Conventionally, when carrying out IM injections, areas featuring more highly developed muscles are chosen, and certainly to inject into the muscle has been considered crucial. Possible sites for the adult IM injection include: deltoid, dorsogluteal, and ventrogluteal muscles (Figure 1(a), and Figure 1(b)) [21] .

In clinical practice in Japan, the principal methods for assessing appropriate IM injection sites of the buttocks are the dorsogluteal four and three-way split method [22] and double cross method [23] [24] . However, since the four and three-way split method point involves an area proximal to where the superior gluteal artery has many branches in the buttocks, particular care must be taken to avoid not only nerve damage, but also blood vessel puncture [22] . The double-cross method [23] [24] is a method which was proposed to avoid the risk of nerve injury to the sciatic nerve [25] [26] . However, it is close to the four-three way split method point, so caution is required for the aforementioned reasons. In addition, there are also the Hochstetter and Clark points located on the ventrogluteal site [27] . All these methods are specialized methods for the IM injection regions proposed in the 1960s [26] , and no revolutionary injection site selection methods have been proposed since. These injection site assessment methods are a guide to IM injection penetration points, at which it should be theoretically and experientially difficult to damage nerves or blood vessels if one were to administer an injection at these points.

It is however necessary to be mindful of the fact that given individual differences in physique and pelvis shape [28] , inappropriate penetration direction or depth can cause problems.

The three finger breadths below the acromion is selected as the site for the deltoid IM injection site. Although opinion is divided, the shortest distance from the acromion to the axillary nerve is said to be 5 cm. Given the close proximity of the deltoid IM injection site to nerves and blood vessels, it is especially important to correctly understand anatomical physiology and be mindful of safety. There are examples of the deltoid branch of the axillary muscle and blood vessels running through the thickest section, previously determined by inspection and palpation to have sufficient muscle [22] . Moreover, there are also reports of vaccination-related shoulder dysfunction due to injection into the upper third of the deltoid muscle [29] . It is crucial to accurately determine the position of the acromion which serves as an indicator in ascertaining the safe area of the deltoid muscle, while paying heed to patients’ individual differences (sex, physique, body-mass-index etc.) [30] .

Therefore, it is becoming increasingly important for clinicians to identify a safer IM injection site in the deltoid muscle because of possible complications following the vaccine administration of IM injections [31] .

In order to administer the drug into the gluteus medius muscle, the entire injection needle tip needs to reach the sub fascial, and it is important to assess the distance to the targeted gluteus medius muscle [32] .

Using an ultrasound diagnostic device to measure the thickness of subcutaneous fat, Kikuchi et al. [33] reported figures for subjects under 65 years of age, at the four and three-way point, such as males: 1.05 ± 0.43 cm and females: 1.41 ± 0.48 cm.

From the results of their cadaver dissections, Sato et al. [34] reported that for 11 out of 32 cases the gluteus maximus muscle was distributed at the four and three-way point. For subjects whose gluteus maximus muscle was found to overlay the gluteus medius muscle, the distance to the gluteus medius muscle from the skin was 3.8 ± 2.3 cm, however, in patients without the distributed gluteus maximus muscle, the distance was 1.6 ± 0.8 cm. Thus, it is necessary to determine an injection needle depth with respect to the presence or absence of gluteus maximus muscle distribution, if one intends the needle point to reach the gluteus medius muscle at this injection site.

The distance to the gluteus medius muscle is determined by two factors; the thickness of subcutaneous fat directly beneath the injection site, and the presence or absence of the gluteus medius muscle (whether the gluteus maximus is atop the gluteus medius or not). Notwithstanding, results of dorsogluteal measurements for Japanese subjects are available. Given that physique differs according to ethnicity, there is a need to refer to national averages for physique, when regarding survey results.

While there are various types of injection needles available, in the case of IM injection, 21 - 23G injection needles are used, and for oil-based formulations 21G, 1.1/2 (38 mm) RB (regular bevel) is preferable.

Nevertheless, the majority of nurses working in the psychiatric department used the 23G, RB 1.1/4 injection needle (32 mm) [35] . When using a 23G, RB 1.1/4 injection needle (32 mm) to administer an IM injection at the four and three-way split method site, even if the needle were inserted to the base, there is a possibility that it may not reach the gluteus medium muscle, and the drug may be injected into the subcutaneous or gluteus maximus muscle [36] [37] . Therefore, it is thought that when selecting a four three-way split method site, and injecting the buttocks presenting with thick subcutaneous fat, it may be necessary to employ long 22G1.1/2 (38 mm) needles [38] .

In some cases, if the insertion depth is shallow than as expected, IM injection needle may not penetrate the muscle fascia. However, if needle insertion depth is deeper than anticipated, needle penetration may cause damage to nerves, arteries and veins. This provided the authors the impetus to evaluate the suitable depth of injection needles [11] . The plasma 9-hydroxyrisperidone (9-OH-RIS) concentrations were measured every two weeks. Comparison data were determined on the 8th week and the 14th week. No significant difference was observed in 9-OH-RIS concentrations, psychotic symptoms, of subjects in both groups. Also, with the 50 mm needle insertion group, injection site adverse reactions were confirmed in two subjects (15%). Also, in the 20 mm needle insertion group, injection site reactions were confirmed in six subjects (46%). Although effective 9-OH-RIS concentrations were obtained with the insertion site using both depths, it was found that the 50 mm insertion length was more suitable for dorsogluteal IM injections in adult patients with schizophrenia as demonstrated by the incidence of local adverse skin reactions.

As shown in Figure 2, there are individual differences in muscle mass volume and body fat percentage. In particular, this point needs to be taken into consideration when doing IM injection.

The patients’ daily activity levels vary, with some engaged in employment and some not. Furthermore, while there are reports of obesity trends due to increased appetite and reduced motivation side-effects of the anti-psychotic medication [39] , there are also reports of weight loss due to reduced appetite in conjunction with mental and physical symptoms (swallowing disorders, masticatory disorders) [40] .

There is a possibility of differences in body fat and muscle volume for healthy women using LAI for infertility treatments or contraceptives, and patients undergoing sustained treatment for schizophrenia.

Figure 3 shows an ulutorasonographic image at dorsoglutal site, visible from the top, skin surface, subcutaneous tissue, fascia, gluteus muscles and ilium.

Figure 4 shows an image by ultrasound diagnostic device of the deltoid IM injection site (Right side). Visible from the top are the epidermis, subcutaneous tissue, muscle membrane, muscle and humerus.

Figures 5(a)-(f) is the ultrasonographic findings during IM injection of the aripiprazole long-acting injectable antipsychotics (ALAI). The ALAI is a water-soluble suspension. It is drawn as high echogenicity on the B-mode scan. In the ultrasound image, the acoustic shadow is noted as a high range brightness toward the back. The injection needle itself casts a strong characteristically metallic acoustic shadow, so it is not possible to directly confirm the injection needle as an image, only the tip of the needle can be monitored, though its movement can be confirmed on video.

Figure 6 shows a pulsative blood flow (artery) that was detected by B-mode scan with colored Doppler image.

On duplex scan (B-mode scan with colored Doppler), arteries and veins can be detected. The lumen with colored Doppler signals suggests arteries or veins. In this case, arterial pulsatile Doppler signals were detected on duplex scan. The

lumen separated by high echogenicity lines without Doppler signals may be nerves [41] .

Surrounding the deltoid IM injection site, the thickness of the deltoid muscle, and especially the subcutaneous fat of the upper arm is thin compared to that of the buttocks. Care needs to be taken due to the numerous branches of the brachial plexus and brachial artery in the surrounding area.

The left side of Figure 7 is an image obtained by Elastography.

Elastography is an ultrasonic method for imaging the elasticity of compliant tissues [42] . By Elastography, the hardness of the tissue of the IM injection site can be evaluated, and the degree of the induration can be diagnosed. While the injection procedure performed incorrectly, especially in the cases with the needle was not inserted deeply enough to penetrate the fascia, the echogenic mass would be detected in the subcutaneous tissue on B-mode scan. In these cases, it could be a cause of focal induration and pain.

Figure 8 shows the comparison result of “Distance from the Epidermis to the Under-Fascia (DEUF)” and “Distance from the Epidermis to the Iliac Bone

(DEI)” of the four classical gluteal IM injection sites. It is important to be mindful of the fact that DEI changes depending on injection site. In the interest of being concise, only the left side of the buttock is shown since there was almost no difference in sides. Please refer to the references for details [14] .

Before preparing for the procedure, it is necessary to verify, by enclosed package pamphlet and interview form, the necessity or not of massage, the properties of the medicine, meticulous, and usage. For medications which do not require massage, it is important to communicate this information to the patient for the purpose of ensuring optimum drug efficacy. Moreover, when carrying out repeated IM injections, the previously employed injection site and administered volume should be verified from the patient record, and the opposite side or alternate site selected for use.

When utilizing the gluteal IM injection sites, patient position at administration will differ depending on the site. Prone position is necessary for the four and three-way split method point and Double-cross site, while the Hochstetter site allows for lateral or standing position. In addition, both lateral and prone positions are possible for the Clerk site.

However, results from a study of females with average physique [30] indicated that for the Hochstetter site, skinfold thickness in supine position was 0.7 cm thicker than in lateral position. In consideration of this, skinfold thickness is thought to change depending on whether administering at the Hochstetter site in standing or lateral position.

When administering at the deltoid muscle, 5 cm below the acromion, slightly above the point three finger widths below the acromion, is considered to be safe in order to avoid damage to nerves or blood vessels [43] . It is important to use a tape measure and ensure that physicians and nurses understand the three-finger width measurement in order to select the most suitable point. Due to differences in height, weight and muscle volume between patients, the buttocks should be maintained as an option in cases where muscle volume is low or medication volume is high. Furthermore, it is important to verify the absence of swelling, redness and induration by palpation, as well as feelings of pain or discomfort by the patient.

Due to the proximity of the superior gluteal artery and nerve to the four and three-way split method and the double cross sites of the gluteus medius muscle, it is crucial that the absence of numbness, severe pain and blood in the syringe is confirmed before injecting the drug. Moreover, even after injection, it is important to check for presentation of delayed paralysis as part of the safety procedures for carrying out IM injections. As a rule, direction of the needle should be at 90 degrees to the skin in order to ensure the entire tip reaches the appropriate area.

When carrying out IM injections, the syringe should be held in the dominant hand, piercing perpendicular to the skin, using the pen-holding method as a means of keeping it steady.

Before injecting the medicine, it is crucial to verify with the patient that there is no numbness or severe pain. Pull back slightly on the plunger to check the absence of blood, if there is blood, withdraw the needle and stop the bleeding. When injecting the medicine, do not change hands, keep the syringe steady so as not to alter the direction or depth of the needle, use the opposite hand to deliver the medicine.

When administering IM injections at the deltoid injection site, it is important to maintain a posture where the syringe can be held steady, so as to ensure that the entire injection needle tip reaches the appropriate area. When physicians and nurses administer the injection needle by standing position, it is possible that the tip of the needle could enter the area proximal to the deltoid branch of the axillary nerve. To avoid risk factors such as nerve and blood vessel damage, and injecting a site different from that assessed, physicians and nurses should sit on a chair or something to administer the injection.

Physicians and nurses should always wear gloves to comply with standard precautions against infection.

Factors influencing IM injection administration:

1) Needle-based factors: kinds of syringes, injection needles, drugs.

2) Factors about the patients: Optimum constant posture can be obtained, selection and condition of injection site; a) Condition such as physique, subcutaneous fat, muscle mass, skin, b) Neurological factors: the nerve conditions requiring attention, blood circulation surrounding the blood vessels (in the vicinity of the injection penetration site), and c) Subcutaneous tissue and muscular condition at the injection site by injecting liquid medicine as previously noticed.

3) Knowledge shared by physicians and nurses need to be enforced: Knowledge of the anatomical positions of skin and muscles, and the nerve and vessel circulatory health require attention, enforcing muscle injection guidelines (penetration point, depth, direction), and urgent judgment at the time of implementation of procedures.