Expanesthetics: Anesthesia Research Meets Venture Capitalism

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Expanesthetics is an expanding startup dedicated to an ambitious goal: to discover new inhalational anesthetic agents that have “improved qualities and a reduced side effect profile.” It aims no higher than to revolutionize the field of inhaled anesthetics, with potentially the same effect as the fluorinated hydrocarbons had in the 1940s when they largely eclipsed older anesthetics such as ether or chloroform. It’s an attractive and somewhat unique sales pitch, and the company claims to be the only one of its kind to be investing in research and development for the next generation of inhaled anesthetics.

How exactly Expanesthetics plans to accomplish this formidable goal is outlined in general terms on their website: to utilize a patent-pending screening platform to identify molecules with potential anesthetic and analgesic properties, and to test these molecules for potential utility as general anesthetics. It purports to have access to licensed and proprietary libraries of molecules from which to conduct the screens. The exact nature of the screening platform and its parameters for identifying promising molecules is not stated outright, which is understandable since it is the basis of their enterprise. The mechanism of action of modern inhaled anesthetics in general is one of the great unsolved questions of the past half century, and if Expanesthetics has indeed made a breakthrough into what makes them tick, the potential applications are not to be underestimated.

anesthesia

Expanesthetics is the brainchild of Dr. Robert Brosnan, a professor in the Department of Surgical and Radiological Sciences at the UC Davis School of Veterinary Sciences. According to Brosnan, his laboratory discovered a “plausible molecular mechanism of action” for current anesthetic agents, allowing him make predictions on novel agents and their interactions with specific receptors. A search of PubMed for Brosnan yields collection of anesthetic molecular and animal-based research, the most recent of which describes the anesthetic synergy between N-butane and n-pentane. It’s solid research, detailed, rigorous and transparent. Whether it has any relation to Brosnan’s discovery that prompted him to start Expanesthetics is unclear.

One challenge Expanesthetics has put forward is the question, “is what we have good enough?” In other words, why revolutionize a field that isn’t broken? In the arena of research and development, this question doesn’t really seem to have a place. Horses must have seemed just fine before the first cars came along, and what anesthesiologist has not lamented the vasodilatory properties of our current inhaled anesthetics when pushing pressors after induction? It remains to be seen what fruits will yield from this ambitious startup, but raising nearly $20 million in the name of anesthesia research is an impressive feat worth keeping an eye on.

References:

https://expanesthetics.com/

https://gsm.ucdavis.edu/Expanesthetics

Postoperative Pain Management After Cesarean Delivery

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Cesarean delivery, the most commonly performed major surgery in the United States, is often conducted under neuraxial anesthesia, however epidurals are routinely removed immediately postoperatively and spinals wear off within hours. Effective perioperative pain management relies on a multimodal approach to avoid complications such as delayed functional recovery, impaired maternal-fetal bonding, increased postpartum depression, and persistent chronic pain – all associated with poor perioperative pain control. Incisional and pelvic pain may persist beyond 6 months after surgery in up to 18% of patients, at incidences higher than associated with vaginal deliveries but lower than non-obstetric surgeries.

Neuraxial anesthesia is preferable to general anesthesia in regards to prevention of persistent pain after cesarean birth, unsurprising as severe acute postoperative pain is one of the strongest predictors of the development of chronic pain. Single shot spinal anesthetics are the most common method, with epidural and combined spinal-epidural anesthetics as alternatives.  While continuing epidural analgesia after the immediate postoperative period may be a viable option for high-risk patients (i.e. those with preexisting chronic pain), routine use risks increased thromboembolic events due to decreased mobility, increases costs, and burdens nursing staff.

Neuraxial (intrathecal or epidural) morphine has a longer half-life than more lipophilic opiates such as fentanyl, with a duration of action from 14 to 36 hours. The optimal dose is unclear, with escalating doses (>100mcg) leading to increased side effects such as nausea, vomiting and pruritus. Respiratory depression can occur, but was not observed in studies reviewed in a 2016 meta-analysis. Even in women with risk factors for respiratory depression (e.g. obstructive sleep apnea), neuraxial opiates are still recommended over IV opiate administration.

Scheduled non-steroidal anti-inflammatory medications and acetaminophen is recommended in all patients undergoing cesarean delivery unless contraindicated (e.g. postpartum hemorrhage would preclude the use of NSAIDs). NSAIDs decrease opiate use by 30-50%, and acetaminophen by 20%.

Wound infiltration of local anesthetics can reduce pain scores and opiate use for up to 48 hours postoperatively, with continuous infusion via subfascial catheters placed intraoperatively being more effective than single dose techniques. These catheters offer more mobility than epidural catheters, but only treat somatic and not visceral pain.

Transversus abdominis plane blocks are another option for somatic pain, significantly improving postoperative pain and reducing opiate consumption in patients under general anesthesia or when neuraxial morphine was not used. It is also a viable rescue technique in severe acute postoperative pain. The duration of effect of single shot TAP blocks is 6-12 hours.

Postoperative pain control after cesarean delivery should be a priority, with a multimodal approach being recommended to reduce maternal and fetal exposure to opiate medications and prevent the development of persistent postoperative pain.

References:

Carvalho BButwick AJ. Postcesarean Delivery Analgesia. Best Pract Res Clin Anaesthesiol. 2017 Mar;31(1):69-79. doi: 10.1016/j.bpa.2017.01.003.

Anesthesia for Tonsillectomy

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Tonsillectomy and adenoidectomy is one of the most common surgical procedures in children, and is sometimes performed in adults. Its unique constellation of patient population, surgical considerations, and anesthetic complications leads to an increased risk of morbidity and mortality that can be significantly influenced by anesthetic technique. Debate over many aspects of anesthetic management of these cases still continues.

Many indications exist for removing the tonsils and adenoids, including upper airway obstruction, dysphagia, sleep disorders such as obstructive sleep apnea (OSA), peritonsillar abscess unresponsive to medical management, febrile seizures due to tonsillitis and tonsillar biopsy.

OSA is increasingly becoming a common indication for tonsillectomy in children. Children with OSA may present with insidious symptoms such as failure to thrive, behavior problems, and poor school performance. Symptomatology often does not correlate with disease severity. This patient population is at risk for postoperative apnea and hypoxia, which in children could quickly deteriorate to cardiac arrest if not corrected. Some anesthesiologists choose to avoid long acting narcotics in these patients, however adequate postoperative pain control must be ensured to prevent other complications common in this surgical procedure such as postoperative nausea and vomiting (PONV) and emergence delirium. Multimodal analgesia is recommended with a combination of opiates, acetaminophen, and NSAIDs. Toradol is associated with increased postoperative bleeding according to a Cochrane analysis and is thus avoided, but there is insufficient data that other NSAIDs carry this same association. Surgeon-administered local anesthesia to the lesser palatine and glossopharyngeal nerves is an excellent adjunct for pain control in addition to general anesthesia, and also has the benefit of a smoother extubation.

 

Tonsil

 

 

Postoperative nausea and vomiting is a significant concern in this population, as retching can cause rebleeding of the surgical site. Dexamethasone and ondansetron are routinely administered for prophylaxis. Liberal IV hydration has also showed promise in preventing PONV, with a bolus of 10-30ml/kg/hr in older children resulting in significantly decreased symptoms.

Airway management warrants special consideration, as the airway must be shared between the anesthesiologist and surgeon. An endotracheal tube (ETT) is the gold standard, typically an oral RAE or reinforced ETT taped down the midline. However reinforced laryngeal mask airways (LMA) have been described in the literature. The use of LMAs should be limited to practitioners who are experienced in their use for tonsillectomies, as they carry an increased risk of laryngospasm and aspiration. Advocates argue that they allow for a smoother emergence and avoidance of neuromuscular blockade.

Extubation may be carried out deep or awake. The conservative approach is to remove the ETT when the patient is awake, to decrease the risk of laryngospasm, aspiration, and post-extubation apnea. However deep extubations afford smoother emerge and decreased emergence delirium. There have not been significant differences in complications between the two methods that have been borne out in the literature. Dexmedetomidine is a useful adjunct for decreasing emergence delirium in the pediatric population.

Post-tonsillectomy bleeding is a major complication of this procedure, and must be promptly recognized and managed. Establishment of large bore IV access, ready availability of suctioning, rapid sequence induction and resuscitation with blood products are crucial to avoiding mortality and morbidity.

Enhanced Recovery After Surgery

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The Enhanced Recovery After Surgery (ERAS) protocol was initiated in the 1990s and describes a multimodal, interdisciplinary, and evidence-based approach to perioperative management for major surgeries. The protocol aims to reduce post-operative complications and hospital stay duration, earlier return of bowel function, earlier return of normal activities, and improvement in cardiopulmonary function.

The body undergoes profound stress during and after surgery, and ERAS attempts to disrupt medical stressors by addressing preoperative counseling, optimizing nutrition, standardizing analgesic and anesthetic regimens, and early mobilization. Many of these goals are achieved through management by the anesthesiologist or CRNA. Preoperatively, the patient remains hydrated with minimized fasting periods and carbohydrate loading to maintain euglycemia. Intraoperatively, the anesthesiologist maintains normothermia with warmed fluids and warming blanket, utilizes goal-directed fluid therapy, closely controls blood glucose levels within a specific range, and utilizes lung protective ventilation. Opioids are minimized or avoided completely. Post operatively, nausea is avoided with prophylactic medications like dexamethasone and ondansetron. Oral intake and nutrition is encouraged, and ambulation and gut motility are supported by adhering to an opioid free pain regimen.

Multimodal analgesia is an important component of ERAS, as recovery can be delayed by inadequate analgesia. First-line analgesia often relies on large doses of opioids, which can contribute to sedation, nausea, constipation, and delaying return to normal activity and resumption of bowel function. By using two or more analgesic agents or techniques simultaneously, better pain relief can be achieved. Minimizing opioids can be accomplished with regional anesthesia such as peripheral nerve blocks or epidurals, non-opioid analgesics like COX-2 inhibitors or NSAIDs, intravenous or oral acetaminophen, anticonvulsants, and infusions of ketamine or lidocaine.

There are many benefits of the ERAS protocol. There are a multitude of reports in literature describing improvement in surgical outcomes including reduction in postoperative complication rates and opioid prescribing rates. There has been a decrease in hospital mortality among colorectal surgery patients as well as reduction in delirium, blood clots, muscle atrophy, infection, and nausea. In addition, patient satisfaction is increased, and cost effectiveness has been demonstrated in numerous studies around the world. The considerable costs of implementing an ERAS program is easily offset by the potential savings of thousands of dollars per surgery. As the benefits of ERAS become better known and accepted, healthcare providers should expect ERAS and multimodal analgesia to become more prevalent in the perioperative setting.

 

Anesthesiology Clinicians Poised to Enter Executive Leadership

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On September 5th, 2017, Dr. Jerome Adams was sworn in as the 20th Surgeon General of the United States, marking an important moment in the movement for anesthesia clinicians as emerging prominent leaders in the U.S.[1]

Dr. Adams’ career trajectory is an essential combination of academic prestige, private and public sector experience, and emerging leadership roles.[2] Dr. Adams received his medical degree from the Indiana University School of Medicine and Master’s in Public Health from the University of California, Berkeley. Although he began in private practice, Dr. Adams swiftly moved into academia and public service, working as an Assistant Professor at his alma mater while writing frequently on topics pertinent to the pain management field. Dr. Adams then received his first major leadership role when he was nominated as the Indiana State Health Commissioner, setting the stage for his future nomination to the national stage. In his role as Surgeon General, Dr. Adams represents the first anesthesiologist to hold the position, which in the past has taken candidates from a pool of pediatricians, internists, and registered nurses (RNs). Dr. Adams has publicly stated that with this new leadership position, he aims to focus on issues that sit at the center of his specialty and U.S. healthcare needs, e.g. the national opioid crisis. As a leading national expert on substance abuse, and a practicing physician, Dr. Adams holds an impressive wealth of knowledge that will serve him well as the new acting Surgeon General.

Surgeon General is merely one of the leadership roles that physicians, and increasingly anesthesiologists, are aiming to occupy. CEOs of hospital networks, heads of anesthesia management companies, medical leads at insurance companies…The possibilities are nearly endless when it comes to clinician executive leadership, and anesthesiology-related professionals have a high chance of capturing these opportunities.

General Surgeon

To begin, anesthesia professionals, such as anesthesiologists and CRNAs, have extensive experience in participating and managing complex teams. As Thomas H. Lee, M.D., writes in the Harvard Business Review, “More often, institutional leaders must move groups …to bring physicians from different disciplines but the same patient population closer to one another.” [3] In this regard, anesthesiologists and CRNAs have a built-in advantage towards leading effective team alignment strategies: As anesthesiology-based clinicians must routinely work with an array of physicians and nurses from other departments to provide holistic care, they understand the process and purpose of non-siloed management. This enhances the capability for strong leadership in a complex healthcare setting, both on the clinical and business side of organizational management.

Moreover, the need for physicians in healthcare-centered executive roles is rising, paving the way for anesthesiologists and CRNAs to acquire new opportunities in leadership. In 2011, a study was released in Social Science and Medicine citing that quality scores were approximately 25 percent higher in hospitals with physician CEOs as compared to hospitals led by non-clinical managers.[4] Therefore, the literature supports the hypothesis that physician executive leaders can produce better outcomes for the facility and for patients themselves.

While Dr. Adams is but one of many physician executive leaders, his distinct skillset as an anesthesiologist and public health leader have distinguished him as a unique leader in the field. Armed with a background in team management, anesthesiology clinicians are well-poised to follow his example and begin the ascent to leadership — at the local, hospital-wide, and even national level.

[1] https://www.asahq.org/about-asa/newsroom/news-releases/2017/08/jerome-adams-confirmation

[2] https://www.uschamberfoundation.org/bio/jerome-adams

[3] https://hbr.org/2010/04/turning-doctors-into-leaders

[4][4] https://www.ncbi.nlm.nih.gov/pubmed/21802184