Adverse Cardiovascular Effects of Phenylephrine Eye Drops Combined with Intravenous Atropine

Background: Phenylephrine and atropine can cause serious adverse effects, when applied in combination. We investigated the effect of phenylephrine eye drops combined with intravenous atropine on the cardiovascular system in patients under general anaesthesia undergoing intraocular surgery. Methods: Thirteen patients undergoing intraocular surgery under general anaesthesia were observed in this study; all were injected intravenously with atropine due to the oculocardiac reflex during surgery. Fifty-four SD rats that received phenylephrine eye drops and intravenous atropine treatment under general anaesthesia were assessed, of which 24 treated with these drugs simultaneously were administered normal saline or antagonists. Blood pressure and heart rate were recorded and analysed. Findings: In patients, topical ocular application of 5% phenylephrine and intravenous atropine treatment led to a significant heart rate increase ten minutes after intravenous atropine treatment; the increase lasted 20 minutes. The significant increase in diastolic blood pressure (DBP) and systolic blood pressure (SBP) lasted 20 and 25 minutes, respectively. From five to 25 minutes after intravenous atropine treatment, SBP and DBP were both more than 20% higher than the at baseline. In rats, the blood pressure and heart rate changes were independent of the phenylephrine and atropine administration sequence but were related to the administration time interval. The variations in blood pressure and heart rate reached their peak when phenylephrine and atropine were administered simultaneously. The urapidil and neostigmine groups showed a significant decrease in blood pressure after the increase from the administration of phenylephrine and atropine. After neostigmine treatment, the heart rate was significantly lower than that associated with normal saline treatment. Interpretation: Phenylephrine eye drops combined with intravenous atropine treatment have obvious cardiovascular effects, which can be reversed by neostigmine. These drugs combination should be used carefully for ophthalmic surgery, especially in patients with cardiocerebrovascular diseases. Funding Statement: This work was supported by the Science and Technology Program of Guangzhou of Wei Chi (No. 201804010415). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: The use of experimental animals in this study complied with the animal ethics principles, and the protocol was approved by the laboratory animal ethics committee (No. 00201878).