Critical Care Medicine

Weakness, Acquired Muscle Weakness and Peripheral Nerve Disease in the ICU, critical illness myopathy, critical ilness polyneuropathy, prolonged neuromuscular blockade

Acquired Muscle Weakness and Peripheral Nerve Disease in the ICU

Also known as: Critical illness myopathy (CIM), critical ilness polyneuropathy (CIP), prolonged neuromuscular blockade (PNMB)

Related conditions: Prolonged neuromuscular blockade, Guillain-Barré syndrome (GBS), myasthenia gravis (MG), botulism, Lambert-Eaton myasthenic syndrome, porphyria, amyotrophic lateral sclerosis (ALS), tick paralysis, acute flaccid paralysis

1. Description of the problem

What every clinician needs to know

It has become apparent in recent years that there are a number of long-term sequelae from critical care. Of these complications, severe weakness is one of the most significant. The generalized weakness often seen in patients who have survived critical illness can prevent participation in rehabilitation, prolong time on the ventilator and prolong hospitalization, and can lead to secondary complications of pressure ulcers and prolonged periods of dependency.

Clinical features

It is useful to distinguish between neuromuscular disease that is present prior to ICU admission and neuromuscular disorders that develop during the course of ICU care. While many neuromuscular diseases can result in an ICU admission, there are a limited number of disorders that produce acquired weakness during the course of ICU care. This section will focus on the ICU-acquired weknesses and their causes. For information about neuromuscular disease that can result in ICU admissions and/or complicate ICU care, see the section "Neuromuscular Disorders in the ICU."

Key clinical features of acquired weakness are persistent flaccid generalized weakness that is symmetric and equally severe both proximally and distally, with occasional distal greater than proximal distribution. These features result from the location of the injury in the muscle, nerve or neuromuscular junction.

Key management points

The two primary conditions that underlie the weakness are dysfunction in muscles, peripheral nerves or their synapse. Dysfunction of the muscle is called critical illness myopathy (CIM) and dysfunction of the nerve is referred to as critical illness polyneuropathy (CIP). A third possible condition is prolonged neuromuscular blockade, which is persistent dysfunction at the neuromuscular junction after discontinuation of neuromuscular blocking agents.

Although often discovered during the recovery phase of acute illness, it is imperative to exclude central causes for the weakness such as stroke and hemorrhage before making the diagnosis of CIM/CIP. Complete absence of reflexes is often a clue that a peripheral cause underlies the weakness. Likewise, asymmetry in the weakness, either left compared to right or upper limbs compared to lower, is suggestive of a central cause for the weakness.

Management and evaluation of ICU patients with weakness is detailed in the following segments and consist of optimizing nutritional status, and evaluation with imaging and electromyography and nerve conduction studies (EMG/NCS) when appropriate.

2. Emergency Management

By its very nature, critical illness-related weakness is non-emergent. This is because the condition does not lead to critical care but develops over the course of critical care. Once weakness is discovered it is imperative to exclude both pre-existing conditions and central causes for the weakness. Intracranial stroke or hemorrhage can result in weakness, as can spinal cord injury. A careful exam and detailed patient assessment is key in determining the need for and location of imaging (Figure 1). Once life-threatening central causes have been excluded, then further evaluation of the peripheral causes of weakness can be undertaken. Key differentiating clinical features are provided in the diagnosis segment below.

Figure 1.

Simple approach to the serial evaluation and management of acquired weakness in critically ill patients.

A suggested approach to the detection and management of weakness in the ICU is provided in Figure 1. Serial examination of ICU patients is an important factor in early detection of weakness and provides significant insight into the likely cause for the weakness.

3. Diagnosis

Diagnostic criteria

Although formal neurophysiologic criteria are provided here, in the majority of cases both CIP and CIM are present, making the formal distinction less important and less likely to achieve. Further, there is no change in long-term management, though severe axonal damage (i.e. predominant CIP) is less likely to improve completely or as quickly as predominant CIM. Figure 1 provides a framework for evaluation and diagnosis. Prolonged neuromuscular blocakde is also described here, but generally this is self-limited and resolves quickly over time.

Normal lab values

CIM clinical features

- Generalized symmetric flaccid weakness

- Loss of deep tendon reflexes

- Abnormal electromyography with voluntary contraction

- Abundant low-amplitude, short-duration, polyphasic units

- Early recruitment

- Biopsy of muscle shows fiber atrophy (type II), occasional necrosis, regeneration, and reduced adenosine

CIP clinical features

- Generalized symmetric flaccid weakness

- Loss of deep tendon reflexes

- Sensorineural axonopathy on formal electrophysiologic testing

- Decreased compound muscle action potential amplitude

- Decreased sensory nerve action potential amplitude

- Normal conduction velocities

- Electromyography shows fibrillation potentials and spontaneous activity.

Prolonged neuromuscular blockade (neuromuscular junction) dysfunction

- Generalized symmetric weakness

- Similar to CIP with reduced nerve-mediated compound muscle action potentials

- Generally rapidly improves over time

- Exact impact on neuromuscular studies will depend on the mechanism of the neuromuscular blocking agent.

How do I know this is what the patient has?

If risk factors for CIP/CIM are not apparent, assess risk for a central event or other cause for the weakness. Exclude pre-existing conditions as a source for weakness. EMG/NCS can be very helpful in confirming abnormalities of nerve and muscle function. In the absence of abnormalities in the EMG/NCS, imaging of the central axis should be performed.

Differential diagnosis

In setting of acute viral illness such as West Nile, acute flaccid paralysis is a consideration. If weakness is focal or asymmetric, or is accompanied by sensory abnormalities, then brain imaging is appropriate. If the weakness is asymmetric between upper and lower extremities, the cervical spine should also be imaged. Rhabdomyolysis and electrolyte imbalance should also be excluded through appropriate laboratory assessment.

Confirmatory tests

In general, EMG/NCS and CNS imaging are sufficient to make the diagnosis. In some cases of severe weakeness, muscle and/or nerve biopsy can be helpful in determining the presence of other contributing neuromuscular conditions. These cases should be assessed by neuromuscular subspecialists when available.

4. Specific Treatment

Unfortunately there is no specific treatment for CIM/CIP. Maintaining a high level of nutrition during the acute illness is important, and appropriate nutrition appears to be important for recovery. It is always advisable to avoid prolonged neuromuscular blockade and avoid coadministration of neuromuscular blocking agents and steroids. Cases of prolonged neuromuscular blockade are generally related to slow metabolism of the blocking agent and will eventually clear and improve with time.

5. Disease monitoring, follow-up and disposition

EMG/NCS can be prognostic and useful in following recovery. It can also help determine if other conditions may exist and are contributing to the clinical weakness observed. Importantly, once weakness is discovered, a careful exam must be performed to determine the pattern of weakness. As shown in Figure 1, if the weakness is asymmetric, particularly between upper and lower limbs, the cervical and thoracic spinal cord levels should be imaged in addition to the brain imaging.

If EMG/NCS results are normal, consider other causes for the weakness, particularly central lesions such as stroke and spinal cord lesions. MRI is the preferred modality, particularly for spinal cord evaluation.

Pathophysiology

The exact mechanism by which neuromuscular blocking agents and steroids contribute to disease is unknown. So, too, are the mechanisms underyling the dysfunction caused by sepsis and other infections. It is clear that immobility is a contributor as well, but alone it does not produce the myopathic changes seen on biopsy of CIM/CIP cases.

It has been suggested that alterations in the microcirculation that accompany SIRS and sepsis and contribute to other organ failure are likely to underlie the failure of the neuromuscular system as well. Failure in mitochondrial energy production in the setting of hypoxia related to microcirculatory failure is part of this proposed mechanism of injury (see Hermans et al., 2008 [PUBMED:19040777] and Bolton, 2005 [PUBMED:15825186] for additional details).

Epidemiology

EMG-based studies have shown that CIM/CIP is more common in ICU patients than clinically appreciated. Evidence for one or both is seen in muscle biopsy and EMG in about 70% of ICU patients; however, only half have appreciable weakness on exam. Patients with underlying inflammatory disease processes such as sepsis, SIRS and acute respiratory distress syndrome (ARDS) are at the highest risk for CIM/CIP. If multiorgan system failure is also present, the rate of CIP/CIM is essentially 100%.

There are clear linkages to the concurrent use of neuromuscular blocking agents and steroids in critically ill patients. Hyperglycemia also appears to be a risk factor, with aggressive insulin therapy leading to a reduced incidence of CIM/CIP. Patients who are not fed or do not tolerate feeds are at high risk for developing weakness from disuse and catabolic metabolism. Thus, while the exact mechanisms underlying the development of CIP/CIM are unclear, these risk factors point to deranged metabolic state, catabolic metabolism and systemic inflammation as important contributors.

Prognosis

Most make a good recovery, but a significant portion (20-30%) will have persistent deficits that are likely permanent. Survivors of sepsis and ARDS appear to be at slightly higher risk for long-term deficits. Most of the studies that report on outcomes of patients with ICU-acquired weakness suggest that even in patients with good recovery of overall function, most have persistent deficits out to 1 year post discharge or even longer. These data are consistent with the notion that both CIP and CIM are present in most cases.

What's the evidence?

Bolton, CF, Gilbert, JJ. "Polyneuropathy in critically ill patients". J Neurol Neurosur Psychiatry. vol. 47. 1984. pp. 1223-31.

Bolton, CF, Laverty, DA. "Critically ill polyneuropathy". J Neurol Neurosurg Psychiatry. vol. 49. 1986. pp. 563-73.

(These two studies are the original description of critical illness polymyopathy.)

Bolton, CG. "Neuromuscular manifestations of critical illness". Muscle Nerve. vol. 32. 2005. pp. 140-63.

(This is a solid review by the person who is credited with describing and characterizing the clinical condition of CIP/CIM. Very in-depth about possible mechanisms behind the condition.)

Hermans, G, De Jonghe, B. "Clinical review: Critical illness polyneuropathy and myopathy". Crit Care. vol. 12. 2008. pp. 238.

(Very nice review, detailing the clinical presentation, risk factors, possible mechanisms for development, and potential prevention and treatment options.)

Schweickert, WD, Hall, J. "ICU-acquired weakness". Chest. vol. 131. 2007. pp. 1541-9.

(Also a very nice review, detailing the clinical presentation, distinguishing features, risk factors, outcomes, and diagnostic approachs with algorithms.)
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