Background
Generally, local anesthetics are well tolerated, however, several serious adverse events, local or systemic, are reported. Overall, ocular complications are commonly rare and have been reported as transient vision loss or amaurosis [
1‐
6], temporary paralysis of oculomotor muscles and cranial nerves III, IV and VI with diplopia [
1,
6], mydriasis [
1], Horner syndrome [
1,
7], ptosis [
8] and accommodation problems with both local ophthalmological and dental anesthesia. According to different authors and manifestation patterns, the prevalence after dental procedures is reported to be 1:1000 to 0,1% [
1] or even 0,7% [
9]. Usually, these complications are transient and disappear with ending of anesthetic effect. Several mechanisms and patterns as inadvertent intravascular injection or direct diffusion of local anesthetic solution to the eye socket after dental procedures as well as myotoxic effects are proposed [
5,
6,
8]. By interaction with eye vegetative nervous system, local anesthetics could affect the nerve endings directly, promoting sympathetic or parasympathetic damaging patterns [
1,
6]. Here, we present three cases with temporary amaurosis after subconjunctival application of mepivacaine 2% solution for laser cyclophotocoagulation (CPC) in patients with advanced refractory glaucoma.
Discussion and conclusions
We described three cases with temporary amaurosis after subconjunctival mepivacaine 2% administration for laser CPC in patients with advanced refractory glaucoma, two of which have been experienced on the same day and the third one about 9 months later. In our ophthalmological clinic, 1031 CPC procedures (using local anesthetics in nearly 95% of cases) were carried out in the past 3 years, without such complications experienced before. These three cases are not only special from a medical point of view as they represent complications that are little known so far, but also from the point of view of adequate risk management. The risk manager of our medical school was involved and elaborated an investigation plan.
For convenience, the relevant questions necessary to be addressed were separated into patient-related, drug-related and administration technique-related.
Patient-related aspects were: Which patients’ similarities predisposed to the observed complication? Why were at least two of them affected exactly on the same day?
Drug-related peculiarities: May any pharmaceutical problem, e.g. incorrect substance or vasoconstrictor co-mixture (e.g. adrenaline) in the local anesthetics vials be responsible? Could any drug-drug interaction explain the observed side effects?
Administration technique-related: Could any technical, procedural problem during local anesthetic administration be the clue? Further questions were as well: Which mechanism underlies the affection pattern? Would the re-exposition lead to the same pathological reaction? How could such complications be anticipated as well as be prevented in future? The patients’ thorough medical history analysis failed to reveal any peculiarities associated with general condition or co-morbidities. Moreover, in our first patient, the same procedure a day before performed on his right eye by the same ophthalmologist was well tolerated. Remarkably, the re-exposition with mepivacaine in the frame of laser CPC about 1,5 month later proceeded without any complication in both patients (the other, right eye of the first patient and the same eye of the second patient were treated). According to literature, the majority of patients experienced ocular side effects only once despite of repeated local anesthetics exposures [
1]. However, one case report described diplopia and external rectus muscle palsy in a woman on three consecutive local anesthesia with mepivacaine in dental settings [
10]. Most cases with ocular complications are reported for lidocaine (57%), articaine (19,3%), procaine (10,5%), and mepivacaine (7,9%) [
5]. In the vast majority of cases (94,5%), anesthetic solutions contained vasoconstrictors (e.g. adrenaline) [
5]. The prompted chemical analysis of the used mepivacaine vials via an independent laboratory (the Central Laboratory of German Pharmacists, Eschborn, Germany) excluded accidental adrenaline contamination during manufacturing process, and the investigated solutions contained solely the declared mepivacaine. Mepivacaine is a local anesthetic of the amide type with rapid action onset and reversible blockade of vegetative, sensor und motor nerve fibers as well as the heart conduction system. Our clinical pharmacological medication analysis revealed no drug-drug interactions between mepivacaine and patients’ co-medication. Moreover, the event time course (appearance after few minutes after mepivacaine administration), affection of only ipsilateral eye, medical history with no previous complications to mepivacaine as well as well-tolerated re-exposition argues against a causative role of drug-drug interactions and suggests a local affection as the cause. Both ophthalmologists were well experienced in the procedure and performed it without any remarkable technical difficulty which was confirmed by co-assisting colleagues as well.
Local anesthetics can elicit ocular complications during dental procedures reaching eye socket via vascular, neurological and lymphatic pathways [
11,
12]. Individual regional vascular-anatomical variations (anomalies) could predispose to such side effects [
6]. In case of ocular local anesthesia, the affection way may be shorter and easier. Several affection mechanisms are suggested in the frame of dental local anesthesia. An inadvertent intra-venous anesthetic injection could lead to cavernous sinus syndrome with preferential affection of nearest three oculomotor nerves (III, IV and VI) causing diplopia and muscle palsy. An accidental intra-arterial anesthetic injection may result in arterial terminal branch constriction either directly by admixtured vasoconstrictor or via sympathetic reflex activation due to direct mechanical arterial wall trauma resulting in transient pain, vision loss due to retinal vasoconstriction, regional skin and mucosal pallor as well as sensory deficits [
5,
6]. Neither of abovementioned symptoms was seen in our patients. Direct anesthetic tissue diffusion towards eye socket along with diffusion via bony openings is further pathways during dental anesthesia [
1,
6,
12]. Systemic symptoms (e.g. vasovagal reactions, tachyarrhythmia, palpitation, and anaphylactic reactions) are reported as well, however, have not been seen in our patients. In some cases, an ocular muscles mechanical trauma as well as myotoxic and neurotoxic action of anesthetic solutions are proposed as possible mechanisms [
8,
13].
Generally, two affection patterns, sympathetic and parasympathetic, have been discussed [
1,
6]. Preexisting Optic Nerve damage may increase the vulnerability to respective side effects. The parasympathetic affection pattern, resulting from blockage of ocular parasympathetic neural fibers at the ciliary ganglion level, located between Optic Nerve and external rectus muscle of the eye (eye socket) and facilitating pupil (ciliary muscle) constriction, would manifest as mydriasis, accommodation loss and absent ipsilateral direct and consensual light reflexes [
6]. Thus, we proposed that this may be the responsible mechanism also in our patients. It could be speculated that the anesthetic solution reached the ciliary ganglion via ciliary vessels exerting a neurotoxic reaction or ganglion anesthesia. Overall, despite of our thorough search, we could not find a satisfying answer to the justifiable question, why exactly these three patients from about annually treated 300 were affected.
We speculate that mepivacaine subconjunctival application provoked ipsilateral temporary amaurosis, mydriasis and light reflex absence by neurotoxic action on parasympathetic fibers at the ciliary ganglion level. Doctors should be aware and patients should be informed about such rare complications after local anesthetics administration. Adequate risk management should insure patients’ safety.
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