Forthcoming Issues in Clinical Anesthesia

From the 62nd Postgraduate Assembly in Anesthesiology, sponsored by the New York State Society of Anesthesiologists, New York , NY

Educational Objectives

The goal of this program is to improve judicious use of anesthesia by reviewing the evidence about neurotoxicity and predictions of future trends in anesthesia care. After hearing and assimilating this program, the clinician will be better able to:

1.   Describe current theories on how anesthesia affects the developing brain.

2.   Discuss the studies in children that show subtle but inconclusive changes in intellectual cognitive function after anesthesia.

3.   Explain why the polymerization of neuronal proteins induced by certain volatile anesthetics concerns clini­cians who treat the elderly.

4.   Identify population and workforce trends that will necessitate increased productivity from anesthesia provid­ers.

5.   List examples of industrial principles that can be adapted to anesthesia practice to increase quality of care and productivity.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any per­sonal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the faculty and the planning committee reported nothing to disclose. In his lecture, Dr. Abenstein discussed the off-label or investiga­tional use of a therapy, product, or device.

Acknowledgements

Drs. Drummond and Abenstein were recorded at the 62nd Postgraduate Assembly in Anesthesiology, held December 12-16, 2008, in New York, NY, and sponsored by the New York State Society of Anesthesiologists. The Audio-Digest Foundation thanks the speakers and the New York State Society of Anesthesiologists for their cooperation in the pro­duction of this program.  

Anesthetics in the Coming Years

John C. Drummond, MD, Professor of Anesthesiology, University of California, San Francisco, School of Med­icine

Lasting neurotoxicity of anesthetic agents: probably influenced in part by genetics; extensive animal research sug­gests anesthetics currently in use have enduring neurotoxicity, especially in very young and very old individuals

Pediatric evidence: studies of nematode Caenorhabditis elegans show organism born with 1019 neurons and loses »130 of those neurons due to apoptosis during maturation; suggests disposal of unnecessary neurons may be in part genetically programmed; in 1999, Olney and colleagues demonstrated neuronal apoptosis in neonatal rats given N-methyl-D-aspartate (NMDA) glutamate receptor antagonist (NMDA glutamate receptors [excitatory receptors] used widely by brain); in 2003, Jevtovic-Todorovic showed administration to rat pups of commonly used pediatric anesthetics associated with neuronal apoptosis and reduced learning capacity in adulthood; Olney et al previously demonstrated that all volatile anesthetics inhibit NMDA receptors; proposed mechanism  —  in utero and during early postnatal period, developing neurons send out axons to make appropriate connections with dendrites of other neurons; if connection made properly, stable synapse results; requires complicated exchange of neurotransmitters and growth factors across synapse; if connection not established, apoptosis of involved neuron ensues; volatile an­esthetics block NMDA glutamate receptors and cause “abnormal” inhibition (human brain has no endogenous NMDA glutamate antagonists; magnitude of inhibition produced by anesthetics also abnormal); in developing brain, anesthetics may prevent establishment of developing synapses or shut down established synapses; body may interpret inhibition as permanent synaptic loss, with subsequent apoptosis and elimination of “unnecessary” neu­rons; period of brain vulnerability to anesthetic-induced apoptotic loss corresponds to period of most active synap­tic development (from birth to first 20-30 days of life in rodents; from birth through age 4 yr in humans); leads to question of whether administration of anesthetic to human children produces demonstrable impairment of intellec­tual ability; Soriano and colleagues demonstrated no significant differences in intellect between children given an­esthesia for cardiac surgery and control group (very subtle differences seen); later studies by different investigators suggest pediatric anesthesia associated with slightly lower cognitive or intellectual function, but conclusive evi­dence still lacking

Geriatric evidence: critical synapses occur at dendritic spines; preliminary evidence suggests volatile anesthetics cause rapid regression of spines (normal function restored through redevelopment of spines and re-establishment of synapses); elderly thought to be at greatest risk for anesthesia-induced dendrite loss (animal studies demonstrate loss of dendritic spines in middle age and beyond); in studies by Culley and colleagues, administration of isoflu­rane-nitrous oxide anesthetic to elderly rats associated with memory impairment; mechanism unknown (in vitro studies by same investigators show isoflurane causes apoptotic neuronal loss); no evidence of similar effect in hu­mans (studies by Rasmussen and colleagues show no cognitive impairment among elderly patients 3 mo after sur­gery; Carnini and colleagues showed volatile anesthetics have potential to cause polymerization of neuronal proteins that normally exist as monomers; some polymers produced are proteins associated with Parkinson  or Al­zheimer disease (eg, b amyloids); other investigators found no evidence of cognitive dysfunction 6 yr after coro­nary interventions; some observers fear procedures may induce slight but undetectable change that hastens future cognitive decline; current tests of cognitive function may not be subtle enough to detect changes induced by anes­thetics; no data to justify changing current practice

Conclusion: anesthesia providers may eventually decide to limit use of neurotoxic agents; may refrain from using higher concentrations of NMDA antagonists (ketamine, volatile anesthetics, and nitrous oxide) to avoid risk for un­necessary neuronal apoptosis; may turn, instead, to agonists for endogenous receptors (opioids, enkephalins, and gamma amino butyric acid)

How Might Anesthesia be Delivered?

John P. Abenstein, MD, Associate Professor of Anesthesiology, Mayo Clinic College of Medicine, Rochester, MN

Background: United States population growing and aging rapidly; early years on Medicare coincide with popula­tion’s highest medical demands; growth of nonsurgical therapeutic interventions also rapid; fewer patients now hospitalized; emphasis on outpatient care growing; hospitalized patients older and sicker, and require increas­ingly complex care; most hospital beds now becoming intensive-care beds; return on investment decreasing (eg, cost of left ventricular assist devices approaches $1 million per life-year saved for 100 additional days of life); United States currently spends 16% of gross domestic product on health care (expected to double by 2015); health insurance premiums increased 73% between 2000 and 2005, compared to cumulative inflation and wage growth of 14% during same period; health care costs in other industrialized countries rising at same rate as in United States; costs have increased 251% since 1985; however, college costs have increased >400%

Reimbursement: government programs pay <50% of cost of care; “private medical insurance is at the limit of how much cost-shifting they can afford”

Workforce trends: number of medical school graduates flat for last 30 yr; fewer available clinical full-time equiva­lents (FTEs), due to increasing number of women entering medicine (>50% of medical students now female) and changing attitudes toward work-life balance; work-hour restrictions limit residents’ hours to 80 per wk (may change to 57 hr per wk in 2009); government may require similar limitation in attending physicians’ hours; result will be fewer available clinical FTEs; meanwhile, demand for health care outstripping supply

Impact on medicine: most likely to be “steady but relentless technology-based advances”; example  —computed to­mography and magnetic resonance imaging have eliminated need for most exploratory surgery

Impact on anesthesiologists: anesthesia today easier to administer than 30 yr ago, but patients sicker today, with more comorbidities and physiologic changes; result  —  switch of anesthesiologists’ work effort from adminis­tration of anesthetic to providing medical care; in speaker’s opinion, anesthesiologists should leverage knowl­edge and skills and use technologic advances to increase productivity and improve quality, reliability, and reproducibility of care; will be accomplished through industrial solutions (automated processes overseen re­motely by highly skilled operators, with small number of individuals on floor to troubleshoot)

Examples of industrial technologic advances adapted for medicine: cockpit oversight  —  monitors, anesthesia ma­chines, and infusion pumps interfaced to local area network; information from network sent to cockpit, where individual observes output from monitoring equipment, anesthesia machines, and other devices in operating room; audiovisual hookups permit communication with anesthesia provider in operating room and on floor, so operator can direct them to patients most in need of care; electronic decision support  —  rule-based automated systems that identify clinical syndromes; process and evaluate raw data to detect abnormal physiologic values, including trends and rates of change in patient’s status; abnormalities brought to operator’s attention; perform multimodal analysis (eg, alert clinician to possible hypovolemia, based on detection of associated symptoms of tachycardia and hypotension); systems may also incorporate other information, such as laboratory results and radiology readings; can detect adverse events routinely missed by tired or overly stressed bedside and cockpit clinicians; at Mayo Clinic, pilot studies show electronic “sniffers” can identify transfusion-related lung injury, sepsis, and ventilator-induced lung injury 36 to 48 hr earlier than human clinicians; utility will expand through population-based data analysis of trends and outcomes; other systems monitor hemodynamic data for changes and abnormal readings; systems increase productivity by allowing operator to care for more patients concur­rently; hazardous environment systems  —  devices in hazardous area feed information to control center (eg, cockpit), where operator can adjust processes remotely; newer anesthesia machines fully electronic and allow similar remote adjustment of ventilation, infusion pumps, boluses and fluid administration; almost all anes­thesia management can be done remotely; industrial homeostasis  —  refers to narrow range of temperature and pressure parameters required in chemical and pharmaceutical plants and refineries; computer-based sys­tems use closed-loop control to maintain processes within predefined limits; anesthetic management can be ac­complished through similar closed-loop control that uses physiologic parameters (eg, muscle tone, electroencephalography) as inputs; technology available since 1950

Conclusions: technologic developments should be relatively straightforward; should allow significant increase in pa­tient-physician ratio; anesthesiologists will be able to focus on patients most in need of care; changes in operating room personnel  —  robots and devices that can perform simple procedures (eg, placement of intravenous lines, arte­rial lines, central lines) may eliminate need for skilled personnel at beginning and end of procedure; better monitor­ing systems must be developed; innovations now under development include high-frequency analysis of electrocardiogams; wave-form analysis of plethysmograms and arterial lines; analysis of vital sign variability and rates of change; noninvasive cardiac output, ultrasonography systems, and real-time blood chemistry analysis sys­tems also being developed; determining and monitoring relationship between cardiac and femoral artery blood flow and cardiac output expected further in future; automated ultrasonography and airway sound analysis

Suggested Reading

Abenstein JP: Technology assessment for the anesthesiologist. Anesthesiol Clin 24:677, 2006; Anand KJ, Soriano SG: Anesthetic agents and the immature brain: are these toxic or therapeutic? Anesthesiology 101:527, 2004; Carnini A et al: Interactions of volatile anesthetics with neurodegenerative-disease-associ­ated proteins. Anesthesiol Clin 24:381, 2006; Charabati S et al: Comparison of four different display de­signs of a novel anaesthetic monitoring system, the ‘integrated monitor of anaesthesia’ (IMATM). Br J Anaesth Sept 29, 2009 [Epub ahead of print]; Chung KK et al: Robotic telepresence: past, present, and fu­ture. J Cardiothorac Vasc Anesth 21:593, 2007; Culley DJ et al: General anesthetic-induced neurotoxicity: an emerging problem for the young and old? Curr Opin Anaesthesiol 20:408, 2007; Fields AM et al: Closed-loop systems for drug delivery. Curr Opin Anaesthesiol 21:446, 2008; Ikonomidou C et al: Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 283:70, 1999; Jacques PS et al: Evaluation of a hands-free wireless communication device in the perioperative environment. Telemed J E Health 12:42, 2006; Jevtovic-Todorovic V et al: Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 23:876, 2003; Sapirstein A et al: Tele ICU: paradox or panacea? Best Pract Res Clin Anaesthesiol 23:115, 2009; Steinmetz J et al: Long-term consequences of postoperative cognitive dysfunction. Anesthesiology 110:548, 2009.