Critical illness neuropathy (CIN), critical illness polyneuropathy (CIP) and myopathy (CIM) are conditions which coexist frequently and end up combined into CIPM or CIPNM. These definitions, overlapped significantly in thier clinical characteristics and ultimately required nerve conduction studies, EMG testing and tissue biopsies to confirm the diagnosis, which were very rarely resorted to by the fairly pragmatic crowd of ICU specialists. ICU-acquired weakness is a term which was devised to embrace all of these categories, which is based on clinical examination and therefore "can be applied more generously" to borrow a turn of prase from Schweickert & Hall (2007).

In summary:

  • ICU-acquired weakness is a clinical diagnosis of weakness in critically ill patients in whom there is no plausible etiology other than critical illness.
  • It is formally defined as a sum score of less than 48 on the MRC muscle power scale 
  • Subclassficiations include:
    • Critical illness polyneuropathy (CIP) - confirmed by nerve conduction studies
    • Critical illness myopathy (CIM) - confirmed by EMG
    • Combination of both (CIPM)

The CICM examiners still referred specifically to "Critical Illness Polymyoneuropathy (CIP)" in Question 10 from the first paper of 2013. It also appeared as one of the differentials (Question 25 from the first paper of 2012), and  it inevitably ends up in the hot cases. Locally, an approach to the ICU patient with generalised weakness digresses briefly on to CIP. A LITFL article on critical illness polyneuropathy offers a good revision resource. Much of this summary has been strained out of the excellent second part of the "Neurologic Complications of Critical Illness" series by Sanap and Worthley; the reason for using this as a primary source is the great likelihood that Worthley wrote a massive number of CICM fellowship questions. Hermans & Van den Berghe published a more recent review in 2015.

Definition and classification of ICU-acquired weakness

It would appear that virtually every author who has published on this subject had decided to create their own name for the same cluster of clinical findings. Stevens et al (2009) is an excellent discussion of this lawless swamp. They discovered eighteen definitions just in the 1990-2009 timeframe ("intensive care unit-acquired neuromyopathy", "ICU-acquired paresis", "polyneuropathy in critically ill patients", "acute necrotising myopathy of intensive care", and so on). Stevens et al proposed their own definition to bring some order into this environment:

"ICU-acquired weakness ... is clinically detected weakness in critically ill patients in whom there is no plausible etiology other than critical illness."

Within this clinical definition, patients who actually do undergo formal EMG or nerve conduction testing may be further subclassified as CIP, CIM, or CINM.

How weak does one have to be, and what defines "ICU-acquired"? Well. Manual muscle testing using the Medical Research Council (MRC) score is probably the best-known technique. Ciesla et al (2011) explore in detail; for this short summary it will suffice to say that it requires testing each of the muscle groups of the extremities and generating a six-point ordinal score. This scoring system is usually referred to as the MRC-SS (SS stands for "summed score"), and was developed by Kleyweg et al (1991) to track th recvery of patients with Guillain‐Barré  syndrome. To simplify revision, the testing scale is reproduced here:

Grade Manual Muscle Test
5 Movement against gravity plus full resistance
4 Movement against gravity plus some resistance
3 Completes the available test range of motion against gravity, but tolerates no resistance
2 The patient completes full or partial range of motion with gravity eliminated
1 Slight contractility without any movement
0 No evidence of contractility (complete paralysis)

Six muscle groups are tested bilaterally (shoulder abduction, elbow extension, wrist extension, hip flexion, knee extension, ankle dorsiflexion).  The total score can therefore range from 0 (complete paralysis) to 60 (fully preserved muscle power).

By using data collected prospectively from critically ill patients, a cutoff of <48 points (i.e. a global 4/5 weakness) was found to be the most effective threshold for identifying those who are weak enough to suffer complications. The most influential study which is credited with this cutoff is probably De Jonghe et al (2007), who found that patients with a median MRC sum score of 48 or above were intubated for less than 7 days. Those were mainly septic shock patients (50%) with ARDS (28% of them) who ended up full of steroids (63%) and neuromuscular junction blockers (39%). 

Clearly, the manual muscle testing has limitations. ICU patients are often delirious and uncooperative, with variable communication problems, often on sedation, and so of course their performance in this muscle testing will vary from hour to hour and day to day, even when interobserver agreement is good. Connolly et al (2013) agreed that "interobserver agreement for the diagnosis of ICU-AW is a consequence of patient rather than clinician variability during testing". Of their cohort of weakned patients, MRC scores of over 48 were strongly predictive of an ICU stay of less than 2 weeks, whereas scores of under 48 were nor partricularly predictive of a longer stay (i.e. patients who appeared weak on testing ended up recovering their strength relatively quickly).

Moreover, the scoring of the upper range of MRC scores has come under criticism for being too subjective and difficult to reproduce (as one clinician's "full resistance" might only be as good as another clinican's "some resistance"). Moreover, not all ICU patients will be patiently cooperative with the full testing process, and some may have missing or immobilised limbs which confuses the scale. Lastly, the MRC does not test respiratory muscle power, which is what the intensivist will be interested in from an extubation point of view.  Solutions involving various objective surrogates (have been developed, but so far have failed to achieve the same level of popularity as the MRC because of reliance on expensive equipment or lack of validation in large trials. For the sake of completeness, here is a short list of these objective tests:

Risk factors associated with ICU-acquired weakness

Yang et al (2018) performed a meta-analysis of independent risk factors for ICUAW, and they are well summarised in the "Risk factors" section of Hermans & Van den Berghe (2015).  One might be able to separate these arbitrarily into "modifiable" and "non-modifiable", for no reason other than to give the college examiners an impression of orderliness and organisation.

Modifiable risk factors

  • Prolonged critical illness 
  • Neuromuscular junction blockers
  • High dose corticosteroids 
  • High dose vasopressors
  • Immobility, prolonged bed rest
  • Hyperglycaemia
  • Use of aminoglycosides

Non-modificable risk factors

  • Female gender
  • Low baseline muscle mass
  • Premorbid malnutrition
  • Severe sepsis 
  • Multiorgan system failure 
  • Higher severity of illness (high APACHE and high SOFA scores in the first week)

After an ICU stay of 7-10 days, ICU acquired weakness was present in 24-55%

Clinical characteristics of CIPM:

  • Presents about 1 week into the critical illness
  • Sensation is preserved
  • Symmetrical deficits
  • Predominantly proximal weakness
  • Present reflexes, albeit diminished
  • Normal CSF findings
  • Cranial nerve function and autonomic nervous system function are usually preserved
  • CK may be raised, especially if myopathy plays the greatest role
  • Nerve conduction studies demonstrate normal conduction velocities, but decreased compound muscle action potentials (CMAPs)

Preventative measures to protect from CIPM

A recent Cochrane review has identified a few preventative measures:

  • Strict glucose control (though the protection comes at a cost of episodic hypoglycaemia)
  • Early mobility rehabilitation
  • Electrical muscle stimulation (EMS) may play a role, but this technique is so far in its infancy.

Common sense (personified by the LITFL authors) also recommends the following preventative strategies:

  • Adequate nutrition
  • Electrolyte replacement
  • Minimised use of steroids, sedation and NMJ blockade
  • Physiotherapy with limb mobilisation while still critically ill
  • Conscious effort to wean ventilation

References

Oh's Intensive Care manual:

Chapter   57   (pp. 617)  Neuromuscular  diseases  in  intensive  care by George  Skowronski  and  Manoj  K  Saxena

Worthley, L. I., and M. N. Sanap. "Neurologic complications of critical illness: part II. Polyneuropathies and myopathies." (2002): 133.

.Hermans, Greet, et al. "Interventions for preventing critical illness polyneuropathy and critical illness myopathy." Cochrane Database Syst Rev 1 (2014).

Trojaborg, Werner, Louis H. Weimer, and Arthur P. Hays. "Electrophysiologic studies in critical illness associated weakness: myopathy or neuropathy–a reappraisal." Clinical neurophysiology 112.9 (2001): 1586-1593.

Hermans, Greet, and Greet Van den Berghe. "Clinical review: intensive care unit acquired weakness." Critical care 19.1 (2015): 274.

Stevens, Robert D., et al. "A framework for diagnosing and classifying intensive care unit-acquired weakness." Critical care medicine 37.10 (2009): S299-S308.

Ciesla, Nancy, et al. "Manual muscle testing: a method of measuring extremity muscle strength applied to critically ill patients." JoVE (Journal of Visualized Experiments) 50 (2011): e2632.

De Jonghe, Bernard, et al. "Respiratory weakness is associated with limb weakness and delayed weaning in critical illness." Critical care medicine 35.9 (2007).

Connolly, Bronwen A., et al. "Clinical predictive value of manual muscle strength testing during critical illness: an observational cohort study." Critical Care 17.5 (2013): R229.

Nanas, S., et al. "Predisposing factors for critical illness polyneuromyopathy in a multidisciplinary intensive care unit." Acta Neurologica Scandinavica 118.3 (2008): 175-181.

Yang, Tao, et al. "Risk factors for intensive care unit‐acquired weakness: A systematic review and meta‐analysis." Acta Neurologica Scandinavica 138.2 (2018): 104-114.

Bednarik, Josef, et al. "Risk factors for critical illness polyneuromyopathy." Journal of neurology 252.3 (2005): 343-351.

Kleyweg, Ruud P., Frans GA Van Der Meché, and Paul IM Schmitz. "Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain‐Barre syndrome." Muscle & Nerve: Official Journal of the American Association of Electrodiagnostic Medicine 14.11 (1991): 1103-1109.