Monday, October 27, 2008

#209: Malignant Pericardial Effusions

MALIGNANT PERICARDIAL EFFUSIONS

Vincent Thai MD

Introduction   Malignant pericardial effusions (MPEs) are a rare complication of advanced cancer, but are associated with high morbidity and mortality.  This Fast Fact discusses the diagnosis and management of MPEs.

Epidemiology and Prognosis   Approximately 10% of patients with cancer develop cardiac metastases, with ~75% of these affecting the epicardium (1, 2).  Only a third of these, however, will develop clinically significant MPEs (1).  Lung and breast cancers are the most common causes.  MPEs are associated with a poor prognosis.  Studies suggest a median survival of 2-3 months after a MPE is diagnosed, with a mean survival of 5 months for solid tumors and 20 months for hematologic malignancies (3, 4).

  

Physiology and Symptoms  The pericardial space is normally filled with less than 50 ml of serous fluid. As this volume increases due to epicardial or pericardial metastases or lymphatic obstruction, both right and left ventricular failure can occur due to inadequate filling.  Signs and symptoms include peripheral and pulmonary edema, chest discomfort, cough, shortness of breath, and orthopnea.  Severity of symptoms depends on the volume of the MPE as well as the rapidity of its accumulation; severe cases can present with cardiac tamponade and shock.  An echocardiogram is indicated whenever a MPE is suspected.  Not only does it confirm the presence of an effusion, but its findings can dictate whether or not urgent treatment is indicated (e.g. if signs of tamponade are evident).  A diagnostic pericardiocentesis or pericardial biopsy is sometimes needed to confirm the cause of the effusion.

 

Treatment Options    

·   Systemic chemotherapy or radiotherapy are effective for chemo- or radio-sensitive tumors such as previously untreated breast cancer and many lymphomas. Reaccumulation rates for both modalities are about 1/3 overall, depending on the patient’s overall course and response to therapy (5).

·   Pericardiocentesis results in immediate symptom relief in most patients, however the effusion may rapidly re-accumulate in many patients, needing repeat pericardiocentesis (within 1-2 weeks in some series) (6). 

·   Pericardial sclerosis involves instilling a sclerosing agent with the intention of scarring the pericardium to the epicardium, preventing reaccumulation of the MPE (similar to pleural effusions – see Fast Fact #157).  Multiple agents have been studied including doxyclycline, minocycline, and bleomycin.  Success rates (no reaccumulation at 30 days) are about 70-90% (7, 8).  Longer term success rates have not been defined due to the poor survival of study patients. The major side effect is chest pain (50-70%), cardiac arrhythmias, and fever (8, 9, 10).  In head to head comparisons with doxycycline, bleomycin has been shown to have fewer side effects and to lead to shorter hospitalizations (10, 11, 12).

·   Surgical decompression therapies range from less invasive (balloon pericardiotomy, subxiphoid or thorascopic pericardiostomy) to more extensive (open thoracotomy with pericardial stripping).  A pericardial ‘window’ (which allows ongoing drainage of fluid externally or internally such as into the pleural cavity) is often created.  Case series have suggested reaccumulation rates with surgical therapies are low (less than 15% up to 10 months out) (13, 14, 15).

 

Decision-Making   The treatment of MPEs depends on how urgently treatment is needed, the likelihood of the tumor responding to anti-neoplastic treatments, and the anticipated survival of the patient.  A multidisciplinary approach to decision-making, involving input from medical and radiation oncology, cardiology, and thoracic surgery is recommended. Simple pericardiocentesis may be appropriate for patients with short prognoses (less than 1 month), particularly if their MPE is not expected to re-accumulate in their remaining life-span.  A symptomatic patient with no signs of tamponade and a chemotherapy-sensitive tumor such as untreated breast cancer may receive a durable response from a pericardiocentesis for symptom relief, followed by chemotherapy.  Patients with longer prognoses (>1 month) who are expected to re-accumulate their MPEs will likely benefit most from sclerosis or surgical decompression; there is no clear evidence currently suggesting one strategy is superior to the other.  Symptom directed care without specific intervention for the MPE is an appropriate option for patients with very short prognoses and for those who decline more invasive treatments.

 

References

  1. Klatt EC, Heitz DR. Cardiac metastases. Cancer. 1990; 65(6):1456-59.
  2. Abraham KP, Reddy V, Gattuso P. Neoplasms metastatic to the heart: review of 3314 consecutive autopsies. Am.J.Cardiovasc.Pathol. 1990; 3:195-198..
  3. Moores, D.W, Allen K.B, Faber L.P, Dziuban S.W, Gillman D.J, Warren W.H., Ilves R, Lininger L, Subxiphoid pericardial drainage for pericardial tamponade, The Journal of Thoracic and Cardiovascular Surgery 1995, 109 (3), 546-552
  4. Dosios T, Theaskos,N, Angouras D, et al. Risk factors affecting the survival of patients with pericardial effusion submitted to subxiphoid pericardiostomy. Chest. 2003; 124:242
  5. Lamont E, Hoffman PC. Oncologic Emergencies (chapter). In: Principles of Critical Care. 3rd Edition. McGraw Hill; New York: 2005. 
  6. Laham RJ, Cohen DJ, Kuntz RE et al. Pericardial effusion in patients with cancer: outcome with contemporary management strategies. HEART. 1996; 75(1):67-71.
  7. Lashevsky I, Ben Yosef R, Rinkevich D, Reisner S, Markiewicz W. Intrapericardial minocycline sclerosis for malignant pericardial effusion. Chest. 1996;109(6):1452-54.
  8. Maher EA, Shepherd FA, Todd TJR. Pericardial sclerosis as the primary management of malignant pericardial effusion and cardiac tamponade. J Thoracic Cardiovascular Surg. 1996; 112(3):637-643.
  9. Ben Yosef,R.; Phefer,R.; Ge,A.; Catane,R. Management of malignant pericardial effusion Harefuah, 1988, 115, 5-6, 138-141, ISRAEL
  10. Liu G, Crump M, Goss PE, Dancey J, Shepherd FA. Prospective comparison of the sclerosing agents doxycycline and bleomycin for the primary management of malignant pericardial effusion and cardiac tamponade. J Clin.Oncol. 1996; 14(12):3141-47.
  11. Yano T, Yokoyama H, Inoue T, et al. A simple technique to manage malignant pericardial effusion with a local instillation of bleomycin in non-small cell carcinoma of the lung. Oncology. 1994;51:507-509.
  12. van Belle SJ, Volckaert A, Taeymans Y, Spapen H, Block P. Treatment of malignant pericardial tamponade with sclerosis induced by instillation of bleomycin. Int.J.Cardiol. 1987; 16(2):155-160.
  13. Galli M, Politi A, Pedretti F, Castiglioni B, Zerboni S. Percutaneous balloon pericardiotomy for malignant pericardial tamponade. Chest. 1995; 108(6):1499-1501.
  14. Palacios IF, Tuzcu EM, Ziskind AA, Younger J, Block PC. Percutaneous balloon pericardial window for patients with malignant pericardial effusion and tamponade. Cathet.Cardiovasc.Diagn. 199; 22(4):244-49.
  15. Ziskind AA, Pearce AC, Lemmon CC, et al. Percutaneous balloon pericardiotomy for the treatment of cardiac tamponade and large pericardial effusions: description of technique and report of the first 50 cases. J.Am.Coll.Cardiol. 1993; 21(1):1-5.

The original version of this Fast Fact is on the EPERC website.  

Friday, October 10, 2008

#208: Clinical care following withdrawal of dialysis

FAST FACTS AND CONCEPTS #208

CLINICAL CARE FOLLOWING WITHDRAWAL OF DIALYSIS

Sara N Davison MD and Drew A Rosielle MD

 

Background   Fast Fact #207 discussed decision-making around dialysis discontinuation; this Fast Fact addresses care of the patient around the time of discontinuation.

 

Communication and care-planning at the time of dialysis cessation

·         Counsel about what to expect: mean survival following dialysis withdrawal is 8-10 days (although rarely can be many weeks).  Address the likelihood of progressive encephalopathy.

·         Counsel about symptoms (see below).  Reassure patients/families that these can be adequately treated, although drugs with sedating side effects may be necessary to ensure comfort.

·         Recommend continuing fluid restriction (< style="mso-spacerun:yes">  Discuss diet: a liberal, pleasure-based diet is appropriate for many patients although they should be cautioned it could worsen symptoms from edema.

·         Address potential care sites for the final days of life.

·         Review other medical treatments the patient is receiving and discontinue those that will not improve their quality of life while dying; clarify treatment limitations including resuscitation (code) status.

·         Provide emotional/psychological, spiritual, social work, and bereavement support services.

 

Symptom Management   In one cohort of hospitalized patients who stopped dialysis confusion/agitation was reported to affect 70% of patients, followed by pain (55%), dyspnea (48%), nausea (36%), twitching/seizures (27%), anxiety/psychological distress (27%), pruritis (24%), and peripheral edema (21%).  Because of a paucity of clinical research, the following recommendations are largely based on clinical experience and pharmacologic common sense. Many drugs which were previously cleared by dialysis may need to be dose-adjusted or discontinued.  Treatment plans should be frequently re-evaluated, with particular attention to the use of scheduled medications. 

·         Pain management:  Acetaminophen is the agent of choice for mild pain.  Fast Fact #161 addresses opioid use in renal failure.  Fentanyl and methadone are considered safest after dialysis discontinuation, although methadone should only be initiated by clinicians familiar with its use.  Toxic hydromorphone metabolites, previously cleared by dialysis, can accumulate rapidly once dialysis is stopped and it should be used with caution and close monitoring of side effects.  Gabapentin and pregabalin quickly accumulate once dialysis is stopped and should be discontinued or severely dose-reduced (see Fast Fact #49).

·         Shortness of breath:  Oxygen, positioning, and opioids are the mainstays of therapy (see Fast Fact #27). Ultrafiltration is not recommended as it can be distressing for patients/family to see the patient back on a therapy which appears similar to hemodialysis. For the occasional patient who has a residual urine output of >100ml/day, high dose diuretics can be used.   

·         Anxiety/agitation/restlessness:  Assure pain and psychosocial issues are addressed.  Haloperidol or benzodiazepines are effective.  Haloperidol may lower the seizure threshold and the metabolites are excreted in the urine and feces so it is recommended to dose at half the typical starting dose following dialysis withdrawal. While benzodiazepines do not accumulate in chronic kidney disease, clinical experience supports starting with very low doses in this population. 

·         Restless legs:  Clonazepam is particularly useful for the restless legs associated with uremia (0.5 – 2.0 mg bid). Clonidine (0.1-0.2 mg bid) can also be used.

·         Muscle cramps: Dialysis patients are often treated with quinine sulphate which accumulates rapidly once dialysis is stopped and should be discontinued.  Clonazepam and other benzodiazepines are better in this setting.

·         Nausea:  Reduced doses of metoclopromide (starting at 5mg bid) are effective for gastroparesis.  Uremia-induced nausea often responds well to dopamine antagonists such as haloperidol and prochloperazine which are often sedating in the context of uremia.  Ondansetron has some advantages as it is less sedating and does not accumulate in kidney failure. 

·         Pruritus: Emollients such as hydrourea cream, ondansetron, and antihistamines may be beneficial.  Gabapentin, while effective, is too toxic in this population to initiate its use.

 

References

1.       Germain MJ, Cohen LM, Davison SN. Withholding and Withdrawing from Dialysis: What We Know About How Our Patients Die.  Seminars in Dialysis. 2007; 20:200-204.

2.       Murtagh FEM, Addington-Hall JM, Donohoe P, Higginson IJ.  Symptom Management in Patients With Established Renal Failure Managed Without Dialysis.  EDTNA ERCA J. 2006; 32:93-98.

3.       Chambers EJ, Germain M, Brown E (Eds.).  Supportive Care for the Renal Patient (1st Edition). Oxford: Oxford University Press; 2004. 

4.       Cohen LM, Germain MJ, Poppel DM.  Practical considerations in dialysis withdrawal.  “To have that option is a blessing.”  JAMA. 2003; 289:2113-2119.

5.       Murtagh FE, Chai MO, Donohoe P, Edmonds PM, Higginson IJ.  The use of opioid analgesia in end-stage renal disease patients managed without dialysis: recommendations for practice.  J Pain Palliat Care Pharmacother. 2007; 21:5-16.

6.       Lugon JR.  Uremic pruritus: a review.  Hemodialysis Intl. 2005; 9:180-88.

 

Author Affiliations:  University of Alberta, Edmonton, Alberta (SND), and the Medical College of Wisconsin, Milwaukee, Wisconsin (DAR).


This Fast Fact is also available at EPERC.