COMPARATIVE STUDY BETWEEN NOREPINEPHRINE BOLUS AND NOREPINEPHRINE INFUSION IN PREVENTION OF POST-SPINAL HYPOTENSION IN CESAREAN SECTION

COMPARATIVE STUDY BETWEEN NOREPINEPHRINE BOLUS AND NOREPINEPHRINE INFUSION IN PREVENTION OF POST-SPINAL HYPOTENSION IN CESAREAN SECTION

By

Mohamed Abd Elgawad Abd Elhalim and Osama Allam Mandour

Department of Anesthesia and Intensive Care, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

ABSTRACT

Background: Post-spinal hypotension in patients of cesarean section (CS) remains    a common scenario in our practice with an incidence of hypotension is up to 71%. Norepinephrine is potent α adrenergic receptor and a weak β adrenergic agonist. It is suitable for maintaining blood pressure as phenylephrine and ephedrine in cesarean section.

Objectives: The aim of this work was to evaluate and compare the effects of prophylactic bolus norepinephrine and norepinephrine infusion on blood pressure during spinal anesthesia for cesarean section.

Patients and Methods: Eighty patients of American Society of Anesthesiology (ASA) physical status (I-II), aged (20-40) years old and undergoing to elective cesarean section who randomly classified into 2 equal groups: Group (I) received prophylactic bolus norepinephrine (10 μg) and Group (II) received prophylactic norepinephrine infusion (0.05 μg/kg/min). Fixed rate infusion and bolus dose of norepinephrine started immediately after spinal anesthesia.

Results: There were significant differences between group I and group II as regards maternal hemodynamic variables which was needed multiple doses of noradrenalin in group II. There were no significant differences in the intraoperative nausea and vomiting between groups. There were no significant differences between group I and group II as regards the fetal outcome.

Conclusion: Prophylactic bolus of norepinephrine and prophylactic norepinephrine infusion were effective for maintaining blood pressure of spinal anesthesia in cesarean section, and safe on maternal and fetal status. Norepinephrine infusion was superior to the intermittent boluses.

Key words: Spinal anesthesia; norepinephrine; hypotension; cesarean section.

INTRODUCTION

     Hypotension is a common side effect of spinal anesthesia for cesarean section. The incidence of post spinal hypotension in the cesarean section is up to 71% (Klohr et al., 2010). Hypotension is the physiological consequence of spinal block and can have a potentially deleterious maternal and fetal impact (De Giorgio et al., 2012). When post spinal anesthesia hypotension for cesarean section is severe and sustained, it may lead to serious complications as well as nausea and vomiting, impairment of the uterine blood flow with fetal hypoxia, acidosis and cardiovascular collapse (Cyna et al., 2006). Preventive measures of hypotension after spinal anesthesia included fluid loading, co-loading, leg wrapping, left lateral position, and vasopressors as phenylephrine and ephedrine (Loubert, 2012).

     Norepinephrine has α-adrenergic properties that can be used to prevention and treatment of spinal anesthesia induced vasodilation. Norepinephrine has mild and doses dependent β-adrenergic effects that might be beneficial to counteract pure vasoconstriction and a more effective vasopressor for maintaining blood pressure during spinal block (Hiltebrand et al., 2011).

     The aim of this work was to evaluate and compare the effects of prophylactic bolus norepinephrine and norepinephrine infusion on blood pressure during spinal anesthesia for cesarean section.

PATIENTS AND METHODS

     This is a prospective, single blinded, randomized and parallel study. The study was carried out in Al-Azhar University Hospitals from November 2017 to September 2018. After obtaining the Research and Ethics Committee approval in Al-Azhar University and written informed consents, eighty patients of (ASA) physical status (I-II), aged (20-40) years old and undergoing to elective cesarean section were included in this study. They were randomly classified into 2 equal groups:

Group I: Received prophylactic bolus norepinephrine (10 μg/ml).

Group II: Received prophylactic norepinephrine infusion (0.05 μg/kg/min).

The primary outcomes were incidence of hypotension episodes (SBP < 20% from baseline), hypertension episodes (SBP > 20% from baseline) and number of boluses of vasopressors used.

The secondary outcomes were nausea, vomiting, neonatal birth weight and neonatal outcome (measured Apgar scores at 1,5,10 minutes and umbilical cord blood pH) to evaluate the effect of noradrenalin bolus and noradrenalin infusion on neonatal outcome.

Inclusion criteria:

     Patients of ASA grade I or II, single fetus and full term pregnancy undergoing elective cesarean section.

Exclusion criteria:

     No single fetus, age less than 18 year, height less than 130 cm or more than 180 cm, weight less than 50 kg or more than 100 kg, contraindications to spinal anesthesia, allergy to drugs used in the study, placenta previa, diabetes mellitus, hypertension, contraindication of spinal anesthesia, allergy to local anesthesia, cardiovascular diseases, cerebrovasacular diseases, and chronic hypertension or pregnancy induced hypertension.

     Routine preoperative evaluation to patient's criteria was assessed for the study by details history taking, physical examination and the patient’s investigations in the anesthesia clinic before surgery by an anesthesiologist.

     Patients were fasted for 8 hours and had no premedication. Patients have two 18 gauge intravenous cannula. The baseline hemodynamic measurements (heart rate, oxygen saturation, electrocardiography and non-invasive arterial blood pressure) were recorded using monitoring system. External cardiotocography was used to monitor the fetal heart rate (HR). The skin was infiltrated with 2 ml lidocaine (1%). A 25 gauge spinal needle was inserted at L4–5 vertebral interspace. A mixture of 10 mg of hyperbaric bupivacaine (0.5%) and 25 μg fentanyl was injected at the subarachnoid space. At the start of intrathecal injection, intravenous (i.v.) fluid was started through a large bore i.v. cannula. There was other   a large bore intravenous cannula for norepinephrine infusion.

Statistical analysis:

     The statistical analysis was done by using Statistical Package for Social Science evaluation (SPSS) version 22.0 and Excel 2010. Comparison between groups by Student’s t test for parametric data and Mann–Whitney test for non-parametric data. Data was presented as median, numbers, proportions and means ± standard deviation. Comparison of proportions was performed using Chi square test. P value ≤ 0.05 was considered statistically significant and P value > 0.05 was considered statistically non-significant.

RESULTS

     Eighty patients undergoing to elective cesarean section who randomly classified into 2 equal groups: Group I received prophylactic bolus norepinephrine (10 μg) and Group II received prophylactic norepinephrine infusion (0.05 μg/kg/min).

      There were no statistically significant differences between two groups as regards demographic data (age (years), weight (kg), height (cm), ASA classification (I-II), duration of surgery, and indications of cesarean section (breech presentation, cephalopelvic disproportion, and previous cesarean section (Table 1).

Table (1): Demographic data between groups

- Data represented in means ± standard deviation (M ± SD) and numbers. P values > 0.05 are considered non-significant.

     There were significant differences between group I and group II which increase number of hypotension episodes, number of hypertension episodes, frequency of bradycardia, and number of boluses of vasopressors used in group I (Fig. 1).

Figure (1): Maternal hemodynamic variables (number of hypotension episodes, number of hypertension episodes and number of boluses of vasopressors used)

There were non-significant differences between group I and group II as regards incidence of intraoperative nausea and vomiting (Table 2).

Table (2): Incidence of intraoperative nausea and vomiting

-Data are expressed as numbers.

     There were non-significant differences between group I and group II as regards the fetal outcome: baseline fetal heart rate, birth weight, Apgar score, umbilical arterial blood gas and umbilical venous blood gas (Table 3).

Table (3): Fetal variables: The fetal outcome (baseline fetal heart rate, birth weight, Apgar score, umbilical arterial blood gas, and umbilical venous blood gas)

- Data represented in means ± standard deviation (M ± SD) and numbers. P values > 0.05 are considered non-significant.

DISCUSSION

     In this study, the effects of prophylactic bolus norepinephrine and norepinephrine infusion were assessed on blood pressure during spinal anesthesia for cesarean section. The ideal vasopressor used in post-spinal hypotension has inexpensive, reliable, quick in onset, easily available, favorably affecting maternal heart rate (HR) and minimizing detrimental effects upon the fetus and placental perfusion (Nag et al., 2015).

     The present study showed that non statistically significant difference between two groups as regards age, weight, height, ASA classification (I/II ), duration of surgery, and indications of cesarean section (breech presentation, cephalopelvic disproportion, and previous cesarean section.

     In our study, there were significant differences between groups as regards maternal hemodynamic variables (number of hypotension episodes, number of hypertension episodes, and number of boluses of vasopressors used).

     (Elnabtity and Selim, 2018) compared norepinephrine with ephedrine for spinal hypotension who found that norepinephrine was effective for maintain blood pressure in obstetric patients.

     (Ngan Kee et al., 2015) compared norepinephrine to phenylephrine in patients undergoing cesarean delivery under spinal anesthesia to maintain systolic blood pressure (SBP). They found that maternal cardiac output and heart rate (HR) were greater in women treated with norepinephrine compared with that treated with phenylephrine.

     Nausea and vomiting are common symptom of hypotension in the spinal anesthesia. There was non-significant difference between two groups as regards incidence of intraoperative nausea and vomiting were in agreement with (Elnabtity and Selim, 2018) who found that the incidence of maternal complications (nausea, vomiting, pruritus, headache, restlessness, and shivering) during the operation was comparable, and no statistically significant differences were detected between norepinephrine with ephedrine groups.

     In our study, there were no significant differences between group I and group II as regards the fetal outcome (baseline fetal heart rate, birth weight, Apgar score, umbilical arterial blood gas, and umbilical venous blood gas). This was in agreement with (Ngan Kee et al., 2015) compared the prophylactic continuous norepinephrine infusion (2.5 μg/min) with a bolus norepinephrine (5 μg/ml) in patients having spinal anesthesia for elective cesarean delivery.

     (Vallejo et al., 2017) study compared phenylephrine (0.1 μg/kg/min) with norepinephrine (0.05 μg/kg/min) using a fixed rate of infusion on parturient having cesarean delivery under spinal anesthesia who found that norepinephrine fixed rate of infusion has efficacy for preventing maternal hypotension.

     (El Shafei et al., 2015) compared norepinephrine with ephedrine to prevent of post spinal hypotension in coronary artery disease for knee arthroscopy. They found that norepinephrine is more effective than ephedrine in the maintenance of systolic blood pressure.

CONCLUSION

     Prophylactic bolus of norepinephrine and prophylactic norepinephrine infusion were effective for hypotension of spinal anesthesia in cesarean section and safe on maternal and fetal status. Norepinephrine infusion was superior to the intermittent boluses.

REFERENCES

1. Cyna AM, Andrew M, Emmett RS, Middleton P and Simmons SW (2006): Techniques for preventing hypotension during spinal anesthesia for cesarean section. Cochrane Database Syst Rev., 4:CD002251.

2. De Giorgio F, Grassi VM, Vetrugno G, d'Aloja E, Pascali VL and Arena V (2012): Supine hypotensive syndrome as the probable cause of both maternal and fetal death. J Forensic Sci., 57: 1646 1649.

3. Elnabtity AM and Selim MF (2018): Norepinephrine versus ephedrine to maintain arterial blood pressure during spinal anesthesia for cesarean delivery: A prospective double blinded trial. Anesth Essays Res., 12: 92-7.

4.  El-Shafei MM, El-Gendy HA and El-Fawy DM (2015): Norepinephrine versus ephedrine for the prevention of spinal anesthesia induced hypotension in coronary artery disease patients undergoing knee arthroscopy. Ain Shams J Anesthesiol., 8:424 8.

5. Hiltebrand LB, Koepfli E, Kimberger O, Sigurdsson GH and Brandt S (2011): Hypotension during fluid restricted abdominal surgery: effects of norepinephrine treatment on regional and microcirculatory blood flow in the intestinal tract. Anesthesiology, 114: 557-564.

6. Klohr S, Roth R, Hofmann T, Rossaint R and Heesen M (2010): Definitions of hypotension after spinal anesthesia for cesarean section: literature search and application to parturients. Acta Anesthesiol Scand., 54: 909-921.

7. Loubert C (2012): Fluid and vasopressor management for cesarean delivery under spinal anesthesia. Continuing professional development. Can J Anaesth., 59: 604 19.

8.  Nag DS, Samaddar DP, Chatterjee A, Kumar H and Dembla A (2015): Vasopressors in obstetric anesthesia: a current perspective. World J Clin Cases, 3: 58-64.

9. Ngan Kee WD, Lee SW, Ng FF, Tan PE and Khaw KS (2015): Randomized double blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology, 122: 736 45.

10. Vallejo MC, Attaallah AF, Elzamzamy OM, Cifarelli DT, Phelps AL and Hobbs GR (2017): An open label randomized controlled clinical trial for comparison of continuous phenylephrine versus norepinephrine infusion in prevention of spinal hypotension during cesarean delivery. Int J Obstet Anesth., 29:18 25.