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Circulation Oct 2023In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory... (Review)
Review
2023 American Heart Association Focused Update on the Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.
In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, β-adrenergic receptor antagonists (also known as β-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.
Topics: Humans; Adrenergic beta-Antagonists; American Heart Association; Benzodiazepines; Cardiopulmonary Resuscitation; Digoxin; Heart Arrest; United States
PubMed: 37721023
DOI: 10.1161/CIR.0000000000001161 -
The Lancet. Child & Adolescent Health Feb 2020Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse... (Review)
Review
Despite ototoxicity being a prevalent consequence of cisplatin chemotherapy, little guidance exists on interventions to prevent this permanent and progressive adverse event. To develop a clinical practice guideline for the prevention of cisplatin-induced ototoxicity in children and adolescents with cancer, we convened an international, multidisciplinary panel of experts and patient advocates to update a systematic review of randomised trials for the prevention of cisplatin-induced ototoxicity. The systematic review identified 27 eligible adult and paediatric trials that evaluated amifostine, sodium diethyldithiocarbamate or disulfiram, systemic sodium thiosulfate, intratympanic therapies, and cisplatin infusion duration. Regarding systemic sodium thiosulfate, the panel made a strong recommendation for administration in non-metastatic hepatoblastoma, a weak recommendation for administration in other non-metastatic cancers, and a weak recommendation against its routine use in metastatic cancers. Amifostine, sodium diethyldithiocarbamate, and intratympanic therapy should not be routinely used. Cisplatin infusion duration should not be altered as a means to reduce ototoxicity. Further research to determine the safety of sodium thiosulfate in patients with metastatic cancer is encouraged.
Topics: Adolescent; Antineoplastic Agents; Child; Cisplatin; Female; Hearing Loss; Humans; Male; Neoplasms; Ototoxicity; Prognosis; Randomized Controlled Trials as Topic; Survival Rate; Thiosulfates
PubMed: 31866182
DOI: 10.1016/S2352-4642(19)30336-0 -
Journal of the American Society of... May 2022Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. Evidence-based interventions that may attenuate its progression in...
BACKGROUND
Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. Evidence-based interventions that may attenuate its progression in CKD remain uncertain.
METHODS
We conducted a systematic review of prospective clinical trials of interventions to attenuate vascular calcification in people with CKD, compared with placebo, another comparator, or standard of care. We included prospective clinical trials (randomized and nonrandomized) involving participants with stage 3-5D CKD or kidney transplant recipients; the outcome was vascular calcification measured using radiologic methods. Quality of evidence was determined by the Cochrane risk of bias assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.
RESULTS
There were 77 trials (63 randomized) involving 6898 participants eligible for inclusion (median sample size, 50; median duration, 12 months); 58 involved participants on dialysis, 15 involved individuals with nondialysis CKD, and 4 involved kidney transplant recipients. Risk of bias was moderate over all. Trials involving magnesium and sodium thiosulfate consistently showed attenuation of vascular calcification. Trials involving intestinal phosphate binders, alterations in dialysate calcium concentration, vitamin K therapy, calcimimetics, and antiresorptive agents had conflicting or inconclusive outcomes. Trials involving vitamin D therapy and HMG-CoA reductase inhibitors did not demonstrate attenuation of vascular calcification. Mixed results were reported for single studies of exercise, vitamin E-coated or high-flux hemodialysis membranes, interdialytic sodium bicarbonate, SNF472, spironolactone, sotatercept, nicotinamide, and oral activated charcoal.
CONCLUSIONS
Currently, there are insufficient or conflicting data regarding interventions evaluated in clinical trials for mitigation of vascular calcification in people with CKD. Therapy involving magnesium or sodium thiosulfate appears most promising, but evaluable studies were small and of short duration.
Topics: Female; Humans; Magnesium; Male; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic; Vascular Calcification
PubMed: 35232774
DOI: 10.1681/ASN.2021101327 -
Journal of Education & Teaching in... Jul 2022The goal of this simulation is to educate emergency medicine students, residents, attending physicians, and mid-level practitioners to recognize, diagnose, and manage...
AUDIENCE
The goal of this simulation is to educate emergency medicine students, residents, attending physicians, and mid-level practitioners to recognize, diagnose, and manage acute cyanide toxicity.
INTRODUCTION
Cyanide has an almond scent and is a naturally occurring compound. It is present within many different types of plants and fruits including apricots, apples, peaches, lima beans, and cassava plants but is harmless.1 The trace amounts of cyanide found within organic materials is of little concern because its high reactivity causes it to be metabolized rapidly and create other compounds. However, modern synthetic materials such as plastics, papers, textiles, and machinery can release a much greater concentration of hydrogen cyanide when exposed to high temperatures.1 As the use of contemporary nitrogen-containing synthetic polymers has expanded, the possibility of cyanide toxicity has become increasingly common and severe. Hydrogen cyanide is especially dangerous to humans because the gaseous form reacts quickly upon inhalation.2When cyanide enters the body via inhalation, it blocks the cells from utilizing oxygen by binding to the cytochrome oxidase in the mitochondria.2 The inability of the cell to use oxygen forces cells from aerobic metabolism into anaerobic metabolism. Anaerobic metabolism results in the production of lactic acid, which causes metabolic acidosis.3 The human body cannot sustain itself with the lack of oxygen and anaerobic metabolism for a prolonged period of time. Ultimately, the body will suffer cardiorespiratory arrest.1Symptoms of cyanide toxicity include headache, nausea, shortness of breath, and altered mental status.1 These are similar to those of carbon monoxide and carbon dioxide inhalation. However, symptoms of cyanide toxicity cannot be treated with supplemental oxygen as carbon monoxide and carbon dioxide are. Cyanide toxicity must be treated with an antidote - sodium thiosulfate, sodium nitrite, and hydroxocobalamin.4 Each of the antidotes works by binding with the highly reactive cyanide, neutralizing the compound, and converting it into a water-soluble product that will be cleared through renal excretion.4Fire victims often present to the emergency department critically ill. They will likely have obvious external thermal burns and traumatic injuries; however, it is important for emergency personnel to recognize the respiratory distress and metabolic derangements that are most likely occurring due to toxic gas inhalation. People who are trapped within a burning structure are exposed to carbon monoxide, carbon dioxide, and cyanide from the combustion of contents within the building. These toxic gasses will cause severe tissue hypoxia without significant vital sign changes.5 The respiratory distress and metabolic compromise will be acutely more fatal than the obvious external injuries and burns. The challenge in treating these patients is for the healthcare team to know the differential diagnoses, prioritize airway, breathing and circulation, and to empirically treat the patient as if they have a confirmed exposure.It is estimated that 35% of all fire victims have toxic levels of cyanide upon arrival to the emergency room.2 Acute cyanide toxicity can become fatal within minutes; however, a prompt diagnosis and treatment can be lifesaving. Unfortunately, due to the limited amount of time the human body can sustain anaerobic metabolism and tissue hypoxia, blood test results are not available in time to be clinically applicable.2 Rather, the emergency room personnel must begin treatment immediately upon recognizing that toxic smoke inhalation may have occurred.We understand the importance of knowing how to treat fire victims. Therefore, the goal of this simulation case is to expose the emergency providers to cyanide poisoning and educate emergency providers about the critical steps of how to approach, diagnose, and treat cyanide toxicity.
EDUCATIONAL OBJECTIVES
After the completion of this simulation, participants will have learned how to: 1) identify clues of smoke inhalation based on a physical examination; 2) identify smoke inhalation-induced airway compromise and perform definitive management; 3) create a differential diagnosis for victims of fire cyanide poisoning, carbon monoxide, and carbon dioxide; 4) appropriately treat cyanide poisoning; 5) demonstrate the importance of preemptively treating for cyanide poisoning; 6) perform an initial physical examination and identify physical marks suggesting the patient is a fire and smoke inhalation victim; and 7) familiarize themselves with the Cyanokit and treatment with hydroxocobalamin.
EDUCATIONAL METHODS
This is a high-fidelity simulation case in which participants work through a case of a patient who has been exposed to fire. The participants will be able to work hands-on to evaluate, diagnose, and treat cyanide poisoning in an emergency event. Afterwards, there will be a small group discussion and debriefing of the case in order to review patient care skills, interpersonal and communication skills, medical knowledge, and system-based practice.
RESEARCH METHODS
The participants were instructed to complete a survey before and after the simulation case. A quality Likert Scale was used to assess the participants' comfort level of diagnosing, treating, and managing a patient with toxic smoke inhalation. A score of 1 represented a negative experience and 5 represented a very positive experience. The surveys were then reviewed by the research team to determine if the simulation case improved the participants' comfort level. The survey answers were compared collectively, as well as individually, and were analyzed between the pre-simulation and post-simulation results.
RESULTS
Our simulation involved 25 participants: 20 participants were emergency medicine resident physicians and 5 were 4th-year medical students. In the pre-simulation survey, participants reported a mean of 2.7 out of 5 when asked to rate their confidence in their ability to treat a smoke inhalation victim. The post-simulation survey showed a significant increase to a mean of 3.5 out of 5. Participants were also asked to evaluate the usefulness of the simulation: 15 participants rated the case as a 5, which represented "very useful," and the other 10 participants rated the case as a 4, which represented "useful." The mean value when asked to assess the simulation case's usefulness and applicability in emergency medicine was 4.6 out of 5.
DISCUSSION
This simulation allows providers to focus on victims of fire. Fire victims are often critically ill and require time sensitive treatment. This simulation gives providers a chance to review their knowledge and prepare them for real life cases. Based on the survey results, the simulation improved awareness and understanding of the symptoms of acute cyanide toxicity and improved the participant's ability to recognize, diagnose, and treat cyanide poisoning.
TOPICS
Cyanide toxicity, carbon monoxide toxicity, cyanide antidote, fire victim, intubation, airway intervention, oxygen treatment, history taking, lab testing ordering, symptom identification, interpretation of lab results, emergency medicine simulation.
PubMed: 37465777
DOI: 10.21980/J80W76 -
Current Opinion in Rheumatology Nov 2022The aim of this study was to provide updated information on the prevalence, pathogenesis, diagnostics and therapeutics of calcinosis cutis associated with systemic... (Review)
Review
PURPOSE OF REVIEW
The aim of this study was to provide updated information on the prevalence, pathogenesis, diagnostics and therapeutics of calcinosis cutis associated with systemic sclerosis (SSc).
RECENT FINDINGS
Observational studies show ethnic and geographical differences in the prevalence of calcinosis. In addition to clinical and serological associations, biochemical studies and in-vivo models have attempted to explain theories behind its pathogenesis, including prolonged state of inflammation, mechanical stress, hypoxia and dysregulation in bone and phosphate metabolism. Long-term use of proton pump inhibitors may increase the risk for calcinosis in SSc. Few single-centre observational studies have shown mild benefit with minocycline and topical sodium thiosulfate.
SUMMARY
Calcinosis cutis is the deposition of insoluble calcium in the skin and subcutaneous tissues. It affects up to 40% of SSc patients and causes significant morbidity. Long disease duration, features of vascular dysfunction and osteoporosis have been associated with calcinosis. Altered levels of inorganic pyrophosphate and fibroblast growth factor-23 have been implicated in dysregulated phosphate metabolism that may lead to calcinosis in SSc. Plain radiography can help with diagnosis and quantifying the calcinosis burden. Surgical treatment remains the most effective therapy when feasible. At present, no medical therapies have proven efficacy in large randomized controlled trials.
Topics: Calcinosis; Calcium; Diphosphates; Humans; Minocycline; Proton Pump Inhibitors; Scleroderma, Systemic
PubMed: 35993867
DOI: 10.1097/BOR.0000000000000896 -
JAMA Network Open Apr 2023Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label therapeutic in calciphylaxis, but there is a lack of clinical trials and studies that demonstrate its effect compared with those without STS treatment.
OBJECTIVE
To perform a meta-analysis of the cohort studies that provided data comparing outcomes among patients with calciphylaxis treated with and without intravenous STS.
DATA SOURCES
PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using relevant terms and synonyms including sodium thiosulphate and calci* without language restriction.
STUDY SELECTION
The initial search was for cohort studies published before August 31, 2021, that included adult patients diagnosed with CKD experiencing calciphylaxis and could provide a comparison between patients treated with and without intravenous STS. Studies were excluded if they reported outcomes only from nonintravenous administration of STS or if the outcomes for CKD patients were not provided.
DATA EXTRACTION AND SYNTHESIS
Random-effects models were performed. The Egger test was used to measure publication bias. Heterogeneity was assessed using the I2 test.
MAIN OUTCOMES AND MEASURES
Skin lesion improvement and survival, synthesized as ratio data by a random-effects empirical Bayes model.
RESULTS
Among the 5601 publications retrieved from the targeted databases, 19 retrospective cohort studies including 422 patients (mean age, 57 years; 37.3% male) met the eligibility criteria. No difference was observed in skin lesion improvement (12 studies with 110 patients; risk ratio, 1.23; 95% CI, 0.85-1.78) between the STS and the comparator groups. No difference was noted for the risk of death (15 studies with 158 patients; risk ratio, 0.88; 95% CI, 0.70-1.10) and overall survival using time-to-event data (3 studies with 269 participants; hazard ratio, 0.82; 95% CI, 0.57-1.18). In meta-regression, lesion improvement associated with STS negatively correlated with publication year, implying that recent studies are more likely to report a null association compared with past studies (coefficient = -0.14; P = .008).
CONCLUSIONS AND RELEVANCE
Intravenous STS was not associated with skin lesion improvement or survival benefit in patients with CKD experiencing calciphylaxis. Future investigations are warranted to examine the efficacy and safety of therapies for patients with calciphylaxis.
Topics: Adult; Humans; Male; Middle Aged; Female; Calciphylaxis; Retrospective Studies; Bayes Theorem; Renal Insufficiency, Chronic
PubMed: 37099293
DOI: 10.1001/jamanetworkopen.2023.10068 -
Ugeskrift For Laeger Jan 2024Calciphylaxis is a rare condition characterised by painful necroses due to microvascular calcifications. It primarily affects individuals with end-stage renal disease...
Calciphylaxis is a rare condition characterised by painful necroses due to microvascular calcifications. It primarily affects individuals with end-stage renal disease and affected calcium-phosphate metabolism. This is a case report of a 55-year-old woman with end-stage renal disease who developed a necrotic ulcer at the breast due to calciphylaxis. Although treated with sodium thiosulfate and hyperbaric oxygen, the ulcer progressed and multiple necrotic calciphylaxis ulcers appeared. The treatment options and wound management are discussed while focusing on indications for surgical debridement.
Topics: Female; Humans; Middle Aged; Calciphylaxis; Calcium; Kidney Failure, Chronic; Ulcer
PubMed: 38235723
DOI: 10.61409/V08230540 -
International Journal of Molecular... Jun 2021Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (HS), an endogenous signaling molecule and the third member of the... (Review)
Review
Thiosulfate in the form of sodium thiosulfate (STS) is a major oxidation product of hydrogen sulfide (HS), an endogenous signaling molecule and the third member of the gasotransmitter family. STS is currently used in the clinical treatment of acute cyanide poisoning, cisplatin toxicities in cancer therapy, and calciphylaxis in dialysis patients. Burgeoning evidence show that STS has antioxidant and anti-inflammatory properties, making it a potential therapeutic candidate molecule that can target multiple molecular pathways in various diseases and drug-induced toxicities. This review discusses the biochemical and molecular pathways in the generation of STS from HS, its clinical usefulness, and potential clinical applications, as well as the molecular mechanisms underlying these clinical applications and a future perspective in kidney transplantation.
Topics: Animals; Gastrointestinal Hormones; Humans; Hydrogen Sulfide; Metabolic Networks and Pathways; Oxidation-Reduction; Reperfusion Injury; Thiosulfates
PubMed: 34208631
DOI: 10.3390/ijms22126452 -
Cell Stress & Chaperones Sep 2020Near the end of 2019, SARS-CoV-2, a novel highly contagious coronavirus phylogenetically related to the SARS virus, entered the human population with lethal...
Near the end of 2019, SARS-CoV-2, a novel highly contagious coronavirus phylogenetically related to the SARS virus, entered the human population with lethal consequences. This special issue devoted to the resulting disease COVID-19 was not planned but instead the articles accumulated organically as researchers in the cell stress response field noticed similarities among the pathophysiology of COVID-19 infections and the responses that they studied in contexts unrelated to viral infection. We preface the issue with an introductory article which begins with a brief review of the structure and biology of SARS-CoV-2. As we collected and compared the COVID-19 articles, several shared themes emerged. In the second part of the introduction, each article is summarized briefly and the common themes that link each into a spontaneously arising chain of ideas and hypotheses are emphasized. These themes include growing evidence of molecular mimicry among the viral proteins and the proteins of patients. The realization that much of the consequences of such immune mimicry may play out on the plasma membrane of vascular endothelial cells raised the specter of autoimmune-induced vascular endothelial damage in multiple organs. Proposals of new therapeutic approaches have coalesced around the theme of inducing protection of the vascular endothelium. New chemical treatments that are proposed include stannous chloride, inducers of the gasotransmitter hydrogen sulfide such as sodium thiosulfate and inducers of the cytoprotective stress protein heme oxygenase. Oxygen delivered by ventilators is already in extensive use to provide life support for patients with severe COVID-19. Two articles propose to advance the use of oxygen to the level of a therapeutic treatment early in the detection of the virus in infected patients by delivering oxygen under elevated pressure in hyperbaric chambers. At elevated blood plasma concentrations, hyperbaric oxygen is capable of achieving results far beyond the capability of ventilators as it promotes the activation of transcription factors that control the establishment of inducible cellular defense systems.
Topics: COVID-19; Coronavirus; Coronavirus Infections; Endothelial Cells; Humans; Oxygen; Pandemics; Pneumonia, Viral; Viral Proteins
PubMed: 32889638
DOI: 10.1007/s12192-020-01155-4