Anaphylactic reaction after intravenous dipyrone

doi:10.1016/j.acpain.2007.08.025

Acute Pain

Volume 9, Issue 4, December 2007, Pages 221-227

https://doi.org/10.1016/j.acpain.2007.08.025 Get rights and content

Summary

Dipyrone (metamizol), a non-opioid analgesic, is widely used for acute and chronic pain management. Although not marketed in all countries because of concerns of possible side effects like agranulocytosis, this potent analgesic is frequently used worldwide.

A severe anaphylactic reaction without any cutaneous symptoms was observed after intravenous infusion of dipyrone 1 g. Further symptoms were a short lasting increase in airway pressure and a pronounced generalized oedema. Circulatory arrest required cardiopulmonary resuscitation. Pre-existing β-blockade aggravated poor response to adrenaline. Recovery of the patient was uneventful.

Previous case reports demonstrated that symptoms of allergic reaction after dipyrone might vary considerably. Erythema, bronchospasm and eyelid-/angio-oedema might present alone or in combination. Sole cardiovascular collapse produced by extreme generalized oedema and consecutive hypotension occurred after i.v. administration during anaesthesia. Risk factors for severe dipyrone induced allergy are: allergies/intolerability of dipyrone and other non-opioids and bronchial asthma. However, allergic reaction after previous intake of dipyrone without side effects has been described.

Introduction

The pyrazolone derivate dipyrone (metamizol) belongs to the non-opioid analgesics and is used for acute and chronic pain management [1]. This drug can be administered orally as tablets or drops, intravenously, intramuscularly or rectally in children and adults and provides analgesic, antipyretic and spasmolytic properties. Therefore, it covers a broad spectrum of indications. In Germany, dipyrone is a widely prescribed drug for acute and chronic pain management. In the postoperative setting, it is one of the most powerful non-opioid analgesics marketed up to date. Its opioid sparing effect has been demonstrated in several investigations [2], [3]. Since it lacks side effects on the gastrointestinal tract and has no clinically significant influence on the coagulation pathway, it is well tolerated by patients.

However, dipyrone is banned in some countries because of its association with incidents of agranulocytosis [4]. The frequency of this adverse effect is still controversial [5], [6], [7], [8]. Nevertheless, dipyrone has remained very popular (e.g. in Austria, Belgium, France, Germany, Italy, the Netherlands, Turkey, Spain, Switzerland, South Africa, Latin America, Russia) since it is efficacious at low cost and can be administered by different routes. However, like in other non-opioid analgesics, allergic and anaphylactic reactions may occur. A case report with detailed documentation of the anaphylactic event and a review of cases presenting a comparable adverse drug reaction are reported.

Section snippets

Case report

A 75-year-old woman (67 kg, 168 cm) was scheduled for gynaecologic laparotomy because of a cystic adnex tumor. A history of endocarditis in 1983, a liver cirrhosis Child A of unknown origin, and a partial thrombosis of the portal vein was reported. Regular medication consisted of propanolol 2× 10 mg, furosemide 50 mg and jodid 200 μg/day. The patient suffered from an insulin dependent type II diabetes mellitus and during preoperative evaluation she mentioned an allergic reaction with urticaria

Discussion

In a Swiss investigation the rate of severe life-threatening anaphylaxis with circulatory signs was found to be 7.9–9.6/100,000 inhabitants per year [9]. Focussing on hospital admissions only, anaphylactic and anaphylactoid reactions are estimated to occur at a rate of 1:5000 [10]. For most non-opioid analgesics, the incidence of anaphylaxis was in the range of 5–15 cases/100,000 exposed patients [11]. Among the individual analgesics, the estimates ranged from 2.1/100,000 for oral aspirin to

Conclusions

•
Symptoms of allergic reaction after dipyrone might vary considerably. Erythema, bronchospasm and eyelid-/angio-oedema might present alone or in combination.
•
Sole cardiovascular collapse produced by extreme generalized oedema and consecutive hypotension is described after i.v. administration during anaesthesia.
•
Risk factors for severe dipyrone induced allergy are: allergies/intolerability of dipyrone and other non-opioids (patient's history, allergy pass!) and bronchial asthma
•
Allergic reaction to

Conflict of interest statement

There is no conflict of interest.

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Cited by (11)

Dipyrone as pre-emptive measure in postoperative analgesia after tonsillectomy in children: a systematic review
2021, Brazilian Journal of Otorhinolaryngology
Citation Excerpt :
In all clinical trials of dipyrone use in the postoperative period of children, the incidence of nausea and vomiting was the same between the active group and the placebo. There are several case reports describing anaphylaxis after administration of the drug.51 For most non-opioid analgesics, the incidence of anaphylaxis is in the range of 5–15 cases/100,000 exposed patients.52
Tonsillectomy is the 2nd most common outpatient surgery performed on children in the United States of America. Its main complication is pain, which varies in intensity from moderate to severe. Dipyrone is one of the most widely used painkillers in the postoperative period in children. Its use, however, is controversial in the literature, to the point that it is banned in many countries due to its potential severe adverse effects. Because of this controversy, reviewing the analgesic use of dipyrone in the postoperative period of tonsillectomy in children is essential.
The aim of this study was to review the analgesic use of dipyrone in the postoperative period of tonsillectomy in children.
Systematic review of the literature, involving an evaluation of the quality of articles in the databases MEDLINE/Pubmed, EMBASE and Virtual Health Library, selected with a preestablished search strategy. Only studies with a randomised clinical trial design evaluating the use of dipyrone in the postoperative period of tonsillectomy in children were included.
Only 2 randomised clinical trials were found. Both compared dipyrone, paracetamol, and placebo. We were unable to carry out a metanalysis because the studies were too heterogenous (dipyrone was used as pre-emptive analgesic in one and only postoperatively in another). The analgesic effect of dipyrone, measured by validated pain scales in childhood, was shown to be superior to placebo and similar to paracetamol. It appears that dipyrone exhibits a profile suitable for use in children. However, the scarcity of randomised clinical trials evaluating its analgesic effect in this age group leads to the conclusion that more well-designed studies are still needed to establish the role of dipyrone in the postoperative period of tonsillectomy in children.
Severe anaphylaxis reaction by dipyrone without a history of hypersensitivity. Case report
2017, Revista Colombiana de Anestesiologia
La seguridad de la dipirona ha sido objeto de numerosos debates, ya que pueden aparecer reacciones alérgicas graves cuya incidencia estimada es de 1 en 5.000 administraciones parenterales.
Se reporta un caso de una paciente que luego de una infusión con dipirona presenta tos, prurito faríngeo, disnea, cianosis generalizada y deterioro del estado de consciencia. Se hizo el diagnóstico de shock anafiláctico sin antecedentes previos de hipersensibilidad al medicamento que, a pesar del tratamiento con intubación orotraqueal, adrenalina, hidrocortisona, cloruro de sodio y bicarbonato de sodio, resultó fatal.
Pueden presentarse casos de grave hipersensibilidad en pacientes sin antecedentes de esta, lo que hace importante reconocer este riesgo en nuestros pacientes.
The safety of dipyrone has been the subject of several debates; severe allergic reaction can occur; its incidence is 1 in 5.000 parenteral administrations.
A case of a patient who following an infusion with dipyrone has a cough, pharyngeal pruritus, dyspnea, cyanosis and generalized impairment of consciousness. The diagnosis of anaphylactic shock by dipyrone in a patient without hypersensitivity precedent is reported, despite treatment with endotracheal intubation, adrenaline, hydrocortisone, sodium chloride and sodium bicarbonate, which proved fatal.
Serious cases of hypersensitivity may occur in patients with no history of it; it is important recognized this risk in our patients.
Pain management assessment in children with limb fractures in an emergency service
2016, Revista Colombiana de Anestesiologia
El parámetro de medición de la intensidad del dolor en niños más usado es la escala revisada de caras de dolor (FPS-R). El manejo del dolor depende del nivel de atención y al conocimiento que el médico tenga respecto a la dosificación, indicación y efectos secundarios de los medicamentos disponibles.
Evaluar el manejo de dolor en pacientes entre 3 y 17 años con fracturas de extremidades mediante escala (FPS-R) en las primeras 6 h.
Es una cohorte observacional, en pacientes entre 3 y 17 años con fracturas en extremidades, entre octubre de 2013 y enero de 2014. Se excluyeron pacientes con comorbilidades que impliquen presencia de dolor crónico. La escala se aplicó en cuatro ocasiones según las instrucciones validadas, al ingreso, a la hora, a las tres h y a las seis h.
Se evaluaron 60 pacientes, identificando 4 esquemas farmacológicos: monoterapia con dipirona (63,3%), terapia conjugada de dipirona más tramadol (10%), monoterapia con tramadol (8,3%), monoterapia con acetaminofén (6,6%).
La dipirona logró en promedio disminuir 1,7 puntos en la FPS-R durante la primera hora, para el final del seguimiento a las 6 h disminuyó en promedio 4 puntos en la escala; el tramadol logró disminuir 1,6 puntos y 4,6 puntos respectivamente. La asociación dipirona+tramadol no logró disminución significativa de dolor en la primera hora.
La inmovilización de la fractura es el pilar de la analgesia pero no suficiente para el manejo del dolor. La monoterapia con dipirona o tramadol tuvieron los mejores resultados en cuanto a disminución de la intensidad de dolor, la combinación dipirona–tramadol no es mejor que la monoterapia.
The tool most widely used for measuring the intensity of pain in children is the faces pain score - revised (FPS-R). Pain management depends on the level of care and the knowledge of the physician regarding dosing, indications and side effects of the medications available for use.
To assess pain management in patients 3 to 17 years of age with limb fractures using the FPS-R within the first 6 hours.
Observational cohort of patients 3-17 years of age presenting with limb fractures between october 2013 and january 2014. Patients with comorbidities associated with chronic pain were excluded. The tool was administered four times in accordance with the validated instructions – on admission, at first hour, at three hours and at six hours.
Overall, 60 patients were assessed and 4 pharmacological regimens were identified: dipyrone alone (63.3%), combined therapy with dipyrone plus tramadol (10%), tramadol alone (8.3%), acetaminophen alone (6.6%).
The mean pain intensity reduction with the use of dipyrone was 1.7 points on the FPS-R within the first hour, with a mean reduction of 4 points by the end of the six hours of follow-up. With tramadol, pain reduction was 1.6 points and 4.6 points, respectively. The combined use of dipyrone plus tramadol did not result in significant pain reduction within the first hour.
Fracture immobilization is the mainstay for analgesia but it does not suffice as a form of pain management. Monotherapy with dipyrone or tramadol resulted in the best pain reduction, whereas the combined use of dipyrone plus tramadol was not better than the use of either medication alone.
Recommendations for the perioperative use of dipyrone: Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association
2019, Anaesthesist
Recommendations for the perioperative use of dipyrone: Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association
2019, Chirurg
Recommendations for the perioperative use of dipyrone: Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association
2019, Schmerz

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Anaphylactic reaction after intravenous dipyrone

Summary

Introduction

Section snippets

Case report

Discussion

Conclusions

Conflict of interest statement

Lancet

Br J Anaesth

Ann Fr Anesth Reanim

Single-dose dipyrone for acute postoperative pain

Cochrane Database Syst Rev

The opiate sparing effect of dipyrone in postoperative pain therapy with morphine using a patient-controlled analgesia system

Intens Care Med

Postoperative analgesie nach endoskopischen abdominellen Eingriffen Eine randomisierte Doppelblindstudie zur perioperativen Wirksamkeit von Metamizol

Chirurg

Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole)

Eur J Clin Pharmacol

The incidence of metamizole sodium-induced agranulocytosis in Poland

J Int Med Res

A prospective study of the incidence of agranulocytosis and aplastic anemia associated with the oral use of metamizole sodium in Poland

Med Sci Monit

Agranulocytosis associated with dipyrone (metamizol)