HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tönz, M. Articles by Kaiser, G. Search for Related Content PubMed PubMed Citation Articles by Tönz, M. Articles by Kaiser, G.

Ann Thorac Surg 1998;66:542-546
© 1998 The Society of Thoracic Surgeons

---

Original articles: cardiovascular

Pulmonary function after one-lung ventilation in newborns: the basis for neonatal thoracoscopy

^a Department of Pediatric Surgery, University Children’s Hospital, Bern, Switzerland
^b Department of Pediatric Intensive Care, University Children’s Hospital, Bern, Switzerland
^c Department of Surgical Research Unit, University Children’s Hospital, Bern, Switzerland

Accepted for publication March 30, 1998.

Address reprint requests to Dr Tönz, Department of Pediatric Surgery, University Children’s Hospital, 3010 Bern, Switzerland

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. To maintain good exposure during major video-assisted thoracic surgery it is necessary to deflate completely the ipsilateral lung. However, little is known about the effects of one-lung ventilation (OLV) on pulmonary function in newborn patients.

Methods. Ten neonatal domestic pigs with a mean age of 6 ± 0.6 days were intubated and ventilated in pressure-controlled mode (inspired oxygen fraction = 1.0). One-lung ventilation was maintained for 120 minutes. Serial measurements of hemodynamics and gas exchange were done before, during, and until 90 minutes after OLV. Pulmonary function testing was performed before and after OLV for each lung separately.

Results. With the inspired oxygen fraction set at 1.0, arterial oxygen saturation remained stable at 100% during OLV. Venous admixture and alveolar–arterial oxygen tension gradient increased slightly from the baseline value of 2.6% ± 0.3% to 3.8% ± 0.3% during OLV (mean ± standard error of the mean; p = 0.02), and from 358 ± 28 to 407 ± 18 mm Hg (not significant), respectively. Both values returned to baseline during the subsequent ventilation of both lungs. Static compliance and resistance of the ventilated lung did not change. Compliance of the collapsed lung decreased after reexpansion from 0.42 ± 0.07 to 0.29 ± 0.06 mL · cm H₂O^-1 · kg^-1, p = 0.008). Resistance remained unchanged (0.22 ± 0.02 versus 0.25 ± 0.05 cm H₂O · L^-1 · s^-1; not significant).

Conclusions. There were only minor effects on pulmonary function during and after OLV in the neonatal piglet. Alterations in gas exchange during OLV were minimal. Prolonged collapse of the lung with subsequent reexpansion was associated with a slight decrease in compliance, indicating some mild lung injury.

	Introduction

Top Abstract Introduction Material and methods Results Comment References

 
Minimally invasive thoracic surgery has gained wide acceptance in the last few years. Broad clinical experience, however, exists with adult patients only. To offer the advantages of this new technique even to our youngest patients, newborn infants, we have to improve our basic knowledge about the implication of this technique for this group of patients. For major video-assisted thoracic surgery, in contrast to the already successfully performed thoracoscopic clipping of patent ductus arteriosus [1], it is necessary to deflate completely the ipsilateral lung. One-lung ventilation (OLV) has several effects on pulmonary hemodynamics and gas exchange [2]. In adults and children these effects are generally limited [3]. In a preliminary study in newborns we demonstrated that OLV was reasonably well tolerated in newborn piglets with regard to hemodynamics and gas exchange [4]. The effects of prolonged total lung collapse on lung function in the newborn, however, remains unclear. There is some evidence that atelectasis and reexpansion of the lung may be associated with a degree of acute lung injury [5, 6]. The aim of this study was to evaluate these effects in an animal model using newborn domestic pigs.

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

 
Preparation
Ten newborn domestic pigs with an age of 6 ± 0.6 days (mean ± standard error of the mean) and a body weight of 2.4 ± 0.2 kg were premedicated with intramuscular ketamine sodium (20 mg/kg) and xylazine (2 mg/kg). After induction of anesthesia with intravenous atropine (0.04 mg/kg), azaperone (3 mg/kg), and metomidate (10 mg/kg), the trachea was intubated and ventilation started in a pressure-controlled mode with a fractional inspired concentration of oxygen (FiO₂) of 1.0, a peak inspiratory pressure of 18 cm H₂O, and a respiratory rate of 20/min, adjusted to maintain arterial carbon dioxide tension within normal limits. Positive end-expiratory pressure was set at 4 cm H₂O. Anesthesia was maintained with intravenous fentanyl (5 µg/kg per hour) and metomidate (10 mg/kg per hour). Neuromuscular blockade was achieved by administration of vecuronium bromide if necessary. Throughout the experiment, normal saline was infused at a rate of 4 mL · kg^-1 · min^-1, and volume therapy was performed by infusion of hydroxyethylstarch solution. Temperature was maintained at 37° to 38°C using a heating pad. The study was approved by the institutional ethical comitee, and the animals were cared for according to the principles of laboratory animal care formulated by the Swiss Academy of Science.

An arterial catheter was placed in the abdominal aorta through the right femoral artery for systemic arterial pressure measurements and arterial blood sampling, and a venous catheter was advanced into the inferior vena cava through the right femoral vein for measurements of the central venous pressure. A tracheotomy was performed to replace the oral endotracheal tube by a short 4.5-mm endotracheal tube with its tip in the proximal third of the trachea, to assure good ventilation of the right upper lobe. After left thoracotomy, a pulmonary artery catheter was placed for measurements of pulmonary artery pressure and for mixed venous blood sampling, and the ductus arteriosus was ligated. After mobilization of the left mainstem bronchus, a 2.5-mm endobronchial tube was inserted through a second tracheotomy and positioned in the left mainstem bronchus. A ligature around the left mainstem bronchus was set for airtight closure. The endotracheal and endobronchial tubes were connected with a Y-piece. The chest was partially closed to minimize changes in compliance of the respiratory system. The completeness of lung collapse was controlled by thoracoscopy. Reexpansion of the collapsed lung was achieved by gentle manual ventilation under direct and thoracoscopic vision after the animal was returned to the supine position.

Measurements
Central venous, pulmonary artery, and systemic arterial pressures were continuously recorded (Hellige GmbH, Freiburg im Breisgau, Germany). Blood samples were obtained from the femoral artery and pulmonary artery catheters for blood gas analysis (ABL; Radiometer, Copenhagen, Denmark). Venous admixture and alveolar–arterial oxygen tension gradient were calculated by standard formulas with the FiO₂ set at 1.0, assuming full equilibration between alveolar and capillary oxygen tension, and alveolar carbon dioxide tension equal to arterial carbon dioxide tension. The static compliance (CRS) and resistance (RRS) of the total respiratory system were measured by the single-breath occlusion method, using a SensorMedics 2600 Pediatric Pulmonary Cart (SensorMedics Co, Yorba Linda, CA) [7]. With this technique the airway was occluded by a shutter valve for 100 ms at the end of a mechanical breath, and alveolar pressure was recorded. After release of the shutter valve the animal was allowed to exhale through a pneumotachograph to ambient air at atmospheric pressure, resulting in passive expiratory flow and integrated volume measurements. For each value of CRS and RRS at least three measurements not differing more than 10% were averaged. For interindividual comparison CRS was normalized for body weight (CRS/kg). Lung function measurements were performed separately for each lung. During the measurements the contralateral lung was ventilated manually in a synchronous mode.

Protocol
Baseline measurements were completed after a 30-minute equilibration period in supine position. Thereafter, the left bronchial tube was disconnected, resulting in total collapse of the left lung. The animal was placed in a right lateral decubitus position. One-lung ventilation was maintained for 120 minutes with serial measurement of hemodynamics and blood gas analyses. After this period, the animal was returned to a supine position and serial measurements were performed during 90 minutes. Lung function was assessed before OLV and 90 minutes after reexpansion in the supine position.

Statistics
Values are reported as mean ± standard error of the mean. Data were analyzed by means of a statistical software program (StatView 4.0; Abacus Concepts Inc, Berkeley, CA). Hemodynamic and gas exchange data during and after OLV were pooled for each animal and time period, and differences between time periods were assessed by unpaired Student’s t test. The significance of differences for comparing changes in lung function were analyzed with Student’s t test for paired data. Differences were considered to be significant at a probability level of p less than 0.05.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
Hemodynamics and gas exchange
Throughout the time of the experiment, there was a constant increase in heart rate with a concomitant decrease in systemic arterial pressure, independent of the experimental protocol and despite the fact that fluid administration was adjusted to maintain filling pressures at a constant level (Table 1). Mixed venous oxygen saturation did not change, indicating that there were no gross changes in cardiac output (also in accordance to limited personal data with pulmonary artery flow measurements in preliminary experiments). On institution of OLV, pulmonary artery pressure increased slightly from 16 ± 1 to 18 ± 0 mm Hg (p = 0.005) and remained elevated after reexpansion of the left lung. With the FiO₂ set at 1.0, arterial oxygen saturation remained stable at 100% during OLV. Venous admixture and alveolar–arterial oxygen tension gradient increased slightly from 2.6% ± 0.3% to 3.8% ± 0.3% (p = 0.02) and from 358 ± 28 to 407 ± 18 mm Hg (not significant [NS]), respectively. Both values returned to baseline levels during the subsequent ventilation of both lungs.

View larger version (20K): [in this window] [in a new window]   Fig 1. Pulmonary function parameters before and after one-lung ventilation (n = 10). The difference of baseline values of resistance between right and left lung are explained by the different diameters of the intratracheal and intrabronchial tubes, respectively. (circles = right, ventilated lung; CRS = compliance; Insp Vol = inspiratory volume; RRS = resistance; squares = left, collapsed lung; *p < 0.05 before versus after one-lung ventilation.)

	Comment

Top Abstract Introduction Material and methods Results Comment References

Hemodynamics and gas exchange
There are several factors that may interfere with an effective transport of oxygen from the atmosphere to the cells of the body during OLV. Blood from alveoli that are underventilated in relation to perfusion results in the admixture of venous blood to the arterial blood. Hypoxic pulmonary vasoconstriction, as a mechanism of pulmonary autoregulation, attenuates this development of hypoxemia by actively reducing perfusion of deoxygenated blood through nonventilated segments of the lung [2]. Oxygen uptake occurs as the blood moves through the pulmonary capillaries. Oxygenation of mixed venous blood is influenced to a large extent by the time it takes for oxygen to combine chemically with hemoglobin [8]. In the neonate, cardiac output is higher than in the adult on a per kilogram basis, ie, the circulation time is reduced. Therefore, the time available for gas exchange is sharply reduced to about 0.21 seconds (normal adult value, 0.75 seconds [9]), which has been reported to be the minimal time required for complete O₂ capillary equilibrium in neonates [10]. This calculated value would predict that normal reserves in pulmonary function are minimal in the newborn, and that only slight changes in membrane diffusion capacity or a decrease in pulmonary capillary transit time would adversely affect gas exchange [10]. In fact, Escourrou and colleagues [11] demonstrated an impaired oxygen uptake when cardiac output was increased twofold in neonatal piglets.

In our study we calculated venous admixture and alveolar–arterial oxygen tension gradient before, during, and after OLV. Venous admixture and alveolar–arterial oxygen tension gradient depend on the degree of oxygen uptake limitation, anatomic right-to-left shunt, and distribution of the ventilation–perfusion ratio. During OLV, we observed a minimal increase in venous admixture and alveolar–arterial tension gradient. This means that, in neonatal piglets, hypoxic pulmonary vasoconstriction and the collapse of the pulmonary capillary bed provide for total, or near total, cessation of pulmonary blood flow in the nonventilated lung, resulting in a more or less exclusive perfusion of the ventilated lung. Furthermore, functional reserve of the neonatal lung with regard to oxygen uptake capacity seems to be enough to guarantee sufficient oxygen transfer, even if lung perfusion is increased to nearly twice the baseline value.

Lung function
One-lung ventilation with an open thorax results in a total collapse of the nonventilated lung. To assess the effects of atelectasis and reexpansion on lung function we measured compliance, resistance, and alveolar–arterial oxygen tension gradient before and after OLV. In the atelectatic lung, we observed no changes in resistance, but a slight decrease in compliance after OLV. There are several mechanisms that might be responsible for the impaired compliance after transitory collapse of the lung. Probably the most relevant ones are pulmonary edema and surfactant dysfunction.

In fact, pulmonary edema after reexpansion of the atelectatic lung has been described by several authors [6, 12, 13]. It is thought to be the consequence of damage to the pulmonary capillary membrane with an increase in permeability, either because of direct anoxic injury or mediated by an inflammatory response after reexpansion and reperfusion [6, 13, 14]. It is difficult to assess the contribution of increased interstitial or even intraalveolar fluid to the decreased compliance after OLV in our experimental setting. Because alveolar–arterial oxygen tension gradient, a good measure of membrane diffusion capacity, did not increase after OLV, we can exclude relevant pulmonary edema. This is in accordance with the results of Zollinger and associates [15], who found no changes in extravascular lung water after 2 hours of OLV in juvenile pigs.

In 1963, Sutnick and Soloff [16] first demonstrated that surfactant activity in the atelectatic lung was markedly lower than that of normal lung. This finding were confirmed by other studies [12, 17]. However, until now, there is little knowledge about the pathogenesis of surfactant dysfunction in the atelectatic lung. It might be of hypoxic origin or as a consequence of an inflammatory processes.

As mentioned previously, atelectasis is associated with a dramatic reduction in blood flow to the nonventilated lung. Henry [18] demonstrated a metabolic depression in phospholipid synthesis during hypoperfusion of the lung that results in impaired surfactant activity. Other studies demonstrated that reperfusion of the ischemic lung results in alterations of pulmonary surfactant. Veldhuizen and coworkers [19] showed decreased concentrations of phosphatidylglycerol and surfactant protein A after lung transplantation, which was associated with significant hypoxemia during reperfusion. Furthermore, the in vitro function of surfactant from transplanted grafts decreased in parallel with prolongation of ischemic time [20].

There is some evidence that atelectasis and reperfusion initiate a cascade of events with neutrophil–endothelial cell adherence, activation, and production of toxic oxygen metabolites with subsequent capillary leak [21]. Surfactant function is severely compromised by the leakage of circulatory proteins into the alveolar air space. Many of these proteins, in particular fibrinogen and its products, react with surfactant and destroy its surface tension–lowering properties [22]. On the other hand, Qyarzun and colleagues [17] demonstrated a decreased quantity of alveolar surfactant and altered phospholipid composition in atelectatic lungs without evidence of inflammation and alveolar damage.

The question remains whether the newborn is more susceptible or less susceptible to these alterations of surfactant compared with the adult. There is some evidence that the answer is probably less susceptible. Surfactant quantity and composition change with lung maturation. Immediately after birth, surfactant pool size increases drastically in response to a number of stimuli. Ueda and coworkers [23] found that the alveolar-wash saturated phosphatidylcholine pool size was fivefold higher in newborn lambs than in adults. Furthermore, physiologic conversion of the heavy subtype of surfactant to the light subtype, ie, conversion of the newly secreted and active component of surfactant to the inactive form, seems to be less rapid in the newborn than in the adult animal [23].

The exact reason for impaired compliance after atelectasis because of OLV still remains unclear, and further investigations are necessary. In any case, immediate lung injury seems to be minimal in the newborn piglet. This fact is very promising and gives hope that even our youngest patients may profit from the new minimally invasive techniques in thoracic surgical procedures in the near future.

	References

Top Abstract Introduction Material and methods Results Comment References

 

1. Förster R., Mavroudis C. Thoracoscopic clipping of patent ductus arteriosus in premature infants. Ann Thorac Surg 1993;56:1418-1420.[Abstract]
2. Benumof J.L. Physiology of the lateral decubitus position, the open chest, and one-lung ventilation. In: Benumof J.L., ed. Anesthesia for thoracic surgery. New York: Saunders, 1987:193-221.
3. McGahren E.D., Kern J.A., Rodgers B.M. Anesthetic techniques for pediatric thoracoscopy. Ann Thorac Surg 1995;60:927-930.[Abstract/Free Full Text]
4. Tönz M., Bachmann D., Mettler D., Kaiser G. Effects of one-lung ventilation on pulmonary hemodynamics and gas exchange in the newborn. Eur J Pediatr Surg 1997;7:212-215.[Medline]
5. Tooley P., Hirschl R.B., Parent A., Bartlett R.H. Total liquid ventilation with perfluorocarbons increases pulmonary end-expiratory volume and compliance in the setting of lung atelectasis. Crit Care Med 1996;24:268-273.[Medline]
6. Goldmann G., Welbourn R., Rothlein R., et al. Adherent neutrophils mediate permeability after atelectasis. Ann Surg 1992;216:372-378.[Medline]
7. Lesouef P.N., England S.J., Bryan A.C. Passive respiratory mechanics in newborns and children. Am Rev Respir Dis 1984;129:552-556.[Medline]
8. Helfaer M.A., Nichols D.G., Rogers M.C. Developmental physiology of the respiratory system. In: Rogers M.C., ed. Textbook of pediatric intensive care, 2nd ed. Baltimore: Williams & Wilkins, 1992:104-133.
9. Staub N.C. Alveolar–arterial oxygen tension gradient due to diffusion. J Appl Physiol 1963;18:673-680.[Abstract/Free Full Text]
10. Hill E.P., Power G.G., Longo L.D. Kinetics of O₂ and CO₂ exchange. In: West J.B., ed. Bioengineering aspects of the lung. New York: Dekker, 1977:459-514.
11. Escourrou P., Qi X., Weiss M., et al. Influence of pulmonary blood flow on gas exchange in piglets. J Appl Physiol 1993;75:2478-2483.[Abstract/Free Full Text]
12. Sewell R.W., Fewel J.G., Grover F.L., Arom K.V. Experimental evaluation of reexpansion pulmonary edema. Ann Thorac Surg 1978;26:126-132.[Abstract]
13. Suzuki S., Tanita T., Koike K., Fujimura S. Evidence of acute inflammatory response in reexpansion pulmonary edema. Chest 1992;101:275-276.[Abstract/Free Full Text]
14. Tönz M., Mihaljevic T., von Segesser L.K., et al. Acute lung injury during cardiopulmonary bypass: are the neutrophils responsible?. Chest 1995;108:1551-1556.[Abstract/Free Full Text]
15. Zollinger A., Singer T., Kohler A., et al. Auswirkungen der Ein-Lungenventilation auf das extra-vaskuläre Lungenwasser und die Haemodynamik beim Schwein. Schweiz Med Wochenschr 1996;126(Suppl 83):8S.
16. Sutnick A.I., Soloff L.A. Surface tension reducing activity and atelectatic human lung. Am J Med 1963;35:31-36.[Medline]
17. Qyarzun M.J., Stevens P., Clements J.A. Effect of lung collapse on alveolar surfactant in rabbits subjected to unilateral pneumothorax. Exp Lung Res 1989;15:909-924.[Medline]
18. Henry J.N. The effect of shock on pulmonary alveolar surfactant. J Trauma 1968;8:756-773.[Medline]
19. Veldhuizen R.A.W., Lee J., Sandler D., Novick R.J. Alterations in pulmonary surfactant composition and activity after experimental lung transplantation. Am Rev Respir Dis 1993;148:208-215.[Medline]
20. Novick R.J., Gehmann K.E., Ali I.S., Lee J. Lung preservation: the importance of endothelial and alveolar type II cell integrity. Ann Thorac Surg 1996;62:302-314.[Abstract/Free Full Text]
21. Sugiura M., McCulloch P.R., Wren S., et al. Ventilator pattern influences neutrophil influx and activation in atelectasis-prone rabbit lung. J Appl Physiol 1994;77:1355-1365.[Abstract/Free Full Text]
22. Gross N.G. Pulmonary surfactant: unanswered questions. Thorax 1995;50:325-327.[Free Full Text]
23. Ueda T., Ikegami M., Jobe A.H. Developmental changes of sheep surfactant: in vivo function and in vitro subtype conversion. J Appl Physiol 1994;76:2701-2706.[Abstract/Free Full Text]

This article has been cited by other articles:

				E. R. Mariano, L. F. Chu, C. T. Albanese, and C. Ramamoorthy Successful Thoracoscopic Repair of Esophageal Atresia with Tracheoesophageal Fistula in a Newborn with Single Ventricle Physiology Anesth. Analg., October 1, 2005; 101(4): 1000 - 1002. [Abstract] [Full Text] [PDF]

				A. D. L. Sihoe, K. M. Ho, T. S. Sze, T. W. Lee, and A. P. C. Yim Selective lobar collapse for video-assisted thoracic surgery Ann. Thorac. Surg., January 1, 2004; 77(1): 278 - 283. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tönz, M. Articles by Kaiser, G. Search for Related Content PubMed PubMed Citation Articles by Tönz, M. Articles by Kaiser, G.