Rational Vasopressor Selection
Allison Janda, MD
Assistant Professor, Department of Anesthesiology
University of Michigan
Rational? Vasopressor Selection
Allison Janda, MD
Assistant Professor, Department of Anesthesiology
University of Michigan
Disclosures
I have financial relationship(s) with:
Grant / Research:
PCORI – Co-investigator, “Trajectories of Recovery after Intravenous Propofol vs. Inhaled
Volatile Anesthesia (THRIVE)” PI: Kheterpal/Avidan
Grant / Research (current):
NIH R01 – Co-investigator, 1R01LM01389401 “A scalable service to improve health care
quality through precision audit and feedback” PI: Landis-Lewis
NIH R01 - Co-investigator, 1R01DK13322601 “Cardiac sURgery anesthesia Best
practices to reduce Acute Kidney Injury (CURB-AKI) PI: Mathis/Singh
Grant / Research:
NIH T32 Research Fellowship Grant – 5T32GM103730-07 (past)
Grant / Research:
Becton Dickinson and Company (past)
DEPARTMENT OF ANESTHESIOLOGY
Learning Objectives
DEPARTMENT OF ANESTHESIOLOGY
● Recall vasopressor pharmacology and physiology
● Critically evaluate the literature surrounding vasopressor selection
● Apply the evidence supporting use of various vasopressors to daily clinical
practice
DEPARTMENT OF ANESTHESIOLOGY
● Phenylephrine
● Ephedrine
● Vasopressin
● Dilute norepinephrine
● Concentrated norepinephrine
● Epinephrine
● Dopamine
● Angiotensin II
Vasopressors
• End-organ dysfunction is a major issue for surgical patients significantly
impacting quality of life, recovery after surgery, and cost of care
1-8
DEPARTMENT OF ANESTHESIOLOGY
• Improved outcomes while maintaining intraoperative blood pressures
1-7
• Vasopressor therapies, specifically the choice between phenylephrine and
norepinephrine, are debated
9-13
Background
DEPARTMENT OF ANESTHESIOLOGY
Hypotension & Postoperative Outcomes
1-7
Vasopressors
DEPARTMENT OF ANESTHESIOLOGY
● Phenylephrine
● Ephedrine
● Vasopressin
● Dilute norepinephrine
● Concentrated norepinephrine
● Epinephrine
● Dopamine
● Angiotensin II
DEPARTMENT OF ANESTHESIOLOGY
● What patient or surgical factors contribute to your choice of vasopressor?
● What vasopressor options are available at each of your operative sites?
● Are there challenges to obtaining or using various options?
● Do we even know what the “best” option is?
● Which options are safe via peripheral IVs?
Rational Selection? Or Selection by Default?
Vasopressors
DEPARTMENT OF ANESTHESIOLOGY
14
Khanna A, English SW, Wang XS, et al. Angiotensin II for the Treatment of Vasodilatory Shock. The New England journal of medicine. 2017;377(5):419-430
DEPARTMENT OF ANESTHESIOLOGY
Dose Equivalency
Dose Equivalency
Infographic created by Jonathan P.
Wanderer, Vanderbilt University Medical
Center, Anesthesiology, 2017
15
DEPARTMENT OF ANESTHESIOLOGY
DEPARTMENT OF ANESTHESIOLOGY
● Studies show norepinephrine is potentially superior to phenylephrine for
some patient populations, given improved cardiac output
8-12
Literature - Phenylephrine and Norepinephrine
DEPARTMENT OF ANESTHESIOLOGY
● ICU patients: phenylephrine was associated with increased
mortality during a norepinephrine drug shortage
10
Literature - Phenylephrine and Norepinephrine
DEPARTMENT OF ANESTHESIOLOGY
● OB patients: improved cardiac indices were found with
norepinephrine compared to phenylephrine when used during
cesarean section
12, 13
Literature - Phenylephrine and Norepinephrine
DEPARTMENT OF ANESTHESIOLOGY
● No association between dilute peripheral norepinephrine infusions and
complications due to peripheral IV extravasation or adverse events in
>14,000 patients
16
● Other studies also showed no increase in complications of IV extravasation
with dilute peripheral norepinephrine
12, 13, 16-18
New Safety Data - Dilute Norepinephrine
DEPARTMENT OF ANESTHESIOLOGY
Pancaro et al, Anesthesia and Analgesia, 2019
16
New Safety Data - Dilute Norepinephrine
DEPARTMENT OF ANESTHESIOLOGY
Pancaro et al, Anesthesia and Analgesia, 2019
16
New Safety Data - Dilute Norepinephrine
DEPARTMENT OF ANESTHESIOLOGY
Estimated risk of 0–2 adverse events per 10,000 patients
(95% CI of 0%–0.021%)
Zero Complications
Pancaro et al, Anesthesia and Analgesia, 2019
16
New Safety Data - Dilute Norepinephrine
DEPARTMENT OF ANESTHESIOLOGY
● A reduced the risk of postoperative organ dysfunction was found with
norepinephrine compared to ephedrine, but this study is confounded by
different blood pressure thresholds in each protocol
5
● Ephedrine has been associated with worsened fetal acidosis compared to
phenylephrine and norepinephrine
19,20
Literature - Ephedrine
DEPARTMENT OF ANESTHESIOLOGY
● Vasopressin can be used as an adjunct to norepinephrine for septic shock
but does not improved mortality
21
● In the VANISH trial, early use of vasopressin compared with norepinephrine
did not improve the number of kidney failure–free days
22
● Preferential vasoconstriction of the systemic circulation, sparing the
pulmonary circulation, great choice for pulmonary hypertension
23
Literature - Vasopressin
DEPARTMENT OF ANESTHESIOLOGY
● For septic shock, dopamine is associated with greater mortality and a higher
incidence of arrhythmic events compared to norepinephrine administration
24
● Dopamine is able to be administered through a peripheral IV
25
● Epinephrine for refractory hypotension or cardiac arrest
Literature - Dopamine and Epinephrine
DEPARTMENT OF ANESTHESIOLOGY
17 YEARS…
Avoiding the 17-year lag
26
…
DEPARTMENT OF ANESTHESIOLOGY
● What patient or surgical factors contribute to your choice of vasopressor?
● What vasopressor options are available at each of your operative sites?
● Are there challenges to obtaining or using various options?
● Do we even know what the “best” option is?
● Which options are safe via peripheral IVs?
Rational Selection? Or Selection by Default?
DEPARTMENT OF ANESTHESIOLOGY
*Unpublished, unadjusted data
from MPOG DataDirect
DEPARTMENT OF ANESTHESIOLOGY
● For non-cardiac cases without a central line, dilute norepinephrine use has
increased over time:
Changes in Patterns of Use at Michigan Medicine
Year Dilute norepinephrine used in any case (%) Dilute norepinephrine used in cases receiving
any vasopressor (%)
2019 2.1% 3.8%
2020 9.8% 17.3%
2021 12.3% 21.4%
DEPARTMENT OF ANESTHESIOLOGY
*Unpublished, unadjusted data
from MPOG DataDirect
DEPARTMENT OF ANESTHESIOLOGY
*Unpublished, unadjusted data
from MPOG DataDirect
DEPARTMENT OF ANESTHESIOLOGY
Road to Change
DEPARTMENT OF ANESTHESIOLOGY
Approved Vasopressors at Michigan Medicine
● Phenylephrine (peripheral or central)
● Ephedrine (peripheral or central)
● Vasopressin (ideally central)
● Concentrated norepinephrine (central only)
● Dilute norepinephrine (peripheral or central)
● Epinephrine (ideally central)
● Angiotensin II (central only)
DEPARTMENT OF ANESTHESIOLOGY
● Phenylephrine (peripheral or central)
● Ephedrine (peripheral or central)
● Vasopressin (ideally central)
● Concentrated norepinephrine (central only)
● Dilute norepinephrine (peripheral or central)
● Epinephrine (ideally central)
● Angiotensin II (central only)
Approved Vasopressors at Michigan Medicine
DEPARTMENT OF ANESTHESIOLOGY
● Peripheral administration of dilute (4 mcg/ml) norepinephrine for bolus
and/or infusion up to 0.08 mcg/kg/min, for use in adult patients in operating
rooms and procedural rooms only and access limited to anesthesia
providers
● 18g PIV or larger and adequate access to the PIV to assess site
Case example: Dilute Norepinephrine at Michigan Medicine
DEPARTMENT OF ANESTHESIOLOGY
● M&M Conference presentation
● CRNA staff meeting presentation
● Resident lecture presentations
for each class
● Multiple small-group
presentations for all PACU areas
● Emails and quality & safety
announcements
Measures for Implementation
Concentrated for Central Access:
• 64mcg/mL
• Only formulation is the infusion
bag via central line
DEPARTMENT OF ANESTHESIOLOGY
Dilute for Peripheral Access:
• 4mcg/mL
• May be used as a bolus or as
an infusion using syringe pump
Central Concentrated vs. Dilute Peripheral Dose
Concentrated for Central Access:
• 64mcg/mL
• Bag Alaris Pump Library
DEPARTMENT OF ANESTHESIOLOGY
Dilute for Peripheral Access:
• 4mcg/mL
• Syringe Alaris Pump Library
Alaris Pump Changes for Infusions
DEPARTMENT OF ANESTHESIOLOGY
*Unpublished, unadjusted data
from MPOG DataDirect
DEPARTMENT OF ANESTHESIOLOGY
Future Studies and Directions
DEPARTMENT OF ANESTHESIOLOGY
1. Monk T et al, Association between Intraoperative Hypotension and Hypertension and 30-day Postoperative Mortality in Noncardiac Surgery. Anesth 2016 Mar;124(3):741-2
2.Salmasi V, et al. Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A
Retrospective Cohort Analysis. Anesth 2017; 126:47–65
3. Walsh M, et al. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesth 2013; 119:507–15
4. Sun LY, et al. Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery. Anesth 2015; 123:515–23
5. Futier E, et al. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical
Trial. JAMA 2017; 318:1346–57
6. Wu X, et al. Optimal blood pressure decreases acute kidney injury after gastrointestinal surgery in elderly hypertensive patients: A randomized study. J Clin Anesth 2017; 43:77–83
7. Mathis MR, et al. Influence of preoperative risk on the association between hypotension and postoperative acute kidney injury: a report from the Multicenter Perioperative Outcomes Group. Anesth 2019 Nov
26.
8. Dimick JB, Chen SL, Taheri PA, Henderson WG, Khuri SF, Campbell DA Jr: Hospital costs associated with surgical complications: a report from the private-sector National Surgical Quality Improvement
Program. J Am Coll Surg 2004; 199:531–7
9. Mets B. Should norepinephrine, rather than phenylephrine, be considered the primary vasopressor in anesthetic practice? Anesth Analg 2016; 122:1707–14
10. Vail E, et al. Association Between US Norepinephrine Shortage and Mortality Among Patients with Septic Shock. JAMA 2017; 317:1433–42
11. Ducrocq N, et al. Comparison of equipressor doses of norepinephrine, epinephrine, and phenylephrine on septic myocardial dysfunction. Anesth 2012; 116:1083–91
12. Ngan Kee WD, et al. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesth 2015; 122:736–
45
13. Ngan Kee WD. A Random-allocation Graded Dose-Response Study of Norepinephrine and Phenylephrine for Treating Hypotension during Spinal Anesthesia for Cesarean Delivery. Anesthesiology.
2017127: 934-41.
14. Khanna A, English SW, Wang XS, et al. Angiotensin II for the Treatment of Vasodilatory Shock. The New England journal of medicine. 2017;377(5):419-430
15. Infographic created by Jonathan P. Wanderer, Vanderbilt University Medical Center, Anesthesiology, 2017. 126:6
16, Pancaro C, Shah N, Pasma W, Saager L, Cassidy R, Klei W van, Kooij F, Vittali D, Hollmann MW, Kheterpal S, Lirk P: Risk of Major Complications After Perioperative Norepinephrine Infusion Through
Peripheral Intravenous Lines in a Multicenter Study. Anesth Analg 2019 doi:10.1213/ANE.0000000000004445
17. Medlej K, Kazzi AA, El Hajj Chehade A, Saad Eldine M, Chami A, Bachir R, Zebian D, Abou Dagher G: Complications from Administration of Vasopressors Through Peripheral Venous Catheters: An
Observational Study. J Emerg Med 2018; 54:47–53
18. Ekeløf SA, Ekeløf S, Bech JN, Ekeløf P. Administration of norepinephrine in peripheral venous catheter on surgical patients. Ugeskr Laeger [Weekly Journal for Physicians]. 2017; 179
19. Cooper et al, Fetal and Maternal Effects of Phenylephrine and Ephedrine during Spinal Anesthesia for Cesarean Delivery. Anesth 2002; Dec;97(6):1582-90.
20. Ngan Kee and Shah. Vasopressors in obstetrics: what should we be using? Curr Opin Anaesthesiol. 2006 Jun;19(3):238-43.
21. Russell et al. Vasopressin versus Norepinephrine Infusion in Patients with Septic Shock. N Engl J Med 2008; 358:877-887.
22. Gordon et al. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016;316(5):509-518.
23. Currigan et al. Vasoconstrictor responses to vasopressor agents in human pulmonary and radial arteries: an in vitro study. Anesth; 2014 Nov;121(5):930-6.
24. Backer et al. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med. 2012 Mar;40(3):725-30.
25. Cardenas-Garcia et al. Safety of peripheral intravenous administration of vasoactive medication. J Hosp Med 2015 Sep;10(9):581-5.
26. Morris ZS, Wooding S, Grant J. The answer is 17 years, what is the question: understanding time lags in translational research. J R Soc Med. 2011;104:510–20.
References
