About Naropin

Naropin (ropivacaine HCI) local anaesthetic

Naropin® (ropivacaine) is the most recent long-acting local anaesthetic introduced by Astra (AstraZeneca). Naropin is closely related to mepivacaine and bupivacaine, and was in fact synthetised simultaneously with those two local anaesthetics by af Ekenstam as early as in the mid 1950’s. Naropin was the first single-enantiomeric LA to be clinically introduced. It consists of only the S- enantiomer while mepivacaine and bupivacaine are racemates, i.e. they consist of equal amounts of R- and S-enantiomers. [1].

The reason for developing Naropin (ropivacaine) was the need for a long acting LA which is less cardiotoxic than bupivacaine [2, 3]. Several experimental and clinical studies confirm ropivacaine’s lower and different toxicity profile compared to bupivacaine [4-8]. The shorter side chain on the ropivacaine molecule (propyl-) reduces the lipid solubility to one third (1/3) of that of bupivacaine (butyl-), otherwise the physico-chemical properties of the two drugs are similar. Ropivacaine is produced as the single S-enantiomer, whereas bupivacaine is a racemic mixture of two enantiomers. Ropivacaine provides an approximately 10% shorter duration of analgesia and a 20% shorter motor block than bupivacaine. It has been demonstrated that ropivacaine is less cardiotoxic than bupivacaine, and it also presents a more distinct separation between sensory and motor blockade at the low concentration used for acute pain management (ref McClure, 1996, BJA, 76, 300 - 307). The motor block of ropivacaine, especially the lower concentrations (2 and 5 1-4 mg /ml) , is less profound than that of bupivacaine, while higher concentrations (7.5 and 10 mg/ml) provide profound motor block.

Naropin (ropivacaine) is indicated for epidural, intra-articular, major and minor nerve block and infiltration anaesthesia using the 7.5 & 10 mg /ml solutions in adults and the 5 mg /ml in children 1-12 years old. The 5 mg /ml solution can also be used for spinal (intrathecal) anaesthesia. For postoperative and labour pain management, the 2 mg /ml solution is recommended for epidural and major or peripheral nerve block via intermittent or continuous administration through an indwelling catheter [9]. Ropivacaine provides less intense motor block than bupivacaine [10].

Clinical studies show that epidural infusion of ropivacaine 2 mg /ml can provide adequate pain relief up to 72 hours after major abdominal surgery. The admixture of fentanyl 1-4 µg/ml improves pain control in a dose-dependent manner, although at the price of opioid side effects [11, 12].

Dag Selander MD, PhD
Consultant Medical Advisor

References

1. Af Ekenstam B, Egner B, Petersson G. Local Anaesthetics: 1. N-alkyl pyrrolidine and N-alkyl piperidine carboxylic amides. Acta Chemica Scandinavica 1957;11:1183-90.

2. Mc Clure JH: Ropivacaine. Brit J Anaesth1996; 76: 300-07

3. Albright GA. Cardiac Arrest Following Regional Anesthesia with Etidocaine or Bupivacaine. Anesthesiology 1979;51:285-7.

4. Reiz S, Häggmark S, Johansson G, Nath S: Cardiotoxicity of ropivacaine – a new amide local anaesthetic agent. Acta Anaesthesiol. Scand 1989; 33: 93-98

5. Groban L, Deal DD, Vernon JC, James RL, Butterworth J: Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine and ropivacaine in anesthetized dogs. Anesth Analg 2001; 97: 37-43

6. Dony P, Dewinde V, Vanderick B, Cuignet O, Gautier P, Legrand E, Lavand’homme P, De Kock M: The comparative toxicity of ropivacaine and bupivacaine at equipotent doses in rats. Anesth Analg 2000; 91: 489-92

7. Ohmura S, Kawada M Ohta T, Yamamoto K, Kobayashi T: Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats. Anesth Analg 2001; 93: 743-8

8. Knudsen K, Beckman Suurkula S, Blomberg S, Sjovall J, Edvardsson N. Central nervous and cardiovascular effects of i.v. infusion of ropivacaine, bupivacaine and placebo in volunteers. British Journal of Anaesthesia 1997; 78: 507 514

9.Wolff AP, Hasselström L, Kerkkamp HE, Gielen MJ: Extradural ropivacaine and bupivacaine in hip surgery. Brit J Anaesth 1995; 74: 458-60

10. Brodner G, Mertes N, van Aken H, et al: Epidural analgesia with local anesthetics after abdominal surgery: Earlier motor recovery with 0.2% ropivacaine than 0.175% bupivacaine. Anesth Analg 1999; 88: 128-33

11. Scott DA, Blake D, Buckland M, et al: A comparison of epidural ropivacaine infusion alone and in combination with 1, 2, and 4 µg /ml fentanyl for seventy-two hours of postoperative analgesia after major abdominal surgery. Anesth Analg. 1999; 88:857-64

12. Finucane BT, Ganapathy S, Carli F, et al: Prolonged epidural infusions of ropivacaine (2 mg/ml) after colonic surgery: the impact of adding fentanyl. Anesth Analg 2001; 92: 1276-85