2,4-Dinitrophenol overdose - Everything old is new again.

A complete case example of a fatal 2,4-dinitrophenol (DNP) overdose involving a 23-year-old male is described. Included are details of not only the patient's presentation symptoms and treatment, but also the subsequent findings of the coronial investigation process including the autopsy, post-mortem computed tomography (PMCT) scanning and toxicological analysis and results. The patient presented with elevated temperature, heart rate and blood pressure. Multiple treatments were conducted to counteract these symptoms, however the patient died approximately 1.5 hours after hospital admission and some 4.5 hours after the DNP was initially consumed. Autopsy revealed the presence of cardiovascular disease that was contributory to death and post-mortem computed tomography showed evidence of decompositional intravascular gas in the neck, head, face, lower abdomen, heart and hepatic systems. Toxicological analysis was completed by protein precipitation with methanol and subsequent instrumental analysis by LC/MS/MS in negative ion mode. The antemortem blood specimen showed the presence of tadalafil, two anabolic steroids and a DNP concentration of 110 mg/kg which is consistent with other reported DNP fatalities. Despite the small amount of time between the antemortem specimen collection and death, the DNP concentration identified in the femoral blood post-mortem specimen was comparably low (5.5 mg/kg). DNP concentrations also reduced during an extended period of specimen storage prior to analysis indicating some instability in biological specimens even when refrigerated or frozen. DNP was found to be distributed primarily in the aqueous tissues (blood, vitreous, bile) rather than solid matrices (liver, kidney, muscle).

Toxicoepidemiology and predictors of death in 2,4-dinitrophenol (DNP) toxicity.

INTRODUCTION: 2,4-Dinitrophenol (DNP) is a highly toxic industrial chemical that is sometimes misused to reduce body fat. Toxicity following ingestion of DNP has recently become more common in the United Kingdom. This research was performed to document the frequency of DNP toxicity as reported to poisons centres in the United States (US) and United Kingdom (UK) and to identify the clinical features associated with fatality. METHODS: Calls to UK and US poisons centres involving systemic exposure to DNP were extracted for the 12 calendar years 2007-2018. These were analysed using univariate and multivariate statistical techniques. RESULTS: There were 204 cases (n = 86, US; n = 118, UK) of systemic DNP exposure identified, of which 86% were under the age of 40 and 71% were males. Over the study period the incidence of reported DNP toxicity was higher in the United Kingdom than the United States (1.78 vs. 0.26 cases per million population) and annual case numbers have increased in both countries since 2011. Case fatality was high and did not differ significantly between countries (US 11.6%; 95% CI: 6.4-20.1%: UK 16.9%; 95% CI: 11.3-24.7%; X2(1) = 1.12, p = 0.29). Univariate analysis demonstrated significant associations between risk of death and the presence of hypoglycaemia (OR = 17.1, 95% CI 1.7-174.3), hypertonia (OR = 12.9, 95% CI 3.5-47.6), acidosis (OR = 12.5, 95% CI 4.8-32.9), raised lactate (OR = 8.3, 95% CI 2.4-28.4), hyperpyrexia (OR = 6.5, 95% CI 2.8-15.2), tachycardia (OR = 6.4, 95% CI 2.5-16.4), agitation or confusion (OR = 6.0, 95% CI 2.6-13.7), hypertension (OR = 5.6, 95% CI 1.9-16.4) and tachypnoea/dyspnoea (OR = 2.8, 95% CI 1.2-6.1). After backwards stepwise logistic regression, the following were retained as significant independent predictors of mortality: acidosis (OR = 5.4, 95% CI: 1.8 - 16.5), tachycardia (OR = 3.6, 95% CI: 1.2 - 11.0), agitation/confusion (OR = 3.4, 95% CI: 1.2 - 9.7) and hyperpyrexia (OR = 2.8, 95% CI: 1.0 - 7.4). DISCUSSION: DNP toxicity is uncommonly reported to poisons centres but has recently become more frequent in the United States and United Kingdom. Tachycardia, hyperpyrexia, acidosis, and agitation/confusion are independent risk factors for mortality and their presence should prompt rapid escalation to an intensive care environment for aggressive supportive treatment and monitoring.

Death of an apprentice bodybuilder following 2,4-dinitrophenol and clenbuterol intake.

We present the case of a 17-year-old man, who died after 2,4-dinitrophenol (DNP) and clenbuterol consumption, which he likely took for physical enhancement. Forensic post-mortem examination revealed a yellowish skin colour and nonspecific signs of asphyxia. Analytical confirmation of the intoxication was obtained in blood and urine, with high levels of DNP and clenbuterol. Both of these substances are used by bodybuilders as DNP enhance lipolysis and clenbuterol has anabolic properties, but their toxicity is underestimated. DNP uncouples oxidative phosphorylation, leading to thermogenesis and even relatively small doses can cause fatal hyperthermia. Clenbuterol is a ß2 agonist that causes electrolyte disturbances (hypokalemia and hyperglycemia mostly) and death have been described through coronary vasospasm. Given the circumstances in which the body was found and toxicological results, we believe the cause of death to be fatal hyperthermia from DNP intake. These substances are illegal in many countries, but easily bought online. Through this availability, the last decades have seen an increase of fatal intoxications. Websites selling them are regularly closed by French public authorities and Interpol, but unfortunately it seems insufficient.

Role of dantrolene in dinitrophenol (DNP) overdose: A continuing question?

BACKGROUND: 2,4-Dinitrophenol (DNP) is a known uncoupler of oxidative phosphorylation that clinically results in hyperthermia, tachycardia, tachypnea, and metabolic acidosis. Overdoses of DNP are often fatal and there is no specific reversal therapy. Dantrolene interferes with calcium release in skeletal muscle and is traditionally used to treat malignant hyperthermia. There has been limited published data on its use in DNP toxicity. We present two cases of DNP toxicity that were treated with dantrolene. CASE 1: A 22-year-old male presented following an overdose of his bodybuilding supplements including DNP. He became altered, tachycardic, and hyperthermic to 40.0C. He required intubation and aggressive cooling. He received multiple doses of dantrolene over the initial 36 h with resolution of his hyperthermia. He was extubated and discharged home on hospital day 6. CASE 2: A 20-year-old male presented following a staggered ingestion of DNP. He was tachypneic and tachycardic on arrival. He became hyperthermic to 40.2C and required intubation. He underwent aggressive cooling and received 200 mg of IV dantrolene. His temperature normalized, however, he expired 4 h after ED arrival. CONCLUSION: DNP toxicity has limited treatment options. Dantrolene may ameliorate the hypermetabolic state in DNP toxicity by lessening excitation-contraction coupling in muscle cells and improving the associated hyperthermia. Our cases demonstrate the hyperthermia reducing effects of dantrolene in DNP toxicity and contribute to the existing literature on this topic. Being aware of the possible use of dantrolene to treat the associated hyperthermia could assist emergency physicians in the treatment of DNP toxicity.

Dantrolene is not the answer to 2,4-dinitrophenol poisoning: more heated debate.

There has been a resurgence in the use of 2,4-dinitrophenol, C6H4N2O5 (DNP) recently as an illegal weight loss drug. We present a case of a healthy 25-year-old girl who took two tablets of DNP, purchased from an overseas online retailer. She was managed with aggressive, invasive cooling measures and 2.5 mg kg-1 dantrolene. Despite this, her temperature continued to rise exponentially to 41.5°C. Cardiac arrest occurred and resuscitation was unsuccessful. To our knowledge, this is the first reported case of the ineffective use of dantrolene in acute DNP poisoning. We review the pathophysiology of DNP toxicity and argue that the use of dantrolene therapy is biochemically implausible, based on poor evidence and likely to be futile. We have contacted the UK National Poisons Information Service (NPIS/TOXBASE) to propose changes to the management of acute DNP toxicity.

Dinitrophenol (DNP) Fatality Associated with a Falsely Elevated Salicylate Level: a Case Report with Verification of Laboratory Cross Reactivity.

INTRODUCTION: 2,4-Dinitrophenol (DNP) is a known uncoupler of oxidative phosphorylation that clinically leads to hyperthermia, tachycardia, tachypnea, and metabolic acidosis. Intentional overdoses of DNP are often fatal. We present an analytically confirmed fatal case of DNP overdose with a falsely positive elevated salicylate concentration. We further explored this cross reactivity of DNP with two salicylate assays. METHODS: Clinically relevant serial dilutions of DNP were prepared in drug-free serum and analyzed using two different colorimetric NADH/NAD-based analytical methodologies. RESULTS: The enzymatic salicylate assay demonstrated a reproducible false elevation of salicylate starting at a DNP level of 100 mg/L while the EMIT-based methodology was without any such interference at the maximum concentration tested (150 mg/L). CONCLUSIONS: DNP cross reacts with some salicylate assays. This knowledge is important for providers, as there are significant variations in the management of DNP versus salicylate toxicity.

Death within 44 days of 2,4-dinitrophenol intake.

We report the case of a 50-year-old obese man (115 kg body mass at 1.77 m height), who started taking 2,4-dinitrophenol (DNP) for weight reduction 44 days before his death. After 43 days of taking DNP, the man showed signs of intoxication with nausea, vomiting, and attacks of sweating. After admission to a hospital where the man concealed his DNP intake, sinus tachycardia, tachypnea, and general unrest were noted. The patient died 9 h after the onset of those symptoms. Upon autopsy, a yellowing of palms and soles was striking. The initially uncertain cause of death could only be clarified by the forensic toxicological examinations and subsequent police investigations. Finally, the man had a total intake of 12.3 g of DNP in 44 days which is relatively high compared to other lethal DNP intoxications.

Beware the yellow slimming pill: fatal 2,4-dinitrophenol overdose.

An industrial chemical, 2,4-dinitrophenol (DNP), has found use as a weight loss drug. It is extremely toxic in overdose and has a narrow therapeutic window with significant interindividual variability in metabolism. The rise in internet-based sales and distribution of this drug has seen an increased incidence of both accidental and intentional overdose presenting to emergency departments across the UK. No antidote currently exists and overdose is often fatal despite management based on current recommendations. We report a case of intentional overdose of DNP in a young man and discuss the current treatment guidelines. The case highlights the need for an increased awareness among frontline medical staff of the effects of DNP poisoning and questions the need for a more aggressive approach in the management of acute toxicity.

Early Changes of Peripheral Blood Lymphocyte Subpopulations in Patients with Occupational 2,4-dinitrophenol Poisoning.

2,4-dinitrophenol (DNP), an organic compound which frequently used in industry, is considered to have high toxicity. This study aimed to investigate the early changes of lymphocyte subpopulations in patients with occupational 2,4-DNP poisoning. Totally 9 patients with acute occupational 2,4-DNP poisoning and 30 healthy volunteers as control were enrolled. The patients received immediately comprehensive supportive treatments, including large-dose glucocorticoid and repeated hemoperfusion (HP). The ratio of CD4+/CD8+ T cells were significantly higher in patients upon admission compared to healthy controls (P < 0.01); however, counts of total lymphocytes, CD3+, CD3+CD4+, CD3+CD8+, B (CD19+), and natural killer (NK) cells (CD16+CD56+) were significantly reduced (all P < 0.001). The NK cell count was negatively correlated with initial plasma 2,4-DNP concentration (r = -0.750, P = 0.026). Thus, acute occupational 2,4-DNP poisoning was accompanied by immediate complex immune cell reactions, especially NK cells might play important role in severe 2,4-DNP poisoning.

[Fatal course following poisoning with an illegal weight-reducing agent]. / Fatalt forløb efter forgiftning med illegalt slankemiddell.

DNP is a weight-reducing agent, which has been revived through sale over the Internet. DNP uncouples the oxidative phosphorylation in cells, leading to an excessive production of heat. A 39-year-old male ingested four grams of DNP and developed severe muscular stiffness and eventually cardiac arrest. Intubation was unsuccessful, and tracheotomy was performed on scene. Ventilation proved impossible, and the patient was declared dead in the pre-hospital setting. Doctors need to recognize potential lethal intoxications. Symptomatic treatment is warranted.

Evaluation of efficacy of resin hemoperfusion in patients with acute 2,4-dinitrophenol poisoning by dynamic monitoring of plasma toxin concentration.

OBJECTIVE: The intoxications caused by 2,4-dinitrophenol (2,4-DNP), even death, have been frequently reported in recent years. This study aims to investigate the dynamic changes of plasma toxin concentration and explore the clinical value of resin hemoperfusion (HP) in the treatment of patients with acute 2,4-DNP poisoning. METHODS: We reported 16 cases of acute 2,4-DNP poisoning through occupational exposure due to ignoring the risk of poisoning. The blood samples were collected from the 14 survivors. According to the different treatments of resin HP, the survivors were divided into routine HP (n=5) and intensive HP (n=9) groups. Ultra high performance liquid chromatography/ tandem mass spectroscopy (UPLC-MS/MS) was used to detect the 2,4-DNP concentration in plasma in this study. RESULTS: The 14 survivors recovered very well after treatment. The initial plasma 2,4-DNP concentrations (C1) of survivors ranged from 0.25 to 41.88 µg/ml (mean (12.56±13.93) µg/ml). A positive correlation existed between initial plasma 2,4-DNP concentration (C1) and temperature. The elimination of 2,4-DNP was slow and persistent, and the total clearance rates of plasma toxin from the 1st to 3rd day (R3), the 3rd to 7th day (R3-7), and the 1st to 7th day (R7), were only (53.03±14.04)%, (55.25±10.50)%, and (78.29±10.22)%, respectively. The plasma toxin was cleared up to 25 d after poisoning in most of the patients. The R3, R3-7, and R7 in the intensive HP group were all apparently higher than those in the routine HP group, with statistical significance (P<0.05). Simultaneously, the elimination half-life (t1/2) of 2,4-DNP in the intensive HP group was apparently shorter than that in the routine HP group, with statistical significance (P<0.05). CONCLUSIONS: The clinicians should be aware of this slow and persistent process in the elimination of plasma 2,4-DNP. Higher initial plasma toxin concentration resulted in a more severe fever for the patient. According to the limited data, longer and more frequent resin HP may accelerate to eliminate the poison.

Increasing frequency of severe clinical toxicity after use of 2,4-dinitrophenol in the UK: a report from the National Poisons Information Service.

OBJECTIVE: 2,4-Dinitrophenol (DNP) increases energy consumption by uncoupling oxidative phosphorylation. Although not licensed as a medicine, it is sometimes used by 'body sculptors' and for weight loss as a 'fat burning' agent. This research was performed to characterise patterns of presentation, clinical features and outcomes of patients reported to the National Poisons Information Service (NPIS) in the UK after exposure to DNP. METHODS: NPIS telephone enquiry records and user sessions for TOXBASE, the NPIS online information database, related to DNP, were reviewed from 1 January 2007 to 31 December 2013. RESULTS: Of the 30 separate systemic exposures to DNP reported by telephone to NPIS during the study period (27 males, 3 females, with a median age of 23.5 years), there were 3 during 2007-2011 (inclusive), 5 during 2012 and 22 during 2013. TOXBASE user sessions also increased sharply from 6 in 2011 to 35 in 2012 and 331 in 2013. The modes of exposure reported in telephone enquiries were chronic (n=2), acute (n=12) and subacute (n=16). Commonly reported clinical features were fever (47%), tachycardia (43%), sweating (37%), nausea or vomiting (27%), skin discolouration or rash (23%), breathing difficulties (23%), abdominal pain (23%), agitation (13%) and headache (13%). There were five (17%, 95% CI 6.9% to 34%) fatalities, four involving acute overdose. CONCLUSIONS: The study indicates a substantial recent increase in clinical presentations with toxicity caused by exposure to DNP in the UK with an associated high mortality. Further steps are needed to warn potential users of the severe and sometimes fatal toxicity that may occur after exposure to this compound.

[Effects of hemoperfusion on the patients with acute toxication of 2, 4-dinitrophenol].

OBJECTIVE: To explore the management strategies of acute toxication of 2, 4-dinitrophenol by hemoperfusion. METHODS: A total of 14 patients with acute toxication of 2, 4-dinitrophenol were admitted on September 14, 2009. And they were divided into severe and mild groups according to the severity of clinical manifestation. All patients in both groups received 2-hour blood perfusion within 2 hour post-admission. Their clinical manifestations, laboratory parameters and 2, 4-dinitrophenol levels were carefully observed before and after each perfusion. And oxygenation, intravenous use of furosemide, corticosteroids and symptomatic therapies were simultaneously given to improve general conditions. RESULTS: In serious group, the levels of before and after the first perfusion were 28.21(15.56-45.23) and 16.11(10.10-27.52) mg/L (P < 0.05), respectively. In both groups, all levels of 2, 4-dinitrophenol were significantly reduced before and after each perfusion (all P < 0.05). The patients in severe group would get relieved after 3 vs 2 perfusions in mild group. In severe group, there was a remarked decrease in neutrophil and platelet count after perfusion than those in mild group. The liver enzymes and blood lipids in both groups after therapy significantly elevated than those before therapy (all P < 0.05). CONCLUSION: Crucial for managing acute toxication of 2, 4-dinitrophenol, early hemoperfusion reduces mortality.

2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death.

2,4-Dinitrophenol (DNP) is reported to cause rapid loss of weight, but unfortunately is associated with an unacceptably high rate of significant adverse effects. DNP is sold mostly over the internet under a number of different names as a weight loss/slimming aid. It causes uncoupling of oxidative phosphorylation; the classic symptom complex associated with toxicity of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea, eventually leading to death. Fatalities related to exposure to DNP have been reported since the turn of the twentieth century. To date, there have been 62 published deaths in the medical literature attributed to DNP. In this review, we will describe the pattern and pathophysiology of DNP toxicity and summarise the previous fatalities associated with exposure to DNP.

Clinical features and treatment in patients with acute 2,4-dinitrophenol poisoning.

OBJECTIVE: To report clinical features and treatment of 16 cases of acute 2,4-dinitrophenol poisoning. METHODS: A total of 16 patients suffering from acute poisoning due to non-oral exposure to 2,4-dinitrophenol were sent to our hospital. Two died within 3 h after admission, while the other 14 responded to supportive treatment and hemoperfusion. Clinical features and treatment of the patients were retrospectively analyzed and presented. RESULTS: Fourteen patients recovered and were discharged after four to six weeks of treatment. No obvious poisoning sequelae were found in the three-month follow-up. CONCLUSIONS: Non-oral exposure to 2,4-dinitrophenol is toxic. Hemoperfusion and glucocorticoid treatments may be efficient measures to prevent mortality, but this requires further study.

2, 4-dinitrophenol poisoning caused by non-oral exposure.

2, 4-Dinitrophenol (2, 4-DNP) is widely used in industry, but recently, poisoning through consumption for weight control has been frequently reported. We report the cases of two patients whose deaths were attributed to occupational and non-oral exposure of 2, 4-DNP. They were all poisoned through skin absorption and respiratory tract inhalation; common features were excessive sweating, hyperthermia, tachycardia, clouded consciousness and asystole. Because of the lack of specific early symptoms, effective antidotes and the means of washing the contamination from the skin, their arrival in hospital was delayed and the supportive therapy was ineffectual. Cardiac arrest occurred quickly and unexpected after admission.