Exertional heat illness (EHI) spans a continuum of severity, ranging from relatively minor heat exhaustion, to heat injury, and more serious and potentially fatal exertional heat stroke (EHS). Heat exhaustion is characterized by hyperthermia and an inability to sustain cardiac output. Heat injury is a moderate to severe illness characterized by hyperthermia and indications of organ injury. The definitive feature of EHS is central nervous system dysfunction accompanied by hyperthermia, often but not always in excess of 40°C core body temperature. The severity and clinical outcome for an EHS casualty has a strong correlation with the area under the time and temperature curve for heat exposure (16). Although the Army has instituted preventive strategies and increased awareness of EHI, incidence rates have remained relatively unchanged in recent years. In 2014, the U.S. military reported 344 cases of heat stroke and more than 2000 cases of heat illness (1).
The consensus from a number of position statements and review articles is that the most effective method for rapidly cooling an EHS casualty is by cold water immersion (2,7,9,16,27,30,34). However, often in military training environments and in situations where cold water immersion is not feasible, “ice sheets” are used to treat EHIs as the preferred method for initial cooling. The U.S. Army Training and Doctrine Command (TRADOC) Regulation 350-29 established that “ice sheets” wrapped around the patient should be used as the first-line treatment of EHI upon its identification. “Ice sheets” are bed linens stored in a cooler filled with ice and water. Upon identification of a potential EHS casualty, the cold, wet bed linens are wrapped around the casualty to facilitate rapid cooling (35). Other methods of cooling, such as misting with cool water, fanning (with or without shade), tap water immersion, application of ice packs, and helicopter downdraft, result in slower cooling rates (9,31). Evidence suggests that rapid, immediate cooling to a body core temperature <38.9°C within 30 min results in the best clinical outcome (7), which reinforces the consensus that cold water immersion is the gold-standard of EHS treatment. There have been few case reports and no studies representing the utilization of cold intravenous (IV) saline treatment of EHI casualties in the prehospital setting.
In 2010, a panel of physicians, paramedics, and exercise physiologists met at Fort Benning, Georgia, to discuss treatment methods for soldiers potentially experiencing heat illness in an effort to reduce morbidity and mortality. Consequently, in 2011, Fort Benning implemented an updated prehospital protocol whereby IV cold (4°C) saline infusion was added to the preestablished TRADOC protocol of ice-sheeting. Additionally, a series of case reports from the Israeli Defense Force suggested that cold saline infusion may be an effective method of cooling an EHS casualty (16). The revised Fort Benning protocol directs that the cold saline infusion be initiated by Emergency Medical Services (EMS) during patient transport to the hospital. The present work examines whether the addition of IV cold saline to the prehospital management ice-sheeting protocol improves morbidity of EHI. The key markers of morbidity that were compared in this study are hospital length of stay (LOS) and degree of change of serum biomarkers.
While cold water immersion is the widely accepted criterion standard of treatment, this is not without contention; there have been some studies that suggest tepid water immersion has similar cooling rates as cold water immersion and other smaller studies that suggest equivalent efficacy of evaporative cooling with warm water (8). Cold gastric and peritoneal lavage is believed to be less efficacious due to required technical skill of the practitioner. The research indicates that regardless of application of the gold-standard cold water immersion therapy, early cooling and resuscitation minimize severe multiorgan dysfunction and death for patients with suspected heat illness (3,4,9,11,13,14,16–18,23,24,26,29,32,34,39). Indeed, case reports suggest that intravascular cooling and cold hemofiltration treatment benefits heat stroke patients experiencing multiorgan dysfunction (5,14,37). However, these case reports assessed patients who received this treatment in the hospital setting. The practice of intravascular cooling in treatment of suspected heat illness in a prehospital setting remains anecdotal. While there may be concerns over administering cold IV saline outside of the hospital setting, research has shown that noncontinuously infused cold (4°C) IV saline is unlikely to induce hypothermic core temperatures (22,25). It thus appears unlikely that administering cold IV saline outside of the hospital setting could be dangerous to patients.
Materials and Methods
This nonrandomized, retrospective cohort study assessed morbidity outcomes for heat casualties in two consecutive protocol groups. The first group received ice-sheeting protocol without cold IV saline while the latter group received ice-sheeting protocol that included cold IV saline infusion. Morbidity was assessed via duration of patients’ hospital stays and via serum biomarkers. A total of 314 heat casualties were admitted to Martin Army Community Hospital (MACH) at Fort Benning, between the years 2009 and 2012. These heat casualties were identified by the International Classification of Diseases (ICD-9) codes 992.0 through 992.9. This method of identifying heat casualties allowed for the spectrum of EHI ranging from minor heat exhaustion (admitted for observation) to severe heat stroke to be included in the study. This ensured that the study could account for any diagnosis within the heat illness spectrum that may have received an incorrect ICD-9 code.
Exclusion of heat casualties younger than 18 yr and older than 45 yr is to limit underlying disease and classic heat illness as a confounding variable. Because the population is exclusively active duty soldiers, who have received medical screenings and evaluations before enlistment or commissioning, the concern for medical conditions predisposing the heat injury was minimized, though not completely eliminated. Heat casualties admitted to MACH in the winter months (between November and March) also were excluded to account for underlying genetic predisposition to sensitivity to production of heat shock proteins and inflammatory cytokines (6). However, those with a history of previous heat illness were not excluded. In fact, two casualties had been admitted to MACH for repeat heat illness during the 4 yr observed in the study (Table 1).
Individuals were identified as potential heat illness casualties if they had been exposed to high environmental temperatures, if they had physically collapsed, and/or if they had altered mental status. For casualties in the TRADOC group, ice-sheeting was initiated by medics or cadre and EMS initiated ambient temperature IV normal saline infusion for resuscitation. The TRADOC Protocol was in accordance with TRADOC Regulation 350-29, which outlines the identification of suspected heat casualties and their prehospital management (35). Heat casualties in the Benning group also received a protocol treatment in accordance with TRADOC Regulation 350-29; however, rather than initiate ambient temperature saline, EMS initiated cold (4°C) IV saline infusion en route to the hospital.
In accordance with Martin Army Community Hospital's standard of care procedures, all heat casualties in the study received a standardized order set of labs trended every 6 to 8 h, beginning upon arrival to the emergency room (ER). This set of labs included a hemogram, a complete metabolic panel, initial cardiac enzymes, creatine phosphokinase (CPK), coagulation panel, lactate dehydrogenase, uric acid and urinalysis, including urine myoglobin. Outcome measures of interest included initial presenting creatinine (iCr), initial CPK (iCPK), aspartate aminotransferase (iAST), and alanine aminotransferase (iALT), trough creatinine (tCr), peak values of CPK (pCPK), aspartate aminotransferase (pAST), and alanine aminotransferase (pALT). Heat stroke has the complication risk of multiple organ failure including liver failure, disseminated intravascular coagulation (DIC), rhabdomyolysis, acute kidney injury (AKI), neurologic dysfunction, metabolic acidosis, circulatory collapses, and electrolyte abnormalities that may lead to dysrhythmias. Elevation in biomarkers of creatinine, CPK and transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) are associated with the development of these complications, increasing morbidity and potentially mortality (36,38).
Serum creatinine data was collected to monitor AKI. Serum CPK data were collected to monitor musculoskeletal damage or inflammation. Serum alanine aminotransferase and aspartate aminotransferase data were collected as markers for liver capsular inflammation, a surrogate marker used to measure liver failure secondary to accumulated heat stress. The other laboratory values within the standard order set trended for heat casualties were not collected for analyses because they are clinical indicators of complications rather than markers of heat illness morbidity.
Rates of change also were calculated as an additional variable for each of the collected data points and labeled as rCr, rCPK, rAST, and rALT. Dates of admittance and discharge were recorded and the LOS was calculated. LOS, used as an indirect marker of morbidity, was defined as the period from when a heat casualty's first laboratory was drawn until 12:00 p.m. the day of his or her documented discharge. Any data points with non-normal distributions were analyzed using the Mann-Whitney-Wilcoxon Ranked Sum Test using IBM SPSS Statistics software and STATA Data Analysis and Statistical software. This study was reviewed and approved by the Eisenhower Army Medical Center Human Use Review Committee. Because this study was retrospective and involved the analysis of preexisting medical records, informed consent was not required.
There were 290 EHI casualties during the study period, 153 (149 men, 4 women) in the TRADOC cohort and 137 (135 men, 2 women) in the Benning cohort (Table 2).
For the TRADOC group, LOS ranged from 1 to 9 d, and median LOS was 3 d. For the Benning group, LOS ranged from 1 to 7 d, and median LOS was 2 d (P < 0.0001 vs TRADOC).
The median iCr (also noted to be peak creatinine (Cr) or pCr) was 1.8 mg·dL−1 in TRADOC, which was significantly higher (P < 0.0001) than Benning group, where the median iCr was 1.4 mg·dL−1. The tCr also was significantly lower across groups: Benning had lower tCr levels than TRADOC group (difference of 0.1 mg·dL−1, P < 0.0001). However, no significant differences were found between groups' median rates of rCr change. A median rate of rCr change was 0.033 mg·dL−1·h−1 for TRADOC group and 0.032 mg·dL−1·h−1 for Benning group.
There were no significant differences in iCPK, pCPK, and rCPK between groups.
For TRADOC group, iAST ranged from 18 to 795 U·L−1, with a median iAST of 49 U·L−1. For Benning group, iAST ranged from 19 to 748 U·L−1, with a median iAST of 59 U·L−1. Median iAST was significantly higher (P < 0.05) in Benning group compared to TRADOC group. TRADOC group, pAST ranged from 25 to 6193 U·L−1, with a median pAST of 105 U·L−1. Benning group, pAST ranged from 20 to 1510 U·L−1, with a median pAST of 87 U·L−1. While no significant differences were found between groups' median pCPK levels (P > 0.05), Benning group had a significantly higher (P < 0.05) median rAST, declining more rapidly by 0.9 U·L−1·h−1 than the TRADOC group.
For TRADOC group, iALT ranged from 25 to 302 U·L−1, with a median iALT of 54 U·L−1. Benning group, iALT ranged from 6 to 318 U·L−1, with a median iALT of 36 U·L−1. Benning group had significantly lower (P < 0.0001) median iALT than TRADOC group. TRADOC group, pALT ranged from 34 to 6147 U·L−1, with a median pALT of 84 U·L−1. Benning group, pALT ranged from 9 to 922 U·L−1, with a median pALT of 106.3 U·L−1. Benning group had significantly higher (P < 0.05) median rALT, declining more rapidly by 0.33 U·L−1·h−1 TRADOC group.
This retrospective cohort study aimed to examine whether the morbidity of suspected EHI patients would improve by adding cold (4°C) IV saline infusion to the established prehospital management protocol of ice-sheeting. To examine this question empirically, we compared outcome measures for heat casualties who received an ice-sheeting protocol including cold IV saline infusion with casualties who received the same established ice-sheeting protocol that instead infused ambient temperature IV saline. Results demonstrated that heat casualties receiving the protocol that included cold IV saline infusion had significantly shorter hospitalization, lower peak creatinine values, and more rapidly declining rALT and rAST than casualties whose protocol included ambient IV saline infusions. These findings suggest that a protocol including cold (4°C) IV saline infusion would improve the morbidity of exertional heat injury or heat stroke casualties.
Length of hospital stay was used as a primary measure of overall morbidity. As the results demonstrated, the addition of cold IV saline to prehospital management protocol of ice-sheeting had a positive impact on morbidity as measured by 1 median hospital day. A potential confounder was the general discharge criteria of when AKI was resolved (defined as Cr lower than 1.3 mg·dL−1) and transaminases (ALT and AST) lower than three to five times the upper limit of normal, and a CPK lower than 10,000 U·L−1. Though a clear consensus of Cr lower than 1.3 mg·dL−1 was observed, there appeared to be some minor variations in CPK, ALT, and AST values at the time of discharge. These variations are believed to be due to the clinical preference of the attending physician, because there is no literature to date suggesting any particular value of CPK, ALT, or AST that is a safe “cutoff” for discharge. Data were collected from cases during the 2009 to 2012 timeframe, during which there was no known initiative as a hospital system to reduce LOS of admitted patients.
Acute kidney injury has a strong association with EHS. Factors related to AKI may include prerenal azotemia, heat storage, inflammation, and rhabdomyolysis (19,36,38). There are a number of factors that may have influenced the difference in initial (peak) creatinine between protocols. There may have been a greater duration of heat exposure and storage in the body of heat casualties in the TRADOC group compared with the Benning group. This would be assuming that an IV cold saline infusion lowers core body temperature faster than ambient temperature saline. Other confounding factors include incidences of rhabdomyolysis, environmental temperature and humidity at time of EHI, timeliness of identification of illness, and an individual's history of prior heat illness or time spent in the area to acclimatize. We are thus unable to account for all potential factors that may contribute to differences in initial (peak) creatinine across conditions. We also do not have baseline creatinine values for heat casualties. However, given our strict exclusion criteria, we assumed that all baseline creatinine values were normal. The hourly rate of return to baseline creatinine levels was equivalent in both groups, which is consistent with the primary treatment for AKI being aggressive fluid resuscitation. Lowest recovery creatinine values before discharge were clinically equivalent and thus, the data suggest that degree of kidney injury is the factor that most strongly relates to and influences duration of hospitalization. Moreover, these findings suggest that adding IV cold saline infusion before hospital admission for heat casualties likely reduces morbidity.
Serum CPK is a marker of muscular damage and inflammation that has been used to predict the severity of heat illness, the development of multiple organ dysfunction, and poor prognosis (36). Multiple case studies have found relations between elevated CPK and complications of rhabdomyolysis as well as with AKI; however, no consistent correlation has been found between a particular threshold level of serum CPK and either rhabdomyolysis complications or AKI (19,21,28,33). Excessive heat storage itself may be a cause for biomarker release as elevated CPK has been observed in the classic, non-EHIs. Though rhabdomyolysis may be a complication of heat illness, we chose not to collect data on its frequency of occurrence given that the nature of its treatment would not cause any clinical deviation from our protocols. The difference in ranges of pCPK could suggest a clinically significant difference in musculoskeletal inflammation between heat casualties receiving IV cold saline in addition to ice sheeting. However, this was not reflected in the median pCPK values between groups. It is possible that no significant differences were found across the groups' mean and median pCPK values because heat casualties included in the study only had mild to moderate severity heat illnesses. Given this possibility, we conducted a subsequent analysis to examine whether there exists a significant difference in mean and median pCPK values for heat casualties with more severe heat illness (defined as having serum biomarkers for creatinine greater than 1.2 mg·dL−1, CPK levels above 10,000 U·L−1, and ALT and AST values above five times the upper limit of normal). Results, however, demonstrated no significant differences between groups, possibly because only a subpopulation of heat casualties from each protocol group was included (i.e., those with more severe symptoms).
Transaminase elevations also have been used as indicators of heat illness prognosis and are hallmark features of heat stroke (36), thus it is difficult to diagnose heat stroke without using transaminase levels (12,15). However, there is no known correlating threshold between transaminase levels and encephalopathy or DIC, the two complications of heat illness directly related to death. In the present study, we observed no cases of DIC or liver failure that led to encephalopathy and death. ALT values indicated a statistically significant difference between groups, whereas serum AST values did not. The significant difference in ALT is unclear and may require further investigation; however, peak AST values were higher than peak ALT values, which is consistent with Sithinamsuwan et al. (32), Mil Med 2009, suggesting that AST may be a more sensitive marker of hepatic capsular inflammation or damage. A confounder to transaminase values may be the use of over-the-counter medications and supplements not accounted for in the medical documentation. These also may have led to elevated liver enzymes in heat casualties or may have predisposed an individual to heat injury. Protocol groups were not significantly different from one another regarding transaminase data. Moreover, no significant differences were found across groups even when analyses only included data from casualties with more severe heat illness.
Implications of our data include an overall cost savings due to shorter hospital stay for all, a more expeditious return to duty or return to training/play, and improved retention/fewer medical separations from military service. Data from a separate analysis of EHI at Ft. Benning indicated that a heat casualty admitted to MACH cost U.S. $5000 to U.S. $6800 per encounter (10). Reducing LOS by 33% (median LOS, 3 vs 2 d) has significant fiscal implications, when the annual numbers of EHI across the Department of Defense (DoD) are considered. Army Regulation 40–501 contains return to duty guidance for EHI casualties, based on injury severity and recovery time. Further research is needed to determine if the practice of cold IV saline infusion as part of prehospital treatment of EHI results in quicker return to duty and reduced rate of medical separation from military service.
The present study is not without limitations. Women were underrepresented in our sample (1.4% of our cases) but comprise approximately 15% of the total Army end-strength and suffer EHI at approximately 50% the rate in men (1,20). However, Ft. Benning is the location for initial entry training for recruits entering combat arms military occupational specialties, which until recently were restricted to men only. Although our sample may be representative of the population at risk at Ft. Benning, further research is necessary to confirm our findings in women. We did not collect ambient humidity and temperature data, which may have influenced the injury severity of heat casualties, nor did we collect body core temperature data. Although core temperature data were available for a limited number of EHI casualties, data regarding the time of measurement, in relation to when the individual collapsed, were either missing or highly variable. Therefore, our ability to calculate the impact of cold saline infusion on the core temperature cooling rate was severely limited. We cannot be certain that all prehospital responders (i.e., medics, cadre, EMS) adhered to these protocols. In-patient records did not document whether prehospital protocols were followed by responders, and researchers were unable to review hard-copy records of EMS/ER run sheets. Future studies should manipulate treatment type (i.e., cold IV saline or ambient temperature IV saline) to ensure that all participants receive the intended treatment.
The present study comparing different prehospital management protocols suggests that adding cold (4°) IV saline infusion to ice-sheeting in prehospital management of EHI casualties improves morbidity outcomes when the gold-standard cold water immersion therapy is not feasible. This is demonstrated by reduced hospital LOS, lower Cr values, and improved rates of ALT and AST decline. These findings suggest that the adjunct of cold IV saline in the prehospital management of EHI could benefit the military population, as well as individuals that may suffer from EHI in the civilian population, that is, occupational workers, marathon runners, football players, triathletes, etc. Given the increasing ready availability of cold (4°) IV saline for use in the Return of Spontaneous Circulation after Cardiopulmonary Resuscitation by EMS, its utilization is practical and cost effective. This study reinforces the implication of combining cooling techniques alternative to immersion therapy because field treatment may safely produce greater rates of cooling (31). However, a subsequent study comparing core temperature cooling rates between cold (4°) IV saline alone and in combination with ice-sheeting to that of cold water immersion therapy would be necessary to verify these implications.
The authors declare no conflict of interest and do not have any financial disclosures.
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