Critical Illness Polyneuropathy (CIP)

Original Editor - Matt Ross Top Contributors - Matt Ross, Karen Wilson and Adam Vallely Farrell

Definition

Critical Illness Polyneuropathy (CIP) is one of three classifications of Intensive care -unit acquired weakness (ICUAW), the others being Critical Illness Myopathy (CIM) and Critical Illness Neuromyopathy (CINM)[1]. ICUAW is defined as 'a clinically detected weakness in critically ill patients in whom there is no plausable aetiology other than critical illness' [2]

Pathological Process

The pathophysiology for CIP remains unclear and complex, with human studies highlighting axonal degeneration [3].It has been thought that the mechanism may involve:

  1. Microvascular alterations: Increase in E- Selectin expression, vasodilation, increased capillary permeability, extravasation and endoneural oedema which results in hypoxia.
  2. Metabolic alterations: Production of toxic factors such as cytokines, hyperglycaemia, hormone imbalance, hypoalbuminemia, amina acid deficiency and activation of proteolytic pathways.
  3. Electrical alterations: Ion channel dysfunction, cell depolarisation, inexcitability, altered calcium homeostasis and changes in excitation-contraction coupling.
  4. Bionenergetic failure: Anti-oxident depletion, an increase in reactive oxygen species, mitochrondial dysfunction and apoptosis.
Hermans et al (2008)
Zhou et al (2014)

The endoneural edema resulting from increased permeability may impair energy delivery to the axon followed by axonal death. Direct toxic effects and mitochondrial dysfunction evoked by hyperglycemia may contribute to this process. Animal experiments also identified channelopathy as a cause of rapidly occurring but reversible neuropathy[4].

Risk Factors
  • Sepsis
  • SIRS
  • Multi Organ Failure (MOF)
  • Female Gender
  • Duration of Organ Dysfunction
  • Duration of ICU Stay
  • Ionotropic Support
  • Renal Failure
  • Low Serum Albumin
  • Hyperglycemia
  • Neuromuscular Blockades
  • Corticosteroids

Clinical Presentation

Visser (2006) [5] reports that the clinical features of CIP typically include:

  • Muscle Weakness: Predominantly in the lower extremities. This should be suspected if there is reduced limb movement following a painful stimulus to the distal limb. Flaccid weakness can be observed symmetrically.
  • Absent Facial Weakness: Cranial nerves are rarely affected.
  • Muscle Wasting: Observed in one third of patients
  • Reduced Muscle Reflexes: Reflexes are usually present at the start of the disease, but decrease over time.
  • Difficulty in Weaning from Ventillator
  • Sensory Loss: Although difficult to assess with a sedated or intubated patient.
  • Impaired Consciousness: Suggested of an encephalopathy is also usually present


Diagnostic Procedures

Medical Research Council (MRC)
Hermans and Berghe (2015)

Also known as the Oxford Muscle Grading System, the MRC is a measurement of muscle strength ranging from 0 (no contraction at all) to 5 (normal). To assist with the diagnosis of CIP, bi-lateral testing of shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and dorsiflexion of the ankle will create a total score of 60[4]. 48/60 designates ICUAW or significant weakness, and an MRC score below 36/48 indicates severe weakness[6]

Electrophysiological testing

This includes both nerve conduction studies and electromyography examination, however these resources are limited at a number of ICU's. Typically, nerve conduction studies highlight a reduced compound muscle action potential (CMAP) and in some instances the sensory nerve action potentials (SNAPs) may be reduced. Nerve conduction velocity is usually normal or minimally reduced[7].

BIOMARKERS

Currently there are no validated biomarkers available, creatine kinase and plasma levels of neurofilaments (a marker of axonal injury) are elevated in those with ICUAW, however the former not being a particular reliable biomarker[8][9] as they are normal when muscle necrosis is absent or scattered which, with CIP, is commonly the case[10].

Biopsy

Although not commonly performed, CIP will demonstrate features of denervation and reinnervation with small muscle fibers, fiber-type grouping, and fiber group atrophy with widespread axonal degeneration of both motor and sensory nerves. Muscle biopsy can display thick filament loss which is commonly associated with CIM, with evidence of denervation and reinnervation changes and axonal degeneration associated with CIP[11].

ALGORITHM

Developed by Latronico and Gosselink (2015)[12], this algorithm has been designed to assist in the initial diagnosis of ICUAW:

Latronico and Gosselink (2015)

Outcome Measures

Muscle Strength Testing (MRC)

Management / Interventions

MEDICAL
Zhou et al (2014)
  1. Glycemic Control: Studies have shown that intensive insulin therapy for hyperglycemia lowered the risk of critical illness polyneuropathy and myopathy, and decreased time on ventilatory support, the duration of intensive care unit stay, and the 180-day mortality rate[3].
  2. Optimising Nutrition
  3. Treatment of Sepsis: It is likely that adequate and early treatment of sepsis will reduce the incidence of CIP. Treatment modalities to reduce this risk are centered around the use of semi- recumbent positioning, use of low tidal volume mechanical ventilation, and no or careful use of sedative or neuromuscular-blocking agents.
  4. Neuromuscular Blockades: Risk factors for prolonged neuromuscular blockade in patients in the ICU include hepatic or renal failure, hypermag- nesemia, metabolic acidosis and the concomitant use of various antibiotics, especially aminoglycosides and clindamycin[5].
PHYSICAL

Long periods of immobilisation are now being recognised as an important aspect to address when managing CIP performing rehabilitation early on is a key focus in the NICE guidelines (2009)[13]. Early mobilisation has shown to facilitate and improve long-term recovery[24,86,92] and functional independence of patients, and shorten the duration of ventilation and hospitalisation[14]. Treatment should be tailored to the clinical presentation of the patient and could include:

  • Passive range of movement to maintain muscle length and prevent contractures due to prolonged bed rest.
  • Active / active resisted exercises to improve strength and endurance.
  • Positioning in bed to facilitate improved lung function.
  • Sitting on edge of bed to facilitate trunk control / balance.
  • Sitting out in chair to improve lung function (either via pat slide, hoist, standing hoist or transfers).
  • Mobilising to improve lung function, cardiovascular fitness, muscle strength and promote independence.


evidence
  • Kayambu et al (2013)[15]: Systematic review of 10 RCT's and 5 reviews. Physical therapy resulted in significant benefits in improving quality of life, physical function, peripheral and respiratory muscle strength and decreased hospital and ICU length of stays.
  • Bahadur et al (2008): Those who participated in rehabilitation had decreased mortality rates and an increase in percentage of patients discharged from ICU.
  • Chiang et al (2006)[16]: Group who performed upper and lower limb exercises with functional activities report an increase score in their functional independence measure and their maximum inspiratory pressure.

Differential Diagnosis

Guillain-barre syndrome (GBS)

GBS is an autoimmune disease of the peripheral nervous system that is typically progressive and symmetric with ascending paralysis, sensory abnormalities and areflexia, with 30% of patients requiring mechanical support [17].

Never conduction tests highlights decreased velocity in GBS whereas normal conduction velocity and decreased action potentials. The stand out difference between CIP and GBS is that CIP is a part of critical illness that typically occurs during an intensive care stay, whereas GBS leads to an intensive care admission [3].

trauma

A spinal cord or head injury should be ruled should there be muscle weakness following a traumatic injury, as spinal shock can result in muscle weakness and areflexia [5]

neuromuscular blockades

Prolonged neuromuscular blockades can result in the development of acute quadriplegic myopathy, and can be identified by repetitive nerve stimulation. This can be reversed by giving cholinesterase inhibitors. Sensation and reflexes are usually spared [5]

CRITICAL ILLNESS MYOPATHY (CIM)

CIP and CIM usually co-exist during ICUAW[18], however there are some differentials highlighted in the table below:

Screen Shot 2018-06-13 at 12.58.32.png
Coincident illness

These include:

  • Eaton-Lambert Syndrome: A rare autoimmune disorder characterised by muscle weakness of the limbs
  • Myasthenia Gravis: A rare, long term illness that commonly affects the muscles of the eyes and eyelids, facial expressions, chewing, swallowing and speaking and other parts of the body.
  • Vasculitis: Inflammation of the blood vessels.
Screen Shot 2018-06-13 at 12.57.56.png

Resources

NICE Guidelines (2009): Rehabilitation following Critical Illness

Cochrane Review: Interventions for preventing critical illness polyneuropathy and critical illness myopathy

The development of a clinical management algorithm for early physical activity and mobilization of critically ill patients: synthesis of evidence and expert opinion and its translation into practice.

Guidelines for the Provision of Intensive Care Services

References

  1. Appleton, R. and Kinsella, J., 2012. Intensive care unit-acquired weakness. Continuing Education in Anaesthesia, Critical Care and Pain12(2), pp.62-66.
  2. Stevens, R.D., Marshall, S.A., Cornblath, D.R., Hoke, A., Needham, D.M., de Jonghe, B., Ali, N.A. and Sharshar, T., 2009. A framework for diagnosing and classifying intensive care unit-acquired weakness. Critical care medicine37(10), pp.S299-S308.
  3. 3.0 3.1 3.2 Zhou, C., Wu, L., Ni, F., Ji, W., Wu, J. and Zhang, H., 2014. Critical illness polyneuropathy and myopathy: a systematic review. Neural regeneration research9(1), p.101.
  4. 4.0 4.1 Hermans, G. and Van den Berghe, G., 2015. Clinical review: intensive care unit acquired weakness. Critical care19(1), p.274.
  5. 5.0 5.1 5.2 5.3 Visser, L.H., 2006. Critical illness polyneuropathy and myopathy: clinical features, risk factors and prognosis. European journal of neurology13(11), pp.1203-1212.
  6. Latronico, N. and Gosselink, R., 2015. A guided approach to diagnose severe muscle weakness in the intensive care unit. Revista Brasileira de terapia intensiva27(3), pp.199-201.
  7. Latronico, N. and Bolton, C.F., 2011. Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis. The Lancet Neurology10(10), pp.931-941.
  8. De Jonghe, B., Sharshar, T., Lefaucheur, J.P., Authier, F.J., Durand-Zaleski, I., Boussarsar, M., Cerf, C., Renaud, E., Mesrati, F., Carlet, J. and Raphaël, J.C., 2002. Paresis acquired in the intensive care unit: a prospective multicenter study. Jama288(22), pp.2859-2867.
  9. Wieske, L., Witteveen, E., Petzold, A., Verhamme, C., Schultz, M.J., van Schaik, I.N. and Horn, J., 2014. Neurofilaments as a plasma biomarker for ICU-acquired weakness: an observational pilot study. Critical Care18(1), p.R18.
  10. Hermans, G., De Jonghe, B., Bruyninckx, F. and Van den Berghe, G., 2008. Clinical review: critical illness polyneuropathy and myopathy. Critical care12(6), p.238.
  11. Shepherd, S., Batra, A. and Lerner, D.P., 2017. Review of critical illness Myopathy and neuropathy. The Neurohospitalist7(1), pp.41-48.
  12. Latronico, N. and Gosselink, R., 2015. A guided approach to diagnose severe muscle weakness in the intensive care unit. Revista Brasileira de terapia intensiva27(3), pp.199-201.
  13. NICE (2009). Rehabilitation after critical illness in adults. Available at: https://www.nice.org.uk/guidance/cG83 [Accessed 12th June 2018].
  14. Needham, D.M., 2008. Mobilizing patients in the intensive care unit: improving neuromuscular weakness and physical function. Jama300(14), pp.1685-1690.
  15. Kayambu, G., Boots, R. and Paratz, J., 2013. Physical therapy for the critically ill in the ICU: a systematic review and meta-analysis. Critical care medicine41(6), pp.1543-1554.    
  16. Chiang, L.L., Wang, L.Y., Wu, C.P., Wu, H.D. and Wu, Y.T., 2006. Effects of physical training on functional status in patients with prolonged mechanical ventilation. Physical therapy86(9), pp.1271-1281.    
  17. Rooney, K.A. and Thomas, N.J., 2010. Severe pulmonary hypertension associated with the acute motor sensory axonal neuropathy subtype of Guillain-Barré syndrome. Pediatric Critical Care Medicine11(1), pp.e16-e19.
  18. Pattanshetty, R.B. and Gaude, G.S., 2011. Critical illness myopathy and polyneuropathy-A challenge for physiotherapists in the intensive care units. Indian journal of critical care medicine: peer-reviewed, official publication of Indian Society of Critical Care Medicine15(2), p.78.