Non-steroidal anti-inflammatory drugs ketorolac and etodolac can augment the treatment against pneumococcal meningitis by targeting penicillin-binding proteins.

BACKGROUND: Streptococcus pneumoniae is the principal etiological agent of acute bacterial meningitis (ABM) which has fatal outcome in children and elderly. Due to poor blood-brain barrier (BBB) permeation, conventional ß-lactam antibiotics fail to establish the requisite bactericidal concentration in central nervous system leading to resistance in meningeal infections. The present study intended to identify potential therapeutic alternatives against Streptococcal meningitis. METHODS: Virtual screening, pharmacokinetics/pharmacodynamics (PK/PD) and anti-bacterial evaluations were employed to screen potential drugs. Molecular docking and structural dynamics simulations were performed to analyze the binding affinity and interaction stability of the drugs against the conventional Penicillin binding protein (PBP) targets. Screened drugs were also checked for interactions with other possible Streptococcal targets and relevant host targets. RESULTS: Non-steroidal anti-inflammatory drugs (NSAIDs) ketorolac and etodolac exhibiting high BBB-permeation and anti-bacterial potency were identified. Ketorolac and etodolac possessed uniform binding affinities against PBP1A, PBP2X, PBP2B and PBP3 with low inhibition constants (<50 µM). Against PBP2B and PBP3, higher binding affinities were observed for ketorolac (-6.45 and -6Kcal/mol respectively) and etodolac (-6.36 and -6.55Kcal/mol respectively) than penicillin (-5.95 and -5.85Kcal/mol respectively) and cefotaxime (-5.08 and -5.07Kcal/mol respectively). The binding affinities were contributed by conventional H-bonds and non-canonical interactions with active site residues of PBPs. Structural dynamics simulations further indicated the overall stability of the drug-bound complexes through minimal overall average root-mean square fluctuations (RMSFs) (<1.0 Å). The average binding affinities of Ketorolac and Etodolac with PBPs were marginally higher than other Streptococcal targets and comparable to their conventional inflammatory targets. CONCLUSION: Pharmacological and structural profiles indicated that ketorolac and etodolac can potentially subdue the cause and effects of streptococcal meningitis and hence encourage experimental validations.

The Efficacy of Local Anesthesia for Postoperative Pain Control in Breast Augmentation Surgery: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Breast augmentation can cause severe postoperative pain; therefore, some surgeons perform wound infiltration with a local anesthetic solution. This study investigated the postoperative pain relief of local analgesics in breast augmentation surgery. METHODS: We searched three databases for randomized controlled trials evaluating the outcomes of local wound irrigation with local analgesics during or after breast augmentation surgery. The solutions included ropivacaine, bupivacaine, bupivacaine plus ketorolac. The control groups may be saline alone or no irrigation. Network meta-analysis was further employed based on the frequentist approach. Outcomes were reported as weighted mean differences with 95% confidence intervals. RESULTS: Comparisons between the interventions of our included studies revealed that only bupivacaine plus ketorolac (versus placebo) significantly reduced pain at 1 h postoperatively, as indicated by the visual analog scale pain score reduction of 2.22 (- 3.98, - 0.47). Other comparisons showed no significant differences. Moreover, three of the included studies reported postoperative medication use. Two of them reported that postoperative narcotic use was reduced, but the others did not report any such reduction. CONCLUSIONS: Our results showed possibility that local irrigation with bupivacaine plus ketorolac might reduce pain 1 h after surgery. In addition, local anesthesia might reduce postoperative narcotic use. However, due to the small number of included studies, the clinical benefits of local anesthesia in breast augmentation surgery require further confirmation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Effect of Perianal Tramadol Infiltration on Postoperative Pain Following Hemorrhoidectomy.

INTRODUCTION: The present study was attempted to evaluate the effect of perianal infiltration of tramadol on postoperative pain in patients undergoing hemorrhoidectomy. METHOD: This double-blind clinical trial study was carried out on 90 patients with grade 3 and 4 hemorrhoids undergoing hemorrhoidectomy. Patients were randomly assigned into 3 groups of control or bupivacaine or tramadol. Before the surgery, perianal infiltration of .25% bupivacaine or tramadol or normal saline was prescribed to each group, respectively. Data on pain severity (based on the visual analog scale (VAS), the duration of surgery, sedation score, pain at the first defecation, first request time for additional analgesia, nausea and vomiting, and analgesic intakes) were evaluated and analyzed. RESULTS: Duration of surgery was almost similar in all 3 groups (P = .974). The results showed a significant difference in pain score between 3 groups (P ≤.05) at all times after the surgery. In addition, the means of sedation scores (P = .03), pain score at the first defecation (P = .001), the time to first analgesic request (P = .001), and ketorolac administration times (P = .01) were significantly different between 3 groups. Finally, no complication was reported regarding postoperative nausea and vomiting. CONCLUSION: Given the notable efficacy of tramadol in reducing pain after hemorrhoidectomy and its minor side effects, this medication is suggested as an effective topical anesthetic to decrease pain after hemorrhoidectomy.

A randomized comparative evaluation of local infiltration analgesia, extended nerve blocks, and conventional analgesia in pain management after total knee arthroplasty.

OBJECTIVES: The aim of this study was to analyze the postoperative effects of extended nerve blocks and local infiltration analgesia (LIA) on postoperative pain control, muscle weakness, and blood loss after total knee arthroplasty (TKA). PATIENTS AND METHODS: Between February 24th 2020 and July 10th 2020, a total of 161 patients (55 males, 106 females; median age: 69.0 years [IQR 63.0-75.0], range, 41 to 81 years) who underwent primary TKA were randomly allocated into three parallel groups according to their concomitant procedure in a double-blind fashion: (i) those to whom nerve blockade was performed after competition of surgery under the duration of spinal anesthesia (n=50); (ii) those to whom LIA was performed during surgery (n=52), and (iii) control group (n=59). The content of LIA was 10-10 mL of 20 mg lidocaine with 0.01 mg adrenalin and 100 mg ropivacaine, 1 mL (30 mg) ketorolac, and 5 mL (500 mg) tranexamic acid was diluted by 50 mL 0.9% NaCl under aseptic conditions. Outcome parameters were the evaluation of pain until the evening of first postoperative day (24 to 36 h), mobilization, and blood loss within the first three postoperative days. RESULTS: The pain was maximal between 4 and 8 h postoperatively, when the effect of the spinal anesthetic drugs disappeared. During this critical period, tolerable pain (Numerical Rating Scale, NRS ≤3) was observed in 52%, 42%, and 19% of nerve blockade in LIA and control groups, respectively. None of the patients complained of high-intensity pain (NRS >8) in the LIA group, which was a significant difference from the block and control groups (10% and 14%, p<0.008, respectively). There was no significant muscle weakness associated with the use of this extended block. The decrease in hemoglobin level was significantly lower in the LIA group than in the control and block groups (odds ratio [OR]: 0.379, 95% confidence interval [CI]: 0.165-0.874 for nerve blockade vs. LIA, OR: 1.189, 95% CI: 0.491-2.880 for nerve blockade vs. control, OR: 0.319, 95% CI: 0.140-0.727, respectively). The common language effect size for pain in each referred interval in each group and for decrease of hemoglobin between the first and third postoperative days fell between 0.507 and 0.680. CONCLUSION: This study demonstrates that LIA technique offers a fast and safe treatment option for pain relief after TKA. No clinically relevant muscle weakness was observed among groups according to field block applications. Significant advantages were also achieved in blood loss.

The Analgesic Benefits of Ketorolac to Local Anesthetic Wound Infiltration Is Statistically Significant But Clinically Unimportant: A Comprehensive Systematic Review and Meta-Analysis.

Objective: Even though ketorolac-infiltration is said to provide superior postoperative analgesic benefits in different surgical procedures, its safety and efficacy remain to be validated because of the lack of high-quality evidence. We aimed to summarize the efficacy and safety of ketorolac-infiltration based on published randomized-controlled trials (RCTs). Approach: This work followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, assessing the methodological quality of systematic reviews and the Cochrane Collaboration recommendations. We searched for RCTs evaluating the efficacy of ketorolac-infiltration in adults in the PubMed, Web of Science, Embase, Cochrane Library, Chinese databases, and Google Scholar. The two co-primary outcomes of this meta-analysis were rescue analgesic consumption in the 24-h postoperative period and rest pain scores. Results: Twelve trials (761 patients) were analyzed. Ketorolac-infiltration provided a clinically unimportant benefit in morphine consumption (mean difference, -2.81 mg; 95% confidence interval [CI], -5.11 to -0.50; p = 0.02; moderate-quality evidence). Low-to-moderate quality evidence supported a brief (2-6 h), clinically subtle, but statistically consistent effect of surgical site ketorolac-infiltration in reducing wound pain at rest. High-quality evidence supported shorter hospital stays for surgical patients receiving local ketorolac-infiltration when compared to controls (mean difference, -0.12 days; 95% CI, -0.17 to -0.08; p < 0.00001). Further, ketorolac-infiltration does not improve any opioid-related side effects. Innovation: Ketorolac-infiltration provides statistically significant but clinically unimportant benefits for improving postoperative wound pain. Conclusion: Overall, despite the fact that current moderate-to-high quality of evidence does not support routine using of ketorolac as an adjuvant to local anesthetic for wound infiltration, these findings underscore the importance of optimizing agents and sustained delivery parameters in postoperative local anesthetic practice. Clinical Trials.gov ID: CRD42021229095.

Effects of omega 3 polyunsaturated fatty acids, antioxidants, and/or non-steroidal inflammatory drugs in the brain of neonatal rats exposed to intermittent hypoxia.

Preterm infants experience frequent arterial oxygen desaturations during oxygen therapy, or intermittent hypoxia (IH). Neonatal IH increases oxidative distress which contributes to neuroinflammation and brain injury. We tested the hypotheses that exposure to neonatal IH is detrimental to the immature brain and that early supplementation with antioxidants and/or omega 3 polyunsaturated fatty acids (n-3 PUFAs) combined with non-steroidal anti-inflammatory drugs (NSAIDs) is protective. Newborn rats were exposed to brief hypoxia (12% O2 ) during hyperoxia (50% O2 ) from the first day of life (P0) until P14 during which they received daily oral supplementation with antioxidants, namely coenzyme Q10 (CoQ10) or glutathione nanoparticles (nGSH), n-3 PUFAs and/or topical ocular ketorolac. Placebo controls received daily oral olive oil and topical ocular saline. Room air (RA) littermates remained in 21% O2 from birth to P21 with all treatments identical. At P14 animals were allowed to recover in RA until P21 with no further treatment. Whole brains were harvested for histopathology and morphometric analyses, and assessed for biomarkers of oxidative stress and inflammation, as well as myelin injury. Neonatal IH resulted in higher brain/body weight ratios, an effect that was reversed with n-3 PUFAs and n-3 PUFAs+CoQ10 with or without ketorolac. Neonatal IH was also associated with hemorrhage, oxidative stress, and elevations in inflammatory prostanoids. Supplementation with n-3 PUFAs and nGSH with and without ketorolac were most beneficial for myelin growth and integrity when administered in RA. However, the benefit of n-3 PUFAs was significantly curtailed in neonatal IH. Neonatal IH during a critical time of brain development causes inflammation and oxidative injury. Loss of therapeutic benefits of n-3 PUFAs suggest its susceptibility to oxidation in neonatal IH and therefore indicate that co-administration with antioxidants may be necessary to sustain its efficacy.

Management of postoperative pain in ophthalmic plastic surgery: a major review.

PURPOSE: Clinicians are becoming increasingly aware of the risks of opioid analgesics, and, consequently, are searching for alternatives to these agents. This review considers the existing literature regarding the management of pain after ophthalmic plastic surgery. METHODS: A literature search was performed through the PubMed database. Articles were assessed for relevance, and the appropriate data was extracted from the medical literature regarding pain management strategies after oculoplastic procedures. RESULTS: An emerging body of literature suggests the efficacy of a variety of non-narcotic agents in post-operative pain management. Many of these medications prevent the development of pain, and several have been studied in randomized trials. Specifically, pregabalin, ketorolac, acetaminophen, memantine, local anesthetics, and alternative therapies all have documented benefit in this setting. CONCLUSIONS: Several medications may prevent and treat pain after ophthalmic plastic surgery. These agents are well-tolerated, and many decrease the requirement for opioid analgesics. Clinicians should be aware of these therapies when considering non-narcotic pain management.

Improving Acute Treatment of Pediatric Primary Headache Disorders With a Novel Headache Treatment Center: Retrospective Review of Preliminary Outcomes.

OBJECTIVE: To determine preliminary outcomes of targeted headache treatments provided at a novel outpatient acute care pediatric headache treatment center. BACKGROUND: Limitations exist in acute management of pediatric headaches, including inadequate access to specialty headache therapies and headache specialists in acute settings, variable success of emergency room treatments, and omission of comfort measures. An outpatient acute headache care clinic (the "Headache Treatment Center") was strategically initiated at a Midwestern pediatric academic hospital to provide acute and targeted headache therapies for children with active headaches. METHODS: We conducted a retrospective chart review of 154 visits from September through November 2018 of patients ages 7-18 years visiting the Headache Treatment Center. RESULTS: On average, headache intensity (measured on an 11-point pain numeric rating scale) decreased after interventions used in the Headache Treatment Center (mean change = 2.85 ± 2.81, P < .05, Cohen d = 1.01). Large effect sizes for reducing headache intensity were observed for pericranial, occipital/auriculotemporal, and occipital nerve blocks, Cohen d = 1.56, 1.64 and 1.02, respectively. Large effect sizes for reducing headache intensity also were observed for a transcutaneous supraorbital nerve stimulator device (Cefaly) (Cohen d = 1.02), acupuncture (Cohen d = 1.09), and intravenous migraine cocktails (Cohen d = 0.91-1.34). CONCLUSION: Targeted headache therapies to abort pediatric primary headaches as part of a novel headache clinic model may be beneficial for short-term management.

PENG block and LIA as a possible anesthesia technique for total hip arthroplasty.

The aim of this study is to evaluate the efficacy of the pericapsular nerve group block and local infiltration analgesia (LIA) combination as the only anesthesia technique for the total hip arthroplasty (THA). We considered the anesthetic plan, postoperative analgesia, hospital length of stay, functional recovery, bleeding, complications and the adverse events. We reported 10 ASA I-II patients admitted for elective primary THA, receiving LIA during (5) and at the end of surgery (5). For the PENG block we used a single injection of 40 ml levobupivacaine 0.25% and dexamethasone 4 mg. For LIA, a mixture of 0.25% levobupivacaine, ketorolac, epinephrine, and morphine was injected into periarticular tissues. The pain intensity was evaluated with a numeric rating scale. All patients were fully satisfied and improvement in pain relief, symptoms, and functional activity was remarkable. Intraoperative blood losses ranged 100-600 ml. No intraoperative complications or signs of toxicity occurred. The median duration of surgery was 59.5 ± 4.5 min and the hospital stay ranged between 2 and 3 days. PENG block and LIA could be hypothesized as an effective and safety anesthesia technique for the THA surgery, facilitating hip functional recovery and limit intraoperative blood losses and adverse events.

Preoperative stimulation of resolution and inflammation blockade eradicates micrometastases.

Cancer therapy is a double-edged sword, as surgery and chemotherapy can induce an inflammatory/immunosuppressive injury response that promotes dormancy escape and tumor recurrence. We hypothesized that these events could be altered by early blockade of the inflammatory cascade and/or by accelerating the resolution of inflammation. Preoperative, but not postoperative, administration of the nonsteroidal antiinflammatory drug ketorolac and/or resolvins, a family of specialized proresolving autacoid mediators, eliminated micrometastases in multiple tumor-resection models, resulting in long-term survival. Ketorolac unleashed anticancer T cell immunity that was augmented by immune checkpoint blockade, negated by adjuvant chemotherapy, and dependent on inhibition of the COX-1/thromboxane A2 (TXA2) pathway. Preoperative stimulation of inflammation resolution via resolvins (RvD2, RvD3, and RvD4) inhibited metastases and induced T cell responses. Ketorolac and resolvins exhibited synergistic antitumor activity and prevented surgery- or chemotherapy-induced dormancy escape. Thus, simultaneously blocking the ensuing proinflammatory response and activating endogenous resolution programs before surgery may eliminate micrometastases and reduce tumor recurrence.

How to diagnose and treat benign headaches.

A 19-year-old female, university student with a long-standing history of migraine headaches presented to the emergency department (ED) with a 36-hour history of gradual onset of left-sided headache, preceded by visual aura. She stated that her headache was worse than usual and now associated with nausea, vomiting, and photophobia, despite use of oral ibuprofen. On examination, she was afebrile, her SaO2 = 98% on room air, her pulse was 110 beats/minute, and she was breathing 20 breaths/minute. She received a Canadian Triage and Acuity Scale score of 2 due to her pain score of 8/10 on a Visual Analogue Scale (VAS). Her neurological examination was normal and her neck was supple with full range of motion. She was a non-smoker, infrequent cannabis user, and her last menstrual period was normal.

Functional Abdominal Pain in a Pediatric Patient After Resolution of Acute Pancreatitis: A Case Report.

Children with acute pancreatitis may develop chronic abdominal wall pain after resolution of clinical, laboratory, and radiographic signs of disease. We describe a 13-year-old boy who underwent an unrevealing, complex diagnostic evaluation for persistent abdominal pain after resolution of acute pancreatitis. His pain required an extended leave of absence from school and nasogastric tube feeds. After receiving abdominal nerve blocks and trigger point injections, he experienced near-complete resolution of pain with normalization of eating habits and daily function. Pain practitioners should think critically about the signs and symptoms of visceral versus somatic pain and try newer diagnostic interventions that may be therapeutic.

Parturient on Magnesium Infusion and Its Effectiveness as an Adjuvant Analgesic after Cesarean Delivery: A Retrospective Analysis.

BACKGROUND: Perioperative use of intravenous magnesium as part of multimodal analgesia has been increasing in recent years in an effort to decrease the use of opioids. The aim of this study was to evaluate the effectiveness of magnesium sulfate infusion in lowering analgesic requirement and decreasing the intensity of pain score after cesarean delivery. METHODS: Sixty-four patients who underwent cesarean delivery under spinal anesthesia were included in this medical record review: 32 patients received magnesium infusion after cesarean delivery for treatment of mild preeclampsia (Mg group); 32 patients received routine post-cesarean delivery care (control group). Primary outcome was total analgesic consumption and secondary was visual analogue scores (VAS) of pain in each group during the first 24 hours following delivery. These measures were compared using Student's t-tests and Mann-Whitney U-tests. RESULTS: Our study found that patients in the Mg group had significantly less requirement for analgesia than the control group. In the 24 h after cesarean delivery, the Mg group received significantly less intravenous ketorolac (the standard initial rescue analgesic agent) when compared to the control group (79 ± 23 mg vs. 90 ± 0 mg; P = 0.008). The Mg group also received significantly less intravenous morphine equivalents than the control group (median 5.0 (IRQ: 0.0 - 10.0) vs. 9.3 (IRQ: 6.0 - 21.1); P = 0.001) during the first 24 h after cesarean delivery. The Mg group also had significantly lower VAS pain scores than the control group (median 1.75 (IRQ: 0.4 - 2.6) vs. median 3.2 (IRQ: 2.3 - 4.5); P < 0.001). CONCLUSIONS: Our results suggest that magnesium sulfate infusion decreases total analgesic requirements and lowers VAS pain scores during the first 24 h after cesarean delivery.

Magnetic field distribution modulation of intrathecal delivered ketorolac iron-oxide nanoparticle conjugates produce excellent analgesia for chronic inflammatory pain.

BACKGROUND: Nanoparticles have become one of the most promising among the potential materials used for biomedical applications. However, few researchers have focused on their effects on analgesia. Despite the fact that various nanoparticles have been evaluated for drug delivery and MRI imaging contrast enhancement in clinical settings, no reports have investigated the in vivo synergy of ketorolac iron-oxide nanoparticle conjugates to improve the analgesic effect. METHODS: Ketorolac conjugated magnetic iron oxide nanoparticles (Keto-SPIO) were synthesized via two-stage additions of protective agents and chemical co-precipitation. ICR mice were used to develop inflammatory pain models induced by Complete Freund's adjuvant (CFA) injection in the hind paw. Different magnet field strengths and polarities were applied to the spinal cord after injecting Keto-SPIO into the theca space. Analgesia behavior was evaluated with the up-down method via von Frey microfilament measurement. Spinal cord tissues were harvested at the end analgesia time point upon induction of the inflammatory pain. The presence of the two cyclooxygenases (COX) in the spinal cord was examined via Western blotting to quantify the changes after intra-thecal Keto-SPIO administration. RESULTS: Intrathecal Keto-SPIO administration demonstrated a magnetic field-dependent analgesia effect in CFA pain model with a significant reduction in COX expression. CONCLUSIONS: Our results indicated that intrathecal administration of the Keto-SPIO combined magnet field modulated delivery significantly promoted an analgesia effect with suppression of COX in the mice inflammatory pain model.

Local infiltration analgesia or femoral nerve block for postoperative pain management in patients undergoing total hip arthroplasty. A randomized, double-blind study.

BACKGROUND AND AIMS: Several methods for pain management following total hip arthroplasty (THA) have been described but the best postoperative pain management technique remains uncertain. We compared surgeon applied local infiltration analgesia (LIA) with anaesthesiologist performed femoral nerve block (FNB) using ultrasound. The primary aim was to assess pain intensity 24h after THA. METHODS: In this randomized, double-blind study, 56 patients (ASA I-III) undergoing THA consented to participate. In Group FNB, patients received an ultrasound-guided femoral nerve block using 30ml of ropivacaine 7.5mg/ml (225mg) while Group LIA received a similar volume of saline. Spinal anaesthesia was then performed and bupivacaine heavy, 3-3.5ml injected depending on patient characteristics. During surgery, patients in Group LIA received a mixture of 300mg (150ml) ropivacaine, ketorolac 30mg (1ml) and adrenaline 0.5mg (0.5ml) (total volume 151.5ml) peri-articularly and subcutaneously while Group FNB received 151.5ml of saline peri-articularly in a systematic way by the surgeon. A multi-hole catheter was placed with the tip placed intra-articularly at the end of surgery in both groups. After 23h, the LIA mixture consisting of 20ml ropivacaine (7.5mg/ml), ketorolac 30mg (1ml), adrenaline 0.1mg (1ml) (total volume 22ml) was injected in Group LIA and the same volume of saline in Group FNB. Postoperative pain, analgesic consumption (postoperative and post-discharge), side effects, home discharge, quality of life and hip function were recorded, the latter up to 6 months after surgery. RESULTS: Postoperative pain intensity was significantly lower in Group LIA compared to Group FNB during mobilization at 24h (primary endpoint), mean difference 1.8 NRS units (95% CI 0.7-2.9) (P=0.006), at rest after 4h (P=0.029) and on standing after 24 (P=0.0003) and 48h (P=0.043). Rescue morphine consumption was also significantly lower in Group LIA during 0-24, mean difference 13.5mg (95% CI, 6.1-20.9) (P=0.002) postoperatively. Motor block was greater at 6h (P=0.029) postoperatively in Group FNB. Two patients (one in each group) had persistent post-surgical pain (NRS>3) at 3 months (3.6%) but none at 6 month. No other differences were found between the groups. CONCLUSION: Local infiltration analgesia significantly reduces pain intensity on standing and mobilization, and rescue analgesic consumption compared to femoral nerve block without causing significant side effects. The superior analgesia in the LIA group may result from the secondary injection at 23h postoperatively and needs to be further evaluated in future studies. No differences were found in home discharge, quality of life and hip dysfunction between the groups. IMPLICATION: Local infiltration analgesia is the preferred method for postoperative pain management following THA compared to single-shot femoral nerve block.

Synergistic antinociceptive interaction of Syzygium aromaticum or Rosmarinus officinalis coadministered with ketorolac in rats.

Syzygium aromaticum (L.) Merr. & L.M. Perry (Mirtaceae) and Rosmarinus officinalis L. (Lamiaceae) are both medicinal plants used for centuries to alleviate pain. The aim of the study was to demonstrate the therapeutic potential utility of herb-drug association of S. aromaticum essential oil or R. officinalis ethanolic extract coadministered with ketorolac. Antinociceptive pharmacological interaction was investigated by an isbolographic study using the formalin test in rats. Both alone and in combination with ketorolac; S. aromaticum and R. officinalis produced a dose-dependent antinociceptive response. To plot the isobologram, we used the effective dose 50 of each one component in a fixed 1:1 ratio. The isobolographic analysis showed that, in both combinations, ketorolac plus essential oil S. aromaticum and ketorolac plus ethanolic extract R. officinalis, the experimental value (Zexp) was lower than the theoretical value (Zadd). In addition, this study shows that eugenol, a metabolite present in S. aromaticum, and ursolic acid, a metabolite present in R. officinalis, also synergized the antinociceptive effect of ketorolac. While, the oleanolic acid present in both medicinal species did not show a synergistic antinociceptive effect in combination with ketorolac. No adverse effects were observed with these herb-drug interactions. These findings suggest that essential oil S. aromaticum and ethanolic extract R. officinalis could be useful in combination with ketorolac for the treatment of inflammatory pain.

[Management of ureteric colic with ketorolac and nifedipin vs. ketorolac and tamsulosin in the emergency room]. / Manejo del cólico ureteral con ketorolaco y nifedipina frente a ketorolaco y tamsulosina en el servicio de urgencias.

BACKGROUND: Ureteric colic is the most common symptom of lithiasis. It is caused by the presence of stones accumulated in the renal papillae. These stones often migrate down the ureter, causing a ureteric colic, characterized by a severe pain in the lumbar region. The aim of this study was to compare the use of ketorolac and nifedipine vs. ketorolac and tamsulosin for the medical treatment of pain caused by stones in the lower ureter. METHODS: Longitudinal study of 150 patients of 21-years or older with stones in the lower third of the ureter. 50% received ketorolac and nifedipine and the other 50%, ketorolac and tamsulosin. The Numeric Pain Rating Scale (NPRS) was used for the assessment of pain at admission and 4 and 12 hours after the treatment was administered. We used descriptive and inferential statistics (Mann-Whitney-Wilcoxon, chi-squared and Poisson regression). RESULTS: Mean age was 38.17 years; 54.7% were male and 45.3% female. NPRS mean was 9.69 (initially), 7.42 (at 4 hours) and 2.05 (at 12 hours). There were no significant differences in the initial measurement of pain between groups (p < 0.005); four and 12 hours later the pain decreased more in patients managed with ketorolac and nifedipine, p = 0.0041. There were no complications nor side effects in both treatments. CONCLUSION: The use of ketorolac and nifedipine is more effective than the use of ketorolac and tamsulosin for the management of pain caused by lower ureteral colic during the first 12 hours of treatment.

Introducción: el cólico renoureteral es la manifestación más común de la litiasis. Se trata de la presencia de cálculos en las papilas renales que frecuentemente migran hacia el uréter, ocasionando un cólico renoureteral, caracterizado por un dolor intenso en la región lumbar o en sus flancos. Se buscó comparar el uso del ketorolaco y nifedipino frente a ketorolaco y tamsulosina para el manejo del dolor ocasionado por litiasis en el tercio inferior del uréter. Métodos: estudio longitudinal en 150 pacientes mayores de 21 años con litiasis en tercio inferior del uréter. Al 50% se le administró ketorolaco y nifedipino y al otro 50% ketorolaco y tamsulosina. Se utilizó la escala numérica de dolor (END) al ingreso, a las 4 y a las 12 horas. La estadística fue descriptiva e inferencial (U de Mann-Whitney-Wilcoxon, chi cuadrada y regresión de Poisson). Resultados: la edad promedio fue 38.17 años y 54.7% de los pacientes fueron hombres. Inicialmente la END tuvo una media de 9.69, de 7.42 a las 4 horas y de 2.05 a las 12 horas. En la medición inicial del dolor no hubo diferencias significativas entre ambos grupos (p > 0.005); 4 y 12 horas después el dolor disminuyó más en los pacientes manejados con ketorolaco y nifedipino: p = 0.0041 y p = 0.000, respectivamente. No hubo complicaciones ni efectos secundarios en ambos tratamientos. Conclusión: la mancuerna ketorolaco y nifedipino es más efectiva que la del ketorolaco y la tamsulosina para el manejo del dolor del cólico renoureteral inferior durante las primeras 12 horas de tratamiento.

Can local infiltration analgesia increase satisfaction in postoperative short-term pain control in total knee arthroplasty?

BACKGROUND: One of the major challenges to total knee arthroplasty (TKA) is optimal pain control. Effective analgesia is capital in fast-track surgery programs to allow patient's early functional outcomes. OBJECTIVES: Compare length of stay (LOS) short-term pain control, and patients' satisfaction at 1 month between local infiltration analgesia (LIA) combined with femoral nerve block (FNB) and FNB only in patients undergoing TKA. PATIENTS AND METHODS: Two hundred and fifty-four patients were included in a randomized prospective study and distributed in two groups. The first group received an intraoperative LIA (150 mL mixture of ropivacaine 2.0 mg/mL + ketorolac 30 mg + adrenaline 10 µg/mL) combined to an FNB. The control group had only an FNB. Demographical data and visual analog scale (VAS) score were obtained preoperatively, at 36 h after surgery and at the 15-day follow-up. Patients' satisfaction at 1 month was also evaluated. Statistical analysis data was performed. RESULTS: No differences in demographical data and preoperative VAS score were observed between both groups. LIA group had a lower VAS score at 36 h after surgery (1.34 ± 1.31 vs. 3.68 ± 1.932 in the control group, p = 0.00), but these differences were not maintained at the 15-day follow-up (4.51 ± 1.889 vs. 4.11 ± 1.940 in the control group, p > 0.05). LOS and patients' satisfaction were comparable between groups. Patients with LIA had no additional complications. CONCLUSIONS: LIA is a safe adjuvant to FNB to reduce perioperative pain during the first 36 h after TKA. Its effects wean with time, but do cover the first crucial hours of rehabilitation in a fast-track program. LIA seems don't modify postoperative course nor patient's satisfaction at short-term follow-up. The final impact of LIA on surgical outcome is still to be determined.

Prospective randomized controlled trial comparing standard analgesia with combined intra-operative cystic plate and port-site local anesthesia for post-operative pain management in elective laparoscopic cholecystectomy.

BACKGROUND: Various mechanisms, including somatic and visceral nociceptive stimulation, have been suggested as a cause for pain after laparoscopic cholecystectomy (LC). We therefore conducted a prospective randomized controlled trial (PRCT) to evaluate whether somatovisceral pain blockade reduces pain after LC. HYPOTHESIS: Analgesic efficacy of multimodal analgesia is superior to standard analgesia for patients undergoing elective LC for symptomatic cholelithiasis. Specifically, topical cystic plate and port-site injection with 0.25 % bupivacaine significantly reduces pain after LC. DESIGN: This study was designed as single-blinded PRCT. SETTING: This study was conducted in an academic medical center. PATIENTS AND METHODS: Between February and May 2010 we randomly assigned 63 patients with symptomatic cholelithiasis in a 1:1 ratio to non-opioid/opioid analgesic combinations (Control Group, n = 32) and non-opioid/opioid analgesic combinations plus topical 0.25 % bupivacaine onto the cystic plate and local 0.25 % bupivacaine port-site injection, post-LC (Study Group, n = 31). Primary endpoint was patient-reported pain 1, 4, 6, 12, 24 h and 1 week post-LC using the Visual Analog Scale (VAS 0-10). RESULTS: Study groups were comparable clinicopathologically. There were no adverse events. A statistically significant reduction in mean pain score was apparent in Study Group patients in comparison with Control Group (mean VAS 4.83 ± 2.33 vs. 6.80 ± 1.87; p < 0.001) at all early (1-6 h) post-operative time points following LC. CONCLUSION: This PRCT shows significantly improved pain control with somatovisceral pain blockade over non-opioid/opioid analgesic combinations following LC for symptomatic cholelithiasis. For centers not utilizing adjunctive local anesthetic for LC, this topical use of bupivacaine may improve patient comfort during recovery. This trial was registered on www.ClinicalTrials.gov NCT# 01972620.