Pain Management Strategies in Intensive Care Unit: Challenges and Best Practice.

Pain management in the ICU (intensive care unit) is a very complex problem which involves a wide variety of conditions, lack of sufficient tools for use, and high personnel to patient ratio. In the last three decades, pain as a clinical issue has become well analyzed, and treatment protocols based on scientific evidence have been established. Besides medication, some non-pharmacological methods such as music therapy, relaxation, and massage have been proven to be very much practical and manageable in pain management of ICU. The main opioids are utilized predominantly due to their power but NSAIDs and local anesthesia are combined with opioids with the aim to reduce the pain as much as possible. Yet more research now has to prove that pain evaluation and management is effective. This article discusses on the issues and the best approaches to solving them when managing pain in ICU patients.

Sequential Release of Ibuprofen and the Gasotransmitter Hydrogen sulfide using Oxanorbornane-based Synthetic Lipids as Carriers.

After understanding the biological signaling roles of hydrogen sulfide and its involvement in various physiological processes, there has been enormous interest in exploring its therapeutic utility in areas such as cancer, inflammation, cardiovascular diseases, etc. There is also growing interest in using suitable H2S donors in combination with other drugs to improve the treatment outcome through the modulation of multiple pathways. The premature release of H2S from small molecule donors and the difficulty in controlling its spatio-temporal distribution are the major challenges during these efforts. Hence the development of appropriate carriers that can release this gasotransmitter along with the therapeutic entity of interest in a controlled manner has high significance. In this regard, this report presents a novel drug delivery system from oxanorbornane-based synthetic lipids that carries a H2S-releasing 1,2-dithiole-3-thione moiety as part of the head group. Nanoaggregates of the resulting conjugate are not only capable of efficiently entrapping a non-steroidal anti-inflammatory drug such as ibuprofen, but also release this drug and H2S in a controlled and sequential manner.

Acrocyanosis as a rare presentation of drug-induced cutaneous vasculitis: a case report.

BACKGROUND: Acrocyanosis is characterised by persistent bluish discolouration of the extremities, resulting from reduced peripheral blood flow leading to increased oxygen extraction. The aetiology can be divided into primary and secondary causes. While primary acrocyanosis is generally painless and has a benign course, secondary causes may lead to complications. This case reported acrocyanosis secondary to cutaneous vasculitis which progressed to digital gangrene, which is a rare complication of cutaneous vasculitis. CASE PRESENTATION: A 68-year-old man presented with a four-day history of bluish discolouration involving bilateral toes associated with pain and started to become gangrenous. Investigations for critical limb ischemia did not show evidence of critical arterial stenosis. Further history revealed history of recent administration of intramuscular injections with diclofenac, a non-steroidal anti-inflammatory agent for renal colic pain a few days prior to the onset of the. Thorough skin search showed multiple purpuric rash of his thighs, buttocks and abdomen. Skin biopsy confirmed the diagnosis of cutaneous (lymphocytic) vasculitis, which was likely to be drug-induced. The acrocyanosis initially responded to methylprednisolone, however unfortunately it progressed further to digital gangrene which required bilateral transmetatarsal amputations. CONCLUSION: Knowledge on clinical features, aetiology and investigations of secondary acrocyanosis is crucial for early recognition and treatment of the underlying cause to prevent irreversible complications.

The common cold: The need for an effective treatment amid the FDA discussion on oral phenylephrine.

An episode of the common cold can have a significant negative impact on quality of life, mood, and daily activities. In line with this fact, there is a growing demand for health care and treatments associated with the common cold. Current treatments aim to (1) inhibit symptom severity and (2) shorten the duration of an episode of the common cold. These products include analgesics, antihistamines, and decongestants. In addition, various supplements, including vitamins, minerals, and herbs, are marketed to treat the common cold. The current products marketed for treating the common cold may reduce the severity of some (but not all) common cold symptoms, but they usually do not shorten the common cold episode. The recent indication that phenylephrine is not effective means that it will ultimately need to be removed from the over-the-counter monograph. Manufacturers will consequently need to reformulate their products and withdraw oral phenylephrine-containing products. Several newly developed common cold products are currently under investigation. These clinical trials should evaluate their efficacy and safety, as there remains a clear need for common cold products that significantly reduce both the symptom severity and the duration of episodes of the common cold.

Nonsteroidal anti-inflammatory drug use by patients: Impact of modular educational training on pharmacists' questioning, counselling and risk assessments.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs)-related morbidity and mortality can be reduced through medication counselling and risk reduction. Objectives: This study evaluated the impact of short online modular NSAID training on the type and quality of questions asked, risk factors assessed, and counselling offered by community pharmacists to NSAID users. Methods: A cross-sectional questionnaire-guided survey conducted in Ibadan, Nigeria, among 87 pharmacists evaluated the frequency of counselling, NSAID risk factor assessment and barriers to risk assessment. Additionally, a before-and-after RCT was used to evaluate the impact of short online modular NSAID training for the intervention group (IG) on the type and quality of the questions asked, counselling provided, and risk assessed by the pharmacists. Eight standardised patients, aged 25-43 years, four at pre- and postintervention, presented four standardised scenarios at community pharmacies [IG, n = 22, control group (CG, n = 30)] to assess these outcomes. The quality of each outcome (questions asked, counselling offered and risk assessed) was classified as poor (0-≤20%), fair (>20-≤40%), moderate (>40 - ≤60%), or optimal (>60-100%). The data are presented with descriptive statistics. Results: The community pharmacists reported counselling patients on NSAID precautions (80-86%) and dosages (51-69%). Gastrointestinal bleeding risk was assessed by 61-89% of the pharmacists, and time constraints (39-42%) and patient impatience (47-75%) were some barriers to risk assessment. Online modular educational intervention significantly improved the types and quality of questions asked by pharmacists (CG: poor to fair, 16%-21%; IG: poor to moderate, 14%-45%), NSAID risk factors assessed (CG: poor to poor, 10%-9%; IG: poor to fair, 11%-27%) and counselling offered (CG: poor to poor, 6%-7%; IG: poor to fair, 6%-22%). Conclusions: Short online modular educational training on NSAIDs improved the types and quality of the questions asked, NSAID risk factors assessed, and counselling provided by community pharmacists to patients during consultations.

Development and Validation of a Machine Learning-based, Point-of-Care Risk Calculator for Post-ERCP Pancreatitis and Prophylaxis Selection.

BACKGROUND AND AIMS: A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning-based tool for PEP risk prediction to aid in clinical decision-making related to periprocedural prophylaxis selection and post-procedural monitoring. METHODS: Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a one-month period. RESULTS: A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on twenty PEP risk factors and 5 prophylactic interventions (rectal non-steroidal anti-inflammatory drugs [NSAID], aggressive hydration, combined rectal NSAID and aggressive hydration, pancreatic duct [PD] stenting, and combined rectal NSAID and PD stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74. CONCLUSIONS: This study demonstrates the feasibility and utility of a novel machine learning-based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended post-procedure monitoring.

Diclofenac enhances Boron nitride nanoparticle toxicity in freshwater green microalgae, Scenedesmus obliquus: Elucidating the role of oxidative stress.

Boron nanoparticles have numerous medical, industrial, and environmental applications as potential nanomaterials. Given the inevitable release of these particles in aquatic environments, they can combine with other pollutants like pharmaceuticals. Therefore, it is necessary to investigate their combined detrimental effects on freshwater biota. This study examined the joint impacts of Boron nitride nanoparticles (BNNPs) and Diclofenac (DCF) on freshwater microalgae Scenedesmus obliquus. Three different concentrations of BNNPs (0.1, 1, and 10 mg L-1) were mixed with 1 mg L-1 of DCF and were treated with algal cells, and biochemical analyses were performed. A concentration-dependent decrease in algal cell viability was observed after a 72-h interaction period with BNNPs and their binary combinations. The maximum toxic effects were observed for the highest combination of BNNPs + DCF, i.e., 10 mg L-1 BNNPs + 1 mg L-1 DCF. Similarly, an increase in the oxidative stress parameters and antioxidant enzyme activity was observed, which correlated directly to the decline in cell viability. The algal cells also showed reduced photosynthetic efficiency and electron transfer rate upon interaction with BNNPs. The results of this research emphasize the importance of considering the negative consequences of emerging pollutants and their combinations with other pollutants, BNNPs, and DCF as part of a thorough evaluation of ecotoxicity in freshwater algal species.

A False Alarm of Acute Abdomen: Epiploic Appendagitis Case Report and Literature Review.

An acute abdomen that is tender to palpation often represents a life-threatening emergency requiring immediate surgical or medical management. We present a case of acute abdomen with peritoneal signs and symptoms due to epiploic appendagitis (EA) that resolved with a single dose of ibuprofen. EA often mimics appendicitis, diverticulitis, and rarely cholecystitis based on its location. It arises due to ischemic infarction of an epiploic appendage, typically caused by torsion or spontaneous thrombosis of the central draining vein. Despite its rarity, clinicians need to recognize the characteristic imaging findings of EA on CT and ultrasound to avoid unnecessary surgical interventions and to manage the condition conservatively.

Aspirin hypersensitivity diagnostic index (AHDI): In vitro test for diagnosing of N-ERD based on urinary 15-oxo-ETE and LTE4 excretion.

BACKGROUND: 15-oxo-eicosatetraenoic acid (15-oxo-ETE), is a product of arachidonic acid (AA) metabolism in the 15-lipoxygenase-1 (15-LOX-1) pathway. 15-oxo-ETE was overproduced in the nasal polyps of patients with nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). In this study we investigated the systemic biosynthesis of 15-oxo-ETE and leukotriene E4 (LTE4) and assessed their diagnostic value to identify patients with N-ERD. METHODS: The study included 64 patients with N-ERD, 59 asthmatics who tolerated aspirin well (ATA), and 51 healthy controls. A thorough clinical characteristics of asthmatics included computed tomography of paranasal sinuses. Plasma and urinary 15-oxo-ETE levels, and urinary LTE4 excretion were measured using high-performance liquid chromatography and tandem mass spectrometry. Repeatability and precision of the measurements were tested. RESULTS: Plasma 15-oxo-ETE levels were the highest in N-ERD (p < .001). A receiver operator characteristic (ROC) revealed that 15-oxo-ETE had certain sensitivity (64.06% in plasma, or 88.24% in urine) for N-ERD discrimination, while the specificity was rather limited. Modeling of variables allowed to construct the Aspirin Hypersensitivity Diagnostic Index (AHDI) based on urinary LTE4-to-15-oxo-ETE excretion corrected for sex and the Lund-Mackay score of chronic rhinosinusitis. AHDI outperformed single measurements in discrimination of N-ERD among asthmatics with an area under ROC curve of 0.889, sensitivity of 81.97%, specificity of 87.23%, and accuracy of 86.87%. CONCLUSIONS: We confirmed 15-oxo-ETE as a second to cysteinyl leukotrienes biomarker of N-ERD. An index based on these eicosanoids corrected for sex and Lund-Mackay score has a similar diagnostic value as gold standard oral aspirin challenge in the studied group of patients with asthma.

Protective role of M3 muscarinic acetylcholine receptor in indomethacin-induced small intestinal injury.

EP4 prostanoid receptor (EP4R) contributes to the intestinal epithelial Cl- secretion, and inhibition of prostaglandin E (PGE) production by non-steroidal anti-inflammatory drugs (NSAIDs) plays a central role in NSAID-induced enteropathy. Although M3 muscarinic acetylcholine receptor (M3R) also contributes to the intestinal epithelial Cl- secretion, it remains unclear whether M3R is involved in NSAID-induced enteropathy due to a lack of selective agents. The present study explored how M3R is involved in the regulation of the intestinal epithelial Cl- secretion and its pathophysiological role in NSAID-induced enteropathy. Using the novel highly-selective M3 positive allosteric modulator PAM-369 that we recently developed, we evaluated the role of M3R in the intestinal epithelial secretion ex vivo by measuring the short circuit current (Isc) of intestinal epithelium with a Ussing chamber system and examined whether or not M3R protects against small intestinal injury in indomethacin-treated mice. Both the PGE1 derivative misoprostol and carbachol similarly increased the Isc in a concentration-dependent manner. The Isc increases were abolished either by receptor antagonists (an EP4R antagonist and a M3R antagonist, respectively) or by removal of extracellular Cl-. PAM-369 enhanced the carbachol-induced Isc by potentiating M3R, which could contribute to enhanced intestinal epithelial secretion. Treatment with PAM-369 ameliorated small intestinal injury in indomethacin-treated mice. Importantly, the M3R expression was significantly up-regulated, and PAM-369 potentiation of M3R was augmented in indomethacin-treated mice compared to untreated mice. These findings show that M3R plays a role in maintaining the intestinal epithelial secretion, which could contribute to protection against indomethacin-induced small intestinal injury. M3R is a promising target for treating or preventing NSAID-induced enteropathy. KEY MESSAGES: PAM-369, the M3 positive allosteric modulator, was used to potentiate M3R. PAM-369 enhanced carbachol-induced Isc in mouse ileum. PAM-369 ameliorated small intestinal injury in indomethacin-treated mice. M3R is a promising target for treating or preventing NSAID-induced enteropathy.

Management of NSAID-Induced Penetrating Gastric Ulcer Complicated by Hemorrhagic Cholecystitis: The Role of Percutaneous Transhepatic Biliary Drainage.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for their analgesic and anti-inflammatory effects but can lead to serious gastrointes complications. This report illustrates the management of an NSAID-induced penetrating gastric ulcer with subsequent postoperative hemorrhagic cholecystitis. A 68-year-old female with chronic NSAID use presented with epigastric pain and was diagnosed with a penetrating gastric ulcer extending into the retroperitoneum. The surgical management required a shift from a minimally invasive robotic-assisted approach to an open procedure due to unexpected intraoperative findings. The postoperative period was notable for the development of hemorrhagic cholecystitis that was managed with percutaneous transhepatic biliary drainage, highlighting the role of interventional radiology in complex postoperative care. NSAID use significantly increases gastrointestinal risks, leading to complications such as ulcers that may penetrate into adjacent structures, including the retroperitoneum. The management of penetrating gastric ulcers typically involves complex surgical procedures, highlighted in this scenario by the necessity for an antrectomy followed by a Billroth II reconstruction to address the extensive damage and restore gastrointestinal continuity, which is essential for patient recovery. In this case, the development of hemorrhagic cholecystitis postoperatively was effectively managed with a percutaneous transhepatic biliary drain, demonstrating the importance of interventional radiology in managing postoperative complications and the need for a multidisciplinary approach. This case report elucidates the management of NSAID-induced penetrating gastric ulcer that extended into the retroperitoneum, necessitating an antrectomy with Billroth II reconstruction. A gastric ulcer is generally classified as "large" if it exceeds 2 centimeters in diameter. These ulcers pose greater risks of complications such as perforation, penetration into adjacent organs, bleeding, and obstruction, necessitating more complex and comprehensive management strategies. The postoperative complication of hemorrhagic cholecystitis was effectively managed via interventional radiology, highlighting the critical role of minimally invasive techniques in addressing severe postoperative complications.

Non-Steroidal Anti-Inflammatory Drugs Administered Intra-Articularly in Temporomandibular Joint Disorders: A Systematic Review and Meta-Analysis.

Objectives: This systematic review was designed to summarize randomized controlled trials of intra-articular administration of non-steroidal anti-inflammatory drugs (NSAIDs) for temporomandibular disorders. Methods: Randomized controlled trials regarding intra-articular injections of non-steroidal anti-inflammatory drugs for temporomandibular disorders were included in the review. The final search was conducted on 16 June 2024 in the Bielefeld Academic Search Engine, PubMed, and Scopus databases. Results: Of the 173 identified studies, 6 were eligible for review. In trials comparing arthrocentesis alone to arthrocentesis with NSAIDs, slight differences in joint pain were noted. For tenoxicam, differences were under 1 point on a 0-10 scale after 4 weeks, with inconsistent results. Piroxicam showed no significant difference, and pain levels were minimal in both groups. For maximum mouth opening (MMO), tenoxicam showed no significant difference. Piroxicam increased MMO by nearly 5 mm, based on one small trial with bias concerns. Conclusions: Currently, there is no strong scientific evidence supporting the injection of NSAIDs into the temporomandibular joint to relieve pain or increase jaw movement. Preliminary reports on piroxicam with arthrocentesis and tenoxicam or diclofenac without rinsing justify further research.

Updates on the Natural History and Clinical Characteristics of NSAID-ERD.

Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) is a distinct clinical syndrome characterized by nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity, asthma, and nasal polyposis. Its diagnosis is challenging owing to variable presentations and a lack of simple tests, leading to diagnostic delays. Recent research has revealed its genetic predispositions, environmental triggers, and associations with atopy and second-hand tobacco smoke exposure or smoking cessation. Despite its severity, diagnostic awareness remains low, leading to the delay in effective management. Therapeutically, NSAID-ERD necessitates multidisciplinary approaches, often combining surgical interventions with medical management, including aspirin desensitization and biologic agents. However, predictive biomarkers for treatment response remain elusive. Understanding the underlying mechanisms driving NSAID-ERD pathogenesis and identifying reliable biomarkers are crucial for enhancing diagnostic accuracy and refining targeted therapeutic strategies for this debilitating condition. This review aims to provide a thorough understanding of NSAID-ERD, covering its history, clinical features, epidemiology, diagnosis, systemic and molecular biomarkers, available treatment options, and avenues for future research.

The Burden of Nonsteroidal Anti-Inflammatory Drug-Exacerbated Respiratory Disease: Interplay Between Quality of Life and Economic Implications.

Nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) presents a significant challenge in clinical management owing to recalcitrant disease with accompanying profound impacts on patient quality of life. Although asthma represents a significant component of this disease, quality of life disruptions are driven primarily by recalcitrant sinonasal problems, olfactory dysfunction, and the associated psychosocial and dietary implications. This review delves into specific quality of life metrics used to assess NSAID-ERD and the associated health care burden and financial implications of this disease, offering insights into the comparative challenges in chronic rhinosinusitis with nasal polyps when available. The article reviews the associated costs and cost-effectiveness of NSAID-ERD-directed therapies, including endoscopic sinus surgery, aspirin desensitization, and biologic therapy. Although some of these emerging treatment approaches show promise, they also present numerous unanswered questions, reflecting the dynamic nature of this field. As the landscape of NSAID-ERD management continues to evolve, this review provides insights into the challenges faced by clinicians and underscores the need for further research to optimize patient care and quality of life outcomes.

New Onset of Symptomatic Peptic Ulcer Disease Postpartum Secondary to Nonsteroidal Anti-Inflammatory Drug Use.

The use of nonsteroidal anti-inflammatory drug (NSAID) medications is a risk factor for peptic ulcer disease (PUD). PUD in the postpartum period is rare, despite the common use of NSAIDs. A G1P0 presented 6 days postcesarean section with fatigue, lightheadedness, melenic stools, and a hemoglobin of 5.4 g/dL after using NSAIDs and acetaminophen for postoperative pain control. An esophagogastroduodenoscopy (EGD) was performed for a suspected upper gastrointestinal bleed and found one gastric and one duodenal ulcer. Though typically used for a short course in the postpartum period, NSAIDs remain a predisposing risk factor for PUD postpartum, and patients and providers must be aware of this risk.

Anaphylaxis as an Unusual Cause of Shock in the Trauma Setting: A Case Report.

Anaphylactic shock is the most severe form of an acute systemic allergic reaction and can be potentially lethal if left untreated. Here, we present the case of a 51-year-old male with no significant medical history, who arrived at our hospital's emergency trauma bay following a motor vehicle accident caused by a sudden onset of malaise while driving. Upon arrival, the patient's airway was patent, but he reported a sensation of a foreign body in his larynx. He also had an oxygen saturation of 88%, although no abnormal breath sounds were auscultated. The patient was also hypotensive and tachycardic, with no favorable response after crystalloid administration. He had no neurological alterations but was diaphoretic, with hives spreading across his trunk and all four extremities. Upon further interrogation, we identified that he had consumed diclofenac, a non-steroidal anti-inflammatory drug (NSAID), 45 minutes before the driving incident. Prompt recognition and management of the anaphylactic shock were initiated alongside the assessment and treatment of the traumatic injuries. This case highlights the importance of considering unusual causes of shock in trauma patients. It underscores the need for a comprehensive approach to patient care in trauma settings, where multiple etiologies of shock should be considered and managed simultaneously.

Proteome profiling, biochemical and histological analysis of diclofenac-induced liver toxicity in Yersinia enterocolitica and Lactobacillus fermentum fed rat model: a comparative analysis.

Diclofenac is a hepatotoxic non-steroidal anti-inflammatory drug (NSAID) that affects liver histology and its protein expression levels. Here, we studied the effect of diclofenac on rat liver when co-administrated with either Yersinia enterocolitica strain 8081 serotype O:8 biovar 1B (D*Y) or Lactobacillus fermentum strain 9338 (D*L). Spectroscopic analysis of stool samples showed biotransformation of diclofenac. When compared with each other, D*Y rats lack peaks at 1709 and 1198 cm-1, while D*L rats lack peaks at 1411 cm-1. However, when compared to control, both groups lack peaks at 1379 and 1170 cm-1. Assessment of serum biomarkers of hepatotoxicity indicated significantly altered activities of AST (D*Y: 185.65 ± 8.575 vs Control: 61.9 ± 2.607, D*L: 247.5 ± 5.717 vs Control: 61.9 ± 2.607), ALT (D*Y: 229.8 ± 6.920 vs Control: 70.7 ± 3.109, D*L: 123.75 ± 6.068 vs Control: 70.7 ± 3.109), and ALP (D*Y: 276.4 ± 18.154 vs Control: 320.6 ± 9.829, D*L: 298.5 ± 12.336 vs Control: 320.6 ± 9.829) in IU/L. The analysis of histological alterations showed hepatic sinusoidal dilation with vein congestion and cell infiltration exclusively in D*Y rats along with other histological changes that are common to both test groups, thereby suggesting more pronounced alterations in D*Y rats. Further, LC-MS/MS based label-free quantitation of proteins from liver tissues revealed 74.75% up-regulated, 25.25% down-regulated in D*Y rats and 51.16% up-regulated, 48.84% down-regulated in D*L experiments. The proteomics-identified proteins majorly belonged to metabolism, apoptosis, stress response and redox homeostasis, and detoxification and antioxidant defence that demonstrated the potential damage of rat liver, more pronounced in D*Y rats. Altogether the results are in favor that the administration of lactobacilli somewhat protected the rat hepatic cells against the diclofenac-induced toxicity.