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1.  A clinical trial of long-acting local anesthetics for periodontal surgery. 
Anesthesia Progress  1990;37(4):194-198.
The efficacy of long-acting local anesthetics for anesthesia during periodontal surgery and for analgesia during the immediate postoperative period was evaluated. The rationale for using long-acting local anesthetics such as etidocaine and bupivacaine is that they can provide surgical anesthesia and, because of their long duration, prevent discomfort that may occur for 4-6 hours postoperatively. Two clinical trials were performed. The first enrolled patients requiring bilateral periodontal surgery. Using a matched pair design and double-blind randomized study conditions, 2% lidocaine 1/100,000 epinephrine was compared with 1.5% etidocaine 1/200,000 epinephrine for periodontal surgery. The time until complete recovery and the time until pain onset were found to be longer for the etidocaine surgeries. Postoperative pain appeared more severe, and the need for oral analgesics was greater for the lidocaine surgeries. Surgeons' rating of surgical bleeding was significantly greater for the etidocaine procedures. When matched bilateral surgeries were not available, a second double-blind randomized parallel trial was performed that compared 1.5% etidocaine 1/200,000 epinephrine to 0.5% bupivacaine 1/200,000 epinephrine. No significant differences were seen in the quality of anesthesia, degree of bleeding, or postoperative pain between these two long-acting anesthetics.
PMCID: PMC2148673  PMID: 2096742
2.  Infiltrated lidocaine 2% with epinephrine 1:80,000 causes more postoperative pain than lidocaine 2% after oral soft tissue surgery. 
Anesthesia Progress  1999;46(2):71-76.
A controlled, randomized, double-blind, within-patient, crossover study was made with 50 patients (28 women and 22 men) of mean age 47 years (range, 32-69 years) who were subjected to identical bilateral gingivectomies. On one occasion, lidocaine 2% was infiltrated as the local anesthetic. On the other occasion, lidocaine 2% with epinephrine 1:80,000 was given. Postoperative pain intensity was recorded by the patients on a 100-mm visual analogue scale every hour during an 11-hour observation period. The mean pain intensity was numerically higher after lidocaine 2% at 0 hours and 1 hour postoperatively. Then the mean pain intensity after lidocaine 2% was lower than that after lidocaine 2% with epinephrine 1:80,000 throughout the remaining observation period. The difference in pain intensity was statistically significant (P < .05) at 2, 4, 5, 6, and 7 hours after surgery. Mean sum (SEM) pain intensity over the 11-hour observation period was lower (P = .03) after lidocaine 2%, 66.5 (13.4) mm than after lidocaine 2% with epinephrine 1:80,000, 92.6 (15.4) mm. The study shows that high epinephrine concentration (1:80,000) increases the postoperative pain after dental soft tissue surgery with mild pain.
PMCID: PMC2148891  PMID: 10853568
3.  A double-blind randomized controlled trial showing the analgesic and anesthetic properties of lidocaine E to be equivalent to those of ropivicaine and bupivacaine in carpal tunnel release surgery 
In a three-phase trial, the anesthetic properties of lidocaine, bupivacaine and ropivicaine were compared in carpal tunnel release surgery. In phase I, two groups of 25 sequential patients were injected with either lidocaine plain 2% or lidocaine 2% with adrenaline 1:100,000 (E), as the local anesthetic for outpatient carpal tunnel release surgery. Subjective injection pain, postoperative pain at 2 h increments and the number of analgesic pills taken were recorded. During the first postoperative hours, outcome measures were superior in the lidocaine E group.
In phase II, a double-blind randomized design compared 42 patients injected with either lidocaine E or a combination of lidocaine E and bupivacaine. Postoperative pain scores and analgesic pills taken were compared using nonparametric statistical tests. During the first 4 h there was a slight benefit in the duration of the anesthetic and fewer pain pills were used in the bupivacaine group.
Phase III was a randomized double-blind comparison of ropivicaine and lidocaine E 2% in 72 patients. There was a slight decrease in pain scores and fewer analgesic pills required during the first 6 h in the ropivicaine group.
Lidocaine plain 2% provided significantly inferior analgesic and anesthetic properties compared with lidocaine E 2%, bupivacaine or ropivicaine. Sequential randomized comparisons between lidocaine E and bupivacaine and ropivicaine showed clinical equivalence. The present study showed lidocaine E 2% to be a satisfactory and comparatively cost-effective anesthetic for outpatient carpal tunnel surgery.
PMCID: PMC3822459  PMID: 24227926
Carpal tunnel surgery; Local anesthesia
4.  A Clinical Evaluation of the Analgesic Efficacy of Preoperative Administration of Ketorolac and Dexamethasone Following Surgical Removal of Third Molars 
Anesthesia Progress  1998;45(3):110-116.
The purpose of this study was to compare the postoperative analgesic efficacy of the presurgical intravenous administration of a steroid (dexamethasone), a nonsteroidal anti-inflammatory drug (ketorolac), and a combination of the two medications. These drugs were administrated preoperatively, and their analgesic effects were assessed following the removal of four third molars using intravenous sedation (Fentany/Midazolam) and local anesthetic (2% lidocaine with 1:100,000 epinephrine). Thirty-four patients were randomly assigned to one of four groups: Group I (control), saline; Group II, 30 mg ketorolac; Group III, 8 mg dexamethasone; and Group IV, 30 mg ketorolac + 8 mg dexamethasone. Pain was assessed with the Heft-Parker graphic pain rating scale; the initial survey was completed preoperatively. The teeth were surgically removed by one of four oral and maxillofacial surgeons. Following surgery and initial recovery, the patients completed the second survey and were then admitted for overnight observation. The patients completed the remaining pain rating scales at 2-hr intervals for 12 hr. The last survey was completed at discharge (24 hr postoperatively). A postoperative narcotic analgesic was provided upon request (Tylenol 3). Pain data were assessed using one-way analysis of variance and the Duncan multiple range test (α = 0.05). At all postoperative intervals, the greatest pain scores were recorded in the control group. Statistically significant differences in pain scores were found at the 4-, 6-, 8-, and 10-hr postoperative intervals. At the 2-hr postoperative interval, pain had increased in all groups, but no differences were found among the groups. At the 4- and 6-hr interval, pain levels in Group I were significantly greater than those in Group II and Group IV, with Group III and IV not significantly different from Group II. At 10 hr, pain levels in the saline group were significantly greater than those in all the other groups. At all intervals, the only significant differences detected were found between the control group and the experimental groups; no significant differences were found at any point among any of the experimental groups. The relationship between the number of doses of narcotic medication taken postoperatively, and the preoperative intravenous regimen was assessed with a Kruskal-Wallis test. No significant difference was found among groups with respect to the need for postoperative pain medication (P > 0.05). Postoperative analgesia following third molar surgery was enhanced in the first 10 hr with the preoperative administration of ketorolac. The addition of dexamethasone did not improve the analgesic effect.
PMCID: PMC2148954  PMID: 19598716
Analgesic efficacy; Pain control; Nonsteroidal anti-inflammatory drugs; Steroids
5.  Effect of pretreatment with ketorolac tromethamine on operative pain during periodontal surgery: A case-control study 
The efficacy of a nonsteroidal anti-inflammatory agent, ketorolac tromethamine, was evaluated in pain control after periodontal surgery. This type of agent acts peripherally by inhibiting the release of prostaglandins and minimizing the local inflammatory response. Thus, there may be an advantage in pretreatment administration of ketorolac tromethamine, 10 mg, compared with placebo on operative pain during periodontal surgery.
Materials and Methods:
Two groups of 40 outpatients from the Department of Periodontology, Darshan Dental College and Hospital, Udaipur, were selected for this study. Patients who were to undergo periodontal surgery were randomly given either one group 10 mg ketorolac immediately before surgery or the other group placebo tablets at least 30 minutes before administration of local anesthesia (LA). All procedures were performed under LA, and the total volume of anesthetic used was recorded. The duration of surgery from the time of incision to the placement of the last suture was recorded. At the completion of the surgery, patients were supplied with printed record forms and were asked to rate their subjective operative pain intensity using a visual analog scale.
Statistical analysis:
The data were analyzed using the student t test.
Results indicated that preoperative treatment with ketorolac significantly reduced initial pain intensity of operative pain as compared with placebo. No adverse reactions related to preoperative medication were observed.
The results of this study showed that 10-mg ketorolac administered immediately before periodontal surgery was effective for alleviating the operative painful sequelae.
PMCID: PMC3134049  PMID: 21772723
Ketorolac; operative pain; pain/prevention and control; periodontal surgery
6.  The comparison effects of intra-articular injection of different opioids on postoperative pain relieve after arthroscopic anterior cruciate ligament reconstruction: A randomized clinical trial study* 
Pain after knee surgery, if not relieved, it would lead to a more severe and prolonged pain that can delay the patients recovery and rehabilitation. The effect of pain relief by some drugs after intra-articular injection has been shown. This study compared the effect of intra-articular injection of opioids (morphine, pethidine, methadone, and tramadol) on postoperative relieving pain after arthroscopic anterior cruciate ligament (ACL) reconstruction.
150 candidate patients for knee arthroscopic ACL reconstruction were randomly enrolled into five groups. At the end of the procedure, all patients in each group received a joint injection solution including 9.5 millimeters bupivacaine with 1:200,000 epinephrine. The remaining 0.5 milliliters of syringe capacity was filled with one of the five solutions listed below: methadone group I: 5 mg methadone, morphine group II: 5 mg morphine, pethidine group III: 37.5 mg pethidine, tramadol group IV: 100 mg Tramadol, and control group V: 0.5 ml normal saline. Afterwards, any drug further administered to the patients based on need was recorded, and the morphine equivalent for all drugs was calculated. Patients need to narcotic drugs during the first twelve hours of hospitalization and pain scores were recorded. After data gathering, they were analyzed by SPSS 16 software with chi-Square, Kruskal-Wallis and ANOVA statistical tests.
The highest and the lowest significant pain intensity were seen in placebo and morphine groups, respectively, in the first, second and third 4 hours after surgery. There were significant differences among the groups for need to analgesics. In other words, placebo group needed the highest dosage of analgesics and morphine and methadone groups needed the lowest dosage of analgesics. Morphine and methadone groups had maximum and minimum response to pain, respectively, in the first, second and third 4 hours after surgery.
Administering 5 mg intra-articular morphine after arthroscopic ACL reconstruction is a valuable choice and is recommended to be added to other local anesthetics administrated drugs after this procedure.
PMCID: PMC3430042  PMID: 22973386
Knee Arthroscopic; Morphine; Pethidine; Methadone; Tramadol; Intra-Articular Injection
7.  Comparison of Bupivacaine and Lidocaine Use for Postoperative Pain Control in Endodontics 
Iranian Endodontic Journal  2010;5(1):31-35.
INTRODUCTION: Many patients suffer from mild, moderate or severe pain during or after root canal therapy. Theoretically, post-operative pain control can be achieved by using long-acting local anesthetics. The aim of this study was to evaluate the efficacy of a long acting anesthesia, bupivacaine, on preventing post-operative pain associated with endodontic treatment, and to compare it with lidocaine.
MATERIALS AND METHODS: This study was a double blind and randomized clinical trial on 30 patients' anterior maxillary teeth. The patients were divided into two groups of fifteen. One group was administered lidocanine (2% with 1:100000 epinephrine) local anesthesia and the other group was given bupivacaine (0.5% without epinephrine). The pain in patients were compared using the visual analogue scale (VAS) at definite times i.e. before treatment, during treatment and 2,4,6,8,10,12,24,36 and 48 hours after operation. Data were analyzed using One-way ANOVA tests.
RESULTS: Bupivacaine significantly decreased postoperative pain compared to lidocaine. Postoperative pain was directly related to preoperative pain. Women reported more pain, though significant difference in postoperative pain report was not found between different ages.
CONCLUSION: In conclusion, a single dose of bupivacaine 0.5% used in infiltration anesthesia could be more effective in reduction or prevention of post-operative endodontic pain compared with lidocaine.
PMCID: PMC4000677  PMID: 24778680
Bupivacaine; Infiltration; Lidocaine; Maxilla; Pain
8.  Comparative analysis of tissue reactions to anesthetic solutions: histological analysis in subcutaneous tissue of rats. 
Anesthesia Progress  2003;50(4):169-180.
Postanesthetic pain is a relatively common complication after local anesthesia. This complication may be caused by the anesthetic technique or by the anesthetic solution used. Tissue reactions induced by the anesthetic solutions may be one of the factors resulting in pain after anesthesia. The objective of this study was to comparatively analyze tissue reactions induced by different anesthetic solutions in the subcutaneous tissue of rats. The following solutions were utilized: 2% lidocaine without vasoconstrictor; a 0.5% bupivacaine solution with 1:200,000 adrenaline; a 4% articaine solution and 2% mepivacaine, both with 1:100,000 adrenaline; and a 0.9% sodium chloride solution as a control. Sterilized absorbent paper cones packed inside polyethylene tubes were soaked in the solutions and implanted in the subcutaneous region. The sacrifice periods were 1, 2, 5, and 10 days after surgery. The specimens were prepared and stained with hematoxylin and eosin for histological analysis. The results showed that there is a difference in tissue irritability produced by the local anesthetic solutions. The results also showed that there is no relation between the concentration of the drug and the inflammatory intensity, that the mepivacaine and articaine solutions promoted less inflammatory reaction than the bupivacaine, and that the lidocaine solution produced the least intense inflammation.
PMCID: PMC2007452  PMID: 14959905
9.  Comparison of preemptive analgesic effects of a single dose of nonopioid analgesics for pain management after ambulatory surgery: A prospective, randomized, single-blind studyin Turkish patients 
Preemptive analgesia used for postsurgical pain management has been shown to reduce the requirements of postoperative analgesics.
The aim of this study was to compare the preemptive analgesic effects of diflunisal, naproxen sodium, meloxicam, acetaminophen, and rofecoxin (no longer available in some markets) in patients undergoing ambulatory dental surgery and the need for postoperative pain management in these patients.
This prospective, randomized, single-blind study was conducted at the Departments of Anesthesiology and Reanimation and Oral and Maxillofacial Surgery, Baskent University, Adana Teaching and Medical Research Center, Adana, Turkey. Turkish outpatients aged ≥ 16 years with American Society of Anesthesiologists physical status 1 (ie, healthy) and scheduled to undergo surgical extraction of an impacted third molar were enrolled. Patients were randomly assigned to receive diflunisal 500 mg, naproxen sodium 550 mg, meloxicam 7.5 mg, acetaminophen 500 mg, or rofecoxib 12.5 mg. All medications were administered orally 1 hour before surgery as preemptive analgesia and after surgery if needed, up to the maximum recommended dose. Surgery was performed with the patient under local anesthesia (articaine hydrochloride). Pain intensity was assessed using a 100-mm visual analog scale (VAS) (0 = none to 100 = worst possible pain) at 2, 4, 6, and 12 hours after ambulatory surgery. The use of additional analgesics was recorded for 24 hours using patient diaries. Postoperative adverse events were recorded using the diaries.
One hundred fifty patients (108 women, 42 men; mean [SE] age, 26.8 [0.6] years; 30 patients per group) had data available for analysis. Demographic data were similar between the 5 groups. No significant differences in mean VAS scores were found between the 5 groups at any time point. All mean VAS scores indicated minor pain. The rate of additional postoperative analgesics required was significantly lower in the diflunisal group compared with groups receiving naproxen sodium, meloxicam, acetaminophen, and rofecoxib (3 [10%] patients vs 11 [37%], 15 [50%], 15 [50%], and 14 [47%] patients, respectively; all, P < 0.05). Bleeding at the surgical site was reported in 2 patients each in the diflunisal, naproxen sodium, meloxicam, and acetaminophen groups, and in 1 patient in the rofecoxib group; the between-group differences were not significant. No significant differences in the prevalences of other adverse effects (eg, nausea, vomiting, allergy, gastrointestinal symptoms) were found between the 5 treatment groups.
In the present study in patients undergoing third molar extraction, adequate preemptive analgesia, based on VAS scores, was found with all of the nonopioid analgesic agents used. Fewer patients required rescue medication with diflunisal. All 5 study drugs were similarly well tolerated.
PMCID: PMC3966011  PMID: 24678075
preemptive analgesia; ambulatory surgery; NSAIDs
10.  A Prospective, Randomized, Double-Blind Comparison of 2% Mepivacaine With 1 : 20,000 Levonordefrin Versus 2% Lidocaine With 1 : 100,000 Epinephrine for Maxillary Infiltrations 
Anesthesia Progress  2010;57(4):139-144.
The purpose of this prospective, randomized, double-blind crossover study was to compare the anesthetic efficacy of 2% mepivacaine with 1 : 20,000 levonordefrin versus 2% lidocaine with 1 : 100,000 epinephrine in maxillary central incisors and first molars. Sixty subjects randomly received, in a double-blind manner, maxillary central incisor and first molar infiltrations of 1.8 mL of 2% mepivacaine with 1 : 20,000 levonordefrin and 1.8 mL of 2% lidocaine with 1 : 100,000 epinephrine at 2 separate appointments spaced at least 1 week apart. The teeth were electric pulp tested in 2-minute cycles for a total of 60 minutes. Anesthetic success (obtaining 2 consecutive 80 readings with the electric pulp tester within 10 minutes) was not significantly different between 2% mepivacaine with 1 : 20,000 levonordefrin and 2% lidocaine with 1 : 100,000 epinephrine for the central incisor and first molar. However, neither anesthetic agent provided an hour of pulpal anesthesia.
PMCID: PMC3006661  PMID: 21174567
Lidocaine; Epinephrine; Mepivacaine; Levonordefrin; Infiltration; Maxillary
11.  Pain and swelling after periapical surgery related to the hemostatic agent used: Anesthetic solution with vasoconstrictor or aluminum chloride 
Objective: To assess pain and swelling in the first 7 days after periapical surgery and their relationship with the agent used for bleeding control. Study Design: A prospective study was conducted between October 2006 and March 2009. Patients subjected to root surgery, who completed the questionnaire and who consented to the postoperative instructions were included in the study. The subjects were divided into two groups according to the hemostatic agent used: A) gauze impregnated with anesthetic solution with vasoconstrictor; or B) aluminum chloride. The patients were administered a questionnaire, and were asked to record the severity of their pain and swelling on a plain horizontal visual analog scale (VAS). Data were recorded by the patients on the first 7 postoperative days. In addition, the patients were asked to record analgesic consumption. Results: A total of 76 questionnaires (34 in group A and 42 in group B) were taken to be correctly completed. Pain was reported to be most intense two hours after surgery. At this point 52.6% of the patients had no pain. Seventy-five percent of the patients consumed analgesics in the first 24 hours. There were no significant differences between the two groups in terms of the intensity of pain or in the consumption of analgesics. Swelling reached its maximum peak on the second day; at this point, 60.6% of the patients suffered mild or moderate swelling. The Expasyl™ group showed significantly greater swelling than the gauzes group. Conclusion: The type of hemostatic agent used did not influence either the degree of pain or the need for analgesia among the patients in this study. However, the patients belonging to the Expasyl™ group suffered greater swelling than the patients treated with gauzes impregnated with anesthetic solution with vasoconstrictor.
Key words:Hemostasis, periradicular surgery, aluminum chloride, pain, swelling.
PMCID: PMC3476021  PMID: 22322510
12.  Effects of Adding Ketamine to Fentanyl Plus Acetaminophen on Postoperative Pain by Patient Controlled Analgesia in Abdominal Surgery 
Postoperative pain is one of the most important complications encountered after surgery. A number of options are available for treating pain following surgery. One of those options is the use of intravenous patient-controlled analgesia (PCA). Ketamine is an anesthetic drug relieving pain with its NMDA receptor antagonistic effect.
This study is aiming at better pain management after abdominal surgery; the effects of adding ketamine to intravenous fentanyl plus acetaminophen PCA were evaluated.
Patients and Methods:
In a double-blind randomized clinical trial 100 patients, ASA I or II, 20 - 60 years old were divided into two groups. These patients were abdominal surgery candidates. In order to control postoperative pain in the control group an IV patient-control analgesia (PCA) containing fentanyl 10 μg/mL plus acetaminophen 10 mg/mL was instructed to be used for the patients, but the patients in ketamine group received ketamine 0.5 mg/mL plus control group PCA content. During the first 48 hours after surgery, ketamine patients were evaluated every 8 hours (at rest, while moving and coughing) to determine their pain scores using VAS scale, sedation score, additional analgesics, nausea and vomiting.
There were no significant demographic differences between two groups. Pain scores (at rest, while moving and coughing) during the first 48 hours were not significantly different between two groups (P values = 0.361, 0.367 and 0.204, respectively). Nausea scores were significantly lower in the ketamine group (P = 0.026).
The addition of ketamine to intravenous fentanyl plus acetaminophen PCA had not extra effects in relieving post abdominal surgery pain.
PMCID: PMC3961015  PMID: 24660145
Ketamine; Acetaminophen; Fentanyl; Postoperative; Pain; Abdomen; Surgical Abdomen
13.  Prospective, randomized, open-label, pilot clinical trial comparing the effects of dexamethasone coadministered with diclofenac potassium or acetaminophen and diclofenac potassium monotherapy after third-molar extraction in adults 
Patients who experience pain, swelling, and trismus after third-molar extraction are reported to experience a 3-fold higher rate of adverse effects (AEs) on quality of life compared with those who are asymptomatic after this surgery. Therefore, investigators emphasize the necessity for better control of this triad of sequelae. Steroids can reduce the risk for physiologic processes of inflammation, thereby suppressing the development of inflammation.
The aim of this study was to compare the effects of dexamethasone 8 mg IM and diclofenac potassium (K) 50 mg PO, dexamethasone 8 mg IM and acetaminophen 1000 mg PO, and monotherapy with diclofenac K 50 mg PO on postoperative pain, swelling, and trismus after surgical removal of third molars.
This prospective, randomized, open-label pilot study was conducted at the Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Lagos, Nigeria. Patients were randomly allocated to 1 of 3 treatment groups: concomitant treatment with dexamethasone 8 mg IM and diclofenac K 50 mg PO or acetaminophen 1000 mg PO, or monotherapy with diclofenac K 50 mg PO. Overall analgesic efficacy of the drug combinations was assessed for 7 days postoperatively using a 4-point categorical pain-intensity rating scale (0 = no pain; 1 = mild pain; 2 = moderate pain; and 3 = severe pain). Facial swelling was measured in 1 dimension on days 1, 2, and 7 after surgery using a tape measure placed from the tip of the tragus, to gonion, to the tip of the contralateral tragus, and trismus was assessed using interincisal mouth-opening ability, measured using a vernier-calibrated caliper on postoperative days 1, 2, and 7. Tolerability was assessed using direct questioning of the patients at follow-up visits.
A total of 150 patients (50 per treatment group) were included in the analysis (76 women, 74 men; mean [SD] age, 26.8 [5.04] years [range, 18–45 years]; 100% Nigerian). The proportion of patients reporting no pain on the pain-intensity rating scale was significantly higher in the group receiving dexamethasone and diclofenac K compared with that in the groups receiving dexamethasone and acetaminophen or diclofenac K monotherapy (44% vs 22% and 24%, respectively; both, P < 0.05). Facial swelling was significantly less with dexamethasone and diclofenac K or dexamethasone and acetaminophen compared with diclofenac K alone (day 1: P = 0.013 and P = 0.011, respectively; day 2: P = 0.002 and P = 0.004, respectively). However, trismus relief was statistically similar between the 3 treatment groups on postoperative days 1 and 2. No AEs or complications were recorded.
In this open-label pilot study, concomitant treatment with dexamethasone and diclofenac K provided significant relief of postsurgical pain and swelling compared with dexamethasone and acetaminophen or monotherapy with diclofenac K after third-molar extraction in these patients.
PMCID: PMC3965982  PMID: 24678099
dexamethasone; diclofenac potassium; acetaminophen; third-molar extraction
14.  Preoperative Intravenous Tramadol Versus Diclofenac for Preventing Postoperative Pain After Third Molar Surgery: A Comparative Study 
The purpose of this study was to compare the analgesic efficacy of a single-dose of preoperative intravenous tramadol versus diclofenac in preventing pain after third molar surgery.
Materials and Methods
Fifty patients undergoing elective third molar surgery were randomly assigned into one of the two groups (25 in each group): Group 1 received diclofenac 75 mg, and Group 2 received tramadol 50 mg intravenously preoperatively before the surgery. After injection of the study drugs, the impacted third molars were removed under local anesthetic agent.
The difference in postoperative pain was assessed by four primary end-points: pain intensity as measured by a 100 mm visual analogue scale hourly for 12 h, median time to rescue analgesic, postoperative acetaminophen consumption, and patient’s global assessment. Throughout the 12 h investigation period, patients reported significantly lower pain intensity scores in the diclofenac versus tramadol group (P = 0.0001, Mann–Whitney U-test). Patients also reported significantly longer median time to rescue analgesic (10 vs. 8 h, P < 0.05, Student t test), lesser postoperative acetaminophen consumption (P < 0.05, Student t test) for the diclofenac versus tramadol group.
Preoperative intravenous diclofenac 75 mg is more effective than tramadol 50 mg in the prevention of postoperative dental pain.
PMCID: PMC3267914  PMID: 23204745
Preemptive analgesia; Diclofenac; Tramadol
15.  The Effect of Diclofenac Mouthwash on Periodontal Postoperative Pain 
Dental Research Journal  2011;8(3):146-149.
The need to relieve pain and inflammation after periodontal surgery and the side effects of systemic drugs and advantages of topical drugs, made us to evaluate the effect of Diclofenac mouthwash on periodontal postoperative pain.
In this double-blind, randomized clinical trial study 20 quadrants of 10 patients(n = 20) aged between 22-54 who also acted as their own controls, were treated using Modified Widman Flap procedure in two quadrants of the same jaw with one month interval between the operations.
After the operation in addition to ibuprofen 400 mg, one quadrant randomly received Diclofenac mouthwash (0/01%) for 30 seconds, 4 times a day (for a week) and for the contrary quadrant, ibuprofen and placebo mouthwash was given to be used in the same manner. The patients scored the number of ibuprofen consumption and their pain intensity based on VAS index in a questionnaire in days 1, 2, 3 and the first week after operation. The findings were analysed using two-way ANOVA, t-test and Wilcoxon. P-value less than 0.05 considered to be significant.
There was a significant difference between the mean values of pain intensity of two quadrants in four periods (P = 0.031). But, there was no significant difference between the average ibuprofen consumption in two groups (P = 0.51). Postoperative satisfaction was not significantly different in two quadrants (P = 0.059). 60% of patients preferred Diclofenac mouthwash.
Diclofenac mouthwash was effective in reducing postoperative periodontal pain but it seems that it isn’t enough to control postoperative pain on its own.
PMCID: PMC3177390  PMID: 22013478
Diclofenac; Mouthwash; Pain; Pain measurement
16.  Effectiveness and tolerability of once-daily nimesulide versus ibuprofen in pain management after surgical extraction of an impacted third molar: A 24-hour, double-blind, randomized, double-dummy, parallel-group study 
Nimesulide is a nonsteroidal, anti-inflammatory drug that hasbeen used for a wide range of acute and chronic pain. A once-daily formulation of nimesulide is now commercially available, but its effectiveness in pain management after dental surgery has not been assessed.
The aim of this study was to assess the analgesic effectiveness and tolerability of oral treatment with once-daily nimesulide versus ibuprofen q6h over 24 hours in patients with postoperative pain associated with surgical extraction of an impacted third molar.
This 24-hour, double-blind, randomized, double-dummy, parallel-groupstudy was conducted at a private practice in Caracas, Venezuela. Patients aged between 12 and 60 years with moderate to severe pain after extraction of an impacted third molar were enrolled. Patients were randomized to receive a single dose of nimesulide (300-mg tablet) or ibuprofen (400-mg tablets) q6h for 24 hours. For double-dummy design, patients in the nimesulide group also received ibuprofen placebo tablets, to be taken q6h for 24 hours, and patients in the ibuprofen group received a nimesulide placebo tablet. The primary end points were pain intensity (PI) and pain relief scores over 24 hours. Secondary end points included total pain relief, PI difference (PID), sum of PID (SPID), time to first measurable change in PI (ie, PID ≥ 10 mm), and use of rescue medication (acetaminophen). Patients also rated the treatment's effectiveness as very poor to very good on questioning by the study investigator. Spontaneously reported adverse effects (AEs) were recorded.
Eighty-six patients were enrolled (56 females, 30 males), with 43 patientsper treatment group (mean age: nimesulide group, 25.2 years; ibuprofen group, 24.2 years). The baseline characteristics were statistically similar between the 2 groups. Compared with baseline, mean PI scores were significantly lower in both treatment groups at all time points throughout the study (P < 0.001). Mean PI scores were significantly lower in the nimesulide group compared with the ibuprofen group at 15 and 45 minutes and 1 hour after study drug administration (P ≤ 0.049). Time to first measurable change in PI was within the first 15 minutes in 22 patients (52%) in the nimesulide group and in 14 patients (33%) in the ibuprofen group (P = 0.03). Analgesia lasted 24 hours with nimesulide and ibuprofen (PI scores at 24 hours, 9.4 and 3.6, respectively). The mean PR score was significantly lower in the nimesulide group compared with the ibuprofen group at 1 hour after study drug administration (P = 0.049). Compared with baseline, PID and SPID were significantly higher in both treatment groups throughout the study (P < 0.001). Significantly more patients in the nimesulide group than in the ibuprofen group reported that treatment provided effective pain relief (82% vs 73%; P = 0.013). No AEs were reported in either treatment group throughout the study. Use of rescue medication was statistically similar between the nimesulide and ibuprofen groups (38% and 31%, respectively).
In this study of patients with moderate to severe pain afterextraction of impacted third molars, nimesulide and ibuprofen provided effective 24-hour relief. However, the results suggest that the analgesic effect of nimesulide had a faster onset (<15 minutes) and was stronger (based on patient opinion) than that of ibuprofen. Both study drugs were well tolerated.
PMCID: PMC3964531  PMID: 24672121
nimesulide; ibuprofen; dental pain; programmed liberation
17.  Evaluation of prilocaine for the reduction of pain associated with transmucosal anesthetic administration. 
Anesthesia Progress  1999;46(2):52-55.
This investigation evaluated the use and efficacy of prilocaine HCl (4% plain Citanest) for minimizing pain associated with the intraoral administration of local anesthesia. Clinical anecdotes support the hypothesis that prilocaine without a vasoconstrictor reduces pain during injection. To determine relative injection discomfort, use of 4% plain prilocaine was compared with use of 2% lidocaine with 1:100,000 epinephrine and 2% mepivacaine with 1:20,000 levonordefrin. Prior to routine endodontic procedures, 150 adult patients received 0.3 to 1.8 mL of local anesthetic via the same gauge needle without the use of a topical local anesthetic. Injection methods included buccal infiltration, labial infiltration, palatal infiltration, and inferior alveolar nerve block. Following each injection, patients were asked to describe the level of discomfort by scoring on a visual analog scale of 1 to 10, where 1 = painless and 10 = severe pain. Analyses via 2-way analysis of variance revealed no interaction between anesthetic and site of injection. However, there were statistically significant differences among the injection sites. Post hoc analysis revealed that prilocaine was associated with significantly less pain perception when compared to mepivacaine and lidocaine. These results suggest that differences in initial pain perception during transmucosal injection may be a function of the local anesthetic use, and prilocaine can produce less discomfort than the others tested.
PMCID: PMC2148897  PMID: 10853565
18.  Bilateral Brachial Plexus Home Going Catheters After Digital Amputation for Patient With Upper Extremity Digital Gangrene 
Peripheral nerve catheter placement is used to control surgical pain. Performing bilateral brachial plexus block with catheters is not frequently performed; and in our case sending patient home with bilateral brachial plexus catheters has not been reported up to our knowledge. Our patient is a 57 years old male patient presented with bilateral upper extremity digital gangrene on digits 2 through 4 on both sides with no thumb involvement. The plan was to do the surgery under sequential axillary blocks. On the day of surgery a right axillary brachial plexus block was performed under ultrasound guidance using 20 ml of 0.75% ropivacaine. Patient was taken to the OR and the right fingers amputation was carried out under mild sedation without problems. Left axillary brachial plexus block was then done as the surgeon was closing the right side, two hours after the first block was performed. The left axillary block was done also under ultrasound using 20 ml of 2% mepivacaine. The brachial plexus blocks were performed in a sequential manner. Surgery was unremarkable, and patient was transferred to post anesthetic care unit in stable condition. Over that first postoperative night, the patient complained of severe pain at the surgical sites with minimal pain relief with parentral opioids. We placed bilateral brachial plexus catheters (right axillary and left infra-clavicular brachial plexus catheters). Ropivacaine 0.2% infusion was started at 7 ml per hour basal rate only with no boluses on each side. The patient was discharged home with the catheters in place after receiving the appropriate education. On discharge both catheters were connected to a single ON-Q (I-flow Corporation, Lake Forest, CA) ball pump with a 750 ml reservoir using a Y connection and were set to deliver a fixed rate of 7 ml for each catheter. The brachial plexus catheters were removed by the patient on day 5 after surgery without any difficulty. Patient's postoperative course was otherwise unremarkable. We concluded that home going catheters are very effective in pain control postoperatively and they shorten the period of hospital stay.
Brachial plexus; Home going catheters; Post-operative pain
PMCID: PMC3279478  PMID: 22393345
19.  The Role of Different Anesthetic Techniques in Altering the Stress Response During Cardiac Surgery in Children: A Prospective, Double-Blinded, and Randomized Study 
Our goal was to evaluate the role of three anesthetic techniques in altering the stress response in children undergoing surgery for repair of congenital heart diseases utilizing cardiopulmonary bypass in the setting of fast tracking or early tracheal extubation. Furthermore, we wanted to evaluate the correlation between blunting the stress response and the perioperative clinical outcomes.
Prospective, randomized, double-blinded study.
Single center from December 2008 to May of 2011.
Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied between ages 30 days to 3 years old who were scheduled to undergo repair for a ventricular septal defect, atrioventricular septal defect, or Tetralogy of Fallot.
Children undergoing surgical repair of congenital heart disease were randomized to receive low-dose fentanyl (10 mcg/kg; low-dose fentanyl), high-dose fentanyl (25mcg/kg; high-dose fentanyl), or low-dose fentanyl plus dexmedetomidine (as a 1 mcg/kg loading dose followed by infusion at 0.5mcg/kg/hr until separation from cardiopulmonary bypass. In addition, patients received a volatile anesthetic agent as needed to maintain hemodynamic stability. Blood samples were tested for metabolic, hormonal and cytokine markers at baseline, after sternotomy, after the start of cardiopulmonary bypass, at the end of the procedure and at 24 hours postoperatively.
Measurements and Main Results
Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied. Subjects in the low-dose fentanyl plus placebo group had significantly higher levels of adrenocorticotropic hormone, cortisol, glucose, lactate, and epinephrine during the study period. The lowest levels of stress markers were seen in the high-dose fentanyl plus placebo group both over time (adrenocorticotropic hormone, p = 0.01; glucose, p = 0.007) and at individual time points (cortisol and lactate at the end of surgery, epinephrine poststernotomy; p < 0.05). Subjects in the low-dose fentanyl plus dexmedetomidine group had lower lactate levels at the end of surgery compared with the low-dose fentanyl plus placebo group (p < 0.05). Although there were no statistically significant differences in plasma cytokine levels between the three groups, the low-dose fentanyl plus placebo group had significantly higher interleukin-6:interleukin-10 ratio at 24 hours postoperatively (p < 0.0001). In addition, when compared with the low-dose fentanyl plus placebo group, the low-dose fentanyl plus dexmedetomidine group showed lower norepinephrine level from baseline at poststernotomy, after start of cardiopulmonary bypass, and end of surgery (p ≤ 0.05). Subjects in the low-dose fentanyl plus placebo group had more postoperative narcotic requirement (p = 0.004), higher prothrombin time (p ≤ 0.03), and more postoperative chest tube output (p < 0.05). Success of fast tracking was not significantly different between groups (low-dose fentanyl plus placebo 75%, high-dose fentanyl plus placebo 82%, low-dose fentanyl plus dexmedetomidine 93%; p = 0.39).
The use of low-dose fentanyl was associated with the greatest stress response, most coagulopathy, and highest transfusion requirement among our cohorts. Higher dose fentanyl demonstrated more favorable blunting of the stress response. When compared with low-dose fentanyl alone, the addition of dexmedetomidine improved the blunting of the stress response, while achieving better postoperative pain control.
PMCID: PMC3885862  PMID: 23644384
cytokines; early extubation after pediatric cardiac surgery; pediatric cardiac surgery; stress response after cardiopulmonary bypass
20.  Effect of intraoperative lidocaine on anesthetic consumption, and bowel function, pain intensity, analgesic consumption and hospital stay after breast surgery 
Korean Journal of Anesthesiology  2012;62(5):429-434.
Perioperative lidocaine infusion improves postoperative outcomes, mostly after abdominal and urologic surgeries. Knowledge of the effect of lidocaine on peripheral surgeries is limited. Presently, we investigated whether intraoperative lidocaine infusion reduced anesthetic consumption, duration of ileus, pain intensity, analgesic consumption and hospital stay after breast plastic surgeries.
Sixty female patients, aged 20-60 years, enrolled in this prospective study were randomly and equally divided to two groups. One group (n = 30) received a 1.5 mg/kg bolus of lidocaine approximately 30 min before incision followed by continuous infusion of lidocaine (1.5 mg/kg/h) until skin closure (lidocaine group). The other group (n = 30) was untreated (control group). Balanced inhalation (sevoflurane) anesthesia and multimodal postoperative analgesia were standardized. End tidal sevoflurane concentration during surgery, time to the first flatus and defecation, visual analog pain scale (0-10), analgesic consumption and associated side effects at 24, 48, and 72 h after surgery, hospital stay, and patient's general satisfaction were assessed.
Compared to the control group, intraoperative lidocaine infusion reduced by 5% the amount of sevoflurane required at similar bispectral index (P = 0.014). However, there were no significant effects of lidocaine regarding the return of bowel function, postoperative pain intensity, analgesic sparing and side effects at all time points, hospital stay, and level of patient's satisfaction for pain control.
Low dose intraoperative lidocaine infusion offered no beneficial effects on return of bowel function, opioid sparing, pain intensity and hospital stay after various breast plastic surgeries.
PMCID: PMC3366309  PMID: 22679539
Analgesic consumption; Anesthetic consumption; Bowel function; Hospital stay; Intravenous lidocaine; Pain score
21.  Effect of long acting local anesthetic on postoperative pain in teeth with irreversible pulpitis: Randomized clinical trial 
The objective of this study was to compare the effect of long acting anesthetics on postoperative pain in teeth with irreversible pulpitis.
Forty patients were randomly assigned into two groups of twenty patients each. Each patient who fit the inclusion criteria was administered local anesthesia before undergoing root canal treatment. The anesthetic solution was either 2% lidocaine with 1:80,000 epinephrine or 0.5% bupivacaine with 1:200,000 epinephrine. Patients were instructed to complete a VAS pain score at 6, 12, 24 h after single visit root canal treatment. Data were analyzed by Mann–Whitney, Cochrane Q analysis and t test to compare qualitative and quantitative data between the groups.
The results showed the levels of pain of the patients who received lidocaine as the anesthetic agent and had significantly more postoperative pain after root canal treatment (P < 0.05) but had significantly decreased pain by 24 h compared to the bupivacaine group patients who had significantly lower postoperative pain levels at 6 and 12 h.
The use of long acting local anesthetic can significantly reduce the postoperative pain in teeth with irreversible pulpitis.
PMCID: PMC3909752  PMID: 24493972
Local Anesthetic; Irreversible Pulpitis; Postoperative Pain; Lidocaine; Bupivacaine
22.  Comparison of injection pain, heart rate increase, and postinjection pain of articaine and lidocaine in a primary intraligamentary injection administered with a computer-controlled local anesthetic delivery system. 
Anesthesia Progress  2004;51(4):126-133.
The purpose of this prospective, randomized, double-blind study was to compare the pain of injection, heart rate increase, and postinjection pain of the intraligamentary injection of 4% articaine with 1:100,000 epinephrine and 2% lidocaine with 1:100,000 epinephrine administered with a computer-controlled local anesthetic delivery system. Using a crossover design, intraligamentary injections of 1.4 mL of 4% articaine with 1:100,000 epinephrine and 1.4 mL of 2% lidocaine with 1:100,000 epinephrine were randomly administered on the mesial and distal aspects of the mandibular first molar with a computer-controlled local anesthetic delivery system in a double-blind manner at 2 separate appointments to 51 subjects. The results demonstrated the incidence of moderate pain was 14%-27% with needle insertion, with 0%-4% reporting severe pain. For solution deposition, moderate pain was reported 8%-18% of the time, with no reports of severe pain. There were no significant differences between the articaine and lidocaine solutions. Regarding heart rate changes, neither anesthetic solution resulted in a significant increase in heart rate over baseline readings. On day 1 postinjection, there was a 31% incidence of moderate/severe pain with the articaine solution and 20% incidence of moderate/severe pain with the lidocaine solution. The moderate/severe pain ratings decreased over the next 2 days. There were no significant differences between the articaine and lidocaine solutions. We concluded that the intraligamentary injection of 4% articaine with 1:100,000 epinephrine was similar to 2% lidocaine with 1:100,000 epinephrine for injection pain and postinjection pain in the mandibular first molar when administered with a computer-controlled local anesthetic delivery system. For both anesthetic solutions, heart rate did not significantly increase with the intraligamentary injection using the computer-controlled local anesthetic system.
PMCID: PMC2007494  PMID: 15675261
23.  The Analgesic Efficacy of Preoperative Oral Ibuprofen and Acetaminophen in Children Undergoing Adenotonsillectomy: A Randomized Clinical Trial 
Adenotonsillectomy is one of the most common surgical procedures in children. Several complications and morbidities are common after nasal surgeries and the most common is pain. Several techniques have been employed to reduce the severity of postoperative pain. One of the preoperative techniques is pre-emptive analgesia through preventive central hypersensitization. This technique is performed by applying analgesic methods before the onset of nociceptive stimuli, consequently decreasing postoperative analgesics requirements.
Preoperative oral drug administration for pain analgesia is performed in several methods. The aim of this study was to compare the analgesic effects of preoperatively administration of oral acetaminophen and ibuprofen.
Patients and Methods:
In a double-blinded, randomized placebo-controlled study, sixty 4-12 years old ASA I or II children scheduled for elective adenotonsillectomy, were assigned to receive either acetaminophen 15 mg/kg, ibuprofen 10 mg/kg or placebo 30 minutes before the operation. Postoperative pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS), upon arrival to the post anesthetic care unit (PACU) and ward. Findings were analyzed by SPSS version 17 using variance analysis and Tukey’s test.
The average pain intensities were significantly lower in acetaminophen group based on the CHEOPS in both PACU and ward compared to ibuprofen or placebo groups; but there was no difference in pain intensity between the ibuprofen and placebo groups. Pain intensity in PACU in Acetaminophen group was 7.05 ± 0.64 vs. 8.38 ± 1.20 in placebo group and 8.14 ± 0.85 in ibuprofen group, pain intensity in ward in the acetaminophen group was 6.0.87 ± 0.85in the acetaminophen group, vs. 8.04 ± 1.02 in placebo group, and 7.78 ± 0.78 in ibuprofen group.
This study showed that administration of oral acetaminophen 30 minutes preoperatively, resulted in significantly lower pain intensity in children undergoing adenotonsillectomy in PACU and ward, compared to ibuprofen and placebo.
PMCID: PMC3961035  PMID: 24660156
Acetaminophen; Ibuprofen; Pain, Postoperative
24.  The Effect of Local Injection of Epinephrine and Bupivacaine on Post-Tonsillectomy Pain and Bleeding 
Tonsillectomy is one of the most common surgeries in the world and the most common problem is post-tonsillectomy pain and bleeding. The relief of postoperative pain helps increase early food intake and prevent secondary dehydration. One method for relieving pain is peritonsillar injection of epinephrine along with an anesthetic, which has been shown to produce variable results in previous studies. Study Deign: Prospective case-control study. Setting: A tertiary referral centers with accredited otorhinolaryngology-head & neck surgery and anesthesiology department.
Materials and Methods:
Patients under 15 years old, who were tonsillectomy candidates, were assigned into one of three groups: placebo injection, drug injection before tonsillectomy, and drug injection after tonsillectomy. The amount of bleeding, intensity of pain, and time of first post-operative food intake were evaluated during the first 18 hours post operation.
The intensity of pain in the first 30 minutes after the operation was lower in the patients who received injections, but the difference was not significant during the first 18 hours. The intensity of pain on swallowing during the first 6 hours was also lower in the intervention groups as compared with the placebo group. The amount of bleeding during the first 30 minutes post operation was lower in the two groups who received injections, but after 30 minutes there was no difference.
Injection of epinephrine and bupivacaine pre- or post- tonsillectomy is effective in reducing pain and bleeding. The treatment also decreases swallowing pain in the hours immediately after surgery.
PMCID: PMC3846251  PMID: 24303442
Bleeding; Bupivacaine; Epinephrine; Post-tonsillectomy pain; Post-tonsillectomy; Tonsillectomy
25.  A Comparison of the Periodontal Ligament Injection Using 2% Lidocaine with 1:100,000 Epinephrine and Saline in Human Mandibular Premolars 
Anesthesia Progress  1987;34(5):181-186.
The purpose of this study is to evaluate, with the electric pulp tester, the anesthetic efficacy of the periodontal ligament injection using 2% lidocaine with 1:100,000 epinephrine and saline in human mandibular premolars. The periodontal ligament injection using 2% lidocaine with 1:100,000 epinephrine was found to be an effective technique for anesthetizing mandibular first premolars. However, the duration of profound pulpal anesthesia was approximately 10 minutes. The periodontal ligament injection using sterile saline was not an effective technique for anesthesia. Teeth mesial and distal to the injected tooth may also become anesthetized with this injection technique. The initial needle penetration and injection of the anesthetic solution in clinically healthy teeth were only mildly discomforting. No increase in tooth mobility was observed 45 minutes after the periodontal ligament injection. No clinically observable pulpal or periodontal damage was seen at 3 weeks after the injection.
PMCID: PMC2148545  PMID: 3479918

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