Question 14

College Answer

• Serum Ammonia
  • Used as an indicator of hepatic encephalopathy
  • Normal values do not rule out encephalopathy – therefore of limited utility in patients with known chronic liver disease
  • Not useful as a monitor during therapy
  • Very high levels may indicate cerebral herniation
  • May be useful to indicate undiagnosed cirrhosis in patients presenting with altered mental status
  • May also be elevated in: TPN, GI Bleed and steroid use, portosytemic shunts and inborn errors of metabolism.
• B-type natriuretic peptide (BNP)
  • Released from cardiac cells in response to ventricular wall distension
  • Elevated in heart failure
  • Can be used as a diagnostic marker in patients presenting with dyspnoea to emergency department, and can be useful prognostically and to guide therapy in heart failure
  • May be elevated in many other conditions in critical care, including sepsis, acute lung injury, PE and intracranial bleed
  • Interpretation of BNP in ICU patients is therefore complex and while it may have a role in prognosis and response to therapy in future its current place is unclear.

Discussion

This question was quite arbitrarily placed into the gastroenterology section, on no grounds other than the interesting association of ammonia with various metabolic disturbances, versus the rather boring association of BNP with heart failure.

The question asks us to "critically evaluate", which means a certain systematic approach. I note that this approach was not used in the college answer.

The use of ammonia levels in critical care:

• Introduction:
  • Ammonia is a metabolic byproduct of amino acid catabolism; there has been interest in measuring ammonia levels and making attempts to associate them with various forms of pathology.
• Rationale:
  • The most prolific site of production of ammonia ions is in the gut, where amino acids are converted into ammonia by gut microflora. The ammonia is then absorbed into the portal circulation and converted into urea in the hepatic urea cycle.
  • Hepatic damage and the failure of the urea cycle is therefore usually associated with a rise in the serum ammonia levels
  • The normal compensatory responses to raised serum ammonia (eg. conversion into glutamine) can give rise to cerebral oedema and thus is thought to play some role in the pathogenesis of hepatic encephalopathy
  • Other causes of raised ammonia levels include
    • Increased rates of protein catabolism, eg. extreme starvation or hematological malignancy
    • TPN
    • Inherited errors of metabolism
• Evidence:
  • Ammonia levels in the brain and in the venous circulation do not usually correlate in stable liver disease; however there is some degree of correlation in severe hepatic encephalopathy.
  • The severity of encephalopathy does not correlate with the magnitude of ammonia elevation. Severely encephalopathic patients may have normal levels of ammonia, and patients with mild and moderate hyperammonaemia may have reasonably intact sensorium.
  •  
• Summary:
  • The use of ammonia to assess the severity of hepatic encephalopathy is still controversial
  • a raised ammonia level may point to an undiagnosed error of metabolism in a patient with an otherwise unexplainable loss of consciousness

The use of BNP levels in critical care:

• Introduction:
  • BNP is a peptide released by stressed atria which has been a tempting target of laboratory analysis in determining the aetiology of breathlessness in the acutely distressed patient
• Rationale
  • BNP (brain natriuretic peptide) is a 32-amino acid peptide released by the human atria and ventricles in response to distending pressure. In spite of its name, its presence in the human brain is rather minimal- it was first identified in porcine brain tissue, where for some reason it is concentrated. BNP is a peptide which has natriuretic and diuretic actions in the renal tubule, and is though to be a part of the natural homeostatic mechanisms which work in defence of normal intravascular volume.
  • Thus, a raised BNP, suggesting increased atrial stretch, may be a serum marker which may differentiate cardiac failure and pulmonary oedema from respiratory infection in situations when both are equally likely on the basis of history and examination.
  • The classical patient for such serology would be the elderly lady or gentleman with severe COPD and CCF, who presents to the ED with shortness of breath, wheeze, fever, and clinical features of fluid overload.
  • It may also be a useful serum marker to guide the management of heart failure
• Evidence:
  • BNP is promoted by the college answer as if it helps emergency physicians identify heart failure, but actual emergency physicians and clinical trial evidence disagree with this statement.
  • BNP is not a very good indicator of head injury
  • There is no strong evidence supporting the use of BNP in discriminating between cardiac and non-cardiac causes of respiratory failure in the critically ill patients.
  • Though a 2007 study promoted BNP as a useful way to discriminate between cardiogenic pulmonary oedema and ARDS (its elevated in ARDS, but even more elevated in APO), a later 2008 study (Yardan et al) detrmined that its sensitivity is poor
  • BNP is also elevated in sepsis, acute lung injury of any cause,  and after cardiac surgery.
  • For pulmonary embolism, BNP may be useful to identify submassive PE (which would reveal right hear tstrain though a BNP leak)- something which has both management and prognostic implications
• Summary:
  • BNP is a non-specific marker of atrial and ventricular strain, and has limited diagnostic utility. Its role in treatment monitoring and risk stratification remains to be established.

Clay, Alison S., and Bryan E. Hainline. "Hyperammonemia in the ICU." CHEST Journal 132.4 (2007): 1368-1378.

Ong, Janus P., et al. "Correlation between ammonia levels and the severity of hepatic encephalopathy." The American journal of medicine 114.3 (2003): 188-193.

McKinney, A. M., et al. "Acute hepatic (or hyperammonemic) encephalopathy: diffuse cortical injury and the significance of ammonia." American Journal of Neuroradiology 32.7 (2011): E142-E142.

Richter, Derek, and Rex MC Dawson. "The ammonia and glutamine content of the brain." Journal of Biological Chemistry 176.3 (1948): 1199-1210.

Summar, Marshall L., et al. "Unmasked adult-onset urea cycle disorders in the critical care setting." Critical care clinics 21.4 (2005): S1-S8.

Troughton, Richard W., et al. "Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations." The Lancet355.9210 (2000): 1126-1130.

McCullough, Peter A., et al. "B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure analysis from Breathing Not Properly (BNP) multinational study."  Circulation 106.4 (2002): 416-422.

Hall, Christian. "Essential biochemistry and physiology of (NT-pro) BNP."European Journal of Heart Failure 6.3 (2004): 257-260.

Silver, Marc A., et al. "BNP Consensus Panel 2004: A clinical approach for the diagnostic, prognostic, screening, treatment monitoring, and therapeutic roles of natriuretic peptides in cardiovascular diseases." Congestive Heart Failure 10.s5 (2004): 1-30.

Jefic, Dane, et al. "Utility of B-type natriuretic peptide and N-terminal pro B-type natriuretic peptide in evaluation of respiratory failure in critically ill patients."CHEST Journal 128.1 (2005): 288-295.

Karmpaliotis, Dimitri, et al. "Diagnostic and prognostic utility of brain natriuretic Peptide in subjects admitted to the ICU with hypoxic respiratory failure due to noncardiogenic and cardiogenic pulmonary edema." CHEST Journal 131.4 (2007): 964-971.

Demir, Ali, et al. "The value of Serum BNP for diagnosis of intracranial injury in minor head trauma." World journal of emergency surgery 9.1 (2014): 16.

Li, Nan, et al. "BNP and NT-proBNP levels in patients with sepsis." Ront Biosei18 (2013): 1237-1243.

Mitaka, Chieko, et al. "Increased plasma concentrations of brain natriuretic peptide in patients with acute lung injury." Journal of critical care 12.2 (1997): 66-71.

Kucher, Nils, Gert Printzen, and Samuel Z. Goldhaber. "Prognostic role of brain natriuretic peptide in acute pulmonary embolism." Circulation 107.20 (2003): 2545-2547.

Meyer, Brigitte, et al. "511: Nt-Pro-Bnp Is A Strong Predictor of Outcome in Critically Ill Patients Admitted to the Icu After Cardiac Surgery." Critical Care Medicine 39.12 (2011): 141.

Yardan, T., et al. "B-type natriuretic peptide as an indicator of right ventricular dysfunction in acute pulmonary embolism." International journal of clinical practice 62.8 (2008): 1177-1182.