#202: Vertebroplasty and Kyphoplasty for Vertebral Compression Fractures

Fast Fact and Concept #202

Vertebroplasty and Kyphoplasty for vertebral compression fractures

Marcin Chwistek MD and Rohtesh Mehta MD

Background Vertebral compression fractures (VCFs) occur in up to 20% of patients above the age of 50, mostly due to osteoporosis. Malignant VCFs are the result of osteolytic lesions from multiple myeloma or metastatic carcinoma and occur in up to 30% of patients with bone metastases. VCFs can cause significant acute and long-term pain, can compromise pulmonary function, and impair activities of daily living and mobility. Vertebroplasty (VP) and balloon Kyphoplasty (BKP) are minimally invasive surgical techniques used for treatment of both osteoporotic and malignant VCFs.

Technique VP involves percutaneous injection of cement (polymethylmethacrylate - PMMA) into a fractured vertebral body. BKP involves inserting an inflatable balloon in the vertebral body first – to attempt to elevate the vertebral end plates – with subsequent insertion of PMMA. Both are outpatient procedures, done under conscious sedation and local anesthesia, with fluoroscopic guidance. Some clinicians will augment multiple levels at once.

Patient Selection Careful correlation of a patient’s symptoms with the level of the fracture is important, as not all fractures are painful, and alternative causes of pain need to be considered. Patients with painful acute or chronic VCFs are appropriate for interventional consideration, although outcomes are slightly better in the acute setting. BKP is substantially more expensive than VP, and has not demonstrated superiority to VP in any trial. Some practitioners empirically favor BKP in case of significant kyphosis (deformity more than 20°) or when VP is difficult due to posterior vertebral cortex involvement, which makes cement extravasation more likely. VP, on the other hand, is favored when insertion of balloon device is technically difficult due to severe vertebral collapse (greater than 65% reduction in vertebral height) or if the fracture is more than 3 months old, in which case elevation of the endplate is unlikely.

Relative contraindications include the presence of any neurologic damage related to the fracture, fractures with a burst component (where bone fragments extend into the spinal canal), systemic or local infection, uncorrected hypercoagulable state, and severe cardiopulmonary disease.

Complications

· Cement Extravasation is more common in VP (up to 40%, depending on the series) than in BKP (up to 13%). Cement leaks are rarely symptomatic.

· Pulmonary or neurologic emboli can occur from displaced bone marrow in less than1% of cases.

· Infectious complications such as pyogenic spondylitis and osteomyelitis are very rare.

Outcomes There are no completed trials comparing VP and BKP. Case series and uncontrolled trials have generally shown both procedures to have similar efficacy with regard to acute pain relief, leading to greater mobilization. Pain reduction occurs in 70-90% of cases with VP and in 67-100% in BKP; often more than a 5 point drop (on a 0-10 scale) in the immediate postoperative period is observed in responders, along with significant decrease in analgesic use at 1 month. Pain relief seems to be better in patients with osteoporotic VCFs as compared to those with malignant fractures, however studies in cancer patients have shown an approximately 50-60% reduction in pain following intervention. BKP is reported to contribute to better long-term pain control (more than 2 years) than VP (73% vs. 41%, respectively); however, these data are not from a head-to-head comparison. Both BKP and VP lead to partial vertebral height restoration in selected patients.

Summary VP and KP are effective analgesic interventions for painful VCFs in many patients, and can be particularly helpful for patients who poorly tolerate opioids and other analgesics. Although the precise indications and contraindications are still evolving, these minimally invasive procedures should be considered as a part of a multidisciplinary approach to patients with painful VCFs. Patients taking opioids should be evaluated carefully after VP or BKP, as they may need dose reductions.

References:

1. Diamond TH, Bryant C, Browne L et al., Clinical outcomes after acute osteoporotic vertebral fractures: a 2-year non-randomised trial comparing percutaneous vertebroplasty with conservative therapy, Med J Aust. 2006; 184:113–117.
2. Hulme PA, Krebs J., Ferguson SJ et al., Vertebroplasty and kyphoplasty: a systematic review of 69 clinical studies. Spine. 2006; 31:1983–2001.
3. Taylor RS, Taylor RJ, Fritzell P. Balloon kyphoplasty in the management of vertebral compression fractures: an updated systematic review and meta-analysis. Spine. 2006; 31(23):2747-55.
4. Mueller CW, Berlemann U. Kyphoplasty: chances and limits. Neurol India. 2005; 53(4): 451-7.
5. Hadjipavlou AG, Tzermiadianos MN, Katonis PG, Szpalski M. Percutaneous vertebroplasty and balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures and osteolytic tumours. J Bone Joint Surg Br. 2005; 87(12): 1595-604.
6. Fourney DR, Schomer DF, Nader R, et al. Percutaneous vertebroplasty and kyphoplasty for painful vertebral body fractures in cancer patients. J Neurosurg. 2003; 98(1 Suppl): 21-30.
7. Pateder DB, Khanna AJ, Lieberman IH. Vertebroplasty and kyphoplasty for the management of osteoporotic vertebral compression fractures. Orthop Clin North Am. 2007; 38(3):409-18.
8. Melton LJ 3rd, Kallmes DF. Epidemiology of vertebral fractures: implications for vertebral augmentation. Acad Radiol. 2006; 13(5):538-45.
9. Lieberman I, Reinhardt MK. Vertebroplasty and kyphoplasty for osteolytic vertebral collapse. Clin Orthop Relat Res. 2003; 415(Suppl):S176-86.
10. Dudeney S, Lieberman IH, Reinhardt MK, Hussein M. Kyphoplasty in the treatment of osteolytic vertebral compression fractures as a result of multiple myeloma. J Clin Oncol. 2002; 20(9):2382-7.
11. Khanna AJ, Reinhardt MK, Togawa D, Lieberman IH. Functional outcomes of kyphoplasty for the treatment of osteoporotic and osteolytic vertebral compression fractures. Osteoporos Int. 2006; 17(6):817-26.
12. Ecker RD, Endo T, Wetjen NM, Krauss WE. Diagnosis and treatment of vertebral column metastases. Mayo Clin Proc. 2005; 80(9):1177-86.
13. Jensen ME, McGraw JK, Cardella JF, Hirsch JA. Position statement on percutaneous vertebral augmentation: a consensus statement developed by the American Society of Interventional and Therapeutic Neuroradiology, Society of Interventional Radiology, American Association of Neurological Surgeons/Congress of Neurological Surgeons, and American Society of Spine Radiology. Am J Neuroradiol. 2007; 28(8):1439-43.

This Fast Fact is available at EPERC here.  

#201: Palliative care for patients with Huntington's disease

FAST FACT AND CONCEPT #201

Palliative Care for Patients with Huntington’s Disease

Sean Marks MD, Serena Hung MD, and Drew Rosielle MD

 

Background   Huntington’s disease (HD) is an incurable neurodegenerative disorder inherited in an autosomal dominant fashion.  It is characterized by progressive movement disorders, psychiatric manifestations, behavioral abnormalities, and cognitive impairment.  This Fast Fact will focus on supportive and terminal care for patients with HD and their families. 

 

Natural History and Prognosis 

·   Symptom onset is usually between 33 and 44 years; subtle cognitive and motor changes may precede diagnosis by many years. Mean duration of illness from onset to death is 15-20 years with average age of death of 60 years; there are no proven therapies which slow the progression of HD.

·   Patients show signs of progressive dementia and become unable to walk, talk, take in nutrition, and care for themselves.  Life threatening complications may result from aspiration, chronic infections, poor nutrition, falls, or cardiovascular disease.

·   ~1/3 of all patients with HD are institutionalized in long-term care facilities.

 

Impact on Families   HD often begins during a time when family life is most complex and therefore most disruptive to the family structure (e.g. child-rearing, career development).  Children can be particularly affected: distress is aggravated by concerns about their own genetic susceptibility, and as many as 40% of children of HD patients describe HD as splitting their family apart.  Careful assessments of familial coping and psychosocial needs are an integral part of ongoing care for the HD patient.

 

Common Symptoms and Supportive Care    Patients are best served by an interdisciplinary team familiar with caring for patients with HD.

·   Motor Manifestations. Abnormal involuntary movements include: chorea, dystonia, rigidity, bradykinesia, tremor, and myoclonus; other motor manifestations include gait and balance problems leading to frequent falls, slurred speech and swallowing difficulties

o  First-line strategies are non-pharmacologic and include gait/balance training, speech therapy, and orthotics and leg weights to assist with upright posture. 

o  Chorea is the most frequently targeted symptom for pharmacologic therapy.  Tetrabenazine (a dopamine depleting agent) has been shown to reduce chorea in a well-designed placebo controlled trial; it is undergoing approval in the US.  Haloperidol and other antipsychotics are also used for chorea, although trials evaluating their effectiveness have shown mixed results.

·   Psychiatric manifestations are present in over half of HD patients. 

o  Depression is a significant psychiatric problem and rates of suicide are higher in HD patients than the general population.  Case reports support using tricyclic as well as newer antidepressants.

o  Agitation is also common, and a small number of patients develop psychosis.  Atypical neuroleptics are commonly used.  Emotional lability (including episodes of extreme anger) can respond to propranolol.

o  Low doses of scheduled benzodiazepines before meals or propranolol are used to control motor manifestations and anxiety related to eating.  

o  Establishing strict daily and hourly routines can help lessen anxiety, short-term memory deficits, intrusive thoughts, and fear of abandonment.

·   Cognitive Deficits: gradual loss of memory and executive function are common.  Consequently, increasing impairments in initiating movements and conversation occur.  Yes/no questions may be preferable over open-ended questions when cognitive impairments become severe.   

 

Advance Care Planning   Advanced care planning should be performed as early as possible, prior to cognitive impairment.  Of particular importance is establishing a health care power of attorney, as well as documenting guidance to families for likely decisions they will face (such as tube feeding and mechanical ventilation).  Some states require clear evidence that a patient would want tube feeding withheld or withdrawn at the end of life and patients should be instructed to document this if consistent with their wishes.  See also Fast Facts #12, 65, 162, and 178 for further discussion of advance care planning.

 

Terminal Care   Hospice services should be considered for all patients with advanced disease.  There are no evidence-based criteria for determining a 6 month prognosis; web-based reference 13 however provides some guidance.  Labored breathing, secretion management, and restlessness are common terminal symptoms – see Fast Facts #1, 60, 109, 158, and 176.

 

References

 

1. Moskowitz CB, Marder K.  Palliative care for people with late-stage Huntington’s disease.  Neurologic Clinics. 2001; 9(4):849-865.
2. Bonelli RM, Wenning GK. Pharmacological management of Huntington’s disease: an evidence-based review.  Curr Pharm Design. 2006; 12(21):2701-20.
3. Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006; 66(3):366-72.
4. Paulsen JS, Hoth KF, Nehl C, Stierman L.  Critical periods of suicide risk in Huntington’s disease. Am J Psychiatry. 2005 ; 162(4):725-31.
5. Folstein SE.  Huntington’s disease: a disorder of families. The Johns Hopkins University Press, Baltimore, MD. 1989.
6. Nance MA, Sanders G.  Characteristics of individuals with Huntington’s disease in long-term care. Movement Disorders. 1996; 11:542-548.
7. Sorensen SA, Fenger K. Causes of death in patients with Huntington’s disease and in unaffected first degree relatives.  J Med Genet. 1992; 29:911-914.
8. Lanska DJ, Lavine L, Lanska MJ, Schoenberg, BS.  Huntington’s disease mortality in the United States.  Neurology. 1988; 38:769.
9. Myers RH, Sax DS, Koroshetz WJ, et al. Factors associated with slow disease progression in Huntington’s disease.  Arch Neurol. 1991; 448:800-804.
10. Mitchell S, Buchanan J, Littlehale S, Hamel M.  Tube-feeding versus hand-feeding nursing home residents with advanced dementia: a cost comparison.  J Am Med Direct Assn. 2003; 4(1):27-33.
11. Vamos M, Hambridge J, Edwards M, Conaghan J. The impact of Huntington’s disease on family life.  Psychosomatics. 2007; 48(5):400-404.
12. Wong MT, Chang PC, Yu YL, et al.  Psychosocial impact of Huntington’s disease on Hong Kong Chinese families.  Acta Psychiatry Scand. 1994; 90:16-18.
13. Hospice Eligibility Flipchart: Huntington’s Disease.  VistaCare Inc. Available at:  http://www.vistacare.com/eligibility/flipchart.  Accessed December 7, 2007.
14. Foroud T, Gray J, Ivashina J, Conneally PM. Differences in duration of Huntington’s disease based on age at onset.  J Neurol Neurosurg Psych. 1999; 66:52-56.

This Fast Fact is also available at EPERC.  

#200: Non-opioid anti-tussives

FAST FACT AND CONCEPT #200

NON-OPIOID ANTI-TUSSIVES

Sean Marks MD and Drew A Rosielle MD

 

Background   Cough is a common, and at times distressing, symptom.  Fast Fact #199 discussed the use of centrally-acting drugs – opioids – for the symptomatic treatment of cough.  This Fast Fact will address peripherally-acting agents.

 

Controversies   Commonly used prescription and over-the-counter anti-tussive formulations which contain some combination of antihistamines (e.g. diphenhydramine), a mucolytic (e.g. guaifenesin), and/or dextromethorphan are often used for acute cough due to upper respiratory infections and acute bronchitis.  Evidence for these agents in the acute setting is poor (either no better than placebo or sweet syrup) and cannot be recommended.  Due to concerns about inadvertent overdose and lack of efficacy, these products are now being actively discouraged for use in the pediatric setting.

 

Peripherally-acting Anti-tussives

·   Sweet syrups are commonly used as cough suppressants, whether as bases for prescription elixirs (such as codeine with guaifenesin) or home remedies (honey, simple syrup).  The mechanism of action is unknown; some authors hypothesize it acts as a protective barrier to sensory receptors in the throat that heighten the cough reflex.  A few controlled trials have shown sweet syrups reduce coughing in upper respiratory infections.

·   Benzonatate inhibits cough by anesthetizing stretch receptors in the respiratory tract.  Its duration of action is 3-8 hours; dosed at 100-200 mg three times a day. No published controlled studies confirm its effectiveness but multiple uncontrolled studies support its use.  Side effects are uncommon but include sedation, headache, bronchospasm, and nausea.  Expert opinion recommends adding it to an opioid.

·   Antihistamines and anticholinergics are often part of combination anti-tussive elixirs with or without an opioid.  Anticholinergics such as hyoscyamine and scopolamine are most helpful in the setting of copious upper respiratory secretions leading to cough.  See Fast Fact #109 for dosing information.

·   Expectorants thin bronchial secretions and ease expectoration.  Examples include guaifenesin (200-400 mg every 4 hours) and nebulized acetylcysteine or hypertonic saline.  Empirically they have been recommended for severe, chronic, wet coughs.  Because they may increase fluid in the respiratory tract, they are not recommended if the cough reflex is diminished.

·   Nebulized local anesthetics are thought to work by anesthetizing afferent receptors in the respiratory tract.  There have been no trials evaluating their effectiveness; anecdotally they have been reported to be effective for refractory cough.  Published regimens include lidocaine 2% solution, 5 mL nebulized every 6 hours; and bupivacaine 0.25%, 5 mL nebulized every 8 hours.  Bronchospasm is a potential side effect.

·   Other agents such as bronchodilators and corticosteroids have not been shown to be effective apart from specific indications (e.g. for COPD or asthma exacerbations).  Paroxetine, amitriptyline, gabapentin, and benzodiazepines have all been anecdotally reported to have efficacy in chronic, refractory cough. 

 

Recommendations   Treatment for cough should be directed at the underlying cause if feasible and consistent with a patient’s prognosis and goals of care.  When symptomatic treatment for a distressing cough is necessary, it is reasonable to start with an opioid product, adding benzonatate if needed.  A trial of anticholinergics and expectorants for the indications described above is reasonable, but they should be stopped after a couple days if they have no effect.  Sweet syrups appear to be helpful in upper respiratory infections; their role otherwise is uncertain.  If these strategies fail to control distressing symptoms, other less studied approaches such as inhaled lidocaine are appropriate.

 

References

1. Homsi J, Walsh D, Nelson KA.  Important drugs for cough in advanced cancer.  Support Care Cancer. 2001; 9: 565-74.
2. Estfan B, LeGrand S.  Management of cough in advanced cancer. J Support Oncol. 2004; 2: 523-7.
3. Von Gunten CF. Interventions to manage symptoms at the end of life.  J of Pall Med. 2005; 8(1): 88-94.
4. Adam J.  Pan-Glasgow palliative care algorithm 2005 – Palliation of cough.  Palliative Care Formulary 2^nd Edition. Radcliffe Medical Press Ltd. 2002.
5. Davis CL.  ABC of palliative care: breathlessness, cough and other respiratory problems. BMJ. 1997; 315: 931-4.
6. Sutton PP, Gemmell HG, Innes N, Davison J, Smith FW, Legge JS, Friend JA.  Use of nebulised saline and nebulised terbutaline as an adjunct to chest physiotherapy. Thorax. 1988; 43(1): 57-60.
7. Irwin RS.  Complications of cough.  Chest. 2006; 129: 54S-58S.
8. Homsi J, et al.  Symptom evaluation in palliative medicine: patient report vs systematic assessment.  Support Care Cancer.  2006;14:444-453.
9. Lingerfelt BM, et al.  Nebulized lidocaine for intractable cough near the end of life.  J Support Oncol.  2007; 7:301-2.
10. Chung KF.  Currently available cough suppressants for chronic cough.  Lung. 2008 [E-pub ahead of print, available Oct 2, 2007].  DOI: 10.1007/s00408-007-9030-1.
11. Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM.  Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents.  Arch Pediatr Adolesc Med. 2007;161:1140-1146.
12. Schroeder K, Fahey T.  Systematic review of randomized controlled trials of over the counter cough medicines for acute cough in adults.  BMJ. 2002;324:1-6.
13. Fuller RW, Jackson DM.  Physiology and treatment of cough.  Thorax. 1990;45:425-30.
14. Smith SM, SchroederK, Fahey T. Over-the-countermedications for acute cough in children and adults in ambulatory settings. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD001831. DOI: 10.1002/14651858.CD001831.pub3.

This Fast Fact is also available at EPERC.  

#199: Opioids for cough

FAST FACT AND CONCEPT #199

OPIOIDS FOR COUGH

Sean Marks MD and Drew A Rosielle MD

Background   Cough is a common, and at times distressing, symptom.  Up to 40% of advanced cancer patients report cough, and while a smaller percentage find their cough distressing, severe cough can lead to dyspnea, nausea/vomiting, sleep impairment, chest and throat pain, and impaired communication.  This Fast Fact will focus on the use of opioids for the symptomatic treatment of cough.  Fast Fact #200 will address other agents for cough. 

 

Etiologies & Evaluation   Common etiologies of cough include infections of the upper and lower airway, asthma and COPD, lung cancer or lung metastases, interstitial pulmonary processes (such as lymphangitic tumor spread or pulmonary edema), gastroesophageal reflux, aspiration, and drugs.  Common drug causes include ACE inhibitors, NSAIDs, and inhalant medications. Evaluating for reversible causes is appropriate if consistent with the goals of care and prognosis.  If feasible, treatment should be directed at the underlying cause.  Many patients however will benefit from symptomatic therapy for a distressing cough while waiting for acute therapy to work or have a chronic cough not amenable to treatment (e.g. cough due to advanced lung cancer).  

 

Opioids are the only clearly effective centrally-acting anti-tussive drugs and are thought to work by suppressing the brainstem cough center through mu and kappa opioid receptor agonism.  They are the first-line symptomatic treatment for severe, distressing cough.  All opioids used to treat cough have typical opioid side effects such as sedation, constipation, and nausea.  

 

·   Codeine: Duration of action is 4 hours; usual adult dose is 10-20 mg every 4-6 hours.  It has shown to be effective for acute and chronic cough in several placebo-controlled trials.  It is available alone or as an elixir with guaifenesin.

 

·   Dextromethorphan:  Duration of action 3-6 hours; usual adult dose is 10-20 mg every 4-6 hours.  It is the most commonly used anti-tussive.  Confirmed to be as effective as codeine for cough in multiple studies.  It is available alone or as an elixir with guaifenesin.  Note: dextromethorphan inhibits the cytochrome P450 system and thereby affects the metabolism of many drugs.  Dextromethorphan can also cause a serotonin syndrome if used with serotonergic drugs such as antidepressants.    

 

·   Hydrocodone: Duration of action 4-6 hours; usual dose 5-10 mg every 4 hours.  Hydrocodone is only available as a combination product in the US: as a short-acting elixir with the anticholinergic drug homatropine or as an extended release elixir with the antihistamine chlorpheniramine (dosed at 10 mg every 12 hours).  These other agents magnify hydrocodone’s sedative effects, and limit the maximum dose a patient can take.  Hydrocodone has been shown to be as effective as codeine in head to head studies but with fewer gastrointestinal side-effects.  For this reason it is considered by many experts as the anti-tussive of choice (Homsi 2001).

 

·   All opioid analgesics have anti-tussive activity and their use has been mostly based on convention; there is no strong evidence that any one opioid has superior efficacy for cough.  For patients already taking opioids for pain, it is unclear whether adding a second opioid such as codeine for cough is effective.  One uncontrolled, open-label study showed hydrocodone to be helpful in this setting; it has not been repeated (Homsi 2001). 

 

Fast Fact #200 will discuss non-opioid agents for cough, as well as address some general treatment strategies.

 

References

1. Homsi J, Walsh D, Nelson KA.  Important drugs for cough in advanced cancer.  Support Care Cancer. 2001; 9: 565-74.
2. Estfan B, LeGrand S.  Management of cough in advanced cancer. J Support Oncol. 2004; 2: 523-7.
3. Von Gunten CF. Interventions to manage symptoms at the end of life.  J of Pall Med. 2005; 8(1): 88-94.
4. Adam J.  Pan-Glasgow palliative care algorithm 2005 – Palliation of cough.  Palliative Care Formulary 2^nd Edition. Radcliffe Medical Press Ltd. 2002.
5. Davis CL.  ABC of palliative care: breathlessness, cough and other respiratory problems. BMJ. 1997; 315: 931-4.
6. Homsi J, Walsh D, Nelson KA, Sarhill N, Rybicki L, LeGrand SB, Davis M.  A phase II study of hydrocodone for cough in advanced cancer.  Am J Hospice Palliat Care. 2002;19: 49-56.
7. Turturro MA, Paris PM, Yealy DM, Menegazzi JJ.  Hydrocodone versus codeine in acute musculoskeletal pain.  Ann Emerg Med. 1991; 20: 1100-03.
8. Irwin RS.  Complications of cough.  Chest. 2006; 129: 54S-58S.
9. Homsi J, et al.  Symptom evaluation in palliative medicine: patient report vs systematic assessment.  Support Care Cancer.  2006;14:444-453.

This Fast Fact is also available at EPERC.  

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