Hypothermia is a condition defined by a drop in core body temperature below 35ºC (95°F).1 In the prehospital setting, unique conditions such as entrapment can predispose patients to hypothermia.2 As such, prehospital clinicians should be keen to avoid hypothermia if possible, yet also be capable of identifying and treating declines of patient body temperature. For prehospital providers, hypothermia treatments can be rudimentary yet effective. Protecting the patient from further cold exposure is a primary goal.1 Rewarming strategies are debated, but heated blankets, chemical heat packs, and warmed IV fluids are considered beneficial, even if only to prevent further heat loss.1, 3 Often, hypothermia is associated with exposure to cold outdoor environments, but hypothermia can also present in patients found indoors, and patients also present hypothermic during summer months.4, 5

Some studies have also noted increased proportions of “severe” hypothermia cases found indoors when compared to outdoor exposure.4 While approximately 1,500 people have hypothermia listed on their death certificate each year in the United States, the incidence of comorbid hypothermia remains unknown.6 Comorbid hypothermia, however, is not insignificant in its effects on patient outcomes. In patients presenting with trauma, hypothermia is associated with increased hemorrhage risk,7-9 hypovolemia10 and increased mortality.9, 11-15 There is perception in the prehospital field that heated saline is reserved for severe hypothermia cases. However, patient presentations that may have comorbid hypothermia are not uncommon for EMS personnel to encounter, such as trauma and sepsis; this frequency highlights the importance of maximizing hypothermia prevention care, which includes the use of heated saline.1, 16, 17

Issues relating to heat conservation, production, or regulation can lead to hypothermia, and cofactors can include patient age, nutrition, and other comorbid diseases.5 It is further noted that hypothermia can be considered an important clinical marker in patients presenting in a climate-controlled environment, such as a skilled nursing facility.5 There is concern among some providers that heating saline bags can result in bacterial or fungal growth, osmolarity changes, or contamination from plastic breakdown. However, studies have found little to no support for these claims.18-21 As it stands, heated saline’s ability to “fix” hypothermia is questionable, but its ability to stabilize hypothermic patients and improve their outcomes should be emphasized in prehospital care.

Intravenous normal saline solution (NSS) is a widely used IV solution in the U.S. for a variety of conditions. In many prehospital settings, it is the default solution if not the only available option. NSS is often packaged in a flexible PVC bag, which sometimes goes by trade names such as Baxter’s VIAFLEX. This PVC bag then has another overwrap bag, made of a stiffer plastic, which is sealed to enclose the inner, softer PVC bag.22 With this construction, some concerns are raised regarding heating these bags and the saline contained within them for any extended amount of time. An initial concern is that heating the saline solution can create an incubator for bacterial or fungal growth.

A study using heated, room-temperature, and cooled 1L NSS bags showed no signs of fungal or bacterial growth after a period of 199 days, well beyond current recommendations by manufacturers.18 The study also assessed another concern with long-term heating: osmolarity of solution. There is consideration that heating saline bags could potentially increase evaporation rates, concentrating the dissolved salts in a clinically impactful way. After a period of heating for 199 days, no significant deviation in osmolarity was noted.18 Evaporation control is one of the intended purposes of the overwrap, made of stiffer and less porous plastic. Keeping this overwrap intact is key to preventing fluid loss from the bag. While the body of evidence refuting these concerns is certainly not overwhelming, there is not much evidence presented that shows reason for concern. Certainly, more research in this subject would be beneficial to further solidify the actual prevalence of risks.

A final safety concern involves plasticizers. Plasticizers are molecules that are introduced into plastic structures (in this case the crystal structure of PVC) to make stiff plastics into softer, more flexible forms.19 In the case of many medical formulations of PVC, the plasticizer of choice is di(2-ethylhexyl) phthalate, or DEHP.19 Depending on manufacturer, medical PVC formulations can be up to 50% DEHP by weight.19 In the crystal structure, DEHP is held in place with hydrogen bonds, and does not have other covalent bonds stabilizing it.19 Due to the relative weakness and heat sensitivity of hydrogen bonding, the concern for the leaching of DEHP into solution by heating follows logically.

The body of research, however, is not clear cut. A study published in 1973 showed that DEHP levels were insignificant in distilled water, NSS, and 5% dextrose solution after a year of storage in bags made with PVC and DEHP.23 However, significant amounts of DEHP were detected in a surfactant solution, P80, after only 48 hours of storage.23 A further study from 2002 found presence of DEHP in IV tubing, which increased in rate of leeching with temperature, but the experiment only tested a lipid emulsion as its sampled fluid.24 It was noted that a lipophilic solution was used due to DEHP’s increased affinity for lipophilic solutions compared to hydrophilic solutions.24 Thus, the presence in NSS (a hydrophilic solution as opposed to a lipophilic) is not necessarily supported or refuted by these findings.

In 2000, the World Health Organization (WHO) conducted a literature review and classified DEHP as a “Group 3” carcinogen, noting that it was not classifiable in its risk to humans due to insufficient evidence.21 There was, however, evidence of carcinogenicity in animals, namely mice, that were the subjects of multiple studies.21 The mechanism of carcinogenicity involved increased peroxisome proliferation, increasing oxidative stress and leading to cancerous mutations, however, this effect was only seen in mice, and would not occur in humans.21 Later, in 2015, a report reclassified DEHP as a “Group 2B” carcinogen, as having “possible carcinogenicity in humans.”20 This change was spurred by further rodent testing which showed increased rate of reproductive cancers, but these effects were the result of a mechanism not seen in humans.20 The majority of patients, however, are not the main focus of concern for these exposures.

The groups at largest risk are those with either repeated exposures, or large doses compared to body weight. Notably, dialysis patients who have blood exposed to PVC tubing multiple times each week are of greater concern.20 Critical care patients who require ECMO and neonates are of increased concern as well due to larger doses as a result of large exposures of blood to PVC tubing and smaller body weight, respectively.20 With this in mind, DEHP has potential for long-term concern, however it is important to weigh the risks and benefits of any treatment. For patients receiving IV fluids in an out-of-hospital scenario, the indications for such a treatment are often acute needs, with the intention of rectifying life threats. As will be discussed below, heating IV fluids before administration can also improve outcomes in a number of patients. When this is compared to the risk of potential exposure to a potential carcinogen, the clinical benefits are apparent.

The treatment of hypothermia is subject to mild debate as ongoing research assesses which methods are effective. For many clinicians, heated saline seems like a natural rewarming approach for hypothermic patients, but some studies suggest that this treatment may not be the silver bullet it appears to be.25, 26 When compared to patients who were rewarmed by shivering alone, heated IV NSS was not shown to significantly improve rewarming times.26 From a thermodynamic perspective, two liters of NSS amounts to approximately 4% of the body’s total water, which is why heating the saline may not have a massive effect on rewarming speed.26 This is not to say, however, that heating saline is useless for hypothermia treatment. For patients receiving large amounts of fluid, preheating the saline avoids a further drop in body temperature, and reduces physiologic stress on the patient.1, 16, 17, 25

Hypothermic patients also experience a “cold diuresis” due to systemwide vasoconstriction, which leads to hypovolemia as they rewarm.16, 25 Providing heated saline during this process helps rectify this hypovolemia while simultaneously helping stabilize body temperature.16, 25, 27 In patients who are at risk for hypothermia, a Cochrane Review of over 1,200 patients undergoing surgery found a significant improvement in core temperature maintenance when heated IV saline was administered, compared to room temperature saline.28 Heating IV saline may not act as a standalone rewarming method, but the benefits it provides for stabilizing body temperature and improving hypovolemia associated with hypothermia are notable.

While heated saline may seem reserved for isolated hypothermia treatment alone, current research suggests that it may have benefits for multiple other pathologies more commonly seen in out-of-hospital care. In trauma patients, hypothermia is associated with multiple negative sequelae, such as a breakdown of the clotting cascade and other associated factors.7, 9 It is also found that hypothermia is more resultant from the shock seen in trauma patients as opposed to a metabolic insufficiency.9 There is a noted proportionality of rates of hypothermia and severity of injury in trauma patients, however through all injury severity levels hypothermia is associated with increased mortality.11-13 This effect is so pronounced that early reviews placed any trauma patients with core temperatures under 32ºC in the “unsalvageable” category.13 Further reviews did find patients under 32ºC to be salvageable, but still found the same trend of increasing mortality rates as core temperature decreased among trauma patients, with an increase in mortality up to 11 times above normothermic patients.14 A review of over 400,000 pediatric trauma patients also found that hypothermia was associated with increased mortality, as well as a higher likelihood of intubation and requiring blood transfusion.12

Another study found that after arrival to the emergency room, patients presenting with hypothermia were noted to have twice the mortality of normothermic patients, both at 24 hours and 28 days after presentation.29 A study involving mice induced into varying stages of hypothermia noted an increase of 18% in survival rates when active rewarming using IV fluids was performed as opposed to passive rewarming.30 The same study also noted decreased rates of infection of surgical sites when active rewarming and antibiotics were used, as opposed to passive rewarming and the same antibiotic regimen.30 Other critical patient populations see benefit from treatment and avoidance of hypothermia as well, namely sepsis patients. Studies focusing on sepsis have found that 6-8% of patients are noted to have hypothermia at triage, and hypothermia is associated with significantly higher mortality rates.31, 32

A meta-analysis of forty-two studies found that among the over 10,000 patients studied, lower body temperatures were associated with higher mortality as compared to normothermic patients.33 Hypothermia in sepsis patients is also associated with a higher rate of arrival by EMS, and longer hospital stays in addition to increased mortality,34 highlighting the importance of prehospital recognition and treatment. As a final consideration for other patients that require NSS, patient comfort has been rated much higher with heated saline as compared to room temperature saline in double blind studies.35 A multitude of small studies corroborate each other, showing reduced shivering and reduced patient discomfort when heated saline is used.36-39

Heating IV saline has long been seen as an optional procedure reserved for wintertime treatment of hypothermia. However, hypothermia can present itself year-round, and causes can include pathological etiologies in addition to environmental ones. While safety concerns may exist regarding heating NSS, the evidence does not show distinct risks to patients in all but specific cases, those of which are rarely seen or applicable in prehospital care. As for the benefits to patients, heated saline may not be a definitive cure for hypothermia, but its treatment of hypovolemia and improved ability to prevent further hypothermia merit consideration from clinicians.

In patients commonly seen in out-of-hospital care, such as trauma and sepsis, the prevention of hypothermia can have significant impacts improving patient mortality. Even in non-critical patients, the use of heated saline can improve patient comfort, reducing the overall stress experienced by prehospital patients. In terms of patient comfort and outcomes, the use of heated saline over room temperature saline has apparent benefit and should be considered where possible; however, further investigation is needed to better elucidate heated saline’s role in patient care.

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20. Testai E, Ms Scientific Committee SEaS-CSeee, Hartemann P, Rastogi SC, Bernauer U, Piersma A, et al. The safety of medical devices containing DEHP plasticized PVC or other plasticizers on neonates and other groups possibly at risk (2015 update). Regul Toxicol Pharmacol. 2016;76:209-10. Epub 2016/02/09. doi: 10.1016/j.yrtph.2016.01.013. PubMed PMID: 26854686.

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