Administration Of Bupivacaine Research Articles

Umbilical artery flow velocity waveforms during spinal anesthesia

The umbilical artery Doppler flow velocity waveform was recorded during spinal anaesthesia prior to elective caesarean section in 15 uncomplicated pregnancies. Although spinal anaesthesia was associated with a significant fall in maternal systolic and diastolic blood pressure, there was no change in the umbilical artery Pulsatility Index either after preloading the maternal circulation with 750–1000 ml of Hartman's solution or for the first 15 min after subarachnoid injection of 0.5% bupivacaine. The fetal heart rate fell after preloading the maternal circulation, but was unchanged by the administration of bupivacaine. There was a weak negative correlation between fetal heart and the umbilical artery Pulsatility Index. These observations suggest that in normal pregnancy, spinal anaesthesia has no detrimental effect on the umbilical artery Pulsatility Index.

Analgesia in Dogs after Intercostal Thoracotomy A Comparison of Morphine, Selective Intercostal Nerve Block, and Interpleural Regional Analgesia with Bupivacaine

Three postoperative analgesic protocols were assigned randomly to 24 healthy dogs after thoracotomy at the left fourth intercostal space. Morphine was administered parenterally to eight dogs after tracheal extubation; selective intercostal nerve blocks with bupivacaine hydrochloride and epinephrine were administered to eight dogs before closure of the thorax; and bupivacaine hydrochloride and epinephrine were administered through an interpleural catheter to eight dogs after tracheal extubation. Heart rate, respiratory rate, rectal temperature, hematocrit, plasma protein, blood gas, and pain score evaluations were recorded before surgery and 30 minutes, 1 hour, 2 hours, and 3 hours after extubation. Morphine caused significant decreases in blood pH and blood oxygen tensions, and significant increases in carbon dioxide tensions. Dogs treated with intercostal nerve blocks had no significant changes in these parameters, and dogs treated with interpleural bupivacaine had significant decreases in blood oxygen tension. All dogs had significant decreases in rectal temperature, and hypothermia was prolonged after morphine. Analgesia was initially adequate in most dogs, but some dogs in each treatment group had recurrence of pain and were treated with interpleural bupivacaine. One dog developed pneumothorax. Interpleural administration of bupivacaine produced analgesia equal to that produced by systemic administration of morphine or selective intercostal nerve block with bupivacaine. Bupivacaine was easily readministered through an interpleural catheter. Respiratory compromise was less in dogs treated with bupivacaine than in dogs treated with morphine. After intercostal thoracotomy, interpleural bupivacaine provided prolonged analgesia with fewer blood gas alterations than morphine.

A randomised double‐blind study of interpleural analgesia after cholecystectomy

Continuous interpleural analgesia provided by 4 hourly injections of 20 ml bupivacaine 0.5% with adrenaline 5 micrograms/ml was compared with placebo in a randomised, double-blind study after cholecystectomy. All patients self-administered intravenous morphine using a patient-controlled analgesia device. There was a highly significant difference in mean morphine consumption between the groups (72 mg as compared with 22 mg). Visual analogue pain scores tended to be lower in the bupivacaine group throughout and this was significant at 2 hours. Respiratory function measurements were not significantly different between the groups. The mean peak venous plasma bupivacaine concentration after the sixth dose was 3.03 micrograms/ml and no symptoms suggestive of local anaesthetic toxicity occurred. It is concluded that this regimen can provide effective and continuous analgesia after cholecystectomy and that combined administration of interpleural bupivacaine and systemic morphine is more effective than morphine alone in the immediate postoperative period. The doses of bupivacaine required for optimal use of the technique lead to significant total plasma bupivacaine concentrations within 24 hours.

Cerebrospinal norepinephrine concentrations and the duration of epidural analgesia

This study was performed to determine whether the addition of norepinephrine to local anaesthetics prolongs epidural analgesia in man. In addition, cerebrospinal fluid norepinephrine (NE) concentrations were measured. In the first part of the study, epidural catheters were inserted in 14 patients before herniotomy. Mepivacaine, 1.5 per cent (0.35 ml.kg-1), was administered and norepinephrine (5 micrograms.ml-1) was added in seven patients. The duration of anaesthesia was prolonged from 54 +/- 11 min to 83 +/- 12 min (P less than 0.05) and CSF NE concentrations increased from 68 +/- 12 pg.ml-1 to 336 +/- 85 pg.ml-1 in the NE group (P less than 0.01). In the second part, eight patients with herpetic neuralgia received epidural analgesia at the fourth to eighth thoracic interspace, using bupivacaine 0.25 per cent, with and without NE. The CSF NE concentrations in this group were greater than in the surgical patients before operation and increased from 254 +/- 58 to 406 +/- 58 pg.ml-1 30 min after administration of bupivacaine with NE. The duration of pain relief was prolonged with NE. These results suggest that adding NE to local anaesthetics prolongs epidural analgesia. Moreover, NE concentrations in surgical patients increased to levels similar to those found in patients suffering from herpetic analgesia. This suggests that the increase of CSF NE in chronic pain states has an antinociceptive effect.

Effect of Epidural Anesthesia for Cesarean Delivery on Maternal Femoral Arterial and Venous, Uteroplacental, and Umbilical Blood Flow Velocities and Waveforms

13 women with uncomplicated singleton pregnancies receiving epidural anesthesia for elective cesarean section underwent pulsed Doppler determination of maternal, uteroplacental and umbilical circulations. Data accumulated included resistance and pulsatility indices in the umbilical circulation, peak and mean velocities in the maternal femoral artery, mean femeral vein velocity, venous and arterial diastolic diameters, maternal BP and HR, FHR, and resistance and pulsatility indices in the uteroplacental circulation. Data were obtained before and after administration of epidural bupivacaine. All measurements were performed after prehydration and in the left semirecumbent position.

Cocaine and local anesthetics: Stimulant activity in rats with nigral lesions

Cocaine and several other local anesthetics were tested for their ability to induce rotational behavior in rats with unilateral 6-hydroxydopamine lesions of substantia nigra. Acute administration of bupivacaine, chloroprocaine, etidocaine, lidocaine, mepivacaine, procaine or tetracaine failed to induce active rotation in this sensitive assay of dopamine agonist activity. On the other hand, cocaine or dimethocaine treatment induced active rotation directed ipsilaterally to the lesioned side, indicating indirect dopamine agonist activity. Repeated administration of cocaine or dimethocaine at 1-week intervals resulted in increased rotational response (i.e., sensitization) while there was no suggestion of sensitization or induction of rotational behavior after weekly repeated administration of procaine or tetracaine. Daily administration of mepivacaine, procaine or tetracaine for 5 days also failed to induce rotation. Dimethocaine thus was found similar to cocaine and different from the other local anesthetics tested both in terms of frank stimulant activity and development of sensitization upon repeated administration.

Continuous High Thoracic Epidural Administration of Bupivacaine with Sufentanil or Nicomorphine for Postoperative Pain Relief After Thoracic Surgery

Continuous High Thoracic Epidural Administration of Bupivacaine with Sufentanil or Nicomorphine for Postoperative Pain Relief After Thoracic Surgery

Interpleural Administration of Bupivacaine After Cholecystectomy

Interpleural Administration of Bupivacaine After Cholecystectomy

EXTRADURAL ADMINISTRATION OF BUPIVACAINE: PHARMACOKINETICS AND METABOLISM IN PREGNANT AND NON-PREGNANT WOMEN

We found a similar time (about 0.4 h) to maximum serum concentration after extradural administration of bupivacaine 1.78 (SD 0.27) mg kg-1 to six pregnant patients at term, 1.58 (0.13) mg kg-1 to six women younger than 65 yr and 1.50 mg kg-1 to six women older than 65 yr. There were no significant differences in terminal half-life. No unconjugated 4'-hydroxy-bupivacaine was detected in the serum and urine of pregnant patients, in contrast with the other groups. The pregnant patients had significantly greater serum concentrations of the N-dealkylated metabolite, N-desbutyl-bupivacaine (DBB), than the non-pregnant groups. In contrast with 4'-hydroxy-bupivacaine, no conjugated forms of bupivacaine and desbutyl-bupivacaine were detected in urine. The mean total urinary excretion of bupivacaine and its metabolites and their conjugates varied between 2.46 and 3.22% of the total dose administered in the three patient groups, indicating that both 4'-hydroxylation and N-dealkylation are minor metabolic pathways in man.

Clinical Pharmacokinetics After Repeated Intrapleural Bupivacaine Administration

Patients (n = 14) who underwent thoracotomy during surgery of the oesophagus for cancer received an initial intrapleural dose of 10 ml bupivacaine hydrochloride 2.5 mg/ml followed by repeated administration every 8 hours from the first to the fourth postoperative day. The mean (+/- SD) peak plasma drug concentration (Cmax) [352 +/- 120 micrograms/L], time to peak (tmax) [0.83 +/- 0.51 h], and first-order absorption rate constant (ka) [5.46 +/- 4.95 h-1] after the twelfth dose were significantly different from the Cmax (206 +/- 81 micrograms/L), tmax (1.8 +/- 1.2h), and ka (1.8 +/- 1.47 h-1) determined after the first dose. Half-life (3.5 +/- 2.2h) and mean concentration (204 +/- 105 micrograms/L) were not significantly different on the fourth day from those on the first (4.1 +/- 2.6h and 142 +/- 71 micrograms/L, respectively). No sharp peak corresponding to systemic toxicity and no accumulation could be expected with these low doses, administered at short intervals and providing good pain relief in this surgical series.

Changes in Cardiac Output During Epidural Anaesthesia for Caesarean Section

Summary Serial haemodynamic investigations were performed in 20 women who had epidural anaesthesia before elective Caesarean section. Cardiac output was measured by Doppler and cross-sectional echocardiography at the aortic valve. Measurements were performed after preloading the circulation with Ringer lactate solution (mean volume 805 ml) and then 10, 20, 30 and 40 minutes after administration of 0.5% bupivacaine. Preloading increased mean stroke volume from 84 to 94 ml and mean cardiac output from 7.01 to 7.70 litres/minute. Relative to basal values, mean arterial pressure decreased in all subjects after administration of bupivacaine (mean –14%, range –1 to –33%). Five subjects were given ephedrine because of hypotension. In three of these subjects hypotension was associated with a marked decrease in cardiac output. No significant changes in arterial blood pressure or cardiac output were demonstrated relative to basal values in the remaining 15 subjects. Ephedrine induced consistent increases in blood pressure and cardiac output.

Flare reaction following caudal analgesia

The following case reports describe obvious and marked vascular changes over the S3 dermatome in two children following the administration of bupivacaine 0.125 per cent via the caudal route. These flare reactions were typical of an axon reflex. Vasodilatation in these two case reports could have been mediated by direct stimulation of the S3 routes by the local anaesthetic solution.

In Vitro Study on Mechanisms of Bupivacaine-Induced Depression of Myocardial Contractility

Although several mechanisms have been proposed to explain bupivacaine cardiotoxicity, the predominant effect remains to be determined. In this study, we used an isolated rabbit right atrial model that reproduces the effects on inotropic and chronotropic functions induced by 0.5 micrograms/mL bupivacaine; then we tried to counteract these events by electrical stimulation or by addition of CaCl2 or adenosine triphosphate (ATP) to the bathing solution. Contractile force was dramatically depressed by bupivacaine alone (-68%), even when the preparation was paced (-59%). CaCl2 partially counteracted this decrease (-37%). Inotropic function was almost completely restored (-9%) when ATP was added before administration of bupivacaine. Inhibition of energy metabolism seems to be a major explanation for bupivacaine cardiotoxicity.

Interaction of intravenous diazepam and bupivacaine in conscious dogs.

The cardiac and hemodynamic effects of bupivacaine, diazepam and their coadministration were evaluated in six mongrel dogs chronically instrumented for recording of mean arterial pressure (MAP), left ventricular (LV) pressure, and cardiac output (CO, electromagnetic flow probe around the ascending aorta). LVdP/dt was derived from the LV pressure signal, and its positive peak was used as an index of myocardial contractility. Heart rate (HR), RR, PR and QT intervals were measured from ECG. At weekly intervals, each dog received in a random order one of the following treatments: (1) saline as control, (2) diazepam (0.2 mg/kg, intravenous, bolus), (3) bupivacaine (0.4 mg/kg intravenous bolus, followed by 15 micrograms/kg/minute, during 30 minutes), and (4) a combination of diazepam and bupivacaine, as in (2) and (3), respectively. Despite its intrinsic cardiodepressant effects, bupivacaine induced a delayed (30-minute) compensatory increase in HR (+ 11%, p less than 0.05) and LVdP/dt (+ 10%, p less than 0.05). Diazepam decreased systemic vascular resistance (SVR; -16%, p less than 0.05) with concomitant increases in HR and CO. After diazepam pretreatment, LVdP/dt did not rise after bupivacaine administration, whereas SVR decreased (-14%, p less than 0.05) and HR increased (+19%, p less than 0.05). The QT-RR relationship remained unchanged regardless of the treatment administered. Thus, diazepam might blunt the compensatory effects of bupivacaine on cardiac function and may decrease the margin of safety of this local anesthetic agent during major neural blockade procedure.

Protective effect of a specific platelet activating factor antagonist, BN 52021, on bupivacaine-induced cardiovascular impairments in rats

Administration of the local anaesthetic bupivacaine (1 · 5 or 2 mg/kg, i.v.) to rats elicited a marked decrease of mean arterial blood pressure (MBP) and heart rate (HR) leading to death (in 67% or 90% of animals respectively). Intravenous injection of the specific platelet-activating factor (PAF) antagonist BN 52021 (10 mg/kg), 30 min before bupivacaine administration (2 mg/kg i.v.) suppressed both the decrease of MBP and HR. In contrast, doses of 1 mg/kg BN 52021 given 30 min before or 10 mg/kg administered 5 min before i.v. injection of bupivacaine were ineffective. When BN 52021 (20 mg/kg i.v.) was injected immediately after bupivacaine (2 mg/kg), a partial reversion of the decrease of MBP and HR was observed, whereas the dose of 10 mg/kg was ineffective. A partial recovery of bupivacaine-induced ECG alterations was observed after pretreatment of the rats with BN 52021. Since the administration of BN 52021, at all doses studied, did not alter MBP and HR at the doses used, the bulk of these results clearly demonstrate a protective action of BN 52021, a specific antagonist of PAF, against bupivacaine-induced cardiovascular toxicity. Thus, consistent with its direct effect on heart, PAF appears to be implicated in bupivacaine-induced cardiovascular alterations.

Continuous high thoracic epidural administration of bupivacaine with sufentanil or nicomorphine for postoperative pain relief after thoracic surgery.

In a prospective study, 40 patients who had undergone thoracotomy for lung resection were investigated. During operation, all patients received intravenous anesthesics, halothane and an initial dose of bupivacaine 0.5% with epinephrine 5 micrograms.ml-1 (5 to 10 ml) by thoracic epidural catheter. One hour after the initial dose of bupivacaine 0.5% with epinephrine, patients were divided in two groups for analgesia, the sufentanil group (50 micrograms sufentanil in 60 ml bupivacaine 0.125%) or the nicomorphine group (3 mg nicomorphine in 60 ml bupivacaine 0.125%) by a continuous epidural infusion (5 to 10 ml.h-1) for three days. Cardiovascular differences between the sufentanil group and the nicomorphine group were not statistically significant per- or postoperatively. The minimum respiratory frequency on either Day 1, 2, or 3 was 12 breaths.min-1 in the sufentanil group, corresponding to a PaCO2 of 32 mmHg, and 11 breaths.min-1, corresponding to a PaCO2 of 41 mmHg in the nicomorphine group. On Day 1, the PaCO2 in the sufentanil group was significantly lower (p less than 0.01), but in both groups the PaCO2 on Day 1 was significantly higher than the preoperative value. An inverse visual analogue pain scale (0 to 10 IVAS) showed mean scores above 7.5 for all patients during the three days. Scoring pain relief during exercise showed a significant difference in favor of the sufentanil group on Days 1, 2, and 3 (p less than 0.0008). The mean plasma bupivacaine level doubled every day, 138 ng.ml-1 on Day 1, 290 ng.ml-1 on Day 2, and 596 ng.ml-1 on Day 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Interpleural Administration of Bupivacaine after Cholecystectomy: A Comparison with Intercostal Nerve Block

Pethidine requirements and verbal pain scores were recorded in 36 patients after cholecystectomy via subcostal incision. All patients also received 20 ml 0.5% bupivacaine with adrenaline 1/200,000. Group 1 (12 patients) received unilateral intercostal nerve blocks. Interpleural catheters were inserted through the 8th intercostal space in the remaining patients; 12 received local anaesthetic via the catheter immediately after surgery (Group 2) and 12 were given local anaesthetic at three hours (Group 3). Small asymptomatic pneumothoraces were noted on chest X-ray in six of the 24 patients with interpleural catheters. Both types of local anaesthesia produced lower pain scores than pethidine alone (P less than 0.05) with 25% of intercostal nerve blocks and 63% of interpleural catheters requiring no pethidine in the following three hours. The provision of catheter 'top-ups' between six and 18 hours after surgery also resulted in lower pain scores and a reduction in pethidine requirements (P less than 0.05).

Changes in cardiac output during epidural anaesthesia for Caesarean section

Serial haemodynamic investigations were performed in 20 women who had epidural anaesthesia before elective Caesarean section. Cardiac output was measured by Doppler and cross-sectional echocardiography at the aortic valve. Measurements were performed after preloading the circulation with Ringer lactate solution (mean volume 805 ml) and then 10, 20, 30 and 40 minutes after administration of 0.5% bupivacaine. Preloading increased mean stroke volume from 84 to 94 ml and mean cardiac output from 7.01 to 7.70 litres/minute. Relative to basal values, mean arterial pressure decreased in all subjects after administration of bupivacaine (mean - 14%, range - 1 to - 33%). Five subjects were given ephedrine because of hypotension. In three of these subjects hypotension was associated with a marked decrease in cardiac output. No significant changes in arterial blood pressure or cardiac output were demonstrated relative to basal values in the remaining 15 subjects. Ephedrine induced consistent increases in blood pressure and cardiac output.

Epidural diamorphine and bupivacaine in labour

A double-blind randomised study was performed to assess the analgesic effect of epidural diamorphine, administered with bupivacaine, on primigravid women in labour. Fifty patients received 0.25% bupivacaine 10 ml via the epidural catheter as their initial dose; patients in Group 1 received diamorphine 5 mg with the bupivacaine. A 0.1% bupivacaine infusion was started at 10 minutes and bolus doses of bupivacaine were given if required. There was a significant reduction in rate of bupivacaine administration, pain scores at 20 and 30 minutes, number of supplements required, and degree of motor blockade in the diamorphine group.

Failure of epidural opioid to control cancer pain in a patient previously treated with massive doses of intravenous opioid

A patient with disseminated cancer pain failed to obtain pain relief despite the intravenous infusion of hydromorphone at a rate equivalent to over 7 g of morphine/day. Temporary pain relief occurred with an epidural injection of the local anesthetic lidocaine. Subsequently, the patient failed to obtain pain relief with a dose of epidural hydromorphone equivalent to approximately 3 g of morphine epidurally/day. At this time a syndrome of agitation, sweating, tachycardia and severe muscle cramps developed in the lower half of the body. After eliminating the possibility of spinal cord compression by diagnostic CT scanning, the patient was treated by reducing the dose of hydromorphone and adding local anesthetic, which provided pain relief but did not eliminate the severe muscle spasms and other symptoms. The addition of oral clonidine followed by clonidine dermal patch rapidly and completely eliminated the other symptoms, suggesting that the response was due to too rapid withdrawal of opioid. Maintenance of pain relief required the simultaneous administration of epidural bupivacaine and hydromorphone. A low-dose infusion of epidural bupivacaine was continued for more than 3 weeks and during this entire period the patient showed no evidence of motor or sympathetic block.