Combined Analgesia Research Articles

Multimodal analgesics after adult cardiac surgery; a systematic review

Abstract Background Moderate to severe pain is frequently reported during the acute recovery phase following adult cardiac surgery. Multimodal analgesics are recommended for adult patients post cardiac surgery, but the optimal combination of multimodal analgesics is unknown. Purpose To synthesise the best available evidence about the effectiveness of multimodal analgesics on pain after adult cardiac surgery. Methods A systematic review was conducted according to the PRISMA-P statement and the published review protocol. Inclusion criteria were full-text papers or abstracts with adequate reporting, in any language, of randomised controlled trials (RCTs) in adult patients undergoing cardiac surgery that investigated the effect of multimodal postoperative analgesic regimens, compared to a control group. The highest mean level of patient self-reported pain intensity at rest, captured using a validated pain assessment tool, was the primary outcome measure. Results Of 3754 citations identified in the initial search to the 12th of December 2022, there were 1605 duplicates leaving 2149 citations for title and abstract screening, of which 2027 were irrelevant. There were 122 full-text papers assessed and 29 included in the review. Data were independently extracted by 2 reviewers in Covidence®. Participants (N = 2360), aged 59.5 + 8.2 years, were primarily male (N = 1561, 66.1%), weighing 78.1 +9.2 kilograms. Risk of bias was high and reporting quality was poor. Pain at rest reported in 18 (62%) studies was 3.5 (SD 1.2) in the control and 2.7 (SD 0.9) in the intervention groups respectively. Nurse-led versus patient-controlled analgesic administration was tested in 14 (48.3%) trials. All trials tested different analgesic combinations, none of which compared a combination of non-opioids, opioid agonist-antagonist agents, or full opioid agonists. Conclusions Poorly managed pain is associated with postoperative complications, unplanned readmissions, and the development of chronic pain. Robust RCTs are urgently needed to inform optimal combinations of multimodal analgesics to optimise patient recovery after adult cardiac surgery.Risk of Bias

Efficacy and Safety of Fixed-Dose Combinations for Pain in Older Adults.

Pain is common in older adults and managing pain in this population can be challenging owing to altered pharmacokinetics, multimorbidity, polypharmacy, cognitive impairment, and physical frailty. A fixed-dose combination (FDC) analgesic contains two or more pharmaceutical ingredients in a single pill and may offer more benefits when compared with loose-dose formulations. The benefits include reduced pill burden and better adherence, a broader analgesic spectrum well-suited to multimechanistic pain conditions and more predictable pharmacokinetic and pharmacodynamic properties. These advantages may outweigh disadvantages such as reduced flexibility in dose adjustment. Most of the commonly used FDC analgesics are made up of a combination of paracetamol, muscle relaxant, nonsteroidal anti-inflammatory drug or opioid. They have been shown to have better efficacy and similar safety profiles compared with individual drugs. Adverse effects from the use of FDC analgesics in older patients were comparable with that observed in younger populations. With proper patient selection and continuous surveillance, FDC analgesics will likely benefit older adults by simplifying dosing regimen and improving compliance.

Propofol-alone sedative efficacy in observational biliopancreatic endoscopic ultrasound.

Appropriate sedative and analgesic selection is essential to reduce patient discomfort and body movement to safely conduct endoscopic ultrasonography (EUS). However, few cases have examined sedation with propofol in EUS, and few studies the need for combined analgesia. In this study, we retrospectively evaluated the usefulness and safety of propofol without analgesics for sedation in biliopancreatic observational EUS. This single-center retrospective study included 516 observational biliopancreatic EUS procedures using propofol alone performed between April 2021 and March 2023. The primary and secondary endpoints were the observational biliopancreatic EUS results obtained with propofol alone and adverse event occurrence, respectively. The median examination time and total propofol dose were 22 (range: 10-67) min and 186.5 (range: 50-501) mg, respectively. The median starting Richmond Agitation-Sedation Scale and Visual Analog Scale scores were -5 (range: -5-1) and 0 (range: 0-10), respectively. The median recovery time was 22 (range: 5-80) min. Adverse events occurred in 60 (11.6%) patients. Trainee-performed examination (odds ratio [OR] 3.52, 95% confidence interval [CI]: 1.63-7.60, p = 0.0014) and examination length (>22 min; OR 1.67, 95% CI: 0.95-2.92, p = 0.07) were risk factors for adverse events.High body mass index (OR 1.87, 95% CI: 1.10-3.16, p = 0.02) and extended examination time (OR 4.23, 95% CI: 2.08-8. 57, p < 0.001) were risk factors for delayed recovery. During observational biliopancreatic EUS, propofol is useful as a single sedative and offers high patient satisfaction and relative safety.

A Systematic Review of Pharmacological Interventions for Chronic Pain Management

Estimates suggest that around 1.5 billion people worldwide suffer from chronic pain, exacerbated by aging demographics. Chronic conditions are linked to additional health issues and reduced quality of life, highlighting the importance of effective treatments. Our study reviewed current pharmacological interventions for chronic pain management using databases like CNKI, CBM, and Embase. Meta-analysis indicated significant pain reduction with compound analgesics compared to opioids, non-opioids, and placebos. Results suggest high efficacy in treating nociplastic, neuropathic, and nociceptive pain. Chronic pain is a significant public health issue requiring effective pharmacological treatments with better side-effect profiles to enhance therapeutic recommendations. A systematic understanding of pain prevalence among healthcare providers, policymakers, and researchers is crucial for addressing socioeconomic factors that aggravate the issue.

Lyme disease in companion animals: an updated state-of-art and current situation in Portugal.

Lyme disease (LD) is a globally distributed zoonotic multisystemic condition caused by gram-negative spirochete bacteria of the Borrelia burgdorferi complex, transmitted through tick bites. Research on LD in domestic animals in Portugal is limited, potentially leading to underestimating its prevalence. This disease affects many species, including humans, making it a critical public health issue. In domestic animals, LD often presents subclinically or with non-specific clinical signs, complicating its diagnosis. Nevertheless, veterinarians should always consider LD in cases with a history of tick exposure and compatible clinical signs. Diagnostic confirmation can be achieved through serological and other complementary tests. Treatment involves eradicating the bacterial infection and managing clinical signs using a combination of antibiotics, analgesics, anti-inflammatories, and other medications. Effective prevention primarily relies on tick control measures. This review aims to provide an up-to-date state-of-the-art LD, particularly in Portugal.

Multimodal Analgesia Approach in Acute Low Back Pain Management: A Phase III Study of a Novel Analgesic Combination of Etoricoxib/Tramadol.

Pain and disability management are crucial for a speedy recovery. Combining analgesics with different mechanisms of action provides greater pain relief with lower doses, promoting efficient multimodal analgesia. This study evaluated the efficacy and safety between two fixed-dose combinations (FDC): etoricoxib/tramadol compared to paracetamol/tramadol for the management of acute low back pain (LBP) in a 7-day treatment. We conducted a phase IIIb, prospective, randomized, and multicenter study in patients with acute LBP treated with etoricoxib 90mg/tramadol 50mg (one packet of granules diluted in 100ml of water, once a day [QD], for 7 days) or paracetamol 975mg/tramadol 112.5mg (one tablet of 325mg/37.5mg, three times a day [TID], for 7 days) to assess the efficacy (in terms of pain and disability improvement) and safety. One hundred and twenty-four patients were randomized to receive either etoricoxib/tramadol QD (n = 61) or paracetamol/tramadol TID (n = 63). From the magnitude of change in pain evaluations, differences were observed between the treatment groups at 3 [p = 0.054, CI 95% -0.648 (-0.010 to 1.306)] and 5days (p = 0.041). The proportion of patients with a 30% reduction in Visual Analogue Scale (VAS) score was statistically significant when comparing the treatment groups on the third day of follow-up [p = 0.008, CI 95% 0.241 (0.061-0.421)]. An improvement in LBP's disability to perform activities of daily routine (Oswestry and Roland-Morris questionnaires) was observed in both treatment groups. A total of 79 adverse events (AEs) (38 [48.1%] with etoricoxib/tramadol and 41 [51.9%] with paracetamol/tramadol) were reported. The most frequent AEs were nausea (17.7%) and dizziness (16.4%). The results show the clinical benefits of etoricoxib/tramadol FDC, such as the sparing effect of tramadol dose per day, early therapeutic response rate compared with paracetamol/tramadol; which translates into faster pain relief, better adherence, less tramadol drug dependency, and a reduction of related AEs incidence. ClinicalTrials.gov identifier, NCT04968158.

Efficacy of a Multimodal Surgical Site Injection for Postoperative Pain Control in Pediatric Patients With Cerebral Palsy Undergoing Hip Reconstruction: A Randomized Controlled Trial.

One in 4 children with cerebral palsy (CP) will undergo orthopaedic surgery during their childhood. Despite its ubiquity, postoperative pain control has been poorly studied in this patient population. Moreover, poor pain management has been associated with adverse surgical outcomes. Multimodal analgesic injections have been well studied in the adult population, demonstrating safety and efficacy in reducing postoperative pain and narcotic consumption, but this modality has not been studied in pediatric patients undergoing similarly complex procedures. The objective of this study was to evaluate the efficacy of a multimodal surgical site injection for postoperative pain control following operative management of hip dysplasia in patients with CP. After obtaining IRB approval, a multicenter, randomized double-blind placebo control trial was completed. Patients below 18 years old with a diagnosis of CP who were scheduled for varus derotation osteotomy (VDRO) of the proximal femur were randomized to receive a surgical-site injection with either a combination of ropivacaine (3mg/kg), epinephrine (0.5mg), and ketorolac (0.5mg/kg) (experimental group) or normal saline (control). All included patients had identical postoperative care, including immobilization, physical therapy, and standardized, multimodal postoperative pain control. Pain scores and narcotic consumption were recorded at regular intervals and compared between groups utilizing two-tailed t test or a nonparametric Mann-Whitney test for quantitative variables and a Fischer exact test for categorical variables. Thirty-four patients were included, evenly divided between study arms. There were no significant differences in demographic variables, gross motor function classification system (GMFCS), comorbidities, preoperative radiographic parameters, or concomitant surgeries between groups. Patients in the experimental group required significantly lower narcotic medications at all postoperative time points from PACU until hospital discharge compared with controls (0.41 ± 0.42 vs. 1.87 ± 2.05 total morphine mEQ/kg, P=0.01). Similarly, patients in the experimental group were found to have significantly lower pain scores throughout their hospital stays compared with controls (1.0 ± 0.6 vs. 2.4 ± 1.1 mean pain score, P<0.001). There were no significant differences in operative time, OR time, blood transfusion requirements or hospital length of stay between groups. There were no adverse medication reactions or injection site complications in either group. In patients with CP undergoing hip reconstruction, surgical-site injection with a multimodal analgesic combination improves pain control and reduces narcotic consumption in the early postoperative period with no observed adverse effects. Local multimodal analgesic injections should be adopted as part of standard multimodal pain control in this patient population for all osseous surgeries. Level I-therapeutic.

Occurrence of somnolence and respiratory depression induced by pregabalin and mirogabalin use and the influence of opioid treatment using the Japanese adverse drug event report database.

Background: Gabapentinoid anticonvulsants are standard treatment for neuropathic pain and are often combined with opioids for treating cancer. It is assumed that this combination may heighten somnolence and respiratory depression due to the inhibitory effects of opioids on the central nervous system. Although pregabalin, a gabapentinoid, is known to increase somnolence frequency during opioid therapy, whether mirogabalin exerts similar effects on somnolence frequency under opioid therapy remains unknown. This study examined the signals of somnolence and respiratory depression in response to pregabalin and mirogabalin use by utilizing data from the Japanese Adverse Drug Event Report database and assessed their interaction with strong opioid analgesics. Methods: Information was obtained from the JADER database from April 2004 to August 2023 via the Pharmaceuticals and Medical Devices Agency website. The study focused on neuropathic pain medications, specifically "pregabalin" and "mirogabalin besilate." Adverse events were defined using preferred terms (PTs) from the Medical Dictionary for Regulatory Activities version 26.1. The PTs considered were "Somnolence (10041349)" and "Respiratory depression (10038678)." To investigate the effect of the combination of strong opioid analgesics with pregabalin and mirogabalin on the occurrence of somnolence, a multivariable logistic regression analysis was conducted. Results: Signals for somnolence were detected with the use of both drugs (pregabalin: information component (IC) [95% confidence intervals (CIs)]: 2.89 [2.70 to 3.08]; mirogabalin: IC [95% CIs] 2.50 [1.85 to 3.16]). When evaluating respiratory depression, a typical and serious adverse event of opioid analgesic use, a signal was detected with pregabalin use but not with mirogabalin use (pregabalin: (IC [95% CIs] 1.28 [0.83 to 1.73]; mirogabalin: IC [95% CIs] -0.15 [-2.20 to 1.89]). Multivariable analysis indicated that the use of strong opioid analgesics increased the occurrence of somnolence when combined with pregabalin but not when combined with mirogabalin (p = 0.004). Conclusion: While the safety of concomitant administation of mirogabalin with opioids remains controversial, caution should be exercised when using pregabalin, especially in combination with opioids for neuropathic pain, compared to that for mirogabalin.

Evaluation of Post-Operative Pain Management Techniques in Oral Surgery

ABSTRACT Objective: This prospective research directed to estimate the efficacy and safety of different post-operative pain management techniques in oral surgery subjects. Methods: Patients scheduled for various oral surgical procedures were recruited from a single oral surgery clinic between January 2022 and December 2023. Inclusion criteria encompassed adult subjects undergoing elective oral surgery under local or general anesthesia. Subjects were randomly assigned to one of three post-operative pain management protocols: Group A received standard analgesics, Group B received combination analgesics, and Group C received non-pharmacological interventions. Pain intensity scores, analgesic consumption, adverse events, and patient satisfaction were assessed at specified intervals post-operatively. Results: Non-pharmacological interventions demonstrated lower pain intensity scores and analgesic consumption compared to standard and combination analgesics. Additionally, the incidence of adverse events was lower in the non-pharmacological intervention group. Statistical analysis revealed significant differences in pain outcomes among the three groups. Conclusion: This prospective research suggests that non-pharmacological interventions may provide effective pain relief with fewer adverse events compared to traditional analgesics in post-operative oral surgery subjects. Implementation of multi-modal pain management approaches tailored to individual patient needs may improve overall pain control and enhance patient outcomes.

Hydromorphone combined with ropivacaine for erector spinae plane block in patients undergoing modified radical mastectomy: A prospective randomized controlled trial.

Combining hydromorphone with ropivacaine in ultrasound-guided erector spinae plane blocks enhances postoperative analgesia and reduces interleukin-6 expression in breast surgery patients. In this study, breast cancer patients undergoing modified radical mastectomy were randomized into 3 groups for anesthesia (30 patients in each group): standard general (group C), Erector Spinae Plane Block (ESPB) with ropivacaine (group R), and ESPB with ropivacaine plus hydromorphone (group HR). Diagnosis: Breast cancer patients. Postsurgery, pain levels, IL-6, anesthetic doses, additional analgesia needs, and recovery milestones were compared to evaluate the efficacy of the ESPB enhancements. The 3 groups were not significantly different in baseline characteristics, operation time, number of cases with postoperative nausea, and serum IL-6 concentrations at T1 (the time of being returned to the ward after surgery). At T2 (at 6:00 in the next morning after surgery), the serum IL-6 concentration in group HR was significantly lower than that in groups R and C (P < .05); the intraoperative doses of remifentanil, sufentanil, and propofol were significantly lower in groups HR and R than those in group C (P < .05); Groups HR and R had significantly lower visual analog scale scores at T3 (4 hours postoperatively), T4 (12 hours postoperatively), and T5 (24 hours postoperatively) than those in group C (P < .05); the proportions of patients receiving postoperative remedial analgesia were significantly lower in groups HR and R than in group C (P < .05); groups HR and R had significantly lower proportions of patients with postoperative nausea than group C (P < .05); the time to the first anal exhaust and the time to the first ambulation after surgery were significantly shorter in groups HR and R than those in group C (P < .05). Hydromorphone combined with ropivacaine for ESPB achieved a greater postoperative analgesic effect for patients receiving MRM under general anesthesia. The combined analgesia caused fewer adverse reactions and inhibited the expression level of the inflammatory factor IL-6 more effectively, thereby facilitating postoperative recovery. ESPB using hydromorphone with ropivacaine improved pain control post-MRM, reduced adverse effects, and more effectively suppressed IL-6, enhancing recovery.

MATHEMATICAL PREDICTION OF CHANGES IN THE LEVELS OF CD40-CD40L TRANSMEMBRANE PROTEIN SYSTEM ACROSS DIFFERENT ANALGESIA TECHNIQUES IN CHILDREN

The impact of the CD40-CD40L on the development of non-communicable neurological conditions is determined by abnormal CD40 expression and may be detrimental to nervous tissue function. Pain is one of the earliest psychophysical functions to develop. Postoperative complications causing pain should be addressed immediately. Regional analgesia techniques can speed up children’s recovery and reduce the need for opioids. They can also lower the incidence of postoperative nausea and vomiting, respiratory complications, and postsurgical pain intensity.The aim of this study was to present a mathematical model that predicts changes in CD40-CD40L levels in children who underwent surgery under various analgesic modalities within the fi rst fi ve days postoperatively. The autoregressive probability model was used to predict the behavior of the experimental data function within 29 days after surgery.Material and Methods. The children were divided into three groups. Group I consisted of 33 children who underwent anterior abdominal wall surgery under general anesthesia with morphine. Group II comprised 27 children who underwent anterior abdominal wall surgery under general anesthesia with the transversalis fascia plane block (TFPB). Group III included 27 children who underwent anterior abdominal wall surgery under general anesthesia with the TFPB, combined with the quadratus lumborum block 4 (QLB-4) via a single injection. The serum CD40L levels were evaluated using the immunoenzymatic assay method. The autoregressive model method based on the Burg algorithm was used to predict the behavior of the experimental data function. To automate the calculation of predictions based on the Burg method, the ‘predict’ function in РТС MathCad Prime 7.0 software was used. All clinical and laboratory studies were conducted in accordance with the World Medical Association Declaration of Helsinki ‘Ethical Principles for Medical Research Involving Human Subjects’. The study is a fragment of the research project of the Department of Children Diseases of Postgraduate Medical Education Faculty, Ivano- Frankivsk National Medical University «Health Status and Adaption of Children from the Precarpathian Region with Somatic Diseases, Their Prevention» 2021-2026, state registration number 0121U111129.Results. On the fi fth day after surgery, the serum CD40-CD40L levels were highest in children who received conventional opioid analgesia. There was no signifi cant diff erence observed between children in the TFPB and TFPB+QLB groups. On the 29th day after surgery, the predicted CD40-CD40L levels were lowest in children who received conventional opioid analgesia combined with the TFPB+QLB.Conclusions. The fi ndings obtained confi rmed the positive eff ect of combined analgesia using opioids and regional nerve block TFPB+QLB in children who received anterior abdominal surgery on suppressing immune mechanisms of pain syndrome involving the CD40-CD40L signaling system.

Lidocaine and Ketamine as Sedation for Burn Wound Care in a Pediatric Patient: A Case Report

This is a case report of a developmentally healthy 14-month-old female with partial thickness scald burns at multiple sites (the face, trunk, and bilateral upper extremities) that covered 14% of her total body surface area. Novel procedural pain therapy using intravenous lidocaine and oral ketamine was administered to perform daily wound care with minimal discomfort. Following this daily analgesic protocol there was sufficient analgesia and sedation with no adverse side effects. Currently, there are no studies where this analgesic combination was used during burn wound care and dressing changes in pediatric cases. The success of this protocol in a pediatric case highlights the safety and efficacy of oral ketamine when used in conjunction with intravenous lidocaine which potentially allows for a lower dose per procedure and a reduced risk of adverse effects.

Non-opioid analgesic combinations following total hip arthroplasty (RECIPE): a randomised, placebo-controlled, blinded, multicentre trial

Multimodal postoperative analgesia following total hip arthroplasty is recommended, but the optimal combination of drugs remains uncertain. The aim of the RECIPE trial was to investigate the relative benefit and harm of the different combinations of paracetamol, ibuprofen, and the analgesic adjuvant dexamethasone for treatment of postoperative pain following total hip arthroplasty. The RECIPE trial was a randomised, blinded, placebo-controlled trial conducted at nine Danish hospitals. Adults scheduled for total hip arthroplasty were randomly assigned (1:1:1:1) using a computer-generated list with stratification by site to receive combinations of oral paracetamol 1000 mg every 6 h, oral ibuprofen 400 mg every 6 h, or a single-dose of intravenous dexamethasone 24 mg in the following groups: paracetamol plus ibuprofen, ibuprofen plus dexamethasone, paracetamol plus dexamethasone, and paracetamol plus ibuprofen plus dexamethasone. The primary outcome was 24 h intravenous morphine consumption, analysed in a modified intention-to-treat population, defined as all randomly assigned participants who underwent total hip arthroplasty. The predefined minimal important difference was 8 mg. Safety outcomes included serious and non-serious adverse events within 90 days and 24 h. The trial was registered with ClinicalTrials.gov, NCT04123873. Between March 5, 2020, and Nov 15, 2022, we randomly assigned 1060 participants, of whom 1043 (589 [56%] women and 454 [44%] men) were included in the modified intention-to-treat population. 261 were assigned to paracetamol plus ibuprofen, 262 to ibuprofen plus dexamethasone, 262 to paracetamol plus dexamethasone, and 258 to paracetamol plus ibuprofen plus dexamethasone. Median 24 h morphine consumption was 24 mg (IQR 12-38) in the paracetamol plus ibuprofen group, 20 mg (12-32) in the paracetamol plus dexamethasone group, 16 mg (10-30) in the ibuprofen plus dexamethasone group, and 15 mg (8-26) in the paracetamol plus ibuprofen plus dexamethasone group. The paracetamol plus ibuprofen plus dexamethasone group had a significantly reduced 24 h morphine consumption compared with paracetamol plus ibuprofen (Hodges-Lehmann median difference -6 mg [99% CI -10 to -3]; p<0·0001) and paracetamol plus dexamethasone (-4 mg [-8 to -1]; p=0·0013), however, none of the comparisons showed differences reaching the minimal important threshold of 8 mg. 91 (35%) of 258 participants in the paracetamol plus ibuprofen plus dexamethasone group had one or more adverse events, compared with 99 (38%) of 262 in the ibuprofen plus dexamethasone group, 103 (39%) of 262 in the paracetamol plus dexamethasone group, and 165 (63%) of 261 in the paracetamol plus ibuprofen group. In adults undergoing total hip arthroplasty, a combination of paracetamol, ibuprofen, and dexamethasone had the lowest morphine consumption within 24 h following surgery and the most favourable adverse event profile, with a lower incidence of serious and non-serious adverse events (primarily driven by differences in nausea, vomiting, and dizziness) compared with paracetamol plus ibuprofen. The Novo Nordisk Foundation and Næstved-Slagelse-Ringsted Hospitals' Research Fund.

Analgesic Self-medication Among Patients With Chronic Musculoskeletal Pain in a South African Chiropractic Teaching Clinic: A Cross-sectional Study

ObjectivesThe purpose of this study was to identify the prevalence of chronic musculoskeletal pain (CMSP) and analgesic self-medication. The knowledge and practices of those who self-medicate with analgesics and factors influencing this was also ascertained. MethodsThis study was a quantitative, descriptive cross-sectional study. A survey was conducted amongst 302 participants with musculoskeletal pain (MSP) attending a chiropractic clinic within a South African tertiary university from July to September 2022. The analysis of analgesic self-medication was limited to participants who reported having CMSP. Data were analyzed using appropriate statistical software and methods, utilizing Chi-square, and nonparametric tests. ResultsThere was a high prevalence of analgesic self-medication with 80% of respondents reporting self-medicating with analgesics to manage their CMSP, and a point prevalence of 57%. More females (86%) than males (69%) self-medicated with analgesics. Participants between 35 and 44 years were statistically more likely to self-medicate with analgesics (P = .048). The majority (96%) sourced their analgesics from a pharmacy without a prescription. It was found that the most frequently used analgesics were nonsteroidal anti-inflammatory drugs (NSAIDS) (70%) followed by paracetamol (58%) and combination analgesics (54%). A significant number of participants (55%) utilizing public health care services used combination analgesics obtained without a prescription compared to 34% of analgesic users that utilized private health care (P < .030). ConclusionThis study showed a high prevalence of self-medication with analgesics, particularly NSAIDs and paracetamol, in participants with CMSP. These findings can guide chiropractors in patient education, reducing self-medication risks and complications.

The role of caffeine in headache disorders.

Caffeine is known to have both beneficial and adverse effects in individuals with headache disorders. This review describes recent findings regarding caffeine that are relevant to headache disorders and puts these findings into the context of clinical management. Preclinical studies show that caffeine has complex effects on sleep, brain blood flow, and intracranial pressure that may depend on the timing of caffeine intake relative to the sleep-wake cycle. Caffeine metabolism may have significant inter-individual variation that influences its therapeutic and/or adverse effects. Caffeine has acute therapeutic benefit for some primary headache disorders. For migraine, this benefit is predominantly in milder headache without cutaneous allodynia. High levels of caffeine intake may contribute to progression of headache disorders. Caffeine-containing combination analgesics commonly cause medication overuse headache. Abrupt reduction in caffeine consumption is a trigger for migraine that may be important in situations including the hospital setting, religious and cultural fasting, and pregnancy. There is not sufficient evidence to support universal guidelines for the use of dietary and medicinal caffeine in headache disorders. A sensible approach based upon available evidence is to limit dietary caffeine intake to moderate amounts with consistent timing before noon, and to use caffeine-containing combination analgesics infrequently for milder headache.

Health care resource utilization and costs associated with diagnosed medication overuse headache and potential acute medication overuse in individuals with migraine.

Estimate health care resource utilization and costs associated with medication overuse headache and potential acute medication overuse. A retrospective analysis was conducted with Clinformatics Data Mart data (1 January 2019-31 December 2019) that included continuously enrolled commercially insured adults with migraine (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code G43.xxx). Medication overuse headache was defined as ≥1 inpatient or ≥2 outpatient claims with an ICD-10-CM code G44.41/40 (drug-induced headache). Potential acute medication overuse was defined as possessing sufficient medication for >10 mean treatment days/month for ergots, triptans, opioids, or combination analgesics or >15 mean cumulative days/month for simple prescription analgesics (e.g., acetaminophen, aspirin, other non-opioid analgesics) for >6 consecutive months. All-cause and migraine-related health care resource utilization and costs were compared after adjusting for demographic and clinical characteristics. Among 90,017 individuals with migraine, the frequency of medication overuse headache/potential acute medication overuse was 12.6% (diagnosed medication overuse headache: 0.6%; potential acute medication overuse: 12.1%). Adjusted all-cause total costs ($31,235 vs $21,486; difference: $9,749 [P < 0.001]) and adjusted migraine-related total costs ($9,770 vs $6,207; difference: $3,563 [P < 0.001]) were higher in the medication overuse headache/potential acute medication overuse group versus those without medication overuse headache/potential acute medication overuse. Individuals with diagnosed medication overuse headache/potential acute medication overuse had higher all-cause and migraine-related health care resource utilization and costs versus individuals without medication overuse headache/potential acute medication overuse, suggesting that improved migraine management is needed to reduce associated costs.

MULTIMODAL POSTOPERATIVE ANALGESIA: COMBINATIONS OF ANALGESICS AFTER ABDOMINAL SURGERY AT CHU- JRA ANTANANARIVO

Introduction :Intense to severe postoperative pain persists despite routine postoperative analgesia. The objective of the study was to determine a type of analgesic combination proposed in the multimodal technique to properly manage postoperative pain after abdominal surgery by laparotomy. Method : A single-center prospective observational study over a period of six months was conducted. Pain scores during the first six hours were assessed during the patients follow-up period. Comparison and correlation tests were used for data analysis (XLSTAT ® v18). Results : The study included 40 patients, aged 46 [18- 71] years, predominatlydemale (68%). Twelve types of surgical intervention were fond for an average duration of 127 [60- 300] minutes. Seven analgesic molecular combinations were used, always including paracetamol. Moderate to severe pain appeared from the second postoperative hour for patients receiving Association 7 while postoperative analgesia lasted until the sixth postoperative hour for those receiving Association 1 . No patient treated by Association 1, 3 and 4 expressed a need for morphine. This demand was high among those under Association 7 . Conclusion : The number and type of analgesics that made up the combination did not have much influence on postoperative pain. The synergism of action of analgesic combinations determines their effect on reducing the postoperative pain thershold for a given surgical procedure of the same type.

Rationale for the topical use of a combination of diphenhydramine hydrochloride and lidocaine hydrochloride in the symptomatic treatment of histamine-dependent allergic and inflammatory skin reactions, accompanied by pruritus.

Allergic reactions caused by external factors are treated with medicinal products containing antihistamines, therefore their action is delayed in time. Combination of antihistamines and fast-acting analgesics may help to reduce discomfort associated with cutaneous reactions. To evaluate efficacy and safety of the combination topical gel containing diphenhydramine hydrochloride 20 mg/g and lidocaine hydrochloride 10 mg/g over placebo in the treatment of local skin inflammatory and allergic reactions. A study was a single-centre, single-dose, randomized, double-blind, two-treatment, two-period, two-sequence cross-over clinical trial (n = 44) in healthy subjects. Local skin inflammatory and allergic lesions were induced by the provocative test with histamine in healthy subjects. For all parameters recorded with the Visual Analogue Scale (VAS), the area under the curve (AUC) was calculated and the peak itch intensity was noted for every subject in response to the skin prick test. The primary endpoint of the study was the difference in AUC calculated from the intensity of itch for test product A (diphenhydramine hydrochloride 20 mg/g and lidocaine hydrochloride 10 mg/g, gel) and placebo product B. The results revealed that itching intensity AUC was significantly greater for product B than for product A, on average by 2.05 points. A decrease in itching intensity was observed from the second minute after application of the test product. The study provided evidence for differences in efficacy between the product tested and placebo.

Study on safety and efficacy of tablet thiocolchicoside 4 mg + tablet aceclofenac 100 mg versus tablet aceclofenac 100 mg + tablet paracetamol 500 mg in treatment of patients with acute lower back pain: A randomized double-blind comparative study

Background: Lower backache is a highly prevalent condition among middle-aged individuals and is often caused by muscle spasms. It is one of the most common reasons why people seek medical assistance from a primary care physician. Aims and Objectives: The aims and objectives of the study are to evaluate the safety and efficacy of the drug combinations thiocolchicoside 4 mg and aceclofenac 100 mg versus aceclofenac 100 mg and paracetamol 500 mg. Materials and Methods: The study was conducted using a prospective, randomized, double-blind, comparative, and parallel group design. A total of 80 patients who met the specified criteria were selected to participate in the trial over a period of 3 months. A total of 30 cases were selected for each group, with consideration given to excluding outliers. The patients were allocated randomly into two groups: Group A, consisting of 30 individuals, and Group B, consisting of 30 individuals. The primary efficacy assessments include the visual analog scale, muscle spasm assessment by finger-to-floor distance, and Lasegue’s maneuver. The secondary efficacy measures were assessed using a 4-point scale global assessment, which included ratings of excellent, good, average, and poor. Results: The majority of study participants were in the age group 39–48 years and above 48 years consisting of 25 patients and 33, respectively. Males constituted 51.6% and females were 48.3%. On day 28, results were calculated on 26 patients in Group A and 24 patients in Group B as 10 patients discontinued the treatment after 3rd week. Conclusions: It is concluded that the best possible medical intervention to treat acute low back pain is to use drug combinations of analgesics and skeletal muscle relaxants. The combination of tablet thiocolchicoside and aceclofenac proved to be more efficacious and safer when compared to the combination of tablet aceclofenac and paracetamol.

THE INFLUENCE OF THE TYPE OF ANESTHESIA ON EARLY POSTOPERATIVE RECOVERY IN PATIENTS WITH ABDOMINAL WALL HERNIAS

Introduction. Pathways to improved recovery after surgery are aimed at reducing surgical stress, maintaining physiologic homeostasis and returning to the patient's baseline functional level prior to surgery.A significant number of patients are operated on each year for hernias of the abdominal wall. One of the unwanted frequent complications is chronic postoperative pain. It can begin as an acute postoperative pain that is difficult to control, the provoking factor can be opioid hyperalgesia. A multimodal analgesia strategy involves combinations of analgesics to achieve clinically necessary analgesia while minimizing significant side effects and reduces dependence of any drug and is an important component of enhanced recovery after surgery (ERAS) protocols.&#x0D; Goal. To assess the efficiency of the types of anesthesia regarding postoperative analgesia and the speed of recovery from the standpoint of patient safety.&#x0D; Materials and methods. 66 patients who underwent surgical treatment of abdominal wall hernias took part in the study. They were divided into 3 groups according to the type of anesthesia (general, neuraxial and fascial blockades of the abdominal wall). Analyzed according to the risk of anesthesia. At different stages of the perioperative period, the use of analgesics was analyzed, the speed of awakening and the intensity of pain according to the VAS scale on the first day were assessed.&#x0D; Results and discussion. The number of patients with the risk of ASA II was greater in the first group (general anesthesia), with the risk of ASA III in the second and third groups (neuraxial anesthesia and fascial blocks), which to some extent affected the choice of the type of anesthesia. According to the Aldrete awakening scale, after the operation, the patients of group 3 had the highest score, respectively, and the shortest time of transfer to the postoperative ward. 42% of patients in group 1 and all patients in group 2 received postoperative analgesia with the use of narcotic analgesics once. Patients in group 3 did not receive narcotic analgesics for postoperative analgesia.&#x0D; Conclusions. The choice of anesthesia method is important to achieve effective results of rapid recovery. Neuraxial and fascial blocks promote faster recovery and allow to reduce or avoid the use of opioid analgesics during surgery. Fascial blocks of the abdominal wall provide long-term and adequate analgesia in the first day of the postoperative period after hernioplasty of the abdominal wall.