Anesthesia Inhalation Agents Cardiovascular Effects

Article Author:
Samuel Eis
Article Editor:
Jeremy Kramer
Updated:
5/17/2019 12:32:57 PM
PubMed Link:
Anesthesia Inhalation Agents Cardiovascular Effects

Introduction

Multiple studies and clinical practice throughout the past several decades have demonstrated the cardiovascular effects of inhalation anesthetic agents. These anesthetics include the early agents of diethyl ether and nitrous oxide to the latest halogenated agents such as isoflurane, desflurane, and sevoflurane. The halogenated agents all have similar circulatory effects as seen in young healthy volunteers during maintenance anesthesia.[1] However, comorbidities, extremes in age, concurrent medication, and other associated factors compound the predicted effects. With the development of the anesthetic care team approach, it is important to maintain effective communication to improve overall outcomes.

Function

Halogenated agents including sevoflurane, desflurane, isoflurane, enflurane, and halothane all decrease mean arterial pressure (MAP) with increasing concentrations of the anesthetic gas in a dose-dependent manner.[2][3][4] The mechanism of the decrease in MAP is related to a decrease in systemic vascular resistance (SVR) with the exception of halothane which decreases the MAP by directly affecting the myocardium and thereby decreasing cardiac output (CO) without changes in SVR.[3][4] Sevoflurane has demonstrated to have less of an impact on hemodynamic and cardiovascular parameters than desflurane and isoflurane, leading to reduced morbidity and mortality.[2][5] Nitrous oxide, different from other inhaled anesthetics, does not affect mean arterial pressure. Thus, when nitrous oxide is combined with halogenated agents, the reduction in MAP is minimized or even reversed.[6][7]

Cardiac output (CO) is reduced with increasing concentrations of inhaled anesthetics.[2][1] In healthy individuals, this reduction in CO is partially compensated by an increase in heart rate. Therefore, at clinically relevant concentrations and in healthy adults, the cardiac output is usually preserved. Comorbidities, older age, and concurrent medication may inhibit this compensatory mechanism and thereby result in an overall reduction of CO.[8]

Tachycardia is commonly seen during maintenance administration of halogenated inhalation agents and is thought to be compensatory to the reduction in cardiac output as described above. The heart rate is dose-dependent as concentration increases and is slightly different for each agent. The concentration of inhalation anesthetics is standardized by the minimum alveolar concentration (MAC), a known concentration of inhaled anesthetic at which fifty percent of patients do not elicit a physical response to a painful stimulus. Tachycardia is typically induced at the following concentrations for isoflurane, desflurane, and sevoflurane respectively: 0.25, 1.0, and 1.5 MAC.[9] The different response between agents may be related to the balance between sympathetic and parasympathetic activity. Isoflurane is seen to only increase sympathetic activity whereas sevoflurane increases both sympathetic and parasympathetic activity as seen when combined with nitrous oxide.[10]

Rapid increases in the concentration of desflurane and isoflurane have significant effects on the heart rate, different from maintenance dose as described above. Desflurane has the most profound response. An abrupt increase of desflurane concentration from 4% to 8% in less than a minute may result in a doubling of the heart rate and blood pressure above baseline in the absence of opiates, beta blockers, or clonidine.[11] The mechanism is related to a large increase in sympathetic and renin-angiotensin activity. However, this response is not seen after repetitive increases in concentration after 30 minutes, suggesting the receptors involved in the response are adaptive. Sevoflurane does not exhibit this property when the concentration is rapidly increased. A recent study demonstrated the heart rate remained unaffected during rapid increases in sevoflurane concentration despite epileptiform and generalized periodic discharges noted on EEG.[12]

Issues of Concern

Sevoflurane, desflurane, and isoflurane, all prolong the QT interval on the electrocardiogram in healthy adults without concurrent medication.[13] When administering inhaled anesthetics to patients with known congenital or acquired long QT interval syndrome (LQTS), there is some concern for developing malignant arrhythmias.[14] There have been multiple case reports of patients with congenital LQTS who have developed torsade de pointes after administration of inhaled anesthetics.[15][16] However, when used in conjunction with preoperative beta-blocking agents, patients with known LQTS have been safely anesthetized using all modern inhaled anesthetics.[14][17] Of note, a recent study of pediatric patients ages 2 to 12 undergoing general anesthesia with sevoflurane or desflurane demonstrated no effect on the QT interval regardless of which anesthetic agent was in use.[18]

In patients with coronary artery disease, there is debate regarding the use of inhaled anesthetic agents versus intravenous anesthetic agents during coronary artery bypass surgery.[2] Numerous studies have conflicting results when comparing overall morbidity and mortality outcomes. More recently, multiple large meta-analyses have demonstrated that sevoflurane may exhibit a more favorable cardioprotective effect during cardiac surgery than propofol, although they failed to demonstrate differences in morbidity and mortality.[5][19] While there were concerns that isoflurane may induce coronary steal syndrome, halogenated agents have instead demonstrated ischemic preconditioning effects on myocardium in the setting of compromised regional perfusion. Two windows of protection have been demonstrated; the first window appears for the first one to two hours after the conditioning episode and then dissipates. The second window appears twenty-four hours after the conditioning episode and may last as long as three days.[5] The mechanism of protection in cardiomyocytes has been linked to selective priming of mitochondrial adenosine triphosphate-sensitive potassium channels (mK-ATP channels) through multiple triggering protein kinase C-coupled signaling pathways.[20][21] Despite the current amount of evidence, further studies are recommended to assess the clinical significance of perioperative cardiac protection using inhaled anesthetics.[22]

Clinical Significance

Inhaled anesthetics enjoy extensive use for general anesthesia. As a result, it is essential that the anesthesia provider is aware of the cardiovascular effects and intricate differences among the various agents. Because hemodynamic instability correlates with increased risk of myocardial infarction, the risks, and benefits of undergoing general anesthesia merit consideration on a case by case basis.[2][23] Sevoflurane has been demonstrated to have the least morbidity and mortality of the currently used inhaled anesthetics and has the least pronounced cardiovascular effects.

Other Issues

Hemodynamic instability is one of the major challenges associated with inhaled anesthetics and the elderly.[8] Changes associated with aging such as vascular stiffening, myocardial stiffening, and sympathetic overactivity all result in making the elderly more prone to hemodynamic instability. Additionally, the elderly often have numerous comorbidities and associated polypharmacy that affect the hemodynamic system. In young, healthy adults, the cardiac output is frequently preserved by compensatory tachycardia as described above; however, this compensatory response diminishes in the elderly. Also, inhaled anesthetics may further reduce cardiac index in the elderly by depressing contractility and slowing heart rate. Therefore, there is a more pronounced reduction in cardiac output in the elderly during the administration of inhaled anesthetics when compared to younger patients.[8][24][25]

Pulmonary hypertension is associated with a high risk of mortality in patients who undergo invasive mechanical ventilation.[26][27] Inhaled nitrous oxide induces pulmonary vasculature constriction and may significantly worsen pre-existing pulmonary hypertension.[28][29] Therefore, it is contraindicated to administer nitrous oxide in patients with pulmonary hypertension. On the other hand, inhaled nitric oxide has the unique ability to induce vasodilation in the pulmonary vasculature, promoting improved oxygenation of blood and reduced intrapulmonary shunting.[30][31] It is currently FDA approved to treat pulmonary hypertension in children and adults. Nitric oxide may be used in conjunction with other inhaled anesthetics to improve the safety of general anesthesia in patients with pulmonary hypertension.

Enhancing Healthcare Team Outcomes

With the evolution of anesthetic care teams, it is vital to maintain open communication in the pre-operative, intra-operative, and post-operative periods between members of the interdisciplinary team.  Choosing the anesthetic modality as a team pre-operatively on a case by case basis is essential to the overall outcome of each case. Maintaining flexibility to allow for changes in the intraoperative period requires optimal communication within the anesthetic care team. Reanalyzing the case as a team in the post-operative period allows for improved outcomes in future cases. Overall, communication is essential to improving outcomes within anesthetic care teams that include the nurse anesthetist, surgeon, recovery room nurses, and the anesthesiologist. [Level V]


References

[1] Cahalan MK,Weiskopf RB,Eger EI 2nd,Yasuda N,Ionescu P,Rampil IJ,Lockhart SH,Freire B,Peterson NA, Hemodynamic effects of desflurane/nitrous oxide anesthesia in volunteers. Anesthesia and analgesia. 1991 Aug;     [PubMed PMID: 1854030]
[2] Brioni JD,Varughese S,Ahmed R,Bein B, A clinical review of inhalation anesthesia with sevoflurane: from early research to emerging topics. Journal of anesthesia. 2017 Oct;     [PubMed PMID: 28585095]
[3] Torri G, Inhalation anesthetics: a review. Minerva anestesiologica. 2010 Mar;     [PubMed PMID: 20203550]
[4] Tanaka S,Tsuchida H,Nakabayashi K,Seki S,Namiki A, The effects of sevoflurane, isoflurane, halothane, and enflurane on hemodynamic responses during an inhaled induction of anesthesia via a mask in humans. Anesthesia and analgesia. 1996 Apr;     [PubMed PMID: 8615504]
[5] Li F,Yuan Y, Meta-analysis of the cardioprotective effect of sevoflurane versus propofol during cardiac surgery. BMC anesthesiology. 2015 Sep 24;     [PubMed PMID: 26404434]
[6] Becker DE,Rosenberg M, Nitrous oxide and the inhalation anesthetics. Anesthesia progress. 2008 Winter;     [PubMed PMID: 19108597]
[7] Weiskopf RB,Cahalan MK,Ionescu P,Eger EI 2nd,Yasuda N,Lockhart SH,Rampil IJ,Laster M,Freire B,Peterson N, Cardiovascular actions of desflurane with and without nitrous oxide during spontaneous ventilation in humans. Anesthesia and analgesia. 1991 Aug;     [PubMed PMID: 1854031]
[8] Das S,Forrest K,Howell S, General anaesthesia in elderly patients with cardiovascular disorders: choice of anaesthetic agent. Drugs     [PubMed PMID: 20359259]
[9] De Deyne C,Joly LM,Ravussin P, [Newer inhalation anaesthetics and neuro-anaesthesia: what is the place for sevoflurane or desflurane?]. Annales francaises d'anesthesie et de reanimation. 2004 Apr;     [PubMed PMID: 15120783]
[10] Nishiyama T, Changes in heart rate variability during anaesthesia induction using sevoflurane or isoflurane with nitrous oxide. Anaesthesiology intensive therapy. 2016;     [PubMed PMID: 27689429]
[11] Weiskopf RB,Moore MA,Eger EI 2nd,Noorani M,McKay L,Chortkoff B,Hart PS,Damask M, Rapid increase in desflurane concentration is associated with greater transient cardiovascular stimulation than with rapid increase in isoflurane concentration in humans. Anesthesiology. 1994 May;     [PubMed PMID: 8017643]
[12] Sonkaj�rvi E,Rytky S,Alahuhta S,Suominen K,Kumpulainen T,Ohtonen P,Karvonen E,J�ntti V, Epileptiform and periodic EEG activities induced by rapid sevoflurane anaesthesia induction. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology. 2018 Mar;     [PubMed PMID: 29414407]
[13] Yildirim H,Adanir T,Atay A,Katircio?lu K,Savaci S, The effects of sevoflurane, isoflurane and desflurane on QT interval of the ECG. European journal of anaesthesiology. 2004 Jul;     [PubMed PMID: 15318470]
[14] Booker PD,Whyte SD,Ladusans EJ, Long QT syndrome and anaesthesia. British journal of anaesthesia. 2003 Mar;     [PubMed PMID: 12594150]
[15] Kumakura M,Hara K,Sata T, Sevoflurane-associated torsade de pointes in a patient with congenital long QT syndrome genotype 2. Journal of clinical anesthesia. 2016 Sep;     [PubMed PMID: 27555138]
[16] Choromanski DW,Amin S,Zestos MM, SEVOFLURANE AS A CAUSE OF TORSADE DE POINTES IN PATIENT WITH THE LONG QT SYNDROME: Case Report. Middle East journal of anaesthesiology. 2016 Feb;     [PubMed PMID: 27382818]
[17] Delgado-Herrera L,Ostroff RD,Rogers SA, Sevoflurance: approaching the ideal inhalational anesthetic. a pharmacologic, pharmacoeconomic, and clinical review. CNS drug reviews. 2001 Spring;     [PubMed PMID: 11420572]
[18] Lee JH,Kim EH,Jang YE,Kim JT,Kim HS, Inhalation of Sevoflurane and Desflurane Can Not Affect QT Interval, Corrected QT, Tp-Te/QT or Tp-Te/JT in Children. Chinese medical journal. 2018 Mar 20;     [PubMed PMID: 29521299]
[19] Landoni G,Guarracino F,Cariello C,Franco A,Baldassarri R,Borghi G,Covello RD,Gerli C,Crivellari M,Zangrillo A, Volatile compared with total intravenous anaesthesia in patients undergoing high-risk cardiac surgery: a randomized multicentre study. British journal of anaesthesia. 2014 Dec;     [PubMed PMID: 25186820]
[20] Zaugg M,Lucchinetti E,Spahn DR,Pasch T,Schaub MC, Volatile anesthetics mimic cardiac preconditioning by priming the activation of mitochondrial K(ATP) channels via multiple signaling pathways. Anesthesiology. 2002 Jul;     [PubMed PMID: 12131097]
[21] Landoni G,Biondi-Zoccai GG,Zangrillo A,Bignami E,D'Avolio S,Marchetti C,Calabr� MG,Fochi O,Guarracino F,Tritapepe L,De Hert S,Torri G, Desflurane and sevoflurane in cardiac surgery: a meta-analysis of randomized clinical trials. Journal of cardiothoracic and vascular anesthesia. 2007 Aug;     [PubMed PMID: 17678775]
[22] Chen S,Lotz C,Roewer N,Broscheit JA, Comparison of volatile anesthetic-induced preconditioning in cardiac and cerebral system: molecular mechanisms and clinical aspects. European journal of medical research. 2018 Feb 20;     [PubMed PMID: 29458412]
[23] Walsh M,Devereaux PJ,Garg AX,Kurz A,Turan A,Rodseth RN,Cywinski J,Thabane L,Sessler DI, Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013 Sep;     [PubMed PMID: 23835589]
[24] McKinney MS,Fee JP,Clarke RS, Cardiovascular effects of isoflurane and halothane in young and elderly adult patients. British journal of anaesthesia. 1993 Nov;     [PubMed PMID: 8251283]
[25] Malan TP Jr,DiNardo JA,Isner RJ,Frink EJ Jr,Goldberg M,Fenster PE,Brown EA,Depa R,Hammond LC,Mata H, Cardiovascular effects of sevoflurane compared with those of isoflurane in volunteers. Anesthesiology. 1995 Nov;     [PubMed PMID: 7486177]
[26] Rush B,Biagioni BJ,Berger L,McDermid R, Mechanical Ventilation Outcomes in Patients With Pulmonary Hypertension in the United States: A National Retrospective Cohort Analysis. Journal of intensive care medicine. 2017 Dec;     [PubMed PMID: 27279084]
[27] Wang L,Luo H,Qin G,Cao Y,Gao X,Zhang Z,Ye Z,Zhang J,Guo Q,Wang E, The Impact of Sevoflurane on Coupling of the Left Ventricular-to-Systemic Vasculature in Rats With Chronic Pulmonary Hypertension. Journal of cardiothoracic and vascular anesthesia. 2017 Dec;     [PubMed PMID: 28533073]
[28] Myles PS,Leslie K,Peyton P,Paech M,Forbes A,Chan MT,Sessler D,Devereaux PJ,Silbert BS,Jamrozik K,Beattie S,Badner N,Tomlinson J,Wallace S, Nitrous oxide and perioperative cardiac morbidity (ENIGMA-II) Trial: rationale and design. American heart journal. 2009 Mar;     [PubMed PMID: 19249419]
[29] Myles PS,Leslie K,Silbert B,Paech MJ,Peyton P, A review of the risks and benefits of nitrous oxide in current anaesthetic practice. Anaesthesia and intensive care. 2004 Apr;     [PubMed PMID: 15957712]
[30] Yu B,Ichinose F,Bloch DB,Zapol WM, Inhaled nitric oxide. British journal of pharmacology. 2019 Jan;     [PubMed PMID: 30288739]
[31] Sim JY, Nitric oxide and pulmonary hypertension. Korean journal of anesthesiology. 2010 Jan;     [PubMed PMID: 20498805]