Journal Club Podcast #21: March 2015
A few of the residents join me to discuss the benefits of albumin administration for patients with SBP or those undergoing large volume paracentesis...
Click Tab to ExpandArticles:
Article 1: Bernardi M, Caraceni P, Navickis RJ, Wilkes MM. Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials. Hepatology. 2012 Apr;55(4):1172-81. Answer Key.
Article 2: Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 1999 Aug 5;341(6):403-9. Answer Key.
Article 3: Salerno F, Navickis RJ, Wilkes MM. Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: a meta-analysis of randomized trials. Clin Gastroenterol Hepatol. 2013 Feb;11(2):123-30. Answer Key.
Article 4: Kwok CS, Krupa L, Mahtani A, et al. Albumin reduces paracentesis-induced circulatory dysfunction and reduces death and renal impairment among patients with cirrhosis and infection: a systematic review and meta-analysis. Biomed Res Int. 2013;2013:295153. Answer Key.Vignette:
You are caring for a fifty-year old gentleman with a history of non-alcoholic steatohepatitis with cirrhosis who presents to the emergency department (ED) with increased abdominal distension, shortness of breath, and fevers. His abdomen is distended and tense with mild diffuse tenderness. His temp is 38.7 C, BP is 103/60, HR is 89, and SpO2 is 99% on room air. You check his labs and find a WBC of 13.4, baseline anemia, a creatinine of 1.2, and an INR of 1.4. His chest x-ray reveals small lung volumes without infiltrates or pulmonary edema. A bedside ultrasound reveals a large amount of ascites. You decide to perform both a therapeutic paracentesis to relieve pressure on his diaphragm and improve his respiratory complaints, and send fluid to the lab for cell count, differential, gram stain, and culture given your concern for spontaneous bacterial peritonitis (SBP).
You manage to drain just over 8 liters of fluid, for which the patient is quite thankful. The fluid gram stain reveals abundant polymorphonuclear cells (PMNs) with no organism seen. The cell count reveals 15,000 nucleated cells, of which 89% are PMNs. You feel confident that the patient has SBP and order a dose of cefotaxime. You are admitting the patient to the medicine service when the resident suggests that you administer albumin. She tells you that the American Association for the Study of Liver Diseases (AASLD) recommends albumin administration both following large-volume paracentesis and in the management of select patients with SBP. You follow the resident’s recommendations, but are curious what the evidence actually shows. After your shift you decide to begin your literature search.PICO Question:
Population: Adult patients with cirrhosis and tense ascites undergoing large volume paracentesis
Intervention: Intravenous albumin
Outcome: Death, renal impairment, circulatory dysfunction, hyponatremia
Population: Adult patients with cirrhosis and spontaneous bacterial peritonitis
Intervention: Intravenous albumin + antibiotics
Comparison: Antibiotics alone
Outcome: Death, renal impairment, circulatory dysfunction, hyponatremiaSearch Strategy:
Two MEDLINE searches were conducted via PubMed. A search was performed using the terms albumin AND "spontaneous bacterial peritonitis" which resulted in 230 citations (http://tinyurl.com/l2zy2se). Of these, one systematic review and one large randomized controlled trial were chosen. An additional search was conducted using the terms albumin and paracentesis (http://tinyurl.com/kfau542). This resulted in 414 citations, from which two systematic reviews were chosen.Bottom Line:
Ascites is one of the many complications associated with hepatic cirrhosis, and is associated with a poor prognosis (D’Amico 2006). Ascitic fluid can accumulate to the extent that it impairs functional status, and current guidelines recommend a large volume paracentesis for patients with tense ascites. When such large volumes of ascitic fluid are removed, fluid shifts and a decreased systemic vascular resistance can potentially lead to circulatory dysfunction, hyponatremia, and renal impairment (Lindsay 2014). The administration of intravenous albumin can theoretically reduce the risk of these complications, though this practice remains controversial (Manzocchi 2012, Caraceni 2013).
Two systematic reviews and meta-analyses published on the use of albumin following large volume paracentesis found similar results (Bernardi 2012, Kwok 2013). The use of albumin was shown to significantly reduce the risk of circulatory dysfunction, with a number needed to treat (NNT) of 2, and the risk of hyponatremia, with a NNT of 8. For these outcomes, albumin was shown to outperform other volume expanders as well. Albumin was not, however, shown to reduce mortality, renal impairment, ascites recurrence, or hospital readmission. While this evidence suggest some benefit to albumin administration, the two outcomes for which albumin demonstrated an improvement are of unclear clinical relevance. As a result, it is difficult make a strong recommendation either for or against albumin administration in patients undergoing large volume paracentesis. The current recommendation from the American Association for the Study of Liver Disease (AASLD) is to consider the administration of albumin (6-8 g/L of fluid removed) for patients undergoing removal of greater than 5 liters. This recommendation is appropriately given a low grade (IIa/C).
With regards to albumin administration in patients with SBP, the evidence is more compelling. A meta-analysis of 4 randomized controlled trials comprising 288 patients found significant reductions in both the risk of renal impairment (OR 0.21, 95% CI 0.11-0.42) and mortality (OR 0.34, 95% CI 0.19-0.60) with NNTs of 4 and 5, respectively. The included studies were, admittedly, of only moderate quality, with only one of them being blinded. The largest of these trials (Sort 1999), which included nearly half of the patients in the meta-analysis, independently demonstrated significant reductions in renal impairment (OR 0.21) and both in-hospital and 90-day mortality (ORs of 0.26 and 0.41, respectively). This study was not blinded, and more importantly was limited by a difference in baseline bilirubin levels between the two group: the mean bilirubin in the control group was 6 ± 1 compared to 4 ± 1 in the group that received albumin. This difference is important, as the study demonstrated on multivariate logistic regression that elevated bilirubin levels were independently predictive of a higher risk of both renal impairment and death.
Despite this limitation, the AASLD recommendation is to administer albumin (1.5 g/kg within 6 hours of diagnosis of SBP followed by 1.0 g/kg on day 3) in patients with a serum creatinine > 1 mg/dL OR BUN > 30 mg/dL OR bilirubin > 4 mg/dL. It should be noted that the limited administration based on these laboratory abnormalities is based on a single observational cohort study, and seems somewhat arbitrary.
Both therapeutic and diagnostic paracentesis are common procedures in emergency medicine, and the diagnosis and initial management of SBP fall well within our practice parameters. Given the increased boarding times observed in many EDs, it is prudent that the emergency physician be aware of treatment modalities that require initiation within the first several hours of patient care. As a result, it seems reasonable to begin the administration of albumin to patients with SBP concomitantly with antibiotics while the patient is still in the ED, as this has been shown to decrease the risk of both renal impairment and mortality. It is also reasonable to consider albumin infusion in patients undergoing large volume paracentesis (more than 5 liters of ascitic fluid removed), though the evidence in support of this is much less compelling.
54 yo F with no PMHx, but admittedly has not been seen by an MD in many years, presents after her daughter visited from our-of-town and found her slightly confused. The patient is disoriented, but able to provide some history. She describes progressive fatigue over several weeks. Vitals signs are remarkable for hypothermia 94F, HR 52, BP 150/90, RR 12, SpO2 100%RA. Exam is notable for AAO2, no focal neuro deficits, prominent facial swelling, and non-pitting lower extremity edema. FS glucose 160. Laboratory analysis is concerning for mild hyponatremia and severe hypothyroidism.
This patient is suffering from myxedema coma. Contrary to its name, myxedema coma does not require your patient be in a comatose state. It refers to AMS in the setting of severe hypothyroidism. Additionally, patients may also be hypothermic, bradycardic, hypotensive, hypoglycemic, and hyponatremic. It is important to rule out more common causes of AMS, while keeping hypothyroid high on the differential in this patient. Checking a fingerstick, as always, should be done at arrival in patient’s with new AMS.
This patient should be admitted and receive IV thyroid replacement. Oral medications may not be fully absorbed secondary to gastrointestinal edema. Finally, myxedema (a dermatologic condition) does not necessarily need to be present in myxedema coma.
Credit: This article is largely based on http://www.nejm.org/doi/full/10.1056/NEJMicm1403210
A guest blog from Larshan Perinpam (President of ISAEM) and Anh-Nhi Thi Huynh (Vice president of external affairs, ISAEM)
ISAEM is an organization established to take Emergency Medicine student Interest groups (EMIGs) extracurricular activities to a whole new level, not only locally or nationally but also worldwide.
ISAEM is the abbreviation of the International Student Association of Emergency Medicine. It is the first international Student organization of it’s kind within Emergency Medicine (EM) and was founded in Denmark in October 2013. ISAEM’s primary aim is to create International relations between EMIGs all over the world.
In the United States, EM was founded more than 40 years ago, and today it is a well-established specialty that occupies the Emergency Department (ED), which in most cases is the front door into the hospital. By having an individual specialty within EM you are able to provide a better and more optimized patient care. In many countries (Norway, Denmark, Brazil, etc.) EM does not exist as an individual specialty. In such countries EDs are occupied by the already established individual specialties (cardiology, general surgery, infectious diseases, primary physicians, orthopedic surgeons etc.) and many EDs does not have its own physician staff.
In order to develop a department the first step is to have its own staff, a staff that is continuous and present in the department on a daily basis. These are just some of the few challenges that are being faced in the EDs worldwide. Some countries already have an established specialty within EM, but it is still under development. Furthermore these countries are also facing recruitment problems due to the rough working conditions.
The members of ISAEM are local and national EMIGs around the world. ISAEM believes that the best possible way to recruit future staff into EM is through the EMIGs that are already established in many medical schools. We need to optimize the extra curricular activities in comparison to all other medical student interest groups, who have their interest within another established specialty.
In ISAEM we believe that by connecting every EMIG on a international level we will be able to; exchange ideas, find inspiration in activities created by different EMIGS, be able to further develop the local EMIGs and create a foundation for the next generation of physicians who wishes to pursue a careare in EM
Since the establishment of ISAEM we have strived to promote ISAEM in the best way possible by attending international EM meetings (ACEP, EuSEM14, ESEM2014 etc.); finding the right collaboration partners (EMRA, DASEM, EuSEM, ESEM etc.) and focused on creating a stable and strong infrastructure of the organization. Recently ISAEM launched its latest initiative to further develop EM among medical students by creating the ISAEM National Ambassador program. The National Ambassadors will play the part as bridge-builders between the local EMIGS and ISAEM.
The practice of EM is extremely diverse and various internationally and ISAEM wishes to create opportunities in order to expand the experience and understanding for students with an interest in EM. Therefore ISAEM decided to develop an international ED Observership program in order to give medical students the opportunity to see how EM is practiced in different cultures and settings. This will also help to inspire the individual student to further develop Emergency Medicine in their home country.
Currently ISAEM is represented by five countries/members (Denmark, Netherland, Brazil, US and the Netherlands.) These already represent more than 2000 EM interested medical students. In the end of April 2015, ISAEM wish to enroll more EMIGs and by the end of 2015, ISAEM aim to represent more than 20.000 EM interested medical students worldwide! We want to create the biggest international student network within EM.
ISAEM is slowly developing and our current achievements is all because of our members, partners and the medical students who dedicate their free time in order to develop ISAEM. This work is what defines ISAEM and the future of ISAEM. In ISAEM we believe “alone we can go fast but together we will go far”.
If you find this interesting, please don’t hesitate to contact us:
We are looking forward to further develop EM among medical students with you.
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