Evidence for the Use of Intramuscular Injections in Outpatient Practice
Am Fam Physician. 2009 Feb 15;79(4):297-300.
There are few studies comparing the outcomes of patients who are treated with oral versus intramuscular antibiotics, corticosteroids, nonsteroidal anti-inflammatory drugs, or vitamin B12. This may lead to confusion about when the intramuscular route is indicated. For example, intramuscular ceftriaxone for Neisseria gonorrhoeae infection and intramuscular penicillin G benzathine for Treponema pallidum infection are the treatments of choice. However, oral antibiotics are the treatment of choice for the outpatient treatment of pneumonia and most other outpatient bacterial infections. Oral corticosteroids are as effective as intramuscular corticosteroids and are well-tolerated by most patients. High daily doses of oral vitamin B12 with ongoing clinical surveillance appear to be as effective as intramuscular treatment. Few data support choosing intramuscular ketorolac over an oral nonsteroidal anti-inflammatory drug unless the patient is unable to tolerate an oral medication. For other indications, the intramuscular route should be considered only when the delivery of a medication must be confirmed, such as when a patient cannot tolerate an oral medication, or when compliance is uncertain.
Family physicians may choose to treat common bacterial infections, asthma, musculoskeletal pain, and vitamin B12 deficiency with medications administered through the oral or intramuscular (IM) route. Because there are few studies comparing the outcomes of patients who are treated with oral medications versus IM medications, there may be confusion about when the IM route is appropriate.
In general, IM administration may be appropriate for patients with nausea, vomiting, diarrhea, or dehydration. It may also be appropriate when the physician needs to confirm the delivery of medication, such as when a patient has failed ongoing oral treatment, or when a patient is unreliable or uncooperative. The IM route is contraindicated when the medication is erratically absorbed, when there is concern for allergic reaction, or when there is a danger to the patient. Oral medications can be easier to administer than IM injections and are equally effective for treating many conditions. Oral medications do not cause pain or compromise the skin barrier. For most patients, the evidence does not support the IM route over the oral route for antibiotics, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or vitamin B12, although IM antibiotics are indicated for some infections.
After the discovery of penicillin in the early 1940s, “the shot” became associated with a dramatic reversal of illness. Since then, injections have continued to represent a powerful medical symbol.1 Physicians and patients may perceive an injection as being more potent than standard oral treatment, and physicians may favor this route when treating a sick patient.1 However, this approach is not supported by the literature.1,2
The advantages of IM antibiotics are likely limited to situations when the delivery of a medication must be confirmed. For example, the IM route may be appropriate if a patient cannot tolerate an oral medication (e.g., because of emesis or an inability to swallow), or if the patient’s compliance is uncertain (e.g., because of forgetfulness or unwillingness to take a medication).
The American Thoracic Society and the Infectious Diseases Society of America recommend oral antibiotics for the outpatient treatment of pneumonia.3 No IM antibiotics are approved by the U.S. Food and Drug Administration or specifically recommended for acute sinusitis,4,5 and most community-acquired methicillin-resistant Staphylococcus aureus skin infections remain susceptible to oral trimethoprim/sulfamethoxazole (Bactrim, Septra) and tetracycline.6
SORT: KEY RECOMMENDATIONS FOR PRACTICE
SORT: KEY RECOMMENDATIONS FOR PRACTICE
|Clinical recommendation||Evidence rating||References|
Oral antibiotics are recommended for the outpatient treatment of pneumonia.
Intramuscular penicillin G benzathine is the recommended treatment of choice for Treponema pallidum infections, and intramuscular ceftriaxone (Rocephin) is recommended for Neisseria gonorrhoeae infections and pelvic inflammatory disease.
Intramuscular penicillin is the recommended treatment for group A beta-hemolytic streptococcal pharyngitis when the oral route cannot be used.
Intramuscular epinephrine is the recommended drug of choice for anaphylactic reactions.
Oral vitamin B12 at a dosage of 2,000 mcg per day is an effective treatment for B12 deficiency in the short term.
Intramuscular ketorolac (Toradol, no longer available for injection) is no more effective for pain syndromes than oral ibuprofen or other oral nonsteroidal anti-inflammatory agents.
A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.xml.
One systematic review found that there is no evidence that oral antibiotic therapy is less effective or slower than parenteral treatment for severe urinary tract infection in children and adults.7 Other studies have shown similar clinical effectiveness for a single dose of IM ceftriaxone (Rocephin) or 10 days of oral trimethoprim/sulfamethoxazole for urinary tract infections in febrile children.8–10 Several studies have shown that for children with otitis media, a single dose of IM ceftriaxone is no more effective in regard to rates of improvement, failure, or relapse than 10 days of oral amoxicillin, amoxicillin/clavulanate (Augmentin), or trimethoprim/sulfamethoxazole.11–13
Although IM antibiotics have not been shown to be more effective or to lead to faster recovery, they are appropriate for specific indications. For example, IM penicillin G benzathine (Bicillin L-A) is the medication of choice to treat Treponema pallidum.14 IM penicillin G benzathine alone or in combination with penicillin G procaine (Bicillin C-R) is an effective treatment for group A beta-hemolytic streptococcal pharyngitis when the oral route cannot be used.15 The Centers for Disease Control and Prevention recommends 125 mg of IM ceftriaxone to treat Neisseria gonorrhoeae infections,16 and 250 mg of IM ceftriaxone plus seven to 14 days of oral doxycycline (Vibramycin) at a dosage of 100 mg twice daily to treat pelvic inflammatory disease and epididymitis.17
The perception that IM injections are more powerful or have an added psychologic effect is unproven and is an inadequate reason to choose injection when oral antibiotics are less expensive, less painful, and have fewer serious side effects.
For acute asthma exacerbation and croup, systemic corticosteroids are the recommended treatment.18–27 Corticosteroids have been shown to lead to symptom improvement, fewer hospitalizations, and fewer return visits for both conditions.18–27 Although much of the data regarding the treatment of asthma and croup are based on emergency department and hospital encounters, there is a growing body of evidence indicating that oral treatment and IM treatment are equally effective.22–27 One study also found that oral prednisolone (Prelone) is not inferior to IM prednisolone (Predalone; brand no longer available in the United States) in treatment for exacerbations of chronic obstructive pulmonary disease.28
Multiple studies comparing IM administration of corticosteroids with oral administration have found no significant differences in outcomes between groups.20,22–26 Despite numerous trials evaluating doses, dosing frequencies, and routes of administration of various corticosteroids, there is no clear evidence for a superior formulation or administration route.20,22–26
For children who are not able to swallow pills or who refuse a bad-tasting medication, a single long-acting IM-administered corticosteroid such as dexamethasone or methylprednisolone acetate (Depo-Medrol) eliminates nonadherence.24 If the tolerability or compliance with a tapering dose of oral steroids are issues, the IM route is reasonable.23,29 However, oral corticosteroids eliminate the pain, anxiety, side effects, and costs associated with injections, and are generally well-tolerated by patients of all ages.22,25,26
Some physicians believe that corticosteroids are the treatment of choice in acute anaphylaxis, although epinephrine is the recommended medication for anaphylactic reactons.30 Epinephrine is absorbed more rapidly intramuscularly than subcutaneously.30 Corticosteroids may have some benefit in decreasing the uncommon occurrence of a protracted or biphasic reaction.30 Whether delivered parenterally or orally, the effectiveness of administering corticosteroids for anaphylaxis is unclear.
Until recently, the standard treatment for vitamin B12 deficiency has been IM vitamin B12.31–35 However, because evidence indicates that patients with vitamin B12 malabsorption (intrinsic factor deficiency) absorb only 1 to 2 percent of oral vitamin B12,32–35 high-dose oral treatment has been investigated as an alternative to IM administration.31–35
Trials of oral versus IM vitamin B12 replacement therapy have found that oral vitamin B12 in high doses appears to be as effective as IM administration in the short-term.31–35 In one study, vitamin B12 was administered orally at a dosage of 2,000 mcg per day for four months.36 This resulted in a threefold increase in the level of serum vitamin B12 compared with the monthly IM injection group. Other trials using oral dosages of less than 500 mcg per day have not shown a consistent response, which confirms the need for high-dose daily therapy.37,38 There have been no long-term outcome studies evaluating the effectiveness in treating or preventing anemia.
There are several reasons to consider oral vitamin B12 administration instead of IM injection. An injection typically requires the patient to travel to a health care facility, which may be difficult for patients with disabilities and for older patients. Additionally, injections are more expensive and painful, and place health care professionals at risk of needle-stick injuries.31–35 Although large long-term trials are needed to determine whether oral vitamin B12 is as effective as IM treatment, high-dose oral vitamin B12 treatment with ongoing clinical surveillance appears to be painless, effective, safe, cost-efficient, and convenient for most patients.31–33
All NSAIDs have the same mechanism of action, regardless of the route of administration.39–41 The data do not support the practice of administering IM ketorolac (Toradol, no longer available for injection) for conditions such as migraine, gout, and musculoskeletal pain when oral NSAIDs are available and the patient can tolerate an oral medication.40–43 The few studies that have compared an oral NSAID such as ibuprofen to IM ketorolac have not demonstrated a significantly better response to the injection.40–43
Additionally, the evidence does not support the notion that IM ketorolac is more effective than oral NSAIDs for pain relief in patients with acute renal colic.44,45 Limited studies have shown that ketorolac is as effective as certain opioids for treating renal colic pain.40,41,44,45 However, data also indicate that oral NSAIDs generally offer at least equal analgesia when compared with opioids.40,44,45 No randomized, double-blind studies are available that directly compare oral NSAIDs with IM ketorolac. One study compared administration of a placebo injection to administration of a placebo oral agent and found that injections did not confer a selective placebo effect.40
The risks of administering IM ketorolac include bruising, infection, hematoma, patient discomfort, and needle-stick injury.38,39 In addition, IM administration is significantly more expensive than oral ibuprofen.39,42 Because there is no outcome-based evidence for choosing IM ketorolac over an oral NSAID, and because there are increased costs and potential hazards with injections, IM ketorolac should be reserved for patients with acute pain who are unable to tolerate oral NSAIDs.39–42
Because of the broad nature of this topic, modes of administration were limited to the IM and oral routes. Similarly, medications such as diphenhydramine (Benadryl), opioid analgesics, ondansetron (Zofran), triptans, and others were not included. Definitive guidelines for choosing the IM route or oral route are unlikely to be forthcoming. The decision-making process involves assessing the clinical picture, knowing medication indications, and learning patient preferences. With few exceptions, there are no conclusive data that support the IM route as preferable to the oral route. The assumption that an IM injection is more powerful than the oral route is not supported by available data.
1. Reeler AV. Anthropological perspectives on injections: a review. Bull World Health Organ. 2000;78(1):135–143.
2. Kienle GS, Kiene H. The powerful placebo effect: fact or fiction? J Clin Epidemiol. 1997;50(12):1311–1318.
3. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(suppl 2):S27–S72.
4. Chang EJ, Marcy SM. Intramuscular antibiotics in the treatment of pediatric upper respiratory tract infections. Am J Manag Care. 1999;5(15 suppl):S915–S922.
5. Wong DM, Blumberg DA, Lowe LG. Guidelines for the use of antibiotics in acute upper respiratory tract infections. Am Fam Physician. 2006;74(6):956–966.
6. Stevens DL, Bisno AL, Chambers HF, et al., for the Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis. 2005;41(10):1373–1406.
7. Pohl A. Modes of administration of antibiotics for symptomatic severe urinary tract infections. Cochrane Database Syst Rev. 2007;(4): CD003237.
8. Baker PC, Nelson DS, Schunk JE. The addition of ceftriaxone to oral therapy does not improve outcome in febrile children with urinary tract infections. Arch Pediatr Adolesc Med. 2001;155(2):135–139.
9. Hoberman A, Wald ER, Hickey RW, et al. Oral versus initial intravenous therapy for urinary tract infections in young febrile children. Pediatrics. 1999;104(1 pt 1):79–86.
10. Roberts KB. The AAP practice parameter on urinary tract infections in febrile infants and young children. American Academy of Pediatrics. Am Fam Physician. 2000;62(8):1815–1822.
11. Green SM, Rothrock SG. Single-dose intramuscular ceftriaxone for acute otitis media in children. Pediatrics. 1993;91(1):23–30.
12. Barnett ED, Teele DW, Klein JO, Cabral HJ, Kharasch SJ. Comparison of ceftriaxone and trimethoprim-sulfamethoxazole for acute otitis media. Greater Boston Otitis Media Study Group. Pediatrics. 1997;99(1):23–28.
13. Varsano I, Volovitz B, Horev Z, et al. Intramuscular ceftriaxone compared with oral amoxicillinclavulanate for treatment of acute otitis media in children. Eur J Pediatr. 1997;156(11):858–863.
14. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. http://www.cdc.gov/std/treatment/2-2002TG.htm. Accessed August 22, 2008.
15. Bisno AL, Gerber MA, Gwaltney JM Jr, Kaplan EL, Schwartz RH. Practice guidelines for the diagnosis and management of group A streptococcal pharyngitis. Infectious Diseases Society of America. Clin Infect Dis. 2002;35(2):113–125.
16. Centers for Disease Control and Prevention. CDC changes recommendations for gonorrhea treatment due to drug resistance. http://www.cdc.gov/media/pressrel/2007/r070412a.htm. Accessed August 22, 2008.
17. Ross J. Pelvic inflammatory disease. Clin Evid. 2006;(15):2176–2182.
18. Institute for Clinical Systems Improvement. Health care guideline: diagnosis and management of asthma. http://www.icsi.org/asthma__outpatient/asthma__diagnosis_management_of__guideline_.html. Accessed September 2, 2008.
19. U.S. Department of Health and Human Services. National Ashtma Education and Prevention Program, Expert Panel Report 3. Guidelines for the diagnosis and management of asthma. http://www.nhlbi.nih.gov/guidelines/asthma/asthsumm.pdf. Accessed August 22, 2008.
20. Dennis R, Solarte I, Fitzgerald JM. Asthma. Clin Evid. 2005;(14): 1847–1877.
21. Rowe BH, Spooner C, Ducharme FM, Bretzlaff JA, Bota GW. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2001;(1):CD002178.
22. Rowe BH, Spooner CH, Ducharme FM, Bretzlaff JA, Bota GW. Corticosteroids for preventing relapse following acute exacerbations of asthma. Cochrane Database Syst Rev. 2000;(2):CD000195.
23. Lahn M, Bijur P, Gallagher EJ. Randomized clinical trial of intramuscularvs oral methylyprednisolone in the treatment of acute asthma exacerbations following discharge from an emergency department. Chest. 2004;126(2):362–368.
24. Gries DM, Moffitt DR, Pulos E, Carter ER. A single dose of intramuscularly administered dexamethasone acetate is as effective as oral prednisone to treat asthma exacerbations in young children. J Pediatr. 2000;136(3):298–303.
25. Amir L, Hubermann H, Halevi A, Mor M, Mimouni M, Waisman Y. Oral betamethasone versus intramuscular dexamethasone for the treatment of mild to moderate viral croup: a prospective, randomized trial. Pediatr Emerg Care. 2006;22(8):541–544.
26. Rittichier KK, Ledwith CA. Outpatient treatment of moderate croup with dexamethasone: intramuscular versus oral dosing. Pediatrics. 2000;106(6):1344–1348.
27. Bjornson CL, Klassen TP, Williamson J, et al., for the Pediatric Emergency Research Canada Network. A randomized trial of a single dose of oral dexamethasone for mild croup. N Engl J Med. 2004;351(13):1306–1313.
28. de Jong YP, Uil SM, Grotjohan HP, Postma DS, Kerstjens HA, van den Berg JW. Oral or IV prednisolone in the treatment of COPD exacerbations: a randomized, conrolled, double-blind study. Chest. 2007;132(6):1741–1747.
29. Razi E, Moosavi GA. A comparative efficacy of oral prednisone with intramuscular triamcinolone in acute exacerbation of asthma. Iran J Allergy Asthma Immunol. 2006;5(1):17–22.
30. Drugs for allergic disorders. Treat Guidel Med Lett. 2007;5(60):71–80.
31. Andrès E, Federici L, Affenberger S, et al. B12 deficiency: a look beyond pernicious anemia. J Fam Pract. 2007;56(7):537–542.
32. Oh R, Brown DL. Vitamin B12 deficiency. Am Fam Physician. 2003;67(5):979–986.
33. Butler CC, Vidal-Alaball J, Cannings-John R, et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency: a systematic review of randomized controlled trials. Fam Pract. 2006;23(3):279–285.
34. Nyholm E, Turpin P, Swain D, et al. Oral vitamin B12 can change our practice. Postgrad Med J. 2003;79(930):218–220.
35. Eussen SJ, de Groot LC, Clarke R, et al. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med. 2005;165(10):1167–1172.
36. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92(4):1191–1198.
37. Lederle FA. Oral cobalamin for pernicious anemia. Medicine’s best kept secret? JAMA. 1991;265(1):94–95.
38. Rajan S, Wallace JI, Brodkin KI, Beresford SA, Allen RH, Stabler SP. Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. J Am Geriatr Soc. 2002;50(11):1789–1795.
39. Drugs for pain. Treat Guidel Med Lett. 2007;5(56):23–32.
40. Arora S, Wagner JG, Herbert M. Myth: parenteral ketorolac provides more effective analgesia than oral ibuprofen. CJEM. 2007;9(1):30–32.
41. Turturro MA, Paris PM, Seaberg DC. Intramuscular ketorolac versus oral ibuprofen in acute musculoskeletal pain. Ann Emerg Med. 1995;26(2):117–120.
42. Schwartz NA, Turturro MA, Istvan DJ, Larkin GL. Patients’ perceptions of route of nonsteroidal anti-inflammatory drug administration and its effect on analgesia. Acad Emerg Med. 2000;7(8):857–861.
43. Shrestha M, Morgan DL, Moreden JM, Singh R, Nelson M, Hayes JE. Randomized double-blind comparison of the analgesic efficacy of intramuscular ketorolac and oral indomethacin in the treatment of acute gouty arthritis. Ann Emerg Med. 1995;26(6):682–686.
44. Teichman JM. Clinial practice. Acute renal colic from ureteral calculus. N Engl J Med. 2004;350(7):684–693.
45. Holdgate A, Pollock T. Systematic review of the relative efficacy of non-steroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic [published correction appears in BMJ. 2004;329(7473):1019]. BMJ. 2004;328(7453):1401.
This is one in a series of “Clinical Pharmacology” articles coordinated by Allen F. Shaughnessy, PharmD, Tufts University Family Medicine Residency, Malden, Mass.
Copyright © 2009 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact firstname.lastname@example.org for copyright questions and/or permission requests.
Want to use this article elsewhere? Get Permissions