Phenylephrine

How to use it in theatre/ICU (practical)

Indications: treatment of hypotension due to reduced SVR (e.g. spinal/epidural sympathectomy, anaesthetic-induced vasodilation, vasoplegia), to increase MAP and coronary perfusion pressure when cardiac output is adequate.
- Often preferred when tachycardia is undesirable (e.g. fast AF, ischaemic heart disease) because it commonly causes reflex bradycardia.
Bolus dosing (adult): 50–100 micrograms IV (range 25–200 micrograms) titrated to effect; allow 1–2 minutes to assess peak effect.
- Smaller boluses (e.g. 25–50 micrograms) in elderly, hypovolaemia, severe aortic stenosis, or when hypertension is risky.
Infusion dosing (adult): commonly 0.25–1 microgram/kg/min (or 10–100 micrograms/min) titrated to target MAP; use a dedicated line where possible.
- If escalating requirements, reassess: volume status, anaesthetic depth, bleeding, sepsis/vasoplegia, myocardial function.
Preparation (common UK): 10 mg in 10 mL (1 mg/mL) ampoule; typical dilution for bolus: 1 mg in 100 mL = 10 micrograms/mL, or 1 mg in 10 mL = 100 micrograms/mL (label clearly).
- Avoid inadvertent IV administration of concentrated solution; standardise local concentrations to reduce error.
Monitoring: continuous ECG and NIBP/arterial line; watch for reflex bradycardia, hypertension, reduced stroke volume, and signs of low cardiac output.
- In patients with poor LV function, rising MAP with falling cardiac output may worsen tissue perfusion despite “good numbers”.

Choosing phenylephrine vs alternatives (quick decision)

If hypotension + tachycardia: phenylephrine may be useful (raises SVR, may slow HR).
If hypotension + bradycardia/low output: consider ephedrine, metaraminol, adrenaline/noradrenaline depending on context; phenylephrine can worsen bradycardia and reduce CO.
If septic shock/vasoplegia: noradrenaline is first-line; phenylephrine may be considered when tachyarrhythmias limit noradrenaline or as an adjunct, but can reduce splanchnic/renal perfusion if CO falls.

Class and mechanism

Synthetic sympathomimetic; predominantly selective α1-adrenoceptor agonist (minimal β activity at clinical doses).
α1 activation (Gq): ↑ IP3/DAG → ↑ intracellular Ca2+ in vascular smooth muscle → vasoconstriction (arteriolar and venous).
Physiological consequence: ↑ SVR and ↑ MAP; venoconstriction may ↑ venous return, but net CO often unchanged or reduced due to ↑ afterload and reflex bradycardia.

Cardiovascular effects (exam-friendly)

Blood pressure: ↑ systolic and diastolic; MAP rises reliably.
Heart rate: commonly ↓ via baroreceptor-mediated vagal reflex; can precipitate significant bradycardia/asystole in susceptible patients (high vagal tone, neuraxial block, opioids).
Cardiac output: may ↓ (↑ afterload + ↓ HR); particularly in hypovolaemia, RV failure, severe LV dysfunction.
Coronary perfusion: ↑ diastolic pressure may improve coronary perfusion pressure, but increased afterload can increase myocardial oxygen demand; overall balance depends on LV function and HR response.

Other organ effects

Uteroplacental blood flow: may reduce due to vasoconstriction; however, in obstetric spinal hypotension, maintaining maternal BP improves uteroplacental perfusion overall. Commonly used as infusion/bolus with careful titration.
Cerebral circulation: raises CPP by increasing MAP; excessive hypertension may be harmful (intracranial haemorrhage risk in vulnerable patients).
Renal/splanchnic: vasoconstriction may reduce regional blood flow if CO falls; interpret urine output in context of perfusion and CO.
Eye/ENT: topical use causes mucosal vasoconstriction and mydriasis (α1).

Pharmacokinetics

Route: IV bolus/infusion most common in anaesthesia; can be IM/SC/topical; oral bioavailability poor due to extensive first-pass metabolism.
Onset: rapid (within ~1 minute IV).
Duration: short after bolus (~5–20 minutes) depending on dose and patient physiology.
Metabolism: primarily by monoamine oxidase (MAO) in liver and gut; not a catechol (so not COMT substrate).
Elimination: metabolites excreted in urine.

Adverse effects

Excessive hypertension; reflex bradycardia; reduced cardiac output; myocardial ischaemia in susceptible patients.
Arrhythmias: less tachyarrhythmogenic than β-agonists; bradyarrhythmias can occur.
Peripheral and visceral ischaemia with high doses/prolonged infusions (especially if CO low).
Extravasation: local intense vasoconstriction → tissue ischaemia/necrosis.
- Management: stop infusion, aspirate via cannula if possible, elevate limb, consider local infiltration with phentolamine (α-antagonist) per local policy; surgical/plastics review if severe.

Contraindications / cautions (contextual)

Severe hypertension; severe peripheral vascular disease; caution in ischaemic heart disease, severe LV dysfunction, pulmonary hypertension/RV failure (afterload effects).
Hypovolaemia: may worsen tissue perfusion if used without volume resuscitation (treat cause).
Drug interactions: MAO inhibitors and tricyclic antidepressants can potentiate pressor response; caution with other sympathomimetics.

Comparators (frequent FRCA discussion points)

Phenylephrine vs ephedrine: phenylephrine is direct α1 agonist (↑ SVR, reflex ↓ HR); ephedrine is mixed/direct+indirect (↑ HR, ↑ contractility, ↑ CO) and relies on noradrenaline stores (tachyphylaxis).
Phenylephrine vs metaraminol: both predominantly α agonists; metaraminol has some indirect action and may increase venous return/CO more; both can cause reflex bradycardia.
Phenylephrine vs noradrenaline: noradrenaline is α1 with some β1 (supports SVR and CO); phenylephrine is purer α1 and more likely to reduce CO.

Describe the mechanism of action of phenylephrine and the intracellular signalling pathway.

Aim: receptor selectivity + second messenger + physiological effect.

Predominantly α1-adrenoceptor agonist on vascular smooth muscle.
α1 is Gq-coupled → activates phospholipase C → IP3/DAG → ↑ intracellular Ca2+ → smooth muscle contraction.
Net effect: arteriolar and venous vasoconstriction → ↑ SVR and ↑ MAP; baroreflex often causes reflex bradycardia.

What are the haemodynamic effects of phenylephrine on HR, SVR, CO and coronary perfusion?

Examiners want direction of change and the mechanism (baroreflex/afterload).

SVR increases (primary effect) → MAP increases.
HR decreases commonly due to baroreceptor-mediated vagal reflex.
CO often decreases (↑ afterload + ↓ HR), especially if hypovolaemic or poor LV function; may be unchanged in some patients if venoconstriction improves preload.
Coronary perfusion pressure may increase via higher diastolic pressure, but increased afterload can increase myocardial oxygen demand; clinical effect depends on LV function and HR.

A patient becomes hypotensive after spinal anaesthesia for Caesarean section. Why might you choose phenylephrine, and what are the downsides?

Key points: spinal sympathectomy, maternal BP, fetal effects, HR/CO trade-off.

Spinal causes sympathetic blockade → vasodilation and reduced venous return; phenylephrine restores SVR/MAP quickly.
Maintaining maternal BP supports uteroplacental perfusion; phenylephrine is widely used as bolus/infusion titrated to BP.
Downsides: reflex bradycardia and potential reduction in maternal CO, which may matter if already low (high block, hypovolaemia).
Practical: treat contributing factors (left uterine displacement, fluids as appropriate, reduce anaesthetic depth) and titrate vasopressor to target BP.

Give typical adult dosing regimens for phenylephrine (bolus and infusion) and how you would prepare it safely.

They want safe ranges, dilution, and avoidance of concentration errors.

Bolus: 50–100 micrograms IV (range 25–200 micrograms) titrated to effect.
Infusion: 0.25–1 microgram/kg/min (or ~10–100 micrograms/min) titrated to target MAP.
Preparation: be aware common stock is 10 mg/10 mL (1 mg/mL); dilute to a standard working concentration (e.g. 100 micrograms/mL for syringe boluses or 10 micrograms/mL for fine titration) and label clearly.
Safety: use standard concentrations, double-check calculations, and avoid accidental IV administration of undiluted 1 mg/mL solution.

Compare phenylephrine with ephedrine for treating intraoperative hypotension.

Common FRCA theme: direct vs indirect, HR/CO effects, tachyphylaxis.

Phenylephrine: direct α1 agonist → ↑ SVR/MAP, often ↓ HR, may ↓ CO.
Ephedrine: mixed direct and indirect sympathomimetic (releases noradrenaline) → ↑ HR, ↑ contractility, ↑ CO; less predictable if catecholamine stores depleted; tachyphylaxis with repeated doses.
Choice: phenylephrine if tachycardic; ephedrine if bradycardic/low output (e.g. high neuraxial block with bradycardia).

Why can phenylephrine cause profound bradycardia, and how would you manage it?

Look for baroreflex explanation and immediate management steps.

Rapid rise in MAP activates carotid/aortic baroreceptors → increased vagal tone → reflex bradycardia; more marked with high neuraxial block, high vagal tone, opioids, and hypovolaemia.
Management: stop/reduce phenylephrine, assess perfusion; treat contributing causes (high block, hypovolaemia). If symptomatic: atropine (or glycopyrrolate) and consider switching to a vasopressor/inotrope that supports HR/CO (e.g. ephedrine/adrenaline depending on scenario).

Outline the pharmacokinetics of phenylephrine relevant to anaesthesia (onset, duration, metabolism).

Short-acting IV vasopressor; metabolism points are frequently examined.

IV onset: within ~1 minute; peak effect typically within a couple of minutes.
Duration after bolus: ~5–20 minutes (dose- and physiology-dependent).
Metabolism: mainly by MAO; phenylephrine is not a catechol, so not metabolised by COMT.

What drug interactions are important with phenylephrine?

Expect MAOI/TCA and potentiation of pressor response.

MAO inhibitors: reduced metabolism of sympathomimetics → exaggerated/prolonged pressor response; careful titration and monitoring.
Tricyclic antidepressants: inhibit noradrenaline reuptake and can potentiate sympathomimetic effects → increased risk of hypertension/arrhythmias.
Other sympathomimetics/vasopressors: additive effects; caution with concurrent agents and with volatile-induced myocardial depression (CO may fall).

A patient with severe aortic stenosis becomes hypotensive during induction. Would phenylephrine be appropriate?

This is a classic viva: coronary perfusion vs CO/HR considerations.

Often appropriate to treat vasodilation-related hypotension because maintaining diastolic pressure supports coronary perfusion in AS.
However, avoid overshoot hypertension and bradycardia; excessive afterload and reduced HR can reduce CO. Use small titrated boluses and correct hypovolaemia.
If hypotension is due to poor contractility rather than vasodilation, consider agents that support inotropy (e.g. noradrenaline/adrenaline depending on context).

What are the risks of giving phenylephrine through a peripheral cannula and how do you manage extravasation?

They want recognition of local ischaemia and the antidote concept.

Risk: extravasation causes intense local α1-mediated vasoconstriction → pain, pallor, blistering, tissue necrosis.
Immediate actions: stop infusion, leave cannula in place to aspirate if possible, elevate limb, mark area, seek senior help.
Consider local infiltration with phentolamine (α-antagonist) per local protocol; plastics/surgical review if significant injury.

Explain why phenylephrine may worsen tissue perfusion despite improving blood pressure.

This tests understanding of MAP vs flow and afterload/CO.

Perfusion depends on flow (cardiac output) as well as pressure; phenylephrine increases afterload and can reduce HR → reduced CO.
Regional vasoconstriction can reduce microcirculatory flow (splanchnic/skin) particularly if CO is low or dose is high.
Therefore treat the cause of hypotension (e.g. hypovolaemia, myocardial depression) and use the lowest dose that achieves an appropriate target MAP.

Classify sympathomimetic drugs and place phenylephrine within the classification. Compare it with ephedrine and noradrenaline.

A common Primary FRCA pharmacology theme: classification + receptor profiles + clinical effects.

Classification (one approach): direct-acting (receptor agonists), indirect-acting (increase endogenous NA), and mixed-acting.
- Direct: phenylephrine (α1), noradrenaline (α1>α2 with β1), adrenaline (α/β), isoprenaline (β1/β2), dobutamine (β1).
- Indirect: tyramine; mixed: ephedrine, metaraminol (partly indirect).
Phenylephrine: direct α1-selective → ↑ SVR/MAP, reflex ↓ HR; minimal β effects → less tachycardia but potential ↓ CO.
Ephedrine: mixed (direct + NA release) → ↑ HR and contractility, ↑ CO; can show tachyphylaxis and is less effective when catecholamine stores depleted (e.g. prolonged critical illness).
Noradrenaline: α1 with β1 → ↑ SVR with some inotropic support; tends to maintain CO better than phenylephrine in vasodilatory shock; still can cause reflex bradycardia but usually less CO reduction than pure α agonist.

Describe the pharmacology of phenylephrine under the headings: mechanism of action, pharmacokinetics, indications, adverse effects, and contraindications/cautions.

This is a classic ‘drug viva’ structure; aim for short, accurate headings.

Mechanism: α1 agonist (Gq → IP3/DAG → ↑ Ca2+) → vasoconstriction → ↑ SVR/MAP; reflex bradycardia.
PK: IV onset rapid (~1 min); duration 5–20 min; metabolism mainly MAO (not COMT); urinary excretion of metabolites.
Indications: hypotension from vasodilation (spinal/GA), to support MAP/CPP; sometimes when tachycardia limits other agents.
Adverse effects: hypertension, reflex bradycardia, ↓ CO, myocardial ischaemia, peripheral ischaemia; extravasation injury.
Cautions: hypovolaemia, severe LV dysfunction, severe PVD; interactions with MAOI/TCA.

A patient becomes hypotensive on induction. How would you assess the cause and rationally choose phenylephrine (or not)?

This tests clinical reasoning: treat the cause, not just the number.

Rapid assessment: check depth of anaesthesia, recent drug boluses (propofol/opioid), bleeding, anaphylaxis, arrhythmia, ventilation/PEEP effects, and volume status; look at HR trend and capnography (CO surrogate).
If pattern suggests low SVR with adequate HR/contractility (warm peripheries, tachycardia or normal HR, recent neuraxial/volatile/propofol): phenylephrine is reasonable to restore MAP while addressing cause.
If bradycardia/low output (low ETCO2, poor pulse volume, bradycardia): phenylephrine may worsen CO; consider atropine + ephedrine/adrenaline and treat underlying cause (high spinal, vagal stimulus, myocardial depression).
If anaphylaxis: adrenaline is first-line; phenylephrine is not definitive therapy.