This patient is a 46-year-old female with a history of rheumatic heart disease, severe mitral stenosis, and ischemic heart disease who presented with worsening breathlessness and palpitations. She developed cardiogenic shock, acute kidney injury, coagulopathy, and metabolic encephalopathy during her hospital stay. Electrodiagnostic testing showed findings consistent with an axonal neuropathy. She had a prolonged critical care course complicated by infections and multi-organ dysfunction before passing away. Critical illness myopathy and polyneuropathy are common neuromuscular complications in critically ill patients that can lead to prolonged mechanical ventilation and recovery.

1. History
46 year old female
RVHD - severe MS -2012
S/P BMV -2013, 2018
IHD -CAG -DVD non critical ds
Severe LV dysfunction
Advised - medical management and MvR
Now came with ℅
Breathlessness - NYHA class 2—4
Palpitation since 4 days
ECG -AF FVR
RHD with severe Ms with severeLV
dysfunction with AKI (145/4.5)
Received 2 cycle of HD
Developed shock
Transferred to ssh for further
management
Case 1

2. SSH
13/01/2023
ER - unresponsive ,bradycardia
,hypoglycaemia
Inj. Adrenaline
No CPR
IMV - prvc mode
Admitted in IcU
Icu
Cardiogenic shock
Ischemic hepatitis
AKI
Coagulopathy
Metabolic encephalopathy

3. O/E -
Comatose
Hypotonia all 4 limb
Reflexes absent
Pupil - BERTL
? Metabolic enceph ? HIE ?
After 4 days
Eye opening +
Quadriparesis persist
MRI brain -
Normal
Small vessel ischemic changes
Neuro ref -
Hypotonia disproportionate to mri
finding
Adv -
NCV

4. NCV
NCV - reduced amplitude of CAMPs without conduction slowing or prolongation of
distal latencies. axonal neuropathy
Diagnosis of CIMN was made.
Later course in the hopsital- Patient had fever spikes, blood culture grew candida
tropicalis, ETT culture grew Acenatobacter , neurology refrence i/v/o
encephalopathy done, MRI brain with Angiography was done s/o vertebral aretry
occlusion and cortical edema. Hyperammonemia was also observed, develooped
anuria , aki needed 2 sessions of HD, persitant shock- inotropes and vasopressors
were continued. Blood produts given as needed, antibiotics and antifungals
optimised. Bradycardia 2 time CP arrest and CPR given twice ROSC achieved, was
being planned for Definative BMV but patient went into arrest again and could not
be revived.

5. Critical Illness Myopathy
&
Critical Illness Polyneuropathy

6. • Muscular weakness is not a new phenomenon in ICU, 1st described by
Aster in 1892
• Weakness is partly a consequence of improved survival in patients with
multiorgan failure and sepsis, but may be associated with treatments
administered in the intensive care unit (ICU).
• Neuromuscular weakness in the ICU is most often due to critical illness
myopathy (CIM), critical illness polyneuropathy (CIP), or a combination of
the two.
• Over the past two decades, improvements in survival after discharge
from the ICU probably have led to increased awareness of ICU-acquired
weakness. The magnitude of neuromuscular impairment in the increasing
population of patients undergoing post-ICU rehabilitation has come to the
attention of health care providers, patients, and families.

7. Risk Factors:
• Sepsis
• SIRS
• Multiorgan Failure (Renal, Hepatic)
• Long duration of Mechanical Ventilation
• Hyperosmalarity
• Low Serum Albumin
• Vasopressor Support
• Hyperglycemia
• Parenteral Nutrition
• Long term neuromuscular Blockade
• Corticosteroids ?
1)Schweickert, w. D. & Hall, J. iCU-acquired weakness. Chest 131, 1541–1549 (2007)
2) Lacomis, D. & Campellone, J. v. Critical illness neuromyopathies. Adv. Neurol. 88, 325–335 (2002)
3) Hermans, G., De Jonghe, B., Bruyninckx, F. & van den Berghe, G. interventions for preventing critical illness
polyneuropathy and critical illness myopathy. Cochrane Database of Systematic Reviews, issue 1. Art. No.:
CD006832. doi:10.1002/14651858.CD006832.pub2 (2009).

8. Wolfgang Et all, Nature Reviews Neurology
2009
Pathophysiology

9. Critical illness myopathy
• The most common form of ICU-acquired myopathy is CIM. (UpToDate)
• Also known as Acute quadriplegic myopathy and thick filament
myopathy.
• The major histopathologic finding in CIM is relatively selective loss of
myosin, which can be identified as a lack of reactivity to myosin
ATPase in non-necrotic fibers
• There is usually atrophy of myofibers, type 2 more than type 1.

10. Critical Care Polyneuropathy
• The second neuromuscular condition that is commonly acquired in
the ICU is CIP
• CIP appears to be a common complication of severe sepsis and is
thought to represent a neurologic manifestation of the systemic
inflammatory response syndrome (SIRS).
• The mechanism of axonal injury in CIP is unknown.
• However, speculation focuses on injury to the microcirculation of
distal nerves, causing ischemia and axonal degeneration

11. - Myosin ATPase (pH 9.4)-reacted frozen muscle section reveals atrophic, type 2 (dark) fibers,
patchy regions of reduced reactivity (arrows) in some type 1 (light) and type 2 fibers, and
absent staining (asterisks) in other fibers. Normal muscle is seen in the inset.

12. Critical Care Polyneuropathy
• The second neuromuscular condition that is commonly acquired in
the ICU is CIP
• CIP appears to be a common complication of severe sepsis and is
thought to represent a neurologic manifestation of the systemic
inflammatory response syndrome (SIRS).
• The mechanism of axonal injury in CIP is unknown.
• However, speculation focuses on injury to the microcirculation of
distal nerves, causing ischemia and axonal degeneration

13. Clinical Features:
• CIM – Several days, CIP- 2-3 Weeks
• Failure to wean a patient off ventilator is the weakness in absence of
an explainable pulmonary pathology is a common presentation.
• Distal and proximal flaccid muscle weakness, symmetrical, although
isolated limb weakness has been described
• Deep Tendon Reflexes can be absent.
• Unlike CIM, CIP can have distal sensory involvement (Often Difficult to
test since many patients are encephalopathic or under sedation)
• Facial and Opthalmic muscles spared most of the times
• If cranial nerve involvement occurs, GBS should be ruled out.
Lacomis D et al, Acute myopathy of intensive care: clinical,
electromyographic, and pathological aspects.

14. • For patients with CIM, sensation should be normal if it can be tested
reliably. Patients should at least grimace to pain stimuli even when
they are encephalopathic
• Combined CIM/CIP has clinical features that overlap the individual
but closely corresponding features of CIM and CIP

15. • The basic steps in the initial evaluation include:
• Identifying generalized weakness and assessing muscle strength
• Reviewing prehospital functional status and patient and family history of
conditions that might be causing or contributing to weakness
• Searching for factors associated with neuromuscular weakness related to
critical illness, including:
•Sepsis
•Multiorgan failure
•Mechanical ventilation
•Hyperglycemia
•Exposure to glucocorticoids and/or neuromuscular blocking agents
Evaluation & Diagnosis

16. Examination
• In an awake and cooperative patient with unfettered ability to voluntarily move
the limbs, muscle strength can be tested manually in each limb and graded on
the Medical Research Council (MRC) scale
• CIM can be distinguished from CIP if preservation of sensory function (indicative
of the former) can be demonstrated. (Difficult in ICU)

17. Neuroimaging
• Neuroimaging is indicated if the neurologic assessment of weakness is
unreliable, or if the evaluation reveals evidence that raises suspicion
for a CNS lesion. (MR preffered over CT)
Laboratory Evaluation
-It is reasonable to obtain a serum creatine kinase (CK) level in all patients
who have critical illness associated with weakness.
-An elevation in serum CK is usually present with CIM and supports the
diagnosis but can occur in the absence of CIM among patients treated with
intravenous glucocorticoids

18. • Lumar Puncture and CSF analysis to rule out - encephalitides, myelopathies,
and the acute motor axonal neuropathy form of Guillain-Barré syndrome (GBS)
(IF SUSPECTED)
• Electroencephalography (EEG) is appropriate in patients with altered
consciousness to evaluate for seizures.
• Muscle biopsy is rarely performed unless another treatable condition, such as
an inflammatory myopathy, is in the differential diagnosis.
• For patients with CIM or combined CIM and CIP, muscle biopsy and
histopathology can confirm the presence of myopathy. In CIP, muscle biopsy
findings are those of neurogenic atrophy.

19. Electrodiagnostics
Electroneuronography
Electromyography
Direct Muscle
Stimulation

20. Electroneuronography
• A motor response is induced by transcutaneous stimulation of a
peripheral nerve, and compound muscle action potentials (CMAPs)
from the corresponding distal muscle are recorded.
• To calculate motor nerve conduction velocity, stimulation at two
points along the nerve is required.
• Sensory or mixed nerve action potentials are obtained by stimulation
of a sensory or mixed nerve, respectively, with recording electrodes
being placed distal or proximal to the stimulating electrode.
• Abnormalities in motor and sensory nerve conduction point to a
neuropathic process.

21. * As CIP is a primary axonal neuropathy, CMAP and nerve action
potential amplitudes are characteristically reduced, whereas conduction
velocity, distal motor latencies and responses to repetitive nerve
stimulation are normal

22. • A sensory conduction examination might show decreased sensory
nerve action potential (SNAP) amplitudes, which confirms the
presence of a polyneuropathy.
• The SNAP amplitude can, however, be artificially reduced by the
presence of subcutaneous edema, which enhances the distance
between the recording electrode and the underlying nerve.

23. Electromyography
• Electromyography is performed by inserting a monopolar or bipolar
needle electrode into selected muscle.
• The standard procedure involves three steps.
• STEP1 –
In the first step, spontaneous and insertion activity is assessed.
Needle electrode insertion into a normal muscle at rest induces a brief
burst of insertion activity, but no obvious spontaneous activity.
But if spontaneous activity like fibrillation potentials and positive
sharp waves indicates denervation or myonecrosis, both of which
separate muscle fibers from their end-plate zone.

24. • STEP 2-
-Low-threshold, semi-rhythmically firing motor unit potentials (MUPs)
are recorded on slight voluntary activation of the muscle.
-The duration, amplitude, and number of phases of the MUPs are
assessed. In myopathic disorders, MUPs are short and of low amplitude.
STEP 3 -
-The third step assesses the response to maximum voluntary contraction.
Increasing the force of voluntary contraction increases the firing rate of MUPs
and produces systematic recruitment of additional MUPs.
In healthy individuals, a large number of overlapping MUPs are recorded at
maximum effort, creating a so called interference pattern.

25. Yunfen Wu et al Overview of the Application of EMG Recording in the
Diagnosis and Approach of Neurological Disorders , 2012
- Loss of functional motor units with axonal injury (as occurs in CIP) or conduction
block produces a reduced recruitment–interference pattern.
-Individuals with myopathic diseases such as CIM have the normal complement of
motor units but reduced numbers of functional muscle fibers, which results in a
normal interference pattern with decreased amplitude

26. • Unfortunately, standard nerve conduction tests
(electroneuronography) and electromyography often have
insufficient specificity for differentiating between polyneuropathy and
myopathy in critically ill patients.
1) The voluntary recruitment of motor units is often impossible
because the muscle is too weak, or the patient is sedated or unable
to cooperate for other reasons.
2) CIP and CIM both lead to a reduction in the amplitude of the
CMAPs, and in both conditions fibrillation potentials and/or
positive sharp waves can be seen, indicating denervation or primary
muscular problems.
3) The use of SNAP alterations to discriminate neuropathies from
myopathies can be problematic because many patients have
peripheral edema.

27. Direct Muscle Stimulation
• In this technique, which can be
applied in sedated patients at the
bedside, CMAPs are measured after
nerve stimulation (neCMAPs) and
direct muscle stimulation
(dmCMAPs).
• By analyzing the amplitudes of the
two responses, a mathematical ratio
between neCMAP and dmCMAP can
be calculated.

28. • An neCMAP:dmCMAP ratio ≥1 suggests either myopathy or a normal
clinical picture.
• Differentiation between CIM and normal muscle function can easily
be accomplished on the basis of the absolute value of the dmCMAP
amplitude—myopathy causes a loss of electrically excitable muscle,
leading to a reduction in the dmCMAP amplitude.
• A neCMAP:dmCMAP ratio <1 are seen in neuropathy
• Direct Muscle Stimulation although has so many advantages but it is
not readily available at all centres.

29. Evaluation & Diagnosis
STEP 1

30. STEP 2

31. STEP 3

32. Differential Diagnosis (UpToDate)

34. Histopathological features
CIM
-Muscle biopsies are considered to be the gold
standard.
-Three subtypes of ICU-acquired myopathies have been
morphologically described that are often grouped
together as acute quadriplegic myopathy
-Thick filament myopathy is the most common form of
ICU-acquired myopathy, and is characterized by
selective proteolysis and loss of myosin filaments
-In minimal change or cachectic myopathy, the muscle
fibers show caliber variations, angulations, internalized
nuclei, rimmed vacuoles, fatty degeneration, and
fibrosis.
- Necrotizing myopathy is characterized by muscle fiber
vacuolization and phagocytosis of myocytes
CIP
-Signs of axonal degeneration in both motor and
sensory nerve fibers, resulting in extensive denervation
atrophy of limb and respiratory muscles
-Angular atrophy of isolated scattered muscle fibers has
been observed as part of an acute denervation process.

35. Preventive and therapeutic approaches
• No specific therapy for the treatment of CIM and CIP. Consequently,
only preventive and supportive measures can currently be
recommended.
• The aggressive treatment of sepsis—the most important risk factor—
has highest priority in terms of reducing the incidence of CIM and CIP.
Furthermore, NMBAs and corticosteroids should be used at minimal
doses for as short a period as possible, although ‘stress doses’ of
steroids <250mg/ day have not shown to cause CINM.

37. • The effects of intensive
versus conventional insulin
therapy have been
prospectively studied in
surgical and medical ICU
patients.

38. • On the basis of pathogenetic considerations, several therapeutic
strategies have been proposed for the prevention of CIP and CIM.1
• These strategies include nutritional interventions, supplement and
antioxidant therapy (for example, substitution of glutamine, arginine,
nucleotides or omega-3 fatty acids), and the application of
testosterone derivates, growth hormones and immunoglobulins.
• There are some indications that early mobilization and
physiotherapy could improve outcomes in patients with CIP or CIM,
but this possibility is still open to debate.
1)Hermans, G., De Jonghe, B., Bruyninckx, F. Clinical review: polyneuropathy and myopathy.
2) Hermans, G. et al. Benefits of intensive insulin therapy on neuromuscular complications in routine
daily critical care practice: a retrospective study. Crit. Care 13, r5 (2009)
3) Hermans, G. 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. 175, 480–489
(2007)
4) Hermans, G., De Jonghe, B., Bruyninckx, F. & van den Berghe, G. interventions for preventing
critical illness polyneuropathy and critical illness myopathy. Cochrane Database of Systematic
Reviews, issue 1. Art. No.: CD006832. doi:10.1002/14651858.CD006832.pub2 (2009).
5) Garnacho-Montero, J. et al. Critical illness polyneuropathy: risk factors and clinical consequences.
A cohort study in septic patients. Intensive Care Med. 27, 1288–1296 (2001).

39. Prognosis
• Critical illness myopathy (CIM) is usually reversible over weeks to
months but leads to prolonged ICU stays and increased length of
hospital stay overall.
• Rehabilitation after critical illness is arduous and often frustratingly
slow, particularly in elderly patients.
• Patients who survive respiratory failure, circulatory failure (e.g., in
association with ARDS or sepsis), or both seem to have these
problems with the greatest frequency and intensity.
• Studies show that up to 65% of such patients have functional
limitations after discharge from the hospital.

40. • As mentioned earlier, in the past, routine features of general care
provided in the ICU included liberal use of sedation and
immobilization of the patient, which were thought to be necessary
for facilitating interventions to normalize physiological function by
artificial means. Recently, there has been a paradigm shift away from
this approach toward a “less is more” philosophy for patients in the
ICU.
• Herridge et al. followed a cohort of survivors of ARDS for 5 years after
hospital discharge.
1)Muscle weakness and functional impairment were frequently
observed at 1 year, and recovery from physical dysfunction was
incomplete even 5 years after discharge.
2) Elderly survivors of critical illness appear to fare particularly poorly
3) At the 5-year assessment, the results of 6-minute walk tests were
still only 70% of the predicted results.

41. Preventive Strategies
• The discontinuation of deep sedation is a critical first step in
optimizing patient activity and awareness.
• Moderate glucose control (Avoiding Hypoglycemia)
• Early mobilization
• Bailey and colleague reported on mobilization in a large cohort of
patients who required mechanical ventilation. These investigators
described a “culture change,” whereby activity was encouraged as
soon as the condition of patients was hemodynamically stable with
modest ventilator settings (i.e., fraction of inspired oxygen ≤0.6 and
positive end-expiratory pressure ≤10 cm of water).
• Limiting/avoiding use of NM Bloackers
• Despite controversy regarding causality, it still seems reasonable to
discontinue or reduce glucocorticoids as soon as possible.