My hospitalized patient with sepsis has persistently elevated lactic acid despite volume resuscitation, source control, and adequate oxygenation. What could I be missing?

Although the causes of lactic acidosis are legion (eg, sepsis, tissue hypoperfusion, ischemic bowel, malignancy, medications, liver dysfunction), thiamine deficiency (TD) is an often-overlooked cause of persistently elevated serum lactic acid (LA) in critically ill hospitalized patients,1 reported in 20-70% of septic patients.2  Septic shock patients may be particularly at risk of TD because of increased mitochondrial oxidative stress, decreased nutritional intake and presence of comorbid conditions (eg,  alcoholism, persistent vomiting).3

Early recognition of TD in hospitalized patients may be particularly difficult because of the frequent absence of the “classic” signs and symptoms of Wernicke’s encephalopathy (eg, ataxia, cranial nerve palsies and confusion) and lack of readily available confirmatory laboratory tests.4

TD-related lactic acidosis should be suspected when an elevated LA persists despite adequate treatment of its putative cause(s) (4,5). Administration of IV thiamine in this setting may result in rapid clearance of LA.3-5

TD causes lactic acidosis type B which is due to the generation of excess LA, not impairment in tissue oxygenation, as is the case for lactic acidosis type A. Thiamine is an essential co-factor in aerobic metabolism, facilitating the conversion of pyruvate to acetyl-CoA which enters the citric acid (Krebs) cycle within the mitochondria. In TD, pyruvate does not undergo aerobic metabolism and is converted to LA instead, leading to lactic acidosis.

Bonus pearl: Did you know that because of its limited tissue storage, thiamine stores may be depleted within only 3 weeks of reduced oral intake!

References

  1. O’Donnell K. Lactic acidosis: a lesser known side effect of thiamine deficiency. Practical Gastroenterol March 2017:24.   https://www.practicalgastro.com/article/176921/Lactic-Acidosis-Lesser-Known-Side-Effect-of-Thiamine-Deficiency
  2. Marik PE. Thiamine: an essential component of the metabolic resuscitation protocol. Crit Care Med 2018;46:1869-70. https://journals.lww.com/ccmjournal/Fulltext/2018/11000/Thiamine___An_Essential_Component_of_the_Metabolic.23.aspx
  3. Woolum JA, Abner EL, Kelly A, et al. Effect of thiamine administration on lactate clearance and mortality in patients with septic shock. Crit Care Med 2018;46:1747-52. https://journals.lww.com/ccmjournal/Fulltext/2018/11000/Effect_of_Thiamine_Administration_on_Lactate.5.aspx
  4. Kourouni I, Pirrotta S, Mathew J, et al. Thiamine: an underutilized agent in refractory lactic acidosis. Chest 2016; 150:247A. https://journal.chestnet.org/article/S0012-3692(16)56459-9/pdf
  5. Shah S, Wald E. Type B lactic acidosis secondary to thiamine deficiency in a child with malignancy. Pediatrics 2015; 135:e221-e224. http://pediatrics.aappublications.org/content/135/1/e221

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My hospitalized patient with sepsis has persistently elevated lactic acid despite volume resuscitation, source control, and adequate oxygenation. What could I be missing?

In my critically ill patient with infection, is capillary refill time greater than 2 seconds indicative of septic shock?

The data on the performance of capillary refill time (CRT) in adults is quite limited and what’s available does not suggest that the commonly cited 2 seconds cutoff is useful in assessing peripheral perfusion in critically ill adults1,2.

For example, a large study involving 1000 healthy adults reported that 45% of participants had a CRT > 2 seconds3.  Age also affects CRT with its 95 percentile upper limits reaching 4.5 seconds among healthy adults >60 y old3

Among patients with septic shock, a baseline median CRT of 5 seconds has been reported.  Values <5.0 seconds within 6 hours of treatment of septic shock has also been highly associated with successful resuscitation even before normalization of lactate levels4.

For these reasons, if CRT is used as a measure of peripheral perfusion in critically ill adults, a cut off of 5 seconds, not 2 seconds, may be more appropriate. But just like many other diagnostic tests, CRT should never be interpreted in isolation from other clinical parameters. 

References

  1. Lima A, Bakker J. Clinical Assessment of peripheral circulation. Critical Care 2015:21: 226-31. https://www.ncbi.nlm.nih.gov/pubmed/25827585  
  2. Lewin J, Maconochie I. Capillary refill time in adults. Emerg Med J 2008;25:325-6. https://www.ncbi.nlm.nih.gov/pubmed/18499809
  3. Anderson B, Kelly AM, Kerr D, et al. Impact of patient and environmental factors on capillary refill time in adults. Am J Emerg Med 2008;26:62-65. https://www.ncbi.nlm.nih.gov/pubmed/18082783
  4. Hernandez G, Pedreros C, Veas E, et al. Evolution of peripheral vs metabolic perfusion parameters during septic shock resuscitation. A clinical-physiologic study. J Crit Care 2012;27:283-288.  https://www.ncbi.nlm.nih.gov/pubmed/21798706
In my critically ill patient with infection, is capillary refill time greater than 2 seconds indicative of septic shock?