Background Difficult weaning frequently develops in ventilated patients and is associated with poor outcome. In neurally adjusted ventilatory assist, the ventilator is controlled by diaphragm electrical activity, which has been shown to improve patient–ventilator interaction. The objective of this study was to compare neurally adjusted ventilatory assist and pressure support ventilation in patients difficult to wean from mechanical ventilation. Methods In this nonblinded randomized clinical trial, difficult-to-wean patients (n = 99) were randomly assigned to neurally adjusted ventilatory assist or pressure support ventilation mode. The primary outcome was the duration of weaning. Secondary outcomes included the proportion of successful weaning, patient–ventilator asynchrony, ventilator-free days, and mortality. Weaning duration was calculated as 28 days for patients under mechanical ventilation at day 28 or deceased before day 28 without successful weaning. Results Weaning duration in all patients was statistically significant shorter in the neurally adjusted ventilatory assist group (n = 47) compared with the pressure support ventilation group (n = 52; 3.0 [1.2 to 8.0] days vs. 7.4 [2.0 to 28.0], mean difference: −5.5 [95% CI, −9.2 to −1.4], P = 0.039). Post hoc sensitivity analysis also showed that the neurally adjusted ventilatory assist group had shorter weaning duration (hazard ratio, 0.58; 95% CI, 0.34 to 0.98). The proportion of patients with successful weaning from invasive mechanical ventilation was higher in neurally adjusted ventilatory assist (33 of 47 patients, 70%) compared with pressure support ventilation (25 of 52 patients, 48%; respiratory rate for neurally adjusted ventilatory assist: 1.46 [95% CI, 1.04 to 2.05], P = 0.026). The number of ventilator-free days at days 14 and 28 was statistically significantly higher in neurally adjusted ventilatory assist compared with pressure support ventilation. Neurally adjusted ventilatory assist improved patient ventilator interaction. Mortality and length of stay in the intensive care unit and in the hospital were similar among groups. Conclusions In patients difficult to wean, neurally adjusted ventilatory assist decreased the duration of weaning and increased ventilator-free days. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

IntroductionIntrinsic positive end-expiratory pressure (PEEPi) is a “threshold” load that must be overcome to trigger conventional pneumatically-controlled pressure support (PSP) in chronic obstructive pulmonary disease (COPD). Application of extrinsic PEEP (PEEPe) reduces trigger delays and mechanical inspiratory efforts. Using the diaphragm electrical activity (EAdi), neurally controlled pressure support (PSN) could hypothetically eliminate asynchrony and reduce mechanical inspiratory effort, hence substituting the need for PEEPe. The primary objective of this study was to show that PSN can reduce the need for PEEPe to improve patient-ventilator interaction and to reduce both the “pre-trigger” and “total inspiratory” neural and mechanical efforts in COPD patients with PEEPi. A secondary objective was to evaluate the impact of applying PSN on breathing pattern.MethodsTwelve intubated and mechanically ventilated COPD patients with PEEPi ≥ 5 cm H2O underwent comparisons of PSP and PSN at different levels of PEEPe (at 0 %, 40 %, 80 %, and 120 % of static PEEPi, for 12 minutes at each level on average), at matching peak airway pressure. We measured flow, airway pressure, esophageal pressure, and EAdi, and analyzed neural and mechanical efforts for triggering and total inspiration. Patient-ventilator interaction was analyzed with the NeuroSync index.ResultsMean airway pressure and PEEPe were comparable for PSP and PSN at same target levels. During PSP, the NeuroSync index was 29 % at zero PEEPe and improved to 21 % at optimal PEEPe (P < 0.05). During PSN, the NeuroSync index was lower (<7 %, P < 0.05) regardless of PEEPe. Both pre-trigger (P < 0.05) and total inspiratory mechanical efforts (P < 0.05) were consistently higher during PSP compared to PSN at same PEEPe. The change in total mechanical efforts between PSP at PEEPe0% and PSN at PEEPe0% was not different from the change between PSP at PEEPe0% and PSP at PEEPe80%.ConclusionPSN abolishes the need for PEEPe in COPD patients, improves patient-ventilator interaction, and reduces the inspiratory mechanical effort to breathe.Trial registrationClinicaltrials.gov NCT02114567. Registered 04 November 2013.

Background: The associations of frailty with the risk of mortality and resource utilization in the elderly patients admitted to intensive care unit (ICU) remain unclear. To address these issues, we performed a meta-analysis to determine whether frailty is associated with adverse outcomes and increased resource utilization in elderly patients admitted to the ICU.Methods: We searched PubMed, EMBASE, ScienceDirect, and Cochrane Central Register of Controlled Trials through August 2021 to identify the relevant studies that investigated frailty in elderly (≥ 65 years old) patients admitted to an ICU and compared outcomes and resource utilization between frail and non-frail patients. The primary outcome was mortality. We also investigated the prevalence of frailty and the impact of frailty on the health resource utilization, such as hospital length of stay (LOS) and resource utilization of ICU.Results: A total of 13 observational studies enrolling 64,279 participants (28,951 frail and 35,328 non-frail) were finally included. Frailty was associated with an increased risk of short-term mortality (10 studies, relative risk [RR]: 1.70; 95% CI: 1.45–1.98), in-hospital mortality (five studies, RR: 1.73; 95% CI: 1.55–1.93), and long-term mortality (six studies, RR: 1.86; 95% CI: 1.44–2.42). Subgroup analysis showed that retrospective studies identified a stronger correlation between frailty and hospital LOS (three studies, MD 1.14 d; 95% CI: 0.92–1.36).Conclusions: Frailty is common in the elderly patients admitted to ICU, and is associated with increased mortality and prolonged hospital LOS.Trial registration: This study was registered in the PROSPERO database (CRD42020207242).

Background: Catecholamines are the first-line vasopressors used in patients with septic shock. However, the search for novel drug candidates is still of great importance due to the development of adrenergic hyposensitivity accompanied by a decrease in catecholamine activity. Terlipressin (TP) is a synthetic vasopressin analogue used in the management of patients with septic shock. In the current study, we aimed to compare the effects of TP and catecholamine infusion in treating septic shock patients. Methods: A systematic review and meta-analysis was conducted by searching articles published in PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials between inception and July 2018. We only selected randomized controlled trials evaluating the use of TP and catecholamine in adult patients with septic shock. The primary outcome was overall mortality. The secondary outcomes were the ICU length of stay, haemodynamic changes, tissue perfusion, renal function, and adverse events. Results: A total of 9 studies with 850 participants were included in the analysis. Overall, no significant difference in mortality was observed between the TP and catecholamine groups (risk ratio(RR), 0.85 (0.70 to 1.03); P = 0.09). In patients < 60 years old, the mortality rate was lower in the TP group than in the catecholamine group (RR, 0.66 (0.50 to 0.86); P = 0.002). There was no significant difference in the ICU length of stay (mean difference, MD), − 0.28 days; 95% confidence interval (CI), − 1.25 to 0.69; P = 0.58). Additionally, TP improved renal function. The creatinine level was decreased in patients who received TP therapy compared to catecholamine-treated participants (standard mean difference, SMD), − 0.65; 95% CI, − 1.09 to − 0.22; P = 0.003). No significant difference was found regarding the total adverse events (Odds Ratio(OR), 1.48(0.51 to 4.24); P = 0.47), whereas peripheral ischaemia was more common in the TP group (OR, 8.65(1.48 to 50.59); P = 0.02). Conclusion: The use of TP was associated with reduced mortality in septic shock patients less than 60 years old. TP may also improve renal function and cause more peripheral ischaemia. PROSPERO registry: CRD42016035872.