Administration Of Bupivacaine Research Articles

Intraperitoneal Bupivacaine Does Not Effectively Reduce Pain After Laparoscopic Cholecystectomy: A Randomized, Placebo-Controlled and Double-Blind Study

The analgesic effect of intraperitoneal infusion of local anesthesia after laparoscopic cholecystectomy is controversial, and the reported results range from considerable pain reduction to no significant pain reduction. In this randomized, placebo-controlled and double-blind study, we examined the efficacy of intraperitoneal administration of bupivacaine at the end of surgery in 65 patients undergoing elective laparoscopic cholecystectomy. Pain score was assessed using a visual analog scale 2 hours, 4 hours, 8 hours, 24 hours, and 48 hours after surgery. The peak expiratory flow was evaluated preoperatively and 2 hours, 4 hours, 8 hours, and 24 hours after surgery. The daily analgesic consumption was recorded. The authors only detected an analgesic effect in the heavier (body weight >77 kg) subgroup of patients at 2 hours, but detected no significant improvement of the peak expiratory flow, no decrease in the analgesic medication requirement, and no influence on the duration of hospital stay.

Comparison of 0.5% intrathecal bupivacaine with 0.5% intrathecal ropivacaine in the treatment of refractory cancer and noncancer pain conditions: Results from a prospective, crossover, double-blind, randomized study

Background and Objectives: Intrathecal (IT) administration of bupivacaine (BUP) for treatment of “refractory” pain has sometimes been associated with unacceptable side effects. This study was undertaken to determine if IT-ropivacaine (ROP) can reduce the rate and intensity of these side effects e.g., urinary retention, paresthesia, and particularly, paresis with gait impairment. A prospective, crossover, double-blind, randomized study. Methods: Twenty-one patients were enrolled, 9 dropped out of the study, and data were analyzed from 12 patients. Patients were treated by insertion of IT tunneled nylon catheters, continuous infusion of 0.5% ROP followed by 0.5% BUP or 0.5% BUP followed by 0.5% ROP solutions from an external electronic pump. Each local anesthetic was infused for 7 days, and their order of infusion randomized. The comparative efficacy of the ROP and BUP IT infusions was assessed from the daily doses of IT ROP and IT BUP, oral and parenteral opioids, and daily scores of nonopioid analgetic and sedative drug consumption. Self-reported pain intensity (visual analogue scale [VAS] mean scores) and scores of Bromage relaxation, ambulation, nocturnal sleep pattern, rates of side-effects attributable to the IT drugs, the patients' assessment of the IT ROP v the IT BUP periods of the trial, and the comparative daily cost of IT ROP v IT BUP were recorded. Results: The daily doses of the local anesthetics used were 23% higher for ROP than for BUP. Further, the daily cost was ≈3 times higher for ROP than for BUP. No other significant differences between IT ROP and IT BUP were found. Conclusion: The results of this study do not support the hypothesis that IT infusion of 0.5% ROP has advantages over IT infusion of 0.5% BUP when administered for relief of “refractory” pain. Reg Anesth Pain Med 2000;25:480-487.

Haemodynamic, endocrine and nociceptive response to gynaecological procedures under epidural local anaesthesia during continuous epidural infusion or bolus epidural fentanyl dosing

This study aimed to evaluate the analgesic effects and hormonal responses of a single epidural bolus compared to continuous epidural infusion of fentanyl as supplements to intraoperative local epidural anaesthesia for major gynaecological surgery. Forty patients undergoing total vaginal hysterectomy were randomised to receive in a double blind fashion either 1.5 μg kg−1 fentanyl epidurally (group A) or saline (group B) as bolus injections followed by epidural infusion of saline or fentanyl (0.7 μg kg−1h−1) respectively at a rate of 10 ml h−1. Postoperative pain intensity was assessed by visual analogue scale (VAS). Prolactin and cortisol plasma levels were used as stress markers. The onset of anaesthesia was significantly shorter in group A (p<0.05) but the duration of T10 blockade was significantly longer in group B (p<0.01). Pain intensity was significantly higher in group A at 90, 105 and 120 minutes after skin incision (p<0.001). There was no intraoperative difference in heart rate or mean arterial pressure between the two groups nor was there any difference in the incidence of adverse effects such as nausea, vomiting or shivering. Both groups had a progressive decrease in serum cortisol and prolactin concentrations 30 and 60 min after skin incision, but cortisol and prolactin concentrations were higher in group A (p<0.05) 120 minutes after skin incision. Our observations suggest that perioperative continuous epidural infusion of fentanyl begun intraoperatively attenuates the endocrine stress response, but a bolus dose of fentanyl given along with bupivacaine lacks this protective effect. A possible explanation for these findings is that an infusion begun intraoperatively, just after administration of epidural bupivacaine, prolongs the duration of sensory blockade and provides a better quality of analgesia, and thereby attenuates the endocrine response triggered by regression of the intraoperative level of anaesthesia.

Accident aigu toxique après bloc du plexus lombaire à la bupivacaïne

Acute toxic accident following lumbar plexus block with bupivacaine. We report the case of a patient who experienced ventricular dysrhythmias and seizure five minutes after the injection of 30 mL of 0.5% bupivacaine with 1:200,000 epinephrine, during a lumbar plexus block performed via the posterior approach described by Winnie. The patient who underwent his total hip arthroplasty was still anaesthetised and under controlled ventilation at the time of bupivacaine administration. Aspiration test performed before injection was negative. Normal cardiac activity and stable haemodynamic condition were restored after one hour of resuscitation including 15 electric shocks and administration of epinephrine (40 mg) and clonidine (300 μg). The patient was discharged without neurologic sequelae after four days in the ICU.

Contralateral but not systemic administration of bupivacaine reduces acute inflammation in the rat hindpaw

The effects of contralateral treatment with local anesthetics following acute hindpaw inflammation were investigated in rats. Inflammation was induced by unilateral injection of either 50 or 100 w l of 1% carrageenan into the right paw. Contralateral injection of either bupivacaine or saline was given immediately before the carrageenan. Hindpaw edema and withdrawal responses to thermal and mechanical stimulation were evaluated after 3, 6 and 24 h. The results showed that the proinflammatory effects of carrageenan were strongest at 6 h after the injection of 100 mul carrageenan with bilaterally decreased withdrawal latencies and ipsilateral edema formation. Contralateral treatment with bupivacaine (1.25, 2.5 or 5 mg/ml) dosedependently reduced nociceptive behavior for 3-24 h. The edema was also reduced at 6 h. No effects on pain-related behavior were observed following systemic administration of bupivacaine. Sciatic nerve ligation on the contralateral side or intrathecal administration of saline significantly reduced the effects of bupivacaine when respectively compared with shamoperation and subcutaneous saline injection. Contralateral treatment with bupivacaine into the knee joint induced the same anti-nociceptive effect as administered into the paw. Our findings indicate that contralateral administration of bupivacaine induces long-lasting anti-nociceptive effects and may serve as a new or complementary treatment approach in acute inflammatory pain conditions.

L2-3 versus T12-L1 Administration of Meperidine and Bupivacaine Using Patient-Controlled Epidural Analgesia after Obstetric and Gynecologic Surgery

L2-3 versus T12-L1 Administration of Meperidine and Bupivacaine Using Patient-Controlled Epidural Analgesia after Obstetric and Gynecologic Surgery

The Neurologic and Adaptive Capacity Score: a systematic review of its use in obstetric anesthesia research.

The Neurologic and Adaptive Capacity Score: a systematic review of its use in obstetric anesthesia research.

Bupivacaine inhibits baroreflex control of heart rate in conscious rats.

Because exposure to intravenously administered bupivacaine may alter cardiovascular reflexes, the authors examined bupivacaine actions on baroreflex control of heart rate in conscious rats. Baroreflex sensitivity (pulse interval vs. systolic blood pressure in ms/mmHg) was determined before, and 1.5 and 15.0 min after rapid intravenous administration of bupivacaine (0.5, 1.0, and 2.0 mg/kg) using heart rate changes evoked by intravenously administered phenylephrine or nitroprusside. The actions on the sympathetic and parasympathetic autonomic divisions of the baroreflex were tested in the presence of a muscarinic antagonist methyl atropine and a beta-adrenergic antagonist atenolol. Within seconds of injection of bupivacaine, mean arterial pressure increased and heart rate decreased in a dose-dependent manner. Baroreflex sensitivity was unaltered after administration of 0.5 mg/kg bupivacaine. In addition, 1 mg/kg bupivacaine at 1.5 min depressed phenylephrine-evoked reflex bradycardia (0.776 +/- 0.325 vs. 0.543 +/- 0.282 ms/mmHg, P < 0.05) but had no effect on nitroprusside-induced tachycardia. Bupivacaine (2 mg/kg), however, depressed reflex bradycardia and tachycardia (phenylephrine, 0.751 +/- 0.318 vs. 0.451 +/- 0.265; nitroprusside, 0.839 +/- 0.256 vs. 0.564 +/- 0.19 ms/mmHg, P < 0.05). Baroreflex sensitivity returned to prebupivacaine levels by 15 min. Bupivacaine (2 mg/kg), in the presence of atenolol, depressed baroreflex sensitivity (phenylephrine, 0.633 +/- 0.204 vs. 0.277 +/- 0.282; nitroprusside, 0.653 +/- 0.142 vs. 0.320 +/- 0.299 ms/mmHg, P < 0.05). In contrast, bupivacaine did not alter baroreflex sensitivity in the presence of methyl atropine. Bupivacaine, in clinically relevant concentrations, inhibits baroreflex control of heart rate in conscious rats. This inhibition appears to involve primarily vagal components of the baroreflex-heart rate pathways.

Initiating Extradural Analgesia during Labour: Comparison of Three Different Bupivacaine Concentrations Used as the Loading Dose

Objective: Potential effects of extradural analgesia on the progress of labour and obstetric outcome are still a matter of concern and the focus of ongoing debates. Despite this, little attention is paid to the initiation of extradural labour analgesia. The objective of this prospective, randomized, double-blind trial was to identify the optimal of three concentrations of bupivacaine used as a loading bolus for initiating extradural analgesia during labour. Methods: Sixty-seven full-term parturients requesting extradural analgesia received either bupivacaine 0.25% (group A), 0.125% (group B) or 0.0625% (group C). Bupivacaine administration was titrated to achieve a pain score ≤1.5 on a 10-cm visual analogue scale (VAS) and was limited to a maximum of 20 ml of the study drug. We recorded the time to achieve a VAS ≤1.5, the total amount of local anaesthetic used, sensory level, maternal and foetal as well as neonatal side effects. Results: The probability of obtaining a VAS pain score ≤1.5 was significantly lower in group C. Although mean times to reach a VAS pain score ≤1.5 were not statistically different, survival curves show a significantly lower probability for reaching this score. Significantly more parturients in group A developed a motor block ≥1 based on using a modified Bromage scoring scale. There were no differences in incidence of maternal hypotension, ephedrine requirements, foetal heart rate abnormalities, mode of delivery and neonatal outcome. Conclusions: Of the three concentrations used in this clinical setting, 0.125% was the most suitable concentration of plain bupivacaine to initiate extradural analgesia in labour. Using 0.25% bupivacaine increased the incidence of motor block, whereas for 0.0625% plain bupivacaine the probability to achieve adequate analgesia was unacceptably low.

Evaluation of bupivacaine-induced muscle regeneration in the treatment of ptosis in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome.

Ptosis is common in patients with mitochondrial disease. Whilst surgical shortening of the levator muscle can mechanically elevate the lid, this procedure does not restore normal movement and leaves patients at risk of corneal exposure due to concomitant ophthalmoparesis. Recent studies have shown that bupivacaine-induced muscle regeneration is capable of reversing the molecular genetic and biochemical defect in patients with mitochondrial myopathies. This study was undertaken to assess the potential of this approach in restoring levator muscle function in patients with mitochondrial disease and ptosis. The levator muscle of one eye in five patients with molecularly genetically confirmed mitochondrial DNA disease and ptosis was directly injected with 3 ml of bupivacaine hydrochloride (0.75%). Levator function was compared before and 3 months after the injection. No objective clinical improvement in levator function was detected following bupivacaine administration. The lack of functional recovery seen in our patients is most likely to result from a failure of bupivacaine to induce sufficient regeneration necessary to improve levator muscle function. This result indicates that consideration now needs to be given to the use of alternative and more potent myotoxic agents capable of inducing a more widespread regenerative response from the endogenous muscle satellite cells which contain low or undetectable amounts of mutant mitochondrial DNA.

Continuous spinal anaesthesia or continuous epidural anaesthesia for post-operative pain control after hip replacement?

Both continuous spinal anaesthesia and continuous epidural anaesthesia are supposed to provide adequate post-operative pain relief. The purpose of this randomized, prospective study was to compare the quality of analgesia, occurrence of side effects and patient satisfaction between spinal and epidural administration of bupivacaine during the first post-operative 72 h. One hundred and two patients scheduled for hip arthroplasty were randomly assigned to one of two groups: Group 1 received continuous spinal anaesthesia for intra-operative and post-operative management, Group 2 received continuous epidural anaesthesia. Immediately after surgery, the continuous spinal anaesthesia-group received a 1-mL bolus (bupivacaine 0.25%), followed by a continuous infusion of 10 mL over 24 h. The continuous epidural anaesthesia-group received a 10-mL bolus (bupivacaine 0.25%), followed by 2 mL h-1. The level of pain was gauged from a verbal rating score and from a visual analogue scale; the degree of motor blockade was recorded using the Bromage score. In the continuous spinal anaesthesia-group 90.2% reported complete analgesia on the verbal rating scale, but only 21.6% of the continuous epidural anaesthesia-group did. The visual analogue scale scores given by the continuous spinal anaesthesia-group were significantly lower than those of the continuous epidural anaesthesia-group. The percentage of patients with a motor block was significantly higher in the continuous spinal anaesthesia-group on the day of surgery and at the first post-operative day. During the first 24 h, nausea and vomiting occurred more often in the continuous epidural anaesthesia-group. The satisfaction was considered excellent in 92.2% of the continuous spinal anaesthesia-group and in 70.6% of the continuous epidural anaesthesia-group. It is concluded that continuous spinal anaesthesia and continuous epidural anaesthesia are effective and safe for post-operative pain relief after hip replacement. Compared with continuous epidural anaesthesia, continuous spinal anaesthesia provides faster onset of pain relief, ensures better analgesia and results in more satisfied patients.

Continuous spinal anaesthesia or continuous epidural anaesthesia for post-operative pain control after hip replacement?

Both continuous spinal anaesthesia and continuous epidural anaesthesia are supposed to provide adequate post-operative pain relief. The purpose of this randomized, prospective study was to compare the quality of analgesia, occurence of side effects and patient satisfaction between spinal and epidural administration of bupivacaine during the first post-operative 72 h. One hundred and two patients scheduled for hip arthroplasty were randomly assigned to one of two groups: Group 1 received continuous spinal anaesthesia for intra-operative and post-operative management, Group 2 received continuous epidural anaesthesia. Immediately after surgery, the continuous spinal anaesthesia-group received a 1-mL bolus (bupivacaine 0.25%), followed by a continuous infusion of 10 mL over 24 h. The continuous epidural anaesthesia-group received a 10-mL bolus (bupivacaine 0.25%), followed by 2 mL h−1. The level of pain was gauged from a verbal rating score and from a visual analogue scale; the degree of motor blockade was recorded using the Bromage score. In the continuous spinal anaesthesia-group 90.2% reported complete analgesia on the verbal rating scale, but only 21.6% of the continous epidural anaesthesia-group did. The visual analogue scale scores given by the continuous spinal anaesthesia-group were significantly lower than those of the continuous epidural anaesthesia-group. The percentage of patients with a motor block was significantly higher in the continuous spinal anaesthesia-group on the day of surgery and at the first post-operative day. During the first 24 h, nausea and vomiting occured more often in the continuous epidural anaesthesia-group. The satisfaction was considered excellent in 92.2% of the continuous spinal anaesthesia-group and in 70.6% of the continuous epidural anaesthesia-group. It is concluded that continuous spinal anaesthesia and continuous epidural anaesthesia are effective and safe for post-operative pain relief after hip replacement. Compared with continuous epidural anaesthesia, continuous spinal anaesthesia provides faster onset of pain relief, ensures better analgesia and results in more satisfied patients.

Continuous epidural administration of midazolam and bupivacaine for postoperative analgesia.

Midazolam has been reported to have a spinally mediated analgesic effect. Clinically, single-shot epidural or spinal administration of midazolam has been shown to have an analgesic effect on perioperative pain. In this study, we investigated the analgesic effect of continuous epidural administration of midazolam with bupivacaine on postoperative pain. Four groups of 20 patients who underwent gastrectomy or cholecystectomy were studied. Continuous epidural infusion of bupivacaine 100 mg (Group C), bupivacaine 100 mg + midazolam 10 mg (Group M10), or bupivacaine 100 mg + midazolam 20 mg (Group M20) in 40 ml per 12 h was started after surgery using the balloon infuser. Group I received intermittent epidural bupivacaine (2.5 mg.ml-1) 6 ml every 2 h. When necessary, an indomethacin suppository and then a single epidural shot of bupivacaine (2.5 mg.ml-1) 6 ml was administered. Blood pressure, heart rate, respiratory rate, analgesic area, analgesia score, and sedation score were monitored for 12 h postoperatively. Memory and frequencies of supplemental analgesia (indomethacin suppositories and epidural bupivacaine) were also checked. Group M20 showed a significantly wider area of pinprick analgesia and better analgesia scores than other groups. The need for rescue analgesics were significantly less in Group M20. Sedation and amnesia were more pronounced in Group M20 than the other groups. Adding midazolam (10 to 20 mg per 12 h) to continuous epidural infusion of bupivacaine for postoperative pain can provide a better analgesia, amnesia and sedation than bupivacaine alone.

Endoscopic Thoracic Sympathectomy for Primary Erythromelalgia in the Upper Extremities

Endoscopic Thoracic Sympathectomy for Primary Erythromelalgia in the Upper Extremities

The Neurotoxicity of Drugs Given Intrathecally (Spinal)

The Neurotoxicity of Drugs Given Intrathecally (Spinal)

Problems of long-term spinal opioid treatment in advanced cancer patients

Epidural and intrathecal techniques are well established techniques in cancer pain. However, several questions remain unresolved. The several problems of long-term spinal opioid treatment in advance cancer patients were reviewed. Indications for the use of spinal opioids include patients treated by systemic opioids with effective pain relief but with unacceptable side effects, or unsuccessful treatment with sequential strong opioid drug trials despite escalating doses. Therefore, the previous aggressive treatment with systemic opioids would leave as failures patients with difficult pain syndromes unresponsive to opioids. The choice of external or totally implanted delivery systems is based on different clinical considerations. The use of externalized tunneled intrathecal catheters has not been associated with higher rates of complications and is easier to place and use at home in debilitated patients late in the course of their disease. The intrathecal administration has a lower incidence of catheter occlusion, lower malfunctioning rate, lower dose requirement, and more effective pain control. Due to the lower daily doses and volumes, intrathecal treatment proved to be more suitable for treatment at home by a continuous infusion than the epidural treatment. Advantages of infusion techniques are more evident when using local anesthetics, since intermittent administration of bupivacaine often results in motor paralysis and hemodynamic instability. Morphine is the opioid of choice. An epidural dose of 10% of the systemic dose is often used. However, intrathecal administration of opioids and bupivacaine may substantially improve pain relief in patients unresponsive to high epidural doses of these drugs, Bupivacaine-induced adverse effects, including sensory deficits, motor complaints, signs of autonomic dysfunction or neurotoxicity have been reported to not occur with bupivacaine doses less than 30–60 mg/day. Adjuvant drugs may further improve analgesia. Different ranges of technical complication rates have been reported in the literature, most of them being associated with epidural catheters. Subcutaneous tunneling and fixation of the catheter, bacterial filters, minimum changes of tubings, careful exit site care weekly, site protection and monitoring of any sign of infection to prevent infection, and training for family under supervision, are recommended. Areas for additional research include the use of spinal adjuvants, the ideal spinal morphine-bupivacaine ratio, methods to improve spinal opioid responsiveness and long-term catheter management with appropriate home care programs.

A randomized, double-blinded trial of preemptive analgesia in laparoscopy

Objective: We tested the hypothesis that local anesthetic administered before skin incision, an example of preemptive analgesia, reduces postoperative pain for women undergoing laparoscopy, as compared with postincisional local anesthetic or placebo. Methods: Patients undergoing diagnostic laparoscopy were randomized to one of three blinded treatment groups. Treatment group A patients received local infiltration of 0.5% bupivacaine at the surgical site before incision and a saline placebo infiltration before incision closure. Treatment group B received the saline placebo before skin incision and bupivacaine after laparoscopy but before closure of the skin incisions. For treatment group C patients, saline was infiltrated as a placebo before and after laparoscopy. All patients underwent a standardized general anesthetic induction and maintenance. Postoperative pain was evaluated using the modified McGill Present Pain Intensity scale. Pain and supplementary analgesic use was compared among the three treatment groups. Results: A total of 57 patients completed the study for analysis. Age, weight, height, race, indication, and operating time did not vary significantly between the three groups. By 24 hours after surgery, patients in treatment group A reported significantly lower pain scores (McGill Present Pain Intensity Scale: 0.5 ± 0.9) than either treatment group B (1.6 ± 1.3) or C (1.3 ± 1.2). Group A patients also could tolerate a significantly longer time delay to their first analgesic medication than patients who received postincisional bupivacaine or than control patients who received no bupivacaine. Conclusion: The preemptive administration of bupivacaine before laparoscopy results in decreased postoperative pain and should allow a more rapid return to normal activities. The popular practice of infiltrating bupivacaine at time of incision closure does not offer any benefit in the control of pain after laparoscopy.

Long-Term Intrathecal (IT) Administration of Opioid and Bupivacaine Relieved Intractable Pain in a Patient with Familial Amyloidosis Polyneuropathy: A Case Report

Introduction. At the present time, there is no reliable method or drug for effective relief of the severe pain caused by the amyloldotic polyneuropathy (AP). Objective. To explore the possibility of relieving this type of pain by intrathecal (IT) infusion of opioid (morphine or buprenorphine), with or without bupivacaine. Patients, Materials and Methods. A 49-year-old male AP patient with Intractable pain in the low back, lower abdomen, and lower extremities. Opioids (up to 20 mg parenteral morphine-eq/day), and epidural injections of morphine (up to 36 mg/day) failed to provide long-term satisfactory pain relief. Therefore, an IT catheter was inserted via the L3-L4 interspace with its tip located at the L1-L2 intervertebral disk. Results. Intermittent IT injections of morphine from 5 to 30 mg per day, for 124 days, and continuous IT infusion of morphine (2-4 mg/ml), combined with bupivacaine (1.0-2.0 mg/ml), in daily rates from 2 to 12 ml (median = 9.5) for another 67 days, were associated with occurrence of seizures, suspected to be caused by the IT morphine. Therefore, the IT morphine was replaced with IT buprenorphine. Thereafter, the pain was treated with IT infusion of buprenorphine (0.06 mg/ml) and bupivacaine (1.25 mg/ml) in daily rates from 4 to 13 ml (median = 5) for another 676 days, until the patient's death, for reasons unrelated to the IT treatment. He experienced satisfactory pain relief with daily doses of IT opioid from 4.5 to 39 mg morphine-eq (median = 19.6 mg) and IT bupivacaine from 0 to 20 (median = 12.5). The mean visual Analog Scores (VASmean), decreased from 7 to 0 (out of 10), the gait improved; and nocturnal sleep increased from 1 to 7-8 hours. Respiratory insufficiency (attributed to an an IT daily dose of ∼ 5 mg morphine) and orthostatic hypotension, pareses, and urinary retention occurring at low doses of (12-18 mg/day) of IT bupivacaine were recorded. The patient had the IT treatment for 867 days, of which 777 days (> 90%) were spent at home. Conclusion. Long-term IT administration of opioid and bupivacaine provided satisfactory long-term pain relief in a patient with refractory pain due to AP.

In vitro and in vivo microdialysis calibration using retrodialysis for the study of the cerebrospinal distribution of bupivacaine

Microdialysis coupled to HPLC was used to study the disposition of local anesthetics in the cerebrospinal fluid (CSF) because of the difficulty in sampling CSF. A retrodialysis method for the microdialysis calibration was investigated in vitro and in vivo. Calibration by retrodialysis was simultaneously validated through the use of the zero net flux method. Two local anesthetics (bupivacaine and ropivacaine), which differ structurally by only one methyl group, were respectively utilized as substance of interest and as internal standard. Different parameters were tested in vitro to compare the relative recovery ( RR) of bupivacaine and the relative loss ( RL) of ropivacaine. Several flow rates were tried to select an optimal in vivo flow rate (1 μl/min). The RR and RL values were not influenced by the variation of bupivacaine concentration. A significant variability among different probes within a batch was established ( RR ranging from 41.1–65.3%; RL ranging from 30.7–61.0%). The K-factor values, defined as RL ropivacaine/ RL bupivacaine, were calculated in vitro and in vivo. This ratio decreased in vivo but was constant ( K in vitro=1.06±0.04, K in vivo=0.87±0.03). The extracellular tissue concentration of the compound of interest was given by C= C in dialysate×( K/ RL). Following in vivo implantation in rabbit CSF during 4 h, the probes were tested again in vitro and no deterioration of probe during the in vivo experiment was found. After administration of bupivacaine in the epidural space of rabbits, plasma and microdialysis CSF samples were simultaneously collected. Plasma and CSF disposition of bupivacaine displayed different kinetics. The maximum CSF concentration of B averaged 394±170 μg ml −1, with a mean T max of 3.8±1.8 min. The maximum plasma concentration of B averaged 0.44±0.09 μg ml −1 with a mean T max occurring at 1 min. Microdialysis, combined with accurate calibration, should be a reliable technique to gain further insight in the spinal disposition of local anesthetics.

Dose-related cardiovascular effects of amrinone and epinephrine in reversing bupivacaine-induced cardiovascular depression.

To ascertain the efficacy of amrinone and epinephrine in reversing bupivacaine-induced cardiovascular depression, we investigated the time course of recovery of cardiac function with 3 doses of both agents after bupivacaine administration. In sevoflurane-anaesthetized dogs, bupivacaine was infused intravenously at 1 mg.kg-1.min-1 until mean arterial pressure fell to 60 mmHg or less. The 3 doses of amrinone (1, 2, and 4 mg.kg-1) or the 3 doses of epinephrine (2, 5, and 10 micrograms.kg-1) were administered as a bolus in randomized order in each dog. Amrinone improved maximum left ventricular dP/dt, a time constant of left ventricular isovolemic relaxation and cardiac index persistently and dose-relatedly. Amrinone increased heart rate and decreased left ventricular end-diastolic pressure and systemic vascular resistance index. Amrinone at 1 and 2 mg.kg-1 significantly increased mean arterial pressure, but amrinone at 4 mg.kg-1 did not. Epinephrine increased mean arterial pressure, maximum left ventricular dP/dt, and systemic vascular resistance dose-relatedly. The duration of action of epinephrine, peaking at 1 min and subsequently decreasing by 10 min after administration, did not differ among the groups. Epinephrine at all doses failed to improve a time constant of left ventricular isovolemic relaxation and cardiac index. ECG evidence of serious ventricular dysrhythmias was seen in 1 out of 6 dogs after administrating each dose of amrinone and in 3, 3 and 5 out of 6 dogs after administrating 2, 5 and 10 micrograms.kg-1 of epinephrine, respectively. Bolus amrinone may have a certain efficacy in reversing bupivacaine-induced cardiovascular depression, and improving cardiac contractility and relaxation dose-relatedly. In contrast to amrinone, bolus epinephrine remains indispensable for resuscitation, causing a rapid, massive, transient and dose-related rise in blood pressure. However, the use of amrinone may be limited predominantly by a decrease in systemic vascular resistance, while the use of epinephrine may be limited predominantly by the generation of serious ventricular dysrhythmias and lack of effectiveness on cardiac index and on cardiac relaxation.