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Sympathetic Nervous System Evaluation and Importance for Clinical General Anesthesia Martin Neukirchen, M.D.,* Peter Kienbaum, M.D.†

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Sympathetic Nervous System Evaluation and Importance for Clinical General Anesthesia Martin Neukirchen, M.D.,* Peter Kienbaum, M.D.† Ⅵ REVIEW ARTICLE David S. Warner, M.D., and Mark A. Warner, M.D., Editors Anesthesiology 2008; 109:1113–31 Copyright © 2008, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Sympathetic Nervous System Evaluation and Importance for Clinical General Anesthesia Martin Neukirchen, M.D.,* Peter Kienbaum, M.D.† For more than 100 yr, scientists have studied the sympathetic tem (SNS) to mobilize forces during struggle, whereas nervous system and its cardiovascular control mechanisms. the parasympathetic system regulated hollow organ Muscle sympathetic activity is the most important direct and function and reproduction. In fact, animals from which rapidly responding variable for evaluation of sympathetic neu- ral outflow. Because of its significance in response to environ- the entire sympathetic paravertebral chain was removed mental challenges and its role in cardiovascular control, great survived in a protected environment but could not main- attention has been paid to the sympathetic nervous system in tain normal body temperature, arterial and cerebral per- both health and disease and, more recently, also during general fusion pressures, or constant extracellular fluid volume, anesthesia. In fact, general anesthesia can also be considered as in particular in response to challenges.5 Although these an investigational tool to assess mechanisms of cardiovascular regulation. This review evaluates different methods for deter- observations suggest a uniform reaction of the SNS to mination of sympathetic nervous system activity and describes stress, the autonomic nervous system is nevertheless its role in human neurohumoral circulatory control. Further- highly differentiated, and each organ system seems to be more, the effects of general anesthesia on sympathetic nervous controlled separately.6,7 Accordingly, a general state of system activity and their relevance for clinical anesthesia are increased or decreased sympathetic activity, as often discussed. assumed by clinicians, is unlikely. Rather, one has to consider sympathetic outflow to each individual organ 1 MORE than a century ago, Langley defined the autonomic system separately.8 nervous system as the neural outflow from the central Because of its significance in response to environmen- nervous system to the vasculature and viscera and distin- tal challenges and its role in cardiovascular control, great guished between a sympathetic (thoracolumbar) and a attention has been paid to the SNS in both health and parasympathetic (craniosacral) system. This separation was disease and, more recently, also during general anesthe- based on embryologic development, distribution of inner- sia. In fact, anesthesia can also be considered as an vation to target organs, and opposing effects of electrical investigational tool to assess mechanisms of cardiovas- nerve stimulation or exogenously applied drugs such as cular regulation. This review evaluates the methodology epinephrine, pilocarpine, or atropine. The spinal segments for assessing SNS activity in humans, its role in cardio- of neural outflow to different organs were defined by ex- vascular regulation, and the significance of SNS integrity amining organ function in response to ventral root stimu- during general anesthesia. lation. Furthermore, ganglionic synapses were localized by topical application of nicotine. These studies indicated that organs received both sympathetic and parasympathetic in- nervation and that the stimulatory effects of the systems are Mechanisms and Evaluation of Sympathetic often opposed.1,2 Nervous System Around the same time, Cannon3,4 hypothesized that Methods of Assessment of Sympathetic Activity the autonomic nervous system served the body’s ho- Direct Assessment of Sympathetic Activity by Mi- meostasis. He considered the sympathetic nervous sys- croneurography. Sum action potentials induced by transdermal electrical nerve stimulation can be recorded * Resident in Anesthesiology and Research Fellow, † Staff Anesthesiologist and from human peripheral nerves with surface electrodes. Vice Chairman. In contrast, evaluation of spontaneous nerve traffic re- Received from the Klinik fu¨r Ana¨sthesiologie, Universita¨tsklinikum Du¨sseldorf, quires more sophisticated methods. A technique for re- Du¨sseldorf, Germany. Submitted for publication March 17, 2008. Accepted for publication August 6, 2008. Support was provided solely from institutional cording neural activity via percutaneously inserted in- and/or departmental sources. traneural electrodes was introduced approximately Mark A. Warner, M.D., served as Handling Editor for this article. three decades ago by Hagbarth and Vallbo9 obtaining Address correspondence to Dr. Neukirchen: Klinik fu¨r Anaesthesiologie, Uni- versita¨tsklinikum Du¨sseldorf, Moorenstrasse 5, 40225 Du¨sseldorf, Germany. direct recordings of mechanoreceptive activity from hu- [email protected]. Information on purchasing reprints man peripheral nerves. Concurrently, spontaneous intra- may be found at www.anesthesiology.org or on the masthead page at the neural activity was discovered and recognized as efferent beginning of this issue. ANESTHESIOLOGY’s articles are made freely accessible to all 10 readers, for personal use only, 6 months from the cover date of the issue. sympathetic nerve traffic. Since then, microneurogra- Anesthesiology, V 109, No 6, Dec 2008 1113 1114 M. NEUKIRCHEN AND P. KIENBAUM phy has been increasingly used to investigate human 40%).17 Surprisingly, total-body norepinephrine spill- sympathetic nerve traffic under physiologic and patho- over, as well as renal and cardiac norepinephrine spill- physiologic conditions.11 over, correlates well with MSA despite the proposed Tungsten electrodes (diameter: 200 ␮m) with a tip differential control of sympathetic organ innervation at diameter of a few microns are used for recordings of rest.18–20 sympathetic neural outflow. A peripheral nerve is local- Muscle sympathetic activity does not correlate with ized by transcutaneous electrical stimulation (30–50 V, arterial pressure between different subjects as indicated 100–200 mA, 2 ms) evoking motor or sensory effects. by hypertensive patients with low MSA, hypotensive Afterward, a recording electrode is inserted intraneu- subjects with high MSA, and vice versa. Moreover, an rally, and a reference electrode is placed subcutaneously insulin-induced increase in MSA is not associated with a a couple of centimeters apart. A suitable electrode posi- change in arterial pressure.21 These observations suggest tion for intraneural recordings is found by minor adjust- that other variables exert major influences on the indi- ments of the electrode tip. The correct needle position is vidual level of arterial blood pressure and MSA.16,22,23 confirmed by a low threshold of intraneural electrical A relaxed subject at a comfortable ambient tempera- stimulation (0.2–1.0 V, 100–200 mA, 2 ms) evoking ture has virtually no detectable SSA.24–26 By exposing a muscle contractions or paresthesias as well as by record- subject to warm (43°) or cold (15°) environments, a ing of muscle (stretching of muscle tissue)– or cutaneous selective activation of either the sudomotor or the vaso- (light stroking or scratching of the skin)–derived affer- constrictor neural system is usually obtained, with sup- ent activity. Peak-to-peak amplitudes of multiunit raw pression of spontaneous activity in the other system.25,27 signals usually range from 10 to 20 ␮V, with a signal-to- In a comfortably warm subject, a deep spontaneous noise ratio of 3–5 to 1. The detected signal is amplified inspiration is followed by a strong increase of SSA, which (gain ϫ 50,000) and filtered (700- to 2,000-Hz band-pass consists of both sudomotor and vasoconstrictor activity.28,29 filter). To obtain a mean voltage neurogram, a resistance- Similarly, a sudden arousal stimulus elicits a burst of capacitance integrating circuit with a time constant of SSA24,25,30 whereas, in contrast, MSA is not affected by 0.1 s is used.12 The multiunit nerve recording is com- such stimuli.12,30 posed of several single nerve fiber discharges, which are With these findings, the traditional view of a whole- grouped. These groups can be counted as bursts in the body activation of sympathetic outflow in response to mean voltage neurogram. stimuli is no longer tenable, though striking correlations The mean amplitude or the area under the curve of between kidney, muscle, and cardiac sympathetic activ- single bursts in the integrated signal is dependent on the ity were observed at rest. Instead, it is suggested that the number of recorded single unit discharges (neural re- SNS has the capacity to selectively activate different cruitment) and also on the location of the needle relative subdivisions. This makes it difficult to generalize data to the nerve bundles. Therefore, slight movement may derived from one subdivision to other effector organs or alter the needle tip location within the nerve so that area conditions without direct experimental evidence. under the curve calculations should be analyzed cau- Therefore, microneurography is the only technique tiously. Finally, for the same reason, it is difficult to use available to directly assess sympathetic neural activity in these data on the same subject for comparisons between humans. Its advantage is the ability to detect rapid different days or experimental sessions.10,13 changes in nerve traffic. Accordingly, it is suitable to In peripheral nerves, efferent sympathetic activity
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