Antidote For Cyanide Poisoning Research Articles

Evaluation of Protective Potential of Aqueous Seed extract of Ripe Fruits of Carica papaya on Cyanide Induced Kidney Damage in Male Wister Rats

This study aimed to evaluate the protective potential of aqueous seed extract of ripe Carica papaya fruits on cyanide induced kidney damage in male Wister rats using 24 male rats divided into five groups. The animals were sacrificed at the end of the experimental period and serum and kidney were harvested for biochemical and histological analysis following standard procedures. Estimation of kidney function markers such as creatinine and urea and assessment of electrolytes of toxicological relevance; sodium ion, potassium ion, bicarbonate ion and chloride ion were carried out. The study revealed that cyanide stimulated alterations in kidney function makers: urea, creatinine and serum electrolytes. The result indicated that aqueous seed extract of Carica papaya fruits significantly increase Urea, creatinine, Cl-, HCO3-, K+ and Na+ activities in the rats induced with cyanide when compared with the positive control. However, the concentrations were significantly decreased in the treated groups when compared with the groups induced with cyanide. Histological analysis showed cyanide induced structural distortions of the kidney tissues. Treatment with Carica papaya seed extract was able to mitigate these damages. This study indicates that aqueous seed extract of ripe fruits of Carica papaya possesses nephro-protective properties and can be used as an antidote for cyanide poisoning.

In Vitro Characterization of a Threonine-Ligated Molybdenyl-Sulfide Cluster as a Putative Cyanide Poisoning Antidote; Intracellular Distribution, Effects on Organic Osmolyte Homeostasis, and Induction of Cell Death.

Binuclear molybdenum sulfur complexes are effective for the catalytic conversion of cyanide into thiocyanate. The complexes themselves exhibit low toxicity and high aqueous solubility, which render them suitable as antidotes for cyanide poisoning. The binuclear molybdenum sulfur complex [(thr)Mo2O2(μ-S)2(S2)]- (thr - threonine) was subjected to biological studies to evaluate its cellular accumulation and mechanism of action. The cellular uptake and intracellular distribution in human alveolar (A549) cells, quantified by inductively coupled plasma mass spectrometry (ICP-MS) and cell fractionation methods, revealed the presence of the compound in cytosol, nucleus, and mitochondria. The complex exhibited limited binding to DNA, and using the expression of specific protein markers for cell fate indicated no effect on the expression of stress-sensitive channel components involved in cell volume regulation, weak inhibition of cell proliferation, no increase in apoptosis, and even a reduction in autophagy. The complex is anionic, and the sodium complex had higher solubility compared to the potassium. As the molybdenum complex possibly enters the mitochondria, it is considered as a promising remedy to limit mitochondrial cyanide poisoning following, e.g., smoke inhalation injuries.

Liposomal methemoglobin as a potent antidote for hydrogen sulfide poisoning

Hydrogen sulfide (H2S) induces acute and lethal toxicity at high concentrations. However, no specific antidotes for H2S poisoning have been approved. Liposomal methemoglobin (metHb@Lipo) was developed as an antidote for cyanide poisoning. As the toxic mechanism of H2S poisoning is the same as that of cyanide poisoning, metHb@Lipo could potentially be used as an antidote for H2S poisoning. In this study, we evaluated the antidotal efficacy of metHb@Lipo against H2S poisoning. Stopped-flow rapid-scan spectrophotometry clearly showed that metHb@Lipo scavenged H2S rapidly. Additionally, metHb@Lipo showed cytoprotective effects against H2S exposure in H9c2 cells by maintaining mitochondrial function. MetHb@Lipo treatment also improved the survival rate after H2S exposure in vivo, with the maintenance of cytochrome c oxidase activity and suppression of metabolic acidosis. Moreover, metHb@Lipo therapy maintained significant antidotal efficacy even after 1-year-storage at 4–37 °C. In conclusion, metHb@Lipo is a candidate antidote for H2S poisoning.

Long-term pharmaceutical stability of liposome-encapsulated methemoglobin as an antidote for cyanide poisoning

Liposome-encapsulated methemoglobin (metHb@Lipo) has been developed as a novel antidote for cyanide poisoning. Antidotes for lethal acute poisoning should be capable of being easily stored as ready-to-use formulations without temperature restrictions. Here, we investigated the pharmaceutical stability of the metHb@Lipo suspension after one-year storage as a ready-to-use formulation at 4 °C, room temperature (23–28 °C) and 37 °C. The liposomal integrity of metHb@Lipo was observed after one year of storage at all storage temperatures with no physicochemical change or methemoglobin leakage outside the liposome. Furthermore, the encapsulated methemoglobin remained intact without aggregation, fragmentation, denaturation, or dissociation of heme. Fresh and stored metHb@Lipo were equivalent in their binding affinity against cyanide. Moreover, all one-year stored metHb@Lipo suspensions improved the mortality rates of lethal cyanide poisoning mice comparable to fresh metHb@Lipo suspension. Additionally, all stored metHb@Lipo suspensions preserved high biocompatibility, including blood compatibility and the lack of organ toxicity. In conclusion, the metHb@Lipo suspension was a pharmaceutically stable antidote for cyanide poisoning for at least one year without any temperature restrictions.

Hydroxocobalamin interference in routine laboratory tests: Development of a protocol for identifying samples and reporting results from patients treated with CyanokitTM

ObjectivesHydroxocobalamin (OHCob) is an antidote for cyanide poisoning in patients rescued from house fires and is known to cause interference with certain laboratory tests. Consensus is lacking on the extent of this interference and on how to handle these samples. The objectives of this study were to characterize OHCob interference across a wide range of laboratory tests and to develop protocols for identifying and reporting these samples. Designs & methodsPatient plasma samples (n = 5) were spiked with OHCob (1.5 mg/mL) and compared to controls without this drug. A series of analytes were measured using chemistry, urinalysis, coagulation, hematology, and blood gas instruments. Dose-response testing was performed on a subset of assays that showed interferences ≥10%. ResultsOf the 77 analytes evaluated, 27 (35%) showed interference from OHCob, with chemistry and coagulation analytes showing the greatest effects. Of those affected, 22 analytes had a positive interference, whereas 5 analytes had negative interference. Dose-response studies showed dose-dependent increases and/or decreases consistent with initial spiking studies. Although red in colour, plasma samples with OHCob did not trigger hemolysis index flags, necessitating a special sample identification and reporting protocol. ConclusionOHCob had significant effects on several analytes across different instruments. These findings led to the development of special sample handling and reporting protocols to identify OHCob samples and ensure only accurate results are released. It is vital for emergency departments to document and notify their laboratories whenever blood samples from these patients are drawn.

Appropriate Utilization and Stocking of Antidotes in Qatar Public Hospitals

Background: There are a few studies that evaluate preparedness and availability of antidotes in the emergency setting and none have been conducted in Qatar. Published studies show that timely availability of antidotes in the emergency department setting is a common issue. To address this, we conducted a study to evaluate antidote stocking and utilization in Qatar hospital pharmacies and emergency departments. Methods: In order to evaluate the appropriate use and timely administration of antidotes, research assistants prospectively collected data on ED patients. All ED patients who received any key antidote over the 6-month study period were identified through both ED and pharmacy records. In order to evaluate the stocking of the 31 most important antidotes in our main public hospitals, a survey assessing the stocking of these key antidotes was sent to the four general hospitals in Qatar, to determine their availability and whether they are stocked in the ED or only in the main pharmacy. Results: Poison exposure was evaluated in 471 cases. Antidotes were given within 30 minutes in 73% of cases, which included atropine, calcium, dextrose, flumazenil, naloxone, pralidoxime, sodium bicarbonate, thiamine, vitamin K and scorpion and snake antivenoms. Administration occurred later than 60 minutes in 2% of cases, exclusively with N-acetylcysteine and activated charcoal. Atropine, calcium, dextrose, naloxone, pralidoxime (2-PAM), sodium bicarbonate, and anti-venoms were clinically indicated 92% of the times they were ordered. N-acetylcysteine was indicated in only 51.5% of administrations. Significant variation in antidote stocking existed between hospitals, and there was no stocked hydroxocobalamin as antidotes for cyanide poisoning or fomepizole for toxic alcohol poisoning. Conclusion: Antidote stocking varied significantly between hospitals, and antidotes necessary for cyanide and toxic alcohol poisoning were deficient in all public hospitals. The implication of this research indicates the need for the development of national guidelines to standardize the stocking and administration protocols of the antidotes among the country’s public hospitals.

Calciphylaxis: Early Detection and Off-Label Treatment With Sodium Thiosulfate

Calciphylaxis or calcific uremic arteriolopathy (CUA) is a rare disorder of calcium and phosphate metabolism most often manifesting in end-stage renal disease (ESRD) patients. The typical clinical picture is that of a necrotic cutaneous ulceration with focal or diffuse distribution, most often manifesting on the lower extremities. We report a 49-year-old Caucasian male with ESRD on hemodialysis who presented to the emergency department with complaints of lower extremity pain and multiple cutaneous necrotic lesions on his lower extremities. Patient reports seeking assistance from several medical providers over a 3-month period. Upon admission and further evaluation, a diagnosis of calciphylaxis was made clinically and confirmed by a skin biopsy. Sodium thiosulfate was initiated and the clinical picture improved significantly. Sodium thiosulfate is traditionally used as an antidote for cyanide poisoning, and it has demonstrated beneficial outcomes in most patients afflicted with CUA. The rationale behind sodium thiosulfate therapy in CUA is its role in chelating calcium into calcium thiosulfate, which increases its solubility leading to improved renal clearance. It is essential to raise awareness amongst physicians and medical practitioners alike, as early recognition and initiation of appropriate treatment can improve the patients’ quality of life and more importantly, decrease mortality. World J Nephrol Urol. 2017;6(3-4):25-28 doi: https://doi.org/10.14740/wjnu298e

Effects of <i>Alium cepa Linn</i> on rhodanese activities and half-life of cyanide in the blood

Rhodanese is the major detoxifying enzyme for cyanide and requires sulphur for its action. Allium cepa (Onion) is rich in organosulphur which may serve as an antidote for cyanide poisoning by supplying sulphur to the enzyme rhodanese. The possible effects of Allium cepa on rhodanese activity during cyanide toxicity was investigated in male Wistar rats. Sixty Wistar rats (150-180 g) were divided into ten groups of six rats each. The first six groups were used for in vivo rhodanese activities evaluation after treatments orally with either KCN (7 mg/kg bwt/day KCN), KCN+300 mg Methanol Extract of Allium cepa (MEAC)/kg bwt/day, KCN+600 mg MEAC/kg bwt/day, KCN+ 600 mg sodium thiosulphate (Na2S2O3) /kg bwt/day or 600 mg MEAC /kg bwt/day respectively. The last four groups were used for the evaluation of half-life of KCN after treatment orally with distilled water (control), 600 mg MEAC/kg bwt/day, 600 mg Na2S2O3/kg bwt/day and raw onion adlibitum respectively for two weeks before intravenous injection of KCN. In vitro rhodanese activity was determined using liver homogenate. Results of the in vivo study showed liver rhodanese activity was significantly higher (p<0.05) in the cyanide only group and in the cyanide + Na2S2O3 group when compared with the control group, but administration of MEAC in the cyanide treated group did not enhance the activities of rhodanese. The results of the in vitro study showed that rhodanese activity was more enhanced in the presence of essential oil of onion and Na 2 S 2 O 3 . The half-life of KCN was significantly lower (p<0.05) with consumption of raw onion when compared with control. The results suggest that Allium cepa enhance cyanide detoxification by enhancing rhodanese enzyme activities. This effect is more pronounced with the essential oil of onion.

Early administration of isosorbide dinitrate improves survival of cyanide-poisoned rabbits

Context. More effective, rapidly delivered, safer antidotes are needed for cyanide poisoning. Previous study has demonstrated a beneficial effect of isosorbide dinitrate on the survival of cyanide-poisoned mice. Objective. To evaluate the effectiveness of isosorbide dinitrate compared with that of sodium nitrite in cyanide poisoning. Materials and methods. A comparative animal study was performed using 18 rabbits, randomized into 3 study groups. Animals were poisoned intravenously with potassium cyanide (1 mg/kg). The first group was not given any further treatment. The second and third groups were treated intravenously 1 min after poisoning with sodium nitrite (6 mg/kg) and isosorbide dinitrate (50 μg/kg), respectively. The primary outcome was short-term survival of up to 30 min. Secondary outcomes included time to death, a clinical score, mean blood pressure, pulse, blood pH, and lactate and methemoglobin levels. Results. Rabbits treated with isosorbide dinitrate or sodium nitrite survived while only one untreated rabbit survived. Median time to death of the 5 poisoned and untreated animals was 10 min. All the animals collapsed soon after poisoning, exhibiting rapidly disturbed vital signs and developed lactic metabolic acidosis; average peak blood lactate levels were 15.5–19.1 mmol/L at 10 min after poisoning. The treated animals improved gradually with practically full recovery of the clinical scores, vital signs, and blood gas levels. Sodium nitrite administration raised methemoglobin to an average peak of 7.9%, while isosorbide dinitrate did not change methemoglobin levels. Conclusion. Early administration of isosorbide dinitrate improved the short-term survival of cyanide-poisoned rabbits. Isosorbide dinitrate shows potential as an antidote for cyanide poisoning and may exert its effect using a nitric-oxide-dependent mechanism.

PharmGKB summary

The many uses of methylene blue Methylene blue (methylthioninium chloride) is a ‘jack of all trades’ with a litany of clinical uses. In vivo, it is indicated for use as a therapy for drug-induced methemoglobinemia [1-3], can be used for the treatment of infections, pathologies, or poisoning, and as a dye for diagnostics. It is also commonly used as a dye in vitro – for example, as a component in staining of cells, tissues, DNA, parasites, and bacteria [4-6]. In the 1890s, Ehrlich demonstrated its use to target the malarial parasite, and more recently it has been reinvestigated for inclusion in antimalarial regimens in the wake of parasite drug resistance [7-9]. Further examples of its clinical use include treatment of ifosfamide-induced neurotoxicity (although treatment has been reported ineffective), an antidote for cyanide poisoning, visualization of fallopian tubes or ruptured membranes, a marker of tumors, and even as a potential therapy for septic shock and ischemic brain injury [5,8,10-18]. In phase II clinical trials, a modified version of methylene blue is reported to slow cognitive decline in mild–moderate Alzheimer’s disease patients compared to placebo, and phase III trials are planned, although these results remain unpublished [19]. The mechanism of action is unclear – possibly by preventing tau protein aggregation or increasing amyloid-β clearance by enhancing proteasome activities [19,20]. As a photodynamic therapy, methylene blue could be used to treat psoriasis, West Nile virus infection, AIDS-related Kaposi’s sarcoma, antibiotic-resistant bacterial strains and decontaminate blood before transfusion [5,21-25]. Methylene blue has also contributed to drug development, forming the structural chemical basis of other therapeutic drugs, including the antimalarial drug, chloroquine; the antihistamine, promethazine; and the antipsychotic, chlorpromazine [5]. Acknowledging the many uses of methylene blue, this article focuses on the pharmacodynamics of methylene blue in the context of methemoglobinemia treatment and the pathways surrounding this, due to known pharmacogenetic associations that relate to these pathways.

Rapid determination of isoamyl nitrite in pharmaceutical preparations by flow injection analysis with on‐line UV irradiation and luminol chemiluminescence detection

Isoamyl nitrite is used as a therapeutic reagent for cardiac angina and as an antidote for cyanide poisoning, but it is abused because of its euphoric properties. Therefore, a method to determine isoamyl nitrite is required in many fields, including pharmaceutical and forensic studies. In this study, a simple, rapid and sensitive method for the determination of isoamyl nitrite was developed using a flow injection analysis system equipped with a chemiluminescence detector and on-line photoreactor. This method is based on on-line ultraviolet irradiation of isoamyl nitrite and subsequent luminol chemiluminescence detection without the addition of an oxidant. A linear standard curve was obtained up to 1.0 μM of isoamyl nitrite with a detection limit (blank + 3SD) of 0.03 μM. The method was successfully applied to determine isoamyl nitrite content in pharmaceutical preparations.

Development of a Treatment Agent for Mass Casualty Smoke-Cyanide Exposure

Smoke inhalation is the major cause of death in fire victims. Combined cyanide and carbon monoxide poisoning is frequent in smoke inhalation victims, and mortality correlates more closely with cyanide levels than carbon monoxide exposure levels. There is currently no available treatment for mass casualty cyanide exposure, since treatment of individual victims requires administration of intravenous antidotes, and some antidote agents are contraindicated in smoke inhalation. We are developing a novel cyanide antidote, cobinamide, which could be administered intravenously or intramuscularly in mass casualty cyanide poisoning scenarios. Because cyanide antidotes cannot be tested for efficacy in humans, animal studies must be performed to demonstrate effectiveness of this agent in combined smoke-cyanide inhalation for FDA approval.METHODS: Six ventilator-supported New Zealand white rabbits were exposed to cold smoke breaths until toxic carbon monoxide levels were achieved (~30%), concurrent with intravenous cyanide infusion (0.167mg NaCN in 0.9% NaCl/min for 60 minutes). Animals were monitored with continuous gas exchange, hemodynamics, blood gases, cyanide levels, and diffuse optical spectroscopy, providing tissue oxy-and deoxyhemoglobin and cytochrome c oxidase measures in vivo. Intravenous cobinamide was administered in treatment arm animals and compared to control responses.RESULTS: Intravenous cobinamide reversed cyanide toxicity in these animals in the face of smoke induced carbon monoxide exposure, without evident adverse effects.CONCLUSIONS: Intravenous cobinamide shows promise as a potential antidote for cyanide poisoning in smoke inhalation victims, and an intramuscular formulation could potentially be administered in mass casualty exposure scenarios. Further validation and safety studies will be required for FDA approval of this promising agent.CLINICAL IMPLICATIONS: Treatment of fire smoke inhalation victims.DISCLOSURE: The following authors have nothing to disclose: Sasan Sani, Jangwoen Lee, Rene Patino, David Mukai, David Yoon, Sari Mahon, Gerry Boss, Steve Patterson, Matthew BrennerNo Product/Research Disclosure InformationBeckman Laser Institute, Irvine, CA. Language: en

Compounding parenteral methyltioninium chloride 1% solution in hospital pharmacy and risk assessment of preparation

BackgroundMethyltioninium chloride is an organic thiazine dye.It is used for management of methaemoglobinaemia, also as a visualising agent in surgical procedures, as an antidote for cyanide poisoning. It should be...

Radiolabeling and dose fixation study of oral alpha-ketoglutarate as a cyanide antidote in healthy human volunteers

Context. Radiolabeling and dose fixation study of alpha-ketoglutarate (A-KG). Objective. A-KG is a potential oral antidote for cyanide poisoning. Its protective efficacy in animals was best exhibited at a dose of 2.0 g/kg body weight, which when extrapolated to human is very high. The objective of this study was to reduce the dose of A-KG in humans with concomitant increase in its bioavailability, employing pharmacoscintigraphic techniques to assess kinetics in man. Materials and methods. A-KG was radiolabeled with technetium-99m pertechnetate (Tc-99m) and its purity, labeling efficiency, and stability in vitro were determined by instant thin layer chromatography. Time-dependent bio-absorption of the drug in rats and rabbits was assessed by gamma scintigraphy after oral administration of a tracer dose of 99mTc-A-KG mixed with nonradioactive A-KG at a concentration of 0.1–2.0 g/kg in the presence or absence of aqueous dilution. Furthermore, scintigraphy and radiometry studies were performed in healthy human volunteers using 5–20 g of A-KG, given in single or split doses followed by different quantity of water. Drug bioavailability was estimated periodically. Results. High radiolabeling (>97%) of A-KG with a stability of 24 h in vitro was obtained. Less than 1% absorption of the drug occurred within 20 min after A-KG was administered in animals at a concentration of 2.0 g/kg body weight. One-tenth reduction in dose increased the bioavailability to 15%. Significant improvement in gastric emptying of the drug was achieved when the drug was administered along with 1–5 mL of water. In humans, two doses of 10 g A-KG given at an interval of 10 min, followed by 300 mL of water, increased the drug bioavailability to 40% as compared to a single dose of 20 g. Discussion. Significant reduction in A-KG dose was achieved in humans as compared to the recommended dose in animals. Conclusion. Aqueous dilution improves the bioavailability of A-KG in humans.

Cyanide poisoning: pathophysiology and treatment recommendations.

This paper aims to assess and compare currently available antidotes for cyanide poisoning. Such evaluation, however, is difficult. Thus, extrapolation from the results of animal studies has potential pitfalls, as significant inter-species differences in response may exist, and these experiments often involve administration of toxin and antidote almost simultaneously, rather than incorporating a more realistic time delay before initiation of treatment. Direct inference from human case reports is also problematic; either because of uncertainties over the exposure levels involved (and hence the likely outcome without treatment), or because of difficulties in identifying the specific contribution of a particular antidote within the overall treatment regimen. Certainly an effort to compare the relative efficacy of cyanide antidotes produces equivocal findings, with no single regimen clearly standing out. Indeed, factors such as the risks of antidote toxicity to various individuals and other practical issues, may be more important considerations. There is therefore no single treatment regimen which is best for all situations. Besides individual risk factors for antidote toxicity, the nature of the exposure and hence its likely severity, the evolving clinical features and the number of persons involved and their proximity to hospital facilities, all need to be considered. Clinically mild poisoning may be treated by rest, oxygen and amyl nitrite. Intravenous antidotes are indicated for moderate poisoning. Where the diagnosis is uncertain, sodium thiosulphate may be the first choice. With severe poisoning, an additional agent is required. Given the various risks with methaemoglobin formers or with unselective use of kelocyanor, hydroxocobalamin may be preferred from a purely risk-benefit perspective. However the former alternatives will likely remain important.

Simultaneous determination of hydroxocobalamin and its cyanide complex cyanocobalamin in human plasma by high-performance liquid chromatography. Application to pharmacokinetic studies after high-dose hydroxocobalamin as an antidote for severe cyanide poisoning.

Hydroxocobalamin (OHCbl) is a powerful antidote for cyanide poisoning, via the formation of non-toxic cyanocobalamin (CNCbl). Plasmatic cobalamins were measured at 361 nm, after enrichment and purification on a short C18 precolumn (1% acetic acid; 1 ml min-1; 2 min), by back-flush elution on a C18 ODS-2 column [0.1 M sodium dihydrogenphosphate-methanol (63:27, v/v) (pH 4.0); 0.80 ml min-1]. The precision was 3.21 and 3.54% for 10 microM OHCbl and CNCbl, respectively. The method was used to study the pharmacokinetics of OHCbl and the formed CNCbl in severely poisoned patients.

Efficacy of ?-ketoglutaric acid as an effective antidote in cyanide poisoning in dogs

Efficacy of ?-ketoglutaric acid as an effective antidote in cyanide poisoning in dogs

Depletion of mitochondrial coenzyme A and glutathione by 4-dimethylaminophenol and formation of mixed thioethers

4-Dimethylaminophenol (DMAP), an antidote in cyanide poisoning, has been shown to produce kidney lesions in rats, to damage isolated rat kidney tubules and to impair mitochondrial functions as already described for 4-aminophenol. Since DMAP upon oxidation forms bis- and trissubstituted thioethers with GSH, it was anticipated that mitochondrial toxicity of DMAP might result from CoA depletion. In a model reaction DMAP was oxidized by oxyhemoglobin in the presence of CoA and GSH resulting in formation of tris-(CoA-S-yl)-DMAP, tris-(GSH-S-yl)-DMAP and two mixed thioethers, namely, (CoA-S-yl)-bis-(GSH-S-yl)-DMAP and (GSH-S-yl)-bis-(CoA-S-yl)-DMAP. The compounds were isolated by HPLC and identified spectroscopically, by amino acid analysis and Raney-Nickel desulfuration. Rat liver mitochondria (5 mg protein/ml) incubated under state IV conditions with 20 and 50 μM DMAP were depleted of GSH and total coenzyme A with formation of GSSG and the above-mentioned thioethers which were quantified by isotope dilution techniques using [ 14C]-labelled DMAP and the isolated, inactive thioethers. The results confirm earlier suggestions that part of the cytotoxicity of DMAP may result from depletion of vital mitochondrial thiols, particularly CoA. Since 4-aminophenol reacts analogously, similar cytotoxic effects can be expected from compounds which on (aut)oxidation form quinoid systems capable of 1.4-addition reactions with nucleophilic thiols.

Comparison of nitrite treatment and stroma-free methemoglobin solution as antidotes for cyanide poisoning in a rat model.

The standard nitrite/thiosulfate regimen for cyanide poisoning was tested in our rat model. By modifying the treatment regimen and the nitrite solution an effective antidote against an LD90 of cyanide could be produced. However, this treatment was effective against two times the LD90 only when administered ten minutes prior to cyanide injection. These results are in marked contrast to our results with stroma-free methemoglobin solutions (SFMS) which showed SFMS to be a highly effective antidote against four times the LD90 when administered 30 seconds after an intravenous injection of cyanide. SFMS proved to be an effective antidote for two times the LD90 when administered up to sixty seconds after the cessation of respiration.

Stroma-free methemoglobin solution as an antidote for cyanide poisoning: a preliminary study.

Effective treatment of cyanide poisoning requires rapid diagnosis, good supportive treatment and the use of a specific antidote. The currently available antidotes offer demonstrated efficacy along with significant potential adverse side effects. We have investigated an alternate approach to antidote therapy for cyanide poisoning by using Stroma-Free Methemoglobin Solution ( SFMS ). Rats injected with an LD100 intravenous dose of cyanide were treated with SFMS equal to 1.5% of their total body hemoglobin. There was a highly significant increase in the survival rate of the treated group compared to saline controls. The potential advantages of SFMS over current antidotes include an immediate onset of action, rapid elimination of cyanide from the body and a mode of action that doesn't compromise any of the patients' oxygen carrying capacity. SFMS shows promise as a significant adjunct in the treatment of cyanide poisoning.