Human postburn oedema measured with the impression method

Bums (1993) 19, (6), 479-484

Printed in Great Britain

479

Human postburn oedema measured with the impression method 0. A. Lindahl’, J. Zdolsekz, F. Sjiiberg3 and K.-A. hgquist’ ‘Department of Biomedical Engineering, UmeH University Hospital and Linkbping University, ‘Department of Anaesthesiology and 3The Burns Unit, Department of Hand and Plastic Surgery, Linkijping University Hospital and aDepartment of Surgery, Umei University Hospital, Sweden

The course of tissue swelling in human non-injured skin affg bum injuy was inve.&igafedwith a non-invasive impression method that measures force and fissue fluid franslocafion during mechanical compression of the shin. Timedependenf changes in fhefluid franslocafion and fhe infersfifialpressure related to impression force were measured on I I occasions, during 3 weeks, in seven patients postbum. A mafhematical model was fittea’to the impression force curves and the parameters of the model depicted the time-dependent compartmental fluid shift in the postbum generalized oedema. Tissuefluid transhation increased significantly (P < 0. OS)up to a marimum value after 6 days posfbum and declined thereafter. This indicated a conffnuous increase in the generalized posfbum oeakma for the first 6 days posfbum. impression force at 3 weeks posfbum was significantly lower fP < O.OOl]as compared with the half-day posfbum value, indicating an imreased tissue pressure during the first days posfbum. Parameter analysis indicated aflux of wafer-like fluid from the vascukzfure to the infer&al space during the first 6 days posfbum. The spread of the values registered between different measurement sites was, however, large.

Introduction Imminent swelling or oedema of the injured skin is an apparent early clinical finding in burn victims. The understanding of these acute fluid shifts from the intravascular to the interstitial and intracellular compartments, causing the oedema, is incomplete (Lund et al., 1992). There have also been reports that if the burned skin area exceeds 25-30 per cent of total body surface area (TBSA), generalized oedema involving the non-injured skin and internal tissue appears (Arturson, 1979; Carvajal et al., 1979). This phenomena is especially pronounced when fluid replacement is given and the oedema fluid in these areas is relatively protein poor (Arturson and Jakobsson, 1985). However, distant effects have been observed on the mesenteric circulation with bum &juries as small as a few per cent of the body surface area Uelenko et al., 1973; Lund et al., 1992). Burn oedema occurs rapidly after injury, and continues to increase at a slower rate for several days (Baxter, 1974). Very few clinical studies on human subjects with postbum oedema have been reported (Lund et al., 1989). One reason is the lack of an accurate non-invasive instrument for continuous measurement of the oedema in the clinical situation. A new non-invasive method that measures oedema in s ecific tissue areas has recently been described (Mridha and 8 dman, 1986; Lindahl et al., 1991a). The method, called the 0 1993 Butterworth-Heinema 0305-4179/93/060479-06

Ltd

impression method, evaluates tissue oedema by measuring the resistive force of the tissue under compression. This force is suggested to be related to the mobility and volume of interstitial fluid translocated as a result of the compression. The method has been used to study the effect of pneumatic compression on human subjects with postmastectomy lymphoedema in the arm with promising results (Mridha and &man, 1989). Several parameters related to the oedema can be calculated from the force curve and these parameters have been evaluated in a rat testis model where the sensitivity of the parameters to volume change, pressure change and changes in interstitial fluid mobility have been examined (Lindahl et al., I991b). The aim of the present study was to investigate the course of tissue swelling in bum patients with the impression technique, during the first days postbum, in the non-injured skin sites. We calculated the fluid translocation parameter, analysed force curve parameters and studied how the different parameters changed from day to day after the bum injury.

Materials and methods Theory of the impression method

The principle of the impression method is based upon instantaneous impression of a circular impression head, with known diameter, to a predetermined depth into the tissue. The impression is then sustained for a preset time and the force required to do so is measured (Mridha and Odman, 1986). Initially, when an impression is done in tissue, the resistive force increases instantly to a maximum value and then declines during the measurement time to a minimum level (Figure la). The declining rate depends upon the fluid displacement in the tissue (Mridha and &Iman, 1986, 1989; Lindahl et al., 1991a,b). In this study a computerized instrument described by Lindahl et al. (1991a) was used to measure the force during mechanical impression of noninjured skin on postbum patients. The instrument was composed of an adjustable stand with a stepper motor that lowered an impression head toward the tissue. When the impression head touched the tissue and sensed a contact force of 50mN, the impression started and the impression head was lowered 4 mm into the tissue. The impression was sustained for 20s, during which resistive force was measured. The instrument used here had a maximal error in

Bums (1993) Vol. w/No. 6

480

and the fluid translocation parameter, FT [%], that estimates the displacement of interstitial fluid in the tissue caused by the impression. The FT parameter, earlier called integral (@IT) (Lindahl et al., 1991a,b) is calculated as T

4-

3-

FT= F

[[I - F,,(t)]dt J 0

where F,(t) = F(t)IF(O) is the normalized force and T is the registration time. The integration over the time T serves as a low-pass filter and reduces the influence of unwanted variations in the original force curve (Mridha and Odman, 1989). The FT parameter is schematically explained in Figure lb. The actual volume impressed by the circular impression head with area, A, during measurement on tissue is assumed to be the volume of a cylinder with area, A, and height, k, where k is the impression depth. Mridha and &lrnan (1986) used this as an assumption in the equation

I

i

V(t) = Ak(1 - F,(f)) = V(1 - F,(t))

(2)

where V(t) is the translocated fluid volume at time t, and V is the real impressed volume, Ah. The relation between FTand V(t) can be explained by combining equations (1) and (2): 7

I

I

(3) 0

Figure 1. Schematic diagrams showing: a, a typical force curve for a single T-second impression measurement. The impression force F(0) is the estimated peak force measured initially; b, normalized force curves for non-oedematous (small decay) and oedematous (large decay) tissue. The black area represents the FT value for the non-oedematous tissue and the black and grey area together the FT value for the oedematous tissue.

the force registration of less than 0.01 N (Lindahl et al., 1991a). Two parameters that are suggested to describe different properties of the oedema were calculated for each force curve: the impression force, F(O) (N), that describes the peak resistive force when tissue is instantly impressed (Figure Ia),

i.e. FTis the tissue fluid volume translocated during the time interval T, in proportion to the impressed volume, V. FT has a value between 0 and 100 per cent. Thus, a low value of FT indicates a low amount of displaceable interstitial fluid and a high value indicates the opposite. The computer programme of the impression apparatus gives a direct readout of FT, initial force, F(O), and the volume, V(f). Mathematical model for curve analysis As stated above, the impression measurement resulted in a decaying force curve (Figure I) due to the flow of fluid from the impressed site. This force curve was used for calculating the impression parameters. However, in order to get a more sophisticated analysis of the change of different fluids with different viscosities that compose the oedema at different times postbum, we fitted a parametric model to the

lower

5

0

b" Figure 2. a, Original impression force curves measured 8 h postburn, from a 15year-old injury. b, The corresponding normalized force curves.

1”

13

leg

upper

leg

lower

am

L”

time [s]

boy who suffered from a 35 per cent (TBSP.) burn

Lindahl et al.: Impression method for measuring postbum oedema

physically observed force curves. This was done in this study with a common parametric mathematical statistical model composed of a weighted sum of exponent& (van den Bos, 1982). The decay constants that describe the fluid flow are specific for a particular fluid or viscosity of fluid, while the weights are measures of fluid concentration (compare with radioactive decay measurement). In this study we assumed that the fluid in postbum oedema in non-injured skin is composed of two parts: one highviscosity gel-like fluid and one low-viscosity water-like fluid (Baxter, 1974; Lund et al., 1992). Consequently a model with a sum of two monoexponential terms (equation 4) characterizing low- and high-viscosity fluid flow was fitted to the observed normalized force curves. F(f) =A&

“‘1) + A,e’- “=z)

Mridha and Odman (1986) used a similar technique to fit a function with the sum of two monoexponential terms to the normalized force curves from non-oedematous skin and from lymphoedematous skin. They found that the constants in equation 4 were different for force curves from oedematous skin as compared with those from nonoedematous skin. Furthermore, after pneumatic compression treatment the constants for the force curves registered changed towards the constant values of non-oedematous skin. The first monoexponential term in equation 4 represents the flow of low-viscous water-like fluid and the second one represents the flow of gel-like higher viscosity fluid. Constants A, and A, represent the weight or fraction and T, and TZ the decay or time constants of low-viscosity and high-viscosity fluid, respectively. In this study we used a computerized simplex algorithm in Matlab (The Math Works, Inc., South Natick, MA, USA) to minimize the error function in the curve fit. The goodness of fit was estimated with a loss function (LF) calculated as the root-mean-square (RM.5) value of the difference between registered force curve and the fitted curve (equation 5): LF=

481

Impression measurements were done on four non-injured sites on the patient’s extremities at 0.5,1, 1.5,2,2.5,3,4,5,6 and 7 days postbum. Follow-up measurements, were also done at, or after, 3 weeks postbum. The measurement sites varied between patients dependent upon where the bum injury was located, and consequently where non-injured sites could be found. The usual measurement sites were hand, upper or lower arm, upper or lower leg or knee. The half-day measurement was used as the reference or contol value, since it was practically impossible to make a measurement immediately after burn injury. Consequently, since we know nothing about the F(0) and F7’values at the time before the half-day values, these parameters were only presented as the relative changes in time. The calculated F(0) and FT values have hence been considered as new observations that could be normalized. Statistics Values are expressed

as means f s.e.m. The ANOVA statistics were used combined with LSD (SAS Institute Inc., USA) for testing differences between groups. The Wilcoxon rank sum test was used for comparison between individual groups of normalized F(0) values. Correlation was expressed by the Pearson product-moment correlation. P< 0.05 was considered to be significant.

Results Force curves

Original force curves from the impression measurements, measured at the same time postbum but from different sites on the patients’ extremities, differed considerably as shown in the example in F&we 2~. Both the initial impression force, F(O), and the rate of decay differed. The corresponding normalized force curves (F(f)/F(O)) differed also, but to a lesser extent (Figure 2b). The mean curves of the normalized force curves differed in the rate of decay between different times after bum injury. Figure.3 shows an example in which the mean normalized force curve for day 6 postbum had a larger decay than the half-day postbum curve. However, the > 3 weeks postbum curve seems to approach the half-day curve.

where yf were the values of the fitted curve, y were the values from the real curve and n was the number of data-points. Impression

measurements

on postbwn

patients

Seven patients, with bum injuries, one female and six males, took part in this study. The patients were between 15 and 35 years of age and had burned skin areas covering between 10 and 47 per cent of total body surface area (TBSA). All patients were treated with initial crystalloid fluid therapy according to the Parkland formula (4 ml/kg/%). The impression apparatus was put on a trolley for easy transport and all measurements were performed at the bedside. The impression head was sterilized with 70 per cent alcohol before measurements were performed. The arm or leg of the patient was placed on the measurement table and the impression head was adjusted to be parallel to the skin under investigation, prior to measurement. Measurements were only carried out on non-injured skin sites. All force curves were saved on a floppy disc for further analysis. The contact force value was set to be 50 mN and the diameter of the impression head was 15 mm. Impression depth was set tobe4mm.

-~-half

day postburn

-->3

weeks postburn

-six 5

10

15

days postburn

20

time [s]

Figure 3. Normalized force curves (mean = solid line + s.e.m. = dotted line; N vanes between 20 and 26) for three different times postbum.

Bums (1993) Vol. 19/No. 6

482 Fluidtranslocation and impressive force Fluid translocation (FT) values that are supposed to be related to the interstitial fluid volume and impression force (F(0)) values that are suggested to be related to interstitial pressure were calculated for every single impression measurement. F&4re 4 shows an example of the time changes for single measurements of FT and F(O), where the FT values increased until day 6 and then declined as compared with the half-day value. The F (0) values started with a high value and then, after 3 days postburn, declined to a minimum value. For every measurement site on each patient, all fluid translocation (FT) values were normalized with the half-day postburn value, before means and s.e.m. were calculated for each time group. FT values increased significantly as compared with the half-day postburn values from day 2 until day 6 and declined thereafter towards the half-day values again (Figure 5). There was a significant increase in the FTvalues already after day 2, indicating a rapid formation of a generalized oedema. A plateau was found at day 3, but was not significant when compared with the values at day 6. The FT values at day 7 were significantly lower than the day 6

values, but there was no significant difference compared with the > 3-week values. The > 3-week values were not significantly different from the half-day values. The F(0) values were normalized with the half-day value in exactly the same way as with the FTvalues, before means and s.e.m. were calculated. There were no significant differences between the different time groups of F(0) values except for the > 3-week values (Figure 6). The > S-week values were significantly lower than the half-day values (PC 0.001).

Pigure4. Tiiedependent changes in fluid tramlocation (FIT) values and impression force (F(0)) values for single impression measurements on the right lower leg of a 35-year-old man with a 35 per cent (TBSA) bum injury.

Curve fittiig Figure3 shows examples of mean normalized force curves. Equation 4 was fitted to the mean curves of the individual time groups by means of a simplex algorithm that searches the minimum of the error function to the fit. A, and A, in M&Z describe the fraction of the total displaced low and high viscosity fluid, respectively. T, and T2 are the decay constant for the respective displacements and are inversely proportional to the fluid mobility. A,/(A, +A,) is the proportion of low-viscosity fluid (PropA,) and A,I(A, + A,) is the proportion of high-viscosity fluid (PropA,). TableI shows that there was a low proportion of low-viscosity fluid OrropA,) in the postburn oedema and that the mobility was very high (T,) as compared with the mobility of the high-viscosity fluid (T,). T, increased up to a maximum on day 3, while propA, was at its minimum on day 3. On day 6 the high-viscosity fluid had its lowest mobility value (T,) while T, was still high. Correlation analyses were performed for the different curve fitting parameters (Al, A,, T,, T,) versus the FTvalues. T, was negatively correlated to FT (r= - 0.86, P-C 0.0008, n = II), while T, was positively correlated (r= 0.61, PC 0.04, n = II). That is, the tissue-fluid mobility for the high-viscosity part, as determined by decay constant T,, increased as fluid translocation increased, while the tissuefluid mobility for the low-viscosity part of the fluid, as determined by decay constant T, decreased. A, had a low positive correlation to FT, but the correlation was not significant (r=O.M, PCO.59, TV=11). A,, on the other hand, had a non-significant negative correlation to FT (r= - 0.47, PCO.15, n= II).

E

E

0;+

>3weeks

time after burn [days]

L

0

2

4

6

>3weeks

time after burn [days]

Figure 5. Time-dependent changes in fluid tram&cation values (mean* s.e.m., N vanes between 24 and 31) afterbum injury. ‘PC 0.05 significantly different from the half-day FT value.

1

0

2

4

6

>3weeks

time after burn [days]

Figure 6. Tiiedependent changes in impression force values (mean& s.e.m., hJ vanes between 24 and 31) after burn injury. *P< 0.001 significantly smaller than the halfday F(0) value.

483

Lindahl et al.: Impression method for measuring postburn oedema

Table I. Curve-fitting data from mean normalized force curves (Ovaries between 21 and 31) at different times postbum. Loss function (LF)

varies between 0.003 and 0.009 Time postbum (days)

T*

T,

propA, m

P~OPA, (W

0.5 1 1.5 2 2.5 3 4 5 6 7

17 18 18 18 19 16 19 20 19 20

0.93 1.06 1.06 1.05 1.12 1.28 1.06 1.20 1.22 1.00

80 78 78 77 76 80 77 74 73 75

145 132 149 133 125 125 116 124 106 132

18 19 19 19 20 17 20 21 21 21

82 81 81 81 80 83 80 79 79 79

23 weeks

20

1.26

74

132

21

79

Discussion The present study shows that the impression method is suitable for following the course of tissue swelling in non-injured sites of postburn patients. It is also possible with this technique to investigate the fraction and mobility of the total displaced low- and high-viscosity fluids present in the generalized postburn oedema. We have previously shown that infusion of different volumes of rat plasma into rat testis tissue or hormone treatment of the rats gives significantly different FT values as measured with the impression method on rat testis. The measured impression force could detect changes in testicular interstitial volume as small as 16~1 (Lindahl et al., ‘1991b). Mridha and &man (1989) showed that it was possible to fit a mathematical model consisting of the sum of only two exponent& (equation 4) to the force curves and thereby differentiate between high- and low-viscosity fluid contribution to the force curve from lymph oedematous tissue. Furthermore, Mridha and &man (1986, 1989) analysed impression force curves from non-oedematous and pittingoedematous skin and concluded that impression force curves were best represented by the sum of two monoexponential terms. A third monoexponential term in the model gave only a very small or redundant contribution to the goodness of fit. We here further developed the suggested technique for generalized postburn oedema in order to understand better the fluid changes in the interstitial compartment over time. The curve fittings in this study were made on the mean normalized force curves for each measurement occasion (0.5, I, 1.5, 2, etc. days postburn) and not on each individual normalized force curve, which would have been preferable in order to ‘determine statistical significance between the parameters in the time groups. We tried to fit the individual curves but several curves had random disturbances due to movement, breathing or respirators which made the curvefitting procedure hazardous. We also tried to filter the individual curves with low pass digital filters (Butter-worth fifth order) but then we lost information about the time-0 force value where the frequency was high. Figure 7 shows an extremly distorted curve and the corresponding curve after filtering. Notice the change in time-0 value. Furthermore, the artefacts had both low- and high-frequency components (F&we 7a), which to our knowledge made it impossible to filter the individual curves appropriately without disturbing the information content. However, the artefacts did not affect the individual U-readings much. This is since the

integration over the time T (ec$ration 1) serves as a low pass filter and reduces the influence of small variations in the force curve (Mridha and &lman, 1989). The difficulty in the use of the curve-fitting procedure on extremely distorted force curves can probably be dealt with if only non-distorted curves are used for curve fitting or if routines for manual or computerized interpolations are developed. Further research must be performed to overcome these problems. Several authors have reported increases in protein extravasation, in tissue protein and in fluid content, giving a generalized oedema in patients postbum (for review see Lund et al., 1992). The significant increase in FT values, compared with the half-day FT value, in this study (Figure 2) gave further evidence in that direction. Moreover, the present study showed that the FT values increased until day 6, indicating an increase in the generalized oedema for 6 days postburn. We interpret that as a continuous extravasation of protein in the non-burned areas during the first 6 days postburn. Furthermore, T, (high-viscosity fluid decay constant) decreased until day 6, whereas the T, (lowviscosity fluid decay constant) was increased at day 6 as compared with the half-day value (Table I). This means that the mobility of the tissue fluid, as a whole, increased for the first 6 days postburn, probably as a result of a continuous 1,o

0,9

al 0,9 ,o

e

'0 0,7 ." ii

E E

l,o

I-

b

I

lW*

a

0,9 L

:;,[+ 1

0

b .

I

5

.

I

I

10

15

.

I

,

20

time [s] Figure 7. Example of a disturbed single normalized force curve before (a) and after (b) filtration with a 5th order Butterworth low pass filter.

484 addition of low-viscosity water-like fluid from the blood vessels to the interstitial space. The correlation analysis showed that T, increased significantly (r = 0.61), while T, decreased significantly (r= - 0.86), with increasing FT. Consequently, the increase in FT during the first 6 days postbum was linearly related to the change in mobility of the interstitial fluid. Summarizing, this indicates that the displaced interstitial fluid was continually becoming less viscous during the first 6 days postbum as a result of the continuing extravasation of protein. However, it is suggested that the generalized effect described above only occurs when the burned area exceeds 25-30 per cent TBSA (Arturson, 1961). Although the patient group in this study was small, seven patients, we tried to separate the FT values into two groups: one 10-25 per cent and one 30-47 per cent TBSA. The analysis of variance (ANOVA) for the divided groups showed no significant difference between the time-groups of FT values as compared with the half-day values. However, the F-test on the IO-25 per cent group (F = 0.98, P< 0.46) had lower significance than the F-test on the 30-47 per cent group (F= 1.82, PcO.06). As would be expected, these findings suggest that the generalized oedema was more pronounced in the group with the greater bum injury ( > 30 per cent). The curve-fitting data presented here @gableI) were different from curve fitting data reported earlier from impression measurements on patients with pitting postmastectomy lymphoedema (Mridha and &n-tan, 1989). The lymphoedematous patients had an almost equal fraction of (A, = 0.45 f 1.00) and high-viscosity low-viscosity (A,=O.Sl f 0.12) fluid, whereas the postbum patients in this study had a proportion of about 20 per cent lowviscosity fluid and 80 per cent high-viscosity fluid (Table I: 0.16
Burns (1993) Vol. 19/No. 6 In conclusion, the impression technique has been shown to be a relevant non-invasive tool to measure and evaluate postbum generalized oedema in human subjects. The course of tissue swelling in postbum non-injured skin could be easily followed at the bedside with minimal discomfort for the patient, and a mathematical model could be used to elucidate the change in fraction and mobility of interstitial fluid for different times postbum.

Acknowledgement This study was supported for Technical Development

by the National Swedish Board (grants 91-994, 92-6825).

References Arturson G. (1961) Pathophysiological aspects of the burn syndrome. Acfu Chir. Scmd. St&. 274, 1. Arturson G. (1979) Microvascular permeability to macromolecules in thermal injury. Acfu Physiol. Stand. Suppl. 463, 111. Arturson G. and Jakobsson 0. P. (1985) Measurements in a standard burn model. Bum 12, 1. Baxter C. R. (1974) Fluid volume and electrolyte changes of the early postburn period. Clin. Plmf. Surg. 4,693. Berardesca E., Gabba P., Farinelli N. et al. (1989) Skin extensibility time in women. Changes in relation to sex hormones. Acfu Dem. Venereal. (Sfockh.)69, 431. Carvajal H. F., Linares H. A. and Brouhard B. H. (1979) Relationship of burn size to vascular permeability changes in rats. Sttrg. Gynecol. Obsfef. 149, 193.

Escoffier C., de Rigal J., Rochefort A. et al. (1989) Age-related mechanical properties of human skin: an in vivo study. J. Invest. Demafol. 93,353.

Jelenko C., Jennings W. D., O’Kelley W. R. et al. (1973) Threshold burning effects on distant microcirculation. Arch. Swg. 106, 317. Lindahl O., Angquist K. A. and &man S. (1991a) Impression technique for the assessment of oedema. Med. Biol. Eng. Cornput. 29, 591. Lindahl O., Bergh A., Damber J.-E. et al. (I991b) Evaluation of the impression technique by measuring interstitial oedema in rat testis. Acfa Physiol. Scmd. 143, 255. Lund T., Bert J. L., Onarheim H. et al. (1989) Microvascular exchange during burn injury. I: a review. Circ. Shock 28, 179. Lund T., Onarheim H. and Reed R. K. (1992) Pathogenesis of edema formation in burn injuries. World J Surg. 16, 2. Mridha M. and &man S. (1986) Noninvasive method for the assessment of subcutaneous oedema. Med. Biol. Engl. Compuf. 24,393. Mridha M. and &lrnan, S. (1989) Fluid translocation measurement. Stand. ]. Rehab. Med. 21,63. van den Bos A. (1982) Parameter Estimation. In: Sydenham P. H. (ed.), Handbook of Measmmenf Science, ~011. Chichester: John Wiley, p. 332.

Paper accepted 6 May 1993

Correspondenceshould be addressed fo: Olof Lindahl, Department of Biomedical Engineering, University Hospital of Northern Sweden, S-901 85 UMEA, Sweden.