Research Papers

Level of Cutaneous Blood Flow Depression During Cryotherapy Depends on Applied Temperature: Criteria for Protocol Design

[+] Author and Article Information
Sepideh Khoshnevis

Department of Biomedical Engineering,
The University of Texas at Austin,
107 W. Dean Keeton Street, Stop C0800,
Austin, TX 78712
e-mail: sepideh@utexas.edu

R. Matthew Brothers

Department of Kinesiology,
University of Texas at Arlington,
MAC 114,
Arlington, TX 78229
e-mail: matthew.brothers@uta.edu

Kenneth R. Diller

Fellow ASME
Department of Biomedical Engineering,
The University of Texas at Austin,
107 W. Dean Keeton Street, Stop C0800,
Austin, TX 78712
e-mail: kdiller@mail.utexas.edu

1Corresponding author.

Manuscript received April 24, 2018; final manuscript received September 6, 2018; published online October 1, 2018. Assoc. Editor: Stavroula Balabani.

ASME J of Medical Diagnostics 1(4), 041007 (Oct 01, 2018) (9 pages) Paper No: JESMDT-18-1020; doi: 10.1115/1.4041463 History: Received April 24, 2018; Revised September 06, 2018

Cryotherapy is commonly used for the management of soft tissue injury. The dose effect of the applied cooling temperature has not been quantified previously. Six subjects were exposed during five different experiments to local skin temperatures of 16.6 °C, 19.8 °C, 24.7 °C, 27.3 °C, and 37.2 °C for 1 h of active heat transfer followed by 2 h of passive environmental interaction. Skin blood perfusion and temperature were measured continuously at treatment and control sites. All treatments resulted in significant changes in cutaneous vascular conductance (CVC, skin perfusion/mean arterial pressure) compared to baseline values. The drop in CVC for cooling to both 19.8 °C and 16.6 °C was significantly larger than for 27.3 °C (P < 0.05 and P < 0.0005, respectively). The depression of CVC for cooling to 16.6 °C was significantly larger than at 24.7 °C (P < 0.05). Active warming at 37.2 °C produced more than a twofold increase in CVC (P < 0.05). A simulation model was developed to describe the coupled effects of exposure time and temperature on skin perfusion. The model was applied to define an equivalent cooling dose defined by exposure time and temperature that produced equivalent changes in skin perfusion. The model was verified with data from 22 independent cryotherapy experiments. The equivalent doses were applied to develop a nomogram to identify therapeutic time and temperature combinations that would produce a targeted vascular response. The nomogram may be applied to design cryotherapy protocols that will yield a desired vascular response history that may combine the benefits of tissue temperature reduction while diminishing the risk of collateral ischemic injury.

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Grahic Jump Location
Fig. 1

Final CVC values as a function of skin temperature manipulation during cooling and warming trials. Significantly different CVC pairs are marked (**, ***, and #). CVC shows a significant decrease or increase in all temperature protocols with respect to the baseline values (* and #). Error bars indicate the standard deviations in CVC and temperature. (n = 6).

Grahic Jump Location
Fig. 2

Cutaneous vascular conductance as percent of its average baseline value. Data points and solid lines represent the measured and fitted data, respectively. Data are averaged across the six subjects. The solid lines show the extrapolation of CVC for four hours beyond the termination of active cooling or warming. (a) cooling experiments and (b) warming experiment.

Grahic Jump Location
Fig. 3

Cutaneous vascular conductance deficit for cooling experiments calculated based on the AUC on the extrapolated fitted data. The blue data plot shows CVC gain for warming experiment with its y-axis to the right. CVC deficit and gain plots from cooling and warming experiments provide an easier approach to comparing deficit and gain in CVC with different cooling and warming temperatures. The black labels on the cooling plots mark the perfusion deficit at 30, 45, and 60 min for the 16.6 °C data and the corresponding equivalent perfusion deficits for all other cooling experiments. The marks on warming plot show the times required to completely cancel the CVC deficit accrued from cooling.

Grahic Jump Location
Fig. 4

Thermal therapy protocol design nomogram. For a reference cooling temperature (16.6 °C) and an arbitrary duration (50 min in this example), a (hyphenated) line connecting 16.6 °C on the cooling temperature axis and 50 min on the 16.6 °C cooling duration axis intersects the 37.2 °C warming at 32 min, which is the time required to offset the CVC deficit accrued during cooling. A (dashed) line from a time on the 16.6 °C cooling duration axis drawn to intersect a different temperature on the cooling temperature axis (19.8 °C in this example) will intersect the cooling duration axis at the time required to produce an equivalent depression of CVC (59 min in this example). The dotted lines mark a region of uncertainty for calculating the equivalent cooling dose as derived using Eq. (5) based on the standard error and mean calculated for the three S values presented in Table 3. Other combinations of cooling temperature and cooling and warming duration can be determined with alternate assumptions.

Grahic Jump Location
Fig. 5

Cutaneous vascular conductance histories during passive rewarming: (a) measured data for each cooling temperature trial and (b) data offset for direct comparison by shifting the 19.8 °C, 27.3 °C, and 24.7 °C curves downward using Eq. (4) to remove the offset compared to the 16.6 °C trial



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