Association of early mobility with the incidence of deep-vein thrombosis and mortality among critically ill patients: a post hoc analysis of PREVENT trial.

BACKGROUND: This study assessed the mobility levels among critically ill patients and the association of early mobility with incident proximal lower-limb deep-vein thrombosis and 90-day mortality. METHODS: This was a post hoc analysis of the multicenter PREVENT trial, which evaluated adjunctive intermittent pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis with an expected ICU stay ≥ 72 h and found no effect on the primary outcome of incident proximal lower-limb deep-vein thrombosis. Mobility levels were documented daily up to day 28 in the ICU using a tool with an 8-point ordinal scale. We categorized patients according to mobility levels within the first 3 ICU days into three groups: early mobility level 4-7 (at least active standing), 1-3 (passive transfer from bed to chair or active sitting), and 0 (passive range of motion). We evaluated the association of early mobility and incident lower-limb deep-vein thrombosis and 90-day mortality by Cox proportional models adjusting for randomization and other co-variables. RESULTS: Of 1708 patients, only 85 (5.0%) had early mobility level 4-7 and 356 (20.8%) level 1-3, while 1267 (74.2%) had early mobility level 0. Patients with early mobility levels 4-7 and 1-3 had less illness severity, femoral central venous catheters, and organ support compared to patients with mobility level 0. Incident proximal lower-limb deep-vein thrombosis occurred in 1/85 (1.3%) patients in the early mobility 4-7 group, 7/348 (2.0%) patients in mobility 1-3 group, and 50/1230 (4.1%) patients in mobility 0 group. Compared with early mobility group 0, mobility groups 4-7 and 1-3 were not associated with differences in incident proximal lower-limb deep-vein thrombosis (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI] 0.16, 8.90; p = 0.87 and 0.91, 95% CI 0.39, 2.12; p = 0.83, respectively). However, early mobility groups 4-7 and 1-3 had lower 90-day mortality (aHR 0.47, 95% CI 0.22, 1.01; p = 0.052, and 0.43, 95% CI 0.30, 0.62; p < 0.0001, respectively). CONCLUSIONS: Only a small proportion of critically ill patients with an expected ICU stay ≥ 72 h were mobilized early. Early mobility was associated with reduced mortality, but not with different incidence of deep-vein thrombosis. This association does not establish causality, and randomized controlled trials are required to assess whether and to what extent this association is modifiable. TRIAL REGISTRATION: The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103 (registered on 3 November 2013) and Current controlled trials, ID: ISRCTN44653506 (registered on 30 October 2013).

Impact of a national collaborative project to improve the care of mechanically ventilated patients.

This prospective quasi-experimental study from the NASAM (National Approach to Standardize and Improve Mechanical Ventilation) collaborative assessed the impact of evidence-based practices including subglottic suctioning, daily assessment for spontaneous awakening trial (SAT), spontaneous breathing trial (SBT), head of bed elevation, and avoidance of neuromuscular blockers unless otherwise indicated. The study outcomes included VAE (primary) and intensive care unit (ICU) mortality. Changes in daily care process measures and outcomes were evaluated using repeated measures mixed modeling. The results were reported as incident rate ratio (IRR) for each additional month with 95% confidence interval (CI). A comprehensive program that included education on evidence-based practices for optimal care of mechanically ventilated patients with real-time benchmarking of daily care process measures to drive improvement in forty-two ICUs from 26 hospitals in Saudi Arabia (>27,000 days of observation). Compliance with subglottic suctioning, SAT and SBT increased monthly during the project by 3.5%, 2.1% and 1.9%, respectively (IRR 1.035, 95%CI 1.007-1.064, p = 0.0148; 1.021, 95% CI 1.010-1.032, p = 0.0003; and 1.019, 95%CI 1.009-1.029, p = 0.0001, respectively). The use of neuromuscular blockers decreased monthly by 2.5% (IRR 0.975, 95%CI 0.953-0.998, p = 0.0341). The compliance with head of bed elevation was high at baseline and did not change over time. Based on data for 83153 ventilator days, VAE rate was 15.2/1000 ventilator day (95%CI 12.6-18.1) at baseline and did not change during the project (IRR 1.019, 95%CI 0.985-1.053, p = 0.2812). Based on data for 8523 patients; the mortality was 30.4% (95%CI 27.4-33.6) at baseline, and decreased monthly during the project by 1.6% (IRR 0.984, 95%CI 0.973-0.996, p = 0.0067). A national quality improvement collaborative was associated with improvements in daily care processes. These changes were associated with a reduction in mortality but not VAEs. Registration The study is registered in clinicaltrials.gov (NCT03790150).

The effect of intermittent pneumatic compression on deep-vein thrombosis and ventilation-free days in critically ill patients with heart failure.

There are contradictory data regarding the effect of intermittent pneumatic compression (IPC) on the incidence of deep-vein thrombosis (DVT) and heart failure (HF) decompensation in critically ill patients. This study evaluated the effect of adjunctive use of IPC on the rate of incident DVT and ventilation-free days among critically ill patients with HF. In this pre-specified secondary analysis of the PREVENT trial (N = 2003), we compared the effect of adjunctive IPC added to pharmacologic thromboprophylaxis (IPC group), with pharmacologic thromboprophylaxis alone (control group) in critically ill patients with HF. The presence of HF was determined by the treating teams according to local practices. Patients were stratified according to preserved (≥ 40%) versus reduced (< 40%) left ventricular ejection fraction, and by the New York Heart Association (NYHA) classification. The primary outcome was incident proximal lower-limb DVT, determined with twice weekly venous Doppler ultrasonography. As a co-primary outcome, we evaluated ventilation-free days as a surrogate for clinically important HF decompensation. Among 275 patients with HF, 18 (6.5%) patients had prevalent proximal lower-limb DVT (detected on trial day 1 to 3). Of 257 patients with no prevalent DVT, 11/125 (8.8%) patients in the IPC group developed incident proximal lower-limb DVT compared to 6/132 (4.5%) patients in the control group (relative risk, 1.94; 95% confidence interval, 0.74-5.08, p = 0.17). There was no significant difference in ventilator-free days between the IPC and control groups (median 21 days versus 25 days respectively, p = 0.17). The incidence of DVT with IPC versus control was not different across NYHA classes (p value for interaction = 0.18), nor across patients with reduced and preserved ejection fraction (p value for interaction = 0.15). Ventilator-free days with IPC versus control were also not different across NYHA classes nor across patients with reduced or preserved ejection fraction. In conclsuion, the use of adjunctive IPC compared with control was associated with similar rate of incident proximal lower-limb DVT and ventilator-free days in critically ill patients with HF.Trial registration: The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103 (registered on 3 November 2013, https://clinicaltrials.gov/ct2/show/study/NCT02040103 ) and Current controlled trials, ID: ISRCTN44653506 (registered on 30 October 2013).

Association between phosphate disturbances and mortality among critically ill patients with sepsis or septic shock.

OBJECTIVE: The aim of this study is to examine the association of hypophosphatemia and hyperphosphatemia on the first day of ICU admission with mortality in septic critically ill patients. METHODS: In this retrospective cohort study, all adult patients who were admitted to the medical-surgical ICUs between 2014 and 2017 with sepsis or septic shock were categorized as having hypophosphatemia, normophosphatemia and hyperphosphatemia based on day 1 serum phosphate values. We compared the clinical characteristics and outcomes between the three groups. We used multivariate analysis to examine the association of hypophosphatemia and hyperphosphatemia with these outcomes. RESULTS: Of the 1422 patients enrolled in the study, 188 (13%) had hypophosphatemia, 865 (61%) normophosphatemia and 369 (26%) had hyperphosphatemia. The patients in the hyperphosphatemia group had significantly lower GCS, higher APACHE II scores, higher serum creatinine, increased use of vasopressors, and required more mechanical ventilation with lower PaO2/FiO2 ratio compared with the other two groups. In addition, the hyperphosphatemia group showed significantly higher ICU and hospital mortality in comparison with the other two groups. CONCLUSION: Hyperphosphatemia and not hypophosphatemia on the first ICU admission day was associated with an increase in the ICU and hospital mortality in septic critically ill patients.

Surveillance or no surveillance ultrasonography for deep vein thrombosis and outcomes of critically ill patients: a pre-planned sub-study of the PREVENT trial.

PURPOSE: We examined the association between surveillance for deep vein thrombosis (DVT) among medical-surgical critically ill patients by twice-weekly ultrasonography and 90-day all-cause mortality. METHODS: This was a pre-planned sub-study of the Pneumatic Compression for Preventing Venous Thromboembolism (PREVENT) trial (Clinicaltrials.gov: NCT02040103) that compared addition of intermittent pneumatic compression (IPC) to pharmacologic prophylaxis versus pharmacologic prophylaxis alone. The surveillance group included enrolled patients in the trial, while the non-surveillance group included eligible non-enrolled patients. Using logistic regression and Cox proportional hazards models, we examined the association of surveillance with the primary outcome of 90-day mortality. Secondary outcomes were DVT and pulmonary embolism (PE). RESULTS: The surveillance group consisted of 1682 patients and the non-surveillance group included 383 patients. Using Cox proportional hazards model with bootstrapping, surveillance was associated with a decrease in 90-day mortality (adjusted HR 0.75; 95% CI 0.57, 0.98). Surveillance was associated with earlier diagnosis of DVT [(median 4 days (IQR 2, 10) vs. 20 days (IQR 16, 22)] and PE [median 4 days (IQR 2.5, 5) vs. 7.5 days (IQR 6.1, 28.9)]. There was an increase in diagnosis of DVT (adjusted HR 5.49; 95% CI 2.92, 13.02) with no change in frequency in diagnosis of PE (adjusted HR 0.56; 95% CI 0.19, 1.91). CONCLUSIONS: Twice-weekly surveillance ultrasonography was associated with an increase in DVT detection, reduction in diagnostic testing for non-lower limb DVT and PE, earlier diagnosis of DVT and PE, and lower 90-day mortality. TRIAL REGISTRATION: The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103. Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506. Registered on 30 October 2013.

National Approach to Standardize and Improve Mechanical Ventilation.

NASAM (National Approach to Standardize and Improve Mechanical Ventilation) is a national collaborative quality improvement project in Saudi Arabia. It aims to improve the care of mechanically ventilated patients by implementing evidence-based practices with the goal of reducing the rate of ventilator-associated events and therefore reducing mortality, mechanical ventilation duration and intensive care unit (ICU) length of stay. The project plans to extend the implementation to a total of 100 ICUs in collaboration with multiple health systems across the country. As of March 22, 2019, a total of 78 ICUs have registered from 6 different health sectors, 48 hospitals, and 27 cities. The leadership support in all health sectors for NASAM speaks of the commitment to improve the care of mechanically ventilated patients across the kingdom.

Surveillance or no surveillance for deep venous thrombosis and outcomes of critically ill patients: A study protocol and statistical analysis plan.

OBJECTIVE: Surveillance ultrasounds in critically ill patients detect many deep venous thrombi (DVTs) that would otherwise go unnoticed. However, the impact of surveillance for DVT on mortality among critically ill patients remains unclear. DESIGN: We are conducting a multicenter, multinational randomized controlled trial that examines the effectiveness of adjunct intermittent pneumatic compression use with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on the incidence of proximal lower extremity DVT in critically ill patients (the PREVENT trial). Enrolled patients undergo twice weekly surveillance ultrasounds of the lower extremities as part of the study procedures. We plan to compare enrolled patients who have surveillance ultrasounds to patients who meet the eligibility criteria but are not enrolled (eligible non-enrolled patients) and only who will have ultrasounds performed at the clinical team's discretion. We hypothesize that twice-weekly ultrasound surveillance for DVT in critically ill patients who are receiving thromboprophylaxis will have more DVTs detected, and consequently, fewer pulmonary emboli and lower all-cause 90-day mortality. DISCUSSION: We developed a detailed a priori plan to guide the analysis of the proposed study and enhance the validity of its results.

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial.

BACKGROUND: The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. METHODS/DESIGN: In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is "incident" proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. DISCUSSION: Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT02040103 . Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506 . Registered on 30 October 2013.

Thromboprophylaxis using combined intermittent pneumatic compression and pharmacologic prophylaxis versus pharmacologic prophylaxis alone in critically ill patients: study protocol for a randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) remains a common problem in critically ill patients. Pharmacologic prophylaxis is currently the standard of care based on high-level evidence from randomized controlled trials. However, limited evidence exists regarding the effectiveness of intermittent pneumatic compression (IPC) devices. The Pneumatic compREssion for preventing VENous Thromboembolism (PREVENT trial) aims to determine whether the adjunct use of IPC with pharmacologic prophylaxis compared to pharmacologic prophylaxis alone in critically ill patients reduces the risk of VTE. METHODS/DESIGN: The PREVENT trial is a multicenter randomized controlled trial, which will recruit 2000 critically ill patients from over 20 hospitals in three countries. The primary outcome is the incidence of proximal lower extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the scans are blinded to intervention allocation, whereas the patients and caregivers are unblinded. The trial has 80 % power to detect a 3 % absolute risk reduction in proximal DVT from 7 to 4 %. DISCUSSION: The first patient was enrolled in July 2014. As of May 2015, a total of 650 patients have been enrolled from 13 centers in Saudi Arabia, Canada and Australia. The first interim analysis is anticipated in July 2016. We expect to complete recruitment by 2018. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02040103 (registered on 3 November 2013). Current controlled trials: ISRCTN44653506 (registered on 30 October 2013).