Doses Of Norepinephrine Research Articles

Extubation of patients with COVID-19 acute respiratory failure during extracorporeal membrane oxygenation support is associated with improved survival

Aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or COVID-19, infection resulting in acute respiratory distress syndrome (ARDS) requiring veno-venous or veno-arterial extracorporeal membrane oxygenation (VV or VA-ECMO) support is a life-threatening disease process that requires prolonged intubation and has a high risk of mortality. Methods: In this retrospective, observational, single-center cohort study, we attempt to better understand the role of extubation in the course of treatment by dichotomizing groups into those extubated early while remaining on ECMO treatment (group A), compared to patients who remained intubated for the entirety of their ECMO treatment (group B). Results: The data indicate that early extubation of patients with COVID-19-associated ARDS requiring ECMO support leads to improved survival rates for group A (93%) compared to prolonged intubation (group B) throughout the course of ECMO therapy (64%) (p = 0.13). Additionally, patients extubated earlier (19 days vs. 59 days; p = 0.012) required significantly fewer vasoactive drugs (norepinephrine dosing: 0.03 mcg/kg/min vs. 0.093 mcg/kg/min; p = 0.04), and were less likely to require a tracheostomy (0 vs. 4, p = 0.026). Conclusions: Although the utility of ECMO in severe ARDS patients remains a contentious topic, early extubation seems to increase survival rates and overall patient outcomes in patients with COVID-19-associated ARDS requiring ECMO support.

The mystery of methylene blue and its role in managing post-cardiac surgery vasoplegic shock

Background Vasoplegic syndrome is associated with high mortality. Methylene blue (MB) is a guanylate cyclase inhibitor that ameliorates this re-distributive type of shock. This study aims to investigate the outcome in patients who received MB early postoperatively. Methods 2753 patients who underwent cardiac surgery utilizing cardiopulmonary bypass at our institution in a time interval of two years were identified. The incidence of vasoplegic syndrome was 7.2% (n = 200). Pharmacy records identified 84 patients (group 1, MB group) who received methylene blue and 116 patients (group 2, Control group) who didn’t receive the drug. This single-center retrospective cohort study’s primary outcome was in-hospital mortality. Secondary outcomes were postoperative hemodialysis, serum lactate levels at 24 h postoperatively, and intensive care unit stay length in days. Results MB patients have a shorter ICU stay as compared to the control group (9 ± 8 days vs. 16 ± 6.9; p-value <.001). In the control group, postoperative hemodialysis was higher (20% in the MB group and 40% in the control group; p-value <.05). At 24 h post-op, the methylene blue group had reduced serum lactate levels (1.8 ± 1.2 vs. 4 ± 1.8 in the control group; p-value <.001). The methylene blue group had a decreased 24-hour norepinephrine dose (1.5 ± 1.2 vs. 2.8 ± 2 in the control group; p-value <.05). In-hospital mortality was not significantly different between the two groups (38% in the MB group vs. 43% in the control group). Conclusion Early postoperative administration of methylene blue in patients with vasoplegic syndrome shortens intensive care unit stay and contributes to less end-organ damage.

Up-and-down determination of prophylactic norepinephrine boluses combined with crystalloid co-load for preventing post-spinal anesthesia hypotension during cesarean section

BackgroundThe use of a fluid co-load has been shown to enhance hemodynamic stability and diminish the occurrence of hypotension after spinal anesthesia when paired with prophylactic norepinephrine. This research aimed to identify the effective dosages (ED90 and ED50) of prophylactic norepinephrine boluses, in conjunction with a crystalloid co-load, for the prevention of hypotension after spinal anesthesia in cesarean delivery patients.MethodsPatients were administered crystalloid co-loads at a dosage of 10 mL/kg, in addition to preventive norepinephrine dosages direct following spinal anesthesia administration. The dosages of norepinephrine were established employing the up-and-down sequential allocation technique, starting with 8 µg and progressively rising by 1 µg increments. The primary objective was to detect the effective dosage (ED90 and ED50) of norepinephrine necessary to avoid hypotension following spinal anesthesia.ResultsThe ED90 for a single norepinephrine bolus, in combination with a crystalloid co-load, was calculated to be 5.35 µg (95% CI: 4.75 to 7.13). The ED50 was determined to be 4.05 µg (95% CI: 3.68 to 4.46) using the up-and-down method and 3.926 µg (95% CI: 3.362 to 4.422) through the probit regression model.ConclusionA prophylactic norepinephrine bolus of 5.35 µg, administered with a crystalloid co-load, effectively prevents hypotension following the spinal anesthesia in cesarean delivery patients.

Comparison of the efficacy and safety of Landiolol and Esmolol in critically ill patients: a propensity score-matched study

BackgroundExcessive tachycardia is associated with impaired hemodynamics and worse outcome in critically ill patients. Previous studies suggested beneficial effect of β-blockers administration in ICU patients, including those with septic shock. However, comparisons in ICU settings are lacking. Our study aims to compare Landiolol and Esmolol regarding heart rate control and hemodynamic variables in general ICU patients.MethodsThis retrospective, observational study was conducted in a 56-bed ICU at a university hospital. A propensity score matching (PSM) was employed to balance baseline differences. Generalized estimating equations (GEE) were used to compare heart rate between two drugs. The primary outcome was heart rate control, while secondary outcomes included hemodynamic response, hospital length of stay (HLOS) and ICU length of stay (ICULOS).ResultsFrom June 2016 to December 2022, 438 patients were included after PSM, (292 in the Esmolol group and 146 the in Landiolol group). Baseline heart rate was similar between groups (Landiolol:120.0 [110.2, 131.0] bpm vs. Esmolol:120.0 [111.0, 129.0] bpm, p = 0.925). During 72 h. of β-blocker infusion, Landiolol reduced heart rate by 4.7 (1.3, 8.1) bpm, more than Esmolol (p = 0.007), while preserving a comparable proportion of patients able to stabilize vasopressor doses within the first 24 h. (82.9 vs. 80.8%, respectively, p = 0.596). Norepinephrine doses and lactate levels were similar between groups over 72 h., while the Landiolol group exhibited notably higher minimal ScvO2 levels (72% [63%, 78%] vs 68% [55%, 73%], respectively, p = 0.006) and a lower maximal PCO2 gap compared to the Esmolol group (7.0 [6.0, 9.0] vs. 8.0 [6.0, 10.0] mmHg, respectively, p = 0.040). Patients in the Landiolol group were observed to experience shorter HLOS than patients in the Esmolol group (26.5 [13.0, 42.0] vs 30.0 [17.0, 47.2] days, respectively, p = 0.044) and ICULOS (4.9 [2.8, 10.0] vs.6.7 [3.4, 13.1] days, respectively, p = 0.011).ConclusionLandiolol provides superior heart rate control in critically ill patients with tachycardia compared to Esmolol, without increasing vasopressor requirements during the first 24 h. Findings from ScvO2 levels and PCO2 gap suggest that Landiolol may exert less impact on cardiac output than Esmolol. Further studies, incorporating comprehensive hemodynamic monitoring, are warranted to clarify the clinical implications of heart rate control with β-blockers in ICU patients with tachycardia.

Effect on Neonatal Acid–Base Status of Phenylephrine and Norepinephrine Boluses for Management of Spinal Anesthesia-Induced Hypotension in Patients with Preeclampsia Undergoing Cesarean Delivery: A Randomized, Double-Blinded Trial

Purpose: Phenylephrine (PE) is the vasopressor of choice for spinal induced hypotension. In recent studies, norepinephrine (NE) has been used to manage hypotension following spinal anesthesia. However, its effect on neonatal acid–base status in preeclamptic mothers has not been well established. The aim of this study is to compare the neonatal acid–base outcomes of bolus doses of PE versus NE for the prevention of spinal anesthesia-induced hypotension in nonlaboring preeclamptic patients undergoing cesarean section. Methods: A randomized, double-blind study was conducted on 50 nonlaboring patients diagnosed with preeclampsia posted for cesarean section under spinal anesthesia. Patients were randomized to receive bolus doses of either PE or NE following hypotension. Neonatal umbilical artery blood gas analysis and maternal hemodynamics were compared. All the statistical tests were two sided and performed at a significance level of 0.05. Results: The study did not reveal any difference in the primary outcome of umbilical artery pH when using PE or NE in patients with preeclampsia (P 0.90). The secondary outcomes were also comparable. Conclusion: Our study shows that PE and NE are comparable in terms of fetal umbilical artery blood pH in nonlaboring preeclamptic patients undergoing cesarean section under spinal anesthesia.

Impact of Norepinephrine Use on Free Flap Survival in Breast Reconstructive Microsurgery.

The optimal method for maintaining intraoperative blood pressure during microsurgical procedures remains controversial. While intravenous fluid administration is essential, overfilling can lead to complications. Vasopressor agents are used cautiously due to their vasoconstrictive effects, which could potentially lead to flap failure. Numerous studies have explored the possible link between amine administration and free flap failure, yielding inconsistent results. This study aims to determine whether intraoperative norepinephrine administration increases the flap failure rate in microsurgical breast reconstructions. All women (n = 335) who underwent breast reconstruction using DIEP or PAP flaps (n = 400) in 2018 and 2022 in the Plastic Surgery Department of Georges-Pompidou European Hospital (Paris, France) were included in the study. These patients were classified into two groups based on the intraoperative administration of norepinephrine: the N+ group (50 patients) and the N- group (285 patients). Norepinephrine was administered when systolic blood pressure fell below 90 mmHg or mean arterial pressure (MAP) dropped below 65 mmHg, following fluid resuscitation in 2018, or without prior fluid loading in 2022. The primary endpoint was total flap loss. Secondary endpoints included arterial and venous thrombosis and the need for revision surgeries. Norepinephrine administration significantly increased the risk of total flap loss in DIEP and PAP flap surgeries (p < 0.001). It also heightened the risk of arterial thrombosis (p = 0.002) and venous thrombosis (p = 0.04), and led to a greater number of revision surgeries (p < 0.001). Subgroup analysis indicated that PAP flaps are more sensitive to norepinephrine compared to DIEP flaps. Our study suggests that the intraoperative administration of any dose of norepinephrine is associated with an increased risk of flap failure in breast reconstructive microsurgery using DIEP and PAP flaps.

Does Continuous Renal Replacement Therapy with oXiris in Septic Shock Have Any Positive Impact? Single-Centre Experience with oXiris Therapy in Septic Shock Patients

Background: Renal replacement therapy with an oXiris hemofilter may be helpful for patients with acute kidney injury in conjunction with sepsis and septic shock. The aim of this study was to assess the impact of an oXiris membrane on septic shock patients. Methods: All renal replacement therapies with oXiris (Baxter, Deerfield, IL, USA) performed between January 2018 and August 2021 were retrospectively analyzed. CRRT was initiated in continuous venovenous hemodiafiltration (CVVHDF) mode using Prismaflex System (Baxter). Demographic data, starting point of infection, source control, etiology, and course of treatment were analyzed. Results: A total of 32 patients were included in the study. Most patients treated with oXiris had acute kidney injury (AKI) and required CRRT. One patient had KDIGO 1 AKI (3.1%), three patients (9.4%) had KDIGO 2 AKI, and 28 patients (87.5%) had KDIGO 3 AKI. A statistically significant decrease in vasopressin dosage was required to achieve adequate MAP after 24 and 72 h, and a statistically significant decrease in norepinephrine dosage after 72 h was observed, with no SOFA score change on days 2 and 3. Procalcitonin and lactate levels did not change after 24 and 72 h. No beneficial effect on mortality was observed. Conclusions: Treatment with an oXiris membrane can positively impact vasopressors’ requirement but not influence SOFA score, procalcitonin or lactate levels, or mortality in septic shock patients.

The Effect of Dexmedetomidine on Inflammatory Factors and Clinical Outcomes in Patients With Septic Shock: A Randomized Clinical Trial

PurposeDexmedetomidine is a sedative-analgesic that is widely used in sepsis. However, its effect on septic shock remains unclear. This study aimed to investigate dexmedetomidine's effect on inflammatory biomarkers in septic shock. MethodsThe present study was a randomized controlled clinical trial. Patients with inclusion criteria were randomly allocated into either the dexmedetomidine (n = 24) or morphine + midazolam group (n = 24). The primary outcome was changes in inflammatory factors, including IL-1, IL-6, TNF-α, ESR, and CRP. The serum levels of inflammatory factors were measured at baseline and the end of the intervention. Secondary outcomes included the change in norepinephrine dose, vital signs, and SOFA scores. FindingsOf the 48 subjects, 52.08% were male. After intervention, IL-1, IL-6, and TNF-α levels significantly differed between the 2 groups (p = 0.011 and p < 0.001 and p < 0.001, respectively). Heart rate and systolic blood pressure decreased over time, but the two groups had no significant difference (p-value > 0.05). In addition, there was no significant difference in norepinephrine dose and SOFA score between the 2 groups (p-value > 0.05). ImplicationsSedation with dexmedetomidine can attenuate the inflammatory factors in septic shock. Also, dexmedetomidine did not worsen the hemodynamic parameters in septic shock patients.

Association between driving pressure, systemic inflammation and non-pulmonary organ dysfunction in patients with acute respiratory distress syndrome, a prospective pathophysiological study.

Driving pressure is thought to determine the effect of low tidal ventilation on survival in patients with acute respiratory distress syndrome. The leading cause of mortality in these patients is non-pulmonary multiorgan dysfunction, which is believed to worsen due to the biological response to mechanical ventilation (biotrauma). Therefore, we aimed to analyze the association between driving pressure, biotrauma, and non-pulmonary multiorgan dysfunction. Additionally, we analyzed this relationship for tidal volume/predicted body weight. Observational study that included adult patients with acute respiratory distress syndrome undergoing invasive mechanical ventilation admitted to the Hospital Clinic of Barcelona, Spain, between June 2019 and February 2021. We conducted mixed-effects models to assess the effects of driving pressure and tidal volume/predicted body weight on the evolution of 22 log-transformed biomarker variables during the first, third, and fifth days after study enrollment. These 22 systemic biomarkers characterized epithelial and endothelial pulmonary dysfunction, inflammation, and coagulation disorders in the included patients. In the same fashion, the association between driving pressure and non-pulmonary multiorgan dysfunction was evaluated by the non-pulmonary sequential organ failure assessment score (non-pulmonary SOFA) and its associated variables. Finally, we performed mediation analyses to assess whether the relationship between biomarkers and driving pressure was mediated by other ventilator-induced lung injury parameters. Thirty-eight patients were included. Driving pressure was independently associated with soluble Receptor for advanced glycation end-products, Interleukin (IL)-8, IL-6, IL-10, IL-17, Interferon-ɣ, Chemokine (C-C motif)-2, Vascular endothelial growth factor, Tissue factor, Protein C, Protein S, and higher dose of norepinephrine. However, this relationship attenuated over time. In contrast, tidal volume/predicted body weight was not associated with any of the 22 biomarkers tested . A concomitant increase in positive end-inspiratory plateau pressure or tidal volume did not mediate the effect of driving pressure on biomarkers. Conversely, the association between compliance of the respiratory system and pulmonary epithelial dysfunction was primarily mediated by driving pressure. Driving pressure, but not tidal volume/predicted body weight, was correlated with epithelial and endothelial pulmonary dysfunction, inflammation, coagulation disorders, and hemodynamic dysfunction. However, this relationship diminished over time.

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.

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&lt;0.001), serum procalcitonin (2.75±2.4 vs. 3.39±3.5, ng/ml; P&lt;0.001), serum CRP (90.2±57.4 vs. 175.6±100.9, mg/dl; P&lt;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&lt;0.001) and reduction in norepinephrine dose (6.47±2.7 vs.10.65±3.6, mcg/min; P&lt;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.

Donation After Circulatory Death Liver Transplantation: Impact of Normothermic Machine Perfusion on Key Variables.

During orthotopic liver transplantation, allograft reperfusion is a dynamic point in the operation and often requires vasoactive medications and blood transfusions. Normothermic machine perfusion (NMP) of liver allografts has emerged to increase the number of transplantable organs and may have utility during donation after circulatory death (DCD) liver transplantation in reducing transfusion burden and vasoactive medication requirements. This is a single-center retrospective study involving 226 DCD liver transplant recipients who received an allograft transported with NMP (DCD-NMP group) or with static cold storage (DCD-SCS group). Veno-venous bypass was not used in any patients. Infusion doses of norepinephrine, epinephrine, and vasopressin as well as bolus doses of vasoactive medications during reperfusion were recorded. Blood component therapy was recorded according to phase of liver transplantation and during the first 24 hours postprocedure. A total of 103 recipients in the DCD-NMP group and 123 patients in the DCD-SCS group were included. Post-reperfusion syndrome (PRS) incidence was reduced in the DCD-NMP group compared to the DCD-SCS group (10.7% [95% confidence interval, CI, 5.5%-18.3%] vs 42.3% [95% CI, 33.4%-51.5%]; P < .001). During the reperfusion period, patients in the DCD-SCS group required increased bolus doses of epinephrine and vasopressin compared to the DCD-NMP group (24.6 vs 7.5 µg; P < .001) and (5.4 vs 2.4 units; P < .001), respectively. The DCD-SCS group received a higher infusion dose of epinephrine during anhepatic phase, at reperfusion, and up to 90 minutes after reperfusion. In the postreperfusion period, there were significant increases in the transfusion of red blood cells (RBCs; 5.3 vs 3.7 units; P = .006), fresh frozen plasma (FFP; 3.4 vs 1.9 units; P < .001), cryoprecipitate (2.7 vs 1.8 pooled units; P = .015) and platelets (0.9 vs 0.4 units; P = .008) in the DCD-SCS group compared to the DCD-NMP group. During the first 24 hours postprocedure, transfusion of RBCs, FFP, and cryoprecipitate in the DCD-SCS group was increased compared to the DCD-NMP group ([2.6 vs 1.7 units; P = .028], [1.6 vs 0.8 units; P < .001], [1.5 vs 0.9 pooled units; P = .031]) respectively. Administration of tranexamic acid was more frequent in the DCD-SCS group during the post-reperfusion period compared to the DCD-NMP group (13% [95% CI, 5.7%-17.4%] vs 3.9% [95% CI, 1.1%-9.6% 95%]; P = .018). In DCD liver transplantation, use of NMP was associated with reduced incidence of PRS and decreased vasopressor and inotrope requirements at the time of allograft reperfusion compared to using SCS. Additionally, NMP was associated with reduced transfusion of all blood product components as well as antifibrinolytic agent administration in the post-reperfusion period. Reduced transfusion burden in the DCD-NMP group also occurred during the first 24 hours posttransplant.

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.