What data is available supporting (or refuting) the use of ephedrine subcutaneously?

Comment by InpharmD Researcher

Published literature are scarce and dated; one identified study (Table 1) observed prophylactic ephedrine to reduce incidence of hypotension in older adults following epidural blockade. An Australian package insert for ephedrine describes the agent to be rapidly absorbed after subcutaneous administration, with duration of response approximately 1 hour after 25-50 mg; however, U.S. labels do not reflect this pharmacokinetic property, and thus caution is warranted.
Relevant Prescribing Information

Pharmacokinetics [1]
Ephedrine is rapidly absorbed after intramuscular or subcutaneous administration. The onset of action after intramuscular administration is 10 to 20 minutes, and the duration of pressor and cardiac responses to ephedrine is 1 hour after intravenous administration of 10 to 25 mg or intramuscular or subcutaneous administration of 25 to 50 mg.

Relevant Prescribing Information References: [1] DBL™ Ephedrine Sulfate Injection. Prescribing information. Hospira Australia Pty Ltd.; 2019.
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What data is available supporting (or refuting) the use of ephedrine subcutaneously?

Level of evidence

D - Case reports or unreliable data  Read more→


Please see Table 1 for your response.

The Use of Ephedrine for Prevention of Arterial Hypotension during Epidural Blockade
Design

Comparative study

N= 48
Objective To elucidate the effect of ephedrine on the central circulation in middle-aged and elderly patients receiving high epidural blockade
Study Groups

Bupivacaine adrenaline (n= 8)

Bupivacaine adrenaline with ephedrine (n= 8)

Etidocaine adrenaline (n= 8)

Etidocaine adrenaline with ephedrine (n= 8)

Etidocaine plain (n= 8)

Etidocaine plain with ephedrine (n= 8)
Inclusion Criteria Patients aged 44-74 years scheduled for surgery on the lower abdomen or lower limbs
Exclusion Criteria Not specified
Methods Patients received subcutaneous premedication with ephedrine or no ephedrine before epidural blockade. Epidural blockade was performed using bupivacaine 0.5% with adrenaline or etidocaine 1% with or without adrenaline. Hemodynamic parameters were measured, including arterial blood pressure, heart rate, cardiac output, and pulmonary arterial pressures. Stroke volume, left ventricular minute work, and total peripheral resistance were calculated.
Duration Not specified
Outcome Measures

Primary: Changes in arterial blood pressure, heart rate, cardiac output, and pulmonary arterial pressures

Secondary: Stroke volume, left ventricular minute work, total peripheral resistance
Baseline Characteristics   Bupivacaine adrenaline (n= 8) Bupivacaine adrenaline with ephedrine (n= 8) Etidocaine adrenaline (n= 8) Etidocaine adrenaline with ephedrine (n= 8) Etidocaine plain (n= 8) Etidocaine plain with ephedrine (n= 8)
Age, years 57.6 ± 9.8 59.6 ± 10.7 62.3 ± 8.2 64.5 ± 7.6 61.2 ± 8.0 61.4 ± 10.1
Height, cm 175.6 ± 10.7 178.1 ± 6.8 175.1 ± 9.3 177.1 ± 6.8 175.4 ± 6.9 170.8 ± 7.1
Body weight, kg 81.6 ± 16.1 79.9 ± 14.3 77.3 ± 15.6 81.1 ± 8.4 76.3 ± 8.2 71.8 ± 5.9
Results   Bupivacaine adrenaline (n= 8) Bupivacaine adrenaline with ephedrine (n= 8) Etidocaine adrenaline (n= 8) Etidocaine adrenaline with ephedrine (n= 8) Etidocaine plain (n= 8) Etidocaine plain with ephedrine (n= 8)
Mean arterial blood pressure change, mmHg -28.3 ± 16.7 -12.2 ± 17.0 -28.7 ± 16.7 0.9 ± 18.7 -24.0 ± 19.2 -16.0 ± 13.0
Heart rate change, beats/min 3.1 ± 10.9 1.3 ± 11.8 4.1 ± 7.6 0.8 ± 1.0 -4.4 ± 4.0 0.5 ± 0.5
Cardiac output change, L/min 0.9 ± 1.0 0.7 ± 1.3 1.1 ± 1.0 0.6 ± 1.2 -0.4 ± 0.5 0.6 ± 0.4
Adverse Events Not specified
Study Author Conclusions Subcutaneous premedication with ephedrine prevents hypotension following high epidural blockade and protects against extreme bradycardia. Ephedrine slightly stimulates cardiac output when adrenaline is not included in the local anesthetic solution. It is a suitable supplementary premedication before high epidural analgesia in elderly patients.
Critique The study provides valuable insights into the use of ephedrine for preventing hypotension during epidural blockade. However, the uneven distribution of patients with cardiac conditions across groups may affect the generalizability of the results. Additionally, the study does not specify the duration of follow-up, which could impact the understanding of long-term effects.

 

Table 1 References:
[2] Engberg G, Wiklund L. The use of ephedrine for prevention of arterial hypotension during epidural blockade. A study of the central circulation after subcutaneous premedication. Acta Anaesthesiol Scand Suppl. 1978;66(66):1-26. doi:10.1111/j.1399-6576.1978.tb01350.x