Maximum Dose of Local Anesthesia

Local anesthetics are essential pharmacological agents used in medical, surgical, and dental procedures to provide temporary loss of sensation while maintaining consciousness. Their administration must follow established guidelines regarding recommended doses to prevent systemic toxicity and adverse effects. The optimal dose and duration of action depend on the specific agent, route of administration, patient weight, metabolism, and whether a vasoconstrictor such as epinephrine is used to prolong efficacy. Clinicians must understand the maximum dose of local anesthesia that can be administered safely.

Bupivacaine, a long-acting agent used for local anesthesia, has a maximum recommended dose of 2.5 mg/kg without epinephrine and 3 mg/kg with epinephrine. Its prolonged duration of action, typically lasting between 3 to 9 hours, makes it ideal for procedures requiring extended pain relief. However, its cardiotoxicity at high doses remains a significant concern, as it has been associated with severe ventricular arrhythmias and cardiac arrest (1).

Lidocaine, one of the most commonly used local anesthetics, has a maximum recommended dose of 4.5 mg/kg without epinephrine and 7 mg/kg with epinephrine. It is characterized by a rapid onset of action and moderate duration, typically lasting 30 to 60 minutes when used for infiltration anesthesia, and up to 120 minutes when combined with epinephrine (2).

Mepivacaine, structurally similar to lidocaine, has a maximum recommended dose of 4.4 mg/kg without a vasoconstrictor and 6.6 mg/kg with levonordefrin. Its duration of action ranges from 45 to 90 minutes, making it a preferred choice for shorter dental and surgical procedures. Ropivacaine, a bupivacaine analog with reduced cardiotoxicity, has a maximum recommended dose of 3 mg/kg without epinephrine and 3.5 mg/kg with epinephrine. It provides prolonged analgesia with a lower risk of cardiac complications, making it ideal for epidural and peripheral nerve block procedures (3).

Procaine, one of the earliest synthetic local anesthetics, has a significantly higher maximum dose of 14 mg/kg due to its rapid hydrolysis by plasma esterases. Its short duration of action, typically 15 to 30 minutes, limits its use to minor procedures where prolonged anesthesia is unnecessary (4). Articaine, another common dental anesthetic, has a higher lipid solubility and rapid onset, allowing for effective pulpal anesthesia. Its maximum recommended dose is 7 mg/kg, and its duration of action is typically between 60 to 120 minutes when administered with epinephrine.

Toxicity from excessive doses of local anesthetic can lead to systemic complications, primarily affecting the central nervous system (CNS) and cardiovascular system. Early signs of toxicity include perioral numbness, tinnitus, dizziness, and muscle twitching. If untreated, toxicity may progress to seizures, respiratory depression, and cardiovascular collapse. The severity of these effects depends on factors such as the rate of systemic absorption, patient comorbidities, and concurrent drug interactions. Bupivacaine-induced cardiotoxicity is particularly difficult to manage due to its strong binding affinity to cardiac sodium channels. Recent advances in treatment, such as lipid emulsion therapy, have improved outcomes in cases of severe local anesthetic systemic toxicity (LAST), particularly with high-dose bupivacaine exposure (5).

Safe administration practices are critical to minimizing the risk of toxicity. Clinicians should use the lowest effective dose and administer the anesthetic gradually while monitoring for signs of intravascular injection. Aspiration prior to injection, slow administration, and proper patient positioning can reduce systemic absorption and decrease the likelihood of toxicity. In addition, advances in adjunct medications such as dexmedetomidine and clonidine have demonstrated efficacy in prolonging the duration of local anesthesia while reducing the required doses.

References

Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: a multifactorial concept. Reg Anesth Pain Med. 2004;29(6):564-524. doi:10.1016/j.rapm.2004.08.003
Moore PA, Hersh EV. Local anesthetics: pharmacology and toxicity. Dent Clin North Am. 2010;54(4):587-599. doi:10.1016/j.cden.2010.06.015
Yagiela JA. Local anesthetics. Anesth Prog. 1991;38(4-5):128-141.
Gunter JB. Benefit and risks of local anesthetics in infants and children. Paediatr Drugs. 2002;4(10):649-672. doi:10.2165/00128072-200204100-00003
Gitman M, Fettiplace MR, Weinberg GL, Neal JM, Barrington MJ. Local Anesthetic Systemic Toxicity: A Narrative Literature Review and Clinical Update on Prevention, Diagnosis, and Management. Plast Reconstr Surg. 2019;144(3):783-795. doi:10.1097/PRS.0000000000005989

Sex Differences in Response to Anesthesia

When anesthesia providers administer anesthesia to relieve pain, relax and sedate patients, prevent movement during surgery, ensure that patients have no awareness or memory of procedures, or achieve a combination of those goals, anesthesia must be adjusted to the individual patient’s responses. Many factors affect how anesthesia affects different people, including differences associated with sex.

Sex, referring to the set of frequently consistent biological variables resulting from one’s chromosomal composition,¹ will be represented in dichotomy (i.e., “woman” or “man”) in this article. It is important to note that (1) at times, chromosomal composition and the resultant phenotype do not always match in a way consistent with typical patterns, (2) sexual chromosomal compositions are not limited to XX or XY, (3) sex and gender are separate concepts, the latter of which will not be addressed in this article, and (4) many prior scientific articles have conflated sex and gender; thus, this article will use only sex-based terms, though the data from which it is produced may have proxied gender for sex or vice versa.

Sexual dimorphism among humans extends to physiological differences that can affect the metabolism of volatile and intravenous anesthetics.² Some of these differences for women often include a smaller cardiac mass—estimated to be on average 15–30% smaller in women compared to men—lower lung volumes, a greater stress glucocorticoid response, and a greater sensitivity to baroreflex stimulation.²

Women on average have a greater volume of distribution for and clearance of the highly-lipophilic anesthetizing agent, propofol; therefore, greater doses are likely to be required for women when compared to men.³ Specifically, a 2003 study suggested that men might require a 30–40% reduction in the dose of propofol when compared to women.³

Additionally, for those who experience menstruation, progesterone, the predominant hormone during the luteal phase, can accentuate the effects of propofol through increases in cortical agonism of the gamma-aminobutyric acid type A (i.e., GABA-A) receptor functioning.^4,5 As such, one study demonstrated that propofol requirements for loss of eyelash reflex—an estimate of loss of consciousness—and time for bispectral index—a proprietary tool used for measuring the degree of consciousness—to reach 50 were found to be statistically significantly the least and shortest, respectively, for participants currently in the luteal phase. In other words, study participants in the luteal phase were more sensitive to propofol than participants in other menstrual phases.

Similar non-human animal studies have supported the existence of sex-mediated physiological differences in the metabolism of and response to volatile anesthesia. In a 2024 study using mice, researchers demonstrated that female mice regained consciousness and sentience more quickly following anesthetic exposure, demonstrated through observation of neuronal activity within sleep-promoting regions of the ventral hypothalamus. Thus, it was discovered that female mice regain consciousness at a faster rate than their counterparts.⁶ This sexual dimorphism is hypothesized to be mediated by differential concentrations of testosterone, which produces increased sensitivity to anesthesia.⁶ The role of testosterone in increasing sensitivity to volatile anesthetics was further supported when the administration of letrozole, an aromatase inhibitor which prevents the conversion of testosterone to estrogens, diminished anesthetic sensitivity.⁶

Data suggest that physiological sex differences in humans extend to differing responses to volatile and intravenous anesthesia. On average, women tend to be more resistant to the sedating effects of anesthetics, largely mediated by a larger volume of distribution for lipophilic anesthetics, as well as by the estrogenic protective effects on the regions of the hypothalamus responsible for consciousness and awakening.

References

1. Johnson JL, Repta R. Sex and Gender: Beyond the Binaries. In: Designing and Conducting Gender, Sex, & Health Research. SAGE Publications, Inc.; 2012:17-38. doi:10.4135/9781452230610.n2

2. Filipescu D, Ştefan M. Sex and gender differences in anesthesia: Relevant also for perioperative safety? Best Pract Res Clin Anaesthesiol. 2021;35(1):141-153. doi:10.1016/j.bpa.2020.12.006

3. Pleym H, Spigset O, Kharasch ED, Dale O. Gender differences in drug effects: implications for anesthesiologists. Acta Anaesthesiol Scand. 2003;47(3):241-259. doi:10.1034/j.1399-6576.2003.00036.x

4. Bitran D, Purdy RH, Kellog CK. Anxiolytic effect of progesterone is associated with increases in cortical alloprenanolone and GABAA receptor function. Pharmacol Biochem Behav. 1993;45(2):423-428. doi:10.1016/0091-3057(93)90260-Z

5. Liu YW, Zuo W, Ye JH. Propofol stimulates noradrenalin-inhibited neurons in the ventrolateral preoptic nucleus by reducing GABAergic inhibition. Anesth Analg. 2013;117(2):358-363. doi:10.1213/ANE.0b013e318297366e

6. Wasilczuk AZ, Rinehart C, Aggarwal A, et al. Hormonal basis of sex differences in anesthetic sensitivity. Proc Natl Acad Sci. 2024;121(3):e2312913120. doi:10.1073/pnas.2312913120

Fiberoptic Intubation: Steps and Usage

Fiberoptic intubation (FOI) is a valuable technique for managing difficult airways in both anticipated and unanticipated scenarios. This method allows for direct visualization of the airway anatomy and precise placement of the endotracheal tube, making it particularly useful in patients with challenging airway characteristics. FOI can be performed on awake or anesthetized patients, with the awake technique being preferred for those with anticipated difficult airways. This article reviews the uses of fiberoptic intubation and the steps involved with the procedure.

The procedure begins with thorough patient preparation. Equipment, including the flexible fiberoptic bronchoscope, endotracheal tube, lubricant, and suction, is assembled. The patient is positioned either supine or seated, and standard airway and emergency equipment are made available. An antisialagogue, such as glycopyrrolate, may be administered if not contraindicated in order to reduce saliva flow. Supplemental oxygen is provided to ensure adequate oxygenation throughout the procedure.

Topical anesthesia is a crucial piece of the steps in fiberoptic intubation, especially for awake patients. This typically involves nebulizing lidocaine to anesthetize the oropharynx, applying lidocaine gel to the nasal passages if using a nasal approach, and spraying lidocaine to the posterior pharynx and larynx. Thorough topical anesthesia enhances patient comfort and cooperation during the procedure.

The actual intubation process involves several steps when using fiberoptic equipment. First, the bronchoscope is inserted through the nose or mouth. It is then carefully advanced while identifying anatomical landmarks. The vocal cords and tracheal rings are visualized, and additional local anesthetic may be sprayed through the scope as needed. The scope is passed through the vocal cords into the trachea, followed by advancing the endotracheal tube over the bronchoscope. Tube position is confirmed visually and with end-tidal CO2 monitoring. Finally, the bronchoscope is removed while holding the tube in place, and the tube is secured and connected to the ventilator.

FOI has various clinical applications. It is particularly useful in patients with limited mouth opening, cervical spine instability, airway tumors or masses, obesity with sleep apnea, and facial trauma or burns. The technique can be performed nasally or orally, with the nasal approach being advantageous in cases of large tongue, limited mouth opening, or when an unobstructed surgical field is beneficial.

While FOI is generally safe, it is not without potential complications. These may include difficulty navigating through secretions or blood, patient anxiety or intolerance of the procedure (in awake cases), equipment malfunction, and nasal bleeding when using the nasal approach. More serious complications, though rare, can include laryngospasm, bronchospasm, and oversedation leading to respiratory depression or airway obstruction. There is also a risk of trauma to airway structures and aspiration, particularly if laryngeal reflexes are compromised. Fiberoptic intubation is a highly useful tool for airway management but requires multiple steps, meaning that other techniques, such as direct laryngoscopy, may be preferred in straightforward cases.

The success of FOI relies on thorough preparation, appropriate patient selection, and skilled execution. As with any advanced airway technique, regular practice and ongoing education are crucial for maintaining proficiency. When the steps are performed correctly, fiberoptic intubation provides a safe and effective method for securing the airway in a wide range of clinical scenarios.

References

1. Collins SR, Blank RS. Fiberoptic intubation: an overview and update. Respir Care. 2014 Jun;59(6):865-78; discussion 878-80. doi: 10.4187/respcare.03012. PMID: 24891196.

2. Calder I. Murphy P. A fibre-optic endoscope used for nasal intubation. Anaesthesia 1967; 22: 489-91. Anaesthesia. 2010 Nov;65(11):1133-6. doi: 10.1111/j.1365-2044.2010.06535.x. PMID: 20946391.

3. Practice guidelines for management of the difficult airway. A report by the American Society of Anesthesiologists Task Force on Management of the Difficult Airway. Anesthesiology. 1993 Mar;78(3):597-602. PMID: 8457062.

4. Geffin B. Anesthesia and the “problem upper airway”. Int Anesthesiol Clin. 1990;28(2):106-114. PMID: 10604785.

5. Rosenberg PH, Heinonen J, Takasaki M. Lidocaine concentration in blood after topical anaesthesia of the upper respiratory tract. Acta Anaesthesiol Scand. 1980 Apr;24(2):125-8. doi: 10.1111/j.1399-6576.1980.tb01519.x. PMID: 7386144.

Medical Specialties That Work With Anesthesiology

Anesthesiology is a critical branch of medicine focused on the relief of pain and the administration of anesthetics for surgeries, diagnostics, and therapeutic procedures. Many medical specialties rely on anesthesiology to ensure patient safety and optimal outcomes across diverse medical scenarios.

Surgery has a very close relationship with anesthesiology. Anesthesiologists manage the patient’s level of consciousness, pain, and vital functions during surgery, allowing surgeons to focus on the procedure itself. The anesthesiologist monitors the patient’s blood pressure, heart rate, oxygen levels, and other critical indicators. They also tailor anesthesia plans to meet the specific requirements of each surgery type, ensuring that the patient remains stable and comfortable from start to finish 1–3. Many different surgical specialties depend on anesthesiology.

In obstetrics, anesthesiologists play a significant role, particularly in pain management for labor and delivery. They frequently administer epidurals, a type of regional anesthesia that provides effective pain relief while allowing the mother to remain awake and responsive. Anesthesiologists are also essential in managing high-risk pregnancies or emergency situations that may require cesarean sections. In these cases, they ensure that the mother remains safe and pain-free during the procedure, while coordinating with obstetricians to facilitate a smooth delivery 4–6.

Cardiologists and anesthesiologists work together on a variety of non-surgical heart procedures. Anesthesiologists prepare patients for procedures like transesophageal echocardiograms or cardiac ablation by administering sedation or anesthesia and monitoring the heart’s response throughout the intervention 7,8.

Anesthesiologists frequently collaborate with gastroenterologists for diagnostic and therapeutic procedures, such as endoscopies, colonoscopies, and esophageal dilation. These procedures often require sedation to ensure patient comfort and cooperation, particularly in cases of anxiety or where movement needs to be minimized. Anesthesiologists assess each patient’s medical history and adjust the sedation plan based on individual needs, helping gastroenterologists perform these procedures effectively and safely 9,10.

The two specialties of anesthesiology and critical care are strongly related. Anesthesiologists are vital in intensive care units (ICUs), where they assist in managing patients with life-threatening conditions. Many anesthesiologists receive additional training in critical care, making them adept at handling ventilators, monitoring critical parameters, and providing sedation or pain relief to patients who require prolonged care. They work alongside pulmonologists, intensivists, and other ICU specialists, ensuring patients in critical condition receive the most effective and individualized care 11,12.

Anesthesiology is an interdisciplinary field that touches and collaborates with many different medical specialties. The skill set of anesthesiologists, which includes airway management, anesthesia and sedation, pain management, and rapid rescue interventions, is highly beneficial to many clinical situations.

References

1. Goyal, R. Surgeons and anesthesiologists: Need to communicate? J. Anaesthesiol.

Clin. Pharmacol. 29, 297 (2013). doi: 10.4103/0970-9185.117040

2. Cooper, J. B. Critical Role of the Surgeon–Anesthesiologist Relationship for Patient Safety. Anesthesiology 129, 402–405 (2018). doi: 10.1097/ALN.0000000000002324.

3. Anesthesiologist-Surgeon Relationships | Journal of Ethics | American Medical Association. https://journalofethics.ama-assn.org/issue/anesthesiologist-surgeon-relationships.

4. Toledano, R. D., Kodali, B.-S. & Camann, W. R. Anesthesia Drugs in the Obstetric and Gynecologic Practice. Rev. Obstet. Gynecol. 2, 93 (2009).

5. Apfelbaum, J. L. et al. Practice Guidelines for Obstetric AnesthesiaAn Updated Report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia and the Society for Obstetric Anesthesia and Perinatology. Anesthesiology 124, 270–300 (2016). doi: 10.1097/ALN.0000000000000935

6. Obstetric and Gynecologic Anesthesia | ScienceDirect. https://www.sciencedirect.com/book/9780323024204/obstetric-and-gynecologic-anesthesia.

7. Hayman, M., Forrest, P. & Kam, P. Anesthesia for interventional cardiology. J. Cardiothorac. Vasc. Anesth. 26, 134–147 (2012). DOI: 10.1053/j.jvca.2011.09.004

8. Society of Cardiovascular Anesthesiologists (SCA). https://scahq.org/.

9. Goudra, B. & Singh, P. M. Anesthesia for gastrointestinal endoscopy: A subspecialty in evolution? Saudi J. Anaesth. 9, 237 (2015). doi: 10.4103/1658-354X.154691

10. de Villiers, W. J. S. Anesthesiology and gastroenterology. Anesthesiol. Clin. 27, 57–70 (2009). doi: 10.1016/j.anclin.2008.10.007.

11. Bhattacharya, P. K., Nair, S. G., Kumar, N., Natarajan, P. & Chhanwal, H. Critical care as a career for anaesthesiologists. Indian J. Anaesth. 65, 48 (2021). doi: 10.4103/ija.IJA_1490_20

12. Hanson, C. W. et al. The Anesthesiologist in Critical Care MedicinePast, Present, and Future. Anesthesiology 95, 781–788 (2001). doi: 10.1097/00000542-200109000-00034.

Production Cost of Volatile Anesthetics

Volatile anesthetics play a crucial role in modern surgical procedures, offering reliable and reversible anesthesia for patients undergoing surgery. However, there are multiple factors affecting their use, ranging from clinical efficacy to safety profile to production cost. The production cost of volatile anesthetics is a complex interplay of raw material expenses, manufacturing processes, regulatory requirements, and environmental considerations. Understanding these factors is key to managing healthcare costs and ensuring the availability of safe and effective anesthetic agents.

The first major cost driver in the production of volatile anesthetics is the raw materials used in their formulation. These anesthetic agents are typically synthesized through halogenation processes, in which hydrocarbon compounds are chemically altered by the addition of halogen elements such as fluorine, chlorine, or bromine. These halogens are critical for the anesthetics’ efficacy and stability, but they are also expensive to obtain and handle safely ^1,2.

The manufacturing of volatile anesthetics is a highly specialized process, requiring advanced chemical engineering and quality control systems. State-of-the-art manufacturing facilities that produce volatile anesthetics involve sophisticated equipment for precision chemical reactions, distillation, and purification. These facilities are costly, often operating under strict sterile conditions, with numerous quality checks throughout the production cycle to ensure compliance with regulatory guidelines from agencies such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA) ³.

Volatile anesthetics have been scrutinized for their environmental impact, particularly their contribution to greenhouse gas emissions. Desflurane, for instance, has a global warming potential far higher than carbon dioxide, making its environmental footprint a concern for sustainability initiatives in healthcare. To reduce environmental impact, manufacturers are increasingly investing in more sustainable production methods and developing systems to capture and reduce the emission of volatile anesthetics during production and use, which increases production cost but with long-term benefits. Regulatory pressure to reduce emissions or transition to more environmentally friendly alternatives may lead to additional research and development expenses for companies producing volatile anesthetics ^4,5.

The production cost of volatile anesthetics is also influenced by market demand and competition. While sevoflurane, isoflurane, and desflurane are widely used, the market for volatile anesthetics is relatively small compared to other pharmaceutical products, leading to less competition. This can keep prices high, as manufacturers are fewer in number and are able to maintain control over pricing strategies. Additionally, patent protections on specific formulations of anesthetics can limit the entry of generic alternatives, keeping prices elevated. When patents expire, however, generic versions can help lower costs, although the complexity of producing these anesthetics often keeps their prices higher than other generic drugs ^6–8.

References

1. Reichle, F. M. & Conzen, P. F. Halogenated inhalational anaesthetics. Best Pract. Res. Clin. Anaesthesiol. (2003). doi:10.1053/bean.2002.0265

2. Fukazawa, K. & Lee, H. T. Volatile anesthetics and AKI: Risks, mechanisms, and a potential therapeutic window. Journal of the American Society of Nephrology (2014). doi:10.1681/ASN.2013111215

3. Guidance on good manufacturing practice and good distribution practice: Questions and answers. Available at: https://www.ema.europa.eu/en/human-regulatory-overview/research-development/compliance-research-development/good-manufacturing-practice/guidance-good-manufacturing-practice-good-distribution-practice-questions-answers.

4. Devlin-Hegedus, J. A., McGain, F., Harris, R. D. & Sherman, J. D. Action guidance for addressing pollution from inhalational anaesthetics. Anaesthesia (2022). doi:10.1111/anae.15785

5. Gaya da Costa, M., Kalmar, A. F. & Struys, M. M. R. F. Inhaled anesthetics: Environmental role, occupational risk, and clinical use. Journal of Clinical Medicine (2021). doi:10.3390/jcm10061306

6. Weinberg, L., Story, D., Nam, J. & McNicol, L. Pharmacoeconomics of volatile inhalational anaesthetic agents: An 11-year retrospective analysis. Anaesth. Intensive Care (2010). doi:10.1177/0310057×1003800507

7. Inhalation Anesthetics Market Dynamics, Industry Report 2030 | The Brainy Insights. Available at: https://www.thebrainyinsights.com/report/inhalation-anesthetics-market-13164.

8. Inhalation Anesthesia Market Size, Share Report, 2023-2030. Available at: https://www.grandviewresearch.com/industry-analysis/inhalation-anesthesia-market.

Effect of Sevoflurane on Cognitive Dysfunction

Sevoflurane is a common inhalational anesthetic that plays a critical role in modern surgical procedures due to its favorable properties, including rapid onset and minimal side effects. However, emerging evidence suggests that exposure to sevoflurane may have negative effects on cognitive function. In experimental animal models, sevoflurane has been linked to cognitive dysfunction¹, which may manifest as post-operative cognitive dysfunction (POCD) in elderly human patients and neurobehavioral abnormalities in younger subjects. This cognitive impairment, which can persist for weeks or even months post-surgery, raises significant concerns, particularly in aging populations who are already at higher risk for neurodegenerative conditions such as Alzheimer’s disease. Sevoflurane has also been shown to induce neuronal apoptosis and decrease adaptability in neonatal rats.² Understanding the mechanisms through which sevoflurane induces cognitive dysfunction enables the development of strategies to minimize its impact and improve patient outcomes in surgical settings.

The hippocampus is a critical neuronal structure well known to be involved in learning and memory.³ It is also an important target of general anesthetics. In 2016, researchers performed in vivo experiments on neonatal rats (n=88) to study the effect of sevoflurane anesthesia on hippocampal synaptic plasticity and, subsequently, learning and memory. 30 rat pups received 3% sevoflurane treatment for 1 hour, while another 28 received treatment for 6 hours. The remaining 30 pups served as the control group. Synaptic vesicle-associated proteins and dendrite spine density were assessed using Golgi staining, transmission electron microscopy (TEM), and western blotting. The researchers found neonatal exposure to sevoflurane treatment for 6 hours resulted in reduced spine density of apical dendrites and elevated expression of synaptic vesicle-associated proteins (SNAP-25 and syntaxin). Rats exposed to sevoflurane for 6 hours also performed worse than their counterparts in the Morris water maze and novel-object recognition tests, behavioral tasks meant to measure learning and memory performance. In the group who had received sevoflurane for 1 hour, significantly less structural and functional damage was observed in the hippocampus. The results demonstrate sevoflurane anesthesia may time-dependently induce cognitive dysfunction by deteriorating hippocampal function.⁴

A similar study on sevoflurane and its effects on hippocampal neurons was conducted on 42 adult rats. Results of an open field test showed decreased locomotor performance for both male and female rats treated with 3% sevoflurane, compared to their control counterparts. However, there was only a significant difference between the experimental and control groups at one day post-anesthesia, but not at 30, 60, or 90 days, indicating sevoflurane inhibits short-term locomotor activities but has little effect on long-term movement.⁵ For their molecular analysis, the researchers collected data on the cAMP response element binding (CREB) protein, a key gene that mediates downstream transcription imitation factors and regulates neuronal survival. Sevoflurane is known to exert its anesthetic effects through inhibition of hippocampal NMDA receptors, which are heavily connected to CREB protein signaling pathways. Western blotting revealed phosphorylation of CREB was significantly decreased at one week following treatment, whereas no distinct difference was detected in the rat hippocampus at three months post-anesthesia.⁵ Sevoflurane was also shown to increase levels of Caspase-3 and Caspase-8, death proteases that are crucial mediators of apoptosis.⁶ Collectively, the results suggest that sevoflurane may induce cognitive dysfunction through inhibiting CREB signaling pathways, which in turn blocks NMDA receptor function.

In general, the existing literature suggests that high levels of exposure to sevoflurane anesthesia may pose risks to cognitive function, possibly through its impact on the hippocampus. Murine studies indicate exposure to sevoflurane can cause neuronal apoptosis and structural damage to the hippocampus. These changes may contribute to post-operative cognitive dysfunction and other neurological deficits concerning learning and memory. However, it is important to note that many of these effects may be short-term, with many individuals recovering their lost cognitive function over time. Nonetheless, the possible time-dependent nature of these effects does not take away from the need for continued research to better understand the duration and reversibility of sevoflurane’s effects on cognitive dysfunction.

References

Bekker, Alex Y., and Edwin J. Weeks. “Cognitive Function after Anaesthesia in the Elderly.” Best Practice & Research Clinical Anaesthesiology, vol. 17, no. 2, June 2003, pp. 259–72. https://doi.org/10.1016/S1521-6896(03)00005-3
Zheng, S. Q., et al. “Sevoflurane Causes Neuronal Apoptosis and Adaptability Changes of Neonatal Rats.” Acta Anaesthesiologica Scandinavica, vol. 57, no. 9, Oct. 2013, pp. 1167–74. https://doi.org/10.1111/aas.12163
Howland, John G., and Yu Tian Wang. “Chapter 8 Synaptic Plasticity in Learning and Memory: Stress Effects in the Hippocampus.” Progress in Brain Research, edited by Wayne S. Sossin et al., vol. 169, Elsevier, 2008, pp. 145–58. https://doi.org/10.1016/S0079-6123(07)00008-8
Xiao, Hongyan, et al. “Learning, Memory and Synaptic Plasticity in Hippocampus in Rats Exposed to Sevoflurane.” International Journal of Developmental Neuroscience, vol. 48, Feb. 2016, pp. 38–49. https://doi.org/10.1016/j.ijdevneu.2015.11.001
Xie, H., et al. “The Gender Difference in Effect of Sevoflurane Exposure on Cognitive Function and Hippocampus Neuronal Apoptosis in Rats.” European Review for Medical and Pharmacological Sciences, vol. 19, no. 4, Feb. 2015, pp. 647–57.
Porter, Alan G., and Reiner U. Jänicke. “Emerging Roles of Caspase-3 in Apoptosis.” Cell Death & Differentiation, vol. 6, no. 2, Feb. 1999, pp. 99–104. https://doi.org/10.1038/sj.cdd.4400476

Different Types of Neuraxial Anesthesia

Neuraxial anesthesia refers to a group of regional anesthesia techniques that involve the administration of anesthetic agents near the central nervous system’s neuraxial axis, specifically within the spinal canal. The primary types of neuraxial anesthesia are spinal anesthesia, epidural anesthesia, and combined spinal-epidural (CSE) anesthesia. Each technique has unique applications, benefits, and considerations, making them essential tools in modern anesthesiology ¹.

Spinal anesthesia involves injecting a local anesthetic into the cerebrospinal fluid within the subarachnoid space, usually between the L3-L4 or L4-L5 vertebrae, with the patient in a sitting or lateral decubitus position. It provides a rapid onset of sensory and motor blockade within 5-10 minutes, lasting 1-3 hours, depending on the anesthetic administered. Spinal anesthesia is commonly used for lower abdominal, pelvic, and lower extremity surgeries, including cesarean sections and hip replacements. Benefits include a predictable blockade and minimal systemic absorption, while risks include hypotension, post-dural puncture headache, and limited duration of action ².

Epidural anesthesia involves the injection of local anesthetics into the epidural space, which is located just outside the dura mater. Though both spinal and epidural anesthesia target the spinal cord, the two types of neuraxial anesthesia differ in how close to the spinal cord medication is injected. In epidural anesthesia, a catheter may be placed in the epidural space to allow continuous or intermittent administration of anesthetics. Epidural anesthesia has a slower onset compared to spinal anesthesia, typically taking 15-30 minutes to establish effective blockade, but it can be prolonged by adjusting the infusion of anesthetics through an epidural catheter. Epidural anesthesia is versatile and used for a wide range of surgeries, including thoracic, abdominal, and lower limb procedures, but also for labor analgesia and postoperative pain control. However, they involve technical complexity, potential for failed block, slower onset, and risks such as epidural hematoma or infection ^3–5.

CSE anesthesia combines the benefits of both spinal and epidural techniques—initially, a spinal needle is inserted through an epidural needle to deliver a single dose of local anesthetic into the subarachnoid space, after which an epidural catheter is placed for continuous or intermittent administration of anesthetics. CSE provides the rapid onset of spinal anesthesia with the prolonged and adjustable duration of epidural anesthesia: the spinal component offers immediate anesthesia, with the epidural catheter maintaining the blockade. CSE anesthesia is particularly useful for procedures requiring immediate and prolonged anesthesia, such as major abdominal surgeries and labor analgesia ^6,7. Advantages include its rapid onset and reliable block from the spinal component, prolonged anesthesia and postoperative analgesia through the epidural catheter, and flexibility. However, it requires a high level of skill and carries risks such as hypotension, post-dural puncture headache, and epidural catheter-related complications ^7,8.

The different types of neuraxial anesthesia are spinal, epidural, and combined spinal-epidural techniques, each offering distinct advantages for various surgical and pain management applications. The choice of neuraxial anesthesia depends on factors such as the type and duration of surgery, patient condition, and desired postoperative pain control.

References

1. Regional Anesthetic Blocks – StatPearls – NCBI Bookshelf. Available at: https://www.ncbi.nlm.nih.gov/books/NBK563238/.

2. Spinal Anesthesia – StatPearls – NCBI Bookshelf. Available at: https://www.ncbi.nlm.nih.gov/books/NBK537299/.

3. Epidural Anesthesia – StatPearls – NCBI Bookshelf. Available at: https://www.ncbi.nlm.nih.gov/books/NBK542219/.

4. Epidural – NHS. Available at: https://www.nhs.uk/conditions/epidural/.

5. Epidural: What It Is, Procedure, Risks & Side Effects. Available at: https://my.clevelandclinic.org/health/treatments/21896-epidural.

6. Roofthooft, E., Rawal, N. & Van de Velde, M. Current status of the combined spinal-epidural technique in obstetrics and surgery. Best Pract. Res. Clin. Anaesthesiol. 37, 189–198 (2023).doi: 10.1016/j.bpa.2023.04.004

7. Combined Spinal Epidural (CSE). Available at: https://www.asra.com/news-publications/asra-updates/blog-landing/legacy-b-blog-posts/2019/08/07/combined-spinal-epidural-(cse).

8. Combined spinal–epidural techniques – Continuing Education in Anaesthesia, Critical Care and Pain. Available at: https://www.bjaed.org/article/S1743-1816(17)30496-1/fulltext.

Learning From the Anesthesia Incident Reporting System

The practice of anesthesia involves the administration of powerful drugs to induce unconsciousness, manage pain, and support vital functions during surgery. Despite advancements in technology and clinical practices, anesthesia-related incidents can and do occur. To mitigate these risks and enhance patient safety, the Anesthesia Incident Reporting System (AIRS) was created to support the collection, analysis, and dissemination of information about anesthesia-related incidents, facilitating continuous learning and improvement in the field.

The Anesthesia Incident Reporting System is designed to capture data on adverse events, near misses, and any other anomalies related to anesthesia. By aggregating data from numerous incidents, AIRS helps identify common patterns and trends that might not be apparent from isolated cases. This can highlight areas where systemic improvements are needed. Understanding the underlying causes of incidents is crucial for preventing recurrence—AIRS facilitates detailed analyses to uncover deeper issues. The insights gained from the Anesthesia Incident Reporting System are then used to drive learning for anesthesia professionals. This ensures that past lessons are incorporated into future practice. Additionally, data from AIRS can inform the development of new policies and protocols, ensuring they are based on real-world evidence and address identified risks effectively ^1,2.

An effective incident reporting system such as AIRS relies on several key components. For the system to be effective, healthcare providers must feel safe reporting incidents without fear of punishment. This spurs comprehensive reporting and ensures that a wide range of data is captured. In addition, protecting the identity of reporters and patients involved in incidents is crucial. Comprehensive documentation of incidents, including the context, sequence of events, and contributing factors, is vital. This allows for a thorough analysis and greater understanding of how and why incidents occur. In parallel, providing feedback to those who report incidents and communicating findings to the wider anesthesia community ensures that lessons are shared and applied broadly ^3,4.

Several case studies and examples illustrate the value of learning from the Anesthesia Incident Reporting System.

Medication Errors

Analysis of AIRS data has revealed that medication errors, such as incorrect drug administration or dosing, are a relatively common type of adverse incident in anesthesia. By understanding the circumstances that lead to these errors, such as look-alike packaging or unclear labeling, strategies can be implemented to reduce their occurrence. This might include implementing barcode scanning or standardized labeling protocols ^5,6.

Airway Management

Incidents related to airway management are another significant concern. Reports from AIRS have highlighted issues such as difficult intubations and unanticipated airway obstructions. Training programs emphasizing advanced airway management techniques and simulation-based education have been developed in response to these findings ^7–9.

Equipment Malfunctions

Data from AIRS have identified equipment malfunctions as a frequent contributor to anesthesia-related incidents. This has led to improved maintenance schedules, regular equipment checks, and the development of more reliable and user-friendly anesthesia machines ^9,10.

The impact of the Anesthesia Incident Reporting System on patient safety cannot be overstated. By fostering a culture of continuous learning and improvement, AIRS has helped reduce preventable anesthesia-related complications. Healthcare facilities that actively engage with AIRS data often report lower rates of adverse events and higher levels of staff confidence in managing anesthesia safely ^11,12.

The Anesthesia Incident Reporting System represents a critical tool in the ongoing effort to enhance patient safety in anesthesia care. By capturing detailed data on incidents, facilitating root cause analysis, and informing education and policy development, AIRS helps healthcare providers learn from past experiences and implement effective strategies to prevent future incidents.

References

1. AQI – Anesthesia Quality Institute. Available at: https://www.aqihq.org/airsIntro.aspx. (Accessed: 20th June 2024)

2. Anesthesia Incident Reporting Systems – Anesthesia Services for Indiana. Available at: https://www.anesthesiaservicesin.com/anesthesia-incident-reporting-systems/. (Accessed: 20th June 2024)

3. The Anesthesia Incident Reporting System (AIRS) – Anesthesia Patient Safety Foundation. Available at: https://www.apsf.org/article/the-anesthesia-incident-reporting-system-airs/. (Accessed: 20th June 2024)

4. Saad, R. & Hanna, J. S. Reporting: Mandatory and Voluntary Systems, Legal Requirements, Anesthesia Quality Institute, and Physician Quality Reporting System. Case Stud. Clin. Psychol. Sci. Bridg. Gap from Sci. to Pract. 1–7 (2023). doi:10.1093/MED/9780197584521.003.0372

5. Mutair, A. Al et al. The Effective Strategies to Avoid Medication Errors and Improving Reporting Systems. Medicines 8, 46 (2021). doi: 10.3390/medicines8090046

6. Anesthesia Incident Reporting System (AIRS): Case 2021-3: All Orders Are Not Alike. ASA Monit. 85, 22–22 (2021).

7. Avva, U., Lata, J. & Kiel, J. Airway Management – StatPearls – NCBI Bookshelf. StatePearlsPublishing (2021).

8. Apfelbaum, J. L. et al. 2022 American Society of Anesthesiologists Practice Guidelines for Management of the Difficult Airway. Anesthesiology (2022). doi:10.1097/ALN.0000000000004002

9. Anesthesia Incident Reporting System (AIRS) Case 2022-08: It’s All About the Airway. What Would You Do? ASA Monit. 86, 10–11 (2022).

10. McIntyre, J. W. R. Anesthesia equipment malfunction: Origins and clinical recognition. Can. Med. Assoc. J. (1979).

11. Arnal-Velasco, D. & Barach, P. Anaesthesia and perioperative incident reporting systems: Opportunities and challenges. Best Practice and Research: Clinical Anaesthesiology (2021). doi:10.1016/j.bpa.2020.04.013

12. Bielka, K. et al. Critical incidents during anesthesia: prospective audit. BMC Anesthesiol. (2023). doi:10.1186/s12871-023-02171-4

Learning From the Anesthesia Incident Reporting System