The Efficacy and Safety of Norepinephrine and Its Feasibility as a Replacement for Phenylephrine to Manage Maternal Hypotension during Elective Cesarean Delivery under Spinal Anesthesia
Group NE1 (n=95), 0.025 μg/kg/min; NE2 (n=93), 0.05 μg/kg/min; NE3 (n=96), 0.75 μg/kg/min; followed with an initial bolus of NE 5 μg given post spinal anesthesia
SBP was higher with NE2/NE3 compared to NE1∗ Frequency of post-spinal hypotension: NE1 > NE2/NE3, 42.1%, 24.7%, and 26.0%, respectively∗ Frequency of severe hypotension, intraoperative hypertension, and postdelivery hypotension: ns
HR was lower in NE2/NE3 compared to NE1∗ Frequency of bradycardia requiring atropine, ns
Group NE (n=56) and group PE (n=56), NE bolus 6 μg vs. PE 100 μg whenever SBP lower than baseline, ephedrine 10 mg is given when SBP < 80% baseline + HR < 60bpm or SBP < 80% baseline for 2 consecutive readings
Incidence of hypotension, hypertension, and tachycardia: ns Need for NE and PE bolus: ns Need for rescue ephedrine bolus: 7.2% vs. 21.4%∗
Incidence of bradycardia: group NE < group PE, 6 (10.9%) vs 21 (37.5%)∗ Incidence of > 2 episodes of bradycardia: group NE < group PE, 2(3.6%) vs 11(19.6%)∗
N/A
Proportion of need for ephedrine: group NE < group PE, 7.2% vs. 21.4%∗ Vasopressor bolus required: 9 6-14 for NE vs. 8 5.5-10.5 for PE, ns
Group NE1 (n=53), manually controlled variable rate infusion, 0-5 μg/min for SBP near baseline Group NE2 (n=54), bolus 5 μg whenever SBP < 80% baseline
Incidence of hypotension: group NE1 < NE2, 9 (17%) vs 35 (66%)∗ AUC of SBP over time: group NE1 > NE2, 110.9 ± 8.3 vs 101.9 ± 9.4 mmHg∗
Incidence of bradycardia: 4 (7.5%) vs 4 (7.4%), ns AUC of HR over time: group NE1 < NE2, 82.2 ± 10.4 vs 88.2 ± 12.1 mmHg∗
CO: 6.85 ± 1.37 for group NE1 vs 6.42 ± 1.31 L/min for group NE2, ns
Total dose: group NE1 > NE2, 61.0 (47.0-72.5) vs 5.0 (0-18.1) μg Median rate: group NE1 > NE2, 2.22 (1.87-2.57) vs 0.28 (1.87-2.57) μg/min
MDPE: group NE1 < NE2, -2.99 (-6.36 to 0.29) vs -11.15 (-14.77 to -7.65)∗ MDAPE: group NE1 < NE2, 4.97 (3.81 to 6.74) vs 11.33 (7.86 to 14.99)∗ Wobble, 3.13 (2.51 to 3.76) vs 3.32 (2.45 to 5.00), ns
Group NE1 (n=29), 5 μg/kg/h; NE2 (n=30), 10 μg/kg/h; NE3 (n=28), 15 μg/kg/h; control group (n=30), saline infusion; rescue bolus 10 μg for SBP < 80 % baseline or < 90 mmHg
Incidence of hypotension: control group > NE1, NE2, NE3, 86.7, 37.9, 20, 25%, respectively∗ Incidence of hypertension: control group < NE1/NE2 < NE3, 10, 41.4, 36.6, and 75%, respectively∗
Incidence of bradycardia: 0, 3.4, 3.3, 10.7 %, ns HR: ns among groups
CO, SVR: ns
Total dose: control group < NE1 < NE2, NE3, 23 ± 20, 186.9 ± 79.6, 375.8 ± 137.3, 479.1 ± 243.8μg, respectively∗
Group NE (n=43), 0.05 μg/kg/min; group PE (n=38), 0.1 μg/kg/min; for SBP with 100-120% of baseline, rescue bolus PE 100 μg for hypotension (SBP < baseline) or rescue ephedrine 5 mg for hypotension + bradycardia (HR < 60 bpm)
Proportion of vasopressor requirement: 21 (48.8%) for group NE and 25 (65.8%) for group PE, ns Requirement for PE rescue bolus: 20 (46.5%) for group NE and 20 (52.6%) for group PE, ns Requirement for ephedrine rescue bolus: group NE < PE, 1 (2.3%), 9 (23.7%)∗ Incidence of hypertension: 1 (2.6%) vs 2 (4.7%), ns
Incidence of bradycardia: 8 (18.6%) for group NE and 9 (23.7%) for group PE, ns
CO, CI, SV, SVR: ns
Median total rescue PE dose: 100 0-700 for group NE and 50 0-1000μg for group PE, ns Median total rescue ephedrine dose: 0 0-30 for group NE and 0 0-85 mg for group PE, ns
Bolus NE 3 (n=6), 4 (n=2), 5 (n=9), 6 (n=20), 7 μg (n=3) to rescue first episode of hypotension
ED90 of NE 5.49 μg (95%CI 5.15-5.83) using truncated Dixon and Mood method; 5.80 μg (95% CI 5.01-6.59) using the isotonic regression method Hypotension incidence: 6 (15%), of which 5 (83.3%) with NE < 6μg; Incidence of hypertension: 4 (10%)
NE bolus 4, 5, 6, 8, 10, 12 μg vs. PE 60, 80, 100, 120, 160, 200 μg (n=15 for each dose group) for first episode of hypotension
ED50 for NE and PE is 10 μg (95%CI, 6-17μg), 137 μg (95% CI, 79 -236μg) ED90 for NE and PE is 18 μg (95%CI, 5-63μg), 239 μg (95% CI, 66-869μg) Potency ratio of NE compared to PE: 13.1 (95% CI, 10.4- 15.8)
NE 0-5 μg/min (n=49) vs. PE 0-100μg/min (n=52) for SBP near baseline with computer designed algorithm
Incidence of hypotension: 4(8.2%) for group NE, 4(7.7%) for group PE, ns Incidence of hypertension: 4 (8.2%) for group NE, 9 (17.3%) for group PE, ns
Incidence of bradycardia: 9 (18.4%) for group NE, 29 (55.8%) for group PE∗
N/A
Total vasopressor volume: 10.4 9.5-14.1, 14.3 9.9-16.9 ml, ns
MDPE (%): group NE < PE, 0.75 [-1.56 to 2.52] vs. 2.61 [0.83 to 4.57]∗ MDAPE (%): group NE < PE, 3.79 [2.82 to 5.17] vs. 4.70 [3.23 to 6.57]∗ Wobble (%): 2.85 [2.07 to 3.92] vs. 3.39 [2.62 to 4.90]∗ Divergence (% /min): ns
NE 0-5 μg/min (n=49) vs. PE 0-100μg/min (n=52) for SBP near baseline with computer designed algorithm
AUC of SBP over time: ns
AUC of HR over time: group NE > PE∗
AUC of CO: group NE > PE∗ AUC of SV: ns AUC of SVR: group NE < PE∗
N/A
N/A
NE: norepinephrine; PE: phenylephrine; MDPE: median performance error; MDAPE: median absolute performance error; SBP: systolic blood pressure; HR: heart rate; CO: cardiac output; CI: cardiac index; SV: stroke volume; SVR: systemic vascular resistance; AUC: area under the curve; Values are mean (standard deviation), median [interquartile range], or number (%);∗P <0.05; ns: no statistical significance between groups; N/A: not available.
