DR. SACHIN ADUKIA

Critical illness polyneuropathyand myopathy

Definitions

Critical illness polyneuropathy (CIP) refers to ICU-acquired weakness with

electrophysiological evidence of an axonal polyneuropathy.

Critical illness myopathy (CIM) refers to ICU-acquired weakness with myopathy

that is documented electrophysiologically or histologically.

Critical illness neuromyopathy (CINMP) refers to electrophysiological or

histologic findings of both critical illness polyneuropathy and critical illness

myopathy.

History

Osler described neuromuscular dysfunction in patients with sepsis

Olsen reported peripheral neuropathy complicating protracted coma.

In 1977, myopathy was described in a patient with status asthmaticus

who received high doses of hydrocortisone and simultaneous

neuromuscular blockade.

Introduction

Neuromuscular weakness develops in ≥25 percent of patients who are ICU and ventilated for atleast 7 days

may result in a lifelong loss of function CIP first described by Bolton and colleagues in 1984

causes severe limb weakness prolonged weaning, increases stay in ICU compromises rehabilitation

Muscles involved in CIP/CIM

affects the limbs (particularly LL) in a symmetric pattern.

proximal predominant (shoulders and hip girdle)

involvement of respiratory muscles can impede weaning from

mechanical ventilation.

Facial and ocular muscles are rarely involved.

Autonomic features are not seen

Pathology in CIM

Also known as acute quadriplegic myopathy and thick filament myopathy

There is loss of thick filament myosin and Type II fiber atrophy, mainly with

proximal weakness

Pathologically classified into five subtypes:

(1) thick filament myopathy

(2) acute myopathy with scattered necrosis

(3) acute myopathy with diffuse necrosis

(4) disuse cachectic myopathy

(5) rhabdomyolysis

Postulated pathophysiology- CIM

Reduced muscle membrane excitability reduced uptake and release of calcium by the sarcoplasmic reticulum producing a

decrease in muscle contractility. Decreased contractile protein function and muscle fibre force generation. Mitochondrial dysfunction and bioenergetic failure with consequent reduction in

oxygen utilization and ATP production. Muscle denervation either pharmacological (neuromuscular block) or structural (CIP)

mechanisms produces an increased expression of corticosteroid receptors within myocytes, sensitizing them to the deleterious effects of corticosteroids.

Muscle atrophy during critical illness occurs - 3–4% decrease in muscle cross-sectional area per day. Is due to increased proteolysis, decreased protein synthesis, and increased apoptosis.

Pathology and Pathophysiology for CIP

dysfunctional microcirculation leads to neuronal injury and axonal

degeneration.

E-selectin expression in peripheral-nerve vascular endothelium, suggesting endothelial-

cell activation with microvascular leak and alterations in microvascular environment.

Hyperglycemia exacerbates this by inducing neural mitochondrial dysfunction

presents as morphological signs of axonal degeneration in both type 1 and type 2

fibers, resulting in extensive denervation atrophy of muscles

Clinical features

Muscle wasting is variable and frequently disguised by oedema.

flaccid and usually symmetrical weakness

Usually noted as lack of movement after regaining consciousness, loss of deep tendon

reflexes that had been present earlier

earliest sign may be facial grimacing without limb movement to pain

EOM involvement – warrants investigation for different aetiology

Facial muscles - relatively spared

CIP may show a distal loss of sensitivity to pain, temperature, and vibration

But difficult to assess sensory system in Critically ill patient

Autonomic function is not affected.

Difficulty in Weaning

Weaning problems - involvement of the phrenic nerves and the

diaphragm, and intercostal and other accessory respiratory muscles

Neuromuscular weakness typically becomes apparent during

attempted weaning

Full ventilatory support can trigger muscle atrophy within 72 hours

in adults Evidence of oxidative stress and protein breakdown in the muscles

Levine et al. noted atrophy in diaphragm myofibers within 18

hours of complete diaphragmatic inactivity

Jaber et al. reported a loss of diaphragmatic strength within hours

after initiating mechanical ventilation

Differential diagnosis

Diagnosis

Serum CK -not helpful since they are normal if muscle necrosis is absent or

scattered ,which is usually the case

Routine electrophysiological examination often times cannot discriminate

between CIP and CIM in critically ill, sedated, uncooperative or extremely

weak patients

Local oedema can interfere with optimal sensory nerve stimulation and

recording

To differentiate between CIP and CIM – patient co operation is needed for

voluntary motor unit potential recruitment

Muscle biopsy

CRIMYNE study

CRIMYNE for critical illness to monitor for CIM and/or CIP)

showed that serial electrodiagnostic studies are helpful in predicting

development of CIM and/or CIP

Diagnosis of ICU Associated weakness- ICUAW

Presence of 1, 2, 5, and either 3 or 4 from:

1. Weakness developing after the onset of critical illness

2. weakness being generalized (involving both proximal and distal muscles),

symmetrical, flaccid, and generally sparing the cranial nerves

3. Muscle power assessed by MRC sum score of 48 (or a mean score of , 4 in all

testable muscle groups) noted on 2 occasions separated by 24 h

4. Dependence on mechanical ventilation

5. Causes of weakness not related to the underlying critical illness excluded.

MRC Sum score

involves the assessment of muscle power from three movements of each limb:

shoulder abduction

elbow flexion

wrist extension

hip flexion

knee extension

ankle dorsi-flexion

The maximal power obtained for each movement is graded according to the

MRC scale and a score out of 60 is calculated

Prevention and therapy

Aggressive treatment of sepsis

Corticosteriods and Neuro-muscular blockade agents, if indicated, to use at minimal dose for shortest period

Rehabilitation programs

Avoiding additional pressure neuropathies by careful positioning

Several specific therapies have been mentioned – nutrition supplements, antioxidant therapy, testosterone derivatives, growth hormones immunoglobulins

NONE EFFECTIVE

Insulin therapy

Intensive insulin therapy- Insulin itself has some potential beneficial

effects

anti-inflammatory effects

endothelial protection,

improvement of dyslipemia, and

neuroprotective effects in animals

an anabolic hormone2 unpublished studies report that intensive insulin therapy (target blood

glucose 80 to 110 mg/dL) may lower the incidence of CIM and CIP

Physiotherapy and training

Applying an early activity protocol ICU environment may contribute unnecessarily to

immobilizationSedation substantially reduce the likelihood of ambulation

Electrical muscle stimulation

An RCT including 24 patients with COPD receiving MV showed that EMS

sessions of 30 minutes in 28 days significantly improves muscle strength

and decreases no. of days needed before mobilization to chair

results in a shorter duration MV and shorter ICU stay

does not require patient cooperation and can be applied to any muscle group

Recovery from CIP/ CIM

Patients who survive ARDS or sepsis or both have these problems with the greatest

frequency and intensity.

patients requiring prolonged mechanical ventilation, neuromuscular recovery is

typically prolonged and incomplete.

Up to 65% of such patients have functional limitations after discharge

Neuromuscular abnormalities may last for many years in some

A 1 year follow-up of 13 survivors from the CRIMYNE study showed

a mixture of tetraplegia, partial recovery, and full recovery in combined CIM/CIP

complete recovery in three to six months for CIM alone

minority of patients with CIP has persistent weakness.

Prognosis

CIPNM significantly increases the length of MV and the

lengths of ICU and hospital stay

Mortality increases from 19-56.5% to 48-84%

Recovery CIM > CIP > CINM

Conclusion

Critical illness myopathy and/or critical illness neuropathy are frequent and serious

complications to intensive care that:

– delay weaning from mechanical ventilation

– increase the stay in ICU

– compromise rehabilitation

- may result in a lifelong loss of function and in a reduction in quality of life.

Ensure maximal functional status for survivors of ICU stays using multimodal

therapeutic approach including:

– screening and early diagnosis is possible

– intensive insulin therapy

– minimal sedation

– early physiotherapy

– electrical muscle stimulation

References

Kress JP, Hall JB. ICU-acquired weakness and recovery from critical illness. New England Journal of

Medicine. 2014 Apr 24;370(17):1626-35.

Appleton R, Kinsella J. Intensive care unit-acquired weakness. Continuing Education in Anaesthesia,

Critical Care & Pain. 2012 Apr 1;12(2):62-6.

Ydemann M, Eddelien HS, Lauritsen A. Treatment of critical illness polyneuropathy and/or myopathy

a systematic review. Dan Med J. 2012 Oct 1;59(10):A4511.

Zhou C, Wu L, Ni F, Ji W, Wu J, Zhang H. Critical illness polyneuropathy and myopathy: a

systematic review. Neural regeneration research. 2014 Jan 1;9(1):101.

Bolton CF. Neuromuscular manifestations of critical illness. Muscle Nerve 2005; 32:140.

Hermans G, Wilmer A, Meersseman W, et al. Impact of intensive insulin therapy on neuromuscular

complications and ventilator dependency in the medical intensive care unit. Am J Respir Crit Care

Med 2007; 175:480

Thank You