Anesthesia: looking back at the last century and forward to the next.

Unlike many other subspecialties, most anesthesiologists can tell you when our specialty began: October 16, 1846, when the first ether anesthetic was delivered by Dr. William Morton in what is now affectionately called the "Ether Dome" of the Massachusetts General Hospital. From that day and certainly over the past 100 years, the field of anesthesia has continued to grow and florish. The growth has been both scientific and philosophical, the latter being exemplified by the change in name from Departments of Anesthesiology to Departments of Anesthesiology & Perioperative Medicine in many academic institutions. Perioperative medicine has been viewed as involving the preoperative preparation of patients, intraoperative care, and postoperative management in the areas of ICU care and pain management. The interest and involvement of anesthesiologists outside of the operating room has led many departments to play a significant role in critical care and pain management. The scientific development of anesthesia over the past century has involved pharmacology, technology, and the science of our specialty with in-depth investigations into the mechanisms of action of anesthetic agents, quality improvement, and patient outcomes. The latter areas have provided us with valuable information as to how better to care for our patients and limit perioperative morbidity and mortality.

Perhaps the greatest advancements in anesthesia have come in the arena of pharmacology. These advancements have provided the anesthesia caregiver with improvements in the potent inhaled anesthetic agents, IV induction agents, neuromuscular blocking agents, and analgesics including opioids and nonsteroidal anti-inflammatory agents (NSAID) to name just a few. After the first ether anesthetic, there was a recognition that improvements were necessary to improve patient safety and achieve better outcomes. Ether, cyclopropane, and methoxyflurane were abandoned in favor of halothane and isoflurane. These developments improved the safety not only for our patients, but also for those in the operating room, as flammable and explosive agents such as cyclopropane were no longer required. Halothane, although effective for inhalation induction, was the leading cause of death due to perioperative cardiac arrest in infants and children related to its potent negative inotropic and chronotropic effects. In most centers, halothane has been replaced by sevoflurane, a substituted methyl-isopropyl ether that like halothane is nonpungent and nonirritating to the airways thereby making it a suitable agent for inhalation induction in patients of all ages. Chemical modification has also made sevoflurane less soluble in blood than halothane, thereby allowing for a more rapid rise in its alveolar concentration and a more rapid induction of anesthesia. When compared with halothane, sevoflurane lacks the potent negative inotropic and chronotropic effects, thereby making the inhalation induction of anesthesia safer. The newest member of the inhalational anesthetic class, desflurane, has found a role in outpatient anesthesia and beyond, given its rapid elimination, thereby providing a rapid recovery. This effect has encouraged its use in outpatient or fast-track anesthesia where the goal is to bypass stage 1 recovery, thus saving money and time.

The goal of rapid recovery and discharge has led to the development of new IV anesthetic agents with short plasma half-lives such as propofol. Propofol, used either as an induction agent followed by maintenance with an inhalational agent or a continuous infusion (also known as TIVA, or total IV anesthesia), provides another option for rapid room turnovers and patient discharge. When compared with the time-honored IV induction agent, the barbiturates, propofol allows for a more rapid return of consciousness, a smooth recovery, limited hangover effect, and decreased postoperative nausea and vomiting. The addition of generic forms of this agent to the market has dramatically lowered the cost. Although suitable and effective in the operating room, propofol reminds us of the potential for unseen dangers with new medications. When propofol was taken out of the operating room and used for prolonged sedation in the Pediatric ICU, there were isolated deaths related to what has now come to be known as the propofol infusion syndrome. Further work has suggested that in specific yet undefined patients, propofol may inhibit oxidative phosphorylation in the mitochondria resulting in fatal myocardial failure. Similar issues of the potential dangers of the prolonged use of medications were seen in the 1980s when etomidate was used for ICU sedation. Repeated doses or the continuous infusion of etomidate inhibits the adrenal production of corticosteroids and resulted in an increased mortality in the adult ICU population. These issues serve as important reminders that although these agents are valuable additions to the anesthesiologist's pharmacologic armamentarium, there may be potentially hidden dangers with new medications.

The expansion of anesthetic pharmacology has provided us with several new neuromuscular blocking agents (NMBAs) which far exceed the efficacy and utility of the original compound, curare. We have shorter-acting agents as well as agents which are not dependent on hepatic or renal function for elimination. Despite extensive research, we have also learned that newer is not always better. When faced with the need to rapidly secure the airway, there is still nothing that can replace succinylcholine. However, over the years we have also learned the real dangers with depolarizing NMBAs like succinylcholine, especially in the pediatric population, which has better defined when its use is appropriate. The NMBAs have also shown us that there may be potentially unrecognized dangers with new medications which are not fully appreciated until these agents are released for clinical use. Rapacuronium was supposed to rival succinylcholine with regards to onset and offset, yet was removed from the market shortly after its release related to reports of bronchospasm and even death in some patients.

The technology of anesthesiology also continues to increase exponentially. Within the last 20 years, we have seen the widespread use of end-tidal [CO.sub.2] monitoring and pulse oximetry in the operating room. Technology strives to provide us with the means to monitor our patient's physiologic functions such as cardiac output without invasive procedures such as placement of a pulmonary artery (PA) catheter. To date, the perfect noninvasive monitor of cardiac output remains to be developed, but the expansion of transesophageal echocardiography may give us the same information as PA catheters and then some. Recent concerns and reports of awareness during anesthesia have resulted in the suggestion from the American Society of Anesthesiologists that some form of consciousness monitoring should be considered during the provision of general anesthesia. These monitors provide our patients with peace of mind in addition to decreasing the incidence of awareness and potentially providing a more rapid recovery and decreased use of anesthetic agents. Near infrared spectroscopy may provide us with a means of non-invasively monitoring cerebral oxygenation; preliminary data suggest that monitoring cerebral oxygenation and maintaining it may decrease postoperative neurocognitive dysfunction in the elderly. Technology has also spilled over into the area of pain management with the development and widespread use of patient-controlled analgesia, peripheral nerve blockade, and even disposable, single-use devices that allow the continuous infusion of local anesthetic agents for outpatients.

The significant increase in the various aspects of anesthesiology has necessitated the expansion of the training curriculum from 3 to 4 years. There is also discussion of the need to revise the current 4-year curriculum into a true 4-year program and not an internship plus 3 years of clinical anesthesiology. The latter would allow the incorporation of more critical care and specific anesthesia-related training during the first year. Increased recognition of the need for subspecialty training has led to the development and now credentialing of fellowships in several areas of anesthesiology and the institution of board certification in critical care and pain management.

The future will likely bring us better noninvasive monitoring and more pharmacology. The current move is toward the development of isolated enantiomeres of many of our medications rather than the use of racemic mixtures. It is hoped that these enantiomeres will posses the beneficial qualities of the parent compound while limiting the side effect profile. Such work has resulted in the introduction of levobupivcaine, ropivacaine, and S(+) ketamine into clinical practice. It is likely that the greatest impact of the future will be a better understanding of the genetics of critical care and anesthesiology. We have only scratched the surface, but now realize that our genome may control how we respond to anesthetic agents as well as our potential for having specific postoperative morbidity following major surgical procedures including cardiopulmonary bypass. It may be feasible to map our genome and develop a tailored-made anesthetic and perioperative regimen which facilitates our postoperative recovery and limits morbidity and mortality.

Additional Selected Readings

1. Morray JP, Geiduschek JM, Ramamoorthy C, et al. Anesthesia-related cardiac arrest inchildren: initial findings of the Pediatric Perioperative Cardiac Arrest (POCA) Registry. Anesthesiology 2000;93:6-14.

2. Wagner RL, White PF, Kan PB, et al. Rosenthal MH. Inhibition of adrenal steroidogenesis by the anesthetic etomidate. New Engl J Med 1984;310:1415-1421.

3. Bray RJ. Propofol infusion syndrome in children. Paediatr Anaes 1998; 8:491-499.

4. Schenkman KA, Yan S. Propofol impairment of mitochondrial respiration in isolated perfused guinea pig hearts determined by reflectance spectroscopy. Crit Care Med 2000;28:172-177.

5. Jooste E, Zhang Y, Emala CW. Rapacuronium preferentially antagonizes the function of M2 versus M3 muscarinic receptors in guinea pig airway smooth muscle. Anesthesiology 2005;102:117-124.

6. Rajchert DM, Pasquariello CA, et al. Rapacuronium and the risk of bronchospasm in pediatric patients. Anesth Analg 2002;94:488-493.

7. Tobias JD, Johnson JO, Sprague K, et al. Effects of rapacuronium on respiratory function during general anesthesia: a comparison with cisatracurium. Anesthesiology 2001;95:908-912.

8. Larach MG, Rosenberg H, Gronert GA, et al. Hyperkalemic cardiac arrest during anesthesia in infants and children with occult myopathies. Clin Pediatr 1997;36:9-16.

9. Yao FSF, Tseng CCA, Ho CYA, et al. Cerebral oxygen desaturation is associated with early postoperative neuropsychological dysfunction in patients undergoing cardiac surgery. J Cardiothor Vasc Anesth 2004;18:552-558.

10. Casati A, Fanelli G, Pietropaoli P, et al. Continuous monitoring of cerebral oxygen saturation in elderly patients undergoing major abdominal surgery minimizes brain exposure to potential hypoxia. Anesth Analg 2005;101:740-747.

11. Ekman A, Lindholm ML, Lennmarken C, et al. Reduction in the incidence of awareness using BIS monitoring. Acta Anaesthesiol Scand 2004;48:20-26.

12. Sandin RH, Enlund G, Samuelsson P, et al. Awareness during anaesthesia: a prospective case study. Lancet 2000;355:707-711.</p> <pre> Knowing is not understanding. There is a great difference between knowing and understanding: you can know a lot about something and not really understand it. --Charles Kettering </pre> <p>Joseph D. Tobias, MD

From the Departments of Anesthesiology and Pediatrics, University of Missouri, Columbia, MO.

Reprint requests to: Joseph D. Tobias, MD, Vice-Chairman, Department of Anesthesiology, Chief, Division of Pediatric Anesthesiology, Russell and Mary Shelden Chair in Pediatric Intensive Care Medicine, Professor of Anesthesiology and Child Health, University of Missouri, Department of Anesthesiology, 3W40H, One Hospital Drive, Columbia, MO 65212. Email: [e-mail]

Accepted January 12, 2006.