Liposomal Bupivacaine: Extended Duration Nerve Blockade Using Large Unilamellar Vesicles that Exhibit a Proton Gradient

Background: There is a clinical requirement for longer-acting local anesthetics, particularly for the management of postoperative and chronic pain. In this regard, liposomes have been suggested to represent a potentially useful vehicle for sustained drug release after local administration. In the current study, the authors used a transmembrane pH gradient to efficiently encapsulate bupivacaine within large unilamellar vesicles. They report on the kinetics of drug uptake and release and the duration of nerve blockade.

Methods: The rate and extent of bupivacaine uptake into large unilamellar vesicles that exhibit a pH gradient (interior acidic) were determined and compared to drug association with control liposomes that did not exhibit a proton gradient. In subsequent studies, researchers examined the kinetics of bupivacaine release from these liposome systems in vitro. Using the guinea pig cutaneous wheal model, the rate of clearance of the liposome carrier was monitored after intradermal administration, using a radiolabelled lipid marker, and the duration of nerve blockade produced by free and liposomal bupivacaine was compared.

Results: Bupivacaine was rapidly and efficiently accumulated within liposomes that exhibited a pH gradient (interior acidic) with trapping efficiencies of 64-82% of total drug, depending on the initial bupivacaine:phospholipid ratio. Little uptake was seen, however, for control vesicles that did not exhibit a transmembrane proton gradient. Using an in vitro model of drug clearance, liposomally encapsulated bupivacaine was found to be slowly released for a longer period of time compared with either the free drug or bupivacaine associated with control (no pH gradient liposomes). In the guinea pig cutaneous wheal model, more than 85% of the liposomal carrier was found to remain at the site of administration for 2 days. The sustained drug release afforded by liposomes that exhibited a pH gradient resulted in an increase in the duration of nerve blockade of as much as threefold compared with either the free drug or bupivacaine in the presence of control (no pH gradient) liposomes. Recovery of half maximal response (R2.5) after administration of 0.75% free bupivacaine, for example, was approximately 2 h, whereas the same dose of bupivacaine in pH gradient liposomes exhibited a R2.5 of approximately 6.5 h.     

Uptake and distribution of bupivacaine and morphine after intrathecal administration in parturients: effects of epinephrine.

This study examines the plasma pharmacokinetics of bupivacaine and morphine and the urinary excretion of morphine administered for spinal anesthesia for cesarean section. Patients received 12 mg of hyperbaric bupivacaine and 0.6 mg of morphine with either 0.2 mL of normal saline (plain, n = 15) or 0.2 mg of epinephrine (n = 15). Venous blood and urine were collected at 0, 0.25, 0.5, 1, 2, 3, 6, 12, and 24 h. Total and unconjugated morphine (UCM) in plasma and urine were measured using radioimmunoassay, and plasma bupivacaine was measured by gas chromatography. Results were expressed as mean +/- SE and analyzed using Student's t-test at P less than 0.05. In the epinephrine group, plasma bupivacaine peaked at 15 min and remained approximately 30% higher (P less than 0.05) at 0.25, 0.5, and 1 h than in the plain group, which peaked at 30 min. Although UCM peaked at 3 h in both groups, the plasma levels remained approximately 66% lower in the epinephrine group. In the epinephrine group, bupivacaine had a smaller volume of distribution at steady state, and morphine had a more rapid clearance, shorter t1/2 beta, and smaller area under the curve compared with the plain group (P less than 0.05). Only 45% +/- 5% and 31% +/- 3% of morphine was recovered in the urine in the plain and epinephrine group, respectively (P less than 0.05). In conclusion, epinephrine added to a bupivacaine-morphine mixture increases the initial systemic uptake of bupivacaine and decreases the absorption and urinary excretion of morphine from the intrathecal space.     

Wound infiltration with liposomal bupivacaine prolongs analgesia in rats

Background: Wound infiltration with local anesthetics does not reliably produce satisfactory postoperative analgesia, and the dose of local anesthetic which may be safely administered is limited by the potential for systemic toxicity. This study evaluated the efficacy of a slow-release liposomal bupivacaine formulation on duration of wound analgesia.
Methods: Multilammelar liposomes containing bupivacaine were assessed using a rat paw wound model. Twenty-four hours after surgical incision, paw wounds determined to be hyperalgesic to graded force testing with von Frey hairs were infiltrated with 0.3 ml of 2% liposomal bupivacaine, 0.5% plain bupivacaine, saline, or 'empty' (normal saline) liposomes (n=6/group). The duration of analgesia was measured. The 0.5% plain concentration was chosen because, in preliminary experiments, larger doses were often fatal. Analgesia duration was compared using Mann-Whitney U test at P < 0.05. In other rats, plasma bupivacaine levels after wound infiltration with either 2% liposomal formulation or 0.5% plain formulation were assessed (n=8/group).
Results: The mean duration of analgesia was 23+/-3 (SD) min for plain bupivacaine and 180+/-30 min for liposomal bupivacaine. No wound analgesia was detected in animals given normal saline or 'empty' liposomes. Plasma bupivacaine levels tended to be lower after liposomal than plain bupivacaine.
Conclusions: The 8-fold increase in duration of wound analgesia and the lower plasma levels seen with the liposomal formulation are explained by gradual drug release from the liposomal depot. These results may have important implications for achieving safe and effective analgesia with wound infiltration techniques in humans.     

Tetrodotoxin-induced conduction blockade is prolonged by hyaluronic acid with and without bupivacaine

BACKGROUND: In isolated nerves, tetrodotoxin (TTX) blocks nerve conduction longer than bupivacaine. In vivo, however, both substances block nerve conduction to an equal duration, presumably because the hydrophilic TTX binds only weakly to the perineural tissue. High molecular weight hyaluronic acid (HA) prolongs the action of local anaesthetics several-fold. We tested whether admixture of HA enhances the binding of TTX to the perineural tissue and thus induces an ultra-long conduction block after a single application. METHODS: In 12 anaesthetized rabbits, the minimal blocking concentrations of TTX, TTX and HA (TTX/HA) and bupivacaine with HA (bupivacaine/HA) were determined by blocking the natural spike activity of the aortic nerve. In 18 other animals, equipotent concentrations of either TTX, TTX/HA or TTX/bupivacaine/HA were applied topically to the aortic nerve. After disappearance of the spike activity, the wound was closed to simulate the clinical situation of a single shot nerve block. The time until recovery of spike activity was determined. The nerves were examined for signs of neurotoxicity 24 h after the application of the drugs. Data are presented as means +/- SD and compared by ANOVA and Student's t-test for unpaired data. RESULTS: The conduction block by TTX/bupivacaine/HA (10.1 +/- 1.9 h) or TTX/HA (9.3 +/- 1.0 h) was significantly longer than that of plain TTX (7.9 +/- 1.0 h). Neurotoxicity was not observed. CONCLUSIONS: Both HA and HA/bupivacaine prolong the TTX-induced conduction blockade of the aortic nerve of rabbits in vivo. No signs of neurotoxicity were observed.     

Tetrodotoxin-induced conduction blockade is prolonged by hyaluronic acid with and without bupivacaine

BACKGROUND: In isolated nerves, tetrodotoxin (TTX) blocks nerve conduction longer than bupivacaine. In vivo, however, both substances block nerve conduction to an equal duration, presumably because the hydrophilic TTX binds only weakly to the perineural tissue. High molecular weight hyaluronic acid (HA) prolongs the action of local anaesthetics several-fold. We tested whether admixture of HA enhances the binding of TTX to the perineural tissue and thus induces an ultra-long conduction block after a single application. METHODS: In 12 anaesthetized rabbits, the minimal blocking concentrations of TTX, TTX and HA (TTX/HA) and bupivacaine with HA (bupivacaine/HA) were determined by blocking the natural spike activity of the aortic nerve. In 18 other animals, equipotent concentrations of either TTX, TTX/HA or TTX/bupivacaine/HA were applied topically to the aortic nerve. After disappearance of the spike activity, the wound was closed to simulate the clinical situation of a single shot nerve block. The time until recovery of spike activity was determined. The nerves were examined for signs of neurotoxicity 24 h after the application of the drugs. Data are presented as means +/- SD and compared by ANOVA and Student's t-test for unpaired data. RESULTS: The conduction block by TTX/bupivacaine/HA (10.1 +/- 1.9 h) or TTX/HA (9.3 +/- 1.0 h) was significantly longer than that of plain TTX (7.9 +/- 1.0 h). Neurotoxicity was not observed. CONCLUSIONS: Both HA and HA/bupivacaine prolong the TTX-induced conduction blockade of the aortic nerve of rabbits in vivo. No signs of neurotoxicity were observed.     

Epidural bupivacaine suppresses local glucose utilization in the spinal cord and brain of rats

Using the 2-[14C]deoxyglucose method, the effects of analgesic doses of epidural bupivacaine (300 micrograms) on local spinal cord glucose utilization (SP-LGU) of the cervical, thoracic, and lumbar regions and local cerebral glucose utilization (BR-LGU) in 38 brain structures were examined in conscious rats. In addition, the effects of intramuscular bupivacaine (300 micrograms) and the spinal cord transection (T2) were examined to determine whether the induced metabolic changes, if any, are related to the drug's systemic effect and/or deafferentation. Lumbar epidural bupivacaine sufficient to produce analgesia decreased SP-LGU in the thoracic (18-28%) and lumbar (21-29%) spinal cord but not in the cervical cord. Epidural bupivacaine decreased BR-LGU (15-26%) in 35 of 38 structures examined. With intramuscular bupivacaine, SP-LGU remained unchanged in almost all regions, while BR-LGU was significantly decreased (11-23%) in 23 structures. Plasma concentrations of bupivacaine in the epidural and intramuscular groups were comparable. With spinal cord transection alone, SP-LGU significantly decreased with varying degrees depending on the structure examined, but BR-LGU did not decrease in 36 of 38 structures examined. These results indicate that analgesic doses of epidural bupivacaine decrease SP-LGU, probably reflecting decreased neuronal activity of the spinal cord, and that reduced BR-LGU by epidural bupivacaine is most likely due to the drug's systemic effect rather than deafferentation.     

EFFECT OF BARICITY ON SPINAL ANAESTHESIA WITH BUPIVACAINE

In a double-blind study of spinal anaesthesia with 0.5% bupivacaine3 ml with no glucose, 5% glucose or 8% glucose all three solutionsgave consistently good nerve blocks. The hyperbaric solutions(5% and 8% glucose) produced a greater cephalad spread and weresuitable for lower abdominal surgery, whereas the plain solution(no glucose) seldom affected the thoracic nerves. Cardiovascularchanges were more marked with the hyperbaric solutions but onlynecessitated treatment on two occasions. The duration of blockwas not affected by baricity and was in the range 140–160min.     

SPINAL ANAESTHESIA WITH HYPOBARIC 0.19% OR PLAIN 0.5% BUPIVACAINE

Hypobaric 0.19% bupivacaine (plain 0.5% bupivacaine 3 ml + distilledwater 5 ml) was compared with 0.5% plain bupivacaine 3 ml forspinal anaesthesia in 29 healthy patients undergoing orthopaedicsurgery of the lower extremities. The solutions were injectedat the L3–4 interspace in 40 s, and patients were keptsitting for 2 min after injection. The mean maximal cephaladspread of sensory block was to the T1 segment (SD 3.6) and toT8 (4.1) in the hypobaric and plain bupivacaine groups, respectively(P < 0.0001). The study was interrupted after observing thesensory block of the 29th patient (hypobaric bupivacaine) spreadto C2 within 5 min of injection. In most patients, the hypobaricbupivacaine block affected the upper thoracic nerves, and inthree patients the cervical nerves also. The high levels ofblock were accompanied by marked hypotension. The extensivespread of the blocks makes this hypobaric spinal anaesthesiatechnique unsuitable for routine use.     

Perineural Administration of Dexmedetomidine in Combination with Bupivacaine Enhances Sensory and Motor Blockade in Sciatic Nerve Block without Inducing Neurotoxicity in Rat

Background: The current study was designed to test the hypothesis that high-dose dexmedetomidine added to local anesthetic would increase the duration of sensory and motor blockade in a rat model of sciatic nerve blockade without causing nerve damage.

Methods: Thirty-one adult Sprague-Dawley rats received bilateral sciatic nerve blocks with either 0.2 ml bupivacaine, 0.5%, and 0.5% bupivacaine plus 0.005% dexmedetomidine in the contralateral extremity, or 0.2 ml dexmedetomidine, 0.005%, and normal saline in the contralateral extremity. Sensory and motor function were assessed by a blinded investigator every 30 min until the return of normal sensory and motor function. Sciatic nerves were harvested at either 24 h or 14 days after injection and analyzed for perineural inflammation and nerve damage.

Results: High-dose dexmedetomidine added to bupivacaine significantly enhanced the duration of sensory and motor blockade. Dexmedetomidine alone did not cause significant motor or sensory block. All of the nerves analyzed had normal axons and myelin at 24 h and 14 days. Bupivacaine plus dexmedetomidine showed less perineural inflammation at 24 h than the bupivacaine group when compared with the saline control.     

外周阻滞对炎症导致的大鼠前列腺素E2和环氧合酶表达的影响

背景外周炎性疼痛与脊髓COX-2（环氧合酶-2）上调及随之而来的中枢前列腺素E2（PGE2）水平升高和痛觉超敏的发生有关。本研究中,我们评估了布比卡因经神经阻滞和全身应用对PGE2和COX在外周炎症大鼠模型脊髓表达的影响。方法所有大鼠随机接受3种注射：①左后爪皮下注射（0．2ml2％w／v角又聚糖或盐水）,②左坐骨神经阻滞（0．2ml0．5％布比卡因或盐水）,③全身注射（肩胛间皮下0．2ml0．5％布比卡因或盐水）。测量局部水肿、发热、机械性痛觉超敏、脑脊液PGE2浓度和脊髓背根神经节COX-1、COX-2表达。结果证实布比卡因阻滞可以自0弱炎性疼痛模型的痛觉超敏和局部炎症,这一效果可能与抑制外周炎症导致脊髓和背根神经节的COX-2表达增强有关。脑脊液PGE2的生成也被削弱。全身应用布比卡因没有减轻痛觉超敏和局部炎症或COX表达。结论本研究结果强烈提示,局部麻醉药全身用药或神经阻滞,是在不同水平起作用的。     

Decreased incidence of tourniquet pain during spinal anesthesia with bupivacaine. A possible explanation

In a previous report, the incidence of tourniquet pain was found to be 25% with bupivacaine and 60% with tetracaine (P less than 0.05) spinal anesthesia. On the other hand, tetracaine is more potent than bupivacaine in abolishing the single-compound action potential in vitro in isolated nerves. These conflicting observations may be reconciled if bupivacaine produced greater frequency-dependent conduction blockade of nerve action potentials. This hypothesis was tested in C fibers of isolated, desheathed rabbit vagus nerves. The nerves were supramaximally stimulated at frequencies of 9 or 15 Hz. After a control period, the nerves were exposed to bupivacaine (0.2 mM) or tetracaine (0.02 mM) for 30 minutes. The local anesthetics were then washed out by continuous constant-rate perfusion. The decline and recovery of the first and last action potential amplitudes of the train were measured. Bupivacaine and tetracaine produced similar depression of the first action potential of the 9-Hz and 15-Hz trains. However, bupivacaine caused a delayed recovery of the last action potential of the 15-Hz train but not of the 9-Hz train. These results show that bupivacaine produces greater frequency-dependent conduction blockade of C fibers than does tetracaine. These findings offer a possible explanation as to why spinal anesthesia with bupivacaine results in a lower incidence of tourniquet pain than tetracaine.     

Combined lumbar and sacral plexus block compared with plain bupivacaine spinal anesthesia for hip fractures in the elderly

BACKGROUND AND OBJECTIVES: This prospective randomized study was designed to determine the hemodynamic effects and quality of combined lumbar and sacral plexus block compared with plain bupivacaine spinal anesthesia in the elderly for repair of proximal femoral fractures. METHODS: Twenty-nine elderly patients ranging in age from 68 to 97 years were randomly assigned to 2 groups: a spinal anesthesia group with single-shot 3 mL 0.5% plain bupivacaine, and a combined block group with 30 mL lidocaine 1.33% with epinephrine for the posterior lumbar plexus block and 10 mL same mixture for the parasacral block and an iliac crest block with 5 mL lidocaine 1%. RESULTS: No need for general anesthesia was encountered in either group. Anesthesia was judged unsatisfactory in 1 of 15 patients in the combined block group. The initial decrease of mean arterial pressure was 38% in the spinal group and 27% in the block group and was not significantly different. A more prolonged hemodynamic effect was found in the spinal group, indicated by the more frequent use of ephedrine to stabilize blood pressure (P<.05). Patients over 85 years had a significantly larger decrease in blood pressure than younger patients (P<.01). CONCLUSIONS: Plain bupivacaine spinal anesthesia and combined lumbar/sacral plexus block provided adequate anesthesia for repair of hip fracture in the elderly. Hypotension was induced by both the combined peripheral nerve block and plain bupivacaine spinal anesthesia in aged patients; hypotension was found to be longer lasting after spinal anesthesia and of a larger magnitude in patients over 85 years of age.     

Arterial and venous plasma levels of bupivacaine following peripheral nerve blocks.

Mean arterial plasma (MAP) and peripheral mean venous plasma (MVP) levels of bupivacaine were ascertained in 3 groups of 10 patients each for: (1) intercostal nerve block, 400 mg; (2) block of the sciatic, femoral, and lateral femoral cutaneous nerves, with or without block of the obturator nerve, 400 mg; and (3) supraclavicular brachial plexus block, 300 mg. MAP levels were consistently higher than simultaneously sampled MVP levels, the highest levels occurring from bilateral intercostal nerve block. No evidence of systemic toxicity was observed. The results suggest that bupivacaine has a much wider margin of safety in humans than is now stated.     

Reduction of experimental neuroma formation with ricin.

Twenty rat sciatic nerves were bilaterally transected, one as control, and one intraneurally injected with ricin. At 11 weeks, all controls demonstrated large neuromas. Ten injected nerves had no neuroma or a significantly smaller one, while the other 10 had neuroma formation similar to controls. No effect on distant dorsal root ganglia or spinal cord was seen. Thirteen additional rats underwent nerve injection with I125-labeled ricin. At one week, most radioactivity was localized to sciatic nerve, surrounding muscle, and thyroid, with trace amounts in dorsal root ganglia and spinal cord. Intraneural ricin can inhibit neuroma formation in transected nerve, but results in unpredictable uptake of ricin by nerve and excess spillage into surrounding tissues.     

PREDICTION OF THE SPREAD OF REPEATED SPINAL ANAESTHESIA WITH BUPIVACAINE

We have studied in 56 patients the predictability of spreadof repeated spinal anaesthesia in the same patient on the basisof a previous block. With plain 0.5% bupivacaine, predictionof the second block was accurate. A significantly higher orlower spread of analgesia than in the previous block was achievedwhen plain 0.5% bupivacaine was administered using a modifiedtechnique7mdash;sitting position or lower interspace, respectively.When hyperbaric 0.5% bupivacaine was injected instead of plainsolution for the second block using a similar technique, nobaricity-related correlation was found between the first andsecond blocks. Change in technique did not reduce interindividualvariation in the spread of analgesia. We conclude that individualanatomical properties may play a more important role than, forexample, baricity in subarachnoid distribution of a local anaestheticsolution.     

Low-dose bupivacaine-fentanyl spinal anesthesia for cesarean delivery

BACKGROUND AND OBJECTIVES: The hypotension following spinal anesthesia remains commonplace in cesarean delivery. Intrathecal opioids are synergistic with local anesthetics and intensify sensory block without increasing sympathetic block. The combination makes it possible to achieve spinal anesthesia with otherwise inadequate doses of local anesthetic. We hypothesized that this phenomenon could be used to provide spinal anesthesia for cesarean delivery while incurring less frequent hypotension. METHODS: Thirty-two women scheduled for cesarean delivery were divided into 2 groups of patients who received a spinal injection of either 10 mg of isobaric (plain) bupivacaine 0.5% or 5 mg of isobaric bupivacaine with 25 microg fentanyl added. Each measurement of a systolic blood pressure less than 95 mm Hg or a decrease in systolic pressure of greater than 25% from baseline was considered as hypotension and treated with a bolus of 5 to 10 mg of intravenous ephedrine. RESULTS: Spinal block provided surgical anesthesia in all patients. Peak sensory level was higher (T3 v T4. 5) and motor block more intense in the plain bupivacaine group. The plain bupivacaine patients were more likely to require treatment for hypotension (94% v 31%) and had more persistent hypotension (4.8 v 0.6 hypotensive measurements per patient) than patients in the minidose bupivacaine-fentanyl group. Mean ephedrine requirements were 23.8 mg and 2.8 mg, respectively, for the 2 groups. Patients in the plain bupivacaine group also complained of nausea more frequently than patients in the minidose bupivacaine-fentanyl group (69% v 31%). CONCLUSIONS: Bupivacaine 5 mg + fentanyl 25 microg provided spinal anesthesia for cesarean delivery with less hypotension, vasopressor requirements, and nausea than spinal anesthesia with 10 mg bupivacaine.     

Methylprednisolone shortens the effects of bupivacaine on sensory nerve fibers in vivo

Perineural administration of corticosteroids is frequently applied in the treatment of a variety of chronic pain conditions. Methylprednisolone selectively inhibits the transmission of nerve impulses in C-fibers whereas A-fiber activity is unaffected.
In the present study the effect of a mixture of 0.05 ml of methyprednisolone (40 mg/ml) and 0.05 ml of bupivacaine (5 mg/ml) was compared to that of 0.05 ml bupivacaine (5 mg/ml) using a plantar nerve block model in the rat. The conduction of impulses in electrically stimulated A-fibers of the plantar nerve was monitored by a bipolar volley recording from the sciatic nerve. Impulse conduction in electrically stimulated C-fibers was studied through a C-fiber evoked segmental flexion reflex.
The function of both the A-fibers and the C-fibers exposed to the methylprednisolone-bupivacaine mixture showed a less profound block with signs of earlier recovery than those exposed to plain bupivacaine. The A-fibers recovered somewhat faster than the C-fibers.
It is postulated that methylprednisolone adjuvant to bupivacaine affects the intra-axonal uptake of bupivacaine in C-fibers but not in A-fibers by some unknown mechanism. The effect seems to be longer lasting in C-fibers than in A-fibers.     

Intrathecal plainvs hyperbaric bupivacaine for labour analgesia: efficacy and side effects

Purpose

Baricity is an important determinant of block characteristics of the spinal component of a combined spinal epidural (CSE) for labour analgesia. This study compares the analgesic efficacy and side effects of intrathecally administered plain and hyperbaric bupivacaine (both with fentanyl) during active labour.

Methods

Sixty-two women in active labour (cervical dilatation >- 5 cm and pain score > 5) were randomized in a prospective, single-blinded fashion to receive 2.5 mg of either hyperbaric or plain bupivacaine both combined with 15 μg of fentanyl as the spinal component of a CSE. The primary outcome was failure of satisfactory analgesia within ten minutes of the intrathecal injection as defined by a verbal pain score > 3. Secondary outcomes included need for rescue analgesia, hypotension, respiratory depression, nausea and vomiting, pruritus and sustained fetal bradycardia.

Results

Sixty patients were analyzed. The failure rates were 20% in the hyperbaric groupvs 0% in the plain group (P = 0.024). The plain solution provided faster onset, higher sensory levels and less motor block at all times during the first 30 min. The incidence of both pruritus and sustained fetal bradycardia was 33% in the plain group and 10% in the hyperbaric group (P = 0.03).

Conclusion

A plain rather than hyperbaric solution of bupivacaine 2.5 mg with fentanyl 15 μg provides a faster onset of analgesia, higher sensory levels and less motor block, while demonstrating an increased incidence of pruritus and sustained fetal bradycardia.     

The effect of baricity of intrathecal bupivacaine for elective cesarean delivery on maternal cardiac output: a randomized study

BackgroundHemodynamic instability during spinal anesthesia for cesarean delivery is associated with adverse maternal and fetal outcomes. Plain and hyperbaric bupivacaine are commonly used for cesarean delivery, however, their distinctive pharmacologic properties may affect maternal hemodynamic profiles differently. The aim of this study was to compare hemodynamic profiles using a suprasternal Doppler cardiac output (CO) monitor in healthy term parturients randomized to receive plain or hyperbaric bupivacaine for cesarean delivery.MethodsOne hundred-and-sixty-eight healthy parturients scheduled for elective cesarean delivery were randomly assigned to receive 10.9 mg of intrathecal 0.5% plain or hyperbaric bupivacaine, both with 0.2 mg morphine. The primary outcome was CO change after spinal anesthesia. Secondary outcomes were the incidence of hypotension, vasopressor use, and conversion to general anesthesia.ResultsThe mean (±SD) CO at baseline, 1 min and 5 min after spinal anesthesia, and after placental delivery was 4.6 ± 1.2, 5.4 ± 1.3, 5.1 ± 1.4, and 6.4 ± 1.7 L/min in the plain bupivacaine, and 4.5 ± 1.1, 5.2 ± 1.3, 4.9 ± 1.3, and 6.2 ± 1.9 L/min in the hyperbaric bupivacaine group. There were no significant differences in CO, mean arterial pressure, or systemic vascular resistance. Incidences of hypotension, vasopressor and supplemental analgesic use, and conversion to general anesthesia, were not different between groups.ConclusionsCardiac output changes after plain or hyperbaric bupivacaine were not different in term parturients undergoing spinal anesthesia for cesarean delivery. Further studies comparing block quality and the rate of conversion to general anesthesia are required.     

The effect of a priming epidural injection of adrenaline on epidural blockade with bupivacaine

Twenty-four patients receiving epidural anaesthesia were studied to test the hypothesis that 1:200,000 adrenaline administered into the epidural space 5 minutes before 20 ml bupivacaine 0.5% would improve nerve block and delay systemic absorption of the local anaesthetic. Group A/B received 20 ml adrenaline 1:200,000 5 minutes before 20 ml bupivacaine 0.5%, group S/BA 20 ml saline followed by 20 ml bupivacaine 0.5% with 100 micrograms adrenaline, and group S/B saline 20 ml followed by 20 ml plain bupivacaine 0.5%. Mean maximum plasma concentrations of bupivacaine tended to be lower in the adrenaline groups. A delay in the time to peak plasma concentration of bupivacaine was noted in the A/B group; this indicated that priming with adrenaline may be effective at delaying early systemic uptake of the local anaesthetic. In both adrenaline groups a more prolonged epidural block and increased efficacy were noted, although this was only significant for the duration of block at T6 (p = 0.023) and duration of motor block at Bromage level 1 (p = 0.016) in group A/B. There seems little clinical advantage in administering adrenaline 5 minutes before bupivacaine.