ISSN 0030- 6096

O S A K A
C I T Y

Vol.

67

No.2

M E D I C A L

2021

J O U R N A L

V o l . 6 7 ,N o . 22 0 2 1

PUBLISHED BYOSAKA CITY MEDICAL ASSOCIATIONOSAKA JAPANOsaka City Medical Journal
Vo l . 6 7 , N o . 2 ,December 2021

CONTENTS
page
High Calorie Diet, Low Body Weight and Hypothermia Limit Body Weight
Gain in Hospital Treatment for Anorexia Nervosa-restricting TypeKAZUYA NISHIMOTO, TSUNEO YAMAUCHI, TOMOKO HARADA,SAORI MIYAMOTO, MIHOKO HONDA, TAKUMI MATSUZUKA,
and KOKI INOUE･･･････････････････････････････････････････････････････････････････････････････････････････ 57
Primarily Outcome Report of Our Updated Structural Strategy for Treating
Patients with Acute Respiratory Distress Syndrome Following
Corona Virus Disease 2019 during the Third Pandemic Phase in JapanKENICHIRO UCHIDA, KENJI MATSUO, SAE KAWATA,
AYAKO KIRITOSHI, RYO DEGUCHI, HOSHI HIMURA,
MASAHIRO MIYASHITA, KATSUMI YAMAMOTO, SHINICHIRO KAGA,TOMOHIRO NODA, TETSURO NISHIMURA, HIROMASA YAMAMOTO,
and YASUMITSU MIZOBATA ････････････････････････････････････････････････････････････････････････････ 69
An Analysis of Compensatory Trunk Movements in Shoulder Joint Movements:
Application to Healthy Individuals and Patients after Shoulder Joint Surgery
TAMOTSU NAKATSUCHI, MITSUHIKO IKEBUCHI,
TAKAHIRO NISHINOHARA, SHIGEYOSHI NAKAJIMA,
and HIROAKI NAKAMURA･････････････････････････････････････････････････････････････････････････････････ 81― Case Report ―Orbital Venous Malformation with Obscure Clinical Symptoms Diagnosed byContrast-enhanced Magnetic Resonance Imaging in a Different Body Position
AKIKA KYO, YUSAKU YOSHIDA, MIZUKI TAGAMI,MASAO HAMURO, and SHIGERU HONDA･･････････････････････････････････････････････････････････････ 91

Osaka City Med. J. Vol. 67, 57-68, 2021

High Calorie Diet, Low Body Weight and Hypothermia Limit
Body Weight Gain in Hospital Treatment for
Anorexia Nervosa-restricting TypeKAZUYA NISHIMOTO, TSUNEO YAMAUCHI, TOMOKO HARADA, SAORI MIYAMOTO,MIHOKO HONDA, TAKUMI MATSUZUKA, and KOKI INOUE
Department of Neuropsychiatry, Osaka City University Graduate School of Medicine

Abstract
Background
There are considerable individual differences in how body weight increases in response to calorie
intake in hospitalized patients with anorexia nervosa (AN); however, the extent of the factors
inﬂuencing weight gain remain unclear. Thus, this study aimed to clarify the relationship between
body mass index (BMI) gain in hospitalized female AN patients and factors including calorie intake,body weight, and body temperature.
Methods
Subjects were 56 female anorexia nervosa-restricting type (AN-R) patients who had been
hospitalized for at least 60 days. Age, height, body weight, body temperature, blood test results, andcalorie intake were surveyed. BMI gain was deﬁned as the difference when predicted BMI calculatedusing calorie intake beginning on day 30 of hospitalization was subtracted from actual BMI on day
60. The effects of calorie intake, body weight, body temperature, presence of liver dysfunction, age,and disease duration were explored using multiple regression analysis.
Results
With regard to BMI gain, the higher total calorie intake, lower weight on day 30, and lower mean
body temperature during the latter period of hospitalization were, weight gain was found to fallsignificantly below the expected level. Relationships were not found with presence of liver
dysfunction, age, and disease duration.
Conclusions
It is likely that weight did not increase as much as expected from calorie intake in AN patientswith severe low body weight due to physical abnormalities. We must consider the extent of theirrecovery from critical physical issues.
Key Words: ‌Weight gain; Anorexia nervosa-restricting type; Body mass index; Calorie
intake; Hypothermia
Received September 4, 2020; accepted January 12, 2021.
Correspondence to: Kazuya Nishimoto, MD.
Department of Neuropsychiatry, Osaka City University Graduate School of Medicine,
1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
Tel: +81-6-6645-3821; Fax: +81-6-6636-0439
E-mail: k.nishimoto.1985@gmail.com- 57 -

Nishimoto et al

Introduction
Anorexia nervosa (AN) is an eating disorder (ED) with a high mortality rate resulting from severe
low body weight caused by refusal of food1-4). While eating disorders are primarily treated on an
outpatient basis, inpatient treatment is recommended for patients in critical physical condition due
to their low body weight5-7). The goal of hospital treatment is to manage physical condition while
increasing body weight by returning to an appropriate intake of nutrients. Weight at discharge is an
important prognostic factor for long-term prognosis with higher weight shown to lead to a better
prognosis 8-10). Meanwhile, low body weight at the time of admission is also linked to extended
hospitalization11). However, it is best to avoid extended hospital stays because of the mental stress onpatients and ﬁnancial reasons. Thus, effective weight gain during hospitalization is essential. In
recent years, rapid refeeding for the purpose of efficient weight gain has become the standard
treatment, and eventually patients may consume nearly 3000 kcal/day12,13).
Hospitalized AN patients show individual differences in the speed and level of weight gain
depending primarily on calorie intake12-15). However, clinically, weight gain can be smaller or evenlarger than the amount expected based on calorie intake. It is unclear whether this variance takes
place as a result of differences in the physical condition of individual patients, or due to resistance totreatment that has gone unnoticed by medical workers such as excessive activity, discarding of food,or self-induced vomiting, which are commonly seen during hospitalization. Clinicians may sometimes
suspect that these disappointing results are due to a lack of motivation for treatment or resistance on
the part of the patient, thereby unfortunately worsening the relationship between doctor and patient.
Nonetheless, there remains insufficient research clarifying factors related to weight gain duringhospitalization.
Metabolic amount, which is inﬂuenced by a multitude of factors, is generally considered to have amajor involvement in weight gain. In AN patients, a condition in which patients have severely low
body weight, basal metabolic rate (BMR) is low16-18). Additionally, aging is also associated with
progressive declines in BMR19,20). Further, the endocrine system has a major impact on metabolism,and endocrine abnormalities are common in chronic AN patients21-24). Body temperature has areciprocal relationship with metabolism 25), and it is no surprise that most AN patients arehypothermic7,26,27). Body temperature are reversible and can all be improved in AN patients byreturning to proper nutrition through treatment26,28).
Organ dysfunction is another factor involved in weight gain. Liver dysfunction in particular is aform of organ dysfunction characteristic to low body weight AN6,7,29,30). In this context, research has
shown that the amount of weight gain after admission is lower than normal in AN patients with liver
dysfunction30). AN patients are also known to frequently exhibit digestive dysfunction31-34). Further, it
is likely that, as the duration of AN increases, organ dysfunction and physical complications will
become more serious7).
In clinical settings, it is not uncommon to see sudden and drastic increases or decreases in weightat the start of hospitalization due to dehydration or edema present at admission14,35-38). Yet, most past
research on weight gain during hospitalization have used body weight and body mass index (BMI)
measurements taken on the day of admission11-15,30,35-40). This leads to several problems. For example,
the lower body weight is on the day of admission, the higher the rate of increase in body weight and
BMI will be thereafter11). However, these studies did not consider that weight gain changes over timein accordance with individual calorie intake levels.

- 58 -

Weight Gain and Its Limiting Factors

In the present study, we decided the starting day as the one at which the irregular body weightﬂuctuations found at the start of hospitalization had largely disappeared and considered BMI gain
thereafter by subtracting the predicted BMI estimated using calorie intake from the actual BMI
measured on day 60 of hospitalization. Subjects were patients with anorexia nervosa-restricting type
(AN-R). Because these patients do not binge-eating and purging, their body weight ﬂuctuations at
the start of hospitalization are lesser than those in patients with AN binge-eating/purging type (ANBP)37). This study aimed to clarify the relationship between BMI gain and factors hypothesized toinﬂuence it, namely, calorie intake, body weight, body temperature, presence of liver dysfunction, age
at admission, and disease duration.

Methods
Patients
This was a retrospective cohort study based on the medical records of eating disorder patients
admitted to the neuropsychiatry ward at Osaka City University Hospital between April 1, 2012 andMarch 31, 2018. There were 143 patients satisfying the Diagnostic and Statistical Manual of Mental
Disorders, 5th ed. (DSM-5)41) diagnostic criteria for AN, of which 87 (60.8%) were classiﬁed as AN-R,
and 56 (39.2%) were classified as AN-BP. Of those with AN-R, 29 patients (33.3%) with ahospitalization period of under 60 days and 2 patients (2.3%) who were male were excluded for an
end total of 56 subjects (64.4%).
Procedure
Age at admission, disease duration, height at admission, body weight, body temperature, blood
test data, and daily calorie intake from the day of admission to day 60 of hospitalization wereextracted from subjects medical records. Body weight was measured and recorded every 1-7 days
according to the patient s physical condition. Axillary body temperature, which was taken every
morning, was averaged for every 10 days after hospitalization. Patients with maximum values of
AST or ALT recorded as being above grade 3 (either AST ＞175 U/L or ALT ＞150 U/L), based on the
Common Terminology Criteria for Adverse Events (CTCAE) version 5.042) standards, during the 60days of hospitalization were classiﬁed as having liver dysfunction. The daily calorie intake is basedon medical records. The amount of carbohydrates, proteins, and fats in each meal was measured by
the dietitian, and calories were calculated using the modified Atwater system (4 kcal/g forcarbohydrates and proteins, 9 kcal/g for lipids)43). Patients were required to consume all of the foodprovided, and the percentage of consumption was recorded. Calories for nasogastric tube feeding andintravenous drip were added to the calorie intake, if performed.
MeasuresDay 30 of hospitalization was used as the starting day for comparison, when body weight gain was
judged to have stabilized. BMI gain was defined as the BMI (kg/m2) difference obtained when
predicted BMI calculated using calorie intake was subtracted from actual BMI on day 60 of
hospitalization. Estimated body weight was calculated by adding the expected amount of weight gain
(calculated from total calorie intake during that period) from the initial day to the next day that bodyweight was measured. When calculating expected weight gain, every 7000 kcal remaining after
subtracting the patient s total energy expenditure from the total calorie intake was established ascorresponding to 1 kg of body weight 43,44). Total energy expenditure was calculated by multiplying
BMR and activity factors. There is no ideal formula for calculating BMR for low body weight AN. In- 59 -

Nishimoto et al

this study, we adopted the Ganpule equation [BMR (kcal)＝{0.0481×body weight (kg)＋0.0234×height(cm)−0.0138×age (years)−0.9708}×1000/4.186], which includes the basic parameters that constitutemost formula for BMR45). Activity factors were determined by the extent of activity while hospitalized(confined to bed 1.2, out of bed 1.3)46). The extent of activity was always strictly controlled in theclosed ward. Patients with extremely low body weight were conﬁned to bed, and out of bed activities
were permitted according to the degree of weight gain.
Statistics
Mean body temperature, BMI, and body weight after admission were analyzed using repeatedmeasures ANOVA and the Bonferroni post hoc test. To determine the validity of the starting day,when weight gain after hospitalization was thought to have stabilized, the error between BMI derived
using the connection between BMI at admission and BMI on day 60 of hospitalization and actual BMI
was analyzed using a chi-squared test. Factors impacting BMI gain were explored using multiple
regression analysis. Concerning independent variables, age at admission was entered using the force
entry method, while total calorie intake, weight on day 30 of hospitalization, mean body temperature
over days 1-10 of hospitalization, mean body temperature over days 51-60 of hospitalization, presenceof liver dysfunction, and disease duration were entered using the stepwise method. A two-tailed pvalue of less than 0.05 was considered signiﬁcant. Data were analyzed using SPSS26.0 for Mac OS X
(SPSS Japan, Tokyo, Japan). Due to the retrospective nature of this study, personal data were
protected and individuals were not identiﬁed; informed consent could not be obtained. The research
protocol was reviewed and approved by the Ethics Committee of Osaka City University.

Results
Subjects mean age at admission was 18.04±7.73 years. Grouping by age reveals that mostparticipants were young, with 18 patients under the age of 15 (32.1%), 26 between the ages of 15 and19 (46.4%), 6 between the ages of 20 and 24 (10.7%), 2 between the ages of 25 and 29 (3.6%), and 4
aged 30 or above (7.1%). Mean BMI at admission was 11.73±1.60, and 55 subjects (98.2%) had a BMI
below 15, which is classiﬁed as most severe in the DSM-5 diagnostic criteria. The disease durationfrom onset to admission was less than 1 year for 17 subjects (30.0%) and less than 3 years for 45
subjects (80.0%), but was over 20 years for 2 subjects (3.6%). Mean body weight at admission was
27.73±4.80 kg. This was on mean 13.89±7.22 kg lower than their weight before the onset of EDs,
and body weight had dropped by over 10 kg for 36 patients (62.3%). During the 60 days of
hospitalization, mean maximum values of AST was 112.13±371.25 U/L, and mean maximum valuesof ALT was 152.45±326.23 U/L. Fourteen patients had liver dysfunction. Of these, 5 satisﬁed thecriteria for both AST and ALT, 9 for ALT alone, and none for AST alone. Mean total calorie intake
during the 60 days of hospitalization was 108.21±23.21 Mcal (protein 18.10±4.62 Mcal; fat 24.02±
6.87 Mcal; carbohydrates 66.10±13.61 Mcal). Mean total calorie intake from day 30 to 60 was 65.43±13.30 Mcal (protein 10.17 ±2.64 Mcal; fat 14.01 ±4.37 Mcal; carbohydrates 40.42 ±10.43 Mcal).

(Table 1)
Table 2 shows body weight and BMI every 10 days, and mean body temperature for each 10-day
period after admission. With respect to mean body weight and BMI, comparison between measuresat admission and on day 60 of hospitalization revealed that both increased signiﬁcantly by 4.86 kg in
weight and 2.06 kg/m2 in BMI, respectively. There were substantial individual differences in weightand BMI gained by each subject over the 60-day hospitalization period with body weight changes- 60 -

Weight Gain and Its Limiting Factors
Table 1. ‌Clinical characteristics
Toal (N＝56)
18.04±7.73

Age (years)aHeight (cm)a153.60 (150.58, 157.03)
27.73±4.76

Body weight (kg)a

11.73±1.59

BMI (kg/m )2 aDisease duration (years)b

1.50 (0.92, 2.43)
15.02±3.93

Age of onset of EDs (years)
Weight before the onset (kg/m2)

41.63±8.92

Liver dysfunctionc

14/56 (25)108.21±23.20

Total calorie intake (Mcal)c

Date are means ±SD, median (25 percentile, 75 percentile), or n (%).
Patients with maximum values of AST or ALT recorded either AST ＞175 U/Lor ALT ＞150 U/L were classiﬁed as having liver dysfunction.
aat admission. b from onset to admission. c during the 60 days of hospitalization.
BMI, body mass index; and ED, eating disorder.

Table 2-1. ‌Body weight and BMI every 10 days after admission

Body weight (kg)
Mean＊a(SD)
BMI (kg/m2)
Mean＊a(SD)

Day 1

Day 10Day 20Day 30Day 40Day 50Day 60

27.73
4.76

28.90
5.15

29.29
5.01

30.00
5.07

30.98
5.14

31.95
5.28

32.59
5.37

11.73
1.59

12.21
1.77

12.39
1.73

12.69
1.77

13.11
1.79

13.52
1.84

13.79
1.86

Table 2-2. ‌Mean body temperature for each 10-day period after admission
Days 1-10

Days 11-20

Days 21-30

Days 31-40

Days 41-50

Days 51-60

36.48
0.35

36.64
0.28

36.68
0.27

36.67
0.23

36.72
0.29

36.69
0.27

Mean body temperature (℃)
Mean＊b(SD)

n＝56, ＊p＜0.05. (Statistically signiﬁcant)aBody weight and BMI increased signiﬁcantly every 10 days after admission, except between day 10 and day 20.
b
Mean body temperature over days 1-10 of hospitalization was signiﬁcantly lower than other periods. BMI, body massindex.

ranging from −0.90 kg to ＋10.00 kg and BMI changes ranging from −0.39 kg/m2 to ＋4.44 kg/m2. Whilesome patients did show sudden and drastic weight gain or loss at the start of hospitalization, only one
patient lost weight between day 30 and day 60 of hospitalization. In order to select a starting date at
which the irregular ﬂuctuations in body weight at the start of hospitalization had abated and BMI
gain had stabilized, we calculated the chi-squared value for the error between actual BMI and BMI
derived using the connection between BMI at admission and BMI on day 60 of hospitalization. The
chi-squared value increased from admission onward, peaking at 5.35 on day 12 before decreasing
continuously until day 60. Values were 4.07 on day 10, 1.22 on day 20, and 0.65 on day 30. The error- 61 -

Nishimoto et al

had largely disappeared on day 30. Thus, day 30 was decided as the starting day. Body temperatureﬂuctuated greatly day to day and was therefore represented with an average every 10 days. Meanbody temperature over days 51-60 during the latter period of hospitalization increased signiﬁcantly
to 36.69±0.27℃ compared to 36.48±0.35℃ over days 1-10 during the early period of hospitalization.
The relationships between total calorie intake and BMI gain were illustrated as scatter plots in
Figure 1. The relationships between mean body temperature and BMI gain were illustrated as
scatter plots in Figure 2. The relationships between body weight on day 30 of hospitalization and
BMI gain were illustrated as scatter plots in Figure 3. As these scatterplots demonstrate linear
relationships, a multiple regression analysis was performed.
Table 3 shows the results of multiple regression analysis using the force entry and stepwise
methods for factors impacting BMI gain. Although a signiﬁcant relationship was not found for age at
admission (β＝0.16, p＝0.11), signiﬁcant relationships were found for total calorie intake (β＝−0.74,
p＜0.01), body weight on day 30 of hospitalization (β＝0.27, p＜0.05), and mean body temperature overdays 51-60 of hospitalization (β＝0.43, p＜0.01). In the final model, the normality of the residuals
were analyzed using the Shapiro-Wilk test and conﬁrmed as p＝0.764. All VIFs were less than 10.0,
so there were no multicollinearities. The Durbin-Watson ratio was 1.724 and there were no outliers.
This study concludes that a higher total caloric intake was associated with a lower BMI gain
compared to the predicted gain, while a higher mean body temperature during the latter period of
hospitalization and a higher starting weight were associated with a higher BMI gain. However, mean
body temperature over days 1-10, presence of liver dysfunction, age at admission, and disease
duration were not found to be signiﬁcantly associated with BMI gain.

Figure 1. The relationship between total calorie intake and body mass index (BMI) gain.

- 62 -

Weight Gain and Its Limiting Factors

Figure 2. The relationship between mean body temperature over days 51-60 and body mass index (BMI) gain.

Figure 3. The relationship between body weight on day 30 of hospitalization and body mass index (BMI) gain.

- 63 -

Nishimoto et al
Table 3. ‌The results of multiple regression analysis using the force entry and stepwise methods forfactors impacting BMI gain
95% conﬁdence interval for B
Lower
Upper
R2
β
limit
limit

B
Age at admission (years)−0.0020.02＊−0.017−0.009

＊

0.37

0.97

＊

0.004

0.04

0.01

0.16

−0.013−0.74

Mean body temperature over days
51-60 of hospitalization (℃)

0.67

0.43

Body weight on day 30 of
hospitalization (kg)

0.02

0.27

Total calorie intake (Mcal)a

0.54

Adjusted
R2

F

0.51

15.11

＊

Concerning independent variables, age at admission was entered using the force entry method, while total calorie
intake, weight on day 30 of hospitalization, mean body temperature over days 1-10 of hospitalization, mean bodytemperature over days 51-60 of hospitalization, the presence of liver dysfunction, and disease duration were enteredusing the stepwise method. The ﬁnal model accounted for 51% (F ＝15.11, p＜0.01) of the variance.
n＝56, ＊p＜0.05. (Statistically signiﬁcant) aduring the 60 days of hospitalization. B, unstandardized coefﬁcient; β,standardized partial regression coefﬁcient; and BMI, body mass index.

Discussion
This study aimed to clarify the relationship between BMI gain and calorie intake, body weight,
body temperature, presence of liver dysfunction, age at admission, and disease duration in
hospitalized patients with AN-R. As a result, BMI gain was found to be signiﬁcantly lower than thepredicted amount when total calorie intake during hospitalization was higher, weight on day 30 of
hospitalization was lower, and mean body temperature over days 51-60 during the latter period of
hospitalization was lower. Meanwhile, presence of liver dysfunction, age at admission, and disease
duration were not shown to have a signiﬁcant relationship with BMI gain.
Generally, it can be assumed that consuming more food will lead to more weight gain. Highcalorie diet on admission was reported to be associated with rapid recovery12,15). In this study, ANpatients consumed enough food to have a calorie surplus, and indeed, most patients gained weightover the hospitalization period. However, BMI gain was found to fall below the level expected whentotal calorie count was higher.
It is worth noting that impaired digestion and absorption of nutrients in AN patients may have
impacted this result. In this context, research using eating disorder model mice demonstrated that
increased colonic permeability and histological alterations̶caused by the eating disorder̶result in
impaired absorption of nutrients47). These findings suggest that a similar change also occurs inhuman AN patients. Moreover, food spending a longer period of time in the stomach due toweakening of the gastrointestinal tract and reduced digestive function caused by issues such as
constipation are inevitable complications in clinical AN patients32-34). In this study as well, the amountof food provided during hospitalization likely surpassed the capacity for digestion and absorption of
AN patients, who have a poorer ability to digest and absorb nutrients than healthy individuals.
Meanwhile, reduction in the amount of energy necessary to maintain functioning will increase thecalorie surplus, which makes it easier to gain weight. This is largely inﬂuenced by BMR which, as
demonstrated by the Ganpule equation, increases with body weight45). In the past, some studies usedindirect calorimetry to measure basal metabolism17,18,21,28). However, the method of estimating the- 64 -

Weight Gain and Its Limiting Factors

predicted body weight and comparing with the measured body weight as in this study has not beenused in previous studies. In this study, basal metabolism increases with weight gain over the courseof treatment as in previous studies. However, this is contrary to our ﬁnding that higher body weightincreased the likelihood of weight gain. In the body composition of AN patients, FM is extremely low,meaning that the ratio of FFM is high relative to that of healthy individuals37). When AN patients
rapidly gain weight over a short period by increasing food intake, the formation of tissues with a high
BMR, like muscle16-18), is likely to be limited by the hospital environment in which patients do not
exercise. Thus, the BMR for AN patients in the process of recovery with a relatively high body weight
may have been lower than the BMR calculated from their actual body weight in this study. On theother hand, past studies have found that AN patients preferentially recovered FFM, and that FFM
requires less energy than FM to be increased48). Thus, future research would beneﬁt from measuring
the FM and FFM comprising subjects body compositions.
Body temperature is thought to be an indicator indirectly reflecting BMR 25). Moreover, AN
patients are known to often become hypothermic7,26,27). In clinical settings, patients often temporarily
experience drastic ﬂuctuations in body temperature, particularly at the start of hospitalization, due
to the impact of factors such as circulatory dynamics and dehydration accompanying changes in theirdiet and living environment49). Increase in body temperature during hospitalization represents anincrease in BMR and was hypothesized to inhibit weight gain, but our results showed that the
opposite is true. Although there has been minimal research on body temperature changes in AN,
Belizer CM et al suggested that recovery from hypothermia in AN may be a predictor of physicalrecovery26). In the present study, mean body temperature increased signiﬁcantly over time from theearly period of hospitalization. Thus, high body temperature during the latter period of
hospitalization may have represented physical improvements including recovery from impaired
digestion, absorption, and organ dysfunction.
The various organ dysfunctions that often complicate AN have been shown to accelerate
metabolism46,50,51) and may reduce excess calories used for weight gain. Liver dysfunction is seen at aparticularly high frequency in AN30,31). Additionally, it has been reported to make weight gain moredifficult than normal30). The extent of organ dysfunction is incorporated into the equation for
calculating basal metabolism as stress factors46,50,51). However, there is no clear consensus regarding
stress factors. For example, some ﬁndings to the contrary indicate that there is only one or less stressfactors in a state of chronic malnutrition50). In the present study, when calculations were performed
with stress factors of 1, presence of liver dysfunction was not found to have a signiﬁcant relationshipwith BMI gain, and thus, presence of liver dysfunction was not found to impact basal metabolism. In
determining the stress factors, it is essential to consider the complex relationships between various
factors including organ dysfunction, particularly liver dysfunction.
Although BMR decreases with aging19,20), age at admission was not signiﬁcantly associated withBMI gain in the present study. Past studies exploring age and disease duration have also been
unable to identify signiﬁcant associations 38,39,52). The fact that most participants were in their 20s or
younger and had a disease duration of less than three years may partially explain why a signiﬁcantrelationship was not found.
The present study has several limitations. Because there is no formula for calculating basal
metabolism indicated for extremely low body weight AN, the Ganpule equation validated in patientswith BMI 16.5 to 36.4 kg/m2 was utilized. However, the mean BMI of the patients in this study was- 65 -

Nishimoto et al

lower, so its suitability may be drawn into question. Additionally, it would have been necessary tomeasure gastrointestinal symptoms such as diarrhea in order to clarify the presence ofmalabsorption. It also would have been optimal to carry out measurements and tests evaluating bodytemperature and liver dysfunction with more meticulous methods and timings. Further, there were
only 56 subjects. Analysis of a larger sample may have shown relationships not detected in thepresent study. Moreover, AN patients resistant to weight gain are often observed resisting treatment
by methods such as discarding food or vomiting while under hospital care. Although subjects
behaviors were carefully monitored during the hospitalization period, the possibility that somesubjects did not consume all the food provided cannot be completely ruled out.
In conclusion, this study found that individual physical factors may impact BMI gain duringhospitalization in AN-R patients. Therefore, we must consider the extent of their recovery fromcritical physical issues. The results of the present study are valuable in that they encourage
clinicians to avoid suspecting patients of behaviors deviating from their treatment plan when weightgain does not match calorie intake in the inpatient treatment of AN. Thus, it is hoped that future
research can shed further light on the factors involved in weight gain and their impact.
Acknowledgments
All authors have no COI to declare regarding the present study.
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Osaka City Med. J. Vol. 67, 69-79, 2021

Primarily Outcome Report of Our Updated Structural Strategy for
Treating Patients with Acute Respiratory Distress Syndrome
Following Corona Virus Disease 2019
during the Third Pandemic Phase in JapanKENICHIRO UCHIDA, KENJI MATSUO, SAE KAWATA, AYAKO KIRITOSHI, RYO DEGUCHI,HOSHI HIMURA, MASAHIRO MIYASHITA, KATSUMI YAMAMOTO, SHINICHIRO KAGA,TOMOHIRO NODA, TETSURO NISHIMURA, HIROMASA YAMAMOTO, and YASUMITSU MIZOBATA
Department of Traumatology and Critical Care Medicine,
Osaka City University Graduate School of Medicine

Abstract
Background
The management of acute respiratory distress syndrome (ARDS) induced by corona virus disease2019 (COVID-19) continues to be challenging, and mortality remains uncontrolled in several
countries. After the first and second pandemic phases during approximately March 2020 to June
2020 in Japan, the in-hospital mortality of our patients with ARDS remained high at 33.3%, so weupdated and modiﬁed our treatment strategy. The aim of this study was to assess our institutional
treatment strategy and its outcomes in the third pandemic phase of COVID-19 in Japan.
Methods
This was a single-center, retrospective study, and all patients admitted during October 2020 toMarch 2021 due to ARDS following COVID-19 were reviewed.
Results
During the study period, 56 patients were managed under mechanical ventilation due to
COVID-19 concomitant with ARDS. Their median age was 73 (66-80) years old and 67.9% were male.
The P/F ratio at the time of admission was 170 (132-222). The median Sequential Organ Failure
Assessment score was 12 (12-14), and two patients required extracorporeal membrane oxygenation.
Our modiﬁed structural strategy with aggressive administration of muscle relaxant drugs to prevent
self-inﬂicted lung injury achieved extubation in 30 patients and successfully weaned from ventilationin 36 patients. The total in-hospital mortality rate during the study period was 16.1%.
Conclusions
Our modiﬁed intensive care strategy for ARDS following COVID-19 achieved improved outcomes.

Received March 24, 2021; accepted June 8, 2021.
Correspondence to: Kenichiro Uchida, MD, PhD, FACS.
Department of Traumatology and Critical Care Medicine, Osaka City University Graduate School of
Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
Tel: +81-6-6645-3987; Fax: +81-6-6646-3988
E-mail: cvs.uchida@gmail.com- 69 -

Uchida et al

Preventing self-inﬂicted lung injury by using muscle relaxant drugs appears to be a key tactic oncepatients require mechanical ventilatory support.
Key Words: ‌ARDS; COVID-19; Mortality; Muscle relaxant drugs; P-SILI

Introduction
The management of severe acute respiratory distress syndrome (ARDS) induced by corona virus
disease 2019 (COVID-19) continues to be a difﬁcult situation, and mortality remains uncontrolled inseveral countries1,2). During the ﬁrst and second pandemic phases from approximately March 2020 toJune 2020 in Japan, we managed the severity of compromised patients especially by taking care toprevent ventilator-associated lung injury as globally prescribed3-5), but it was sometimes difﬁcult tocontrol self-inspiration efforts of the patients, which resulted in hyper tidal volume ventilation eventhough peak intratracheal pressure was controlled. In the previous pandemic phase in Japan, ﬁnal
in-hospital mortality after following our institutional stepwise strategy for ARDS following COVID-19
was high at 33.3% 6). To improve this rate, and because some previous reports recommended
prioritization of controlling patient self-inflicted lung injury (P-SILI) in ARDS management7-9), we
modiﬁed our respiratory management strategy to aggressively administer muscle relaxant drugs tolimit spontaneous breathing. The aim of this study was to assess our updated treatment approachfor the patients with ARDS related to COVID-19.

Methods
In this single-center, retrospective review, we assessed the records of all patients who had been
admitted to the Trauma and Critical Care Center of Osaka City University Hospital because of asevere respiratory condition following COVID-19 from October 2020 to March 2021. We excluded thepatients who had not needed mechanical ventilation support entirely or who had been in
cardiopulmonary arrest (systolic blood pressure ＜40 mm Hg) on arrival to hospital. The patients
who were intubated and placed on positive mechanical ventilation because of ARDS were reviewed
and evaluated for outcomes and complications. The classiﬁcation of ARDS severity was according to
the Berlin deﬁnition10). An outline of our modiﬁed stepwise treatment approach for ARDS following
COVID-19 is shown in Figure 1.
Treatment for COVID-19
In this third domestic pandemic phase, for the patients with polymerase chain reaction (PCR)positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we basically use
remdesivir for the ARDS patients and favipiravir for the patients with decreased renal function or
chronic kidney disease. Remdesivir was administered at an initial dose of 200 mg on the ﬁrst day
and continued at 100 mg per day for the next 10 days11,12). The initial dose of favipiravir was 3600 mg
on the ﬁrst day and 1600 mg per day for the next 14 days13).
Considering the potential for the patients to acquire community-acquired pneumonia, ceftriaxone
was administered concomitantly until the sputum culture was conﬁrmed. At the time the sputum
culture was confirmed to be negative or show normal flora, we terminated this antibiotic, and if
causative bacteria such as methicillin-resistant Staphylococcus aureus were detected or had alreadybeen detected at the previous hospital, we added or continued drugs susceptible for these bacteria.
Respiratory management focusing on patient self-inflicted lung injury
During the previous ﬁrst and second pandemic phases, as there were many reports warning of- 70 -

Outcome of COVID-19 with ARDS in Pandemic Phase 3

Figure 1. Our stepwise approach to treating ARDS secondary to COVID-19. ARDS, acute respiratory distresssyndrome; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; P-SILI,
patient self-inﬂicted lung injury; PEEP, positive end-expiratory pressure; P/F, PaO2/FiO2 ratio; PIP, positive inspiratory
pressure; and V-V/V-A ECMO, veno-venous/veno-arterial extracorporeal membrane oxygenation.

adverse complications of thromboembolism as a result of hyper-coagulopathic issues related to
COVID-1914-16), we dared to taper sedative drugs once a day to assess the level of consciousness and toevaluate neurological deﬁcits of the patients. In the current study period, however, we converted to a
strategy of preventing P-SILI as much as possible by administering muscle relaxant drugs for theﬁrst 48 hours of ventilatory support. During this period, the spontaneous respiration of the patientswas completely suppressed and intratracheal pressure was strictly monitored. However, if thepatients had already been clearly concomitant with aspiration pneumonia or under hemodynamicallyunstable at the time of admission, we did not dare to administrate muscle relaxant drugs for thesepatients. The tidal volume was strictly limited to under 6 mL/kg of ideal body weight by using thepressure-regulated volume control (PRVC) ventilation mode 4,17). To prevent the occurrence ofventilator-induced lung injury, maximum airway pressure was controlled so as not to exceed 30 cm
H 2O18). After muscle relaxant drugs were stopped, if the patients showed poor synchronization withthe ventilator, fentanyl was replaced with morphine sulfate 0.6 mg/kg/hour to control excess
spontaneous respirations. We additionally monitored both static and dynamic lung compliance andalso airway occlusion pressure at 100 msec (P0.1), which allowed us to evaluate the inspiratory effortsof the patients during spontaneous respiration. If the patient required mechanical ventilatory
support for more than 14 days, we performed a tracheostomy and continued to try weaning thepatient ventilation support.

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Uchida et al

Infusion management
Infusion control was based on serum lactate level, maintenance of stroke volume variation
between a range of 10%-18%, and maintenance of the length of the left ventricular enddiastolic
diameter between a range of 35-40 mm and that of the inferior vena cava diameter between a rangeof 8-15 mm as measured via echocardiography.
If we could not obtain a sufﬁcient mean atrial pressure despite maintaining intravenous volume,
norepinephrine and/or dobutamine was administered based on the patient s cardiac function. If theadministration speed of norepinephrine exceeded 0.1 µg/kg/h, we considered adding vasopressin tocontrol systemic peripheral vascular resistance.
Prolonged prone positioning for a minimum of three days
If a PaO2/FiO2 (P/F) ratio ≧150 could not be obtained even under maximum appropriate ventilatory
support, aggressive prone position therapy was introduced especially for patients with a computed
tomography (CT) ﬁnding of type H COVID-19 infection19). To obtain the maximum effect from thistreatment, the prone position was continued for ＞14 hours but ＜16 hours to avoid complications suchas pressure ulcers20,21). In the previous pandemic phase, we sometimes discussed about how manydays the prone position should be continued, and we ultimately decided to continue it for a minimumof three days if the patient was a candidate for this treatment.
Administration of extracorporeal membrane oxygenation (ECMO)
In patients in whom a P/F ratio of ＞100 could not be obtained even with the addition of prone
position therapy and there were no absolute contraindications in the patients, we started them onveno-venous ECMO as an additional treatment option.
Use of dexamethasone
In the previous pandemic phases, we generally used low-dose methylprednisolone at 1 mg/kg/day
if the patient met the diagnostic criteria for the acute phase of ARDS. But on the basis of current
reports22,23), we converted to the routine administration of dexamethasone at 6.6 mg/day for the ﬁrst
10 days for the patients requiring oxygen inhalation or mechanical ventilation.
Prophylactic administration of low molecular weight heparin
If there were no hemorrhagic complications on admission, we started low molecular weight
heparin from the first day of admission because of reports of a high incidence of complications ofhypercoagulopathy specific to COVID-1914-16). If the patients were complicated by disseminatedintravascular coagulopathy (DIC) as calculated by the acute DIC score during their clinical course24),
we converted them to the use of recombinant human soluble thrombomodulin and added
antithrombin Ⅲ if the value in the blood was ＜70%.
Periodic assessment of lung with computed tomography
In the previous phases, to avoid nonessential transport and supervenient infection, we avoided
performing periodic radiographic assessment of the lung by CT scan. Sometimes however, ﬁbroticchange of the lung in the late stage or pale ground-glass opacity of the dorsal lung was quite difﬁcult
to detect on portable chest x-ray images, so we decided to send the patient for a CT scan
approximately 7 days after admission, and strategic decision making was reconsidered on the basis of
the CT ﬁndings.
Nutrition management
During the previous pandemic phases, we continuous enteral nutrition support as much as
possible even if the patient was in the prone position. But sometimes the patients, and especially- 72 -

Outcome of COVID-19 with ARDS in Pandemic Phase 3

those in the prone position, vomited massively, and complications of aspiration pneumonia
exacerbated their respiratory condition. Hence, in the current study period, enteral nutrition for thepatients placed in prone positioning was administered only when they were in the supine position.
Furthermore, we strictly monitored gastric residual volume, and high caloric parenteral nutrition
was concurrently administered to these patients.
Statistical analysis
Statistical values are expressed as the median (interquartile range 25%-75%) or number (%).

Results
From October 2020 to March 2021, 70 patients were hospitalized with PCR-positive SARS-CoV-2
infection. We excluded 13 patients who did not require full management with mechanical ventilationand one patient who had been transferred in cardiopulmonary arrest on arrival. Finally, 56 patients
who met the criteria for ARDS based on the Berlin deﬁnition and were managed with mechanicalventilation were evaluated.
The previous medical histories of the patients at the time of admission are shown in Table 1. Their
median age was 73 (66-80) years old, and 38 patients (67.9%) were male. The number of days from
disease onset to admission to our hospital was 8 (6-11) days. The median Sequential Organ Failure
Assessment score at the time of intensive care unit (ICU) admission was calculated as 12 (12-14).
The results of the main blood tests and radiological types of COVID-19 infection obtained at thetime of ICU admission are shown in Table 2. The P/F ratio at the time of ICU admission was 170(132-222), and 18 (32.1%) patients had already been intubated at a previous hospital. Lactate
dehydrogenase on admission was 424 (368-496) IU/L, Krebs von der Lungen 6 was 466 (132-676)
U/mL, and C-reactive protein was 7.5 (4.1-14.4) mg/dL. Nine (16.1%) patients were classiﬁed by CT
scan to have Type L COVID-19 infection, which shows only ground-glass densities to be present, and47 (83.9%) patients had Type H infection, which shows a remarkable increase in lung weightespecially in the dorsal side of the bilateral lungs. The median value of P0.1 in the intubated patientson admission was 1.1 (0.6-1.7) cmH2O, and lung dynamic compliance was decreased to 31 (24-35) mL/
cmH2O.
The details of the clinical data are listed in Table 3. Although none of the patients had been inshock requiring vasopressors in the previous hospital, 49 (87.5%) of the patients required vasopressors
mainly due to the use of deep sedation concomitant with muscle relaxant drugs. Prone position
therapy, which was performed for approximately 16 (15.5-17) hours/day, was administered in 22 (39.3%)
patients. The concomitant complications observed during admission were ventilator-associatedpneumonia in 20 patient (35.7%), gastrointestinal bleeding requiring blood transfusion in two patients(3.6%), and mediastinal emphysema or pneumothorax in three patients (5.4%). Seven patients (12.5%)
had a systemic fungal infection for which they were administered anti-fungal drugs on the basis of
their β-D-glucan value, and Clostridioides difficile infection was present in ﬁve (8.9%) patients. One
patient had undergone cricothyrotomy because of endotracheal tube obstruction on the 12th day after
admission. A tracheostomy was subsequently performed in this patient, who was successfully weaned
from mechanical ventilation and whose cerebral performance category score was good.
ECMO therapy was indicated in two patients based on their P/F ratio on admission and Type L
radiographic findings. These two patients were managed by ECMO for 10 days and 14 days
respectively, and both patients were successfully extubated with no complications. Renal replacement- 73 -

Uchida et al
Table 1. Patient‌demographic data
N＝56
Sex, Male
Age, years
Transferred from other hospital
Onset to admission time (days)
Physiological data on arrival
GCS
Respiratory rate (breaths per min)Heart rate (beats per min)Systolic blood pressure (mm Hg)
Body temperature (℃)
Past medical history/Underlying disease
Current/Ex-smoker
Alcohol abuser
Hypertension
Diabetes
Hyperlipidemia
StrokeCardiac failure
COPD
Chronic kidney disease
AsthmaObesity
Malignant Disease
Gout
Psychological illness
Respiratory condition
ARDS
Mild
Moderate
SevereSOFA score on ICU admission

38 (67.9%)
73 (66-80)
52 (92.9%)
8 (6-11)15 (3-15)
25 (20-30)
88 (77-102)
148 (131-158)
36.4 (36.2-36.9)
20 (35.7%)
4 (7.1%)48 (85.7%)
29 (51.8%)
24 (42.8%)8 (14.3%)
5 (8.9%)5 (8.9%)7 (12.5%)
4 (7.1%)9 (16.1%)
14 (25.0%)
7 (12.5%)
3 (5.4%)56
20 (35.7%)
31 (55.4%)
5 (8.9%)12 (12-14)

Statistical data are presented as median (25%-75% interquartile range) or number.
GCS, Glasgow Coma Scale; COPD, chronic obstructive pulmonary disease; ARDS,
acute respiratory distress syndrome; SOFA, Sequential Organ Failure Assessment;
and ICU, intensive care unit.

therapy was administered in six (10.7%) patients due to their chronic kidney disease on dialysis andone patient (1.8%) due to acute kidney injury.
Recovery from ARDS and successful extubation was achieved in 30 patients (53.6%) over 8 (6-11)
days, and they were transferred to another hospital. Their dynamic lung compliance just before
extubation had improved to 62 (56-72) mL/cmH2O in the extubated patients. Tracheostomy was
performed in 24 (42.9%) patients, and five patients were successfully weaned from mechanicalventilatory support. The obtained cerebral performance category score of the patients at the point ofdisposition was 1 in thirty-eight patients (67.9%), 2 in eight (14.3%), 3 in one (1.8%), 4 in zero, and 5
in nine patients (16.1%). During this third pandemic study period, ﬁnal in-hospital mortality was
16.1% (9/56 patients).

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Outcome of COVID-19 with ARDS in Pandemic Phase 3
Table 2. Examination results at the time of ICU admission
N＝56
P/F ratio
P0.1
Dynamic lung compliance
PaCO2

170 (132-222)
1.1 (0.6-1.7)
31 (24-35)
42.4 (34.1-52.2)

Base excess−0.5 (−2.6-1.5)

pH
Lactate level (mmol/L)
WBC (/µL)
Plt (×104/µL)

7.397 (7.301-7.469)
1.2 (0.9-1.6)
8850 (5800-13000)
21.2 (15.0-27.0)
7.5 (4.1-14.4)
0.74 (0.59-1.14)
22.5 (17.5-33.5)
71 (33-173)
424 (368-496)
466 (132-676)
6.3 (5.9-6.8)

CRP (mg/dL)
Cr (mg/dL)
BUN (mg/dL)
CK (IU/L)LDH (IU/L)
KL-6 (U/mL)
HgbA1c (%)
T-Bil (mg/dL)
Fibrinogen (mg/dL)
FDP (µg/mL)
Type of COVID-19 infection classiﬁed by CT scan
Type LType H

0.5 (0.4-0.7)
531 (449-643)
6.8 (4.5-10.8)
9 (16.1%)
47 (83.9%)

Statistical data are presented as median (25%-75% interquartile range). ICU,
intensive care unit; P/F, PaO2/FiO2; WBC, white blood cell count; Plt, platelet count;
CRP, C-reactive protein; Cr, creatinine; BUN, blood urea nitrogen; CK, creatine
kinase; IU/L, international unit; LDH, lactate dehydrogenase; KL-6, Krebs von derLungen 6; HgbA1c, hemoglobin A1c; T-Bil, total bilirubin; FDP, ﬁbrinogen degradation
products; and CT, computed tomography.

Discussion
Ever since the ﬁrst pandemic of COVID-19 occurred in 201925), treatment strategies for COVID-19
and the related ARDS have been documented globally and updated as clinical recommendations23).
Currently, however, we still lack radical antiviral treatment agents to treat this human crisis25,26). The
respiratory management of ARDS has been discussed globally for some time4,17,27). Generally, highpositive end-expiratory pressure (PEEP) and low tidal volume to prevent shearing injury of thealveoli are considered important in the management to rest the lungs, but methods to control andlimit spontaneous inspiratory effort have not been established yet. To control these self-inspiratory
efforts, we use muscle relaxant drugs as the treatment option for ARDS patients. However, theadministration of muscle relaxant drugs to control self-inspiratory efforts and oxygen consumption ofpatients suffering ARDS remains controversial 10,28). Papazian et al 10) previously reported theimportance of muscle relaxant drugs for patients with ARDS. They used muscle relaxant drugs forabout 48 hours for their patients with a P/F ratio of under 150 and reported a 32% decrease in 90-day
mortality and decreases in the number of ventilator days and intensive care unit admission days. In
contrast, Putensen et al29) reported that maintaining spontaneous breathing and adopting airway
pressure release ventilation obtained good outcomes as well. Our previous management strategy,
which was similar to this strategy of maintaining spontaneous breathing, did not result in excellent- 75 -

Uchida et al
Table 3. Clinical‌
courses
N＝56
Successful extubation
Length of ventilator support from admission, days
Length of stay in ICU, days
Dynamic lung compliance before extubation
Tracheostomy
Length of ventilator support from admission, days
Length of stay in ICU, days
Dynamic lung compliance before tracheostomy
Required prone positioning
Length of prone positioning days (days)
Length of prone positioning hours per day (hours)
Required blood transfusion
Steroid use
Muscle relaxant use
Vasopressor use
CRRT
ECMO
Tracheostomy/Cricothyrotomy
Concomitant comorbidities during admission
Pneumothorax
Mediastinal emphysema
Ventilator associated pneumonia
Endotracheal re-intubation
Acute kidney injury requiring CRRT
Gastrointestinal bleeding
Deep venous thrombosis
Systemic fungal infection
Mild pressure sore (prone-positioned patient)
Clostridioides difficile infection
CPC grade obtained on disposition
Ⅰ
Ⅱ
Ⅲ
Ⅳ
Ⅴ
In-hospital mortality

30 (53.6%)
8 (6-11)10 (6.5-13.5)
62 (56-72)
24 (42.9%)
18 (16-21)
18.5 (16-22)
32 (26-34)
22 (39.3%)
3 (3-5)16 (15.5-17)
8 (14.3%)
56 (100%)
49 (87.5%)
49 (87.5%)
7 (12.5%)
2 (3.6%)22 (39.3%)/1 (1.8%)
2 (3.6%)
1 (1.8%)20 (35.7%)
1 (1.8%)1 (1.8%)2 (3.6%)
1 (1.8%)7 (12.5%)
2 (3.6%)5 (8.9%)38 (67.9%)
8 (14.3%)
1 (1.8%)0
9 (16.1%)
9 (16.1%)

Statistical data are presented as median (25%-75% interquartile range) or number. ICU,
intensive care unit; CRRT, continuous renal replacement therapy; ECMO, extracorporeal
membrane oxygenation; and CPC, Cerebral Performance Category.

outcomes for ARDS following COVID-196). We consider that one reason for this outcome arose fromnot preventing P-SILI. Self-inﬂicted lung injury is also being re-emphasized in the management of
COVID-19 because the huge inspiratory efforts to correct hypoxia cause additional shearing injury of
the alveoli4,16). Administration of deep sedation and concomitant use of muscle relaxant drugs are
efficient to avoid P-SILI, but the difficulty in preferentially addressing this problem in COVID
patients is that we cannot assess complications of thromboembolic events such as cerebral infarction
during the administration of muscle relaxant. By administering anticoagulant drugs from the ﬁrst

- 76 -

Outcome of COVID-19 with ARDS in Pandemic Phase 3days of admission and continuous daily checking of the values of coagulation factors such as
ﬁbrinogen degradation products (FDP), we could prevent thromboembolic events during this period.
Furthermore, the importance of monitoring airway pressure including transpulmonary pressure iscurrently being emphasized, but there are still no strong recommendations for the respiratory
management of COVID-19-related ARDS. From our experience in the previous pandemic phases,
during which we struggled with how to manage spontaneous inspiratory efforts of the intubatedpatients, we start monitoring P0.1, which allows us to estimate inspiratory effort of the patients eventhough respiratory muscle weakness may be present30-32). As the value of P0.1 at the time of ICU
admission was scored under deep sedation with muscle relaxant drugs, hence the value wasconsidered to have been well regulated. Similarly, during the administration of muscle relaxant
drugs, P0.1 is well controlled under 5 cmH2O, and this is one of the important reasons we could
obtained good outcomes in the present study period. Under use of muscle relaxant drugs, therespiratory drive of all of our patients was well controlled by PRVC ventilation, and the intratrachealpressure was also controlled under 30 mmH2O, regardless of whether the patients had a massive type
L or H radiographic appearance. And also, after muscle relaxant drugs being terminated, theadministration of morphine sulfate seemed effective to control excess spontaneous respirations andthe respiration of the patients was well synchronized to the ventilator support compared to fentanyl.
As additional treatment, especially for the patients with type H appearance, we considered thestrategies combining prone positioning and muscle relaxant treatment with PRVC ventilation to be
efﬁcient. However, in the patients with type L appearance, the prone position does not adequately
correct V/Q mismatch, so we aggressively applied veno-venous (V-V) ECMO if the patient had not
obtained improvement under best ventilatory support. We applied V-V ECMO in two patients during
the present study period, and both were successfully weaned from ECMO, extubated, and transferred
to a rehabilitation hospital.
The use of remdesivir as an anti-viral drug, which we used continuously during the study period,
is controversial, and WHO also reported that there were no strong recommendations for using thisdrug23). However, as there are currently no established anti-viral drugs against COVID-19, we willcontinue to use remdesivir for all patients except those with renal failure.
Another key modification of our strategy against ARDS following COVID-19 was in convertingfrom the previous use of low-dose methylprednisolone to the use of dexamethasone. Althoughdexamethasone appeared to be efﬁcient in the treatment of ARDS during the present study period aswell, because of its long-term use of approximately 10 days, it caused some adverse side effects,
especially in terms of infection control. We will need to assess the efﬁcacy of dexamethasone use inupcoming multi-institutional randomized control trials.
Lastly, since no complication such as cerebral hemorrhage or cerebral infarction had been detectedduring their admission, the obtained CPC score of 2 and 3 were presumed because of sedative coma
but had to be transferred to rehabilitation hospital before their awakening.
Although the present descriptive statistical outcomes are reported from a small number ofpatients at a single institution, our modiﬁed systematic stepwise intensive care strategy for treating
ARDS secondary to COVID-19 in the third pandemic period in Japan improved patient outcomescompared to those in the previous two pandemic phases.
We conclude that our modiﬁed systematic stepwise strategy of intensive care for treating ARDS
secondary to COVID-19 used in the third phase of the pandemic in Japan achieved improved- 77 -

Uchida et al

outcomes compared to the high mortality rates seen around the world including elsewhere in Japan.
After we had updated our treatment strategy on the basis of global evidence, several important
tactical changes including in respiratory management had been made after the first and second
domestic pandemic periods. Hence, we realize that numerous co-variants need to be analyzed todetermine which factors significantly impacted the current descriptive statistical outcomes.
Furthermore, as the number of patients who can be analyzed with propensity-matched analysis iscurrently insufﬁcient, as the next step, we deﬁnitely need to evaluate which co-factors are the mostefficient in improving our short-term outcomes of ARDS following COVID-19. We are currently
proceeding with a multi-institutional randomized control trial to reassess our outcomes on the basisof the present study.
Acknowledgements
All authors have no COI to declare regarding the present study.
Written informed consent for this report was obtained from the patients or their family members.
We sincerely dedicate this paper to all essential health workers who have fought against
COVID-19 not only directly but also secondarily in Osaka City University Hospital. The excellent
results are due to the tremendous cooperation and teamwork of all of the staff involved in such tasks
as preventing nosocomial infections, redistributing staff, and temporarily limiting elective operations.
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Osaka City Med. J. Vol. 67, 81-90, 2021

An Analysis of Compensatory Trunk Movements in Shoulder
Joint Movements: Application to Healthy Individuals andPatients after Shoulder Joint Surgery
TAMOTSU NAKATSUCHI1), MITSUHIKO IKEBUCHI2,4), TAKAHIRO NISHINOHARA4),SHIGEYOSHI NAKAJIMA3), and HIROAKI NAKAMURA4)
Tsuji-GEKA Rehabilitation Hospital1);
Department of Rehabilitation medicine2), Osaka City University Hospital;
Department of Electric Information System3),
Osaka City University Graduate School of Engineering; andDepartment of Orthopedic Surgery4), Osaka City University Graduate School of Medicine

Abstract
Background
Evaluating upper limb function, particularly shoulder joint kinematics, in activities of daily living
is important during rehabilitation. However, an extensive search did not identify any studies
investigating the effect of compensatory trunk movements on shoulder joint kinetics using radiographs.
Thus, we aimed to compare compensatory trunk movements during shoulder joint kinematics
between healthy individuals and patients who had undergone reverse shoulder arthroplasty.
Methods
We included 10 healthy adult shoulders (healthy group) and four shoulders that had undergone
reverse shoulder arthroplasty (impaired group). After the attachment of surface markers over the
manubrium sterni and spinous process of the third thoracic vertebra to evaluate compensatory trunk
movements, participants performed voluntary abduction of the shoulder under ﬂuoroscopy, and thetrunk compensation angle was measured on radiographs.
Results
After shoulder abduction of 90°, the healthy group performed compensatory trunk retroﬂexion, as
indicated by the kinematics of the shoulder joint. In the impaired group, at the maximum shoulder
abduction position there was lateral ﬂexion of the trunk to the side contralateral to the evaluatedshoulder joint and rotation to the side ipsilateral to the evaluated shoulder joint. These findings
suggest that compensatory trunk movements occurred in the impaired group in response to reduced
shoulder function. Therefore, evaluating compensatory trunk movements over time, in addition to
performing range-of-motion and muscle strengthening exercises for improving shoulder joint function,

Received March 11, 2021; accepted August 27, 2021.
Correspondence to: Tamotsu Nakatsuchi, MD, phD.
Tsuji-GEKA Rehabilitation Hospital,
3-24 Ikutamamaemachi, Tennouji-Ku, Osaka 543-0072, Japan
Tel: +81-6-6771-0681; Fax: +81-6-6773-8647
E-mail: nakatsuchi@kankikai.com- 81 -

Nakatsuchi et alis important in patients undergoing reverse shoulder arthroplasty.
Conclusions
Simultaneous evaluation of the shoulder joint and compensatory trunk movements may provide
rehabilitation programs to improve activities of daily living.
Key Words: ‌Compensatory trunk movements; Joint kinetics;
Reverse shoulder arthroplasty; Rehabilitation program

Introduction
In activities of daily living (ADL), upper limb function is important, and the function of theshoulder joint, which is the joint at the base of the upper limb, is particularly important. However,since the movement is complicated, various methods have been used for kinematic analyses toevaluate the function and assess the effects of therapy. Recently, with advances in measuring
instruments, various analyses using radiographs have been carried out, and methods of 2D-3D
registration that match 3D models, such as computed tomography (CT) and magnetic resonance (MR)images, with 2D models, such as radiographs, have been sporadically observed1).
The movements of the shoulder joint are carried out jointly via the anatomic joints (theglenohumeral, acromioclavicular, and sternoclavicular joints) and functional joints (thescapulothoracic and second shoulder joints, as well as the trunk, thorax, and lower limbs). If
glenohumeral joint mobility is reduced, the scapulothoracic joint compensates to allow mobility; if
scapular mobility is reduced, compensatory movements such as anteroposterior flexion, lateral
ﬂexion, and rotation of the trunk may occur. However, in our literature search, there were no reports
on shoulder joint kinematics that described such compensatory trunk movements during radiographic
evaluation, and analyses are thought to have been performed with the implicit understanding thatthe posture of participants was constant2).
In order to accurately perform shoulder joint kinematics analyses, gaining an understanding of
the compensatory trunk movements and performing more detailed kinematic analyses wereconsidered necessary. Therefore, in this study, the effects of compensatory trunk movements onshoulder abduction movements were investigated.
We aimed to compare compensatory trunk movements during shoulder joint kinematics between
healthy individuals and patients who had undergone reverse shoulder arthroplasty (RSA).

Methods
Ten shoulders from 5 healthy adults with no history of shoulder disease (the healthy group) and
four shoulders from four patients who had undergone shoulder arthroplasty (the impaired group)
were included in this study. All participants in the healthy group were men, with a mean age of 38.2
±11.7 years, and both shoulder joints were evaluated. All participants in the impaired group were

women, with a mean age of 75.5±5.6 years, and only the affected shoulders were evaluated. The
primary disease in the impaired group was osteoarthritis of the shoulder with rotator cuff tears, andall patients had undergone RSA.
Compensatory trunk movements were measured as the angles of inclination of the thoracic systemof coordinates relative to the X-ray system of coordinates, based on frontal chest radiographs in thestanding position including the humerus, shoulder joint, scapula, and sternum. The X-ray system of
coordinates was deﬁned using the X-ray source as the origin, the perpendicular line from the X-ray- 82 -An Analysis of Compensatory Trunk Movements in Shoulder Joint Movements

source to the shooting table as the anterior-posterior axis, the vertical line orthogonal to this axis andpassing through the origin as the vertical axis, and the axis orthogonal to the anterior-posterior axis
and vertical axis and passing through the origin as the horizontal axis.
In the upright position, the upper margin of the sternum is known to be at the same height as the
2nd to 3rd thoracic vertebrae. Using this, the origin was deﬁned as the suprasternal notch Incisura
Jugularis; the axis passing through the origin and the spinous process of the 3rd thoracic vertebra
was the anterior-posterior axis of the thorax, the line connecting the left and right proximal clavicles
that is parallel and orthogonal to the anterior-posterior axis and passes through the origin was thehorizontal axis, and the axis orthogonal to the anterior-posterior and horizontal axes and passing
through the origin was the vertical axis.
The inclination was deﬁned using the angle between the anteroposterior axes of the X-ray and thethoracic systems of coordinates in the horizontal plane as the angle of rotation of the thorax, theangle between the horizontal axes of the X-ray and thoracic systems of coordinates in the frontal
plane as the lateral ﬂexion angle of the thorax, and the angle between the anteroposterior axes of the
X-ray and thoracic systems of coordinates in the sagittal plane as the anteroposterior ﬂexion angle ofthe thorax.
Plain radiographs were taken after a cruciform marker (sternum marker) was attached to thesuprasternal notch and a ring-shaped marker (spinous process marker) was attached to the spinous
process of the 3rd thoracic vertebra. Sternum markers were applied such that the transverse bar
passed through the suprasternal notch and was parallel to the line connecting the right and left
proximal clavicle ends, and the longitudinal bar was orthogonal to the transverse bar and bisected
the sternum. The spinous process markers were applied such that the center of the ring coincidedwith the spinous process of the 3rd thoracic vertebra (Fig. 1).
With these markers attached, the participants underwent frontal plain radiography with the chestin the upright position. The distance between the source and the imaging plate was set to 100 cm,
and the participant's scapula and occipital bone were set to be in contact with the imaging plate. In
instances where contact was not feasible due to a hunched back or other reasons, the participant was
conﬁrmed to be in an upright position, and the participant was positioned such that the top of the
kyphosis was in contact with the imaging plate. If it was still unstable, the participant was seated ina chair and the scapula and occipital region were brought into contact with the imaging plate.
To reproduce the compensatory trunk movements, participants were instructed to performvoluntary abduction movements in increments of 30°from the dropped shoulder position (abduction0°) and imaging was performed. The maximum abduction angle was set at 180°of abduction and, if
abduction of 180°was difﬁcult, the maximum abduction angle which participants could achieve wasset as the maximum voluntary abduction angle. The range of motion of voluntary shoulder abduction
was measured using a goniometer in accordance with the range of motion and measurement methods
defined by the Japanese Orthopaedic Association and the Japanese Association of Rehabilitation
Medicine.
Chest thickness (the distance between the sternum and spinous process markers) and the distance
between the imaging plate and the spinous process marker in plain radiographs were measured asnecessary parameters at the time of imaging. At the measurement, we used the outside caliper formeasuring pelvis, and the inside caliper for measuring the inner diameter of pipes, etc.
In terms of ethical considerations, full informed consent was obtained from all participants.

- 83 -

Nakatsuchi et al

Figure 1. A cruciform marker (Right: sternum marker) was attached to the suprasternal notch and a ring-shaped
marker (Left: spinous process marker) was attached to the spinous process of the 3rd thoracic vertebra.

Approval to conduct the research was also obtained from the Institutional Review Board (Approval
No. 36).
The following calculation method was devised for evaluating compensatory trunk movements atangles.
X1, Y1, and Z1 were set as the coordinates of the spinous process marker in the X-ray system of
coordinates, while X2, Y2, and Z2 were set as the coordinates of the sternum marker; l1 is the distance
between the imaging plate and the spinous process marker, l2 is the distance between the imaging
plate and the sternum marker, and l3 is the chest thickness (the distance between the sternum andspinous process markers). L was the distance from the X-ray source to the shooting table, and it wasmeasured to be 1000 mm. On the plain radiographs, the center of the screen was the intersection
between the plane containing the imaging plate (IP) and the perpendicular line from the X-ray
source, that is, the anterior-posterior axis in the X-ray system of coordinates. In the plainradiographs, the horizontal distance from the center of the screen to the center of the spinous process
marker was denoted as x1, while the vertical distance was denoted as y1; the horizontal distance fromthe center of the film to the center of the sternum marker (the intersection of the transverse andlongitudinal bars) was denoted as x2, and the vertical distance was denoted as y2 (Fig. 2).
Based on the aforementioned parameters, the spinous process marker coordinates (X1, Y1, Z1) wereexpressed as follows:- 84 -An Analysis of Compensatory Trunk Movements in Shoulder Joint Movements

Figure 2. In the plain radiographs, the horizontal distance from the center of the screen to the center of the spinous
process marker was denoted as x1, while the vertical distance was denoted as y1; the horizontal distance from thecenter of the ﬁlm to the center of the sternum marker was denoted as x2, and the vertical distance was denoted as y2.

Spinous process marker coordinates(X1, Y1, Z1)＝(x1 • (L−l1)/L, y1 • (L−l1)/L, L−l1)(Formula 1)

Similarly, the coordinates of the sternum markers (X2, Y2, Z2) were expressed as follows:
Sternum marker coordinates(X2, Y2, Z2)＝(x2 • (L−l2)/L, y2 • (L−l2)/L, L−l2)(Formula 2)

The chest thickness, that is, the distance between the sternum and spinous process markers (l3),was calculated as
l32＝(X1−X2)2＋(Y1−Y2)2＋(Z1−Z2)2
X1, X2, Y1, Y2, Z1, and Z2 were substituted from Formula 1 and Formula 2. This Formula was thequadratic equation where l2 represents an unknown.
A•l22＋B•l2＋C＝0
A＝(x2/L)2＋(y2/L)2＋1
B＝−2•{(x1/L)(x2/L)(L−l1)＋(y1/L)(y2/L)(L−l1)＋(L−l1)}
C＝{x1/L•(L−l1)}2＋{y1/L•(L−l1)}2＋(L−l1)2−l32(Formula 3)

L, l1, l3, x1, y1, x2, and y2 were measured values. l2 was calculated from Formula 3 and substituted
into Formula 2 to obtain the sternum marker coordinates (X2, Y2, Z2) (Fig. 3).
Next, the angles of thoracic rotation, anteroposterior ﬂexion, and lateral ﬂexion were calculated.
The angle of rotation of the thorax (the angle in the horizontal plane between the anteroposterioraxes of the X-ray and thoracic systems of coordinates) was denoted by α; β denoted the anteroposterior- 85 -

Nakatsuchi et al

Figure 3. L, l1, l3, x1, y1, x2, and y2 were measured values. l2 was calculated from Formula 3 and substituted into
Formula 2 to obtain the sternum marker coordinates (X2, Y2, Z2).

Figure 4. Angles α and β were calculated from formula 4 using the inverse tangent function.

flexion angle of the thorax (the angle between the anteroposterior axes of the X-ray and thoracic
systems of coordinates in the sagittal plane), and γ denoted the lateral ﬂexion angle of the thorax (theangle between the horizontal axes of the X-ray and thoracic systems of coordinates in the frontal
plane). The angle α was the angle between the projection of the line connecting the sternum andspinous process markers on the horizontal plane and the line connecting the origin of the X-ray
system of coordinates and the center of the screen. The angle β was the angle between the projectionof the line connecting the sternum and spinous process markers on the sagittal plane and the line
connecting the origin of the X-ray system of coordinates and the center of the screen. The
relationship between the coordinates of each marker and the angles α and β was expressed as follows(Fig. 4).
Tanα＝(X2−X1)/|Z2−Z1|
Tanβ＝(Y2−Y1)/|Z2−Z1|(Formula 4)- 86 -An Analysis of Compensatory Trunk Movements in Shoulder Joint Movements
Table 1. ‌Trunk movements due to abduction of shoulder
Abduction of
Shoulder(degree)

Sagittal plane

Frontal plane

Holizontal plane

healthy group impaired group healthy group impaired group healthy group impaired group3.2±1.9
3.5±2.1

2.6±2.0

0.7±0.8

1.5±0.9

3.0±2.4

3.6±1.030

3.5±2.6

1.0±1.1

1.8±1.92.8±2.4

3.9±2.460

3.1±1.890120

3.6±2.0
6.0±3.8

3.0±2.1
3.0±2.5

1.7±1.4
1.7±1.4

3.5±4.1
5.0±2.4

2.3±2.5
2.3±2.4

4.3±2.2
8.8±3.3150

8.6±3.912.2±4.40180

2.8±2.1

2.8±2.7

1.8±1.2

2.3±2.3

1.3±1.7

4.0±2.6＊(degree, Mean±SD, ＊p＜0.05)
In the results of the healthy group and the impaired group, the difference in the trunk rotation angle at 90 degrees
of shoulder abduction was statistically signiﬁcant (p＜0.05), but the others were not signiﬁcant.

Angles α and β were calculated from formula 4 using the inverse tangent function.
The angle change (γ) in the frontal plane was measured as the angular difference between thehorizontal line on the screen and the transverse axis of the sternum marker.
Statistical analysis software R was used to compare the healthy group and the impaired group,and the Mann-Whitney U test was used, and the signiﬁcance level was set to p＜0.05.

Results
Trunk movements due to abduction of shoulder are shown in Table 1.
Voluntary shoulder abduction up to 180°was observed in the healthy group, while in the impaired
group, the maximum voluntary abduction angle was 90°in 3 patients and 75°in 1 patient.
The angle of anteroposterior trunk flexion in the healthy group remained ≦5°up to 90°ofshoulder abduction, but increased beyond 90°of shoulder abduction. No signiﬁcant changes in thetrunk anteroposterior ﬂexion angle were observed regardless of the shoulder abduction angle in the
impaired group. The angle of lateral trunk ﬂexion remained ≦5°in both the healthy and impaired
groups; however, in the impaired group, the greater the angle of shoulder abduction, the greater thedifference from the healthy group. The trunk rotation angle did not change significantly in thehealthy group regardless of the shoulder abduction angle; however, the trunk rotation tended toincrease with shoulder joint abduction in the impaired group.
In the results of the healthy group and the impaired group, the difference in the trunk rotation
angle at 90 degrees of shoulder abduction was statistically signiﬁcant (p＜0.05), but the others were
not signiﬁcant.

Discussion
Upper limb function is involved in almost all activities and is important in ADL. Many shoulder
movements require an adequate range of motion, and shoulder abduction of approximately 100°is
necessary for ADL such as washing the body and combing hair. Thus, it is clinically important torestore shoulder abduction ＞100°.
The shoulder joint is moved using combined efforts from the anatomic glenohumeral joint
consisting of the humerus and scapula and a functional scapulothoracic joint consisting of the scapula- 87 -

Nakatsuchi et al

and thorax. If the shoulder joint is damaged, such as with rotator cuff injuries or adhesive capsulitis,the movement of the scapula associated with the movement of the upper limb is said to be different
from that in healthy individuals7). If shoulder joint mobility is reduced, the scapula compensates and,if this is insufﬁcient, compensatory trunk movements may occur. In addition, from the perspective of
rehabilitation medicine, it is necessary to secure the maximum range of motion of each joint in orderto enable ADL; however, if there are limitations, compensatory movements should also be utilized.
On the other hand, excessive compensatory movements may reduce the function of the original joint.
Therefore, it is clinically important to analyze and evaluate the kinematics of compensatory
movements.
To date, various kinematic analyses have been developed for the objective evaluation of shoulder
joint movement. In general, the analysis is performed using a goniometer and a ruler onradiographs3,4); however, because the analysis is performed using projection images, three-dimensional
analyses are difﬁcult. To solve this issue, an analysis using radiographs that were simultaneously
taken from the front and a 90°angle has been reported; however, a special shooting table was
required 5). Kinematics analyses using CT/MR images have also been reported; however, radiation
exposure and limitation of the position of the limb being imaged pose issues.
Recently, there have been several reports of kinematics analyses using 2D-3D registration. This isa method to estimate the position and posture based on the moving distance of the coordinates by
setting spatial coordinates in 3D models obtained from CT or MR imaging and matching these with
2D radiographs1,2), and this enables measurement, including movements over time, in a relatively
noninvasive manner.
However, in all reports, the patient position during radiography was not strictly deﬁned, and theanalyses were performed assuming that the posture of participants during imaging was constant.
Therefore, in the present study, the effects of compensatory trunk movements on shoulder joint
kinematics during radiography were evaluated.
In the healthy group, trunk retroﬂexion ＞5°was observed after shoulder abduction of at least 120°.
In general, extension of the vertebral column, that is, retroﬂexion of the trunk, is required in the latephase of shoulder abduction, and the mechanism is considered to be the contraction of the lower
trapezius ﬁbers, which are involved in the retroﬂexion of the trunk, moving the scapula downward,
leading to the extension of the vertebral column and retroﬂexion of the trunk. The trunk retroﬂexion
in the healthy group in this study was considered to represent the aforementioned physiologicalmovements.
In the impaired group, lateral flexion of the trunk to the contralateral side and rotation of thetrunk to the ipsilateral side exceeded 5°in the ﬁnal range of shoulder abduction. In healthy shoulder
joints, the scapular glenoid fossa is smaller than the humeral head, resulting in greater mobility;
however, the ﬁt is shallow and stability is poor. The humeral head is covered by four rotator cuff
muscles and stabilized by pressing against the glenoid fossa. In this manner, the deltoid muscle, themain movement muscle, works effectively in coordination with the rotator cuff muscles, causing the
glenohumeral joint to abduct. RSA is indicated for surgery in patients with rotator cuff teararthropathy and wide ruptures of the rotator cuff that cannot be repaired temporarily in the elderlypresenting with pseudoparalysis where it is difficult for the patients to raise their arm bythemselves 6,7). Therefore, in the impaired group, the deltoid muscle did not work effectively andmobility decreased due to instability of the shoulder joint caused by the decreased function of the- 88 -An Analysis of Compensatory Trunk Movements in Shoulder Joint Movements

rotator cuff muscles. Walker et al reported8,9) that in rotator cuff tear, shoulders with reduced rotator
cuff function, and post-RSA shoulders, the shoulder joint mobility decreases, and upward rotation of
the scapula increases during shoulder abduction. Trunk rotation in the impaired group is thought tocompensate for the upward rotation of the scapula due to the deltoid muscles not working effectively,
which in turn is caused by the decreased function of the rotator cuff muscles, resulting in decreased
shoulder joint mobility. However, securing sufﬁcient mobility is insufﬁcient, and additional lateral
bending of the trunk toward the measured side and contralateral side should be considered tocompensate for shoulder abduction.
In addition, humeral external rotation is required for shoulder abduction in the frontal plane inhealthy shoulders since the humeral head passes through the subacromial space at 90°of shoulder
abduction, while humeral external rotation is not required for shoulder abduction in the scapularplane (horizontal adduction of approximately 30°from the frontal plane), and abduction is easier toperform than that in the frontal plane. In the impaired group, the function of the rotator cuff muscles
was reduced, and abduction in the scapular plane, which is more prone to abduction, was considered
to be attempted during shoulder abduction. However, since shoulder abduction in the frontal plane
was indicated at the time of radiographic evaluation, participants were considered to be performing
apparent shoulder abduction in the frontal plane by performing compensatory movements of rotating
the trunk ipsilateral to the measured side and aligning the scapular plane with the horizontal plane.
In the healthy group, physiological movements of trunk retroﬂexion were observed after shoulder
abduction of at least 120°, and in the impaired group, compensatory trunk movements were observedin the final range of shoulder abduction. When evaluating the shoulder joint on radiographs,
attention must be paid to the physiological movement of trunk retroﬂexion in the sagittal plane evenin healthy individuals. In addition, attention must also be paid to compensatory trunk movements
such as trunk lateral ﬂexion and rotation in the frontal and horizontal planes in patients after RSA
surgery with reduced rotator cuff function.
Limitations of this study include the small sample size and healthy individuals being younger
than the impaired group. Since thoracic vertebral kyphosis and shoulder girdle function change andscapular and humeral kinetics differ in the young and the elderly10,11), there is a need to perform
evaluations in groups with wider age ranges. Furthermore, there is a need to clarify the relationshipwith compensatory trunk movements in more detail by conducting studies that include assessmentsof muscle strength and the range of motion of other joints.
Simultaneous evaluation of the shoulder joint and compensatory trunk movements may provide
rehabilitation programs to improve activities of daily living. Unrestricted free shoulder abduction
may result in even greater trunk compensatory movements, and when performing clinicalrehabilitation, it is necessary to pay attention to trunk movement and ﬂexibility in addition to the
glenohumeral joint and scapulothoracic joint. In the future, we hope to evaluate how compensatory
trunk movements affect actual ADL and to develop more effective rehabilitation programs.
Acknowledgements
All authors have no COI to declare regarding the present study.
References
1. Yamazaki N, Watanabe T, Sato Y, et al. CAD based on 2D-3D registration and visualization. Medical Imaging- 89 -

Nakatsuchi et al
Technology 2006;24:94-100.
2. Mahfouz MR, Hoff WA, Komistek RD, et al. A robust method for registration of three-dimensional knee
implant models to two-dimensional ﬂuoroscopy images. IEEE Trans Med Imaging 2003;22:1561-1574.
3. Inman VT, Saunders JB, Abbott LC. Observations of the function of the shoulder joint. 1994. Clin Orthop
Relat Res 1996;(330):3-12.
4. Freedman L, Munro RR. Abduction of the arm in the scapular plane: scapular and glenohumeral movements.
A roentgenographic study. J Bone J Surg Am 1966;48:1503-1510.
5. Bey MJ, Zauel R, Brock SK, et al. Validation of a new model-based tracking technique for measuring threedimensional, in vivo glenohumeral joint kinematics. J Biomech Eng 2006;128:604-609.
6. Boudreau S, Boudreau ED, Higgins LD, et al. Rehabilitation following reverse total shoulder arthroplasty. J
Orthop Sports Phys Ther 2007;37:734-743.
7. Hatzidakis AM, Norris TR, Boileau P. Reverse shoulder arthroplasty indications, technique, and results.
Techniques in Shoulder and Elbow Surgery 2005;6:135-149.
8. Mell AG, LaScalza S, Guffey P, et al. Effect of rotator cuff pathology on shoulder rhythm. J Shoulder Elbow
Surg 2005;14:58S-64S.
9. Walker D, Matsuki K, Struk AM, et al. Scapulohumeral rhythm in shoulders with reverse shoulder
arthroplasty. J Shoulder Elbow Surg 2015;24:1129-1134.
10. Dayanidhi S, Orlin M, Kozin S, et al. Scapular kinematics during humeral elevation in adults and children.
Clin Biomech (Bristol, Avon) 2005;20:600-606.
11. Endo K, Yukata K, Yasui N. Influence of age on scapulo-thoracic orientation. Clin Biomech (Bristol, Avon)
2004;19:1009-1013.

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Osaka City Med. J. Vol. 67, 91-96, 2021

Orbital Venous Malformation with Obscure Clinical Symptoms
Diagnosed by Contrast-enhanced Magnetic Resonance Imaging
in a Different Body Position
AKIKA KYO1), YUSAKU YOSHIDA2), MIZUKI TAGAMI1), MASAO HAMURO3), and SHIGERU HONDA1)
Department of Ophthalmology and Visual Sciences1),
Osaka City University Graduate School of Medicine; andDepartments of Ophthalmology2) and Radiology3), Izumiotsu Municipal Hospital

Abstract

Orbital venous malformations are the most common type of orbital vascular anomaly. The main
initial complaints are presence of a mass, proptosis, globe displacement, or hemorrhage. Since thesubjective symptoms of this condition usually become noticeable only after the mass has increased insize, small malformations often remain undetected. Imaging modalities such as computed
tomography, magnetic resonance imaging, magnetic resonance angiography, and endovascular
contrast are commonly used for diagnosis, but are not always successful.
In the present manuscript, we report a case of a 54-year-old woman who presented with acute,severe eye pain and swelling. Only slight subcutaneous hemorrhage was present, and no
exophthalmos or eyelid swelling was identiﬁed. Precontrast computed tomography and precontrast
magnetic resonance imaging were unable to provide a definitive diagnosis. Notably, the patientcomplained that symptoms worsened when she changed body positions. Bearing this in mind, orbital
venous malformation was eventually diagnosed by changing her body position during contrastenhanced magnetic resonance imaging. Cases of orbital venous malformations without obvious
clinical symptoms may exist and magnetic resonance imaging with different body positions could
offer a more deﬁnitive diagnosis.
Key Words: ‌Imaging; Orbit; Vascular malformation

Introduction
Orbital venous malformation (OVM) is the most common type of venous malformation in the orbit.
The main symptoms of OVMs are presence of a mass, proptosis, globe displacement, edema, andhemorrhage around the eyelids, and deep orbital pain.
In addition, distensible OVM demonstrates as an initial small nidus with filling in the preValsalva arterial phase, and progressive filling and expansion in the subsequent Valsalva venous
phase. However, such cases usually show obvious clinical symptoms such as visual loss, proptosis, orReceived May 10, 2021; accepted August 27, 2021.
Correspondence to: Akika Kyo, MD.
Department of Ophthalmology and Visual Sciences, Osaka City University Graduate School of Medicine,
1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan
Tel: +81-6-6645-3867; Fax: +81-6-6645-3873
E-mail: m2071526@med.osaka-cu.ac.jp- 91 -

Kyo et alspontaneous hemorrhage. As subjective symptoms usually become noticeable when the mass
increases in size, small malformations often pass undetected or cause few symptoms.
We report herein a case of OVM that caused few clinical symptoms and could not be diagnosed on
precontrast computed tomography (CT) or precontrast magnetic resonance imaging (MRI), but was
eventually diagnosed by contrast-enhanced MRI with the patient in a different body position.

Case Report
A 54-year-old woman presented at the emergency room of another hospital with left eyelid pain,
left eyelid swelling and nausea. She had previously noticed discomfort around the left eye when lying
face down. Results of cranial CT were unremarkable, and as blood tests revealed a slightly elevatedwhite blood cell count, a cephem antibiotic was prescribed. The patient was examined in our
department the following day for further ophthalmological investigations. Best-corrected visualacuity was 0.9 on the right and 1.0 on the left, with no other intraocular abnormalities. The bilateraleye movements were also normal, and no exophthalmos was identified. Mild subcutaneous
hemorrhage of the left eyelid was present, but left eyelid swelling had improved (Fig. 1). No otherobjective signs were present. Because the symptoms had improved with antibiotic treatment, orbital
cellulitis was initially suspected. MRI revealed a lesion in the extraconal medial rectus oculi muscle
and ethmoid sinus wall within the left orbit, appearing hypointense on T1-weighted image andhyperintense on T2-weighted and short T1 inversion recovery (STIR) image (Figs. 2A-2C). Sinusitis
was also present in the ethmoid sinus (Fig. 2D). These observations were believed to represent
sinusitis-induced orbital cellulitis, and antibiotic treatment was continued.
Two weeks later, the patient complained of left recurrent eye pain that was aggravated whenlooking downwards. Precontrast MRI and magnetic resonance angiography (MRA) carried out thatday showed that the lesion had increased somewhat in size since the previous scans (Fig. 3). The
lesion appeared lobulated with an ill-defined edge, but no abnormal vessels suggestive ofarteriovenous malformation or arteriovenous fistula were visualized on MRA. The subcutaneous
hyperintense signal disappeared within the left orbit, indicating that the subcutaneous hemorrhage
was absorbed. A radiologist suggested the possibility of varix or hemangioma, but as the patient did
not complain of left eyelid swelling, left eye pain, or other subjective symptoms at that time, watchful
waiting was continued.
One month later, the left eye pain recurred. Contrast-enhanced MRI was considered to berequired for differential diagnosis, and was therefore performed. The size and shape of the lesion
were unchanged from the previous scans (Fig. 4A). In dynamic contrast-enhanced MRI, the lesion
started to exhibit contrast enhancement slowly after the sinus venosus, becoming enhanced at almost
the same time as the superior ophthalmic vein, and showed strong contrast enhancement in theequilibrium phase. The lesion increased in size when the patient was prone (Figs. 4B and 4C). Basedon the ﬁndings that the lesion had slow blood ﬂow and increased in size with the prone position, andthe lack of demonstrable arterial supply to the lesion, OVM was diagnosed.
After that, she repeatedly complained of left orbital pain without other clinical symptoms even if
she changed body positions, so she was referred to the department of neurosurgery for surgicaltreatment. However, angiography did not visualize any vascular inﬂow into the orbital tumor, andthe decision was made to keep the patient under surveillance without treatment.

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Orbital Venous Malformation with Obscure Clinical Symptoms

Figure 1. A 54-year-old woman presented with mild subcutaneous hemorrhage of the right eyelid, but eyelid swelling
had improved compared to her ﬁrst visit. No other objective signs were present.

Figure 2. Initial MRI reveals a lesion in the extraconal medial rectus oculi muscle and ethmoid sinus wall within
the left orbit (arrows). The lesion appears hypointense on axial T1-weighted image (A) and hyperintense on axial T2weighted and short T1 inversion recovery (STIR) image (B). The lesion is hyperintense on coronal STIR image (C).
Coronal STIR image shows a subcutaneous hyperintensity within the left orbit (D).

- 93 -

Kyo et al

Figure 3. Half a month after her ﬁrst visit, precontrast MRI shows that the lesion has increased in size since theinitial coronal short T1 inversion recovery image (A). The lesion appears to have a lobulated shape with ill-deﬁned
edges on T2-weighted image (B).

Figure 4. One month after her ﬁrst visit, the size and shape of the lesion were unchanged from previous scans in thesupine position on short T1 inversion recovery image (A). The lesion appears larger in the prone position (C) than in
the supine position (B) on coronal contrast-enhanced T1-weighted fat-suppressed MRI.

- 94 -

Orbital Venous Malformation with Obscure Clinical Symptoms

Discussion
Vascular malformations are subdivided into capillary, venous, lymphatic, arteriovenous, andcombined malformations, depending on the dominant vasculature according to the criteria of theInternational Society for the Study of Vascular Anomalies (ISSVA)1).
Venous malformations show sluggish blood ﬂow through malformed vessels, and distensible OVM
reportedly demonstrates an initial small nidus of filling in the pre-Valsalva arterial phase, with
progressive filling and expansion in the subsequent Valsalva venous phase. Nondistensible OVM
shows no dilation with the Valsalva maneuver 2). Usually patients with OVMs complain of thepresence of a mass (42%), proptosis (37%), or hemorrhage around the eyelids (15%), then the lesion isdetected by performing imaging examinations. CT, MRI, vascular angiography, and other forms of
diagnostic imaging are typically used to diagnose OVMs2). One study reported that proptosis or eyelid
swelling appeared or worsened during the Valsalva maneuver in 52% of cases of orbital arteriovenous
malformation3).
In the present case, although main initial complaints were eye pain and eyelid swelling, the only
objective ﬁnding was slight subcutaneous hemorrhage, and no exophthalmos or eyelid swelling wasapparent even during the Valsalva maneuver. However, since pain around the eyelid recurred several
times after the hemorrhage was reabsorbed, we carried out some imaging examinations. In dynamic
contrast-enhanced MRI, the lesion slowly started to exhibit contrast enhancement after the sinus
venosus, becoming enhanced at almost the same time as the superior ophthalmic vein, and showedstrong contrast in the equilibrium phase. However, no abnormal arterial inﬂow into the orbit was
identiﬁed during angiography. In addition, the lesion enlarged with the patient in a prone position.
This OVM might have been a borderline type between distensible and nondistensible, because thelesion showed negative response to the Valsalva maneuver but positive response to the prone position
during imaging. Imposition of a challenge such as a change in body position may thus enabledeﬁnitive diagnosis in such patients who complain of deep eye pain in the absence of other obvious
clinical symptoms.
OVMs that present as intolerable pain, functional defect (usually caused by acute profoundhemorrhage), repeated hemorrhage, or chronic cosmetic disﬁgurement are managed selectively4). If
intervention is indicated, management options for OVM include sclerotherapy, embolization,
detachable coils, laser therapy, or surgical excision2,4,5). In the present case, no obvious OVM was
visualized by angiography and the condition was therefore left untreated. The size of OVM may
inﬂuence whether treatment is indicated.
One issue in this case was that because orbital cellulitis was initially suspected, the possibility of
OVM was not raised, and contrast-enhanced imaging or challenges were not used to try to makediagnostic imaging more effective.
Acknowledgements
All authors have no COI to declare regarding the present study.
References
1. International Society for the Study of Vascular Anomalies. ISSVA classiﬁcation for vascular anomalies. https://www.issva.org 2014.
2. Li T, Jia R, Fan X. Classiﬁcation and treatment of orbital venous malformations: an updated review. Front- 95 -

Kyo et al
Med 2019;13:547-555.
3. Wright JE, Sullivan TJ, Garner A, et al. Orbital venous anomalies. Ophthalmology 1997;104:905-913.
4. Arat YO, Mawad ME, Boiuk M. Orbital venous malformations: current multidisciplinary treatment approach.
Arch Ophthalmol 2004;122:1151-1158.
5. Benoiton LA, Chan K, Steiner F, et al. Management of orbital and periorbital venous malformation. Front
Surg 2017;4:27.

- 96 -

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