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.

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.

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.

Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial.

BACKGROUND: Long-term complications of critical illness include intensive care unit (ICU)-acquired weakness and neuropsychiatric disease. Immobilisation secondary to sedation might potentiate these problems. We assessed the efficacy of combining daily interruption of sedation with physical and occupational therapy on functional outcomes in patients receiving mechanical ventilation in intensive care. METHODS: Sedated adults (>/=18 years of age) in the ICU who had been on mechanical ventilation for less than 72 h, were expected to continue for at least 24 h, and who met criteria for baseline functional independence were eligible for enrolment in this randomised controlled trial at two university hospitals. We randomly assigned 104 patients by computer-generated, permuted block randomisation to early exercise and mobilisation (physical and occupational therapy) during periods of daily interruption of sedation (intervention; n=49) or to daily interruption of sedation with therapy as ordered by the primary care team (control; n=55). The primary endpoint-the number of patients returning to independent functional status at hospital discharge-was defined as the ability to perform six activities of daily living and the ability to walk independently. Therapists who undertook patient assessments were blinded to treatment assignment. Secondary endpoints included duration of delirium and ventilator-free days during the first 28 days of hospital stay. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00322010. FINDINGS: All 104 patients were included in the analysis. Return to independent functional status at hospital discharge occurred in 29 (59%) patients in the intervention group compared with 19 (35%) patients in the control group (p=0.02; odds ratio 2.7 [95% CI 1.2-6.1]). Patients in the intervention group had shorter duration of delirium (median 2.0 days, IQR 0.0-6.0 vs 4.0 days, 2.0-8.0; p=0.02), and more ventilator-free days (23.5 days, 7.4-25.6 vs 21.1 days, 0.0-23.8; p=0.05) during the 28-day follow-up period than did controls. There was one serious adverse event in 498 therapy sessions (desaturation less than 80%). Discontinuation of therapy as a result of patient instability occurred in 19 (4%) of all sessions, most commonly for perceived patient-ventilator asynchrony. INTERPRETATION: A strategy for whole-body rehabilitation-consisting of interruption of sedation and physical and occupational therapy in the earliest days of critical illness-was safe and well tolerated, and resulted in better functional outcomes at hospital discharge, a shorter duration of delirium, and more ventilator-free days compared with standard care. FUNDING: None.

Excessive tidal volume from breath stacking during lung-protective ventilation for acute lung injury.

RATIONALE: Low tidal volume ventilation strategies for patients with respiratory failure from acute lung injury may lead to breath stacking and higher volumes than intended. OBJECTIVE: To determine frequency, risk factors, and volume of stacked breaths during low tidal volume ventilation for acute lung injury. DESIGN, SETTING, AND PATIENTS: Prospective cohort study of mechanically ventilated patients with acute lung injury (enrolled from August 2006 through May 2007) treated with low tidal volume ventilation in a medical intensive care unit at an academic tertiary care hospital. INTERVENTIONS: Patients were ventilated with low tidal volumes using the Acute Respiratory Distress Syndrome Network protocol for acute lung injury. Continuous flow-time and pressure-time waveforms were recorded. The frequency, risk factors, and volume of stacked breaths were determined. Sedation depth was monitored using Richmond agitation sedation scale. MEASUREMENTS AND MAIN RESULTS: Twenty patients were enrolled and studied for a mean 3.3 +/- 1.7 days. The median (interquartile range) Richmond agitation sedation scale was -4 (-5, -3). Inter-rater agreement for identifying stacked breaths was high (kappa 0.99, 95% confidence interval 0.98-0.99). Stacked breaths occurred at a mean 2.3 +/- 3.5 per minute and resulted in median volumes of 10.1 (8.8-10.7) mL/kg predicted body weight, which was 1.62 (1.44-1.82) times the set tidal volume. Stacked breaths were significantly less common with higher set tidal volumes (relative risk 0.4 for 1 mL/kg predicted body weight increase in tidal volume, 95% confidence interval 0.23-0.90). CONCLUSION: Stacked breaths occur frequently in low tidal volume ventilation despite deep sedation and result in volumes substantially above the set tidal volume. Set tidal volume has a strong influence on frequency of stacked breaths.

Age-Related Differences in Predictors of Adherence to Rehabilitation After Anterior Cruciate Ligament Reconstruction.

OBJECTIVE: To examine whether the relationships between psychological factors and rehabilitation adherence after knee surgery differ as a function of age. DESIGN AND SETTING: Participants completed inventories of self-motivation, social support, athletic identity, and psychological distress before anterior cruciate ligament (ACL) reconstruction. After surgery, participants recorded their completion of home rehabilitation exercises and cryotherapy, and the sport rehabilitation professionals providing their treatment reported on the patients' attendance at, and adherence during, rehabilitation sessions. SUBJECTS: Sixty-one individuals with acute ACL tears. MEASUREMENTS: The Self-Motivation Inventory, Social Support Inventory, Athletic Identity Measurement Scale, Brief Symptom Inventory, and Sport Injury Rehabilitation Adherence Scale were used to measure self-motivation, social support, athletic identity, psychological distress, and adherence, respectively, during rehabilitation sessions. RESULTS: Hierarchic regression analyses indicated that age moderated the relationships between (1) self-motivation and home exercise completion, (2) social support and home exercise completion, (3) athletic identity and home exercise completion, and (4) athletic identity and home cryotherapy completion. CONCLUSIONS: The prospective moderating relationships for between psychological factors and indices of adherence to home-based rehabilitation activities indicate the need to consider developmental issues when examining psychological aspects of sport-injury rehabilitation.