Limb Necrosis in the Setting of Vasopressor Use.

BACKGROUND: It remains poorly understood why only some hemodynamically unstable patients who receive aggressive treatment with vasopressor medications develop limb necrosis. OBJECTIVE: To determine the incidence of limb necrosis and the factors associated with it following high-dose vasopressor therapy. METHODS: A retrospective case-control medical records review was performed of patients aged 18 to 89 years who received vasopressor therapy between 2012 and 2021 in a single academic medical center. The study population was stratified by the development of limb necrosis following vasopressor use. Patients who experienced necrosis were compared with age- and sex-matched controls who did not experience necrosis. Demographic information, comorbidities, and medication details were recorded. RESULTS: The incidence of limb necrosis following vasopressor administration was 0.25%. Neither baseline demographics nor medical comorbidities differed significantly between groups. Necrosis was present in the same limb as the arterial catheter most often for femoral catheters. The vasopressor dose administered was significantly higher in the necrosis group than in the control group for ephedrine (P = .02) but not for the other agents. The duration of therapy was significantly longer in the necrosis group than in the control group for norepinephrine (P = .001), epinephrine (P = .04), and ephedrine (P = .01). The duration of vasopressin administration did not differ significantly between groups. CONCLUSION: The findings of this study suggest that medication-specific factors, rather than patient and disease characteristics, should guide clinical management of necrosis in the setting of vasopressor administration.

The effect of vasopressor agents on pressure injury development in intensive care patients.

BACKGROUND: Vasopressors are life-saving agents that increase mean arterial pressure. The pharmacodynamic features of these agents and previous studies suggest that vasopressors may be an essential risk factor in developing pressure injuries. OBJECTIVE: This study aimed to examine the effect of vasopressors in medical-surgical intensive care patients on pressure injury development. DESIGN AND SETTINGS: This retrospective and correlational study was conducted between March 2021- May 2022. The electronic patient data were obtained from 148 surgical and medical patients exposed to vasopressor agents in the intensive care unit. Data on patients' demographic and clinical characteristics were evaluated using descriptive statistical methods (number, percentage, mean, standard deviation). Logistic regression modelling was used to assess independent relationships with pressure injury risk; results are reported as odds ratios (OR) and 95% confidence intervals (CI). RESULTS: All patients were given norepinephrine agents, and dopamine infusion secondary to norepinephrine was found in only 28.3 % of patients (n = 42). Pressure injury incidence was 43.2 % (n = 64). Duration of norepinephrine infusion was recognized as an independent risk factor for ICU-acquired pressure injury development (OR 1.22, 95 % CI 1.11-1.35), while a medical admission diagnosis (instead of surgical) was protective against pressure injury risk (OR 0.24, 95 % CI 0.10-0.59). CONCLUSION: This study indicated that duration of norepinephrine infusion is a significant risk factor for pressure injury development. IMPLICATIONS FOR CLINICAL PRACTICE: Although norepinephrine use cannot be avoided entirely, its administration may be an early warning for nurses to increase pressure injury prevention strategies. Skin evaluation should be performed more frequently, and preventive strategies should be implemented meticulously. This study was registered on clincialtrials.gov (Identifier: NCT06163352).

Association Between Intraoperative Noradrenaline Infusion and Outcomes in Older Adult Patients Undergoing Major Non-Cardiac Surgeries: A Retrospective Propensity Score-Matched Cohort Study.

Background: Noradrenaline (NA) is commonly used intraoperatively to prevent fluid overload and maintain hemodynamic stability. Clinical studies provided inconsistent results concerning the effect of NA on postoperative outcomes. As aging is accompanied with various diseases and has the high possibility of the risk for postoperative complications, we hypothesized that intraoperative NA infusion in older adult patients undergoing major non-cardiac surgeries might potentially exert adverse outcomes. Methods: In this retrospective propensity score-matched cohort study, older adult patients undergoing major non-cardiac surgeries were selected, 1837 receiving NA infusion during surgery, and 1072 not receiving NA. The propensity score matching was conducted with a 1:1 ratio and 1072 patients were included in each group. The primary outcomes were postoperative in-hospital mortality and complications. Results: Intraoperative NA administration reduced postoperative urinary tract infection (OR:0.124, 95% CI:0.016-0.995), and had no effect on other postoperative complications and mortality, it reduced intraoperative crystalloid infusion (OR:0.999, 95% CI:0.999-0.999), blood loss (OR: 0.998, 95% CI: 0.998-0.999), transfusion (OR:0.327, 95% CI: 0.218-0.490), but increased intraoperative lactate production (OR:1.354, 95% CI:1.051-1.744), and hospital stay (OR:1.019, 95% CI:1.008-1.029). Conclusion: Intraoperative noradrenaline administration reduces postoperative urinary tract infection, and does not increase other postoperative complications and mortality, and can be safely used in older adult patients undergoing major non-cardiac surgeries.

Adverse Events of Peripherally Administered Norepinephrine During Surgery: A Prospective Multicenter Study.

BACKGROUND: Perioperative treatment of hypotension by intravenous administration of norepinephrine in a peripheral vein can lead to adverse events, for example, tissue necrosis. However, the incidence and severity of adverse events during perioperative administration are unknown. METHODS: This was a prospective observational study conducted at 3 Swedish hospitals from 2019 to 2022. A total of 1004 patients undergoing surgery, who met the criteria for perioperative peripheral norepinephrine administration, were included. The infusion site was inspected regularly. If swelling or paleness of skin was detected, the infusion site was changed to a different peripheral line. Systolic blood pressure and pulse frequency were monitored during the infusion time and defined as adverse events at >220 mm Hg and <40 beats•min -1 . In case of adverse events, patients were observed for up to 48 hours. The primary outcome was prevalence of extravasation, defined as swelling around the infusion site. Secondary outcomes were all types of adverse events and associations between predefined clinical variables and risk of adverse events. RESULTS: We observed 2.3% (95% confidence interval [CI], 1.4%-3.2%) extravasation of infusion and 0.9% (95% CI, 0.4%-1.7%) bradycardia. No cases of tissue necrosis or severe hypertension were detected. All adverse events had dissipated spontaneously within 48 hours. Proximal catheter placement was associated with more adverse events. CONCLUSIONS: Extravasation of peripherally administrated norepinephrine in the perioperative period occurred at similar rates as in previous studies in critically ill patients. In our setting, where we regularly inspected the infusion site and shifted site in case of swelling or paleness of skin, we observed no case of severe adverse events. Given that severe adverse events were absent, the potential benefit of this preventive approach requires confirmation in a larger population.

Comparative efficacy of terlipressin and norepinephrine for treatment of hepatorenal syndrome-acute kidney injury: A systematic review and meta-analysis.

The treatment of choice for hepatorenal syndrome-acute kidney injury (HRS-AKI) is vasoconstrictor therapy in combination with albumin, preferably norepinephrine or terlipressin as recommended by recent guidelines. In the absence of larger head-to-head trials comparing the efficacy of terlipressin and norepinephrine, meta-analysis of smaller studies can provide insights needed to understand the comparative effects of these medications. Additionally, recent changes in the HRS diagnosis and treatment guidelines underscore the need for newer analyses comparing terlipressin and norepinephrine. In this systematic review, we aimed to assess reversal of hepatorenal syndrome (HRS) and 1-month mortality in subjects receiving terlipressin or norepinephrine for the management of HRS-AKI. We searched literature databases, including PubMed, Cochrane, Clinicaltrials.gov, International Clinical Trials Registry Platform, Embase, and ResearchGate, for randomized controlled trials (RCTs) published from January 2007 to June 2023 on June 26, 2023. Only trials comparing norepinephrine and albumin with terlipressin and albumin for the treatment of HRS-AKI in adults were included, and trials without HRS reversal as an endpoint or nonresponders were excluded. Pairwise meta-analyses with the random effects model were conducted to estimate odds ratios (ORs) for HRS reversal and 1-month mortality as primary outcomes. Additional outcomes assessed, included HRS recurrence, predictors of response, and incidence of adverse events (AEs). We used the Cochrane risk of bias assessment tool for quality assessment. We included 7 RCTs with a total of 376 subjects with HRS-AKI or HRS type 1. This meta-analysis showed numerically higher rates of HRS reversal (OR 1.33, 95% confidence interval [CI] [0.80-2.22]; P = 0.22) and short-term survival (OR 1.50, 95% CI [0.64-3.53]; P = 0.26) with terlipressin, though these results did not reach statistical significance. Terlipressin was associated with AEs such as abdominal pain and diarrhea, whereas norepinephrine was associated with cardiovascular AEs such as chest pain and ischemia. Most of the AEs were reversible with a reduction in dose or discontinuation of therapy across both arms. Of the terlipressin-treated subjects, 5.3% discontinued therapy due to serious AEs compared to 2.7% of the norepinephrine-treated subjects. Limitations of this analysis included small sample size and study differences in HRS-AKI diagnostic criteria. As more studies using the new HRS-AKI criteria comparing terlipressin and norepinephrine are completed, a clearer understanding of the comparability of these 2 therapies will emerge.

Vasopressin Initiation as a Second-Line VasoPressor in Early Septic Shock (VISPSS).

BACKGROUND: Vasopressin is recommended as a second-line vasoactive agent for the management of septic shock; however, a paucity of data to guide its optimal use remains. The aim was to evaluate the effect of time-to vasopressin initiation and norepinephrine (NE) dose at vasopressin initiation on clinical outcomes in patients presenting with septic shock. METHODS: This was a multi-centered, retrospective, observational study conducted in patients with septic shock. Patients were divided into 2 groups: patients initiated on vasopressin when NE-equivalent dose (NEE) < 0.25 mcg/kg/min or ≥ 0.25 mcg/kg/min. The primary outcome was time-to-vasopressor discontinuation (hours). Secondary outcomes included 28-day in-hospital mortality, intensive care unit (ICU) length of stay (LOS), fluid balance after 72 hours, and the change in NEE at 12 hours. RESULTS: A total of 302 patients were included in this study. After propensity-score matching, 73 patients in each group were identified for analysis. There was no significant difference in the time-to-vasopressor discontinuation (hours) between the groups (88.8 [55-187.5] vs 86.7 [47-172]); p = 0.7815). Fluid balance (mL) at 72 hours was significantly lower when vasopressin was initiated at NEE < 0.25 mcg/kg/min (1769 [71-7287] vs 5762 [1463-8813]; p = 0.0077). A multivariable linear regression showed shorter time to shock resolution with earlier vasopressin initiation, defined as within 4 hours (p < 0.05). CONCLUSION: In this propensity-score matched cohort, vasopressin initiation at NEE < 0.25 mcg/kg/min was not associated with shorter vasopressor duration. There was a lower fluid balance at 72 hours when vasopressin was initiated at lower NE doses.

A randomized open label, parallel-group study to evaluate the hemodynamic effects of Cafedrine/Theodrenaline vs Noradrenaline in the treatment of intraoperative hypotension after induction of general anesthesia: the "HERO" study design and rationale.

OBJECTIVE: Intraoperative arterial hypotension (IOH) is associated with poor patient outcome. This study aims to compare the hemodynamic effects of Cafedrine/Theodrenaline (C/T) and Noradrenaline (NA) for the treatment of hypotension in patients who develop IOH after anesthesia induction. RESEARCH DESIGN AND METHODS: This is a national, randomized, parallel-group, multicenter, and open-label study. Adult patients (≥50 years, ASA-classification III-IV) who undergo elective surgery will be included. When IOH (MAP <70 mmHg) develops, C/T or NA will be given as a bolus injection ("bolus phase", 0-20 min after initial application) and subsequently as continuous infusion ("infusion phase", 21-40 min after initial application) to achieve MAP = 90 mmHg. Hemodynamic data are captured in real time by advanced hemodynamic monitoring. RESULTS: Primary endpoints, i.e. the treatment-related difference in average mean arterial pressure (MAP) during the "infusion phase" and the treatment-related difference in average cardiac index during the "bolus phase" are assessed (fixed-sequence method). Non-inferiority of C/T compared to NA in achieving 90 mmHg (MAP) when applied as continuous infusion is hypothesized. In addition, superiority of C/T over NA, applied as bolus injection, in increasing cardiac index is postulated. It is estimated that 172 patients are required to establish statistical significance with a power of 90%. After adjusting for ineligibility and dropout rate, 220 patients will be screened. CONCLUSION: This clinical trial will yield evidence for marketing authorization of C/T applied as continuous infusion. Additionally, the effects of C/T compared to NA on cardiac index will be assessed. First results of the "HERO"-study are expected in 2024. DRKS identifier: DRKS00028589. EudraCT identifier: 2021-001954-76.

Prevention of spinal hypotension during cesarean section: A systematic review and Bayesian network meta-analysis based on ephedrine, phenylephrine, and norepinephrine.

AIM: The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine, phenylephrine, and norepinephrine for the prevention of spinal hypotension during cesarean section. METHODS: The Web of Science, PubMed, EMBASE, Cochrane Library were searched until to May 20, 2022. The indicators included incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, umbilical artery pH, and Apgar scores. RESULTS: About 3125 related records were obtained and 17 RCTs met our eligibility criteria. Based on the results, prophylactic bolus injection of 21-30 mg ephedrine (82%) was the best efficacious option for preventing hypotension, followed by 13-16 µg norepinephrine and 81-120 mg phenylephrine; 121-150 µg phenylephrine had the highest probability (62%) caused reactive hypertension, followed by 11-30 mg ephedrine; phenylephrine was most likely to cause bradycardia in a dose-dependent manner; 81-120 µg phenylephrine had the highest probability (37%) which associated with IONV; 6-12 µg norepinephrine (31%) had the lowest influence on IONV and had highest probability (34%) associated with improving umbilical arterial pH; 13-16 µg norepinephrine had highest probability (67% at 1 min, 49% at 5 min) which associated with improving Apgar scores. CONCLUSIONS: Based on this study, 5-10 mg ephedrine and 13-16 µg norepinephrine prophylactic bolus injection may be the optimum dosage of three drugs prevent spinal-induced hypotension, which has the least impact on maternal and neonatal outcomes.

Timing of vasopressin initiation and mortality in patients with septic shock: analysis of the MIMIC-III and MIMIC-IV databases.

BACKGROUND: vasopressin is commonly used as a second-line vasopressor for patients with septic shock, but the optimal timing of initiation is uncertain. This study was designed to investigate when vasopressin initiation may be beneficial for 28-day mortality in septic shock patients. METHODS: This was a retrospective observational cohort study from the MIMIC-III v1.4 and MIMIC-IV v2.0 databases. All adults diagnosed with septic shock according to Sepsis-3 criteria were included. Patients were stratified into two groups based on norepinephrine (NE) dose at the time of vasopressin initiation, defined as the low doses of NE group (NE<0.25 µg/kg/min) and the high doses of NE group (NE ≥ 0.25 µg/kg/min). The primary end-point was 28-day mortality after diagnosis of septic shock. The analysis involved propensity score matching (PSM), multivariable logistic regression, doubly robust estimation, the gradient boosted model, and an inverse probability-weighting model. RESULTS: A total of 1817 eligible patients were included in our original cohort (613 in the low doses of NE group and 1204 in the high doses of NE group). After 1:1 PSM, 535 patients from each group with no difference in disease severity were included in the analysis. The results showed that vasopressin initiation at low doses of NE was associated with reduced 28-day mortality (odds ratio [OR] 0.660, 95% confidence interval [CI] 0.518-0.840, p < 0.001). Compared with patients in the high doses of NE group, patients in the low doses of NE group received significantly shorter duration of NE, with less intravenous fluid volume on the first day after initiation of vasopressin, more urine on the second day, and longer mechanical ventilation-free days and CRRT-free days. Nevertheless, there were no significant differences in hemodynamic response to vasopressin, duration of vasopressin, and ICU or hospital length of stay. CONCLUSIONS: Among adults with septic shock, vasopressin initiation when low-dose NE was used was associated with an improvement in 28-day mortality.

Adverse effects related with norepinephrine through short peripheral venous access: Scoping review.

Peripheral administration of norepinephrine is restricted due to the association of extravasation with tissue necrosis. METHOD: Scoping review with the objective of describing the adverse effects related to the administration of norepinephrine through short peripheral venous access and the characteristics of drug administration in patients hospitalized in ICU, surgery, and emergency services. RESULTS: 12 studies with heterogeneous characteristics by size and type of population were included. The proportion of complications associated with peripheral norepinephrine administration was less than 12% in observational studies and it was less than 2% in those that used doses less than 0.13µg/kg/min, and concentrations less than 22.3µg/mL. The main associated complication was extravasation and there were no cases of tissue necrosis at the venipuncture site, some extravasation cases were treated with phentolamine, terbutaline or topical nitroglycerin. The drug administration time ranged between 1 and 528hours with a weighted mean of 2.78h. CONCLUSION: The main adverse effect was extravasation, no additional complications occurred, phentolamine and terbutaline seem to be useful, and its availability is a necessity. It is essential for the nursing staff to carry out a close assessment and comprehensive care in patients receiving norepinephrine by peripheral route.

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

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

SSRI/SNRI -induced Hyponatremia: A Case Series of 26 Patients in a Single Institution from 2018 to 2020.

Antidepressant medications are widely used by patients with depression or a depressive disorder. In spite of a generally favorable safety profile of selective serotonin reuptake inhibitors or serotonin - norepinephrine reuptake inhibitors (SSRI/SNRI), several cases of a possible connection between SSRI/SNRI and hyponatremia have been reported. To describe the clinical characteristics of patients with hyponatremia after SSRI/SNRI exposure, and to examine the association between SSRI/SNRI exposure and the presence of hyponatremia in a Chinese population. A retrospective single-center case series study. We performed a retrospective evaluation of inpatients with SSRI/SNRI-induced hyponatremia from a single institution in China between 2018 and 2020. Clinical data were obtained through review of medical records. Patients who met the initial inclusion criteria but did not develop hyponatremia acted as controls. The study was approved by the Clinical Research Ethics Board of Beijing Hospital (Beijing, P.R. China). We identified 26 patients with SSRI/SNRI-induced hyponatremia. The incidence rate of hyponatremia was 1.34% (26/1937) in the study population. The mean age at diagnosis was 72.58 (±12.84) years, with a male: female ratio of 1:1.42. The duration between SSRI/SNRI exposure and the onset of hyponatremia was 7.65 (±4.88) days. The minimum serum sodium level was 2328.23 (±107.25) mg/dL in the study group. Seventeen patients (65.38%) received sodium supplements. Four patients (15.38%) switched to another antidepressant. Fifteen patients (57.69%) recovered by the time of discharge. There were significant differences in serum potassium, serum magnesium and serum creatinine level between the two groups (p < 0.05). The rate of use of sertraline was significantly higher in the study group compared with the control group (p < 0.05). This pattern was not found in other SSRI/SNRI (p > 0.05). The results of our study show that SSRI/SNRI exposure, in addition to hyponatremia, may also affect the level of serum potassium, serum magnesium and serum creatinine. A history of hyponatremia and exposure to SSRI/SNRI may be potential risk factors for the development of hyponatremia. Future prospective studies are needed to validate these findings.

Noradrenaline and Seizures: A Perspective on the Role of Adrenergic Receptors in Limbic Seizures.

BACKGROUND: Noradrenergic fibers originating from the locus coeruleus densely innervate limbic structures, including the piriform cortex, which is the limbic structure with the lowest seizure threshold. Noradrenaline (NA) modulates limbic seizures while stimulating autophagy through ß2- adrenergic receptors (AR). Since autophagy is related to seizure threshold, this perspective questions whether modulating ß2-AR focally within the anterior piriform cortex affects limbic seizures. OBJECTIVE: In this perspective, we analyzed a potential role for ß2-AR as an anticonvulsant target within the anterior piriform cortex, area tempestas (AT). METHODS: We developed this perspective based on current literature on the role of NA in limbic seizures and autophagy. The perspective is also grounded on preliminary data obtained by microinfusing within AT either a ß2-AR agonist (salbutamol) or a ß2-AR antagonist (butoxamine) 5 minutes before bicuculline. RESULTS: ß2-AR stimulation fully prevents limbic seizures induced by bicuculline micro-infusion in AT. Conversely, antagonism at ß2-AR worsens bicuculline-induced seizure severity and prolongs seizure duration, leading to self-sustaining status epilepticus. These data indicate a specific role for ß2-AR as an anticonvulsant in AT. CONCLUSION: NA counteracts limbic seizures. This relies on various receptors in different brain areas. The anterior piriform cortex plays a key role in patients affected by limbic epilepsy. The anticonvulsant effects of NA through ß2-AR may be related to the stimulation of the autophagy pathway. Recent literature and present data draw a perspective where ß2-AR stimulation while stimulating autophagy mitigates limbic seizures, focally within AT. The mechanism linking ß2-AR to autophagy and seizure modulation should be extensively investigated.

Manually Controlled, Continuous Infusion of Phenylephrine or Norepinephrine for Maintenance of Blood Pressure and Cardiac Output During Spinal Anesthesia for Cesarean Delivery: A Double-Blinded Randomized Study.

BACKGROUND: To counteract the vasoplegia induced by spinal anesthesia (SA) and maintain blood pressure (BP) during cesarean delivery, phenylephrine is currently recommended, but norepinephrine might offer superior preservation of cardiac output. We aimed to compare the hemodynamic effects of phenylephrine and norepinephrine administered by manually adjusted continuous infusion during elective cesarean delivery. METHODS: In this pragmatic, parallel-group, double-blind randomized controlled trial, 124 parturients scheduled for elective cesarean delivery under SA in a tertiary maternity in France, between February 2019 and December 2020, were randomized to receive norepinephrine at a starting rate of 0.05 µg·kg -1 ·min -1 (n = 62) or phenylephrine at a starting rate of 0.5 µg·kg -1 ·min -1 (n = 62). In both groups, the vasopressor infusion rate was then manually adjusted to maintain maternal systolic BP above 90% of the baseline value. The primary outcome, the change in cardiac index (CI) measured by thoracic bioreactance from SA to umbilical cord clamping, was analyzed through repeated measures analysis of variance and post hoc t tests. Secondary outcomes included maternal BP and neonatal outcomes. RESULTS: In the norepinephrine group, cardiac index was maintained between 90% and 100% of baseline from SA to umbilical cord clamping, whereas it was maintained at significantly lower values (81%-88%) in the phenylephrine group ( P = .001). The percentage of elapsed time with a mean maternal BP <65 mm Hg and with systolic BP <80% of the baseline value was higher in the phenylephrine group: 2.9% (7.3) vs 0.5% (1.8) (absolute risk difference [ARD], -2.4%; 95% confidence interval, -4.4 to -0.5; P = .012) and 8.5% (16.6) vs 2.3% (5.2) (ARD, -6.2%; 95% confidence interval, -10.6 to -1.8; P = .006). Excluding parturients with gestational diabetes, severe neonatal hypoglycemia was more common in the phenylephrine group at 19.6% (9/46) vs 4.1% (2/49) ( P = .02). The other neonatal outcomes did not differ significantly between the groups. CONCLUSIONS: When administered by manually adjusted infusion during SA for cesarean delivery, norepinephrine was associated with a higher CI; both infusions were effective for maintaining BP.

Optimal target blood pressure in elderly with septic shock (OPTPRESS) trial: study protocol for a randomized controlled trial.

BACKGROUND: Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. METHODS: A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80-85 mmHg (high-target) and 65-70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients' condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 µg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. DISCUSSION: The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

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

INTRODUCTION: 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. EVIDENCE ACQUISITION: 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. EVIDENCE SYNTHESIS: 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. CONCLUSIONS: Comparable efficacy for management of postspinal hypotension, though, norepinephrine was found to cause less incidence of maternal bradycardia as compared to phenylephrine.

Clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock.

To analyze the clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock. 100 patients with septic shock treated in our institution from May 2019 to May 2021 were recruited and randomly assigned to receive either norepinephrine (control group) or norepinephrine plus ulinastatin (experimental group) according to the treatment scheme. The treatment efficacy, time for shock improvement, intensive care unit (ICU) stay, total hospital stay, in-hospital mortality, 30-day survival, and changes in inflammatory factors (plasma C-reactive protein (CRP), serum lactic acid (LAC), serum procalcitonin (PCT), and interleukin-10 (IL-10)) before and after treatment were analyzed, and the sequential organ failure scores of the two groups were compared. The experimental group exhibited superior performance with respect to efficacy, ICU stays, and total hospital stay, in-hospital mortality to the control group (all P<0.05). After treatment, the experimental group presented lower levels of CRP, LAC, PCT and IL-10 and higher SOFA scores than the control group (P<0.05). Norepinephrine plus ulinastatin achieved remarkable results in the treatment of septic shock, improving the treatment efficiency, shortening the time for shock improvement and hospitalization, reducing hospital mortality, driving down the expression of inflammatory factors and enhancing the survival of patients, with high safety.

Clinical characteristics and factors associated with acute kidney injury among patients hospitalized with coronavirus disease: an observational retrospective study.

BACKGROUND: Coronavirus disease 19 (COVID-19) is a multisystemic disease with high incidence of acute kidney injury (AKI). OBJECTIVE: To describe the clinical characteristics and factors associated with AKI among patients hospitalized with COVID-19. DESIGN AND SETTING: Retrospective cohort conducted at Hospital Civil de Culiacan, Mexico. METHODS: We included 307 patients hospitalized due to COVID-19. AKI was defined and staged based on serum creatinine levels in accordance with the criteria of the Acute Kidney Injury Network (AKIN). Multivariate logistic regression analysis was used to determine factors associated with AKI. RESULTS: The patients' age was 56 ± 15 years (64.5% male). The incidence of AKI was 33.6% (n = 103). Overall, 53.4% of patients had community-acquired AKI, and 46.6% had hospital-acquired AKI. Additionally, 15.5% of them presented AKIN stage 1; 34% had AKIN stage 2; and 50.5% had AKIN stage 3. Hemodialysis was required for 10.7% of the patients. The factors associated with AKI were chronic kidney disease (odds ratio, OR: 10.8; P = 0.04), use of norepinephrine (OR: 7.3; P = 0.002), diabetes mellitus (OR: 2.9; P = 0.03), C-reactive protein level (OR: 1.005; P = 0.01) and COVID-19 severity index based on chest tomography (OR: 1.09; statistical trend, P = 0.07). Hospital stay (11 ± 7 days; P < 0.001) and mortality (83.5 versus 31.4%; P < 0.05) were greater among patients with AKI. CONCLUSION: AKI was a frequent and serious complication in our cohort of patients hospitalized with COVID-19, which was associated with high mortality and long hospital stay.