The serum creatinine of my patient originally admitted for management of tense ascites is slowly rising. How concerned should I be?

Although the causes of increasing serum creatinine (SCr) in patients with cirrhosis are legion (eg, sepsis, acute tubular injury, and intravascular volume depletion due to over-diuresis, gastrointestinal bleed, or other causes), the most feared cause is often hepatorenal syndrome (HRS). HRS is a functional renal impairment that reflects the final pathophysiological stages of systemic circulatory impairment1, and significantly contributes to a worsening prognosis in patients with cirrhosis2. For example, without treatment, in patients whose SCr doubles in less than 2 weeks (type I HRS) the median survival is less than 2 weeks , while in those who develop a more gradual renal impairment (type II HRS) the median survival is 6 months3.

Physiologically, HRS is a culmination of significant vasodilation in the splanchnic arteries which, in time, leads to reduced organ perfusion due to a drop in the cardiac output. The associated increase in the activity of the renin-angiotensin-aldosterone and the sympathetic nervous systems contributes to sodium and water retention, and further exacerbates intra-renal vasoconstriction and ascites3.

The primary goal in the medical management of HRS is to increase splanchnic vascular resistance4, often by administering a combination of IV albumin, octreotide and other vasoconstricting agents (eg, midodrine, norepinephrine, or terlipressin [unavailable in US and Canada]).  Of interest, in addition to expanding the circulating plasma volume, albumin may have a vasoconstricting effect by binding to endotoxins, nitric oxide, bilirubin and fatty acids4!

 

References

  1. Arroyo V, Fernandez J, Gines P. Pathogenesis and treatment of hepatorenal syndrome. Semin Liver Dis 2008;28:81-95.
  2. Salerno F, Gerbes A, Ginès P, et al. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep;56(9):1310-8.
  3. Cardenas A, Gines P. A Patient with cirrhosis and increasing creatinine Level: What Is It and what to do? Clin Gatroenterol Hepatol 2009;7:1287–1291. 
  4. Baraldi O, Valentini C, Donati G, et al. Hepatorenal syndrome: Update on diagnosis and treatment. World J Nephrol. 2015;4:511-20.

Contributed by Alireza Sameie, Medical Student, Harvard Medical School

The serum creatinine of my patient originally admitted for management of tense ascites is slowly rising. How concerned should I be?

What is the clinical significance of “white bile” from my patient’s gallbladder drain?

“White bile” (WB) (Figure) is a clear sero-mucous secretion of gallbladder that is largely devoid of bilirubin and bile salts. It arises from glycoproteins that are normally secreted by the mucosal glands of the gallbladder infundibulum and neck, and is thought to shield the gallbladder wall from the lytic action of bile.

WB is observed in “hydrops” of gallbladder and is caused by absorption of bile by the gallbladder wall in the setting of persistent cystic duct obstruction1. It is commonly held that in persistent cystic duct obstruction, bile in the gallbladder is eventually absorbed into the lymphatics and blood vessels but that the gallbladder epithelium continues to produce clear sero-mucous secretions. In this setting, dilatation, perforation, and atrophy of the gallbladder lumen may also occur1-3.  Early cholecystostomy tube placement or cholecystectomy is often indicated1,3.

Common etiologies of persistent cystic duct blockage in adults include, stone impaction, cystic duct stenosis, tumors/polyps, and parasites (eg, ascariasis).

Figure: “White bile” drainage from a cholecystostomy drain of a patient with cholecystitis and persistent cystic duct blockage due to stones. The drainage was completely clear with mucous characteristics. 

whitebile

Reference:

  1. Schwartz, Seymour I, Brunicardi, F. Charles., eds. Schwartz’s Principles Of Surgery. New York : McGraw-Hill Medical, 2011.
  2. Ahmed A, Cheung RC, Keeffe EB. Management of gallstones and their complications. Am Fam Physician 2000; 61, 1673-1680.
  3. Lawrence S. Friedman, Mark Feldman. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease 10th Edition. Philadelphia, PA: Elsevier, 2015.

Contributed by Alireza Sameie, Medical Student, Harvard Medical School

What is the clinical significance of “white bile” from my patient’s gallbladder drain?

My elderly patient is scheduled to undergo elective surgery? Is there an objective “stress test for the brain” that may predict postoperative delirium?

Possibly, in the near future! Although the pathophysiology of postoperative delirium (POD) is not fully understood, a recently proposed conceptual model of delirium may provide a basis for preoperative neurophysiologic testing1.

According to this model, delirium is a “consequence of the breakdown in brain network dynamics” precipitated by insults or stressors (eg, surgery) in persons with low brain resilience ie, low connectivity between brain regions and/or deficient neuroplasticity (the ability of brain to reorganize itself by forming new neural connections).  

As expected,  patients with strong baseline connectivity and optimal neuroplasticity would not be expected to have POD, whereas those with weakened connectivity (eg baseline cognitive dysfunction) and/or suboptimal neuroplasticity (eg due to aging) may be at higher risk. Transcranial magnetic stimulation (TMS)  is considered a powerful tool that measures the connectivity and plasticity of the brain through induced perturbation.  When applied in repetitive trains, TMS produces changes in cortical excitability that can be measured using electromyography and EEG,  and is thought to have the ability to assess neuroplasticity 2. If proven effective in predicting POD, it could revolutionize preoperative risk assessment in the elderly! Stay tuned!

 

Reference

  1. Shafi MM, Santarnecchi E, Fong TG, et al. Advancing the neurophysiological understanding of delirium. J Am Geriatr Soc 2017. DOI:10.1111/jgs.14748.
  2. Pascual-Leone A, Freitas C, Oberman L, et al. Characterizing brain cortical plasticity and network dynamics across the age-span in health and disease with TMS-EEG and TMS-fMRI. Brain Topogr 2011, 24:302-15.
My elderly patient is scheduled to undergo elective surgery? Is there an objective “stress test for the brain” that may predict postoperative delirium?

What complications should I look for in my hospitalized patient suspected of having check-point inhibitor toxicity?

Targeting the host immune system via monoclonal antibodies known as checkpoint inhibitors (CPIs) is an exciting new strategy aimed at interfering with the ability of cancer cells to evade the patient’s existing antitumor immune response. CPIs have been shown to be effective in a wide variety of cancers and are likely to be the next major breakthrough for solid tumors1-3. Unfortunately, serious—at times fatal— immune-related Adverse Events (irAEs) have also been associated with their use4,5.

IrAEs occur in the majority of patients treated with nivolumab (a programmed death 1 [PD-1] CPI] or ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] CPI)1. The severity of irAEs may range from mild (grade 1) to very severe (grade 4). Grading system categories discussed in more detail at link below:

https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf.

Although fatigue, diarrhea, pruritis, rash and nausea are not uncommon, more severe grade (3 or 4) irAEs may also occur (Figure). The most frequent grade 3 or 4 irAEs are diarrhea and colitis; elevated ALT or AST are also reported, particularly when CPIs are used in combination. Hypophysitis, thyroiditis, adrenal insufficiency, pneumonitis, enteritis sparing the colon with small bowel obstruction, and hematologic and neurologic toxicities may also occur.

Generally, skin and GI toxicities appear first, within a few weeks of therapy, followed by hepatitis and endocrinopathies which usually present between weeks 12 and 245. High suspicion and early diagnosis is key to successful management of irAEs.

Figure. Selected irAEs associated with nivolumab and ipilimumab (adapted from reference 1).

chceky2

References

  1. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23-34.
  2. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med. 2015;373:1627-1639.
  3. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med 2015; 373:123-135.
  4. Weber JS, Yang JC, Atkins MB, Disis ML. Toxicities of immunotherapy for the practitioner. J Clin Oncol 2015;33:2092-2099.
  5. Weber JS. Practical management of immune-related adverse events from immune checkpoint protein antibodies for the oncologist. Am Soc Clin Oncol Educ Book. 2012:174-177.

Contributed by Kerry Reynolds, MD, Mass General Hospital, Boston.

 

 

 

 

What complications should I look for in my hospitalized patient suspected of having check-point inhibitor toxicity?

Why does my patient with alcoholic liver disease have spider angiomas?

Spider angiomas (SAs), collections of small blood vessels radiating from a central, dilated arteriole that form near the surface of the skin, are  found in 10-15% of healthy adults and young children, as well as in a variety of conditions, including pregnancy, women taking oral contraceptive pills (OCPs),  thyrotoxicosis, and chronic liver disease1.  Although the exact mechanism of their formation has not been fully elucidated, several hypotheses have been offered.

Some hypothesize that SAs form due to arteriolar vasodilation caused by estrogen excess that occurs as a result of impaired hepatic metabolism in cirrhosis2;this is supported by their association with other high-estrogen states, such as in pregnancy and OCP use. The vasodilatory effects of substance P, a neuropeptide partially inactivated by the liver and elevated in patients with liver disease, may also play a role3.  Neovascularization promoted by vascular endothelial growth factor and basic fibroblast growth factor released by damaged hepatocytes has also been implicated4. Alcohol itself may contribute, as SAs are more commonly seen in individuals with alcoholic cirrhosis than in those with non-alcoholic causes of liver disease2.

For unknown reasons, in adults, spider angiomas most commonly occur in areas drained by the superior vena cava, namely the face, arms, neck, and chest.

References

  1. Khasnis A, Gokula RM. Spider nevus. J Postgrad Med 2002;48:307.           
  2. Li CP, Lee FY, Hwang SJ, et al., Spider angiomas in patients with liver cirrhosis: role of alcoholism and impaired liver function. Scand J Gastroenterol 1999;  34: 520-3.
  3. Li CP, Lee FY, Hwang SJ, et al., Role of substance P in the pathogenesis of spider angiomas in patients with nonalcoholic liver cirrhosis. Am J Gastroenterol 1999; 94: 502-7.
  4. Li CP, Lee FY, Hwang SJ,  et al., Spider angiomas in patients with liver cirrhosis: role of vascular endothelial growth factor and basic fibroblast growth factor. World J Gastroenterol 2003; 9: 2832-5.

Contributed by Camille Mathey-Andrews, Medical Student, Harvard Medical School

 

Why does my patient with alcoholic liver disease have spider angiomas?

Is intermittent urethral catheterization preferred over continuous indwelling catheters for short-term management of urinary retention in my hospitalized patient?

For continuous urethral catheterization (CUC), the estimated daily risk of acquisition of bacteriuria is 3% to 8%1-3.  For intermittent urethral catheterization (IUC), the incidence of bacteriuria is 1% to 3% per insertion4. The Infectious Diseases Society of America recommends that IUC should be considered as an alternative to short-term CUC to reduce catheter-associated bacteriuria or UTI based on “poor evidence”  (Category C) and, as relates to symptomatic UTIs, without properly designed randomized-controlled studies2.  

A Cochrane systematic review of CUC vs IUC in hospitalized patients failed to find any significant differences between the 2 interventions as relates to the rates of symptomatic UTI and asymptomatic bacteriuria in hospitalized patients requiring short-term catheterization5.   Of interest, nearly 3 times as many people developed acute urinary retention with IUC compared to CUC in this study (16% vs 45%, respectively, RR 0.45, 95% CI 0.22-0.91).  

In short, despite its theoretical advantage in reducing the risk of UTIs due to lack of a constant presence of a catheter, solid data to support preference of ICU over CUC in short-term management of urinary retention in hospitalized patients is still lacking.

References

  1. Lo, Nicolle LE, Coffin SE, et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol 2014;35:464-78.
  2. Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2010;50:625-663.
  3. Kunin CM, McCormack RC. Prevention of catheter-induced urinary-tract infections by sterile closed drainage. N Engl J Med 1966;274:1155-61.
  4. Saint S, Lipsky BA. Preventing catheter-related bacteriuria: Should we? Can we? How? Arch Intern Med 1999;159:800-808.
  5. Kidd EA, Stewart F, Kassis NC, et al. Urethral (indwelling or intermittent) or suprapubic routes for short-term catheterization in hospitalized adults (review). Cochrane Database of Systematic Reviews 2015; Issue 12. Art No. :CD004203.

 

 

 

Is intermittent urethral catheterization preferred over continuous indwelling catheters for short-term management of urinary retention in my hospitalized patient?

Is treatment of pneumococcal pneumonia with bacteremia any different than pneumococcal pneumonia without bacteremia?

In the absence of disseminated infection such as meningitis or endocarditis, there is no convincing evidence that bacteremic pneumococcal pneumonia (BPP) requires either longer course of IV or oral antibiotics. In fact, although previously thought to have a worse prognosis, recent data have failed to demonstrate any difference in time to clinical stability, duration of hospital stay or community-associated pneumonia (CAP)-related mortality with BPP when other factors such as patient comorbidities and severity of disease are also considered1,2

Although many patients with CAP receive 7-10 days of antibiotic therapy, shorter durations as little as 5 days may also be effective3,4.  Generally, once patients with BPP have stabilized on parenteral therapy, a switch to an appropriate oral antibiotic (eg, a β-lactam or a respiratory quinolone such as levofloxacin) can be made safely5.  Although large randomized-controlled studies of treatment of BPP are not available, a cumulative clinical trial experience with levofloxacin for patients with BPP reported a successful clinical response in >90% of patients (median duration of therapy 14 d)6. Resistance to levofloxacin and failure of treatment in pneumococcal pneumonia (with or without bacteremia), however, has been rarely reported7.

 

References

  1. Bordon J, Peyrani P, Brock GN. The presence of pneumococcal bacteremia does not influence clinical outcomes in patients with community-acquired pneumonia. Chest 2008;133;618-624.
  2. Cilloniz C, Torres A. Understanding mortality in bacteremic pneumococcal pneumonia. J Bras Pneumol 2012;38:419-421.
  3. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44:S27-72.
  4. Shorr F, Khashab MM, Xiang JX, et al. Levofloxacin 750-mg for 5 days for the treatment of hospitalized Fine Risk Class III/IV community-acquired pneumonia patients. Resp Med 2006;100:2129-36.
  5. Ramirez JA, Bordon J. Early switch from intravenous to oral antibiotics in hospitalized patients with bacteremic community-acquired Streptococcus pneumonia pneumonia. Arch Intern Med 2001;161:848-50.
  6. Kahn JB, Bahal N, Wiesinger BA, et al. Cumulative clinical trial experience with levofloxacin for patients with community-acquired pneumonia-associated pneumococcal bacteremia. Clin Infect Dis 2004;38(supp 1):S34-42.
  7. Davidson R, Cavalcanti R, Brunton JL, et al. Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N Engl J Med 2002;346:747-50.
Is treatment of pneumococcal pneumonia with bacteremia any different than pneumococcal pneumonia without bacteremia?