Ropivacaine withdrawal syndrome: a case report / Síndrome de abstinência de ropivacaína: relato de caso

Abstract Introduction and objectives: Ropivacaine is a long-acting local anesthetic that causes prolonged anesthesia and is beneficial for a wide variety of surgeries. Systemic toxicity has been reported after usage of high dose ropivacaine or inadvertent intravascular administration. We report a case of ropivacaine withdrawal, which to our knowledge has not been previously described in the literature. Case report: The patient presented to our department with uncontrolled belt-like upper-abdominal pain, self-rated as a 9/10 on the numeric rating scale. We decided to use continuous epidural analgesia with ropivacaine through a multi-port epidural catheter. Pain was well controlled for one month without significant adverse effects. However, ropivacaine unexpectedly ran out and two hours later the patient developed agitation, generalized tremor, tachycardia, and tachypnea. These symptoms resolved 30 minutes after reinitiating epidural ropivacaine. Discussion: Our hypothesis of ropivacaine withdrawal was related to the timing of symptoms in relation to drug administration over two episodes. The possible mechanism of the observed withdrawal syndrome is upregulation of voltage-gated sodium channels after prolonged inhibition, resulting in increase in sodium influx and genetic variation.

Resumo Justificativa e objetivos: A ropivacaína é um anestésico local de ação prolongada indicado em uma ampla variedade de cirurgias. Toxicidade sistêmica tem sido relatada após o uso de dose alta de ropivacaína ou administração intravascular inadvertida. Relatamos um caso de crise de abstinência de ropivacaína que, até onde sabemos, não foi descrita anteriormente na literatura. Relato do caso: O paciente procurou nosso departamento com dor não controlada abdominal do tipo em cinta, avaliada pelo paciente como sendo 9/10 no escala de avaliação numérica. Decidimos usar analgesia peridural contínua com ropivacaína através de cateter peridural multiperfurado. A dor foi bem controlada por um mês sem efeitos adversos significativos. No entanto, a ropivacaína inesperadamente se esgotou e, duas horas depois, o paciente desenvolveu agitação, tremor generalizado, taquicardia e taquipneia. Esses sintomas regrediram completamente 30 minutos após o reinício da ropivacaína por via peridural. Discussão: Nossa hipótese de abstinência de ropivacaína foi relacionada à cronologia dos sintomas em relação à administração da droga ao longo de dois episódios. O possível mecanismo da síndrome de abstinência observada é a regulação positiva dos canais de sódio dependentes de voltagem após inibição prolongada, resultando em aumento do influxo de sódio e variação genética.

Simultaneous Determination of Ropivacaine and 3-Hydroxy Ropivacaine in Cerebrospinal Fluid by UPLC-MS/MS.

In this paper, a UPLC-MS/MS method was developed for the determination of ropivacaine and its metabolite 3-hydroxy ropivacaine in cerebrospinal fluid. The cerebrospinal fluid was processed by ethyl acetate liquid-liquid extraction. The multiple reaction monitoring (MRM) mode was used for quantitative analysis by monitoring the transitions of m/z 275.3 → 126.2 for ropivacaine, m/z 291.0 → 126.0 for 3-hydroxy ropivacaine, and m/z 290.2 → 198.2 for the internal standard. Standard curves for ropivacaine and 3-hydroxy ropivacaine in cerebrospinal fluid were conducted over the concentration range of 0.2-2000 ng/mL, demonstrating excellent linearity, and the lower limit of quantification was 0.2 ng/mL. The intraday precision of ropivacaine and 3-hydroxy ropivacaine was less than 11%, while the interday precision was less than 7%. The accuracy ranged between 87% and 107%, the average extraction efficiency was higher than 79%, and the matrix effect was between 89% and 98%. The developed method was then applied to a case of suspected poisoning of ropivacaine.