Propofol does not inhibit hypoxic pulmonary vasoconstriction in humans

The influence of increasing doses of propofol (from 6 to 12 mg/kg/h by continuous infusion) on hypoxic pulmonary vasoconstriction was studied in 10 patients prior to thoracic surgery. All patients were intubated with a left-sided double-lumen endobronchial tube. Initial anesthesia and muscle relaxation were accomplished by administering fentanyl, droperidol, and pancuronium. After 100% oxygen ventilation of both lungs for 20 min in a lateral decubitus position, the nondependent lung was deflated and one-lung ventilation was started. The dependent lung was continuously ventilated with 100% oxygen. Twenty minutes after the start of one-lung ventilation, propofol at an IV infusion rate of 6 mg/kg/h was added to the anesthetic technique. Thirty minutes later it was increased to 10 mg/kg/h and another 15 min later to 12 mg/kg/h. Then the propofol infusion was stopped. Thirty minutes later, two-lung ventilation was restarted to compare initial values. No changes in venous admixture or PaO2 were observed during propofol infusion. There was no change in any respiratory or circulatory variables except systemic vascular resistance, which decreased significantly immediately after the propofol infusion commenced but returned to control values 15 min later for the rest of the observation period. After reestablishing two-lung ventilation, all variables did not differ from control values. In all patients, the hypoxic pulmonary vasoconstriction reflex was present after institution of one-lung ventilation and was not abolished after administration of propofol in doses from 6 to 12 mg/kg/h.     

High thoracic epidural anesthesia does not inhibit sympathetic nerve activity in the lower extremities.

BACKGROUND: Sympathetic nerve activity was recorded in the leg during high thoracic epidural anesthesia with a segmental sensory blockade of the upper thoracic dermatomes to test the hypothesis that the sympathetic blockade accompanying thoracic epidural anesthesia includes caudal parts of the sympathetic nervous system. METHODS: Experiments were performed on 10 patients scheduled for thoracotomy. An epidural catheter was inserted at the T3-T4 or T4-T5 interspace. In the main protocol (seven patients), blood pressure, heart rate, and skin temperature (big toe, thumb) were continuously monitored, and multiunit postganglionic sympathetic nerve activity was recorded with a tungsten microelectrode in a muscle-innervating fascicle of the peroneal nerve. After baseline data collection, muscle sympathetic nerve activity was recorded for an additional 45-min period after epidural injection of 4-6 ml bupivacaine, 5 mg/ml. In an additional three patients, the effects of thoracic epidural anesthesia on skin-innervating sympathetic nerve activity were qualitatively assessed. RESULTS: Activation of thoracic epidural anesthesia caused no significant changes in peroneal muscle sympathetic nerve activity (n = 7), blood pressure, or heart rate. Skin temperature increased significantly in the hand 15 min after activation of the blockade, from 32.7 +/- 2.4 degrees C to 34.4 +/- 1.5 degrees C (mean +/- SD), whereas no changes were observed in foot temperature. The sensory blockade extended from T1 (C4-T2) to T8 (T6-T11). CONCLUSIONS: A high thoracic epidural anesthesia with adequate sensory blockade of upper thoracic dermatomes may be achieved without blockade of caudal parts of the sympathetic nervous system. This finding differs from that of earlier studies that used indirect methods to evaluate changes in sympathetic nerve activity.     

Epinephrine does not reduce the plasma concentration of lidocaine during continuous epidural infusion in children

PURPOSE: During continuous epidural anesthesia with lidocaine, plasma monoethylglycinexylidide (MEGX), an active metabolite of lidocaine, increases continuously. We assessed the effect of epinephrine on the absorption of lidocaine and the accumulation of MEGX during continuous epidural anesthesia in children. METHODS: Anesthesia was administered as an initial bolus of 5 mg x kg(-1) of 1% lidocaine solution followed by continuous infusion at 2.5 mg x kg(-1) x hr(-1). Patients in the control group (n = 8) received lidocaine alone, while patients in the epinephrine group (n = 8) received lidocaine + epinephrine (5 microg x mL(-1)). Concentrations of lidocaine and its active metabolite, MEGX, were measured in plasma samples obtained after 15 min, 30 min, and one, two, three, four, and five hours of infusion using high-performance liquid chromatography with ultraviolet detection. RESULTS: Plasma lidocaine concentrations were higher in samples from the control group for the first hour; however, after two hours the levels were the same in all samples. Plasma MEGX levels increased continuously in both groups and were significantly higher in the control group samples. The sum of lidocaine + MEGX was higher in the control group for the first two hours but there was no significant difference between groups after three hours. CONCLUSIONS: Reduction of the potential for systemic toxicity by the addition of epinephrine to lidocaine is limited, because the reduction of the sum of the plasma concentrations of lidocaine and its active metabolite MEGX is small and limited to the initial phase of infusion.     

Epinephrine does not prolong lidocaine spinal anesthesia in term parturients

The effect of adding epinephrine to spinal anesthesia performed with lidocaine in young, healthy patients was determined in a prospective, controlled, randomized double-blind study. Patients were randomly assigned to one of two groups. One group received lidocaine in dextrose, and the other, lidocaine in dextrose plus epinephrine. Maximum segmental level, time to maximum level, and duration as determined by time to two-segment regression were determined for each of the two groups. There were no significant differences between the two groups in any of the observed parameters, most notably, duration. The present results substantiate those from a previous study in an older population that showed that epinephrine did not significantly prolong lidocaine spinal anesthesia. The present results do not, however, support the hypothesis based upon these earlier data that failure of epinephrine to prolong lidocaine spinal anesthesia is restricted to elderly patients.     

肾上腺素对利多卡因硬膜外麻醉时血流动力学的影响

目的 观察肾上腺素对利多卡因硬膜外麻醉时血流动力学的影响.方法 择期行骨科下肢手术患者40例,ASA Ⅰ或Ⅱ级,随机均分为肾上腺素(E)组和生理盐水(S)组,分别采用2%利多卡因加5 μg/ml肾上腺素或等容生理盐水进行硬膜外麻醉.采用阻抗心动图记录注药前即刻(T0)、注药后5、10、15、20、25、30 min(T1～T6)的MAP、HR、心脏指数(CI)、外周血管阻力指数(SVRI)和加速指数(ACI).结果 与T0时比较,E组在T1～T6时MAP和SVRI降低、CI和ACI升高、HR增快(P<0.05),而S组血流动力学差异无统计学意义.结论 肾上腺素加入利多卡因用于硬膜外麻醉可引起MAP和SVRI下降、CI和ACI升高、HR增快等血流动力学改变.     

Pharmacokinetics and the lung uptake of lidocaine during epidural anesthesia

In order to investigate the pharmacokinetics of lidocaine especially the lung uptake during epidural anesthesia, we measured the lidocaine concentrations of arterial and central venous blood simultaneously using a homogeneous enzyme immunoassay. Then the lung extraction ratio was calculated as (1-arterial lidocaine concentration/central venous lidocaine concentration) X 100%. With only epidural anesthesia, the lung uptake of lidocaine was above 30% during the first 40 minutes, but was less after additional administration. After general anesthesia with thiamylal, enflurane, nitrous oxide and oxygen, the lung uptake was 30 approximately 40% following initial and additional administrations. There was a positive correlation between the lung extraction ratio and the central venous lidocaine concentration 5 minutes after the initial administration. Having used laryngotracheal lidocaine spray during endotracheal intubation, the lung extraction ratio could not be calculated since this resulted in direct lidocaine administration to the lungs. In conclusion, the lung plays an important role in keeping the arterial lidocaine concentration low.     

Free lidocaine concentrations during continuous epidural anesthesia in geriatric patients

BACKGROUND AND OBJECTIVES: To evaluate the effects of aging on lidocaine pharmacokinetics, the plasma concentrations of total and free lidocaine and its metabolites were measured during continuous thoracic epidural anesthesia in middle-aged (age 41 +/- 9 years, n = 7) and elderly (age 72 +/- 2 years, n = 7) male patients. METHODS: After establishment of general anesthesia, 7 mL 1.5% lidocaine with epinephrine 1:200,000 was injected into the epidural space and subsequently infused at a rate of 5 mL/h for 5 hours. Plasma concentrations of total and free lidocaine, monoethylglycinexylidide (MEGX), and glycinexylidide (GX) were measured at 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, and 300 minutes after initial lidocaine injection using high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. RESULTS: The elderly group showed a stronger upward trend in the corrected free lidocaine concentrations and lower corrected total MEGX concentrations than the middle-aged group. CONCLUSIONS: Lidocaine metabolite activity in the elderly male patients was lower than that in the middle-aged male patients. Free lidocaine concentration is prone to increase in elderly patients. Caution must be exercised during continuous thoracic epidural anesthesia combined with general anesthesia in geriatric patients.     

Opioids inhibit febrile responses in humans, whereas epidural analgesia does not: an explanation for hyperthermia during epidural analgesia

BACKGROUND: Epidural analgesia is frequently associated with hyperthermia during labor and in the postoperative period. The conventional assumption is that hyperthermia is caused by the technique, although no convincing mechanism has been proposed. However, pain in the "control" patients is inevitably treated with opioids, which themselves attenuate fever. Fever associated with infection or tissue injury may then be suppressed by opioids in the "control" patients while being expressed normally in patients given epidural analgesia. The authors therefore tested the hypothesis that fever in humans is manifested normally during epidural analgesia, but is suppressed by low-dose intravenous opioid. METHODS: The authors studied eight volunteers, each on four study days. Fever was induced each day by 150 IU/g intravenous interleukin 2. Volunteers were randomly assigned to: (1) a control day when no opioid or epidural analgesia was given; (2) epidural analgesia using ropivacaine alone; (3) epidural analgesia using ropivacaine in combination with 2 microg/ml fentanyl; or (4) intravenous fentanyl at a target plasma concentration of 2.5 ng/ml. RESULTS: Fentanyl halved the febrile response to pyrogen, decreasing integrated core temperature from 7.0 +/- 3.2 degrees C. h on the control day, to 3.8 +/- 3.0 degrees C. h on the intravenous fentanyl day. In contrast, epidural ropivacaine and epidural ropivacaine-fentanyl did not inhibit fever. The fraction of core-temperature measurements that exceeded 38 degrees C was halved by intravenous fentanyl, and the fraction exceeding 38.5 degrees C was reduced more than fivefold. CONCLUSIONS: These data support the authors' proposed mechanism for hyperthermia during epidural analgesia. Fever during epidural analgesia should thus not be considered a complication of the anesthetic technique per se.     

Epidural morphine delays the onset of tourniquet pain during epidural lidocaine anesthesia

We conducted a randomized, double-blinded study to examine the onset time of tourniquet pain during epidural lidocaine anesthesia either with or without morphine in the epidural solution. Forty-five patients undergoing knee surgery with a thigh tourniquet were randomly allocated into 3 groups of 15 patients each: epidural morphine (EM; epidural administration of 17 mL of 2% lidocaine plus 2 mg of morphine, followed by IV injection of 0.2 mL of normal saline), IV morphine (IVM; 17 mL of 2% lidocaine plus 0.2 mL of normal saline, followed by IVM 2 mg IV), and control (17 mL of 2% lidocaine plus 0.2 mL of normal saline, followed by 0.2 mL of normal saline IV). The onset time of tourniquet pain was recorded. The level of sensory block was determined by the pinprick method at the occurrence of tourniquet pain. Hemodynamic changes and side effects of EM were also recorded. The onset time of tourniquet pain from both the epidural injection and the tourniquet inflation were significantly longer in the EM group (103 +/- 15 min and 80 +/- 15 min, respectively) compared with the IVM group (74 +/- 12 min and 50 +/- 12 min, respectively; P < 0.05) and the Control group (67 +/- 9 min and 45 +/- 9 min, respectively; P < 0.05). The level of sensory block at the onset of tourniquet pain and hemodynamic changes were not different among the three groups. Only two and three patients in the EM group complained of nausea/vomiting and pruritus, respectively. Respiratory depression was not observed in any patient. We conclude that epidural injection of the mixture of 2 mg of morphine and 2% lidocaine solution delayed the onset of tourniquet pain during epidural lidocaine anesthesia without significant morphine-related side effects. IMPLICATIONS: We examined the effect of epidural morphine on the onset of tourniquet pain during epidural lidocaine anesthesia. We found that the addition of 2 mg of morphine to epidural 2% lidocaine significantly delayed the onset of tourniquet pain without increasing morphine-related side effects.     

Epidural fentanyl speeds the onset of sensory block during epidural lidocaine anesthesia

BACKGROUND AND OBJECTIVES: Shortening the onset time of sensory block is a practical goal to improve the quality of epidural anesthesia. The addition of fentanyl to a local anesthetic solution is widely used during epidural anesthesia. This randomized double-blind study examined the onset time of sensory block during epidural lidocaine anesthesia with and without added fentanyl to the epidural solution. METHODS: Thirty-six young male patients undergoing knee arthroscopy were randomly allocated into 3 groups of 12 patients each: epidural fentanyl (EF, epidural administration of 17 mL of 2% lidocaine plus 100 microg fentanyl and followed by intravenous (IV) injection of 2 mL of normal saline); IV fentanyl (IF, epidural administration of 17 mL of 2% lidocaine plus 2 mL of normal saline and followed by IV injection of 100 microg of fentanyl); and control (C, epidural administration of 17 mL of 2% lidocaine plus 2 mL of normal saline and followed by IV injection of 2 mL of normal saline). The sensory block was assessed by pinprick method. The hemodynamic changes, postepidural shivering, and side effects of epidural fentanyl were also recorded. RESULTS: There was no difference in the distribution of age, weight, and height among the 3 groups. The onset time of sensory block up to T(10) dermatome was significantly more rapid in the EF group (8.3 +/- 3.7 minutes) than that of the IF group (13.1 +/- 4.2 minutes, P <.05) or C group (14.2 +/- 5.4 minutes, P <.05). The upper level of sensory block was also significantly higher in the EF group. Although the incidence of shivering was lower in the EF group, this did not reach statistical significance. Postepidural arterial blood pressures and heart rates were no different among the 3 groups. No nausea, vomiting, pruritus, respiratory depression, urinary retention, or hypotension were observed in any patients. CONCLUSION: Epidural injection of the mixture of 100 microg fentanyl and 2% lidocaine solution accelerated the onset of sensory block during epidural lidocaine anesthesia without increased side effects.     

Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia

Plasma concentration-time courses of lidocaine and its principal metabolites (monoethylglycinexylidide, MEGX, and glycinexylidide, GX) were studied during intermittent epidural injections of lidocaine HCl in eight female patients (ASA status 1). The initial dose (320-400 mg without epinephrine) followed by top-up injections of about 60% of the mean initial dose every 35-55 min resulted in a plasma accumulation of lidocaine: the peak concentration increased from 2.30 +/- 0.46 (mean +/- SD) microgram/ml following the first injection and 3.34 +/- 0.76 microgram/ml after the second, to 4.11 +/- 0.72 microgram/ml following the third. The maximum concentrations of MEGX and GX were 0.66 +/- 0.22 and 0.28 +/- 0.08 microgram/ml, respectively. A pharmacokinetic model could successfully fit the entire plasma concentration-time profile of lidocaine during repeated epidural injections (r2 = 0.886 to 0.983). Such pharmacokinetic variables as elimination half-life (t1/2, 2.33 +/- 0.43 h), apparent volume of distribution divided by bioavailability (Vd/F, 2.51 +/- 0.61 l/kg), and clearance divided by bioavailability (Cl/F, 11.65 +/- 1.21 ml X kg-1 X min-1) obtained from the female patients were in reasonable agreement with those reported from healthy females receiving the intravenous lidocaine HCl. A computer-aided simulation generated from using the mean kinetic data in a 50-kg woman predicted that plasma lidocaine concentration would reach the postulated toxic range (approximately equal to 6 microgram/ml) after the fourth supplementary dose under a similar dosing scheme as performed in this study. In conclusion, an accumulation of lidocaine in plasma occurs during a usual intermittent epidural dosing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma lidocaine concentrations during epidural blockade with isoflurane or halothane anesthesia.

Because isoflurane maintains hepatic blood flow at higher flows than halothane, we proposed that the elimination of lidocaine would be different between these two volatile anesthetics. The plasma lidocaine concentrations were determined in 14 female patients undergoing epidural blockade plus isoflurane anesthesia and compared with those obtained during halothane anesthesia for lower abdominal surgery. General anesthesia was maintained with isoflurane (0.46% +/- 0.04% [mean +/- SE] inspired, n = 7) or halothane (0.48% +/- 0.05% inspired, n = 7) and 67% nitrous oxide in oxygen. All patients received 2% lidocaine solution, 10 mL as a bolus dose and continuous administration at a rate of 10 mL/h, through the epidural catheter. The plasma lidocaine concentrations over 180 min after the epidural injection in patients receiving isoflurane were similar to those in patients receiving halothane. The results suggest that low inspired concentrations of isoflurane do not reduce plasma lidocaine concentrations in patients during epidural blockade, compared with halothane.     

Effects of epidural clonidine added to lidocaine solution upon the requirements of sedatives during epidural anesthesia

The authors studied 34 patients undergoing abdominal total hysterectomy in order to evaluate whether epidural clonidine added to lidocaine solution could alter the requirements of sedatives during epidural anesthesia. Patients were randomly assigned to one of four groups; 18 ml of 2% lidocaine with 1:200,000 clonidine (n = 6), 1:100,000 clonidine (n = 7), 1:200,000 epinephrine (n = 13), or neither (plain, n = 8). The requirements of sedatives (diazepam, thiamylal) and analgesic (butorphanol) prior to the second epidural injection were compared among the four groups. The dose of intravenous diazepam or thiamylal required for sedation in the patients receiving lidocaine with 1:100,000 clonidine had a tendency to be smaller as compared with those in other three groups. There was a significant difference (P less than 0.05) in the requirement of diazepam between the patients given lidocaine with 1:100,000 clonidine and those given plain lidocaine. The present results suggest that the addition of clonidine to lidocaine solution could reduce the requirements of sedatives in epidural anesthesia.     

Reversal of lidocaine with epinephrine epidural anesthesia using epidural saline washout

BACKGROUND AND OBJECTIVES: Prolonged motor and sensory block following epidural anesthesia can be associated with extended postoperative care unit stays and patient dissatisfaction. Previous studies have demonstrated a more rapid motor recovery following the administration of epidural crystalloids in patients who had received plain bupivacaine and lidocaine epidural anesthesia. However, epinephrine is commonly added to local anesthetics to improve the quality and prolong the duration of the epidural block. The objective of this study was to determine the relationship of 0.9% NaCl epidural catheter flush volume (i.e., washout) to the recovery of motor and sensory block in patients undergoing 2% lidocaine with epinephrine epidural anesthesia. METHODS: A prospective, randomized, double-blind study design was utilized. Thirty-three subjects scheduled for elective gynecologic or obstetrical surgical procedures underwent epidural anesthesia using 2% lidocaine with epinephrine (1:200,000). A T4 dermatome level of analgesia, determined by toothpick prick, was maintained intraoperatively. Following surgery, subjects were randomized to 1 of 3 treatment groups. Group 1 (control, n = 11) received no epidural 0.9% NaCl (normal saline [NS]) postoperatively. Group 2 (15 mL NS x 1, n = 10) received an epidural bolus of 15 mL NS. Group 3 (15 mL NS x 2, n = 12) received an epidural bolus of 15 mL NS postoperatively and a second 15-mL NS bolus 15 minutes later. Assessment of motor and sensory block was performed at 15-minute intervals until complete motor and sensory recovery. RESULTS: Times to partial and full motor and sensory recovery were significantly faster in the epidural NS groups than in the control group. Full motor recovery was more rapid in subjects receiving two 15-mL NS epidural NS boluses (30 mL total) compared with those receiving a single 15-mL NS bolus (108 +/- 9 min v 136 +/- 13 min) and significantly faster than control group subjects (153 +/- 14 min). Both NS x 1 and NS x 2 epidural bolus groups experienced significantly reduced times to complete sensory recovery when compared with the control group (NS x 1 = 154 +/- 13 min, NS x 2 = 153 +/- 9 min, control 195 +/- 14 min). CONCLUSIONS: A more rapid recovery of motor and sensory block in patients undergoing 2% lidocaine with epinephrine epidural anesthesia can be achieved with the use of 30 mL NS epidural washout. Reg Anesth Pain Med 2001;26:246-251.     

利多卡因椎管内麻醉的安全性问题

椎管内麻醉使用利多卡因的安全性问题影响着其临床应用,现就近年来利多卡因应用于椎管内麻醉产生神经系统后遗症的临床及实验研究作了综述,并提出了其应用于椎管内麻醉的临床安全剂量作为参考。     

Comparison of pH-adjusted lidocaine solutions for epidural anesthesia

One hundred forty-eight adult patients having epidural anesthesia for cesarean section, postpartum tubal ligation, lower extremity orthopedic procedures, or lithotriptic therapy were assigned to five groups. Group 1 patients were given a commercially prepared 1.5% lidocaine solution with 1:200,000 epinephrine plus 1 ml of normal saline per 10 ml of lidocaine; the solution pH was 4.6. Group 2 patients were given commercially prepared 1.5% lidocaine solution plus 1:200,000 epinephrine, with 1 mEq (1 ml) NaHCO3 per 10 ml of lidocaine; the solution pH was 7.15. Group 3 patients received the commercial solution of 1.5% lidocaine with 1:200,000 epinephrine; the solution pH was 4.55. Group 4 patients were given a mixture of 18 ml of 2% lidocaine with 30 ml of 1.5% lidocaine, both commercially packaged with 1:200,000 epinephrine, plus 1 mEq (1 ml) of NaHCO3 added per 10 ml of solution; the solution pH was 7.2. Group 5 patients received 1.5% plain lidocaine to which epinephrine was added to a final concentration of 1:200,000; the solution pH was 6.35. Times of onset of analgesia (time between the completion of the anesthetic injection and loss of scratch sensation at the right hip (L-2 dermatome] and of surgical anesthesia (time between completion of injection and loss of discomfort following tetanic stimulation produced by a nerve stimulator applied to skin on the right hip) were significantly more rapid in the groups that received the pH-adjusted solutions (groups 4 and 2). Group 4 had the fastest mean onset time, 1.92 +/- 0.17 min, followed by group 2, 3.31 +/- 0.23 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Thoracic epidural anesthesia does not influence the occurrence of postoperative sustained atrial fibrillation

BACKGROUND: To evaluate whether thoracic epidural anesthesia (TEA) can reduce the incidence of atrial fibrillation (AF) after coronary artery bypass grafting (CABG). METHODS: Forty-one patients undergoing CABG were treated with TEA intraoperatively and postoperatively. Another 80 patients served as the control group. The sympathetic and parasympathetic activities were evaluated by analysis of neuropeptides, catecholamines and heart rate variability (HRV), preoperatively and postoperatively. RESULTS: Postoperative AF occurred in 31.7% of the TEA-treated patients and in 36.3% of the untreated patients (p = 0.77). TEA significantly suppressed sympathetic activity, as indicated by a less pronounced increase of norepinephrine and epinephrine (p = 0.03, p = 0.02) and a significant decrease of neuropeptide Y (p = 0.01) postoperatively in TEA-treated patients compared to untreated patients. The HRV variable expressing sympathetic activity was significantly lower and the postoperative increase in heart rate was significantly less in the TEA group than in the control group after surgery (p = 0.01, p < 0.001). Among patients developing AF, the maximal number of supraventricular premature beats per minute increased significantly in untreated patients postoperatively but remained unchanged in TEA-treated patients (p = 0.004 versus p = 0.86). CONCLUSIONS: TEA has no effect on the incidence of postoperative sustained AF, despite a significant reduction in sympathetic activity.