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
CCC Pharmacology Series
Respiratory: Bosentan, Delivery of B2 Agonists in Intubated Patients, Nitric Oxide, Oxygen, Prostacyclin, Sildenafil
Cardiovascular: Adenosine, Adrenaline (Epinephrine), Amiodarone, Classification of Vasoactive drugs, Clevidipine, Digoxin, Dobutamine, Dopamine, Levosimendan, Levosimendan vs Dobutamine, Milrinone, Noradrenaline, Phenylephrine, Sodium Nitroprusside (SNiP), Sotalol, Vasopressin
Neurological: Dexmedetomidine, Ketamine, Levetiracetam, Lignocaine, Lithium, Midazolam, Physostigmine, Propofol, Sodium Valproate, Sugammadex, Thiopentone
Endocrine: Desmopressin, Glucagon Therapy, Medications and Thyroid Function
Gastrointestinal: Octreotide, Omeprazole, Ranitidine, Sucralfate, Terlipressin
Genitourinary: Furosemide, Mannitol, Spironolactone
Haematological: Activated Protein C, Alteplase, Aprotinin, Aspirin, Clopidogrel, Dipyridamole, DOACs, Factor VIIa, Heparin, LMW Heparin, Protamine, Prothrombinex, Tenecteplase, Tirofiban, Tranexamic Acid (TXA), Warfarin
Antimicrobial: Antimicrobial Dosing and Kill Characteristics, Benzylpenicillin, Ceftriaxone, Ciprofloxacin, Co-trimoxazole / Bactrim, Fluconazole, Gentamicin, Imipenem, Linezolid, Meropenem, Piperacillin-Tazobactam, Rifampicin, Vancomycin
Analgesic: Alfentanil, Celecoxib, COX II Inhibitors, Ketamine, Lignocaine, Morphine, NSAIDs, Opioids, Paracetamol (Acetaminophen), Paracetamol in Critical Illness, Tramadol
Miscellaneous: Activated Charcoal, Adverse Drug Reactions, Alkali Therapies, Drug Absorption in Critical Illness, Drug Infusion Doses, Epidural Complications, Epidural vs Opioids in Rib Fractures, Magnesium, Methylene Blue, Pharmacology and Critical Illness, PK and Obesity, PK and ECMO, Sodium Bicarbonate Use, Statins in Critical Illness, Therapeutic Drug Monitoring, Weights in Pharmacology
Toxicology: Digibind, Flumazenil, Glucagon Therapy, Intralipid, N-Acetylcysteine, Naloxone, Propofol Infusion Syndrome
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, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
| INTENSIVE | RAGE | Resuscitology | SMACC