The safety of norepinephrine versus phenylephrine in the treatment of post-spinal hypotension in parturients undergoing cesarean section: A systematic review & meta-analysis

Alexandra Christine K. Lao

 

BACKGROUND

• By 2030 the global cesarean section rate will be nearing 30% with 38 million CS being performed worldwide. Majority of these cesarean sections are performed under spinal anesthesia.

• Spinal-induced hypotension has adverse effects on the fetus. Thus, it is often treated with phenylephrine. However, while it is an effective treatment for the hypotension, phenylephrine being an alpha agonist also results in bradycardia.

• Repeated doses of phenylephrine may cause prolonged as well as severe bradycardia.

• Phenylephrine-induced bradycardia has been shown to decrease cardiac output and, subsequently, uteroplacental perfusion. 

• Uteroplacental perfusion is the major determinant of fetal oxygenation and nutrient delivery, but due to its limited autoregulation, it is particularly dependent on maternal hemodynamics. Decreased perfusion has been associated with fetal acidosis, and lower APGAR scores.

• Thus, there is a potential advantage of norepinephrine as a safer alternative, in reducing maternal hypotension and improving neonatal outcomes. The combination of alpha and beta agonist activity is less likely to decrease maternal heart rate and cardiac output.

 

RESEARCH QUESTION

In parturients undergoing cesarean sections, does norepinephrine have a decreased incidence of bradycardia compared to phenylephrine for treating post-spinal hypotension?

 

OBJECTIVES

• Primarily, to conduct a systematic review and meta-analysis of randomized control trials to determine the safety profile of norepinephrine and phenylephrine.

• Safety would be defined as a lower incidence of bradycardia as found in the given studies. 

• Secondary outcomes would focus on hypotension as well as nausea, and vomiting

 

METHODS

 Step 1: Selection of studies

A systematic search was conducted in the following databases; PubMed, clinicaltrial.gov, and Cochrane Library. Two independent researchers screened the studies based on the ff. inclusion and exclusion criteria

• Inclusion Criteria: Elective cesarean delivery under subarachnoid block; the intervention involved the use of norepinephrine and phenylephrine to treat post-spinal hypotension, the article was peer-reviewed, and the study was a randomized controlled trial from August 2022-February 2024. 

• Exclusion Criteria: Emergency surgery, cesarean section performed under general anesthesia, non-RCT, and literature for which information on inclusion to the study could not be obtained and was inaccessible even after contacting the original authors.

Step 2: Data Extraction

Two authors (AKL and TDM) selected and independently reviewed each article included.  

Step 3: Risk of Bias

Two independent reviewers (AKL and TDM) critically appraised each trial using the Cochrane Risk of Bias tool.  A third reviewer (MC) was available to settle discrepancies in the appraisal process.