Just Accepted by Current Medical Research and Opinion
ORIGINAL ARTICLE
Retrospective comparison of ephedrine and phenylephrine for the treatment of spinal anesthesia induced hypotension in preeclamptic patients Unyime S. Ituk, Mary Cooter, Ashraf S. Habib Doi: 10.1185/03007995.2016.1159953 Abstract Objective: To compare neonatal acid base status in parturients who underwent ce‐ sarean delivery and received either ephedrine or phenylephrine boluses for the treatment of spinal anesthesia induced hypotension. Research Design and Methods: After institutional review board approval, the perio‐ perative database of the University of Iowa Hospitals and Clinics was used to identify all women diagnosed with preeclampsia and had cesarean delivery under spinal an‐ esthesia for the period January 1 2005 to July 31 2014. Data retrieved included patient demographics, indication for cesarean delivery, severity of preeclampsia, dose of vasopressor, neonatal umbilical artery pH and Apgar scores. Main Outcome Measures: Primary outcome was umbilical artery pH. Results: Data for 146 patients was included in the analysis. Ephedrine was used in fifty-seven patients (group E) and phe‐ nylephrine in eighty-nine (group PE) patients. The median umbilical artery pH was 7.30 (IQR 7.20 – 7.30) and 7.30 (IQR 7.20 – 7.30) in the ephedrine and phenylephrine groups respectively (P=0.41). Non-reassuring fetal heart trace was the only factor significantly associated with lower umbilical artery pH on multivariable regression analysis (β -0.09, P=0.002). Conclusions: We found no difference in neonatal umbilical artery pH between ephedrine and phenylephrine when used to treat spinal anesthesia induced hypotension during cesarean delivery in preeclamptic patients. Limitations of the study in‐ clude its retrospective single center design and the fact that the choice of vasopressor was not randomized.
© 2016 Taylor & Francis. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal's Just Accepted articles do not necessarily reflect those of Taylor & Francis (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.
ORIGINAL ARTICLE Retrospective comparison of ephedrine and phenylephrine for the treatment of spinal anesthesia induced hypotension in preeclamptic patients
Unyime S. Ituk Assistant Professor of Anesthesiology, Department of Anesthesia University of
D
Iowa, Iowa City, IA, USA
TE
Mary Cooter
Biostatistician, Department of Anesthesiology Duke University Medical Center,
EP
Durham, NC, USA
C
Ashraf S. Habib
AC
Professor, Department of Anesthesiology Duke University Medical Center, Durham,
ST
USA
Address for correspondence: Unyime Ituk, MBBS, FCARCSI, Department of Anesthesia
JU
University of Iowa, 200 Hawkins Drive, 6JCP, Iowa City, IA 52242 USA. [email protected]
Key words: Spinal anesthesia, hypotension, preeclampsia, cesarean section [Short Title: Ephedrine vs. Phenylephrine in preeclampsia]
Abstract Objective: To compare neonatal acid base status in parturients who underwent cesarean delivery and received either ephedrine or phenylephrine boluses for the treatment of spinal anesthesia induced hypotension. Research Design and Methods: After institutional review board approval, the perioperative database of the University of Iowa Hospitals and Clinics was used to identify all women diagnosed with preeclampsia and had cesarean delivery under spinal anesthesia
D
for the period January 1 2005 to July 31 2014. Data retrieved included patient
TE
demographics, indication for cesarean delivery, severity of preeclampsia, dose of vasopressor, neonatal umbilical artery pH and Apgar scores.
EP
Main Outcome Measures: Primary outcome was umbilical artery pH. Results: Data for 146 patients was included in the analysis. Ephedrine was used in fifty-
C
seven patients (group E) and phenylephrine in eighty-nine (group PE) patients.
AC
The median umbilical artery pH was 7.30 (IQR 7.20 – 7.30) and 7.30 (IQR 7.20 – 7.30) in the ephedrine and phenylephrine groups respectively (P=0.41). Non-reassuring fetal heart
ST
trace was the only factor significantly associated with lower umbilical artery pH on multivariable regression analysis (β -0.09, P=0.002).
JU
Conclusions: We found no difference in neonatal umbilical artery pH between ephedrine and phenylephrine when used to treat spinal anesthesia induced hypotension during cesarean delivery in preeclamptic patients. Limitations of the study include its retrospective single center design and the fact that the choice of vasopressor was not randomized.
Introduction Preeclampsia affects approximately 5% to 7% of pregnancies, resulting in significant maternal and neonatal morbidity and mortality1. In preeclamptic patients having cesarean delivery (CD), spinal anesthesia is a widely acceptable technique in the absence of an indwelling labor epidural catheter and if there is no contraindication to neuraxial anesthesia2. However the hemodynamic changes that can occur after spinal anesthesia can be detrimental to both the mother and fetus. While hypotension occurs less frequently
D
following spinal anesthesia in pre-eclamptic compared to non-pre-eclamptic patients,
TE
vasopressors are still required to treat spinal anesthesia induced hypotension in up to 25 % of patients3. Phenylephrine and ephedrine are the drugs commonly used in the management
EP
of hypotension in this patient population. The acid-base status of the neonate is an indicator of fetal well being immediately before delivery and therefore useful in the assessment of
C
uteroplacental perfusion and the impact of vasopressor therapy on the fetus4. It has also
AC
been suggested that low neonatal umbilical artery pH may be associated with poor neonatal outcomes5. Studies in healthy parturients have shown that ephedrine is associated with a
ST
lower umbilical artery pH compared to phenylephrine6, 7. This is likely due to the greater placental transfer of ephedrine, and increased fetal metabolic activity due to stimulation of
JU
fetal beta-adrenergic receptors8. The American Society of Anesthesiologists practice guidelines on obstetric anesthesia recommends that, in the absence of maternal bradycardia, phenylephrine may be a preferable agent because of improved fetal acid-base status9. Phenylephrine is therefore considered by many the vasopressor of choice in the obstetric patient10. However in parturients with preeclampsia there is no evidence from the literature to guide choice of vasopressor for managing spinal anesthesia induced hypotension. At our
institution a transition to phenylephrine as the first line agent for treatment of spinal anesthesia induced hypotension during CD occurred in 2010. We performed this study to assess the effect of ephedrine compared to phenylephrine on umbilical artery pH when used in the management of spinal anesthesia induced hypotension in preeclamptic patients.
Patients and Methods
D
After Institutional Review Board approval (Human Subjects Office University of Iowa
TE
IRB), we searched the perioperative database for the period January 1, 2005 through July 31, 2014 and identified all patients diagnosed with preeclampsia who had CD under spinal
EP
anesthesia. Data extracted from the electronic medical record included: maternal demographics, severity of preeclampsia, indication for CD, drug dosage for spinal
C
anesthesia, gestational age, birth weight, 1 minute and 5 minute Apgar score, dose of
AC
ephedrine or phenylephrine used for treating hypotension prior to delivery, umbilical artery pH, umbilical artery base excess, PCO2 and PO2 (neonatal umbilical cord blood gases are
ST
routinely measured for all operative deliveries at our institution).
JU
The urgency of CD was graded according to the classification by the Royal College of Obstetricians and Gynaecologists11. Category I is a clinical situation that presents immediate threat to life of the woman or fetus; category II indicates maternal or fetal compromise but no immediate threat to life; category III indicates need for early delivery but no maternal or fetal compromise; and category IV indicates CD at a time that suits the patient and maternity team.
Currently it is common practice at our institution to administer prophylactic phenylephrine infusion after spinal anesthesia in both healthy and preeclamptic parturients. However because we never had a similar infusion protocol with ephedrine we decided to include only patients that received boluses of vasopressors for the treatment of hypotension in our analysis. At our institution ephedrine is routinely administered as 5 mg boluses and phenylephrine as 100 mcg boluses. Patients who received both ephedrine and
D
phenylephrine for treatment of hypotension were excluded. We compared the dose of
TE
vasopressor between the groups using a conversion ratio of ephedrine 8 mg =
EP
phenylephrine 100 mcg12. Our primary outcome was neonatal umbilical artery pH.
Statistical Analysis
C
Mann-Whitney or t-tests were used for comparison of continuous variables, and chi-square
AC
or Fisher Exact tests were used for comparison of categorical variables between the groups. The variables compared in the univariate analysis included parturient characteristics,
ST
indications for CD, year of delivery and neonatal outcomes. Multivariable regression analysis was used to identify variables independently associated with lower umbilical artery
JU
pH. Variables with a P
ORIGINAL ARTICLE
Retrospective comparison of ephedrine and phenylephrine for the treatment of spinal anesthesia induced hypotension in preeclamptic patients Unyime S. Ituk, Mary Cooter, Ashraf S. Habib Doi: 10.1185/03007995.2016.1159953 Abstract Objective: To compare neonatal acid base status in parturients who underwent ce‐ sarean delivery and received either ephedrine or phenylephrine boluses for the treatment of spinal anesthesia induced hypotension. Research Design and Methods: After institutional review board approval, the perio‐ perative database of the University of Iowa Hospitals and Clinics was used to identify all women diagnosed with preeclampsia and had cesarean delivery under spinal an‐ esthesia for the period January 1 2005 to July 31 2014. Data retrieved included patient demographics, indication for cesarean delivery, severity of preeclampsia, dose of vasopressor, neonatal umbilical artery pH and Apgar scores. Main Outcome Measures: Primary outcome was umbilical artery pH. Results: Data for 146 patients was included in the analysis. Ephedrine was used in fifty-seven patients (group E) and phe‐ nylephrine in eighty-nine (group PE) patients. The median umbilical artery pH was 7.30 (IQR 7.20 – 7.30) and 7.30 (IQR 7.20 – 7.30) in the ephedrine and phenylephrine groups respectively (P=0.41). Non-reassuring fetal heart trace was the only factor significantly associated with lower umbilical artery pH on multivariable regression analysis (β -0.09, P=0.002). Conclusions: We found no difference in neonatal umbilical artery pH between ephedrine and phenylephrine when used to treat spinal anesthesia induced hypotension during cesarean delivery in preeclamptic patients. Limitations of the study in‐ clude its retrospective single center design and the fact that the choice of vasopressor was not randomized.
© 2016 Taylor & Francis. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal's Just Accepted articles do not necessarily reflect those of Taylor & Francis (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.
ORIGINAL ARTICLE Retrospective comparison of ephedrine and phenylephrine for the treatment of spinal anesthesia induced hypotension in preeclamptic patients
Unyime S. Ituk Assistant Professor of Anesthesiology, Department of Anesthesia University of
D
Iowa, Iowa City, IA, USA
TE
Mary Cooter
Biostatistician, Department of Anesthesiology Duke University Medical Center,
EP
Durham, NC, USA
C
Ashraf S. Habib
AC
Professor, Department of Anesthesiology Duke University Medical Center, Durham,
ST
USA
Address for correspondence: Unyime Ituk, MBBS, FCARCSI, Department of Anesthesia
JU
University of Iowa, 200 Hawkins Drive, 6JCP, Iowa City, IA 52242 USA. [email protected]
Key words: Spinal anesthesia, hypotension, preeclampsia, cesarean section [Short Title: Ephedrine vs. Phenylephrine in preeclampsia]
Abstract Objective: To compare neonatal acid base status in parturients who underwent cesarean delivery and received either ephedrine or phenylephrine boluses for the treatment of spinal anesthesia induced hypotension. Research Design and Methods: After institutional review board approval, the perioperative database of the University of Iowa Hospitals and Clinics was used to identify all women diagnosed with preeclampsia and had cesarean delivery under spinal anesthesia
D
for the period January 1 2005 to July 31 2014. Data retrieved included patient
TE
demographics, indication for cesarean delivery, severity of preeclampsia, dose of vasopressor, neonatal umbilical artery pH and Apgar scores.
EP
Main Outcome Measures: Primary outcome was umbilical artery pH. Results: Data for 146 patients was included in the analysis. Ephedrine was used in fifty-
C
seven patients (group E) and phenylephrine in eighty-nine (group PE) patients.
AC
The median umbilical artery pH was 7.30 (IQR 7.20 – 7.30) and 7.30 (IQR 7.20 – 7.30) in the ephedrine and phenylephrine groups respectively (P=0.41). Non-reassuring fetal heart
ST
trace was the only factor significantly associated with lower umbilical artery pH on multivariable regression analysis (β -0.09, P=0.002).
JU
Conclusions: We found no difference in neonatal umbilical artery pH between ephedrine and phenylephrine when used to treat spinal anesthesia induced hypotension during cesarean delivery in preeclamptic patients. Limitations of the study include its retrospective single center design and the fact that the choice of vasopressor was not randomized.
Introduction Preeclampsia affects approximately 5% to 7% of pregnancies, resulting in significant maternal and neonatal morbidity and mortality1. In preeclamptic patients having cesarean delivery (CD), spinal anesthesia is a widely acceptable technique in the absence of an indwelling labor epidural catheter and if there is no contraindication to neuraxial anesthesia2. However the hemodynamic changes that can occur after spinal anesthesia can be detrimental to both the mother and fetus. While hypotension occurs less frequently
D
following spinal anesthesia in pre-eclamptic compared to non-pre-eclamptic patients,
TE
vasopressors are still required to treat spinal anesthesia induced hypotension in up to 25 % of patients3. Phenylephrine and ephedrine are the drugs commonly used in the management
EP
of hypotension in this patient population. The acid-base status of the neonate is an indicator of fetal well being immediately before delivery and therefore useful in the assessment of
C
uteroplacental perfusion and the impact of vasopressor therapy on the fetus4. It has also
AC
been suggested that low neonatal umbilical artery pH may be associated with poor neonatal outcomes5. Studies in healthy parturients have shown that ephedrine is associated with a
ST
lower umbilical artery pH compared to phenylephrine6, 7. This is likely due to the greater placental transfer of ephedrine, and increased fetal metabolic activity due to stimulation of
JU
fetal beta-adrenergic receptors8. The American Society of Anesthesiologists practice guidelines on obstetric anesthesia recommends that, in the absence of maternal bradycardia, phenylephrine may be a preferable agent because of improved fetal acid-base status9. Phenylephrine is therefore considered by many the vasopressor of choice in the obstetric patient10. However in parturients with preeclampsia there is no evidence from the literature to guide choice of vasopressor for managing spinal anesthesia induced hypotension. At our
institution a transition to phenylephrine as the first line agent for treatment of spinal anesthesia induced hypotension during CD occurred in 2010. We performed this study to assess the effect of ephedrine compared to phenylephrine on umbilical artery pH when used in the management of spinal anesthesia induced hypotension in preeclamptic patients.
Patients and Methods
D
After Institutional Review Board approval (Human Subjects Office University of Iowa
TE
IRB), we searched the perioperative database for the period January 1, 2005 through July 31, 2014 and identified all patients diagnosed with preeclampsia who had CD under spinal
EP
anesthesia. Data extracted from the electronic medical record included: maternal demographics, severity of preeclampsia, indication for CD, drug dosage for spinal
C
anesthesia, gestational age, birth weight, 1 minute and 5 minute Apgar score, dose of
AC
ephedrine or phenylephrine used for treating hypotension prior to delivery, umbilical artery pH, umbilical artery base excess, PCO2 and PO2 (neonatal umbilical cord blood gases are
ST
routinely measured for all operative deliveries at our institution).
JU
The urgency of CD was graded according to the classification by the Royal College of Obstetricians and Gynaecologists11. Category I is a clinical situation that presents immediate threat to life of the woman or fetus; category II indicates maternal or fetal compromise but no immediate threat to life; category III indicates need for early delivery but no maternal or fetal compromise; and category IV indicates CD at a time that suits the patient and maternity team.
Currently it is common practice at our institution to administer prophylactic phenylephrine infusion after spinal anesthesia in both healthy and preeclamptic parturients. However because we never had a similar infusion protocol with ephedrine we decided to include only patients that received boluses of vasopressors for the treatment of hypotension in our analysis. At our institution ephedrine is routinely administered as 5 mg boluses and phenylephrine as 100 mcg boluses. Patients who received both ephedrine and
D
phenylephrine for treatment of hypotension were excluded. We compared the dose of
TE
vasopressor between the groups using a conversion ratio of ephedrine 8 mg =
EP
phenylephrine 100 mcg12. Our primary outcome was neonatal umbilical artery pH.
Statistical Analysis
C
Mann-Whitney or t-tests were used for comparison of continuous variables, and chi-square
AC
or Fisher Exact tests were used for comparison of categorical variables between the groups. The variables compared in the univariate analysis included parturient characteristics,
ST
indications for CD, year of delivery and neonatal outcomes. Multivariable regression analysis was used to identify variables independently associated with lower umbilical artery
JU
pH. Variables with a P
![[Comparison of metaraminol, phenylephrine and ephedrine in prophylaxis and treatment of hypotension in cesarean section under spinal anesthesia].](/assets/img/hold.png)
