Annals of Intensive Care最新文献

Background: Pulmonary intravascular thrombus formation has been widely observed in patients with respiratory failure, for example, in patients with SARS-CoV-2 infection (COVID-19). The aim of this study was to evaluate the efficacy/safety of alteplase thrombolysis in COVID-19 severe hypoxemic respiratory failure. In this multicenter, open-label study, patients were randomized to receive alteplase (low- or high-dose) over 5 days plus standard of care (SOC), or SOC alone. The primary endpoint was time to clinical improvement (≥ 2-point decrease on WHO Clinical Progression Scale, or hospital discharge) up to Day 28. Secondary endpoints included all-cause mortality at Day 28, treatment failure at Day 28 and change in arterial oxygen partial pressure/fractional inspired oxygen (PaO₂/FiO₂) ratio at Day 6 versus baseline.

Results: Sixty-nine patients were randomized to alteplase (low- or high-dose) and 35 to SOC; 65% were on high-flow oxygen or non-invasive ventilation at baseline. Median time to clinical improvement was 25 days in the alteplase group and > 28 days (median not reached) in the SOC group. All-cause mortality was 8/69 (12%) versus 10/35 (29%) in the alteplase versus SOC groups, respectively (unadjusted risk difference [RD], - 17% [95% confidence interval (CI) - 34 to 0], p = 0.047; adjusted RD, - 16% [95% CI - 31 to 1], p = 0.058). The PaO₂/FiO₂ ratio (mean [standard deviation]) increased by + 30 (84) mmHg in the alteplase group and decreased by - 12 (59) mmHg in the SOC group (adjusted mean difference vs. SOC, p = 0.052). Differences were greater in patients receiving high-dose alteplase, and in those not receiving invasive ventilation. Eighteen patients (26.1%) in the alteplase group discontinued treatment due to adverse events. Major bleeding was more frequent with alteplase than with SOC (9 vs. 0 patients); no bleeding was fatal. The study closed early due to insufficient patient recruitment.

Conclusion: Alteplase was not associated with faster clinical recovery from COVID-19 severe hypoxemic respiratory failure. A numerical difference in survival and PaO₂/FiO₂ ratio was observed, particularly in patients not receiving invasive ventilation. These exploratory findings merit further investigation in larger patient cohorts that are adequately powered to confirm the hypotheses generated in this study regarding the impact of alteplase on treatment outcomes. Trial registration ClinicalTrials.gov: NCT04640194 (November 23, 2020); https://clinicaltrials.gov/study/NCT04640194 (early discontinuation due to insufficient patient recruitment).

Background: The impairment of endothelial function represents a key pathophysiological mechanism in the development of sepsis. This research aimed to evaluate the prognostic significance of angiopoietin-2 (Ang-2), an endothelial biomarker, in predicting mortality in sepsis patients.

Methods: Chinese and English studies were systematically retrieved in PubMed, Cochrane Library, Embase, WanFang, CNKI, CQVIP, and CBM databases up to July 16, 2023. We conducted a study selection established upon predefined inclusion and exclusion criteria and used the Newcastle-Ottawa scale (NOS) to assess its quality. We extracted available data from the included studies for data analysis.

Results: The final inclusion comprised 33 studies with 4703 participants. According to the NOS, one study was of medium quality, while the rest were of high quality. In comparison to survivors, the levels of Ang-2 in non-survivors were markedly elevated [standardized mean difference (SMD) = 1.08, 95% confidence intervals (CI) 0.68-1.49, P < 0.001], and the same results were also observed in the subgroup that met sepsis 3.0 diagnosis criteria (SMD = 0.63, 95% CI 0.11-1.14, P = 0.017). The results comparing Ang-2 levels between non-survivors and survivors were independent of duration of follow-up, sample sources, type of study, and region. Ang-2 was a risk factor for mortality [odds ratios (OR) = 1.16, 95% CI 1.09-1.23, P < 0.001]. Ang-2 was demonstrated to be able to predict mortality in septic adult patients [area under the curve (AUC) = 0.76, 95% CI 0.70-0.82, P < 0.001].

Conclusions: Ang-2 level was positively correlated with risk of death in sepsis patients. Ang-2 might be a useful and valuable biomarker for predicting mortality in septic adult patients.

Background: It is uncertain whether fluid administration can improve patients with systemic venous congestion and haemodynamic instability. This study aimed to describe the changes in systemic venous congestion and peripheral perfusion parameters induced by a fluid challenge in these patients, and to analyse the influence of the fluid responsiveness status on these changes.

Methods: The study is a single-centre prospective cohort study of 36 critically ill ICU patients with haemodynamic instability and a maximum vena cava diameter ≥ 20 mm. Changes in cardiac index during a fluid challenge (4 mL/kg of lactated Ringer's solution during 5 min) assessed by pulse contour analysis, central venous pressure, ultrasound systemic congestion parameters (portal venous flow pulsatility index, supra hepatic and intrarenal venous Doppler), and peripheral perfusion parameters (capillary refill time and peripheral perfusion index) were assessed in the overall population. All these data were compared between patients presenting a cardiac index increase > 10% during the fluid challenge (fluid responders) and the others (fluid non-responders).

Results: Twenty-eight (78%) patients were admitted for postoperative care following cardiac surgery; their mean ± SD left ventricular ejection fraction was 42 ± 9% and right ventricular dysfunction was found in at least 61% of the patients. The mean ± SD SOFA score was 9 ± 3. Thirteen (36%) patients were fluid responders. The fluid challenge administration induced a significant increase in portal pulsatility index, VExUS score, and central venous pressure without significant difference of these changes between fluid responders and non-responders. No significant change in perfusion parameters was observed.

Conclusion: Fluid administration in patients with haemodynamic instability and systemic venous congestion worsens venous congestion regardless of the fluid responsiveness status, without improving perfusion parameters.

Background: Ciprofol was approved for use in intensive care unit (ICU) patients requiring sedation during mechanical ventilation in July 2022. A pooled post-hoc analysis of phase 2 and phase 3 trials was conducted primarily to explore hypotension-free outcome in ICU patients who required mechanical ventilation and achieved the target light sedation goal at an early stage after being sedated with ciprofol or propofol.

Methods: All eligible ICU patients who were expected to require sedation for 6-24 h were randomly assigned in a 2:1 ratio to either a ciprofol or propofol group. Ciprofol or propofol was initially infused at loading doses of 0.5 or 1.0 mg/kg followed by maintenance doses of 0.3 or 1.5 mg/kg/h. Ciprofol or propofol dosages were adjusted up or down at rates of 0.05-0.10 mg/kg/h or 0.25-0.50 mg/kg/h, respectively, to achieve the target light sedation (a Richmond Agitation-Sedation Scale of -2 to + 1). The primary post-hoc outcome was the hypotension-free rate in patients who had achieved the target sedation goal after 30-min administration of ciprofol or propofol.

Results: In total, 174 patients were enrolled for pooled post-hoc analysis, of whom 116 and 58 were assigned to the ciprofol and propofol groups, respectively. The hypotension-free rate was significantly higher in patients who achieved the target sedation goal after 30-min administration of ciprofol (93.0% vs. 81.0%, P = 0.018), and especially in the subgroups of males and patients aged < 65 years. Multivariable analysis revealed that ciprofol treatment, a younger age and lower baseline body mass index were independent favorable predictors for a higher hypotension-free rate in patients who achieved the target sedation goal after 30-min of drug administration. Moreover, hypotension-free patients who reached the target sedation level after 30 min had a more favorable short-term prognosis including a lower incidence of drug-related treatment-emergent adverse events, shorter time to extubation and fewer dose adjustments of ciprofol or propofol (all P < 0.05).

Conclusion: ICU patients undergoing mechanical ventilation and sedated with ciprofol had significantly lower rate of hypotension during the early phase of achieving light sedation during a 6-24 h period, leading to a more favorable short-term prognosis (within 24 h).

Trial registration: Phase 2 trial (clinicaltrials.gov, NCT04147416. Registered November 1, 2019, https://classic.

Clinicaltrials: gov/ct2/show/NCT04147416 ) and phase 3 trial (clinicaltrials.gov, NCT04620031. Registered November 6, 2020, https://classic.

Clinicaltrials: gov/ct2/show/NCT04620031 ).

Background: Reduced muscle mass upon admission and development of muscle wasting are frequent in critically ill patients, and linked to unfavorable outcomes. Muscle ultrasound is a promising instrument for evaluating muscle mass. We summarized the findings of lower limb muscle ultrasound values and investigated how the muscle ultrasound parameters of the examination or the patient characteristics influence the results.

Methods: Systematic review and meta-analysis of studies of lower limb ultrasound critically ill adults. PubMed, CINAHL, Embase, PEDro and Web of Science were searched. PRISMA guidelines were followed, and studies evaluated with the appropriate NIH quality assessment tool. A meta-analysis was conducted to compare the values at admission, short and long follow-up during ICU stay, and the association between baseline values and patient characteristics or ultrasound parameters was investigated with a meta-regression.

Results: Sixty-six studies (3839 patients) were included. The main muscles investigated were rectus femoris cross-sectional area (RF-CSA, n = 33/66), quadriceps muscle layer thickness (n = 32/66), and rectus femoris thickness (n = 19/66). Significant differences were found in the anatomical landmark and ultrasound settings. At ICU admission, RF-CSA ranged from 1.1 [0.73-1.47] to 6.36 [5.45-7.27] cm² (pooled average 2.83 [2.29-3.37] cm²) with high heterogeneity among studies (I² = 98.43%). Higher age, higher BMI, more distal landmark and the use of probe compression were associated with lower baseline muscle mass.

Conclusions: Measurements of muscle mass using ultrasound varied with reference to patient characteristics, patient position, anatomical landmarks used for measurement, and the level of compression applied by the probe; this constrains the external validity of the results and highlights the need for standardization.

Study registration: PROSPERO CRD42023420376.

Background: Electrical Impedance Tomography (EIT) can quantify ventilation in the two lungs and be used to measure the airway opening pressure (AOP) of each lung. Asymmetrical AOPs can cause inter-lung insufflation delay.

Objectives: To assess the relation between AOP asymmetry and inter-lung insufflation delay at different PEEP levels.

Methods: Patients with acute hypoxemic respiratory failure and airway closure were included. Low-flow pressure-volume curves and EIT signal were recorded during controlled ventilation and for some patients in pressure support ventilation.

Results: 23 patients were studied, 22 patients had ARDS, 9 patients had asymmetrical airway closure with an AOP of 10 [6-13] cmH₂0 in the sicker lung (AOP_sicker) vs. 5 [3-9, ] cmH₂0 in the healthier lung. During a low flow inflation, the inter-lung inflation delay was 0 [0-112]ms vs. 1450 [375-2400]ms in patients without or with asymmetrical AOPs, p < 0.0001. This delay was correlated to the difference of AOP between the 2 lungs, Spearman R² = 0.800, p < 0.0001. During tidal ventilation, median delay was 0 [0-62] ms vs. 150 [50-355] ms in patients without vs. with asymmetry, p = 0.019. Setting PEEP at the crossing point of a decremental EIT-based PEEP trial decreased the inter-lung insufflation delay. During pressure support insufflation delay could still be measured and was reduced by increasing PEEP from 5 to 10 cmH₂O in patient with asymmetrical lung injury.

Conclusion: In asymmetrical airway closure, titrating PEEP can minimize inter-lung insufflation delay and can be monitored by EIT. Reducing the delay and reducing ventilation asymmetry is also feasible during pressure support ventilation when low flow inflation curves cannot be performed.