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GENERAL ARTICLES

Nitrous Oxide Fraction in the Carbon Dioxide Pneumoperitoneum During Laparoscopy Under General Inhaled Anesthesia in Pigs

Pierre A. Diemunsch, MD^*, Klaus D. Torp, MD, Thomas Van Dorsselaer^*, Didier Mutter, , MD, PhD^*, Anne M. Diemunsch, PhD^*, Roland Schaeffer, MD^*, Gérard Teller, PhD, and Alain Van Dorsselaer, PhD

*I.R.C.A.D., Hôpitaux Universitaires, Strasbourg, France; Mayo Clinic Jacksonville, Jacksonville, Florida; and L.S.M.B.O., Faculté de Chimie, Strasbourg, France

Address correspondence and reprint requests to P. A. Diemunsch, MD, I.R.C.A.D., Hôpitaux Universitaires, 1, Place de l’Hôpital, 67000 Strasbourg, France.

	Abstract

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During prolonged laparoscopy, the diffusion of other gases in the carbon dioxide (CO₂) pneumoperitoneum may lessen its safety. Nitrous oxide (N₂O)/CO₂ gas mixtures may become hazardous with regard to gas embolization and fire risk. We therefore evaluated the kinetics of pneumoperitoneal intrusion of N₂O. In five anesthetized domestic pigs, controlled ventilation, with an initial fraction of inspired oxygen = 1.0, was adjusted to keep ETCO₂ pressure between 35 and 45 mm Hg. The peritoneum was insufflated with CO₂ to a pressure of 12 mm Hg, which was maintained throughout the procedure. T0 was defined as the time when N₂O was introduced in the breathing circuit (N₂O end-tidal fraction = 66%). Gas samples (10 mL) from the pneumoperitoneum were analyzed every 10 min after T0. The N₂O concentration was measured by using capillary gas chromatography coupled with mass spectrometry. Percentages of N₂O in the CO₂ increased with time (t) according to the ideal equation: N₂O_(t) = 66 (1 - exp^-0.005t). In the peritoneal cavity, <2 h were required for the N₂O to reach the concentration of 29%, which can support combustion. Eight hours to 10 h after T0, the intraperitoneal N₂O fraction approaches the level of the N₂O end-tidal fraction. Options to prevent accumulation of N₂O are suggested.

Implications: Pig models were used to evaluate the time course of nitrous oxide (N₂O) diffusion in the pneumoperitoneum during nitrous oxide/oxygen anesthesia. Although peritoneal N₂O concentration approaches the end-expiratory value after 8–10 h, it reaches 29% within 2 h. At this level, N₂O is known to support combustion. This N₂O pollution should be prevented.

	Introduction

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Carbon dioxide (CO₂) is a commonly used gas for pneumoperitoneum insufflation during laparoscopic surgery for 3 main reasons: 1) lack of toxicity, 2) high solubility in blood, and 3) no support of combustion. Systemic absorption and subsequent elimination of CO₂ by the lungs have been well studied. Conversely, only a few studies have dealt with the diffusion of other gases from the body into the CO₂ pneumoperitoneum (1,2). The aim of this study was to quantitatively evaluate the contamination of the CO₂ pneumoperitoneum by inhaled nitrous oxide (N₂O) during long-lasting general anesthesia, to assess the magnitude and the time course of the potential impairment of its safety.

	Methods

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After institutional approval was obtained, 5 domestic pigs with a mean weight of 29 ± 1.4 kg underwent laparoscopy during general anesthesia. The induction of anesthesia was achieved with IM administration of ketamine (20 mg/kg) and azaperone (2 mg/kg). An IV line (22-gauge) was inserted into an auricular vein, and endotracheal intubation was facilitated by pancuronium (0.1 mg/kg). Anesthesia and neuromuscular blockade were maintained with isoflurane up to a maximum of 1.5 vol% end-tidal fraction (Fet) and pancuronium (0.1 mg kg^-1 · h^-1) IV, respectively. Ventilation was maintained using a Dräger Cicero^® ventilator (Dräger Médical, Antony France) with an initial fraction of inspired oxygen of 100% and a fresh gas flow of 2.0 L/min. Minute ventilation (E) was adjusted to keep PETCO₂ between 35 and 45 mm Hg. A Veress needle was inserted on the midline at the lower part of the umbilicus, and a pneumoperitoneum was produced by insufflation with a Striker^® (Striker, San Jose, CA) insufflator, by using CO₂ to an intraperitoneal pressure of 12 mm Hg, which was maintained throughout the procedure by reinsufflation of CO₂. A pneumoperitoneum gas-sampling catheter was inserted percutaneously into the right flank, under endoscopic video guidance, to keep the catheter tip at a distance from the insufflation port.

At T0, N₂O was introduced in the breathing circuit with an inspired fraction (FI) N₂O of 66% in oxygen (the fresh gas flow was increased to 12 L/min to achieve the desired FI N₂O of 66% in seconds and then reduced to 2 L/min again). Every 10 min after T0, a 10-mL sample of gas was taken from the pneumoperitoneum through the gas-sampling catheter with a gas-tight syringe and analyzed for N₂O and CO₂. Continuous monitoring included: electrocardiogram, peritoneal pressure, total volume of CO₂ insufflated, SpO₂ by pulse oximetry, PETCO₂, FI N₂O, Fet N₂O, FI isoflurane, Fet isoflurane, fraction of inspired oxygen, E, and peak inspiratory pressure.

To measure the different gas concentrations, we used a gas chromatograph-mass spectrometer (MD 800 GC-MS, FISONS, Manchester, UK) with a mass range of 2 to 800, fitted with a capillary column (25 m x 0.32 mm) and coated with GS-Q stationary phase (J and W SCIENTIFIC, Folsom, CA). The split ratio was 1/100, and the velocity of the carrier gas (helium, 112.52 mm Hg) was 0.6 m/s. The column temperature was 28°C. Gas samples (5 µL) were taken from the 10-mL sample syringes through a septum with a gas-tight syringe and then directly injected into the gas chromatograph. Compounds were eluted in the following order: N₂ (1.25 min), O₂ (1.30 min), CO₂ (1.85 min), and N₂O (2.10 min).

The mass spectrometer was scanning from mass-to-charge ratio (m/z) = 4 to m/z = 50 in 0.1 s. Detection was performed by extraction of ion chromatograms from the spectra recorded. The molecular ion chromatogram of N₂O and CO₂ (m/z = 44) was used for relative quantification. The response factor of N₂O relative to CO₂ was determined by using a 1/1 (volume/volume) mixture of N₂O/CO₂, and the ratio was established as 0.8. Chromatographic peak areas were used for determining relative amounts. Other information was given by ion chromatogram 30 (specific fragmentation of N₂O), ion chromatogram 28 (molecular ion of N₂ and fragment of CO₂), and ion chromatogram 32 (O₂ molecular ion). All measurements were made in duplicate.

The experimental data were shown in a two-dimensional scatter diagram. The equation of the expected amount of N₂O in the pneumoperitoneum with time was determined by using a growth model:

where represents the value of N₂O when t tends to infinity (i.e., N₂O maximum = 66% in our setting). The rate of uptake constant k is obtained after linearizing the equation:

Linear regression analysis is then possible and estimates k as well as the 95% confidence interval of k, P value of the F statistics of regression, and the Pearson coefficient of correlation. The statistics were performed by using Statview software (Abacus Concepts, Berkeley, CA).

	Results

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The initial volume of CO₂ necessary to reach a pneumoperitoneal pressure of 12 mm Hg was 3.4 ± 0.8 L. Thereafter, the compensatory CO₂ insufflation flow needed to maintain this pressure was 3.5 ± 0.8 L/h. The other experimental conditions are summarized in Table 1. The duration of the experiments ranged from 120 to 530 min.

View larger version (16K): [in this window] [in a new window]   Figure 1. Evolution of the nitrous oxide (N2O) concentration in the carbon dioxide (CO2) pneumoperitoneum in 5 pigs. Eight to 10 h after starting inhalation of nitrous oxide, the intraperitoneal N2O fraction appeared to approach a possible plateau at the level of the end-tidal N2O value. The bold line represents the calculated ideal curve: N2O(t) = 66 (1 - exp-0.005t).

	Discussion

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In our model, pneumoperitoneal CO₂ turnover was minimal because of the absence of surgical leaks. Those conditions may be similar during long-lasting laparoscopic dissections or adhesiolysis. The duration of our experiments increased with each pig, because we were unable to anticipate the approximate time for an equilibrium to occur. Owing to the expected complexity of the gas mixture in the abdomen, as well as the wide range of concentrations to be measured, we used two consecutive separation methods: gas chromatography coupled with mass spectrometry.

As we demonstrated, with time the pneumoperitoneum consisted of less CO₂ and more N₂O. This gas mixture may be less safe than plain CO₂ with regard to fire, explosion, or gas embolization hazards.

The risk of fire or explosion during laparoscopy with a pneumoperitoneal gas other than pure CO₂ is based on several case reports (4–7). N₂O, O₂, and mixtures of both gases with CO₂ have resulted in severe injuries or death in these patients. Three conditions must be met to produce a flame: first, a fire-supporting atmosphere; second, an ignition source; and third, flammable material. According to data provided by Neuman et al. (2), a concentration of 29% N₂O in CO₂ may be sufficient to support combustion. In the case of a bowel perforation, release of the flammable material (intestinal H₂ and CH₄) may ensue, and a spark from a cautery device or a laser could add the ignition source, as suggested in case reports of colonic explosions (8,9). In our experimental conditions, N₂O concentration in the peritoneal cavity reaches 29% in <two hours.

Several case reports have been published regarding gas embolization during laparoscopy (10,11) during insufflation of a CO₂ pneumoperitoneum as well as after its release. N₂O potentiates the consequences of a CO₂ gas embolism (12) by diffusing into the gas bubble in exchange for CO₂. The size of the embolus is not likely to increase because of the similar solubility coefficient (0.47 and 0.49 Ostwald, respectively) (13,14). The resulting mixed gas embolus will be eliminated slower if the patient is breathing N₂O, owing to the lack of a diffusion gradient. Even by withdrawing N₂O from the breathing circuit, the N₂O-rich pneumoperitoneum may represent an internal reservoir of N₂O, feeding the gas embolus, hence, slowing its elimination by the respiratory system.

In summary, we have demonstrated the time course of the diffusion of inhaled N₂O into the CO₂ pneumoperitoneum. We also discussed potential deleterious effects of the contamination of a pure CO₂ pneumoperitoneum with N₂O based on physics and reports in the literature. The risks of the resulting complications are small, based on the few case reports, compared with the number of laparoscopies performed. Nevertheless, the consequences of the events are severe enough that appropriate measures are warranted to avoid them. One possibility would be to avoid N₂O during laparoscopic procedures. The second option would be to create a calibrated leak in the pneumoperitoneum, compensated for by fresh CO₂ to dilute other gases to a safe level.

	References

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1. Cameron AE, Dear GL, Pocock TJ, Tennant RW. Gas exchange in abdominal cavity during laparoscopy. J R Soc Med 1983;76:1015–8.[Abstract]
2. Neuman GG, Sidebotham G, Negoianu E, et al. Laparoscopy explosion hazards with nitrous oxide. Anesthesiology 1993;78:875–9.[Web of Science][Medline]
3. Draper NR, Smith H. Applied regression analysis. 3rd ed. New York:John Wiley & Sons, 1998:543–9.
4. El-Kady AA, Abd-El-Razek M. Intraperitoneal explosion during female sterilization by laparoscopic electrocoagulation: a case report. Int J Gynaecol Obstet 1976;14:487–8.[Medline]
5. Greilich PE, Greilich NB, Froelich EG. Intraabdominal fire during laparoscopic cholecystectomy. Anesthesiology 1995;83:871–4.[Web of Science][Medline]
6. Gunatilake DE. Case report: fatal intraperitoneal explosion during electrocoagulation via laparoscopy. Gynaecol Obstet 1978;15:353–7.
7. Use of wrong gas in laparoscopic insufflator causes fire. Health Devices 1994;23:55–6.[Medline]
8. Bigard MA, Gaucher P, Lassalle C. Fatal colonic explosion during colonoscopic polypectomy. Gastroenterology 1979;77:1307–10.[Web of Science][Medline]
9. Shinagawa N, Mizuno H, Shibata Y, et al. Gas explosion during diathermy colotomy. Br J Surg 1985;72:306.[Web of Science][Medline]
10. Beck DH, McQuillan PJ. Fatal carbon dioxide embolism and severe haemorrhage during laparoscopic salpingectomy. Br J Anaesth 1994;72:243–5.[Abstract/Free Full Text]
11. Root B, Levy MN, Pollack S, et al. Gas embolism death after laparoscopy delayed by "trapping" in portal circulation. Anesth Analg 1978;57:232–7.[Abstract/Free Full Text]
12. Steffey EP, Johnson BH, Eger EI II. Nitrous oxide intensifies the pulmonary arterial pressure response to venous injection of carbon dioxide in the dog. Anesthesiology 1980;52:52–5.[Web of Science][Medline]
13. Hill DW. Physics applied to anesthesia. 4th ed. London:Butterworths, 1980:212.
14. Parbrook GD, Davis PD, Parbrook EO. Basic physics and measurement in anaesthesia. 3rd ed. Oxford:Butterworth-Heinemann, 1990:83.

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Diemunsch, P. A. Articles by Van Dorsselaer, A. Search for Related Content PubMed PubMed Citation Articles by Diemunsch, P. A. Articles by Van Dorsselaer, A.