Eye (2006) 20, 712–719 & 2006 Nature Publishing Group All rights reserved 0950-222X/06 $30.00 www.nature.com/eye 1 2 1 1 CLINICAL STUDY Interventions W-C Wu , K-H Hsu , T-L Chen , Y-S Hwang , K-K Lin1, L-M Li1, C-P Shih2 and C-C Lai1 for relieving pain associated with panretinal photocoagulation: a prospective randomized trial Abstract mefenamic acid, and acetaminophen (either alone or in combination with each other) are Purpose To evaluate the efficacy of pain relief not effective in preventing PRP treatment- by oral diazepam, acetaminophen, mefenamic associated pain. Intramuscular injection of 1Department of acid, intramuscular ketorolac tromethamine, ketorolac tromethamine is also not effective in Ophthalmology, Chang and peribulbar anaesthesia in panretinal reducing PRP-associated pain. Gung Memorial Hospital, photocoagulation (PRP). Eye (2006) 20, 712–719. doi:10.1038/sj.eye.6701989; Taoyuan, Taiwan Methods A total of 220 patients with published online 8 July 2005 proliferative diabetic retinopathy requiring 2The Department of Business Administration, PRP treatment were enrolled in this study. Keywords: peribulbar anesthesia; pain; Chang Gung University, Before laser treatment, the patients were panretinal photocoagulation Taoyuan, Taiwan allocated randomly to one of eight groups: group 1: diazepam (n ¼ 22), group 2: Introduction Correspondence: C-C Lai, acetaminophen (n ¼ 21), group 3: mefenamic Department of acid (n ¼ 21), group 4: diazepam and Panretinal photocoagulation (PRP) is an Ophthalmology, Chang Gung Memorial Hospital, acetaminophen (n ¼ 22), group 5: diazepam effective treatment in reducing severe visual 5 Fu-Hsin St, Kwei-Shan, and mefenamic acid (n ¼ 22), group 6: loss in patients with proliferative diabetic 333, Taoyuan, peribulbar anaesthesia with lidocaine (n ¼ 23), retinopathy (PDR). 1–4 The Diabetic Retinopathy Taiwan group 7: intramuscular injection of ketorolac Study (DRS) recommended that treatment Tel: þ 886 3 3281200 ext. tromethamine (n ¼ 22), group 8: placebo consists of 800–1600 argon laser burns of 500 mm 8666; 1 Fax: þ 886 3 3287798. (n ¼ 67). Pain after the laser treatment was size to the peripheral retina in a scatter fashion. E-mail: ccl404@ assessed by a verbal descriptive scale. Blood However, previous studies have shown that adm.cgmh.org.tw pressure and heart rate were measured before PRP is a painful procedure for most patients.5–7 and after laser treatment. Therefore, to reduce patient suffering during Received: 26 April 2005 Results Patients receiving peribulbar PRP, some pain-reliving procedures are Accepted: 18 May 2005 anaesthesia had a significantly lower pain necessary when performing PRP. Published online: 8 July 2005 score than the control group (Po0.0001). There are several options to reduce pain Additionally, the peribulbar anaesthesia- associated with PRP performed on an None of the authors has any treated group had the significantly least outpatient basis. Retrobulbar anaesthesia, commercial or financial PRP-associated rise in either systolic peribulbar anaesthesia, and subtenon interests or conflicting (P ¼ 0.043) or diastolic blood pressure rates anaesthesia are effective pain-relieving relationships in respect to any products referred to in (P ¼ 0.030). There were no significant procedures, but are invasive for patients with 8–11 this article. differences in pain score using other potential complications. Transcutaneous anesthetic agents when compared with the electrical nerve stimulation has been advocated The paper has been control group. There were no significant in the practice of PRP, but special presented in part at the changes in heart rate after PRP treatment. instrumentation is required. Additionally, the Taiwan Academy of Ophthalmology Annual Conclusion Peribulbar anaesthesia is optimal setting of this treatment for ocular pain 12 Meeting, October 2004, effective in reducing pain and blood pressure remains to be determined. Oral or Taipei, Taiwan. increase after PRP treatment. Oral diazepam, intramuscular administration of anesthetic Interventions for PRP W-C Wu et al 713 agents is generally considered as a safe means of drug opaque, sealed envelopes until the patients were delivery with almost no ocular complications. To the best randomized in a 1 : 1 : 1 : 1 : 1 : 1 : 1 : 3 ratio to one of eight of our knowledge, the role of oral or intramuscular pain- groups: group 1 received an oral intake of 5 mg diazepam reliving agents in PRP has not been previously explored. (Valium, Roche, Basel, Switzerland); group 2 received an Only a few published studies have examined the various oral intake of 500 mg acetaminophen (Tylenol, McNeil anesthetic agents or techniques.5–7,12–14 Consumer and Specialty Pharmaceuticals, Ft Therefore, in this prospective study, we study whether Washington, PA, USA); group 3 received an oral intake of some commonly used oral or intramuscular anesthetic 500 mg mefenamic acid (Mefic, Pfizer, New South Wales, agents are as effective in reducing pain accompanying Australia); group 4 received 5 mg diazepam and 500 mg PRP treatment as peribulbar anaesthesia. The purpose of acetaminophen orally; group 5 received 5 mg diazepam this study is to reveal safer, noninvasive alternatives for and 500 mg mefenamic acid orally; group 6 received 4 ml pain control in patients receiving PRP treatment. Pain of peribulbar anaesthesia with 2% lidocaine (Xylocaine, ratings by the patients, blood pressure, and pulse were AstraZeneca AB, So¨derta¨lje, Sweden); group 7 received documented as subjective and objective indicators intramuscular injection of 30 mg ketorolac tromethamine related to pain. Blood pressure and pulse responses to (Torado, Roche Laboratories Inc., Nutley, NJ, USA); the pain stimulus, while not indicative of pain-specific and group 8 received no treatment as the control group. responses, were included as indicators of general body One of the authors was responsible for the drug arousal.15 It was predicted that effective interventions administration to the patients. Medications were given at would result in lower ratings of pain and decreased various time points before PRP treatment to achieve physiological reactivity relative to control subjects. maximal effect of the anesthetic agents according to the manufacturers’ recommendations. Timing of administration was as follows: oral drugs were given 2 h Patients and methods before PRP; peribulbar anaesthesia was performed half Subjects an hour before PRP; and intramuscular injection was performed 1 h before PRP. A prospective, randomized, study was performed to The procedure of peribulbar anaesthesia was evaluate the efficacy of various anesthetic agents during according to the previous published recommendation PRP treatment. The study was conducted in Chang Gung with modifications.16 In brief, peribulbar anaesthesia was Memorial Hospital after institutional review board performed using 2% lidocaine. This was injected through approval was obtained. The patient records were the lower eyelid immediately above the orbital rim at collected consecutively from April 2002 to May 2004. All the juncture of the medial two-thirds and lateral third patients gave informed consent. Patients with PDR, parallel to the orbital floor, and through the upper eyelid requiring PRP treatment as evidenced on fundus immediately below the upper eyelid at the juncture of the examination and fluorescein angiography, were medial third and lateral two-thirds parallel to the orbital included. Patients with following conditions were roof. The puncture was performed with a 25-gauge, excluded: PDR with concomitant neovascular glaucoma, 25-mm needle introduced completely through the skin. end-stage renal disease, abnormal liver function, poor The patient was then asked to move his eyes horizontally control of hypertension, patients with previous laser to make sure that no ocular perforation occurred. therapy, and patients with PDR combined with vitreous Lidocaine, 2 ml, was used for each injection. The haemorrhage requiring use of krypton red laser. Only procedure was performed with the eye in the primary one eye per person was included in the study. Patients’ position, followed by 10–15 min of ocular compression. demographic data, diabetes mellitus (DM) type, duration Adverse effects after drug administration were recorded. of DM, present medications, and presence of other If a patient was found to be allergic to the administered systemic diseases (hypertension, asthma, renal disease, medication, then the patient was given adequate and neuropathy) were recorded. The sample size of each treatment and dropped from this study. If the patient was group in this study was calculated as 18, with a unable to tolerate the pain during PRP, then retrobulbar significance levelr0.05 and a statistical power ¼ 0.8. The anaesthesia was performed. These patients were standard deviation of changes in systolic pressure was 23 subsequently dropped from this study. in this study. Laser application Randomization and drug delivery The pupils of patients in this study were dilated with 1% Allocation sequence was generated from random tropicamide (1% mydriacyl, Alcon Laboratories, number tables and concealed in sequentially numbered, Hempstead, UK) after the administration of the analgesic Eye Interventions for PRP W-C Wu et al 714 agents. After topical application of hydrochloride NC, USA). Statistical significance was accepted for P- (Novesin, Novartis, Hettlingen, Switzerland), the values smaller than 0.05. patients were instructed to sit before an argon green laser