, Volume 60, Issue 5, pp 1065–1093 | Cite as


An Update of its Use in Regional Anaesthesia
  • Karen J. McClellanEmail author
  • Diana Faulds
Adis Drug Evaluation



Ropivacaine is a long-acting, enantiomerically pure (S-enantiomer) amide local anaesthetic with a high pKa and low lipid solubility which blocks nerve fibres involved in pain transmission (Aδ and C fibres) to a greater degree than those controlling motor function (Aβ fibres). The drug was less cardiotoxic than equal concentrations of racemic bupivacaine but more so than lidocaine (lignocaine) in vitro and had a significantly higher threshold for CNS toxicity than racemic bupivacaine in healthy volunteers (mean maximum tolerated unbound arterial plasma concentrations were 0.56 and 0.3 mg/L, respectively).

Extensive clinical data have shown that epidural ropivacaine 0.2% is effective for the initiation and maintenance of labour analgesia, and provides pain relief after abdominal or orthopaedic surgery especially when given in conjunction with opioids (coadministration with opioids may also allow for lower concentrations of ropivacaine to be used). The drug had efficacy generally similar to that of the same dose of bupivacaine with regard to pain relief but caused less motor blockade at low concentrations.

Lumbar epidural administration of 20 to 30ml ropivacaine 0.5% provided anaesthesia of a similar quality to that achieved with bupivacaine 0.5% in women undergoing caesarean section, but the duration of motor blockade was shorter with ropivacaine. For lumbar epidural anaesthesia for lower limb or genitourinary surgery, comparative data suggest that higher concentrations of ropivacaine (0.75 or 1.0%) may be needed to provide the same sensory and motor blockade as bupivacaine 0.5 and 0.75%. In patients about to undergo upper limb surgery, 30 to 40ml ropivacaine 0.5% produced brachial plexus anaesthesia broadly similar to that achieved with equivalent volumes of bupivacaine 0.5%, although the time to onset of sensory block tended to be faster and the duration of motor block shorter with ropivacaine.

Ropivacaine had an adverse event profile similar to that of bupivacaine in clinical trials. Several cases of CNS toxicity have been reported after inadvertent intravascular administration of ropivacaine, but only 1 case of cardiovascular toxicity has been reported to date. The outcome of these inadvertent intravascular administrations was favourable.

Conclusion: Ropivacaine is a well tolerated regional anaesthetic with an efficacy broadly similar to that of bupivacaine. However, it may be a preferred option because of its reduced CNS and cardiotoxic potential and its lower propensity for motor block

Pharmacodynamic Properties

The amide local anaesthetic ropivacaine reversibly blocks nerve impulse conduction by reducing nerve cell membrane permeability to sodium ions. In vitro studies have shown that, because of its high pKa (≈8.2) and low lipid solubility, the drug preferentially blocks nerve fibres responsible for pain transmission (Aδ and C fibres) rather than motor function (Aβ fibres). In isolated rabbit vagus nerve, ropivacaine caused significantly less blockade of motor fibres than bupivacaine (p = 0.0001) but had a similar effect on sensory fibres.

Ropivacaine appears to be less cardiotoxic than equal concentrations of racemic bupivacaine because of its faster dissociation from cardiac Na+ channels, but more cardiotoxic than lidocaine (lignocaine). The drug had a smaller effect on QRS prolongation than bupivacaine in healthy volunteers (+2.4 vs +6%; p < 0.05). CNS toxicity occurs at lower plasma concentrations than cardiotoxicity with all local anaesthetics; ropivacaine and bupivacaine caused seizures at lower concentrations than lidocaine in dogs.

In healthy volunteers, ropivacaine had a significantly higher threshold for CNS toxicity (lightheadedness, tinnitus and numbness of the tongue) than bupivacaine, with mean maximum tolerated unbound arterial plasma concentrations of 0.56 and 0.3 mg/L, respectively (p < 0.001).

Ropivacaine has a biphasic vascular effect, causing vasoconstriction at low concentrations but not at higher concentrations. Importantly, epidural ropivacaine 0.5% did not compromise uteroplacental circulation in healthy pregnant women.

Pharmacokinetic Properties

After epidural administration in women undergoing caesarean section, mean maximum plasma concentrations (Cmax) of 1.1 to 1.6 mg/L were reached after administration of 20 to 28ml ropivacaine 0.5 or 0.75%. The drug also underwent a degree of systemic absorption after intercostal, subclavian perivascular, peribulbar, intra-articular or local administration. However, because ropivacaine is extensively (90 to 94%) bound to plasma proteins (mostly α1-acid glycoprotein) after systemic absorption, Cmax for unbound drug remained well below the threshold for CNS toxicity reported in volunteers (≈0.6 mg/L) regardless of the route of administration. Like bupivacaine, ropivacaine crosses the human placenta.

Mean total body clearance and terminal elimination half-life of ropivacaine after epidural administration in pregnant women ranged from 13.4 to 19.8 L/h and 5 to 7h, respectively.

Ropivacaine undergoes extensive hepatic metabolism after intravenous administration, with only 1% of the drug eliminated unchanged in the urine. Two cytochrome P450 (CYP450) isoenzymes, CYP1A2 and CYP3A4 are responsible for the formation of major (3-hydroxy-ropivacaine) and minor metabolites, respectively. Agents which inhibit these isozymes (particularly CYP1A2) have the potential to affect the pharmacokinetic profile of ropivacaine. Accordingly, coadministration of fluvoxamine, a CYP1A2 inhibitor, significantly increased total plasma concentrations of intravenous ropivacaine by 16% and delayed its elimination.

Therapeutic Efficacy

Ropivacaine has been extensively evaluated for use as an analgesic (for labour or postoperative pain) and as a regional anaesthetic during a variety of surgical procedures.


Epidural ropivacaine 0.2% provided adequate pain relief when used for the initiation (10 to 18ml) and maintenance (4 to 10 ml/h) of labour analgesia and had efficacy generally similar to that of the same dose bupivacaine with regard to pain relief and motor blockade (mild) in comparative studies. Ropivacaine, like bupivacaine, had no significant effects on neonatal outcome. Coadministration with opioids such as fentanyl and sufentanil improved labour analgesia and allowed a lower concentration of the anaesthetic to be used (at these lower concentrations ropivacaine caused less motor blockade than bupivacaine).

Lumbar or thoracic epidural ropivacaine 0.1, 0.2 and 0.3% infused at 10 ml/h for 21 hours after abdominal or orthopaedic surgery reduced morphine requirements (the primary end-point) compared with placebo. The incidence of motor block increased with increasing dose but did not differ significantly from that reported in placebo recipients. Results from comparative studies suggest that epidural ropivacaine 0.2% is more effective than patient-controlled intravenous morphine for postoperative pain relief. As for labour pain, combination with opioids is effective and may allow a lower concentration of ropivacaine to be used for the same level of pain relief.

Preoperative (along the intended line of the incision) or postoperative wound infiltration of 30 to 40ml ropivacaine 0.25 or 0.5% dose-dependently relieved postoperative pain after hernia repair; a higher concentration (0.75%) was as effective as bupivacaine 0.25%. Evidence published in abstract form suggests that preoperative infiltration of the incision line using ropivacaine may also provide pain relief after thoracic surgery, breast reconstruction or lower back surgery, and postoperative wound infiltration alleviates pain after shoulder surgery.

Evidence indicates that epidural ropivacaine 0.2 and 0.25% (2 and 2.5 mg/kg) may provide effective postoperative analgesia when given via the caudal route in children undergoing minor surgery, and by the lumbar route in those undergoing major surgery. Importantly, motor block upon awakening was minimal with ropivacaine in these studies.


Lumbar epidural administration of 20 or 30ml ropivacaine 0.5% provided anaesthesia of a similar quality to that achieved with bupivacaine 0.5% in women undergoing caesarean section, without affecting neonatal outcome. The drugs had comparable effects on sensory blockade, but motor blockade tended to be shorter with ropivacaine. Lumbar epidural ropivacaine 0.5 to 1% also provided effective anaesthesia for lower limb or genitourinary surgery, although comparative data suggests that higher doses of ropivacaine (0.75 or 1%) may be needed to provide the same pattern of sensory and motor blockade as bupivacaine 0.5 and 0.75% in these patients.

In patients about to undergo upper limb surgery, 30 to 40ml ropivacaine 0.5% produced a pattern of brachial plexus anaesthesia broadly equivalent to that achieved with bupivacaine 0.5% whether administered via the subclavian perivascular, axillary or interscalenic approach. The onset of sensory blockade tended to be faster and the duration of motor blockade shorter with ropivacaine, but between-group differences only reached statistical significance in 1 study. In noncomparative studies, anaesthesia of brachial plexus dermatomes was achieved in ≥86% of patients who received 30 to 33ml ropivacaine 0.5% via the subclavian perivascular route.

Limited data indicate that 25 to 30ml ropivacaine 0.75% had an onset of sensory block similar to that of the fast onset/medium duration local anaesthetic mepivacaine 2% (≈25ml) when used for combined sciatic-femoral nerve block for lower limb surgery, but provided longer postoperative analgesia. This advantage was offset by a longer time to resolution of foot motor block. Limited data suggest that ropivacaine 0.5% has an anaesthetic efficacy similar to that of bupivacaine 0.5% when used for combined lumbar plexus-sciatic nerve block (for knee surgery) and 3-in-1 block (for hip surgery after trauma).

Results from a number of well controlled trials suggest that 5 to 10ml ropivacaine 1% (alone or with lidocaine) provides a quality of peribulbar anaesthesia at least similar to that achieved with 5 to 10ml bupivacaine 0.5 or 0.75% (alone or with lidocaine) in patients undergoing eye surgery.


Ropivacaine was well tolerated in clinical trials, although few studies provided detailed tolerability data. Hypotension was the most commonly reported adverse event in studies of epidural ropivacaine but this was most likely a consequence of sympathetic block (common to all local anaesthetics). Other reported events included nausea, vomiting, paraesthesia, urinary retention and bradycardia. The tolerability profile of ropivacaine was similar to that of bupivacaine in comparative studies. Limited evidence also suggests that the drug is well tolerated after brachial plexus block, intrathecal administration, lumbar plexus-sciatic nerve block, local wound infiltration and peribulbar administration. The clinical experiences from 60 studies involving 3000 patients showed that accidental intravascular administration of ropivacaine occurred in 6 patients. Only 1 patient convulsed and none showed signs of cardiotoxicity at doses of 75 to 200mg. The outcome of all 6 patients to these reactions was good. Consistent with preclinical evidence that cardiovascular toxicity occurs at higher plasma concentrations than CNS toxicity, only 1 case of cardiovascular toxicity after intravascular administration of ropivacaine has been reported to date.

Dosage and Administration

Ropivacaine 0.2% is recommended for epidural analgesia, administered via either lumbar or thoracic routes (6 to 14 ml/h) after surgery for postoperative pain and via the lumbar route for labour pain (10 to 20ml bolus then 6 to 14 ml/h plus top-up if required). For anaesthesia during caesarean section, ropivacaine 0.75% (15 to 20ml) is recommended. This concentration is also recommended for major or minor nerve block and wound infiltration whereas ropivacaine 0.75 and 1.0% can be used for lumbar epidural anaesthesia during other types of surgery.

Administration of ropivacaine to children <12 years of age or for spinal anaesthesia in adults is not yet recommended.


Bupivacaine Ropivacaine Sufentanil Levobupivacaine Motor Block 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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© Adis International Limited 2000

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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