Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03047109 |
| Other study ID # |
Phenylephrine Hypotension |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2/Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
February 7, 2017 |
| Est. completion date |
March 30, 2020 |
Study information
| Verified date |
October 2020 |
| Source |
Assiut University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Spinal anesthesia is widely used as the procedure of choice for cesarean delivery. In
comparison to epidural anesthesia it is faster, easier to perform, patients are more
comfortable, complication rates are lower, and it is more cost effective. Spinal anesthesia
is an accepted technique in elective cesarean sections. However, hypotension, resulted from
sympathectomy is a common problem, especially in pregnant women.
Spinal block causes peripheral vasodilation and venous pooling, which may result in maternal
hypotension. Maternal hypotension after spinal anesthesia for cesarean delivery, without
prophylactic measures, has a very high incidence (80%-100%). Even though highly investigated,
spinal induced hypotension remains a major concern, and it has been referred to as the "Holy
Grail" of obstetric anesthesia. The detrimental effects of the spinal induced hypotension are
maternal and fetal. Maternal effects are nausea, vomiting and dizziness. Hypotension results
in reduced uterine and intervillous blood flow with potential fetal hypoxia and acidosis.
Treatment and prevention of hypotension has been the subject of much investigation and
controversy. Prophylactic measures include: 1) left lateral tilt, 2) fluid preload, 3)
vasopressors,4) low dose spinal anesthesia. A 15° left lateral tilt is used routinely during
cesarean section, to prevent aorto-caval compression, however it is not sufficient as a sole
method. Left uterine displacement is achieved by tilting the operating table or by placing a
wedge under the woman's hip. Aorto-caval compression also may increase the spread of spinal
anesthesia. Among the non-pharmacological interventions studied to minimize the incidence of
hypotension sitting the patient up for up to 7 min after CSE anesthesia for cesarean section
reduced intraoperative ephedrine requirement without affecting the success of the spinal
anesthetic. In contrast, sitting up for 9 min resulted in the need for rescue epidural
anesthesia without additional benefit.
Phenylephrine Treatment of vascular failure in shock, shock-like states, drug-induced
hypotension or hypersensitivity; correction of paroxysmal supraventricular tachycardia;
prolongation of spinal anesthesia; vasoconstriction in regional analgesia; maintenance of
adequate level of BP during spinal and inhalation anesthesia. It has a number of important
attributes for treating spinal hypotension: (i) as an alpha-adrenergic agonist, its mechanism
of action directly addresses the decrease in systemic vascular resistance following spinal
anesthesia;(ii) phenylephrine has a faster onset of action compared with ephedrine; (iii)
ephedrine is associated with a five-fold increased risk of fetal acidosis; and (iv) ephedrine
is more likely to cross the placenta and increase concentrations of lactate, glucose, and
catecholamines in the fetal circulation compared with phenylephrine. However, phenylephrine
used alone may be accompanied by maternal bradycardia and does not benefit from widespread
clinical experience, as does ephedrine do. Thus, phenylephrine has not yet become popular,
particularly for prophylactic use. Clinical experience suggests that phenylephrine may be
useful in addition to ephedrine when the latter fails to correct hypotension.
Ephedrine sulphate is a potent sympathomimetic that stimulates both α and β receptors and has
clinical uses related to both actions. Its peripheral actions, which it owes in part to the
release of norepinephrine, simulate responses that are obtained when adrenergic nerves are
stimulated. These include an increase in blood pressure, stimulation of heart muscle,
constriction of arterioles.
Description:
Study design:
A prospective randomized clinical double-blind study using a computer generated randomization
will be conducted in a Women's Health Hospital, Assuit University. Neither the doctor
"investigator" nor the participant "parturient" will be aware of the group allocation or the
drug used. The study drugs will be prepared by one of the supervisor anesthetist (not
included in the procedure, observation or in data collection). The study will be carried on
60 parturient scheduled for elective cesarean section under spinal anesthesia. They will be
randomly allocated into two equal groups of 30 parturient each:
P group: Phenylephrine 30 µg/minute by syringe pump infusion for30 min. E group: Ephedrine 3
mg/ minute by syringe pump infusion for30 min. The study solutions (vasopressors) will be
prepared by another supervisor anesthetist and will be diluted with normal saline (Na Cl
0.9%) to the same total 50 ml volume in a syringe pump.
Pre-intervention Assessment:
All parturient will undergo full pre-anesthetic checkup (according to ASA guidelines)
including detailed history, physical and systemic examinations. They will be kept NOP (nil
per mouth) 6-8 hours for solids and 2 hours for water and clear fluids.
Parturient in the holding area:
Baseline monitoring readings of the maternal vital signs including HR, NIBP, SpO2 and RR.
Non-invasive Cardiac Output Monitoring:
The patients will positioned in the supine position, with uterine displacement to the left
lateral for several minutes and the electrodes of the noninvasive cardiac output monitor are
placed to measure cardiac output. Baseline reading of cardiac output will be recorded before
any intervention using NCCOM3 cardiodynamic monitor. . From this apparatus we will get HR,
EF, CO /CI, SVR
Uterine blood flow evaluation:
Baseline uterine blood flow will be recorded in the holding area and before any intervention
using SONO Ace R5 by the obstetric supervisor. Colour Doppler ultrasound will be used to
demonstrate the main ascending branches of left and right uterine arteries as they cross over
the hypogastric vessels just before they enter the uterus at the uterine-cervical junction.
The high pass filter was set at 125 Hz and the uterine artery will be obtained immediately
after the crossing of the hypogastric artery. The sample vol¬ume will be placed on the artery
with an angle of about 0°. After detection of blood flow and visu¬alization of the waveform
of the uterine artery, five blood flow indices will be automatically cal¬culated:
The pulsatility index (PI) (PI=PSV-EDV/TAMXV); The resistance index (RI) (RI=PSV-EDV/PSV);
The peak systolic velocity (PSV, units of cm/s); The end-diastolic velocity (EDV, units of
cm/s). TAMXV: Time averaged maximum velocity PSV: Peak systolic velocity. EDV: End-diastolic
velocity At least three consecutive correctly imaged blood flow velocity waveforms will be
analyzed; both right and left uterine arteries diameters will be measured on a perpendicular
B-mode view of the longitudinal vessel section at maxi¬mum magnification. Mean values of
bilateral uterine RI and PI will be used for statistical analysis.
Then intravenous cannula 18 G will be inserted into forearm vein under local anesthesia and
no premeditated drugs will be given to all women. Ringer's Lactate solution 10ml/kg will be
infused for all women participating in the study over 20-30-minutes, and then will be
transferred to the operating room.
Parturient in the operating room:
The previous monitoring data will be recorded again for the second time (including vital
data, maternal non-invasive cardiac output and uterine blood flow). Then the study solutions
will be started to infuse according to the previous description ( to prevent hypotension
mostly occur with spinal anesthesia during cesarean section).Then subarachnoid block will be
carried out under complete aseptic condition while the in the sitting position and the table
in the horizontal level using 25 G pencil point spinal needle, intrathecal block will be
performed at level of L 3-4 or L 4-5 vertebral interspaces, 12.5 mg (2.5 ml) of hyperbaric
bupivacaine 0.5% and 300 ug morphine sulphate will be injected intrathecally at the rate of
1ml/15 second (12) in all parturients for anesthesia. Immediately after end of injection of
drugs intrathecally, the parturient will be placed in the supine position with left uterine
displacement. Sensory block will be assessed using loss of sensation in response to cold
sensation using piece of ice along midclavicular line bilaterally every 2 minutes until reach
the level of T5 dermatome.
A third monitoring reading of the vital data, maternal non-invasive cardiac output and
uterine blood flow will be taken 15 minutes after spinal block and before the surgical
operation (cesarean section) starts.
Intra-operative Assessment:
After subarachnoid block all will be monitored for HR, NIBP, SpO2 and RR every 5 minutes till
the end of the surgery. All parturients will be continuously monitored intra-operatively for
any episodes of hypotension, hypertension, bradycardia or tachycardia. Hypotension: defined
as more than 20% decrease in maternal systolic blood pressure from the baseline. It will be
treated with intravenous crystalloid fluid bolus or drug boluses (1 ml) of the study drug
according the groupwhen needed. The total dose of drug boluses will be calculated when used.
Hypertension defined as more than 29% increase in maternal systolic blood pressure from the
baseline, if occurred, drug infusion will be stopped until the effect ends, then the infusion
will be started again. If relapse occur for 2 times, the drug infusion will be stopped and
the case will be excluded from the study.
Neonatal Evaluation:
Arterial blood sample will be collected from the fetal umbilical cord immediately through
double clamp segment after birth (about 10 cm of umbilical cord during clamping will be
sufficient to withdraw the sample). Analysis of the fetal umbilical arterial blood gas will
be performed. An umbilical blood PH of less than 7.2 will be considered fetal acidosis (19).
To assess the acid-base status and oxygenation of the fetus at delivery. Blood is drawn
separately with heparinized syringes from both an umbilical artery and umbilical vein from a
doubly clamped segment of the umbilical cord. If both umbilical vein and artery blood show
low PO2 (below 30 and 15 mmHg) and high pco2 (above 40 and 50 mmHg) , respectively
uteroplacental insufficiency was present.
All newborns will be evaluated by pediatrician regarding the APGAR score at 1st. and 5th
.minutes of birth.
Study outcomes Primary outcome
1- The difference in maternal cardiac output between the study groups Secondary outcomes
1. The difference in uterine blood flow indices by Doppler
2. The difference of intraoperative maternal vital singes.
3. The rate of occurrence of neonatal morbidity.
4. Complications or side effects of medications.
5. Parturient satisfaction.
Statistical analysis:
Data will be collected and will be analyzed using SPSS version 20 (SPSS, Inc., Chicago,
Illinios, USA). Normally distributed numerical data will be presented as mean +_SD, rang,
number and percentage. Numerical variables will be compared among the three groups using the
Kruskal-Wallis test and Mann-Whitney test. Categorical variables will be compared among the
three groups using the Chi-Square test and Fisher's exact test. P-value of less than 0.05
will be considered significant.
