Intramuscular Phenylephrine HCL for Prevention of Spinal Anesthesia Induced Hypotension
Condition: Hypotension; Anesthesia
MeSH terms: Hypotension
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Phenylephrine Hydrochloride 4 mg; Phenylephrine Hydrochloride 8 mg
Intervention type(s): Drug; Drug
Intervention description(s): Intramuscular Phenylephrine HCL 04 mg were administered as prophylactic stat dose in Vastus lateralis muscle of thigh 05 minutes before giving spinal anesthesia.; Intramuscular Phenylephrine HCL 08 mg were administered as prophylactic stat dose in Vastus lateralis muscle of thigh 05 minutes before giving spinal anesthesia.
Other intervention name(s): Injection Synephrine (Atco Laboratories Ltd. Pakistan; Injection Synephrine (Atco Laboratories Ltd. Pakistan
Intervention MeSH terms: Phenylephrine; Oxymetazoline; Synephrine
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study design was prospective double-blinded randomized parallel with allocation ratio of 1:1.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Cesarean section.