Severe toxicity is rare following deliberate self-poisoning with ibuprofen, and patients are usually either asymptomatic or develop only mild gastrointestinal toxicity. Although there have been nine other reported fatalities, co-existent factors have probably contributed to all of these deaths. We report here a fatality from isolated toxicity following self-poisoning with sustained-release ibuprofen. A year-old female presented after deliberate ingestion of up to g sustained-release ibuprofen, with a reduced level of consciousness, severe metabolic acidosis and haemodynamic compromise.
Despite intensive supportive management, gut decontamination with multidose activated charcoal and correction of the metabolic acidosis with sodium bicarbonate and haemofiltration, the patient did not survive.
Most patients with ibuprofen poisoning are either asymptomatic or have mild gastrointestinal symptoms; severe poisoning with ibuprofen is rare. We report the first death related to isolated sustained-release ibuprofen poisoning. Ibuprofen is a nonsteroidal anti-inflammatory drug NSAID commonly used as an analgesic, as an anti-inflammatory agent and as an anti-pyretic agent [ 1 , 2 ].
The predominant pharmacological action of ibuprofen is to inhibit the activity of cyclooxygenase, an enzyme crucial for the synthesis of prostaglandins. The subsequent inhibition of prostaglandin production leads to a reduction in inflammation, temperature and pain, both centrally and peripherally. Ibuprofen is manufactured and marketed as a 'normal' release preparation at a dose of mg three times a day or a sustained-release preparation at a dose of — mg once a day.
In the United Kingdom the 'normal'-release preparation is available on general sales licence, pharmacy and prescription, but the sustained-release preparation is available only as a 'prescription only medication'. There have been only nine previously reported fatalities following ibuprofen intoxication, although in eight of these cases other co-existent factors have probably contributed to death [ 3 - 11 ]. We report here the first case report of a fatality following isolated ingestion of sustained-release ibuprofen that did not respond to maximal supportive care with ante mortem and post mortem ibuprofen concentrations.
A year-old woman with no significant past medical history presented after ingestion of up to tablets of mg sustained-release ibuprofen, equivalent to approximately g. This estimate of the amount ingested was based on empty ibuprofen packets found near her. The patient was bought into the Emergency Department having been found collapsed and unconscious at home by her family, who had last seen her well approximately five hours previously. There was no history of vomiting, gastrointestinal haemorrhage or seizures prior to presentation at hospital.
On presentation she was haemodynamically compromised with a systolic blood pressure of 80 mmHg. The patient's initial electrocardiogram showed sinus rhythm, normal QRS duration and normal QT duration, but widespread myocardial ischaemia was noted. Paracetamol and salicylate concentrations were not detected on her admission blood samples. Arterial blood gases showed a severe metabolic acidosis with pH 6. The patient was commenced on epinephrine and norepinephrine for inotropic support in view of the significant hypotension, and the Guy's and St Thomas' Poisons Unit was contacted for further advice on management.
Since this was potentially a life-threatening ingestion of a sustained-release preparation of ibuprofen, it was recommended that multidose activated charcoal 50 g activated charcoal every 3—4 hours should be given via a nasogastric tube to try and reduce further absorption of ibuprofen from the gastrointestinal tract.
The patient's severe metabolic acidosis should be corrected with repeated doses of intravenous boluses of 8. It should be ensured that the patient is adequately filled with intravenous fluid to sustain blood pressure prior to the commencement of any additional inotropic support.
Despite fluid resuscitation and maximal infusion doses of epinephrine and norepinephrine, the patient remained hypotensive with a systolic blood pressure of 80 mmHg. Additionally her metabolic acidosis remained resistant to intravenous sodium bicarbonate and haemofiltration with a bicarbonate buffer, with only minor improvement to pH 7.
Samples of ante mortem serum were obtained following admission and were analysed for ibuprofen by the Medical Toxicology Laboratory in London. Post mortem samples of peripheral whole blood, urine, gastric contents and liver extract were analysed at the local toxicology laboratory for ibuprofen and other drugs. Ibuprofen concentrations were measured by high-pressure liquid chromatography with ultraviolet detection. No other drugs were detected in a broad toxicology screen; analysis of the ante mortem and post mortem serum samples only detected atracurium and lignocaine given following admission to the hospital.
The cause of death was probably directly related to the ibuprofen overdose, since there was no evidence of another cause of death at the post mortem examination. Of particular note there was no evidence of cerebral oedema, no underlying artherosclerotic disease of the coronary arteries and no evidence of previous myocardial infarction.
Although there was altered blood in the gastric fluid, there was no evidence of oesophageal or gastric erosions. Severe poisoning and death following poisoning with ibuprofen is extremely uncommon.
Most cases are either asymptomatic or experience mild gastrointestinal symptoms only [ 4 , 5 ]. In the case presented here the patient presented after ingestion of up to g sustained-release ibuprofen with a reduced Glasgow Coma Scale, a severe metabolic acidosis and significant haemodynamic compromise.
Despite meticulous supportive care initially in the Emergency Department and subsequently in the intensive care unit, attempted correction of her metabolic acidosis and the use of multidose activated charcoal to reduce further ibuprofen absorption from the gastrointestinal tract, the patient did not survive.
This is the first reported case of fatality following ingestion of sustained-release ibuprofen and the first fatality following isolated ibuprofen toxicity. Ibuprofen is a NSAID commonly used as an analgesic, as an anti-pyretic agent and as an anti-inflammatory agent [ 1 , 2 ].
Clinical features of toxicity of ibuprofen and other NSAIDs are predictable and occur due to an inhibition of cyclooxygenase activity. The American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists have published a position statement on the use of multidose activated charcoal [ 13 ]. In the case reported here a sustained-release preparation of ibuprofen was ingested, and therefore multidose activated charcoal was recommended to try and reduce further absorption of ibuprofen.
Another patient who was found dead who had recently been prescribed an mg preparation of ibuprofen, presumed to be a sustained-release preparation, had a post mortem total ibuprofen concentration of mg in the gastric contents [ 8 ]. Both our case and the other presumed sustained-release case would support the use of multidose activated charcoal in the management of patients who have ingested a sustained-release preparation of ibuprofen in any subsequent cases.
The toxicity of ibuprofen following self-poisoning has been reported in five large case series [ 3 - 5 , 10 , 14 ]. Histories in patients presenting with an overdose have been shown to be unreliable [ 16 ], however, so to try and predict those patients who are at risk of severe ibuprofen-induced toxicity, a nomogram based on the time since ingestion and the serum ibuprofen concentration, similar to that used for paracetamol acetaminophen , has been developed [ 4 ].
Nelson LS. Acute poisoning. Goldman-Cecil Medicine. Editorial team. Poisonous Ingredient Ibuprofen is sold over-the-counter and by prescription. Symptoms Symptoms may develop in the following areas: Eyes, ears, nose, throat, and mouth: Ringing in the ears Blurred vision Gastrointestinal: Diarrhea Heartburn Nausea, vomiting sometimes bloody Stomach pain possible bleeding in stomach and intestines Heart and blood: Low blood pressure shock and weakness Kidneys: Little to no urine production Lungs: Breathing -- difficult Breathing -- slow Wheezing Nervous system: Agitation , confusion , incoherent not understandable Drowsiness , even coma Convulsions Dizziness Headache severe Unsteadiness , trouble moving Skin: Rash Sweating Other:.
Before Calling Emergency The following information is helpful for emergency assistance: Person's age, weight, and condition Name of the product ingredients and strengths, if known Time it was swallowed Amount swallowed If the medicine was prescribed for the person However, DO NOT delay calling for help if this information is not immediately available.
Poison Control Your local poison control center can be reached directly by calling the national toll-free Poison Help hotline from anywhere in the United States. What to Expect at the Emergency Room The health care provider will measure and monitor the person's vital signs, including temperature, pulse, breathing rate, and blood pressure.
The person may receive: Activated charcoal Airway support, including oxygen, breathing tube through the mouth intubation , and breathing machine ventilator Blood and urine tests Chest x-ray Tube through the mouth into the stomach and small intestine to identify and treat internal bleeding endoscopy ECG electrocardiogram, or heart tracing Fluids through a vein intravenous or IV Laxative Medicines to treat symptoms.
Outlook Prognosis Recovery is likely with prompt medical treatment, except in very large overdoses. References Aronson JK. The medication is used by millions to treat:. The recommended dosage for adults is one or two milligram mg tablets every four to six hours. Adults should not exceed mg at once or 3, mg per day. Adults over the age of 60 should take as little ibuprofen as possible to manage their symptoms. Older adults have a higher risk of kidney and gastrointestinal side effects.
Ibuprofen for children is available in infant drops, liquids, and chewable tablets. Liquid measurements are given in milliliters mL. Make sure to read the label and measure carefully. Mixing ibuprofen with alcohol can also increase your risk of having serious side effects, like stomach or intestinal bleeding. Not everyone will experience symptoms of an ibuprofen overdose right away. Mild symptoms may include:. Infants who overdose may show signs of lethargy unresponsiveness or apnea temporary cessation of breathing following a more serious overdose of ibuprofen.
If you or someone you know has taken more than the maximum recommended dose of ibuprofen, contact your local poison center. You can call this number 24 hours a day. Stay on the line for further instructions. At the hospital, doctors will monitor breathing, heart rate, and other vital signs. A doctor may insert a tube through the mouth to look for internal bleeding.
Taking high doses of ibuprofen over long periods of time can also increase your risk of having a stroke or heart attack. Always read product labels carefully and take the smallest amount of ibuprofen possible that will help relieve your symptoms.
A safe dose for children is much less than that. If you or someone you know has taken more than this, call your local poison center or your local emergency services.
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