Postoperative Delirium After Intraoperative Ephedrine Versus Norepinephrine

Postoperative Delirium After Intraoperative Ephedrine Versus Norepinephrine: a Retrospective TriNetX Database Study

This retrospective study aims to investigate the effects of norepinephrine compared to ephedrine, administered on the day of surgery, on the incidence of postoperative delirium.

Study Overview

• Status: Not yet recruiting
• Conditions: Postoperative Delirium (POD); Norepinephrine; Ephedrine
• Intervention / Treatment: Drug: Ephedrine; Drug: Norepinephrine

Detailed Description

This retrospective analysis will be conducted using data from the TriNetX US Collaborative Network. This study was designed to assess the impact of intraoperative norepinephrine versus intraoperative ephedrine use on postoperative delirium. Inclusion criteria includes patients who underwent surgery (CPT code 1003143) and were either administered ephedrine or norepinephrine on the day of surgery and did not receive both vasopressors on the day of surgery. Exclusion criteria exclude patients who underwent neurology and neuromuscular surgery, cardiac surgery, and cardiac procedures; patients who were administered epinephrine or dopamine on the day of surgery; patients who were administered ephedrine or norepinephrine at any time within the 7 days following the day of surgery to account for patients that might have required pressor infusions for other causes; or a prior history of disorientation (ICD-10 code R41.0) or unspecified dementia (F03).

Propensity score matching through TriNetX will be used to adjust for age, sex, race, BMI, and comorbidities including cerebrovascular disease (ICD-10 code I60-I69), chronic heart failure (I11.0), primary hypertension (I10, I11.9), chronic obstructive pulmonary disease (COPD) (J42, J43, J44, J47), asthma (J45), chronic kidney disease (CKD) (I12, I13), diabetes mellitus (E08-E13), depression (F32.A), schizoaffective disorders (F25), alcohol and drug abuse (F10.1, F10.2, Z71.4), smoking status (F17.2, F17.21), and history of antipsychotic (CN700) and benzodiazepine (C302) usage.

Independent t-tests and chi-squared tests will be used to compare postoperative delirium across the cohorts. To evaluate the relationship between norepinephrine and postoperative delirium versus ephedrine and postoperative delirium, risk differences, and risk ratios with 95% CIs will be calculated following propensity score matching. The TriNetX platform will be used for all analyses, with p < 0.05 representing statistical significance.

• Study Type: Observational
• Enrollment (Estimated): 10000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients within the TriNetX database.

Description

Ephedrine group:

Inclusion Criteria:

• underwent surgery (CPT code 1003143)
• administered ephedrine on the day of surgery

Exclusion Criteria:

• received both vasopressors (ephedrine and norepinephrine) on the day of surgery.
• patients who underwent neurology and neuromuscular surgery, cardiac surgery, and cardiac procedures
• patients who were administered epinephrine or dopamine on the day of surgery
• patients who were administered ephedrine or norepinephrine at any time within the 7 days following the day of surgery
• a prior history of disorientation (ICD-10 code R41.0) or unspecified dementia (F03)

Norepinephrine group:

Inclusion Criteria:

• underwent surgery (CPT code 1003143)
• administered norepinephrine on the day of surgery

Exclusion Criteria:

• received both vasopressors (ephedrine and norepinephrine) on the day of surgery.
• patients who underwent neurology and neuromuscular surgery, cardiac surgery, and cardiac procedures
• patients who were administered epinephrine or dopamine on the day of surgery
• patients who were administered ephedrine or norepinephrine at any time within the 7 days following the day of surgery
• a prior history of disorientation (ICD-10 code R41.0) or unspecified dementia (F03)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Ephedrine group; This group received ephedrine on the day of surgery.	Drug: Ephedrine; Received ephedrine the same day of surgery.
Norepinephrine group; This group received norepinephrine on the day of surgery.	Drug: Norepinephrine; Received norepinephrine the same day of surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative delirium	The outcome of postoperative delirium will be observed using the ICD-10 codes F05, R40, and R41 for delirium, somnolence, and disorientation, respectively.	Within 7 days following surgery.

Collaborators and Investigators

• Sponsor: Riverside University Health System Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): February 20, 2025
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: February 19, 2025
• First Submitted That Met QC Criteria: February 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 19, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Norepinephrine; Postoperative delirium; Ephedrine
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Emergence Delirium; Delirium; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Central Nervous System Stimulants; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine; Ephedrine
• Other Study ID Numbers: Ephedrine vs Norepinephrine

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We do not have an IPD in place at this time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No