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1.
Toxins (Basel) ; 13(11)2021 10 30.
Article En | MEDLINE | ID: mdl-34822553

Uremic pruritus is a distressful complication of chronic kidney disease and results in impaired quality of life and higher mortality rates. Intravenous sodium thiosulfate has been reported to alleviate pruritus in hemodialysis patients. We performed a systematic review and meta-analysis to estimate the efficacy of intravenous sodium thiosulfate in patients with uremic pruritus. A systematic search of electronic databases up to June 2021 was conducted for randomized controlled trials that evaluated the clinical effects of sodium thiosulfate in the management of patients with uremic pruritus. Two reviewers selected eligible articles and evaluated the risk of bias; the results of pruritus assessment and uremic pruritus-related laboratory parameters in selected studies were analyzed. There are four trials published between 2018 and 2021, which include 222 participants. The sodium thiosulfate group displayed significant decrease in the pruritus score (standardized mean difference = -3.52, 95% confidence interval = -5.63 to -1.41, p = 0.001), without a significant increase in the adverse effects (risk ratio = 2.44, 95% confidence interval = 0.37 to 15.99, p = 0.35) compared to the control group. Administration of sodium thiosulfate is found to be a safe and efficacious complementary therapy in improving uremic pruritus in patients with chronic kidney disease.


Antioxidants/adverse effects , Pruritus/drug therapy , Thiosulfates/adverse effects , Uremia/drug therapy , Vasodilator Agents/adverse effects , Antioxidants/pharmacology , Humans , Pruritus/etiology , Randomized Controlled Trials as Topic , Thiosulfates/pharmacology , Uremia/complications , Vasodilator Agents/pharmacology
2.
Zebrafish ; 17(5): 342-353, 2020 10.
Article En | MEDLINE | ID: mdl-33048660

Embryo surface disinfection is utilized in aquaculture to decrease the risk of pathogen introduction into established colonies. Zebrafish embryos are commonly disinfected with unbuffered sodium hypochlorite at 25-50 ppm for 10 min with or without concurrent treatment with chemicals, including pronase (Pron), sodium thiosulfate, and/or methylene blue; however, the impact of these chemicals on embryo survival and development has not been evaluated. In this study, AB and casper embryos were exposed to disinfection protocols that used Pron, sodium thiosulfate, and/or methylene blue (given alone, in various combinations, or all three combined) with 50 and 100 ppm sodium hypochlorite performed 6 and 24 h postfertilization (HPF). All groups were evaluated for survival, hatching, and malformations at 5 days postfertilization. Maximal survival (69%-97%) and hatching rates (66%-94%) were generally observed with sodium hypochlorite disinfection followed by exposure to both Pron and sodium thiosulfate and maintenance in standard embryo medium without methylene blue. Methylene blue had variable effects on survival and hatching. Higher survival and hatching rates were seen in AB embryos disinfected at 6 HPF and casper embryos disinfected at 24 HPF. Susceptibility to sodium hypochlorite toxicity differed by strain, emphasizing the need to test disinfection protocols on small embryo cohorts.


Disinfectants/adverse effects , Embryonic Development/drug effects , Methylene Blue/adverse effects , Pronase/adverse effects , Sodium Hypochlorite/adverse effects , Thiosulfates/adverse effects , Zebrafish/physiology , Animals , Disinfection , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/embryology , Zebrafish/embryology , Zebrafish/growth & development
3.
J Interv Cardiol ; 2020: 6014915, 2020.
Article En | MEDLINE | ID: mdl-33041696

BACKGROUND: In animal studies, hydrogen sulfide (H2S) has been shown to protect the heart from ischemia-reperfusion injury. This study evaluates the safety and tolerability of the H2S donor sodium thiosulfate (STS) in patients with acute coronary syndrome (ACS). METHODS: Eighteen patients, undergoing coronary angiography for ACS, received STS intravenously immediately after arrival at the catheterization laboratory according to a "3 + 3 dose-escalation design" with fixed dosing endpoint (0, 2.5, 5, 10, 12.5, and 15 grams). This first dose STS was combined with verapamil and nitroglycerin required for transradial procedures. A second dose STS was administered 6 hours later. Primary endpoint was dose-limiting toxicity, defined as significant hemodynamic instability or death up to 24 hours or before discharge from the coronary care unit. Secondary outcomes included the occurrence of anaphylaxis, nausea, vomiting, and systolic blood pressure (SBP) course. RESULTS: Sixteen patients received two dosages of STS and two patients one dosage. None of the patients reached the primary endpoint, nor experienced a serious adverse event. We observed a clinically well-tolerated decline in SBP 1 hour after administration of the first STS dose and concomitant verapamil/nitroglycerin. SBP for all patients together reduced 16.8 (8.1-25.5) mmHg (P = 0.0008). No significant decline in SBP occurred after the second dose. Mild nausea was observed in one patient. CONCLUSION: This is the first report on sodium thiosulfate administration in patients with acute coronary syndromes. Our data suggest that sodium thiosulfate was well tolerated in this setting. The potential benefit of this intervention has to be examined in larger studies.


Acute Coronary Syndrome/diagnosis , Coronary Angiography , Myocardial Reperfusion Injury/prevention & control , Thiosulfates , Adult , Coronary Angiography/adverse effects , Coronary Angiography/methods , Dose-Response Relationship, Drug , Female , Humans , Male , Middle Aged , Myocardial Reperfusion Injury/etiology , Pilot Projects , Protective Agents/administration & dosage , Protective Agents/adverse effects , Thiosulfates/administration & dosage , Thiosulfates/adverse effects
4.
Ren Fail ; 42(1): 987-993, 2020 Nov.
Article En | MEDLINE | ID: mdl-32967516

OBJECTIVES: This study aimed to compare the efficacy of intravenous sodium thiosulfate (IV STS) with that of loratadine in the treatment of uremic pruritus in hemodialysis (HD) patients. METHODS: This retrospective study included 44 HD patients with pruritus aged over 18 years between June 2018 and January 2020 at the Aerospace Center Hospital of China. Twenty-four HD patients received 3.2 g IV STS treatment three times per week at the end of each HD session for 8 weeks. Twenty HD patients received loratadine (10 mg/day) for 8 weeks. Pruritus intensity was measured using a visual analog scale (VAS) and the detailed pruritus score (DPS) at three time points. The safety of STS was evaluated according to adverse event symptoms and biological variable changes. RESULTS: There was no significant difference between the STS and loratadine groups in age, sex, characteristics of pruritus, or other clinical variables before treatment. After 8 weeks of treatment, the VAS score (7.07 ± 2.56 and 2.67 ± 2.01) and DPS (30.72 ± 4.81 and 8.04 ± 2.86) decreased significantly in the STS group (p < 0.05). The mean decrease in VAS score (6.89 ± 1.98 and 6.34 ± 2.35) and DPS (28.90 ± 3.24 and 26.92 ± 2.41) in the loratadine group was not statistically significant (p > 0.05). There were no morbidities or mortalities associated with the use of either drug. All biological variables remained stable after therapy. CONCLUSIONS: STS can improve uremic pruritus in HD patients. However, literature on the subject remains lacking. Close monitoring for adverse effects is advised.


Pruritus/drug therapy , Pruritus/etiology , Renal Dialysis , Thiosulfates/administration & dosage , Uremia/complications , Administration, Intravenous , Adult , Aged , Aged, 80 and over , China , Female , Humans , Male , Middle Aged , Retrospective Studies , Thiosulfates/adverse effects , Uremia/blood , Uremia/therapy , Visual Analog Scale
5.
Am J Case Rep ; 21: e919926, 2020 Apr 27.
Article En | MEDLINE | ID: mdl-32336746

BACKGROUND Calcific uremic arteriolopathy (CUA) is a rare and incredibly painful cutaneous disorder secondary to microvascular involvement in which calcium dysregulation leads to stenosis of medium sized arterial blood vessels along with endothelial dysregulation and thrombosis. Ultimately, these patients are at high risk for non-healing wounds with risk of death from sepsis and multi-organ failure. It is a poorly understood condition with limited therapies that do not offer mortality benefit. Prevalence is about 4% in hemodialysis patients. Sodium thiosulfate (STS) can be used in hemodialysis patients but therapy is often limited by the development of high anion gap metabolic acidosis. CASE REPORT A 53-year-old male who had end stage renal disease and who was on hemodialysis and taking warfarin for bio-prosthetic mitral valve replacement and atrial fibrillation presented with non-healing right lower extremity cellulitis which had failed outpatient treatment. A skin biopsy of the lesion was consistent with CUA. The patient failed to improve on calcitriol and cinacalcet and was started on intravenous STS. Subsequently, he developed life threatening metabolic acidosis requiring a bicarbonate drip. He died 12 weeks after his initial diagnosis of CUA. CONCLUSIONS This article seeks to describe how the treatment of CUA; a rare disease with high mortality, is limited by the development of metabolic acidosis when using STS therapy. There is an 80% mortality rate within 6 months from CUA with major adverse effect of a high anion gap metabolic acidosis. Further research is needed in the field of establishing optimal dosing and frequency.


Acidosis/chemically induced , Calciphylaxis/diagnosis , Calciphylaxis/therapy , Thiosulfates/adverse effects , Chelating Agents/adverse effects , Comorbidity , Fatal Outcome , Humans , Kidney Failure, Chronic/complications , Male , Middle Aged
6.
Invest New Drugs ; 38(5): 1463-1471, 2020 10.
Article En | MEDLINE | ID: mdl-32157599

Cisplatin is a widely used chemotherapy for the treatment of certain solid tumors. Ototoxicity and subsequent permanent hearing loss remain a serious dose-limiting side effect associated with cisplatin treatment. To date, no therapies have been approved to prevent or treat cisplatin-induced hearing loss (CIHL). Sodium thiosulfate effectively inactivates cisplatin through covalent binding and may provide protection against cisplatin-induced ototoxicity. DB-020 is being developed as a novel formulation of sodium thiosulfate pentahydrate in 1% sodium hyaluronate for intratympanic injection (IT), enabling the delivery of high concentrations of thiosulfate into the cochlea prior to cisplatin administration. In the DB-020-002 phase 1a single-ascending dose study, healthy volunteers were enrolled into 5 cohorts to receive different doses of DB-020 via IT injection. Cohorts 1-4 received unilateral injections while Cohort 5 received bilateral injections. Plasma thiosulfate pharmacokinetics was measured, and safety and audiometric data were collected throughout the study. This study has demonstrated that intratympanic administration of DB-020 results in nominal systemic increases in thiosulfate levels, hence it should not compromise cisplatin anti-tumor efficacy. Furthermore, DB-020 was safe and well tolerated with most adverse events reported as transient, of mild-to-moderate severity and related to the IT administration procedure. These results support the design and execution of the ongoing proof-of-concept study, DB-020-002, to assess otoprotection using DB-020 in cancer patients receiving cisplatin without negatively impacting cisplatin anti-tumor efficacy.


Antineoplastic Agents/administration & dosage , Hearing Loss/prevention & control , Thiosulfates/administration & dosage , Adult , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cisplatin/pharmacokinetics , Double-Blind Method , Female , Healthy Volunteers , Hearing Loss/chemically induced , Humans , Injection, Intratympanic , Male , Middle Aged , Neoplasms/drug therapy , Neoplasms/metabolism , Thiosulfates/adverse effects , Thiosulfates/blood , Thiosulfates/pharmacokinetics , Young Adult
7.
Biosci Biotechnol Biochem ; 83(1): 114-122, 2019 Jan.
Article En | MEDLINE | ID: mdl-30200826

The present study describes the hair growth-promoting effects of sodium thiosulfate (STS), a widely used compound, in mice. STS accelerated hair growth in the "telogen model", suggesting that it stimulates telogen hair follicles to reenter the anagen phase of hair growth. In the same model, STS potentiated hair growth in an additive manner with minoxidil (MXD), a drug used for the treatment of androgenic alopecia. Furthermore, in the "anagen model", STS promoted hair growth, probably by promoting hair follicle proliferation. Since STS elevated the skin surface temperature, its hair growth-promoting activity may be partly due to vasorelaxation, similar to MXD. In addition, STS is known to generate a gaseous mediator, H2S, which has vasorelaxation and anti-inflammatory/anti-oxidative stress activities. Therefore, STS and/or provisionally its metabolite, H2S, may aid the hair growth process. Collectively, these results suggest that salts of thiosulfate may represent a novel and beneficial remedy for hair loss.


Hair Follicle/drug effects , Hair Follicle/growth & development , Models, Animal , Thiosulfates/pharmacology , Alopecia/drug therapy , Animals , Drug Synergism , Gene Expression Regulation/drug effects , Humans , Male , Mice, Inbred C3H , Minoxidil/administration & dosage , Minoxidil/adverse effects , Minoxidil/pharmacology , Models, Biological , Skin Temperature/drug effects , Sulfurtransferases/genetics , Sulfurtransferases/metabolism , Thiosulfates/administration & dosage , Thiosulfates/adverse effects
8.
N Engl J Med ; 378(25): 2376-2385, 2018 Jun 21.
Article En | MEDLINE | ID: mdl-29924955

BACKGROUND: Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival. METHODS: We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses. The primary end point was the absolute hearing threshold, as measured by pure-tone audiometry, at a minimum age of 3.5 years. Hearing loss was assessed according to the Brock grade (on a scale from 0 to 4, with higher grades indicating greater hearing loss). The main secondary end points were overall survival and event-free survival at 3 years. RESULTS: A total of 109 children were randomly assigned to receive cisplatin plus sodium thiosulfate (57 children) or cisplatin alone (52) and could be evaluated. Sodium thiosulfate was associated with few high-grade toxic effects. The absolute hearing threshold was assessed in 101 children. Hearing loss of grade 1 or higher occurred in 18 of 55 children (33%) in the cisplatin-sodium thiosulfate group, as compared with 29 of 46 (63%) in the cisplatin-alone group, indicating a 48% lower incidence of hearing loss in the cisplatin-sodium thiosulfate group (relative risk, 0.52; 95% confidence interval [CI], 0.33 to 0.81; P=0.002). At a median of 52 months of follow-up, the 3-year rates of event-free survival were 82% (95% CI, 69 to 90) in the cisplatin-sodium thiosulfate group and 79% (95% CI, 65 to 88) in the cisplatin-alone group, and the 3-year rates of overall survival were 98% (95% CI, 88 to 100) and 92% (95% CI, 81 to 97), respectively. CONCLUSIONS: The addition of sodium thiosulfate, administered 6 hours after cisplatin chemotherapy, resulted in a lower incidence of cisplatin-induced hearing loss among children with standard-risk hepatoblastoma, without jeopardizing overall or event-free survival. (Funded by Cancer Research UK and others; SIOPEL 6 ClinicalTrials.gov number, NCT00652132 ; EudraCT number, 2007-002402-21 .).


Cisplatin/adverse effects , Hearing Loss/prevention & control , Hepatoblastoma/drug therapy , Liver Neoplasms/drug therapy , Thiosulfates/therapeutic use , Adolescent , Child , Child, Preschool , Cisplatin/administration & dosage , Doxorubicin/administration & dosage , Drug Therapy, Combination , Female , Follow-Up Studies , Glomerular Filtration Rate , Hearing Loss/chemically induced , Hepatoblastoma/mortality , Humans , Incidence , Infant , Liver Neoplasms/mortality , Male , Single-Blind Method , Survival Analysis , Thiosulfates/administration & dosage , Thiosulfates/adverse effects
9.
Nephron ; 139(3): 219-227, 2018.
Article En | MEDLINE | ID: mdl-29587288

BACKGROUND: Arterial stiffness (AS) and vascular calcification are significantly related to a high cardiovascular mortality risk in hemodialysis (HD) patients. Intravenous sodium thiosulfate (IV STS) can prevent and delay the vascular calcification progression in uremic states; however, the STS effect on AS has not been assessed. This study aimed to evaluate the STS efficacy on vascular calcification and AS in HD patients. METHODS: Fifty HD patients with abnormal AS, as measured via the cardio-ankle vascular index (CAVI ≥8), were prospectively randomized to open-label 12.5 g IV STS during the last HD hour twice weekly for 6 months (n = 24) or the usual care (control group; n = 26). Patients and treating physicians were not blinded. The CAVI, coronary artery calcification (CAC) score, hemodynamics, and biochemical parameters were measured at the baseline and at 3 and 6 months. RESULTS: All the baseline parameters were comparable. The IV STS significantly reduced the CAVI when compared to the control group (mean CAVI difference = -0.53; 95% CI -1.00 to -0.06; p = 0.03). A significant CAVI improvement was seen in those patients without diabetes mellitus. The natural logarithm of the CAC volume score was significantly increased in the control group. The high sensitivity C-reactive protein level was slightly lowered in the IV STS group (not significant). CONCLUSION: The intradialytic STS treatment significantly reduced the AS, as measured by the CAVI, and stabilized the vascular calcification in the HD patients. STS may be a novel therapeutic strategy for delaying and treating the structural and functional vascular wall abnormalities in HD patients.


Kidney Failure, Chronic/drug therapy , Kidney Failure, Chronic/therapy , Renal Dialysis , Thiosulfates/therapeutic use , Vascular Stiffness/drug effects , Adult , Aged , Ankle Brachial Index , C-Reactive Protein/metabolism , Combined Modality Therapy , Coronary Artery Disease/etiology , Coronary Artery Disease/physiopathology , Female , Hemodynamics , Humans , Kidney Failure, Chronic/physiopathology , Male , Middle Aged , Prospective Studies , Thiosulfates/adverse effects , Tomography, X-Ray Computed , Treatment Outcome , Vascular Calcification/drug therapy
10.
Nephrology (Carlton) ; 23(7): 669-675, 2018 Jul.
Article En | MEDLINE | ID: mdl-28603903

AIM: Calciphylaxis is a severe complication of advanced chronic kidney disease (CKD). Sodium thiosulphate (STS), an antioxidant and calcium chelating agent, has been used for the treatment of calciphylaxis. However, its efficacy and safety have not been systematically analysed and evaluated. METHODS: MEDLINE, EMBASE, and the Cochrane Library database were systematically searched for case report or cases series on use of STS for calciphylaxis published between July 1974 and October 2016. We extracted data on clinical characteristics, laboratory tests result and medication use. The effective treatment was defined as improvement in skin lesion cicatrisation or pain relief without death. Non-responding effects were defined as stable skin lesions without remission or exacerbation of the disease in patients who remained alive. All-cause mortality after STS treatment was defined as death due to exacerbations of calciphylaxis or other complications of advanced CKD. We compared the baseline parameters of the patients as well as the efficacy and mortality of the STS therapy between case report and multi-case reports. Statistical analyses were performed using SPSS 19. RESULTS: A total of 83 papers were screened, 45 of them (n = 358) met the inclusion criteria, including 36 case reports (n = 64) and nine multi-case reports (n = 294). The mean age of the patients with calciphylaxis was 58 ± 14 years (range 26-91 years). They were female predominant, accounting for 74.1%. Among the patients with calciphylaxis, 96.1% patients were on dialysis with median dialysis vintage of 44.5 months (range 24-84 months). STS was effective in 70.1% of patients, 37.6% patients died. The proportion of patients with sepsis was higher among those who received intravenous STS. There was no significant difference in efficacy between the different STS administration methods (P = 0.19). CONCLUSION: Although the study was unable to assess the efficacy of sodium thiosulphate alone in the treatment of calciphylaxis, it still reveals a promising role of STS as an effective therapy for calciphylaxis. Further prospective studies to define the optimal therapy for calciphylaxis are needed.


Antioxidants/therapeutic use , Calciphylaxis/drug therapy , Calcium Chelating Agents/therapeutic use , Renal Insufficiency, Chronic/complications , Thiosulfates/therapeutic use , Adult , Aged , Aged, 80 and over , Antioxidants/adverse effects , Calciphylaxis/diagnosis , Calciphylaxis/etiology , Calcium Chelating Agents/adverse effects , Female , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/diagnosis , Thiosulfates/adverse effects , Treatment Outcome
12.
Lancet Oncol ; 18(1): 63-74, 2017 01.
Article En | MEDLINE | ID: mdl-27914822

BACKGROUND: Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. METHODS: ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada. Eligible participants aged 1-18 years with newly diagnosed cancer and normal audiometry were randomly assigned (1:1) to receive sodium thiosulfate or observation (control group) in addition to their planned cisplatin-containing chemotherapy regimen, using permuted blocks of four. Randomisation was initially stratified by age and duration of cisplatin infusion. Stratification by previous cranial irradiation was added later as a protocol amendment. The allocation sequence was computer-generated centrally and concealed to all personnel. Participants received sodium thiosulfate 16 g/m2 intravenously 6 h after each cisplatin dose or observation. The primary endpoint was incidence of hearing loss 4 weeks after final cisplatin dose. Hearing was measured using standard audiometry and reviewed centrally by audiologists masked to allocation using American Speech-Language-Hearing Association criteria but treatment was not masked for participants or clinicians. Analysis of the primary endpoint was by modified intention to treat, which included all randomly assigned patients irrespective of treatment received but restricted to those assessable for hearing loss. Enrolment is complete and this report represents the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00716976. FINDINGS: Between June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28·6%; 95% CI 16·6-43·3) participants in the sodium thiosulfate group compared with 31 (56·4%; 42·3-69·7) in the control group (p=0·00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0·31, 95% CI 0·13-0·73; p=0·0036). The most common grade 3-4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 [66%] of 177 participant cycles in the sodium thiosulfate group vs 145 [65%] of 223 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 [17%] of 147 vs 22 [12%] of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants. INTERPRETATION: Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies. FUNDING: US National Cancer Institute.


Antineoplastic Agents/adverse effects , Antioxidants/adverse effects , Cisplatin/adverse effects , Hearing Loss/chemically induced , Neoplasms/drug therapy , Thiosulfates/adverse effects , Adolescent , Child , Child, Preschool , Drug Therapy, Combination , Female , Follow-Up Studies , Hearing Loss/epidemiology , Humans , Incidence , Infant , Male , Neoplasm Staging , Neoplasms/pathology , Prognosis , Survival Rate , United States/epidemiology
13.
J Intensive Care Med ; 32(9): 547-553, 2017 Oct.
Article En | MEDLINE | ID: mdl-27435907

PURPOSE: This study evaluated thiocyanate concentrations and factors associated with thiocyanate accumulation in intensive care unit patients receiving nitroprusside with and without sodium thiosulfate coadministration. MATERIALS AND METHODS: This retrospective study evaluated critically ill adults who received nitroprusside infusions and had at least one thiocyanate concentration. Patients with thiocyanate accumulation (concentrations ≥30 µg/mL) were compared to patients without accumulation. Factors associated with accumulation were determined by Spearman correlation and multivariate regression. RESULTS: Thiocyanate concentrations (n = 192) were obtained from 87 patients. Fourteen of the 87 (16%) patients experienced thiocyanate accumulation with a mean (SD) thiocyanate concentration of 44 ± 11 µg/mL. Patients with accumulation had received greater cumulative nitroprusside doses (28 vs 8.2 mg/kg, P < .01), greater cumulative sodium thiosulfate doses (16.8 vs 10.1 mg/kg, P < .01), and longer infusion durations (10.9 vs 6.0 days, P < .01), compared to patients without accumulation. Sodium thiosulfate coadministration resulted in greater thiocyanate concentrations (22.8 ± 16.7 vs 16.8 ± 14.9 µg/mL, P = .01), despite utilization of lower cumulative nitroprusside doses (10.2 vs 14.6 mg/kg, P = .03). Cumulative nitroprusside dose ( r2 .44, P < .001) and cumulative sodium thiosulfate dose ( r2 .32, P < .001) demonstrated a significant correlation with measured thiocyanate concentrations. Thiocyanate accumulation was independently associated with cumulative nitroprusside dose in mg/kg (regression coefficient 0.75, 95% CI 0.63-0.89; P < .01). No clinically significant adverse effects of cyanide or thiocyanate toxicity were observed. CONCLUSIONS: Cumulative nitroprusside dose was independently associated with thiocyanate accumulation. Despite elevated thiocyanate levels in 16% of patients, there was no clinical evidence of cyanide or thiocyanate toxicity. Routine monitoring of thiocyanate concentrations appears most warranted in patients receiving higher cumulative doses of nitroprusside.


Antidotes/adverse effects , Nitroprusside/adverse effects , Thiocyanates/blood , Thiosulfates/adverse effects , Vasodilator Agents/adverse effects , Adult , Aged , Antidotes/administration & dosage , Critical Care/methods , Critical Illness/therapy , Drug Monitoring , Drug Therapy, Combination , Female , Humans , Infusions, Intravenous , Intensive Care Units , Male , Middle Aged , Multivariate Analysis , Nitroprusside/administration & dosage , Regression Analysis , Retrospective Studies , Statistics, Nonparametric , Thiosulfates/administration & dosage , Vasodilator Agents/administration & dosage
14.
J Clin Endocrinol Metab ; 101(7): 2810-5, 2016 07.
Article En | MEDLINE | ID: mdl-27163355

CONTEXT: Hyperphosphatemic familial tumoral calcinosis (HFTC) and hyperphosphatemia hyperostosis syndrome (HHS) are rare diseases characterized by hyperphosphatemia and ectopic calcifications or recurrent episodes of diaphysitis. In the setting of metabolic or inflammatory diseases, recent data suggest that systemic administration of sodium thiosulfate (STS) could be effective in the treatment of ectopic calcifications but may also be poorly tolerated (digestive symptoms, metabolic acidosis). Our group developed a topical formulation of STS to treat ectopic calcifications locally, therefore limiting patient exposure to the drug and its adverse effects. OBJECTIVE: We aimed at describing efficacy and tolerance for a topical formulation of STS in treated patients. DESIGN: We performed a retrospective study wherein clinical, radiological, and biological data before and after the application of the topical STS treatment were collected and analyzed. PATIENTS OR OTHER PARTICIPANTS: Three patients admitted to 3 different hospitals with an ectopic calcification secondary to HFTC or HHS were treated with topical STS. INTERVENTION: The topical STS was applied daily by the patients. RESULTS: A significant clinical and radiological decrease of ectopic calcifications was observed after at least 5 months of treatment. The STS treatment was well tolerated and no clinical or biological side effects were observed. CONCLUSION: Topical STS appears to be a promising treatment for ectopic calcifications secondary to HFTC or HHS.


Calcinosis/drug therapy , Hyperostosis, Cortical, Congenital/drug therapy , Hyperphosphatemia/drug therapy , Thiosulfates/administration & dosage , Thiosulfates/adverse effects , Administration, Topical , Adult , Calcinosis/diagnosis , Child , Female , Humans , Hyperostosis, Cortical, Congenital/diagnosis , Hyperphosphatemia/diagnosis , Male , Prognosis , Retrospective Studies , Treatment Outcome
17.
J Cutan Med Surg ; 18(5): 356-60, 2014 Oct.
Article En | MEDLINE | ID: mdl-25186999

UNLABELLED: AbstractBackground:Calciphylaxis is a life-threatening condition traditionally observed in patients with end-stage renal disease. Cases of nonuremic calciphylaxis have also been reported, but data on this rare condition are mainly empirical. OBJECTIVES: To present a case of severe nonuremic calciphylaxis treated with intravenous sodium thiosulfate (IV STS) and to assess the implications of this treatment. METHODS: Case report and review of the literature. RESULTS: A nonuremic patient diagnosed with distal calciphylaxis was started on IV STS after a 12-month nonresponse to conventional therapy. On week 12, the patient requested palliative care, given her many side effects (transient severe nausea and significant electrolyte imbalance). Pain subsided after 14 weeks, and complete wound healing was observed after 6 months. CONCLUSION: Based on this case report, IV STS can improve refractory calciphylaxis in nonuremic patients. However, literature on the subject remains scarce. Careful monitoring for adverse transient side effects is advised.


Calciphylaxis/drug therapy , Chelating Agents/adverse effects , Thiosulfates/adverse effects , Water-Electrolyte Imbalance/chemically induced , Administration, Intravenous , Calciphylaxis/complications , Chelating Agents/administration & dosage , Female , Humans , Leg Ulcer/etiology , Middle Aged , Nausea/chemically induced , Nausea/drug therapy , Retreatment , Thiosulfates/administration & dosage , Water-Electrolyte Imbalance/therapy
18.
Ear Hear ; 35(6): e243-7, 2014.
Article En | MEDLINE | ID: mdl-25127324

OBJECTIVES: Ototoxic hearing loss associated with intravenous or intra-arterial administration of cisplatin is well documented. However, there is limited data regarding the ototoxic effect of cisplatin when perfused into the abdominal cavity using hyperthermic intraperitoneal chemotherapy (HIPEC). The purpose of this study is to assess and describe ototoxicity in patients treated with HIPEC with cisplatin and sodium thiosulfate for peritoneal surface malignancies. DESIGN: We performed a retrospective chart review (2007-2012) of patients treated for advanced peritoneal malignancies at a tertiary care center using HIPEC with cisplatin and sodium thiosulfate infusion. Thirteen patients (12 males, 1 female) met study criteria. Audiometric thresholds were compared before and after treatment. A 20 dB loss at any single frequency, 10 dB decrease at any two adjacent frequencies, or loss of response at three consecutive test frequencies defined a significant ototoxic change (). RESULTS: Despite minimal hearing change in six patients, none of the 13 patients in our study exhibited a significant ototoxic change in hearing sensitivity post HIPEC with cisplatin at any test interval in any test frequency. CONCLUSIONS: Our findings represent the first objective assessment of ototoxic effect after HIPEC with cisplatin and sodium thiosulfate infusion. Our results suggest that peritoneal perfusion of cisplatin with intravenous perfusion of sodium thiosulfate is not associated with ototoxic changes in hearing sensitivity. Further investigation of the administration and systemic mechanism of absorption of sodium thiosulfate as a potential protection against cisplatin ototoxicity is needed to confirm these findings.


Antineoplastic Agents/adverse effects , Antioxidants/adverse effects , Cisplatin/adverse effects , Hearing Loss, Sensorineural/chemically induced , Peritoneal Neoplasms/therapy , Thiosulfates/adverse effects , Adolescent , Adult , Audiometry, Pure-Tone , Auditory Threshold , Child , Female , Humans , Hyperthermia, Induced/methods , Infusions, Parenteral , Male , Retrospective Studies , Young Adult
19.
Int J Artif Organs ; 37(4): 308-14, 2014 Apr.
Article En | MEDLINE | ID: mdl-24811185

BACKGROUND: Cardiovascular calcification (CVC) in hemodialysis patients (HDP) causes cardiovascular pathology. Up until now very few drugs and therapeutic interventions have been able to reduce cardiovascular calcium deposits in hemodialysis patients and the process requires more than a year. Our idea in this study was to test 2 calcium binders--sodium thiosulfate (STS) and dinatrium ethylene diamine tetraacetic acid (DNEDTA)--for prevention and treatment of cardiovascular calcification of hemodialysis patients, using both substances not as an intravenous infusion but by adding them to the liquid bicarbonate part of the dialysis fluid. MATERIAL AND METHODS: 6 HDPs were treated with sodium thiosulphate (STS), 6 with dinatrium ethylene diamine tetraacetic acid (DNEDTA), and 6 patients served as controls. Electrolytes, liver function, markers of inflammation, oxidative stress, bone metabolism, spiral computed tomography (SCT) of coronary CVC and bone densitometry were performed twice (start and end of the study). RESULTS: Starting blood parameters were similar to the end (STS group). No toxic or side effects from STS were observed. Initially in the DNEDTA group all the patients had vomiting so we excluded DNEDTA from the study. SCT found a significant reduction of calcification in 4 patients (STS group) and retardation in 2 patients comparatively to controls. CONCLUSIONS: The first results are hopeful, but the number of the patients was small, so we are enlarging the enrollment in the expectation of corroborating our results soon.


Calcium Chelating Agents/therapeutic use , Coronary Artery Disease/prevention & control , Hemodialysis Solutions/therapeutic use , Renal Dialysis/methods , Thiosulfates/therapeutic use , Vascular Calcification/prevention & control , Biomarkers/blood , Calcium Chelating Agents/adverse effects , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Coronary Artery Disease/etiology , Edetic Acid/therapeutic use , Hemodialysis Solutions/adverse effects , Humans , Pilot Projects , Renal Dialysis/adverse effects , Thiosulfates/adverse effects , Time Factors , Treatment Outcome , Vascular Calcification/blood , Vascular Calcification/diagnosis , Vascular Calcification/etiology
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