Free
Pain Medicine  |   February 2002
Diffusion of Xenon and Nitrous Oxide into the Bowel during Mechanical Ileus
Author Affiliations & Notes
  • Helmut Reinelt, M.D.
    *
  • Thomas Marx, M.D.
  • Uwe Schirmer, M.D.
  • Sibylle Luederwald
    §
  • Pantelis Topalidis
    §
  • Michael Schmidt, M.D.
    *
  • *Staff Anesthesiologist, † Staff Anesthesiologist and Leader of the Xenon Research Group, ‡ Head of the Department, § Student, Department of Cardiac Anesthesia, University of Ulm.
  • Received from the Department of Cardiac Anesthesia, University of Ulm, Ulm, Germany.
Article Information
Pain Medicine
Pain Medicine   |   February 2002
Diffusion of Xenon and Nitrous Oxide into the Bowel during Mechanical Ileus
Anesthesiology 2 2002, Vol.96, 512-513. doi:
Anesthesiology 2 2002, Vol.96, 512-513. doi:
ONE well-known side effect of nitrous oxide is its diffusion into gas filled spaces, including the bowel. In dogs, Eger and Saidman found increased gas volumes in obstructed bowel after 4 h of 70–80% nitrous oxide anesthesia. In their study, it was speculated that the distension of the bowels and consecutive impairment of bowel perfusion could self-limit the effect of increased intraluminal pressure and thus prevent the rupture of bowels. 1 That assumption has never been tested. From a previous investigation xenon is known to diffuse into bowels to a lesser extent than nitrous oxide. Whether ileus is a contraindication for the administration of xenon could not be answered in this investigation. 2 These questions were investigated in the current study.
Materials and Methods
After approval by the Animal Care Commission, 21 pigs (German Landrace, 39.5, SD ± 2.5 kg body weight) were studied. The animals were randomly divided into three groups to receive either 75% nitrous oxide in 25% of oxygen, 75% xenon in 25% oxygen, or 75% nitrogen in 25% oxygen. Anesthesia and surgical preparations were conducted in the same manner as a previously published investigation. 2 Seventy-five milliliters of room air were injected into occluded segments of small intestine via  an inserted catheter, and intraluminal pressure was measured. Seventy-five milliliters was chosen because the pressure in the segments reached values described as clinically relevant during mechanical obstruction of bowels. 3,4 All pressures were monitored continuously and recorded every 30 min. To determine the regional specific organ perfusion, we used radiolabeled microspheres (New England Nuclear, Boston, MA, USA), administered according to the technique described by Heymann et al.  5 We used three different isotopes; Scandium 46, Strontium 85, and Niobium 95. Blood, which was used as the reference organ, was continuously withdrawn from a catheter (located in the descending aorta) at a rate of 5 ml/min over a 2 min time period. At the end of the investigation three aliquots of small intestine of each obstructed segment and of untreated areas were removed, homogenized, and placed into vials. The radioactivity was measured with a γ-ray spectrometer using a germanium (Ge) (lithium [Li]) and high purity germanium (HPGe) detector (Perkin Elmer/Ortec, Oak Ridge, TN, USA). One segment of each animal was inflated until rupture occurred. The pressure at rupture was registered.
Statistical Analysis
All data were tested for normal distribution using the Kolmogorov-Smirnov test with Lilliefors correction. Values are expressed as mean and SD or median and 25th–75th percentile according to the test results. The pressure, volume, and perfusion values of the four bowel segments were averaged for every animal at the corresponding measuring points. These mean or median values were then used for statistical comparisons. An analysis of variance (ANOVA) on ranks with Bonferroni correction for multiple comparisons was used for comparing data not normally distributed; in case of normal distribution an ANOVA and a post hoc  Dunn test were used. The results are given as P  values.
Results
No significant differences were measured for cardiac output and mean arterial blood pressures at corresponding measuring points between all groups and when comparing values of the measuring points with the initial values.
Intraluminal Pressures
Rupture of the tested bowel segments occurred at mean pressures of 115 ± 15 mmHg. Intraluminal pressures are presented in Figure 1. Compared with t 0 min, the increase was significant in all measuring points starting from t 60 min in the nitrous oxide group and in all points starting from t 60 min in the control group (P  < 0.05). No differences were found in the xenon group.
Fig. 1. Pressure kinetics during 4 h of anesthesia with xenon, nitrous oxide, or air (median: boxes = 25th–75th percentile; whiskers = 5th–95th percentile). Compared with t 0 min, differences are significant from t 60 min (#) in the nitrous oxide group and the control group (+) (P  < 0.05). No significant differences were found in the xenon group. *= significant differences compared with air (P  < 0.05).
Fig. 1. Pressure kinetics during 4 h of anesthesia with xenon, nitrous oxide, or air (median: boxes = 25th–75th percentile; whiskers = 5th–95th percentile). Compared with t 0 min, differences are significant from t 60 min (#) in the nitrous oxide group and the control group (+) (P 
	< 0.05). No significant differences were found in the xenon group. *= significant differences compared with air (P 
	< 0.05).
Fig. 1. Pressure kinetics during 4 h of anesthesia with xenon, nitrous oxide, or air (median: boxes = 25th–75th percentile; whiskers = 5th–95th percentile). Compared with t 0 min, differences are significant from t 60 min (#) in the nitrous oxide group and the control group (+) (P  < 0.05). No significant differences were found in the xenon group. *= significant differences compared with air (P  < 0.05).
×
Intraluminal Gas Volume
The content of gas volume in the nitrous oxide group (median: 140 ml, 25th–75th percentile: 132–150 ml) was significantly greater after 4 h of anesthesia compared with the control (median 67.0 ml; 65–69.5 ml;P  < 0.005) and the xenon group (median 90.0 ml; 86–93 ml;P  < 0.005). Significant differences were also found between xenon and the control (P  < 0.005).
Tissue Perfusion
No differences in perfusion rates (ml · min−1· g−1) were found in nonoccluded bowel segments. Xenon (mean ± SD) 0 min, 120 min, 240 min: 0.41 ± 0.14, 0.34 ± 0.1, 0.35 ± 0.17; nitrous oxide: 0.40 ± 0.13, 0.34 ± 0.19, 0.38 ± 0.23; control: 0.37 ± 0.19, 0.33 ± 0.09, 0.42 ± 0.12.
In occluded bowel segments the perfusion was significantly higher after 4 h in the control group compared with xenon (P  = 0.002) and nitrous oxide (P  < 0.001). No differences were found between xenon and nitrous oxide. Compared with the starting point (t 0 min), the perfusion rate was significantly higher in the control group at t 240 min (P  = 0.032), and significantly lower in nitrous oxide anesthesia at t 120 min (P  = 0.009) and t 240 min (P  = 0.002) (Fig. 2). No differences were found during xenon anesthesia.
Fig. 2. Perfusion rates at the beginning, after 2 h or 4 h of anesthesia, respectively (median; boxes = 25th–75th percentile; whiskers = 5th–95th percentile). After 4 h, there are significantly higher perfusion rates in the control group compared with xenon (*) and nitrous oxide (#). Compared with t 0 min, tissue perfusion rates were significantly greater after 4 h in the control group (P  < 0.05). In nitrous oxide anesthesia differences were significant after 120 min and 240 min (P  < 0.05). No significant differences were found in xenon anesthesia.
Fig. 2. Perfusion rates at the beginning, after 2 h or 4 h of anesthesia, respectively (median; boxes = 25th–75th percentile; whiskers = 5th–95th percentile). After 4 h, there are significantly higher perfusion rates in the control group compared with xenon (*) and nitrous oxide (#). Compared with t 0 min, tissue perfusion rates were significantly greater after 4 h in the control group (P 
	< 0.05). In nitrous oxide anesthesia differences were significant after 120 min and 240 min (P 
	< 0.05). No significant differences were found in xenon anesthesia.
Fig. 2. Perfusion rates at the beginning, after 2 h or 4 h of anesthesia, respectively (median; boxes = 25th–75th percentile; whiskers = 5th–95th percentile). After 4 h, there are significantly higher perfusion rates in the control group compared with xenon (*) and nitrous oxide (#). Compared with t 0 min, tissue perfusion rates were significantly greater after 4 h in the control group (P  < 0.05). In nitrous oxide anesthesia differences were significant after 120 min and 240 min (P  < 0.05). No significant differences were found in xenon anesthesia.
×
Discussion
Ruf et al.  observed a 70% reduction of tissue perfusion during increases of intraluminal bowel pressures reaching 60 mmHg. Surgical decompression led to a transient hyperemia of 116% of the control value. 4 In our study the reduction of perfusion in the nitrous oxide group was comparable; a mean pressure of 54 mmHg led to a reduction of the perfusion rate to 37% of the initial pressure value in the nitrous oxide group, but the resorption of gas and consecutive decompression led to a hyperemic response of 163% from the initial value in the control group. An explanation for this difference may be that the decompression process by gas resorption is a slower process compared with surgical decompression and may lead to a different mediator release. 6,7 The most important finding of our study is that in the nitrous oxide group a decrease of perfusion occurred. Our findings confirm the assumption of Eger and Saidman, who suggested that the diffusion of nitrous oxide leads to an impairment of bowel perfusion. Rupture of bowels did not occur during the investigation time. Mean pressures of 50 mmHg and maximal pressures of 82 mmHg were measured in our experiments, and were in the range of 50–75% of the maximal pressure until bowel rupture took place. Until that point a steady increase of pressure was seen with no visible departure from linearity (Fig. 1). It is possible that longer investigation times are necessary to detect decreased diffusion of nitrous oxide. No increases in bowel pressure or tissue perfusion were observed during xenon anesthesia. Xenon anesthesia could therefore be better suited for use during ileus surgery compared with nitrous oxide anesthesia.
References
Eger-EI II, Saidman LJ: Hazards of nitrous oxide anesthesia in bowel obstruction and pneumothorax. A nesthesiology 1965; 26: 61–6Eger-EI, II Saidman, LJ
Reinelt H, Schirmer U, Marx T, Topalidis P, Schmidt M: Diffusion of xenon and nitrous oxide into the bowel. A nesthesiology 2001; 94: 475–7Reinelt, H Schirmer, U Marx, T Topalidis, P Schmidt, M
Feifel G: Pathophysiology and morbidity of mechanical ileus. Langenbecks Arch Surg 1985; 366: 279–84Feifel, G
Ruf W, Suehiro GT, Suehiro A, Pressler V, McNamara JJ: Intestinal blood flow at various intraluminal pressures in the piglet with closed abdomen. Ann Surg 1980; 191: 157–63Ruf, W Suehiro, GT Suehiro, A Pressler, V McNamara, JJ
Heymann MA, Payne BD, Hoffman JIE, Rudolph AM: Blood flow measurements with radionuclide-labeled particles. Prog Cardiovasc Dis 1977; 20: 55–79Heymann, MA Payne, BD Hoffman, JIE Rudolph, AM
Mythen MG, Webb AR: The role of gut mucosal hypoperfusion in the pathogenesis of post-operative organ dysfunction. Intensive Care Med 1994; 20: 203–9Mythen, MG Webb, AR
Manasia A, Kang H, Hannon E, Lu Y, Oropello J, Leibowitz A, Stein J, Benjamin E: Effects of the stable prostacyclin analogue iloprost on mesenteric blood flow in porcine endotoxic shock. Crit Care Med 1997; 25: 1222–7Manasia, A Kang, H Hannon, E Lu, Y Oropello, J Leibowitz, A Stein, J Benjamin, E
Fig. 1. Pressure kinetics during 4 h of anesthesia with xenon, nitrous oxide, or air (median: boxes = 25th–75th percentile; whiskers = 5th–95th percentile). Compared with t 0 min, differences are significant from t 60 min (#) in the nitrous oxide group and the control group (+) (P  < 0.05). No significant differences were found in the xenon group. *= significant differences compared with air (P  < 0.05).
Fig. 1. Pressure kinetics during 4 h of anesthesia with xenon, nitrous oxide, or air (median: boxes = 25th–75th percentile; whiskers = 5th–95th percentile). Compared with t 0 min, differences are significant from t 60 min (#) in the nitrous oxide group and the control group (+) (P 
	< 0.05). No significant differences were found in the xenon group. *= significant differences compared with air (P 
	< 0.05).
Fig. 1. Pressure kinetics during 4 h of anesthesia with xenon, nitrous oxide, or air (median: boxes = 25th–75th percentile; whiskers = 5th–95th percentile). Compared with t 0 min, differences are significant from t 60 min (#) in the nitrous oxide group and the control group (+) (P  < 0.05). No significant differences were found in the xenon group. *= significant differences compared with air (P  < 0.05).
×
Fig. 2. Perfusion rates at the beginning, after 2 h or 4 h of anesthesia, respectively (median; boxes = 25th–75th percentile; whiskers = 5th–95th percentile). After 4 h, there are significantly higher perfusion rates in the control group compared with xenon (*) and nitrous oxide (#). Compared with t 0 min, tissue perfusion rates were significantly greater after 4 h in the control group (P  < 0.05). In nitrous oxide anesthesia differences were significant after 120 min and 240 min (P  < 0.05). No significant differences were found in xenon anesthesia.
Fig. 2. Perfusion rates at the beginning, after 2 h or 4 h of anesthesia, respectively (median; boxes = 25th–75th percentile; whiskers = 5th–95th percentile). After 4 h, there are significantly higher perfusion rates in the control group compared with xenon (*) and nitrous oxide (#). Compared with t 0 min, tissue perfusion rates were significantly greater after 4 h in the control group (P 
	< 0.05). In nitrous oxide anesthesia differences were significant after 120 min and 240 min (P 
	< 0.05). No significant differences were found in xenon anesthesia.
Fig. 2. Perfusion rates at the beginning, after 2 h or 4 h of anesthesia, respectively (median; boxes = 25th–75th percentile; whiskers = 5th–95th percentile). After 4 h, there are significantly higher perfusion rates in the control group compared with xenon (*) and nitrous oxide (#). Compared with t 0 min, tissue perfusion rates were significantly greater after 4 h in the control group (P  < 0.05). In nitrous oxide anesthesia differences were significant after 120 min and 240 min (P  < 0.05). No significant differences were found in xenon anesthesia.
×