Management Of Severe Pain Research Articles

Mirogabalin treatment of postoperative neuropathic pain after thoracic surgery: study protocol for a multicenter, randomized, open-label, parallel-group, interventional trial.

BackgroundIntercostal nerve damage due to thoracotomy or thoracoscopic manipulation is a major contributor to chronic postsurgical pain after pulmonary resection. Chronic postsurgical pain may last for months or years and can negatively impair physical functioning and daily activities. Global consensus on severe postoperative pain management is lacking, and chronic pain incidence after thoracic surgery remains high. Many patients report neuropathic pain, which can be difficult to treat with currently available therapies. The efficacy and safety of mirogabalin have been demonstrated for other types of neuropathic pain; thus, this study was planned to investigate the efficacy and safety of mirogabalin to treat neuropathic pain after thoracic surgery.MethodsIn this multicenter, randomized, open-label, parallel-group, interventional study, patients who are diagnosed with neuropathic pain following removal of a chest drain after lung resection will receive conventional therapy (non-steroidal anti-inflammatory drugs and/or acetaminophen) with or without the addition of a clinical dose of mirogabalin for 8 weeks. For patient stratification, a visual analog scale pain intensity score at baseline of <60 vs. ≥60 mm will be used. Treatment efficacy and safety with and without the addition of mirogabalin will be assessed using a questionnaire evaluating postoperative changes in pain severity and activity. The primary study endpoint is the change in pain intensity from baseline to Week 8, measured by the visual analog scale. Additionally, the presence of chronic pain at 12 weeks after enrollment in each treatment group will be recorded.DiscussionThis protocol has been reviewed and approved by the Clinical Research Review Board of Nagasaki University. Study data will be published in the Japan Registry of Clinical Trials database and peer-reviewed journals. Mirogabalin is already approved for the treatment of other types of neuropathic pain. It is anticipated that this study will provide data to elucidate the impact of mirogabalin treatment, in combination with conventional therapy, to benefit patients with neuropathic pain following thoracic surgery.Trial RegistrationJapan Registry of Clinical Trials Identifier: jRCTs071200053.

CURRENT CONCEPTS IN ANAESTHESIAAND ANALGESIA FOR SHOULDER SURGERY

Shoulder surgery varies from simple diagnostic arthroscopy to major total shoulder arthroplasty. Patients present for shoulder surgery may be young and t with a sports injury or elderly sick with rheumatoid arthritis need arthroplasty of the shoulder joint. Choice of anaesthesia based on the type of surgery, and the comorbidity of a patient. Management of severe postoperative pain is a major challenge for the anaesthesiologist. Regional anaesthetic techniques effectively control static as well as dynamic pain and facilitate early mobilization. However regional blocks are not free from the side effects or complications

Does pain severity predict stone characteristics or outcomes in emergency department patients with acute renal colic?

After initial emergency department (ED) management of acute renal colic, recurrent or ongoing severe pain is the usual pathway to ED revisits, hospitalizations and rescue interventions. If index visit pain severity is associated with stone size or with subsequent failure of conservative management, then it might be useful in identifying patients who would benefit from early definitive imaging or intervention. Our objectives were to determine whether pain severity correlates with stone size, and to evaluate its utility in predicting important outcomes. We used administrative data and structured chart review to study all ED patients with CT proven renal colic at six hospitals in two cities over one-year. Triage nurses recorded arrival numeric rating scale (NRS) pain scores. We excluded patients with missing pain assessments and stratified eligible patients into severe (NRS 8-10) and less-severe pain groups. Stone parameters were abstracted from imaging reports, while hospitalizations and interventions were identified in hospital databases. We determined the classification accuracy of pain severity for stones >5mm and used multivariable regression to determine the association of pain severity with 60-day treatment failure, defined by hospitalization or rescue intervention. We studied 2206 patients, 68% male, with a mean age of 49 years. Severe pain was 52.0% sensitive and 45.3% specific for larger stones >5mm. After multivariable adjustment, we found a weak negative association (adjusted OR =0.96) between pain severity and stone width. For each unit of increasing pain, the odds of a larger stone fell by 4%. Index visit pain severity was not associated with the need for hospitalization or rescue intervention within 60-days. Pain severity is not helpful in predicting stone size or renal colic outcomes. More severe pain does not indicate a larger stone or a worse prognosis.

The Effectiveness of Ketamine Compared to Opioid Analgesics for Management of Acute Pain in Children in the Emergency Department: Systematic Review

Background: Ketamine is increasingly being used as an alternative to opioids in the management of acute pain in the emergency department. In turn, there is increasing research attention to prove the efficacy of ketamine as an analgesic in children presenting in the emergency department. Objective: The first objective of this systematic review was to investigate the effectiveness of ketamine compared to opioid analgesics for pain management in children aged two months to 18 years who have acute pain in the emergency department. The second objective was to compare the adverse events and side effects associated with ketamine with those associated with opioids used for pain management. Methods: A systematic review, using the JBI systematic review was completed. A computerised search from five databases; CINAHL, EMBASE, EMCARE and PubMed, and Cochrane. The included studies were appraised by JBI critical appraisal tool for randomised controlled trials and the study results analysed. Findings: Four randomised control trial studies were included in this systematic review. All the included studies compared ketamine with opioids (morphine and fentanyl) for the management of severe pain in children. The studies were of high methodological quality based on JBI critical appraisal outcome. Meta-analysis was not possible because of the heterogeneity of the studies, especially in terms of different outcome measures, and the approaches (pain assessment tool) used to measure the pain outcomes. The review identified that ketamine demonstrated a non-inferior analgesia effect compared to opioid medication (morphine or fentanyl) as determined by various pain scores used in different studies. However, ketamine use was associated with increased frequency of occurrence of temporary adverse effects that do not require clinical attention. Conclusion: Based on the findings from the review, ketamine is a suitable alternative for opioid analgesics for the management of acute and severe pain in children in ED. The minor transient side effects associated with ketamine should not limit the use of ketamine. Future studies should investigate the appropriate dosage and route of administration of ketamine to be used while managing pain among children with acute and severe pain in the emergency department.

Combined Paresthesia and Subperception Spinal Cord Stimulator Therapy for Management of Persistent Pain After Spinal Fusion Surgery for Congenital Scoliosis

Background: A significant number of patients who undergo spinal fusion surgery are managed in chronic pain clinics for low back pain or what is commonly described as failed back surgery syndrome (FBSS). There are a multitude of reasons for chronic long standing back pain after surgery, and the etiology is often multifactorial involving both preoperative and postoperative risk factors. In patients with scoliosis, it has been shown that fusion with Harrington rods extending into the lumbar region is associated with increases in postoperative back pain, especially with fusions to the L4-L5 region. Spinal cord stimulation (SCS) is a recognized treatment for this condition after repeat surgery or when conservative treatments have failed. Case Report: This case report describes the use of SCS with combination therapy in the management of severe low back pain after thoracolumbar fusion with Harrington rods in a patient with congenital scoliosis. After a failed trial of conservative medical management, a spinal cord stimulator capable of delivering combination traditional paresthesia with subperception and burst stimulation was placed. Regarding the choice of SCS therapy, there is a vast array of choices including traditional paresthesia, paresthesia-free, subperception, microburst, or combination treatment. The latter is capable of delivering multiple therapies over time designed to provide more thorough and longer-lasting relief. Conclusion: Simultaneous traditional paresthesia and subperception waveform therapy might offer superior pain relief in comparison to therapies utilizing a sing=le waveform. Further studies are needed to evaluate the use of combination over traditional SCS therapy for the treatment of axial back pain secondary to FBSS. Key words: Chronic pain, combination therapy, congenital scoliosis, neuromodulation, spinal cord stimulator, spinal fusion

Novel Positive Allosteric Modulators of µ Opioid Receptor-Insight from In Silico and In Vivo Studies.

Opioids are the drugs of choice in severe pain management. Unfortunately, their use involves serious, potentially lethal side effects. Therefore, efforts in opioid drug design turn toward safer and more effective mechanisms, including allosteric modulation. In this study, molecular dynamics simulations in silico and ‘writhing’ tests in vivo were used to characterize potential allosteric mechanism of two previously reported compounds. The results suggest that investigated compounds bind to μ opioid receptor in an allosteric site, augmenting action of morphine at subeffective doses, and exerting antinociceptive effect alone at higher doses. Detailed analysis of in silico calculations suggests that first of the compounds behaves more like allosteric agonist, while the second compound acts mainly as a positive allosteric modulator.

Rapid Administration of Methoxyflurane to Patients in the Emergency Department (RAMPED) Study: A Randomized Controlled Trial of Methoxyflurane Versus Standard Care.

The objective was to evaluate the effectiveness of methoxyflurane versus standard care for the initial management of severe pain among adult emergency department (ED) patients. This randomized parallel-group open-label phase IV trial of methoxyflurane was conducted in a tertiary hospital ED setting in Australia. Inclusion criteria required adult patients to have an initial pain score≥8 on the 11-point Numerical Rating Scale (NRS). Patients were randomized 1:1 to receive either inhaled methoxyflurane (3mL) or standard analgesic treatment at ED triage. The primary outcome was the proportion of patients achieving clinically substantial pain reduction, defined as a≥50% drop in the pain score at 30minutes. Secondary outcomes included the pain score at multiple time points (15, 30, 60, 90minutes) and the difference in the proportion of patients achieving a >2-point reduction on the NRS. There were 120 patients randomized and analyzed between September 4, 2019, and January 16, 2020. The primary outcome was achieved in six (10%) patients in the methoxyflurane arm and three (5%) in the standard care arm (p=0.49). A higher proportion of patients in the methoxyflurane arm reported a >2-point drop on the NRS at all time points (17% vs. 5% at 15minutes, 25% vs. 9% at 30minutes, 30% vs. 10% at 60minutes, and 33% vs. 13% at 90minutes). Methoxyflurane use was also associated with lower median pain scores at all time points. Initial management with inhaled methoxyflurane in the ED did not achieve the prespecified substantial reduction in pain, but was associated with clinically significant lower pain scores compared to standard therapy.

Safe Use of Opioids in Chronic Kidney Disease and Hemodialysis Patients: Tips and Tricks for Non-Pain Specialists.

In patients suffering from moderate-to-severe chronic kidney disease (CKD) or end-stage renal disease (ESRD), subjected to hemodialysis (HD), pain is very common, but often underestimated. Opioids are still the mainstay of severe chronic pain management; however, their prescription in CKD and HD patients is still significantly low and pain is often under-treated. Altered pharmacokinetics and the lack of clinical trials on the use of opioids in patients with renal impairment increase physicians’ concerns in this specific population. This narrative review focused on the correct and safe use of opioids in patients with CKD and HD. Morphine and codeine are not recommended, because the accumulation of their metabolites may cause neurotoxic symptoms. Oxycodone and hydromorphone can be safely used, but adequate dosage adjustments are required in CKD. In dialyzed patients, these opioids should be considered as second-line agents and patients should be carefully monitored. According to different studies, buprenorphine and fentanyl could be considered first-line opioids in the management of pain in CKD; however, fentanyl is not appropriate in patients undergoing HD. Tapentadol does not need dosage adjustment in mild-to-moderate renal impairment conditions; however, no data are available on its use in ESRD. Opioid-related side effects may be exacerbated by common comorbidities in CKD patients. Opioid-induced constipation can be managed with peripherally-acting-μ-opioid-receptor-antagonists (PAMORA). Unlike the other PAMORA, naldemedine does not require any dose adjustment in CKD and HD patients. Accurate pain diagnosis, opioid titration and tailoring are mandatory to minimize the risks and to improve the outcome of the analgesic therapy.

Comparison of Ketamine and Tramadol in Management of Acute Pain; a Systematic Review.

Management of pain is an important part of care in the emergency department (ED). Tramadol and Ketamine have both been introduced as alternatives to opioids in the ED and post-operative setting. In this study, we conducted a systematic review of available literature to compare the analgesic efficacy, and side effect profile of these two medications in management of severe acute pain. This is a systematic review based on the PRISMA protocol. In this study, peer-reviewed papers published by March 3, 2020, which compared analgesic effects of tramadol and ketamine in management of acute pain were included. The initial search of online databases identified 2826 non-duplicate records. Finally, three papers available in full text were analyzed for study quality. The results show that ketamine has consistently been shown to be superior to tramadol for pain control and causes fewer significant side effects. Results of this review show that low-dose ketamine is more effective than tramadol in pain control, while causing fewer side effects.

Pain Reduction Emergency Protocol: A Prospective Study Evaluating Impact of a Nurse-initiated Protocol on Pain Management and Parental Satisfaction.

Pain control remains suboptimal in pediatric emergency departments (EDs). Only 60% of pediatric patients requiring pain medications receive them in the ED, with an average time of administration being 90 minutes after arrival. Although pain protocols (PP) have been proposed and evaluated in children with long-bone fractures, data on PP utility for general pediatric patients with acute pain are limited. Our objective is to introduce a nursing-initiated PP with medication algorithms for use in triage, measure the improvement in management of severe pain on arrival to the ED and determine the effect on parental satisfaction. Prospective prestudy and poststudy conducted from June to October 2017. Patients aged 3 to 17 years presenting to a large tertiary pediatric ED with acute pain were eligible. Preprotocol demographics, clinical data, and pain interventions were obtained over a 6-week period. A convenience sample of parents completed a satisfaction survey rating their experience with ED pain management during this time. In the 4-week intervention phase, the PP was introduced to our ED nurses. Postintervention data were collected in the same fashion as the preintervention phase. Analysis was done using independent sample t test and χ2 models. There were 1590 patients evaluated: preprotocol (n = 816), postprotocol (n = 774). Approximately 10% more patients with severe pain received pain medication in the post-PP sample compared with pre-PP (85.6% and 75.9% respectively). Parental satisfaction was higher in patients who received analgesic medications within 90 minutes of arrival to the ED (P = 0.007). The introduction of a PP in the ED setting improved the treatment of pain. There was a significant increase in patients with severe pain receiving analgesic medications. Additionally, parents were more satisfied if their children received pain medication in a more timely fashion. Pediatric EDs should consider introducing PPs to improve appropriate and timely administration of pain medication in triage.

CT-guided Celiac Plexus Neurolysis in the Management of Severe Upper Abdominal Pain

CT-guided Celiac Plexus Neurolysis in the Management of Severe Upper Abdominal Pain

An up-to-date overview of sublingual sufentanil for the treatment of moderate to severe pain

ABSTRACT Introduction Sufentanil is a selective µ-opioid agonist, used intravenously and intrathecally for moderate to severe acute pain. Sublingual sufentanil nanotablets have been developed; 15 mcg tablet for a patient-controlled analgesia device and 30-mcg tablet for a single-dose device administered by a healthcare professional. Dosing interval is a minimum of 20 min for a 15 mcg tablet and a treatment duration of up to 72 hours. The single 30-mcg nanotablet dosing interval is 1 hour. Mean plasma elimination half-life is 13 hours and bioavailability 47–57% after the first sublingual sufentanil tablet. Areas covered This review focuses on the effectiveness, safety, and feasibility of sublingual sufentanil 30-mcg single dose suspended by a healthcare professional for the management of moderate to severe acute pain. A few Phase 4 studies concerning the sublingual sufentanil tablet system containing 15-mcg nanotablets are also reviewed. Expert opinion Sufentanil sublingual 30-mcg nanotablets provide effective pain relief in various acute moderate to severe pain states. The safety profile of sublingual sufentanil 30 mcg is typical to opioids nausea, vomiting, and sedation being the most common ones. Sublingual sufentanil 30-mcg nanotablet has the potential for efficient moderate to severe pain management in supervised healthcare facilities.

Antagonism of peripheral opioid receptors by methylnaltrexone does not prevent morphine tolerance in rats.

Opioids are effective analgesics in the management of severe pain. However, tolerance, leading to dose escalation and adverse effects are significant limiting factors in their use. The role of peripheral opioid receptors in analgesia has been discussed especially under inflammatory conditions. The results from pharmacological and conditional knockout studies together do not provide a clear picture of the contribution of peripheral opioid receptors on antinociceptive tolerance and this needs to be evaluated. Therefore, we studied whether the peripherally restricted opioid receptor antagonist, methylnaltrexone (MNTX), could prevent morphine tolerance without attenuating the antinociceptive effect of morphine. Male Sprague-Dawley rats were treated for 7days with increasing subcutaneous doses of morphine (5-30mg/kg) and were coadministered saline, MNTX (0.5 or 2mg/kg), or naltrexone (NTX; 2mg/kg). Nociception was assessed with tail-flick, hotplate, and von Frey tests. Morphine, MNTX, and NTX concentrations in the plasma, brain, and spinal cord were measured by liquid chromatography-tandem mass spectrometry. In acute coadministration, NTX, but not MNTX, abolished the acute antinociceptive effects of morphine in all nociceptive tests. The antinociceptive tolerance after repeated morphine administration was also prevented by NTX but not by MNTX. MNTX penetrated to the spinal cord and the brain to some extent after repeated administration. The results do not support the use of MNTX for preventing opioid tolerance and also suggest that morphine tolerance is mediated by central rather than peripheral opioid receptors in the rat.

Self-Emulsifying Drug Delivery System of Celecoxib for Avoiding Delayed Oral Absorption in Rats with Impaired Gastric Motility.

This study aimed to develop a self-emulsifying drug delivery system (SEDDS) of celecoxib (CEL) for suppressed delay in oral absorption under impaired gastric motility. A pseudo-ternary phase diagram was constructed for the determination of the optimal component ratio in SEDDS of CEL (SEDDS/CEL), and the SEDDS/CEL was physicochemically characterized. A pharmacokinetic study on orally dosed CEL samples (5-mg CEL/kg) was carried out in normal and propantheline (PPT)-treated rats to mimic impaired gastric motility. SEDDS/CEL rapidly formed a fine emulsion with a mean size of 147nm in distilled water and significantly improved the dissolution behavior of CEL under pH 1.2 condition with a 20-fold higher dissolved amount than crystalline CEL. In normal rats, orally dosed SEDDS/CEL provided a 4.6-fold higher systemic exposure than that of crystalline CEL, due to the improved dissolution properties of CEL. Crystalline CEL showed delayed and decreased oral absorption of CEL in PPT-treated rats as evidenced by a 6.9-h-delayed mean absorption time and only 12% of the systemic exposure of CEL compared with those in normal rats. In contrast, SEDDS/CEL enhanced the oral absorption of CEL with a 14.6-fold higher systemic exposure with significant suppression of delay in absorption than crystalline CEL even in PPT-treated rats. SEDDS/CEL could be an efficacious option for suppressing delay in CEL absorption even under impairment of gastric motility, possibly leading to rapid and reproducible management of severe acute pain.

Management of Severe Pain in Terminally Ill Patients at Home: An Evidence-Based Strategy.

The purpose of this article is to describe current evidence-based strategies to manage severe pain in patients living with terminal illnesses. A comprehensive pain assessment is a critical step in the initial development of a pain management plan and for ongoing evaluation of patients' pain. Although we have many effective clinical tools available for pain assessment, they are not always used consistently, which can negatively affect the pain management plan. Home care and hospice nurses need to be consistent in using the tools and documenting the patient's pain level and response to the pain management plan. Patients and caregivers have concerns and fears surrounding medication use, particularly with narcotic analgesics. It is vital that nurses provide thorough patient-centered teaching about medications to help address these concerns. Research has found that nurses who also provided validation to patients and families regarding their concerns, followed by education, were the most effective.

Management of Severe Pain in Terminally Ill Patients at Home

Management of Severe Pain in Terminally Ill Patients at Home

Stability Testing of Compounding Capsule Combination between Paracetamol and Tramadol in a Private Hospital Semarang

A combination of Paracetamol and Tramadol is used in mild to severe pain management. In a private Hospital Semarang, this combination is included in fast-moving drugs that it is frequently compounded and prepared in advance. The study aims t o determine Beyond Use Date (BUD) in compounding capsules combination between Paracetamol and Tramadol samples. Beyond Use Date is a time limit indicating that a medicine beyond the expiration date must not be used and determined based on the results of stability testing. Samples were stored for 14 days in a tightly closed container far from direct sunlight in room temperature without AC (28 0 C) and without silica gel, room temperature with AC (25 0 C) without silica gel, and room temperature with AC (25 0 C) with silica gel. Furthermore, samples underwent physical and chemical stability testing. Physical stability testing was conducted using organoleptic testing by observing direct changes from the powder color in capsules, capsules form, and scent on the samples. Meanwhile, chemical stability testing was conducted by determining the content of active ingredient from the samples using reversed-phase HPLC method and C18 as the stationary phase, methanol and aquabidest (40:60) as the mobile phase, wavelength 271 nm, flow rate 0.6 mL/min and injection volume 10 μL. The result shows that s amples were physically stable for being able to retain the original physical properties showed by consistent powder color and capsules form, and there was no available scent. However, the chemical stability testing method was unable to separate and quantify the content of Paracetamol, Tramadol, and formed degradation products. It can be concluded that Beyond Use Date based on organoleptic and chemical stability testing for 14 days of compounding capsules combination between Paracetamol and Tramadol could not be determined. Nevertheless, this study showed favorable storage conditions in a tightly closed container far from direct sunlight in Room Temperature with AC (25 0 C) with Silica Gel.

Intrathecal opioids: equally efficacious at any age.

Intrathecal opioid pumps have been used in the management of severe chronic pain for more than 40years. Numerous studies have shown significant therapeutic effects alongside tolerable side effects. In the last decades, life expectancy has increased in many countries in the world. With an aging population, the question arises whether effects equal to those in younger patients can also be achieved in elderly patients. This study is an in-depth re-analysis of data published previously. 36 patients were analyzed. The sample included 18 elderly patients (> 65years) and 18 younger patients. No differences between the two samples were found with regard to pain intensity under intrathecal opioid therapy and prior to implantation of the opioid pump. Likewise, there were no differences in anxiety/depression scores and pain-related disability. Side effects were reported at similar rates by the elderly patients and by the younger patients. Elderly patients showed a tendency towards lower opioid doses and slower dose increases. Our data hint at a consistent efficacy of intrathecal opioid therapy in elderly patients even after long-term treatment. Side effects of the treatment are relatively frequent but mild and no side effects were particularly frequent in elderly people.

Analyzing and Benchmarking Global Consumption Statistics for Opioid Analgesics 2015: Inequality Continues to Increase

Many countries around the world have a very low per capita consumption of opioid analgesics, which is probably related to absence or inadequate management of moderate and severe pain for large parts of their populations. We conducted a longitudinal observational study with opioid analgesic consumption data for all countries from 2000–2015, to assess 2015 per capita consumption data for strong opioid analgesics and to investigate the hypothesis that inequality decreased over the years 2000–2015. We based our study on the official statistics kept by the International Narcotics Control Board, built on data submitted by governments annually. Adequate consumption was defined as the average 2015 opioid analgesic consumption of the 20 most-developed countries, or above. In addition, we defined categories of moderate, low, very low and extremely low consumption, each category differing 0.5 on a logarithmic scale. Consumption was expressed as the AOC Index. The direction of inequality in consumption between different countries’ development levels through the years 2000–2015 was assessed using a mixed effects model. We found that the average consumption of the 20 most-developed countries was 256 ± 208 mg per capita (range 5.9–778) in 2015. In all, 119 countries did not have a moderate or adequate consumption of opioid analgesics. Inequality of adequacy of consumption between low- and highly-developed countries increased from 2000 to 2015. The world needs 1867 tonnes ME for treating pain with opioids analgesics at an adequate level (actual use: 365 tonnes or 19.5% of the global need). We concluded that in 2015, almost 6.5 billion people lived in countries where opioid analgesic consumption was low, very low, or extremely low.

Randomized Controlled Trial of a Natural Food-Based Fiber Solution to Prevent Constipation in Postoperative Spine Fusion Patients.

Constipation after orthopaedic surgery occurs frequently, likely due to a combination of high levels of opioid medications for severe pain management and mobility limitations after surgery. It can result in serious complications, increased cost, and patient discomfort. This study evaluated a natural food-based fiber solution to prevent constipation in postoperative orthopaedic patients. A posttest control group-randomized study design was used. Dependent variables were presence of postoperative constipation, time to first bowel movement (BM), and total number of postoperative BMs. Descriptive statistics, Student's t tests, and Mann-Whitney nonparametric 2-group tests with chi-square analysis were used. Level of significance for all tests was p < .05. Forty-six participants were evaluated. Ages were similar for both the intervention and control groups. Bowel Function Index (BFI) scores were not significantly different (p = .448). No significant group differences were present for the individual BFI item scores (p > .05). The number of patients with a BM during the first 3 days was not significantly different (p = .489). There were no significant differences found between the 2 groups regarding laxative administration (p > .05 for all laxatives). Further studies are indicated that address natural fibers and pharmaceutical methods for the prevention of constipation after spinal surgery.