The Right Route: The Site of Injection Matters

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Case 1
A 46 year old morbidly obese diabetic patient arrives in your ED with hypoglycemia, altered mental status and diaphoresis, and no peripheral venous access. You order IM Glucagon until IV access can be established and an amp of D50 can be given. The nurse gives the IM injection using the dorsogluteal site, and attempts at IV access continue. After 15 minutes, there is no marked change in the patient’s condition and an IO is placed to treat hypoglycemia. Why didn’t the Glucagon help?

Case 2
A 55 year old woman with metastatic cancer, on an IV Dilaudid pump, is brought to the ED by her son for management of increasing pain that is not managed with the continuous infusion and intermittent boluses of 1 mg Dilaudid. She is grim and quiet and you can see that she is in severe pain. However, she is extremely cachectic, with no IV access, no fat and very little muscle mass. You cringe at the thought of a painful IM injection. Your nurse suggests a 2 mg dose of subq Dilaudid. You appreciate the recommendation and write the order.

While in most EDs, nurses perform injections, in wilderness, prehospital, and disaster situations, physicians or paramedics must provide injections, so it is important to understand the anatomic principles of injection. Currently the most commonly used sites for the rapid delivery of rescue medications are the IV, IM, and subcutaneous sites. These routes result in differences in drug absorption, onset of action, and duration of action of rescue medications.


IV drug administration achieves high plasma concentrations rapidly in plasma and tissues. Muscles are very vascular structures, and IM absorption occurs by drug diffusion from interstitial fluid and capillary membranes into plasma, and so onset of action is longer than IV injection. IM absorption depends upon blood flow. For example, if insulin is injected into the thigh, jogging right away may cause a precipitous drop in blood sugar because blood flow is increased in the thigh with running. Local heat and massage can also increase blood flow and enhance IM absorption. The rate of absorption in the gluteus is slower than injection into the deltoid.

The main components of subcutaneous tissue are fat lobules and loose collagenous connective tissue. Medications injected subcutaneously must diffuse through the subcutaneous tissue to reach capillaries, and then be absorbed into the systemic circulation. Consequently, onset of action is longer with sq than with IM administration. In addition, lipose-rich subcutaneous tissue is not vascular, so drug absorption is further prolonged if medication is delivered mostly into adipose tissue, and the drug can accumulate in adipose tissue, especially with repetitive dosing. Rate of absorption is slower in females than in males because females have more fat. Lipophilic agents, such as fentanyl, can also accumulate in adipose tissue, affecting the anticipated onset of action and duration of the drug. While fentanyl is highly lipophilic, hydromorphone is intermediate, and morphine is hydrophilic.

Some rescue medications have significant delays in peak plasma concentrations between the two routes. Most notably, epinephrine onset of action varies from between 8 minutes to 34 minutes when given SC as opposed to with an IM auto injector. To prevent these delays and maximize the chances of an injection hitting its intramuscular target, select the appropriate location and needle length to do the job.

Selecting the Most Appropriate Site 
Choosing one of the approved locations and needle length for an IM injection seems arbitrary, but there is literature available to assist in decision-making. One of the most popular location choices for IM injections is the dorsogluteal site. This site is located above the line between the greater trochanter and the posterior superior iliac crest, with the injection to be given in the superior lateral position to that line. One of the inherent flaws with this injection site is its proximity to the sciatic nerve and large blood vessels, as well as the amount of subcutaneous tissue most human beings have at this location. In one study, based on CT images of patients post dorsolgluteal injections of prescribed medications, only 32% of patients were found to have intramuscular injections where 68% were subcutaneous. When looking at needle length, patients who had a body mass index (BMI) of over 24.9kg/m2, the mean subcutaneous tissue depth at the dorsogluteal site was 34.5 mm for overweight adults, 40.2mm for obese adult and 51.4mm for extremely obese adults. At these depths, 98% of these women and 37% of these men would end up receiving subcutaneous injections using conventional 1.5 inch needles. Despite this and other literature to support the fact that the dorsoglutial site should no longer routinely be used for IM injections, one study found that 71% of Canadian nurses used the dorsogluteal site compared to the 14% that used the more effective ventrogluteal site, with studies ranging as high as 99% toward preferring the dorsogluteal.

The ventrogluteal site, rectus femoris and vastus lateralis location are the preferred location for large volume deep muscle IM injections. These injection locations allow for a high degree of safety, reliability and accessibility when a patient is lying supine, prone or in side lying position. The sites can support large volumes from 2 to 5mL and absorb quickly into the bloodstream. The deltoid is a small volume muscle and has longer peak plasma concentration times for drugs like epinephrine.


Selecting the Right Needle 
Remember the “5 Rights”: right patient, right drug, right route, right dose, and right frequency. While most of the “rights” come instinctively, become familiar with the different needles and volumes for proper administration (see table 2).

table2a table2b

Consider the patient’s weight before selecting a route of injection and needle size. Women with a BMI greater than 25 need a longer needle size for IM injections due to a thicker SQ tissue when compared to men. Remember that 83% of overweight and obese patients do not receive IM injections correctly, and injections are likely to be SQ due to inappropriate needle size. However, the absorption of SQ injections, whether intended or not intended, can be improved by applying heat or massage.

Opioids can be given IM, IV, and SQ, but which is preferred? While IV opioids have the fastest onset times (Morphine: 5 – 10 minutes), IM and SQ routes are options when IV access is a barrier to administration. IM injections have more desirable peak effect times when compared to SQ injections (Morphine onset IM: 30 – 90 minutes, SQ: 50 – 90 minutes), but are less desirable given risk of hematoma and increased site pain. When comparing SQ to IM injections, most patients preferred SQ. Most injectable opioids are marketed for IV and IM injections, but the following medications are commonly used SQ: fentanyl, morphine, and hydromorphone.

Epinephrine (Adrenalin)
Administration of this drug needs more knowledge than meets the eye. There are 3 studied routes for epinephrine administration: IM in the deltoid muscle, SQ in the upper arm, and IM in the lateral thigh. IM epinephrine administered in the lateral thigh using an autoinjector has the fastest increase in serum epinephrine compare to SQ administration. So, IM epinephrine into the lateral thigh is the preferred route of administration. However, this information cannot be explicitly extrapolated to a syringe used subcutaneously in the upper arm or an intramuscular injection in the deltoid muscle. Additionally, the effects of obesity and other absorption anomalies are not clear. While this data can be left up to interpretation, IM use of epinephrine is the first line especially when utilizing auto injectors.


Subcutaneous route of administration is a mainstay for insulin. However, IV administration of regular insulin is a go-to agent for hyperkalemia and DKA. The two routes have drastic differences in pharmacokinetics as shown below (Table 3):


The IV route properties allow it to be the desirable route when treating hyperkalemia given the faster onset allowing for quicker movement of potassium intracellularly. Subcutaneous dosing produces gentler effects on glucose or electrolytes. IV insulin may be ideal for a patient on the threshold of DKA, but not yet ready for an insulin drip. While there are many formulations of insulin, only insulin regular has been studied intravenously.

With IV, SQ, and IM routes available, become familiar with the indications and adverse effects of glucagon therapy. Hypoglycemia treatment is the backbone of glucagon use, but do not forget beta blocker overdose and gastrointestinal diagnostic aids (Table 4).


While each route has variable times of onset, peak effects are similar among the 3 groups. The IV route is generally retained for beta blocker overdose and hypoglycemia. Doses greater than 1 mg IV are likely to induce a strong emetic response. IM and SQ dosing are more often utilized for patient comfort.

Rapid Sequence Intubation (RSI)
What if you are racing between a patient’s IV access and airway? There are a 2 agents approved for intramuscular use in intubation: ketamine and succinylcholine. The dosing and pharmacokinetic differences are noted. (Tables 5 and 6).

table5 table6

While IM routes may provide quicker access to medications, the onset/durations are not desirable. A question to ask yourself would be whether you can get intravenous access before the onset of the IM medications.

Discussing the Facts 
By understanding the fundamentals of rescue medications and best practice of administration, a discussion with your nursing team will ensure that your patients will receive the greatest benefit from the medications you prescribe. With the high variability in absorption and efficacy based on route and location, decisions your nursing team makes after the order is written can sometimes be as important as the order itself.

Case 1 Conclusion
No surprise that glucagon was not effective in your presumptive timeline. Morbid obesity, likely an injection into fatty tissue into the dorsogluteal site, means you didn’t have enough time for the glucagon to be effective.

Case 2 Conclusion
Patient received relief with subq administration within about 45 minutes, longer than you anticipated with IV administration. However, at 1 hour, you were ready to send the patient home. “Wait!” said the nurse, “you need to watch that patient for respiratory distress for 2 hours, not just one! Don’t you realize the duration of action in a sq injection could be up to 2 hours?” Gulp. Observation was continued for 2 hours, during which the patient remained comfortable, and then could be safetly discharged. was continued for 2 hours, during which the patient remained comfortable, and then could be safetly discharged.


Tim Valeriote, RN, BSN, BSC, CEN is a senior member of the Emergency Department nursing team at UNC Hospitals.

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