Inactivity and Inflammation in the Critically Ill Patient

doi:10.1016/j.ccc.2006.11.002

Critical Care Clinics

Volume 23, Issue 1, January 2007, Pages 21-34

https://doi.org/10.1016/j.ccc.2006.11.002 Get rights and content

Bed rest is a commonly prescribed activity restriction among patients in the ICU. Although bed rest may promote rest, recovery and safety, inactivity related to bed rest also may lead to complications and adverse outcomes. The biological mechanisms that lead to immediate and long-term sequelae from bed rest have not been elucidated. It may be the inflammatory factors common to critical illness combined with bed rest lead to a positive feedback loop, contributing to inflammatory disequilibrium. This disequilibrium has a profound affect on muscles. Muscle decay has serious and long-term adverse outcomes on survivors of critical illness. Mobility therapy may improve inflammatory disequilibrium and preserve muscles, leading to improved functional outcome. Investigations in the laboratory, in healthy people and among patients with systemic inflammatory disease, suggest that activity does not exacerbate inflammation. Clinically, exercise is beneficial to patients with various chronic inflammatory diseases. Further study is needed to best understand the role, duration, and frequency of activity in promoting recovery for critically ill patients.

Section snippets

Inactivity and muscle dysfunction

Deconditioning is defined as the multiple changes in organ systems that are caused by inactivity [24]. Heart, lung, and muscle deconditioning have been studied extensively. In normal, healthy subjects, there are immediate neuromuscular effects related to inactivity. For example, within 4 hours of bed rest, muscles deteriorate [3]. Sarcomeres are reduced, shortening muscle fibers and total muscle length. There is a loss of contractile force resulting in decreased strength. With a daily loss of

Oxidants, cytokines, and myopathy

Some evidence suggests that inactivity can contribute to imbalances in the inflammatory response [41], [42]. Both oxidative stress and proinflammatory cytokines have been investigated as potential causes for myopathy during acute and critical illness. It may be that there is a synergy between oxidative stress, inflammatory cytokines, and inactivity such that atrophy is accelerated or compounded. If true, then there are important implications for clinicians in terms of preventative and

Oxidants, cytokines, and activity

There are few published data about the effect of exercise activities on oxidants or cytokines in critically ill patients [10]. Some clinicians may believe that ICU patients may not be able to perform activity or mobility therapy at sufficient intensity to produce effects locally (ie, within the muscle) or systemically. Yet studies of healthy adults suggest that low and moderate levels of activity produce measurable physiological changes measured in muscle biopsies and plasma values. In the ICU

Summary

It is common for patients in the ICU to experience bed rest, sometimes for prolonged periods. Bed rest may be a natural consequence of illness and beneficial for recovery. Inactivity, however, especially during prolonged illness, contributes to muscle loss and decrements in functional status. Bed rest among ICU patients has had limited investigation. The duration and body positions that produce optimal outcomes related to a prescription of bed rest are not known. The mode, duration, and

References (102)

K. Stiller
Physiotherapy in intensive care: towards an evidence-based practice
Chest
(2000)
C. Allen et al.
Bed rest: a potentially harmful treatment needing more careful evaluation
Lancet
(1999)
R.R. Bergel
Disabling effects of inactivity and importance of physical conditioning. A historical perspective
Rheum Dis Clin North Am
(1990)
B.D. Duscha et al.
Deconditioning fails to explain peripheral skeletal muscle alterations in men with chronic heart failure
J Am Coll Cardiol
(2002)
M.A. Smith et al.
Redox modulation of contractile function in respiratory and limb skeletal muscle
Respir Physiol Neurobiol
(2006)
N.R. MacIntyre et al.
Management of patients requiring prolonged mechanical ventilation: report of a NAMDRC consensus conference
Chest
(2005)
V.A. Pavlov et al.
The cholinergic anti-inflammatory pathway
Brain Behav Immun
(2005)
R.C.J. Langen et al.
Serial review: role of reactive oxygen and nitrogen species (ROS/RNS) in lung injury and diseases
Free Radic Biol Med
(2003)
L. Flohe et al.
Redox regulation of NF-kappa B activation
Free Radic Biol Med
(1997)
Y.M. Janssen-Heininger et al.
Recent advances towards understanding redox mechanisms in the activation of nuclear factor kappa B
Free Radic Biol Med
(2000)

E.M. Simmons et al.

Plasma cytokine levels predict mortality in patients with acute renal failure

Kidney Int

(2004)

M.B. Reid et al.

Redox mechanisms of muscle dysfunction in inflammatory disease

Phys Med Rehabil Clin N Am

(2005)

C. Dinarello

Interleukin-1 family

G. Yang et al.

Repetitive mechanical stretching modulates IL-1beta-induced COX-2, MMP-1 expression and PGE2 production in human patellar tendon fibroblasts

Gene

(2005)

R.J. Gassner et al.

Interaction of strain and interleukin-1 in articular cartilage: effects on proteoglycan synthesis in chondrocytes

Int J Oral Maxillofac Surg

(2000)

Y. Ding et al.

Interleukin-10

S. Adamopoulos et al.

Physical training modulates proinflammatory cytokines and the soluble Fas/soluble Fas ligand system in patients with chronic heart failure

J Am Coll Cardiol

(2002)

A.I. Larsen et al.

Effect of exercise training on skeletal muscle fibre characteristics in men with chronic heart failure. Correlation between skeletal muscle alterations, cytokines, and exercise capacity

Int J Cardiol

(2002)

P.V. Ennezat et al.

Physical training in patients with chronic heart failure enhances the expression of genes encoding antioxidative enzymes

J Am Coll Cardiol

(2001)

E. Goldhammer et al.

Exercise training modulates cytokine activity in coronary heart disease patients

Int J Cardiol

(2005)

A.C. Guyton et al.

Textbook of medical physiology

(2006)

A.J. Sargeant et al.

Functional and structural changes after disuse of human muscle

Clin Sci (Colch)

(1977)

C. Kasper et al.

Skeletal muscle damage and recovery

AACN Clin Issues

(2002)

V.A. Convertino et al.

An overview of the issues: physiological effects of bed rest and restricted physical activity

Med Sci Sports Exerc

(1997)

M.C. Creditor

Hazards of hospitalization of the elderly

Ann Intern Med

(1993)

I. Bautmans et al.

Circulating acute-phase mediators and skeletal muscle performance in hospitalized geriatric patients

J Gerontol A Biol Sci Med Sci

(2005)

S. Krishnagopalan et al.

Body positioning of intensive care patients: clinical practice versus standards

Crit Care Med

(2002)

C. Winkelman et al.

Activity in the chronically critically ill

Dimens Crit Care Nurs

(2005)

B.J. Kalisch

Missed nursing care: a qualitative study

J Nurs Care Qual

(2006)

C.M. Harper et al.

Physiology and complications of bed rest

J Am Geriatr Soc

(1988)

S.D. Mentzelopoulos et al.

Static pressure volume curves and body posture in acute respiratory failure

Intensive Care Med

(2005)

S.M. Burns et al.

Effect of body position on spontaneous respiratory rate and tidal volume in patients with obesity, abdominal distention, and ascites

Am J Crit Care

(1994)

M. Rubin

The physiology of bed rest

Am J Nurs

(1988)

J.R. Peerless et al.

Skin complications in the intensive care unit

Clin Chest Med

(1999)

E.V. Carlson et al.

Predicting the risk of pressure ulcers in critically ill patients

Am J Crit Care

(1999)

S.M. Fortney et al.

The physiology of bedrest

E.W. Ely et al.

Delirium in the intensive care unit: an under-recognized syndrome of organ dysfunction

Semin Respir Crit Care Med

(2001)

M.J. Mador et al.

Skeletal muscle dysfunction in chronic obstructive pulmonary disease

Respir Res

(2001)

N.L. Szaflarski

Immobility phenomena in critically ill adults

F.L. Oliver

Suggested guidelines for the use of exercise with adults in acute care settings: a computerized key work search

Physiother Can

(1998)

R. Topp et al.

The effect of bed rest and potential of prehabilitation on patients in the intensive care unit

AACN Clin Issues

(2002)

S. Yende et al.

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well-functioning elderly subjects

Thorax

(2006)

C. Hall et al.

Therapeutic exercise: moving toward function

(1999)

K.J. Tracey

The inflammatory reflex

Nature

(2002)

C.J. Czura et al.

Autonomic regulation of immunity

J Intern Med

(2005)

M.M. Mallis et al.

Circadian rhythms, sleep, and performance in space

Aviat Space Environ Med

(2005)

S. Mott et al.

Physical and chemical restraints in acute care: their potential impact on rehabilitation of older people

Int J Nurs Pract

(2005)

L.S. Aaronson et al.

Use of health records in research: reliability and validity issues

Res Nurs Health

(1994)

B.A. St. Pierre et al.

Fatigue mechanisms in patients with cancer: effects of tumor necrosis factor and exercise on skeletal muscle

Oncol Nurs Forum

(1992)

E.J. Corwin

Understanding cytokines part I: physiology and mechanism of action

Biol Res Nurs

(2000)

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2021, Archives of Physical Medicine and Rehabilitation
To examine the effects of intensive rehabilitation on mortality and liberation from mechanical ventilation among patients with mechanical ventilation in intensive care units.
Retrospective cohort study using the Diagnosis Procedure Combination inpatient database.
Patients discharged from acute care hospitals from April 2010 to March 2016.
Patients (N=46,438) aged 20 years and older who were admitted to intensive care units and who started rehabilitation within 3 days of starting mechanical ventilation.
Intensive rehabilitation in intensive care unit in the first 5 days after admission. Amount of rehabilitation was defined as the average number of units per day in the first 5 days after admission and was dichotomized as intensive (≥1.0 unit/d) or nonintensive (<1.0 unit/d) rehabilitation.
The primary outcome was in-hospital mortality. The secondary outcome was liberation from mechanical ventilation.
We identified 29,982 eligible patients, including intensive (n=7745) and nonintensive (n=22,237) rehabilitation groups. In the propensity score-matched analysis, the intensive rehabilitation group had significantly lower in-hospital mortality (risk difference: −3.4%; 95% CI, −4.9% to −1.9%) and a higher proportion of liberation from mechanical ventilation (subdistribution hazard ratio, 1.08; 95% CI, 1.03-1.13) compared with the nonintensive rehabilitation group.
Patients receiving a higher amount of rehabilitation in intensive care units were less likely to die and more likely to be liberated from mechanical ventilation.
Effects of Inspiratory Muscle Training and Early Mobilization on Weaning of Mechanical Ventilation: A Systematic Review and Network Meta-analysis
2020, Archives of Physical Medicine and Rehabilitation
Citation Excerpt :
Prolonged bed rest in critically ill patients promotes inflammatory mediators, a proinflammatory state, increased oxidative stress, and decreased antioxidative defences.89 Immobility is associated with limb muscle weakness, lung atelectasis, cardiopulmonary instability,13,55 increased protein degradation, and decreased mitochondrial density in respiratory muscles.76,90 During exercise, interleukin-6 stimulates the appearance in the circulation of interleukin-10, which is an anti-inflammatory cytokine.91
To compare the effectiveness and rank order of physical therapy interventions, including conventional physical therapy (CPT), inspiratory muscle training (IMT), and early mobilization (EM) on mechanical ventilation (MV) duration and weaning duration.
PubMed, The Cochrane Library, Scopus, and CINAHL complete electronic databases were searched through August 2019.
Randomized controlled trials (RCTs) investigating the effect of IMT, EM, or CPT on MV duration and the weaning duration in patients with MV were included. Studies that were determined to meet the eligibility criteria by 2 independent authors were included. A total of 6498 relevant studies were identified in the search, and 18 RCTs (934 participants) were included in the final analysis.
Data were extracted independently by 2 authors and assessed the study quality by the Cochrane risk-of-bias tool. The primary outcomes were MV duration and weaning duration.
Various interventions of physical therapy were identified in the eligible studies, including IMT, IMT+CPT, EM, EM+CPT, and CPT. The data analysis demonstrated that compared with CPT, IMT+CPT significantly reduced the weaning duration (mean difference; 95% confidence interval) (−2.60; −4.76 to −0.45) and EM significantly reduced the MV duration (−2.01; −3.81 to −0.22). IMT+CPT and EM had the highest effectiveness in reducing the weaning duration and MV duration, respectively.
IMT or EM should be recommended for improving the weaning outcomes in mechanically ventilated patients. However, an interpretation with caution is required due to the heterogeneity.
Tai chi for enhanced inpatient mobilization: A feasibility study
2019, Complementary Therapies in Medicine
To determine whether utilizing beginner, video-guided tai chi and qigong classes as an adjunct to physical therapy to enhance mobilization among hospitalized patients is feasible and acceptable.
Single-arm feasibility study over a 15½-week period.
Three medical-surgical units at one hospital.
Small-group video-guided beginner-level tai chi and qigong classes supervised by physical therapists occurred three times a week.
The primary outcome was weekly class attendance. Secondary outcomes included patient and staff satisfaction, collected by surveys and semi-structured interviews. Process measures included class duration. Balancing measures included falls.
One-hundred and fifty-seven patients were referred for recruitment, 45 gave informed consent, and 38 patients attended at least one class. The number of weekly class attendees increased during the study period. Based on first-class experience, 68% (26/38) of patients reported enjoying the class “quite a bit” or “extremely,” 66% (25/38) of patients reported feeling “more mobile” afterward, and 76% (29/38) of patients agreed that the class made them more comfortable going home. Average class duration was 29 minutes. Zero falls occurred during or immediately following class.
Video-guided tai chi and qigong classes are feasible and well-received at our hospital. Future studies of the impact on preserving mobility and function or reducing length of stay are of interest.
Early mobility in frail and non-frail older adults admitted to the cardiovascular intensive care unit
2018, Journal of Critical Care
Citation Excerpt :
Catheter dislodgement and transient physiologic changes are the most commonly reported complications. Yet despite the demonstrated effectiveness and safety in the peer-reviewed literature for EM practices in critical care units, there is evidence that actual practice is lacking [33]. A recent survey of physicians working in critical care units reported that, while more than half of physicians believed that mobilization should begin as early as possible after unit admission, almost three-quarters felt that they lacked adequate knowledge or training to mobilize patients [34].
Little is known about the effects of early mobilization in older adults in the Cardiovascular Intensive Care Unit (CICU).
We reviewed consecutive patients ≥60 years of age admitted to the CICU at an academic tertiary care center from 2016 to 2017. The level of function (LOF) was assessed prehospital, at CICU admission, and at CICU transfer using a graded scale ranging from LOF 1 (bedbound) to 4 (walk > 50 ft). The prehospital frailty status was assessed using Rockwood's Clinical Frailty Scale. We sought to determine whether the mean change of LOF during CICU admission differed based on frailty status.
There were 264 patients in the cohort (77.1 ± 9.3 years old; 40% female; 34% frail). Frail patients were more likely to have lower prehospital, CICU admission, day of transfer LOFs (all P < 0.001). The mean LOF improvement during CICU stay was 0.5 ± 0.8 and did not differ based on frailty status. Frailty was not predictive of EM responsiveness in the adjusted analysis.
EM is feasible in older adults admitted to the CICU. Functional status improved in both frail and non-frail older adults during CICU admission. Prospective studies are needed to determine whether frail older adults may benefit from EM.
Influence of muscle strength on early mobility in critically ill adult patients: Systematic literature review
2018, Heart and Lung: Journal of Acute and Critical Care
Citation Excerpt :
Muscle weakness, prevalent in the critically ill patient, is multi-factorial in its causes and may be compounded by neuromuscular, cardiovascular, pulmonary, psychological, pharmacological and equipment barriers.9,21,27
Muscle strength may be one indicator of readiness to mobilize that can be used to guide decisions regarding early mobility efforts and to progressively advance mobilization.
To provide a synthesis of current measures of muscle strength in the assessment of early mobilization in critically ill adult patients who are receiving MV therapy.
Research studies conducted between 2000-2015 were identified using PubMed, CINHAL, MEDLINE, and the Cochrane Database of Systematic Reviews databases using the search terms “muscle strength”, “intensive care”, “mechanical ventilation” and “muscle weakness”.
Nine articles used manual muscle testing, the Medical Research Council scale and/or hand-held dynamometer to provide objective measures for assessing muscle strength in the critically ill adult patient population.
Further research is needed to examine the application of standardized measures of muscle strength for guiding decisions regarding early and progressive advancement of mobility goals in adult ICU patients on MV.
Oxidative stress and immune system analysis after cycle ergometer use in critical patients
2017, Clinics
Citation Excerpt :
Apart from its proinflammatory properties, high levels of IL-6 act to stimulate the emergence of antiinflammatory cytokines in the plasma, including IL-10 and IL-1R α. IL-6 derived from muscles reduces the production of TNF-α, interrupting the muscle degradation through the destruction of myosin 18. The abolition of proinflammatory cytokines such as IL-6, particularly the powerful IL-β 1 and TNF-α, can benefit the critically ill.
The passive cycle ergometer aims to prevent hypotrophy and improve muscle strength, with a consequent reduction in hospitalization time in the intensive care unit and functional improvement. However, its effects on oxidative stress and immune system parameters remain unknown. The aim of this study is to analyze the effects of a passive cycle ergometer on the immune system and oxidative stress in critical patients.
This paper describes a randomized controlled trial in a sample of 19 patients of both genders who were on mechanical ventilation and hospitalized in the intensive care unit of the Hospital Agamenom Magalhães. The patients were divided into two groups: one group underwent cycle ergometer passive exercise for 30 cycles/min on the lower limbs for 20 minutes; the other group did not undergo any therapeutic intervention during the study and served as the control group. A total of 20 ml of blood was analysed, in which nitric oxide levels and some specific inflammatory cytokines (tumour necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and interleukins 6 (IL-6) and 10 (IL-10)) were evaluated before and after the study protocol.
Regarding the demographic and clinical variables, the groups were homogeneous in the early phases of the study. The nitric oxide analysis revealed a reduction in nitric oxide variation in stimulated cells (p=0.0021) and those stimulated (p=0.0076) after passive cycle ergometer use compared to the control group. No differences in the evaluated inflammatory cytokines were observed between the two groups.
We can conclude that the passive cycle ergometer promoted reduced levels of nitric oxide, showing beneficial effects on oxidative stress reduction. As assessed by inflammatory cytokines, the treatment was not associated with changes in the immune system. However, further research in a larger population is necessary for more conclusive results.

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Inactivity and Inflammation in the Critically Ill Patient

Section snippets

Inactivity and muscle dysfunction

Oxidants, cytokines, and myopathy

Oxidants, cytokines, and activity

Summary

Chest

Lancet

Rheum Dis Clin North Am

J Am Coll Cardiol

Respir Physiol Neurobiol

Chest

Brain Behav Immun

Free Radic Biol Med

Free Radic Biol Med

Free Radic Biol Med

Kidney Int

Phys Med Rehabil Clin N Am

Gene

Int J Oral Maxillofac Surg

J Am Coll Cardiol

Int J Cardiol

J Am Coll Cardiol

Int J Cardiol

Textbook of medical physiology

Functional and structural changes after disuse of human muscle

Clin Sci (Colch)

Skeletal muscle damage and recovery

AACN Clin Issues

An overview of the issues: physiological effects of bed rest and restricted physical activity

Med Sci Sports Exerc

Hazards of hospitalization of the elderly

Ann Intern Med

Circulating acute-phase mediators and skeletal muscle performance in hospitalized geriatric patients

J Gerontol A Biol Sci Med Sci

Body positioning of intensive care patients: clinical practice versus standards

Crit Care Med

Activity in the chronically critically ill

Dimens Crit Care Nurs

Missed nursing care: a qualitative study

J Nurs Care Qual

Physiology and complications of bed rest

J Am Geriatr Soc

Static pressure volume curves and body posture in acute respiratory failure

Intensive Care Med

Effect of body position on spontaneous respiratory rate and tidal volume in patients with obesity, abdominal distention, and ascites

Am J Crit Care

The physiology of bed rest

Am J Nurs

Skin complications in the intensive care unit

Clin Chest Med

Predicting the risk of pressure ulcers in critically ill patients

Am J Crit Care

The physiology of bedrest

Delirium in the intensive care unit: an under-recognized syndrome of organ dysfunction

Semin Respir Crit Care Med

Skeletal muscle dysfunction in chronic obstructive pulmonary disease

Respir Res

Immobility phenomena in critically ill adults

Suggested guidelines for the use of exercise with adults in acute care settings: a computerized key work search

Physiother Can

The effect of bed rest and potential of prehabilitation on patients in the intensive care unit

AACN Clin Issues

Inflammatory markers are associated with ventilatory limitation and muscle dysfunction in obstructive lung disease in well-functioning elderly subjects

Thorax

Therapeutic exercise: moving toward function

The inflammatory reflex

Nature

Autonomic regulation of immunity

J Intern Med

Circadian rhythms, sleep, and performance in space

Aviat Space Environ Med

Physical and chemical restraints in acute care: their potential impact on rehabilitation of older people

Int J Nurs Pract

Use of health records in research: reliability and validity issues

Res Nurs Health

Fatigue mechanisms in patients with cancer: effects of tumor necrosis factor and exercise on skeletal muscle

Oncol Nurs Forum

Understanding cytokines part I: physiology and mechanism of action

Biol Res Nurs