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Surgery in the prone position, or lying face down, as opposed to supine where the patient is lying on their back with their face up, is used when a surgery requires access to anatomical structures posteriorly. This can include access to the posterior head, neck, or spine during a spinal surgery or even for access to the upper urinary tracts during urological surgeries [1].

Prone surgery is associated with many complications that often stem from the prolonged and increased pressure on anterior organs. Increased abdominal pressure causes excess pressure to build on the inferior vena cava, the major vein which returns blood from the body back to the heart. This results in a back-up of blood in the body and thus, less blood returning to the heart. Further, the pressure on the chest wall leads to decreased output from the heart which results in a subsequent drop in blood pressure. This drop in blood pressure can be dangerous in the setting of surgery. Additionally, respiratory rate is affected in prone surgery, which can lead to further decreases in cardiac output and oxygenation [2]. Some of the potential cardiovascular complications of prone surgery include hypovolemia and cardiac arrest [1]. Increased bleeding is also a common complication of the prone position, especially in spinal surgery, as damage to engorged veins can cause greater bleeding than damage to normal veins [2].

Prone positioning can also increase intraocular pressure [3]. Malpositioning of the patient can lead to direct pressure on the eye for an extended period, which can lead to irreversible visual loss. While postoperative vision loss is commonly described in journals, the true rate of incidence remains low [1]. However, while rare, it is necessary for both surgeons and anesthesiologists to watch for adequate patient eye protection during prone surgeries to avoid this potentially devastating complication.  

There are many preoperative risk factors that play a role in postoperative complications of prone surgery. In terms of postoperative vision loss, older patients who have an elevated intraocular pressure at baseline typically are at higher risk for vision loss [3]. Hypertension, diabetes, obesity, anemia, atherosclerosis, and history of smoking are all risk factors for postoperative complications [5].

Ideally in a prone surgery, positioning will maximize ventilation of the patient while minimizing risk of bleeding and damage to vital organs [2]. Over the years, special operating tables and other devices such as chest rolls and bolsters have been designed to promote ideal prone positioning, decrease pressure on the abdomen and chest, and lower complications associated with prone positioning. Further, careful positioning can prevent vision loss by changing the degree of the bed so that the head is above the heart. This allows for less venous pooling of blood in the eye and orbit which can help to decrease intraocular pressures [4]. Reducing the length of time patients are in prone positioning can also help to decrease complications. Surgeries that are longer than 6.5 hours are considered prolonged, and it may be beneficial to use a series of shorter surgeries to reduce risks of complications. On the other hand, risks of multiple surgeries may outweigh the risks of one prolonged prone surgery [3,5]. Overall, for preventing complications of prone surgery, it is important to monitor fluids, using IV fluids when necessary to replace intravascular volume, monitor blood loss and hemoglobin level, and optimize blood pressure within 20-25% of baseline blood pressure [5,6].  

References 

1. Kwee, Melissa M., et al. “The Prone Position during Surgery and Its Complications: A Systematic Review and Evidence-Based Guidelines.” International Surgery, vol. 100, no. 2, Feb. 2015, pp. 292–303, www.ncbi.nlm.nih.gov/pmc/articles/PMC4337445/, 10.9738/intsurg-d-13-00256.1. 

2. Schonauer, Claudio, et al. “Positioning on Surgical Table.” European Spine Journal, vol. 13, no. S01, 22 June 2004, pp. S50–S55, 10.1007/s00586-004-0728-y. 

3. ‌van Wicklin, Sharon Ann. “Systematic Review and Meta-Analysis of Prone Position on Intraocular Pressure in Adults Undergoing Surgery.” International Journal of Spine Surgery, 14 Apr. 2020, p. 7029, 10.14444/7029. 

4. Ozcan, Mehmet S., et al. “The Effect of Body Inclination during Prone Positioning on Intraocular Pressure in Awake Volunteers: A Comparison of Two Operating Tables.” Anesthesia & Analgesia, vol. 99, no. 4, Oct. 2004, pp. 1152–1158, 10.1213/01.ane.0000130851.37039.50.  

5. ‌Shifa, Jemal, et al. “A Case of Bilateral Visual Loss after Spinal Cord Surgery.” Pan African Medical Journal, vol. 23, 2016, 10.11604/pamj.2016.23.119.8443.  

6. Lee, Lorri A., et al. “The American Society of Anesthesiologists Postoperative Visual Loss Registry.” Anesthesiology, vol. 105, no. 4, 1 Oct. 2006, pp. 652–659, 10.1097/00000542-200610000-00007.  

The Telehealth Modernization Act was passed in 2022, modifying requirements for the coverage of telehealth services under Medicare. It effectively extends certain flexibilities initially authorized during the COVID-19 public health emergency. Endorsed by a number of professional organizations, from the American Association of Orthopedic Surgeons (AAOS) (1) to the American Hospital Association (AHA) (2), the legislation has a number of critical implications.

In April 2020, at the beginning of the pandemic, over 40% of Medicare fee-for-service primary care visits were carried out through telehealth, and over 10 million beneficiaries accessed telehealth services from mid-March through early July of 2020 (3). While regulatory coverage restrictions have long prevented telehealth services for many of the nation’s roughly 61 million Medicare beneficiaries, the COVID-19 pandemic acutely highlighted the importance of access to telehealth care.

Among other elements, the bill allows (1) federally qualified health centers and rural health clinics to act as the location of the health care practitioner; (2) the home of a beneficiary to act as the location of the health care beneficiary for all services; and (3) all types of practitioners to provide telehealth services, as assessed by the Centers for Medicare and Medicaid Services (4).  

The Telehealth Modernization Act applies to a full spectrum of health care. In addition to providing Medicare recipients many additional telehealth services, the act will 1) help patients continue to access telehealth from varied health care workers, from speech language pathologists to physical therapists, and 2) help Medicare patients receiving services ranging from home dialysis to hospice care keep receiving this care through telehealth. 

The most important implication of the Telehealth Modernization Act is the increased flexibility of – and therefore access to – health care. Permanently eradicating geographic and originating site restrictions, the Telehealth Modernization Act will reduce access barriers that have continuously increased in recent times. Relatedly, it will enable greater access to high-quality health care services for vulnerable populations, in particular among seniors.  

In addition to ensuring access to essential care for patients, the increased use of telehealth helps address certain workforce pressures, including those that arose as a result of an overwhelmed healthcare system during the COVID-19 pandemic.  

Many opportunities and challenges remain to be addressed in view of a telehealth-centric future, however (5). First, patient trust and security are top priorities (6). One study found that ensuring that health services provision meets patients’ needs at all times depends not only on a certain degree of flexibility in care delivery modalities and interprofessional collaboration, but also healthy, sustained relationships with patients. Second, and relatedly, it will be important to ensure that patients receive the right amount of empathic, personalized care, crucial to a good patient experience and patient well-being. As many have experienced, virtual interactions so far have major differences compared to in-person ones. To this end, guidelines and training are needed, as well as careful attention to technological challenges and interpersonal relationship needs (7).  

Overall, telehealth has been beneficial for millions of Americans, especially during the pandemic (3). While continued research is required to ensure that its key provisions are implemented in the most smooth and efficient way possible, the Telehealth Modernization Act will surely continue to positively reshape healthcare delivery.  

References 

1. AAOS’ Advocacy Efforts Focus on Access to Quality Care [Internet]. [cited 2022 Jul 25]. Available from: https://www.aaos.org/aaosnow/2022/may/advocacy/advocacy01/ 

2. AHA Comments to Modernization Subcommittee of the Healthy Future Task Force Re: Telehealth | AHA [Internet]. [cited 2022 Jul 25]. Available from: https://www.aha.org/lettercomment/2022-03-04-aha-comments-modernization-subcommittee-healthy-future-task-force-3-4-22 

3. Scott, Schatz, Shaheen Introduce Bipartisan Legislation to Increase Access to Telehealth in the Midst of the Pandemic | U.S. Senator Tim Scott of South Carolina [Internet]. [cited 2022 Jul 25]. Available from: https://www.scott.senate.gov/media-center/press-releases/scott-schatz-shaheen-introduce-bipartisan-legislation-to-increase-access-to-telehealth-in-the-midst-of-the-pandemic 

4. H.R.1332 – 117th Congress (2021-2022): Telehealth Modernization Act | Congress.gov | Library of Congress [Internet]. [cited 2022 Jul 25]. Available from: https://www.congress.gov/bill/117th-congress/house-bill/1332 

5. Blandford A, Wesson J, Amalberti R, AlHazme R, Allwihan R. Opportunities and challenges for telehealth within, and beyond, a pandemic. The Lancet Global Health. 2020. doi: 10.1016/S2214-109X(20)30362-4. 

6. Hale TM, Kvedar JC. Privacy and security concerns in telehealth. Virtual Mentor. 2014. doi: 10.1001/virtualmentor.2014.16.12.jdsc1-1412. 

7. Breton M, Sullivan EE, Deville-Stoetzel N, McKinstry D, DePuccio M, Sriharan A, et al. Telehealth challenges during COVID-19 as reported by primary healthcare physicians in Quebec and Massachusetts. BMC Fam Pract. 2021; doi: 10.1186/s12875-021-01543-4. 

Viral shedding refers to the expulsion of live virus from an organism in which the virus has successfully replicated.¹ Shedding can occur via several different mechanisms, such as budding, whereby viral particles exit the host cell membrane by surrounding themselves with molecules from the membrane, and apoptosis, whereby viral particles force cells to undergo cell death and can then be released into the extracellular space.² The amount of viral shedding by infected individuals depends on the virus in question, the stage of infection, and the host’s immunity against the virus, including if they have been vaccinated.

 Vaccination can protect individuals from viral infection such that even upon exposure to a virus, the individual’s vaccine-induced immunity kills the infectious agent before it can replicate and cause illness. In reality, breakthrough infections can also occur, in which vaccinated individuals contract a viral illness. Vaccinated individuals who contract breakthrough infections may nevertheless have better outcomes than unvaccinated individuals who become infected. Variants of SARS-CoV-2, such as the Delta variant, have caused breakthrough infections, but it has been found that people vaccinated against COVID-19 are much less likely than unvaccinated individuals to develop severe symptoms.³ 

Does this mean that fully vaccinated individuals are also less likely to transmit the virus to others – do they shed less virus? Dr. Jiwon Jung and other South Korean researchers recently published their findings on this very question. In a recent Journal of the American Medical Association paper, Jung et al. reported on their study of the transmissibility of COVID-19 according to vaccination status.⁴ The study involved two cohorts of vaccinated and unvaccinated individuals. The first cohort was subject to a secondary transmission study: the contacts of the cohort members were tracked, and their COVID-19 infections were recorded. The second cohort underwent a viral kinetics shedding study: patients submitted saliva samples each day of the study, and the viral load in the samples was measured using polymerase chain reaction (PCR). 

The results from both cohorts indicate that vaccinated individuals with breakthrough infections shed less virus than unvaccinated infected patients. The risk of secondary transmission was significantly lower in the breakthrough group than in the non-breakthrough group. Additionally, while patients in the breakthrough and non-breakthrough had a similar initial viral load after infection, fully vaccinated patients had a shorter duration of viral shedding compared to partially vaccinated and unvaccinated individuals. 

Though convincing, the study, as its authors acknowledge, has several limitations. Perhaps most significantly, viral shedding was only measured by the amount of virus in saliva samples. Due to “logistical challenges,” nasopharyngeal swab samples were not used, though they could have enabled more accurate data on viral shedding, especially given the incomplete data regarding the amount of viral shedding at different body sites over the course of infection.⁵ Furthermore, the study only tracked nosocomial secondary transmission – that is, infections originating in a hospital – which may bias the results. Finally, the cohort 1 study began before the emergence of the infectious Delta variant but concluded after it was widespread. The study did not control for SARS-CoV-2 variant, and the conclusions drawn from it are therefore limited. Nevertheless, this important study hopefully paves the way for future research into viral shedding in vaccinated individuals. 

References 

1. Yan, D. et al. Characteristics of Viral Shedding Time in SARS-CoV-2 Infections: A Systematic Review and Meta-Analysis. Front. Public Health 9, (2021), DOI: 10.3389/fpubh.2021.652842 

2. Badu, K. et al. SARS-CoV-2 Viral Shedding and Transmission Dynamics: Implications of WHO COVID-19 Discharge Guidelines. Front. Med. 8, (2021), DOI: 10.3389/fmed.2021.648660 

3. CDC. COVID-19 Vaccination. Centers for Disease Control and Prevention https://www.cdc.gov/coronavirus/2019-ncov/vaccines/effectiveness/why-measure-effectiveness/breakthrough-cases.html (2020). 

4. Jung, J. et al. Transmission and Infectious SARS-CoV-2 Shedding Kinetics in Vaccinated and Unvaccinated Individuals. JAMA Netw. Open 5, e2213606 (2022), DOI:10.1001/jamanetworkopen.2022.13606 

5. Congrave-Wilson, Z. et al. Change in Saliva RT-PCR Sensitivity Over the Course of SARS-CoV-2 Infection. JAMA 326, 1065–1067 (2021), DOI: 10.1001/jama.2021.13967 

While nerve blocks are widely used alongside anesthesia, its effect may last only up to a few hours, and increasing the dose to prolong the block may result in adverse side effects on the cardiovascular or central nervous systems ¹. Therefore, an adjuvant to anesthetics is often used because of its synergistic effect with anesthetics, prolonging the duration of sensory-motor blocks and limiting the dose requirement of local anesthetics. Over time, local anesthetics of choice have evolved from classical opioids to a number of drugs with varying mechanisms of action ². Epinephrine, opioids, alpha-2 adrenergic antagonists, steroids, anti-inflammatory drugs, midazolam, and ketamine, among others, have been used to augment the effect of local anesthetics. Among these, epinephrine has been commonly used as an adjuvant to anesthetics for a few reasons. 

One of the oldest additives to local anesthetic solutions, epinephrine potentiates local anesthetics through its anti-nociceptive properties mediated by alpha-2 adrenoreceptor activation ³, alongside its vasoconstrictive properties which limit the systemic reabsorption of local anesthetics and thus prolong anesthetic action ⁴. It has a recommended dosing of 0.5-1.0 μg/kg ⁵. 

One study found that using lidocaine with high-dose epinephrine (200 μg/mL) for an axillary block prolonged motor block and sensory block by approximately 25-40 minutes but increased the incidence of tachycardia and hypertension. A lower dose of 25 μg/mL, however, had a minimal effect, prolonging a motor block by only 10 minutes and a sensory block by just 30 minutes ⁶. Another study found that, when added alongside mepivacaine for a brachial plexus block, epinephrine prolonged a motor and sensory block by approximately one hour ⁷. However, epinephrine has not been found to prolong blockade with ropivacaine and does not match up to other adjuvants, such as clonidine, in the prolongation of a brachial plexus block with bupivacaine ^8,9.  

In addition, as an adjuvant, epinephrine can be added to local anesthetics to detect intravascular injection. As such, it has played a significant role in preventing the inadvertent intravascular administration of local anesthetic solutions. However, the recent surge in the routine use of ultrasonography in nerve blocks has decreased its utility in these contexts.  

A few limitations on the use of epinephrine as an adjuvant to anesthetics remain. Not only may perineural administration of epinephrine incur detrimental effects to the nerves of patients who are smokers or who suffer from diabetes mellitus or hypertension ¹⁰, but also epinephrine in too high a dose may be neurotoxic.  

A lower dose of epinephrine might be just as effective at prolonging its anesthetic effects while limiting the hazards associated with its unintentional intravascular injection. To this end, one study concluded that 1.25 μg/mL of epinephrine, when coinjected with clinical doses of bupivacaine and levobupivacaine, resulted in a comparable vasoconstrictor effect in human skin to that of higher concentrations ¹¹.  

Further research is warranted to investigate how to address ongoing challenges linked to the use of epinephrine as an adjuvant to anesthetics. In this context, research will particularly need to focus on minimizing its deleterious effects.  

References 

1. Jeon, Y. H. The use of adjuvants to local anesthetics: Benefit and risk. Korean Journal of Pain (2018). DOI: 10.3344/kjp.2018.31.4.233

2. Swain, A., Nag, D. S., Sahu, S. & Samaddar, D. P. Adjuvants to local anesthetics: Current understanding and future trends. World J. Clin. Cases (2017). DOI: 10.12998/wjcc.v5.i8.307

3. Collins, J. G., Kitahata, L. M., Matsumoto, M., Homma, E. & Suzukawa, M. Spinally administered epinephrine suppresses noxiously evoked activity of WDR neurons in the dorsal horn of the spinal cord. Anesthesiology (1984). DOI: 10.1097/00000542-198404000-00001

4. Cazaubon, Y. et al. Population pharmacokinetics of articaine with 1:200,000 epinephrine during third molar surgery and simulation of high-dose regimens. Eur. J. Pharm. Sci. (2018). DOI: 10.1016/j.ejps.2017.11.027

5. Jöhr, M. & Berger, T. M. Caudal blocks. Paediatric Anaesthesia (2012). DOI: 10.1111/j.1460-9592.2011.03669.x

6. Dogru, K. et al. Hemodynamic and blockade effects of high/low epinephrine doses during axillary brachial plexus blockade with lidocaine 1.5%: A randomized, double-blinded study. Reg. Anesth. Pain Med. (2003). DOI: 10.1016/S1098-7339(03)00225-6

7. Song, J. H. et al. Comparison of dexmedetomidine and epinephrine as an adjuvant to 1% mepivacaine in brachial plexus block. Korean J. Anesthesiol. (2014). DOI: 10.4097/kjae.2014.66.4.283

8. Weber, A., Fournier, R., Van Gessel, E., Riand, N. & Gamulin, Z. Epinephrine does not prolong the analgesia of 20 mL ropivacaine 0.5% or 0.2% in a Femoral three-in-one block. Anesth. Analg. (2001). DOI: 10.1097/00000539-200111000-00060

9. Eledjam, J. J. et al. Brachial plexus block with bupivacaine: effects of added alpha-adrenergic agonists: comparison between clonidine and epinephrine. Can. J. Anaesth. (1991). DOI: 10.1007/BF03036962

10. Myers, R. R. & Heckman, H. M. Effects of local anesthesia on nerve blood flow: Studies using lidocaine with and without epinephrine. Anesthesiology (1989). DOI: 10.1097/00000542-198911000-00021

11. Newton, D. J., McLeod, G. A., Khan, F. & Belch, J. J. F. The effect of adjuvant epinephrine concentration on the vasoactivity of the local anesthetics bupivacaine and levobupivacaine in human skin. Reg. Anesth. Pain Med. (2004). DOI: 10.1016/j.rapm.2004.04.011

Medical licenses are a key regulatory measure which determines who can (and can’t) practice medicine. A medical license can only be obtained once certain basic requirements have been met, including a doctorate from an accredited U.S. or international medical school, a certificate of completion of residency, a passing score on the licensing examination, and demonstration of mental, moral, and physical fitness to practice medicine. Many licensing boards even limit the number of attempts that can be made to pass the licensing examinations, known as USMLE for medical doctorate candidates or COMLEX-USA for osteopathic doctorate candidates [1]. These steps alone take years to complete and thus regulations leave only a select few who qualify as candidates for a license.

Yet even once obtained, medical licenses are highly regulated when it comes to where and how they can be used. Medical licenses are administered by individual states, not the federal government. As such, the regulations around obtaining and maintaining a medical license is different throughout different U.S. states. Examples of key variances include the minimum number of years of postgraduate residency, or the number of times one is allowed to retake the licensing examination. Because of the variance in qualifications between states, doctors in the U.S. are often geographically limited to their primary state of practice. However, increased mobility of physicians and prevalence of telehealth services have led to a rise in doctor-patient relationships across state borders. Minute differences in license regulations can therefore pose a large obstacle when it comes to access to care.  

In light of this, some states have implemented medical license reciprocity, which allows for expedited licensure to practice in another state. Essentially, these states have agreed to coordinate the necessary requirements to receive and maintain a medical license, therefore enabling physicians who participate in the Interstate Medical Licensure Compact to more easily practice across state lines. As of August 2021, 32 states/territories were participating in medical license reciprocity [2], including: 

Alabama, Arizona, Colorado, Delaware, Georgia, Guam, Idaho, Illinois, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Michigan, Minnesota, Mississippi, Montana, Nebraska, Nevada, New Hampshire, North Dakota, South Dakota, Oklahoma, Texas, Tennessee, Utah, Vermont, West Virginia, Wisconsin, Wyoming, and Washington 

Several more have passed the IMLC but are currently in the process of implementation or are experiencing implementation delays.  

Just as medical licenses must be earned differently in different states, the grounds for license revocation varies by state. However, in this regard there are more similarities than differences. Doctors may lose their license if they demonstrate they no longer have the mental, physical, or moral capacity to practice safely. For example, some causes of license revocation in California are substance abuse, insurance fraud, patient abuse, violating drug prescription laws, loss of records/violation of HIPAA, and discrimination [3].

Given the surge in popularity of telehealth appointments resulting from the COVID-19 pandemic, patients have new expectations concerning the availability of their most trusted physicians, even if that means that the online appointment must take place across state lines. As a result, it is likely that more states will look to join the Interstate Medical Licensure Compact in the years to come. 

References 

1. About physician licensure. FSMB. (n.d.). Retrieved from https://www.fsmb.org/u.s.-medical-regulatory-trends-and-actions/guide-to-medical-regulation-in-the-united-states/about-physician-licensure/#:~:text=All%20state%20medical%20boards%20require,training%20to%20obtain%20a%20license.  

2. Compact State Map. Interstate Medical Licensure Compact. (2021, August 20). Retrieved from https://www.imlcc.org/participating-states/  

3. California, S. of. (2022.). Laws. Medical Board of California. Retrieved from https://www.mbc.ca.gov/About/Laws/California-Law/  

Post-operative cognitive dysfunction (POCD) is an expansive definition for the wide spectrum of cognitive deficits seen in patients after anesthesia and surgery. Most common deficits of POCD include cognitive impairments, such as memory and information processing, which can also be present in the aftermath of anesthetics. Current data suggests that POCD is most directly caused by neuroinflammation and microglial activation, which triggers an immuno-hormonal cascade increasing the permeability of the blood-brain barrier, ultimately promoting the influx of macrophages into the brain parenchyma. The pro-inflammatory cytokines synthesized by these macrophages cause neuronal damage, apoptosis, and impaired neurotransmission to the hippocampus, medial prefrontal cortex, amygdala, and the cingulate cortex, brain regions critical in memory, reward, emotion, and judgement [1-3].  

Eckenhoff et. al.’s research in 2004 demonstrated clinically relevant concentrations of inhaled anesthetics such as halothane and isoflurane could induce the oligomerization of amyloid β (peptides that compose the amyloid plaques in Alzheimer’s patients) and amyloid-β-induced cytotoxicity [4]. However, intravenous anesthetics such as ethanol and propofol did not have this effect. While desflurane (another inhalational agent) alone does not induce caspase-3 activation or affect amyloid precursor protein cells, a combination of desflurane and hypoxia does both [5]. Additionally, abnormal tau tangles are one of the hallmarks of AD. In 2007, a murine study found anesthetics including chloral hydrate, pentobarbital and isoflurane produced rapid and massive tau protein hyperphosphorylation and inhibition of Ser/Thr phosphatase (PP) activity. These researchers confirmed PP2A (a subtype of PPs) is the main phosphatase driving tau dephosphorylation; their inhibition is a direct result of hypothermia induced by anesthesia [6,7]. Another preclinical study found the inhaled anesthetic sevoflurane generated behavioral deficits in spatial learning and memory in aged rats; the rats also experienced hippocampal alterations, most notably a downregulation of the cAMP/CREB signaling pathway, a pathway extensively implicated as a “hot spot” of long-term potentiation, memory, and neuroprotection [8].  

Following the use of intravenous agents, specific neurological and behavioral changes have been reported. A prolonged infusion of propofol significantly impaired spatial learning in mice, as measured by the Morris water maze behavioral assessment. The CA1 region of the hippocampus showed significant autophagy inhibition, leading to the observed cognitive deficits [9]. Autophagy is the fundamental catabolic process involving degradation of dysfunctional cellular molecules to supply energy and compounds for further biosynthesis. Defective autophagy is associated with increased aging as well as diseases like cancer or neurodegenerative and muscular disorders [10]. Inhaled anesthetics also affect this process, as sevoflurane may cause impaired memory performance and increase hippocampal neuronal apoptosis through its suppression of autophagic processes, potentially increasing the risk of POCD [11]. However, rapamycin, an immunosuppressive drug, reduced the cognitive effects of sevoflurane by inducing autophagy [9,11].

POCD in human patients is often thought to be induced by increased activity of GABA_A receptors, which most general anesthetics act on. The subtypes of GABA_A receptors may be responsible for the different effects of general anesthesia, such as amnesia, sedation, and hypnosis [13]. Preclinical investigations have pinpointed the alpha-5 subunit of GABA_A receptors to be especially responsible, given their significant upregulation after administration of GABAergic anesthetics [12]. Sevoflurane may damage synaptic plasticity by decreasing postsynaptic density protein in mPFC, highlighting another potential mechanism ultimately generating POCD [14].

Although research has proposed plausible mechanisms by which general anesthetics may lead to POCD, interesting perspectives for future consideration involve in-depth study of predisposing and precipitating factors of POCD.

References 

1. Wang, B., Li, S., Cao, X., Dou, X., Li, J., Wang, L., Wang, M., & Bi, Y. (2017). Blood-brain barrier disruption leads to postoperative cognitive dysfunction. Current Neurovascular Research, 14(4), 359–367. https://doi.org/10.2174/1567202614666171009105825 

2. Vacas, S., Degos, V., Feng, X., & Maze, M. (2013). The neuroinflammatory response of postoperative cognitive decline. British Medical Bulletin, 106, 161–178. https://doi.org/10.1093/bmb/ldt006  

3. Cascella, M., & Bimonte, S. (2017). The role of general anesthetics and the mechanisms of hippocampal and extra-hippocampal dysfunctions in the genesis of postoperative cognitive dysfunction. Neural Regeneration Research, 12(11), 1780–1785. https://doi.org/10.4103/1673-5374.219032  

4. Eckenhoff, R. G., Johansson, J. S., Wei, H., Carnini, A., Kang, B., Wei, W., Pidikiti, R., Keller, J. M., & Eckenhoff, M. F. (2004). Inhaled anesthetic enhancement of amyloid-β oligomerization and cytotoxicity. Anesthesiology, 101(3), 703–709. https://doi.org/10.1097/00000542-200409000-00019  

5. Zhang, B., Dong, Y., Zhang, G., Moir, R. D., Xia, W., Yue, Y., Tian, M., Culley, D. J., Crosby, G., Tanzi, R. E., & Xie, Z. (2008). The inhalation anesthetic desflurane induces caspase activation and increases amyloid β-protein levels under hypoxic conditions *. Journal of Biological Chemistry, 283(18), 11866–11875. https://doi.org/10.1074/jbc.M800199200  

6. Planel, E., Richter, K. E. G., Nolan, C. E., Finley, J. E., Liu, L., Wen, Y., Krishnamurthy, P., Herman, M., Wang, L., Schachter, J. B., Nelson, R. B., Lau, L.-F., & Duff, K. E. (2007). Anesthesia leads to tau hyperphosphorylation through inhibition of phosphatase activity by hypothermia. Journal of Neuroscience, 27(12), 3090–3097. https://doi.org/10.1523/JNEUROSCI.4854-06.2007  

7. Nicolson, S. C., Montenegro, L. M., Cohen, M. S., O’Neill, D., Calfin, D., Jones, L. A., & Jobes, D. R. (2010). A comparison of the efficacy and safety of chloral hydrate versus inhaled anesthesia for sedating infants and toddlers for transthoracic echocardiograms. Journal of the American Society of Echocardiography: Official Publication of the American Society of Echocardiography, 23(1), 38–42. https://doi.org/10.1016/j.echo.2009.11.019  

8. Xiong, W.-X., Zhou, G.-X., Wang, B., Xue, Z.-G., Wang, L., Sun, H.-C., & Ge, S.-J. (2013). Impaired spatial learning and memory after sevoflurane–nitrous oxide anesthesia in aged rats is associated with down-regulated cAMP/CREB signaling. PLOS ONE, 8(11), e79408. https://doi.org/10.1371/journal.pone.0079408  

9. Yang, N., Li, L., Li, Z., Ni, C., Cao, Y., Liu, T., Tian, M., Chui, D., & Guo, X. (2017). Protective effect of dapsone on cognitive impairment induced by propofol involves hippocampal autophagy. Neuroscience Letters, 649, 85–92. https://doi.org/10.1016/j.neulet.2017.04.019  

10. Papáčková, Z., & Cahová, M. (2014). Important role of autophagy in regulation of metabolic processes in health, disease and aging. Physiological Research, 63(4), 409–420. https://doi.org/10.33549/physiolres.932684  

11. Zhang, X., Zhou, Y., Xu, M., & Chen, G. (2016). Autophagy is involved in the sevoflurane anesthesia-induced cognitive dysfunction of aged rats. PLOS ONE, 11(4), e0153505. https://doi.org/10.1371/journal.pone.0153505  

12. Zurek, A. A., Yu, J., Wang, D.-S., Haffey, S. C., Bridgwater, E. M., Penna, A., Lecker, I., Lei, G., Chang, T., Salter, E. W. R., & Orser, B. A. (2014). Sustained increase in α5GABA_A receptor function impairs memory after anesthesia. The Journal of Clinical Investigation, 124(12), 5437–5441. https://doi.org/10.1172/JCI76669  

13. Bonin, R. P., & Orser, B. A. (2008). GABA_A receptor subtypes underlying general anesthesia. Pharmacology Biochemistry and Behavior, 90(1), 105–112. https://doi.org/10.1016/j.pbb.2007.12.011 

14. Ling, Y., Ma, W., Yu, L., Zhang, Y., & Liang, Q. (2015). Decreased PSD95 expression in medial prefrontal cortex (mPFC) was associated with cognitive impairment induced by sevoflurane anesthesia. Journal of Zhejiang University-SCIENCE B, 16(9), 763–771. https://doi.org/10.1631/jzus.B1500006  

Famotidine is a histamine-2 receptor antagonist [1]. While it has traditionally been used to quell gastric acid production, recent clinical data suggests that famotidine may reduce COVID-19-associated morbidity and mortality [1, 2]. It is widely available in low-cost forms, either as generic or branded medications, and its pharmacology is well-documented [Malone]. Accordingly, if famotidine is resolutely found to be an effective COVID-19 treatment, it could be incredibly useful in controlling the ongoing pandemic.

Early studies were optimistic about the efficacy of famotidine. Freedberg et al. conducted a retrospective cohort study (n = 1,620) [1]. The subjects of the study were COVID-19 patients who had been administered either 10, 20, or 40 mg doses of the drug while they were infected [1]. Overall, people who received famotidine experienced a significantly reduced risk of intubation and death compared to people who did not receive the medication, indicating that famotidine is highly effective [1]. Subsequent studies have demonstrated similar results [2, 3].

Other studies have indicated that famotidine not only reduces COVID-19-related morbidity and mortality but also decreases the prevalence of certain symptoms. Janowitz and colleagues evaluated the effect of famotidine within a small cohort on five common symptoms: fatigue, anosmia, headaches, cough, and shortness of breath [4]. Among the ten COVID-19 patients analyzed, severity scores for all five symptoms significantly improved compared to baseline levels [4]. These patients had self-administered high-doses of famotidine orally, with the most common regime consisting of 80 mg ingested three times daily for a median duration of 11 days [4]. On a related note, Hogan et al. studied the relationship between famotidine and Acute Respiratory Distress Syndrome [5]. The 110 patients, all of whom had been placed on famotidine regimes, were intubated at significantly reduced rates, compared with COVID-19 patients who did not take famotidine [5]. 

Despite these promising results, not all studies have indicated that famotidine is particularly effective at countering COVID-19 or its adverse events [2]. Indeed, since Freedberg and colleagues’ early experiment, more recent studies have reported variable results [2]. For instance, an anonymous, web-based survey taken by 307 otolaryngology patients already on famotidine regimens found no association between the medication and incidence of COVID-19 [6]. 

One explanation for this discrepancy could be the differing dosage administered across studies. Many studies, especially those conducted retrospectively, have not published the amount of famotidine taken by their subjects, while other studies set dose levels at the standard used to treat gastroesophageal reflux disease (GERD) [2]. An early case series indicated that to effectively treat COVID-19, patients must receive famotidine at higher-than-standard doses [2]. While more evidence is needed to corroborate this theory, it could help explain the difference in results reported across scientific studies. 

Another question related to famotidine warranting further investigation is its mechanism of action against COVID-19. Malone and colleagues advanced a compelling theory: famotidine may block the histamine H2 receptor, which is implicated in the development of clinical COVID-19 [2]. The medication may also activate other G Protein-Coupled Receptors (GPCRs) [2]. Strong evidence supports these theories, but they warrant further investigation to be confirmed.

References 

[1] D. E. Freedberg et al., “Famotidine Use Is Associated With Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study,” Gastroenterology, vol. 159, no. 3, p. 1129-1131.E3, September 2020. [Online]. Available: https://doi.org/10.1053/j.gastro.2020.05.053. 

[2] R. W. Malone et al., “COVID-19: Famotidine, Histamine, Mast Cells, and Mechanisms,” Frontiers in Pharmacology, Updated March 23, 2021. [Online]. Available: https://doi.org/10.3389/fphar.2021.633680. 

[3] J. F. Mather, R. L. Seip, and R. G. McKay, “Impact of Famotidine Use on Clinical Outcomes of Hospitalized Patients With COVID-19,” American Journal of Gastroenterology, vol. 115, no. 10, p. 1-7, August 2020. [Online]. Available: https://doi.org/10.14309/ajg.0000000000000832. 

[4] T. Janowitz et al., “Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series,” Gut, vol. 69, no. 9, p. 1592-1597, June 2020. [Online]. Available: https://doi.org/10.1136/gutjnl-2020-321852. 

[5] R. B. Hogan II et al., “Dual-histamine receptor blockade with cetirizine – famotidine reduces pulmonary symptoms in COVID-19 patients,” Pulmonary Pharmacology & Therapeutics, vol. 63, p. 1-7, August 2020. [Online]. Available: https://doi.org/10.1016/j.pupt.2020.101942. 

[6] B. Balouch et al., “Role of Famotidine and Other Acid Reflux Medications for SARS-CoV-2: A Pilot Study,” Journal of Voice, January 2021. [Online]. Available: https://doi.org/10.1016/j.jvoice.2021.01.007. 

Literature demonstrates that anywhere from 0.2 – 2.2% of pregnant women undergo non-obstetric surgeries and anesthesia per year [1, 2]. The decision to proceed with surgery and anesthesia during pregnancy requires special attention to several maternal adaptations that occur during pregnancy, including changes in maternal blood volume and cardiac output, alterations in acid-base and respiratory status, increased hypercoagulability, reduced lower esophageal sphincter tone, increased gastric volume and acidity, and increased sensitivity to opioids and inhalation agents [2]. In addition to physiological changes, actual timing of surgery in relation to trimester matters significantly for reducing poor fetal outcomes [1-3].

With respect to timing, it is commonly accepted that surgery during the first trimester should be avoided unless emergent [1-3]. Most researchers and practitioners advocate for surgery and anesthesia during the third trimester due to the completion of organogenesis by this period [1-3]. However, a 16-year retrospective, matched case-control, cohort study by Devroe et al., which examined the use of anesthesia for non-obstetric operations, demonstrated increased incidence overall of preterm births in the surgical group and increased risk of preterm birth secondary to surgery in the third trimester. Within the surgical group, the study did not find significant associations between the overall incidence of preterm births and the trimester during which surgery was performed.

Timing aside, another factor to consider is the use of general vs. regional anesthesia. The common consensus is to use local anesthesia whenever possible, in order to avoid systemic transfer of the anesthetic to the fetus. Kuczkowski 2004 explains that virtually every drug and inhalation anesthetic is considered teratogenic to some fetuses under certain conditions, and thus, there is no “best” anesthetic agent to use. He also highlights that the commonly deployed nitrous oxide (NO) has been shown to oxidize vitamin B12, and interfere with tetrahydrofolate regeneration and DNA synthesis. Some studies have experimented with using B12 and folic acid prophylaxis when using NO in pregnant women, however the benefit of doing so is not clinically apparent.

A contrasting opinion on NO use can be found in Ramirez et al.’s paper, which argued that nitrous oxide is a weak teratogen whose reproductive effects only occur after prolonged exposure and high concentrations, conditions unlikely to be met in pregnant women undergoing surgery. However, Devroe et al.’s study demonstrated a statistically significant increase in low birth rates in women exposed to general anesthesia, which often included the use of NO. The differences in opinions in these studies highlight the ongoing discourse surrounding the use and safety of anesthesia in pregnancy, however, medical professionals should always choose anesthetics with the highest track record of safety in pregnant women and optimize their use during surgery.

Finally, as aforementioned in the first paragraph, the physiological changes that happen during pregnancy are many and can complicate routine surgery. For these reasons, it is important to closely monitor parameters such as blood pressure, heart rate, oxygenation and respiratory status intraoperatively to avoid maternal and/or fetal complications [3]. Aortocaval compression is of particular concern during surgery, as pregnant women positioned on their backs can suffer bouts of decreased blood pressure and cardiac output secondary to inferior vena cava compression. The decrease in blood pressure can lead to decreased placental perfusion, hypoxia, and fetal acidosis and poor fetal outcomes. Fetal heart rates (FHR) have been shown to decrease in hypoxic environments and can thus serve as a useful gauge of hypoxia intraoperatively [3]. Lastly, because the stress of surgery can cause premature contractions, deployment of a tocodynamometer can be a valuable asset during surgery. All in all, though complicated and multifactorial, surgery during pregnancy is sometimes necessary and requires thorough planning and safety optimization.

References 

1. Devroe, S., Bleeser, T., Van de Velde, M., Verbrugge, L., De Buck, F., Deprest, J., … & Rex, S. (2019). Anesthesia for nonobstetric surgery during pregnancy in a tertiary referral center: a 16-year retrospective, matched case-control, cohort study. International journal of obstetric anesthesia, 39, 74-81.DOI:10.1097/01.aoa.0000661412.51134.86 

2. Ramirez, V., Valencia, G., & Catalina, M. (2020). Anesthesia for nonobstetric surgery in pregnancy. Clinical obstetrics and gynecology, 63(2), 351-363. DOI:10.1097/GRF.0000000000000532

3. Kuczkowski, K. M. (2004). Nonobstetric surgery during pregnancy: what are the risks of anesthesia?. Obstetrical & gynecological survey, 59(1), 52-56. DOI:10.1097/01.OGX.0000103191.73078.5F

Every year in the United States, at least 1,500 to 2,000 retained surgical items (RSIs) are discovered in the bodies of postsurgical patients (1). Retained surgical items, also known as retained surgical foreign bodies (RFBs), include instruments, needles, sponges, and other materials used in a prior surgery. RSIs threaten the safety and survival of patients, with around 70% sustaining minor complications and 15% suffering severe harm (2). Surgical instruments, like forceps, can puncture organs and cause immediate damage; more frequently, however, cotton surgical materials, or “sponges,” are left behind, resulting in a gossypiboma that can cause obstruction, infection, sepsis, and death (3). Most commonly occurring in the abdominal, thoracic and pelvic cavities (4), RSIs present a serious threat to patient safety and typically require reoperation to be removed (2-4). However, with the right operating room culture and perioperative procedures, the occurrence of RSIs can be significantly minimized.

The risk factors associated with RSIs fall into two categories: the characteristics of the operation and perioperative procedure errors. First, although little research has been conducted on surgical errors such as RSIs, the current literature suggests positive associations between RSI occurrences and emergency operations, prolonged procedures, and multiple operative teams (1, 2). However, perioperative procedure errors more commonly resulted in RSIs, including incorrect instrument and sponge counts and poor communication (1, 3). In roughly 80% of RSI cases involving sponges — the most common RSI — the sponge count performed at the end of the surgery was erroneously called correct (4, 5). Incomplete body cavity examinations and incorrect instrument counts often stem from communication and cooperation problems between the surgeons and nurses, i.e. failing to work together to rectify an incorrect count or the dismissal of requests to look for missing items (1, 4). Moreover, some studies suggest that the communication errors that result in RSIs originate from the operating room “culture,” or the social ecosystem involving relationships between members of a surgical team (1, 3, 4).

Like other surgical errors, RSI cases are completely preventable. Hospitals around the country that have implemented perioperative and systematic strategies to prevent the retention of any surgical object have significantly decreased RSI cases (6). Using only radiopaque materials — such as gauze pads with x-ray markers — intracorporeally and performing x-rays to identify any missing materials before closing the incision are a vital preventative method that can take place perioperatively (1, 4, 7). Creating a standardized and robust counting system for each type of surgical material, often by using designated dry-erase boards or discrete plastic holders, constitutes one of the most successful preventative techniques (1, 4). Additionally, as some researchers argue that the communication errors that result in RSIs are systematic, changing the “culture” of the operating room is often necessitated (1). Encouraging communication and collaboration between all members of the surgical team remains one of the most important methods needed to reduce the incidence of retained surgical items.

References

1: Gibbs, V. 2011. Retained surgical items and minimally invasive surgery. World Journal of Surgery, vol. 35. DOI: 10.1007/s00268-011-1060-4.

2: Steelman, V., Shaw, C., Shine, L. and Hardy-Fairbanks, A. 2018. Retained surgical sponges: a descriptive study of 319 occurrences and contributing factors from 2012 to 2017. Patient Safety in Surgery, vol. 12. DOI: 10.1186/s13037-018-0166-0.

3: Feldman, D. 2011. Prevention of retained surgical items. Mount Sinai Journal of Medicine, vol. 78. DOI: 10.1002/msj.20299.

4: Gibbs, V., Coakley, F. and Reines, H. Preventable errors in the operating room: retained foreign bodies after surgery — part I. 2007. Current Problems in Surgery, vol 44. DOI: 10.1067/j.cpsurg.2007.03.002.

5: Kaiser, C., Friedman, S., Spurling, K., Slowick, T. and Kaiser, H. 1996. The retained surgical sponge. Annals of Surgery, vol. 224. DOI: 10.1097/00000658-199607000-00012.

6: Weprin, S., Crocerossa, F., Meyer, D., Maddra, K., Valancy, D., Osardu, R., Kang, H., Moore, R., Carbonara, U., Kim, F. and Autorino, R. 2021. Risk factors and preventive strategies for unintentionally retained surgical sharps: a systematic review. Patient Safety in Surgery, vol. 15. DOI: 10.1186/s13037-021-00297-3.

7: Hariharan, D. and Lobo, D. 2013. Retained surgical sponges, needles and instruments. Annals of the Royal College of Surgeons of England, vol. 95. DOI: 10.1308/003588413X13511609957218.

Pfizer, the company that collaborated to create the first mRNA coronavirus vaccine to receive emergency use authorization, is now seeking emergency use authorization from the FDA for its Covid-19 antiviral pill. On November 5, Pfizer announced in a press release that its new oral antiviral treatment, Paxlovid, significantly reduced the risk of hospitalization and death from COVID-19 (Pfizer, 2021). Interim analysis of the data from Pfizer’s Phase 2-3 clinical trials found that “among participants who received treatments within three days of Covid-19 symptoms starting, the risk of COVID-related hospital admission or death from any cause was 89% lower in the Paxlovid group than the placebo group” (Mahase, 2021).

The Paxlovid trial included 1,219 participants with a coronavirus infection at higher risk of developing severe COVID-19 (Citroner, 2021). In the study, participants were randomized 1:1, with half receiving a placebo pill and the other half receiving Paxlovid (Mahase, 2021). Of the participants who were treated within three days of symptom onset, 0.8% of patients who received Paxlovid were hospitalized up to day 28 after randomization, and no deaths occurred. In the comparison group of participants who were given a placebo, 7% of patients were admitted to the hospital, with seven deaths (Pfizer, 2021). Similar reductions were seen in participants treated within five days of symptom onset. Overall, throughday 28, “no deaths were reported among patients who received Paxlovid, while 10 people (1.6%) in the placebo group died” (Mahase, 2021). “[This news] is a real game-changer in the global efforts to halt the devastation of this pandemic,” said Albert Bourla, chairman and CEO of Pfizer, in a statement (Pfizer, 2021). “These data suggest that our oral antiviral candidate, if approved or authorized by regulatory authorities, has the potential to save patients’ lives, reduce the severity of COVID-19 infections, and eliminate up to nine out of ten hospitalizations,” he continued.

So how does Paxlovid work? Antiviral drugs like Paxlovid inhibit a virus’ ability to infect or replicate inside our cells. The coronavirus “wreaks havoc on the body” by inserting itself into cells, and then hijacking cell machinery to make copies of itself. Those copies then burst out of the cells and “invade other cells, spreading through the body” (Hickok, 2021). Paxlovid consists of two components: “an experimental molecule called PF-07321332 and an existing drug called ritonavir. Both are protease inhibitors, which means they block an enzyme (called a protease) that cuts apart long strands of nonfunctional viral proteins into smaller, functional proteins” (Hickok, 2021). In essence, Paxlovid aims to stop the coronavirus from replicating. “These drugs can be administered at any stage of the infection based on their mode of action,” said Fenyong Liu, a virologist at the University of California, Berkeley. However, “because more severe complications and damage due to infection are always associated with later stages,” they will be more effective if they’re given in the early stages of the infection (Hickok, 2021). In the Paxlovid clinical trial, Pfizer started the treatment within five days of symptom onset.

Antiviral COVID drugs “arrived with minimal fanfare but represent the biggest advance yet in treating patients already infected with COVID-19,” says Monica Gandhi, professor of medicine and associate division chief of HIV, Infectious Diseases, and Global Medicine at UCSF / San Francisco General Hospital (Gandhi, 2021). Ahead of its approval, the UK purchased 250,00 courses of thePaxlovid; according to news reports, the Biden administration is “set to buy 10 million courses” of the pills (Pager et al., 2021). Millions of Americans remain unvaccinated, while millions more around the globe still don’t have access to the vaccine; as such, the need and public demand for effective medication to reduce the severity of symptoms for both unvaccinated and vaccinated patients alike remain evident.

References 

Citroner, G. (2021, November 8). Pfizer antiviral drug may be 90% effective against severe Covid-19: what we need to know. Healthline. https://www.healthline.com/health-news/pfizer-antiviral-drug-may-be-90-effective-against-severe-covid-19-what-to-know.

Gandhi, M. (2021, November 29). The new COVID drugs are a bigger deal than people realize. The Atlantic. https://www.theatlantic.com/ideas/archive/2021/11/covid-drugs-molnupiravir-paxlovid-treatment-antiviral/620819/.

Hickok, K. (2021, November 12). How Covid antiviral pills work and what that could mean for the pandemic. NBC News. https://www.nbcnews.com/health/health-news/covid-antiviral-drugs-merck-pfizer-pills-work-rcna5317.

Mahase E. (2021, November 8). Covid-19: Pfizer’s Paxlovid is 89% effective in patients at risk of serious illness, company reports. BMJ doi:10.1136/bmj.n2713

Pager et al. (2021, November 16). Biden administration to buy Pfizer antiviral pills for 10 million people, hoping to transform pandemic. The Washington Post. https://www.washingtonpost.com/health/2021/11/16/administration-purchases-pfizer-anti-covid-pill/.

Pfizer, Inc. (2021, November 5). Pfizer’s Novel COVID-19 Oral Antiviral Treatment Candidate Reduced Risk of Hospitalization or Death by 89% in Interim Analysis of Phase 2/3 EPIC-HR Study. Business Wire. https://www.businesswire.com/news/home/20211105005260/en/