Pediatric critical illness neuropathy

Author(s): Marina Ma, MD and Douglas G. Kinnett, MD

Originally published:09/20/2014

Last updated:05/29/2018

1. DISEASE/DISORDER:

Definition

Critical illness polyneuropathy (CIP) is a type of intensive care unit acquired weakness (ICU-AW). It is described as a distal axonal sensory-motor polyneuropathy affecting limb and respiratory muscles, and rarely the facial muscles. Limbs are usually affected symmetrically, distal more than proximal (1, 2).

CIP should be distinguished from critical illness myopathy (CIM), as prognosis may vary. However, the two often coexist and maybe difficult to differentiate. Subsequently, most of the current research on ICU-AW do not provide specific recommendations for interventions or outcome tracking for either CIP or CIM.

Etiology

The etiology of CIP has not been definitively determined in adults or children. An interaction of several metabolic and inflammatory factors affecting vascular flow and cell energy have been proposed (2-6). These factors would affect all organ systems, including nerve and muscle, subsequently leading to the development of CIP.

Epidemiology including risk factors and primary prevention

The incidence of CIP approached 100% in several reviews of adults with sepsis, inflammatory response and multi-organ injury (3, 6). The number is much lower in pediatric literature, as low as 0% to 28%. This is likely due to under-recognition by medical providers, lack of feasible and/or standardized diagnostic criteria, and parental refusal of invasive testing (7, 8).

As with adults, risk factors for pediatric CIP include sepsis, systemic inflammatory response, multi-organ failure, mechanical ventilation, hyperglycemia, renal replacement therapy, organ transplantation, toxic effects of drugs (corticosteroid, aminoglycosides, and neuromuscular blocking agents), burns, immobility, and older age. Additional factors reported in pediatric populations include asthma, higher Pediatric Index Mortality-2 score, and use of extracorporeal life support (2, 4-6, 8). Banwell also reported a bimodal age distribution with increased incidence in patients younger than 3 years old and older than ten years old (9).

Given the above risk factors, primary prevention of CIP consists of aggressive treatment of sepsis, insulin therapy to avoid hyperglycemia, minimizing sedation and medications that could be toxic to the peripheral nervous system, reducing the duration of immobilization, and early rehabilitation. Other than insulin therapy, no other pharmacological or nutritional recommendations have been made (2, 3, 5, 10).

Patho-anatomy/physiology

Latronico and Bolton proposed CIP to be the result of interaction between microvascular injury due to hyperglycemia and pro-inflammatory cytokines allowing penetration of toxic factors into the nerves, mitochondrial dysfunction, and sodium channel inactivation. All of the above factors lead to axonal degeneration, as seen in CIP (2-5).

Biopsies may show acute denervation with atrophy of type 1 and type 2 fibers in muscles and axonal degeneration in nerves (2-5).

Nerve conduction study typically reveals reduced amplitude of compound muscle action potential (CMAP) and sensory nerve action potential (SNAP), as well as normal to minimally reduced nerve conduction velocity. Direct muscle stimulation, on the other hand, will demonstrate preserved CMAP amplitude in CIP without CIM. No decremental response will be seen on repetitive nerve stimulation. Electromyography may show fibrillation potentials and positive sharp waves. Motor unit potential, if recordable, may initially be normal, but would later be polyphasic and large in amplitude (2-5, 11).

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

In one prospective study in children, muscle weakness was identified between days 4 and 26 of ICU admission, with most of the cases reported by day 14 (9). Weakness can persist for weeks to months, making weaning from ventilation difficult. Recovery is spontaneous but variable and can range from full recovery to persistent weakness or death (5, 6).

Specific secondary or associated conditions and complications

The prolonged immobility in CIP can lead to functional decline from the resulting profound weakness, compression neuropathies, muscle atrophy and joint contractures. It is then important to identify the presence of ICU-AW, including CIP, in comatose patients to prevent overly pessimistic prognostication resulting in inappropriate withdrawal of care (12). A study of PICU survivors in Netherland showed impairments in both neurocognitive and physical functioning post discharge in nearly 70% of the survivors. These may include difficulty concentrating, changes in behavior or mood, retardation in psychomotor development, change in voice production, and abnormal respiratory and neurological examination, amongst others (13).  Additional factors that may contribute to these sequela in combination with ICU-AW are PICU complications from procedures and continued underlying illness.

2. ESSENTIALS OF ASSESSMENT

History

In children with risk factors for developing CIP, a good premorbid functional history should be obtained so identification can be quickly made when their recovery is not progressing as expected. One must keep in mind the effect of sedative medication and respiratory deficits before attributing functional deficits to CIP.

Physical examination

CIP tends to involve all four limbs symmetrically, with increased prevalence in distal muscle groups. Muscle stretch reflexes are depressed or absent. Facial muscles tend to be spared so that painful stimulus in a patient with CIP may elicit movement only in the facial muscles, with none in the limbs. There may also be reduced or absent sensation to pain, temperature, vibration, or proprioception. If weakness has been longstanding, muscle atrophy may be present.

Functional assessment

Functional assessment may be limited by the presence of profound weakness, lack of understanding of the commands given during testing, or premorbid functional skill of the child. Manual muscle testing can be performed in those 4 years and older; for younger patients, observation and evaluation of movements can be effective. Scores of less than 48 in strength testing using the Medical Research Council (MRC) muscle scale indicate the presence of ICU-AW (2, 3). Keep in mind the developmental stage of the child when performing the assessment.

Laboratory studies

Serum creatine kinase is usually normal in CIP unless severe muscle necrosis in present. Elevation in plasma neurofilament, a biomarker of axonal injury, may be seen. Muscle biopsy is the gold standard and can distinguish between CIP or CIM; however, it is invasive and painful (3).

Supplemental assessment tools

Head imaging may be obtained in comatose patients to rule out a central nervous system pathology. Electrodiagnostic studies can be helpful in documenting the presence of nerve and/or muscle injury and distinguishing CIP from CIM and other neuromuscular dysfunction. If patients cannot move, these studies are less helpful in separating CIP from CIM. Other modalities include use of handheld dynamometry and handgrip strength, muscle ultrasound, and pulmonary function testing (5, 11).

Early predictions of outcomes

In general, ICU-AW is associated with prolonged ICU and hospital stay, prolonged duration of ventilator support, increased ICU and hospital morbidity and mortality, increased healthcare related hospitalization costs, decreased likelihood of being discharged directly to home, reduced functional outcomes and lower quality of life post discharge (5, 8, 11, 14).  Amongst those with ICU-AW, absence of detectable CMAP is a predictor of long-term functional disability (3).  There are no other reliable early predictors of outcome. Presence of CIP also portends a poorer prognosis compared to CIM alone.

Environmental

Identifying the home setting at discharge is necessary to determine services and equipment needed. Similarly, appropriate provisions for school attendance may be required, including those related to the school architecture, such as wheelchair ramps and accessible bathroom, and school services such as provision of an aide or scribe and extra time for assignments, available.

Social role and social support system

Having a supportive social system is important to any family dealing with a chronic condition such as CIP. Determining the ability of a family to provide constant care, to transport patients in a wheelchair (and to transfer them safely to and from the wheelchair), and to withstand the financial impacts that can result from the accommodations required by such conditions will be important at the time of discharge.

Professional Issues

Even though children with CIP can initially present with severe weakness and inability to communicate, it is important to address rehabilitation management and strategies to prevent the complications of immobility. With proper attention to these issues, many patients with CIP will have the potential for significant recovery and a good quality of life.

3. REHABILITATION MANAGEMENT AND TREATMENTS

At different disease stages

Acute setting:  the PICU UP! initiative showed early mobilization (EM) can be performed safely within the first three days of PICU admission. Activities performed included in-bed therapies such as range of motion, bed positioning and splinting, and mobility therapies such as sitting at edge of bed, sit to stand, transfer, ambulation, and play (15). A practice algorithm encouraging such practice has also been developed specifically for children with oncological diagnoses and those who are mechanically ventilated (16).

Subacute setting: once the patient is off ventilator support, reevaluation is done to determine the intensity of the rehabilitation program required at this stage. This can be continued inpatient therapy, transfer to the inpatient rehabilitation unit for a more aggressive therapy program, or an outpatient therapy program.

Chronic/stable: most children with ICU-AW can continue with persistent upper and lower extremity weakness months to years after discharge (9). The ongoing involvement of physical medicine and rehabilitation (PM&R) physicians during the chronic recovery phase is important for optimal outcome. The PM&R physician’s role includes determining the need for continued therapy and appropriate rehabilitation equipment, as well as addressing the long-term effects of reduced mobility.

Coordination of care

Early mobilization of children with ICU-AW requires a team approach to be successful. This team should consist of critical care medicine, consultant medical services, PM&R, respiratory therapy, physical therapy, occupational therapy, nursing, social worker, care management, and the patient’s family.

The intervention itself, ideally, should be interdisciplinary, structured, standardized in terms of workflow, and able to be customized to a specific acuity and functional level. Communication among team members to coordinate therapy in the complex setting of the ICU is imperative to ensure the success of early mobilization efforts. Dedicated team members from the listed disciplines are needed to break down barriers that would delay implementation so that a consistent and reliable program can be implemented in the ICU setting (15).

Patient & family education

Medical management dominates the attention of families in the early stages of a critical illness. That is understandable given the potentially life-threatening complications that can occur. Timely education of families about early mobilization and the concept of the rehabilitation team should be arranged when the patient is medically stable or earlier, if the care team deems it appropriate.

Emerging/unique Interventions

Previous outcome measures in critical care have focused on length of stay, mortality, respiratory status, and ability to return to premorbid activities. More recently, there has been an effort to explore more functional outcome measures, such as pediatric overall performance category, pediatric cerebral performance category, and Functional Status Scale (17, 18). For patients requiring more long-term therapy intervention, functional outcome measures typically used in the pediatric rehabilitation setting can be used to document functional changes over time (WeeFIM, Pediatric Evaluation of Disability Inventory, Gross Motor Function Measure).

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

  1. Consider the presence of ICU-AW in patients with risk factors as delineated above. A high index of suspicion is needed, as early diagnosis may be difficult, especially when the patient is still receiving sedation and/or paralytic drugs.
  2. When ICU-AW is suspected, assess muscle strength, if possible. MRC < 48 suggests the presence of ICU-AW. If physical examination is unreliable, obtain an electrodiagnostic study. Changes can be seen within 24 to 48 hours after onset of this condition and can precede clinic findings (19).
  3. Although muscle biopsy may be helpful in determining the degree of CIM versus CIP, there is not a consensus on routinely obtaining biopsies in children.
  4. Early mobility is a consistent recommendation in the literature for patients with ICU-AW.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND PRACTICE

Cutting edge concepts and practice

Direct muscle stimulation can help differentiate the degree of CIP from CIM. This technique is minimally invasive and can be done in children (20).

Researchers are currently looking into potential early biomarkers of ICU-AW such as miR-181a (Bloch 2015).

Early mobilization while the patient is still on ventilator support is possible with coordination of team members to reduce sedation and monitor respiratory status for adjustments to the ventilator (19, 21). Use of neuromuscular electrical stimulation for muscle atrophy, interactive video games, and cycle ergometry in bed-ridden patients have also been attempted (22-24).

The development of a standardized practice algorithm may promote early detection and rehabilitation of patients with CIP. This will hopefully result in reductions in previously discussed complications.

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

CIP may be more prevalent in the pediatric ICU population than studies currently suggest. This may be especially true in patients who are making progress because this diagnosis is less likely to be entertained in such circumstances.

CIP specific interventions with measurement of long-term outcomes are not well described in the pediatric population. Additionally, most of the studies to date are limited to single centers with small number of participants.

REFERENCES

  1. Bolton CF, Gilbert JJ, Hahn AF, Sibbald WJ. Polyneuropathy in critically ill patients. Journal of neurology, neurosurgery, and psychiatry. 1984;47(11):1223-31.
  2. Latronico N, Bolton CF. Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis. The Lancet Neurology. 2011;10(10):931-41.
  3. Hermans G, De Jonghe B, Bruyninckx F, Van den Berghe G. Clinical review: Critical illness polyneuropathy and myopathy. Critical care (London, England). 2008;12(6):238.
  4. Kress JP, Hall JB. ICU-acquired weakness and recovery from critical illness. The New England journal of medicine. 2014;371(3):287-8.
  5. Hermans G, Van den Berghe G. Clinical review: intensive care unit acquired weakness. Critical care (London, England). 2015;19:274.
  6. Williams S, Horrocks IA, Ouvrier RA, Gillis J, Ryan MM. Critical illness polyneuropathy and myopathy in pediatric intensive care: A review. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2007;8(1):18-22.
  7. Mahmoud AT, Tawfik MA, Abdella SAAE-N, Said NM. Critical illness myopathy and polyneuropathy in children admitted to the ICU. Menoufia Medical Journal. 2017;30(3):748.
  8. Field-Ridley A, Dharmar M, Steinhorn D, McDonald C, Marcin JP. ICU-Acquired Weakness Is Associated With Differences in Clinical Outcomes in Critically Ill Children. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2016;17(1):53-7.
  9. Banwell BL, Mildner RJ, Hassall AC, Becker LE, Vajsar J, Shemie SD. Muscle weakness in critically ill children. Neurology. 2003;61(12):1779-82.
  10. Shepherd SJ, Newman R, Brett SJ, Griffith DM. Pharmacological Therapy for the Prevention and Treatment of Weakness After Critical Illness: A Systematic Review. Critical care medicine. 2016;44(6):1198-205.
  11. Jolley SE, Bunnell AE, Hough CL. ICU-Acquired Weakness. Chest. 2016;150(5):1129-40.
  12. Latronico N, Fenzi F, Recupero D, Guarneri B, Tomelleri G, Tonin P, et al. Critical illness myopathy and neuropathy. Lancet (London, England). 1996;347(9015):1579-82.
  13. Knoester H, Bronner MB, Bos AP. Surviving pediatric intensive care: physical outcome after 3 months. Intensive care medicine. 2008;34(6):1076-82.
  14. Cunningham CJB, Finlayson HC, Henderson WR, O’Connor RJ, Travlos A. Impact of Critical Illness Polyneuromyopathy in Rehabilitation: A Prospective Observational Study. PM & R : the journal of injury, function, and rehabilitation. 2018;10(5):494-500.
  15. Wieczorek B, Ascenzi J, Kim Y, Lenker H, Potter C, Shata NJ, et al. PICU Up!: Impact of a Quality Improvement Intervention to Promote Early Mobilization in Critically Ill Children. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2016;17(12):e559-e66.
  16. Betters KA, Hebbar KB, Farthing D, Griego B, Easley T, Turman H, et al. Development and implementation of an early mobility program for mechanically ventilated pediatric patients. Journal of critical care. 2017;41:303-8.
  17. Fiser DH, Long N, Roberson PK, Hefley G, Zolten K, Brodie-Fowler M. Relationship of pediatric overall performance category and pediatric cerebral performance category scores at pediatric intensive care unit discharge with outcome measures collected at hospital discharge and 1- and 6-month follow-up assessments. Critical care medicine. 2000;28(7):2616-20.
  18. Pollack MM, Holubkov R, Glass P, Dean JM, Meert KL, Zimmerman J, et al. Functional Status Scale: new pediatric outcome measure. Pediatrics. 2009;124(1):e18-28.
  19. Fan E. Critical illness neuromyopathy and the role of physical therapy and rehabilitation in critically ill patients. Respiratory care. 2012;57(6):933-44; discussion 44-6.
  20. Rich MM, Bird SJ, Raps EC, McCluskey LF, Teener JW. Direct muscle stimulation in acute quadriplegic myopathy. Muscle & nerve. 1997;20(6):665-73.
  21. Munkwitz M, Hopkins RO, Miller Iii RR, Luckett PM, Hirshberg EL. A perspective on early mobilization for adult patients with respiratory failure: Lessons for the pediatric population. Journal of pediatric rehabilitation medicine. 2010;3(3):215-27.
  22. Abdulsatar F, Walker RG, Timmons BW, Choong K. “Wii-Hab” in critically ill children: a pilot trial. Journal of pediatric rehabilitation medicine. 2013;6(4):193-204.
  23. Choong K, Awladthani S, Khawaji A, Clark H, Borhan A, Cheng J, et al. Early Exercise in Critically Ill Youth and Children, a Preliminary Evaluation: The wEECYCLE Pilot Trial. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies. 2017;18(11):e546-e54.
  24. Cameron S, Ball I, Cepinskas G, Choong K, Doherty TJ, Ellis CG, et al. Early mobilization in the critical care unit: a review of adult and pediatric literature. Journal of critical care. 2015;30(4):664-72.

Original Version of the Topic

Douglas G. Kinnett, MD. PEDIATRIC CRITICAL ILLNESS NEUROPATHY. Original Publication Date: 5/29/2018

Author Disclosure

Marina Ma, MD
Nothing to Disclose

Douglas G. Kinnett, MD
Nothing to Disclose

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