Rehabilitation in the ICU

Abstract

Prolonged stay in the ICU comes with a variety of sequelae evolving toward chronic conditions rendering rehabilitation a challenge for the medical staff and patients’ families. Functional impairment is physical (touching mainly mobility: weakness, atrophy), cognitive or beyond (dysphagia, chronic pain, risk of falls). Properly identifying the risk factors means addressing them in a preventive manner. The curative approach, due to fragmented trajectories and the controversies related to early mobilization and the dose of physical rehabilitation, is still subject to debate. Possible barriers to implementing rehabilitation protocols were identified as well as future research themes regarding new targets for interventions to be tested in large-scale randomized controlled trials.

1. Introduction

Progress made in critical care throughout recent years lead to an increase in survival rates and a greater number of post- ICU patients to care for. Surviving ICU does not mean a full return to the patients’ capacities before ‘the injury’ leading to admission. Critical care survivors, their caregivers and families are burdened with functional impairments (physical, psychological, cognitive and beyond), prompting the implementations of a rapid and challenging rehabilitation program.

Patients’ trajectories are various and fragmented, due to the type of injury precluding the ICU admission and the structures in place for the post-ICU care.

Recent research did not merely focus on survival, but also on the critical care survivors’ recovery in the subsequent months, potentially years to follow.

2. Outcomes after ICU stay

It comes naturally for the outcome of a critically ill patient to depend on the severity of his condition upon admission and before becoming critically ill, on the number of days he was cared for, but also heavily, on the type of ICU attendance he was submitted to, that is on the competency of the ICU in cause (be it an academic facility or not), on the professionalism (knowledge, training, skills, dedication, ethics) and the management of the facility.

Outcomes after being cared for in an ICU refer to: sequels, evolving toward a chronic critical condition, acquiring muscular asthenia or weakness, developing delirium or other forms of acute psychosis (which is reputed for being associated with a bad outcome), developing multiple organ system failure, sepsis or becoming a reservoir (a source) for hospital-acquired germs. And as if these were not enough, survivors complain also of joint stiffness, pain, loss of condition and hair loss, and more disturbing, of dysphagia, which is a real invalidating burden, very difficult to treat, often undiagnosed and leading to nutrition issues, to say nothing of loss of hearing, smell and taste. Moreover, the recovery phase could last for years [1].

Since 2012, “ICU-acquired weakness” was defined as “diffuse, symmetric, generalized muscle weakness detected by physical examination and meeting specific strength-related criteria, that develops after the onset of critical illness without other identifiable cause [2].

The pathophysiology of ICU-AW blames it on an inflammatory response, bioenergetic dysfunction, altered protein balance, neuronal axon degeneration, changes in muscle histology and muscle wasting. AW seems to be triggered by the critical condition and its severity is independent of the underlying primary condition. The rhythm of muscular mass loss due to bedrest of the critically ill is approximately 2% per day, a rate different between muscles and dependent upon the measurements taken [3].

A general term to comprise the syndrome that describes the clinical signs of suffering survivors of a lengthy admission in the ICU was coined as PICS (post-intensive care syndrome). PICS refers to a new or worsening disorder, be it physical (muscular weakness, diminished autonomy to cope with daily living), PTSD (posttraumatic stress disorder), depression or other neurocognitive disorder impeding the quality of life and being a significant financial burden for both individuals and the society as a whole [4]. It was established that about 22% of former critically ill patients develop PTSD while 28% will be taunted by depression (Davydow cited by 5). Long-term patient outcomes may include pulmonary, neuromuscular, psychiatric and cognitive impairments as well as alteration of the physical function. PA (physical activity) was suspected to have a positive impact on delirium outcomes in intensive care unit patients. Since delirium impacts 80% of MV patients, there were expectations for PA to positively impact delirium outcomes. Immobility and functional decline are considered as risk factors for delirium. In non-critical patients, PA seems to provide neuroprotective effects by increasing neurotransmitter and anti-inflammatory mediator release and to facilitate synaptic transmission. It also increases cerebral blood flow in older adults and oxygen extraction efficiency, improving cognition. Therefore, Jarman et al. performed a systematic review and meta-analysis to investigate the impact of PA interventions on delirium outcomes in ICU patients. Unfortunately, they found only low-quality evidence in favor of greater-intensity PA. They concluded that there was insufficient evidence to recommend PA as a stand-alone intervention to reduce delirium in the ICUs [5].

While pulmonary outcomes appear as impairment in spirometry, lung volume and diffusion capacity, the incriminated risk factors are the duration of mechanical ventilation and the diffusion capacity. Even if the pulmonary impairment is generally mild, it can persist for over five years.

The ICU-acquired weakness includes polyneuropathy and myopathy and blames the hyperglycemia, the SIRS, sepsis and MODS (multiple system organ dysfunction syndrome). Polyneuropathy can extend to five years, far more than myopathy. Disuse atrophy is attributable to immobility/bed rest. The impairment of physical function is described as disuse atrophy, an impairment in activity of daily living (ADL/IADL) and in 6-minutes walking distance. Systemic corticosteroids use, ICU-acquired illness, age, slow-resolution of lung injury and preexisting IADL impartment are selected risk factors. It is expected for ADL to improve within months, but the signs may persist for one year, while IADL is to disappear in two years. Long-term impairment for 6-min walk distance is to be expected.

Depression attributable to traumatic/delusional memories of ICU, sedation, psychiatric symptoms at discharge, and impairment of physical function might decrease over the first year. PTSD is to improve a little over the first year and is due to sedation, agitation, physical restraints and traumatic/delusional memories. Anxiety may persist for the first year and identifies as risk factors the following: unemployment, duration of mechanical ventilation, as well as overall risk factors, such as female gender, younger age, less education, pre-ICU psychiatric symptoms and personality. The cognitive function is affected by impairment in memory, alteration of the executive function, mental processing speed and visio-spatial ability. It blames for the occurrence of lower pre-ICU intelligence, ICU delirium, sedation, hypoxia and glucose dysregulation. Although it might significantly improve during the first year, residual deficits may last up to 6 years.

There is a toll on families as well, and they are but psychiatric, such as depression, PTSD, anxiety and complicated grief. When it comes to depression, among identical risk factors with the critically ill, distance to the hospital and restricted visiting emerge.

For PTSD, unsatisfactory communication along with dissatisfaction with a caring, passive preference for decision-making and a mismatch between involvement in decision-making and preferences contribute to the persistence of PTSD for four years or more after death or discharge.

Complicated grief is deepened by the knowledge gap of the patient’s wishes, while when it comes for children, paternal stress after discharge is associated with child stress and may persist even past childhood.

To the complexity of the postcritically ill syndrome, we can add the sequelae of critical illness: multidimensional functional disability (prolonged MV, compromised ambulation, pharyngeal muscle weakness, dysphagia, increased risk of aspiration, reduced health-related quality of life, a nutritional compromise leading to compromise physical and neurocognitive recovery [6]. Entrapment neuropathy manifests as foot or wrist drop that compromises rehabilitation and recovery, or frailty. Mood disorders, pressure injuries that contribute to increased post-ICU mortality, oral complications (gingivitis, dental caries, tooth injury or loss, need for longer dental follow-up), endocrinopathies (thyroid gland, adrenal function derangements, disruptive endocrine homeostasis and sexual function), changes in appearance (frozen joints, alopecia, scarring, disfigurement, complicated social reintegration), taste changes, hearing or vision changes, procedure-related trauma (rectal, urethral injury, vocal cord dysfunction, tracheal stenosis) and chronic renal dysfunction sometimes needing RRT (renal replacement therapy increased health care use and 1-year mortality [6].

The SCCM (Society of Critical Care Medicine) recommends discharge to subacute rehabilitation facilities once the acute medical issues are resolved, or to long-term acute care hospitals when greater medical specialization is required [7].

As long as life expectancy improves in Europe and ICU lengths of stay also in order to achieve survival, since predominantly medical admissions consume over 50% of yearly ICU treatment days, and as countries over Europe further in debt, as human resource to care for the critically ill and to take over after discharge is scarcer, post ICU syndrome becomes more and more prominent [7, 8].

Thus, the solution for the survivors of an ICU long stay appears to be rehabilitation in a specialized unit. The USA took the initiative since the early eighties by opening the LTACHs (long-term acute care hospitals) dedicated to ICU survivors suffering from a large spectrum of problems, such as weaning from prolonged mechanical ventilation, and nonsurgical complicated wound care (decubitus). The requirements of LTACHs imply not only compliance with the legal requirements of hospitals delivering acute care, but also multidisciplinary physician-led teams to supervise and coordinate individual complex patient programs that take over 25 days [9].

Articles from Europe, Australia and New Zealand, Africa and Asia are increasingly dedicated to rehabilitation of the ICU survivors. Thus, Herridge et al. were able to identify acronyms relevant for studies on the outcome of the critically ill: ICAP, ALTOS, FROG-ICU, RECOVER, THRIVE, My ICU care and ICU steps to name a few. They concomitantly questioned the ethics of indefinite trials of MV or ECMO support [6].

In addition, Reid et al. identified important reporting deficiencies in ICU delivered PR interventions that limit clinical implementation and future trial development [10].

3. Best practices identified, validated or confirmed

We will try to highlight the best practices identified as being associated with patient satisfaction and also with caregiver fulfillment as a patient. Seo and al tried to assess the functional recovery and promoted the AM-PAC score (Activity Measure Post-Acute Care) [11]. They recognized the post-intensive care syndrome as an obstacle for full recovery, which if ever happening, will do so in no less than three years and came up with a check list to qualify for rehabilitation starting the 3rd day after admission to the SICU (Surgical Intensive Care Unit). The check list comprises: no more than 2 vasopressors, no recent shock event (<4 hours), a mean BP ≥60 mmHg, heart rate ≤ 120 bpm, respiratory rate ≤ 24/min, axillary temperature ≤ 38°C, no dysrhythmia, RASS -2 to +2, FiO2 ≤ 0.5 and a PEEP ≤10 mmHg [11].

They recommended a rehabilitation plan comprising five steps to be performed 20 to 30 minutes on week days. The first step would be PROM (Passive Range of Motion) and Postural change. Then follows the start of active rehabilitation, The AROM (Active Range of Motion), with the head elevation at ≥60°. Upper and lower extremity exercises follow, then a sit to stand attempt followed by marching on the spot. As we can see, the intensity of the effort gradually increases, as the complexity of the movements. Seo’s article was preceded by Conradie et al. who in 2017 published their adapted early mobility readiness protocol, very similar to Seo’s check-list [12]. They included the PaO₂/FiO₂ ratio of ≥250, SpO₂ ≥ 90% and all the aforementioned hemodynamic parameters with overlapping values. They concluded that active rehabilitation in critically ill surgical patients was feasible and safe regardless of age provided the patients’ safety was checked before. Standing activity in the ICU was not routine postoperative care [11].

Vollenweider R et al. studied the sedated and ventilated ICU patients and concluded that passive early motion reduced the nitrosative stress, although there was no clear effect on cytokines. They advanced an early adapted mobility readiness protocol hoping to provide the healthcare professionals with an interim tool to identify the patients who would tolerate a therapeutic upright position. They aimed at incorporating the upright standing position into standard nursing care, which would be a huge step toward improving recovery [13]. Lang JK et al. performed a systematic review of the published clinical practice guidelines for early mobilization (EM) in the ICU and they found that there was agreement on the principle of implementing EM [14].

Verceles et al. ran a study on prolonged MV critically ill patients suffering of AW, comparing and measuring the outcome of the patients submitted to either UC (usual care) with those who underwent an additional progressive multimodal rehabilitation program (MRP). They found that the addition of an MRP improved strength, physical function and mobility and was associated with greater weaning success and discharge home [15].

Beach et al. used motion sensors to measure PA of the critically ill ventilated for more than 48 hours and expected to stay in the ICU for at least 5 days. They also measured energy expenditure. They found that PA levels during the first 5 days of admission in the ICU when measured using METs were low. Sedation was the main barrier reported by physiotherapists. Motion sensors are safe, but used early in the ICU have limited clinical utility since sepsis impacts on metabolic rate. Since the correlation of PA against ICU mobility scale was strong, motion sensors promise to be best exploited to monitor activity levels in interventional studies [16].

Lai et al. had previously demonstrated that twice daily EM sessions reduced days of MV of medical critically ill patients when introduced within the first 3 days of MV, by almost 3 days (from 7.5 to 4.7 days) and also diminishes the risk of prolonged MV (≥7 days). However, the differences did not reach statistical significance [17].

A recent study concluded that early exercise training using a bedside cycle ergometer in critically ill ICU survivors who received MV enhanced the recovery of gastrointestinal function and improved the patients’ nutrition status at hospital discharge [18].

When it comes to thoroughly assessing the methodology used in the studies dealing with EM of MV patients, a systematic review included in the Cochrane database concluded that the evidence for the effectiveness of EM on measure of physical function and performance is inconsistent and uncertain due to its low quality [19]. The same applies to adverse effects. There is hope that better-designed ongoing studies will clarify the issue of EM. This harsh conclusion emerged from the sample sizes (judged too small), clearly reported interventions and control conditions, but also the blinded outcome assessment that usually lacked. There is an additional need for standardization of outcome measures and to disentangle early intervention from the intensity of intervention [19].

According to this trend of refining research, Collet et al. initiated a study including relevant articles comprised in the electronic databases for a decade (2012–2022). They will assess the functional and cognitive rehabilitation interventions during admission [20]. In depth knowledge is unlikely to benefit, but current understanding is expected to be uplifted.

Results of PR (physical rehabilitation) studies are tricky to compare since CG (comparator groups) are different, Still, as O’Grady and all showed, the most common type of CG is usual care [21]. There is a remarkable heterogeneity in planned activities and CERT (Consensus on Exercise Reporting Template; proportion of reported items/total applicable) reporting deficiencies [21].

In line with this trend of thoroughness, Connolly et al. described the PRACTICE (physical rehabilitation core outcomes in critical illness), a protocol for the development of a core outcome set) [22].

At the end of the day, even if protocols to care for the MV patients are proposed and used, there are no validated techniques to prevent post-mechanical ventilation injuries and sequels.

As for those who require or look forward to apply an already established protocol, Raurell-Torreda et al. publish an early mobilization algorithm for the critical patient. There is an algorithm of decision-making, but also IMS (ICU Mobility Scale) objective according to safety criteria [23]. Garcia-Perez-de-Sevilla also investigated the effectiveness of physical exercise and neuromuscular electrical stimulation interventions for preventing and treating ICU-acquired weakness and concluded that both methods should be used to prevent significant muscle loss. If patients can cooperate, they recommend to prioritize physical exercise against neuromuscular electrical stimulation, as it is superior for improving functionality [24].

4. Controversies

Controversies were almost completely pinned by Laghi [25].

There is no doubt that rest is paramount for recovery. Potential benefits of increased bedrest in ill humans are already well known: conservation of metabolic resources to be used for healing and recovery; reduce oxygen consumption by muscles and divert oxygen delivery toward injured tissues and organs in need; reduce requirements for ventilation and the risk of VILI (ventilation induced lung injury); reduce requirements for high FiO2 and the risk of oxygen toxicity; improve blood flow to the central nervous system; reduce harmful falls and the stress to the heart; prevent ischemia and dysrhythmias; avoid pain from additional injury and to injured body parts [26]. Despite these benefits, when prolonged over the usual 6–9 hours of sleep, bedrest is associated with no trivial complications: skeleton muscle atrophy and weakness, joint contractures, thromboembolic disease, insulin resistance, microvascular dysfunction, insulin resistance, systemic inflammation, atelectasis and pressure ulcers [26]. Nondamaging exercise is a major stimulus for IL-6 release while IL-1 and TNF-α concentrations do not substantially increase with exercise. IL-6 is also a strong inhibitor of TNF-α and IL-1. Moreover, exercise induced IL-6 release from muscles is associated with elevated concentrations in plasma of the IL-IRA and IL-10, both anti-inflammatory mediators. Regulated exercise decreases C-reactive protein levels also. Thus, atherogenesis might be prevented by decreasing vascular inflammation and insulin-sensitivity is increased. Prolonged bedrest opposed, annulled the benefits of muscle exercise. Overall, the prevalence of ICU-AW is 48% [3].

Knowing that critically ill patients can lose over 15% of their muscle mass within one week, one can expect long-term detrimental effects [3]. The dominant method to assess muscle waste is ultrasound, followed by CT scans.

The rationale for rehabilitation in the ICU is not always crystal clear. Questioning the clinicians as to the shortcomings of implementing rehabilitation exercises in the ICU, Nickels et al. found out that it was unlikely attributable to a lack of perceived importance by nursing, medical or physiotherapy clinicians, the most likely to influence rehabilitation practices in the ICU [27].

As of today, several controversies emerge and seem to be there to stay at least for a while.

Rehabilitation in the ICU is different in medical compared to surgical ICUs. Mobility is sometimes easier to achieve in surgical patients who became critically ill due to their surgery need. Once solved, their recovery is accelerated by early mobilization. The validation of selection criteria to identify the long-stay ICU patients susceptible to best benefit from an ICU rehabilitation facility should be addressed in further studies [9].

4.1 Different approaches to the same issue

Different conclusions or outcomes, different types of research articles, various experiences, different patients, different spatial coordinates and socio-economic issues account for the variability of the outcome in terms of duration of complete recovery or length of stay. As for those for whom the ICU is one bridge too far, gentle and humane care is advanced and should be provided [9].

Lime in 2014, Patel et al. completed a secondary analysis on all patients (N = 104) enrolled in an RCT of early occupational and physical therapy vs. conventional therapy, which evaluated the endpoint of functional independence. Every single patient benefited from ITT (intensive insulin therapy) and blinded muscular strength testing on hospital discharge to assess the incidence of ICU – AW (clinically apparent weakness). Logistic regression analysis showed that early mobilization and increasing insulin dose prevented the incidence of ICU-AW, independent on the risk factors. Still, insulin may be associated with reduced ICU-AW, but its safety profile cautions against using it for preventive reasons. Further on, the dual effect of early mobilization in reducing relevant ICU-AW and promoting euglycemia suggested its potential usefulness as an alternative to ITT [28].

In an attempt to understand the discordant results of ICU-based PR (physical rehabilitation), O’Grady et al. found that there was heterogeneity and underreporting of CG (comparator group), which perhaps contributed to discordant results. Not uncommon in rehabilitation research, these findings suggest a common barrier. For instance, fidelity, means the PR received relative to the planned one. The author favors the use of RTSS (Rehabilitation Treatment Specification System), which describes rehabilitation treatments according to their targets, ingredients and mechanisms of action [21].

Anchored in modernity, Fuest et al. used AI (artificial intelligence) in an attempt to characterize the optimal individual dosage (frequency and level of duration) of EM (early mobilization). AI was able to divide a heterogenous critical care cohort into 4 clusters very different in terms of clinical characteristics and mobilization parameters. The different mobilization strategies according to the cluster supported the likelihood of being discharged home, thus giving room to an “individualized and resource-optimized mobilization approach” [29].

There are also issues as to the dose of PR administered. It appears that indeed, mechanically ventilated patients subject to usual care develop less adverse effects during PR compared to those critically ill MV patients submitted to an increase in early active mobilization. The study comes from the TEAM study investigators and the ANZICS Clinical Trials Group [30]. One year earlier though, Paton et al. stated that mobilization during critical care provided at higher levels, but not increasing the number of active mobilization sessions improved health status at 6 months [31]. The dosage of mobilization was measured by ICMS (Intensive Care Mobility Scale).

5. The road ahead

1. ICU rehabilitation future – preventing ICU-related complications, the contribution of telemedicine and AI (algorhythms and clusters, AI to enhance our thinking or to merely increase the feeling of doing something the righteous way); low-cost physiotherapy strategies (balloon blowing exercise during pandemics. Tailored ICU rehabilitation programs are needed in order to humanize the approach of the post-ICU survivors [9].

2. Potential for development

3. Rehab for both patients, families and caregivers

Among the recommendations to improve patient and family-centered outcomes after critical illness, we enlist: provide broad education on ICU outcomes and the continuum of critical care construct; ensure accountability and reporting of multidimensional outcomes at one year; include ICU outcomes as part of informed consent, perform trials of limited treatment, engage families in week-end goals of care discussions; prioritize basic and translational science inquiry into multisystem tissue injury and repair, risk stratification, role of nutrition and rehabilitation, and determination of outcome trajectories; integrate longitudinal, granular data on ICU outcomes into administrative data sets as the ongoing standard for patient-and family-centered data collection, foster local, national and international programs focused on ICU care continuum and advocate for permanent funding as a timely and urgent public health priority; ensure optimal, consistent and timely communication by the multidisciplinary team with family members; provide respectful and compassionate care for the patient and family and encourage their involvement at bedside and on a mandatory basis in end-of life decisions [6].

A metanalysis and systematic review on physical rehabilitation in the ICU concluded that it improved physical function and reduced ICU and hospital LOS (length of stay), although it failed to impact other outcomes [32]. However, PR (physical rehabilitation) had no impact on muscle strength, duration of MV, mortality and health-related quality of life, while rehabilitation delivered for less than five days per week was less effective than higher dosages [25]. Driven by the results of Wang’s research, Laghi advanced the hypothesis that peripheral muscle weakness in the ICU was a marker of disease severity rather than the proximate mechanism contributing to poor clinical outcomes. Moreover, it was already shown that there was a limited association between the diaphragm dysfunction and the limb muscle weakness in mechanically ventilated patients [25]. Finally, it appears that PR and including functional exercises delivered 5 days per week to the critically ill is worth the effort.

Swallowing function in the ICU is often severely impaired, mainly to the intubated patients, but not confined to them. A new entry in the ICU is the speech-language pathologist (SLP) who additionally provides expertise in cognitive communication and swallowing functions during and after MV, endotracheal tube in place or not, to say nothing of tracheostomy. SLPs role was increasingly growing since the COVID-2 pandemic, so the expertise they provided was highly appreciated [33].

It appears that occupational therapists as well became sensitive to critically ill patients. Thus, a study by Costigan et al. established that “there could be opportunities for occupational therapists to expand their role and spearhead original research investigating an enriched breath of ICU interventions” [34].

There are barriers blocking the recovery of the patients surviving an ICU stay, such as the regulatory requirements for acute inpatient rehabilitation, or funding-related issues due mainly to limited or no-insurance coverage. Research gaps and sources do not really help, but they have to be overcome by a joint effort of clinicians and researchers. Nurses also identified barriers to implementing protocols of rehabilitation, and they included staffing levels, lack of resources, poor care coordination, concerns about personal and team safety, lack of knowledge or training, invasive lines and medical instability, fear of dislodgement, neurological limitations and sedation, low priority, presence of endotracheal tubes, poor communication such as contradictory information which is a definite source of disbelief and loss of confidence, inadequate equipment, increased workload, fatigue, self-injury and time [6, 35].

According to Herridge, the ICU community can and should define our next priorities as mitigation of suffering and the sense of futility in the ICU and disability after discharge [6].

The ideal setting for survivors would be the comprehensive multidisciplinary outpatient ICU-follow-up clinics [8].

6. Conclusion

Balancing the potential beneficial effects of bed rest against muscle exercise is a challenging task. The large variety in the design of interventions renders any evidence-based conclusion impossible. The positive impact on functionality is undeniable and physical therapists must be involved. Although technical difficulties and questions remain, the pertinence of tailored rehabilitation regimens is not an issue. A multidisciplinary approach organized in outpatient post-ICU clinics with a broad referral network of specialists could be an answer for all ICU survivors, not only for those issued from the last pandemic.