A new reversal for neuromuscular blockers

[wtbcrna, MSN, DNP, CRNA]

Anesthesiology. 2013 Aug;119(2):317-25. doi: 10.1097/ALN.0b013e3182910213.

[h=1]Calabadion: A new agent to reverse the effects of benzylisoquinoline and steroidal neuromuscular-blocking agents.[/h]

Hoffmann U, Grosse-Sundrup M, Eikermann-Haerter K, Zaremba S, Ayata C, Zhang B, Ma D, Isaacs L, Eikermann M.

[h=3]Source[/h]Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts, USA.

[h=3]Abstract[/h][h=4]INTRODUCTION:[/h]To evaluate whether calabadion 1, an acyclic member of the Cucurbit[n]uril family of molecular containers, reverses benzylisoquinoline and steroidal neuromuscular-blocking agent effects.

[h=4]METHODS:[/h]A total of 60 rats were anesthetized, tracheotomized, and instrumented with IV and arterial catheters. Rocuronium (3.5 mg/kg) or cisatracurium (0.6 mg/kg) was administered and neuromuscular transmission quantified by acceleromyography. Calabadion 1 at 30, 60, and 90 mg/kg (for rocuronium) or 90, 120, and 150 mg/kg (for cisatracurium), or neostigmine/glycopyrrolate at 0.06/0.012 mg/kg were administered at maximum twitch depression, and renal calabadion 1 elimination was determined by using a H NMR assay. The authors also measured heart rate, arterial blood gas parameters, and arterial blood pressure.

[h=4]RESULTS:[/h]After the administration of rocuronium, resumption of spontaneous breathing and recovery of train-of-four ratio to 0.9 were accelerated from 12.3 ± 1.1 and 16.2 ± 3.3 min with placebo to 4.6 ± 1.8 min with neostigmine/glycopyrrolate to 15 ± 8 and 84 ± 33 s with calabadion 1 (90 mg/kg), respectively. After the administration of cisatracurium, recovery of breathing and train-of-four ratio of 0.9 were accelerated from 8.7 ± 2.8 and 9.9 ± 1.7 min with placebo to 2.8 ± 0.8 and 7.6 ± 2.1 min with neostigmine/glycopyrrolate to 47 ± 13 and 87 ± 16 s with calabadion 1 (150 mg/kg), respectively. Calabadion 1 did not affect heart rate, mean arterial blood pressure, pH, carbon dioxide pressure, and oxygen tension. More than 90% of the IV administered calabadion 1 appeared in the urine within 1 h.

[h=4]CONCLUSION:[/h]Calabadion 1 is a new drug for rapid and complete reversal of the effects of steroidal and benzylisoquinoline neuromuscular-blocking agents.

http://www.ncbi.nlm.nih.gov/pubmed/23549405

[detroitdano]

Awesome stuff. Kind of one-ups Suggamadex with the benzylisoquinoline-reversal potential.

I can't believe we still don't have Suggamadex despite all the research out there saying it's perfectly safe and more cost-effective.

[wtbcrna, MSN, DNP, CRNA]

Yeah, but remember it takes about 17 years on average for research to be implemented into practice. The first article about Sugammadex was published in 2002, and it is still not been approved by the FDA in the United States.....

It is definitely interesting though!

[detroitdano]

Europe has been going through the stuff like water since 2008. I guess the FDA thinks the human body must act differently on the US continent.

[wtbcrna, MSN, DNP, CRNA]

Europe has been going through the stuff like water since 2008. I guess the FDA thinks the human body must act differently on the US continent.

Europe has always been our Phase IV testing site for new drugs....lol

[ssrhythm]

Awesome stuff. Kind of one-ups Suggamadex with the benzylisoquinoline-reversal potential.

I can't believe we still don't have Suggamadex despite all the research out there saying it's perfectly safe and more cost-effective.

The folks who have profited from succs and glyco and neostigmine for all these years are putting their hard-earned money to good use up on the hill. Anyone who thinks otherwise has their head buried in the sand. It is all about the money!

[puppies'n kittens]

Succ, neo and glycol are not on patent and there is very little profit with those drugs. One of the main reasons suggamandex was not approved was it was presented to the FDA right after the Vioxx debacle. That C2I was fast tracked through approval with disastrous results and they did not want to repeat that scenario. It will eventually be approved and will be used off label for veuronium and it is only going for approval for rocuronium and that is Organon's drug. If it is used for vecuronium it will be off label.