Overview of Medication Routes

November 16, 2020

Medications, including anesthetics, can be administered via a variety of routes. These options include oral administration, injection—including intravenous, intra-articular, intramuscular, intrathecal, and subcutaneous—rectal or vaginal administration, and inhalation or nebulization [1]. Doctors and patients may prefer different medication routes. Ultimately, the choice of anesthesia route should take into account effectiveness in reducing pain or suppressing brain activity, as well as any psychological effects on patients. 

Seeking to determine the effectiveness of various medication routes on children undergoing general anesthesia, a study by Tolksdorf et al. divided 90 patients into groups receiving oral, rectal, or nasal midazolam, according to the patient’s or guardian’s preferences. The patients were most receptive to oral administration prior to surgery, but rectal administration was most effective by a variety of measures: it induced sedation most quickly, led to more predictable sedation, and avoided the side effects of euphoria (associated with nasal administration) and nausea (associated with oral administration). This reflects a more general issue in the choice of administration routes: while patients and their families may prefer a given route, doctors are likely to find other routes more effective and predictable [2]. 

Widespread perceptions surrounding the unpleasantness of various methods may influence the anxiety felt by patients and families, thereby affecting their actual experience of a given administration route. In a survey by Seth et al. of 150 parents, 58% expressed a belief that rectal administration was the most unpleasant anesthesia option for their own children, while 19% believed intramuscular administration to be the most unpleasant. Only 11% said the same of intravenous administration, while 9% believed oral administration to be most unpleasant [3]. While these perceptions do not directly influence the measurable effectiveness of these routes, and do not necessarily reflect actual differences in patient experience, they suggest that certain medication routes may ease or exacerbate existing anxieties surrounding medical procedures. 

A large body of research comparing various injection routes suggests that different administrations may be preferable depending on the desired outcome—decreased pain, lowered BIS values, or speedy recovery. A randomized study compared the analgesic effectiveness of intra-articular, intravenous, and intramuscular routes for administering magnesium sulfate in knee arthroscopy. Intra-articular injection was associated with shorter time periods before performing knee flexions and lower scores on an injury survey—implying that both doctors and patients may find this administration route preferable. Indeed, the intra-articular group was able to perform knee flexions in a mean 180 minutes, while each other group’s mean time was between 220-230 minutes [4]. 

On the other hand, a study of 64 women undergoing cesarean sections by Fernandes et al. found no significant difference between the effects of intrathecal and intravenous delivery of clonidine on acute postoperative pain [5]. Yet another study by Kushida et al. looked at patients undergoing cesarean section procedures. It found that intrathecal fentanyl reduced BIS values significantly compared to routes that mixed intrathecal with epidural or isobaric administration [6]. 

While patients are likely to find oral routes for anesthesia delivery less intimidating than inhalation or rectal routes, other studies suggest that oral routes may be less effective, necessitating a balance between patients’ and doctors’ priorities. Within the various options for injected anesthetics, meanwhile, different routes appear preferable according to the drug and procedure at hand. 


[1] Le, J., et al. “Drug Administration – Drugs.” Merck Manuals Consumer Version, Merck Manuals, www.merckmanuals.com/home/drugs/administration-and-kinetics-of-drugs/drug-administration.  

[2] Tolksdorf, W., and C. Eick. “Rektale, orale und nasale Prämedikation mit Midazolam bei Kindern im Alter von 1-6 Jahren. Eine vergleichende klinische Untersuchung” [Rectal, oral and nasal premedication using midazolam in children aged 1-6 years. A comparative clinical study]. Der Anaesthesist, vol. 40,12 (1991): 661-7., PMID: 1781563. 

[3] Seth, N., et al. “Parental Opinions Regarding the Route of Administration of Analgesic Medication in Children.” Pediatric Anesthesia, vol. 10, no. 5, 2000, pp. 537–544., doi:10.1046/j.1460-9592.2000.00564.x.  

[4] El Sayed, M., and S. Hassan. “Different Routes of Co-Administration of Magnesium Sulphate with Spinal Anesthesia in Knee Arthroscopy: Randomized Controlled Trial.” Egyptian Journal of Anaesthesia, vol. 33, no. 3, 2017, pp. 271–276., doi:10.1016/j.egja.2017.05.001.  

[5] Fernandes, H. S., et al. “Clonidine Effect on Pain After Cesarean Delivery.” Anesthesia & Analgesia, vol. 127, no. 1, 2018, pp. 165–170., doi:10.1213/ane.0000000000003319.  

[6] Kushida, A. et al.  “Fentanyl Shows Different Effects by Administration Routes on Bispectral Index during Spinal Anesthesia in Patients Undergoing Cesarean Section.” Masui: The Japanese Journal of Anesthesiology, vol. 55, no. 11, 31 Oct. 2006, pp. 1393–1397., PMID: 17131892.