Intraoperative Management of Hypertension

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Hypertension can dramatically increase surgical patients’ rates of morbidity and mortality. Preoperative hypertension increases a patient’s probability of experiencing cardiovascular complications during surgery by 35% [1]. Perioperative and postoperative hypertension can result in bleeding, myocardial infarctions, and adverse cerebrovascular events [2]. To manage intraoperative hypertension, clinicians must monitor patients’ blood pressure, while implementing regimens that account for the risk of cardiovascular events, possible blood pressure fluctuations, and preexisting medications [1].

 

Clinicians treating hypertensive surgical patients must avoid exacerbating preexisting hypertension, which requires a comprehensive understanding of high-risk events. Perioperatively, hypertension can occur or be worsened due to insufficient analgesia administration, anesthesia induction, extubation, volume overload, and clonidine withdrawal syndrome [1]. Patients undergoing intraperitoneal, abdominal aortic, peripheral vascular, or carotid surgery are most likely to experience hypertensive events [1]. Some studies have reported that anesthesia information management systems (AIMSs) are effective in managing hypertension intraoperatively, but this is not always true due to current technological limitations [3].

 

While lifestyle modifications may be preferable to pharmacology in driving long-term improvements, little can be done in that regard once surgery has begun [4]. Consequently, pharmacology is an essential aspect of perioperative hypertension management. Patients already taking antihypertensive medication should continue doing so, including on the day of surgery, if such drugs do not lead to negative interactions with drugs needed for surgery and anesthesia [1]. During surgery, clinicians should choose pharmacologic agents according to a patient’s comorbidities [5]. For example, patients with coronary artery disease may benefit most from beta-blockers, combined with diuretics or angiotensin-converting enzyme inhibitors [5]. Intraoperative use of beta-blockers can reduce patients’ 30-day and 1-year mortality [5]. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are not associated with higher mortality rates or complications following noncardiac surgery, suggesting that they are safe to continue administering in the surgical setting [5]. The goal of pharmacology therapy is to stabilize blood pressure at <130/80 mm Hg [5].

 

Depending on the anesthetic agents present during surgery, designing a safe and appropriate perioperative pharmacological regimen may become more difficult. Anesthesiologists should be aware of the anesthetic implications of each class of antihypertensive medication [6]. For instance, diuretics can promote dehydration, hypokalemia (if they are not potassium-sparing), and hyperkalemia (if they are potassium-sparing) [6]. Angiotensin II receptor antagonists can lead to refractory hypotension during induction and rebound hypertension once use has been discontinued [6]. Angiotensin-converting enzyme inhibitors (ACEIs) are more safely administered on the day of surgery if deep sedation is planned [6]. ACEIs may cause angioedema, but the risk is low [6].

 

If a patient experiences a hypertensive event during surgery, physicians should choose a fast-acting, safe, easily titrated, inexpensive, and predictable antihypertensive agent [2]. Clinicians should seek to gradually reduce blood pressure by 10 to 15% within the first hour [2]. Following that initial period, blood pressure should continue to decrease, the goal being to reach 160/100 mm Hg within the next two to six hours [2]. In these events, esmolol, nicardipine, fenoldopam, and labetalol are the most commonly used medications [2]. Parenteral agents can also be used, but newer medications appear safer during hypertensive emergencies [2]. While clonidine and ACE inhibitors are not easily titratable and have long-lasting effects, they may also be appropriate in urgent situations [2].

 

Ultimately, intraoperative hypertension requires clinicians to strike a delicate balance between various pharmacological considerations. Because hypertension increases mortality and morbidity, physicians should aim to design the optimal plan for each individual patient.

 

References 

 

[1] M. Koutsaki et al., “Evaluation, risk stratification and management of hypertensive patients in the perioperative period,” European Journal of Internal Medicine, vol. 69, p. 1-7, November 2019. [Online]. Available: https://doi.org/10.1016/j.ejim.2019.09.012.  

 

[2] J. Varon and P. E. Marik, “Perioperative hypertension management,” Vascular Health and Risk Management, vol. 4, no. 3, p. 615-627, June 2008. [Online]. Available: https://doi.org/10.2147/vhrm.s2471.  

 

[3] B. G. Nair et al., “Anesthesia Information Management System-Based Near Real-Time Decision Support to Manage Intraoperative Hypotension and Hypertension,” Anesthesia & Analgesia, vol. 118, no. 1, p. 206-214, January 2014. [Online]. Available: https://doi.org/10.1213/ANE.0000000000000027.  

 

[4] R. Oza and M. Garcellano, “Nonpharmacologic Management of Hypertension: What Works?,” American Family Physician, vol. 91, no. 11, p. 772-776, June 2015. [Online]. Available: https://www.aafp.org/afp/2015/0601/afp20150601p772.pdf.  

 

[5] W. S. Aronow, “Management of hypertension in patients undergoing surgery,” Annals of Translational Medicine, vol. 5, no. 10, p. 227, May 2017. [Online]. Available: https://doi.org/10.21037/atm.2017.03.54. 

 

[6] R. Yancey, “Anesthetic Management of the Hypertensive Patient: Part 1,” Anesthesia Progress, vol. 65, no. 2, p. 131-138, Summer 2018. [Online]. Available: https://doi.org/10.2344/anpr-65-02-12.  

 

Comparison of Global COVID Vaccine Rollout

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In order to adequately respond to the global nature of the COVID-19 pandemic, governments in most countries are working to rapidly vaccinate their residents. Some countries have been successful, though COVID vaccine rollout has been plagued by unequal access. Others have sufficient supply but have struggled with distribution. Meanwhile, low- and middle-income countries have faced difficulties obtaining doses, causing governments and bodies such as the World Health Organization (WHO) to respond.

 

As of January, Israel had begun to vaccinate citizens at the fastest pace of any nation. The Council on Foreign Relations reported that within two weeks of launching its campaign, Israel had vaccinated 15% of its population [1]. By early February, nearly 90% of the country’s over-60 population had been immunized. These efforts provided a framework for a successful vaccination campaign: between mid-January and early February, the 60+ age cohort saw a 41% decrease in infections and a 31% decrease in hospitalizations [2]. However, in late February, when roughly 50% of Israel’s population had received at least one dose of vaccine, an estimated 0.8% of the Palestinian population in the West Bank and Gaza had access to a dose [3]. The United Arab Emirates shares several advantages with Israel — namely a small population and universal healthcare system — enabling smooth immunizations. By mid-January, the Emirates had delivered vaccine doses to roughly 20% of its residents [1]. The United Kingdom has also had success: in mid-February, 12 million people had received a dose, a number comparable to Israel’s entire population. Nearly every person in the United Kingdom now lives within ten miles of a vaccination center, with those in extremely remote areas able to visit mobile vaccination sites [4].

 

Other higher-income countries have struggled with logistics and access despite the ability to purchase supplies. As of February 11, the Biden administration had purchased 600 million doses of vaccine from Pfizer and Moderna [5], but the United States and several other Western countries still face vaccine hesitancy rates in excess of 50% [6]. In Canada, a network of local and national systems has been responsible for distribution. In late January, 75% of doses distributed to provincial and territorial governments had yet to be administered to individuals [7].

 

Meanwhile, in lower-income countries, the sheer expense of vaccines has proven to be a challenge. As of February, over 75% of vaccines had been administered in just 10 countries, according to the WHO and UNICEF [8]. Meanwhile, lower and middle-income countries comprise 85% of the worldwide population [9]. Both governments and NGOs have responded to this inequality. COVAX, an initiative led by WHO, UNICEF, GAVI, and other bodies, has set a goal of delivering 2 billion doses in 2021, with at least 1.3 billion in low- or middle-income countries. Governments in higher-income countries have contributed to the effort, with the U.S. pledging $4 billion to COVAX over two years. However, low- and middle-income countries cannot vaccinate more than 20% of their populations through COVAX, indicating that inequality will remain a problem [8]. The World Bank has pledged $12 billion for vaccine rollout efforts in the developing world and both Russia and China have distributed vaccine supplies to countries across Asia and the Middle East [10].

 

Global comparisons indicate that a range of logistical, geographical, and political barriers must be overcome to achieve widespread vaccination. These barriers differ from country to country, rooted in various healthcare systems, ethnic conflicts, cultural attitudes, and financial inequity.

 

References 

 

[1] Felter, Claire. What to Know About the Global COVID-19 Vaccine Rollout So Far. Council on Foreign Relations, 2021, www.jstor.org/stable/resrep29866.  

[2] Mallapaty, Smriti. “Vaccines Are Curbing COVID: Data from Israel Show Drop in Infections.” Nature, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/33547434/.  

[3] Kennes, Matthias. Opinion, 22 February 2021. “The Stark Inequality of COVID-19 Vaccination between Israel and Palestine: MSF.” Médecins Sans Frontières (MSF) International, 31 Mar. 2021, www.msf.org/stark-inequality-covid-19-vaccination-between-israel-and-palestine. 

[4]  Baraniuk, Chris. “Covid-19: How the UK Vaccine Rollout Delivered Success, so Far.” BMJ, 2021, doi:10.1136/bmj.n421 

[5] Division, News. “Biden Administration Purchases Additional Doses of COVID-19 Vaccines from Pfizer and Moderna.” HHS.gov, 12 Feb. 2021, www.hhs.gov/about/news/2021/02/11/biden-administration-purchases-additional-doses-covid-19-vaccines-from-pfizer-and-moderna.html.  

[6] Sallam, Malik. “COVID-19 Vaccine Hesitancy Worldwide: A Concise Systematic Review of Vaccine Acceptance Rates.” Vaccines, vol. 9, no. 2, 2021, p. 160., doi:10.3390/vaccines9020160 

[7] Marchildon, Gregory P. “The Rollout of the COVID-19 Vaccination: What Can Canada Learn from Israel?” Israel Journal of Health Policy Research, vol. 10, no. 1, 2021, doi:10.1186/s13584-021-00449-x 

[8]B urki, Talha Khan. “Challenges in the rollout of COVID-19 vaccines worldwide.” The Lancet. Respiratory medicine vol. 9,4 (2021): e42-e43. doi:10.1016/S2213-2600(21)00129-6. 

[9] Wouters, Olivier J, et al. “Challenges in Ensuring Global Access to COVID-19 Vaccines: Production, Affordability, Allocation, and Deployment.” The Lancet, vol. 397, no. 10278, 2021, pp. 1023–1034., doi:10.1016/s0140-6736(21)00306-8 

[10] “World Bank COVID-19 Response.” World Bank, www.worldbank.org/en/news/factsheet/2020/10/14/world-bank-covid-19-response.  

The Effect of General Anesthesia on the Hippocampus

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While general anesthesia (GA) can safely and reversibly induce unconsciousness, exposure to GA may, as has grown increasingly evident, give rise to cellular and structural changes throughout the brain and hippocampus, incurring both neurotoxic and neuroprotective effects (1). Some of these effects may be long-lasting and may translate into cognitive and behavioral deficits, given the key role of the hippocampus in memory and cognition, as well as the fact that postnatal hippocampal neurogenesis persists into adulthood (2). As such, the United States Food and Drug Administration issued in 2016 a precautionary communication on GA use in patients under 3 years of age (3).

The effects of GA span a range of intra- and intercellular scales. During a critical period of brain development, midazolam, a pre-anesthetic, not only increases the rate of formation of dendritic spines but also the stability of newly formed spines. These two mechanisms together lead to a sustained increase in dendritic spine densities forming fully functional synapses (4).

In general, general anesthesia may impair neuronal maturation and survival in the hippocampus, as well as neurogenesis. One study found that propofol, which can be used as an induction agent during general anesthesia, impairs the maturation and survival of adult-born hippocampal neurons (4), while another study highlighted a certain age sensitivity of cells to these impacts, as propofol induced a marked decrease in the survival and dendritic maturation of 17-day-old, but not 11-day-old, hippocampal neurons at the time of anesthesia (5). This cell age-dependent vulnerability of neurons to anesthetic toxicity has since been replicated (6). Impaired neurogenesis and cellular function have also been demonstrated to be drug- and sex-specific. One study found that isoflurane, specifically, induced hippocampal cell injury and cognitive impairments in adult rats (7), while another demonstrated that propofol produces short-lived impairments, while midazolam and dexmedetomidine alter cognition after a several-week delay through mechanisms associated with decreased neurogenesis (8). Behaviorally, GA administered to postnatal day 6 (P6) rhesus monkeys was found also to result in increased anxiety and emotional reactivity when they reached 6 months of age; this also impaired hippocampus-related learning tasks in adulthood (9).

At a molecular level, general anesthesia induces neuroinflammation – including in the hippocampus. Specifically, one research study showed the GA-activated canonical nuclear factor-κB pathway to be linked to increased isoflurane-induced hippocampal interleukin-1β levels and resultant cognitive deficits in aged rats (10), while another research team demonstrated hippocampal and extra-hippocampal dysfunction due to neuroinflammation following GA (11). These effects appear anesthetic-specific (12).

A range of additional intracellular effects have also been identified. First, the exposure of P7 rat pups to 6-hour anesthesia has been shown to induce aberrant mitochondrial morphology in neurons and a marked reduction in the number of mitochondrion-containing presynaptic terminals in the hippocampal subiculum (13,14). In addition, hippocampal tau protein phosphorylation has been linked to isoflurane-induced cognitive dysfunction in mice (15). Finally, at a cytoarchitectural level, one study found long-erm effects of single or multiple sevoflurane exposures on rat hippocampal ultrastructure (16).

General anesthesia has ostensibly different impacts on the hippocampus in anesthetic-, brain developmental stage-, and age-specific ways. Clearly, further laboratory work and clinical investigations are warranted to ensure the prevention of any lasting adverse effects on the human brain and hippocampal function in particular.

 

References

 

1. Wu L, Zhao H, Weng H, Ma D. Lasting effects of general anesthetics on the brain in the young and elderly: “mixed picture” of neurotoxicity, neuroprotection and cognitive impairment. Vol. 33, Journal of Anesthesia. Springer Tokyo; 2019. p. 321–35.

2. Deng W, Aimone JB, Gage FH. New neurons and new memories: How does adult hippocampal neurogenesis affect learning and memory? Nature Reviews Neuroscience. 2010.

3. FDA. FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women. US Food Drug Adm Drug Saf Commun. 2016. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-review-results-new-warnings-about-using-general-anesthetics-and

4. De Roo M, Klauser P, Briner A, Nikonenko I, Mendez P, Dayer A, et al. Anesthetics rapidly promote synaptogenesis during a critical period of brain development. PLoS One. 2009.

5. Krzisch M, Sultan S, Sandell J, Demeter K, Vutskits L, Toni N. Propofol anesthesia impairs the maturation and survival of adult-born hippocampal neurons. Anesthesiology. 2013 Mar;118(3):602–10.

6. Hofacer RD, Deng M, Ward CG, Joseph B, Hughes EA, Jiang C, et al. Cell age-specific vulnerability of neurons to anesthetic toxicity. Ann Neurol. 2013.

7. Lin D, Zuo Z. Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats. Neuropharmacology. 2011 Dec;61(8):1354–9.

8. Kim JL, Bulthuis NE, Cameron HA. The Effects of Anesthesia on Adult Hippocampal Neurogenesis. Front Neurosci. 2020 Oct 22;14:1090.

9. Raper J, Alvarado MC, Murphy KL, Baxter MG. Multiple anesthetic exposure in infant monkeys alters emotional reactivity to an acute stressor. Anesthesiology. 2015;123(5):1084–92.

10. Li ZQ, Rong XY, Liu YJ, Ni C, Tian XS, Mo N, et al. Activation of the canonical nuclear factor-κB pathway is involved in isoflurane-induced hippocampal interleukin-1β elevation and the resultant cognitive deficits in aged rats. Biochem Biophys Res Commun. 2013 Sep 6;438(4):628–34.

11. Cascella M, Bimonte S. The role of general anesthetics and the mechanisms of hippocampal and extra-hippocampal dysfunctions in the genesis of postoperative cognitive dysfunction. Vol. 12, Neural Regeneration Research. Wolters Kluwer Medknow Publications; 2017. p. 1780–5.

12. Shen X, Dong Y, Xu Z, Wang H, Miao C, Soriano SG, et al. Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment. Anesthesiology. 2013.

13. Sanchez V, Feinstein SD, Lunardi N, Joksovic PM, Boscolo A, Todorovic SM, et al. General anesthesia causes long-term impairment of mitochondrial morphogenesis and synaptic transmission in developing rat brain. Anesthesiology. 2011.

14. Lunardi N, Ori C, Erisir A, Jevtovic-Todorovic V. General anesthesia causes long-lasting disturbances in the ultrastructural properties of developing synapses in young rats. Neurotox Res. 2010.

15. Li C, Liu S, Xing Y, Tao F. The role of Hippocampal Tau protein phosphorylation in isoflurane-induced cognitive dysfunction in transgenic APP695 Mice. Anesth Analg. 2014.

16. Amrock LG, Starner ML, Murphy KL, Baxter MG. Long-term effects of single or multiple neonatal sevoflurane exposures on rat hippocampal ultrastructure. In: Anesthesiology. Lippincott Williams and Wilkins; 2015. p. 87–95.

Human Challenge Studies in Clinical Research

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Human challenge studies are research experiments involving the deliberate exposure, or “challenge” of human subjects to infectious diseaseregardless of whether they have been vaccinated [1]. Indeed, a human challenge study can involve observing the results of certain treatments, including vaccines, as well as the course of the infection itself.  

 

Human challenge studies have been part of medical research and the development of treatments since the eighteenth century. It is widely accepted that the first modern human challenge study was conducted by Edward Jenner in 1796 [2]. At the time, smallpox was widespread and virulent. Variolation, wherein a subject would be deliberately exposed to smallpox in an attempt to inoculate them, had a high incidence rate. Jenner’s experiment involved exposure to cowpox, a milder disease, through rubbing the infection onto incisions in the skin, and proved successful. Contemporary researchers acknowledge that Jenner’s experiment was ethically dubious, in part because his first subject was a child and therefore could not give informed consent [2]. However, these studies have remained part of medical research ever since. Discussion surrounding the efficacy and ethics of these studies has surfaced during major pandemics, including the most recent COVID-19 pandemic.  

 

The persistence of human challenge studies is in part due to the establishment of certain ethical standards in medical research that has allowed for the minimization of risk. However, the extent to which these studies are ethically acceptable continues to be debated. Bambery et al. list several criteria that are already standard for medical research, including risk reduction, informed consent, and attention to how participants are selected [3]. In addition, the authors propose criteria for performing human challenge studies, including independent review of the challenge model, assessment of risks and benefits that is accessible to the public, protective measures to prevent those outside of the study from being exposed, and compensation to participants for harm incurred [3].  

 

When it comes to pandemics, these studies can improve the speed and efficacy with which vaccines are approved. It also requires far fewer subjects to be exposed to potentially harmful vaccine candidates than in a traditional phase 3 trial [4]. Eyal et al. argues that the pressing nature of the COVID-19 pandemic made human challenge studies permissible, assuming they follow an appropriate design [4].  

 

However, this model does not entirely assuage concerns regarding public perception and risk to participants [5]. High risk of exposure to COVID-19 is correlated with vulnerabilities such as poverty. Given the history of exploitation connected to human challenge studies, targeting populations that have been subjected to injustice for recruitment as test subjects could reflect badly on the project and sow mistrust in the communities that researchers rely on to collect data [6]. And while Eyal et al. emphasize that volunteers should receive priority care, it is not guaranteed that treatment for damage done to participants’ health in potential studies will be fully compensated [6].  

 

In February, the government of the United Kingdom received approval to launch the first human challenge study involving SARS-COV-2. The study will involve first infecting patients and observing them in quarantine, and later it will involve the testing of vaccine candidates [1]. Researchers are still recruiting participants for this study. How the researchers will handle the ethical dilemmas mentioned above as they arise remains to be seen, but, if successful, the study could improve our understanding of the virus and accelerate the arrival of approved vaccines to the market.        

 

References 

 

[1] Newman, Tim | Medical News Today | Feb 18, 2021. “What Are Human Challenge Studies?” Medical News Today, 18 Feb. 2021, https://www.medicalnewstoday.com/articles/what-are- human-challenge-studies 

 

[2] Machemer, Theresa | Smithsonian Magazine | Dec 16, 2020. “A Brief History of Human Challenge Trials” Smithsonian Magazine, 16 Dec. 2020, https://www.smithsonianmag.com/science-nature/brief-history-human-challenge-trials-180976556/ 

 

[3] Bambery, B. et al. “Ethical Criteria for Human Challenge Studies in Infectious Diseases: Table 1.” Public Health Ethics, vol. 9, no. 1., 2015, pp. 92-103. Doi: 10.1093/phe/phv026. 

 

[4] Eyal, N., et al. “Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure.” The Journal of Infectious Diseases, 2020. Doi: 10.1093/infdis/jiaa152. 

 

[5] “Human Challenge Studies Are Unlikely to Accelerate Coronavirus Vaccine Licensure Due to Ethical and Practical Issues.” The Journal of Infectious Diseases, 2020. Doi: 1093/infdis/jiaa457.  

 

[6] Euzebiusz, J. & Michael J. Selgelid. “COVID-19 Human Challenge Studies: Ethical Issues.” Lancet Infectious Diseases, 2020. Doi: 10.1016/S1473-3099(20)30438-2. 

Anesthesia Management of Endovascular Therapy 

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Endovascular therapy (EVT) is the preferred method of treating acute ischemic stroke (AIS) [1]. The operation requires a high degree of patient cooperation, which can be difficult to achieve, given that AIS patients may have difficulty communicating [2]. Fortunately, using anesthesia during the procedure is an option. 

 

Past research indicates that general anesthesia for EVT leads to worse patient outcomes than conscious sedation (CS) [1, 2, 3]. Three separate studies found that patients who experienced lower levels of sedation during EVT exhibited lower mortality, better outcomes, and higher reperfusion rates [2]. Conversely, the study found that “heavy sedation…was an independent predictor of death” [2]. The reason for GA’s worse patient outcomes is unknown. One possibility is the effect of procedural delay: it takes more time for anesthesiologists to administer GA than CS [2]. Other potential explanations include GA’s association with hemodynamic instability, neurotoxicity, hypertension, and prolonged intubation [2]. 

 

Despite this evidence, many researchers have recently pointed out design flaws in these studies, calling into question whether GA is riskier than CS. For one, none of the aforementioned reports are randomized or prospective [1]. Each is retrospective, which could lend itself to bias concerning which studies were chosen and who their subjects were [1]. Furthermore, other experiments have encountered evidence to the contrary. Langner et al. conducted a retrospective study of all EVT patients in Germany over five years [4]. They did not find any significant difference in outcome between GA and CS patients [4]. Similarly, Wang et al. found that GA patients did not experience worse outcomes when compared to historical subgroups [5]. Further research is needed to determine which approach to anesthesia management of EVT is safer. 

 

Being aware of best practices can help anesthesiologists avoid adverse events associated with general anesthesia. The decision to administer GA should be based on a careful assessment of the patient’s neurological and medical status [6]. Many anesthesiologists reserve GA for patients suffering from compromised airways, bulbar dysfunction, or other complex situations, in addition to patients having major surgeries [2]. With EVT, GA may not be appropriate when delay, a lack of institutional resources, or a high risk of propagating cerebral ischemia would compromise surgical success [7]. 

 

Before the operation, anesthesiologists should identify preemptive strategies to avoid complications [8]. To avoid hypotension, anesthesiologists should consider administering vasopressor therapy and applying invasive monitoring [8]. Anesthesiologists should also communicate with the neurological team to establish hemodynamic parameters [2]. The team should also plan to extubate at the end of the surgery in the absence of contraindications [2]. 

 

During EVT, anesthesiologists must closely attend to patients’ vitals. Because GA can lower BP, anesthesiologists must monitor BP throughout the operation to mitigate any hypotensive events [8]. Ventilation and oxygenation are also of concern [9]. Because researchers have not identified the optimal ranges of either measure, anesthesiologists must observe both to prevent hypoxemia and cerebral vasoconstriction [9]. Higher end-tidal carbon dioxide levels and sustained normocapnia are associated with better outcomes, so maintaining both is recommended [9]. 

 

Unfortunately, the optimal approach to administering general anesthesia to patients receiving endovascular therapy is still being investigated. Regardless, following these best practices and being conscious of the ever-evolving literature on this topic are helpful first steps for promoting the best possible EVT outcomes. 

 

References 

 

[1] C. Z. Simonsen et al., Anesthetic strategy during endovascular therapy: General anesthesia or conscious sedation? (GOLIATH – General or Local Anesthesia in Intra Arterial Therapy) A single-center randomized trial,International Journal of Stroke, vol. 11, no. 9, p. 1045-1052, July 2016. [Online]. Available: https://doi.org/10.1177/1747493016660103. 

 

[2] M. T. Froehler et al., Anesthesia for endovascular treatment of acute ischemic stroke,Neurology, vol. 79, no. 13, p. S167-S173, September 2012. [Online]. Available: https://doi.org/10.1212/WNL.0b013e31826959c2. 

 

[3] A. Abou-Chebl et al., Conscious Sedation Versus General Anesthesia During Endovascular Therapy for Acute Anterior Circulation Stroke,” Stroke, vol. 41, p. 1175-1179, April 2010. [Online]. Available: https://doi.org/10.1161/STROKEAHA.109.574129. 

 

[4] S. Langner et al., [Endovascular treatment of acute ischemic stroke under conscious sedation compared to general anesthesia – safety, feasibility and clinical and radiological outcome].,” Fortschritte auf dem Gebiete der Rontgenstrahlen und der Nuklearmedizin, vol. 185, no. 4, p. 320-327, February 2013. [Online]. Available: https://doi.org/10.1055/s-0032-1330361. 

 

[5] A. Wang et al., General Anesthesia During Endovascular Stroke Therapy Does Not Negatively Impact Outcome,” World Neurosurgery, vol. 99, p. 638-643, March 2017. [Online]. Available: https://doi.org/10.1016/j.wneu.2016.12.064. 

 

[6] D. Sharma et al., Anesthetic Management of Endovascular Treatment of Acute Ischemic Stroke During COVID-19 Pandemic: Consensus Statement From Society for Neuroscience in Anesthesiology & Critical Care (SNACC),” Journal of Neurosurgical Anesthesiology, vol. 32, no. 3, p. 193-201, July 2020. [Online]. Available: https://doi.org/10.1097/ANA.0000000000000688.  

 

[7] D. L. McDonagh et al., Anesthesia and sedation practices among neurointerventionalists during acute ischemic stroke endovascular therapy,” Frontiers in Neurology, vol. 1, no. 118, November 2010. [Online]. Available: https://doi.org/10.3389/fneur.2010.00118. 

 

[8] M. J. Davis et al., Anesthetic Management and Outcome in Patients during Endovascular Therapy for Acute Stroke,” Anesthesiology, vol. 116, p. 396-405, February 2012. [Online]. Available: https://doi.org/10.1097/ALN.0b013e318242a5d2. 

 

[9] L. K. Rasmussen, C. Z. Simonsen, and M. Rasmussen, Anesthesia practice for endovascular therapy of acute ischemic stroke in Europe,” Current Opinion in Anaesthesiology, vol. 32, no. 4, p. 523-530, August 2019. [Online]. Available: https://doi.org/10.1097/ACO.0000000000000746.