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Study Title and Description

Autopsy report for a caffeine intoxication case and review of the current literature



Key Questions Addressed
1 For [population], is caffeine intake above [exposure dose], compared to intakes [exposure dose] or less, associated with adverse effects on acute toxicity*?
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Primary Publication Information
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TitleData
Title Autopsy report for a caffeine intoxication case and review of the current literature
Author T. Yamamoto, K. Yoshizawa, S. Kubo, Y. Emoto, K. Hara, B. Waters, T. Umehara, T. Murase and K. Ikematsu
Country
Year 2015
Numbers

Secondary Publication Information
There are currently no secondary publications defined for this study.


Extraction Form: Acute Toxicity - Study Design Details
Arms
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Design Details
Question... Follow Up Answer Follow-up Answer
Refid 10523
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What outcome is being evaluated in this paper? Acute
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What is the objective of the study (as reported by the authors)? to present the pathological examination performed in a fatal caffeine intoxication case, along with information on the caffeine concentrations found in the blood, urine, and main organs
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Provide a general description of the methods as reported by the authors. Information should be extracted based on relevance to the SR (i.e., caffeine related methods) autopsy of systemic organs 17 hours after death, fixed in 10% buffered formalin and prepared for routine histopath. Tox analysis of heart blood, urine, gastric contents, brain, lung, heart, liver, kidney, quadricep muscle and skin conducted with caffeine as an internal standard utilized a GC-MS
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How many outcome-specific endpoints are evaluated? 1
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What is the (or one of the) endpoint(s) evaluated? (Each endpoint listed separately) acute toxicity
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List additional health endpoints (separately).
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List additional health endpoints (separately)
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Notes fatality - no alcohol in blood, vitamins were part of supplement that was ingested but authors note 200 mg caffeine/sleep inhibitor
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Clinical Clinical
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Physiological
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Other
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What is the study design? Case report
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Randomized or Non-Randomized?
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What were the diagnostics or methods used to measure the outcome? Both
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Optional: Name of Method or short description measured blood levels of caffeine and in other fluids/organ extracts by GC/MS and used histopath to examine organs as well as gross examination
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Caffeine (general)
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Coffee
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Chocolate
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Energy drinks
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Gum
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Medicine/Supplement Medicine/Supplement
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Soda
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Tea
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Measured Measured
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Self-report
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Children
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Adolescents Adolescents
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Adults
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Pregnant Women
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What was the reference, comparison, or control group(s)? (e.g. high vs low consumption, number of cups, etc.) not applicable as this was a case report- but a caffeine standard was used for GC/MS purposes
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What were the listed confounders or modifying factors as stated by the authors? (e.g. multi-variable components of models.  Copy from methods) not applicable as this was a case report, worth noting that no other drugs were found in the tox report although vitamins were part of the sleep inhibitor that was ingested and that was not mentioned which seems like a confounder in interpretation since vitamins can cause toxicity
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Provide a general description of results (as reported by the authors). analysis indicated no alcohol in blood or urine, large amounts of caffeine in many of the tested samples (heart blood, urine, brain, lung, heart, liver, kidney, quadriceps, skin, gastric contents. External examination revealed no injuries to her body.Large amounts of a gray-white particulate were observed from the mouth to the upper intestine, and there was diffuse bleeding of the gastric mucosa. No abnormalities to heart, brain was edematous.
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Did the authors perform a dose-response analysis (or trend/related analysis)? No
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What were the authors's observations re: trend analysis?
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What were the author's conclusions? Unfortunate-ly we were not able to determine the exact mechanism of death, but we speculated that the brain showed edematous changes, which suggests that death could have possibly been due to respiratory arrest caused by caffeine-induced brain functional damage.
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What were the sources of funding? none reported
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What conflicts of interest were reported? none
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Does the exposure (dose) need to be standardized to the SR? No
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Provide calculations/conversions for the exposure based on the decision tree in the guide (for all endpoints/exposure levels of interest).
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List all the endpoint(s) followed by the dose (mg) which will be used in comparison to Nawrot.  Characterize value as LOAEL/NOAEL, etc. if possible.  acute toxicity (death believed to be due to respiratory arrest that was a consequence of brain edema) dose (effect level) was 51.6g
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Notes regarding selection/listing of endpoints and exposures/doses to be compared to Nawrot. calculation was based on blister packs of the sleep inhibitor and known conc of caffeine reported on the sleep inhibitor of 200mg/tablet X 258 blister packs open/missing believed to be ingested = 51.6 g caffeine (they report 50g). Because this was such a large dose we don't know what level was acutely toxic (the lethal level)
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What is the importance of the study with respect to the adverseness of the outcome? Critcal
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Baseline Characteristics
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Results & Comparisons

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