer F: Mechanical ventilation of isolated rat lungs changes the structure and biophysical properties of surfactant. J Appl Physiol 2002, 92: 1169-1175.CrossRefPubMed
23.
Tschumperlin DJ, Margulies SS: Alveolar epithelial surface area–volume relationship in isolated rat lungs. J Appl Physiol 1999, 86: 2026-2033.PubMed
24.
Bouvet F, Dreyfuss D, Lebtahi R, Martet G, Le Guludec D, Saumon G: Noninvasive evaluation of acute capillary permeability changes during high-volume ventilation in rats with and without hypercapnic acidosis. Crit Care Med 2005, 33: 155-160. discussion 250–252 10.1097/01.CCM.0000150657.02138.29CrossRefPubMed
25.
Seeger W, Stohr G, Wolf HR, Neuhof H: Alteration of surfactant function due to protein leakage: special interaction with fibrin monomer. J Appl Physiol 1985, 58: 326-338.PubMed
26.
Veldhuizen RA, Tremblay LN, Govindarajan A, van Rozendaal BA, Haagsman HP, Slutsky AS: Pulmonary surfactant is altered during mechanical ventilation of isolated rat lung. Crit Care Med 2000, 28: 2545-2551. 10.1097/00003246-200007000-00059CrossRefPubMed
27.
Tremblay LN, Slutsky AS: Ventilator-induced lung injury: from the bench to the bedside. Intensive Care Med 2006, 32: 24-33. 10.1007/s00134-005-2817-8CrossRefPubMed
28.
Carney DE, Bredenberg CE, Schiller HJ, Picone AL, McCann UG, Gatto LA, Bailey G, Fillinger M, Nieman GF: The mechanism of lung volume change during mechanical ventilation. Am J Respir Crit Care Med 1999, 160: 1697-1702.CrossRef
29.
Macklin C: Alveoli of mamalian lung:anatomical study with clinical correlation. Proc Inst Med Chic 1950, 18.
30.
Daly BD, Parks GE, Edmonds CH, Hibbs CW, Norman JC: Dynamic alveolar mechanics as studied by videomicroscopy. Respir Physiol 1975, 24: 217-232. 10.1016/0034-5687(75)90115-2CrossRefPubMed
31.
Escolar JD, Escolar MA, Guzman J, Roques M: Pressure volume curve and alveolar recruitment/de-recruitment. A morphometric model of the respiratory cycle. Histol Histopathol 2002, 17: 383-392.PubMed
32.
Gunther A, Ruppert C, Schmidt R, Markart P, Grimminger F, Walmrath D, Seeger W: Surfactant alteration and replacement in acute respiratory distress syndrome. Respir Res 2001, 2: 353-364. 10.1186/rr86PubMedCentralCrossRefPubMed
33.
Baumgardner JE, Markstaller K, Pfeiffer B, Doebrich M, Otto CM: Effects of respiratory rate, plateau pressure, and positive end-expiratory pressure on PaO 2 oscillations after saline lavage. Am J Respir Crit Care Med 2002, 166: 1556-1562. 10.1164/rccm.200207-717OCCrossRefPubMed
34.
Syring RS, Otto CM, Spivack RE, Markstaller K, Baumgardner JE: Maintenance of end-expiratory recruitment with increased respiratory rate after saline-lavage lung injury. J Appl Physiol 2007, 102: 331-339. 10.1152/japplphysiol.00002.2006CrossRefPubMed
35.
Hotchkiss JR Jr, Blanch L, Murias G, Adams AB, Olson DA, Wangensteen OD, Leo PH, Marini JJ: Effects of decreased respiratory frequency on ventilator-induced lung injury. Am J Respir Crit Care Med 2000, 161: 463-468.CrossRefPubMed
36.
Casetti AV, Bartlett RH, Hirschl RB: Increasing inspiratory time exacerbates ventilator-induced lung injury during high-pressure/high-volume mechanical ventilation. Crit Care Med 2002, 30: 2295-2299. 10.1097/00003246-200210000-00018CrossRefPubMed
37.
Broccard AF, Hotchkiss JR, Vannay C, Markert M, Sauty A, Feihl F, Schaller MD: Protective effects of hypercapnic acidosis on ventilator-induced lung injury. Am J Respir Crit Care Med 2001, 164: 802-806.CrossRefPubMed
38.
Sinclair SE, Kregenow DA, Lamm WJ, Starr IR, Chi EY, Hlastala MP: Hypercapnic acidosis is protective in an in vivo model of ventilator-induced lung injury. Am J Respir Crit Care Med 2002, 166: 403-408. 10.1164/rccm.200112-117OCCrossRefPubMed
39.
Laffey JG, Engelberts D, Kavanagh BP: Injurious effects of hypocapnic alkalosis in the isolated lung. Am J Respir Crit Care Med 2000, 162: 399-405.CrossRefPubMed
Metadata
Title
Injurious mechanical ventilation in the normal lung causes a progressive pathologic change in dynamic alveolar mechanics
Authors
Lucio A Pavone
Scott Albert
David Carney
Louis A Gatto
Jeffrey M Halter
Gary F Nieman
Publication date
01-06-2007
Publisher
BioMed Central
Published in
Critical Care / Issue 3/2007
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc5940

Other articles of this Issue 3/2007

Critical Care 3/2007 Go to the issue

Commentary

A targeted extracorporeal therapy for endotoxemia: the time has come

Review

Bench-to-bedside review: Current evidence for extracorporeal albumin dialysis systems in liver failure

Research

Cystatin C and beta2-microglobulin: markers of glomerular filtration in critically ill children

Commentary

Kidney function assessment in the critically ill child: is it time to leave creatinine behind?

Commentary

Haemodialysis and peritoneal dialysis patients admitted to intensive care units

Commentary

Attributable mortality of Acinetobacter baumannii: no longer a controversial issue