Anne S. Pohlman

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.

Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial.

BACKGROUND Approaches to removal of sedation and mechanical ventilation for critically ill patients vary widely. Our aim was to assess a protocol that paired spontaneous awakening trials (SATs)-ie, daily interruption of sedatives-with spontaneous breathing trials (SBTs). METHODS In four tertiary-care hospitals, we randomly assigned 336 mechanically ventilated patients in intensive care to management with a daily SAT followed by an SBT (intervention group; n=168) or with sedation per usual care plus a daily SBT (control group; n=168). The primary endpoint was time breathing without assistance. Data were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00097630. FINDINGS One patient in the intervention group did not begin their assigned treatment protocol because of withdrawal of consent and thus was excluded from analyses and lost to follow-up. Seven patients in the control group discontinued their assigned protocol, and two of these patients were lost to follow-up. Patients in the intervention group spent more days breathing without assistance during the 28-day study period than did those in the control group (14.7 days vs 11.6 days; mean difference 3.1 days, 95% CI 0.7 to 5.6; p=0.02) and were discharged from intensive care (median time in intensive care 9.1 days vs 12.9 days; p=0.01) and the hospital earlier (median time in the hospital 14.9 days vs 19.2 days; p=0.04). More patients in the intervention group self-extubated than in the control group (16 patients vs six patients; 6.0% difference, 95% CI 0.6% to 11.8%; p=0.03), but the number of patients who required reintubation after self-extubation was similar (five patients vs three patients; 1.2% difference, 95% CI -5.2% to 2.5%; p=0.47), as were total reintubation rates (13.8%vs 12.5%; 1.3% difference, 95% CI -8.6% to 6.1%; p=0.73). At any instant during the year after enrolment, patients in the intervention group were less likely to die than were patients in the control group (HR 0.68, 95% CI 0.50 to 0.92; p=0.01). For every seven patients treated with the intervention, one life was saved (number needed to treat was 7.4, 95% CI 4.2 to 35.5). INTERPRETATION Our results suggest that a wake up and breathe protocol that pairs daily spontaneous awakening trials (ie, interruption of sedatives) with daily spontaneous breathing trials results in better outcomes for mechanically ventilated patients in intensive care than current standard approaches and should become routine practice.

Daily interruption of sedative infusions and complications of critical illness in mechanically ventilated patients.

Objective:In critically ill patients receiving mechanical ventilation, daily interruption of sedative infusions decreases duration of mechanical ventilation and intensive care unit length of stay. Whether this sedation strategy reduces the incidence of complications commonly associated with critical illness is not known. Design:Blinded, retrospective chart review. Setting:University-based hospital in Chicago, IL. Patients:One hundred twenty-eight patients receiving mechanical ventilation and continuous infusions of sedative drugs in a medical intensive care unit. Interventions:None. Measurements and Main Results:We performed a blinded, retrospective evaluation of the database from our previous trial of 128 patients randomized to daily interruption of sedative infusions vs. sedation as directed by the medical intensive care unit team without this strategy. Seven distinct complications associated with mechanical ventilation and critical illness were identified: a) ventilator-associated pneumonia; b) upper gastrointestinal hemorrhage; c) bacteremia; d) barotrauma; e) venous thromboembolic disease; and f) cholestasis or g) sinusitis requiring surgical intervention. The incidence of complications was evaluated for each patient’s hospital course.One hundred twenty-six of 128 charts were available for review. Patients undergoing daily interruption of sedative infusions experienced 13 complications (2.8%) vs. 26 (6.2%) in those subjected to conventional sedation techniques (p = .04). Conclusions:Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation reduces intensive care unit length of stay and, in turn, decreases the incidence of complications of critical illness associated with prolonged intubation and mechanical ventilation.

A randomized trial of intermittent lorazepam versus propofol with daily interruption in mechanically ventilated patients.

Objective:To compare duration of mechanical ventilation for patients randomized to receive lorazepam by intermittent bolus administration vs. continuous infusions of propofol using protocols that include scheduled daily interruption of sedation. Design:A randomized open-label trial enrolling patients from October 2001 to March 2004. Setting:Medical intensive care units of two tertiary care medical centers. Patients:Adult patients expected to require mechanical ventilation for >48 hrs and who required ≥10 mg of lorazepam or a continuous infusion of a sedative to achieve adequate sedation. Interventions:Patients were randomized to receive lorazepam by intermittent bolus administration or propofol by continuous infusion to maintain a Ramsay score of 2–3. Sedation was interrupted on a daily basis for both groups. Measurements and Main Results:The primary outcome was median ventilator days. Secondary outcomes included 28-day ventilator-free survival, intensive care unit and hospital length of stay, and hospital mortality. Median ventilator days were significantly lower in the daily interruption propofol group compared with the intermittent bolus lorazepam group (5.8 vs. 8.4, p = .04). The difference was largest for hospital survivors (4.4 vs. 9.0, p = .006). There was a trend toward greater ventilator-free survival for patients in the daily interruption propofol group (median 18.5 days for propofol vs. 10.2 for lorazepam, p = .06). Hospital mortality was not different. Conclusions:For medical patients requiring >48 hrs of mechanical ventilation, sedation with propofol results in significantly fewer ventilator days compared with intermittent lorazepam when sedatives are interrupted daily.

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/m2) 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.

Continuous intravenous infusions of lorazepam versus midazolam for sedation during mechanical ventilatory support: a prospective, randomized study.

ObjectiveTo evaluate the efficacy of continuous infusions of lorazepam vs. midazolam for sedation in the intensive care unit (ICU).Design:Prospective, randomized study.Setting:Large, urban university hospital.Patients:Twenty adult medical ICU patients receiving mechanical ventilatory support.Interve

Daily sedative interruption in mechanically ventilated patients at risk for coronary artery disease.

Objectives:To determine the prevalence of myocardial ischemia in mechanically ventilated patients with coronary risk factors and compare periods of sedative interruption vs. sedative infusion. Design:Prospective, blinded observational study. Setting:Medical intensive care unit of tertiary care medical center. Patients:Intubated, mechanically ventilated patients with established coronary artery disease risk factors. Interventions:Continuous three-lead Holter monitors with ST-segment analysis by a blinded cardiologist were used to detect myocardial ischemia. Ischemia was defined as ST-segment elevation or depression of >0.1 mV from baseline. Measurements and Main Results:Comparisons between periods of awakening from sedation vs. sedative infusion were made. Vital signs, catecholamine levels, and time with ischemia detected by Holter monitor during the two periods were compared. Heart rate, mean arterial pressure, rate–pressure product, respiratory rate, and catecholamine levels were all significantly higher during sedative interruption. Eighteen of 74 patients (24%) demonstrated ischemic changes. Patients with myocardial ischemia had a longer intensive care unit length of stay (17.4 ± 17.5 vs. 9.6 ± 6.7 days, p = .04). Despite changes in vital signs and catecholamine levels during sedative interruption, fraction of ischemic time did not differ between the time awake vs. time sedated [median [interquartile range] of 0% [0, 0] compared with 0% [0, 0] while they were sedated [p = .17]). The finding of similar fractions of ischemic time between awake and sedated states persisted with analysis of the subgroup of 18 patients with ischemia. Conclusions:Myocardial ischemia is common in critically ill mechanically ventilated patients with coronary artery disease risk factors. Daily sedative interruption is not associated with an increased occurrence of myocardial ischemia in these patients.

Oxygenation in status asthmaticus improves during ventilation with helium-oxygen.

OBJECTIVES To determine the effect of breathing helium-oxygen (HELIOX) mixtures on pulmonary gas exchange during severe asthma. DESIGN A retrospective case-match control design was used to compare the changes in alveolar to arterial gradient [(A-a)gradient] in the first 2 hrs of mechanical ventilation (MV) for status asthmaticus (SA) in patients who received HELIOX with those who did not. Patients were matched for diagnosis of asthma, ventilatory failure, ventilator mode and settings, and equivalent pharmacologic therapy. SETTING The adult and pediatric intensive care units of a tertiary-care hospital. SUBJECTS Adult and pediatric patients undergoing MV for SA. INTERVENTIONS Use of HELIOX or standard nitrogen-oxygen mixtures during MV. MEASUREMENTS AND MAIN RESULTS A total of 11 patients receiving HELIOX in the first 2 hrs of MV for SA were compared with 11 case-matched controls who did not. At baseline, the HELIOX and control groups had similar (A-a)gradients (216+/-92 torr and 226+/-82 torr, respectively). The (A-a)gradient decreased significantly to 85+/-44 torr after initiation of ventilation with HELIOX (p < .0003), whereas it did not change significantly in the control group in a similar time frame and during identical treatment without HELIOX. The reduction in (A-a)gradient in the HELIOX group facilitated a reduction in F(IO)2 from 0.8+/-0.2 initially to 0.4+/-0.1 at the time of the second blood gas determination, thus permitting greater concentrations of helium to be administered. CONCLUSIONS MV with HELIOX improves (A-a)gradient in patients with SA. Although this improvement adds little to routine therapy with supplemental oxygen, it does permit reduction in concentration of inspired oxygen to levels that maximize helium concentration and thus permit full benefits of HELIOX on lung mechanics to be realized in even the most severely ill asthmatics.

Management of the agitated intensive care unit patient

Agitation: 1. Violent motion. 2. Strong or tumultuous emotion. Management of the agitated patient is fast becoming an area of major breakthroughs for critical care medicine. To illustrate, Figure 1 shows the total number of articles found on MEDLINE using a combination of search words related to sedation and critical care. This crude survey demonstrates an exponential rise in activity surrounding this topic and helps support the view that study of agitation in the critically ill patient is of rapidly expanding importance. Moreover, management of the agitated patient has developed into an economically powerful subject, both for pharmaceutical companies and for caregivers interested in improving the efficient use of intensive care unit (ICU) resources. It is increasingly apparent that outcomes are significantly influenced by the manner in which agitation is managed. The quantity of articles being published is only part of the picture. Investigations related to agitation in critical care are yielding a variety of intriguing observations including post-traumatic stress disorder and post-ICU depression, diagnosis of delirium, objective monitoring technology, sleep pattern changes, process/management strategies to enhance clinical and economic outcomes, scoring systems, tailorability of therapeutic approaches, and bronchodilatory, antioxidant, and immunosuppressive properties of sedative agents. Rather than simply discussing strategies for sedation, it is the deliberate intent of this continuing education program to focus on the specific topic of agitation (in the ICU patient). It is noteworthy that, although it is one of the most common issues facing critical care practitioners, agitation in the ICU has no clear and concise definition. The simple definition stated at the beginning of this article is from Funk and Wagnall’s 1982. This explanation of “agitation” has merit because it encompasses both physical and emotional distress. Under this characterization, either the nonsedated paralyzed patient or the comatose patient with patient-ventilator asynchrony can be considered agitated, even though the two may represent opposite ends of a spectrum. Accurate diagnosis of the cause of agitation frequently requires a careful analysis of the patient’s history and physical examination, review of laboratory and other diagnostic data, knowledge of the effectiveness of concomitant therapies, collaboration among members of the team and family, and a good deal of experience. The cause of agitation is often multifactorial (e.g., pain and confusion or delirium and withdrawal), and even with successful management it is difficult to be certain about precipitating factors in any single case. Anecdotes from patients and clinicians can serve as powerful tools for the critical care team’s armamentarium and help increase understanding from both sympathetic and empathetic perspectives. Pharmacologic management strategies for agitation include both prevention and treatment. Prevention commonly guides the hand of the critical care clinician when a patient is being stabilized and drips are ordered for analgesia and sedation in anticipation of agitation. Fine-tuning the therapy using agitation scales, daily awakening, and other strategies take on more of a treatment quality, as do pro re nata (PRN) agitation orders. Nonpharmacological approaches include a variety of environmental adjustments that are frequently underutilized. Yet, as obvious as these concepts for definition, diagnosis, and management may seem, it is difficult to consistently apply them to the literature (with the exception of short-term usage). There are a number of well-designed and wellexecuted studies in longer-duration agitation management but, excluding those in very focused populations (e.g., neurologic injury), most studies lump patients into groups for the purpose of assessing differing sedative regimens. Comparative pharmaceutical trials have been extraordinarily important to clinicians who deal regularly with agitation. These studies, as well as trials using innovative management techniques, are becoming increasingly sophisticated in the area of pharmacoeconomic assessment. There is still, however, a paucity of comprehensive studies evaluating the integration of economic, clinical, and humanistic outcomes of agitated ICU patients. Existing economic analyses include variables such as drug acquisition costs, ventilator duration, and ICU length of stay (LOS) to determine the “cost effectiveness” of one drug regimen over another; these are often only partial in their scope. Assigning or assuming costs for time in ICU or on a ventilator is fraught with the problems of evaluating the fixed and variable components. Opportunity costs are usually ignored, as they are exceedingly difficult to determine. And, failure to include post-ICU cost and outcome information ignores the post-ICU morbidity that appears linked to ICU sedation usage. These types of problems with economic analyses are widespread in the critically ill population and are not unique to the topic of agitation management. Notwithstanding, it can be said with a reasonable degree of confidence that the drug acquisition cost of various regimens is only one—often small—piece of the larger economic puzzle. Given the current tide of activity, it is conceivable that the approach to managing agitation in the critically ill patient will rise (or is rising) to a new level of sophistication. At this new level, pharmacologic and nonpharmacologic approaches will be highly selective and finetuned to more precisely address the Copyright

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.