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Anesthesia Inhalation Agents and Their Cardiovascular Effects
Introduction
Over the past several decades, multiple studies and clinical practice have demonstrated the cardiovascular effects of inhalation anesthetic agents. Early anesthetics included diethyl ether and nitrous oxide, whereas more recent halogenated agents include isoflurane, desflurane, and sevoflurane. Halogenated agents produce similar circulatory effects in young, healthy individuals during maintenance anesthesia.[1] However, comorbidities, extremes of age, concurrent medications, and additional factors can alter the expected effects. The development of the anesthetic care team approach underscores the importance of effective communication to improve outcomes.
A significant cardiovascular effect of inhalation anesthetic agents is their impact on components of cardiac output, which can lead to reductions in blood pressure. Lowering blood pressure may benefit certain patients, such as those with hypertension, but it may also pose risks for individuals with hypotension or those predisposed to hemodynamic instability. To counteract these effects, anesthesiologists may administer medications to support blood pressure or cardiac output while closely monitoring the patient throughout the procedure.
Inhalation anesthetics can alter heart rate and rhythm. These changes may result from the direct effects of the anesthetic on the heart and contributing factors such as cardiac output fluctuations. Inhalation anesthetic agents likewise influence the respiratory system by altering breathing rate and depth. These changes can affect oxygen and carbon dioxide levels in the blood, potentially impacting cardiovascular function.
The cardioprotective effects of volatile anesthetics and certain intravenous anesthetics have been well-documented in preclinical studies, but their clinical efficacy remains uncertain. Translating these insights into clinical practice presents ongoing challenges due to the complexity of underlying mechanisms and variability in patient response.
Several recent clinical trials have investigated the cardioprotective effects of anesthetics over the past 5 years. Studies have produced mixed findings regarding the clinical relevance of volatile anesthetics for cardioprotection. Guidelines have evolved, with some endorsing the use of volatile anesthetics for cardioprotection in noncardiac surgeries or coronary artery bypass graft surgery, whereas others do not support their use.
Clinical trials have evaluated multiple anesthetic techniques, including volatile, intravenous, and xenon gas anesthetics. Some studies have found no differences in clinical outcomes between volatile and intravenous anesthetics, whereas others have reported biomarker improvements that did not translate into clinical benefits. Meta-analyses have consistently shown reductions in morbidity or mortality with volatile anesthetics compared to total intravenous anesthesia. Xenon gas has also been explored as a cardioprotective agent, but its clinical advantages over other anesthetics remain uncertain.[2]
Function
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Function
Halogenated agents, including sevoflurane, desflurane, isoflurane, enflurane, and halothane, decrease mean arterial pressure in a dose-dependent manner as concentrations of the anesthetic gas increase.[3][4][3] The mean arterial pressure is reduced primarily due to decreased systemic vascular resistance, except for halothane, which lowers mean arterial pressure by directly affecting the myocardium and reducing cardiac output without altering systemic vascular resistance.[5] Sevoflurane has shown a lesser effect on hemodynamic and cardiovascular parameters compared to desflurane and isoflurane, contributing to lower morbidity and mortality.[6] Unlike other inhaled anesthetics, nitrous oxide does not affect mean arterial pressure. When combined with halogenated agents, nitrous oxide mitigates or even reverses mean arterial pressure reductions.[7][8][9][10]
Cardiac output decreases as inhaled anesthetic concentrations rise. In healthy individuals, an increase in heart rate partially compensates for this reduction, preserving cardiac output at clinically relevant concentrations. However, comorbidities, advanced age, and concurrent medications may impair this compensatory response, leading to a decline in cardiac output.[11]
Tachycardia commonly occurs during the maintenance phase of halogenated inhalation anesthesia and is considered a compensatory response to reduced cardiac output. Heart rate increases in a dose-dependent manner, with variations among agents. The concentration of inhalation anesthetics is standardized by the minimum alveolar concentration (MAC), which represents the concentration at which 50% of patients do not physically respond to a painful stimulus. Tachycardia typically occurs at the following concentrations—0.25 MAC for isoflurane, 1.0 MAC for desflurane, and 1.5 MAC for sevoflurane.[12]
The effects of these agents on sympathetic and parasympathetic activity may contribute to variations in their actions. For example, isoflurane increases sympathetic activity alone, whereas sevoflurane enhances both sympathetic and parasympathetic activity when combined with nitrous oxide.[13]
Rapid increases in desflurane and isoflurane concentrations produce distinct effects on heart rate compared to maintenance levels. Desflurane elicits the most pronounced response. A rapid increase in desflurane concentration from 4% to 8% within 1 minute may cause heart rate and blood pressure to double above baseline in the absence of opioids, β-blockers, or clonidine.[14] This response is driven by a significant rise in sympathetic and renin-angiotensin-aldosterone system activity. However, the effect diminishes after 30 minutes, suggesting receptor adaptation. Sevoflurane does not demonstrate this response during rapid concentration increases. A recent study found that heart rate remained stable despite epileptiform and generalized periodic discharges observed on electroencephalography.[15]
Issues of Concern
Sevoflurane, desflurane, and isoflurane prolong the QT interval on electrocardiography in healthy adults without concurrent medication.[16] The administration of inhaled anesthetics in patients with congenital or acquired long QT syndrome raises concerns about the potential for malignant arrhythmias.[17] Case reports have documented torsade de pointes ("twisting of the points") in patients with congenital long QT syndrome following the use of inhaled anesthetics.[18][19] However, when administered alongside preoperative β-blockers, all modern inhaled anesthetics have been used safely in patients with long QT syndrome. Notably, a recent study of pediatric patients aged 2 to 12 undergoing general anesthesia with sevoflurane or desflurane found no effect on the QT interval, regardless of the anesthetic used.[20][21]
Debate continues over the use of inhaled versus intravenous anesthetic agents during coronary artery bypass graft surgery in patients with coronary artery disease. Studies comparing overall morbidity and mortality outcomes have yielded conflicting results. Recent large meta-analyses suggest that sevoflurane may provide a more favorable cardioprotective effect during cardiac surgery compared to propofol. However, these analyses have not demonstrated differences in morbidity and mortality.[22]
There is no evidence to support the claim that isoflurane can induce coronary steal syndrome. Instead, halogenated agents have shown ischemic preconditioning effects on the myocardium in cases of compromised regional perfusion. This cardioprotective effect occurs in 2 phases—an initial window lasting 1 to 2 hours after the conditioning episode, followed by a second window that emerges 24 hours later and may persist for up to 3 days.
The underlying mechanism in cardiomyocytes has been linked to the selective priming of mitochondrial adenosine triphosphate-sensitive potassium channels through multiple protein kinase C–coupled signaling pathways.[23][24] Despite growing evidence, further studies are necessary to determine the clinical significance of perioperative cardiac protection with inhaled anesthetics.[25]
Clinical Significance
Inhaled anesthetics are widely used for general anesthesia. Anesthesia providers must understand the cardiovascular effects and nuanced differences among these agents. Hemodynamic instability is associated with an increased risk of myocardial infarction. Therefore, the risks and benefits of general anesthesia should be assessed on a case-by-case basis.[26] Among currently used inhaled anesthetics, sevoflurane has demonstrated the lowest morbidity and mortality and the least pronounced cardiovascular effects.
Perioperative complications remain a significant concern. Major adverse cardiac events affect up to 18% of cardiac surgeries and 2.6% of noncardiac surgeries. The selection of inhaled anesthetics, intravenous anesthetics, or a combination of both depends on patient- and surgery-specific factors. No universally accepted approach exists, and debate continues regarding the optimal anesthetic technique. Resolving these questions requires years, if not decades, of research. Until then, each anesthetic agent should be considered individually, with a thorough risk-benefit analysis tailored to the patient and surgical procedure.
Inhalational anesthetic agents are widely used in clinical practice for surgical anesthesia. However, the cardiovascular effects of these agents require careful consideration during administration.
Over the past several decades, extensive research has investigated the impact of inhalational anesthetics on cardiac output, heart rate, systemic vascular resistance, cardiac conduction, myocardial contractility, coronary blood flow, and blood pressure. These effects are dose-dependent and vary by agent. Halogenated agents, including isoflurane, desflurane, and sevoflurane, produce similar circulatory effects in young, healthy individuals during maintenance anesthesia. However, comorbidities, age extremes, concurrent medications, and other factors can alter these expected effects.[27]
Inhaled anesthetics decrease mean arterial pressure in a dose-dependent manner, primarily by reducing systemic vascular resistance. These agents also reduce ventilation and blunt responses to hypercapnia and hypoxia. Cerebral blood flow and intracranial pressure increase while cerebral metabolic rate decreases. Inhaled anesthetics exert a protective effect on myocardial tissue during ischemic injury but may also trigger malignant hyperthermia in susceptible patients. Additional effects include increased intraocular pressure and depressed mucociliary function in the airway. In older patients with cardiovascular disease, inhaled anesthetics can further reduce cardiac index by depressing contractility and slowing heart rate.
Other Issues
Hemodynamic instability poses a significant challenge when administering inhaled anesthetics to older adults. Age-related changes, including vascular and myocardial stiffening and heightened sympathetic activity, increase susceptibility to hemodynamic fluctuations. In addition, older patients often present with multiple comorbidities and polypharmacy, further complicating cardiovascular regulation. In young, healthy adults, compensatory tachycardia helps preserve cardiac output. However, this response diminishes with aging. Inhaled anesthetics may further reduce the cardiac index in older patients by depressing contractility and slowing heart rate, leading to a more pronounced reduction in cardiac output compared to younger individuals.[28][29]
Pulmonary hypertension carries a high risk of mortality in patients requiring invasive mechanical ventilation.[30][31] Inhaled nitrous oxide induces pulmonary vasoconstriction, which can significantly exacerbate preexisting pulmonary hypertension.[32][33] As a result, nitrous oxide is contraindicated in these patients. Conversely, inhaled nitric oxide selectively induces pulmonary vasodilation, improving oxygenation and reducing intrapulmonary shunting.[34][35] The Food and Drug Administration has approved this treatment for pulmonary hypertension in both pediatric and adult patients. When used alongside other inhaled anesthetics, nitric oxide may enhance the safety of general anesthesia in patients with pulmonary hypertension.
Enhancing Healthcare Team Outcomes
The evolution of anesthetic care teams underscores the importance of open communication among interprofessional healthcare team members throughout the preoperative, intraoperative, and postoperative periods. Collaborative selection of the anesthetic modality before surgery on a case-by-case basis contributes to better patient outcomes. Maintaining flexibility during the intraoperative period requires clear and continuous communication within the anesthetic care team to adapt to changing conditions. Postoperative case reviews further enhance future outcomes by facilitating continuous improvement. Effective communication among anesthesiologists, nurse anesthetists, surgeons, and recovery room nurses fosters a cohesive approach, optimizing patient safety and reducing the risk of adverse cardiac events associated with anesthetic agents.
Skills
Understanding the cardiovascular effects of inhaled anesthetic agents is critical in the perioperative setting. Effective perioperative management requires collaboration among interprofessional team members. The choice of inhaled anesthetic agents and the selection of a specific agent should consider patient-specific factors, surgical considerations, and perioperative circumstances.
Strategy
Maintaining continuous, closed-loop communication within the perioperative care team ensures appropriate decision-making regarding the use of inhaled anesthetic agents. Clear communication about the selected technique and potential management concerns enhances patient safety and facilitates coordinated care.
Ethics
Before inducing anesthesia, comprehensive informed consent must be obtained from either the patient or, when the patient lacks capacity, an authorized decision-maker. All team members should feel empowered to express any concerns to the team or the patient, ensuring stakeholder buy-in while providing additional layers of review and early identification of potential issues.
Responsibilities
All team members must communicate responsibilities, concerns, and actions with colleagues throughout the perioperative period. Timely and transparent communication ensures coordinated and efficient patient care.
Interprofessional Communication
A respectful exchange of information and concerns among team members is essential. The perioperative environment should promote open dialogue without fostering hostility or intimidation.
Care Coordination
Team members should prioritize collaboration by avoiding disruptions to colleagues' workflow. Actions and decisions should minimize additional burdens on the team, ensuring efficient and effective patient care.
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