Category: Uncategorized

Given how glaucoma impacts approximately 67 million people in the United States, it is not surprising that glaucoma surgery is one of the most common eye procedures performed today [1]. Despite the frequency with which these procedures occur, anesthesia for glaucoma surgery is not always a straightforward task. Not only do anesthesiologists have a wide range of choices in terms of techniques to use —general, topical, subconjunctival, retrobulbar, peribulbar, and sub-Tenon’s anesthesia are all options— but they also must take steps to avoid serious complications, such as optic nerve damage [2, 3]. This article will discuss some considerations anesthesia providers should keep in mind when preparing for glaucoma surgery. 

Providers often opt for local anesthesia when performing glaucoma surgery [3]. Its advantages include faster discharge and less stress imposed on patients and medical teams, but it may also increase intraocular pressure [4]. The particular application of local anesthesia to be employed depends on several factors. 

When the surgical team opts to perform a nerve block, sub-Tenon’s anesthesia is recommended because it can help avoid placing undue pressure on the optic nerve [2]. Studies have reported that, in many cases, including during longer procedures, sub-Tenon’s techniques result in high patient and surgeon satisfaction [5]. However, a sub-Tenon’s block risks complications such as conjunctival buttonhole, failed surgery because of conjunctival scarring, and potentially globe perforation [3]. Subconjunctival techniques also risk these same complications [3].  

Topical anesthesia, combined with monitored anesthesia care, is an alternative local method that anesthesia providers could use [1]. It is especially effective for trabeculectomy, although in those cases, providers may wish to avoid subconjunctival 2% lidocaine because of its potentially detrimental effects on healing [2]. This technique is also effective for peripheral iridotomy in instances of angle-closure glaucoma and for minimally invasive procedures [2]. A limitation of topical anesthesia, however, is that it may not be appropriate when the procedure is likely to take a long time or the surgeon’s experience is limited [5]. Providers should also note that topical anesthesia demands high levels of patient cooperation [3]. 

Meanwhile, general anesthesia may only be appropriate for some forms of glaucoma surgery. For instance, while providers can opt for general anesthesia for trabeculectomy, they do not typically elect for that technique when performing non-penetrating surgeries, like viscocanalostomy and deep sclerectomy [2]. An advantage of the technique, when it is appropriate, is that it does not necessitate intraoperative patient cooperation [6].  

Unfortunately, general anesthesia also raises concerns for certain classes of patients. For instance, there is an ongoing debate in the medical community about general anesthesia’s potentially neurotoxic effects on the developing brain, causing some practitioners to caution against general anesthesia when operating on children [7]. If a provider elects to use general anesthesia on a child patient, Yeung et al. suggest administering medications like propofol or dexmedetomidine hydrochloride to lessen sevoflurane agitation and delirium and, thus, provide ease of mind to both children and their parents [6].   

All of these considerations make clear the importance of communication when designing an anesthesia regimen for glaucoma surgery. By understanding a patient’s concerns, medical history, medication use, and particular physiology, anesthesia providers will gain a better sense of what type of anesthesia is optimal for glaucoma surgery. 

References 

[1] O. Lodhi and K. Tripathy, “Anesthesia for Eye Surgery,” StatPearls, Updated November 15, 2022. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK572131/.   

[2] A. Pucchio et al., “Anesthesia for ophthalmic surgery: an educational review,” International Ophthalmology, November 2022. [Online]. Available: https://doi.org/10.1007/s10792-022-02564-3.  

[3] O. M. T. Gedar, D. E. Arı, and Ü. Aykan, “Anesthesia Management in Glaucoma Surgery,” ARC Journal of Anesthesiology, vol. 1, no. 3, pp. 9-18, 2016. [Online]. Available: https://doi.org/10.20431/2455-9792.0103002.  

[4] H. Ali et al., “Dexmedetomidine as an Additive to Local Anesthesia for Decreasing Intraocular Pressure in Glaucoma Surgery: A Randomized Trial,” Anesthesiology and Pain Medicine, vol. 10, no. 3, June 2020. [Online]. Available: https://dx.doi.org/10.5812/aapm.100673.  

[5] F. G. Guijarro-Oria et al., “Prospective study of cooperation and satisfaction in glaucoma surgery under sub-Tenon’s anesthesia,” Archivos de la Sociedad Española de Oftalmología (English Edition), vol. 88, no. 3, pp. 102-107, March 2013. [Online]. Available: https://doi.org/10.1016/j.oftale.2012.06.008.   

[6] H. H. Yeung et al., “Perioperative Management of Pediatric Glaucoma Surgery,” International Ophthalmology Clinics, vol. 60, no. 3, pp. 135-140, Summer 2020. [Online]. Available: https://doi.org/10.1097/IIO.0000000000000311.  

[7] T. C. Chang and K. M. Cavuoto, “Anesthesia considerations in pediatric glaucoma management,” Current Opinion in Ophthalmology, vol. 25, no. 2, pp. 118-121, March 2014. [Online]. Available: https://doi.org/10.1097/ICU.0000000000000032.    

Intranasal dexmedetomidine is a sedative agent that has recently gained popularity in pediatric procedural sedation and analgesia. Dexmedetomidine is a highly lipophilic agent, allowing rapid absorption through the nasal mucosa and a rapid onset of action.⁶ This makes intranasal administration an attractive alternative to intravenous administration, mainly when intravenous access is difficult to obtain or maintain, as is often the case for pediatric cases. 

Intranasal dexmedetomidine effectively provides sedation and analgesia for various pediatric procedures, including laceration repair, reduction of fractures and dislocations, and diagnostic imaging studies.¹ It has also shown a favorable safety profile in pediatrics.³ Adverse events are rare and tend to be mild, the most common being agitation or distress upon waking from sedation.¹² Compared to other sedative agents such as midazolam, intranasal dexmedetomidine has been shown to have a more rapid onset of action and a shorter duration of sedation, allowing for a more rapid recovery and discharge from the healthcare facility.⁷ There have been no reported cases of respiratory depression associated with the use of intranasal dexmedetomidine in pediatrics.⁴  

One potential benefit of intranasal dexmedetomidine is the reduced risk of oversedation compared to other sedative agents.⁸ This is thought to be due to the ability of dexmedetomidine to selectively target specific areas of the brain responsible for arousal and sedation, resulting in a more targeted and controllable level of sedation.¹⁴ Additionally, intranasal dexmedetomidine has been associated with a reduced need for rescue medications, such as opioids, to maintain an adequate level of sedation.⁹ This may result in a lower risk of respiratory depression and other adverse events associated with the use of opioids.⁹   

Despite the potential benefits of intranasal dexmedetomidine, there are several considerations to keep in mind when using this agent for pediatric procedural sedation and analgesia. One potential concern is the lack of published data in specific pediatric population subgroups, such as children under six months or those with significant comorbidities.² In these cases, it may be necessary to exercise caution and consider alternative sedative agents. Another consideration is cost, which may be more expensive than other sedative agents.² The sedative’s high cost may restrict its usage in specific healthcare settings or for patients needing adequate insurance coverage.² 

Chronic pain is a significant public health problem, affecting a large portion of the adult population and resulting in significant morbidity and disability.⁵ Intranasal dexmedetomidine can be used as an adjuvant to opioid therapy and has been shown to improve pain control and decrease opioid requirements in adult patients with chronic pain.¹¹ In addition to its use in procedural sedation and analgesia, intranasal dexmedetomidine effectively reduces agitation in adult patients, with a rapid onset of action and a favorable safety profile.^9,12 Agitation can be a challenging and distressing symptom for both patients and healthcare providers.^9,12 

Research has shown this drug to be a safe and effective option for procedural sedation and analgesia in pediatrics and adults.^1,10 Its rapid onset of action, short duration of sedation, and favorable safety profile make it a valuable addition to the sedative armamentarium for practitioners. More research must be done to understand the possible benefits and drawbacks of usage in adults and children, especially in specific subgroups like young children or those with many health problems. 

References 

1. Behrle, N., Birisci, E., Anderson, J., Schroeder, S., & Dalabih, A. (2017). Intranasal Dexmedetomidine as a Sedative for Pediatric Procedural Sedation. The journal of pediatric pharmacology and therapeutics: JPPT : the official journal of PPAG, 22(1), 4–8. https://doi.org/10.5863/1551-6776-22.1.4 

2. Fan, L., Lim, Y., Wong, G. S., & Taylor, R. (2021). Factors affecting successful use of intranasal dexmedetomidine: a cohort study from a national paediatrics tertiary centre. Translational pediatrics, 10(4), 765–772. https://doi.org/10.21037/tp-20-358 

3. Li, L., Zhou, J., Yu, D., Hao, X., Xie, Y., & Zhu, T. (2020). Intranasal dexmedetomidine versus oral chloral hydrate for diagnostic procedures sedation in infants and toddlers: A systematic review and meta-analysis. Medicine, 99(9), e19001. https://doi.org/10.1097/MD.0000000000019001 

4. Gupta, A., Dalvi, N. P., & Tendolkar, B. A. (2017). Comparison between intranasal dexmedetomidine and intranasal midazolam as premedication for brain magnetic resonance imaging in pediatric patients: A prospective randomized double blind trial. Journal of anaesthesiology, clinical pharmacology, 33(2), 236–240. https://doi.org/10.4103/joacp.JOACP_204_16 

5. Mills, S. E. E., Nicolson, K. P., & Smith, B. H. (2019). Chronic pain: a review of its epidemiology and associated factors in population-based studies. British journal of anaesthesia, 123(2), e273–e283. https://doi.org/10.1016/j.bja.2019.03.023  

6. Mohite, V., Baliga, S., Thosar, N., & Rathi, N. (2019). Role of dexmedetomidine in pediatric dental sedation. Journal of dental anesthesia and pain medicine, 19(2), 83–90. https://doi.org/10.17245/jdapm.2019.19.2.83 

7. Panda, S., Pujara, J., Chauhan, A., Varma, A., Venuthurupalli, R., Pandya, H., & Patel, S. (2021). Comparative study of intranasal dexmedetomidine v/s midazolam for sedation of pediatric patients during transthoracic echocardiography. Annals of cardiac anaesthesia, 24(2), 224–229. https://doi.org/10.4103/aca.ACA_17_20 

8. Sado-Filho, J., Corrêa-Faria, P., Viana, K. A., Mendes, F. M., Mason, K. P., Costa, L. R., & Costa, P. S. (2021). Intranasal Dexmedetomidine Compared to a Combination of Intranasal Dexmedetomidine with Ketamine for Sedation of Children Requiring Dental Treatment: A Randomized Clinical Trial. Journal of clinical medicine, 10(13), 2840. https://doi.org/10.3390/jcm10132840 

9. Seppänen, S. M., Kuuskoski, R., Mäkelä, K. T., Saari, T. I., & Uusalo, P. (2021). Intranasal Dexmedetomidine Reduces Postoperative Opioid Requirement in Patients Undergoing Total Knee Arthroplasty Under General Anesthesia. The Journal of arthroplasty, 36(3), 978–985.e1. https://doi.org/10.1016/j.arth.2020.09.032 

10. Shetty, S. K., & Aggarwal, G. (2016). Efficacy of Intranasal Dexmedetomidine for Conscious Sedation in Patients Undergoing Surgical Removal of Impacted Third Molar: A Double-Blind Split Mouth Study. Journal of maxillofacial and oral surgery, 15(4), 512–516. https://doi.org/10.1007/s12663-016-0889-3 

11. Tang, C., & Xia, Z. (2017). Dexmedetomidine in perioperative acute pain management: a non-opioid adjuvant analgesic. Journal of pain research, 10, 1899–1904. https://doi.org/10.2147/JPR.S13938 

12. Uusalo, P., Guillaume, S., Siren, S., Manner, T., Vilo, S., Scheinin, M., & Saari, T. I. (2020). Pharmacokinetics and Sedative Effects of Intranasal Dexmedetomidine in Ambulatory Pediatric Patients. Anesthesia and analgesia, 130(4), 949–957. https://doi.org/10.1213/ANE.0000000000004264 

13. Uusalo, P., Seppänen, S. M., & Järvisalo, M. J. (2021). Feasibility of Intranasal Dexmedetomidine in Treatment of Postoperative Restlessness, Agitation, and Pain in Geriatric Orthopedic Patients. Drugs & aging, 38(5), 441–450. https://doi.org/10.1007/s40266-021-00846-6 

14. Weerink, M. A. S., Struys, M. M. R. F., Hannivoort, L. N., Barends, C. R. M., Absalom, A. R., & Colin, P. (2017). Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clinical pharmacokinetics, 56(8), 893–913. https://doi.org/10.1007/s40262-017-0507-7 

The COVID-19 public health emergency has left a lasting impression on the healthcare industry. Sustained fissures in the infrastructure of the healthcare system are impacting care-seekers, as unprecedented respiratory disease surges overwhelm emergency rooms. The pandemic itself continues to contribute to emerging healthcare problems for Americans, while also highlighting other flaws in the healthcare system. 

Joint Viral Surges Increasing Number of Hospitalizations 

A joint surge in respiratory infections, including RSV, influenza , and COVID-19, have increased the cumulative hospitalization rate to the highest it has been in a decade (1). CDC health data notes 1,600,000 flu illnesses, 13,000 hospitalizations, and 730 deaths (with at least 2 pediatric deaths) from the flu this season (1). Data tracking from the US Department of Health & Human Services offers the conservative estimate that, nationally, 78% of inpatient and 74% of intensive care unit beds are currently in use (2). The healthcare industry will have to reevaluate their inpatient care plans as Americans seek treatment in a flu season with multiple illness cycles. 

Non-investment in Acute Pediatric Care Due to Stretched Budgets 

A study distributed by the American Hospital Association estimates that more than half of hospitals are expected to have negative margins in 2022 relative to a pre-pandemic baseline (3). This suggests billions of dollars lost and an increased strain on the healthcare industry. With supply, labor, and drug expenses rising, the ability for patients to access care in some areas is profoundly impacted by the ability of hospitals to break even as businesses, especially smaller hospitals.  

The recent surge in infections necessitating hospitalization also exposes a lack of acute pediatric care. A growing subset of rural care seekers have to travel to receive specialized attention as “hospital provision of acute care decreased” between 2008 and 2016 (4).  

Nationwide, there is a wave of pediatric units closing. Henrico Doctors’ Hospital in Richmond, VA announced the closure of its pediatric unit to “focus on our care teams’ efforts on the increased demand for adult inpatient medical and surgical care.” Ascension St. John Medical Center in Tulsa, OK shuttered its general pediatric and PICU units to “invest $27M to expand adult ICU capacity”. Hospital costs for providing specialized pediatric care is higher than general care for insured adults (5). The long-standing effects of closures still remain to be seen. However, reports from pediatric physicians alleging that they’ve already reached capacity prior to peak flu season are hinting at the downstream effects of closures.  

Telehealth Capabilities 

Impermanent or a lack of access to telehealth is also emerging as a healthcare problem for Americans. To preempt the amount of people who seek in-person care, many hospitals emphasized telehealth during the COVID-19 pandemic– can this be an effective strategy going forward? A McKinsey study found that virtual care is accessible but reliant upon hospital investment and utilization. Developing a robust telehealth network remains difficult and slow-moving. Policymakers urged the prioritization of virtual visits during the peak of the pandemic and expanded telehealth provisions until 2023. At the end of this period, “absent any changes, most Medicare beneficiaries will lose access to telehealth services unless they live in rural areas or enroll in Medicare Advantage,” and many of those who have been utilizing virtual services will no longer have that option (6). Historic staff shortages still prevent many from receiving timely and consistent virtual appointments. Telehealth may be a path forward, but the industry currently lacks the resources, policy adjustments, and capacity to implement it as standard practice.  

The concurrent surges of the flu, RSV, and COVID expose the underlying problem of reduced hospital capacity, especially for pediatric patients. Tight budgets, the cost of keeping pediatric care units and specialty departments open, staff shortages, and limited telehealth infrastructure are limiting many Americans’ ability to receive care. As America progresses into the new reality of the long-tailed effects of the COVID-19 pandemic, how it handles the emerging healthcare problems exposed by and related to COVID-19 will have large impacts on the health of Americans.  

References 

1. CDC. Weekly U.S. Influenza Surveillance Report. https://www.cdc.gov/flu/weekly/index.htm#ILINet. Updated Nov. 4, 2022.  

2. HHS Protect Public Data Hub. Hospital Utilization. https://public-data-hub-dhhs.hub.arcgis.com/pages/Hospital%20Utilization. Updated Nov. 10, 2022.  

3. Kaufman, Hall & Associates, LLC. The Current State of Hospital Finances: Fall 2022 Update. American Hospital Association September 2022. https://www.aha.org/system/files/media/file/2022/09/The-Current-State-of-Hospital-Finances-Fall-2022-Update-KaufmanHall.pdf 

4. Michelson K, Hudgins J, Lyons T, Monuteaux M, Bachur R, Finkelstein J. Trends in Capability of Hospitals to Provide Definitive Acute Care for Children: 2008 to 2016. Pediatrics January 2020; 145 (1): e20192203. 10.1542/peds.2019-2203. https://publications.aap.org/pediatrics/article/145/1/e20192203/36973/Trends-in-Capability-of-Hospitals-to-Provide 

5. Colvin J, Hall M, Berry J, et al. Financial Loss for Inpatient Care of Medicaid-Insured Children. JAMA Pediatrics. 2016;170(11):1055–1062. doi:10.1001/jamapediatrics.2016.1639. https://jamanetwork.com/journals/jamapediatrics/fullarticle/2551924 

6. Harris J, Bhatnagar S, Newell B, et al. The Future of Telehealth After COVID-19: New Opportunities and Challenges. Bipartisan Policy Center. Oct. 11, 2022. https://bipartisanpolicy.org/download/?file=/wp-content/uploads/2022/09/BPC-The-Future-of-Telehealth-After-COVID-19-October-2022.pdf 

Artificial sweeteners are low- or no-calorie additives often found in sodas and other highly processed foods like yogurt, granola bars, cereal, or microwaveable meals (Bendix, 2022). They are also sold as “tabletop sweeteners” like Splenda and Sweet ‘N Low. Originally, such sweeteners were promoted as healthier replacements for sugar, which has been implicated as a promoter of obesity, diabetes, and other chronic diseases (Rippe, 2016). New research, however, adds to growing concerns that artificial sweeteners may have harmful effects on health. 

In early September, the BMJ published a study in which French researchers identified a potential link between consumption of artificial sweeteners and heart disease (Debras et al., 2022). More than 100,000 French adults participated in the cohort study, which used surveys to assess participants’ dietary intakes and artificial sweetener consumption at different points in time (Debras et al., 2022). The research team defined a “large amount of sweetener” as around 77 milligrams per day, on average (Debras et al., 2022). The study’s results showed that participants who consumed high quantities of aspartame – found in diet soda, yogurt, and cereal – had a higher risk of stroke compared to people who didn’t consume the artificial sweetener (Debras et al., 2022). Similarly, people who consumed large amounts of sucralose – found in Splenda, canned fruit, and ice cream – had a higher risk of coronary heart disease compared to their counterparts (Debras et al., 2022). The study’s findings suggest a potential direct association between higher artificial sweetener consumption (especially aspartame and sucralose) and increased cardiovascular disease risk (Debras et al., 2022). In short, “artificial sweeteners may not be a safe alternative to sugar,” said Mathilde Touvier, the study’s author and a research director at the French National Institute for Health and Medical Research (Bendix, 2022). Previous research has linked artificial sweeteners to other health concerns as well, including diabetes, high blood pressure, obesity, and increased cancer risk (Purohit and Mishra, 2018; Azad et al., 2017; Debras et al., 2022). 

Dr. Katie Page, an associate professor of medicine at the University of Southern California, noted that “the more data that comes out showing these adverse health effects, the less we’re going to want to encourage people to switch from added sugars to non-nutritive sweeteners” (Bendix, 2022). Still, she warned that opting for regular sugar isn’t the healthiest course of action. Instead, Page said that “we really need to encourage people to eat sugar in more moderation and try to decrease sugar consumption” (Bendix, 2022). The World Health Organization (WHO) recommends that adults and children reduce their daily intake of free sugars (such as glucose, fructose, and table sugar found in foods and drinks) to less than 10% of their total energy intake (WHO, 2015). 

Artificial sweeteners are present in tens of thousands of food and drink products worldwide; the global market size was valued around $7.2 billion USD 2021, with a projected annual growth rate of 5% (Market Data Forecast, 2022). The European Food Safety Authority (EFSA), the United States Food and Drug Administration (USFDA), and other health authorities have set guidelines for the daily intake of artificial sweeteners, in addition to existing guidelines for sugar. The recent spate of research highlighting new concerns about the potentially adverse health effects of artificial sweeteners, however, may signal for re-evaluation by relevant health authorities (WHO, 2022). 

References 

Azad, Meghan B., Ahmed M. Abou-Setta, Bhupendrasinh F. Chauhan, Rasheda Rabbani, Justin Lys, Leslie Copstein, Amrinder Mann, et al. “Nonnutritive Sweeteners and Cardiometabolic Health: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies.” CMAJ 189, no. 28 (July 17, 2017): E929–39. https://doi.org/10.1503/cmaj.161390. 

Bendix, Aria. “Spate of New Research Points to the Potential Harms of Artificial Sweeteners.” NBC News, September 8, 2022. https://www.nbcnews.com/health/health-news/artificial-sweeteners-health-risks-heart-disease-blood-sugar-rcna46717. 

Debras, Charlotte, Eloi Chazelas, Bernard Srour, Nathalie Druesne-Pecollo, Younes Esseddik, Fabien Szabo de Edelenyi, Cédric Agaësse, et al. “Artificial Sweeteners and Cancer Risk: Results from the NutriNet-Santé Population-Based Cohort Study.” PLoS Medicine 19, no. 3 (March 2022): e1003950. https://doi.org/10.1371/journal.pmed.1003950. 

Debras, Charlotte, Eloi Chazelas, Laury Sellem, Raphaël Porcher, Nathalie Druesne-Pecollo, Younes Esseddik, Fabien Szabo de Edelenyi, et al. “Artificial Sweeteners and Risk of Cardiovascular Diseases: Results from the Prospective NutriNet-Santé Cohort.” BMJ 378 (September 7, 2022): e071204. https://doi.org/10.1136/bmj-2022-071204. 

Market Data Forecast. “Artificial Sweetener Market Size, Growth, Share | 2022-2027.” Market Data Forecast, January 2022. http://www.marketdataforecast.com/. 

Purohit, Vikas, and Sundeep Mishra. “The Truth about Artificial Sweeteners – Are They Good for Diabetics?” Indian Heart Journal 70, no. 1 (2018): 197–99. https://doi.org/10.1016/j.ihj.2018.01.020. 

Rippe, James M., and Theodore J. Angelopoulos. “Relationship between Added Sugars Consumption and Chronic Disease Risk Factors: Current Understanding.” Nutrients 8, no. 11 (November 4, 2016): 697. https://doi.org/10.3390/nu8110697. 

World Health Organization. “WHO Calls on Countries to Reduce Sugars Intake among Adults and Children.” World Health Organization, March 4, 2015. https://www.who.int/news/item/04-03-2015-who-calls-on-countries-to-reduce-sugars-intake-among-adults-and-children. 

World Health Organization. “Health Effects of the Use of Non-Sugar Sweeteners: A Systematic Review and Meta-Analysis.” Geneva, April 12, 2022. https://www.who.int/publications-detail-redirect/9789240046429.

Nalbuphine is an intravenous medication that is used for analgesia or as an adjuvant to anesthesia [1]. It is often used as an alternative to opioids, owing to its robust analgesic and sedative effects and its avoidance of side effects – including vomiting, nausea, and itching – commonly observed following opioid use [1]. Currently, the FDA permits the use of nalbuphine to address moderate to severe pain that would otherwise demand opioid use, or when other analgesic treatments have failed to assuage pain sufficiently [2]. Beyond these official uses, physicians have administered nalbuphine to treat pains associated with childbirth, surgical abortion, and other significant procedures [2]. 

By activating the kappa opioid receptor, nalbuphine produces analgesia in its recipients [2]. However, nalbuphine is also a partial mu opioid receptor antagonist, which explains its comparatively lower incidence of respiratory depression, nausea, and pruritus than morphine and other opioids [2]. Nalbuphine also exhibits a capping effect, signifying that after surpassing a certain dosage , respiratory depression does not increase further [1]. It is fast-acting: analgesic effects are felt within two to three minutes following intravenous injection, or fifteen minutes after intramuscular or subcutaneous administration [2]. These effects typically persist for three to six hours [2]. 

Several studies have documented the safety and efficacy of nalbuphine compared to other analgesic medications, particularly in novel settings. For instance, Yu et al. conducted a meta-analysis on the efficacy of nalbuphine as an adjuvant to local spinal anesthetics [1]. By aggregating eighteen studies that included a total of 1,633 patients, Yu et al. found that nalbuphine was not significantly more effective than opioids when used as an adjuvant in this context, but did result in fewer occurrences of itching, low blood pressure, and shivering [1]. However, nalbuphine did result in longer-lasting analgesia and 2-segment sensory regression time in comparison to a control group without adjuvant [1]. 

As an adjuvant to spinal anesthesia, nalbuphine appears to be similarly satisfactory in managing labor pain. Sun and colleagues studied the differential effects of sufentanil and nalbuphine when provided as patient-controlled intravenous analgesia (PCIA) [3]. Patients in the nalbuphine group reported higher satisfaction scores, as well as improved pain scores at rest and uterine cramping scores 6, 12, and 24 hours after the surgery [3]. Adverse events and PCIA drug consumption did not differ significantly between the two groups [3]. Ultimately, these results indicate the suitability of nalbuphine in place of sufentanil when treating cesarean-section patients.  

Fang et al. reported similar results in the context of surgical abortions in a 2021 study [4]. While the medications were comparable for multiple metrics, among them hemodynamic fluctuation and intraoperative analgesia, nalbuphine was superior in terms of intensity and incidence of pain following propofol injection, as well as patient satisfaction [4]. 

An interesting question that arises, especially after considering the Sun and Fang studies, is whether nalbuphine operates differently on male and female patients. A recent experiment analyzed the analgesic effects of intravenous nalbuphine on patients undergoing major abdominal surgery [5]. It indicated that female patients exhibit greater levels of analgesia than male patients after taking nalbuphine, which could support administering different dosages based on sex [5]. 

In conclusion, nalbuphine is a powerful medication that can effectively provide pain relief in several contexts. Because of its analgesic efficacy and relative safety compared to medications such as sufentanil, it should be an option considered by anesthetists when administering care. 

References 

[1] P. Yu, J. Zhang, and J. Wang, “Nalbuphine for spinal anesthesia: A systematic review and meta-analysis,” Pain Practice, vol. 22, no. 1, p. 91-106, April 2021. [Online]. Available: https://doi.org/10.1111/papr.13021. 

[2] D. Larsen and C. V. Maani, “Nalbuphine,” StatPearls, Updated May 8, 2022. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK534283/.  

[3] S. Sun et al., “Analgesic Effect Comparison Between Nalbuphine and Sufentanil for Patient-Controlled Intravenous Analgesia After Cesarean Section,” Frontiers in Pharmacology, vol. 11, p. 1-7, November 2020. [Online]. Available: https://doi.org/10.3389/fphar.2020.574493. 

[4] P. Fang et al., “Comparison of Analgesic Effects between Nalbuphine and Sufentanil in First-Trimester Surgical Abortion: A Randomized, Double-Blind, Controlled Trial,” Pain and Therapy, vol. 11, p. 121-132, November 2021. [Online]. Available: https://doi.org/10.1007/s40122-021-00334-0. 

[5] A. E. Ayad et al., “Influences of Gender on Intravenous Nalbuphine Actions After Major Abdominal Surgery: A Multicenter Study,” Pain and Therapy, vol. 10, p. 1215-1233, June 2021. [Online]. Available: https://doi.org/10.1007/s40122-021-00277-6.

The provider-to-patient ratio reflects the number of patients that healthcare providers attend to over the course of an average day. This ratio tends to differ across provider type, whether anesthesiologist, surgeon, or nurse; facility type; and across location – regionally and globally. However, the provider-to-patient ratio, in the OR in particular, has an important impact on the quality of healthcare delivery. 

A number of different factors influence the provider-to-patient ratio across clinical settings. A 2015 U.S.-based study set out to determine provider-to-patient ratios for nurse practitioners and physician assistants working in intensive and acute care units while evaluating factors affecting the ratios. Data revealed that severity of illness, the number of patients, providers, fellows and residents in the unit, a patient’s diagnosis, and the time of day all impacted provider-to-patient ratios ¹.  

A number of actions can be taken to optimize provider-to-patient ratios. Another 2013 intensive care unit-based study yielded data showing that high staff turnover or decreases in quality-of-care indicators in an intensive care unit may be markers of overload, associated with provider-to-patient ratios which are too low. They stressed, in parallel, that telemedicine, advanced healthcare professionals, and non-intensivist medical staff, may help prevent overburdening healthcare providers, though implementation remains an obstacle ².  

In contrast, the provider-to-patient ratio may also be too high and need to be adjusted accordingly. In particular, a recent 2022 study sought to examine the link between different levels of anesthesiologist staffing ratios and the rates of surgical patient morbidity and mortality. The study’s data suggested that increasing overlapping coverage by anesthesiologists results in increased surgical patient morbidity and mortality. In other words, the research team suggested that having anesthesiologists lead the anesthetic management of surgeries that occurred at the same or similar times was detrimental. As such, the potential effects of staffing ratios in perioperative team models should be carefully considered and optimized in order to minimize negative patient outcomes ³. The provider-to-patient ratio could be increased instead by increasing staffing overall. 

A number of methods have been developed to evaluate and reach optimal operating room provider-to-patient ratios. To this end, a new criterion, known as the robust competitive ratio, was recently developed by a group of researchers. Harnessing a robust optimization approach to model the uncertainty in case characteristics and lengths, the team developed an algorithm framework to address staffing and scheduling problems. The algorithms are highly specific, allowing operating room managers to control certain variables unique to their own facility ⁴. 

The World Health Organization (WHO) has stated its vision for a worldwide average ratio of 1 doctor per 1000 people by 2024 – considered optimal to the delivery of efficient and accessible health care. India has been a key country to reach this broad goal – setting the stage for other countries, regions, and institutions to follow suit ⁵.  

In the operating room, provider-to-patient ratios remain a critical aspect of health care delivery. Ongoing research needs to be conducted in order to ensure optimal ratios across clinical settings. Meanwhile, additional research on the factors influencing provider-to-patient ratios, alongside the roles of nurse practitioners and physician assistants, will be key to ensuring the best utilization of providers and optimal patient care outcomes in the operating room and beyond. 

References  

1. Provider to patient ratios for nurse practitioners and physician assistants incritical care units. Am. J. Crit. Care (2015). doi:10.4037/ajcc2015274 

2. Ward, N. S. et al. Intensivist/patient ratios in closed ICUs: A statement from the society of critical care medicine taskforce on ICU staffing. Crit. Care Med. (2013). doi:10.1097/CCM.0b013e3182741478 

3. Burns, M. L. et al. Association of Anesthesiologist Staffing Ratio With Surgical Patient Morbidity and Mortality. JAMA Surg. (2022). doi:10.1001/JAMASURG.2022.2804 

4. Bandi, C. & Gupta, D. Operating room staffing and scheduling. Manuf. Serv. Oper. Manag. (2021). doi:10.1287/msom.2019.0781 

5. Kumar, R. & Pal, R. India achieves WHO recommended doctor population ratio: A call for paradigm shift in public health discourse! J. Fam. Med. Prim. Care (2018). doi:10.4103/jfmpc.jfmpc_218_18 

The Omicron variant of SARS-CoV-2 was first reported to the World Health Organization (WHO) on November 24, 2021, by a viral surveillance organization from South Africa.¹ The earlier subvariants of Omicron, BA.1 and BA.2, were found to be more infectious than previous SARS-CoV-2 variants such as Delta and could infect even those who had received three doses of a COVID-19 vaccine, though vaccination was still instrumental in preventing hospitalization and mortality resulting from infection.^2,3 The genomes of these earlier Omicron subvariants contain more mutations than any of the previous SARS-CoV-2 variants. Most of these mutations are located in the genomic region encoding for the viral spike protein, which the virus uses to bind and enter host cells.⁴  

In April 2022, two new Omicron subvariants were identified by scientists in South Africa. Classified as BA.4 and BA.5, the subvariants are similar to BA.1 and BA.2 but contain additional mutations in the spike protein that may render them even more infectious and resistant to immune responses.⁵ The subvariants are estimated to have emerged in mid-December 2021, while their most recent ancestor originated a month earlier.⁶ Like the earlier Omicron subvariants, BA.4 and BA.5 contain the 69-70del mutation, a six-nucleotide deletion in the viral spike protein gene that results in the deletion of two amino acids. The Thermo Fisher Scientific TaqPath™ SARS-CoV-2 detection kit targets the S gene but fails to do so in the presence of  69-70del, which enables the detection of specific Omicron subvariants like BA.4 and BA.5.⁷ 

Preliminary research has shown that immunity against BA.1 and BA.2 is insufficient in preventing BA.4 and BA.5 infection. An international team of researchers reported that FDA-approved monoclonal antibodies against BA.1 and BA.2 lost their neutralizing activity when tested against BA.4 and BA.5.⁸ The efficacy of antiviral therapeutic drugs such as Remdesivir (which inhibits the viral RNA polymerase) and Nirmatrelvir (inhibits the main viral protease) perform just as well against BA.4 and BA.5 as they do against earlier Omicron subvariants, though the researchers acknowledge that their lack of clinical data prevents them from drawing actionable conclusions (their findings were reported in a “Letter to the Editor,” which is peer-reviewed but not as extensive as a full manuscript). 

A similar study was conducted by Tuekprakhon et al., though they used the serum from people with three SARS-CoV-2 vaccine doses to determine the extent to which vaccine-induced antibodies could neutralize BA.4 and BA.5.⁹ They found that this serum had a 2 to 3-fold reduction in neutralization capability against BA.4 and BA.5 as compared to its capability when measured against BA.1 and BA.2. The implications of such a finding, the authors conclude, is that those with immunity against BA.1 and BA.2 could be infected by the newer Omicron subvariants. 

According to CDC data, BA.4 and BA.5 have rapidly overtaken the earlier subvariants as the most dominant Omicron subvariants currently circulating in the US.¹⁰ In the coming months, more research will emerge on the infectiousness and virulence of these subvariants, but for now, the public and public health experts alike should recognize that the next phase of the COVID-19 pandemic is well underway. 

References 

1. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern. 

2. CDC. Omicron Variant: What You Need to Know. Centers for Disease Control and Prevention https://www.cdc.gov/coronavirus/2019-ncov/variants/omicron-variant.html (2022). 

3. Altarawneh, H. N. et al. Effects of Previous Infection and Vaccination on Symptomatic Omicron Infections. N. Engl. J. Med. 387, 21–34 (2022), DOI: 10.1056/NEJMoa2203965 

4. Khandia, R. et al. Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic. Environ. Res. 209, 112816 (2022), DOI: 10.1016/j.envres.2022.112816 

5. Callaway, E. What Omicron’s BA.4 and BA.5 variants mean for the pandemic. Nature 606, 848–849 (2022), DOI: https://doi.org/10.1038/d41586-022-01730-y 

6. Tegally, H. et al. Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 lineages. (2022), DOI: 10.1101/2022.05.01.22274406. 

7. Frequently asked questions (FAQs) Omicron and Alpha variants: The impact of the 69-70del mutation in the Spike protein of SARS-CoV-2 on TaqPath COVID-19 testing assays, https://assets.thermofisher.com/TFS-Assets/GSD/Reference-Materials/69-70del-s-gene-mutation-eua-faq.pdf 

8. Takashita, E. et al. Efficacy of Antibodies and Antiviral Drugs against Omicron BA.2.12.1, BA.4, and BA.5 Subvariants. N. Engl. J. Med,  (2022), DOI: 10.1056/NEJMc2207519 

9. Tuekprakhon, A. et al. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum. Cell 185, 2422-2433 (2022), DOI: 10.1016/j.cell.2022.06.005 

10. Hassan, A. The Omicron subvariants BA.4 and BA.5 have together become dominant in the U.S., the C.D.C. estimates. The New York Times (2022). 

Around the globe, approximately 230 million surgeries involving general anesthesia occur each year (1). General anesthesia provides the analgesia and unconsciousness required for many surgical procedures. Several different agents can be used for induction (and maintenance) of anesthesia, and despite the ubiquity of general anesthesia in surgeries, anesthesiologists remain divided over the most ideal method of administration: inhalation/mask or intravenous induction? Although previously thought to be equivalent, inhalation and intravenous general anesthetics each demonstrate unique strengths and weaknesses.  

First, inhalation or “volatile” anesthetics — including isoflurane, sevoflurane, desflurane, and nitrous oxide — are a popular choice in the operating room due to their relatively low cost (2-4). Administered through a face mask, tracheal tube, or laryngeal airway, inhalational agents have a rapid onset of action for anesthesia induction, but may provoke complications in pediatric and geriatric patients (4). Although children show less anxiety when anesthesia is induced via mask compared to intravenously, this form of anesthesia appears to be associated with a higher risk of perioperative respiratory distress, especially in patients with extant airway complications (5). Additionally, elderly patients who are maintained on inhalational anesthetics may be more prone to postoperative cognitive dysfunction (6). Finally, although controversial, some evidence points to a cardioprotective effect of inhalational anesthetics — studies show lower levels of cardiac troponin release, an indicator of myocardial damage, in cardiac surgery patients who received inhalational agents compared to those who received intravenous (7, 8).  

Second, intravenous anesthetics — including propofol, the most common, followed by etomidate and thiopental — are considered the more expensive and labor-intensive options, but multiple studies have demonstrated advantages in postoperative outcomes. Compared to inhalational anesthetics, total intravenous anesthesia (TIVA) is associated with significantly fewer incidences of postoperative nausea and vomiting (PONV) (2, 4, 9, 10), with one study finding a relative risk reduction of nearly 40% (9). Evidence also suggests that satisfaction and self-reported recovery scores are higher in patients emerging from TIVA vs. inhalational anesthetics and even in patients induced intravenously then maintained with inhalational agents vs. full inhalation anesthesia (9-12). In contrast to inhalational anesthetics, however, intravenous anesthetics typically control only one function, such as loss of consciousness or analgesia, and cannot provide all aspects of general anesthesia, meaning multiple medications must be administered simultaneously to achieve the same effects as single-agent inhalational anesthetics, adding to the already elevated cost (13).  

In summary, both inhalational and intravenous anesthetics exhibit risks and preventative factors that must be weighed when creating an anesthesia plan for individual patients. Researchers recommend considering the patient’s medical history, type of surgery, drug usage, fear of needles, airway quality, and personal preference (5, 14, 15). Indeed, according to a recent poll, 33% of adult patients preferred intravenous induction for anesthesia, while 50% opted for mask (15); meanwhile, mask induction prevails as the most common anesthesia induction method in pediatric surgery due to vein access issues and fear of propofol infusion syndrome (16). Moreover, although TIVA costs more, the cost of the antiemetic drugs frequently prescribed during emergence from inhalational anesthesia reduces the economic difference between the two methods (4). Both induction methods carry certain risks, but considering holistic perspectives can lead to the development of the safest and most effective regimen for each individual patient.   

References 

1: Weiser, T., Regenbogen, S., Thompson, K., Haynes, A., Lipsitz, S., Berry, W. and Gawande, A. (2008). An estimation of the global volume of surgery: a modeling strategy based on available data. Lancet, vol. 12. DOI: 10.1016/S0140-6736(08)60878-8. 

2: Smith, I. (2003). Inhalation versus intravenous anaesthesia for day surgery. Journal of Ambulatory Surgery, vol. 10. DOI: 10.1016/S0966-6532(02)00045-8. 

3: Rohit, M., Nishant, K. and Aruna, J. (2020). Cost identification analysis of general anesthesia. Journal of Anaesthesiology Clinical Pharmacology, vol. 36. DOI: 10.4103/joacp.JOACP_77_19. 

4: Fleischmann, E., Akca, O., Wallner, T., Arkilic, C., Kurz, A., Hickle, R., Zimpfer, M. and Sessler, D. (1999). Onset time, recovery duration, and drug cost with four different methods of inducing general anesthesia. Anesthesia and Analgesia, vol. 88. DOI: 10.1213/00000539-199904000-00046. 

5: Sommerfield, D. and von Ungern-Sternberg, B. (2019). The mask or the needle? Which induction should we go for? Current Opinion in Anaesthesiology, vol. 32. DOI: 10.1097/ACO.0000000000000729.  

6: Cai, Y., Hu, Haitao, H., Liu, P., Feng, G., Dong, W., Yu, B., Zhu, Y., Song, J. and Zhao, M. (2012). Association between the apolipoprotein E4 and postoperative cognitive dysfunction in elderly patients undergoing intravenous anesthesia and inhalation anesthesia. Anesthesiology, vol. 116. DOI: 10.1097/ALN.0b013e31823da7a2. 

7: Guarracino, F., Landoni, G., Tritapepe, L., Pompei, F., Leoni, A., Aletti, G., Scandroglio, A., Maselli, D., de Luca, M., Marchetti, C., Crescenzi, G. and Zangrillo, A. (2006). Myocardial damage prevented by volatile anesthetics: a multicenter randomized controlled study. Journal of Cardiothoracic and Vascular Anesthesia, vol. 20. DOI: 10.1053/j.jvca.2006.05.012. 

8: de Hert, S., Broecke, P., Mertens, E., van Sommeren, E., de Blier, I., Stockman, B. and Rodrigus, I. (2002). Sevoflurane but not propofol preserves myocardial function in coronary surgery patients. Anesthesiology, vol. 97. DOI: 10.1097/00000542-200207000-00007. 

9: Schraag, S., Pradelli, L., Alsaleh, A., Bellone, M., Ghetti, G., Chung, T., Westphal, M. and Rehberg, S. (2018). Propofol vs. inhalational agents to maintain general anaesthesia in ambulatory and in-patient surgery: a systematic review and meta-analysis. BMC Anesthesiology, vol. 18. DOI: 10.1186/s12871-018-0632-3. 

10: Shui, M., Xue, Z., Miao, X., Wei, C. and Wu, A. (2020). Intravenous versus inhalational maintenance of anesthesia for quality of recovery in adult patients undergoing non-cardiac surgery: a systematic review with meta-analysis and trial sequential analysis. PLoS One, vol. 16. DOI: 10.1371/journal.pone.0254271. 

11: Suzuki, K., Oohata, M. and Mori, N. (2002). Multiple-deep-breath inhalation induction with 5% sevoflurane and 67% nitrous oxide: comparison with intravenous injection of propofol. Journal of Anesthesia, vol. 16. doi.org/10.1007/s005400200001. 

12: Na, S., Jeong, K., Eum, D., Park, J. and Kim, M. (2018). Patient quality of recovery on the day of surgery after propofol total intravenous anesthesia for vitrectomy: A randomized controlled trial. Medicine, vol. 97. DOI: 10.1097/MD.0000000000012699. 

13: Strauss, J. and Giest, J. (2003). Total intravenous anesthesia: on the way to standard practice in pediatrics. The Anesthetist, vol. 52. DOI: 10.1007/s00101-003-0560-5. 

14: Berg, A., Chitty, D., Jones, R. Sohel, M. and Shahen, A. (2005). Intravenous or inhaled induction of anesthesia in adults? An audit of preoperative patient preferences. Anesthesia and Analgesia, vol. 100. DOI: 10.1213/01.ANE.0000150609.82532.C5.  

15: Meltzer, B. (2007). Which is better: IV or gas?: anesthesia providers weigh the merits of intravenous anesthesia vs. using inhalational agents. Association of Perioperative Registered Nurses: Outpatient Surgery. Interview. URL: https://www.aorn.org/outpatient-surgery/articles/outpatient-surgery-magazine/2003/december/which-is-better-iv-or-gas.  

16: Ramgolam, A., Hall, G., Zhang, G., Hegarty, M. and von Ungern-Sternberg, B. (2018). Inhalational versus intravenous induction of anesthesia in children with a high risk of perioperative respiratory adverse events: a randomized controlled trial. Anesthesiology, vol. 128. DOI: 10.1097/ALN.0000000000002152. 

Propofol is an intravenous drug that is widely used for anesthesia and sedation in surgeries and other interventional procedures [1]. It exerts its sedative effects through interacting with GABA_A receptors; at low doses, it increases GABA agonist efficiency and at higher doses it directly opens negative ion channels on GABA receptors and causes hyperpolarization [2]. Propofol is rapidly distributed from blood to tissues and then quickly metabolized in the liver to inactive metabolites (the glucuronide and corresponding quinol glucuronides); this swift process explains why the drug is favored in clinical use – rapid onset and elimination [3]. However, adverse effects can include pain upon injection, hypotension, bradycardia including asystole, and respiratory depression [1,3]. One rare but serious adverse event that has been reported in the literature is propofol neuroexcitation or “propofol frenzy”.   

Propofol is known to have anti-convulsant properties, which are thought to be because of its modulation of the GABA receptor, much like other known anticonvulsive pharmacotherapies [1]. Preclinical studies with rodent hippocampal neurons showed propofol increases the inward current produced by GABA_A receptors. An analysis comparing the EC₅₀ of propofol and GABA infusions reveal both emulsions activate GABA_A receptors in similar ways [4]. Further studies on miniature inhibitory post-synaptic currents (mIPSCs) demonstrated low concentrations of propofol could have inhibitory synaptic effects on neuroexcitation, for example prolonging repetitive opening of GABA_A channels [4,5]. While propofol influences other ion channels such as potassium, sodium, calcium, NMDA, and acetylcholine, its effect on the GABA receptor seems to be strongest, suggesting GABA-mediated neurotransmission is the primary cause of the drug’s neuro-depressive properties [4].   

A landmark study from 2003 found a point mutation in the β3 subunit of the GABA_A receptor was sufficient to extinguish the effects of propofol in causing loss of righting reflex (the analogue for loss of consciousness in mice) [6]. Other studies suggest amino acids in the β1 and β2 subunits are also important for the receptor to interact normally with propofol. An approach involving cysteine residues provided results which suggest propofol’s binding site exists near the middle of the transmembrane domain 3 (TM3) [7].  

However, early clinical studies from the 1990s associated propofol administrations with instances of post-surgical convulsions, perhaps through a drug-induced excitation of the CNS, sometimes called “propofol frenzy” [1,8]. A systematic review found 55 reports of 70 patients without epilepsy, all of whom experienced seizure-like phenomena (SLP) after propofol; for most patients, SLP was observed during either induction of anesthesia (24 patients, 34%) or emergence (28 patients, 40%). Five patients had abnormal EEG, with generalized spiking of neural activity in two and generalized slowing in three [1]. In three patients, abnormal CT results revealed small infarcts and ventricular bleeding, as confirmed by MRI. The review also found 10 reports of 11 patients with epilepsy; their SLP manifested as general tonic-clonic seizures in 82% of patients and opisthotonos in 18%. Case reports such as these have their limitations, predominantly low validity due to selection and observer bias, nonetheless, it should be noted 13 of the 70 patients without epilepsy had no comorbidities and were not concomitantly taking any other medication, yet they too experienced similar intensities of SLP after propofol [1]. 

Propofol also seems to facilitate glutamate release from cerebrocortical glutamatergic terminals, unlike NMDA antagonists such as ketamine and phencyclidine [2]. Neuroexcitation induced by propofol is unique in that there is a lack of a stereotyped pattern in the neocortex. While there is no evidence supporting any pharmacological treatment for propofol neuroexcitation at this time, reducing stimulation and avoiding propofol in subsequent administrations is recommended.  

References 

1. Walder, B., Tramèr, M. R., & Seeck, M. (2002). Seizure-like Phenomena and Propofol: A Systematic Review. Neurology, 58(9), 1327–1332. https://doi.org/10.1212/WNL.58.9.1327  

2. Carvalho, D. Z., Townley, R. A., Burkle, C. M., Rabinstein, A. A., & Wijdicks, E. F. M. (2017). Propofol Frenzy: Clinical Spectrum in 3 Patients. Mayo Clinic Proceedings, 92(11), 1682–1687. https://doi.org/10.1016/j.mayocp.2017.08.022  

3. Adembri, C., Venturi, L., & Pellegrini-Giampietro, D. E. (2007). Neuroprotective Effects of Propofol in Acute Cerebral Injury. CNS Drug Reviews, 13(3), 333–351. https://doi.org/10.1111/j.1527-3458.2007.00015.x  

4. Orser, B. A., Wang, L. Y., Pennefather, P. S., & MacDonald, J. F. (1994). Propofol Modulates Activation and Desensitization of GABA_A Receptors in Cultured Murine Hippocampal Neurons. Journal of Neuroscience, 14(12), 7747–7760. https://doi.org/10.1523/JNEUROSCI.14-12-07747.1994  

5. Takahashi, A., Tokunaga, A., Yamanaka, H., Mashimo, T., Noguchi, K., & Uchida, I. (2006). Two Types of GABAergic Miniature Inhibitory Postsynaptic Currents in Mouse Substantia Gelatinosa Neurons. European Journal of Pharmacology, 553(1–3), 120–128. https://doi.org/10.1016/j.ejphar.2006.09.047  

6. Jurd, R., Arrasa, M., Lambert, S., Drexler, B., Siegwart, R., Crestani, F., Zaugg, M., Vogt, K. E., Ledermann, B., Antkowiak, B., & Rudolph, U. (2003). General Anesthetic actions in vivo Strongly Attenuated by a Point Mutation in the GABA _A Receptor β3 Subunit. The FASEB Journal, 17(2), 250–252. https://doi.org/10.1096/fj.02-0611fje  

7. Yip, G. M. S., Chen, Z.-W., Edge, C. J., Smith, E. H., Dickinson, R., Hohenester, E., Townsend, R. R., Fuchs, K., Sieghart, W., Evers, A. S., & Franks, N. P. (2013). A propofol Binding Site on Mammalian GABA_A Receptors Identified by Photolabeling. Nature Chemical Biology, 9(11), 715–720. https://doi.org/10.1038/nchembio.1340  

8. Collier, C., & Kelly, K. (1991). Propofol and Convulsions—The Evidence Mounts. Anesthesia and Intensive Care, 19(4), 573–575. https://doi.org/10.1177/0310057X9101900416 

Aspirin is commonly used to reduce fever and/or relieve mild to moderate pain, such as from headaches, menstrual cramps, arthritis, and muscle aches, similar to other non-steroidal anti-inflammatory drugs (NSAIDs). However, it also has significant anti-platelet properties, leading to its use by many people to prevent heart attack or ischemic stroke, which are caused by a clot blocking blood flow to part of the heart and brain respectively (MedlinePlus, Mayo Clinic). Based on available data, leading medical organizations established guidelines for what populations would benefit from daily low-dose aspirin for heart attack prevention. Recent research has led to more conservative guidelines for older adults, due to a growing recognition and cautiousness of the increased bleeding risk associated with aspirin (Mayo Clinic, Zheng & Roddick). 

A physician may recommend aspirin for prevention purposes for adults aged 40 to 59 who are considered to be at high risk of experiencing a heart attack (or ischemic stroke). Risk factors include a prior heart attack, stroke, or mini-stroke, a stent, coronary bypass surgery, and angina (MedlinePlus, Mayo Clinic). However, the anticoagulant effect occurs systemically, leading to increased bleeding in cases of injury, as well as an increased risk of spontaneous bleeding (Mayo Clinic). A large meta-analysis that included data from over 160,000 patients concluded that “the use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding” (Zheng & Roddick). This risk outweighs the benefit for many older adults. As a result, some guidelines caution that those age 60 or older without cardiovascular disease should not participate in a daily regimen of aspirin for heart attack prevention. Other guidelines continue to have a threshold of 70 years – those aged 60 to 69 should discuss the benefits and potential harms of aspirin with their physician (Mayo Clinic). 

Aspirin, also known as acetylsalicylic acid, interferes with normal clotting processes in blood. It and other NSAIDs inhibit cyclooxygenase (COX), an enzyme that leads to the production of prostaglandins, which are involved in inflammation, pain, swelling, and fever. COX is also involved in other processes, the disruption of which leads to the side effects associated with aspirin, such as gastric irritation. Though researchers aim to develop better anti-inflammatory medication that selectively targets COX-2 rather than affecting both COX-1 and COX-2 to reduce adverse gastrointestinal effects, studies show that COX-2 inhibitors may increase the risk of clots. As a result, aspirin, which is a nonselective COX inhibitor, remains important for heart attack prevention (Vane & Botting). 

As with all medication, people who take aspirin regularly must be careful not to take other drugs with interfering or compounding effects unless directed to by their physician. Such medications include anticoagulants, ACE inhibitors, beta blockers, diuretics, corticosteroids, and some antidepressants. Ibuprofen also generally should not be taken concurrently (MedlinePlus, Mayo Clinic). In addition, some herbal and dietary supplements may increase bleeding risk when taken alongside aspirin. Due to the anticoagulant properties of the drug, it is also important that surgeons are aware of patient’s ongoing aspirin therapy to preempt dangerous bleeding during surgery (Mayo Clinic). 

Current data demonstrates the benefit of aspirin as a heart attack prevention method in a select, high risk population. However, studies also highlight the potential harms of the medication. Individuals should always seek the advice of their healthcare provider before starting or stopping an aspirin regimen. Additional research will continue to improve the resources available for reducing the risk of ischemic events. 

References 

Mayo Clinic Staff. Daily aspirin therapy: Understand the benefits and risks. Mayo Clinic. October 15, 2021. Available: https://www.mayoclinic.org/diseases-conditions/heart-disease/in-depth/daily-aspirin-therapy/art-20046797 

MedlinePlus. Aspirin. Updated May 15, 2021. Available: https://medlineplus.gov/druginfo/meds/a682878.html 

Vane, J. R. & Botting, R. M. The mechanism of action of aspirin. Thrombosis Research. 2003;110(5-6):255-8. doi: 10.1016/s0049-3848(03)00379-7. 

Zheng, S. L. & Roddick, A. J. Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events. JAMA. 2019;321(3):277-287. doi:10.1001/jama.2018.20578.