Report
Core temperature affects scalp skin temperature during scalp cooling Hein A. M. Daanen1,2, PhD, Mijke Peerbooms3, MSc, Corina J. G. van den Hurk3, PhD, Bernadet van Os2, MSc, Koen Levels1,2, MSc, Lennart P. J. Teunissen1,2, PhD, and Wim P. M. Breed3, MD, PhD
1 Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek (TNO [Dutch Organization for Applied Scientific Research]), Soesterberg, 2MOVE Research Institute, Faculty of Human Movement Sciences, VU University Amsterdam, The Netherlands, and 3Department of Research, Integraal Kankercentrum Zuid (Comprehensive Cancer Center South), Eindhoven, The Netherlands
Correspondence Hein A. M. Daanen, phd TNO, PO Box 23 3769 ZG Soesterberg The Netherlands E-mail: [email protected] Funding: This study was funded in part by Paxman Coolers Ltd, Huddersfield, UK. Conflicts of interest: None.
Abstract Background The efficacy of hair loss prevention by scalp cooling to prevent chemotherapy induced hair loss has been shown to be related to scalp skin temperature. Scalp skin temperature, however, is dependent not only on local cooling but also on the thermal status of the body. Objectives This study was conducted to investigate the effect of body temperature on scalp skin temperature. Methods We conducted experiments in which 13 healthy subjects consumed ice slurry to lower body temperature for 15 minutes after the start of scalp cooling and then performed two 12-minute cycle exercise sessions to increase body core temperature. Esophageal temperature (Tes), rectal temperature (Tre), mean skin temperature (eight locations, Tskin), and mean scalp temperature (five locations, Tscalp) were recorded. Results During the initial 10 minutes of scalp cooling, Tscalp decreased by >15 °C, whereas Tes decreased by 0.2 °C. After ice slurry ingestion, Tes, Tre, and Tskin were 35.8, 36.5, and 31.3 °C, respectively, and increased after exercise to 36.3, 37.3, and 33.0 °C, respectively. Tscalp was significantly correlated to Tes (r = 0.39, P < 0.01): an increase of 1 °C in Tes corresponded to an increase of 1.6 °C in Tscalp. Conclusions Slight cooling of patients with an elevated body temperature during scalp cooling contributes to the decrease in scalp temperature and may improve the prevention of hair loss. This may be useful if the desired decrease of scalp temperature cannot be obtained by scalp cooling systems.
Introduction
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Temporary chemotherapy-induced alopecia (CIA) is one of the most common and distressing side effects of chemotherapy treatment.1 It may lead to a negative body image, severe depression, and anxiety.2 Moreover, CIA constantly reminds the patient of the disease.3 Hair loss makes cancer visible to others in the environment, which is why some patients report the loss of hair as more troublesome than the loss of a breast.1 Despite this, the impact of CIA unfortunately remains inadequately recognized by many medical professionals.4 Scalp cooling techniques have been applied to prevent or at least reduce CIA since the 1970s. Currently, over twothirds of all Dutch hospitals offer scalp cooling to their patients, and the number is growing. Some medical professionals do not apply scalp cooling in some clinical situations. They are afraid that scalp cooling may protect tumor cells from the effect of chemotherapy if clinically International Journal of Dermatology 2015, 54, 916–921
unapparent metastases are present in the heavily vascularized scalp.5 However, to date this potential risk has been proven in only two patients with hematological malignancies, which are a contraindication for scalp cooling.6 About half of patients report that scalp skin cooling has satisfying results in terms of the prevention of hair loss.7 The type, dose, and infusion time of chemotherapy determine the result, but cooling parameters and patient characteristics also seem to be important.7,8 However, the optimal intensity and duration of cooling to prevent or reduce CIA are essentially unknown. Gregory et al.9 showed that the scalp temperature had to be less than 22 °C to prevent doxorubicin-induced alopecia. Cooling may reduce the metabolism of hair root cells in the scalp skin, which, in turn, possibly reduces the toxic effects of cytostatics on hair root cells.10 In addition, the hair-protecting mechanism of scalp cooling can be attributed to the reduction in the availability of cytostatics in hair root cells that occurs as a result of cold-induced vasoconstriction.11 ª 2015 The International Society of Dermatology
Daanen et al.
The vasoconstrictive state of the scalp skin depends not only on local skin temperature but also on body temperature. The mean body temperature is the weighted average of the relatively constant body core temperature (brain, heart) and the more variable peripheral tissue temperature, often assessed using mean skin temperature. A low body core temperature leads to increased sympathetic activity and thus to vasoconstriction in the skin. However, the possibility that a high body core temperature diminishes the effect of scalp cooling and thus may increase CIA cannot be excluded. A warm body tries to enhance heat loss, which is most successful if warm blood is diverted to cool areas, such as the scalp. Therefore, we investigated the effects of core temperature on scalp skin temperature during scalp cooling under well-controlled ambient conditions. We lowered the core temperature of our subjects by having them ingest ice slurry and thereafter increased their core temperature by means of exercise. We hypothesized that body core temperature proportionally affects scalp skin temperature and thus indirectly influences the effectiveness of scalp cooling.
Core temperature in chemotherapy-induced alopecia
Report
Figure 1 Schematic presentation of the timeline and measurement time-points (T1–T6)
equal to 1.5 times his body weight. Directly after each cycling session, measurements T4 (min 72) and T5 (min 89) were recorded. Finally, after a 5-minute period of rest, measurement T6 was recorded at 94 minutes. The experiment thus consisted
Materials and methods Subjects Thirteen healthy male subjects participated in this study. They had a mean standard deviation (SD) age of 33 17 years (range: 19–74 years), height of 182 8 cm (range: 168– 191 cm), and weight of 76 7 kg (range: 67–89 kg). Subjects were asked to follow their usual diets and perform their usual physical activities on the day immediately before the experiment and on the day of the experiment. Each subject was fully informed about the experiment and gave written consent. The experiment was approved by the institutional ethics committee and was conducted in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 1983. Protocol The experiment started with a 20-minute habituation period in a climatic chamber (Weiss Enet BV, Tiel, the Netherlands) set at 22 °C and 50% relative humidity, after which baseline measurements (T1) of rectal temperature (Tre), esophageal temperature (Tes), scalp skin temperature (Tscalp), and mean skin temperature (Tskin) were obtained (Fig. 1). At minute 25, scalp cooling was started (using a cap that was not pre-cooled), and measurement T2 was recorded at minute 35. The scalp cooling continued until the end of the experiment. At minute 40, subjects ingested syrup-flavored ice slurry (2 g/kg body weight in 5 min) to cool the body core. At minute 55, measurement T3 was performed and the exercise part of the experiment started. Each subject performed two cycle sessions of 12 minute each to increase body core temperature with a work load in Watt ª 2015 The International Society of Dermatology
of one session that included six phases during which temperatures were measured: Baseline; Scalp cooling; Ice slurry; Exercise 1; Exercise 2; and Rest.
Measurements The experiment started with the instrumentation of the subject. Subjects were dressed in a T-shirt, shorts, shoes, and socks. Esophageal (Tes) and rectal (Tre) temperatures were measured using thermistors (400 and 700 series, respectively; Yellow Springs Instruments, Inc., Yellow Springs, OH, USA). Thermistors were calibrated in a thermal water bath (Tamson TLC-15; Tamson Instruments BV, Bleiswijk, the Netherlands) before data acquisition using a certified Pt100 calibration thermometer (P650; Dostmann Electronic GmbH, Wertheim, Germany) with a resistance temperature sensor (PD-13/S; Tempcontrol Industrial Electronic Products BV, Voorburg, the Netherlands). The calibration instruments were accurate to 0.03 °C. Esophageal sensors were inserted through the nasal passage. The insertion depth beyond the nostrils was determined according to the formula: insertion depth (cm) = 0.479*sitting height (cm) 4.44,12 which ensured that the esophageal sensor was located at the level of thoracic vertebrae 8–9, close to the left ventricle. The rectal probe was inserted to a depth of 10 cm beyond the anal sphincter and fixed with tape to the lower back. The esophageal and rectal sensors were attached to a custom-made data acquisition system (VU University, Amsterdam, the Netherlands), consisting of a data logger with a medical power supply and LabVIEW software (National Instruments, Inc., Austin, TX, USA). Sample frequency was set at 1 Hz. Data on Tes were processed using a gating routine to remove negative peaks International Journal of Dermatology 2015, 54, 916–921
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Core temperature in chemotherapy-induced alopecia
exertion (RPE) was recorded at the end of the exercise phase (6 = not noticeable, 7 = extremely light, 9 = very light,
caused by the swallowing of relatively cool saliva. Skin temperature was determined using i-Buttons (DS1922L; Maxim Integrated Products, Inc., Sunnyvale, CA, USA) at eight
11 = light, 13 = a bit heavy, 15 = heavy, 17 = very heavy,
locations (forehead, right scapula, left upper chest, right arm in
19 = extremely heavy).
upper location, left arm in lower location, left hand, right anterior
Statistics Differences between measurements at different phases were evaluated using the GLM module in STATISTICA Version 8.0 (StatSoft, Inc., Tulsa, OK, USA). Dependent variables were Tes, Tre, Tskin, Tbody, Tscalp, Tforehead, and heart rate. Independent variables were subjects and measurement phase. Post hoc Fisher’s least significant differences (LSD) tests were performed when significant differences between the phases emerged. The relation between core temperature and scalp temperature was quantified calculating Pearson’s r for Tes and Tscalp. Phases 1 and 2 (up to ice slurry ingestion) were excluded because scalp temperature was not expected to be stable during these periods as the initial effects of local cooling persist for at least 20–30 minutes.9 Although Tes and Tre are both used to indicate body core temperature, their absolute values and time responses are quite different; therefore, both parameters were included in the analysis.
thigh, left calf), as described by ISO 9886. Mean skin temperature (Tskin) was calculated as the weighted average of readings at eight i-Buttons. Forehead skin temperature (Tforehead) was also analyzed separately because of its location close to the cooling area. A sample frequency of 0.1 Hz was used. Mean body temperature (Tbody) was calculated using the following general equation: Tbody = a*Tes + (1 a)*Tskin, where a was set at 0.7. Scalp skin temperature was measured using copper– constantan thermocouples at five locations on the scalp. The unweighted average of the readings of the five thermocouples represented the mean scalp skin temperature (Tscalp). Scalp cooling was performed with a Paxman PSC-1 cooling machine (Paxman Coolers Ltd, Huddersfield, UK). The cooling machine was switched on at least 30 minutes prior to the experiment to achieve a coolant temperature between
6 °C. Before
5 and
scalp cooling started, the cooling cap of the optimal size was selected to obtain the best possible fit to the subject’s scalp. Gauze swabs were used to avoid direct skin contact with the cap when the subject was (partly) bald or when ears were in contact with the cooling cap.
Results Gagging reflexes prevented the insertion of the esophageal probe in one subject, and esophageal data were unreliable in one subject. Thus esophageal temperature data from 11 subjects were available for analysis. Table 1 shows the rectal, esophageal, mean skin, forehead, mean scalp skin, and mean body temperatures in all subjects in every phase of the experiment. Heart rate,
Heart rate was measured during the entire experiment using a Polar sport tester (Polar Electro Oy, Kempele, Finland) at 5-second intervals. Subjects rated thermal sensation (TS) on a 9-point scale ( 4 = very cold,
3 = cold,
2 = cool,
1 = slightly cool,
0 = neutral, 1 = slightly warm, 2 = warm, 3 = hot, 4 = very hot) at every measurement time-point.13 The rate of perceived
Table 1 Mean standard deviation (SD) esophageal temperature (Tes), rectal temperature (Tre), mean skin temperature (Tskin),
mean body temperature (Tbody), scalp temperature (Tscalp), forehead temperature (Tforehead), heart rate, thermal sensation (TS) and rate of perceived exertion (RPE) in all subjects during every phase of the experiment Time-point
Variable Tes, °C Tre, °C Tskin, °C Tbody, °C Tscalp, °C Tforehead, °C Heart rate, bpm TS, au RPE, au
1 Mean SD 36.5 37.0 32.3 35.2 32.1 33.9 64.9 0.1
0.2 0.2 0.4 0.2 0.5 0.4 8.2 0.5
2 Mean SD 36.3 36.9 31.8 35.0 17.0 31.1 65.2 1.3
0.2 0.2 0.6 0.2 1.3 2.1 8.2 0.9
3 Mean SD 35.8 36.5 31.3 34.5 13.5 28.5 62.7 1.8
0.3 0.3 0.5 0.2 1.7 3.2 10.6 1.1
4 Mean SD 36.2 36.8 31.8 34.8 14.0 28.1 75.7 0.8 12
0.3 0.3 0.5 0.2 1.8 3.0 13.2 0.9 1
5 Mean SD 36.3 37.3 33.0 35.3 14.9 29.9 73.4 1.9 14
0.5 0.3 0.6 0.3 1.9 3.6 19.7 1.6 2
6 Mean SD 36.5 37.3 32.3 35.3 14.6 28.8 71.4 0.3
0.3 0.3 0.5 0.2 1.2 3.1 15.7 1.0
Values in bold differ significantly from those obtained in the first phase. bpm, beats per min; au, arbitrary units. International Journal of Dermatology 2015, 54, 916–921
ª 2015 The International Society of Dermatology
Daanen et al.
TS, and RPE are also shown. Data are reported as the mean SD. Differences between subjects were highly significant. Differences between phases were observed for Tes (F5,50 = 17.5, P < 0.001), Tre (F5,60 = 57.2, P < 0.001), Tskin (F5,60 = 39.8, P < 0.001), Tbody (F5,60 = 61.7, P < 0.001), Tscalp (F5,59 = 771.2, P < 0.001), Tforehead (F5,60 = 26.9, P < 0.001), and heart rate (F5,60 = 3.9, P < 0.001). After 10 minutes of scalp cooling (measurement T2), significant drops in core and skin temperatures were observed, and scalp temperature decreased by >15 °C. Tes and Tre dropped by 0.2 and 0.1 °C, respectively. The drop in mean body temperature of 0.27 °C in 10 minutes equals a net heat loss of 119 W. Hereafter, body cooling continued according to the combined effects of ice slurry ingestion and scalp cooling. In 20 minutes, Tbody dropped 0.50 °C below the baseline temperature, representing a net heat loss of 111 W. Tscalp dropped by 3.5 °C from period T2 to period T3. Scalp skin temperature did not differ among T4, T5, and T6. Forehead temperature did not differ among T3, T4, T5, and T6. The heat generated by exercise (T4 and T5) increased Tbody to values slightly above those obtained at baseline. Thermal sensation decreased for T2 and T3 and was higher for T4 and T5. Ratings for RPE increased from 12 (between light and a bit heavy) to 14 (between a bit heavy and heavy) in the second period. The relationship between Tes and Tscalp is shown in Figure 2. The relationship between Tbody and Tscalp is shown in Figure 3. The correlation between Tes and Tscalp is 0.39 (P = 0.01), and the correlation between Tbody and Tscalp is 0.37 (P < 0.05). For each increase of 1 °C in Tes, Tscalp increased by 1.6 °C, and for each increase of 1 °C in Tbody, Tscalp increased by 1.9 °C. Discussion The aim of this study was to investigate the effects of body temperature on scalp skin temperature during scalp cooling. The temperature of the scalp skin shows a relationship with esophageal temperature and mean body temperature. Figures 2 and 3 show that, despite considerable variation, lower core and mean body temperatures are reflected in a lower scalp skin temperature. Therefore, we can accept the hypothesis that core temperature is related to scalp skin temperature. In this study, core temperature was assessed using Tes and Tre. In general, Tre is about 0.2 °C higher than Tes during rest.14 However, our results show much larger differences for two reasons: ice slurry cooled the esophageal tissue, and exercise increased peripheral blood flow so ª 2015 The International Society of Dermatology
Core temperature in chemotherapy-induced alopecia
Report
Figure 2 Relationship between esophageal temperature and scalp temperature in 11 subjects at four phases (phases 1 and 2 are excluded). The correlation coefficient is 0.39
Figure 3 Relationship between mean body temperature and scalp temperature in 11 subjects at four phases (phases 1 and 2 are excluded). The correlation coefficient is 0.37
that cold blood was mixed with warm blood in the circulation. The esophageal probe was located close to the right atrium of the heart and therefore was sensitive to blood temperature changes.15 At the end of exercise, the difference between Tre and Tes was about 1 °C (Table 1). Esophageal temperature is generally considered a much better indicator of core temperature than rectal temperature because the latter has a considerable time delay. Core temperature was manipulated using ice slurry ingestion and exercise. Other methods of manipulating core temperature include passive heating and cooling using a water-perfused suit or exposure to cold air. However, these methods are uncomfortable and time-consuming. The use of pyrogens to increase body core temperature is another option. Pyrogens, however, affect not only body temperature but also the immune system, International Journal of Dermatology 2015, 54, 916–921
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and we tried to avoid such effects. In fever, the core temperature thermostat in the hypothalamus is set at a higher level, and heat loss mechanisms are reduced to maintain this threshold, whereas in exercise heat loss is enhanced to restore the temperature to the original level.16 Data from phases 1 and 2 were excluded from the analysis of the relationship between Tes and Tscalp because scalp temperature was still stabilizing during this period. Measurement T3, however, occurred 30 minutes after the initiation of scalp cooling, a moment at which scalp skin temperatures can be expected to be stable.17 If we assume that scalp skin temperature is related to the efficacy of scalp cooling in line with the observations of Gregory et al.,9 we are led to recommend that body core temperature should not be increased during scalp cooling. Obviously, the most important measure is to further cool the scalp skin, but this can be experienced as unpleasant, particularly during the initial 15 minutes, although only about 3% of patients stop the treatment as a result of discomfort.18 Furthermore, it is questionable whether more profound cooling leads to further decreases in skin blood flow and biochemical activity in hair root cells. For instance, Bulow et al.10 observed no further decrease in scalp perfusion when scalp temperature dropped to
Core temperature affects scalp skin temperature during scalp cooling Hein A. M. Daanen1,2, PhD, Mijke Peerbooms3, MSc, Corina J. G. van den Hurk3, PhD, Bernadet van Os2, MSc, Koen Levels1,2, MSc, Lennart P. J. Teunissen1,2, PhD, and Wim P. M. Breed3, MD, PhD
1 Nederlandse Organisatie voor Toegepast Natuurwetenschappelijk Onderzoek (TNO [Dutch Organization for Applied Scientific Research]), Soesterberg, 2MOVE Research Institute, Faculty of Human Movement Sciences, VU University Amsterdam, The Netherlands, and 3Department of Research, Integraal Kankercentrum Zuid (Comprehensive Cancer Center South), Eindhoven, The Netherlands
Correspondence Hein A. M. Daanen, phd TNO, PO Box 23 3769 ZG Soesterberg The Netherlands E-mail: [email protected] Funding: This study was funded in part by Paxman Coolers Ltd, Huddersfield, UK. Conflicts of interest: None.
Abstract Background The efficacy of hair loss prevention by scalp cooling to prevent chemotherapy induced hair loss has been shown to be related to scalp skin temperature. Scalp skin temperature, however, is dependent not only on local cooling but also on the thermal status of the body. Objectives This study was conducted to investigate the effect of body temperature on scalp skin temperature. Methods We conducted experiments in which 13 healthy subjects consumed ice slurry to lower body temperature for 15 minutes after the start of scalp cooling and then performed two 12-minute cycle exercise sessions to increase body core temperature. Esophageal temperature (Tes), rectal temperature (Tre), mean skin temperature (eight locations, Tskin), and mean scalp temperature (five locations, Tscalp) were recorded. Results During the initial 10 minutes of scalp cooling, Tscalp decreased by >15 °C, whereas Tes decreased by 0.2 °C. After ice slurry ingestion, Tes, Tre, and Tskin were 35.8, 36.5, and 31.3 °C, respectively, and increased after exercise to 36.3, 37.3, and 33.0 °C, respectively. Tscalp was significantly correlated to Tes (r = 0.39, P < 0.01): an increase of 1 °C in Tes corresponded to an increase of 1.6 °C in Tscalp. Conclusions Slight cooling of patients with an elevated body temperature during scalp cooling contributes to the decrease in scalp temperature and may improve the prevention of hair loss. This may be useful if the desired decrease of scalp temperature cannot be obtained by scalp cooling systems.
Introduction
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Temporary chemotherapy-induced alopecia (CIA) is one of the most common and distressing side effects of chemotherapy treatment.1 It may lead to a negative body image, severe depression, and anxiety.2 Moreover, CIA constantly reminds the patient of the disease.3 Hair loss makes cancer visible to others in the environment, which is why some patients report the loss of hair as more troublesome than the loss of a breast.1 Despite this, the impact of CIA unfortunately remains inadequately recognized by many medical professionals.4 Scalp cooling techniques have been applied to prevent or at least reduce CIA since the 1970s. Currently, over twothirds of all Dutch hospitals offer scalp cooling to their patients, and the number is growing. Some medical professionals do not apply scalp cooling in some clinical situations. They are afraid that scalp cooling may protect tumor cells from the effect of chemotherapy if clinically International Journal of Dermatology 2015, 54, 916–921
unapparent metastases are present in the heavily vascularized scalp.5 However, to date this potential risk has been proven in only two patients with hematological malignancies, which are a contraindication for scalp cooling.6 About half of patients report that scalp skin cooling has satisfying results in terms of the prevention of hair loss.7 The type, dose, and infusion time of chemotherapy determine the result, but cooling parameters and patient characteristics also seem to be important.7,8 However, the optimal intensity and duration of cooling to prevent or reduce CIA are essentially unknown. Gregory et al.9 showed that the scalp temperature had to be less than 22 °C to prevent doxorubicin-induced alopecia. Cooling may reduce the metabolism of hair root cells in the scalp skin, which, in turn, possibly reduces the toxic effects of cytostatics on hair root cells.10 In addition, the hair-protecting mechanism of scalp cooling can be attributed to the reduction in the availability of cytostatics in hair root cells that occurs as a result of cold-induced vasoconstriction.11 ª 2015 The International Society of Dermatology
Daanen et al.
The vasoconstrictive state of the scalp skin depends not only on local skin temperature but also on body temperature. The mean body temperature is the weighted average of the relatively constant body core temperature (brain, heart) and the more variable peripheral tissue temperature, often assessed using mean skin temperature. A low body core temperature leads to increased sympathetic activity and thus to vasoconstriction in the skin. However, the possibility that a high body core temperature diminishes the effect of scalp cooling and thus may increase CIA cannot be excluded. A warm body tries to enhance heat loss, which is most successful if warm blood is diverted to cool areas, such as the scalp. Therefore, we investigated the effects of core temperature on scalp skin temperature during scalp cooling under well-controlled ambient conditions. We lowered the core temperature of our subjects by having them ingest ice slurry and thereafter increased their core temperature by means of exercise. We hypothesized that body core temperature proportionally affects scalp skin temperature and thus indirectly influences the effectiveness of scalp cooling.
Core temperature in chemotherapy-induced alopecia
Report
Figure 1 Schematic presentation of the timeline and measurement time-points (T1–T6)
equal to 1.5 times his body weight. Directly after each cycling session, measurements T4 (min 72) and T5 (min 89) were recorded. Finally, after a 5-minute period of rest, measurement T6 was recorded at 94 minutes. The experiment thus consisted
Materials and methods Subjects Thirteen healthy male subjects participated in this study. They had a mean standard deviation (SD) age of 33 17 years (range: 19–74 years), height of 182 8 cm (range: 168– 191 cm), and weight of 76 7 kg (range: 67–89 kg). Subjects were asked to follow their usual diets and perform their usual physical activities on the day immediately before the experiment and on the day of the experiment. Each subject was fully informed about the experiment and gave written consent. The experiment was approved by the institutional ethics committee and was conducted in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 1983. Protocol The experiment started with a 20-minute habituation period in a climatic chamber (Weiss Enet BV, Tiel, the Netherlands) set at 22 °C and 50% relative humidity, after which baseline measurements (T1) of rectal temperature (Tre), esophageal temperature (Tes), scalp skin temperature (Tscalp), and mean skin temperature (Tskin) were obtained (Fig. 1). At minute 25, scalp cooling was started (using a cap that was not pre-cooled), and measurement T2 was recorded at minute 35. The scalp cooling continued until the end of the experiment. At minute 40, subjects ingested syrup-flavored ice slurry (2 g/kg body weight in 5 min) to cool the body core. At minute 55, measurement T3 was performed and the exercise part of the experiment started. Each subject performed two cycle sessions of 12 minute each to increase body core temperature with a work load in Watt ª 2015 The International Society of Dermatology
of one session that included six phases during which temperatures were measured: Baseline; Scalp cooling; Ice slurry; Exercise 1; Exercise 2; and Rest.
Measurements The experiment started with the instrumentation of the subject. Subjects were dressed in a T-shirt, shorts, shoes, and socks. Esophageal (Tes) and rectal (Tre) temperatures were measured using thermistors (400 and 700 series, respectively; Yellow Springs Instruments, Inc., Yellow Springs, OH, USA). Thermistors were calibrated in a thermal water bath (Tamson TLC-15; Tamson Instruments BV, Bleiswijk, the Netherlands) before data acquisition using a certified Pt100 calibration thermometer (P650; Dostmann Electronic GmbH, Wertheim, Germany) with a resistance temperature sensor (PD-13/S; Tempcontrol Industrial Electronic Products BV, Voorburg, the Netherlands). The calibration instruments were accurate to 0.03 °C. Esophageal sensors were inserted through the nasal passage. The insertion depth beyond the nostrils was determined according to the formula: insertion depth (cm) = 0.479*sitting height (cm) 4.44,12 which ensured that the esophageal sensor was located at the level of thoracic vertebrae 8–9, close to the left ventricle. The rectal probe was inserted to a depth of 10 cm beyond the anal sphincter and fixed with tape to the lower back. The esophageal and rectal sensors were attached to a custom-made data acquisition system (VU University, Amsterdam, the Netherlands), consisting of a data logger with a medical power supply and LabVIEW software (National Instruments, Inc., Austin, TX, USA). Sample frequency was set at 1 Hz. Data on Tes were processed using a gating routine to remove negative peaks International Journal of Dermatology 2015, 54, 916–921
917
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Core temperature in chemotherapy-induced alopecia
exertion (RPE) was recorded at the end of the exercise phase (6 = not noticeable, 7 = extremely light, 9 = very light,
caused by the swallowing of relatively cool saliva. Skin temperature was determined using i-Buttons (DS1922L; Maxim Integrated Products, Inc., Sunnyvale, CA, USA) at eight
11 = light, 13 = a bit heavy, 15 = heavy, 17 = very heavy,
locations (forehead, right scapula, left upper chest, right arm in
19 = extremely heavy).
upper location, left arm in lower location, left hand, right anterior
Statistics Differences between measurements at different phases were evaluated using the GLM module in STATISTICA Version 8.0 (StatSoft, Inc., Tulsa, OK, USA). Dependent variables were Tes, Tre, Tskin, Tbody, Tscalp, Tforehead, and heart rate. Independent variables were subjects and measurement phase. Post hoc Fisher’s least significant differences (LSD) tests were performed when significant differences between the phases emerged. The relation between core temperature and scalp temperature was quantified calculating Pearson’s r for Tes and Tscalp. Phases 1 and 2 (up to ice slurry ingestion) were excluded because scalp temperature was not expected to be stable during these periods as the initial effects of local cooling persist for at least 20–30 minutes.9 Although Tes and Tre are both used to indicate body core temperature, their absolute values and time responses are quite different; therefore, both parameters were included in the analysis.
thigh, left calf), as described by ISO 9886. Mean skin temperature (Tskin) was calculated as the weighted average of readings at eight i-Buttons. Forehead skin temperature (Tforehead) was also analyzed separately because of its location close to the cooling area. A sample frequency of 0.1 Hz was used. Mean body temperature (Tbody) was calculated using the following general equation: Tbody = a*Tes + (1 a)*Tskin, where a was set at 0.7. Scalp skin temperature was measured using copper– constantan thermocouples at five locations on the scalp. The unweighted average of the readings of the five thermocouples represented the mean scalp skin temperature (Tscalp). Scalp cooling was performed with a Paxman PSC-1 cooling machine (Paxman Coolers Ltd, Huddersfield, UK). The cooling machine was switched on at least 30 minutes prior to the experiment to achieve a coolant temperature between
6 °C. Before
5 and
scalp cooling started, the cooling cap of the optimal size was selected to obtain the best possible fit to the subject’s scalp. Gauze swabs were used to avoid direct skin contact with the cap when the subject was (partly) bald or when ears were in contact with the cooling cap.
Results Gagging reflexes prevented the insertion of the esophageal probe in one subject, and esophageal data were unreliable in one subject. Thus esophageal temperature data from 11 subjects were available for analysis. Table 1 shows the rectal, esophageal, mean skin, forehead, mean scalp skin, and mean body temperatures in all subjects in every phase of the experiment. Heart rate,
Heart rate was measured during the entire experiment using a Polar sport tester (Polar Electro Oy, Kempele, Finland) at 5-second intervals. Subjects rated thermal sensation (TS) on a 9-point scale ( 4 = very cold,
3 = cold,
2 = cool,
1 = slightly cool,
0 = neutral, 1 = slightly warm, 2 = warm, 3 = hot, 4 = very hot) at every measurement time-point.13 The rate of perceived
Table 1 Mean standard deviation (SD) esophageal temperature (Tes), rectal temperature (Tre), mean skin temperature (Tskin),
mean body temperature (Tbody), scalp temperature (Tscalp), forehead temperature (Tforehead), heart rate, thermal sensation (TS) and rate of perceived exertion (RPE) in all subjects during every phase of the experiment Time-point
Variable Tes, °C Tre, °C Tskin, °C Tbody, °C Tscalp, °C Tforehead, °C Heart rate, bpm TS, au RPE, au
1 Mean SD 36.5 37.0 32.3 35.2 32.1 33.9 64.9 0.1
0.2 0.2 0.4 0.2 0.5 0.4 8.2 0.5
2 Mean SD 36.3 36.9 31.8 35.0 17.0 31.1 65.2 1.3
0.2 0.2 0.6 0.2 1.3 2.1 8.2 0.9
3 Mean SD 35.8 36.5 31.3 34.5 13.5 28.5 62.7 1.8
0.3 0.3 0.5 0.2 1.7 3.2 10.6 1.1
4 Mean SD 36.2 36.8 31.8 34.8 14.0 28.1 75.7 0.8 12
0.3 0.3 0.5 0.2 1.8 3.0 13.2 0.9 1
5 Mean SD 36.3 37.3 33.0 35.3 14.9 29.9 73.4 1.9 14
0.5 0.3 0.6 0.3 1.9 3.6 19.7 1.6 2
6 Mean SD 36.5 37.3 32.3 35.3 14.6 28.8 71.4 0.3
0.3 0.3 0.5 0.2 1.2 3.1 15.7 1.0
Values in bold differ significantly from those obtained in the first phase. bpm, beats per min; au, arbitrary units. International Journal of Dermatology 2015, 54, 916–921
ª 2015 The International Society of Dermatology
Daanen et al.
TS, and RPE are also shown. Data are reported as the mean SD. Differences between subjects were highly significant. Differences between phases were observed for Tes (F5,50 = 17.5, P < 0.001), Tre (F5,60 = 57.2, P < 0.001), Tskin (F5,60 = 39.8, P < 0.001), Tbody (F5,60 = 61.7, P < 0.001), Tscalp (F5,59 = 771.2, P < 0.001), Tforehead (F5,60 = 26.9, P < 0.001), and heart rate (F5,60 = 3.9, P < 0.001). After 10 minutes of scalp cooling (measurement T2), significant drops in core and skin temperatures were observed, and scalp temperature decreased by >15 °C. Tes and Tre dropped by 0.2 and 0.1 °C, respectively. The drop in mean body temperature of 0.27 °C in 10 minutes equals a net heat loss of 119 W. Hereafter, body cooling continued according to the combined effects of ice slurry ingestion and scalp cooling. In 20 minutes, Tbody dropped 0.50 °C below the baseline temperature, representing a net heat loss of 111 W. Tscalp dropped by 3.5 °C from period T2 to period T3. Scalp skin temperature did not differ among T4, T5, and T6. Forehead temperature did not differ among T3, T4, T5, and T6. The heat generated by exercise (T4 and T5) increased Tbody to values slightly above those obtained at baseline. Thermal sensation decreased for T2 and T3 and was higher for T4 and T5. Ratings for RPE increased from 12 (between light and a bit heavy) to 14 (between a bit heavy and heavy) in the second period. The relationship between Tes and Tscalp is shown in Figure 2. The relationship between Tbody and Tscalp is shown in Figure 3. The correlation between Tes and Tscalp is 0.39 (P = 0.01), and the correlation between Tbody and Tscalp is 0.37 (P < 0.05). For each increase of 1 °C in Tes, Tscalp increased by 1.6 °C, and for each increase of 1 °C in Tbody, Tscalp increased by 1.9 °C. Discussion The aim of this study was to investigate the effects of body temperature on scalp skin temperature during scalp cooling. The temperature of the scalp skin shows a relationship with esophageal temperature and mean body temperature. Figures 2 and 3 show that, despite considerable variation, lower core and mean body temperatures are reflected in a lower scalp skin temperature. Therefore, we can accept the hypothesis that core temperature is related to scalp skin temperature. In this study, core temperature was assessed using Tes and Tre. In general, Tre is about 0.2 °C higher than Tes during rest.14 However, our results show much larger differences for two reasons: ice slurry cooled the esophageal tissue, and exercise increased peripheral blood flow so ª 2015 The International Society of Dermatology
Core temperature in chemotherapy-induced alopecia
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Figure 2 Relationship between esophageal temperature and scalp temperature in 11 subjects at four phases (phases 1 and 2 are excluded). The correlation coefficient is 0.39
Figure 3 Relationship between mean body temperature and scalp temperature in 11 subjects at four phases (phases 1 and 2 are excluded). The correlation coefficient is 0.37
that cold blood was mixed with warm blood in the circulation. The esophageal probe was located close to the right atrium of the heart and therefore was sensitive to blood temperature changes.15 At the end of exercise, the difference between Tre and Tes was about 1 °C (Table 1). Esophageal temperature is generally considered a much better indicator of core temperature than rectal temperature because the latter has a considerable time delay. Core temperature was manipulated using ice slurry ingestion and exercise. Other methods of manipulating core temperature include passive heating and cooling using a water-perfused suit or exposure to cold air. However, these methods are uncomfortable and time-consuming. The use of pyrogens to increase body core temperature is another option. Pyrogens, however, affect not only body temperature but also the immune system, International Journal of Dermatology 2015, 54, 916–921
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Core temperature in chemotherapy-induced alopecia
and we tried to avoid such effects. In fever, the core temperature thermostat in the hypothalamus is set at a higher level, and heat loss mechanisms are reduced to maintain this threshold, whereas in exercise heat loss is enhanced to restore the temperature to the original level.16 Data from phases 1 and 2 were excluded from the analysis of the relationship between Tes and Tscalp because scalp temperature was still stabilizing during this period. Measurement T3, however, occurred 30 minutes after the initiation of scalp cooling, a moment at which scalp skin temperatures can be expected to be stable.17 If we assume that scalp skin temperature is related to the efficacy of scalp cooling in line with the observations of Gregory et al.,9 we are led to recommend that body core temperature should not be increased during scalp cooling. Obviously, the most important measure is to further cool the scalp skin, but this can be experienced as unpleasant, particularly during the initial 15 minutes, although only about 3% of patients stop the treatment as a result of discomfort.18 Furthermore, it is questionable whether more profound cooling leads to further decreases in skin blood flow and biochemical activity in hair root cells. For instance, Bulow et al.10 observed no further decrease in scalp perfusion when scalp temperature dropped to
