Abstract

Surgical procedures require general anesthesia using combinations of drugs including fentanyl and/or lidocaine. Because many of these drugs have bimodal anticonvulsant/proconvulsant effects, they must be administered carefully. We herein report a case of seizure attack during anesthesia induction with low-dose fentanyl and lidocaine in a young child with no history of seizures. A 10-year-old girl was scheduled to receive an elective tenectomy. After a few seconds of fentanyl and lidocaine administration for anesthesia induction, she developed generalized tonic–clonic seizures. Seizures subsided spontaneously after 3 minutes. The patient's blood sugar, serum electrolytes, and arterial blood gas analysis were normal immediately after the event. She remained hemodynamically stable; however, the surgery was postponed after communication and discussion with the surgeon. Postoperatively, there was no evidence of postictal phase, and serum electrolytes and magnetic resonance imaging of the brain were normal. The patient had an uneventful recovery. However, electroencephalogram showed that hyperventilation stimulation test induced isolated epileptiform spikes over O1, suggesting a potential paroxysmal disorder over the left occipital area. This report is on a rare complication likely caused by fentanyl or lidocaine, which suggests that these drugs should be used cautiously in children whose clinical epileptic activities have been verified or are strongly suspected.

Keywords

anesthesia; children; fentanyl, lidocaine; seizures;

1. Introduction

Seizures are episodes of abnormally synchronized electrical brain activity. It is estimated that 2% of the general population will experience a seizure during their lifetime.¹ Benign childhood focal seizures affect 20–25% of children with nonfebrile seizures.² The typical onset is between 1 year and 12 years, with peak incidence at 5 years, and remission within 1–2 years from onset.³ In one third of the patients, seizures (or even partial status epilepticus) are single events in the child's life. The mean number of seizures is three and the maximum is 15. The new classification system of the International League Against Epilepsy Task Force identified three types of benign childhood focal seizures, namely, benign childhood epilepsy with centrotemporal spikes, early onset benign childhood occipital epilepsy (BCOE; Panayiotopoulos type), and late-onset childhood occipital epilepsy (Gastaut type).⁴ Although early onset BCOE is identified by occipital spikes on the electroencephalogram (EEG), they may also occur in children who do not suffer from seizures and in those with severe symptomatic epilepsies.

Several anesthetic and analgesic drugs may have both anticonvulsant and proconvulsant effects.⁵ For example, lidocaine at 0.5–5-μg/mL serum concentration is used to treat epileptic episodes, whereas higher doses are proconvulsant.⁶ In most cases, adult patients experience a brief general tonic–clonic (grand mal) seizure postoperatively.7, 8, 9 However, they occasionally develop grand mal seizures within seconds of anesthesia administration. A few adult patients have had a brief episode of grand mal seizure after receiving low-dose fentanyl.10, 11, 12 Two adults with a history of epilepsy suffered a grand mal seizure after low-dose lidocaine administration.¹³

Recently, a 4-month-old infant undergoing elective circumcision developed tonic–clonic convulsions after the administration of lidocaine.¹⁴ This case study suggested that infants and children are also susceptible to intraoperative anesthesia-induced seizures. Here, we report the case of a 10-year-old child, with no history of seizures, who required surgery for tenectomy due to wry neck (torticollis). The administration of low-dose fentanyl and lidocaine was followed by a brief episode of grand mal seizure. This report suggests that fentanyl or lidocaine should be used cautiously in children especially in those whose clinical epileptic activities have been verified or are strongly suspected.

2. Case Report

A 10-year-old girl (height, 146 cm; weight, 54 kg) was scheduled for an elective tenectomy of the left sternocleidomastoid muscle due to torticollis. She was robust and had no febrile convulsion or previous noteworthy medical history. She was previously never administered even dental anesthesia. In addition, she had no medical history of cardiovascular complications such as intracerebral abscess, neurological complications (epilepsy), or infections (viral encephalitis) that could predispose her to a seizure. At the time of admission, the laboratory data and physical examination showed no abnormalities (glucose, 105 mg/dL; blood urea nitrogen, 10 mg/dL; creatinine, 0.4 mg/dL; aspartate aminotransferase, 28 U/L; alanine transaminase, 25 U/L; Na⁺, 142 mmol/L; K⁺, 4.1 mmol/L; Cl⁻, 108 mmol/L; white blood cells, 7800/μL; hemoglobin b, 12.6 g/dL; platelet count, 169,000/μL; and prothrombin time/partial thromboplastin time/international normalized ratio, 9.7 s/26.2 s/0.9). She came to the operating room without any premedication. Blood pressure was 115/82 mmHg and heart rate was 75 beats/min. Under mask inhalation of 100% oxygen, 100 μg (1.85 μg/kg) of fentanyl was slowly administered intravenously in 30 seconds; 50 mg (0.93 mg/kg) of lidocaine was also administered intravenously in 3 seconds. Immediately after the administration of the lidocaine dose, the patient experienced general muscle contraction and rigidity, which were more prominent over the trunk and the upper and lower extremities. In addition, she had violent rhythmic muscle contraction and relaxation, and we also noted that she bit her tongue, clenched her tooth, and upper gazed. The probable general tonic–clonic seizure activity lasted for about 30 seconds.

She lost consciousness and did not respond to verbal commands soon after. Because the seizure activity was interfering with her breathing, bag–valve–mask (BMV) ventilation through the nose and mouth was initiated. After 3 minutes, the patient regained consciousness spontaneously, but the surgery was postponed.

On Day 1 following the seizure episode, the patient was tested for congenital heart disease or structural brain lesions by echocardiography, magnetic resonance imaging (MRI) of the brain, and EEG during hyperventilation stimulation testing. The echocardiogram and brain MRI results were normal. However, hyperventilation stimulation induced isolated spikes over O1 on the EEG, suggesting a paroxysmal neurological disorder in the lateral temporal to occipital area (Figure 1). Based on these findings and the short duration of the preoperative seizure, the patient was diagnosed with late-onset childhood occipital epilepsy (Gastaut type).

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Fig 1. Electroencephalogram report: hyperventilation stimulation test induced isolated spikes over O1 (black arrow), suggesting a paroxysmal disorder over the left occipital area.

Because the surgery was postponed, we transferred the patient to the pediatric intensive care unit for further observation and management. Fortunately, the patient was transferred to the general ward in 1 day as her condition stabilized and was discharged 2 days later without any neurological sequela.

Owing to the anesthesia-induced seizure, we discussed providing conservative treatment for wry neck with her parents, for which they agreed.

Written informed consent and informed assent were obtained from the parents and the patient, respectively.

3. Discussion

Surgical procedures commonly require general anesthesia using combinations of drugs including fentanyl and/or lidocaine. Because many of these drugs have bimodal anticonvulsant/proconvulsant effects, dosage guidelines are carefully designed for the safety of the patients.⁵ Herein, we reported the case of a 10-year-old child who suffered a grand mal seizure within seconds of receiving intravenous fentanyl (1.85 μg/kg) and lidocaine (0.93 mg/kg). The patient recovered spontaneously after 3 minutes. This adverse effect was not anticipated, because the patient had no medical history of spontaneous or anesthesia-related seizures. Based on the patient's age, the normal echocardiogram and MRI findings, but abnormal EEG finding during hyperventilation testing, the patient was diagnosed with late-onset childhood occipital epilepsy (Gastaut type).

Anesthesia-induced seizures have been reported with these drugs in adults13, 14, 15, 16, 17 and in an infant.¹⁴ Grand mal seizure was also reported in an adult who received fentanyl (2.53 μg/kg).¹⁰ Narcotic seizures were more likely to originate in the subcortical nuclei. Therefore, fentanyl may produce seizure activity in the subcortical areas, which would not be detectable by surface electrodes.¹⁸ However, hyperventilation stimulation induced isolated epileptiform spikes over the O1 area on the EEG. This suggested that the grand mal seizure in this case might be less related to fentanyl administration. Serum concentrations of lidocaine exceeding 5 μg/mL have been reported to lower the seizure threshold in the cerebral cortex, amygdala, hippocampus, and thus cause a generalized seizure.¹³ DeToledo et al¹³ reported that continuous intravenous infusions of lidocaine to 11 healthy volunteers at rates ranging from 1.5 mg/kg/min to 3 mg/kg/min resulted in generalized convulsions in all after an average total dose of 6–8 mg/kg. Modica et al⁵reported that a lidocaine dose of 16.5 mg/kg produced tonic–clonic seizure in 50% of patients. By contrast, in children receiving continuous infusions of lidocaine, adverse effects have been reported at levels of 1.8–4.7 μg/mL.¹⁹ From these reports, we can deduce that the dosage of lidocaine proconvulsant is lower in children than in adults. Just after the seizure episode, the patient was tested for congenital heart disease or structural brain lesions by echocardiography, MRI of the brain, and EEG during hyperventilation stimulation testing. Seneviratne et al²⁰ reported that hyperventilation action activating test may increase the rate of generalized discharges in children without epilepsy or other generalized epilepsies. The EEG results indicated that the occurrence of grand mal seizure behavior in this child was due to brain epileptogenic discharge. It was also deduced that the brain discharge was mainly caused after the administration of fentanyl and lidocaine. In theory, the lidocaine dose (0.93 mg/kg) administered was low and in itself should not induce convulsion. However, it is probable that the grand mal seizure may have occurred following the combined use of fentanyl with lidocaine in this case. These findings suggest that the serum toxic levels of fentanyl and lidocaine in children are different from those in adults, and that careful observation and management for children on lidocaine therapy is necessary, despite the range of serum lidocaine levels being within the therapeutic level. We also summarized the results of published papers on fentanyl or lidocaine-induced seizure in Table 1.

Table 1. Summary of literatures about fentanyl or lidocaine-induced seizure.

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Drug interactions have also been reported between lidocaine and fentanyl.²¹Cherng and Wong²² have demonstrated that fentanyl potentiated the lidocaine-induced convulsions in a dose-dependent manner in mice, and the effect may be mediated by an opioid mechanism. This study suggests that low-dose fentanyl may lower the threshold of lidocaine-induced seizure, especially in patients with characteristics of easy-provoked epileptiform discharge, as shown by the EEG in this child who received a low-dose fentanyl and lidocaine.

We also performed an echocardiography to detect whether the patient had any congenital heart disease, such as patent foramen ovale, ventricular septal defect, or atrial septal defect as even a small dose of fentanyl or lidocaine can induce seizure in these patients.²³

The management of anesthesia-induced seizures involves immediate deepening of anesthesia, administration of an anticonvulsant agent, and subsequent correction of any reversible precipitating factor.¹ In our case, treatment was not necessary, because after the BMV ventilation through her nose and mouth, the seizure subsided spontaneously and her vital signs stabilized. Based on these observations, we did not prescribe any anticonvulsant agent.

Our case report emphasizes five key points: (1) the serum toxic levels of fentanyl and lidocaine in children are different from those in adults. (2) Combination of fentanyl and lidocaine should be used very cautiously for potential cases in which epileptic activities are easy triggered. (3) Cardiogenic factors, such as congenital heart disease, should be kept in mind if seizure attack happened in the operation room without any obvious cause. (4) Although lidocaine lowers the occurrence of cough, laryngeal spasm, and arrhythmia when performing general anesthesia, it may not be routinely used in children. (5) One of the causes of acquired wry neck might be neurologic disorders in the central nervous system,²⁴ which could lower the threshold of seizure, and therefore, we should use fentanyl and lidocaine more carefully in these patients.

Acknowledgments

Thanks to all staff in the Tri-Service General Hospital, Taipei, Taiwan and Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.