Abstract
Background
Graduated compression stocking (GCS) use during flights demonstrated to positively impact leg oedema. Nevertheless, these data were collected in a single flight, mainly at the ankle, and using greater than 20 mmHg GCS. This investigation reports data from 16 flights in which the same passenger’s leg circumferences variation were assessed wearing non-graduated ankle-sock or a below-knee 15–20 mmHg GCS.
Methods
The limb was divided by the circumferences in eight sectors, every 4 cm, labelled from 1 to 8, starting from the ankle up. The assessment was done at the take-off and after a 4-h flight time, for a total of 16 flights. The subject used non-graduated ankle socks (elastic band at 4 cm from B-point) during the outgoing flight and below-knee GCS (15–20 mmHg) during the return flight. Interface pressure was assessed at the ankle point of minimum girth (B) and ascending proximally every 4 cm (B+cm) for the GCS, and at B and at the elastic band level (B + 4 cm) for the sock.
Results
GCS interface pressure was 13.3 ± 2.5 mmHg in B and 18.1 ± 2.4 mmHg in B + 4 cm. The sock interface pressure was 3.1 ± 0.7 mmHg in B and 8.1 ± 0.9 mmHg at the band level (B + 4 cm). Socks led to a significant total volume increase (117.3 ± 25.8 mL; 5.2% ±1.1%; P < 0.0001). GCS led to a non-significant total volume decrease (–3.1 ± 14.4 mL; –0.1 ± 0.6%; P = 0.3964) and did not allow for volume increase. The different sectors showed a heterogeneous volume variation, not following a precisely graduated or progressive compression profile.
Conclusions
Leg oedema following a 4-h flight is controlled by <20 mmHg GCS. Leg fluids, with and without GCS, are mobilized in a non-graduated profile from the ankle to the knee after prolonged sitting on a plane.
Introduction
The so-called economy class syndrome refers to lower limb venous and lymphatic drainage impairment following prolonged sitting during long distance flights. While an increased oedema formation has been reported in such condition, the pathophysiology of the phenomenon is not fully described and understood yet.1,2
Moreover, a clear unanimously accepted definition of “long-haul” flight is still missing, thus making the topic still in need of data collection. 3
Such topic is of great interest also considering that, according to the Spike Aerospace report, 6 million people are flying every day, thus being potentially exposed to lower limb oedema development. 4
The related oedema has been reported to last up to three days after the flight, thus making the possibility of reducing its occurrence a desirable option. 5
Periodic on board flight leg exercise showed no measurable preventative effect in leg volume increase. 6
According to literature revision performed by Cochrane in 2016, graduated compression stocking (GCS) use during flights demonstrated to positively impact leg oedema. Nevertheless, these data involved different subjects in a single flight, reporting limb circumference variations mainly just at the ankle, most of the time using greater than 20 mmHg GCS.
The same Cochrane revision concluded that low-quality evidence supported the use of GCS for leg oedema reduction, and the reason why such quality is limited is associated with the method that the lower limb volume variation was measured. 7
Another reason for evidence quality limitation is the timing and methodology of the assessment.
For example, one of the major studies using less than 20 mmHg GCS in long flights oedema prevention was the Lonflit 4. In this investigation, GCS (14–17 mmHg) were used starting from 2 to 3 h before the flight, thus introducing the bias of the different muscular activity of the different subjects’ calf pumps and related GCS effect.
Moreover, in a non-standardized way, passengers were suggested to perform exercises, drink water, and avoid salty food during the flight, thus introducing further variability in the data collection because of lack of compliance and homogeneity in the measurements. Last but not least, oedema was measured by a semi-quantitative score, involving subjective report, altering the objective investigation of the venous–lymphatic drainage. 8
The same investigational group reported similar benefits in oedema control by GCS use even with smaller compression doses (11–18 mmHg). Yet, no objective data were reported in lower limb volume and circumferences assessment. 9
Another investigation by the Lonflit 4 authors assessed the impact of 20–30 mmHg GCS on oedema and deep venous thrombosis prevention. Also, in this investigation, no objective measurements of volume and leg circumference were reported for the different leg regions, thus making the evaluation of the specific segmental venous–lymphatic drainage impossible. 10
Mittermayr et al. assessed lower limb volume variation during a 9-h flight, both in patients at risk of venous thrombosis and in healthy subjects. 5 In both groups, a fluid accumulation was reported in the thigh as well as in the leg, yet no specific changes in the different limb segments were investigated, thereby limiting the analysis of the fluid shifts.
In previous investigations, leg fluid accumulation is significantly detectable as early as 4 h, with no significant variations of leg-vessels cross-section diameters and femoral vein flow velocity. 11 This would support that evaluations within a 4-h time period, as during sitting for a flight, may detect possible changes in leg oedema and fluid shifts, and how compression affects these parameters.
Data related to the segmental volume variation during prolonged flights and the related impact of GCS rather than a non-graduated ankle-sock are lacking.
The aim of the present investigation is to report circumferences and volumes of the different leg segments, limiting the potential bias of the study population by analyzing a single healthy subject during 16 standardized flights in a one-year time observation, wearing a non-graduated ankle-sock or a below-knee 15–20 mmHg GCS.
Methods
In a 38-year-old healthy male (body mass index (BMI): 23), right and left leg circumferences were measured every 4 cm, starting from B-point (ankle point of minimum girth) to the knee. The limb was divided by the circumferences in eight sectors named from 1 to 8, starting from the ankle and ascending sequentially for each sector. These circumferences were named as ‘B’ plus the number of centimetres from B-point (B + 4, B + 8, B + 12, B + 16, B + 20, B + 24, B + 28). B + 12 line corresponded to the point in which the Achilles tendon changes into the calf muscles: this point is also named B1 following international consensus. 12 The subject measured the circumferences in a sitting position, performing three assessments per circumference and determined the mean of the three values as final measurement.
The assessment was done at the take-off and after a 4-h flight time, for a total of 16 flights, along a 12 months period. The subject used non-graduated ankle socks with the elastic band at 4 cm from B-point 12 during the outgoing flight, and below-knee GCS (15–20 mmHg, Mediven Active, Bayreuth, Germany) during the return flight. Leg volume was calculated by Kunkhe formula for both total limb and single segments assessment. 13 GCS interface pressure (IP) was assessed before every return flight every 4 cm, in correspondence of the circumference lines measurements in the sitting position. IP was assessed in sitting in B and at the elastic band level for the sock (4 cm from B) before all of the outgoing flights.
In the 4 h of analysis, the passenger fasted and remained seated without performing leg exercises in order to guarantee data homogeneity. Before measuring the leg circumferences at the take-off, the subject wore below-ankle non-compressive socks to maintain homogeneity at the data collection baseline between the evaluation with GCS and the one with ankle-socks.
Statistical analysis
InStat GraphPad (GraphPad Software, Inc, La Jolla, CA, USA) was used for statistical analysis. The data were expressed as mean ± SD, or percentage. Kolmogorov–Smirnov test was used to assess the data distribution.
The differences between GCS IP values, volume and circumference were performed using Student’s t-test for paired or Wilcoxon signed-rank test when appropriate. Pearson correlation coefficient was used to correlate GCS IP and the circumferences values. Statistical significance was defined as P < 0.05.
Results
The mean GCS IP was 13.3 ± 2.5 mmHg in B and 21.1 ± 1.6 mmHg in B + 12; the detailed values of whole measured legs in all points of measurement are reported in Table 1. The sock IP was 3.1 ± 0.7 mmHg in B and 8.1 ± 0.9 mmHg at the band level.
The mean values of all GCS IP, along the assessment circumference lines, every 4 cm.
GCS: graduated compression stocking; IP: interface pressure.
No significant differences were found between right and left leg GCS IP values along the assessment circumference lines (every 4 cm) (Table 2).
The mean GCS IP values in right and left legs, along the assessment circumference lines, every 4 cm.
GCS: graduated compression stocking; IP: interface pressure.
aComparison between right leg and left leg GCS IP values.
Figure 1 shows a moderate correlation between GCS IP values and the circumferences reduction (Pearson’s coefficient: r = 0.4).

Linear correlation between GCS IP values and the circumferences reduction.
Tables 3 and 4 report volumes and circumferences variations in different sectors, respectively.
Volume variation in the different sectors with sock and graduated compression stockings.
GCS: graduated compression stocking.
Note: The leg sectors are numbered from 1 to 8 starting from the ankle, progressing proximally every 4 cm.
In the last row, grey shading indicates the increased volume sectors (1, 3, 4 and 5) highlighting a statistically significant higher increase in sock group than in GCS.
Circumference variation in the different sectors with sock and graduated compression stockings.
GCS: graduated compression stocking.
Note: The leg sectors are numbered from 1 to 8 starting from the ankle, progressing proximally every 4 cm.
Wearing ankle-socks led to a significant lower limb total volume increase (117.3 ± 25.8 mL; 5.2% ± 1.1%; P < 0.0001) after 4-h flights (Figure 2).

Total lower limb variation. Total below-knee volume variation wearing graduated compression stockings (–0.1 ± 0.6; P: ns) or non-graduated compression ankle-socks (5.2 ± 1.1; P < 0.0001).
Wearing GCS led to a non-significant total volume change (–3.1 ± 14.4 mL; –0.1% ± 0.6%; P = 0.3964) (Figure 2).
A sub-analysis was performed comparing only the increased volume sectors (1, 3, 4 and 5, respectively) in the two groups (sock vs. GCS), showing a statistically significantly higher volume variation in the sock group than in the GCS (P < 0.0001)(Table 3).
The different sectors showed a heterogeneous circumference and volume variation in GCS, not following a linear graduation from the ankle towards the knee (Tables 3 and 4; Figure 3).

Percentage volume variation in the different sectors while wearing below-knee GCS. Sectors are numbered from 1 to 8 starting from the ankle, progressing proximally every 4 cm. Interface pressure is reported in correspondence of the different assessment lines.
The socks band significantly decreased the related leg circumference (–2.5% ± 0.8%; P < 0.0001), increasing significantly the below sector volume (10.7% ± 3.2%; P < 0.0001).
Socks sector 4 volume had a higher increase than sector 3 (8.2% ± 3.9% and 6.7% ± 2.6%) (Tables 3 and 4, Figure 4).

Percentage volume variation in the different sectors while wearing non-graduated ankle-sock. Sectors are numbered from 1 to 8 starting from the ankle, progressing proximally every 4 cm. Interface pressure is reported in correspondence of B and B + 4 cm assessment lines – B + 4 cm corresponds to the elastic band position.
After wearing GCS, the greatest segmental volume increase was reported in the lower part of the leg, at sector 2 (2.8% ± 1.9%, P < 0.0001), while at the calf level, the two most proximal segments 7 and 8 showed a significant segmental volume reduction (–1.7% ± 0.9%, P < 0.0001; –1.7% ± 1.5%, P < 0.0001).
No significant differences were reported in right and left volume variations in both groups (GCS: P = 0.2368; sock: P = 0.4310).
Discussion
The present investigation demonstrates that 4-h flights are associated with an increase in below-knee lower limb volume of 5.2% ± 1.1% whenever using non-graduated socks.
Below-knee GCS exerting 15–20 mmHg are able to counteract this volume increase.
The innovative data brought by this investigation, together with the comparison of wearing a normal dress sock with that of wearing a 15–20 mmHg GCS, are the evaluation of the different leg sectors volume and circumference variations.
These data demonstrated that non-graduated socks can generate a tourniquet-like effect.
Indeed, their elastic band performs a compression leading to a significant reduction in the related circumference and to a significant increase in the below sector volume (sector 1).
Interestingly, the sector above the elastic band (sector 2) presents a volume increase percentage that is smaller than the higher sector 3 (–4.8% ± 1.6% vs. 6.7% ± 2.6%, respectively) suggesting that oedema is not generated simply in a gravitational profile from the distal towards the most proximal part of the leg. A pumping effect of the elastic band, favouring drainage of the same sector 2, could be hypothesized, but future investigations are needed to identify the physiological determinants of fluid shifts on the lower limb in prolonged sitting.
Volume variation in the different sectors using GCS showed a non-linear graduated profile with the highest increase in sector 2. It could be hypothesized that different leg sectors have different subcutaneous thickness, thus allowing more fluid accumulation in an area rather than in another. This could be the case of sector 1 (more bony area, smaller volume increase) compared to sector 2 (more subcutaneous tissue, bigger volume increase).
The data are in accordance with previous investigations showing that the IP on the skin can have a variability of up to 44% in the associated pressure at the subcutaneous level, based on the same fat distribution. 14
Calf circumferences and related sectors 6, 7 and 8 volumes decreased significantly using GCS, in accordance with the trend of a progressive compression. The data are in accordance with the IP assessment along the circumferences of the analyzed subject limb.
The data confirm a previous finding of our research group, showing that different lower limb shape can present a variation of up to 54% in GCS pressure gradients, still maintaining an efficacy of the same compression on total leg volume reduction. 15
To our knowledge, there are no available scientific data demonstrating the lower limb volume shifts divided in sectors and in comparison between below-knee GCS and non-graduated dress socks.
The present investigation can offer a basis for future research on effect of various GCS on volume and pressure and in relation to limb shape, both in long-flight and in general pathophysiology of leg oedema formation.
Recently, Olsen et al. published data showing the ankle and calf circumference reduction exerted by 23–32 mmHg below-knee GCS during a single 3-h flight on 34 healthy subjects. 16
In our current study, application of 15–20 mmHg GCS during a 4-h flight was associated with a significant decrease in circumference variation and in sectors volumes at the ankle and calf, yet the total leg volume did not change significantly.
This finding demonstrates the importance of proper assessment of the lower limb volume and not just of the circumferences in non-specific points. Future investigations should adopt a standardized lower limb segmental circumferences and volume assessment protocol to produce homogeneous data collections. Proper sizing of the lower limb, eventually also by advanced 3D software, will be fundamental to deeply understand compression mechanism of action.
The strength of the present investigation is the single subject data collection. Indeed, having one single subject analyzed multiple times allowed the elimination of different subjects bias, such as metabolism, limb shape and length, personal venous and lymphatic drainage variations and muscular activation. This is particularly valuable considering the subject always followed the same in-flight protocol. Limitations of this study include the evaluation of a healthy subject with normal BMI, where differences may result from higher BMI and the presence of cardiovascular diseases and risk factors, assessment of only a single GCS brand and dose, lack of evaluation of individuals with chronic venous disease and post-thrombotic syndrome.
Surely, future larger data collection on different subjects and related limb shapes are needed. Such investigations could also allow evaluation of the eventual clinical benefit of GCS use during prolonged sitting. The single patient nature of the investigation did not allow assessment of the GCS impact on symptomatology and general feeling because of the non-blinded nature of the investigation.
Recently published evidence suggest that sitting for 3 h, using 29 hecot-Pascal GCS, significantly increases parasympathetic activity and comfort feeling. 17
Further investigations are needed to properly assess the GCS clinical and psychological effect during prolonged flights. These data will also be fundamental to properly develop future international guidelines and recommendations on the topic. Indeed, in 2011, British Journal of Haematology published guidelines on travel-related venous thrombosis, pointing out that there is no recommendation to the global use of GCS for all long-distance travellers (GRADE 1C). At the same time, the document indicated that travellers at high thrombotic risk should wear a well-fitted GCS for longer than 3-h flights (GRADE 2B). 18
The following year, the American College of Chest Physicians indicated the use of 15–30 mmHg GCS for high-risk patients flying for a prolonged time (GRADE 2C): for all the others subjects, GCS were not recommended (GRADE 2C). 19 However, the National Institute for Health and Care Excellence guidelines recommend GCS use for all subjects at thrombotic risk. 20 Interestingly, the European guidelines indicate GCS use for patients at thrombotic risk with a GRADE 2B, yet they also indicate the use of GCS in subjects at risk of developing oedema (GRADE 1B), which is indicated during prolonged flights. 21
In conclusion, the present work offers a first step forward in evidence-based data collection in the intriguing topic of prolonged flights oedema and in the pathophysiology investigation on the different sectors of fluid distribution. These preliminary data support the notion for specifically oriented graduated compression profiles, acting on the area more prone to fluid accumulation, while providing further information on the poorly understood mechanisms of lower limb fluid accumulation and the effects of GCS on lower limb fluid dynamics.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethical approval
A specific ethics approval was not required since the study included non-invasive measurements in a self-reporting healthy volunteer.
Guarantor
SG.
Contributorship
SG conceived and designed the study, researched literature and collected data and wrote the first draft of the manuscript. GM was involved in data analysis, writing and critical review of the manuscript. JR was involved in writing and critical review of the manuscript. EMa was involved in statistical analysis and critical review of the manuscript. YWC was involved in data analysis and critical review of the manuscript. TL was involved in data analysis and manuscript preparation. EM was involved in protocol development, data analysis, manuscript critical review and preparation. All authors reviewed, edited the manuscript and approved the final version of the manuscript.
Acknowledgements
The abstract of the present work has been accepted as oral presentation at the 2019 International Union of Phlebology Meeting (Krakow, Poland; 25–27 August 2019).
