Understanding ICU-Acquired Neuromuscular Dysfunction: Triggers, Risk Factors, and Treatments

Some form of neuromuscular dysfunction occurs in as many as 80% of critically ill patients admitted to the intensive care unit (ICU), although the number of patients affected varies depending on specific risk factors.¹ Following a critical illness, patients admitted to the ICU may be vulnerable to neuromuscular complications, which can lead to long-term disability or to a general deterioration in physical and cognitive functioning. 

Of these complications, one of the most common is ICU-acquired weakness (ICUAW). ICUAW is usually a consequence of critical illness myopathy (CIM) or critical illness polyneuropathy (CIP), or a combination of both. Because they often coexist, CIP and CIM can be difficult to differentiate and are therefore referred to collectively as critical illness neuromuscular abnormalities or CIM and/or neuropathy. Previous studies have shown that the risk for either CIP or CIM occurring in patients in the ICU ranges between 47% and 90%.²

According to Rajshekher Garikapati, MD, a neurologist at University Hospital Sharjah in the United Arab Emirates, “Up to 62% of patients who experience failure to wean from the ventilator have some form of neuromuscular weakness. Isolated CIP is possibly rare and somewhat controversial, but CIM and CIP [are] reported in 25% to 83% of patients, depending on the type of critical illness they have.”

CIP and CIM: Triggers and Risk Factors

Based on research by Sarah Jolley, MD, MSc, and colleagues, acute weakness appears to be common in patients who have received prolonged ventilation.³

ICUAW stems from different pathophysiologic mechanisms, which manifest differently in every patient. This makes it challenging to diagnose and differentiate between CIM and CIP. “CIM is represented more by proximal weakness than distal weakness. It is characterized by atrophy and sensory preservation, depending on the duration of the critical illness. Meanwhile, CIP is more distal than proximal weakness and is characterized by limited atrophy and sensory changes,” Dr Garikapati said. He emphasized that it is imperative to consider other medical conditions like cardiac, pulmonary, or endocrine disorders before diagnosing CIP or CIM. Contrary to Guillain-Barré syndrome, myasthenia gravis, Lambert-Eaton myasthenic syndrome, and other neuromuscular disorders, the bulbar muscles usually remain unaffected in CIP and CIM.

Early studies defined CIP as a symmetric weakness affecting the proximal limb muscles through denervation and denervation atrophy. In some cases, CIP could have an impact on the respiratory muscles and delay weaning from mechanical ventilation. Typically, electrophysiologic and muscle-biopsy studies can lend clarity, but such studies are technically difficult to conduct on critically ill patients. The common indicators or risk factors associated with ICUAW include prolonged mechanical ventilation, prolonged sepsis or inflammation, treatment that involves glucocorticoids or neuromuscular-blocking agents, or uncontrolled hyperglycemia. Malnutrition and preexisting sarcopenia may also contribute significantly.⁴

Dr Nickson states that the onset of CIP is usually within a week of the critical illness. Sensations tend to be preserved, in that deficits may be present with axonopathy, but factors such as edema or patient coma make this difficult to evaluate. In the long run, most patients can recover and are able to walk, although a small number are left with mild disability. Severe paraplegia, quadriparesis, or quadriplegia may develop in up to 30%.⁵ Other frequently reported disabilities include distal sensory loss, muscle atrophy, and decreased reflexes.²

Recovery and treatment are dependent on the condition. In one study, one-third of those with severe acquired brain injury in the ICU who were admitted to a rehabilitative environment had ICUAW.⁶ Following rehabilitation, functional recovery improved but these patients had poorer outcomes and longer rehabilitation treatment than those with severe acquired brain injury with no ICUAW.

Mitigating Outcomes

Clinical evidence on mitigating CIP and CIM is surprisingly limited. Earlier studies showcased potential linkages, but these were not necessarily replicated. For example, a study on critically ill patients that targeted normoglycemia (glucose concentration of 80-110 mg/dL) found an association with lowered critical illness neuromuscular abnormalities or CIM and/or neuropathy and a reduced need for mechanical ventilation.⁷ More recent therapies include minimizing sedation and mobilizing patients early. In cases where mobilization is not possible, passive exercises can strengthen recovery.⁵

A recent recommendation by ICU specialists is to consider factors such as functionality, age, and premorbid ICU conditions when assessing ICUAW. Equally critical to consider are the effects of different ICUAW types, the reason for ICU admission, the role each disorder plays in disability, and rehabilitation interventions.⁸ With increased research into mitigating ICU weaknesses, the focus on a multidisciplinary approach is growing. For instance, a neurologist’s expertise can be applied to analyzing questionable CIP and CIM electrophysiologic pictures in greater detail, thereby not limiting ICUAW as a one-off neurologic anomaly in the ICU.⁶

ICU experts also agree that following ICU discharge, physical therapy interventions must include functional and strengthening exercises as well as endurance training and education on nutrition.⁹ According to Dr Jolley, “Adjustment for baseline function may help specialists to understand the disease trajectories for ICUAW. Novel diagnostic methods such as single nerve conduction study and muscle ultrasound may provide a minimally invasive means for early recognition of disease. Studies are needed to explore interventions targeted at patient participation and stage of disease rather than being applied uniformly across the spectrum.”³ Other critical determining factors include evaluating a patient’s comprehensive history and undertaking thorough neurologic assessments.²

Holistic Pathways

The diagnosis and treatment of ICUAW, and particularly of CIM and CIP, is still a work in progress. ICUAW syndromes manifest themselves in a range of ways among patients — as a spectrum of disease rather than in specific form. Therefore, it is challenging to pinpoint the exact cause and resolve the problem. Medical testing modalities are limited in the critical care environment. As Dr Garikapati highlights, “In the context of nerve conduction studies, the performance of electrodiagnostic studies in the ICU setting poses significant challenges. These include interference from other electrical devices, inaccessibility of a specific body part, temperature changes in limbs, limb swelling due to edema secondary to malnutrition or other conditions, and the common inability of a critically ill patient to cooperate.” These limitations further compound the challenge of achieving an early identification of CIP and CIM. As such, a holistic and multidisciplinary approach is necessary.

References

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2. Khoiny AS, Behrouz R. Critical Illness Polyneuropathy and Critical Illness Myopathy. [online] Pract Neurol (Fort Wash Pa). http://practicalneurology.com/2011/06/critical-illness-polyneuropathy-and-critical-illness-myopathy/. May/June 2011. Accessed May 10, 2018.
3. Jolley SE, Bunnell AE, Hough CL. ICU-acquired weakness. Chest. 2016;150(5):1129-1140.
4. Finfer S, Vincent J-L. ICU-acquired weakness and recovery from critical illness. N Engl J Med. www.nejm.org/doi/story/10.1056/feature.2014.04.15.26. April 2014. Accessed May 11, 2018.
5. Nickson C. ICU acquired weakness (ICUAW). Life in the Fast Lane: Critical Care Compendium. https://lifeinthefastlane.com/ccc/icu-acquired-weakness. Updated September 10, 2017. Accessed May 11, 2018.
6. Intiso D, Di Rienzo F, Fontana A, Tolfa M, Bartolo M, Copetti M. Functional outcome of critical illness polyneuropathy in patients affected by severe brain injury. Eur J Phys Rehabil Med. 2017;53(6):910-919.
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8. Latronico N, Herridge M, Hopkins RO, et al. The ICM research agenda on intensive care unit-acquired weakness. Intensive Care Med. 2017;43(9):1270-1281.
9. Major ME, Kwakman R, Kho ME, et al. Surviving critical illness: what is next? An expert consensus statement on physical rehabilitation after hospital discharge. Crit Care. 2016;20(1):354.