Cardiac output and the pharmacology of general anesthetics: a narrative review
Abstract
The relationship between cardiac output and anesthetic drugs is important to anesthesiologists, since cardiac output determines the speed with which a drug infused into the bloodstream reaches its target and the intensity of the drug’s effect. But rather than focus on how anesthetic drugs affect cardiac output, this narrative review focuses on how changes in cardiac output affect the pharmacokinetics and pharmacodynamics of general anesthetics during the three phases of anesthesia.
At induction, an increase in cardiac output shortens both the onset time of propofol for hypnosis and the neuromuscular blocking effect of rapid-acting neuromuscular blockers, favoring the conditions for rapid sequence intubation.
During maintenance, changes in cardiac output are followed by opposite changes in the drug plasma concentration of anesthetic drugs. Thus, an increase in cardiac output followed by a decrease in the plasma concentration of the anesthetic could expose the patient to a real risk of intraoperative awakening, which can be avoided by increasing the dose of hypnotic drugs.
At emergence, an increase in cardiac output secondary to an increase in pCO2 allows for a more rapid recovery from anesthesia. The pCO2 can be increased by adding CO2 to the respiratory circuit, lowering the ventilatory rate, or placing the patient on partial rebreathing. Finally, the reversal action of sugammadex for rocuronium-induced neuromuscular block can be shortened by increasing the cardiac output.
References
De Wit F, Van Vliet AL, De Wilde RB, Jansen JR, Vuyk J, Aarts LP, et al. The effect of propofol on haemodynamics: Cardiac output, venous return, mean systemic filling pressure, and vascular resistances. Br J Anaesth. 2016;116(6):784–9. doi: https://doi.org/10.1093/bja/aew126
Masui K, Upton RN, Doufas AG, Coetzee JF, Kazama T, Mortier EP, et al. The performance of compartmental and physiologically based recirculatory pharmacokinetic models for propofol: A comparison using bolus, continuous, and target-controlled infusion data. Anesth Analg. 2010;111(2):368–79. doi: https://doi.org/10.1213/ANE.0b013e3181bdcf5b
Krejcie T, Avram M. What determines anesthetic induction dose? It’s the front-end kinetics, doctor! Anesth Analg. 1999;89(3):541–4. doi: https://doi.org/10.1097/00000539-199909000-00001
Fisher DM. (Almost) everything you learned about pharmacokinetics was (somewhat) wrong! Anesth Analg. 1996;83(5):901–3. doi: https://doi.org/10.1097/00000539-199611000-00002
Upton RN, Huang YF. Influence of cardiac output, injection time and injection volume on the initial mixing of drugs with venous blood after i.v. bolus administration to sheep. Br J Anaesth. 1993;70(3):333–8. doi: https://doi.org/10.1093/bja/70.3.333
Upton RN. The two-compartment recirculatory pharmacokinetic model - An introduction to recirculatory pharmacokinetic concepts. Br J Anaesth. 2004;92(4):475–84. doi: https://doi.org/10.1093/bja/aeh089
Kuipers JA, Boer F, Olofsen E, Bovill JG, Burm AG. Recirculatory pharmacokinetics and pharmacodynamics of rocuronium in patients: The influence of cardiac output. Anesthesiology. 2001;94(1):47–55. doi: https://doi.org/10.1097/00000542-200101000-00012
Avram MJ, Krejcie TC, Henthorn TK, Niemann CU. β-adrenergic blockade affects initial drug distribution due to decreased cardiac output and altered blood flow distribution. J Pharmacol Exp Ther. 2004;311(2):617–24. doi: https://doi.org/10.1124/jpet.104.070094
Szmuk P, Ezri T, Chelly JE, Katz J. The onset time of rocuronium is slowed by esmolol and accelerated by ephedrine. Anesth Analg. 2000;90(5):1217–9. doi: https://doi.org/10.1097/00000539-200005000-00041
Myburgh JA, Upton RN, Grant C, Martinez A. Epinephrine, norepinephrine and dopamine infusions decrease propofol concentrations during continuous propofol infusion in an ovine model. Intensive Care Med. 2001;27(1):276–82. doi: https://doi.org/10.1007/s001340000793
Kurita T, Morita K, Kazama T, Sato S. Influence of cardiac output on plasma propofol concentrations during constant infusion in swine. Anesthesiology. 2002;96(6):1498–503. doi: https://doi.org/10.1097/00000542-200206000-00033
Ezri T, Szmuk P, Warters RD, Gebhard RE, Pivalizza EG, Katz J. Changes in onset time of rocuronium in patients pretreated with ephedrine and esmolol - The role of cardiac output. Acta Anaesthesiol Scand. 2003;47(9):1067–72. doi: https://doi.org/10.1034/j.1399-6576.2003.00218.x
Wilson ES, McKinlay S, Crawford JM, Robb HM. The influence of esmolol on the dose of propofol required for induction of anaesthesia. Anaesthesia. 2004;59(2):122–6. doi: https://doi.org/10.1111/j.1365-2044.2004.03460.x
Gras S, Servin F, Bedairia E, Montravers P, Desmonts JM, Longrois D, et al. The effect of preoperative heart rate and anxiety on the propofol dose required for loss of consciousness. Anesth Analg. 2010;110(1):89–93. doi: https://doi.org/10.1213/ANE.0b013e3181c5bd11
Adachi YU, Watanabe K, Higuchi H, Satoh T. The determinants of propofol induction of anesthesia dose. Anesth Analg. 2001;92(3):656–61. doi: https://doi.org/10.1097/00000539-200103000-00020
Katznelson R, Minkovich L, Friedman Z, Fedorko L, Beattie WS, Fisher JA. Accelerated recovery from sevoflurane anesthesia with isocapnic hyperpnoea. Anesth Analg. 2008;106(2):486–91. doi: https://doi.org/10.1213/ane.0b013e3181602dd4
Ghosh I, Bithal PK, Dash HH, Chaturvedi A, Prabhakar H. Both clonidine and metoprolol modify anesthetic depth indicators and reduce intraoperative propofol requirement. J Anesth. 2008;22(2):131–4. doi: https://doi.org/10.1007/s00540-007-0606-y
Sastre J, López T, Gómez-Ríos M, Garzón JC, Mariscal ML, Martínez-Hurtado E, et al; ISR Study Group. [Current practice of rapid sequence induction in adults: A national survey among anesthesiologists in Spain]. Rev Esp Anestesiol Reanim. 2020;67(7):381–90. doi: https://doi.org/10.1016/j.redar.2020.03.007
Upton RN, Ludbrook GL. A physiological model of induction of anaesthesia with propofol in sheep. 1. Structure and estimation of variables. Br J Anaesth. 1997;79(4):497–504. doi: https://doi.org/10.1093/bja/79.4.497
Ludbrook GL, Upton RN. A physiological model of induction of anaesthesia with propofol in sheep. 2. Model analysis and implications for dose requirements. Br J Anaesth. 1997;79(4):505–13. doi: https://doi.org/10.1093/bja/79.4.505
Upton RN, Ludbrook GL, Grant C, Martinez AM. Cardiac output is a determinant of the initial concentrations of propofol after short-infusion administration. Anesth Analg. 1999;89(3):545–52. doi: https://doi.org/10.1097/00000539-199909000-00002
Takizawa E, Takizawa D, Al-Jahdari WS, Miyazaki M, Nakamura K, Yamamoto K, et al. Influence of atropine on the dose requirements of propofol in humans. Drug Metab Pharmacokinet. 2006;21(5):384–8. doi: https://doi.org/10.2133/dmpk.21.384
Maranets I, Kain Z. Preoperative anxiety and intraoperative anesthetic requirements. Anesth Analg. 1999;89(6):1346–51. doi: https://doi.org/10.1097/00000539-199912000-00003
Muñoz H, González A, Dagnino J, González JA, Pérez AE. The effect of ephedrine on the onset time of rocuronium. Anesth Analg. 1997;85(2):437–40. doi: https://doi.org/10.1097/00000539-199708000-00034
Harrison GA, Junius F. The effect of circulation time on the neuromuscular action of suxamethonium. Anaesth Intensive Care. 1972;1(1):33–40. doi: https://doi.org/10.1177/0310057X7200100103
Ganidagli S, Cengiz M, Baysal Z. Effect of ephedrine on the onset time of succinylcholine. Acta Anaesthesiol Scand. 2004;48(10):1306–9. doi: https://doi.org/10.1111/j.1399-6576.2004.00529.x
Belyamani L, Azendour H, Elhassouni A, Zidouh S, Atmani M, Kamili ND. [Effect of ephedrine on the intubation conditions using rocuronium versus succinylcholine]. Ann Fr Anesth Reanim. 2008;27(4):292–6. French. doi: https://doi.org/10.1016/j.annfar.2007.12.016
Gopalakrishna MD, Krishna HM, Shenoy UK. The effect of ephedrine on intubating conditions and haemodynamics during rapid tracheal intubation using propofol and rocuronium. Br J Anaesth. 2007;99(2):191–4. doi: https://doi.org/10.1093/bja/aem125
Han DW, Chun DH, Kweon TD, Shin YS. Significance of the injection timing of ephedrine to reduce the onset time of rocuronium. Anaesthesia. 2008;63(8):856–60. doi: https://doi.org/10.1111/j.1365-2044.2008.05497.x
Santiveri X, Mansilla R, Pardina B, Navarro J, Alvarez JC, Castillo J. Ephedrine shortens the onset of action of rocuronium but not of atracurium. Rev Esp Anestesiol Reanim. 2003;50(4):176–81.
Komatsu R, Nagata O, Ozaki M, Sessler DI. Ephedrine fails to accelerate the onset of neuromuscular block by vecuronium. Anesth Analg. 2003;97(2):480–3. doi: https://doi.org/10.1213/01.ANE.0000069212.49766.7A
Kim KS, Cheong MA, Jeon JW, Lee JH, Shim JC. The dose effect of ephedrine on the onset time of vecuronium. Anesth Analg. 2003;96(4):1042–6. doi: https://doi.org/10.1213/01.ANE.0000034551.93647.3A
Anandan K, Suseela I, Purayil H. Comparison of effect of ephedrine and priming on the onset time of vecuronium. Anesth Essays Res. 2017;11(2):421–5. doi: https://doi.org/10.4103/0259-1162.194582
Albert F, Hans P, Bitar Y, Brichant JF, Dewandre PY, Lamy M. Effects of ephedrine on the onset time of neuromuscular block and intubating conditions after cisatracurium: preliminary results. Acta Anaesthesiol Belg. 2000;51(3):167–71.
Leykin Y, Dalsasso M, Setti T, Pelis T. The effects of low-dose ephedrine on intubating conditions following low-dose priming with cisatracurium. J Clin Anesth. 2010;22(6):425–31. doi: https://doi.org/10.1016/j.jclinane.2009.10.016
Cha DG, Kim KS, Jeong JS, Kwon HM. The dose effect of ephedrine on the onset time and intubating conditions after cisatracurium administration. Korean J Anesthesiol. 2014;67(1):26–31. doi: https://doi.org/10.4097/kjae.2014.67.1.26
Sun R, Tian JH, Li L, Tian HL, Jia WQ, Yang KH, et al. Effect of ephedrine on intubating conditions created by propofol and rocuronium: A meta-analysis. J Evid Based Med. 2012;5(4):209–15. doi: https://doi.org/10.1111/jebm.12003
Dong J, Gao L, Lu W, Xu Z, Zheng J. Pharmacological interventions for acceleration of the onset time of rocuronium: A meta-analysis. PLoS One. 2014;9(12):e114231. doi: https://doi.org/10.1371/journal.pone.0114231
Kurita T, Uraoka M, Jiang Q, Suzuki M, Morishima Y, Morita K, et al. Influence of cardiac output on the pseudo-steady state remifentanil and propofol concentrations in swine. Acta Anaesthesiol Scand. 2013;57(6):754–60. doi: https://doi.org/10.1111/aas.12076
Takizawa D, Nishikawa K, Sato E, Hiraoka H, Yamamoto K, Saito S, et al. A dopamine infusion decreases propofol concentration during epidural blockade under general anesthesia. Can J Anesth. 2005;52(5):463–6. doi: https://doi.org/10.1007/BF03016523
O’Neill DK, Aizer A, Linton P, Bloom M, Rose E, Chinitz L. Isoproterenol infusion increases level of consciousness during catheter ablation of atrial fibrillation. J Interv Card Electrophysiol. 2012;34(2):137–42. doi: https://doi.org/10.1007/s10840-011-9652-3
Ishiyama T, Oguchi T, Iijima T, Matsukawa T, Kashimoto S, Kumazawa T. Ephedrine, but not phenylephrine, increases bispectral index values during combined general and epidural anesthesia. Anesth Analg. 2003;97(3):780–4. doi: https://doi.org/10.1213/01.ANE.0000073355.63287.E4
Moon YE, Hwang WJ, Koh HJ, Min JY LJ. The sparing effect of low-dose esmolol on sevoflurane during laparoscopic gynaecological surgery. J Int Med Res. 2011;39(5):1861–9. doi: https://doi.org/10.1177/147323001103900529
Bienert A, Sobczyński P, Młodawska K, Hartmann-Sobczyńska R, Grześkowiak E, Wiczling P. The influence of cardiac output on propofol and fentanyl pharmacokinetics and pharmacodynamics in patients undergoing abdominal aortic surgery. J Pharmacokinet Pharmacodyn. 2020;47(6):583–96. doi: https://doi.org/10.1007/s10928-020-09712-1
Matthews R. Isoproterenol-induced elevated bispectral indexes while undergoing radiofrequency ablation: A case report. AANA J. 2006;74(3):193–5.
Catalá Ripoll JV, Hidalgo-Olivares VM, Monsalve-Naharro JÁ, Gerónimo-Pardo M. Intraoperative awareness as an example of the influence of cardiac output on anesthetic dosing: case report. Rev Colomb Anestesiol. 2018;46(4):341–4. doi: http://dx.doi.org/10.1097/CJ9.0000000000000063
Crystal GJ. Carbon dioxide and the heart: Physiology and clinical implications. Anesth Analg. 2015;121(3):610–23. doi: https://doi.org/10.1213/ANE.0000000000000820
Sakata DJ, Gopalakrishnan NA, Orr JA, White JL, Westenskow DR. Hypercapnic hyperventilation shortens emergence time from isoflurane anesthesia. Anesth Analg. 2007;104(3):587–91. doi: https://doi.org/10.1213/01.ane.0000255074.96657.39
Vesely A, Fisher JA, Sasano N, Preiss D, Somogyi R, El-Beheiry H, et al. Isocapnic hyperpnoea accelerates recovery from isoflurane anaesthesia. Br J Anaesth. 2003;91(6):787–92. doi: https://doi.org/10.1093/bja/aeg269
Yaraghi A, Golparvar M, Talakoub R, Sateie H, Mehrabi A. Hypercapnic hyperventilation shortens emergence time from propofol and isoflurane anesthesia. J Res Pharm Pract. 2013;2(1):24–8. doi: https://doi.org/10.4103/2279-042X.114085
Brosnan RJ, Steffey EP, Escobar A. Effects of hypercapnic hyperpnea on recovery from isoflurane or sevoflurane anesthesia in horses. Vet Anaesth Analg. 2012;39(4):335–44. doi: https://doi.org/10.1111/j.1467-2995.2012.00727.x
Shinohara A, Nozaki-Taguchi N, Yoshimura A, Hasegawa M, Saito K, Okazaki J, et al. Hypercapnia versus normocapnia for emergence from desflurane anaesthesia: Single-blinded randomised controlled study. Eur J Anaesthesiol. 2021;38(11):1148–57. doi: https://doi.org/10.1097/EJA.0000000000001574
Kadoi Y, Nishida A, Saito S. Recovery time after sugammadex reversal of rocuronium-induced muscle relaxation for electroconvulsive therapy is independent of cardiac output in both young and elderly patients. J ECT. 2013;29(1):33–6. doi: https://doi.org/10.1097/YCT.0b013e31826cf348
Yoshida F, Suzuki T, Kashiwai A, Furuya T, Konishi J, Ogawa S. Correlation between cardiac output and reversibility of rocuronium-induced moderate neuromuscular block with sugammadex. Acta Anaesthesiol Scand. 2012;56(1):83–7. doi: https://doi.org/10.1111/j.1399-6576.2011.02589.x
Downloads
Copyright (c) 2020 Sociedad Colombiana de Anestesiología y Reanimación (S.C.A.R.E.)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
| Article metrics | |
|---|---|
| Abstract views | |
| Galley vies | |
| PDF Views | |
| HTML views | |
| Other views | |
