Noradrenaline
CLASS
- endogenous catecholamine
MECHANISM OF ACTION
- direct alpha and beta adrenergic receptor agonist (vasopressor and weak inotropes)
- alpha > beta
- alpha effects:
— increased SVR -> increased afterload; increased DBP and coronary perfusion pressure
— increased venoconstriction -> increased venous return -> increased preload - beta effects:
— inotropy and chronotropy
PHARMACEUTICS
- clear, colorless solution, 2mg/mL, norepinephrine bitartrate
DOSE
- 0.1 to 1 mcg/kg/min IV via central line
INDICATIONS
- hypotension refractory to fluid resuscitation (primarily distributive shock such as septic shock, neurogenic shock, post-bypass vasoplegia and drug-induced)
ADVERSE EFFECTS
- hypertension
- reflex bradycardia
- hyperglycaemia
- increased afterload and beta effects may increased myocardial work and oxygen consumption
- peripheral ischaemia
PHARMACOKINETICS
- Absorption – IV (preferably via CVL)
- Distribution – small Vd
- Metabolism – MAO and COMT
- Elimination – short t1/2, unchanged in urine
Evidence
Cochrane Review 2011
- 23 RCT’s
- n = 3212
- 6 different vasopressors (alone or in combination with dobutamine or dopexamine)
- -> dopamine: increased risk of arrhythmias
- -> no significant evidence to say that one is better than the other
VAAST Trial 2008 NEJM
- DB MC RCT
- n = 780
- Vasopressin vs noradrenaline
- Patients on low dose Norad randomised to Vasopressin vs Norad
- -> no significant difference in mortality @ 28 days
CAT Study, 2009 Int Care Med
- Australasian MC DB RCT
- Noradrenaline vs Adrenaline to treat hypotension (sepsis or cardiogenic failure)
- n = 208
- -> no significant difference in mortality, LOS, ventilation, shock duration
- -> adrenaline – transient lactic acidosis, hyperglycaemia, tachycardia
Annane et al, 2007 Lancet
- MC RCT
- n = 330
- noradrenaline vs adrenaline in Septic Shock
- -> no significant difference: mortality, BP, time to haemodynamic stability, duration of vasopressor therapy, time to organ dysfunction resolution, adverse effects
- -> criticisms = underpowered, methodology suboptimal, strict inclusion criteria
Martin et al, 2000 CCM
- effect of norepinephrine on the outcome of septic shock
- n = 97 adults septic shock
- low dose dopamine then randomized to high dose dopamine vs noradrenaline
- adrenaline added if non-responding
- -> use of noradrenaline strongly related (p<0.001) to favorable outcome considered protective, markedly decreased hospital mortality
- -> Splanchnic function not worsened by NA
References and Links
Journal articles
- Myburgh J. Norepinephrine: more of a neurohormone than a vasopressor. Crit Care. 2010;14(5):196. doi: 10.1186/cc9246. Epub 2010 Sep 20. PMC3219251.
- Myburgh JA. An appraisal of selection and use of catecholamines in septic shock – old becomes new again. Crit Care Resusc. 2006 Dec;8(4):353-60. Review. PubMed PMID: 17227275.
FOAM and web resources
- Resus.ME — Norepinephrine increases preload (2011)
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.
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