Bolus dose vasopressors
Hypotension is a feature of many conditions affecting critically unwell patients in the emergency department. Foremost amongst these is septic shock, which we have looked at in a number of podcasts over the last few months; early use of vasopressors, in particular noradrenaline (NA) via infusion, improves outcomes in this setting. However, vasopressor infusions take time to mix and central venous access may not be immediately available. But what about the use of bolus (‘push-dose’) vasopressors when hypotension is transient or predictable?
Lets think of a couple of situations where hypotension may be a consequence of procedures we do frequently in the ED. For example, procedural sedation and RSI. In these situations use of peripheral, push-dose vasopressors may be required to bolster the blood pressure in the short-term. We’ve already discussed the whole issue of safety around peripheral vasopressors in a previous podcast (get it here).
In this episode we are going to look at what the literature says about which agent to use and also briefly mention how to draw up and administer them. As a reminder, vasoactive agents include the following:
- Inotropes (improve cardiac contractility via beta adrenergic effects): adrenaline, dobutamine
- Vasopressors (cause vasoconstriction via alpha adrenergic effects): phenylephrine, NA, metaraminol, ephedrine
- Chronotropes (increase heart rate via beta one adrenergic effects): isoprenaline
|alpha1 (α1R) Vasoconstriction, inotropy||beta1 (β1R) Inotropy, chronotropy||beta2 (β2R) Inotropy, bronchodilation, vasodilation|
|Phenylephrine & metaraminol||++++|
The most commonly used vasopressors used in bolus dose are metaraminol, phenylephrine, and ephedrine. Noradrenaline and adrenaline can be used but are generally less common in push-dose – probably because they have a much larger effect on cardiac output than the other agents. If hypotension secondary to vasodilation is the primary problem (i.e. cardiac output is reasonable), we need alpha agonism, not beta.
In routine UK anaesthetic practice, metaraminol and ephedrine are typically used to treat hypotension in the peri-intubatinon period with phenylephrine being reserved largely for obstetric practice. As you can imagine, a lot of what we know about vasopressor use comes from the anaesthetics and critical care worlds. As such, trials specific to emergency medicine are limited and not necessarily directly transferable but here’s what we’ve found.
In a study published in 2010 by Gunda et al, they compared push-dose phenylephrine (a pure alpha agonist) versus ephedrine (a synthetic alpha and beta agonist) for hypotension resulting from spinal anaesthesia – not your typical EM patient! One hundred healthy (ASA I/II) women undergoing elective cesarean section were randomised to either phenylephrine or ephedrine. The study demonstrated no significant differences in systolic and diastolic BP between the groups whilst the incidence of nausea and vomiting and tachycardia were significantly higher amongst the ephedrine group.
In a more recent RCT published in 2012, Doherty et al randomised patients to receive either infusion or bolus regimen of phenylephrine if they developed any degree of hypotension from baseline. They found no difference between the two treatment arms for the primary outcome measure of cardiac output and secondary outcome of uncontrolled hypotension however, the infusion group received significantly more phenylephrine (about twice as much).
In another study of women undergoing spinal anaesthesia, metaraminol, phenylephrine and ephedrine were compared directly. Bhardwaj et al found the mean systolic blood pressure to be similar amongst each three. The incidence of reactive hypertension was greater with metaraminol use but there were no differences in the number of boluses required between each group. There were no significant differences in the incidence of hypotension and the incidence of low systolic BP <80% of target was comparable. No patient required study withdrawal for non-response to treatment. The group did find that mean heart rate was significantly higher with ephedrine use than for metaraminol or phenylephrine but there were no episodes of bradycardia requiring treatment.
At last, in 2015, we see the first paper looking at push-dose vasopressor use in the ED! Panchal et al again used phenylephrine to look at the incidence of peri-intubation hypotension. In this retrospective study of 119 patients undergoing intubation in the ED, push-dose phenylephrine was shown to significantly increase systolic and diastolic BP with no change in heart rate. They did conclude that phenylephrine use was not systematic with many hypotensive patients not receiving treatment. They suggested that further studies are warranted to elucidate better working practices. In routine anaesthetic practice in the UK push dose metaraminol is frequently used during the peri-intubation period with a typical bolus dolus of 0.5mg. This can be repeated in 3-5 minutes if required.
In a study published in 1999, Critchley et al undertook a small study in 20 patients undergoing spinal anaesthesia to assess the optimum dose of metaraminol required to treat hypotension defined as a fall of 25% from systolic BP. Bolus doses of between 0.25mg to 1.0mg per were administered. The study demonstrated that the median dosage to produce a 25% increase in sBP (i.e. back to baseline) was 0.5mg. Individual patient responses varied significantly (10th to 90th centiles – 0.23mg to 0.8mg) and they concluded that the optimum dose was 0.25mg increasing to 0.5mg if necessary to treat hypotension resulting from spinal anaesthesia.
So, what’s the take home?
Push-dose pressors are safe to use in the short term when administered peripherally. Common agents used in the UK, i.e. metaraminol, ephedrine and phenylephrine, are comparable in their ability to raise systolic blood pressure. Side-effects may be more marked with ephedrine and at least in my practice, ephedrine takes a little longer to work. Key considerations when using an agent are to ensure correct dilution and mixing.
Try to become familiar with a specific agent so you have confidence with it. For information about how to draw up some of these agents, see Scott Weingart’s excellent post.
- For metaraminol: Mixing: take a 20ml syringe with 19ml of 0.9% saline. Add to it 1ml of metaraminol (vial contains metaraminol 10mg/ml). This gives you 20mls of 0.5mg/ml metaraminol. Dose: 1ml every 3-5 minutes depending on response. Remember to flush your line!
- Senz A, Nunnink L. Review article: inotrope and vasopressor use in the emergency department. Emerg Med Australas. 2009 Oct;21(5):342-51
- Neerja Bhardwaj, Kajal Jain, Suman Arora, and Neerja Bharti. 2013. A comparison of three vasopressors for tight control of maternal blood pressure during cesarean section under spinal anesthesia: Effect on maternal and fetal outcome. J Anaesthesiol Clin Pharmacol. 2013 Jan-Mar; 29(1): 26–31
- Doherty A, Ohashi Y, Downey K, Carvalho JC. 2012. Phenylephrine infusion versus bolus regimens during cesarean delivery under spinal anesthesia: a double-blind randomized clinical trial to assess hemodynamic changes. Anesth Analg. 2012 Dec;115(6):1343-50
- Panchal AR, Satyanarayan A, Bahadir JD, Hays D, Mosier J. Efficacy of Bolus-dose Phenylephrine for Peri-intubation Hypotension. J Emerg Med. 2015 Oct;49(4):488-94.
- Critchley LA1, Karmakar MK, Cheng JH, Critchley JA. 1999. A study to determine the optimum dose of metaraminol required to increase blood pressure by 25% during subarachnoid anaesthesia. Anaesth Intensive Care. Apr;27(2):170-4