The implementation of new debt-free scholarship programs in four top-tier medical schools could have a tremendous impact on the future of the physician workforce. Often a huge disincentive to attending medical school, the grave cost of a medical education can place an insurmountable barrier for students with great financial need. However, large donations by various foundations and university alumni are aiding universities in making medical school a tuition-free endeavor.

Schools implementing this initiative are attempting to address the high debt and loan dependence of affording a medical education. To this end, schools like Columbia University, New York University, Cornell University, and the Kaiser Permanente School of Medicine, are implementing new financial aid programs that replace student loans with scholarships. In addition, some of these scholarships are not only covering tuition, but also books, food, and other related expenses. The funding for these initiatives is supported by multiple funding sources including an endowment fund, and donations from various foundations, organizations, and alumni. Moreover, this tuition-free initiative does not ignore dual-degree students who pursue M.D.-Ph.D. degrees. Students seeking a dual-degree will be provided full tuition and living expenses stipends from different funding sources including the National Institutes of Health.

The scholarship program comes as a result of high medical school tuition costs. Currently, the median cost of tuition and fees of attending a private medical school averages at almost $83,000 per year. Medical students who take out loans to afford these costs graduate with a median debt of $200,000. Universities hope that these scholarships can remove the financial burden of taking out such loans.

Notably, these tuition scholarship programs are expected to also encourage more students from all backgrounds to apply and ultimately attend medical school. A surge in applications to NYU School of Medicine serves as a testament to the increasing numbers of students applying from underrepresented backgrounds. In fact, NYU School of Medicine experienced an increase of almost 3,000 applications with applications from underrepresented minorities up more than 100 percent.

However, donors and university leaders hope that students will be encouraged to seek a diversity of medical paths without regard for debt. Indeed, past studies show that debt can have an impact on the practice that students choose to pursue. A survey fielded by the Association of American Medical Colleges’ Medical School Graduation found that about twenty percent of medical students consider their student debt to be either a strong or moderate influence on the specialty they choose to follow. In addition, a 2014 Medical Education Online study of 3,032 medical students, found that higher-debt students were less likely to have plans to practice in underserved areas. By removing students’ sizable loans, donors hope students can diverge from lucrative career paths to pursue careers in research-oriented specialties, family practice or pediatrics.

Perhaps most importantly, these scholarships have implications for the future workforce of primary care physicians. A 2014 study, examining the relationship between educational debt and primary care specialty choice suggests that limiting high levels of debt, particularly for students with need-based loans, could promote a larger workforce of primary care and family medicine physicians. Through a retrospective multivariate analysis of data on more than 130,000 physicians who graduated in the years 1988-2000, researchers found that students were more likely to practice in primary care or family medicine, when their debt was low (debt levels of $50,000-100,000). The conclusions of this study hold deep implications for lower-income students and suggest that if scholarship funds are targeted effectively it could grow the primary care physician workforce.

Peripheral nerve injury (PNI) after peripheral nerve block (PNB) is usually temporary, lasting a few days to weeks.1 According to Barrington et al, short-term nerve damage (lasting longer than 48 hours) occurs in less than 1 in 10 cases, with 92-97% of patients recovering within six weeks and 99% of patients recovering within a year.2 However, permanent nerve damage occasionally occurs. Retrospective studies report an incidence of 0.5-1.0%, while a prospective study reports an incidence of 10-15% for permanent nerve damage.3 Patients with PNI may report mild changes in sensation such as numbness; or in more severe cases, muscle weakness, severe pain, and permanent paralysis in the affected area.5

The prognosis for PNI depends on the severity of the injury and the residual integrity of the nerve. The most commonly used classification for PNI severity is the three-tiered Seddon system, which includes neuropraxia, axonotmesis, and neurotmesis. In neuropraxic injuries, the myelin sheath is damaged due to stretching or compression, but the axon and supporting tissues (i.e. endoneurium, perineurium, and epineurium) remain intact.5 The prognosis for neuropraxia is quite favorable, with complete recovery occurring within weeks to months.5 Axonotmesis refers to injury of the axon, endoneurium, and perineurium due to fascicular impalement, nerve crush, or toxicity.5 The prognosis for axonotmesis is fair and depends on the extent of disruption to the perineurium and the distance to the corresponding muscles.5 Neurotmesis refers to complete transection of the nerve (including the axons, endoneurium, perineurium, and epineurium) and requires surgical intervention.5 The prognosis for neurotmesis is often poor.

The mechanisms of PNI fall into three categories: mechanical, vascular, and chemical. Mechanical mechanisms include compression, stretch, laceration, and injection injuries. Compression of the nerve produces a conduction block, which may lead to demyelination of axons and PNI if prolonged.5 Needle-related trauma may result from needle-nerve contact or injection into the nerve itself.5 In the event of intraneural injection, nerve ischemia and PNI may result if the intraneural pressure exceeds the capillary occlusion pressure.5 To reduce the risk of block-related PNI, the New York School of Regional Anesthesia recommends avoiding intrafascicular needle placement and injection.

Vascular injuries involve damage to the nerve vasculature (due to direct vascular injury, acute occlusion of the arteries, or hemorrhage within a nerve sheath), resulting in local or diffuse ischemia.5 As an early response to ischemia, neurons depolarize and generate spontaneous activity, symptomatically perceived as paresthesias (i.e. pins and needles).6 As the neurons fire and calcium accumulates intracellularly, there is a blockade of slow-conducting myelinated fibers and eventually all neurons.6 If ischemic times are less than 2 hours, nerve function returns within 6 hours. However, with 3 or more hours of reperfusion, edema and fiber degeneration develop (lasting 1-2 weeks), followed by a phase of regeneration (lasting 6 weeks).6-7

Chemical injuries occur due to toxicity of injected solutions or their additives. In cell cultures, local anesthetics produce a variety of cytotoxic effects, including inhibition of cell growth, motility, and survival.6 The extent of these cytotoxic effects depends on concentration and length of exposure. In the clinical setting, however, the site of injection is most critical to determining the pathogenic potential of local anesthetics.8 If injected intrafascicularly, most chemical substances lead to severe fascicular damage. In a recent rodent model, for example, Whitlock showed that intrafascicular injection of 0.75% ropivacaine resulted in severe demyelination and axonal degeneration.9 Notably, even intrafascicular injection of saline results in intermediate nerve damage.5 If injected intraneurally (but not interfascicularly), most chemical substances cause little or no detectable injury at all.5 Therefore, the location of the needle tip during injection of local anesthetics is a key determinant of the likelihood and severity of chemical injuries.

In summary, PNB-associated neurological complications result from mechanical fascicular trauma or intrafascicular injection of local anesthetics, causing demyelination and axonal degeneration. The primary mechanisms of nerve injury include mechanical injury, ischemia, and toxicity. Avoidance of intraneural injection is a key safety measure that limits the incidence of PNI. With the increased use of ultrasound-guided needle placement, anesthesiologists will improve their ability to detect needle-nerve contact, avoid intraneural injection, and minimize cases of PNI.5

References

1) Fischer B. “Complications of Regional Anaesthesia.” Anaesth Intens Care Med. 2004; 4: 125–128.

2) Barrington M et al. “Preliminary Results of the Australasian Regional Anaesthesia Collaboration. A Prospective Audit of More Than 7000 Peripheral Nerve and Plexus Blocks for Neurologic and Other Complications.” Reg Anesth Pain Med. 2009; 34: 534–541.

3) Liguori GA. “Complications of regional anesthesia: nerve injury and peripheral neural blockade.” J Neurosurg Anesthesiol. 2004; 6: 84-86.

4) Hopper R and Turner J. “Nerve damage associated with peripheral nerve block.” Royal College of Anaesthetists. 2016.

5) Barrington M, Brull R, Reina M, and Hadzic A. “Complications and Prevention of Neurologic Injury with Peripheral Nerve Blocks.” New York School of Regional Anesthesia. 2019.

6) Borgeat A, Blumenthal S, and Hadžic A. “Mechanisms of Neurologic Complications with Peripheral Nerve Blocks.” Complications of Regional Anesthesia. 2007.

7) Selander D and Sjostrand J. “Longitudinal spread of intraneurally injected local anesthetics. An experimental study of the initial neural distribution following intraneural injections.” Acta Anaesthesiol Scand. 1978; 22: 622–634.

8) Selander D. “Neurotoxicity of local anesthetics: animal data.” Reg Anesth. 1993; 18: 461–468.

9) Whitlock EL, Brenner MJ, Fox IK, et al. “Ropivacaine-induced peripheral nerve injection injury in the rodent model.” Anesth Analg. 2010; 11: 214-220.

Local anesthetics are frequently used in the practice of anesthesia and many other areas of medicine as a method to achieve localized pain control and to reduce the use of opiates and other intravenous and oral pain medications. When using local anesthetics, it is imperative to understand and be prepared to treat local anesthetic systemic toxicity (LAST), a life-threatening reaction to local anesthetics that, though rare (due to increased awareness), is extremely dangerous and can possibly result in cardiac arrest. Local anesthetics are quite safe when used in correct dosages and infiltrated in local tissues, however when large dosages are injected and make their way into the bloodstream, systemic toxicity can ensue.

Local anesthetics (most commonly used examples are lidocaine, ropivacaine, bupivacaine, and mepivacaine) work via sodium channel blockade, halting the influx of sodium into cell membranes, thereby stopping the action potential and nerve conduction of nociceptive nerve fibers. Local anesthetic toxicity arises when local anesthetics are used either in excess of their maximum dose, or injected unknowingly into a vascular bed, which results in systemic effects rather than the desired halting of painful nerve conduction locally. The signs and symptoms of LAST vary depending on severity, which is often a correlate of serum concentration. More minor, early signs of LAST include numbness of the tongue, visual and auditory disturbances, and lightheadedness. Patients may also experience tinnitus, paresthesias, and muscle twitches. As serum concentration of the local anesthetic rises, symptoms become more serious and life threatening, including seizures, respiratory depression, and cardiac arrest. Additional cardiac signs of LAST include profound hypotension via vasodilation, AV block, and ventricular dysrhythmias. In addition, there are some differences in toxicity presentation depending on the specific local anesthetic used. Lidocaine, for example usually has preceding neurologic signs prior to cardiac, whereas LAST secondary to bupivacaine will often first manifest with cardiac disturbances.

The most effective treatment for LAST is prevention. Each local anesthetic has a maximum recommended dosage based on the drug used and patient’s weight. This dose should not be exceeded and should be based on patient’s ideal (not total) body weight. Many overdoses occur when a patient requires multiple nerve blocks in multiple locations, making it easier mistakenly give too much medication overall. In addition, extremes of age, hyperdynamic circulation (pregnancy, uremia), and end organ dysfunction all increase an individual patient’s risk of LAST. Practitioners must especially be aware of patients with very low weights (and therefore low maximum doses), as when giving lidocaine to a neonate for a circumcision. Finally, when injecting local anesthetic into tissue, one should always aspirate prior to injection to assure the needle is not intravascular.

In the event of LAST, or suspected LAST (which includes any physiological disturbance after local anesthetics are given), one should stop the offending agent immediately. If the patient does not already have monitors, they should be placed quickly including pulse oximeter, blood pressure monitor, and continuous EKG monitoring. One hundred percent oxygen should be started to prepare for respiratory compromise or collapse and to avoid hypoxia (which worsens LAST). If cardiovascular collapse occurs, ACLS and CPR should be initiated and all cardiopulmonary life-saving measures should be considered. Patients should be hyperventilated to treat hypercapnia and if seizing, patient should be treated with benzodiazepines – propofol should be avoided due to cardiac depressant and vasodilatory effects. Finally, the mainstay of treatment of LAST is intralipid emulsion therapy (20% intralipid), which should be available whenever local anesthetics are used. Intralipid should be given as an initial bolus of 1.5 ml/kg and then followed with an infusion 0.25ml/kg/min until the patient has stabilized.

References:

Heavner JE. Local anesthetics. Curr Opin Anaesthesiol 2007; 20:336.

Scholz A. Mechanisms of (local) anaesthetics on voltage-gated sodium and other ion channels. Br J Anaesth 2002; 89:52.

Wolfe JW, Butterworth JF. Local anesthetic systemic toxicity: update on mechanisms and treatment. Curr Opin Anaesthesiol 2011; 24:561.

Di Gregorio G, Neal JM, Rosenquist RW, Weinberg GL. Clinical presentation of local anesthetic systemic toxicity: a review of published cases, 1979 to 2009. Reg Anesth Pain Med 2010; 35:181.

Gitman M, Barrington MJ. Local Anesthetic Systemic Toxicity: A Review of Recent Case Reports and Registries. Reg Anesth Pain Med 2018; 43:124.

Thomson PD, Melmon KL, Richardson JA, et al. Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans. Ann Intern Med 1973; 78:499.

Anesthetic complications in plastic surgery are generally rare, but potentially catastrophic. Thus, maintaining patient safety in the operating room is a major concern of anesthesiologists, surgeons, hospitals, and surgical facilities. Circumventing preventable complications is essential and pressure to avoid these complications in plastic surgery is increasing (1). Although all surgeries carry risk, there are often additional factors pertaining to plastic surgeries that may aggravate existing comorbid conditions. Patients undergoing plastic surgeries often present complex and difficult scenarios that anesthesiologists must take into account. These case scenarios can be classified as 1) those inherent to the age of the patients in which these conditions appear, 2) those with medical comorbidities involved, and 3) conditions that pose difficulties in airway management (1).

Pediatric patients often have congenital defects, such as cleft lip and palate, that present difficulties for anesthesiologists. These include issues with ventilation and intubation, for example. In a review of perioperative airway complications following pharyngeal flap palatoplasty, Peña et al. reported a ten percent incidence of airway complications in the 88 patients studied (2). For these patients, intravenous access may need to be established before the induction of anesthesia. Using straight laryngoscope blades, external laryngeal manipulation and a piece of rolled gauze packed in the cleft palate defect may help. Fiber-optic bronchoscopes, Bullard laryngoscopes and laryngeal masks are also other alternatives for securing the airway. Elderly patients are also at greater risk for perioperative complications. This is due to the combined effects of reduced organ function and the prevalence of age related concomitant diseases. The risks associated with plastic surgery and anesthesia in this age group can be minimized by understanding the physiological changes associated with aging (1). Elderly patients are more prone to heat loss and shivering, for example, due to a reduced basal metabolic rate and impaired thermoregulation. Drug metabolism is also slower in elderly patients, as they generally have reduced renal and liver function, leading to increased susceptibility to drug-related toxicity. Additionally, the incidence of postoperative delirium in the elderly population is almost 10%. Causes may include patients’ age, baseline low cognitive function, dementia and depression.(3). Delirium is also associated with increased duration of hospital stay and poorer functional recovery.

Case scenarios with medical comorbidities involved, such as surgeries for obese patients, diabetics, and burns patients also add complexity to the role of the anesthesiologist. The most common surgery that obese patients choose to undergo is liposuction, and the complications associated with this procedure can vary from mild to severe, including death (1). Generally, liposuction requires the use of wetting solution (containing epinephrine and lidocaine) to minimize blood loss. Excess wetting solution may lead to lidocaine toxicity. However, if the patient receives general anesthesia, the lidocaine component of the wetting solution can be further reduced or eliminated without an increase in postoperative pain (1). Patients with conditions like diabetes and hypertension often undergo surgeries such as debridement and flap cover. Both of those procedures are associated with significant blood loss, hypothermia, cognitive dysfunction and other complications associated with being in the prone position. The most common complications associated with the prone position are injuries to the central nervous system, injuries to peripheral nerves (ulnar neuropathy), direct pressure injuries (to ears, breasts, genitalia and other dependent areas) and peripheral vessel compression and occlusion. It is advisable to maintain a neutral neck position to minimize the risk of occluding the carotid or vertebral arteries and internal jugular veins (4). As for patients with acute burns, anesthesiologists should be careful to avoid succinylcholine for muscle relaxation in major burns (more than 10% of total body surface area), if more than 24 hours old. Succinylcholine can cause hyperkalemia and possibly cardiac arrest. Non-depolarizing muscle relaxants (e.g., pancuronium, vecuronium, etc.) may be used, although higher doses may be required (1).

Last but not least, conditions that pose difficulty in airway management can also add complications to anesthesia delivery. One of the most common conditions where difficulty in airway management can be expected is maxillofacial trauma (1). The difficulties associated with this condition can be avoided by carefully timing the surgery, so that tissue edema subsides but malunion of the facial bones does not occur. Maxillofacial reconstruction is often required to correct the effects of trauma (e.g., Le Fort fractures) and developmental malformations. Preoperative airway evaluation must be detailed and thorough, as the presence of active hemorrhaging, for example, may pose difficulty in fiberoptic laryngoscopy. If there are any anticipated signs of problems with mask ventilation or tracheal intubation, the airway should be secured prior to induction. This may involve fiberoptic nasal intubation, fiberoptic oral intubation or tracheostomy (1).

References

1. Nath, S. S., Roy, D., Ansari, F., & Pawar, S. T. (2013). Anaesthetic complications in plastic surgery. Indian Journal of Plastic Surgery: Official Publication of the Association of Plastic Surgeons of India, 46(2), 445–452. doi:10.4103/0970-0358.118626
2. Peña, M., Boyajian, M., Choi, S., & Zalzal, G. (2000). Perioperative Airway Complications following Pharyngeal Flap Palatoplasty. Annals of Otology, Rhinology & Laryngology, 109(9), 808–811. https://doi.org/10.1177/000348940010900904
3. Dasgupta, M. and Dumbrell, A. C. (2006). Preoperative Risk Assessment for Delirium After Noncardiac Surgery: A Systematic Review. Journal of the American Geriatrics Society, 54: 1578-1589. doi:10.1111/j.1532-5415.2006.00893
4. Edgcombe, H., Carter, K., Yarrow, S. (2008). Anaesthesia in the prone position. British Journal of Anaesthesia, 102(2), 165-183. doi: 10.1093/bja/aem380

Studies on the mechanism of peripheral nerve block focus on the interaction of local anesthetics with voltage-gated sodium channels.¹ Part of a superfamily of tetrameric transmembrane glycoproteins, sodium channels initiate and propagate action potentials in axons, dendrites, and muscle tissue.^2-3 Sodium channels exist in three conformations: open, inactivated, and resting. During a neural impulse, the membrane potential becomes less negative as Na⁺ conductivity increases. At threshold, sodium channels “open” and the membrane potential shoots up.³ After a few milliseconds, sodium channels “inactivate” and the membrane potential returns to baseline.³ Once the membrane repolarizes, sodium channels return to their “resting” conformation.¹ As is soon described, sodium channel conformation plays a key role in the functioning of local anesthetics.

As early as 1959, Taylor confirmed that local anesthetics selectively bind and inhibit sodium channels in nerves.⁴ Subsequent research localized the drug-binding site to the inner pore of the sodium channel, where local anesthetics primarily interact with a phenylalanine in domain IV S6.⁵ According to Fozzard et al, the affinity of local anesthetics for the binding site depends upon the conformation of the sodium channel. When the sodium channel is in its closed state, the binding affinity is low and Na⁺ current is only blocked at high concentrations (mM range).⁵ In contrast, the binding affinity is much higher in the open and open-inactivated states, during which the voltage sensors are deployed outward.⁵

Strichartz was first to observe the frequency-dependence of local anesthetics.⁶ According to the model, local anesthetic inhibition of Na⁺ current increases with repetitive depolarizations.¹ Statistically, the percentage of sodium channels in the open and open-inactivated states at any given moment increases as the frequency of action potentials inceases.¹ Since the binding affinity is higher for the open state relative to the resting state, a lower concentration of anesthetics is therefore needed at higher frequencies.¹

Although the biochemistry at the binding site is well understood, it is not fully understood how local anesthetics block Na⁺ current at the biophysical level. One possible mechanism is that local anesthetics obstruct the inner pore of sodium channels. Molecular modeling from Hanck et al is consistent with the idea that local anesthetics bind horizontally across the pore.⁷ According to Sunami et al, the high-affinity binding site is about 10 Å below the selectivity filter, where charged ligands block the channel by occupying sites NaIII or NaIV for permeant ions.^2,7 Even if the channel is not completely obstructed, the positive charge placed at the innate sites creates an electrostatic barrier that blocks Na⁺ influx by Coulombic repulsion.² Therefore, local anesthetics block Na⁺ current by a combination of physical and electrostatic obstruction.

An alternative explanation is that local anesthetics interfere with gating. In this model, local anesthetics reduce the movement of charged residues in the voltage sensor, or gating current.⁵ More specifically, Fozzard et al found that the binding of local anesthetics to phenylalanine locks domain III S4 in its outward position. This prevents the voltage sensor from resetting during repolarization, thereby disrupting the gating mechanism of sodium channels and blocking Na⁺ current.⁵

In summary, local anesthetics bind to a phenylalanine in domain IV S6 of sodium channels. The affinity of local anesthetics for this binding site is highest when the sodium channel is in the open state. Once at the binding site, local anesthetics create a physical and electrostatic barrier that blocks Na⁺ current. In addition, local anesthetics may also interfere with the gating mechanism of sodium channels. Further research is still needed to clarify the biophysical mechanisms by which local anesthetics block Na⁺ current.

References:

1) Becker, Daniel, and Reed, Kenneth. “Local anesthetics: review of pharmacological considerations.” Anesthesia progress vol. 59, 2 (2012): 90-101.

2) “Clinical Pharmacology of Local Anesthetics.” New York School of Regional Anesthesia. 2019.

3) Vadhanan, Prasanna et al. “Physiological and pharmacologic aspects of peripheral nerve blocks.” Journal of anaesthesiology, clinical pharmacology vol. 31, 3 (2015): 384-93.

4) Taylor, RE. “Effect of procaine on electrical properties of squid axon membrane.” Am J Physiol vol. 196 (1959): 1070–1078.

5) Fozzard, Harry et al. “The sodium channel as a target for local anesthetic drugs.” Frontiers in pharmacology vol. 2, 68. 1 Nov. 2011.

6) Strichartz, GR. Local Anesthetics: Handbook of Experimental Pharmacology. Springer-Verlag, 1987.

7) Sunami, A, Dudley, SC, and Fozzard, HA (1997). “Sodium channel selectivity filter regulates antiarrhythmic drug binding.” Proc. Natl. Acad. Sci. U.S.A.