1. LSC Respiratory Conference Critical illness Myopathy & Critical illness Polyneuropathy By Elizabeth Kelley Buzbee AAS, RRT-NPS, RCP Lone Star System- Kingwood Updated September 2010

3. Failure to wean due to muscle weakness The effect of invasive mechanical ventilation on the patient’s ventilatory skeletal muscles is a well-known yet fairly complex problem. The effect of invasive mechanical ventilation on the patient’s ventilatory skeletal muscles is a well-known yet fairly complex problem. Full ventilatory support can trigger muscle atrophy within 72 hours in adults. Full ventilatory support can trigger muscle atrophy within 72 hours in adults. According to MacIntyre, both muscle mass and cross-section of muscle fibers are affected. [MacIntyre pp. 1http://www.medscape.com/viewarticle/514526] According to MacIntyre, both muscle mass and cross-section of muscle fibers are affected. [MacIntyre pp. 1http://www.medscape.com/viewarticle/514526]http://www.medscape.com/viewarticle/514526

4. Failure to wean continued “There is….. evidence of oxidative stress and protein breakdown in the muscles.” [MacIntyre pp. 1] “There is….. evidence of oxidative stress and protein breakdown in the muscles.” [MacIntyre pp. 1] When a patient’s FRC is raised above normal by PPV, the effect on resting muscle length results in a decrease in muscle strength. [MacIntyre pp. 1] When a patient’s FRC is raised above normal by PPV, the effect on resting muscle length results in a decrease in muscle strength. [MacIntyre pp. 1] Alterations in the blood flow to the ventilatory muscles secondary to PPV just adds to the problem. [ MacIntyre pp. 1] Alterations in the blood flow to the ventilatory muscles secondary to PPV just adds to the problem. [ MacIntyre pp. 1] Not only is muscle strength affected, we will see a decrease in muscle endurance. [MacIntyre pp. 1] Not only is muscle strength affected, we will see a decrease in muscle endurance. [MacIntyre pp. 1]

5. Other problems are more subtle malnutrition & electrolyte imbalances: malnutrition & electrolyte imbalances: The effects of malnutrition on the pulmonary system are distinct and well known. The effects of malnutrition on the pulmonary system are distinct and well known. Patients who cannot take oral nutrition may be on IV glucose, which is fine for a day or so, but TPN with its more complete nutritional support is needed to keep metabolism going. Patients who cannot take oral nutrition may be on IV glucose, which is fine for a day or so, but TPN with its more complete nutritional support is needed to keep metabolism going. Carbohydrates are needed for both the diaphragm and the myocardium [Peters pp. 350] Carbohydrates are needed for both the diaphragm and the myocardium [Peters pp. 350]

6. Other problems cont The effect of electrolyte imbalances on the myocardium is well-known but potassium levels can also affect skeletal muscle action of the chest and abdominal muscles. The effect of electrolyte imbalances on the myocardium is well-known but potassium levels can also affect skeletal muscle action of the chest and abdominal muscles. Hypokalemia can cause muscle weakness even paralysis [Garth] Hypokalemia can cause muscle weakness even paralysis [Garth] while hyperkalemia also results in muscle weakness and flaccid paralysis while hyperkalemia also results in muscle weakness and flaccid paralysis serum magnesium levels of 8.0-10.0 mEq/L are associated with flaccid skeletal muscle paralysis. [Novello ] serum magnesium levels of 8.0-10.0 mEq/L are associated with flaccid skeletal muscle paralysis. [Novello ]

7. Steroids and myopathy “Steroid myopathy is usually an insidious disease process that causes weakness mainly to the proximal muscles of the upper and lower limbs and to the neck flexors. “Steroid myopathy is usually an insidious disease process that causes weakness mainly to the proximal muscles of the upper and lower limbs and to the neck flexors. Cushing originally described it in 1932, and Muller & Kugelberg first studied it systemically in 1959.” Cushing originally described it in 1932, and Muller & Kugelberg first studied it systemically in 1959.” http://emedicine.medscape.com/article/313842-overview http://emedicine.medscape.com/article/313842-overview http://emedicine.medscape.com/article/313842-overview

8. The new threat in the ICU There are new problems discovered in the ICU that result in various degrees of muscle weakness--even paralysis-- that can keep a person from weaning off mechanical ventilation [Dhand pp. 1025] There are new problems discovered in the ICU that result in various degrees of muscle weakness--even paralysis-- that can keep a person from weaning off mechanical ventilation [Dhand pp. 1025] But is this a new problem? A review of the literature shows that as early as the 1970s, a small number of severe asthmatic patients who were intubated, paralyzed and ventilated had significant, generalized muscle weakness. But is this a new problem? A review of the literature shows that as early as the 1970s, a small number of severe asthmatic patients who were intubated, paralyzed and ventilated had significant, generalized muscle weakness. Critical illness polyneuropathy Critical illness polyneuropathy Critical illness myopathy Critical illness myopathy Prolonged neuromuscular blockage Prolonged neuromuscular blockage

9. Occurrence of CIP, CIM or a combination of the two as many as 30-50% of patients with critical illness. [Dhand pp. 1026] as many as 30-50% of patients with critical illness. [Dhand pp. 1026] Another study [n=206] found 25% of critical care patients who had been mechanically ventilated for more than 7 days had a degree of muscle weakness. This study included only persons who were awake and responsive [Deems pp. 1043] Another study [n=206] found 25% of critical care patients who had been mechanically ventilated for more than 7 days had a degree of muscle weakness. This study included only persons who were awake and responsive [Deems pp. 1043]

10. Critical illness myopathy

11. In the case of CIM, we seem to have a syndrome of In the case of CIM, we seem to have a syndrome of ‘symmetric weakness of all extremities, ‘symmetric weakness of all extremities, of muscle wasting, of muscle wasting, hyporeflexia hyporeflexia and failure to wean from mechanical ventilation.’ [Dhand pp. 1036] and failure to wean from mechanical ventilation.’ [Dhand pp. 1036]

12. Risk factors for Critical illness myopathy Persons who have received high levels of corticosteroids & neuromuscular blocking agents Persons who have received high levels of corticosteroids & neuromuscular blocking agents for diseases such as severe asthma, COPD exacerbation, sepsis, ARDS and s/p organ transplants. [Dhand pp. 1036] for diseases such as severe asthma, COPD exacerbation, sepsis, ARDS and s/p organ transplants. [Dhand pp. 1036]

13. S/S of Critical illness myopathy Inspection and interview of the patient There also seem to be is little in the inspection and interview to differentiate between critical illness myopathy and critical illness polyneuropathy. There also seem to be is little in the inspection and interview to differentiate between critical illness myopathy and critical illness polyneuropathy. The patient will c/o weakness in both situations. The patient will c/o weakness in both situations.

14. S/S of Critical illness myopathy Serum Creatine Kinase a product of muscle damage. Need to differentiate between myocardial CK and skeletal muscle CK. [Egan’s pp. 351] a product of muscle damage. Need to differentiate between myocardial CK and skeletal muscle CK. [Egan’s pp. 351] “Normal levels of serum creatine kinase are usually between 25 and 200 U/L. This test is not specific for the type of CK that is elevated.” [http://en.wikipedia.org/wiki/Creatine_kinase] “Normal levels of serum creatine kinase are usually between 25 and 200 U/L. This test is not specific for the type of CK that is elevated.” [http://en.wikipedia.org/wiki/Creatine_kinase]http://en.wikipedia.org/wiki/Creatine_kinase Serum creatine kinase may be 10-100 x higher than normal in CIM in the first 3-4 days-- then stabilize after 10 days. [Dhand pp. 1028] Serum creatine kinase may be 10-100 x higher than normal in CIM in the first 3-4 days-- then stabilize after 10 days. [Dhand pp. 1028]

15. S/S of Critical illness myopathy EMG: the electromyogram During this study the patient has auditory or visual stimuli to help them know when they are activating the muscle. the action potential is measured During this study the patient has auditory or visual stimuli to help them know when they are activating the muscle. the action potential is measured http://en.wikipedia.org/wiki/Electromyography http://en.wikipedia.org/wiki/Electromyographyhttp://en.wikipedia.org/wiki/Electromyography It is possible to perform an EMG of the phrenic nerve by placing the percutaneous electrode onto the neck at the supraclavicular fossa and measurements will be made at two spots along the anterior rib cage, It is possible to perform an EMG of the phrenic nerve by placing the percutaneous electrode onto the neck at the supraclavicular fossa and measurements will be made at two spots along the anterior rib cage, but the presence of a central line in either neck will make this EMG impossible. [Dhand pp. 1031- 1032] but the presence of a central line in either neck will make this EMG impossible. [Dhand pp. 1031- 1032]

16. S/S of Critical illness myopathy EMG results In myopathic disorders there will be decreases in duration of the action potential In myopathic disorders there will be decreases in duration of the action potential and in the ratio of area to amplitude and in the number of motor unit in the muscles [worse cases only] [http://en.wikipedia.org/wiki/Amplitude] and in the ratio of area to amplitude and in the number of motor unit in the muscles [worse cases only] [http://en.wikipedia.org/wiki/Amplitude]http://en.wikipedia.org/wiki/Amplitude

17. S/S of Critical illness myopathy Nerve conduction study the patient is given an electrical shock at various spots along a nerve. the patient is given an electrical shock at various spots along a nerve. Among other measurements, the velocity of the nerve conduction is measured at different points, as is the intensity of the response [amplitude.] Among other measurements, the velocity of the nerve conduction is measured at different points, as is the intensity of the response [amplitude.] The tester will study both the motor and the sensory nerve conduction. http://en.wikipedia.org/wiki/Nerve_conduction_study The tester will study both the motor and the sensory nerve conduction. http://en.wikipedia.org/wiki/Nerve_conduction_study http://en.wikipedia.org/wiki/Nerve_conduction_study In the case of CIM, there should be no real problems with conduction In the case of CIM, there should be no real problems with conduction

18. S/S of Critical illness myopathy Problems w/ Nerve conduction studies in the ICU: the patient’s skin temperature will change the speed of conduction; cool bodies result in slow conduction the patient’s skin temperature will change the speed of conduction; cool bodies result in slow conduction and the presence of pacemakers & indwelling defibrillators can make for difficulties [ MedlinePlus: nerve conduction studies] and the presence of pacemakers & indwelling defibrillators can make for difficulties [ MedlinePlus: nerve conduction studies]

19. S/S of Critical illness myopathy What are we left with? What are we left with? Muscle and nerve biopsy Both muscle and nerve biopsy can differentiate between CIP and CIM and even combinations of both disorders. [Dhand pp.1033] Both muscle and nerve biopsy can differentiate between CIP and CIM and even combinations of both disorders. [Dhand pp.1033]

20. Critical illness polyneuropathy

21. The Merck manual describes polyneuropathy as “the simultaneous malfunction of many peripheral nerves throughout the body.” The Merck manual describes polyneuropathy as “the simultaneous malfunction of many peripheral nerves throughout the body.” In CIP, on biopsy, one sees …both motor and sensory degeneration without inflammation. [Dhand pp. 1033] In CIP, on biopsy, one sees …both motor and sensory degeneration without inflammation. [Dhand pp. 1033]

22. Risk factors for polyneuropathy “Poor control of blood sugar levels in diabetes causes several forms of polyneuropathy, collectively referred to as diabetic neuropathy.” [Merck Manual] “Poor control of blood sugar levels in diabetes causes several forms of polyneuropathy, collectively referred to as diabetic neuropathy.” [Merck Manual] Diphtheria toxins, autoimmune reaction, heavy metals such as lead and mercury and CO poisoning can all lead to polyneuropathy. Diphtheria toxins, autoimmune reaction, heavy metals such as lead and mercury and CO poisoning can all lead to polyneuropathy. The drugs include Dilantin, & some antibiotics (such as nitrofurantoin and sulfonamides), some chemotherapy drugs and some sedatives such as barbital. [Merck Manual] The drugs include Dilantin, & some antibiotics (such as nitrofurantoin and sulfonamides), some chemotherapy drugs and some sedatives such as barbital. [Merck Manual]

23. Risk factors for Critical illness polyneuropathy History of sepsis, trauma, burn followed by organ failure, septic encephalopathy. [Dhand pp. 1033.] History of sepsis, trauma, burn followed by organ failure, septic encephalopathy. [Dhand pp. 1033.] in addition, according to the CDC, CIP is associated with a recent history of SIRV [septic inflammatory response syndrome. [ CDC ] http://www.cdc.gov/nchs/data/icd9/icd501a.pdf in addition, according to the CDC, CIP is associated with a recent history of SIRV [septic inflammatory response syndrome. [ CDC ] http://www.cdc.gov/nchs/data/icd9/icd501a.pdf http://www.cdc.gov/nchs/data/icd9/icd501a.pdf

24. S/S critical illness polyneuropathy On inspection: Because cranial nerves are generally unaffected in CIP, the patient’s facial grimace and limb movement on painful stimulation may be strikingly different. [CDC] Because cranial nerves are generally unaffected in CIP, the patient’s facial grimace and limb movement on painful stimulation may be strikingly different. [CDC] A muscle biopsy would show neuropathic changes. [Dhand pp. 1034.] A muscle biopsy would show neuropathic changes. [Dhand pp. 1034.]

25. S/S critical illness polyneuropathy He have a normal Creatine kinase. [Dhand pp. 1034.] He have a normal Creatine kinase. [Dhand pp. 1034.] he would have a reduction in both motor & sensory nerve conduction. [Dhand pp. 1029.] he would have a reduction in both motor & sensory nerve conduction. [Dhand pp. 1029.]

26. S/S critical illness polyneuropathy EMG results the EMG showed action potentials twice normal the EMG showed action potentials twice normal increased fibers per motor unit increased fibers per motor unit increase in duration of the action potential. [http://en.wikipedia.org/wiki/Amplitude] increase in duration of the action potential. [http://en.wikipedia.org/wiki/Amplitude]http://en.wikipedia.org/wiki/Amplitude

27. Prolonged neuromuscular blockage Nondepolarizing neuromuscular blocking agents such as pancuronium generally have duration of action of a few hours, but a few patients may suffer persistent weakness that can prevent successful weaning from ventilatory support. Nondepolarizing neuromuscular blocking agents such as pancuronium generally have duration of action of a few hours, but a few patients may suffer persistent weakness that can prevent successful weaning from ventilatory support. This paralysis could last additional hours--- or even weeks. [Dhand pp. 1037] This paralysis could last additional hours--- or even weeks. [Dhand pp. 1037]

28. Prolonged neuromuscular blockage

29. Prolonged neuromuscular blockage with nondepolarizing blocking agents results in metabolites. Prolonged neuromuscular blockage with nondepolarizing blocking agents results in metabolites. “Prolonged neuromuscular blockade after the termination of long-term treatment with vecuronium is associated with metabolic acidosis, elevated plasma magnesium concentrations, female sex, and probably more important, the presence of renal failure, and high plasma concentrations of 3-desacetylvecuronium.” [V Segredo] “Prolonged neuromuscular blockade after the termination of long-term treatment with vecuronium is associated with metabolic acidosis, elevated plasma magnesium concentrations, female sex, and probably more important, the presence of renal failure, and high plasma concentrations of 3-desacetylvecuronium.” [V Segredo]

30. Differential DX

31. Polyneuropathies such as Guillian Barre syndrome can be triggered by infection, Polyneuropathies such as Guillian Barre syndrome can be triggered by infection, while exacerbations of myasthenia gravis [MG crisis] can be triggered by stress, certain medications and illness. while exacerbations of myasthenia gravis [MG crisis] can be triggered by stress, certain medications and illness. Spinal cord infarction is a complication of aortic surgery [Dhand pp. 1026.] Spinal cord infarction is a complication of aortic surgery [Dhand pp. 1026.] myotonic dystrophy may have been undiagnosed myotonic dystrophy may have been undiagnosed

32. Differential DX Guillian Barre. There are no … antibodies in the serum of patients with critical illness polyneuropathy as would be seen with Guillian Barre. http://jnnp.bmj.com/cgi/content/extract/68/3/397 There are no … antibodies in the serum of patients with critical illness polyneuropathy as would be seen with Guillian Barre. http://jnnp.bmj.com/cgi/content/extract/68/3/397 http://jnnp.bmj.com/cgi/content/extract/68/3/397

33. Differential DX myasthenia gravis. Patients have increasing muscle weakness with repetitive motions Patients have increasing muscle weakness with repetitive motions they also antibodies against acetylcholine receptors they also antibodies against acetylcholine receptors tendency to have a degree of facial paralysis [inability to protect the airway], tendency to have a degree of facial paralysis [inability to protect the airway], a transient improvement when given cholinesterase inhibitors. [Egan’s pp. 576] a transient improvement when given cholinesterase inhibitors. [Egan’s pp. 576]

34. Differential DX Spinal cord infarction Comes on suddenly and catostrophically with 80% c/o severe pain Comes on suddenly and catostrophically with 80% c/o severe pain http://www.emedicine.com/NEURO/topic3 48.htm http://www.emedicine.com/NEURO/topic3 48.htm http://www.emedicine.com/NEURO/topic3 48.htm http://www.emedicine.com/NEURO/topic3 48.htm

35. Differential DX myotonic dystrophy Persons with myotonic dystrophy have increased sensitivities not only to paralytic agents, but to CNS depressants. [Egan’s pp. 576] Persons with myotonic dystrophy have increased sensitivities not only to paralytic agents, but to CNS depressants. [Egan’s pp. 576]

36. Treatment? According to the CDC, there are no medications for these problems, rather we need to consider ‘conservative management.’ [CDC] According to the CDC, there are no medications for these problems, rather we need to consider ‘conservative management.’ [CDC]

37. We need to stop killing black widow spiders with a sledge hammer.

38. May just tear up the house

39. Long term effects? One multicenter study of survivors of CIP or CIM or CIP/CIM, in which the patients were followed up that included muscle strength testing and nerve conduction studies at 3, 6 and 9 months found that 15 of 28 (53.6%) patients ….. had persisting neurological and electrophysiological signs of neuromuscular abnormalities on discharge from the acute care hospital. ( B Guarneri,) One multicenter study of survivors of CIP or CIM or CIP/CIM, in which the patients were followed up that included muscle strength testing and nerve conduction studies at 3, 6 and 9 months found that 15 of 28 (53.6%) patients ….. had persisting neurological and electrophysiological signs of neuromuscular abnormalities on discharge from the acute care hospital. (B Guarneri,) Of these 33.3% recovered normal muscle strength and global motor performance within 3 months ….. whereas 66.7% experienced prolonged and severely disabling muscle weakness and paralysis. Of these 33.3% recovered normal muscle strength and global motor performance within 3 months ….. whereas 66.7% experienced prolonged and severely disabling muscle weakness and paralysis. Patients with a definite diagnosis of CIM recovered earlier and better than those with CIP, the majority of whom remained severely disabled 1 year after hospital discharge. Patients with a definite diagnosis of CIM recovered earlier and better than those with CIP, the majority of whom remained severely disabled 1 year after hospital discharge. The average age of these mostly male [80%] patients was 44.7 years and none of them were treated for asthma The average age of these mostly male [80%] patients was 44.7 years and none of them were treated for asthma

40. What to do? Conservative measures w/ steroids According to the American Heart Association 2005 CPR guidelines, severe asthma needs to be treated with systemic steroids rather than topical: According to the American Heart Association 2005 CPR guidelines, severe asthma needs to be treated with systemic steroids rather than topical: but maybe we need more studies to be done with inhaled dosages so that the systemic side effects such as myopathy can be minimized? but maybe we need more studies to be done with inhaled dosages so that the systemic side effects such as myopathy can be minimized? In these studies, how are these patients given inhaled steroids? [mixed with Beta II or alone? SVN or MDI, DPI? ] In these studies, how are these patients given inhaled steroids? [mixed with Beta II or alone? SVN or MDI, DPI? ] Exactly what are the links between steroid-induced diabetes and neuropathy: how much steroid is too much? Exactly what are the links between steroid-induced diabetes and neuropathy: how much steroid is too much?

41. Conservative measures w/ steroid TX could we use offline measurements for intubated patients? could we use offline measurements for intubated patients? Research is on going on the question of using exhaled nitric oxide monitors to fine-tune the level of systemic steroids in the acute asthmatic. [Phua pp. 857] Research is on going on the question of using exhaled nitric oxide monitors to fine-tune the level of systemic steroids in the acute asthmatic. [Phua pp. 857] Offline measurement of FE NO has been compared favorably with online modes Offline measurement of FE NO has been compared favorably with online modes One UK single-blind study over a period of 8 months [n =116] showed no clinically significant improvement in controlling patient’s steroid dosages by monitoring FENO http://ajrccm.atsjournals.org/cgi/content/abstract/176/3/ 231 One UK single-blind study over a period of 8 months [n =116] showed no clinically significant improvement in controlling patient’s steroid dosages by monitoring FENO http://ajrccm.atsjournals.org/cgi/content/abstract/176/3/ 231 http://ajrccm.atsjournals.org/cgi/content/abstract/176/3/ 231 http://ajrccm.atsjournals.org/cgi/content/abstract/176/3/ 231

42. Conservation of steroid TX “Fluorinated steroids seem to produce weakness and myopathy more frequently than do nonfluorinated ones. “ “Fluorinated steroids seem to produce weakness and myopathy more frequently than do nonfluorinated ones. “ http://emedicine.medscape.com/article/313842-overview http://emedicine.medscape.com/article/313842-overview http://emedicine.medscape.com/article/313842-overview “In cases of myopathy caused by long-term corticosteroid use, decreasing the corticosteroid dose to below a 30 mg/d threshold may result in resolution of muscle weakness” “In cases of myopathy caused by long-term corticosteroid use, decreasing the corticosteroid dose to below a 30 mg/d threshold may result in resolution of muscle weakness” http://emedicine.medscape.com/article/313842-overview http://emedicine.medscape.com/article/313842-overview http://emedicine.medscape.com/article/313842-overview

43. Conservation of steroid “Preliminary studies on rats suggest that creatine plays a part in the prophylaxis of steroid-induced myopathy” “Preliminary studies on rats suggest that creatine plays a part in the prophylaxis of steroid-induced myopathy” http://emedicine.medscape.com/article/313842-overview http://emedicine.medscape.com/article/313842-overview http://emedicine.medscape.com/article/313842-overview Various medications, including potassium supplements, phenytoin, vitamin E, and anabolic steroids, have been tried as potential treatments for steroid myopathy. 5 None have been clearly shown to prevent or reverse muscle weakness induced by steroid myopathy. Various medications, including potassium supplements, phenytoin, vitamin E, and anabolic steroids, have been tried as potential treatments for steroid myopathy. 5 None have been clearly shown to prevent or reverse muscle weakness induced by steroid myopathy.vitamin Eanabolic steroidsvitamin Eanabolic steroids

44. Possible rehab for steroid- induced myopathy “Some literature suggests that aerobic exercises and resistance training may help to prevent weakness or reduce its severity. ………… However, high intensity exercise should be avoided, because, according to some preliminary animal research models, it may be harmful.” http://emedicine.medscape.com/article/313842- overview “Some literature suggests that aerobic exercises and resistance training may help to prevent weakness or reduce its severity. ………… However, high intensity exercise should be avoided, because, according to some preliminary animal research models, it may be harmful.” http://emedicine.medscape.com/article/313842- overview http://emedicine.medscape.com/article/313842- overview http://emedicine.medscape.com/article/313842- overview

45. Conservative measures w/ Nondepolarizing neuromuscular blockers Limit time of paralysis. ‘Sedation vacations’ are used to decrease VAP by getting patient’s off mechanical ventilation sooner. [Kress] Limit time of paralysis. ‘Sedation vacations’ are used to decrease VAP by getting patient’s off mechanical ventilation sooner. [Kress] Maybe this same technique might be helpful with CIM & prolonged neuromuscular blockage? Maybe this same technique might be helpful with CIM & prolonged neuromuscular blockage?

46. Conservative measures w/ Beta II Never forget the Beta II agonists have as side effects: increases both insulin and glucose levels, when combining high dosage Beta II and corticosteroids this could get serious increases both insulin and glucose levels, when combining high dosage Beta II and corticosteroids this could get serious Causes hypokalemia. According to the AHA, inhaled 10-20 mg Albuterol over 15” will shift Potassium into the cell to treat both moderate & severe hyperkalemia [AHA 2005 CPR guidelines pp. 121-122] Causes hypokalemia. According to the AHA, inhaled 10-20 mg Albuterol over 15” will shift Potassium into the cell to treat both moderate & severe hyperkalemia [AHA 2005 CPR guidelines pp. 121-122] Compare this to the AHA recommendations regarding continuous Albuterol TX : 2.5-5mg Q 20 minute x 3 or 10-15 mg/hour Compare this to the AHA recommendations regarding continuous Albuterol TX : 2.5-5mg Q 20 minute x 3 or 10-15 mg/hour

47. Conservative measures w/ Beta II The AHA recommend these drugs as adjuncts to albuterol/IV steroid treatment: A trial of ipratropium bromide as adjunct to albuterol, possibly more that one dose [AHA pp.140] A trial of ipratropium bromide as adjunct to albuterol, possibly more that one dose [AHA pp.140] IV Magnesium Sulfate IV Magnesium Sulfate Leukotriene antagonists by IV has been studied but the AHA wants more research Leukotriene antagonists by IV has been studied but the AHA wants more research

48. Other bronchodilators can have neuromuscular side effects According to the post-marketing experience with Singulair TM a few patients have reported paraesthesia & hypoesthesia—these side effects have not been investigated yet. [drug insert] According to the post-marketing experience with Singulair TM a few patients have reported paraesthesia & hypoesthesia—these side effects have not been investigated yet. [drug insert] Cromolyn Na has peripheral neuritis as a rare side effect [1 in 100,000] Cromolyn Na has peripheral neuritis as a rare side effect [1 in 100,000] Magnesium by IV has respiratory failure due to skeletal muscle paralysis as a side effect Magnesium by IV has respiratory failure due to skeletal muscle paralysis as a side effect

49. references Neil MacIntyre Understanding Ventilator-Induced Diaphragmatic Dysfunction Neil MacIntyre Understanding Ventilator-Induced Diaphragmatic Dysfunction http://www.medscape.com/viewarticle/514526 Deem S.; Intensive-Care-Unit-Acquired Muscle Weakness. Respiratory Care 2006: 51(9): 1024-1041 Deem S.; Intensive-Care-Unit-Acquired Muscle Weakness. Respiratory Care 2006: 51(9): 1024-1041 Dhand, U.; Clinical Approach to the Weak patient in the Intensive Care Unit. Respiratory Care 2006: 51(9): 1024-1041 Dhand, U.; Clinical Approach to the Weak patient in the Intensive Care Unit. Respiratory Care 2006: 51(9): 1024-1041 Boitano, L.J. Management of Airway Clearance in Neuromuscular Disease Respiratory Care August 2006, vol 51 (8) pp. 913-921. Boitano, L.J. Management of Airway Clearance in Neuromuscular Disease Respiratory Care August 2006, vol 51 (8) pp. 913-921.

50. references Nutritional Assessment of patients with respiratory Disease Peters, J.A. & Thomas-Peters, C.D., editors Wilkin’s Clinical Assessment in Respiratory Care 5th edition Elsevier-Mosby Nutritional Assessment of patients with respiratory Disease Peters, J.A. & Thomas-Peters, C.D., editors Wilkin’s Clinical Assessment in Respiratory Care 5th edition Elsevier-Mosby Medline: Rhabdomyolysis http://www.nlm.nih.gov/medlineplus/ency/article/00047 3.htm Medline: Rhabdomyolysis http://www.nlm.nih.gov/medlineplus/ency/article/00047 3.htm http://www.nlm.nih.gov/medlineplus/ency/article/00047 3.htm http://www.nlm.nih.gov/medlineplus/ency/article/00047 3.htm E-medicine: Hypokalemia David Garth, MD, http://www.emedicine.com/emerg/topic273.htm E-medicine: Hypokalemia David Garth, MD, http://www.emedicine.com/emerg/topic273.htm http://www.emedicine.com/emerg/topic273.htm American College of Rheumatology:http://www.rheumatology.org/public/fact sheets/myopathies_new2.asp American College of Rheumatology:http://www.rheumatology.org/public/fact sheets/myopathies_new2.asphttp://www.rheumatology.org/public/fact sheets/myopathies_new2.asphttp://www.rheumatology.org/public/fact sheets/myopathies_new2.asp

51. references Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. New England Journal of Medicine. May 18 2000;342 (20):1471-1477. Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. New England Journal of Medicine. May 18 2000;342 (20):1471-1477. Phua, GC & MacIntyre NR, Inhaled Corticosteriods in COPD, Respiratory Care July 2007, vol 52 #7 Phua, GC & MacIntyre NR, Inhaled Corticosteriods in COPD, Respiratory Care July 2007, vol 52 #7 Critical illness polyneuropathy and myopathy http://www.aic.cuhk.edu.hk/web8/critical_illness_neuropa thy.htm Critical illness polyneuropathy and myopathy http://www.aic.cuhk.edu.hk/web8/critical_illness_neuropa thy.htm http://www.aic.cuhk.edu.hk/web8/critical_illness_neuropa thy.htm http://www.aic.cuhk.edu.hk/web8/critical_illness_neuropa thy.htm CDC pamphlet on CIM and CIPhttp://www.cdc.gov/nchs/data/icd9/icd501a.pdf CDC pamphlet on CIM and CIPhttp://www.cdc.gov/nchs/data/icd9/icd501a.pdfhttp://www.cdc.gov/nchs/data/icd9/icd501a.pdf Merck Manual: Polyneuritis http://www.merck.com/mmhe/sec06/ch095/ch095h.html Merck Manual: Polyneuritis http://www.merck.com/mmhe/sec06/ch095/ch095h.html http://www.merck.com/mmhe/sec06/ch095/ch095h.html eMedicine: Hypermagnesemia by Novello NA; http://www.emedicine.com/EMERG/topic262.htm eMedicine: Hypermagnesemia by Novello NA; http://www.emedicine.com/EMERG/topic262.htm http://www.emedicine.com/EMERG/topic262.htm

52. references Medline Plus: nerve conduction studies http://0- www.nlm.nih.gov.catalog.llu.edu/medlineplus/ency/articl e/003927.htm Medline Plus: nerve conduction studies http://0- www.nlm.nih.gov.catalog.llu.edu/medlineplus/ency/articl e/003927.htmhttp://0- www.nlm.nih.gov.catalog.llu.edu/medlineplus/ency/articl e/003927.htmhttp://0- www.nlm.nih.gov.catalog.llu.edu/medlineplus/ency/articl e/003927.htm AMERICAN THORACIC SOCIETY Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide in Adults and Children1999 AMERICAN THORACIC SOCIETY Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide in Adults and Children1999 http://ajrccm.atsjournals.org/cgi/content/full/160/6/2104 ?ijkey=43b2934ac6dfa8de010ee9b85d910dbfed797135& keytype2=tf_ipsecsha http://ajrccm.atsjournals.org/cgi/content/full/160/6/2104 ?ijkey=43b2934ac6dfa8de010ee9b85d910dbfed797135& keytype2=tf_ipsecsha http://ajrccm.atsjournals.org/cgi/content/full/160/6/2104 ?ijkey=43b2934ac6dfa8de010ee9b85d910dbfed797135& keytype2=tf_ipsecsha http://ajrccm.atsjournals.org/cgi/content/full/160/6/2104 ?ijkey=43b2934ac6dfa8de010ee9b85d910dbfed797135& keytype2=tf_ipsecsha

53. references V Segredo, JE Caldwell, et al. Persistent paralysis in critically ill patients after long-term administration of vecuronium. NEJ Vol 327:524-528 #8 August 20, 1992 http://content.nejm.org/cgi/content/abstract/327/8/524? ijkey=8e4db6aea6531d7ea4f0d9c3eb1a90f706fb333f&ke ytype2=tf_ipsecsha V Segredo, JE Caldwell, et al. Persistent paralysis in critically ill patients after long-term administration of vecuronium. NEJ Vol 327:524-528 #8 August 20, 1992 http://content.nejm.org/cgi/content/abstract/327/8/524? ijkey=8e4db6aea6531d7ea4f0d9c3eb1a90f706fb333f&ke ytype2=tf_ipsecsha http://content.nejm.org/cgi/content/abstract/327/8/524? ijkey=8e4db6aea6531d7ea4f0d9c3eb1a90f706fb333f&ke ytype2=tf_ipsecsha http://content.nejm.org/cgi/content/abstract/327/8/524? ijkey=8e4db6aea6531d7ea4f0d9c3eb1a90f706fb333f&ke ytype2=tf_ipsecsha E-Medicine/ orticosteroid-Induced Myopathy. Steve S Lim, MD, & Patrick M Foye, MD, E-Medicine/ orticosteroid-Induced Myopathy. Steve S Lim, MD, & Patrick M Foye, MD, http://emedicine.medscape.com/article/313842-overview http://emedicine.medscape.com/article/313842-overview http://emedicine.medscape.com/article/313842-overview Long-term outcome in patients with critical illness myopathy or neuropathy: the Italian multicentre CRIMYNE study B Guarneri, G Bertolini, N Latronico J Neurol Neurosurg Psychiatry 2008;79:838-841 Long-term outcome in patients with critical illness myopathy or neuropathy: the Italian multicentre CRIMYNE study B Guarneri, G Bertolini, N Latronico J Neurol Neurosurg Psychiatry 2008;79:838-841