Download PDF
Am J Perinatol 2003; 20(8): 453-464
DOI: 10.1055/s-2003-45388
ORIGINAL ARTICLE

Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Low-Birth-Weight Neonates Exhibit a Physiological Set-Point to Regulate CO2: An Untapped Potential to Minimize Volutrauma-Associated Lung Injury

Ravi Mishra1 , Sergio G. Golombek1 , Susan R. Ramirez-Tolentino2 , Santanu Das2 , Edmund F. La Gamma1
  • 1The Regional Neonatal Center, New York Medical College-Westchester Medical Center, Valhalla, New York
  • 2The Division of Newborn Medicine, Department of Pediatrics, State University of New York at Stony Brook, New York
Further Information

Publication History

Publication Date:
02 January 2004 (online)

    Permissions and Reprints

ABSTRACT

The objective of this article is to determine whether low-birth-weight (LBW) infants have the capacity to modulate minute ventilation to achieve a CO2 set-point within ranges acceptable to clinicians during a procedure designed to identify the best dynamic compliance loops. By using dynamic flow-loop mechanics, we performed a prospective stepwise reduction of tidal volume (by reduction of peak inspiratory pressure, keeping end-expiratory pressure constant), in a group of LBW infants to identify the steepest slope of the dynamic flow-loop. We used flow-synchronized, assist-control mechanical ventilation with termination sensitivity set at 5%. Vital signs and blood gases were assessed every 15 minutes at each stepped-pressure change during the first hour after enrollment and after 12 hours, to evaluate oxygenation and ventilation. Peak inspiratory pressure (PIP) was selected at the lowest level that achieved target range blood gases. The acute reduction of PIP and the resulting lower tidal volume was initially associated with an increase in the spontaneous respiratory rate in the first hour that also was associated with a significant decrease in patient-selected inspiration time. After 12 hours, the spontaneous respiratory rate returned to baseline; the peak PaCO2 was 43.8 ± 2.03 (mean ± SEM). LBW infants have the capacity to alter respiratory rate to change minute ventilation in response to a reduction of tidal volume created by lowering the PIP. Using this model of endogenous CO2 challenge in ventilated infants, we conclude that LBW neonates have the capacity to select a CO2 set-point. This approach suggests an important avenue through which a clinician can minimize volutrauma through a reduction of PIP and use of expiratory trigger to limit excessive PIP and an overall lower mean airway pressure.

KEYWORDS

Very-low-birth-weight - physiological set-point - CO2 sensitivity - permissive hypercapnia - respiratory distress syndrome

REFERENCES

  • 1 Dreyfuss D, Saumon G. Barotrauma is volutrauma, but which volume is the one responsible?.  Intensive Care Med . 1992;  18 139-141
    CrossrefPubMedGoogle Scholar
  • 2 Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons from experimental studies.  Am J Respir Crit Care Med . 1998;  157 294-323
    CrossrefPubMedGoogle Scholar
  • 3 Parker J C, Hernandez L A, Peevy K J. Mechanisms of ventilator-induced lung injury.  Crit Care Med . 1993;  21 131-143
    CrossrefPubMedGoogle Scholar
  • 4 Slutsky A S. Lung injury caused by mechanical ventilation.  Chest . 1999;  116 (suppl 1) 9S-15S
    CrossrefPubMedGoogle Scholar
  • 5 Tremblay L N, Slutsky A S. Ventilator-induced injury: from barotrauma to biotrauma.  Proc Assoc Am Physicians . 1998;  110 482-488
    PubMedGoogle Scholar
  • 6 Muscedere J G, Mullen J B, Gan K, Slutsky A S. Tidal ventilation at low airway pressures can augment lung injury.  Am J Respir Crit Care Med . 1994;  149 1327-1334
    PubMedGoogle Scholar
  • 7 Clark R H, Gerstmann D R, Jobe A H, Moffitt S T, Slutsky A S, Yoder B A. Lung injury in neonates: causes, strategies for prevention, and long-term consequences.  J Pediatr . 2001;  139 478-486
    CrossrefPubMedGoogle Scholar
  • 8 Ranieri V M, Suter P M, Tortorella C. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial.  JAMA . 1999;  282 54-61
    CrossrefPubMedGoogle Scholar
  • 9 Chiumello D, Pristine G, Slutsky A S. Mechanical ventilation affects local and systemic cytokines in an animal model of acute respiratory distress syndrome.  Am J Respir Crit Care Med . 1999;  160 109-116
    PubMedGoogle Scholar
  • 10 Slutsky A S, Tremblay L N. Multiple system organ failure. Is mechanical ventilation a contributing factor?.  Am J Respir Crit Care Med . 1998;  157(6 Pt 1) 1721-1725
    PubMedGoogle Scholar
  • 11 Amato M B, Barbas C S, Medeiros D M. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome.  N Engl J Med . 1998;  338 347-354
    CrossrefPubMedGoogle Scholar
  • 12 Laffey J G, Tanaka M, Engelberts D. Therapeutic hypercapnia reduces pulmonary and systemic injury following in vivo lung reperfusion.  Am J Respir Crit Care Med . 2000;  162 2287-2294
    PubMedGoogle Scholar
  • 13 The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.  N Engl J Med . 2000;  342 1301-1308
    CrossrefPubMedGoogle Scholar
  • 14 Vannucci R C, Towfighi J, Heitjan D F, Brucklacher R M. Carbon dioxide protects the perinatal brain from hypoxic-ischemic damage: an experimental study in the immature rat.  Pediatrics . 1995;  95 868-874
    PubMedGoogle Scholar
  • 15 Mariani G, Cifuentes J, Carlo W A. Randomized trial of permissive hypercapnia in preterm infants.  Pediatrics . 1999;  104(5 Pt 1) 1082-1088
    CrossrefPubMedGoogle Scholar
  • 16 Lee K S, Dunn M S, Fenwick M, Shennan A T. A comparison of underwater bubble continuous positive airway pressure with ventilator-derived continuous positive airway pressure in premature neonates ready for extubation.  Biol Neonate . 1998;  73 69-75
    CrossrefPubMedGoogle Scholar
  • 17 Van Marter J L, Allred E N, Pagano M. Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease?.  <~>The Neonatology Committee for the Developmental Network. Pediatrics . 2000;  105 1194-1201
    CrossrefPubMedGoogle Scholar
  • 18 Yoder B A, Siler-Khodr T, Winter V T, Coalson J J. High-frequency oscillatory ventilation: effects on lung function, mechanics, and airway cytokines in the immature baboon model for neonatal chronic lung disease.  Am J Respir Crit Care Med . 2000;  162 1867-1876
    PubMedGoogle Scholar
  • 19 Durand D J, Asselin J M, Hudak M L. Early high-frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation in very low birth weight infants: a pilot study of two ventilation protocols.  J Perinatol . 2001;  21 221-229
    CrossrefPubMedGoogle Scholar
  • 20 Imai Y, Nakagawa S, Ito Y, Kawano T, Slutsky A S, Miyasaka K. Comparison of lung protection strategies using conventional and high-frequency oscillatory ventilation.  J Appl Physiol . 2001;  91 1836-1844
    PubMedGoogle Scholar
  • 21 Gerstmann D R, Wood K, Miller A. Childhood outcome after early high-frequency oscillatory ventilation for neonatal respiratory distress syndrome.  Pediatrics . 2001;  108 617-623
    CrossrefPubMedGoogle Scholar
  • 22 Donn S M, Nicks J J, Becker M A. Flow-synchronized ventilation of preterm infants with respiratory distress syndrome.  J Perinatol . 1994;  14 90-94
    PubMedGoogle Scholar
  • 23 Donn S M, Sinha S K. Controversies in patient-triggered ventilation.  Clin Perinatol . 1998;  25 49-61
    PubMedGoogle Scholar
  • 24 Okumura A, Hayakawa F, Kato T. Hypocarbia in preterm infants with periventricular leukomalacia: the relation between hypocarbia and mechanical ventilation.  Pediatrics . 2001;  107 469-475
    CrossrefPubMedGoogle Scholar
  • 25 Dammann O, Allred E N, Kuban K C. Hypocarbia during the first 24 postnatal hours and white matter echolucencies in newborns. 
    PubMedGoogle Scholar
  • 26 Laffey J G, Engelberts D, Kavanagh B P. Injurious effects of hypocapnic alkalosis in the isolated lung.  Am J Respir Crit Care Med . 2000;  162(2 Pt 1) 399-405
    PubMedGoogle Scholar
  • 27 Rigatto H. Maturation of breathing.  Clin Perinatol . 1992;  19 739-756
    PubMedGoogle Scholar
  • 28 Moriette G, Van Reempts P, Moore M, Cates D, Rigatto H. The effect of rebreathing CO2 on ventilation and diaphragmatic electromyography in newborn infants.  Respir Physiol . 1985;  62 387-397
    CrossrefPubMedGoogle Scholar
  • 29 Rigatto H, Kwiatkowski K A, Hasan S U, Cates D B. The ventilatory response to endogenous CO2 in preterm infants.  Am Rev Respir Dis . 1991;  143 101-104
    PubMedGoogle Scholar
  • 30 Rigatto H, Brady J P. Periodic breathing and apnea in preterm infants. I. Evidence for hypoventilation possibly due to central respiratory depression.  Pediatrics . 1972;  50 202-218
    PubMedGoogle Scholar
  • 31 Miller M J, DiFiore J M, Strohl K P, Carlo W A, Martin R J. Effects of CO2 rebreathing on pulmonary mechanics in premature infants.  J Appl Physiol . 1991;  70 2582-2586
    PubMedGoogle Scholar
  • 32 Michna J, Jobe A H, Ikegami M. Positive end-expiratory pressure preserves surfactant function in preterm lambs.  Am J Respir Crit Care Med . 1999;  160 634-639
    PubMedGoogle Scholar
  • 33 Campbell D E, Fleischman A R. Limits of viability: dilemmas, decisions, and decision makers.  Am J Perinatol . 2001;  18 117-128
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Jobe A H, Ikegami M. Lung development and function in preterm infants in the surfactant treatment era.  Annu Rev Physiol . 2000;  62 825-846
    CrossrefPubMedGoogle Scholar
  • 35 Niu J O, Munshi U K, Siddiq M M, Parton L A. Early increase in endothelin-1 in tracheal aspirates of preterm infants: correlation with bronchopulmonary dysplasia.  J Pediatr . 1998;  132 965-970
    PubMedGoogle Scholar
  • 36 Fencl V, Miller T B, Pappenheimer J R. Studies on the respiratory response to disturbances of acid-base balance, with deductions concerning the ionic composition of cerebral interstitial fluid.  Am J Physiol . 1966;  210 459-472
    PubMedGoogle Scholar
  • 37 Lumb A, Nunn J F. Nunn's Applied Respiratory Physiology. 5th ed. Oxford, Boston: Butterworth-Heinemann 2000 : 100-101
    Google Scholar
  • 38 Siesjo B K. Quantification of pH regulation in hypercapnia and hypocapnia.  Scand J Clin Lab Invest . 1971;  28 113-119
    PubMedGoogle Scholar
  • 39 Robbins P A. Hypoxic ventilatory decline: site of action.  J Appl Physiol . 1995;  79 373-374
    PubMedGoogle Scholar
  • 40 Sinha S K, Donn S M. Manual of Neonatal Respiratory Care. 1st ed. Armonk, NY: Futura Publishing Co, Inc; 2000: 65-66
    Google Scholar
  • 41 Dimitriou G, Greenough A, Laubscher B, Yamaguchi N. Comparison of airway pressure-triggered and airflow-triggered ventilation in very immature infants.  Acta Paediatr . 1998;  87 1256-1260
    CrossrefPubMedGoogle Scholar
  • 42 Miller R D, Cucchiara R F. Anesthesia. Vol. 2. Philadelphia: Churchill Livingstone; 2000: 587-588
    Google Scholar
  • 43 Polin R A, Fox W W. Fetal and Neonatal Physiology.  2nd ed. Philadelphia: Saunders 1998: 1169-1170
    Google Scholar
      >