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Hypercapnia and acidosis during the thoracoscopic repair of oesophageal atresia and congenital diaphragmatic hernia
Journal of Pediatric Surgery 50 (2015) 247–249
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Hypercapnia and acidosis during the thoracoscopic repair of oesophageal atresia and congenital diaphragmatic hernia Agostino Pierro ⁎ Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
a r t i c l e
i n f o
Article history: Received 21 October 2014 Accepted 2 November 2014 Key words: Oesophageal atresia Congenital diaphragmatic hernia Thoracoscopy Minimally invasive surgery Acidosis Hypercapnia
a b s t r a c t Thoracoscopic operations in neonates, such as repair of oesophageal atresia and tracheooesophageal fistula or congenital diaphragmatic hernia, can be associated with intraoperative acidosis and hypercapnia in the absence of hypoxia. These derangements in intraoperative gas exchanges seem to be related to the insufflation and absorption of medical CO2. The effects on the developing brain are unknown, and further prospective investigations are needed to elucidate whether different strategies should be implemented to avoid these intraoperative problems. © 2015 Published by Elsevier Inc.
Application of minimally invasive surgery (MIS) in paediatrics became a logical next step following its success in adults. However, the use of such minimally invasive techniques in young children spread relatively slowly because: the surgical instruments had to be downsized; the learning curve was relatively long; and safe and hence reliable techniques of anaesthesia had to be developed. More recently, with the acceleration in technology, the number of these procedures in children has been rising rapidly and in leading institutions MIS is now performed in approximately 70% of children. Thoracoscopic repair of oesophageal atresia with or without tracheoesophageal fistula (OA/TOF) or congenital diaphragmatic hernia (CDH) in neonates and infants has been one of the most recent and challenging applications of MIS in neonates. Despite these rapid advances, there is a paucity of information on the intraoperative physiology during MIS during the neonatal period. Of particular importance, recent evidence indicates that profound intraoperative acidosis and hypercapnia can occur during advanced thoracoscopic surgery [1]. This report focuses on gas exchanges during thoracoscopy for the correction of OA/TOF or CDH and on the implications for further investigations and treatment. 1. Hypercapnia and acidosis Thoracoscopic repair requires CO2 insufflation to create the working space. CO2 is the gas of choice as it is non-combustible, inexpensive and ⁎ Division Head, Pediatric Surgery, Robert M. Filler Professor of Surgery, Program Director, University of Toronto, The Hospital for Sick Children, 1526-555 University Ave, Toronto, ON M5G 1X8, Canada. Tel.: +1 416 813 7340; fax: +1 416 813 7477. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.jpedsurg.2014.11.006 0022-3468/© 2015 Published by Elsevier Inc.
unlikely to cause embolism. However, the effect of CO2 on intraoperative gas exchange may be a cause of some concern. The author and his collaborators during their early experience of thoracoscopic procedures at Great Ormond Street Hospital noticed a degree of intraoperative hypercapnia and acidosis in neonates [2]. This was possibly because of CO2 insufflation into the pleural cavity and collapse/reduced ventilation of the ipsilateral lung in an immature and often pathological neonatal cardiopulmonary system. At the time of this initial observation there were few studies reporting on the cardiorespiratory consequences of thoracoscopy in neonates [3–5], and these relied upon a retrospective review of anaesthetic charts. Other authors had noticed the same phenomenon and one recent retrospective case series [6] reported high frequency oscillatory ventilation (HFOV) as an alternative ventilatory strategy to reduce hypercapnia. However, this strategy may increase the difficulty and duration of the operation as well as the risk of technical complications. Our preliminary observation [2] became of great concern to surgeons, anaesthesists and neonatologists and we decided to elucidate our initial retrospective observation and perform a prospective pilot randomized controlled trial using a well-defined protocol [1]. Eligible patients were neonates (i.e. in the first month of life) with OA/TOF or CDH and not requiring HFOV, inhaled nitric oxide, or inotropic support for at least 24 hours. Those weighing b 1.6 kg or requiring N40% oxygen were excluded, as were neonates who had required extracorporeal membrane oxygenation (ECMO) or had major congenital heart defects, pulmonary hypertension, or bilateral grade IV intraventricular hemorrhage. Participants were randomly allocated to open or thoracoscopic surgery in a 1:1 ratio using computerized balanced minimization with the following criteria: (i) diagnosis (CHD or OA/TOF), (ii) weight at the time of enrolment in the study (b 2.5 or N2.5 kg), and (iii) age at
248
A. Pierro / Journal of Pediatric Surgery 50 (2015) 247–249
the time of enrollment (b7 or ≥7 days). Thoracoscopy was performed with both lungs ventilated and the chest was insufflated using CO2 and, if possible, the initial pressure was reduced after reduction of hernia contents (CDH) or after collapse of the lung (OA/TOF). The insufflation pressure was increased for a transient period if thought necessary to maintain visualization. The trial protocol specified that if ventilation was felt to be a significant concern during thoracoscopy, insufflation of CO2 would be temporarily paused to allow improvement in ventilation. If this was not successful, the operation would be converted to open surgery. Overall, the intraoperative PaCO2 was 61 mm Hg in open and 83 mm Hg [difference 22 mm Hg (2 to 42); P = 0.036] in thoracoscopy and the pH was 7.24 in open and 7.13 [difference − 0.11 (− 0.20 to − 0.01); P = 0.025] in thoracoscopy. The duration of hypercapnia and acidosis was longer in thoracoscopy compared with that in open. For patients with CDH, thoracoscopy was associated with a significant increase in intraoperative hypercapnia [open 68 mm Hg; thoracoscopy 96 mm Hg; difference 28 mm Hg (8 to 48); P = 0.008] and severe acidosis [open 7.21; thoracoscopy 7.08; difference − 0.13 (− 0.24 to −0.02); P = 0.018] (Fig. 1). The changes observed in PaCO2 and pH in the neonates undergoing thoracoscopic repair of EA/TEF were not significant. None of the children during this trial suffered from hypoxia and the multilevel regression modeling used to compare intraoperative blood gases indicated that thoracoscopy was associated with a significant increase in intraoperative hypercapnia and acidosis, whereas oxygenation was not different. There were no cases of thoracoscopy converted to open surgery because of ventilatory concerns; in one case the anesthesiologist requested a 6 minutes pause of insufflation during thoracoscopy because of concerns regarding hypercapnia which improved after hand ventilation and aspiration of secretions. The degree of hypercapnia and acidosis observed during this pilot randomized controlled trial were concerning and the Data Monitoring Ethic Committee advised that thoracoscopic repair of CDH should no longer be performed with this type of conventional insufflation and ventilation. The Trial Steering Committee of the trial accepted these recommendations and the thoracoscopic repair of CDH was no longer performed with the methods described above at the Institution randomizing the patients.
There are alternatives to reduce hypercapnia using alternative insufflation gases such as helium, argon, nitrogen, or even air for insufflations; but none of these dissolve as rapidly as CO2, resulting in a potential risk of embolism and none are as cheap as CO2. There are no clinical studies using an alternative gas source for insufflation during the thoracoscopic repair of OA/TEF or CDH. The insufflation pressure has been thought to be associated with intraoperative hypercapnia and acidosis. However, during thoracoscopy in the pilot trial [1], initial insufflation pressure was 7.1 ± 0.5 mm Hg; this was reduced or maintained in all patients except one neonate undergoing repair of CDH, where an increase from 6 to 9 mm Hg was necessary to achieve visualization. A possible strategy to minimize hypercapnia and acidosis would be to use CO2 insufflation only at the beginning of the operation, to help the reduction of the herniated abdominal contents into the peritoneal cavity. Once this been achieved, insufflation pressure could be decreased or potentially discontinued. All these alternative ventilation/insufflation strategies could be investigated in further prospective studies. The rate of absorption of CO2 insufflated during minimally invasive surgery is of interest. Recently, Eaton et al. [7–9] described a novel technique for the measurement of CO2 absorbed during MIS which enables absorbed CO2 from insufflation to be distinguished from metabolic CO2. Bishay et al [1] in the pilot trial reported that up to 39 ± 3% (range, 32–59%) of exhaled CO2 was derived from insufflated gas, rather than being of metabolic origin and that there was no significant difference in absorption of insufflated CO2 between OA/TOF and CDH patients in the absorption of CO2 (Fig. 2). Similarly other authors have indicated that CO2 absorption is highest in infants and during thoracoscopy [10]. However, the rate of absorption of CO2 during laparoscopy (approximately 20%) seems to be smaller than during thoracoscopy. Further characterization of this phenomenon is urgently needed. There have been no reports indicating a potential harm of thoracoscopy, acidosis and hypercapnia on the developing brain leading to neurodevelopmental delay. In particular it is not known whether acidosis and hypercapnia in the presence of normoxia are detrimental. Although hypercapnia and acidosis are associated with adverse outcome in neonates with hypoxia as observed in hypoxic
Fig. 1. Intraoperative blood gases: peak intraoperative PaCO2 and nadir intraoperative pH. Data compared using unpaired t test (reprinted with permission from Ann Surg 2013) [1].
A. Pierro / Journal of Pediatric Surgery 50 (2015) 247–249
249
support anaesthetic management, surgical technique and training not only for infants with OA/TEF or CDH but also for neonates with other neonatal conditions that may benefit from thoracoscopic surgery. Acknowledgement This publication was supported by the endowment of the Robert M. Filler Chair. References
Fig. 2. Percentage of CO2 absorption from insufflation during minimally invasive surgery: the absorption after EA/TEF or CDH repair is not different (reprinted with permission from Ann Surg 2013) [1].
encephalopathy, the neonates undergoing thoracoscopy did not show changes in arterial oxygenation, so the effects of these physiological changes on future brain development remain unknown. In the UK, the National Institute of Health and Clinical Excellence (NICE) guidelines on the use of thoracoscopy for the repair of CDH in neonates support the use of this procedure [11], but do not address safety concerns related to hypercapnia and acidosis. However, in this report, NICE “encourages collection of data and publication of results” on this procedure.
2. Conclusions Recent studies have indicated that the thoracoscopic repair of OA/TOF or CDH can be associated with hypercapnia and acidosis. At present there is lack of good evidence indicating negative effects of thoracoscopy, hypercapnia and acidosis in the presence of normoxia on the brain and on the child’s neurological development. Further studies are needed to elucidate these effects and to determine whether thoracoscopy is safe and not impairing future quality of life. This information would
[1] Bishay M, Giacomello L, Retrosi G, et al. Hypercapnia and acidosis during open and thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia: results of a pilot randomized controlled trial. Ann Surg 2013;258:895–900. [2] McHoney M, Giacomello L, Nah SA, et al. Thoracoscopic repair of congenital diaphragmatic hernia: intraoperative ventilation and recurrence. J Pediatr Surg 2010;45:355–9. [3] Bliss D, Matar M, Krishnaswami S. Should intraoperative hypercapnea or hypercarbia raise concern in neonates undergoing thoracoscopic repair of diaphragmatic hernia of Bochdalek? J Laparoendosc Adv Surg Tech A 2009;19(Suppl. 1): S55–8. [4] Gourlay DM, Cassidy LD, Sato TT, et al. Beyond feasibility: a comparison of newborns undergoing thoracoscopic and open repair of congenital diaphragmatic hernias. J Pediatr Surg 2009;44:1702–7. [5] Krosnar S, Baxter A. Thoracoscopic repair of esophageal atresia with tracheoesophageal fistula: anesthetic and intensive care management of a series of eight neonates. Paediatr Anaesth 2005;15:541–6. [6] Mortellaro VE, Fike FB, Adibe OO, et al. The use of high-frequency oscillating ventilation to facilitate stability during neonatal thoracoscopic operations. J Laparoendosc Adv Surg Tech A 2011;21:877–9. [7] Eaton S, McHoney M, Giacomello L, et al. Carbon dioxide absorption and elimination in breath during minimally invasive surgery. J Breath Res 2009;3:047005. http://dx. doi.org/10.1088/1752-7155/3/4/047005 [Epub 2009 Nov 27]. [8] Eaton S, Pacilli M, Wood J, et al. Factors affecting 13C-natural abundance measurement of breath carbon dioxide during surgery: absorption of carbon dioxide during endoscopic procedures. Rapid Commun Mass Spectrom 2008;22:1759–62. [9] Pacilli M, Pierro A, Kingsley C, et al. Absorption of carbon dioxide during laparoscopy in children measured using a novel mass spectrometric technique. Br J Anaesth 2006;97:215–9. [10] Tobias JD. Anaesthetic implications of thoracoscopic surgery in children. Paediatr Anaesth 1999;9:103–10. [11] National Institute of Health and Clinical Excellence (NICE). IPG379 thoracoscopic repair of congenital diaphragmatic hernia in neonates. Available at http://guidance. nice.org.uk/IPG379/Guidance/pdf/English; 2011. [September 10, 2012].
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Hypercapnia and acidosis during the thoracoscopic repair of oesophageal atresia and congenital diaphragmatic hernia Agostino Pierro ⁎ Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
a r t i c l e
i n f o
Article history: Received 21 October 2014 Accepted 2 November 2014 Key words: Oesophageal atresia Congenital diaphragmatic hernia Thoracoscopy Minimally invasive surgery Acidosis Hypercapnia
a b s t r a c t Thoracoscopic operations in neonates, such as repair of oesophageal atresia and tracheooesophageal fistula or congenital diaphragmatic hernia, can be associated with intraoperative acidosis and hypercapnia in the absence of hypoxia. These derangements in intraoperative gas exchanges seem to be related to the insufflation and absorption of medical CO2. The effects on the developing brain are unknown, and further prospective investigations are needed to elucidate whether different strategies should be implemented to avoid these intraoperative problems. © 2015 Published by Elsevier Inc.
Application of minimally invasive surgery (MIS) in paediatrics became a logical next step following its success in adults. However, the use of such minimally invasive techniques in young children spread relatively slowly because: the surgical instruments had to be downsized; the learning curve was relatively long; and safe and hence reliable techniques of anaesthesia had to be developed. More recently, with the acceleration in technology, the number of these procedures in children has been rising rapidly and in leading institutions MIS is now performed in approximately 70% of children. Thoracoscopic repair of oesophageal atresia with or without tracheoesophageal fistula (OA/TOF) or congenital diaphragmatic hernia (CDH) in neonates and infants has been one of the most recent and challenging applications of MIS in neonates. Despite these rapid advances, there is a paucity of information on the intraoperative physiology during MIS during the neonatal period. Of particular importance, recent evidence indicates that profound intraoperative acidosis and hypercapnia can occur during advanced thoracoscopic surgery [1]. This report focuses on gas exchanges during thoracoscopy for the correction of OA/TOF or CDH and on the implications for further investigations and treatment. 1. Hypercapnia and acidosis Thoracoscopic repair requires CO2 insufflation to create the working space. CO2 is the gas of choice as it is non-combustible, inexpensive and ⁎ Division Head, Pediatric Surgery, Robert M. Filler Professor of Surgery, Program Director, University of Toronto, The Hospital for Sick Children, 1526-555 University Ave, Toronto, ON M5G 1X8, Canada. Tel.: +1 416 813 7340; fax: +1 416 813 7477. E-mail address: [email protected]. http://dx.doi.org/10.1016/j.jpedsurg.2014.11.006 0022-3468/© 2015 Published by Elsevier Inc.
unlikely to cause embolism. However, the effect of CO2 on intraoperative gas exchange may be a cause of some concern. The author and his collaborators during their early experience of thoracoscopic procedures at Great Ormond Street Hospital noticed a degree of intraoperative hypercapnia and acidosis in neonates [2]. This was possibly because of CO2 insufflation into the pleural cavity and collapse/reduced ventilation of the ipsilateral lung in an immature and often pathological neonatal cardiopulmonary system. At the time of this initial observation there were few studies reporting on the cardiorespiratory consequences of thoracoscopy in neonates [3–5], and these relied upon a retrospective review of anaesthetic charts. Other authors had noticed the same phenomenon and one recent retrospective case series [6] reported high frequency oscillatory ventilation (HFOV) as an alternative ventilatory strategy to reduce hypercapnia. However, this strategy may increase the difficulty and duration of the operation as well as the risk of technical complications. Our preliminary observation [2] became of great concern to surgeons, anaesthesists and neonatologists and we decided to elucidate our initial retrospective observation and perform a prospective pilot randomized controlled trial using a well-defined protocol [1]. Eligible patients were neonates (i.e. in the first month of life) with OA/TOF or CDH and not requiring HFOV, inhaled nitric oxide, or inotropic support for at least 24 hours. Those weighing b 1.6 kg or requiring N40% oxygen were excluded, as were neonates who had required extracorporeal membrane oxygenation (ECMO) or had major congenital heart defects, pulmonary hypertension, or bilateral grade IV intraventricular hemorrhage. Participants were randomly allocated to open or thoracoscopic surgery in a 1:1 ratio using computerized balanced minimization with the following criteria: (i) diagnosis (CHD or OA/TOF), (ii) weight at the time of enrolment in the study (b 2.5 or N2.5 kg), and (iii) age at
248
A. Pierro / Journal of Pediatric Surgery 50 (2015) 247–249
the time of enrollment (b7 or ≥7 days). Thoracoscopy was performed with both lungs ventilated and the chest was insufflated using CO2 and, if possible, the initial pressure was reduced after reduction of hernia contents (CDH) or after collapse of the lung (OA/TOF). The insufflation pressure was increased for a transient period if thought necessary to maintain visualization. The trial protocol specified that if ventilation was felt to be a significant concern during thoracoscopy, insufflation of CO2 would be temporarily paused to allow improvement in ventilation. If this was not successful, the operation would be converted to open surgery. Overall, the intraoperative PaCO2 was 61 mm Hg in open and 83 mm Hg [difference 22 mm Hg (2 to 42); P = 0.036] in thoracoscopy and the pH was 7.24 in open and 7.13 [difference − 0.11 (− 0.20 to − 0.01); P = 0.025] in thoracoscopy. The duration of hypercapnia and acidosis was longer in thoracoscopy compared with that in open. For patients with CDH, thoracoscopy was associated with a significant increase in intraoperative hypercapnia [open 68 mm Hg; thoracoscopy 96 mm Hg; difference 28 mm Hg (8 to 48); P = 0.008] and severe acidosis [open 7.21; thoracoscopy 7.08; difference − 0.13 (− 0.24 to −0.02); P = 0.018] (Fig. 1). The changes observed in PaCO2 and pH in the neonates undergoing thoracoscopic repair of EA/TEF were not significant. None of the children during this trial suffered from hypoxia and the multilevel regression modeling used to compare intraoperative blood gases indicated that thoracoscopy was associated with a significant increase in intraoperative hypercapnia and acidosis, whereas oxygenation was not different. There were no cases of thoracoscopy converted to open surgery because of ventilatory concerns; in one case the anesthesiologist requested a 6 minutes pause of insufflation during thoracoscopy because of concerns regarding hypercapnia which improved after hand ventilation and aspiration of secretions. The degree of hypercapnia and acidosis observed during this pilot randomized controlled trial were concerning and the Data Monitoring Ethic Committee advised that thoracoscopic repair of CDH should no longer be performed with this type of conventional insufflation and ventilation. The Trial Steering Committee of the trial accepted these recommendations and the thoracoscopic repair of CDH was no longer performed with the methods described above at the Institution randomizing the patients.
There are alternatives to reduce hypercapnia using alternative insufflation gases such as helium, argon, nitrogen, or even air for insufflations; but none of these dissolve as rapidly as CO2, resulting in a potential risk of embolism and none are as cheap as CO2. There are no clinical studies using an alternative gas source for insufflation during the thoracoscopic repair of OA/TEF or CDH. The insufflation pressure has been thought to be associated with intraoperative hypercapnia and acidosis. However, during thoracoscopy in the pilot trial [1], initial insufflation pressure was 7.1 ± 0.5 mm Hg; this was reduced or maintained in all patients except one neonate undergoing repair of CDH, where an increase from 6 to 9 mm Hg was necessary to achieve visualization. A possible strategy to minimize hypercapnia and acidosis would be to use CO2 insufflation only at the beginning of the operation, to help the reduction of the herniated abdominal contents into the peritoneal cavity. Once this been achieved, insufflation pressure could be decreased or potentially discontinued. All these alternative ventilation/insufflation strategies could be investigated in further prospective studies. The rate of absorption of CO2 insufflated during minimally invasive surgery is of interest. Recently, Eaton et al. [7–9] described a novel technique for the measurement of CO2 absorbed during MIS which enables absorbed CO2 from insufflation to be distinguished from metabolic CO2. Bishay et al [1] in the pilot trial reported that up to 39 ± 3% (range, 32–59%) of exhaled CO2 was derived from insufflated gas, rather than being of metabolic origin and that there was no significant difference in absorption of insufflated CO2 between OA/TOF and CDH patients in the absorption of CO2 (Fig. 2). Similarly other authors have indicated that CO2 absorption is highest in infants and during thoracoscopy [10]. However, the rate of absorption of CO2 during laparoscopy (approximately 20%) seems to be smaller than during thoracoscopy. Further characterization of this phenomenon is urgently needed. There have been no reports indicating a potential harm of thoracoscopy, acidosis and hypercapnia on the developing brain leading to neurodevelopmental delay. In particular it is not known whether acidosis and hypercapnia in the presence of normoxia are detrimental. Although hypercapnia and acidosis are associated with adverse outcome in neonates with hypoxia as observed in hypoxic
Fig. 1. Intraoperative blood gases: peak intraoperative PaCO2 and nadir intraoperative pH. Data compared using unpaired t test (reprinted with permission from Ann Surg 2013) [1].
A. Pierro / Journal of Pediatric Surgery 50 (2015) 247–249
249
support anaesthetic management, surgical technique and training not only for infants with OA/TEF or CDH but also for neonates with other neonatal conditions that may benefit from thoracoscopic surgery. Acknowledgement This publication was supported by the endowment of the Robert M. Filler Chair. References
Fig. 2. Percentage of CO2 absorption from insufflation during minimally invasive surgery: the absorption after EA/TEF or CDH repair is not different (reprinted with permission from Ann Surg 2013) [1].
encephalopathy, the neonates undergoing thoracoscopy did not show changes in arterial oxygenation, so the effects of these physiological changes on future brain development remain unknown. In the UK, the National Institute of Health and Clinical Excellence (NICE) guidelines on the use of thoracoscopy for the repair of CDH in neonates support the use of this procedure [11], but do not address safety concerns related to hypercapnia and acidosis. However, in this report, NICE “encourages collection of data and publication of results” on this procedure.
2. Conclusions Recent studies have indicated that the thoracoscopic repair of OA/TOF or CDH can be associated with hypercapnia and acidosis. At present there is lack of good evidence indicating negative effects of thoracoscopy, hypercapnia and acidosis in the presence of normoxia on the brain and on the child’s neurological development. Further studies are needed to elucidate these effects and to determine whether thoracoscopy is safe and not impairing future quality of life. This information would
[1] Bishay M, Giacomello L, Retrosi G, et al. Hypercapnia and acidosis during open and thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia: results of a pilot randomized controlled trial. Ann Surg 2013;258:895–900. [2] McHoney M, Giacomello L, Nah SA, et al. Thoracoscopic repair of congenital diaphragmatic hernia: intraoperative ventilation and recurrence. J Pediatr Surg 2010;45:355–9. [3] Bliss D, Matar M, Krishnaswami S. Should intraoperative hypercapnea or hypercarbia raise concern in neonates undergoing thoracoscopic repair of diaphragmatic hernia of Bochdalek? J Laparoendosc Adv Surg Tech A 2009;19(Suppl. 1): S55–8. [4] Gourlay DM, Cassidy LD, Sato TT, et al. Beyond feasibility: a comparison of newborns undergoing thoracoscopic and open repair of congenital diaphragmatic hernias. J Pediatr Surg 2009;44:1702–7. [5] Krosnar S, Baxter A. Thoracoscopic repair of esophageal atresia with tracheoesophageal fistula: anesthetic and intensive care management of a series of eight neonates. Paediatr Anaesth 2005;15:541–6. [6] Mortellaro VE, Fike FB, Adibe OO, et al. The use of high-frequency oscillating ventilation to facilitate stability during neonatal thoracoscopic operations. J Laparoendosc Adv Surg Tech A 2011;21:877–9. [7] Eaton S, McHoney M, Giacomello L, et al. Carbon dioxide absorption and elimination in breath during minimally invasive surgery. J Breath Res 2009;3:047005. http://dx. doi.org/10.1088/1752-7155/3/4/047005 [Epub 2009 Nov 27]. [8] Eaton S, Pacilli M, Wood J, et al. Factors affecting 13C-natural abundance measurement of breath carbon dioxide during surgery: absorption of carbon dioxide during endoscopic procedures. Rapid Commun Mass Spectrom 2008;22:1759–62. [9] Pacilli M, Pierro A, Kingsley C, et al. Absorption of carbon dioxide during laparoscopy in children measured using a novel mass spectrometric technique. Br J Anaesth 2006;97:215–9. [10] Tobias JD. Anaesthetic implications of thoracoscopic surgery in children. Paediatr Anaesth 1999;9:103–10. [11] National Institute of Health and Clinical Excellence (NICE). IPG379 thoracoscopic repair of congenital diaphragmatic hernia in neonates. Available at http://guidance. nice.org.uk/IPG379/Guidance/pdf/English; 2011. [September 10, 2012].