The short to medium-term risks of intracameral phenylephrine.

PURPOSE: To compare outcomes and complications of patients undergoing phacoemulsification with and without the administration of intracameral phenylephrine.
MATERIALS AND METHODS: In this retrospective study, a chart review was performed. Two groups with an equal number of patients who did or did not receive intracameral phenylephrine during phacoemulsification were compared for differences in outcomes, risk factors and complications. The Chi-square test was used for comparison between groups. P<0.05 was statistically significant.
RESULTS: The two groups were well matched with regard to preoperative ophthalmic and systemic risk factors for complications and had very similar phacoemulsification power and time profiles. No differences in outcome were detected (P>0.05, all comparisons).
CONCLUSION: This retrospective study suggests that intracameral phenylephrine normalizes the intraoperative risk of small pupil cataract surgery and is not associated with an increased risk of systemic or postoperative ophthalmic complications.

INTRODUCTION

Intracameral phenylephrine, an α-1 adrenergic receptor agonist, is used in small pupil cataract surgery for mydriasis of the pupil and maintaining dilation throughout the procedure.1 Intracameral phenylephrine has also been instrument in preventing complications due to intraoperative floppy iris syndrome (IFIS), induced by tamsulosin23 or other α-1 adrenergic antagonists.4

Although there is evidence for safety of intracameral phenylephrine, some investigators remain concerned and suggest improvements.5 In particular some have reported that complications could theoretically include endothelial cell destruction syndrome, toxic anterior segment syndrome and endophthalmitis.5 Recent evidence suggests that intracameral phenylephrine may have an unacceptably high level of free radicals which may cause endothelial cell damage6 and the use of preservatives remains contentious.7 Additionally there is no consensus on the correct dosage of intracameral phenylephrine as the dose-response relationship is not linear.8

Theoretically, intraoperative intracameral phenylephrine may pose a systemic risk as phenylephrine is a vasopressor. Although the effect of intracameral phenylephrine on blood pressure has not been previously studied, topical phenylephrine and intracameral adrenaline/epinephrine have not been noted to have any statistically significant effect.9

Due to the increasing indications and use of intracameral phenylephrine for small pupil cataract surgery and the lack of safety data, we elected to perform a comparison of outcomes and complications of patients who did or did not receive intracameral phenylephrine during phacoemulsification.

MATERIALS AND METHODS

A chart review was performed of 50 patients who had received intracameral phenylephrine, and 50 patients who did not receive intracameral phenylephrine (control group) during phacoemulsification.

The operating theatre log book was used to select 50 patients who received intracameral phenylephrine during phacoemulsification, in chronological order. January 1, 2009 was chosen as the starting point for patient selection and the first 50 patients receiving intracameral phenylephrine meant the last patient underwent surgery on May 2010, a period of 17 months in total. Patients who received intracameral phenylephrine were selected purely on the basis of having undergone surgery by one surgeon (CW).

In each case the intracameral phenylephrine was composed of 0.3 ml of minims 2.5% phenylephrine hydrochloride (with sodium metabisulfite 0.075%, sodium edetate 0.0127%, and purified water) mixed with 0.3 ml of balanced salt solution (various manufacturers). This was mixed by the theatre scrub nurse and the entire 0.6 ml were injected in each case.

Patients in the control group had also undergone surgery at the same facility by the same surgeon as the study group. The control group received three doses of topical phenylephrine 2.5% and tropicamide 1% (Alcon Laboratories, Fort Worth, TX) prior to surgery with the phenylephrine group receiving additional intracameral phenylephrine, as detailed above. In order to equally spread the control group over the same 17-month period these 50 patients were each selected as the very next patient in chronological order who did not receive intracameral phenylephrine following the selection of a patient who had.

Surgical data, data on preoperative ophthalmic and systemic disease, operative details, intraoperative and immediate postoperative complications as well as data from the routine 4-week postoperative visit were collected for both groups. The 4-week postoperative visit included measurement of visual acuity, intraocular pressure as well as documentation of any new complications. Any subsequent complications or significant events since this 4-week visit were also noted. Comparisons were performed with the Chi-square. P<0.05 was considered statistically significant.

This is a purely retrospective analysis and thus did not require ethics approval. As such this study is not registered with the institutional review board (IRB) and the Declaration of Helsinki does not apply.

RESULTS

Completed data for all 100 patients were available. The mean age of the two groups were comparable at 74 years (range, 55-87 years) for those receiving phenylephrine versus 76 years (range, 59-91 years) for the control group. The reasons for using intracameral phenylephrine were small pupil (48 patients) and tamsulosin therapy (two patients). Preoperative ophthalmic and systemic risk factors for complications were also broadly comparable between groups (P>0.05 all comparisons; Table 1). Cardiovascular risk factors include previous myocardial infarction, hypertension, ischemic heart disease and diabetes, while respiratory risk factors included chronic obstructive pulmonary disease and asthma.

Table 1

Local and systemic risk factors for complications during cataract surgery for patients who did or did not receive intracameral phenylephrine

The operative details were remarkably similar between the groups (P>0.05 all comparisons; Table 2). All patients underwent the ‘phaco chop’ technique for cataract extraction. Intraoperative complications consisted of an anterior capsule rent in one patient in each group and a single posterior capsule rupture in the control group. There were no immediate postoperative complications in both groups in the recovery area and blood pressure readings were stable in all patients. No patients required an interim visit for any concerns between surgery and the 4-week visit.

Table 2

Operative details for phacoemulsification power and time for patients who did or did not receive intracameral phenylephrine

At 4-weeks postoperatively, intraocular pressure and visual acuity measurements were comparable in the two groups [Table 3]. Ophthalmic complications noted at the four week visit were a single case of corneal edema in each group, a single case of cystoid macular edema in each group and a case of postoperative uveitis in the group receiving phenylephrine. There were no systemic events noted in the intervening time in either group and no evidence of any attributable systemic event in any patient since the 4-week visit.

Table 3

Four-week postoperative data for patients who did or did not receive intracameral phenylephrine during phacoemulsification

DISCUSSION

Phenylephrine is a useful adjunct in small pupil cataract surgery as well as in patients susceptible to intraoperative floppy iris syndrome.124 Studies have demonstrated increased pupil dilatation following administration of intracameral phenylephrine and thus decreased risks of complications.124 The current study found almost identical intraoperative complications as well as postoperative outcomes suggesting that the addition of phenylephrine has normalized the risk in the small pupil group.

Currently, there is active discussion of the potential complications of intracameral phenylephrine.569 However, to our knowledge no study has directly compared outcomes between eyes receiving and eyes not receiving intracameral phenylephrine to ascertain any potential adverse events. A prospective, randomized, fellow eye study would be ideal to address such concerns.

Some studies have indicated that sodium metabisulfite, a chemical used to stabilize the phenylephrine molecule prior to use, may be potentially damaging to the cornea.10 In the current study we selected groups with very similar preoperative risk factors and operative details (apart from pupil size) indicating that any differences in outcomes would likely be due to the administration of phenylephrine intracamerally. We found no differences intraoperatively or postoperatively (P>0.05 all comparisons; Table 3).

While our outcomes suggest that administration of intracameral phenylephrine was not problematic and normalizes the risks of surgery in small pupil cases, one aspect remains unaddressed. Principally, if intracameral phenylephrine had been administered would the complication rate for this group have been higher? Although we cannot directly address this question from our outcomes, most ophthalmic surgeons would admit that a small pupil size is associated with higher incidences of operative complications8 in part due to the obstructed view and smaller rhexis. Hence a study that directly compares complication rates in eyes with large and small pupils when standardized methods of achieving mydriasis already exist (including intracameral phenylephrine) is of dubious ethical validity. Hence, the similar rates of complications between groups in the current study must be due to a reduction in the very real risk posed by small pupil sizes, because of the intervention.

One drawback of this study is the lack of data on pupil diameters pre- and post- dilation, to determine the significant difference in pupil size before the administration of intracameral phenylephrine. We do not routinely measure corneal pachymetry or endothelial cell counts in postoperative cataract cases but this information would also have been useful. Additionally the retrospective nature of the study is another drawback. However, the retrospective nature mitigated the likelihood of bias, as the surgeon was not aware at the time of the surgery that the complication rates would be examined in this manner. The operative notes are assumed to be correct as an exhaustive proforma is used by the surgeon that requires yes or no answers to a range of common complications as well as a free text box for the addition of further details. Perhaps transcription errors may have arisen in the completion of the operative notes but one would assume that this chance, however small, would be equal for both groups and thus not bias the results.

It is the policy of our department to review patients routinely at 4 weeks postoperatively unless an unexpected intraoperative event takes place, although patients are encouraged to call in the intervening time should they notice any signs or symptoms. The fact that none of our patients, from either group, were seen before 4 weeks is indeed encouraging. However, the possibility exists of corneal edema or some other complication developing that cleared by the time of the follow-up visit. We are assuming that the lack of patient contact before 4 weeks indicates no complication took place but concede that there is a source of potential error.

A large sample size would have allowed stronger conclusions, but in view of the lack of peer review studies directly comparing outcomes of patients receiving phenylephrine with those not receiving phenylephrine, this paper provides important clinical insights.

CONCLUSIONS

Small pupil diameters can cause problems during phacoemulsification and can be addressed by a variety of techniques, including administration of intracameral phenylephrine. Although this intervention is in widespread ophthalmic use, no study has yet been examined the safety of this medication intracamerally, despite the theoretical potential of several problems associated with its use. This retrospective study suggests that intracameral phenylephrine normalizes the intraoperative risk of small pupil cataract surgery and is not associated with any increased risk of systemic or postoperative ophthalmic complications.

The volume of published work in this area is small and due to the ubiquitous use of intracameral phenylephrine in cataract surgery, work studies are warranted to properly ascertain the safety of this medication to make cataract surgery safer.