Objectives: In this study, we re-evaluated the relationship between pit recovery time (PRT) and serum albumin levels and elucidated the factors influencing PRT.

Design: Cross-sectional study.

Setting: Patients who visited the outpatient department or were admitted to a small urban hospital in Japan.

Participants: 135 adult Japanese patients with bilateral lower extremity pitting oedema.

Interventions:

Primary and secondary outcome measures: This study assessed the correlation between PRT and serum albumin levels, calculated the predictive accuracy for identifying a group with low albumin levels when the PRT of the lower leg was < 40 s, and identified variables that influence PRT.

Results: We found no significant correlation between lower leg PRT and serum albumin levels. Furthermore, a PRT of < 40 s was largely ineffective in predicting low albumin levels. Factors influencing PRT included the diagnosis of malnutrition oedema, examinations conducted during hospitalisation, diagnosis of cardiac oedema, use of diuretics, thickness of the lower limb soft tissue, serum creatinine level, estimated right ventricular systolic pressure (RVSP), age, serum albumin level, potassium level, and blood urea nitrogen to serum creatinine ratio. Notable correlations with PRT were observed in relation to lower limb soft tissue thickness, age, and estimated RVSP.

Conclusions: Given that the PRT is influenced by multiple factors, its correlation with serum albumin levels is weak. Thus, predicting hypoalbuminaemia based solely on PRT is inaccurate.

Study design: This was a cross-sectional study in a single hospital.

Study population: This study included patients aged 15 years or older (to exclude children) who visited the outpatient department or were admitted to the Department of Internal Medicine at the Kameyama Municipal Medical Centre in Japan from 1 May 2021 to 31 March 2023. We recruited patients who exhibited pitting oedema distal to the knee joint. We excluded patients with oedema in unilateral lower limb, significant asymmetry in oedema between the left and right sides, non-pitting oedema, oedema due to localised skin inflammation or injury (such as cellulitis, burns, and anaphylaxis), undergoing dialysis, and individuals with critical life-threatening conditions who did not have the time for PRT measurement or examination. Based on a prior study by Henry et al., we estimated that our sample size should be more than 126 cases. The calculation method was as follows: first, we inferred data from the plot diagram of their study and categorised it into two groups, a low albumin group with serum albumin levels less than 3.5 g/dl and a normal albumin group with serum albumin levels of 3.5 g/dl or more. We calculated the average PRT scores for each group. The results were 53 and 117 s, respectively, with an average difference in PRT of approximately 64 s between the two groups. The standard deviation for both groups was about 55 seconds, yielding an effect size of 1.0 or more. As the prior study had a small number of cases, we estimated the effect size to be small at 0.5 and calculated the sample size using an alpha value (two-sided) of 0.05 and a beta value of 0.20, resulting in a requirement of more than 63 cases per group.

Data collection: Data collected from the medical interview included age, sex, admission status (inpatient/outpatient), body height, body weight, Birthel Index, Charlson Comorbidity Index, medication, medical history, paralysis, snoring, onset of oedema, and exacerbation of oedema depending on body position or time of day. The variables related to the physical examination included being examined in a sitting or lying posture, skin changes related to lower limb varicose veins [1], soft tissue thickness in the oedema and PRT. Laboratory variables included haematocrit (Hct), albumin, total protein (TP), sodium (Na), potassium (K), blood urea nitrogen (BUN), serum creatinine (sCr), BUN/sCr, glucose, estimated plasma osmolarity (Posm), C-reactive protein (CRP), and brain natriuretic peptide (BNP). The variables being assessed in the transthoracic echocardiography were inferior vena cava (IVC) diameter, respiratory variation of the IVC, estimated transtricuspid pressure gradient (TRPG) and estimated right ventricular systolic pressure (RVSP) [2].

Methods for measuring PRT and soft tissue thickness in the oedema: Lower leg oedema is measured at the midpoint on the rough surface of the tibia at the distal 1/3 height of the line connecting the medial malleolus and medial condyle of the tibia [3], and foot oedema is measured at the dorsum of the 3rd metatarsal head, which is the midpoint of the line connecting the heads of the 1st and 5th metatarsals [4]. For each measurement of soft tissue thickness, the distance from the skin surface to the anterior surface of the tibia was measured for lower leg oedema, and the distance from the skin surface to the head of the third metatarsal was measured for foot oedema, using an ultrasound device. The examiner then firmly pressed the oedema with the thumb for 2 s until a clear indentation remained and subjectively measured the number of seconds (up to a maximum of 600 s) it took for the indentation to completely disappear. This was performed by the same examiner for all patients. If indentations from socks or compression stockings are observed, they were removed and measurements were taken after the indentations have disappeared. The average of the soft tissue thickness at all locations is defined as the 'lower limb soft tissue thickness'. The average of the PRT at the two lower leg locations is defined as the 'lower leg PRT', the average PRT at the two feet locations is defined as the 'foot PRT', and the average PRT at all locations is defined as the 'lower limb PRT'.

Diagnosis of the cause of oedema: Two general practitioners skilled in diagnosing oedema will make judgments based on medical chart data, algorithms for the differential diagnosis of bilateral lower-limb oedema and reviews of each oedema pathology. Please note that the PRT was not used as a reference. Additionally, if necessary for the diagnosis of lower limb oedema, appropriate additional tests (such as urinary protein concentration, lower limb venous ultrasound and abdominal imaging) will be conducted.

References

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2. Rudski LG, Lai WW, Afilalo J et al. Guidelines for the echocardiographic assessment of the right heart in adults: A report from the American Society of Echocardiography. J Am Soc Echocardiogr 2010;23:685–713; quiz 786.
3. Henry JA, Altmann P. Assessment of hypoproteinaemic edema: A simple physical sign. Br Med J 1978 Apr 8;1:890–1.
4. Kogo H, Higashi T, Murata J. Reliability of a new practical evaluation method for pitting edema based on the depth of the surface imprint. J Phys Ther Sci 2015;27:1735–8.