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Grand Mal Convulsion After an Accidental Intravenous Injection of Ropivacaine

Dernedde, Mira, MD*; Furlan, Danièlle, MD*; Verbesselt, René, MD, PhD; Gepts, Elisabeth, MD*; Boogaerts, Jean G., MD, PhD*

doi: 10.1213/01.ANE.0000096008.24193.05
Case Reports: Case Report
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A 36-yr old, ASA physical status I patient scheduled for hip arthroplasty under regional anesthesia received at the end of surgery an IV injection of approximately 200 mL of a 0.15% ropivacaine solution (300 mg = 4.6 mg/kg) in approximately 5 min. The bag prepared for postopera- tive epidural infusion was accidentally connected to a peripheral IV line. The patient developed grand mal convulsions, hypotension, and respiratory arrest. No arrhythmias were observed. Twenty minutes after the event, the arterial plasma concentration of ropivacaine was 3.10 μg/mL. Using a pharmacokinetic model, the peak plasma concentration at the time of the accidental administration was estimated at 17.04 μg/mL. The patient recovered uneventfully.

IMPLICATIONS: An accidental IV injection of approximately 300 mg of ropivacaine was followed by seizures without any arrhythmia. The patient recovered uneventfully.

*Department of Anesthesiology, University Hospital Center, Charleroi and the

†Department of Clinical Pharmacology, University Hospital Center, Leuven, Belgium

Accepted for publication August 21, 2003.

Address correspondence to Dr. Mira Dernedde, Department of Anesthesiology, University Hospital Center, 92 boulevard P. Janson, 6000 Charleroi, Belgium. Address email to mira.dernedde@chu-charleroi.be.

Ropivacaine presents fewer central nervous system (CNS) and cardiovascular toxicities in animals (1,2) or humans (3,4) than bupivacaine. However, in clinical practice, the risk of systemic toxicity may also be affected by the relative potency and effectiveness of the two drugs when used for regional anesthesia (5). Some neurological events were reported after accidental intravascular administration of ropivacaine 1 (6–16). Plasma concentrations associated with these side effects were measured in volunteers, but thresholds for symptoms in patients are still not clear (3). A review of case reports shows a large interindividual variability regarding plasma concentrations and neurological and/or cardiovascular side effects when a large amount of the drug is given intravascularly in a short period of time (6–16). We report a case of grand mal convulsion that occurred in a patient after an accidental IV injection of ropivacaine. Arterial blood samples were taken for measurement of ropivacaine concentrations.

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Case Report

A 36-yr-old, 65-kg man (ASA physical status I) was scheduled for elective total hip arthroplasty. The patient was premedicated with midazolam. Arterial blood pressure was 120/75 mm Hg, and the heart rate was 60 bpm. He was placed in the lateral decubitus position, and a combined spinal epidural anesthesia was performed. Hyperbaric bupivacaine 10 mg, sufentanil 5 μg, and clonidine 50 μg were injected into the subarachnoid space. No anesthetic was administered in the epidural space, and no drug was given for sedation during surgery. The patient received supplemental oxygen 2 L/min by nasal cannula, and oxygen saturation remained at 98% until the end of surgery. After completion of the uneventful surgical procedure 53 min later, with the patient lying in the dorsal decubitus position and conversant, his speech was suddenly irrational. Mental confusion occurred with disorientation, major anxiety, and motor hyperactivity. He became unresponsive to verbal command and showed generalized tonic-clonic movements followed by loss of consciousness and respiratory arrest. Arterial blood pressure decreased to 65/35 mm Hg associated with light tachycardia 95 bpm (sinus rhythm). Ventilation was assisted with 100% oxygen and 10 mg ephedrine was injected IV. The seizures stopped after administration of propofol 70 mg IV. Tracheal intubation was facilitated with succinylcholine, and the lungs immediately hyperventilated. At this moment, the attending anesthesiologist realized that the patient had received IV 200 mL of a 0.15% ropivacaine solution in approximately 5 min (±300 mg = 4.6 mg/kg). This solution, prepared for postoperative pain management and accidentally connected to the peripheral IV line, was immediately replaced by a colloid solution. Sodium bicarbonate 100 mmol and ephedrine 20 mg were administered IV. Bicarbonate was given considering the frequent incidence of lactic acidosis after seizures (17,18). A radial artery catheter was inserted for hemodynamic control and blood sample removal. The first blood gas analysis performed 10 min after the end of seizure showed an acidosis (pH, 6.93; Pao2, 344 mm Hg; Paco2, 117.7 mm Hg; base excess [BE], −10.9; Sao2, 99.4%). Controlled hyperventilation was continued, and the patient was sedated with IV propofol. He remained hemodynamically stable without any sign of arrhythmia or QRS enlargement. Propofol administration was stopped 15 min later. After return of consciousness, the patient was tracheally extubated 15 min later and discharged in the postanesthesia care unit (PACU) for close observation. A second blood gas analysis was performed (pH, 7.33; Po2, 156.9 mm Hg; Pco2, 51.3 mm Hg; BE, 0.5; Sao2, 98.9%, without electrolyte disturbance). The patient had a complete recovery without any neurological sequel. The chest radiograph and the electrocardiogram performed in the PACU were unremarkable.

Arterial blood samples were withdrawn at different times after the episode and centrifuged, and plasma samples were stored at −20°C. Total plasma concentrations of ropivacaine were determined using high-performance liquid chromatography with a detection limit of 50 ng/mL. The plasma concentration of ropivacaine at 20, 90, and 150 min was 3.10, 1.94, and 1.47 μg/mL respectively. The peak plasma concentration immediately after the end of the injection period was estimated at 17.04 μg/mL using a 2-compartment pharmacokinetic model:C t =C αe−αt +C βe−βt, where C t is the plasma concentration at time point t in min, C α is the concentration in the α-compartment, C β is the concentration in the β-compartment, and α and β are the respective elimination constants (14). Considering that plasma binding of ropivacaine averaged 94 ± 1%, the calculated free fractions of the local anesthetic decreased as follows: 1.02, 0.19, 0.12, and 0.09 μg/mL respectively at the peak and after 20, 90, and 150 min (19).

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Discussion

This patient experienced a generalized tonic-clonic convulsion immediately after an accidental intravascular injection of around 300 mg ropivacaine. The absence of a history of any illness in our patient, especially epilepsy, the nonrecurrence of the convulsions, and the timing of the seizures in relation to administration of the local anesthetic were suggestive of a toxic reaction to the drug. The cardiovascular response was mild, and no arrhythmias were observed.

The potential interest of reporting the case is because of the large amount of inadvertently “perfused” local anesthetic and the relationships between the clinical signs of toxicity and plasma concentrations of the drug. This is the first report in which the local anesthetic has been administered directly through an IV cannula. In all previous cases, ropivacaine was injected intravascularly during performance of a regional anesthesia procedure (6–16). The ropivacaine concentrations calculated at the time of the episode and measured thereafter were clearly above the range of experimental human threshold for CNS toxicity symptoms (3,4).

Knudsen et al. (4) showed that after IV infusion of 10 mg/min ropivacaine in sedation-free volunteers, the arterial plasma concentration related to CNS symptoms is 4.3 ± 0.6 μg/mL, ranging between 3.4 and 5.3 μg/mL. The time between the end of the infusion and the disappearance of symptoms was 13 ± 11 min. Using a similar study design Scott et al. (3) found that the production of mild CNS toxicity symptoms (i.e., numbness of the mouth) occurred at plasma concentrations between 1 and 2 μg/mL and disappeared after 15 min. In these experiments, only subconvulsive concentrations of the local anesthetic were applied.

Several reports of CNS toxicity related to accidental intravascular injection of ropivacaine in patients have been published (6–16). In 1997, Selander et al. reviewed 2100 patients who had an epidural or peripheral nerve block performed with ropivacaine. Six patients (0.2%) presented signs of CNS toxicity without cardiac manifestation after accidental IV injection of doses varying from 75 to 200 mg. Thereafter, several reports described convulsions after accidental IV injection of ropivacaine in patients who had received different regional anesthetic techniques (6–16). According to these reports, sinus tachycardia was the most common cardiovascular response observed during the episode of convulsion. Ruetsch et al. (9) provided the only case report recounting the occurrence of severe cardiac dysrhythmia associated with convulsion in a patient accidentally receiving 225 mg ropivacaine IV. Seven minutes after completion of the injection, they reported a plasma concentration of the local anesthetic of 3.6 mg/mL. In our patient, we observed hypercapnia and acidosis after convulsion. During local anesthetic-induced seizures, carbon dioxide production and oxygen consumption are considerably increased (20). Acidosis decreases the protein binding of the drug and exacerbates local anesthetic-induced toxicity (20,21). However, we did not record any cardiac events.

Despite clearly written labels on the epidural preparation, it was nevertheless mistakenly connected to the peripheral IV line. The sequence of events and future avoidance of such error were discussed with everyone involved in the case.

In conclusion, accidental IV injection of a large dose of ropivacaine produced expected CNS symptoms without any cardiotoxicity.

We thank Dr Dobromir Dobrev from the Institute of Pharmacology and Toxicology, University of Dresden, Germany for expert technical advice regarding the calculation of the peak ropivacaine concentration.

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FOOTNOTES

1 Selander D, Sjövall J, Waldenlind L. Accidental IV injections of ropivacaine: clinical experiences of six cases [abstract]. Reg Anesth 1997;22:70.
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