The Role of an Ingestible Telemetric Thermometer in Preventing Exertional Heat Stroke, for a Patient with Healed Massive Burns Running the 2007 London Marathon

JBUR-3302; No. of Pages 7

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Case report The role of an ingestible telemetric thermometer in preventing exertional heat stroke, for a patient with healed massive burns running the 2007 London marathon

Ryckie G. Wade a, Peter Dziewulski b, Bruce M. Philp b,* a University of East Anglia, Norwich, United Kingdom b St. Andrew’s Centre, Broomﬁeld Hospital, Chelmsford, United Kingdom

article info external fixator. He required multiple surgical procedures to heal his burn wounds including free flap reconstruction of his Article history: forehead, and later free flap nasal reconstruction. He was Accepted 12 May 2010 discharged from hospital after 150 days. As a previous Ironman triathlete, the patient was deter- mined to return to competitive sports and began training for the London marathon 2007, 12 months after his initial injuries. 1. Introduction He was fitted with an Otto Bock Hydraulic Knee and O˝ ssur Flex-Foot to run. In addition, he used a lightweight below- Adequate thermoregulation relies upon an intact dermis and elbow prosthesis with a body powered split-hook terminal epidermis [1,2]. Cutaneous vessels dilate to dissipate heat device. However, the inability to sweat in burn injured and (‘‘dry heat loss’’ via conduction, convection and radiation) and grafted areas meant that he required a method of monitoring constrict in order to retain heat. Dermal sweat glands are vital his core temperature whilst exercising, in order to take adnexal structures required for heat loss during exercise via appropriate action to avoid hyperthermia. To monitor core evaporation (‘‘wet heat loss’’). It is generally believed that temperature, the CorTempTM ingestible telemetric sensor by extensive thermal damage to the integumentary system HQ Inc. was purchased at a cost of £1314.76 (Fig. 1). impairs thermoregulation for a variety of reasons. In 2007, the patient completed the London marathon in 7 h and 14 min (Fig. 2). The ingestible telemetric thermometer was ingested 4 h prior to exercise to ensure adequate readings 2. Case history thereafter and to remove interference from intake of foods or liquids. The device took serial recordings of his core In April 2004, a 38-year-old civil engineer injured in a road temperature (8C) and time elapsed. A PolarTM S625 sports Â traffic accident, sustained 75% full thickness flame burns to watch was used to record heart rate (beats/min; bpm). A his face, scalp, left chest and back, and circumference burns of GarminTM ForerunnerTM personal GPS device was used to his left arm and both legs. His injuries were complicated by record speed. This data was transmitted to and recorded on an smoke inhalation and a fracture of the left femoral shaft. external device which he carried. He was also able to tag and The patient underwent immediate total burn excision, categorise the data by pace as either ‘‘Run’’, ‘‘Walk’’ or ‘‘Rest’’ trans-radial/ulnar amputation of the left forearm and a left and usually employed the order or running, then walking and disarticulation knee amputation and full body escharotomy then resting if his core temperature did not normalise whilst and fasciotomy. The left femoral fracture was treated with an walking. The data presented in Tables 1 and 2 were analysed

* Corresponding author at: Department of Plastic reconstructive and Burns Surgery, St. Andrew’s Centre, Broomﬁeld Hospital, CM1 7ET Chelmsford, United Kingdom. Tel.: +44 1245 516122. E-mail addresses: [email protected] (R.G. Wade), [email protected] (P. Dziewulski), [email protected] (B.M. Philp). 0305-4179/$36.00 # 2010 Published by Elsevier Ltd and ISBI. doi:10.1016/j.burns.2010.05.012

Please cite this article in press as: Wade RG, et al. The role of an ingestible telemetric thermometer in preventing exertional heat stroke, for a patient with healed massive burns running the 2007 London marathon. Burns (2010), doi:10.1016/j.burns.2010.05.012 JBUR-3302; No. of Pages 7

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with SPSS v17.0 (Chicago, IL) for means, standard deviations (SD), Pearson’s correlation coefficients and compared with two-tailed paired-samples t-tests. One-way ANOVA was performed with Bonferroni correction to compare resting, walking and running core temperature and average heart rate. Significance was set at the 5% level. The patient’s start core temperature (at 0 min) was 37.39 8C. His mean core temperature for the marathon was 39.18 8C (+1.79 8C); mean running core temperature was 39.26 8C (+1.87 8C) and walking was 39.16 8C (+1.77 8C). The patient took six rest periods when his core temperature reached 39.5 8C – this allowed him to cool by a mean of 0.39 8C over a mean of 11 min and 7 s, per rest. The patient completed the marathon with a core temperature of 39.70 8C (+2.31 8C from baseline), which took over 3 h to return to baseline. There was a statistically significant positive correlation between marathon time elapsed and core temperature (r = 0.295, p = 0.049). As he ran, there was a positive correlation between time and core temperature (r = 0.288, p = 0.233). When the patient slowed to a walk, there was a negative correlation between core temperature and time (r = 0.023, À p = 0.929). Furthermore, when the patient stopped to rest, there was a negative correlation between core temperature and time (r = 0.273, p = 0.29). À During the marathon, the patient’s mean HR was 163 bpm (SD = 13). His mean heart rate when running was 172 bpm, when walking was 162 bpm and when resting was 144 bpm. Interestingly, there was a negative correlation between marathon time elapsed and average heart rate (r = 0.170, À p = 0.265), which became statistically significant when we controlled for ‘‘running’’ (r = 0.675, p = 0.001) and ‘‘walking’’ À (r = 0.588, p = 0.13) paces. However, as expected there was a À positive correlation between heart rate and time spent ‘‘resting’’ (r = 0.464, p = 0.354). There was no statistically significant difference between core temperature when resting and walking ( p = 0.301), resting and running ( p = 0.242) or walking and running ( p = 0.239) with paired t-tests. ANOVA demonstrated no significant difference between the pace (walking, running or resting) and core temperature ( p = 0.329) or heart rate ( p = 0.210).

3. Discussion

Previous studies have shown that persons with healed massive burns (>40% TBSA) have a reduced ability to dissipate heat, especially during exercise [3,4]. Although other areas of normal skin may sweat excessively, heat is produced faster than it can be dispelled and core temperature rises [3–7]. Skin temperature is inversely proportional to core temperate tolerance, however, little is known about the alterations in the thermoregulatory physiology of persons with healed massive burns. During a marathon, skin temperature is directly related to Fig. 1 – The CorTempTM ingestible telemetric thermometer external conditions including ambient temperature, humidity as compared to a standard mercury thermometer (top), the and air motion [8,9]. Conversely, core temperature is essen- external recording device with example pills in relative tially independent of environmental conditions [10] and size (middle) and a cross section of the pill showing the mostly dependent on metabolic rate [11]. Metabolic rate is inner components (bottom). proportional to the amount of energy expended and the speciﬁc heat of 1 kg of healthy body tissue which approx-

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Fig. 2 – The patient crossing the finishing line with his teammate, of the London Team Triathlon 2007.

imates to 3.5 kJ/8C/kg. During a typical marathon, heat subconsciously regulate their pace according to afferent production in a healthy adult rises exponentially and without feedback from tissues and the environment, in order to dissipation, core temperature would reach fatal levels within optimise muscle/skin blood flow, normalise their core 5 km/10 min [12]. It is unknown whether such physiological temperature and enhance performance [21]. We therefore parameters are mirrored in patients with healed burns or how hypothesise that patients with impaired thermoregualtion metabolic rate varies. Our patient usually ran for 5–10 min who wish to exercise maximally may safely do so in an inverse before having to stop/slow, which suggests that his ability to manner, by continuously monitoring their core temperature dissipate heat was significantly impaired. Further research and thereafter, consciously regulating their pace to avoid into exercise capacity is needed and how capacity relates to hyperthermia. TBSA. Marathon runners with healthy skin architecture com- Sweating is the most efficient means of heat loss (by monly finish a race with core temperatures of 38.5–39.5 8C, but evaporation) and largely unaffected by other physiological can have (rectal) core temperatures in excess of 40 8C [15,22– parameters. Vasodilatation is the inadequate alternative (by 24]. Recent trials on Ironman Triatheles found that (rectal) core convection), although maintenance of a blood pressure is a temperatures increased by only 1 8C from baseline [25] as quintessential prerequisite [13,14] and thus, vasodilatation is compared to novice athletes whose core temperatures only possible in well hydrated individuals, with normal skin frequently exceeded 40 8C [24]. Duffield et al. [19] reported architecture. Most marathons are not held in extreme weather that core temperature (as measured by ingestible telemetric conditions, however, air temperature can change by up to thermometry) in Australian footballers was linearly related to 17 8C from the start to finish of a race [15]; this unpredictability the intensity and duration of exercise (thus metabolic rate); makes race preparation difficult and exposes runners to the most players’ core temperature increased to a maximum of risk of dehydration and collapse. Without an adequate means 39.5 8C, at which time players automatically slowed their of heat loss, as in our patient, core temperature rises and falls running pace to reduce their core temperature. However, such in synchrony with metabolic rate and so to ensure optimal data cannot be safely extrapolated to patients with impaired thermoregulation during a marathon, runners should be heat thermoregualtion. Comparison studies of children with 40– acclimatised and well hydrated [16]. 70% healed burns and healthy controls have shown compara- Ambient temperature and humidity can predict marathon ble (tympanic) core temperature after 20 min of submaximal runner’s finishing times [17]. Although core temperature is exercise [26] and cardiopulmonary stress testing [27]. Austin independent of outside temperatures, skin temperature (and et al. [3] who showed that core temperature did not rise so blood flow) is not. Blood is diverted from respiring muscles significantly in adults with TBSA < 40%, whom exercised for to the skin in warm weather to facilitate heat loss and so, can 1 h in ambient climates. The studies by McIntyre, MlCak and reduce runner’s performance. Metabolic rate is known to be Austin on burns patients are in conflict with our findings directly proportional to core temperature [18] and so, the which may be because rectal temperatures were measured too importance of pacing strategies (dictating metabolic rate) in quickly and exercise was not intense enough. The students of regulating core temperature and so avoiding hyperthermia is Duffield, Laursen and Pugh suggest that core temperature rises widely reported [19,20]. It is assumed therefore, that runners in proportion to the intensity and duration of exercise.

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Table 1 – The raw data recorded by the HQ Inc CorTempTM Ingestible Telemetric Thermometer. Time corrected (h:min:s) Pace Average heart rate (BPM) Core temperature (8C)

00:00:00 START 119 37.39 00:10:14 Run 168 Off 00:12:16 Walk 158 Off 00:22:16 Run 176 Off 00:25:17 Walk 161 Off 00:36:34 Run 177 Off 00:39:11 Walk 166 39.18 00:40:10 ? 161 39.20 00:50:23 Run 177 39.34 00:56:53 Walk 162 39.12 01:06:58 Run 176 39.13 01:09:01 Walk 168 39.12 01:18:38 Run 176 39.27 01:20:55 Walk 167 39.25 01:25:55 Rest 141 38.66 01:39:09 Run 169 38.76 01:41:12 Walk 164 38.76 01:51:17 Run 175 38.86 01:53:48 Walk 164 38.96 02:03:51 Run 175 39.09 02:08:05 Walk 166 39.13 02:18:08 Run 176 39.25 02:21:39 Walk 168 39.30 02:31:42 Run 175 39.38 02:36:08 Walk 168 39.43 02:45:44 Run 177 39.49 02:55:24 Walk 167 39.55 03:05:34 Run 179 39.72 03:10:28 Walk 168 39.77 03:37:01 Rest 134 38.59 04:36:49 Walk 150 38.32 04:47:30 Run 172 38.79 04:50:00 Walk 163 38.90 04:58:30 Run 176 39.30 05:14:52 REST 145 38.83 05:25:00 Run 168 39.10 05:27:29 Walk 164 39.20 05:37:40 Run 173 39.61 05:46:58 Rest 155 39.66 05:54:54 Walk 138 39.16 06:05:05 Run 164 39.27 06:12:38 Walk 151 39.25 06:21:59 Run 164 39.18 06:27:04 Rest 139 39.10 06:39:43 Run 163 39.29 06:42:47 Walk 157 39.32 06:53:02 Run 165 39.32 06:57:10 Rest 149 39.26 06:58:14 Run 150 39.25 07:14:38 FINISH 168 39.70 07:19:38 Rest – 39.72 07:24:38 Rest – 39.61 07:29:38 Rest – 39.52 07:34:38 Rest – 39.40 07:39:38 Rest – 39.23 07:44:38 Rest – 39.06 07:54:38 Rest – 38.73 08:04:38 Rest – 38.41 08:14:38 Rest – 38.36 09:14:38 Rest – 37.59 10:14:38 Rest – 37.45

The time was recorded from ingestion just prior to the marathon commencement, to excretion of the device (in hours, minutes and seconds). Time elapsed was stamped and categorised by the patient’s pace of ‘‘Run’’, ‘‘Walk’’ and ‘‘Rest’’. The heart rate was recorded in beats per minute (BPM) and a minute-by-minute average recorded for each pace. The core temperature was recorded constantly and presented as an average of each pace. The bolded text signiﬁes the completion of the marathon (7 h, 14 min and 38 s).

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Table 2 – The mean (SD), minimum and maximum core temperatures (8C) and average heart rate (beats/min, bpm) throughout the marathon. Core temperature (8C) Heart rate (bpm) Mean (SD) Min Max Mean (SD) Min Max

Before 37.39 – – 119 – – Run 39.3 (0.27) 38.8 39.7 163.7 (11.4) 138 177 Walk 39.2 (0.32) 38.3 39.8 169.3 (8.28) 145 179 Rest 39.0 (0.41) 38.6 39.7 159.8 (14.4) 134 176 Finish 39.7 – – 168 – –

However, there are clearly mechanisms which limit tempera- metabolism, electrolyte derangement and plasma membrane ture rise and alter thermotolerance in both healthy persons lysis. Further sequaelae include; cardiogenic shock due to and those with TBSA < 40% which has yet to be fully ventricular hypokinesia; acute renal failure due to rhabdomy- elucidated. To date there are no published data on exercise olysis and thermal induced tubular suppression; gut wall stress testing in patients with healed massive burns. oedema leading to endotoxic shock and DIC secondary to The relationship between exercise performance and core widespread thrombin release. The best treatment is prompt temperature tolerance is incompletely understood [28] but cooling in an ice bath with a target core temperature of 36 8C likely to have a multifaceted aetiology, involving cellular [37], which may be achieved in 20–30 min [38]. To date, rectal and systemic changes [16].Studiesonthemostthermo- thermometry is the only proven method of measuring core sensitive intracellular heat shock protein (iHsp72) have temperature in these athletes [37]. There are no published demonstrated its release in response to rising temperature guidelines on EHS avoidance in high-risk individuals, such as and its role in releasing numerous inflammatory cytokines, those with healed massive burns. facilitating the repair and impedance of heat damaged cells, Rectal [39,40] and oesophageal [41,42] temperature mea- and end-organ changes aimed at reducing core temperature surements are reproducible, reliable, not biased by environ- [29,30]. iHsp72 has therefore become a marker for thermo- mental temperatures and reflect core temperature. However, tolerance, whereby lower levels imply higher tolerance and rectal temperature is slow to reveal changes to core visa versa. It has been shown that persons subject to daily temperature [43–46], is inaccurate during cold/windy weather hyperthermia (39 8C) and vigorous exercise (60 min of 80% [47] and neither of the methods is ideal for monitoring core maximal exercise, for 1 week) have reduced iHsp72 expres- temperature during sporting activities or for rapid patient sion and therefore, have lower core temperatures and are assessment, when EHS is suspected. Tympanic thermometry better and longer able to tolerate higher core temperatures is perhaps the best known and most commonly employed [31]. This in vitro hypothesis was proven in vivo when method of measuring core temperature, although this tool is Fehrenbach et al. [32] reported reduced expression of iHsp72 unreliable in marathon runners (due to environmental bias) in half marathoners. The same group later showed that in and has poor agreement with rectal thermometry in similar marathon runners, expression of iHsp72 is directly propor- circumstances [48]. Many studies have demonstrated the tional to the duration and intensity of exercise (i.e., benefits of ingestible telemetric thermometry during activi- exhaustive exercise is a more potent inducer) [33].These ties which are unsuitable for intermittent rectal/oesopha- findings fit with the general consensus that by controlling geal/tympanic thermometry and require continuous core pace, core temperature can be sustained within the normal temperature assessment [46,49–55].Thesestudiessuggest range. However, there is no research to date examining the that for continuously monitoring athletes core temperature, expression of heat shock proteins in patients with healed ingestible telemetric thermometry is the most practical and massive burns or their relation to pace and metabolic rate. accurate means. The evidence suggests that healthy adults gain tolerance to Ingestible telemetric temperature sensors were invented in high temperatures through training/acclimatisation for at the 1960s although only recently gained widespread use. The least 60 min/day, for at least 1 week [32,34,35] or 2 weeks for particular device employed in this case was the CorTempTM marathons [36]. We speculate that burns patients gain Ingestible Telemetric Thermometer (HQ Inc, FL, USA) as tolerance to higher core temperatures and reduce their set shown in Fig. 1. The system consists of an ingestible ‘‘pill’’ point by modulating the expression of such HSPs and from thermometer and external sensor. The ‘‘pill’’, measuring 2 cm other as yet unclear mechanisms, at rest and during in length, may be swallowed prior to exercise/activity and exercise. Therefore, adults with healed burns may safely measures the temperature of the gut wall as it travels through and maximally exercise provided that they undertake the gastrointestinal tract. It constantly sends wireless real- thorough preparation remain sufficiently hydrated and time readings to the short-range external device (e.g., wrist monitor their core temperature to guide their running pace. watch) to inform the user of their vital signs. A meta-analysis Exertional heat stroke (EHS) is a well recognised and by Byrne and Lim [56] showed a 95% agreement with <0.1 8C potentially fatal medical emergency. Defined as a core bias when compared to oesophageal and rectal thermometry temperature >40 8C with CNS dysfunction or other sign(s) of in healthy subjects. This proved the efficacy of intestinal organ dysfunction due to hypercytokineaemia; EHS can telemetric temperature measurement, but also highlighted rapidly result in irreversible tissue injury due to accelerated optimal ingestion times and the need for careful calibration

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