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In this comparative-effectiveness trial, there was no significant difference in the overall survival rate between patients with shock who were treated with dopamine and those who were treated with norepinephrine. However, dopamine was associated with more cardiac arrhythmias and with a higher mortality rate among patients with cardiogenic shock. This comparative-effectiveness trial found no significant difference in overall survival in patients with shock treated with dopamine or with norepinephrine. However, dopamine was associated with more cardiac arrhythmias and a higher mortality rate in those with cardiogenic shock. Circulatory shock is a life-threatening condition that is associated with high mortality. 1 , 2 The administration of fluids, which is the first-line therapeutic strategy, is often insufficient to stabilize the patient's condition, and adrenergic agents are frequently required to correct hypotension. Among these agents, dopamine and norepinephrine are used most frequently. 3 Both of these agents influence alpha-adrenergic and beta-adrenergic receptors, but to different degrees. Alpha-adrenergic effects increase vascular tone but may decrease cardiac output and regional blood flow, especially in cutaneous, splanchnic, and renal beds. Beta-adrenergic effects help to maintain blood flow through inotropic and chronotropic effects and to increase splanchnic . . .

In a multicenter trial, 778 patients with septic shock who were being treated with catecholamine vasopressors were randomly assigned to either norepinephrine or vasopressin in addition to open-label vasopressors. There was no significant difference between the two groups in mortality at either 28 or 90 days, nor was there any significant difference in the rate of adverse events. Patients with septic shock were randomly assigned to either norepinephrine or vasopressin in addition to open-label vasopressors. There was no significant difference between the two groups in mortality at either 28 or 90 days. Septic shock is the most common cause of death in intensive care units (ICUs) 1 , 2 and has a mortality rate of 40 to 60%. 2 , 3 Resuscitation strategies include the administration of intravenous fluids and the use of catecholamines such as norepinephrine, epinephrine, dopamine, and dobutamine. 4 , 5 Although largely effective in reestablishing minimally acceptable mean arterial pressures to maintain organ perfusion, catecholamines have important adverse effects and may even increase mortality rates. 6 For example, norepinephrine, a potent and commonly used α-adrenergic agent in cases of septic shock, may decrease cardiac output, oxygen delivery, and blood flow to vulnerable organs despite adequate . . .

International guidelines for management of septic shock recommend that dopamine or norepinephrine are preferable to epinephrine. However, no large comparative trial has yet been done. We aimed to compare the efficacy and safety of norepinephrine plus dobutamine (whenever needed) with those of epinephrine alone in septic shock. This prospective, multicentre, randomised, double-blind study was done in 330 patients with septic shock admitted to one of 19 participating intensive care units in France. Participants were assigned to receive epinephrine (n=161) or norepinephrine plus dobutamine (n=169), which were titrated to maintain mean blood pressure at 70 mm Hg or more. The primary outcome was 28-day all-cause mortality. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00148278. There were no patients lost to follow-up; one patient withdrew consent after 3 days. At day 28, there were 64 (40%) deaths in the epinephrine group and 58 (34%) deaths in the norepinephrine plus dobutamine group (p=0·31; relative risk 0·86, 95% CI 0·65–1·14). There was no significant difference between the two groups in mortality rates at discharge from intensive care (75 [47%] deaths vs 75 [44%] deaths, p=0·69), at hospital discharge (84 [52%] vs 82 [49%], p=0·51), and by day 90 (84 [52%] vs 85 [50%], p=0·73), time to haemodynamic success (log-rank p=0·67), time to vasopressor withdrawal (log-rank p=0·09), and time course of SOFA score. Rates of serious adverse events were also similar. There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.

Spinal anesthesia often causes hypotension, with consequent risk to the fetus. The use of vasopressor agents has been highly recommended for the prevention of spinal anesthesia-induced hypotension during caesarean delivery. Many studies have shown that norepinephrine can provide more stable maternal hemodynamics than phenylephrine. We therefore tested the hypothesis that norepinephrine preserves fetal circulation better than phenylephrine when used to treat maternal hypotension consequent to spinal anesthesia. Prospective, randomized, double-blinded study. Operating room. We recruited 223 parturients with uncomplicated singleton pregnancies who were scheduled for elective caesarean section under combined spinal-epidural anesthesia. The patients received prophylactic intravenous infusion of either 0.08 μg/kg/min norepinephrine or 0.5 μg/kg/min phenylephrine for prevention of spinal anesthesia-induced hypotension. Changes in fetal heart rate and fetal cardiac output before and after spinal anesthesia were measured using noninvasive Doppler ultrasound. 90 subjects who received norepinephrine infusion and 93 subjects who received phenylephrine infusion were ultimately analyzed in the present study. The effects of norepinephrine and phenylephrine on the change of fetal heart rate and fetal cardiac output at 3 and 6 min after spinal block were similar. Although there was a statistically significant decrease in fetal cardiac output at 6 min after subarachnoid block initiation in both the norepinephrine group (mean difference 0.02 L/min; 95% CI, 0–0.04 L/min; P = 0.03) and the phenylephrine group (mean difference 0.02 L/min; 95% CI, 0–0.04 L/min; P = 0.02), it remained within the normal range. Prophylactic infusion of comparable doses of phenylephrine or norepinephrine has similar effects on fetal heart rate and cardiac output changes after spinal anesthesia. Neither phenylephrine nor norepinephrine has meaningful detrimental effects on fetal circulation or neonatal outcomes. •Prophylactic infusion of comparable doses of phenylephrine or norepinephrine has similar effects on fetal heart rate and cardiac output changes after spinal anesthesia.•Neither phenylephrine nor norepinephrine has meaningful detrimental effects on fetal circulation.

In recent years, norepinephrine has attracted increasing attention for the management of maternal hypotension during elective cesarean section with spinal anesthesia. Intermittent bolus is a widely used administration paradigm for vasopressors in obstetric anesthesia in China. Thus, in this randomized, double-blinded study, we compared the efficacy and safety of equivalent bolus norepinephrine and phenylephrine for rescuing maternal post-spinal hypotension. In a tertiary women's hospital in Nanjing, China, 102 women were allocated with computer derived randomized number to receive prophylactic 8 μg norepinephrine (group N; n = 52) or 100 μg phenylephrine (group P; n = 50) immediately post-spinal anesthesia, followed by an extra bolus of the same dosage until delivery whenever maternal systolic blood pressure became lower than 80% of the baseline. Our primary outcome was standardized maternal cardiac output (CO) reading from spinal anesthesia until delivery analyzed by a two-step method. Other hemodynamic parameters related to vasopressor efficacy and safety were considered as secondary outcomes. Maternal side effects and neonatal outcomes were collected as well. Compared to group P, women in group N had a higher CO (standardized CO 5.8 ± 0.9 vs. 5.3 ± 1.0 L/min, t = 2.37, P = 0.02) and stroke volume (SV, standardized SV 73.6 ± 17.2 vs. 60.0 ± 13.3 mL, t = 4.52, P < 0.001), and a lower total peripheral resistance (875 ± 174 vs. 996 ± 182 dyne·s/cm, t = 3.44, P < 0.001). Furthermore, the incidence of bradycardia was lower in group N than in group P (2% vs. 14%, P = 0.023), along with an overall higher standardized heart rate (78.8 ± 11.6 vs. 75.0 ± 7.3 beats/min, P = 0.049). Other hemodynamics, as well as maternal side effects and neonatal outcomes, were similar in two groups (P > 0.05). Compared to equivalent phenylephrine, intermittent bolus norepinephrine provides a greater CO for management of maternal hypotension during elective cesarean section with spinal anesthesia; however, no obvious maternal or neonatal clinical advantages were observed for norepinephrine.

Previous studies have shown that a 0.05 μg/kg/min of norepinephrine infusion in combination with an initial bolus reduces the incidence of spinal hypotension during cesarean delivery. The initial norepinephrine bolus influences the incidence of spinal hypotension during continuous norepinephrine infusion; however, the ideal initial bolus dose for 0.05 μg/kg/min of continuous infusion remains unknown. This randomized, controlled, dose-finding study randomly allocated 120 parturients scheduled for elective cesarean delivery to receive initial bolus doses of 0, 0.05, 0.10, and 0.15 μg/kg of norepinephrine, followed by continuous infusion at a rate of 0.05 μg/kg/min. The primary outcome was the dose-response relationship of the initial norepinephrine bolus in preventing the incidence of spinal hypotension. Spinal hypotension was defined as systolic blood pressure (SBP) decreased to <80% of the baseline value or to an absolute value of <90 mmHg from intrathecal injection to delivery, and severe spinal hypotension was defined as SBP decreased to <60% of the baseline value. The secondary outcomes included the incidence of nausea and/or vomiting, hypertension, and bradycardia, as well as the Apgar scores and results of the umbilical arterial blood gas analysis. The effective dose (ED) 90 and ED95 were estimated using probit regression. The per-protocol analysis included 117 patients. The incidence of spinal hypotension varied significantly among the groups: Group 0 (51.7%), Group 0.05 (44.8%), Group 0.10 (23.3%), and Group 0.15 (6.9%). The ED90 and ED95 values were 0.150 μg/kg (95% confidence interval [CI], 0.114–0.241 μg/kg) and 0.187 μg/kg (95% CI, 0.141–0.313 μg/kg), respectively. However, the ED95 value fell outside the dose range examined in this study. The incidence of severe spinal hypotension differed significantly (P = 0.02) among Groups 0 (17.2%), 0.05 (10.3%), 0.10 (3.3%), and 0.15 (0.0%); however, the incidence of hypertension and bradycardia did not. The incidence of nausea and/or vomiting decreased with an increase in the initial bolus dose (P = 0.03). The fetal outcomes were comparable among the groups. An initial bolus of 0.150 μg/kg of norepinephrine may be the optimal dose for preventing spinal hypotension during cesarean delivery with a continuous infusion rate of 0.05 μg/kg/min, and does not significantly increase the incidence of hypertension but substantially reduces the risk of nausea and/or vomiting. •An initial bolus reduces the incidence of spinal hypotension with norepinephrine infusion rate at 0.05 µg/kg/min.•The ideal dose of the initial bolus remains unknown.•In this RCT, the ED90, and ED95 values were 0.150 μg/kg and 0.187 μg/kg for preventing spinal hypotension.•The 0.150 μg/kg of norepinephrine may be optimal dose for preventing spinal hypotension during cesarean delivery.

Background Transient hypotension is a common occurrence during the implantation of bone cement. This placebo-controlled randomized clinical trial study investigated the effect of prophylactic infusion of norepinephrine on the incidence of hypotension in senior patients who underwent vertebroplasty. Methods The trial recruited patients who were greater than or equal to 65 years of age, had an American Society of Anesthesiologist physical status classification of I to III, and underwent vertebroplasty from August 2020 to August 2021 at the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine in China. The patients were randomly grouped according to whether they received either a norepinephrine infusion of 0.05 µg/kg/min or an equivalent volume of saline 10 min before implantation of bone cement. Intraoperative hemodynamics were monitored continuously by the MostCare system at the following 7 time points: 10 min before implantation of bone cement and immediately, 30 s, 1, 3, 5, and 10 min after implantation of bone cement. We also recorded the number of hypotensive episodes and the total number of vasopressors after implantation of bone cement. Multivariable logistic regression was used to assess the risk factors associated with hypotension after implantation of bone cement. Results A total of 63 patients were randomized to the control group ( n  = 31; median [IQR] age, 74 [69–79] years) and the norepinephrine group ( n  = 32; median [IQR] age, 75 [71–79] years). The incidence of hypotension in the norepinephrine group was significantly lower than that in the control group after implantation of bone cement (12.5% vs. 45.2%; relative risk [RR], 3.61 [95% CI, 1.13–15.07]; P  = 0.005). Moreover, the median (IQR) number of hypotensive episodes (0 [0–0] vs. 0 [0–2]; P  = 0.005) and the total number of vasopressors (0 [0–0] vs. 0 [0–1]; P  = 0.004) in the norepinephrine group were significantly lower than those in the control group. Furthermore, compared with the baseline, the MAP significantly decreased at 1 min ( P  = 0.007) and 3 min ( P <  0.001) after bone cement implantation in the control group. However, the MAP at 3 min in the norepinephrine group was significantly higher than that in the control group ( P  < 0.001). The incidence of complications was not different between the groups. In multivariable logistic regression, the FRAIL score (OR, 2.29; 95% CI, 1.21–4.31) was identified as a risk factor associated with hypotension. Conclusion Prophylactic infusion of norepinephrine before bone cement implantation can stabilize hemodynamics and reduce the incidence of hypotension after implantation of bone cement.

[...]the prevention of renal function deterioration in the early postoperative period is important [11,12]. [...]a high dose of norepinephrine, can negatively affect renal function [14,15]. Variables AKI – (n = 265) AKI + (n = 65) p value Bonferroni Baseline characteristics Age (years) 68.0 [61.0–73.0] 67.0 [63.0–74.0] 0.298 1 Male gender (n, %) 198 (74.7) 51 (78) 0.530 1 BMI (kg.m−2) 27.0 [23.9–30.9] 28.9 [25.2–31.2] 0.291 1 Chronic Kidney disease 17 (6.6) 13 (20.0) 0.002 0.040 Diabetes 65 (25.2) 21 (32.3) 0.247 1 Hypertension 150 (58.1) 39 (60.0) 0.786 1 Acute coronary syndrome 54 (20.9) 19 (29.2) 0.155 1 Stroke 19 (7.4) 3 (4.6) 0.436 1 LVEF (%) 60.0 [53.0–66.3] 60.0 [54.5–69.0] 0.753 1 Surgery type (n, %) 0.681 1 Ascending Aorta 3 (1.2) 0 (0.0) – Combined surgery (CABG and valve) 29 (11.4) 10 (15.4) – Isolated CABG 77 (30.2) 14 (21.5) – Valve replacement 7 (2.7) 2 (3.1) – Euroscore II 3.47 [2.0, 7.2] 4.1 [2.7–9.5] 0.071 1 Intraoperative characteristics Duration of CPB (min) 93.0 [68.7–122.0] 104.0 [60.5–141.5] 0.040 1 Duration of aortic clamp (min) 69.0 [50.0–91.0] 66.0 [44.5–96.0] 0.213 1 Scv02 (%) 78.8 [73.4–83.5] 78.7 [74.2–84.9] 0.770 1 CPB blood flow (ml/min) 5025.3 [4476.0–5360.0] 5092.2 [4619.1–5514.3] 0.431 1 Mean arterial pressure (mmHg) 68.6 [62.7–73.0] 65.7 [60.9–73.4] 0.306 1 Intraoperative hemoglobin level (g.dl−1) 9.9 [8.9–10.9] 9.5 [8.5–10.9] 0.599 1 RBC transfusion (n, %) 29 (11.4) 16 (24.6) 0.007 0.140 Norepinephrine infusion Cumulative norepinephrine dose (mg) 0.00 [0.0–0.5] 1.05 [0.0–7.3] <0.005 0.006 Number of patients receiving norepinephrine (n(%)).

Background Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. Methods A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80–85 mmHg (high-target) and 65–70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients’ condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 μg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. Discussion The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. Trial registration UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

BackgroundVasopressors are administered to critically ill patients with vasodilatory shock not responsive to volume resuscitation, and less often in cardiogenic shock, and hypovolemic shock.ObjectivesThe objectives are to review safety and efficacy of vasopressors, pathophysiology, agents that decrease vasopressor dose, predictive biomarkers, β1-blockers, and directions for research.MethodsThe quality of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE).ResultsVasopressors bind adrenergic: α1, α2, β1, β2; vasopressin: AVPR1a, AVPR1B, AVPR2; angiotensin II: AG1, AG2; and dopamine: DA1, DA2 receptors inducing vasoconstriction. Vasopressor choice and dose vary because of patients and physician practice. Adverse effects include excessive vasoconstriction, organ ischemia, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. No randomized controlled trials of vasopressors showed a significant difference in 28-day mortality rate. Norepinephrine is the first-choice vasopressor in vasodilatory shock after adequate volume resuscitation. Some strategies that decrease norepinephrine dose (vasopressin, angiotensin II) have not decreased 28-day mortality while corticosteroids have decreased 28-day mortality significantly in some (two large trials) but not all trials. In norepinephrine-refractory patients, vasopressin or epinephrine may be added. A new vasopressor, angiotensin II, may be useful in profoundly hypotensive patients. Dobutamine may be added because vasopressors may decrease ventricular contractility. Dopamine is recommended only in bradycardic patients. There are potent vasopressors with limited evidence (e.g. methylene blue, metaraminol) and novel vasopressors in development (selepressin).ConclusionsNorepinephrine is first choice followed by vasopressin or epinephrine. Angiotensin II and dopamine have limited indications. In future, predictive biomarkers may guide vasopressor selection and novel vasopressors may emerge.