Intensive care unit–acquired weakness is a frequent complication of critical illness because of patients’ immobility and prolonged use of mechanical ventilation.
To describe daily measurements of peripheral muscle strength in patients receiving mechanical ventilation and explore relationships among factors that influence intensive care unit–acquired weakness.
Peripheral muscle strength of 120 critically ill patients receiving mechanical ventilation was measured daily by using a standardized handgrip dynamometry protocol. Three grip measurements for each hand were recorded in pounds-force; the mean of these 3 assessments was used in the analysis. Correlates of intensive care unit–acquired weakness (age, sex, illness severity, duration of mechanical ventilation, medications) were analyzed by using mixed models to explore the relationship to grip strength.
Median baseline grip strength was variable yet diminished (7.7 pounds-force), with either a pattern of diminishing grip strength or maintenance of the baseline low grip strength over time. With controls for days of measurement, female sex (β = −10.4; P < .001), age (β = −0.24; P = .004), and days receiving mechanical ventilation (β = −0.34; P = .005) explained a significant amount of variance in grip strength over time.
Patients receiving prolonged mechanical ventilation had marked decrements in grip strength, measured by hand dynamometry, a marker for peripheral muscle strength. Hand dynamometry is a reliable method for measuring muscle strength in cooperative critically ill patients and can be used to develop interventions to prevent intensive care unit–acquired weakness.
Intensive care unit (ICU)–acquired weakness, defined as the development of severe paresis related to critical illness,1 is a frequent complication of critical illness because of patients’ prolonged immobility and bed rest,2 particularly in patients receiving prolonged mechanical ventilation.1 Respiratory and limb muscle strength are altered after 7 days of mechanical ventilation, leading to delayed extubation and prolonged mechanical ventilation.3 Development of ICU-acquired weakness can also contribute to physical limitations in patients who recover from critical illness.1,2
Known risk factors for ICU-acquired weakness include older age, sepsis, electrolyte disturbances, receipt of corticosteroids and neuromuscular blocking agents, illness severity, and immobility; an indirect link has been proposed for sedation because of the reduced mobility of sedated patients.4 (p In addition, muscle mass and force of muscle contraction decrease with age, resulting in weakness that exceeds what would be expected in a patient with muscle atrophy.5 In one study,6 being female was significantly associated with ICU-acquired weakness. Of these known risk factors, ones that are not clinically modifiable include older age, sex, multisystem organ failure, sepsis, and the requirements of some patients for medications such as corticosteroids and neuromuscular blocking agents.7 Modifiable risk factors include hyperglycemia and use of sedatives.7
Little is known about the pattern of muscle strength during mechanical ventilation, or if modifiable risk factors might directly influence muscle strength in patients experiencing prolonged mechanical ventilation. Measurement of muscle strength is also difficult in the critical care unit because noninvasive methods require alert and cooperative patients. One objective, directly quantifiable measure of peripheral muscle strength is handgrip dynamometry. Grip strength limited to 1 to 3 measurements has been used by other ICU researchers1,4 as a marker of impaired functional status, with diminished grip strength linked to increased ICU mortality.1 Few data are available on serial assessments of grip strength during mechanical ventilation. Thus, the purpose of this longitudinal study was to describe serial measurements of peripheral muscle strength and to identify factors associated with patterns of peripheral muscle strength during mechanical ventilation.
Patients included in this descriptive, correlational study were a subset (n = 120) of patients receiving mechanical ventilation who were enrolled in a randomized clinical trial on self-management of anxiety with preferred, relaxing music.8 Participants were recruited from 12 ICUs in 5 hospitals associated with the University of Minnesota, Minneapolis, Minnesota, and were receiving mechanical ventilation for a primary pulmonary problem.
Patients were enrolled from ICUs where care was delivered at the bedside by registered nurses in a 1 to 2 or 1 to 1 nurse to patient ratio. All of the participating ICUs had a written sedation administration protocol; however, protocols varied among sites. None of the participating ICUs had progressive mobility protocols in place at the time of enrollment. Patients remained enrolled in the parent study as long as they were receiving mechanical ventilation, up to 30 days; or until they were extubated, chose to withdraw from the study, were transferred from the ICU, or died. Patients were enrolled in the parent study for a mean of 5.7 days (SD, 6.4; median, 3.2; range 1–30).8
Patients met inclusion criteria if they were making their own daily care decisions, were interacting appropriately with staff, had stable hemodynamic status, and were not currently receiving paralytic medications. Patients provided their own consent because of the patient-directed nature of the intervention protocol. This study was approved by the human subjects’ committees of the University of Minnesota and the participating sites. Details on the parent study have been reported elsewhere.8
Grip-Strength Measurement via Hand Dynamometry
Peripheral muscle strength was determined by using handgrip dynamometry with the Jamar Hydraulic Hand Dynamometer (Patterson Medical), which measures the force or strength of a grip in pounds-force. The Jamar hand dynamometer is considered the standard for measurement of grip strength because of its high calibration accuracy at ±3% to 5%.9,10 The standardized normal grip strength for adults is 101 to 121 pounds-force for men and 57 to 70 pounds-force for women,9 providing a quantifiable measure for comparison.
Research by Mathiowetz and collegues9,11 has resulted in a standard protocol for assessing grip strength, which includes patient positioning and how to give verbal instructions for completing the assessment. Grip-strength measurements are more accurate when the mean of 3 grip trials is used rather than either a single grip trial or the highest reading of 3 trials.9,11 Mathiowetz and colleagues9,11 have reported high interrater reliability (right grip, r = 0.99; left grip, r = 0.99) and high test-retest reliability when the mean of 3 grip trials is used (right grip, r = 0.88; left grip, r = 0.93). No significant problems with variability in having multiple people performing assessments have been identified.11
Because the original measurement standards were developed with healthy persons in a seated position, an occupational therapist was consulted to modify the protocol for the patients in this study. Research nurses were trained by the occupational therapist in the Mathiowetz assessment procedure (Table 1). One Jamar device was stored at each hospital to ensure that patients used the same device throughout the study. Baseline handgrip strength was evaluated on the day of enrollment into the parent study and then assessed daily by using the protocol (Table 1). Hand dynamometry was discontinued for any day when a patient expressed any indications of pain or declined to complete the grip assessments.
Patients were approached for grip-strength measurement each day they were enrolled in the parent study. If a patient was not able to generate any grip strength on the Jamar dial, a value of zero was recorded for that day. If a patient was off the unit, unable to participate in measurement, or declined grip measurement, no value was recorded for that day.
Correlates of ICU-Acquired Weakness
Known correlates of ICU-acquired weakness explored were limited to correlates available from the parent study. Patient characteristics included risk and protective factors such as age, sepsis, receipt of corticosteroids, continuous insulin infusion, any receipt of neuromuscular blocking agents, and illness severity. The Acute Physiology and Chronic Health Evaluation III was used to measure illness severity. Scores on the evaluation were calculated on the basis of the ICU admission data. The higher the score (range, 0–299), the more ill a patient is and the higher the risk of ICU mortality.12
Use of sedatives throughout study enrollment allowed for summarizing dose frequency, termed sedation frequency over 24 hours, and aggregate dose of medications, termed sedation intensity score (SIS), from disparate drug classes.13 Eight commonly administered analgesics or sedatives (midazolam, lorazepam, fentanyl, morphine, dexmedetomidine, hydromorphone, propofol, haloperidol) were monitored, and a weight-adjusted dose for each medication administered during a 4-hour time block was calculated. A patient’s mean SIS (quotient of sum of patient’s SIS values and number of 4-hour intervals receiving mechanical ventilation) represents the mean sedative exposure per hour relative to all other patients. Details on calculating sedative exposure can be found elsewhere.8,13
Descriptive statistics (frequencies for categorical data, measures of central tendency and dispersion), graphing, and mixed modeling were used to analyze the data. Mixed-effects models were used to analyze grip strength over time to accommodate data that were correlated and data that had variances that were not constant from one time point to another and to accommodate any missing values. When the data are used as they are, without imputation, within a mixed model, analysis has a lower type I error and higher power than with any type of imputation method used for missing data, which may result in biased estimates of effects and standard errors.
Possible patterns of change were explored by graphing each patient’s grip strength vs time. Sedation patterns were also explored by graphing the SIS and sedation frequency by patient over time. The patients had a linear change over time, with a predominantly negative slope for grip strength, although variation did occur. An unconditional means model was used to assess 2 null hypotheses: no change across occasions and no variation between patients. Rejection of these null hypotheses warrants further analysis.
Determination of parameters and a final mixed-effects model proceeded as follows. First, an unconditional growth model was developed with Day added as a predictor that resulted in estimation of change coefficients. The best-fitting covariance structure was the autoregressive covariance structure with the assumption that correlations decrease as the lag time increases. Next, a conditional growth model introduced the effect of the covariates that were both associated with grip strength and clinically important, such as an effect from sedation (SIS). An unstructured covariance structure was the best fit for this analysis.
SPSS, version 17 (IBM SPSS), and SAS, version 9.2 (SAS Institute Inc), software were used for analyses. Level of significance was determined a priori as P ≤ .05.
Description of Patients
The patients in this study were mostly white women (51%) with a median age of 52 years. Most patients’ indication for mechanical ventilation was respiratory failure (50%). Only 6.5% of patients had a diagnosis of sepsis, 38% received continuous insulin infusions, 56% received corticosteroids, and 10% received neuromuscular blocking agents. Patients were enrolled for a median of 4.2 (range, 1–30) days. Median number of days receiving mechanical ventilation before enrollment in the study was 6.7, with a median of 9 days in the ICU before enrollment. Disposition of patients at ICU discharge was 92% alive and 8% deceased (see Table 2 for details).
Median baseline grip strength was quite diminished, at 7.7 pounds-force, with a wide range, from 0 to 102 pounds-force (Table 2). A few patients (n = 6) could not generate any grip strength (zero on the Jamar dial) despite coaching and encouragement from research staff.
The median number of grip-strength measurements for patients was 4 (range, 0–30). As shown in Figure 1, the pattern of grip strength during mechanical ventilation indicates that patients either start at a higher grip strength and then their strength declines, or they start at a lower point and either stay at that diminished level or their strength continues to decline further over time. Only 3 patients had a pattern of increasing grip strength.
Figure 2 indicates median grip strength over time by sex. The data show a fluctuating pattern of grip strength over time in both men and women. By the end of the study, the data suggest a possible upward trend in grip strength as patients recover from a prolonged critical illness.
Median overall SIS was 4 (range, 0–11), median dose frequency was 6.4 (range, 0–16) each study day, and 26% of patients received continuous infusions of sedatives or opiates.
Correlates Among Grip Strength, Patient Characteristics, and Sedative Exposure
Level 1 modeling showed significant unexplained variance in both grip strength over time (z = 5.41; P < .001) and in initial grip strength (z = 5.37; P < .001), indicating further analysis was appropriate. In level 2 modeling, with controls for days on protocol, being female (β = −10.4; SE, 2.5; P < .001), age (β = −0.24; SE, 0.08; P = .004), and days receiving mechanical ventilation (β = −0.34; SE, 0.12; P = .005) explained a significant amount of variance in grip strength over time (Table 3). Women started with a grip strength 10.4 pounds-force lower than the grip strength of men. For each year older a patient was, the grip strength diminished 0.24 pounds-force, and for each additional day of mechanical ventilation, grip strength decreased by 0.34 pounds-force. Scores on the Acute Physiology and Chronic Health Evaluation III (β = −0.12; SE, 0.07; P = .09), receipt of insulin, receipt of corticosteroids, sedative exposure, or neuromuscular blocking agents did not significantly contribute to an explanation of variance over time in grip strength.
We provide data on serial measurement of grip strength in ICU patients whose clinical status was fairly stable and whose severity of illness was low. A majority of the sample did not have sepsis. To be eligible for the parent study, patients had to be awake and interacting appropriately with nursing staff. Thus, daily measurement of grip strength was a reasonable approach for tracking peripheral muscle strength in these cooperative patients. Patients had significant decrements in peripheral muscle strength at baseline (median day 6.7 of mechanical ventilation). Baseline measures were substantially lower than the norms for men and women, and patients did not show any substantial improvement in grip strength over time.
Age, being female, and lengthy periods of mechanical ventilation contributed to diminished grip strength in our patients, regardless of illness severity. Our sample of patients had lower severity of illness scores than did patients in other studies1,4 in which grip strength was measured or in a study5 that revealed significant and sustained weakness in ICU survivors with acute respiratory distress syndrome. However, our results indicate decreases in peripheral muscle strength regardless of diagnosis or how ill a patient was upon ICU admission. Schweikert and Hall7 have suggested several areas for risk-factor modification in patients at risk for ICU-acquired weakness. Although glycemic control is one area with evidence of benefit, receipt of continuous insulin infusions did not affect grip strength in our study; however, we did not assess overall blood glucose control. Likewise, medications linked to evidence for harm, corticosteroids and neuromuscular blocking agents, were also not significant correlates in our study. One area of indirect evidence for the modification of ICU-acquired weakness is sedation-sparing protocols. Although sedative exposure did not significantly contribute to decrements in peripheral muscle strength in our study, it could have indirectly contributed to lengthy periods of mechanical ventilation, which was a significant correlate in our study.
Our study had several limitations. Generalizability of the findings is relevant only to those ICU patients with characteristics similar to the characteristics of our sample. We did not obtain any data on disability before ICU admission that could have affected assessments of grip strength. We did not know if patients were already weak and had decrements in muscle strength before ICU admission. We also did not know when and if patients regained their muscle strength or if they experienced any decreases in functional domains and quality of life. Likewise, we did not obtain any measurement of respiratory muscle strength, strength that may have influenced total duration of mechanical ventilation. Finally, assessment of grip strength during early stages of mechanical ventilation was challenging. We were able to enroll patients only around day 6 or 7 of mechanical ventilation, because of the inclusion criteria of the parent study. However, as clinical practice guidelines that call for minimizing sedation are more widely implemented, handgrip dynamometry may be a feasible option for tracking peripheral muscle strength over the entire course of mechanical ventilation.
Implications for Practice
Our findings provide additional evidence of the detrimental effects of prolonged mechanical ventilation and immobility in ICU patients. Older, female patients may require additional efforts to minimize ICU-acquired weakness during lengthy courses of ventilatory support. Mobility programs may be useful in addressing at least some of the decreases in peripheral muscle strength during mechanical ventilation; however, for mobility programs to be successful, patients must be awake and interactive. Nurses will need additional training in mobility programs and alternatives to sedative medications for symptom management to promote alert and interactive patients who can be involved in maintaining or even improving peripheral muscle strength while receiving mechanical ventilation.
The significant decreases in grip strength at the time of enrollment and the sustained decreases without improvement in peripheral muscle strength during the study period in our patients suggest urgency in instituting activity and mobility interventions. One place to start may be to omit the “early” label and institute a culture where more awake and engaged patients are the expectation, not the exception, thereby increasing opportunities for mobility interventions. Implementation of interventions that sustain or preserve muscle strength and muscle mass is needed. Because of the projected increase in the number of patients who will require prolonged mechanical ventilation by 202014 and the financial burden of providing care for these patients, these trends have important implications. Clinicians need to carefully examine ICU care processes and the marked burden of critical illness on survivors’ recovery. Innovative interventions and care processes beyond progressive mobility are needed.
Nurses need to take the lead in managing the care in several different ways for patients treated with mechanical ventilation. Nurses can facilitate development of mobility protocols, implementing and coordinating activity and out-of-bed interventions as soon as possible in a safe manner. Symptom management requires ongoing intervention with both pharmacological and nonpharmacological interventions15 to manage patients distressful signs and symptoms and promote increasing patient movement. All members of the multidisciplinary care team must take accountability and collaborate to develop and implement innovative strategies based on the best available evidence to promote muscle preservation in critically ill patients. This group of care providers includes physical and occupational therapists, who can optimize rehabilitation resources related to mobility, as well as physicians and respiratory therapists, who can optimize ventilatory management.
Implications for Future Research
In our study, older women who had prolonged periods of mechanical ventilation had the greatest decreases in grip strength, a marker of peripheral muscle strength. Future longitudinal studies are needed to evaluate the feasibility of performing handgrip assessments throughout the entire course of mechanical ventilation, the predictive value of handheld dynamometry on patients’ functional outcomes,16 and the usefulness of grip strength assessment in guiding intervention strategies.
Novel interventions to preserve muscle mass and strength in ICU patients need to be developed and tested. These strategies could include interventions that can be performed in the bed or in a chair to maintain or improve strength even when active mobility may not always be an option.
Innovative mobility protocols that are safe and do not place an unnecessary burden on the ICU staff are needed. Because of the demands of high-acuity care, staffing patterns, the increasing need for interdisciplinary support, and the aging of the nursing workforce, these factors need to be considered and supported when developing and testing new ICU care protocols.
Summary and Conclusions
ICU-acquired weakness is a common problem in patients receiving prolonged mechanical ventilation. Our findings add to the evidence on the detrimental influence of prolonged mechanical ventilation and immobility, particularly in older female patients. Understanding the causes, pathophysiology, and risks factors of ICU-acquired weakness is important for prevention.2 A recent review5 presents information on clinical phenotypes and possible molecular mechanisms of ICU-acquired weakness that may inform innovative treatments for patients. Multidisciplinary team efforts are needed to quantify ICU-acquired weakness throughout the course of mechanical ventilation and to develop interventions to prevent or at least minimize ICU-acquired weakness.
This research was performed at the University of Minnesota. Research sites were the University of Minnesota Medical Center, Abbott-Northwestern Hospital, North Memorial Medical Center, United Hospital, Regions Hospital, and Hennepin County Medical Center.
This study was supported in part by grant 1 R01 NR009295 from the National Institute of Nursing Research (L. Chlan, principal investigator) and by a grant from the University of Minnesota Medical Center, Fairview, Nursing Research Council (M. Tracy, principal investigator).
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