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YICCN-2227; No. of Pages 12
ARTICLE IN PRESS
Available online at www.sciencedirect.com
Intensive and Critical Care Nursing (2012) xxx, xxx—xxx
journal homepage: www.elsevier.com/iccn
Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study
Chris Winkelman a,∗, Kimberly D. Johnson b,i, Rana Hejal c,d, Nahida H. Gordon a,k, James Rowbottom e,f, Janis Daly g,h,i, Karen Peereboom b, Alan D. Levine j,l
Case Western Reserve University, Frances Payne Bolton School of Nursing, 10900 Euclid Ave Cleveland, OH 44016, United States The Mobility Study, Case Western Reserve University, Frances Payne Bolton School of Nursing, 10900 Euclid Ave Cleveland, OH 44016, United States c Department of Pulmonary & Critical Care, Case Western Reserve University School of Medicine, 10900 Euclid Ave Cleveland, OH 44016, United States d University Hospitals Case Medical Center, MICU, United States e Departments of Anesthesiology and Surgery, Case Western Reserve University School of Medicine, 10900 Euclid Ave Cleveland, OH 44016, United States f University Hospitals Case Medical Center, SCIU, United States g Department of Neurology, Case Western Reserve University School of Medicine, 10900 Euclid Ave Cleveland, OH 44016, United States h Cognitive and Motor Learning Research Program, LSCDVAMC, United States i Department of Veterans Affairs, United States j School of medicine, Case Western Reserve University, Medical School, 10900 Euclid Ave Cleveland, OH 44016, United States k Department of Bioethics, Case Western Reserve University School of Medicine 10900 Euclid Avenue, Cleveland, OH 44016, United States l Department of Medicine Case Western Reserve University School of Medicine 10900 Euclid Avenue, Cleveland, OH 44106, United States
Accepted 29 February 2012
ICU; Exercise; Intubated;
Summary Background: Determining the optimal timing and progression of mobility exercise has the potential to affect functional recovery of critically ill adults. This study compared standard care with care delivered using a mobility protocol. We examined the effects of exercise on vital signs and inﬂammatory biomarkers and the effects of the nurse-initiated mobility protocol on outcomes.
Corresponding author at: Frances Payne Bolton School of Nursing Case Western Reserve University, 2121 Emergency Drive, Cleveland 44106, OH, USA. Tel.: +1 216 368 0700; fax: +1 216 368 3542. E-mail addresses: email@example.com, Chris.Winkelman@case.edu (C. Winkelman), Kimberly.D.Johnson@case.edu (K.D. Johnson), Rana.Hejal@UHHosptials.org (R. Hejal), Nahida.Gordon@case.edu (N.H. Gordon), James.Rowbottom1@UHHosptials.org (J. Rowbottom), Janis.Daly@case.edu (J. Daly), Karen.Peereboom@case.edu (K. Peereboom), Alan.Levine@case.edu (A.D. Levine). 0964-3397/$ — see front matter © 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.iccn.2012.02.007
Please cite this article in press as: Winkelman C, et al. Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study. Intensive Crit Care Nurs (2012), doi:10.1016/j.iccn.2012.02.007
Patients in both units Please cite this article in press as: Winkelman C. These results should encourage clinicians to add mobility protocols to the care of ICU adults and lead to future studies to determine optimal ‘‘dosing’’ of exercise in ICU patients. no other adverse events occurred. avoiding clinician inertia and long periods of uninterrupted bed rest in intubated adults.007 . We examined the effects of exercise on vital signs and inﬂammatory biomarkers. No. There is limited information about the mechanisms through which progressive mobility exercises contribute to mitigation or prevention of ICU-acquired weakness (Grifﬁths and Hall. 2009). doi:10. 2010. 2010). Pohlman et al. suggesting brief episodes of low intensity exercise positively altered inﬂammatory dysregulation in this sample. of Pages 12 ARTICLE IN PRESS C. Findings suggested the use of a protocol with one 20 minute episode of exercise daily for 2 or more days reduced ICU length of stay.+Model YICCN-2227. Both inﬂammation and immobility have been implicated in intensive care unit (ICU)-acquired weakness and subsequent prolonged functional impairment (Grifﬁths and Hall. 2010). Introduction There are multiple reports of safe implementation of rehabilitative activity among intubated and critically ill patients (Bailey et al. Duration of exercise was linked to increased IL-10. 1)... 2008.. All rights reserved. Results: 75 heterogeneous subjects admitted to a Medical or Surgical intensive care unit (ICU) were enrolled. suggesting that implementing a mobility protocol can improve inﬂammatory dysregulation in patients with prolonged critical illness.2012. The purpose of this study was to compare standard care versus an early mobility protocol in ICU adults. academic medical centre.02. 2009). In <5% of exercise periods. • Less than 5% of exercise periods were associated with a concerning increase in respiratory rate or peripheral oxygen desaturation further adding to the evidence that mobility in intubated and critically ill adults is safe. Schweickert et al. an anti-inﬂammatory cytokine that downregulates the inﬂammatory cascade (Truong et al. Morris et al. and IL-10. Are there associations between change in IL-6 or IL-10 and patient outcomes? 4. Conclusion: A growing body of evidence demonstrates that early. 2007).clinicaltrials. 2007.. progressive mobility is still in progress. repeated measures study with a control period (standard care). 2009.. there was a concerning alteration in respiratory rate or peripheral oxygen saturation. Thomsen et al. • A 20-minute daily period of exercise was linked to an increase in IL-10. an anti-inﬂammatory cytokine. 2 Mechanical ventilation.gov (NCT00787098). The study was registered at www. progressive exercise has signiﬁcant beneﬁts to intubated adults. Stiller et al. urban. However. Is there a difference in patient outcomes for the protocol of mobility therapy compared to standard care? Methods This was a prospective.. Winkelman et al. Zanni et al. 2009. and intervention period with protocol care (see Fig. a proinﬂammatory cytokine that inﬂuences muscle health. repeated measures study with a control (standard care) and intervention (protocol) period.iccn. © 2012 Elsevier Ltd... Is exercise associated with adverse changes in vital signs or unsafe events? 2. Linking mechanisms of inﬂammation to a therapeutic ‘‘dose of mobility exercise’’ can support clinical decisions about starting and progressing mobility exercise. 2004. Winkelman. Inﬂammatory biomarkers Implications for clinical practice • The use of a mobility protocol promoted both earlier initiation and increased progression of exercise. The four speciﬁc research questions were: 1. run-in period. • This report suggests a relatively limited intervention of one 20-minute episode of exercise daily for two or more days initiated by a nurse can demonstrate a signiﬁcant reduction in ICU length of stay. Intensive Crit Care Nurs (2012). 2010. Determining the optimal timing and progression of mobility exercise has the potential to affect functional recovery of critically ill adults who experience prolonged mechanical ventilation (Herridge. We also quantiﬁed the effects of the nurseinitiated mobility exercise protocol according to outcomes. Burtin et al. et al. Setting and sample We recruited patients from December 2007 through March 2009 from the medical and surgical ICUs at a large. Methods: Prospective.. Circulating biomarkers related to both inﬂammation and ICU-acquired weakness include interleukin (IL)-6.1016/j. 2009. Is the mode of exercise or duration of exercise associated with change in IL-6 or IL-10? 3. 2008. Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study. guidelines are not established and establishing best practices for early. This study received approval from the hospital Institutional Review Board and all subjects or their surrogates provided informed consent. Needham and Korupolu.
exercise on Days 1-3. Intensive Crit Care Nurs (2012). Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study. (2) a run-in phase to introduce the protocol to staff members and reﬁne the protocol and (3) a protocol implementation period in which study participants were enrolled. December 2008 || April 2008 (5 pa ents enrolled.. Subjects were assessed for enrolment if they experienced more than 48 hours of mechanical ventilation and were anticipated to continue receiving mechanical ventilation for the next 24 hours. The SpO2 was substituted for PaO2 when PaO2 was not available (Pnadharipande et al. At the time of discharge from the ICU. Physiologic stability was deﬁned using the following parameters: P/F ratio > 100. gender.. delirium was measured using the Confusion Assessment Method for ICU (CAM-ICU) (Ely et al. 2010). During the control phase. Examples of exclusionary conditions included end-stage muscular dystrophy.. Severity of illness was measured using the Acute Physiology and Chronic Health Evaluation (APACHE) 3 Score (Knaus et al.iccn.2012.. 1987) from admission data and the ratio of partial pressure of arterial oxygen (PaO2 ) to fraction of inspired oxygen (FiO2 ) or P/F ratio on the day of exercise. et al. There were three study phases: (1) a control phase in which control subjects were enrolled. length of ICU stay. weight. Occurrence of venous thromboembolism (VTE) was extracted from daily progress notes and reports of related diagnostic tests (e. not included in ﬁnal analyses) || May 2008.1016/j. delirium. Fidelity of treatment was reviewed quarterly by the principal investigator with direct observation. myasthenia gravis.007 . acquired pressure ulcer. and RAs were trained in the reﬁned protocol. diagnosis of a metastatic malignancy. Outcomes were measured during each phase. Vital signs were obtained immediately preceding and during exercise: highest and lowest heart rate. 1972). During the run-in phase. During the intervention period. including bronchial lavage results when documented (Mayhall. dopamine. ﬁve new subjects were enrolled. hip ﬂexion. elbow extension. a consistent research protocol was implemented for 55 new subjects and outcomes were measured.and post.g. comorbid conditions (by number) and daily medications. heart rate 50—125. Please cite this article in press as: Winkelman C. Research assistants (RAs) were not blinded to participant assignment to control or protocol care. The type and duration of exercise was recorded daily.g.+Model YICCN-2227. using criteria established by Norton et al. and the protocol before the study started. end-stage renal disease. systolic blood pressure and SpO2 . On the ﬁrst day of eligibility. No. Identiﬁcation and recruitment of patients were the same during each period. muscle strength. Patient and related measures From the medical record. (2007): ICU admission following a hospital stay of >9 days in the past month. FiO2 < 60% and positive end-expiratory pressure (PEEP) < 10 cm H2 O. mean arterial pressure (MAP) 60—100 mm Hg (SpO2 > 88%. use of data collection forms. Patients with hospice care for high risk of death were also excluded. and no active upward titration of vasoactive (e. 2009). changes in nutrition delivery or changes in sedation.. using the Medical Research Council Scale (0—5. new quadriplegia. with 5 being maximal strength) on four muscle groups: shoulder adduction. knee extension with a maximum score of 40 combining right and left extremity values (Fan et al. with surgical patients receiving co-management by surgeons... Outcomes of duration of mechanical ventilation. the Charlson Comorbidity Index (Charlson et al. patient data were abstracted for age. 2001). muscular or orthopaedic disorders that precluded the possibility of progressive mobility. venothromboembolism occurrence. increased intracranial pressure. discharge loca on a er ICU).March 2009 Figure 1 Experimental design and timeline. 1970) with either patient or proxy interview. Muscle strength was measured manually at discharge from the ICU. standard care was observed and recorded for 20 subjects.g.. unrepaired hip fracture and multiple lower extremity fractures. are managed by intensivists. respiratory rate. days of mechanical ven la on. length of ICU stay and discharge location (including mortality) were abstracted from records within 24 hours of ICU discharge. age >80 in the presence of two or more life-threatening illnesses (e. function was measured using the Katz Activities of Daily Living scale (Katz et al. Unsafe events were recorded at the time of occurrence and monitored for potential occurrence in the 15 minutes following exercise. duplex sonography of lower extremities. Patients were asked to separately rate fatigue and pain after an exercise session using a scale of 0 (no fatigue or pain) to 10 (worst possible fatigue or pain). Procedure There were three phases of the study. the patient was evaluated for physiologic stability before beginning the consent process.. of Pages 12 ARTICLE IN PRESS 3 Examining the positive effects of exercise in intubated adults Control || Protocol introduc on and reﬁnement || Protocol implementa on Variables measured in all periods: biomarkers pre. the intervention was reﬁned for feasibility within the speciﬁc environment. 1991). and diagnosis of intracerebral haemorrhage requiring mechanical ventilation.02. Data collectors were trained in medical record data abstraction. unexplained coma. height. although the subjects enrolled during the run-in period were not included in analysis as the number of subjects is small and they received a combined control and protocol-directed delivery of exercise. dobutamine. At ICU discharge. 7 and 14. 2001). Diagnosis of ventilator associated pneumonia (VAP) was determined by research staff using established criteria (Johanson et al. Subjects were excluded from the study if they had neurological. status post cardiac arrest with coma. admitting diagnosis. Field notes were used to record changes in practice such as new equipment use. computerised tomography of the chest and ventilation-perfusion scan). severe heart failure). Data collectors were evaluated and achieved an inter-rater reliability of more than 95% at baseline and every six months for chart abstraction. ven lator-associated pneumonia. doi:10.
13% potential exercise sessions did not occur). Patients were monitored for a 30—60 minute period of rest. In a few participants. 2008): ability to follow three out of ﬁve directions. with established reliability and validity. there were 152 opportunities for daily exercise. 2012). presence/absence of delirium and ventilator-associated pneumonia). 2) and their characteristics are summarised in Table 1. 2012). Throughout all exercise sessions. 4 neosynepherine. RAs trained to implement the protocol in a standard manner. Patients in the experimental group received their ﬁrst exercise intervention on the day of enrolment. the most common reason for not implementing daily exercise was ‘‘change in status or procedure’’ (e. 2007.iccn.. 55 subjects received 20 minutes of exercise once daily for 2—7 days. waiting until evening family visits or allowing family members time to think about the decision to enrol) necessitated starting the ﬁrst exercise 12—24 hours after the patient met inclusion criteria. propofol)) intravenous drugs in the previous four hours.g. Winkelman et al. of Pages 12 ARTICLE IN PRESS C.007 . a common approach to mobility exercise was not in place in either unit. Serum was analysed in the Clinical Research Unit using a Meso Scale Discovery technology. new/upward titration of vasopressor. vital signs were continuously monitored. the time needed to acquire informed consent (e. There were contrasting reasons regarding why ‘‘no exercise’’ occurred on a given day for each of the two groups. and 143 of these exercises were completed (i. The ﬁrst three research questions were tested using a mixed model. Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study... doi:10. There were significantly more women and a signiﬁcantly higher ICU admission acuity (APACHE 3 score) among patients enrolled during the intervention period. Daily awakening/sedation holidays were not common practice during the data collection period (2009) although nonsedated participants did receive a spontaneous breathing trial daily per MICU and SICU practice. Findings Sample A total of 75 patients form the sample (Fig. In comparison.+Model YICCN-2227. we did not pursue consent. for the 55 patients who received the experimental intervention for three days after enrolment. 2012). However. During the intervention period. While resting data could be collected preor post-exercise. When instability persisted beyond 14 days. Chi square tests were used to examine differences in categorical outcomes (e. The most common reason for waiting for enrolment/exercise until day 6 was physiologic instability. If a patient was unstable on the ﬁrst eligible day of enrolment. lift both arms off the bed and/or lift each leg off the bed. customdesigned to simultaneously test both interleukins with an antibody luminescence signal (Mesoscale. If no exercise was planned. and analysis of variance (ANOVA) was used to evaluate differences in muscle strength between groups (SAS Analytics Pro.e. then data were collected around a period of turning or repositioning. No changes in practice during the course of the study occurred in managing continuous sedation. Patients in the control group received their ﬁrst activity on average at day 9 after ICU admission. 2008). VTE prophylaxis or weaning trials during the period of enrolment. nor did participants routinely receive exercise from a physical therapist. demographic and resting data were collected. see Morris et al. midazolam. the P/F ratios for participants on enrolment day were similar in the control and intervention periods (225 versus 220. Continuous variables were examined with ttests (i. Vollman. allowing greater ease in bringing patients to the standing position.. However..g. epinephrine) or sedative (e. During the period of standard care.. 6% potential exercise sessions did not occur). one would not expect differing results from resting values as long as the values reﬂect a period of no exercise or other inﬂammatory intervention. No.. For the patients receiving standard care. About 20% of enrollees in both control and intervention periods received continuous sedation during their participation in the study. reasoning that ‘‘early’’ progressive mobility was not feasible. et al.g. Mobility exercises For the 20 patients who received standard care. Research assistants initiated all in-bed exercise and either assisted with or initiated out-of-bed exercise based on the protocol’s criteria (Morris et al. Intensive Crit Care Nurs (2012). SAS. repeated-measures multivariate analysis of variance. it would always occur after a period of observed rest. there were 46 potential episodes of once daily exercise over the three days subsequent to enrolment and 40 episodes were completed (i. In the run-in phase of the study.. Data from the ﬁve participants enrolled during the run-in period were not included in analysis as these participants received neither standard nor protocolised care. subsequently published.. about 30% of ICU beds were replaced during the study period. n = 5).e.2012. respectively). and then either monitored during a period of exercise planned by the bedside nurse (control) or engaged in 20 minutes exercise by a RA using a protocol developed by Peter Morris (personal communication January. research assistants observed an exercise period initiated by the bedside nurse. we followed his/her status daily until stability was achieved. Following consent. Controls were included with each plate conﬁrming detection limits and all patient samples were run in duplicate. continuous variables of duration of mechanical Please cite this article in press as: Winkelman C. the most common reason for no exercise was ‘‘no activity planned’’ as reported by the bedside nurse.1016/j. As cytokines and vital signs (VS) typically return to baseline well within the minimal observed time of 30 minutes at rest (Winkelman et al.e. Participants were followed until discharge from the ICU.. In the standard care (control) phase. newly unstable vital signs. A second reason was patient request/decline of intervention (n = 4). ventilation and length of stay in the ICU). For patients who received the experimental intervention. tracheostomy procedure. the most common reason voiced by staff nurses for starting activity Statistical analysis Data related to the sample are presented with descriptive statistics. The new bed frames were closer to the ﬂoor.02.g. 2007. Biomarkers were collected from serum samples for three consecutive days after enrolment and again at day 7 after enrolment.
Intensive Crit Care Nurs (2012). without titration during exercise in the intervention group and no clinically important changes in vital signs occurred despite vasopressor support. screened for inclusion criteria n = 338 Did not qualify due to: 38 • Acute neurologic or chronic neuromuscular deﬁcits (unable to par cipate in exercise progression) n = 113 Persistent hemodynamic instability (> 10-14 days) n = 80 Pre-hospital dysfunc on (e. specifically. respiratpry rate (RR) and sutolic blood pressure (SBP) and the lowest values of peripheral saturation (SpO2 ) during exercise are summarised in Table 3. Table 2 summarises activities during days 1—3 after enrolment. For the intervention group.2012. 20% change in VS).. of Pages 12 ARTICLE IN PRESS 5 N = 835 pa ents received mechanical ven la on (MV) on screening days SICU = 381 poten al par cipants MICU = 454 poten al par cipants Examining the positive effects of exercise in intubated adults n = 389 < 48 hours MV n = 446 with > 48 hours MV. pa ent unable to give informed consent n = 13 n = 108 Consent Discussion Declined n = 28 Consent obtained n = 80 Run-in period Received a mix of control and protocol care n=5 Control n = 20 Interven on n = 55 • • • • • • Figure 2 Screened and enrolled participant ﬂow diagram. No. Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study. While patients were followed weekly after enrolment.. Concerning changes in vital signs occurred six times as an increased respiratory rate >35 breaths per minute and reduced SpO2 to 90% during exercise. exercise was slowed or stopped.iccn. stopping the exercise resulted in a return to resting values within 3—5 minutes. pa ent bedfast or unable to complete 3 out of 5 ac vi es of daily living independently) n = 44 Over weight limit for safe mobiliza on (> 155 kg) n = 32 End-of-life care planned/implemented n = 32 Planned extuba on within 12 hours of qualifying enrollment me. Overall. Post-exercise.02. when changes in vital signs occurred that caused concern (i. There were no periods of hypotension or hypertension requiring cessation of exercise.g. Two patients were on low dose norepinephrine Please cite this article in press as: Winkelman C. the inadvertent removal of an arterial line. was ‘‘the patient is ready now’’ citing vital stability over 24—48 hours as the trigger for readiness. et al.e. These concerning changes all occurred while preparing the patient for a standing transfer to the chair for the ﬁrst time. there were no signiﬁcant increases in pain or fatigue reported by the patients who were able to use a numeric scale to indicate these symptoms as shown in Table 4. the number of participants receiving the experimental intervention on days 4—7 dropped 80% due to discharge from ICU.1016/j. Adverse events One adverse event occurred in the control group. with a higher percentage of the experimental intervention group versus the control group experiencing chair-sitting or standing during the intervention period (25% or 14 enrollees in the intervention group versus 10% or two enrollees in the control group). ac vely/ successfully weaning n = 24 Unable to ini ate consent discussion due to unavailable proxy.007 . 16/75 (21%) subjects experienced out-of-bed exercise within 3 days of enrolment.+Model YICCN-2227. limiting additional comparisons across those latter days. There were no occurrences of new dysrhythmias concurrent with or Vital signs The average differences between resting values and the highest values of heart rate (HR). doi:10. The most common mode of exercise in both groups was inbed active and passive range of motion.
2012.49) 226 (81. SICU = surgical intensive care unit. p < .9) 15% 13% 9% 2% 3 (1.27) 53% 58% 40% (2% Hispanic) 31.5) 11% Abbreviations: SD = standard deviation.2 (.31) 223 (110. PU number of days of mechanical ventilation. mean kg/m2 (SD) Admitting unit MICU SICU Admitting diagnosis (category) Respiratory failure/acute lung injury Cardiovascular surgery Cardiovascular medicine (endocarditis) Gastrointestinal medicine or surgery (e.0 (6. breast and colon) Sepsis Other: acute renal failure and esophagotracheal ﬁstula) Number of comorbid conditions by mean number of categories (SD)/Charlson Score (SD) APACHE* 3 score on admission. Control. mean (SD) Receiving continuous sedation on enrolment All subjects.21) 49% 51% 31% 21% 2% 21% 5% 5% 5% 2 (1.46)/1.02.67)/2. mean (SD) Gender* : Male Race White African American Body mass index. 3 and 7 after enrolment. n = 20 66 (11. Outcomes Outcomes are summarised in Table 6 for delirium. VTE. duplicates varied <. Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study.8) 9% 12% 3% 3% 3 (1. and then averaged. APACHE 3 = acute physiology and chronic health evaluation. MICU = medical intensive care unit.93) 58 (18. 2.96) 222 (119. perforated bowel repair.93) 55% 45% 34% 11% 5% 22% Demographics Age in years.99) 35% 65% 20% 40% 0% 25% Intervention.98. of Pages 12 ARTICLE IN PRESS C. small bowel obstruction repair) Cancer (i. Intensive Crit Care Nurs (2012).15). * Signiﬁcant differences between groups. number of exercise sessions Episodes of chair sitting Episodes of standing or walking ROM = range of motion. et al. n = 55 65 (13. number of exercise sessions (one/day/patient. There were no falls or near-falls during exercise at any time.64)/2. n = 75 666 (12.. a Patients who stood or walked all had a chair-sitting period. VAP. repeated values of exercise value minus resting values for days 1. Inﬂammatory biomarkers Table 5 provides the values of IL-6 and IL-10 at rest and after exercise on days 1. thyroid. Winkelman et al. p = .e.1 ng/mL. The mean change values (i. 2.03) 40% 60% 40% 315 (7. Each sample was run in duplicate to verify results.+Model YICCN-2227.84) 70 (22. version 3. not all patients were in ICU for 72 hours) Episodes of passive ROM Episodes of combined active/passive ROM or Active ROM Out-of-bed. upper GI bleed.4 (1. mean (SD) P/F ratio on admission. Control Mean 17 (range 5—25) 9 37 7 30 5 4(2 patients) 1(1 patient)a Intervention Mean 20 (range 12—60) 6 123 23 100 40 32(14 patients) 8(7 patients)a Duration in minutes Day of ﬁrst exercise session after ICU admission In-bed.iccn. adrenal.99) 75 (21.1 (1. Table 2 Descriptive summary of mobility exercise. No.g.05. immediately following exercise.1016/j.. 3 and 7 after enrolment) were used in analyses for the research questions.e.68) 51% 60% 39% 31 (7. P/F ratio = the partial pressure of arterial oxygen (PaO2 )/the fraction of inspired oxygen (FiO2 ).007 . Biomarkers had similar values during usual care compared to protocolised care (F = 1. doi:10. 6 Table 1 Patient characteristics. length of ICU Please cite this article in press as: Winkelman C. pancreatitis. The mean change was calculated for each patient.
4 3. On average.and post-scores in either pain or fatigue on days 1—3 in those who were able to report. a Day refers to day of enrolment: generally ICU day 3—16. comparing preexercise and post-exercise self-reports in patients who were able to self-report using a scale of 0—10 (zero = none. there were no clinically important changes in vital signs.+Model YICCN-2227. HR increased 6—7 beats/minute.. above). et al.7 2. race. RR.9 by the study monitoring committee members deemed deaths were not associated with the intervention. gender. 5 patients (7%) died while in the ICU.10.6 2. review Associations between biomarkers and exercise There were no signiﬁcant associations between patient characteristics (age. Day 1 n = 19 Pre-exercise fatigue Post-exercise fatigue Pre-exercise pain Post exercise pain 5.1016/j.4 2. Associations between vital signs and exercise There were no signiﬁcant differences in the changes for HR. Day 1a n = 70 98 100 31 33 (135) (139) (136) (154) Day 2a n = 48 70 (73) 73 (74) 50 (261) 55 (304) Day 3a n = 30 83 (110) 83 (39) 74 (337) 75 (347) Day 7a n = 11 107 139) 113 (140) 17 (19) 17 (19) Cytokines (ng/mL) Mean (SD) IL-6 rest IL-6 after exercise IL-10 rest IL-10 after exercise Abbreviations: ng = nanogram.8 Day 2 N = 20 4. Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study. Table 5 Inﬂammatory biomarkers: interleukin (IL)-6 and IL-10. Intensive Crit Care Nurs (2012).2012.10). stay and discharge location after ICU. SD = standard deviation. Heart rate Mean change (SD) Respiratory rate Mean change (SD) Systolic blood pressure Mean change (SD) Peripheral oxygenation (SpO2 ) Mean change (SD) 2(2) 2(2) 2(1) 2(2) 2(2) 2(2) 2(2) 2(3) 2(3) 2(1) 2(1) 2(1) Day 1 Control Intervention Total Day 2 Control Intervention Total Day 3 Control Intervention Total Day 7 Control Intervention Total 7(5) 6(5) 6(5) 7(5) 6(5) 6(5) 7(5) 6(4) 6(5) 9(6) 7(6) 8(6) 6(4) 5(4) 5(4) 6(5) 5(4) 5(4) 6(5) 5(4) 5(4) 5(4) 5(4) 5(4) 15(13) 13(13) 13(13) 15(12) 14(13) 14(12) 15(8) 14(13) 14(12) 16(11) 16(20) 16(18) Abbreviations: SD = standard deviation.3 2. p > .0 Day 3 N = 14 5. Table 4 Changes in pain and fatigue. with the exception of 6 occurrences which concerned alterations in respiratory-related values that led to slowing/ceasing exercise (see adverse events.8 5. >14 hours) after exercise.02.91 4. RR increased 5—6 breaths/minute. During exercise. values not shown. APACHE 3 score and number of comorbidities) and IL-6. body mass index [BMI]. SBP or SpO2 between periods of rest or exercise (ANOVA. SBP increased 13—16 mm Hg and SpO2 typically decreased 2 (e. Please cite this article in press as: Winkelman C. doi:10. these participants were in the intervention group.g. 10 = worst/greatest possible).g. p > . Measures of muscle strength and function are also summarised. All deaths occurred many hours (e. Of the 75 enrolled subjects.9 2. 96—94%).iccn.007 . No signiﬁcant differences in resting values compared to intervention values.6 5. No.. mL = millilitre. of Pages 12 ARTICLE IN PRESS 7 Examining the positive effects of exercise in intubated adults Table 3 Changes in vital signs during mobility exercise. No signiﬁcant differences between pre.
race. it conﬁrms that exercise in relatively stable.13). p = .2012. Control n = 20 Muscle strength Function (Katz total score) Delirium (number of occurrences) Ventilator associated pneumonia (number of occurrences) Venothromboembolism event (number of occurrences) Pressure ulcer (number of occurrences) Duration of mechanical ventilation in days Length of stay in the ICU in days Discharge location Mortality Acute care. Signiﬁcant differences occurred in the ICU length of stay. Discussion This study extends the literature regarding early. 8 Table 6 Comparing outcomes between study periods. group. Associations between control and intervention periods of exercise and outcomes Outcome variables are summarised in Table 6. APACHE 3 score and number of comorbidities (Table 7). VTE.7) or duration of exercise (p = .7) 0 12 8 0 = 1. VAP. First. group (control versus intervention).+Model YICCN-2227.17.327) = 1.9) after controlling for resting IL-6.5 (SD = 7.16 to .43.352 (p = 0. No. group (control versus intervention).133) = 1.146 (p = . duration of mechanical ventilation and ICU LOS (p = . age. p = .03).13 (SD = 6. of Pages 12 ARTICLE IN PRESS C. the lower the IL-10 in participants both during control and intervention periods (F = 7.299 (p = 0. APACHE 3 score and number of comorbidities. Second.9) 19.6) 14. age.6 (SD = 10.9). gender. p = .7) after controlling for resting IL-6.1 (SD = 9. p = . VAP. there were no signiﬁcant associations between change in IL-6 and either mode (p = .07) = Chi square.03. positive relationship between resting IL10 and the patient characteristic of age (F = 2. it Please cite this article in press as: Winkelman C. In separate mixed model analysis. body mass index. VTE and pressure ulcers and no differences between patients enrolled during the control and intervention periods for these four outcomes (p > . et al. Changes in IL-6 and IL-10 were used to examine associations with mode (in-bed versus out-of-bed) and duration (time in minutes) of exercise.4 (SD = 8. Associations between biomarkers and outcomes Using a third mixed model analysis.02.5) 16.07) t = 2.458 (p = .643) 2 26/40 n = 15 1. VAP.2/6 n = 44 9 n = 48 0 11 5 9. There were no signiﬁcant associations between fatigue or pain and resting IL-10 (p = 1). The duration of mechanical ventilation was not different between groups (p = . gender.835 (p = .iccn. Intensive Crit Care Nurs (2012).007 . VTE.258 (p = 0.262) = 3. the change in IL-10 was not associated with outcomes of delirium. doi:10. There were few occurrences of delirium.8).8) after controlling for resting IL-10.155 (p = . intubated adults in the ICU is safe.4/40 n = 49 2.7) 5 41 7 2 All subjects N = 75 25.187) 2 2 2 2 t = 1. progressive mobility for intubated patients in the ICU with three major ﬁndings. BMI. there was no association between the change in IL-6 and outcome measures of delirium. race. Participants enrolled in the intervention period experienced 5 fewer days of ICU hospitalisation despite higher acuity on admission to the ICU compared to the control group. SD = standard deviation. gender. skilled nursing facility Home Abbreviations: 2 Intervention n = 55 22. age. rehabilitation Long-term care.07).02) but not pain (F = 0. duration of mechanical ventilation and ICU length of stay (LOS) (p = . APACHE 3 score and total number of comorbidities. t = t-test. Differences in discharge location did not demonstrate statistical signiﬁcance (p = .52) = 2/259 (p = 0.6) 5 54 15 2 Difference F = .78.1016/j.6 (SD = 8.07). Using a mixed model of repeated measures of multivariate analysis of variance. There was a single.01.7 n = 17 7 n = 14 1 2 4 12. there was a statistically signiﬁcant association between change in IL-10 and duration of exercise: the greater the duration of exercise. Using the same controlling factors for the IL-10 model.8/40 n = 64 2. acquired PU. race.16 to . Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study.01). Mode of exercise was not associated with changes in IL-10 (p = . BMI. Change in IL-6 was marginally associated with discharge location (F = 4.07). acquired PU.250 (p = . p = .0/6 n = 61 16 n = 63 1 13 9 10. Winkelman et al. Change in IL-6 was associated with self-reported fatigue (F = 6.03) 2 = 7.
1016/j. exercise and outcomes. Instead. it may be that serum IL-6 is a less speciﬁc predictor than expression of IL-6 in activated white blood cells. once-daily exercise was not statistically associated with adverse changes in vital signs or unsafe events. No. The high values and great variation appear congruent with inﬂammatory dysregulation common to ICU patients (Chien et al.iccn. These ﬁndings are consistent with research reports on similar populations (Bailey et al. pre-hospital muscle strength was unknown in this sample.. No study has reported prolonged adverse sequelae from respiratory changes. 2009. venousthromboembolism.2 for intubated patients before initiating exercise (Bailey et al. Further. Pro-inﬂammatory biomarkers have been linked to both impaired muscle contractility and muscle atrophy (Brandt and Pedersen. A strategy to reduce respiratory-related derangements during exercise suggested by one research group is to increase FiO2 by . mitigating muscle dysfunction.59 .. Morris et al.2012.. 2008). While neither inﬂammatory cascade molecule was associated with muscle strength at discharge from ICU. Morris et al.27 . the current results showed that high levels of serum IL-6 were not associated with mortality (Dimopoulou et al.87 . this seems a practical approach to use in patients with low respiratory reserve. 2010).03 . doi:10. F value ..25 . of Pages 12 ARTICLE IN PRESS 9 Examining the positive effects of exercise in intubated adults Table 7 Variables IL-6 Change Change Change Change Change Change Change IL-10 Change Change Change Change Change Change Change in in in in in in in in in in in in in in IL-6 IL-6 IL-6 IL-6 IL-6 IL-6 IL-6 and and and and and and and mode of exercise duration of exercise muscle strength function duration of mechanical ventilation ICU length of stay discharge location or mortality mode of exercise duration of exercise* muscle strength function duration of mechanical ventilation ICU length of stay discharge location or mortality Results from examining associations between biomarkers. <7%.27 . It may be that exercise increased musclederived IL-6 not detected in serum samples. Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study. IL-6 is associated with stimulation of IL-10 synthesis. In this study.83 . 2009). * Signiﬁcant interaction at p < . 21% of participants were unable to participate in manual muscle testing (see Table 6). As in our study. 20 minutes of low level exercise was associated with increase IL-10.70 .82 1.. Further studies are needed to evaluate IL-6 and IL-10 effects on muscle strength and function during acute and chronic critical illness.05 7. Longitudinal methodology and multimodal measures Please cite this article in press as: Winkelman C. The most likely explanation for greater mortality of participants enrolled during the intervention period is their greater illness severity (Table 2). 2009.. the use of a protocol promoted early and progressive exercise was associated with decreased length of stay.+Model YICCN-2227. participants demonstrated abnormally increased resting values for both pro. While we did not increase FiO2 in our protocol.45 . Both inﬂammation and immobility have been identiﬁed as independent contributors to muscle weakness (Chambers et al.007 . stimulating increased IL-10... Rehabilitation in other ICU populations has been associated with improved patient outcomes of muscle strength and overall function (Burtin et al.78 1.. an anti-inﬂammatory biomarker. 2006).47 .08 Degrees of freedom 16 121 31 31 65 69 31 16 121 31 31 65 69 31 p (signiﬁcance) . 2010). It may be that exercise reduces the inﬂammatory milieu in ICU patients. In the current study.49 .e.15 0 . 2010. In this study. Pohlman et al. Jastrow et al..and antiinﬂammatory biomarkers compared to values of healthy individuals. The inability to measure muscle strength in a signiﬁcant proportion of the sample limits the ability to draw conclusions from these results. due to cognitive impairment. 2009. Pohlman et al...13 . 2008). 2004. Intensive Crit Care Nurs (2012). Third.46 .79 IL-10 IL-10 IL-10 IL-10 IL-10 IL-10 IL-10 and and and and and and and Note: Too few instances of delirium. Unlike previous reports in the literature.. insufﬁcient power to detect differences). 2009.57 1..02. Thomsen et al.67 ...56 .05 illustrates that exercise does not appear to contribute to a pro-inﬂammatory milieu in serum. Thomsen et al. 2008. This ﬁnding is likely due to the few number of deaths in this study (i. the duration of exercise was associated with a statistically signiﬁcant increase in the anti-inﬂammatory biomarker IL-10 and no increase in IL-6. 2008.95 . 2011).. 2007. Truong et al. Lee et al. Schweickert et al. 2010).37 .03 . 2010. 2011). Testing muscle strength is a challenge reported by other investigation ICU-acquired weakness (Grifﬁths and Hall.61 . ventilator-associated pneumonia and new pressure ulcer formation for analysis. et al. 2010.01 . Alternatively. Abbreviations: IL = interleukin. 2007. Low mortality is attributed to selection criteria of physiologic stability for enrolment. Pedersen. clinically important detrimental changes in respiratory status have been reported during <10% of exercise episodes (Stiller et al.. Needham and Korupolu.
The protocol was consistently applied (ﬁdelity maintained at >90%) and this indicates a potential clinical utility in that it was able to be used consistently with minimal training and no re-training required. This study provided an interrupted series of exercise (no exercise on Saturdays and Sundays) and we did not record additional Please cite this article in press as: Winkelman C.02. 2009. doi:10. Several mobility protocols recommend a 3—5 member team to implement exercise. 2007. While not all patients were able to be tested for delirium due to inability to assess (i. of Pages 12 ARTICLE IN PRESS C. Progression of exercise requires that critically ill patients are alert and able to engage in activities (Kasotakis et al. For example. a Richmond Agitation Sedation Scale [RASS] score of −3 or −4).. any exercise (standard or protocolised) provides an opportunity for patients to have verbal interaction with a staff member. The protocol was initiated by a RA. 2010a.. with membership including the RN research assistant and available unit personnel.007 . the ﬁnding of low incidence of delirium indirectly suggests that mobility exercises or the combination of exercise and limited sedation may contribute to reduced delirium. Others have written about the inﬂuence of ICU culture on initiating and progressing exercise for intubated adults (Hopkins et al. It may be that the use of a RA (i. such as allowing patients or staff to decline participation.. Winkelman et al. Nonetheless. in this protocol. Based on one report. At the time of the study. following directions or hearing conversational cues about sensation and movement) are beneﬁcial to preserving cognitive function during prolonged critical illness and recovery. et al. The ﬁrst exercise session occurred on day 6 for the intervention group versus day 9 for the control group. Kasotakis et al. Perme and Chandrashekar. Our inclusion criteria for physiological stability may be overly cautious. No..iccn. increased duration of exercise. 2005). Fewer participants exhibited delirium at discharge from the ICU than anticipated from recent reports (Vasilevskis et al. Thomsen et al. both surgical and medical patients were included and the heterogeneity of the sample is similar to generic ICU populations in the United States. Alternatively.. Our protocol provided a focused exam to determine patient readiness and the mode of exercise (in-bed or out-of-bed). Teamwork can reduce missed nursing care (Kalisch and Lee. 2010). There were few complications typically associated with prolonged bed rest such as VTE or PU. In this current nurse-initiated protocol. Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study. However. 2010). There may have been ascertainment bias in identifying VTE as this complication may be undiagnosed but present in asymptomatic patients. 2010.b). 2010. using a broader definition of physiological stability to implement the protocol within 48 hours of admission may result in further improvements in outcomes (Fan. but these ﬁndings may be attributed to VTE and pressure ulcer prevention protocols that were well-established in the setting.. Winkelman et al. While the numbers of participants in the control or experimental arms of the study varied (20 versus 55).e. so we are unable to comment on the progression or resolution of delirium as a result of daily exercise.. Some surrogates served as cheerleaders during a session and asked for instructions about exercise strategies to use after ICU discharge. 2006.. not a regular staff member of the ICUs. Other reports of progressive mobility for intubated adults reported ﬁrst out of bed activity on days 7—10 after ICU admission (Bailey et al.. all ‘‘teams’’ were ad hoc. One setting uses a mobility team dedicated to assessing and implementing exercise. 2010. Providing mobility exercise is time-consuming and labour intensive (Winkelman et al. and more episodes of out-of-bed exercise. ICU RNs not employed in the setting) to initiate progressive mobility had unintended consequences. both amount and duration of mobility exercise increased. 2007). One serendipitous ﬁnding was the high level of acceptance by patients and their surrogates in this study. progressive mobility (Hopkins and Spuhler. Assessing patient readiness and response to mobility exercise is challenging. Several other studies report the value of a physical therapist to initiate and progress exercise. Turning and mobility are reported as one of the most commonly missed nursing interventions (Kalisch. 2009. despite greater admission acuity among intervention participants (see Table 2). The consent rate was high (74%) and consistent through 14 months of data collection. Limitations This was a single site study. the use of a protocol promoted early and progressive exercise compared to standard care. 2008. Very few participants in either group received continuous sedation at the time of enrolment in this study. While a few participants declined one exercise session.. 2011). 2010). In this study. physiological parameters were monitored to maintain a relatively stable status. 2007.1016/j. including a registered nurse (RN). Morris and Herridge. Pohlman et al. ICU staff identiﬁed potential patients for enrolment and actively contributed to exercise regimens. an occupational therapist and aide or nonprofessional assistant (Morris et al. 2008). 2011) improves quality indicators in a variety of institutions. 2009)..+Model YICCN-2227. the statistical methods used for analysis are robust to unequal group comparisons. The protocol used herein was clinically useful as evidenced by a number of results from the intervention group: reduced number of missed opportunities for exercise.. a physical therapist. there is increasing evidence that the use of protocols for mobility (Hildreth et al. 2009.g. Improved progression to out-of-bed activity has been reported when a dedicated staff initiates exercise in intubated adults (Kasotakis et al. a respiratory therapist.2012.. and it may be that the psychosocial aspects of mobility (e.. typically a RN and nursing assistant. patients could decline participation as well as individual sessions of exercise. delirium was not assessed daily as part of ICU practice. Use of a ‘‘clinical outsider’’ may not be an ideal strategy to facilitate early. Needham and Korupolu.. Intensive Crit Care Nurs (2012).. Research staff anecdotally reported feeling welcomed in the ICUs. 2010.e. 2010a. There were no differences in the number of patients with delirium in each group. While the impact of the initiating personnel is not clear regarding the inﬂuence on the success of mobility therapy.. despite limited resources. Because this was a research project. Patients enrolled in the mobility protocol had significantly fewer ICU days.. 10 of muscle strength may be able to better evaluate linkages between inﬂammatory biomarkers and muscle function. Perme and Chandrashekar. Schweickert et al. 2005). Vasilevskis et al. Needham and Korupolu. Pohlman et al.b). most patients were eager to engage in exercise at each opportunity. 2011.
Yu CJ. What is stopping us from early mobility in the intensive care unit? Critical Care Medicine 2010. Hseuh PR.iccn. RH and JR participated in study design.1016/j. Journal of Chronic Diseases 1987.2012. Plasma pro. Ciesla ND. grant B5080S. We are grateful for her contributions and wish her well in her career in Taiwan. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. Mitten-Long D. contributed to original and edited sections in the multiple manuscript revisions. Herridge MS. Critical Care Medicine 2009. Dimopoulou I.38(11):2254—5. American Surgeon 2010. initiated study planning and participated in all aspects of study implementation. Physical inactivity and muscle weakness in the critically ill. Clerckx B. Early activity is feasible and safe in respiratory failure patients. Fasaway J. Conﬂict of interests The authors state they have no competing interests related to this manuscript. Fan E. contributed to the implementation of the patient activities promoted in this study. MacKenzie CR. et al. Francis J. implementation. Intensive care unit-acquired weakness. Charlson ME. Orfanos S. Examining the positive effects of exercise in intubated adults exercise that may have occurred in addition to direct observations. Conclusion The use of a mobility protocol promoted both earlier initiation and increased progression of exercise. Livaditi O. Ferdinande P. Dr. Zeger SL. Surgical intensive care unit mobility is increased after institution of a computerized mobility order set and intensive care unit mobility protocol: a prospective cohort analysis. coordination and oversight. Bernard GR. inclusion of these variables in future work would add important information to the utility of early progressive mobility.+Model YICCN-2227. suggesting that brief episodes of low-intensity exercise positively altered inﬂammatory dysregulation in this sample. Chambers MA. KP collected data. Truman B. Daly was supported by the Department of Veterans Affairs. Langer D. Respirology 2006. Inter-rater reliability of manual muscle strength testing in ICU survivors and simulated patients. Contributions CW carried out the grant application. et al. Staff in the Medical and Surgical ICUs at University Hospitals. neither consulted for or received compensation from the hospital or Hill-Rom related to purchases. Journal of Biomedicine and Biotechnology 2010 [Epub520258]. Fan E.11(6):715—22.36(6):1038—43.35(1):139—45. Less than 5% of exercise periods were associated with a concerning increase in respiratory rate or peripheral oxygen desaturation. contributing to the design of the data collection forms and initial format of the database.76(8):818—22. Blair R.41(3):263—7. Robbeets C. Reid MB. Yang PC.35(1):1—3. May L. Examining the positive effects of exercise in intubated adults in ICU: A prospective repeated measures clinical study. Intensive Crit Care Nurs (2012). Moylan JS.):S337—46. PhD. Critical Care Medicine 2007.37(10 Suppl. KJ participated in data management and analysis and helped to draft the manuscript.40:373—83. served as the initial project manager. No. Critical Care Medicine 2010. Hall JB. physical therapists and respiratory therapists. doi:10. The scope of the study did not include collection of data about readmission and post-ICU outcomes. Miller PR.37(9):2499—505. Journal of the American Medical Association 2001. Chen WC. and edited the draft and ﬁnal manuscript.02. Ales KL. Building consensus on ICU-acquired weakness. Ely EW. Spuhler VJ. Bhoopathi V. Early exercise in critically ill patients enhances short-term functional recovery. Needham DM.and antiinﬂammatory cytokine levels and outcome prediction in unselected critically ill patients. staff from Hill-Rom did not participate in the project design. a component of the National Institutes of Health and NIH roadmap for Medical Research. Hildreth AN. Troosters T. Critical Care Medicine 2009. Brandt C. New Hill-Rom beds were purchased by ICUs during the study but neither CW nor KP were involved in the process of identifying or selecting ICU equipment. Temporal changes in cytokine/chemokine proﬁles and pulmonary involvement in severe acute respiratory syndrome. The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. et al. These results should encourage additional study of exercise therapies for the care of patients experiencing prolonged mechanical ventilation in the ICU. assisted with data management and interpretation. Athanasiou C. and drafted the manuscript. Enniss T. All authors read. avoiding clinician inertia and long periods of uninterrupted bed rest in intubated adults. Martin RS. Hill-Rom provided salary support and funding for cytokine analyses. Acknowledgements This publication was made possible by the Case Western Reserve University/Dahms Clinical Resource Unit at University Hospitals.286:2703—10. The study was funded by Hill-Rom. Ofﬁce of Rehabilitation Research and Development. Pompei P. Case Medical Center M01 RR00080 and UL1 RR24989 from the National Center for Research Resources. References Bailey P. Pedersen BK. Chien JY. This report suggests a relatively limited intervention of one 20-minute episode of exercise daily for two or more days initiated by a nurse can demonstrate a signiﬁcant reduction in ICU LOS. Inouye SK. The study began prior to hospital equipment review and purchase. et al. data analysis or interpretation. et al. coordinated study implementation.007 . and approved the ﬁnal manuscript. Cytokine 2008. Grifﬁths RD. including nurses. Jewkes J. et al. Bexdihan L. Derlirium in mechanically ventilated patients: validity and reliability of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). GiamarellosBourboulis E. Its contents are solely the Please cite this article in press as: Winkelman C. Emily Liou. of Pages 12 ARTICLE IN PRESS 11 responsibility of the authors and do not necessarily represent the ofﬁcial view of NCRR or NIH. AL participated in study design and in interpreting the cytokine ﬁndings. Burtin C. Turong AD. Kotanidou A. Intensive Care Medicine 2009. Case Medical Center.38(3):779—87. Thomsen GE. Intensive Care Medicine 2010. Duration of exercise was linked to an increase in IL-10. JD participated in study design and study staff training and manuscript development. both CW and KP received salary support for the study.
17(4):271—81. Derivation and validation of SpO2 /FiO2 ratio to impute for PaO2 /FiO2 ratio in the respiratory component of the Sequential Organ Failure Assessment score.2012. critically ill patients: a randomised controlled trial.7(2):200—4. et al. Critical Care 2009. Critical Care Medicine 2010. Journal of Critical Care 2009. Ely EW.25(1). et al. Winkelman C.209(3):320—31. Schweickert WD. Sanders NW. Kalisch BJ. Ventilator-associated pneumonia or not? Contemporary diagnosis. The surgical intensive care unit optimal score predicts mortality and length of stay. et al. Phillips AC. Emerging Infectious Diseases 2001. Sulibruk JW.com. Morris PE. Thomsen GE. Lee KH. Progress in the development of the index of ADL. Early cytokine production risk stratiﬁes trauma patients for multiple organ failure.14(5):449 [author reply 449]. Shintani AK. Dittus RS. Cash HR. Vollman KM. Chen YJ.10(1):20—30. Higgins PA. Pradham P. 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