Comparison of two Norepinephrine rescue bolus for Management of Post-spinal Hypotension during Cesarean Delivery: a randomized controlled trial

Yasmin S Hassabelnaby, Ahmed M Hasanin, Nada Adly, Maha M A Mostafa, Sherin Refaat, Eman Fouad, Mohamed Elsonbaty, Hazem A Hussein, Mohamed Mahmoud, Yaser M Abdelwahab, Ahmed Elsakka, Sarah M Amin, Yasmin S Hassabelnaby, Ahmed M Hasanin, Nada Adly, Maha M A Mostafa, Sherin Refaat, Eman Fouad, Mohamed Elsonbaty, Hazem A Hussein, Mohamed Mahmoud, Yaser M Abdelwahab, Ahmed Elsakka, Sarah M Amin

Abstract

Background: Data on the best norepinephrine bolus dose for management of hypotension are limited. The aim of this study was to compare the efficacy and safety of two norepinephrine bolus doses in the rescue management of maternal hypotension during cesarean delivery.

Methods: This randomized, controlled trial included mothers scheduled for cesarean delivery with spinal anesthesia with a prophylactic norepinephrine infusion. Following spinal anaesthesia administration, a participant was considered hypotensive if systolic blood pressure was ≤80% compared to the baseline reading. Participants were allocated to receive either 6 mcg or 10 mcg norepinephrine bolus for the management of hypotensive episodes. The hemodynamic response after administration of norepinephrine bolus was recorded. The episode was considered successfully managed if systolic blood pressure returned to within 80% from the baseline reading within 2 min after norepinephrine bolus administration, and did not drop again within 6 min after the norepinephrine bolus. The primary outcome was the incidence of successful management of the first hypotensive episode. Other outcomes included systolic blood pressure, heart rate, incidence of maternal bradycardia, and reactive hypertension.

Results: One hundred and ten mothers developed hypotensive episodes and received norepinephrine boluses for management. The number of successfully managed first hypotensive episodes was 50/57 (88%) in the 6 mcg-treated episodes and 45/53 (85%) in the 10 mcg-treated episodes (p = 0.78). Systolic blood pressure was comparable after administration of either bolus dose. Heart rate was lower after administration of 10 mcg bolus compared to 6 mcg bolus, without significant bradycardia requiring atropine administration. The incidence of reactive hypertension was comparable between both groups.

Conclusion: In mothers undergoing elective cesarean delivery under prophylactic norepinephrine infusion at 0.05 mcg/kg/min, there was no advantage to the use of 10 mcg norepinephrine bolus over 6 mcg norepinephrine bolus for the rescue management of first hypotensive episode. Neither of the 2 bolus doses reached a 100% success rate. The incidences of bradycardia and reactive hypertension were comparable between both norepinephrine doses.

Trial registration: At clinicaltrial.gov registry system on January 4, 2019 Clinical trial identifier: NCT03792906.

Keywords: Cesarean delivery; Hypotension; Norepinephrine; Spinal anesthesia.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
CONSORT chart showing patient recruitment
Fig. 2
Fig. 2
Systolic blood pressure. SBP: systolic blood pressure. Markers are means and error bars are standard deviations. *denotes statistical significance between both 6 mcg group and 10 mcg group. † denotes statistical significance compared to the pre-episodes reading within 6 mcg group, ‡ denotes statistical significance compared to the pre-episodes reading within 10 mcg group. Bonferroni test was used to adjust for multiple comparisons
Fig. 3
Fig. 3
Heart rate. Markers are means and error bars are standard deviations. *denotes statistical significance between both 6 mcg group and 10 mcg group. † denotes statistical significance compared to the pre-episodes reading within 6 mcg group, ‡ denotes statistical significance compared to the pre-episodes reading within 10 mcg group. Bonferroni test was used to adjust for multiple comparisons

References

    1. Kinsella SM, Carvalho B, Dyer RA, Fernando R, McDonnell N, Mercier FJ, et al. International consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia. Anaesthesia. 2018;73:71–92. doi: 10.1111/anae.14080.
    1. Hasanin A, Mokhtar AM, Badawy AA, Fouad R. Post-spinal anesthesia hypotension during cesarean delivery, a review article. Egypt J Anaesth. 2017;33:189–193. doi: 10.1016/j.egja.2017.03.003.
    1. Heesen M, Kölhr S, Rossaint R, Straube S. Prophylactic phenylephrine for caesarean section under spinal anaesthesia: systematic review and meta-analysis. Anaesthesia. 2014;69:143–165. . Accessed 6 Feb 2016.
    1. Ngan Kee WD, Lee SWY, Ng FF, Tan PE, Khaw KS. Randomized double-blinded comparison of norepinephrine and phenylephrine for maintenance of blood pressure during spinal anesthesia for cesarean delivery. Anesthesiology. 2015;122:736–745. doi: 10.1097/ALN.0000000000000601.
    1. Hasanin AM, Amin SM, Agiza NA, Elsayed MK, Refaat S, Hussein HA, et al. Norepinephrine infusion for preventing Postspinal anesthesia hypotension during cesarean delivery. Anesthesiology. 2019;130:55–62. doi: 10.1097/ALN.0000000000002483.
    1. Hasanin A, Amin S, Refaat S, Habib S, Zayed M, Abdelwahab Y, et al. Norepinephrine versus phenylephrine infusion for prophylaxis against post-spinal anaesthesia hypotension during elective caesarean delivery: a randomised controlled trial. Anaesth Crit Care Pain Med. 2019;38:601–607. doi: 10.1016/j.accpm.2019.03.005.
    1. Mercier FJ. Fluid loading for cesarean delivery under spinal anesthesia: have we studied all the options? Anesth Analg. 2011;113:677–680. doi: 10.1213/ANE.0b013e3182245af4.
    1. Sic Y, Young B, Kim U, Oh D, Yong E, Soo S, et al. A randomized , double - blind trial evaluating the efficacy of palonosetron with total intravenous anesthesia using propofol and remifentanil for the prevention of postoperative nausea and vomiting after gynecologic surgery. J Anesth. 2016;30:935–940. doi: 10.1007/s00540-016-2249-3.
    1. Onwochei DN, Ngan Kee WD, Fung L, Downey K, Ye XY, Carvalho JCA. Norepinephrine intermittent intravenous boluses to prevent hypotension during spinal anesthesia for cesarean delivery. Anesth Analg. 2017;125:212–218. doi: 10.1213/ANE.0000000000001846.
    1. Kee WDN. A random-allocation graded dose-response study of norepinephrine and phenylephrine for treating hypotension during spinal anesthesia for cesarean delivery. Anesthesiology. 2017;127:934–941. doi: 10.1097/ALN.0000000000001880.
    1. Mohta M, Dubey M, Malhotra RK, Tyagi A. Comparison of the potency of phenylephrine and norepinephrine bolus doses used to treat post-spinal hypotension during elective caesarean section. Int J Obstet Anesth. 2018;:[published Ahead of print]. doi:10.1016/j.ijoa.2018.12.002.
    1. Wei C, Qian J, Zhang Y, Chang X, Hu H, Xiao F. Prospective, randomised, double-blind, dose-finding study of norepinephrine for preventing spinal-induced hypotension during caesarean delivery under combined spinal-epidural anaesthesia. Eur J Anaesthesiol. 2020. 10.1097/EJA.0000000000001152.
    1. Hasanin A, Habib S, Abdelwahab Y, Elsayad M, Mostafa M, Zayed M, et al. Variable versus fixed-rate infusion of phenylephrine during cesarean delivery: a randomized controlled trial. BMC Anesthesiol. 2019;19:197. doi: 10.1186/s12871-019-0879-3.
    1. Ngan Kee WD, Khaw KS, Ng FF. Prevention of hypotension during spinal anesthesia for cesarean delivery: an effective technique using combination phenylephrine infusion and crystalloid cohydration. Anesthesiology. 2005;103:744–750. . Accessed 5 Mar 2016.
    1. Vallejo MC, Attaallah AF, Elzamzamy OM, Cifarelli DT, Phelps AL, Hobbs GR, et al. 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. 2017;29:18–25. doi: 10.1016/j.ijoa.2016.08.005.
    1. Hasanin A, Aiyad A, Elsakka A, Kamel A, Fouad R, Osman M, et al. Leg elevation decreases the incidence of post-spinal hypotension in cesarean section: a randomized controlled trial. BMC Anesthesiol. 2017;17:60. doi: 10.1186/s12871-017-0349-8.
    1. Hasanin A, Soryal R, Kaddah T, Raouf SA, Abdelwahab Y, Elshafaei K, et al. Hemodynamic effects of lateral tilt before and after spinal anesthesia during cesarean delivery: an observational study. BMC Anesthesiol. 2018;18:8. doi: 10.1186/s12871-018-0473-0.
    1. Fu F, Xiao F, Chen W, Yang M, Zhou Y, Ngan Kee WD, et al. A randomised double-blind dose-response study of weight-adjusted infusions of norepinephrine for preventing hypotension during combined spinal-epidural anaesthesia for caesarean delivery. Br J Anaesth. 2020. 10.1016/j.bja.2019.12.019.

Source: PubMed

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