To the editor,
We have read the article titled “Characteristics and Outcome of Exertional Heatstroke Patients Complicated by Acute Hepatic Injury: A Cohort Study” by Ji et al.1 We congratulate the authors for this insightful article. In this letter, we would like to raise several issues about the article to provide constructive criticisms.
Heatstroke involves a systemic inflammatory response, the full damage of which is not only limited to the hepatobiliary system. Instead, it can also cause damage to other organ systems, including the central nervous system, cardiovascular system, gastrointestinal system, hematological system, and immune system.2 However, the authors do not seem to weigh multiple organ failure following heatstroke. This can be misleading to the readers, who may believe that development of acute liver failure (ALF) is common in patients with heatstroke. Bi et al.3 reported that exertional heatstroke uncommonly progresses to ALF; therefore, ALF secondary to heatstroke is rare. Additionally, the authors define acute hepatic injury simply as a coagulopathy with the elevated international normalized ratio (INR), to which we cannot agree. Lack of sweat and impaired heat dissipation would represent hypovolemic conditions that increase blood viscosity and the risk of thrombosis leading to microvascular hypoperfusion.4 During the coagulation response in heatstroke, hyperthermia typically occurs, damaging vascular endothelium and inducing microthrombosis and fibrin formation—the disseminated intravascular coagulation may clinically manifest.5 Secondly, the authors seem to underestimate the significance of brain injury in the patients with severe heatstroke, evidenced by the use of the Glasgow Coma Scale only for evaluation in their study. According to Hifumi et al.,2 brain injury in heatstroke can cause severe cerebral edema, an essential indicator of neurologic sequelae and death. Using an imaging modality, such as brain CT and MRI, should be considered for evaluating brain edema as a severity index of heatstroke.6 Finally, we think that the criteria used for the infection group were inappropriate, i.e. procalcitonin elevation > 2 ng/mL and white blood cell count > 10×109 /L. Heatstroke is known as a systemic inflammatory syndrome that results in a sepsis-like condition.7 The permeability of gastrointestinal epithelia may increase due to damaged tight junctions and cell membranes during the state of hyperthermia, splanchnic hypoperfusion, and hypoxia.8 Subsequently, the barrier dysfunctions in the gastrointestinal tract tend to result in the translocation of bacterial endotoxin or complete microorganisms from the intestinal epithelium to the bloodstream that may favor the occurrence of a systemic inflammatory response.9,10 These inflammatory mechanisms can lead to elevated serum procalcitonin levels in the patients but without evidence of bacterial infection.11 However, among the typical heatstroke patients, the association between elevated serum procalcitonin level and bacterial infection is not clear. Therefore, the authors’ criteria for the infection group are misleading in that elevated procalcitonin level alone does not indicate the infectious state and is not a risk factor for mortality in heatstroke.
We hope that our clarification would assist the readers in obtaining a correct understanding of the essential roles of the liver in the development of heatstroke.
Declarations
Funding
None to declare.
Conflict of interest
The authors have no conflict of interests related to this publication.
Authors’ contributions
Study design (SC, HK), drafting of the manuscript (HY), revision of the manuscript (SC, HY). All authors approved the final version of the manuscript.