Effects of propofol and remifentanil on phrenic nerve activity and nociceptive cardiovascular responses in rabbits.

BACKGROUND: The effects of propofol, remifentanil, and their combination on phrenic nerve activity (PNA), resting heart rate (HR), mean arterial pressure (MAP), and nociceptive cardiovascular responses were studied in rabbits. METHODS: Basal anesthesia and constant blood gas tensions were maintained with alpha-chloralose and mechanical ventilation. PNA, HR, MAP, and maximum changes in HR and MAP (deltaHR, deltaMAP) evoked by electrical nerve stimulation of tibial nerves were recorded. The comparative effects were observed for propofol at infusion rates from 0.05 to 3.2 mg x kg(-1) x min(-1) (group I) and remifentanil from 0.0125 to 12.8 microg x kg(-1) x min(-1) alone (group II), and during constant infusions of propofol at rates of 0.1 and 0.8 mg x kg(-1) x min(-1) (groups III and IV, respectively). Finally, the effect of remifentanil on propofol blood levels was observed (group V). RESULTS: The infusion rates for 50% depression (ED50) of PNA, deltaHR, and deltaMAP were 0.41, 1.32, and 1.58 mg x kg-(1) x min(-1) for propofol, and 0.115, 0.125, and 1.090 microg x kg(-1) x min(-1) for remifentanil, respectively. The ratios for the ED50 values of deltaHR and deltaMAP to PNA were 3.2 and 3.9 for propofol, and 1.1 and 9.5 for remifentanil, respectively. Analysis of the expected and observed responses and isobologrms showed that although their combined effects on PNA, resting HR, and MAP, and deltaMAP were synergistic for deltaHR, they were merely additive. Remifentanil had no effect on propofol blood levels. CONCLUSION: PNA was abolished by propofol and remifentanil, alone and in combination, before significant depression of nociceptive pressor responses occurred. Their combined effects on PNA, HR, MAP, and deltaMAP are greater than additive, ie., synergistic. Unlike propofol, remifentanil obtunded pressor responses more than the resting circulation.     

胶体扩容对异氟醚-硬膜外阻滞复合麻醉时肝血流的影响

目的：探讨硬膜外阻滞复合异氟醚吸入全麻对血流动力学和肝血流的影响及其静脉输入3.5%尿素交连明胶（UG）的作用。方法：18只犬分两组，行胸段硬膜外阻滞后吸入0.5和1.0MAC异氟醚。实验组硬膜外阻滞前开始静脉输入UG12ml/kg。监测体循环、肺循环、肝动脉、门静脉血流动力学。肝血流用电磁血流仪测定。结果：对照组硬膜外阻滞后BP、HR、肝动脉阻力和门静脉血流均下降，加吸0.5MAC异氟醚使外周血管阻力（SVR）、肺动脉压和门静脉压降低；1.0MAC后心排血量下降、肝动脉血流也比0.5MAC时减少。心博量（SV）于吸入异氟醚后有所升高。实验组硬膜外阻滞后HR减慢、SV、增加而SVR下降，肝脏循环稳定。吸入异氟醚后全身和肝脏血流动力学变化显著轻于对照组。结论：硬膜外阻滞后，随异氟醚浓度升高，体循环、肺循环、肝动脉、门静脉血流动力学发生显著变化；胶体液扩容对比有明显的防治作用。     

Isoflurane depresses baroreflex control of heart rate in decerebrate rats

BACKGROUND: Isoflurane inhibits baroreflex control of heart rate (HR) by poorly understood mechanisms. The authors examined whether suprapontine central nervous system cardiovascular regulatory sites are required for anesthetic depression. METHODS: The effects of isoflurane (1 and 2 rat minimum alveolar concentration [MAC]) on the baroreflex control of HR were determined in sham intact and midcollicular-transected decerebrate rats. Intravenous phenylephrine (0.2-12 microg/kg) and nitroprusside (1-60 microg/kg) were used to measure HR responses to peak changes in mean arterial pressure (MAP). Sigmoidal logistic curve fits to HR-MAP data assessed baroreflex sensitivity (HR/MAP), HR range, lower and upper HR plateau, and MAP at half the HR range (BP50). Four groups (two brain intact and two decerebrate) were studied before, during, and after isoflurane. To assess sympathetic and vagal contributions to HR baroreflex, beta-adrenoceptor (1 mg/kg atenolol) or muscarinic (0.5 mg/kg methyl atropine) antagonists were administered systemically. RESULTS: Decerebration did not alter resting MAP and HR or baroreflex parameters. Isoflurane depressed baroreflex slope and HR range in brain-intact and decerebrate rats. In both groups, 1 MAC reduced HR range by depressing peak reflex tachycardia. Maximal reflex bradycardia during increases in blood pressure was relatively preserved. Atenolol during 1 MAC did not alter maximum reflex tachycardia. In contrast, atropine during 1 MAC fully blocked reflex bradycardia. Therefore, 1 MAC predominantly depresses sympathetic components of HR baroreflex. Isoflurane at 2 MAC depressed both HR plateaus and decreased BP50 in both groups. CONCLUSIONS: Isoflurane depresses HR baroreflex control by actions that do not require suprapontine central nervous system sites. Isoflurane actions seem to inhibit HR baroreflex primarily by the sympathetic nervous system.     

Isoflurane Depresses Baroreflex Control of Heart Rate in Decerebrate Rats

Background: Isoflurane inhibits baroreflex control of heart rate (HR) by poorly understood mechanisms. The authors examined whether suprapontine central nervous system cardiovascular regulatory sites are required for anesthetic depression.

Methods: The effects of isoflurane (1 and 2 rat minimum alveolar concentration [MAC]) on the baroreflex control of HR were determined in sham intact and midcollicular-transected decerebrate rats. Intravenous phenylephrine (0.2-12 [mu]g/kg) and nitroprusside (1-60 [mu]g/kg) were used to measure HR responses to peak changes in mean arterial pressure (MAP). Sigmoidal logistic curve fits to HR-MAP data assessed baroreflex sensitivity (HR/MAP), HR range, lower and upper HR plateau, and MAP at half the HR range (BP50). Four groups (two brain intact and two decerebrate) were studied before, during, and after isoflurane. To assess sympathetic and vagal contributions to HR baroreflex, [beta]-adrenoceptor (1 mg/kg atenolol) or muscarinic (0.5 mg/kg methyl atropine) antagonists were administered systemically.

Results: Decerebration did not alter resting MAP and HR or baroreflex parameters. Isoflurane depressed baroreflex slope and HR range in brain-intact and decerebrate rats. In both groups, 1 MAC reduced HR range by depressing peak reflex tachycardia. Maximal reflex bradycardia during increases in blood pressure was relatively preserved. Atenolol during 1 MAC did not alter maximum reflex tachycardia. In contrast, atropine during 1 MAC fully blocked reflex bradycardia. Therefore, 1 MAC predominantly depresses sympathetic components of HR baroreflex. Isoflurane at 2 MAC depressed both HR plateaus and decreased BP50 in both groups.     

Efficacy of simulated epinephrine-containing epidural test dose after intravenous atropine during isoflurane anesthesia in children

BACKGROUND AND OBJECTIVES: A double-blind, randomized study was performed to investigate heart rate (HR) and blood pressure responses to 2 doses of intravenous (IV) epinephrine (0.5 and 0.75 microg/kg) in 61 children, ages 3 months to 12 years. METHODS: Anesthesia was maintained with isoflurane (age-adjusted 1 minimal alveolar concentration [MAC]) in oxygen. All patients received IV atropine (10 microg/kg) and 5 minutes later were randomized to receive IV solutions (0.1 mL/kg) containing 1% lidocaine (n = 19, group I) with saline; lidocaine 1% with epinephrine 0.5 microg/kg (n = 21, group II); or lidocaine 1% with epinephrine 0.75 microg/kg (n = 21, group III). HR was recorded at 0, 15, 30, 45, 60, 90 seconds, and 2, 3, 4, and 5 minutes after test-dose injection. Systolic blood pressure (SBP), diastolic blood pressure, and end-tidal carbon dioxide were recorded at steady-state isoflurane anesthesia, after the injection of atropine, and at 45-second intervals after test-dose injections. RESULTS: Median maximum increases in HR were similar in groups II and III at 19 and 22 beats per minute (beats/min), respectively. An HR increase of > or =10 beats/min was observed in 19 of 21 patients who received 0.5 microg/kg epinephrine and 21 of 21 patients receiving 0.75 microg/kg. None of the patients in group I developed HR increases > or =10 beats/min. SBP increased > or =15 mm Hg in 17 of 21 patients in group II and 19 of 21 in group III. No dysrhythmias or T-wave amplitude change was noted. CONCLUSIONS: A simulated epidural test dose containing lidocaine 1 mg/kg with epinephrine 0.75 microg/kg, administered IV following atropine, may reliably increase HR to indicate unintentional injection into epidural vessels of children anesthetized with 1 MAC isoflurane.     

The Effects of Epidural Morphine on Cardiac and Renal Sympathetic Nerve Activity in [Greek small letter alpha]-Chloralose-anesthetized Cats

Background: Epidural morphine yields postoperative pain relief and hemodynamic stability. However, the effects of epidural morphine on sympathetic tone are unclear. This study was designed to elucidate the effects of epidural morphine on cardiac (CSNA) and renal (RSNA) sympathetic nerve activity by direct measurement in anesthetized cats.

Methods: Thirty mongrel cats anesthetized with [Greek small letter alpha]-chloralose were randomly assigned to one of the following five groups: control (0.2 ml/kg thoracic epidural normal saline; n = 5); thoracic epidural morphine (n = 9); lumbar epidural morphine (n = 6); vagotomized, sinoaortic denervated, thoracic epidural morphine (n = 5); or intravenous morphine (n = 5). Mean arterial pressure (MAP), heart rate (HR), CSNA, and RSNA were measured 0, 15, 30, 60, 90, and 120 min after saline or morphine (200 [micro sign]g/kg) administration and 15 min after reversal with 200 [micro sign]g naloxone given intravenously.

Results: In the control group, no changes in measured variables were found after either thoracic epidural saline or intravenous naloxone. Thoracic and lumbar epidural morphine both significantly reduced MAP, HR, CSNA, and RSNA 30 through 120 min after morphine administration (P < 0.05). These changes were reversed by intravenous naloxone. Changes after thoracic epidural morphine administration in vagotomized, baroreceptor-denervated cats were similar to those in intact cats. Intravenous morphine produced no significant changes except for a decrease in MAP, which was reversed by intravenous naloxone.     

Fentanyl Augments the Blockade of the Sympathetic Response to Incision (MAC-BAR) Produced by Desflurane and Isoflurane: Desflurane and Isoflurane MAC-BAR without and with Fentanyl

Background: Heart rate (HR) or mean arterial blood pressure (MAP) may increase in response to incision despite the absence of a motor response. The authors hypothesized that the MAC-BAR (minimum alveolar concentration of an anesthetic that blocks adrenergic response to incision) for isoflurane would exceed that for desflurane, and that fentanyl would decrease the MAC-BAR for each anesthetic in a dose-dependent manner.

Methods: Seventy-one patients were randomly allocated to one of six groups: desflurane or isoflurane without fentanyl or with 1.5 or 3 micro gram/kg fentanyl given intravenously 5 min before surgical incision. Anesthesia was induced with 2 mg/kg propofol given intravenously, and tracheal intubation facilitated with 0.1 mg/kg given intravenously. The first patient in each group received 1 MAC (end-tidal) of the inhaled anesthetic in 60% nitrous oxide (0.55 MAC), balance oxygen, maintained for at least 10 min before incision. The response was considered positive if the HR or MAP increased 15% or more. If the response was positive, the end-tidal concentration given to the next patient was 0.3 MAC greater; if the response was negative, the end-tidal concentration was 0.3 MAC less. The MAC-BAR level was calculated as the mean of four independent cross-over responses in each group.

Results: Desflurane and isoflurane anesthesia with 60% nitrous oxide did not change HR (P > 0.05) and decreased MAP (P < 0.05) before incision. Plasma epinephrine and norepinephrine concentrations after anesthesia and before incision were normal in all groups. The MAC-BAR level, without fentanyl, did not differ (P > 0.05) between desflurane (1.30 +/- 0.34 MAC [mean +/- SD]) and isoflurane (1.30 +/- 0.18 MAC). Fentanyl given at 1.5 micro gram/kg intravenously equivalently (P > 0.05) reduced the MAC-BAR for desflurane (to 0.40 +/- 0.18 MAC; P <0.05) and isoflurane (to 0.55 +/- 0.00 MAC; P < 0.05), but a further increase in fentanyl to 3 micro gram/kg caused no greater decrease in the MAC-BAR for desflurane (0.48 +/- 0.16 MAC) and isoflurane (0.40 +/- 0.30 MAC).     

Epidural lidocaine decreases sevoflurane requirement for adequate depth of anesthesia as measured by the Bispectral Index monitor

BACKGROUND: Epidural anesthesia potentiates sedative drug effects and decreases minimum alveolar concentration (MAC). The authors hypothesized that epidural anesthesia also decreases the general anesthetic requirements for adequate depth of anesthesia as measured by Bispectral Index (BIS). METHODS: After premedication with 0.02 mg/kg midazolam and 1 microg/kg fentanyl, 30 patients aged 20-65 yr were randomized in a double-blinded fashion to receive general anesthesia with either intravenous saline placebo or intravenous lidocaine control (1-mg/kg bolus dose; 25 microg x kg(-1) x min(-1)). A matched group was prospectively assigned to receive epidural lidocaine (15 ml; 2%) with intravenous saline placebo. All patients received 4 mg/kg thiopental and 1 mg/kg rocuronium for tracheal intubation. After 10 min of a predetermined end-tidal sevoflurane concentration, BIS was measured. The ED50 of sevoflurane for each group was determined by up-down methodology based on BIS less than 50 (MAC(BIS50)). Plasma lidocaine concentrations were measured. RESULTS: The MAC(BIS50) of sevoflurane (0.59% end tidal) was significantly decreased with lidocaine epidural anesthesia compared with general anesthesia alone (0.92%) or with intravenous lidocaine (1%; P < 0.0001). Plasma lidocaine concentrations in the intravenous lidocaine group (1.9 microg/ml) were similar to those in the epidural lidocaine group (2.0 microg/ml). CONCLUSIONS: Epidural anesthesia reduced by 34% the sevoflurane required for adequate depth of anesthesia. This effect was not a result of systemic lidocaine absorbtion, but may have been caused by deafferentation by epidural anesthesia or direct rostral spread of local anesthetic within the cerebrospinal fluid. Lower-than-expected concentrations of volatile agents may be sufficient during combined epidural-general anesthesia.     

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.     

Effect of xenon on autonomic cardiovascular control--comparison with isoflurane and nitrous oxide

STUDY OBJECTIVES: To clarify the effect of xenon on the autonomic nervous system by comparing similar effects of isoflurane and nitrous oxide.DESIGN: Prospective, randomized study.Setting: Operating room at a university hospital.PATIENTS: 39 ASA physical status I and II patients scheduled for general anesthesia. INTERVENTIONS: Patients were randomly allocated into one of three groups and received one of the following inhalational anesthetics: 56% of xenon (Group X), 0.94% of isoflurane (Group I), or 70% of nitrous oxide and 0.15% of isoflurane (Group N). Phenylephrine (pressor test) and nicardipine (depressor test) were given to assess baroreflex sensitivity.MEASUREMENTS AND MAIN RESULTS: Continuous blood pressure (BP) and electrocardiogram (ECG) were recorded before and during anesthesia to analyze heart rate (HR) variability and baroreflex sensitivity. Power spectrum of HR variability was calculated by fast Fourier transformation and power spectrum densities at low frequency (LF: 0.04-0.15Hz) and high frequency (HF: 0.15-0.40 Hz) were compared. Baroreflex sensitivity was calculated from the slope of regression for BP changes versus associated changes in R-R intervals. For HR variability, Group X showed lower power spectrum densities (ms(2).Hz(-1)) in LF and HF than did Group I (LF: 0.09 +/- 0.06 vs. 0.35 +/- 0.53; p < 0.05; HF: 0.40 +/- 0.34 vs. 0.98 +/- 0.68, p < 0.01). Group X had the lowest baroreflex sensitivity (ms.mmHg(-1)) via pressor test of the three study groups (Group X: 2.00 +/- 0.87, Group I: 3.53 +/- 2.14, Group N: 3.78 +/- 2. 17, p < 0.05).CONCLUSIONS: Xenon depressed both sympathetic and parasympathetic transmission more than isoflurane at 0.8 MAC. Xenon was also suggested to be relatively vagotonic.     

The effects of intravenous lidocaine administration on the minimum alveolar concentration of isoflurane in cats

Lidocaine decreases the minimum alveolar concentration (MAC) of inhaled anesthetics and has been used clinically to reduce the requirements for other anesthetic drugs. In this study we examined the effects of lidocaine on isoflurane MAC in cats. Six cats were studied. In Experiment 1, the MAC of isoflurane was determined. An IV bolus of lidocaine 2 mg/kg was then administrated and venous plasma lidocaine concentrations were measured to determine pharmacokinetic values. In Experiment 2, lidocaine was administered to achieve target plasma concentrations between 1 and 11 microg/mL and the MAC of isoflurane was determined at each lidocaine plasma concentration. Actual lidocaine plasma concentrations were 1.06 +/- 0.12, 2.83 +/- 0.39, 4.93 +/- 0.64, 6.86 +/- 0.97, 8.86 +/- 2.10, and 9.84 +/- 1.34 microg/mL for the target concentrations of 1, 3, 5, 7, 9, and 11 microg/mL, respectively. The MAC of isoflurane in this study was 2.21% +/- 0.17%, 2.14% +/- 0.14%, 1.88% +/- 0.18%, 1.66% +/- 0.16%, 1.47% +/- 0.13%, 1.33% +/- 0.23%, and 1.06% +/- 0.19% at lidocaine target plasma concentrations of 0, 1, 3, 5, 7, 9, and 11 microg/mL, respectively. Lidocaine, at target plasma concentrations of 1, 3, 5, 7, 9, and 11 microg/mL, linearly decreased isoflurane MAC by -6% to 6%, 7% to 28%, 19% to 35%, 28% to 45%, 29% to 53%, and 44% to 59%, respectively. We conclude that lidocaine decreases the MAC of isoflurane.     

Plasma lidocaine concentrations during continuous thoracic epidural anesthesia after clonidine premedication in children.

There is no report concerning oral clonidine's effects on epidural lidocaine in children. Therefore, we performed a study to assess the concentrations of plasma lidocaine and its major metabolite (monoethylglycinexylidide [MEGX]) in children receiving continuous thoracic epidural anesthesia after oral clonidine premedication. Ten pediatric patients, aged 1-9 yr, were randomly allocated to the Control or Clonidine 4 microg/kg group (n = 5 each). Anesthesia was induced and maintained with sevoflurane in oxygen and air (FIO2 40%). Epidural puncture and tubing were carefully performed at the Th11-12 intervertebral space. An initial dose of 1% lidocaine (5 mg/kg) was injected through a catheter into the epidural space, followed by 2.5 mg x kg(-1) x h(-1). Plasma concentrations of lidocaine and MEGX were measured at 15 min, 30 min, and every 60 min for 4 h after the initiation of continuous epidural injection. The concentrations of lidocaine and MEGX were measured using high-pressure liquid chromatography with ultraviolet detection. Hemodynamic variables were similar between members of the Control and Clonidine groups during anesthesia. The Clonidine group showed significantly smaller lidocaine concentrations (p < 0.05) and the concentration of MEGX tended to be smaller in the plasma of the Clonidine group for the initial 4 h after the initiation of epidural infusion. In conclusion, oral clonidine preanesthetic medication at a dose of 4 microg/kg decreases plasma lidocaine concentration in children. IMPLICATIONS: Oral clonidine decreases the plasma lidocaine concentration in children. Our finding may have clinical implications in patients receiving continuous epidural anesthesia. Additionally, perhaps an additional margin of safety regarding lidocaine toxicity is gained through the use of oral clonidine in children who will receive epidural lidocaine.     

Does epidural anesthesia have general anesthetic effects? A prospective, randomized, double-blind, placebo-controlled trial

BACKGROUND: Clinically, patients require surprisingly low end-tidal concentrations of volatile agents during combined epidural-general anesthesia. Neuraxial anesthesia exhibits sedative properties that may reduce requirements for general anesthesia. The authors tested whether epidural lidocaine reduces volatile anesthetic requirements as measured by the minimum alveolar concentration (MAC) of sevoflurane for noxious testing cephalad to the sensory block. METHODS: In a prospective, randomized, double-blind, placebo-controlled trial, 44 patients received 300 mg epidural lidocaine (group E), epidural saline control (group C), or epidural saline-intravenous lidocaine infusion (group I) after premedication with 0.02 mg/kg midazolam and 1 microg/kg fentanyl. Tracheal intubation followed standard induction with 4 mg/kg thiopental and succinylcholine 1 mg/kg. After 10 min or more of stable end-tidal sevoflurane, 10 s of 50 Hz, 60 mA tetanic electrical stimulation were applied to the fifth cervical dermatome. Predetermined end-tidal sevoflurane concentrations and the MAC for each group were determined by the up-and-down method and probit analysis based on patient movement. RESULTS: MAC of sevoflurane for group E, 0.52+/-0.18% (+/- 95% confidence interval [CI]), differed significantly from group C, 1.18+/-0.18% (P < 0.0005), and from group I, 1.04+/-0.18% (P < 0.001). The plasma lidocaine levels in groups E and I were comparable (2.3+/-1.0 vs. 3.0+/-1.2 microg/ml +/- SD). CONCLUSIONS: Lidocaine epidural anesthesia reduced the MAC of sevoflurane by approximately 50%. This MAC sparing is most likely caused by indirect central effects of spinal deafferentation and not to systemic effects of lidocaine or direct neural blockade. Thus, lower concentrations of volatile agents than those based on standard MAC values may be adequate during combined epidural-general anesthesia.     

比较硬膜外阻滞复合安氟醚或异氟醚对肝血流及氧代谢的影响

目的 探讨硬膜外阻滞与安氟醚或异氟醚吸入复合麻醉对血流动力学,肝血流及代谢的影响。方法 选用健康杂种犬２０只行胸段硬膜外阻滞后分为两缚,分别吸入,０．５和１．０ＭＡＣ安氟醚或异氟醚,监测麻醉前后体循环,肝动脉,门静脉血流动力及肝脏氧供,氧耗。结果 硬膜外阻滞后血压,门静脉血流和氧供下降,加吸安氟醚０．５ＭＡＣ使心排血量也下降,１．０ＭＡＣ后肝动脉血流及氧供也减少,加吸异氟醚０．５ＭＡＣ心排血量稳定     

Desflurane-mediated Sympathetic Activation Occurs in Humans Despite Preventing Hypotension and Baroreceptor Unloading

Background: Increasing concentrations of desflurane result in progressive decreases in blood pressure (BP) and, unlike other currently marketed, potent volatile anesthetics, heightened sympathetic nervous system activity. This study aimed to determine whether baroreflex mechanisms are involved in desflurane-mediated sympathetic excitation.

Methods: Healthy volunteers were anesthetized with desflurane (n = 8) or isoflurane (n = 9). Heart rate (HR; measured by electrocardiograph), blood pressure (BP; measured by arterial catheter), and efferent sympathetic nerve activity (SNA; obtained from percutaneous recordings from the peroneal nerve) were monitored. Baroreflex sensitivity was evaluated at baseline while volunteers were conscious and during 0.5, 1, and 1.5 minimum alveolar concentration (MAC) anesthesia via bolus injections of nitroprusside (100 micro gram) and phenylephrine (150 micro gram) to decrease and increase BP. To prevent the BP decline with increasing depths of anesthesia, phenylephrine was infused to maintain mean BP at the 0.5 MAC level.

Results: The HR, BP, and SNA were similar between the groups at the conscious baseline measurement. Efferent SNA did not change during higher MAC of isoflurane, but it increased progressively as desflurane concentrations were increased beyond 0.5 MAC, despite maintaining BP at the 0.5 MAC value with phenylephrine infusions (P < 0.05). Cardiac baroslopes (based on changes in HR) were progressively and similarly decreased with increasing concentrations of isoflurane and desflurane (P < 0.05). Sympathetic baroslopes (based on SNA) decreased with increasing isoflurane concentrations but were maintained with increasing concentrations of desflurane; the response was significantly different between groups.     

Hemodynamic Responses to Intravascular Injection of Epinephrine-containing Epidural Test Doses in Adults during General Anesthesia

Background: Epidural anesthesia is sometimes initiated during general anesthesia, yet few data exist concerning efficacy of epinephrine-containing test doses.

Methods: Thirty-six patients were randomized to receive either 0.5 MAC isoflurane, 1 MAC isoflurane, or 0.5 MAC each (1 MAC total) of isoflurane and nitrous oxide. Each subject received intravenous saline followed by three test doses containing 45 mg lidocaine with 7.5, 15, and 30 micro gram epinephrine in a randomized, double-blind fashion. Heart rate and systolic, diastolic, and mean blood pressures were measured for 5 min after injection. Positive hemodynamic criteria identifying intravascular injection were determined from peak increases in hemodynamics during administration of saline. Dose-effect relationships between epinephrine and peak increases in hemodynamics were assessed with linear regression. Minimum required doses of epinephrine to produce peak positive hemodynamic increases on average were determined from linear regression.

Results: Positive hemodynamic criteria were identified as increases in heart rate greater or equal to 8 beats/min, systolic blood pressure greater or equal to 13 mmHg, diastolic blood pressure greater or equal to 7 mmHg, and mean blood pressure greater or equal to 9 mmHg. Significant dose-effect relationships were observed for epinephrine and peak increases in hemodynamics (correlation coefficients ranged from 0.61-0.91). Minimum required doses of epinephrine ranged from 6 to 19 micro gram depending on hemodynamic measurement and anesthetic group.     

Isoflurane attenuates baroreflex control of heart rate in human neonates

Clinical studies have suggested that baroreflex regulation of heart rate may be more affected by inhalational anesthetics in human neonates or young animals than in adults. To test this hypothesis, baroreceptor reflex control of heart rate was studied in eight neonates during administration of 1 MAC isoflurane. The neonates were hemodynamically stable and their lungs were mechanically ventilated. No other anesthetic was used. Mean (+/- SD) corrected gestational age was 39.4 +/- 2.0 weeks and mean weight was 2,710 +/- 430 g. The pressor response was tested with the use of phenylephrine and the depressor response with nitroglycerin. Changes in heart rate (R-R interval) were plotted against the changes in systolic arterial pressure, and the slope of the linear portion of this relationship was used to define the baroreflex response. Both baroresponses measured in awake neonates varied widely between patients. With administration of approximately 1 MAC isoflurane, the pretest mean systolic arterial pressure decreased by about 30% (P less than 0.001), whereas mean heart rate values remained unchanged compared with control awake values. During isoflurane administration, the mean (+/- SD) pressor response decreased to 23% of control awake values (11.2 +/- 7.7 ms/mmHg vs. 2.6 +/- 3.7 ms/mmHg; P less than 0.01) and the depressor response to 28% of control (4.3 +/- 3.2 ms/mmHg vs. 1.2 +/- 0.8 ms/mmHg; P less than 0.05). These changes can be attributed to a significant resetting of heart rate itself (calculated as the change in R-R interval at a constant pressure).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Oral Clonidine on Heart Rate Changes after Neostigmine-Atropine Administration

Background: Clonidine reduces heart rate (HR) responses to atropine, whereas neostigmine causes bradycardia. This study was designed to determine whether clonidine premedication would reduce tachycardia after neostigmine-atropine administration.

Methods: Fifty adult patients without cardiovascular disorders who were schedule for elective surgeries were randomly assigned to receive approximately 5 [micro sign]g/kg (oral clonidine clonidine group, n = 25) or no clonidine (control group, n = 25) 90 min before induction of general anesthesia. After tracheal intubation, anesthesia was maintained with N2 O and 1-2% isoflurane in oxygen while patients were paralyzed with vecuronium and mechanically ventilated. When surgeries were completed, adequate spontaneous respiration, responses to verbal commands, and sustained tetanus by stimulating the ulnar nerve were confirmed, and patients' tracheas were extubated. Then a mixture of 0.05 mg/kg neostigmine and 0.02 mg/kg atropine was administered intravenously over 20 s under stable hemodynamic condition (systolic blood pressure and HR within +/- 5% of preceding values), and blood pressure and HR were measured noninvasively at 1-min intervals for 10 min.

Results: Increases in HR in the clonidine group were significantly less 1-4 min after neostigmine-atropine injections compared with HR values in the control group. A maximum increase in HR of the clonidine group was also significantly less than the control group (15 +/- 7 vs. 23 +/- 10 beats/min; means +/- SD), whereas absolute values of mean blood pressure were similar. Severe bradycardia (HR < 50 beats/min) developed in no patients in either group.     

Supraspinal pupillary effects of intravenous and epidural fentanyl during isoflurane anesthesia

BACKGROUND AND OBJECTIVES: Epidural fentanyl has been shown to gain rapid access to the circulation resulting in supraspinal effects. We compared the supraspinal effects of fentanyl via epidural versus intravenous (IV) routes, during isoflurane anesthesia. Supraspinal fentanyl effect was evaluated as a reduction of pupillary reflex dilation (PRD) measured with infrared pupillometry. METHODS: Eighteen patients undergoing abdominal procedures were studied during combined epidural and general anesthesia. General anesthesia was provided by 0.55 to 0.70% end-tidal isofurane in air:oxygen (50:50). Sensory block of the surgical field was established with bupivacaine 0.375% and confirmed by absence of PRD to cutaneous stimulation. A high cervical dermatome was then stimulated (60 to 70 mA) at 5-minute intervals via cutaneous needle electrodes, and PRD was measured with each stimulation, using infrared pupillometry. Baseline PRD was determined and then a randomized injection of cpidueral saline (n = 6), epidural fentanyl 3 microg/kg (n = 6), or IV fentanyl 3 microg/kg (n = 6) was given. Subsequently, PRD was measured at 5, 10, 20, 30, 40, 60, and 80 minutes. Maximum change in PRD and time to maximum change were calculated for each group. RESULTS: Following epidural injection, suppression of PRD was highly variable among subjects. The maximum suppression was 70+/-15% at 23.3+/-10.3 minutes for the epidural group and 96+/-3% at 10.8+/-7.4 min for the IV group (P<.0001). Epidural saline produced no effect. CONCLUSIONS: Supraspinal effects of epidural fentanyl can be assessed during general anesthesia using infrared pupillometry. Epidural fentanyl 3 microg/kg produces significant but variable supraspinal effects during 0.5 minimum alveolar concentration isoflurane anesthesia.     

Propofol anesthesia enhances pressor response to ephedrine in patients given clonidine.

We studied the hemodynamic effects of ephedrine in patients with or without clonidine premedication during either isoflurane or propofol anesthesia. Forty adult patients were randomly assigned to one of two groups: 20 patients received famotidine 20 mg orally (control group) and 20 received clonidine 3 microg/kg and famotidine 20 mg orally (clonidine group). Within each group, 10 patients were then anesthetized with isoflurane and 10 with propofol. Hemodynamic measurements were taken at 1-min intervals for 10 min after a bolus injection of ephedrine 0.1 mg/kg. The magnitude of the maximal pressor response to ephedrine was no different whether patients without clonidine were anesthetized with isoflurane (increase 5+/-7 mm Hg) or propofol (3+/-9 mm Hg); however, this response was greater (P<0.05) with propofol (17+/-6 mm Hg) versus isoflurane (6+/-5 mm Hg) in patients given clonidine. The arterial blood pressure increase in clonidine-premedicated patients with propofol anesthesia was the largest among the four subgroups. The heart rate response to ephedrine was not significant in patients anesthetized with isoflurane and was small but significant in those anesthetized with propofol. The present results, together with previous studies on the effect of ephedrine in patients medicated with clonidine, suggest that the interaction between clonidine and ephedrine is modulated by the anesthetic used. IMPLICATIONS: We evaluated the pressor response to ephedrine during isoflurane or propofol anesthesia with or without clonidine premedication. Our study suggests that, in anesthetized patients premedicated with clonidine, decreases in blood pressure may be easier to reverse with ephedrine with some types of anesthesia (e.g., propofol) than with others (e.g., isoflurane).