Impact of non-hepatic hyperammonemia on mortality in intensive care unit patients: a retrospective cohort study
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: The effect of hyperammonemia on the mortality in patients with liver cirrhosis is well documented. However, little is known about the impact of hyperammonemia on mortality among intensive care unit patients without hepatic disease. We aimed to investigate factors associated with non-hepatic hyperammonemia among intensive care unit patients and to evaluate the factors related to the 7- and 90-day mortality. Methods: Between February 2016 and February 2020, 948 patients without hepatic disease who had 972 episodes of admission to the intensive care unit were retrospectively enrolled and classified as hyperammonemia grades 0 (≤ 80 μg/dL; 585 [60.2%]), 1 (≤ 160 μg/dL; 291 [29.9%]), 2 (≤ 240 μg/dL; 55 [5.7%]), and 3 (> 240 μg/dL; 41 [4.2%]). Factors associated with hyperammonemia and the 7- and 90-day mortality were evaluated by multivariate logistic regression analysis and Cox regression analysis, respectively. Kaplan-Meier survival curves for the 7- and 90-day mortality were constructed. Results: The independent risk factors for hyperammonemia were male sex (odds ratio, 1.517), age (0.984/year), acute brain failure (2.467), acute kidney injury (1.437), prothrombin time-international normalized ratio (2.272/unit), and albumin (0.694/g/dL). The 90-day mortality rate in the entire cohort was 24.3% and gradually increased with increasing hyperammonemia grade at admission (17.9%, 28.2%, 43.6%, and 61.0% in patients with grades 0, 1, 2, and 3, respectively). Additionally, non-hepatic hyperammonemia was an independent predictor of the 90- day mortality in intensive care unit patients. Conclusions: Non-hepatic hyperammonemia is common (39.8%) and associated with the 90-day mortality among intensive care unit patients.
Abstract
Background/Aims: The effect of hyperammonemia on the mortality in patients with liver cirrhosis is well documented. However, little is known about the impact of hyperammonemia on mortality among intensive care unit patients without hepatic disease. We aimed to investigate factors associated with non-hepatic hyperammonemia among intensive care unit patients and to evaluate the factors related to the 7- and 90-day mortality. Methods: Between February 2016 and February 2020, 948 patients without hepatic disease who had 972 episodes of admission to the intensive care unit were retrospectively enrolled and classified as hyperammonemia grades 0 (≤ 80 μg/dL; 585 [60.2%]), 1 (≤ 160 μg/dL; 291 [29.9%]), 2 (≤ 240 μg/dL; 55 [5.7%]), and 3 (> 240 μg/dL; 41 [4.2%]). Factors associated with hyperammonemia and the 7- and 90-day mortality were evaluated by multivariate logistic regression analysis and Cox regression analysis, respectively. Kaplan-Meier survival curves for the 7- and 90-day mortality were constructed. Results: The independent risk factors for hyperammonemia were male sex (odds ratio, 1.517), age (0.984/year), acute brain failure (2.467), acute kidney injury (1.437), prothrombin time-international normalized ratio (2.272/unit), and albumin (0.694/g/dL). The 90-day mortality rate in the entire cohort was 24.3% and gradually increased with increasing hyperammonemia grade at admission (17.9%, 28.2%, 43.6%, and 61.0% in patients with grades 0, 1, 2, and 3, respectively). Additionally, non-hepatic hyperammonemia was an independent predictor of the 90- day mortality in intensive care unit patients. Conclusions: Non-hepatic hyperammonemia is common (39.8%) and associated with the 90-day mortality among intensive care unit patients.
참고문헌 (38)
- Laish I, "Noncirrhotic hyperammonaemic encephalopathy", Liver Int, 31, pp.1259~1270 (2011)
- Butterworth RF, "Effects of hyperammonaemia on brain function", J Inherit Metab Dis, 21(Suppl 1), pp.6~20 (1998)
- Shalimar, "Prognostic role of ammonia in patients with cirrhosis", Hepatology, 70, pp.982~994 (2019)
- Tapper EB, "Refining the ammonia hypothesis : a physiology-driven approach to the treatment of hepatic encephalopathy", Mayo Clin Proc, 90, pp.646~658 (2015)
- Jia B, "Hyperammonaemia induces hepatic injury with alteration of gene expression profiles", Liver Int, 34, pp.748~758 (2014)
- Albillos A, "Cirrhosis-associated immune dysfunction : distinctive features and clinical relevance", J Hepatol, 61, pp.1385~1396 (2014)
- Shawcross DL, "Ammonia impairs neutrophil phagocytic function in liver disease", Hepatology, 48, pp.1202~1212 (2008)
- Jalan R, "Ammonia produces pathological changes in human hepatic stellate cells and is a target for therapy of portal hypertension", J Hepatol, 64, pp.823~833 (2016)
- Cheang HK, "Hyperammonaemia due to Klebsiella infection in a neuropathic bladder", Pediatr Nephrol, 12, pp.658~659 (1998)
- Samtoy B, "Ammonia encephalopathy secondary to urinary tract infection with Proteus mirabilis", Pediatrics, 65, pp.294~297 (1980)
- Kwan L, "Hyperammonemic encephalopathy in multiple myeloma", N Engl J Med, 346, pp.1674~1675 (2002)
- Lora-Tamayo J, "Multiple myeloma and hyperammonemic encephalopathy : review of 27 cases", Clin Lymphoma Myeloma, 8, pp.363~369 (2008)
- Moffatt-Bruce SD, "Successful management of immunosuppression in a patient with severe hyperammonemia after lung transplantation", J Heart Lung Transplant, 27, pp.801~803 (2008)
- Graham TE, "Exercise-induced hyperammonemia : skeletal muscle ammonia metabolism and the peripheral and central effects", Adv Exp Med Biol, 368, pp.181~195 (1994)
- Nakamura K, "Hyperammonemia in idiopathic epileptic seizure", Am J Emerg Med, 31, pp.1486~1489 (2013)
- Seashore JH, "Hyperammonemia during total parenteral nutrition in children", JPEN J Parenter Enteral Nutr, 6, pp.114~118 (1982)
- Olde Damink SW, "Review article : hyperammonaemic and catabolic consequences of upper gastrointestinal bleeding in cirrhosis", Aliment Pharmacol Ther, 29, pp.801~810 (2009)
- Elnekave E, "Noncirrhotic extrahepatic portosystemic shunt causing adult-onset encephalopathy treated with endovascular closure", Case Rep Radiol, 2015, pp.852853~ (2015)
- Cascino GD, "Periodic hyperammonemic encephalopathy associated with a ureterosigmoidostomy", Mayo Clin Proc, 64, pp.653~656 (1989)
- Gerstner T, "Valproic acid induced encephalopathy : 19 new cases in Germany from 1994 to 2003 : a side effect associated to VPA-therapy not only in young children", Seizure, 15, pp.443~448 (2006)
- Ambrosetto G, "Hyperammonemia in asterixis induced by carbamazepine : two case reports", Acta Neurol Scand, 69, pp.186~189 (1984)
- Batshaw ML, "Treatment of hyperammonemic coma caused by inborn errors of urea synthesis", J Pediatr, 97, pp.893~900 (1980)
- Hawkes ND, "Non-hepatic hyperammonaemia : an important, potentially reversible cause of encephalopathy", Postgrad Med J, 77, pp.717~722 (2001)
- Sakusic A, "Features of adult hyperammonemia not due to liver failure in the ICU", Crit Care Med, 46, pp.e897~e903 (2018)
- Clay AS, "Hyperammonemia in the ICU", Chest, 132, pp.1368~1378 (2007)
- Prado FA, "Hyperammonemia in ICU patients : a frequent finding associated with high mortality", J Hepatol, 62, pp.1216~1218 (2015)
- Khwaja A, "KDIGO clinical practice guidelines for acute kidney injury", Nephron Clin Pract, 120, pp.c179~c184 (2012)
- Reddy DR, "Identification of acute brain failure using electronic medical records", J Crit Care, 34, pp.12~16 (2016)
- Bachmann C, "Mechanisms of hyperammonemia", Clin Chem Lab Med, 40, pp.653~662 (2002)
- Olde Damink SW, "Kidney plays a major role in ammonia homeostasis after portasystemic shunting in patients with cirrhosis", Am J Physiol Gastrointest Liver Physiol, 291, pp.G189~G194 (2006)
- Olde Damink SW, "Upper gastrointestinal bleeding : an ammoniagenic and catabolic event due to the total absence of isoleucine in the haemoglobin molecule", Med Hypotheses, 52, pp.515~519 (1999)
- Lee JC, "Hyperammonemic encephalopathy due to essential amino acid hyperalimentation", J Formos Med Assoc, 93, pp.486~491 (1994)
- Murphy JV, "Asymptomatic hyperammonemia in patients receiving v alproic acid", Arch Neurol, 39, pp.591~592 (1982)
- Maldonado C, "Carnitine and", or acetylcarnitine deficiency as a cause of higher levels of ammonia, 2016, pp.2016, 2920108~
- Ong JP, "Correlation between ammonia levels and the severity of hepatic encephalopathy", Am J Med, 114, pp.188~193 (2003)
- Hermenegildo C, "Activation of N-methyl-D-aspartate receptors in rat brain in vivo following acute ammonia intoxication : characterization by in vivo brain microdialysis", Hepatology, 31, pp.709~715 (2000)
- Ahluwalia V, "Impaired gut-liver-brain axis in patients with cirrhosis", Sci Rep, 6, pp.26800~ (2016)
- Clemmesen JO, "Cerebral herniation in patients with acute liver failure is correlated with arterial ammonia concentration", Hepatology, 29, pp.648~653 (1999)