Doses Of Norepinephrine Research Articles

Serum Sestrin2 Was Lower in Septic Shock Patients with Cardiomyopathy.

Background To determine the clinical significance of variations in serum sestrin2 protein levels in the development of septic cardiomyopathy in septic shock patients. Methods The serum sestrin2 concentrations of each sample were determined using ELISA in a total of 67 control persons and 188 patients with septic shock. Furthermore, using transthoracic echocardiography, septic shock patients were split into two groups based on whether or not cardiomyopathy had developed, and the differences in each index between the two groups were analyzed. We looked at the relationship between serum sestrin2 levels, norepinephrine dosage, and NTproBNP levels. The influencing variables for the prediction of septic cardiomyopathy linked with the development of septic cardiomyopathy and clinical prognosis in septic cardiomyopathy were determined using multivariate binary logistic regression. Results Assessment of left ventricular systolic function by measurement of LVEF revealed that 61/188 (32.4%) of the 188 patients with septic shock included in the research satisfied the diagnostic criteria for septic cardiomyopathy. (1) Sestrin2 protein levels showed a significant difference between septic shock and healthy controls (p < 0.01). (2) Compared to the group without septic cardiomyopathy, the group with combined septic cardiomyopathy had lower serum sestrin2 protein levels (p < 0.05), lower systolic blood pressure (p < 0.05), and higher plasma NTproBNP levels (p < 0.01) and used greater norepinephrine dosages (p < 0.01). The levels of serum sestrin2 protein revealed a little negative relationship with NTproBNP and norepinephrine dose. However, a binary logistic regression analysis revealed that none of these factors was an independent predictor of septic shock. (3) Age, lactate level, SOFA score, positive bacteremia, and sestrin2 protein were shown to be substantial discrepancies in clinical outcomes in patients with septic cardiomyopathy, becoming variables that impact clinical outcomes. Positive bacteremia (p = 0.031, OR = 5.084), SOFA score (p = 0.021, OR = 1.304), and sestrin2 protein (p = 0.039, OR = 0.897) were revealed to have independent influences in predicting clinical mortality outcome in septic cardiomyopathy using multivariate binary logistic regression. Conclusion High serum sestrin2 levels clearly distinguish septic shock patients from healthy controls, whereas low serum sestrin2 levels are related with cardiac dysfunction to some extent but are not an independent influence factor for septic cardiomyopathy. Low serum sestrin2 levels were shown to be useful in predicting clinical outcome in patients with septic cardiomyopathy.

Decreased renal cortical perfusion, independent of changes in renal blood flow and sublingual microcirculatory impairment, is associated with the severity of acute kidney injury in patients with septic shock

BackgroundReduced renal perfusion has been implicated in the development of septic AKI. However, the relative contributions of macro- and microcirculatory blood flow and the extent to which impaired perfusion is an intrinsic renal phenomenon or part of a wider systemic shock state remains unclear.MethodsSingle-centre prospective longitudinal observational study was carried out. Assessments were made at Day 0, 1, 2 and 4 after ICU admission of renal cortical perfusion in 50 patients with septic shock and ten healthy volunteers using contrast-enhanced ultrasound (CEUS). Contemporaneous measurements were made using transthoracic echocardiography of cardiac output. Renal artery blood flow was calculated using velocity time integral and vessel diameter. Assessment of the sublingual microcirculation was made using handheld video microscopy. Patients were classified based on the degree of AKI: severe = KDIGO 3 v non-severe = KDIGO 0–2.ResultsAt study enrolment, patients with severe AKI (37/50) had prolonged CEUS mean transit time (mTT) (10.2 vs. 5.5 s, p < 0.05), and reduced wash-in rate (WiR) (409 vs. 1203 au, p < 0.05) and perfusion index (PI) (485 vs. 1758 au, p < 0.05); differences persisted throughout the entire study. Conversely, there were no differences in either cardiac index, renal blood flow or renal resistive index. Sublingual microcirculatory variables were not significantly different between groups at study enrolment or at any subsequent time point. Although lactate was higher in the severe AKI group at study enrolment, these differences did not persist, and there were no differences in either ScvO2 or ScvCO2-SaCO2 between groups. Patients with severe AKI received higher doses of noradrenaline (0.34 vs. 0.21mcg/kg/min, p < 0.05). Linear regression analysis showed no correlation between mTT and cardiac index (R-0.18) or microcirculatory flow index (R-0.16).ConclusionRenal cortical hypoperfusion is a persistent feature in critically ill septic patients who develop AKI and does not appear to be caused by reductions in macrovascular renal blood flow or cardiac output. Cortical hypoperfusion appears not be associated with changes in the sublingual microcirculation, raising the possibility of a specific renal pathogenesis that may be amenable to therapeutic intervention.Trial Registration Clinical Trials.gov NCT03713307, 19 Oct 2018.

Applicability of Vasopressor Trials in Adult Critical Care: A Prospective Multicentre Meta-Epidemiologic Cohort Study.

ObjectiveTo assess the applicability of evidence from landmark randomized controlled trials (RCTs) of vasopressor treatment in critically ill adults.Study Design and SettingThis prospective, multi-center cohort study was conducted at five medical and surgical intensive care units at three tertiary care centers. Consecutive cases of newly initiated vasopressor treatment were included. The primary end point was the proportion of patients (≥18 years) who met the eligibility criteria of 25 RCTs of vasopressor therapy in critically ill adults included in the most recent Cochrane review. Multilevel Poisson regression was used to estimate the eligibility proportions with 95% confidence intervals for each trial. Secondary end points included the eligibility criteria that contributed most to trial ineligibility, and the relationship between eligibility proportions and (i) the Pragmatic-Explanatory Continuum Indicator Summary-2 (PRECIS-2) score, and (ii) the recruitment-to-screening ratio of each RCT. The PRECIS-2 score was used to assess the degree of pragmatism of each trial.ResultsBetween January 1, 2017, and January 1, 2019, a total of 1189 cases of newly initiated vasopressor therapy were included. The median proportion of cases meeting eligibility criteria for all 25 RCTs ranged from 1.3% to 6.0%. The eligibility criteria contributing most to trial ineligibility were the exceedance of a specific norepinephrine dose, the presence of a particular shock type, and the drop below a particular blood pressure value. Eligibility proportions increased with the PRECIS-2 score but not with the recruitment-to-screening ratio of the trials.ConclusionThe applicability of evidence from available trials on vasopressor treatment in critically ill adults to patients receiving vasopressors in daily practice is limited. Applicability increases with the degree of study pragmatism but is not reflected in a high recruitment-to-screening ratio. Our findings may help researchers design vasopressor trials and promote standardized assessment and reporting of the degree of pragmatism achieved.

Prognostic value of soluble endoglin in patients with septic shock and severe COVID-19.

Sepsis is a clinical syndrome characterized by a dysregulated response to infection. It represents a leading cause of mortality in ICU patients worldwide. Although sepsis is in the point of interest of research for several decades, its clinical management and patient survival are improving slowly. Monitoring of the biomarkers and their combinations could help in early diagnosis, estimation of prognosis and patient's stratification and response to the treatment. Circulating soluble endoglin (sEng) is the cleaved extracellular part of transmembrane glycoprotein endoglin. As a biomarker, sEng has been tested in several pathologic conditions where its elevation was associated with endothelial dysfunction. In this study we have tested the ability of sEng to predict mortality and its correlation with other clinical characteristics in the cohort of septic shock patients (n = 37) and patients with severe COVID-19 (n = 40). In patients with COVID-19 sEng did not predict mortality or correlate with markers of organ dysfunction. In contrast, in septic shock the level of sEng was significantly higher in patients with early mortality (p = 0.019; AUC = 0.801). Moreover, sEng levels correlated with signs of circulatory failure (required dose of noradrenalin and lactate levels; p = 0.002 and 0.016, respectively). The predominant clinical problem in patients with COVID-19 was ARDS, and although they often showed signs of other organ dysfunction, circulatory failure was exceptional. This potentially explains the difference between sEng levels in COVID-19 and septic shock. In conclusion, we have confirmed that sEng may reflect the extent of the circulatory failure in septic shock patients and thus could be potentially used for the early identification of patients with the highest degree of endothelial dysfunction who would benefit from endothelium-targeted individualized therapy.

Timing of Vasopressin Addition to Norepinephrine and Efficacy Outcomes in Patients With Septic Shock.

Current guidelines recommend norepinephrine as the first-line vasopressor in septic shock followed by addition of vasopressin to achieve a goal mean arterial pressure. Limited evidence exists evaluating how the timing of vasopressin addition affects clinical outcomes in septic shock. The objective of this study was to determine whether the timing of the addition of vasopressin to norepinephrine affects shock resolution. This was a multi-site, single system, retrospective cohort, institutional review board (IRB)-approved study examining adult patients with septic shock who received norepinephrine and vasopressin. Patients were divided and statistically analyzed in two subgroups: early vasopressin addition (<3 hours) and late vasopressin addition (≥3 hours). The primary outcome was time to shock resolution, defined as vasopressor free for at least 24 hours. Secondary outcomes included norepinephrine dose at 3 hours after initiation of vasopressin, in-hospital mortality, and intensive care unit length of stay. A total of 243 patients were included in this study. A statistically significant decrease in time to shock resolution was observed in the early vasopressin addition group compared to the late vasopressin addition group (37.6 hours vs 60.7 hours; adjusted hazard ratio [HR]: 2.07 [1.48-2.89; P = <0.001]). The early addition of vasopressin did not affect norepinephrine dose or in-hospital mortality but did lead to a decreased intensive care unit (ICU) length of stay (4.3 days vs 5.3 days, P = 0.02). Addition of vasopressin to norepinephrine within 3 hours was associated with a faster time to shock resolution. These findings suggest a potential for improved clinical outcomes with earlier vasopressin addition.

A Randomized Double-blind Comparison of Phenylephrine and Norepinephrine for the Management of Postspinal Hypotension in Pre-eclamptic Patients Undergoing Cesarean Section

(Eur J Anaesthesiol. 2021;38:1077–1084) Phenylephrine is the vasopressor of choice during cesarean delivery (CD) with spinal anesthesia; however, it can cause reflex bradycardia. Norepinephrine is being investigated as an alternative due to its ability to maintain better blood pressure (BP), heart rate, and cardiac output compared with phenylephrine while still seeing similar neonatal outcomes. Studies involving pre-eclamptic women need to be conducted to determine norepinephrine’s effectiveness in this population. This study aimed to compare bolus doses of norepinephrine and phenylephrine for postspinal hypotension in pre-eclamptic women undergoing CD.

The Association of Norepinephrine Utilization With Mortality Risk in Trauma Patients

IntroductionWhile the pillars of trauma resuscitation are surgical hemostasis and blood product administration, norepinephrine (NE) can be used as an adjunct. The goal of this study was to evaluate the relationship between the maximum dose of NE, timing of NE administration, and mortality in trauma patients. MethodsPatients admitted between January 2013 and January 2021 treated with NE were reviewed. Univariate and multivariate logistic regression were used to assess whether maximum NE dose was independently associated with mortality. Optimal dosage rates for NE were determined via Youden Index. Subgroup analyses comparing those who received NE within versus after the first 24 h of admission were conducted. ResultsThree hundred fifty-first trauma patients were included, with 217 (62%) surviving. Patients who died received an average maximum dose of 16.7 mcg/min compared to 9.1 mcg/min in survivors (P = 0.0003). Mortality rate increased with dosage (P < 0.0001), with doses greater than 20 mcg/min having 79% mortality. Those who received NE within the first 24 h had an inflection point in mortality at 16 mcg/min (Youden = 0.45) (OR 1.06; 95% CI 1.03-1.10). For patients who received NE after the first 24 h, an inflection point in mortality was at 10 mcg/min (Youden = 0.34) (OR 1.09; 95% CI 1.04-1.14). ConclusionsHigher maximum doses of NE were associated with increased mortality. Patients initiated on NE more than 24 h into their admission displayed an inflection point at a lower dose than those initiated later. This suggests that trauma patients initiated on NE after 24 h from injury may have a dire prognosis.

Dexmedetomidine to reduce vasopressor resistance in refractory septic shock: Protocol for a double-blind randomized controlled pilot trial (ADRESS Pilot study).

IntroductionRefractory septic shock (RSS) is characterized by high vasopressor requirements, as a consequence of vasopressor resistance, which may be caused or enhanced by sympathetic hyperactivation. Experimental models and clinical trials show a reduction in vasopressor requirements and improved microcirculation compared to conventional sedation. Dexmedetomidine did not reduce mortality in clinical trials, but few septic shock patients were enrolled. This pilot trial aims to evaluate vasopressor re-sensitization with dexmedetomidine and assess the effect size, in order to design a larger trial.MethodsThis is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, comparing dexmedetomidine versus placebo in RSS patients with norepinephrine dose ≥0.5μg/kg/min. The primary outcome is blood pressure response to phenylephrine challenge, 6 hours after completion of a first challenge, after study treatment initiation. Secondary outcomes include feasibility and safety outcomes (bradycardia), mortality, vasopressor requirements, heart rate variability, plasma and urine catecholamines levels. The sample size is estimated at 32 patients to show a 20% improvement in blood pressure response to phenylephrine. Randomization (1:1) will be stratified by center, sedation type and presence of liver cirrhosis. Blood pressure and ECG will be continuously recorded for the first 24 h, enabling high-quality data collection for the primary and secondary endpoints. The study was approved by the ethics committee “Sud-Est VI” (2019-000726-22) and patients will be included after informed consent.DiscussionThe present study will be the first randomized trial to specifically address the hemodynamic effects of dexmedetomidine in patients with septic shock. We implement a high-quality process for data acquisition and recording in the first 24 h, ensuring maximal quality for the evaluation of both efficacy and safety outcomes, as well as transparency of results. The results of the study will be used to elaborate a full-scale randomized controlled trial with mortality as primary outcome in RSS patients.Trial registrationRegistered with ClinicalTrials.gov (NCT03953677). Registered 16 May 2019, https://clinicaltrials.gov/ct2/show/NCT03953677.

Outcomes and Prognostic Factors of Pulmonary Hypertension Patients Undergoing Emergent Endotracheal Intubation.

Background: Emergent endotracheal intubations (ETI) in pulmonary hypertension (PH) patients are associated with increased mortality. Post-intubation interventions that could increase survivability in this population have not been explored. We evaluate early clinical characteristics and complications following emergent endotracheal intubation and seek predictors of adverse outcomes during this post-intubation period. Methods: Retrospective cohort analysis of adult patients with groups 1 and 3 PH who underwent emergent intubation between 2005-2021 in medical and liver transplant ICUs at a tertiary medical center. PH patients were compared to non-PH patients, matched by Charlson Comorbidity Index. Primary outcomes were 24-h post-intubation and inpatient mortalities. Various 24-h post-intubation secondary outcomes were compared between PH and control cohorts. Results: We identified 48 PH and 110 non-PH patients. Pulmonary hypertension was not associated with increased 24-h mortality (OR 1.32, 95%CI 0.35-4.94, P = .18), but was associated with inpatient mortality (OR 4.03, 95%CI 1.29-12.5, P = .016) after intubation. Within 24 h post-intubation, PH patients experienced more frequent acute kidney injury (43.5% vs. 19.8%, P = .006) and required higher norepinephrine dosing equivalents (6.90 [0.13-10.6] mcg/kg/min, vs. 0.20 [0.10-2.03] mcg/kg/min, P = .037). Additionally, the median P/F ratio (PaO2/FiO2) was lower in PH patients (96.3 [58.9-201] vs. 233 [146-346] in non-PH, P = .001). Finally, a post-intubation increase in PaCO2 was associated with mortality in the PH cohort (post-intubation change in PaCO2 +5.14 ± 16.1 in non-survivors vs. -18.7 ± 28.0 in survivors, P = .007). Conclusions: Pulmonary hypertension was associated with worse outcomes after emergent endotracheal intubation than similar patients without PH. More importantly, our data suggest that the first 24 hours following intubation in the PH group represent a particularly vulnerable period that may determine long-term outcomes. Early post-intubation interventions may be key to improving survival in this population.

Abstract P3023: The Regulatory Role Of Mir-21 In Heart Failure With Preserved Ejection Fraction (hfpef)

Introduction: Coronary microvascular dysfunction (CMD) is characterized by impaired endothelial-dependent vasodilation. These impairments are seen in diabetic cardiomyopathy, ischemia with no obstructive coronary artery disease, and heart failure with preserved ejection fraction (HFpEF), but detailed mechanisms have yet to be elucidated. Moreover, how microRNA (miR-21) regulates CMD in HFpEF is not entirely understood. Methods: miR-21 knockout and wild-type (WT) mice were fed a diet high in fat and sugar (HFHS) for 6 months and blood lipid and glucose were measured. Echocardiography and treadmill exercise exertion tests were performed to assess cardiac function. Myocardial blood flow (MBF) under stress was measured by contrast echocardiography or doppler after the treatment with different dosages of norepinephrine and mean arterial blood pressure was measured simultaneously by femoral pressure catheter. Cardiac fibrosis was detected using trichrome staining and molecular pathways were elucidated via gene and protein analysis. Results: Our preliminary data show decreased MBF during stress in WT mice fed a HFHS diet. While ejection fraction was not changed, cardiac index, stroke volume, and running distance were decreased. Furthermore, E/E’ ratio was increased in WT mice fed HFHS diet compared to the WT mice fed a chow diet, suggesting heart failure and impaired diastolic function with normal systolic function. Moreover, perivascular fibrosis was increased in the WT mice fed a HFHS diet compared to WT mice fed a chow diet. However, the ablation of miR-21 reversed all these changes in the mice fed a HFHS diet. Conclusions: miR-21 regulates CMD and ameliorated HFpEF. Further investigation will elucidate the pathways and mechanisms converging with miR-21 to regulate HFpEF.

Endovascular Perfusion Augmentation After Resuscitative Endovascular Balloon Occlusion of the Aorta Improves Renal Perfusion and Decreases Vasopressors

IntroductionResuscitative endovascular balloon occlusion of the aorta (REBOA) causes a severe ischemia-reperfusion injury. Endovascular Perfusion Augmentation for Critical Care (EPACC) has emerged as a hemodynamic/mechanical adjunct to vasopressors and crystalloid for the treatment of post-REBOA ischemia-reperfusion injury. The objective of the study is to examine the impact of EPACC as a tool for a wean from complete REBOA compared to standard resuscitation techniques. MethodsNine swine underwent anesthesia and then a controlled 30% blood volume hemorrhage with 30 min of supraceliac total aortic occlusion to create an ischemia-reperfusion injury. Animals were randomized to standardized critical care (SCC) or 90 min of EPACC followed by SCC. The critical care phase lasted 270 min after injury. Hemodynamic markers and laboratory values of ischemia were recorded. ResultsDuring the first 90 min the intervention phase SCC spent 60% (54%-73%) and EPACC spent 91% (88%-92%) of the time avoiding proximal hypotension (<60 mm Hg), P = 0.03. There was also a statistically significant decrease in cumulative norepinephrine dose at the end of the experiment between SCC (80.89 mcg/kg) versus EPACC (22.03 mcg/kg), P = 0.03. Renal artery flow during EPACC was similar compared to SCC during EPACC, P = 0.19. But during the last hour of the experiment (after removal of aortic balloon) the renal artery flow in EPACC (2.9 mL/kg/min) was statistically significantly increased compared to SCC (1.57 mL/min/kg), P = 0.03. There was a statistically significant decrease in terminal creatinine in the EPACC (1.7 mg/dL) compared to SCC (2.1 mg/dL), P = 0.03. ConclusionsThe 90 min of EPACC as a weaning adjunct in the setting of a severe ischemia-reperfusion injury after complete supraceliac REBOA provides improved renal flow with improvement in terminal creatinine compared to SCC with stabilized proximal hemodynamics and decreased vasopressor dose.

Comparative Dose-Response Study on the Infusion of Norepinephrine Combined with Crystalloid Coload versus Colloid Coload for Preventing Hypotension During Spinal Anesthesia for Cesarean Delivery.

BackgroundAlthough the optimal infusion dose of norepinephrine combined with crystalloid coload for preventing spinal anesthesia-induced hypotension (SAIH) for cesarean delivery has been established, the infusion regimen of norepinephrine combined with colloid coload has not been fully quantified. The objective of this study was to compare and determine the median effective dose (ED50) and 90% effective dose (ED90) of norepinephrine infusion combined with crystalloid coload versus colloid coload for preventing SAIH during cesarean delivery.MethodsTwo hundred parturients were randomly assigned to receive norepinephrine infusion at 0.02, 0.04, 0.06, 0.08, or 0.10 µg/kg/min in combination with 10 mL/kg crystalloid coload or colloid coload to prevent SAIH. The study period was defined as the interval from the commencement of intrathecal injection to delivery of the neonate. The primary outcome was non-occurrence of hypotension, defined as systolic blood pressure (SBP) less than 80% of the baseline before delivery. The ED50 and ED90 of norepinephrine infusion dose were determined using probit regression analysis. By calculating the 95% confidence intervals (CIs) of relative median potency to determine whether the prophylactic infusion of norepinephrine requirement was different between the two groups.ResultsThe derived ED50 and ED90 of norepinephrine infusion combined with crystalloid coload were 0.030 (95% CIs 0.020 to 0.038) and 0.097 (95% CIs 0.072 to 0.157) µg/kg/min, respectively. The ED50 and ED90 of norepinephrine infusion combined with colloid coload were 0.021 (95% CIs 0.013 to 0.029) and 0.070 (95% CIs 0.053 to 0.107) µg/kg/min, respectively. The estimate of relative median potency for norepinephrine between the two groups was 1.37 (95% CIs 0.94 to 2.23).ConclusionUnder the conditions of this study, 10 mL/kg colloid coload reduced the dose of prophylactic norepinephrine infusion by approximately 30% in parturients during spinal anesthesia for cesarean delivery compared with the crystalloid coload.

Acute circulatory failure in critically ill patients with hemophagocytic syndrome.

Hemophagocytic syndrome (HS) is a rare life-threatening condition that can lead to multi organ failure and shock. Acute circulatory failure in these patients has been poorly studied. Objectives of this study were to describe characteristics of HS patients with shock, prognostic factors and impact of etoposide infusion on hemodynamic parameters. This is a monocenter, retrospective, observational cohort study in a French tertiary intensive care unit (ICU). All adult critically ill patients with HS managed in the ICU between 2007 and 2017, requiring vasopressors (norepinephrine) and etoposide infusion. Thirty-four patients were included. Two-third (n = 25) were of male gender and median age was 48 years [IQR 34-62]. Shock (n = 14, 41%) and acute respiratory failure (n = 8, 23.5%) were the main initial reasons for ICU admission. The most common HS trigger was underlying hematological malignancy (n = 26; 76%), followed by infectious diseases in 3 patients (9%) and auto immune diseases in 2 (6%) patients. Median SOFA score at ICU admission was 14 [10-17]. A majority of patients required mechanical ventilation (n = 29, 85%) and initial median lactate level was 3.7 mmol/L [2.9-6.9]. Hospital mortality rate was 53% (n = 18) and was associated with SOFA score and renal replacement therapy in univariate analysis. All patients received broad spectrum antibiotics under suspicion of septic shock. In 17 patients, 21 nosocomial infections were documented, mainly from bacterial origin. Etoposide infusion was followed by decreased norepinephrine doses despite an increase in lactate level, while no degradation in mean arterial pressure, heart rate or renal function were identified. Hospital mortality remains high in critically ill HS patients with shock, but a significant improvement of hemodynamic parameters is observed following etoposide infusion, suggesting that an aggressive initial supportive care is crucial in these patients.

Sepsis affects kidney graft function and one-year mortality of the recipients in contrast with systemic inflammatory response.

BackgroundInfections remain a major cause of morbidity and mortality after kidney transplantation. The aim of our study was to determine the effect of sepsis on kidney graft function and recipient mortality.MethodsA prospective, observational, single-center study was performed. Selected clinical and biochemical parameters were recorded and compared between an experimental group (with sepsis, n = 34) and a control group (with systemic inflammatory response syndrome, n = 31) comprising kidney allograft recipients.ResultsSepsis worsened both patient (HR = 14.77, p = 0.007) and graft survival (HR = 15.07, p = 0.007). Overall one-year mortality was associated with age (HR = 1.08, p = 0.048), APACHE II score (HR = 1.13, p = 0.035), and combination immunosuppression therapy (HR = 0.1, p = 0.006), while graft survival was associated with APACHE II (HR = 1.25, p = 0.004) and immunosuppression. In sepsis patients, mortality correlated with the maximal dose of noradrenalin (HR = 100.96, p = 0.008), fungal infection (HR = 5.64, p = 0.024), SAPS II score (HR = 1.06, p = 0.033), and mechanical ventilation (HR = 5.97, p = 0.033), while graft survival was influenced by renal replacement therapy (HR = 21.16, p = 0.005), APACHE II (HR = 1.19, p = 0.035), and duration of mechanical ventilation (HR = 1.01, p = 0.015).ConclusionIn contrast with systemic inflammatory response syndrome, septic kidney allograft injury is associated with early graft loss and may represent a significant risk of mortality.

Factors influencing accuracy when preparing injectable drug concentrations in appliance with clinical practice: a norepinephrine case study

Errors in injectable preparations with high-risk drugs can be fatal. This study aimed to identify the factors influencing the accuracy of high-risk injectable drug concentrations in appliances used for intensive...

A Prospective Randomized Study Comparing the Bolus Doses of Norepinephrine and Phenylephrine for the Treatment of Spinal Induced Hypotension in Cesarean Section.

Background: Spinal anesthetic-induced hypotension is the most worrisome complication for patients undergoing cesarean section under spinal anesthesia. The present study compares norepinephrine and phenylephrine bolus for the treatment of hypotension during spinal anesthesia for cesarean section.Methods: One hundred twenty- six women aged between 22 and 40 years with singleton pregnancy classified to the American Society of Anesthesiologists (ASA) physical class I and II posted for elective cesarean section under spinal anesthesia were randomly divided into two groups of 63 each. Group I patients received phenylephrine 50 mcg (microgram) as an intravenous bolus, and Group II received 4 mcg of norepinephrine as an intravenous bolus to treat spinal hypotension.Results: On comparing the demographic data of the patients in terms of age, weight, height, ASA Grade, level of block and surgery time no significant differences were found between the groups. Similarly, the fetal parameters were found to be not significantly different between the groups. However, the number of bolus doses of vasopressors required for the treatment of spinal-induced hypotension was significantly reduced in Group II (p=0.02). The frequency of bradycardia was found to be higher in patients who were given phenylephrine as compared to patients administered noradrenaline boluses (p=0.03). Five (7.93%) patients had shivering in Group I, while similar episodes were observed in 10 (15.87%) patients (p=0.05). Moreover, no significant difference was observed in comparing the heart rate and mean arterial pressure between the groups.Conclusion: Intermittent boluses of norepinephrine are found to be effective in the management of spinal‑induced hypotension during caesarean section.

Addition of terlipressin to norepinephrine in septic shock and effect of renal perfusion: a pilot study

Purpose Terlipressin improves renal function in patients with septic shock. However, the mechanism remains unclear. Here, we aimed to evaluate the effects of terlipressin on renal perfusion in patients with septic shock. Materials and Methods This pilot study enrolled patients with septic shock in the intensive care unit of the tertiary hospital from September 2019 to May 2020. We randomly assigned patients to terlipressin and usual care groups using a 1:1 ratio. Terlipressin was intravenously pumped at a rate of 1.3 μg/kg/hour for 24 h. We monitored renal perfusion using renal contrast-enhanced ultrasound (CEUS). The primary outcome was peak sonographic signal intensity (a renal perfusion parameter monitored by CEUS) at 24 h after enrollment. Results 22 patients were enrolled in this study with 10 in the terlipressin group and 12 in the usual care group. The baseline characteristics of patients between the two groups were comparable. The peak sonographic signal intensity at 24 h after enrollment in the terlipressin group (60.5 ± 8.6 dB) was significantly higher than that in the usual care group (52.4 ± 7.0 dB; mean difference, 7.1 dB; 95% CI, 0.4–13.9; adjusted p = .04). Patients in the terlipressin group had a lower time to peak, heart rates, norepinephrine dose, and a higher stroke volume at 24 h after enrollment. No significant difference in the urine output within 24 h and incidence of acute kidney injury within 28 days was found between the two groups. Conclusions Terlipressin improves renal perfusion, increases stroke volume, and decreases norepinephrine dose and heart rates in patients with septic shock.

Evaluation of vasopressin use in the management of refractory shock in patients admitted to the intensive care unit

Refractory shock is characterized by hemodynamic instability unresponsive to norepinephrine with a high mortality rate. As there are still doubts regarding the pharmacological benefit of the vasopressin addition, this retrospective study aimed to assess the profile of vasopressin use in the intensive care unit of a university hospital in Paraná, Brazil. The information collected was obtained through the analysis of electronic medical records. 73 patients with refractory shock, mainly of septic etiology (61.6%), were included. The dose (μg/Kg/minute) and duration of norepinephrine, upon finding refractoriness, was 35.6% infusion &lt; 1, 34, 3% of 1-1.9, 30.1% &gt; 2 and mean time of 1.5 days. High mortality (80.8%) was observed, with a mean hospital stay of 8.2 days. Median survival after vasopressin infusion was 4.5 days until the unfavorable outcome. Still, 80.5% of patients used other adjuvant therapy, 71.2% being corticotherapy and 9.6% dobutamine. Due to the great variability, it was not possible to define a pattern of use. There were limitations in the analysis due to the lack of clinical and prognostic information. However, the need for deepening scientific discussions and continuous updating of protocols that guide management is highlighted.

Comparison of the effects of vitamin C and thiamine on refractory hypotension in patients with sepsis: A randomized controlled trial.

The study aimed to compare the effect of thiamine and ascorbic acid (AA) on mortality, sequential organ failure assessment (SOFA) score, duration and dose of vasopressor support, and need for renal replacement therapy (RRT) in patients with septic shock with refractory hypotension. Consenting adult patients with septic shock and refractory hypotension were included in this study. Patients were divided into three groups: Group A received 100 ml of balanced salt solution 8 hourly, Group B received 2 mg/kg of thiamine 8 hourly, Group C received 25 mg/kg of AA 8 hourly intravenous (IV) for 72 h. All patients received IV infusion of hydrocortisone 200 mg/day for 72 h. Serum lactate, dose and duration of vasopressor support, SOFA score, need for RRT and hospital mortality were analyzed. The SOFA Score was significantly lower in Group B than in Group A and C at 24, 48, and 72 h. Dosage of norepinephrine was lower in Group B at 66 h and after that, whereas in Groups A and C, it was comparable at all time points. Mortality in Group B was significantly lower but comparable in Groups A and C. The need for RRT was significantly lower in Group B (44%) compared to the control group (88%) but comparable in Group C (76%). In patients with septic shock treated with hydrocortisone, co-treatment with thiamine led to earlier correction of organ dysfunction, reduced need for RRT, and improved mortality compared to patients treated with AA or balanced salt solution. The addition of AA did not yield measurable benefits beyond hydrocortisone alone.

Norepinephrine versus phenylephrine for postspinal hypotension in parturients undergoing cesarean section: a systematic review and meta-analysis.

Multiple studies have compared varying prophylactic and therapeutic doses of norepinephrine and phenylephrine given as either intermittent bolus or fixed-rate infusion to combat postspinal hypotension in patients undergoing cesarean section (CS). We conducted a systematic review to figure out the best alternative to treat postspinal hypotension. PubMed and Cochrane databases were extensively searched for eligible RCTs. A total of 15 studies were found eligible and analyzed for the incidence of maternal bradycardia as the primary outcome and other maternal adverse effects, fetal acidosis and Apgar scores at 1 and 5 min as the secondary outcome. Data was analyzed using Review Manager Version 5.3. software. There was no significant difference in the efficacy of norepinephrine and phenylephrine for managing postspinal hypotension (OR=1.15 [95% CI: 0.91-1.45], P=0.24, I2=0%,moderate quality) in parturients undergoing CS. Odds of incidence of maternal bradycardia decrease significantly by 61% with norepinephrine versus phenylephrine (OR=0.39 [95% CI: 0.31-0.49], P<0.00001, I2=27%, high quality evidence). Significant higher umbilical artery mean pH values were observed with NE versus PE (MD=0.0 [95% CI: 0.00 to 0.01], P=0.03), although not clinical relevant. However, no significant difference was found in the incidence of other maternal adverse effects and fetal outcomes. Comparable efficacy for management of postspinal hypotension, though, norepinephrine was found to cause less incidence of maternal bradycardia as compared to phenylephrine.