Complications following AER and pathophysiology
Several different physiological theories have been proposed to explain why AER is dangerous, and most of them argue that AER affects afterdrop, a thermodynamic phenomenon. As dictated by the second law of thermodynamics, heat will flow from hot areas to cold areas . In a patient with rapid onset AH, a significant thermal gradient is present between the core and the skin and subcutaneous tissues . As the patient is removed from the cold environment, the thermal energy of the body will seek equilibrium. Heat will travel from the relatively warm core out to the colder, peripheral areas of the body, which results in a drop in the core temperature [25, 26].
A number of theories advocate the physiological dangers of AER, and the most prevalent theory argues that AER will accelerate afterdrop by alleviating peripheral vasoconstriction. Some scientists argue that the flow of blood from the relatively warm core and out through the colder peripheral tissues will increase. They believe this relatively cold blood will return from the extremities and cool the core at a faster rate, and a thermodynamic equilibrium will be instated more rapidly than without the circulatory (convective) component [26,27,28].
Given that the patient is properly isolated and removed from the cold environment, the total thermal energy will not decrease, and the nadir temperature will not be lower if thermal energy is supplied in the form of AER than with passive insulation alone . Therefore, if this theory that AER is dangerous for patients with AH is true, it has to be due to the acceleration of the afterdrop and not an increase of the afterdrop. Both a convective and conductive mechanism is considered relevant, but the exact mechanism is not yet completely understood [27, 29].
Ever since the Napoleonic Wars there has been significant controversy regarding AER, with several authors discouraging this practice. Lankford wrote a very interesting article on the history of cold-related injuries , and James Currie described the phenomenon of afterdrop for the first time . In more recent history, the infamous Dachau experiments conducted by Nazi doctor Sigmund Rascher during the second world war formed the basis for a new understanding of immersion hypothermia. The report of US Major Leo Alexander contained and preserved the results from these atrocities . However, the results and conclusions drawn from these experiments are heavily flawed. A review of the Nazi experiments revealed “critical shortcomings in scientific content and credibility. The project was conducted without an orderly experimental protocol, with inadequate methods, and an erratic execution. The report is riddled with inconsistencies. There is also evidence of data falsification and suggestions of fabrication. Many conclusions are not supported by the facts presented” . Despite the overwhelming criticism of the Dachau experiments, it may seem as though some of the conclusions survived. The Nazi scientists observed a continuous drop in core temperature, and they postulated that this drop in temperature may be responsible for dangerous cardiac arrhythmias.
Since then, many scientific papers have warned about the danger of AER, most of them without citing references [34,35,36,37,38,39,40,41,42,43,44,45]. This may indicate that this theory was sufficiently established as an undisputed truth, even though no scientific evidence supports this.
The articles included in this review, and others that did not meet our specific criteria, report a fairly high mortality rate in patients with AH. It may seem as though the vast majority of deaths occur long after treatment with AER is initiated, or even after the patient is successfully rewarmed [4, 46]. We think that, if the hypothesis of a sudden cardiovascular collapse after AER is true, then the complications should occur fairly soon after the treatment is initiated. It is unreasonable to attribute all of the late deaths from hypothermia to the use of AER, as these deaths are more likely to be a consequence of other pathophysiological mechanisms.
Despite the controversies from old studies, AER is being used in many hospitals today. The fact that we have found only one case published over the last 30 years presenting potential harm from AER would suggest a low risk of complications. In fact, there are numerous articles reporting successful rewarming using AER [47,48,49], and the general consensus among experts seems to be shifting [1, 2, 50,51,52].
This review does not mean to make a conclusion on whether it is safe to use AER in patients with AH. The aim is limited to describing published studies on severe haemodynamic or respiratory complications caused directly by the use of AER. One of the main findings of this review was the low number of articles, and the low quality of those that were found. Relevant cases may not be published because the authors do not believe that it will contribute anything new. Of course, it may also be because the use of AER is not as dangerous as previously perceived.
One specific subgroup may have good reason to be cautious with AER, chronic AH [26, 53]. Chronic hypothermia is most prevalent in the elderly population and can lead to a variety of pathophysiological changes. Shifts in fluid and electrolytes occur that are not immediately reversible and may require more controlled and steady correction [51, 54]. The cold diuresis will have had time to manifest for a prolonged period of time, and the patient may require fluid replacement therapy during rewarming.
A systematic review is considered to be evidence-based science of high quality, summarizing data from multiple randomized controlled trials to synthesize all available knowledge on a specific subject. This review consists mostly of case reports, case series, and small clinical trials with low scientific value. Even though this is a systematic review of the available scientific literature, the quality of the scientific evidence is not as convincing as other systematic reviews. Therefore, the conclusions drawn from this review and the clinical implications must be cautious and reserved.
We chose to exclude all studies involving invasive or extracorporeal techniques of rewarming in their title. However, it is obviously possible that some of the studies advocating the use of invasive warming techniques contain examples of why the use of external warming measures might be dangerous.
Study selection process
During the initial screening for this study, 2200 articles were excluded. There is always a risk that some article titles did not immediately catch our attention and were falsely excluded. Also, 13 articles meeting our search criteria were unobtainable.
Inclusion and exclusion criteria
We chose our inclusion criteria based on what kind of literature we thought would yield the most accurate answer to our research question. However, there may be, for example, animal or laboratory studies available that would have been of interest for this review.