Acetaminophen/diphenhydramine overdose in profound hypothermia

Rollstin, Amber; Seifert, Steven A.

doi:10.3109/15563650.2012.748195

Cited by 19 publications

(8 citation statements)

References 10 publications

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“…The effect of APAP on non-febrile temperature regulation has been investigated previously in mice ( Ayoub et al, 2004 ; Li et al, 2008 ; Ayoub et al, 2011 ; Gentry et al, 2015 ) and humans ( Kasner et al, 2002 ; Dippel et al, 2003b ; den Hertog et al, 2009 ). There are also reports of severe hypothermia (T C = 28°C on hospital admission) following acute APAP overdose ( Rollstin and Seifert, 2012 ). Prior to the present work, this potentially hazardous side-effect had not been confirmed in passive, nutritionally controlled participants or conducted in a temperature controlled environmental chamber.…”

Section: Discussionmentioning

confidence: 99%

Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans

et al. 2016

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In non-febrile mouse models, high dose acetaminophen administration causes profound hypothermia. However, this potentially hazardous side-effect has not been confirmed in non-febrile humans. Thus, we sought to ascertain whether an acute therapeutic dose (20 mg⋅kg lean body mass) of acetaminophen would reduce non-febrile human core temperature in a sub-neutral environment. Ten apparently healthy (normal core temperature, no musculoskeletal injury, no evidence of acute illness) Caucasian males participated in a preliminary study (Study 1) to determine plasma acetaminophen concentration following oral ingestion of 20 mg⋅kg lean body mass acetaminophen. Plasma samples (every 20 min up to 2-hours post ingestion) were analyzed via enzyme linked immunosorbent assay. Thirteen (eight recruited from Study 1) apparently healthy Caucasian males participated in Study 2, and were passively exposed to 20°C, 40% r.h. for 120 min on two occasions in a randomized, repeated measures, crossover design. In a double blind manner, participants ingested acetaminophen (20 mg⋅kg lean body mass) or a placebo (dextrose) immediately prior to entering the environmental chamber. Rectal temperature, skin temperature, heart rate, and thermal sensation were monitored continuously and recorded every 10 min. In Study 1, the peak concentration of acetaminophen (14 ± 4 μg/ml) in plasma arose between 80 and 100 min following oral ingestion. In Study 2, acetaminophen ingestion reduced the core temperature of all participants, whereas there was no significant change in core temperature over time in the placebo trial. Mean core temperature was significantly lower in the acetaminophen trial compared with that of a placebo (p < 0.05). The peak reduction in core temperature in the acetaminophen trial was reached at 120 min in six of the thirteen participants, and ranged from 0.1 to 0.39°C (average peak reduction from baseline = 0.19 ± 0.09°C). There was no significant difference in skin temperature, heart rate, or thermal sensation between the acetaminophen and placebo trials (p > 0.05). The results indicate oral acetaminophen reduces core temperature of humans exposed to an environment beneath the thermal neutral zone. These results suggest that acetaminophen may inhibit the thermogenic mechanisms required to regulate core temperature during exposure to sub-neutral environments.

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Section: Discussionmentioning

confidence: 99%

Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans

et al. 2016

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“…15,17–19 To date, no large-scale studies have examined differences in clinical presentation or clinical outcomes of APAP combination compounds. 15,16,20 …”

mentioning

confidence: 99%

Risk Factors, Clinical Presentation, and Outcomes in Overdose With Acetaminophen Alone or With Combination Products

Serper

Wolf

Parikh

et al. 2016

Journal of Clinical Gastroenterology

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Background and Aims Acetaminophen (APAP) is the most common cause of acute liver failure (ALF) in the west. It is unknown if APAP overdose in combination with diphenhydramine or opioids confers a different clinical presentation or prognosis. Study objectives were to compare (1) baseline patient characteristics; (2) initial clinical presentation; and (3) clinical outcomes among patients with ALF due to APAP alone or in combination with diphenhydramine or opioids. Methods We analyzed 666 cases of APAP-related liver failure using the Acute Liver Failure Study Group database from 1998 to 2012. The database contains detailed demographic, laboratory, and clinical outcome data, including hemodialysis, transplantation, and death and in-hospital complications such as arrhythmia and infection. Results The final sample included 666 patients with APAP liver injury. A total 30.3% of patients were overdosed with APAP alone, 14.1% with APAP/diphenhydramine, and 56.6% with APAP/opioids. Patients taking APAP with opioids were older, had more comorbidities, and were more likely to have unintentional overdose (all P < 0.0001). On presentation, 58% in the APAP/opioid group had advanced encephalopathy as compared with 43% with APAP alone (P = 0.001) The APAP/diphenhydramine group presented with the highest serum aminotransferase levels, no differences in laboratory values were noted at 3 days postenrollment. No significant differences were observed in clinical outcomes among the groups. Conclusions Most patients with APAP-induced ALF were taking APAP combination products. There were significant differences in patient characteristics and clinical presentation based on the type of product ingested, however, there were no differences noted in delayed hepatotoxicity or clinical outcomes.

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“…The efficiency in which PGE 2 (via EP 3 receptor activation in the POA) raises T C during fever would make this a useful mechanism for humans to defend their T C in cold environments or environments set beneath the TNZ. This theory is supported by evidence in animal models [21,[35][36][37], and humans [38][39][40][41][42], whereby COX inhibitors (and thus reduced PGE 2 synthesis) have been shown to cause dose dependent T C reductions in the absence of fever or immune response (afebrile). In the following sections, afebrile animal and human studies that have used COX/PGE 2 inhibitors during cold stress, and its effect on T C regulation, will be discussed.…”

Section: Evidence For Afebrile Pge 2 Mediated Thermogenesismentioning

confidence: 89%

“…In that pilot work [42], participants were passively exposed to 20°C wearing only shorts, which is beneath the human TNZ [49,53]. Finally, a recent case report showed that a 37 year old female presented at accident and emergency with a T C of 17°C, 19 h post ingestion of $50 g oral ACT (overdose) [54]. Based on the evidence presented in the current work, it is possible that ACT mediated PGE 2 blockade rendered the patient incapable of normal thermoregulation, an effect which may have been exacerbated if the patient collapsed in an environment beneath the TNZ.…”

Section: Human Modelsmentioning

confidence: 99%

Is prostaglandin E2 (PGE2) involved in the thermogenic response to environmental cooling in healthy humans?

et al. 2015

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Acetaminophen/diphenhydramine overdose in profound hypothermia

Cited by 19 publications

References 10 publications

Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans

Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans

Risk Factors, Clinical Presentation, and Outcomes in Overdose With Acetaminophen Alone or With Combination Products

Is prostaglandin E2 (PGE2) involved in the thermogenic response to environmental cooling in healthy humans?

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