Intramuscular injections can cause damage to arteries, veins and nerves. Achieving maximum effects of medications through precise intramuscular (IM) injections must be assured and with certainty, particularly with long-acting injection drugs (LAI). The purpose of this study is to determine precision in IM LAIs of patients with schizophrenia. These evidences estimate “Distance from the Epidermis to the Under-Fascia” (DEUF) and “Distance from Epidermis to the Upper-Arm Bone” (DEB) of the deltoid muscle. Explanatory variables include body height, weight, body-mass index (BMI), deltoid-muscle circumference, fat percentage and muscle mass measured by body composition monitor. Sixty nine subjects are included based on the Diagnostic Statistical Manual of Mental Disorders (DSM-IV, 1994), and receive treatments of typical and atypical antipsychotic LAI. There are 46 males and 23 females with average age of 51.41 (Standard Deviation = 13.58) and ranging from 21 to 81 years who are all right-handed. Ultrasonographic data and those from explanatory variables are calculated using Spearman’s rank correlation coefficients. Multiple regression analysis (step-wise method/forced input method) is performed assuming DEUF or DEB as dependent variables. Significant correlations are found with highest adjusted R-square. Paired t-tests show differences in average values of actual ultrasonographic measurements assigned to DEUF or DEB, and the regression equations for accuracy. Ultrasonographic values are assigned multiple-regression equations as true values, and the calculated values are compared with those obtained by regression equations. There are no significant differences observed for either the right or left arm. The multiple regression equations for BMI and fat percentages (upper extremity estimation) of DEUF, and for BMI and injection site circumference of estimated DEB, successfully value the DEUF and DEB. By using these multiple regression equations for IM injection to the deltoid-muscle, DEUF can better ensure accurate LAI into the muscle through body monitor, DEB, and measured values of the deltoid-muscle injection site circumference.
As the muscular layers are under the subcutaneous tissue, muscle injections carry a high risk of damages to the arteries, veins and nerves as compared with intradermal injection and subcutaneous injection [
In Japan, common vaccinations are performed through subcutaneous injection, but are done intramuscularly in other countries [
Most cases of schizophrenia are chronic conditions in which a continuous life-long drug dosing is often required for the prevention of recurrence. If the symptoms can be controlled by drug therapy, the patients can live their daily lives in their own community. Therefore, their quality of life is dependent on whether or not they can continue their drug therapy. However, for the treatment of patients with schizophrenia, because of their poor understanding of their own disease, continuing drug therapy is said to be difficult. Therefore, an atypical antipsychotic long-acting injection (LAI) into the muscle from which a sustainable and stable therapeutic effect can be expected for a certain period is a priority [
LAI is designed to be dissolved and to decompose at the muscle injection site and disseminated into the general circulation for several weeks [
The deltoid muscle and gluteal medius muscle are often selected for muscle injection in psychiatric cases as with other conditions [
As the three fingers’ breadth below the acromion is affected by the thickness of the fingers of those who perform the injection, the deltoid muscle injection site becomes different according to the practitioners’ fingers. The site of “three fingers’ breadth below the acromion” is possibly affected by the individual differences of muscle and finger breadths of both the practitioners and the patients’ gender, physical constitution, BMI (Body mass index), etc. [
Among the research conducted on the needle insertion depth in the deltoid muscle, there is research that uses ultrasonography targeting health people. Kikuchi et al. [
All the preceding research studies targeted healthy people. No research studies targeting actual patients with schizophrenia have been conducted. However, there is a report that the prevalence of obesity is high among patients with mental illness [
The purpose of this research was to determine the possibility of estimating the “Distance from the Epidermis to the Under-Fascia (DEUF)” and “Distance from Epidermis to the Upper-Arm Bone (DEB)” of the deltoid muscle injection site for patients with schizophrenia, using the explanatory variables of body height, body weight, BMI, deltoid-muscle injection site circumference and fat percentage, and muscle mass measured by a body composition monitor.
The subjects met the diagnostic standard of schizophrenia of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSV-IV: the American Psychiatric Association, 1994). The inclusion criteria were patients had an injections of a LAI therapy who were ≥18 years of age. Exclusion criteria included an active alcohol or substance abuse, or current pregnancy/lactation. They were patients with schizophrenia receiving treatment of typical and atypical antipsychotic long-acting injection (LAI) in the two hospitals in Kumamoto Prefecture and Aichi Prefecture, Japan. The number of hospital beds and the average length of a hospital stay are following: hospital in Kumamoto Prefecture (234 beds and 231 days), and hospital in Aichi Prefecture (315 beds and 132 days). The number of subjects were 69 (46 males and 23 females) with an average age of 51.41 (Standard deviation = 13.58), and ranging from 21 to 81 years. Amount muscles may differ depending on the diffe- rence in the dominant hand, all subjects were right-handed. The subjects agreed to participate in the research.
A prospective cross-sectional study was conducted, and period was from June 2012 to October 2013.
An ultrasonography machine of HI VISION AVIUS (Hitachi-Aloka Medical Co. Mitaka City) and a linear probe with a frequency of 735 MHz were used. The measurement was conducted by an expert clinical laboratory technologist. The site at three fingers’ breadth below the acromion, which is considered to be an appropriate deltoid muscle injection site at present [
The circumference of the injection site was marked using a ruler.
Body height (cm), body weight (kg), BMI (kg/m2), fat percentages (%) of the whole body, body trunk, left upper extremity and right upper extremity (hereafter referred to as “fat percentage”), and the muscle masses (kg) of the whole body, body trunk, left upper extremity and right upper extremity (hereafter referred to as “muscle mass”) were measured using a body monitor (InnerScan®50V-TANITA).
Spearman’s rank correlation coefficients of the DEUF and DEB measurement data by ultrasonography and the items of body height, body weight, BMI, muscle mass, fat percentage and deltoid-muscle injection site circum ference were calculated. Multiple regression analysis (stepwise method/forced input method) was performed assuming DEUF or DEB as the dependent variable, and the aforementioned items in which significant correlation were recognized as explanatory variables. The results indicated an adjusted R2 as highest was employed. A paired t-test was conducted to test the difference in average values of the actual ultrasonographic measured values assigned to DEUF or DEB and the regression equation for the purpose of establishing accuracy of data. The ultrasonographic measured values and predicted value by regression equation was calculated by Pearson product-moment correlation coefficient. Power analysis for a multiple regression with two predictors was conducted in G*Power to determine a sufficient sample size using an alpha of 0.05, a power of 0.80, and a medium effect size (f2 = 0.15). Based on the aforementioned assumptions, the desired sample size was 55.
This research was conducted with the approval (approval number 2948) of the Ethical Committee of the Tokushima University Hospital. The cooperative hospitals were asked to have their primary doctors select candidates for this research among their patients with schizophrenia under LAI treatment. Then, the collaborators explained the purpose, contents and method of this research study verbally and in writing to the prospective subjects. Those who consented to participate were regarded as subjects. The following were described in the consent letter: 1) the subjects’ agreement to participate out of their own free will; 2) if they agree to participate in this research, they can discontinue it at any time; and 3) no disadvantage will be caused by cancellation of participation and cooperation.
The correlations between the right and left DEUFs and the variables of body height, body weight, BMI, fat percentage, muscle mass and deltoid muscle injection site circumference are shown in
The correlations between the right and left DEBs and the variables of body height, bodyweight, BMI, fat per-
Item | Mean | Standard Deviation | Minimum | Maximum | ||
---|---|---|---|---|---|---|
Basic Information | Age | 51.41 | 13.58 | 21.00 | 81.00 | |
Height (cm) | 164.20 | 7.89 | 146.10 | 179.00 | ||
Weight (kg) | 69.72 | 14.80 | 39.20 | 105.60 | ||
BMI (kg/m2) | 25.72 | 4.73 | 17.27 | 39.70 | ||
DMISC (cm) | Left | 34.51 | 4.59 | 23.40 | 47.20 | |
Right | 34.65 | 4.93 | 23.90 | 47.20 | ||
Measurement by ultrasonography | DEUF (mm) | Left | 7.67 | 2.47 | 3.50 | 17.20 |
Right | 7.73 | 2.35 | 3.80 | 18.50 | ||
DEB (mm) | Left | 27.69 | 6.79 | 12.20 | 44.80 | |
Right | 26.12 | 6.35 | 12.70 | 47.50 | ||
Measurement using a body monitor | Fat percentage (%) | Whole body | 33.70 | 13.54 | 8.30 | 62.90 |
Body trunk | 30.05 | 10.41 | 14.00 | 61.90 | ||
Left upper extremity | 21.93 | 10.00 | 1.90 | 49.10 | ||
Right upper extremity | 23.22 | 9.23 | 7.10 | 18.30 | ||
Muscle mass (kg) | Whole body | 41.97 | 12.30 | 15.90 | 69.55 | |
Body trunk | 26.03 | 9.02 | 10.60 | 51.80 | ||
Left upper extremity | 2.30 | 0.55 | 1.20 | 3.40 | ||
Right upper extremity | 2.15 | 0.58 | 1.05 | 3.50 |
BMI: Body Mass Index; DMISC: Deltoid Muscle Injection Site Circumference; DEUF: Distance from the Epidermis to the Under-Fascia; DEB: Distance from the Epidermis to the Upper-Arm Bone; N = 69, 46 (67%) of the patients were males, and 23 (33%) were female.
Ultrasonography | |||||
---|---|---|---|---|---|
DEUF | DEB | ||||
Left | Right | Left | Right | ||
Height (cm) | −0.064 n.s. | −0.194 n.s. | 0.094 n.s. | 0.201 n.s. | |
Weight (kg) | 0.520** | 0.508** | 0.636** | 0.748** | |
BMI (kg/m2) | 0.630** | 0.667** | 0.691** | 0.751** | |
DMISC (cm) | Left | 0.459** | - | 0.577** | - |
Right | - | 0.496** | - | 0.679** | |
Body monitor | |||||
Fat percentage (%) | Whole body | 0.263* | 0.378** | 0.290* | 0.327** |
Body trunk | 0.581** | 0.426** | 0.288* | 0.296* | |
Left upper extremity | 0.505** | - | 0.275* | - | |
Right upper extremity | - | 0.591** | - | 0.168 n.s. | |
Muscle mass (kg) | Whole body | 0.250* | 0.142 n.s. | 0.213 n.s. | 0.259* |
Body trunk | 0.061 n.s. | 0.230 n.s. | 0.286* | 0.328** | |
Left upper extremity | 0.098 n.s. | - | 0.456** | - | |
Right upper extremity | - | −0.042 n.s. | - | 0.398** |
BMI: Body Mass Index; DMISC: Deltoid Muscle Injection Site Circumference; DEUF: Distance from the Epidermis to the Under-Fascia; DEB: Distance from the Epidermis to the Upper-Arm Bone; Spearman Rank correlation coefficient: *p < 0.05, **p < 0.001; n.s.: Not significant.
centage, muscle mass and deltoid muscle injection site circumference are shown in
Relationship between DEUF and both BMI and fat percentage of the upper extremity
The analytical results of the relationships between the left and right DEUFs, and BMI and body fat percentage of the upper extremity are shown in
As a result, as the adjusted R2 of both arms were the highest as a multiple regression equation for calculating DEUF, it was employed as a prediction expression.
Left DEUF y = −1.481 + 0.318 × BMI + 0.044 × fat percentage (left arm) (1)
Right DEUF y = −1.302 + 0.278 × BMI + 0.081 × fat percentage (right arm) (2)
Relationships between DEB and both deltoid-muscle injection site circumference and BMI
The analytical results of the relationships between the left and right DEBs, and deltoid-muscle injection site circumference and BMI are shown in
As the adjusted R2 of both arms were the highest as a multiple regression equation for calculating DEB, it was employed as a prediction equation.
95% confidence interval | ||||||||
---|---|---|---|---|---|---|---|---|
PRC (B) | SPRC (β) | R2 | Adjusted R2 | Minimum | Maximum | Probability | ||
Constant terms | −1.481 | 0.518 | 0.503 | −3.837 | 0.875 | n.s. | ||
Left | BMI | 0.318 | 0.608 | 0.213 | 0.094 | ** | ||
DEUF | Fat percentage (left arm) | 0.044 | 0.180 | −0.005 | 0.423 | n.s. | ||
Constant terms | −1.302 | 0.589 | 0.577 | −3.349 | 0.746 | n.s. | ||
Right | BMI | 0.278 | 0.560 | 0.189 | 0.368 | ** | ||
DEUF | Fat percentage (right arm) | 0.081 | 0.318 | 0.035 | 0.126 | * |
PRC: Partial regression coefficient; SPRC: Standard partial regression coefficient; DEUF: Distance from the Epidermis to the Under-Fascia; BMI: Body Mass Index; n.s.: Not significant, *p < 0.05, **p < 0.001.
95% Confidence interval | ||||||||
---|---|---|---|---|---|---|---|---|
PRC (B) | SPRC (β) | R2 | Adjusted R2 | Minimum | Maximum | Probability | ||
Left DEB | Constant terms | −0.391 | 0.504 | 0.489 | −9.637 | 8.855 | n.s. | |
BMI | 0.998 | 0.696 | 0.503 | 1.493 | ** | |||
L-DMISC | 0.024 | 0.016 | −0.485 | 0.534 | n.s. | |||
Right DEB | Constant terms | −1.888 | 0.589 | 0.577 | −9.163 | 5.388 | n.s. | |
BMI | 0.746 | 0.555 | 0.304 | 1.187 | * | |||
R-DMISC | 0.300 | 0.233 | −0.124 | 0.724 | n.s. |
PRC: Partial regression coefficient; SPRC: Standard partial regression coefficient; L-DMISC: Left deltoid-muscle injection site circumference; R-DMISC: Right deltoid-muscle injection site circumference; DEB: Distance from the Epidermis to the Upper-Arm Bone; BMI: Body Mas Index; n.s.: Not significant, *p < 0.05, **p < 0.001.
Left DEB y = −0.391 + 0.998 × BMI + 0.024 × left deltoid-muscle injection site circumference (1)
Right DEB y = −1.888 + 0.746 × BMI + 0.3 × right deltoid-muscle injection site circumference (2)
As shown in
As shown in
The relationship between the values assigned to the DEB multiple regression equation and the values measured by ultrasonography, and the relationship between the values assigned to the DEUF multiple-regression equation and the values measured by ultrasonography are shown in
Calculated values by regression equation | Measured values by ultrasonography | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Mean | SD | Range | Mean | SD | Range | t-value | P-value | ||||
Deltoid muscle DEUF | Left | 7.663 | 1.777 | 4.620 | 13.050 | 7.668 | 2.472 | 3.500 | 17.200 | −0.027 | 0.978 |
Right | 7.728 | 1.806 | 4.440 | 13.230 | 7.729 | 2.351 | 3.800 | 18.500 | −0.005 | 0.996 |
Paired t-test; SD: Standard Deviation; DEUF: Distance from the Epidermis to the Under-Fascia.
Calculated values by regression equation | Measured values by ultrasonography | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Mean | SD | Range | Mean | SD | Range | t-value | P-value | ||||
Deltoid muscle DEB | Left | 26.104 | 4.817 | 17.500 | 40.360 | 26.119 | 6.789 | 12.200 | 44.800 | −0.026 | 0.980 |
Right | 27.693 | 4.877 | 18.170 | 41.890 | 27.693 | 6.354 | 12.700 | 47.500 | 0.000 | 1.000 |
Paired t-test; SD: Standard Deviation; DEB: Distance from the Epidermis to the Upper-Arm Bone.
The correlation with DEUF of which is recognized, is a BMI showing the degree of obesity obtained from body weight and body height [
From the result of a comparison of adjusted R2, DEUF and the value calculated by the multiple regression equation, the prediction equation with explanatory variables of BMI and fat percentage (upper extremity) was considered to be able to accurately estimate DEUF at the deltoid muscle injection site. In this research, there were cases where DEUF epidermis, measured by ultrasonography, was longer than that estimated by multiple regression equation. There were six cases where the needle was estimated to reach only up to more than 2 mm before the target in subjects’ right arms, eight for the left arm, and the maximum error was 5.2 mm. Three subjects among the six were among the four whose DEUF was determined to be thick by ultrasonic measurement. When a prediction equation is used, if the thickness of subcutaneous tissue is more than 10 mm, it is possible that the needle does not reach the muscle layer.
In order to discuss a multiple regression equation of DEB, a multiple regression analysis was performed by
forced input method regarding deltoid muscle injection site circumference and BMI as explanatory variables. It is considered that by using a combination of the deltoid muscle injection site circumference and BMI measured by a ruler, multi regression Equation (1) acquired the prediction accuracy of R2 of 0.489 and multi regression Equation (2) acquired that of R2 of 0.577. In order to further confirm the accuracy of the multiple-regression equations obtained, the DEB of the deltoid-muscle injection site as a true value was compared with the actual measured value assigned to the regression equation, and as a result, no statistic difference was observed.
The maximum error was approximately 13.6 mm on the right side, and 12.2 mm on the left side. As being discussed in preceding research [
Takahashi et al. [
The prediction equation obtained in this research is considered to be useful as a method to assess the injection sites from which the injection needle can certainly reach the muscle layer and does not harm the upper-arm bone. However, when using the estimation equation DEB, it is important to take the value of BMI and the thickness of the subcutaneous tissue into consideration.
Although the research result of Takahashi et al. [
This research targeted the patients with schizophrenia under LAI treatment. The subjects of this research were all right-handed. It is considered that depending upon whether right-handed or not, the frequency of use of muscle when carrying things and how to exert strength become different, and it makes a difference in muscle mass; therefore, it is necessary to increase the number of subjects to examine how whether right-handed or not exerts influence DEUF and DEB. In order to confirm the accuracy of the multiple regression equation obtained in this research, it is required to collect the data of the presence and degree of error between the predicted values and those measured by ultrasonography and other measurements. Furthermore, it is also required to proceed with the discussion of safety of the method for determining an injection site using the patients’ own three fingers’ breadth.
As challenges for the future, it is necessary to enhance the accuracy of the estimate equation, multivariate analyses that include the disease duration of schizophrenia and level of disease of these patients.
The research confirmed that correlations between DEUF and DEB were measured by ultrasonography, and the fat percentage and muscle mass were measured by body monitor, and the injection site circumference was measured by a ruler for the first time survey report.
The multiple regression equation obtained regarding BMI and fat percentage (upper extremity) as explanatory variables for the estimation of DEUF, and the multiple regression equation obtained regarding BMI and injection site circumference as explanatory variables for the estimation of DEB, could estimate DEUF and DEB, respectively.
By using these multiple regression equations, for muscle injection to the deltoid-muscle injection site, DEUF could better ensure medical liquid injection into the muscle, owing to the values measured by body monitor, and DEB, owing to the measured value of the deltoid-muscle injection site circumference.
The authors would like to thank subject patients and all staff members of the hospital who have helped this research.
ShigeakiMasuda,SakikoSakamaki,YukoYasuhara,YuerenZhao,KensakuTakase,YoshihiroKai,TetsuyaTanioka,Rozzano C.Locsin, (2016) Explanatory Variables as Evidence for Precision in Intramuscular Long-Acting Injections of Patients with Schizophrenia. Open Journal of Psychiatry,06,125-134. doi: 10.4236/ojpsych.2016.61015