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Background: Calcium release-activated calcium (CRAC) channel inhibitors block proinflammatory cytokine release, preserve endothelial integrity and may effectively treat patients with severe COVID-19 pneumonia. Methods: CARDEA was a phase 2, randomized, double-blind, placebo-controlled trial evaluating the addition of Auxora, a CRAC channel inhibitor, to corticosteroids and standard of care in adults with severe COVID-19 pneumonia. The primary endpoint was time to recovery through Day 60, with secondary endpoints of all-cause mortality at Day 60 and Day 30. Due to declining rates of COVID-19 hospitalizations and encroachment of prohibited medications as standard of care, the trial was stopped early. Results: The pre-specified efficacy set consisted of the 261 patients with a baseline imputed PaO2/FiO2 £200 with 130 and 131 in the Auxora and placebo groups, respectively. Time to recovery was 7 vs. 10 days (P=0.0979) for patients who received Auxora vs. placebo, respectively. The all-cause mortality rate at Day 60 was 13.8% with Auxora vs. 20.6% with placebo (P=0.1449); Day 30 all-cause mortality was 7.7% and 17.6%, respectively (P=0.0165). Similar trends were noted in patients on high flow nasal cannula at baseline or those with a baseline imputed PaO2/FiO2 ≤100. Serious adverse events occurred less frequently in patients treated with Auxora vs. placebo. Conclusions: Auxora was safe and well tolerated with strong signals in both time to recovery and all-cause mortality through Day 60 in patients with severe COVID-19 pneumonia. Further studies of Auxora in combination with corticosteroids and other immunomodulatory agents are warranted.Trial registration: NCT04345614

Purpose To determine the feasibility of conducting a multicenter ICU RCT of AFS compared to either protocol-directed sedation (PDS) or both PDS and daily sedation interruption (DSI) in North America. Materials and methods This single-center RCT compared AFS [fentanyl (bolus ± infusions) to reach CPOT ≤2; if RASS ≥1, CPOT ≤2 and additional fentanyl failed to reach RASS goal (−2 to 0), low-dose propofol (up to 6 h) was given] with either PDS or both PDS and DSI daily in adults mechanically ventilated (MV) ≥48 h. Relevant feasibility, safety, and clinical outcomes were defined and evaluated. Results 90 of 160 eligible patients were enrolled [AFS = 27; PDS = 28; PDS + DSI = 31]; rate = 3/month. Time from intubation to randomization was 17.5 ± 11.6 h. Study days fully adherent to the study intervention [AFS = 95%; PDS = 99%; PDS + DSI = 96%] and time spent in the first 48 h after randomization without pain (CPOT ≤2)[AFS = 82%; PDS = 78%; PDS + DSI = 77%] and at goal RASS[AFS = 88%; PDS = 83%; PDS + DSI = 95%] were high and similar. Nurse-perceived [median (IQR)] study workload (10-point VAS) was higher with AFS [4(2–6)] than PDS [1(1–3)] or PDS + DSI [2(1–5)]; p = .002). Unplanned extubation was rare (AFS = 1; PDS = 0; PDS + DSI = 1). Days [median (IQR)] free of MV in the 28d after intubation [AFS 24(23,26); PDS 24(20,26); PDS + DSI 24(21,26)] was not different (p = .62). Conclusion A multicenter RCT evaluating AFS is feasible to conduct in North America.

Safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear.What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19?Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated.The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm.Among nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning.ClinicalTrials.gov; No.: NCT04344587; URL: www.gov.

The surge in clinical demand, shortage in personal protective equipment and high-exposure risk for healthcare workers during the COVID-19 pandemic has challenged hospital common practices and forced a reassessment of care delivery models. Code blue teams are highly specialised units that partake in life-saving situations that can jeopardise the safety of team members. There is a paucity of guidance in regards to proper infection control measures to protect the responders.This study describes a methodical approach to assessing vulnerabilities to transmission of SARS-CoV-2 within existing code blue practices, modalities to limit the number of code blue team responders and modifications to the protocol at a large community teaching hospital. The effort undertaken faced challenges due to the nature of the pandemic and the increased demand on healthcare workers. Quality improvement methods facilitated our protocol design and implementation. To this date, there has been no identified COVID-19 disease in any protected code blue (PCB) team members. We recommend that similar practices be considered and adopted widely and practised periodically.

Rationale In critically ill patients receiving invasive mechanical ventilation (MV), research supports the use of daily screening to identify patients who are ready to undergo a spontaneous breathing trial (SBT) followed by conduct of an SBT. However, once daily (OD) screening is poorly aligned with the continuous care provided in most intensive care units (ICUs) and the best SBT technique for clinicians to use remains controversial. Objectives To identify the optimal screening frequency and SBT technique to wean critically ill adults in the ICU. Methods We aim to conduct a multicenter, factorial design randomized controlled trial with concealed allocation, comparing the effect of both screening frequency (once versus at least twice daily [ALTD]) and SBT technique (Pressure Support [PS] + Positive End-Expiratory Pressure [PEEP] vs T-piece) on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American ICUs. In the OD arm, respiratory therapists (RTs) will screen study patients between 06:00 and 08:00 h. In the ALTD arm, patients will be screened at least twice daily between 06:00 and 08:00 h and between 13:00 and 15:00 h with additional screens permitted at the clinician’s discretion. When the SBT screen is passed, an SBT will be conducted using the assigned technique (PS + PEEP or T-piece). We will follow patients until successful extubation, death, ICU discharge, or until day 60 after randomization. We will contact patients or their surrogates six months after randomization to assess health-related quality of life and functional status. Relevance The around-the-clock availability of RTs in North American ICUs presents an important opportunity to identify the optimal SBT screening frequency and SBT technique to minimize patients’ exposure to invasive ventilation and ventilator-related complications. Trial registration Clinical Trials.gov, NCT02399267. Registered on Nov 21, 2016 first registered.

Purpose The purpose was to describe characteristics and outcomes of restrained and nonrestrained patients enrolled in a randomized trial of protocolized sedation compared with protocolized sedation plus daily sedation interruption and to identify patient and treatment factors associated with physical restraint. Methods This was a post hoc secondary analysis using Cox proportional hazards modeling adjusted for center- and time-varying covariates to evaluate predictors of restraint use. Results A total of 328 (76%) of 430 patients were restrained for a median of 4 days. Restrained patients received higher daily doses of benzodiazepines (105 vs 41 mg midazolam equivalent, P μ g fentanyl equivalents, P P P = .02), and more daily benzodiazepine boluses (0.2 vs 0.1, P P = .02) and atypical antipsychotics (17% vs 4%, P = .003). More restrained patients experienced unintentional device removal (26% vs 3%, P P = .01). In the multivariable analysis, alcohol use was associated with decreased risk of restraint (hazard ratio, 0.22; 95% confidence interval, 0.08-0.58). Conclusions Physical restraint was common in mechanically ventilated adults managed with a sedation protocol. Restrained patients received more opioids and benzodiazepines. Except for alcohol use, patient characteristics and treatment factors did not predict restraint use.

To 1) describe factual, emotional, and delusional memories of ICU stay for patients enrolled in the SLEAP (Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol) trial; 2) compare characteristics of patients with and without ICU recall, and patients with and without delusional memories; and 3) determine factors associated with delusional memories 28 days after ICU discharge.Prospective cohort.Sixteen North American medical and surgical ICUs.Critically ill, mechanically ventilated adults randomized in the SLEAP trial.Post-ICU interviews on days 3, 28, and 90 using the validated ICU Memory Tool.Overall, 289 of 297 ICU survivors (97%) (146 protocolized sedation and 143 protocolized sedation plus daily interruption patients) were interviewed at least once. Because there were no differences in recall status or types of memories between the two sedation groups, we present the findings for all patients rather than by study group. On days 3, 28, and 90, 28%, 26%, and 36% of patients, respectively, reported no recall of being in the ICU (overall perception, self-reported) (p = 0.75). Mean daily doses of benzodiazepines and opioids were lower in patients with no ICU recall than those with recall (p0.0001 for both). Despite one third of patients reporting no recall of ICU stay on day 3, 97% and 90% reported at least one factual and one emotional memory from ICU, respectively. Emotional memories declined with time after ICU discharge, particularly panic and confusion. Delusional memories 28 days after discharge were common (70%) yet unrelated to delirium (p = 0.84), recall status (p = 0.15), total dose of benzodiazepine (p = 0.78), or opioid (p = 0.21). Delusional memories were less likely with longer duration of mechanical ventilation (odds ratio, 0.955; 95% CI, 0.91-1.00; p = 0.04).Recall of ICU stay and types of memories reported were not influenced by the trial sedation strategy. Lack of ICU recall and delusional memories were common after ICU discharge despite the use of sedation strategies that promoted wakefulness.

Background:Various intensivist staffing models have been suggested, but the long-term sustainability and outcomes vary and may not be sustained. We examined the impact of implementing a high-intensity intensivist coverage model with a nighttime in-house nocturnist (non-intensivist) and its effect on intensive care unit (ICU) outcomes.Methods:We obtained historical control baseline data from 2007 to 2011 and compared the same data from 2011 to 2015. The Acute Physiological and Chronic Health Evaluation outcomes system was utilized to collect clinical, physiological, and outcome data on all adult patients in the medical ICU and to provide severity-adjusted outcome predictions. The model consists of a mandatory in-house daytime intensivist service that leads multidisciplinary rounds, and an in-house nighttime coverage is provided by nocturnist (nonintensivists) with current procedural skills in airways management, vascular access, and commitment to supervise house staff as needed. The intensivist continues to be available remotely at nighttime for house staff and consultation with the nocturnist. A backup intensivist is available for surge management.Results:First year yielded improved throughput (2428 patients/year to 2627 then 2724 at fifth year). Case mix stable at 53.7 versus 55.2. The ICU length of stay decreased from 4.7 days (predicted 4.25 days) to 3.8 days (4.15) in first year; second year: 3.63 days (4.29 days); third year: 3.24 days (4.37), fourth year: 3.34 days (4.45), and fifth year: 3.61 days (4.42). Intensive care unit 24 hours increased from 4% to 6%. Low-risk monitoring admissions remained at an average 17% (benchmark 17.18%). Intensive care unit mortality improved with standardized mortality ration averaging at 0.84. Resident satisfaction surveys improved.Conclusions:Implementing an intensivist service with nighttime nocturnist staffing in a high-intensity large teaching hospital is feasible and improved ICU outcomes in a sustained manner that persisted after the initial implementation phase. The model resulted in reduced and sustained observed-to-predicted length of ICU stay.

Although numerous studies have shown that anticoagulation of nonvalvular atrial fibrillation (AF) significantly decreases the risk of stroke, anticoagulating critically ill patients in the intensive care unit (ICU) poses many challenges and the benefits have not been determined.To assess the safety and efficacy of anticoagulation in AF patients with sepsis. Ascertaining the incidence of complications associated with anticoagulation therapy, such as bleeding, can optimize patient care.This was a retrospective observational study to assess the incidence of stroke and anticoagulation-related complications (eg, bleeding, heparin-induced thrombocytopenia) in AF patients with severe sepsis. This study was undertaken in a surgical/medical ICU of a teaching, community-based hospital. A total of 115 patients with AF who were admitted with a diagnosis of sepsis were included in the study.Among 115 patients (mean age 81 ± 9.5 years and CHADS2 [congestive heart failure, hypertension, age75 years, diabetes mellitus, stroke] score 3.17 ± 1.20), 80 (69.6%) did not receive anticoagulation treatment during their hospitalization and none of these patients developed a stroke. Anticoagulation-related complications occurred more often in the group who received anticoagulation (8.6% [3/35] vs 0%, P = .008). In the anticoagulated group, a majority of the patients were within therapeutic range less than 50% of the time during their ICU stay. There was no statistically significant difference in survival rates during their hospitalization (66.2% [53/80] for the non-anticoagulated group vs 74.3% [26/35] in the anticoagulated group, P = .392).Administration of anticoagulation for elderly patients with a CHADS2 score at 2 or more in the setting of sepsis can be associated with an increased risk of anticoagulation-related complications (eg, bleeding, heparin-induced thrombocytopenia). Managing and targeting a therapeutic goal with warfarin therapy in critically ill patients with sepsis is challenging. Further studies are necessary to provide appropriate recommendations in this setting.

Background Mechanically ventilated patients may receive more sedation during the night than during the day, potentially delaying extubation. We compared nighttime and daytime benzodiazepine and opioid administration in adult patients enrolled in a multicenter sedation trial comparing protocolized sedation alone or protocolized sedation combined with daily sedation interruption; and we evaluated whether nighttime and daytime doses were associated with liberation from mechanical ventilation. Methods This is a secondary analysis of a randomized trial which was conducted in 16 North American medical-surgical ICUs. In all 423 patients, nurses applied a validated sedation scale hourly to titrate benzodiazepine and opioid infusions to achieve a light level of sedation. Using fentanyl equivalents and midazolam equivalents, we compared dosages administered during night (19:00 to 07:00) and day (07:00 to 19:00) shifts. Using multivariable logistic regression we evaluated the association between nighttime and daytime opioid and sedative doses, and spontaneous breathing trial (SBT) conduct, SBT success, and extubation. Results Nighttime benzodiazepine and opioid doses were significantly higher than daytime doses (mean difference midazolam equivalents 23.3 mg, 95 % CI 12.9, 33.8, p

Background Cardiac dysfunction is one of many causes for unsuccessful weaning from mechanical ventilation. Although cardiac dysfunction can be detected via direct measurement of cardiac output during weaning, available methods are not feasible. Objective To investigate the role of noninvasive monitoring of cardiac output during weaning and determine if a relationship exists between serial measurements during the spontaneous breathing trial and weaning outcomes. Methods A prospective, observational study was conducted in the intensive care unit at a university-affiliated teaching hospital. The sample consisted of patients intubated for more than 24 hours who were being weaned off of mechanical ventilation according to a validated weaning protocol. Before the first spontaneous breathing trial, a noninvasive cardiac output monitor was connected to the ventilator circuit. Measurements were made before, at the beginning of, and at the end of the trial. Results Among the 85 patients tested, baseline cardiac output was similar (P = .93) for those in whom the first trial was successful (mean [SD], 5.7 [2.1] L/min) and those in whom the trial was unsuccessful (5.6 [1.8] L/ min). Unlike patients with unsuccessful trials, patients with successful trials were able to augment their cardiac output from baseline. Mean cardiac output increased to 7.1 (SD, 3.1) L/min for patients in whom weaning was successful and to 6.2 (SD, 2.3) L/min for those in whom weaning was unsuccessful (P = .001). Conclusion A noninvasive method of monitoring cardiac output can be easily applied while patients are being weaned off of mechanical ventilation.

Rationale: Research supports the use of screening protocols to identify patients who are candidates for weaning from mechanical ventilation, and the use of spontaneous breathing trials (SBTs) to predict ability to breathe spontaneously. However, once daily screening is poorly aligned with 24-hour continuous care in the intensive care unit (ICU) environment and the most effective SBT technique is not known. The optimal strategy to liberate our sickest patients from ventilators remains to be determined. Objectives: To assess our ability to recruit critically ill adults and adhere to the screening and SBT protocols. Methods: We propose a pilot, factorial design, randomized trial comparing once-daily versus at least twice daily screening and pressure support (PS) ± positive end-expiratory pressure (PEEP) (inspiratory ± expiratory support) or T-piece (no support) as the SBT technique in critically ill adults who are invasively ventilated for at least 24 hours in 11 North American ICUs. Respiratory Therapists (RTs) will screen all enrolled patients between 06:00 and 08:00 hours daily to identify SBT candidates. Patients in the at least twice daily screening arms will also be screened between 13:00 and 15:00 hours; additional screening will be permitted at clinician’s discretion. Once a screening assessment is passed, an SBT will be conducted with the assigned technique. Outcomes: The study will be considered feasible if at least 1 to 2 patients per ICU per month are recruited and if the screening and SBT protocols are adhered to >80% of the time. Relevance: The availability of RTs in ICUs presents an important opportunity to screen patients more frequently, conduct more frequent SBTs, and reduce the duration of invasive ventilation and ICU stay. FAST Trial Registration: Clinical Trials.gov NCT02399267.

Study objectives: To characterize the frequency, severity, risk factors, and clinician response to propofol-associated hypertriglyceridemia and hypertriglyceridemia-associated pancreatitis. Design: Retrospective analysis. Setting: Medical and surgical intensive care units. Patients: One hundred fifty-nine adult intensive care patients administered propofol for 24 hours or longer and who had at least one serum triglyceride concentration. Measurements and main results: Patient records were reviewed to identify the frequency of hypertriglyceridemia (serum triglyceride concentration > or = 400 mg/dl) and pancreatitis (amylase concentration > or = 125 IU/L, lipase concentration > or = 60 IU/L, and abdominal computed tomography scan or clinical examination findings consistent with pancreatitis). Of the 159 patients, 29 (18%) developed hypertriglyceridemia; six (21%) of the 29 had a serum triglyceride concentration of 1000 mg/dl or greater. The median maximum serum triglyceride concentration was 696 mg/dl (range 403-1737 mg/dl). At the time when hypertriglyceridemia was detected, the median infusion rate of propofol was 50 microg/kg/minute (range 5-110 microg/kg/min). The median time from the start of propofol therapy to identification of hypertriglyceridemia was 54 hours (range 14-319 hrs). Propofol was discontinued within 24 hours of detecting the hypertriglyceridemia 84% of the time. Compared with those who did not develop hypertriglyceridemia, patients who developed hypertriglyceridemia were older, had a longer intensive care unit stay, and received propofol for a longer duration; they were also more likely to be admitted to the medical versus the surgical intensive care unit. Pancreatitis developed in three (10%) of the 29 patients with hypertriglyceridemia. Conclusion: Hypertriglyceridemia and hypertriglyceridemia-associated pancreatitis are often seen in intensive care patients receiving propofol. Serum triglyceride concentrations should be routinely monitored in these patients. In addition, alternative sedation strategies should be considered when hypertriglyceridemia is detected.

Objective: To determine whether diagnosis and bedside observations predict outcomes of patients who have declined intubation but accept noninvasive positive pressure ventilation (NPPV) to treat their respiratory failure. Design: Prospective multiple-center cohort trial. Setting: Two teaching hospitals and two community-based hospitals in southeastern New England from January through October 1999. Patients: All patients receiving NPPV for acute respiratory failure were screened and enrolled if they had a written do-not-intubate (DNI) order. Interventions: Patients were begun on NPPV with mean inspiratory and expiratory pressures of 13.4 ± 0.3 and 5.0 ± 1 cm H2O, respectively. Respiratory therapists recorded demographic information, blood gases, and ventilator type and settings, and they made bedside assessments of cough strength, presence of airway secretions, awake state, and agitation. Patients were followed until discharge for duration of NPPV, survival status, and disposition. Measurements and Main Results: Of 1,211 screened patients, 114 had a DNI status and were enrolled into the study. Of these, 49 (43%) survived to discharge. Age, gender, location in a community vs. teaching hospital, and initial pH and Pao2 did not affect survival, but a higher baseline Paco2 was associated with a favorable odds ratios for survival to discharge. Diagnosis was an important determinant of survival, with congestive heart failure patients having significantly better survival rates than those with chronic obstructive pulmonary disease, cancer, pneumonia, or other diagnoses. A stronger cough and being awake were also associated with increased probability of survival. Conclusion: Patients with respiratory failure and a DNI status have a high overall mortality rate when treated with NPPV, but those with diagnoses such as congestive heart failure or chronic obstructive pulmonary disease, who have a strong cough, or who are awake have better prognoses. These data should be useful when counseling DNI patients and their families on use of NPPV.

Hypersensitivity pneumonitis (HP) is a complex syndrome of varying intensity and clinical presentation, and has been described in association with numerous exposures. Early diagnosis is essential to limit irreversible lung damage. We describe a case of HP in a 42-year-old dry cleaner following occupational exposure to tetrachloroethylene (TCE). The diagnosis was suspected based on clinical presentation and radiographic studies, and confirmed by lung biopsy. A review of the literature reveals that HP has not been reported previously as an occupational lung disease in dry cleaners. We conclude that HP should be suspected in dry cleaners presenting with pulmonary complaints, and TCE should be considered as a potential trigger of disease. The spectrum of TCE-related occupational diseases and the diagnosis of HP are reviewed.

Neurofibromatosis type 1 (NF1)-related lung disease is a rare but increasingly recognised, high morbidity associated feature of the condition. We present a 48-year-old male patient with NF1, who was initially admitted for a subarachnoid haemorrhage requiring aneurysmal coil embolisation. During his recovery, he developed a left-sided pneumothorax requiring chest tube placement followed by concerns for re-expansion pulmonary oedema requiring intubation. Subsequently, the patient also developed a right-sided pneumothorax requiring additional chest tube placement but did not develop right-sided pulmonary oedema. During his hospitalisation, the patient also exemplified other important NF1-related pathophysiology including pheochromocytoma, cerebrovascular abnormalities and cardiovascular manifestations. Due to his multiple comorbidities and poor prognosis, we held a goals of care discussion with the patient's mother, and with her agreement, the patient underwent compassionate withdrawal of artificial life support.

Delirium is common during critical illness and associated with adverse outcomes. We compared characteristics and outcomes of delirious and nondelirious patients enrolled in a multicenter trial comparing protocolized sedation with protocolized sedation plus daily sedation interruption.Randomized trial.Sixteen North American medical and surgical ICUs.Four hundred thirty critically ill, mechanically ventilated adults.All patients had hourly titration of opioid and benzodiazepine infusions using a validated sedation scale. For patients in the interruption group, infusions were resumed, if indicated, at half of previous doses. Delirium screening occurred daily; positive screening was defined as an Intensive Care Delirium Screening Checklist score of 4 or more at any time.Delirium was diagnosed in 226 of 420 assessed patients (53.8%). Coma was identified in 32.7% of delirious compared with 22.7% of nondelirious patients (p = 0.03). The median time to onset of delirium was 3.5 days (interquartile range, 2-7), and the median duration of delirium was 2 days (interquartile range, 1-4). Delirious patients were more likely to be male (61.1% vs 46.6%; p = 0.005), have a surgical/trauma diagnosis (21.2% vs 11.0%; p = 0.030), and history of tobacco (31.5% vs 16.2%; p = 0.002) or alcohol use (34.6% vs 20.9%; p = 0.009). Patients with positive delirium screening had longer duration of ventilation (13 vs 7 d; p0.001), ICU stay (12 vs 8 d; p0.0001), and hospital stay (24 vs 15 d; p0.0001). Delirious patients were more likely to be physically restrained (86.3% vs 76.7%; p = 0.014) and undergo tracheostomy (34.6% vs 15.5%; p0.0001). Antecedent factors independently associated with delirium onset were restraint use (hazard ratio, 1.87; 95% CI, 1.33-2.63; p = 0.0003), antipsychotic administration (hazard ratio, 1.67; 95% CI, 1.005-2.767; p = 0.047), and midazolam dose (hazard ratio, 0.998; 95% CI, 0.997-1.0; p = 0.049). There was no difference in delirium prevalence or duration between the interruption and control groups.In mechanically ventilated adults, delirium was common and associated with longer duration of ventilation and hospitalization. Physical restraint was most strongly associated with delirium.

BACKGROUND Identifying risk factors for unplanned extubation in patients receiving mechanical ventilation can help guide prevention strategies. OBJECTIVE To assess the risk of unplanned extubation with different sedation strategies. METHODS A 36-month quality improvement study in a 33-bed intensive care unit at a tertiary-care center. RESULTS A total of 92 unplanned extubations occurred (7.5 events/1000 days of mechanical ventilation): patients who were receiving continuous sedation protocol with daily interruption of sedatives had 1.5 events/1000 ventilator days, patients receiving the intermittent sedation protocol had 5.0 events/1000 days, and patients with no sedation protocol had 16 events/1000 days (P < .05). Median duration of mechanical ventilation before unplanned extubation was 2 days. Most unplanned extubations (94%) were deliberate, and 53% occurred in patients scheduled for weaning. Most unplanned extubations in the continuous sedation protocol group (71%) occurred during weaning, in comparison to the intermittent sedation protocol (54%) and no sedation protocol groups (48%, P< .05). The highest incidences of agitation were in patients receiving the intermittent sedation protocol as compared with the other 2 groups (77% vs 50% vs 49%, P < .05). Overall, 73% of patients who had an unplanned extubation did not require reintubation; those who did were older (mean age: 68 vs 53 years, P = .01) and were male (80% vs 20%, P= .02). Reintubation was unrelated to the time of unplanned extubation. CONCLUSION Strategies of no sedation or intermittent sedation are both associated with higher rates of unplanned extubation when compared to a strategy of continuous sedation with daily interruption of sedatives. Sedation strategies that allow agitation may increase the risk of unplanned extubation.

Protocolized sedation and daily sedation interruption are 2 strategies to minimize sedation and reduce the duration of mechanical ventilation and intensive care unit (ICU) stay. We hypothesized that combining these strategies would augment the benefits.To compare protocolized sedation with protocolized sedation plus daily sedation interruption in critically ill patients.Randomized controlled trial of 430 critically ill, mechanically ventilated adults conducted in 16 tertiary care medical and surgical ICUs in Canada and the United States between January 2008 and July 2011.Continuous opioid and/or benzodiazepine infusions and random allocation to protocolized sedation (n = 209) (control) or to protocolized sedation plus daily sedation interruption (n = 214). Using validated scales, nurses titrated infusions to achieve light sedation. For patients receiving daily interruption, nurses resumed infusions, if indicated, at half of previous doses. Patients were assessed for delirium and for readiness for unassisted breathing.Time to successful extubation. Secondary outcomes included duration of stay, doses of sedatives and opioids, unintentional device removal, delirium, and nurse and respiratory therapist clinical workload (on a 10-point visual analog scale [VAS]).Median time to successful extubation was 7 days in both the interruption and control groups (median [IQR], 7 [4-13] vs 7 [3-12]; interruption group hazard ratio, 1.08; 95% CI, 0.86-1.35; P = .52). Duration of ICU stay (median [IQR], 10 [5-17] days vs 10 [6-20] days; P = .36) and hospital stay (median [IQR], 20 [10-36] days vs 20 [10-48] days; P = .42) did not differ between the daily interruption and control groups, respectively. Daily interruption was associated with higher mean daily doses of midazolam (102 mg/d vs 82 mg/d; P = .04) and fentanyl (median [IQR], 550 [50-1850] vs 260 [0-1400]; P.001) and more daily boluses of benzodiazepines (mean, 0.253 vs 0.177; P = .007) and opiates (mean, 2.18 vs 1.79; P.001). Unintentional endotracheal tube removal occurred in 10 of 214 (4.7%) vs 12 of 207 patients (5.8%) in the interruption and control groups, respectively (relative risk, 0.82; 95% CI, 0.36-1.84; P = .64). Rates of delirium were not significantly different between groups (53.3% vs 54.1%; relative risk, 0.98; 95% CI, 0.82-1.17; P = .83). Nurse workload was greater in the interruption group (VAS score, 4.22 vs 3.80; mean difference, 0.41; 95% CI, 0.17-0.66; P = .001).For mechanically ventilated adults managed with protocolized sedation, the addition of daily sedation interruption did not reduce the duration of mechanical ventilation or ICU stay.clinicaltrials.gov Identifier: NCT00675363.

Introduction: Atrial fibrillation is a common comorbid condition in patients with severe sepsis admitted to the medical intensive care unit (ICU). While anticoagulation is indicated for moderate to high-risk patients with non-valvular atrial fibrillation (AF) to reduce risk of thromboembolic complications, its benefit in critically ill patients has not been determined. We conducted a study to assess the safety and efficacy of anticoagulation in AF patients with severe sepsis. Methods: A retrospective chart review of 115 patients with AF admitted from February 2004 to February 2009 with a primary diagnosis of sepsis to a teaching community-based hospital was conducted. Medical records were reviewed to confirm AF, determine stroke risk factors (CHAD2) and documented contraindications for anticoagulation. The primary endpoints included stroke and anticoagulation-related bleeding complications before hospital discharge. Results: Amongst 115 patients (mean age 81yrs ± 9.5 and CHAD2 3.17 ± 1.20), the majority of patients 71.3% (82/115) did not receive anticoagulation with a supratherapeutic admission INR>3 being the most common reason for withholding anticoagulation. None of the patients in the non-anticoagulated group developed any embolic events. There was no difference between the anticoagulated and the non-anticoagulated groups in the ICU and hospital length of stay 8.6 days ± 9.1 and 13.6 ± 11.3 vs 7.0 ± 6.7 and 15.6 ± 10.6. Anticoagulation-related complications occurred more often in the anticoagulation group (9.1% [3/33] vs 0%, p = 0.006): these included a nonfatal gastrointestinal bleed (1/33), fatal CNS hemorrhage (1/33), and heparin-induced thrombocytopenia (1/33). In addition, a majority of the patients who received anticoagulation had a therapeutic range achieved in less than 50% of their ICU stay. The two groups had similar hospital survival (64.6% [53/82] for the non-anticoagulated group vs 78.8% [26/33] in the anticoagulated group, p= 0.14). Conclusion: The risk of thromboembolic complications from AF in patients with severe sepsis is exceedingly low and prophylaxis anticoagulation is not warranted. Moreover, a safe anticoagulation range in septic patients is difficult to achieve and is associated with increased risk of bleeding.

Background Although use of sedation protocols and daily sedation interruption (DSI) improve outcome, their current use and barriers affecting their use are unclear. Methods We designed a multidisciplinary, Web-based survey to determine current use of sedation protocols and DSI and the perceived barriers to each, and administered it to members of the Society of Critical Care Medicine. Results The 904 responders were physicians (60%), nurses (14%), or pharmacists (12%); 45% worked in a university hospital. Of 64% having a sedation protocol, 78% used it for ≥50% of ventilated patients. Reasons for lack of protocol use included no physician order (35%), lack of nursing support (11%), and a fear of oversedation (7%). Daily sedation interruption was used by only 40%. Barriers to DSI included lack of nursing acceptance (22%), concern about risk of patient-initiated device removal (19%), and inducement of either respiratory compromise (26%) or patient discomfort (13%). Clinicians who prefer propofol were more likely to use DSI than those who prefer benzodiazepines (55% vs 40, P Conclusions Current intensive care unit sedation practices are heterogeneous, and the barriers preventing the use of both sedation protocols and DSI are numerous. These barriers should be addressed on an institutional basis to boost the use of these evidence-based practices.

Weaning predictors are often incorporated in protocols to predict weaning outcome for patients on mechanical ventilation. The predictors are used as a decision point in protocols to determine whether a patient may advance to a spontaneous breathing trial. The impact of including predictors in a weaning protocol has not been previously studied. We designed a study to determine the effect of including a weaning predictor (frequency-tidal volume ratio, or f/Vt) in a weaning protocol.Randomized, blinded controlled trial.Academic teaching hospitals.Three hundred and four patients admitted to intensive care units at three academic teaching hospitals.Patients were screened daily for measures of oxygenation, cough and secretions, adequate mental status, and hemodynamic stability. Patients were randomized to two groups; in one group the f/Vt was measured but not used in the decision to wean (n = 151), but in the other group, f/Vt was measured and used, using a threshold of 105 breaths/min/L (n = 153). Patients passing the screen received a 2-hr spontaneous breathing trial. Patients passing the spontaneous breathing trial were eligible for an extubation attempt.Groups were similar with regard to gender, age, and Acute Physiology and Chronic Health Evaluation II score. The median duration for weaning time was significantly shorter in the group where the weaning predictor was not used (2.0 vs. 3.0 days, p = .04). There was no difference with regard to the extubation failure, in-hospital mortality rate, tracheostomy, or unplanned extubation.Including a weaning predictor (f/Vt) in a protocol prolonged weaning time. In addition, the predictor did not confer survival benefit or reduce the incidence of extubation failure or tracheostomy. The results of this study indicate that f/Vt should not be used routinely in weaning decision making.

Malaria is one of the most common infectious diseases in the world, and severe respiratory complications have been described mainly in association with Plasmodium falciparum. We describe a case of acute respiratory distress syndrome complicating infection with P. vivax in the setting of relatively low parasitemia in a 47-yr-old woman after a brief trip to Papua New Guinea. A review of the literature shows that pulmonary complications of P. vivax are rare but occur more frequently than generally acknowledged. Pathogenic mechanisms of these complications are discussed.

Venous thromboembolism (VTE) is a spectrum of diseases that can be classified into two categories—deep venous thrombosis (DVT) and pulmonary embolism (PE). The prevalence of VTE is estimated to be 600,000 cases per year, and the mortality rate is 50,000 to 100,000 cases occurring secondary to PE and accounting for 5% to 10% of all hospital deaths in the United States. 5 Although better diagnostic tools have improved the knowledge of the natural history and clinical manifestations of VTE, more than 50% of all cases remain undiagnosed. 5 This occurrence is most likely because of the nonspecificity of signs and symptoms of this disease and the fact that both DVT and PE commonly are unsuspected on clinical grounds and only can be diagnosed with objective testing. 101 In addition, despite many studies that demonstrate the efficacy of preventing DVT and, subsequently, PE, many physicians do not incorporate prophylactic therapy into their daily practice. 6 The specific problems of diagnosis and management of VTE in the ventilated patient in the post acute phase of a severe illness are compounded by several additional factors. Comorbid events contributing to a patient's respiratory symptoms or failure (e.g., exacerbation of chronic obstructive lung disease, pneumonia, or congestive heart failure) frequently can mask the manifestations of VTE. In addition, the nonspecificity of symptoms (e.g., chest pain or dyspnea) and signs (e.g., tachycardia) of a patient on assisted ventilation further contributes to delaying the diagnostic workup for DVT or PE. Finally, the possibility of poor communication between an ill, ventilated patient and the nursing, respiratory, and medical staff caring for this patient can be an additional source of diagnostic confusion. Aside from potential delay in initiating the diagnostic workup for these patients, testing for VTE may be less specific in this context (e.g., perfusion/ventilation scanning in a patient with significant underlying lung disease or pulmonary infiltrates) or technically difficult because of the patient's overall clinical condition. Furthermore, preventive therapy in these patients can be problematic if, for example, there is associated blood dyscrasia or a condition (e.g., gastrointestinal bleed) that prevents anticoagulation. For all of the reasons just mentioned, diagnosis and management of VTE can be challenging particularly in the chronically critically ill patient compared with the patient encountered in an ambulatory setting. This article reviews the general approach to the diagnosis, management, and prevention of VTE, with a focus on the post acute, mechanically ventilated patient. Because of the paucity or absence of specific information derived from clinical trials and related to DVT and PE in this group, recommendations reflect the authors' personal experience and bias, which are derived from working in settings dedicated to treatment of these patients. In discussing the various methods used for the diagnosis of VTE in this patient population, several factors are taken into consideration, including the patient's clinical condition and the availability, feasibility, and cost of a specific test.