TY - JOUR
AU - MD, Charles S. Cox, Jr.,
AB - ABSTRACT Hypothermia increases mortality rates and should be treated aggressively in the forward echelons of care, but no practical solution exists to accomplish such treatment. The enormous energy burden for this task requires maximal thermodynamic efficiency for a practical portable solution. This review article presents an overview of the clinical and thermodynamic challenges related to the development of a successful system for treatment of hypothermia in the forward echelons. Specific issues addressed include (1) the clinical and logistical reasons why thermal resuscitation should be attempted at all in such a difficult environment, (2) the thermodynamic reasons why warm intravenous fluids, although helpful in not worsening hypothermia, cannot safely transmit enough energy to treat established hypothermia, (3) which among the various methods of rewarming are most likely to result in successful therapy, and (4) the energetic considerations that dictate that any practical portable solution to the treatment of hypothermia must use hydrocarbon combustion as the source of heat. INTRODUCTION Hypothermia remains a prevalent clinical problem. Trauma surgeons are in general agreement that hypothermia needs to be treated aggressively in injured patients, but the combat and evacuation environments favor the establishment of hypothermia in combat wounded even in warm climates. The lack of an available forward-echelon solution to hypothermia reflects the difficulty of the problem, attributable in large part to the fact that civilian warming apparatuses are poorly suited to the modern nonlinear battlefield. To establish the parameters for a successful forward-echelon solution to the problem of hypothermia, this review examines the following questions. (1) Why does hypothermia need to be aggressively treated in the difficult forward surgical environment? (2) Which of the many available patient-warming strategies is the appropriate choice for field rewarming? (3) How can such a strategy be implemented to maximize the mobility and logistical efficiency of a rewarming system, such that normothermia can be achieved as soon after injury as possible and can be maintained? WHY TREAT HYPOTHERMIA IN THE FORWARD ENVIRONMENT? Hypothermia is known to worsen both shock1,–3 (Fig. 1) and bleeding.4,–6 These effects combine dramatically to increase mortality rates in major injuries.7,–9 One large, civilian, registry-based study suggests that a core temperature of ≤35°C defines a group whose mortality rate is at least 8 times higher than that of subjects who remain normothermic10 (Fig. 2). FIGURE 1. View largeDownload slide Effect of increasing core temperature on oxygen delivery, the endpoint of trauma resuscitation. The study focused on hypothermia for isolated brain injury and did not account for the additive deleterious effects of hemorrhagic shock and major injury, which would impair oxygen delivery in hypothermia.3 FIGURE 1. View largeDownload slide Effect of increasing core temperature on oxygen delivery, the endpoint of trauma resuscitation. The study focused on hypothermia for isolated brain injury and did not account for the additive deleterious effects of hemorrhagic shock and major injury, which would impair oxygen delivery in hypothermia.3 FIGURE 2. View largeDownload slide Mortality rate at each admission body temperature. Body temperature was rounded to the nearest integer (N = 700,304 patients, from the National Trauma Data Bank [NTDB]).10 FIGURE 2. View largeDownload slide Mortality rate at each admission body temperature. Body temperature was rounded to the nearest integer (N = 700,304 patients, from the National Trauma Data Bank [NTDB]).10 Causes of Hypothermia in the Forward Echelons Hypothermia develops from several factors in trauma. Body heat is convectively lost to the environment, and this effect is worse with bleeding or the presence of large-surface area burns. The body loses both central thermoregulation and peripheral shivering after traumatic injury.11 Less heat is produced peripherally as perfusion decreases in shock.4 The prolonged evacuation times of the nonlinear battlefield put wounded at increased risk for developing hypothermia. After evacuation, the austere echelon 2 environment puts casualties at risk for more hypothermia. After resuscitation, further evacuation generally ensues by airlift, which results in modern casualties being subjected to repetitive bouts of hypothermia, with associated tissue ischemia-reperfusion injury. The severely wounded for whom echelon 2 units deploy most of their resources are the most likely to become hypothermic. Among such casualties, those who undergo surgery are at greatest risk. The forward operating room has limited environmental control to prevent heat loss during surgery, when heat loss is greatest.12 The development of hypothermia and coagulopathy limits the duration of “damage control” operations even in climate-controlled civilian trauma centers; the lack of thermal support imposes severe limits on what can be accomplished surgically in echelon 2. Faster Warming Is Clinically and Logistically Important Among recognized methods for warming hypothermic patients, direct delivery of heat into a central vein is by far the most efficient method of heat transfer (Fig. 3). Therefore, any solution to the problem of hypothermia that uses a method other than central (core) rewarming necessarily is logistically wasteful, because of radically reduced efficiency. FIGURE 3. View largeDownload slide Thermodynamic comparison of available warming methods. Each plot represents the theoretical best performance for the technique.23 The theoretical curves for CAVR and forced-air warming very closely reflect the clinical data shown in FIGURE 4. circ, Circulation; IV, intravenous. FIGURE 3. View largeDownload slide Thermodynamic comparison of available warming methods. Each plot represents the theoretical best performance for the technique.23 The theoretical curves for CAVR and forced-air warming very closely reflect the clinical data shown in FIGURE 4. circ, Circulation; IV, intravenous. Continuous core heat delivery may be achieved through infusion of any warmed solution into a central vein. Efforts in this realm have been focused on one of two methods, that is, infusion of heated crystalloid solutions and high-flow continuous blood warming. Continuous arteriovenous rewarming (CAVR) was compared with “standard” rewarming (warm intravenous fluids plus forced-air warming blanket) in a randomized controlled trial.13 Relevant findings from the trial are shown. Figure 4 shows that the thermodynamic predictions with regard to rewarming efficiency were reproduced clinically. Although it was not the primary outcome measure in that study, the impact on survival rates is shown in Figure 5. CAVR resulted in a higher early survival rate (p = 0.047), but this trend lost significance when late death was considered (survival rate of 66% with CAVR, compared with 50% with standard rewarming; p = 0.24). Indeed, this treatment effect occurred entirely in the first 20 hours, which suggests that active thermal resuscitation can directly interrupt the “bloody vicious cycle” of hypothermia, acidosis, and coagulopathy. This notion is reinforced by Figure 6, which shows the difference in blood transfusion requirements between the two groups. Preservation and transport of blood products constitute a major logistical burden. The difference in blood transfusion requirements occurred entirely in the first 4 hours in that study, which suggests that intervention in the forward echelons has a dramatic impact not only on survival rates but also on weight, space, and refrigeration in the transport of resuscitation resources. Therefore, treatment of hypothermia in the forward echelons of care is likely both to improve outcomes and to lessen the overall logistical burden related to casualty care. FIGURE 4. View largeDownload slide Results of a clinical trial comparing standard rewarming (SR) and CAVR. Standard rewarming used warm intravenous fluids and a forced-air warming blanket. Normothermia was achieved much more quickly with CAVR.24 FIGURE 4. View largeDownload slide Results of a clinical trial comparing standard rewarming (SR) and CAVR. Standard rewarming used warm intravenous fluids and a forced-air warming blanket. Normothermia was achieved much more quickly with CAVR.24 FIGURE 5. View largeDownload slide Survival curves for standard rewarming (SR) and CAVR. Survival was more likely when trauma victims were resuscitated through CAVR.13 FIGURE 5. View largeDownload slide Survival curves for standard rewarming (SR) and CAVR. Survival was more likely when trauma victims were resuscitated through CAVR.13 FIGURE 6. View largeDownload slide Blood product requirements for standard rewarming (SR) and CAVR. Blood product requirements were much lower when normothermia was achieved quickly, through CAVR.24 The savings in blood occurred in the first 4 hours of resuscitation, which indicates that rapid rewarming is desirable. FIGURE 6. View largeDownload slide Blood product requirements for standard rewarming (SR) and CAVR. Blood product requirements were much lower when normothermia was achieved quickly, through CAVR.24 The savings in blood occurred in the first 4 hours of resuscitation, which indicates that rapid rewarming is desirable. How Much Energy Is Required for Rewarming in Hypothermia? The answer to this question is critical to any meaningful consideration of possible solutions to the warming problem; in fact, the energy requirement for rewarming a patient, ERW, is large enough to eliminate nearly all standard technologies from consideration. The bulk of thermal mass in humans comes from our large water content. It can be assumed that a 70-kg warfighter has ∼50 kg of water. At an initial core temperature of 32°C, 250 kcal are required to achieve nor-mothermia. It should be noted that this value assumes perfect heat transfer efficiency and no energy requirement for warming the solid portions of the body; therefore, the actual requirement would be significantly larger. A casualty is in a complex thermal equilibrium with his or her surroundings. Metabolic heat production and storage are balanced by losses from evaporation, convection, and radiation; the losses, in turn, are affected by considerations such as clothing, external temperature, and wind speed. Also, heat transfer within humans occurs primarily through the bloodstream (as opposed to direct conduction). Although solutions to this highly complex system for wounded soldiers in a combat environment are not extant, a very conservative estimate is a loss to the environment of 1 kcal/minute.14 Because overall heat transfer is limited by the need to avoid thermal injury to tissue, warming must occur over a finite time interval. Choosing 100 minutes as the warming interval yields a minimal value of 350 kcal for rewarming a hypothermic casualty. This value underestimates the true requirements in the vast majority of actual casualty situations, especially if exogenous fluids are being administered. Warmed Intravenous Fluids Alone Cannot Treat Established Hypothermia Because the infusion of cold intravenous fluids induces hypothermia in casualties, a logical adjunct to casualty resuscitation has been the use of civilian fluid warmers to lessen this injury. This practice has led to the commonly held misconception that a hypothermic casualty can be rewarmed by the same means. However, it is energetically impossible to resuscitate a hypothermic casualty with warmed intravenous fluids. If V represents the total volume of fluid (in liters) required to deliver a given amount of heat energy, then V =ERW/∈IVF, where ERW is the energy required to rewarm the patient and ∈IVF is the average energy available for transfer in 1 L of crystalloid solution. If the infused fluid temperature, TFL, is constant, then the average heat energy (in kilocalories) available per liter for transfer to the patient is expressed as ∈IVF = TFL − (TSTART + TEND)/2. Assuming ERW = 350 kcal, TSTART = 32°C, and TEND = 37°C and substituting into the first equation allows the volume V to be expressed in terms of the infused crystalloid solution temperature, TFL. These results are shown graphically in Figure 7. FIGURE 7. View largeDownload slide Curve showing that warmed crystalloid solution cannot rewarm a hypothermic casualty. The curve shows how much fluid is required, based on the temperature of the infused fluid. Warming at 60°C, the maximal purported safe infusion temperature, requires 14 L. This is well over the limit known to induce abdominal compartment syndrome and acute respiratory distress syndrome. FIGURE 7. View largeDownload slide Curve showing that warmed crystalloid solution cannot rewarm a hypothermic casualty. The curve shows how much fluid is required, based on the temperature of the infused fluid. Warming at 60°C, the maximal purported safe infusion temperature, requires 14 L. This is well over the limit known to induce abdominal compartment syndrome and acute respiratory distress syndrome. Data in a canine experimental model,15 as well as limited clinical data from burn patients,16 suggest the possibility of infusion of crystalloid solution at 55°C to 60°C into a central vein. Each 1 L of “overheated” intravenous fluid would contain an average of ∼25 kcal of deliverable heat. Such a resuscitation would require infusion of 14 L, still well over twice the amount known to induce both acute respiratory distress syndrome and abdominal compartment system.17 Anecdotal reports suggest that peripheral veins are less tolerant of such overheated intravenous fluid infusion.18 WHAT IS THE RIGHT WAY TO RESUSCITATE A HYPOTHERMIC CASUALTY? Because all energy required to warm a casualty must be transported forward, the most energy-efficient heat-transfer method makes the most logistical sense. Also, the most efficient method would necessarily warm the casualty faster than any other technique, thus limiting the extent of ischemia/reperfusion injury associated with hypothermia. Finally, whatever method is chosen should be able to accompany the casualty throughout the evacuation chain, so that hypothermia does not recur during a cold helicopter evacuation. Currently Known Warming Methods A multitude of different methods have been devised to transfer heat into a hypothermic patient. These methods may be classified as external methods, which transfer heat across the patient's skin, and internal methods, which deliver heat into a body cavity or into the vascular system. The various methods were modeled from a thermodynamic standpoint to demonstrate the theoretical best performance for each method.19 The results of that study are summarized in Figure 3. As is apparent from the graphs for radiant warmers and forced-air warming blankets, the thermal transfer efficiency of external methods is severely limited by the thermal conductivity of the skin. Also of note, external methods require patients to become more hypothermic before they begin to warm up; this period reflects the time required for skin arterioles to dilate and to begin to receive external heat. Warming blankets prevent access to the casualty for necessary procedures and, as a logistic concern, these methods waste significant amounts of energy through convection. One method of enhancing thermal transmission from an external heat source involves the application of negative external pressure to an extremity to dilate peripheral vessels. This method has been shown to reduce warming times in mild hypothermia after anesthesia for elective surgery.20 Thermodynamically, this method reduces the time required for skin arterioles to dilate and thus reduces overall warming time. The heat transfer rate, however, is still limited by the ability of the skin to transmit heat without injury. Also, peripheral vasoconstriction is a protective response to maintain blood pressure in hemorrhagic shock; the hemodynamic effect of intentional peripheral vasodilation in such a patient is unknown. Internal methods involve either body cavity lavage or direct infusion of heated fluid into the vascular system. Cavity lavage requires the placement of large-bore chest tubes, through which heated fluid is infused into the pleural space and then drained. It is intuitively obvious that a method that requires fluid exchange would transfer energy more slowly than a method in which heat is transferred continuously, and this notion is demonstrated clearly in Figure 3. Continuous Central Blood Warming Is the Most Rapid Warming Method From a thermodynamic standpoint, it makes no difference whether the fluid infused is blood or saline solution. Therefore, the same thermal transfer efficiency can be achieved by removing the patient's blood, warming it, and then reinfusing it. Continuous core blood warming, in addition to using the most thermodynamically favorable heat transfer route, also requires no unnecessary intravenous fluid to be administered. This both reduces the incidence of organ failure and decreases the logistical need to transport intravenous fluid. Some considerations may limit the application of high-flow core blood rewarming in the far-forward environment. Specifically, echelon 2 facilities may not always have the resources, time, or other capabilities necessary for the placement of large central venous or arterial cannulae. Also, the use of a large-bore arterial catheter in CAVR is associated with a risk of limb ischemia; this and other complications of central vascular access may be difficult to manage in echelon 2. HOW CAN HIGH-FLOW CENTRAL REWARMING BE PERFORMED IN ECHELON 2? Heating fluid is simple. Providing the energy necessary for complete resuscitation in a portable package is exceedingly difficult, because water has such a high heat capacity. This is perhaps best illustrated by Figure 8, which shows the relative power requirements of items that might be found in an Army forward surgical team. FIGURE 8. View largeDownload slide Relative electrical power requirements for items found in a forward surgical team operating room. The fluid warmer draws as much power as everything else combined. FIGURE 8. View largeDownload slide Relative electrical power requirements for items found in a forward surgical team operating room. The fluid warmer draws as much power as everything else combined. The effectiveness of civilian fluid-warming systems in the forward area is primarily limited by size and power requirements,21 because these systems invariably require generated electricity as the energy source for fluid warming. The level 1 fluid-warming system is by far the largest generator drain of typical echelon 2 equipment (Fig. 8). Several possible choices exist for the energy source to heat medical fluids. Most, however, simply are not useful for a portable system. The relevant characteristic of a fuel source for this purpose is energy density, that is, the amount of energy contained per unit mass. Whatever the energy source, a certain amount of heat must be transferred into a fluid to achieve the desired infusion temperature. Electricity Is Too Heavy for a Portable Fluid Warmer A portable hypothermia solution by definition cannot be bound to generated electricity, or the casualty will become hypothermic during transport or in any situation where sufficient generator capacity is not available. Rechargeable nickel cadmium batteries are the technology of choice for high-current applications such as heat generation. This cell type can supply ∼50 cal/g of battery mass before recharging is required. Even assuming unrealistic efficiency, this means that a 7-kg battery pack would be required to provide the necessary 350 kcal of energy (with none left over to maintain normothermia). This analysis is supported by the published specifications for the Thermal Angel portable warming system, which is powered by a sealed lead-acid battery pack. This battery (which at 2.83 kg weighs >10 times more than the actual warmer) is rated at 1 kg of battery required per unit of blood or liter of fluid warmed.22 This limitation of the battery cannot be overcome by the clever design of the heat exchanger. Most Chemical Sources Are Impractical for Fluid Warming Another possible energy source involves direct liberation of energy contained within chemical compounds. One example of such a system deployed with every combat unit is the heater for meals ready to eat, which combines a small amount of water with an inorganic salt (usually iron) to generate an inorganic hydroxide or oxide and to yield large amounts of heat and liberal quantities of gas. Although the gas allows for convective heating of solid food, any heat carried by the gas is lost to a liquid unless the gas is bubbled through that liquid (which obviously is not practical for infused solutions). Many other compounds exist that liberate energy when combined with water, but all attempts to harness this heat for biological fluids have failed against practical thermodynamic considerations. The anhydrous inorganic salt with the highest energy density is aluminum chloride, which, when added to water, liberates 0.57 kcal/g (twice as much as sodium hydroxide and 4 times as much as lithium chloride). Therefore, to achieve the 350-kcal goal, again assuming reasonable heat transfer efficiency, >600 g of aluminum chloride is required (Fig. 9). It is not at all obvious how to harness this energy for transfer into blood, especially because the energy release is uncontrolled. Despite nearly 30 years of effort, such systems have not resulted in practical portable fluid warmers. FIGURE 9. View largeDownload slide Weight of energy that must be delivered to the casualty for thermal resuscitation, which is much lower for hydrocarbons than for other fuel sources. FIGURE 9. View largeDownload slide Weight of energy that must be delivered to the casualty for thermal resuscitation, which is much lower for hydrocarbons than for other fuel sources. Hydrocarbons Contain the Necessary Energy for Fluid Warming Hydrocarbons contain several orders of magnitude more energy per unit mass than do other energy sources. Butane, for example, liberates 11 kcal/g during combustion. Therefore, 350 kcal can be obtained from combustion of 32 g of butane. This reaction can be controlled by regulating the rate at which butane is supplied to the combustion site. Hydrocarbons have radically higher energy densities than the other available heat sources (Fig. 10). Therefore, a solution that relies on any other energy source necessarily must be wasteful of transport capacity. Also, any such system would be far less portable, because for a given system weight the available heat energy would be much less. FIGURE 10. View largeDownload slide Energy densities of batteries, aqueous heat-of-solution compounds (e.g., heaters for meals ready to eat), and hydrocarbons. could be used to power any of the existing warming technologies and methods mentioned previously. Why, then, is no hydrocarbon-based warming solution currently available? FIGURE 10. View largeDownload slide Energy densities of batteries, aqueous heat-of-solution compounds (e.g., heaters for meals ready to eat), and hydrocarbons. could be used to power any of the existing warming technologies and methods mentioned previously. Why, then, is no hydrocarbon-based warming solution currently available? What Barriers Exist for the Use of Hydrocarbons for Warming? It is important to note that a properly designed hydrocarbonfueled heat source, coupled to a suitable heat exchanger, The most obvious reason is that all deployed warming technologies originate from the civilian hospital setting, where electrical power is readily available. Also, the environmental conditions during transport and treatment in the civilian medical world do not favor the onset of hypothermia to the extreme degree seen in the forward echelons of combat casualty care. As stated previously, it is in these echelons with the least electricity-generating capability where rapid rewarming is most likely to have a beneficial clinical impact. Another barrier to the use of hydrocarbons for patient warming is the perceived danger from a combustible fuel source, particularly in the operating room or aircraft. The echelon 2 operating environment is typically heated via hydrocarbon (diesel fuel) combustion, and no flammable anesthetics are deployed. A combustion fuel source represents a potential ignition hazard during in-flight refueling, and this risk would need to mitigated if deployment aboard such aircraft is to be considered. SUMMARY Hypothermia is a major problem for combat casualties, and a practical solution does not currently exist. The most energy-efficient means of heat transfer into humans is direct transfer of heat into a central vein, and the morbidity of large-volume fluid administration requires this transfer to be performed through CAVR or continuous venovenous warming. Because of the large energy requirements to accomplish this task, the most logistically efficient energy choice for a portable system for hypothermia treatment is hydrocarbon combustion. Any hypothermia treatment that uses a method other than continuous central warming would be less effective clinically. Although energy choices other than hydrocarbons have been tried for warming, they do not contain enough energy for portable treatment of hypothermia in a practical fashion. Systems that rely on warming of intravenous fluids, although helpful in preventing hypothermia, cannot transmit enough energy to treat established hypothermia. The most favorable, active, thermal resuscitation solution, logistically, thermody-namically, and clinically, would use continuous central warming and a hydrocarbon-based fuel source. REFERENCES 1. Fujita H, Kawai M Temperature effect on isometric tension is mediated by regulatory proteins tropomyosin and troponin in bovine myocardium. J Physiol  2002; 539: 267– 76. Google Scholar CrossRef Search ADS PubMed  2. Chernow B, Lake R, Zaritsky A, et al.   Sympathetic nervous system “switch off” with severe hypothermia. Crit Care Med  1983; 11: 677. Google Scholar CrossRef Search ADS PubMed  3. Tokutomi T, Morioku K, Miyagi T, et al.   Optimal temperature for the management of severe traumatic brain injury: effect of hypothermia on intracranial pressure, system and intracranial hemodynamics, and metabolism. Neurosurgery  2003; 52: 102– 11. Google Scholar PubMed  4. Peng RY, Bongard FS Hypothermia in trauma patients. J Am Coll Surg  1999; 188: 685– 96. 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TI - Thermodynamic and Logistic Considerations for Treatment of Hypothermia
JF - Military Medicine
DO - 10.7205/MILMED.173.8.743
DA - 2008-08-01
UR - https://www.deepdyve.com/lp/oxford-university-press/thermodynamic-and-logistic-considerations-for-treatment-of-hypothermia-J21wq2KJfS
SP - 743
EP - 748
VL - 173
IS - 8
DP - DeepDyve
ER -