Phenylephrine in Spinal Anesthesia in Preeclamptic Patients
| Status: | Completed |
|---|---|
| Conditions: | Cardiology, Women's Studies |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Reproductive |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 4/2/2016 |
| Start Date: | July 2006 |
| End Date: | June 2015 |
| Contact: | Robert J McCarthy, PharmD |
| Email: | r-mccarthy@northwestern.edu |
| Phone: | 312-926-9015 |
Phenylephrine Versus Ephedrine to Treat Spinal Anesthesia-Induced Hypotension in Preeclamptic Patients During Cesarean Delivery
Hypotension remains a common clinical problem after induction of spinal anesthesia for
cesarean delivery. Maternal hypotension has been associated with considerable morbidity
(maternal nausea and vomiting and fetal/neonatal acidemia). Traditionally, ephedrine has
been the vasopressor of choice because of concerns about phenylephrine's potential adverse
effect on uterine blood flow. This practice was based on animal studies which showed that
ephedrine maintained cardiac output and uterine blood flow, while direct acting
vasoconstrictors, e.g., phenylephrine, decreased uteroplacental perfusion. However, several
recent studies have demonstrated that phenylephrine has similar efficacy to ephedrine for
preventing and treating hypotension and may be associated with a lower incidence of fetal
acidosis. All of these studies have been performed in healthy patients undergoing elective
cesarean delivery.
Preeclampsia complicates 5-6% of all pregnancies and is a significant contributor to
maternal and fetal morbidity and mortality. Many preeclamptic patients require cesarean
delivery of the infant. These patients often have uteroplacental insufficiency. Given the
potential for significant hypotension after spinal anesthesia and its effect on an already
compromised fetus, prevention of (relative) hypotension in preeclamptic patients is
important. Spinal anesthesia in preeclamptic patients has been shown to have no adverse
neonatal outcomes as compared to epidural anesthesia when hypotension is treated adequately.
Due to problems related to management of the difficult airway and coagulopathy, both of
which are more common in preeclamptic women, spinal anesthesia may be the preferred regional
anesthesia technique. Recent studies have demonstrated that preeclamptic patients may
experience less hypotension after spinal anesthesia than their healthy counterparts. To our
knowledge, phenylephrine for the treatment of spinal anesthesia-induced hypotension has not
been studied in women with preeclampsia. The aim of our study is to compare intravenous
infusion regimens of phenylephrine versus ephedrine for the treatment of spinal anesthesia
induced hypotension in preeclamptic patients undergoing cesarean delivery. The primary
outcome variable is umbilical artery pH.
cesarean delivery. Maternal hypotension has been associated with considerable morbidity
(maternal nausea and vomiting and fetal/neonatal acidemia). Traditionally, ephedrine has
been the vasopressor of choice because of concerns about phenylephrine's potential adverse
effect on uterine blood flow. This practice was based on animal studies which showed that
ephedrine maintained cardiac output and uterine blood flow, while direct acting
vasoconstrictors, e.g., phenylephrine, decreased uteroplacental perfusion. However, several
recent studies have demonstrated that phenylephrine has similar efficacy to ephedrine for
preventing and treating hypotension and may be associated with a lower incidence of fetal
acidosis. All of these studies have been performed in healthy patients undergoing elective
cesarean delivery.
Preeclampsia complicates 5-6% of all pregnancies and is a significant contributor to
maternal and fetal morbidity and mortality. Many preeclamptic patients require cesarean
delivery of the infant. These patients often have uteroplacental insufficiency. Given the
potential for significant hypotension after spinal anesthesia and its effect on an already
compromised fetus, prevention of (relative) hypotension in preeclamptic patients is
important. Spinal anesthesia in preeclamptic patients has been shown to have no adverse
neonatal outcomes as compared to epidural anesthesia when hypotension is treated adequately.
Due to problems related to management of the difficult airway and coagulopathy, both of
which are more common in preeclamptic women, spinal anesthesia may be the preferred regional
anesthesia technique. Recent studies have demonstrated that preeclamptic patients may
experience less hypotension after spinal anesthesia than their healthy counterparts. To our
knowledge, phenylephrine for the treatment of spinal anesthesia-induced hypotension has not
been studied in women with preeclampsia. The aim of our study is to compare intravenous
infusion regimens of phenylephrine versus ephedrine for the treatment of spinal anesthesia
induced hypotension in preeclamptic patients undergoing cesarean delivery. The primary
outcome variable is umbilical artery pH.
The study will be approved by the Northwestern University Institutional Review Board.
Eligible women admitted to the Labor and Delivery Unit of Prentice Women's Hospital will be
approached for study participation immediately after the routine preanesthetic evaluation.
This usually occurs shortly after admission to the Labor and Delivery Unit. Women who agree
to participate will give written, informed consent at this time.
Preparation and initiation of spinal anesthesia will proceed according to routine practice
at our institution. A 16-gauge IV catheter will be inserted under local anesthesia in the
pre-operative labor and delivery suite. An IV infusion of lactated Ringer's solution will be
started at a minimal rate to maintain vein patency. Patients will be premedicated with
metoclopramide 10 mg and ranitidine 50 mg IV at least 30 minutes prior to procedure for
aspiration prophylaxis. Patients will be allowed to rest undisturbed for several minutes in
the left lateral tilt position, during which heart rate (HR) and systolic blood pressure
(SBP) will be taken every 1-2 minutes for at least 3 measurements. Baseline HR and SBP will
be the mean of these three recordings.
The subjects will be randomized according to a computer-generated randomization table to one
of two groups: Group 1 will receive a phenylephrine infusion and Group 2 will receive an
ephedrine infusion. All study medications will be prepared by an investigator not involved
in the care of the patient or collection of data. Both the anesthesiologist managing the
patient's anesthetic, as well as the patient, will be blinded to the study medication.
Upon arrival to the operating room, 30 mL of 0.3 M sodium citrate will be given orally and
standard monitoring will performed, including non-invasive BP, electrocardiography and pulse
oximetry. Oxygen will be given at 3 liter per minute by nasal cannula. Fetal heart rate will
be monitored by external cardiotocography until the time of surgical preparation. 500 mL of
lactated Ringer's solution will be given as a bolus concurrently with the start of the
spinal anesthesia procedure. Spinal anesthesia will be induced with patients in the sitting
position. After sterile skin preparation and draping, the skin will be infiltrated with
lidocaine, a 25 gauge Whitacre needle will be inserted at the L3-L4 vertebral interspace (±
one vertebral interspace) and bupivacaine 0.75%, 1.6 mL (12 mg), fentanyl 15 μg and morphine
150 μg will be injected intrathecally. Patients will be immediately placed supine with left
uterine displacement. SBP will be measured every 1 minute beginning 1 minute after spinal
injection for 10 minutes, then every 2.5 minutes for the remainder of the procedure.
Patients' hemodynamic data will be recorded throughout the procedure and printed at the end
of the surgery. Five minutes after spinal injection, the sensory level of anesthesia will be
assessed by loss of pinprick discrimination using von Frey hairs. If the patient fails to
obtain at least a T6 sensory level of anesthesia, that patient will be withdrawn from the
study. Preincision antibiotics, magnesium sulfate and uterotonic agents will be administered
intraoperatively per routine practice.
An unblinded investigator will prepare solutions of phenylephrine 100 μg per mL and
ephedrine 8000 μg per mL (potency phenylephrine:ephedrine 80:111). The investigator will
place 20 mL of the study medication into a syringe which will be given to the managing
anesthesiologist for infusion via a syringe pump. The infusion will be attached to the IV
cannula at the most distal. The infusion will be initiated immediately after completion of
the spinal injection at a rate of 1 mL per minute and continued for a minimum of two minutes
after which the infusion will either be stopped, continued or increased based on the SBP
measurement each minute. The goal will be to maintain SBP ≥ 80% baseline, but not > 160
mmHg. After each measurement of SBP, the infusion will be stopped if the SBP is greater than
80% baseline SBP, and the infusion will be continued or restarted if the SBP is
approximately equal to 80% baseline SBP.12 The infusion will be increased by 1 mL per minute
if the SBP measurement is less than 80% baseline. For the purpose of this study, we will
define hypotension as a decrease in SBP to < 80% of baseline.13 Each time there is a SBP
measurement demonstrating hypotension as defined above, the patient will receive a 1 mL IV
bolus of the study solution via the infusion pump and the infusion will be increased by 1 mL
per minute. The infusion and bolus protocol will be continued until delivery, after which
further management will be at the discretion of the managing anesthesiologist to maintain
SBP. If the baseline SBP > 160 mmHg, the infusion will not be started until the SBP
decreases to 160 mmHg. Infusion management will then proceed as described above.
The total volumes of the study solutions given by infusion and bolus up to the time delivery
will be recorded. Bradycardia (defined as HR < 60 bpm) associated with an SBP equal or
greater to baseline SBP will be treated by stopping the study solution and bradycardia
associated with SBP < 80% baseline will be treated with atropine intravenously. Hypotension
unresponsive to study medication will be treated with epinephrine (10 μg/mL) intravenous
boluses (1 mL) until correction of hypotension. Nausea or vomiting not associated with
hypotension will be treated with ondansetron 4 mg IV.
After delivery, oxytocin 10-20 IU will be given by slow IV infusion per routine. The
infant's 1 and 5 minute Apgar scores will be assessed by the nurse or pediatrician blinded
to patient group. The results of routine umbilical cord blood gas analysis will be recorded.
Eligible women admitted to the Labor and Delivery Unit of Prentice Women's Hospital will be
approached for study participation immediately after the routine preanesthetic evaluation.
This usually occurs shortly after admission to the Labor and Delivery Unit. Women who agree
to participate will give written, informed consent at this time.
Preparation and initiation of spinal anesthesia will proceed according to routine practice
at our institution. A 16-gauge IV catheter will be inserted under local anesthesia in the
pre-operative labor and delivery suite. An IV infusion of lactated Ringer's solution will be
started at a minimal rate to maintain vein patency. Patients will be premedicated with
metoclopramide 10 mg and ranitidine 50 mg IV at least 30 minutes prior to procedure for
aspiration prophylaxis. Patients will be allowed to rest undisturbed for several minutes in
the left lateral tilt position, during which heart rate (HR) and systolic blood pressure
(SBP) will be taken every 1-2 minutes for at least 3 measurements. Baseline HR and SBP will
be the mean of these three recordings.
The subjects will be randomized according to a computer-generated randomization table to one
of two groups: Group 1 will receive a phenylephrine infusion and Group 2 will receive an
ephedrine infusion. All study medications will be prepared by an investigator not involved
in the care of the patient or collection of data. Both the anesthesiologist managing the
patient's anesthetic, as well as the patient, will be blinded to the study medication.
Upon arrival to the operating room, 30 mL of 0.3 M sodium citrate will be given orally and
standard monitoring will performed, including non-invasive BP, electrocardiography and pulse
oximetry. Oxygen will be given at 3 liter per minute by nasal cannula. Fetal heart rate will
be monitored by external cardiotocography until the time of surgical preparation. 500 mL of
lactated Ringer's solution will be given as a bolus concurrently with the start of the
spinal anesthesia procedure. Spinal anesthesia will be induced with patients in the sitting
position. After sterile skin preparation and draping, the skin will be infiltrated with
lidocaine, a 25 gauge Whitacre needle will be inserted at the L3-L4 vertebral interspace (±
one vertebral interspace) and bupivacaine 0.75%, 1.6 mL (12 mg), fentanyl 15 μg and morphine
150 μg will be injected intrathecally. Patients will be immediately placed supine with left
uterine displacement. SBP will be measured every 1 minute beginning 1 minute after spinal
injection for 10 minutes, then every 2.5 minutes for the remainder of the procedure.
Patients' hemodynamic data will be recorded throughout the procedure and printed at the end
of the surgery. Five minutes after spinal injection, the sensory level of anesthesia will be
assessed by loss of pinprick discrimination using von Frey hairs. If the patient fails to
obtain at least a T6 sensory level of anesthesia, that patient will be withdrawn from the
study. Preincision antibiotics, magnesium sulfate and uterotonic agents will be administered
intraoperatively per routine practice.
An unblinded investigator will prepare solutions of phenylephrine 100 μg per mL and
ephedrine 8000 μg per mL (potency phenylephrine:ephedrine 80:111). The investigator will
place 20 mL of the study medication into a syringe which will be given to the managing
anesthesiologist for infusion via a syringe pump. The infusion will be attached to the IV
cannula at the most distal. The infusion will be initiated immediately after completion of
the spinal injection at a rate of 1 mL per minute and continued for a minimum of two minutes
after which the infusion will either be stopped, continued or increased based on the SBP
measurement each minute. The goal will be to maintain SBP ≥ 80% baseline, but not > 160
mmHg. After each measurement of SBP, the infusion will be stopped if the SBP is greater than
80% baseline SBP, and the infusion will be continued or restarted if the SBP is
approximately equal to 80% baseline SBP.12 The infusion will be increased by 1 mL per minute
if the SBP measurement is less than 80% baseline. For the purpose of this study, we will
define hypotension as a decrease in SBP to < 80% of baseline.13 Each time there is a SBP
measurement demonstrating hypotension as defined above, the patient will receive a 1 mL IV
bolus of the study solution via the infusion pump and the infusion will be increased by 1 mL
per minute. The infusion and bolus protocol will be continued until delivery, after which
further management will be at the discretion of the managing anesthesiologist to maintain
SBP. If the baseline SBP > 160 mmHg, the infusion will not be started until the SBP
decreases to 160 mmHg. Infusion management will then proceed as described above.
The total volumes of the study solutions given by infusion and bolus up to the time delivery
will be recorded. Bradycardia (defined as HR < 60 bpm) associated with an SBP equal or
greater to baseline SBP will be treated by stopping the study solution and bradycardia
associated with SBP < 80% baseline will be treated with atropine intravenously. Hypotension
unresponsive to study medication will be treated with epinephrine (10 μg/mL) intravenous
boluses (1 mL) until correction of hypotension. Nausea or vomiting not associated with
hypotension will be treated with ondansetron 4 mg IV.
After delivery, oxytocin 10-20 IU will be given by slow IV infusion per routine. The
infant's 1 and 5 minute Apgar scores will be assessed by the nurse or pediatrician blinded
to patient group. The results of routine umbilical cord blood gas analysis will be recorded.
Inclusion Criteria:
- ASA PS II - III women
- 18 years old and older
- scheduled for cesarean delivery (no trial of labor)
- eligible for spinal anesthesia
- diagnosis of preeclampsia
Exclusion Criteria:
- patients with failed trial of labor
- preexisting hypertension
- body mass index (BMI) ≥ 40 kg/m2
- resting heart rate < 60 bpm
- progression to eclampsia, > twin gestation
- known fetal anomalies
- contraindications to spinal anesthesia
- emergency procedure or refusal of consent
- failure to achieve a T6 level of anesthesia
- conversion to general anesthesia
We found this trial at
2
sites
Northwestern Memorial Hospital Northwestern Memorial is an academic medical center hospital where the patient comes...
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