You are working in the paediatric emergency department overnight, and the resus nurses are checking the emergency drugs during their daily checks. The department is quiet, and one of the newly qualified nurses asks you to explain why there are so many different concentrations of adrenaline and how they work. On his last shift, he noticed a different dose for croup vs. cardiac arrest.
So, what is adrenaline, and how does it work?
Adrenaline, an endogenous catecholamine produced by the adrenal medulla, exerts its effects on both alpha- and beta-adrenergic receptors in a dose-dependent manner, triggering the well-known sympathomimetic ‘fight or flight’ response to stress. Primarily through cAMP, it targets beta-1 receptors cardiac muscle cells, thereby increasing heart rate and contractility.
At higher doses, adrenaline acts on alpha-1 and alpha-2 receptors in blood vessels, causing vasoconstriction, which increases systemic vascular resistance and enhances blood return to the heart and lungs. At lower doses, adrenaline exhibits some beta-2 agonist activity, leading to peripheral vasodilation and bronchodilation. When endogenously overproduced, e.g. by a secretory adrenal medullary tumour like phaeochromocytomas, symptoms and signs include anxiety, palpitations, weight loss, tachycardia and hypertension.
Adrenaline receptors – table from https://dontforgetthebubbles.com/picu-inotropes-and-vasopressors/
| Dose mcg/kg/min | α1 | α2 | β1 | β2 | Clinical effect |
| 0-0.05 | ++ | ++ | ↑ HR, SV, CO | ||
| 0.05-0.10 | +++ | ↑ HR, SV, CO | |||
| 0.10-0.20 | +++ | +++ | +++ | ↑ HR, SV, SVR ( ↓CO) |
Side effects include increasing myocardial oxygen requirement, tachyarrhythmias, worsening diastolic function, tachyphylaxis, hyperglycaemia, and an increase in lactate.
In daily practice, we use exogenous adrenaline, making it crucial to understand its various indications and appropriate dosages to ensure its safe prescription and use.
Indications
Cardiopulmonary resuscitation
The Resuscitation Council 2021 guidelines, which are covered in this DTFB article, state that every child with cardiorespiratory arrest should have the rhythm assessed as soon as possible following the initiation of BLS.
If the infant or child is in a non-shockable rhythm (bradycardia, asystole, PEA), adrenaline should be administered as soon as possible, ideally within the first three minutes of identifying the non-shockable cardiac arrest. It should be delivered intravenously, or if intravenous access is unavailable, via the intraosseous route. Subsequently, adrenaline should be administered every 3-5 minutes or every other cycle.
In cases of shockable rhythm (pulseless ventricular tachycardia or ventricular fibrillation), which occur in only 4-8% of all paediatric cardiac arrests, adrenaline remains crucial. For infants or children in a shockable rhythm, cardiac defibrillation takes precedence. If three shocks fail to achieve ROSC, following the third shock and after cardiac compressions have resumed, IV adrenaline should be administered (alongside IV amiodarone over 20 min). Thereafter, IV adrenaline should be given every 3-5 minutes (every other cycle) until ROSC.
The dose for both sides of the algorithm is the same:
IV adrenaline 10 micrograms/kg equals 0.1ml/kg of 1 in 10,000 solution.
Mini-jets of adrenaline (1 in 10,000) are available to dose in an arrest situation quickly. For example, for a 24-kg child, you will need 240 micrograms of adrenaline 1 in 10,000. If 0.1 ml contains 10 micrograms, each dose of adrenaline will be 2.4 ml (0.1mls/kg of 1 in 100,00).
Anaphylaxis
Once the diagnosis of anaphylaxis is made, adrenaline is administered intramuscularly at a concentration of 1mg/1 ml, giving 1:1000 adrenaline. If no response is seen after 5 minutes, a repeat dose can be given IM.
Dosing as per the Resus Council guidelines:
Adult and child >12 years: 500 micrograms IM (0.5 mL)
Child 6–12 years: 300 micrograms IM (0.3 mL)
Child 6 months to 6 years: 150 micrograms IM (0.15 mL)
Child <6 months: 100–150 micrograms IM (0.1–0.15 mL)
In expert anaesthetic or intensivist hands, intravenous adrenaline can be used to manage severe anaphylaxis. Further information can be found on the Resus Council algorithm.
The newly qualified nurse explains that they now understand the different dosages but asks you to explain why we have different strengths of adrenaline, as it all seems quite confusing.
Understanding this is crucial, as it is easy to mistakenly grab the wrong concentration of emergency drugs like adrenaline during a crisis, which can lead to significant errors!
Adrenaline needs to be diluted because it is an extremely potent drug, meaning very little volume is required to cause an effect.
Consider the volumes required. If you get stung by a bee and develop anaphylaxis, you might just prefer an IM injection of 0.5ml of 1:1000 adrenaline (= 0.5mg = 500 micrograms) rather than 5ml of 1:10,000 solution…
Acute hypotension
At this point, the red phone in the emergency department rings.
The pre-alert is for a 2-year-old child with an estimated weight of 12kg.
They have a five-day history of fever and cough and have become increasingly lethargic and mottled overnight. They are tachycardic with a capillary refill time of 6 seconds, and the crew are struggling to get a blood pressure despite 30ml/kg intravenous fluid resuscitation.
The crew are 25 minutes away from the ED.
One of the experienced resus nurses suggests that they prepare a peripheral adrenaline infusion, and you request some push doses of dilute adrenaline to be drawn up.
Resus Council guidelines state that adrenaline (alongside noradrenaline) should be used as first-line vasoactive drugs in the setting of circulatory failure leading to acute hypotension. A continuous intravenous infusion of adrenaline should be used in fluid-resistant shock, and anyone who is an APLS provider needs to feel comfortable initiating this management via either peripheral or central access. It is important to remember that the concentration of adrenaline infusion differs depending on whether peripheral or central adrenaline is being used.
‘Push dose’ of dilute adrenaline is now being used more widely. This refers to small aliquots of diluted adrenaline which can be drawn up and administered quickly. This has the benefit of rapid response to the peri-arrest crashing child (where making up an adrenaline infusion would take too long), or in predictably brief hypotensive episodes such in response to induction of anaesthesia. Push dose adrenaline can be given to effect, usually every 30 seconds to 10 minutes, and is administered peripherally or centrally. Don’t forget to think about the dead space in your cannula and extension or giving set – if your push dose hasn’t had any effect, it may still be sitting in your line, especially in a smaller patient!
The newly qualified nurse asks you to help them make up the push dose of adrenaline, as the resus nurse is busy preparing the adrenaline infusion.
You explain that you need to use a stepwise approach to make up the push dose of dilute adrenaline.
Take 1 ml of 1 in 10,000 adrenaline. This gives 0.1mg/ml of adrenaline, or 100 micrograms/ml.
Dilute this with 9 ml of 0.9% saline to make up a 10 ml syringe.
This gives an adrenaline concentration of 1 in 100,000, which is 10 micrograms/ml.
You then need to calculate the dose of push dose adrenaline, which is 0.1ml/kg of 1 in 100,000 adrenaline, or 1 microgram/kg. This is to a maximum of 2ml.
For our 12kg child, we need to prepare 0.1ml/kg = 1.2ml of 1 in 100,000 adrenaline. This is equivalent to 12 micrograms of adrenaline per push dose.
Other indications
Stridor
Nebulised adrenaline is used to manage acute upper airway obstruction, such as in severe croup or post-extubation stridor.
A 1 in 1000 adrenaline solution (1mg/ml) is administered at a dose of 0.4mg/kg (up to a maximum of 5mg) with careful monitoring.
The effects last for at least one hour, providing a window for corticosteroids to take effect. However, once the nebulised adrenaline wears off, monitor for rebound stridor and recurrence of severe respiratory distress. As with many paediatric medications, adrenaline is not licensed for this indication.
Alongside local anaesthetic
Finally, adrenaline can be used alongside a local anaesthetic to delay absorption, prolong the anaesthetic effect, and improve safety by reducing toxicity. Of course, an important contraindication is to avoid digits or appendages due to the risk of ischaemic necrosis.
Table of Use
| Indication | Route | Concentration | Dose |
| Cardiac arrest | IV/IO | 1 in 10,000 (0.1mg/ml) | 0.1ml/kg = 10mcg/kg |
| Anaphylaxis | IM | 1 in 1000 (1mg/ml) | Adult and child >12 years: 500 micrograms IM (0.5 mL) Child 6–12 years: 300 micrograms IM (0.3 mL) Child 6 months to 6 years: 150 micrograms IM (0.15 mL) Child <6 months: 100–150 micrograms IM (0.1–0.15 mL) |
| Acute hypotension – adrenaline infusion | IV | Peripheral: 1mg in 50ml Central: 1-8mg in 50ml (weight-dependent) | 0.01- 0.2 microgram/kg/min |
| Acute hypotension – adrenaline bolus push dose | IV | 1 in 1000 (1mg/ml) | 0.1ml/kg = 1mcg/kg |
| Stridor | Neb | 1 in 1000 (1mg/ml) | 0.4ml/kg = 400 mcg/kg to maximum of 5ml = 5mg |
Literature review
Harley A, George S, Phillips N, King M, Long D, Keijzers G, Lister P, Raman S, Bellomo R, Gibbons K, Schlapbach LJ; Resuscitation in Paediatric Sepsis Randomised Controlled Pilot Platform Study in the Emergency Department (RESPOND ED) Study Group. Resuscitation With Early Adrenaline Infusion for Children With Septic Shock: A Randomised Pilot Trial. Pediatr Crit Care Med. 2024 Feb 1;25(2):106-117. doi: 10.1097/PCC.0000000000003351. PMID: 38240535.
An Australian study group based in four Queensland paediatric emergency departments published a randomised controlled pilot trial in 2024. This study investigated the use of early adrenaline infusion versus extended fluid resuscitation in children with septic shock. It studied children and young people between 28 days and 18 years old with clinician-defined septic shock after the minimum of 20ml/kg fluid resuscitation in the preceding four hours before randomisation.
Patients were recruited via block randomisation, and the study was non-blinded with full written consent. In the intervention arm, early adrenaline infusion was initiated immediately after the first 20ml/kg fluid resuscitation, compared to standard care fluid resuscitation defined as 40 to 60 mL/kg fluid resuscitation before starting inotropes. As a pilot study, the primary outcomes focused on the feasibility and safety of the study. Exploratory clinical outcomes included survival without organ dysfunction at 28 days, length of hospital stay and duration of PICU admission.
Over two years (2019-2021), over 600 children were screened across the four EDs, with 58 eligible patients found. This left an intention-to-treat analysis of 40 enrolled patients. After the initial 20ml/kg fluid resuscitation, seventeen (43%) were enrolled in the early adrenaline intervention, and 23 were enrolled in standard care.
Early adrenaline infusion use was associated with more and earlier inotrope use and less fluid resuscitation in the first 24 hours. This approach did not lead to a rise in adverse events, longer PICU admissions, or longer hospital stays. Limitations of this feasibility study include a non-blinded design, a small patient cohort with low acuity (no mortality), and the exclusive focus on adrenaline initiation rather than both adrenaline and noradrenaline.
Notably, among four of the patients randomised to early inotropes (25%), clinicians decided not to start, which could reflect ongoing reluctance in paediatrics to initiate inotropes in the emergency department with increased familiarity surrounding fluid resuscitation.
Reiter PD, Roth J, Wathen B, LaVelle J, Ridall LA. Low-Dose Epinephrine Boluses for Acute Hypotension in the PICU. Pediatr Crit Care Med. 2018 Apr;19(4):281-286. doi: 10.1097/PCC.0000000000001448. PMID: 29319635.
A 2018 study investigated the use of low dose ‘push dose’ adrenaline in critically ill children during a peri-arrest episode or acute hypotensive episode within one American tertiary hospital PICU setting.
The intervention was a low-dose bolus of adrenaline (less than 5 micrograms/kg), and the primary outcome was a change in heart rate and mean arterial blood pressure (MAP) from baseline. Secondary outcomes included the number of children who went on to be managed for cardiac arrest and overall survival from PICU.
The study analysed 19 patients over one year, with adrenaline administration occurring 63 times during 24 resuscitation episodes. The most common causes for PICU admission were septic shock (27%), respiratory failure (21%), trauma (12%) and oncology (11%). The mean dose of adrenaline given was 1.3 ± 1.1 mcg/kg, with a median number of doses per patient of two.
Fourteen of the 24 events (58%) included the provision of multiple doses of bolus adrenaline. If more than one dose was provided, the median dosing interval was 6 minutes. Heart rate changed from 130 ± 41 to 150 ± 33 beats/min (p < 0.05), and mean arterial blood pressure changed from 51 ± 17 to 75 ± 27 mm Hg (p < 0.001). 66% of doses resulted in up to 100% increase in MAP, and 21% resulted in greater than 100% MAP increase.
Overall, there was variability in blood pressure following adrenaline administration, with the most significant increase seen in children under two years old. Although a small study, this suggests that push dose adrenaline can be used to increase HR and MAP in critically ill children during acute hypotension. However, the number of doses required reminds us that it is only a temporising measure, and we need to concentrate on treating the underlying cause of hypotension.
Conclusions
The child arrives at the ED peripherally shut down, with no response to further fluid resuscitation.
They are started on a peripheral adrenaline infusion and require two doses of push dose adrenaline with good effect.
They are admitted to the local PICU with a diagnosis of sepsis secondary to Group A Streptococcus and, after a two-week PICU admission, are discharged to the ward.
During the next resus call with a septic child, you overhear the newly qualified nurse suggest making up some push doses of adrenaline. The consultant in charge agrees.
The three final take-home messages from this case-based discussion on the use of adrenaline include:
Familiarise yourself with the various strengths of adrenaline available and how they are used in different emergency scenarios.
Think early about starting an adrenaline infusion in hypotensive patients who do not respond to fluid resuscitation. Begin with a sufficient dose, such as 0.1mcg/kg/min, to ensure it effectively reaches the patient and has the desired impact.
When managing a peri-arrest hypotensive patient, consider push dose(s) of dilute adrenaline for temporarily stabilisation, but ensure you also treat the root cause of hypotension.Â
About PICSTAR
PICSTAR is a trainee-led research network open to all doctors, nurses and allied health trainees within Paediatric Intensive Care. We are the trainee arm of the Paediatric Critical Care Society – Study Group (PCCS-SG) and work with them on research, audit and service evaluation.
If you would like to join PICSTAR and get involved in projects, have ideas you would like to propose or get advice/mentorship via PCCS-SG, don’t hesitate to contact us at picstar.network@gmail.com. See their website for more: https://pccsociety.uk/research/picstar/
References
https://dontforgetthebubbles.com/picu-inotropes-and-vasopressors/
https://www.resus.org.uk/sites/default/files/2021-04/Anaphylaxis%20algorithm%202021.pdf
https://bnf.nice.org.uk/drugs/adrenaline-epinephrine/
https://www.paediatricemergencies.com/peripheral-vasoactive-drugs-in-kids/
Zhang L, Sanguebsche LS. The safety of nebulization with 3 to 5 ml of adrenaline (1:1000) in children: an evidence based review. 2005. In: Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK71338/
Harley A, George S, Phillips N, King M, Long D, Keijzers G, Lister P, Raman S, Bellomo R, Gibbons K, Schlapbach LJ; Resuscitation in Paediatric Sepsis Randomised Controlled Pilot Platform Study in the Emergency Department (RESPOND ED) Study Group. Resuscitation With Early Adrenaline Infusion for Children With Septic Shock: A Randomised Pilot Trial. Pediatr Crit Care Med. 2024 Feb 1;25(2):106-117. doi: 10.1097/PCC.0000000000003351. PMID: 38240535.
Reiter PD, Roth J, Wathen B, LaVelle J, Ridall LA. Low-Dose Epinephrine Boluses for Acute Hypotension in the PICU. Pediatr Crit Care Med. 2018 Apr;19(4):281-286. doi: 10.1097/PCC.0000000000001448. PMID: 29319635.
