Critically ill patients frequently

Transcription

1 Clinical trials of early mobilization of critically ill patients John P. Kress, MD Intensive care unit-acquired weakness is a common complication of critical illness leading to severe functional impairment in many intensive care unit survivors. Critically ill patients who require mechanical ventilation are routinely immobilized for prolonged time periods. This immobilization is exacerbated by frequent administration of sedative agents. Recently, several investigators have described the feasibility and potential benefits of mobilizing mechanically ventilated intensive care unit patients. Such an intervention requires a multidisciplinary team approach to patient care, involving nursing, physical therapy, occupational therapy, and respiratory therapy practitioners. Recent studies of early mobilization of mechanically ventilated intensive care unit patients have noted this intervention to be safe and associated with improved functional outcomes in this extremely ill patient cohort. Such outcomes include high percentages of patients able to ambulate on intensive care unit and hospital discharge and shortened hospital length of stay. With preliminary studies demonstrating remarkable feasibility and successes, further prospective studies of early mobilization are needed to evaluate this intervention. (Crit Care Med 2009; 37[Suppl.]:S442 S447) KEY WORDS: mechanical ventilation; clinical protocols; physical therapy; occupational therapy; mobilization; ICU-acquired weakness; critical illness myopathy; muscle atrophy; intensive care unit; neuropathy; sedation Critically ill patients frequently present with an extreme derangement of physiologic homeostasis, leading intensive care unit (ICU) care to focus on recovery from acute organ system failure. Those organ systems whose failure threatens survival (e.g., cardiovascular, pulmonary, renal) accordingly receive greatest attention in the ICU. Patients requiring mechanical ventilation are among the most challenging in this regard. In the midst of ICU care, with its focus on resuscitation and survival, there is customarily little early attention toward neuromuscular function. However, recent work on outcomes in ICU survivors has recognized that these patients suffer profound and persistent impairments in physical function, with recovery that is typically slow and incomplete (1 5). In 109 patients studied 1 yr after recovering from acute respiratory distress syndrome, Herridge and colleagues noted that every patient reported poor function, which was attributed to loss of muscle bulk, proximal From the Department of Medicine, Section of Pulmonary and Critical Care, University of Chicago, Chicago, IL. The author has not disclosed any potential conflicts of interest. For information regarding this article, jkress@medicine.bsd.uchicago.edu Copyright 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: /CCM.0b013e3181b6f9c0 muscle weakness, and fatigue (1). Only half of the patients in this cohort were employed 1 yr after recovery, and the reported reasons for continued unemployment included persistent fatigue, weakness, and poor functional status (e.g., footdrop and large joint immobility). De Jonghe and colleagues described a 25% prevalence of ICU-acquired weakness in a cohort of 95 patients receiving mechanical ventilation (6). The study described independent predictors of ICU-acquired weakness, which included duration of mechanical ventilation, days of multiple system organ failure, corticosteroid administration, and female gender. As clinical recovery from critical illness and respiratory failure describes severe physical deconditioning accompanied by weight loss, profound weakness, and functional impairment (1, 2, 7, 8), a growing body of literature recounts neuropathies and myopathies described categorically as ICU-acquired weakness (9). Although the mechanisms are poorly understood (10), preliminary evidence suggests that muscle injury from systemic inflammation (11, 12), along with deconditioning from immobility (13, 14), may be important. Catabolism with skeletal muscle proteolysis and atrophy are frequently seen in ICU patients and also may contribute to ICU-acquired weakness. To date, there are only limited data suggesting that physical activity may attenuate neuromuscular weakness in critical illness (14). Griffiths et al described the effects of continuous passive motion of one leg in critically ill patients with respiratory failure during neuromuscular blockade, with the contralateral leg serving as a control (14). Muscle fiber atrophy was prevented by this intervention in those with high illness severity. Muscle DNA to protein ratios (an index of wasting) and muscle protein content were reduced less profoundly in the leg receiving continuous passive motion. Other studies described the detriments of prolonged immobility in mechanically ventilated ICU patients (15, 16), and many have speculated on the potential benefits of physical activity in sedentary ICU patients (17 22). Many mechanically ventilated patients receive sedative and analgesic drugs, often in high doses, predisposing them to prolonged periods of unconsciousness and immobility. Previous work has identified excessive ICU sedation as an important cause of prolonged mechanical ventilation and ICU length of study (23 25). Kress et al previously reported that a strategy of daily interruption of sedative infusions in mechanically ventilated ICU patients significantly reduced ventilation time and ICU length of stay (25, 26). Accordingly, strategies that titrate sedative doses downward (24, 27) are used widely for the current management of mechanically ventilated patients. Recently, there has been an interest in physical mobilization of ICU patients requiring mechanical ventilation. Mobiliza- S442

2 Figure 1. Adaptation to the intensive care unit environment (ATICE) instrument. Reprinted with permission from de Jonghe et al (29). tion during mechanical ventilation in the ICU requires patients to be awake and mentally animated (28). Accordingly, sedatives must be minimized and sedation protocols that allow patients to be awake and interactive must be utilized. De Jonghe and colleagues reported the impact of a sedation protocol utilizing the adaptation to the ICU environment instrument (Fig. 1) (29). This algorithm sought to maintain patients in a state where they were comfortable and tolerant yet awake and interactive. The adaptation to the ICU environment instrument has a Consciousness domain (with grades of Awakeness and Comprehension targeted) and a Tolerance domain (with grades of Calmness, Ventilator Synchrony, and Face Relaxation targeted). In a before-after trial comparing usual care with a sedation algorithm utilizing the adaptation to the ICU environment instrument (Fig. 2), the latter resulted in significantly fewer days of mechanical ventilation (4.4 vs days; p.014). Although the trial did not specifically utilize a mobilization protocol, patients subjected to the adaptation to the ICU environment sedation algorithm were noted to have significantly fewer pressure sores (18.6% vs. 37%; p.04). Because pressure sores are directly related to immobility in bed, this study suggests that a more mentally active, minimally sedated patient is more inclined to move around, even while confined to bed. Bailey and colleagues reported the first trial of early mobilization in mechanically ventilated ICU patients (30). In a descriptive prospective cohort study, this group postulated that early mobilization after physiologic stabilization in the ICU might lead to patients accomplishing ambulation by the time of ICU discharge. This study targeted feasibility and safety as end points in a consecutive group of patients with respiratory failure admitted to the respiratory ICU at LDS Hospital in Salt Lake City, UT, over a 7-mo period. Patients mechanically ventilated for 4 days were eligible. Patients admitted to the LDS respiratory ICU were typically transferred from medical and shock trauma ICUs at LDS Hospital. As noted in Table 1, this group had high illness acuity in both the initial ICU and on transfer to the respiratory ICU. Mobilization began when patients demonstrated neurologic stability (i.e., response to verbal stimulation), respiratory stability (i.e., FIO and positive endexpiratory pressure 10 cm H 2 O), and circulatory stability (i.e., absence of orthostatic hypotension and catecholamine infusions), with an assessment for readiness occurring within 24 hrs of admission to the respiratory ICU. The protocol involved participation by a physical and respiratory therapist, nurse, and critical care technician. Three activities were targeted: sitting on the edge of the bed; sitting in a chair after bed transfer; and ambulating. The majority of patients admitted to this respiratory ICU came from other ICUs (94%), and the mean time to admission to this respiratory ICU was days. The investigators studied 103 patients undergoing 1449 activity events, which included 16% bed sitting, 31% chair sitting, and 53% ambulating. A total of 593 of the activity events occurred in intubated patients receiving wide ranges of FIO 2 (Fig. 3). Eighty-three percent of patients survived to hospital discharge with a median ambulation distance of 200 feet. At the end of the respiratory ICU stay, 2.4% of survivors accomplished no activity, 4.7% could sit on the edge of the bed, 15.3% could sit in a chair, 8.2% ambulated 100 feet, and 69.4% ambulated 100 feet. The investigators noted a very low adverse event occurrence rate, despite caring for patients with high illness acuity. One percent of activities had adverse events (five falls to knees without injury, four systolic S443

3 Figure 2. Sedation algorithm utilizing the adaptation to the intensive care unit environment (ATICE) instrument. IV, intravenous; VAS, visual analog score. Table 1. Demographics and selected outcomes Characteristic Mean SD Median Range Age MV duration ICU LOS RICU LOS Hospital LOS Hospital to RICU admission APACHE II scores Initial ICU RICU Multiple organ failure score Initial ICU RICU Highest FIO Lowest PaO 2 /FIO ICU, intensive care unit; LOS, length of stay; RICU, respiratory intensive care unit; APACHE, Acute Physiology and Chronic Health Evaluation; MV, mechanical ventilation. Adapted with permission from Bailey et al (29). blood pressure decreases 90 mm Hg, one systolic blood pressure increase 200 mm Hg, three SpO 2 decreases 80%, and one enteral feeding tube removal). There were no extubations and all adverse events were fully resolved by cessation of activity. This study clearly showed that an unconventional mobilization protocol could be performed in mechanically ventilated patients with success and safety. S444 Thomsen and colleagues expanded on the work by Bailey et al with another study from the LDS respiratory ICU (31). They sought to determine whether immobilization occurred unnecessarily in their other ICUs and was improved on transfer to the respiratory ICU with its focus on aggressive early ambulation. The primary end point of this study was ambulation and each patient served as his/her own control in this beforeafter cohort study. The investigators studied 104 patients. As seen in Figure 4, ambulation increased significantly after transfer to the respiratory ICU from another ICU. By multivariate logistic regression analysis, ambulation was predicted by transfer to the respiratory ICU (odds ratio 2.47; 95% confidence interval ; p.0001), absence of sedatives (odds ratio 1.90; 95% confidence interval ; p.009), female gender (odds ratio 1.88; 95% confidence interval ; p.019) and lower Acute Physiology and Chronic Health Evaluation II score (odds ratio 1.06; 95% confidence interval ; p.017). Eighty-eight percent of patients survived to hospital discharge with a median ambulation distance of 200 feet. This study also confirmed the important relationship between sedation and immobilization. These two studies identified early mobilization as a feasible and safe intervention and set the stage for subsequent comparative interventional studies. It is important to note that the patients in these studies were cared for in another ICU for an average of 10 days before transfer to the respiratory ICU. At the time of these publications, whether even earlier therapy might be feasible and/or beneficial remained unknown.

4 Figure 3. FIO 2 ranges during mobilization. Reprinted with permission from Bailey et al (30). Figure 4. Percentage of patients ambulating before and after transfer to the respiratory intensive care unit (RICU) from another intensive care unit. Reproduced with permission from Thomson et al (31). Morris and colleagues reported the first prospective trial comparing early ICU mobilization with usual care (32). Mechanically ventilated adult patients were enrolled in the trial within 48 hrs of intubation. The assignment to mobilization protocol vs. usual care was done in a nonrandomized manner by block allocation in different ICUs. Patients in both groups were treated with protocols for sepsis resuscitation, glycemic control, daily sedative interruption, and ventilator liberation. The mobilization protocol involved a mobility team (critical care nurse, nursing assistant, physical therapist) using a progressive activity regimen (Fig. 5). The primary outcome of the study was the proportion of patients surviving to hospital discharge who received physical therapy. Secondary outcomes were days until the patient was first out of bed, number of ventilator days, ICU length of stay, and hospital length of stay among survivors. A total of 330 patients were enrolled in the trial (n 165 in each group). There were no adverse events, such as removal of medical devices noted during any of the mobilization sessions. Eighty percent of patients in the mobilization group had at least one physical therapy session compared with 47% in the usual care group (p.001). The mobilization group had fewer days to first out of bed (8.5 vs. 13.7; p.001) and fewer hospital days (14.9 vs. 17.2; p.048). The mobilization protocol in this study occurred only during time in the ICU. Whether ongoing aggressive mobilization after ICU discharge would have offered additional benefit is not known. Another limitation is the lack of blinding, leading to the potential for bias with regard to patient discharge disposition. The reason for shortened hospitalization is not known because the study did not report assessments of strength or functional condition. The authors concluded that further studies assessing these end points were merited. Schweickert and colleagues recently reported findings from a prospective randomized trial of very early physical and occupational therapy from the inception of respiratory failure requiring mechanical ventilation (33). They evaluated medical ICU patients undergoing mechanical ventilation for 72 hrs who were functionally independent before ICU admission. The Barthel Index (34) was used to identify independent functional status, as this tool has demonstrated reliability when assessment is made by proxy (35). Patients randomized to the intervention group underwent a progressive therapy regimen focused on mobilization and achievement of occupational tasks (i.e., activities of daily living). Each morning, patients underwent sedative interruption (25). Once the patient was awake and able to follow commands, a physical and occupational therapist subjected patients to a sequential mobilization protocol. This protocol progressed from range of motion exercises to sitting at the edge of the bed, activities of daily living, transfer training, and ambulation. Progression of the mobilization protocol was dependent on patient tolerance and stability. Patients in the control group underwent physical therapy/occupational therapy as ordered by the primary care team typically occurring after extubation (16, 30, 31, 35 37). All functional outcomes were evaluated by therapists blinded to patient randomization assignment. The primary end point of the trial was the return to functional independence at hospital discharge. This was defined as the ability to perform activities of daily living (bathing, dressing, eating, grooming, transfer from bed to chair, toileting) and walk independently. Intervention patients began therapy at 1.5 days after intubation compared with 7.3 days after intubation in the control group (p.001), with several improved outcomes reported. Independent functional status at hospital discharge occurred in 59% of intervention patients compared with 35% of controls (p.02). The intervention patients were noted to S445

5 Figure 5. Progressive activity regimen. ICU, intensive care unit; OOB, out of bed; ROM, range of motion. Reprinted with permission from Morris et al (32). have greater unassisted ambulatory distance (110 vs. 0 feet; p.004) and more ventilator-free days (23.5 vs. 21.1; p.05). The duration of ICU delirium was shorter in the intervention group (2.0 vs. 4.0 days; p.03) in spite of no differences in sedatives administered. Similar to the other studies (30 32), feasibility of early mobilization was again demonstrated in this trial. With a regimen targeting very early mobilization, many patients achieved activity milestones during mechanical ventilation: sitting at the edge of the bed (78%); standing (51%); transfer to a chair (43%); ambulating 2 steps (25%); and ambulating 100 feet (6%). Major adverse events were uncommon one event in 498 encounters (zero extubations, falls, or systolic blood pressure changes 90 mm Hg or 200 mm Hg; one desaturation 80%) and cessation of therapy as a result of adverse events occurred rarely (4% of all sessions). This study differed from the previous studies in that mobilization occurred extremely early ( 1.5 days after intubation) and measured functional outcomes in a randomized, blinded fashion. CONCLUSIONS Survivors of respiratory failure requiring mechanical ventilation are at high S446 risk for neuromuscular weakness and functional impairment. These problems are often severe and persistent, and for many patients these difficulties may never fully resolve. Given the frequency with which immobilization occurs in these patients while in the ICU, it stands to reason to hypothesize that early mobilization may offer benefit. The area of early ICU mobilization is novel and there is limited evidence at present to guide clinicians. Nevertheless, recent studies have confirmed that mobilization of mechanically ventilated patients is feasible and safe. Furthermore, preliminary evidence suggests that such an intervention may offer improvement in outcomes for these high-risk patients. Further trials to investigate the potential benefits of ICU mobilization are warranted. REFERENCES 1. Herridge MS, Cheung AM, Tansey CM, et al: One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 2003; 348: Cheung AM, Tansey CM, Tomlinson G, et al: Two-year outcomes, health care use, and costs of survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med 2006; 174: Dowdy DW, Eid MP, Dennison CR, et al: Quality of life after acute respiratory distress syndrome: A meta-analysis. Intensive Care Med 2006; 32: Dowdy DW, Eid MP, Sedrakyan A, et al: Quality of life in adult survivors of critical illness: A systematic review of the literature. Intensive Care Med 2005; 31: Herridge MS, Angus DC: Acute lung injury Affecting many lives. N Engl J Med 2005; 353: De Jonghe B, Sharshar T, Lefaucheur JP, et al: Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 2002; 288: Angus DC, Kelley MA, Schmitz RJ, et al: Caring for the critically ill patient. Current and projected workforce requirements for care of the critically ill and patients with pulmonary disease: Can we meet the requirements of an aging population? JAMA 2000; 284: Stevens RD, Dowdy DW, Michaels RK, et al: Neuromuscular dysfunction acquired in critical illness: a systematic review. Intensive Care Med 2007; 33: De Jonghe B, Cook D, Sharshar T, et al: Acquired neuromuscular disorders in critically ill patients: A systematic review. Groupe de Reflexion et d Etude sur les Neuromyopathies En Reanimation. Intensive Care Med 1998; 24: Bogdanski R, Blobner M, Werner C: Critical illness polyneuropathy and myopathy: Do they persist for lifetime? Crit Care Med 2003; 31: Witt NJ, Zochodne DW, Bolton CF, et al: Peripheral nerve function in sepsis and multiple organ failure. Chest 1991; 99: Leijten FS, De Weerd AW, Poortvliet DC, et al: Critical illness polyneuropathy in multiple organ dysfunction syndrome and weaning from the ventilator. Intensive Care Med 1996; 22: Bednarik J, Lukas Z, Vondracek P: Critical illness polyneuromyopathy: The electrophysiological components of a complex entity. Intensive Care Med 2003; 29: Griffiths RD, Palmer TE, Helliwell T, et al: Effect of passive stretching on the wasting of muscle in the critically ill. Nutrition 1995; 11: Bouletreau P, Patricot MC, Saudin F, et al: [Effects of intermittent muscle stimulation on muscle catabolism in patients immobilized in the ICU]. Ann Fr Anesth Reanim 1986; 5: Martin UJ, Hincapie L, Nimchuk M, et al: Impact of whole-body rehabilitation in patients receiving chronic mechanical ventilation. Crit Care Med 2005; 33: Bolton CF, Breuer AC: Critical illness polyneuropathy. Muscle Nerve 1999; 22: Hund E: Neurological complications of sepsis: Critical illness polyneuropathy and myopathy. J Neurol 2001; 248: van der Schaaf M, Beelen A, de Groot IJ: Critical illness polyneuropathy: A summary of the literature on rehabilitation outcome. Disabil Rehabil 2000; 22:

6 20. van Mook WN, Hulsewe-Evers RP: Critical illness polyneuropathy. Curr Opin Crit Care 2002; 8: Morris PE: Moving our critically ill patients: Mobility barriers and benefits. Crit Care Clin 2007; 23: Morris PE, Herridge MS: Early intensive care unit mobility: Future directions. Crit Care Clin 2007; 23: Kollef MH, Levy NT, Ahrens TS, et al: The use of continuous i.v. sedation is associated with prolongation of mechanical ventilation. Chest 1998; 114: Brook AD, Ahrens TS, Schaiff R, et al: Effect of a nursing-implemented sedation protocol on the duration of mechanical ventilation. Crit Care Med 1999; 27: Kress JP, Pohlman AS, O Connor MF, et al: Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000; 342: Girard TD, Kress JP, Fuchs BD, et al: 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. Lancet 2008; 371: De Jonghe B, Bastuji-Garin S, Fangio P, et al: Sedation algorithm in critically ill patients without acute brain injury. Crit Care Med 2005; 33: Petty TL: Suspended life or extending death? Chest 1998; 114: De Jonghe B, Bastuji-Garin S, Fangio P, et al: Sedation algorithm in critically ill patients without acute brain injury. Crit Care Med 2005; 33: Bailey P, Thomsen GE, Spuhler VJ, et al: Early activity is feasible and safe in respiratory failure patients. Crit Care Med 2007; 35: Thomsen GE, Snow GL, Rodriguez L, et al: Patients with respiratory failure increase ambulation after transfer to an intensive care unit where early activity is a priority. Crit Care Med 2008; 36: Morris PE, Goad A, Thompson C, et al: Early intensive care unit mobility therapy in the treatment of acute respiratory failure. Crit Care Med 2008; 36: Schweickert WD, Pohlman MC, Pohlman AS, et al: Early physical and occupational therapy in mechanically ventilated, critically ill patients: A randomised controlled trial. Lancet 2009; 373: Mahoney FI, Barthel DW: Functional evaluation: The Barthel Index. Md State Med J 1965; 14: Collin C, Wade DT, Davies S, et al: The Barthel ADL Index: A reliability study. Int Disabil Stud 1988; 10: Gosselink R, Bott J, Johnson M, et al: Physiotherapy for adult patients with critical illness: Recommendations of the European Respiratory Society and European Society of Intensive Care Medicine Task Force on Physiotherapy for Critically Ill Patients. Intensive Care Med 2008; 34: Hodgin KE, Nordon-Craft A, McFann KK, et al: Physical therapy utilization in intensive care units: Results from a national survey. Crit Care Med 2009; 37: ; quiz S447