Neil Orford Taming Sepsis Presentation Cri-iq Web site



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Noradrenaline

28/10/10


Neil Orford – Taming Sepsis Presentation – Cri-iq Web site
Class - catecholamine

Mechanism of Action – direct alpha and beta adrenergic receptor agonist (vasopressor and weak inotropes)

Pharmaceutics - clear, colourless solution, 2mg/mL, norepinephrine bitartrate

Dose - 0.1 to 1mcg/kg/min IV

Indications – refractory hypotension

Adverse Effects
- hypertension

- reflex bradycardia

- hyperglycaemia
PK
Absorption – IV (preferably via CVL)

Distribution – small Vd

Metabolism – MAO and COMT

Elimination – short t1/2, unchanged in urine



Evidence

Vasopressors for Shock
- 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
- RCT (2008) - NEJM

- N = 780

- Vasopressin vs Norad

- Patients on low dose Norad randomised to Vasopressin vs Norad

-> no significant difference in mortality @ 28 days

CAT Study Investigators
- Australasian Trial (2009) – Int Care Med

- blinded RCT looking at Noradrenaline vs Adrenaline to treat hypotension (sepsis or cvs failure)

- n = 208

-> no significant difference in mortality, LOS, ventilation, shock duration

-> adrenaline – transient lactic acidosis, hyperglycaemia, tachycardia

Annane (2007) – Lancet
- MRCT

- 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 not fantastic, strict inclusion criteria

Martin C. – CCM 2000
- 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




Jeremy Fernando (2011)


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