Disruption of the circadian rhythm of melatonin: A biomarker of critical illness severity.

Circadian dysrhythmias occur commonly in critically ill patients reflecting variable effects of underlying illness, ICU environment, and treatments. We retrospectively analyzed the relationship between clinical outcomes and 24-h urinary 6-sulfatoxymelatonin (aMT6s) excretion profiles in 37 critically ill patients with shock and/or respiratory failure. Nonlinear regression was used to fit a 24-h cosine curve to each patient's aMT6s profile, with rhythmicity determined by the zero-amplitude test. From these curves we determined acrophase, amplitude, phase, and night/day ratio. After assessing unadjusted relationships, we identified the optimal multivariate models for hospital survival and for discharge to home (vs. death or transfer to another facility). Normalized aMT6s rhythm amplitude was greater (p = 0.005) in patients discharged home than in those who were not, while both groups exhibited a phase delay. Patients with rhythmic aMT6s excretion were more likely to survive (OR 5.25) and be discharged home (OR 8.89; p < 0.05 for both) than patients with arrhythmic profiles, associations that persisted in multivariate modelling. In critically ill patients with shock and/or respiratory failure, arrhythmic and/or low amplitude 24-h aMT6s rhythms were associated with worse clinical outcomes, suggesting a role for the melatonin-based rhythm as a novel biomarker of critical illness severity.

Effect of early mobilisation on long-term cognitive impairment in critical illness in the USA: a randomised controlled trial.

BACKGROUND: Patients who have received mechanical ventilation can have prolonged cognitive impairment for which there is no known treatment. We aimed to establish whether early mobilisation could reduce the rates of cognitive impairment and other aspects of disability 1 year after critical illness. METHODS: In this single-centre, parallel, randomised controlled trial, patients admitted to the adult medical-surgical intensive-care unit (ICU), at the University of Chicago (IL, USA), were recruited. Inclusion criteria were adult patients (aged ≥18 years) who were functionally independent and mechanically ventilated at baseline and within the first 96 h of mechanical ventilation, and expected to continue for at least 24 h. Patients were randomly assigned (1:1) via computer-generated permuted balanced block randomisation to early physical and occupational therapy (early mobilisation) or usual care. An investigator designated each assignment in consecutively numbered, sealed, opaque envelopes; they had no further involvement in the trial. Only the assessors were masked to group assignment. The primary outcome was cognitive impairment 1 year after hospital discharge, measured with a Montreal Cognitive Assessment. Patients were assessed for cognitive impairment, neuromuscular weakness, institution-free days, functional independence, and quality of life at hospital discharge and 1 year. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov, number NCT01777035, and is now completed. FINDINGS: Between Aug 11, 2011, and Oct 24, 2019, 1222 patients were screened, 200 were enrolled (usual care n=100, intervention n=100), and one patient withdrew from the study in each group; thus 99 patients in each group were included in the intention-to-treat analysis (113 [57%] men and 85 [43%] women). 65 (88%) of 74 in the usual care group and 62 (89%) of 70 in the intervention group underwent testing for cognitive impairment at 1 year. The rate of cognitive impairment at 1 year with early mobilisation was 24% (24 of 99 patients) compared with 43% (43 of 99) with usual care (absolute difference -19·2%, 95% CI -32·1 to -6·3%; p=0·0043). Cognitive impairment was lower at hospital discharge in the intervention group (53 [54%] 99 patients vs 68 [69%] 99 patients; -15·2%, -28·6 to -1·7; p=0·029). At 1 year, the intervention group had fewer ICU-acquired weaknesses (none [0%] of 99 patients vs 14 [14%] of 99 patients; -14·1%; -21·0 to -7·3; p=0·0001) and higher physical component scores on quality-of-life testing than did the usual care group (median 52·4 [IQR 45·3-56·8] vs median 41·1 [31·8-49·4]; p<0·0001). There was no difference in the rates of functional independence (64 [65%] of 99 patients vs 61 [62%] of 99 patients; 3%, -10·4 to 16·5%; p=0·66) or mental component scores (median 55·9 [50·2-58·9] vs median 55·2 [49·5-59·7]; p=0·98) between the intervention and usual care groups at 1 year. Seven adverse events (haemodynamic changes [n=3], arterial catheter removal [n=1], rectal tube dislodgement [n=1], and respiratory distress [n=2]) were reported in six (6%) of 99 patients in the intervention group and in none of the patients in the usual care group (p=0·029). INTERPRETATION: Early mobilisation might be the first known intervention to improve long-term cognitive impairment in ICU survivors after mechanical ventilation. These findings clearly emphasise the importance of avoiding delays in initiating mobilisation. However, the increased adverse events in the intervention group warrants further investigation to replicate these findings. FUNDING: None.

Immunomodulatory fecal metabolites are associated with mortality in COVID-19 patients with respiratory failure.

Respiratory failure and mortality from COVID-19 result from virus- and inflammation-induced lung tissue damage. The intestinal microbiome and associated metabolites are implicated in immune responses to respiratory viral infections, however their impact on progression of severe COVID-19 remains unclear. We prospectively enrolled 71 patients with COVID-19 associated critical illness, collected fecal specimens within 3 days of medical intensive care unit admission, defined microbiome compositions by shotgun metagenomic sequencing, and quantified microbiota-derived metabolites (NCT #04552834). Of the 71 patients, 39 survived and 32 died. Mortality was associated with increased representation of Proteobacteria in the fecal microbiota and decreased concentrations of fecal secondary bile acids and desaminotyrosine (DAT). A microbiome metabolic profile (MMP) that accounts for fecal secondary bile acids and desaminotyrosine concentrations was independently associated with progression of respiratory failure leading to mechanical ventilation. Our findings demonstrate that fecal microbiota composition and microbiota-derived metabolite concentrations can predict the trajectory of respiratory function and death in patients with severe SARS-Cov-2 infection and suggest that the gut-lung axis plays an important role in the recovery from COVID-19.

Immediate Effect of Mechanical Ventilation Mode and Sedative Infusion on Measured Diaphragm Thickness.

Rationale: In patients who are mechanically ventilated, diaphragm thinning on ultrasound is thought to correlate with diaphragm atrophy and has been associated with prolonged intubation. Factors other than atrophy, however, may cause changes in diaphragm thickness, which may confound studies examining changes in diaphragm thickness over time. Objectives: To determine if changes in the mode of mechanical ventilation or an interruption of sedatives have immediate effects on diaphragm thickness measurements in adult patients in the intensive care unit who are mechanically ventilated. Methods: Adult patients receiving invasive mechanical ventilation for less than 48 hours were included. Diaphragm thickness was measured at end-expiration and peak inspiration using ultrasound while patients were receiving both volume assist-control and pressure-support modes in a randomized crossover fashion. In patients receiving sedatives, additional measurements were taken after an interruption of sedatives. Measurements were compared between modes and on assist-control before and after an interruption of sedatives. Results: Of 85 patients enrolled, 66 had measurements on assist-control and spontaneous modes, and 40 had measurements before and after an interruption of sedatives. End-expiratory diaphragm thickness increased by a median of 0.08 mm after an interruption of sedatives (95% confidence interval [CI], 0.002 mm to 0.164 mm; P = 0.017), corresponding to a median increase of 6.5%. No difference was seen when comparing measurements taken on volume assist-control and pressure support (median difference, 0 mm; 95% CI, -0.07 mm to 0.08 mm; P = 0.98). Conclusions: End-expiratory diaphragm thickness increased by 6.5% after an interruption of sedatives. The effect of sedatives on measured diaphragm thickness should be considered in future studies examining changes in diaphragm thickness over time. Clinical trial registered with Clinicaltrials.gov (NCT04319939).

Bedside estimates of dead space using end-tidal CO2 are independently associated with mortality in ARDS.

PURPOSE: In acute respiratory distress syndrome (ARDS), dead space fraction has been independently associated with mortality. We hypothesized that early measurement of the difference between arterial and end-tidal CO2 (arterial-ET difference), a surrogate for dead space fraction, would predict mortality in mechanically ventilated patients with ARDS. METHODS: We performed two separate exploratory analyses. We first used publicly available databases from the ALTA, EDEN, and OMEGA ARDS Network trials (N = 124) as a derivation cohort to test our hypothesis. We then performed a separate retrospective analysis of patients with ARDS using University of Chicago patients (N = 302) as a validation cohort. RESULTS: The ARDS Network derivation cohort demonstrated arterial-ET difference, vasopressor requirement, age, and APACHE III to be associated with mortality by univariable analysis. By multivariable analysis, only the arterial-ET difference remained significant (P = 0.047). In a separate analysis, the modified Enghoff equation ((PaCO2-PETCO2)/PaCO2) was used in place of the arterial-ET difference and did not alter the results. The University of Chicago cohort found arterial-ET difference, age, ventilator mode, vasopressor requirement, and APACHE II to be associated with mortality in a univariate analysis. By multivariable analysis, the arterial-ET difference continued to be predictive of mortality (P = 0.031). In the validation cohort, substitution of the arterial-ET difference for the modified Enghoff equation showed similar results. CONCLUSION: Arterial to end-tidal CO2 (ETCO2) difference is an independent predictor of mortality in patients with ARDS.

Characteristics of Critically Ill Adults With Sacrococcygeal Unavoidable Hospital-Acquired Pressure Injuries: A Retrospective, Matched, Case-Control Study.

PURPOSE: To identify characteristics of critically ill adults with sacrococcygeal, unavoidable hospital-acquired pressure injuries (uHAPIs). DESIGN: Retrospective, matched, case-control design. SUBJECTS/SETTING: Patients admitted to adult intensive care units (ICUs) at an urban academic medical center from January 2014 through July 2016. METHODS: Thirty-four patients without uHAPI were matched to 34 patients with sacrococcygeal uHAPI. Time points of interest included admission to the ICU, the week preceding the definitive assessment date, and hospital discharge status. Variables of interest included length of stay, any diagnosis of sepsis, severity of illness, degree of organ dysfunction/failure, supportive therapies in use (eg, mechanical ventilation), and pressure injury risk (Braden Scale score). RESULTS: All 34 sacrococcygeal pressure injuries were classified as uHAPI using the pressure injury prevention inventory instrument. No statistically significant differences were noted between patients for severity of illness, degree of organ dysfunction/failure, or pressure injury risk at ICU admission. At 1 day prior to the definitive assessment date and at discharge, patients with uHAPI had significantly higher mean Sequential Organ Failure Assessment (SOFA) scores (greater organ dysfunction/failure) and lower mean Braden Scale scores (greater pressure injury risk) than patients without uHAPI. Patients with uHAPI had significantly longer lengths of stay, more supportive therapies in use, were more often diagnosed with sepsis, and were more likely to die during hospitalization. CONCLUSION: Sacrococcygeal uHAPI development was associated with progressive multiorgan dysfunction/failure, greater use of supportive therapies, sepsis diagnosis, and mortality. Additional research investigating the role of multiorgan dysfunction/failure and sepsis on uHAPI development is warranted.

Impact of Vasoactive Medications on ICU-Acquired Weakness in Mechanically Ventilated Patients.

BACKGROUND: Vasoactive medications are commonly used in the treatment of critically ill patients, but their impact on the development of ICU-acquired weakness is not well described. The objective of this study is to evaluate the relationship between vasoactive medication use and the outcome of ICU-acquired weakness. METHODS: This is a secondary analysis of mechanically ventilated patients (N = 172) enrolled in a randomized clinical trial of early occupational and physical therapy vs conventional therapy, which evaluated the end point of ICU-acquired weakness on hospital discharge. Patients underwent bedside muscle strength testing by a therapist blinded to study allocation to evaluate for ICU-acquired weakness. The effects of vasoactive medication use on the incidence of ICU-acquired weakness in this population were assessed. RESULTS: On logistic regression analysis, the use of vasoactive medications increased the odds of developing ICU-acquired weakness (odds ratio [OR], 3.2; P = .01) independent of all other established risk factors for weakness. Duration of vasoactive medication use (in days) (OR, 1.35; P = .004) and cumulative norepinephrine dose (µg/kg/d) (OR, 1.01; P = .02) (but not vasopressin or phenylephrine) were also independently associated with the outcome of ICU-acquired weakness. CONCLUSIONS: In mechanically ventilated patients enrolled in a randomized clinical trial of early mobilization, the use of vasoactive medications was independently associated with the development of ICU-acquired weakness. Prospective trials to further evaluate this relationship are merited. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01777035; URL: www.clinicaltrials.gov.

Comparison of Two Lidocaine Administration Techniques on Perceived Pain From Bedside Procedures: A Randomized Clinical Trial.

BACKGROUND: Lidocaine is used to alleviate procedural pain but paradoxically increases pain during injection. Pain perception can be modulated by non-noxious stimuli such as temperature or touch according to the gate control theory of pain. We postulated that lidocaine dripped onto the skin prior to injection would cool or add the sensation of touch at the skin surface to reduce pain perception from the procedure. METHODS: A randomized clinical trial of patients referred to the procedure service from February 2011 through March 2015 was conducted. All patients received 1% subcutaneous lidocaine injection. Patients randomized to the intervention group had approximately 1 to 2 ml of lidocaine squirted onto the skin surface prior to subcutaneous lidocaine injection. Patients were blinded to the details of the intervention and were surveyed by a blinded investigator to document the primary outcome (severity of pain from the procedure) using a visual analog scale. RESULTS: A total of 481 patients provided consent and were randomized to treatment. There was a significant improvement in the primary outcome of procedural pain (control, 16.6 ± 24.8 mm vs 12.2 ± 19.4 mm; P = .03) with the intervention group as assessed by using the visual analog scale score. Pain scores were primarily improved for peripherally inserted central catheters (control, 18.8 ± 25.6 mm vs 12.2 ± 18.2 mm; P = .02) upon subgroup analysis. CONCLUSIONS: Bedside procedures are exceedingly common. Data regarding the severity of procedural pain and strategies to mitigate it are important for the informed consent process and patient satisfaction. Overall, pain reported from common bedside procedures is low, but pain can be further reduced with the addition of lidocaine onto the skin surface to modulate pain perception. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01330134; URL: www.clinicaltrials.gov.

One-Year Outcomes in Patients With Acute Respiratory Distress Syndrome Enrolled in a Randomized Clinical Trial of Helmet Versus Facemask Noninvasive Ventilation.

OBJECTIVES: Many survivors of acute respiratory distress syndrome have poor long-term outcomes possibly due to supportive care practices during "invasive" mechanical ventilation. Helmet noninvasive ventilation in acute respiratory distress syndrome may reduce intubation rates; however, it is unknown if avoiding intubation with helmet noninvasive ventilation alters the consequences of surviving acute respiratory distress syndrome. DESIGN: Long-term follow-up data from a previously published randomized controlled trial. PATIENTS: Adults patients with acute respiratory distress syndrome enrolled in a previously published clinical trial. SETTING: Adult ICU. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was functional independence at 1 year after hospital discharge defined as independence in activities of daily living and ambulation. At 1 year, patients were surveyed to assess for functional independence, survival, and number of institution-free days, defined as days alive spent living at home. The presence of ICU-acquired weakness and functional independence was also assessed by a blinded therapist on hospital discharge. On hospital discharge, there was a greater prevalence of ICU-acquired weakness (79.5% vs 38.6%; p = 0.0002) and less functional independence (15.4% vs 50%; p = 0.001) in the facemask group. One-year follow-up data were collected for 81 of 83 patients (97.6%). One-year mortality was higher in the facemask group (69.2% vs 43.2%; p = 0.017). At 1 year, patients in the helmet group were more likely to be functionally independent (40.9% vs 15.4%; p = 0.015) and had more institution-free days (median, 268.5 [0-354] vs 0 [0-323]; p = 0.017). CONCLUSIONS: Poor functional recovery after invasive mechanical ventilation for acute respiratory distress syndrome is common. Helmet noninvasive ventilation may be the first intervention that mitigates the long-term complications that plague survivors of acute respiratory distress syndrome managed with noninvasive ventilation.

Clinical Practice Guideline: Safe Medication Use in the ICU.

OBJECTIVE: To provide ICU clinicians with evidence-based guidance on safe medication use practices for the critically ill. DATA SOURCES: PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, Scopus, and ISI Web of Science for relevant material to December 2015. STUDY SELECTION: Based on three key components: 1) environment and patients, 2) the medication use process, and 3) the patient safety surveillance system. The committee collectively developed Population, Intervention, Comparator, Outcome questions and quality of evidence statements pertaining to medication errors and adverse drug events addressing the key components. A total of 34 Population, Intervention, Comparator, Outcome questions, five quality of evidence statements, and one commentary on disclosure was developed. DATA EXTRACTION: Subcommittee members were assigned selected Population, Intervention, Comparator, Outcome questions or quality of evidence statements. Subcommittee members completed their Grading of Recommendations Assessment, Development, and Evaluation of the question with his/her quality of evidence assessment and proposed strength of recommendation, then the draft was reviewed by the relevant subcommittee. The subcommittee collectively reviewed the evidence profiles for each question they developed. After the draft was discussed and approved by the entire committee, then the document was circulated among all members for voting on the quality of evidence and strength of recommendation. DATA SYNTHESIS: The committee followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation system to determine quality of evidence and strength of recommendations. CONCLUSIONS: This guideline evaluates the ICU environment as a risk for medication-related events and the environmental changes that are possible to improve safe medication use. Prevention strategies for medication-related events are reviewed by medication use process node (prescribing, distribution, administration, monitoring). Detailed considerations to an active surveillance system that includes reporting, identification, and evaluation are discussed. Also, highlighted is the need for future research for safe medication practices that is specific to critically ill patients.

Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.

IMPORTANCE: Noninvasive ventilation (NIV) with a face mask is relatively ineffective at preventing endotracheal intubation in patients with acute respiratory distress syndrome (ARDS). Delivery of NIV with a helmet may be a superior strategy for these patients. OBJECTIVE: To determine whether NIV delivered by helmet improves intubation rate among patients with ARDS. DESIGN, SETTING, AND PARTICIPANTS: Single-center randomized clinical trial of 83 patients with ARDS requiring NIV delivered by face mask for at least 8 hours while in the medical intensive care unit at the University of Chicago between October 3, 2012, through September 21, 2015. INTERVENTIONS: Patients were randomly assigned to continue face mask NIV or switch to a helmet for NIV support for a planned enrollment of 206 patients (103 patients per group). The helmet is a transparent hood that covers the entire head of the patient and has a rubber collar neck seal. Early trial termination resulted in 44 patients randomized to the helmet group and 39 to the face mask group. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who required endotracheal intubation. Secondary outcomes included 28-day invasive ventilator-free days (ie, days alive without mechanical ventilation), duration of ICU and hospital length of stay, and hospital and 90-day mortality. RESULTS: Eighty-three patients (45% women; median age, 59 years; median Acute Physiology and Chronic Health Evaluation [APACHE] II score, 26) were included in the analysis after the trial was stopped early based on predefined criteria for efficacy. The intubation rate was 61.5% (n = 24) for the face mask group and 18.2% (n = 8) for the helmet group (absolute difference, -43.3%; 95% CI, -62.4% to -24.3%; P < .001). The number of ventilator-free days was significantly higher in the helmet group (28 vs 12.5, P < .001). At 90 days, 15 patients (34.1%) in the helmet group died compared with 22 patients (56.4%) in the face mask group (absolute difference, -22.3%; 95% CI, -43.3 to -1.4; P = .02). Adverse events included 3 interface-related skin ulcers for each group (ie, 7.6% in the face mask group had nose ulcers and 6.8% in the helmet group had neck ulcers). CONCLUSIONS AND RELEVANCE: Among patients with ARDS, treatment with helmet NIV resulted in a significant reduction of intubation rates. There was also a statistically significant reduction in 90-day mortality with helmet NIV. Multicenter studies are needed to replicate these findings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01680783.

Impact of early mobilization on glycemic control and ICU-acquired weakness in critically ill patients who are mechanically ventilated.

BACKGROUND: ICU-acquired weakness (ICU-AW) has immediate and long-term consequences for critically ill patients. Strategies for the prevention of weakness include modification of known risk factors, such as hyperglycemia and immobility. Intensive insulin therapy (IIT) has been proposed to prevent critical illness polyneuropathy. However, the effect of insulin and early mobilization on clinically apparent weakness is not well known. METHODS: This is a secondary analysis of all patients with mechanical ventilation (N = 104) previously enrolled in a randomized controlled trial of early occupational and physical therapy vs conventional therapy, which evaluated the end point of functional independence. Every patient had IIT and blinded muscle strength testing on hospital discharge to determine the incidence of clinically apparent weakness. The effects of insulin dose and early mobilization on the incidence of ICU-AW were assessed. RESULTS: On logistic regression analyses, early mobilization and increasing insulin dose prevented the incidence of ICU-AW (OR, 0.18, P = .001; OR, 0.001, P = .011; respectively) independent of known risk factors for weakness. Early mobilization also significantly reduced insulin requirements to achieve similar glycemic goals as compared with control patients (0.07 units/kg/d vs 0.2 units/kg/d, P < .001). CONCLUSIONS: The duel effect of early mobilization in reducing clinically relevant ICU-AW and promoting euglycemia suggests its potential usefulness as an alternative to IIT.

Multiprofessional survey of protocol use in the intensive care unit.

PURPOSE: To date, there has been no large multicenter, multiprofessional evaluation of protocol and guideline use in the intensive care unit (ICU). The primary purpose of this study was to describe national availability, development, implementation, and assessment of protocols in ICUs. A secondary objective was to compare perceived utility by ease of use, patient safety, cost containment, and compliance of protocols between nurses, physicians, and pharmacists. MATERIALS AND METHODS: The survey was developed and tested for validity by 15 clinicians who identified additional domains of interest. An additional 15 clinicians of the 3 different professions evaluated the survey for relevancy and appropriateness of responses. Three survey experts evaluated survey construction. The survey was uploaded to a Web survey tool and pilot tested for clarity and ease of completion. RESULTS: The overall response rate for the survey was 18.1% (n = 614). Popular methods of education for protocol implementation included staff meetings (85.3%) and unit-specific in-services (77.7%). Protocols were most often updated when new information was available (40.8%) or every 12 months (17.9%). The most common limitation to development and implementation was limited personnel resources (24.5%) and physicians not wanting to use them (21.3%), respectively. Clinicians indicated that protocols made their job easier and improved cost containment some or most of the time. Sepsis protocols were identified as most useful in promoting patient outcomes by all 3 professions. CONCLUSIONS: The types of protocols available appear to be those assisting with management of high-alert medications. Overcoming the perceived barriers of protocol use within ICUs requires personnel for development and physician support. A better protocol review process may be necessary to assure optimal content, desired outcomes, and consistency with Institute for Safe Medication Practices guidelines.

Temporal disorganization of circadian rhythmicity and sleep-wake regulation in mechanically ventilated patients receiving continuous intravenous sedation.

OBJECTIVES: Sleep is regulated by circadian and homeostatic processes and is highly organized temporally. Our study was designed to determine whether this organization is preserved in patients receiving mechanical ventilation (MV) and intravenous sedation. DESIGN: Observational study. SETTING: Academic medical intensive care unit. PATIENTS: Critically ill patients receiving MV and intravenous sedation. METHODS: Continuous polysomnography (PSG) was initiated an average of 2.0 (1.0, 3.0) days after ICU admission and continued ≥ 36 h or until the patient was extubated. Sleep staging and power spectral analysis were performed using standard approaches. We also calculated the electroencephalography spectral edge frequency 95% SEF95, a parameter that is normally higher during wakefulness than during sleep. Circadian rhythmicity was assessed in 16 subjects through the measurement of aMT6s in urine samples collected hourly for 24-48 hours. Light intensity at the head of the bed was measured continuously. MEASUREMENTS AND RESULTS: We analyzed 819.7 h of PSG recordings from 21 subjects. REM sleep was identified in only 2/21 subjects. Slow wave activity lacked the normal diurnal and ultradian periodicity and homeostatic decline found in healthy adults. In nearly all patients, SEF95 was consistently low without evidence of diurnal rhythmicity (median 6.3 [5.3, 7.8] Hz, n = 18). A circadian rhythm of aMT6s excretion was present in most (13/16, 81.3%) patients, but only 4 subjects had normal timing. Comparison of the SEF95 during the melatonin-based biological night and day revealed no difference between the 2 periods (P = 0.64). CONCLUSIONS: The circadian rhythms and PSG of patients receiving mechanical ventilation and intravenous sedation exhibit pronounced temporal disorganization. The finding that most subjects exhibited preserved, but phase delayed, excretion of aMT6s suggests that the circadian pacemaker of such patients may be free-running.

Patient-related factors associated with hospital discharge to a care facility after critical illness.

BACKGROUND: Many critically ill patients are transferred to other care facilities instead of to home at hospital discharge. OBJECTIVE: To identify patient-related factors associated with hospital discharge to a care facility after critical illness and to estimate the magnitude of risk associated with each factor. METHODS: Retrospective cohort study of 548 survivors of critical illness in a medical intensive care unit. Multivariable logistic regression was used to identify independent risk factors for discharge to a care facility. Only the first 72 hours of intensive care were analyzed. RESULTS: Approximately one-quarter of the survivors of critical illness were discharged to a care facility instead of to home. This event occurred more commonly in older patients, even after adjustment for severity of illness and comorbid conditions (odds ratio [OR] 1.8 for patients ≥ 65 years of age vs patients < 65 years; 95% confidence interval [CI], 1.1-3.1; P = .02). The risk was greatest for patients who received mechanical ventilation (OR, 3.4; 95% CI, 2.0-5.8; P < .001) or had hospitalizations characterized by severe cognitive dysfunction (OR, 8.1; 95% CI, 1.3-50.6; P = .02) or poor strength and/or mobility (OR, 31.7; 95% CI, 6.4-157.3; P < .001). The model showed good discrimination (area under the curve, 0.82; 95% CI, 0.77-0.86). CONCLUSION: The model, which did not include baseline function or social variables, provided good discrimination between patients discharged to a care facility after critical illness and patients discharged to home. These results suggest that future research should focus on the debilitating effects of respiratory failure and on conditions with cognitive and neuromuscular sequelae.

Feasibility of physical and occupational therapy beginning from initiation of mechanical ventilation.

OBJECTIVE: Physical and occupational therapy are possible immediately after intubation in mechanically ventilated medical intensive care unit patients. The objective of this study was to describe a protocol of daily sedative interruption and early physical and occupational therapy and to specify details of intensive care unit-based therapy, including neurocognitive state, potential barriers, and adverse events related to this intervention. DESIGN AND PATIENTS: Detailed descriptive study of the intervention arm of a trial of mechanically ventilated patients receiving early physical and occupational therapy. SETTING: Two tertiary care academic medical centers participating in a randomized controlled trial. INTERVENTION: Patients underwent daily sedative interruption followed by physical and occupational therapy every hospital day until achieving independent functional status. Therapy began with active range of motion and progressed to activities of daily living, sitting, standing, and walking as tolerated. MEASUREMENTS AND MAIN RESULTS: Forty-nine mechanically ventilated patients received early physical and occupational therapy occurring a median of 1.5 days (range, 1.0-2.1 days) after intubation. Therapy was provided on 90% of MICU days during mechanical ventilation. While endotracheally intubated, subjects sat at the edge of the bed in 69% of all physical and occupational therapy sessions, transferred from bed to chair in 33%, stood in 33%, and ambulated during 15% (n = 26 of 168) of all physical and occupational therapy sessions (median distance of 15 feet; range, 15-20 feet). At least one potential barrier to mobilization during mechanical ventilation (acute lung injury, vasoactive medication administration, delirium, renal replacement therapy, or body mass index ≥ 30 kg/m) was present in 89% of patient encounters. Therapy was interrupted prematurely in 4% of all sessions, most commonly for patient-ventilator asynchrony and agitation. CONCLUSION: Early physical and occupational therapy is feasible from the onset of mechanical ventilation despite high illness acuity and presence of life support devices. Adverse events are uncommon, even in this high-risk group.