Subcutaneous or intramuscular? Confronting a parenteral administration dilemma

Subcutaneous or intramuscular? Confronting a parenteral administration dilemma

Julie Prettyman

The first listed goal of the American Nurses Foundation is to advocate for the health of the public (American Nurses Foundation, n.d.). Evaluating the optimal route of drug administration and recommending a preferred route, when one is available, are part of the nurse’s responsibility to the patient and to the health care team. The following discussion of advantages and disadvantages of intramuscular and subcutaneous injections should help the nurse to evaluate the decision concerning the most appropriate injection route for patients.

Definitions

Intramuscular (IM) injections are given deep into skeletal muscles, typically into the gluteal, deltoid, rectus femoris, or vastus lateralis muscles (AstraZeneca Oncology, 2003; Woods & Kabat, n.d.). The choice of injection site is based on a desire to minimize the chance of the needle hitting a nerve or blood vessel. IM injections are also given based on the injection volume and other factors, including the viscosity and irritancy of the formulation (Ansel, Allen, & Popovich, 2004). Subcutaneous (SC) injections pierce the epidermal and dermal layers of the skin and deliver the drug into the loose subcutaneous tissue. SC injectable products are typically prepared as aqueous solutions or as suspensions. Following injection, the drug enters the capillaries by diffusion or filtration (Ansel et al., 2004).

Applications

Each route of administration has advantages and disadvantages (see Table 1). Based on these features, as well as on drug formulation, certain drugs must be administered by one route only, while others may be given by more than one route (see Table 2). Greater injection volumes (2 to 5 ml) may be given by the 1M route (Ansel et al., 2004; Wilkinson, 2001). However, because of the distance from the skin surface to the muscle, IM administration requires a longer needle than does SC. IM injections typically use needles 1 to 2 inches in length (Woods & Kabat, n.d.).

Drugs that are not readily soluble can provide sustained action following an IM injection when delivered in suspension form. For example, one IM injection of penicillin G benzathine suspension can produce desired blood concentrations of the drug for 7 to 10 days (Ansel et al., 2004). Other drugs given by the IM route include soluble drugs, biologics, hormones such as medroxyprogesterone acetate (Depo-ProveraG) (Pharmacia & Upjohn Company, 2004), and corticosteroids.

SC injections are usually limited to no more than 2 ml (Ansel et al., 2004). The SC route is not used for drugs that are irritating to the tissue because irritants can cause pain, necrosis, and sloughing at the site of injection (Wilkinson, 2001). For patients requiring multiple doses, SC injections offer a broader range of alternative sites (Ansel et al., 2004). SC injections typically use needles 3/8 to 5/8 inches in length (Woods & Kabat, n.d.).

Drugs that must be self-administered by the patient and involve multiple dosing are routinely given by the SC route (Ansel et al., 2004). Treatment regimens may require once daily or more frequent dosing. Examples of drugs delivered SC include soluble drugs, hormones such as insulin (Ansel et al., 2004), low-molecular-weight heparins (Careinternet.net, 2003), and biologics.

Pharmacokinetic Comparison

Several factors affect the systemic absorption of a drug following parenteral injection. Among the most important factors is blood circulation to the site of absorption (Wilkinson, 2001). Increased blood flow caused by local application of heat or massage will increase the absorption rate. Conversely, decreased blood flow caused by various disease states or vasoconstrictive agents can decrease the absorption rate. Furthermore, the surface type exposed to drug (for example, stomach, intestine, airway/lungs, skin, subcutaneous tissue, muscle) influences where absorption occurs (Wilkinson, 2001). This area of absorption is determined by the route of drug administration.

The absorption rate with SC injection is constant and slow enough to allow a sustained pharmacodynamic effect (Wilkinson, 2001). Blood supply in the SC area affects absorption, so the more proximal the capillaries are to the site of administration and the more numerous the capillaries, the faster the absorption of the drug. All drug products cross capillary membranes at a faster rate than they cross other tissue membranes (Ansel et al., 2004).

While drugs may be absorbed quickly following IM injection, the absorption rate depends on blood flow at the injection site. Joggers, who have greater blood flow to their legs, may experience a much faster rate of absorption of a drug injected into the thigh than if the same dose were injected into another muscle (Ansel et al., 2004; Wilkinson, 2001). The absorption rate of an aqueous drug administered in the deltoid or vastus lateralis generally is greater than that following injection into the gluteus maximus (Wilkinson, 2001). Blood flow to a muscle can affect the absorption rate of drugs administered by IM injection. Decreased blood flow can reduce the absorption rate (DeWit, 2001; Perry & Potter, 2004). In addition, the decreased muscle mass of many older adults may result in faster absorption of drugs delivered by IM injection (AstraZeneca Oncology, 2003; DeWit, 2001; Perry & Potter, 2004). IM absorption of some drugs in infants and young children may be unpredictable due in part to insufficient muscle tone and vascularity of muscle tissue.

Studies substantiate that there is little or no difference between IM and SC injections in the delivery, absorption, and efficacy of drugs such as vaccines and hormones. In a single-blind study of men taking warfarin (Coumadin[R]), 26 subjects aged 60 years and older were randomized to receive doses of a standard trivalent influenza vaccine by either IM or SC injection (Delafuente, Davis, Meuleman, & Jones, 1998). Both groups received 0.5 ml of the vaccine, and all doses were administered in the deltoid region, whether IM or SC. Blood samples were drawn from all participants at baseline, 6 weeks, and 4 months after vaccine administration. For the purpose of this study, a three-fold increase in reciprocal titer following vaccination was considered a positive response. The number of positive responses to components of the vaccine was not significantly different between groups; therefore, the route of administration of the vaccine did not affect antibody titers. Furthermore, no significant differences in antibody titer levels were noted between groups at baseline, 6 weeks, or 4 months, but both groups had a significant increase in titer level on both follow-up visits compared with baseline. Therefore, the immunologic response to the vaccine was similar between IM and SC delivery. Subjects demonstrated significant antibody titers at 6 weeks following vaccination, and these titers were sustained at the 4-month visit. The number of subjects with positive responses was similar between groups.

In a study evaluating the tolerance and efficacy of recombinant follicle-stimulating hormone (rFSH) given by the IM versus SC route, 218 women (mean age 32 years) undergoing in vitro fertilization (IVF) were randomized to IM or SC administration of rFSH for ovarian stimulation (Out, Reimitz, & Coelingh Bennink, 1997). IM and SC doses were given in the buttock and the umbilical region, respectively. Based on the IVF parameters (number of follicles [greater than or equal to] 15 mm, number of oocytes retrieved, number of high-quality embryos, and clinical pregnancy rate per cycle), there were no significant differences between IM and SC administration. The IM and SC routes were considered equally effective for hormone administration (Out et al., 1997). A similar study of human chorionic gonadotropin (hCG) in 40 women showed that administration of hCG via the SC route produced greater serum and follicular fluid levels of hCG than when administered by the IM route (Stelling et al., 2003).

In a study designed to determine whether rFSH should be given IM or SC in obese women, 19 patients ranging in body mass indices from 19.9 kg/[m.sup.2] to 42.8 kg/[m.sup.2] were administered rFSH (Steinkampf, Hammond, Nichols, & Slayden, 2003). Serum samples of follicle-stimulating hormone (FSH) were analyzed following two doses of the drug. Each patient received one dose of rFSH via the IM route and the second dose by the SC route. Resulting data in both obese and nonobese patients showed that SC administration achieved serum concentrations of FSH similar to those achieved when rFSH was given IM (Steinkampf et al., 2003).

Administration of hepatitis B virus (HBV) vaccine was evaluated by both the IM and SC routes in 60 patients on continuous ambulatory peritoneal dialysis (Chau et al., 2004). Those in the SC group received 5 mcg of vaccine every week for a total of 10 doses. Patients in the other group received 20 mcg by IM injection initially, and at 1 and 6 months. Although the difference was not statistically significant, the sero-conversion rate was greater in the SC group (81.5%) than in the IM group (62.1%) (p=0.03). There was no difference between groups in time required to convert peak antibody to HBV surface antigen, or proportion of patients with antigen levels maintained during the 2-year observation period (Chau et al., 2004).

Administration

Ease of administration. Administration may be easier with SC than with IM injections. Although site preparation prior to injection is the same with the two routes (Woods & Kabat, n.d.), the nurse must know and be guided by anatomical landmarks for delivering IM injections. These landmarks may be difficult to determine in patients who are very obese or emaciated. Patient body mass also may dictate the required route of administration, or at least it may determine the appropriate needle length (Wilkinson, 2001). For example, patients who are emaciated may require shorter needles for IM injections because of the shorter distance between the skin surface and muscle (AstraZeneca Oncology, 2003). Because needles of smaller bore and length tend to cause less discomfort during administration, SC injection may cause less pain than an IM injection (Woods & Kabat, n.d.).

With SC injection, the nurse has a substantial, firm area of skin to hold during the injection and delivery of medication (DeWit, 2001; Perry & Potter, 2004). This helps to immobilize the injection site. More sites and a larger overall surface area are available for SC administration than for IM injection. The abdomen, arms, and legs offer sites for SC injections; sites for IM injections are limited to smaller surface areas covering the large muscles, such as areas of the thigh over the vastus lateralis and areas of the buttock over the gluteus medius (AstraZeneca Oncology, 2003). Using the thigh as an example, there is a greater surface area available for SC than IM injections. In addition, some muscles may be sensitive to touch, making them unsuitable for IM injections (AstraZeneca Oncology, 2003). Injections into muscles that are not relaxed will result in more pain and a greater tendency to bleed. Muscles that twitch during assessment of landmarks should not be used for IM injection.

Safety profile. Because of the depths below the skin surface at which the larger blood vessels are located, a SC injection is less likely than an IM injection to pierce a blood vessel (DeWit, 2001). Damage to a nerve is also less likely with SC injection, again because the major nerve fibers generally are located below the depth of penetration of SC needles (DeWit, 2001). In addition, SC injections are unlikely to make contact with bone. In contrast, IM injections carry a greater risk of causing injury to a blood vessel, nerve, or bone (Ansel et al., 2004), often causing complications of muscle contractures and nerve injury in patients (AstraZeneca Oncology, 2003; DeWit, 2001).

Complications from IM injections can include abscess formation (AstraZeneca Oncology, 2003), local induration, erythema, persistent pain, hematoma, bleeding, and, ultimately, discontinuation of drug administration (DeWit, 2001). Less common side effects can include intramuscular hemorrhage, cellulitis, tissue necrosis, and gangrene (Bergeson, Singer, & Kaplan, 1982). IM injections on occasion cause a great deal of tenderness and may damage local muscle cells (AstraZeneca Oncology, 2003), which may limit mobility for a short time. Among eiders, the problems associated with lack of mobility must be considered, even if only for a few hours or a few days. Complications from SC injections, however, are usually limited to wheal and flare reactions. More serious side effects could include abscess and tissue sloughing at the injection site (AstraZeneca Oncology, 2003; Wilkinson, 2001).

Muscle mass. The choice of giving IM or SC injections is determined, in part, by the patient’s muscle mass. Reduced muscle mass alters drug absorption from IM injections (DeWit, 2001; Perry & Potter, 2004). Moreover, IM injections can exacerbate muscle pain due to musculoskeletal disorders, especially in older adults. There is a loss of muscle tone, strength, and mass in these individuals (Inouye, 2004). If an IM injection contributes to impaired mobility in an older adult, other sequelae might include falls and joint pain from favoring the injection site.

Sarcopenia, or reduction in muscle mass, is associated with muscle weakness and increased muscle fatigability (Nair, 2000). Melton, Khosla, and Riggs (2000) evaluated the prevalence of sarcopenia and its associated morbidity and disability. Dual-energy x-ray absorptiometry scans revealed a linear decline in skeletal muscle mass in older adults of both genders, although values of muscle mass were greater among men than women. Melton et al. (2000) also noted a correlation of approximately 0.8 between height and lean body mass. Muscle mass tended to be greater in men than in women, and greater in younger rather than in older subjects. Based on measurements of body mass index, men began to lose muscle mass by the age of 55 years.

A decline in muscle strength corresponds with a decrease in muscle mass (Marcell, 2003; Nair, 2000; Yarasheski, 2003). An approximate 25% decline in muscle strength occurs between the ages of 20 and 60 years (Nair, 2000). Early data (Melton et al., 2000) showed that the prevalence of sarcopenia was approximately 22% in white men and 31% in white women over 60 years of age. The prevalence increased with age for both genders and was slightly greater for Hispanic than non-Hispanic white individuals. The prevalence of sarcopenia was 28% in men and 52% in women older than 60 years.

Other factors of aging. Neurologic symptoms of aging such as forgetfulness, fatigue, unsteady gait, and hearing difficulty may contribute to the fear that older patients experience when receiving injections. Also, older adults are vulnerable to hypothermia (Inouye, 2004) which may affect a choice in giving an injection by the SC versus IM route; health care team members can keep patients as comfortable as possible by avoiding the need to have them disrobe for IM injections when a SC injection is available and appropriate. In addition, when older adult patients can remain seated to receive an injection, dizziness and other vasovagal responses can be minimized.

Limited mobility issues. Access to IM injection sites is often hampered in patients with limited mobility who are unable to position themselves readily in the desired posture. The greater availability of SC sites overcomes this potential problem. Mobility, vascular status, and increased age play a role in the development of pressure sores; in fact, 80% of patients with pressure sores in one study were aged 65 years or older (Thoroddsen, 1999). Prevalence rates for pressure sores in hospitalized Icelandic patients were 9% in acute care hospitals and 8.8% in community hospitals. The prevalence was greater in men (11.2%) than in women (7.12%), and the mean age at pressure sore occurrence was 78.4 years (73.75 years, men; 83.4 years, women) (Thoroddsen, 1999). Cleary, pressure sores that occur as a result of limited mobility and altered vascular status cause major discomfort, increased risk for infection, and further problems with mobility, especially in hospitalized elders. Therefore, injections should be made as simple as possible in patients with limited mobility. Administration of injections by the SC route versus the IM route, when possible, may make the injection easier and more comfortable for patients with limited mobility.

Lack of mobility due to an IM injection can cause a multitude of health-related issues in older adults and those who are already mobility impaired. The pain and muscle irritation associated with injection may cause patients to decrease their already limited mobility, in turn causing injury from trying to walk with muscle pain or using inappropriate support devices to bear weight, and causing joint irritation. These issues must be considered if the injection is going to hinder the patient’s mobility even briefly.

Hematomas with anticoagulants. Individuals on anticoagulation therapy may form hematomas following IM injections. However, one study of male subjects taking warfarin showed that IM and SC injections were both well tolerated without noticeable bruising (Delafuente et al., 1998). Nurses can help reduce the incidence of hematomas by applying pressure to the site of injection after administering the drug. If bruising does occur, application of ice to the area will help (AstraZeneca Oncology, 2003).

Infection and immunosuppressants. The risk of infection is present with both SC and IM injections because the needle breaks the protective barrier of the skin and introduces the skin’s normal bacteria into the tissue beneath (Alcantara, Tucker, & McCarroll, 2002; Brown & Ebright, 2002; Rangel & Cassiani, 2000; Satyanarayana & Mathur, 2003). Injections may cause abscesses or skin and soft tissue infections. Because it is the surface of the needle that pushes bacteria through the skin and beyond the integument, a needle of larger bore and greater length will push a greater surface area of skin tissue, potentially colonized with bacteria, to a greater depth. Additionally, if a blood vessel is damaged by the needle (a more likely occurrence with an IM injection, as discussed previously), the risk of infection will be even greater if bacteria are introduced into the circulatory system. It is possible that patients taking immunosuppressants who develop an infection after an IM or SC injection may be at increased risk of adverse outcomes due to decreased immune responses (Brown & Ebright, 2002).

Quality of life and cost of therapy. Quality of life is an important variable in determining patient care. SC injections are usually less painful because of the smaller, shorter needles used, compared with IM needles. Moreover, post-injection pain is usually less with SC than with IM injection because muscle pain is not usually experienced after the former. In addition, a smaller volume of drug is delivered via SC administration. The pain associated with a SC injection does not usually cause immobility, because there is no increase in pain with activity.

Injections that need to be made frequently are often best performed by the patient. When the patient can self-administer an injectable drug, the cost savings are great and include those associated with avoiding an office or clinic visit. Also, the patient’s quality of life is disrupted to a much lesser degree by a self-administered SC injection than by an office visit which might be required for an IM injection.

Conclusion

In many cases, SC is the preferred route for administering a drug by injection. Even when IM injection is the established route for administering a certain treatment, SC injection may be a viable option. In these situations, nurses can serve as patient advocates by suggesting a change to the SC route. In helping to ensure use of the most appropriate method of drug administration, nurses will make an important contribution to improving patient care by reducing pain at the injection site, improving patient quality of life, reducing cost of patient care, and reducing the potential for infection.

Table 1.

Advantages of SC and IM injections

Subcutaneous Advantages Intramuscular Advantages

* Greater area for target * Can give greater volume of drug

injection sites. product (2 to 5 ml).

* Fewer landmarks required for * Drugs irritating to SC tissue may

targeting injection sites. be given IM.

* Shorter needles can be used

(3/8 to 5/8 inch).

* Readily self-administered.

* Good for multiple dosing.

* Muscle mass not an issue.

* Less discomfort and

inconvenience for patients

with neurological disease

or limited mobility.

* Better safety profile.

Source: Adapted from Ansel et al., 2004; Woods & Kabat, n.d.

Table 2.

Drug Routes and their Routes of Administration

Drugs given by a specific route Route

Daunorubicin (Cerubidine[R]) IV

Enoxaparin (Lovenox[R]) SC

Medroxyprogesterone acetate (Depo-Provera[R]) IM

Penicillin G benzathine and penicillin G procaine IM

(Bicillin CR[R])

Vancomycin (Vancocin[R]) IV

Drugs given by more than one route Routes

Epinephrine (Adrenalin[R]) IM/IV/SC

Naloxone (Narcan[R]) IM/IV/SC

Cyanocobalamin IM/SC

Source: Adapted from Aventis Pharmaceuticals, 2004; ISMP, 1999;

Pharmacia & Upjohn Company, 2004; Simons, Gu, & Simons, 2001;

Trissel, 2005.

References

Alcantara, A.L., Tucker, R.B., & McCarroll, K.A. (2002). Radiologic study of injection drug use complications. Infectious Disease Clinics of North America, 16, 713-743.

American Nurses Foundation. (n.d.). Mission of the American Nurses Foundation. Retrieved December 7, 2004, from http://www.nursingworld.org/anf/ mission.htm

Ansel, H.C., Allen, L.V., & Popovich, N.G. (2004). Pharmaceutical dosage forms and drug delivery systems (8th ed.). Philadelphia: Lea & Febiger.

AstraZeneca Oncology. (2003). Excerpts from nursing procedures. I.M. injection. Retrieved November 17, 2003, from http://www.breastcancerprofe ssional.com/contents/public/onc/ nursing.pdf

Aventis Pharmaceuticals, Inc. (2004). Lovenox. [package insert]. Bridgewater, N J: Aventis Pharmaceuticals, Inc.

Bergeson, P.S., Singer, S.A., & Kaplan, A.M. (1982). Intramuscular injections in children. Pediatrics, 70, 944-948.

Brown, P.D., & Ebright, J.R. (2002). Skin and soft tissue infections in injection drug users. Current Infectious Disease Reports, 4, 415-419.

Careinternet.net. (2003). Low molecular weight heparins. Retrieved November 17, 2003, from http://www.careinter net.com/caregiver/lmwh.php

Chau, K.F., Cheng, Y.L., Tsang, D.N., Choi, K.S., Wong, K.M., Chak, W.L., et al. (2004). Efficacy and side effects of intradermal hepatitis B vaccination in CAPD patients: A comparison with the intramuscular vaccination. American Journal of Kidney Diseases, 43(5), 910-917.

Delafuente, J.C., Davis, J.A., Meuleman, J.R., & Jones, R.A. (1998). Influenza vaccination and warfarin anticoagulation: A comparison of subcutaneous and intramuscular routes of administration in elderly men. Pharmacotherapy, 18(3), 631-636.

DeWit, S.C. (2001). Fundamental concepts and skills for nursing. Philadelphia: W.B. Saunders Company.

Inouye, S.K. (2004). Neuropsychiatric aspects of aging. In L. Goldman & D. Ausiello (Eds.), Cecil textbook of medicine (pp. 114-117). Philadelphia: Saunders.

Institute for Safe Medication Practices. (1999). Many wrongly believe long-acting parenteral penicillins are for intravenous injection. Retrieved December 7, 2004, from http://www. ismp.org/msaarticles/parenpcn.html

Marcell, T.J. (2003). Review article: Sarcopenia: Causes, consequences, and preventions. Journal of Gerontology Series A: Biological Sciences and Medical Sciences, 58, M911-916.

Melton, L.J., Khosla, S., & Riggs, B.L. (2000). Epidemiology of sarcopenia. Mayo Clinic Proceedings, 75, S10-12.

Nair, K.S. (2000). Age-related changes in muscle. Mayo Clinic Proceedings, 75, S14-18.

Out, H.J., Reimitz, P.E., & Coelingh Bennink, H.J.T. (1997). A prospective, randomized study to assess the tolerance and efficacy of intramuscular and subcutaneous administration of recombinant follicle-stimulating hormone (Puregon). Fertility and Sterility, 67, 278-283.

Perry, A.G., & Potter, P.A. (2004). Clinical nursing skills and techniques (5th ed.). St. Louis, MO: Mosby.

Pharmacia & Upjohn Company. (2004). Depo-Provera [package insert]. Kalamazoo, MI: Author.

Rangel, S.M., & Cassiani, S.H. (2000). Intramuscular administration of drugs: Skills of pharmacy personnel. Revista da Escola de Enfermagem da USP, 34, 138-144.

Satyanarayana, S., & Mathur, A.D. (2003). Atypical mycobacterial injection abscess. Journal of the Indian Medical Association, 101, 36-40.

Simons, F.E.R., Gu, X., & Simons, K.J. (2001). Epinephrine absorption in adults: Intramuscular versus subcutaneous injection. Journal of Allergy and Clinical Immunology, 108, 871-873.

Steinkampf, M.R, Hammond, K.R., Nichols, J.E., & Slayden, S.H. (2003). Effect of obesity on recombinant follicle-stimulating hormone absorption: Subcutaneous versus intramuscular administration. Fertility and Sterility, 80(1), 99-102.

Stelling, J.R., Chapman, E.T., Frankfurter, D., Harris, D.H., Oskowitz, S.P., & Reindollar, R.H. (2003). Subcutaneous versus intramuscular administration of human chorionic gonadotropin during an in vitro fertilization cycle. Fertility and Sterility, 79(4), 881-885.

Thoroddsen, A. (1999). Pressure sore prevalence: A national survey. Journal of Clinical Nursing, 8, 170-179.

Trissel, L.A. (2005). Handbook on injectable drugs (13th ed.). Bethesda, MD: American Society of Health-System Pharmacists.

Wilkinson, G.R. (2001). Pharmacokinetics: The dynamics of drug absorption, distribution, and elimination. In J.G. Hardman, L.E. Limbird, & A.G. Gilman (Eds.), Goodman & Gilman’s the pharmacological basis of therapeutics (pp. 3-29). New York: McGraw-Hill.

Woods, A.D., & Kabat, A.G. (n.d.). Administration of pharmaceuticals by injection: General concepts and major parenteral routes procedures. Retrieved November 17, 2003, from http://www. nova.edu/~kabat/Injection.pdf

Yarasheski, K.E. (2003). Review article: Exercise, aging, and muscle protein metabolism. Journal of Gerontology Series A: Biological Sciences and Medical Sciences, 58, M918-922.

Additional Readings

Plum, F. (1996). Neurologic problems associated with aging. In J.C. Bennett & F. Plum (Eds.), Cecil textbook of medicine (pp. 16-17). Philadelphia: W.B. Saunders Company.

Julie Prettyman, RN, CCRC, is a Director of Clinical Research, Lawrenceville Urology Clinical Research, Lawrenceville, NJ.

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