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Journal of General and Emergency Medicine

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Case Report

A Difficult-to-diagnose Case of Caffeine Intoxication

Ryo Asada, Hiromichi Naito, Kohei Tsukahara, Hiromi Ihoriya, Ryo Tanabe, Yasuhiro Koide, Yoshinori Kosaki, Atsunori Nakao

Correspondence Address :

Atsunori Nakao, MD
Department of Emergency
Critical Care, and Disaster Medicine
Okayama University Graduate School of Medicine
Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558
Japan
Tel: +81-86-235-7426, Fax: +81-86-235-7427
Email: qq-nakao@okayama-u.ac.jp

Received on: May 06, 2018, Accepted on: May 17, 2018, Published on: May 25, 2018

Citation: Ryo Asada, Hiromichi Naito, Kohei Tsukahara, et al. (2018). A Difficult-to-diagnose Case of Caffeine Intoxication

Copyright: 2018 Atsunori Nakao, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Abstract
Caffeine causes the release of noradrenaline and sensitizes the dopamine receptors. Although intentional or unintentional caffeine abuse is relatively common, making an accurate caffeine intoxication diagnosis can be difficult. The present case emphasizes the usefulness of computed tomography (CT) in diagnosing a drug overdose by detecting high-density deposits in the alimentary tract, suggesting the presence of recently ingested
overdoses of drugs. In addition to typical clinical symptoms, CT findings helped us determine caffeine intoxication instead of searching for all potentially relevant information. A 19-year-old liver-transplant recipient was transferred to our emergency center with a disturbed mental state, seizure, and vomiting. The patient developed symptoms including tachycardia, tachypnea, myoclonus, muscular rigidity, and a large amount of sweating.
Routine blood test findings were unremarkable, with normal blood sugar levels and negative routine drug urine screening. Although brain CT and magnetic resonance imaging demonstrated no abnormalities in the intracranial region, abdominal CT detected multiple high-density deposits in the gastrointestinal tract. Based on the radiological and clinical findings, an overdose of undetermined drugs was suspected. The patient was treated with intratracheal intubation, respiratory support, and fluid resuscitation and recovered from coma within 24 hours. The patient's family member had found an empty bottle of caffeine pills the following day, and the patient reported that he had attempted suicide by ingesting 78 tablets containing 250 mg of caffeine each (total 16.5 grams). Blood caffeine concentration measured at the first visit was more than 50 mg/L (above the measurement limitation). Serious caffeine intoxication is uncommon, but can be fatal, mainly due to ventricular and supraventricular dysrhythmias. Emergency physicians should be aware of the possibility of caffeine intoxication in unconsciousness patients with negative drug screening tests. We propose a diagnostic method to help clinicians make a differential diagnosis in such unconscious patients using abdominal CT examination.

Keywords: Caffeine, Intoxication, Abdominal CT, Overdose

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Introduction
Caffeine acts as a phosphodiesterase inhibitor, which increases the concentration of intracellular calcium, causes the release of noradrenaline, and sensitizes the dopamine receptors. These drug actions result in overstimulation of the central nervous and cardiac systems. Ingestion of large quantities of caffeine can be extremely toxic,resulting in tachycardia, arrhythmia, convulsions, vomiting, coma, and death.
Recently, intentional caffeine poisoning by ingestion of tablets has become relatively frequent. Although deaths from caffeine overdose have been increasing, knowledge of caffeine abuse is still limited. In addition, rapid measurement of caffeine concentration in the blood is not always available. Therefore, accurate diagnosis of caffeine intoxication is challenging in the emergency setting if the patient or related people fail to disclose the etiology of overdose caffeine ingestion.
Herein, we describe a case of a 19-year-old boy with caffeine intoxication to share the typical clinical manifestation and therapeutic/diagnostic strategy with emergency physicians. Computed tomography (CT) findings of high-density deposits in the gastrointestinal tract suggested the presence of recently ingested drugs and helped us to suspect overdose. This case report emphasizes the importance of CT as a screening tool for unconsciousness patients and recognizing the typical clinical symptoms of caffeine intoxication to make a differential diagnosis.

Case Report

A 19-year-old man was transferred to our emergency department due to impaired consciousness, vomiting, and tonic-clonic seizures. The patient's family had found him unconsciousness lying on the floor of his house. The patient reported no history of head trauma and denied any seizureprovoking experiences. He had a history of living-donor liver transplantation at 10-years-old, which had been effectively controlled without rejection with administration of tacrolimus 2 mg/day.
On arrival, he was unconscious with a Glasgow Coma Scale score of 5 (E2V1M2). His height and body weight were 167.4 cm and 48.6 kg, respectively. Vital signs included blood pressure 136/86 mmHg, heart rate 106-113 beats per minute, fever of 37.8  degree C, and symmetrically increased deep tendon reflexes. His pupils were 4 mm bilaterally with prompt light reflex. A blood gas analysis showed lactic acidosis (pH 7.012, lactate 7.8 mg/dL). The laboratory data was white blood cells, 21000/μL; hemoglobin 14.6 g/dL; serum creatine kinase, 498 IU/L; sodium 146 mmol/L; potassium, 3.1 mmol/L; blood glucose 96 mg/dL; blood urea nitrogen 12.7 mg/dL; creatinine 0.66 mg/dL; magnesium 1.9 mg/ dL; total bilirubin 0.8 mg/dL; aspartate aminotransferase 32 IU/L; alanine aminotransferase 79 IU/L; and lactate dehydrogenase 506 IU/L.
After sedation and control of seizures with midazolam, intratracheal intubation was required and controlled ventilation was performed, as well as fluid resuscitation with Ringer's solution and prompt stabilization of the patient's cardiovascular status. Electrocardiogram presented supraventricular tachycardia. Tachycardia remained even after fluid resuscitation, administration of amiodarone, and restoration of electrolyte balance. Brain CT and magnetic resonance imaging demonstrated no abnormalities in the intracranial region. Abdominal CT revealed multiple high-density deposits in the gastrointestinal tract, suggesting recently ingested tablets (Figure 1). Although drug screening tests (Triage, Biosite, San Diego, CA, USA) were negative, we assumed that his deteriorated consciousness was attributed to an overdose of undetermined sedative drugs based on the CT findings. His parents had denied any underlying psychiatric disease or history of drug abuse.
However, the following day, his family found an empty bottle of caffeine in the trash. A suicide note was found in his cell phone, in which he purportedly mentioned that he was ending his life. It was assumed that he had ingested approximately 78 caffeine 200 mg tablets (16.5 grams of caffeine). Considering the half-life of caffeine and fair recovery of clinical symptoms, blood transfusion was not performed. Intravenous lipid emulsion was administered as soon as the caffeine ingestion was reported. The blood samples taken at the visit were sent to a reference laboratory to evaluate the concentration of caffeine. The results were positive for caffeine (>50.0 mg/dL). The patient became conscious the following day and reported that he obtained a bottle of caffeine tablets via the internet and ingested the tablets in a suicide attempt. Currently, the patient is well without any neurologic complications.

Discussion

Caffeine is a natural alkaloid methylxanthine extracted from tea leaves, coffee beans, and numerous other plants. It is widely available in beverages such as energy drinks, food, over-thecounter drugs, and herbal and dietary supplements. Caffeine is also a common ingredient in medications, with doses of 30-200mg in many prescription drugs used to treat acute respiratory depression, neonatal sleep apnea, and most commonly headaches and migraines, including intravenous administration for spinal anesthetic-related headache. Thus, caffeine is widely available; however, it has been recognized as an addictive substance and can lead to lethal arrhythmia in large doses. Death from caffeine poisoning, although uncommon, does occur. The direct cause of death is generally ventricular dysrhythmia, although caffeine-related cardiovascular effects are not confined to arrhythmogenesis.
Suzuki et al. emphasized that caffeine intoxication-related deaths mainly occur in young and middle-aged persons with common psychiatric diseases. In half of the cases, the origin of the caffeine was unidentified; nevertheless, dietary sources or over-the-counter drugs containing caffeine were suspected. As it becomes easier to obtain caffeinated products, continuous monitoring of the number of deaths from caffeine intoxication, in addition to detailed investigations of the caffeine's origin, will be necessary [1].
The potential pharmacological effects of caffeine can be explained by three mechanisms of actions: the antagonism of adenosine receptors, the mobilization of intracellular calcium storage, and the inhibition of phosphodiesterases, which increase noradrenaline and sensitize dopamine receptors.
When consumed orally, caffeine is absorbed rapidly and completely. Caffeine undergoes hepatic metabolism, mainly by CYP450 1A2 isoenzyme. Approximately 85% of a dose is excreted in the urine within 48 hours. The plasma half-life is two to 10 hours (mean four hours) in adults. Blood caffeine concentrations within 80-100 mg/L are generally considered lethal in humans, requiring the ingestion of a large quantity of the drug, typically exceeding 5 gram [2]. However, correlations between blood levels and clinical effects are difficult to establish due to individual variability, tolerance, or preexisting disease states.
Treatment consists of oxygen, hydration, paracetamol to control hyperthermia, and sodium bicarbonate for acute
control of acidemia. For seizure control, the patient was initially treated in the emergency room with midazolam infusion with subsequent valproate infusion. Intralipid seems to initially carry the stimulant drug away from the brain and heart to less wellperfused organs [3]. Hemoperfusion has previously been carried out to treat patients with caffeine intoxication [4,5].
Many chemical substances or drugs can be detected in the gastrointestinal tract using plain CT. Also, some toxic substances such as carbon tetrachloride and other chlorinated hydrocarbons are radiopaque and may appear on abdominal X ray [6,7]. The diagnosis of an overdose is usually based on the patient's complaints or a situation with a comatose patient who has a psychiatric disease. However, making an accurate diagnosis of caffeine intoxication can be challenging for such patients without witness of ingestion of overdose of caffeine. We propose a diagnostic method to help with making the differential diagnosis for such unconscious patients using abdominal CT examination [8].

Conclusion

As obtaining caffeinated products becomes easier, caffeine intoxication, sometimes critical and fatal, has been constantly growing, especially among children and youngsters. Although the addictive potential of caffeine has long been reported, awareness about caffeine abuse is still lacking. Our experience suggests the usefulness of CT for making a differential diagnosis in unconsciousness patients. Awareness and recognition of the typical clinical symptoms of caffeine intoxication may be critical in the emergency room.
References
1. Suzuki H, Tanifuji T, Abe N, et al. Characteristics of caffeine intoxicationrelated death in Tokyo, Japan, between 2008 and 2013. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2014;49(5):270-277.
2. Jones AW. Review of Caffeine-Related Fatalities along with Postmortem Blood Concentrations in 51 Poisoning Deaths. J Anal Toxicol. 2017;41(3):167-172.
3. Muraro L, Longo L, Geraldini F, Bortot A, Paoli A, Boscolo A. Intralipid in acute caffeine intoxication: a case report. J Anesth. 2016;30(5):895-899.
4. Ishigaki S, Fukasawa H, Kinoshita-Katahashi N, Yasuda H, Kumagai H, Furuya R. Caffeine intoxication successfully treated by hemoperfusion and hemodialysis. Intern Med. 2014;53(23):2745-2747.
5. Colin-Benoit E, Friolet R, Rusca M, Teta D, Gobin N. Combination of hemodialysis and hemofiltration in severe caffeine intoxication. Nephrol Ther. 2017;13(3):183-187.
6. Bagnasco FM, Stringer B, Muslim AM. Carbon tetrachloride poisoning. Radiographic findings. N Y State J Med. 1978;78(4):646-647.
7. Spiegel SM, Hyams BB. Radiographic demonstration of a toxic agent. J Can Assoc Radiol. 1984;35:204-205.
8. Yanagawa Y, Nishi K, Imamura T, Sakamoto T. Usefulness of computed tomography in the diagnosis of an overdose. Acta Med Okayama. 2011;65:33-39.
Tables & Figures


Figure 1: High-density deposits in the duodenum and small intestine, suggesting an overdose of drug tablets
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