This topic was selected because an evidence synthesis beats a textbook on it: the trials disagree, or the guidance has moved recently.
THE EVIDENCE
What each source contributes, and how strong it is
Study design first — a cohort and a randomised trial do not carry the same weight.
Design
Year
Journal
What it found
Meta-analysis
2020
Anaesthesia
Ranked across 109 trials of spinal anaesthesia for caesarean section, metaraminol,
Randomised trial
2015
Anesthesiology
Given by infusion, norepinephrine held systolic pressure as well as phenylephrine
Meta-analysis
2020
British journal of anaesthesia
Norepinephrine, metaraminol
Randomised trial
2019
Anesthesia and analgesia
Using equipotent boluses, bradycardia occurred in 11% with norepinephrine 6
Meta-analysis
2024
Anaesthesia
Phenylephrine raises blood pressure while lowering cardiac output
Randomised trial
2017
Anesthesiology
Norepinephrine 8 micrograms is about equivalent to phenylephrine 100 micrograms, a
6 resolved citations behind this deck; every point above traces to one of them.
WHERE THE GUIDANCE SITS
What the guidelines and pooled evidence say
3 findings, each on the slide that follows.
Anaesthesia 2020
Ranked across 109 trials of spinal anaesthesia for caesarean section, metaraminol,
Ranked across 109 trials of spinal anaesthesia for caesarean section, metaraminol, norepinephrine and phenylephrine were the most effective at…
British journal of anaesthesia 2020
Norepinephrine, metaraminol
Norepinephrine, metaraminol
Anaesthesia 2024
Phenylephrine raises blood pressure while lowering cardiac output
Phenylephrine raises blood pressure while lowering cardiac output
WHERE THE GUIDANCE SITS
Ranked across 109 trials of spinal anaesthesia for caesarean section, metaraminol,
Meta-analysis · Anaesthesia
Ranked across 109 trials of spinal anaesthesia for caesarean section, metaraminol, norepinephrine and phenylephrine were the most effective at preventing hypotension, while crystalloid given before induction was no better than control.
Prevention of Hypotension After Spinal Anaesthesia for Caesarean Section: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials, Anaesthesia 2020 · PMID 31531852
WHERE THE GUIDANCE SITS
Norepinephrine, metaraminol
Meta-analysis · British journal of anaesthesia
Norepinephrine, metaraminol, and mephentermine may have a lower probability of adversely affecting fetal acid-base status (umbilical arterial base excess) compared to phenylephrine during Caesarean delivery under neuraxial anesthesia.
Vasopressor Drugs for the Prevention and Treatment of Hypotension During Neuraxial Anaesthesia for Caesarean Delivery: A Bayesian Network Meta-Analysis of Fetal and Maternal Outcomes, British journal of anaesthesia 2020 · PMID 31810562
WHERE THE GUIDANCE SITS
Phenylephrine raises blood pressure while lowering cardiac output
Meta-analysis · Anaesthesia
Phenylephrine raises blood pressure while lowering cardiac output, and although it increases cerebral blood flow it decreases cerebral tissue oxygen saturation.
Effects of Phenylephrine on Systemic and Cerebral Circulations in Humans: A Systematic Review With Mechanistic Explanations, Anaesthesia 2024 · PMID 37948131
WHAT THE TRIALS FOUND
Where randomised evidence moved the question
3 findings, each on the slide that follows.
Anesthesiology 2015
Given by infusion, norepinephrine held systolic pressure as well as phenylephrine
Given by infusion, norepinephrine held systolic pressure as well as phenylephrine but with a higher heart rate and cardiac output, lower systemic…
Anesthesia and analgesia 2019
Using equipotent boluses, bradycardia occurred in 11% with norepinephrine 6
Using equipotent boluses, bradycardia occurred in 11% with norepinephrine 6 micrograms versus 38% with phenylephrine 100 micrograms
Anesthesiology 2017
Norepinephrine 8 micrograms is about equivalent to phenylephrine 100 micrograms, a
Norepinephrine 8 micrograms is about equivalent to phenylephrine 100 micrograms, a potency ratio near 13 to 1, so the two cannot be swapped at the…
WHAT THE TRIALS FOUND
Given by infusion, norepinephrine held systolic pressure as well as phenylephrine
Randomised trial · Anesthesiology
Given by infusion, norepinephrine held systolic pressure as well as phenylephrine but with a higher heart rate and cardiac output, lower systemic vascular resistance and less bradycardia.
Randomized Double-Blinded Comparison of Norepinephrine and Phenylephrine for Maintenance of Blood Pressure During Spinal Anesthesia for Cesarean Delivery, Anesthesiology 2015 · PMID 25635593
WHAT THE TRIALS FOUND
Using equipotent boluses, bradycardia occurred in 11% with norepinephrine 6
Randomised trial · Anesthesia and analgesia
Using equipotent boluses, bradycardia occurred in 11% with norepinephrine 6 micrograms versus 38% with phenylephrine 100 micrograms, and fewer patients needed rescue ephedrine.
Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent and Treat Spinal-Induced Hypotension in Cesarean Deliveries: Randomized Controlled Trial, Anesthesia and analgesia 2019 · PMID 30113395
THE NUMBERS
Norepinephrine boluses cause far less bradycardia
Equipotent boluses: norepinephrine 6 µg vs phenylephrine 100 µg.
At equipotent doses the bradycardia burden is roughly a quarter that of phenylephrine.
Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent and Treat Spinal-Induced Hypotension in Cesarean Deliveries: Randomized Controlled Trial, Anesthesia and analgesia 2019 · PMID 30113395
WHAT THE TRIALS FOUND
Norepinephrine 8 micrograms is about equivalent to phenylephrine 100 micrograms, a
Randomised trial · Anesthesiology
Norepinephrine 8 micrograms is about equivalent to phenylephrine 100 micrograms, a potency ratio near 13 to 1, so the two cannot be swapped at the same numerical dose.
A Random-Allocation Graded Dose-Response Study of Norepinephrine and Phenylephrine for Treating Hypotension During Spinal Anesthesia for Cesarean Delivery, Anesthesiology 2017 · PMID 28872480
THE NUMBERS
The two drugs are not interchangeable by number
Dose giving a 50% response, from a graded dose-response study.
Norepinephrine 8 µg ≈ phenylephrine 100 µg — a potency ratio near 13 to 1.
A Random-Allocation Graded Dose-Response Study of Norepinephrine and Phenylephrine for Treating Hypotension During Spinal Anesthesia for Cesarean Delivery, Anesthesiology 2017 · PMID 28872480
IN THE ROOM
What this changes about the next case
Colour is the strength of the evidence behind each step, not the urgency.
1
1
Ranked across 109 trials of spinal anaesthesia for caesarean section, metaraminol, norepinephrine and phenylephrine were the most effective at preventing hypotension, while crystalloid given before induction was no better than control.
2
2
Norepinephrine, metaraminol, and mephentermine may have a lower probability of adversely affecting fetal acid-base status (umbilical arterial base excess) compared to phenylephrine during Caesarean delivery under neuraxial anesthesia.
3
3
Phenylephrine raises blood pressure while lowering cardiac output, and although it increases cerebral blood flow it decreases cerebral tissue oxygen saturation.
4
4
Given by infusion, norepinephrine held systolic pressure as well as phenylephrine but with a higher heart rate and cardiac output, lower systemic vascular resistance and less bradycardia.
5
5
Using equipotent boluses, bradycardia occurred in 11% with norepinephrine 6 micrograms versus 38% with phenylephrine 100 micrograms, and fewer patients needed rescue ephedrine.
The oral-boards stem on the next slide puts these into one scenario.
KEY TAKEAWAYS
What to carry into the next case
Ranked across 109 trials of spinal anaesthesia for caesarean section, metaraminol,
Anaesthesia 2020
Given by infusion, norepinephrine held systolic pressure as well as phenylephrine
Anesthesiology 2015
Norepinephrine, metaraminol
British journal of anaesthesia 2020
Using equipotent boluses, bradycardia occurred in 11% with norepinephrine 6
Anesthesia and analgesia 2019
Ranked across 109 trials of spinal anaesthesia for caesarean section, metaraminol,
Questions I'll ask you in the room
How does your plan change if the patient is not optimised?
What is the physiology behind what we just did?
Talk me through the trade-off you made there.
What would make you abandon this plan and do something else?
Oral boards stem
Ten minutes after a spinal for a total knee replacement, the blood pressure falls from 148/82 to 84/44 with a heart rate of 52. You reach for a vasopressor and the resident asks which one and why.
Board questions
1. State the approximate equipotent dose relationship between norepinephrine and phenylephrine for treating spinal hypotension, and the practical consequence for dosing.
Show answer
Norepinephrine 8 micrograms is about equivalent to phenylephrine 100 micrograms, a potency ratio near 13 to 1, so the two drugs cannot be swapped at the same numerical dose.
Roughly 13 to 1 — if you carry a phenylephrine microgram number over to norepinephrine, you are an order of magnitude off.
A Random-Allocation Graded Dose-Response Study of Norepinephrine and Phenylephrine for Treating Hypotension During Spinal Anesthesia for Cesarean Delivery, Anesthesiology 2017 · PMID 28872480
2. Comparing norepinephrine and phenylephrine given by infusion during spinal anaesthesia, describe how they compare for systolic pressure control and for heart rate, cardiac output, systemic vascular resistance and bradycardia.
Show answer
Given by infusion, norepinephrine held systolic pressure as well as phenylephrine, but with a higher heart rate and cardiac output, a lower systemic vascular resistance, and less bradycardia.
Both agents defend the systolic pressure — the difference is what sits behind it, with norepinephrine preserving more heart rate and cardiac output and less bradycardia.
Randomized Double-Blinded Comparison of Norepinephrine and Phenylephrine for Maintenance of Blood Pressure During Spinal Anesthesia for Cesarean Delivery, Anesthesiology 2015 · PMID 25635593
3. You give phenylephrine for hypotension. Describe its effect on blood pressure and cardiac output, and what happens to cerebral blood flow and to cerebral tissue oxygen saturation.
Show answer
Phenylephrine raises blood pressure while lowering cardiac output, and although it increases cerebral blood flow it decreases cerebral tissue oxygen saturation.
A better cuff number and even a higher cerebral blood flow can still come with a fall in cerebral tissue oxygen saturation — the pressure is not the tissue.
Effects of Phenylephrine on Systemic and Cerebral Circulations in Humans: A Systematic Review With Mechanistic Explanations, Anaesthesia 2024 · PMID 37948131
4. A network meta-analysis of 109 trials ranked strategies for preventing post-spinal hypotension. Which agents ranked most effective, what did it find about crystalloid given before induction, and what feature of the included trials limits how directly you can apply the ranking to a patient having a knee replacement?
Show answer
Metaraminol, norepinephrine and phenylephrine were the most effective at preventing hypotension, and crystalloid given before induction was no better than control. All 109 trials were of spinal anaesthesia for caesarean section, so the ranking comes from an obstetric population rather than from non-obstetric surgical patients.
The vasopressor ranking is strong, but it is obstetric data — and note that in it, crystalloid before induction did not beat control.
Prevention of Hypotension After Spinal Anaesthesia for Caesarean Section: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials, Anaesthesia 2020 · PMID 31531852
The bottom lineRanked across 109 trials of spinal anaesthesia for caesarean section, metaraminol,
Sources
[1] Prevention of Hypotension After Spinal Anaesthesia for Caesarean Section: A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials, Anaesthesia 2020 · PMID 31531852 open
[2] Randomized Double-Blinded Comparison of Norepinephrine and Phenylephrine for Maintenance of Blood Pressure During Spinal Anesthesia for Cesarean Delivery, Anesthesiology 2015 · PMID 25635593 open
[3] Vasopressor Drugs for the Prevention and Treatment of Hypotension During Neuraxial Anaesthesia for Caesarean Delivery: A Bayesian Network Meta-Analysis of Fetal and Maternal Outcomes, British journal of anaesthesia 2020 · PMID 31810562 open
[4] Comparison of Intermittent Intravenous Boluses of Phenylephrine and Norepinephrine to Prevent and Treat Spinal-Induced Hypotension in Cesarean Deliveries: Randomized Controlled Trial, Anesthesia and analgesia 2019 · PMID 30113395 open
[5] Effects of Phenylephrine on Systemic and Cerebral Circulations in Humans: A Systematic Review With Mechanistic Explanations, Anaesthesia 2024 · PMID 37948131 open
[6] A Random-Allocation Graded Dose-Response Study of Norepinephrine and Phenylephrine for Treating Hypotension During Spinal Anesthesia for Cesarean Delivery, Anesthesiology 2017 · PMID 28872480 open