Category: Uncategorized

Disclaimer: This article is intended solely for informational and educational purposes only. It does not constitute medical advice.

Gastric point-of-care ultrasound (POCUS) is increasingly used to assess gastric contents before anesthesia and procedural sedation. Its clinical value comes from providing direct information about the stomach when fasting history alone may be unreliable and when gastric emptying times may be atypical. Although preoperative fasting reduces aspiration risk, the time since a patient last ate or drank does not always predict whether the stomach is actually empty. Gastric emptying may be delayed by diabetes, gastroparesis, pregnancy, obesity, acute illness, or medications that affect gastrointestinal motility. In these situations, gastric POCUS can help determine whether clinically significant material remains in the stomach and can inform decisions about procedure timing and airway management; however, its usefulness for clinical decision-making depends on its accuracy (1).  

Gastric POCUS focuses on the antrum, the distal portion of the stomach that is most consistently visualized with ultrasound. The sonographic appearance of the antrum changes according to its contents. An empty antrum is typically small or collapsed, while clear liquid appears dark or black (hypoechoic) and relatively uniform. Thick liquids appear brighter (hyperechoic) and more homogeneous, whereas solid food produces a mixed gray-and-bright, heterogeneous “frosted glass” appearance on ultrasound (1). Gastric scanning is usually performed with the patient supine and then in the right lateral decubitus position. In the right lateral position, gravity moves gastric contents toward the antrum, making small volumes easier to detect and enabling more reliable measurements. In this way, gastric POCUS provides both a qualitative assessment of what type of content is present and, under appropriate conditions, a quantitative estimate of gastric fluid volume. 

The qualitative accuracy of gastric POCUS has been evaluated in prospective studies. Kruisselbrink and colleagues found that trained clinicians could use gastric ultrasound to distinguish among different gastric-content states with high diagnostic accuracy (2). This means that the examination is generally reliable for determining whether the stomach is empty or contains liquid or solid material. That qualitative assessment is usually sufficient when solid or thick contents are visualized because their presence already suggests a higher-risk stomach. When only clear liquid is present, however, clinicians must determine how much fluid is in the stomach. 

Gastric POCUS can address this problem quantitatively by measuring the antral cross-sectional area, which is the two-dimensional area of the gastric antrum seen on a standardized ultrasound image. Bouvet and colleagues demonstrated that, generally, when the stomach contains clear fluid, the antrum becomes distended, so a larger antral cross-sectional area is associated with greater amounts of gastric fluid (3). Perlas and colleagues later validated a mathematical model that uses right-lateral antral cross-sectional area together with patient age to estimate total gastric fluid volume (4).  

Despite these advantages, gastric POCUS does not provide a perfect measurement of total gastric content. Volume estimates are most applicable to clear liquids and should not be interpreted as direct measurements of solid or thick material. Accuracy also depends on correct identification of the antrum, proper patient positioning, image quality, and operator experience (4). For this reason, gastric POCUS should be considered as one component of clinical assessment rather than a replacement for fasting history or physician judgment. When performed correctly, it offers a rapid, noninvasive, and reasonably accurate method for identifying gastric contents and estimating clear-fluid volume in patients whose gastric status is uncertain. 

References 

1. Perlas A, Arzola C, Van de Putte P. Point-of-care gastric ultrasound and aspiration risk assessment: a narrative review. Can J Anaesth. 2018;65(4):437-448. doi:10.1007/s12630-017-1031-9 

2. Kruisselbrink R, Gharapetian A, Chaparro LE, et al. Diagnostic Accuracy of Point-of-Care Gastric Ultrasound. Anesth Analg. 2019;128(1):89-95. doi:10.1213/ANE.0000000000003372

3. Bouvet L, Mazoit JX, Chassard D, Allaouchiche B, Boselli E, Benhamou D. Clinical assessment of the ultrasonographic measurement of antral area for estimating preoperative gastric content and volume. Anesthesiology. 2011;114(5):1086-1092. doi:10.1097/ALN.0b013e31820dee48 

4. Perlas A, Mitsakakis N, Liu L, et al. Validation of a mathematical model for ultrasound assessment of gastric volume by gastroscopic examination. Anesth Analg. 2013;116(2):357-363. doi:10.1213/ANE.0b013e318274fc19

Disclaimer: This article is intended solely for informational and educational purposes only. It does not constitute medical advice.

Bradycardia is generally defined in adults as a heart rate below 60 beats per minute. Although it is a normal physiologic finding in some healthy individuals, particularly athletes and those with high vagal tone, it may also signal cardiovascular instability in the perioperative setting. The anesthesiologist’s challenge is therefore not simply recognizing a low heart rate but determining whether it is compromising cardiac output and tissue perfusion. Patients who remain hemodynamically stable may require little more than observation, whereas bradycardia accompanied by hypotension, myocardial ischemia, or other signs of poor perfusion is clinically significant for anesthesia management and requires prompt evaluation and treatment to prevent progression to cardiovascular collapse (1). 

Effective management of bradycardia begins with a thorough preoperative assessment. Determining whether bradycardia is a chronic, asymptomatic finding or the result of underlying cardiac disease helps guide anesthetic planning and intraoperative monitoring. A review of the patient’s cardiovascular history, previous electrocardiograms, anesthetic records, and medications can identify those at increased risk for clinically significant bradycardia during surgery. Particular attention should be given to medications that suppress sinoatrial or atrioventricular nodal function, including beta-blockers, calcium channel blockers, and digoxin, as these drugs may amplify the cardiovascular effects of anesthetic agents (1). Patients with known conduction abnormalities or implanted cardiac devices may require additional preoperative evaluation and individualized perioperative planning (2). 

Although anesthesia commonly produces modest reductions in heart rate, clinically significant bradycardia usually occurs when anesthetic-induced changes in autonomic tone are combined with other physiologic stresses. Most anesthetic agents decrease sympathetic activity while allowing parasympathetic influences to predominate, making patients more susceptible to vagally mediated reflexes. Consequently, airway manipulation, ocular traction, surgical stimulation, and spinal anesthesia can all precipitate abrupt decreases in heart rate, particularly when venous return is reduced. In some patients, diminished preload activates reflex pathways such as the Bezold-Jarisch reflex, producing profound bradycardia, hypotension, and, in rare cases, transient asystole. Understanding these mechanisms allows the anesthesia team to anticipate periods of increased risk and intervene before significant hemodynamic deterioration occurs (3). 

Because bradycardia is often a manifestation of another physiologic disturbance rather than the primary problem itself, treatment should focus first on identifying and correcting reversible causes. Improving oxygenation and ventilation, reducing excessive anesthetic depth, restoring intravascular volume when appropriate, and eliminating ongoing vagal stimulation may resolve the arrhythmia without additional intervention. If the patient remains symptomatic or develops hypotension despite these measures, pharmacologic therapy is indicated. Atropine remains the treatment of choice for most episodes of vagally mediated bradycardia, while vasopressors such as ephedrine or epinephrine may be required when circulatory compromise is more pronounced. Patients with persistent bradycardia caused by advanced conduction disease or those who fail to respond to medical therapy may ultimately require temporary cardiac pacing (1). 

Successful anesthesia management of patients with bradycardia depends on understanding and addressing the physiology responsible for the rhythm disturbance. Careful preoperative assessment, anticipation of high-risk situations, and prompt correction of reversible causes allow most episodes of perioperative bradycardia to be managed before serious complications develop, improving both cardiovascular stability and overall perioperative outcomes. 

References 

1. Watterson LM, Morris RW, Westhorpe RN, Williamson JA. Crisis management during anaesthesia: bradycardia. Qual Saf Health Care. 2005;14(3):e9. doi:10.1136/qshc.2002.004481 

2. Staikou C, Chondrogiannis K, Mani A. Perioperative management of hereditary arrhythmogenic syndromes. Br J Anaesth. 2012;108(5):730-744. doi:10.1093/bja/aes105 
3. Campagna JA, Carter C. Clinical relevance of the Bezold-Jarisch reflex. Anesthesiology. 2003;98(5):1250-1260. doi:10.1097/00000542-200305000-00030 

Ketamine is an incredibly versatile drug that can act as an anesthetic, analgesic, antidepressant, and psychedelic, depending on the dose and clinical context. It can provide pain relief and clinical sedation but may also produce dissociative and perceptual effects, ranging from altered sensations of time and space to feelings of derealization and depersonalization.¹ 

These psychoactive effects can put restraints on patient acceptance and generally limit the use of ketamine in pain management. As a result, an important question is whether ketamine’s analgesic and psychedelic effects arise from the same underlying neural mechanisms or if they represent distinct pharmacological processes. Understanding this relationship could help guide the development of treatments that retain analgesic efficacy while minimizing unwanted psychological effects.² 

A randomized, double-blind crossover trial of 20 healthy male volunteers administered increasing intravenous doses of either S-ketamine or racemic ketamine over a 3-hour period. Throughout the experiment, researchers measured pain sensitivity using a pressure pain threshold test and assessed psychedelic effects using the Bowdle questionnaire, which is known to evaluate changes in perception such as altered body image, distorted surroundings, and the perception of time. Blood samples were also collected at regular intervals to measure plasma concentrations of ketamine and its primary metabolite, norketamine.¹ 

The researchers then used population pharmacokinetic-pharmacodynamic modeling to examine the relationship between ketamine concentrations in the blood and both analgesic and psychedelic effects over time. Several in-depth mathematical models were developed to estimate the potency, onset, and offset of ketamine’s effects on pain relief and altered perception while accounting for individual variability between participants. Additionally, the analysis investigated whether norketamine contributed to or modified ketamine’s effects¹ 

The pharmacodynamic modeling showed that ketamine’s analgesic and dissociative effects were best explained by a single model with shared parameters. The researchers found no significant differences in potency or onset/offset times between pain relief, as measured by pressure pain threshold, and dissociation, as measured by changes in external perception. Similarly, there were no meaningful differences between S-ketamine and racemic ketamine. Interestingly, adding S-norketamine, a ketamine metabolite, significantly improved the model fit, suggesting it influences ketamine’s effects, whereas R-ketamine and R-norketamine appeared to contribute little to either analgesia or dissociation.¹ 

Overall, the results suggest that ketamine-induced analgesia and dissociation are closely linked and may arise from common underlying mechanisms. The similar concentration-effect relationships and time courses for the two outcomes indicate that the same pharmacological processes may drive both the analgesic and psychedelic effects of ketamine. These findings contrast with some previous studies that reported little association between ketamine’s analgesic and dissociative effects, but it may be the case that those studies used much higher ketamine doses and less detailed pharmacokinetic analyses.^3-5 This study suggests that ketamine’s analgesic and psychedelic effects may not be easily separable. 

Remarkably similar potency and time-course parameters for pain relief and altered perception have been found between the analgesic and psychedelic effects of ketamine, supporting an association between the two. While the results suggest that ketamine-induced analgesia and dissociation may arise from interconnected neural processes, perhaps from the thalamus and/or limbic system, further research can help determine whether a direct functional dependency exists between the brain networks underlying these effects. 

References 

1. Olofsen, E., Kamp, J., Henthorn, T.K., et al. Ketamine Psychedelic and Antinociceptive Effects are Connected. Anesthesiology 2022; 136:792–801. https://doi.org/10.1097/aln.0000000000004176  

2. Mashour, G.A., Ketamine Analgesia and Psychedelia: Can We Dissociate Dissociation? Anesthesiology. 2022;136(5):675-677. https://doi.org/10.1097/aln.0000000000004172  

3. Gitlin, J., Chamadia, S., Locascio, J. J., Ethridge, B. R., Pedemonte, J.C., Hahm, E.Y., Ibala, R., Mekonnen, J., Colon, K.M., Qu, J., Akeju, O., Dissociative and Analgesic Properties of Ketamine are Independent. Anesthesiology 2020; 133:1021–8 

4. Jonkman, K., van der Schrier, R., van Velzen, M., Aarts, L., Olofsen, E., Sarton, E., Niesters, M., Dahan, A., Differential Role of Nitric Oxide in the Psychedelic Symptoms Induced by Racemic Ketamine and Esketamine in Human Volunteers. Br J Anaesth 2018; 120:1009–18 

5. Hahm, E.Y., Chamadia, S., Locascio, J.J., Pedemonte, J.C., Gitlin, J., Mekonnen, J., Ibala, R., Ethridge, B.R., Colon, K.M., Qu, J., Akeju, O. Dissociative and Analgesic Properties of Ketamine are Independent and Unaltered by Sevoflurane General Anesthesia. Pain Rep 2021; 6:e936. https://doi.org/10.1097/pr9.0000000000000936  

Peripheral nerve blocks are widely used in regional anesthesia to provide postoperative analgesia while reducing opioid consumption and opioid-related side effects. The duration of analgesia with single-shot nerve blocks, however, is limited by the pharmacologic properties of local anesthetics. To prolong block duration and improve postoperative pain control, anesthesiologists frequently use adjuvant medications, with dexamethasone being among the most studied. Dexamethasone may be administered through either a perineural (adjacent to the targeted nerve) or intravenous (IV) route when used as an adjunct for peripheral nerve block. Considerable research has focused on determining whether one route offers superior analgesic outcomes. 

Dexamethasone is a corticosteroid with potent anti-inflammatory and analgesic properties. Proposed mechanisms for prolonging nerve blockade include suppression of inflammatory mediators, reduction of ectopic neuronal discharge, and modulation of potassium channel activity in nociceptive fibers. Perineural administration was initially believed to exert a stronger local effect by acting directly at the nerve site. However, the observation that IV dexamethasone also prolongs block duration raised the possibility that systemic anti-inflammatory effects may account for much of the clinical benefit. 

Numerous randomized controlled trials and meta-analyses have compared how perineural and IV dexamethasone administration extend the duration of peripheral nerve block. Most studies demonstrate that both routes significantly prolong sensory block duration and postoperative analgesia compared with placebo. However, perineural dexamethasone is generally reported to produce a longer duration of analgesia than IV administration, potentially lasting two to three hours longer. Other research suggests modest increases in sensory and motor block with the perineural route. In addition, some investigations have shown slightly lower postoperative pain scores and reduced opioid requirements. 

Despite these findings, the clinical significance of the difference remains controversial. While the prolongation associated with perineural administration may reach statistical significance, many clinicians question whether a relatively small increase in analgesic duration meaningfully changes patient outcomes. Intravenous dexamethasone provides many of the same benefits without requiring off-label injection around peripheral nerves. IV administration also offers the added advantage of reducing postoperative nausea and vomiting, which may improve overall patient satisfaction and recovery. 

Safety considerations continue to influence practice patterns. Current evidence has not demonstrated definitive neurotoxicity associated with perineural dexamethasone, and randomized trials have generally reported low complication rates. Nevertheless, concerns remain because long-term safety data are limited and perineural corticosteroid administration remains off-label in many countries. Some clinicians therefore favor IV dexamethasone because it avoids direct exposure of peripheral nerves to corticosteroids while still providing substantial analgesic prolongation. 

Dose optimization of dexamethasone through these routes has also been studied extensively. Research suggests that both IV and perineural dexamethasone exhibit ceiling effects, meaning that increasing doses beyond a certain point does not have additional benefits on the peripheral nerve block. Most studies support the use of low-to-moderate doses to balance efficacy with minimization of systemic corticosteroid exposure. Variability in study design, local anesthetic selection, surgical procedures, and nerve block techniques has contributed to some inconsistency in the literature, but the overall evidence supports the effectiveness of both administration routes. 

References 

1. Tan ESJ, Tan YR, Liu CWY. Efficacy of perineural versus intravenous dexamethasone in prolonging the duration of analgesia when administered with peripheral nerve blocks: a systematic review and meta-analysis. Korean J Anesthesiol. 2022;75(3):255-265. 

2. Baeriswyl M, Kirkham KR, Jacot-Guillarmod A, Albrecht E. Efficacy of perineural vs systemic dexamethasone to prolong analgesia after peripheral nerve block: a systematic review and meta-analysis. Br J Anaesth. 2017;119(2):183-191. 

3. Heesen M, Klimek M, Imberger G, et al. Co-administration of dexamethasone with peripheral nerve block: intravenous vs perineural application: systematic review, meta-analysis, meta-regression and trial-sequential analysis. Br J Anaesth. 2018;120(2):212-227. 

4. Chong MA, Berbenetz NM, Lin C, Singh S. Perineural versus intravenous dexamethasone as an adjuvant for peripheral nerve blocks: a systematic review and meta-analysis. Reg Anesth Pain Med. 2017;42(3):319-326. 

5. Zufferey PJ, Chaux R, Lachaud PA, et al. Dose-response relationships of intravenous and perineural dexamethasone as adjuvants to peripheral nerve blocks: a systematic review and model-based network meta-analysis. Br J Anaesth. 2024;132(5):1122-1132. 

Fasting is a physiological state characterized by the absence of caloric intake that prompts the body to shift its metabolic and hemodynamic processes to maintain homeostasis. Both short-term fasting, such as pre-anesthetic fasting, and extended fasting, such as during religious observances, induce adaptive responses and metabolic and hemodynamic changes that are relevant for perioperative care. A review of medical literature highlights important differences and similarities in how the body responds across these time frames, with implications for clinical care and patient safety.

During short-term fasting, typically lasting 6–12 hours before anesthesia, the body primarily relies on glycogen stores to maintain blood glucose levels. Hepatic glycogenolysis becomes the dominant metabolic pathway, ensuring a steady supply of glucose to vital organs, particularly the brain. Insulin levels decrease, while glucagon levels rise, facilitating the mobilization of glucose. These metabolic adjustments are generally well tolerated in healthy individuals, with minimal disruption to overall energy balance.

Hemodynamically, short-term fasting has limited effects in most patients. Blood pressure and heart rate typically remain stable, although mild dehydration may occur if fluid intake is also restricted. This is particularly relevant in preoperative settings, where fasting guidelines aim to reduce the risk of aspiration while minimizing hemodynamic instability. Studies suggest that allowing clear fluids up to a few hours before surgery can help preserve intravascular volume and reduce perioperative hypotension.

In contrast, extended fasting, such as during religious practices like Ramadan, involves longer periods without food and sometimes fluids that may be repeated daily over several weeks. In such cases of fasting, patients experience greater metabolic and hemodynamic changes, with implications for medical care, especially regarding surgery. As glycogen stores become depleted, the body transitions to alternative energy sources, primarily through gluconeogenesis and lipolysis. Fatty acids are mobilized and converted into ketone bodies, which serve as an important energy substrate for the brain during prolonged fasting. This metabolic shift reflects a state of increased fat utilization and decreased reliance on glucose.

Extended fasting also produces more pronounced hormonal changes. Levels of cortisol and growth hormone may increase, supporting energy mobilization and maintaining blood glucose levels. Meanwhile, insulin sensitivity often improves, which has been associated with beneficial metabolic outcomes in some populations. However, these effects can vary depending on individual health status, duration of fasting, and dietary patterns during non-fasting periods.

Hemodynamic changes during extended fasting are more variable and can be influenced by hydration status. In cases where fluid intake is restricted, individuals may experience reductions in plasma volume, leading to decreases in blood pressure and potential orthostatic hypotension. Heart rate may increase as a compensatory mechanism to maintain cardiac output. In healthy individuals, these changes are usually mild and well tolerated, but they may pose risks for patients with cardiovascular conditions or those taking antihypertensive medications.

In clinical practice, understanding these distinctions is essential. Preoperative fasting protocols must balance safety with patient comfort and physiological stability, while clinicians caring for individuals observing extended fasting should consider potential impacts on metabolism, hydration, and cardiovascular function. Tailored medical guidance is particularly important for vulnerable populations, including those with diabetes, cardiovascular disease, or other chronic conditions.

In conclusion, fasting—whether short-term or extended—triggers a spectrum of metabolic and hemodynamic changes designed to preserve energy balance and organ function. While short-term fasting is generally well tolerated with minimal physiological disturbance, extended fasting leads to more substantial adaptations, including shifts toward fat metabolism and potential cardiovascular effects. Awareness of these changes is critical for optimizing patient care across both medical and cultural contexts.

References

1. Longo VD, Mattson MP. Fasting: Molecular mechanisms and clinical applications. Cell Metab. 2014;19(2):181-192. https://doi.org/10.1016/j.cmet.2013.12.008

2. Cahill GF Jr. Fuel metabolism in starvation. Annu Rev Nutr. 2006;26:1-22. https://doi.org/10.1146/annurev.nutr.26.061505.111258

3. Practice guidelines for preoperative fasting. Anesthesiology. 2017;126(3):376-393. https://doi.org/10.1097/aln.0000000000001452

4. Trepanowski JF, Bloomer RJ. The impact of religious fasting on human health. Nutr J. 2010;9:57. https://doi.org/10.1186/1475-2891-9-57

5. Norouzy A, et al. Effect of Ramadan fasting on cardiovascular risk factors. J Nutr Metab. 2013;2013:742617. https://doi.org/10.1186/1475-2891-11-69

Trends in tobacco use in the US have shifted dramatically over the past half century, thanks, in part, to improved scientific and medical knowledge, policies aimed at reducing cigarette use, and the emergence of tobacco-free products like electronic cigarettes (e-cigarettes). Although these trends demonstrate how major strides can be made in public health in a matter of decades, there still remains a need to strengthen public health protections around tobacco use.

Epidemiological cohort studies (in which groups of people are followed for a long time to measure the impact of exposure to a specific factor) providing clear evidence of the link between cigarette smoking and lung cancer were first conducted in the 1950s.¹ Around that time, the majority of US adults were smokers: smoking prevalence was 56.9% in 1955.² Public opinion and behavior, however, began to shift after the release of the 1964 US Surgeon General Report, which concluded that the average smoker had a 9- to 10-fold increased risk of developing lung cancer compared to non-smokers, while smoking was responsible for a 70% increased mortality rate among smokers versus non-smokers.³ Smoking prevalence dropped shortly thereafter. Among US adults, it was 42.4% in 1965 but fell to 33.2% by 1980; by 2022, it was only 11.6%, according to data from the American Lung Association.⁴ According to one study, over 8 million US deaths attributable to smoking have been averted since 1964.⁵

Increased taxes on tobacco products, the introduction of smoking bans to places like workplaces and restaurants, restrictions on advertising, and increased support for smoking cessation have all contributed to the dramatic decline in tobacco use in the US. The trends also hold true for adolescents. In 1997, 36.4% of US high school students reported smoking cigarettes, but only 3.8% did in 2021.⁴ Between 1991 and 2021, daily cigarette use decreased from 9.8% to 0.6%, while frequent use—defined as smoking on 20 or more days during the 30 days before the survey—dropped from 12.7% to 0.7%.⁶

In recent years, however, the trend of decreased tobacco use in the US has been matched—and in some ways even exceeded—by a trend towards increased use of e-cigarettes. Though they do not contain tobacco, most e-cigarette products contain nicotine, which is often extracted from the tobacco plant, and carry a range of health risks, including lung injury, nicotine addiction, and harms to brain development in adolescents.⁷ According to data from the Centers for Disease Control and Prevention, whereas only 4.5% of US adults used e-cigarettes in 2019, 6.5% did so in 2023.⁸

Additionally, between 2017 and 2023, the number of US adults who exclusively smoke cigarettes decreased by 6.8 million, but the number of US adults who exclusively use e-cigarettes increased by 7.2 million.⁹ E-cigarette usage among adolescents surged in the 2010s, reaching a peak of 27.5% among high school students in 2019¹⁰; in 2024, only 5.9% of US youths reported e-cigarette usage,¹¹ but it still remains a serious public health concern. Though the trend of reduced tobacco smoking among the US population remains a public health achievement, the newer trend of increased e-cigarette usage demands attention and intervention.

References

1. Di Cicco, M. E., Ragazzo, V. & Jacinto, T. Mortality in relation to smoking: the British Doctors Study. Breathe (Sheff) 12, 275–276 (2016), PMID: 28210302

2. Stone, M. D. et al. State and Sociodemographic Trends in US Cigarette Smoking With Future Projections. JAMA Netw Open 8, e256834 (2025), DOI:10.1001/jamanetworkopen.2025.6834

3. The 1964 Report on Smoking and Health. Reports of the Surgeon General – Profiles in Science https://profiles.nlm.nih.gov/spotlight/nn/feature/smoking (2019).

4. American Lung Association. Tobacco Trends Brief: Overall Tobacco Trends Brief. https://www.lung.org/research/trends-in-lung-disease/tobacco-trends-brief/overall-smoking-trends.

5. Holford, T. R. et al. Tobacco Control and the Reduction in Smoking-Related Premature Deaths in the United States, 1964-2012. JAMA 311, 164–171 (2014), DOI: 10.1001/jama.2013.285112

6. Mejia, M. C., Adele, A., Levine, R. S., Hennekens, C. H. & Kitsantas, P. Trends in Cigarette Smoking Among United States Adolescents. Ochsner J 23, 289–295 (2023), DOI: 10.31486/toj.23.0113

7. CDC. Health Effects of Vaping. Smoking and Tobacco Use https://www.cdc.gov/tobacco/e-cigarettes/health-effects.html (2025).

8. Products – Data Briefs – Number 524 – January 2025. https://www.cdc.gov/nchs/products/databriefs/db524.htm (2025) doi:10.15620/cdc/174583.

9. Arrazola, R. A. Notes from the Field: Tobacco Product Use Among Adults — United States, 2017–2023. MMWR Morb Mortal Wkly Rep 74, (2025), DOI: 10.15585/mmwr.mm7407a3

10. Cullen, K. A. et al. e-Cigarette Use Among Youth in the United States, 2019. JAMA 322, 2095–2103 (2019), DOI: 10.1001/jama.2019.18387

11. Commissioner, O. of the. Youth E-Cigarette Use Drops to Lowest Level in a Decade. FDA https://www.fda.gov/news-events/press-announcements/youth-e-cigarette-use-drops-lowest-level-decade (2024).

Endotracheal intubation is a common but often challenging part of anesthetic and critical care, marked by a high risk of hypoxemia. Traditionally, oxygenation during intubation has relied on bag-mask ventilation (BMV) or other forms of positive-pressure ventilation between induction and laryngoscopy. However, there is growing interest in high-flow nasal oxygenation (HFNO) as an alternative to ventilation, particularly for apneic oxygenation during intubation.

High-flow nasal oxygenation delivers warmed, humidified oxygen at flow rates typically ranging from 30 to 70 L/min via wide-bore nasal cannula. This approach provides several physiological advantages, including washout of nasopharyngeal dead space, generation of low-level positive airway pressure, and continuous delivery of oxygen during apnea. High-flow nasal oxygenation may extend safe apnea time and reduce the risk of desaturation, thus facilitating intubation attempts.

Multiple randomized and observational studies in operating room, emergency department, and intensive care unit settings have demonstrated that HFNO improves oxygen saturation during intubation compared with standard low-flow oxygen delivery. In patients with anticipated difficult airways or mild-to-moderate hypoxemia, HFNO has been shown to delay desaturation and increase first-pass intubation success by maintaining higher oxygen reserves. Its hands-free nature also facilitates airway manipulation and may reduce gastric insufflation compared with positive-pressure mask ventilation.

However, high-flow nasal oxygen does not provide ventilation or carbon dioxide clearance during apnea, which is sometimes necessary during intubation. In patients with severe hypoxemia, obesity, or high oxygen consumption, oxygenation alone may be insufficient, and rapid desaturation can still occur. Additionally, HFNO may be less effective in cases of upper airway obstruction or poor nasal patency. Other studies on this approach have shown mixed results, with a 2015 randomized trial demonstrating that HFNO did not make a significant difference in lowest oxygen saturation during intubation in critically ill patients with acute respiratory failure.

Bag-mask ventilation remains a reliable method for both oxygenation and ventilation during intubation, particularly in patients with severe hypoxemia or hypercapnia. When performed with appropriate technique and airway adjuncts, BMV can effectively maintain oxygenation and carbon dioxide elimination. Concerns regarding aspiration risk with positive-pressure ventilation have been challenged by evidence suggesting that gentle ventilation with low inspiratory pressures does not significantly increase aspiration events and may reduce hypoxemia-related complications.

In elective surgical patients with adequate preoxygenation and low risk of complications, HFNO may be used as a primary strategy for apneic oxygenation during rapid sequence induction. However, many patients—particularly those who are hypoxemic or have comorbidities that increase the risk of desaturation—may benefit more from active ventilation using bag-mask ventilation, noninvasive ventilation, or a combination of high-flow nasal oxygenation with assisted ventilation prior to intubation. Some studies suggest that combining HFNO with noninvasive ventilation during preoxygenation offers superior oxygenation compared with either technique alone.

High-flow nasal oxygenation and conventional ventilation during intubation have distinct advantages and limitations. HFNO is particularly useful for extending safe apnea time and maintaining oxygenation during laryngoscopy, while bag-mask ventilation provides more reliable gas exchange in high-risk patients. Optimal airway management should be tailored to patient physiology, clinical setting, and operator expertise, rather than relying on a single universal strategy.

References

1. Patel A, Nouraei SA. Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia. 2015;70(3):323-329. DOI: 10.1111/anae.12923

2. Miguel-Montanes R, Hajage D, Messika J, et al. Use of high-flow nasal cannula oxygen therapy to prevent desaturation during tracheal intubation of ICU patients. Am J Respir Crit Care Med. 2015;193(10):1140-1147. DOI: 10.1097/CCM.0000000000000743

3. Casey JD, Janz DR, Russell DW, et al. Bag-mask ventilation during tracheal intubation of critically ill adults. N Engl J Med. 2019;380(9):811-821. DOI: 10.1056/NEJMoa1812405

4. Semler MW, Janz DR, Lentz RJ, et al. Randomized trial of apneic oxygenation during endotracheal intubation of critically ill patients. Am J Respir Crit Care Med. 2016;193(3):273-280. DOI: 10.1164/rccm.201507-1294OC

5. Frat JP, Thille AW, Mercat A, et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372(23):2185-2196. DOI: 10.1056/NEJMoa1503326

Neuromuscular blockade is an anesthetic technique that allows clinicians to immobilize patients in a controlled way and safely perform precise, complex surgery. Nondepolarizing neuromuscular blocking agents (NMBAs) such as rocuronium and vecuronium produce paralysis by competitively inhibiting nicotinic acetylcholine receptors (nAChRs) at the motor endplate, preventing acetylcholine (ACh) from activating the receptor to generate muscle contraction. Agents used for the reversal of neuromuscular blockade operate through two fundamentally different molecular strategies: boosting synaptic ACh by inhibiting acetylcholinesterase (AChE) or directly removing aminosteroid NMBAs from circulation through host-guest encapsulation. Each method has distinct molecular targets, kinetics, and side-effect profiles that shape clinical use and guide ongoing drug development.¹

AChE contains two key functional regions: an anionic site that attracts the positively charged ammonium of ACh and an esteratic site that catalyzes hydrolysis. Neostigmine is a neuromuscular blockade reversal agent that works on a molecular level by inhibiting AChE, allowing ACh to build up and disrupt the competitive inhibition of the blocking agent. It is a quaternary ammonium carbamate that binds deep within the enzyme’s gorge, occupying both the anionic and esteratic domains. This interaction forms a carbamylated enzyme intermediate that is hydrolyzed far more slowly than the natural substrate.¹ As long as the esteratic site remains carbamylated, ACh cannot access the catalytic machinery, effectively inhibiting AChE until spontaneous decarbamylation restores activity.¹

By inhibiting AChE, neostigmine prolongs the synaptic lifetime of ACh and raises its steady-state concentration at the neuromuscular junction. Elevated ACh then competes more effectively with nondepolarizing NMBAs for nAChR binding. As circulating NMBA levels fall through redistribution and elimination, ACh occupancy of the receptor increases, allowing endplate potentials to return above the threshold needed for muscle contraction.¹ However, this approach is limited by a ceiling effect: once AChE is maximally inhibited, additional drug provides no further benefit, especially in deep blockade. Muscarinic side effects—bradycardia, secretions, bronchospasm—require co-administration of anticholinergics.

Host-guest encapsulation offers a fundamentally different molecular mechanism for neuromuscular blockade reversal. Sugammadex, a modified γ-cyclodextrin, features a hydrophobic central cavity and negatively charged exterior groups. The cavity fits the hydrophobic steroid backbone of rocuronium and vecuronium, while the outer charges attract their cationic regions, enabling tight but reversible 1:1 binding.^{2, 3} Molecular simulations show that rocuronium first docks near the rim of sugammadex, then rotates and slides into the cavity to reach a low-energy, stable configuration.³

Clinically, sugammadex rapidly decreases the free plasma concentration of rocuronium or vecuronium by encapsulating them. This creates a concentration gradient that draws more NMBA molecules away from the neuromuscular junction and into the bloodstream. Once removed from the receptor environment, paralysis resolves without needing to increase ACh levels or inhibit AChE.³

Calabadions represent the next generation of encapsulating agents. These pumpkin-shaped molecular “containers,” derived from the cucurbituril family, bind multiple classes of cationic NMBAs, including steroidal and benzylisoquinolinium drugs.² Calabadion 1 has affinity comparable to the sugammadex–rocuronium complex, while calabadion 2 exhibits dramatically higher binding strength—approximately two orders of magnitude greater than sugammadex in

experimental systems. In vitro and ex vivo studies show calabadion 2 binds rocuronium with roughly 89-fold higher affinity than sugammadex.^2,4 Its adjustable cavity size allows encapsulation of benzylisoquinoliniums like cisatracurium, expanding its therapeutic reach beyond what sugammadex can achieve.^2,4

These complexes are cleared renally, and animal studies demonstrate that calabadion 2 reverses neuromuscular block more rapidly and at lower doses than sugammadex, without major cardiovascular effects.^2,4 Because calabadions do not rely on increasing ACh, they avoid muscarinic adverse effects and the ceiling limitation of AChE inhibitors, and they may work even in profound blockade. Their main barriers to clinical adoption include defining dosing in relation to NMBA burden, assessing off-target binding to other cationic drugs, and establishing human safety. Current evidence remains preclinical, but if validated, calabadions could function as broad—potentially universal—NMBA reversal agents.

The molecular mechanisms behind neuromuscular blockade reversal define both the strengths and limits of current therapy. Traditional AChE inhibitors like neostigmine boost synaptic acetylcholine. However, they only work when NMBA levels are low, and they bring muscarinic side effects and a ceiling on efficacy. Encapsulation agents such as sugammadex mark a real shift: by directly sequestering NMBAs, they allow rapid, reliable reversal even from deep block with fewer autonomic complications. Emerging calabadions may extend this model further, potentially offering universal reversal across NMBA classes.

References

1. Ji W, Zhang X, Liu J, et al. Efficacy and safety of neostigmine for neuromuscular blockade reversal in patients under general anesthesia: a systematic review and meta-analysis. Ann Transl Med. 2021;9(22):1691. doi:10.21037/atm-21-5667

2. Haerter F, Simons JCP, Foerster U, et al. Comparative effectiveness of calabadion and sugammadex to reverse non-depolarizing neuromuscular blocking agents. Anesthesiology. 2015;123(6):1337-1349. doi:10.1097/ALN.0000000000000868

3. Irani AH, Voss L, Whittle N, Sleigh JW. Encapsulation Dynamics of Neuromuscular Blocking Drugs by Sugammadex. Anesthesiology. 2023;138(2):152-163. doi:10.1097/ALN.0000000000004442

4. de Boer HD, Carlos RV. New drug developments for neuromuscular blockade and reversal: Gantacurium, CW002, CW011, and calabadion. Curr Anesthesiol Rep. 2018;8(1):119-124. doi:10.1007/s40140-018-0262-9

Blood pressure measurement is essential to clinical care, especially in surgical and intensive care settings. However, measured values can vary markedly depending on the method used. Differences in device technology, measurement environment, user technique, and physiologic factors all contribute to this variability. Understanding potential variation in blood pressure measurement across measurement methods is important for interpreting readings accurately and selecting the most appropriate monitoring strategy for each patient.

Office blood pressure measurement, traditionally performed by auscultation or automated oscillometric devices, has been the foundation of hypertension diagnosis for decades. Despite its widespread use, office blood pressure often overestimates a patient’s usual blood pressure because of the white-coat effect, improper technique, or suboptimal conditions such as talking or inadequate rest before measurement. Although office readings are standardized and performed by trained personnel, they capture only a brief moment in time and may not reflect typical blood pressure patterns during daily life.

Home blood pressure monitoring (HBPM) provides a more realistic assessment of blood pressure under everyday conditions. Measurements taken at home are typically 5 to 15 mmHg lower than office values due to reduced sympathetic activation and greater patient comfort. HBPM improves diagnostic accuracy for hypertension and enhances long-term management by allowing patients and clinicians to track trends. Accuracy, however, depends on using a validated device, correct cuff size, proper arm positioning, and adherence to measurement protocols.

Ambulatory blood pressure monitoring (ABPM) is considered the gold standard for evaluating true blood pressure patterns. ABPM measures blood pressure at regular intervals over 24 hours, capturing daytime and nighttime values and revealing circadian patterns. Normal individuals experience a 10% to 20% dip in nighttime blood pressure; deviations such as non-dipping or reverse-dipping patterns have been associated with increased cardiovascular morbidity. ABPM is particularly valuable for diagnosing masked hypertension, assessing resistant hypertension, and evaluating treatment effectiveness. Limitations include patient discomfort from repeated cuff inflations and limited accessibility in some clinical settings.

Wrist and finger monitoring methods, sometimes used in nonclinical environments, should generally not be considered accurate to true blood pressure as they produce significant variation in measurement results. Wrist monitors are sensitive to positioning, and inaccurate readings often result when the wrist is not held at heart level. Finger devices rely on photoplethysmographic

measurements and are affected by peripheral vasoconstriction or poor perfusion, making them unreliable for clinical decision-making. For accurate assessment, upper-arm devices remain the preferred noninvasive option.

Invasive arterial blood pressure monitoring provides continuous, beat-to-beat measurements through an arterial catheter and is used primarily in intensive care and surgical settings. Although invasive measurements tend to show slightly higher systolic and lower diastolic pressures than noninvasive cuff methods due to waveform amplification, they offer unmatched accuracy and responsiveness to hemodynamic changes. Risks such as thrombosis, bleeding, and infection restrict invasive monitoring to high-acuity settings.

Variations in blood pressure readings across measurement methods highlight the need for careful interpretation and selection of the most reliable approach for each clinical situation. While office measurements remain important for diagnostic pathways, HBPM and ABPM provide superior insight into true blood pressure patterns and cardiovascular risk, while intensive care and surgery may require the greater precision and accuracy offered by invasive monitoring. Ensuring proper technique and awareness of method-specific limitations is essential to achieving accurate and clinically meaningful blood pressure assessment.

References

1. Pickering TG, Miller NH, Ogedegbe G, et al. Call to action on use and reimbursement for home blood pressure monitoring: a joint scientific statement. Hypertension. 2008;52(1):10-29. DOI: 10.1161/HYPERTENSIONAHA.107.189011

2. O’Brien E, Parati G, Stergiou G, et al. European Society of Hypertension position paper on ambulatory blood pressure monitoring. J Hypertens. 2013;31(9):1731-1768. DOI: 10.1097/HJH.0b013e328363e964

3. Stergiou GS, Palatini P, Asmar R, et al. Recommendations for home blood pressure monitoring. Eur Heart J. 2021;42(39):4007-4020. DOI: 10.1111/jch.13815

4. Sharman JE, Howes F, Head GA, McGrath BP, Stowasser M, Schlaich M. Home and ambulatory blood pressure monitoring: recent evidence and clinical relevance. Med J Aust. 2015;203(3):106-109. DOI: 10.1111/j.1751-7176.2008.00043.x

5. Wax DB, Lin H-M, Leibowitz AB. Invasive and noninvasive blood pressure monitoring: when are both needed? Anesthesiology. 2010;112(3):707-722. DOI: 10.3389/fmed.2017.00202

Normal saline (0.9% sodium chloride) has traditionally been considered the standard isotonic solution for fluid resuscitation and maintenance. Yet, substantial evidence indicates that large-volume administration of normal saline can produce a non-anion gap, hyperchloremic metabolic acidosis that disrupts both acid-base equilibrium and organ perfusion (1). Once regarded as a benign biochemical effect, this iatrogenic acidosis is now recognized as clinically significant, especially in perioperative and critical care settings.

The mechanism of saline-induced acidosis can be understood using the physicochemical, or Stewart, approach to acid-base balance. In this model, plasma pH depends on three independent variables: the partial pressure of carbon dioxide, the total concentration of weak acids, and the strong ion difference (SID), which is the numerical difference between fully dissociated cations and anions. Under normal physiological conditions, the SID of human plasma averages 38–42 mEq/L. However, the SID of normal saline is essentially zero because it contains equal concentrations of sodium and chloride. Therefore, infusion of saline reduces the plasma SID, leading to an increase in hydrogen ion concentration and a decline in pH, a.k.a. acidosis (2). In contrast, balanced crystalloids, such as Ringer’s lactate or Plasma-Lyte, contain metabolizable anions (lactate, acetate, or gluconate) that serve as buffers and prevent the development of acidosis.

In addition to its effects on acid-base balance, chloride influences kidney and circulatory function. Elevated plasma chloride levels (compared to baseline) cause the afferent arterioles in the kidneys to constrict, decreasing renal blood flow and glomerular filtration. Wilcox first demonstrated this mechanism in human and animal studies, showing that chloride itself (rather than sodium or osmotic factors) drives these changes (3). This reduction in renal perfusion provides a physiological explanation for the risk of kidney injury associated with chloride-rich fluids. Yunos and colleagues later confirmed the clinical importance of this mechanism by finding that adopting a chloride-restrictive fluid strategy in critically ill adults lowered the incidence of acute kidney injury and reduced the need for renal replacement therapy (4).

Clinically, saline-induced acidosis manifests as a gradual decrease in serum bicarbonate concentration, accompanied by a proportional increase in chloride. This condition can develop rapidly following the administration of several liters of saline, especially in patients with limited renal compensatory capacity. Although respiratory alkalosis can offset some of the decrease in pH through hyperventilation, sustained metabolic acidosis can impair myocardial contractility, blunt catecholamine responsiveness, and worsen systemic inflammation. McFarlane and Lee observed that patients who received balanced crystalloids during surgery had more stable hemodynamic and acid-base profiles than patients who received normal saline, which highlights the clinical consequences of fluid selection (5).

Furthermore, the traditional characterization of normal saline as “physiologic” is misleading. Its chloride content (154 mmol/L) substantially exceeds normal plasma levels, creating an ionic environment that is not representative of human plasma. For this reason, many experts now recommend balanced crystalloids as the preferred resuscitation fluid for most clinical situations and reserve normal saline for conditions such as hyponatremia or traumatic brain injury, where hypotonic fluids may be contraindicated.

Acidosis resulting from normal saline administration is a well-characterized and preventable disturbance in acid-base homeostasis. The Stewart framework provides a clear mechanistic basis for understanding this effect, and clinical studies continue to demonstrate its relevance to renal and systemic outcomes. Appropriate fluid choice, guided by physiological principles rather than convention, remains essential to optimizing patient safety and therapeutic efficacy, especially when large volumes of fluid are needed.

References

1. Kellum JA. Saline-induced hyperchloremic metabolic acidosis. Crit Care Med. 2002;30(1):259-261. doi:10.1097/00003246-200201000-00046
2. Morgan TJ. The meaning of acid-base abnormalities in the intensive care unit: part III — effects of fluid administration. Crit Care. 2005;9(2):204-211. doi:10.1186/cc2946
3. Wilcox CS. Regulation of renal blood flow by plasma chloride. J Clin Invest. 1983;71(3):726-735. doi:10.1172/jci110820
4. Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid strategy and kidney injury in critically ill adults. JAMA. 2012;308(15):1566–1572. doi:10.1001/jama.2012.13356
5. McFarlane C, Lee A. A comparison of Plasmalyte 148 and 0.9% saline for intra-operative fluid replacement. Anaesthesia. 1994;49(9):779-781. doi:10.1111/j.1365-2044.1994.tb04450.x