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).

Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis.

BACKGROUND: Whether adjunctive intermittent pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis would result in a lower incidence of deep-vein thrombosis than pharmacologic thromboprophylaxis alone is uncertain. METHODS: We randomly assigned patients who were considered adults according to the local standards at the participating sites (≥14, ≥16, or ≥18 years of age) within 48 hours after admission to an intensive care unit (ICU) to receive either intermittent pneumatic compression for at least 18 hours each day in addition to pharmacologic thromboprophylaxis with unfractionated or low-molecular-weight heparin (pneumatic compression group) or pharmacologic thromboprophylaxis alone (control group). The primary outcome was incident (i.e., new) proximal lower-limb deep-vein thrombosis, as detected on twice-weekly lower-limb ultrasonography after the third calendar day since randomization until ICU discharge, death, attainment of full mobility, or trial day 28, whichever occurred first. RESULTS: A total of 2003 patients underwent randomization - 991 were assigned to the pneumatic compression group and 1012 to the control group. Intermittent pneumatic compression was applied for a median of 22 hours (interquartile range, 21 to 23) daily for a median of 7 days (interquartile range, 4 to 13). The primary outcome occurred in 37 of 957 patients (3.9%) in the pneumatic compression group and in 41 of 985 patients (4.2%) in the control group (relative risk, 0.93; 95% confidence interval [CI], 0.60 to 1.44; P = 0.74). Venous thromboembolism (pulmonary embolism or any lower-limb deep-vein thrombosis) occurred in 103 of 991 patients (10.4%) in the pneumatic compression group and in 95 of 1012 patients (9.4%) in the control group (relative risk, 1.11; 95% CI, 0.85 to 1.44), and death from any cause at 90 days occurred in 258 of 990 patients (26.1%) and 270 of 1011 patients (26.7%), respectively (relative risk, 0.98; 95% CI, 0.84 to 1.13). CONCLUSIONS: Among critically ill patients who were receiving pharmacologic thromboprophylaxis, adjunctive intermittent pneumatic compression did not result in a significantly lower incidence of proximal lower-limb deep-vein thrombosis than pharmacologic thromboprophylaxis alone. (Funded by King Abdulaziz City for Science and Technology and King Abdullah International Medical Research Center; PREVENT ClinicalTrials.gov number, NCT02040103; Current Controlled Trials number, ISRCTN44653506.).

Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection.

BACKGROUND: Since September 2012, 170 confirmed infections with Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization, including 72 deaths. Data on critically ill patients with MERS-CoV infection are limited. OBJECTIVE: To describe the critical illness associated with MERS-CoV. DESIGN: Case series. SETTING: 3 intensive care units (ICUs) at 2 tertiary care hospitals in Saudi Arabia. PATIENTS: 12 patients with confirmed or probable MERS-CoV infection. MEASUREMENTS: Presenting symptoms, comorbid conditions, pulmonary and extrapulmonary manifestations, measures of severity of illness and organ failure, ICU course, and outcome are described, as are the results of surveillance of health care workers (HCWs) and patients with potential exposure. RESULTS: Between December 2012 and August 2013, 114 patients were tested for suspected MERS-CoV; of these, 11 ICU patients (10%) met the definition of confirmed or probable cases. Three of these patients were part of a health care-associated cluster that also included 3 HCWs. One HCW became critically ill and was the 12th patient in this case series. Median Acute Physiology and Chronic Health Evaluation II score was 28 (range, 16 to 36). All 12 patients had underlying comorbid conditions and presented with acute severe hypoxemic respiratory failure. Most patients (92%) had extrapulmonary manifestations, including shock, acute kidney injury, and thrombocytopenia. Five (42%) were alive at day 90. Of the 520 exposed HCWs, only 4 (1%) were positive. LIMITATION: The sample size was small. CONCLUSION: MERS-CoV causes severe acute hypoxemic respiratory failure and considerable extrapulmonary organ dysfunction and is associated with high mortality. Community-acquired and health care-associated MERS-CoV infection occurs in patients with chronic comorbid conditions. The health care-associated cluster suggests that human-to-human transmission does occur with unprotected exposure. PRIMARY FUNDING SOURCE: None.

Performance of Risk Assessment Models for VTE in Patients Who Are Critically Ill Receiving Pharmacologic Thromboprophylaxis: A Post Hoc Analysis of the Pneumatic Compression for Preventing VTE Trial.

BACKGROUND: The diagnostic performance of the available risk assessment models for VTE in patients who are critically ill receiving pharmacologic thromboprophylaxis is unclear. RESEARCH QUESTION: For patients who are critically ill receiving pharmacologic thromboprophylaxis, do risk assessment models predict who would develop VTE or who could benefit from adjunctive pneumatic compression for thromboprophylaxis? STUDY DESIGN AND METHODS: In this post hoc analysis of the Pneumatic Compression for Preventing VTE (PREVENT) trial, different risk assessment models for VTE (ICU-VTE, Kucher, Intermountain, Caprini, Padua, and International Medical Prevention Registry on VTE [IMPROVE] models) were evaluated. Receiver-operating characteristic curves were constructed, and the sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated. In addition, subgroup analyses were performed evaluating the effect of adjunctive pneumatic compression vs none on the study primary outcome. RESULTS: Among 2,003 patients receiving pharmacologic thromboprophylaxis, 198 (9.9%) developed VTE. With multivariable logistic regression analysis, the independent predictors of VTE were Acute Physiology and Chronic Health Evaluation II score, prior immobilization, femoral central venous catheter, and invasive mechanical ventilation. All risk assessment models had areas under the curve < 0.60 except for the Caprini model (0.64; 95% CI, 0.60-0.68). The Caprini, Padua, and Intermountain models had high sensitivity (> 85%) but low specificity (< 20%) for predicting VTE, whereas the ICU-VTE, Kucher, and IMPROVE models had low sensitivities (< 15%) but high specificities (> 85%). The positive predictive value was low (< 20%) for all studied cutoff scores, whereas the negative predictive value was mostly > 90%. Using the risk assessment models to stratify patients into high- vs low-risk subgroups, the effect of adjunctive pneumatic compression vs pharmacologic prophylaxis alone did not differ across the subgroups (Pinteraction > .05). INTERPRETATION: The risk assessment models for VTE performed poorly in patients who are critically ill receiving pharmacologic thromboprophylaxis. None of the models identified a subgroup of patients who might benefit from adjunctive pneumatic compression. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02040103; URL: www. CLINICALTRIALS: gov. ISRCTN44653506.

Population genetics analysis during the elimination process of Plasmodium falciparum in Djibouti.

BACKGROUND: Case management of imported malaria within the context of malaria pre-elimination is increasingly considered to be relevant because of the risk of resurgence. The assessment of malaria importation would provide key data i) to select countries with propitious conditions for pre-elimination phase and ii) to predict its feasibility. Recently, a sero-prevalence study in Djibouti indicated low malaria prevalence, which is propitious for the implementation of pre-elimination, but data on the extent of malaria importation remain unknown. METHODS: Djiboutian plasmodial populations were analysed over an eleven-year period (1998, 1999, 2002 and 2009). The risk of malaria importation was indirectly assessed by using plasmodial population parameters. Based on 5 microsatellite markers, expected heterozygosity (H.e.), multiplicity of infection, pairwise Fst index, multiple correspondence analysis and individual genetic relationship were determined. The prevalence of single nucleotide polymorphisms associated with pyrimethamine resistance was also determined. RESULTS: Data indicated a significant decline in genetic diversity (0.51, 0.59, 0.51 and 0 in 1998, 1999, 2002 and 2009, respectively) over the study period, which is inconsistent with the level of malaria importation described in a previous study. This suggested that Djiboutian malaria situation may have benefited from the decline of malaria prevalence that occurred in neighbouring countries, in particular in Ethiopia. The high Fst indices derived from plasmodial populations from one study period to another (0.12 between 1999 and 2002, and 0.43 between 2002 and 2009) suggested a random sampling of parasites, probably imported from neighbouring countries, leading to oligo-clonal expansion of few different strains during each transmission season. Nevertheless, similar genotypes observed during the study period suggested recurrent migrations and imported malaria. CONCLUSION: In the present study, the extent of genetic diversity was used to assess the risk of malaria importation in the low malaria transmission setting of Djibouti. The molecular approach highlights i) the evolution of Djiboutian plasmodial population profiles that are consistent and compatible with Djiboutian pre-elimination goals and ii) the necessity to implement the monitoring of plasmodial populations and interventions at the regional scale in the Horn of Africa to ensure higher efficiency of malaria control and elimination.

Percent fluid overload for prediction of fluid de-escalation in critically ill patients in Saudi Arabia: a prospective observational study.

BACKGROUND: Percent fluid overload greater than 5% is associated with increased mortality. The appropriate time for fluid deresuscitation depends on the patient's radiological and clinical findings. This study aimed to assess the applicability of percent fluid overload calculations for evaluating the need for fluid deresuscitation in critically ill patients. METHODS: This was a single-center, prospective, observational study of critically ill adult patients requiring intravenous fluid administration. The study's primary outcome was median percent fluid accumulation on the day of fluid deresuscitation or intensive care unit (ICU) discharge, whichever came first. RESULTS: A total of 388 patients was screened between August 1, 2021, and April 30, 2022. Of these, 100 with a mean age of 59.8±16.2 years were included for analysis. The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 15.4±8.0. Sixty-one patients (61.0%) required fluid deresuscitation during their ICU stay, while 39 (39.0%) did not. Median percent fluid accumulation on the day of deresuscitation or ICU discharge was 4.5% (interquartile range [IQR], 1.7%-9.1%) and 5.2% (IQR, 2.9%-7.7%) in patients requiring deresuscitation and those who did not, respectively. Hospital mortality occurred in 25 (40.9%) of patients with deresuscitation and six (15.3%) patients who did not require it (P=0.007). CONCLUSIONS: The percent fluid accumulation on the day of fluid deresuscitation or ICU discharge was not statistically different between patients who required fluid deresuscitation and those who did not. A larger sample size is needed to confirm these findings.

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).

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.

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.

Introducing the Comprehensive Unit-based Safety Program for mechanically ventilated patients in Saudi Arabian Intensive Care Units.

Over the past decade, there have been major improvements to the care of mechanically ventilated patients (MVPs). Earlier initiatives used the concept of ventilator care bundles (sets of interventions), with a primary focus on reducing ventilator-associated pneumonia. However, recent evidence has led to a more comprehensive approach: The ABCDE bundle (Awakening and Breathing trial Coordination, Delirium management and Early mobilization). The approach of the Comprehensive Unit-based Safety Program (CUSP) was developed by patient safety researchers at the Johns Hopkins Hospital and is supported by the Agency for Healthcare Research and Quality to improve local safety cultures and to learn from defects by utilizing a validated structured framework. In August 2015, 17 Intensive Care Units (ICUs) (a total of 271 beds) in eight hospitals in the Kingdom of Saudi Arabia joined the CUSP for MVPs (CUSP 4 MVP) that was conducted in 235 ICUs in 169 US hospitals and led by the Johns Hopkins Armstrong Institute for Patient Safety and Quality. The CUSP 4 MVP project will set the stage for cooperation between multiple hospitals and thus strives to create a countrywide plan for the management of all MVPs in Saudi Arabia.

Determinants of Deescalation Failure in Critically Ill Patients with Sepsis: A Prospective Cohort Study.

Introduction. Deescalation refers to either discontinuation or a step-down of antimicrobials. Despite strong recommendations in the Surviving Sepsis Guidelines (2012) to deescalate, actual practices can vary. Our objective was to identify variables that are associated with deescalation failure. Methods. In this prospective study of patients with sepsis/septic shock, patients were categorized into 4 groups based on antibiotic administration: no change in antibiotics, deescalation, escalation (where antibiotics were changed to those with a broader spectrum of antimicrobial coverage), or mixed changes (where both escalation to a broader spectrum of coverage and discontinuation of antibiotics were carried out). Results. 395 patients were studied; mean APACHE II score was 24 ± 7.8. Antimicrobial deescalation occurred in 189 (48%) patients; no changes were made in 156 (39%) patients. On multivariate regression analysis, failure to deescalate was significantly predicted by hematologic malignancy OR 3.3 (95% CI 1.4-7.4) p < 0.004, fungal sepsis OR 2.7 (95% CI 1.2-5.8) p = 0.011, multidrug resistance OR 2.9 (95% CI 1.4-6.0) p = 0.003, baseline serum procalcitonin OR 1.01 (95% CI 1.003-1.016) p = 0.002, and SAPS II scores OR 1.01 (95% CI 1.004-1.02) p = 0.006. Conclusions. Current deescalation practices reflect physician reluctance when dealing with complicated, sicker patients or with drug-resistance or fungal sepsis. Integrating an antibiotic stewardship program may increase physician confidence and provide support towards increasing deescalation rates.

Measurement of the vascular pedicle width predicts fluid repletion: a cross-sectional comparison with inferior vena cava ultrasound and lung comets.

BACKGROUND: Determination of a patient's volume status remains challenging. Ultrasound assessments of the inferior vena cava and lung parenchyma have been shown to reflect fluid status when compared to the more traditional static and dynamic methods. Yet, resource-limited intensive care units (ICUs) may still not have access to bedside ultrasound. The vascular pedicle width (VPW) measured on chest radiographs remains underutilized for fluid assessment. In this study, we aimed to determine the correlation between ultrasound assessment and vascular pedicle width and to identify a discriminant value that predicted a fluid replete state. METHODS: Eighty-four data points of simultaneous VPW and inferior vena cava measurements were collected on mechanically ventilated patients. VPW measurements were compared with lung comet scores, fluid balance, and a composite variable of inferior vena cava diameter greater than or equal to 2 cm and variability less than 15 %. RESULTS: A VPW of 64 mm accurately predicted fluid repletion with a positive predictive value equal to 88.5 % and an area under the curve (AUC) of 0.843, 95 % CI 0.75-0.93, p < 0.001. VPW closely correlated with inferior vena cava diameter (Pearson's r = 0.64, p = <0.001). Poor correlations were observed between VPW and lung comet score, Pearson's r = 0.12, p = 0.26, fluid balance, Pearson's r = 0.3, p = 0.058, and beta natriuretic peptide, Pearson's r = 0.12, p = 0.26. CONCLUSIONS: This study shows a high predictive ability of the VPW for fluid repletion, as compared to an accepted method of volume assessment. Given the relationship of fluid overload and mortality, these results may assist fluid resuscitation in resource-limited intensive care units.