Doses Of Norepinephrine Research Articles

Population Pharmacokinetic Modelling of Norepinephrine in Healthy Volunteers Prior to and During General Anesthesia.

Intraoperation hypotension (IOH) is commonly observed in patients undergoing surgery under general anesthesia, and even a brief episode of IOH can lead to unfavorable outcomes. To reduce the risk, blood pressure is closely measured during general anesthesia, and norepinephrine (NE) is frequently administered if hypotension is detected. Despite its routine application, information on the dose-exposure-response relationship of NE remains limited. Additionally, quantification of the influence of general anesthesia on the pharmacokinetics (PK) of NE is lacking. In this study, we aimed to describe NE PK in healthy volunteers and the influence of general anesthesia on its PK. A single-center, cross-over study was conducted in healthy volunteers. The volunteers received a step-up NE dosing scheme (0.04, 0.08, 0.12, 0.16 and 0.20 mcg-1/kg-1/min-1) first in the awake state and then under general anesthesia. General anesthesia was administered using a propofol/remifentanil Eleveld target-controlled infusion. During general anesthesia, a 30-second electrical stimulus was given as surrogate for surgical incision to the volunteers at each dosage step. Blood samples were drawn before the initial dosing and after each dosing step, and plasma NE, propofol and remifentanil concentrations were subsequently determined. A population PK model was developed using non-linear mixed effects modelling. Simulations were conducted to predict the plasma NE concentration in patients at different measured propofol concentrations. A total of 1219 samples were analyzed from 36 volunteers. A two-compartment model with a first-order elimination best described the data. Weight, age, and session effect (awake vs general anesthesia) were identified as relevant covariates on the clearance (CL) of NE. A 10% decrease in NE CL was observed after general anesthesia induction. This difference between sessions is better explained by the measured concentration of propofol, rather than the anticipated impact of cardiac output. The estimated post-stimulation NE concentration is 0.66 nmol/L-1 (95% CI 0.06-1.20 nmol/L-1) lower than the pre-stimulation NE concentration. Model simulation indicates that patients at a higher measured propofol concentration (e.g., 6 mcg/mL-1) exhibited higher NE concentrations (95% PI 18.10-43.89 nmol/L-1) than patients at a lower measured propofol concentration (e.g., 3 mcg/mL-1) (95% PI 16.81-38.91 nmol L-1). The NE PK is well described with a two-compartment model with a first-order elimination. NE CL exhibiting a 10% decrease under general anesthesia, with this difference being attributed to the measured concentration of propofol. The impact of stimulation on NE PK under general anesthesia is very limited. NL9312.

An Observational Study on Clinical Benefits of CytoSorb in Patients with Severe Sepsis

Background and Aim: Sepsis is a well-recognized healthcare issue worldwide. Despite research, the ability to positively influence outcome remains limited. Newer evidences have pointed that using adsorption of cytokines is beneficial during endotoxemia and sepsis. Therefore, this study was aimed to determine the clinical benefits of CytoSorb usage in patients with severe sepsis admitted in intensive care units (ICU). Study Design: Prospective, observational, comparative study. Material and Methods: Forty patients with sepsis admitted to ICU were included. The CytoSorb group included 20 patients who received CytoSorb therapy in addition to Standard-care (SOC) and 20 patients in SOC group who received SOC alone as per routine ICU protocols. Clinical and laboratory parameters were analyzed pre/post-treatment in both groups and compared. Results: CytoSorb and SOC groups were comparable at baseline. There was significant reduction in serum creatinine (2.59±2.0 vs. 2.89±1.2, mg/dl; P=0.042), serum lactate (3.26±1.1 vs. 3.27±0.9, mmol/lit; P<0.001), serum procalcitonin (2.75±2.4 vs. 3.39±3.5, ng/ml; P<0.001), serum CRP (90.2±57.4 vs. 175.6±100.9, mg/dl; P<0.001) and serum IL6 (1769.7±4444.1 vs. 256.8±392.4, pg/ml; P=0.03) levels in CytoSorb compared to SOC. There was significant improvement in mean arterial pressure (MAP) (65.75±1.8 vs. 62.75±2.8, mmHg; P<0.001) and reduction in norepinephrine dose (6.47±2.7 vs.10.65±3.6, mcg/min; P<0.001) in CytoSorb group reflecting better hemodynamic stability. The post-treatment increase in SOFA score was lesser in CytoSorb group (11.85±2.9) than SOC group (12.3±2.3), but was not significant (P=0.135). Conclusion: CytoSorb therapy along with SOC was associated with significant improvements in hemodynamic stability, MAP and Norepinephrine requirements than SOC alone in severe sepsis.

Efficacy and Safety of Ciprofol Versus Propofol as Anesthetic for Patients Undergoing Painless Colonoscopy.

Ciprofol is a novel propofol analogue with a characteristic of hemodynamic stability. At present, there is a lack of research comparing the hemodynamic stability of ciprofol and propofol during painless colonoscopy. In this study, we aim to test the hypothesis that ciprofol is superior to propofol in terms of hemodynamic stability for sedation anesthesia in patients undergoing colonoscopy. A total of 222 patients were randomized into two groups. Patients in group P (n=112) and group C (n=110) received propofol and ciprofol sedation, respectively. Noninvasive blood pressure were monitored starting from induction (T0) to the end of the procedure, at 2-min intervals (T1 to T10). Heart rate variability (HRV), pain injection, Modified Observer's Assessment of Alertness and Sedation(MOAA/S) score, body movement, doses of norepinephrine, modified Aldrete score, drug-related adverse reactions, and patient satisfaction and endoscopist satisfaction were recorded. In group C, fewer patients experienced a decrease in blood pressure with a higher HRV after induction sedation, the incidence of pain injection was reduced, the amount of norepinephrine dose was decreased, patient satisfaction was increased compared with group P (all P<0.05). There were no significant differences in induction time, modified Aldrete score, alertness time, drug-related adverse reactions, and endoscopist satisfaction. Our study indicated intravenous induction with ciprofol was superior, with regard to hemodynamic stability and reduced injection pain, than induction with propofol for anesthesia in patients undergoing painless colonoscopy. Chinese Clinical Trial Registry (ChiCTR2200061814).

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

Intraoperative Fluid Balance and Perioperative Complications in Ovarian Cancer Surgery.

Fluid overload and hypovolemia promote postoperative complications in patients undergoing cytoreductive surgery for ovarian cancer. In the present study, postoperative complications and anastomotic leakage were investigated before and after implementation of pulse pressure variation-guided fluid management (PPVGFM) during ovarian cancer surgery. A total of n = 243 patients with ovarian cancer undergoing cytoreductive surgery at the University Hospital Bonn were retrospectively evaluated. Cohort A (CA; n = 185 patients) was treated before and cohort B (CB; n = 58 patients) after implementation of PPVGFM. Both cohorts were compared regarding postoperative complications. Ultrasevere complications (G4/G5) were exclusively present in CA (p = 0.0025). No difference between cohorts was observed regarding severe complications (G3-G5) (p = 0.062). Median positive fluid excess was lower in CB (p = 0.001). This was independent of tumor load [peritoneal cancer index] (p = 0.001) and FIGO stage (p = 0.001). Time to first postoperative defecation was shorter in CB (CB: d2 median versus CA: d3 median; p = 0.001). CB had a shorter length of hospital stay (p = 0.003), less requirement of intensive medical care (p = 0.001) and postoperative ventilation (p = 0.001). CB received higher doses of noradrenalin (p = 0.001). In the combined study cohort, there were more severe complications (G3-G5) in the case of a PFE ≥ 3000ml (p = 0.034) and significantly more anastomotic leakage in the case of a PFE ≥ 4000ml (p = 0.006). Intraoperative fluid reduction in ovarian cancer surgery according to a PPVGFM is safe and significantly reduces ultrasevere postoperative complications. PFEs of ≥ 3000ml and ≥ 4000ml were identified as cutoffs for significantly more severe complications and anastomotic leakage, respectively.

Plasma exchange does not improve overall survival in patients with acute liver failure in a real world cohort

Background and AimsTherapeutic plasma exchange (PEX) has emerged as a potential treatment option for patients with acute liver failure (ALF). The effect of PEX on survival outcomes outside of clinical trials is not yet well established. In this study we aimed to evaluate the real-world use and outcomes of PEX for the treatment of ALF. MethodsThis multicentre retrospective cohort study included consecutive patients with ALF admitted to all 7 tertiary liver transplant centres in the United Kingdom (UK) between June 2013 and December 2021. Changes in clinical variables following PEX treatment was assessed and overall survival and transplant free survival (TFS) to hospital discharge of patients receiving PEX were compared to those receiving standard medical therapy (SMT). Propensity score matching was performed to control for intergroup covariates and selection bias. ResultsWe included 378 patients with ALF (median (IQR) age 36 (28-48), 64% (n=242) female) of which 120 received PEX. There was a significant improvement in most clinical variables following PEX, including median dose of noradrenaline (reduction from 0.35 μg/kg/min (0.19 - 0.70 μg/kg/min) to 0.16 μg/kg/min (0.08 - 0.49) (p = 0.001). There was no significant difference between PEX and SMT groups in overall survival (51.4 % v 62.6 % respectively, p = 0.12) or TFS (42.6 % v 53.1 %, p = 0.24). ConclusionPEX is now frequently used in the management of ALF patients in the UK. It is associated with significant improvement in haemodynamic parameters but there is no survival benefit. Impact and implicationsPEX is frequently used in the management of patients with ALF in the UK. This real-world study demonstrates significant improvement in haemodynamic status but has not confirmed the survival benefit seen in previous published literature. These results should help inform future use of PEX.

Opioid-free anesthesia attenuates perioperative immunosuppression by regulating macrophages polarization in gastric cancer patients treated with neoadjuvant PD-1 inhibitor.

Opioid anesthesia can modulate the impaired immune response and opioid-sparing anesthesia may preserve immune functions. This study was performed to assess the effects of opioid-free anesthesia (OFA) and opioid-based anesthesia (OA) on perioperative macrophages differentiation, cytokine changes, and perioperative complications in locally advanced GC (LAGC) patients. We used quality of recovery-15 (QoR-15) questionnaire scores and visual analog scale (VAS) scores to compare postoperative quality of recovery and pain level. In addition, the adverse reactions of patients in the two groups were compared. The perioperative serum level of inflammatory cytokines and the ratio of macrophage subtypes were detected. The OFA group had significantly longer extubation time and PACU stay, whereas the OA group had significantly higher rate of hypotension, higher doses of norepinephrine, higher PONV and dizziness rate, and delayed flatus passage time. The QoR-15 score on postoperative 24 h was significantly higher in OFA group than in OA group. At the end of or after the surgery, the OFA group had higher levels of interleukin (IL)-12, IL-1β, tumor necrosis factor (TNF)-α, CD68+CD163- macrophage rate, but lower levels of IL-10, transforming growth factor (TGF)-β, and CD68+CD163+ macrophage rate, indicating OFA attenuated perioperative immunosuppression by diminishing M2 and promoting M1 macrophage polarization. And the reversal tendency is more obvious in LAGC patients with neoadjuvant PD-1 inhibitor. The OFA may attenuate perioperative immunosuppression by diminishing M2 and promoting M1 macrophage polarization in LAGC patients with neoadjuvant PD-1 inhibitor. http://gcpgl.sysucc.org.cn, identifier 2022-FXY-001.

The role of esmolol in sepsis: a meta-analysis based on randomized controlled trials

BackgroundSepsis is associated with a high incidence and mortality and poses a significant challenge to the treatment. Although esmolol has shown promise in sepsis treatment, its efficacy and safety remain contentious. This meta-analysis aims to clarify the role of esmolol in sepsis management.MethodsPubMed, Embase, Web of Science, Cochrane library, clinicaltrials.gov and the Chinese Clinical Trial Registry were searched and references of relevant reviews and meta-analysis were also screened for appropriate studies. Keywords and free words of ‘sepsis’, ‘esmolol’ and ‘randomized controlled trials’ were used for search. Meta-analysis was performed using RevMan 5.3 software.ResultsFifteen studies involving 1100 patients were included. Compared with the control group, patients receiving esmolol exhibited significantly decreased 28-day mortality (RR, 0.69; 95% CI, 0.60 to 0.81; P < 0.0001), heart rate (HR) (SMD, -1.15; 95% CI, -1.34 to -0.96; P < 0.0001), cardiac troponin I levels (cTnI) (SMD, -0.88; 95% CI, -1.13 to -0.64; P < 0.0001), length of intensive care unit (ICU) stay (SMD, -0.46; 95% CI, -0.62 to -0.3; P < 0.0001) and duration of mechanical ventilation (SMD, -0.28; 95% CI, -0.48 to -0.09; P = 0.004) and significantly increased central venous oxygen saturation (ScvO2) (SMD, 0.66; 95% CI, 0.44 to 0.88; P < 0.0001).While, esmolol had no significant influence on norepinephrine dosage (SMD, 0.08; 95% CI, -0.13 to 0.29; P = 0.46), mean arterial pressure (MAP) (SMD, 0.17; 95% CI, -0.07 to 0.4; P = 0.16), central venous pressure (CVP) (SMD, 0.16; 95% CI, -0.04 to 0.35; P = 0.11) and left ventricular ejection fraction (LVEF) (SMD, 0.21; 95% CI, -2.9 to 0.7; P = 0.41).ConclusionEsmolol reduces 28-day mortality, length of ICU stay and duration of mechanical ventilation in sepsis patients. Furthermore, esmolol improves oxygen metabolism, mitigates myocardial injury and decreases heart rate without significantly affecting hemodynamic parameters.Trial registrationThis study was registered on the PROSPERO website (registration number: CRD42023484884).

Efficacy of HA380 hemoperfusion in the treatment of septic shock

Background: To evaluate the clinical efficacy of HA380 hemoperfusion (HP) in the treatment of septic shock. Methods: This study retrospectively analyzed the clinical data of patients with septic shock admitted to Ward II of the Department of Critical Care Medicine at the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2022 to December 2023. These data included general information, temperature, heart rate (HR), mean arterial pressure (MAP), oxygenation index, norepinephrine (NE) dose, lactic acid, white blood cell count, neutrophil percentage, lymphocyte absolute value, procalcitonin (PCT), interleukin-6 (IL-6), acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA) before and after each blood perfusion (HA380), total hospital stay, intensive care unit (ICU) stay, and 28-day survival. Results: A total of 41 patients with septic shock were included in this study, consisting of 38 males and 3 females. According to their primary diseases, there were 18 cases of severe pneumonia, 16 cases of abdominal infection, 4 cases of bloodstream infection, 2 cases of urinary infection, and 1 case of soft tissue infection. At the time of inclusion, 33 patients underwent mechanical ventilation for respiratory support, and 4 patients were treated with extracorporeal membrane oxygenation. Statistically significant differences (all P &lt; 0.05) were observed in body temperature, HR, MAP, oxygenation index, norepinephrine dose, lactic acid, PCT, IL-6, creatinine (Cr), APACHE II, and SOFA before and after HP (HA380) treatment. According to the 28-day survival status of patients, patients were allocated into survival and death groups. The total hospital stay and ICU stay were statistically significantly different between the two groups (all P &lt; 0.05). Additionally, there were also statistically significant differences in APACHE II and SOFA before and after treatment (all P &lt; 0.05). Based on the severity stratification of IL-6 and PCT levels, it was observed that following HP (HA380) treatment, all subgroups showed varying degrees of improvement in SOFA and APACHE II scores (P &lt; 0.05). Conclusion: HP (HA380) can improve the clinical efficacy of patients with septic shock. In addition, this method improves hemodynamics, effectively reduces lactic acid levels and infection indexes, and alleviates organ function damage in patients with septic shock, which can strive for more time for subsequent treatment.

Lower or Higher Oxygenation Targets in Patients With COVID-19 in the ICU: A Secondary Bayesian Analysis of the Handling Oxygenation Targets in COVID-19 Trial

BackgroundIn the Handling Oxygenation Targets in COVID-19 (HOT-COVID) trial, a partial pressure of arterial oxygen (PaO2) target of 60 mmHg compared to 90 mmHg resulted in more days alive without life support at 90 days in adult ICU patients with coronavirus disease 2019 (COVID-19) and hypoxemia. The trial was stopped after enrolling 726 of 780 planned patients due to slow recruitment. Here, we present the preplanned Bayesian analysis of the HOT-COVID trial. Research QuestionWhat are the probabilities of any and of clinically relevant benefits from a PaO2 target of 60 mmHg versus 90 mmHg in adult ICU patients with COVID-19 and hypoxemia, and is there heterogeneity of treatment effects (HTE) according to selected baseline characteristics? Study Designand Methods We analyzed days alive without life support and 90-day mortality in the HOT-COVID intention-to-treat population (n=697) using Bayesian general linear models to assess probabilities for benefit or harm, including clinically relevant benefits defined as >1 day alive without life support and >2 percentage points lower 90-day mortality. HTE was evaluated based on baseline SOFA scores, PaO2:FiO2, norepinephrine doses, and lactate concentrations. ResultsThe mean difference in days alive without life support was 5.7 days (95% credible interval (CrI): 0.2 to 11.2), with a 95.2% probability of clinically relevant benefit and a 98.0% probability of any benefit from the lower PaO2 target. The risk difference in 90-day mortality was -4.6 percentage points (95% CrI: -11.8 to 2.6), with a 76.5% probability of a clinically relevant benefit from the lower target. HTE analyses revealed potential interaction with baseline norepinephrine dose and lactate concentrations for both outcomes. InterpretationIn ICU patients with COVID-19 and hypoxemia, we found high probability for a clinically relevant benefit of targeting a PaO2 of 60 mmHg vs. 90 mmHg on number of days alive without life support.

Noradrenaline dose cutoffs to characterise the severity of cardiovascular failure: Data-based development and external validation.

The vasopressor dose needed is a common measure to assess the severity of cardiovascular failure, but there is no consensus on the ranges of vasopressor doses determining different levels of cardiovascular support. We aimed to identify cutoffs for determining low, intermediate and high doses of noradrenaline (norepinephrine), the primary vasopressor used in intensive care, based on association with hospital mortality. We conducted a binational registry study to determine cutoffs between low, intermediate and high noradrenaline doses. We required the cutoffs to be statistically rational and practical (rounded to the first decimal and easy to remember), and to result in increasing mortality with increasing doses. The highest noradrenaline dose in the first 24 h after intensive care unit (ICU) admission was used. The cutoffs were developed using data from 8079 ICU patients treated in the ICU at Kuopio University Hospital, Finland, between 2013 and 2019. Subsequently, the cutoffs were validated in the eICU database, including 39,007 ICU admissions to 29 ICUs in the United States of America in 2014-2015. The log-rank statistic, with the Contal and O'Quigley method, was used to determine the cutoffs resulting in the most significant split between the noradrenaline dose groups with regard to hospital mortality. The two most prominent peaks in the log-rank statistic corresponded to noradrenaline doses 0.20 and 0.44 μg/kg/min. Accordingly, we determined three dose ranges: low (<0.2 μg/kg/min), intermediate (0.2-0.4 μg/kg/min) and high (>0.4 μg/kg/min). Mortality increased, whereas the number of patients decreased consistently with increasing noradrenaline doses in both cohorts. In the development cohort, hospital mortality was 6.5% in the group without noradrenaline administered and 14.0%, 26.4% and 40.2%, respectively, in the low-dose, intermediate-dose and high-dose groups. Compared to patients who received no noradrenaline, the hazard ratio for in-hospital death was 1.4 for the low-dose group, 4.0 for the intermediate-dose group and 7.5 for the high-dose group in the validation cohort (p < .001). The highest noradrenaline dose is a useful measure for quantifying circulatory failure. Cutoffs 0.2 and 0.4 μg/kg/min seem to be suitable for defining low, intermediate and high doses.

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.

Fluid boluses and infusions in the early phase of resuscitation from septic shock and sepsis-induced hypotension: a retrospective report and outcome analysis from a tertiary hospital

BackgroundFluid administration is the first line treatment in intensive care unit (ICU) patients with sepsis and septic shock. While fluid boluses administration can be titrated by predicting preload dependency, the amount of other forms of fluids may be more complex to be evaluated. We conducted a retrospective analysis in a tertiary hospital, to assess the ratio between fluids given as boluses and total administered fluid intake during early phases of ICU stay, and to evaluate the impact of fluid strategy on ICU mortality. Data related to fluid administration during the first four days of ICU stay were exported from an electronic health records system (ICCA®, Philips Healthcare). Demographic data, severity score, norepinephrine dose at ICU admission, overall fluid balance and the percentage of different fluid components of the overall volume administered were included in a multivariable logistic regression model, evaluating the association with ICU survival.ResultsWe analyzed 220 patients admitted with septic shock and sepsis-induced hypotension from 1st July 2021 to 31st December 2023. Fluid boluses and maintenance represented 49.3% ± 22.8 of the overall fluid intake, being balanced solution the most represented (40.4% ± 22.0). The fluid volume for drug infusion represented 34.0% ± 2.9 of the total fluid intake, while oral or via nasogastric tube fluid intake represented 18.0% ± 15.7 of the total fluid intake. Fluid volume given as boluses represented 8.6% of the total fluid intake over the four days, with a reduction from 25.1% ± 24.0 on Day 1 to 4.8% ± 8.7 on Day 4. A positive fluid balance [OR 1.167 (1.029–1.341); p = 0.021] was the most important factor associated with ICU mortality. Non-survivors (n = 66; 30%) received a higher amount of overall inputs than survivors only on Day 1 [2493 mL vs. 1855 mL; p = 0.022].ConclusionsThis retrospective analysis of fluids given over the early phases of septic shock and sepsis-induced hypotension showed that the overall volume given by boluses ranges from about 25% on Day 1 to about 5% on Day 4 from ICU admission. Our data confirms that a positive fluid balance over the first 4 days of ICU is associated with mortality.

COMPARISON OF OXIRIS AND CONVENTIONAL CONTINUOUS RENAL REPLACEMENT THERAPY IN MANAGING SEVERE ABDOMINAL INFECTIONS: IMPACT ON SEPTIC SHOCK MORTALITY.

Objective: The objective of this study is to assess and compare the efficacy of oXiris with conventional continuous renal replacement therapy (CRRT) in managing severe abdominal infections. Methods: A retrospective analysis encompassing cases from 2017 to 2023 was conducted at the Department of Critical Care Medicine within the First Affiliated Hospital of Fujian Medical University. Parameters including heart rate (HR), mean arterial pressure (MAP), oxygenation index, lactate (Lac), platelet count, neutrophil ratio, procalcitonin, C-reactive protein (CRP), interleukin 6 (IL-6), norepinephrine dosage, Acute Physiology and Chronic Health Evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA) were recorded prior to treatment initiation, at 24 h, and 72 h after treatment for both the oXiris and conventional CRRT groups. In addition, the duration of respiratory support, CRRT treatment, length of stay in the intensive care unit (ICU), total hospitalization period, and mortality rates at 14 and 28 days for both groups were recorded. Results: 1) Within the conventional CRRT group, notable enhancement was observed solely in Lac levels at 24 h after treatment compared with pretreatment levels. In addition, at 72 h after treatment, improvements were evident in HR, Lac, CRP, and IL-6 levels. 2) Conversely, the oXiris group exhibited improvements in HR, MAP, Lac, oxygenation index, neutrophil ratio, and IL-6 at 24 h after treatment when compared with baseline values. In addition, reductions were observed in APACHE II and SOFA scores. At 72 h after treatment, all parameters demonstrated enhancement except for platelet count. 3) Analysis of the changes in the indexes (Δ) between the two groups at 24 h after treatment revealed variances in HR, MAP, Lac, norepinephrine dosage, CRP levels, IL-6 levels, APACHE II scores, and SOFA scores. 4) The Δ indexes at 72 h after treatment indicated more significant improvements following oXiris treatment for both groups, except for procalcitonin. 5) The 14-day mortality rate (24.4%) exhibited a significant reduction in the oXiris group when compared with the conventional group (43.6%). However, no significant difference was observed in the 28-day mortality rate between the two groups. 6) Subsequent to multifactorial logistic regression analysis, the results indicated that oXiris treatment correlated with a noteworthy decrease in the 14-day and 28-day mortality rates associated with severe abdominal infections, by 71.3% and 67.6%, respectively. Conclusion: oXiris demonstrates clear advantages over conventional CRRT in the management of severe abdominal infections. Notably, it reduces the fatality rates, thereby establishing itself as a promising and potent therapeutic option.

Physiological effects and safety of bed verticalization in patients with acute respiratory distress syndrome

BackgroundTrunk inclination in patients with Acute Respiratory Distress Syndrome (ARDS) in the supine position has gained scientific interest due to its effects on respiratory physiology, including mechanics, oxygenation, ventilation distribution, and efficiency. Changing from flat supine to semi-recumbent increases driving pressure due to decreased respiratory system compliance. Positional adjustments also deteriorate ventilatory efficiency for CO2 removal, particularly in COVID-19-associated ARDS (C-ARDS), indicating likely lung parenchyma overdistension. Tilting the trunk reduces chest wall compliance and, to a lesser extent, lung compliance and transpulmonary driving pressure, with significant hemodynamic and gas exchange implications.MethodsA prospective, pilot physiological study was conducted on early ARDS patients in two ICUs at CHU Clermont-Ferrand, France. The protocol involved 30-min step gradual verticalization from a 30° semi-seated position (baseline) to different levels of inclination (0°, 30°, 60°, and 90°), before returning to the baseline position. Measurements included tidal volume, positive end-expiratory pressure (PEEP), esophageal pressures, and pulmonary artery catheter data. The primary endpoint was the variation in transpulmonary driving pressure through the verticalization procedure.ResultsFrom May 2020 through January 2021, 30 patients were included. Transpulmonary driving pressure increased slightly from baseline (median and interquartile range [IQR], 9 [5–11] cmH2O) to the 90° position (10 [7–14] cmH2O; P < 10–2 for the overall effect of position in mixed model). End-expiratory lung volume increased with verticalization, in parallel to decreases in alveolar strain and increased arterial oxygenation. Verticalization was associated with decreased cardiac output and stroke volume, and increased norepinephrine doses and serum lactate levels, prompting interruption of the procedure in two patients. There were no other adverse events such as falls or equipment accidental removals.ConclusionsVerticalization to 90° is feasible in ARDS patients, improving EELV and oxygenation up to 30°, likely due to alveolar recruitment and blood flow redistribution. However, there is a risk of overdistension and hemodynamic instability beyond 30°, necessitating individualized bed angles based on clinical situations.Trial registration ClinicalTrials.gov registration number NCT04371016, April 24, 2020.

Early risk predictors of acute kidney injury and short-term survival during Impella support in cardiogenic shock

Acute kidney injury (AKI) is one of the most frequent and prognostic-relevant complications of cardiogenic shock (CS) complicating myocardial infarction (MI). Mechanical circulatory assist devices (MCS) like left ventricular Impella microaxial pump have increasingly been used in the last decade for stabilization of hemodynamics in those patients. Moreover, a protective effect of Impella on renal organ perfusion could recently be demonstrated. However, data identifying early risk predictors for developing AKI during Impella support in CS are rare. Data of hemodynamics and renal function from 50 Impella patients (January 2020 and February 2022) with MI-related CS (SCAI stage C), were retrospectively analyzed using e.g. multivariate logistic regression analysis as well as Kaplan–Meier curves and Cox regression analysis. 30 patients (60%) developed AKI. Central venous pressure as an indicator for venous congestion (OR 1.216, p = 0.02), GFR at admission indicating existing renal damage (OR 0.928, p = 0.002), and reduced central venous oxygen saturation (SvO2) as a marker for decreased tissue perfusion (OR 0.930, p = 0.029) were independently associated with developing an AKI. The 30-day mortality rate was significantly higher in patients with AKI stage 3 (Stage 1: 0%, Stage 2: 0%, Stage 3; 41.6%, p = 0.014) while AKI stage 3 (HR 0.095, p = 0.026) and norepinephrine dosage (HR 1.027, p = 0.008) were independent predictors for 30-day mortality. AKI as a complication of MI-related CS occurs frequently with a major impact on prognosis. Venous congestion, reduced tissue perfusion, and an already impaired renal function are independent predictors of AKI. Thus, timely diagnostics and a focused treatment of the identified factors could improve prognosis and outcome.

Effects of dynamic versus static parameter-guided fluid resuscitation in patients with sepsis: A randomized controlled trial.

Fluid resuscitation is an essential component for sepsis treatment. Although several studies demonstrated that dynamic variables were more accurate than static variables for prediction of fluid responsiveness, fluid resuscitation guidance by dynamic variables is not standard for treatment. The objectives were to determine the effects of dynamic inferior vena cava (IVC)-guided versus (vs.) static central venous pressure (CVP)-guided fluid resuscitation in septic patients on mortality; and others, i.e., resuscitation targets, shock duration, fluid and vasopressor amount, invasive respiratory support, length of stay and adverse events. A single-blind randomized controlled trial was conducted at Thammasat University Hospital between August 2016 and April 2020. Septic patients were stratified by acute physiologic and chronic health evaluation II (APACHEII) <25 or ≥25 and randomized by blocks of 2 and 4 to fluid resuscitation guidance by dynamic IVC or static CVP. Of 124 patients enrolled, 62 were randomized to each group, and one of each was excluded from mortality analysis. Baseline characteristics were comparable. The 30-day mortality rates between dynamic IVC vs. static CVP groups were not different (34.4% vs. 45.9%, p=0.196). Relative risk for 30-day mortality of dynamic IVC group was 0.8 (95%CI=0.5-1.2, p=0.201). Different outcomes were median (interquartile range) of shock duration (0.8 (0.4-1.6) vs. 1.5 (1.1-3.1) days, p=0.001) and norepinephrine (NE) dose (6.8 (3.9-17.8) vs. 16.1 (7.6-53.6) milligrams, p=0.008 and 0.1 (0.1-0.3) vs. 0.3 (0.1-0.8) milligram⋅kilogram -1, p=0.017). Others were not different. Dynamic IVC-guided fluid resuscitation does not affect mortality of septic patients. However, this may reduce shock duration and NE dose, compared with static CVP guidance.

Design of a pharmacokinetic/pharmacodynamic model for administration of low dose peripheral norepinephrine during general anaesthesia.

Intraoperative hypotension is a risk factor for kidney, heart and cognitive postoperative complications. Literature suggests that the use of low-dose peripheral norepinephrine (NOR) reduces organ dysfunction, yet its administration remains unstandardized. In this work we develop a pharmacokinetic (PK)/pharmacodynamic (PD) model of NOR and its effect on mean arterial pressure (MAP). From June 2018 to December 2021, we included patients scheduled for elective neurosurgery and requiring vasopressors for intraoperative hypotension management at Lariboisière Hospital, Paris. Low doses of NOR were administered peripherally, and successive arterial blood samples were collected to track its plasmatic concentration. We used a compartmental modelling approach for NOR PK. We developed and compared 2 models for NOR PD on MAP. Model comparison was done using Bayes information criteria. The resulting PK/PD model parameters were fitted over the entire population and linked to age, weight, height and sex. We included 29 patients (age 52 [46-64] years, 69% female). NOR median time to peak effect on MAP was 74 [53-94] s. After bolus administration, MAP increased by 24% (15-31%). A 2-comparment model with depot best captured NOR PK. NOR PD effect on MAP was well represented by both Emax and Windkessel models, with better results for the former. We found that age, height and weight as well as history of smoking and hypertension were correlated with model parameters. We have developed a PK/PD model to accurately track norepinephrine plasma concentration and its effect on MAP over time, which could serve for target-controlled infusion.

Nitroglycerin versus milrinone for low central venous pressure in patients undergoing laparoscopic hepatectomy: a double-blinded randomized controlled trial

BackgroundConventional anesthesia used to reduce central venous pressure (CVP) during hepatectomy includes fluid restriction and vasodilator drugs, which can lead to a reduction in blood perfusion in vital organs and may counteract the benefits of low blood loss. In this study, we hypothesized that milrinone is feasible and effective in controlling low CVP (LCVP) during laparoscopic hepatectomy (LH). Compared with conventional anesthesia such as nitroglycerin, milrinone is beneficial in terms of intraoperative blood loss, surgical environment, hemodynamic stability, and patients’ recovery.MethodsIn total, 68 patients undergoing LH under LCVP were randomly divided into the milrinone group (n = 34) and the nitroglycerin group (n = 34). Milrinone was infused with a loading dose of 10 µg/kg followed by a maintenance dose of 0.2–0.5 µg/kg/min and nitroglycerin was administered at a rate of 0.2–0.5 µg/kg/min until the liver lesions were removed. The characteristics of patients, surgery, intraoperative vital signs, blood loss, the condition of the surgical field, the dosage of norepinephrine, perioperative laboratory data, and postoperative complications were compared between groups. Blood loss during LH was considered the primary outcome.ResultsBlood loss during hepatectomy and total blood loss were significantly lower in the milrinone group compared with those in the nitroglycerin group (P < 0.05). Both the nitroglycerin group and milrinone group exerted similar CVP (P > 0.05). Nevertheless, the milrinone group had better surgical field grading during liver resection (P < 0.05) and also exhibited higher cardiac index and cardiac output during the surgery (P < 0.05). Significant differences were also found in terms of fluids administered during hepatectomy, urine volume during hepatectomy, total urine volume, and norepinephrine dosage used in the surgery between the two groups. The two groups showed a similar incidence of postoperative complications (P > 0.05).ConclusionOur findings indicate that the intraoperative infusion of milrinone can help in maintaining an LCVP and hemodynamic stability during LH while reducing intraoperative blood loss and providing a better surgical field compared with nitroglycerin.Trial registrationChiCTR2200056891,first registered on 22/02/2022.

A retrospective observational study evaluating the association between vasoactive–inotropic score and mortality after major abdominal surgery

The relationship between VISmax and mortality in patients undergoing major abdominal surgery remains unclear. This study aims to evaluate the association between VISmax and both short-term and long-term all-cause mortality in patients undergoing major abdominal surgery, VISmax was calculated (VISmax = dopamine dose [µg/kg/min] + dobutamine dose [µg/kg/min] + 100 × epinephrine dose [µg/kg/min] + 10 × milrinone dose [µg/kg/min] + 10,000 × vasopressin dose [units/kg/min] + 100 × norepinephrine dose [µg/kg/min]) using the maximum dosing rates of vasoactives and inotropics within the first 24 h postoperative ICU admission. The study included 512 patients first admitted to the intensive care unit (ICU) who were administered vasoactive drugs after major abdominal surgery. The data was extracted from the medical information mart in intensive care-IV database. VISmax was stratified into five categories: 0–5, > 5–15, > 15–30, > 30–45, and > 45. Compared to patients with the lowest VISmax (≤ 5), those with the high VISmax (> 45) had an increased risk of 30-day mortality (hazard ratio [HR] 3.73, 95% CI 1.16–12.02; P = 0.03) and 1-year mortality (HR 2.76, 95% CI 1.09–6.95; P = 0.03) in fully adjusted Cox models. The ROC analysis for VISmax predicting 30-day and 1-year mortality yielded AUC values of 0.69 (95% CI 0.64–0.75) and 0.67 (95% CI 0.62–0.72), respectively. In conclusion, elevated VISmax within the first postoperative 24 h after ICU admission was associated with increased risks of both short-term and long-term mortality in patients undergoing major abdominal surgery.