title: Cardiovascular Adverse Effects of Phenylephrine Eyedrops: A Systematic Review and Meta-analysis.
abstract: OBJECTIVE
  Topical phenylephrine hydrochloride is routinely administered with few safety precautions, but evidence regarding its systemic safety to date is controversial. As even short-term variations in 24-hour blood pressure (BP) and heart rate (HR) can adversely affect cardiovascular health, better evidence on phenylephrine's effects on HR and BP is required.
  
  
  OBJECTIVE
  To perform a meta-analysis of available evidence regarding cardiovascular adverse effects of topical phenylephrine.
  
  
  METHODS
  PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews and Clinical Trials were searched for relevant literature from January 1, 1970, to January 1, 2014, using a combination of the following search terms: topical, ocular, ophthalmic, phenylephrine, tropicamide, cardiovascular effect, side effect, blood pressure, heart rate, mydriatic, and eye drops. A total of 70 articles related to the topic were identified and all full texts were retrieved.
  
  
  METHODS
  Randomized clinical trials reporting change in BP and HR for adults were included in this review. All studies reporting results for neonates or infants, not reporting standard deviations, or not specifying the time of measurement or the concentration of phenylephrine used were excluded.
  
  
  METHODS
  Data from randomized clinical trials that reported BP and/or HR as well as the time following administration of topical phenylephrine at which measurements were obtained by concentration of phenylephrine as a mean change and its standard deviation were extracted. Data were synthesized by concentration of phenylephrine and time of measurement following topical application using random-effects models with inverse variance weighting to account for heterogeneity across studies.
  
  
  METHODS
  Difference in BP and HR after topical administration of phenylephrine.
  
  
  RESULTS
  Eight RCTs with a total of 916 participants were included. Data were available for phenylephrine, 2.5%, at 20 to 30 minutes and 60 minutes or longer after administration, and neither BP nor HR changed at either time. Following application of phenylephrine, 10%, BP increased at 5 and 10 minutes (mean difference for both, +15 mm Hg; 95% CI, 11.94-18.54; P < .001) but decreased at 20 to 30 minutes and 60 minutes or longer with no changes detected against baseline. A mean increase in HR by 4.48 beats/min (95% CI, 1.09-7.88; P = .01) was present at 20 to 30 minutes following application of phenylephrine, 10%, and HR decreased by 60 minutes or longer with no changes detected compared with baseline.
  
  
  CONCLUSIONS
  Phenylephrine, 2.5%, leads to no clinically relevant change in BP or HR, and the changes in BP and HR seen with phenylephrine, 10%, are short lived. Thus, phenylephrine, 2.5%, is safe to use in clinical routine.
authors: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
authors: Bethany
authors: B
authors: Stavert
authors: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
authors: Myra B
authors: MB
authors: McGuinness
authors: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
authors: C Alex
authors: CA
authors: Harper
authors: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
authors: Robyn H
authors: RH
authors: Guymer
authors: Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
authors: Robert P
authors: RP
authors: Finger
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009883:Ophthalmic Solutions / Q000009:adverse effects; D010656:Phenylephrine / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D009883:Ophthalmic Solutions; D010656:Phenylephrine