Early ICU Nutritional Support Reduces Liver Dysfunction

MADRID, Jan. 29 -- Starting nutrition support early but at a limited energy requirement may protect against liver dysfunction for intensive care patients with sepsis, according to a large cohort study here.

Parenteral or enteral feeding started within the first 24 hours but kept below 25 kcal/kg per day were associated with significantly less liver dysfunction (P<0.01 and P=0.03, respectively), reported Teodoro Grau, M.D., of the Hospital Severo Ochoa here, and colleagues, online in Critical Care.

Artificial nutrition has been found to cause liver dysfunction as a complication in a quarter to 100% of ICU cases. The exact reason is not known though sepsis and inflammation can increase the production of cytokines that inhibit bile secretion and consequently cause cholestasis.

The findings have important implications in preventing long-term damage for patients, the researchers said.

"Interestingly, our data show that the early use of artificial nutrition?can delay the appearance of any type of [liver dysfunction] and can avoid permanent liver damage in these patients," the researchers wrote.

Total parenteral nutrition, administered through a central venous catheter, is known to increase the risk more than enteral feeding.

The study of 725 critically ill patients treated at 40 intensive care units in Spain found this difference as well (P<0.001). However, the greatest risk for developing liver dysfunction was seen with sepsis, multiple organ failure, and total parental nutrition.

"Notwithstanding prevention and treatment measures," the authors wrote, "the presence of sepsis and multiple organ failure should compel to clinicians to strictly control the caloric intake of seriously ill patients, start artificial nutrition early, and frequently monitor their liver function."

The study prospectively monitored liver dysfunction in consecutively enrolled adults who were expected to need artificial nutrition during five or more days in the intensive care unit. Patients were followed until hospital discharge or for 28 days.

Patients were fed according to physician preference with early artificial nutrition recommended via the enteral route if the patient's gastrointestinal system was preserved. More patients received enteral than total parenteral nutrition (422 and 303, respectively). Both groups typically started nutrition within a day of admission and continued for a median of nine days.

Liver dysfunction was defined as cholestasis, liver necrosis or a mixed pattern with liver function measures 10% above normal reference laboratory values. Overall, 23% of patients developed liver dysfunction (30% in the total parenteral nutrition group and 18% in the enteral group).

In the multivariate analysis, the factors significantly associated with development of liver dysfunction were:

• Total parenteral nutrition (OR 1.96, 95% CI 1.3 to 2.97, P<0.001),
• Use of artificial nutrition within 24 hours of admission (OR 0.6, 95% CI 0.4 to 0.9, P<0.01),
• Multiple Organ Dysfunction Score at admission (OR 1.1, 95% CI 1.04 to 1.2, P<0.001),
• Sepsis diagnosis at admission (OR 1.76, 95% CI 1.08 to 2.9, P<0.02),
• Energy requirements less than 25 kcal/kg per day (OR 0.62, 95% CI 0.41 to 0.94, P=0.03), and
• Mechanical ventilation (OR 0.5, 95% CI 0.3 to 1.07, P=0.05).

These differences resulted in longer intensive care stays but not higher mortality rates.

Patients who received enteral nutrition typically had a longer stay than those who received parenteral nutrition (mean 12 versus eight days, P<0.001), but 28-day mortality was not significantly different between groups.

Likewise, patients who developed liver dysfunction had longer stays in the ICU (16 versus nine days, P<0.001) and in the hospital (28 versus 23 days, P<0.01). There was no difference in mortality compared to those without liver dysfunction though (28.3% versus 28.1%, P=0.9).

The researchers found important differences between patients given the two types of artificial nutrition. Those who received TPN were older (66 versus 61, P<0.01), more likely to be female (38% versus 29%, P<0.05), and more likely to be surgical patients (P<0.001).

TPN was also more likely to be used for patients who were admitted with sepsis or septic shock but fewer of those who required mechanical ventilation (P<0.001).