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Randomized controlled trial of intra-articular ketorolac on pain and inflammation after minor arthroscopic knee surgery.
Solheim, N, Gregersen, I, Halvorsen, B, Bjerkeli, V, Stubhaug, A, Gordh, T, Rosseland, LA
Acta anaesthesiologica Scandinavica. 2018;(6):829-838
Abstract
BACKGROUND Ketorolac is an effective non-steroidal anti-inflammatory drug, commonly used with local anaesthetics as part of local infiltration analgesia protocols following orthopaedic surgery. However, systemic uptake and drug action may be the major mechanism after local infiltration. The aims of this project were to study the effects of a small, systemically ineffective dose of ketorolac given intra-articularly for post-operative pain and also to study synovial inflammatory biomarkers. We investigated whether ketorolac affects pro-inflammatory biomarkers in an in vitro model, as well. METHODS In this placebo-controlled, blind, randomized study, we analysed intra-articular ketorolac (5 mg) in ambulatory minor knee surgery patients with moderate or severe pain (n = 44). We assessed post-operative pain intensity (n = 44) and analysed microdialysis samples taken from knee synovial tissue every 20 min (n = 34). We also tested cyclooxygenase-independent effects of ketorolac in synovial cells stimulated by prostaglandin E2 and chondroitin sulphate in vitro. RESULTS Intra-articular ketorolac (5 mg) administration did not reduce pain or synovial pro-inflammatory cytokines CXCL1, IL-8, and MCP-1, 0-120 min after knee arthroscopy. Female gender was a risk factor for moderate or severe pain (relative risk 1.45, 95% confidence interval 1.04-2.01). Paradoxically, ketorolac increased the release of CXCL1 and IL-8 in prostaglandin E2 and chondroitin sulphate-stimulated synovial cells in vitro. CONCLUSION Ketorolac prescribed at a low dose intra-articularly does not produce any detectable analgesic effect after minor knee surgery.
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Ketorolac for postoperative pain in children.
McNicol, ED, Rowe, E, Cooper, TE
The Cochrane database of systematic reviews. 2018;(7):CD012294
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Abstract
BACKGROUND Children who undergo surgical procedures in ambulatory and inpatient settings are at risk of experiencing acute pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce moderate to severe pain without many of the side effects associated with opioids. However, NSAIDs may cause bleeding, renal and gastrointestinal toxicity, and potentially delay wound and bone healing. Intravenous administration of ketorolac for postoperative pain in children has not been approved in many countries, but is routinely administered in clinical practise. OBJECTIVES To assess the efficacy and safety of ketorolac for postoperative pain in children. SEARCH METHODS We searched the following databases, without language restrictions, to November 2017: CENTRAL (The Cochrane Library 2017, Issue 10); MEDLINE, Embase, and LILACS. We also checked clinical trials registers and reference lists of reviews, and retrieved articles for additional studies. SELECTION CRITERIA We included randomised controlled trials that compared the analgesic efficacy of ketorolac (in any dose, administered via any route) with placebo or another active treatment, in treating postoperative pain in participants zero to 18 years of age following any type of surgery. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We analyzed trials in two groups; ketorolac versus placebo, and ketorolac versus opioid. However, we performed limited pooled analyses. We assessed the overall quality of the evidence for each outcome using GRADE, and created a 'Summary of findings' table. MAIN RESULTS We included 13 studies, involving 920 randomised participants. There was considerable heterogeneity among study designs, including the comparator arms (placebo, opioid, another NSAID, or a different regimen of ketorolac), dosing regimens (routes and timing of administration, single versus multiple dose), outcome assessment methods, and types of surgery. Mean study population ages ranged from 356 days to 13.9 years. The majority of studies chose a dose of either 0.5 mg/kg (as a single or multiple dose regimen) or 1 mg/kg (single dose with 0.5 mg/kg for any subsequent doses). One study administered interventions intraoperatively; the remainder administered interventions postoperatively, often after the participant reported moderate to severe pain.There were insufficient data to perform meta-analysis for either of our primary outcomes: participants with at least 50% pain relief; or mean postoperative pain intensity. Four studies individually reported statistically significant reductions in pain intensity when comparing ketorolac with placebo, but the studies were small and had various risks of bias, primarily due to incomplete outcome data and small sample sizes.We found limited data available for the secondary outcomes of participants requiring rescue medication and opioid consumption. For the former, we saw no clear difference between ketorolac and placebo; 74 of 135 (55%) participants receiving ketorolac required rescue analgesia in the post-anaesthesia care unit (PACU) versus 81 of 127 (64%) receiving placebo (relative risk (RR) 0.85, 95% confidence interval (CI) 0.71 to 1.00, P = 0.05; 4 studies, 262 participants). For opioid consumption in the PACU, we saw no clear difference between ketorolac and placebo (P = 0.61). For the time period zero to four hours after administration of the interventions, participants receiving ketorolac received 1.58 mg less intravenous morphine equivalents than those receiving placebo (95% CI -2.58 mg to -0.57 mg, P = 0.002; 2 studies, 129 participants). However, we are uncertain whether ketorolac has an important effect on opioid consumption, as the data were sparse and the results were inconsistent. Only one study reported data for opioid consumption when comparing ketorolac with an opioid. There were no clear differences between the ketorolac and opioid group at any time point. There were no data assessing this outcome for the comparison of ketorolac with another NSAID.There were insufficient data to allow us to analyze overall adverse event or serious adverse event rates. Although the majority of serious adverse events reported in those receiving ketorolac involved bleeding, the number of events was too low to conclude that bleeding risk was increased in those receiving ketorolac perioperatively. There was not a statistically significant increase in event rates for any specific adverse event, either in pooled analysis or in single studies, when comparing ketorolac and placebo. When comparing ketorolac with opioids or other NSAIDs, there were too few data to make any conclusions regarding event rates. Lastly, withdrawals due to adverse events were vary rare in all groups, reflecting the acute nature of such studies.We assessed the quality of evidence for all outcomes for each comparison (placebo or active) as very low, due to issues with risk of bias in individual studies, imprecision, heterogeneity between studies, and low overall numbers of participants and events. AUTHORS' CONCLUSIONS Due to the lack of data for our primary outcomes, and the very low-quality evidence for secondary outcomes, the efficacy and safety of ketorolac in treating postoperative pain in children were both uncertain. The evidence was insufficient to support or reject its use.
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Postoperative effects on lower third molars of using mouthwashes with super-oxidized solution versus 0.2% chlorhexidine gel: A randomized double-blind trial.
Coello-Gómez, A, Navarro-Suárez, S, Diosdado-Cano, JM, Azcárate-Velazquez, F, Bargiela-Pérez, P, Serrera-Figallo, MA, Torres-Lagares, D, Gutiérrez-Pérez, JL
Medicina oral, patologia oral y cirugia bucal. 2018;(6):e716-e722
Abstract
BACKGROUND The main objective of the present study is to evaluate the effects and possible benefits with regard to the postoperative period of lower third molar extractions, comparing the intraalveolar application of a bioadhesive gel of 0.2% chlorhexidine (CHX) to the use of a mouthwash with a super-oxidized solution, (SOS) Dermacyn® Wound Care (Oculus Innovative Sciences lnc., California, USA). MATERIAL AND METHODS A randomized double-blind study was carried out in 20 patients with a split-mouth design, with a total of 40 extractions of symmetrically impacted bilateral lower third molars. Patients were divided into two groups, a control group (C = 20) and an experimental group (D = 20). Any infectious complications, wound healing, plaque accumulation in the stitches, and presence of trismus and inflammation were evaluated using the distance between different facial points, at three, eight, and fifteen days after extraction. Pain, swelling, and amount of analgesics taken were evaluated using the VAS scale throughout the 15 days following extraction. Tolerance to treatment was evaluated using a verbal scale. Results were statistically compared using the Student's t- and chi-squared tests. RESULTS No statistically significant differences were found between the two groups with regard to infectious complications, swelling, or wound healing. Use of analgesics and self-reported pain levels were slightly lower in the experimental group than in the control group during days 6 and 7 of the study (p < 0.05). The global treatment tolerance was satisfactory and similar in both groups. CONCLUSIONS Both CHX and SOS are effective at improving the postoperative period after extraction of lower third molars.
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Single-dose intravenous diclofenac for acute postoperative pain in adults.
McNicol, ED, Ferguson, MC, Schumann, R
The Cochrane database of systematic reviews. 2018;(8):CD012498
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BACKGROUND Postoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) reduces patient opioid requirements and, in turn, reduces the incidence and severity of opioid-induced adverse events (AEs). OBJECTIVES To assess the analgesic efficacy and adverse effects of single-dose intravenous diclofenac, compared with placebo or an active comparator, for moderate to severe postoperative pain in adults. SEARCH METHODS We searched the following databases without language restrictions: the Cochrane Central Register of Controlled Trials (Cochrane Register of Studies Online), MEDLINE, and Embase on 22 May 2018. We checked clinical trials registers and reference lists of retrieved articles for additional studies. SELECTION CRITERIA We included randomized trials that compared a single postoperative dose of intravenous diclofenac with placebo or another active treatment, for treating acute postoperative pain in adults following any surgery. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. Two review authors independently considered trials for review inclusion, assessed risk of bias, and extracted data.Our primary outcome was the number of participants in each arm achieving at least 50% pain relief over a four- and six-hour period.Our secondary outcomes were time to, and number of participants using rescue medication; withdrawals due to lack of efficacy, AEs, and for any cause; and number of participants experiencing any AE, serious AEs (SAEs), and NSAID-related AEs. We performed a post hoc analysis of opioid-related AEs, to enable indirect comparisons with other analyses of postoperative analgesics.For subgroup analysis, we planned to analyze different doses and formulations of parenteral diclofenac separately.We assessed the overall quality of the evidence for each outcome using GRADE and created two 'Summary of findings' tables. MAIN RESULTS We included eight studies, involving 1756 participants undergoing various surgeries (dental, mixed minor, abdominal, and orthopedic), with 20 to 175 participants receiving intravenous diclofenac in each study. Mean study population ages ranged from 24.5 years to 54.5 years. Intravenous diclofenac doses varied among and within studies, ranging from 3.75 mg to 75 mg. Five studies assessed newer formulations of parenteral diclofenac that could be administered as an undiluted intravenous bolus. Most studies had an unclear risk of bias for several domains and a high risk of bias due to small sample size. The overall quality of evidence for each outcome was generally low for reasons including unclear risk of bias in studies, imprecision, and low event numbers.Primary outcomeThree studies (277 participants) produced a number needed to treat for an additional beneficial outcome (NNTB) for at least 50% of maximum pain relief versus placebo of 2.4 (95% confidence interval (CI) 1.9 to 3.1) over four hours (low-quality evidence). Four studies (436 participants) produced an NNTB of 3.8 versus placebo (95% CI 2.9 to 5.9) over six hours (low-quality evidence). No studies provided data for the comparison of intravenous diclofenac with another NSAID over four hours. At six hours there was no difference between intravenous diclofenac and another NSAID (low-quality evidence).Secondary outcomesFor secondary efficacy outcomes, intravenous diclofenac was generally superior to placebo and similar to other NSAIDs.For time to rescue medication, comparison of intravenous diclofenac versus placebo demonstrated a median of 226 minutes for diclofenac versus 80 minutes for placebo (5 studies, 542 participants, low-quality evidence). There were insufficient data for pooled analysis for comparisons of diclofenac with another NSAID (very low-quality evidence).For the number of participants using rescue medication, two studies (235 participants) compared diclofenac with placebo. The number needed to treat to prevent one additional harmful event (NNTp) (here, the need for rescue medication) compared with placebo was 3.0 (2.2 to 4.5, low-quality evidence). The comparison of diclofenac with another NSAID included only one study (98 participants). The NNTp was 4.5 (2.5 to 33) for ketorolac versus diclofenac (very low-quality evidence).The numbers of participants withdrawing were generally low and inconsistently reported (very low-quality evidence). Participant withdrawals were: 6% (8/140) diclofenac versus 5% (7/128) placebo, and 9% (8/87) diclofenac versus 7% (6/82) another NSAID for lack of efficacy; 2% (4/211) diclofenac versus 0% (0/198) placebo, and 3% (4/138) diclofenac versus 2% (2/129) another NSAID due to AEs; and 11% (21/191) diclofenac versus 17% (30/179) placebo, and 18% (21/118) diclofenac versus 15% (17/111) another NSAID for any cause.Overall adverse event rates were similar between intravenous diclofenac and placebo (71% in both groups, 2 studies, 296 participants) and between intravenous diclofenac and another NSAID (55% and 58%, respectively, 2 studies, 265 participants) (low-quality evidence for both comparisons). Serious and specific AEs were rare, preventing meta-analysis.There were sufficient data for a dose-effect analysis for our primary outcome for only one alternative dose, 18.75 mg. Analysis of the highest dose employed in each study demonstrated a relative benefit compared with placebo of 1.9 (1.4 to 2.4), whereas for the group receiving 18.75 mg, the relative benefit versus placebo was 1.6 (1.2 to 2.1, 2 studies). Compared to another NSAID, the high-dose analysis demonstrated a relative benefit of 0.9 (0.8 to 1.1), for the group receiving 18.75 mg, the relative benefit was 0.78 (0.65 to 0.93). For direct comparison of high dose versus 18.75 mg, the proportion of participants with at least 50% pain relief was 66% (90/137) for the high-dose arm versus 57% (77/135) in the low-dose arm. There were insufficient data for subgroup meta-analysis of different diclofenac formulations. AUTHORS' CONCLUSIONS The amount and quality of evidence for the use of intravenous diclofenac as a treatment for postoperative pain is low. The available evidence indicates that postoperative intravenous diclofenac administration offers good pain relief for the majority of patients, but further research may impact this estimate. Adverse events appear to occur at a similar rate to other NSAIDs. Insufficient information is available to assess whether intravenous diclofenac has a different rate of bleeding, renal dysfunction, or cardiovascular events versus other NSAIDs. There was insufficient information to evaluate the efficacy and safety of newer versus traditional formulations of intravenous diclofenac. There was a lack of studies in major and cardiovascular surgeries and in elderly populations, which may be at increased risk for adverse events.
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Effects of the Preoperative Administration of Dexketoprofen Trometamol on Pain and Swelling After Implant Surgery: A Randomized, Double-Blind Controlled Trial.
Sánchez-Pérez, A, Muñoz-Peñalver, J, Moya-Villaescusa, MJ, Sánchez-Matás, C
The Journal of oral implantology. 2018;(2):122-129
Abstract
The fear of postoperative pain is often mentioned by patients as one of the factors that is most frequently associated with dental implants. To reduce this factor, a single oral dose of 25 mg dexketoprofen trometamol (DKT) or placebo was administered 15 minutes before implant surgery. One hundred patients who required single-implant treatments were randomly assigned to 1 of 2 blinded groups. The patients in the test group were given 25 mg DKT (DKT group), and those in the control group were given 500 mg vitamin C as a placebo (PLACEBO group). A subjective visual analogue scale of 100 mm in length was used to evaluate pain. Inflammation and complications were assessed using a 5-point Likert scale. An analysis of variance, t-tests, and a Mann-Whitney U test were performed. Among the 100 patients, 83 completed the study (there were 8 dropouts in the PLACEBO group and 9 in the DKT group). The patients who received DKT reported a lower pain intensity during the immediate postoperative period. The inflammatory response was weaker in the DKT group than the control group at 48 hours, but bleeding was greater. There were no other complications in either of the groups. In conclusion, the preemptive use of 25 mg soluble DKT administered orally 15 minutes before implant surgery can reduce the severity of immediate postoperative pain.
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Multi-Modal Pain Control in Ambulatory Hand Surgery.
Harrison, RK, DiMeo, T, Klinefelter, RD, Ruff, ME, Awan, HM
American journal of orthopedics (Belle Mead, N.J.). 2018;(6)
Abstract
We evaluated postoperative pain control and narcotic usage after thumb carpometacarpal (CMC) arthroplasty or open reduction and internal fixation (ORIF) of the distal radius in patients given opiates with or without other non-opiate medication using a specific dosing regimen. A prospective, randomized study of 79 patients undergoing elective CMC arthroplasty or ORIF of the distal radius evaluated postoperative pain in the first 5 postoperative days. Patients were divided into 4 groups: Group 1, oxycodone and acetaminophen PRN; Group 2, oxycodone and acetaminophen with specific dosing; Group 3, oxycodone, acetaminophen, and OxyContin with specific dosing; and Group 4, oxycodone, acetaminophen, and ketorolac with specific dosing. During the first 5 postoperative days, we recorded pain levels according to a numeric pain scale, opioid usage, and complications. Although differences in our data did not reach statistical significance, overall pain scores, opioid usage, and complication rates were less prevalent in the oxycodone, acetaminophen, and ketorolac group. Postoperative pain following ambulatory hand and wrist surgery under regional anesthesia was more effectively controlled with fewer complications using a combination of oxycodone, acetaminophen, and ketorolac with a specific dosing regimen.
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New Advances in Acute Postoperative Pain Management.
Mitra, S, Carlyle, D, Kodumudi, G, Kodumudi, V, Vadivelu, N
Current pain and headache reports. 2018;(5):35
Abstract
PURPOSE OF REVIEW Postoperative pain remains one of the most common challenges following inpatient and outpatient surgeries. With our advances in modern medicine, pain following surgical procedures still remains a challenge, though significant accomplishments have been made over the past few decades. This article highlights some of the promising new advances and approaches in postoperative pain management. RECENT FINDINGS Over the last decade, Enhanced Recovery after Surgery (ERAS) pathways and protocols are becoming the benchmark standards for enhancing postoperative recovery. Multimodal analgesia (MMA) is an essential component of such care. Further, in the wake of serious and persistent concern on the opioid epidemic in the USA, there has been a recent renewal of interest in non-opioid alternatives or adjuncts in controlling postoperative pain, often in the context of MMA. Intravenous (IV) acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), magnesium, ketamine, dexmedetomidine, liposomal bupivacaine, and newer neuraxial and peripheral regional techniques as well as patient-controlled modalities are gaining importance. Gabapentinoids have become popular but recent meta-analytic reviews have cast doubt on their routine use in perioperative settings. Among opioids, sublingual sufentanil, IV oxycodone, and iontophoretic transdermal fentanyl hold promise. Acupuncture and transcutaneous electrical nerve stimulation may be useful as adjuncts in MMA packages. Genetic testing, derivatives of herbal preparations, and an extended role of acute pain services may emerge as potential areas of importance in the future. There are, however, critical gaps in good quality evidence in many of the practice guideline recommendations. In the era of opioid epidemic, several lines of evidence have emerged to support non-opioid-based drugs and approaches along with a few newer opioid formulations for postoperative pain management, although more research is needed to find the right balance of efficacy and safety.
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Topical diltiazem ointment in post-hemorrhoidectomy pain relief: A meta-analysis of randomized controlled trials.
Huang, YJ, Chen, CY, Chen, RJ, Kang, YN, Wei, PL
Asian journal of surgery. 2018;(5):431-437
Abstract
BACKGROUND Hemorrhoidectomy is commonly associated with postoperative pain. Calcium channel blockers are known to cause relaxation of gastrointestinal smooth muscle and oral diltiazem has also been shown to reduce the resting anal pressure. OBJECTIVE We attempted to analyze efficacy and side effects of topical diltiazem oint. in post-operative pain control. METHODS This is a meta-analysis of patients who underwent hemorrhoidectomy using topical diltiazem oint. versus placebo (Vaseline) for pain control. Patients with third or fourth degree hemorrhoids undergoing traditional hemorrhoidectomy were included. Procedures took place in the colorectal division of a hospital in 5 countries. Five randomized control trials (RCTs) published between 2005 and 2016 including 227 patients were included our meta-analysis (Diltiazem (calcium channel block) group = 137; Placebo (Vaseline) group = 90). Pain assessment was performed using a standardized Visual Analogue Scale. Any side effects of surgery or medication use, which were noted by the patient or the surgeon, also were recorded. RESULTS A total of 227 patients were included in the meta-analysis. The results revealed that Diltiazem ointment was statistically significant in reducing pain within 48 h, at 72 h, and more than 96 h after operation compared to the placebo group. Regarding overall complications (including headache), there was no statistical significance between diltiazem and placebo group. CONCLUSIONS Topical application of diltiazem effectively relieves pain after hemorrhoidectomy with minimal side effects. Further large studies are needed to substantiate its value in clinical practice.
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Pre-Emptive Effect of Dexamethasone and Diclofenac Sodium Associated With Codeine on Pain, Swelling, and Trismus After Third Molar Surgery: A Split-Mouth, Randomized, Triple-Blind, Controlled Clinical Trial.
Lima, TC, Bagordakis, E, Falci, SGM, Dos Santos, CRR, Pinheiro, MLP
Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 2018;(1):60-66
Abstract
PURPOSE We aimed to compare the effect of dexamethasone, 8 mg, and diclofenac sodium, 50 mg, associated with codeine, 50 mg, on the control of pain, swelling, and trismus after extraction of impacted third molars. MATERIALS AND METHODS Fifteen healthy patients with a mean age of 22.8 years (SD, 12.62 years) received a single oral dose of either drug 1 hour before each surgical procedure (left and right teeth). At 24, 48, and 72 hours after surgery, swelling was determined by use of linear measurements on the face and trismus was determined by maximal mouth opening. Postoperative pain was self-recorded by the patients using a numerical rating scale at 24-hour intervals for a period of 72 hours. Data analysis involved descriptive statistics and Shapiro-Wilk, Wilcoxon, and paired t tests (P < .05). RESULTS Dexamethasone controlled pain (P = .016) and edema (P = .08) within 48 hours better than diclofenac sodium associated with codeine. No statistically significant differences were found between drugs regarding trismus and consumption of rescue analgesics (acetaminophen). CONCLUSIONS The results of this study suggest that pre-emptive administration of dexamethasone, 8 mg, showed better control of pain and swelling in bilateral extractions of third impacted mandibular molars.
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The effect of green tea ointment on episiotomy pain and wound healing in primiparous women: A randomized, double-blind, placebo-controlled clinical trial.
Shahrahmani, H, Kariman, N, Jannesari, S, Rafieian-Kopaei, M, Mirzaei, M, Ghalandari, S, Shahrahmani, N, Mardani, G
Phytotherapy research : PTR. 2018;(3):522-530
Abstract
The delayed healing of episiotomy wound and its associated pain is a major problem in obstetrics. Because green tea has analgesic and wound-healing properties, the present study was conducted to determine the effect of green tea ointment on episiotomy pain and wound-healing. The green tea extract was also standardized by measuring its Phenolic and flavonoid compounds, antioxidant activity, and one of its active components, that is, Epigallocatechin gallate. The present clinical trial was conducted on 99 primiparous women visiting Afzalipour Hospital in Kerman in 2015. The subjects were randomly divided into 3 groups, including a green tea ointment group, a placebo ointment group, and a routine care group. The 2 ointment groups smeared 2 cm of the green tea or placebo ointments onto their sutured area twice daily for a total of 10 days. The severity of pain was assessed in the subjects using the visual pain scale and wound-healing using the Redness, Edema, Ecchymosis, Discharge, Approximation (REEDA) scale before the intervention and on the 5th and 10th days after delivery. To standardize the extract, Epigallocatechin gallate was measured by high-performance liquid chromatography (HPLC). Phenolic and flavonoid compounds, as well as antioxidant activity of the extract were also determined by spectrometry methods. Before the intervention, no significant differences were observed between the 3 groups in terms of their personal and obstetric details (p > .05), the severity of pain (p = .118), and the REEDA score (p = .212). On the 5th and 10th days after delivery, the severity of pain was significantly lower in the green tea group than in the other 2 groups (p < .0001). The mean REEDA score on the 5th and 10th days showed a better and faster healing in the green tea group compared to the other 2 groups (p < .0001). Total content of phenolic and flavonoids contents of green tea were 74.2 mg/g Gallic acid equivalent and 16.3 mg/g Rutin equivalent, respectively, and its antioxidant capacity was 46% of b-carotene. Green tea ointment appears to be effective in relieving episiotomy pain and improving wound-healing in this study. Further studies are recommended to be conducted on the effectiveness and safety of the different doses of green tea ointment.