Amino Acid Infusion in Mothers Before and During Cesarean Delivery

March 14, 2019 updated by: Krishna Pokharel, B.P. Koirala Institute of Health Sciences

Intravenous Amino Acid Infusion in Mothers Before and During Cesarean Delivery: Effects on Maternal and Neonatal Temperature

Introduction: Intravenous infusion of amino acids during cesarean delivery in mothers and neonates improves neonatal growth. Amino acid before and during anesthesia also prevents hypothermia and associated untoward effects.

Method: After ethical approval, this prospective randomized double blind controlled study is being conducted in the university hospital of BPKIHS. Seventy six parturients (ASA 1 & 2) undergoing cesarean delivery without fetal distress, intrauterine growth retardation, congenital malformation or premature labor will be enrolled.

For a period starting from approximately one hour prior to spinal anesthesia, Group 1 and Group 2 patients will receive 200 ml of amino acid and lactated ringers solution respectively at 2 ml/kg/hr. The ambient operating room temperature will be maintained near 23º C. No heating methods will be applied apart from covering with a blanket.

Primary outcome measure will be neonatal rectal temperature at 0, 5 and 10 min after birth. Secondary outcome measures will be APGAR scores and suckling reflex in the newborn, change in rectal temperature relative to baseline and discomfort related to cold sensation in the mother and the occurrence of shivering both in the mother and newborn.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Review of literature:

Hypothermia is common during peri-operative period (1). It can lead to shivering (2), sympathetic stimulation (3), ischemic cardiac events (3), coagulation disturbances (4,5) delayed recovery from anesthesia (6,7), altered immune system with impaired wound healing (8,9) and prolonged hospitalization (9).

Amino acid infusion before and during surgery is known to prevent peri-operative hypothermia as a result of increased thermogenesis (10,11) without additional sympatho-adrenal activity (12). The mechanism is based on nutrient induced thermogenesis; i.e., nutrient intake, especially proteins and amino acids, stimulates resting energy expenditure and heat production (13). This effect is more pronounced during general anesthesia than neuraxial block (14). It has also been proved that amino acid infusion before and/or during anesthesia and surgery decreases intra-operative blood loss (15), improves peri-operative recovery (16) and shortens the duration of hospital stay (17).

The safety of intravenous amino acid infusion during cesarean delivery was long ago established (18,19).While maternal intravenous administration of amino-acids led to increased levels of amino acids in maternal venous blood and fetal umbilical cord blood plasma, there was no increase in fetal uptake of amino acids.

The safety of amino acid in the first day of life after delivery has also already been proved (20,21). It has been used to achieve positive protein balance in the immediate postoperative period in neonates undergoing abdominal surgery (20). Aggressive therapy of intravenous amino acid in preterm infants during 12 hrs to two weeks after birth enhanced their growth and improved their nutritional status during hospitalization (21).

Rationale of the study:

One way to prevent the development of hypothermia during anesthesia is to stimulate endogenous heat production. Energy expenditure increases after ingestion or infusion of nutrients. The amount of energy expended over baseline, or thermic effect of food mainly represents the energy cost of nutrient absorption, handling, and storage. Among the different nutrients, proteins elicit the largest increase in energy expenditure and heat production.

Previous studies have found that intravenous amino acid infusions exert enhanced thermogenic effects during general anesthesia (10) The mechanism behind this phenomenon is not fully understood, although nutrient intake stimulates energy expenditure, and hence heat production, in the awake state (13). The administration of proteins/amino acids in awake individuals results in an approximately 20% increase in whole-body heat content and a significant increase in body temperature (22,23).

Since amino acid transfer across the placenta depends upon its concentration in maternal blood (21,24), the investigators hypothesize that by increasing its concentration in the maternal blood, the amino acid level in newborn will be increased. The amino acid induced increased thermogenesis in the mother is likely to increase maternal temperature and thus fetal temperature. Also amino acids that have crossed the placenta may increase thermogenesis in the fetus, further enhancing neonatal temperature.

Research design and methodology:

After getting approval from the institutional research ethics committee and written informed consent, this prospective randomized double blind study was conducted in the University hospital of B P Koirala Institute of Health Sciences (BPKIHS). Parturients belonging to American Society of Anesthesiologists physical status I and II scheduled for elective cesarean delivery were enrolled. Pregnancy with fetal distress, intrauterine growth retardation, congenital malformation or premature labor were excluded.

With the help of computer generated random numbers, each consecutive eligible patients scheduled for cesarean delivery were assigned to one of the two groups to receive 200 ml of intravenous amino acid (Active drug) (n=38) or nutrient free standard ringers lactate solution (active comparator) (n=38) at 2 ml/kg/hr approximately one hour before spinal anesthesia. Amino acid solution used was a balanced mixture of 18 pure crystalline amino acids, eight of which are essential amino acids (Alamin SN ®, Albert D Limited, Kolkata, India).

On the pre-anesthetic visit one day prior to surgery, all the patients were explained about the nature of the study and the various questions to be asked during the study. Approximately 90 minutes prior to surgery, each patient was taken to the pre-operative room inside the operation theater. Heart rate, respiratory rate, rectal temperature and SpO2 were monitored continuously and non invasive blood pressure every five minutes. To maintain blinding, all the infusion bags were covered with an opaque plastic sheet and labelled as 'infusion bag' and hanged on the infusion stand near the patient by an anesthetist not involved in the management or data collection thereafter. Intravenous infusion of amino acid solution or ringer's solution was started approximately one hour prior to spinal anesthesia after recording the baseline vital parameters. Each patient received a total of 200 ml at 2 ml/kg/min. Both the patients and the assessor were unaware of the group assignment.

After one hour of infusion, each patient was transferred to the operating room. The ambient temperature of the operating room was maintained near 23°C. The monitoring of non invasive blood pressure, heart rate, respiratory rate, oxygen saturation (SpO2) and rectal temperature were continued at the same intervals. Spinal anesthesia was induced with 2 ml of 0.5% bupivacaine at L 3-4 inter-space applying aseptic precautions with the patient in the lateral position. After administration of spinal anesthesia, both groups received Ringers solution 15-20 ml/kg/hr maintained at ambient temperature via a separate venous access. All the patients were covered with a blanket, but no other heating methods were applied. Amino acid infusion were continued till the completion of 200 ml the solution contained in the infusion bag.

The maternal rectal temperature were recorded before infusion (baseline), prior to spinal block, at the time of delivery, at half an one hour after spinal block, and at the end of infusion of 200 ml of study solution. At the end of surgery, each mother was asked about her perception of cold and its related discomfort on a 0-2 subjective scale (0= No perception, 1= Tolerable perception, 2=Intolerable perception).

The rectal temperature and APGAR scores were assessed at 0, 5 and 10 minutes and suckling reflex at 10 minutes of the birth of baby. The occurrence of shivering and duration of hospital stay were noted for both the mother and baby.

Primary outcome parameters was the neonatal rectal temperature at 0, 5 and 10 minutes after birth. Secondary outcome parameters included neonatal APGAR scores at 0, 5 and 10 minutes after birth, the number of newborn having suckling reflex; number of neonates who developed shivering within 10 minutes after birth; change in maternal rectal temperature relative to baseline at various time points during study drug infusion, maternal temperature at the time of delivery during intraoperative period; number of mothers developing cold sensation related discomfort during the intra-operative period; number of mothers who developed shivering during intra-operative period.

Previous report showed that the mean rectal temperature of new born immediately after delivery following spinal anaesthesia was 37.7°C. (22) With the help of STATA, it was estimated that a sample size of 26 in each group could achieve a power of 95% to detect a difference of 0.5 °C (with common standard deviation of 0.5) in the outcome measure of new born rectal temperature, assuming type 1 error of 0.05.

For the secondary outcome, the sample size was calculated using online statistical calculator G power (R) version 3.0.1. Cohen d was used to calculate the effect size based on the findings of a previous study.(14) The mean final core temperature 90 min after induction of spinal anaesthesia was 35.8 (SEM 0.1)°C in the saline group and 36.6 (0.1)°C in the amino acid group.(14) It was estimated that a sample size of 34 in each group could achieve a power of 80% to detect an effect size of 0.69 in the outcome measure of maternal core body temperature, assuming type 1 error of 0.05. We enrolled 38 patients in each group to compensate for dropout cases and shifting from normality in data distribution.

Study Type

Interventional

Enrollment (Actual)

76

Phase

  • Not Applicable

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

  • Nepal
    • Koshi
      • Dharan, Koshi, Nepal, 56700
        • B P Koirala Institute of Health Sciences

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Parturients belonging to American Society of Anesthesiologists physical status I and II scheduled for elective cesarean delivery were enrolled.

Exclusion Criteria:

  • Pregnancy with fetal distress, intrauterine growth retardation, congenital malformation or premature labor were excluded.

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
Experimental: Amino acid
Intravenous infusion of amino acid solution started approximately one hour prior to spinal anaesthesia after recording the baseline vital parameters. Each patient in experimental group received a total of 200 ml at 2 ml/kg/min.
Drug: Amino acid solution
a balanced mixture of 18 pure crystalline amino acids, eight of which are essential amino acids
Other Names:
  • Alamin SN ®, Albert D Limited, Kolkata, India
Placebo Comparator: Ringer's Lactate solution
Intravenous infusion of Ringer's lactate solution started approximately one hour prior to spinal anaesthesia after recording the baseline vital parameters. Each patient in experimental group received a total of 200 ml at 2 ml/kg/min.
Drug: Ringer's lactate solution
200 ml of Ringer's lactate solution
Other Names:
  • RINGER LACTATE SOLUTION ALBERT DAVID

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
neonatal rectal temperature
Time Frame: 0 min after delivery
0 min after delivery
neonatal rectal temperature
Time Frame: 5 min after delivery
5 min after delivery
neonatal rectal temperature
Time Frame: 10 min after delivery
10 min after delivery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
APGAR score of newborn
Time Frame: 0 min, 5 min, 10 min after birth
0 min, 5 min, 10 min after birth
number of newborn with adequate suckling reflex
Time Frame: 10 min after birth
absent or present
10 min after birth
scale assessing the discomfort related to cold sensation in mother
Time Frame: intraoperative period during spinal anesthesia
0= No perception, 1= Tolerable perception, 2=Intolerable perception
intraoperative period during spinal anesthesia
number of mothers who developed shivering
Time Frame: intraoperative period during spinal anesthesia
intraoperative period during spinal anesthesia
length of hospital stay of mother
Time Frame: up to 72 hours
up to 72 hours
length of hospital stay of newborn
Time Frame: up to 72 hours
up to 72 hours
change in maternal rectal temperature compared to baseline
Time Frame: before infusion (baseline) and 1 hour
before infusion (baseline) and 1 hour
maternal rectal temperature
Time Frame: at the time of delivery during intraoperative period (usually within 30 minutes)
at the time of delivery during intraoperative period (usually within 30 minutes)
change in maternal rectal temperature compared to baseline
Time Frame: before infusion (baseline) and at one hour after spinal block
before infusion (baseline) and at one hour after spinal block
change in maternal rectal temperature compared to baseline
Time Frame: before infusion (baseline) and at the end of infusion of 200 ml of study solution
before infusion (baseline) and at the end of infusion of 200 ml of study solution
number of neonates who developed shivering
Time Frame: during the first 10 min after birth
during the first 10 min after birth

Collaborators and Investigators

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

Sponsor

B.P. Koirala Institute of Health Sciences

Investigators

  • Study Chair: Krishna Pokharel, MD, B.P. Koirala Institute of Health Sciences

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

June 1, 2013

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

October 4, 2015

First Submitted That Met QC Criteria

October 13, 2015

First Posted (Estimate)

October 14, 2015

Study Record Updates

Last Update Posted (Actual)

March 15, 2019

Last Update Submitted That Met QC Criteria

March 14, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 599/068/069

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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