The efficacy and safety of prokinetic agents in critically ill patients receiving enteral nutrition: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Intolerance to enteral nutrition is common in critically ill adults, and may result in significant morbidity including ileus, abdominal distension, vomiting and potential aspiration events. Prokinetic agents are prescribed to improve gastric emptying. However, the efficacy and safety of these agents in critically ill patients is not well-defined. Therefore, we conducted a systematic review and meta-analysis to determine the efficacy and safety of prokinetic agents in critically ill patients. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library from inception up to January 2016. Eligible studies included randomized controlled trials (RCTs) of critically ill adults assigned to receive a prokinetic agent or placebo, and that reported relevant clinical outcomes. Two independent reviewers screened potentially eligible articles, selected eligible studies, and abstracted pertinent data. We calculated pooled relative risk (RR) for dichotomous outcomes and mean difference for continuous outcomes, with the corresponding 95 % confidence interval (CI). We assessed risk of bias using Cochrane risk of bias tool, and the quality of evidence using grading of recommendations assessment, development, and evaluation (GRADE) methodology. RESULTS: Thirteen RCTs (enrolling 1341 patients) met our inclusion criteria. Prokinetic agents significantly reduced feeding intolerance (RR 0.73, 95 % CI 0.55, 0.97; P = 0.03; moderate certainty), which translated to 17.3 % (95 % CI 5, 26.8 %) absolute reduction in feeding intolerance. Prokinetics also reduced the risk of developing high gastric residual volumes (RR 0.69; 95 % CI 0.52, 0.91; P = 0.009; moderate quality) and increased the success of post-pyloric feeding tube placement (RR 1.60, 95 % CI 1.17, 2.21; P = 0.004; moderate quality). There was no significant improvement in the risk of vomiting, diarrhea, intensive care unit (ICU) length of stay or mortality. Prokinetic agents also did not significantly increase the rate of diarrhea. CONCLUSION: There is moderate-quality evidence that prokinetic agents reduce feeding intolerance in critically ill patients compared to placebo or no intervention. However, the impact on other clinical outcomes such as pneumonia, mortality, and ICU length of stay is unclear

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients ( CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640

Imaging features and safety and efficacy of endovascular stroke treatment: a meta-analysis of individual patient-level data

Background: Evidence regarding whether imaging can be used effectively to select patients for endovascular thrombectomy (EVT) is scarce. We aimed to investigate the association between baseline imaging features and safety and efficacy of EVT in acute ischaemic stroke caused by anterior large-vessel occlusion. Methods: In this meta-analysis of individual patient-level data, the HERMES collaboration identified in PubMed seven randomised trials in endovascular stroke that compared EVT with standard medical therapy, published between Jan 1, 2010, and Oct 31, 2017. Only trials that required vessel imaging to identify patients with proximal anterior circulation ischaemic stroke and that used predominantly stent retrievers or second-generation neurothrombectomy devices in the EVT group were included. Risk of bias was assessed with the Cochrane handbook methodology. Central investigators, masked to clinical information other than stroke side, categorised baseline imaging features of ischaemic change with the Alberta Stroke Program Early CT Score (ASPECTS) or according to involvement of more than 33% of middle cerebral artery territory, and by thrombus volume, hyperdensity, and collateral status. The primary endpoint was neurological functional disability scored on the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included symptomatic intracranial haemorrhage, parenchymal haematoma type 2 within 5 days of randomisation, and mortality within 90 days. For the primary analysis, we used mixed-methods ordinal logistic regression adjusted for age, sex, National Institutes of Health Stroke Scale score at admission, intravenous alteplase, and time from onset to randomisation, and we used interaction terms to test whether imaging categorisation at baseline modifies the association between treatment and outcome. This meta-analysis was prospectively designed by the HERMES executive committee but has not been registered. Findings: Among 1764 pooled patients, 871 were allocated to the EVT group and 893 to the control group. Risk of bias was low except in the THRACE study, which used unblinded assessment of outcomes 90 days after randomisation and MRI predominantly as the primary baseline imaging tool. The overall treatment effect favoured EVT (adjusted common odds ratio [cOR] for a shift towards better outcome on the mRS 2·00, 95% CI 1·69–2·38; p<0·0001). EVT achieved better outcomes at 90 days than standard medical therapy alone across a broad range of baseline imaging categories. Mortality at 90 days (14·7% vs 17·3%, p=0·15), symptomatic intracranial haemorrhage (3·8% vs 3·5%, p=0·90), and parenchymal haematoma type 2 (5·6% vs 4·8%, p=0·52) did not differ between the EVT and control groups. No treatment effect modification by baseline imaging features was noted for mortality at 90 days and parenchymal haematoma type 2. Among patients with ASPECTS 0–4, symptomatic intracranial haemorrhage was seen in ten (19%) of 52 patients in the EVT group versus three (5%) of 66 patients in the control group (adjusted cOR 3·94, 95% CI 0·94–16·49; pinteraction=0·025), and among patients with more than 33% involvement of middle cerebral artery territory, symptomatic intracranial haemorrhage was observed in 15 (14%) of 108 patients in the EVT group versus four (4%) of 113 patients in the control group (4·17, 1·30–13·44, pinteraction=0·012). Interpretation: EVT achieves better outcomes at 90 days than standard medical therapy across a broad range of baseline imaging categories, including infarcts affecting more than 33% of middle cerebral artery territory or ASPECTS less than 6, although in these patients the risk of symptomatic intracranial haemorrhage was higher in the EVT group than the control group. This analysis provides preliminary evidence for potential use of EVT in patients with large infarcts at baseline. Funding: Medtronic

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

Late Window Imaging Selection for Endovascular Therapy of Large Vessel Occlusion Stroke: An International Survey

Background Current stroke guidelines recommend advanced imaging (computed tomography [CT] perfusion or magnetic resonance imaging) prior to endovascular therapy (EVT) in patients with late presentation of large vessel occlusion. Adherence to guidelines may be constrained by resources or timely access to imaging. We sought to understand the factors which influence late window imaging selection for EVT candidates with large vessel occlusion. Methods We conducted an international survey from January to May 2022. The questions aimed to identify advanced imaging and treatment decisions based on access to imaging, time delays, and simulated patient scenarios. Results There were 3000 invited participants and 1506 respondents, the majority (89.6%) from comprehensive stroke centers in high‐income countries. Neurointerventionalists comprised 31.8% and noninterventionalists 68.2% of respondents. Overall, 70.7% reported routine use of advanced imaging for late EVT selection, and 63.6% reported its usage in every case. There was greater availability of advanced imaging in comprehensive stroke centers versus primary stroke centers (67.0% versus 33.7%; P<0.0001), and high‐ versus low‐middle income countries (70.5% versus 44.5%; P<0.0001). When presented with a late window patient, 41.6% would complete CT perfusion or magnetic resonance imaging prior to EVT, 25.4% would perform CT perfusion or magnetic resonance imaging prior to IVT and EVT, and 25.8% would refer to EVT without advanced imaging. If advanced imaging was not readily available, 70.1% would refer a patient to EVT based on CT in the late window. Additional time delay within 20 minutes to obtain advanced imaging was considered acceptable in 77.7% of respondents. Conclusion Current guidelines for imaging late window EVT candidates are inconsistent with imaging decisions by physicians. Most respondents consider an imaging delay of greater than 20 minutes unacceptable. Access to advanced imaging was greater in comprehensive stroke centers and high‐income countries. In the case of limited access most respondents would consider EVT based on CT only