Intramuscular Phenylephrine HCL for Prevention of Spinal Anesthesia Induced Hypotension

April 21, 2022 updated by: Mohammad Shafiq, Rehman Medical Institute - RMI

Comparison of Two Different Doses of Intramuscular Phenylephrine HCL for Prevention of Spinal Anesthesia Induced Hypotension During Cesarean Section: A Prospective Randomized Double-blinded Parallel Study

Background: Spinal anesthesia (SA) is preferred over general anesthesia in Cesarean section (CS) due to its better safety profile but SA induced hypotension remains a big challenge for the clinical Anesthetist. Different methods including 15° left lateral table tilt, leftward uterine manual displacement, fluid pre-and co-loading have been used but drop in Systolic Blood Pressure (SBP) jeopardizing maternal and fetal well-being still occurs. Timely administered Phenylephrine HCL, an α-1 adrenergic agonist, is a recommended remedy.

Subjects and methods: Sixty parturients of American Society of Anaesthesiologists (ASA) physical status 1 and 2, scheduled for elective CS under SA were enrolled in this prospective double-blinded study and randomly divided into two equal groups, P4 and P8. They received intramuscular (IM) Phenylephrine HCL 04 mg and 08 mg respectively before SA. Spinal block up to T6 was achieved with 12.5 mg 0.5% Bupivacaine HCl heavy. The incidence and intensity of hypotension, rescue doses of Phenylephrine HCL and any adverse event, were recorded. Data collected was analyzed using Epi lnfo ™ version 7.2.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Introduction: World Health Organization (WHO) defines maternal death as a death while pregnant or within 42 days of the end of gestation, from any cause related to or aggravated by the pregnancy or its management (excluding accidental or incidental causes). In 2017 global Maternal Mortality Ratio (MMR) reported by United Nations (UN) is 211 deaths per 100,000 live births. MMR in Pakistan, with inter-provincial variability, is 186 deaths per 100,000 live births according to the latest Pakistan Maternal Mortality Survey (PMMS) report published in August, 2020 by United Nations Population Fund (UNFPA), a subsidiary organ of United Nations General Assembly.

CS requires general anesthesia, SA or epidural anesthesia; however, SA is preferred. SA is believed to be safe, though severe complications like profound hypotension compounded by aorto-caval compression might happen . World Health Organization (WHO) defines ideal CS rate below 10 to 15 %. According to 1990-91 and 2017-18 Pakistan Demographic and Health Survey data, rate of C-section has been raised from 3.2 % to 19.6 - 22.3 % . Higher rate of anesthesia and surgery in a developing country like Pakistan has a direct bearing on MMR, patient's morbidity, cost of medical services and siphoning scarce resources.

The first case of cardiac arrest occurring after SA was reported in 1940 and since then, the ability of SA to cause cardio-pulmonary arrest was considered. Hypotension and bradycardia are the most common side effects of SA. SA induced hypotension, which is a substantial clinical challenge, is caused by pharmacological sympathectomy. The incidence is reported around 80 %. Hypotension occurs despite fluid preload, left lateral uterine displacement and left lateral table tilt.

Duration and severity of hypotension is responsible for maternal ill effects like nausea/vomiting initially and later culminating to dyspnoea, apnea and circulatory arrest if poorly managed. Additionally there will be poor apgar score or even fetal demise depending upon the severity. Energetic use of strong vasopressors has been recommended. Phenylephrine HCL is considered to be the vasopressor of choice in parturients due to its propensity to cause less fetal acidosis. Phenylephrine HCL being an α-1adrenergic agonist counters the decrease in Systemic Vascular Resistance (SVR) induced by SA and can be administered by subcutaneous, intravenous and IM routes. Its onset and duration of action are 1-3 minutes and 5- 20 minutes respectively, when given intravenously (IV); and 10-20 minutes and an hour respectively when given IM. Clinically, 50-100 microgram boluses of Phenylephrine HCL is used intravenously to address hypotension. The investigators, in the current study exploited its lesser reported IM route.

Rationale: IM Phenylephrine HCL shortly before administering SA can prove a better option to prevent hypotension even for longer duration due to its slower absorption and can provide longer hemodynamic stability, lesser drop in fetal pH and apgar score.

Objectives: The primary objective of the study was to determine appropriate dose of IM Phenylephrine HCL in preventing hypotension due to SA administered for CS in ASA 1 and 2 parturients. Secondary objectives were to determine the need for total rescue doses of Phenylephrine HCL, measure drop in SBP in the two trial groups; and observe any side effects associated with IM injection of Phenylephrine HCL.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
    • Khyber Pakhtunkhwa
      • Peshawar, Khyber Pakhtunkhwa, Pakistan, 25000
        • Rehman Medical Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • All pregnant ladies of American Society of Anesthesiologists (ASA) physical status 1 or 2 with
  • Singleton Pregnancy,
  • Full term pregnancy, and
  • Admitted for elective CS

Exclusion Criteria:

All those participants having;

  • Blood pressure ≥140/90 mm of Hg,
  • ASA 3 or above status,
  • Contraindication to spinal anesthesia
  • Fetal anomalies/
  • Abnormal placentae
  • Refusal to consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Phenylephrine 4mg
Inj Phenylephrine HCL 04 mg as Group P4.
Drug: Phenylephrine Hydrochloride 4 mg
Intramuscular Phenylephrine HCL 04 mg were administered as prophylactic stat dose in Vastus lateralis muscle of thigh 05 minutes before giving spinal anesthesia.
Other Names:
  • Injection Synephrine (Atco Laboratories Ltd. Pakistan
Active Comparator: Phenylephrine 8mg
Inj Phenylephrine HCL 08 mg as Group P8.
Drug: Phenylephrine Hydrochloride 8 mg
Intramuscular Phenylephrine HCL 08 mg were administered as prophylactic stat dose in Vastus lateralis muscle of thigh 05 minutes before giving spinal anesthesia.
Other Names:
  • Injection Synephrine (Atco Laboratories Ltd. Pakistan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of hypotension in both groups
Time Frame: One and half hour post spinal anesthesia

The primary outcome is to find incidence of hypotension in each group P4 and P8 i.e. number of participants who develop hypotension in the relevant group multiplied by 100.

Incidence= number of participants who develop hypotension/ total participants in the group *100.

Hypotension is defined as a decrease of more than 20 % from baseline systolic blood pressure measured through non-invasive method.
One and half hour post spinal anesthesia

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To find the rescue dose/ doses of intravenous Phenylephrine HCL.
Time Frame: One and half hour post spinal anesthesia
To find the rescue dose/ doses of intravenous Phenylephrine in the two groups P4 and P8.
One and half hour post spinal anesthesia
Onset of hypotension
Time Frame: Half hour/ 30 minutes post spinal anesthesia
Determine the onset of hypotension in the two groups P4 and P8 (keeping starting time 0 minute at the administration of intrathecal hyperbaric Bupivacaine).
Half hour/ 30 minutes post spinal anesthesia
Adverse events associated with any groups
Time Frame: One and half hour post spinal anesthesia
Record any adverse event associated with any groups e.g. bradycardia, hypotension, Nausea, Vomiting, Hypertension, Cardiac arrest.
One and half hour post spinal anesthesia
Neonatal APGAR Score
Time Frame: 5 minutes post delivery

Neonatal APGAR (Appearance, Pulse, Grimace response, Activity, and Respiration)Score from 0 - 10 will be measured at 01 and 05 minutes for each neonate delivered. The higher score is considered good i.e. 10 while lower score is considered bad/ worse e.g. 0 -3.

The Apgar score measures five things to check a baby's health. Each is scored on a scale of 0 to 2, with 2 being the best score:

Appearance (skin color) Pulse (heart rate) Grimace response (reflexes) Activity (muscle tone) Respiration (breathing rate and effort)
5 minutes post delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rehman Medical Institute - RMI

Investigators

  • Principal Investigator: Mohammad Shafiq, FCPS, Rehman Medical Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2020

Primary Completion (Actual)

July 31, 2020

Study Completion (Actual)

July 31, 2020

Study Registration Dates

First Submitted

April 4, 2022

First Submitted That Met QC Criteria

April 21, 2022

First Posted (Actual)

April 27, 2022

Study Record Updates

Last Update Posted (Actual)

April 27, 2022

Last Update Submitted That Met QC Criteria

April 21, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RMI/RMI-REC/Approval/57

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data including clinical and demographic characteristics, not affecting patient's confidentiality, will be shared.

IPD Sharing Time Frame

April, 2022 to April, 2025.

IPD Sharing Access Criteria

IPD will be shared on inter institutional request basis.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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