Intramuscular Phenylephrine HCL for Prevention of Spinal Anesthesia Induced Hypotension

NCT ID: NCT05348980

Last Updated: 2022-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-01
• Study Completion Date: 2020-07-31

Brief Summary

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.

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.

Conditions

Hypotension; Anesthesia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Phenylephrine 4mg

Inj Phenylephrine HCL 04 mg as Group P4.

Group Type: ACTIVE_COMPARATOR

Phenylephrine Hydrochloride 4 mg

Intervention Type: DRUG

Intramuscular Phenylephrine HCL 04 mg were administered as prophylactic stat dose in Vastus lateralis muscle of thigh 05 minutes before giving spinal anesthesia.

Phenylephrine 8mg

Inj Phenylephrine HCL 08 mg as Group P8.

Group Type: ACTIVE_COMPARATOR

Phenylephrine Hydrochloride 8 mg

Intervention Type: DRUG

Intramuscular Phenylephrine HCL 08 mg were administered as prophylactic stat dose in Vastus lateralis muscle of thigh 05 minutes before giving spinal anesthesia.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Injection Synephrine (Atco Laboratories Ltd. Pakistan; Injection Synephrine (Atco Laboratories Ltd. Pakistan

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Rehman Medical Institute - RMI

OTHER

Sponsor Role: lead

Responsible Party

Mohammad Shafiq

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mohammad Shafiq, FCPS

Role: PRINCIPAL_INVESTIGATOR

Rehman Medical Institute

Locations

Rehman Medical Institute

Peshawar, Khyber Pakhtunkhwa, Pakistan

Countries

Pakistan

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Other Identifiers

RMI/RMI-REC/Approval/57

Identifier Type: -

Identifier Source: org_study_id