Tammisto, T.; Tigerstedt, I.
1 The intensity of postoperative pain is influenced by many factors, for example, individual variation, site of incision and type of operation, anaesthetic technique, and the interval from the end of operation to the appearance of pain. 2 These factors affect the efficacy of analgesics. 3 Mild analgesics provide adequate pain relief in half of our patients in the immediate postoperative phase when the pain is slight to moderate. 4 The maximum effect of mild analgesics corresponds to that produced by morphine 6-10 mg. Adequate analgesia may not therefore be provided for the treatment of severe postoperative pain unless narcotic analgesics have been used peroperatively. 5 When mild analgesics are combined with narcotics synergism is achieved. 6 As postoperative pain decreases with time, mild analgesics usually provide adequate pain relief on the first and following postoperative days. PMID:7437275
Sim, Chin-Keng; Xu, Pei-Chang; Pua, Hwee-Leng; Zhang, Guojing; Lee, Tat-Leang
Acupuncture has been shown to be effective in experimental and clinical acute pain settings. This study aims to evaluate the effect of preoperative electroacupuncture (EA) on intraoperative and postoperative analgesic (alfentanil and morphine) requirement in patients scheduled for gynaecologic lower abdominal surgery. Ninety patients were randomly assigned to one of three groups: Group I (control group)--received placebo EA for 45 minutes before induction of general anaesthesia (GA); Group II--preoperative EA instituted 45 minutes before induction of GA; Group III--45 minutes of postoperative EA. The Bispectral Index monitor was used intraoperatively to monitor the hypnotic effect of anaesthetic drugs, and alfentanil was titrated to maintain the blood pressure and pulse rate within +/- 15% of basal values. Postoperative pain was managed by intravenous morphine via a patient-controlled analgesia (PCA) device. Patients in Group II (0.44 +/- .15microg/kg/min) received less alfentanil than those in Group III (0.58 +/- .22 microg/kg/min) (p = p.024), but not significantly less than those in Group I 10.51 +/- 0.21 microg/kg/min) (p = 0.472). Postoperative morphine consumption was numerically lower in Group II compared with the other groups; however, the difference was statistically significant only during the period of 6-12 hours between Group II [0.03 (0.05) mg/kg] and Group I [0.10 (0.11) mg/kg] (p = 0.015), and Group II and Group III [0.08 (0.10) mg/kg] (p = 0.010). The 24-hour cumulative morphine consumption for Group II (0.52 +/- .19mg/kg) was less than that for either Group I I0.68 +/- 38mg/kg) or Group III (0.58 +/- .27mg/kg), but the difference did not reach significance. In conclusion, preoperative EA leads to a reduced intraoperative alfentanil consumption, though this effect may not be specific, and has a morphine sparing effect during the early postoperative period.
Lee, Mi Geum; Kim, Hyun Jung; Lee, Keun Hwa
Background Although opioids are the most commonly used medications to control postoperative pain in children, the analgesic effects could have a large inter-individual variability according to genotypes. The aim of this study was to investigate the association between single nucleotide polymorphisms and the analgesic effect of morphine for postoperative pain in children. Methods A prospective study was conducted in 88 healthy children undergoing tonsillectomy, who received morphine during the operation. The postoperative pain score, frequency of rescue analgesics, and side effects of morphine were assessed in the post-anesthesia care unit. The children were genotyped for OPRM1 A118G, ABCB1 C3435T, and COMT Val158Met. Results Children with at least one G allele for OPRM1 (AG/GG) had higher postoperative pain scores compared with those with the AA genotype at the time of discharge from the post-anesthesia care unit (P = 0.025). Other recovery profiles were not significantly different between the two groups. There was no significant relationship between genotypes and postoperative pain scores in analysis of ABCB1 and COMT polymorphisms. Conclusions Genetic polymorphism at OPRM1 A118G, but not at ABCB1 C3435T and COMT Val158Met, influences the analgesic effect of morphine for immediate acute postoperative pain in children. PMID:26839669
Beaver, W T; Feise, G A
In a double-study, using patients' subjective reports as indices of analgesia, the relative analgesic potency of intramuscular nalbuphine and morphine was determined in 56 postoperative patients. A total of 28 crossover comparisons (utilizing the twin passover, balanced four-point incomplete block design) were performed in two sequentially related experiments, each assay comparing 4 and 8 mg of morphine with either 3 and 6 or 6 and 12 mg of nalbuphine. When both intensity and duration of analgesia are considered (i.e., total analgesic effect), nalbuphine was 0.8 to 0.9 times as potent as morphine. In terms of peak analgesic effect, nalbuphine was 0.7 to 0.8 times as potent. Both the time-effect curves and the relative potency estimates suggest that nalbuphine has a slightly longer duration of action than morphine at doses that are equianalgesic in terms of peak effect. Side effects of the type usually noted after the administration of potent injectable analgesics to postoperative patients were observed after both morphine and nalbuphine. Although nalbuphine is a potent narcotic antagonist, no psychotomimetic reactions were observed.
Karci, A; Tasdogen, A; Erkin, Y; Aktaş, G; Elar, Z
Many clinical and experimental studies have suggested that diabetes or hyperglycemia alter opioid responsiveness. However, little information is available on the effects of diabetes mellitus on opioid requirements in the postoperative period. Sixty-four patients scheduled for elective, total abdominal hysterectomy were included into this prospective study to evaluate the effect of diabetes mellitus on morphine requirement in the postoperative period. A loading dose of morphine (50 micro g kg(-1)) was administered in the perioperative period. Postoperative analgesia consisted of intravenous morphine-PCA. No analgesic other than morphine was allowed during the study. In cases of inadequate analgesia intravenous 1 mg of morphine was given as a rescue analgesic. Cumulative morphine consumption, pain scores and morphine-related adverse effects were recorded. A total of 60 patients were evaluated: Group D, 30; and Group ND, 30. Patients in Group D received more morphine than those in Group ND (54.12 +/- 25.09 and 42.66 +/- 20.67, respectively). The difference in cumulative morphine consumption was higher in the first hour (P = 0.037) in diabetic patients and they required significantly more morphine in the last 24 h (P = 0.015). Postoperative pain scores were higher in the diabetic group. More patients in the diabetic group required rescue medication (26 vs. 19) and felt nauseous (25 vs. 14; P = 0.003). The findings of the study appear to support experimental and clinical impressions that the analgesic effect of morphine is attenuated in hyperglycemic conditions. Therefore, larger doses of morphine may be administered to diabetic patients for effective postoperative analgesia.
Lim, Dong Wook; Kim, Jae Goo; Kim, Yun Tai
Indian gooseberry (Emblica officinalis fruit), also known as “Amla” is one of the oldest edible fruits known in India. It has also traditionally been used to treat inflammation, and as an analgesic to treat wounds. However, experimental evidence for the analgesic effects of E. officinalis has been lacking. The present study investigated whether E. officinalis extracts exhibit analgesic effects in the plantar incision (PI) and spared nerve injury (SNI) pain-model rats. We evaluated the mechanical withdrawal threshold (MWT) using von Frey filaments, and pain-related behavior was determined after surgery based on ultrasonic vocalization (USV). The group treated with E. officinalis extracts at 300 mg/kg had significantly increased MWT values at 6 h and 24 h after the PI, and had a significantly reduced number of 22–27-kHz USVs at 6 h and 24 h after PI. Moreover, after 15 days of continuous treatment with E. officinalis extracts, the treated group showed significantly alleviated SNI-induced hypersensitivity and reduced pro-inflammatory cytokine levels. Thus, E. officinalis extracts have potential analgesic effects in both postoperative and neuropathic pain models in vivo. PMID:27898027
Lim, Dong Wook; Kim, Jae Goo; Kim, Yun Tai
Indian gooseberry (Emblica officinalis fruit), also known as "Amla" is one of the oldest edible fruits known in India. It has also traditionally been used to treat inflammation, and as an analgesic to treat wounds. However, experimental evidence for the analgesic effects of E. officinalis has been lacking. The present study investigated whether E. officinalis extracts exhibit analgesic effects in the plantar incision (PI) and spared nerve injury (SNI) pain-model rats. We evaluated the mechanical withdrawal threshold (MWT) using von Frey filaments, and pain-related behavior was determined after surgery based on ultrasonic vocalization (USV). The group treated with E. officinalis extracts at 300 mg/kg had significantly increased MWT values at 6 h and 24 h after the PI, and had a significantly reduced number of 22-27-kHz USVs at 6 h and 24 h after PI. Moreover, after 15 days of continuous treatment with E. officinalis extracts, the treated group showed significantly alleviated SNI-induced hypersensitivity and reduced pro-inflammatory cytokine levels. Thus, E. officinalis extracts have potential analgesic effects in both postoperative and neuropathic pain models in vivo.
Sen, Hüseyin; Yanarateş, Omer; Sızlan, Ali; Kılıç, Emre; Ozkan, Sezai; Dağlı, Güner
The aim of this study was first to find out the effect of music therapy on postoperative analgesia and second to determine the duration of its effect. Seventy patients who were undergoing elective cesarean delivery were enrolled. The patients were randomly allocated into two groups as follows: In Group 1, patients listened to music through a headphone for one hour after surgery, while in Group 2, patients did not listen to any music during the same period. In the postanesthesia care unit, patients were connected to a Patient Controlled Analgesia (PCA) device. The PCA device (tramadol 3 mg/ml) was set to deliver a bolus of 20 mg, with a lockout interval of 15 min and 4-hour maximal dose of 150 mg. Postoperative pain was assessed with a visual analog scale (VAS) and consumption of tramadol was recorded at 4, 8, 12, 16, 20 and 24 hours. There was a significant decrease in Group 1 with respect to PCA delivery frequency at the 4th hour postoperatively (p<0.05). Concerning the postoperative tramadol consumption, values measured at the 4th hour were significantly lower in Group 1 (p<0.05). The total amount of tramadol consumption and additional analgesic use in the postoperative 24 hours were again lower in Group 1 when compared with Group 2 (p<0.05). All VAS values were lower in Group 1 when compared with Group 2 (p<0.05). We suggest that music therapy given after surgery decreases postoperative pain in the first 24 hours and the analgesic consumption during the first four hours.
Hahn, T W; Mogensen, T; Lund, C; Jacobsen, L S; Hjortsoe, N-C; Rasmussen, S N; Rasmussen, M
Despite the widespread use of paracetamol for many years, the analgesic serum concentrations of paracetamol are unknown. Therefore the correlation between serum paracetamol concentrations and the analgesic effect was studied. Sixty-four women undergoing laparoscopic sterilization were included in a double-blind, placebo-controlled, randomized study. Patients were given i.v. propacetamol 40 mg kg(-1) (group H), 20 mg kg(-1) (group I), 10 mg kg(-1) (group L) or placebo after surgery. Alfentanil was available via patient-controlled analgesia (PCA) during the 4-h postoperative study period. The patients' self-reported pain was registered on the visual analog scale (VAS). A pharmacokinetic model was fitted to the paracetamol data. One to 3 h after injection of propacetamol the alfentanil consumption was significantly (P = 0.01-0.04) higher in the placebo group compared with groups H, I, and L receiving propacetamol. There were no significant differences between the amounts of alfentanil consumed in groups H, I, and L. Initial VAS-scores were moderate (5.4-6.2), and declined significantly (P < 0.0001) over time, with no difference between groups. Paracetamol followed an open two-compartment model with i.v. administration and first order elimination. The estimated concentrations immediately (t = 0) after injection were 56 mg l(-1) (H), 28 mg l(-1) (I) and 14 mg l(-1) (L). We showed a significant opioid-sparing effect of paracetamol in the immediate postoperative period. Pharmacokinetic data were in accordance with other studies. Our results suggest that a ceiling effect of paracetamol may be present at i.v. doses of 5 mg kg(-1), i.e. a serum concentration of 14 mg l(-1), which is a lower dose than previously suggested. Copyright Acta Anaesthesiologica Scandinavica 47 (2003)
Romans, Cory W; Gordon, Wanda J; Robinson, Duane A; Evans, Richard; Conzemius, Michael G
To evaluate the analgesic effects of topical administration of bupivacaine, i.m. administration of butorphanol, and transdermal administration of fentanyl in cats undergoing onychectomy. Prospective study. 27 healthy adult cats. Cats were randomly assigned to 1 of 3 treatment groups, and unilateral (left forefoot) onychectomy was performed. Gait analysis was performed before and 1, 2, 3, and 12 days after surgery. All forces were expressed as a percentage of the cat's body weight. On day 2, peak vertical force (PVF) was significantly decreased in cats treated with bupivacaine, compared with cats treated with butorphanol or fentanyl. The ratio of left forelimb PVF to PVF of the other 3 limbs was significantly lower on day 2 in cats treated with bupivacaine than in cats treated with fentanyl. No significant differences in vertical impulse (VI) were found between groups on any day. Values for PVF, VI, and the PVF ratio increased progressively following surgery. However, for all 3 groups, values were still significantly decreased, compared with baseline values, 12 days after surgery. Results suggest that limb function following onychectomy is significantly better in cats treated with fentanyl transdermally or butorphanol i.m. than in cats treated with bupivacaine topically. Regardless of the analgesic regimen, limb function was still significantly reduced 12 days after surgery, suggesting that long-term analgesic treatment should be considered for cats undergoing onychectomy. Irrigation of the surgical incisions with bupivacaine prior to wound closure cannot be recommended as the sole method for providing postoperative analgesia in cats undergoing onychectomy.
Pereira, Francisco Elano Carvalho; Mello, Irene Lopes; Pimenta, Fernando Heladio de Oliveira Medeiros; Costa, Debora Maia; Wong, Deysi Viviana Tenazoa; Fernandes, Claudia Regina; Lima Junior, Roberto César; Gomes, Josenília M. Alves
This study aims to evaluate the viability of a clinical model of remote ischemic preconditioning (RIPC) and its analgesic effects. It is a prospective study with twenty (20) patients randomly divided into two groups: control group and RIPC group. The opioid analgesics consumption in the postoperative period, the presence of secondary mechanical hyperalgesia, the scores of postoperative pain by visual analog scale, and the plasma levels interleukins (IL-6) were evaluated. The tourniquet applying after spinal anesthetic block was safe, producing no pain for all patients in the tourniquet group. The total dose of morphine consumption in 24 hours was significantly lower in RIPC group than in the control group (p = 0.0156). The intensity analysis of rest pain, pain during coughing and pain in deep breathing, showed that visual analogue scale (VAS) scores were significantly lower in RIPC group compared to the control group: p = 0.0087, 0.0119, and 0.0015, respectively. There were no differences between groups in the analysis of presence or absence of mechanical hyperalgesia (p = 0.0704) and in the serum levels of IL-6 dosage over time (p < 0.0001). This clinical model of remote ischemic preconditioning promoted satisfactory analgesia in patients undergoing conventional cholecystectomy, without changing serum levels of IL-6. PMID:27446611
Wang, B; Tang, J; White, P F; Naruse, R; Sloninsky, A; Kariger, R; Gold, J; Wender, R H
Given the inherent side effects associated with both opioid and nonopioid analgesic drugs, a nonpharmacologic therapy that could decrease the need for analgesic medication would be valuable. We designed a sham-controlled study to assess the effect of the intensity of transcutaneous acupoint electrical stimulation (TAES) on postoperative patient-controlled analgesia (PCA) requirement for hydromorphone (HM), the incidence of opioid-related side effects, and the recovery profile after lower abdominal surgery. One hundred one healthy consenting women undergoing lower abdominal procedures with a standardized general anesthetic technique were randomly assigned to one of four postoperative analgesic treatment regimens: Group I (n = 26) PCA only; Group II (n = 25), PCA + sham-TAES (no electrical stimulation); Group III (n = 25), PCA + low-TAES (4-5 mA of electrical stimulation); Group IV (n = 25), PCA + high-TAES (9-12 mA of electrical stimulation). The PCA device was programmed to deliver HM, 0.2-0.4 mg intravenously boluses "on demand," with a minimum lockout interval of 10 min. The TAES skin electrodes were placed at the Hegu acupoint on the nondominant hand and on both sides of the surgical incision. The TAES frequency was set in the dense-and-disperse mode, alternating at 2 Hz and 100 Hz every 3 s, with stimulation of the hand and incision alternated every 6 s. The patients in Groups II-IV were instructed to use TAES every 2 h for 30 min while awake. After discontinuation of PCA, oral pain medications were administered on demand. The postoperative PCA-HM requirement, pain scores, opioid-related side effects, and requirements for antiemetic and antipruritic medication were recorded. High-TAES decreased the HM requirement by 65% and reduced the duration of PCA therapy, as well as the incidence of nausea, dizziness, and pruritus. Low-TAES produced a 34% decrease in the HM requirement compared with only 23% in the "sham" TAES group. We conclude that high-TAES produced a
Nesek-Adam, Visnja; Rasić, Zarko; Schwarz, Dragan; Grizelj-Stojcić, Elvira; Rasić, Domagoj; Krstonijević, Zoran; Markić, Ana; Kovacević, Marko
The optimal anesthetic technique for peripheral vascular surgery remains controversial. The purpose of this study was to evaluate the effect of spinal versus general anesthesia on postoperative pain, analgesic requirements and postoperative comfort in patients undergoing peripheral vascular surgery. A total of 40 patients scheduled for peripheral vascular surgery were randomly assigned to two groups of 20 patients each to receive general anesthesia (GA) or spinal anesthesia (SA). In GA group, anesthesia was induced using thiopental and fentanyl. Vecuronium was used for muscle relaxation. Anaesthesia was maintained with isoflurane and nitrous oxide. In the SA group, hyperbaric 0.5% bupivacaine was injected into the subarachnoid space. Postoperative pain was assessed for 24 hours by a visual analog scale during three assessment periods: 0-4, 4-12 and 12-24 h as well as analgesic requirements. Patients were also asked to assess their postoperative state as satisfactory or unsatisfactory with regard to the pain, side effects and postoperative nausea and vomiting. Visual analogue scale (VAS) pain score was significantly lower in the group SA compared with group GA. This effect was mainly due to the lower pain score during the first study period. The patients received general anesthesia also reported a significantly higher rate of unsatisfactory postoperative comfort than those receiving spinal anesthesia. We conclude that spinal anesthesia is superior to general anesthesia when considering patients' satisfaction, side effects and early postoperative analgesic management.
Morgaz, J; Navarrete, R; Muñoz-Rascón, P; Domínguez, J M; Fernández-Sarmiento, J A; Gómez-Villamandos, R J; Granados, M M
The objective of this study was to compare the postoperative analgesic effects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02 mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48 h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy. Copyright © 2013 Elsevier Ltd. All rights reserved.
Semënov, F V; Kade, A Kh; Banashek-Meshchiarkova, T V; Vartanian, M S
The objective of the present work was to study peculiarities of the analgesic action of therapeutic electrical stimulation (TES therapy) in the early postoperative period in the patients who underwent tonsillectomy. A total of 60 patients admitted for this surgery to the specialized otorhinolaryngological department were available for observation. They were divided into two groups depending on the pain relief strategy. The patients of the study group (n=30) underwent courses of transcranial electrical stimulation on a daily basis (from the onset of hospitalization) in addition to the administration of a standard analgetic. The standard dose of tramadol (2.0 ml) was given to the patients of the control group (n=30) who complained of strong pain. The results of the objective and subjective estimations indicate that the degree of pharyngeal pain in the patients treated with TES therapy and the standard analgetic was significantly different. The patients receiving TES therapy could sooner resume their habitual diet and required smaller amounts of the analgetic which makes this modality a cost-effective supplement to the standard postoperative treatment.
Sitilci, Abdullah Tolga; Ozyuvacı, Emine; Alkan, Zeynep; Demirgan, Serdar; Yiğit, Ozgür
We aimed to investigate the effect of dexmedetomidine infusion on the amount of opioid that is consumed during the operation, the amount of analgesic that the patient requires after the operation and on pain scores. Forty patients who were ASA I-II, between 18-50 years old, and who were scheduled for mastoidectomy operation were included in the study. Patients were randomized into two groups as group Dexmedetomidine (Group D) and group Placebo (Group P). Dexmedetomidine was administered at the rate of 0.5 mcg/kg/hour to the cases in Group D during operation and 9% NaCl was administered at the same rate and volume to the cases in Group P. Patients were connected to a Patient-Controlled Analgesia (PCA) device prepared with tramadol. Patients were followed for 24 hours. Ramsay Sedation Scale, visual analog scale (VAS), non-invasive systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), end-tidal sevoflurane, extubation times, total remifentanil consumption, total demand of PCA, and total tramadol consumption from PCA were recorded. No difference was determined between groups in demographic level and extubation times. Total remifentanil consumption, additional analgesic requirement, total demand of PCA, total amount of PCA consumption, and mean VAS were higher in the control group. First demand time of PCA was longer in the study group. Results of our study demonstrated that continuous infusion of dexmedetomidine during the operation could provide postoperative patient comfort without affecting the extubation time while concomitantly decreasing the consumption of tramadol.
Camargo, Janaina B; Steagall, Paulo V M; Minto, Bruno W; Lorena, Sílvia Elaine Rodolfo de Sá; Mori, Eduardo S; Luna, Stelio P L
To compare the post-operative analgesic effects of butorphanol or firocoxib in dogs undergoing ovariohysterectomy. Prospective, randomized, blinded, clinical trial. Twenty-five dogs >1 year of age. Dogs received acepromazine intramuscularly (IM), 0.05 mg kg(-1) and either butorphanol IM, 0.2 mg kg(-1) (BG, n = 12) or firocoxib orally (PO), 5 mg kg(-1) (FG, n = 13), approximately 30 minutes before induction of anesthesia with propofol. Anesthesia was maintained with isoflurane. Ovariohysterectomy was performed by the same surgeon. Pain scores using the dynamic and interactive visual analog scale (DIVAS) were performed before and at 1, 2, 3, 4, 6, 8 and 20 hours after the end of surgery by one observer, blinded to the treatment. Rescue analgesia was provided with morphine (0.5 mg kg(-1)) IM and firocoxib, 5 mg kg(-1) (BG only) PO if DIVAS >50. Groups were compared using paired t-tests and Fisher's exact test (p < 0.05). Data are presented as mean ± SD. The BG required significantly less propofol (BG: 2.6 ± 0.59 mg kg(-1); FG: 5.39 ± 0.7 mg kg(-1)) (p < 0.05) but the anesthesia time was longer (BG: 14 ± 6, FG: 10 ± 4 minutes). There were no differences for body weight (BG: 7.9 ± 5.0, FG: 11.5 ± 4.6 kg), sedation scores, and surgery and extubation times (BG: 10 ± 2, 8 ± 5 minutes; FG: 9 ± 3, 8 ± 4 minutes, respectively) (p > 0.05). The FG had significantly lower pain scores than the BG at 1, 2 and 3 hours following surgery (p < 0.05). Rescue analgesia was administered to 11/12 (92%) and 2/13 (15%) dogs in the BG and FG, respectively (p < 0.05). Firocoxib produced better post-operative analgesia than butorphanol. Firocoxib may be used as part of a multimodal analgesia protocol but may not be effective as a sole analgesic. © 2011 The Authors. Veterinary Anaesthesia and Analgesia © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.
Giordano, Tatiana; Steagall, Paulo V M; Ferreira, Tatiana H; Minto, Bruno W; de Sá Lorena, Sílvia Elaine Rodolfo; Brondani, Juliana; Luna, Stelio P L
To compare the postoperative analgesic effects of intravenous (IV), intramuscular (IM), subcutaneous (SC) or oral transmucosal (OTM) buprenorphine administered to cats undergoing ovariohysterectomy. Randomized, prospective and blinded clinical trial. 100 female cats. Cats were assigned to receive 0.01 mg kg(-1) of buprenorphine administered by the IV, IM, SC or OTM route (n = 25/group). Buprenorphine was made up to 0.3 mL with 0.9% saline. DIVAS (0-100 mm) and simple descriptive scale (SDS) (from 0 to 4) pain and sedation scores were assigned to each cat before and 1, 2, 3, 4, 6, 8, 12 and 24 hours after ovariohysterectomy. Buprenorphine and carprofen were administered for rescue analgesia. Data were analyzed using anova and Fisher's exact test (p < 0.05). There were no significant differences between groups for breed, body weight, anesthetic time or surgery time (p > 0.05). There were no significant differences between groups for sedation scores at any time. SDS pain scores did not detect any differences between groups (p > 0.05). DIVAS pain scores after OTM administration were significantly higher than IV and IM administration at 1 hour and at 3, 4, 6, 8 and 12 hours, respectively (p < 0.05). DIVAS pain scores after SC administration were significantly higher than IV and IM administration at 2 hours and at 2, 3, 4, 8, 12 and 24 hours (p < 0.05), respectively. Six, four, 13 and 17 cats that received IV, IM, SC and OTM buprenorphine required rescue analgesia, respectively. There was a significantly higher incidence of treatment failure in cats that received SC and OTM buprenorphine compared with cats that received IV and IM buprenorphine (p < 0.05). IV and IM administration of buprenorphine provided better postoperative analgesia than SC or OTM administration of the drug and these routes of administration should be preferred when buprenorphine is administered to cats.
Yi, Yusheng; Zhao, Mingqiang; Xu, Fenghe; Liu, Chuansheng; Yin, Yanwei; Yu, Junmin
Our study aimed at evaluating the association between α-calcitonin gene-related peptide (CGRP) 4218T/C polymorphism and the patient-controlled analgesic (PCA) effect of fentanyl on Chinese Han population. 98 patients were involved in the experiment, but only 92 patients completed the experiment. 0.1 mg/kg fentanyl was given to the patients through intravenous injection ten minutes before the ending of surgery. The patients achieved PCA by controlling the fentanyl infusion pump and a single dose was 1 mg. The CGRP 4218T/C polymorphism was genotyped with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The fentanyl consumption within the 72 hours after the surgery was recorded and the pain was assessed with numeric rating scale (NRS) method. The patients were divided into three groups of wild homozygote (T/T), heterozygote (T/C), and mutant homozygote (C/C). At the 6th hour and the 12th hour after the surgery, the fentanyl consumption for PCA of the T/C group was significantly higher than the T/T group (P<0.05). Meanwhile, the fentanyl consumption of the C/C group was much higher than the T/T group (P<0.05) at the 12th hour and the 24th hour. Besides, the fentanyl consumption of the C/C group was more than the T/C group (P<0.05) at the 24th hour. The differences in NRS scores, Ramsey scores, and postoperative adverse reactions between each group at all time points were not statistically significant. CGRP 4218T/C polymorphism may be associated with the postoperative fentanyl consumption for analgesia.
Yi, Yusheng; Zhao, Mingqiang; Xu, Fenghe; Liu, Chuansheng; Yin, Yanwei; Yu, Junmin
Purpose: Our study aimed at evaluating the association between α-calcitonin gene-related peptide (CGRP) 4218T/C polymorphism and the patient-controlled analgesic (PCA) effect of fentanyl on Chinese Han population. Methods: 98 patients were involved in the experiment, but only 92 patients completed the experiment. 0.1 mg/kg fentanyl was given to the patients through intravenous injection ten minutes before the ending of surgery. The patients achieved PCA by controlling the fentanyl infusion pump and a single dose was 1 mg. The CGRP 4218T/C polymorphism was genotyped with polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. The fentanyl consumption within the 72 hours after the surgery was recorded and the pain was assessed with numeric rating scale (NRS) method. Results: The patients were divided into three groups of wild homozygote (T/T), heterozygote (T/C), and mutant homozygote (C/C). At the 6th hour and the 12th hour after the surgery, the fentanyl consumption for PCA of the T/C group was significantly higher than the T/T group (P<0.05). Meanwhile, the fentanyl consumption of the C/C group was much higher than the T/T group (P<0.05) at the 12th hour and the 24th hour. Besides, the fentanyl consumption of the C/C group was more than the T/C group (P<0.05) at the 24th hour. The differences in NRS scores, Ramsey scores, and postoperative adverse reactions between each group at all time points were not statistically significant. Conclusions: CGRP 4218T/C polymorphism may be associated with the postoperative fentanyl consumption for analgesia. PMID:26191294
Kara, Bilge; Baskurt, Ferdi; Acar, Serap; Karadibak, Didem; Ciftci, Lugen; Erbayraktar, Serhat; Gokmen, Ali Necati
The aim of our study was to examine the effects of the use of Transcutaneous Electrical Nerve Stimulation (TENS) in patients who had undergone spinal surgery on pain, functionality, depression and consumption of analgesic agents. Fifty-Four patients were randomized and placed into two groups, patient-controlled analgesia (PCA) plus TENS and only PCA. To assess the pain levels of the patients, the Visual Analog Scale (VAS) was used. In the assessment of their functional levels, the Timed Up and Go test (TUG) was utilized and in the assessment of their depression, the Beck Depression Inventory (BDI) was used. The measurements were performed before the operation and on the first and second postoperative days. The side effects were recorded from the analgesic agents. During the first and second days after the operation, a decrease in the pain levels was noticed in the TENS group (p < 0.05. In the TENS group, the consumption of analgesic agents also decreased and thus side effects were less frequent. From the viewpoint of functional and depression levels, no significant difference between the groups was noticed (p > 0.05). TENS was effective in reducing analgesic agent-related side effects and in reducing analgesic consumption. In addition, TENS also decreased activity related pain.
Rantala, Maija; Hartikainen, Sirpa; Kvist, Tarja; Kankkunen, Päivi
Registered nurses (RNs) play a pivotal role in treating pain and preventing and recognizing the adverse effects (AEs) of analgesics in patients with dementia. The purpose of this study was to determine RNs' knowledge of potentially clinically relevant AEs of analgesics. A descriptive, cross-sectional study design was used. In all, 267 RNs treating orthopedic patients, including patients with dementia, in 7 university hospitals and 10 central hospitals in Finland, completed a questionnaire. Analgesics were defined according to the Anatomic Therapeutic Classification as strong opioids, weak opioids, nonsteroidal anti-inflammatory analgesics (NSAIDs), and paracetamol. Definitions of AEs were based on the literature. Logistic regression analysis was applied to analyze which variables predicted nurses' knowledge. The RNs had a clear understanding of the AEs of paracetamol and strong opioids. However, the AEs of NSAIDs, especially renal and cardiovascular AEs, were less well known. The median percentage of correct answers was 87% when asked about strong opioids, 73% for weak opioids, and 60% for NSAIDs. Younger RNs had better knowledge of opioid-related AEs (odds ratio [OR] per 1-year increase, 0.97; 95% confidence interval [CI], 0.94-1.00) and weak opioids (OR, 0.96; 95% CI, 0.93-0.99). This study provides evidence of a deficiency in RNs' knowledge, especially regarding the adverse renal and cardiovascular effects of NSAIDs. Such lack of knowledge indicates that hospitals may need to update the knowledge of older RNs, especially those who treat vulnerable patients with dementia.
Dubois, Philippe E; Ossemann, Michel; de Fays, Katalin; De Bue, Pascale; Gourdin, Maximilien; Jamart, Jacques; Vandermeeren, Yves
Ultimately, the experience of pain derives from changes in brain excitability. Therefore, modulating the excitability of cortical areas involved in pain processing may become an attractive option in the context of multimodal analgesia during the postoperative period. Repetitive transcranial magnetic stimulation (rTMS) can reduce morphine consumption during the postoperative period after gastric bypass surgery. We tested the potential of another method of noninvasive brain stimulation, transcranial direct current stimulation (tDCS), to reduce morphine consumption or pain perception during the postoperative period. Fifty-nine ASA I to II patients undergoing lumbar spine surgery were randomized to receive anodal (n=20), cathodal (n=20), or sham (n=19) tDCS in the recovery room in a double-blind manner. Morphine consumption administrated through patient-controlled analgesia (PCA) was the primary outcome; pain perception as measured by visual analog scale was the secondary outcome. There were no statistically significant differences between the 3 groups of patients, either for PCA morphine consumption or for pain scores. Several factors may explain the observed lack of impact of tDCS on PCA morphine consumption and pain perception: the method of brain stimulation (tDCS/rTMS), potential interactions with anesthetic drugs, differences in patients population (gastric bypass surgery/lumbar spine surgery), and the previous experience of pain and chronic consumption of analgesic drugs. Further studies with tDCS should be performed before concluding that tDCS is inefficient for postoperative pain control, because noninvasive brain stimulation methods, such as rTMS and tDCS, may become attractive in the setting of multimodal analgesia.
Kol, Emine; Alpar, Sule Ecevit; Erdoğan, Abdullah
The purpose of this study was to investigate the efficiency of preoperative pain management education and the role of analgesics administration before the onset of pain postoperatively. The study was a prospective, randomized, and single-blind clinical trial, which was conducted January 1, 2008 through October 1, 2008 in the Thoracic Surgery Unit of Akdeniz University Hospital. A total of 70 patients who underwent thoracotomy (35 in the control group and 35 in the study group) were included in the study. Of the patients, 70% (n = 49) were male and 30% (n = 21) were female. Mean age was 51 ± 10 years (range = 25-65). The same analgesia method was used for all patients; the same surgical team performed each operation. Methods, including preemptive analgesia and placement of pleural or thoracic catheter for using analgesics, that were likely to affect pain level, were not used. The same analgesia medication was used for both patient groups. But the study group, additionally, was educated on how to deal with pain preoperatively and on the pharmacological methods to be used after surgery. An intramuscular diclofenac Na 75 mg was administered to the study group regardless of whether or not they reported pain in the first two postoperative hours. The control group did not receive preoperative education, and analgesics were not administered to them unless they reported pain in the postoperative period. The routine analgesics protocol was as follows: diclofenac Na 75 mg (once a day) intramuscular administered upon the complaint of pain following extubation in the postoperative period and 20 mg mepederin intravenously (maximum dose, 100 mg/day), in addition, when the patient expressed pain. Pain severity was assessed during the second, fourth, eighth, 16th, 24th, and 48th hours, and marked using the Verbal Category Scale and the Behavioral Pain Assessment Scale. Additionally, the total dose of daily analgesics was calculated. The demographic characteristics showed a
Castel, David; Naveh, Michael; Aharon, Arnon; Doron, Ofer; Meilin, Sigal
Local anesthetic infusion techniques have been reported to reduce opiate requirements and pain scores following different kinds of surgery, including orthopedic surgery, inguinal hernia, and Cesarean surgery in women. PRF-108 and PRF-110 formulations were applied to the wound space in an incisional model in pigs to test the hypothesis that these formulations have better and longer analgesic effects than the commercially available ropivacaine solution (Naropin(®), AstraZeneca). The data show significantly better analgesic activity with PRF-108 and PRF-110 compared to ropivacaine. The duration of the analgesic efficacy of PRF-108 and PRF-110 was at least five times longer than that was measured following treatment with ropivacaine. The data further suggest that active clearance from the injection site (the wound) is much slower for PRF-108 and PRF-110 than for the commercial ropivacaine solution. Assessing the local concentration of PRF compounds and commercially available ropivacaine solution suggests that active clearance from the injection site (the wound) is much slower for PRF-108 and PRF-110 than for ropivacaine. PainReform.
Oza, Vrinda P; Parmar, Vandana; Badheka, Jigisha; Nanavati, Dharam S; Taur, Pradip; Rajyaguru, Ajay M
AIMS: This prospective double-blinded study was designed with the aim of comparing the analgesic effect of intraperitoneal instillation of dexmedetomidine with bupivacaine with that with bupivacaine alone in patients undergoing laparoscopic surgeries. MATERIALS AND METHODS: A total of 100 patients of either sex undergoing elective laparoscopic surgery were randomly divided into two groups containing 50 patients in each group. Group B received intraperitoneal instillation with 50 mL of bupivacaine 0.25% (125 mg) and groups B + D received 50 mL of bupivacaine 0.25% (125 mg) + 1 μg/kg of dexmedetomidine. Pain was assessed using visual analogue scale (VAS) at 0.5 h, 1 h, 2 h, 4 h, 6 h, and 24 h after the surgery. The requirement of rescue analgesics were recorded. RESULT: Duration of analgesia was longer in group B+D (14.5 hr) compared to group B (13.06 hr). The requirement of rescue analgesic in 24 hours was less in group B+D (1.76) compared to group B (2.56) which were statistically significant (P < 0.05). The mean number of total rescue analgesia given in 24 h was less in group B+D was 1.76 whereas in group B was 2.56 that were statistically significant. CONCLUSION: Intraperitoneal instillation of dexmedetomidine with bupivacaine prolongs the duration of postoperative analgesia as compared to that with bupivacaine alone. And also there is less number of rescue analgesics that are required postoperatively when dexmedetomidine is supplemented as an adjuvant to bupivacaine. PMID:27279399
Yaghoubi, Siamak; Pourfallah, Reza; Barikani, Ameneh; Kayalha, Hamid
postoperative pain increases the activity of the sympathetic system, causes hypermetabolic conditions, retains salt and water, increases glucose, fatty acid lactate and oxygen consumption, weakens the immunity system which delays wound healing. Our object was comparison of the analgesic effect of morphine and paracetamol in the patients undergoing laparotomy, using PCA method. Seventy patients who had undergone laparotomy were studied using double blind randomized clinical trial (35 patients received morphine and 35 paracetamol) in the Shahid Rajaee Center and Velayat Hospital (Qazvin, Iran). People using opioids, painkillers and sedatives regularly and in large doses and patients with a history of lung or liver problems did not participate in this project. The parameters of the severity of pain and nausea (VAS), hemodynamic changes (BP and HR), pruritus, arterial oxygen desaturation and patient satisfaction (VAS) of both groups were measured by a third party (trained colleague). The data was analyzed using SPSS 16 statistical software then descriptive results were extracted and ultimately the groups were compared using the following statistical tests: student's T-test, chi 2 and Fisher's exact test (P<0.05). The mean age of the participants was 45±12.5 years. Women constituted 24.3% of the patients and men 75.7%. The average pain severity for morphine and paracetamol groups (VAS) was 5.3±2.2and 6.37±1.7 after2 hours and reached 1.91±1.3 and 2.49±1.3 after 8 hours (after the operation) respectively. There was a significant difference between the groups after 2 and 4 hours in terms of pain severity (after 2 hours P=0.007 and after 4 hours P=0.047). However there was no significant difference between the average pain severity of the studied groups (after 6 hours P=0.4 and 8 hours P=0.08). After 8 hours, the average nausea severity was the minimum in both groups being 1.71±1.6 and 1.43±1.1 in morphine and paracetamol groups respectively. Nausea severity was
Rosales, Alvina; Fortier, Michelle A.; Campos, Belinda; Kain, Zeev N.
Background/Objectives The present study examined whether parental perceptions of children’s pain impacted home-based pain management following outpatient surgery in a sample of Latino families from low socioeconomic backgrounds. Methods Latino parents of children (n = 161) who underwent outpatient surgery were recruited for this study and completed measures assessing attitudes on pain and analgesic use (Parental Pain Expression Perceptions and Medication Attitudes Questionnaire) before their child’s surgery. Parents also rated their child’s pain after their child’s surgery using the Parent Postoperative Pain Measure and collected data on the amount of analgesics they gave to their child on the first postoperative day. Hierarchical regression analyses examined whether parental attitudes predicted pain assessment and management at home. Results A majority of parents reported multiple misconceptions regarding children’s pain and fears of side effects as well as avoidance of analgesic use. For example, over 80% reported believing that a child always tells their parents when they are in pain. Hierarchical regression analyses found that more fear and avoidance regarding analgesic use for children’s pain predicted parents’ providing fewer doses of analgesic to their children on the first postoperative day (β = −0.21, p = 0.028). Conclusions Preoperative parents’ beliefs regarding analgesics for treatment of children’s pain may adversely impact parent postoperative analgesic administration at home in Latino families. PMID:26792407
Tse, Mimi M Y; Chan, M F; Benzie, Iris F F
The prevalence of unrelieved postoperative pain is high and may lead to adverse effects including prolonged hospitalization and delayed recovery. Distraction may be an effective pain-relieving strategy, and can be implemented by several means including affective imaging, games, and possibly music. The aim of this study was to explore the effect of music therapy on postoperative pain. Fifty-seven patients (24 females, 33 males; mean +/- SD age 39.9 +/- 14.35 years [range 15 to 69 years] were matched for age and sex and then nonselectively assigned to either an experimental (n = 27) or a control (n = 30) group. Music was played intermittently to members of the experimental group during the first 24 hour postoperative period. Pain intensity was measured using the Pain Verbal Rating Scales (VRS). Significant decreases in pain intensity over time were found in the experimental group compared to the control group (p < 0.0001). In addition, the experimental group had a lower systolic blood pressure and heart rate, and took fewer oral analgesics for pain. These findings suggest that music therapy is an effective nonpharmacologic approach for postoperative pain management.
Simavli, S; Kaygusuz, I; Kinay, T; Akinci Baylan, A; Kafali, H
Pain is a common distressing adverse effect in the early postoperative period following caesarean section. The aim of this study was to investigate the effect on postoperative pain, analgesic requirement and haemodynamic profile of placing a suprafacial bupivacaine-soaked absorbable gelatin sponge in the caesarean section wound. A total of 164 healthy patients scheduled to undergo general anaesthesia for elective caesarean section were randomised to a study group (n=81) or a control group (n=83). In the study group, a bupivacaine-soaked absorbable gelatin sponge was placed subcutaneously in the caesarean section wound. Intramuscular diclofenac 75 mg was given to all patients at 8-h intervals during the first 24h. Postoperatively, visual analogue scale pain scores, requirement for pethidine and diclofenac and changes in blood pressure and heart rate were compared between groups. Pain scores were lower in the study group compared to the control group at all assessments (P<0.001). During the first eight hours after surgery, fewer patients in the study group required rescue pethidine compared with the control group (4 vs. 33, P<0.001). In the study group, total opioid and diclofenac consumption was lower (P<0.001), and blood pressure and heart rate were lower (P<0.001) compared to the control group. Suprafascial wound placement of a bupivacaine-soaked absorbable gelatin sponge improved postoperative analgesia and decreased opioid consumption following caesarean section. Copyright © 2014 Elsevier Ltd. All rights reserved.
Sethi, Priyank; Agarwal, Manish; Chourasia, Hemant Ramesh; Singh, Mahesh Pratap
Introduction: One of the aims of root canal treatment is to prevent or eliminate pain. Postoperative endodontic pain control continues to be a significant challenge. Aim: To compare and evaluate the effect of single oral dose of 100 mg of tapentadol, 400 mg of etodolac, or 10 mg of ketorolac as a pretreatment analgesic for the prevention and control of postoperative endodontic pain in patients with symptomatic irreversible pulpitis. The incidence of side effects was recorded as secondary outcome. Materials and Methods: Sixty emergency patients with moderate to severe pain, diagnosed with symptomatic irreversible pulpitis were randomly allocated (1:1:1) to any of the three groups; tapentadol, etodolac, or ketorolac. Medications were administered 30 min before beginning of the endodontic treatment. Patients recorded pain intensity on 10 cm visual analog scale (VAS) after treatment, for upto 24 h. Results: At 24 h, mean ±standard deviation (SD) of VAS scores (in cm) for tapentadol, etodolac, and ketorolac were 0.89 ± 0.83, 2.68 ± 2.29, and 0.42 ± 0.69, respectively. Kruskal-Wallis (K-W) test showed significant difference among the three groups (P = 0.001). Mann-Whitney test showed significantly lower VAS scores in tapentadol and ketorolac than etodolac group (P = 0.013 and 0.001, respectively). Conclusions: Single oral dose of 10 mg of ketorolac and 100mg of tapentadol as a pretreatment analgesic significantly reduced postoperative endodontic pain in patients with symptomatic irreversible pulpitis when compared to 400 mg of etodolac. PMID:25506136
Köroğlu, Süleyman; Takmaz, Suna Akin; Kaymak, Cetin; Narli, Altuğ; Karalezli, Kubilay; Dikmen, Bayazit
We studied the effect of preoperative 3-in-1 block for total hip replacement surgery on postoperative pain and tramadol consumption during patient-controlled analgesia. Thirty ASA I-II patients undergoing elective total hip arthroplasty (THA) were included in the study. Patients were randomly divided into 2 groups; Group I: Patients who received 3-in-1 block with 40 ml of 0.25% bupivacaine 30-minutes before surgery and later received general anesthesia, Group II: Patients who received only a simple needle puncture at the operation site 30-minutes before surgery and later received general anesthesia. All patients received intravenous tramadol at the end of surgery via a PCA device. Pain was evaluated at 0,1/2,1,4,8,12,24 and 48 h at rest and on movement of the hip, using a 10 cm VAS. The average intraoperative fentanyl consumption was lower in Group I than in Group II. VAS scores were significantly lower in group I, both at rest and during movement at all timepoints over in the first postoperative 12 h and also during movement 24 h postoperatively. However differences in VAS scores weren't clinically significant after 4 hours. In the recovery room, Group I VAS scores were only a third of Group II, both at rest and movement (p=0.0001). Total tramadol consumption was lower in Group I (633.0+/-119.3 mg) than in Group II (991.1+/-41.0 mg). Patient satisfaction scores were higher in Group I than in Group II. We concluded that preoperative 3-in-1 block with 40 ml-0,25% bupivacaine provides effective postoperative pain relief for elective THA, reducing intra-and postoperative analgesic consumption without increase in side effects.
Mehrvarzfar, P; Abbott, P V; Saghiri, M A; Delvarani, A; Asgar, K; Lotfi, M; Karamifar, K; Kharazifard, M J; Khabazi, H
To compare the effects of single doses of three oral medications on postoperative pain following instrumentation of root canals in teeth with irreversible pulpitis. In this double-blind clinical trial, 100 patients who had anterior or premolar teeth with irreversible pulpitis without any signs and symptoms of acute or chronic apical periodontitis and moderate to severe pain were divided by balanced block random allocation into four groups of 25 each, a control group receiving a placebo medication, and three experimental groups receiving a single dose of either Tramadol (100 mg), Novafen (325 mg of paracetamol, 200 mg ibuprofen and 40 mg caffeine anhydrous) or Naproxen (500 mg) immediately after the first appointment where the pulp was removed, and the canals were fully prepared. The intensity of pain was scored based on 10-point VAS before and after treatment for up to 24 h postoperatively. Data were submitted to repeated analysis of variance. At the 6, 12 and 24 h postoperative intervals after drug administration, the intensity of pain was significantly lower in the experimental groups than in the placebo group (P < 0.01). Tramadol was significantly less effective (P < 0.05) than Naproxen, and Novafen that were similar to each other (P > 0.05). A single oral dose of Naproxen, Novafen and Tramadol taken immediately after treatment reduced postoperative pain following pulpectomy and root canal preparation of teeth with irreversible pulpitis. © 2011 International Endodontic Journal.
Fabre, Hebert S. C.; Navarro, Ricardo L.; Oltramari-Navarro, Paula V.P.; Oliveira, Rodrigo F.; Pires-Oliveira, Deise A. A.; Andraus, Rodrigo A. C.; Fuirini, Nelson; Fernandes, Karen B. P.
[Purpose] This study aimed to evaluate the anti-inflammatory and analgesic effects of intraoral application of low-level laser therapy (660 nm) to control pain, swelling and interincisal opening following the extraction of mandibular third molars. [Subjects and Methods] Ten patients underwent removal of lower third molars using the same surgical protocol and pharmacological approach. In the postoperative period, all patients received four consecutive daily sessions of low-level laser therapy, beginning 24 hours after the surgery. Intraoral applications using the diode laser with 660 nm wavelength in the continuous scan mode were performed covering the entire surgical area, which was divided into four quadrants, each of 1 cm2 area at a distance of 1 cm. The energy applied at each point was 5 J/cm2 during 8 seconds. [Results] The swelling and interincisal opening returned to normal 24 hours after the first low-level laser therapy application (Friedman test). Moreover, the pain intensity was reduced on the third postoperative day, according to the Friedman test. [Conclusion] Low-level laser therapy (660 nm), at the dosimetry used in this study, was effective in reducing postoperative pain and swelling following oral surgery. PMID:26180289
Shir, Y; Raja, S N; Frank, S M
Although preemptive analgesia has been shown to decrease postinjury pain in animals, studies in humans have provided controversial results. The authors studied whether surgical epidural anesthesia with local anesthetics could affect postoperative pain and analgesic demands, when compared with general anesthesia. Male patients scheduled for radical retropubic prostatectomy were randomly assigned to receive epidural anesthesia only (EA, n = 34), combined epidural and general anesthesia (EG, n = 32), or general anesthesia only (GA, n = 30). A lumbar epidural catheter was inserted and tested in all patients. In the EA group, an induction dose of 0.25 ml/kg epidural bupivacaine (0.5%) was followed during surgery by a continuous infusion of 0.1 ml.kg-1.h-1 0.125% bupivacaine. In the EG group, 0.2 ml/kg epidural bupivacaine (0.5%) was injected after induction of general anesthesia but before surgery, followed by epidural infusion of 0.1 ml.kg-1.h-1 0.125% bupivacaine. In the GA group, anesthesia was maintained with morphine, isoflurane, and N2O. Epidural patient-controlled analgesia (PCA) was provided with bupivacaine and fentanyl for all patients in the postoperative period. Postoperative pain scores and analgesic requirements were examined and compared between groups every 4-8 h for 3-5 postoperative days. Intraoperatively, EA patients received significantly more epidural bupivacaine than EG patients (129 +/- 6 mg vs. 98 +/- 6 mg, respectively. Recovery room median residual sensory level in EA patients (T6 +/- 2) was significantly higher than in EG patients (T10 +/- 2). PCA demand was greater in the GA and EG groups when compared with the EA group in postoperative days 2 (126 +/- 9 ml, 112 +/- 9 ml, 90 +/- 6 ml, respectively; P = 0.01) and 3 (89 +/- 10 ml, 83 +/- 9 ml, 48 +/- 5 respectively; P = 0.005). There was no difference in PCA demand between the GA and EG groups in the postoperative period. No significant clinical differences in postoperative mean pain scores
de Oliveira Junior, José Oswaldo; de Freitas, Milena Fernandes; Bullara de Andrade, Carolina; Chacur, Marucia; Ashmawi, Hazem Adel
Tramadol is a drug used to treat moderate to severe pain. It is known to present a peripheral effect, but the local mechanisms underlying its actions remain unclear. The role of peripheral opioid receptors in postoperative pain is not well understood. In the present study, we examined the peripheral opioid receptors to determine the local effect of tramadol in a plantar incision pain model. Rats were subjected to plantar incision and divided into four groups on postoperative day (POD) 1: SF_SF, 0.9% NaCl injected into the right hindpaw; SF_TraI, 0.9% NaCl and tramadol injected into the right hindpaw; SF_TraC, 0.9% NaCl and tramadol injected into the contralateral hindpaw; and Nal_Tra, naloxone and tramadol injected into the ipsilateral hindpaw. To determine the animals’ nociceptive threshold, mechanical hyperalgesia was measured before incision, on POD1 before treatment and at 15, 30, 45, and 60 minutes after the incision. The same procedure was repeated on the POD2. The expression levels of μ-opioid receptor (MOR) and δ-opioid receptor (DOR) were obtained through immunoblotting assays in the lumbar dorsal root ganglia (L3–L6) in naïve rats and 1, 2, 3, and 7 days after the incision. Our results showed that the plantar incision was able to cause an increase in mechanical hyperalgesia and that tramadol reversed this hyperalgesia on POD1 and POD2. Tramadol injections in the contralateral paw did not affect the animals’ nociceptive threshold. Naloxone was able to antagonize the tramadol effect partially on POD1 and completely on POD2. The DOR expression increased on POD2, POD3, and POD7, whereas the MOR expression did not change. Together, our results show that tramadol promoted a local analgesic effect in the postoperative pain model that was antagonized by naloxone in POD2, alongside the increase of DOR expression. PMID:27799813
Hong, Jin Pyo; Nam, Sang Min; Im, Chan Young; Yoon, Sangchul; Kim, Tae-Im; Kim, Eung Kweon; Seo, Kyoung Yul
To investigate changes in the pain-suppressing potency of 2 preoperatively applied topical nonsteroidal antiinflammatory drugs (NSAIDs) after photorefractive keratectomy (PRK) using a time-serial pain-scoring system. Saeyan Eye Center, Seoul, South Korea. Comparative case series. Ninety-four patients were randomly assigned to 2 groups: ketorolac group (ketorolac 0.5% in 1 eye and ofloxacin 0.3% in the other eye) and diclofenac group (diclofenac 0.1% in 1 eye and ofloxacin 0.3% in the other eye). One drop of each ophthalmic drug was applied 3 times to each eye 30 minutes before PRK. No other NSAID or steroid was prescribed until 4 days after PRK. The patients were asked to score the postoperative pain in each eye with a visual analog scale at 6, 18, 24, 36, 48, 72, and 96 hours. The natural peak of pain was located between 24 and 36 hours. Initially, the degree of pain reduction was constant for both NSAIDs; it dropped after 24 hours and 36 hours in the ketorolac group and the diclofenac group, respectively. The postoperative time-serial pattern of the pain score changed in the diclofenac group but not in the ketorolac group compared with the pattern in the ofloxacin-treated eye. The visual outcome was not affected by either NSAID, and significant complications were not noticed for a mean of 7 months. The duration and pattern of the action may vary according to types of NSAIDs. Preemptive topical diclofenac 0.1% was a safe and effective method for post-PRK pain control. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
Müller, M; Burkhardt, J; Borchardt, E; Büttner-Janz, K
Recent studies for postoperative pain relief after arthroscopy by intraarticular morphine or bupivacaine showed controversial results. The aim of the study was to evaluate the analgesic effect of intraarticular morphine and ropivacaine. 135 patients were randomized into 9 groups (n=15) after standardized knee-arthroscopy. They received either 1 mg or 5 mg morphine or 150 mg ropivacaine or a combination of 5 mg morphine and 75 mg ropivacaine. Drains were opened either after 10 or 30 minutes. A control-group received isotonic saline. Pain was assesed 1 h and 4 h after surgery, at 8 pm on the day of the operation and at 8am and 4 pm the following two days by a VAS scale. Tramadol consumption as rescue medication was registred. Ropivacaine showed the best pain relief after surgery. After 24 h the pain intensity approximated in all groups and after 48 h there was no difference. Tramadol consumption was highest in the control group and lowest in the ropivacaine group (p<0,05). Ropivacaine showed better pain reduction than morphine. An influence of the time, when drains were opened, could only be demostrated for the 75 mg ropivacain combination group. Intraarticular ropivacaine following elective knee-arthroscopy reduces postoperative analgetic consumption significantly and improves patient comfort.
Pekcan, Zeynep; Koc, Bahattin
To investigate the analgesic and side effects of epidural morphine or a fentanyl patch after ovariohysterectomy in dogs. Prospective, randomized clinical study. Twenty female mongrel dogs undergoing ovariohysterectomy. The dogs were allocated to one of two groups: epidural morphine or transdermal fentanyl patch. Anaesthesia was induced with propofol and maintained with isoflurane. Morphine (0.1 mg kg(-1)) was administered epidurally in the epidural morphine group and a transdermal fentanyl patch was applied 24 hours before the operation in the fentanyl patch group. The heart rate, respiratory rate, body temperature, plasma cortisol concentration, and sedation and analgesia scores were recorded during the 24 hour post-operative period. Adverse effects such as vomiting, anorexia, skin reactions, urinary retention, and time to start licking the surgical site were also recorded. p<0.05 was considered significant. Statistical analyses utilized anova for repeated measures, Friedman tests, Mann-Whitney U-tests and independent sample t-tests as relevant. Pain scores were lower in the epidural group than in the fentanyl group at all post-operative times. The dogs in the epidural morphine group were calm and relaxed, whereas discomfort and vocalization were recorded in the fentanyl patch group. The sedation scores were higher in the fentanyl patch group throughout the 12 hour period. Salivation and anorexia lasted longer in the fentanyl patch group than in the epidural morphine group. Plasma cortisol concentrations were high in the early post-operative period in both groups. The fentanyl patch group had higher cortisol concentrations than the epidural morphine group. Slight erythema was recorded in two dogs when the patches were removed. Epidurally administered morphine provided better analgesia and caused fewer adverse effects than the fentanyl patch after ovariohysterectomy in dogs. © 2010 The Authors. Veterinary Anaesthesia and Analgesia © 2010 Association of Veterinary
Acosta, Alinne Dalla-Porta; Gomar, Carmen; Correa-Natalini, Claudio; Bopp, Simone; Polydoro, Alexandre; Sala-Blanch, Xavier
To evaluate the analgesic and adverse effects of epidurally administered levogyral (S[+]) ketamine alone or in combination with morphine on intraoperative and postoperative pain in dogs undergoing ovariohysterectomy. 30 dogs scheduled for ovariohysterectomy. Dogs were randomly allocated to 1 of 3 groups. Dogs in group 1 received S(+) ketamine (1 mg/kg), dogs in group 2 received S(+) ketamine (0.5 mg/kg) and morphine (0.05 mg/kg), and dogs in group 3 received S(+) ketamine (1 mg/kg) and morphine (0.025 mg/kg). The skin was incised 15 minutes after epidural administration of analgesics. Heart rate (HR), respiratory rate (RR), systolic blood pressure (SBP), oxygen saturation as measured by pulse oximetry, and arterial blood gases were obtained before anesthesia, 15 minutes after epidural administration of analgesics, 15 and 30 minutes after initiation of surgery, and at the end of surgery. During the intraoperative period, an increase of > or =20% in baseline values for HR, RR, and SBP was considered a sign of intraoperative pain. Signs of pain and adverse effects were assessed at 2, 4, and 8 hours postoperatively. There were no significant differences in intraoperative or postoperative measurements among the 3 groups. No dogs had intraoperative signs of pain. Mean postoperative pain assessment scores were <3.5 in all 3 groups. Salivation was the most frequent adverse effect in dogs in groups 1 and 3, and sedation occurred more frequently in dogs in groups 2 and 3. All 3 analgesic regimens provided good respiratory and cardiovascular stability intraoperatively and adequate postoperative analgesia with minimal adverse effects.
Sousa, Angela Maria; Ashmawi, Hazem Adel
Tramadol is known as a central acting analgesic drug, used for the treatment of moderate to severe pain. Local analgesic effect has been demonstrated, in part due to local anesthetic-like effect, but other mechanisms remain unclear. The role of peripheral opioid receptors in the local analgesic effect is not known. In this study, we examined role of peripheral opioid receptors in the local analgesic effect of tramadol in the plantar incision model. Young male Wistar rats were divided into seven groups: control, intraplantar tramadol, intravenous tramadol, intravenous naloxone-intraplantar tramadol, intraplantar naloxone-intraplantar tramadol, intravenous naloxone-intravenous tramadol, and intravenous naloxone. After receiving the assigned drugs (tramadol 5mg, naloxone 200 μg or 0.9% NaCl), rats were submitted to plantar incision, and withdrawal thresholds after mechanical stimuli with von Frey filaments were assessed at baseline, 10, 15, 30, 45 and 60 min after incision. Plantar incision led to marked mechanical hyperalgesia during the whole period of observation in the control group, no mechanical hyperalgesia were observed in intraplantar tramadol group, intraplantar naloxone-intraplantar tramadol group and intravenous naloxone-intraplantar tramadol. In the intravenous tramadol group a late increase in withdrawal thresholds (after 45 min) was observed, the intravenous naloxone-intravenous tramadol group and intravenous naloxone remained hyperalgesic during the whole period. Tramadol presented an early local analgesic effect decreasing mechanical hyperalgesia induced by plantar incision. This analgesic effect was not mediated by peripheral opioid receptors. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
Dereli, Necla; Tutal, Zehra Baykal; Babayigit, Munire; Kurtay, Aysun; Sahap, Mehmet; Horasanli, Eyup
Postoperative pain and nausea/vomitting (PNV) are common in laparoscopic cholecystectomy patients. Sympatholytic agents might decrease requirements for intravenous or inhalation anesthetics and opioids. In this study we aimed to analyze effects of esmolol on intraoperative anesthetic-postoperative analgesic requirements, postoperative pain and PNV. Sixty patients have been included. Propofol, remifentanil and vecuronium were used for induction. Study groups were as follows; I - Esmolol infusion was added to maintenance anesthetics (propofol and remifentanil), II - Only propofol and remifentanil was used during maintenance, III - Esmolol infusion was added to maintenance anesthetics (desflurane and remifentanil), IV - Only desflurane and remifentanil was used during maintenance. They have been followed up for 24h for PNV and analgesic requirements. Visual analog scale (VAS) scores for pain was also been evaluated. VAS scores were significantly lowest in group I (p=0.001-0.028). PNV incidence was significantly lowest in group I (p=0.026). PNV incidence was also lower in group III compared to group IV (p=0.032). Analgesic requirements were significantly lower in group I and was lower in group III compared to group IV (p=0.005). Heart rates were significantly lower in esmolol groups (group I and III) compared to their controls (p=0.001) however blood pressures were similar in all groups (p=0.594). Comparison of esmolol groups with controls revealed that there is a significant decrease in anesthetic and opioid requirements (p=0.024-0.03). Using esmolol during anesthetic maintenance significantly decreases anesthetic-analgesic requirements, postoperative pain and PNV. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.
Oral, Ebru Gelici; Hanci, Ayse; Ulufer Sivrikaya, Gulcihan; Dobrucali, Hale; Turkoglu Kilinc, Leyla
Arthroscopic knee surgery is commonly performed as an outpatient procedure and is often associated with postoperative pain. We aimed to compare the effects of intra-articular levobupivacaine-tenoxicam-tramadol and levobupivacaine-tenoxicam-morphine combinations on postoperative pain in patients undergoing elective arthroscopic knee surgery. A total of 90 ASA I-II patients undergoing elective arthroscopic meniscectomy under general anesthesia were enrolled. The participants were randomly allocated to three groups to receive the following intra-articular medications after completion of the surgery and before deflation of the tourniquet: Group S, 20 mL of saline; Group T, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 100 mg of tramadol in 20 mL saline; and Group M, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 4 mg of morphine in 20 mL saline. Visual analogue scale values at rest (VASr) and at active flexion of knee (VASa) at postoperation hours 1, 2, 4, 8, 12, and 24, duration of analgesia, total analgesic consumption, and number of rescue analgesia at 24 hours were evaluated. VASr and VASa were significantly higher in group S in comparison to other groups (P < 0.05). Duration of analgesia was significantly longer in Group T and Group M than in Group S (P < 0.05). The difference between group T and group M was also significant (P < 0.05). Number of rescue analgesia and total analgesic consumption at postoperative hour 24 was significantly fewer in group M compared with other groups (P < 0.05). Intra-articular levobupivacaine-tenoxicam-morphine combination provides effective pain relief, longer analgesic duration, and less analgesic requirement when compared with intra-articular levobupivacaine-tenoxicam-tramadol combination and saline after knee arthroscopic surgery.
Oral, Ebru Gelici; Hanci, Ayse; Ulufer Sivrikaya, Gulcihan; Dobrucali, Hale; Turkoglu Kilinc, Leyla
Background: Arthroscopic knee surgery is commonly performed as an outpatient procedure and is often associated with postoperative pain. Objectives: We aimed to compare the effects of intra-articular levobupivacaine-tenoxicam-tramadol and levobupivacaine-tenoxicam-morphine combinations on postoperative pain in patients undergoing elective arthroscopic knee surgery. Materials and Methods: A total of 90 ASA I-II patients undergoing elective arthroscopic meniscectomy under general anesthesia were enrolled. The participants were randomly allocated to three groups to receive the following intra-articular medications after completion of the surgery and before deflation of the tourniquet: Group S, 20 mL of saline; Group T, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 100 mg of tramadol in 20 mL saline; and Group M, 35 mg of levobupivacaine, 20 mg of tenoxicam, and 4 mg of morphine in 20 mL saline. Visual analogue scale values at rest (VASr) and at active flexion of knee (VASa) at postoperation hours 1, 2, 4, 8, 12, and 24, duration of analgesia, total analgesic consumption, and number of rescue analgesia at 24 hours were evaluated. Results: VASr and VASa were significantly higher in group S in comparison to other groups (P < 0.05). Duration of analgesia was significantly longer in Group T and Group M than in Group S (P < 0.05). The difference between group T and group M was also significant (P < 0.05). Number of rescue analgesia and total analgesic consumption at postoperative hour 24 was significantly fewer in group M compared with other groups (P < 0.05). Conclusions: Intra-articular levobupivacaine-tenoxicam-morphine combination provides effective pain relief, longer analgesic duration, and less analgesic requirement when compared with intra-articular levobupivacaine-tenoxicam-tramadol combination and saline after knee arthroscopic surgery. PMID:26161321
Mahler, D L; Forrest, W H
Because of discrepancies in the estimates of the relative analgesic potencies of hydromorphone and morphine, the drugs were compared in two four-point, double-blind bioassays. In the first study, hydromorphone, 1 and 2 mg, was compared with morphine, 5 and 10 mg, in 31 postoperative patients; in the second, hydromorphone, 0.5 and 1 mg, was compared with morphine, 5 and 10 mg, in 112 postoperative patients. Subjective responses to nurse-observer questions were used to quantitate analgesia for postoperative pain. Hydromorphone is more potent than commonly believed: approximately 0.9 to 1.2 mg is equianalgesic with 10 mg of morphine, with a similar incidence of side effects.
Khezri, Marzieh Beigom; Tahaei, Elham; Atlasbaf, Amir Hossein
To compare the analgesic efficacy of intrathecal Ketamine and fentanyl added to bupivacaine in patients undergoing cesarean section. Ninety patients 18-40 years old were recruited in a prospective double-blinded, randomized way. Spinal anesthesia was performed in the three groups by using bupivacaine 10mg combined with 0.1mg/kg ketamine in group K, bupivacaine 10mg combined with 25 µg fentanyl in group F and bupivacaine 10mg combined 0.5 ml distilled water in group P. The time to first analgesic request, analgesic requirement in the first 24 hours after surgery, sensory and motor blockade onset time, duration of sensory and motor blockade, the incidence of adverse effects were recorded. The mean time to first analgesic request was longer in group K (296.80 ± 32.46) compared to group F (277.87 ± 94.25) and group P (235.43 ± 22.35). The difference between group K and F (P = 0.504) was not significant but the difference between group K and group P (P <0.001) and group F and group P (P = 0.042) was significant. Addition of ketamine or fentanyl to spinal bupivacaine were equally effective in pain control after cesarean section and therefore, based on the specific conditions of patients, ketamine at concentrations mentioned earlier, could be a proper alternative to achieve postoperative analgesia
Flatters, Sarah J L
Various common surgeries such as thoracotomy and inguinal hernia repair involve essential prolonged tissue retraction, often causing persistent postoperative pain. A new model was developed to mimic this clinical scenario, whereby skin/muscle incision and retraction (SMIR) in the medial thigh evoked persistent postoperative pain (Flatters (2008) [Pain 135:119-130]). This study examines the response of SMIR-evoked mechanical hypersensitivity to analgesic standards commonly used as positive controls in behavioural pain studies. Rats were anaesthetised, the skin and superficial muscle of the medial thigh was then incised and retracted for 1h. In separate experiments, morphine, gabapentin and MK-801 were intraperitoneally administered to SMIR-operated rats, at maximally tolerated doses, on postoperative day 9-13. Mechanical hypersensitivity was measured by withdrawal responses to von Frey stimulation of the plantar hindpaws. Morphine (6mg/kg) and gabapentin (100mg/kg) elicited an almost complete reversal of SMIR-evoked mechanical hypersensitivity. In contrast, MK-801 (0.1mg/kg) did not affect SMIR-evoked mechanical hypersensitivity. Contralateral hindpaw responses to von Frey stimulation were unaffected by SMIR surgery or any drug treatment. In conclusion, the SMIR model displays persistent mechanical hypersensitivity that is reversible by morphine or gabapentin treatment. As previously demonstrated, SMIR-evoked pain is not driven by neuronal damage and these data show that NMDA receptor activation does not play a role in the maintenance of SMIR-evoked pain. This study further demonstrates the value of the SMIR model as a tool to understand persistent postoperative/postsurgical pain mechanisms and evaluate potential treatments.
Geng, Wujun; Hong, Wandong; Wang, Junlu; Dai, Qinxue; Mo, Yunchang; Shi, Kejian; Sun, Jiehao; Qin, Jinling; Li, Mei; Tang, Hongli
Our present study tested whether flurbiprofen axetil could reduce perioperative sufentanil consumption and provide postoperative analgesia with decrease in emergency agitation and systemic proinflammatory cytokines release. Ninety patients undergoing tangential excision surgery were randomly assigned to three groups: (1) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 μg/kg sufentanil and 10 mL placebo by patient-controlled analgesia (PCA) pump, (2) preoperative dose of 100 mg flurbiprofen axetil and a postoperative dose of 2 μg/kg sufentanil and 100 mg flurbiprofen axetil by PCA pump, and (3) 10 mL placebo and a postoperative dose of 2 μg/kg sufentanil and 10 mL placebo by PCA pump. Preoperative administration of flurbiprofen axetil decreased postoperative tramadol consumption and the visual analog scale at 4, 6, 12, and 24 h after surgery, which were further decreased by postoperative administration of flurbiprofen axetil. Furthermore, flurbiprofen axetil attenuated emergency agitation score and Ramsay score at 0, 5, and 10 min after extubation and reduced the TNF-α and interleukin- (IL-) 6 levels at 24 and 48 h after the operation. Flurbiprofen axetil enhances analgesic effects of sufentanil and attenuates emergence agitation and systemic proinflammation in patients undergoing tangential excision surgery.
Tyler, Matthew A; Lam, Kent; Ashoori, Faramarz; Cai, Chunyan; Kain, Joshua J; Fakhri, Samer; Citardi, Martin J; Cattano, Davide; Luong, Amber
Intravenous acetaminophen is a commonly prescribed analgesic for the prevention and treatment of postsurgical pain. Its efficacy in the context of endoscopic sinus surgery (ESS) has yielded mixed results. To compare the efficacy of perioperative intravenous acetaminophen (IVAPAP) with that of placebo in improving early postoperative pain after endoscopic sinus surgery (ESS). A prospective, randomized clinical trial including 62 patients undergoing ESS for chronic rhinosinusitis in a single tertiary referral hospital. Participants were randomized to receive 1 g of IVAPAP or 100 mL of placebo consisting of saline infusions immediately before the start of surgery and 4 hours after the initial dose. The primary outcome was postoperative pain measured by visual analog scale (VAS) scores up to 24 hours after surgery by blinded observers. Secondary endpoints included postoperative opioid (intravenous and oral) use and adverse events in the 24-hour postoperative period. Of the 62 enrolled adult participants, 60 were randomized (31 to IVAPAP intervention and 29 to placebo). The mean (SD) age of participants was 53.7 (14.7) years and 35 (58%) of the participants were men and 25 (42%) were women. Within the first hour, mean pain scores were reduced in the IVAPAP group compared with the control group, reaching a maximum difference of 7.7 mm on a VAS scale favoring the treatment group with a true difference possibly as high as 22 mm, and the data are compatible with a clinically meaningful difference. At 12- and 24-hours, average pain scores were less in the placebo group and the data are compatible with a clinically meaningful difference of 5.8 (-5.2 to 16.8) and 8.2 (-1.9 to 18.4), respectively, favoring the placebo group. However, at all time points the CIs included the null value and were wide, thus preventing definitive conclusions. Inspection of the secondary outcomes favored IVAPAP, but the wide range of the CIs and inclusion of the null value prevent definitive
Intraoperative and postoperative anaesthetic and analgesic effect of multipoint transcutaneous electrical acupuncture stimulation combined with sufentanil anaesthesia in patients undergoing supratentorial craniotomy.
Liu, Xing; Li, Shuqin; Wang, Baoguo; An, Lixin; Ren, Xiujun; Wu, Haifeng
To investigate the anaesthetic and analgesic effect of multipoint transcutaneous electrical acupuncture stimulation (TEAS) during supratentorial tumour resection for postoperative recovery and side effects. In a blinded clinical trial, 92 patients scheduled for supratentorial craniotomy under general anaesthesia were randomly allocated into either a multipoint TEAS (n=46) or a sham TEAS group (n=46). All patients received total intravenous anaesthesia (TIVA) with propofol and sufentanil. The target concentration of sufentanil was adjusted and recorded according to mean arterial pressure (MAP), heart rate (HR) and bispectral index (BIS). Patients in the TEAS group received TEAS 30 min before anaesthesia induction and this was maintained throughout the operation at four pairs of acupuncture points. Postoperative pain, recovery and side effects were evaluated. Eighty-eight patients completed the study. Continuous monitoring of MAP, HR and BIS showed stable values with no significant differences between the two groups (p>0.05). Sufentanil target plasma concentration in TEAS patients was significantly lower at some time points during supratentorial craniotomy, and total sufentanil consumption was significantly higher in the sham group (p<0.05). Postoperative recovery and pain were significantly improved by TEAS (p<0.001), without the postoperative side effects. Multipoint TEAS at both proximal and distal points combined with TIVA can significantly decrease intraoperative sufentanil requirements, increase pain relief on postoperative day 1 and improve postoperative recovery of patients during supratentorial tumour resection, with no significant increase of side effects. These findings suggest that multipoint TEAS may be clinically effective as an adjunct to analgesia in intraoperative anaesthesia and postoperative pain treatment and may speed recovery. Chinese Clinical Trial Registry (registration number ChiCTR-TRC-10001078). Published by the BMJ Publishing Group Limited
Yadav, Ghanshyam; Jain, Gaurav; Samprathi, Abhishek; Baghel, Annavi; Singh, Dinesh Kumar
Background and Aims: Poorly managed acute postoperative pain may result in prolonged morbidity. Various pharmacotherapies have targeted this, but research on an ideal preemptive analgesic continues, taking into account drug-related side effects. Considering the better tolerability profile of tapentadol, we assessed its role as a preemptive analgesic in the reduction of postoperative analgesic requirements, after laparoscopic cholecystectomy. Material and Methods: In a prospective-double-blinded fashion, sixty patients posted for above surgery, were randomized to receive tablet tapentadol 75 mg (Group A) or starch tablets (Group B) orally, an hour before induction of general anesthesia. Perioperative analgesic requirement, time to first analgesia, pain, and sedation score were compared for first 24 h during the postoperative period and analyzed by one-way analysis of variance test. A P < 0.05 was considered significant. Results: Sixty patients were analyzed. The perioperative analgesic requirement was significantly lower in Group A. Verbal numerical score was significantly lower in Group A at the time point, immediately after shifting the patient to the postanesthesia care unit. Ramsay sedation scores were similar between the groups. No major side effects were observed except for nausea and vomiting in 26 cases (10 in Group A, 16 in Group B). Conclusion: Single preemptive oral dose of tapentadol (75 mg) is effective in reducing perioperative analgesic requirements and acute postoperative pain, without added side effects. It could be an appropriate preemptive analgesic, subjected to future trials concentrating upon its dose-response effects. PMID:28096581
Bali, Cagla; Ergenoglu, Pinar; Ozmete, Ozlem; Akin, Sule; Ozyilkan, Nesrin Bozdogan; Cok, Oya Yalcin; Aribogan, Anis
Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18(th) hour on movement (p<0.05). The median time to the first demand of PCA was shorter in Group N compared with Group NC (p<0.001). Meperidine consumption was higher in Group N compared with Group NC (p<0.001). There was no difference between groups with respect to side effects (p>0.05). The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.
Bali, Cagla; Ergenoglu, Pinar; Ozmete, Ozlem; Akin, Sule; Ozyilkan, Nesrin Bozdogan; Cok, Oya Yalcin; Aribogan, Anis
Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18(th) hour on movement (p<0.05). The median time to the first demand of PCA was shorter in Group N compared with Group NC (p<0.001). Meperidine consumption was higher in Group N compared with Group NC (p<0.001). There was no difference between groups with respect to side effects (p>0.05). The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
Raichle, Katherine A; Osborne, Travis L; Jensen, Mark P; Ehde, Dawn M; Smith, Douglas G; Robinson, Lawrence R
The current study examined the relationship between preoperative anxiety and acute postoperative phantom limb pain (PLP), residual limb pain (RLP), and analgesic medication use in a sample of persons undergoing lower limb amputation. Participants included 69 adults admitted to a large level 1 trauma hospital for lower limb amputation. Participants' average pain and anxiety during the previous week were assessed before amputation surgery. RLP, PLP, and analgesic medication use were measured on each of the 5 days following amputation surgery. Results of partial-order correlations indicated that greater preoperative anxiety was significantly associated with greater ratings of average PLP for each of the 5 days following amputation surgery, after controlling for preoperative pain ratings and daily postoperative analgesic medication use. Partial correlation values ranged from 0.30 to 0.62, indicating medium to large effects. Preoperative anxiety was also significantly associated with ratings of average RLP only on postoperative day 1, after controlling for preoperative pain ratings and daily postoperative analgesic medication use (r=0.34, P<0.05). Correlations between preoperative anxiety and daily postoperative analgesic medication dose became nonsignificant when controlling for preamputation and postamputation pain ratings. These findings suggest that anxiety may be a risk factor for acute postamputation PLP and RLP, and indicate that further research to examine these associations is warranted. If replicated, the findings would support research to examine the extent to which modifying preoperative anxiety yields a reduction in postoperative acute PLP and RLP.
Effect of adding intrathecal morphine to a multimodal analgesic regimen for postoperative pain management after laparoscopic bariatric surgery: a prospective, double-blind, randomized controlled trial
El Sherif, Fatma Adel; Othman, Ahmed Hassan; Abd El-Rahman, Ahmad Mohammad; Taha, Osama
Background: Pain control after bariatric surgery is a major challenge. Our objective was to study the efficacy and safety of intrathecal (IT) morphine 0.3 mg added to bupivacaine 0.5% for postoperative pain after laparoscopic bariatric surgery. Methods: After local ethics committee approval, 100 morbidly obese patients scheduled for laparoscopic bariatric surgery were enrolled in this study. Patients were randomly assigned into two groups: Group I received IT 0.3 mg morphine (0.3 mL) added to 1.2 mL of bupivacaine 0.5%; Group II received IT 0.3 mL saline added to 1.2 mL of bupivacaine 0.5%, immediately before induction of general anaesthesia. For both groups, 60 mg ketorolac and 1000 mg paracetamol were infused 30 minutes before the end of surgery. After wound closure, 20 mL bupivacaine 0.25% was infiltrated at wound edges. Results: Visual Analogue Scale (VAS) score was significantly lower in group I immediately, 30 minutes and 1 hour postoperatively. Time to first ambulation, return of intestinal sounds and hospital stay were shorter in group I than group II (p < 0.05); total morphine consumption was significantly lower in group I than group II (p < 0.05). Sedation score was significantly higher in group I immediately postoperatively, while at 30 minutes, 1, 2 and 6 hours postoperatively sedation scores were significantly higher in group II. Itching was significantly higher in group I. Conclusion: The addition of IT morphine to a multimodal analgesic regimen after laparoscopic bariatric surgery was an effective and safe method that markedly reduced postoperative pain, systemic opioid consumption and length of hospital stay. PMID:27867510
Rantala, Maija; Hartikainen, Sirpa; Kvist, Tarja; Kankkunen, Päivi
To describe the analgesic use in hip fracture patients with dementia during the first two postoperative days as reported by nurses. Nurses play a pivotal role in treating postoperative pain in patients with dementia and monitoring the effects of administered analgesics. Cross-sectional descriptive questionnaire study in seven university hospitals and 10 central hospitals in Finland. The study was conducted from March until May in 2011 in Finland. For this analysis, the focus was on the sample of nurses (n = 269) who were working in orthopaedic units. Analgesics were classified according to the Anatomical Therapeutic Chemical Classification System. Nonparametric tests were applied to find out the significant differences between analgesic use and different hospitals. Paracetamol and strong opioids administered orally or parenterally seemed to be the most typical of postoperatively used types of analgesics in patients with dementia. Nonsteroidal anti-inflammatory analgesics and weak opioids were also commonly reported to be in use. There were no statistically significant differences between hospitals in typical daily doses. The majority of the nurses reported that the primary aim of postoperative pain management in hip fracture patients with dementia was 'slight pain, which does not prevent normal functioning' (72%). The pharmacological postoperative pain treatment in acute care was commonly based on the use of strong opioids and paracetamol in hip fracture patients with dementia. The reported use of transdermal opioids and codeine combination warrants further examination. Further studies are also needed to find out whether the pain is appropriately and adequately treated. Transdermal opioids and codeine combination may not be relevant analgesics for acute pain management in older adults. It is important to create a balance between sufficient pain relief and adverse effects of analgesics to allow early mobilisation and functional recovery. © 2014 John Wiley & Sons
Chaparro, Luis E; Lezcano, Wilson; Alvarez, Hernan D; Joaqui, William
The efficacy of non-narcotic analgesics is mostly supported by randomized, placebo-controlled trials with no comparison with ordinary practice. Additionally, systematic reviews of these placebo-controlled trials have failed to determine clinically meaningful dose-response effect. In this double-blind, randomized trial, patients undergoing elective inguinal, umbilical or epigastric herniorrhaphy under general anesthesia were assigned to receive 15 mg/kg (D15 group) vs. 40 mg/kg (D40 group) of dipyrone intravenously during surgery. The primary outcome was the incidence of moderate to severe pain with movement during the recovery room phase. The secondary outcomes were morphine consumption, incidence of vomiting, and Ramsay score (sedation scale). One hundred sixty-two patients were enrolled and analyzed for the primary and secondary outcomes. Relative to the D15 group, the D40 group showed a lower incidence of moderate to severe pain in the first 30 minutes (61% and 40%; P value < 0.05); lower cumulative morphine consumption during the recovery period (3.85 vs. 2.55 mg, P value < 0.006) as well as a lower incidence of vomiting (15.8% vs. 2.5%, P value < 0.005). In addition, more cases of sedation were recorded in the D15 group than in the D40 group (17 vs. 10 cases). There were no serious adverse effects attributed to dipyrone in either group. This trial shows a dose-response effect of 40 mg/kg over 15 mg/kg of intravenous dipyrone based on better movement-induced pain control, lower morphine consumption and fewer opioid-related side effects. © 2011 The Authors. Pain Practice © 2011 World Institute of Pain.
Lyritis, G P; Trovas, G
The analgesic activity of salmon calcitonin (subcutaneous or intranasal) has been demonstrated in several prospective clinical trials, in patients suffering different painful skeletal conditions, including recent nontraumatic osteoporotic vertebral fractures. The mechanism of the analgesic effect of calcitonin is not clear. It is possible that specific binding sites for salmon calcitonin exist in the brain. Another explanation is that changes in descending serotonergic modification on the sensory transmission mediated by C afferents contribute to the analgesic effects of calcitonin on pain in osteoporotic patients. From the clinical point of use, the analgesic effect of calcitonin is beneficial throughout the whole period of medical treatment of osteoporotic patients. Salmon calcitonin in a daily dose of 100 IU subcutaneously or 200 IU intranasally reduces dramatically the back pain (p < 0.0005) after a recent osteoporotic vertebral fracture, and promotes the early mobility of patients. The finding that injectable or intranasally administered salmon calcitonin effectively controls severe pain in osteoporotic patients with a recent vertebral fracture, allowing them earlier mobility in combination with a reduction of the urinary hydroxyproline excretion, and a limitation of the considerable bone loss that may occur during prolonged bed rest, make this therapeutic scheme attractive.
Eidy, Mohammad; Fazel, Mohammad Reza; Janzamini, Monir; Haji Rezaei, Mostafa; Moravveji, Ali Reza
Background Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological analgesic method used to control different types of pain. Objectives The aim of this study was to evaluate the effects of preoperative TENS on post inguinal hernia repair pain. Patients and Methods This randomized, double-blind, placebo-controlled clinical trial was performed on 66 male patients with unilateral inguinal hernias who were admitted to the Shahid Beheshti hospital in Kashan, Iran, from April to October 2014. Participants were selected using a convenience sampling method and were assigned to intervention (n = 33) and control (n = 33) groups using permuted-block randomization. Patients in the intervention group were treated with TENS 1 hour before surgery, while the placebo was administered to patients in the control group. All of the patients underwent inguinal hernia repair by the Lichtenstein method, and pain intensity was evaluated at 2, 4, 6, and 12 hours after surgery using a visual analogue scale. Additionally, the amounts of analgesic administered by pump were calculated and compared between the two groups. Results The mean estimated postoperative pain intensity was 6.21 ± 1.63 in the intervention group and 5.45 ± 1.82 in the control group (P = 0.08). In the intervention group pain intensity at 2 and 4 hours after surgery were 3.54 ± 1.48 and 5.12 ± 1.41 (P < 0.001), respectively. In the control group these values were 4.0±1.5 and 4.76 ± 1.39 (P = 0.04), respectively. No significant differences were observed in mean pain intensities at 6 and 12 hours. Conclusions TENS can reduce postoperative pain in the early hours after inguinal hernia repair surgery. PMID:27275401
Eidy, Mohammad; Fazel, Mohammad Reza; Janzamini, Monir; Haji Rezaei, Mostafa; Moravveji, Ali Reza
Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological analgesic method used to control different types of pain. The aim of this study was to evaluate the effects of preoperative TENS on post inguinal hernia repair pain. This randomized, double-blind, placebo-controlled clinical trial was performed on 66 male patients with unilateral inguinal hernias who were admitted to the Shahid Beheshti hospital in Kashan, Iran, from April to October 2014. Participants were selected using a convenience sampling method and were assigned to intervention (n = 33) and control (n = 33) groups using permuted-block randomization. Patients in the intervention group were treated with TENS 1 hour before surgery, while the placebo was administered to patients in the control group. All of the patients underwent inguinal hernia repair by the Lichtenstein method, and pain intensity was evaluated at 2, 4, 6, and 12 hours after surgery using a visual analogue scale. Additionally, the amounts of analgesic administered by pump were calculated and compared between the two groups. The mean estimated postoperative pain intensity was 6.21 ± 1.63 in the intervention group and 5.45 ± 1.82 in the control group (P = 0.08). In the intervention group pain intensity at 2 and 4 hours after surgery were 3.54 ± 1.48 and 5.12 ± 1.41 (P < 0.001), respectively. In the control group these values were 4.0±1.5 and 4.76 ± 1.39 (P = 0.04), respectively. No significant differences were observed in mean pain intensities at 6 and 12 hours. TENS can reduce postoperative pain in the early hours after inguinal hernia repair surgery.
Postoperative analgesic and behavioral effects of intranasal fentanyl, intravenous morphine, and intramuscular morphine in pediatric patients undergoing bilateral myringotomy and placement of ventilating tubes.
Hippard, Helena K; Govindan, Kalyani; Friedman, Ellen M; Sulek, Marcelle; Giannoni, Carla; Larrier, Deidre; Minard, Charles G; Watcha, Mehernoor F
Bilateral myringotomy and placement of ventilating tubes (BMT) is one of the most common pediatric surgical procedures in the United States. Many children who undergo BMT develop behavioral changes in the postanesthesia care unit (PACU) and require rescue pain medication. The incidence of these changes is lower in children receiving intraoperative opioids by the nasal, IM, or IV route compared with placebo. However, there are no data to indicate which route of administration is better. Our study was designed to compare the immediate postoperative analgesic and behavioral effects of 3 frequently used intraoperative techniques of postoperative pain control for patients undergoing BMT under general anesthesia. One hundred seventy-one ASA physical status I and II children scheduled for BMT were randomized into 1 of 3 groups: group 1-nasal fentanyl 2 μg/kg with IV and IM saline placebo; group 2-IV morphine 0.1 mg/kg with nasal and IM placebo; or group 3-IM morphine 0.1 mg/kg with nasal and IV placebo. All subjects received a standardized general anesthetic with sevoflurane, N(2)O, and O(2) and similar postoperative care. The primary end point of the study was the pain scores measured by the Faces, Legs, Activity, Cry, and Consolability (FLACC) scale in the PACU. There were no significant differences in peak FLACC pain among the 3 groups (mean [95% CI] 2.0 [1.2-2.8] for intranasal fentanyl, 2.7 [1.7-3.6] for IV morphine, and 2.9 [2.1-3.7] for IM morphine, respectively). There were no differences in the scores on the Pediatric Anesthesia Emergence Delirium (PAED) scale, incidence of postoperative emergence delirium (PAED score ≥ 12), emesis, perioperative hypoxemia, or need for airway intervention, and postoperative rescue analgesia. There were also no differences in the duration of PACU stay or parental satisfaction among the groups. In this double-blind, double-dummy study, there was no difference in the efficacy of intranasal fentanyl, IM and IV morphine in
Analgesics and ENT surgery. A clinical comparison of the intraoperative, recovery and postoperative effects of buprenorphine, diclofenac, fentanyl, morphine, nalbuphine, pethidine and placebo given intravenously with induction of anaesthesia.
van den Berg, A A; Honjol, N M; Prabhu, N V; Datta, S; Rozario, C J; Muraleedaran, R; Savva, D
1. Vomiting and restlessness following ENT and eye surgery are undesirable, and may be related to the emetic and analgesic effects of any analgesic given to augment anaesthesia during surgery. 2. To rationalise the choice of analgesic for routine ENT surgery we examined the intraoperative, recovery and postoperative effects following the administration of either buprenorphine (3.0 to 4.5 micrograms kg-1), diclofenac (1 mg kg-1), fentanyl (1.5 to 2.0 micrograms kg-1), morphine (0.1 to 0.15 mg kg-1), nalbuphine (0.1 to 0.15 mg kg-1), pethidine (1.0 to 1.5 mg kg-1) or saline (as control) given with the induction of anaesthesia in 374 patients. A standardised anaesthetic technique with controlled ventilation using 0.6-0.8% isoflurane in nitrous oxide and oxygen was employed. The study population constituted 7 similar groups of patients. 3. Intraoperatively, their effects on heart rate and blood pressure, airway pressure and intraocular pressure, were similar. This implies, most surprisingly, that neither their analgesic nor their histamine releasing effects were clinically evident during surgery. By prolonging the time to extubation at the end of anaesthesia, only buprenorphine, fentanyl, morphine and pethidine provided evidence of intraoperative respiratory depression. 4. Postoperatively, buprenorphine was associated with severe respiratory depression, prolonged somnolence, profound analgesia and the highest emesis rate. Diclofenac exhibited no sedative, analgesic, analgesic sparing, emetic or antipyretic effects. Fentanyl provided no sedative or analgesic effects, but was mildly emetic. Morphine provided poor sedation and analgesia, delayed the requirement for re-medication and was highly emetic. Nalbuphine and pethidine produced sedation with analgesia during recovery, a prolonged time to re-medication and a mild emetic effect. None provided evidence, from analysis of postoperative re-medication times and analgesic consumption, of any pre-emptive analgesic effect. 5
Ekblom, A; Hansson, P; Thomsson, M; Thomas, M
Acupuncture was given to patients before (preoperative-acupuncture group, PRE-ACU, n = 25) or after (postoperative-acupuncture group, POST-ACU, n = 25) operative removal of impacted mandibular third molars. Sixty patients did not receive acupuncture and participated as a control group (CG). All patients completed a questionnaire in order to characterize state tension and stress, degrees of neuroticism, extroversion, depression and psychosomatic disorders. We also recorded intraoperative discomfort and pain intensity, postoperative pain intensity and consumption of analgesics for 72 h. The PRE-ACU was significantly more tense following surgery and found the operative procedure more unpleasant than the other two groups. The PRE-ACU further rated intraoperative pain intensity higher than the CG and experienced higher pain intensity immediately postoperatively compared with POST-ACU and CG. Of the PRE-ACU patients 15/24 needed additional local anesthesia intraoperatively while none in the POST-ACU or CG requested extra lidocaine. Postoperatively patients in both PRE- and POST-ACU reported a higher total sum of pain scores (pain intensity) and the PRE-ACU consumed more analgesics compared with the CG. A significantly larger number of patients suffering from "dry socket" (a complication during wound healing) was found in both PRE- and POST-ACU compared with the CG. No correlation was found between assessed personality characteristics and reported postoperative pain/consumption of analgesics in any group and could thus not explain the observed differences between the groups. The reason for our unexpected "negative" findings is unclear but some hypothetical explanations are discussed.
Postoperative analgesic effects of either a constant rate infusion of fentanyl, lidocaine, ketamine, dexmedetomidine, or the combination lidocaine-ketamine-dexmedetomidine after ovariohysterectomy in dogs.
Gutierrez-Blanco, Eduardo; Victoria-Mora, José M; Ibancovichi-Camarillo, José A; Sauri-Arceo, Carlos H; Bolio-González, Manuel E; Acevedo-Arcique, Carlos M; Marin-Cano, Gabriela; Steagall, Paulo Vm
To evaluate the postoperative analgesic effects of a constant rate infusion (CRI) of either fentanyl (FENT), lidocaine (LIDO), ketamine (KET), dexmedetomidine (DEX), or the combination lidocaine-ketamine-dexmedetomidine (LKD) in dogs. Randomized, prospective, blinded, clinical study. Fifty-four dogs. Anesthesia was induced with propofol and maintained with isoflurane. Treatments were intravenous (IV) administration of a bolus at start of anesthesia, followed by an IV CRI until the end of anesthesia, then a CRI at a decreased dose for a further 4 hours: CONTROL/BUT (butorphanol 0.4 mg kg(-1), infusion rate of saline 0.9% 2 mLkg(-1) hour(-1)); FENT (5 μg kg(-1), 10 μg kg(-1) hour(-1), then 2.5 μg kg(-1) hour(-1)); KET (1 mgkg(-1) , 40 μg kg(-1) minute(-1), then 10 μg kg(-1) minute(-1) ; LIDO (2 mg kg(-1), 100 μg kg(-1) minute(-1), then 25 μg kg(-1) minute(-1)); DEX (1 μgkg(-1), 3 μg kg(-1) hour(-1), then 1 μg kg(-1) hour(-1)); or a combination of LKD at the aforementioned doses. Postoperative analgesia was evaluated using the Glasgow composite pain scale, University of Melbourne pain scale, and numerical rating scale. Rescue analgesia was morphine and carprofen. Data were analyzed using Friedman or Kruskal-Wallis test with appropriate post-hoc testing (p < 0.05). Animals requiring rescue analgesia included CONTROL/BUT (n = 8), KET (n = 3), DEX (n = 2), and LIDO (n = 2); significantly higher in CONTROL/BUT than other groups. No dogs in LKD and FENT groups received rescue analgesia. CONTROL/BUT pain scores were significantly higher at 1 hour than FENT, DEX and LKD, but not than KET or LIDO. Fentanyl and LKD sedation scores were higher than CONTROL/BUT at 1 hour. LKD and FENT resulted in adequate postoperative analgesia. LIDO, CONTROL/BUT, KET and DEX may not be effective for treatment of postoperative pain in dogs undergoing ovariohysterectomy. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.
Dionne, Raymond A.; Wirdezk, Peggy R.; Butler, Donald P.; Fox, Philip C.
The analgesic efficacy of two doses of conorphone (20 and 40 mg), a mixed agonist-antagonist analgesic, were compared to two doses of codeine for postoperative pain in the oral surgery model. Each subject received 2 of the 4 possible treatment at two separate sessions in an incomplete block, single crossover design. Both doses of conorphone and the 60 mg dose of codeine were superior to 30 mg of codeine for the various indices of analgesic activity. The 40 mg dose of conorphone resulted in a high incidence of side effects (25/30 subjects) such as drowsiness, dizziness, nausea and vomiting. The low dose of conorphone resulted in side effects similar to 60 mg of codeine with the exception of a greater incidence of drowsiness. These data suggest that while 40 mg of conorphone may not be well tolerated clinically, 20 mg of conorphone may be an alternative to 60 mg of codeine for postoperative pain. PMID:6597688
Moore, R Andrew; Derry, Sheena; McQuay, Henry J; Wiffen, Philip J
Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data. To summarise data from all Cochrane Reviews that have assessed the effects of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery, who have been given a single dose of oral analgesic taken alone. We identified systematic reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single Review Group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews we extracted the number needed to treat (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, the percentage of participants remedicating by 6, 8, 12, or 24 hours, and results for participants experiencing at least one adverse event. The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken.There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130 mg, diflunisal 125 mg, etoricoxib 60 mg
Moore, R Andrew; Derry, Sheena; McQuay, Henry J; Wiffen, Philip J
Background Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data. Objectives To summarise data from all Cochrane Reviews that have assessed the effects of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery, who have been given a single dose of oral analgesic taken alone. Methods We identified systematic reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single Review Group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews we extracted the number needed to treat (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, the percentage of participants remedicating by 6, 8, 12, or 24 hours, and results for participants experiencing at least one adverse event. Main results The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken. There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130
Yektaş, Abdulkadir; Belli, Enver
OBJECTIVE: To compare the postoperative analgesic characteristics and side effects of two different doses of intrathecal dexmedetomidine in combination with hyperbaric bupivacaine, and to evaluate the effects of these combinations on spinal anesthesia. METHODS: After obtaining approval from the local ethics committee, 60 male patients who were undergoing inguinal surgery and were classified as American Society of Anesthesiologists physical status class I were included in the study. The present study was conducted in 2003 in a military hospital with a capacity of 100 beds. The patients were randomly assigned to three groups of 20 patients: group 1, 0.5 mL saline added to 3 mL (15 mg) hyperbaric bupivacaine; and groups 2 and 3, 2 μg dexme-detomidine and 4 μg dexmedetomidine added to 3 mL (15 mg) hyperbaric bupivacaine, respectively. Medications were administered by intrathecal injection in a total volume of 3.5 mL. The postoperative analgesic characteristics, effects on spinal anesthesia and side effects were recorded. RESULTS: Demographic characteristics were similar among the groups. The mean (± SD) time to onset of pain was 220.75±112.7 min in group 1, 371.5±223.5 min in group 2 and 1042.50±366.78 min in group 3. Time to first pain sensation in group 3 was significantly longer than that in groups 1 and 2 (P<0.001). CONCLUSION: Two different doses of dexmedetomidine, an α2-adrenoceptor agonist with analgesic effects, resulted in an increased duration of analgesia and efficacy, decreased postoperative analgesic use and was associated with no notable adverse effects. PMID:24527467
Matsumiya, Lynn C; Sorge, Robert E; Sotocinal, Susana G; Tabaka, John M; Wieskopf, Jeffrey S; Zaloum, Austin; King, Oliver D; Mogil, Jeffrey S
Postoperative pain management in animals is complicated greatly by the inability to recognize pain. As a result, the choice of analgesics and their doses has been based on extrapolation from greatly differing pain models or the use of measures with unclear relevance to pain. We recently developed the Mouse Grimace Scale (MGS), a facial-expression–based pain coding system adapted directly from scales used in nonverbal human populations. The MGS has shown to be a reliable, highly accurate measure of spontaneous pain of moderate duration, and therefore is particularly useful in the quantification of postoperative pain. In the present study, we quantified the relative intensity and duration of postoperative pain after a sham ventral ovariectomy (laparotomy) in outbred mice. In addition, we compiled dose–response data for 4 commonly used analgesics: buprenorphine, carprofen, ketoprofen, and acetaminophen. We found that postoperative pain in mice, as defined by facial grimacing, lasts for 36 to 48 h, and appears to show relative exacerbation during the early dark (active) photophase. We find that buprenorphine was highly effective in inhibiting postoperative pain-induced facial grimacing in mice at doses equal to or lower than current recommendations, that carprofen and ketoprofen are effective only at doses markedly higher than those currently recommended, and that acetaminophen was ineffective at any dose used. We suggest the revision of practices for postoperative pain management in mice in light of these findings. PMID:22330867
The comparison of analgesic effects of various administration methods of diclofenac sodium, transdermal, oral and intramuscular, in early postoperative period in laparoscopic cholecystectomy operations.
Gulcin Ural, Sedef; Yener, Ozlem; Sahin, Hasan; Simsek, Tuncer; Aydinli, Bahar; Ozgok, Aysegul
The aim of this study was to compare the efficacy of oral, intra muscular and transdermal diclofenac sodium for pain treatment in patients undergoing laparoscopic cholecystectomy, and their effect on postoperative opioid consumption. Following informed consent, 90 ASA I-II patients scheduled for laparoscopic cholecystectomy were randomized into three groups. Group PO got oral diclofenac sodium 1 hour before the operation, Group IM 75 mg diclofenac sodium intra muscular and Group TD diclofenac sodium patch 6 hours before the operation. Patients were not premedicated. Routine anaesthesia induction was used. After the operation in post anaesthesia care unit tramadol HCl infusion was delivered by intravenous patient controlled analgesia (iv PCA). Ramsey Sedation Score (RSS), Modified Aldrete's Score System(MASS) and Visual Analog Scale Pain Score (VAS) was used for postoperative evaluation. Postoperative opioid consumption was recorded. Demographic characteristics, intraoperative and postoperative hemodynamics of the patients were similar between groups. Postoperative VAS were lower at all time points in Group IM and Group TD than in Group PO. Lowest Postoperative RSS were in Group IM and the highest were in Group PO, and the difference between groups was significant. There was no significant difference in Postoperative MASS between groups. Postoperative tramadol consumption was statistically different between groups. Tramadol consumption in Group IM and Group TD was lower than Group PO. Postoperative nausea and vomiting was not observed. Local complications related to transdermal and intra muscular applications was not reported. In patients undergoing ambulatory laparoscopic cholecystectomy, a noninvasive application transdermal diclofenac sodium is as effective as intramuscular diclofenac sodium and can be preferred in postoperative pain treatment.
The comparison of analgesic effects of various administration methods of diclofenac sodium, transdermal, oral and intramuscular, in early postoperative period in laparoscopic cholecystectomy operations
Gulcin Ural, Sedef; Yener, Ozlem; Sahin, Hasan; Simsek, Tuncer; Aydinli, Bahar; Ozgok, Aysegul
Objective: The aim of this study was to compare the efficacy of oral, intra muscular and transdermal diclofenac sodium for pain treatment in patients undergoing laparoscopic cholecystectomy, and their effect on postoperative opioid consumption. Methods: Following informed consent, 90 ASA I-II patients scheduled for laparoscopic cholecystectomy were randomized into three groups. Group PO got oral diclofenac sodium 1 hour before the operation, Group IM 75 mg diclofenac sodium intra muscular and Group TD diclofenac sodium patch 6 hours before the operation. Patients were not premedicated. Routine anaesthesia induction was used. After the operation in post anaesthesia care unit tramadol HCl infusion was delivered by intravenous patient controlled analgesia (iv PCA). Ramsey Sedation Score (RSS), Modified Aldrete’s Score System(MASS) and Visual Analog Scale Pain Score (VAS) was used for postoperative evaluation. Postoperative opioid consumption was recorded. Results: Demographic characteristics, intraoperative and postoperative hemodynamics of the patients were similar between groups. Postoperative VAS were lower at all time points in Group IM and Group TD than in Group PO. Lowest Postoperative RSS were in Group IM and the highest were in Group PO, and the difference between groups was significant. There was no significant difference in Postoperative MASS between groups. Postoperative tramadol consumption was statistically different between groups. Tramadol consumption in Group IM and Group TD was lower than Group PO. Postoperative nausea and vomiting was not observed. Local complications related to transdermal and intra muscular applications was not reported. Conclusion: In patients undergoing ambulatory laparoscopic cholecystectomy, a noninvasive application transdermal diclofenac sodium is as effective as intramuscular diclofenac sodium and can be preferred in postoperative pain treatment. PMID:24639839
Effectiveness of Epidural Analgesia, Continuous Surgical Site Analgesia, and Patient-Controlled Analgesic Morphine for Postoperative Pain Management and Hyperalgesia, Rehabilitation, and Health-Related Quality of Life After Open Nephrectomy: A Prospective, Randomized, Controlled Study.
Capdevila, Xavier; Moulard, Sebastien; Plasse, Christian; Peshaud, Jean-Luc; Molinari, Nicolas; Dadure, Christophe; Bringuier, Sophie
There is no widely recognized effective technique to optimally reduce pain scores and prevent persistent postoperative pain after nephrectomy. We compared continuous surgical site analgesia (CSSA), epidural analgesia (EA), and a control group (patient-controlled analgesic morphine) in patients undergoing open nephrectomy. Sixty consecutive patients were randomized to be part of EA, CSSA, or control groups postoperatively for 72 hours. All patients received patient-controlled analgesic morphine, if needed. Hyperalgesia was assessed on the first, second, and third postoperative days. Chronic pain characteristics and quality of life were analyzed at 1 and 3 months. The primary outcome was the pain score at 24 hours. Secondary outcomes were morphine consumption, postoperative rehabilitation, hyperalgesia, chronic pain incidence, and quality-of-life parameters. At 24 hours, mean ± standard deviation pain values at rest (2.4 ± 1.7, 2.2 ± 1.2, and 4.2 ± 1.2, respectively, in EA, CSSA, and control groups, P <.001) and during coughing was lower in the EA and CSSA groups. Total morphine consumption was higher in the control group. Rehabilitation parameters improved sooner in the EA and CSSA groups. Median values of area of hyperalgesia differed at 48 hours between the EA group and the control group (36.4 cm) and (52 cm) (P = .01) and at 72 hours among the EA group, CSSA group, and the control group (40 cm, 39.5 cm, and 59 cm, respectively; P = .002). CSSA reduced the severity of pain and hyperalgesia at 1 month and optimized quality of life 3 months after surgery (role physical scores, P = .005). CSSA and EA significantly improve postoperative analgesia, reduce postoperative morphine consumption, area of wound hyperalgesia, and accelerate patient rehabilitation after open nephrectomy. CSSA significantly reduces the severity of residual pain 1 month after surgery and optimizes quality-of-life parameters 3 months after surgery.
Jain, Ankesh Dilip; Vsm, Ravisankar; Ksn, Siva Bharani; Km, Sudheesh; Tewathia, Nisha
Pain after any surgical procedure is inevitable but can be controlled by administration of analgesics in most cases. Postoperative pain after surgical treatment of mandibular fractures can be treated by nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics. The purpose of this study is to critically compare the postoperative analgesic efficacy of small doses of intravenous TRAMADOL (opioid analgesic) versus LORNOXICAM (NSAID) in patients with mandibular trauma undergoing open reduction and internal fixation (ORIF) and to assess the presence of any adverse effects due to NSAID or opioid use. Forty adult ASA grade I-II patients with mandibular trauma, scheduled for ORIF under general anesthesia in the Department of Oral and Maxillofacial Surgery, College of Dental Sciences, Davangere, were selected for the study. The patients were randomly assigned into a tramadol group (Group T) and a lornoxicam group (Group L) and were administered intravenous tramadol 50 mg and intravenous lornoxicam 8 mg, respectively, at specific postoperative intervals. Pain intensity was quantitatively assessed at the 2nd, 4th, 6th, 12th, and 24th postoperative hours using a visual analog scale of 10 cm. Adverse effects of the analgesics were also recorded and compared. Both the drugs resulted in a significant decrease in pain intensity from 2nd to 24th postoperative hours, but better pain control was observed in Group L at 24th postoperative hour. Only two patients experienced nausea and vomiting in Group T and one patient experienced gastric acidity in Group L. The comparative results clearly demonstrate that pain control by intravenous lornoxicam is significantly better than by intravenous tramadol at 24th postoperative hour after ORIF of mandibular trauma. Side effects produced by both the drugs were minor and had no apparent effect on the study results.
Ryu, Jung-Hee; Yom, Cha Kyong; Kwon, Hyungju; Kim, Kyu Hyung; Choi, June Young; Jung, Jun Woo; Kim, Sung-Won; Oh, Ah-Young
Robotic thyroidectomy (RoT) is frequently performed due to its excellent cosmesis and recovery features. However, postoperative pain in the operating field after RoT remains a concern due to extensive tissue dissection and tension during the operation. The aim of this study was to evaluate the anterior chest pain and the effect of levobupivacaine spraying on postoperative pain control after bilateral axillo-breast approach (BABA) RoT. We randomized 55 adult patients scheduled for BABA RoT into the control group (group C, n = 27) or the levobupivacaine group (group L, n = 28). At the end of surgery, patients in groups C and L were sprayed with the same volume (30 ml) of normal saline and 0.25 % levobupivacaine, respectively, on the flap dissection area. Pain scores, the consumption of patient-controlled analgesia (PCA), and other adverse effects were assessed at 1, 6, 24, and 48 h postoperatively. Patients in group L showed lower pain scores than those of group C at 1 h (50 [0-100] vs. 80 [20-100]; p = 0.004), 6 h (30 [0-90] vs. 70 [30-90]; p < 0.001), 24 h (30 [0-80] vs. 50 [10-80]; p = 0.016) and 48 h (10 [0-80] vs. 30 [10-80]; p < 0.001) postoperatively. PCA consumption of group L was less than that of group C at 6, 24, and 48 h after surgery. There were no significant differences in postoperative nausea-vomiting, headache, or dizziness. Local anesthetic-related adverse effects were not reported. Levobupivacaine spray on the operative field at the end of BABA RoT reduced postoperative pain and PCA consumption without adverse events.
Lojanapiwat, Bannakij; Chureemas, Tanarit; Kittirattarakarn, Pruit
To study the efficacy of peritubal infiltration in postoperative pain following percutaneous nephrolithotomy in general PCNL patients and PCNL patients with supracostal renal access. A total of 105 PCNL patients were randomized into two groups, 53 patients receiving peritubal analgesic infiltration (study group) and 52 patients as the control group. Of these patients, supracostal access was performed in 22 patients of study group and 23 patients of control group. The study group received peritubal injection with 10mL of bupivacain. Postoperative pain as the primary outcome was assessed by using visual analogue scale at 1, 4, 12, 24 and 48 hours postoperatively. The secondary outcomes were the total postoperative morphine usage in 24 hours and time of the first analgesic demand. The average VAS pain at 1 and 4 hours after the operation in the study group were significant lower in the control group (P≤ 0.001 and 0.026). Doses of morphine usage for controlling postoperative pain and the first analgesic demand were significantly lower and longer in study group. Among patients submitted to supracostal access, the average VAS pain at 1 hour after operation in the study group was lower (P=0.018). Doses of morphine usage for controlling postoperative pain also was lower in the study group (P=0.012). The peritubal local anesthetic infiltration is effective in alleviating immediate postoperative pain after percutaneous nephrolithotomy even with supracostal access.
Lojanapiwat, Bannakij; Chureemas, Tanarit; Kittirattarakarn, Pruit
ABSTRACT Objective: To study the efficacy of peritubal infiltration in postoperative pain following percutaneous nephrolithotomy in general PCNL patients and PCNL patients with supracostal renal access. Patients and Methods: A total of 105 PCNL patients were randomized into two groups, 53 patients receiving peritubal analgesic infiltration (study group) and 52 patients as the control group. Of these patients, supracostal access was performed in 22 patients of study group and 23 patients of control group. The study group received peritubal injection with 10mL of bupivacain. Postoperative pain as the primary outcome was assessed by using visual analogue scale at 1, 4, 12, 24 and 48 hours postoperatively. The secondary outcomes were the total postoperative morphine usage in 24 hours and time of the first analgesic demand. Results: The average VAS pain at 1 and 4 hours after the operation in the study group were significant lower in the control group (P≤0.001 and 0.026). Doses of morphine usage for controlling postoperative pain and the first analgesic demand were significantly lower and longer in study group. Among patients submitted to supracostal access, the average VAS pain at 1 hour after operation in the study group was lower (P=0.018). Doses of morphine usage for controlling postoperative pain also was lower in the study group (P=0.012). Conclusion: The peritubal local anesthetic infiltration is effective in alleviating immediate postoperative pain after percutaneous nephrolithotomy even with supracostal access. PMID:26689520
Wolfe, A Marissa; Kennedy, Lucy H; Na, Jane J; Nemzek-Hamlin, Jean A
Tramadol is a centrally acting weak μ opioid agonist that has few of the adverse side effects common to other opioids. Little work has been done to establish an effective analgesic dose of tramadol specific for surgical laparotomy and visceral manipulation in mice. We used general appearance parameters to score positive indicators of pain including posture, coat condition, activity, breathing, and interactions with other mice, activity events (that is, the number of times each mouse stretched up in a 3-min period) used as an indicator of decreased pain, von Frey fibers, and plasma levels of corticosterone to determine whether tramadol at 20, 40, or 80 mg/kg prevented postoperative pain in male and female C57BL/6 mice. A ventral midline laparotomy with typhlectomy was used as a model of postoperative pain. In male mice, none of the markers differed between groups that received tramadol (regardless of dose) and the saline-treated controls. However, general appearance scores and plasma corticosterone levels were lower in female mice that received 80 mg/kg tramadol compared with saline. In summary, for severe postoperative pain after laparotomy and aseptic typhlectomy, tramadol was ineffective in male C57BL/6 mice at all doses tested. Although 80 mg/kg ameliorated postoperative pain in female C57BL/6 mice, this dose is very close to the threshold reported to cause toxic side effects, such as tremors and seizures. Therefore, we do not recommend the use of tramadol as a sole analgesic in this mouse model of postoperative pain. PMID:26224442
Wolfe, A Marissa; Kennedy, Lucy H; Na, Jane J; Nemzek-Hamlin, Jean A
Tramadol is a centrally acting weak μ opioid agonist that has few of the adverse side effects common to other opioids. Little work has been done to establish an effective analgesic dose of tramadol specific for surgical laparotomy and visceral manipulation in mice. We used general appearance parameters to score positive indicators of pain including posture, coat condition, activity, breathing, and interactions with other mice, activity events (that is, the number of times each mouse stretched up in a 3-min period) used as an indicator of decreased pain, von Frey fibers, and plasma levels of corticosterone to determine whether tramadol at 20, 40, or 80 mg/kg prevented postoperative pain in male and female C57BL/6 mice. A ventral midline laparotomy with typhlectomy was used as a model of postoperative pain. In male mice, none of the markers differed between groups that received tramadol (regardless of dose) and the saline-treated controls. However, general appearance scores and plasma corticosterone levels were lower in female mice that received 80 mg/kg tramadol compared with saline. In summary, for severe postoperative pain after laparotomy and aseptic typhlectomy, tramadol was ineffective in male C57BL/6 mice at all doses tested. Although 80 mg/kg ameliorated postoperative pain in female C57BL/6 mice, this dose is very close to the threshold reported to cause toxic side effects, such as tremors and seizures. Therefore, we do not recommend the use of tramadol as a sole analgesic in this mouse model of postoperative pain.
Bali, Cagla; Ozmete, Ozlem; Eker, H Evren; Hersekli, Murat A; Aribogan, Anis
This study evaluated the postoperative analgesic efficacies of fascia iliaca block and periarticular drug injection techniques after TKA (total knee arthroplasty) surgeries. Prospective, randomized clinical trial. University Teaching and Research Center. Seventy-one American Society of Anesthesiologists (ASA) I-III patients between 48 and 70 years of age who underwent total knee arthroplasty were randomized. Tenoxicam (20 mg) was administered intramuscularly to both groups of patients 30 minutes before surgery. Patients were randomized into two groups to receive fascia iliaca block before the induction of anesthesia (Group FI) or periarticular drug injection during the surgery (Group PI). All surgeries were performed under general anesthesia using standard techniques. Postoperative analgesia was provided with patient-controlled intravenous morphine. Total morphine consumption was the primary outcome measure and was recorded postoperatively at 1, 2, 6, 12 and 24 hours. Pain levels at rest and on movement (knee flexion) were evaluated using the Visual Analogue Scale (VAS) and recorded at the same time points. Patients' demographics, rescue analgesic demands, side effects, hemodynamics, and satisfaction scores were also recorded. The groups had similar VAS scores both at rest and on movement (P>.05). However, the amount of cumulative morphine and use at each follow-up period was higher in Group PI (P<.0001). The groups did not differ significantly in rescue analgesic use or side effects, such as nausea/vomiting, hemodynamic variables, and patient satisfaction scores (P>.05). Fascia iliaca block may be used as an alternative method to periarticular injection, and it effectively reduces the amount of morphine used to relieve post-TKA pain. Copyright © 2016 Elsevier Inc. All rights reserved.
Dohoo, S E; Dohoo, I R
Four hundred and seventeen Canadian veterinarians were surveyed to determine their postoperative use of analgesics in dogs and cats following 6 surgical procedures, and to determine their opinions toward pain perception and perceived complications associated with the postoperative use of potent opioid analgesics. Three hundred and seventeen (76%) returned the questionnaire. The percentage of animals receiving analgesics postoperatively ranged from 84% of dogs and 70% of cats following orthopedic surgery to 10% of dogs and 9% of cats following castration. In general, with the exception of orthopedic surgery, roughly equal percentages of dogs and cats received postoperative analgesics. Opioids were used almost exclusively to provide postoperative analgesia, with butorphanol the most commonly administered drug to both dogs and cats. Analgesics were usually administered either once or twice postoperatively. With regard to the administration of potent opioid agonists, the 3 major concerns included respiratory depression, bradycardia, and sedation in dogs, and excitement, respiratory depression, and bradycardia in cats. Seventy-seven percent of veterinarians considered their knowledge of issues related to the recognition and control of postoperative pain to be inadequate. Experience in practice is currently the major source of knowledge, with undergraduate veterinary school and research articles in journals ranked as the least important sources. Lectures or seminars delivered at the regional level were the preferred format for continuing education.
Postoperative continuous wound infusion of ropivacaine has comparable analgesic effects and fewer complications as compared to traditional patient-controlled analgesia with sufentanil in patients undergoing non-cardiac thoracotomy
Liu, Fang-Fang; Liu, Xiao-Ming; Liu, Xiao-Yu; Tang, Jun; Jin, Li; Li, Wei-Yan; Zhang, Li-Dong
Objective: To compare the postoperative analgesic effects of continuous wound infusion of ropivacaine with traditional patient-controlled analgesia (PCA) with sufentanil after non-cardiac thoracotomy. Methods: One hundred and twenty adult patients undergoing open thoracotomy were recruited into this assessor-blinded, randomized study. Patients were randomly assigned to receive analgesia through a wound catheter placed below the fascia and connected to a 2 ml/h ropivacaine 0.5% (RWI group) or sufentanil PCA (SPCA group). Analgesia continued for 48 h. Visual analogue scores (VAS) at rest and movement, Ramsay scores and adverse effects were recorded at 2, 8, 12, 24, 36 and 48 h after surgery. Three months after discharge, patient’s satisfaction, residual pain and surgical wound complications were assessed. Results: General characteristics of patients were comparable between two groups. There were no statistical differences in the VAS scores and postoperative pethidine consumption between two groups (P > 0.05). However, when compared with SPCA group, the incidences of drowsiness, dizziness and respiratory depression, ICU stay and hospital expenditure reduced significantly in RWI group (P < 0.05). Patients’ satisfaction with pain management was also improved markedly in RWI group (P < 0.05). Conclusion: Continuous wound infusion with ropivacaine is effective for postoperative analgesia and has comparable effects to traditional PCA with sufentanil. Furthermore, this therapy may also reduce the incidences of drowsiness, dizziness, respiratory depression and decrease the ICU stay and hospital expenditure. PMID:26131121
Unlügenç, H; Gündüz, M; Ozalevli, M; Akman, H
We tested whether, after major abdominal surgery, the addition of magnesium or ketamine to tramadol for intravenous (IV) patient-controlled analgesia (PCA) improved analgesia and lowered pain scores, compared to a PCA containing only tramadol. Sixty-six patients were allocated randomly to receive a PCA with tramadol alone (T), tramadol plus magnesium (TM) or tramadol plus ketamin (TK), in a double-blind randomized study. Postoperative analgesia was started when the verbal rating scale (VRS) score was 2 or more. Following a loading dose of the study solution (which contained 1 mg/kg tramadol), a background infusion of 0.4 mg/kg/h was started. Patients were allowed to use bolus doses of 0.2 mg/kg every 20 min without a time limit. Discomfort, sedation, pain scores, total and bolus PCA tramadol consumption, and side-effects, were recorded for up to 24 h after the start of PCA. Pain and discomfort scores were lower (P < 0.01) in groups TM and TK at 15, 30, 60 and 120 min than in group T. The addition of magnesium or ketamine significantly reduced the consumption of tramadol at 6, 12 and 24 h (P < 0.01). The incidence of nausea did not differ between the groups. Adding magnesium or ketamine to tramadol improved analgesia and patient comfort and decreased the amount of tramadol required for postoperative pain management after major abdominal surgery.
Sen, Sumana; Bathini, Prapthi
Managing postoperative pain efficiently is one important therapeutic challenge in the hospitals. Combination use of analgesics is in vogue, where in drugs from the opioid and non-opioid group are given synergistically. The aim of this study is to audit the use of different analgesics on the first postoperative day. Effort has been made to look into the drug or drug combinations used and other factors associated with their use. Retrospective, cross sectional observational study was conducted over a period of 11 months in a tertiary care teaching hospital at Hyderabad with approval from institutional ethics committee. Medical records of 649 patients on the first postoperative day were analysed for analgesics by various indicators. Average number of drugs per encounter was 4.23. Percentage of patients prescribed drugs from national essential drug list/WHO was 81.94%. Most common analgesic (monotherapy) prescribed was tramadol followed by diclofenac and the most common combination drugs prescribed were tramadol+Paracetamol. The most common route of administration was intravenous. All the drugs except piroxicam, were in the lower limit of the recommended daily dose. The present study gives an idea of the overall pattern of analgesic drug use in postoperative patients. The drug combinations used, the most common single use drug can be made out. The health professionals can be encouraged to prescribe by generic name and from the National List of Essential Medicines NLEMs.
Polat, Reyhan; Peker, Kevser; Gülöksüz, Çiğdem Topçu; Ergil, Julide; Akkaya, Taylan
The aim of this study was to compared the efficacy of paracetamol-codeine phosphate and naproxen sodium-codeine phosphate on postoperative pain and tramadol consumption during the first 24 hours after a lumbar disk surgery. After Ethics Committee approval and informed consent had been obtained, 64 patients were allocated into three groups. Patients received oral paracetamol-codeine (300 mg + 30 mg; Group P), naproxen sodium-codeine (550 mg + 30 mg; Group N), or placebo tablets (Group C) 30 minutes prior to induction of anesthesia. Patient-controlled analgesia was supplied postoperatively using tramadol. Pain intensity, tramadol consumption, and side effects were recorded every 1 hour, 2 hours, 6 hours, 12 hours, and 24 hours after surgery. Whole study period pain intensity (visual analogue scale scores) was lower in Group P (p = 0.007) and Group N (p = 0.001), compared with Group C, however, there was no statistically significant difference between Group P and Group N regarding pain intensity (p > 0.05). Tramadol consumption was lower in Group P and Group N, compared with Group C (p < 0.001), and in turn the lowest incidence of tramadol consumption was detected in Group P compared with Group N (p < 0.001) and Group C (p < 0.001). Side effects were similar between the groups. Preemptive administration of paracetamol-codeine and naproxen sodium-codeine combination significantly reduced tramadol consumption and provided more effective analgesia compared with placebo. The paracetamol-codeine combination was superior to naproxen sodium-codeine with regard to tramadol consumption. Copyright © 2015. Published by Elsevier Taiwan.
Teixeira, Renata Cr; Monteiro, Eduardo R; Campagnol, Daniela; Coelho, Karina; Bressan, Thais F; Monteiro, Betânia S
To compare the effects of tramadol alone, or in combination with dipyrone or meloxicam, on postoperative pain and analgesia requirement after unilateral mastectomy with or without ovariohysterectomy in dogs. Prospective, randomized, clinical study. Twenty seven bitches undergoing unilateral mastectomy with or without ovariohysterectomy. Anesthesia was induced with propofol and maintained with isoflurane and a constant rate infusion of morphine. Before the end of surgery, dogs were randomly assigned to receive intravenous tramadol alone (3 mg kg(-1), group T), combined with dipyrone (30 mg kg(-1), group TD) or meloxicam (0.2 mg kg(-1), group TM). Dogs received additional doses of tramadol (groups T and TM) or tramadol with dipyrone (group TD) at 8 and 16 hours after extubation. Postoperative pain was assessed by a blinded observer before anesthesia (baseline) and at 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours after extubation using a visual analog scale (VAS) and a modified Glasgow scale. Rescue analgesia (morphine, 0.5 mg kg(-1)) was administered if the Glasgow pain score was >3.5. There were no significant differences among groups in pain scores evaluated by the VAS or the Glasgow scale. In groups T, TD and TM, pain scores were significantly higher than at baseline for 6, 8 and 2 hours, respectively. Rescue analgesia was administered to 3/9, 2/9 and 1/9 dogs in groups T, TD and TM, respectively (p > 0.05) [Correction added on 15 August 2013, after first online publication: 'T, TM and TD' was changed to 'T, TD and TM'.]. Under the conditions of this study, tramadol alone or in combination with dypyrone or meloxicam provided effective analgesia for 24 hours in most dogs after unilateral mastectomy with or without ovariohysterectomy. Further evaluation of combination therapies is needed in larger groups of dogs. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.
Kadam, Vasanth Rao
The quadratus lumborum (QL) block as a postoperative analgesic method following abdominal surgery has been described by Blanco for superficial surgeries but not used for major laparotomy. This ipsilateral QL block had low pain scores and opioid use on day one with sensory block upto T8-L1. The options of various volume used and pros and cons are discussed.
Rosenquist, J.B.; Nystrom, E.
In a double-blind crossover study, the effect on postoperative pain of lidocaine plus diflunisal was compared with that of bupivacaine and placebo. Forty-eight patients with bilateral impactions of lower third molars had these removed on two occasions four weeks apart. One pain-control regimen was used on one occasion and the alternate on the second. The pain intensity was indicated on a visual analog scale at 2, 3, 4, 5, and 6 hours postoperatively. The pain values for the first postoperative hours were higher for the lidocaine diflunisal combination, whereas after 5 hours the opposite was true. Significantly more patients preferred the combination of lidocaine and diflunisal. Three patients reported fatigue postoperatively during the day of surgery, which they attributed to the operation and not to the analgesics used. PMID:3472476
Balmer, T V; Irvine, D; Jones, R S; Roberts, M J; Slingsby, L; Taylor, P M; Waterman, A E; Waters, C
The postoperative analgesia and sedation in cats given carprofen (4.0 mg/kg bodyweight by subcutaneous injection preoperatively) was compared to that in cats given pethidine (3.3 mg/kg bodyweight by intramuscular injection postoperatively) in a controlled, randomised, blinded, multicentre clinical trial. Further dosing with the particular analgesic was allowed if a cat was exhibiting unacceptable pain. In total, 57 carprofen cases and 59 pethidine cases were evaluated. Significantly fewer cats in the carprofen group required additional doses of analgesic, and mean pain scores were significantly lower from four hours after ovariohysterectomy, and at 18 to 24 hours after castration, compared to the pethidine group. In conclusion, carprofen provided as good a level of postoperative analgesia as pethidine, but of a longer duration (at least 24 hours) and was well tolerated. It thus provides an option for 'pre-emptive analgesia' in cats about to undergo surgery.
Wick, Elizabeth C; Grant, Michael C; Wu, Christopher L
Amid the current opioid epidemic in the United States, the enhanced recovery after surgery pathway (ERAS) has emerged as one of the best strategies to improve the value and quality of surgical care and has been increasingly adopted for a broad range of complex surgical procedures. The goal of this article was to outline important components of opioid-sparing analgesic regimens. Regional analgesia, acetaminophen, nonsteroidal anti-inflammatory agents, gabapentinoids, tramadol, lidocaine, and/or the N-methyl-d-aspartate class of glutamate receptor antagonists have been shown to be effective adjuncts to narcotic analgesia. Nonsteroidal anti-inflammatory agents are not associated with an increase in postoperative bleeding. A meta-analysis of 27 randomized clinical trials found no difference in postoperative bleeding between the groups taking ketorolac tromethamine (33 of 1304 patients [2.5%]) and the control groups (21 of 1010 [2.1%]) (odds ratio [OR], 1.1; 95% CI, 0.61-2.06; P = .72). After adoption of the multimodal analgesia approach for a colorectal ERAS pathway, most patients used less opioids while in the hospital and many did not need opioids after hospital discharge, although approximately 50% of patients received some opioid during their stay. Multimodal analgesia is readily available and the evidence is strong to support its efficacy. Surgeons should use this effective approach for patients both using and not using the ERAS pathway to reduce opioid consumption.
Au, Alvin Ho Yeung; Choi, Siu Wai; Cheung, Chi Wai; Leung, Yiu Yan
Objectives To run a systematic review and meta-analysis of randomized clinical trials aiming to answer the clinical question “which analgesic combination and dosage is potentially the most effective and safe for acute post-operative pain control after third molar surgery?”. Materials and Methods A systematic search of computer databases and journals was performed. The search and the evaluations of articles were performed by 2 independent reviewers in 3 rounds. Randomized clinical trials related to analgesic combinations for acute post-operative pain control after lower third molar surgery that matched the selection criteria were evaluated to enter in the final review. Results Fourteen studies with 3521 subjects, with 10 groups (17 dosages) of analgesic combinations were included in the final review. The analgesic efficacy were presented by the objective pain measurements including sum of pain intensity at 6 hours (SPID6) and total pain relief at 6 hours (TOTPAR6). The SPID6 scores and TOTPAR6 scores of the reported analgesic combinations were ranged from 1.46 to 6.44 and 3.24 – 10.3, respectively. Ibuprofen 400mg with oxycodone HCL 5mg had superior efficacy (SPID6: 6.44, TOTPAR6: 9.31). Nausea was the most common adverse effect, with prevalence ranging from 0-55%. Ibuprofen 200mg with caffeine 100mg or 200mg had a reasonable analgesic effect with fewer side effects. Conclusion This systematic review and meta-analysis may help clinicians in their choices of prescribing an analgesic combination for acute post-operative pain control after lower third molar surgery. It was found in this systematic review Ibuprofen 400mg combined with oxycodone HCL 5mg has superior analgesic efficacy when compared to the other analgesic combinations included in this study. PMID:26053953
Verron, Elise; Gauthier, Olivier; Janvier, Pascal; Le Guen, Herve; Holopherne, Delphine; Cavagna, Remi; Bouler, Jean-Michel
Synthetic calcium-deficient apatites (CDA) are structurally similar to biological apatites and are well known as chemical precursors of biphasic calcium phosphates (BCP). BCP are mixtures of hydroxyapatite and beta-tricalcium phosphate and are widely used as bone substitutes in human surgery. Bupivacaine, a local anesthetic, has been loaded onto CDA using isostatic compaction. The purpose of this study was to evaluate the in vivo performance of such a local release on pain after having previously defined the in vitro release profile of bupivacaine. CDA was loaded with 1%, 4%, and 16% of bupivacaine using an isostatic compaction process. In vitro release profile assays performed indicated the complete release of bupivacaine after 24 h. Wistar male rats received 50 mg implants of CDA associated, respectively, with 0, 1%, 4%, and 16% of bupivacaine into the distal femur. Analgesia was measured using the electronic version of the Von Frey monofilament test, assessing the inflammatory response and a neurological score. During the first postoperative days, a dose-dependent analgesic effect was observed with the bupivacaine adsorbed on the resorbable implant. This combined device system thus appears to release local anesthetic in a manner that prevents or limits postoperative pain following bone surgery. This innovative approach could be integrated into a global pain management program, for example, in the context of bone harvesting where bone reconstruction is required.
Eroğlu, Mehmet; Er, Mehmet Serhan; Altınel, Levent; Kokulu, Serdar; Yücehan, Mehmet
This study aims to evaluate the analgesic and functional efficacy of subcutaneous local analgesic infusion (ScLAI) in the early postoperative period (especially on the second postoperative day) in patients undergoing simultaneous bilateral total knee arthroplasty with an intraoperative periarticular injection (PAI) of local analgesic cocktail. Fifteen patients (1 male, 14 females; mean age 62 years; range 52 to 76 years) who underwent simultaneous bilateral total knee arthroplasty (30 knees) and who received the same pre- and intraoperative analgesic protocols were included in this randomized, double-blind, placebo-controlled study. By using a flexible catheter, bupivacaine was administered for ScLAI to either knee (ScLAI group) and placebo infusion was applied to the other one (control group). Postoperative visual analog scale (VAS) pain scores and knee functions were compared between bupivacain and placebo infused knees. In the ScLAI group, VAS pain scores were lower than the control group during knee flexion and straight leg raise activities (SLR) on the second postoperative day. ScLAI also prevented the rebound pain following intraoperative PAI of local analgesic cocktail and prolonged the analgesic efficacy period of the cocktail during both knee flexion and SLR. Subcutaneous infusion of bupivacaine in patients undergoing simultaneous bilateral total knee arthroplasty may prevent emergence of the rebound pain arising after application of intraoperative PAI of local analgesic cocktail and prolong the analgesic efficacy of the cocktail during both knee flexion and SLR activities on the second postoperative day.
Fuzier, Régis; Serres, Isabelle; Bourrel, Robert; Palmaro, Aurore; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse
Knee arthroplasty remains the gold standard in the treatment of severe osteoarthritis. Chronic postoperative pain has been reported with a prevalence ranging from 15% to 47%. The aim of this study was to compare analgesic drug consumption before and after surgery as an indicator of pain after knee surgery. A pharmacoepidemiological method comparing analgesics and antineuropathic issues 1 year before and 1 year after surgery was used. All patients who underwent knee arthroplasty in the Midi-Pyrenees region (2.5 million inhabitants) were identified through the Health Insurance System Database. Increase of drug issues (all analgesics, antineuropathic drugs, strong opioids) was calculated and compared between several periods surrounding the surgery (12 months, 2 months, and 10 months before and after the knee arthroplasty). A multivariate logistic regression model was used to identify factors associated with chronic postoperative pain. The study included 1939 patients. An increase in analgesic, antineuropathic, and opioid drug consumption was observed the year after the surgery in 47.3%, 8.6%, and 5.6% of patients, respectively. Multivariate analysis found a significant association between type of surgery (total knee vs unicompartmental arthroplasty) and analgesic consumption 1 year after surgery, and between preoperative pain and psychiatric vulnerability and increase in neuropathic drug dispensing. Conversely, older age was considered as a protective factor. This study revealed that an increase in the issue of different analgesic drugs is present in half of patients 1 year after knee arthroplasty. Several associated factors of drug consumption (preoperative pain, type of surgery, and psychiatric disorder) were identified.
Moore, R Andrew; Derry, Sheena; Aldington, Dominic; Wiffen, Philip J
This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events are now dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews and assesses the reliability of available data. To summarise the efficacy of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery who have been given a single dose of oral analgesic. We identified systematic reviews in the Cochrane Database of Systematic Reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome the number of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews, we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, and the percentage of participants remedicating by six, eight, 12, or 24 hours. Where there was adequate information for pairs of drug and dose (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable. The overview included 39 separate Cochrane Reviews with 41 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 50,000 participants in approximately 460 individual studies. The individual reviews included only high-quality trials of standardised design
Andersen, Lars Peter Holst
standard statistical test. Furthermore, we presented an integrated assessment method of longitudinally measured pain intensity and opioid consumption. Our analyses documented that the employed statistical method impacted the statistical significance of post-operative analgesic outcomes. Furthermore, the novel integrated assessment method combines two interdependent outcomes, lowers the risk of type 2 errors, increases the statistical power, and provides a more accurate description of post-operative analgesic efficacy. Exogenous melatonin may offer an effective and safe analgesic drug. At this moment, however, the results of human studies have been contradictory. High-quality randomized experimental- and clinical studies are still needed to establish a "genuine" analgesic effect of the drug in humans. Other perioperative effects of exogenous melatonin should also be investigated, before melatonin can be introduced for clinical routine use in surgical patients. Despite promising experimental and clinical findings, several unanswered questions also relate to optimal dosage, timing of administration and administration route of exogenous melatonin.
Montero Matamala, A; Bertolotti, M; Contini, M P; Guerrero Bayón, C; Nizzardo, A; Paredes Lario, I; Pizà Vallespir, B; Scartoni, S; Tonini, G; Capriati, A; Pellacani, A
Multimodal analgesia constitutes a common strategy in pain management. A tramadol hydrochloride 75 mg/dexketoprofen 25 mg oral fixed combination (TRAM/DKP 75 mg/25 mg) has been recently registered and released in Europe for the treatment of moderate-to-severe acute pain. This paper provides additional analyses on the results of two phase III clinical trials (DEX-TRA-04 and DEX-TRA-05) on postoperative pain to document its sustained effect. The analysis was applied to a modified intention-to-treat population (mITT, n = 933) of patients undergoing active treatment from the first dose, to assess the sustained effect of TRAM/DKP 75 mg/25 mg on pain intensity (PI-VAS 0-100) over 56 h from first drug intake. The superior analgesic effect of TRAM/DKP 75 mg/25 mg over 56 h in terms of difference in PI-VAS (mean [SE]) was shown for DEX-TRA-04 (-11.0 [0.55] over dexketoprofen 25 mg and -9.1 [0.55] over tramadol 100 mg, P ≤ 0.0001) and for DEX-TRA-05 (-10.4 [0.51] over dexketoprofen 25 mg and -8.3 [0.51] over tramadol 100 mg, P ≤ 0.0001). The statistical analysis performed on data coming from both studies confirms the superior sustained analgesia of TRAM/DKP 75 mg/25 mg over tramadol 100 mg and dexketoprofen 25 mg. These results are consistent with the previously published data obtained on the ITT population and strongly support the role of this oral fixed-dose combination in the treatment of moderate-to-severe acute pain. Copyright 2017 Clarivate Analytics.
Murphy, Jamie D; Gelfand, Harold J; Bicket, Mark C; Ouanes, Jean-Pierre P; Kumar, Kanupriya K; Isaac, Gillian R; Wu, Christopher L
Pruritus may be a significant problem for patients in the postoperative period. There are many options for the treatment of pruritus including intravenous (IV) naloxone. However, it is not clear whether the use of IV naloxone may also affect analgesia or other opioid-related side effects. The authors have performed a systematic review to further examine this issue. Systematic literature searches of the National Library of Medicine's PubMed and EMBASE databases were conducted using terms related to postoperative use of IV naloxone. Only randomized controlled trials comparing IV naloxone used either as a continuous infusion or part of an IV patient-controlled analgesia (PCA) regimen after surgical procedures were considered. The data on pertinent study characteristics and relevant outcomes were extracted from accepted articles. There was no restriction on language for inclusion. Meta-analysis was performed using the Review Manager 4.2.10 (The Cochrane Collaboration, 2004). A random effects model was used. The literature searches yielded eight articles that met all inclusion criteria. There were a total of 424 subjects in the naloxone group and 376 in the saline group. The authors found that the use of naloxone was associated with a decreased risk for pruritus (odds ratio [OR] = 0.40, 95% confidence interval [CI] = 0.21-0.79, p = 0.006] and nausea [OR = 0.62, 95% CI = 0.43-0.89, p = 0.009]. However, the use of IV naloxone (vs no naloxone) did not significantly influence the risk of postoperative emesis [OR = 0.97, 95% CI = 0.70-1.33, p = 0.83], opioid consumption [OR = 0.29, 95% CI = -3.54-4.13, p = 0.88], or sedation [OR = 0.82, 95% CI = 0.38-1.74, p = 0.60]. Finally, the use of IV naloxone did not appear to be associated with any significant change in visual analog score pain scores at 24 hours postoperatively (weighted mean difference = -0.14, 95% CI = -0.50-0.23, p = 0.46). Our pooled analysis examining the analgesic efficacy of IV naloxone (either as a continuous
Singh, Anil P.; Singh, Dharmraj; Singh, Yashpal; Jain, Gaurav
Background: Postoperative pain control after major abdominal surgery is the prime concern of anesthesiologist. Among various methodologies, epidural analgesia is the most preferred technique because of the excellent quality of analgesia with minimum side-effects. Aim: The present study was designated to compare postoperative analgesic efficacy and safety of epidural tramadol as adjuvant to ropivacaine (0.2%) in adult upper abdominal surgery. Settings and Design: Prospective, randomized-controlled, double-blinded trial. Materials and Methods: Ninety patients planned for upper abdominal surgery under general anesthesia were randomized into three equal groups to receive epidural drug via epidural catheter at start of incisional wound closure: Group R to receive ropivacaine (0.2%); Group RT1 to receive tramadol 1 mg/kg with ropivacaine (0.2%); and RT2 to receive tramadol 2 mg/kg with ropivacaine (0.2%). Duration and quality of analgesia (visual analog scale [VAS] score), hemodynamic parameters, and adverse event were recorded and statistically analyzed. Statistical Analysis: One-way analysis of variance test, Fisher's exact test/Chi-square test, whichever appropriate. A P < 0.05 was considered significant. Results: Mean duration of analgesia after epidural bolus drug was significantly higher in Group RT2 (584 ± 58 min) when compared with RT1 (394 ± 46 min) or R Group (283 ± 35 min). VAS score was always lower in RT2 Group in comparison to other group during the study. Hemodynamic parameter remained stable in all three groups. Conclusion: We conclude that tramadol 2 mg/kg with ropivacaine (0.2%) provides more effective and longer-duration analgesia than tramadol 1 mg/kg with ropivacaine (0.2%). PMID:26712976
Pétrault, Maud; Gautier, Sophie; Bérézowski, Vincent; Ouk, Thavarak; Bastide, Michèle; Pétrault, Olivier; Bordet, Régis
Analgesics such as opioid agonists are usually not given during the postoperative phase of experimental stroke because they are susceptible to interfere with the evaluation of neuroprotective therapies. Here, we investigate the potential of acetaminophen and nefopam, two nonopioid analgesic drugs, to exert an analgesic effect without inducing neuroprotection in a murine model of ischemic stroke. We demonstrate that acetaminophen (200 mg/kg, PO) induces a significant decrease in the infarct volume, particularly in the cortex (VEHICLE: 200.1 mm(3) vs. 140.9 mm(3) , P < 0.05), while nefopam (2, 20 or 40 mg/kg, IM), administered at the end of middle cerebral artery occlusion (MCAO), do not influence the infarct size (VEHICLE: 268.6 mm(3) vs. NEFOPAM 2: 248.8 mm(3) , NEFOPAM 20: 250.6 mm(3) and NEFOPAM 40: 215.9 mm(3) , P > 0.05). Moreover, we find that nefopam administration (20 mg/kg, IM) in the acute postoperative phase do not change the level of neuroprotection induced by MK801 (3 mg/kg, IV), a well-known neuroprotectant (VEHICLE: 268.6 mm(3) vs. MK801: 194.4 mm(3) and vs. MK801 + NEFOPAM 20: 195.2 mm(3) ). On the other hand, although nefopam induces analgesia in healthy animals, it is not the case when administered during MCAO (behavior scores at 5 min: HEALTHY: 2.1 vs. HEALTHY + NEFOPAM 20: 0.6, P < 0.5; IR: 0.40 vs. IR + NEFOPAM 20: 0.67, P > 0.05). Our data suggest that neither acetaminophen nor nefopam can be used as analgesic agents to meet the needs of limiting rodent pain and distress during experimental stroke surgery. © 2016 Société Française de Pharmacologie et de Thérapeutique.
Wu, C L; Bronstein, R D; Chen, J M; Lee, D H; Rouse, L M
Anterior cruciate ligament (ACL) procedures are associated with significant postoperative pain and have traditionally been done on a short-stay hospitalization basis because of concerns for adequate postoperative analgesia. A retrospective chart review was performed to determine postoperative intravenous patient-controlled analgesia (PCA) morphine requirements for 80 patients who had undergone arthroscopically assisted ACL reconstruction under general anesthesia by means of a patellar tendon autograft by 1 of 2 surgeons. The mean +/- SD PCA morphine used after surgery was 20.4+/-20.0 mg. There was a wide interpatient difference in postoperative opioid consumption: the amount of PCA morphine used ranged from 0 mg to 124 mg. A comparison between the surgeons revealed that 1 surgeon had significantly longer intraoperative surgical, tourniquet, and anesthesia times; however, there was no difference in the length of recovery room stay, amount of postoperative PCA morphine used, or time to hospital discharge. Predicting which patients may benefit from short-stay hospitalization after arthroscopic ACL reconstruction may be difficult because of considerable interpatient differences in postoperative analgesic requirements.
Fanelli, Andrea; Ruggeri, Matteo; Basile, Michele; Cicchetti, Americo; Coluzzi, Flaminia; Della Rocca, Giorgio; Di Marco, Pierangelo; Esposito, Clelia; Fanelli, Guido; Grossi, Paolo; Leykin, Yigal; Lorini, Ferdinando Luca; Paolicchi, Adriana; Scardino, Marco; Corcione, Antonio
The aim of this analysis is to evaluate the costs of 72-hour postoperative pain treatment in patients undergoing major abdominal, orthopedic and thoracic procedures in nine different Italian hospitals, defined as the cumulative cost of drugs, consumable materials and time required for anesthesiologists, surgeons and nurses to administer each analgesic technique. Nine Italian hospitals have been involved in this study through the administration of a questionnaire aimed to acquire information about the Italian clinical practice in terms of analgesia. This study uses activity-based costing (ABC) analysis to identify, measure and give value to the resources required to provide the therapeutic treatment used in Italy to manage the postoperative pain patients face after surgery. A deterministic sensitivity analysis (DSA) has been performed to identify the cost determinants mainly affecting the final cost of each treatment analyzed. Costs have been reclassified according to three surgical macro-areas (abdominal, orthopedic and thoracic) with the aim to recognize the cost associated not only to the analgesic technique adopted but also to the type of surgery the patient faced before undergoing the analgesic pathway. Fifteen different analgesic techniques have been identified for the treatment of moderate to severe pain in patients who underwent a major abdominal, orthopedic or thoracic surgery. The cheapest treatment actually employed is the oral administration "around the clock" (€ 8.23), whilst the most expensive is continuous peripheral nerve block (€ 223.46). The intravenous patient-controlled analgesia costs € 277.63. In terms of resources absorbed, the non-continuous administration via bolus is the gold standard in terms of cost-related to the drugs used (€ 1.28), and when administered pro re nata it also absorbs the lowest amount of consumables (€0.58€) compared to all other therapies requiring a delivery device. The oral analgesic administration pro re
Chen, L-C; Elliott, R A; Ashcroft, D M
To evaluate the relative analgesic efficacy and tolerability of single-dose COX-2 inhibitors in post-operative pain management. Systematic review of randomized controlled trials (RCTs). The area under the pain relief vs. time curve was used to evaluate the proportion of patient achieving at least 50% pain relief using validated equations. The proportions of patients experiencing any adverse event or specific adverse events were also examined. In all, 18 RCTs were included which contained 2783 patients. The results of the effects of single-dose analgesics on the basis of 50% of patients achieving pain relief over 6 h from dental pain models suggested that oral rofecoxib 50 mg was more effective than codeine/paracetamol 60/600 mg, and the rate ratio (RR) was 2.11 (95% CI 1.6-2.75). Valdecoxib 40 mg was also more effective than oxycodone/paracetamol 10/1000 mg (RR 1.34; 95% CI 1.11-1.62). There was no significant differences between other oral COX-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs), except that celecoxib 200 mg was less effective than ibuprofen 400 mg (RR 0.66; 95% CI 0.48-0.90) and rofecoxib 50 mg (RR 0.65; 95% CI 0.49-0.87). The results from orthopaedic pain model showed no significant difference between rofecoxib 50 mg and naproxen sodium 550 mg (RR 1.04; 95% CI 0.73-1.49). The adverse effects of single-dose COX-2 inhibitor used in short-term post-operative pain management were generally mild and less than non-selective NSAIDs, although there was no significant difference. The analgesic efficacy and tolerability of single-dose COX-2 inhibitors were more effective than opioid-containing analgesics and similar to non-selective NSAIDs in post-operative pain management. Further studies are needed to examine the efficacy and tolerability of COX-2 inhibitors compared against active comparators over a longer duration to assess whether these short-term effects are mirrored by longer-term outcomes and to determine their ultimate
Wong, Yin J
Data sourcesThe Cochrane Database of Systematic Reviews on the Cochrane Library.Study selectionAll Cochrane reviews of RCTs between 1999 to 2015, conducted in adults examining the adverse events associated with single dose oral analgesics used for acute post-operative pain were considered.Data extraction and synthesisStudies were searched, reviewed and assessed independently by two reviewers and standard data items extracted. Methodological quality was assessed using criteria adapted from AMSTAR (Assessing the Methodological Quality of Systematic Reviews).ResultsData from 39 Cochrane reviews of 41 different analgesics or analgesic combinations involving a total of 350 studies involving 35,000 adults were included. Most analgesics were tested in a narrow dose range. For most NSAIDs, paracetamol (acetaminophen), and combinations not containing opioids, the rates of adverse events were similar to that of placebos (NSAID 3% - 44% vs 4 - 46%; paracetamol 7-18% vs 6-16%; combination 11-30% vs 6-48%). However, for higher dosages, like 1000 mg aspirin, 1000 mg diflunisal, and opioids or drug combinations containing opioids, there was a statistically significant difference in the incidence of adverse events reported (NNH 7.7(95%CI; 4.8 - 20) for 1000 mg aspirin; 7.5(95%CI; 4.8-17) for 1000 mg diflunisal; 3.5-8.6 for opioids and combinations). Serious adverse events were rare, occurring at about 1 in 3,200.ConclusionsDespite ongoing problems with the measurement, recording and reporting of adverse events in clinical trials and in systematic reviews, the large amount of information available for single oral doses of analgesics provides evidence that adverse events rates are generally similar with active drug and placebo in these circumstances, except at higher doses of some drugs, and in combinations including opioids.
Kormi, Eeva; Snäll, Johanna; Koivusalo, Anna-Maria; Suominen, Anna Liisa; Thorén, Hanna; Törnwall, Jyrki
To clarify the effect of systemic dexamethasone (DXM) on pain and postoperative opioid (oxycodone) consumption after blowout fracture surgery. A prospective randomized observer-blinded trial of 20 patients who had a blowout fracture requiring surgical intervention was conducted. Patients were randomly assigned to receive a total dose of intravenous DXM 30 mg perioperatively or no DXM (controls). Pain was assessed postoperatively using a 10-cm visual analog scale (VAS) each time analgesics (acetaminophen every 6 hours or oxycodone upon request) were administered. The VAS area under the curve (VAS AUC) for 24 hours postoperatively represented the outcome. Data were analyzed using χ(2) test, Student t test, 2-tailed Mann-Whitney U test, and linear regression, with a P value less than .05 indicating significance. Patients with blowout fracture receiving perioperative systemic DXM exhibited a significantly lower average VAS AUC (P = .04). After controlling for other confounding variables, this result remained significant (P = .03). DXM appears to decrease postoperative pain and thus is recommended as a pre-emptive analgesic in blowout fracture surgery. Copyright © 2017. Published by Elsevier Inc.
Hobson, Anna; Wiffen, Philip J; Conlon, Joy A
Acute postoperative pain occurs as a result of tissue damage following surgery. Administering the appropriate analgesia to children is a complex process and it is unclear whether children's postoperative pain is more successfully treated by using 'as required' (when pain occurs) (termed 'pro re nata' or PRN) or (irrespective of pain at the time of administration). To assess the efficacy of as required versus fixed schedule analgesic administration for the management of postoperative pain in children under the age of 16 years. On 2 July 2014, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and CINAHL databases. We reviewed the bibliographies of all included studies and of reviews, and searched two clinical trial databases, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, to identify additional published or unpublished data. We included randomised controlled trials (RCTs) comparing PRN versus ATC analgesic administration for postoperative pain in children under the age of 16 years who had undergone any surgical procedure requiring postoperative pain relief, in any setting. Two review authors (AH, PW) independently extracted efficacy and adverse event data, examined issues of study quality, and assessed risk of bias as recommended in the Cochrane Handbook for Systematic Reviews of Interventions. We included three RCTs (four reports) of 246 children aged under 16 years undergoing tonsillectomy. Children were given weight-appropriate doses of the study medication, either PRN or ATC, by a parent or carer at home for up to four days following surgery. We did not identify any studies assessing the management of postoperative pain in children in any other setting (i.e. as an inpatient). All studies included in this review were based on the use of paracetamol, and an opioid was added to paracetamol in two studies. Analgesics were administered either orally (tablet or elixir
Anıl, Ali; Kaya, Fatma Nur; Yavaşcaoğlu, Belgin; Mercanoğlu Efe, Esra; Türker, Gürkan; Demirci, Abdurrahman
The aim of this study is to compare the effects of intravenous single-dose dexketoprofen trometamol and diclofenac sodium 30 minutes before the end of the surgery on relief of postoperative pain in patients undergoing laparoscopic cholecystectomy. A randomized fashion. Sixty (American Society of Anesthesiologist class I-II) patients undergoing laparoscopic cholecystectomy were divided into 2 groups Patients in group DT received 50 mg dexketoprofen trometamol, whereas patients in group DS received 75 mg diclofenac sodium, intravenously 30 minutes before the end of surgery. Postoperative pain intensity, morphine consumption with patient-controlled analgesia, time to first analgesic requirement, complications, rescue analgesic (intravenous tenoxicam 20 mg) requirement, and duration of hospital stay were recorded. Postoperative pain visual analog scale scores were similar in the follow-up periods (P > .05). Patient-controlled analgesia morphine consumption was significantly less in group DT compared with group DS in all postoperative follow-up periods (2 and 4 hours: P < .01; 8, 12, 18, and 24 hours: P < .001). In the postoperative period, the first analgesic requirement time was significantly longer in group DT compared with group DS (P < .01). In addition, the number of patients requiring rescue analgesic was higher in group DS compared with group DT (P < .01). Other follow-up parameters were similar. In our study, administration of intravenous single-dose dexketoprofen trometamol 30 minutes before the end of surgery provided effective analgesia with reduced consumption of opioids and requirement for rescue analgesic compared with diclofenac sodium in patients undergoing laparoscopic cholecystectomy. For this reason, we believe that, as a part of multimodal analgesia, dexketoprofen trometamol provides more effective analgesia than diclofenac sodium in patients undergoing laparoscopic cholecystectomy. Copyright © 2016 Elsevier Inc. All rights reserved.
Karaman, Semra; Kocabaş, Seden; Zincircioğlu, Ciler; Firat, Vicdan
The aim of this study was to determine if preemptive use of the NMDA receptor antogonist ketamine decreases postoperative pain in patients undergoing abdominal hystrectomy. A total of 60 patients admitted for total abdominal hysterectomy were included in this study after the approval of the ethic committee, and the patients were randomly classified into three groups. After standart general anaesthesia, before or after incision patients received bolus saline or ketamine. Group S received only saline while Group Kpre received ketamine 0.4 mg/kg before incision and saline after incision, and Group Kpost received saline before incision and 0.4 mg/kg ketamine after incision. Postoperatif analgesia was maintained with i.v. PCA morphine. Pain scores were assessed with Vizüal Analog Scale (VAS), Verbal Rating Scale (VRS) at 1., 2, 3., 4., 8., 12. ve 24. hours postoperatively. First analgesic requirement time, morphine consumption and side effects were recorded. There were no significant differences between groups with respect to VAS / VRS scores, the time for first analgesic dose, and morphine consumption ( p>0.05). Patients in Group S had significantly lower sedation scores than either of the ketamine treated groups ( p<0.05). In conclusion, a single dose of ketamin had no preemptive analgesic effect in patients undergoing abdominal hysterectomy, but further investigation is needed for different operation types and dose regimens.
Lascelles, B D; Cripps, P; Mirchandani, S; Waterman, A E
The aim of this study was to titrate the optimal dose of carprofen for single dose usage, for alleviating postoperative pain, under a double-blind and randomised protocol, using both negative and positive controls. Renal tolerance was assessed by screening plasma urea and creatinine. Pre- and postoperative assessment of pain and sedation was made using a dynamic and interactive visual analogue scoring system in 60 cats undergoing ovariohysterectomy. The cats were randomly assigned to one of six groups: (1) carprofen at 1.0 mg/kg subcutaneously (sc); (2) carprofen at 2.0 mg/kg sc; (3) carprofen at 4.0 mg/kg sc; (4) pethidine at 5.0 mg/kg intramuscularly (im), (5) pethidine at 10.0 mg/kg im: and (6) no analgesics (injection of saline). All injections were given postoperatively on tracheal extubation and administered in a double-blind manner. Assessments were made up to 20 hours post extubation. Prior to induction and at 20 hours post extubation, blood samples were taken for laboratory analysis of the urea and creatinine content to check for any adverse effect on renal function. Cats given pethidine did not appear more sedated than the groups receiving carprofen or saline. Cats receiving carprofen were in less pain postoperatively overall, with 4.0 mg/kg being the most effective dose rate (significantly better than the other doses of carprofen at four and eight hours post extubation). The highest dose of pethidine provided significantly better analgesia than the highest dose of carprofen up to two hours post extubation, but from two to 20 hours post extubation carprofen at 4.0 mg/kg provided significantly better analgesia than the pethidine. None of the analgesic regimens appeared to affect renal function adversely, as measured by urea and creatinine levels.
Guler, Gulen; Karaoglu, Sinan; Velibasoglu, Hediye; Ramazanogullari, Nesrin; Boyaci, Adem
This study compared the analgesic effect of intra-articular injection of tenoxicam with that of morphine on postoperative pain after anterior cruciate ligament (ACL) reconstruction. Forty-two patients undergoing arthroscopically ACL reconstructions using hamstring tendons underwent the same anesthetic protocol. The patients were randomized to receive 25 ml normal saline, 20 mg tenoxicam in 25 ml normal saline, or 2 mg morphine in 25 ml normal saline. Postoperative pain was assessed using a visual analogue scale and measuring analgesic requirements. We found both that both intra-articular tenoxicam and intra-articular morphine provided better analgesia than that in the control group. Although pain scores were similar between tenoxicam and morphine groups 30 min postoperative, the analgesic requirements in with tenoxicam were significantly lower than those with morphine group 3-6 h postoperatively.
Al-Gizawiy, Mona M; P Rudé, Elaine
To compare carprofen to butorphanol, with regard to postsurgical analgesic effects, duration of analgesia, and adverse side effects. Blinded, randomized clinical study. Seventy-one cats, 0.5-5 years of age, weighing 3.24 +/- 0.61 kg, undergoing ovariohysterectomy (OHE). Cats were premedicated with subcutaneous atropine (0.04 mg kg(-1)), acepromazine (0.02 mg kg(-1)), and ketamine (5 mg kg(-1)). Anesthesia was induced with ketamine (5 mg kg(-1)) and diazepam (0.25 mg kg(-1)) given intravenously, and maintained with isoflurane. There were three treatment groups: group C (4 mg kg(-1) carprofen SC at induction), group B (0.4 mg kg(-1) butorphanol SC at end of surgery), and group S (0.08 mL kg(-1) of sterile saline SC at induction and end of surgery). Behavioral data were collected using a composite pain scale (CPS), prior to surgery (baseline) and 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours post-surgery. Interaction scores were analyzed separately. Cats with CPS scores >12 received rescue analgesia (meperidine, 4 mg kg(-1), intramuscular). Sixty cats completed the study. The CPS scores did not differ significantly between groups C and B at any time period. CPS scores for groups B and C were significantly increased for 12 hours post-surgery, and in group S for 20 hours. Both group C and B CPS scores were significantly lower than group S in this 20-hour postoperative period, except at 4 hours (B and C) and at 3 and 8 hours (B alone). Interaction scores for group C returned to preoperative baseline 4 hours after surgery, while both groups B and S remained increased for at least 24 hours post-surgery. Nine cats required meperidine. In this study, carprofen provided better postsurgical analgesia than butorphanol. Clinical relevance Neither drug completely abolished pain, however preoperative carprofen provided better pain control compared with postoperative butorphanol in the 24-hour period following OHE surgery in cats.
Ren, Zhen-Yu; Xu, Xiao-Qing; Bao, Yan-Ping; He, Jie; Shi, Le; Deng, Jia-Hui; Gao, Xue-Jiao; Tang, Hui-Lin; Wang, Yu-Mei; Lu, Lin
Individual response to opioid analgesics varies among patients. This study sought to clarify the impact of distinct genetic variations on pain, opioid consumption, and opioid side effects in patients with postoperative pain. A systematic review and meta-analysis of associations between genetic single-nucleotide polymorphisms (SNPs) and opioids used for acute postoperative pain. This meta-analysis examined all studies involving an association between genetic polymorphisms and the analgesic efficacy or clinical outcome of opioid analgesics for postoperative pain. A literature search was performed up to January 31, 2014, using the PubMed, EMBase, ISI Web of Science, and Cochrane Library databases. Fifty-nine studies were included in this systematic review, and 23 studies (a total of 5,902 patients) were included in the final meta-analysis. The results showed that human μ-opioid receptor gene (OPRM1) 118G allele variant carriers consumed more opioids for analgesia (SMD = -0.17, 95% CI = [-0.25, -0.10], P < 0.00001), but reported higher pain scores (MD = -0.11, 95% CI = [-0.17, -0.04], P = 0.002) and less nausea and vomiting (odds ratio = 1.30, 95% CI = [1.08, 1.55], P = 0.005) than the homozygous 118AA patients during the first 24 hour but not the 48 hour postoperative period. Moreover, CYP3A4*1G carriers consumed less opioids than homozygous CYP3A4*1/*1 patients during the first 24 hours postoperative period (MD = 45.12, 95% CI = [36.17, 54.06], P < 0.00001). No significant differences were found in CYP3A5*3, ABCB1 C3435T, and G2477T/A genetic polymorphisms. Some potential non-genetic factors can modify the effects of gene SNP on pain and opioid consumption during the postoperative period, such as age, gender, mood, anxiety, and drug-drug interactions. But further analyses could not be performed in the present meta-analysis due to limited information. The results indicate that among the genetic SNPs we studied which include those affecting analgesic drug metabolism
Liang, De-Yong; Shi, Xiao-You; Sun, Yuan; Clark, J David
Background Opioids have become the mainstay for treatment of moderate to severe pain and are commonly used to treat surgical pain. While opioid administration has been shown to cause opioid-induced hyperalgesia and tolerance, interactions between opioid administration and surgery with respect to these problematic adaptations have scarcely been addressed. Accumulating evidence suggests opioids and nociceptive signaling may converge on epigenetic mechanisms in spinal cord to enhance or prolong neuroplastic changes. Epigenetic regulation of Bdnf (brain-derived neurotrophic factor) and Pdyn (prodynorphin) genes may be involved. Results Four days of ascending doses of morphine treatment caused opioid-induced hyperalgesia and reduced opioid analgesic efficacy in mice. Both opioid-induced hyperalgesia and the reduced opioid analgesic efficacy were enhanced in mice that received hindpaw incisions. The expression of Bdnf and Pdyn (qPCR) was increased after morphine treatment and incision. Chromatin immunoprecipitation assays demonstrated that the Pdyn and Bdnf promoters were more strongly associated with acetylated H3K9 after morphine plus incision than in the morphine or incision alone groups. Selective tropomyosin-related kinase B (ANA-12) and κ-opioid receptor (nor-binaltorphimine) antagonists were administered intrathecally, both reduced hyperalgesia one or three days after surgery. Administration of ANA-12 or nor-binaltorphimine attenuated the decreased morphine analgesic efficacy on day 1, but only nor-binaltorphimine was effective on day 3 after incision in opioid-exposed group. Coadministration of histone acetyltransferase inhibitor anacardic acid daily with morphine blocked the development of opioid-induced hyperalgesia and attenuated incision-enhanced hyperalgesia in morphine-treated mice. Anacardic acid had similar effects on analgesic tolerance, showing the involvement of histone acetylation in the interactions detected. Conclusions Spinal epigenetic changes
Lee, Bih-O; Liu, Yi; Wang, Yi-Hsien; Hsu, Hsin-Tien; Chen, Chien-Liang; Chou, Pi-Ling; Hsu, Wen-Chung
Family caregivers play an increasingly critical role in cancer patients' symptom management as the number of cancer patients receiving home care grows. However, there is a lack of research measuring the impact of the family caregivers' hesitancy to use analgesics on analgesic adherence and the resulting influence on patient pain intensity. To examine whether family caregivers' hesitancy to use analgesics is a mediator that influences patient adherence and investigate how analgesic regimen adherence affects pain intensity. This study used a cross-sectional and descriptive design. One hundred seventy-six patient-family caregiver dyads (N = 352) were recruited from one local hospital in southern Taiwan. Instruments included the Short Version of the Barriers Questionnaire-Taiwan, the Morisky Medication Adherence Measure-Taiwan, the Brief Pain Inventory-Chinese, and demographic and illness questionnaires. A one-way analysis of variance and post hoc comparisons were performed to assess the influence of analgesic regimen adherence on pain intensity. Sobel tests were used to examine mediating effects. Family caregivers' hesitancy to use analgesics was a significant mediator between patient barriers to use analgesics and patient analgesic regimen adherence (P < 0.0001). Patients with low and moderate adherence levels reported significantly higher levels of pain severity (F = 3.83, P < 0.05). This study showed that family caregivers' hesitancy to use analgesics was a significant mediator associated with their hesitancy to use analgesics and the patients' analgesic adherence. It is important for health care providers to consider family caregivers' hesitancy to use analgesics when attempting to improve adherence to pain management regimens in clinical practice. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.
Ahmad, N.; Grad, H. A.; Haas, D. A.; Aronson, K. J.; Jokovic, A.; Locker, D.
The evidence for the efficacy of nonopioid analgesics in the dental pain model was examined by conducting a meta-analysis. Studies were obtained by searching the literature from August 1996 back to 1975 using the terms pain, analgesics, and dentistry. This led to the review of 294 articles, of which 33 studies met the inclusion criteria. Pain scale results were transformed into a common percent scale and converted to N-weighted means with differences in efficacy considered significant using a 95% confidence interval. Collectively, therapeutic doses of the nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used in dentistry were significantly more efficacious than the combination of acetaminophen (600 or 650 mg) with codeine (60 mg). Similarly, specific doses of each of diflunisal, flurbiprofen, ibuprofen, and ketorolac were significantly more efficacious than the commonly used acetaminophen-codeine combination. These quantitative results show that particular NSAIDs may be more efficacious than the acetaminophen-codeine combination for relief of postoperative dental pain. PMID:9481955
Ömür, Dilek; Oğuzalp, Hüseyin; Kiraz, Hasan A.; Ekin, Serpil; Alan, Cabir; Ersay, Ahmet R.; Hancı, Volkan
Objectives: To evaluate the analgesic effect of transversus abdominis plane (TAP) block administered before varicocele surgery. Methods: This study was completed at the Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey, between January 2011 and April 2013. In a prospective, double blind, randomized, placebo controlled clinical study, 40 male patients scheduled for elective varicocele operations were randomized to group T (treatment group) or group C (controls). After receiving general anesthesia, group T received a TAP block using 20 mL 0.25% bupivacaine on the operation side, whereas group C received a control block using 20 mL 0.9% Sodium chloride. During the first 24 hours after surgery, the patient pain was evaluated using the visual analogue scale (VAS) at rest and while coughing. Postoperative patient controlled analgesia morphine consumption, VAS scores, and side effects were recorded. Results: Of 34 patients, Group T (n=18) had significantly lower VAS pain scores than Group C (n=16) both at rest and while coughing. The total morphine consumed was lower (7.7 ± 4.0) versus 21.6 ± 12.4 mg, p<0.001) in the 24 hours after surgery. Conclusion: As part of a multimodal analgesic regime after varicocelectomy surgery, morphine consumption and VAS pain scores were significantly lower among those receiving 20 mL 0.25% bupivacaine administered for a TAP block than among controls. PMID:27279511
Ide, Soichiro; Kasai, Shinya; Ikeda, Kazutaka
Narcotic analgesics have been widely used for management of severe pain, especially for cancer pain. Most of these drugs are opioids, and they show their analgesic effects by acting through opioid receptors. Significant individual differences in opioid sensitivity can hamper effective pain treatments and increase side effects, which is associated with decreased quality of life. It is thought that genetic factors may affect individual differences in opioid sensitivity. Recent studies using various inbred and knockout mice have revealed that the mu-opioid receptor (MOP) plays a mandatory role in the analgesic properties of opioids. There is also increasing evidence that differences in the sequence of the MOP gene might significantly affect the amount of MOP gene mRNA expression and sensitivity to opioids. Furthermore, it can be thought that individual differences in opioid sensitivity are caused by genetic differences in not only MOP but other biomolecules, such as endogenous opioid peptides, molecules related with metabolic process and second messenger systems. Rapid advances in this research field are leading to a better understanding of relationships between gene polymorphisms and opioid sensitivities, which, in turn, will allow us to more accurately predict opioid sensitivity and opioid requirements in individual patients.
Ramachandran, Satya Krishna; Haider, Naeem; Saran, Kelly A; Mathis, Michael; Kim, Joyce; Morris, Michelle; O'Reilly, Michael
To identify risk factors for life-threatening critical respiratory events occurring during parenteral analgesic therapy for acute postoperative pain. Retrospective, observational, cohort study. University hospital. The electronic records of patients with sudden-onset, life-threatening critical respiratory events during analgesic therapy for postoperative pain were studied. Critical respiratory event data were identified from the hospital risk management database between 8/1/2000 and 7/31//2007. Patients required rescue treatment with naloxone, endototracheal intubation, or cardiopulmonary resusucitation. Pediatric patients were excluded from the study. In addition to the event description (type of analgesia, opioid dose, patient monitoring data, time of day, and time from surgery), each patient's record was reviewed to extract co-morbidities and outcome data. Over the 6-year period, 32 patients experienced a postoperative critical respiratory event. Twenty-six events and three deaths occurred within the first 24 hours of opioid therapy. Four of 32 patients died. Congestive heart failure, postoperative acute renal failure, obstructive sleep apnea, cardiac dysrhythmia, diabetes mellitus, coronary artery disease, and hypertension were significant associations in adult patients. The first 24 hours after commencing opioid-based analgesic therapy represents a high risk period. Obstructive sleep apnea, deep levels of sedation, nocturnal presentation, and postoperative acute renal failure were seen in patients who died as a result of these critical respiratory events. Copyright © 2011 Elsevier Inc. All rights reserved.
de Morais, Bruno Salome; Cruvinel, Marcos Guilherme Cunha; Carneiro, Fabiano Soares; Lago, Flavio; Silva, Yerkes Pereira
The efficacy of posterior brachial plexus block for shoulder surgeries is demonstrated by different authors. However, there is no consensus on the ideal mass and volume of local anesthetic to be employed. The objetive of this study was to compare different volumes and masses of ropivacaine in posterior brachial plexus block in arthroscopic surgeries of the shoulder. Sixty patients > 18 years, physical status ASA I and II, scheduled for unilateral arthroscopic surgeries of the shoulder were randomly placed in three groups: A (10 mL to 0.5%), B (20 mL to 0.5%), C (5 mL to 1%). The block was performed with a 22G needle of 100 mm connected to neurostimulator, in a point 3 cm lateral to the midpoint of C6 and C7 interspace, being injected the solution corresponding to each group. The postoperative pain was evaluated at the recovery room and within the first 24 hours of the postoperative period. The groups were compared on length of time until the first complaint of pain, visual numeric scale (VNS) score and morphine consumption within the first 24 hours. There was no statistically significant difference between the three groups related to age, weight and height. There was no difference in length of time until the first complaint of pain, VNS scores over three and morphine consumption in the postoperative period between the groups. This study concluded that 5 mL of 1% ropivacaine promoted analgesic efficacy similar to 10 mL or 20 mL of 0.5% ropivacaine in the posterior brachial plexus block using neurostimulator. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.
Toygar, Pinar; Akkaya, Taylan; Ozkan, Derya; Ozel, Ozgür; Uslu, Ebru; Gümüş, Haluk
In this study, postoperative analgesic effects of intravenous paracetamol administration in lumbar discectomy patients were evaluated. After the approval of ethic committee, 90 patients undergoing lumbar disc hernia operation randomly divided into 3 groups. After standart general anesthesia, patients in group I received 1 gr i.v. paracetamol infusion 15 minutes before the induction, patients in group II received i.v. Paracetamol infusion started 15 minutes before the end of surgery. i.v morphine via PCA is used for postoperative analgesia maintenance and patients pain scores were assessed with VAS at 0., 1., 2., 3., 6., 12. and 24. hours. First analgesic requirement time, total morphine consumption and side effects were recorded. In group I and II, VAS scores, 24 h morphine consumption and first morphine requirement times were significantly different comparing to group III. As a result, we think that in lumbar discectomy cases preoperative administration of 1 gr paracetamol has no preemptive analgesic effect.
Dong, Chun-Shan; Lu, Yao; Zhang, Jun; Sun, Peng; Yu, Jun-Ma; Wu, Chao; Lu, Qiang
Abstract Postoperative spinal patients remain a challenge for provision of postoperative analgesia. Patient-controlled intravenous analgesia (PCIA) is a major method in reducing the severe pain after the surgery in our institution, but some adverse effects prevent the use of adequate dosage opioids. This study was determined using the probit analysis to investigate the optimal dose of dexmedetomidine (DEX) infusion for postoperative analgesia combined with sufentanil (SUF) in spine surgery. The dose of DEX needed to produce satisfactory analgesia conditions following combination of 3.0 μg/kg SUF in PCIA pump, which was diluted to 250 mL with a 4 mL/h as background infusion. Patients were recruited with age 35 to 65 years. The satisfactory criteria of postoperative analgesia were determined with a average satisfaction level of pain control, sedation, self-satisfaction, and adverse effects, among others. The dose of DEX was determined using the modified Dixon's up-and-down method (0.5 μg/kg as a step size). The first patient was test at 3.0 μg/kg DEX. The patient was assessed at 6, 12, 36 hours, and termination of PCIA following the continuous infusion of DEX-SUF mixture in PCIA after surgery. Twenty-five patients were enrolled by predetermined criteria. The optimal dose of DEX required for satisfactory analgesic was 4.33 (SD, 0.38) μg/kg combined with 3.0 μg/kg SUF via a PCIA volume of 250 mL by background infusion of 4 mL/h. Using probit analysis, the ED50 of DEX was 4.12 μg/kg (95% confidence limits 3.74–4.52 μg/kg) for satisfactory postoperative analgesic in spine surgery, the ED95 of DEX was 4.85 μg/kg (95% confidence limits 4.48–7.13 μg/kg). There was no report of somnolence or respiratory depression, relevant bradycardia or hypotension, or over sedation in this study. The optimal dose of DEX was 4.33 (0.38) μg/kg−1 combined with 3.0 μg/kg−1 SUF diluted to 250 mL with a background infusion of 4 mL/h for
Byrne, Kelly; Nolan, Aoife; Barnard, John; Tozer, Megan; Harris, David; Sleigh, Jamie
This study aimed to discover whether co-analgesia with tramadol or additional morphine was more effective for patients who still had severe pain despite being given 10 mg intravenous morphine in the post-anesthesia care unit (PACU). All eligible patients were consented and recruited to the trial pre-operatively, but only a small subgroup – whose pain was not successfully controlled (pain score 6/10 or more) after receiving 10 mg of morphine in the PACU—were then randomized to enter the trial and receive, in a double blinded fashion, the analgesic study drug; which consisted of either a further 10 mg of morphine, or 100 mg of tramadol, titrated intravenously to control their pain. The groups were compared as to: the time to readiness for discharge, the patient’s pain scores over time, and the presence of side effects. There was no statistically significant difference in any of the outcomes measured. The time to readiness for discharge from PACU was 119 minutes in the morphine group and 120 minutes in the tramadol group. However in approximately half the cases who entered the trial (i.e., where pain had not been controlled with the pre-enrollment baseline 10 mg of morphine in PACU) neither a further 10 mg of morphine nor 100 mg of tramadol effectively relieved the patient’s pain. We found no difference between additional morphine and co-analgesia with tramadol in this study. Patients who don’t respond to reasonable doses of opioids in PACU are very likely to be unresponsive to further opioids, and other non-opioid analgesic techniques (such as regional anesthesia) should be considered early in this group of patients.
Aghdam, Babak Abri; Golzari, Samad Eslam Jamal; Moghadaszadeh, Majid
Background Postoperative pulmonary complications and pain are important causes of postoperative morbidity following thoracotomy. This study aimed to compare the effects of fast track and conservative treatment regimens on patients undergoing thoracotomy. Materials and Methods In this randomized controlled clinical trial, we recruited 60 patients admitted to the thoracic ICU of Imam Reza Hospital in two matched groups of 30 patients each. Group 1 patients received fast track regimen randomly; whereas, group 2 cases randomly received conservative analgesic regimen after thoracotomy and pulmonary resection. The outcome was determined based on the incidence of pulmonary complications and reduction of post-thoracotomy pain in all patients with forced expiratory volume in one second (FEV1) <75% predicted value which was measured while the patients were in ICU. The length of ICU stay, thoracotomy pain, morbidity, pulmonary complications and mortality were compared in two groups. Results A total of 60 patients, 45 (75%) males and 15(25%) females with ASA class I-III were recruited in this study. Postoperative pulmonary complications were observed in 5 (16.7%) patients in group 1 versus 17 (56.7%) patients in group 2. There were statistically significant differences in development of postoperative pulmonary complications such as atelectasis and prolonged air leak between both groups (P< 0.001 and P = 0.003). There was also a statistically significant difference in the rate of preoperative FEV1 (p = 0.001) and ASA scoring (p = 0.01) and value of FEV1 < 75% predicted in the two groups. The difference in length of ICU stay in two groups was statistically significant (P= 0.003 and P = 0.017 in FEV1 < 75% group). Four patients in group 1 and 9 patients in group 2 had FEV1reduced to less than 75% of predicted value (p = 0.03). Conclusion Using fast track regimen reduced postoperative pain and incidence of some pulmonary complications significantly when compared to the
Kumar, Shashwat; Kishan, Anantha
Study Design This was a prospective, randomized, controlled trial comprising 60 patients undergoing lumbosacral spine (noninstrumentation/nonfusion) surgery. Purpose The purpose of this study was to evaluate the efficacy of 0.2% ropivacaine (20 mL) administered alone as a single, preoperative, caudal epidural block injection versus that of intravenous analgesics in providing effective postoperative analgesia to patients undergoing lumbosacral spine surgery. Overview of Literature Various studies have shown the effectiveness of a caudal epidural injection (bupivacaine or ropivacaine) in providing postoperative analgesia in combination with steroids or other analgesics. This study uniquely analyzed the efficacy of a single injection of caudal epidural ropivacaine in providing postoperative pain relief. Methods Sixty patients who were scheduled to undergo surgery for degenerative lumbar spine disease (noninstrumentation/nonfusion) were consecutively divided into two groups, group R (Study) and group I (Control). 30 group R patients received a caudal epidural block with 20 mL of 0.2% ropivacaine after the administration of general anesthesia. 30 group I patients received no preoperative analgesia. Intravenous analgesics were administered during the postoperative period after a complaint of pain. Various parameters indicating analgesic effect were recorded. Results There was a significant delay in the average time to the first demand for rescue analgesia in the study group, suggesting significantly better postoperative pain relief than that in the control group. In comparison with the control group, the study group also showed earlier ambulation with minimal adverse effects. The requirement for intraoperative fentanyl was higher in the control group than that in the study group. Conclusions Preemptive analgesia with a single epidural injection of ropivacaine is a safe, simple, and effective approach, providing better postoperative pain relief, facilitating early
Wei, Wei; Tian, Yanli; Zhao, Chunlei; Sui, Zhifu; Liu, Chang; Wang, Congmin; Yang, Rongya
Background Our study aimed to explore the association between β1-adrenoceptor (ADRB1) rs1801253 polymorphism and analgesic effect of fentanyl after cancer surgeries in Chinese Han populations. Material/Methods Postoperative fentanyl consumption of 120 patients for analgesia was recorded. Genotype distributions were detected by allele specific amplification-polymerase chain reaction (ASA-PCR) method. Postoperative pain was measured by visual analogue scale (VAS) method. Differences in postoperative VAS score and postoperative fentanyl consumption for analgesia in different genotype groups were compared by analysis of variance (ANOVA). Preoperative cold pressor-induced pain test was also performed to test the analgesic effect of fentanyl. Results Frequencies of Gly/Gly, Gly/Arg, Arg/Arg genotypes were 45.0%, 38.3%, and 16.7%, respectively, and passed the Hardy-Weinberg Equilibrium (HWE) test. The mean arterial pressure (MAP) and the heart rate (HR) had no significant differences at different times. After surgery, the VAS score and fentanyl consumption in Arg/Arg group were significantly higher than in other groups at the postoperative 2nd hour, but the differences were not obvious at the 4th hour, 24th hour, and the 48th hour. The results suggest that the Arg/Arg homozygote increased susceptibility to postoperative pain. The preoperative cold pressor-induced pain test suggested that individuals with Arg/Arg genotype showed worse analgesic effect of fentanyl compared to other genotypes. Conclusions In Chinese Han populations, ADRB1 rs1801253 polymorphism might be associated with the analgesic effect of fentanyl after cancer surgery. PMID:26694722
Law, P.Y.; Reggio, Patricia H.; Loh, H.H.
The use of opioid analgesics for pain has always been hampered by their many side effects; in particular, the addictive liability associated with chronic use. Recently, attempts to develop analgesic agents with reduced side effects have targeted either the putative opioid receptor splice variants or the receptor heterooligomers. This review discusses the potential for receptor splice variant- and the hetero-oligomer-based discovery of new opioid analgesics. We also examine an alternative approach of using receptor mutants for pain management. Finally, we discuss the role of the biased agonism observed and the recently reported opioid receptor crystal structures in guiding the future development of opioid analgesics PMID:23598157
Law, Ping-Yee; Reggio, Patricia H; Loh, Horace H
The use of opioid analgesics for pain has always been hampered by their many side effects; in particular, the addictive liability associated with chronic use. Recently, attempts to develop analgesic agents with reduced side effects have targeted either the putative opioid receptor splice variants or the receptor hetero-oligomers. This review discusses the potential for receptor splice variant- and the hetero-oligomer-based discovery of new opioid analgesics. We also examine an alternative approach of using receptor mutants for pain management. Finally, we discuss the role of the biased agonism observed and the recently reported opioid receptor crystal structures in guiding the future development of opioid analgesics.
Oreskovic, Zrinka; Bicanic, Goran; Hrabac, Pero; Tripkovic, Branko; Delimar, Domagoj
Metamizole use has been limited because of its risk of agranulocytosis. However, more recent literature seems to support its safety. This prospective, randomised, double-blind study was conducted to compare the analgesic effects of intravenous metamizole or intravenous paracetamol in combination with morphine PCA during the first 24 h following total hip arthroplasty. One hundred ten consecutive patients were selected for study. The two study groups were (A) metamizole, (B) paracetamol. Postoperative pain therapy was provided by Morphine PCA pump. In the first treatment group (A group), all patients received intravenous metamizole 1.5 g every 8 h during the first 24 postoperative hours. In the second treatment group (B group), all patients received intravenous paracetamol 1 g every 8 h during the first 24 postoperative hours. Postoperative pain intensity was measured 1, 2, 3, 4, 6, 8, 10, 14, 18, 22 h after the end of surgery by a VAS. Statistically significant differences in VAS pain values favoring metamizole were reported at 6-h (p = 0.038), 8-h (p = 0.036), 14-h (p = 0.011), 18-h (p < 0.001) and 22-h (p = 0.025) post-baseline. Mean cumulative pain values were 17.9 for metamizole and 30.6 for paracetamol. In this study, we have also shown excellent efficacy of paracetamol and metamizole combined with opioids, but metamizole proved to be a better analgesic than paracetamol. It is also necessary to mention the financial aspect considering that intravenous paracetamol is about ten times more expensive than an equivalent analgesic doses of intravenous metamizole.
Kizilkaya, M; Yildirim, O S; Ezirmik, N; Kursad, H; Karsan, O
In this double-blind randomized study, the analgesic effects of morphine alone and with methylprednisolone were examined in 72 patients undergoing arthroscopic knee surgery. At the end of arthroscopy, patients were allocated randomly to one of four groups to receive intra-articular administrations of saline, morphine 1 mg, morphine 5 mg or morphine 1 mg with methylprednisolone 40 mg. Preoperative and postoperative pain levels at rest and during movement (active flexion of the knee) were measured by a visual analogue scale (VAS). Postoperative analgesic requirements to alleviate pain were evaluated. Pain scores were significantly lower for the patients who received 5 mg morphine and 1 mg morphine with 40 mg methylprednisolone than for those who received saline or 1 mg morphine. This was accompanied by a decrease in the postoperative consumption of analgesics and prolongation of the duration of pain relief. This study confirms that the analgesic effect of morphine given intra-articularly is dose dependent and that combination of methylprednisolone with morphine has an additive effect on analgesia.
Postoperative Analgesic Efficacy of Bilateral Transversus Abdominis Plane Block in Patients Undergoing Midline Colorectal Surgeries Using Ropivacaine: A Randomized, Double-blind, Placebo-controlled Trial
Qazi, Nahida; Bhat, Wasim Mohammad; Iqbal, Malik Zaffar; Wani, Anisur Rehman; Gurcoo, Showkat A.; Rasool, Sahir
Background: Ultrasound-guided transversus abdominis plane (TAP) block is done as a part of multimodal analgesia for pain relief after abdominal surgeries. This prospective randomized, double-blind, placebo-controlled trial was conducted to evaluate the postoperative analgesic efficacy of bilateral TAP block in patients undergoing midline colorectal surgeries using ropivacaine. Materials and Methods: Eighty patients scheduled for elective colorectal surgeries involving midline abdominal wall incision under general anesthesia were enrolled in this prospective randomized controlled trial. Group A received TAP block with 20 ml of 0.2% ropivacaine on either side of the abdominal wall, and Group B received 20 ml of normal saline. The time to request for rescue analgesia, total analgesic consumption in 24 h, and satisfaction with the anesthetic technique were assessed. Results: The mean visual analog scale scores at rest and on coughing were higher in control group (P > 0.05). Time (min) to request for the first rescue analgesia was prolonged in study group compared to control group (P < 0.001). The total tramadol consumption in 24 h postoperatively was significantly high in control group (P < 0.001). Nausea/vomiting was more common in control group (P > 0.05). The level of satisfaction concerning postoperative pain control/anesthetic technique was higher in study group (P < 0.001). Conclusion: TAP block produces effective and prolonged postoperative analgesia in patients undergoing midline colorectal surgery. It is a technically simple block to perform with a high margin of safety. It produces a considerable reduction in mean intravenous postoperative tramadol requirements, reduction in postoperative pain scores, and increased time to first request for further analgesia, both at rest and on movement. PMID:28928585
Nedeljkovic, Srdjan S; Correll, Darin J; Bao, Xiaodong; Zamor, Natacha; Zeballos, Jose L; Zhang, Yi; Young, Mark J; Ledley, Johanna; Sorace, Jessica; Eng, Kristen; Hamsher, Carlyle P; Maniam, Rajivan; Chin, Jonathan W; Tsui, Becky; Cho, Sunyoung; Lee, Doo H
Introduction In spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially important. Patients after bowel surgery are assessed for rapid return of bowel function and opioids worsen ileus, nausea and constipation. We describe a prospective, double-blind, parallel group, placebo-controlled randomised controlled trial testing the hypothesis that a novel analgesic drug, VVZ -149, is safe and effective in improving pain compared with providing opioid analgesia alone among adults undergoing laparoscopic colorectal surgery. Methods and analysis Based on sample size calculations for primary outcome, we plan to enrol 120 participants. Adult patients without significant medical comorbidities or ongoing opioid use and who are undergoing laparoscopic colorectal surgery will be enrolled. Participants are randomly assigned to receive either VVZ-149 with intravenous (IV) hydromorphone patient-controlled analgesia (PCA) or the control intervention (IV PCA alone) in the postoperative period. The primary outcome is the Sum of Pain Intensity Difference over 8 hours (SPID-8 postdose). Participants receive VVZ-149 for 8 hours postoperatively to the primary study end point, after which they continue to be assessed for up to 24 hours. We measure opioid consumption, record pain intensity and pain relief, and evaluate the number of rescue doses and requests for opioid. To assess safety, we record sedation, nausea and vomiting, respiratory depression, laboratory tests and ECG readings after study drug administration. We evaluate for possible confounders of analgesic response, such as anxiety, depression and catastrophising behaviours. The study will also collect blood sample data and evaluate for pharmacokinetic and pharmacodynamic relationships. Ethics and dissemination Ethical approval of the study protocol has been obtained from
Chang, David J; Desjardins, Paul J; King, Thomas R; Erb, Tara; Geba, Gregory P
Our objective in this study was to compare the analgesic effects of etoricoxib and oxycodone/acetaminophen in a postoperative dental pain model. Patients experiencing moderate to severe pain after extraction of two or more third molars were randomized to single doses of etoricoxib 120 mg (n = 100), oxycodone/acetaminophen 10/650 mg (n = 100), or placebo (n = 25). The primary end-point was total pain relief over 6 h. Other end-points included patient global assessment of response to therapy; onset, peak, and duration of effect; and rescue opioid analgesic use. Active treatments were statistically significantly superior to placebo for all efficacy measures. Total pain relief over 6 h for etoricoxib was significantly more than for oxycodone/acetaminophen (P < 0.001). Patient global assessment of response to therapy at 6 and 24 h was superior for etoricoxib. Both drugs achieved rapid onset, although the time was faster for oxycodone/acetaminophen by 5 min. The peak effect was similar for both drugs. Compared with oxycodone/acetaminophen patients, etoricoxib patients experienced a longer analgesic duration, had a smaller percentage requiring rescue opioids during 6 and 24 h, and required less rescue analgesia during 6 and 24 h. Oxycodone/acetaminophen treatment resulted in more frequent adverse events (AEs), drug-related AEs, nausea, and vomiting compared with etoricoxib treatment. In conclusion, etoricoxib 120 mg provided superior overall efficacy compared with oxycodone/acetaminophen 10/650 mg and was associated with significantly fewer AEs.
Bellieni, C V; Cordelli, D M; Raffaelli, M; Ricci, B; Morgese, G; Buonocore, G
Aims To assess the analgesic effect of passive or active distraction during venipuncture in children. Methods We studied 69 children aged 7–12 years undergoing venipuncture. The children were randomly divided into three groups: a control group (C) without any distraction procedure, a group (M) in which mothers performed active distraction, and a TV group (TV) in which passive distraction (a TV cartoon) was used. Both mothers and children scored pain after the procedure. Results Main pain levels rated by the children were 23.04 (standard deviation (SD) 24.57), 17.39 (SD 21.36), and 8.91 (SD 8.65) for the C, M, and TV groups, respectively. Main pain levels rated by mothers were 21.30 (SD 19.9), 23.04 (SD 18.39), and 12.17 (SD 12.14) for the C, M, and TV groups, respectively. Scores assigned by mothers and children indicated that procedures performed during TV watching were less painful (p<0.05) than control or procedures performed during active distraction. Conclusion TV watching was more effective than active distraction. This was due either to the emotional participation of the mothers in the active procedure or to the distracting power of television. PMID:16920758
Bellieni, C V; Cordelli, D M; Raffaelli, M; Ricci, B; Morgese, G; Buonocore, G
To assess the analgesic effect of passive or active distraction during venipuncture in children. We studied 69 children aged 7-12 years undergoing venipuncture. The children were randomly divided into three groups: a control group (C) without any distraction procedure, a group (M) in which mothers performed active distraction, and a TV group (TV) in which passive distraction (a TV cartoon) was used. Both mothers and children scored pain after the procedure. Main pain levels rated by the children were 23.04 (standard deviation (SD) 24.57), 17.39 (SD 21.36), and 8.91 (SD 8.65) for the C, M, and TV groups, respectively. Main pain levels rated by mothers were 21.30 (SD 19.9), 23.04 (SD 18.39), and 12.17 (SD 12.14) for the C, M, and TV groups, respectively. Scores assigned by mothers and children indicated that procedures performed during TV watching were less painful (p<0.05) than control or procedures performed during active distraction. TV watching was more effective than active distraction. This was due either to the emotional participation of the mothers in the active procedure or to the distracting power of television.
Safety of lornoxicam in the treatment of postoperative pain: a post-marketing study of analgesic regimens containing lornoxicam compared with standard analgesic treatment in 3752 day-case surgery patients.
Rawal, Narinder; Krøner, Karsten; Simin-Geertsen, Marija; Hejl, Charlotte; Likar, Rudolf
Post-marketing surveillance studies can provide supplemental data on the safety of medications in the general population. This study aimed to evaluate the safety of analgesic regimens including the NSAID lornoxicam in the short-term treatment of postoperative pain in a clinically relevant population. Randomized, open-label, multicentre, multinational, observational cohort study of 4 days' duration. In-hospital postoperative setting, with discharge to home treatment within 24 hours of surgery. Adults aged > or =18 years expected to be in need of analgesic treatment after day-case surgery. Analgesic regimens containing lornoxicam were compared with a standard analgesic treatment, which was defined as the treatment that the patient would normally receive at the centre. Following day-case surgery, patients were provided with appropriate analgesic medication, and adverse events (AEs; defined as all recorded events with symptoms) were recorded by the investigator during the in-hospital stay and by the patient for the next 3 days using entries recorded morning and evening in a patient diary. Statistical analyses tested for between-treatment differences in AEs, adverse drug reactions (ADRs; defined as events probably, possibly or unlikely to be related to treatment) and gastrointestinal AEs (GI-AEs). A total of 4152 patients were randomized to treatment. Since 400 patients did not take any analgesic, the safety population consisted of 1838 patients for lornoxicam and 1914 patients for standard analgesic treatment. Demographic and disease characteristics were similar between the two treatment groups, as were the type of surgery and the anaesthesia used in surgery. In the safety population, 16.9% of patients received no analgesic in hospital, and when analgesics were provided they were often administered in combination. Similarly, approximately 17% of patients did not take any analgesics at home. AEs were reported in 27.1% and 29.4% of patients in the lornoxicam and standard
Postoperative consumption of opioid analgesics following correction of pectus excavatum is influenced by pectus severity: a single-centre study of 236 patients undergoing minimally invasive correction of pectus excavatum.
Grosen, Kasper; Pfeiffer-Jensen, Mogens; Pilegaard, Hans K
Surgical correction of pectus excavatum (PE) is primarily performed to achieve cosmetic and psychological benefits for the patient. Minimally invasive repair of PE is often associated with severe postoperative pain. This study estimates the effect of the severity of PE on the postoperative consumption of opioid analgesics following this procedure to optimise pain management. A retrospective study was conducted on 236 consecutive patients undergoing minimally invasive repair of PE from 2005 to 2008. The collected data included depth of preoperative pectus excavation, patient demographics, peri- and postoperative information, including data on pain management. The consumption of opioid analgesics was registered after discontinuation of epidural analgesia and other types of opioid analgesics used during the study period were converted to morphine equivalents. Multiple linear regression analysis was performed to estimate the effect of the severity of PE on the postoperative consumption of opioid analgesics and to adjust for potential confounding. The total morphine consumption following minimally invasive repair of PE ranged between 20 and 370 mg day(-1). Multiple linear regression analysis explained approximately 30% of the variation in daily morphine consumption (R-squared=0.2957). There was a significant positive linear relationship between pectus severity and the daily consumption of morphine. Thus, postoperative consumption of morphine increased by 6% (95% confidence interval (CI): 0.3-11%) when preoperative PE depth deteriorated with 1cm. This study confirms that pectus severity has a significant impact on the consumption of opioid analgesics following minimally invasive repair of PE. We conclude that knowledge of pectus severity might be useful in the prediction of the expected morphine consumption in future patients, especially during the critical transition period from epidural analgesia to oral analgesia. Copyright (c) 2009 European Association for Cardio
Eremenko, A A; Sorokina, L S; Pavlov, M V
A prospective, randomized, comparative study was conducted. 3 analgesia protocols were used: 1) patient controlled analgesia (PCA) with trimeperidine in combination with a nefopam constant infusion; 2) PCA with trimeperidine in combination with a nefopam bolus; 3) PCA with trimeperidine separately during early postoperative period in cardiac surgery patients. The study included 60 patients agedf rom 40 to 65 years of age (20 patients in each group). The analgesia efficacy was evaluated with a 5-point verbal rating scale (VRS) for pain intensity and inspiratory lung capacity (ILC), measured with incentive spirometer. The safety of nefopam during early postoperative period in cardiac surgery patients was shown. The combination of nefopam and trimeperidine led to a more pronounced analgetic effect. Trimeperidine consumption was significantly lower in nefopam groups than in the group of isolated PCA. Wholly adverse effects were associated with trimeperidine and were dose-related The incidence of nausea, vomiting, dizziness, weakness, bowel paresis was significantly higher in isolated PCA group than in the other two groups.
Deniz, Süleyman; Atım, Abdulkadir; Kürklü, Mustafa; Çaycı, Tuncer; Kurt, Ercan
In this study, we aimed to compare the postoperative analgesic efficiency of an ultrasound-guided fascia iliaca compartment block and a 3 in 1 block in patients who underwent hip prosthesis surgery as a result of hip fracture. With approval from the local ethics committee, 70 patients, aged 20 to 80, undergoing hip prosthesis surgery under elective conditions were included in this randomized, prospective, controlled study. They were informed of the patient-controlled analgesia (PCA) device and visual analog scale (VAS). All patients were separated randomly into three groups. Anaesthesia induction was standardized for all groups. An ultrasound guidance fascia iliaca compartment block (FICB) was applied to the first group before anaesthesia induction. For the second group, a 3 in 1 block was applied, while for the control group no block was applied. After incision on all patients, 20 mg tenoxicam and 1 mg/kg tramadol were injected intravenously. Following surgery, IV tramadol PCA was begun on all patients routinely. In our study, the presence of cortisol and ACTH levels, hemodinamical parameters, nausea and sedation were determined. We observed a decrease in VAS values and opioid consumption, no adverse effects on nausea and sedation, and a suppression of stress hormones in both the ultrasound-guided FICB and 3 in 1 block groups. We believe that the safe and efficient application of the ultrasound-guided 3 in 1 block and the FICB is necessary in multimodal analgesic treatment in order to enable postoperative analgesia in hip prosthesis surgery.
Moore, R Andrew; Derry, Sheena; Aldington, Dominic; Wiffen, Philip J
This is an update of a Cochrane overview published in Issue 9, 2011; that overview considered both efficacy and adverse events. This overview considers adverse events, with efficacy dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the adverse events associated with individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews. To provide an overview of adverse event rates associated with single-dose oral analgesics, compared with placebo, for acute postoperative pain in adults. We identified systematic reviews in The Cochrane Database of Systematic Reviews on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group. We extracted information related to participants experiencing any adverse event, and reports of serious adverse events, and deaths from the individual reviews. Information was available from 39 Cochrane reviews for 41 different analgesics or analgesic combinations (51 drug/dose/formulations) tested in single oral doses in participants with moderate or severe postoperative pain. This involved around 350 unique studies involving about 35,000 participants. Most studies involved younger participants with pain following removal of molar teeth.For most nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, and combinations not containing opioids, there were few examples where participants experienced significantly more or fewer adverse events than with placebo. For aspirin 1000 mg and diflunisal 1000 mg, opioids, or fixed-dose combination drugs containing opioids, participants typically experienced significantly more adverse events than with placebo. Studies of combinations of ibuprofen and paracetamol reported significantly fewer adverse events.Serious adverse events were rare, occurring a rate of about 1 in 3200 participants.Most reviews did not report specific adverse events. Despite
Campbell, Claudia M.; Witmer, Kenny; Simango, Mpepera; Carteret, Alene; Loggia, Marco L.; Campbell, James N.; Haythornthwaite, Jennifer A.; Edwards, Robert R.
Behavioral analgesic techniques such as distraction reduce pain in both clinical and experimental settings. Individuals differ in the magnitude of distraction-induced analgesia, and additional study is needed to identify the factors that influence the pain relieving effects of distraction. Catastrophizing, a set of negative emotional and cognitive processes, is widely recognized to be associated with increased reports of pain. We sought to evaluate the relationship between catastrophizing and distraction analgesia. Healthy participants completed three sessions in a randomized order. In one session (Pain Alone), pain was induced by topical application of a 10% capsaicin cream and simultaneous administration of a tonic heat stimulus. In another session (Pain + Distraction), identical capsaicin+heat application procedures were followed, but subjects played video games that required a high level of attention. During both sessions, verbal ratings of pain were obtained and participants rated their degree of catastrophizing. During the other session (Distraction Alone) subjects played the video games in the absence of any pain stimulus. Pain was rated significantly lower during the distraction session compared to the “pain alone” session. In addition, high catastrophizers rated pain significantly higher regardless of whether the subjects were distracted. Catastrophizing did not influence the overall degree of distraction analgesia; however, early in the session high catastrophizers had little distraction analgesia, though later in the session low and high catastrophizers rated pain similarly. These results suggest that both distraction and catastrophizing have substantial effects on experimental pain in normal subjects and these variables interact as a function of time. PMID:20188470
Campbell, Claudia M; Witmer, Kenny; Simango, Mpepera; Carteret, Alene; Loggia, Marco L; Campbell, James N; Haythornthwaite, Jennifer A; Edwards, Robert R
Behavioral analgesic techniques such as distraction reduce pain in both clinical and experimental settings. Individuals differ in the magnitude of distraction-induced analgesia, and additional study is needed to identify the factors that influence the pain relieving effects of distraction. Catastrophizing, a set of negative emotional and cognitive processes, is widely recognized to be associated with increased reports of pain. We sought to evaluate the relationship between catastrophizing and distraction analgesia. Healthy participants completed three sessions in a randomized order. In one session (Pain Alone), pain was induced by topical application of a 10% capsaicin cream and simultaneous administration of a tonic heat stimulus. In another session (Pain+Distraction), identical capsaicin+heat application procedures were followed, but subjects played video games that required a high level of attention. During both sessions, verbal ratings of pain were obtained and participants rated their degree of catastrophizing. During the other session (Distraction Alone) subjects played the video games in the absence of any pain stimulus. Pain was rated significantly lower during the distraction session compared to the "Pain Alone" session. In addition, high catastrophizers rated pain significantly higher regardless of whether the subjects were distracted. Catastrophizing did not influence the overall degree of distraction analgesia; however, early in the session high catastrophizers had little distraction analgesia, though later in the session low and high catastrophizers rated pain similarly. These results suggest that both distraction and catastrophizing have substantial effects on experimental pain in normal subjects and these variables interact as a function of time. Copyright 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Tugrul, S; Degirmenci, N; Eren, S B; Dogan, R; Veyseller, B; Ozturan, O
The aim of this study was to assess the analgesic, bleeding and nausea/vomiting effects of magnesium with and without metamizol on post-tonsillectomy patients. This prospective and randomised clinical trial included 54 patients aged 18-63 years who were scheduled for elective tonsillectomy. The patients were randomly divided into two groups and administered either magnesium with metamizol or only metamizol. They had been classified as physical status class I and II using the American Society of Anesthesiologists guidelines. All patients underwent the same surgical procedure performed by a single surgeon. The groups did not differ according to age, sex, or duration of anaesthesia or surgery. Postoperative pain, bleeding and nausea/vomiting were evaluated using the VAS and bleeding and nausea/vomiting scores on the first, fifth and tenth days. On the first, fifth and tenth postoperative days, the VAS scores of the magnesium with metamizol group were significantly lower than those of the metamizol-only group (p1 = 0.001; p5 = 0.015; p10 = 0.015). There were no significant differences in postoperative bleeding and nausea/vomiting scores between the two groups (p = 0.425 and p = 0.258, respectively). This study showed that magnesium enhanced the analgesic effect on post-tonsillectomy pain. Use of magnesium with an analgesic drug may be beneficial for management of post-tonsillectomy pain.
McEntire, Dan M; Kirkpatrick, Daniel R; Kerfeld, Mitchell J; Hambsch, Zakary J; Reisbig, Mark D; Agrawal, Devendra K; Youngblood, Charles F
The perioperative care of obstructive sleep apnea (OSA) patients is currently receiving much attention due to an increased risk for complications. It is established that postoperative changes in sleep architecture occur and this may have pathophysiological implications for OSA patients. Upper airway muscle activity decreases during rapid eye movement sleep (REMS). Severe OSA patients exhibit exaggerated chemoreceptor-driven ventilation during non-rapid eye movement sleep (NREMS), which leads to central and obstructive apnea. This article critically reviewed the literature relevant to preoperative screening for OSA, prevalence of OSA in surgical populations and changes in postoperative sleep architecture relevant to OSA patients. In particular, we addressed three questions in regard to the effects of sedative-hypnotics, anesthetics and analgesics on sleep architecture, the underlying mechanisms and the relevance to OSA. Indeed, these classes of drugs alter sleep architecture, which likely significantly contributes to abnormal postoperative sleep architecture, exacerbation of OSA and postoperative complications.
Mahajan, Rajesh; Grover, Vinod K; Chari, Pramila
To evaluate the analgesic efficacy and duration of varying doses of caudal neostigmine with plain bupivacaine and its side effects in children undergoing genito-urinary surgery. In a randomized double-blind prospective study 80 boys aged two to eight years scheduled for surgical repair of hypospadias were allocated randomly to one of four groups (n = 20 each) and received either only caudal 0.25% plain bupivacaine 0.5 mL.kg(-1) (Group I) or 0.25% plain bupivacaine 0.5 mL.kg(-1) with neostigmine (Groups II-IV) in doses of 2, 3 and 4 microg.kg(-1) respectively. Postoperative pain was assessed for 24 hr using an objective pain score. Blood pressure, heart rate, oxygen saturation, total amount of analgesic consumed and adverse effects were also recorded. The duration of postoperative analgesia in Group I (5.1 +/- 2.3 hr) was significantly shorter than in the other three groups (II -16.6 +/- 4.9 hr; III - 17.2 +/- 5.5 hr; IV - 17.0 +/- 5.8 hr; P < 0.05). Total analgesic (paracetamol) consumption was significantly more in Group I (697.6 +/- 240.7 mg) than in the groups receiving caudal neostigmine (II - 248.0 +/- 178.4; III - 270.2 +/- 180.8 and IV -230.6 +/- 166.9 mg; P < 0.05). Groups II, III and IV were comparable with regards to duration of postoperative analgesia and total analgesic consumption (P > 0.05). Incidence of nausea and vomiting were comparable in all four groups. No significant alteration in vital signs or any other adverse effects were observed. Caudal neostigmine (2, 3 and 4 microg.kg(-1)) with bupivacaine produces a dose-independent analgesic effect ( approximately 16-17 hr) in children as compared to those receiving caudal bupivacaine alone (approximately five hours) and a reduction in postoperative rescue analgesic consumption without increasing the incidence of adverse effects.
Bergmann, Hannes M; Nolte, Ingo; Kramer, Sabine
To compare analgesic efficacy of preoperative versus postoperative administration of carprofen and to determine, if preincisional mepivacaine epidural anesthesia improves postoperative analgesia in dogs treated with carprofen. Blind, randomized clinical study. Dogs with femoral (n=18) or pelvic (27) fractures. Dogs were grouped by restricted randomization into 4 groups: group 1 = carprofen (4 mg/kg subcutaneously) immediately before induction of anesthesia, no epidural anesthesia; group 2 = carprofen immediately after extubation, no epidural anesthesia; group 3 = carprofen immediately before induction, mepivacaine epidural block 15 minutes before surgical incision; and group 4 = mepivacaine epidural block 15 minutes before surgical incision, carprofen after extubation. All dogs were administered carprofen (4 mg/kg, subcutaneously, once daily) for 4 days after surgery. Physiologic variables, nociceptive threshold, lameness score, pain, and sedation (numerical rating scale [NRS], visual analog scale [VAS]), plasma glucose and cortisol concentration, renal function, and hemostatic variables were measured preoperatively and at various times after surgery. Dogs with VAS pain scores >30 were administered rescue analgesia. Group 3 and 4 dogs had significantly lower pain scores and amount of rescue analgesia compared with groups 1 and 2. VAS and NRS pain scores were not significantly different among groups 1 and 2 or among groups 3 and 4. There was no treatment effect on renal function and hemostatic variables. Preoperative carprofen combined with mepivacaine epidural anesthesia had superior postoperative analgesia compared with preoperative carprofen alone. When preoperative epidural anesthesia was performed, preoperative administration of carprofen did not improve postoperative analgesia compared with postoperative administration of carprofen. Preoperative administration of systemic opioid agonists in combination with regional anesthesia and postoperative administration
Huse, K; Stahl, H J; Krämer, M
Buprenorphin was given to 12 patients as a postoperative analgesic after neurosurgery, and the effects of the drug on the circulation, respiration and the electroencephalogram were studied. The circulation was not significantly affected, respiration was moderately depressed, the analgesic action was satisfactory. The depression of consciousness was reflected in the electroencephalographic pattern.
Akinci, Seda B; Saricaoğlu, Fatma; Atay, Ozgur Ahmet; Doral, Mahmut Nedim; Kanbak, Meral
The aim of the study was to compare the analgesic effect of 5 mg intra-articular (IA) morphine with 50 mg IA tramadol. Prospective double-blind randomized trial. Seventy-five patients having elective arthroscopic surgery of the knee were randomized to receive IA tramadol 50 mg (tramadol group), IA morphine 5 mg (morphine group), or IA normal saline (control group), in equivalent volumes (20 mL). The tourniquet was released 10 minutes after analgesic administration. Verbal pain rating score between 0 and 10 (VRS), supplemental analgesic requirements, and incidence of side effects were recorded postoperatively. Results are given as (median [5-95 percentiles]). The control group had a significantly shorter time to first analgesic request (25 min [15-55]) than morphine group, (34 min [15-158], P < .008) and the tramadol group, (33 min [17-728], P < .008). The patients in the control group complained of more severe pain (VRS 7 [4-10]) when they arrived at the postanesthesia care unit compared with the morphine group (VRS 1 [0-9], P = .002) and with the tramadol group (VRS 0 [0-9], P = .002). These treatment benefits were especially prominent in the patients who had meniscectomy or in the subgroup of patients with more than 6 months of preoperative pain. There was no statistical difference between the tramadol and morphine groups in the time to first analgesia, postoperative pain scores after arrival at the postanesthesia care unit, consumption of rescue analgesic, or side effects. We conclude that 50 mg IA tramadol provides analgesia equivalent to 5 mg IA morphine. Level II, randomized controlled trial that shows no significant difference and lacks narrow confidence intervals.
Smith, G M; Smith, P H
The separate and combined effects of doxylamine succinate (25 mg) and acetaminophen (1 gm) on sleep were studied by interview procedures and information from medical records of 2,931 postoperative patients. The sample contained 1,617 patients with mild or moderate pain and 1,314 who were free of pain. Each received either doxylamine alone (S), acetaminophen alone (A), a combination of both drugs (C), or placebo (P). Drug treatment was double blind and randomized separately for the pain and pain-free subsamples. Twelve measures of sleep were determined. C was more beneficial than S or A, and S and A were each superior to P. For all 12 sleep measures, the effect of the combination (C - P) approximated or exceeded the sum of the two separate effects (S - P) + (A - P). The presence of either drug tended to enhance the sleep benefit of the other. The sedative and analgesic benefits to sleep were at least additive, and some outcome measures suggested synergism. In the total sample, the contributions of sedative and analgesic similar. Among patients with pain, contributions of the analgesic surpassed those of the sedative. For patients free of pain, the sedative was better, but even pain-free patients had enhanced sleep after the analgesic. The analgesic, but not the sedative, reduced pain; the analgesic induced the feeling of being well rested and not tired; the sedative induced a feeling of being drugged. Nondrug variables (e.g., pain, sex, age, and sleep expectations) influenced sleep outcome at least as much as drugs, but randomization and the large sample prevented those extraneous variables from biasing drug comparisons.
Renner, Bertold; Clarke, Geoff; Grattan, Tim; Beisel, Angelika; Mueller, Christian; Werner, Ulrike; Kobal, Gerd; Brune, Kay
The aim of this study was to determine the analgesic effect of acetaminophen compared to a combination of both caffeine and acetaminophen or caffeine alone using tonic and phasic pain stimulation. Twenty-four subjects were treated orally with 1000 mg acetaminophen, 130 mg caffeine, and a combination of both in a 4-way crossover, double-blind, placebo-controlled study. Pharmacokinetics and analgesic effects were assessed by means of an experimental pain model based on pain-related cortical potentials after phasic stimulation of the nasal mucosa with CO(2) and based on pain ratings after tonic stimulation with dry air. Analgesic effects of acetaminophen and acetaminophen plus caffeine but not caffeine alone caused a significant reduction of pain-related cortical potentials beginning 30 minutes after medication. The combination demonstrated an enhanced effect throughout the observation time up to 3 hours. Caffeine accelerated acetaminophen absorption, indicated by enhanced early AUCs. Significant analgesic effects of the combination on tonic pain ratings were found throughout the observation time as compared to acetaminophen and placebo. In this study, caffeine enhanced and prolonged the analgesic activity of acetaminophen.
Tabaraki, Nasim; Shahbazzadeh, Delavar; Moradi, Ali Mashinchian; Vosughi, Gholamhossein; Mostafavi, Pargol Ghavam
Objective(s): Cone snails are estimated to consist of up to 700 species. The venom of these snails has yielded a rich source of novel peptides. This study was aimed to study the analgesic effect of Persian Gulf Conus textile and its comparison with morphine in mouse model. Materials and Methods: Samples were collected in Larak Island. The venom ducts were Isolated and kept on ice then homogenized. The mixture centrifuged at 10000 × g for 20 min. Supernatant was considered as extracted venom. The protein profile of venom determined using 15% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Venom was administered intraperitoneally (IP) to evaluate the LD50 in Swiss albino mice. Different concentrations of Conus textile venom were injected intrathecally to mice to evaluate their analgesic effect in comparison to morphine. Injection was carried out between the L5 and L6 vertebrae. Differences between groups in the first and second phase were tested with Two-Way analysis of variance (ANOVA). Results: SDS-PAGE indicated 12 bands ranged between 6 and 180 KDa. Finally, ten ng of Conus crude venom showed the best analgesic activity in formalin test. No death observed up to 100 mg/kg. Analgesic activity of crude venom was more significant (P<0.05) in acute pain than inflammatory pain. The analgesic effect of 10 ng Conus venom was the same as morphine for reduction of inflammatory pain (P=0.27). Conclusion: The venom of Persian Gulf Conus textile contains an analgesic component for reliving of acute pain which can lead to find an analgesic drug. PMID:25729549
Lee, Elizabeth; Teeple, Mary; Bagrodia, Naina; Hannallah, Jack; Yazzie, Nazhone P; Adamas-Rappaport, William J
Ethnic disparities in pain assessment and analgesic administration following surgery have received little attention in the surgery literature. We noted that our Native American patients were less likely than others to complain of pain. A retrospective chart review of 21 Native American patients and a control group who underwent outpatient, elective laparoscopic cholecystectomy was performed. Native American patients had a statistically lower numeric pain score (mean, 6.5; 95% CI, 3.6-9.4) than non-Native American patients (mean, 8.1; 95% CI, 6.3-9.9; t38 = 2.63; P < .05). Native American patients also received less postsurgical analgesic (mean, 7.4; 95% CI, 4.0-10.8) than non-Native American patients (mean, 11.2; 95% CI, 7.2-15.2; t38 = 3.07; P < .01). Medical staff attending Native American patients should be aware that response to some scales to assess pain may not reflect accurately the degree of pain experienced.
Holgado, Darias; Hopker, James; Sanabria, Daniel; Zabala, Mikel
Analgesics are used widely in sport to treat pain and inflammation associated with injury. However, there is growing evidence that some athletes might be taking these substances in an attempt to enhance performance. Although the pharmacologic action of analgesics and their use in treating pain with and without anti-inflammatory effect is well established, their effect on sport performance is debated. The aim of this review was to evaluate the evidence of whether analgesics are capable of enhancing exercise performance and, if so, to what extent. Paracetamol has been suggested to improve endurance and repeated sprint exercise performance by reducing the activation of higher brain structures involved in pain and cognitive/affective processing. Nonsteroidal anti-inflammatory drugs affect both central and peripheral body systems, but investigation on their ergogenic effect on muscle strength development has provided equivocal results. The therapeutic use of glucocorticoids is indubitable, but clear evidence exists for a performance-enhancing effect after short-term oral administration. Based on the evidence presented in this review article, the ergogenic benefit of analgesics may warrant further consideration by regulatory bodies. In contrast to the aforementioned analgesics, there is a paucity of research on the use of opioids such as tramadol on sporting performance. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.
Randomised, double-blind, parallel group, placebo-controlled study to evaluate the analgesic efficacy and safety of VVZ-149 injections for postoperative pain following laparoscopic colorectal surgery.
Nedeljkovic, Srdjan S; Correll, Darin J; Bao, Xiaodong; Zamor, Natacha; Zeballos, Jose L; Zhang, Yi; Young, Mark J; Ledley, Johanna; Sorace, Jessica; Eng, Kristen; Hamsher, Carlyle P; Maniam, Rajivan; Chin, Jonathan W; Tsui, Becky; Cho, Sunyoung; Lee, Doo H
In spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially important. Patients after bowel surgery are assessed for rapid return of bowel function and opioids worsen ileus, nausea and constipation. We describe a prospective, double-blind, parallel group, placebo-controlled randomised controlled trial testing the hypothesis that a novel analgesic drug, VVZ -149, is safe and effective in improving pain compared with providing opioid analgesia alone among adults undergoing laparoscopic colorectal surgery. Based on sample size calculations for primary outcome, we plan to enrol 120 participants. Adult patients without significant medical comorbidities or ongoing opioid use and who are undergoing laparoscopic colorectal surgery will be enrolled. Participants are randomly assigned to receive either VVZ-149 with intravenous (IV) hydromorphone patient-controlled analgesia (PCA) or the control intervention (IV PCA alone) in the postoperative period. The primary outcome is the Sum of Pain Intensity Difference over 8 hours (SPID-8 postdose). Participants receive VVZ-149 for 8 hours postoperatively to the primary study end point, after which they continue to be assessed for up to 24 hours. We measure opioid consumption, record pain intensity and pain relief, and evaluate the number of rescue doses and requests for opioid. To assess safety, we record sedation, nausea and vomiting, respiratory depression, laboratory tests and ECG readings after study drug administration. We evaluate for possible confounders of analgesic response, such as anxiety, depression and catastrophising behaviours. The study will also collect blood sample data and evaluate for pharmacokinetic and pharmacodynamic relationships. Ethical approval of the study protocol has been obtained from Institutional Review Boards at the participating institutions
Hoenicka, Markus; Gorki, Hagen; Traeger, Karl; Liebold, Andreas
Metamizole (dipyrone) is a first-line, non-opioid analgesic used for postoperative pain management. Clinical data and animal experiments indicate a possible vasodilator action of this drug. We investigated the effects of metamizole on human artery and vein tone in an ex vivo model to assess potential contributions to venous pooling. Excess segments of bypass grafts were harvested during coronary artery bypass grafting procedures. Tensions were measured in an organ bath for 120 min after adding metamizole to the preconstricted vessels. Contribution of endothelium was assessed in endothelium-denuded vessels, and indometacin was used to identify cyclooxygenase-mediated effects. Internal mammary arteries (n = 6) constricted after addition of 1, 3, and 10 μM metamizole and remained constricted at the lower doses. Transient constrictions also occurred in saphenous veins (n = 20), but veins relaxed below solvent controls after 20 min at all concentrations. Endothelium removal (n = 12) and cyclooxygenase inhibition (n = 12) suppressed the vasoconstrictor effect but not the vasodilator effect. Metamizole and its metabolites display counteracting effects on blood vessel tone ex vivo. The vasoconstrictor effect is mediated by cyclooxygenase-derived products. The net effect is site-specific, resulting in a selective venous vasodilator action. This may exacerbate unwanted venous pooling during postoperative pain therapy.
Rane, K; Sollevi, A; Segerdahl, M
Adenosine (Ado) is known, from studies in both animals and humans, to produce antinociception when administered systemically or intrathecally (IT). The current aim was to evaluate, in a placebo-controlled, randomised, double-blind study, whether IT adenosine given before surgery could reduce anaesthetic requirement and the need of opioids during 48 h after visceral surgery. Forty women (37-66 years, ASA I and II) scheduled for elective hysterectomy were included. Before inducing the standardised O2/N2O/isoflurane/fentanyl anaesthesia, the patients received an IT injection of either adenosine (500 microg in 1 ml volume) or placebo 1 ml (saline). Intraoperative anaesthetic drug doses and haemodynamics were recorded. Postoperative pain was assessed by visual analogue scale. For postoperative analgesia, cetobemidone was provided via intravenous patient-controlled analgesia (PCA). During surgery, there were no differences between groups in anaesthetic requirement or haemodynamic parameters. Postoperative cetobemidone requirements were similar in both groups (median 48 mg for adenosine/50 mg for saline) during the first 48 postoperative hours. IT adenosine did not influence the requirement of anaesthetic drug or postoperative analgesics after hysterectomy.
Kamkar Asl, Mina; Nazariborun, Ashraf; Hosseini, Mahmoud
Objective: The beneficial effects of clove on toothache have been well documented. We have also previously shown the analgesic effects of clove essential oil. The present work was done to investigate the analgesic effects of the aqueous extract of clove using hot plate test. The possible role of opioid receptors in the analgesic effects of clove was also investigated using naloxone. Materials and Methods: Ninety male mice were divided into nine groups: (1) Saline, (2-4) Aaqueous (Aq 50, Aq 100, and Aq 200) groups which were treated with 50, 100, and 200 mg/kg of aqueous extract of clove, respectively, (5-7) Ethanolic (Eth 50, Eth 100, and Eth 200) groups which were treated with 50, 100, and 200 mg/kg of ethanolic extract of clove, respectively, and (8-9) Aq 100- Naloxone and Aq 200- Naloxone which were pretreated with 4 mg/kg of naloxone before injection of 100 or 200 mg/kg of the aqueous extract. The hot plate test was performed as a base record 10 min before injection of drugs and consequently repeated every 10 minutes after the injection. Results: The maximal percent effect (MPE) in the animal groups treated with 50, 100, and 200 mg/kg of aqueous extract was significantly higher than the control group. Pretreatment with naloxone reduced the analgesic effects of both 100 and 200 mg/kg of the aqueous extract. Administration of all three doses of the ethanloic extract also non-significantly increased the MPE. Conclusion: The results of the present study showed that aqueous extract of clove has analgesic effect in mice demonstrated by hot plate test which is reversible by naloxone. The role of opioid system in the analgesic effect of clove might be suggested. However, more investigations are needed to elucidate the exact mechanism(s). PMID:25050273
Gutta, Rajesh; Koehn, Christopher R; James, Laura E
To examine the effect of ketorolac used as preemptive analgesia on the intensity of pain and analgesic requirements in the postoperative period. The present study was a randomized, double-blind, control study involving human subjects who underwent extraction of the mandibular third molars under intravenous anesthesia. The study group received 30 mg of intravenous ketorolac preoperatively, and the control group received a placebo. The pain intensity was measured using a visual analog scale. The decrease in postoperative pain was measured as the primary outcome variable. The interval to the first dose of analgesic, total analgesic requirements, and the global assessment were measured as secondary outcomes. The data were analyzed using the Student t test, Wilcoxon rank sum test, and χ(2) test. A total of 85 adult subjects, American Society of Anesthesiologists class I and II, participated in the present study. Randomization was effective, as shown by the absence of differences in the study variables between the 2 groups. Of the 85 patients, 29 were men and 56 were women. The average patient age was 22.6 years in the study group and 24 years in the control group. Those in the ketorolac group recorded lower visual analog scale pain scores at all intervals. However, the difference was statistically significant at the 4-hour interval (P = .01). The median interval to the use of rescue medication in the ketorolac group was 9.5 hours compared with 7 hours in the control group. However, no statistically significant difference was found in the interval to the rescue analgesic between the 2 groups (P = .39). No statistically significant difference was noted in the total amount of postoperative analgesics required in the first 72 hours between the 2 groups (P = .54). Also, no difference was seen in the global assessment between the 2 groups (P = .22). Those who received 30 mg of intravenous ketorolac preoperatively had less pain in the early (8-hour) postoperative period. The
Park, Hue Jung; Park, Je Uk; Yoo, Woojoo; Moon, Young Eun
Many studies have examined the postoperative analgesic effects of nefopam in various settings. However, although nefopam is expected to be useful in bimaxillary osteotomy, no published data are available. We divided 42 patients into nefopam [n = 21, nefopam 20 mg intravenous (i.v.) 30 min before surgery, followed by an i.v. infusion (5 mg/h) beginning immediately postoperatively for 24 h] and control [n = 21, normal saline] groups. Then we compared the analgesic efficacy, side effects, and degree of patient satisfaction with postoperative analgesia. Pain was lower in the nefopam group than in the controls in the recovery room [4.6 (3.0-6.0) vs. 6.0 (5.5-7.0), median (interquartile range), P = 0.002] and on the ward. Fewer patients in the nefopam group required rescue analgesics, and the degree of patient satisfaction was significantly higher in the nefopam group (P < 0.001). There were no significant differences in other side effects between the groups. However, the control group showed more sedation 1 h postoperatively (P = 0.009). Nefopam is an effective analgesic in bimaxillary osteotomy in that it can reduce the use of opioids and nonsteroidal anti-inflammatory drugs, thereby reducing the side effects of conventional analgesics. ( ClinicalTrials.gov (NCT 01461031)). Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Kukushkin, M L; Igon'kina, S I; Potapov, S V; Potapov, A V
The analgesic effects of inert gas xenon were examined on rats. The formalin model of inflammatory pain, tail-flick test, and hot-plate test revealed the antinociceptive effects of subanesthetizing doses of inhalation anesthetic xenon. Inhalation of 50/50 xenon/oxygen mixture moderated the nociceptive responses during acute and tonic phases of inflammatory pain.
Sufentanil infusion before extubation suppresses coughing on emergence without delaying extubation time and reduces postoperative analgesic requirement without increasing nausea and vomiting after desflurane anesthesia
Lee, Jea Yeun; Lim, Byung Gun; Park, Hye Yoon
Background Coughing, hypertension, tachycardia, and even laryngospasm can occur due to airway irritation during emergence from anesthesia. We investigated the effect of maintaining a sufentanil infusion during emergence from anesthesia by evaluating the incidence of cough and recovery profiles at extubation. Methods In total, eighty-four patients undergoing an elective laparoscopic hysterectomy were randomly divided into two sufentanil groups and a control group. During emergence, sufentanil was administered in the sufentanil groups at a rate of 0.2 µg/kg/hr (Group S1) or 0.3 µg/kg/hr (Group S2), and saline was administered to the control group. Cough score, hemodynamic changes, and recovery profiles, such as duration from skin closure to a bispectral index of 80, to eye opening at verbal command, to tracheal extubation and the total duration of study solution infusion, were recorded. The pain score, the total volume of administered patient-controlled analgesia (PCA), and the postoperative nausea and vomiting (PONV) score were evaluated 1, 6, and 24 hours after surgery. Results Groups S1 and S2 showed significantly lower cough scores and smaller hemodynamic changes on extubation compared to Group C. Recovery profiles showed no significant differences among the three groups. Pain score, PONV at 1 hour postoperatively, and the total volume of PCA administered at all evaluation times were significantly lower in Groups S1 and S2 than in the control group. However, pain score, and PONV at 6 hours and 24 hours postoperatively showed no significant differences. Conclusions A sufentanil infusion (0.2-0.3 µg/kg/hr) during emergence from desflurane anesthesia may suppress coughing on extubation in patients with body mass indexes (BMI) of 21-26 without delaying extubation time. It may also reduce the postoperative analgesic requirement without increasing PONV. PMID:22778885
Kashefi, Parviz; Montazeri, Kamran; Honarmand, Azim; Safavi, Mohammadreza; Hosseini, Hashem Mirzaee
BACKGROUND: Midazolam has analgesic properties. The aim of the present study was to assess the analgesic effect of midazolam when added to lidocaine in intravenous regional anesthesia (IVRA). METHODS: Sixty patients undergoing hand surgery were randomly allocated into two groups to receive 3 mg/kg 2% lidocaine diluted with saline to a total volume of 40 mL in the control group (group lidocaine saline ~ LS, n=30) or 50 μg/kg midazolam plus 3 mg/kg 2% lidocaine diluted with saline to a total volume of 40 mL in the midazolam group (group lidocaine midazolam ~ LM, n=30). Before and after the tourniquet application, hemodynamic variables, tourniquet pain, sedation, and analgesic use were recorded. RESULTS: Shortened sensory and motor block onset time [4.20 (0.84) vs. 5.94 (0.83) min, p = 0.001 and 6.99 (0.72) vs. 9.07 (0.99) min, p = 0.001 in LM and LS groups, respectively], prolonged sensory and motor block recovery times [8.41 (0.94) vs. 5.68 (0.90) min, p = 0.001 and 11.85 (1.18) vs. 7.06 (0.82) min, p = 0.001 in LM and LS groups, respectively], shortened visual analog scale (VAS) scores of tourniquet pain (p < 0.05), and improved quality of anesthesia were found in group LM (p < 0.05). VAS scores were lower in group LM in the postoperative period (p = 0.001). Postoperative analgesic requirements were significantly smaller in group LM (p = 0.001). CONCLUSIONS: The addition of 50 μg/kg midazolam to lidocaine for IVRA shortens the onset of sensory and motor block, and improves quality of anesthesia and perioperative analgesia without causing side effects. PMID:22973382
Han, Young Min; Woo, Sang-Uk; Choi, Min Sun; Park, Yu Na; Kim, Seung Hyun; Yim, Hyungshin; Yoo, Hye Hyun
Eurycoma longifolia is one of the most popular herbal medicines in Southeast Asia. The purpose of this study is to evaluate the analgesic and anti-inflammatory effects of the methanolic extract of E. longifolia roots (TA) in vivo and to investigate the underlying mechanisms. TA was tested for analgesic activity by the hot plate test and acetic acid test in mice. The anti-inflammatory effect of TA was observed in carrageenan-induced paw edema in mice. The in vitro molecular study using macrophage cells was performed to elucidate the relevant mechanism. The analgesic activity of 400 mg/kg TA was higher than that of aspirin in the hot plate test. TA also showed analgesic effects in the acetic acid test in a dose-dependent manner. In carrageenan-induced edema in mice, TA showed an anti-inflammatory effect comparable to that of diclofenac. Further in vitro molecular study using macrophage cells revealed that TA suppressed NF-κB translocation to the nucleus, leading to inactivation of the NF-κB signaling pathway and reduction in the expression of cyclooxygenase-2 and inducible nitric oxide synthase. These results exhibited the beneficial effects of TA for alleviating pain and inflammation, which were exerted through inactivation of the NF-κB signaling pathway.
Abdulla, S; Eckhardt, R; Netter, U; Abdulla, W
Following laparoscopic cholecystectomy, an effective post-operative pain control is necessary, at least during the first 24 hours. We present a randomized, double-blind trial on the effect of the combined use of intravenous parecoxib, and metamizol or paracetamol on piritramide consumption using a patient-controlled analgesia (PCA) pump in patients recovering from laparoscopic cholecystectomy. 120 patients were randomly allocated to four patient groups treated with normal saline or one of non-opioid analgesics (parecoxib 40 mg twice daily, metamizol 1 g three times daily, paracetamol 1 g three times daily) in addition to piritramide using the PCA pump. Beginning in the post-anesthesia care unit (PACU), patients were asked every 2 h for 6 hours and afterwards once every 6 h to quantify their pain experience at rest while piritramide consumption was recorded. In all groups, piritramide consumption was high in PACU. Only metamizol significantly reduced piritramide consumption compared to the others upon discharge from PACU. Overall, cumulative piritramide consumption was slightly lower in the metamizol group and higher in the NaCl group; however, these findings were statistically not significant. VAS scores were highest upon arrival in PACU and dropped almost continuously after surgery. A significantly lower postoperative pain intensity was only found in the parecoxib group at 24 h after surgery compared to the metamizol group. The efficacy of tested additive medications on piritramide consumption and pain relief is weak and there is no clear-cut difference between the non-opioid drugs used.
Efficacy of post-operative analgesia after posterior lumbar instrumented fusion for degenerative disc disease: a prospective randomized comparison of epidural catheter and intravenous administration of analgesics
Kluba, Torsten; Hofmann, Fabian; Bredanger, Sabine; Blumenstock, Gunnar; Niemeyer, Thomas
This prospective study aimed to compare the efficacy of epidural (EDA) versus intravenous (PCA) application of analgesics after lumbar fusion. Fifty-two patients scheduled for elective posterior instrumented lumbar fusion were randomized into two groups. EDA patients received an epidural catheter intraoperatively, and administration of ropivacain and sulfentanil was started after a normal postoperative wake-up test in the recovery room area. PCA patients received intravenous opioids in the post-operative period. Differences between EDA and PCA groups in terms of patient satisfaction with respect to pain relief were not significant. Nevertheless, EDA patients reported less pain on the third day after surgery. There were significantly more side effects in the EDA group, including complete reversible loss of sensory function and motor weakness. There were no major side effects, such as infection or persisting neurological deficits, in either group. The routine use of epidural anesthesia for lumbar spine surgery has too many risks and offers very little advantage over PCA. PMID:21808704
Murdoch, F R; Maker, G L; Nitsos, I; Polglase, G R; Musk, G C
The absorption of medetomidine released by continuous infusion from an osmotic pump in the abdominal cavity was studied in pregnant sheep during the 24 h postoperative period. Additionally pain and sedation was assessed. Eleven sheep were studied: six were treated with a medetomidine loaded osmotic pump delivering 10 µL/h (3 µg/kg/h medetomidine); and five with a saline loaded osmotic pump (control). Serial blood samples were taken and analysed to determine plasma medetomidine levels. Medetomidine was absorbed from the peritoneal cavity and a steady plasma concentration was achieved within 10 h, mean (SD) peak concentration was 2.87 (0.22) ng/mL. Sheep receiving medetomidine analgesia had significantly lower pain scores at 10 h than controls. Four control sheep required rescue analgesia, compared with 0 in the treatment group. Delivery of 3 µg/kg/h medetomidine by an intraperitoneal osmotic pump to pregnant sheep in the 24 h postoperative period provides adequate plasma concentrations of medetomidine for analgesia without sedation.
Wang, Ying; Chen, Yinghong; Xu, Hong; Luo, Haoming; Jiang, Ruizhi
The root of Panax ginseng C.A. Mey has various beneficial pharmacological effects. The present study aimed to evaluate the analgesic activities of glycoproteins from the root of Panax ginseng C.A. Mey in mice. Glycoproteins were isolated and purified from the root of Panax ginseng C.A. Mey. Physicochemical properties and molecular mass were determined by chemical assay and HPLC. Acetic acid-induced writhing and hot-plate tests were employed to study the analgesic effect of glycoproteins and compared with that of aspirin or morphine. The locomotor activity was tested in mice by using actophometer. Four glycoproteins were obtained. The glycoproteins which protein content was the highest (73.04%) displayed dose-dependent analgesic effect. In writhing test, the glycoproteins significantly inhibited writhes (P<0.001) at the dose of 20 mg/kg by intraperitoneal injection. In hot-plate test, only at the dose of 20 mg/kg prolong the hot-plate latency (P<0.05, at 30 min). In the locomotor activity test, the glycoproteins were significant decrease of motility counts at the dose of 20 and 40 mg/kg. These findings collectively indicate that the glycoproteins from the root of Panax ginseng C.A. Mey exhibited significant analgesic activities and the proteins were the active site, providing evidence for its pharmacal use. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Choi, Geun Joo; Kang, Hyun; Kim, Won Joong; Kwon, Ji Wung; Kim, Beom Gyu; Choi, Yoo Shin; Cha, Young Joo; Ko, Jin Soo
The purpose of this study was to evaluate the analgesic effect of Rubus occidentalis extract (ROE) in a rat model of incisional pain. The involved mechanisms and proinflammatory cytokine response were also examined. To investigate the analgesic effect, rats were intraperitoneally administered with normal saline or various doses of ROE before or after a plantar incision. To evaluate the involved mechanism, rats were intraperitoneally administered yohimbine, dexmedetomidine, prazosin, naloxone, atropine, or mecamylamine after a plantar incision; ROE was then administered intraperitoneally. The mechanical withdrawal threshold (MWT) was tested with von Frey filaments at various time points. To determine the inflammatory response, serum levels of interleukin (IL)-1β or IL-6 were measured. The MWTs significantly increased at 15 min after postincisional administration of 300 mg/kg ROE when compared with those in the control group. This elevation was observed for up to 45 min. Overall, MWTs increased in proportion to ROE dosage; however, ROEs administered before the incision produced no significant change in the MWT. The analgesic effect of ROE was significantly antagonized by mecamylamine, naloxone, and yohimbine, and agonized by dexmedetomidine. Administration of ROE inhibited the postincisional increase in serum IL-1β and IL-6. Intraperitoneal administration of ROE after surgery induces antinociceptive effects in a rat model of postoperative pain, and its effects on mechanical hyperalgesia may be associated with α2-adrenergic, nicotinic cholinergic, and opioid receptors. Copyright © 2016 Elsevier Inc. All rights reserved.
Bukhari, I A; Pivac, N; Alhumayyd, M S; Mahesar, A L; Gilani, A H
Piperine, is the major active principal of black pepper. In traditional medicine, black pepper has been used as an analgesic, anti-inflammatory agent and in the treatment of epilepsy. This study was conducted to evaluate the in vivo analgesic and anticonvulsant effects of piperine in mice. The analgesic and anticonvulsant effects of piperine were studied in mice using acetic acid-induced writhing, tail flick assay, pentylenetetrazole (PTZ)- and picrotoxin (PIC)-induced seizures models. The intraperitoneal (i.p.) administration of piperine (30, 50 and 70 mg/kg) significantly inhibited (P<0.01) the acetic acid-induced writhing in mice, similar to the effect of indomethacin (20 mg/kg i.p.). In the tail flick assay, piperine (30 and 50 mg/kg, i.p.) and morphine (5 mg/kg, i.p.) caused a significant increase (P<0.01) in the reaction time of mice. Pre-treatment of animals with naloxone (5 mg/kg i.p.), reversed the analgesic effects of both piperine and morphine in the tail flick assay. Piperine (30, 50 and 70 mg/kg, i.p.) and standard drugs, valproic acid (200 mg/kg, i.p.), carbamazepine (30 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) significantly (P<0.01) delayed the onset of PTZ-and PIC-induced seizures in mice. These findings indicate that piperine exhibits analgesic and anticonvulsant effects possibly mediated via opioid and GABA-ergic pathways respectively. Moreover, piperine being the main constituent of black pepper, may be contributing factor in the medicinal uses of black pepper in pain and epilepsy.
Kim, So Yeon; Kim, Nam Kyu; Baik, Seung Hyuk; Min, Byung Soh; Hur, Hyuk; Lee, Jinae; Noh, Hyun-young; Lee, Jong Ho; Koo, Bon-Neyo
Abstract There has been a rising interest in the possible association between perioperative opioid use and postoperative outcomes in cancer patients. Continuous surgical wound infiltration with local anesthetics is a nonopioid analgesic technique that can be used as a postoperative pain management alternative to opioid-based intravenous patient-controlled analgesia (IV PCA). The aim of this study was to compare the effects of an opioid-based analgesic regimen versus a local anesthetic wound infiltration-based analgesic regimen on immune modulation and short-term cancer recurrence or metastasis in patients undergoing laparoscopic resection of colorectal cancer. Sixty patients undergoing laparoscopic resection of colorectal cancer were randomly assigned to either the opioid group or the ON-Q group. For postoperative analgesia during the first 48 hours, the opioid group (n = 30) received fentanyl via IV PCA, whereas the ON-Q group (n = 30) received continuous wound infiltration of 0.5% ropivacaine with an ON-Q pump and tramadol via IV PCA. Pethidine for the opioid group and ketorolac or propacetamol for the ON-Q group were used as rescue analgesics. Anesthesia was induced and maintained with propofol and remifentanil. The primary outcome was postoperative immune function assessed by natural killer cell cytotoxicity (NKCC) and interleukin-2. Secondary outcomes were postoperative complications, cancer recurrence, or metastasis within 1 year after surgery, and postoperative inflammatory responses measured by white blood cell count, neutrophil percentage, and C-reactive protein. Immune function and inflammatory responses were measured before surgery and 24 and 48 hours after surgery. Fifty-nine patients completed the study. In the circumstance of similar pain control efficacy between the opioid group and the ON-Q group, postoperative NKCC and interleukin-2 levels did not differ between the 2 groups. The incidence of postoperative complications and recurrence
Dogan, Serpil Dagdelen; Ustun, Faik Emre; Sener, Elif Bengi; Koksal, Ersin; Ustun, Yasemin Burcu; Kaya, Cengiz; Ozkan, Fatih
We compared the effects of lidocaine and esmolol infusions on intraoperative hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery in laparoscopic cholecystectomy surgery. The first group (n=30) received IV lidocaine infusions at a rate of 1.5mg/kg/min and the second group (n=30) received IV esmolol infusions at a rate of 1mg/kg/min. Hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery characteristics were evaluated. In the lidocaine group, systolic arterial blood pressures values were lower after the induction of anesthesia and at 20min following surgical incision (p<0.05). Awakening time was shorter in the esmolol group (p<0.001); Ramsay Sedation Scale scores at 10min after extubation were lower in the esmolol group (p<0.05). The modified Aldrete scores at all measurement time points during the recovery period were relatively lower in the lidocaine group (p<0.05). The time to attain a modified Aldrete score of ≥9 points was prolonged in the lidocaine group (p<0.01). Postoperative resting and dynamic VAS scores were higher in the lidocaine group at 10 and 20min after extubation (p<0.05, p<0.01, respectively). Analgesic supplements were less frequently required in the lidocaine group (p<0.01). In laparoscopic cholecystectomies, lidocaine infusion had superiorities over esmolol infusions regarding the suppression of responses to tracheal extubation and postoperative need for additional analgesic agents in the long run, while esmolol was more advantageous with respect to rapid recovery from anesthesia, attenuation of early postoperative pain, and modified Aldrete recovery (MAR) scores and time to reach MAR score of 9 points. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
Dogan, Serpil Dagdelen; Ustun, Faik Emre; Sener, Elif Bengi; Koksal, Ersin; Ustun, Yasemin Burcu; Kaya, Cengiz; Ozkan, Fatih
We compared the effects of lidocaine and esmolol infusions on intraoperative hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery in laparoscopic cholecystectomy surgery. The first group (n=30) received IV lidocaine infusions at a rate of 1.5mg/kg/min and the second group (n=30) received IV esmolol infusions at a rate of 1mg/kg/min. Hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery characteristics were evaluated. In the lidocaine group, systolic arterial blood pressures values were lower after the induction of anesthesia and at 20min following surgical incision (p<0.05). Awakening time was shorter in the esmolol group (p<0.001); Ramsay Sedation Scale scores at 10min after extubation were lower in the esmolol group (p<0.05). The modified Aldrete scores at all measurement time points during the recovery period were relatively lower in the lidocaine group (p<0.05). The time to attain a modified Aldrete score of ≥9 points was prolonged in the lidocaine group (p<0.01). Postoperative resting and dynamic VAS scores were higher in the lidocaine group at 10 and 20min after extubation (p<0.05, p<0.01, respectively). Analgesic supplements were less frequently required in the lidocaine group (p<0.01). In laparoscopic cholecystectomies, lidocaine infusion had superiorities over esmolol infusions regarding the suppression of responses to tracheal extubation and postoperative need for additional analgesic agents in the long run, while esmolol was more advantageous with respect to rapid recovery from anesthesia, attenuation of early postoperative pain, and modified Aldrete recovery (MAR) scores and time to reach MAR score of 9 points. Copyright © 2014. Publicado por Elsevier Editora Ltda.
Branthwaite, A; Cooper, P
The effect of branding--that is, the labelling and marketing--of a well-known proprietary analgesic used to treat headaches was studied in a sample of women given a branded or unbranded form with either an inert or an active formulation. The sample was also divided according to whether the subjects were regular users of the brand or users of other brands. The findings showed that branded tablets were overall significantly more effective than unbranded tablets in relieving headaches. Differential effects were observed: the effects of branding were more noticeable one hour after the tablets were taken compared with 30 minutes; in the women given the placebo; and in the users of the brand compared with the users of other brands. It is hypothesised that these effects are due to increased confidence in obtaining relief with a well-known brand, and that branding has an analgesic effect that interacts with the analgesic effects of placebos and active ingredients. PMID:6786566
Mwase, Richard; Kasumba, John Mark; Wanzira, Humphrey; Kintu, Andrew; Tindimwebwa, Joesph V. B.; Obua, Daniel
Background. Good postoperative analgesic management improves maternal satisfaction and care of the neonate. Postoperative pain management is a challenge in Mulago Hospital, yet ketamine is accessible and has proven benefit. We determined ketamine's postoperative analgesic effects. Materials and Methods. We did an RCT among consenting parturients that were randomized to receive either intravenous ketamine (0.25 mg/kg) or placebo after spinal anesthetic. Pain was assessed every 30 mins up to 24 hours postoperatively using the numerical rating scale. The first complaint of pain requiring treatment was noted as “time to first breakthrough pain.” Results. We screened 100 patients and recruited 88 that were randomized into two arms of 44 patients that received either ketamine or placebo. Ketamine group had 30-minute longer time to first breakthrough pain and lower 24-hour pain scores. Postoperative diclofenac consumption was lesser in the ketamine group compared to placebo and Kaplan-Meier graphs showed a higher probability of experiencing breakthrough pain earlier in the placebo group. Conclusion. Preincision intravenous ketamine (0.25 mg/kg) offered 30-minute prolongation to postoperative analgesia requirement with reduced 24-hour pain scores. We recommend larger studies to explore this benefit. This trial is registered with Pan African Clinical Trial Registry number PACTR201404000807178. PMID:28321251
Miller, Jane; Dunion, Amy; Dunn, Nina; Fitzmaurice, Carolyn; Gamboa, Margaret; Myers, Sarah; Novak, Paula; Poole, Jill; Rice, Kimberly; Riley, Caroline; Sandberg, Ruth; Taylor, Daniel; Gilmore, Lisa
The majority of massage therapy studies have evaluated 20- to 45-minute interventions in nonsurgical patients. Studies are needed to evaluate the effects of a brief massage intervention that would be more clinically feasible for bedside clinicians to administer as an adjunct to pharmacologic pain management in acutely ill surgical patients. To evaluate the impact of a brief massage intervention in conjunction with analgesic administration on pain, anxiety, and satisfaction with pain management in postoperative orthopaedic inpatients. A convenience sample of postoperative orthopaedic patients was studied during two therapeutic pain treatments with an oral analgesic medication. A pretest, posttest, randomized, controlled trial study design, with crossover of subjects, was used to evaluate the effect of a 5-minute hand and arm massage at the time of analgesic administration. Each patient received both treatments (analgesic administration alone [control]; analgesic administration with massage) during two sequential episodes of postoperative pain. Prior to administration of the analgesic medication, participants rated their level of pain and anxiety with valid and reliable tools. Immediately after analgesic administration, a study investigator provided the first, randomly assigned treatment. Pain and anxiety were rated by the participant 5 and 45 minutes after medication administration. Satisfaction with pain management was also rated at the 45-minute time point. Study procedures were repeated for the participant's next requirement for analgesic medication, with the participant receiving the other randomly assigned treatment. Analysis of variance was used to determine whether pain, anxiety, and/or satisfaction with pain management differed between the two treatment groups and/or if treatment order was a significant factor. The level of significance for all tests was set at p < .05. Twenty-five postoperative patients were studied during two sequential episodes of pain
Choi, Soo Joo; Kim, Myung Hee; Jeong, Hui Yeon; Lee, Jeong Jin
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.
Lemarie, M; Compère, V; Fourdrinier, V; Lignot, S; Legrand, L; Marguerite, C; Devellenne, C; Wood, G; Dujardin, F; Dureuil, B
Postoperative pain at home in ambulatory surgery is a major problem. To improve its management, the French society of anaesthesia emphasizes the importance of writing prescriptions for analgesic during the preanaesthetic consultation. The objective of this study was to assess the impact of this prescription on the incidence of postoperative pain at home in ambulatory orthopaedic surgery. We conducted a prospective evaluation in the ambulatory surgery unit of Rouen University Hospital. We were able to identify two periods of 1 year with implementation of a systematic prescription of analgesics during the postoperative period (P1) or during the preanaesthetic consultation (P2). The evaluation of this measurement was made by a telephone survey conducted the day after surgery. The main parameter was the incidence of postoperative pain at home defined by the occurrence of a pain greater to 3/10 on a numerical scale (FR). Secondary parameters were demographic and anaesthetic data, the incidence of moderate pain (FR ≤ 3), treatment adherence and patient satisfaction. We included 638 patients and 531 were analysed: 28% of patients had an EN greater than 3 the day following surgery. There is no difference between the two periods (30% for P1 versus 27% for P2). The analysis of subgroups showed that in the general anaesthesia group, 30% of patients had an EN greater than 3 for P1 versus 18% for P2 (P<0.01). Furthermore, 55% of patients expressed moderate pain (FR ≤ 3) for P1 versus 22% for P2 (P<0.01). Moreover, 89% of patients reported having an adequate analgesic treatment. The overall observance was 64%, 53% for P1 versus 75% for P2 (P<0.01). The systematic prescription of analgesics during the preanaesthetic consultation does not decrease the intensity of moderate to severe pain. On the other hand, this procedure seems to be positive for the people who underwent a general anaesthesia. Copyright © 2011 Elsevier Masson SAS. All rights reserved.
Günther, Thomas; Dasgupta, Pooja; Mann, Anika; Miess, Elke; Kliewer, Andrea; Fritzwanker, Sebastian; Steinborn, Ralph; Schulz, Stefan
Classical opioid analgesics, including morphine, mediate all of their desired and undesired effects by specific activation of the μ-opioid receptor (μ receptor). The use of morphine for treating chronic pain, however, is limited by the development of constipation, respiratory depression, tolerance and dependence. Analgesic effects can also be mediated through other members of the opioid receptor family such as the κ-opioid receptor (κ receptor), δ-opioid receptor (δ receptor) and the nociceptin/orphanin FQ peptide receptor (NOP receptor). Currently, a new generation of opioid analgesics is being developed that can simultaneously bind with high affinity to multiple opioid receptors. With this new action profile, it is hoped that additional analgesic effects and fewer side effects can be achieved. Recent research is mainly focused on the development of bifunctional μ/NOP receptor agonists, which has already led to novel lead structures such as the spiroindole-based cebranopadol and a compound class with a piperidin-4-yl-1,3-dihydroindol-2-one backbone (SR16835/AT-202 and SR14150/AT-200). In addition, the ornivol BU08028 is an analogue of the clinically well-established buprenorphine. Moreover, the morphinan-based nalfurafine exerts its effect with a dominant κ receptor-component and is therefore utilized in the treatment of pruritus. The very potent dihydroetorphine is a true multi-receptor opioid ligand in that it binds to μ, κ and δ receptor. The main focus of this review is to assess the paradigm of opioid ligands targeting multiple receptors with a single chemical entity. We reflect on this rationale by discussing the biological actions of selected multi-opioid receptor ligands, but not on their medicinal chemistry and design.
Hasani, Antigona; Soljakova, Marija; Jakupi, Muharrem; Ustalar-Ozgen, Serpil
The aim of the present study was to investigate the preemptive analgesic effects of intraperitoneally administrated midazolam and diclofenac, before acute and inflammatory induced pain in rat model. One hundred twenty-eight (n=8 in each group) male Sprague Dawley rats were included in the study. Paw movements in response to thermal stimulation or paw flinching in response to formalin injection were compared after midazolam (0.1, 1, 5 and 10 mg/kg) and diclofenac (10 mg/kg), intraperitoneal administration. Saline was used as a control. Preemptive analgesic effect was significant in both tests when diclofenac and midazolam was administrated before the pain stimuli (p<0.01 and p<0.001). Intraperitoneal injection of midazolam in doses 5 and 10 mg/kg, increase the response time in hot plate test and decrease the number of flinches in formalin test (p<0.01 vs. p<0.001). ED50 of midazolam (with diclofenac) in hot plate test was 2.02 mg/kg (CI95% =-3.47-5.03 mg); and, 0.9 mg/kg (CI95% =-0.87-4.09 mg) in phase I and 0.7 mg/kg (CI95% = 0.48-6.63 mg) in phase II, in formalin test. Intraperitoneally administered midazolam and diclofenac had preemptive analgesic effects on acute thermal, and inflammatory induced pain in rats. PMID:21619559
Polzin, Amin; Hohlfeld, Thomas; Kelm, Malte; Zeus, Tobias
Aspirin is the mainstay in prophylaxis of cardiovascular diseases. Impaired aspirin antiplatelet effects are associated with enhanced incidence of cardiovascular events. Comedication with non-opioid analgesic drugs has been described to interfere with aspirin, resulting in impaired aspirin antiplatelet effects. Additionally, non-opioid analgesic medication has been shown to enhance the risk of cardiovascular events and death. Pain is very frequent and many patients rely on analgesic drugs to control pain. Therefore effective analgesic options without increased risk of cardiovascular events are desirable. This review focuses on commonly used non-opioid analgesics, interactions with aspirin medication and impact on cardiovascular risk. PMID:26225198
Polzin, Amin; Hohlfeld, Thomas; Kelm, Malte; Zeus, Tobias
Aspirin is the mainstay in prophylaxis of cardiovascular diseases. Impaired aspirin antiplatelet effects are associated with enhanced incidence of cardiovascular events. Comedication with non-opioid analgesic drugs has been described to interfere with aspirin, resulting in impaired aspirin antiplatelet effects. Additionally, non-opioid analgesic medication has been shown to enhance the risk of cardiovascular events and death. Pain is very frequent and many patients rely on analgesic drugs to control pain. Therefore effective analgesic options without increased risk of cardiovascular events are desirable. This review focuses on commonly used non-opioid analgesics, interactions with aspirin medication and impact on cardiovascular risk.
Berna, C; Cojan, Y; Vuilleumier, P; Desmeules, J
Over the past twenty years, neuroscience has changed our understanding of placebo analgesia. Often perceived by researchers as a response bias adding noise to the assessment of efficacy, in the patients' view, it is associated with charlatanism. The origin of the word, qualifying a patient's response to "please" the doctor, did not help its rightful appreciation. However, today the placebo analgesia is considered as a psychobiological phenomenon. Thanks to pharmacological manipulations and the development of functional brain imaging, the neural circuitry involved in this effect as well as the role of endorphins and dopamine have been identified. This article describes our current knowledge about this fascinating phenomenon: a psychological modulation can lead to a biological effect.
Ezzat, Abdelrahman E M; El-Shenawy, Hanna M; El-Begermy, Marwa M; Eid, Mustafa I; Akel, Mabrouk M; Abbas, Ayman Y
The postoperative period after palatal surgery is usually very painful, requiring the use of pain-relieving drugs. Hence, the aim of this study was to evaluate the efficacy of Low-level laser therapy (LLLT) in post-operative pain control and edema after secondary palatal operations. A randomized double blinded clinical study on 20 children undergoing secondary palatal operations between 2013 and 2015 was done. Patients were randomly divided on two groups 10 patients each. In one group patients received local application of therapeutic laser immediately after surgery while patients received nothing in the control group. The mean age was 5.22 years ± 2.53 SD in the laser group and 6.42 years ± 0.76 in the control group. Postoperative pain was assessed by using visual analog scale scores and by recording the need of analgesics. The degree of postoperative edema was also recorded. The pain scale showed significantly less postoperative pain in the laser group than in the control group from the first day (P-value = 0.006) to the 6th day (P-value = 0.014). The number of postoperative analgesic doses needed were significantly less in the laser group in the second and third days (P-value = 0.014). The postoperative edema was significantly higher in the control group from the 2nd (P-value = 0.004) to the 7th (P-value = 0.014) postoperative days. Preliminary results showed that low-level laser therapy is effective in the reduction of postoperative pain and edema, and minimizing the need of analgesic medication after secondary palatal operations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Barney, Chantel C; Merbler, Alyssa M; Quest, Kelsey; Byiers, Breanne J; Wilcox, George L; Schwantes, Scott; Roiko, Samuel A; Feyma, Timothy; Beisang, Arthur; Symons, Frank J
Rett syndrome is associated with severe motor and communicative impairment making optimal postoperative pain management a challenge. There are case reports documenting reduced postoperative analgesic requirement in Rett syndrome. The goal of this preliminary investigation was to compare postoperative analgesic management among a sample of girls with Rett syndrome compared to girls with and without developmental disability undergoing spinal fusion surgery. The medical records of eight girls with Rett syndrome (mean age = 13.2 years, sd = 1.9), eight girls with developmental disability (cerebral palsy; mean age = 13.1 years, sd = 2.0), and eight girls without developmental disability (adolescent idiopathic scoliosis; mean age = 13.4, sd = 1.8) were reviewed. Data related to demographics, medications, and route of drug administration were recorded. Girls with Rett syndrome received significantly fewer morphine equivalent opioids postoperatively (M = 0.26 mg·kg(-1) ·day(-1) , sd = 0.10) compared to girls with adolescent idiopathic scoliosis (M = 0.47mg·kg(-1) ·day(-1) , sd = 0.13; 95% CI -0.34 to -0.08; P = 0.001) and girls with CP (M = 0.40 mg·kg(-1) per day, sd = 0.14; 95% CI -0.27 to -0.02; P = 0.01). Girls with Rett syndrome received significantly fewer opioid patient-controlled analgesic (PCA) bolus doses (given by proxy; M = 42.63, sd = 17.84) compared to girls with adolescent idiopathic scoliosis (M = 98.25, sd = 52.77; 95% CI -96.42 to -14.83; P = 0.01). There was also some evidence indicating girls with Rett syndrome received fewer bolus doses compared to girls with CP (M = 80.88, sd = 38.93; 95% CI -79.05 to 2.55; P = 0.06). On average, girls with Rett syndrome also received smaller total doses of acetaminophen, diazepam, and hydroxyzine. This study highlights possible discrepancies in postoperative pain management specific to girls with Rett syndrome and suggests further investigation is warranted to determine best practice for postoperative analgesic
Acharya, Sahana Devadasa; Ullal, Sheetal Dinkar; Padiyar, Shivaraj; Rao, Yalla Durga; Upadhyaya, Kousthubha; Pillai, Durga; Raj, Vishnu
To evaluate the analgesic effect of extracts of Alpinia galanga (AG) rhizome in mice and elucidate the possible mechanism for its analgesic action. Analgesic action of extracts of AG rhizome was studied in three experimental models of nociception. Albino mice of both sexes weighing 25 to 30 g were used in this study. For the hot-plate test, mice in the five groups with six in each received three different doses of ethanolic extracts of dried rhizome of AG suspended in 2% gum acacia orally, morphine subcutaneously and 2% gum acacia orally, respectively. Reaction time was observed after administration of vehicle or drugs. For the hot-plate test after naloxone pretreatment, mice in the five groups received naloxone subcutaneously 30 min prior to the administration of vehicle or drugs and reaction time was observed as explained above. In the writhing test, writhes were induced by injecting acetic acid intraperitoneally in another 30 mice which were randomly allocated to five groups of six in each and received three different doses of ethanolic extracts of dried rhizome of AG suspended in 2% gum acacia, aspirin suspended in 2% gum acacia and 2% gum acacia orally, respectively. The mice were observed individually for a period of 15 min and the number of writhes was recorded for each animal. AG treatment significantly increased the latency period in the hot-plate test at all three doses at 30, 60, 90 and 120 min time intervals compared with control group (P<0.05 or P<0.01). Naloxone pretreatment significantly reduced the latency period in hot-plate test for both AG and morphine groups as compared with corresponding groups that did not receive naloxone pretreatment (P<0.05 or P<0.01). AG at all doses significantly reduced the number of writhes compared with control group (P<0.01). The study confirmed the analgesic effect of AG rhizome and hence justified its use in ethnomedicine for the treatment of pain due to various causes. The probable mechanism of its analgesic action
Background: Experimental models using short-duration noxious stimuli have led to the concept of preemptive analgesia. Ketorolac, a nonsteroidal anti-inflammatory drug, has been shown to have a postoperative narcotic-sparing effect when given preoperatively and alternatively to not have this effect. This study was undertaken to determine whether a single intravenous (IV) dose of ketorolac would result in decreased postoperative pain and narcotic requirements. Methods: In a double-blind, randomized controlled trial, 48 women undergoing abdominal hysterectomy were studied. Patients in the ketorolac group received 30 mg of IV ketorolac 30 min before surgical incision, while the control group received normal saline. The postoperative analgesia was performed with a continuous infusion of tramadol at 12 mg/h with the possibility of a 10 mg bolus for every 10 min. Pain was assessed using the visual analog scale (VAS), tramadol consumption, and hemodynamic parameters at 0, 1, 2, 4, 8, 12, 16, and 24 h postoperatively. We quantified times to rescue analgesic (morphine), adverse effects, and patient satisfaction. Results: There were neither significant differences in VAS scores between groups (P > 0.05) nor in the cumulative or incremental consumption of tramadol at any time point (P > 0.05). The time to first requested rescue analgesia was 66.25 ± 38.61 min in the ketorolac group and 65 ± 28.86 min in the control group (P = 0.765). There were no significant differences in systolic blood pressure (BP) between both groups, except at 2 h (P = 0.02) and 4 h (P = 0.045). There were no significant differences in diastolic BP between both groups, except at 4 h (P = 0.013). The respiratory rate showed no differences between groups, except at 8 h (P = 0.017), 16 h (P = 0.011), and 24 h (P = 0.049). These differences were not clinically significant. There were no statistically significant differences between groups in heart rate (P > 0.05). Conclusions: Preoperative ketorolac
Haraji, A; Rakhshan, V
Reports on post-surgical pain are a few, controversial and flawed (by statistics and analgesic consumption). Besides, it is not known if chlorhexidine can reduce post-extraction pain adjusting for its effect on prevention of infection and dry socket (DS). We assessed these. A total of 90 impacted mandibular third molars of 45 patients were extracted. Intra-alveolar 0·2% chlorhexidine gel was applied in a split-mouth randomised design to one-half of the sockets. None of the included patients took antibiotics or analgesics afterwards. In the first and third post-operative days, DS formation and pain levels were recorded. Predictive roles of the risk factors were analysed using fixed-effects (classic) and multilevel (mixed-model) multiple linear regressions (α = 0·05, β≤0·1). In the first day, pain levels were 5·56 ± 1·53 and 4·78 ± 1·43 (out of 10), respectively. These reduced to 3·22 ± 1·41 and 2·16 ± 1·40. Pain was more intense on the control sides [both P values = 0·000 (paired t-test)]. Chlorhexidine had a significant pain-alleviating effect (P = 0·0001), excluding its effect on DS and infection. More difficult surgeries (P = 0·0201) and dry sockets were more painful (P = 0·0000). Age had a marginally significant negative role (P = 0·0994). Gender and smoking had no significant impact [P ≥ 0·7 (regression)]. The pattern of pain reduction differed between dry sockets and healthy sockets [P = 0·0102 (anova)]. Chlorhexidine can reduce pain, regardless of its infection-/DS-preventive effects. Simpler surgeries and sockets not affected by alveolar osteitis are less painful. Smoking and gender less likely affect pain. The role of age was not conclusive and needs future studies.
Radwan, Mahasen A; Abou El Ela, Amal El Sayeh F; Hassan, Maha A; El-Maraghy, Dalia A
The efficacy of ketorolac tromethamine (KT) floating alginate beads as a drug delivery system for better control of KT release was investigated. The formulation with the highest drug loading, entrapment efficiency, swelling, buoyancy, and in vitro release would be selected for further in vivo analgesic effect in the mice and pharmacokinetics study in rats compared to the tablet dosage form. KT floating alginate beads were prepared by extrusion congealing technique. KT in plasma samples was analyzed using a UPLC MS/MS assay. The percentage yield, drug loading and encapsulation efficiency were increased proportionally with the hydroxypropylmethyl cellulose (HPMC) polymer amount in the KT floating beads. A reverse relationship was observed between HPMC amount in the beads and the KT in vitro release rate. F3-floating beads were selected, due to its better in vitro results (continued floating for >8 h) than others. A longer analgesic effect was observed for F3 in fed mice as compared to the tablets. After F3 administration to rats, the Cmax (2.2 ± 0.3 µg/ml) was achieved at ∼2 h and the decline in KT concentration was slower. F3 showed a significant increase in the AUC (1.89 fold) in rats as compared to the tablets. KT was successfully formulated as floating beads with prolonged in vitro release extended to a better in vivo characteristic with higher bioavailability in rats. KT in floating beads shows a superior analgesic effect over tablets, especially in fed mice.
Menéndez, Luis; Lastra, Ana; Meana, Alvaro; Hidalgo, Agustín; Baamonde, Ana
The intratibial inoculation of NCTC 2472 cells induces an osteosarcoma in C3H/HeJ mice. These mice show thermal hyperalgesic responses which may be blocked by the local administration of opiates over the tibial tumoral mass (Menéndez L, Lastra A, Hidalgo A, Meana A, Garcia E, Baamonde A. Peripheral opioids act as analgesics in bone cancer pain in mice. NeuroReport 2003b; 14:867-9). The aim of this report was to characterize the analgesic responses obtained by activating peripheral opioid receptors in bone cancer pain. Here, we initially describe that this osteosarcoma induces mechanical as well as thermal hyperalgesia. Loperamide, an opioid agonist unable to cross the blood-brain barrier, inhibits both thermal and mechanical hyperalgesia when s.c. injected, locally over the tibial tumoral mass (7.5-75 microg) or distantly, under the fur of the neck (4 mg/kg). These analgesic effects seem peripherally mediated since they are reverted by the administration of naloxone methiodide (10 mg/kg) and because the withdrawal latencies of the contralateral, non-affected, paws remain unaltered. Furthermore, only cyprodime (1 mg/kg) but not naltrindole (0.1 mg/kg) or nor-binaltorphimine (10 mg/kg) blocked these effects, showing the involvement of gamma-opioid receptors in the peripheral analgesia induced by loperamide on thermal and mechanical hyperalgesia. The advantages of using peripheral acting opiates -- devoid of central colateral effects -- for the treatment of cancer related pain are suggested.
Esparza-Villalpando, Vicente; Chavarria-Bolaños, Daniel; Gordillo-Moscoso, Antonio; Masuoka-Ito, David; Martinez-Rider, Ricardo; Isiordia-Espinoza, Mario; Pozos-Guillen, Amaury
The aim of this study was to compare the efficacy of preoperative and postoperative dexketoprofen trometamol for pain control after third molar surgery. Sixty subjects indicated for impacted mandibular third molar surgery were randomly assigned to two groups: preoperative (group 1, n = 30) and postoperative (group 2, n = 30) administration. Group 1 received 25 mg of dexketoprofen trometamol 30 min before surgery and 1 placebo capsule (same color and size with active drug) immediately after surgery. Group 2 received the placebo capsule 30 min before surgery and 25 mg of dexketoprofen trometamol immediately after surgery. Pain intensity was assessed using a numeric rating scale (NRS) during the first 8 h. The time of the need for a second dose of dexketoprofen trometamol, after the first administration, was recorded. The data were analyzed using mixed-model repeated-measures (MMRM), Wilcoxon rank-sum, and Kaplan-Meier analysis. After the 8 h period, no statistically significant difference was observed in the intensity of pain (MMRM, p = 0.41); and no significant difference in the time for a second dose (p = 0.956). In conclusion, preoperative administration of dexketoprofen trometamol is a reasonable clinical approach that is as effective as conventional postoperative pharmacological treatment, with the advantage of allowing early analgesia before pain develops. (ClinicalTrials.gov: NCT02380001).
Anesthesia; General Anesthesia; Analgesics, Opioid; Postoperative Complications; Pathologic Processes; Physiologic Effects of Drugs; Narcotics; Analgesics; Sleep Disordered Breathing; Obstructive Sleep Apnea of Child; Tonsillectomy; Respiratory Depression; Dexmedetomidine; Ketamine; Lidocaine; Gabapentin; Pulse Oximetry
Ucuzal, Meral; Kanan, Nevin
The aim of this study was to determine the effect of foot massage on pain after breast surgery, and provide guidance for nurses in nonpharmacologic interventions for pain relief. This was a quasiexperimental study with a total of 70 patients who had undergone breast surgery (35 in the experimental group and 35 in the control group). Patients in the control group received only analgesic treatment, whereas those in the experimental group received foot massage in addition to analgesic treatment. Patients received the first dose of analgesics during surgery. As soon as patients came from the operating room, they were evaluated for pain severity. Patients whose pain severity scored ≥4 according to the Short-Form McGill Pain Questionnaire were accepted into the study. In the experimental group, pain and vital signs (arterial blood pressure, pulse, and respiration) were evaluated before foot massage at the time patients complained about pain (time 0) and then 5, 30, 60, 90, and 120 minutes after foot massage. In the control group, pain and vital signs were also evaluated when the patients complained about pain (time 0) and again at 5, 30, 60, 90, and 120 minutes, in sync with the times when foot massage was completed in the experimental group. A patient information form was used to collect descriptive characteristics data of the patients, and the Short-Form McGill Pain Questionnaire was used to determine pain severity. Data were analyzed for frequencies, mean, standard deviation, chi-square, Student t, Pillai trace, and Bonferroni test. The results of the statistical analyses showed that patients in the experimental group experienced significantly less pain (p ≤ .001). Especially notable, patients in the experimental group showed a decrease in all vital signs 5 minutes after foot massage, but patients in the control group showed increases in vital signs except for heart rate at 5 minutes. The data obtained showed that foot massage in breast surgery patients was
da Costa Araújo, Fábio Andrey; de Santana Santos, Thiago; de Morais, Hécio Henrique Araújo; Laureano Filho, José Rodrigues; de Oliveira E Silva, Emanuel Dias; Vasconcellos, Ricardo José Holanda
The aim of this prospective, randomized, controlled, paired trial was to perform a comparative analysis of the preemptive analgesic effect of nimesulide and tramadol chlorhydrate during third molar surgery. The study was carried out between March and November 2009, involving 94 operations in 47 male and female patients with bilateral impacted lower third molars in comparable positions. The sample was divided into two groups. Group A received an oral dose of 100 mg of nimesulide 1 h prior to surgery. Group B received an oral dose of 100 mg of tramadol chlorhydrate 1 h prior to surgery. The following aspects were evaluated in the postoperative period: adverse effects of the drugs; amount of rescue medication used (acetaminophen 750 mg); and pain 5, 6, 24, 36, 48, 60, 72 and 84 h after surgery using a visual analog pain scale. Peak pain occurred 5 h after surgery in both groups, with a mean pain score of 2.3 in Group A and 3.0 in Group B; this difference did not achieve statistical significance (p > 0.141). Based on the sample studied, nimesulide and tramadol chlorhydrate demonstrate similar preemptive analgesic effects when used in lower third molar surgeries.
Heidari, S Morteza; Mirlohi, S Zahra; Hashemi, S Jalal
There is a little data about rectal administration of Ketamine as a postoperative analgesic, so we compared the efficacy of rectal ketamine with rectal acetaminophen, which is applied routinely for analgesia after painful surgeries like tonsillectomy. In this single-blinded comparative trial, we enrolled 70 children undergoing elective tonsillectomy, and divided them randomly in two groups. Patients received rectal ketamine (2 mg / kg) or rectal acetaminophen (20 mg / kg) at the end of surgery. The children's Hospital of Eastern Ontario Pain scale was used to estimate pain in children. Also the vital signs, Wilson sedation scale, and side effects in each group were noted and compared for 24 hours. The ketamine group had a lower pain score at 15 minutes and 60 minutes after surgery in Recovery (6.4 ± 0.8, 7.4 ± 1 vs. 7.1 ± 1.2, 7.8 ± 1.2 in the acetaminophen group, P < 0.05) and one hour and two hours in the ward (7.2 ± 0.7, 7 ± 0.5 vs. 7.9 ± 1.2, 7.5 ± 1.2 in the acetaminophen group, P < 0.05), with no significant differences till 24 hours. Dreams and hallucinations were not reported in the ketamine group. Systolic blood pressure was seen to be higher in the ketamine group (104.4 ± 7.9 vs. 99.8 ± 7.7 in the acetaminophen group) and nystagmus was reported only in the ketamine group (14.2%). Other side effects were equivalent in both the groups. With low complications, rectal ketamine has analgesic effects, especially in the first hours after surgery in comparison with acetaminophen, and it can be an alternative analgesic with easy administration in children after tonsillectomy.
Postoperative pain control by preventive intercostal nerve block under direct vision followed by catheter-based infusion of local analgesics in rib cartilage harvest for auricular reconstruction in children with microtia: A randomized controlled trial.
Woo, Kyong-Je; Kang, Bo Young; Min, Jeong Jin; Park, Jin-Woo; Kim, Ara; Oh, Kap Sung
Children with microtia complain of severe postoperative pain during early postoperative days after rib cartilage harvest for auricular reconstruction. The purpose of this study was to evaluate the effects of preventive donor site wound analgesia by intercostal nerve block (ICNB) and catheter-based infusion of local analgesics on postoperative pain after rib cartilage graft for auricular reconstruction in children with microtia. In this prospective randomized study, 66 children underwent postoperative pain control using either preventive ICNB followed by catheter-based infusion (33 patients, study group) or intravenous (IV) analgesia alone (33 patients, control group). ICNB was performed under direct vision by the surgeon by injecting 0.5% bupivacaine into each of the three intercostal spaces before perichondrial dissection. Catheters were placed in three subchondral spaces before wound closure, and 0.5% bupivacaine was infused every 12 h for 48 h postoperatively. Pain degrees were recorded every 4 h during the first 48 postoperative hours using a visual analogue scale. The study group showed significantly lower mean pain scores of the chest at rest (3.7 vs. 5.1, p = 0.001), the chest during coughing (4.3 vs. 5.8, p = 0.006), and the ear (3.0 vs. 4.1, p = 0.001) than the control group. The amount of use of rescue IV ketorolac was smaller in the study group (p = 0.026) than in the control group. No side effects related to the intervention were noted. Preventive ICNB followed by catheter-based infusion is effective and safe in postoperative pain relief in rib cartilage graft for auricular reconstruction. (The clinical trial registration number: WHO ICTRP, apps.who.int/trialsearch (KCT0001668)). Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Kalani, Navid; Sanie, Mohammad Sadegh; Zabetian, Hasan; Radmehr, Mohammad; Sahraei, Reza; Kargar Jahromi, Hossein; Zare Marzouni, Hadi
BACKGROUND New drugs are increasingly used to induce analgesia during surgeries. This study compared the analgesic effects of paracetamol and magnesium sulfate. METHODS Sixty patients with American Society of Anesthesiologists (ASA) class I or II patients who were candidates for surgery of the lower limbs were randomly divided into three equal groups who were age and gender matched. Group 1 received paracetamol, and group 2, the magnesium sulfate during surgery and group 3 as the control. Pain intensities were measured and recorded using the Visual Analog Scale before surgery, in the recovery room, and 6, 12, and 18 hours after surgery. RESULTS Pain intensities (7.10, 5.80, and 4.10) were higher in the control group; 6, 12, and 18 hours after surgery compared to the paracetamol (6.45, 4.15, 2.50) and the magnesium groups (7.25, 4.55, and 2.05), but the difference was not statistically significant. CONCLUSION Paracetamol and magnesium sulfate were shown to have postoperative analgesic effects and reduce the quantity of narcotic use after surgery. PMID:27853692
Molsberger, A; Hille, E
The immediate analgesic effect of a single non-segmental acupuncture stimulation treatment on chronic tennis elbow pain was studied in a placebo-controlled single-blind trial completed by 48 patients. Before and after treatment, all patients were examined physically by an unbiased independent examiner. Eleven-point box scales were used  for pain measurement. Patients in the verum group were treated at non-segmental distal points (homolateral leg) for elbow pain following Chinese acupuncture rules, whereas patients in the placebo group were treated with placebo acupuncture avoiding penetration of the skin with an acupuncture needle. Overall reduction in the pain score was 55.8% (S = 2.95) in the verum group and 15% (S = 2.77) in the placebo group. After one treatment 19 out of 24 patients in the verum group (79.2%) reported pain relief of at least 50% (placebo group: six patients out of 24). The average duration of analgesia after one treatment was 20.2 h in the verum group (S = 21.54) and 1.4 h (S = 3.50) in the placebo group. The results are statistically significant (P < 0.01); they show that non-segmental verum acupuncture has an intrinsic analgesic effect in the clinical treatment of tennis elbow pain which exceeds that of placebo acupuncture.
Bromm, B; Herrmann, W M; Scharein, E
In the present study involving healthy test subjects, tilidin/naloxone (Valoron N; VAL) proved to have an analgesic effect roughly twice as pronounced as that of tramadol (TRA). Moreover, the analgesic effect of VAL showed a significantly more rapid onset than did that of TRA. This finding reflects the difference in rate of action of the active substances. In accordance with these findings, VAL is thus the most powerful analgesic presently available on the German market on simple prescription.
De Angelis, Federica; Tata, Ada Maria
Chronic pain represents a research field on great clinical relevance and social impactful. It is associated to a variety of pathological events causing un altered excitability of peripheral nerves derived by tissue damage depending on physical, biological and chemical injury. In the last years much attention has been paid in the identification of novel molecules involved in mediating pain sensation useful as therapeutic tools for the development of new analgesic drugs. Muscarinic receptors are widely distributed both in the central and peripheral nervous system. It is known that muscarinic agonists cause analgesic effects via spinal and supraspinal mechanisms. Considering that the analgesia induced by cholinergic agonists is comparable to that observed with morphine, the identification of receptor subtypes involved and the identification of the muscarinic ligands capable of selectively activate these receptors, is of considerable interest for potential therapeutic application. In the present review we describe the role of muscarinic receptors in mediating central and peripheral pain and the mechanisms downstream these receptors responsible of the modulation of nociceptive stimuli. Moreover the therapeutic perspectives and the identification of potential drugs binding muscarinic receptors involved in pain modulation will also be discussed.
Kaur, Sarvjeet; Saroa, Richa; Aggarwal, Shobha
Background: Use of opioids for perioperative analgesia is associated with sedation, respiratory depression and postoperative nausea and vomiting. N-methyl-D-aspartate receptor antagonist such as ketamine has both analgesic and antihyperalgesic properties. We studied the effect of intraoperative infusion of low-dose ketamine on postoperative analgesia and its management with opioids. Materials and Methods: A total of 80 patients scheduled for open cholecystectomy under general anesthesia were randomly allocated into two equal groups in a randomized double-blinded way. The general anesthetic technique was standardized in both groups. Group K patients (n = 40) received bolus of ketamine 0.2 mg/kg intravenously followed by an infusion of 0.1 mg/kg/h before skin incision, which was continued up to the end of surgery. Similar volume of saline was infused in Group C (n = 40). The pain score at different intervals and cumulative morphine consumption over 24 h was observed. Secondary outcomes such as hemodynamic parameters, patient satisfaction score and incidences of side effects were also recorded. Results: Intraoperative infusion of low-dose ketamine resulted in effective analgesia in first 6 h of the postoperative period, which was evident from reduced pain scores and reduced opioid requirements (P = 0.001). The incidence of side effects and patient satisfaction were similar in both groups. Conclusion: Intraoperative low-dose ketamine infusion provides good postoperative analgesia while reducing need of opioid analgesics, which must be considered for better management of postoperative analgesia. PMID:26283834
Alipour, Mohammad; Tabari, Masoomeh; Faz, Reza Farhadi; Makhmalbaf, Hadi; Salehi, Maryam; Moosavitekye, Seyed Mostafa
Various drugs are administered intra-articularly to provide postoperative analgesia after arthroscopic knee surgery. The purpose of this study was to assess the analgesic effects of intra-articular injection of a dexmedetomidine following knee arthroscopy. Forty six patients scheduled for arthroscopic knee surgery under general anaesthesia, were randomly devided into two groups. Intervention group received 1µg/kg dexmedetomidine (D) and isotonic saline. Control group received 25ml isotonic saline (P). Analgesic effects were evaluated by measuring pain intensity (VAS scores) and duration of analgesia. There was no significant difference between the two groups in terms of age, sex and weight. The mean of post-operation pain severity in 1, 3, 6,12, and 24 h was significantly lower in the intervention group (D) in comparison with the control group (P). the mean of the total dose of tramadol consumption was significantly lower in the intervention group in comparison with the control group (P<0.001). Intra-articular injection of dexmedetomidine at the end of arthroscopic knee surgery, alleviates the patients' pain, reducing the postoperative need for narcotics as analgesics, and increase the first analgesic request after operation.
Alipour, Mohammad; Tabari, Masoomeh; faz, Reza Farhadi; Makhmalbaf, Hadi; Salehi, Maryam; Moosavitekye, Seyed Mostafa
Background: Various drugs are administered intra-articularly to provide postoperative analgesia after arthroscopic knee surgery. The purpose of this study was to assess the analgesic effects of intra-articular injection of a dexmedetomidine following knee arthroscopy. Methods: Forty six patients scheduled for arthroscopic knee surgery under general anaesthesia, were randomly devided into two groups. Intervention group received 1µg/kg dexmedetomidine (D) and isotonic saline. Control group received 25ml isotonic saline (P). Analgesic effects were evaluated by measuring pain intensity (VAS scores) and duration of analgesia. Results: There was no significant difference between the two groups in terms of age, sex and weight. The mean of post-operation pain severity in 1, 3, 6,12, and 24 h was significantly lower in the intervention group (D) in comparison with the control group (P). the mean of the total dose of tramadol consumption was significantly lower in the intervention group in comparison with the control group (P<0.001). Conclusions: Intra-articular injection of dexmedetomidine at the end of arthroscopic knee surgery, alleviates the patients’ pain, reducing the postoperative need for narcotics as analgesics, and increase the first analgesic request after operation. PMID:25207314
de Tovar, Clément; von Baeyer, Carl L; Wood, Chantal; Alibeu, Jean-Pierre; Houfani, Malik; Arvieux, Charles
To augment available validation data for the Faces Pain Scale - Revised (FPS-R) and to assess interscale agreement and preference in comparison with the Coloured Analogue Scale (CAS) in pediatric acute pain. The present prospective, multicentre study included 131 inpatients five to 15 years of age (mean age 8.8 years; 56% male) seen in postoperative recovery. They provided CAS and FPS-R pain scores before and after administration of analgesic medication. Nurses and physicians used the same tools as observational scales. Children and health care providers indicated which scale they preferred. FPS-R scores for the intensity of postoperative pain correlated highly with the corresponding CAS scores in all age groups (0.66
Choi, Soo Joo; Jeong, Hui Yeon; Lee, Jeong Jin
Background 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. Methods 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. Results 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. Conclusions 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. PMID:22679539
Good, M; Chin, C C
Music is a method nurses can use to help relieve pain, however little is known about its effectiveness across cultures. In this study, Western music was tested for its effectiveness in reducing postoperative pain in 38 Taiwanese patients, and its acceptability was explored. A pretest and post-test experimental design was used with visual analogue scales to measure sensation and distress of pain. Before surgery, subjects were randomly assigned to receive tape recorded music or the usual care. Those who were assigned to the music group chose among 5 types of sedative music. On postoperative Day 1 and Day 2, the effectiveness of the tape-recorded music was investigated during 15 minutes of rest in bed. Patients were interviewed on Day 3 to determine their liking for the music, its calming effects, and the helpfulness of the music. Repeated measures analysis of variance showed a significant interaction between time and group in the distress of pain on Day 1, but not on Day 2, and in pain sensation on Day 2, but not Day 1. Subjects from Taiwan were similar to subjects in a previous study in the United States in their liking for the music, and in reports of the helpfulness of the music for pain sensation and distress, but fewer Taiwanese found the music calming, and they had different choices: more chose harp music and fewer chose jazz than subjects in the U.S. study, and some would prefer Buddhist hymns or popular songs heard in Taiwan. Findings support the use of culturally acceptable music in addition to analgesic medication for the sensation and distress of postoperative pain.
Ittichaikulthol, Wichai; Prachanpanich, Naruemol; Kositchaiwat, Chutima; Intapan, Theerayut
Nonsteroidal antiinflammatory drugs (NSAIDs) in combination with opioids is a model of multimodal analgesia. NSAIDs have the oral and parenteral forms. The aim of the present study was to evaluate the efficacy of celecoxib compared with placebo and parecoxib after total hip or knee arthroplasty. A total of 120, ASA 1-2, aged 18-75 years, patients were randomly assigned to receive one of the three groups: Group I (control) received placebo (n=40), group II received 400 mg celecoxib orally (n=40) and group III received 40 mg parecoxib intravenously (n=40). The present study medication was administered I hour before surgery. All patients had access to patient-controlled analgesia (PCA) with intravenous morphine. Patients were studied at 0, 1, 6, 12 and 24 hours postoperatively for verbal numerical rating scale (VNRS), morphine consumption, satisfaction score and side effects. The intraoperatively fentayl requirement were similar among the three groups (p < 0.00). Celecoxib and parecoxib significantly decreased the amount of morphine requirement after total hip or knee arthroplasty compared to placebo at 1, 6, 12 and 24 hours (p < 0.00). The celecoxib group required more morphine than the parecoxib group at 1, 6, 12 and 24 hours (p < 0.00). The VNRS score in parecoxib group was significantly lower than the celecoxib and control groups at 1, 6, 12 but not at 24 hours. The VNRS score was lower in the celecoxib group compared to the control group at I and 6 hours postoperatively (p = 0.01, p < 0. 01 respectively). The placebo group had a higher sedation score (p = 0.008) but not for nausea vomiting (p = 0.36) and pruritus (p = 0.12) compared to the treatment groups. Within 12 hours after total hip and knee arthroplasty, pre-operative administration of parenteral parecoxib 40 mg was more effective than oral celecoxib 400 mg and placebo in terms of morphine consumption and VNRS score.
Dorman, T; Clarkson, K; Rosenfeld, B A; Shanholtz, C; Lipsett, P A; Breslow, M J
Surgical trauma results in diffuse sympathoadrenal activation which is thought to contribute to perioperative cardiovascular complications in high-risk patients. Regional anesthetic and analgesic techniques can attenuate this "stress response" and reduce the occurrence rate of adverse perioperative events; however, their use in the postoperative period is logistically difficult and costly. The present study was undertaken to evaluate whether transdermal administration of the alpha2 adrenergic-receptor agonist, clonidine, can be used as a pharmacologic means of blunting the stress response throughout the perioperative period. Double-blind, placebo-controlled clinical trial in patients undergoing pancreatico-biliary surgery. Operating rooms and surgical intensive care unit of a major university teaching hospital. Forty patients scheduled for major upper abdominal surgery. Patients received either clonidine (0.2 mg orally and a clonidine TTS-3 patch the evening before surgery and 0.3 mg orally on call to the operating room) or matched oral and transdermal placebo. Heart rate, systemic arterial blood pressure, plasma catecholamine, clonidine, interleukin-6 concentrations, and 24-hr urine cortisol and nitrogen excretion were measured the day before surgery and daily thereafter for 72 hrs postoperatively. Preoperative transdermal (and oral) clonidine administration resulted in therapeutic plasma clonidine concentrations throughout the perioperative period (1.54 +/- .07 [SEM] microg/mL). Clonidine reduced preoperative epinephrine and norepinephrine concentrations by 65%. Plasma catecholamine concentrations increased in both groups following surgery but were markedly lower throughout the postoperative period in patients receiving clonidine. Patients receiving clonidine had a reduced frequency rate of postoperative hypertension. Clonidine had no effect on plasma interleukin-6 concentration, urine cortisol excretion, or urine nitrogen excretion. No adverse effects of
Kim, So Yeon; Kim, Nam Kyu; Baik, Seung Hyuk; Min, Byung Soh; Hur, Hyuk; Lee, Jinae; Noh, Hyun-Young; Lee, Jong Ho; Koo, Bon-Neyo
There has been a rising interest in the possible association between perioperative opioid use and postoperative outcomes in cancer patients. Continuous surgical wound infiltration with local anesthetics is a nonopioid analgesic technique that can be used as a postoperative pain management alternative to opioid-based intravenous patient-controlled analgesia (IV PCA). The aim of this study was to compare the effects of an opioid-based analgesic regimen versus a local anesthetic wound infiltration-based analgesic regimen on immune modulation and short-term cancer recurrence or metastasis in patients undergoing laparoscopic resection of colorectal cancer.Sixty patients undergoing laparoscopic resection of colorectal cancer were randomly assigned to either the opioid group or the ON-Q group. For postoperative analgesia during the first 48 hours, the opioid group (n = 30) received fentanyl via IV PCA, whereas the ON-Q group (n = 30) received continuous wound infiltration of 0.5% ropivacaine with an ON-Q pump and tramadol via IV PCA. Pethidine for the opioid group and ketorolac or propacetamol for the ON-Q group were used as rescue analgesics. Anesthesia was induced and maintained with propofol and remifentanil. The primary outcome was postoperative immune function assessed by natural killer cell cytotoxicity (NKCC) and interleukin-2. Secondary outcomes were postoperative complications, cancer recurrence, or metastasis within 1 year after surgery, and postoperative inflammatory responses measured by white blood cell count, neutrophil percentage, and C-reactive protein. Immune function and inflammatory responses were measured before surgery and 24 and 48 hours after surgery.Fifty-nine patients completed the study. In the circumstance of similar pain control efficacy between the opioid group and the ON-Q group, postoperative NKCC and interleukin-2 levels did not differ between the 2 groups. The incidence of postoperative complications and recurrence or
Walker, Kristen A; Horning, Markus; Mellish, Jo-Ann E; Weary, Daniel M
This study examined the effects of two non-steroidal anti-inflammatory drug (NSAID) treatment protocols on the behavioral responses of juvenile Steller sea lions after abdominal surgery. Sea lions were randomly assigned to one of two treatments designed to control post-operative pain. The flunixin group (n=6) received flunixin meglumine (1mg/kg) administered as a single intramuscular (IM) injection before extubation from surgery. The carprofen group (n=5) received carprofen (4.4 mg/kg) as an IM injection before extubation, then orally at 24, 48 and 72 h after surgery. Seven behaviors related to post-operative pain were monitored by observers, blinded to treatment, for a total of 10 days (3 days pre-, day of surgery, and 6 days post-surgery). All seven behaviors changed after surgery regardless of NSAID treatment, two of which returned to baseline within 6 days of surgery. Only one behavior was mildly affected by analgesic treatment: sea lions in the carprofen group tended to spend less time lying down in Days 1-3 following surgery (i.e., the days which they received oral carprofen). These results suggested that neither treatment, at the dose administered, was effective in controlling pain in the days following this surgery.
Hu, Xiao-Jia; Jin, Hui-Zi; Xu, Wen-Zheng; Chen, Ming; Liu, Xiao-Hua; Zhang, Wei; Su, Juan; Zhang, Chuan; Zhang, Wei-Dong
The barks and roots of Edgeworthia chrysantha LINDL., which have been used as the folk medicine "Zhu shima" in southern China due to their detumescence and acesodyne effects, were investigated for their anti-inflammatory and analgesic activities using a xylene-induced ear edema assay in mice and Freund's complete adjuvant-induced paw edema as inflammation models, and the acetic acid-induced writhing test as an analgesic model. Fractions effective in terms of anti-inflammatory and analgesic activities were obtained from E. chrysantha. The chloroform-soluble fraction (CHF) showed significant anti-inflammatory (p<0.01-0.001) and analgesic (p<0.01) effects. On further purification by silica gel, three major coumarins, edgeworin (EdN), edgeworosides A and C (EdeA and EdeC), were isolated from the chloroform fraction and both anti-inflammatory and analgesic activities were evaluated. EdN and EdeA had anti-inflammatory (p<0.05-0.01) and analgesic (p<0.001) effects, while EdeC only showed an analgesic effect. The results of this study thus demonstrated that the coumarins EdN, EdeA and EdeC in this plant may be active constituents that contribute to the anti-inflammatory and analgesic effects.
Saraçoğlu, Ayten; Eti, Zeynep; Konya, Deniz; Kabahasanoğlu, Kadir; Göğüş, Fevzi Yılmaz
Objective We aimed to evaluate the depth of anaesthesia, perioperative haemodynamics, postoperative pain scores, analgesic consumption in patients receiving remifentanil- or alfentanil-based total intravenous anaesthesia for single-level lumbar discectomy. Methods Seventy patients undergoing discectomy were enrolled in the study. Patients were intravenously administered an initial bolus dose of 2 mg kg−1 propofol and 10 mcg kg−1 alfentanil or 1 mcg kg−1 remifentanil, followed by 6 mg kg−1 h−1 propofol and either 1 mcg kg−1 min−1 alfentanil or 0.25 mcg kg−1 min−1 remifentanil infusion. Bispectral index (BIS) values, mean arterial pressure, heart rate, end-tidal carbon dioxide and oxygen saturation were recorded. Postoperative pain scores at 0, 30 and 60 min were measured and recorded with additional opioid requirements. Results Postoperative pain scores at 0 and 30 min, total analgesic consumption and requirement for additional analgesics were significantly high in the remifentanil group. After the first hour, the pain scores were not significantly different. Mean arterial blood pressure was significantly low at 45 and 60 min preoperatively in the remifentanil group. In the remifentanil group, heart rate at 15, 30, 45, 60 min were significantly lower than those in the alfentanil group. BIS values of the two groups were not significantly different at any measurement time point. BIS values of remifentanil group at 30, 45, 60, 90 and 180 min significantly increased compared with those at 15 min. Conclusion Alfentanil provided more stable BIS and haemodynamic values preoperatively and less opioid consumption, along with lower pain scores, during the early postoperative period compared with remifentanil in patients undergoing single-level discectomy. PMID:27366550
Kim, Eun Mi; Jeon, Joo Hyun; Chung, Mi Hwa; Choi, Eun Mi; Baek, Seung Hwa; Jeon, Pil Hyun; Lee, Mi Hyeon
Background: While recovery from remifentanil is fast due to its rapid metabolism, it can induce hyperalgesia by activation of N-methyl-D-aspartic acid (NMDA) receptors. Therefore, administration of NMDA receptor antagonists such as ketamine is effective in relieving hyperalgesia caused by remifentanil. A previous study showed that nefopam administration before anesthesia combined with low-dose remifentanil reduced pain and analgesic consumption during the immediate postoperative period. We hypothesized that intraoperative infusion of nefopam during laparoscopic cholecystectomy would be as effective as ketamine in controlling pain during the acute postoperative period after sevoflurane and remifentanil based anesthesia. Methods: Sixty patients scheduled to undergo laparoscopic cholecystectomy were randomly divided into three groups. General anesthesia was maintained with sevoflurane and effect-site target concentration of remifentanil (4 ng/ml) in all patients. An intravenous bolus of nefopam (0.3 mg/kg) was given, followed by continuous infusion (65 µg/kg/h) in Group N (n=20). An intravenous bolus of ketamine (0.3 mg/kg) was administered, followed by continuous infusion (180 µg/kg/h) in Group K (n=20), and Group C received a bolus and subsequent infusion of normal saline equal to the infusion received by Group K (n=20). We compared postoperative Visual Analogue Scale (VAS) scores and analgesic requirements over the first 8 postoperative hours between groups. Results: The pain scores (VAS) and fentanyl requirements for 1 h after surgery were significantly lower in the nefopam and ketamine groups compared with the control group (p<0.05). There were no differences between the nefopam and ketamine groups. The three groups showed no differences in VAS scores and number of analgesic injections from 1 to 8 h after surgery. Conclusion: Intraoperative nefopam infusion during laparoscopic cholecystectomy reduced opioid requirements and pain scores (VAS) during the early
Esme, Hidir; Kesli, Recep; Apiliogullari, Burhan; Duran, Ferdane Melike; Yoldas, Banu
Objective: The aims of this study were to evaluate serum levels of acute phase reactants, such as CRP and cytokines (TNF-α and IL-6) in patients who have undergone thoracotomy and to investigate the effects of flurbiprofen on postoperative inflammatory response. Methods: Forty patients undergoing posterolateral thoracotomy were randomly divided into 2 groups of 20 each. Control group received tramadol (4 x 100 mg) intravenously for four days, and flurbiprofen group received both tramadol (4 x 100 mg) and flurbiprofen (2 x 100 mg). Blood samples were collected before surgery and at the 3th and 168th hours after surgical procedure to measure serum CRP, IL-6, and TNF-α. Pain visual analog scales were recorded daily during the first four postoperative days. Spirometric measurement of forced expiratory volume in the first second (FEV 1) was done before and four days after the operation. Results: The serum CRP, IL-6, and TNF-α levels in both groups increased significantly at 3th hour after thoracotomy. Serum TNF-α levels did not differ significantly between the groups at postoperative 4th day. However, IL-6 and CRP were significantly lower in flurbiprofen group than in control group at the same day (p<0.05). Visual analog scale was significantly lower in flurbiprofen group at 6th, 12th, 48th, 72th, and 96th hours postoperatively (p<0.05). The patients receiving flurbiprofen had higher FEV 1 values when compared with control group at postoperative 4th day. Conclusions: Patients undergoing thoracotomy showed reduced postoperative pain, mean additional analgesic consumption, and serum IL-6 and CRP levels, when flurbiprofen was added to systemic analgesic therapy. Analgesia with anti-inflammatory drug may contribute to the attenuation of the postoperative inflammatory response and prevent postoperative pain in patients undergoing thoracotomy. PMID:21448308
Sizer, Cigdem; Atici, Sait Selcuk; Arican, Sule; Karaibrahimoglu, Adnan; Kara, Inci
Objectives We aimed to assess the effects of levobupivacaine and of levobupivacaine + adrenaline administered during pediatric tonsillectomy on the postoperative period. Methods A total of 90 patients between the ages of five and twelve were divided randomly into two groups before tonsillectomy: levobupivacaine only (0.5%) 0.4 mg·kg−1 or levobupivacaine (0.5%) 0.4 mg·kg−1 + adrenaline (1 : 200.000) administered by means of peritonsillar infiltration. Primary outcomes were postoperative pain scores recorded at various intervals until 24 hours postoperatively. Secondary outcomes included postoperative nausea and vomiting (PONV), time to first oral intake, time to the first administration of analgesics and total consumption of analgesics, and the amount of bleeding for all children. Results In both groups, patients had the same postoperative pain scores and PONV rates, and equal amounts of analgesics were consumed up to 24 hours postoperatively. The two groups also had the same time until first oral intake, recovery time and time to the first analgesic request, and amount of bleeding. Conclusions Perioperative levobupivacaine infiltration on its own is a valid alternative to the combination of levobupivacaine + adrenaline for perioperative and postoperative effectiveness in pediatric tonsillectomy. This trial is registered with Australian New Zealand Clinical Trial Registry ACTRN: ACTRN12617001167358. PMID:28912639
Jan, Shumaila; Khan, Muhammad Rashid
Branched cancerwort, Kickxia ramosissima (Wall.) Janchen (Scrophulariaceae) is traditionally used for the treatment of inflammatory disorders such as rheumatism, diabetes, jaundice and for activation of immune system. Local communities also used this plant for the treatment of spleen enlargement, as febrifuge and in dysmenorrhea. In this investigation antipyretic, analgesic and anti-inflammatory effects of K. ramosissima have been evaluated. Dried powder of the whole plant of K. ramosissima was extracted with methanol (KRM) and partitioned with solvents to obtain the n-hexane (KRH), chloroform (KRC), ethyl acetate (KRE), n-butanol (KRB) and the residual aqueous (KRA) fraction. KRM and the derived fractions were analyzed for the phytochemical constituents, yeast induced pyrexia, analgesic and anti-inflammatory activities by using carrageenan and Freunds' complete adjuvant-induced paw edema model in rat. On account of appreciable effects of KRM in the aforesaid models, KRM was subjected to the carrageenan induced air pouch model in rat. The exudate of air pouch was analyzed for the count of neutrophils, monocytes, lymphocytes and WBCs and for the estimation of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO) and prostaglandin (PGE2). Phytochemical investigation of KRM indicated the existence of tannins, flavonoids, alkaloids, coumarins, cardiac glycosides, saponins, terpenoids and phlobatannins. Maximum concentration of total phenolic was determined in KRB followed by KRM while reverse was true for total flavonoids contents. KRM (200mg/kg) distinctly decreased the rectal temperature in yeast induced pyrexia comparable to standard, paracetamol. Pain sensation was effectively inhibited at 200mg/kg p.o. of KRM and KRB as manifested by a decrease (P<0.001) in count of writhing induced with acetic acid and increase of latency time in hot plate. Anti-inflammatory effects of KRM were evident and edema formation induced with carrageenan and Freunds
Meng, Yichen; Jiang, Heng; Zhang, Chenglin; Zhao, Jianquan; Wang, Ce; Gao, Rui; Zhou, Xuhui
Postoperative analgesia remains a challenge for orthopedic surgeons. The aim of this meta-analysis is to compare the efficacy of epidural analgesia (EA) and intravenous patient-controlled analgesia (IV-PCA) following major spine surgery. We searched electronic databases, including the PubMed, EMBASE, Ovid and Cochrane databases, for randomized controlled trials (RCTs) published before June 2016. The quality of the included trials was assessed using the Cochrane risk-of-bias tool. Random effects models were used to estimate the standardized mean differences (SMDs) and relative risks (RRs), with the corresponding 95% confidence intervals (CI). Subgroup analyses stratified by the type of epidural-infused medication and epidural delivery were also performed. A total of 17 trials matched the inclusion criteria and were chosen for the following meta-analysis. Overall, EA provided significantly superior analgesia, higher patient satisfaction and decreased overall opioid consumption compared with IV-PCA following major spine surgery. Additionally, no differences were found in the side effects associated with these two methods of analgesia. Egger’s and Begg’s tests showed no significant publication bias. We suggest that EA is superior to IV-PCA for pain management after major spine surgery. More large-scale, high-quality trials are needed to verify these findings. PMID:28243145
McNally, L M; Barbour, M E; O'Sullivan, D J; Jagger, D C
The sale of over-the-counter pain relief medication has increased dramatically in recent years, and typically amounts to several hundred thousands of pounds per year in the UK. Many soluble analgesic preparations contain citric acid, and it has been suggested that these formulations may cause dental erosion. The aim of this study was to investigate the effect of some over-the-counter analgesics on tooth surface loss from human enamel. Six commonly available analgesics were chosen for this study and the effect of immersing unerupted human enamel was examined using non-contact optical profilometry. Two of the six analgesics investigated caused no detectable erosion (Boots soluble aspirin and Anadin Extra). Three caused statistically significant enamel erosion, but this was very slight and is thought to be clinically insignificant (Alka Seltzer, Panadol and Solpadeine). Only one analgesic caused possible potentially clinical significant enamel erosion. Further studies are needed to determine whether Aspro causes clinically significant enamel erosion.
Skoglund, L A; Skjelbred, P; Fyllingen, G
Acetaminophen (APAP) 1000 mg, APAP 2000 mg, the combination of APAP 1000 mg plus codeine phosphate 60 mg (APAPCOD), and placebo (PBO) were compared in a 6-hour, randomized, single-dose, double-blind, parallel-group analgesic trial. All active treatments were statistically superior (p less than 0.05) to placebo for 4 hours after medication with respect to pain intensity (PI) and pain intensity difference (PID), and up to 3 hours regarding pain relief (PAR). The combination scored better than all other treatments on the summary analgesic efficacy measures sum PI (SUMPI), sum PID (SPID), and total PAR (TOTPAR). The combination was statistically superior to APAP 1000 mg on SUMPI, TOTPAR and maximum PAR (MAXPAR). Acetaminophen 2000 mg showed marginal numerical superiority over 1000 mg for SUMPI, but was not statistically superior for any summary efficacy measure. The 2000-mg dose was numerically inferior to APAPCOD for every summary efficacy measure and statistically inferior regarding SPID and MAXPAR. We concluded that codeine 60 mg added to acetaminophen 1000 mg offers analgesic advantages, and acetaminophen reaches an analgesic ceiling effect at 1000 mg using the dental pain model.
Koh, Jae Chul; Lee, Jinae; Kim, So Yeon; Choi, Sumin; Han, Dong Woo
Abstract In this retrospective analysis of 10,575 patients who used fentanyl-based intravenous patient-controlled analgesia (IV-PCA) after surgery, we evaluated difference between young and elderly patients on their characteristic of adverse effects. We reviewed the data collected from the patients who were provided IV-PCA for pain control following elective surgery under either general or spinal anesthesia between September 2010 and March 2014. Postoperative pain, incidence of PCA-related adverse effects, and risk factors for the need of rescue analgesics and antiemetics for postoperative 48 hours were analyzed. Pain intensity (numerical rating scale [NRS]) at postoperative 6 to 12 hours (4.68 vs 4.58, P < 0.01) and incidence of nausea or vomiting (23.8% vs 20.6%, P < 0.001) were higher in young patients, while incidence of PCA discontinuation (9.9% vs 11.5%, P < 0.01) and sedation (0.1% vs 0.7%, P < 0.001) was higher in elderly patients. Despite larger fentanyl dose used, a greater proportion of young patients required rescue analgesics (53.8% vs 47.9%, P < 0.001) while addition of ketorolac was effective in reducing postoperative pain. Despite lower incidence of postoperative nausea and vomiting (PONV), a larger proportion of elderly patients required rescue antiemetics (10.1% vs 12.2%, P < 0.001) while addition of ramosetron was effective in reducing PONV. In conclusion, when fentanyl-based IV-PCA is used for postoperative pain control, a larger proportion of young patients may require rescue analgesics while elderly patients may require more rescue antiemetics. The addition of ketorolac or ramosetron to the PCA of young and elderly patients can be effective to prevent rescue analgesics or antiemetics use. PMID:26559296
Alebouyeh, Mahmoud Reza; Imani, Farnad; Rahimzadeh, Poupak; Entezary, Saeed Reza; Faiz, Seyed Hamid Reza; Soraya, Parisa
Background: Opiate is used in patient-controlled intravenous analgesia pumps (PCIA) for controlling pain in post-surgical patients. Other drugs are remarkably added to opioid pumps to enhance quality, lengthen analgesia, and reduce side effects. Lidocaine, a local anesthetic which inhibits sodium channels, has anesthetic and analgesic effects when injected locally or intravenously. The objective of this study is to evaluate the analgesic effects of adding lidocaine 1% to different doses of morphine via IV pump to patient-controlled analgesia (PCA) after orthopedic surgeries. Materials and Methods: In a randomized clinical trial, 60 patients who had undergone orthopedic surgery of lower extremities were divided into three equal groups to control postoperative pain. Intravenous pump with 5 ml/h flow rate was used as the analgesic method. The solution consisted of lidocaine 1% plus 20 mg morphine for the first group, lidocaine 1% plus 10 mg morphine for the second group, and only 20 mg morphine for the third group (control group). Patients were checked every 12 h, and Visual Analog Scale (VAS), extra opioid doses, nausea/vomiting, and sedation scale were examined. Results: Pain score was lower in the first group compared to the other two groups. Mean VAS was 2.15 ± 0.2, 2.75 ± 0.2, and 2 ± 0.25 on the first day and 1.88 ± 0.1, 2.74 ± 0.3, and 2.40 ± 0.3 on the second day, respectively, in the three groups and the difference was statistically significant (P < 0.01 and <0.05, respectively). Also, 10% of patients in the first group needed extra opioid doses, while this figure was 30% in the second group and 25% in the third group (P < 0.01). Nausea/vomiting and sedation scores were not statistically different among the three groups. Conclusion: Compared to lidocaine 1% plus 10 mg morphine or 20 mg morphine alone in PCIA, adding lidocaine 1% to 20 mg morphine decreases the pain score and opioid dose after orthopedic surgeries without having side effects. PMID
Johnson, Sarah; Coxon, Matthew
Virtual reality (VR) technology may serve as an effective non-pharmacological analgesic to aid pain management. During VR distraction, the individual is immersed in a game presented through a head-mounted display (HMD). The technological level of the HMD can vary, as can the use of different input devices and the inclusion of sound. While more technologically advanced designs may lead to more effective pain management the specific roles of individual components within such systems are not yet fully understood. Here, the role of supplementary auditory information was explored owing to its particular ecological relevance. Healthy adult participants took part in a series of cold-pressor trials submerging their hand in cold water for as long as possible. Individual pain tolerances were measured according to the time (in seconds) before the participant withdrew their hand. The concurrent use of a VR game and the inclusion of sound was varied systematically within participants. In keeping with previous literature, the use of a VR game increased pain tolerance across conditions. Highest pain tolerance was recorded when participants were simultaneously exposed to both the VR game and supplementary sound. The simultaneous inclusion of sound may therefore play an important role when designing VR to manage pain.
Göymen, Abdullah; Şimşek, Yavuz; Özdurak, Halil İbrahim; Özkaplan, Şükran Esra; Akpak, Yaşam Kemal; Özdamar, Özkan; Oral, Serkan
To assess the effect of povidone iodine versus benzalkonium chloride, which were applied preoperatively for vaginal disinfection in caesarean sections, on postoperative factors. One hundred and twenty patients underwent elective caesarean section were divided into three groups using the simple randomisation method: Group 1 (povidone iodine, n: 41); Group 2 (benzalkonium chloride, n: 39); Group 3 (control group, n: 40). Demographic data, duration of operation, amount of bleeding, postoperative pain, time to first flatulence and defaecation, haematological parameters on postoperative day 1 were compared between three groups. Pain evaluation was performed at 6th and 24th postoperative hour using Visual Analogue Scale. No statistically significant differences were detected between the groups in demographic characteristics. There were no significant differences between the groups with respect to the duration of operation and hospital stay. The patients in the group who underwent povidone iodine vaginal cleansing had statistically significantly less postoperative pain as compared to control group. No difference was observed between the groups in haematological parameters other than C-reactive protein (CRP); however, CRP levels at 24th post-operative hour were significantly lower in Group 1 compared to the other groups. The preoperative vaginal cleansing with povidone iodine could reduce the postoperative pain, analgesic need and infection parameter.
Sin, Wai Man; Chow, Ka Ming
Unrelieved postoperative pain may have a negative impact on the physiological and psychological well-being of patients. Pharmacological methods are currently used to relieve such pain in gynecological patients; however, inadequate pain control is still reported, and the use of nonpharmacological pain-relieving methods is increasingly being advocated, one of which is music therapy. The purpose of this literature review was to identify, summarize, and critically appraise current evidence on music therapy and postoperative pain management among gynecological patients. A systematic search of MEDLINE, CINAHL, PsycINFO, British Nursing Index, and Allied and Complementary Medicine was conducted using the search terms music, gynecological, pain, surgery, operative, and post-operative to identify relevant articles in English from 1995 to the present. All identified articles were assessed independently for inclusion into review. A total of 7 articles were included after removal of duplicates and exclusion of irrelevant studies. All the included studies assessed the effects of music therapy on postoperative pain intensity, and three of them measured pain-related physiological symptoms. The findings indicated that music therapy, in general, was effective in reducing pain intensity, fatigue, anxiety, and analgesic consumption in gynecological patients during the postoperative period. It is recommended as an adjunct to pharmacological pain-relieving methods in reducing postoperative pain. Future researches on music therapy to identify the most effective application and evaluate its effect by qualitative study are recommended. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.
Gené, R M; Segura, L; Adzet, T; Marin, E; Iglesias, J
Heterotheca inuloides Cass. (Asteraceae) is used in the traditional medicine of Mexico. The aqueous extract obtained from the flowers of H. inuloides was assessed for anti-inflammatory activity by carrageenan-induced edema test. At 100 mg/kg, i.p, it produced 29% inhibition of inflammation. Ethyl ether (HI-1), butanol (HI-2) and aqueous fraction (HI-3) were obtained from the aqueous extract. The biological assay, by carrageenan-induced edema test, gave the following values (% inhibition): HI-1, 19.9; HI-2, 58.0 and HI-3, 30.0. HI-2 was significantly more effective than HI-1 and HI-3. The dose-effect curve of HI-2 was obtained and the calculated ED50 was 29.7 (22.5-39.2) mg/kg. The peritoneal examination after the treatment with HI-2 showed that the anti-inflammatory action of H. inuloides was not due to an irritating effect at the injection site. At 50-100 mg/kg, i.p., HI-2 inhibited inflammation induced by dextran (38.9-68.1% inhibition) and arachidonic acid (0-33.9%). No effect was observed at the same doses for zymosan or C16-paf-induced edema. In addition, HI-2 reduced abdominal constrictions in mice following injection of acetic acid: at 50-100 mg/kg, it gave 73.8-78.2% inhibition. The ulcerogenic assay showed that ulcer indices after HI-2 i.p. treatment were 0.5 +/- 0.5 at 50 mg/kg and 1.2 +/- 0.4 at 100 mg/kg. The results showed related anti-inflammatory activity and the analgesic effect of HI-2.
Kristensen, David M; Mazaud-Guittot, Séverine; Gaudriault, Pierre; Lesné, Laurianne; Serrano, Tania; Main, Katharina M; Jégou, Bernard
Paracetamol and NSAIDs, in particular acetylsalicylic acid (aspirin) and ibuprofen, are among the most used and environmentally released pharmaceutical drugs. The differences in international trends in the sale and consumption of mild analgesics reflect differences in marketing, governmental policies, habits, accessibility, disease patterns and the age distribution of each population. Biomonitoring indicates ubiquitous and high human exposure to paracetamol and to salicylic acid, which is the main metabolite of acetylsalicylic acid. Furthermore, evidence suggests that analgesics can have endocrine disruptive properties capable of altering animal and human reproductive function from fetal life to adulthood in both sexes. Medical and public awareness about these health concerns should be increased, particularly among pregnant women.
Maiese, Brett A; Pham, An T; Shah, Manasee V; Eaddy, Michael T; Lunacsek, Orsolya E; Wan, George J
To assess the impact on hospitalization costs of multimodal analgesia (MMA), including intravenous acetaminophen (IV-APAP), versus IV opioid monotherapy for postoperative pain management in patients undergoing orthopedic surgery. Utilizing the Truven Health MarketScan(®) Hospital Drug Database (HDD), patients undergoing total knee arthroplasty (TKA), total hip arthroplasty (THA), or surgical repair of hip fracture between 1/1/2011 and 8/31/2014 were separated into postoperative pain management groups: MMA with IV-APAP plus other IV analgesics (IV-APAP group) or an IV opioid monotherapy group. All patients could have received oral analgesics. Baseline characteristics and total hospitalization costs were compared. Additionally, an inverse probability treatment weighting [IPTW] with propensity scores analysis further assessed hospitalization cost differences. The IV-APAP group (n = 33,954) and IV opioid monotherapy group (n = 110,300) differed significantly (P < 0.0001) across baseline characteristics, though the differences may not have been clinically meaningful. Total hospitalization costs (mean ± standard deviation) were significantly lower for the IV-APAP group than the IV opioid monotherapy group (US$12,540 ± $9564 vs. $13,242 ± $35,825; P < 0.0001). Medical costs accounted for $701 of the $702 between-group difference. Pharmacy costs were similar between groups. Results of the IPTW-adjusted analysis further supported the statistically significant cost difference. Patients undergoing orthopedic surgery who received MMA for postoperative pain management, including IV-APAP, had significantly lower total costs than patients who received IV opioid monotherapy. This difference was driven by medical costs; importantly, there was no difference in pharmacy costs. Generalizability of the results may be limited to patients admitted to hospitals similar to those included in HDD. Dosing could not be determined, so it was not possible to quantify
Xu, Bo; Wang, Zhi-Ping; Wang, Yan-Juan; Lu, Pei-Hua; Wang, Li-Jun; Wang, Xiao-Hai
Opioid analgesics are the most common therapeutic analgesic for acute pain. In this study, the toxicological and pharmacological features of a group of opioid analgesics were characterized by the motility of human sperm. Aliquots of sperm were incubated with various concentrations of opioid analgesics in vitro. Computer-assisted sperm analysis was used to assess sperm motility at 15 minutes, 2 hours, and 4 hours after drug addition to the medium. Butorphanol and dezocine showed marked reduction of motility after incubation with sperm for 15 minutes. Butorphanol was more effective than dezocine in immobilizing sperm. Other opioids studied, such as fentanyl, alfentanil, and sufentanil, showed only partial inhibitory activity. Based on the data reported herein, we have found that butorphanol and dezocine exert a sperm-immobilizing effect. However, fentanyl, alfentanil, and sufentanil exhibit only partial inhibition of sperm motility. Given the increasing use of opioids and their potential effect on sperm motility, these findings are greatly relevant to male reproductive health.
Lin, Hong-Qi; Jia, Dong-Lin
The pain following gynecological laparoscopic surgery is less intense than that following open surgery; however, patients often experience visceral pain after the former surgery. The aim of this study was to determine the effects of preemptive ketamine on visceral pain in patients undergoing gynecological laparoscopic surgery. Ninety patients undergoing gynecological laparoscopic surgery were randomly assigned to one of three groups. Group 1 received placebo. Group 2 was intravenously injected with preincisional saline and local infiltration with 20 mL ropivacaine (4 mg/mL) at the end of surgery. Group 3 was intravenously injected with preincisional ketamine (0.3 mg/kg) and local infiltration with 20 mL ropivacaine (4 mg/mL) at the end of surgery. A standard anesthetic was used for all patients, and meperidine was used for postoperative analgesia. The visual analogue scale (VAS) scores for incisional and visceral pain at 2, 6, 12, and 24 h, cumulative analgesic consumption and time until first analgesic medication request, and adverse effects were recorded postoperatively. The VAS scores of visceral pain in group 3 were significantly lower than those in group 2 and group 1 at 2 h and 6 h postoperatively (P<0.05 and P<0.01, respectively). At 2 h and 6 h, the VAS scores of incisional pain did not differ significantly between groups 2 and 3, but they were significantly lower than those in group 1 (P<0.01). Groups 1 and 2 did not show any differences in visceral pain scores at 2 h and 6 h postoperatively. Moreover, the three groups showed no statistically significant differences in visceral and incisional pain scores at 12 h and 24 h postoperatively. The consumption of analgesics was significantly greater in group 1 than in groups 2 and 3, and the time to first request for analgesics was significantly longer in groups 2 and 3 than in group 1, with no statistically significant difference between groups 2 and 3. However, the three groups showed no significant difference
Frantz, Kariza Aiko; Moura Filho, Edney de Rezende; Abud, Murilo Batista; Avila, Marcos Pereira de; Magacho, Leopoldo
To compare the analgesic effect between dipyrone, 90 mg etoricoxib, and placebo after excision of primary pterygium with conjunctival autograft. Prospective, randomized, double-masked clinical trial. Three groups of 26 patients (one eye per patient) were submitted to surgery and received the study drugs for five days after surgery. A scale of pain was used, graduated from zero to ten, for patient evaluation in the first, third and fifth postoperative days. The pain was classified as absent (zero), mild (1 to 3), moderate (4 to 7) and severe (8 to 10). Statistical analysis was performed with the SPSS, version 11.5. A statistically significant difference was found between etoricoxib and dipyrone in the first and third postoperative days (p=0.001 and p=0.01; respectively). Etoricoxib was superior to placebo only in the first postoperative day (p=0.04). There was no significance in the comparison between dipyrone and placebo. Analgesia of etoricoxib was superior to placebo in the first postoperative day and to dipyrone in the third and fifth days after excision of primary pterygium with conjunctival autograft. There was no significant difference between dipyrone and placebo in all time points.
Yun, So Hui; Park, Jong Cook; Kim, Sang Rim; Choi, Yun Suk
The beneficial effects of dexmedetomidine (DEX) have not been extensively investigated in elderly patients receiving spinal anesthesia. This study evaluated the effects of intravenous DEX infusion on stress and hemodynamic response, as well as on postoperative analgesia in elderly patients undergoing total knee arthroplasty (TKA). We randomly allocated 45 adult patients to 3 patient groups (n=15 each): uni-saline group patients underwent unilateral TKA with saline administration, uni-DEX group patients underwent unilateral TKA with DEX administration, and bilateral-DEX group patients underwent bilateral TKA with DEX administration. Serum interleukin-6 (IL-6) levels were significantly lower in the bilateral-DEX group than in the uni-saline group 6 and 24h postoperatively, and were negatively correlated with total DEX dosage 24h postoperatively. Bradycardia occurred more frequently in the uni-DEX and bilateral-DEX groups than in the uni-saline group. The total dose of required supplementary analgesics was significantly higher in the uni-saline group than in the uni-DEX and bilateral-DEX groups 6h postoperatively. The results indicate that perioperative intravenous DEX administration decreases postoperative serum IL-6 levels in patients undergoing bilateral TKA, and has a postoperative analgesic effect in patients undergoing unilateral or bilateral TKA.
Arregui-Martínez de Lejarza, L M; Vigil, M D; Pérez Pascual, M C; Cardona-Valdés, A; Pérez de Cossío, J M
Intravenous regional anesthesia (i.v.r.) is a safe, effective technique for surgery on the upper extremities, but it provides no postoperative analgesia. The aim of this study was to evaluate the analgesic efficacy of ketorolac during and after surgery with i.v.r. induced by lidocaine. A double blind, placebo-controlled clinical trial. Twenty-six patients undergoing elective surgery on the upper extremities under i.v.r. were studied. In the anteroom of the operating theater, an anesthesiologist prepared the anesthetic solution to be administered from two syringes. One contained 3 mg/kg of 0.5% lidocaine (0.6 ml/kg). The second syringe (2 ml) contained 1 ml of 0.9% saline solution for the control group or 1 ml with 30 mg of ketorolac for the treatment group. A second anesthesiologist received the patient in the operating theater and used the syringes provided to induce the blockade. After releasing the pneumatic tourniquets we assessed the appearance of postoperative pain on a visual analog scale over the first 24 hours. The dats were compared using parametric (Student t test) and non parametric tests (Mann-Whitney U test and Fisher's exact test). No significant differences in the characteristics or hemodynamic parameters analyzed were found between the two groups. Nor did we find any differences in analgesia during surgery. Ten of the 13 patients (77%) in the control group required analgesia within the first two hours, whereas none of the patients in the treatment group required analgesia during that time (p < 0.0001). There were no statistically significant differences between the two groups in the total amount administered altogether, both during and after surgery. No local or systemic side effects were observed.
Dobbins, Stephanie; Brown, Nancy O; Shofer, Frances S
In this prospective, randomized, blinded study, 68 clinically healthy cats that had onychectomy (n = 20), onychectomy and castration (n = 20), or onychectomy and ovariohysterectomy (n = 28) were randomly assigned to one of four postoperative analgesic treatment groups: buprenorphine (0.01 mg/kg body weight, intramuscularly [IM]), oxymorphone hydrochloride (0.05 mg/kg body weight, IM), ketoprofen (2 mg/kg body weight, IM), and placebo (physiological saline). Sedation scores, visual analog pain scores, cumulative pain scores, serum cortisol concentration, and appetite were used to assess postoperative analgesic effect. Buprenorphine demonstrated the highest efficacy with the lowest cumulative pain scores and serum cortisol levels.
Mony, Deepthi; Kulkarni, Deepak
Introduction Analgesia pre-emptively administered effect-ively aid in management of pain. Pre-emptive analgesia is anti-nociceptive treatment which prevents altered central sensitization of afferent inputs. Aim To compare and evaluate the pre-emptive analgesic efficacy of preoperatively administered ketorolac and diclofenac for controlling postoperative pain after third molar surgery. Materials and Methods A total of 50 patients with symmetrically impacted third molars were divided into two groups, 30mg intramuscular injection of ketorolac and 75 mg diclofenac sodium were used in the respective groups. The visual analogue scale was used to assess post operative pain for three days and the patients were also evaluated for the number of rescue analgesia. Results The data was statistically evaluated with paired t- test. The maximum time taken for pain perception for Group A Ketoralac was 5.48 hrs and Group B Diclofenac sodium was 4.9 hrs and p=0.235 which was not significant. The mean number of tablets taken by the patients in the first three post operative days was 3.24 in Group A i.e., Ketorolac and 4.04 in Group B i.e., Diclofenac sodium. The values were compared using the paired t test. The p value = 0.004, which was significant. Conclusion Ketoralac showed better pre-emptive analgesic effect for post-operative pain management after third molar extraction. The immediate post-operative pain free period provided by both ketorolac and diclofenac by intramuscular route was same. PMID:27504398
Bugada, Dario; Lavand'homme, Patricia; Ambrosoli, Andrea Luigi; Klersy, Catherine; Braschi, Antonio; Fanelli, Guido; Saccani Jotti, Gloria M R; Allegri, Massimo
The study objective is to identify differences in postoperative pain management according to different analgesic treatments, targeting 2 main pathways involved in pain perception. The design is a randomized, parallel groups, open-label study. The setting is in an operating room, postoperative recovery area, and surgical ward. There are 200 patients undergoing open inguinal hernia repair (IHR) with tension-free technique (mesh repair). The intervention is a randomization to receive ketorolac (group K) or tramadol (group T) for 3 days after surgery. The measurements are differences in analgesic efficacy (numeric rating scale [NRS]) in the postoperative (up to 5 days) period, chronic pain incidence (1 and 3 months), side effects, and complications. We found no differences in analgesic efficacy (NRS value ≥4 in the first 96 hours: 26% in group K vs 32% in group T, P = .43); the proportion of patients with NRS ≥4 was similar in both groups, and the time trajectories were not significantly different (P for interaction = .24). Side effects were higher (12% vs 6%) in the tramadol group, although not significantly (P = .14), with a case of bleeding in the ketorolac group and higher incidence of constipation in tramadol group. One patient in each group developed chronic pain. Ketorolac or weak opioids are equally effective on acute pain and on persistent postsurgical pain development after IHR, and drug choice should be based on their potential side effects and patient's comorbidities. Further studies are needed to standardize the most rational approach to prevent persistent postsurgical pain after IHR. Copyright © 2015 Elsevier Inc. All rights reserved.
Faunø, Peter; Lund, Bent; Christiansen, Svend Erik; Gjøderum, Ole; Lind, Martin
To evaluate the effect of a hamstring block for postoperative pain management using 20 mL of 0.25% bupivacaine compared with placebo after anterior cruciate ligament (ACL) reconstruction with a hamstring autograft. In a 3-month period, 45 patients undergoing ACL reconstruction with a hamstring autograft who all received a femoral nerve block were randomized to receive either 20 mL of 0.25% bupivacaine or 20 mL of saline water administered through a catheter into the donor-site space. The patients and recovery staff were blinded to the treatment. Postoperative donor-site pain was evaluated subjectively by the patients using a pain score (Likert scale from 0 to 10). The pain was registered for each hour in the first 6 hours and thereafter once daily for 8 days. Furthermore, the requirement for postoperative analgesic medicine was registered. The hamstring block group (n = 23) had significantly less pain for each of the first 6 postoperative hours. The pain score was reduced from 4.2 to 2.3 (95% confidence interval, 1.3 to 3.3) (P = .01) in the first hour and from 2.8 to 1.3 (95% confidence interval, 0.6 to 1.9) in the sixth hour, and there was a significantly lower overall requirement for early postoperative fentanyl, reduced from a mean of 58 to 35 μg (P = .02), and morphine, reduced from a mean of 10 to 6 mg (P = .04). After 6 hours, there was no difference in the pain level and use of analgesics between the 2 groups. With the use of a donor-site block in hamstring ACL reconstruction, the donor-site pain level, as well as the overall requirement for fentanyl and morphine, was significantly reduced in the first 6 postoperative hours. No effect of the donor-site block was seen after 6 hours. Level I, therapeutic, randomized controlled study. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
Smith, Howard S
Although there is no "ideal analgesic," scientists and clinicians alike continue to search for compounds with qualities which may approach the "ideal analgesic." Characteristics of an "ideal" analgesic may include: the agent is a full agonist providing optimal/maximal analgesia for a wide range/variety of pain states (e.g., broad spectrum analgesic activity), it does not exhibit tolerance, it produces no unwanted effects and minimal adverse effects, it has no addictive potential, it does not facilitate pain/hyperalgesia, it has a long duration, it has high oral bioavailability, it is not vulnerable to important drug interactions, it is not significantly bound to plasma proteins, it has no active metabolites, it has linear kinetics, and it is eliminated partly by hydrolysis to an inactive metabolite (without involvement of oxidative and conjugative enzymes). Investigators have concentrated on ways to alter existing analgesics or to combine existing analgesic compounds with compounds which may improve efficacy over time or minimize adverse effects. The addition of an analgesic with a second agent (which may or may not also be an analgesic) to achieve a "combination analgesic" is a concept which has been exploited for many years. Although there may be many reasons to add 2 agents together in efforts to achieve analgesia, for purposes of this article - reasons for combining an opioid with a second agent to produce a combination opioid analgesic may be classified into 6 major categories: 1.) combinations to prolong analgesic duration; 2.) combinations to enhance or optimize analgesic efficacy (e.g., analgesic synergy); 3.) combinations to diminish or minimize adverse effects; 4.) combinations to diminish opioid effects which are not beneficial (or contrariwise to or enhance beneficial opioid effects); 5.) combinations to reduce opioid tolerance/opioid-induced hyperalgesia; and 6.) combinations to combat dependency issues/addiction potential/craving sensations
Selcuk, Selcuk; Api, Murat; Polat, Mesut; Arinkan, Arzu; Aksoy, Bilge; Akca, Tijen; Karateke, Ates
The aim of this study was to assess the effects of preemptive and preclosure analgesia on postoperative pain intensity in patients undergoing different levels of laparoscopic surgery. Two hundred and twenty-six patients who underwent laparoscopic gynecological surgery were enrolled in this quasi-randomized, prospective, placebo controlled study. The operations were classified as level 1 or level 2 according to the extent of the surgery. Lidocaine 1 % was administered at the port sites before making the incision in the preincisional study group. In preincisional control group, same amount of saline was infiltrated in same manner. Lidocaine 1 % was infiltrated at the port site immediately after removing the trocars in preclosure study group. In preclosure control group, the same amount of saline was infiltrated in the same manner. Postoperative pain intensity was evaluated by linear visual analogue scale. It was found that preclosure lidocaine infiltration was more effective on postoperative pain intensity than its placebo group in level 1 and level 2 surgery groups at 1 and 2 h postoperatively. The administration of preincisional lidocaine improved postoperative pain scores significantly more than its placebo group in level 1 laparoscopic surgery group at 1 and 2 h postoperatively and in level 2 laparoscopic surgery group at 1 h postoperatively. Lidocaine infiltration at port sites had beneficial effects on pain intensity in the early postoperative period after laparoscopic gynecological surgery. However, the results of present study showed that the analgesic effect mechanism of local anesthetic was unrelated to the preemptive analgesia hypothesis.
Eftekhar, Behrooz; Moghimipour, Eskandar; Pourakbar Jahandideh, Pejman; Jalali, Sahar; Mahmoudian, Mahsa
Background Pain experience makes a serious anxiety for both patient and clinician before and after root canal treatment. Pain is a complex psychophysiologic phenomenon. Objectives The aim of this randomized control trial study was to evaluate the analgesic effect of Odontopaste® and a corticosteroid containing compound medicament between root canal therapy appointments. Materials and Methods One hundred and twenty lower first and second mandibular molars with spontaneous pain and sensitivity to percussion were selected and divided into three groups (40 patients per each group). After root canal preparation, patients were entered one of these groups randomly. Root canals in group 1 were dressed with Odontopaste, in group 2 with a compound intracanal medicament, and in group 3 with placebo. Patients determined their pain rate and percussion sensitivity on Heft-parker VAS diagram, before the first appointment and 24 hours and 7 days after that. Results Spontaneous pain and Percussion sensitivity score averages of 24 hours after the first appointment in group 1 and group 2 were less than group 3, which indicates statistically significant difference between these groups. There was no statistically significant difference between these groups after 7 days neither on spontaneous pain nor percussion sensitivity. Conclusions Odontopaste® and compound intracanal medicaments resulted in statistically significant reduction in postoperative pain and percussion sensitivity after 24 hours, but there was no statistically significant difference after 7 days with placebo. PMID:24624209
Nnaji, Chimaobi T; Onajin-Obembe, Bisola; Ebirim, Longinus
Postoperative pain is a common complaint in day-case inguinal herniotomy, thus there is a need to provide effective analgesia. This study compared the postoperative analgesic effects of the combinations of caudal-bupivacaine and rectal diclofenac with caudal-bupivacaine and rectal-paracetamol in children scheduled for daycase inguinal-herniotomy. Ninety children of ASA I scheduled for elective day-case inguinal-herniotomy were randomly assigned into Group A (1ml/kg of 0.25% caudal-bupivacaine and 1mg/kg rectal-diclofenac), Group B (1ml/kg of 0.25% caudal-bupivacaine and 30mg/kg rectal paracetamol) and Group C (1ml/kg of 0.25% caudal-bupivacaine). The duration of analgesia, pain scores, postoperative analgesic consumption and side effects were assessed and recorded. Data collected was analyzed with the statistical package for social sciences 17 for windows. Eighty-seven children completed the study, and it was found that the duration of analgesia was prolonged in Group A compared to Groups B and C (p<0.01). Caudal-bupivacaine and rectal-diclofenac combination provides a more prolonged postoperative analgesia, and lower pain score compared to caudal-bupivacaine and rectal-paracetamol combination or caudal-bupivacaine alone. Level 1 evidence treatment study. Randomized controlled trials with adequate statistical power to detect differences (narrow confidence intervals) and follow up >80%. Copyright © 2017 Elsevier Inc. All rights reserved.
The use of analgesic drugs in postoperative patients: the neglected problem of pain control in intensive care units. An observational, prospective, multicenter study in 128 Italian intensive care units.
Bertolini, Guido; Minelli, Cosetta; Latronico, Nicola; Cattaneo, Alessandro; Mura, Giorgio; Melotti, Rita M; Iapichino, Gaetano
The use of analgesic drugs in patients admitted to Italian intensive care units (ICUs) was assessed. An observational, prospective, cohort study was conducted, involving all adult patients admitted during a 1-month period in 128 Italian general ICUs. The use of analgesic drugs was evaluated for the first 2 postoperative days in surgical patients who stayed in ICU for at least 2 days. We observed 661 postoperative patients who underwent elective (72%) or emergency surgery. Of the patients with an ICU stay of at least 2 days, 49% did not receive any opioids in the first 48 postoperative hours, and more than 35% did not receive any analgesic at all. The most used opioid was fentanyl, followed by morphine and buprenorphine. Among the 336 patients who received at least one opioid, as many as 42% had only a single bolus per day. Pain control was reported as the reason for drug use in 54.5% of opioid administrations, while control of anxiety covered 10.3% of them. The probability of receiving an opioid was lower for patients in coma. Management of postoperative pain in Italian ICUs was insufficient, particularly in neurosurgical and comatose patients. A general lack of knowledge about pain and misconceptions about pain drugs may be at the basis of these results.
Liu, Hui; Qian, Xiao-Yan; An, Jian-Xiong; Liu, Cai-Cai; Jiang, Yi-De; Cope, Doris K; Williams, John P
Electroacupuncture (EA) is widely applied to treat neuropathic pain. Brachial plexus neuralgia (BPN) is a common form of chronic persistent pain. Few studies have evaluated the analgesic effects and mechanism of EA using the novel animal model of BPN. To observe the curative effects of repeated EA on curing BPN induced by administration of cobra venom to the lower trunk of the right brachial plexus. Controlled animal study. Department of Anesthesiology, Pain Medicine & Critical Care Medicine, Aviation General Hospital of China Medical University. Sixty-six adult male Sprague-Dawley rats were equally and randomly divided into the following groups: normal control (NC), brachial plexus neuralgia (BPN), BPN with sham EA stimulation, BPN with EA stimulation starting on postoperative day 1 (EA1), and BPN with EA stimulation starting on postoperative day 12 (EA12). The BPN model was established by administration of cobra venom to the lower trunk of the right brachial plexus. On postoperative day 1 or day 12, EA (constant aquare wave, 2 Hz and 100 Hz alternating frequencies, intensities ranging from 1 - 1.5 - 2 mA) was applied to the right "Shousanli" (LI10) and "Quchi" (LI11) acupoints for 30 minutes, once every other day for 12 times in both groups. Mechanical withdrawal thresholds (MWT) were tested with von Frey filaments. Video recordings were conducted to analyze the spontaneous exploratory behaviors. Moreover, the organizational and structural alterations of the right brachial plexus and cervical cord (C8-T1) were examined via light and electron microscopy. Following the production of the BPN model, the MWT of both ipsilateral and contralateral paws demonstrated a profound decrease (P < 0.05). But after EA interventions, the MWT showed a significant increase (P < 0.05). In comparison to the EA12 group, the analgesic effects of the EA1 group were more significant, and similar results were observed in exploratory behaviors. However, grooming behaviors did not
Nickerson, Paul; Tighe, Patrick; Shickel, Benjamin; Rashidi, Parisa
Response to prescribed analgesic drugs varies between individuals, and choosing the right drug/dose often involves a lengthy, iterative process of trial and error. Furthermore, a significant portion of patients experience adverse events such as post-operative urinary retention (POUR) during inpatient management of acute postoperative pain. To better forecast analgesic responses, we compared conventional machine learning methods with modern neural network architectures to gauge their effectiveness at forecasting temporal patterns of postoperative pain and analgesic use, as well as predicting the risk of POUR. Our results indicate that simpler machine learning approaches might offer superior results; however, all of these techniques may play a promising role for developing smarter post-operative pain management strategies.
Gao, Tianle; Hao, Jingxia; Wiesenfeld-Hallin, Zsuzsanna; Wang, Dan-Qiao; Xu, Xiao-Jun
Sinomenine is an alkaloid originally isolated from the root of the plant Sinomenium acutum. It is used in traditional medicine in China to treat rheumatic arthritis. In the present study, we evaluated the potential antinociceptive effects of sinomenine in rodents with nociceptive, inflammatory and neuropathic pain. In normal rats and mice, systemic sinomenine produced moderate antinociceptive effect in the hot plate and tail flick tests. Sinomenine also exerted analgesic effects on mechanical and heat hypersensitivity in mice after carrageenan induced inflammation. Finally, sinomenine effectively alleviated mechanical and cold allodynia in rats and mice after injury to peripheral nerve or spinal cord. The analgesic effect of sinomenine is not associated with side effects and is not reversed by the opioid receptor antagonist naloxone. Our results showed that sinomenine has a wide spectrum analgesic effect in rodent models of nociceptive, inflammatory and neuropathic pain.
Whittaker, Alexandra L.; Lymn, Kerry A.; Wallace, Georgia L.; Howarth, Gordon S.
Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis. PMID:27463799
Pozsgai, Gábor; Payrits, Maja; Sághy, Éva; Sebestyén-Bátai, Réka; Steen, Elise; Szőke, Éva; Sándor, Zoltán; Solymár, Margit; Garami, András; Orvos, Péter; Tálosi, László; Helyes, Zsuzsanna; Pintér, Erika
TRPA1 receptors are calcium-permeable ligand-gated channels expressed in primary sensory neurons and involved in inflammation and pain. Activation of these neurons might have analgesic effect. Suggested mechanism of analgesic effect mediated by TRPA1 activation is the release of somatostatin (SOM) and its action on sst4 receptors. In the present study analgesic effect of TRPA1 activation on primary sensory neurons by organic trisulfide compound dimethyl trisulfide (DMTS) presumably leading to SOM release was investigated. Opening of TRPA1 by DMTS in CHO cells was examined by patch-clamp and fluorescent Ca(2+) detection. Ca(2+) influx upon DMTS administration in trigeminal ganglion (TRG) neurons of TRPA1 receptor wild-type (WT) and knockout (KO) mice was detected by ratiometric Ca(2+) imaging. SOM release from sensory nerves of murine skin was assessed by radioimmunoassay. Analgesic effect of DMTS in mild heat injury-induced mechanical hyperalgesia was examined by dynamic plantar aesthesiometry. Regulatory role of DMTS on deep body temperature (Tb) was measured by thermocouple thermometry with respirometry and by telemetric thermometry. DMTS produced TRPA1-mediated currents and elevated [Ca(2+)]i in CHO cells. Similar data were obtained in TRG neurons. DMTS released SOM from murine sensory neurons TRPA1-dependently. DMTS exerted analgesic effect mediated by TRPA1 and sst4 receptors. DMTS-evoked hypothermia and hypokinesis were attenuated in freely-moving TRPA1 KO animals. Our study has presented original evidence regarding analgesic action of DMTS which might be due to TRPA1-mediated SOM release from sensory neurons and activation of sst4 receptors. DMTS could be a novel analgesic drug candidate. Copyright © 2017 Elsevier Inc. All rights reserved.
Whittaker, Alexandra L; Lymn, Kerry A; Wallace, Georgia L; Howarth, Gordon S
Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.
Suebsasana, Supawadee; Pongnaratorn, Panicha; Sattayasai, Jintana; Arkaravichien, Tarinee; Tiamkao, Siriporn; Aromdee, Chantana
Andrographolide (1) and 14-deoxy-11,12-didehydroandrographolide (2) are active constituents of Andrographis paniculata (Burm. f.), family Acanthaceae. A. paniculata extracts are reported to have antiviral, antipyretic, immunostimulant and anticancer activities. In this study, 1 and its 14-acetyl- (4) and 3,19-isopropylidenyl- (3) derivatives, as well as 2 and its 3,19-dipalmitoyl-derivative (5), were intraperitoneally tested for their analgesic, antipyretic, anti-inflammatory and acute toxicity effects in animal models. Analgesic effects were tested in mice using hot plate and writhing tests to distinguish the central and peripheral effects, respectively. The results showed that, at 4 mg/kg, all tested substances have significant analgesic effects, and the highest potency was seen with 3, 4 and 5. Increasing the dose of 3 and 5 to 8 mg/kg did not increase the analgesic effect. In the writhing test, 3 and 5, but not 1, showed significant results. In a baker's yeast-induced fever model, 3 and 5 significantly reduced rats' rectal temperature (p < 0.05). In a carrageenan-induced inflammation model, 1, 3 and 5 significantly reduced rats' paw volume. Doses of 3 and 5 up to 100 mg/kg did not show any serious toxic effects. From this study, 3 and 5 are the most interesting derivatives, showing much greater potency than their parent compounds. These could be further developed as analgesic, antipyretic and anti-inflammatory agents, without any serious toxicity.
Boroumand, Peyman; Zamani, Mohammad Mahdi; Saeedi, Masoumeh; Rouhbakhshfar, Omid; Hosseini Motlagh, Seyed Reza; Aarabi Moghaddam, Fatemeh
Background Tonsillectomy with or without adenoidectomy is one of the most common surgical procedures performed worldwide, especially for children. Oral honey administration following tonsillectomy in pediatric cases may reduce the need for analgesics via relieving postoperative pain. Objectives The aim of this study was to evaluate the effects of honey on the incidence and severity of postoperative pain in patients undergoing tonsillectomy. Patients and Methods A randomized, double blind, placebo controlled study was performed. One hundred and four patients, who were older than eight, and were scheduled for tonsillectomy, were divided into two equal groups, honey and placebo. Standardized general anesthesia, and postoperative usual analgesic, and antibiotic regimen were administrated for all patients. Acetaminophen plus honey for the honey group, and acetaminophen plus placebo for the placebo group were given daily. They began to receive honey or placebo when the patients established oral intake. Results The difference between acetaminophen and acetaminophen plus honey groups was statistically significant both for visual analogue scale (VAS), and number of painkillers taken within the first three postoperative days. The consumption of painkillers differed significantly in every five postoperative days. No significant difference was found between groups regarding the number of awaking at night. Conclusions Postoperative honey administration reduces postoperative pain and analgesic requirements in patients after tonsillectomy. As the side effects of honey appear to be negligible, consideration of its routine usage seems to be beneficial along with routine analgesics. PMID:24223362
A randomised, five-parallel-group, placebo-controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single-tablet combination of ibuprofen/paracetamol for postoperative dental pain.
Daniels, Stephen E; Goulder, Michael A; Aspley, Sue; Reader, Sandie
Combination analgesia is often recommended for the relief of severe pain. This was a double-blind, 5-arm, parallel-group, placebo-controlled, randomised, single-dose study designed to compare the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol with that of an ibuprofen/codeine combination, and a paracetamol/codeine combination, using the dental impaction pain model. Subjects with at least 3 impacted third molars and experiencing moderate to severe postoperative pain were randomised to receive: 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg; 2 tablets of ibuprofen 200 mg/codeine 12.8mg; 2 tablets of paracetamol 500mg/codeine 15mg; or placebo. Results for the primary endpoint, the sum of the mean scores of pain relief combined with pain intensity differences over 12hours, demonstrated that 1 and 2 tablets of the single-tablet combination of ibuprofen/paracetamol were statistically significantly more efficacious than 2 tablets of placebo (P<0.0001) and paracetamol/codeine (P⩽0.0001); furthermore, 2 tablets offered significantly superior pain relief to ibuprofen/codeine (P=0.0001), and 1 tablet was found noninferior to this combination. Adverse events were uncommon during this study and treatment emergent adverse events were statistically significantly less frequent in the groups taking the ibuprofen/paracetamol combination compared with codeine combinations. In conclusion, 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg provided highly effective analgesia that was comparable with, or superior to, other combination analgesics currently indicated for strong pain. A single-tablet combination of ibuprofen 200mg/paracetamol 500mg provides highly effective analgesia, comparable or superior to other combination analgesics indicated for strong pain. Copyright © 2011. Published by Elsevier B.V.
van den Nieuwenhuyzen, M C; Janss, R A; Brand, R; van Kleef, J W
To determine how postoperative analgesia care is managed in the Netherlands. Descriptive study (questionnaire). Departments of anaesthesiology in all 168 Dutch hospitals. Questionnaires were sent inquiring about postoperative pain therapies and their complications, the organisation and management of postoperative analgesic care, the importance of effective pain control, factors of influence on patient's assessment of pain and the management of the quality of postoperative analgesia. The questionnaires of 73% (n = 122) of the hospitals were suitable for analysis. Locoregional analgesic techniques are used, but intermittent intramuscular administration of an opioid is still the analgesic therapy of choice in the postoperative period. 89% of the interviewed anaesthesiologists assess the average intensity of postoperative pain as moderate or severe, and more than half of the interviewed anaesthesiologists answered that effective postoperative pain management is of substantial influence on the postoperative recovery of the patient. It is essential to improve postoperative pain control in the Netherlands. Frequent assessments and precise documentation of the intensity of pain and pain relief, on which further therapy can be based, might be a first step in improving postoperative pain control. Optimal postoperative pain management requires the input of equipment and staff.
Hultin, M; Olander, K J
In a double-blind comparison with placebo in 60 patients suffering from post-operative pain following the surgical removal of a third molar in the lower jaw, statistical analyses showed that Voltaren (diclofenac sodium) in a single dose of 50 mg had a significantly greater analgesic effect than placebo. The technique to be used for studies with analgesic drugs is briefly discussed.
Park, Hyun; Kim, Eun-Jin; Han, Jaehee; Han, Jongwoo
TWIK-related K+ channel-2 (TREK-2) and TWIK-related spinal cord K+ (TRESK) channel are members of two-pore domain K+ channel family. They are well expressed and help to set the resting membrane potential in sensory neurons. Modulation of TREK-2 and TRESK channels are involved in the pathogenesis of pain, and specifi c activators of TREK-2 and TRESK may be benefi cial for the treatment of pain symptoms. However, the effect of commonly used analgesics on TREK-2 and TRESK channels are not known. Here, we investigated the effect of analgesics on TREK-2 and TRESK channels. The effects of analgesics were examined in HEK cells transfected with TREK-2 or TRESK. Amitriptyline, citalopram, escitalopram, and fluoxetine significantly inhibited TREK-2 and TRESK currents in HEK cells (p<0.05, n=10). Acetaminophen, ibuprofen, nabumetone, and bupropion inhibited TRESK, but had no effect on TREK-2. These results show that all analgesics tested in this study inhibit TRESK activity. Further study is needed to identify the mechanisms by which the analgesics modulate TREK-2 and TRESK differently. PMID:27382354
Devaux, C.; Schoepffler, P.; Gauthier-Lafaye, J. P.
1 Mixed agonist-antagonist analgesics have analgesic action but also possess a range of side-effects. 2 Narcotic antagonists do not reverse the non-specific effects of opiates. 3 Under certain circumstances the effects of agonists and mixed agonist-antagonists can be additive. 4 Chronic dosage of mixed agonist-antagonists leads to a lower level of dependence than that observed with the standard narcotics. 5 Mixed agonist-antagonists may not antagonize the respiratory effects of narcotics and may result in potentiation of such depression. PMID:465294
Malmstrom, Kerstin; Ang, Jennifer; Fricke, James R; Shingo, Sumiko; Reicin, Alise
To compare the analgesic effect of single doses of etoricoxib 120 mg, oxycodone/ acetaminophen 10 mg/650 mg and codeine/ acetaminophen 60 mg/600 mg in acute pain using the dental impaction model. In this randomized, double-blind, placebo-controlled, parallel-group study, patients reported pain intensity and pain relief (16 times) and global scores (twice) during a 24-h period. The primary endpoint was the overall analgesic effect, total pain relief over 6 h (TOPAR6). Other endpoints were patient global evaluation, time to onset (2-stopwatch method), duration of analgesic effect (median time to and amount of rescue medication use). Tolerability was evaluated by overall and opioid-related (nausea and vomiting) adverse experiences. 302 patients (mean age 23; 63% women; 63 % White) were randomized to etoricoxib 120 mg, oxycodone/acetaminophen 10 mg/650 mg, codeine/acetaminophen 60 mg/600 mg, and placebo (2:2:1:1). Etoricoxib demonstrated significantly greater overall analgesic efficacy (TOPAR6) (13.2 units) versus oxycodone/acetaminophen (10.2 units); and codeine/acetaminophen (6.0 units); p < 0.001 for all. All active treatments were superior to placebo. Median time to onset was significantly (p < 0.001) shorter for oxycodone/acetaminophen (20 min) and numerically but not significantly shorter (p = 0.259) for codeine/acetaminophen (26 min) compared with etoricoxib (40 min). Etoricoxib (24 h) had a significantly longer lasting analgesic effect than oxycodone/acetaminophen (5.3 h), codeine/acetaminophen (2.7 h), and placebo (1.7 h) (p < 0.001 for all). Etoricoxib patients experienced fewer clinical adverse experiences than patients on oxycodone/acetaminophen and codeine/acetaminophen, specifically, significantly (p < 0.05) fewer episodes of nausea. Etoricoxib 120 mg provided superior overall analgesic effect with a smaller percentage of patients experiencing nausea versus both oxycodone/acetaminophen 10 mg/650 mg and codeine/acetaminophen 60 mg/600 mg.
Navarro, Suelen A; Serafim, Karla G G; Mizokami, Sandra S; Hohmann, Miriam S N; Casagrande, Rubia; Verri, Waldiceu A
Piracetam is a prototype of nootropic drugs used to improve cognitive impairment. However, recent studies suggest that piracetam can have analgesic and anti-inflammatory effects. Inflammatory pain is the result of a process that depends on neutrophil migration, cytokines and prostanoids release and oxidative stress. We analyze whether piracetam has anti-nociceptive effects and its mechanisms. Per oral pretreatment with piracetam reduced in a dose-dependent manner the overt pain-like behavior induced by acetic acid, phenyl-p-benzoquinone, formalin and complete Freund's adjuvant. Piracetam also diminished carrageenin-induced mechanical and thermal hyperalgesia, myeloperoxidase activity, and TNF-α-induced mechanical hyperalgesia. Piracetam presented analgesic effects as post-treatment and local paw treatment. The analgesic mechanisms of piracetam were related to inhibition of carrageenin- and TNF-α-induced production of IL-1β as well as prevention of carrageenin-induced decrease of reduced glutathione, ferric reducing ability and free radical scavenging ability in the paw. These results demonstrate that piracetam presents analgesic activity upon a variety of inflammatory stimuli by a mechanism dependent on inhibition of cytokine production and oxidative stress. Considering its safety and clinical use for cognitive function, it is possible that piracetam represents a novel perspective of analgesic. Copyright © 2013 Elsevier Inc. All rights reserved.
Karandikar, Yogita S.; Belsare, Peeyush; Panditrao, Aditi
Objective: The underlying mechanisms for the analgesic action of paracetamol (PCT) are still under considerable debate. It has been recently proposed that PCT may act by modulating the Serotonin system. This study was conducted to verify the influence of Serotonin modulating drugs (buspirone, ondansetron, and fluoxetine) on the analgesic effect of PCT. Materials and Methods: Thirty adult albino mice were assigned to five groups: Normal saline, PCT, fluoxetine selective serotonin reuptake inhibitor (SSRI) + PCT, buspirone (5-HT1A Agonist) + PCT, and ondansetron (5HT3 antagonist) + PCT. Hot-plate and formalin test were used to determine pain threshold, tests being conducted 60 min after the last treatment. Statistical analysis was done using analysis of variance followed by Dunnet's test. Results: Coadministration of buspirone with PCT attenuated the antinociceptive activity of PCT (P < 0.001), whereas fluoxetine + PCT increased pain threshold in the hot-plate and formalin test (P = 0.0046). Analgesic effect of PCT was not affected by ondansetron in formalin models. It attenuated analgesic action of PCT in hot-plate test (P = 0.0137). Conclusion: The results suggest that 5-HT1 receptors could also be responsible for the analgesic effect of PCT. Also, higher analgesia is produced by co-administration of SSRI (fluoxetine) + PCT. PMID:27298498
Alexa, Teodora; Marza, Aurelia; Voloseniuc, Tudor; Tamba, Bogdan
Chronic pain is managed mostly by the daily administration of analgesics. Tramadol is one of the most commonly used drugs, marketed in combination with coanalgesics for enhanced effect. Trace elements are frequent ingredients in dietary supplements and may enhance tramadol's analgesic effect either through synergic mechanisms or through analgesic effects of their own. Swiss Weber male mice were divided into nine groups and were treated with a combination of the trace elements Mg, Mn, and Zn in three different doses and a fixed dose of tramadol. Two groups served as positive (tramadol alone) and negative (saline) controls. Nociceptive assessment by tail-flick (TF) and hot-plate (HP) tests was performed at baseline and at 15, 30, 45, and 60 min after intraperitoneal administration. Response latencies were recorded and compared with the aid of ANOVA testing. All three trace elements enhanced tramadol's analgesic effect, as assessed by TF and HP test latencies. Coadministration of these trace elements led to an increase of approximately 30% in the average pain inhibition compared with the tramadol-alone group. The most effective doses were 0.6 mg/kg b.w. for Zn, 75 mg/kg b.w. for Mg, and 7.2 mg/kg b.w. for Mn. Associating trace elements such as Zn, Mg, and Mn with the standard administration of tramadol increases the drug's analgesic effect, most likely a consequence of their synergic action. These findings impact current analgesic treatment because the addition of these trace elements may reduce the tramadol dose required to obtain analgesia. © 2015 Wiley Periodicals, Inc.
Erden, Sevilay; Demir, Sevil Güler; Kanatlı, Ulunay; Danacı, Fatma; Carboğa, Banu
Pain assessment has a key role in relief of the postoperative pain. In this study, we aimed to examine the effect of the Standard Pain Assessment Protocol (SPAP), which we developed based on acute pain guidelines, on pain level, and analgesic consumption. The study population consisted of a total of 101 patients who had arthroscopic shoulder surgery. The routine pain assessment was administered to the control group, while the SPAP was administered to the study group. The routine pain therapy of the clinic was administered to the subjects from both groups based on the pain assessment. Throughout the study, pain was assessed nearly two times more in the study group (p<0.001) and the mean pain levels were lower at 8th-11th hours in the study group (p<0.001). Pain assessment was not performed after 12th hour despite the severe pain in the control group, and, therefore, analgesia was administered at irregular intervals or was not administered at all. However, the hours of analgesic administration were found to be more regular according to the pain levels of the patients in the study group. In conclusion, the SPAP reduced the pain level by providing regular analgesia when used in combination with regular pain assessment. This article highlights the appropriate assessment for patients with surgical pain. In majority of literature on the subject, the authors emphasize the importance of Standard Pain Assessment Protocol to provide adequate pain relief. Copyright © 2016 Elsevier Inc. All rights reserved.
DeRossi, R; Junqueira, A L; Beretta, M P
The objective of the study was to determine the analgesic and systemic effects of subarachnoid administration of xylazine hydrochloride (XY), lidocaine hydrochloride (LI) and their combination (XYLI) in goats. Six healthy goats were used in a prospective randomised study. Three treatments were administered to each goat, with 1-week intervals between each treatment. Treatments consisted of 0.1 mg/kg xylazine, 2.5 mg/kg lidocaine and a combination of xylazine 0.05 (mg/kg) and lidocaine (1.25 mg/kg). Analgesia, ataxic, sedative, cardiovascular and respiratory effects, and rectal temperature were evaluated before (baseline) and at 5, 10, 15, and 30 min after subarachnoid injection, and then at 30-min intervals until loss of analgesia occurred. Lidocaine induced analgesia in 3.1 +/- 1 min (mean +/- SD), which lasted for 66 +/- 31 min. Heart and respiratory rates and blood pressure remained unchanged after lidocaine-induced analgesia. Xylazine induced analgesia in 9.5 +/- 2.6 min and xylazine-lidocaine in 3.2 +/- 1.2 min. Xylazine-lidocaine-induced analgesia lasted longer (178.3 +/- 37 min) than that induced by xylazine (88.3 +/- 15 min). The XYLI treatment induced prolonged motor blocking (115 min), more than the XY (80 min) and LI (90 min) treatments. Both xylazine and xylazine-lidocaine caused significant decreases in the heart and respiratory rates, but not in blood pressure. The combination of xylazine (0.05 mg/kg) and lidocaine (1.25 mg/kg) can be administered subarachnoidally (between last lumbar vertebra and 1st sacral vertebra) to produce prolonged (> 2.5 h) analgesia of the tail, perineum, hind limbs, flanks and caudodorsal rib areas in goats. Despite the prolonged analgesia, using this combination is desirable for relieving postoperative pain, but it may be a disadvantage due to a motor block when dealing with goats.
Wang, Jingjie; Dai, Dongyan; Qiu, Qianqian; Deng, Xin; Lin, Haiyan; Qian, Hai; Huang, Wenlong
Inflammatory and pain are major areas for drug discovery. Current analgesic drugs often cause a number of side-effects. In the present study, we modified carboxylic acid group of ibuprofen, one of non-steroidal anti-inflammatory drugs, based on the common structure of transient receptor potential vanilloid type 1 antagonists which are considered as new candidates for analgesic drugs, and synthesized several derivatives of ibuprofen. Comprehensive evaluations of the pharmacological properties of these compounds were investigated. Compound 17 showed weak cyclooxygenase inhibition and exhibited strong transient receptor potential vanilloid type 1 antagonistic activity. It was found to be capable of blocking noxious thermal nociception and capsaicin-induced nociception in mice. Besides, 17 showed less ulcerogenic action than ibuprofen did and had no hyperthermia side-effect compared with common transient receptor potential vanilloid type 1 antagonists. Therefore, it suggested that 17 could be used as a safe alternative analgesic candidate for pain treatment.
Stiglitz, D K; Amaratunge, L N; Konstantatos, A H; Lindholm, D E
Preventive analgesia is defined as the persistence of the analgesic effects of a drug beyond the clinical activity of the drug. The N-methyl D-aspartate receptor plays a critical role in the sensitisation of pain pathways induced by injury. Nitrous oxide inhibits excitatory N-methyl D-aspartate sensitive glutamate receptors. The objective of our study was to test the efficacy of nitrous oxide as a preventive analgesic. We conducted a retrospective analysis of data from a subset of patients (n = 100) randomly selected from a previous major multicentre randomised controlled trial on nitrous oxide (ENIGMA trial). Data analysed included postoperative analgesic requirements, pain scores and duration of patient-controlled analgesia during the first 72 postoperative hours. There was no significant difference in postoperative oral morphine equivalent usage (nitrous group 248 mg, no nitrous group 289 mg, mean difference -43 mg, 95% confidence interval 141 to 54 mg). However, patients who received nitrous oxide had a shorter duration of patient-controlled analgesia use (nitrous group 35 hours, no nitrous group 51 hours, mean difference -16 hours, 95% confidence interval -29 to -2 hours, P = 0.022). There was no difference in pain scores between the groups. The shorter patient-controlled analgesia duration in the nitrous oxide group suggests that intraoperative nitrous oxide may have a preventive analgesic effect.
Song, Tieying; Wang, Liwen; Gu, Kunfeng; Yang, Yunliang; Yang, Lijun; Ma, Pengyu; Ma, Xiaojing; Zhao, Jianhui; Yan, Ruyv; Guan, Jiao; Wang, Chunping; Qi, Yan; Ya, Jian
Thalidomide was introduced to the market in 1957 as a sedative and antiemetic agent, and returned to the market for the treatment of myelodysplastic syndrome and multiple myeloma. There are reports and studies of thalidomide as an analgesic or analgesic adjuvant in clinic. However, the underlying mechanism is quite elusive. Many studies suggest that the analgesic effect of thalidomide may be due to its immunomodulatory and anti-inflammatory properties as it suppresses the production of tumor necrosis factor α (TNF-α) selectively. However, it is not clear whether any other mechanisms are implicated in the pain relief. In this study, we demonstrated that the peripheral vanilloid receptor 1 (TRPV1) channel was also involved in the analgesic effect of thalidomide in different cell and animal models. During the activation by its agonist capsaicin, the cation inward influx through TRPV1 channels and the whole-cell current significantly decreased after TRPV1-overexpressed HEK293 cells or dorsal root ganglion (DRG) neurons were pre-treated with thalidomide for 20 minutes. And such attenuation in the TRPV1 activity was in a dose-dependent manner of thalidomide. In an acetic acid writhing test, pre-treatment of thalidomide decreased the writhing number in the wild type mice, while it did not happen in TRPV1 knockout mice, suggesting that the TRPV1 channel was involved in the pain relief by thalidomide. Taken together, the study showed that TRPV1 channels were involved in the analgesic effects of thalidomide. Such alteration in the action of TRPV1 channels by thalidomide may help understand how thalidomide takes analgesic effect in the body in addition to its selective inhibition of TNF-α production.
Hotta, Kunihisa; Endo, Tetsuya; Taira, Koki; Sata, Naho; Inoue, Soichiro; Takeuchi, Mamoru; Seo, Norimasa; Endo, Shunsuke
A prospective, randomized, open study. The regional technique used was not blinded. A university teaching hospital. Forty-eight patients undergoing video-assisted thoracoscopic surgery (VATS) for tumor resection. Patients received either continuous extrapleural block or continuous epidural block using ropivacaine for a period of 60 hours after surgery. To evaluate postoperative pain control, the primary and secondary endpoints were the visual analog scale (VAS) on movement and the amount of rescue analgesia, respectively. There were no significant differences between the extrapleural and epidural block groups with regard to VAS at rest and during movement assessed at 4, 12, 24, 36, and 48 hours after surgery, dosage of intravenous morphine (extrapleural: 12.9 ± 11.3, epidural: 10.2 ± 6.9 mg), supplemental nonsteroidal anti-inflammatory drugs, incidence of postoperative nausea and vomiting (extrapleural: 12/20, epidural: 11/20), postoperative ambulation (extrapleural: 18 at postoperative day [POD] 1 and 20 at POD 2, epidural: 19 at POD 1 and 20 at POD 2) and hospital stay after surgery (extrapleural: 12.7 ± 6.3, epidural: 12.6 ± 4.7 days). Although this study did not show the superiority of continuous extrapleural block relative to continuous epidural in VATS patients, the results suggest that both methods provided effective analgesia with a relatively small dose of rescue morphine. Although the analgesic effects of these techniques were comparable, extrapleural block has the advantage of safety and precise placement of the catheter and can be considered an alternative to epidural block in VATS patients. Copyright © 2011. Published by Elsevier Inc.
Voogt, Lennard; de Vries, Jurryt; Meeus, Mira; Struyf, Filip; Meuffels, Duncan; Nijs, Jo
Current evidence shows that manual therapy elicits analgesic effect in different populations (healthy, pain inflicted and patients with musculoskeletal pain) when carried out at the spinal column, although the clinical significance of these effects remains unclear. Also the analgesic effects of manual therapy on peripheral joints have not been systematically reviewed. A systematic review was carried out following the PRISMA-guidelines. Manual therapy was defined as any manual induced articular motion with the aim of inducing analgesic effects. Outcome measure was pain threshold. A total of 13 randomized trials were included in the review. In 10 studies a significant effect was found. Pressure pain thresholds increased following spinal or peripheral manual techniques. In three studies both a local and widespread analgesic effect was found. No significant effect was found on thermal pain threshold. Moderate evidence indicated that manual therapy increased local pressure pain thresholds in musculoskeletal pain, immediately following the intervention. No consistent result was found on remote pressure pain threshold. No significant changes occured on thermal pain threshold values. The clinical relevance of these effects remains contradictory and therefore unclear. Copyright © 2014 Elsevier Ltd. All rights reserved.
Abdulla, Susanne; Eckhardt, Regina; Netter, Ute; Abdulla, Walied
In a randomized, double-blind trial, the synergistic action of intravenous parecoxib, metamizol or paracetamol on postoperative piritramide consumption was compared in patients recovering from total thyroidectomy during the first 24 h while evaluating pain intensity and patient satisfaction. 120 patients were randomly allocated to four patient groups treated with normal saline and/or one of non-opioid analgesics (parecoxib 40 mg twice daily, metamizol 1 g three times daily, paracetamol 1 g three times daily) in addition to piritramide using the PCA pump. Beginning in the recovery room (PACU), patients were asked every 2 h for 6 hours and afterwards once every 6 h to quantify their pain experience and patient satisfaction while piritramide consumption was recorded. Upon arrival in the PACU piritramide consumption was high and decreased thereafter significantly in all groups (P < 0.05). There were no significant differences between groups in incremental and cumulative piritramide consumption during the investigation. Also, VAS scores were high upon arrival in the PACU and dropped in all groups continuously after surgery: At 2 h and 4 h after surgery they were significantly lower in parecoxib group compared with NaCl (P < 0.01). For overall patient satisfaction, no significant differences were observed. Pain relief scores at 24 h were significantly higher in parecoxib group as compared to metamizol and paracetamol (P < 0.01). Mild PONV was observed frequently in all groups and was treated with metoclopramide. There is no clear-cut difference between the non-opioid drugs used, even though parecoxib seems to be superior in regard to VAS scores and piritramide consumption. However, the clinical significance is debatable.
Ojewole, J A O
In many parts of Africa, the leaf, stem-bark, and roots of Psidium guajava Linn. (Family: Myrtaceae) are used traditionally for the management, control, and/or treatment of an array of human disorders. In an effort to scientifically appraise some of the ethnomedical properties of P. guajava leaf, and probe its efficacy and safety, the present study was undertaken to examine the antiinflammatory and analgesic properties of the plant's leaf aqueous extract in some experimental animal paradigms. The antiinflammatory property of the aqueous leaf extract was investigated in rats, using fresh egg albumin-induced pedal (paw) edema, while the analgesic effect of the plant extract was evaluated by the "hot-plate" and "acetic acid" test models of pain in mice. Diclofenac (100 mg/kg, i.p.) and morphine (10 mg/kg, i.p.) were used respectively as standard, reference antiinflammatory and analgesic agents for comparison. P. guajava leaf aqueous extract (PGE, 50-800 mg/kg, i.p.) produced dose-dependent and significant (p < 0.05-0.001) inhibition of fresh egg albumin-induced acute inflammation (edema) in rats. The plant extract (PGE, 50-800 mg/kg, i.p.) also produced dose-dependent and significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain in mice. The numerous tannins, polyphenolic compounds, flavonoids, ellagic acid, triterpenoids, guiajaverin, quercetin, and other chemical compounds present in the plant are speculated to account for the observed antiinflammatory and analgesic effects of the plant's leaf extract. In summary, the findings of this experimental animal study indicate that the leaf aqueous extract of P. guajava possesses analgesic and antiinflammatory properties, and thus lend pharmacological credence to the suggested ethnomedical, folkloric uses of the plant in the management and/or control of painful, arthritic and other inflammatory conditions in some rural communities of Africa. (c) 2006 Prous Science. All rights
Wang, Na; Wang, Lei; Gao, Yang; Zhou, Honglan
Objective: To assess whether preoperative pentazocine can reduce intraoperative hemodynamic changes and postoperative pain. Methods: Fifty patients undergoing laparoscopic cholecystectomy were randomized into two groups. Group P received intravenous 0.5 mg/kg pentazocine 10 min before surgery, and Group C received normal saline as a placebo. A standardized general anesthesia was conducted in all patients. Mean blood pressure (MBP), heart rate (HR), and visual analog scale (VAS) scores at various time points were recorded. The tramadol consumption during the study period was recorded. Results: Group P had lower VAS scores at two, four, and eight hours postoperatively compared with Group C. MBP and HR rose significantly because of pneumoperitoneum within Group C, and no significant changes were detected in MBP and HR within Group P. Tramadol doses given were statistically fewer in Group P. Conclusion: Preoperative intravenous pentazocine can decrease intraoperative hemodynamic changes and postoperative pain. PMID:28168126
Merema, Danielle K; Schoenrock, Emily K; Le Boedec, Kevin; McMichael, Maureen A
OBJECTIVE To determine the effects of a transdermal lidocaine patch (TLP) on indicators of postoperative pain in healthy dogs following ovariohysterectomy. DESIGN Randomized, blinded controlled trial. ANIMALS 40 healthy shelter-owned female dogs admitted to a student surgery program for ovariohysterectomy. PROCEDURES Dogs were randomly assigned to receive after ovariohysterectomy a 5-cm-wide strip of TLP applied topically on both sides of the incision, for the full length of the incision and a wound dressing (n = 19) or a placebo patch (nonmedicated wound dressing; 21). All dogs underwent midline ovariohysterectomy. Immediately afterward, dogs received 2 IM morphine injections, carprofen (SC, q 12 h for 2 days), and the assigned patch (left in place for 18 hours). Postoperative comfort was evaluated by use of the short form of the Glasgow Composite Measures Pain Scale and serum cortisol concentrations measured prior to premedication and 1, 2, 4, 6, 8, 10, and 18 hours after surgery. RESULTS No significant difference in pain scores or serum cortisol concentrations was identified between dogs that received the TLP and dogs that received a placebo patch after ovariohysterectomy. CONCLUSIONS AND CLINICAL RELEVANCE The TLP provided no additional analgesic benefit to dogs treated concurrently with recommended doses of morphine and carprofen following ovariohysterectomy. Additional studies are needed to investigate whether similar results might be achieved in dogs treated concurrently with other analgesics. (J Am Vet Med Assoc 2017;250:1140-1147).
Campagnol, Daniela; Teixeira-Neto, Francisco J; Monteiro, Eduardo R; Restitutti, Flávia; Minto, Bruno W
To compare the effect of intraperitoneal (IP) or incisional (INC) bupivacaine on pain and the analgesic requirement after ovariohysterectomy in dogs. Prospective, randomized clinical study. Thirty female dogs undergoing ovariohysterectomy (OHE). Dogs admitted for elective OHE were anesthetized with acepromazine, butorphanol, thiopental and halothane. Animals were randomly assigned to one of three groups (n = 10 per group). The treatments consisted of preincisional infiltration with saline solution (NaCl 0.9%) or bupivacaine with epinephrine and/or IP administration of the same solutions, as follows: INC and IP 0.9% NaCl (control group); INC 0.9% NaCl and IP bupivacaine (5 mg kg(-1), IP group); INC bupivacaine (1 mg kg(-1)) and IP 0.9% NaCl (INC group). Postoperative pain was evaluated by a blinded observer for 24 hours after extubation by means of a visual analog scale (VAS) and a numeric rating scale (NRS). Rescue analgesia (morphine, 0.5 mg kg(-1) , IM) was administered if the VAS was >5/10 or the NRS >10/29. At 1 hour after anesthesia, VAS pain scores were [medians (interquartile range)]: 6.4 (3.1-7.9), 0.3 (0.0-2.6) and 0.0 (0.0-7.0) in control, IP and INC groups, respectively. VAS pain scores were lower in the IP compared to the control group. Over the first 24 hours, rescue analgesia was administered to 7/10, 5/10 and 3/10 dogs of the control, INC and IP groups, respectively. Total number of dogs given rescue analgesia over the first 24 hours did not differ significantly among groups. Intraperitoneal bupivacaine resulted in lower pain scores during the first hour of the postoperative period and there was a trend towards a decreased need for rescue analgesia after OHE in dogs. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.
Shimoyama, Megumi; Szeto, Hazel H; Schiller, Peter W; Tagaito, Yugo; Tokairin, Hideyuki; Eun, Chong moon; Shimoyama, Naohito
H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA), a highly selective micro-opioid peptide, is potently analgesic after systemic and intrathecal administration but is less potent given intracerebroventricularly. This study was performed to further characterize the analgesic effects of [Dmt(1)]DALDA. We compared the effects of [Dmt(1)]DALDA and morphine after systemic administration in two different acute pain tests, the tail flick test and the paw withdrawal test, and examined how antagonizing the spinal opioid actions would affect their analgesic effects. [Dmt(1)]DALDA was markedly more potent in the tail flick test than in the hot plate test, while the potencies of morphine were similar in the two tests. Intrathecal naloxone completely blocked the effect of systemic [Dmt(1)]DALDA in the tail flick test, while it only partially blocked the effect of morphine. At higher doses that produced analgesia in the hot plate test, the effect of [Dmt(1)]DALDA in this test was only partially blocked by naloxone. Systemic [Dmt(1)]DALDA has a unique analgesic property clearly different from that of morphine and it has a propensity to produce spinal analgesia.
Sebastian, Bon; Nelamangala, Kiran; Krishnamurthy, Dinesh
Introduction Conquering postoperative pain which has significant impact on the surgery outcome can be challenging for the clinicians. Pregabalin is a GABA analogue used for various neuropathic pain syndromes. Very few studies are there with the use of pregabalin as a preemptive analgesic for orthopedic surgeries. Aim To compare pregabalin 150 mg with placebo for postoperative pain control in patients undergoing elective lower limb orthopedic surgeries under spinal anaesthesia and to assess any side effects. Materials and Methods A randomized double blinded prospective study was undertaken. Ninety patients with ASA physical status I, II, aged between 18–50 years were enrolled in the study. One hour prior to spinal anaesthesia Group C - received colour matched empty capsules, Group P – received 150mg of oral pregabalin. Spinal anaesthesia was administered in sitting position in L3-L4 space with Inj. Bupivacaine heavy (0.5%) at a dose of 0.3mg/kg body weight with 20 mg being the maximum dose using 25 gauge spinal needle. Rescue analgesia was provided with using Inj. Diclofenac 1.5 mg/kg intramuscular. Results Time for rescue analgesia (VAS score >3) was significantly increased in Group P than in Group C. The total dose of diclofenac required in the 24 hour postoperative period was significantly lower in Group P than in Group C. The sedation scores and patient satisfaction scores were also more in Group P than in Group C. Conclusion Preemptive pregabalin in an oral dose of 150 mg offers good postoperative analgesia in lower limb orthopedic surgeries under spinal anaesthesia. PMID:27630927
Sebastian, Bon; Talikoti, Anand Tippanna; Nelamangala, Kiran; Krishnamurthy, Dinesh
Conquering postoperative pain which has significant impact on the surgery outcome can be challenging for the clinicians. Pregabalin is a GABA analogue used for various neuropathic pain syndromes. Very few studies are there with the use of pregabalin as a preemptive analgesic for orthopedic surgeries. To compare pregabalin 150 mg with placebo for postoperative pain control in patients undergoing elective lower limb orthopedic surgeries under spinal anaesthesia and to assess any side effects. A randomized double blinded prospective study was undertaken. Ninety patients with ASA physical status I, II, aged between 18-50 years were enrolled in the study. One hour prior to spinal anaesthesia Group C - received colour matched empty capsules, Group P - received 150mg of oral pregabalin. Spinal anaesthesia was administered in sitting position in L3-L4 space with Inj. Bupivacaine heavy (0.5%) at a dose of 0.3mg/kg body weight with 20 mg being the maximum dose using 25 gauge spinal needle. Rescue analgesia was provided with using Inj. Diclofenac 1.5 mg/kg intramuscular. Time for rescue analgesia (VAS score >3) was significantly increased in Group P than in Group C. The total dose of diclofenac required in the 24 hour postoperative period was significantly lower in Group P than in Group C. The sedation scores and patient satisfaction scores were also more in Group P than in Group C. Preemptive pregabalin in an oral dose of 150 mg offers good postoperative analgesia in lower limb orthopedic surgeries under spinal anaesthesia.
Berntzen, Dagfinn; Gotestam, K. Gunnar
Compared the effects of fixed-interval and on-demand administration of analgesic medications in chronic pain patients. A fixed-interval analgesic schedule was found more effective than an on-demand schedule in reducing subjective pain and elevating mood. No differences were found between the two conditions on measures of physical activity.…
Berntzen, Dagfinn; Gotestam, K. Gunnar
Compared the effects of fixed-interval and on-demand administration of analgesic medications in chronic pain patients. A fixed-interval analgesic schedule was found more effective than an on-demand schedule in reducing subjective pain and elevating mood. No differences were found between the two conditions on measures of physical activity.…
Cooper, Ziva D; Sullivan, Maria A; Vosburg, Suzanne K; Manubay, Jeanne M; Haney, Margaret; Foltin, Richard W; Evans, Suzette M; Kowalczyk, William J; Saccone, Phillip A; Comer, Sandra D
Tolerance to the analgesic effects of opioids has been demonstrated in laboratory animals after repeated drug administration, yet this effect has been studied less frequently under controlled laboratory conditions in humans. This within-subject, double-blind, placebo-controlled study was designed to determine if tolerance developed to the analgesic, subjective, and physiological effects of the commonly prescribed opioid oxycodone when it was administered daily for 5 days. The effects of oxycodone’s (0, 5, and 20 mg/70 kg, p.o.) were compared, using a within-session cumulative dosing procedure, on the 1st and 5th days of the ‘daily’ dosing phase to assess for tolerance; active oxycodone was administered on the 2nd-4th days of the daily dosing phase. Changes in the effects of oxycodone were also compared when the medication was only administered on the 1st and 5th day of a 5-day ‘intermittent’ dosing phase; placebo medication was administered on the 2nd–4th days of the intermittent dosing phase. A 9-day ‘washout’ period occurred between phases when no medication was administered. Healthy volunteers (N=10) with no history of drug dependence or current drug use participated in this outpatient study. Analgesia was assessed using the Cold-Pressor Test (CPT), pain and drug effects were measured using a variety of questionnaires, and pupil diameter was monitored as an index of physiological effects. When administered daily, no differences were observed in oxycodone-induced analgesia between the 1st and 5th days, but tolerance did develop to some of the positive subjective effects of oxycodone. In contrast, oxycodone-induced analgesia and participant ratings of some positive subjective drug effects were greater on the 5th day compared to the 1st day of the intermittent dosing phase. No differences in the miotic effects of oxycodone between the 1st and 5th days of either dosing phase were detected. Though obtained under limited experimental conditions, these
Mammoto, Takeo; Fujie, Keiko; Mamizuka, Naotaka; Taguchi, Noriko; Hirano, Atsushi; Yamazaki, Masashi; Ueno, Satoshi; Ma, Enbo; Hashimoto, Koichi
Multimodal analgesia is achieved by combining different analgesics and different methods of analgesic administration, synergistically providing superior pain relief when compared with conventional analgesia. Multimodal analgesia can also result in reductions in the side effects and complications of analgesia, thereby improving patient safety. Preventive analgesia, treatment before initiation of the surgical procedure, has a potential to be more effective in reducing pain sensitization than treatment initiated after surgery. Multimodal analgesia that includes prophylactic administration of selective cyclooxygenase-2 (COX-2) inhibitors can improve postoperative pain and reduce opioid analgesic consumption after total knee arthroplasty (TKA). However COX-2 inhibitors are not approved for use as preventive analgesia in Japan. Thus, assessing the effectiveness of COX-2 inhibitors during the early postoperative period is important to establish clinical practice guidelines in Japan. This study was designed to examine the effects of celecoxib administration immediately after surgery, in addition to multimodal analgesia, on postoperative pain management after TKA. This randomized, prospective, open-label controlled study will include 120 patients undergoing unilateral TKA. All patients will routinely receive single injections of femoral and sciatic nerve blocks, along with postoperative patient-controlled analgesia (PCA) with fentanyl. Patients will be randomly assigned to receive or not receive immediate postoperative administration of celecoxib. The primary outcome is a visual analog scale (VAS) pain score the second day after surgery. Secondary outcomes include opioid consumption, VAS pain score for 7 days after surgery, range of knee motion, evaluation of sleep quality, overall evaluations by patients and physicians, rates of postoperative nausea and vomiting, and consumption of rescue analgesics. The objective of this study is to evaluate the effects of celecoxib
De Capraris, A; Cinnella, G; Marolla, A; Salatto, P; Da Lima, S; Vetuschi, P; Consoletti, L; Gesualdo, L; Dambrosio, M
The single-nucleotide-polymorphism (SNP) 118A>G in the micro-1 opioid receptor gene (OPRM1) is associated with a decrease in the analgesic effects of opioids. The aim of this study is to assess whether 118A >G polymorphism could influence the analgesic response to opioid-based postoperative pain (POP) therapy. The study consisted of two parts: section alpha, observational, included 199 subjects undergoing scheduled surgical procedures with pain management standardized on surgery invasiveness and on expected level of postoperative pain; section beta, randomized, included 41 women undergoing scheduled caesarean delivery with continuous intra-operative epidural anesthesia and post-operative analgesia (CEA). In both sections, POP was measured over 48 h (T6h-T24h-T48h) by the visual analogue scale (VAS). In section beta we also tested the responsiveness of hypothalamic-pituitary-adrenal axis (HPA) expressed by cortisol levels. In section alpha, with cluster analysis, subjects were analyzed according to their genotype: a group (no. 1) of 34 patients reporting VAS score >3 at every time lapse was identified and included only A118G carriers, while wild-type (A118A - absence of 118A>G polymorphism) patients were unevenly distributed between those with cluster no. 2 (VAS score <3 at every study steps) and those with cluster no. 3 (VAS score progressively reducing from T6h). In section beta, A118G carriers receiving epidural sufentanil had the lowest VAS scores at T24h; also in these patients, cortisol levels remained more stable, with a mild decrease at T6h. This study shows that the OPRM1 118A>G polymorphism affects postoperative pain response in heterozygous patients: they have a different postoperative pain response than patients with wild-type genes, which may affect the efficacy of the analgesic therapy.
O'Neil, Christine K; Hanlon, Joseph T; Marcum, Zachary A
Osteoarthritis (OA) is the most common cause of disability in older adults, and although analgesic use can be helpful, it can also result in adverse drug events. To review the recent literature to describe potential adverse drug events associated with analgesics commonly used by older adults with OA. To identify articles for this review, a systematic search of the English-language literature from January 2001 to June 2012 was conducted using PubMed, MEDLINE, EBSCO, and the Cochrane Database of Systematic Reviews for publications related to the medical management of OA. Search terms used were "analgesics," "acetaminophen," "nonsteroidal anti-inflammatory drugs" (NSAIDs), "opioids," "pharmacokinetics," "pharmacodynamics," and "adverse drug events." The search was restricted to those articles that concerned humans aged ≥65 years. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional articles. From these, the authors identified those studies that examined analgesic use in older adults. There are limited data to suggest that non-frail elders are more likely than their younger counterparts to develop acetaminophen-induced hepatotoxicity. However, decreased hepatic phase II metabolism in frail elders may result in increased risk of hepatotoxicity. It is now well established that older adults are at higher risk of NSAID-induced gastrointestinal toxicity and renal insufficiency. Insofar as opioids, the data that suggest an increased risk of falls, fractures, or delirium need to be tempered by the potential risk of inadequately treating severe chronic OA-related pain. Acetaminophen is the mainstay frontline analgesic for treating OA-related pain in older adults. NSAIDs should be limited to short-term use only, and for moderate to severe OA-related pain, opioids may be preferable in individuals without substance abuse or dependence issues. Copyright © 2012
Rademaker, B M; Kalkman, C J; Odoom, J A; de Wit, L; Ringers, J
We have compared the efficacy of 0.9% NaCl 20 ml (n = 15), 0.25% bupivacaine 20 ml (n = 15) and 0.5% lignocaine 20 ml (n = 15), administered i.p., in reducing postoperative pain and opioid requirements, and modifying the metabolic response to surgery and postoperative lung function after laparoscopic cholecystectomy. There were no differences in postoperative pain scores (visual analogue scale and verbal rating scale) between the three groups in the first 4 h after operation and in analgesic requirements during the first 24 h. In all groups, forced vital capacity, peak expiratory flow and forced expiratory volume in 1 s decreased 2 h after surgery (P < 0.001). Ventilatory values recovered only partially in the first 2 days after operation (P < 0.05), with no significant differences between groups. Plasma concentrations of glucose and cortisol increased after surgery (P < 0.05). Cortisol concentrations returned to baseline 48 h after operation. There were no significant differences between the groups in any measured variable. These data suggest that the administration of 20 ml of local anaesthetics i.p. is not effective in reducing postoperative pain, improving lung function, or attenuating the metabolic endocrine response after laparoscopic cholecystectomy.
Miech, Richard; Bohnert, Amy; Heard, Kennon; Boardman, Jason
Purpose Nonmedical use of prescription pain drugs (hereafter ‘analgesics’) has increased substantially in recent years. It is not known whether today’s youth are disproportionately driving this increase or, instead, the trend is a general one that has affected cohorts of all ages similarly. To address this question we present the first age-period-cohort analysis of nonmedical use of analgesics. Methods Data come from the National Survey on Drug Use and Health, a series of annual, nationally-representative, cross-sectional surveys of the U.S. civilian, non-institutionalized population. The analysis focuses on the years 1985 to 2009 and uses the recently developed ‘intrinsic estimator’ algorithm to disentangle age-period-cohort effects. Results Substantial increases in the prevalence of nonmedical analgesics use have occurred across all cohorts and ages in recent years, but this increase is significantly amplified among today’s adolescents. The odds of past-year, nonmedical analgesics use for today’s youngest cohort (born 1980–1994) are higher than would be expected on the basis of their age and broad, historical period influences that have increased use across people of all ages and cohorts. The independent influence of cohort on past-year, nonmedical analgesics use is about 40% higher for today’s youth cohort than any of the cohorts that came before them. This finding is present among men, women, non-Hispanic whites, non-Hispanic blacks, and Hispanics. Conclusions Although nonmedical use of analgesics is evident among all ages, cohorts, and periods, today’s younger cohorts warrant special attention for substance abuse policies and interventions targeted at reversing the increase in nonmedical analgesics use. PMID:23260832
Simonse, Eva; Mulder, Paul G H; van Beek, Ron H T
The purpose of this trial was to investigate whether breast milk (either breastfed or bottle-fed) has a better analgesic effect than sucrose in newborns born at a postmenstrual age between 32 and 37 weeks. We conducted a randomized controlled trial at a secondary care neonatal unit in the Netherlands on 71 preterm neonates (postmenstrual age at birth 32-37 weeks), undergoing heel lance with an automated piercing device. Newborns were randomly assigned to breast milk (either breastfed or bottle-fed) administered during heel lance or oral sucrose administered before heel lance. We assessed the Premature Infant Pain Profile (PIPP) score (range, 0-21) to investigate whether there was a difference in pain score between neonates receiving breast milk and those receiving sucrose solution. There was no significant difference in mean PIPP score between neonates receiving breast milk (6.1) and those receiving sucrose (5.5), with a mean difference of 0.6 (95% confidence interval -1.6 to 2.8; P = .58). From this study, it cannot be concluded that breast milk has a better analgesic effect than sucrose in late preterm infants. From the results, it follows with 95% confidence that the analgesic effect of breast milk is not >1.6 points better and not > 2.8 points worse on the PIPP scale (SD 3.7) than the analgesic effect of sucrose in late preterm infants.
Richard, Sawadogo Wamtinga; Marius, Lompo; Noya, Somé; Innocent Pierre, Guissou; Germaine, Nacoulma-Ouedraogo Odile
This study investigated the general acute, anti-inflammatory, analgesic and antipyretic effects of methanol extract of Lepidagathis anobrya Nees (Acanthaceae). Carrageenan-induced rat paw edema and croton oil-induced ear edema in rats were used for the evaluation of general acute anti-inflammatory effects. Acetic acid-induced writhing response and yeast-induced hyperpyrexia in mice were used to evaluate the analgesic and antipyretic activities respectively. The extract at doses of 10, 25, 50 and 100 mgkg(-1) for carrageenan test and doses of 0.5 mg/ear for croton oil test induced a significant reduction (p < 0.001) of paw and ear edemas in rats. In the analgesic and antipyretic tests, the extract has shown a significant inhibition of writhes and hyperpyrexia with all the doses used when compared to the untreated control group. These results clearly show the anti-inflammatory, analgesic and antipyretic effects of the methanol extract of Lepidagathis anobrya and give the scientific basis for its traditional use. Further studies are needed to clarify the mechanism of action and the components responsible for these pharmacological effects.
Dickinson, Amy L; Leach, Matthew C; Flecknell, Paul A
Early maternal separation has profound effects on nociception in rats. Cross-fostering is a standard husbandry procedure used by some commercial breeders. This study aimed to determine if cross-fostering altered nociception and the analgesic efficacy of buprenorphine and morphine. At seven and nine weeks of age, an elevated plus maze was used to assess anxiety and Hargreaves apparatus was used to measure thermal nociception at two intensities in cross-fostered and naturally-reared rats. At 10 weeks of age these rats were assigned to one of three treatment groups: saline, buprenorphine or morphine. The Hargreaves apparatus was used to evaluate the effect of analgesics on nociception. Differences were observed in nociception between the cross-fostered and naturally-reared rats at both intensities. At the lower intensity no significant differences were seen between the cross-fostered and naturally-reared rats post-administration of an analgesic. At the higher intensity significant differences were apparent. Morphine was less effective in inducing analgesia to thermal stimuli in cross-fostered rats compared with naturally-reared rats, whereas the opposite was found with buprenorphine which had a more pronounced analgesic effect in the cross-fostered rats. No significant differences in performance on an elevated plus maze were demonstrated between the cross-fostered and naturally-reared rats.
Ghasemi, Elmira; Heidari-Oranjaghi, Nima; Azhdari-Zarmehri, Hassan; Sadegh, Mehdi
Objective(s): Reduction of pharmacological effectiveness or tolerance appears following repeated administration of many analgesic drugs. We investigated tolerance to anti-nociceptive effects of orexin-A, an endogenous potent analgesic peptide using the hot-plate test. Materials and Methods: Orexin-A was microinjected ICV (intracerebroventricular) with an interval of 12 hr for 7 continuous days and its anti-nociceptive responses were measured on days 1, 4 and 7 using the hot-plate test following the first day of administration. Orexin-A was used at a dose of 100 pmol to induce analgesic effects. Results: ICV administration of orexin-A produced an effective anti-nociception on the first day of experiment as measured by hot-plate 5, 15, and 30 min after the injection, in comparison with both baselines (hot-plate test one day before the beginning of orexin-A administration and control, saline-administrated group). However, repeated administration of orexin-A on the following days revealed a significant reduction in this analgesic effect during day 4 to day 7. However, to rule out any associative tolerance resulting from learning related to experimental procedures and/or environmental cues, a single injection of orexin-A was administrated to animals of control group (which were receiving saline during 7 days of experiments) and the analgesic effect was observed. Conclusion: These results, for the first time, indicated the appearance of tolerance to anti-nociceptive effects of orexin-A, following repeated administrations of this agent. PMID:26877847
Joshi, G P
Inadequately treated pain is a major cause of unanticipated hospital admissions after ambulatory surgery. The ability to provide adequate pain relief by simple methods that are readily available to the day-care patient in his or her home environment is one of the major challenges for providers of ambulatory surgery and anesthesia. The increasing number of extensive and painful surgical procedures (e.g., laparoscopic cholecystectomy, laminectomy, knee construction, hysterectomies) being undertaken on an ambulatory basis presents new challenges with respect to acute postoperative pain. Hence the availability of more sophisticated and effective treatment modalities, such as ambulatory PCA and continuous local and regional anesthetic blocks, with minimal side effects, are necessary to optimize the benefits of ambulatory surgery for both patient and health care provider. However, outcome studies are needed to evaluate the effect of these newer therapeutic approaches with respect to postoperative side effects and other important recovery parameters. Recent studies suggest that factors other than pain per se must be controlled to reduce postoperative morbidity and facilitate the recovery process. Not surprisingly, the anesthetic technique can influence analgesic requirement in the early postoperative period. Although oral analgesic agents will continue to play an important role, the adjunctive use of local anesthetic agents is likely to assume an even greater role in the future. Use of drug combinations (e.g., opiates and local anesthetics, opiates and NSAIDs) may provide improved analgesia with fewer side effects. Finally, safer and simpler analgesic delivery systems are needed to improve our ability to provide cost-effective pain relief after ambulatory surgery. In conclusion, as a result of our enhanced understanding of the mechanisms of acute pain and the physiological basis of nociception, the provision of "stress-free" anesthesia with minimal postoperative
Antonisamy, P; Ignacimuthu, S
Violacein was isolated from Chromobacterium violaceum, a soil Gram negative bacterium collected from the forest water body soil sample of Kolli Hills; Tamil Nadu, India. In the present study the immunomodulatory, analgesic and antipyretic activities of violacein were investigated in wistar rats and mice. Analgesic effect was evaluated by acetic acid- induced writhing, formalin induced paw licking and hotplate tests. Immunomodulatory effect was investigated by using ovalbumin- induced active paw anaphylaxis and sheep red blood cells (SRBC)-induced DTH tests. Antipyretic activity was evaluated by yeast- induced hyperpyrexia in rats. The anti- oedema effect was compared with indomethacin. Violacein inhibited 42.9% of ovalbumin- induced edema. Further we found that violacein (40mg/kg b.w.) reduced the edema induced by sheep red blood cells. Violacein also produced significant (p<0.05) analgesic activity in acetic acid induced writhing response, formalin induced paw licking response and hot plate analysis. Treatment with violacein showed a significant (p<0.05) dose-dependent reduction in pyrexia in rats. The results suggest that violacein possesses potent immunomodulatory, analgesic and antipyretic activities.
Moon, Jee Youn; Lee, Shin Young; Lee, Mi Kyung; Kim, Jung Eun; Lee, Ji Eun; Lee, So Hyun
Background Nefopam is a non-opioid, non-steroidal, centrally acting analgesic drug. The concomitant use of opioids and nefopam is believed to have many advantages over the administration of opioids alone for postoperative pain management. We conducted a randomized, double-blind study to determine the fentanyl-sparing effect of co-administration of nefopam with fentanyl for postoperative pain management via patient controlled analgesia (PCA). Methods Ninety female patients who underwent laparoscopic total hysterectomy under general anesthesia were randomized into 3 groups, Group A, fentanyl 1,000 µg; Group B, fentanyl 500 µg + nefopam 200 mg; and Group C, fentanyl 500 µg + nefopam 400 mg, in a total volume of 100 ml PCA to be administered over the first 48 h postoperatively without basal infusion. The primary outcome was total fentanyl consumption during 48 h; secondary outcomes included pain scores and incidence of side effects. Results Eighty-one patients were included in the analysis. The overall fentanyl-sparing effects of PCA with concomitant administration of nefopam during the first 48 h postoperatively were 54.5% in Group B and 48.9% group C. Fentanyl use was not significantly different between Groups B and C despite the difference in the nefopam dose. There were no differences among the three groups in terms of PCA-related side effects, although the overall sedation score of Group B was significantly lower than that of Group A. Conclusions The concomitant administration of nefopam with fentanyl for postoperative pain management may allow reduction of fentanyl dose, thereby reducing the risk of opioid-related adverse effects. PMID:27103966
Bazin, Véronique; Bollot, Julie; Asehnoune, Karim; Roquilly, Antoine; Guillaud, Christian; De Windt, Ariane; Nguyen, Jean-Michel; Lejus, Corinne
Low dose of ketamine reduces postoperative pain and opioid consumption in adult studies. However, there are only a few data with controversial results in the paediatric population. The aim of this randomized controlled trial was to evaluate the use of low doses of intravenous ketamine on postoperative pain in children after surgery on the lower part of the body. Thirty-seven children with ASA 1 or 2 from 6 to 60 months of age, undergoing scheduled surgery, were prospectively enrolled in a double blind sequential trial using a triangular test, with analysis every 10 patients treated. The children were randomly assigned to intravenously receive saline or 0.15 mg kg(-1) ketamine before surgery, followed by a continuous infusion of 1.4 microg kg(-1) min(-1) over 24 h. After sevoflurane induction and tracheal intubation, a caudal anaesthesia was performed in all children (1 ml kg(-1) of bupivacaine 0.25% with epinephrine). The postoperative analgesic technique was standardized with intravenous paracetamol 15 mg kg(-1) 6 h(-1), rectal morniflumate (20 mg kg(-1) 12 h(-1)) and intravenous nalbuphine infusion 1.2 mg kg(-1) 24 h(-1) for 24 h. The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores, additional bolus of nalbuphine (if CHEOPS >7) and side effects were recorded from eye opening every 2 h over 24 h. The primary endpoint was the CHEOPS area under the curve. There was no difference in terms of additional bolus of nalbuphine as well as CHEOPS score area under the curve between groups, that is, 76 +/- 10 in the ketamine group versus 74 +/- 7 in the control group. No psychomimetic side effects were noted. The study failed to show any evidence of benefit of ketamine to improve analgesia in children when given in addition to a multimodal analgesic therapy with paracetamol, a NSAID and an opiate.
Talakoub, Reihanak; Abbasi, Saeed; Maghami, Elham; Zavareh, Sayyed Morteza Heidari Tabaei
Background: Cholecystectomy is considered as the most important and relatively common postoperative pain control often begins in recovery room by using systemic narcotics that may have some side effects. The aim of this study is to evaluate the effect of premedication with oral tizanidine on pain relief after elective laparoscopic cholecystectomy. Materials and Methods: In this double-blinded clinical trial, 70 adults of American Society of Anesthesiologist physiologic state 1 and 2 scheduled for elective laparoscopic cholecystectomy under general anesthesia were studied and randomly divided in two study and control groups. Ninety minutes before the induction of anesthesia, patients received either 4 mg tizanidine (study group) orally in 50cc or the same volume of plain water as a placebo (control group). Then, the vital signs, pain intensity, duration of stay in recovery, and the analgesic consumption were measured and then compared in both groups during 24 h postoperatively. Results: There was no significant difference in patient characteristics, with respect to age, weight, gender, and duration of anesthesia and surgery between the groups (P > 0.05). The pain intensity, need for analgesic drugs (34.57 ± 8.88 mg vs. 101.86 ± 5.08 mg), and the duration of stay in recovery room (67.43 ± 1.59 min vs. 79.57 ± 5.48 min) were significantly lower in tizanidine group than that of the control group. Conclusion: Oral administration of 4 mg tizanidine before laparoscopic cholecystectomy reduces postoperative pain, opioid consumption, and consequence of the duration of stay in recovery room without any complication. PMID:26962521
Rougeot, C; Robert, F; Menz, L; Bisson, J-F; Messaoudi, M
Human opiorphin QRFSR-peptide protects enkephalins from degradation by human neutral endopeptidase (hNEP) and aminopeptidase-N (hAP-N) and inhibits pain perception in a behavioral model of mechanical acute pain (1). Here, using two other pain rat models, the tail-flick and the formalin tests, we assess the potency and duration of the antinociceptive action of opiorphin with reference to morphine. The occurrence of adverse effects with emphasis on the side-effect profile at equi-analgesic doses was compared. We demonstrate that opiorphin elicits minimal adverse morphine-associated effects, at doses (1-2 mg/kg, i.v.) that produce a comparable analgesic potency in both spinally controlled thermal-induced acute and peripheral chemical-induced tonic nociception. The analgesic response induced by opiorphin in the formalin-induced pain model preferentially requires activation of endogenous mu-opioid pathways. However, in contrast to exogenous mu-opioid agonists such as morphine, opiorphin, does not develop significant abuse liability or antinociceptive drug tolerance after subchronic treatment. In addition, anti-peristaltism was not observed. We conclude that opiorphin, by inhibiting the destruction of endogenous enkephalins, which are released according to the painful stimulus, activates restricted opioid pathways specifically involved in pain control, thus contributing to a greater balance between analgesia and side-effects than found with morphine. Therefore, opiorphin could give rise to new analgesics endowed with potencies similar to morphine but with fewer adverse effects than opioid agonists. Its chemical optimization, to generate functional derivatives endowed with better bioavailability properties than the native peptide, could lead to a potent class of physiological type analgesics.
de la Barrera-Núñez, María C.; Yáñez-Vico, Rosa M.; Batista-Cruzado, Antonio; Heurtebise-Saavedra, Jean M.; Castillo-de Oyagüe, Raquel
Objectives: To evaluate the anti-inflammatory and analgesic effect of Bromelain (pineapple extract) administered orally in the postoperative after extraction of impacted lower molars. Study Design: This is a prospective, placebo-controlled, unicentric, double-blind study; the sample size was 34 patients. The pre and postoperative outcomes, evaluated on the third (D3) and eighth day (D8), included inflamtion, pain and oral aperture, as well as the need for analgesics. One group received bromelain 150mg per day for three days and 100mg on days 4 to 7. The other group received placebo in the same dosage. All outcomes werrecorded quantitatively and analyzed with the Mann-Whitney U test for independent samples. Results: Although there were no statistically significant differences between the treatment groups, a trend towards less inflammation and improved oral aperture was observed in the group that received bromelain, compared to the group that received placebo. This trend can be attributed completely to random reasons, since there is no statistical difference in the results. Conclusions: Further studies are necessary to analyze different administration patterns and doses of bromelain for the use in the postoperative of impacted third molars. Key words:Tooth extraction, third molar, postoperative period, bromeline, clinical study. PMID:24316697
Polomano, Rosemary C; Fillman, Mechele; Giordano, Nicholas A; Vallerand, April Hazard; Nicely, Kelly L Wiltse; Jungquist, Carla R
: Multimodal analgesia, which combines analgesic drugs from different classes and employs analgesic techniques that target different mechanisms of pain, is recommended in the treatment of acute postoperative and trauma-related pain because its synergistic effect maximizes pain relief at lower analgesic doses, thereby reducing the risk of adverse drug effects. Using a case-based approach, this article reviews various multimodal analgesic therapies used in the treatment of acute pain; discusses their benefits; and summarizes findings from related research, recommendations from evidence-based practice guidelines, and expert consensus reports.
Bednarczyk-Cwynar, Barbara; Zaprutko, Lucjusz; Marciniak, Joanna; Lewandowski, Grzegorz; Szulc, Michal; Kaminska, Ewa; Wachowiak, Natalia; Mikolajczak, Przemyslaw Lukasz
The new derivative of well-known triterpene, oleanolic acid: methyl 3-octanoyloxyiminoolean-12-en-28-oate 5, was synthesized by the action of caprylic acid on methyl oleanolate 3-oxime in the presence of dicyclohexylcarbodiimide in dioxane. The molecular structure of the obtained product 5 was confirmed by spectral methods. The acute toxicity, locomotor activity, and the dose-dependent analgesic activity were studied. In addition, the effect of compound 5 on morphine-induced analgesic activity, the dose-dependent anti-inflammatory activity and the effect of the compound on diclofenac anti-inflammatory activity study were performed. The results proved a low toxicity (LD₅₀ > 2 g/kg) of the tested product 5, which affected neither vertical nor horizontal locomotor activity in the given range of doses. The triterpene 5 also produced centrally mediated (morphine-like) analgesic action; however, only in the highest dose. The synergistic analgesic activity of 5 and morphine in the doses of 30.0 and 300.0mg/kg was found. Compound 5 expressed the anti-inflammatory action which did not affect the anti-inflammatory activity of diclofenac after their combined administration.
Akdere, Hakan; Oztekin, Ilhan; Arda, Ersan; Aktoz, Tevfik; Turan, Fatma Nesrin; Burgazli, Kamil Mehmet
Background: Chronic Nonbacterial Prostatitis (CNBP) is a condition that frequently causes long-term pain and a significant decrease in the quality of life. Objectives: The present study aimed to examine the analgesic effects of oligonol, acupuncture, quantum light therapy and their combinations on estrogen-induced CNBP in rats. Materials and Methods: This experimental study was conducted in Edirne, Turkey, using a simple randomized allocation. A total of 90 adult male Wistar rats were randomized into 9 groups of 10 rats each: Group I, control; Group II, CNBP, Group III, oligonol only, Group IV, acupuncture only; Group V, quantum only; Group VI, oligonol + quantum; Group VII, acupuncture + oligonol; Group VIII, quantum + acupuncture; Group IX, acupuncture + quantum + oligonol. Oligonol treatment was given at a dose of 60 mg/day for 6 weeks. Conceptual vessels (CV) 3 and 4, and bilaterally urinary bladder (Bl) 32 and 34 points were targeted with 1-hour acupuncture stimulation. The quantum light therapy was applied in 5-minute sessions for 6 weeks (3-times/a week). For pain measurements, mechanical pressure was applied to a point 2 cm distal to the root of the tail to elicit pain and consequent parameters (peak force, latency time of response and total length of measurement) were assessed. Results: Analgesic effects were observed with all treatment regimens; however, the most prominent median analgesic effect was shown in the quantum light therapy in combination with acupuncture for estrogen-induced CNBP (PF1 = 663.9, PF2 = 403.4) (P = 0.012). Furthermore, we observed that monotherapy with quantum light showed a better analgesic efficacy as compared to oligonol and acupuncture monotherapies (PF1 = 1044.6, PF2 = 661.2) (P = 0.018, P = 0.008, P = 0.018; respectively). Conclusions: All treatment modalities showed a significant analgesic effect on CNBP in rats, being most prominent with the quantum light therapy. PMID:26023344
Onset of analgesia and analgesic efficacy of tramadol/acetaminophen and codeine/acetaminophen/ibuprofen in acute postoperative pain: a single-center, single-dose, randomized, active-controlled, parallel-group study in a dental surgery pain model.
Jung, Young-Soo; Kim, Dong Kee; Kim, Moon-Key; Kim, Hyung-Jun; Cha, In-Ho; Lee, Eui-Wung
pain intensity difference was significantly greater with Co/Ac/Ib at 5 to 6 hours. The proportion of patients assessing their assigned treatment as good or better was significantly greater with Co/Ac/Ib compared with Tr/Ac (P < 0.05). The safety profile of Tr/Ac was comparable to that of Co/Ac/Ib. In this small and selected group of subjects, the onset of analgesia and analgesic efficacy of Tr/Ac was comparable to that of Co/Ac/Ib. Tr/Ac provided rapid and effective analgesia for acute postoperative dental pain in this population.
Panagiotou, Irene; Mystakidou, Kyriaki
The exact effect of opioid analgesics on sleep is to be determined. Although literature data are sporadically reported, the aim of this review is to summarize the already known effects of such medications on sleep. A variety of effects, both positive and negative, has been suggested, when opioids are used for pain treatment, but in the absence of pain as well. Although often thought to promote restful sleep, the reality is much more complicated. Sleep disturbances and alterations of sleep quantity and quality have been reported. In addition, their sedative effects have been relatively well established and opioids can cause respiration to slow and become irregular, leading to hypercapnia and hypoxia. As a result, their usage has been linked to irregular or ataxic breathing (Biot's breathing) and their use has been associated with both central and obstructive sleep apnea. One could estimate that central apnea is a common complication of such chronic therapy, affecting between 30% and 90% of patients. Thus, sleep disturbances can be induced or deteriorated. On the other hand, extended release opioid formulations have been suggested to improve sleep due to no analgesic gaps and less walking because of breakthrough pain. Furthermore, several reports have shown significantly improved sleep quantity and adequacy, with reduced sleep disturbances. Still, as no prospective trials on the effect of opioid therapy on sleep are available and evidence is scarce, definitive conclusions cannot be drawn. Future studies with their effect on sleep as primary end-point are needed to draw permanent conclusions.
Jarineshin, Hashem; Fekrat, Fereydoon; Kashani, Saeed
Background and Aim: Meperidine and paracetamol are frequently used in postoperative pain control. We evaluated the effect of paracetamol versus meperidine on postoperative pain control of elective cesarean section in patients under general anesthesia. Materials and Methods: In this randomized double-blind study, seventy mothers’ candidate for cesarean section under general anesthesia were randomized in paracetamol group (n = 35), received 1 g paracetamol in 100 ml normal saline, and meperidine group (n = 35), received 25 mg meperidine in 100 ml normal saline and then compared regarding the pain and vomiting severity based on visual analog scale (VAS). Results: Two groups did not show significant difference regarding pain score based on VAS during 30 min after surgery in the recovery room, however, the pain score after 30 min in paracetamol group was significantly more than meperidine group. The difference between two groups regarding pain score in surgery ward at 0, 2, 4, 6 h, were not significant, however, pain score after 6 h in meperidine group was significantly lower than paracetamol group. The score of vomiting based on VAS in the recovery room in meperidine group was marginally more than paracetamol group (P > 0.05). The score of vomiting, based on VAS in meperidine group was significantly more than paracetamol group during the 24 h in the surgery ward. The analgesic consumption in meperidine group during 24 h after surgery was significantly lower than paracetamol group. Conclusion: We indicated that the meperidine decreased postoperative pain score and analgesic consumption more than paracetamol, but increased the vomiting score. PMID:28298778
Mokhtari, Fatemeh; Yazdi, Kamal; Mahabadi, Amir Mohammad; Modaresi, Seyed Jalil; Hamzeheil, Zeinab
Introduction: Post-endodontic pain is one of the main problems for both patients and dentists. The purpose of this study was to compare the effectiveness of premedication with indomethacin and ibuprofen for management of postoperative endodontic pain. Methods and Materials: In this clinical trial, mandibular molars with irreversible pulpitis were endodontically treated in 66 patients. The medicines were prepared similarly in the form of capsules containing 400 mg ibuprofen (group A), 25 mg indomethacin (group B) and placebo (group C). The patients were given one capsule 1 h before the start of treatment. Patients recorded their pain measured by a visual analogue scale (VAS) at medication time, during treatment and 8, 12 and 24 h after treatment. The data were analyzed using the chi-square, repeated measures ANOVA, paired t-test, Tamhane and Pearson correlation coefficient. Results: Ibuprofen and indomethacin significantly reduced the postoperative pain in comparison with placebo during treatment and 8 h after treatment; however, there were no significant differences between them 12 and 24 h after treatment. Conclusion: Premedication with ibuprofen and indomethacin can effectively control short term post-operative pain; the lower incidence of side effects and greater analgesic power of ibuprofen make it a superior choice. PMID:26843879
Qiu, Fen; Tian, Hui; Zhang, Zhi; Yuan, Xian-Ling; Tan, Yuan-Feng; Ning, Xiao-Qing
To study the effects of hemostasis, analgesic and anti inflammation of the alcohol extract of Hibiscus tiliaceus and offer pharmacological and experimental basis for its safe and effective use in clinic. The effects of hemostasist were observed with tail breaking method, capillary tube method and slide method; Hot board and body distortion induced by acetic acid methods were applied in mice analgesia experiment, the mice model of acute auricle swelling induced by dmi ethylbenzene and capillary permeability induced by acetic acid were applied to observe the anti inflammatory effects. The alcohol extract of Hibiscus tiliaceus could significantly reduce the bleeding time and the clotting time, delay the plant reaction time and reduce the writhing times of the mice, and it also had effect on inhibiting swelling of mice ear and the permeability of the capillary. These results suggest that the alcohol extract of Hibiscus tiliaceus has the effects of hemostasis, analgesic and anti inflammation.
Saki, K; Bahmani, M; Rafieianb-Kopaei, M D; Asadollahi, K; Emaneini, M; Taherikalani, M
The first step for identification of medicinal plants and their therapeutic effects is to determine their use by local people, traditional medicine books and personal experiences. The aim of this study was to document the medicinal plants used as analgesic, sedative or narcotic agents by local residents of Dehloran, Iran. Interviews conducted with 53 informants (38 male and 15 female) revealed that a total of 32 medicinal plants belonging to 22 families are used in Dehloran as narcotic, sedative and analgesic agents. The most utilized plant families were Asteraceae, Rosaceae and Fabaceae. Approximately 74% of the utilized plants was attributed to herbs, followed by trees (13%) and shrubs (13%). Sixty-six percent of the medicinal plants used in the study area were perennial and the rest were annual or biannual. The most widely used plant parts were flowers (34%) followed by leaves (24%) and fruits (14%). Thirty-nine percent of the medicinal plants were used as sedatives, 39% as analgesics, and 24% as narcotics. Recommended plants in this study can be good candidates for further clinical and laboratory trials on diseases that are associated with pain, suffering, stress and depression. They also can be used to develop new sedative, narcotic and analgesic drugs.
Hoek, Amber E; De Ridder, Maria A J; Bayliss, Antonia; Patka, Peter; Rood, Pleunie P M
Pain is a common presenting complaint of emergency department patients. Providing instructions that can be easily recalled by patients is an important step in enabling patients to manage their pain following discharge. The effect of the introduction of written discharge instructions for pain medication on patients' recall of instructions was evaluated in this study. A patient-control study within a prospective follow-up study was performed. In the first phase, no written discharge instructions were available. Patients discharged on analgesics filled in a digital questionnaire regarding correct analgesics use. In the second phase, patients were discharged with additional written instructions and completed the same questionnaire. In the first phase, 40% of patients correctly recalled instructions for taking analgesics. In the second phase, significantly more patients, 71% (P<0.01), were able to recall the instructions correctly. Results of this study support the hypothesis that it makes sense to provide patients with written instructions about the appropriate use of analgesics, and that emergency departments that are not yet doing this should consider introducing this policy. It is a relatively low-cost measure that could lead to a significant improvement in quality of care.
Jung, Kyeo-Woon; Kang, Hyeon-Wook; Park, Chan-Hye; Choi, Byung-Hyun; Bang, Ji-Yeon; Lee, Soo-Han; Lee, Eun-Kyung; Choi, Byung-Moon; Noh, Gyu-Jeong
Oxycodone is a μ-opioid receptor agonist and is generally indicated for the relief of moderate to severe pain. The aim of this study was to compare the analgesic efficacy of patient-controlled oxycodone and fentanyl for postoperative pain in patients undergoing colorectal surgery. Patients scheduled to undergo elective colorectal surgery (n=82) were allocated to receive oxycodone (n=41, concentration of 1 mg/mL) or fentanyl (n=41, concentration of 15 μg/mL) for postoperative pain management. After the operation, pain using a numerical rating scale (NRS), delivery to demand ratio, infused dose of patient-controlled analgesia (PCA), side effects, and sedation levels were evaluated. Median (25%-75%) cumulative PCA dose of oxycodone group at 48 hours (66.9, 58.4-83.7 mL) was significantly less than that of fentanyl group (80.0, 63.4-103.3 mL, P=.037). Six hours after surgery, the mean (SD) NRS scores of the oxycodone and fentanyl groups were 6.2 (2.4) and 6.8 (1.9), respectively (P=.216). The mean equianalgesic potency ratio of oxycodone to fentanyl was 55:1. The groups did not differ in postoperative nausea, vomiting, and level of sedation. Patient-controlled oxycodone provides similar effects for pain relief compared to patient-controlled fentanyl in spite of less cumulative PCA dose. Based on these results, oxycodone can be a useful alternative to fentanyl for PCA in patients after colorectal surgery. © 2016 John Wiley & Sons Australia, Ltd.
Liu, M; Liu, X; Liu, B
The modulation of red nucleus (RN) to pain sense was researched with the latent period of radiant-heat tail flick of rats as standard of the pain threshold. The pain threshold of tail flick reflex was raised significantly by bilateral injection of glutamic acid into RN. Simultaneous injecting glutamic acid into RN and lidocaine into nucleus raphe magnus (NRM) could attenuate the raising effect of pain threshold of RN. This showed that the activated RN has analgesic effect and the NRM plays an important role in the descending inhibitory pathway of RN. The discharges of neurons in caudal part of nucleus spinalis tract nervi trigemini (cNST) evoked by stimulating nerve alveolaris inferior (nAI) with strong pulse were recorded with microelectrode. The nAI-evoked discharges might be inhibited by stimulating contralateral or ipsilateral RN. The RN inhibitory time course on nAI-evoked discharges were shortened after injecting lidocaine into NRM. This demonstrated that the inhibitory effect of RN on neurons in cNST is mediated by NRM. The electrical stimulation of acupoint "Jiache" could inhibit the pain-evoked discharges of neurons in cNST. The inhibitory time course of electrical acupuncture were prolonged by stimulating RN. This result revealed that the activated RN can strengthen the analgesic effect of acupuncture.
Rocke, Daniel; Sharp, Scott; Wiener, Dana; Puscas, Liana; Lee, Walter T
1) Evaluate the effectiveness of a postoperative disposition protocol for upper airway surgery in patients with sleep apnea. 2) Compare the cost-effectiveness of outpatient and overnight observational sleep apnea surgery versus surgical intensive care admission determined by preoperative screening criteria. A new preoperative protocol for sleep apnea surgery was instituted at the Durham Veterans Affairs Medical Center in 2008 to triage patients undergoing sleep apnea surgery to one of three postoperative dispositions: intensive care, routine ward bed, or discharge home. An Institutional Review Board approved retrospective chart review of patients undergoing sleep apnea surgery between May 2008 and January 2012 was performed. Postoperative complications and cost comparisons were assessed between each of the three postoperative disposition groups. 115 patients underwent sleep apnea surgery between July 2008 and January 2012. 11 patients were excluded leaving 104 patients in the final analysis. Median follow-up was 1.25months. Overall complication rate was 12.5%. Eight complications occurred in the group triaged to intensive care, and 5 occurred in those triaged to lesser levels of postoperative care. All serious complications occurred during the immediate postoperative period. Based on only room charges, $125,275 was saved over the 3.6years of this study. A post operative disposition protocol can be effectively used to triage patients to less than intensive postoperative care. In institutions like the Durham VA, where sleep apnea patients were routinely triaged to intensive care, postoperative resources will be more efficiently utilized. Published by Elsevier Inc.
Raffa, Robert B.; Pergolizzi, Joseph V.; Tallarida, Ronald J.
When the pathophysiology of a medical condition is multi-modal, i.e., related to multiple physiological causes or mediated by multiple pathways, the optimal strategy can be to use a drug or a combination of drugs that contribute multiple mechanisms to the therapeutic endpoint. In such situations, a rational multi-modal approach can also result in the fewest adverse effects. We discuss the quantitative analysis of multi-modal action using the treatment of pain as a practical example and give examples of its application to some widely used analgesic drugs. PMID:20338825
Fitzpatrick, Courtney L; Weir, Heather L; Monnet, Eric
To determine the effects of infiltration of the incision site with bupivacaine hydrochloride as part of a multimodal analgesia protocol (incisional block) on postoperative analgesia and incisional healing. Randomized controlled clinical trial. 92 shelter-owned female dogs undergoing routine ovariohysterectomy. As part of a multimodal analgesic protocol for ovariohysterectomy, dogs received 1 of the following treatments at the incision site: no injection (26 dogs), preincisional infiltration with saline (0.9% NaCl) solution (12 dogs) or bupivacaine (21 dogs), or postincisional infiltration with bupivacaine (33 dogs). Postoperative pain was assessed with the Glasgow pain scale and response to mechanical stimulation with von Frey filaments. Incisions were monitored for signs of inflammation (edema, erythema, and discharge) and complications in wound healing. There was no difference in pain scores or response to mechanical stimulation over time among treatments. There were no significant differences in incisional edema or discharge among treatments. There was significantly more erythema in dogs that received preincisional infiltration with saline solution at 4 hours after surgery and less erythema in dogs that received postincisional infiltration with bupivacaine at 24 hours after surgery, compared with other treatments. The number of complications for dogs that had preincisional infiltration of bupivacaine was higher than for dogs that had other treatments; complications included excessive inflammation, splenic laceration, and herniation. No additional analgesic benefit was found in dogs that underwent local bupivacaine infiltration as part of a multimodal analgesic protocol for ovariohysterectomy.
Manchenko, D M; Glazova, N Iu; Levitskaia, N G; Andreeva, L A; Kamenskiĭ, A A; Miasoedov, N F
Heptapeptide Semax (MEHFPGP) is the fragment of ACTH(4-10) analogue with prolonged neurotropic activity. The aim of the present work was to study the Semax effects on learning capability and pain sensitivity in white rats following intraperitoneal and intranasal administration in different doses. Semax nootropic effects were studied in the test of acquisition of passive avoidance task. Pain sensitivity was estimated in Randall-Selitto paw-withdrawal test. It was shown that Semax exerts nootropic and analgesic activities following intraperitoneal administration. Analysis of dependence of these effects on dose resulted in different dose-response curves. Following intranasal administration, Semax was more potent in learning improvement compared to intraperitoneal administration. The peptide failed to affect the animal pain sensitivity following intranasal administration as opposed to intraperitoneal administration. The data obtained suggest different mechanisms and brain structures involved in realization of the nootropic and analgesic effects of Semax.
Blågestad, Tone; Nordhus, Inger H; Grønli, Janne; Engesæter, Lars B; Ruths, Sabine; Ranhoff, Anette H; Bjorvatn, Bjørn; Pallesen, Ståle
Total hip arthroplasty (THA) has been shown to reduce pain and improve function. In addition, it is suggested that THA improves sleep and alleviates symptoms of anxiety and depression. Patients with chronic pain are frequent users of analgesic and psychotropic drugs and thereby risk adverse drug events. The impact of THA on such drug use has not been thoroughly investigated. Based on merged data from the Norwegian Prescription Database and the Norwegian Arthroplasty Register, this study sought to investigate redeemed medications in a complete population (N = 39,688) undergoing THA in 2005 to 2011. User rates and redeemed drug volume of analgesics (nonsteroid anti-inflammatory drugs (NSAIDs), opioids, and nonopioids) and psychotropics (hypnotics, anxiolytics, and antidepressants) were calculated for 4 quarters before and 4 quarters after surgery. We analysed preoperative prescription trends (Q1 vs Q4), postoperative prescription (Q4 vs Q5), and long-term effect of surgery (Q4 vs Q8). Before surgery, use of all drug groups increased from Q1 to Q4. Use of opioids, nonopioids, and hypnotics dramatically increased from Q4 to Q5. Long-term (Q4 vs Q8) surgery reduced prescriptions of analgesics, hypnotics, and anxiolytics, but not antidepressants. Overall, the present results extend the positive effects of THA to include reduced reliance on medication to alleviate symptoms.
Saad, Sherin S T; Hamza, May; Bahr, Mohamed H; Masoud, Somaia I
Control of postoperative pain is far from satisfactory. Yet, non-steroidal anti-inflammatory drugs (NSAIDs) remain an important choice. The production of nitric oxide (NO), which plays an important role in the development and maintenance of inflammatory hyperalgesia, is inhibited by NSAIDs. Monoamines also play a key role in the modulation of nociception. The aim of the present work is to study the involvement of NO and monoamines in the antinociceptive mechanism of ibuprofen in postsurgical pain in mice. Surgical incision resulted in mechanical allodynia and increased spinal NO levels. The nitric oxide synthase inhibitor l-NAME (50mg/kg), administered intraperitoneally (i.p.), 30min before the incision decreased the development of postsurgical mechanical allodynia and reduced spinal NO levels. Ibuprofen (100 and 300mg/kg, i.p.), administered 30min before the incision, dose-dependently decreased both spinal NO levels and the development of mechanical allodynia. Administration of ibuprofen (100mg/kg i.p.), 20min following surgery, did not significantly reduce spinal NO level and resulted in a smaller antiallodynic effect. l-Arginine (600mg/kg i.p.), administered 20min before ibuprofen administration, restored both spinal NO level and mechanical allodynia in ibuprofen-treated mice. The selective alpha-2 adrenoceptor blocker yohimbine (4mg/kg i.p.), administered 30min before ibuprofen, also blocked ibuprofen effect on both mechanical allodynia and spinal NO level. These results suggest that inhibition of NO synthesis is involved in the analgesic activity of ibuprofen in post-surgical pain. Alpha-2 adrenoceptors are also involved in the analgesic activity of ibuprofen and NO may be involved in this mechanism.
A short survey about the different methods available for producing postoperative analgesia is given, the goal being to make it clear to the clinician that there are quite a number of techniques to be used although the everyday clinical practice often sticks to simple and not too effective methods of pain treatment following surgery. Initially presenting short informations about the neurophysiology of pain and the pathogenesis and causes of postoperative pain two main groups of producing analgesia are then discussed.Thefirst group deals with the systemic use of analgesics be it nonnarcotic analgesic antipyretics or narcotic analgesics (opioids). As for the first subgroup the peripheral action of these drugs (metamizol, acetylsalicylic acid, paracetamol) is brought about by blocking the synthesis of prostaglandins. These substances can only be used for very moderate postoperative pain f.i. following head and neck surgery. The strong acting opioids belong to the second subgroup. Recent informations on receptor sites in the brain and cord and the subgrouping of the receptors throws new light on the understanding of the different effects of these drugs and on the pathomechanisms of agonistic, antagonistic and mixed activities. The clinically used opioids then are mentioned (morphine, fentanyl, methadon, pethidin, piritramide, tilidin, buprenorphin and pentazocine) and dosage, duration of action, antagonisms and untoward side effects are presented. Stress is laid on the recent development of patient-controlled analgesia with all its advantages. Thesecond main group of methods for postoperative analgesia consists of regional anesthesia techniques as there are brachial plexus block, intercostal block and the continuous epidural analgesia using both local anesthetics and spinal opioids. The brachial plexus block in continuous form is absolutely able to prevent pain after operations in the shoulder-arm-region and can be prolonged even for weeks using catheter techniques. The
Minker, E; Végh, A; Blazsó, G
Methadone, azidomorphine, oxycodone and fentanyl inhibit synaptic transmission in isolated sympathetic ganglia of the frog and rat, just as did morphine and pethidine in our previous investigations. This inhibitory effect can be antagonized not only by naloxone and nalorphine but also by increasing calcium concentration of the perfusion fluid of the ganglia. The inhibitory effect on transmission of narcotic analgesics takes place on specific opiate receptors of the peripheral ganglia.
El Mansouri, Latifa; Bousta, Dalila; El Youbi-El Hamsas, Amal; Boukhira, Smahane; Akdime, Hassane
This study aims to investigate the antidepressant and analgesic properties of the aqueous extract of Anethum graveolens L. from South of Morocco (Rissani-Errachidia region). Extract of plant is obtained by aqueous decoction and administered to Wistar rats orally. The extract has a significant antidepressant and analgesic effects compared with the drug references (sertraline and tramadol) without any adverse effects. The dose of 250 mg/kg, body weight shows the best antidepressant and analgesic effects than 1 g/kg, body weight. Phytochemical study of the aqueous extract of the plant has to show its highlight in polyphenols, flavonoids, and tannins.
Litvak, K M; McEvoy, G K
Clinical studies of the injectable nonsteroidal anti-inflammatory agent (NSAIA) ketorolac tromethamine are reviewed, and the chemistry, pharmacology, pharmacokinetics, drug interactions, and adverse effects of ketorolac are described. Ketorolac exhibits anti-inflammatory, analgesic, and antipyretic activity. Although the exact mechanisms of action have not been determined, its effects appear to be associated principally with the inhibition of prostaglandin synthesis. After oral, i.m., or i.v. administration, ketorolac and its metabolites are excreted mainly in urine. Ketorolac tromethamine has been used for the symptomatic relief of moderate to severe postoperative pain, including that associated with abdominal, gynecologic, oral, orthopedic, or urologic surgery. Ketorolac has also been used for the relief of acute renal colic, pain associated with trauma, and visceral pain associated with cancer. When administered i.m., ketorolac produced analgesia comparable to that of i.m. doses of meperidine, pentazocine, or morphine. The most common adverse effects associated with short-term administration are nervous system and gastrointestinal effects; these are usually mild and occur in about 39% of patients. Unlike opiate analgesics, ketorolac does not appear to cause tolerance or physical dependence in patients receiving long-term therapy. Ketorolac tromethamine has been administered concomitantly with morphine or meperidine without apparent adverse interaction. For short-term pain management, an initial i.m. ketorolac tromethamine loading dose of 30 or 60 mg is recommended. Ketorolac tromethamine appears to be as effective as morphine or meperidine for short-term management of moderate to severe postoperative pain. It lacks the respiratory depressant effects of opiate analgesics but shares the toxic potentials of other NSAIAs.
Sayın, Pınar; Dobrucalı, Hale; Türk, Hacer Şebnem; Totoz, Tolga; Işıl, Canan Tülay; Hancı, Ayşe
The aim of this study was to compare the postoperative analgesic efficacy of intra-articularly injected levobupivacaine, levobupivacaine-fentanyl, and levobupivacaine-tramadol combinations. Eighty patients scheduled for elective knee arthroscopy were divided randomly into 4 groups of 20 patients each. Group 1 (the control group) received intra-articular saline, Group 2 received levobupivacaine 2.5 mg/ml, Group 3 received levobupivacaine 2.5 mg/ml + tramadol 50 mg, and Group 4 received levobupivacaine 2.5 mg/ml + fentanyl l50 mcg. All patients were operated on under general anesthesia, and a total of 20 ml study solution was injected: 7 ml subcutaneously before surgery and 13 ml intra-articularly upon completion of surgery. For postoperative, pain visual analogue scale (VAS) was assessed at the 1st, 2nd, 4th, 8th, 12th, and 24th hours postoperatively. Patients with a VAS score over 5 received diclofenac sodium, and the need for rescue analgesics was recorded. At the 1st, 2nd, 4th, 8th, 12th, and 24th postoperative hours, Group 3 and Group 4 had statistically significant lower VAS scores of pain (p<0.01). Postoperative rescue analgesic requirements were different among the groups. The postoperative 1st hour analgesic requirement was statistically significantly lower in Group 3 and Group 4 when compared to the other groups (p<0.01). At the postoperative 2nd and 4th hours, analgesic requirements were statistically significantly lower in Group 3 than in the other groups (p<0.01). Analgesic requirements were statistically significantly lower in Group 3 and Group 4 than in the other groups (p<0.01). Analgesic requirements at the 12th and 24th postoperative hours did not show any statistically significant difference (p>0.05). The results indicated that levobupivacaine combined with either fentanyl or tramadol decreased rescue analgesic requirements when compared to levobupivacaine alone.
Moller, Philip Lange; Juhl, Gitte Irene; Payen-Champenois, Catherine; Skoglund, Lasse Ansgar
We compared an acetaminophen (paracetamol) 1 g (n = 51) formulation for infusion with propacetamol 2 g (n = 51) and placebo (n = 50) in a randomized, controlled, double-blind, parallel group trial in patients with moderate-to-severe pain after third molar surgery. Treatment efficacy was assessed in house for 6 h after starting the 15-min infusion. Significant effects versus placebo (P < 0.01) were obtained with both active treatments on pain relief, pain intensity difference on a 100-mm visual analog scale, and on a categorical scale (except for propacetamol at 6 h). No significant differences were noted between active groups except at 1 h. Six-hour weighted sums of primary assessments showed significantly better efficacy than placebo (P < 0.0001) and no difference between active treatments. Median stopwatch time to onset of pain relief for active treatment was 6-8 min after infusion start. Active treatments showed comparable efficacy with a significantly longer duration of analgesia and better patients' global evaluation compared with placebo. The incidence of patients reporting local pain at the infusion site was significantly less frequent after IV acetaminophen or placebo (0%) in comparison with propacetamol (49%). In conclusion, acetaminophen 1 g and propacetamol 2 g were superior to placebo regarding analgesic efficacy, with a more frequent incidence of local pain at the infusion site for propacetamol.
Verginadis, Ioannis I; Simos, Yannis V; Velalopoulou, Anastasia P; Vadalouca, Athina N; Kalfakakou, Vicky P; Karkabounas, Spyridon Ch; Evangelou, Angelos M
Exposure to various types of electromagnetic fields (EMFs) affects pain specificity (nociception) and pain inhibition (analgesia). Previous study of ours has shown that exposure to the resonant spectra derived from biologically active substances' NMR may induce to live targets the same effects as the substances themselves. The purpose of this study is to investigate the potential analgesic effect of the resonant EMFs derived from the NMR spectrum of morphine. Twenty five Wistar rats were divided into five groups: control group; intraperitoneal administration of morphine 10 mg/kg body wt; exposure of rats to resonant EMFs of morphine; exposure of rats to randomly selected non resonant EMFs; and intraperitoneal administration of naloxone and simultaneous exposure of rats to the resonant EMFs of morphine. Tail Flick and Hot Plate tests were performed for estimation of the latency time. Results showed that rats exposed to NMR spectrum of morphine induced a significant increase in latency time at time points (p < 0.05), while exposure to the non resonant random EMFs exerted no effects. Additionally, naloxone administration inhibited the analgesic effects of the NMR spectrum of morphine. Our results indicate that exposure of rats to the resonant EMFs derived from the NMR spectrum of morphine may exert on animals similar analgesic effects to morphine itself.
Ribeiro, Marta M B; Santos, Sónia Sá; Sousa, David S C; Oliveira, Margarida; Santos, Sara M; Heras, Montserrat; Bardaji, Eduard; Tavares, Isaura; Castanho, Miguel A R B
The adverse side-effects associated with opioid administration restrain their use as analgesic drugs and call for new solutions to treat pain. Two kyotorphin derivatives, kyotorphin-amide (KTP-NH₂) and ibuprofen-KTP-NH₂ (IbKTP-NH₂) are promising alternatives to opioids: they trigger analgesia via an indirect opioid mechanism and are highly effective in several pain models following systemic delivery. In vivo side-effects of KTP-NH₂ and IbKTP-NH₂ are, however, unknown and were evaluated in the present study using male adult Wistar rats. For comparison purposes, morphine and tramadol, two clinically relevant opioids, were also studied. Results showed that KTP-derivatives do not cause constipation after systemic administration, in contrast to morphine. Also, no alterations were observed in blood pressure or in food and water intake, which were only affected by tramadol. A reduction in micturition was detected after KTP-NH₂ or tramadol administrations. A moderate locomotion decline was detected after IbKTP-NH₂-treatment. The side-effect profile of KTP-NH₂ and IbKTP-NH₂ support the existence of opioid-based mechanisms in their analgesic actions. The conjugation of a strong analgesic activity with the absence of the major side-effects associated to opioids highlights the potential of both KTP-NH₂ and IbKTP-NH₂ as advantageous alternatives over current opioids.
Nonaka, Takahiro; Hara, Marie; Miyamoto, Chisato; Sugita, Michiko; Yamamoto, Tatsuo
Acetaminophen is known to be a relatively weak analgesic with fewer side effects than nonsteroidal anti-inflammatory drugs (NSAIDs). This study aimed to determine whether intravenous (iv) acetaminophen produces comparable analgesic effects to those of flurbiprofen (positive control drug), an intravenously injectable NSAID, after partial mastectomies. The primary outcome assessed was pain intensity during the first 24 h after the operation, and the secondary outcome was the satisfaction rating at discharge. After obtaining Institutional Ethics Committee approval, a series of 40 consecutive female patients who were scheduled for partial mastectomies were enrolled. Participants were randomly divided into two groups: an acetaminophen (1000 mg × 3) group (group A) and a flurbiprofen (50 mg × 3) group (group F). Each drug was administered 15 min before the end of surgery, and at 6 and 12 h after the operation. Postoperative pain was evaluated using a 100-mm visual analog scale (VAS) at 3, 6, and 24 h postoperatively. Satisfaction rating was evaluated on a 5-point scale (very good, good, well, bad, and very bad). VAS scores (mm) with movement in groups A and F at 3, 6, and 24 h after the surgery were 22 vs. 28, 14 vs. 24, and 12 vs. 20.5 (median), respectively, with no significant differences between the two groups. Eighteen of 20 patients in group A and 20 of 20 patients in group F expressed a satisfaction rating of greater than good. Acetaminophen produces an equivalent analgesic effect to flurbiprofen in post-partial mastectomy patients.
Serdiuk, S E; Gmiro, V E
Intramuscular (i. m.) administration in the minimum effective dose (MED) of central analgesics of fentanyl and dipyrone, polyamine agonist spermine and also IEM-1460 (IEM-1460 is AMPA receptors antagonist and agonist of the NMDA polyamine receptor site) causes the maximal analgesic effect in the tail flick test in rats. The combined i.m. administration of dipyrone with IEM-1460 and spermine in threshold, noneffective alone doses according 1/5 part from their MED leads to decrease of MED dipyrone in the combination with IEM-1460 in 120 times, and MED dipyrone in combination with spermine--in 10 times. The combined i.m. administration of fentanyl with IEM-1460 and spermine in above mentioned threshold doses leads to decrease of MED fentanyl in the combination with IEM-1460 in 150 times, and MED fentanyl in the combination with spermine--in 15 times.
Hegana, Rahul; Toshikhane, Hemant Devaraj; Toshikhane, Sangeeta; Amin, Hetal
Introduction: Post-operative pain is Nociceptive i.e., anticipated unavoidable physiological pain which is caused due to tissue trauma. Drugs such as NSAIDs (Non Steroidal Anti Inflammatory Drugs) and Opioids are used for post-operative pain management but are associated with their own drawbacks. Karamardādi Yoga has been in use in Ayurvedic practice for analgesia. It is known to relieve pain and can be used to supplement anaesthesia and also get rid of adverse effect of modern analgesic drugs. Aims and Objective: To study the comparative effect of Karamardādi Yoga and Diclofenac sodium in post-operative pain management. Materials and Methods: Randomized clinical trial with Group A (Control Group: Tab Diclofenac sodium 50 mg as a single dose) and Group B (Trial Group: Cap Karamardādi Yoga 500 mg as a single dose). Those who had undergone haemorrhoidectomy operation under local anaesthesia were selected as per inclusion criteria. Vitals, desirable effect and undesirable effect, total surgical time, requirement of 1st dose of analgesic, requirement of rescue analgesic and pain determined by VAS (Visual Analog Scale) were the assessment criteria and were observed and recorded. Results: Karamardādi Yoga does not show any undesirable or serious ill effects and altered values of vitals as per statistical analysis. As per VAS scale, pain felt by Trial group was earlier than control group. Conclusions: Karamardādi Yoga has analgesic property but its analgesic property and pain threshold capacity is lesser than those of Diclofenac sodium. PMID:27621519
Hema, Vadakkoot Raghavan; Ramadas, Konnanath Thekkethil; Biji, Kannammadathy Poulose; Indu, Suseela; Arun, Aravind
Background: Effective management of postoperative pain is a part of well-organized perioperative care, which helps in reduced morbidity and improved patient satisfaction. Preventive analgesia can reduce acute and chronic pain by blocking the noxious inputs to pain pathways, preventing sensitization. Studies have reported efficacy of gabapentin as a preventive analgesic in perioperative pain. In this study, we aimed to determine whether preoperative gabapentin reduced postoperative pain and tramadol consumption after thyroidectomy under general anesthesia. Materials and Methods: Sixty patients scheduled for thyroidectomy were allocated to two groups of thirty each for this prospective, observational study. Patients in Group A and Group B received oral gabapentin 600 mg (6 × 10−4 kg) and diazepam 10 mg (1 × 10−5 kg), respectively, 2 h prior to surgery. Tramadol was given as rescue analgesic for postoperative pain with a verbal rating score of two. The analgesic efficacy of preoperative gabapentin was assessed in terms of postoperative pain scores at rest or swallowing, time to first rescue analgesic, and total tramadol consumption for 24 h. Ramsay sedation score and side effects of drug were also looked into. Results: Postoperative pain scores and total tramadol consumption were significantly lower in Group A during 24 h (P = 0.00). Time to first rescue analgesic was significantly prolonged in Group A (P = 0.001). Side effects were comparable. Conclusion: Oral gabapentin is effective as a preventive analgesic in reducing postoperative pain and tramadol consumption after thyroidectomy under general anesthesia. PMID:28928577
Ayatollahi, Vida; Faghihi, Safa; Behdad, Shokoufeh; Heiranizadeh, Najmeh; Baghianimoghadam, Behnam
Selection of anesthetic drugs for cesarean section requires many considerations. Anesthetic drugs for this purpose must prevent hemodynamic stress due to tracheal intubation, while inducing neonatal complications. This study was conducted to determine the effects of paracetamol given before induction of anesthesia on cardiovascular responses to tracheal intubation and postoperative pain in the mother, and on neonatal Apgar score. This double-blind randomized placebo-controlled trial included 60 women in ASA I, without underlying diseases and fetal distress, who were candidates for elective cesarean section under general anesthesia. Patients were divided into two groups of 30 patients. Patients in the paracetamol group received 1 g intravenous (IV) paracetamol 20 min before the operation, while those in the placebo group received 1 cc normal saline at the same time. In both groups, anesthesia was induced by sodium thiopental and succinylcholine. Maternal systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) were measured before and immediately upon induction of anesthesia, and at first and fifth minute after tracheal intubation. Neonatal effects were assessed by Apgar score. Postoperative pain was assessed by use of the visual analog scale (VAS). The dose of analgesic used and the time of the first analgesic request by patients postoperatively were recorded. The SBP, DBP, MAP and HR were controlled significantly better in paracetamol group than in placebo group (P < 0.05). The mean 1-min and 5-min Apgar scores of neonates did not differ between the groups. The VAS pain score was significantly lower in paracetamol group than in placebo group at all measuring times (P < 0.05). Also, paracetamol caused later first analgesic request and lower dose of analgesic needed to control pain postoperatively (P < 0.05). In conclusion, the results of our study suggested IV paracetamol to be an efficacious agent to decrease
Abu Ahmed, A.M.; Sharmen, Farjana; Mannan, Adnan; Rahman, Md Atiar
This research evaluated the phytochemical contents as well as the analgesic, cytotoxic, and antimicrobial effects of the methanolic extract of Alpinia nigra leaf. Phytochemical analysis was carried out using established methods. The analgesic effects of the extract were measured with the formalin test and tail immersion test. The antibacterial activity of the extract was evaluated using the disc diffusion technique. Cytotoxicity was assessed with the brine shrimp lethality bioassay. Data were analyzed with one-way analysis of variance using statistical software (SPSS, Version 19.0). The qualitative phytochemical screening of A. nigra leaf extract showed the presence of medicinally active secondary metabolites such as alkaloids, glycosides, cardiac glycosides, flavonoids, steroids, tannins, anthraquinone glycosides, and saponins. The extract at a dose of 200 mg/kg revealed a prevailed central nociception increasing the reaction time in response to thermal stimulation. The extract also showed a response to chemical nociceptors, causing pain inhibition in the late phase. The leaf extract (2 mg/disc) showed mild antibacterial activity compared to tetracycline (50 μg/disc). In the brine shrimp lethality bioassay, the LC50 (lethal concentration 50) value of the extract was found to be 57.12 μg/mL, implying a promising cytotoxic effect. The results evidenced the moderate analgesic and antibacterial effects with pronounced cytotoxic capability. PMID:26587396
Panthong, Ampai; Supraditaporn, Wanicha; Kanjanapothi, Duangta; Taesotikul, Tawat; Reutrakul, Vichai
Cissus quadrangularis, a medicinal plant indigenous to Asia and Africa, is used for many ailments, especially for the treatment of hemorrhoid. The effects associated with hemorrhoid, i.e. analgesic and anti-inflammatory activities as well as the venotonic effect of the methanol extract of C. quadrangularis (CQ) were assessed in comparison with reference drugs. In the analgesic test, CQ provoked a significant reduction of the number of writhes in acetic acid-induced writhing response in mice. CQ also significantly reduced the licking time in both phases of the formalin test. The results suggest peripheral and central analgesic activity of CQ. In acute phase of inflammation CQ elicited the inhibitory effect on the edema formation of the rats' ear induced by ethyl phenylpropiolate as well as on the formation of the paw edema in rats induced by both carrageenin and arachidonic acid. It is likely that CQ is a dual inhibitor of arachidonic acid metabolism. In addition, CQ exerted venotonic effect on isolated human umbilical vein similarly to the mixture of bioflavonoids, i.e. 90% diosmin and 10% hesperidin. The results obtained confirmed the traditional use of C. quadrangularis for the treatment of pain and inflammation associated with hemorrhoid as well as reducing the size of hemorrhoids.
Abu Ahmed, A M; Sharmen, Farjana; Mannan, Adnan; Rahman, Md Atiar
This research evaluated the phytochemical contents as well as the analgesic, cytotoxic, and antimicrobial effects of the methanolic extract of Alpinia nigra leaf. Phytochemical analysis was carried out using established methods. The analgesic effects of the extract were measured with the formalin test and tail immersion test. The antibacterial activity of the extract was evaluated using the disc diffusion technique. Cytotoxicity was assessed with the brine shrimp lethality bioassay. Data were analyzed with one-way analysis of variance using statistical software (SPSS, Version 19.0). The qualitative phytochemical screening of A. nigra leaf extract showed the presence of medicinally active secondary metabolites such as alkaloids, glycosides, cardiac glycosides, flavonoids, steroids, tannins, anthraquinone glycosides, and saponins. The extract at a dose of 200 mg/kg revealed a prevailed central nociception increasing the reaction time in response to thermal stimulation. The extract also showed a response to chemical nociceptors, causing pain inhibition in the late phase. The leaf extract (2 mg/disc) showed mild antibacterial activity compared to tetracycline (50 μg/disc). In the brine shrimp lethality bioassay, the LC50 (lethal concentration 50) value of the extract was found to be 57.12 μg/mL, implying a promising cytotoxic effect. The results evidenced the moderate analgesic and antibacterial effects with pronounced cytotoxic capability.
Benedetti, Fabrizio; Arduino, Claudia; Costa, Sara; Vighetti, Sergio; Tarenzi, Luisella; Rainero, Innocenzo; Asteggiano, Giovanni
Expectation/placebo-related mechanisms and specific effects of therapies show additive effects, such that a therapy is less effective if the placebo component is absent. So far, the placebo component has been disrupted experimentally by using covert administrations of treatments. Here, we show for the first time that disruption of expectation/placebo-related analgesic mechanisms may occur in a clinical condition, Alzheimer's disease (AD). In order to assess the placebo component of a therapy, we used the recently developed open-hidden paradigm. A local anesthetic was applied, either overtly or covertly, to the skin of AD patients to reduce burning pain after venipuncture. The placebo (psychological) component is represented by the difference between the analgesic effect after open (expected) and after hidden (unexpected) application. We correlated the placebo component with both cognitive status and functional connectivity among different brain regions. We found that AD patients with reduced Frontal Assessment Battery scores showed reduced placebo component of the analgesic treatment. We also found that the disruption of the placebo component occurred when reduced connectivity of the prefrontal lobes with the rest of the brain was present. Remarkably, the loss of these placebo-related mechanisms reduced treatment efficacy, such that a dose increase was necessary to produce adequate analgesia. These findings highlight the active role of cognition and prefrontal lobes in the therapeutic outcome and underscore the need of considering a possible revision of the therapeutic approach in Alzheimer patients in order to compensate for the loss of the endogenous expectation and placebo mechanisms.
Kang, Wen-bo; Yang, Qi; Guo, Yan-yan; Wang, Lu; Wang, Dong-sheng; Cheng, Qiang; Li, Xiao-ming; Tang, Jun; Zhao, Jian-ning; Liu, Gang; Zhuo, Min
Background Cancer pain, especially the one caused by metastasis in bones, is a severe type of pain. Pain becomes chronic unless its causes and consequences are resolved. With improvements in cancer detection and survival among patients, pain has been considered as a great challenge because traditional therapies are partially effective in terms of providing relief. Cancer pain mechanisms are more poorly understood than neuropathic and inflammatory pain states. Chronic inflammatory pain and neuropathic pain are influenced by NB001, an adenylyl cyclase 1 (AC1)-specific inhibitor with analgesic effects. In this study, the analgesic effects of NB001 on cancer pain were evaluated. Results Pain was induced by injecting osteolytic murine sarcoma cell NCTC 2472 into the intramedullary cavity of the femur of mice. The mice injected with sarcoma cells for four weeks exhibited significant spontaneous pain behavior and mechanical allodynia. The continuous systemic application of NB001 (30 mg/kg, intraperitoneally, twice daily for three days) markedly decreased the number of spontaneous lifting but increased the mechanical paw withdrawal threshold. NB001 decreased the concentrations of cAMP and the levels of GluN2A, GluN2B, p-GluA1 (831), and p-GluA1 (845) in the anterior cingulate cortex, and inhibited the frequency of presynaptic neurotransmitter release in the anterior cingulate cortex of the mouse models. Conclusions NB001 may serve as a novel analgesic to treat bone cancer pain. Its analgesic effect is at least partially due to the inhibition of AC1 in anterior cingulate cortex. PMID:27612915
Babalonis, Shanna; Lofwall, Michelle R.; Nuzzo, Paul A.; Walsh, Sharon L.
Oxymorphone is a semisynthetic μ-opioid agonist, marketed as a prescription analgesic purported to be twice as potent as oxycodone for pain relief. Oral formulations of oxymorphone were re-introduced in the United States in 2006 and reports of abuse ensued; however, there are limited data available on its pharmacodynamic effects. The current study aimed to examine the direct physiological effects, relative abuse liability, analgesic profile, and overall pharmacodynamic potency of oxymorphone in comparison to identical doses of oxycodone. Healthy, non-dependent opioid abusers (n=9) were enrolled in this within-subject, double-blind, placebo-controlled, 3-week inpatient study. Seven experimental sessions (6.5 hr) were conducted, during which an oral dose of immediate-release formulations of oxymorphone (10, 20, 40 mg), oxycodone (10, 20, 40 mg) or placebo was administered. An array of physiological, abuse liability and experimental pain measures was collected. At identical doses, oxymorphone produced approximately two-fold less potent effects on miosis, compared to oxycodone. Oxymorphone also produced lesser magnitude effects on measures of respiratory depression, two experimental pain models, and observer-rated agonist effects. However, 40 mg of oxymorphone was similar to 40 mg of oxycodone on several abuse-related subjective ratings. Formal relative potency analyses were largely invalid due to the substantially greater effects of oxycodone. Overall, oxymorphone is less potent on most pharmacodynamic measures, although at higher doses, its abuse liability is similar to oxycodone. These data suggest that the published clinical equianalgesic estimates may not be consistent with the observed direct physiological effects of opioids, results of experimental pain models or abuse liability measures, as assessed in the human laboratory. PMID:25130052
Panchgar, Vinayak; Shetti, Akshaya N.; Sunitha, H. B.; Dhulkhed, Vithal K.; Nadkarni, A. V.
Background: There is an upward surge in the use of laparoscopic surgeries due to various advantages when compared to open surgeries. Major advantages are, due to small incisions which are cosmetically acceptable and most of them are now daycare procedures. Problem of economic burden and hospital bed occupancy has been overcome with laparoscopic surgeries. All these advantages are not free from disadvantages, as hemodynamic changes such as hypertension; tachycardia and other surgical-related complications are commonly observed intraoperatively. Dexmedetomidine is one of the α2 agonist drugs which acts at both supraspinal and spinal level and modulate the transmission of nociceptive signals in the central nervous system. The basic effect of dexmedetomidine on the cardiovascular system is to decrease the heart rate and systemic vascular resistance with additional feature of opioid sparing effect. This drug has become an ideal adjuvant during general anesthesia, especially when stress is expected. Hence, the drug was studied in laparoscopic surgeries. Aims and Objectives: (a) To study the effect of dexmedetomidine on hemodynamic parameters during perioperative period in patients undergoing laparoscopic surgery. (b) To study the postoperative sedation score and analgesic requirement. (c) To study the side effect profile of dexmedetomidine. Settings and Design: Randomized double blind controlled trial. Subjects and Methods: After obtaining the Institutional Ethical Clearance, the study was conducted. Forty patients of American Society of Anesthesiologists Class I and II were enrolled in this randomized study. The patients were randomly divided into two groups; group normal saline (NS) and group dexmedetomidine. Patient received either NS or dexmedetomidine in group NS and group dexmedetomidine, respectively, depending upon the allocation. The infusion rate was adjusted according to; loading dose (1 μg/kg) over 10 min and maintenance dose (0.5 μg/kg/h) and
Hayes, K E; Raucci, J A; Gades, N M; Toth, L A
This study was designed to evaluate the efficacy of several analgesic regimens for use after intraperitoneal implantation of telemetry transmitters in mice. The lengths of time required for postoperative recovery of food and water intake, locomotor activity, and core temperature of mice that did not receive postsurgical analgesic medication were compared to those of mice that were given either an analgesic in the drinking water or buprenorphine injections. Many measured variables were not substantially altered by analgesic medications. However, ibuprofen-treated mice demonstrated significantly greater locomotor activity on days 2 through 5 after surgery and a more rapid return to stable postsurgical levels of activity and water intake as compared to those in untreated mice. These changes are consistent with potential analgesic efficacy of the ibuprofen treatment regimen. Buprenorphine injections elicited hyperactivity, hyperthermia, and reduced food and water intake during both the immediate postsurgical recovery period and after apparent recuperation from surgery, as compared to effects observed in saline-treated mice. Evaluating the effect of analgesic regimens on postsurgical changes in physiologic and behavioral variables can be useful in assessing the efficacy of analgesic treatments, but some changes may indicate pharmacologic effects that do not reflect pain relief.
Marvi, -; Iqbal, Javeid; Muhammad, Shafi; Ahmad, Mansoor
Present study was conducted on crude methanolic extract of stem and root of Taverniera glabra. In Pakistan T. glabra is found in the region of Balochistan only. T. glabra has numerous therapeutic uses in traditional medicine and it is also used for the pain relief. Current study was carried out to evaluate acute toxicity, analgesic and CNS depressant activity of the plant. Acute toxicity was carried out by oral administration of the T. glabra extract from 250 to 2000mg/kg oral dose. Analgesic activity was carried out by acetic acid induced writhing test and formalin test. Central Nervous System (CNS) depressant activity was carried out by exploratory activities (open field activity, cage crossing activity, rearing test) and forced swimming test. Oral administration of the methanolic extract of T. glabra was nontoxic at the dose of 1500mg/kg in the acute toxicity test. Exploratory behavior of mice treated with the methanolic extract of T. glabra showed sedative effects (P<0.05) in open field, cage crossing, traction and rearing test, particularly at the dose of 500mg as compared with standard drug Diazepam. In forced swimming test, mobility time was significantly (P<0.05) increased at 500mg/kg oral dose, and results were significant as compared with control. Methanolic extract of T. glabra produced significant (P<0.05) analgesic effects at the dose of 500mg/kg in the acetic acid induced writhing test and the formalin test. In conclusion, results show that the crude methanolic extract of T. glabra possess sedative as well as potent analgesic effects. Present pharmacological studies are the first ever studies conducted on the methanolic extract of T. glabra.
Segelman, Jerker; Pettersson, Hans Järnbert; Svensén, Christer; Divander, Mona-Britt; Barenius, Björn; Segelman, Josefin
Glucocorticoids are reported to improve postoperative analgesia. The purpose of the study was to investigate whether a preoperative, single dose of betamethasone could reduce pain after ambulatory arthroscopic knee surgery. This was a randomized, double-blind, placebo-controlled trial including patients scheduled for knee arthroscopy. The intervention was an intravenous injection of betamethasone 8 mg or placebo. The primary outcome was pain day 1 evaluated by a verbal descriptor scale (VDS). In total, 74 patients (betamethasone = 34; placebo = 40) were randomized. One patient in each group was excluded from analysis. During activity day 1 following surgery, the proportion with no or minor pain was significantly (p = 0.030) higher in the betamethasone group (22 of 33; 67 %) compared with the placebo group (17 of 39; 44 %). At rest, the corresponding figures were 26 of 33 (79 %) for betamethasone and 24 of 39 (62 %) for placebo (p = 0.062). After 3 months of follow-up, no patient receiving betamethasone experienced adverse events while six receiving placebo did (postoperative nausea and vomiting in five and delayed wound healing in one). An analgesic benefit was seen day 1 following surgery. This indicates that betamethasone has a place in ambulatory arthroscopic knee surgery. https://www.clinicaltrialsregister.eu/ (identifier 2009-014717-27).
Preparations from devil's claw differ in their content of active ingredients as assessed by the quantity of harpagoside present. The harpagoside content in the daily dose of Doloteffin (extraction solvent water) is double that of preparations extracted with 60% ethanol. Only preparations with proven effectiveness for painful lower back or arthrotic pain are an attractive alternative to synthetic analgesics, and are of substantial benefit in the treatment of chronic pain. From an evidence based view, extract with at least 50 mg harpagoside in the daily dose should be recommended for the treatment of pain. Treatment with devil's claw extract is associated with a lower risk of adverse events than treatment with synthetic analgesics, and may contribute in the majority of patients to the relief of pain.
Analgesics are agents which selectively relieve pain by acting in the CNS and peripheral pain mediators without changing consciousness. Analgesics may be narcotic or non-narcotic. The study of pain in animals raises ethical, philosophical, and technical problems. Both peripheral and central pain models are included to make the test more evident for the analgesic property of the plant. This chapter highlights methods such as hot plate and formalin and acetic acid-induced pain models to check the analgesic activity of medicinal plants.
Dorkham, Mariana C; Chalkiadis, George A; von Ungern Sternberg, Britta S; Davidson, Andrew J
Pain following ambulatory surgery is often poorly managed at home. Certain procedures, such as tonsillectomy, cause high levels of pain for at least 1 week postoperatively. This impacts significantly on recovery and postoperative morbidity with regards to oral intake, sleep, and behavior. Barriers to effective postoperative pain management at home following discharge have been investigated and incorporate: parental factors, such as the ability to recognize and assess their child's pain, and misconceptions about analgesics; child factors, such as refusal to take medication; medication factors, such as ineffective medication or inadequate formulation or dose of analgesics; and system factors, such as poor discharge instructions, difficulty in obtaining medication and lack of information provision. A number of interventions have been suggested and trialled in an effort to address these barriers, which encompass educational strategies, improved information provision, improved medication regimens, and the provision of tools to aid parents in the pain management of their children. All in all, improvements in pain outcomes have been minor, and a more holistic approach, that appreciates the complex and multifaceted nature of pain management at home, is required.
de la Barrera-Núñez, M-C; Yáñez-Vico, R-M; Batista-Cruzado, A; Heurtebise-Saavedra, J-M; Castillo-de Oyagüe, R; Torres-Lagares, D
To evaluate the anti-inflammatory and analgesic effect of Bromelain (pineapple extract) administered orally in the postoperative after extraction of impacted lower molars. This is a prospective, placebo-controlled, unicentric, double-blind study; the sample size was 34 patients. The pre and postoperative outcomes, evaluated on the third (D3) and eighth day (D8), included inflamtion, pain and oral aperture, as well as the need for analgesics. One group received Bromelain 150mg per day for three days and 100mg on days 4 to 7. The other group received placebo in the same dosage. All outcomes werrecorded quantitatively and analyzed with the Mann-Whitney U test for independent samples. Although there were no statistically significant differences between the treatment groups, a trend towards less inflammation and improved oral aperture was observed in the group that received Bromelain, compared to the group that received placebo. This trend can be attributed completely to random reasons, since there is no statistical difference in the results. Further studies are necessary to analyze different administration patterns and doses of Bromelain for the use in the postoperative of impacted third molars.
Kellstein, D; Ott, D; Jayawardene, S; Fricke, J
This randomised, double-blind, placebo-controlled, parallel-group study compared the efficacy and tolerability of lumiracoxib (a novel COX-2 selective inhibitor) with rofecoxib, celecoxib and placebo in patients with moderate-to-severe post-operative dental pain. Following third molar extraction, patients received single oral doses of lumiracoxib 400 mg, rofecoxib 50 mg, celecoxib 200 mg or placebo (n = 355). Additional patients from a similar study, assigned to lumiracoxib, rofecoxib or placebo (n = 155), were included for analysis of the primary variable, Summed Pain Intensity Difference over the first 8 h post dose (SPID-8). For SPID-8, lumiracoxib was superior to rofecoxib (p < 0.05), celecoxib (p < 0.001) and placebo (p < 0.001). Lumiracoxib demonstrated the fastest onset of analgesia and the longest time to rescue medication use. Patient global evaluation of lumiracoxib was comparable to rofecoxib and superior to celecoxib and placebo. All treatments were well tolerated. Lumiracoxib 400 mg provides rapid, effective and sustained relief of post-operative dental pain, comparable or superior to rofecoxib.
Colloca, Luana; Pine, Daniel S.; Ernst, Monique; Miller, Franklin G.; Grillon, Christian
Background Social cues and interpersonal interactions strongly contribute to evoke placebo effects that are pervasive in medicine and depend upon the activation of endogenous modulatory systems. Here we explore the possibility to boost placebo effects by targeting pharmacologically the vasopressin system, characterized by a sexually dimorphic response and involved in the regulation of human and nonhuman social behaviors. Methods We enrolled 109 healthy participants and studied the effects of intranasal administration of Avp1a and Avp1b arginine vasopressin receptor agonists against 1) no-treatment, 2) oxytocin, and 3) saline, in a randomized, placebo-controlled, double-blind, parallel design trial using a well-established model of placebo analgesia while controlling for sex differences. Results Vasopressin agonists boosted placebo effects in women but had no effect in men. The effects of vasopressin on expectancy-induced analgesia were significantly larger than those observed in the no-treatment (p<004), oxytocin (p<0.001) and saline (p<0.015) groups. Moreover, women with lower dispositional anxiety and cortisol levels showed the largest vasopressin-induced modulation of placebo effects, suggesting a moderating interplay between pre-existing psychological factors and cortisol changes. Conclusions This is the first study that demonstrates that arginine vasopressin boosts placebo effects and that the effect of vasopressin depends upon a significant sex by treatment interaction. These findings are novel and might open up new avenues for clinically relevant research due to the therapeutic potentials of vasopressin and oxytocin as well as the possibility to systematically control for influences of placebo responses in clinical trials. PMID:26321018
Gou, Kai-Jun; Zeng, Rui; Dong, Yan; Hu, Qi-Qi; Hu, Huang-Wan-Yin; Maffucci, Katherine G; Dou, Qi-Ling; Yang, Qing-Bo; Qin, Xu-Hua; Qu, Yan
Background and Purpose:Polygonum orientale L. (family: Polygonaceae), named Hongcao in China, is a Traditional Chinese Medicinal and has long been used for rheumatic arthralgia and rheumatoid arthritis. However, no pharmacological and mechanism study to confirm these clinic effects have been published. In this investigation, the anti-inflammatory, analgesic effects and representative active ingredient compounds of P. orientale have been studied. Methods: Dried small pieces of the stems and leaves of P. orientale were decocted with water and partitioned successively to obtain ethyl acetate and ethyl ether extract of P. orientale (POEa and POEe). Chemical compositions of them were analyzed by UPLC-Q-Exactive HRMS. Anti-inflammatory and analgesic effects of POEa and POEe were evaluated using xylene induced ear edema, carrageenan induced paw edema, Freunds' complete adjuvant induced arthritis, and formaldehyde induced pain in rat. Their mechanisms of anti-inflammatory and analgesic effects were also studied via assays of TNF-α, IL-1β, IL-6, and PGE2 in serum. Results: UPLC-Q-Exactive HRMS analysis showed that POEa and POEe mainly contained flavonoids including orientin, isoorientin, vitexin, luteolin, and quercetin. Furthermore, anti-inflammatory effects of POEa and POEe were evident in xylene induced ear edema. The paw edema in Freund's complete adjuvant and carrageenan were significantly (P < 0.05, 0.01) inhibited by POEa (5, 7.5 g/kg). POEe (7.5 g/kg) was significantly (P < 0.05, 0.01) inhibited Freunds' complete adjuvant induced paw edema and cotton pellet induced granuloma formation. Similarly, POEe significantly (P < 0.05, 0.01) inhibited the pain sensation in acetic acid induced writhing test. POEa (5, 7.5 g/kg) significantly (P < 0.05, 0.01) inhibited formaldehyde induced pain in both phases. POEa (7.5 g/kg) markedly (P < 0.05) prolonged the latency period of hot plate test after 30 and 60 min. The concentrations of TNF-α, IL-1β, IL-6, and PGE2 were
Guieu, R; Blin, O; Pouget, J; Serratrice, G
This study investigated whether indomethacin has an analgesic effect on the central nervous system. As analgesics which affect the central nervous system produce a correlated decrease in the subjective sensation of pain and in the nociceptive reflex in humans, the amplitude of the nociceptive flexion of the biceps femoris was studied. Eight patients (six men, two women) aged 35-70 years (mean 51) with rheumatic diseases were included in the study. Each patient was his or her own control and was given a single intramuscular injection of either 50 mg of indomethacin or a placebo. A placebo controlled, double blind experimental design was used. Patients were evaluated before and 30, 60, and 75 minutes after the injection. Seventy five minutes after injection, indomethacin gave a 54% decrease in the amplitude of the nociceptive reflex, whereas the placebo produced a decrease of only 12%. This suggests that indomethacin exerts a depressive effect on the amplitude of the nociceptive reflex and affects the central nervous system as part of its analgesic action. PMID:1575589
Otsuka, Fumio; Mizobuchi, Satoshi; Ogura, Toshio; Sato, Kenji; Yokoyama, Masataka; Makino, Hirofumi
We report the case of 19-year-old man with pituitary gigantism due to growth hormone-producing pituitary macroadenoma. The patient complained of recurrent headache and excessive growth spurt since age 15. Octreotide administration was initiated following transsphenoidal pituitary adenomectomy. Octreotide injection for 4 years efficaciously reduced the size of remnant adenoma as well as serum growth hormone levels. Notably, octreotide exhibited a potent analgesic effect on his intractable cluster headache that has continued even after reduction of the adenoma volume. The analgesic effect lasted 2 to 6 hours after each injection and no tachyphylaxis to octreotide appeared during 4-year treatment. To characterize the headache and the pain intensity, analgesic drugs including octreotide, lidocaine, morphine and thiopental were tested using a visual analogue scale (VAS) evaluation, with the result that octreotide exhibited a prompt and complete disappearance of the headache. Headache relief was in part reproduced by morphine injection (56% reduction) but not by lidocaine or thiopental. The present case suggests that the intractable headache associated with pituitary gigantism is possibly related to the endogenous opioid system. Thus, the headache control by octreotide is clinically helpful for continuation of the self-injection regimen.
Rivera-Arconada, Ivan; Roza, Carolina; Lopez-Garcia, Jose A
The spinal cord is the first relay center for nociceptive information. Following peripheral injury, the spinal cord sensitizes. A sign of spinal sensitization is the hyper-reflexia which develops shortly after injury and can be detected in the isolated spinal cord as a "memory of pain." In this context, it is easy to understand that many analgesic compounds target spinally located sites of action to attain analgesia. In vitro isolated spinal cord preparations have been used for a number of years, and experience on the effects of compounds of diverse pharmacological families on spinal function has accumulated. Recently, we have proposed that the detailed study of spinal segmental reflexes in vitro may produce data relevant to the evaluation of the analgesic potential of novel compounds. In this review, we describe the main features of segmental reflexes obtained in vitro and discuss the effects of compounds of diverse chemical nature and pharmacological properties on such reflexes. Our aim was to compare the different profiles of action of the compounds on segmental reflexes in order to extract clues that may be helpful for pharmacological characterization of novel analgesics. © 2015 John Wiley & Sons Ltd.
Matsuura, Wataru; Harada, Shinichi; Tokuyama, Shogo
Central post-stroke pain (CPSP), a potential sequela of stroke, is classified as neuropathic pain. Although we recently established a CPSP-like model in mice, the effects of adjuvant analgesics as therapeutic drugs for neuropathic pain in this model are unknown. Hence, the aim of the present study was to assess the usefulness of our model by evaluating the effects of adjuvant analgesics used for treating neuropathic pain in this mouse model of CPSP. Male ddY mice were subjected to 30 min of bilateral carotid artery occlusion (BCAO). The development of hind paw mechanical allodynia was measured after BCAO using the von Frey test. The mechanical allodynia was significantly increased on day 3 after BCAO compared with that during the pre-BCAO assessment. BCAO-induced mechanical allodynia was significantly decreased by intraperitoneal injections of imipramine (a tricyclic antidepressant), mexiletine (an antiarrhythmic), gabapentin (an antiepileptic), or a subcutaneous injection of morphine (an opioid receptor agonist) compared with that following vehicle treatment in BCAO-mice. By contrast, milnacipran (a serotonin and norepinephrine reuptake inhibitor), paroxetine (selective serotonin reuptake inhibitor), carbamazepine (antiepileptic), and indomethacin (nonsteroidal anti-inflammatory drug) did not affect the BCAO-induced mechanical allodynia. Our results show that BCAO in mice may be useful as an animal model of CPSP. In addition, BCAO-induced mechanical allodynia may be suppressed by some adjuvant analgesics used to treat neuropathic pain.
Rowlands, Dewi Kenneth; Cui, Yu Gui; So, Siu Cheung; Tsang, Lai Ling; Chung, Yiu Wa; Chan, Hsiao Chang
Dysmenorrhoea, defined as cramping pain in the lower abdomen occurring before or during menstruation, affects, to varying degrees, up to 90% of women of child-bearing age. We investigated whether BFP (Bak Foong Pills), a traditional Chinese medicine treatment for dysmenorrhoea, possesses analgesic properties. Results showed that BFP was able to significantly reduce pain responses following subchronic treatment for 3 days, but not following acute (1 h) treatment in response to acetic acid-induced writhing in C57/B6 mice. The analgesic effect was not due to inhibition of COX (cyclo-oxygenase) activity, evidenced by the lack of inhibition of prostacyclin and PGE2 (prostaglandin E2) production. Molecular analysis revealed that BFP treatment modulated the expression of a number of genes in the spinal cord of mice subjected to acetic acid writhing. RT-PCR (reverse transcription-PCR) analysis of spinal cord samples showed that both sst4 (somatostatin receptor 4) and sst2 receptor mRNA, but not μOR (μ-opiate receptor) and NK1 (neurokinin-1) receptor mRNA, were down-regulated following BFP treatment, thus implicating somatostatin involvement in BFP-induced analgesia. Administration of c-som (cyclo-somatostatin), a somatostatin antagonist, prior to acetic acid-induced writhing inhibited the analgesic effect. Thus subchronic treatment with BFP has anti-nociceptive qualities mediated via the somatostatin pathway.
Field, Tiffany; Diego, Miguel; Solien-Wolfe, Lynda
20 adults were randomly assigned to a massage therapy or a massage therapy plus a topical analgesic application group. Both groups received a weekly massage from a therapist and were taught self-massage (same procedure) to be done by each participant once daily over a four-week period. The massage plus topical analgesic group as compared to the massage group had greater improvement in hand function as measured by a digital hand exerciser following the first session and across the four-week period. That group also had a greater increase in perceived grip strength and a greater decrease in hand pain, depressed mood and sleep disturbances over the four-week period. Massage therapy has been effective for several pain syndromes including migraine headaches (Lawle and Cameron, 2006)), lower back pain (Hsieh et al., 2004), fibromyalgia (Kalichman, 2010), neck and shoulder pain (Kong et al., 2013), carpal tunnel syndrome (Elliott and Burkett, 2013), and pain related to upper limb arthritis (Field et al., 2013). The purpose of the current study was to determine whether applying a topical analgesic following massage might be more effective than massage alone in treating pain associated with hand arthritis. Copyright © 2013 Elsevier Ltd. All rights reserved.
Jelacic, Srdjan; Bollag, Laurent; Bowdle, Andrew; Rivat, Cyril; Cain, Kevin C; Richebe, Philippe
The authors hypothesized that intravenous acetaminophen as an adjunct analgesic would significantly decrease 24-hour postoperative opioid consumption. Double-blind, randomized, placebo-controlled trial. A single academic medical center. The study was comprised of 68 adult patients undergoing cardiac surgery. Patients were assigned randomly to receive either 1,000 mg of intravenous acetaminophen or placebo immediately after anesthesia induction, at the end of surgery, and then every 6 hours for the first 24 hours in the intensive care unit, for a total of 6-1,000 mg doses. The primary outcome was 24-hour postoperative opioid consumption. The secondary outcomes included 48-hour postoperative opioid consumption, incisional pain scores, opioid-related adverse effects, length of mechanical ventilation, length of intensive care unit stay, and the extent of wound hyperalgesia assessed at 24 and 48 hours postoperatively. The mean±standard deviation postoperative 24-hour opioid consumption expressed in morphine equivalents was significantly less in the acetaminophen group (45.6±29.5 mg) than in the placebo group (62.3±29.5 mg), representing a 27% reduction in opioid consumption (95% CI, 2.3-31.1 mg; p = 0.024). There were no differences in pain scores and opioid-related adverse effects between the 2 groups. A significantly greater number of patients in the acetaminophen group responded "very much" and "extremely well" when asked how their overall pain experience met their expectation (p = 0.038). The administration of intravenous acetaminophen during cardiac surgery and for the first 24 hours postoperatively reduced opioid consumption and improved patient satisfaction with their overall pain experience but did not reduce opioid side effects. Copyright © 2016 Elsevier Inc. All rights reserved.
Kane, F M A; Brodie, E E; Coull, A; Coyne, L; Howd, A; Milne, A; Niven, C C; Robbins, R
Vascular wounds may require frequent dressing changes over a long period of time, often involving pain, which may not be adequately controlled with conventional analgesia. Complementary analgesia may be beneficial as an adjunctive therapy. This pilot study presented eight patients with two odour therapies, lavender and lemon, two music therapies, relaxing and preferred music and a control condition, during vascular wound dressing changes. Although the therapies did not reduce the pain intensity during the dressing change there was a significant reduction in pain intensity for the lavender therapy and a reduction in pain intensity for the relaxing music therapy after the dressing change. This supports the use of these complementary therapies, which are inexpensive, easy to administer and have no known side effects, as adjunctive analgesia in this patient population. Earlier administration before dressing change may enhance these effects. Further research is required to ascertain why certain complementary therapies are more effective than others at relieving pain.
Chowdhury, Saikat; Nishteswar, K.; Nariya, Mukesh Kumar
Background: Herbal analgesic and anti-inflammatory remedies are preferred much because of lesser side effects and also a lower tendency for habit formation. Pentatropis capensis is such an analgesic and anti-inflammatory drug which is popular among folklore remedies for various injuries and inflammatory problems. It is called by the name of Kākanāsikā in Ayurvedic works. This study was designed to investigate the analgesic, and anti-inflammatory effects of aqueous extract of P. capensis leaves (AEPC) in rats. Materials and Methods: AEPC was assessed for Analgesic effect through radiant heat tail-flick model and anti-inflammatory effect through carrageenan-induced paw edema model on Wistar strain of albino rats. Results: Pentatropis capensis leaves aqueous extract showed significant (P < 0.001) increase in the duration of latency of tail flick response at the dose levels of 450 mg/kg, p.o. as compared to the control group. Similarly, the similar dose level produced significant (P < 0.01) anti-inflammatory effect against acute paw edema after 3 h of carrageenan induction when compared to the control group. Conclusion: The observed effects were comparable with the standard drug-treated group thus demonstrating effective central analgesic and acute anti-inflammatory potentials of the P. capensis leaves aqueous extract and the observations substantiate its folklore use as an analgesic and anti-inflammatory. PMID:25861138
Wright, M; McGrath, C J
Two acupuncture regimens were compared as to their efficacy in inducing analgesia sufficient for midline abdominal incisions in dogs. In addition, the physiologic effects of electrostimulation of the single point that the 2 regimens had in common, Tsu-san-li (stomach or St-36), were examined. The physiologic effects were compared with those monitored during the procedure used for induction of analgesia. Electrostimulation of 1 acupoint combination, St-36 and Yang-ling-chuan (gallbladder or GB-34), induced effective analgesia for an abdominal midline incision in 8 of 9 dogs tested (89%). The second point combination, St-36 and San-yin-chiao (spleen or Sp-6), induced effective analgesia for an abdominal midline incision in only 2 of 8 dogs tested (25%). Analgesia was inferred when an animal's struggling response during the incision procedure was absent or minimal. Heart rate, respiratory rate, and arterial blood pressure were monitored during acupoint stimulation. Significant changes in heart rate or respiratory rate were not detected during electrostimulation of St-36, St-36 and GB-34, or randomly selected nonacupuncture metatarsal loci. Although there were statistically significant decreases in systolic blood pressure during electrostimulation of nonacupuncture points alone and of St-36 alone, the magnitude of these increases was small, ranging from 3.75 mm of Hg to 4 mm of Hg.
Oh, Eunjung; Ahn, Hyun Joo; Sim, Woo Seog; Lee, Jin Young
An intravenous form of ibuprofen has recently been approved by the Food and Drug Administration (FDA) and reports are rare on its co-administration with opioids. We researched whether an intravenous ibuprofen-hydromorphone combination is synergistic, additive, or infra-additive on postoperative pain. A parallel-group, 1:1:1 allocation, randomized, double-blind controlled trial. University teaching hospital in Korea. Ninety patients, undergoing breast surgery, were divided into one of the 3 groups (I, H, IH groups). Positive analgesic efficacy was defined as a numeric rating scale (NRS)= 3 on a 0 - 10 NRS, 30 minutes after the drug administration. Drugs were administered by the Dixon's up-and-down method. Starting doses were ibuprofen (I) 50 mg, hydromorphone (H) 0.25 mg, or ibuprofen 25 mg + hydromorphone 0.125 mg (IH). The maximum doses were ibuprofen 800 mg, hydromorphone 2 mg, or ibuprofen 400 mg + hydromorphone 1 mg. Combination index (CI) (additive: 0.9 - 1.1, synergism: < 0.9, antagonism: > 1.1), dose reduction index (DRI, a measure of how much the dose of each drug in a combination can be reduced), and isobologram were used to define the nature of their interaction. One way ANOVA, Kruskal Wallis test, and Chi square test, significance level P < 0.05. The median effective doses (ED50) of ibuprofen and hydromorphone were 1,447 mg and 1.5 mg, respectively. The median ED50 of the combination was ibuprofen 71 mg and hydromorphone 0.3 mg. Ibuprofen and hydromorphone showed a strong synergy (CI 0.2, DRI 20 and 5 for ibuprofen and hydromorphone at ED50). Analgesic efficacy was observed during post-anesthesia care unit (PACU) period only. The combination of intravenous ibuprofen and hydromorphone produces a strong synergistic analgesia on postoperative pain.
Dilmen, Ozlem Korkmaz; Akcil, Eren Fatma; Tunali, Yusuf; Karabulut, Esra Sultan; Bahar, Mois; Altindas, Fatis; Vehid, Hayriye; Yentur, Ercument
The prevalence of moderate to severe pain is high in patients following craniotomy. Although optimal analgesic therapy is mandatory, there is no consensus regarding analgesic regimen for post-craniotomy pain exists. This study aimed to investigate the effects of morphine and non-opioid analgesics on postcraniotomy pain. This prospective, randomized, double blind, placebo controlled study included eighty three patients (ASA 1, II, and III) scheduled for elective supratentorial craniotomy. Intravenous dexketoprofen, paracetamol and metamizol were investigated for their effects on pain intensity, morphine consumption and morphine related side effects during the first 24h following supratentorial craniotomy. Patients were treated with morphine based patient controlled analgesia (PCA) for 24h following surgery and randomized to receive supplemental IV dexketoprofen 50mg, paracetamol 1g, metamizol 1g or placebo. The primary endpoint was pain intensity, secondary endpoint was the effects on morphine consumption and related side effects. When the whole study period was analyzed with repeated measures of ANOVA, the pain intensity, cumulative morphine consumption and related side effects were not different among the groups (p>0.05). This study showed that the use of morphine based PCA prevented moderate to severe postoperative pain without causing any life threatening side effects in patients undergoing supratentorial craniotomy with a vigilant follow up during postoperative 24h. Although we could not demonstrate statistically significant effect of supplemental analgesics on morphine consumption, it was lower in dexketoprofen and metamizol groups than control group. Copyright © 2016 Elsevier B.V. All rights reserved.
Ebneshahidi, Amin; Mohseni, Masood
After cesarean section surgery, routine pharmacologic methods of analgesia--opioids and benzodiazepines--may impair the immediate close contact of mother and neonate for their sedative and emetic effects. The aim of this study was to explore the effect of patient-selected music on postoperative pain, anxiety, opioid requirement, and hemodynamic profile. A total of 80 patients, American Society of Anesthesiologists (ASA) physical status I-II, scheduled to undergo general anesthesia and elective cesarean section surgery were enrolled. Patients were randomly allocated to receive 30 minutes of music or silence via headphones postoperatively. Pain and anxiety were measured with a visual analogue scale. Total postoperative morphine requirement as well as blood pressure and heart rate were recorded after the intervention period. Pain score and postoperative cumulative opioid consumption were significantly lower among patients in the music group (p < 0.05), while there were no group differences in terms of anxiety score, blood pressure, or heart rate (p > 0.05). Postoperative use of patient-selected music in cesarean section surgery would alleviate the pain and reduce the need for other analgesics, thus improving the recovery and early contact of mothers with their children.
Ferrari, Renata; Zanolin, Maria E; Duse, Genni; Visentin, Marco
There is general agreement about the need to perform a screening test to assess the risk of opioid misuse prior to starting a long-term opioid treatment for chronic noncancer pain. The evidence supporting the effectiveness of opioid long-term treatment is weak, and no predictors of its usefulness have been assessed. The aim of this study was to assess the effect on pain and quality of life of chronic opioid treatment, and detect the possible predictors of its effectiveness. This observational, prospective study was conducted in 2 Italian Pain Relief Units on 77 patients affected by intractable chronic pain. Patients were submitted to psycho-logical tests, investigating the individual pain experience, risk of opioid misuse, mood states, quality of life, and personality characteristics prior to starting treatment and at 2,4, and 6-month follow-up. Both maximum and habitual pain, as measured with VAS, underwent a statistically significant reduction at 2, 4, and 6-month follow-up. In multivariate analysis, lower scores in the Pain Medication Questionnaire (PMQ) were predictive of a major reduction in maximum VAS (P = 0.005). Both low PMQ and MMPI-cynicism scores were predictive of habitual VAS decrease (P = 0.012 and P = 0.028, respectively). The results indicate that pain relief significantly improved over a 6-month period of opioid treatment, together with quality of life. The outcome was better in patients with a pretreatment low risk of opioid misuse, low scores in the Cynicism scale of MMPI-2, and no aberrant drug behaviors at follow-up. Therefore, a psychological screening and support is crucial for a good outcome of opioid therapy for chronic noncancer pain patients.
Pain is a widespread symptom in clinical practice. Older adults and chronically ill patients are particularly affected. In multimorbid geriatric patients, pharmacological pain treatment is an extension of a previously existing multimedication. Besides the efficacy of pain treatment, drug side effects and drug-drug interactions have to be taken into account to minimize the health risk for these patients. Apart from the number of prescriptions, the age-related pharmacokinetic and pharmacodynamic changes significantly increase the risk among older adults. The use of non-steroidal anti-inflammatory drugs (NSAID) is widespread but NSAIDs have the highest risk of adverse drug reactions and drug interactions. In particular, the gastrointestinal, cardiovascular, renal and coagulation systems are affected. Apart from the known toxic effect on the liver (in high doses), paracetamol (acetaminophen) has similar risks although to a lesser degree. According to current data, metamizol is actually better than its reputation suggests. The risk of potential drug interactions seems to be low. Apart from the risk of sedation in combination with other drugs, tramadol and other opioids can induce the serotonin syndrome. Among older adults, especially in the case of polypharmacy, an individualized approach should be considered instead of sticking to the pain management recommended by the World Health Organization (WHO) in order to minimize drug-drug interactions and adverse drug reactions.
(1) When oral morphine does not relieve severe pain and when there is no specific treatment for the underlying cause, the first option is to try subcutaneous or intravenous administration. If this standard treatment fails or is poorly tolerated, intrathecal injection is usually preferred as the direct route to the central nervous system. However, one-quarter to one-half of patients still do not achieve adequate pain relief, and adverse effects are relatively frequent; (2) Ziconotide is not an opiate and is not related to the usual classes of drugs that interfere with nervous transmission in the posterior horn of the spinal cord. Marketing authorization has been granted for "severe, chronic pain in patients who require intrathecal analgesia". The Summary of Product Characteristics (SPC) recommends continuous infusion via an intrathecal catheter connected to a pump; (3) Clinical evaluation of ziconotide does not include any trials versus morphine in patients with nociceptive pain, or any trials versus tricyclic or antiepileptic drugs in patients with neurogenic pain; (4) In a trial in 220 patients in whom systemic morphine had failed, the mean pain score on a 100-mm visual analogue scale was 69.8 mm after three weeks on ziconotide, compared to 75.8 mm with placebo. This difference, although statistically significant, is clinically irrelevant. The proportion of "responders" (reduction of at least 30% in the initial pain score) was respectively 16.1% and 12.0% (no statistically significant difference); (5) The two other placebo-controlled trials included 112 patients with pain linked to cancer or HIV infection, and 257 patients with non-cancer pain. After a titration phase lasting 5 to 6 days, a combined analysis of the two trials showed that the mean pain score was 48.8 mm with ziconotide and 68.4 mm with placebo (statistically significant difference). However, many patients did not complete the titration phase. Efficacy also appeared to differ according to the type
To determine if there is a relationship between the risk of postoperative complications and the nonclinical hospital characteristics of bed size, ownership structure, relative urbanicity, regional location, teaching status, and area income status. This study involved a secondary analysis of 2006 administrative hospital data from a number of U.S. states. This data, gathered annually by the Agency for Healthcare Research and Quality (AHRQ) via the National Inpatient Sample (NIS) Healthcare Utilization Project (HCUP), was analyzed using probit regressions to measure the effects of several nonclinical hospital categories on seven diagnostic groupings. The study model included postoperative complications as well as additional potentially confounding variables. The results showed mixed outcomes for each of the hospital characteristic groupings. Subdividing these groupings to correspond with the HCUP data analysis allowed a greater understanding of how hospital characteristics' may affect postoperative outcomes. Nonclinical hospital characteristics do affect the various postoperative complications, but they do so inconsistently.
Background Propofol is a good induction agent, but it has the disadvantage of causing pain on intravenous injection. The incidence of propofol-induced pain is approximately 70%. Palonosetron is a novel second-generation 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist. We presumed that palonosetron would be effective in reducing the occurrence of propofol-induced pain based on similar mechanisms to other 5-HT3 receptor antagonists. Methods Eighty patients were randomized to either Group N (0.9% sodium chloride [normal saline] 2 ml, n = 40) or Group P (palonosetron 0.075 mg, 2 ml, n = 40). Patients were intravenously given a 2 ml pretreatment solution, containing either palonosetron 0.075 mg or normal saline. Following pretreatment with 2 ml of palonosetron 0.075 mg or normal saline, we manually occluded venous drainage midarm with the help of an assistant. One minute later, we released the occlusion of venous drainage. This was followed by a 5-second propofol injection at 25% of the total calculated doses. Patients were then interviewed about whether or not they experienced propofol-induced pain. Results Overall, the incidence of propofol-induced pain was 60% in the normal saline group and 27.5% in the palonosetron group. No patients in the palonosetron group experienced severe pain. The incidence of propofol-induced pain was significantly lower in the palonosetron group compared to the normal saline group (P < 0.01). Conclusions Following pretreatment with palonosetron, 72.5% of patients experienced a decrease in the occurrence of propofol-induced pain. PMID:24624266
Debono, Bertrand; Bousquet, Philippe; Sabatier, Pascal; Plas, Jean-Yves; Lescure, Jean-Paul; Hamel, Olivier
The rise of eHealth, with the increasing use of a Mobile application provides a new perspective for outpatient spine surgery follow-up. Assess the feasibility of Mobile app for postoperative monitoring after outpatient lumbar discectomy. Sixty consecutive patients, who underwent an ambulatory lumbar discectomy, were proposed the use of Mobile app to optimize their home monitoring for 15 days. Contact was maintained with the clinic based on the level of symptom severity: pain, temperature, deficit, bleeding, to provide a suitable solution. Use of Mobile app compared to the standard follow-up procedure was evaluated daily and a satisfaction survey was carried-out 3 months after surgery. Thirty-six patients (60.0 %) completed the initial checklist within 48 h, with no triggered severity. Five patients (8.3 %) triggered a non-response alarm; no action was required in the follow-up of 41 patients. However, 19 patients (31.7 %) triggered a total of 29 alarms, automatically resulting in a neurosurgeon contact for: postoperative pain management and optimization of analgesics, 21 cases (72.4 %), low-grade fever <38.5°, 4 cases (13.8 %), voiding delay, 2 cases (6.9 %) and a problem related to dressing, 2 cases (6.9 %). The scale ranged from 1 (poor) to 4 (excellent), with a 3.5/4 overall satisfaction mean score for the mobile handheld-device. Most patients (91.6 %) responded that they would agree to repeat the postoperative experience. Overall patient satisfaction was excellent. Mobile app provides an effective useful tool for outpatient spine surgery monitoring and minimizes the need for in-person visits for postoperative patients.
Rost, A; Schenck, E G
In 60 young, healthy volunteers the analgesic efficacy of 1-(m-methoxyphenyl)-2-(dimethylaminomethyl)-cyclohexan-1-ol (tramadol; Tramal), dextropropoxyphene and a commercial drug mixture (acetylsalicylic acid 200 mg; phenacetin 200 mg; codeine phosphor. 10 mg; caffeine anhydr. 50 mg; phenobarbital 25 mg) was investigated by determining the pain threshold in dental pulp. All three drugs increased the pain threshold considerably but there was no difference in the analgesic effect of the three drugs.
Saryazdi, Hamid Hajigholam; Aghadavoudi, Omid; Shafa, Amir; Masoumi, Amin; Saberian, Parnian
Postoperative pain due to tissue damage caused during surgery not only causes discomfort for the patients, but can also result in prolonged hospitalization, increased morbidity and respiratory disorders, and readmission to the hospital. For postoperative pain control, numerous methods and medications have been suggested, such as non-steroidal anti-inflammatory drugs (NSAIDs) and narcotics. Pethidine, as a narcotic analgesic, and ketorolac, as an NSAID, are widely used for pain control. Thus, in this study, the effects of these two drugs were studied and compared in terms of pain control after inguinal hernia surgery in children of 1-12 years of age. Sixty-six children undergoing inguinal herniorrhaphy were selected and randomly divided into 2 groups. The first group received 0.5 mg/kg ketorolac and the second group received 1 mg/kg pethidine during extubation. Postoperative pain (using Wong Baker pain scale) and complications were measured until 24 hours after surgery. Mean and standard deviations of postoperative pain 1 hour after surgery in the pethidin and ketorolac groups were 5.06 ± 1.41 and 3.88 ± 0.93, respectively. The scale was significantly lower in the ketorolac group (P < 0.001). Postoperative pain intensity 2 hours after surgery in these two groups was 4.48 ± 1.52 and 3.55 ± 1.15, respectively, and the difference between the two groups was significant (P = 0.006). The variation in postoperative pain intensity in the ketorolac group was statistically lower than the pethidin group (P = 0.020). CONCLUSION.
Fentanyl is the most commonly used opioid analgesic in intravenous patient-controlled analgesia (IV PCA) in Korea. IV oxycodone was approved for postoperative IV PCA by the Ministry of Food and Drug Safety of Korea in 2013. The approved dosage regimen for postoperative pain relief with IV oxycodone is IV bolus loading of 2 mg followed by PCA composed of demand boluses of 1 mg and no background infusion with an oxycodone concentration of 1 mg/ml. However, a simulation study indicated that the minimum effective analgesic concentration (MEAC, as indicated by relief of pain by administering rescue analgesics) of oxycodone was reached most quickly with a higher loading dose of 0.1 mg/kg and IV PCA with background infusion. Oxycodone is a therapeutic option as an analgesic for postoperative pain management. It is necessary to reduce the analgesic dose of oxycodone in elderly patients because metabolic clearance decreases with age. PMID:27274364
Fifty to 75% of patients report that postoperative pain management is grossly inadequate. A contributing factor to this analgesic deficit may be...produces hyperalgesia. Ketamine, an NMDA receptor antagonist, administered preemptively may inhibit central sensitization and thereby reduce postoperative ...2 factorial, double blind, placebo- controlled study, 37 female and 18 male (N =55) ASA 1-3 participants who underwent elective laparoscopic surgery
Cooper, Ziva D; Comer, Sandra D; Haney, Margaret
Recent studies have demonstrated the therapeutic potential of cannabinoids to treat pain, yet none have compared the analgesic effectiveness of smoked marijuana to orally administered Δ(9)-tetrahydrocannabinol (THC; dronabinol). This randomized, placebo-controlled, double-dummy, double-blind study compared the magnitude and duration of analgesic effects of smoked marijuana and dronabinol under well-controlled conditions using a validated experimental model of pain. Healthy male (N=15) and female (N=15) daily marijuana smokers participated in this outpatient study comparing the analgesic, subjective, and physiological effects of marijuana (0.00, 1.98, or 3.56% THC) to dronabinol (0, 10, or 20 mg). Pain response was assessed using the cold-pressor test (CPT): participants immersed their left hand in cold water (4 °C), and the time to report pain (pain sensitivity) and withdraw the hand from the water (pain tolerance) were recorded. Subjective pain and drug effect ratings were also measured as well as cardiovascular effects. Compared with placebo, marijuana and dronabinol decreased pain sensitivity (3.56%; 20 mg), increased pain tolerance (1.98%; 20 mg), and decreased subjective ratings of pain intensity (1.98, 3.56%; 20 mg). The magnitude of peak change in pain sensitivity and tolerance did not differ between marijuana and dronabinol, although dronabinol produced analgesia that was of a longer duration. Marijuana (1.98, 3.56%) and dronabinol (20 mg) also increased abuse-related subjective ratings relative to placebo; these ratings were greater with marijuana. These data indicate that under controlled conditions, marijuana and dronabinol decreased pain, with dronabinol producing longer-lasting decreases in pain sensitivity and lower ratings of abuse-related subjective effects than marijuana.
Jahromi, S Abbas Hosseini; Valami, S Massumeh Hosseini; Yaghoubi, Siamak
The main problem in the postoperative period is pain relief. Adequate postoperative analgesia not only leads to patient's comfort but also decreases morbidity, nursing care and time of hospitalization. Determination of the effect of intraperitoneal pethidine on postoperative pain in women scheduled for elective tubal ligation was undertaken. In a double blind clinical trial study of 60 women, ASA I, 25-45 years old, were enrolled for elective tubal ligation in Kosar hospital in Qazvin, IRAN. Patients were randomly divided in two equal groups (30 each).One group received pethidine intraperitoneally and the other group received equal amount of placebo in the same region. The intensity of postoperative pain was evaluated by visual analogue scale (VAS) for about 8 hours. Incidence of nausea was also evaluated. Data was transformed to SPSS software. Then data analysis was performed by U-test. There was no significant statistical difference with regard to age, weight, and time of operation between the two groups. The mean score of pain was significantly lower in intraperitoneal pethidine group than placebo group but the incidence of nausea in the intraperitoneal pethidine group was more than in placebo group (P < 0.05). Thus, intraperitoneal pethidine decreases postoperative pain but increases postoperative nausea.
Largent-Milnes, T M; Brookshire, S W; Skinner, D P; Hanlon, K E; Giuvelis, D; Yamamoto, T; Davis, P; Campos, C R; Nair, P; Deekonda, S; Bilsky, E J; Porreca, F; Hruby, V J; Vanderah, T W
The most highly abused prescription drugs are opioids used for the treatment of pain. Physician-reported drug-seeking behavior has resulted in a significant health concern among doctors trying to adequately treat pain while limiting the misuse or diversion of pain medications. In addition to abuse liability, opioid use is associated with unwanted side effects that complicate pain management, including opioid-induced emesis and constipation. This has resulted in restricting long-term doses of opioids and inadequate treatment of both acute and chronic debilitating pain, demonstrating a compelling need for novel analgesics. Recent reports indicate that adaptations in endogenous substance P/neurokinin-1 receptor (NK1) are induced by chronic pain and sustained opioid exposure, and these changes may contribute to processes responsible for opioid abuse liability, emesis, and analgesic tolerance. Here, we describe a multifunctional mu-/delta-opioid agonist/NK1 antagonist compound [Tyr-d-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-Bn(CF3)2 (TY027)] that has a preclinical profile of excellent antinociceptive efficacy, low abuse liability, and no opioid-related emesis or constipation. In rodent models of acute and neuropathic pain, TY027 demonstrates analgesic efficacy following central or systemic administration with a plasma half-life of more than 4 hours and central nervous system penetration. These data demonstrate that an innovative opioid designed to contest the pathology created by chronic pain and sustained opioids results in antinociceptive efficacy in rodent models, with significantly fewer side effects than morphine. Such rationally designed, multitargeted compounds are a promising therapeutic approach in treating patients who suffer from acute and chronic pain.
Largent-Milnes, T. M.; Brookshire, S. W.; Skinner, D. P.; Hanlon, K. E.; Giuvelis, D.; Yamamoto, T.; Davis, P.; Campos, C. R.; Nair, P.; Deekonda, S.; Bilsky, E. J.; Porreca, F.; Hruby, V. J.
The most highly abused prescription drugs are opioids used for the treatment of pain. Physician-reported drug-seeking behavior has resulted in a significant health concern among doctors trying to adequately treat pain while limiting the misuse or diversion of pain medications. In addition to abuse liability, opioid use is associated with unwanted side effects that complicate pain management, including opioid-induced emesis and constipation. This has resulted in restricting long-term doses of opioids and inadequate treatment of both acute and chronic debilitating pain, demonstrating a compelling need for novel analgesics. Recent reports indicate that adaptations in endogenous substance P/neurokinin-1 receptor (NK1) are induced by chronic pain and sustained opioid exposure, and these changes may contribute to processes responsible for opioid abuse liability, emesis, and analgesic tolerance. Here, we describe a multifunctional mu-/delta-opioid agonist/NK1 antagonist compound [Tyr-d-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-Bn(CF3)2 (TY027)] that has a preclinical profile of excellent antinociceptive efficacy, low abuse liability, and no opioid-related emesis or constipation. In rodent models of acute and neuropathic pain, TY027 demonstrates analgesic efficacy following central or systemic administration with a plasma half-life of more than 4 hours and central nervous system penetration. These data demonstrate that an innovative opioid designed to contest the pathology created by chronic pain and sustained opioids results in antinociceptive efficacy in rodent models, with significantly fewer side effects than morphine. Such rationally designed, multitargeted compounds are a promising therapeutic approach in treating patients who suffer from acute and chronic pain. PMID:23860305
Eftekharian, Hamid Reza; Ilkhani pak, Homa
Objective: To evaluate the effects of intravenous ketorolac on early postoperative pain in patients with mandibular fractures, who underwent surgical repair. Methods: This prospective, randomized, placebo-controlled clinical trial was conducted in Shahid Rajaei Hospital, affiliated with Shiraz University of Medical Sciences during a 1-year period from 2015 to 2016. We included a total number of 50 patients with traumatic mandibular fractures who underwent surgical repair. Patients with obvious contraindications to ketorolac such as asthma, renal dysfunction, peptic ulceration, bleeding disorders, cardiovascular disease, mental retardation, or allergy to ketorolac or NSAIDS, were excluded. The patients were randomly assigned to receive intravenous ketorolac (30 mg) at the end of operation in post anesthesia care unit immediately upon the onset of pain (n=25), or intravenous distilled water as placebo (n=25). Postoperative monitoring included non-invasive arterial blood pressure, ECG, and peripheral oxygen saturation. The postoperative pain was evaluated by a nurse using visual analog scale (VAS) (0–100 mm) pain score 4 hours after surgery and was compared between the two study groups. Results: Overall we included 50 patients (25 per group) in the current study. The baseline characteristics including age, gender, weight, operation duration, anesthesia duration and type of surgical procedure were comparable between two study groups. Those who received placebo had significantly higher requirements for analgesic use compared to ketorolac group (72% vs. 28%; p=0.002). Ketorolac significantly reduced the pain intensity 30-min after the operation (p<0.001). There were no significant side effects associated with ketorolac. Conclusion: Intravenous single-dose ketorolac is a safe and effective analgesic agent for the short-term management of mild to moderate acute postoperative pain in mandibular fracture surgery and can be used as an alternative to opioids. PMID:28246618
Domiati, Souraya; El-Mallah, Ahmed; Ghoneim, Asser; Bekhit, Adnan; El Razik, Heba Abd
Non-steroidal anti-inflammatory drugs are associated with several side effects, such as gastrointestinal mucosal damage, renal toxicity, and cardiovascular side effects. Aiming to find a novel analgesic/anti-inflammatory drug with minimal side effects, the present study was designed to screen and evaluate some newly synthesized pyrazole derivatives. Anti-inflammatory activity using carrageenan-induced rat paw edema and cotton-pellet-induced granuloma, COX-1/COX-2 selectivity using thin layer chromatography, and analgesic using hot plate and tail flick tests as well as ulcerogenic and renal side effects of the ten compounds were assessed. The results of the carrageenan-induced rat paw edema showed that the carboxyphenylhydrazone derivative (N9) was more potent than the chlorophenyl counterpart (N8) with a relative activity compared to celecoxib of 1.08 and -0.13, respectively, after 1 h. Even though this is true, N9 caused significant increase in the ulcer index, creatinine, and Blood Urea Nitrogen levels. The cotton granuloma test showed that the carboxyphenylhydrazone derivative (N7) was also more potent than its chlorophenyl counterpart (N6) with a relative activity compared to celecoxib of 1.13 and 0.86, respectively. Moreover, adding an acetyl not only increased the anti-inflammatory activity from a relative activity compared to celecoxib of 0.57-1.17 for the compounds X4 and N5, respectively, in the granuloma test, but also increased the selectivity toward COX-2 from 0.197 to 47.979. As a conclusion, from the ten compounds analyzed, N5 and N7 showed promising results as anti-inflammatory/analgesic agents with low ulcerogenicity and nephrotoxicity and thus should be further analyzed to determine the ED50 and other side effects.
Fatemeh Kazempor, Seyedeh; Vafadar langehbiz, Shabnam; Hosseini, Mahmoud; Naser Shafei, Mohammad; Ghorbani, Ahmad; Pourganji, Masoomeh
Regarding the effects of Coriandrum sativum (C. sativum) on central nervous system, in the present study analgesic properties of different extracts of C. sativum aerial partswere investigated. The mice were treated by saline, morphine, three doses (20, 100 and 500 mg/kg) of aqueous, ethanolic, choloroformic extracts of C. sativum and one dose (100 mg/kg) of aqueous, two doses of ethanolic (100 and 500 mg/kg) and one dose of choloroformic (20 mg/kg) extracts of C. sativum pretreated by naloxone. Recording of the hot plate test was performed 10 min before injection of the drugs as a base and it was consequently repeated every 10 minutes after the extracts injection. The maximal percent effect (MPE) in the groups treated by three doses of aqueous, ethanolic and chloroformic extracts were significantly higher than saline group which were comparable to the effect of morphine. The effects of most effective doses of extracts were reversed by naloxone. The results of present study showed analgesic effect of aqueous, ethanolic and chloroformic extracts of C. sativum extract. These effects of the extracts may be mediated by opioid system. However, more investigations are needed to elucidate the exact responsible mechanism(s) and the effective compound(s).
Leung, Jacqueline M.; Sands, Laura P.; Lim, Eunjung; Tsai, Tiffany L.; Kinjo, Sakura
Objectives To investigate whether preoperative risk for delirium moderates the effect of postoperative pain and opioids on the development of postoperative delirium. Design Prospective cohort study Setting University medical center Participants Patients ≥ 65 years of age scheduled for major noncardiac surgery Measurements A structured interview was conducted pre- and post-operatively to determine the presence of delirium, defined using the Confusion Assessment Method. We first developed a prediction model to determine which patients were at high vs. low risk for the development of delirium based on preoperative patient data. We then computed a logistic regression model to determine whether preoperative risk for delirium moderates the effect of postoperative pain and opioids on incident delirium. Results Of 581 patients, 40% developed delirium on days 1 or 2 after surgery. Independent preoperative predictors of postoperative delirium included lower cognitive status, a history of central nervous system disease, high surgical risk, and major spine and joint arthroplasty surgery. Compared to the patients at low preoperative risk for developing delirium, the relative risk for postoperative delirium for those in the high preoperative risk group was 2.38 (95% CI = 1.67–3.40). A significant three-way interaction indicates that preoperative risk for delirium significantly moderated the effect of postoperative pain and opioid use on the development of delirium. Among patients at high preoperative risk for development of delirium who also had high postoperative pain and received high opioid doses, the incidence of delirium was 72%, compared to 20% among patients with low preoperative risk, low postoperative pain and received low opioid doses. Conclusions High levels of postoperative pain and using high opioid doses increased risk for postoperative delirium for all patients. However, the highest incidence of delirium was among patients who had high preoperative risk for
O'Neill, Jennifer; Helwig, Elizabeth
Spinal anesthesia is a common regional anesthesia used in ambulatory and hospital settings. Spinal anesthesia has been shown to reduce postoperative pain and morbidity in certain populations. Understanding the physiological changes during spinal anesthesia can help predict and manage side effects including hypotension, bradycardia, decreased expiration, nausea, vomiting, and urinary retention. This article describes the physiological effects of spinal anesthesia in a body systems approach, describes how to assess the spinal level, and presents common side effects seen postoperatively and how to successfully manage and treat these patients. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.
Borazan, Hale; Tuncer, Sema; Yalcin, Naime; Erol, Atilla; Otelcioglu, Seref
Our intention was to assess the effectiveness of preoperative oral melatonin medication on sedation, sleep quality, and postoperative analgesia in patients undergoing elective prostatectomy. Fifty-two ASA I-II patients undergoing elective prostatectomy were included in this study, randomly divided into two groups. Patients received an oral placebo (n = 26) or 6 mg melatonin (n = 26) the night before and 1 h before surgery. All patients received a standard anesthetic protocol. At the end of surgery, all patients received tramadol i.v. via a PCA device. Extubation time, intraoperative fentanyl consumption, and recovery time were assessed at the end of the operation. Pain scores, tramadol consumption, and sedation scores were assessed at 1, 2, 4, 6, 12, 18, and 24 h postoperatively, and sleep quality and subjective analgesic efficacy were assessed at 24 h after surgery. There were no significant differences in demographic data between the groups. Extubation time and recovery time from anesthesia were significantly longer in the melatonin group (P < 0.05). Intraoperative fentanyl usage, pain scores, and tramadol consumption were significantly lower in the melatonin group (P < 0.05). The postoperative sleep quality of patients was significantly better in the melatonin group than in the control group (P < 0.05). Postoperative VAS of pain was significantly lower in the melatonin group compared with the control group at 1, 2, 4, 6, 12, 18, and 24 h postoperatively (P < 0.05). Subjective analgesic efficacy of patients was significantly different between groups (P < 0.05). The sedation scores were significantly higher in the melatonin group than in the control group at 1 h and 2 h after surgery (P < 0.05). Preoperative oral melatonin administration decreased pain scores and tramadol consumption and enhanced sleep quality, sedation scores, and subjective analgesic efficacy during the postoperative period.
Kuru, Serdar; Bozkirli, Osman Bahadir; Barlas, Aziz Mutlu; Duymus, Mehmet Esat; Senes, Mehmet; Yumusak, Nihat; Yilmaz, Cevdet; Kismet, Kemal
This study aimed to determine the possible preventive effects of dexmedetomidine on postoperative intra-abdominal adhesions. Dexmedetomidine is a highly selective and potent α2 adrenergic agonist with sedative, analgesic, anxiolytic, sympatholytic, hemodynamic, and diuretic properties. In recent years, investigations have shown that dexmedetomidine possesses secondary antioxidant and also anti-inflammatory effects. Thirty Wistar albino male rats were randomized and divided into 3 groups of 10 animals each: group 1, sham-operated; group 2, cecal abrasion + peritoneal dissection; group 3, cecal abrasion + peritoneal dissection followed by daily intravenous injection of 10 μg/kg dexmedetomidine for 10 days. The animals were killed on postoperative day 21. Blood and cecal samples were taken for biochemical and histopathologic evaluation. In this study, biochemical and pathologic parameters were significantly better in the cecal abrasion + peritoneal dissection + dexmedetomidine group when compared with the cecal abrasion + peritoneal dissection group. Tissue malondialdehyde, myeloperoxidase, total sulfhydryl, and catalase were found to be significantly different between the cecal abrasion/peritoneal dissection + dexmedetomidine and the cecal abrasion/peritoneal dissection groups. Plasma malondialdehyde and total sulfhydryl values were also statistically different between these groups (P < 0.05). Statistical analyses of mean pathologic scores showed that the histopathologic damage in the cecal abrasion/peritoneal dissection + dexmedetomidine group was significantly less than the damage in the control group (P < 0.05 for all pathologic parameters). The results of this study show that dexmedetomidine had a significant preventive effect on postoperative intra-abdominal adhesions. We concluded that these effects might be due to antioxidant and anti-inflammatory activities. PMID:25594644
Lee, Jae Jin; Lee, Mi Kyoung; Lim, Byung Gun; Hur, Wonseok
Background Total knee arthroplasty (TKA) generates severe postoperative pain in 60% of patients and moderate pain in 30% of patients. Because inadequate postoperative pain control can hinder early physiotherapy and rehabilitation, it is the most influential factor dictating a good outcome. The purpose of this study was to evaluate the effectiveness of continuous psoas compartment block (PCB) in comparison to intravenous patient-controlled analgesia (IVPCA) in TKA patients. Methods 40 TKA patients were randomly divided into 2 groups. Group IVPCA (n = 20) received intravenous patient controlled analgesia (IVPCA) for 48 hours. Group PCB (n = 20) received continuous PCB for 48 hours at the fourth intertransverse process of the lumbar using the C-arm. Pain scores, side effects, satisfaction, the length of hospital stay, rescue antiemetics, and analgesics were recorded. Results Pain scores (VNRS 0-100) were higher in Group IVPCA than in Group PCB. Nausea and sedation occurred more frequently in Group IVPCA than in Group PCB. There were no differences between the groups in the length of the hospital stay, satisfaction scores, and the use of rescue antiemetics and analgesics. Conclusions Continuous PCB seemed to be an appropriate and reliable technique for TKA patients, because it provided better analgesia and fewer side effects such as nausea and sedation when compared to IVPCA. PMID:22323954
Ayoglu, Hilal; Altunkaya, Hanife; Bayar, Ahmet; Turan, Isil Ozkocak; Ozer, Yetkin; Ege, Ahmet
The purpose of this prospective randomized study was to evaluate the effects of intraarticular combinations of tramadol and ropivacaine with ketamine in postoperative pain control of patients undergoing arthroscopic meniscectomy. We randomly divided 80 patients into four groups to receive intraarticular 50 mg tramadol (Group T), 50 mg tramadol with 0.5 mg kg(-1) ketamine (Group TK), 75 mg ropivacaine (Group R), 75 mg ropivacaine with 0.5 mg kg(-1) ketamine (Group RK) in 20 ml normal saline at the end of surgery. Postoperative analgesia was provided with patient-controlled analgesia with morphine. Postoperative pain scores, total morphine consumption amount and side effects were recorded at intervals of 0, 1, 2, 4, 8, 12 and 24 h after the operation. Pain scores were higher in Group T when compared with Group R and Group RK at second and fourth hours, also compared with Group RK at zeroth, first, second, fourth and eighth hours. Total morphine consumption amount was found to be higher in Group T when compared to Group TK at eighth and twelfth hours and Group RK at eighth hours (P < 0.05). Total morphine consumption was lowest in Group TK (P < 0.05). There were no significant differences among the study groups regarding side effects. Administration of intraarticular tramadol-ketamine combination was found to be more effective in decreasing postoperative daily analgesic consumption.
Kim, Do Yun; Chae, Joo Wung; Lim, Chang Hun; Heo, Bong Ha; Park, Keun Suk; Lee, Hyung Gon; Choi, Jeong Il; Yoon, Myung Ha
Background Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. Methods The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. Results When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. Conclusions Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level. PMID:27413481
Fuentealba Cargill, Francisca; Biagini Alarcón, Leandro
There is evidence that acupuncture may relieve pain. To assess the evidence about the effectiveness of acupuncture to relieve postoperative pain. A systematic review of the literature selecting controlled clinical trials and systematic reviews comparing acupuncture with standard pain management. The value and quality of reports were evaluated using Jadad scale and STRICTA protocol. Pain intensity and analgesic consumption were the primary endpoints sought. Five controlled trials and two systematic reviews were selected. A meta-analysis was not feasible due to the heterogeneity of studies. In the postoperative period of tonsillectomy, acupuncture reduced pain by 36 and 22% at 20 minutes and two hours, respectively. In knee replacement, acupuncture reduced pain by 2% and analgesic consumption by 42%. In the postoperative period of dental interventions, acupuncture reduced pain by 24% at two hours. Acupuncture may be useful to manage postoperative pain, but more controlled studies are required.
Pascual, David; Goicoechea, Carlos; Burgos, Elisa; Martín, María Isabel
Nowadays, there are no validated drugs to control the neuropathic pain induced by paclitaxel, one of the most effective antineoplastic drugs. The aim was to study the involvement of opioid and NMDA receptor on established paclitaxel-induced pain, testing three common analgesics drugs morphine, ketamine and methadone. Animals received four intraperitoneal (i.p.) injections on alternate days of paclitaxel (1mg/kg). Three weeks later, animals showed a mechanical and heat allodynia/hyperalgesia. Morphine (1, 2.5, 5 and 10mg/kg) abolished the reduction in the mechanical and thermal withdrawal thresholds in a dose dependent manner. This effect was blocked by naloxone. Only highest dose of ketamine (50mg/kg) was able to increase the mechanical and thermal threshold and returned to basal values. Subanalgesic doses of morphine (1mg/kg) and ketamine (12.5mg/kg) produced an additive effect on heat hyperalgesia reaching an antinociceptive effect. This combination did not induce any change on tactile allodynia. Methadone (2.5 and 5mg/kg) produced an analgesic effect that was completely antagonized by naloxone in both tests. Our results confirm that: the activation of opioids receptor produced analgesia; the blockade of NMDA receptors produce antinociception but at high doses with motor impairments and low doses of ketamine enhancing the effect of opioids.
Gruen, M E; Dorman, D C; Lascelles, B D X
A literature review identified six placebo-controlled studies of analgesics in client-owned cats with degenerative joint disease-associated pain. Five studies with 96 cats had available data. Caregiver responses on a clinical metrology instrument, Client-Specific Outcome Measure (CSOM), were compared to measured activity. Cats were categorised as 'successes' or 'failures' based on change in CSOM score and activity counts from baseline. Effect sizes based on CSOM score were calculated; factors that were associated with success/failure were analysed using logistic regression. Effect sizes ranged from 0.97 to 1.93. The caregiver placebo effect was high, with 54-74 per cent of placebo-treated cats classified as CSOM successes compared with 10-63 per cent of cats classified as successes based on objectively measured activity. 36 per cent of CSOM successes were also activity successes, while 19 per cent of CSOM failures were activity successes. No significant effects of cat age, weight, baseline activity, radiographic score, orthopaedic pain score or study type on CSOM success in the placebo groups were found. The caregiver placebo effect across these clinical trials was remarkably high, making demonstration of efficacy for an analgesic above a placebo difficult. Further work is needed to determine whether a potential placebo-by-proxy effect could benefit cats in clinical settings.
Durmus, N; Bagcivan, I; Ozdemir, E; Altun, A; Gursoy, S
It is aimed to investigate the effects of guanylyl cyclase activation and inhibition on acute morphine antinociception and the development of tolerance to its effect. Nitric oxide-soluble guanylyl cyclase signal transduction cascade suggested to play an important role in the development of tolerance to antinociceptive effects of morphine. Nociception was evaluated by tail flick and hot plate tests in male Wistar rats. The analgesic effects of intraperitoneal protoporphyrin IX (PPIX; an activator of soluble guanylyl cyclase), 3-morpholinosydnonimine hydrochloride (SIN-1; NO donor and activator of guanylyl cyclase), S-Nitroso-N-acetylpenicillamine (SNAP; an activator of guanylyl cyclase), 3,3-Bis (amino ethyl)-1-hydroxy-2-oxo-1-triazene (NOC-18; NO donor activating guanylyl cyclase) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; an inhibitor of guanylyl cyclase) alone or in combination with subcutaneous morphine injection were evaluated. Their effects on morphine tolerance development were evaluated by giving these agents 20 minutes prior to twice daily morphine injection during tolerance development for 5 days. On day 6, the expression of morphine tolerance was determined. PPIX, SIN-1, SNAP and NOC-18 significantly increased expression of morphine tolerance while ODQ decreased. These data suggested that sGC activators have a significant role in tolerance to the analgesic effect of morphine (Tab. 1, Fig. 4, Ref. 29).
Baudesson de Chanville, Audrey; Brevaut-Malaty, Véronique; Garbi, Aurélie; Tosello, Barthelemy; Baumstarck, Karine; Gire, Catherine
Two studies have demonstrated an analgesic effect of maternal milk odor in preterm neonates, without specifying the method of olfactory stimulation. Research aim: This study aimed to assess the analgesic effect of maternal milk odor in preterm neonates by using a standardized method of olfactory stimulation. This trial was prospective, randomized, controlled, double blinded, and centrally administered. The inclusion criteria for breastfed infants included being born between 30 and 36 weeks + 6 days gestational age and being less than 10 days postnatal age. There were two groups: (a) A maternal milk odor group underwent a venipuncture with a diffuser emitting their own mother's milk odor and (2) a control group underwent a venipuncture with an odorless diffuser. The primary outcome was the Premature Infant Pain Profile (PIPP) score, with secondary outcomes being the French scale of neonatal pain-Douleur Aiguë du Nouveau-né (DAN) scale-and crying duration. All neonates were given a dummy. Our study included 16 neonates in the maternal milk odor group and 17 in the control group. Neonates exposed to their own mother's milk odor had a significantly lower median PIPP score during venipuncture compared with the control group (6.3 [interquartile range (IQR) = 5-10] versus 12.0 [IQR = 7-13], p = .03). There was no significant difference between the DAN scores in the two groups ( p = .06). Maternal milk odor significantly reduced crying duration after venipuncture (0 [IQR = 0-0] versus 0 [IQR = 0-18], p = .04). Maternal milk odor has an analgesic effect on preterm neonates.
Bae, Sea-Hyun; Kim, Gi-Do; Kim, Kyung-Yoon
Pain that occurs after a stroke lowers the quality of life. Such post-stroke pain is caused in part by the brain lesion itself, called central post-stroke pain. We investigated the analgesic effects of transcranial direct current stimulation (tDCS) in stroke patients through quantitative sensory testing. Fourteen participants with central post-stroke pain (7 female and 7 male subjects) were recruited and were allocated to either tDCS (n = 7) or sham-tDCS (n = 7) group. Their ages ranged from 45 to 55 years. tDCS was administered for 20 min at a 2-mA current intensity, with anodal stimulations were performed at primary motor cortex. The sham-tDCS group was stimulated 30-second current carrying time. Both group interventions were given for 3 days per week, for a period of 3 weeks. Subjective pain was measured using the visual analogue scale (VAS) of 0 to 10. Sensations of cold and warmth, and pain from cold and heat were quantified to examine analgesic effects. The sham-tDCS group showed no statistically significant differences in time. In contrast, tDCS group showed decreased VAS scores and skin temperature (p < 0.05). The threshold temperatures for the sense of cold and pain from cold increased (p < 0.05), and those for the sense of warmth and pain from heat decreased (p < 0.05). Our findings indicate that tDCS improved sensory identification and exerted analgesic effects in the stroke patients with central post-stroke pain.
Malver, Lasse Paludan; Brokjaer, Anne; Staahl, Camilla; Graversen, Carina; Andresen, Trine; Drewes, Asbjørn Mohr
To assess centrally mediated analgesic mechanisms in clinical trials with pain patients, objective standardized methods such as electroencephalography (EEG) has many advantages. The aim of this review is to provide the reader with an overview of present findings in analgesics assessed with spontaneous EEG and evoked brain potentials (EPs) in humans. Furthermore, EEG methodologies will be discussed with respect to translation from animals to humans and future perspectives in predicting analgesic efficacy. We searched PubMed with MeSH terms 'analgesics', 'electroencephalography' and 'evoked potentials' for relevant articles. Combined with a search in their reference lists 15 articles on spontaneous EEG and 55 papers on EPs were identified. Overall, opioids produced increased activity in the delta band in the spontaneous EEG, but increases in higher frequency bands were also seen. The EP amplitudes decreased in the majority of studies. Anticonvulsants used as analgesics showed inconsistent results. The N-methyl-D-aspartate receptor antagonist ketamine showed an increase in the theta band in spontaneous EEG and decreases in EP amplitudes. Tricyclic antidepressants increased the activity in the delta, theta and beta bands in the spontaneous EEG while EPs were inconsistently affected. Weak analgesics were mainly investigated with EPs and a decrease in amplitudes was generally observed. This review reveals that both spontaneous EEG and EPs are widely used as biomarkers for analgesic drug effects. Methodological differences are common and a more uniform approach will further enhance the value of such biomarkers for drug development and prediction of treatment response in individual patients.
Zhuravleva, M V; Shikh, E V; Makhova, A A
Combined vitamin preparations containing thiamine (vitamin B1), pyridoxine (vitamin B6), and cyanocobalamin (vitamin B12) are widely used in medical practice. The results of investigations have confirmed that it is expedient to potentiate an analgesic effect due to the concurrent use of vitamin B group and nonsteroidal anti-inflammatory drugs given to relieve significant neuropathic pain. Milgamma compositum (Wörwag Pharma, Germany) is one of the most studied drugs on the Russian market, which contains a combination of vitamin B group (including benfotiamin).
Yamamoto, Tatsuo; Miyazaki, Rika; Yamada, Toshihiko
GPR103 is one of the orphan G protein-coupled receptors. Recently, an endogenous ligand for GPR103, 26RFa, was identified. Many 26RFa binding sites have been observed in various nuclei of the brain involved in the processing of pain such as the parafascicular thalamic nucleus, the locus coeruleus, the dorsal raphe nucleus, and the parabrachial nucleus. In the present study, the effects of intracerebroventricular injection of 26RFa were tested in the rat. Intracerebroventricular injection of 26RFa significantly decreased the number of both phase 1 and phase 2 agitation behaviors induced by paw formalin injection. This analgesic effect of 26RFa on the phase 1 response, but not phase 2 response, was antagonized by BIBP3226, a mixed antagonist of neuropeptide Y Y1 and neuropeptide FF receptors. Intracerebroventricular injection of 26RFa has no effect in the 52.5 degrees C hot plate test. Intracerebroventricular injection of 26RFa had no effect on the expression of Fos-like immunoreactivity induced by paw formalin injection in the superficial layers of the spinal dorsal horn. These data suggest that (1) 26RFa modulates nociceptive transmission at the supraspinal site during a formalin test, (2) the mechanism 26RFa uses to produce an analgesic effect on the phase 1 response is different from that on the phase 2 response, and (3) intracerebroventricularly injected 26RFa dose not directly inhibit the nociceptive input to the spinal cord.
Dashti-Rahmatabadi, Mohammad Hossein; Hejazian, Seyed Hassan; Morshedi, Abbas; Rafati, Ali
Pain is a universal complaint, which needs further investigations for new pain relieving agents. Carum copticum (L.) Sprague ex Turrill is a plant in Umbelliferae family, which is mentioned to have some therapeutic effects on headache and joint pains in Iranian traditional literature, but there are not enough scientific reports to prove its effects on pain. So, we conducted to design an experimental clinical trial study to assess and compare the analgesic effect of ethanolic extract of Carum copticum fruit with morphine by using a tail-flick analgesiometer device. Our results indicate that the test drug produced significant increase in tail-flick latency (TFL) during 2h post-drug administration (p<0.05). The peak of the effect was observed at 45min after drug injection, which was comparable to that of 1mg/kg morphine (i.p.). Positive results in this type of analgesiometric test indicate that the antinociceptive action may be of the opoid type. The present study supports the claims of Iranian traditional medicine showing that Carum copticum extract possesses a clear-cut analgesic effect. However, further investigations are required to evaluate the efficacy and safety of this herbal medication in man.
Montana, Michael C.; Conrardy, Beth A.; Cavallone, Laura F.; Kolber, Benedict J.; Rao, Leslie K.; Greco, Suellen C.; Gereau, Robert W.
Background The metabotropic glutamate receptor 5 noncompetitive antagonist fenobam is analgesic in rodents. Future development of fenobam as an analgesic in humans will require a favorable long-term treatment profile and a lack of significant deleterious side effects. This study aimed to determine if tolerance to fenobam’s analgesic effects developed over 14 days and to assess for side effects in mice. Methods Mouse models of pain, locomotor behavior, and coordination were used. Fenobam or vehicle (n = 8 or 11 per group) was administered for 14 days and analgesic tolerance to fenobam was assessed using the formalin test. Histopathology examination and serum chemistry analysis post-14-day fenobam administration were also assessed (n = 12 or 9). The effects of fenobam on locomotor activity were assessed in the open field and elevated zero maze (n = 8 or 7). Coordination was assessed using ledge crossing and vertical pole descent tasks (n = 11 or 10). Results Tolerance to fenobam’s analgesic effect did not develop after 14 days. Chronic fenobam administration resulted in statistically significantly less weight gain compared to vehicle controls, but did not cause any physiologically or statistically significant hematological abnormalities, altered organ function, or abnormal histopathology of the liver, brain, or testes. Fenobam administration resulted in a metabotropic glutamate receptor 5-dependent increase in exploratory behavior but does not impair motor coordination at analgesic doses. Conclusions Analgesic tolerance to repeat fenobam dosing does not develop. Chronic dosing of up to 14-days is well tolerated. Fenobam represents a promising candidate for the treatment of human pain conditions. PMID:22037639
Xia, Jingsheng; Tian, Yuzhen; Barrett, James E.; Dai, Yue; Hu, Huijuan
Chronic pain often accompanies immune responses and immune cells are known to be involved in chronic pain. Store-operated calcium (SOC) channels are calcium-selective cation channels and play an important role in the immune system. YM-58483, a potent SOC channel inhibitor, has been shown to inhibit cytokine production from immune cells and attenuate antigen-induced hypersensitivity reactions. Here, we report that YM-58483 has analgesic actions in chronic pain and produces antinociceptive effects in acute pain and prevents the development of chronic pain in mice. Oral administration of 10 mg/kg or 30 mg/kg YM-58483 dramatically attenuated Complete Freund's adjuvant (CFA)-induced thermal hyperalgesia and prevented the development of thermal and mechanical hypersensitivity in a dose-dependent manner. Analgesic effects were observed when YM-58483 administered systemically, intrathecally, and also intraplantarly. YM-58483 decreased spared nerve injury (SNI)-induced thermal and mechanical hypersensitivity and prevented the development of SNI-induced pain hypersensitivity. Pretreatment with YM-58483 strongly reduced both the first and second phases of formalin-induced spontaneous nocifensive behavior dose-dependently. YM-58483 produced antinociception in acute pain induced by heat or chemical or mechanical stimuli at the dose of 30 mg/kg. YM-58483 diminished CFA-induced paw edema, and reduced production of TNF-α, IL-1β and PGE2 in the CFA-injected paw. In vitro, SOC entry in nociceptors was more robust than in nonnociceptors, and the inhibition of SOC entry by YM-58483 in nociceptors was much greater than in non-nociceptors. Our findings indicate that YM-58483 is a potent analgesic and suggest that SOC channel inhibitors may represent a novel class of therapeutics for pain. PMID:23778292
Fennessy, M. R.; Heimans, R. L. H.; Rand, M. J.
1. Morphine-like analgesic drugs caused depression of twitches of the isolated guinea-pig ileum in response to transmural electrical stimulation. The drugs tested were the narcotic analgesics codeine, diamorphine, fentanyl, morphine, morphine-N-oxide, normorphine, oxymorphone, pethidine, phenazocine and phenoperidine and the analgesic narcotic antagonists nalorphine and pentazocine. 2. With the first application of one of these drugs the extent of depression of twitches was proportional to concentration. Except in the case of pethidine, there was no further depression when additional drug was added to the organ bath. With the second application of a drug after washing out the first dose, the depressant effect was less; that is, tolerance developed. With pethidine, the depression of twitches was proportional to concentration and tolerance could not be observed. 3. When tolerance had been produced by cumulative addition of these drugs, a concentration was reached at which further addition resulted in increased activity of the ileum. 4. With codeine, morphine and normorphine, the twitches were increased in height and regular. 5. With diamorphine, fentanyl, oxymorphone, pentazocine, phenazocine and phenoperidine there were increased but irregular responses to transmural stimulation. 6. Having reached the concentration at which these effects were observed, washout of the drug resulted in reduction of activity; the twitches became smaller or the irregular responses ceased. 7. Readministration of a drug after activity of the ileum had been depressed by withdrawal of that drug resulted in restoration of activity, the ileum being dependent on the presence of the drug for its activity. 8. Codeine and nalorphine did not produce as great an increase in activity on readministration to a dependent ileum as did morphine: they seem to act as partial agonists in producing this effect. 9. In similar experiments with the isolated urinary bladder of the rat and guinea-pig, morphine
de Souza, Maiara Ferreira; Kraychete, Durval Campos
Pain is a public health problem, greatly impairing quality of life. Almost 80% of patients with chronic pain reported that their pain interferes with activities of daily living, and two thirds reported that the pain causes negative impact on their personal relationships. The physical and functional disability, whether temporary or permanent, compromises the professional activity and causes work absenteeism, increasing costs of health systems. The aim of this review is to analyze, based on the literature, the analgesic effect of lidocaine administered intravenously for the treatment of chronic pain and to evaluate the reduction of pain intensity in patients with chronic pain, focusing on musculoskeletal and neuropathic etiology. The method used was a review of the literature, consisting in searching the scientific literature on the efficacy of intravenous lidocaine infusion in the treatment of patients with chronic pain. Of the 19 studies reviewed, 12 had results that confirm the analgesic effect of intravenous lidocaine in patients with chronic pain. Most authors used doses of 5mg/kg infused for 30minutes or more, producing significant analgesia with variable duration (minutes to weeks). Based on the literature review, it is not possible to uniformly specify the most effective and safe dose of lidocaine administered intravenously for the treatment of neuropathic or musculoskeletal pain. As for effectiveness, the intravenous infusion of lidocaine as an alternative for the treatment of chronic pain of various etiologies seems very promising, but further studies need to be conducted. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.
Todorovic, Slobodan M; Rastogi, A J; Jevtovic-Todorovic, Vesna
Anticonvulsant agents are commonly used to treat neuropathic pain conditions because of their effects on voltage- and ligand-gated channels in central pain pathways. However, their interaction with ion channels in peripheral pain pathways is poorly understood. Therefore, we studied the potential analgesic effects of commonly used anticonvulsant agents in peripheral nociception. We injected anticonvulsants intradermally into peripheral receptive fields of sensory neurons in the hindpaws of adult rats, and studied pain perception using the model of acute thermal nociception. Commonly used anticonvulsants such as voltage-gated Na+ channel blockers, phenytoin and carbamazepine, and voltage-gated Ca2+ channel blockers, gabapentin and ethosuximide, induced dose-dependent analgesia in the injected paw, with ED50 values of 0.30, 0.32 and 8, 410 μg per 100 μl, respectively. Thermal nociceptive responses were not affected in the contralateral, noninjected paws, indicating a lack of systemic effects with doses of anticonvulsants that elicited local analgesia. Hill slope coefficients for the tested anticonvulsants indicate that the dose–response curve was less steep for gabapentin than for phenytoin, carbamazepine and ethosuximide. Our data strongly suggest that cellular targets like voltage-gated Na+ and Ca2+ channels, similar to those that mediate the effects of anticonvulsant agents in the CNS, may exist in the peripheral nerve endings of rat sensory neurons. Thus, peripherally applied anticonvulsants that block voltage-gated Na+ and Ca2+ channels may be useful analgesics. PMID:12970103
Chao, Jung; Liao, Jiunn-Wang; Peng, Wen-Huang; Lee, Meng-Shiou; Pao, Li-Heng; Cheng, Hao-Yuan
The aim of this study was to evaluate pharmacological properties of ethanol extracted from Mahonia oiwakensis Hayata stems (MOSEtOH). The pharmacological properties included antioxidant, analgesic, anti-inflammatory and hepatoprotective effects. The protoberberine alkaloid content of the MOSEtOH was analyzed by high-performance liquid chromatography (HPLC). The results revealed that three alkaloids, berberine, palmatine and jatrorrhizine, could be identified. Moreover, the MOSEtOH exhibited antioxidative activity using the DPPH assay (IC50, 0.743 mg/mL). The DPPH radical scavenging activity of MOSEtOH was five times higher that that of vitamin C. MOSEtOH was also found to inhibit pain induced by acetic acid, formalin, and carrageenan inflammation. Treatment with MOSEtOH (100 and 500 mg/kg) or silymarin (200 mg/kg) decreased the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the CCl4-treated group. Histological evaluation showed that MOSEtOH reduced the degree of liver injury, including vacuolization, inflammation and necrosis of hepatocytes. The anti-inflammatory and hepatoprotective effect of MOSEtOH were found to be related to the modulation of antioxidant enzyme activity in the liver and decreases in malondialdehyde (MDA) level and nitric oxide (NO) contents. Our findings suggest that MOSEtOH has analgesic, anti-inflammatory and hepatoprotective effects. These effects support the use of MOSEtOH for relieving pain and inflammation in folk medicine. PMID:23364614
Kim, H.; Ku, S.-Y.; Kim, H. C.; Suh, C. S.; Kim, S. H.; Choi, Y. M.
Introduction: Several studies have found anesthetic agents including propofol in ovarian follicular fluid. However, little is known about the effect of anesthetic agents on ovarian function. We aimed to investigate whether there were differences in the postoperative levels of sex hormones when propofol was used as the anesthetic agent. Methods: A retrospective review was done of 80 patients who underwent ovarian surgery, with 72 infertile women serving as controls. Patients were included in the study if their serum estradiol (E2) and follicle stimulating hormone (FSH) levels were measured during their first postoperative menstrual cycle. Results: Patients were grouped according to the use or non-use of propofol as follows: propofol group (n = 39) and non-propofol group (n = 41). The control group did not undergo surgery. Postoperative E2 levels did not differ between the three groups, but FSH levels were significantly higher in the patients who had undergone surgery compared to controls (p < 0.05). Post-hoc analysis of E2 and FSH levels in the propofol and non-propofol groups did not show any significant differences. Conclusions: The use of propofol did not result in any differences compared to other anesthetic agents in terms of postoperative sex hormone levels after gynecologic surgery. The type of anesthetic agent does not seem to affect the postoperative levels of female sex hormones. PMID:27134297
Ashjian, Peter; Chen, Constance M; Pusic, Andrea; Disa, Joseph J; Cordeiro, Peter G; Mehrara, Babak J
Numerous protocols exist to prevent thrombosis after free-tissue transfer. Many surgeons advocate using aspirin or other antiplatelet agents, but little objective evidence supports this practice. This study evaluates the rate of microvascular thrombosis in patients undergoing free-tissue transfer treated with or without antiplatelet agents. All consecutive free flaps from 2002-2005 at a single center were reviewed using a prospectively maintained database. Patients were in 2 groups based on postoperative anticoagulation administration. In group 1, 325 mg of aspirin was administered daily for 5 days postoperatively. In group 2, patients were treated with 5000 units of low-molecular-weight heparin (LMWH) per day until ambulating. Patient demographics, procedure type, diagnosis, adjuvant treatment, and procedure type were recorded. Outcome variables included microvascular thrombosis, partial or total flap loss, hematoma, bleeding, deep venous thrombosis (DVT), pulmonary embolism, and death. Four hundred seventy patients underwent 505 microvascular free flaps to reconstruct oncologic defects. Two hundred sixty flaps (group A) received postoperative aspirin therapy; 245 flaps (group B) received LMWH therapy. Both groups were statistically similar in their composition. No statistically significant difference was noted between the 2 groups when comparing outcome variables including microvascular thrombosis, partial or total flap loss, hematoma, bleeding, DVT, pulmonary embolism, and death. Postoperative anticoagulation choice has no statistically significant effect on the incidence of free flap complications, including bleeding, thromboembolism, and flap loss. We conclude that aspirin or LMWH therapy demonstrates equivalent outcomes when used as single-agent postoperative anticoagulation in oncologic free flap reconstruction.
Frye, Reginald F.; Stavropoulos, Mary F.; Herman, Mary A.; Hastie, Barbara A.
Background Caffeine reduces the amount of analgesic medications necessary to provide postoperative pain (POP) relief and augments treatments for headaches and dental pain. Despite considerable evidence of its beneficial effects, little is understood about the role of dietary caffeine consumption on baseline pain sensitivity or POP following oral surgery. Method Baseline experimental pain testing (quantitative sensory testing [QST]) using four stimulus modalities was conducted on 30 healthy adults (53% females) before surgical extraction of four third molars. Self-reported caffeine ingestion was reported before QST, and on the day of surgery, preoperative and postoperative caffeine plasma concentrations (CPC) were measured by mass spectrometry. POP ratings were obtained at timed intervals. Results In QST, compared to subjects who self-reported no caffeine intake, those who self-reported caffeine ingestion demonstrated a higher pain sensitivity, particularly, on ramp and hold sustained heat at 44°C and 46°C, as well as a lower heat pain threshold and tolerance (p=0.05). Differences approached significance (p=0.06) in POP between subjects with CPC above 300 ng/mL and those with CPC below 300 ng/mL. Specifically, those with >300 ng/mL CPC had a slightly lower POP (mean 2.43, range 0–5) compared to those with <300 ng/mL CPC whose POP ratings were slightly higher (mean 2.89) with a greater variability (range 0–9.5). Conclusions Self-reported, dietary caffeine intake was associated with higher QST ratings with lower threshold and tolerance particularly on heat pain modalities. External factors (i.e., analgesic dosage) may have played a role in the analgesic effects of caffeine on POP in oral surgery, especially in individuals with CPC exceeding 300 ng/mL who reported lower pain. PMID:24761271
Karunathilake, Nirmani P; Frye, Reginald F; Stavropoulos, Mary F; Herman, Mary A; Hastie, Barbara A
Caffeine reduces the amount of analgesic medications necessary to provide postoperative pain (POP) relief and augments treatments for headaches and dental pain. Despite considerable evidence of its beneficial effects, little is understood about the role of dietary caffeine consumption on baseline pain sensitivity or POP following oral surgery. Baseline experimental pain testing (quantitative sensory testing [QST]) using four stimulus modalities was conducted on 30 healthy adults (53% females) before surgical extraction of four third molars. Self-reported caffeine ingestion was reported before QST, and on the day of surgery, preoperative and postoperative caffeine plasma concentrations (CPC) were measured by mass spectrometry. POP ratings were obtained at timed intervals. In QST, compared to subjects who self-reported no caffeine intake, those who self-reported caffeine ingestion demonstrated a higher pain sensitivity, particularly, on ramp and hold sustained heat at 44°C and 46°C, as well as a lower heat pain threshold and tolerance (p=0.05). Differences approached significance (p=0.06) in POP between subjects with CPC above 300 ng/mL and those with CPC below 300 ng/mL. Specifically, those with >300 ng/mL CPC had a slightly lower POP (mean 2.43, range 0-5) compared to those with <300 ng/mL CPC whose POP ratings were slightly higher (mean 2.89) with a greater variability (range 0-9.5). Self-reported, dietary caffeine intake was associated with higher QST ratings with lower threshold and tolerance particularly on heat pain modalities. External factors (i.e., analgesic dosage) may have played a role in the analgesic effects of caffeine on POP in oral surgery, especially in individuals with CPC exceeding 300 ng/mL who reported lower pain.
Ballantyne, Jane C
Opioid analgesics have been used increasingly over the past 20 years for the management of chronic non-cancer pain in the USA under the assumption that they were safe and effective when used as directed. The accuracy of that assumption has not been tested against accumulated evidence. The safety of opioids used on a long-term basis has not been tested in clinical trials. Epidemiologic evidence from examinations of such use in the general population indicates that the risk of overdose increases in a dose-response manner. Such evidence also suggests increased risk of fractures and acute myocardial infarctions among elderly users of opioids for chronic pain. Experimental evidence supports short-term use of opioids, but trials of long-term use for chronic pain have not been conducted. Epidemiologic evidence suggests that long-term use does not result in improvement in function or quality of life while being associated with significant dropout rates and a high prevalence of adverse drug effects. Substantial fractions of patients are not using opioid analgesics as directed, while millions of US residents are using them without a prescription for nonmedical reasons. A prudent treatment approach consistent with the available evidence would be to reserve chronic opioid therapy for serious pain-related problems for which the effectiveness of opioids has been demonstrated and for patients whose use as directed is assured through close monitoring and for whom an explicit, informed calculation has been made that the benefits of opioids outweigh the risks.
Faria, Juliana; Barbosa, Joana; Leal, Sandra; Afonso, Luís Pedro; Lobo, João; Moreira, Roxana; Queirós, Odília; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge
Tramadol and tapentadol are extensively prescribed for the treatment of moderate to severe pain. Although these drugs are very effective in pain treatment, the number of intoxications and deaths due to both opioids is increasing, and the underlying toxic mechanisms are not fully understood. The present work aimed to study the potential biochemical and histopathological alterations induced by acute effective (analgesic) doses of tramadol and tapentadol, in Wistar rats. Forty-two male Wistar rats were divided into different groups: a control, administered with normal saline solution, and tramadol- or tapentadol-treated groups (10, 25 or 50mg/kg - typical effective analgesic dose, intermediate and maximum recommended doses, respectively). 24h after intraperitoneal administration, biochemical and oxidative stress analyses were performed in blood, and specimens from brain, lung and heart were taken for histopathological and oxidative stress studies. Both drugs caused an increase in the AST/ALT ratio, in LDH, CK and CK-MB activities in serum samples, and an increase in lactate levels in serum and brain samples. Oxidative damage, namely protein oxidation, was found in heart and lung tissues. In histological analyses, tramadol and tapentadol were found to cause alterations in cell morphology, inflammatory cell infiltrates and cell death in all tissues under study, although tapentadol caused more damage than tramadol. Our results confirmed the risks of tramadol exposure, and demonstrated the higher risk of tapentadol, especially at high doses. Copyright © 2017 Elsevier B.V. All rights reserved.
Lim, Dong Wook; Kim, Jae Goo; Lim, Eun Yeong; Kim, Yun Tai
The root of Withania somnifera, commonly known as ashwagandha, is a traditional herb in the Indian Ayurvedic system of medicine and is used as a tonic. Here, we investigated whether W. somnifera root extract exhibits analgesic effects in plantar incision (PI) and spared nerve injury (SNI) rat models. Mechanical withdrawal threshold (MWT) was measured by von Frey filaments, and pain-related behavior was determined after operation by ultrasonic vocalization (USV) measurements. Indeed, we examined interferon-γ (IFN-γ) and interleukin-10 (IL-10) levels in the isolated dorsal root ganglia (DRG) following SNI in rats using an ELISA cytokine assay. MWT significantly increased 6 and 24 h after PI in rats receiving W. somnifera root extracts (100 and 300 mg/kg). Furthermore, the number of 22-27-kHz USV, which are a distress response, was significantly reduced at 6 and 24 h after PI in W. somnifera-treated rats (100 and 300 mg/kg). SNI-induced hyperalgesia and cytokine levels were significantly alleviated after treating with W. somnifera root extracts (100 and 300 mg/kg) for 15 continuous days. The main active compound, withaferin A, from the W. somnifera root extract has shown the CC chemokine family Receptor 2 (CCR2) antagonistic effects on monocyte chemoattractant protein-1 (MCP-1)-induced Ca(2+) response in CCR2 stable cell line. These results indicate that W. somnifera root extract has a potential analgesic effect in rat models for both postoperative and neuropathic pain and shows potential as a drug or supplement for the treatment of pain.
Iwagaki, Hiromi; Saito, Shinya
We studied the effects of preoperative administration of Hochuekkito (TJ-41) on the host response of patients undergoing gastrectomy or colectomy in a prospective, randomized, multicenter clinical trial. Forty-eight patients were randomized into two groups: one received 7.5 g/day of TJ-41 for 7 days before surgery (n = 22); and the other served as the control group (n = 26). The body temperature and pulse rate in patients in the TJ41 group were significantly better controlled during the study compared with those in the control group. The concentration of serum cortisol on the first postoperative day in the TJ-41 group was also significantly lower compared with that in the control group. These results clearly indicate that the preoperative administration of TJ-41 may ameliorate an excessive postoperative inflammatory response and prolonged immunosuppressed state, resulting in fewer postoperative infectious complications.
HyrkÃ¤s, T.; Ylipaavalniemi, P.; Oikarinen, V. J.; Paakkari, I.
The efficacies of bupivacaine and lidocaine together with a preoperatively administered single-dose oral combination of normal- and sustained-release preparations of diclofenac in preventing postoperative pain after third molar removal were compared in a double-blind crossover study. Bilaterally impacted lower third molars were removed in two sessions. Each patient was given one type of local anesthetic on one session and the other in the second. Pain was recorded using a visual analog scale. When the diclofenac combination (150 mg) was given before the operation, postoperative analgesia was better with bupivacaine plus diclofenac than with lidocaine plus diclofenac. Twenty-five out of 40 patients preferred bupivacaine to lidocaine for local anesthesia. It is possible to achieve effective postoperative pain prevention by combining bupivacaine and preoperative normal- and sustained-release preparations of diclofenac. PMID:8629744
Saritas, Z K; Saritas, T B; Pamuk, K; Korkmaz, M; Yaprakci, M V; Yilmaz, O; Demirkan, I
To investigate the postoperative analgesic effects of preemptive dexketoprofen trometamol in dogs subjected to ovariohysterectomy (OHE). Seventeen adult bitches of various breeds were used in this study. The dogs were randomly allocated into of two groups. Subjects in the dexketoprofen trometamol (DEX) group (n=10), received intravenous (i.v.) dexketoprofen trometamol, 1 mg/kg, 15 minutes before premedication, while those assigned to the control (C) group (n=7) were given no analgesics prior to premedication. Pain level was assessed by two researchers before the administration of anaesthesia (15 minutes before start) and 0, 1, 2, 4 and 6 hours after surgery. A modified University of Melbourne Pain Scale (UMPS) was used to evaluate pain in both groups. Serum cortisol level changed from 0 to 1 h and from 0 to 1 to 4 h were compared between the groups; the increase in the C group was statistically significant. The modified UMPS was applied to both groups at baseline and postoperative 1, 2, 4 and 6 h. According to this test, the values for DEX were significantly lower than controls at 4 and 6 h (p<0.001). Stable vital signs with unchanged biochemical parameters on dexketoprofen administration are a promising finding. The clinical advantage shown by the pain scale difference and the low serum cortisol levels should qualify dexketoprofen for preemptive pain management in dogs (Tab. 5, Fig. 2, Ref. 30).
Aabakke, Anna J M; Holst, Lars B; Jørgensen, Jørgen C; Secher, Niels J
Methylprednisolone has been shown to have analgesic effects after orthopedic surgery. The objective of this trial was to compare the effect of 125 mg methylprednisolone with placebo on postoperative pain after abdominal hysterectomy. In this randomized double-blinded placebo-controlled trial women scheduled for elective abdominal hysterectomy (n=59) were randomized to preoperatively receive either 125 mg methylprednisolone or saline intravenously. Primary outcome was postoperative pain measured on a 0.0-10.0 visual analog scale and assessed at rest and during mobilization repeatedly the first 24h and daily on the 2nd to 7th postoperative day. Secondary outcomes were postoperative use of opioids and antiemetics, vomiting, C-reactive protein levels, and time to mobilization and discharge. Repeated measures including the primary outcome were analyzed with linear mixed models. Forty-nine cases were analyzed (methylprednisolone n=25, placebo n=24). Pain scores were significantly higher in the methylprednisolone group compared to the placebo group during mobilization (0.79 [95% confidence intervals (CI) 0.07-1.50] P=0.03) but not at rest (0.55 [95% CI: -0.06 to 1.16] P=0.08). There was no difference between the methylprednisolone and placebo group regarding use of opioids (P=0.24) and antiemetics (P=0.14), number of vomits (P=0.26), and time to mobilization (P=0.24) and discharge (P=0.28). C-reactive protein levels were significantly higher in the placebo group (P=0.01). This trial showed no beneficial effect of methylprednisolone on postoperative pain after abdominal hysterectomy. Methylprednisolone significantly lowered postoperative CRP levels. ClinicalTrial.gov: www.clinicaltrials.gov: NCT01106547. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
Olapour, Alireza; Behaeen, Kaveh; Akhondzadeh, Reza; Soltani, Farhad; al Sadat Razavi, Forough; Bekhradi, Reza
Background Pain is a major problem in patients after cesarean and medication such as aromatherapy which is a complementary therapy, in which the essences of the plants oils are used to reduce such undesirable conditions. Objectives In this study, the effect of aromatherapy using Lavender (Lavandula) essential oil on cesarean postoperative pain was assessed. Materials and Methods In a triple blind, randomized placebo-controlled trial study, 60 pregnant women who were admitted to a general hospital for cesarean section, were divided randomly into two groups. After cesarean, the Lavender group inhaled about 3 drops of 10% Lavender oil essence and the placebo group inhaled 3 drops of placebo after the start of postoperative pain, four, eight and 12 hours later, for 5 minutes from the 10 cm distance. Patient's pain was measured by the VAS (Visual Analog Scale) score before and after each intervention, and vital sign, complications and level of satisfaction of every patient were recorded before and after aromatherapy. Results There was no statistically significant difference between groups in age, height, weight, and time to the first analgesic requirement. Patients in the Lavender group had less postoperative pain in four (P = 0.008), eight (P = 0.024) and 12 (P = 0.011) hours after first medication than the placebo group. The decreased heart rate and patients' level of satisfaction with analgesia were significantly higher in the Lavender group (P = 0.001). In the placebo group, the use of diclofenac suppositories for complete analgesia was also significantly higher than the Lavender group (P = 0.008). Conclusions The inhaled Lavender essence may be used as a part of the multidisciplinary treatment of pain after cesarean section, but it is not recommended as the sole pain management. PMID:24223363
Kashefimehr, A; Babaloo, A; Ghanizadeh, M; Ghasemi, S H; Mollazadeh, H
Pain is a subjective feeling and one of the defense and alerting mechanisms of the body, which is distinguished from the body senses, including touch sensation and perception of heat, cold, pressure, etc. Pain, discomfort, and edema are very common after dental procedures, especially after periodontal surgeries, usually occurring during the first 24 hours after surgery; such pains are classified as medium to severe pains. Generally, medications are used to manage patients' pain and discomfort. One of the most commonly used medications for pain control is Ibuprofen, which is one of the NSAIDs and is a simple derivative of phenylpropionic acid. There is evidence that caffeine alone or in association with Acetaminophen, Ibuprofen, or Aspirin can increase their analgesic effects. Novafen is a new drug which consists of Acetaminophens, Ibuprofen and caffeine and has been marketed in Iran in recent years. 70 subjects referring to the Department of Oral and Maxillofacial Surgery, Tabriz Faculty of Dentistry, who were candidates for crown lengthening procedure, were randomly selected and included in the present study, based on inclusion and exclusion criteria. No significant differences were detected in pain severity between the two groups either clinically or statistically at 30-minutes postoperative interval. Pain, discomfort, and edema are very common after dental procedures, especially after periodontal surgeries. Such conditions usually occur during the first 24-hours postoperative interval and are considered moderate to severe pains. Although in the present study, the administration of Novafen before periodontal surgery resulted in the relief of postoperative pain, further studies are recommended on the subject, The administration of Novafen before periodontal surgeries resulted in pain relief after surgery.
Olapour, Alireza; Behaeen, Kaveh; Akhondzadeh, Reza; Soltani, Farhad; Al Sadat Razavi, Forough; Bekhradi, Reza
Pain is a major problem in patients after cesarean and medication such as aromatherapy which is a complementary therapy, in which the essences of the plants oils are used to reduce such undesirable conditions. In this study, the effect of aromatherapy using Lavender (Lavandula) essential oil on cesarean postoperative pain was assessed. In a triple blind, randomized placebo-controlled trial study, 60 pregnant women who were admitted to a general hospital for cesarean section, were divided randomly into two groups. After cesarean, the Lavender group inhaled about 3 drops of 10% Lavender oil essence and the placebo group inhaled 3 drops of placebo after the start of postoperative pain, four, eight and 12 hours later, for 5 minutes from the 10 cm distance. Patient's pain was measured by the VAS (Visual Analog Scale) score before and after each intervention, and vital sign, complications and level of satisfaction of every patient were recorded before and after aromatherapy. There was no statistically significant difference between groups in age, height, weight, and time to the first analgesic requirement. Patients in the Lavender group had less postoperative pain in four (P = 0.008), eight (P = 0.024) and 12 (P = 0.011) hours after first medication than the placebo group. The decreased heart rate and patients' level of satisfaction with analgesia were significantly higher in the Lavender group (P = 0.001). In the placebo group, the use of diclofenac suppositories for complete analgesia was also significantly higher than the Lavender group (P = 0.008). The inhaled Lavender essence may be used as a part of the multidisciplinary treatment of pain after cesarean section, but it is not recommended as the sole pain management.
Al-Suwayeh, Saleh A.; Taha, Ehab I.; Al-Qahtani, Fahad M.; Ahmed, Mahrous O.; Badran, Mohamed M.
The current study was designed to develop a topical gel formulation for improved skin penetration of lornoxicam (LOR) for enhancement of its analgesic activity. Moreover, the effect of different penetration enhancers on LOR was studied. The LOR gel formulations were prepared by using hydroxylpropyl methylcellulose (HPMC) and carbopol. The carbopol gels in presence of propylene glycol (PG) and ethanol were developed. The formulated gels were characterized for pH, viscosity, and LOR release using Franz diffusion cells. Also, in vitro skin permeation of LOR was conducted. The effect of hydroxypropyl β-cyclodextrin (HP β-CD), beta-cyclodextrin (β-CD), Tween 80, and oleic acid on LOR permeation was evaluated. The optimized LOR gel formulation (LORF8) showed the highest flux (14.31 μg/cm2/h) with ER of 18.34 when compared to LORF3. Incorporation of PG and HP β-CD in gel formulation (LORF8) enhanced the permeation of LOR significantly. It was observed that LORF3 and LORF8 show similar analgesic activity compared to marketed LOR injection (Xefo). This work shows that LOR can be formulated into carbopol gel in presence of PG and HP β-CD and may be promising in enhancing permeation. PMID:25045724
Ahmad, Mansoor; Muhammed, Shafi; Mehjabeen; Jahan, Noor; Jan, Syed Umer; Qureshi, Zia-Ul-Rehaman
Current study was carried out on Rhazya stricta. Plant material was collected from Jhalmagsi Dist. Balochistan, Pakistan. Methanolic extract of Rhazya stricta was tested for anti-dermatitis, analgesic, anxiolytic effects, insecticidal activity and Brine shrimp Bioassay. Crude extract showed significant anti-dermatitis activity, as the results of intensity score showed mild Excoriation or erosion, moderate Edema or populations and absence of Erythema or hemorrhage, Scratching time was decreased to 1.45 and histological observations of mice treated with crude extract showed mild changes and few inflammatory cells in several microscopic fields. The results of analgesic activity were significant and the percentage inhibition of writhes were 73.54% and 69.38% at 300mg/kg and 500mg/kg respectively. The overall response of crude extract in anxiolytic activities were depressive and crude extract showed sedative effects. In Brine shrimp (Artemsia salina) lethality bioassay crude extract showed dose depended significant activity, and showed positive lethality with LD(50) 3.3004μg/ml. Insecticidal activity was positive against Callosbruchus analis, the percent mortality was 40%.
Tronino, Diana; Offerta, Alessia; Ostacolo, Carmine; Russo, Roberto; De Caro, Carmen; Calignano, Antonio; Puglia, Carmelo; Blasi, Paolo
N-Palmitoylethanolamide showed great therapeutic potential in the treatment of inflammation and pain but its unfavourable pharmacokinetics properties will hinder its use in the clinical practice. A nanotechnology-based formulation was developed to enhance the probability of N-palmitoylethanolamide therapeutic success, especially in skin disease management. Lipid nanoparticles were produced and characterized to evaluate their mean size, ζ-potential, thermal behaviour, and morphology. The ability of N-palmitoylethanolamide to diffuse across the epidermis as well as anti-inflammatory and analgesic effects were investigated. Particles had a mean size of about 150 nm and a ζ-potential of -40 mV. DSC data confirmed the solid state of the matrix and the embedding of N-palmitoylethanolamide while electron microscopy have evidenced a peculiar internal structure (i.e., low-electrondense spherical objects within the matrix) that can be reliably ascribed to the presence of oil nanocompartments. Lipid nanoparticles increased N-palmitoylethanolamide percutaneous diffusion and prolonged the anti-inflammatory and analgesic effects in vivo. Lipid nanoparticles seem a good nanotechnology-based strategy to bring N-palmitoylethanolamide to clinics.
Postoperative patients differ in their response to pain and opioids. It is therefore important that nurses offer other options as adjuvants to medication. Relaxation and music may reduce pain by interrupting the postoperative cycle of pain, muscle tension and sympathetic activity. This review summarizes and critiques studies on the effectiveness of relaxation and music use during postoperative pain. Relaxation and music were effective in reducing affective and observed pain in the majority of studies, but they were less often effective in reducing sensory pain or opioid intake. However, the between-study differences in surgical procedures, experimental techniques, activities during testing, measurement of pain, and amount of practice make comparisons difficult. Furthermore, within studies, the problems of inadequate sample size, lack of random assignment, no assurance of pretest equivalence, delayed post-test administration and no control for opiates at the time of test