Duration Of Vasopressor Use Research Articles

The relationship between dexmedetomidine administration and prognosis in patients with sepsis-induced coagulopathy: a retrospective cohort study.

Background: This study aimed to investigate whether dexmedetomidine provides survival benefit in critically ill patients with sepsis-induced coagulopathy (SIC). Methods: Patients with sepsis-induced coagulopathy admitted to the ICU were identified from the Medical Information Marketplace for Intensive Care (MIMIC)-IV database. They were divided into two groups: patients who started dexmedetomidine within 48h of ICU admission and lasted for more than 4h and patients who did not receive dexmedetomidine as a control group. The primary outcome was 28-day hospital mortality, the secondary outcome was in-hospital mortality, and the extended outcomes included duration of mechanical ventilation and vasopressor use, ICU stay, and hospital stay. Propensity score matching (PSM) analysis was used to match patients who received dexmedetomidine with those who did not, and multivariable Cox models and logistics models were used to account for baseline differences and unmeasured confounders. An external validation was performed with the Critical care database comprising patients with infection at Zigong Fourth People's Hospital. Results: After PSM, 592 patients who received dexmedetomidine were matched with 592 patients who did not receive dexmedetomidine. In the primary and secondary endpoints, dexmedetomidine was associated with a lower risk of 28-day hospital mortality (19.3% vs. 14.2%, hazard ratio (HR) 0.71; P = 0.020) and in-hospital mortality (22.3% vs. 16.4%, odds ratio (OR) 0.68; P = 0.017) in patients with SIC. Regarding the extended outcome, dexmedetomidine was also associated with a longer length of hospital stay (median 12.54days vs. 14.87days, P = 0.002) and longer ICU stay (median 5.10days vs. 6.22days, P = 0.009). In addition, the duration of mechanical ventilation was significantly increased in the dexmedetomidine group (median 41.62h vs. 48.00h, p = 0.022), while the duration of vasopressor use was not significantly different (median 36.67h vs. 39.25h, p = 0.194). Within 48h of ICU stay, receiving a dose of dexmedetomidine greater than 0.474μg/kg/h and continuous dexmedetomidine administration for 24-48h may be associated with 28-day hospitalization outcomes in patients with SIC. External cohort validation also found that the use of dexmedetomidine after admission to the ICU can reduce 28-day mortality in patients with SIC. Conclusion: Dexmedetomidine administration is associated with reduced 28-day hospital mortality and in-hospital mortality in critically ill patients with SIC, and these findings deserve further verification in randomized controlled trials.

Effectiveness and safety of Shenfu injection in septic patients with hypoperfusion: A multi-center, open-label, randomized, controlled trial

BackgroundTo evaluate the effectiveness and safety of the Shenfu injection (SFI) combined with standard bundle treatment in septic patients with hypoperfusion. MethodThis study was a multi-center, randomized, open-label, controlled trial conducted in four teaching hospitals in China. The septic patients with hypoperfusion and traditional Chinese medicine (TCM) syndrome with Yang-Qi deficiency were enrolled from January 2019, through September 2020. Eligible patients were randomly allocated in a 1:1 ratio to either receive 60 mL of SFI infusion per day plus standard treatment (SFI group) or standard bundle treatment alone (control group). The primary outcome was 28-day all-cause mortality. Secondary outcomes were 90-day all-cause mortality time to weaning from mechanical ventilation, time to weaning from vasopressors, time to discharge from the ICU and hospital, and laboratory results after randomization. ResultsA total of 188 patients completed the trail. This study revealed that the results of the SFI group and the control groups were not statistically significant in 28-day all-cause mortality (10.6% vs. 20.2%, respectively; P=0.106). The infusion of SFI was associated with a significant reduction in the duration of vasopressor use (median=4.0 days, interquartile range [IQR]: 2.0 days–6.0 days vs. median=5.0 days, IQR: 3.0 days–8.0 days, respectively; P=0.043). Patients in the SFI group had statistically greater reductions in plasma lactate levels compared with those in the control group at the first 12 h (median=1.1 mmol/L, IQR: 0.3–2.0 mmol/L vs. median=0.0 mmol/L, IQR: −0.2 to 0.8 mmol/L, respectively; P <0.001) and 24 h (median=1.4 mmol/L, IQR: 0.3–2.2 mmol/L vs. median=0.4 mmol/L, IQR: −0.4 to 1.6 mmol/L, respectively; P=0.001). ConclusionSFI plus standard therapy did not significantly decrease 28-day all-cause mortality for septic patients with hypoperfusion and TCM syndrome with Yang-Qi deficiency.Trial registration Chinese Clinical Trial Registry Identifier: ChiCTR1800020435

The effects of vitamin C supplementation in the critically ill patients outcomes: A systematic review and meta-analysis of randomized controlled trials.

Vitamin C has significant anti-inflammatory effects and is particularly important for critically ill patients. However due to inconsistent research findings in critically ill patients in meta-analysis. Therefore, the primary objective of this meta-analysis is to investigate the effects of isolated intravenous supplementation of vitamin C in adults with critical illness by comprehensively incorporating articles from randomized controlled trials. Articles included searching through PubMed, Embase, Medline, Cochrane Library, and Web of Science up to April 28, 2023, for articles on vitamin C and the critically ill. We calculated pooled standard relative risk (RR), mean difference (MD), and 95% confidence intervals (CIs). And the protocol for the review has been registered on PROSPERO (CRD42023425193). There are 2047 critically ill included in 19 articles. Compared with placebo, patients who underwent intravenous vitamin C (IVVC) have reduced duration of vasopressor used (SMD 0.26; CI 0.01-0.51; I2 = 87.0%, P = .044), mechanical ventilation (SMD -0.29; CI -0.55 to -0.03; I2 = 36.8%, P = .031). However, the administration of IVVC had no statistical difference in 28-d mortality (RR 0.95; CI 0.80-1.11; I2 = 12.2%, P = .337), mortality (RR 0.79; CI 0.55-1.12; I2 = 0%, P = .188), fluid intake (SMD -0.02; CI -0.25 to 0.20; I2 = 0%, P = .838), urine output (SMD 0.23; CI -0.03 to 0.49; I2 = 0%, P = .084), ICU days (SMD 0.10; CI -0.03 to 0.22; I2 = 0%, P = .127), hospital stay (SMD 0.10; CI -0.12 to 0.32; I2 = 0%, P = .375), and pneumonia (RR 0.85; CI 0.50-1.44; I2 = 0%, P = .552). This study comprehensively and systematically evaluated IVVC supplementation in the critically ill through a meta-analysis of RCT. There is no difference except for patients who had reduced duration of vasopressor use and mechanical ventilation by the administration of IVVC. Of course. More scientific and rigorous conclusions can be drawn from multi-center RCT research in the future.

Cluster analysis driven by unsupervised latent feature learning of medications to identify novel pharmacophenotypes of critically ill patients

Unsupervised clustering of intensive care unit (ICU) medications may identify unique medication clusters (i.e., pharmacophenotypes) in critically ill adults. We performed an unsupervised analysis with Restricted Boltzmann Machine of 991 medications profiles of patients managed in the ICU to explore pharmacophenotypes that correlated with ICU complications (e.g., mechanical ventilation) and patient-centered outcomes (e.g., length of stay, mortality). Six unique pharmacophenotypes were observed, with unique medication profiles and clinically relevant differences in ICU complications and patient-centered outcomes. While pharmacophenotypes 2 and 4 had no statistically significant difference in ICU length of stay, duration of mechanical ventilation, or duration of vasopressor use, their mortality differed significantly (9.0% vs. 21.9%, p < 0.0001). Pharmacophenotype 4 had a mortality rate of 21.9%, compared with the rest of the pharmacophenotypes ranging from 2.5 to 9%. Phenotyping approaches have shown promise in classifying the heterogenous syndromes of critical illness to predict treatment response and guide clinical decision support systems but have never included comprehensive medication information. This first-ever machine learning approach revealed differences among empirically-derived subgroups of ICU patients that are not typically revealed by traditional classifiers. Identification of pharmacophenotypes may enable enhanced decision making to optimize treatment decisions.

The effect of vitamin C in adults with sepsis: a meta-analysis of randomized controlled trials.

The effect of intravenous (IV) vitamin C in the treatment of sepsis remains controversial. We aimed to explore the clinical efficacy of vitamin C in the treatment of sepsis. Electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) were searched from inception through November 15th, 2022, for randomized controlled trials evaluating the effect of IV vitamin C treatment in patients with sepsis. The primary outcome was short-term mortality, secondary outcomes included duration of vasopressor use, length of intensive care unit (ICU) stay, and Sequential Organ Failure Assessment (SOFA) score after vitamin C treatment. Subgroup analyses were performed based on the dose and duration of IV vitamin C and region to determine whether vitamin C benefited patients with sepsis. A total of 10 studies including 1,426 patients fulfilled the predefined criteria and were analyzed. Overall, there were no significant differences between the vitamin C group and the control group regarding short-term mortality [odds ratio (OR), 0.61; 95% confidence interval (CI) 0.37-1.01; p = 0.05], ICU length of stay [mean difference (MD), -1.24; 95% CI -3.54 to 1.05, p = 0.29] and SOFA score (MD, -0.85, 95% CI -2.38 to 0.67, p = 0.27). However, vitamin C significantly reduced the duration of vasopressor use (MD, -14.36, 95% CI -26.11 to -2.61, p = 0.02). Furthermore, subgroup analysis found that in developing countries, vitamin C was associated with a significant reduction in short-term mortality (OR, 0.33; 95% CI 0.12-0.90; p = 0.03), duration of vasopressor use (MD, -24.37, 95% CI -33.72 to -15.02, p < 0.001) and SOFA score (MD, -2.55, 95% CI -4.81 to -0.28, p = 0.03). In our study, vitamin C administration for sepsis patients was not associated with a significant reduction in short-term mortality, length of ICU stay or SOFA score. However, we observed that vitamin C could reduce the duration of vasopressor use. Furthermore, sepsis patients in developing countries may benefit more from vitamin C administration than those in developed countries.Systematic review registration: Identifier CRD42022380958, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=380958.

Treatment Modalities in Calcium Channel Blocker Overdose: A Systematic Review.

Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified approach for treating these patients in the existing literature. This study aimed to assess the effects of different treatment modalities used in calcium channel blocker poisoning, as reported by previous studies. The primary outcomes studied were mortality and hemodynamic parameters after treatment. The secondary outcomes were the length of hospital stay, length of intensive care unit stay, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. A thorough literature search was performed through Ovid, PubMed, Cochrane Library, and Google Scholar from January 2014 to December 31, 2022, to identify all studies analyzing the effects of the treatment of calcium channel blocker poisoning on the desired outcomes. Two reviewers reviewed 607 published articles from January 2014 to December 2022 to identify studies analyzing the effects of the treatment of calcium channel blocker poisoning on desired outcomes. In this review, 18 case reports, one case series, and one cohort study were included. Most patients were treated with an injection of calcium gluconate or calcium chloride. The use of calcium along with dopamine and norepinephrine was found to have lower mortality rates. A few patients were also treated with injection atropine for bradycardia. High-dose insulin therapy was used in 14 patients, of whom two did not survive. In the cohort study, 66 calcium channel blocker toxicity patients were included. These patients were treated with high-dose insulin therapy. A total of 11 patients with calcium channel blocker toxicity succumbed. Although it was found to be associated with improved hemodynamic parameters and lower mortality, side effects such as hypokalemia and hypoglycemia were noted. Intravenous lipid emulsion therapy (administered to eight patients), extracorporeal life support (used in three patients with refractory shock or cardiac arrest), injection glucagon, methylene blue, albumin infusion, and terlipressin were associated with a lower mortality rate as well as improvement in hemodynamic parameters. None of the case reports provided any information on end-organ damage on long-term follow-up.

The outcome of IV vitamin C therapy in patients with sepsis or septic shock: a meta-analysis of randomized controlled trials

BackgroundTo update a meta-analysis of randomized controlled trials (RCTs) and further explore the outcome of IV vitamin C (IVVC) administration in sepsis or septic shock patients.MethodsThis study is a meta-analysis of RCTs. The RCTs of vitamin C therapy in sepsis or septic shock were searched in PubMed, EMBASE and Clinical Trials.gov from inception to January 16, 2023. We registered the protocol with PROSPERO (CRD42022354875). The primary outcome was delta Sequential Organ Failure Assessment (SOFA) score at 72–96 h. Two reviewers independently assessed RCTs according to eligibility criteria: (1) study type: RCT; (2) patient population: patients ≥ 18 years with sepsis or septic shock; (3) intervention: IVVC at any doses as monotherapy or combined with thiamine or and hydrocortisone compared with standard of care, no intervention or placebo (defined as control group); (4) the RCT described short-term mortality or SOFA score. Then, two authors independently extracted related information from RCTs.ResultsEighteen RCTs (n = 3364 patients) were identified in this meta-analysis. There were significant effects in the delta SOFA score from baseline to 72–96 h (MD, − 0.62; 95% CI, − 1.00 to − 0.25; p = 0.001) and the duration of vasopressor use (MD, − 15.07; 95% CI, − 21.59 to − 8.55; p < 0.00001) with IVVC therapy. Treatment with IVVC was not shown to improve short-term mortality (OR, 0.89; 95% CI, 0.77 to 1.04; p = 0.14); nevertheless, dose at 25–100 mg/kg/d subgroup associated with a significant reduction in short-term mortality (OR, 0.80; 95% CI, 0.65 to 0.97; p = 0.03). An increase adverse event was observed in IVVC therapy (OR, 1.98; 95% CI, 1.06 to 3.68; p = 0.03).ConclusionIn this meta-analysis, IVVC in sepsis or septic shock patients significantly improved delta SOFA score and reduced the duration of vasopressor use, whereas it was not associated with reduction in short-term mortality and had higher adverse events.

Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial.

The main purpose of our research was to further clarify the effectiveness and potential pathophysiological principles of metabolic resuscitation therapy in critically ill patients with sepsis and septic shock. We found that metabolic resuscitation therapy is beneficial for patients with sepsis and septic shock, shortening the length of intensive care unit (ICU) stay, reducing the duration of vasopressor use, and reducing the ICU mortality rate of patients with sepsis and septic shock, but it does not reduce the hospital mortality rate.

Annals for Hospitalists - February 2023

Annals for Hospitalists - February 2023

Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension

BackgroundIntravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited.MethodsIn an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that all-cause mortality before discharge home by day 90 (primary outcome) would be lower with a restrictive fluid strategy than with a liberal fluid strategy. Safety was also assessed.ResultsA total of 1563 patients were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Resuscitation therapies that were administered during the 24-hour protocol period differed between the two groups; less intravenous fluid was administered in the restrictive fluid group than in the liberal fluid group (difference of medians, −2134 ml; 95% confidence interval [CI], −2318 to −1949), whereas the restrictive fluid group had earlier, more prevalent, and longer duration of vasopressor use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference, −0.9 percentage points; 95% CI, −4.4 to 2.6; P=0.61); 5 patients in the restrictive fluid group and 4 patients in the liberal fluid group had their data censored (lost to follow-up). The number of reported serious adverse events was similar in the two groups.ConclusionsAmong patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy. (Funded by the National Heart, Lung, and Blood Institute; CLOVERS ClinicalTrials.gov number, NCT03434028.)

Efficacy of Ascorbic Acid, Thiamine, and Hydrocortisone Combination Therapy: Meta-analysis of Randomized Controlled Trials.

Sepsis is a life-threatening biological condition that induces systemic tissue and organ dysfunction and confers a high mortality risk. Although the use of hydrocortisone in combination with ascorbic acid and thiamine (HAT therapy) significantly reduced mortality from sepsis or septic shock in a previous study, it did not improve mortality in subsequent randomized controlled trials (RCTs). Therefore, no definitive conclusion has been established on the benefits of HAT therapy for sepsis or septic shock. We performed a meta-analysis to assess the treatment outcomes of HAT therapy in patients with sepsis or septic shock. We searched databases (PubMed/MEDLINE, Embase, Scopus and Cochrane Library) for RCTs using the terms "ascorbic acid", "thiamine", "sepsis", "septic shock", and "RCT". The primary outcome of this meta-analysis was the mortality rate, and the secondary outcomes were the incidence of new-onset acute renal injury (AKI), intensive care unit (ICU) length of stay (ICU-LOS), change in the Sequential Organ Failure Assessment (SOFA) score within 72 hours, and duration of vasopressor use. Nine RCTs were identified and included in the outcome evaluation. HAT therapy did not improve the 28-day and ICU mortality, new-onset AKI, ICU-LOS, or SOFA scores. However, HAT therapy significantly shortened the duration of vasopressor use. HAT therapy did not improve mortality, the SOFA score, renal injury, or ICU-LOS. Further studies are needed to confirm whether it shortens the duration of vasopressor use.

A Systematic Review and Meta-Analysis on Possible Role of Vitamin C in Sepsis.

Sepsis is a substantial healthcare burden, and its management continues to be a major challenge. Prior studies demonstrate conflicting evidence regarding the utility of vitamin C in sepsis. This systematic review and meta-analysis aim to collect data among critically ill patients (sepsis/septic shock), comparing the efficacy of parenteral vitamin C with standard care. A literature review was conducted using databases including PubMed, Web of Science, Google Scholar, and the Cochrane Library to identify randomized controlled trials (RCTs) and observational studies comparing intravenous vitamin C alone or in combination with thiamine or glucocorticoids to the standard of care. We identified 11 RCTs and seven retrospective cohort studies. The primary outcome was 28-day mortality. Secondary outcomes included intensive care unit (ICU) length of stay, change inSequential Organ Failure Assessment (SOFA) score, duration of vasopressor use, and duration of mechanical ventilation. A total of 18 studies with 4078 patients were included in our final analysis. Overall, we found no mortality reduction in patients treated with vitamin C compared to standard of care (odds ratio (OR) 0.92; 95% confidence interval (CI) 0.78 to 1.09; p = 0.34). Studies that reported a change in SOFA scores, ICU length of stay, duration of mechanical ventilation, or duration of vasopressor use did not show any significant difference between groups. Subgroup analysis with RCT versus observational studies and vitamin C dosage regimens did not show any difference. Among patients with sepsis or septic shock, treatment with vitamin C was not associated with a reduction in mortality, ICU length of stay, change in SOFA score, duration of vasopressor use, or duration of mechanical ventilation. Further studies are needed to demonstrate the potential role of vitamin C in the management of sepsis.

Ultrasound dynamic monitoring of IVCD to guide application of CRRT in patients with renal failure combined with acute heart failure

We explored the application value of bedside ultrasound dynamic monitoring of the inferior vena cava diameter (IVCD) and collapse with sniff (inferior vena cava collapsibility index [IVCCI]) to guide dehydration adjustment in continuous renal replacement therapy (CRRT) in patients with combined renal failure and acute heart failure. We selected 90 patients with combined renal and acute heart failure who required CRRT in the intensive care unit (ICU) from January 2019 to June 2021. According to different blood volume assessment methods, patients were randomly divided into ultrasound, experience, and control groups. We compared serum creatinine, potassium, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels; time to improved heart failure symptoms; CRRT time; ventilator use; ICU length of stay; vasopressor use; and incidence of adverse events among groups. There were no significant differences in serum creatinine, potassium, and NT-proBNP levels in pairwise comparisons among groups before and after CRRT (P > 0.05). The time to improved heart failure symptoms, CRRT time, and ICU length of stay in the ultrasound and experience groups were lower than those in the control group; the differences were statistically significant (P < 0.05). Ventilator use duration was lower in the ultrasound and experience groups compared with the control group, with a statistically significant difference between the ultrasound and control groups (P < 0.05). The duration of vasopressor use in the ultrasound and control groups was lower than that in the experience group; the difference was statistically significant (P < 0.05). The incidence of adverse events was lower in the ultrasound group compared with the experience and control groups; the difference was statistically significant (P < 0.05). Ultrasound dynamic monitoring of IVCD and collapse with sniff can accurately assess blood volume status, and provide guidance for dehydration adjustments in CRRT and rapid relief of heart failure symptoms in patients with combined renal and acute heart failure.

No benefit of hydrocortisone, ascorbic acid, and thiamine in reducing mortality in adult sepsis patients: a systematic review and meta-analysis

Abstract Background Supplementation of corticosteroid, ascorbic acid and thiamine in adult septic patients remains controversial. We aimed to evaluate the efficacy and safety of hydrocortisone, ascorbic acid and thiamine (HAT) in adult septic patients. Methods Data search included Pumbed, EMBASE, and the Cochrane Library from inception to Sep, 2021. Only studies with classifications of sepsis and intravenous HAT treatment were included. Adult patients with sepsis (aged ≥18 years) were divided into 2 groups. The treatment group received HAT therapy, whereas the control group received standard care and/or intravenous hydrocortisone. The primary outcome was hospital mortality. Results Eleven studies including 4579 patients who fulfilled the predefined criteria were analyzed (6 randomized controlled trials [RCTs] and 5 clinical cohort studies). No hospital mortality reduction was demonstrated in patients treated with HAT when compared to the reference (OR: 0.99; 95% CI: 0.77 to 1.27; I 2 = 39%) group. Sequential organ failure assessment (SOFA) score decrement at 72hours was more significant in HAT-treated patients (mean difference [MD]: –1.23; 95% CI: –1.94 to –0.53; I 2 = 81%). There was no difference in the duration of vasopressor use between HAT-treated patients and controls (MD: –4.92; 95% CI: –24.38 to 14.53; I 2 = 97%). Statistical heterogeneity was noted with no sign of significant publication bias. Conclusion In adult sepsis and septic shock patients, HAT treatment failed to reduce mortality or shorten vasopressor duration, but reduced SOFA scores.

EFFECTS OF SHENFU INJECTION ON SUBLINGUAL MICROCIRCULATION IN SEPTIC SHOCK PATIENTS: A RANDOMIZED CONTROLLED TRIAL.

Background and Objective: The optimization of macrocirculatory hemodynamics is recommended by current sepsis guidelines. However, microcirculatory dysfunction is considered the cause of severe sepsis. In the present study, we designed to verify whether the application of Shenfu injection (SFI) restores microcirculation, thereby improving tissue perfusion and inhibiting organ dysfunction, resulting in improved outcomes. Design: We conducted a prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Intervention: Patients were randomly assigned to group receiving SFI (n = 20) or placebo (n = 20) for 5 days. We administered SFI or glucose injection for 5 days and blinded the investigators and clinical staff by applying light-proof infusion equipment that concealed therapy allocation. Measurements and Results: We measured the systemic dynamics and lactate levels, biomarkers of endothelial dysfunction, and inflammatory cytokines in the plasma. The parameters of sublingual microcirculation were assessed using side-stream dark-field imaging. Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation (APACHE) score, total dose, and duration of vasopressor use, emergency intensive care unit (EICU) stay, and 28-day mortality were evaluated. After treatment with SFI, the disturbance of the sublingual microcirculation was considerably alleviated, as indicated by the significant increase in total vessel density, perfused vessel density, and microvascular flow index. Moreover, the plasma biomarker levels of endothelial dysfunction, including Ang-2, Syn-1, and ET-1, were reversed after SFI treatment. Importantly, the SFI group had a more favorable prognosis than the control group in terms of the APACHE-II score, SOFA score, duration of vasopressor administration, and length of EICU stay. However, the difference in mortality at day 28 was not statistically different between the SFI (15%, 3/20) and placebo (25%, 5/20) groups ( P = 0.693). Conclusions : Shenfu injection provided apparent effects in improving sublingual microcirculatory perfusion in patients with septic shock, and this protection may be related with the inhibition of endothelial dysfunction and vasodilatory effects.

Efficacy and safety of metaraminol in critically ill patients with shock: a systematic review

AbstractAimTo assess the efficacy and safety of metaraminol infusions in comparison to other vasopressors in critically ill patients with shock with regard to hospital mortality, effect on haemodynamics (mean arterial pressure or systolic blood pressure), duration of vasopressor use, and adverse events.Data sourcesA systematic review was conducted in eight electronic databases and nine trial registers from inception to 17 March 2021.Study selectionStudies included randomised or non‐randomised controlled trials, and retrospective or prospective observational studies of critically ill adult patients admitted to the intensive care unit or emergency department with shock of any aetiology and who received metaraminol via continuous infusion compared to patients who received other vasopressors.ResultsOut of 1387 eligible articles, three observational studies and one controlled trial were included involving a total of 54 patients. Study patients had different types of shock including septic (n = 28), cardiogenic (n = 21), hypovolemic (n = 3) and neurogenic shock (n = 2). All studies compared metaraminol to noradrenaline and were of poor quality and high risk of bias. There was no difference in hospital mortality or effect on mean arterial pressure or systolic blood pressure between metaraminol and noradrenaline in any of the studies. None of the studies reported the duration of vasopressor use or adverse drug events such as extravasation or tissue injury.ConclusionThere is limited and low‐quality efficacy and safety data to support the use of metaraminol over other vasopressors in critically ill patients with shock. Future clinical trials are needed before this agent is routinely used in this patient population.

Association of Thiamine Use with Outcomes in Patients with Sepsis and Alcohol Use Disorder: An Analysis of the MIMIC-III Database.

IntroductionThe association between thiamine use and clinical outcomes among patients with sepsis and alcohol use disorder (AUD) is unclear.MethodsIn this retrospective cohort study of patients from Medical Information Mart for Intensive Care III (MIMIC-III, version 1.4), we evaluated the association of thiamine use with clinical outcomes in patients with AUD and sepsis. The primary outcome was 28-day survival, and secondary outcomes included ICU, in-hospital, and 90-day mortality, ICU and hospital length of stay, duration of vasopressor use, need and duration of continuous renal replacement therapy (CRRT), and dynamic changes for variables up to day 7 after ICU admission.ResultsA total of 944 patients with sepsis and AUD were included in this cohort [median age, 53.1 years; women, 26.0% (245 of 944)]. Among all patients, 24.6% (233 of 944) received thiamine with a dose of 200 mg (IQR 100–345 mg). The 28-day mortality was 11.2% (26 of 233) in the thiamine use group compared with 18.6% (132 of 711) in the no thiamine use group (P = 0.009). After adjustment for a series of confounders, the mixed-effects Cox proportional hazards models showed that administration of thiamine was associated with a lower risk of 28-day mortality compared with no administration of thiamine.ConclusionsIn critically ill patients with alcohol use disorder admitted for sepsis, treatment with thiamine may be associated with a decreased risk of death. However, the present results should be interpreted with caution due to the limitations of retrospective design. Additional larger, multicenter randomized controlled trials are needed to confirm our findings.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00603-1.

Effect of IV High-Dose Vitamin C on Mortality in Patients With Sepsis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials to investigate whether IV high-dose vitamin C improves the short-term mortality of patients with sepsis. This study is a systematic review and meta-analysis of randomized controlled trials. We searched EMBASE, the Cochrane Central Register of Controlled Trials, and MEDLINE for randomized controlled trials that met inclusion criteria. The protocol was registered at the University hospital Medical Information Network Clinical Trials Registry (UMIN000040528). All analyses were presented with the use of random-effects models. The primary outcome was short-term mortality defined as 28-day, 30-day, or in-hospital mortality. Two authors independently evaluated the following eligibility criteria: 1) randomized controlled trial, 2) patients with sepsis aged ≥18 years, and 3) received intravenous high-dose vitamin C in addition to standard of care, or standard of care alone. Then, two authors independently extracted the selected patient and study characteristics and outcomes from studies that met above eligibility criteria. Eleven randomized controlled trials (n = 1,737 patients) were included in this meta-analysis. High-dose IV vitamin C was not associated with a significantly lower short-term mortality (risk ratio, 0.88; 95% CI, 0.73-1.06; p = 0.18; I2 = 29%) but was associated with a significantly shorter duration of vasopressor use (standardized mean difference, -0.35; 95% CI, -0.63 to -0.07; p < 0.01; I2 = 80%) and a significantly greater decline in the Sequential Organ Failure Assessment score at 72-96 hours (standardized mean difference, -0.20; 95% CI, -0.32 to -0.08; p < 0.01; I2 = 16%). One study reported significant association with hypernatremia, but adverse effects were rare, and high-dose vitamin C is deemed relatively safe. In this meta-analysis, the use of IV high-dose vitamin C in patients with sepsis was not associated with lower short-term mortality although it was associated with significantly shorter duration of vasopressor use and greater decline in the Sequential Organ Failure Assessment score at 72-96 hours.

Early vs. Late Vassopressor therapy in the Management of Patients with Sepsis and Hypotension, A Multicenter Observational Study

To describe and compare early with late vasopressor commencement in emergency department (ED) patients with sepsis and hypotension. This is a sub-study of the ARISE FLUIDS observational study conducted in 70 EDs in Australia and New Zealand. Adults with suspected sepsis and hypotension who received a vasopressor infusion in the first 24 h after ED presentation were included. 'Early' was defined as vasopressor commenced within 2 h from a) sepsis recognition, or b) triage. 177 patients (mean age 68 years) received vasopressors and had a lactate of 3.0 (IQR 2.0-4.9) mmol/L and APACHE II score of 17.8 (SD 6.3). 110 (62%) received a single agent vasopressor with noradrenaline being the most common (n = 74) and 67 (38%) received multiple vasopressors, most commonly metaraminol then noradrenaline (20.3%, n = 36). One-third (34.7%, n = 62) had vasopressors started via a peripheral line. Vasopressors were started within 2 h of sepsis recognition in 74 patients and within 2 h of triage in 24 patients. Both early groups had a higher lactate (3.5 vs. 2.9mmol/L and 5.0 vs. 2.9mmol/L, both p <0.05) and received lower fluid volumes prior to vasopressor commencement (2.0 vs. 2.85 L and 1.55 vs. 2.4 L, both p <0.001), compared to patients receiving vasopressors later. No differences in duration of vasopressor infusion, need for organ support or in-hospital mortality were found. Early vasopressor commencement was associated with the administration of lower intravenous fluid volumes but not with duration of vasopressor use, organ support or mortality. Large prospective studies addressing this question are required.

The Efficacy of vitamin C, thiamine, and corticosteroid therapy in adult sepsis patients: a systematic review and meta-analysis

Previous studies have suggested favorable outcomes of hydrocortisone, ascorbic acid (vitamin C), and thiamine (HAT) therapy in patients with sepsis. However, similar results have not been duplicated in sequential studies. This meta-analysis aimed to reevaluate the value of HAT treatment in patients with sepsis. Electronic databases were searched up until October 2020 for any studies that compared the effect of HAT versus non-HAT use in patients with sepsis. Data from 15 studies (eight randomized controlled trials [RCTs] and seven cohort studies) involving 67,349 patients were included. The results from the RCTs show no significant benefit of triple therapy on hospital mortality (risk ratio [RR], 0.99; P=0.92; I2=0%); intensive care unit (ICU) mortality (RR, 0.77; P=0.20; I2=58%); ICU length of stay (weighted mean difference [WMD], 0.11; P=0.86; I2 =37%) or hospital length of stay (WMD: 0.57; P=0.49; I2=17%), and renal replacement therapy (RR, 0.64; P=0.44; I2=39%). The delta Sequential Organ Failure Assessment (SOFA) score favored treatment after a sensitivity analysis (WMD, –0.72; P=0.01; I2=32%). However, a significant effect was noted for the duration of vasopressor use (WMD, –25.49; P<0.001; I2=46%). The results from cohort studies have also shown no significant benefit of HAT therapy on hospital mortality, ICU mortality, ICU length of stay, length of hospital stay, the delta SOFA score, the use of renal replacement therapy, or vasopressor duration. HAT therapy significantly reduced the duration of vasopressor use and improved the SOFA score but appeared not to have significant benefits in other outcomes for patients with sepsis. Further RCTs can help understand its benefit exclusively.