Administration Of Norepinephrine Research Articles

The Direct Effects of Norepinephrine Administration on Pressure Injuries in Intensive Care Patients: A Retrospective Cohort Study.

To estimate the direct effects of norepinephrine administration on pressure injury (PI) incidence in intensive care patients. This is a secondary and exploratory analysis of a retrospective cohort study of intensive care patients discharged in 2017 to 2018. Observational cases only included patients who received primary PI preventive care during intensive care (N = 479). As a first-choice vasopressor drug, norepinephrine administration was approximated with days of norepinephrine. Linear path models were examined from norepinephrine administration to PI development. The identification of confounding variables and instrumental variables was grounded on directed acyclic graph theory. Direct effects were estimated with instrumental variables to overcome bias from unobserved variables. As models were re-specified with data analysis, the robustness of path identification was improved by requiring graph invariance with sample split. Norepinephrine caused PI development from one stage to another after 4.0 to 6.3 days of administration in this cohort as a total effect (90% CI). The direct effect was estimated to advance the stage of PI at a rate of 0.140 per day of norepinephrine administered (standard error, 0.029; P < .001). The direct effect accounted for about 70% of the total effect on PI development. Estimations with instrumental variables and structural equation modeling showed that norepinephrine administration directly and substantially affected hospital-acquired PI incidence in intensive care patients in this cohort.

UNVEILING THE SIGNIFICANCE OF DYNAMIC ARTERIAL ELASTANCE: AN INSIGHTFUL APPROACH TO ASSESSING ARTERIAL LOAD IN AN ENDOTOXIN SHOCK MODEL.

Background: The aim of this study was to investigate the relationship between dynamic arterial elastance (EaDyn) and the pulsatile and steady components of arterial load in an endotoxin shock model using a two-element Windkessel model and to describe the behavior of EaDyn in this model. Methods : Ten female Yorkshire pigs were administered lipopolysaccharide intravenously to induce endotoxin shock, while three female pigs served as the control group. Measurements of EaDyn (ratio between pulse pressure variation and stroke volume variation), effective arterial elastance, arterial compliance (Cart), and systemic vascular resistance were taken every 30 min in the endotoxin group until shock was induced. In the control group, these variables were measured every 30 min for 3 h. Subsequently, a fluid load was administered to both groups, and measurements were repeated every 30 min. After 1 hour of shock induction, the endotoxin group was divided into two subgroups: one receiving norepinephrine (END-NE) and the other not receiving it (END-F). Results: EaDyn showed an association with Cart, while pulse pressure variation was connected to both pulsatile and steady components, and stroke volume variation was solely associated with steady components. In addition, EaDyn exhibited higher values in the END groups than in the control group when shock was achieved. Furthermore, after the administration of norepinephrine, EaDyn displayed higher values in END-F than in END-NE. Conclusions: The EaDyn variable helps identify changes in the pulsatile component of arterial load, providing valuable guidance for management strategies aimed at improving cardiac performance.

Prehospital pulse pressure and mortality of septic shock patients cared for by a mobile intensive care unit

BackgroundSeptic shock medical treatment relies on a bundle of care including antibiotic therapy and hemodynamic optimisation. Hemodynamic optimisation consists of fluid expansion and norepinephrine administration aiming to optimise cardiac output to reach a mean arterial pressure of 65mmHg. In the prehospital setting, direct cardiac output assessment is difficult because of the lack of invasive and non-invasive devices. This study aims to assess the relationship between 30-day mortality and (i) initial pulse pressure (iPP) as (ii) pulse pressure variation (dPP) during the prehospital stage among patients cared for SS by a prehospital mobile intensive care unit (MICU).MethodsFrom May 09th, 2016 to December 02nd, 2021, septic shock patients requiring MICU intervention were retrospectively analysed. iPP was calculated as the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the first contact between the patient and the MICU team prior to any treatment and, dPP as the difference between the final PP (the difference between SBP and DBP at the end of the prehospital stage) and iPP divided by prehospital duration. To consider cofounders, the propensity score method was used to assess the relationship between (i) iPP < 40mmHg, (ii) positive dPP and 30-day mortality.ResultsAmong the 530 patients analysed, pulmonary, digestive, and urinary infections were suspected among 43%, 25% and 17% patients, respectively. The 30-day overall mortality rate reached 31%. Cox regression analysis showed an association between 30-day mortality and (i) iPP < 40mmHg; aHR of 1.61 [1.03–2.51], and (ii) a positive dPP; aHR of 0.56 [0.36–0.88].ConclusionThe current study reports an association between 30-day mortality rate and iPP < 40mmHg and a positive dPP among septic shock patients cared for by a prehospital MICU. A negative dPP could be helpful to identify septic shock with higher risk of poor outcome despite prehospital hemodynamic optimization.

Peripheral Administration of Norepinephrine: A Prospective Observational Study

Historically, norepinephrine has been administered through a central venous catheter (CVC) because of concerns about the risk of ischemic tissue injury if extravasation from a peripheral IV catheter (PIVC) occurs. Recently, several reports have suggested that peripheral administration of norepinephrine may be safe. Can a protocol for peripheral norepinephrine administration safely reduce the number of days a CVC is in use and frequency of CVC placement? This was a prospective observational cohort study conducted in the medical ICU at a quaternary care academic medical center. A protocol for peripheral norepinephrine administration was developed and implemented in the medical ICU at the study site. The protocol was recommended for use in patients who met prespecified criteria, but was used at the treating clinician's discretion. All adult patients admitted to the medical ICU receiving norepinephrine through a PIVC from February 2019 through June 2021 were included. The primary outcome was the number of days of CVC use that were avoided per patient, and the secondary safety outcomes included the incidence of extravasation events. Six hundred thirty-five patients received peripherally administered norepinephrine. The median number of CVC days avoided per patient was 1 (interquartile range, 0-2days per patient). Of the 603 patients who received norepinephrine peripherally as the first norepinephrine exposure, 311 patients (51.6%) never required CVC insertion. Extravasation of norepinephrine occurred in 35 patients (75.8 events/1,000d of PIVC infusion [95%CI, 52.8-105.4 events/1,000d of PIVC infusion]). Most extravasations caused no or minimal tissue injury. No patient required surgical intervention. This study suggests that implementing a protocol for peripheral administration of norepinephrine safely can avoid 1 CVC day in the average patient, with 51.6%of patients not requiring CVC insertion. No patient experienced significant ischemic tissue injury with the protocol used. These data support performance of a randomized, prospective, multicenter study to characterize the net benefits of peripheral norepinephrine administration compared with norepinephrine administration through a CVC.

The Effect of Fluid Pre-loading on Vital Signs and Hemodynamic Parameters in a Porcine Model of Lipopolysaccharide-Induced Endotoxemia.

Background Animal models of distributive hypotension and resuscitation allow the assessment of hemodynamic monitoring modalities and resuscitation strategies. The fluid-first paradigm for resuscitation is currently being challenged with clinical trials. In this investigation, venous return and perfusion are assessed, and full hemodynamics are characterized, in a porcine model of endotoxemic hypotension with and without fluid pre-loading. Methods Two groups of six pigs had the induction of standardized endotoxemic hypotension("critical hypotension"). Group 1 underwent four 10 cc/kg crystalloid boluses, and Group 2 was not fluid pre-resuscitated. Both groups underwent progressive norepinephrine (NE) up-titration to 0.25 mcg/kg/minute over 30 minutes. Vital signs, central parameters, and laboratory values were obtained at baseline, "critical hypotension,"after each bolus and during NE administration. Results Endotoxemia decreased the systemic vascular resistance (SVR) in Group 1 (1031±106 dyn/s/cm-5 versus738±258 dyn/s/cm-5; P=0.03) and Group 2 (1121±196 dyn/s/cm-5 versus759±342 dyn/s/cm-5; P=0.003). In Group 1, the four fluid boluses decreased heart rate (HR), pulmonary capillary wedge pressure (PCWP), and central venous pressure (CVP) (P<0.05). No changes were observed in blood pressure, cardiac output (CO), or lactate. NE up-titration increased HR in Group 1and decreased CVP in both groups. Higher final CVP (11 {3} versus4 {4} mmHg; P=0.01) and PCWP (5 {1} versus2 {2} mmHg; P=0.005) values were observed in Group 1 relative to Group 2, reflecting increased venous return. Conclusions Porcine endotoxemic hypotension and resuscitation were robustly characterized. In this model, fluid loading improved venous return with NE, though perfusion (CO) was preserved by increased NE-induced chronotropy.

Think out of the box: association of left congenital diaphragmatic hernia and abnormal origin of the right pulmonary artery

BackgroundWe report the occurrence of a severe pulmonary hypertension (PH) in a neonate affected by a left congenital diaphragmatic hernia (CDH). PH in this patient was associated with an abnormal origin of the right pulmonary artery from the right brachiocephalic artery. This malformation, sometimes named hemitruncus arteriosus, has to the best of our knowledge never been reported in association with a CDH.Case presentationA male newborn was hospitalized from birth in the neonatal intensive care unit after prenatal diagnosis of a left CDH. Ultrasound examination at 34 weeks of gestational age evaluated the observed-to-expected lung-to-head ratio at 49%. Birth occurred at 38+ 5 weeks of gestational age. Soon after admission, severe hypoxemia, i.e., preductal pulse oximetry oxygen saturation (SpO2) < 80%, prompted therapeutic escalation including the use of high frequency oscillatory ventilation with fraction of inspired oxygen (FiO2) 100% and inhaled nitric oxide (iNO). Echocardiography assessment revealed signs of severe PH and normal right ventricle function. Despite administration of epoprostenolol, milrinone, norepinephrine, and fluid loadings with albumin and 0.9% saline, hypoxemia remained severe, preductal SpO2 inconsistently greater than or equal to 80-85% and post ductal SpO2 lower on average by 15 points. This clinical status remained unchanged during the first 7 days of life. The infant’s clinical instability was incompatible with surgical intervention, while chest X-ray showed a relatively preserved lung volume, especially on the right side. This prompted an additional echocardiography, aimed at searching an explanation of this unusual evolution and found an abnormal origin of the right pulmonary artery, which was confirmed on computed tomography angiography subsequently. A change in the medical strategy was decided, with the suspension of pulmonary vasodilator treatments, the administration of diuretics, and the decrease in norepinephrine dose to decrease the systemic-to-pulmonary shunt. Progressive improvement in the infant respiratory and hemodynamic status enabled to perform CDH surgical repair 2 weeks after birth.ConclusionsThis case recalls the interest of systematic analysis of all potential causes of PH in a neonate with CDH, a condition frequently associated with various congenital malformations.

Impact of Intraoperative Fluid Balance and Norepinephrine on Postoperative Acute Kidney Injury after Cystectomy and Urinary Diversion over Two Decades: A Retrospective Observational Cohort Study

The use of norepinephrine and the restriction of intraoperative hydration have gained increasing acceptance over the last few decades. Recently, there have been concerns regarding the impact of this approach on renal function. The objective of this study was to examine the influence of norepinephrine, intraoperative fluid administration and their interaction on acute kidney injury (AKI) after cystectomy. In our cohort of 1488 consecutive patients scheduled for cystectomies and urinary diversions, the overall incidence of AKI was 21.6% (95%-CI: 19.6% to 23.8%) and increased by an average of 0.6% (95%—CI: 0.1% to 1.1%, p = 0.025) per year since 2000. The fluid and vasopressor regimes were characterized by an annual decrease in fluid balance (−0.24 mL·kg−1·h−1, 95%—CI: −0.26 to −0.22, p &lt; 0.001) and an annual increase in the amount of norepinephrine of 0.002 µg·kg−1·min−1 (95%—CI: 0.0016 to 0.0024, p &lt; 0.001). The interaction between the fluid balance and norepinephrine levels resulted in a U-shaped association with the risk of AKI; however, the magnitude and shape depended on the reference categories of confounders (age and BMI). We conclude that decreased intraoperative fluid balance combined with increased norepinephrine administration was associated with an increased risk of AKI. However, other potential drivers of the observed increase in AKI incidence need to be further investigated in the future.

Adipocyte NMNAT1 expression is essential for nuclear NAD+ biosynthesis but dispensable for regulating thermogenesis and whole-body energy metabolism

Nicotinamide adenine dinucleotide (NAD+) functions as an essential cofactor regulating a variety of biological processes. The purpose of the present study was to determine the role of nuclear NAD+ biosynthesis, mediated by nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1), in thermogenesis and whole-body energy metabolism. We first evaluated the relationship between NMNAT1 expression and thermogenic activity in brown adipose tissue (BAT), a key organ for non-shivering thermogenesis. We found that reduced BAT NMNAT1expression was associated with inactivation of thermogenic gene program induced by obesity and thermoneutrality. Next, we generated and characterized adiponectin-Cre-driven adipocyte-specific Nmnat1 knockout (ANMT1KO) mice. Loss of NMNAT1 markedly reduced nuclear NAD+ concentration by approximately 70% in BAT. Nonetheless, adipocyte-specific Nmnat1 deletion had no impact on thermogenic (rectal temperature, BAT temperature and whole-body oxygen consumption) responses to β-adrenergic ligand norepinephrine administration and acute cold exposure, adrenergic-mediated lipolytic activity, and metabolic responses to obesogenic high-fat diet feeding. In addition, loss of NMNAT1 did not affect nuclear lysine acetylation or thermogenic gene program in BAT. These results demonstrate that adipocyte NMNAT1 expression is required for maintaining nuclear NAD+ concentration, but not for regulating BAT thermogenesis or whole-body energy homeostasis.

Effect of Peripherally Infused Norepinephrine on Reducing Central Venous Catheter Utilization.

The purpose of this retrospective study was to evaluate the impact of peripherally administered norepinephrine on avoiding central venous catheter insertion while maintaining safety of the infusion. An institutional guideline allows peripheral infusion of norepinephrine via dedicated, 16- to 20-gauge, mid-to-upper arm intravenous (IV) catheters for up to 24 hours. The primary outcome was the need for central venous access in patients initially started on peripherally infused norepinephrine. A total of 124 patients were evaluated (98 initially on peripherally infused norepinephrine vs 26 with central catheter only administration). Thirty-six (37%) of the 98 patients who were started on peripheral norepinephrine avoided the need for central catheter placement, which was associated with $8,900 in direct supply cost avoidance. Eighty (82%) of the 98 patients who started peripherally infused norepinephrine required the vasopressor for ≤12 hours. No extravasation or local complications were observed in any of the 124 patients, regardless of site of infusion. Administration of norepinephrine via a dedicated peripheral IV site appears safe and may lead to a reduction in the need for subsequent central venous access. To achieve timely resuscitation goals, as well as to minimize complications associated with central access, initial peripheral administration should be considered for all patients.

Early neonatal sepsis in COVID-19 era

Introduction. Early-onset neonatal sepsis (EONS) remains the leading cause of serious mobility and mortality worldwide. At the present time, the impact of the COVID-19 pandemic on the incidence of other infections is of particular interest. Aim: to conduct a comparative analysis of the features of the course of EONS in newborns before the COVID-19 pandemic (2018) and during the COVID-19 pandemic (2021). Materials and Мethods. A retrospective cohort single-center continuous study included 73 newborns born and hospitalized in the Regional Kaluga Perinatal Center (PC) based on Kaluga Regional Clinical Hospital. The data for the period of stay in the PC from January to October 2018 and the same period in 2021 were analyzed and compared. Newborns were divided into two groups: group 1 (n = 26) – in 2018, and group 2 (n = 47) – in 2021. The following parameters of EONS severity were selected: the need for the use of norepinephrine, surfactant and fresh-frozen plasma (FFP). Results. The incidence of EONS in 2021 (n = 47) was significantly higher than in 2018 (n = 26): odds ratio (OR) = 3.27; 95 % confidence interval (CI) = 1.57–6.40; p = 0,001. Gestational age and Apgar score at the 1st and 5th minutes were significantly higher in group 1 than in group 2: 36.2 [33.3; 38.0] weeks vs. 33.3 [28.5; 36.1] weeks (p = 0.016); 7.0 [5.0; 7.0] vs. 5.0 [3.0; 7.0] (p = 0.019) and 9.0 [6.8; 8.0] vs. 6.0 [5.0; 8.0] (p = 0.012), respectively. Newborns with EONS in 2021 compared with 2018 showed a significant increase in norepinephrine administration of (42/47 vs. 16/26 newborns, respectively; OR = 5.25; 95 % CI = 1.58–17.44; p = 0.007), FFP transfusions (47/47 vs. 19/26 newborns, respectively; OR = 36.54; 95 % CI = 2.05–649.84; p &lt; 0.001) and surfactant therapy (32/47 vs. 7/26 newborns, respectively; OR = 5.79; 95 % CI = 2.04–16.45; p = 0.001). Mortality among patients with EONS in 2021 compared to 2018 was significantly higher: 13/47 (21.3 %) vs. 2/26 (7.7 %) newborns, respectively (OR = 9.56; 95 % CI = 1.22–74.96; p = 0.014). Conclusion. Among the newborns of the Kaluga region there is a significant rise in the incidence and mortality of EONS on the background of the COVID-19 pandemic. In 2021 there is a significant increase in the need for surfactant administration, use of vasopressors, and transfusion of FFP in infants with EONS.

Hemodynamic maintenance with norepinephrine in caesarean section under spinal anesthesia and its fetal outcome: a systematic review

Background: Postspinal hypotension is a frequent maternal complication in caesarean delivery under neuraxial anesthesia. Anesthesiologists have been using different vasopressors to maintain hemodynamics. Recent studies suggested beneficial effects of norepinephrine on maternal blood pressure and cardiac output, but little evidence exist on the neonatal outcome. Objectives: This systematic review summarises recent evidence on neonatal outcome, such as umbilical arterial pH and base excess, after administration of norepinephrine during caesarean section. Methods: A literature search on PubMed from 2010 to 2022 was performed and every article was reviewed on neonatal outcome, as primary endpoint and on maternal hemodynamics, as secondary endpoint. A total of 15 randomised controlled trials were included. Results: Studies using a prophylactic infusion of norepinephrine show normal fetal blood gases. No evidence of fetal stress (pH &lt; 7,20, base excess &lt; -6) was assessed in the studies. Norepinephrine succeed in maintaining maternal hemodynamics. It is responsible for less bradycardia than phenylephrine and less tachycardia than ephedrine. Conclusion: Our study suggests that norepinephrine, preferably as prophylactic infusion, is a safe vasopressor to prevent postspinal hypotension in caesarean section. No signs of fetal acidosis could be demonstrated in the recent studies.

Predictors of successful weaning from VA-ECMO: the role of CS etiology and related treatment

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a short-term mechanical circulatory support for refractory cardiogenic shock (CS). Successful weaning from VA ECMO is defined as device removal without further requirement for re-cannulation over the following 30 days. Few data exist regarding timing and reliable parameters for weaning from VA-ECMO: most study focused on echocardiographic and invasively monitored parameters during weaning trial(1,2). No data exist concerning pharmacological support and standard haemodynamic parameters in the first 24 hours since VA-ECMO implantation. Purpose We sought to evaluate hemodynamic predictors of VA-ECMO weaning. Methods Single-center retrospective observational study of patients with refractory CS who underwent VA-ECMO insertion from 2013 to 2020 in Intensive Care Unit (ICU). Primary endpoint was successful weaning from VA ECMO. Demographic, clinical, hemodynamic data within the first 24 hours and outcome were collected. We also recorded maximum dose of each vasoactive medication, Vasoactive Inotropic Score (VIS)(3) after VA-ECMO implantation and the total amount of time exposition to vasoactive drugs. Results 100 patients (26% female; 52,6±12,6 y.o.) who underwent VA-ECMO cannulation were enrolled (Table 1). 31 were successfully weaned (31%) at a median time of 140,0 [74,3-229,0] hours; 30-days mortality was 47%. 79 (79%) patients were admitted for cardiac arrest (CA); 48 (48%) had acute myocardial infarction (AMI)-CS. CA patients were less likely to be weaned: 20,3% of CA patients had successful VA-ECMO removal while 79,4% was not weaned (p &amp;lt;0,001). In the weaned group, mean blood pressure was significantly higher (75,3±18,2 vs 61,4±18,3 mmHg; p &amp;lt;0,01).Patients who successfully removed VA-ECMO had lower serum lactate (8,8±5,2 vs 11,3±5,0 mmol/L; p &amp;lt;0,05), lower fluid balance (+2,3 [0,5-5,5] vs +4,1 [1,7-8,3] L/die; p &amp;lt;0,05) and lower Sequential Organ Failure Assessment (SOFA) score (11,2±2,6 vs 13,2±3,4; p &amp;lt;0,01). Lower doses of norepinephrine was administered in patient successfully weaned (0,27±0,17 vs 0,44±0,25 mcg/kg/min; p &amp;lt;0,01). Despite not significant, lower VIS and time to exposition to vasoactive drugs amongst weaned patients were observed (p=0,08 and p=0,09, respectively). Stepwise logistic regression confirmed the worst outcome of CA patients (OR 0,64; p &amp;lt;0,001), SOFA score (OR 0,81; p &amp;lt;0,05) and time to exposition to vasoactive drugs (OR 0,81; p &amp;lt;0,05) on successful weaning from VA-ECMO. Conclusions Mortality of patients undertaking VA-ECMO still remains high. Amongst the data in the model, the strongest negative association with successful weaning from VA-ECMO was found for CA, according to the latest classification entailing CA as CS severity modifier(4). Other results show higher requirement of norepinephrine and fluid administration for vasoplegia mostly related to hypoxic organ injury and related infection (i.e. bowel translocation).

Psychological stress triggers the accumulation of myeloid-derived suppressor cells in the liver through adrenergic receptor signaling

Abstract Chronic physiological stress affects tightly regulated crosstalk between the nervous and the immune system. However, the exact mechanism(s) of stress-induced immunomodulation is far from clear. Immature myeloid cells such as myeloid-derived suppressor cells (MDSCs) impair immune responses, which may in turn increase susceptibility to infections and cancer or their complications. In a mouse model of chronic psychological stress through physical restraint, we found mononuclear-MDSC (Mo-MDSC) cells, defined as CD11b +Ly6C highLy6G highcells, to accumulate in the liver. These cells expressed high levels of Mo-MDSC markers such as CD14, TLR4, IL-4Rα as well as markers indicative of anti-apoptotic and immunosuppressive functions (HIF-1α, G-CSFR, Bcl2, Arg2, iNOS). In addition, FACS sorted MDSCs suppressed production of IFN-ɣ by T cells in vitro. Increased levels of proinflammatory mediators were detectable in serum samples of stressed mice, with circulating levels of IL-6 and G-CSF being the most pronounced mediators. The observed intrahepatic accumulation of Mo-MDSC-like cells was mediated by IL-6 and G-CSF and could be reversed by treatment with corresponding receptor-blocking monoclonal antibodies. In addition, this phenomenon was driven by norepinephrine (NE), the main neurotransmitter released from sympathetic neurons, and could be recapitulated by in vivo administration of NE to non-stressed mice. Our work reveals a novel mechanism of immunosuppression that is governed by adrenergic and inflammatory cues and alters the cellular landscape of the liver with implications for immune surveillance against microbes and cancer. This work was funded by NSERC

Comparison Between Norepinephrine-Epinephrine and Norepinephrine-Vasopressin Effectiveness in Reducing Mortality in Septic Shock: A Systematic Review

&lt;div class="page" title="Page 1"&gt;&lt;div class="layoutArea"&gt;&lt;div class="column"&gt;&lt;p&gt; &lt;/p&gt;&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Sepsis is a state of organ dysfunction caused by the immune system’s abnormal response to an infection. Septic shock is sepsis complicated by circulatory and metabolic abnormalities, oftentimes resulting in death. Prompt identification and treatment of septic shock is crucial for the survival of patients. The latest international guideline recommends the administration of norepinephrine as the first line vasopressor, with the addition of epinephrine or vasopressin as an aid in achieving the target MAP (Mean Arterial Pressure).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study is a systematic review of literatures from the databases Pubmed PMC, Science Direct, and Proquest. Systematic reviews on septic shock, norepinephrine, and epinephrine or vasopressin were among the inclusion criterias. This resulted in a total of five systematic reviews to be included in the qualitative synthesis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The five included studies were not in sync as to which vasopressor is best used for the treatment of septic shock patients. One of which did not compare the two combinations within the same category, two of which favored the use of norepinephrine-epinephrine, and the other two favored the use of norepinephrine-vasopressin for the treatment of septic shock patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The existing evidence were insufficient to give a conclusion of the best combination of vasopressors for septic shock patients. More research, specifically randomized controlled trials, needs to be conducted on this topic with well defined administration of combinations of vasopressors as an advancement of this systematic review. The writers also recommend the delay of anymore systematic reviews until the former recommendation has been met.&lt;/p&gt;&lt;/div&gt;&lt;/div&gt;&lt;/div&gt;

Prophylactic Administration with Methylene Blue Improves Hemodynamic Stabilization During Obstructive Jaundice–Related Diseases’ Operation: a Blinded Randomized Controlled Trial

ObjectivesPatients with obstruction jaundice are at a high risk of hypotension and need high volume of fluids and a high dose of catecholamine to maintain organ perfusion during operation procedure. All these likely contribute to high perioperative morbidity and mortality. The aim of the study is to evaluate the effects of methylene blue on the hemodynamics in patients undergoing surgeries associated with obstructive jaundice. DesignA prospective, randomized, and controlled clinical study. SettingThe enrolled patients randomly received 2 mg/kg of methylene blue in saline or saline (50 ml) before anesthesia induction. The primary outcome was the frequency and dose of noradrenaline administration to maintain mean arterial blood pressure over 65 mmHg or > 80% of baseline, and systemic vascular resistance (SVR) over 800 dyne/s/cm5 during operation. The secondary outcomes were liver and kidney functions, and ICU stay. PatientsSeventy patients were enrolled in the study and randomly assigned to receive either methylene blue or control (n = 35/group). ResultsFewer patients received noradrenaline in the methylene blue group when compared with the control group (13/35 vs 23/35, P = 0.017), and the noradrenaline dose administrated during operation was reduced in the methylene blue group when compared with the control group (0.32±0.57 mg vs 1.787±3.51 mg, P = 0.018). The blood level of creatinine, glutamic oxalacetic transaminase, and glutamic–pyruvic transaminase after the operation was reduced in the methylene blue group when compared with the control group. ConclusionsProphylactic administration of methylene blue before operation associated with obstructive jaundice improves hemodynamic stability and short-term prognosis. QuestionMethylene blue use prevented refractory hypotension during cardiac surgery, sepsis, or anaphylactic shock. It is still unknown that methylene blue on the vascular hypo-tone associated with obstructive jaundice. FindingsProphylactic administration with methylene blue improved peri-operative hemodynamic stability, and hepatic and kidney function on the patients with obstructive jaundice. MeaningsMethylene blue is a promising and recommended drug for the patients undergoing the surgeries of relief obstructive jaundice during peri-operation management.

Mechanism of Increased Spinal Cord Blood Flow due to Noradrenaline Administration Using Vascular Resistance: An Experimental Study Using a Canine Model

During thoracoabdominal aortic surgery, the spinal cord is placed under ischemic conditions. Elevation of systemic blood pressure is thus recommended as a method of increasing the blood supply from collateral networks. This study examined the mechanisms by which noradrenaline administration increases spinal cord blood flow (SCBF) by elevating systemic blood pressure. In beagles (n = 7), the thoracoabdominal aorta and L2-L7 spinal cord segmental arteries (SAs) were exposed and a distal perfusion bypass was created to simulate clinical practice. SCBF was measured by laser flowmetry at the L5 dura mater and spinal cord perfusion pressure (SCPP) was measured inside the clamped aorta. The six pairs of SAs from L2 to L7 were clamped, and mean systemic blood pressure (mSBP), SCBF, and SCPP were measured before and after clamping and after starting continuous infusion of noradrenaline at 0.5 µg/kg/min. Rates of change in systemic vascular resistance (SVR) and spinal cord vascular resistance (SCVR) were calculated from the measured values. With no SA clamping (control), the rate of increase in SCVR was 0.74 times the rate of increase in SVR (y = 0.2 + 0.74x, r = 0.889, r2 = 0.789; P < 0.01). When all six pairs of SAs were clamped, a weak correlation was evident between rate of change in SCVR and rate of change in SVR, and the rate of increase in SCVR was lower than the rate of increase in SVR (y = 0.39 + 0.07x, r = 0.209, r2 = 0.039; P < 0.01). When all six pairs of SAs were clamped in the absence of distal perfusion, a weak correlation was also evident between rate of change in SCVR and rate of change in SVR, and the rate of increase in SCVR was lower than the rate of increase in SVR (y = 0.19 + 0.08x, r = 0.379, r2 = 0.144; P < 0.01). The rate of increase in SCVR induced by noradrenaline administration was lower than the rate of increase in SVR in the control group with no spinal cord SA clamping and in both experimental groups with clamped SAs (with and without distal perfusion), creating an environment conducive to spinal cord flow distribution.

Influence of time from admission to norepinephrine administration and volume of fluids received on outcomes of patients meeting sepsis-3 criteria: a retrospective study using the MIMIC-IV database

ObjectivesVasopressors are a cornerstone in the management of sepsis, marked by distributive shock often unresponsive to fluid resuscitation. Prior research and clinician surveys have suggested that earlier usage of vasopressors...

The impact of early norepinephrine administration on outcomes of patients with sepsis induced hypotension, randomized controlled prospective study

The impact of early norepinephrine administration on outcomes of patients with sepsis induced hypotension, randomized controlled prospective study

Investigating the relationship between high-dose norepinephrine administration and the incidence of delayed cerebral infarction in patients with aneurysmal subarachnoid hemorrhage: A single-center retrospective evaluation.

One of the longest-standing treatments to prevent delayed cerebral infarction (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) remains raising the blood pressure to a certain level of mean arterial pressure. This may require high doses of norepinephrine, which has been associated with severe end organ damage. With this study, we aimed to investigate the effects of norepinephrine on the incidence of DCI in a clinical setting. We conducted a retrospective evaluation of patients with aSAH admitted to our institution between November 2018 and March 2021. Potential risk factors for DCI were analyzed and significant predictors were assessed by means of a logistic regression analysis to account for potential confounders. In this study, 104 patients were included. Hereof, 39 (38%) showed radiologic signs of DCI between day three and 14 post-intervention. These patients had more frequent vasospasms (n = 37 vs. 30, p = 0.022), a higher Hunt & Hess score (3 ± 2 vs. 2 ± 1, p = 0.004), a lower initial Glasgow Coma Scale score (9 ± 5 vs. 12 ± 4, p = 0.003) and received a higher median norepinephrine dose (20,356μg vs. 6,508μg, p < 0.001). A logistic regression analysis revealed that only high-dose norepinephrine administration (OR 2.84, CI 1.56-7.8) and vasospasm (OR 3.07, CI 1.2-7.84) appeared to be significant independent risk factors for DCI. Our results indicate a significant association between higher dose norepinephrine administration and the occurrence of DCI. Future research including greater sample sizes and a prospective setting will be necessary to further investigate the relationship.

Incidence of bradycardia during noradrenaline or phenylephrine bolus treatment of postspinal hypotension in cesarean delivery: A randomized double-blinded controlled trial.

The treatment of choice for spinal anesthesia-induced hypotension during cesarean section is phenylephrine. As this vasopressor can cause reflex bradycardia, noradrenaline is a suggested alternative. This randomized double-blinded controlled trial included 76 parturients undergoing elective cesarean delivery under spinal anesthesia. Women received noradrenaline in bolus doses of 5mcg or phenylephrine in bolus doses of 100 mcg. These drugs were used intermittently and therapeutically to maintain systolic blood pressure ≥ 90% of its baseline value. The primary study outcome was bradycardia incidence (<60 bpm) with intermittent bolus administration of these drugs. Secondary outcomes included extreme bradycardia (<40 bpm), number of bradycardia episodes, hypertension (systolic blood pressure > 120% of baseline value), and hypotension (systolic blood pressure < 90% of baseline value and requiring vasopressor use). Neonatal outcomes per the Apgar scale and umbilical cord blood gas analysis were also compared. The incidence of bradycardia in both groups (51.4% and 70.3%, respectively; p=0.16) were not significantly different. No neonates had umbilical vein or artery pH values below 7.20. The noradrenaline group required more boluses than phenylephrine group (8 vs. 5; p=0.01). There was no significant intergroup difference in any of the other secondary outcomes. When administered in intermittent bolus doses for the treatment of postspinal hypotension in elective cesarean delivery, noradrenaline, and phenylephrine have a similar incidence of bradycardia. When treating hypotension related to spinal anesthesia in obstetric cases, strong vasopressors are commonly administered, thought these can also have side effects. This trial assessed bradycardia after bolus administration of noradrenaline or phenylephrine, and found no difference in risk for clinically meaningful bradycardia.