Administration Of Norepinephrine Research Articles

Norepinephrine versus phenylephrine for managing maternal hypotension during cesarean delivery under spinal anesthesia: a meta-analysis of maternal and neonatal outcomes

Norepinephrine or phenylephrine administration to prevent and treat hypotension during spinal anesthesia for cesarean section has been a significant topic of discussion. This meta-analysis aimed to update existing evidence and provide further insights into neonatal and maternal outcomes associated with norepinephrine and phenylephrine. Review of randomized controlled trials (RCTs) was performed to assess the effectiveness of norepinephrine and phenylephrine in managing maternal hypotension during cesarean delivery under spinal anesthesia. Neonatal umbilical cord blood pH and maternal hypotension were the primary outcomes. Based on the analysis of 26 RCTs with 2984 participants, we found no significant difference between the norepinephrine and phenylephrine groups in umbilical artery pH in neonates (mean difference (MD) 0.00; 95% confidence interval (CI) −0.00 to 0.01, p = 0.20). Neonates Apgar scores did not differ between both groups. Norepinephrine was associated with lower incidences of bradycardia (risk ratio (RR) 0.44; 95% CI 0.37 to 0.51, p < 0.001) and reactive hypertension (RR 0.53; 95% CI 0.39 to 0.72, p < 0.001) in parturient women than phenylephrine. In neither group did umbilical cord blood levels of partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2) and base excess (BE) levels of neonates differ significantly, nor did maternal hypotension, nausea or vomiting incidence during delivery. For maternal hypotension after spinal anesthesia, norepinephrine and phenylephrine did not significantly differ in neonatal acidemia. Despite similarities to phenylephrine in managing hypotension and maintaining maternal hemodynamic stability, norepinephrine is a promising alternative.

Early administration of norepinephrine in sepsis: Multicenter randomized clinical trial (EA-NE-S-TUN) study protocol.

One of the most important components of sepsis management is hemodynamic restoration. If the target mean arterial pressure (MAP) is not obtained, the first recommendation is for volume expansion, and the second is for norepinephrine (NE). We describe the methodology of a randomized multicenter trial aiming to assess the hypothesis that low-dose NE given early in adult patients with sepsis will provide better control of shock within 6 hours from therapy starting compared to standard care. This trial includes ICU septic patients in whom MAP decrease below 65 mmHg to be randomized into 2 groups: early NE-group versus standard care-group. The patient's attending clinician will determine how much volume expansion is necessary to meet the target of a MAP > 65 mm Hg. If this target not achieved, after at least 30 ml/kg and guided by the available indices of fluid responsiveness, NE will be used in a usual way. The latter must follow a consensual schedule elaborated by the investigating centers. Parameters to be taken at inclusion and at H6 are: lactates, cardiac ultrasound parameters (stroke volume (SV), cardiac output (CO), E/E' ratio), and P/F ratio. MAP and diuresis are recorded hourly. Our primary outcome is the shock control defined as a composite criterion (MAP > 65 mm Hg for 2 consecutive measurements and urinary output > 0.5 ml/kg/h for 2 consecutive hours) within 6 hours. Secondary outcomes: Decrease in serum lactate> 10% from baseline within 6 hours, the received fluid volume within 6 hours, variation of CO and E/E', and 28 days-Mortality. The study is ongoing and aims to include at least 100 patients per arm. This study is likely to contribute to support the indication of early initiation of NE with the aim to restrict fluid intake in septic patients. (ClinicalTrials.gov ID: NCT05836272).

Effect of Blood Pressure Augmentation on CVA Patients who are out of Injection TPA (Tissue Plasminogen Activator) and Mechanical Thrombectomy Window

Background: Ischemic stroke is a leading cause of morbidity and mortality worldwide, prompting an urgent need for effective treatments outside the standard therapeutic window. With an estimated 6.5 million stroke-related deaths annually and a particular prevalence in the 18-49 age demographic, there is a substantial burden on healthcare systems. Intravenous thrombolysis and mechanical thrombectomy are time-sensitive treatments that are not universally accessible, highlighting the need for alternative strategies. Objective: The study aimed to evaluate the efficacy of induced hypertension as a therapeutic intervention for ischemic stroke patients who are beyond the window for conventional reperfusion therapies. Methods: This cross-sectional observational study was conducted at the Hyper Acute Stroke Unit (HASU) of PEMH, Rawalpindi. Over four months, 50 male patients who had suffered an ischemic stroke and were outside the therapeutic window for TPA and mechanical thrombectomy were recruited. Induced hypertension was achieved through intravenous administration of norepinephrine, titrated to maintain systolic blood pressure between 180-200 mmHg. Blood pressure was recorded at baseline, immediately before norepinephrine administration, and every 12 hours thereafter. Muscle power was assessed using the Medical Research Council (MRC) scale at 24-hour intervals over a 3-day observational period. Results: The mean systolic blood pressure was 140±5.07 mmHg, and the mean diastolic blood pressure was 94.16±4.71 mmHg, with a mean patient age of 55±4.4 years. Following induced hypertension, 30 out of the 50 patients (60%) showed improvement in muscle power. Specifically, in Group 1 (6 patients with leg muscle weakness), 3 patients improved from an MRC scale of 2 to 3, and 1 patient improved from an MRC scale of 3 to 4. In Group 2 (15 patients with upper and lower limb weakness), 7 patients improved from an MRC scale of 2 to 3, and 4 patients improved from an MRC scale of 3 to 4. Similar improvements were observed in other groups, with overall improvements ranging from 37.5% to 80% within individual subgroups. Conclusion: Induced hypertension via norepinephrine infusion appears to be a promising therapeutic strategy to improve muscle power in ischemic stroke patients who cannot receive standard reperfusion treatments. This intervention could potentially bridge the treatment gap for patients who present outside of the traditional therapeutic time frame.

A model for predicting return of spontaneous circulation and neurological outcomes in adults after in-hospital cardiac arrest: development and evaluation.

In-hospital CA (IHCA) is associated with rates of high incidence, low return of spontaneous circulation (ROSC), low survival to discharge, and poor neurological outcomes. We aimed to construct and evaluate prediction models for non-return of spontaneous circulation (non-ROSC) and poor neurological outcomes 12 months after ROSC (PNO-12). We retrospectively analyzed baseline and clinical data from patients experiencing cardiac arrest (CA) in a big academic hospital of Jilin University in China. Patients experiencing CA between September 1, 2019 and December 31, 2020 were categorized into the ROSC and non-ROSC groups. Patients maintaining ROSC >20 min were divided into the good and PNO-12 subgroups. Univariate and multivariate logistic regression identified independent factors associated with non-ROSC and PNO-12. Two nomogram prediction models were constructed and evaluated. Of 2,129 patients with IHCA, 851 were included in the study. Multivariate logistic regression analysis revealed that male sex, age >80 years, CPR duration >23 min, and total dose of adrenaline >3 mg were significant risk factors for non-ROSC. Before CA, combined arrhythmia, initial defibrillation rhythm, and advanced airway management (mainly as endotracheal intubation) also influenced outcomes. The area under the receiver operating characteristic curve in the prediction model was 0.904 (C-index: 0.901). Respiratory failure, shock, CA in the monitoring area, advanced airway management, and noradrenaline administration were independent risk factors for PNO-12. The AUC was 0.912 (C-index: 0.918). Prediction models based on IHCA data could be helpful to reduce mortality rates and improve prognosis.

Abstract 317: Development of a Swine Model of Rapidly-Induced Septic Shock Using Single Lipopolysaccharide Infusion and Titratable Inhaled Nitric Oxide to Prevent Severe Pulmonary Vasoconstriction

Objective: A serious limitation of LPS-induced swine models of septic shock is severe pulmonary vasoconstriction triggered, in part, by the pulmonary release of thromboxane A2. Efforts to overcome this limitation have included a stepwise increase in LPS dosing, intravenous aspirin derivatives, and inhaled nitric oxide (NO). We studied the effects of titrated inhaled NO given coincident with rapid LPS-infusion aimed at inducing the key features of septic shock over a shorter time period. Methods: We developed a LabVIEW-controlled system for inhaled NO delivery and monitoring. Exploratory studies showed that an NO concentration of up to 300 ppm sufficed to prevent significant pulmonary vasoconstriction despite delivery of a full LPS dose (12.6 μg/kg) in 30 minutes. We used this approach in 6 male domestic pigs (39.2 - 41.1 kg) and assessed hemodynamic and metabolic effects over 6 hours. NO and LPS infusion were started concurrently. Fluid resuscitation and vasopressor therapy were guided by macrohemodynamic measurements using custom-developed LabVIEW-controlled closed-loop algorithms. Results: Shown are medians with IQ25 and IQ75. LPS infusion increased pulmonary vascular resistance from 112 [72, 127] at baseline to 213 [120, 313] dynes-sec/cm 5 after 20 minutes. NO (139 [131, 166] ml/min) rapidly blunted the effect preventing the mean pulmonary artery pressure from exceeding 30 mmHg, avoiding detrimental effects on right ventricular function throughout the experiment. NO was rapidly de-escalated over 30 minutes using a closed-loop algorithm developed to prevent the mean pulmonary artery pressure from exceeding 30 mmHg. Within 60 minutes of LPS infusion start, animals began to develop key features of septic shock including tachycardia, hypotension, and systemic vasodilation triggering fluid resuscitation and norepinephrine administration. Additionally, blood lactate increased from 1.06 [0.90, 1.45] at baseline to 4.14 [2.43, 8.78] mmol/l after 3 hours remaining stable for an additional hour and subsequently decreasing in 3 and increasing in the other 3 animals, with half of the animals surviving the 6-h period. Conclusion: We developed a swine model of rapidly-induced key features of septic shock useful to explore early septic shock management.

Modeling the relationship between arterial blood pressure and sublingual microcirculatory blood flow assessed by Sidestream Dark Field videomicroscopy: An experimental study in anesthetized piglets.

Microcirculation is frequently assessed using videomicroscopy in the sublingual mucosa. However, limited research has been conducted on the existence of blood flow autoregulation in this region. We conducted a study in an experimental porcine model of pharmacologically induced hypotension to evaluate the relationship between mean arterial pressure (MAP) and the microvascular flow index (MFI). We hypothesized that this relationship would be linear in the absence of autoregulation or bilinear if autoregulation is present. Seven pigs underwent blood pressure changes induced by norepinephrine (hypertension) and sevoflurane (hypotension) administration. Sublingual microcirculation was assessed using a sidestream dark field device, and videos were recorded at different MAP levels ranging from 30 to 110 mmHg. MFI was calculated using the quadrant-based method. For our first hypothesis, we constructed a linear mixed model, while a bilinear model was used for the second hypothesis. The linear model demonstrated a statistically significant association (P = 0.03) described by the equation: MFI = 2.29 + 0.004 x MAP. The bilinear model identified a statistically significant inflection point at MAP = 99 mmHg (P = 0.01) with MFI = 2.7 AU (P < 0.0001). For MAP <99 mmHg, the relationship was: MFI = 2.26 + 0.004 x MAP, and for MAP >99 mmHg, MFI = 2.7. Despite statistical significance, neither model provided a satisfactory graphical fit due to high inter- and intra-individual variability. Consequently, this study did not allow us to draw conclusions regarding the presence of blood autoregulation.

Intra-abdominal laparoscopic assessment of organs perfusion using imaging photoplethysmography.

An objective evaluation of the functional state and viability of biological tissues during minimally invasive surgery remains unsolved task. Various non-contact methods for evaluating perfusion during laparoscopic surgery are discussed in the literature, but so far there have been no reports of their use in clinical settings. Imaging photoplethysmography (iPPG) is a new method for quantitative assessment of perfusion distribution along the tissue. This is the first study in which we demonstrate successful use of iPPG to assess perfusion of organs during laparoscopic surgery in an operation theater. We used a standard rigid laparoscope connected to a standard digital monochrome camera, and abdominal organs were illuminated by green light. A distinctive feature is the synchronous recording of video frames and electrocardiogram with subsequent correlation data processing. During the laparoscopically assisted surgeries in nine cancer patients, the gradient of perfusion of the affected organs was evaluated. In particular, measurements were carried out before preparing a part of the intestine or stomach for resection, after anastomosis, or during physiological tests. The spatial distribution of perfusion and its changes over time were successfully measured in all surgical cases. In particular, perfusion gradient of an intestine before resection was visualized and quantified by our iPPG laparoscope in all respective cases. It was also demonstrated that systemic administration of norepinephrine leads to a sharper gradient between well and poorly perfused areas of the colon. In four surgical cases, we have shown capability of the laparoscopic iPPG system for intra-abdominal assessment of perfusion in the anastomosed organs. Moreover, good repeatability of continuous long-term measurements of tissue perfusion inside the abdominal cavity was experimentally demonstrated. Our study carried out in real clinical settings has shown that iPPG laparoscope is feasible for intra-abdominal visualization and quantitative assessment of perfusion distribution.

A Randomized, Double-Blind, Graded Dose-Response Study of Norepinephrine Administration for Prevention of Post-Spinal Hypotension during Elective Cesarean Delivery.

Norepinephrine has been recently introduced for prophylaxis against post-spinal hypotension during cesarean delivery; however, no data are available regarding its optimum dosing scheme. The primary objective of this study is to compare three different infusion and bolus dose combinations of norepinephrine for prophylaxis against post-spinal hypotension during cesarean delivery. This randomized, double-blind study was performed between February 2021 and May 2022. The study protocol was registered at Clinicaltrials.gov with the identification number NCT04701190. A total of 192 parturients were enrolled into this study. Patients were assigned to three groups-Zero-Bolus High-Infusion (Group ZBHI, 0 µg/0.1 µg kg-1 min-1, n = 61), Moderate-Bolus Moderate-Infusion (Group MBMI, 5 µg/0.075 µg kg-1 min-1, n = 61) and High-Bolus Low-Infusion (Group HBLI, 10 µg/0.05 µg kg-1 min-1, n = 61)-according to different combinations of norepinephrine infusion and bolus doses. All patients received spinal anesthesia with 10 mg hyperbaric bupivacaine plus 12.5 µg fentanyl. Immediately after cerebrospinal fluid was obtained, patients underwent a norepinephrine protocol corresponding to the randomized group. The primary outcome was the incidence of post-spinal hypotension. Secondary outcomes were post-delivery hypotension, frequency of post-spinal hypertension and bradycardia, and neonatal outcomes. The incidence of post-spinal hypotension was 11.7% in Group HBLI, 6.7% in Group ZBHI and 1.7% in Group MBMI (p = 0.1). The overall incidence of post-delivery hypotension in parturients was 41.1% (p = 0.797). The lowest frequency of post-spinal bradycardia (8.3%) and hypertension (11.7%) was seen in Group HBLI. The neonatal APGAR scores at 1st minute were higher in Group MBMI than in Group ZBHI (8.58 vs. 8.23, p = 0.001). All three infusion and bolus dose combinations of norepinephrine effectively reduced the incidence of post-spinal hypotension. However, high-dose bolus (10 µg) followed by low-dose infusion (0.05 µg kg-1 min-1) of norepinephrine can be preferred due to the reduced frequency of bradycardia and hypertension during cesarean delivery under spinal anesthesia.

Successful use of extracorporeal membrane oxygenation for life‐threatening macrophage activation syndrome after treatment with tocilizumab in an systemic juvenile idiopathic arthritis patient

AbstractMacrophage activation syndrome (MAS) is a rare, potentially life‐threatening condition in rheumatic diseases. The primary treatments consist of high‐dose corticosteroids and immunosuppressive drugs, although more recently, cytokine inhibitors like anakinra or tocilizumab (TCZ) have been reported. We present a case of a child with systemic juvenile idiopathic arthritis (sJIA). After receiving a single infusion of TCZ, the child developed progressive hypoxia and was subsequently transferred to the pediatric intensive care unit (PICU) after 4 days. An immediate postintubation chest X‐ray revealed a diffuse exudative lesion. Despite continuous efforts to provide mechanical ventilation and respiratory support, the patient's oxygen saturation continued to decline. Moreover, the patient developed hemodynamic compromise, necessitating the administration of norepinephrine. Eventually, vasopressin and dopamine were added to maintain stable hemodynamics. After an intensive but ineffective treatment, extracorporeal membrane oxygenation (ECMO) was initiated in the PICU after 16 h. The patient successfully recovered and was weaned off ECMO support after 60 h. Following discharge from the PICU, given the severe refractory clinical features, we made an attempt to readminister TCZ treatment. However, within half an hour of TCZ infusion, the patient experienced anaphylaxis characterized by palpitations and chest tightness, leading to the discontinuation of TCZ. TCZ, as a biological agent, is commonly used in the treatment of sJIA. Nonetheless, the occurrence of MAS and anaphylaxis following TCZ administration for sJIA may be more prevalent than previously recognized. Pediatric rheumatologists should exercise caution when initiating TCZ for active sJIA. Furthermore, we want to underscore the importance of life‐saving techniques such as ECMO for sJIA patients in emergency situations.

Performance of closed-loop systems for intravenous drug administration: a systematic review and meta-analysis of randomised controlled trials.

Closed-loop drug delivery systems are autonomous computers able to administer medication in response to changes in physiological parameters (controlled variables). While limited evidence suggested that closed-loop systems can perform better than manual drug administration in certain settings, this technology remains a research tool with an uncertain risk/benefit profile. Our aim was comparing the performance of closed-loop systems with manual intravenous drug administration in adults. We searched MEDLINE, CENTRAL, and Embase from inception until November 2022, without restriction to language. We assessed for inclusion randomised controlled trials comparing closed-loop and manual administration of intravenous drugs in adults, intraoperatively or in the Intensive Care Unit. We identified 32 studies on closed-loop administration of propofol, noradrenaline, phenylephrine, insulin, neuromuscular blockers, and vasodilators. Most studies were at moderate or high risk of bias. The results showed that closed-loop systems reduced the duration of blood pressure outside prespecified targets during noradrenaline (MD 14.9%, 95% CI 9.6-20.2%, I2 = 66.6%) and vasodilators administration (MD 7.4%, 95% CI 5.2-9.7%, I2 = 62.3%). Closed-loop systems also decreased the duration of recovery after propofol (MD 1.3min, 95% CI 0.4-2.1min, I2 = 58.6%) and neuromuscular blockers (MD 9.0min, 95% CI 7.9-10.0min, I2 = 0%). The certainty of the evidence was low or very low for most outcomes. Automatic technology may be used to improve the hemodynamic profile during noradrenaline and vasodilators administration and reduce the duration of postanaesthetic recovery.Registration: This systematic review was registered with PROSPERO (CRD42022336950) on the 7th of June 2022.

Should we initiate vasopressors earlier in patients with septic shock: A mini systemic review.

Septic shock treatment remains a major challenge for intensive care units, despite the recent prominent advances in both management and outcomes. Vasopressors serve as a cornerstone of septic shock therapy, but there is still controversy over the timing of administration. Specifically, it remains unclear whether vasopressors should be used early in the course of treatment. Here, we provide a systematic review of the literature on the timing of vasopressor administration. Research was systematically identified through PubMed, Embase and Cochrane searching according to PRISMA guidelines. Fourteen studies met the eligibility criteria and were included in the review. The pathophysiological basis for early vasopressor use was classified, with the exploration on indications for the early administration of mono-vasopressors or their combination with vasopressin or angiotensinII. We found that mortality was 28.1%-47.7% in the early vasopressors group, and 33.6%-54.5% in the control group. We also investigated the issue of vasopressor responsiveness. Furthermore, we acknowledged the subsequent challenge of administration of high-dose norepinephrine via peripheral veins with early vasopressor use. Based on the literature review, we propose a possible protocol for the early initiation of vasopressors in septic shock resuscitation.

A case report of spontaneous pectoral hematoma in a male with background antiplatelet therapy after severe COVID-19 infection

BackgroundSpontaneous muscle hematoma is a rare complication in hospitalized patients with COVID-19. We present a case of spontaneous pectoral hematoma occurring after COVID-19 infection and anticoagulation therapy.Case presentationA 69-year-old male presented to the hospital with a two-week history of shortness of breath and a one-week history of high fever. Despite testing positive for COVID-19, the patient’s symptoms did not improve with two doses of ritonavir-boosted nirmatrelvir (Paxlovid). A chest CT scan revealed pulmonary infection and SpO2 tested between 80% and 85% at rest in local hospital. The patient transferred to our intensive care unit, then received multiple treatments, including high flow nasal oxygen (HFNO), antibiotics, methylprednisolone, IL-6 receptor antagonist monoclonal antibody (tocilizumab), and an increased D-Dimer level leaded to intermediate dose of anticoagulation therapy. However, on the 10th day of hospitalization, the patient developed a hematoma in the left pectoralis major muscle. This was accompanied by hemorrhagic shock, necessitating the administration of norepinephrine, fluid resuscitation, and a blood transfusion. Arterial embolization was performed to manage the bleeding, resulting in stabilization of the patient’s condition. Following discharge, the patient experienced an uneventful recovery over a period of six months.ConclusionsSevere COVID-19 patients undergoing routine therapeutic anticoagulation may experience fatal bleeding complications. The ideal dosage of anticoagulants for these patients remains uncertain, especially in the patient with a background of anticoagulation or dual antiplatelet therapy. We present a case of spontaneous muscle hematoma accompanied by hemorrhagic shock. The notable reduction in hemoglobin levels indicated significant bleeding, which was confirmed through contrast angiography and cured by arterial embolization. This case underscores the importance of additional research to determine the appropriate utilization of therapeutic anticoagulation in severe COVID-19 patients already undergoing antithrombotic therapy.

Prehospital Administration of Norepinephrine and Epinephrine for Shock after Resuscitation from Cardiac Arrest

Introduction Shock after resuscitation from out-of-hospital cardiac arrest (OHCA) is often treated with vasopressors. We examined whether infusion of epinephrine versus norepinephrine was associated with prehospital rearrest and neurologically favorable survival among OHCA patients. Methods This retrospective study included OHCA cases in Seattle, Washington from 2014-2021 who had return of spontaneous circulation (ROSC) followed by vasopressor infusion. Our primary exposure was infusion of epinephrine or norepinephrine. Our primary outcome was prehospital rearrest. Secondary outcomes included survival and neurologically favorable outcome (Cerebral Performance Category score of 1 or 2). We used multivariable logistic regression to test associations between exposures and outcomes adjusting for key covariates. Results Of 451 OHCA patients with ROSC followed by vasopressor infusion, 253 (56%) received norepinephrine and 198 (44%) received epinephrine infusions. Those who received epinephrine were older (median 66 [interquartile ranges {IQR} 53-79] vs 63 [IQR 47-75] years), but otherwise had similar baseline characteristics. Patients who received epinephrine were twice as likely to rearrest (55% vs 25%). After adjustment, the difference in rearrest rates between epinephrine and norepinephrine persisted (OR 3.28, 95%CI 2.25-5.08), and the odds of pulses at hospital arrival were lower in the epinephrine group (OR 0.52 95%CI 0.32-0.83). After adjustment, there was no difference in neurologically favorable survival, survival to hospital admission, or survival to discharge. Conclusion Patients who received epinephrine infusions after ROSC suffered prehospital rearrest more frequently than those who received norepinephrine. Survival and neurological status at hospital discharge were similar. Future trials should examine the optimal approach to hemodynamic management for post-OHCA shock.

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.

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.

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.

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.