Kuruvilla R, Sahu PD, Meltzer MA. Systemic Uptake of Chlorpromazine After Delivery via Retrobulbar Injection. Arch Ophthalmol. 2012;130(10):1348-1349. doi:10.1001/archophthalmol.2012.662
Author Affiliations: Department of Ophthalmology, Mount Sinai School of Medicine, New York, New York.
Severe pain can manifest in blind eyes as well as eyes with useful vision.1 Patients who fail conservative therapy with oral analgesics or topical steroid and cycloplegic eyedrops can undergo more aggressive measures. Although enucleation is the definitive treatment, some patients may not be medically or psychologically ready for this.2 As an alternative, retrobulbar alcohol injections can be used. More recently, chlorpromazine, a phenothiazine-class antipsychotic, has gained popularity. Initially described in the 1980s, reports have suggested that it provides superior pain control with a good response rate and fewer complications than alcohol injections.1,3 Previously reported adverse effects due to chlorpromazine injections have all been localized to the intraorbital or periorbital region. Herein, we describe a patient treated with retrobulbar chlorpromazine injection who subsequently developed systemic symptoms similar to those observed in patients receiving enteral chlorpromazine.
A 63-year-old woman visited our clinic 10 years after surgical repair for total rhegmatogenous retinal detachment in her right eye at an outside hospital. Her visual acuity was hand motions, with an afferent pupillary defect and intraocular pressure of 42 mm Hg. B-scan ultrasonography showed persistent retinal detachment.
A retrobulbar injection was performed to alleviate her ocular pain. Two milliliters of 25-mg/mL chlorpromazine was injected with a retrobulbar needle, taking care to ensure the drug was not injected into any major vessels. No local anesthesia was used and no complications were noted during the procedure. The patient left our clinic in stable condition but returned to the hospital 1 hour later with dizziness and palpitations. Her vital signs were unremarkable but her right infraorbital area showed moderate painless swelling without erythema. There were mild conjunctival injection and chemosis but no proptosis, ptosis, or motility deficits. Visual acuity remained unchanged and intraocular pressure was 11 mm Hg. A serum phenothiazine panel drawn 3 hours after injection revealed the concentration of chlorpromazine to be 20 ng/mL (minimum reporting limit was 10 ng/mL). The patient was placed on electrocardiographic monitoring, and her symptoms eventually resolved without intervention. She was discharged from the emergency department and was followed up in our clinic the following day. She reported no further systemic symptoms, her periorbital swelling had resolved, and her eye pain remained subsided.
Chlorpromazine reaches therapeutic systemic levels when used at an oral dosage of 200 to 400 mg/d. Common adverse effects of retrobulbar chlorpromazine injections include transient palpebral edema and chemosis. Transient ptosis, sterile orbital cellulitis, chronic orbital inflammation, neurotrophic corneal ulcer formation, and pigmentary degeneration of the retina have also been described.2- 4 Of the 9 patients in the series by Estafanous et al,1 1 developed nausea and vomiting followed by a brief episode of loss of consciousness. Per the authors' report, it was unclear whether the latter reaction could be directly attributed to the injection or represented a vasovagal response. In the case series of 20 patients by Chen et al2 and the report of 60 patients by McCulley and Kersten,3 no systemic complications were noted.
To our knowledge, this is the first case of adverse effects experienced by a patient after retrobulbar chlorpromazine injection due to infiltration of the drug into systemic circulation. We hypothesize that the mechanism of systemic delivery was either infiltration of the drug into one of the smaller arterioles of the retrobulbar compartment or extravasation through the dural sheath. The latter mechanism would seem more likely considering the 1991 radiographic study by Zahl et al5 that revealed tracking along the optic nerve sheath and intracranial spread of local anesthetic after a peribulbar injection.
In summary, we urge caution and vigilance during and after retrobulbar chlorpromazine injections. Although the risk of systemic spreading of any medication injected into the retrobulbar space is small, awareness of the anticholinergic and α-adrenergic antagonistic activity of chlorpromazine is vital for patient counseling and treatment.
Correspondence: Dr Meltzer, Department of Ophthalmology, Mount Sinai School of Medicine, One Gustave L. Levy Place, PO Box 1183, New York, NY 10029 (firstname.lastname@example.org).
Financial Disclosure: None reported.