Franciscan Health Indianapolis

Medication Use Evaluation

Pharmacy and Therapeutics Committee

DATE PRESENTED TO P&T COMMITTEE: 10/2/2023

PRESENTED BY: Hannah Klemm, PharmD

TOPIC: Phenylephrine for Septic Shock

SAMPLE: Patients who were admitted to the ICU at Franciscan Health Indianapolis and received vasopressor support for
the management of septic shock between January 1st, 2023 through July 7th, 2023 were selected for review.

CRITERIA: Patients who were managed with phenylephrine as a first- or second-line vasopressor (in lieu of both
norepinephrine and vasopressin) were evaluated for surviving sepsis guideline-recommended vasopressor therapy,
duration of ICU stay, average heart rate and blood pressure, duration of vasopressor use, and lactate levels throughout
treatment.

REFERENCES:
1. Phenylephrine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. June 27, 2023. Accessed July 6, 2023.
http://online.lexi.com
2. He D, Hu H, Hong L, Zhang L, Lu X, Gu WJ, Lyu J, Yin H. Norepinephrine combined with phenylephrine versus
norepinephrine in patients with septic shock: a retrospective cohort study. BMC Infect Dis. 2023 Apr 7;23(1):221.
doi: 10.1186/s12879-023-08142-x.
3. Haiduc M, Radparvar S, Aitken SL, Altshuler J. Does Switching Norepinephrine to Phenylephrine in Septic Shock
Complicated by Atrial Fibrillation With Rapid Ventricular Response Improve Time to Rate Control? J Intensive
Care Med. 2021 Feb;36(2):191-196. doi: 10.1177/0885066619896292.

RATIONALE: □ high risk □ high volume □ high cost X problem prone

Phenylephrine is a pure, direct-acting alpha1-agonist FDA approved for the treatment of hypotension during shock and
during anesthesia. This alpha activity produces vasoconstriction of the systemic arterials leading to an increase in blood
pressure and is titrated to a desired mean arterial pressure (MAP). The initial dosing for a continuous infusion is 40 – 160
mcg/min. Doses up to 730 mcg/min have been studied; however, they are associated with more adverse effects, such as
reflex bradycardia and angina1.

According to the Surviving Sepsis Guidelines, norepinephrine is recommended as the first-line agent over other
vasopressors. The guidelines endorse vasopressin as a second line/adjunctive agent to norepinephrine to reduce concomitant
catecholamine requirements when titrating to restore adequate perfusion, as well as dobutamine or epinephrine in the setting of
sepsis with cardiac dysfunction. As per the other vasopressors, vasopressin and epinephrine are strongly recommended for
use in septic shock as an add on therapy to norepinephrine to reach an adequate MAP. Currently, phenylephrine is not
recommended for use by the guidelines. A study published in 2023 by He et al analyzed 1,747 patients with septic shock
to compare mortality and hospital length of stay in those managed with norepinephrine vs both norepinephrine and
phenylephrine. The results showed a statically significant decrease in ICU length of stay in patients managed with
norepinephrine (p<0.001) as well as similar length of hospital stay and duration of mechanical ventilation. The study
concluded that the combination of norepinephrine plus phenylephrine was inferior to norepinephrine by itself2.
Additionally, a retrospective study by Haiduc et al evaluated patients who developed atrial fibrillation with rapid ventricular
rate while receiving norepinephrine monotherapy and were then subsequently switched to phenylephrine. The primary
endpoint included attainment of rate control and secondary endpoint focused on mortality and length of ICU stay. The
results supported that the use of phenylephrine may have a potential benefit over norepinephrine in achieving rate control
in patients with atrial fibrillation with rapid ventricular rate (unadjusted hazard ratio; p < 0.01), however there was no
difference in mortality or ICU length of stay between the two groups was reported.3 With the variable data on the use of
phenylephrine in septic shock, it is important to consider individual patients and their risks versus benefits to determine if
this therapy is appropriate.

This document is protected by the HCQIA 1986, 42 U.S.C. Sec. – 1102, et seq., and by Indiana Peer Review Act, Indiana Code Sec. 34-4-12.6-1, et
seq. All privileges or the immunities of these statutes are claimed.
FINDINGS:
• A total of seventy-six patients who received phenylephrine during their ICU admission were reviewed.
• The average length of ICU stay for patients receiving phenylephrine was 9.7 days.
• Those who had a past medical history of pulmonary hypertension had an extended length of stay (11.5 days)
compared to those who did not have a history of pulmonary hypertension (9.7 days).
• Out of the seventy-six patients reviewed, 56 (74%) were not treated with Surviving sepsis guideline
recommendations prior to their initiation of phenylephrine.
• Thirty percent of patients did not have appropriate lactate levels redrawn at either the six- or twelve-hour mark.
Patient Baseline Comorbidities (No. %)
Atrial Fibrillation 37 (48.7%)
Heart Failure with Reduced Ejection Fraction (EF < 40%) 23 (30.3%)
Pulmonary Hypertension 17 (22.4%)
Mechanical Ventilation 30 (39.5%)

Patient Prior to PE 3 Hours after PE

Characteristics
Average MAP 71 mmHg 71 mmHg
Average Heart Rate 114 bpm 110 bpm

Patient Average lactate Average lactate 6 Average lactate

Characteristics prior to PE hours post PE 12 hours post PE
Lactate 3.8 mmol/L 5.6 mmol/L 5.4 mmol/L

CONCLUSIONS:
• 74% of patients who received phenylephrine did not receive surviving sepsis guideline-directed vasopressor
therapy
• Nonadherence to repeat lactate levels when previous levels were above 2 mmol/L was 30%

This document is protected by the HCQIA 1986, 42 U.S.C. Sec. – 1102, et seq., and by Indiana Peer Review Act, Indiana Code Sec. 34-4-12.6-1, et
seq. All privileges or the immunities of these statutes are claimed.
SUMMARY
• Nearly two thirds of the patients treated with phenylephrine did not receive guideline recommended therapy prior
to the initiation of phenylephrine.
• Repeat lactate levels should be drawn when the initial lactate is above 2 mmol/L. Results showed that repeat
lactates were only drawn for 30% of the patients they were required in, indicating nonadherence to guidelines
• Based on the findings stated above, it is recommended that additional education can be given to increase the use
of the Surviving sepsis guideline recommended therapy prior to resorting to medications not recommended in the
guidelines.

ACTION
Action Power of Strategy Person Responsible
(see table below)
1. Provide education to providers and
pharmacists about the importance of following 1 Hannah
guideline recommended therapy

Error-Reduction Strategy Power (Leverage)

Fail-safes and constraints 10

Forcing Functions 9

This document is protected by the HCQIA 1986, 42 U.S.C. Sec. – 1102, et seq., and by Indiana Peer Review Act, Indiana Code Sec. 34-4-12.6-1, et
seq. All privileges or the immunities of these statutes are claimed.
 Automation and computerization 8
Standardization 6
Redundancies 5
Reminders and checklists 3
Rules and Policies 2
Suggestions to be more careful or
1
vigilant, Education

This document is protected by the HCQIA 1986, 42 U.S.C. Sec. – 1102, et seq., and by Indiana Peer Review Act, Indiana Code Sec. 34-4-12.6-1, et
seq. All privileges or the immunities of these statutes are claimed.