Is bolus norepinephrine dose as affective as ephedrine in preventing spinal anesthesia-induced hypotension in cesarean delivery?

Abstract

Objective: Spinal anesthesia is the preferred technique in cesarean delivery. Hypotension is the most common and concerning adverse effect (>80%) if no prophylaxis is given, which is major cause of maternal and fetal morbidity. Current literature suggests that vasopressor therapy is mainstay in prevention and management of spinal anesthesia-induced hypotension. Here, we aimed to compare the effects of prophylactic intravenous ephedrine and norepinephrine boluses on hypotension incidence in elective cesarean delivery under spinal anesthesia.
Materials and methods: The study included 62 term pregnant women (ASA II) with baseline systolic blood pressure (SBP) of 90-140 mmHg who were scheduled for elective cesarean section under spinal anesthesia. Ephedrine (10 mg, IV bolus) and norepinephrine (6 µg, IV bolus) were given simultaneously with spinal induction in group E and N, respectively. Hypotension was defined as SBP below 90% of baseline value (10% decrease from baseline) and respective agents in each group were given at same doses for treatment.
Results: Hypotension incidence was comparable in group E and N (64.5% vs. 74.2%, respectively). Severe hypotension (defined as SBP <80% of baseline) incidence was 32.3% in both groups. Tachycardia incidence and attacks were significantly higher in group E (p<0.01). Umbilical vein pH values was significantly higher in group E than group N (p<0.05). Fetal acidosis (defined as pH<7.20) was observed only in one newborn from group N.
Conclusion: Prophylactic ephedrine and norepinephrine IV boluses showed comparable efficacy in preventing and treating spinal anesthesia-induced hypotension. Both agents failed to decrease hypotension incidence.

Keywords

• Cesarean
• spinal anesthesia
• norepinephrine
• ephedrine
• hypotension

Sezaryen doğumlarda spinal anesteziye bağlı hipotansiyonu önlemede bolus doz norepinefrin efedrin kadar etkili midir?

Abstract

Amaç: Spinal anestezi, sezaryen doğumlarda tercih edilen bir anestezi tekniğidir. Profilaktik tedavi yapılmadığında en yaygın ve korkulan yan etkisi; %80'in üzerinde görülen, anne ve fetüs için önemli morbidite sebebi olan hipotansiyondur. Güncel literatür, spinal anestezi kaynaklı hipotansiyonun önlenmesi ve tedavisinde en önemli basamağın vazopressör desteği olduğunu bildirir. Bu çalışmada spinal anesteziyle yapılan elektif sezaryen doğumlarda, profilaktik verilen intravenöz (İV) bolus efedrin ve norepinefrinin hipotansiyon insidansına etkilerini karşılaştırmayı amaçladık.
Gereç ve yöntem: Bu çalışmaya spinal anesteziyle elektif sezaryen yapılacak, ASA II fiziksel durumunda, termde ve bazal sistolik kan basıncı değerleri (SKB) 90-140 mmHg aralığında olan 62 gebe dâhil edildi. Spinal anesteziyle eş zamanlı olarak, efedrin grubuna (Grup E) 10 mg İV bolus efedrin, norepinefrin grubuna (Grup N) 6 µg İV bolus norepinefrin profilaktik olarak uygulandı. SKB’nin, bazalin %90’ının altına düşmesi (bazal değerden %10 düşük olması) hipotansiyon olarak tanımlandı ve tedavi için her gruba kendi ilaçları aynı dozlarda verildi.
Bulgular: Hipotansiyon insidansı Grup E ve Grup N’de sırasıyla %64,5 ve %74,2 olarak benzerdi. SKB’nin bazalin %80’inin altına düşmesi (bazal değerden %20 düşük olması) olarak tanımlanan ciddi hipotansiyon insidansı, iki grupta da %32,3 ile daha düşük oranlarda bulundu. Taşikardi insidansı ve atakları, Grup E’de önemli ölçüde daha yüksekti (p<0,01). Umbilikal ven kan gazı pH değerleri, Grup E de Grup N’ye göre daha yüksekti (p0,05). Sadece Grup N’de ve tek bir yenidoğanda, pH’ın 7,20’den düşük olması şeklinde tanımlanan fetal asidoz görüldü.
Sonuç: İV profilaktik ve bolus olarak uyguladığımız efedrin ve norepinefrin spinal anesteziye bağlı hipotansiyonu önlemede ve tedavi etmede benzer etkinlikteydi. Her iki ajan da hipotansiyon insidansını azaltmada yeterli etkinlik gösteremedi.

Keywords

• Sezaryen
• spinal anestezi
• norepinefrin
• efedrin
• hipotansiyon

References

1. Lim G, Facco FL, Nathan N, Waters JH, Wong CA, Eltzschig HK. A review of the impact of obstetric anesthesia on maternal and neonatal outcomes. Anesthesiology. 2018 Jul 1;129(1):192–215. https://doi.org/10.1097/ALN.0000000000002182
2. Lim G, Facco FL, Nathan N, Waters JH, Wong CA, Eltzschig HK. A review of the impact of obstetric anesthesia on maternal and neonatal outcomes. Anesthesiology. 2018 Jul 1;129(1):192–215. https://doi.org/10.1097/ALN.0000000000002182
3. Lim G, Facco FL, Nathan N, Waters JH, Wong CA, Eltzschig HK. A review of the impact of obstetric anesthesia on maternal and neonatal outcomes. Anesthesiology. 2018 Jul 1;129(1):192–215. https://doi.org/10.1097/ALN.0000000000002182
4. Mercier FJ, Augè M, Hoffmann C, Fischer C, le Gouez A. Maternal hypotension during spinal anesthesia for caesarean delivery. Minerva Anestesiol. 2013 Jan;79(1):62–73.
5. Mercier FJ, Augè M, Hoffmann C, Fischer C, le Gouez A. Maternal hypotension during spinal anesthesia for caesarean delivery. Minerva Anestesiol. 2013 Jan;79(1):62–73.
6. Mercier FJ, Augè M, Hoffmann C, Fischer C, le Gouez A. Maternal hypotension during spinal anesthesia for caesarean delivery. Minerva Anestesiol. 2013 Jan;79(1):62–73.
7. Kinsella SM, Carvalho B, Dyer RA, et al. Guidelines international consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia for Obstetric Anesthesia and Perinatology Task. Anaesthesia. 2018;73:71–92. https://doi.org/10.1111/anae.14080
8. Kinsella SM, Carvalho B, Dyer RA, et al. Guidelines international consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia for Obstetric Anesthesia and Perinatology Task. Anaesthesia. 2018;73:71–92. https://doi.org/10.1111/anae.14080

9. Kinsella SM, Carvalho B, Dyer RA, et al. Guidelines international consensus statement on the management of hypotension with vasopressors during caesarean section under spinal anaesthesia for Obstetric Anesthesia and Perinatology Task. Anaesthesia. 2018;73:71–92. https://doi.org/10.1111/anae.14080
10. Nag DS, Samaddar DP, Chatterjee A, Kumar H, Dembla A. Vasopressors in obstetric anesthesia: a current perspective. World J Clin Cases. 2015 Jan 16;3(1):58–64. https://doi.org/10.12998/wjcc.v3.i1.58
11. Nag DS, Samaddar DP, Chatterjee A, Kumar H, Dembla A. Vasopressors in obstetric anesthesia: a current perspective. World J Clin Cases. 2015 Jan 16;3(1):58–64. https://doi.org/10.12998/wjcc.v3.i1.58
12. Nag DS, Samaddar DP, Chatterjee A, Kumar H, Dembla A. Vasopressors in obstetric anesthesia: a current perspective. World J Clin Cases. 2015 Jan 16;3(1):58–64. https://doi.org/10.12998/wjcc.v3.i1.58
13. Hess PE. What’s new in clinical obstetric anesthesia in 2015? Int J Obstet Anesth. 2017 Nov;32:54–63. https://doi.org/10.1016/j.ijoa.2017.03.008
14. Hess PE. What’s new in clinical obstetric anesthesia in 2015? Int J Obstet Anesth. 2017 Nov;32:54–63. https://doi.org/10.1016/j.ijoa.2017.03.008
15. Hess PE. What’s new in clinical obstetric anesthesia in 2015? Int J Obstet Anesth. 2017 Nov;32:54–63. https://doi.org/10.1016/j.ijoa.2017.03.008
16. Elnabtity AA, Selim M. Norepinephrine versus ephedrine to maintain arterial blood pressure during spinal anesthesia for cesarean delivery: a prospective double-blinded trial. Anesth Essays Res. 2018;12(1):92. https://doi.org/10.4103/aer.AER_204_17
17. Elnabtity AA, Selim M. Norepinephrine versus ephedrine to maintain arterial blood pressure during spinal anesthesia for cesarean delivery: a prospective double-blinded trial. Anesth Essays Res. 2018;12(1):92. https://doi.org/10.4103/aer.AER_204_17
18. Elnabtity AA, Selim M. Norepinephrine versus ephedrine to maintain arterial blood pressure during spinal anesthesia for cesarean delivery: a prospective double-blinded trial. Anesth Essays Res. 2018;12(1):92. https://doi.org/10.4103/aer.AER_204_17
19. Sharwood-Smith G, Drummond GB. Hypotension in obstetric spinal anaesthesia: a lesson from pre-eclampsia. Br J Anaesth. 2009 Mar;102(3):291–4. https://doi.org/10.1093/bja/aep003
20. Sharwood-Smith G, Drummond GB. Hypotension in obstetric spinal anaesthesia: a lesson from pre-eclampsia. Br J Anaesth. 2009 Mar;102(3):291–4. https://doi.org/10.1093/bja/aep003
21. Sharwood-Smith G, Drummond GB. Hypotension in obstetric spinal anaesthesia: a lesson from pre-eclampsia. Br J Anaesth. 2009 Mar;102(3):291–4. https://doi.org/10.1093/bja/aep003
22. Dyer RA, Reed AR, van Dyk D, Arcache MJ, Hodges O, Lombard CJ, et al. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology. 2009 Oct 1;111(4):753–65. https://doi.org/10.1097/ALN.0b013e3181b437e0
23. Dyer RA, Reed AR, van Dyk D, Arcache MJ, Hodges O, Lombard CJ, et al. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology. 2009 Oct 1;111(4):753–65. https://doi.org/10.1097/ALN.0b013e3181b437e0
24. Dyer RA, Reed AR, van Dyk D, Arcache MJ, Hodges O, Lombard CJ, et al. Hemodynamic effects of ephedrine, phenylephrine, and the coadministration of phenylephrine with oxytocin during spinal anesthesia for elective cesarean delivery. Anesthesiology. 2009 Oct 1;111(4):753–65. https://doi.org/10.1097/ALN.0b013e3181b437e0
25. Biricik E, Unlugenc H. Vasopressors for the treatment and prophylaxis of spinal induced hypotension during caesarean section. Turk J Anaesthesiol Reanim. 2021 Feb 3;49(1):3–10. https://doi.org/10.5152/TJAR.2020.70
26. Biricik E, Unlugenc H. Vasopressors for the treatment and prophylaxis of spinal induced hypotension during caesarean section. Turk J Anaesthesiol Reanim. 2021 Feb 3;49(1):3–10. https://doi.org/10.5152/TJAR.2020.70
27. Biricik E, Unlugenc H. Vasopressors for the treatment and prophylaxis of spinal induced hypotension during caesarean section. Turk J Anaesthesiol Reanim. 2021 Feb 3;49(1):3–10. https://doi.org/10.5152/TJAR.2020.70
28. Veeser M, Hofmann T, Roth R, Klöhr S, Rossaint R, Heesen M. Vasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. systematic review and cumulative meta-analysis. Acta Anaesthesiol Scand. 2012 Aug;56(7):810–6. https://doi.org/10.1111/j.1399-6576.2011.02646.x
29. Veeser M, Hofmann T, Roth R, Klöhr S, Rossaint R, Heesen M. Vasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. systematic review and cumulative meta-analysis. Acta Anaesthesiol Scand. 2012 Aug;56(7):810–6. https://doi.org/10.1111/j.1399-6576.2011.02646.x
30. Veeser M, Hofmann T, Roth R, Klöhr S, Rossaint R, Heesen M. Vasopressors for the management of hypotension after spinal anesthesia for elective caesarean section. systematic review and cumulative meta-analysis. Acta Anaesthesiol Scand. 2012 Aug;56(7):810–6. https://doi.org/10.1111/j.1399-6576.2011.02646.x
31. 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 Apr 1;122(4):736–45. https://doi.org/10.1097/ALN.0000000000000601
32. 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 Apr 1;122(4):736–45. https://doi.org/10.1097/ALN.0000000000000601
33. 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 Apr 1;122(4):736–45. https://doi.org/10.1097/ALN.0000000000000601
34. Ngan Kee WD. A random-allocation graded dose–response study of norepinephrine and phenylephrine for treating hypotension during spinal anesthesia for cesarean delivery. Anesthesiology. 2017 Dec 1;127(6):934–41. https://doi.org/10.1097/ALN.0000000000001880
35. Ngan Kee WD. A random-allocation graded dose–response study of norepinephrine and phenylephrine for treating hypotension during spinal anesthesia for cesarean delivery. Anesthesiology. 2017 Dec 1;127(6):934–41. https://doi.org/10.1097/ALN.0000000000001880
36. Ngan Kee WD. A random-allocation graded dose–response study of norepinephrine and phenylephrine for treating hypotension during spinal anesthesia for cesarean delivery. Anesthesiology. 2017 Dec 1;127(6):934–41. https://doi.org/10.1097/ALN.0000000000001880
37. Saravanan S, Kocarev M, Wilson RC, Watkins E, Columb MO, Lyons G. Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in caesarean section. Br J Anaesth. 2006 Jan;96(1):95–9. https://doi.org/10.1093/bja/aei265
38. Saravanan S, Kocarev M, Wilson RC, Watkins E, Columb MO, Lyons G. Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in caesarean section. Br J Anaesth. 2006 Jan;96(1):95–9. https://doi.org/10.1093/bja/aei265
39. Saravanan S, Kocarev M, Wilson RC, Watkins E, Columb MO, Lyons G. Equivalent dose of ephedrine and phenylephrine in the prevention of post-spinal hypotension in caesarean section. Br J Anaesth. 2006 Jan;96(1):95–9. https://doi.org/10.1093/bja/aei265
40. 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: a sequential allocation dose-finding study. Anesth Analg. 2017 Jul;125(1):212–8. https://doi.org/10.1213/ANE.0000000000001846
41. 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: a sequential allocation dose-finding study. Anesth Analg. 2017 Jul;125(1):212–8. https://doi.org/10.1213/ANE.0000000000001846
42. 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: a sequential allocation dose-finding study. Anesth Analg. 2017 Jul;125(1):212–8. https://doi.org/10.1213/ANE.0000000000001846
43. Lee A, Ngan Kee WD, Gin T. A dose-response meta-analysis of prophylactic intravenous ephedrine for the prevention of hypotension during spinal anesthesia for elective cesarean delivery. Anesth Analg. 2004 Feb;483–90. https://doi.org/10.1213/01.ANE.0000096183.49619.FC
44. Lee A, Ngan Kee WD, Gin T. A dose-response meta-analysis of prophylactic intravenous ephedrine for the prevention of hypotension during spinal anesthesia for elective cesarean delivery. Anesth Analg. 2004 Feb;483–90. https://doi.org/10.1213/01.ANE.0000096183.49619.FC
45. Lee A, Ngan Kee WD, Gin T. A dose-response meta-analysis of prophylactic intravenous ephedrine for the prevention of hypotension during spinal anesthesia for elective cesarean delivery. Anesth Analg. 2004 Feb;483–90. https://doi.org/10.1213/01.ANE.0000096183.49619.FC
46. Kol IO, Kaygusuz K, Gursoy S, et al. The effects of intravenous ephedrine during spinal anesthesia for cesarean delivery: a randomized controlled trial. J Korean Med Sci. 2009;24(5):883. https://doi.org/10.3346/jkms.2009.24.5.883
47. Kol IO, Kaygusuz K, Gursoy S, et al. The effects of intravenous ephedrine during spinal anesthesia for cesarean delivery: a randomized controlled trial. J Korean Med Sci. 2009;24(5):883. https://doi.org/10.3346/jkms.2009.24.5.883
48. Kol IO, Kaygusuz K, Gursoy S, et al. The effects of intravenous ephedrine during spinal anesthesia for cesarean delivery: a randomized controlled trial. J Korean Med Sci. 2009;24(5):883. https://doi.org/10.3346/jkms.2009.24.5.883
49. Fitzgerald JP, Fedoruk KA, Jadin SM, Carvalho B, Halpern SH. Prevention of hypotension after spinal anaesthesia for caesarean section: a systematic review and network meta‐analysis of randomised controlled trials. Anaesthesia. 2020 Jan 18;75(1):109–21. https://doi.org/10.1111/anae.14841
50. Fitzgerald JP, Fedoruk KA, Jadin SM, Carvalho B, Halpern SH. Prevention of hypotension after spinal anaesthesia for caesarean section: a systematic review and network meta‐analysis of randomised controlled trials. Anaesthesia. 2020 Jan 18;75(1):109–21. https://doi.org/10.1111/anae.14841
51. Fitzgerald JP, Fedoruk KA, Jadin SM, Carvalho B, Halpern SH. Prevention of hypotension after spinal anaesthesia for caesarean section: a systematic review and network meta‐analysis of randomised controlled trials. Anaesthesia. 2020 Jan 18;75(1):109–21. https://doi.org/10.1111/anae.14841
52. Xu S, Mao M, Zhang S, et al. A randomized double-blind study comparing prophylactic norepinephrine and ephedrine infusion for preventing maternal spinal hypotension during elective cesarean section uder spinal anesthesia. Medicine (Baltimore). 2019 Dec;98(51):e18311. https://doi.org/10.1097/MD.0000000000018311
53. Xu S, Mao M, Zhang S, et al. A randomized double-blind study comparing prophylactic norepinephrine and ephedrine infusion for preventing maternal spinal hypotension during elective cesarean section uder spinal anesthesia. Medicine (Baltimore). 2019 Dec;98(51):e18311. https://doi.org/10.1097/MD.0000000000018311
54. Xu S, Mao M, Zhang S, et al. A randomized double-blind study comparing prophylactic norepinephrine and ephedrine infusion for preventing maternal spinal hypotension during elective cesarean section uder spinal anesthesia. Medicine (Baltimore). 2019 Dec;98(51):e18311. https://doi.org/10.1097/MD.0000000000018311
55. Ngan Kee WD, Lee SWY, Ng FF, Khaw KS. Prophylactic norepinephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery. Anesth Analg. 2018 Jun;126(6):1989–94. https://doi.org/10.1213/ANE.0000000000002243
56. Ngan Kee WD, Lee SWY, Ng FF, Khaw KS. Prophylactic norepinephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery. Anesth Analg. 2018 Jun;126(6):1989–94. https://doi.org/10.1213/ANE.0000000000002243
57. Ngan Kee WD, Lee SWY, Ng FF, Khaw KS. Prophylactic norepinephrine infusion for preventing hypotension during spinal anesthesia for cesarean delivery. Anesth Analg. 2018 Jun;126(6):1989–94. https://doi.org/10.1213/ANE.0000000000002243
58. Cahill AG. Intrapartum fetal evaluation. In: Landon MB, Galan HL, Jauniaux ERM, Driscoll DA, Berghella V, Grobman WA, et al., editors. Gabbe’s obstetrics: normal and problem pregnancies. 8th ed. Philadelphia: Elsevier; 2021. p. 267–94.
59. Cahill AG. Intrapartum fetal evaluation. In: Landon MB, Galan HL, Jauniaux ERM, Driscoll DA, Berghella V, Grobman WA, et al., editors. Gabbe’s obstetrics: normal and problem pregnancies. 8th ed. Philadelphia: Elsevier; 2021. p. 267–94.
60. Cahill AG. Intrapartum fetal evaluation. In: Landon MB, Galan HL, Jauniaux ERM, Driscoll DA, Berghella V, Grobman WA, et al., editors. Gabbe’s obstetrics: normal and problem pregnancies. 8th ed. Philadelphia: Elsevier; 2021. p. 267–94.
61. Singh PM, Singh NP, Reschke M, Ngan Kee WD, Palanisamy A, Monks DT. Vasopressor drugs for the prevention and treatment of hypotension during neuraxial anaesthesia for caesarean delivery: a Bayesian network meta-analysis of fetal and maternal outcomes. Br J Anaesth. 2020 Mar;124(3):e95–107. https://doi.org/10.1016/j.bja.2019.09.045
62. Singh PM, Singh NP, Reschke M, Ngan Kee WD, Palanisamy A, Monks DT. Vasopressor drugs for the prevention and treatment of hypotension during neuraxial anaesthesia for caesarean delivery: a Bayesian network meta-analysis of fetal and maternal outcomes. Br J Anaesth. 2020 Mar;124(3):e95–107. https://doi.org/10.1016/j.bja.2019.09.045
63. Singh PM, Singh NP, Reschke M, Ngan Kee WD, Palanisamy A, Monks DT. Vasopressor drugs for the prevention and treatment of hypotension during neuraxial anaesthesia for caesarean delivery: a Bayesian network meta-analysis of fetal and maternal outcomes. Br J Anaesth. 2020 Mar;124(3):e95–107. https://doi.org/10.1016/j.bja.2019.09.045
64. Smiley RM, Blouin J-L, Negron M, Landau R. beta2-adrenoceptor genotype affects vasopressor requirements during spinal anesthesia for cesarean delivery. Anesthesiology. 2006 Apr 1;104(4):644–50. https://doi.org/10.1097/00000542-200604000-00006
65. Smiley RM, Blouin J-L, Negron M, Landau R. beta2-adrenoceptor genotype affects vasopressor requirements during spinal anesthesia for cesarean delivery. Anesthesiology. 2006 Apr 1;104(4):644–50. https://doi.org/10.1097/00000542-200604000-00006
66. Smiley RM, Blouin J-L, Negron M, Landau R. beta2-adrenoceptor genotype affects vasopressor requirements during spinal anesthesia for cesarean delivery. Anesthesiology. 2006 Apr 1;104(4):644–50. https://doi.org/10.1097/00000542-200604000-00006
67. Landau R, Liu S-K, Blouin J-L, Smiley RM, Ngan Kee WD. The effect of maternal and fetal β2-adrenoceptor and nitric oxide synthase genotype on vasopressor requirement and fetal acid-base status during spinal anesthesia for cesarean delivery. Anesth Analg. 2011 Jun;112(6):1432–7. https://doi.org/10.1213/ANE.0b013e3182179424
68. Landau R, Liu S-K, Blouin J-L, Smiley RM, Ngan Kee WD. The effect of maternal and fetal β2-adrenoceptor and nitric oxide synthase genotype on vasopressor requirement and fetal acid-base status during spinal anesthesia for cesarean delivery. Anesth Analg. 2011 Jun;112(6):1432–7. https://doi.org/10.1213/ANE.0b013e3182179424
69. Landau R, Liu S-K, Blouin J-L, Smiley RM, Ngan Kee WD. The effect of maternal and fetal β2-adrenoceptor and nitric oxide synthase genotype on vasopressor requirement and fetal acid-base status during spinal anesthesia for cesarean delivery. Anesth Analg. 2011 Jun;112(6):1432–7. https://doi.org/10.1213/ANE.0b013e3182179424