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AIM: To describe the incidence of acute renal insufficiency after dipyrone overdose in children. METHODS: The medical records of all patients < or =18 years of age during a 3-year period presenting at Assaf Harofeh Medical Center due to toxic exposure were retrospectively reviewed. Patients suffering from dipyrone overdose were compared with all the other patients. RESULTS: 235 cases were included in the final analysis. Of these, 26 (11%) patients were exposed to dipyrone (median age 15 years). Three of the 26 patients (12%) had transient non-oliguric renal insufficiency. One other patient who did not receive dipyrone also developed transient renal insufficiency. CONCLUSIONS: Dipyrone overdose is frequent and may cause acute non-oliguric renal insufficiency. Renal function should be monitored in such patients.

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A fatal suicidal ingestion of drugs, together with activated charcoal, is reported. The death occurred 31 hours after the self-administration. The autopsy revealed a large amount of gastric content that appeared to be a compact mass of black color. Toxicologic analyses showed the presence of toxic levels of desalkylflurazepam and trazodone; metamizole and pridinol were also detected. The obtained results supported the hypothesis of a death due to acute intoxication delayed by the self-administration of activated charcoal, which elimination was probably hindered by the action of pridinol.

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INTRODUCTION: Dipyrone is an analgesic and antipyretic agent. The purpose of this study was to describe the pattern of dipyrone exposures reported to poison centers. METHODS: Human dipyrone exposures reported to 6 Texas poison centers from 1998 to 2004 were identified. Isolated and non-isolated cases were compared with respect to various factors. RESULTS: When compared to the Census, dipyrone exposures were significantly more likely to have been reported from regions closer to the Mexican border (53% vs 9%). Of 81 dipyrone exposures, 52 (64%) were isolated and 29 (36%) were non-isolated. Most of the dipyrone exposures occurred at the patient's own residence (72/76 or 95%) and the patients were more likely to be female (54/81 or 67%). Although the majority of both types of dipyrone exposures were adults (47/78 or 60%), children, less than 6 years of age, accounted for a higher proportion of isolated exposures (33% vs 10%) while a higher proportion of non-isolated exposures involved older children (28% vs 8%). Twenty-two percent (11/51) of isolated cases were intentional while 59% (17/29) of non-isolated cases were intentional. Of those cases with a known medical outcome, the medical outcome was no adverse clinical effect for 76% (16/21) of isolated exposures and 42% (8/19) of non-isolated exposures. The specific adverse clinical effects reported for isolated exposures were primarily neurological (n = 6), gastrointestinal (n = 4), and dermal (n = 3). The most frequently reported treatment for isolated exposures was some form of decontamination (n = 11). CONCLUSIONS: Isolated and non-isolated dipyrone exposures varied with respect to patient age, exposure reason, management site, medical outcome.

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BACKGROUND: Dipyrone is a pyrazolone derivative used as an analgesic and antipyretic. Agranulocytosis, dipyrone's most serious and potentially fatal adverse effect, has led to its withdrawal in several countries. However, agranulocytosis is subject to geographical variability, ratio with at risks ranging from 0.8-23.7. In many countries dipyrone is still widely used in adults and children and even as an over-the-counter (OTC) preparation. Information on the effects of dipyrone overdose is scanty. OBJECTIVE: To determine the demographic and clinical characteristics of dipyrone overdose. METHODS: Retrospective review of prospectively collected poison center data on acute exposure to dipyrone over a three-year period. The data were subjected to descriptive analysis. Mann-Whitney test and Chi-square analysis were performed where relevant. RESULTS: A total of 243 records met the inclusion and exclusion criteria. Median age was 17y (4m-83y), median amount 5 g (250 mg-45 g), and median time to consultation was 2 h (5 min-48 h). Toxic events (49) occurred in 39 (16%) patients; 57% of these were gastrointestinal and all were mild. Time to consultation was longer in the symptomatic patients (4 h vs. 1.5 h, respectively, p=0.001) and in children (8 h vs. 3.5 h in adults). Suicidal patients ingested significantly larger amounts (8 g vs. 3.7 g, respectively, p=0.001), as did patients with gastrointestinal symptomatology (7.5 g vs. 5 g in asymptomatics, p=0.001). No agranulocytosis was reported. DISCUSSION: Dipyrone overdose is associated with mild, mainly gastrointestinal toxicity; this was noted at a median dose of 7.5 g. Early gastrointestinal decontamination may have prevented toxicity. The suggested treatment includes gastrointestinal decontamination (if <1 h since ingestion) and supportive measures.

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A fatal suicidal intoxication with unusual drugs is reported. A 56-year-old man was found dead in his house; near by the corpse several empty drugs boxes were found. An autopsy was performed and the biological fluids were submitted to a full toxicological work-up. The analytical results supported the hypothesis of a death due to the acute baclofen (4-amino-3-(p-chlorophenyl)butyric acid) and dipyrone (sodium [N-(1,5-dimethyl-3-oxo-2-phenylpyrazolin-4-yl)-N-methylamino] methanesulfonate) intoxication.

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An 18-year-old girl swallowed 98 tablets of Novalgin (corresponding to 49 g metamizole) with suicidal intent. After stomach lavage she received forced diuresis for 14 hours. Metamizole metabolites in serum and urine were measured by thin-layer chromatography. After 24 hours the serum concentration of metamizole metabolites was still clearly elevated. Renal elimination amounted to 11 g metamizole. The patient survived the severe overdosage without significant organ abnormalities. This favourable course differs from reports of lethal intoxication with other pyrazolone derivatives, especially those with metamizole combination drugs. The forced diuresis proved to be a satisfactory elimination procedure. Biotransformation and elimination of the metamizole metabolites still continued after 24 hours.

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Pyrazolone intoxication accounts for most (52 percent) mild analgesic poisonings in West Germany. Severe and fatal intoxication with pyrazolones is, however, rare. In the German literature, only 50 cases have been described in the past 62 years; 80 to 90 percent of these were caused by aminopyrine, which was withdrawn from the West German market in 1978 and replaced by propyphenazone. Up to now, no fatal poisoning with propyphenazone has been reported. However, the signs and symptoms of severe intoxication are similar for both propyphenazone and aminopyrine. The acute toxicity of dipyrone is slightly lower than that of propyphenazone, whereas phenylbutazone and oxyphenbutazone clearly cause less severe reactions. Characteristic symptoms include impaired consciousness progressing to coma, and convulsions. In addition, arrhythmia and cardiogenic shock may occur. Severe aminopyrine intoxication may also be complicated by sudden apnea. Liver damage may develop after a latent period of about 24 hours, especially after phenylbutazone and oxyphenbutazone poisoning. Therapy involves supportive measures as well as gastric emptying by emesis or lavage, installation of medical charcoal, and induction of diarrhea or gut lavage. Although exact clinicotoxicologic data on hemoperfusion are not available as yet, distribution volumes, plasma half-lives, and endogenous plasma clearances as well as results of in vitro trials all suggest the efficacy of this procedure. Hemoperfusion with uncoated amberlite XAD-4 resin is, therefore, recommended for patients with severe pyrazolone intoxication.

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Thin-layer chromatographic (TLC) methods were developed for pharmacokinetic studies of major metamizole metabolites in serum and urine. These methods proved practicable, selective, accurate and sensitive with detection limits as follows: 4-methylaminoantipyrine 0.6 micrograms/ml serum and 2.0 micrograms/ml urine; 4-aminoantipyrine 0.16 micrograms/ml serum and 1.0 micrograms/ml urine; 4-acetylaminoantipyrine 0.14 micrograms/ml serum and 0.6 micrograms/ml urine; 4-formylaminoantipyrine 0.12 micrograms/ml serum and 1.0 micrograms/ml urine. Samples of 250 microliter suffice for TLC analysis. Following chromatographic separation, detection is performed in the ultraviolet range at 265 nm. Serum and urine levels were determined following a single oral dose of 1 g of metamizole sodium to eight volunteers. These results were compared with those following an accidental overdose of 49 g.

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