Epidural test dose with levobupivacaine and ropivacaine: determination of ED(50) motor block after spinal administration

Background. When a test is required to detect a possible intrathecalcatheter, many would seek to use the same local anaestheticas that used for epidural analgesia. The rapid onset of inappropriatemotor block after a local anaesthetic administered epidurallyimplies intrathecal spread. Because of claims of greater sensory–motorseparation, or because of reduced potency compared with bupivacaine,the efficacy of the new local anaesthetics in intrathecal testinghas been questioned. The aim of this study was to establishthe feasibility of a test dose for an inadvertent intrathecalcatheter using ropivacaine and levobupivacaine, and to establishthe dose required. Methods. Sixty women undergoing elective Caesarean section witha combined spinal– epidural technique were enrolled intothis prospective, double-blind sequential allocation study.The women were randomized to receive plain levobupivacaine 0.5%or ropivacaine 0.5% intrathecally. The dose was determined accordingto up–down sequential allocation. The end-point was anyevidence of lower limb motor block within 5 min of injection. Results. The ED₅₀ motor block at 5 min was 4.8 mg (95% CI, 4.49,5.28) for levobupivacaine and 5.9 mg (95% CI, 4.82, 6.98) forropivacaine (95% CI difference, 0.052, 1.98) (P=0.04). The estimatedED₉₅ motor block was 5.9 mg (95% CI 5.19, 6.71) for levobupivacaineand 8.3 mg (95% CI, 6.30, 10.44) for ropivacaine. The potencyratio between the two drugs was 0.83 (95% CI, 0.69, 0.99). Conclusions. Both local anaesthetics produce evidence of motorblock within 5 min of intrathecal injection and could serveas tests of intrathecal administration. Derived ED₉₅ valuessuggest 10 mg doses should be effective, but this study didnot measure predictive value. Ropivacaine is less potent formotor block than levobupivacaine by a factor of 0.83 (P<0.04). Br J Anaesth 2004; 92: 850–3     

Density of spinal anaesthetic solutions of bupivacaine, levobupivacaine, and ropivacaine with and without dextrose

Background. Spread of intrathecal local anaesthetics is determinedprincipally by baricity and position of the patient. Hypobaricsolutions of bupivacaine are characterized by an unpredictablespread of sensory block whereas addition of dextrose 80 mg ml^–1provides a predictable spread but to high thoracic levels. Incontrast, dextrose concentrations between 8 and 30 mg ml^–1have shown reliable and consistent spread for surgery. Hence,the aim of this study was to determine the density of bupivacaine,levobupivacaine, and ropivacaine with and without dextrose atboth 23 and 37°C before embarking on clinical studies. Methods. Density (mg ml^–1) was measured using the methodof mechanical oscillation resonance, accurate to five decimalplaces on 1250 samples. 500 density measurements were performedin a randomized, blind fashion at 23 and 37°C on 10 plainsolutions of bupivacaine (2.5, 5, and 7.5 mg ml^–1) levobupivacaine(2.5, 5, and 7.5 mg ml^–1) and ropivacaine (2, 5, 7.5,and 10 mg ml^–1). Following this, 750 density measurementswere taken at 23 and 37°C on the 5 mg ml^–1 solutionsof bupivacaine, levobupivacaine, and ropivacaine with addeddextrose (10, 20, 30, 50, and 80 mg ml^–1). Results. There was a linear relationship between density anddextrose concentration for all three local anaesthetics (R²=0.99)at 23 and 37°C. The mean density of levobupivacaine 5 mgml^–1 was significantly greater than the densities of bupivacaine5 mg ml^–1 and ropivacaine 5 mg ml^–1 after adjustingfor dextrose concentration using analysis of covariance. Thisdifference existed both at 23 and 37°C. The mean (SD) densityof levobupivacaine 7.5 mg ml^–1 was 1.00056 (0.00003) mgml^–1, the lower 0.5% percentile (1.00047 mg ml^–1)lying above the upper limit of hypobaricity for all patientgroups. Conclusions. The density of local anaesthetics decreases withincreasing temperature and increases in a linear fashion withthe addition of dextrose. Levobupivacaine 5 mg ml^–1 hasa significantly higher density compared with bupivacaine 5 mgml^–1 and ropivacaine 5 mg ml^–1 at 23 and 37°Cboth with and without dextrose. Levobupivacaine 7.5 mg ml^–1is an isobaric solution within all patient groups at 37°C. Br J Anaesth 2004; 92: 547–51     

Long-term evaluation of motor function following intraneural injection of ropivacaine using walking track analysis in rats

Background. There is a paucity of data regarding neurologicfunction following nerve injury. Our objective was the long-termevaluation of motor function following intraneural injectionof ropivacaine in rats using the sciatic function index (SFI),derived from walking track analysis. Methods. Rats were randomly assigned to one of four groups of13 animals each. A needle was inserted under magnification intothe left sciatic nerve and 0.2 ml of normal saline, formalin15%, ropivacaine 0.2 or 0.75% were injected intraneurally. Theright side was sham operated. Walking track analysis was performedthe day before and on days 1, 4, 7, 11, 15, 18, 21, and 67 followingintraneural injection. At the end of the experiment (day 67)a semi-quantitative evaluation of neuropathologic changes wasperformed by three independent observers. Results. Animals treated with saline and ropivacaine (0.2 and0.75%) had no detectable impairment of motor function at anytime point. In contrast, rats treated with formalin had a completeloss of motor function immediately after the intraneural injection,which persisted until day 21 and returned to normal by day 67.Important histopathologic changes (score=2) with excellent inter-observeragreement were seen only in the group treated with formalin.This applied to both axonal degeneration and Schwann cell densityevaluations. Conclusions. These findings suggest that intraneural injectionsof ropivacaine at concentrations routinely used in clinicalpractice appear to have no deleterious effect on sciatic nervemotor function in this experimental rat model.     

High-dose bupivacaine, levobupivacaine and ropivacaine in axillary brachial plexus block

BACKGROUND: Racemic bupivacaine is clinically similar to levobupivacaine, or ropivacaine. The drugs were compared in brachial plexus block for the first time in the same randomized and double-blind study. METHODS: In 90 patients scheduled for hand and forearm surgery, a perivascular axillary brachial plexus block was performed with 45 ml of 5 mg ml(-1) of either racemic bupivacaine-HCl, levobupivacaine-HCl, or ropivacaine-HCl. Sensory (cold) and motor (hand clasp, and movement of elbow) block were scored, and the patient was interviewed in the postoperative evening and the following morning. Time to normal function of the arm was registered. RESULTS: After similar onsets of sensory block, the sum of completely anaesthetized innervation areas of the four main nerves at 45 min was greater in the ropivacaine group than in the levobupivacaine group (P < 0.01). Simultaneously, complete motor block at the elbow was more frequent in the ropivacaine group (67%) than in the bupivacaine (47%) and levobupivacaine groups (30%) (P < 0.01). In the hand, the corresponding results were 83%, 77%, and 57%, respectively (NS). Two patients in the levobupivacaine and one in the ropivacaine group needed general anaesthesia. Mean duration of the blocks was similar in the bupivacaine, levobupivacaine and ropivacaine groups at 19.3 h, 19.5 h, and 17.3 h, respectively (NS). Two patients were dissatisfied with the long block duration. CONCLUSION: Ropivacaine-HCl 5 mg ml(-1) produced slightly better sensory and motor block intensity than the same dose of levobupivacaine-HCl. General success in relation to surgery and in the duration of the blocks was similar in the three groups.     

Double-blind comparison of ropivacaine 7.5 mg ml(-1) with bupivacaine 5 mg ml(-1) for sciatic nerve block

Two groups of 12 patients had a sciatic nerve block performedwith 20 ml of either ropivacaine 7.5 mg ml^–1 or bupivacaine5 mg ml^–1. There was no statistically significant differencein the mean time to onset of complete anaesthesia of the footor to first request for post-operative analgesia. The qualityof the block was the same in each group. Although there wasno statistically significant difference in the mean time topeak plasma concentrations the mean peak concentration of ropivacainewas significantly higher than that of bupivacaine. There wereno signs of systemic local anaesthetic toxicity in any patientin either group. Br J Anaesth 2001; 86: 674–7     

Systemic toxic effects of local anaesthetics

Local anaesthetics are widely used in the provision of local/regional anaesthesia and the management of acute and chronic pain. Their mechanism of action temporarily inhibits voltage gated sodium channels in neuronal plasma membranes. Local anaesthetic systemic toxicity (LAST) is a serious yet largely preventable complication that can occur by any of the multiple routes of administration. LAST predominantly affects the central nervous and cardiovascular systems. Awareness of LAST and vigilance during administration of local anaesthetics may help in early recognition and successful management of the toxicity. Intralipid emulsion (ILE) infusions have been successfully used in reversing local anaesthetic-induced cardiotoxicity. Since 2007 in the UK, ILE infusion has been incorporated into the safety guidelines for management of LAST.     

Systemic toxic effects of local anaesthetics

Local anaesthetics are widely used in the provision of local/regional anaesthesia and the management of acute and chronic pain. Their mechanism of action temporarily inhibits voltage gated sodium channels in neuronal plasma membranes. Local anaesthetic systemic toxicity (LAST) is a serious yet largely preventable complication that can occur by any of the multiple routes of administration. LAST predominantly affects the central nervous and cardiovascular systems. Awareness of LAST and vigilance during administration of local anaesthetics may help in early recognition and successful management of the toxicity. Intralipid emulsion (ILE) infusions have been successfully used in reversing local anaesthetic-induced cardiotoxicity. Since 2007 in the UK, ILE infusion has been incorporated into the safety guidelines for management of LAST.     

Plasma levobupivacaine concentrations following scalp block in patients undergoing awake craniotomy

Background. Levobupivacaine is an effective local anaestheticagent for nerve blockade with less systemic toxicity than racemicbupivacaine. The safety and efficacy of levobupivacaine forscalp blockade during awake craniotomy have not been addressedpreviously. Methods. Serial arterial plasma levobupivacaine concentrationsfollowing scalp blockade were measured to 2 h in 10 patientsbooked for awake craniotomy for epilepsy or tumour surgery.Bilateral scalp blockade providing surgical anaesthesia wasachieved with a mean dose of 177 mg (2.5 mg kg^–1, range1.6–3.2 mg kg^–1) of levobupivacaine (0.5%, 5 mgml^–1) with epinephrine (5 µg ml^–1) added immediatelybefore the block insertion. Results. The maximum measured plasma levobupivacaine concentrationwas 1.58 (0.44) µg ml^–1 [mean (SD)] with a meantime to peak plasma concentration of 12 (4) min. There wereno episodes in any of the 10 patients of symptoms or signs suggestiveof either CNS or CVS toxicity. Conclusions. This study demonstrated a relatively rapid riseof plasma levobupivacaine concentration without evidence ofcardiovascular or central nervous system sequelae in a samplepopulation of patients who may be particularly prone to perioperativeseizures.     

The duration of action of bupivacaine, levobupivacaine, ropivacaine and pethidine in peripheral nerve block in the rat

Background : There is a current interest in local anaesthetic drugs/formulations exhibiting long durations of sensory block and minor motor–blocking effects.
Objectives : To compare the duration of sensory and motor blockade in peripheral nerve blocks induced by the new agents ropivacaine and levobupivacaine, with that of racemic bupivacaine and pethidine.
Methods : Groups of 8 male Sprague–Dawley rats were subjected to infraorbital (IONB) or sciatic nerve block (SNB) employing 0.2 ml of differently concentrated solutions of bupivacaine, levobupivacaine, ropivacaine or pethidine. The sensory blocking effect in IONB is expressed as (i) the time to elicitation of an abdominal jerk by electrical stimulation at arbitrarily chosen (threshold) intensities (IONB degree 3, 5, 8 and 10), and as (ii) the area under the curve (AUC, threshold intensities vs time). The duration of motor block in SNB is given as the time from injection to regained ability to walk and grip normally with the toes. Comparisons of the dose–effect relationships for the investigated agents were made by analysis of covariance.
Results : In IONB the log (dose)–log (effect) lines for bupivacaine, levobupivacaine and ropivacaine did not deviate from parallelism. The duration of sensory block induced by equimolar doses of these agents was similar, although bupivacaine exerted more pronounced effects than levobupivacaine (AUC by 25%, P=0.001; IONB degree 3 by 14%, P=0.03). In SNB only the log (dose)–log (duration) lines for bupivacaine vs levobupivacaine were found not to deviate from parallelism, both agents exerting similar durations of action. The motor–blocking effects of ropivacaine showed an inverse dose–duration relationship (P=0.019).
Conclusions : Equimolar doses of the investigated local anaesthetics exerted similar durations of sensory blockade in a peripheral nerve block model in the rat.     

Contralateral effect of amitriptyline and bupivacaine for sciatic nerve block in an animal model of inflammation

Background. Using a carrageenan inflammation rat model, we evaluatedtwo experimental approaches to prolong sciatic nerve block oncontralateral hyperalgesia. Method. We performed ipsilateral sciatic nerve block on theinflamed hind paw with bupivacaine-loaded microspheres suspendedin dexamethasone (bupivacaine 12.5 mg) and with amitriptyline(6.25 and 12.5 mg) as ultralong-acting local anaesthetics. Bupivacaine(1.25 mg) was used as long-acting local anaesthetic and salinewas used as a control. The sixth group received amitriptyline6.25 mg intraperitoneally (n=10 for each group). Results. The duration of ipsilateral nerve block was 2 h forbupivacaine, 7 h for amitriptyline 6.25 mg, 11 h for amitriptyline12.5 mg and 21 h for bupivacaine-loaded microspheres in suspensionwith dexamethasone. Whereas contralateral hyperalgesia was notobserved during block produced by bupivacaine-loaded microspheres,contralateral hyperalgesia was observed with sciatic nerve blockusing amitriptyline. Conclusions. Because of the differential effect observed onthe contralateral side, the mechanism underlying the prolongationof ipsilateral block with amitriptyline may not result onlyfrom a prolonged Na⁺ channel blockade but might be explainedby a local toxic effect or lack of systemic actions.     

Grand mal convulsion and plasma concentrations after intravascular injection of ropivacaine for axillary brachial plexus blockade

We report a patient to whom ropivacaine 1.1 mg kg^–1was administered for brachial plexus blockade and who developedgrand mal convulsions because of inadvertent i.v. injection.No symptoms of cardiovascular toxicity occurred. Venous bloodsamples were taken 15, 45, 75 and 155 min after the injection.The measured total plasma concentrations of ropivacaine were3.3, 1.6, 1.2 and 1.0 mg litre^–1 respectively.Initial plasma concentration after the end of the injectionperiod was estimated at 5.75 mg litre^–1 usinga two-compartment pharmacokinetic model. Br J Anaesth 2001; 87: 784–7     

Effects of ultrasound guidance on the minimum effective anaesthetic volume required to block the femoral nerve

Background: We tested the hypothesis that ultrasound guidance may reducethe minimum effective anaesthetic volume (MEAV₅₀) of ropivacaine0.5% required to block the femoral nerve compared with nervestimulation guidance. Methods: After standard premedication and sciatic nerve block were given,60 patients undergoing knee arthroscopy were randomly allocatedto receive a femoral nerve block with ropivacaine 0.5% usingeither nerve stimulation (group NS, n = 30) or ultrasound (groupUS, n = 30) guidance. The volume of the injected solution wasvaried for consecutive patients based on an up-and-down staircasemethod according to the response of the previous patient. Theinitial volume was 12 ml. A double-blinded observer evaluatedthe occurrence of complete loss of pinprick sensation in thefemoral nerve distribution, with concomitant block of the quadricepsmuscle: positive or negative responses within 30 min after theinjection determined a 3 ml decrease or increase for the nextpatient, respectively. Results: The mean (SD) MEAV₅₀ for femoral nerve block was 15 (4) ml (95%CI, 7–23 ml) in group US and 26 (4) ml (95% CI, 19–33ml) in group NS (P = 0.002). The effective dose in 95% of cases(ED₉₅) calculated with probit transformation and logistic regressionanalysis was 22 ml (95% CI, 13–36 ml) in group US, and41 ml (95% CI, fs 24–66 ml) in group NS. Conclusions: Ultrasound guidance provided a 42% reduction in the MEAV ofropivacaine 0.5% required to block the femoral nerve as comparedwith the nerve stimulation guidance.     

Effects of hypoxia and isoflurane on liver blood flow: the role of adenosine

We investigated the role of endogenous adenosine in mediatingthe effects of hypoxia and isoflurane on portal tributary bloodflow (PTBF) and hepatic arterial blood flow (HABF) in rats.Liver blood flows were determined using radiolabelled microspheres.Hypoxia resulting from the exposure of rats to an atmospherecontaining 15% oxygen for 30 min decreased PTBF (23%) (P<0.05)and cardiac index (15%) (P<0.05), and increased HABF (78%)(P<0.05). Isoflurane (1.4 vol%) increased HABF in both normoxicand hypoxic conditions but did not affect PTBF. The adenosinereceptor antagonist 8-phenyltheophylline attenuated the hypoxia-inducedincrease in HABF but did not affect that resulting from theadministration of isoflurane. In conclusion, in contrast tothe increase in HABF induced by hypoxia, that induced by isofluraneappears to be independent of endogenous adenosine. Br J Anaesth 2000; 86: 425–7     

Lidocaine reduces ischaemic but not reperfusion injury in isolated rat heart

The local anaesthetic lidocaine protects the myocardium in ischaemia–reperfusionsituations. It is not known if this is the consequence of ananti-ischaemic effect or an effect on reperfusion injury. Therefore,we investigated the effect of two concentrations of lidocaineon myocardial ischaemia–reperfusion injury and on reperfusioninjury alone. We used an isolated rat heart model where heartrate, ventricular volume and coronary flow were kept constant.Hearts underwent 45 min of low-flow ischaemia followed by 90min reperfusion. Two groups received lidocaine 1.7 or 17 µgml^–1 starting 5 min before the onset of reperfusion. Intwo additional groups, lidocaine infusion started 5 min beforelow-flow ischaemia. In all groups, lidocaine administrationwas stopped after 15 min of reperfusion. One group served asan untreated control (n=11 in each group). Left ventriculardeveloped pressure (LVDP) and total creatine kinase release(CKR) were measured. Lidocaine administration during ischaemiaand reperfusion led to an improved recovery of LVDP during reperfusion(1.7 µg ml^–1, 54 (SEM 10) mm Hg; 17 µg ml^–1,71 (9) mm Hg at 30 min of reperfusion; both significantly differentfrom control (21 (4) mm Hg) (P<0.05)) and a reduced CKR (1.7µg ml^–1, 79 (13) IU; 17 µg ml^–1, 52(8) IU at 30 min of reperfusion; both significantly differentfrom control (130 (8) IU (P<0.05)). Lidocaine given duringearly reperfusion only, affected neither LVDP during reperfusion(1.7 µg ml^–1, 19 (6) mm Hg (P=1.0); 17 µgml^–1, 36 (8) mm Hg (P=0.46)) nor CKR (156 (21) IU (P=0.50)and 106 (14) IU (P=0.57)). We conclude that lidocaine protectsthe myocardium against ischaemic but not against reperfusioninjury in the isolated rat heart. Br J Anaesth 2001; 86: 846–52     

Effect of lidocaine on ischaemic preconditioning in isolated rat heart

Background. Lidocaine is frequently used as an agent to treatventricular arrhythmias associated with acute myocardial ischaemia.Lidocaine is a potent blocker not only of sodium channels, butalso of ATP-sensitive potassium channels. The opening of thesechannels is a key mechanism of ischaemic preconditioning. Weinvestigated the hypothesis that lidocaine blocks the cardioprotectioninduced by ischaemic preconditioning. Methods. Isolated rat hearts (n=60) were subjected to 30 minof no-flow ischaemia and 60 min of reperfusion. Control hearts(CON) underwent no further intervention. Preconditioned hearts(PC) received two 5-min periods of ischaemia separated by 10min of reflow before the 30 min ischaemia. In three groups,lidocaine was infused at concentrations of 2, 10 or 20 µgml^–1 for 5 min before the preconditioning ischaemia. Leftventricular developed pressure (LVDP) and infarct size (IS)(triphenyltetrazolium choride staining) were measured as variablesof ventricular function and cellular injury, respectively. Results. PC reduced IS from 24.8 (SEM 4.1) % to 4.0 (0.7) %of the area at risk (P<0.05). Adding 2 or 10 µg ml^–1lidocaine had no effect on IS compared with PC alone (3.7 (0.7)%, 6.9 (1.8) %). Adding 20 µg ml^–1 lidocaine increasedIS to 14.1 (2.5) % compared with PC (P<0.05). Baseline LVDPwas similar in all groups (111.4 (2.1) mm Hg). Compared withCON, PC improved functional recovery (after 60 min of reperfusion;52.3 (5.9) mm Hg vs 16.0 (4.0) mm Hg, P<0.01). The improvedventricular function was not influenced by addition of 2 or10 µg ml^–1 lidocaine (47.3 (5.7) mm Hg, not significant;45.3 (7.3) mm Hg, not significant), but was blocked by the infusionof 20 µg ml^–1 lidocaine (22.5 (8.0) mm Hg, P<0.01vs PC). Conclusions. Lidocaine blocks the cardioprotection induced byischaemic preconditioning only at supratherapeutic concentrations.     

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.     

Efficacy and uptake of ropivacaine and bupivacaine after single intra-articular injection in the knee joint

The efficacy of ropivacaine 100 mg (5 mg ml^–1),150 mg (7.5 mg ml^–1) and 200 mg (10 mg ml^–1)and bupivacaine 100 mg (5 mg ml^–1) givenby intra-articular injection into the knee after the end ofsurgery was studied in 72 ASA I–II patients scheduledfor elective knee arthroscopy under general anaesthesia in arandomized, double-blind study. Kapake (paracetamol 1 gand codeine 60 mg) was given as a supplementary analgesic.Pain scores were assessed 1–4 h after surgery and a verbalrating scale of overall pain severity was assessed on secondpostoperative day. Ropivacaine or bupivacaine concentrationswere determined in peripheral venous plasma up to 3 h afterinjection in eight patients in each group. Verbal rating painscores were lower with ropivacaine 150 mg compared withbupivacaine 100 mg (P<0.05). There was a tendency forlower analgesic consumption and pain scores with all doses ofropivacaine (not significant). The mean (SD) maximum total plasmaconcentrations of ropivacaine were 0.64 (0.25), 0.78 (0.43),and 1.29 (0.46) mg litre^–1 after 100, 150 and200 mg. The corresponding unbound concentrations were 0.018(0.009), 0.024 (0.020) and 0.047 (0.022) mg litre^–1.Both were proportional to the dose. The maximum total concentrationafter bupivacaine 100 mg was 0.57 (0.36) mg litre^–1.The time to reach maximum plasma concentration was similar forall doses and varied between 20 and 180 min. All concentrationswere well below the threshold for systemic toxicity. Br J Anaesth 2001; 87: 570–6     

Comparison of ropivacaine 0.5% (in glucose 5%) with bupivacaine 0.5% (in glucose 8%) for spinal anaesthesia for elective surgery

Background. Hyperbaric solutions of ropivacaine have been usedsuccessfully to provide spinal anaesthesia. This study was designedto compare the clinical efficacy of hyperbaric ropivacaine withthat of the commercially available hyperbaric preparation ofbupivacaine. Methods. Forty ASA grade I–II patients undergoing lower-abdominal,perineal or lower-limb surgery under spinal anaesthesia wererecruited and randomized to receive ropivacaine 5 mg ml^–1(with glucose 50 mg ml^–1), 3 ml or bupivacaine 5 mg ml^–1(with glucose 80 mg ml^–1), 3 ml. The level and durationof sensory block, intensity and duration of motor block, andtime to mobilize and micturate were recorded. Patients wereinterviewed at 24 h and at 1 week to identify any residual problems. Results. All blocks were adequate for the proposed surgery,but there were significant differences between the two groupsin mean time to onset of sensory block at T10 (ropivacaine 5min; bupivacaine 2 min; P<0.005), median maximum extent (ropivacaineT7; bupivacaine T5; P<0.005) and mean duration of sensoryblock at T10 (ropivacaine 56.5 min; bupivacaine 118 min; P=0.001).Patients receiving ropivacaine mobilized sooner (ropivacainemean 253.5 min; bupivacaine 331 min; P=0.002) and passed urinesooner (ropivacaine mean 276 min; bupivacaine 340.5 min; P=0.01)than those receiving bupivacaine. More patients in the bupivacainegroup required treatment for hypotension (>30% decrease insystolic pressure; P=0.001). Conclusions. Ropivacaine 15 mg in glucose 50 mg ml^–1 providesreliable spinal anaesthesia of shorter duration and with lesshypotension than bupivacaine. The recovery profile for ropivacainemay be of interest given that more surgery is being performedin the day-case setting. Br J Anaesth 2003; 90: 304–8     

Cardiotoxicity of ropivacaine – a new amide local anaesthetic agent

Anaesthetically equipotent doses of lidocaine, bupivacaine and a new bupivacaine-like local anaesthetic agent, ropivacaine, were injected into the left anterior descending coronary artery of pentobarbital-anaesthetized pigs. The aim was to study the cardiotoxicity of ropivacaine in relation to the two other drugs. A random, crossover, dose response study design was used. The following doses of the drugs were administered: lidocaine (L): 1,2,4,8 and 16 mg, bupivacaine (B): 0.25, 0.5, 1,2 and 4 mg and ropivacaine (R): 0.33, 0.66 1.33, 2.66 and 5.33 mg. Systemic haemodynamics, left ventricular dP/dT and a 12-lead electrocardiogram were recorded continuously during the study period. The drugs depressed cardiac contractility in relation to their local anaesthetic potency on the isolated nerve-4:3:1 (B:R:L). The prolongation of the ECG QRS-interval was regarded as a measure of electrophysiologic toxicity. Comparable prolongation of the QRS-interval was recorded after 2 mg of bupivacaine, 4.5 mg of ropivacaine and 30 mg of lidocaine. Thus, the electrophysiological toxicity ratio was 15:6.7:1 (B:R:L). Provided local anaesthetic potency data can be extrapolated from the isolated nerve preparation to regional anaesthesia in humans, ropivacaine appears to provide a greater margin of safety than bupivacaine, if inadvertently injected into the venous circulation.