ReviewThe impact of hypothermia on serum potassium concentration: A systematic review
Introduction
Primary accidental hypothermia accounts for almost 1500 deaths per year in the United States [1]. Cardiac arrest (CA) can occur at body temperatures under 30 °C [2]. It is generally associated with better outcome as compared with asphyxia or trauma-related CA [3].
Distinguishing hypothermia-related CA from non-hypothermic CA is challenging. A potassium cut-off at 8 mmol/L for patients in accidental hypothermia is used in the decision-making process on whether or not to start extracorporeal life support (ECLS) rewarming [2], [4]. Hyperkalaemia is an indicator of hypoxic cell death [5] and an increase of 2 mmol/h following exitus has been reported [6]. Other reasons to withhold ECLS in these patients are death by hypoxia with an non-patent airway, a burial time less than 60 min, a body temperature over 30 °C or lethal injuries [7], [8]. Elevated arterial lactate concentration, low pH level and coagulation disorder have also been described as prognostic factors in accidental hypothermia but no specific threshold were validated for ECLS rewarming indication [9], [10]. The current guidelines are referring the serum potassium concentration as the only valid prognostic biomarker for decision-making in ECLS-rewarming [2].
While the potassium level in accidental hypothermia is generally expected to increase, hypokalaemia is a frequent complication of therapeutic hypothermia [11], [12], [13] and clinical studies have shown a decrease in the potassium rate as the patient becomes hypothermic [14], [15]. Experimental studies have also proven hypokalaemia upon the induction of hypothermia, concluding that the absence of trauma and ischaemia in pure hypothermia instead produces a decrease in measured serum potassium [16], [17].
In contrast to this observation, there are some findings of cold exposure presenting hyperkalaemia despite the absence of causes other than hypothermia [18].
In a recent study by Cohen et al, a lower threshold of 4.35 mmol/L serum potassium was associated with 100% specificity to predict brain anoxia on brain CT scan in hypothermic cardiac arrest [19]. These results suggest a relationship between any elevation of potassium level and cellular lesion in the specific context of deep accidental hypothermia.
We aimed to systematically review the pathophysiological implications of hypothermia and its impact on blood potassium levels and thereby facilitate clinical interpretation for triage toward ECLS rewarming in hypothermia-related CA.
Section snippets
Identification and protocol
A systematic review of the literature was conducted following the PRISMA Guidelines for systematic reviews [20].
Eligibility criteria
The Medline electronic database was searched on 28.12.2016 via PubMed for articles published from January 1970 to December 2016. No restrictions for the study type were imposed and all types of studies were considered. Only articles in English, French or German were selected.
Information sources and search strategy
The MEDLINE search strategy was developed by a member of the project team (SB). The search concepts included
Study selection
The search strategy allowed 115 studies to be assessed for eligibility (Fig. 1). An additional eight studies were identified by checking the references of located, relevant papers and searching for studies that had cited these papers. Finally, 50 studies met the inclusion criteria and were included in the systematic review (see Fig. 1. PRISMA flow diagram).
Study characteristics
The different types of studies selected for the review are presented in Table 3. The results are summarised in Table 4 providing an overview
Discussion
To our knowledge, this is the first systematic review to provide insight into the pathophysiological consequences of hypothermia on the potassium rate. Understanding this relationship is of particular importance in clinical practice to manage patients with hypothermia-related cardiac arrest. Our results highlight that initially hypothermia by itself results in hypokalaemia; however, it will not prevent but only delay the rise of potassium levels [4], [17]. Therefore, the question to be asked
Limitations
This review included a number of studies in the LOE P5 category. This can be explained by the high proportion of experimental studies used for this review. It is difficult to assess pure hypothermia in human beings since the potential danger of this intervention is unethical and not warranted by the possible scientific gain. Therefore, we were obliged to extract a majority of the information from animal models.
The quality of the studies was equally assessed according to the standards of good
Conclusion
The initial response to hypothermia seems to be a decrease in potassium levels owing to an intracellular shift. Possible reasons are liver pooling of potassium and membrane stabilisation in hypothermia effecting specialised temperature-sensitive K+ channels. The effect is most likely an accumulation of many factors but in order to outline the primary cause further research is needed.
Subsequently, the final stage of hypothermia can lead to hyperkalaemia, indicating irreversible cell damage.
Conflicts of interest
The authors have no conflict of interest to declare.
This research has received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. No sponsor was involved in the study protocol development and did not have any role in the conduct of the systematic review, data analysis and interpretation, or publication of the results.
Acknowledgment
We would like to thank Valerie Descombe for her participation in data acquisition. Parts of the study constitute the topics of the medical thesis of Sarah Buse.
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