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NMweak - Neuromuscular Neuromuscular weakness in ICU DM...

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Unformatted text preview: Neuromuscular Neuromuscular weakness in ICU DM Seminar Dr. Alok Nath February 2006 INTRODUCTION INTRODUCTION ► Neuromuscular weakness is commonly encountered problem in ICU ► Abnormalities can be found in majority of patients within 1 or more weeks ► Spectrum ranges from isolated nerve entrapment with focal weakness to severe myopathy or neuropathy INTRODUCTION INTRODUCTION ► Less commonly recognized problem ► Electrophysiological abnormalities in more than 50% and overt clinical weakness in 2530 % in patients mechanically ventilated for more than 7 days (Leijten et al ) ► Large impact on morbidity and mortality Innervation of Respiratory muscles Innervation Muscle group Upper airway Level Palate, Pharynx Genioglossus IX, X, XI XII Nerve Glossopharyngeal Hypoglossal Inspiratory muscles Diaphragm Scalenes Parasternal intercostals Sternoceidomastoid Lat. Ext. intercostals C3-5 C4-8 T1-7 XI, C1, C2 T1-12 Phrenic Intercostals Spinal accessory Intercostals T7-L1 T1-12 Lumbar Intercostals Expiratory muscles Abdominal Internal intercostals Neuromuscular assessment Neuromuscular Respiratory muscular dysfunction may manifest in variety of ways and can interfere with function of: CNS CNS Spinal cord Spinal Peripheral nerves Peripheral NMJ NMJ Muscles Muscles Neuromuscular assessment Neuromuscular HISTORY AND PHYSICAL EXAM ► Index of suspicion Confirm weakness! Difficult weaning Difficult Presence of muscle atrophy Presence Neck weakness Neck Reversal with anticholinesterase Reversal ► Symptomatology (Cardinal and other) Upper airway involvement Upper Impairment of cough Impairment Sleep related abnormalities Sleep ► Drug history Neuromuscular assessment Neuromuscular ► Vitals ► Respiratory rate ► Mental status - not affected in CIPN/CIM ► Pattern of weakness symmetric, facial sparing symmetric, CN weakness - GBS, MG, BS stroke CN ► DTR - usually decreased if increased, suggests central lesion if Neuromuscular assessment Neuromuscular ► Recruitment of accessory muscles ► Ribcage and abdominal motions Bedside Bedside Magnetometry Magnetometry Inductance plethysmography Inductance Axial motion of chest wall can also be measured with magnetometry Neuromuscular assessment Neuromuscular GLOBAL ASSESSMENT Gas exchange and acid base status Ventilatory drive Ventilatory Partial pressures of O2 and CO2 Partial Alveolar arterial gradient Alveolar Sleep monitoring Sleep Polysomnography Polysomnography Neuromuscular assessment Neuromuscular Spirometry Restrictive pattern but RV is preserved till late Restrictive More than 25% ↓ in VC from upright to supine More highly suggestive of diaphragm weakness Usually FEV1 is normal or decreased Usually Maximum voluntary ventilation (weakness, poor Maximum coordination and reduced endurance) Spirometry insensitive measures of respiratory muscle weakness Neuromuscular assessment Neuromuscular Mouth pressures Simplest, most commonly used (Black and Hyatt) Simplest, Maximal Inspiratory Pressures( Muller's maneuver) Maximal Maximal Expiratory Pressures( Valsalva maneuver) Maximal Varies according to lung volumes Varies Generalized weakness ↓ both MIP and MEP Isolated diaphragm involvement may reduce only PI max Neuromuscular assessment Neuromuscular ► PImax and and PEmax values are effected with Age Age Sex Sex Type of mouth piece Type Lung volumes Lung Variable effort and learning Variable Simlified maneuver not requiring much patient effort required Neuromuscular assessment Neuromuscular Maximal Sniff pressures Reduces variability seen in MIP and MEP Reduces Easy to perform, No mouthpiece required Easy Initiated at FRC and either transdiaphragmatic Initiated (Pdi) esophageal (Pes) or nasal pressures (Pn) can be measured Pdi and Pn higher and less variability Pdi Neuromuscular assessment Neuromuscular Studies suggest that sniff pressure, More reliable than Muller's maneuver More Greater than Maximal static pressures Greater Fittilng JW et al 1999 Pn sniff measurements are test of global respiratory muscle function and give little information about diaphragm strength Neuromuscular assessment Neuromuscular SPECIFIC ASSESSMENT OF DIAPHRAGM Maximal transdiaphragmatic pressures ► Pdi = Pga – Pes Pdi – Trans diaphragmatic pressure Pga – Abdominal pressure Pes – Pleural pressure ► During quiet respiration change in Pdi = 10 cm of H2O Neuromuscular assessment Neuromuscular ► With inhalation to TLC, Pdi is typically greater than 30 cm H2O and may increase to values greater than150 cm H2O during maximal inspiratory efforts (i.e. Muller maneuver) ► The coefficient of variation for Pdi during maximal Muller efforts is large, whereas the variability of Pdi during a sniff maneuver is less and the magnitude of Pdi greater ► Greater values obtained with more complex maneuvers ( Combined maneuver) Neuromuscular assessment Neuromuscular ► Studies show that most reproducible results are seen with complex maneuvers Disadvantages of Pdi measurement ► Invasive ► Proper placement of catheter difficult in patients with profound weakness ► Complex and difficult to perform Neuromuscular assessment Neuromuscular Phrenic nerve stimulation ► Stimulated near the posterior triangle of neck with electric or magnetic stimulus ► Magnetic technique is non selective ► Demonstrates integrity of phrenic nerve ► Measuring Pdi following phrenic nerve stimulation assesses the mechanical output of the diaphragm Neuromuscular assessment Neuromuscular ► Conduction time of less than 9msec is normal ► Pdi following bilateral electric phrenic nerve stimulation is generally between 25 and 35 cm H2O ► Requires no patient effort ► But depends on impedance of abdomen and rib cage Neuromuscular assessment Neuromuscular Radiographic assessment Elevated hemi diaphragm Elevated Limited role in bilateral weakness Limited Fluoroscopy Fluoroscopy ► Quiet breathing ► Sniff test Ionizing radiation and poor specificity limit its role Ultrasound can be used to avoid radiation but specificity is unaffected Neuromuscular assessment Neuromuscular Imaging the diaphragm zone of apposition ► The zone of apposition is the area of the chest wall where the abdominal contents abut the lower rib cage ► With this approach, the contraction of the diaphragm muscle itself can be visualized Neuromuscular assessment Neuromuscular ► Diaphragm thickness (tdi) at end-expiration can be measured along with the change in tdi during inspiration ► Changes in tdi during inspiration are proportional to diaphragm shortening in adults and infants, whereas tdi measured at end-expiration is proportional to diaphragm strength Neuromuscular assessment Neuromuscular In the ICU the techniques which are useful are: Clinical assessment Clinical MIP and MEP MIP Transdiaphragmatic pressures Transdiaphragmatic Phrenic nerve stimulation Phrenic Radiographic assessment Radiographic Neuromuscular assessment Neuromuscular ► Ventilator measurements Pmus 0.1 ( preserved in neuromuscular weakness) 0.1 RSBI ( >105) RSBI Maximum inspiratory pressure (< 20 cm H2O) Maximum ► Integrated indices (e.g. CROP, SWI) Demand vs. work of breathing Demand ► Negative inspiratory force The 20 30 40 Rule FVC < 20ml/kg MIP < 30 cm of H2O MEP < 40 cm of H2O CLASSIFICATION CLASSIFICATION Neuromuscular weakness in critically ill Increased load Decrease neuromuscular capacity Weakness Fatigue Considerable degree of overlap between subgroups Increased load Increased Mechanisms Increased respiratory resistance Increased dynamic elastance Increased intrinsic PEEP Increased CO2 production Increased O2 consumption Increased dead space Increased respiratory drive Decrease NM capacity Decrease Weakness Hyperinflation Critical illness polyneuropathy Critical illness myopathy Sepsis related myopathy Ventilator associated respiratory muscle damage Medications Malnutrition Decrease NM capacity Decrease Fatigue Contractile fatigue Brief Prolonged Acute Delayed Hyperinflation Hyperinflation ► Tachypnea and the associated shortening of expiratory time can prevent complete lung emptying, leading to dynamic hyperinflation ► Dynamic hyperinflation is common in patients experiencing an exacerbation of COPD, and it also occurs in patients with pneumonia, acute respiratory distress syndrome, and chest trauma Critical illness polyneuropathy (CIPN) Critical ► Clinically significant muscle weakness in patients who achieve satisfactory awakening after at least 7 days of ventilation, has an incidence of 25% ► Electrophysiological incidence as high as 76% in patients with sepsis and 63-75% in patients with sepsis and MODS De Jonghe B et al 2002Tepper M et al 2000, Garnacho-Montero J et al 2001 Clinical features Clinical ► Delayed weaning from ventilation ► Sensorimotor polyneuropathy Generalized muscle atrophy Generalized Flaccid paralysis Flaccid Decreased/absent DTRs Decreased/absent Sensory abnormalities (light touch/pain) Sensory Cranial nerve sparing Cranial ► Physical exam often non diagnostic ► Electromyography and nerve biopsies reveal axonal degeneration, and muscle biopsies reveal denervation atrophy. ► Clinical improvement seen in about 60% to 90% of patients who survive intensive care. ► More than one-third of patients with severe involvement (quadriparesis and quadriplegia) display motor impairment after 2 years Leijten et al 1995 ,De Jonghe B et al 2002 ► Results from release of cytokines in patients with sepsis and multiple organ failure ► However, has also been reported in mechanically ventilated patients without evidence of sepsis or multiple organ failure ► The importance of critical illness polyneuropathy in causing ventilatory failure is controversial ► In one study the duration of mechanical ventilation was longer in patients with critical illness polyneuropathy Garnacho-Montero J et al 2001 ► Other studies have demonstrated that severity of MODS was actually responsible for difficult weaning and increased ICU stay ► Risk of developing CIPN is more in patient with severe encephalopathy ► Hyperglycemia has been associated with an increased risk of CIPNM in multiple studies ► Tight glycemic control achieved decrease in CIPNM Critical illness myopathy (CIM) Critical ► Has been described with different names like acute quadriplegic myopathy, thick filament myopathy, acute necrotizing myopathy of intensive care ► Neuromuscular blocking agents and steroids play a dominant role ► CIM and CIPN both can coexist ► ► ► Has been most frequently reported with bronchial asthma but also occurs in patient with COPD, solid organ transplants, leukemia, lymphoma Muscle biopsies are usually required Biopsies reveal general decrease in myofibrillar protein content general selective loss of thick filaments (myosin) within Type selective I and Type II fibers in up to 79% of patients who receive glucocorticoids for more than 2 weeks . patchy necrosis and regeneration (78%), mild patchy myopathy (14%), and atrophy of Type I and Type II fibers (7%) Larsson L et al 2000 , Lacomis D et al 1996 ► Indirect proteolysis of myosin filaments by activating calpain (a calcium-activated protease), cathepsins, lysosomal acid proteases, and the ubiquitin– proteasome pathway (a cytosolic ATPdependent protease system) ► Decrease in myosin content might also result from reduced myosin transcription . But not in acute paralysis ► Impaired muscle membrane excitability is probably more important during the acute stage Larsson L et al2000,Rich MM et al 1997, MMTiao G et al 1996 ► Effect on duration of ICU stay variable in different studies ► Final outcomes also have reported as quite variable Prolonged neuromuscular blockade Prolonged ► Nondepolarizing neuromuscular blocking drugs (NMBDs), are either benzylisoquinolinium (atracurium, cisatracurium, and doxacurium) or aminosteroid (pancuronium, vecuronium, pipecuronium, and rocuronium) in structure ► Important risk factors for pronged weakness are Renal failure Renal Hypermagnesemia Hypermagnesemia Metabolic acidosis Metabolic Female sex Female Concomitant use of antibiotics Concomitant (aminoglycosides, clindamycin) and steroids ► Usually improve with clearance of the agent from the body ► Duration ► Most of improvement is variable patients improve between 1 – 7 days after stopping the drug. Sepsis related myopathy Sepsis ► Mechanisms include the cytotoxic effect of nitric oxide and its metabolites, free radicals, and ubiquitin–proteasome proteolysis ► Immunohistochemical studies revealed the generation of peroxynitrite. Exposure of muscles to the amount of peroxynitrite found in patients caused an irreversible decrease in force generation ► These data suggest that sepsis decreases muscle force through the production of nitric oxide and its toxic by-products Lanone S et al 2000 ► This catabolism occurs primarily in Type II muscle fibers. The breakdown probably results from activation of the ubiquitin–proteasome proteolytic pathway secondary to release of tumor necrosis factor , interleukin-1, and interleukin-6 ► Decreased diaphragmatic contractility can be improved by the administration of specific scavengers of superoxide ions, hydrogen peroxide, and hydroxyl radicals Ventilator associated respiratory muscle damage Ventilator ► 20% decrease in diaphragmatic strength and a 30% decrease in the amplitude of compound action potentials evoked by phrenic nerve stimulation after five days (animal studies) ► Likely mechanisms for the damage include activation of ubiquitin–proteasome proteolysis, calpain proteolysis (non-ubiquitin–proteasome system), and oxidative stress Le Bourdelles G et al 1994, Yang L et al2002, Sassoon CS et al 2002 ► Data on humans sparse ► In a retrospective study of 13 infants who received uninterrupted ventilator assistance for at least 12 days before death, most diaphragmatic fibers appeared atrophic ► The development of atrophy was suggested by a smaller diaphragmatic muscle mass in these infants than in 26 infants who died after receiving mechanical ventilation for 7 days or less Cote HC et al 2002 Fatigue Fatigue Contractile fatigue ► Sufficiently large respiratory load is applied over a sufficiently long period ► Short-lasting fatigue results from accumulation of inorganic phosphate, accumulation failure of the membrane electrical potential to failure propagate beyond T-tubes, intramuscular acidosis intramuscular ► ► ► Long-lasting fatigue is consistent with the development of, and recovery from, muscle injury Load-induced injury occurs in two phases: an acute injury immediately after muscle contraction and a delayed or secondary injury Several mechanisms may contribute to the acute injury eccentric contractions eccentric activation of calpain (a calcium-dependent activation nonlysosomal protease), increased muscle temperature, increased excessive production of reactive oxygen species excessive Hypercapnia and antioxidant mechanisms plays a protective role Animal models Animal ► Delayed or secondary injury of the diaphragm is characterized by focal necrosis, flocculent degeneration of the sarcoplasm, influx of inflammatory cells, and sarcolemma disruption ► Delayed diaphragmatic injury is proportional to the load and peaks 3 days after applying the load ► Delayed injury decreases diaphragmatic force production at rest and it increases fatigability ► The sarcolemma disruption involves more Type I than Type II fibers and this mechanism may play a role in humans ► Sarcomere disruption has been reported in 18 patients with COPD ► Diaphragmatic damage has been reported in patients dying of asphyxia, sudden infant death syndrome, and status asthmaticus ► Whether or not critically ill patients develop either short lasting or long-lasting contractile fatigue of the respiratory muscles has not been clear ► In one controlled study the contractile response of the diaphragm to phrenic nerve stimulation was ↓ in nine patients who failed a weaning trial ► The weaning failure patients experienced a greater respiratory load and developed greater diaphragmatic effort than did the weaning success patients ► None developed a decrease in transdiaphragmatic twitch pressure elicited by phrenic nerve stimulation. ► Seven of the nine weaning failure patients had a tension–time index above 0.15 Laghi et al 2003 Role of muscle biopsy Role When should it be done? ► Any patient with un explained neuromuscular weakness in ICU without EMG/NCS c/w pure CIPN/CIM Normal sensory neurography Normal Low motor amplitudes Low Little spontaneous EMG activity Little Unexplained weakness in ICU Risk factors for prolonged neuromuscular blockade? No yes Neurophysiological testing (NCS,EMG) TOF stimulation No Results consistent with CIPN,AQM TOF fade or postttetanic response Trial of NMB reversal Partial or complete recovery yes No No yes Avoid reexposure, physical therapy Consider alternative diagnosis Muscle biopsy Persistent weakness Await for NMB clearance Transfer to rehabilitation centre Management Management Prevention ► Avoiding and limiting the dose and duration of neuromuscular blockade ► Judicious use of corticosteroids ► Peripheral nerve stimulation with measurement of the response to four equal pulses over 2 seconds (train of four, or TOF) is the “gold standard” for monitoring neuromuscular blockade in the operating room ► Has not shown to decrease the incidence but hastens recovery Management Management ► Pharmacologic reversal of neuromuscular blockade with a cholinesterase inhibitor may also be useful in establishing a diagnosis but recovery will likely be incomplete or shortlived in the presence of high concentrations of NMBDs or their metabolites ► Measures that reduce ICU length of stay may also decrease CIPNM Management Management ► Intensive insulin therapy has been shown to reduce the risk of CIPNM, leading to a dramatic reduction in the risk of developing CIPNM compared with control subjects (odds ratio, 0.4; 95% confidence interval, 0.28–0.57; p 0.0001) Van Den Berghe et al 2001 ► Efforts to prevent and aggressively treat sepsis will likely reduce the incidence of CIPNM ► Nitric oxide synthase inhibitors and pretreatment with dexamethasone may prevent may decrease the incidence of CIM in patient with sepsis Boczkowski et el 1996,Lin MC et al 1998 Management Management ► Pretreatment with glucocorticoid receptor (RU 38,486) antagonist has also shown to decrease the incidence of sepsis related myopathy Tioa et al 1996 ► Use of dantrolene to prevent increase intracellular calcium and antioxidants have also shown to decrease the occurrence of ventilator associated respiratory muscle damage Treatment Treatment ► Treatment consists primarily of waiting for clearance of NMBD ► At this point in time, no treatments for established CIPNM have been proven to be effective ► Reexposure to corticosteroids and/or NMBDs should be avoided, as relapse of myopathy has been reported after recovery from an initial incident followed by reexposure to high-dose corticosteroids Conclusions Conclusions ► Acquired NM weakness more common than recognized and may result in substantial excess morbidity, mortality, and costs. ► Understanding of ICU-acquired paresis remains incomplete and recognition of its importance has implications for clinical practice and future research Conclusions Conclusions ► Avoiding neuromuscular blocking agents, limiting corticosteroids, treating hyperglycemia with intensive insulin therapy, limiting end-organ dysfunction, such as low tidal volume ventilation for patients with ARDS. ► Screening for weakness to help plan treatment, avoid potential toxin reexposure, and identify patients for rehabilitative treatments ...
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