TSRC 37TSRC 37thth Annual Convention Annual ConventionCritical illness Myopathy Critical illness Myopathy

& & Critical illness Critical illness

PolyneuropathyPolyneuropathy

By Elizabeth Kelley Buzbee AAS, RRT, By Elizabeth Kelley Buzbee AAS, RRT, NPSNPS

Lone Star System- Kingwood [formerly known as Lone Star System- Kingwood [formerly known as Kingwood College]Kingwood College]

Failure to wean due to muscle Failure to wean due to muscle weaknessweakness

The effect of invasive mechanical ventilation on the The effect of invasive mechanical ventilation on the patient’s ventilatory skeletal muscles is a well-patient’s ventilatory skeletal muscles is a well-known yet fairly complex problem. known yet fairly complex problem.

Full ventilatory support can trigger muscle atrophy Full ventilatory support can trigger muscle atrophy within 72 hours in adults. According to MacIntyre, within 72 hours in adults. According to MacIntyre, both muscle mass and cross-section of muscle fibers both muscle mass and cross-section of muscle fibers are affected. are affected. [MacIntyre pp. 1[MacIntyre pp. 1http://www.medscape.com/viewarticle/514526] ]

“ “There is….. evidence of oxidative stress and There is….. evidence of oxidative stress and protein breakdown in the musclesprotein breakdown in the muscles.” .” [MacIntyre pp. 1][MacIntyre pp. 1]

When a patient’s FRC is raised above normal by PPV, When a patient’s FRC is raised above normal by PPV, the effect on resting muscle length results in a the effect on resting muscle length results in a decrease in muscle strength. decrease in muscle strength. [MacIntyre pp. 1][MacIntyre pp. 1]

Alterations in the blood flow to the ventilatory Alterations in the blood flow to the ventilatory muscles secondary to PPV just adds to the problem. muscles secondary to PPV just adds to the problem. [[MacIntyre pp. 1]MacIntyre pp. 1]

Not only is muscle strength affected, we will see a Not only is muscle strength affected, we will see a decrease in muscle endurance. decrease in muscle endurance. [MacIntyre pp. 1][MacIntyre pp. 1]

Other problems are more Other problems are more subtle subtle

malnutrition & electrolyte imbalances:malnutrition & electrolyte imbalances: The effects of malnutrition on the pulmonary system are The effects of malnutrition on the pulmonary system are

distinct and well known.distinct and well known. Patient’s who cannot take oral nutrition may be on IV Patient’s who cannot take oral nutrition may be on IV

glucose, which is fine for a day or so, but TPN with its glucose, which is fine for a day or so, but TPN with its more complete nutritional support is needed to keep more complete nutritional support is needed to keep metabolism going.metabolism going.

Carbohydrates are needed for both the diaphragm Carbohydrates are needed for both the diaphragm and the myocardium and the myocardium [Peters pp. 350][Peters pp. 350]

The effect of electrolyte imbalances on the myocardium The effect of electrolyte imbalances on the myocardium is well-known but potassium levels can also affect is well-known but potassium levels can also affect skeletal muscle action of the chest and abdominal skeletal muscle action of the chest and abdominal muscles.muscles. Hypokalemia can cause muscle weakness even Hypokalemia can cause muscle weakness even

paralysis paralysis [Garth][Garth] while hyperkalemia also results in muscle weakness while hyperkalemia also results in muscle weakness

and flaccid paralysisand flaccid paralysis serum magnesium levels of 8.0-10.0 mEq/L are serum magnesium levels of 8.0-10.0 mEq/L are

associated with flaccid skeletal muscle paralysis. associated with flaccid skeletal muscle paralysis. [Novello ][Novello ]

The new threat in the The new threat in the ICUICU

There are new problems discovered in the ICU There are new problems discovered in the ICU that result in various degrees of muscle that result in various degrees of muscle weakness--even paralysis-- that can keep a weakness--even paralysis-- that can keep a person from weaning off mechanical ventilation person from weaning off mechanical ventilation [Dhand pp. 1025][Dhand pp. 1025]

But is this a new problem?But is this a new problem? A review of the A review of the literature shows that as early as the 1970s, a literature shows that as early as the 1970s, a small number of severe asthmatic patients who small number of severe asthmatic patients who were intubated, paralyzed and ventilated had were intubated, paralyzed and ventilated had significant, generalized muscle weakness.significant, generalized muscle weakness. Critical illness polyneuropathyCritical illness polyneuropathy Critical illness myopathyCritical illness myopathy Prolonged neuromuscular blockageProlonged neuromuscular blockage

Occurrence of CIP, CIM or a Occurrence of CIP, CIM or a combination of the twocombination of the two

as many as 30-50% of patients with as many as 30-50% of patients with critical illness. critical illness. [Dhand pp. 1026][Dhand pp. 1026]

Another study [n=206] found 25% of Another study [n=206] found 25% of critical care patients who had been critical care patients who had been mechanically ventilated for more than 7 mechanically ventilated for more than 7 days had a degree of muscle weakness. days had a degree of muscle weakness. This study included only persons who This study included only persons who were awake and responsive were awake and responsive [Deems pp. [Deems pp. 1043]1043]

Critical illness myopathyCritical illness myopathy

Critical illness myopathyCritical illness myopathy

According to the According to the American College of American College of RheumatologyRheumatology, myopathy is a disease , myopathy is a disease of the muscles. The actual of the muscles. The actual manifestation of the muscle disease manifestation of the muscle disease varies widely based on etiology and the varies widely based on etiology and the location of the defect. location of the defect.

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

Risk factors for Critical Risk factors for Critical illness myopathyillness myopathy

Persons who have received high Persons who have received high levels of corticosteroids & levels of corticosteroids & neuromuscular blocking agents neuromuscular blocking agents

for diseases such as severe asthma, for diseases such as severe asthma, COPD exacerbation, sepsis, ARDS COPD exacerbation, sepsis, ARDS and s/p organ transplants. and s/p organ transplants. [Dhand pp. 1036][Dhand pp. 1036]

S/S of Critical illness S/S of Critical illness myopathymyopathy

Inspection and interview of the Inspection and interview of the patientpatient

There also seem to be is little in the There also seem to be is little in the inspection and interview to differentiate inspection and interview to differentiate between critical illness myopathy and between critical illness myopathy and critical illness polyneuropathy. critical illness polyneuropathy.

The patient will c/o weakness in both The patient will c/o weakness in both situations.situations.

S/S of Critical illness S/S of Critical illness myopathymyopathy

Serum Creatine KinaseSerum Creatine Kinase a product of muscle damage. Need to a product of muscle damage. Need to

differentiate between myocardial CK and differentiate between myocardial CK and skeletal muscle CK. skeletal muscle CK. [Egan’s pp. 351][Egan’s pp. 351]

““Normal levels of serum creatine kinase are Normal levels of serum creatine kinase are usually between 25 and 200 U/L. This test is usually between 25 and 200 U/L. This test is not specific for the not specific for the typetype of CK that is of CK that is elevated.” elevated.” [[http://en.wikipedia.org/wiki/Creatine_kinase]]

Serum creatine kinase may be 10-100 x Serum creatine kinase may be 10-100 x higher than normal in CIM in the first 3-4 higher than normal in CIM in the first 3-4 days-- then stabilize after 10 days. days-- then stabilize after 10 days. [Dhand pp. [Dhand pp. 1028]1028]

S/S of Critical illness S/S of Critical illness myopathymyopathy

EMG: the electromyogramEMG: the electromyogram . There are two basic techniques:. There are two basic techniques:

One can study a specific muscle fiber’s reaction to the One can study a specific muscle fiber’s reaction to the insertion of a needle electrode in a particular muscle insertion of a needle electrode in a particular muscle fiber. fiber.

A less-invasive procedure uses a surface electrode to A less-invasive procedure uses a surface electrode to monitor the general picture of muscle activation. During monitor the general picture of muscle activation. During this study the patient has auditory or visual stimuli to this study the patient has auditory or visual stimuli to help them know when they are activating the muscle. help them know when they are activating the muscle. Again the action potential is measuredAgain the action potential is measured

http://en.wikipedia.org/wiki/Electromyography It is possible to perform an EMG of the phrenic nerve It is possible to perform an EMG of the phrenic nerve

by placing the percutaneous electrode onto the neck by placing the percutaneous electrode onto the neck at the supraclavicular fossa and measurements will at the supraclavicular fossa and measurements will be made at two spots along the anterior rib cage, be made at two spots along the anterior rib cage,

but the presence of a central line in either neck will but the presence of a central line in either neck will make this EMG impossible. make this EMG impossible. [Dhand pp. 1031-1032][Dhand pp. 1031-1032]

S/S of Critical illness S/S of Critical illness myopathymyopathyEMG resultsEMG results

In myopathic disorders there will In myopathic disorders there will be decreases in duration of the be decreases in duration of the action potential, action potential,

and in the ratio of area to and in the ratio of area to amplitude and in the number of amplitude and in the number of motor unit in the muscles [worse motor unit in the muscles [worse cases only] cases only] [[http://en.wikipedia.org/wiki/Amplitude]]

S/S of Critical illness S/S of Critical illness myopathymyopathy

Nerve conduction studyNerve conduction study In the nerve conduction study the patient is In the nerve conduction study the patient is

given an electrical shock at various spots given an electrical shock at various spots along a nerve. along a nerve.

Among other measurements, the Among other measurements, the velocityvelocity of of the nerve conduction is measured at the nerve conduction is measured at different points, as is the intensity of the different points, as is the intensity of the response [response [amplitudeamplitude.] The tester will study .] The tester will study both the motor and the sensory nerve both the motor and the sensory nerve conduction. conduction. http://en.wikipedia.org/wiki/Nerve_conduction_study

In the case of CIM, there should be no real In the case of CIM, there should be no real problems with conductionproblems with conduction

S/S of Critical illness S/S of Critical illness myopathymyopathy

Problems w/ Nerve conduction studiesProblems w/ Nerve conduction studiesin the ICU: in the ICU: the patient’s skin temperature will the patient’s skin temperature will

change the speed of conduction; cool change the speed of conduction; cool bodies result in slow conductionbodies result in slow conduction

and the presence of pacemakers & and the presence of pacemakers & indwelling defibrillators can make for indwelling defibrillators can make for difficulties [difficulties [MedlinePlus: nerve conduction studies]MedlinePlus: nerve conduction studies]

Picture of NCS: Picture of NCS: http://0-www.nlm.nih.gov.catalog.llu.edu/medlineplus/ency/imagepages/9743.htm

S/S of Critical illness S/S of Critical illness myopathymyopathy

What are we left with?What are we left with?

Muscle and nerve biopsyMuscle and nerve biopsy Both muscle and nerve biopsy Both muscle and nerve biopsy

can differentiate between CIP can differentiate between CIP and CIM and even combinations and CIM and even combinations of both disorders. of both disorders. [Dhand pp.1033][Dhand pp.1033]

Critical illness Critical illness polyneuropathypolyneuropathy

Critical illness Critical illness polyneuropathypolyneuropathy

The Merck manual describes The Merck manual describes polyneuropathy as “the simultaneous polyneuropathy as “the simultaneous malfunction of many peripheral malfunction of many peripheral nerves throughout the body.”nerves throughout the body.”

In CIP, with biopsy, one sees that the In CIP, with biopsy, one sees that the patient develops both motor and patient develops both motor and sensory degeneration without sensory degeneration without inflammation. inflammation. [Dhand pp. 1033][Dhand pp. 1033]

Risk factors for Risk factors for polyneuropathypolyneuropathy

““Poor control of blood sugar levels in Poor control of blood sugar levels in diabetes causes several forms of diabetes causes several forms of polyneuropathy, collectively referred to as polyneuropathy, collectively referred to as diabetic neuropathy.”diabetic neuropathy.” [Merck Manual][Merck Manual]

Diphtheria toxins, autoimmune reaction, Diphtheria toxins, autoimmune reaction, heavy metals such as lead and mercury and heavy metals such as lead and mercury and CO poisoning can all lead to polyneuropathy. CO poisoning can all lead to polyneuropathy.

The drugs include the anticonvulsant, The drugs include the anticonvulsant, Dilantin, Dilantin, some antibiotics (such as nitrofurantoin and some antibiotics (such as nitrofurantoin and sulfonamides), some chemotherapy drugs sulfonamides), some chemotherapy drugs and some sedatives such as barbital. and some sedatives such as barbital. [Merck [Merck Manual]Manual]

Risk factors for Critical Risk factors for Critical illness polyneuropathyillness polyneuropathy

History of sepsis, trauma, burn History of sepsis, trauma, burn followed by organ failure, septic followed by organ failure, septic encephalopathy. encephalopathy. [Dhand pp. 1033.][Dhand pp. 1033.]

in addition, according to the CDC, CIP in addition, according to the CDC, CIP is associated with a recent history of is associated with a recent history of SIRV [septic inflammatory response SIRV [septic inflammatory response syndrome. [syndrome. [CDCCDC] ] http://www.cdc.gov/nchs/data/icd9/icd501a.pdf

S/S critical illness S/S critical illness polyneuropathypolyneuropathy

On inspection: On inspection: Because cranial nerves are generally Because cranial nerves are generally

unaffected in CIP, the patient’s facial unaffected in CIP, the patient’s facial grimace and limb movement on grimace and limb movement on painful stimulation may be strikingly painful stimulation may be strikingly different. different. [CDC][CDC]

A muscle biopsy would show A muscle biopsy would show neuropathic changes. neuropathic changes. [Dhand pp. 1034.][Dhand pp. 1034.]

S/S critical illness S/S critical illness polyneuropathypolyneuropathy

He have a normal He have a normal Creatine kinaseCreatine kinase. . [Dhand pp. 1034.][Dhand pp. 1034.]

he would have a reduction he would have a reduction in both motor & sensory in both motor & sensory nerve conduction. nerve conduction. [Dhand pp. 1029.][Dhand pp. 1029.]

S/S critical illness S/S critical illness polyneuropathypolyneuropathy

EMG resultsEMG results the EMG showed action the EMG showed action

potentials twice normal with potentials twice normal with increased fibers per motor unit increased fibers per motor unit and an increase in duration of and an increase in duration of the action potentialthe action potential. . [[http://en.wikipedia.org/wiki/Amplitude]]

Prolonged neuromuscular Prolonged neuromuscular blockageblockage

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

Prolonged Prolonged neuromuscular blockageneuromuscular blockage

Prolonged neuromuscular Prolonged neuromuscular blockageblockage

Prolonged neuromuscular blockage with Prolonged neuromuscular blockage with nondepolarizing blocking agents results in nondepolarizing blocking agents results in metabolites.metabolites.

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

Risk factors for Prolonged Risk factors for Prolonged neuromuscular blockageneuromuscular blockage

Patients at increased risk seem to be Patients at increased risk seem to be those with: those with:

hepatic dysfunctionhepatic dysfunction renal failurerenal failure acidosis acidosis or hypermagnesemia or hypermagnesemia [Dhand pp. 1036][Dhand pp. 1036]

Differential DXDifferential DX

Differential DXDifferential DX

Polyneuropathies such as Polyneuropathies such as Guillian Barre Guillian Barre syndromesyndrome can be triggered by infection, can be triggered by infection,

while exacerbations of while exacerbations of myasthenia gravismyasthenia gravis [[MGMG crisiscrisis]] can be triggered by stress, can be triggered by stress, certain medications and illness. certain medications and illness.

Spinal cord infarction is a complication of Spinal cord infarction is a complication of aortic surgery aortic surgery [Dhand pp. 1026.][Dhand pp. 1026.]

myotonic dystrophymyotonic dystrophy may have been may have been undiagnosedundiagnosed

Differential DXDifferential DX

Guillian BarreGuillian Barre.. There are no … antibodies in the There are no … antibodies in the

serum of patients with critical illness serum of patients with critical illness polyneuropathy as would be seen polyneuropathy as would be seen with Guillian Barre. with Guillian Barre. http://jnnp.bmj.com/cgi/content/extract/68/3/397

Differential DXDifferential DX

myasthenia gravis.myasthenia gravis. Patients have increasing muscle Patients have increasing muscle

weakness with repetitive motionsweakness with repetitive motions they also antibodies against they also antibodies against

acetylcholine receptors acetylcholine receptors tendency to have a degree of facial tendency to have a degree of facial

paralysis [inability to protect the paralysis [inability to protect the airway],airway],

a transient improvement when given a transient improvement when given cholinesterase inhibitors. cholinesterase inhibitors. [Egan’s pp. 576][Egan’s pp. 576]

Differential DXDifferential DX

Spinal cord infarctionSpinal cord infarction Comes on suddenly and Comes on suddenly and

catostrophically with 80% c/o severe catostrophically with 80% c/o severe painpain

http://www.emedicine.com/NEURO/topic348.htm

Differential DXDifferential DX

myotonic dystrophymyotonic dystrophy Persons with Persons with myotonic dystrophymyotonic dystrophy

have increased sensitivities not have increased sensitivities not only to paralytic agents, but to only to paralytic agents, but to CNS depressants. CNS depressants. [Egan’s pp. 576][Egan’s pp. 576]

Treatment?Treatment?

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

We need to stop killing black We need to stop killing black widow spiders with a sledge widow spiders with a sledge

hammer.hammer.

May just tear up the houseMay just tear up the house

Conservative measures w/ Conservative measures w/ steroidssteroids

According to the According to the American Heart Association American Heart Association 2005 CPR guidelines2005 CPR guidelines, severe asthma needs to be , severe asthma needs to be treated with systemic steroids rather than topical: treated with systemic steroids rather than topical: but maybe we need more studies to be done but maybe we need more studies to be done

with inhaled dosages so that the systemic side with inhaled dosages so that the systemic side effects such as myopathy can be minimized?effects such as myopathy can be minimized?

In these studies, how are these patients given In these studies, how are these patients given inhaled steroids? [mixed with Beta II or alone? inhaled steroids? [mixed with Beta II or alone? SVN or MDI, DPI? ]SVN or MDI, DPI? ]

Exactly what are the links between steroid-Exactly what are the links between steroid-induced diabetes and neuropathy: how much induced diabetes and neuropathy: how much steroid is too much?steroid is too much?

Conservative measures w/ Conservative measures w/ steroid TXsteroid TX

could we use offline measurements for could we use offline measurements for intubated patients?intubated patients?

Research is on going on the question of using Research is on going on the question of using exhaled nitric oxide monitors to fine-tune the level exhaled nitric oxide monitors to fine-tune the level of systemic steroids in the acute asthmatic. of systemic steroids in the acute asthmatic. [Phua pp. 857][Phua pp. 857]

Offline measurement of FEOffline measurement of FENONO has been compared has been compared favorably with online modes favorably with online modes

One UK single-blind study over a period of 8 months One UK single-blind study over a period of 8 months [[nn =116] showed no clinically significant =116] showed no clinically significant improvement in controlling patient’s steroid dosages improvement in controlling patient’s steroid dosages by monitoring FENO by monitoring FENO http://ajrccm.atsjournals.org/cgi/content/abstract/17http://ajrccm.atsjournals.org/cgi/content/abstract/176/3/2316/3/231

Conservative measures w/ Conservative measures w/ Nondepolarizing Nondepolarizing

neuromuscular blockersneuromuscular blockers

Limit time of paralysisLimit time of paralysis. ‘Sedation . ‘Sedation vacations’ are used to decrease VAP vacations’ are used to decrease VAP by getting patient’s off mechanical by getting patient’s off mechanical ventilation sooner. ventilation sooner. [Kress][Kress]

Maybe this same technique might be Maybe this same technique might be helpful with CIM & prolonged helpful with CIM & prolonged neuromuscular blockage?neuromuscular blockage?

Conservative measures w/ Conservative measures w/ Beta IIBeta II

Never forget the Beta II agonists have as side effects:Never forget the Beta II agonists have as side effects: increases both increases both insulininsulin and and glucoseglucose levels, levels,

when combining high dosage Beta II and when combining high dosage Beta II and corticosteroids this could get seriouscorticosteroids this could get serious

Causes hypokalemiaCauses hypokalemia. According to the AHA, . According to the AHA, inhaled 10-20 mg Albuterol over 15” will shift inhaled 10-20 mg Albuterol over 15” will shift Potassium into the cell to treat both moderate & Potassium into the cell to treat both moderate & severe hyperkalemia severe hyperkalemia [AHA 2005 CPR guidelines pp. 121-[AHA 2005 CPR guidelines pp. 121-122] 122]

Compare this to the AHA recommendations regarding Compare this to the AHA recommendations regarding continuous Albuterol TX : 2.5-5mg Q 20 minute x 3 or continuous Albuterol TX : 2.5-5mg Q 20 minute x 3 or 10-15 mg/hour 10-15 mg/hour

Conservative measures w/ Conservative measures w/ Beta IIBeta II

The AHA recommend these drugs as The AHA recommend these drugs as adjuncts to albuterol/IV steroid treatment:adjuncts to albuterol/IV steroid treatment: A trial of ipratropium bromide as adjunct A trial of ipratropium bromide as adjunct

to albuterol, possibly more that one to albuterol, possibly more that one dose dose [AHA pp.140][AHA pp.140]

IV Magnesium SulfateIV Magnesium Sulfate Leukotriene antagonists by IV has been Leukotriene antagonists by IV has been

studied but the AHA wants more studied but the AHA wants more researchresearch

Other bronchodilators can Other bronchodilators can have neuromuscular side have neuromuscular side

effects effects According to the post-marketing experience According to the post-marketing experience

with with Singulair Singulair TMTM a few patients have a few patients have reported paraesthesia & hypoesthesia—reported paraesthesia & hypoesthesia—these side effects have not been investigated these side effects have not been investigated yet. yet. [drug insert][drug insert]

Cromolyn NaCromolyn Na has peripheral neuritis as a has peripheral neuritis as a rare side effect [1 in 100,000]rare side effect [1 in 100,000]

Magnesium Magnesium by IV has respiratory failure due by IV has respiratory failure due to skeletal muscle paralysis as a side effect to skeletal muscle paralysis as a side effect

referencesreferences

Neil MacIntyre Neil MacIntyre Understanding Ventilator-Induced Understanding Ventilator-Induced Diaphragmatic DysfunctionDiaphragmatic Dysfunction    http://www.medscape.com/viewarticle/514526http://www.medscape.com/viewarticle/514526

Deem S.; Deem S.; Intensive-Care-Unit-Acquired Muscle WeaknessIntensive-Care-Unit-Acquired Muscle Weakness. . Respiratory Care 2006: 51(9): 1024-1041Respiratory Care 2006: 51(9): 1024-1041

Dhand, U.; Dhand, U.; Clinical Approach to the Weak patient in the Clinical Approach to the Weak patient in the Intensive Care UnitIntensive Care Unit. Respiratory Care 2006: 51(9): 1024-. Respiratory Care 2006: 51(9): 1024-1041 1041

Boitano, L.J. Boitano, L.J. Management of Airway Clearance in Management of Airway Clearance in Neuromuscular DiseaseNeuromuscular Disease Respiratory Care August 2006, vol Respiratory Care August 2006, vol 51 (8) pp. 913-921.51 (8) pp. 913-921.

referencesreferences Nutritional Assessment of patients with Nutritional Assessment of patients with

respiratory Disease Peters, J.A. & Thomas-Peters, respiratory Disease Peters, J.A. & Thomas-Peters, C.D., editors C.D., editors Wilkin’s Clinical Assessment in Wilkin’s Clinical Assessment in Respiratory CareRespiratory Care 5th edition Elsevier-Mosby 5th edition Elsevier-Mosby

Medline: Rhabdomyolysis Medline: Rhabdomyolysis http://www.nlm.nih.gov/medlineplus/ency/article/http://www.nlm.nih.gov/medlineplus/ency/article/000473.htm000473.htm

E-medicine: Hypokalemia David Garth, MD, E-medicine: Hypokalemia David Garth, MD, http://www.emedicine.com/emerg/topic273.htmhttp://www.emedicine.com/emerg/topic273.htm

American College of American College of Rheumatology:http://www.rheumatology.org/publiRheumatology:http://www.rheumatology.org/public/factsheets/myopathies_new2.aspc/factsheets/myopathies_new2.asp

referencesreferences Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily

interruption of sedative infusions in critically ill patients interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. New England Journal undergoing mechanical ventilation. New England Journal of Medicineof Medicine.. May 18 2000;342 (20):1471-1477. May 18 2000;342 (20):1471-1477.

Phua, GC & MacIntyre NR, Inhaled Corticosteriods in COPDPhua, GC & MacIntyre NR, Inhaled Corticosteriods in COPD,, Respiratory Care July 2007 , vol 52 #7Respiratory Care July 2007 , vol 52 #7

Critical illness polyneuropathy and myopathy Critical illness polyneuropathy and myopathy http://www.aic.cuhk.edu.hk/web8/critical_illness_neuhttp://www.aic.cuhk.edu.hk/web8/critical_illness_neuropathy.htmropathy.htm

CDC pamphlet on CIM and CDC pamphlet on CIM and CIPhttp://www.cdc.gov/nchs/data/icd9/icd501a.pdfCIPhttp://www.cdc.gov/nchs/data/icd9/icd501a.pdf

Merck Manual: Polyneuritis Merck Manual: Polyneuritis http://www.merck.com/mmhe/sec06/ch095/ch095h.htmlhttp://www.merck.com/mmhe/sec06/ch095/ch095h.html

eMedicine: Hypermagnesemia by Novello NA; eMedicine: Hypermagnesemia by Novello NA; http://www.emedicine.com/EMERG/topic262.htmhttp://www.emedicine.com/EMERG/topic262.htm

  

referencesreferences Medline Plus: nerve conduction studies http://0-Medline Plus: nerve conduction studies http://0-

www.nlm.nih.gov.catalog.llu.edu/medlineplus/encwww.nlm.nih.gov.catalog.llu.edu/medlineplus/ency/article/003927.htmy/article/003927.htm

AMERICAN THORACIC SOCIETYAMERICAN THORACIC SOCIETYRecommendations for Standardized Procedures Recommendations for Standardized Procedures for the Online and Offline Measurement of for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide in Adults and Children1999Nitric Oxide in Adults and Children1999

http://ajrccm.atsjournals.org/cgi/content/full/http://ajrccm.atsjournals.org/cgi/content/full/160/6/2104?160/6/2104?ijkey=43b2934ac6dfa8de010ee9b85d910dbfed79ijkey=43b2934ac6dfa8de010ee9b85d910dbfed797135&keytype2=tf_ipsecsha7135&keytype2=tf_ipsecsha

  

referencesreferences V Segredo, JE Caldwell, et al. Persistent paralysis V Segredo, JE Caldwell, et al. Persistent paralysis

in critically ill patients after long-term in critically ill patients after long-term administration of vecuronium. NEJ Vol 327:524-administration of vecuronium. NEJ Vol 327:524-528 #8 August 20, 1992 528 #8 August 20, 1992 http://content.nejm.org/cgi/content/abstract/327/http://content.nejm.org/cgi/content/abstract/327/8/524?8/524?ijkey=8e4db6aea6531d7ea4f0d9c3eb1a90f706fbijkey=8e4db6aea6531d7ea4f0d9c3eb1a90f706fb333f&keytype2=tf_ipsecsha333f&keytype2=tf_ipsecsha