FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Anesthesiology / Solubility of haloether anesthetics in human and animal bloo...
Anesthesiology2012; 117(1); 48-55; doi: 10.1097/ALN.0b013e3182557cc9

Solubility of haloether anesthetics in human and animal blood.

Abstract: Anesthetic blood solubility predicts pharmacokinetics for inhaled agents and is essential for determination of blood anesthetic concentrations from end-tidal gas concentrations using Henry's Law. Though used to model anesthetic effects in humans, there are limited interspecies solubility comparisons that include modern haloethers. This study aimed to measure hematocrit-adjusted blood:gas anesthetic partition coefficients (λ B:G) for desflurane, sevoflurane, isoflurane, and methoxyflurane in humans and animals. Methods: Whole blood was collected from 20 rats, 8 horses, and 4 each of cats, cattle, humans, dogs, goats, pigs, rabbits, and sheep. Plasma or cell volume was removed to adjust all samples to a packed cell volume of 40%. A single-agent calibration gas headspace was added to blood in a glass syringe and was mixed and equilibrated at 37°C for 2 h. Agent concentrations in the calibration gas and syringe headspace were measured using gas chromatography. Anesthetic solubility in saline, citrate-phosphate-dextrose-adenine, and olive oil were similarly measured. Results: Except for goats, all animal species had at least one λ B:G measurement that differed significantly from humans. For each agent, λ B:G positively correlated with serum triglyceride concentrations, but this only explained 25% of interspecies variability. Desflurane was significantly less soluble in blood than sevoflurane in some species (e.g., humans) but not in others (e.g., rabbits). Conclusions: Anesthetic partition coefficients differ significantly between humans and most animals for haloether anesthetics. Because of their similar λ B:G values, goats may be a better animal model for inhaled anesthetic pharmacokinetics in people.
Get Full Text
Publication Date: 2012-04-19 PubMed ID: 22510863PubMed Central: PMC3381048DOI: 10.1097/ALN.0b013e3182557cc9Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research paper investigates the predictability of pharmacokinetics for inhaled anesthetics based on their solubility in human and animal blood. It specifically examines the solubility differences of various anesthetics in different species, including humans, and suggests that goats may be most similar to humans in this regard.

Study objective and methods

  • The primary objective of the study was to ascertain the blood-to-gas anesthetic partition coefficients (λ B:G) for different anesthetics—desflurane, sevoflurane, isoflurane, and methoxyflurane in various species, including humans.
  • The researchers collected whole blood from different species, including humans, rats, horses, cats, cattle, dogs, goats, pigs, rabbits, and sheep. From these samples, they adjusted all to a packed cell volume of 40% by removing plasma or cell volume.
  • The adjusted samples were then combined with a single-agent calibration gas in a glass syringe, ensuring thorough mixing. The blend was then allowed to equilibrate at 37°C for 2 hours.
  • The concentration levels of the agent in the calibration gas and the gaseous content above (headspace) of the blood sample in the syringe were determined using gas chromatography, a measure of anesthetic solubility. This process was also repeated for saline, citrate-phosphate-dextrose-adenine, and olive oil.

Findings and Conclusion

  • The study found significant differences in λ B:G measurements between humans and almost all other animal species. The only exception was goats, which showed very similar λ B:G values to humans.
  • The research also found a positive correlation between λ B:G and serum triglyceride concentrations in the blood. However, this factor only accounted for about 25% of the interspecies variability observed.
  • The solubility of different anesthetics also varied between species. For instance, desflurane was less soluble in human blood than sevoflurane, but this was not the case in all species like rabbits.
  • The authors concluded that due to their similar λ B:G values to humans, goats might be a better animal model for studying the pharmacokinetics of inhaled anesthetics in humans.

Cite This Article

APA
Soares JH, Brosnan RJ, Fukushima FB, Hodges J, Liu H. (2012). Solubility of haloether anesthetics in human and animal blood. Anesthesiology, 117(1), 48-55. https://doi.org/10.1097/ALN.0b013e3182557cc9

Publication

Anesthesiology
ISSN: 1528-1175
NlmUniqueID: 1300217
Country: United States
Language: English
Volume: 117
Issue: 1
Pages: 48-55

Researcher Affiliations

Soares, Joao H N
  • Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Brosnan, Robert J
    Fukushima, Fabíola B
      Hodges, Joanne
        Liu, Hong

          MeSH Terms

          • Adult
          • Anesthetics, Inhalation / chemistry
          • Animals
          • Desflurane
          • Dogs
          • Erythrocyte Membrane / chemistry
          • Goats
          • Humans
          • Isoflurane / analogs & derivatives
          • Isoflurane / chemistry
          • Methoxyflurane / chemistry
          • Methyl Ethers / chemistry
          • Rabbits
          • Rats
          • Sevoflurane
          • Sheep
          • Solubility
          • Swine

          Grant Funding

          • R01 GM092821 / NIGMS NIH HHS
          • R01 GM092821-01A1 / NIGMS NIH HHS
          • GM092821-02 / NIGMS NIH HHS

          References

          This article includes 66 references
          1. Berthelot MPE, Jungfleisch ÉC. Sur les lois qui président au partage d’un corps entre deux dissolvants (expériences). Ann Chim Phys 1872;26:396–407.
          2. Eger EI 2nd, Johnson BH. Do volatile anesthetics act as ideal gases?. Anesth Analg 1979 Jul-Aug;58(4):322-3.
            pubmed: 572178doi: 10.1213/00000539-197907000-00013google scholar: lookup
          3. Coburn CM, Eger EI 2nd. The partial pressure of isoflurane or halothane does not affect their solubility in rabbit blood or brain or human brain: inhaled anesthetics obey Henry's Law.. Anesth Analg 1986 Sep;65(9):960-2.
            pubmed: 3740495
          4. Lockhart SH, Eger EI 2nd. Absence of abundant saturable binding sites for halothane or isoflurane in rabbit brain: inhaled anesthetics obey Henry's law.. Anesth Analg 1990 Jul;71(1):70-2.
            pubmed: 2363532doi: 10.1213/00000539-199007000-00012google scholar: lookup
          5. Overton CE. Studies of Narcosis. Chapman and Hall; London: 1991.
          6. Fang Z, Ionescu P, Chortkoff BS, Kandel L, Sonner J, Laster MJ, Eger EI 2nd. Anesthetic potencies of n-alkanols: results of additivity and solubility studies suggest a mechanism of action similar to that for conventional inhaled anesthetics.. Anesth Analg 1997 May;84(5):1042-8.
            pubmed: 9141929doi: 10.1097/00000539-199705000-00017google scholar: lookup
          7. Eger EI. Anesthetic Uptake and Action. Williams & Wilkins; Baltimore: 1974.
          8. Lockwood GG, Sapsed-Byrne SM, Smith MA. Effect of temperature on the solubility of desflurane, sevoflurane, enflurane and halothane in blood.. Br J Anaesth 1997 Oct;79(4):517-20.
            pubmed: 9389273doi: 10.1093/bja/79.4.517google scholar: lookup
          9. Stoelting RK, Longshore RE. The effects of temperature on fluroxene, halothane, and methoxyflurane blood--gas and cerebrospinal fluid--gas partition coefficients.. Anesthesiology 1972 May;36(5):503-5.
            pubmed: 4401803doi: 10.1097/00000542-197205000-00018google scholar: lookup
          10. Eger RR, Eger EI 2nd. Effect of temperature and age on the solubility of enflurane, halothane, isoflurane, and methoxyflurane in human blood.. Anesth Analg 1985 Jun;64(6):640-2.
            pubmed: 4003781
          11. Allott PR, Steward A, Flook V, Mapleson WW. Variation with temperature of the solubilities of inhaled anaesthetics in water, oil and biological media.. Br J Anaesth 1973 Mar;45(3):294-300.
            pubmed: 4573001doi: 10.1093/bja/45.3.294google scholar: lookup
          12. Lerman J, Gregory GA, Eger EI 2nd. Hematocrit and the solubility of volatile anesthetics in blood.. Anesth Analg 1984 Oct;63(10):911-4.
            pubmed: 6486490
          13. Pang YC, Reid PE, Brooks DE. Solubility and distribution of halothane in human blood.. Br J Anaesth 1980 Sep;52(9):851-62.
            pubmed: 6159909doi: 10.1093/bja/52.9.851google scholar: lookup
          14. Lerman J, Gregory GA, Willis MM, Eger EI 2nd. Age and solubility of volatile anesthetics in blood.. Anesthesiology 1984 Aug;61(2):139-43.
            pubmed: 6465597doi: 10.1097/00000542-198408000-00005google scholar: lookup
          15. Lerman J, Willis MM, Gregory GA, Eger EI 2nd. Osmolarity determines the solubility of anesthetics in aqueous solutions at 37 degrees C.. Anesthesiology 1983 Dec;59(6):554-8.
            pubmed: 6418030doi: 10.1097/00000542-198312000-00013google scholar: lookup
          16. Saraiva RA, Willis BA, Steward A, Lunn JN, Mapleson WW. Halothane solubility in human blood.. Br J Anaesth 1977 Feb;49(2):115-9.
            pubmed: 836744doi: 10.1093/bja/49.2.115google scholar: lookup
          17. Weaver BM, Webb AI. Tissue composition and halothane solubility in the horse.. Br J Anaesth 1981 May;53(5):487-93.
            pubmed: 7236473doi: 10.1093/bja/53.5.487google scholar: lookup
          18. LARSON CP Jr, EGER EI 2nd, SEVERINGHAUS JW. The solubility of halothane in blood and tissue homogenates.. Anesthesiology 1962 May-Jun;23:349-55.
            pubmed: 14462522doi: 10.1097/00000542-196205000-00009google scholar: lookup
          19. Ludbrook J. Multiple comparison procedures updated.. Clin Exp Pharmacol Physiol 1998 Dec;25(12):1032-7.
            pubmed: 9888002doi: 10.1111/j.1440-1681.1998.tb02179.xgoogle scholar: lookup
          20. Saidman LJ, Eger EI 2nd, Munson ES, Babad AA, Muallem M. Minimum alveolar concentrations of methoxyflurane, halothane, ether and cyclopropane in man: correlation with theories of anesthesia.. Anesthesiology 1967 Nov-Dec;28(6):994-1002.
            pubmed: 6058074doi: 10.1097/00000542-196711000-00009google scholar: lookup
          21. Stevens WC, Dolan WM, Gibbons RT, White A, Eger EI, Miller RD, DeJong RH, Elashoff RM. Minimum alveolar concentrations (MAC) of isoflurande with and without nitrous oxide in patients of various ages.. Anesthesiology 1975 Feb;42(2):197-200.
            pubmed: 1115370doi: 10.1097/00000542-197502000-00014google scholar: lookup
          22. Scheller MS, Saidman LJ, Partridge BL. MAC of sevoflurane in humans and the New Zealand white rabbit.. Can J Anaesth 1988 Mar;35(2):153-6.
            pubmed: 3356052doi: 10.1007/bf03010656google scholar: lookup
          23. Rampil IJ, Lockhart SH, Zwass MS, Peterson N, Yasuda N, Eger EI 2nd, Weiskopf RB, Damask MC. Clinical characteristics of desflurane in surgical patients: minimum alveolar concentration.. Anesthesiology 1991 Mar;74(3):429-33.
            pubmed: 2001020doi: 10.1097/00000542-199103000-00007google scholar: lookup
          24. Koblin DD, Laster MJ, Ionescu P, Gong D, Eger EI 2nd, Halsey MJ, Hudlicky T. Polyhalogenated methyl ethyl ethers: solubilities and anesthetic properties.. Anesth Analg 1999 May;88(5):1161-7.
            pubmed: 10320188doi: 10.1097/00000539-199905000-00036google scholar: lookup
          25. EGER EI 2nd, SHARGEL R. THE SOLUBILITY OF METHOXYFLURANE IN HUMAN BLOOD AND TISSUE HOMOGENATES.. Anesthesiology 1963 Sep-Oct;24:625-7.
            pubmed: 14063759doi: 10.1097/00000542-196309000-00006google scholar: lookup
          26. Hendrickx JF, Lemmens HJ, Carette R, De Wolf AM, Saidman LJ. Can Modern Infrared Analyzers Replace Gas Chromatography to Measure Anesthetic Vapor Concentrations?. BMC Anesthesiol 2008 Feb 8;8:2.
            pmc: PMC2259326pubmed: 18261229doi: 10.1186/1471-2253-8-2google scholar: lookup
          27. Carpenter RL, Eger EI 2nd, Johnson BH, Unadkat JD, Sheiner LB. Pharmacokinetics of inhaled anesthetics in humans: measurements during and after the simultaneous administration of enflurane, halothane, isoflurane, methoxyflurane, and nitrous oxide.. Anesth Analg 1986 Jun;65(6):575-82.
            pubmed: 3706798
          28. Grob RL, Kaiser MA, Grob RL, Barry EF. Qualitative and quantitative analysis by gas chromatography. Modern Practice of Gas Chromatography. 4th Edition John Wiley & Sons; Hoboken, NJ: 2004. pp. 403–460.
          29. Taheri S, Halsey MJ, Liu J, Eger EI 2nd, Koblin DD, Laster MJ. What solvent best represents the site of action of inhaled anesthetics in humans, rats, and dogs?. Anesth Analg 1991 May;72(5):627-34.
            pubmed: 2018220doi: 10.1213/00000539-199105000-00010google scholar: lookup
          30. Yu RG, Zhou JX, Liu J. Prediction of volatile anaesthetic solubility in blood and priming fluids for extracorporeal circulation.. Br J Anaesth 2001 Mar;86(3):338-44.
            pubmed: 11573521doi: 10.1093/bja/86.3.338google scholar: lookup
          31. Scheller MS, Saidman LJ, Partridge BL. MAC of sevoflurane in humans and the New Zealand white rabbit.. Can J Anaesth 1988 Mar;35(2):153-6.
            pubmed: 3356052doi: 10.1007/bf03010656google scholar: lookup
          32. Doorley BM, Waters SJ, Terrell RC, Robinson JL. MAC of I-653 in beagle dogs and New Zealand white rabbits.. Anesthesiology 1988 Jul;69(1):89-91.
            pubmed: 3389568doi: 10.1097/00000542-198807000-00013google scholar: lookup
          33. Yasuda N, Lockhart SH, Eger EI 2nd, Weiskopf RB, Johnson BH, Freire BA, Fassoulaki A. Kinetics of desflurane, isoflurane, and halothane in humans.. Anesthesiology 1991 Mar;74(3):489-98.
            pubmed: 2001028doi: 10.1097/00000542-199103000-00017google scholar: lookup
          34. Lam CW, Galen TJ, Boyd JF, Pierson DL. Mechanism of transport and distribution of organic solvents in blood.. Toxicol Appl Pharmacol 1990 Jun 1;104(1):117-29.
            pubmed: 2360202doi: 10.1016/0041-008x(90)90287-5google scholar: lookup
          35. Clerbaux T, Gustin P, Detry B, Cao ML, Frans A. Comparative study of the oxyhaemoglobin dissociation curve of four mammals: man, dog, horse and cattle.. Comp Biochem Physiol Comp Physiol 1993 Dec;106(4):687-94.
            pubmed: 7906628doi: 10.1016/0300-9629(93)90382-egoogle scholar: lookup
          36. Poyart C, Wajcman H, Kister J. Molecular adaptation of hemoglobin function in mammals.. Respir Physiol 1992 Oct;90(1):3-17.
            pubmed: 1455096doi: 10.1016/0034-5687(92)90130-ogoogle scholar: lookup
          37. Giardina B, Brix O, Clementi ME, Scatena R, Nicoletti B, Cicchetti R, Argentin G, Condo SG. Differences between horse and human haemoglobins in effects of organic and inorganic anions on oxygen binding.. Biochem J 1990 Mar 15;266(3):897-900.
            pmc: PMC1131223pubmed: 2327974
          38. Dresler SL, Runkel D, Stenzel P, Brimhall B, Jones RT. Multiplicity of the hemoglobin alpha chains in dogs and variations among related species.. Ann N Y Acad Sci 1974 Nov 29;241(0):411-5.
            pubmed: 4530667doi: 10.1111/j.1749-6632.1974.tb21896.xgoogle scholar: lookup
          39. Eckenhoff RG, Johansson JS. Molecular interactions between inhaled anesthetics and proteins.. Pharmacol Rev 1997 Dec;49(4):343-67.
            pubmed: 9443162
          40. Schoenborn BP. Binding of xenon to horse haemoglobin.. Nature 1965 Nov 20;208(5012):760-2.
            pubmed: 5868886doi: 10.1038/208760a0google scholar: lookup
          41. Nelson GJ. Lipid composition of erythrocytes in various mammalian species.. Biochim Biophys Acta 1967 Oct 2;144(2):221-32.
            pubmed: 6064604doi: 10.1016/0005-2760(67)90152-xgoogle scholar: lookup
          42. Kwan E, Trevor A. The association of xenon with subcellular components of rat cerebral cortex.. Mol Pharmacol 1969 May;5(3):236-43.
            pubmed: 5783959
          43. Kosa T, Maruyama T, Otagiri M. Species differences of serum albumins: I. Drug binding sites.. Pharm Res 1997 Nov;14(11):1607-12.
            pubmed: 9434282doi: 10.1023/a:1012138604016google scholar: lookup
          44. Pang YC, Reid PE, Brooks DE. Solubility and distribution of halothane in human blood.. Br J Anaesth 1980 Sep;52(9):851-62.
            pubmed: 6159909doi: 10.1093/bja/52.9.851google scholar: lookup
          45. Laasberg LH, Hedley-Whyte J. Halothane solubility in blood and solutions of plasma proteins: effects of temperature, protein composition and hemoglobin concentration.. Anesthesiology 1970 Apr;32(4):351-6.
            pubmed: 5437865doi: 10.1097/00000542-197004000-00010google scholar: lookup
          46. Eckenhoff RG. Amino acid resolution of halothane binding sites in serum albumin.. J Biol Chem 1996 Jun 28;271(26):15521-6.
            pubmed: 8663164doi: 10.1074/jbc.271.26.15521google scholar: lookup
          47. Johansson JS, Eckenhoff RG, Dutton PL. Binding of halothane to serum albumin demonstrated using tryptophan fluorescence.. Anesthesiology 1995 Aug;83(2):316-24.
            pubmed: 7631954doi: 10.1097/00000542-199508000-00012google scholar: lookup
          48. Liu R, Eckenhoff RG. Weak polar interactions confer albumin binding site selectivity for haloether anesthetics.. Anesthesiology 2005 Apr;102(4):799-805.
            pubmed: 15791110doi: 10.1097/00000542-200504000-00016google scholar: lookup
          49. Eger EI 2nd. Partition coefficients of I-653 in human blood, saline, and olive oil.. Anesth Analg 1987 Oct;66(10):971-3.
            pubmed: 3631593
          50. Zhou JX, Liu J. Dynamic changes in blood solubility of desflurane, isoflurane, and halothane during cardiac surgery.. J Cardiothorac Vasc Anesth 2001 Oct;15(5):555-9.
            pubmed: 11687993doi: 10.1053/jcan.2001.26529google scholar: lookup
          51. Wallin RF, Regan BM, Napoli MD, Stern IJ. Sevoflurane: a new inhalational anesthetic agent.. Anesth Analg 1975 Nov-Dec;54(6):758-66.
            pubmed: 1239214doi: 10.1213/00000539-197511000-00021google scholar: lookup
          52. Strum DP, Eger EI 2nd. Partition coefficients for sevoflurane in human blood, saline, and olive oil.. Anesth Analg 1987 Jul;66(7):654-6.
            pubmed: 3605675
          53. Cromwell TH, Eger EI 2nd, Stevens WC, Dolan WM. Forane uptake, excretion, and blood solubility in man.. Anesthesiology 1971 Oct;35(4):401-8.
            pubmed: 5114401doi: 10.1097/00000542-197110000-00017google scholar: lookup
          54. Lerman J, Gregory GA, Eger EI 2nd. Hematocrit and the solubility of volatile anesthetics in blood.. Anesth Analg 1984 Oct;63(10):911-4.
            pubmed: 6486490
          55. Bergadano A, Lauber R, Zbinden A, Schatzmann U, Moens Y. Blood/gas partition coefficients of halothane, isoflurane and sevoflurane in horse blood.. Br J Anaesth 2003 Aug;91(2):276-8.
            pubmed: 12878628doi: 10.1093/bja/aeg151google scholar: lookup
          56. Lerman J, Gregory GA, Willis MM, Schmitt BI, Eger EI 2nd. Age and the solubility of volatile anesthetics in ovine tissues.. Anesth Analg 1985 Nov;64(11):1097-100.
            pubmed: 4051207
          57. Zhou JX, Liu J. Tissue solubility of four volatile anesthetics in fresh and frozen tissue specimens from swine.. Am J Vet Res 2002 Jan;63(1):74-7.
            pubmed: 16206784doi: 10.2460/ajvr.2002.63.74google scholar: lookup
          58. Yasuda N, Targ AG, Eger EI 2nd, Johnson BH, Weiskopf RB. Pharmacokinetics of desflurane, sevoflurane, isoflurane, and halothane in pigs.. Anesth Analg 1990 Oct;71(4):340-8.
            pubmed: 2400116doi: 10.1213/00000539-199010000-00004google scholar: lookup
          59. Zbinden AM, Frei FJ, Funk B, Thomson DA, Westenskow D. Determination of the partial pressure of halothane (or isoflurane) in blood.. Br J Anaesth 1985 Aug;57(8):796-802.
            pubmed: 4015939doi: 10.1093/bja/57.8.796google scholar: lookup
          60. Holdcroft A, Bose D, Sapsed-Byrne SM, Ma D, Lockwood GG. Arterial to inspired partial pressure ratio of halothane, isoflurane, sevoflurane and desflurane in rats.. Br J Anaesth 1999 Oct;83(4):618-21.
            pubmed: 10673881doi: 10.1093/bja/83.4.618google scholar: lookup
          61. Rao Y, Wang YL, Li H, Zhang W, Liu J. Effects of pregnancy on the solubility of halogenated volatile anaesthetics in rat blood and tissues.. Anaesth Intensive Care 2008 Nov;36(6):830-4.
            pubmed: 19115652doi: 10.1177/0310057x0803600612google scholar: lookup
          62. Stern RC, Towler SC, White PF, Evers AS. Elimination kinetics of sevoflurane and halothane from blood, brain, and adipose tissue in the rat.. Anesth Analg 1990 Dec;71(6):658-64.
            pubmed: 2240639doi: 10.1213/00000539-199012000-00014google scholar: lookup
          63. Gargas ML, Burgess RJ, Voisard DE, Cason GH, Andersen ME. Partition coefficients of low-molecular-weight volatile chemicals in various liquids and tissues.. Toxicol Appl Pharmacol 1989 Mar 15;98(1):87-99.
            pubmed: 2929023doi: 10.1016/0041-008x(89)90137-3google scholar: lookup
          64. Fassoulaki A, Eger EI 2nd. Starvation increases the solubility of volatile anaesthetics in rat liver.. Br J Anaesth 1986 Mar;58(3):327-9.
            pubmed: 3947496doi: 10.1093/bja/58.3.327google scholar: lookup
          65. Hönemann CW, Washington J, Hönemann MC, Nietgen GW, Durieux ME. Partition coefficients of volatile anesthetics in aqueous electrolyte solutions at various temperatures.. Anesthesiology 1998 Oct;89(4):1032-5.
            pubmed: 9778025doi: 10.1097/00000542-199810000-00032google scholar: lookup
          66. Koblin DD, Eger EI 2nd, Johnson BH, Collins P, Harper MH, Terrell RC, Speers L. Minimum alveolar concentrations and oil/gas partition coefficients of four anesthetic isomers.. Anesthesiology 1981 Apr;54(4):314-7.
            pubmed: 6782912doi: 10.1097/00000542-198104000-00011google scholar: lookup

          Citations

          This article has been cited 9 times.
          1. Williams CJA, Malte CL, Malte H, Bertelsen MF, Wang T. Ectothermy and cardiac shunts profoundly slow the equilibration of inhaled anaesthetics in a multi-compartment model. Sci Rep 2020 Oct 13;10(1):17157.
            doi: 10.1038/s41598-020-74014-ypubmed: 33051496google scholar: lookup
          2. Zhang P, Li Y, Xu T. Development of a simple method for differential delivery of volatile anesthetics to the spinal cord of the rabbit. PLoS One 2020;15(2):e0223700.
            doi: 10.1371/journal.pone.0223700pubmed: 32092080google scholar: lookup
          3. Maier KL, McKinstry-Wu AR, Palanca BJA, Tarnal V, Blain-Moraes S, Basner M, Avidan MS, Mashour GA, Kelz MB. Protocol for the Reconstructing Consciousness and Cognition (ReCCognition) Study. Front Hum Neurosci 2017;11:284.
            doi: 10.3389/fnhum.2017.00284pubmed: 28638328google scholar: lookup
          4. Brosnan RJ, Fukushima FB, Pham TL. Anesthetic synergy between two n-alkanes. Vet Anaesth Analg 2017 May;44(3):577-588.
            doi: 10.1016/j.vaa.2016.07.003pubmed: 28583773google scholar: lookup
          5. Ye BO, Ji Y, Yuan Q, Zhang GR, Fan Q, Wei G, Yin Z, Tao L. Sevoflurane inhibits the antioxidant capacity of erythrocytes. Exp Ther Med 2016 Feb;11(2):650-654.
            doi: 10.3892/etm.2015.2938pubmed: 26893661google scholar: lookup
          6. Becker LF, Schwarz DH, Wenz G. Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs. Beilstein J Org Chem 2014;10:2920-7.
            doi: 10.3762/bjoc.10.310pubmed: 25550759google scholar: lookup
          7. Brosnan RJ. Inhaled anesthetics in horses. Vet Clin North Am Equine Pract 2013 Apr;29(1):69-87.
            doi: 10.1016/j.cveq.2012.11.006pubmed: 23498046google scholar: lookup
          8. Bader M, Roßbach B, Göen T, Eckert E, Schäferhenrich A, Nübler S, Gries W, Leng G, Van Pul J, Will W, Hartwig A. Die gaschromatographische Dampfraumanalyse im Human-Biomonitoring (Headspace-Gaschromatographie): Biomonitoring-Methoden, Konzeptionelle Themen. MAK Collect Occup Health Saf 2025;10(3):Doc056.
            doi: 10.34865/bihsgcdgt10_3orpubmed: 41584498google scholar: lookup
          9. Bader M, Roßbach B, Göen T, Eckert E, Schäferhenrich A, Nübler S, Gries W, Leng G, Van Pul J, Will W, Hartwig A. Gas-chromatographic headspace analysis in human biomonitoring (headspace-gas chromatography): Biomonitoring Methods, Conceptual Topics - Translation of the German version from 2025. MAK Collect Occup Health Saf 2025;10(3):Doc057.
            doi: 10.34865/bihsgcegt10_3orpubmed: 41584497google scholar: lookup
          Subscribe to our newsletter
          Join 99,001 horse owners like you who receive our email updates on horse health and nutrition.