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Whether a patient consumes healthy amounts of alcohol regularly or suffers from alcohol abuse, anesthesia providers must alter their strategy before, during, and after surgery to promote the best outcomes. 

In the preoperative period, understanding the patient’s history of alcohol consumption is paramount [1]. Adults and adolescents should be administered an established fluid questionnaire, such as those designed by the National Institute on Alcohol Abuse and Alcoholism, to track past and present consumption patterns [1]. If a patient suffers from chronic alcohol misuse, elective operations may need to be more carefully considered in light of heightened risk [2]. Ideally, patients should abstain from drinking for six to eight weeks before surgery to minimize their risk of complications [2]. To achieve successful preoperative sobriety, clinicians can refer the patient to a withdrawal program [2].

Before the operation, clinicians should examine the patients’ nervous system, cardiovascular system, and liver to test whether the patient shows indications of diminished cognitive function, impaired vision, autonomic or peripheral neuropathies, difficulties with coordination, cardiac failure, arrhythmias, and hypertension [1]. An EKG and chest x-ray may be appropriate [1].

Following these examinations, the anesthesia provider must determine what type of anesthesia at what level of dosage is appropriate for the patient [3]. Alcohol’s deleterious effect on liver function makes it more difficult for the liver to metabolize anesthetic agents [3]. Alcohol users also experience relatively blunted nerve receptors, so they can possibly achieve the numbing effects of anesthesia with less medication [3]. Consequently, patients with a history of chronic alcohol usage may require lower doses of anesthesia [3, 4]. However, the effects of specific anesthetic agents may change the anesthesia provider’s approach to dosage. For instance, research found that alcoholic patients required a higher induction dose of propofol on average, suggesting that the “less is more” rule does not always apply [5].

During surgery, patients with a history of alcohol consumption are likely to benefit from rapid sequence induction to prevent intraoperative complications [1]. Because alcohol can lower a patient’s blood pressure (BP), especially if consumed in the period leading up to surgery, anesthesia providers must be careful to track BP throughout the procedure [3]. For chronic alcohol users, intraoperative alcohol withdrawal syndrome (AWS) may be possible [6]. Although researchers have yet to identify the causes of intraoperative AWS with certainty, anesthesia providers should anticipate its occurrence, especially if they note local anesthetic systemic toxicity [6]. 

Anesthesia providers and surgeons must be attentive to potential postoperative complications, particularly in patients with substance dependence or who were not sober before surgery. Chronic alcohol users have a 2- to 5-fold greater risk of complication [1]. AWS may result in adverse cardiovascular or neurological events such as delirium, tachycardia, and seizures [7]. Other complications, such as bleeding, heightened stress responses, and immune deficiency, can also occur [1]. Some of these symptoms can be treated with benzodiazepines, thiamine supplementation, or, more rarely, propofol [2, 7]. 

Because the range of alcohol-related complications is great and the risk high, a patient’s history with drinking must be a major consideration for all anesthesia providers throughout the surgical process. Although the likelihood of adverse events varies depending on how often and how much a patient drinks, clinicians should never ignore these considerations when alcohol is a prominent part of a patient’s lifestyle. 

References 

[4] B. Wolfson and B. Freed, “Influence of Alcohol on Anesthetic Requirements and Acute Toxicity,” Anesthesia & Analgesia, vol. 59, no. 11, p. 826-830, November 1980. [Online]. Available: https://pubmed.ncbi.nlm.nih.gov/7191671/. 

[5] J. I. Choi et al., “Effects of chronic alcohol consumption on propofol-induced sedation in spinal anesthesia,” European Journal of Anaesthesiology, vol. 22, no. 1, p. 98, May 2005. [Online]. Available: https://pubmed.ncbi.nlm.nih.gov/7191671/. 

[3] M. Fathi, “Anesthetic Considerations for Alcohol Using Patients,” Asia Pacific Journal of Medical Toxicology, vol. 3, supp. 1, p. 17, May 2014. [Online]. Available: http://www.doi.org/10.22038/APJMT.2014.2896. 

[2] T. Blincoe and D. Chambler, “Alcohol and anaesthesia,” British Journal of Hospital Medicine, vol. 80, no. 8, August 2019. [Online]. Available: http://www.doi.org/10.12968/hmed.2019.80.8.485. 

[7] C. Adams, “Anaesthetic implications of acute and chronic alcohol abuse,” Southern African Journal of Anaesthesia and Analgesia, vol. 16, no. 3, p. 42-49, November 2010. [Online]. Available: http://www.doi.org/10.1080/22201173.2010.10872680. 

[6] A. Subedi and B. Bhattarai, “Intraoperative Alcohol Withdrawal Syndrome: A Coincidence or Precipitation?,” Case Reports in Anesthesiology, vol. 2013, no. 3, p. 1-3, July 2013. [Online]. Available: http://www.doi.org/10.1155/2013/761527. 

[1] R. Chapman and F. Plaat, “Alcohol and anaesthesia,” Continuing Education in Anaesthesia, Critical Care & Pain, vol. 9, no. 1, p. 1-3, December 2009. [Online]. Available: http://www.doi.org/:10.1093/bjaceaccp/mkn045. 

The World Health Organization defines anaphylaxis as a severe, life-threatening generalized or systemic hypersensitivity reaction, which is usually mediated by an immunologic mechanism, resulting from the sudden release of IgE, IgG, complements, or immune complexes [1,2]. Foods and medications (such as the exceedingly rare instances associated with COVID-19 vaccination) are the cause of most situations for which a cause can be identified, but any agent capable of directly or indirectly activating mast cells or basophils can lead to anaphylaxis [2].

Anaphylactic reactions can present with the following signs and symptoms: diffuse erythema (redness), pruritis (itchiness), urticaria (hives), angioedema (swelling), bronchospasm, laryngeal edema (swelling in the throat), hyperperistalsis, hypotension (low blood pressure), and cardiac arrhythmias [2]. Other symptoms that may accompany an anaphylactic reaction include nausea, vomiting, lightheadedness, headache, anxiety, and unconsciousness [2]. Generalized urticaria and angioedema are the most common clinical presentations [2]. Signs and symptoms may not present simultaneously [2]. The more rapid the onset of the signs and symptoms after exposure to an offending stimulus, the more likely the reaction will be severe and possibly life-threatening [2]. Anaphylaxis typically occurs within 5 to 30 minutes [2].

Estimates of anaphylaxis prevalence vary widely [3]. Several studies have suggested that prevalence is increasing, particularly in developed countries [3]. This is reflected by higher reported rates in all age groups in recent decades [1]. The increase in anaphylactic events is estimated to be as high as 350% for food-induced anaphylaxis and 230% for non-food induced anaphylaxis over the last ten years [1]. A 2014 study investigating the lifetime prevalence in the adult population in the United States found that at least 1 in every 50 adults experienced this one or more times [3]. Consistent with prior reports, the researchers found that medications, food, and stinging insects were the most frequent anaphylactic reaction triggers [3].

Numerous factors may affect its incidence, including previous history, atopy, socioeconomic factors, gender, geography, and season [1]. Previous history of anaphylaxis is considered to be the only known reliable predictor of future anaphylaxis [1]. However, at least 25% of adults and 65% of children presenting with an anaphylactic reaction do not report a previous event [1]. In adults, women are more likely to experience this reaction than men due to estrogens that enhance mast cell activation and allergic sensitization [1].

Treatment involves consideration of both the emergency treatment of acute reactions and long-term care that aims to reduce the risk of subsequent reactions [4]. In fatal episodes, death may occur within minutes of the reaction, underscoring the importance of effective emergency management [4]. Adrenaline/epinephrine, glucocorticosteroids, antihistamines, and methylxanthines have been shown to be effective interventions in the care of acute anaphylaxis [4]. Injectable adrenaline is universally agreed upon as the first-line therapy for anaphylaxis [6]. It is able to counteract many pathophysiological changes in anaphylactic reactions by acting through alpha-1 adrenergic receptors to induce vasoconstriction, which prevents airway edema and hypotension. It also binds to beta-1 and beta-2 adrenergic receptors to increase heart rate and airway dilation [6]. Long-term management of anaphylaxis typically involves carrying an adrenaline autoinjector [5].

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References

1. Ben-Shoshan, M., & Clarke, A. (2010). Anaphylaxis: past, present and future. Allergy, 66(1), 1-14. doi:10.1111/j.1398-9995.2010.02422.x

2. Kemp, S., & Lockey, R. (2002). Anaphylaxis: A review of causes and mechanisms. Journal of Allergy and Clinical Immunology, 110(3), 341-348. doi:10.1067/mai.2002.126811

3. Wood, R., Camargo, C., Lieberman, P. et al. (2014). Anaphylaxis in America: The prevalence and characteristics of anaphylaxis in the United States. Journal of Allergy and Clinical Immunology, 133(2), 461-467. doi:10.1016/j.jaci.2013.08.016

4. Dhami, S., Panesar, S., Roberts, G. et al. (2013). Management of anaphylaxis: a systematic review. Allergy, 69(2), 168-175. doi:10.1111/all.12318

5. de Silva, D., Singh, C., Muraro, A. et al. (2020). Diagnosing, managing and preventing anaphylaxis: Systematic review. Allergy. doi:10.1111/all.14580

6. Reber, L., Hernandez, J., & Galli, S. (2017). The pathophysiology of anaphylaxis. Journal of Allergy and Clinical Immunology, 140(2), 335-348. doi:10.1016/j.jaci.2017.06.003

Over the last decade, the number of liver transplantation surgeries conducted has increased vastly [1]. With this increase, postoperative rates of survival are improving as well [1]. However, the likelihood of patients experiencing postoperative complications has also risen [1]. Acute kidney injury (AKI) is one of the most pressing complications for physicians to consider, given its frequency and deadliness following liver transplant surgery [2]. To combat AKI, medical practitioners need to understand its causes and comorbidities.

Among the risk factors for AKI, most are preoperative [2]. A 5-year retrospective study of 424 patients found that female sex, a weight greater than 100 kg, pre-existing diabetes mellitus, and severity of liver disease (indicated by a high Child-Pugh score) dramatically increase a patient’s risk of developing AKI [3]. Genetic factors may also play a role. One study found that patients who had the IL4-33 T/T genotype were more likely to develop AKI than those with alternate genotypes [2]. The researchers believe this association could emerge from the gene’s effect on inflammatory and anti-inflammatory cytokines, which impact the development of AKI [2]. Another preoperative predictor of AKI may be a higher body mass index (BMI) [4]. However, researchers offer this conclusion with a caveat, given how end-stage liver disease can render BMI an inaccurate measure of body composition [4].

Intraoperative risk factors are also important to note. One significant risk factor is the loss of blood during surgery, accompanied by transfusion of either red blood cells or plasma, which are associated with AKI [2, 3, 4]. Some studies have suggested that blood loss and transfusion significantly increase the risk of AKI when occurring in large quantities and when the blood that patients receive has been stored for a long time [2]. Hypotension is also a risk factor, with AKI incidence increasing the longer a patient’s mean arterial pressure (MAP) is less than 65 mmHg [5]. Other cardiac risks include elevated baseline right ventricular end-diastolic volume and baseline central venous pressure following the administration of anesthesia [2]. Additionally, longer surgeries (>480 minutes) are associated with a higher risk of developing AKI [2].

Certain factors related to the donor liver also increase the risk of AKI in certain liver transplant recipients. One study followed 88 liver transplant recipients whose liver donations came from victims of cardiac death [6]. The researchers found that these patients experienced a greater incidence of AKI following surgery, compared to patients who had received donation after brain death [6]. Scientists also noted how hepatic ischemic reperfusion injury consistently predicted postoperative renal dysfunction [6]. Other experiments have corroborated these findings by demonstrating how warm and cold donor liver ischemia time is strongly associated with AKI [2]. 

Unfortunately, AKI is a condition for which no effective treatment has yet been developed [2].  Therefore, it is integral that physicians take these risk factors into account to mitigate the likelihood of this condition. 

References 

[1] F. M. Carrier et al., “Effects of intraoperative hemodynamic management on postoperative acute kidney injury in liver transplantation: An observational cohort study,” PLoS One, vol. 14, no. 8, p. 1-14, August 2020. [Online]. Available: https://doi.org/10.1186/s12871-020-01228-y. 

[2] I. M. Iljinsky and O. M. Tsirulnikova, “New trends in the study of post-transplant acute kidney injury after liver transplantation,” Vestnik Transplantologii I Iskusstvennyh Organov, vol. 21, no. 4, p. 108-120, February 2020. [Online]. Available: https://doi.org/10.15825/1995-1191-2019-4-108-120. 

[3] I. A. Hilmi et al, “Acute kidney injury following orthotopic liver transplantation: incidence, risk factors, and effects on patient and graft outcomes,” British Journal of Anaesthesia, vol. 114, no. 6, p. 919-926, June 2015. [Online]. Available: https://doi.org/10.1093/bja/aeu556.  

[4] A. Mrzljak et al, “Pre- and intraoperative predictors of acute kidney injury after liver transplantation,” World Journal of Clinical Cases, vol. 8, no. 18, p. 4034-4042, September 2020. [Online]. Available: https://doi.org/10.1093/bja/aeu556. 

[5] A. Joosten et al., “Intraoperative hypotension during liver transplant surgery is associated with postoperative acute kidney injury: a historical cohort study,” BMC Anesthesiology, vol. 21, no. 1, p. 1-10, January 2021. [Online]. Available: https://doi.org/10.1186/s12871-020-01228-y.  

[6] J. A. Leithead et al, “Donation After Cardiac Death Liver Transplant Recipients Have an Increased Frequency of Acute Kidney Injury,” American Journal of Transplantation, vol. 12, no. 4, p. 965-975, January 2012. [Online]. Available: https://doi.org/10.1111/j.1600-6143.2011.03894.x.  

The majority of anesthesia care in the United States is safely and effectively provided by teams with both anesthesiologists and Certified Registered Nurse Anesthetists (CRNAs) [1]. Currently, all 50 states utilize anesthesia care teams composed of both anesthesiologists and CRNAs [1].

Until the establishment of anesthesiology as a medical specialty in the United States in the mid-19^th century, anesthesia care for surgical patients was mainly provided by trained nurses under the supervision of surgeons [1,2]. As the number of anesthesiologists substantially increased between 1970 and 2000, anesthesia care teams became a popular concept in hospitals [1]. The anesthesia care team is led by anesthesiologists who supervise or medically direct CRNAs [2]. CRNAs are advanced practice registered nurses who receive master’s level education and pass national board certification in the nurse anesthesia specialty [1]. Depending on the circumstances, one anesthesiologist can oversee up to four CRNAs [2]. The supervising anesthesiologist attends key events in anesthetic management, including pre-anesthesia evaluation, induction, emergence, placement of invasive monitoring, post-operative care, and any emergent conditions [2]. By 2007, there were 42,330 anesthesiologists and 36,000 CRNAs registered as anesthesia care providers [1]. In 2019, the anesthesia workforce became balanced with approximately the same number of practicing CRNAs as anesthesiologists (~50,000) [2].

In the United States, the scope of practice for anesthesia providers is determined uniquely by individual state governments [2]. Approximately 65% of CRNAs practice in collaboration with anesthesiologists; 17 states allow CRNAs to practice independently [1,2]. In these states, CRNAs tend to be the sole anesthesia providers, often working in rural hospitals to provide surgical and obstetrical services, trauma stabilization, and interventional diagnostic and pain management capabilities [2,3]. Because CRNAs are able to practice independently in certain areas in the United States, fewer regions experience a shortage of anesthesia care providers that could result in delay or cancellation of surgery [1,3].

The impact of anesthesia provider credentials on patient outcomes frequently has been a research topic [4]. In 2004, researchers in the United Kingdom completed an extensive literature review and concluded that it was not possible to draw a conclusion regarding the differences in patient outcomes as a result of anesthesia provider type [5]. The researchers cited many limitations of previous studies, such as failure to properly define how hospital anesthesia providers are utilized and lack of consideration for resources and systems beyond the anesthesia provider that may impact outcomes [4,5].

In 2009, researchers at Emory University reexamined the impact of anesthesia providers on outcomes, accounting for relevant nursing, medical, and anesthesia resources [4]. The study focused specifically on obstetrical anesthesia and maternal outcomes [4]. The results of the study indicated that hospitals that utilize only CRNAs or anesthesia care teams do not have systematically higher rates of maternal complications [4].

The presence of both CRNAs and anesthesiologists in the anesthesia workforce has facilitated an expansion of anesthesia providers in the United States to match rapidly growing surgical numbers [6]. In states requiring supervision of CRNAs, the anesthesia care team model allows anesthesiologists the flexibility to be outside of the operating room to participate in administrative, research, training, quality, and safety-related activities [2]. In states allowing CRNAs to independently practice, many facilities that otherwise would not have access to anesthesia care benefit from CRNA expertise [4].

References 

1. Matsusaki, T., & Sakai, T. (2011). The role of Certified Registered Nurse Anesthetists in the United States. Journal of Anesthesia, 25(5), 734-740. doi:10.1007/s00540-011-1193-5

2. Atkins, J. (2019). The Anesthesiology Care Team: Who, How, Why? Translational Perioperative and Pain Medicine, 7(1). doi:10.31480/2330-4871/108

3. Gunn, I. P. (2000). Rural health care and the nurse anesthetist. CRNA: The Clinical Forum for Nurse Anesthetists, 11(2), 77. PMID:11271044 

4. Needleman, J., & Minnick, A. (2009). Anesthesia Provider Model, Hospital Resources, and Maternal Outcomes. Health Services Research, 44(2p1), 464-482. doi:10.1111/j.1475-6773.2008.00919.x

5. Smith, A., Kane, M., & Milne, R. (2004). Comparative effectiveness and safety of physician and nurse anaesthetists: a narrative systematic review. British Journal of Anaesthesia, 93(4), 540-545. doi:10.1093/bja/aeh240

6. Patricia, K. (2019). Anesthesiology Workforce Challenges in the U.S. Translational Perioperative and Pain Medicine, 7(1). doi:10.31480/2330-4871/106

Outpatient health care environments have seen remarkable growth over the past decade. A major driving factor of this change has been the emergence of value-based care, which seeks to reward hospitals for delivering the highest-quality care at the lowest price. While the number of inpatient admissions has stayed relatively flat over the past fifty years, outpatient visits have increased exponentially. In 1975, there were around 250,000 outpatient admissions—in 2015, there were more than 800,000. [1]

These patterns have led many hospitals to shift their revenue structure toward outpatient care, according to a recent study by Deloitte. In 1994, outpatient care accounted for just 28% of hospitals’ overall revenue. In 2020, outpatient care and inpatient care each account for nearly half of hospitals’ overall revenue.

The transition from inpatient to outpatient care can be jarring for physicians. The intense nature of inpatient care is satisfying for many physicians but also makes it difficult to develop long-term relationships with patients. When transitioning from inpatient to outpatient settings, physicians should consider the differences in these environments, as well as the impacts on their practice. 

One of the reasons that the shift between settings can catch physicians off guard is that inpatient and outpatient practitioners work in relatively distinct arenas. The separation between these two healthcare settings can make it difficult for medical practices and healthcare systems to communicate with each other about a patient’s health. Consequentially, physicians working in inpatient settings may have little experience interacting with outpatient physicians and vice-versa. A study by the Community Tracking Project found that this trend is not going away, either—in fact, inpatient and outpatient practitioners are drifting farther apart. [2]

The lifestyle of inpatient physicians is typically associated with long hours and a high-intensity workload. As a result, there is a common perception that hospitalists are at an increased risk of burnout as compared to their outpatient peers. However, there has been very little research to confirm the veracity of this statement. In fact, one study by Roberts et al. found that outpatient physicians frequently reported more emotional exhaustion from their work than their inpatient peers. [3] Additional research into the topic will help clarify what physicians can expect from a shift between practice settings.

There are some areas where physicians can expect little change, including the realm of malpractice claims. A study by Bishop et al. found that patients filed malpractice claims at the same levels for both inpatient and outpatient environments. [4] In outpatient environments, the most common claim was for diagnostic issues, while surgical issues were the primary reason for inpatient claims. In both cases, major injury or death were the most common outcomes.

The rise in telemedicine and advances in technology that allow more procedures to be done in outpatient environments have led more and more physicians to consider transitioning to outpatient work. The growth in telehealth was also accelerated by the COVID-19 pandemic, which pushed many providers to offer online services. [5]. These services allow for more flexible hours and the ability to work from home, which many physicians find appealing.

References 

[1] “2019 Physician Inpatient/Outpatient Revenue Survey.” Merritt Hawkins, 2019, www.merritthawkins.com/uploadedFiles/MerrittHawkins_RevenueSurvey_2019.pdf.

[2] Pham, Hoangmai H., et al. “Hospitalists And Care Transitions: The Divorce Of Inpatient And Outpatient Care: Health Affairs Journal.” Health Affairs, vol. 27, no. 5, Sept. 2008. doi:10.1377/hlthaff.27.5.1315.

[3] Roberts, Daniel L., et al. “Burnout in Inpatient-Based versus Outpatient-Based Physicians: A Systematic Review and Meta-Analysis.” Journal of Hospital Medicine, vol. 8, no. 11, Oct. 2013, pp. 653–664. doi:10.1002/jhm.2093.

[4] Bishop, Tara F. “Paid Malpractice Claims for Adverse Events in Inpatient and Outpatient Settings.” JAMA, vol. 305, no. 23, June 2011, p. 2427. doi:10.1001/jama.2011.813.

[5] Koonin, Lisa M. “Trends in the Use of Telehealth During the Emergence of the COVID-19 Pandemic – United States, January–March 2020.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 30 Oct. 2020, www.cdc.gov/mmwr/volumes/69/wr/mm6943a3.htm.

In an operation where inhalation anesthetics are used, some amount of those anesthetics are dispersed into the operation room. When that happens, medical staff may be exposed to trace amounts of these gases. While a single instance of exposure is likely negligible, over the course of a multi-decade career, more serious issues can emerge.

Research has not revealed a direct link between chronic exposure to low levels of anesthetic gases and specific long-term health conditions. However, hazards have not been definitively ruled out. A study by Mierdl et al. studied the presence of common inhalation anesthetics in surgeons, anesthesiologists and perfusionists, both before and after a surgery. The study found that all three roles had elevated levels of these gases after the surgery concluded. Surgeons and anesthesiologists showed the highest levels of concentration—up to 9 ppm for some gases [1].

Other studies have suggested a correlation between chronic exposure to inhalation anesthetics and reproductive toxicity. A study by Corbett et al. looked at birth defects in the children of nurse anesthetists. The children of those who worked during pregnancy had birth defects in 16.4% of cases, compared to 5.7% of those whose mothers did not work during pregnancy [2]. A more recent study by Jevtovic-Todorovic et al. exposed rats to varying levels of nitrous oxide and then tested the effects on a subset of neurons. The study found that high levels of short-term nitrous oxide exposure led to neuronal injury in adult rats. Long-term exposure resulted in neuron death [3]. In an article in Best Practice & Research Clinical Anesthesiology by Anton Burm, the author notes that these conditions were found when rats were exposed to concentrations of 1,000 ppm or higher, which can occur in poorly ventilated operating rooms [4].

Most studies suggest that, while chronic exposure to waste anesthetic gases may not cause immediate damage, it is still best to mitigate exposure. The Occupational Safety and Health Administration notes that, until the 1970s, it was common practice to exhaust waste gas using the expiratory valve, which often directs into the face of the anesthesia provider. Today, efficient scavenging systems capture these gases directly from the valve, significantly lowering exposure [5]. 

However, exposure still occurs, and frequent assessments are a useful way of determining the levels of exposure in an operating room. OSHA suggests sampling a known quantity of air and analyzing the levels of particulates using a flame-ionization detector [6]. A study by Sakhvidi et al. found that solid-phase microextraction (SPME) samplers can be a useful tool in determining occupational exposure. The study found it to be as reliable as the OSHA method and particularly useful in the operating room [7]. 

Short-term exposure to dispersed inhalation anesthetics likely has little permanent impact on subjects. However, chronic exposure has been correlated with certain health conditions. While there has been no conclusive evidence that exposure to waste anesthetic gases results in adverse health effects, most of the research on the topic concludes that healthcare professionals should avoid long-term exposure. Proper ventilation and testing were cited as two of the most common ways to assess and prevent exposure.

References 

[1] Mierdl, S., et al. “Occupational Exposure to Inhalational Anesthetics during Cardiac Surgery on Cardiopulmonary Bypass.” The Annals of Thoracic Surgery, vol. 75, no. 6, 2003, pp. 1924–1927., doi:10.1016/s0003-4975(03)00003-1.

[2] Corbett, T. H., et al. “Birth Defects among Children of Nurse-Anesthetists.” Anesthesiology, vol. 41, no. 4, 1974, pp. 321–344., doi:10.1097/00000542-197410000-00005.

[3] Jevtovic-Todorovic, V., et al. “Prolonged Exposure to Inhalational Anesthetic Nitrous Oxide Kills Neurons in Adult Rat Brain.” Neuroscience, vol. 122, no. 3, 2003, pp. 609–616., doi:10.1016/j.neuroscience.2003.07.012.

[4] Burm, Anton G. l. “Occupational Hazards of Inhalational Anaesthetics.” Best Practice & Research Clinical Anaesthesiology, vol. 17, no. 1, 2003, pp. 147–161., doi:10.1053/bean.2003.0271.

[5] OSHA Directorate of Technical Support and Emergency Management. “Anesthetic Gases: Guidelines for Workplace Exposures.” Waste Anesthetic Gases, Occupational Safety and Health Administration, 18 May 2000, www.osha.gov/dts/osta/anestheticgases/. 

[6] “Sampling and Analytical Methods: Enflurane Halothane Isoflurane – (Organic Method #103).” Sampling and Analytical Methods, Occupational Safety and Health Administration, www.osha.gov/dts/sltc/methods/organic/org103/org103.html. 

[7] Sakhvidi, M. J. Z., et al. “Field Application of SPME as a Novel Tool for Occupational Exposure Assessment with Inhalational Anesthetics.” Environmental Monitoring and Assessment, vol. 184, no. 11, 2011, pp. 6483–6490., doi:10.1007/s10661-011-2434-7.

Prehabilitation is a proactive approach to post-surgical rehabilitation that starts before the surgery even begins. The program is based on the assumption that enhancing the functional capacity of a patient will assist him or her in enduring the stressful postoperative period. A complete prehabilitation plan includes all members of the surgical team and involves the perioperative physician and anesthesiologist working in tandem to create a patient-centric plan in advance of a surgery [1].

Prehabilitation often begins with an assessment of functional capacity, which helps the surgical team understand the risks associated with a surgery for a specific patient. Ultimately, the goal is to improve an individual’s functional capacity [2]. Current approaches usually include exercise, dietary interventions, stress interventions and cessation of habits that lead to poor health such as smoking. As Carli and Feldman note in their review of studies on prehabilitation, the approach is not a “one size fits all” program, but rather requires an individualized program that takes into account each patient’s unique needs. [3]

Several studies have examined the efficacy of traditional programs. Gillis et al. observed 77 patients undergoing colorectal resection for cancer. Those who underwent prehabilitation were 22% more likely to recover to baseline exercise capacity 2 months after the surgery compared to those who did not [4]. A similar study by Howard et al. looked at patients undergoing major abdominal surgery. Those who underwent prehabilitation saw their systolic and diastolic blood pressures improve significantly faster than control patients. The study also found that, due to shorter recovery times and lower risk of complications, prehabilitation saved hospitals an average of $21,946 per patient [5].

Prehabilitation can prove particularly helpful to elderly patients, many of whom are frail or lead sedentary lives. Poor nutrition status, which is a risk factor for postoperative complications in adults, is also a common trait in elderly patients. A systematic review of studies focusing on postoperative outcomes in elderly general surgery patients by van Stijn et al. found that weight loss prior to surgery and serum albumin were significant preoperative indicators of postoperative outcome [6]. Indeed, when put into practice, a pre-operative program was found to reduce incidences of delirium in elderly patients from 11.7% in control groups to 8.2% in experimental groups [7].

While most efforts in this area have focused on physical measures, psychological prehabilitation can also protect against anxiety and depression, which sometimes emerge in patients who have undergone anesthesia. A systematic review of psychological prehabilitation for cancer patients by Tsimopoulou et al. found that these interventions appear to have positively affected patients’ immunologic function, as well as postoperative quality of life [8].

While prehabilitation has been around in one form or another since the 1940s, studies on the practice are relatively recent and have had small sample sizes. Currently, a series of large-scale studies are examining its impact on broader populations. While the concept is still in its infancy, existing research suggests that prehabilitation has the potential to improve care, enhance recovery, and lower costs.

References 

[1] Carli, Francesco. “Prehabilitation for the Anesthesiologist.” Anesthesiology, Published Ahead of Print, 2020. doi:10.1097/aln.0000000000003331. 

[2] Arena, Ross, et al. “Assessment of Functional Capacity in Clinical and Research Settings.” Circulation, vol. 116, no. 3, 2007, pp. 329–343. doi:10.1161/circulationaha.106.184461. 

[3] Carli, F., and L.s. Feldman. “From Preoperative Risk Assessment and Prediction to Risk Attenuation: a Case for Prehabilitation.” British Journal of Anaesthesia, vol. 122, no. 1, 2019, pp. 11–13. doi:10.1016/j.bja.2018.10.021. 

[4] Gillis, Chelsia, et al. “Prehabilitation versus Rehabilitation.” Anesthesiology, vol. 121, no. 5, 2014, pp. 937–947. doi:10.1097/aln.0000000000000393. 

[5] Howard, Ryan, et al. “Taking Control of Your Surgery: Impact of a Prehabilitation Program on Major Abdominal Surgery.” Journal of the American College of Surgeons, vol. 228, no. 1, 2019, pp. 72–80. doi:10.1016/j.jamcollsurg.2018.09.018. 

[6] Stijn, Mireille F. M. Van, et al. “Preoperative Nutrition Status and Postoperative Outcome in Elderly General Surgery Patients.” Journal of Parenteral and Enteral Nutrition, vol. 37, no. 1, 2012, pp. 37–43. doi:10.1177/0148607112445900. 

[7] Janssen, T. L., et al. “Multimodal Prehabilitation to Reduce the Incidence of Delirium and Other Adverse Events in Elderly Patients Undergoing Elective Major Abdominal Surgery: An Uncontrolled before-and-after Study.” Plos One, vol. 14, no. 6, 2019. doi:10.1371/journal.pone.0218152. 

[8] Tsimopoulou, Ioanna, et al. “Psychological Prehabilitation Before Cancer Surgery: A Systematic Review.” Annals of Surgical Oncology, vol. 22, no. 13, 2015, pp. 4117–4123. doi:10.1245/s10434-015-4550-z. 

The ongoing COVID-19 pandemic is caused by the emergence of the SARS-CoV-2 coronavirus. Without any adequate vaccine or therapeutics available at the moment, many researchers have turned their attention to prevention methods by studying the SARS-CoV-2 structure and its mechanism of cell entry. If the virus could be blocked from entering human cells, SARS-CoV-2 would be unable to replicate and invade the host immune system. Proteases essential for viral entry have been identified, and research reveals that protease inhibitors might be the key to stopping this infectious virus.

SARS-CoV-2 is closely related to SARS-CoV, a strain of coronavirus responsible for the SARS outbreak in 2003. Reports reveal that the two coronaviruses share 76 percent similarity in amino-acid sequence¹. Therefore, the mechanism in which SARS-CoV-2 enters host cells shares many similarities with that of SARS-CoV. From previous research, it has been determined that SARS-CoV relies on the protein angiotensin-converting enzyme 2 (ACE2) to enter host cells. The S1 unit of the spike protein of SARS-CoV-2 binds to ACE2, which is the host’s transmembrane endopeptidase. Infectivity of SARS-CoV-2 is then made possible by the serine protease TMPRSS2. TMPRSS2 is critical in facilitating the spread of the virus because the virus uses it for S protein priming on its surface. Cysteine protease cathepsin B and L (CatB/L) is another protease that performs the same function as TMPRSS2. S protein priming results in the fusion of viral and host membranes, subsequently completing viral cell entry². Heavy viral dependence on protease activity suggests that if protease inhibitors were utilized, SARS-CoV-2 infectivity could be eliminated.

Camostat mesilate is a commercial serine protease inhibitor that inhibits TMPRSS2 activity. Clinical trial results showed that camostat mesilate was successful in partially blocking SARS-CoV-2 entry into Caco-2 and Vero-TMPRSS2 cells. E-64d is an inhibitor of Catb/L, and when used conjunctively with camostat mesilate, full inhibition of viral entry was attained. The additive efficacy of the two inhibitors indicates that SARS-CoV-2 entry is driven by both TMPRSS2 and E-64d priming. However, S priming by TMPRSS2 is essential for viral cell entry, while CatB/L priming is not required for viral spread. Therefore, inhibitor drugs targeted at TMPRSS2 activity have become a more attractive option. Similar to past study results on SARS-CoV, camostat mesilate significantly reduced SARS-CoV-2 cell entry into the human lung cell Calu-3.³

Although camostat mesilate appears to be promising, another study has shown that the protease furin also plays an indispensable role in the cleavage of the SARS-CoV-2 spike protein.⁴ Unlike TMPRSS2, furin cleavage is not conserved across the coronavirus family, posing challenges for researchers looking to past research for guidance. Barile et al. tested camostat mesilate and used it to inhibit furin activity. Unfortunately, they discovered that camostat mesilate is a poor inhibitor of furin. The team suggested that future research should focus on developing a cocktail of inhibitors that can efficiently block both furin and TMPRSS2 activity.⁵

Host protease cleavage is critical to SARS-CoV-2 infection; therefore, focusing on the discovery of efficient protease inhibitors could effectively slow down transmission. More research needs to be conducted to determine protease inhibitors that can successfully inhibit the majority of proteases utilized by SARS-CoV-2. Trials on protease inhibitors are still in the early stages, but results show promise.

References

1. Zhu N., Zhang D., Wang W., Li X., Yang B., Song J., Zhao X., Huang B., Shi W., Lu R. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020;382:727–733.

• Kawase M., Shirato K., van der Hoek L., Taguchi F., Matsuyama S. Simultaneous treatment of human bronchial epithelial cells with serine and cysteine protease inhibitors prevents severe acute respiratory syndrome coronavirus entry. J. Virol. 2012; 86:6537–6545.

• Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N. H., Nitsche, A., Müller, M. A., Drosten, C., & Pöhlmann, S. (2020). SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell, 181(2), 271–280.e8. https://doi.org/10.1016/j.cell.2020.02.052

• Lukassen S., Chua R.L., Trefzer T., Kahn N.C., Schneider M.A., Muley T. SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. 2020;39

• Barile E., Baggio C., Gambini L., Shiryaev S.A., Strongin A.Y., Pellecchia M. (2020). Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming. Molecules. 25(10), 2424.

In the toolkit of strategies to stop the spread of COVID-19, many countries are reaching for smartphone apps¹. From Iceland to Israel, more than 30 contact-tracing systems are being developed by governments and health authorities. They promise to automate the laborious process of tracking down the contacts of infected individuals, helping to slow the spread of coronavirus through the population and save lives². Such apps can complement a country’s overall COVID-19 control strategies — including testing, contact tracing, isolation and social distancing — but they cannot serve as a replacement for them, or the thousands of contact-tracing teams they require. Like any health-care intervention, coronavirus apps need to conform to the highest standards of safety and efficacy. And yet, despite the pandemic’s global nature, countries are developing apps independently, and there are no global standards — which is rightly raising concerns².

COVID-19 apps have, to some extent, been inspired by the experiences of South Korea and Singapore — where electronic surveillance methods have helped to control infections. South Korea, in particular, is regarded as a model because it avoided severe lockdowns¹. The foundation for South Korea’s COVID-19 response is a comprehensive testing strategy, backed by a nationwide network of highly-trained contact-tracers. The strategy includes the use of phone alerts. When a person tests positive for COVID-19, a text alert is sent to everyone living nearby. This alert typically includes a link to a detailed log of the infected person’s movements — in some cases to the nearest minute. These movements are reconstructed from public data, such as closed-circuit television cameras.

It must be noted that the South Korean strategy is based on a degree of surveillance that people in many other countries would find hard to accept¹. The South Korean government is also permitted to access confidential records, such as credit-card transactions. The data are then stored centrally by government agencies. At the same time, people’s movements are anonymized and published online. As of July 16, some 6 months after the outbreak spread to South Korea, only a handful of new cases are being reported daily and only 291 deaths have been recorded in total³.

India is one of the few democracies that has made downloading its contact tracing app mandatory. Employees must use the app in order to get into offices or to travel. If they do not, they could face criminal prosecution. The Aarogya Setu app, meaning “healthcare bridge” in Hindi, has racked up more than 100 million downloads since launching on April 2 — a substantial number but only a small fraction of India’s population of 1.3 billion⁴. Using a phone’s Bluetooth and location data, Aarogya Setu lets users know if they have been near a person with Covid-19 by scanning a database of known cases of infection. While names and numbers of individuals won’t be made public, the app does collect this information, as well as gender, travel history, and if someone is a smoker. As Aarogya Setu stores location data and requires constant access to the phone’s Bluetooth, experts say that the app is invasive from a security and privacy viewpoint. Additionally, Aarogya Setu is not open source, which means that it cannot be audited for security flaws by independent coders and researchers⁵.

Apps with more limited scope have had some success. Police in Kerala, the first Indian state to report a coronavirus case, used the Covid Safety App to help enforce the quarantine of about 20,000 people in Kasargod, one of the worst-affected districts. Users voluntarily downloaded the app so police could track their location. The app had an SOS button that people could press if they needed essential goods or were in an emergency. As of April 15, Kerala had reported only four coronavirus deaths⁴.

While there have been successful attempts at mobile tracing technology in some countries, these efforts so far have fallen flat in the U.S. For example, the state of New Jersey is neither pursuing nor promoting exposure notification or digital alerting technology, according to Phil Murphy, the governor of the state⁶. New Jersey isn’t alone. Most states are giving the cold shoulder to smartphone apps. A survey of state health officials from Business Insider conducted the week of June 12th showed that only three states — Alabama, North Dakota and South Carolina — said they were going to use the software provided by Apple and Google. The number hasn’t grown since the same three states reported interest in May, and none have launched an app with the Google-Apple software⁶.

One serious concern with contact tracing apps is accuracy. Apps that link to official validated tests are obviously more likely to give accurate results. An alert based on self-diagnosis that turns out to be wrong — a false positive — could, of course, be corrected. But if incorrect information has been sent to a large group of contacts, it will have caused unnecessary alarm, and could have wrongly sent people into isolation for weeks.

An equally important concern is privacy. Researchers have shown that it is possible to re-identify individuals even when anonymized and aggregated data sets are incomplete. And then there’s the communications technology itself. Most apps share information using Bluetooth, a radio-frequency technology that allows devices to exchange information at close range. This is convenient, since most smartphones have it. But it has a history of security breaches that have been well-reported and studied. Smartphone users are usually advised to turn off Bluetooth when it is not needed, and especially when in close proximity to other phone users. But to work, COVID-19 apps need users to keep Bluetooth running — particularly when they are in public places¹.

Researchers and policymakers have worked hard over many decades to ensure that medicines, vaccines and health-care products conform to agreed standards of safety and efficacy. These often need to be global standards. COVID-19 smartphone apps are a health-care intervention, too, and will potentially affect hundreds of millions of lives. But they are being rolled out without pilot studies or risk assessments being published. Speed is, of course, of the essence — but so is due diligence and due process. This includes public dialogue; more involvement from researchers, including those who study ethics, law and public engagement; and a cast-iron commitment from governments that the information being harvested is secure and will only ever be used for the reasons it is being requested¹. 

References

1. Show evidence that apps for COVID-19 contact-tracing are secure and effective. (2020). Nature, 580(7805), 563–563. https://doi.org/10.1038/d41586-020-01264-1
2. Burgess, M. (2020, May 1). Coronavirus contact tracing apps were meant to save us. They won’t. WIRED. https://www.wired.co.uk/article/contact-tracing-apps-coronavirus.
3. COVID-19 CORONAVIRUS PANDEMIC. (n.d.). Retrieved March 22, 2020, from https://www.worldometers.info/coronavirus/
4. Findlay, S. (2020, May 18). Coronavirus contact-tracing apps struggle to make an impact. Financial Times. https://www.ft.com/content/21e438a6-32f2-43b9-b843-61b819a427aa.
5. Clarance, A. (2020, May 15). Aarogya Setu: Why India’s Covid-19 contact tracing app is controversial. BBC News. https://www.bbc.com/news/world-asia-india-52659520.
6. Ingram, D. (2020, June 12). Coronavirus contact tracing apps were tech’s chance to step up. They haven’t.NBCNews.com. https://www.nbcnews.com/tech/tech-news/coronavirus-contact-tracing-apps-were-tech-s-chance-step-they-n1230211.