Norepinephrine Infusion Research Articles

Effect of prophylactic infusion of norepinephrine on the prevention of hypotension during vertebroplasty: a randomized clinical trial

BackgroundTransient 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.MethodsThe 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.ResultsA 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.ConclusionProphylactic infusion of norepinephrine before bone cement implantation can stabilize hemodynamics and reduce the incidence of hypotension after implantation of bone cement.

Alterations in the Renin-Angiotensin System in Experimental Septic Shock.

To analyze dynamic changes in the renin-angiotensin system (RAS) during septic shock, focusing on angiotensin-converting enzyme (ACE) activity and the balance between angiotensin peptides, using a mass spectrometry method. Experimental septic shock model induced by peritonitis in swine. Experimental Laboratory, Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles. Forty time points from eight mechanically ventilated pigs. Septic shock was induced using intraperitoneal instillation of autologous feces, followed by standardized fluid resuscitation, norepinephrine infusion, antibiotic administration, and peritoneal lavage. The induction of sepsis resulted in a significant increase in plasma renin activity and levels of angiotensin I and II, with a significant decrease in ACE activity observed from 4 hours post-resuscitation and a notable rise in the angiotensin I/angiotensin II ratio at 12 hours. Additionally, a shift toward the angiotensin-(1-7) axis was observed, evidenced by an increased angiotensin-(1-7)/angiotensin II ratio. The study highlighted dynamic shifts in the RAS during septic shock, characterized by reduced circulating ACE activity, elevated angiotensin I/II ratio, and a shift toward the angiotensin-(1-7) axis. These findings suggest an adaptive response within the RAS, potentially offering new insights into sepsis management and therapeutic targets.

Optimal Infusion Rate of Norepinephrine for Prevention of Spinal Hypotension for Cesarean Delivery: A Randomized Controlled Trial, Using Up-Down Sequential Allocation.

Norepinephrine has recently been suggested to be as effective as phenylephrine for the prevention of hypotension after spinal anesthesia for cesarean delivery. Moreover, compared to phenylephrine, norepinephrine may be superior in maintaining heart rate (HR) and consequently, cardiac output (CO). A recent study demonstrated that norepinephrine given as a single intravenous bolus is approximately 13 times more potent than phenylephrine. However, it is uncertain whether this finding can be applied when these vasopressors are administered as infusions. Therefore, the optimum infusion rate of norepinephrine remains unknown. We aimed to determine the median effective dose (ED50; defined as the rate of vasopressor infusion required to prevent spinal hypotension in 50% of subjects) of both drugs needed to maintain maternal systolic blood pressure within 20% of the baseline after spinal anesthesia for cesarean delivery and to derive the relative potency ratio. Sixty healthy patients undergoing elective cesarean delivery with standardized spinal anesthesia were randomized into 2 groups. The first patient in group 1 received phenylephrine 1200 µg in normal saline 0.9% w/v 60 mL at 60 mL/h infusion rate (20 µg.min-1). The first patient in group 2 received norepinephrine 96 µg in normal saline 0.9% w/v 60 mL at 60 mL/h infusion rate (1.6 µg.min-1). Using up-down sequential allocation technique, the vasopressor dose for every subsequent patient was determined by the response in the previous patient. If effective, the next patient received a dose reduced by 150 µg of phenylephrine (2.5 µg.min-1) or 12 µg (0.2 µg.min-1) of norepinephrine. If ineffective, the dose for the next patient was increased by the same amount. The ED50s were determined according to the Dixon-Massey formula. Stroke volume (SV), HR, and CO were also measured. The ED50 was 12.7 µg.min-1 (95% CI, 10.5-14.9) for phenylephrine and 1.01 µg.min-1 (95% CI, 0.84-1.18) for norepinephrine, giving a potency ratio of 12.6 (95% CI, 9.92-15.9). HR, SV, and CO did not differ between the groups. Norepinephrine is more potent than phenylephrine by a factor of approximately 13 when administered as infusion for equivalent maternal blood pressure control. Based on these findings, we recommend a variable rate prophylactic infusion of norepinephrine to be initiated at 1.9 to 3.8 µg.min-1 for the management of hypotension during cesarean delivery under spinal anesthesia.

Effect of low-dose norepinephrine combined with goal-directed fluid therapy on postoperative pulmonary complications in lung surgery: A prospective randomized controlled trial

Study objectivePostoperative pulmonary complications (PPCs), the predominant complications following lung surgery, are closely associated with intraoperative fluid therapy. This study investigates whether continuous low-dose norepinephrine infusion combined with goal-directed fluid therapy (GDFT) reduced the risk of PPCs after lung surgery relative to either GDFT alone or standard fluid treatment. DesignA prospective, randomized controlled trial. SettingThe First Affiliated Hospital of Anhui Medical University, Anhui, China. PatientsThe study included 184 patients undergoing elective thoracoscopic lung resection surgery. InterventionsPatients were randomized into three groups based on different fluid treatment regimens: Group C received standard fluid treatment, Group G received GDFT, and Group N received continuous low-dose norepinephrine infusion combined with GDFT. MeasurementsThe primary outcome was the incidence of PPCs, including respiratory infection, atelectasis, pneumothorax, pleural empyema, respiratory failure, pulmonary embolism and bronchopleural fistula, during the postoperative hospital stay. Secondary outcomes were hemodynamic variables and arterial blood gases. Additional recorded parameters included other postoperative complications such as bleeding, postoperative re-intubation, re-hospitalization within 30 days, and the length of hospital stay. Main resultsGroup N showed a significantly lower PPCs incidence during hospitalization compared to Group C (11.5 % vs 27.9 %; odds ratio, 2.98; 95 % confidence interval, 1.17–8.31; P = 0.023). No significant difference in PPCs was found between Group N and Group G (11.5 % vs 14.5 %; odds ratio, 1.31; 95 % confidence interval, 0.46–3.91; P = 0.616). Additionally, there were no significant differences among the three groups in the components of PPCs. Group N showed higher mean arterial pressure and stroke volume index intraoperatively compared to Group C. ConclusionsContinuous low-dose norepinephrine infusion combined with GDFT reduced PPCs incidence in elective lung surgery patients compared with standard fluid management, but showed no difference compared to GDFT alone. Clinical trial registrationChiCTR2200064081.

The effect of using low dose norepinephrine before hypotensive resuscitation in hemorrhagic shock; a randomized controlled trial

Background &amp; Objectives: Hemorrhagic shock is not a very rare occurrence in big hospitals. It might be encountered in the emergency room (ER) or in the operating rooms (OR). A rapid response and systematic management will save the life of the victim. The objective of this research was to investigate the impact of a low dose of norepinephrine (NE) administered prior to the initiation of hypotensive resuscitation in patients with hemorrhagic shock. Methodology: This randomized controlled trial was conducted on 200 participants, at least 18 years old, classified as severely traumatized and had significant hemorrhage with mean arterial pressure ranging from 65 to 75 mmHg. We divided the patients into two equal groups. Group I received a low dose of NE (&lt; 0.3 µg/kg/min) concurrently with resuscitation fluids. Group II received resuscitative fluids only. If the resuscitative fluids failed to keep mean arterial pressure (MAP) &gt; 65 mmHg, the patient was progressively administered NE even with high doses (0.05 to more than 0.3 µg/kg/min). The primary outcome was 24-hour mortality. In-hospital mortality, incidence of acute kidney injury (AKI), and duration of hospital and intensive care unit (ICU) stay constituted the secondary outcomes. Results: Group I had lower 24-hour mortality compared to Group II (3% vs 13%; P &lt; 0.05). Compared to Group II, Group I needed reduced amount of fluid resuscitation within 24 h, had lower serum lactate levels at 6 and 12 h, and lower serum creatinine at 6, 12, and 18 h (P &lt; 0.001). Group I had a lower incidence of mechanical ventilation (13% vs 27%), hospital and ICU stays, and in-hospital mortality (9% vs 21%) (P &lt; 0.05). There was a lack of disparity seen in the incidence of AKI and duration of mechanical ventilation. Conclusion: Low-dose norepinephrine infusion during the early period of hypotensive resuscitation reduces resuscitative fluid requirement, improves tissue perfusion, preserves renal function, and lowers mortality in hemorrhagic shock patients. Abbreviations: AKI - acute kidney injury; APACHE III - Acute Physiology And Chronic Health Evaluation III; HS - hemorrhagic shock; ICU - intensive care unit; MAP - mean arterial pressure; NE - Norepinephrine Keywords: Hemorrhagic Shock; Hypotensive Resuscitation; Norepinephrine; Fluid Therapy; Renal Protection; Mortality; Low Dose Citation: Mohamed RM, Anwar AG, Eid AA. The effect of using low dose norepinephrine before hypotensive resuscitation in hemorrhagic shock; a randomized controlled trial. Anaesth. pain intensive care 2024;28(5):914−921; DOI: 10.35975/apic.v28i5.2560 Received: April 17, 2024; Reviewed: August 03, 2024; Accepted: September 04, 2024

The Effects of Angiotensin II versus Norepinephrine on Pulmonary Vascular Resistance in Cardiac Surgery: Post Hoc Analysis of a Randomized Controlled Trial

ObjectivesTo assess whether angiotensin II infusion increases pulmonary vascular resistance (PVR) relative to norepinephrine. DesignSecondary analysis of a double-blinded randomized feasibility study. SettingTwo tertiary metropolitan hospitals in Melbourne, Australia. ParticipantsAdult patients having cardiac surgery using cardiopulmonary bypass with an elevated risk of acute kidney injury (AKI). InterventionsAngiotensin II infusion compared with norepinephrine infusion. Measurements and main resultsWe studied 58 patients. There was no significant difference in the primary outcome of PVR both intraoperatively and postoperatively between the angiotensin II and norepinephrine groups. The study drug (angiotensin II or norepinephrine) infusion rate was associated with a small increase in PVR (Β=0.08, p=0.01). The strongest association with PVR was the random effect (patient effect) (p<0.001), This effect was consistent across secondary outcomes. Randomization to norepinephrine (but not angiotensin II) was associated with reduced mean systemic arterial to mean pulmonary arterial pressure ratio postoperatively (Β=-0.65, p=0.01). ConclusionsThe results of this study suggest that, in cardiac surgery patients and compared with norepinephrine, at doses used in the prior feasibility study, angiotensin II did not have significant effects on the pulmonary vasculature. Moreover, at doses used in this study, neither drug appeared to have a substantial effect on the pulmonary circulation relative to surgical and patient factors.

Comparison of mephentermine and norepinephrine infusions for prevention of post-spinal hypotension during elective caesarean delivery: a randomised, double-blind trial

Comparison of mephentermine and norepinephrine infusions for prevention of post-spinal hypotension during elective caesarean delivery: a randomised, double-blind trial

The efficacy and safety of remimazolam tosilate compared with propofol for endoscopic retrograde cholangiopancreatography under monitored anesthesia care: A single-center randomized controlled clinical trial

BackgroundAlthough remimazolam tosilate is an ultra-short-acting benzodiazepine that causes less respiratory and circulatory depression than propofol, studies evaluating its efficacy and safety during endoscopic retrograde cholangiopancreatography (ERCP) are limited. This study aimed to compare the efficacy and safety of remimazolam and propofol for ERCP performed under monitored anesthesia care (MAC). MethodsThis study is a randomized controlled clinical trial featuring a noninferiority design. A total of 102 eligible patients undergoing ERCP under MAC were randomly assigned to either the remimazolam tosilate group (R group) or the propofol group (P group) in a 1:1 ratio. Patients in the R group were sedated with remimazolam tosilate, while those in the P group received propofol, both under MAC. The primary efficacy endpoint was the success rate of ERCP completion under MAC. Secondary outcomes included the time to loss of consciousness, sedative effects, and perioperative adverse events at various time points for patients in both groups. ResultsBaseline characteristics of both groups were similar. The successful completion rate for ERCP under MAC was 100 % in the R group and 96.1 % in the P group, resulting in a difference of 3.92 % (95 % CI: −2%, 10 %). This difference met the pre-established criterion of being greater than −8%. The total number of norepinephrine infusions, as well as the incidence of intravenous injection pain, post-induction hypotension, post-induction bradycardia, intraoperative hypotension, respiratory depression, and hypoxemia, were significantly lower in the R group compared to the P group. Conversely, the total number of phloroglucinol uses, body movements, and instances of rapid gastrointestinal peristalsis were significantly higher in the R group than in the P group. DiscussionRemimazolam-based MAC for ERCP exhibited non-inferior efficacy compared to propofol-based MAC, while also resulting in fewer circulatory and respiratory adverse events during the procedures. Nevertheless, future studies with larger sample sizes are required to evaluate the utility of remimazolam in elderly patients.

Mean arterial pressure versus cardiac index for haemodynamic management and myocardial injury after hepatopancreatic surgery: A randomised controlled trial.

Myocardial injury after noncardiac surgery (MINS) frequently complicates the peri-operative period and is associated with increased mortality. We hypothesised that cardiac index (CI) based haemodynamic management reduces peri-operative high-sensitive troponin-T (hsTnT) elevation and MINS incidence in patients undergoing hepatic/pancreatic surgery compared to mean arterial pressure. A randomised controlled study. A single-centre study conducted in a university-affiliated tertiary hospital between June 2022 and March 2023. Ninety-one patients, who were ≥ 65 years old or ≥ 45 years old with a history of at least one cardiac risk factor were randomised to either mean arterial pressure (MAP) based (n = 45) or CI-based (n = 46) management groups, and completed the study. In group-MAP, patients received fluid boluses and/or a noradrenaline infusion to maintain MAP above the predefined threshold. In group-CI, patients received fluid boluses and/or dobutamine infusion to keep CI above the predefined threshold. When a low MAP was observed despite a normal CI, a noradrenaline infusion was started. The primary outcome was peri-operative hsTnT elevation. The secondary outcomes were MINS incidence and 90-day mortality. The median absolute troponin elevation was 4.3 ng l-1 (95% CI 3.4 to 6) for the CI-based group, and 9.4 ng l-1 (95% CI 7.7 to 12.7) for the MAP-based group (median difference: 5.1 ng l-1, 95% CI 3 to 7; P < 0.001). MINS occurred in 8 (17.4%) patients in the CI-based group and 17 (37.8%) patients in the MAP-based group (relative risk: 0.46, 95% CI: 0.22 to 0.96; P = 0.029). Two patients in group-MAP died from cardiovascular-related causes. One patient in group-CI and two in group-MAP died from sepsis-related complications (for all-cause mortality: χ2 = 1.98, P = 0.16). MAP-AUC and CI-AUC values of the CI- and MAP-based groups were 147 vs. 179 min × mmHg (P = 0.85) and 8.4 vs. 43.2 l m-2 min-1 × min (P < 0.001), respectively. CI-based haemodynamic management assures sufficient flow and consequently is associated with peri-operative hsTnT elevation and the incidence of MINS compared to MAP. Clinicaltrials.gov identifier: NCT05391087.

Transpulmonary cardiac output with room temperature saline is accurate and tracks directional changes in anesthetized dogs.

To assess the performance of transpulmonary thermodilution (TPTD) using room-temperature saline (CORT) and waveform-derived continuous CO (CCO) compared with TPTD using iced saline (COICED) as the indicator for measurements of CO in isoflurane-anesthetized dogs. 8 Beagles aged 1 to 2 years (7.4 to 11.2 kg) were enrolled in this experimental study from March 21 to 31, 2023. Dogs were anesthetized with 0.01 mg/kg acepromazine, 5 to 6 mg/kg propofol, and isoflurane and were mechanically ventilated. Dogs were instrumented with a central venous catheter and a femoral arterial catheter equipped with a thermistor. The COICED, CORT, and pulse wave-derived CCO values were obtained at baseline, during infusions of phenylephrine and norepinephrine, and during blood withdrawal and replacement. Data were analyzed with a mixed effect model, Bland-Altman plots, and concordance. Percent error was calculated. P < .05 was used for significance. Data were collected from 8 dogs. Significant effects of time and the interaction of time and method were found. Bland-Altman plots showed negligible bias with limits of agreement between -0.35 and 0.25 L/min for CORT versus COICED and -1.23 and 1.15 L/min for CCO versus COICED. Percent errors were 17.7% and 66.6%, respectively. In the 4-quadrant plots, the concordance rate was 95% and 68% for measurements obtained with CORT and for CCO, respectively. Transpulmonary thermodilution using room temperature saline was accurate and able to track changes in CO. Continuous CO had a large percent error and low tracking ability. Transpulmonary thermodilution using room temperature saline is reliable for monitoring CO and obviates the need for iced preparations in clinical scenarios.

Veno-Venous Extracorporeal Membrane Oxygenation in COVID-19-Associated ARDS: Predictors of Mortality

The aim of the study was to identify factors associated with hospital mortality in patients with COVID-19associated acute respiratory distress syndrome (ARDS) receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO).Materials and methods. The retrospective study included data from the medical records of 123 patients treated in the intensive care unit (ICU) № 7 of the City Clinical Hospital № 52 of Moscow Department of Health. ECMO was initiated in all patients for respiratory indications according to current recommendations. A number of factors potentially associated with mortality were systematized and analyzed. Statistical processing to identify predictors of death included univariate analysis and calculation of odds ratio (OR), ROC analysis with calculation of area under the ROC curve (AUROC).Results. The resulting mortality rate was 87% (107/123), 11% (14/107) of all deaths occurred after weaning from ECMO. High VV-ECMO flow, delayed initiation of mechanical ventilation and ECMO therapy, and low pH at the time of ECMO initiation were identified as independent predictors of death in the study group. Low median albumin concentration and prolonged use of vasopressors were identified as predictors of death within 28 days of initiation of VV-ECMO. Development of acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), septic shock and its recurrences, and the use of extracorporeal blood purification therapy for septic shock were found to be predictors of death during VV-ECMO therapy.Conclusion. High-flow VV-ECMO regimen, delayed initiation of mechanical ventilation and ECMO support, hypoalbuminemia, prolonged need for norepinephrine infusion, development of AKI requiring CRRT, septic shock occurrence and the number of its recurrences requiring extracorporeal blood purification therapy during VV-ECMO support were identified as predictors of death in patients with COVID-19-associated ARDS after initiation of VV-ECMO therapy.

Development of modified laser Doppler flowmetry device for real-time monitoring of esophageal mucosal blood flow: a preclinical assessment with an animal model.

This study aimed to modify a laser Doppler flowmeter designed and assembled at our institute. After measuring sensitivity evaluation in ex vivo experiments, we confirmed the efficacy of this new device for monitoring real-time esophageal mucosal blood flow changes after thoracic stent graft implantation by simulating various clinical situations in an animal model. Thoracic stent graft implantation was performed in a swine model (n = 8). Esophageal mucosal blood flow decreased significantly from baseline (34.1 ± 18.8ml/min/100g vs. 16.7 ± 6.6ml/min/100g, P < 0.05) in the lower esophagus (Th6-Th8) where the stent graft covered the aorta. In the hemorrhagic shock model (shock index ≥ 1.0), esophageal mucosal blood flow showed a remarkable change from baseline in the upper esophagus (Th1-Th3), where the stent graft did not cover the aorta (20.8 ± 9.8ml/min/100g vs. 12.9 ± 8.6ml/min/100g, P < 0.01); however, it returned to the baseline value within a 30-min period. Mucosal blood flow remained stable in the esophagus, where the stent graft did not cover the aorta. After elevating the mean blood pressure to > 70mmHg with continuous intravenous noradrenaline infusion, esophageal mucosal blood flow increased significantly in both regions; however, the reaction was different between the two regions. Our newly developed laser Doppler flowmeter could measure real-time esophageal mucosal blood flow changes in various clinical situations during thoracic stent graft implantation in a swine model. Hence, this device can be applied in many medical fields by downsizing it.

CRITICAL NOREPINEPHRINE DOSE TO PREDICT EARLY MORTALITY DURING CIRCULATORY SHOCK IN INTENSIVE CARE: A RETROSPECTIVE STUDY IN 3423 ICU PATIENTS OVER 4-YEAR PERIOD.

Introduction: The maximal norepinephrine (NE) dose >1 μg/kg/min during circulatory shock apparently is associated with higher mortality, but this threshold needs confirmation. This study aimed at investigating whether NE infusion at a dose >1 μg/kg/min could predict early intensive care unit (ICU) mortality (first 5 days). The secondary objective was to assess the day-by-day relationship between NE dose during the first 4 days of ICU stay and subsequent mortality. Methods: We conducted a retrospective analysis of data from ICU patients receiving NE for circulatory shock at the Nimes University Hospital (France) from January 2016 to December 2019. Results: A total of 5,735 patients were admitted, 3,693 were screened, and 3,423 were analyzed. NE infusion at a dose >1 μg/kg/min was associated with day-5 mortality (hazards ratio: 7.40, P < 0.0001). The area under the receiver operating characteristic was 0.79 to predict day-5 mortality in ICU for maximal NE >1 μg/kg/min. The calculated threshold of 1.13 μg/kg/min for maximal NE was the best prognostic value (sensitivity: 67%, specificity: 80%, positive predictive value: 45%). When the 1.2 μg/kg/min threshold was crossed either on the first, second, third, or fourth day of ICU stay, the probability of subsequent death was 47%, 49%, 60%, and 40%, respectively. Along the first 4 days of ICU stay, the risk of death increased with increasing NE infusion dose. Conclusions: An NE infusion rate >1.13 μg/kg/min predicts day-5 mortality in ICU patients with circulatory shock. The time to reach maximal NE infusion rate was shorter in survivors than in nonsurvivors.

Linear Correlation Between Mean Arterial Pressure and Urine Output in Critically Ill Patients.

Mean arterial pressure (MAP) plays a significant role in regulating tissue perfusion and urine output (UO). The optimal MAP target in critically ill patients remains a subject of debate. We aimed to explore the relationship between MAP and UO. A retrospective observational study. A general ICU in a tertiary medical center. All critically ill patients admitted to the ICU for more than 10 hours. None. MAP values and hourly UO were collected in 5,207 patients. MAP levels were categorized into 10 groups of 5 mm Hg (from MAP < 60 mm Hg to MAP > 100 mg Hg), and 656,423 coupled hourly mean MAP and UO measurements were analyzed. Additionally, we compared the UO of individual patients in each MAP group with or without norepinephrine (NE) support or diuretics, as well as in patients with acute kidney injury (AKI).Hourly UO rose incrementally between MAP values of 65-100 mm Hg. Among 2,226 patients treated with NE infusion, mean UO was significantly lower in the MAP less than 60 mm Hg group (53.4 mL/hr; 95% CI, 49.3-57.5) compared with all other groups (p < 0.001), but no differences were found between groups of 75 less than or equal to MAP. Among 2500 patients with AKI, there was a linear increase in average UO from the MAP less than 60 mm Hg group (57.1 mL/hr; 95% CI, 54.2-60.0) to the group with MAP greater than or equal to 100 mm Hg (89.4 mL/hr; 95% CI, 85.7-93.1). When MAP was greater than or equal to 65 mm Hg, we observed a statistically significant trend of increased UO in periods without NE infusion. Our analysis revealed a linear correlation between MAP and UO within the range of 65-100 mm Hg, also observed in the subgroup of patients treated with NE or diuretics and in those with AKI. These findings highlight the importance of tissue perfusion to the maintenance of diuresis and achieving adequate fluid balance in critically ill patients.

Experiencia en DAC cardiaca en la Comunidad Valenciana: programa de extracción cardiaca extrahospitalaria

IntroductionIn Spain, since 2020, hearts obtained from donation after circulatory determination of death (DCD) have been used for heart transplants. We show our experience from the beginning of the heart DCDs program. An out-of-hospital cardiac extraction protocol has been implemented within the Valencian Community. Materials and methodFrom November 2022 to April 2024, 21 cardiac assessments have been performed in the context of DCD.Donor inclusion criteria: donor <55years old; family donation consent; functional warm ischemia time <30min.Donor exclusion criteria, additional to those of a cardiac donation: adrenaline infusion; dobutamine infusion; norepinephrine infusion >0,3μg/kg/min.This is a retrospective descriptive study. ResultsOf the 21 possible donors, 19 were valid hearts, 2 of them were for a hospital outside the community. The mean age of the donors was 40.4years, most of them men. In total, 17 patients were transplanted in our hospital. The mean cardiac ischemia time was 136.41min. Primary graft failure was described in 8 patients. ConclusionsThe cardiopulmonary bypass allowed continuous monitoring of aerobic and anaerobic metabolism, correct emptying of the cardiac chambers and the administration of cardioplegia with pressure, temperature and flow control.Our experience highlights the possibilities of success with hearts obtained from a DCD, representing an increase in the number of donors and a decrease in the waiting time for the transplant.

Norepinephrine mediates heart block during severe hypoglycemia in male rats.

Hypoglycemia is common in people with type 1 diabetes. Sometimes, severe hypoglycemia can be fatal. The underlying mechanisms by which severe hypoglycemia can lead to death are unclear. The sympathetic nervous system is thought to be proarrhythmic. We hypothesized that norepinephrine is the main mediator of severe hypoglycemia-induced fatal cardiac arrhythmias. To test this hypothesis, adult, non-diabetic Sprague-Dawley rats were subjected to hyperinsulinemic-severe hypoglycemic clamps (3 h, 10-15 mg/dL) during two different experiments: (1) intracerebroventricular (ICV) norepinephrine (n = 26) or artificial cerebrospinal fluid (aCSF) (n = 20) infusion or (2) blockade of norepinephrine release by intraperitoneal reserpine (n = 20) or control (n = 29). In experiment 1, brain norepinephrine infusion during severe hypoglycemia led to a 2.5-fold increase in third-degree heart block and a 24% incidence of ST elevation compared to no ST elevation in aCSF controls. In experiment 2, reserpine successfully reduced plasma and cardiac norepinephrine levels. During severe hypoglycemia, reserpine completely prevented second and third-degree heart block and T wave increases, a marker of myocardial infarction, compared to controls. In conclusion, norepinephrine increases while reserpine, used to reduce norepinephrine nerve terminal release, reduces heart block and markers of myocardial infarction during severe hypoglycemia.

Intravenous initial bolus during prophylactic norepinephrine infusion to prevent spinal hypotension for cesarean delivery: A randomized controlled, dose-finding trial

BackgroundPrevious 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. MethodsThis 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. ResultsThe 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. ConclusionsAn 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.

Norepinephrine versus phenylephrine affects prethrombotic response in patients undergoing cesarean section under spinal anesthesia: a randomized, double-blind, controlled study.

Venous thromboembolism (VTE) is one of the most common and serious complications of cesarean section in parturients. Norepinephrine (NE) has been shown to activate coagulation. The aim of this study was to compare the effect of a fixed-rate prophylactic norepinephrine infusion and a fixed-rate prophylactic phenylephrine（PHE） infusion under spinal anesthesia for caesarean section on the prethrombotic response. Sixty-six women undergoing cesarean section under spinal anesthesia were randomly assigned to the NE group or PHE group, starting simultaneously with the administration of the subarachnoid solution, a "study drug" solution containing either NE or PHE was pumped intravenously at a constant rate of 15 ml/h until the end of the operation. Plasma coagulation factor VIII activity (FVIII: C), Fibrinogen, and D-dimer levels were measured in blood samples obtained on admission to the operating theatre and at the end of the procedure. Compared with preoperative levels, there were no significant differences in postoperative fibrinogen and D-dimer levels in the NE group, except for a decrease in FVIII: C levels (P = 0.003). However, postoperative levels of FVIII: C (P = 0.009), fibrinogen (P = 0.035) and D-dimer (P = 0.025) were increased in the NE group compared with postoperative levels in the PHE group. NE does not affect the maternal prethrombotic response and can be safely used in cesarean sections. Compared with PHE infusion, NE infusion increased the level of coagulation molecules, suggesting that NE maybe more beneficial for women with high intraoperative bleeding requiring hemostasis.

ULTRASOUND-GUIDED ANTERIOR SCIATIC NERVE BLOCK AND FEMORAL NERVE BLOCK FOR MANAGEMENT OF ABOVE KNEE AMPUTATION IN A POSTOPERATIVE TIBIA EXTERNAL FIXATION PATIENT WITH SEPTIC SHOCK: A CASE REPORT

This case report describes the successful management of a 50-year-old male patient with septic shock following a right tibia external fixation surgery, who was subsequently scheduled for an above knee amputation. The patient presented with hypoxia, hypotension, and required intubation in intensive care unit. In addition, the patient was placed on a noradrenaline infusion due to persistent hypotension. Laboratory investigations revealed thrombocytopenia, elevated procalcitonin levels, increased C-reactive protein, elevated myoglobin levels, and elevated D-dimer levels. Given the patients critical condition, an ultrasound-guided anterior sciatic nerve block and femoral nerve block were performed for surgery. This case report discusses the successful perioperative management of the patients septic shock and the potential role of regional nerve blocks in such critically ill patients.

Impact of Norepinephrine and Dopamine Infusion on Renal Arterial Resistive Index during Pre-Emptive Living Donor Kidney Transplantation: Propensity Score Matching Analysis.

Background: Living donor kidney transplantation (LDKT) is a crucial treatment for end-stage renal disease, with pre-emptive LDKT (transplantation before dialysis initiation) offering significant benefits in graft function and patient survival. The selection of a vasopressor during LDKT, particularly between norepinephrine and dopamine, and its impact on renal arterial hemodynamics measured using the renal arterial resistive index (RARI) is poorly understood. Methods: This retrospective observational cohort study enrolled 347 eligible pre-emptive LDKT recipients from the Seoul St. Mary's Hospital between January 2019 and June 2023. Utilizing propensity score matching (PSM), the patients were categorized into dopamine and norepinephrine groups to compare the effects of these vasopressors on the intraoperative RARI, postoperative estimated glomerular filtration rate (eGFR), and hourly urine output. The RARI was measured via the Doppler ultrasonography of the renal hilum and parenchyma post-graft vascular and ureteral anastomoses. Results: The preoperative differences in the recipients' and donors' characteristics were mitigated following PSM. The dopamine group exhibited higher intraoperative RARI values at the renal hilum (0.77 ± 0.11 vs. 0.66 ± 0.13, p < 0.001) and parenchyma (0.71 ± 0.1 vs. 0.6 ± 0.1, p < 0.001) compared to those of the norepinephrine group. However, these differences were not statistically significant on postoperative day 7. The norepinephrine infusion adjusted for the propensity scores was associated with significantly lower odds of an RARI > 0.8 (hilum: OR = 0.214, 95% CI = 0.12-0.382, p < 0.001; parenchyma: OR = 0.1, 95% CI = 0.029-0.348, p < 0.001). The early postoperative outcomes showed a higher eGFR (day 1: 30.0 ± 13.3 vs. 25.1 ± 17.4 mL/min/1.73 m2, p = 0.004) and hourly urine output (day 1: 41.8 ± 16.9 vs. 36.5 ± 14.4 mL/kg/h, p = 0.002) in the norepinephrine group. Furthermore, the long-term outcomes were comparable between the groups. Conclusions: Norepinephrine infusion during pre-emptive LDKT is associated with more favorable intraoperative renal arterial hemodynamics, as evidenced by a lower RARI and improved early postoperative renal function compared to those of dopamine. These findings suggest a potential preferential role for norepinephrine in optimizing perioperative management and early graft functions in LDKT recipients. Given the retrospective nature of this study, further prospective studies are needed to confirm these observations. Additionally, the study limitations include the potential for unmeasured confounding factors and the inability to determine causality due to its observational design.