|Year : 2014 | Volume
| Issue : 1 | Page : 28-32
Efficacy of gabapentin versus pregabalin in pain control during and after panretinal laser photocoagulation
Hazem A Hazem, Jehan A Sayed
Department of Ophthalmology, Faculty of Medicine, Assiut University, Assiut, Egypt
|Date of Submission||12-Sep-2013|
|Date of Acceptance||13-Dec-2013|
|Date of Web Publication||21-Jun-2014|
Hazem A Hazem
MD, Faculty of Medicine, Assiut University, Assiut
Source of Support: None, Conflict of Interest: None
The aim of the study was to compare the analgesic efficacy and safety of pretreatment with oral gabapentin and its newer analog pregabalin for pain control during and after panretinal laser photocoagulation (PRP).
Patients and methods
The study included 60 eyes of 60 patients with proliferative diabetic retinopathy who were aged between 18 and 60 years and were candidates for PRP. Thirty patients (group A) received gabapentin 600 mg orally and group B received pregabalin 150 mg orally 2 h before PRP. Before sessions, all patients were instructed how to assess their pain level using the visual analog scale (VAS), and sessions were performed by the same ophthalmologist using as similar parameters as possible for each treatment plan. Blood pressure and heart rate were recorded just before, during, and immediately after each treatment session, and the VAS rates during (VAS I), 15 min after (VAS II), and 2 h after PRP session (VAS III) were collected; side effects for the study drugs were recorded for the same amount of time.
The mean age was 49.47 ± 7 years in group A and 50.33 ± 10 years in group B. The mean duration of session was 12 ± 1.8 min in group A and 11 ± 1.3 min in group B. Systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were significantly increased during sessions compared with baseline values in group A, whereas the increase in these parameters was not significant in group B. The median VAS both during the session (VAS I) and 15 min after the session (VAS II) was significantly lower in group B compared with group A, with no significant difference in the median pain score 2 h after session (VAS III) between both groups. The incidence of sedation and dizziness was significantly lower in group A compared with group B. More frequent nausea and vomiting were observed in group A compared with group B; however, this was not statistically significant.
In patients undergoing PRP, lower degree of pain associated with a better hemodynamic response was reported in those treated with preemptive 150 mg pregabalin compared with 600 mg gabapentin, suggesting that pregabalin may be better recommended for pain control during and immediately after PRP sessions.
Keywords: Gabapentin, pain, panretinal photocoagulation, pregabalin
|How to cite this article:|
Hazem HA, Sayed JA. Efficacy of gabapentin versus pregabalin in pain control during and after panretinal laser photocoagulation. J Egypt Ophthalmol Soc 2014;107:28-32
|How to cite this URL:|
Hazem HA, Sayed JA. Efficacy of gabapentin versus pregabalin in pain control during and after panretinal laser photocoagulation. J Egypt Ophthalmol Soc [serial online] 2014 [cited 2017 Jun 27];107:28-32. Available from: http://www.jeos.eg.net/text.asp?2014/107/1/28/134940
| Introduction|| |
Traditional treatment for proliferative diabetic retinopathy (PDR) is panretinal laser photocoagulation (PRP) by argon laser therapy. The diabetic retinopathy study research group (1981) identified the best results in terms of sight maintenance to be produced when a total of between 600 and 1600 laser burns of 500 μm are applied to the peripheral retina in a scatter manner.
Pain is the likely reason for the shortfall in the number of burns delivered. Patients frequently experience pain during PRP, which typically is in the moderate range .
Undertreatment could lead to accelerated loss of sight; hence, good pain management during PRP might significantly affect the rate of blindness within people with PDR .
To assist patient compliance during PRP, different techniques of anesthesia and analgesia have been used. Preprocedure or rescue retrobulbar or peribulbar injection anesthesia can be used to eliminate pain during the procedure, but it is invasive and imparts the risk for serious, although rare, complications and is difficult to apply in an outpatient setting .
Other pre-PRP analgesic techniques investigated include sub-Tenon anesthesia delivery, transcutaneous electrical nerve stimulation, and inhalation of Entonox (50: 50 nitrous oxide: oxygen gas); however, these methods are limited by their need for special equipment, invasiveness, or both. Oral analgesia is also widely used in pain control during PRP .
Pregabalin and gabapentin, the developmental predecessor of pregabalin, comprise an interesting class of drugs for pain control. These drugs differ structurally and mechanistically from other analgesics and also have efficacy in randomized trials for epileptic seizures and anxiety disorders. It was concluded that these drugs are not GABAergic and instead they reduce the stimulated release of excitatory transmitters by binding to calcium channel α2δ proteins. Both compounds also differ from GABA because they readily cross membrane barriers through system l-amino acid transporters .
Some clinical trials on gabapentin, or pregabalin given before a variety of surgical procedures producing visceral and somatic injury, have found a significant reduction in postoperative analgesic requirements as well as a reduction in early and late postoperative pain. In addition, some noticed that patients were hemodynamically stable. Pregabalin is several times more potent than gabapentin and has a more favorable pharmacokinetic profile, including dose-independent absorption .
This study aims to compare the analgesic efficacy and safety of pretreatment with oral gabapentin and its newer analog pregabalin for pain control during and after PRP.
| Patients and methods|| |
Study design and population data
This was a single-center, prospective, patient-masked, randomized study. After ethics committee approval and patients' informed consent, 60 eyes of 60 patients with PDR who were aged between 18 and 60 years and were candidates for PRP using argon laser were enrolled in our study.
Patients were excluded if they had serious medical problems within the last 6 months, including myocardial infarction (heart attack), congestive heart failure, stroke, deep vein thrombosis, pulmonary embolism, serious renal impairment, history of seizures or other neurologic disorders, and female patients intending to become pregnant or who were pregnant or nursing over the projected course of treatment. Patients currently taking gabapentin or pregabalin for other medical purposes or those with known allergic reaction to gabapentin or pregabalin from previous use were also excluded.
Patients were randomized into two equal groups of 30 patients each: group A received gabapentin 600 mg orally and group B received pregabalin 150 mg orally to control pain during the treatment session and during the early postoperative period (up to 2 h postoperative). Patients in both groups received the treatment 2 h before session. Study medication packages containing the appropriate products were premade by the hospital pharmacist, and none of the treating physicians, nurses, or patients knew what study group they were part of.
Before sessions, patients were instructed how to assess their pain levels using the visual analog scale (VAS), a well-documented method of pain assessment ranging from 0 to 10 (with 0 = no pain and 10 = the worst pain imaginable).
All patients underwent scatter PRP using the fundus contact lens (Ocular Mainster Ultrafield PRP; Ocular, Bellevue, Washington, USA), with coupling solution and two drops of benoxinate hydrochloride 0.4%. Laser treatment using an argon green laser machine (Visulas Argon II Plus; Carl Zeiss, Germany: Carl-Zeiss-Strasse 22, 73447, Oberkochen) was performed.
Argon laser PRP session parameters were set at spot size range from 200 to 350 μm, laser duration was set at 0.1 s, power enough to reach the end point blanching of retinal burn, and maximum of 600 laser burns was allowed during a treatment session.
Blood pressure and heart rate were recorded with a digital monitor just before, during, and immediately after the laser treatment.
Patients were asked to rate the level of pain they had felt during the PRP session (VAS I), 15 min after session (VAS II), and 2 h postoperatively (VAS III).
Any patient with VAS score of at least 4 received 1 mg/kg intramuscular diclofenac.
Side effects for the study drugs, such as sedation, dizziness, nausea, and vomiting, were recorded for the same amount of time.
SPSS (version 16; IBM Corporation 1 New Orchard Road Armonk, New York 10504-1722 United States) program was used for performing the statistical analysis. The comparison of the patient characteristics, session times, and perioperative hemodynamic changes between the two study groups was made using the independent t-test for 95% confidence interval of mean differences. Paired samples t-test was used to show perioperative hemodynamic changes inside each group independently.
Comparison of pain intensities by comparing the median values of the VAS between the two groups was performed by the Mann-Whitney U-test.
The χ-test was used to compare the side effects occurrence between the two groups.
| Results|| |
Patients' characteristics and duration of surgery were comparable in both groups [Table 1].
Perioperative hemodynamic monitoring showed a significant increase in the heart rate in both groups during and after sessions compared with the baseline value (P = 0.025 and 0.000), without a significant difference between both groups. Systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were significantly increased during the sessions compared with baseline values in the gabapentin group (P = 0.000); however, the increase in these parameters was not significant in the pregabalin group. No statistical difference was found between both groups concerning those parameters [Table 2].
The median pain score both intraoperatively (VAS I) and 15 min postoperatively (VAS II) was significantly lower in the pregabalin group compared with the gabapentin group (P = 0.000 and 0.006, respectively), with no significant difference in the median pain score 2 h after session (VAS III; P = 0.536) between both groups [Table 3] and [Figure 1].
The incidence of sedation and dizziness was significantly less in the gabapentin group (10 and 6.6%, respectively) compared with the pregabalin group (26 and 30%, respectively). More frequent nausea and vomiting were observed in the gabapentin group (26.6 and 13.3%, respectively) compared with the pregabalin group (16.6 and 6.6%, respectively), but these were not statistically significant [Table 4] and [Figure 2].
| Discussion|| |
In our study, the goal was to evaluate the analgesic effect of the preemptive analgesia with either gabapentin or pregabalin to find out a safe, noninvasive alternative to present treatment options for pain amelioration in patients undergoing PRP. Preemptive analgesia aims at attenuating the severity of pain forces starting by blocking the nervous system's usual response to pain. By preventing the sensitizing reaction to surgical treatment, the postoperative pain may be reduced .
Laser PRP was found to be painful by 88% of respondents in a survey by Richardson and Waterman  who found that pain is the likely reason for the shortfall in the number of burns delivered and ending PRP session before being complete. This 'undertreatment' could lead to the need for more sessions to complete the treatment as well as the risk of accelerated loss of sight . These results are in accordance with ours in this study, as most of our patients reported severe pain (VAS >4) indicating that PRP is a painful ophthalmic procedure.
However, the intraoperative and early postoperative pain relieve were better in the patients who received pregabalin. These findings follow the pharmacokinetic profile of pregabalin, which has an elimination half-life of 4.6-6.8 h after a single dose .
As the elimination half-life of gabapentin is 4.8-8.7 h, we chose to give the preemptive dose of the studied drugs 2 h before surgery because the maximal plasma level in humans is not reached before 2 h after oral administration .
As pain sensation and its quantification are subjective, we used VAS to assess the intensity of pain. VAS has been found to be correlative and reproducible .
Gabapentin and pregabalin inhibit Ca +2 currents by high-voltage activated channels containing the α2δ subunit, reducing neurotransmitter release and attenuating the postsynaptic excitability. They are antiepileptic drugs successfully used for chronic pain treatment. A large number of clinical trials indicate that gabapentin and pregabalin could be effective as perioperative and postoperative analgesics .
In our study, we used gabapentin at a dose of 600 mg and pregabalin 150 mg preemptively because administration of larger doses may increase the incidence and severity of side effects such as dizziness and somnolence as previously studied , and that would not be appropriate in this ambulatory surgical population based on previous clinical trials ,.
It is important to note that pregabalin was noted to result in better rates of successful pain management than gabapentin as observed during the intraoperative and early postoperative period, with no difference between the two drugs during the late postoperative period, and this may be in accordance with the results of the rodent model with chronic neuropathic pain, which stated that the analgesic potency of pregabalin is two-fold to four-fold greater than that of gabapentin .
Although the side effects (mainly sedation and dizziness) were significantly less pronounced in the gabapentin than the pregabalin group, these effects were not disabling. Nausea and vomiting were more frequent in the gabapentin group but without statistical significance.
Compared with gabapentin, pregabalin has a predictable and linear pharmacokinetics profile , which may be the cause that makes pregabalin more effective. To our knowledge, there have been no prospective randomized controlled clinical trials comparing pre-emptive oral gabapentin and pregabalin for pain control during and after PRP.
According to the American Academy of Ophthalmology (2011), there has been only one prospective cohort study comparing gabapentin with oxycodone-acetaminophen for the treatment of pain after photorefractive keratectomy. The patients' rating of their pain in both groups was similar, although gabapentin was associated with significantly more frequent use of anesthetic eye drops .
Another important observation, which is clinically and statistically observed, is that the PRP painful procedure triggered an increase in blood pressure in most of our patients, which was significantly attenuated in pregabalin-treated patients compared with gabapentin-treated patients.
An increase in systemic blood pressure during surgery indicates hemodynamic response to pain. Acute pain increases blood pressure by increasing the sympathetic activity .
Increasing evidence from animal and human research indicate a close relationship between the pain-regulating systems and blood pressure . The same brain stem nuclei and the same neurotransmitters, monoamines and endorphins, are associated with both functions ,.
Therefore, blood pressure changes can be viewed as a related evaluation of pain. This is also supported by increasing pulse in all our patients. The mechanism of gabapentinoids in controlling hemodynamic response remains unknown. However, they both bind to the α2δ subunit of the voltage-gated calcium channels , reducing the release of several excitatory neurotransmitter including glutamate, noradrenaline, and substance P ; possibly, they may have a similar action to calcium channel blockers.
In conclusion, there were lower degree of pain and better hemodynamic response reported by patients treated with preemptive 150 mg pregabalin, but they had more sedation and dizziness compared with 600 mg preemptive gabapentin. These findings suggest that pregabalin effect is modest and may be better recommended for patients undergoing PRP.
| Conclusion|| |
For patients undergoing PRP, lower degree of pain and better hemodynamic response were reported in those treated with preemptive 150 mg pregabalin compared with 600 mg gabapentin, suggesting that pregabalin may be better recommended for intraoperative and postoperative pain control for these patients.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
|1.||Wu WC, Hsu KH, Chen TL, Hwang YS, Lin KK, Li LM, et al. Interventions for relieving pain associated with panretinal photocoagulation: a prospective randomized trial. Eye 2006; 20:712-719. |
|2.|| Richardson C, Waterman H. Pain relief during panretinal photocoagulation for diabetic retinopathy: a national survey. Eye 2009; 23:2233-2237. |
|3.|| Weinberger D, Ron Y, Lichter H, Rosenbalt I, Axer-Siegel R, Yassur Y, et al. Analgesic effect of topical sodium diclofenac 0.1% drops during retinal laser photocoagulation. Br J Ophthalmol 2000; 84:135-137. |
|4.|| Cook HL, Newsom RS, Mensah E, Saeed M, James D, Ffytche T. Entonox as an analgesic agent during panretinal photocoagulation. Br J Ophthalmol 2002; 86:1107-1108. |
|5.|| Brodie MJ, Wilson EA, Wesche DL, Alvey CW, Randinitis EJ, Posvar El, Hounslow NJ. Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy. Epilepsia 2005; 46:1407-1413. |
|6.|| Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Perucca E, Tomson T. Progress report on new antiepileptic drugs: a summary of the Seventh Eilat Conference (EILAT VII). Epilepsy Res 2004; 61:1-48. |
|7.|| Woolf CJ, Chong MS. Preemptive analgesia, treating post-operative pain by preventing the establishment of central sensitization. Anesth Analg 1993; 77:362-379. |
|8.|| Frampton JE, Foster RH. Pregabalin in the treatment of postherpetic neuralgia. Drugs 2005; 65:111-118. |
|9.|| Beydoun A, Uthman BM, Sackellares JC. Gabapentin: pharmacokinetics, efficacy, and safety. Clin Neuropharmacol 1995; 18:469-481. |
|10.||1Scott J, Huskisson EC. Graphic representation of pain. Pain 1976; 2:175-184. |
|11.||1Dauri M, Faria S, Gatti A, Celidonio L, Carpenedo R, Sabato AF. Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences. Curr Drug Targets 2009; 10:716-733. |
|12.||1Arroyo S, Anhut H, Kugler AR, Lee CM, Knapp LE, Garofalo EA, Messmer S. Pregabalin add-on treatment: a randomized double-blind, placebo-controlled, dose-response study in patients with partial seizures. Epilepsia 2004; 45:20-27. |
|13.||1Pandey CK, Navkar DV, Giri PJ, Raza M, Behari S, Singh RB, Singh U, Singh PK. Evaluation of the optimal preemptive dose of gabapentin for postoperative pain relief after lumbar diskectomy. J Neurosurg Anesthesiol 2005; 17:65-68. |
|14.||1Jokela R, Ahonen J, Tallgren M, Haanpaa M, Korttila K. Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery. Br J Anaesth 2008; 100:834-840. |
|15.||1Bryans JS, Wustrow DJ. 3-Substituted GABA analogues with central nervous system activity: a review. Med Res Rev 1999; 19:149-177. |
|16.||1Steven AN, Rochelle ET, Anita BG, Josef FP. Oral Gabapentin for the treatment of postoperative pain after photo refractive keratectomy. Am J Ophthalmol 2008; 145:623-629. |
|17.||1Chawla PS, Kochar MS. Effect of pain and nonsteroidal analgesics on blood pressure. Wis Med J 1999; 98:22-29. |
|18.||1Schobel HP, Ringkamp M, Behrmann A, Forster C,Schmieder RE, Handwerker HO. Hemodynamic and sympathetic nerve responses to painful stimuli in normotensive and borderline hypertensive subjects. Pain 1996; 66:117-124. |
|19.||1Buscher HH, Hill RC, Romer D, Cardinaux F, Closse A, Hauser D, et al. Evidence for analgesic activity of enkephalin in the mouse. Nature 1976; 261:423-425. |
|20.||2Scriabine A, Clineschmidt BV, Sweet CS. Central noradrenergic control of blood pressure. Annu Rev Pharmacol Toxicol 1976; 16:113-123. |
|21.||2Taylor CP, Vartanian MG, Yuen P, Bigge C, Suman-Chauhan N, Hill DR. Potent and stereospecific anticonvulsant activity of 3-isobutyl GABA relates to in vitro binding at a novel site labelled by tritiated gabapentin. Epilepsy Res 1993; 14:11-15 . |
|22.||2Fink K, Dooley DJ, Meder WP, Suman CN, Duffy S, Clusmann H, Göthert M. Inhibition of neuronal Ca 2+ influx by gabapentin and pregabalin in the human neocortex. Neuropharmacology 2002; 42:229-236. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]