Vasopressors are used frequently by the anaesthesiologists and intensivists, both inside the operation theatres (OT) and in intensive care unit (ICU) in the management of hypotension due to various causes. Following is a review of use of different vasopressors commercially available in India.
Use of vasopressors to treat hypotension is often supportive and temporary, i.e., the underlying primary cause of hypotension should be simultaneously addressed.
Vasopressors can be grouped as
- Non catecholamine synthetic sympathomimetic agents: Ephedrine and Mephentermine
- Catecholamines: Phenylephrine, adrenaline, noradrenaline, dopamine and dobutamine.
Role of individual drugs
Ephedrine, an alkaloid, originally extracted from plant source, is a synthetic non catecholamine sympathomimetic agent, with effects on both alpha and beta receptors.
Available as 30mg/mL in 1 mL ampoule and 10 mL vials, commonly diluted with normal saline to 6mg/mL in a 5 mL syringe.
Ephedrine due to its β receptor stimulating effects, increases myocardial contractility and causes tachycardia. It also acts by releasing noradrenaline at sympathetic nerve endings.
Treatment of transient hypotension episodes
- Hypotension induced by spinal anaesthesia: ephedrine has been used in various doses and by different routes for this purpose. As a rule, hypotension is treated when the reduction of BP is more than 20% from the baseline. Dose is 6 mg incremental IV boluses. Intramuscular ephedrine has also been used, but generally not recommended because of erratic absorption and also remote risk of rebound hypertension. Ephedrine is one of the preferred vasopressors in obstetric spinal anaesthesia due to its lack of adverse effects on uterine circulation.
- Hypotension during induction with propofol, though transient, can be sometimes severe. Bolus doses of 6 mg ephedrine IV can be administered.
- Hypotension due to other causes: Ephedrine can be used for transient support of blood pressure.
For hypotension that is severe and prolonged or is due to conditions like anaphylaxis, sepsis, arrhythmias. Ephedrine is not the ideal choice. Such patients may require adrenaline, nor adrenaline and adenosine (if it is supraventricular tachycardia) by infusion as the case may be.
Phenylephrine hydrochloride is a non catecholamine synthetic sympathomimetic agent and α1 agonist.
Phenylephrine is a pure α agonist. It causes vasoconstriction without tachycardia.
- To treat transient hypotension due to causes like spinal anaesthesia, especially in obstetric anaesthetic practice.
- Hypotension due to supraventricular tachycardia
- Hypotension in patients with fixed cardiac outputs, like MS, AS, HOCM, as tachycardia is dangerous in these patients.
- Useful for minimizing right to left shunting of blood during cyanotic spells observed in children with Fallot’s tetralogy
Available as 30 mg/mL in 10 mL vial. Diluted with normal saline to 3-6 mg/mL and administered as one to two mL bolus.
This is an indirectly-acting vasopressor that acts on both the α and β receptors.
Similar to that of ephedrine except that it may not be the drug of choice in LSCS as mephentermine might cause uterine artery constriction.
Adrenaline has a wide range of applications in clinical practice and is the most important emergency drug, always kept ready for use in anaesthesia and critical care.
Naturally occurring catecholamine synthesized in adrenal medulla, by addition of a methyl group to noradrenaline.
Physiology and pharmacology
The synthesis of adrenaline is similar to that of noradrenaline (see below). Adrenaline has significant effects on all the subtypes of α (1 and 2) and β (1,2,3) receptors resulting in
- Positive inotropy and chronotropy
- Enhanced conduction of heart (β1)
- Bronchial relaxation (β2)
- Vasoconstriction, which causes increased aortic diastolic pressure leading to improved coronary perfusion. This is the most important beneficial effect of adrenaline during cardiopulmonary resuscitation (CPR).
- Increased levels of glucose, lactate and free fatty acids
Indications and doses
- Cardiac arrest (Ventricular fibrillation, pulseless ventricular tachycardia, pulseless electrical activity, asystole): 1mg IV, repeated every 3-5 min. High dose adrenaline of 0.2mg/kg has not been found to improve survival after cardiac arrest. In children, it is administered as 10µg/Kg IV bolus repeated every 3-5 minutes. High doses of 0.2mg/kg also have been successfully used.
- Anaphylactic shock: It is used in a dose of 50-100 µg bolus IV or 0.5 mg intramuscularly if IV access is not possible.
- Bone cement reactions during arthroplasty and joint replacement surgery – it is used in a dose of 25-50 µg bolus IV
- Symptomatic bradycardia not responding to atropine IV – used as an IV infusion adrenaline 2-10 µg/min
- As an additive to local anaesthetic drugs to minimize vascular absorption of the drug and to increase the duration of action of the local anaesthetic agent: Used in a concentration of 1:200,000 (5 µg/mL). Maximum dose of adrenalin are not to exceed total of 5micrograms/kg.
- In a concentration of 1:200,000 (5 µg/mL), it is also used to reduce the bleeding at the surgical site. Caution to be used when volatile anaesthetic is used for anaesthesia with the dose of adrenaline – maximum safe dose of adrenaline 3 µg/kg with halothane, 6 µg/kg with isoflurane and 10 µg/kg with sevoflurane
- To detect unintentional intravascular insertion / migration of the epidural catheter: 3 mL lignocaine 2% with 1:200,000 (5µg/mL) is injected through the epidural catheter. If the epidural catheter is in a vessel, usually it manifests with sudden increase in heart rate by >10 beats (sustained for >30 seconds) within 30 seconds of injection of the epidural test dose
- Severe intractable bronchospasm – Subcutaneous adrenaline 0.5-1 mg was used previously. Now with widespread availability of intravenous lines, 25-50 µg bolus IV can be used.
- Racemic epinephrine – This is a mixture of levo and dextro-isomers of adrenaline administered in the form of nebulisation. This causes less tachycardia and is used to treat laryngeal oedema. The dose is 0.75 mL, 0.5 mL and 0.25 mL in adults, children and infants respectively (diluted to 3-5 mL with normal saline for nebulisation).
Adrenaline that is commercially available in India is Levo adrenaline. Racemic adrenaline is available only on special order.
- Septic shock – 0.05-0.2 µg/kg/min as a vasopressor and inotrope
It is the naturally occurring catecholamine and synthesised from tyrosine as follows:
- Tyrosine is synthesised from phenylalanine
- Tyrosine is converted to DOPA (dihydroxyphenylalanine) by tyrosine hydroxylase
- Dopa is decarboxylated to dopamine by DOPA decarboxylase
- Conversion of dopamine to noradrenaline by dopamine beta hydroxylase
|Structurally, noradrenaline differs from adrenaline by a lack of methyl group.|
Clinical importance and application is due to its potent α-stimulation effects which increases systemic vascular resistance. Has a short half-life of only 2.5 min, hence usually used as infusion.
Physiological effects of noradrenaline infusion
- Dose less than 30ng/kg/min uncovers β-stimulatory effects
- Dose more than 30ng/kg/min significant α-stimulation
- Increases myocardial oxygen demand
- Reflex bradycardia may occur with increase in blood pressure following administration of noradrenaline
- Cardiac output remains unchanged
- Increases pulmonary vascular resistance, hence should be careful in patients with pulmonary hypertension
- Vasoconstriction in renal, hepatic and mesenteric vessels, leading to potential for hypoperfusion, ischaemia of liver, kidney and bowels. Hepatic hypoperfusion can affect clearance of drugs like lignocaine.
- Tissue necrosis and gangrene if extravasation occurs. Phentolamine is the drug of choice for treatment.
Clinical application and precautions
- First line drug for treatment of septic shock. Can be used in other causes of hypotension also
- Always administered as infusion
- Arterial blood pressure monitoring is mandatory
- Monitor the site of infusion for extravasations
- Noradrenaline should be carefully used in patients with IHD, PHT or other major organ dysfunction
- Low dose dopamine infusion can be combined to offset the renal effects.
Dopamine hydrochloride – a naturally occurring catecholamine that has dose dependent effects on both α and β adrenergic receptors as well as dopaminergic receptors. In addition to being a precursor of noradrenaline, dopamine itself acts to release noradrenaline, thus having both direct and indirect effects.
Half life: 1 minute, ideal for infusion
- At the lowest dose of 0.5-2mcg/kg/min dopamine has predominant dopaminergic effect (DA1 receptor) causing vasodilatation in renal and mesenteric vascular beds.
- 2-10 µg/kg/min causes α and β stimulation causing increased cardiac contractility and output. At a dose > 5µg/kg/min, it stimulates release of noradrenaline also.
- 10-20 µg/kg/min causes predominantly α-effects resulting in significant vasoconstriction and offsets the vasodilatory effects of low dose.
- Role in shock; to preserve renal function.
It is synthetic analogue of dopamine, described as inotropic vasodilator, specifically useful in presence of congestive cardiac failure. Compared to the parent compound, dopamine, dopexamine is a) 60 times more potent at β2 receptors b) one third potency at DA1 receptors and c) one seventh as potent at DA2 receptors. Also, with dopexamine, α and β1 adrenergic effect are insignificant.
β2 stimulation causes systemic vasodilatation and indirect inotropic activity (due to neuronal uptake inhibition)
Dobutamine is synthetic analogue of dopamine with predominantly β1 adrenergic effects and minimal effects on β2 and α1 receptors. It does not cause endogenous release of norepinephrine and has no action on dopaminergic receptors. It is available as 5 mL ampoule with 50 mg/mL strength. Used in dose of 2-20 µg/kg/min. Dose above 20µg/kg/min produces tachycardia.
Congestive heart failure (CHF) and myocardial infarction (MI) with low cardiac output. It doesn’t increase the size of infarct and does not cause significant arrhythmia. Also, due to lack of effects on endogenous catecholamine release, Dobutamine is effective in catecholamine depleted states. However, in chronic conditions, down regulation of β receptors reduces the effectiveness.
Continuous administration for more than 3 days produces tachyphylaxis and prolonged infusions as in case of chronic heart failure can cause down regulation of β receptors.
Pharmacological phenomenon where prolonged administration of a drug (hours to days, depending on the drug) results progressively less response. However, the toxicity potential will increase.
A potent vasopressor, available in 2 mL ampoules containing 20 IU/mL of synthetic vasopressin (arginine vasopressin). It is used for resistant septic shock where the blood pressure does not respond well to high doses of dopamine and noradrenaline. It is also useful in the management of anaphylactic shock and as an alternative to first or second dose of adrenaline during cardiopulmonary resuscitation (CPR).
2015 CPR guidelines:
It is administered in a dose of 0.01-0.04 IU/min (0.6-2.4 IU/h) for septic shock and anaphylactic shock while the dose for CPR is 40 IU as a bolus.