Michael Muzi

Sympathetic Responses to Induction of Anesthesia in Humans with Propofol or Etomidate

Anesthetic induction with propofol commonly results in hypotension. This study explored potential mechanisms contributing to hypotension by recording cardiovascular responses including sympathetic neural activity from patients during induction of anesthesia with propofol (2.5 mg.kg-1 plus 200 micrograms.kg-1.min-1) or, for comparison, etomidate (0.3 mg.kg-1 plus 15 micrograms.kg-1.min-1). Twenty-five consenting, nonpremedicated, ASA physical status 1 and 2, surgical patients were evaluated. Measurements of R-R intervals (ECG), blood pressure (radial artery), forearm vascular resistance (plethysmography), and efferent muscle sympathetic nerve activity ([MSNA] microneurography: peroneal nerve) were obtained at rest and during induction of anesthesia. In addition, a sequential bolus of nitroprusside (100 micrograms) followed by phenylephrine (150 micrograms) was used to obtain data to quantitate the baroreflex regulation of cardiac function (R-R interval) and sympathetic outflow (MSNA) in the awake and anesthetized states. Etomidate induction preserved MSNA, forearm vascular resistance, and blood pressure, whereas propofol reduced MSNA by 76 +/- 5% (mean +/- SEM), leading to a reduction in forearm vascular resistance and a significant hypotension. Both cardiac and sympathetic baroslopes were maintained with etomidate but were significantly reduced with propofol, especially in response to hypotension. These findings suggest that propofol-induced hypotension is mediated by an inhibition of the sympathetic nervous system and impairment of baroreflex regulatory mechanisms. Etomidate, conversely, maintains hemodynamic stability through preservation of both sympathetic outflow and autonomic reflexes.

Sympathetic Hyperactivity during Desflurane Anesthesia in Healthy Volunteers: A Comparison with Isoflurane

Background:Desflurane has been reported to produce more tachycardia and hypertension on induction than isoflurane. The present study employed microneurography to determine whether these cardiovascular effects were related to sympathetic outflow. Methods:In 14 healthy, young (age 20–31 yr) volunteers, arterial pressure was measured from the radial artery, forearm blood flow was derived by strain gauge plethysmography, and sympathetic nerve activity (SNA) directed to skeletal muscle blood vessels was recorded from a tungsten needle placed percutaneously into the peroneal nerve. Heart rate, blood pressure, muscle SNA, respiration, tidal volume, end-tidal carbon dioxide, and desflurane or isoflurane concentrations (infrared spectroscopy) were continuously monitored before and during anesthesia. Two minutes after administering thiopental (5 mg/kg) and vecuronium (0.2 mg/kg), desflurane (n = 7) or isoflurane (n = 7) was titrated gradually to the inspired gas over several minutes to 1.5 MAC. Results:The initiation of desflurane anesthesia resulted in significant changes that included a 2.5-fold increase in SNA, hypertension (peak mean arterial pressure 114 ± 3 mmHg), tachycardia (peak heart rate 102 ± 6 beats/min), facial flushing, and tearing. Moderate upper airway obstruction developed in three subjects approximately 4 min after initiating desflurane, despite neuromuscular blockade. These responses were not observed in subjects receiving isoflurane. After tracheal intubation, the anesthetic concentration was maintained at 0.5 MAC for 30 min. Steady-state measurements of hemodynamics and SNA were obtained. Similar steady-state measurements were obtained 15 min after establishing 1.0 and 1.5 MAC. Both anesthetics produced a progressive reduction in blood pressure and forearm vascular resistance, and muscle SNA gradually increased. In subjects receiving desflurane, heart rate remained unchanged until the 1.5-MAC level was reached, at which time tachycardia (a 10-beat/min increase) was noted. The transition from 1.0 to 1.5 MAC desflurane resulted in significant heart rate increases (>30 beats/min), hypertension (>30 mmHg), and a doubling of SNA that persisted for several minutes. These responses did not occur in the isoflurane group. Conclusions:Titration of desflurane following thiopental induction and increasing the concentration of desflurane from 1.0 to 1.5 MAC result in sympatho-excitation, hypertension and tachycardia in healthy, young volunteers. Until methods are determined to attenuate these responses, desflurane should be administered with great caution to patients who may be placed at risk by these responses.

Mechanisms whereby propofol mediates peripheral vasodilation in humans : Sympathoinhibition or direct vascular relaxation ?

Background Anesthetic induction and maintenance with propofol are associated with decreased blood pressure that is, in part, due to decreased peripheral resistance. Several possible mechanisms whereby propofol could reduce peripheral resistance include a direct action of propofol on vascular smooth muscle, an inhibition of sympathetic activity to the vasculature, or both. This study examined these two possibilities in humans by measuring the forearm vascular responses to infusions of propofol into the brachial artery (study 1) and by determining the forearm arterial and venous responses to systemic (intravenous) infusions of propofol after sympathetic denervation of the forearm by stellate blockade (study 2). Methods Bilateral forearm venous occlusion piethysmography was used to examine forearm vascular resistance (FVR) and forearm vein compliance (FVC). Study 1 used infusion of intralipid (time control) and propofol at rates between 83 and 664 micro gram/min into the brachial artery of 11 conscious persons and compared responses to arterial infusions of sodium nitroprusside (SNP) at 0.3, 3.0, and 10 micro gram/min. Venous blood from the infusion arm was assayed for plasma propofol concentrations. In study 2, after left stellate block (12 ml 0.25% bupivacaine + 1% lidocaine), six participants were anesthetized and maintained with propofol infusions of 125 and 200 micro gram [centered dot] kg sup ‐1 [centered dot] min sup ‐1. Simultaneous right forearm (unblocked) blood flow dynamics served as the time control. In three additional conscious participants, intrabrachial artery infusions of SNP and nitroglycerin, both at 10 micro gram/min, were performed before and after stellate blockade of the left forearm to determine whether the sympathetically denervated forearm vessels could dilate beyond the level produced by denervation alone. Results In study 1, infusion of intralipid or propofol into the brachial artery did not change FVR or FVC. Sodium nitroprusside significantly decreased FVR in a dose‐dependent manner by 22 +/‐ 5%, 65 +/‐ 3%, and 78 +/‐ 2% (mean +/‐ SEM) but did not change FVC. During the incremental propofol infusions, plasma propofol concentrations increased from 0.2 to 10.1 micro gram/ml and averaged 7.4 +/‐ 1.1 micro gram/ml during the highest infusion rate. In study 2, stellate ganglion blockade decreased FVR by 50 +/‐ 6% and increased FVC by 58 +/‐ 10%. Propofol anesthesia at 125 and 200 micro gram [centered dot] kg sup ‐1 [centered dot] min sup ‐1 progressively reduced mean arterial pressure. In the arm with sympathetic denervation, FVR and FVC showed no further changes during propofol anesthesia, whereas in the control arm FVR significantly decreased by 41 +/‐ 9% and 42 +/‐ 7%, and FVC increased significantly by 89 +/‐ 27% and 85 +/‐ 32% during 125 and 200 micro gram [centered dot] kg sup ‐1 [centered dot] min sup ‐1 infusions of propofol, respectively. In the three additional conscious participants, intraarterial infusion of SNP and nitroglycerin (TNG) after the stellate blockade resulted in a further decrease of FVR and a further increase of FVC. Conclusions In contrast to SNP infusions, propofol infusions into the brachial artery of conscious persons caused no significant vascular responses, despite the presence of therapeutic plasma concentrations of propofol within the forearm. The effects of propofol anesthesia on FVR and FVC are similar to the effects of sympathetic denervation by stellate ganglion blockade. Thus the peripheral vascular actions of propofol appear to be due primarily to an inhibition of sympathetic vasoconstrictor nerve activity.

Venodilation contributes to propofol-mediated hypotension in humans

The present investigation explored the possibility that the commonly observed hypotension that occurs during induction of anesthesia with propofol might be related to its ability to produce venodilation. Thirty-six ASA I and II patients who received no premedication were studied. The first 20 patients were divided into two equal groups. Hemodynamic measurements consisted of heart rate, arterial blood pressure, and forearm venous compliance by occlusive plethysmography. Baseline measurements were made in awake patients while resting in a supine position. Repeat measurements were made during steady-state infusions of propofol (2.5 mg/kg bolus injection, followed by a continuous infusion at 200 μg·kg−1·min−1) or thiopental (4 mg/kg bolus injection, followed by continuous infusion at 200 μg·kg−1·min−1), 10 min after tracheal intubation while patients were artificially ventilated. Both anesthetics resulted in a significant (P <0.05) and similar tachycardia; however, propofol produced significant decreases in systolic (−30 ± 9 mm Hg) and diastolic (−11 ± 4 mm Hg) arterial blood pressure. Forearm venous compliance was significantly increased during propofol administration but unchanged in patients receiving thiopental. In four additional patients receiving smaller consecutive infusions of propofol (50 and 100 μg·kg−1·min−1), significant subtle increases in forearm compliance were also recorded. These increases were not observed in four patients who received placebo infusions. Thus, one mechanism promoting hypotension during propofol anesthesia in humans seems to be related to its direct effects on venous smooth muscle tone and presumably venous return.

Neurocirculatory responses to sevoflurane in humans : a comparison to desflurane

Background Sevoflurane and desflurane are new volatile anesthetics with low blood solubilities that confer properties of rapid anesthetic induction and emergence. Desflurane has been associated with neurocirculatory excitation after the rapid increase in inspired concentrations. The current study evaluated and compared the sympathetic and hemodynamic responses associated with the administration of sevoflurane to those associated with administration of desflurane in humans.

Induction of Anesthesia and Tracheal Intubation with Sevoflurane in Adults

BackgroundThe speed, quality, and cost of mask induction of anesthesia and laryngeal mask airway insertion or tracheal intubation were studied in young non-premedicated volunteers given high inspired concentrations of sevoflurane (6 to 7%).MethodsTwenty healthy persons who were 19 to 32 years old pa

Clonidine Reduces Sympathetic Activity but Maintains Baroreflex Responses in Normotensive Humans

Clonidine, an alpha 2-adrenergic agonist, has been shown to modify the hemodynamic responses to surgery. To examine further the mechanism underlying this action, we evaluated the neurocirculatory effects of oral clonidine and the ability of clonidine to alter the hemodynamic and sympathetic responses to a noxious stimulus (cold pressor test) and to baroreceptor perturbations in nine healthy men (ages 20-29 yr). Heart rate (ECG), blood pressure (radial artery catheter), central venous pressure (jugular vein), and cardiac output (impedance cardiography) were monitored before and after oral clonidine (0.3 mg) or placebo. Plasma norepinephrine was measured with high-performance liquid chromatography. Sympathetic nerve activity (SNA) to skeletal muscle blood vessels was recorded from a Tungsten needle positioned within the peroneal nerve. Baroreceptor testing was carried out by intravenous bolus injections of nitroprusside (100 micrograms) followed 60 s later by intravenous phenylephrine (150 micrograms). The slope of the linear relationship between the change in R-R interval versus the change in mean pressure (cardiac baroslope) or change in SNA versus change in diastolic pressure (sympathetic baroslope) was determined at baseline and 75 min after clonidine or placebo. In addition, peak responses to the cold pressor test (60-s hand immersion in ice water) were determined at the same intervals. Clonidine progressively decreased blood pressure and muscle SNA over the 75-min session. Clonidine subtly reduced the sympathoexcitation produced by the cold pressor test but did not alter the gain of the baroreceptor reflex regulating cardiac interval or peripheral SNA; baroslope relationships were simply shifted leftward (to operate at lower pressures).(ABSTRACT TRUNCATED AT 250 WORDS)

Propofol and autonomic reflex function in humans.

The effects of continuous infusions of propofol on baroreceptor reflex regulation of cardiac rate and peripheral sympathetic nerve activity were evaluated in seven healthy, normotensive, young (19‐26 yr), male volunteers. Heart rate, radial artery pressure, and continuous recordings of efferent sympathetic vasoconstrictor outflow (from the peroneal nerve) were monitored. Baroreceptor perturbations were produced by bolus intravenous injections of nitroprusside (100 μg) followed 60 s later by phenylephrine (150 μg). These stimuli were delivered to subjects while conscious and during propofol anesthesia (200 μg‐kg‐1min‐1) at least 25 min after subjects were paralyzed (vecuronium), had tracheas intubated, and were ventilated (30% O2:70% N2) to maintain normocarbia. Additional data were collected during hypercarbic conditions and during a lower infusion rate of propofol (100 μg.kg‐1.min‐1) combined with 70% nitrous oxide. Propofol infusions significantly lowered sympathetic nerve activity (SNA) and blood pressure (BP) and increased heart rate (HR). Cardiac baroreceptor sensitivity determined during nitroprusside was reduced 60% during propofol infusions and was only subtly improved during simultaneous N2O administration. In contrast, reflex sensitivity during phenylephrine was not changed from awake values during each of the three experimental conditions. Reflex regulation of SNA was nearly abolished during normocarbic conditions under propofol anesthesia but restored to conscious levels during hypercarbia and during N2O administration. These data indicate that propofol markedly attenuates reflex responses to hypotension, but that reflex sympathetic responses are better maintained in hypercarbic conditions and when lower doses of propofol are used in conjunction with N2O. In contrast, reflex responses to a hypertensive stimulus seem to be well preserved during propofol infusions regardless of the prevailing Paco2 or the presence of N2O.

A Comparison of Baroreflex Sensitivity during Isoflurane and Desflurane Anesthesia in Humans

Background Desflurane anesthesia has been associated with heart rate (HR) and sympathetic nerve activity (SNA) responses that differ from those during isoflurane anesthesia. Whether these differences might be due to better preservation by desflurane of the baroreceptor reflex control of HR or SNA in humans was examined. Methods Baroreflex sensitivity was assessed in 18 volunteers anesthetized with either desflurane or isoflurane. Measurements of HR, blood pressure (BP), and efferent SNA (percutaneous recordings from the peroneal nerve) were made, and baroreflex sensitivity was evaluated at conscious baseline and during 0.5, 1.0, and 1.5 MAC anesthesia. Baroreflex responses were triggered by bolus intravenous injections of nitroprusside (100 micro gram) and phenylephrine (150 micro gram). The linear portions of the baroreflex curves relating HR to mean arterial pressure and relating SNA to diastolic pressure were determined to obtain cardiac and sympathetic baroslopes, respectively. Results Cardiac (HR) baroslopes were equally diminished at increasing MAC of both anesthetics. Sympathetic baroslopes were preserved at 0.5 MAC isoflurane but diminished at 0.5 MAC desflurane. Higher MAC produced equal depression of sympathetic baroslopes with both anesthetics. Conclusions Increasing MAC of desflurane and isoflurane anesthesia results in similar and progressive decreases in BP but dissimilar SNA and HR responses. These differences are not explained by disparate effects of these anesthetics on the baroreceptor reflex control of SNA or HR.

Site(s) Mediating Sympathetic Activation with Desflurane

Background Three strategies were employed to better define the afferent site(s) at which desflurane initiates its neurocirculatory activation. Methods Young (aged 19–28 yr) healthy volunteers were employed in three separate studies. Monitoring included electrocardiography, radial artery blood pressure, and direct recordings of sympathetic outflow to skeletal muscle blood vessels by microneurography. In each study, anesthesia was established with 2.5 mg/kg propofol, and in studies 1 and 2 was maintained with 5.4% desflurane via a double‐lumen tube. In study 1 (n = 7) a double‐lumen tube was placed with the bronchial cuff just below the vocal cords to selectively give 14.5% desflurane or 2.4% isoflurane to the upper airway (via the tracheal lumen) or lower airway (via the bronchial lumen). Study 2 (n = 14) consisted of standard placement of a left side double‐lumen tube to selectively increase the inspired desflurane concentration of either right or left lung to 11% while decreasing the inspired concentration in the opposite lung to 0%, thereby maintaining constant systemic concentrations of desflurane (gas chromatography). Study 3 consisted of lidocaine or placebo airway treatment before anesthetic induction and administration of 11% inspired desflurane by mask: group A‐‐n = 9, topical and nebulized lidocaine, glossopharyngeal and superior laryngeal nerve blocks, and transtracheal administration of lidocaine; group B‐‐n = 7, similar treatment as group A with placebo (saline); and group C‐‐n = 8, systemic infusions of 2% lidocaine to match plasma concentrations of lidocaine in group A. Results In study 1, significant increases in heart rate, mean arterial pressure, and sympathetic neural activity (26%, 23%, and 62%, respectively) occurred when desflurane was directed to the upper airway. These responses were approximately twofold to sixfold larger when desflurane was given to the lower airway (lungs). There were no significant increases in these variables when isoflurane was administered to the upper airways, and a significant increase in heart rate occurred only when isoflurane was delivered to the lower airways. In study 2, separate right or left lung increases in desflurane did not change the blood concentration of desflurane or sympathetic neural activity but led to significant increases in heart rate (44%) and mean arterial pressure (32%). The simultaneous administration of desflurane to both lungs increased the millimolar (mM) concentration of desflurane in the blood from 1.17 to 2.39 mM and led to increases in sympathetic neural activity (750%), heart rate (90%), and mean arterial pressure (63%). In study 3, neither regional nor systemic administration of lidocaine reduced the significant neurocirculatory activation caused by the rapid increase in the inspired concentration of desflurane by mask. Conclusions There are sites in the upper airway (larynx and above) that respond with sympathetic activation during rapid increases in desflurane concentration independent of systemic anesthetic changes. These responses, while lesser than those seen with rapid increases to the lung, may represent direct irritation of airway mucosa. Heart rate and mean arterial pressure responses to desflurane can be initiated by selectively increasing concentrations to either right or left lung without altering systemic levels of desflurane. From this it is inferred that there are sites within the lungs, separate from systemic sites, that mediate this response. Neither systemic lidocaine nor attempted blockade of upper airway sites with cranial nerve blocks combined with topical lidocaine was effective in attenuating the neurocirculatory activation associated with desflurane.