Management of hepatorenal syndrome and associated outcomes: a systematic reviews.

BACKGROUND: Hepatorenal syndrome (HRS), a multiorgan condition of acute kidney injury, is seen in advanced liver disease. This study aims to evaluate the current treatment for HRS. METHODS: The authors searched PubMed, Scopus and Google Scholar literature. After quality assessment, 31 studies were included in this review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology and the population, intervention, comparison and outcome scheme were used. We included human-controlled trials that evaluate the current treatment for HRS. Two authors independently screened articles for inclusion, extracted data and assessed the quality of included studies. RESULTS: This study investigated the studies conducted on the effects of different treatments on follow-up of HRS patients. We gathered 440 articles, so 31 articles remained in our study. Of which 24 articles were conducted on terlipressin versus placebo or other treatments (midodrine/octreotide, norepinephrine, etc) that showed the higher rate of HRS reversal was detected for terlipressin in 17 studies (10 of them were significant), 2 studies achieved an insignificant lower rate of the model for end-stage liver disease score for terlipressin, 15 studies showed a decreased mortality rate in the terlipressin group (4 of them were significant). CONCLUSION: This review showed that terlipressin has a significantly higher reversal rate of HRS than the other treatments. Even the results showed that terlipressin is more efficient than midodrine/octreotide and norepinephrine as a previous medication, in reverse HRS, increasing patient survival.

ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock.

BACKGROUND: Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock. METHODS: In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I/angiotensin-II ratio), and the change in renin from 0 to 3 h. RESULTS: We included n = 321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1 mmHg [95% CI 7.6-10.1], p < 0.0001), lower norepinephrine equivalent dose over 48-h (p = 0.0037), and lower study-drug dose over 48-h (p < 0.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi/ARB-unexposed (difference in treatment-effect: - 2.2 mmHg [95% CI - 7.0-2.6], pinteraction = 0.38), but a greater reduction in norepinephrine equivalent dose (pinteraction = 0.0031) and study-drug dose (pinteraction < 0.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi/ARB-unexposed (difference in treatment-effect: - 6.0 mmHg [95% CI - 11.5 to - 0.6], pinteraction = 0.0299), norepinephrine equivalent dose (pinteraction < 0.0001), and study-drug dose (pinteraction = 0.0008). Baseline renin levels and angiotensin-I/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients. CONCLUSIONS: In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock. Trial Registration ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

The scientific rationale and study protocol for the DPP3, Angiotensin II, and Renin Kinetics in Sepsis (DARK-Sepsis) randomized controlled trial: serum biomarkers to predict response to angiotensin II versus standard-of-care vasopressor therapy in the treatment of septic shock.

BACKGROUND: Data to support the use of specific vasopressors in septic shock are limited. Since angiotensin II (AT2) was approved by the Food and Drug Administration in 2017, multiple mechanistically distinct vasopressors are available to treat septic shock, but minimal data exist regarding which patients are most likely to benefit from each agent. Renin and dipeptidyl peptidase 3 (DPP3) are components of the renin-angiotensin-aldosterone system which have been shown to outperform lactate in predicting sepsis prognosis, and preliminary data suggest they could prove useful as biomarkers to guide AT2 use in septic shock. METHODS: The DARK-Sepsis trial is an investigator-initiated industry-funded, open-label, single-center randomized controlled trial of the use of AT2 versus standard of care (SOC) vasopressor therapy in patients admitted to the intensive care unit (ICU) with vasodilatory shock requiring norepinephrine ≥ 0.1 mcg/kg/min. In both groups, a series of renin and DPP3 levels will be obtained over the first 24 h of treatment with AT2 or SOC. The primary study outcome will be the ability of these biomarkers to predict response to vasopressor therapy, as measured by change in total norepinephrine equivalent dose of vasopressors at 3 h post-drug initiation or the equivalent timepoint in the SOC arm. To determine if the ability to predict vasopressor response is specific to AT2 therapy, the primary analysis will be the ability of baseline renin and DPP3 levels to predict vasopressor response adjusted for treatment arm (AT2 versus control) and Sequential Organ Failure Assessment (SOFA) scores. Secondary outcomes will include rates of acute kidney injury, need for mechanical ventilation and kidney replacement therapy, lengths of stay in the ICU and hospital, ICU and hospital mortality, and rates of prespecified adverse events. DISCUSSION: With an armamentarium of mechanistically distinct vasopressor agents now available, sub-phenotyping patients using biomarkers has the potential to improve septic shock outcomes by enabling treatment of the correct patient with the correct vasopressor at the correct time. However, this approach requires validation in a large definitive multicenter trial. The data generated through the DARK-Sepsis study will prove crucial to the optimal design and patient enrichment of such a pivotal trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05824767. Registered on April 24, 2023.

Norepinephrine versus phenylephrine on cerebral tissue oxygen saturation during prophylactic infusion to prevent spinal hypotension for Caesarean birth.

BACKGROUND: Phenylephrine may cause a reduction in maternal cerebral tissue oxygen saturation (SctO2) during Caesarean birth to prevent spinal hypotension; however, the effect of norepinephrine has not been assessed. We hypothesized that norepinephrine was more effective than phenylephrine in maintaining SctO2 when preventing spinal hypotension during Caesarean birth. METHODS: We conducted a randomized, double-blind, controlled study. Sixty patients were randomly assigned to prophylactic norepinephrine or phenylephrine to maintain blood pressure during spinal anesthesia for Caesarean birth. SctO2, systolic blood pressure, and heart rate were recorded. The primary outcome was the incidence of a 10% reduction of intraoperative SctO2 from baseline or more during Caesarean birth. RESULTS: The norepinephrine group had a lower incidence of more than 10% reduction of intraoperative SctO2 from baseline than that of the phenylephrine group (13.3% vs 40.0%, P = .02). The change in SctO2 after 5 minutes of norepinephrine infusion was higher than that after phenylephrine infusion (-3.4 ±â€…4.7 vs -6.2 ±â€…5.6, P = .04). The change in SctO2 after 10 minutes of norepinephrine infusion was higher than that after phenylephrine infusion (-2.5 ±â€…4.4 vs -5.4 ±â€…4.6, P = .006). The norepinephrine group showed greater left- and right-SctO2 values than the phenylephrine group at 5 to 10 minutes. However, the change in systolic blood pressure was comparable between the 2 groups. CONCLUSION: Norepinephrine was more effective than phenylephrine in maintaining SctO2 when preventing spinal hypotension during Caesarean birth. However, the changes in clinical outcomes caused by differences in SctO2 between the 2 medications warrant further studies.

Hemodynamic effects of noradrenaline in neonatal septic shock: a prospective cohort study.

BACKGROUND: The incidence of neonatal septic shock in low-income countries is 26.8% with a mortality rate of 35.4%. The evidence of the hemodynamic effects of noradrenaline in neonates remains sparse. This study was carried out to evaluate the effects of noradrenaline in neonates with septic shock. METHODS: This was a single-center prospective cohort study in a tertiary care hospital's level III neonatal intensive care unit. Neonates with septic shock and those who received noradrenaline as a first-line vasoactive agent were included. Clinical and hemodynamic parameters were recorded before and after one hour of noradrenaline infusion. The primary outcomes were: response at the end of one hour after starting noradrenaline infusion and mortality rate. RESULTS: A total of 21 babies were analyzed. The cohort comprised 17 preterm neonates. The mean age of presentation with septic shock was 74.3 h. Resolution of shock at one hour after starting noradrenaline was achieved in 76.2% of cases. The median duration of hospital stay was 14 days. The mean blood pressure improved after the initiation of noradrenaline from 30.6 mm of Hg [standard deviation (SD) 6.1] to 37.8 mm of Hg (SD 8.22, p < 0.001). Fractional shortening improved after noradrenaline initiation from 29% (SD 13.5) to 45.1% (SD 21.1, p < 0.001). The mortality rate was 28.6% in our study. CONCLUSION: Noradrenaline is a potential drug for use in neonatal septic shock, with improvement in mean blood pressure and fractional shortening; however, further studies with larger sample sizes are needed to confirm our findings before it can be recommended as first-line therapy in neonatal septic shock.

Neonatal sepsis is one of the leading causes of neonatal mortality. In neonates with septic shock, mortality is high at 35.4% in low- and middle-income countries. The evidence of the hemodynamic effects of noradrenaline in neonates is still sparse, so we carried out a study in our tertiary care neonatal intensive care unit to evaluate the effects of noradrenaline in neonates with septic shock. Neonates with septic shock and those who received noradrenaline as a first-line vasoactive agent were included. Clinical and hemodynamic parameters were recorded before and after one hour of noradrenaline infusion. The primary outcomes were: response at the end of one hour after starting noradrenaline infusion and mortality rate. A total of 21 babies were analyzed. We found that there was a statistically significant improvement in the mean blood pressure and fractional shortening after noradrenaline initiation. The mortality rate was 28.6% in our study. We conclude that noradrenaline is a relatively safe and effective drug for the treatment of neonatal septic shock. However, further studies with larger sample sizes are needed to confirm our findings before it can be recommended as first-line therapy in neonatal septic shock.

Effect of prehospital high-dose glucocorticoid on hemodynamics in patients resuscitated from out-of-hospital cardiac arrest: a sub-study of the STEROHCA trial.

BACKGROUND: Following resuscitated out-of-hospital cardiac arrest (OHCA), inflammatory markers are significantly elevated and associated with hemodynamic instability and organ dysfunction. Vasopressor support is recommended to maintain a mean arterial pressure (MAP) above 65 mmHg. Glucocorticoids have anti-inflammatory effects and may lower the need for vasopressors. This study aimed to assess the hemodynamic effects of prehospital high-dose glucocorticoid treatment in resuscitated comatose OHCA patients. METHODS: The STEROHCA trial was a randomized, placebo-controlled, phase 2 trial comparing one prehospital injection of methylprednisolone 250 mg with placebo immediately after resuscitated OHCA. In this sub-study, we included patients who remained comatose at admission and survived until intensive care unit (ICU) admission. The primary outcome was cumulated norepinephrine use from ICU admission until 48 h reported as mcg/kg/min. Secondary outcomes included hemodynamic status characterized by MAP, heart rate, vasoactive-inotropic score (VIS), and the VIS/MAP-ratio as well as cardiac function assessed by pulmonary artery catheter measurements. Linear mixed-model analyses were performed to evaluate mean differences between treatment groups at all follow-up times. RESULTS: A total of 114 comatose OHCA patients were included (glucocorticoid: n = 56, placebo: n = 58) in the sub-study. There were no differences in outcomes at ICU admission. From the time of ICU admission up to 48 h post-admission, patients in the glucocorticoid group cumulated a lower norepinephrine use (mean difference - 0.04 mcg/kg/min, 95% CI - 0.07 to - 0.01, p = 0.02). Moreover, after 12-24 h post-admission, the glucocorticoid group demonstrated a higher MAP with mean differences ranging from 6 to 7 mmHg (95% CIs from 1 to 12), a lower VIS (mean differences from - 4.2 to - 3.8, 95% CIs from - 8.1 to 0.3), and a lower VIS/MAP ratio (mean differences from - 0.10 to - 0.07, 95% CIs from - 0.16 to - 0.01), while there were no major differences in heart rate (mean differences from - 4 to - 3, 95% CIs from - 11 to 3). These treatment differences between groups were also present 30-48 h post-admission but to a smaller extent and with increased statistical uncertainty. No differences were found in pulmonary artery catheter measurements between groups. CONCLUSIONS: Prehospital treatment with high-dose glucocorticoid was associated with reduced norepinephrine use in resuscitated OHCA patients. TRIAL REGISTRATION: EudraCT number: 2020-000855-11; submitted March 30, 2020. URL: https://www. CLINICALTRIALS: gov ; Unique Identifier: NCT04624776.

Adverse Clinical Effects Associated With Non-catecholamine Pharmacologic Agents for Treatment of Vasoplegic Syndrome in Adult Cardiac Surgery.

Vasoplegic syndrome is a relatively common complication that can happen during and after major adult cardiac surgery. It is associated with a higher rate of complications, including postoperative renal failure, longer duration of mechanical ventilation, and intensive care unit stay, as well as increased mortality. The underlying pathophysiology of vasoplegic syndrome is that of profound vascular hyporesponsiveness, and involves a complex interplay among inflammatory cytokines, cellular surface receptors, and nitric oxide (NO) production. The pharmacotherapy approaches for the treatment of vasoplegia include medications that increase vascular smooth muscle contraction via increasing cytosolic calcium in myocytes, reduce the vascular effects of NO and inflammation, and increase the biosynthesis of and vascular response to norepinephrine. Clinical trials have demonstrated the clinical efficacy of non-catecholamine pharmacologic agents in the treatment of vasoplegic syndrome. With an increase in their use today, it is important for clinicians to understand the adverse clinical outcomes and patient risk profiles associated with these agents, which will allow better-tailored medical therapy.

Effect of norepinephrine, vasopressin, and dopamine for survivals of the elderly with sepsis and pre-existing heart failure.

Our study focused on evaluating the effect of three common vasoactive drugs on the prognosis of elderly patients with sepsis and pre-existing heart failure. The Medical Information Mart for Intensive Care III database, Version 1.4, was used. Our study included critically ill older patients (aged ≥ 65 years) with sepsis and heart failure treated with vasoactive drugs. Patients were divided into norepinephrine group, norepinephrine combined with vasopressin group, and dopamine group. The baseline characteristics, primary outcome, and secondary outcome measures were compared among the three groups. In total, 1357 elderly patients were included (766 in norepinephrine group, 250 in norepinephrine combined with vasopressin group, and 341 in dopamine group). After propensity score matching, statistically significant differences in 28-d and 90-d mortality (P = 0.046, P = 0.031) were observed; meanwhile, there was a significant difference in the incidence of mechanical ventilation, AKI, and malignant arrhythmias. Cox regression analysis revealed that norepinephrine combined with vasopressin decreased 5-year survival statistically(P = 0.001). Multiple linear regression analysis indicated dopamine as an independent risk factor in reducing ICU and hospital length of stay (P = 0.001, P = 0.017). Logistic regression analysis showed dopamine was an independent risk factor for new-onset arrhythmias (P < 0.001), while norepinephrine combined with vasopressin was an independent risk factor for new-onset malignant arrhythmias (P < 0.001). Norepinephrine in combination with vasopressin decreased survival and increased the incidence of malignant arrhythmias in elderly sepsis patients with pre-existing heart failure. Dopamine alone reduces ICU and hospital length of stay but increases the new-onset arrhythmias.

Position Paper on the Reporting of Norepinephrine Formulations in Critical Care from the Society of Critical Care Medicine and European Society of Intensive Care Medicine Joint Task Force.

OBJECTIVES: To provide guidance on the reporting of norepinephrine formulation labeling, reporting in publications, and use in clinical practice. DESIGN: Review and task force position statements with necessary guidance. SETTING: A series of group conference calls were conducted from August 2023 to October 2023, along with a review of the available evidence and scope of the problem. SUBJECTS: A task force of multinational and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. INTERVENTIONS: The implications of a variation in norepinephrine labeled as conjugated salt (i.e., bitartrate or tartrate) or base drug in terms of effective concentration of norepinephrine were examined, and guidance was provided. MEASUREMENTS AND MAIN RESULTS: There were significant implications for clinical care, dose calculations for enrollment in clinical trials, and results of datasets reporting maximal norepinephrine equivalents. These differences were especially important in the setting of collaborative efforts across countries with reported differences. CONCLUSIONS: A joint task force position statement was created outlining the scope of norepinephrine-dose formulation variations, and implications for research, patient safety, and clinical care. The task force advocated for a uniform norepinephrine-base formulation for global use, and offered advice aimed at appropriate stakeholders.

Donor noradrenaline use is associated with better allograft survival in recipients of pancreas transplantation.

INTRODUCTION: Outcomes following pancreas transplantation are suboptimal and better donor selection is required to improve this. Vasoactive drugs (VaD) are commonly used to correct the abnormal haemodynamics of organ donors in intensive care units. VaDs can differentially affect insulin secretion positively (dobutamine) or negatively (noradrenaline). The hypothesis was that some VaDs might induce beta-cell stress or rest and therefore impact pancreas transplant outcomes. The aim of the study was to assess relationships between VaD use and pancreas transplant graft survival. METHODS: Data from the UK Transplant Registry on all pancreas transplants performed between 2004 and 2016 with complete follow-up data were included. Univariable- and multivariable-adjusted Cox regression analyses determined risks of graft failure associated with VaD use. RESULTS: In 2,183 pancreas transplants, VaDs were used in the following numbers of donors: dobutamine 76 (3.5%), dopamine 84 (3.8%), adrenaline 161 (7.4%), noradrenaline 1,589 (72.8%) and vasopressin 1,219 (55.8%). In multivariable models, adjusted for covariates and the co-administration of other VaDs, noradrenaline use (vs non-use) was a strong predictor of better graft survival (hazard ratio [95% confidence interval] 0.77 [0.64-0.94], p = 0.01). CONCLUSIONS: Noradrenaline use was associated with better graft survival in models adjusted for donor and recipient variables - this may be related to inhibition of pancreatic insulin secretion initiating pancreatic beta-cell 'rest'. Further research is required to replicate these findings and establish whether relationships are causal. Identification of alternative methods of inducing beta-cell rest could be valuable in improving graft outcomes.

Effect of Early Administration of Vasopressin on New-Onset Arrhythmia Development in Patients With Septic Shock: A Retrospective, Observational Cohort Study.

Background: Adjunctive vasopressin use in septic shock reduces catecholamine requirements and is associated with a lower incidence of new-onset arrhythmias (NOAs). The association of vasopressin timing on NOA development is ill-described. Objective: To determine whether early administration of vasopressin was associated with a lower incidence of NOA in septic shock patients. Methods: A retrospective analysis of intensive care unit (ICU) patients at a large, academic medical center. Septic shock patients who required vasopressin and norepinephrine were eligible for inclusion. Patients were excluded for receipt of other vasoactive agents, history of cardiac arrhythmias, or outside hospital admission. Early vasopressin was defined as receipt within 6 hours of septic shock onset. The primary outcome was incidence of NOA. Results: In total, 436 patients, 220 (50.4%) in the early and 216 (49.6%) in the late vasopressin group, were included. Early vasopressin was not associated with a lower incidence of NOA compared with late vasopressin (9% vs 7%, median absolute difference [95% confidence interval, CI]: -2.1 [-7.2, 3.0], P = 0.41). Early vasopressin patients were observed to have shorter shock duration (2 vs 4 days, median absolute difference [95% CI]: 2 [1, 2], P < 0.001), and ICU length of stay (6 vs 7 days, median absolute difference [95% CI]: 1 [0, 2], P = 0.02). Conclusions and Relevance: Early vasopressin use was not associated with a lower incidence of NOA. Additional studies are needed to elucidate the effect of vasopressin timing on NOA and other clinical outcomes.

Does Early Vasopressin in Septic Shock Improve Outcomes? An Important Piece to This Emerging Puzzle Has Arrived.

In this month's Annals of Pharmacotherapy, the largest observational study assessing the early versus later use of vasopressin has been published. When this new study is combined with the other available observational studies, there are 2 important outcomes to focus on. When all the observational studies are pooled together, no reduction in new onset arrhythmias is seen (odds ratio [OR] = 0.91, 95% confidence interval [CI] = 0.41-1.95) with early versus late vasopressin use while the reduction in renal replacement therapy just missed statistical significance (OR = 0.56, 95% CI = 0.32-1.00). Early vasopressin likely does not reduce new onset arrhythmias versus later use but might reduce the need for renal replacement therapy.

Albumin use in patients with septic shock-Post-hoc analyses of an international randomised fluid trial.

BACKGROUND: Albumin administration is suggested in patients with sepsis and septic shock who have received large volumes of crystalloids. Given lack of firm evidence, clinical practice variation may exist. To address this, we investigated if patient characteristics or trial site were associated with albumin use in septic shock. METHODS: We conducted a post-hoc study of the CLASSIC international, randomised clinical trial of fluid volumes in septic shock. Associations between selected baseline variables and trial site with albumin use during ICU stay were assessed in Cox models considering death, ICU discharge, and loss-to-follow-up as competing events. Baseline variables were first assessed individually, adjusted for treatment allocation (restrictive vs. standard IV fluid), and then adjusted for allocation and the other baseline variables. Site was assessed in a model adjusted for allocation and baseline variables. RESULTS: We analysed 1541 of 1554 patients randomised in CLASSIC (99.2%). During ICU stay, 36.3% of patients in the restrictive-fluid group and 52.6% in the standard-fluid group received albumin. Gastrointestinal focus of infection and higher doses of norepinephrine were most strongly associated with albumin use (subgroup with highest quartile of norepinephrine doses, hazard ratio (HR) 2.58, 95% CI 1.89 to 3.53). HRs for associations between site and albumin use ranged from 0.11 (95% CI 0.05 to 0.26) to 1.70 (95% CI 1.06 to 2.74); test for overall effect of site: p < .001. CONCLUSIONS: In adults with septic shock, gastrointestinal focus of infection and higher doses of norepinephrine at baseline were associated with albumin use, which also varied substantially between sites.

Exploring the norepinephrine to angiotensin II conversion ratio in patients with vasodilatory hypotension: A post-hoc analysis of the ARAMIS trial.

PURPOSE: Angiotensin II is approved for catecholamine-refractory vasodilatory shock but the conversion dose ratio from norepinephrine to angiotensin II remains unclear. METHODS: We conducted a post-hoc analysis of the Acute Renal effects of Angiotensin II Management in Shock (ARAMIS) trial involving patients with vasodilatory hypotension. We determined the norepinephrine equivalent dose immediately prior to angiotensin II initiation and calculated the conversion dose ratio between norepinephrine and angiotensin II. We performed subgroup analyses based on recent exposure to angiotensin receptor blockers (ARBs) and renin levels at baseline. RESULTS: In 37 patients, the median conversion dose ratio between norepinephrine equivalent and angiotensin II was to 10:1 for norepinephrine bitartrate (5:1 for norepinephrine base). The conversion ratio was not affected by the baseline renin, with a median ratio of 10 (7-21) in the high renin group versus 12 (5-22) in the low renin group. Finally, exposure to ARBs prior admission appeared to diminish the conversion ratio with a median ratio of 7 (4-13) in ARB patients vs. 12 (7-22) in non-ARB patients. CONCLUSIONS: The norepinephrine to angiotensin II conversion dose ratio is 10:1 in a vasodilatory hypotension population. These findings can guide clinicians and researchers in the use, dosing, and study of angiotensin II in critical care.

Norepinephrine versus epinephrine for hemodynamic support in post-cardiac arrest shock: A systematic review.

PURPOSE: The preferred vasopressor in post-cardiac arrest shock has not been established with robust clinical outcomes data. Our goal was to perform a systematic review and meta-analysis comparing rates of in-hospital mortality, refractory shock, and hemodynamic parameters in post-cardiac arrest patients who received either norepinephrine or epinephrine as primary vasopressor support. METHODS: We conducted a search of PubMed, Cochrane Library, and CINAHL from 2000 to 2022. Included studies were prospective, retrospective, or published abstracts comparing norepinephrine and epinephrine in adults with post-cardiac arrest shock or with cardiogenic shock and extractable post-cardiac arrest data. The primary outcome of interest was in-hospital mortality. Other outcomes included incidence of arrhythmias or refractory shock. RESULTS: The database search returned 2646 studies. Two studies involving 853 participants were included in the systematic review. The proposed meta-analysis was deferred due to low yield. Crude incidence of in-hospital mortality was numerically higher in the epinephrine group compared with norepinephrine in both studies, but only statistically significant in one. Risk of bias was moderate to severe for in-hospital mortality. Additional outcomes were reported differently between studies, minimizing direct comparison. CONCLUSION: The vasopressor with the best mortality and hemodynamic outcomes in post-cardiac arrest shock remains unclear. Randomized studies are crucial to remedy this.

Impact of blood pressure targets on central hemodynamics during intensive care after out-of-hospital cardiac arrest.

OBJECTIVES: The aim was to investigate the advanced hemodynamic effects of the two MAP-targets during intensive care on systemic hemodynamics in comatose patients after cardiac arrest. DESIGN: Secondary analysis of a randomized controlled trial. SETTING: Primary vasopressor used was per protocol norepinephrine. Hemodynamic monitoring was done with pulmonary artery catheters (PAC) and measurements were made on predefined time points. The primary endpoint of this substudy was the difference in cardiac index within 48 h from a repeated measurements-mixed model. Secondary endpoints included systemic vascular resistance index (SVRI), heart rate, and stroke volume index. PATIENTS: Comatose survivors after out-of-hospital cardiac arrest. INTERVENTIONS: The "Blood pressure and oxygenations targets after out-of-hospital cardiac arrest (BOX)"-trial was a randomized, controlled, double-blinded, multicenter-study comparing targeted mean arterial pressure (MAP) of 63 mmHg (MAP63) vs 77 mmHg (MAP77). MEASUREMENTS AND MAIN RESULTS: Among 789 randomized patients, 730 (93%) patients were included in the hemodynamic substudy. From PAC-insertion (median 1 hours after ICU-admission) and the next 48 hours, the MAP77-group received significantly higher doses of norepinephrine (mean difference 0.09 µg/kg/min, 95% confidence interval (CI) 0.07-0.11, pgroup < 0.0001). Cardiac index was significantly increased (0.20 L/min/m2 (CI 0.12-0.28), pgroup < 0.0001) as was SVRI with an overall difference of (43 dynes m2/s/cm5 (CI 7-79); pgroup = 0.02). Heart rate was increased in the MAP77-group (4 beats/minute; CI 2-6, pgroup < 0.003), but stroke volume index was not (pgroup = 0.10). CONCLUSIONS: Targeted MAP at 77 mmHg compared to 63 mmHg resulted in a higher dose of norepinephrine, increased cardiac index and SVRI. Heart rate was also increased, but stroke volume index was not affected by a higher blood pressure target.

Risk of arrhythmia in post-resuscitative shock after out-of-hospital cardiac arrest with epinephrine versus norepinephrine.

OBJECTIVE: To determine the rates of clinically significant tachyarrhythmias and mortality in the management of post-resuscitative shock after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA) who receive a continuous epinephrine versus norepinephrine infusion. DESIGN: Retrospective cohort study. SETTING: A large multi-site health system with hospitals across the United States. PATIENTS: Adult patients admitted for OHCA with post-resuscitative shock managed with either epinephrine or norepinephrine infusions within 6 h of ROSC. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Between May 5th, 2018, to January 31st, 2022, there were 221 patients admitted for OHCA who received post-resuscitative epinephrine or norepinephrine infusions. There was no difference in the rate of tachyarrhythmias between epinephrine and norepinephrine infusion in univariate (47.1% vs 41.7%, OR 1.24, 95% CI 0.71-2.20) or multivariable analysis (OR 1.34, 95% CI 0.68-2.62). Patients treated with epinephrine were more likely to die during hospitalization than those treated with norepinephrine (90.0% vs 54.3%, OR 6.21, 95% CI 2.37-16.25, p < 0.001). Epinephrine treated patients were more likely to have re-arrest during hospital admission (55.7% vs 14.6%, OR 5.77, 95% CI 2.74-12.18, p < 0.001). CONCLUSION: There was no statistically significant difference in clinically significant cardiac tachyarrhythmias in post-OHCA patients treated with epinephrine versus norepinephrine infusions after ROSC. Re-arrest rates and in-hospital mortality were higher in patients who received epinephrine infusions in the first 6 h post-ROSC. Results of this study add to the literature suggesting norepinephrine may be the vasopressor of choice in post-OHCA patients with post-resuscitative shock after ROSC.