Epidural infusion of low dose bupivacaine after combined spinal-epidural anesthesia using needle through needle method provided no analgesic effect on postoperative pain after caesarian section

BACKGROUND: In order to evaluate the analgesic efficacy of low dose epidural bupivacaine infusion with and without morphine after caesarean section we performed combined spinal-epidural anesthesia (CSEA) using needle through needle method. Three different epidural analgesic regimens were compared retrospectively. METHODS: The number of analgesic use during 24 hours after operation was compared. Patients were categorized into three groups; group N : intraoperative bolus epidural morphine (2.5 mg) alone, group L : bolus morphine (2.5 mg) plus epidural bupivacaine infusion (32 ml of 0.2% bupivacaine) at a rate of 2.1 ml x hr(-1), group M : bolus morphine (2.4 mg) plus epidural bupivacaine-morphine (33 ml of 0.2% bupivacaine containing morphine 2.3 mg) infusion at a rate of 2.1 ml x hr(-1). Used analgesics included pentazocine 15 mg i.m., diclofenac 25 mg suppo. and loxoprofen 60 mg p.o.. RESULTS: The mean number of analgesic use during the first 24 hours in group M (0.29 +/- 0.46) was significantly smaller than those of group N (0.97 +/- 0.91) and group L (0.84 +/- 0.95). Percentage of patients requiring no analgesic during the first 24 hours was significantly less in group M (70.8%) than in group N (33.4%) and group L (42.1%). CONCLUSIONS: A 2.1 ml x hr(-1) infusion of epidural bupivacaine has no analgesic effect after caesarean section under CSEA using NTN method.     

Bupivacaine pharmacokinetics during epidural anaesthesia in children

Blood concentrations and pharmacokinetic parameters of bupivacaine were measured after epidural injection in children aged from 1 to 7 years. The children were allocated to two groups. In Group 1 (five children), pharmacokinetic parameters were measured after a single bolus injection of bupivacaine 0.25% with adrenaline 1:200,000. In Group 2 (eight children), pharmacokinetic parameters were measured after the initial injection and the second injection. The same local anaesthetic was used. The volume of the second injection was half of the initial volume. In children of Group 1, maximum mean concentration (CPmax) was 0.64 +/- 0.05 microgram ml-1, time to maximum concentration (Tmax) 19.2 +/- 3.9 min, vascular absorption (T1/2 abs) 4.3 +/- 1.5 min, terminal half-life (T1/2 beta) 227 +/- 37.7 min, volume of distribution (Vd) 3.4 +/- 0.51 kg-1, and total body clearance (Clt) 11.0 +/- 2.0 ml min-1 kg-1. When compared to an adult's pharmacokinetic parameters, both Vd and Clt were increased, so that T1/2 beta remained essentially unchanged. In children of Group 2, the first repeat injection was performed at 110 +/- 6.9 min. Mean CPmax increased significantly (20% after the second injection), whereas the values of the pharmacokinetic parameters measured did not differ significantly from those measured in children in Group 1. The results obtained in the present study demonstrate that the pharmacokinetic parameters of bupivacaine in children do not differ markedly from those reported in adults and that in the recommended dosage, the mean maximum concentrations, even after the second injection, are less than the presumed toxic levels.     

Bupivacaine disposition in mother, fetus, and neonate after spinal anesthesia for cesarean section

Uptake of bupivacaine from the subarachnoid space and its placental transfer were measured in six patients undergoing elective cesarean section. Maternal plasma levels (59 +/- 32 ng/ml) were only about 5% of those found in a comparable previous study of epidural anesthesia. Mean plasma umbilical venous bupivacaine levels (20.2 +/- 21 ng/ml) were 7% of those found after epidural anesthesia. Mean umbilical venous/maternal venous bupivacaine ratios were 0.34 +/- 0.12 and mean umbilical arterial/umbilical venous ratios were 0.81 +/- 0.30. No bupivacaine was detectable in neonatal plasma 24 hr after delivery. Neonatal urine had measurable levels of both bupivacaine and its inactive metabolite, 2,6-pipecolylxylidine (PPX), for at least 36 hr after delivery. The results demonstrate that bupivacaine crosses the placenta and reaches the fetus, but in very low amounts. This transplacental passage occurs despite injection of only small doses of a very highly protein bound drug into the subarachnoid space.     

Blood flow in the operating field during controlled hypotension by nitroglycerin, trimetaphan and prostaglandin E1

We used the laser flowmeter to measure and compare the effect of nitroglycerin (TNG), trimetaphan (TMP) and prostaglandin E1 (PGE1) on the blood flow of operating field during hypotension induced by each drug. The study was done in 33 patients (TNG:13, TMP:13 and PGE1:7) anesthetized with modified NLA who underwent radical mastectomy. We put the probe of the laser flowmeter on the skin of the opposite breast to the operating field and measured the skin blood flow change. Measurements were made before and during hypotension induced by each drug. TMP-induced hypotension decreased blood flow significantly (P less than 0.05), but TNG and PGE1 had no significant effect. Intraoperative blood losses of TNG and PGE1 group were not significantly larger than that of TMP group. From this study we conclude that TNG, TMP and PGE1 can dry the operating field and decrease intraoperative blood loss similarly. Therefore we should choose the drugs to induce hypotension considering the effect of the drug on blood flow of the important organs and each patient's complications.     

Comparative pharmacokinetics of bupivacaine and ropivacaine, a new amide local anesthetic

The pharmacokinetics of ropivacaine, a new amide local anesthetic, and bupivacaine were determined in dogs after IV and epidural administration. After 15-minute IV infusions of 3.0 mg/kg ropivacaine (n = 6) and 3.4 mg/kg bupivacaine (n = 4), the maximum arterial concentrations (Cmax) of ropivacaine averaged 2.41 +/- 0.52 micrograms/ml compared with 3.35 +/- 0.16 micrograms/ml of bupivacaine. The elimination half life (t 1/2 beta) of ropivacaine (25.9 +/- 1.7 min) was significantly shorter than for bupivacaine (39.1 +/- 13.3 min) after IV infusion. This was reflected by mean clearance values (Cl) for ropivacaine of 41.1 +/- 8.2 ml.min-1.kg-1 compared with 32.3 +/- 4.8 ml.min-1.kg-1 for bupivacaine, although the difference was not statistically significant. After epidural injections (ropivacaine n = 6; bupivacaine n = 5), a dose-related increase in Cmax was observed with both drugs. Although Cmax tended to be higher for ropivacaine, a significant difference was only attained when comparing Cmax after administration of 0.25% plain solutions of both agents. The addition of epinephrine did not consistently decrease the Cmax of either agent. The apparent t 1/2 beta of both agents was significantly longer after epidural administration than after IV infusion. No differences existed between t 1/2 beta values for ropivacaine and bupivacaine after epidural administration. Total body clearance of both agents tended to be lower after epidural administration, particularly when epinephrine-containing solutions were employed. Little difference existed between the two drugs when equivalent solutions were administered.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

The effect of hydroxyethylstarch infusion on bupivacaine pharmacokinetics in rats

BACKGROUND: Bupivacaine is the agent most often used for labor analgesia. However, the risk of accidental intravascular injection of this drug and consequent acute systemic toxicity is ever-present. Although hydroxyethylstarch (HES) is preferred over crystalloid for prevention of hypotension during regional anesthesia, the pharmacokinetics of bupivacaine during fluid preloading has not been studied. METHODS: Twenty-four awake Sprague-Dawley rats were randomly allocated to receive the continuous intravenous infusion of HES 70K, 200K or 400K, or normal saline (NS). After 1 hour of prehydration all animals received bupivacaine, 1mg kg(-1), bolus, followed by a continuous infusion, 0.4mg kg(-1) min(-1) for 15 minutes. After the completion of bupivacaine infusion serial arterial blood samples to determine the plasma bupivacaine concentration were obtained. The plasma concentration-time profile of bupivacaine was fitted to a two-compartment open model, and the estimated intercepts and slopes were used for calculation of standard pharmacokinetic parameters. RESULTS: The mean peak bupivacaine concentration during HES 400K infusion was significantly lower than during NS infusion (1488 +/- 302 ng ml(-1) vs 2388 +/- 582 ng ml(-1)). Mean volume of distribution in each of the three HES groups was greater than in NS group. Mean area under curves (AUC) during HES 200K and HES 400K infusions were significantly lower than during NS infusion (32534 +/- 4180 and 29619 +/- 4431 min ng ml(-1), respectively, vs 39802 +/- 6268 min ng ml(-1)). Mean total clearance of bupivacaine during HES 200K and HES 400K infusions was significantly higher than during NS infusion (115 +/- 14 and 132 +/- 15 ml min(-1) kg(-1), respectively, vs 92 +/- 14 ml min(-1) kg(-1)). CONCLUSION: Our results suggest that the increased volume of distribution during HES infusion could be counterbalanced by the increased total clearance, resulting in unchanged half-life or elimination rate constant of bupivacaine.     

Bupivacaine for intercostal nerve blocks in children: blood concentrations and pharmacokinetics

A pharmacokinetic evaluation of bupivacaine was carried out after intercostal nerve blocks performed on 28 occasions in 27 children varying in age from 3 months to 16 yr. Bupivacaine HCl, 0.5%, with epinephrine 1:200,000 was employed. Doses of 2 mg/kg, 3 mg/kg, and 4 mg/kg resulted in peak whole blood arterial bupivacaine (base) concentrations (mean +/- SD) of 0.77 +/- 0.25 microgram/ml, 1.37 +/- 0.23 microgram/ml, and 1.87 +/- 0.53 microgram/ml, respectively. Calculated pharmacokinetic parameters (mean +/- SD) were the following: apparent volume of distribution (VD beta), 2.8 +/- 0.8 L/kg; steady-state volume of distribution (VDss), 2.7 +/- 0.7 L/kg; elimination half-life (t1/2 beta), 147 +/- 80 min; and total body clearance (Cl), 16.0 +/- 7.4 ml X min-1 X kg-1, or 382 +/- 201 ml X min-1 X m-2. Compared with data reported for adult patients, our data indicate that the volume of distribution is greater and clearance is more rapid in children than in adults. The absorption of local anesthetic from the intercostal space appears to be more rapid in children than adults. In an additional group of 11 children, the relationship of the bupivacaine blood:plasma concentration ratio (lambda) to hematocrit was investigated. Hematocrit in this group ranged from 30 to 59, and lambda varied from 0.47 to 0.82. There was a significant relationship between lambda and hematocrit defined by the equation lambda = -0.0079 Hct + 1.028 (r = 0.72, P less than 0.05). Reporting bupivacaine concentration in terms of plasma concentration may introduce an artifact that is dependent on the hematocrit, and we therefore suggest that whole blood concentration values be reported by investigators in the future.     

Combined spinal and epidural anesthesia for cesarean section: a retrospective study with 0.5% hyperbaric bupivacaine

BACKGROUND: We investigated retrospectively the relationship between the intrathecal dose of 0.5% hyperbaric bupivacaine and the use of 2% mepivacaine through an epidural catheter. METHODS: Forty-nine patients undergoing cesarean section with combined spinal and epidural anesthesia (CSEA) were analyzed. They were divided into two groups; with (CSEA group) and without additional epidural injection group (spinal group). RESULTS: In the CSEA group (24 patients received 1.2 +/- 0.4 ml of 0.5% hyperbaric bupivacaine), 5-10 ml of 2% mepivacaine were required to achieve the adequate surgical anesthesia. In the spinal group (25 patients received 1.6 +/- 0.3 ml of 0.5% hyperbaric bupivacaine), cesarean section was performed without additional mepivacaine before delivery. The analgesic level and the amount of fluid infusion were similar in the two groups. However, 20% of patients in the spinal group showed hypotension (systolic blood pressure below 80 mmHg), although no patients in the CSEA group developed hypotension. The amount of ephedrine used before delivery was significantly larger in the spinal group (8.9 +/- 7.7 mg) than in the CSEA group (3.9 +/- 4.3 mg). CONCLUSIONS: Spinal anesthesia induced by 1.2 ml of 0.5% hyperbaric bupivacaine with sequential epidural block induced by 5-10 ml of 2% mepivacaine caused no hypotension during cesarean section.     

Systemic absorption of 2% lidocaine from the lumbar epidural space

The curves of lidocaine (LDC) plasma levels versus time were evaluated in a group of 16 patients receiving single epidural injections of 2% LDC for each metamer to be anesthesized. LDC absorption from epidural space is fairly rapid (tmax = 17 +/- 4 min and t1/2a = 6.2 +/- 1.7 min). This results in very shape peak plasma levels (2.97 +/- 0.87 micrograms/ml with 2% LDC). The remaining pharmacokinetic parameters were: Ke = 0.0057 +/- 0.0022 min-1 and Vd = 1.5 +/- 0.5 l/kg. In all patients adequate levels for operation were obtained.     

Epidural blood flow and regression of sensory analgesia during continuous postoperative epidural infusion of bupivacaine

Epidural blood flow was measured in seven patients undergoing elective abdominal surgery during combined lumbar epidural and general anesthesia. After an initial dose of 20 ml plain bupivacaine 0.5%, a continuous epidural infusion of bupivacaine 0.5% (8 ml/hr) was given for 16 hours for postoperative pain relief. The epidural blood flow was measured by a local 133Xe clearance technique in which 15-35 MBq 133Xe diluted in 1 ml saline was injected through the epidural catheter on the day before surgery (no bupivacaine), 30 minutes after the initial dose of bupivacaine on the morning before surgery, and 8, 12, and 16 hours later during the continuous infusion. Initial blood flow was 6.0 +/- 0.7 ml/min per 100 g tissue (mean +/- SEM). After epidural bupivacaine, blood flow increased in all seven patients to 7.4 +/- 0.7 ml (P less than 0.02). Initial level of sensory analgesia was T4.5 +/- 0.17 (mean +/- SEM). Postoperatively, two patients maintained the initial level of sensory analgesia and low pain score throughout the 16-hour study. In these two patients epidural blood flow remained constant after the initial increase. Flow increased further to 10.3 +/- 0.8 ml/min per 100 g tissue (P less than 0.03) in the other five patients as the level of sensory analgesia regressed postoperatively. These data suggest that changes in epidural blood flow during continuous epidural infusion of bupivacaine, and thus changes in rates of vascular absorption of bupivacaine from the epidural space, may be an important factor contributing to differences in rates of regression of sensory analgesia.     

Lack of influence of cimetidine on bupivacaine levels during parturition

The concurrent use of cimetidine as a prophylactic antacid and bupivacaine as a local anesthetic for epidural anesthesia for cesarean section has been promoted. However, cimetidine is known to inhibit clearance of many drugs by reducing hepatic blood flow and by inhibiting cytochrome P-450 enzymes. The purpose of this study was to determine whether cimetidine during epidural anesthesia alters the metabolism, disposition, protein binding, or placental transfer of bupivacaine. Thirty-six patients undergoing cesarean section with 0.5% bupivacaine for epidural anesthesia were studied. Sixteen patients received cimetidine (300 mg IM) 1-4 hr before cesarean section and 20 control patients received sodium citrate (30 ml PO) 10 min preoperatively. Bupivacaine and its inactive metabolite, 2,6-pipecolylxylidine (PPX) were quantitated by gas chromatography/mass spectrometry. Maternal plasma concentration time curves, fetal/maternal ratios at delivery, cord vein/cord artery ratios. PPX/bupivacaine ratios, and maternal and neonatal urinary excretion were compared between the two groups. No significant differences could be found between the groups in any of the outcome variables. However, in the presence of cimetidine, the percentage of unbound bupivacaine significantly increased from 1.36 +/- 0.63 to 1.66 +/- 0.78%. The results suggest that a single 300-mg IM dose of cimetidine does not significantly affect bupivacaine disposition or metabolism in parturients when given 1-4 hr before anesthesia.     

Epinephrine enhances analgesia produced by epidural bupivacaine during labor

Reports on the analgesic and hemodynamic effects of epinephrine added to bupivacaine for epidural use in obstetrics are conflicting. In this study, healthy parturients received in a random manner either 10 ml of 0.25% bupivacaine (n = 50) or 10 ml of 0.25% bupivacaine with 1:300,000 epinephrine (n = 50) epidurally. Epinephrine enhanced the analgesia produced by bupivacaine: onset was hastened (5.8 +/- 0.6 vs 8.7 +/- 0.8 min, mean +/- SEM, P less than 0.05), duration prolonged (123 +/- 7.0 vs 92 +/- 5.0 min, P less than 0.05), and the number of women requiring additional local anesthetic for analgesia decreased (9 vs 18, P less than 0.05) compared to the group receiving plain bupivacaine. The incidence of hypotension did not differ between groups. Maternal heart rate increased only after injection of the epinephrine-containing solution. The authors conclude that epinephrine 1:300,000 modestly but statistically significantly improves the analgesic efficacy of epidurally administered 0.25% bupivacaine during labor.     

Epidural morphine improves pain relief and maintains sensory analgesia during continuous epidural bupivacaine after abdominal surgery

Twenty patients scheduled for elective major abdominal surgery were matched into two groups with regard to age, sex, height, body weight, and surgical procedure. Both groups received general anesthesia plus lumbar epidural analgesia with similar loading doses of bupivacaine 0.5% (23.1 +/- 1.0 and 23.3 +/- 0.8 ml) (mean +/- SEM) followed by continuous infusion of plain bupivacaine 0.5% (8 ml/hr) plus, in one group, epidural morphine (0.5 mg/hr). Pain score on a 5-point scale and sensory analgesia (pin prick) were assessed hourly for 16 hours after skin incision. If sensory analgesia decreased more than 5 segments from preoperative levels or if pain scores reached 2 (moderate pain), the patients were removed from the study, and pain was treated with other methods. Preoperative mean (+/- SEM) sensory levels of analgesia were similar in the bupivacaine and the bupivacaine-morphine groups (T3.4 +/- 0.5 and T3.3 +/- 0.4, respectively). In the group receiving only bupivacaine, sensory analgesia regressed over time with a simultaneous increase in pain score. Thus, within 10 hr after skin incision, seven patients in this group were discharged from the study, and 16 hr after incision only one patient maintained initial level of sensory analgesia. In contrast, each patient receiving bupivacaine plus morphine had stable sensory analgesia and was completely free of pain as indicated by a mean pain score of zero during the 16-hr observation period. Thus epidural morphine may improve pain relief and maintain analgesia during continuous epidural bupivacaine administration after abdominal surgery.     

Pharmacokinetics of Bupivacaine after Continuous Epidural Infusion in Infants with and without Biliary Atresia

Background: Continuous epidural infusion of bupivacaine is widely practiced for postoperative pain relief in pediatric patients. However, bupivacaine may induce adverse effects in infants (convulsions or cardiac arrhythmias), likely because of decreased hepatic clearance and serum protein binding capacity. The authors wanted to examine the complex relations between age, [alpha]-1 acid glycoprotein (AAG) concentration, and unbound and total bupivacaine serum concentrations in infants receiving bupivacaine epidurally for 2 days.

Methods: Twenty-two infants aged 1-7 months (12 with biliary atresia and 10 with another disease) received a continuous epidural infusion of 0.375 mg [middle dot] kg-1 [middle dot] h-1 bupivacaine during 2 days (during and after surgery). Unbound and total bupivacaine concentration in serum was measured 0.5, 4, 24, and 48 h after infusion initiation. AAG concentration was measured in serum before and 2 days after surgery. In eight additional infants, the blood/plasma concentration ratio was measured in vitro at whole blood concentrations of 2 and 20 [mu]g/ml. Bupivacaine concentration was fitted to a one-compartment model to calculate basic pharmacokinetic parameters.

Results: No adverse effects were observed. AAG increased markedly after surgery, and the increase was correlated to both age and preoperative AAG concentration. Two infants aged 1.8 months had unbound concentrations greater than 0.2 [mu]g/ml. Clearance of unbound drug significantly increased with age. Because of increased drug binding, clearance of bound drug decreased both with time (from 0.5 to 48 h) and with age. Blood/plasma ratio was 0.77 +/- 0.08 and 0.85 +/- 0.24 at 2 and 20 [mu]g/ml, respectively.     

Continuous epidural infusion of morphine for treatment of pain after thoracic surgery: a new technique

We evaluated postoperative pain relief and the incidence of side effects of three methods of thoracic epidural analgesia. Ninety patients, divided into three equal groups, received postoperative analgesia after thoracic surgery either as intermittent epidural injections of bupivacaine (25 mg/5 ml, 0.5% solution) as needed, or, intermittent epidural injections of morphine (5 mg/5 ml of normal saline, 0.1% solution) as needed, or continuous epidural infusion of morphine (0.1 mg, in 1 ml of normal saline) per hour supplemented with intravenous morphine (2 mg) upon request. Pain relief was evaluated by each patient on a pain scale visual analogue and by pain relief questionnaire for a period of 72 hr. Postoperative pain relief was achieved equally with these three methods of epidural analgesia in all patients with no significant difference between groups. Intermittent epidural injection of bupivacaine relieved pain for 4.9 +/- 1.9 (SD) hr/injection and was associated with urinary retention in all patients, with numbness and weakness of the hands in 12 patients, and with severe hypotension in 7 patients. Intermittent epidural injection of morphine relieved pain for 5.8 +/- 2.3 hr/injection and was associated with urinary retention in all patients, with pruritus in 12 patients, and with central narcosis and respiratory depression in 8 patients. Continuous epidural infusion of morphine with occasional intravenous morphine (2 mg) supplementation also effectively relieved postoperative pain and was associated with minimal systemic side effects. One patient complained of pruritus, and two patients developed urinary retention.(ABSTRACT TRUNCATED AT 250 WORDS)     

RETRACTED ARTICLE: Hemodynamics, intra-mucosal pH and regulators of circulation during perioperative epidural analgesia

PURPOSE: To evaluate the effects of perioperative epidural analgesia on hemodynamics, splanchnic perfusion and regulators of circulation. METHODS: Twenty patients undergoing aortic surgery were randomised into two groups: epidural analgesia group (EAG): epidural analgesia with bupivacaine (15 ml, 0.125%) was started before surgery. Eight and 16 hr postoperatively 10 ml bupivacaine 0.125% and 1 mg morphine were given. Control group (COG): patients received no epidural catheter. Monitoring included pulmonary artery catheter and gastric tonometer. Norepinephrine, epinephrine, renin, ADH, ANP and endothelin were measured: before epidural analgesia (T0), before aortic clamping (T1), 20 min after aortic clamping (T2), after declamping the first leg (T3), at end of surgery (T4), one hour (T5) and 24 hr postoperatively (T6). RESULTS: At T5 mean arterial blood pressure decreased in EAG compared with baseline (86 +/- 16 to 75 +/- 8 mmHg) and compared with COG (75 +/- 8 vs 84 +/- 11 mmHg). At T2 pulmonary capillary wedge pressure and cardiac index increased and at T6 decreased in both groups. Systemic vascular resistance decreased at T I and at T3-T5 in EAG compared with COG and at T1 and T3-T6 to baseline (1472 +/- 448 to 1027 +/- 184 dyn x sec x cm(-5) x m(-2)). In EAG and in COG, pHi decreased compared with baseline but without group differences. In both groups, epinephrine, norepinephrine, renin, and ADH levels increased from baseline. Endothelin and ANP levels showed no changes. CONCLUSIONS: Perioperatively administrated epidural bupivacaine has no beneficially effects on hemodynamics, pHi or release of regulators of circulation.     

Continuous block of the femoral nerve after surgery of the knee: pharmacokinetics of bupivacaine

Ten ASA Class 1 and 2 patients, aged from 16 to 56 years (mean +/- SD: 37 +/- 17 years), scheduled for knee surgery were studied. At the end of the surgical procedure under general anesthesia, an epidural catheter was inserted in the femoral space. After X-ray opacification, a bolus of 2.5 mg.kg-1 of 0.5% bupivacaine with epinephrine was injected. A maintenance infusion was performed during 48 hours with 0.25 mg.kg-1.h-1 of 0.125% bupivacaine without epinephrine. Pain score recorded with an visual analogue scale was 5.0 +/- 1.9 before femoral block. Pain score decreased significantly from 6 to 48 hours. Plasma bupivacaine levels at 24, 36 and 48 hours were significantly higher than the levels obtained at 30 min, 1, 6 and 12 hours. Mean plasma bupivacaine level at steady state was 1.78 +/- 0.59 micrograms.ml-1. Clearance of bupivacaine was 2.59 +/- 0.91 ml.min-1.kg-1. No neurologic complications have been recorded.     

Effect of epinephrine on epidural, intrathecal, and plasma pharmacokinetics of ropivacaine and bupivacaine in sheep

BACKGROUND: Local vasoconstriction induced by epinephrine added to epidural local anaesthetics has been shown to improve their quality and duration of action in several clinical reports. There are several assumptions on the mechanisms. This study was designed to evaluate the influence of epinephrine on transmeningeal uptake of epidurally administered ropivacaine and bupivacaine by measuring local anaesthetic concentrations in the epidural and intrathecal spaces and in plasma. METHODS: Ropivacaine (50 mg) and bupivacaine (30 mg) were administered epidurally in sheep with and without epinephrine (75 microg). A microdialysis technique was used to simultaneously measure epidural and intrathecal drug concentrations. Resulting dialysate and plasma concentrations were used to calculate pharmacokinetic parameters for ropivacaine and bupivacaine. RESULTS: Co-administration of epinephrine decreased epidural clearance for ropivacaine [0.6 (sd 0.1) vs 0.4 (0.1) ml min(-1)] but not significantly for bupivacaine [1.2 (0.4) vs 0.8 (0.3) ml min(-1)]. The resultant increase in epidural area under the concentration-time curves (31% for ropivacaine and 52% for bupivacaine) was also observed in the intrathecal space (21% increase for ropivacaine and 37% for bupivacaine). There was no significant influence of epinephrine on ropivacaine plasma pharmacokinetics. Plasma Cmax for bupivacaine was decreased. CONCLUSIONS: These results show that epinephrine decreases the clearance and distribution processes involved in epidural disposition of ropivacaine and bupivacaine, leading to an increased uptake into the intrathecal space with an apparent more pronounced effect for bupivacaine.     

Comparative pharmacokinetics of pipecuronium bromide, pancuronium bromide and vecuronium bromide in anesthetized man

The pharmacokinetics of pipecuronium bromide was studied in 9 male patients (ASA class 1-2, 20-65 years of age). Following a single intravenous dose of pipecuronium 0.08 mg.kg-1, plasma levels were measured by capillary gas chromatography. Plasma concentration-time curves were evaluated by fitting the data to a bi-exponential equation. The pharmacokinetic parameters of pipecuronium were compared with those of pancuronium (0.08 mg.kg-1) and vecuronium (0.08 mg.kg-1) previously obtained under the same anesthesia (66% N2O, 33% O2 and 1% halothane). With pipecuronium, following pharmacokinetic parameters were obtained; distribution half-life; T1/2 alpha = 3.9 +/- 0.7 min (mean +/- SEM), elimination half-life; T1/2 beta = 102 +/- 12 min, volume of the central compartment; V1 = 95 +/- 13 ml.kg-1, volume of distribution at steady state; Vdss = 264 +/- 41 ml.kg-1, clearance; Cl = 1.8 +/- 0.2 ml.min-1.kg-1. Microconstants of two-compartment open models (k12, k21, k10) were also calculated. Using Mann-Whitney's U-test, these parameters of pipecuronium were compared with those of pancuronium (n = 3) and vecuronium (n = 4). V1 and Vdss of pipecuronium were significantly larger than those of pancuronium (V1; 38 +/- 12 ml.kg-1 and Vdss; 120 +/- 4 ml.kg-1) (both P less than 0.10). Reflecting the larger central volume of pipecuronium, pipecuronium tended to have a larger clearance than that of pancuroniumu (Cl; 1.1 +/- 0.2 ml.min-1.kg-1).(ABSTRACT TRUNCATED AT 250 WORDS)