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Cureus Jan 2024Perioperative hypersensitivity reactions vary from mild to potentially fatal anaphylaxis, resulting in significant morbidity and mortality. Most of the perioperative...
Perioperative hypersensitivity reactions vary from mild to potentially fatal anaphylaxis, resulting in significant morbidity and mortality. Most of the perioperative hypersensitivity and allergic reactions are attributed to antibiotics, antiseptic solutions, latex, and opioids. In the current thrust for opioid-free anesthesia, owing to its multiple advantages, paracetamol and nonsteroidal antiinflammatory agents play a significant role in multi-modal pain and inflammatory response management. Nearly nine out of ten individuals experience postoperative pain, one-third experience postoperative nausea and vomiting, and one-fourth experience fever, irrespective of surgery and type of anesthesia, often as an inflammatory response. While perioperative hypersensitivity reactions are common, a patient allergic to multiple commonly used drugs for the treatment of pain, fever, acid-peptic disorder, and nausea and vomiting is scarce. Such cases pose a great challenge in perioperative management. A 14-year-old male child with a traumatic foot drop planned for tibialis posterior tendon transfer developed an allergic reaction with mild fever following an injection of Ranitidine and Ondansetron in the preoperative area. Surgery was deferred and was investigated for allergy profile testing for commonly used drugs, which showed high IgE levels and moderate to severe hypersensitivity for diclofenac and paracetamol. The patient was operated on after one month under spinal anesthesia, avoiding ranitidine, ondansetron, diclofenac, and paracetamol. The following morning, he developed a high-grade fever (102.3° F), which did not resolve with conservative measures. Hypersensitivity and allergic reactions to NSAIDs are reported in the literature. While there are multiple drugs available as NSAIDs, cross-sensitivity or allergy to other drugs within the same group, and even chemically related groups, is also another possibility that needs to be considered while managing such patients. Mefenamic acid controlled the fever, and the child was discharged home after 48 hours of observation. However, the case posed a great perioperative management dilemma; the present report intends to highlight and discuss it.
PubMed: 38410320
DOI: 10.7759/cureus.53015 -
Journal of the American Society of... Jun 2024In hemodialysis, ondansetron initiation versus initiation of lesser QT-prolonging antiemetics associated with higher 10-day sudden cardiac death risk. Analyses...
KEY POINTS
In hemodialysis, ondansetron initiation versus initiation of lesser QT-prolonging antiemetics associated with higher 10-day sudden cardiac death risk. Analyses considering additional cardiac outcomes had consistent findings.
BACKGROUND
Individuals receiving hemodialysis have a high incidence of sudden cardiac death and are susceptible to QT interval–prolonging medication–related cardiac complications. Ondansetron, an antiemetic with known QT-prolonging potential, is associated with fatal arrhythmias in the general population when administered intravenously. The cardiac safety of ondansetron in the hemodialysis population is unknown.
METHODS
We conducted a new-user, active-comparator, cohort study using United States Renal Data System data (2012–2019) to examine the association between the initiation of oral ondansetron versus antiemetics with lesser QT-prolonging potential (promethazine, metoclopramide, or prochlorperazine) and the 10-day risk of sudden cardiac death among individuals receiving hemodialysis. We used inverse probability of treatment-weighted survival models to estimate adjusted hazard ratios, risk differences, and 95% confidence intervals (CIs). We used an intention-to-treat approach in which non-sudden cardiac death was considered a competing event. We examined additional cardiac outcomes in secondary analyses.
RESULTS
Of 119,254 study patients, 64,978 (55%) initiated ondansetron and 54,276 (45%) initiated a comparator antiemetic. Initiation of ondansetron versus a comparator antiemetic was associated with higher relative and absolute 10-day risks of sudden cardiac death (adjusted hazard ratio, 1.44 [95% CI, 1.08 to 1.93]; adjusted risk difference, 0.06% [95% CI, 0.01% to 0.11%]). The number needed to harm was 1688. Analyses of additional cardiac outcomes yielded similar findings.
CONCLUSIONS
Compared with initiation of antiemetics with lesser QT-prolonging potential, initiation of ondansetron was associated with higher short-term cardiac risks among people receiving hemodialysis.
Topics: Humans; Renal Dialysis; Death, Sudden, Cardiac; Ondansetron; Male; Female; Middle Aged; Kidney Failure, Chronic; Antiemetics; Aged
PubMed: 38409683
DOI: 10.1681/ASN.0000000000000336 -
Physiology & Behavior Apr 2024As a frequently occurring complication resulting from brachial plexus avulsion (BPA), neuropathic pain significantly impacts the quality of life of patients and places a...
PURPOSE
As a frequently occurring complication resulting from brachial plexus avulsion (BPA), neuropathic pain significantly impacts the quality of life of patients and places a substantial burden on their families. Recent reports have suggested that the 5-HT3a receptor may play a role in the development and regulation of neuropathic pain. The current study aimed to explore the involvement of the 5-HT3a receptor in neuropathic pain resulting from BPA in rats.
METHODS
A rat model of neuropathic pain was induced through brachial plexus avulsion (BPA). The pain thresholds of the rats were measured after BPA. The spinal dorsal horn (SDH) of rats was collected at day 14 after surgery, and the expression and distribution of the 5-HT3a receptor were analyzed using immunohistochemistry and western blotting. The expression levels of various factors related to central sensitization were measured by western blot, including c-Fos, GFAP, IBA-1, IL-1β and TNF-α. The effects of 5-HT3a receptor antagonists on hyperalgesia were assessed through behavioral tests after intrathecal administration of ondansetron. Additionally, at 120 min postinjection, the SDH of rats was acquired, and the change of expression levels of protiens related to central sensitization were measured by western blot.
RESULTS
BPA induced mechanical and cold hypersensitivity in rats. The 5-HT3a receptor was increased and mainly distributed on neurons and microglia in the SDH after BPA, and the level of central sensitization and expression of inflammatory factors, such as c-Fos, GFAP, IBA-1, IL-1β and TNF-α, were also increased markedly. Ondansetron, which is a selective 5-HT3a receptor antagonist, reversed the behavioral changes caused by BPA. The antagonist also decreased the expression of central sensitization markers and inflammatory factors.
CONCLUSION
The results suggested that the 5-HT3a receptor is involved in neuropathic pain by regulating central nervous system sensitization in a rat brachial plexus avulsion model. Targeting the 5-HT3a receptor may be a promising approach for treating neuropathic pain after brachial plexus avulsion.
Topics: Humans; Rats; Animals; Central Nervous System Sensitization; Tumor Necrosis Factor-alpha; Ondansetron; Quality of Life; Brachial Plexus; Neuralgia; Hyperalgesia
PubMed: 38403260
DOI: 10.1016/j.physbeh.2024.114503 -
Journal of Personalized Medicine Jan 2024There are currently no established methods to predict quantitatively whether the start of a drug with the potential to prolong the QTc interval poses patients at risk...
There are currently no established methods to predict quantitatively whether the start of a drug with the potential to prolong the QTc interval poses patients at risk for relevant QTc prolongation. Therefore, this retrospective study aimed to pave the way for the development of models for estimating QTc prolongation in patients newly exposed to medications with QTc-prolonging potential. Data of patients with a documented QTc prolongation after initiation of a QTc-prolonging drug were extracted from hospital charts. Using a standard model-building approach, general linear mixed models were identified as the best models for predicting both the extent of QTc prolongation and its absolute value after the start of a QTc-time-prolonging drug. The cohort consisted of 107 adults with a mean age of 64.2 years. Patients were taking an average of 2.4 drugs associated with QTc prolongation, with amiodarone, propofol, pipamperone, ondansetron, and mirtazapine being the most frequently involved. There was a significant but weak correlation between measured and predicted absolute QTc values under medication (r = 0.262, < 0.05), as well as for QTc prolongation (r = 0.238, < 0.05). As the developed models are based on a relatively small number of subjects, further research is necessary to ensure their applicability and reliability in real-world scenarios. Overall, this research contributes to the understanding of QTc prolongation and its association with medications, providing insight into the development of predictive models. With improvements, these models could potentially aid healthcare professionals in assessing the risk of QTc prolongation before adding a new drug and in making informed decisions in clinical settings.
PubMed: 38392605
DOI: 10.3390/jpm14020172 -
The Journal of Emergency Medicine Jan 2024
Topics: Child; Humans; Ondansetron; Antiemetics; Long QT Syndrome; Craniocerebral Trauma
PubMed: 38342508
DOI: 10.1016/j.jemermed.2023.08.007 -
Translational Pediatrics Jan 2024Neurokinin-1 receptor antagonists have improved the management of chemotherapy-induced nausea and vomiting (CINV), but to date there has been no prospective comparison...
Comparison of oral aprepitant and intravenous fosaprepitant for prevention of chemotherapy-induced nausea and vomiting in pediatric oncology patients: a randomized phase III trial.
BACKGROUND
Neurokinin-1 receptor antagonists have improved the management of chemotherapy-induced nausea and vomiting (CINV), but to date there has been no prospective comparison between oral aprepitant and intravenous fosaprepitant in pediatric oncology patients.
METHODS
Our study was a double-parallel study, and the distribution ratio was 1:1. Children aged 2-12 years who were undergoing moderate or highly emetogenic chemotherapy (MEC or HEC) were randomly assigned to receive ondansetron and dexamethasone combined with either a single dose of intravenous fosaprepitant (arm A), or 3 days of oral aprepitant (arm B). The primary outcome measure was the rate of complete response (CR) of CINV within the acute phase, defined as from the start through 24 hours after the last chemotherapy dose. Response during the delayed phase, overall response, and use of rescue antiemetics were also assessed.
RESULTS
We prospectively evaluated 108 eligible patients, including 55 receiving fosaprepitant. Study observations were made during a single cycle for each patient. The occurrence of CR in the acute phase was statistically higher for patients receiving fosaprepitant (95% 79%, P=0.018<0.05). Modest differences were seen in CR rates during the delayed phase (71% 66%, P=0.586), and overall response rate (69% 57%, P=0.179). The use of antiemetic rescue medicines was similar between arms A (11%) and B (7%).
CONCLUSIONS
Fosaprepitant produced more CRs of CINV in the acute phase than did aprepitant, although there were no statistical differences in delayed phase response, overall response, or use of rescue antiemetics. This study confirms the safety, efficacy, and potential advantages of fosaprepitant in reducing CINV in pediatric oncology patients.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT04873284.
PubMed: 38323173
DOI: 10.21037/tp-23-598 -
Cureus Jan 2024This article presents the case of a 21-year-old female with a psychiatric history of depression and a history of chronic cannabis use who presented to the emergency...
This article presents the case of a 21-year-old female with a psychiatric history of depression and a history of chronic cannabis use who presented to the emergency department after overdosing on ondansetron and was urine test positive for marijuana (tetrahydrocannabinol (THC)). The patient was later transferred to a psychiatric unit for further evaluation, and after six days of hospitalization and cessation of marijuana, the patient demonstrated gradual improvement in her mental status examination and was deemed fit for discharge with follow-up instructions. This case illustrates the effect of cannabis use and cannabis use disorder on those with major depressive disorder (MDD), the component of cannabis that worsens the symptoms of depression, the role of the endocannabinoid system (ECS) in depression, and available treatments.
PubMed: 38322065
DOI: 10.7759/cureus.51803 -
Neurogastroenterology and Motility Apr 2024Lactulose is a laxative which accelerates transit and softens stool. Our aim was to investigate its mechanism of action and use this model of diarrhea to investigate the... (Randomized Controlled Trial)
Randomized Controlled Trial
Mechanisms underlying the laxative effect of lactulose: A randomized placebo-controlled trial showing increased small bowel water and motility unaltered by the 5-HT receptor antagonist, ondansetron.
BACKGROUND
Lactulose is a laxative which accelerates transit and softens stool. Our aim was to investigate its mechanism of action and use this model of diarrhea to investigate the anti-diarrheal actions of ondansetron.
METHODS
A double-blind, randomized, placebo-controlled crossover study of the effect of ondansetron 8 mg in 16 healthy volunteers. Serial MRI scans were performed fasted and 6 h after a meal. Participants then received lactulose 13.6 g twice daily and study drug for a further 36 h. On Day 3, they had further serial MRI scans for 4 h. Measurements included small bowel water content (SBWC), colonic volume, colonic gas, small bowel motility, whole gut transit, and ascending colon relaxation time (T1AC), a measure of colonic water content.
KEY RESULTS
Lactulose increased area under the curve (AUC) of SBWC from 0 to 240 min, mean difference 14.2 L · min (95% CI 4.1, 24.3), p = 0.009, and substantially increased small bowel motility after 4 h (mean (95% CI) 523 (457-646) a.u. to 852 (771-1178) a.u., p = 0.007). There were no changes in T1AC after 36 h treatment. Ondansetron did not significantly alter SBWC, small bowel motility, transit, colonic volumes, colonic gas nor T1AC, with or without lactulose.
CONCLUSION & INFERENCES
Lactulose increases SBWC and stimulates small bowel motility; however, unexpectedly it did not significantly alter colonic water content, suggesting its laxative effect is not osmotic but due to stimulation of motility. Ondansetron's lack of effect on intestinal water suggests its anti-diarrheal effect is not due to inhibition of secretion but more likely altered colonic motility.
Topics: Humans; Lactulose; Laxatives; Ondansetron; Serotonin; Water; Cross-Over Studies; Colon; Gastrointestinal Transit
PubMed: 38316636
DOI: 10.1111/nmo.14754 -
BJOG : An International Journal of... Jun 2024An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be...
An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (Appendix III). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in Appendix III. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C].
Topics: Humans; Female; Pregnancy; Hyperemesis Gravidarum; Antiemetics; Ondansetron; Morning Sickness; Nausea; Pyridoxine; Metoclopramide; Severity of Illness Index; Pregnancy Complications
PubMed: 38311315
DOI: 10.1111/1471-0528.17739 -
European Journal of Pharmacology Mar 2024Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to...
Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to understand its pathogenesis to manage it better. Thus, we explored the involvement of peripheral mast cells in an experimental model of fibromyalgia induced by reserpine. Reserpine (1 mg/kg) was subcutaneously (s.c.) injected once daily in the back of male Swiss mice for three consecutive days. We analysed mechanical and cold allodynia, muscle fatigue and number of mast cell in plantar tissue. The fibromyalgia induction produced mast cell infiltration (i.e., mastocytosis) in the mice's plantar tissue. The depletion of mast cell mediators with the compound 48/80 (0.5-4 mg/kg, intraperitoneal (i.p.)) or the mast cell membrane stabilizer ketotifen fumarate (10 mg/kg, oral route (p.o.) widely (80-90 %) and extensively (from 1 up to 10 days) prevented reserpine-induced mechanical and cold allodynia and muscle fatigue. Compound 48/80 also prevented the reserpine-induced mastocytosis. Finally, we demonstrated that PAR-2, 5-HT, 5-HT, H, NK1 and MrgprB2 receptors, expressed in neuronal or mast cells, seem crucial to mediate fibromyalgia-related cardinal symptoms since antagonists or inhibitors of these receptors (gabexate (10 mg/kg, s.c.), ENMD-1068 (10 mg/kg, i.p.), ketanserin (1 mg/kg, i.p.), ondansetron (1 mg/kg, p.o.), promethazine (1 mg/kg, i.p.), and L733,060 (5 mg/kg, s.c.), respectively) transiently reversed the reserpine-induced allodynia and fatigue. The results indicate that mast cells mediate painful and fatigue behaviours in this fibromyalgia model, representing potential therapy targets to treat fibromyalgia syndrome.
Topics: Mice; Male; Animals; Fibromyalgia; Mast Cells; Hyperalgesia; Serotonin; Reserpine; Mastocytosis
PubMed: 38311276
DOI: 10.1016/j.ejphar.2024.176385