Safety And Effectiveness Of Enteral Nutrition In Critically Ill Patients With Hemodynamic Instability

Objective: Nutritional support is an essential component in critical care. Evidence suggests that in patients with a functional gut, nutrition should be administered through the enteral route, largely because of the morbidity associated with other routes of feeding. In critically ill patients without severe sepsis, compared with enteral nutrition(EN), parenteral nutrition(PN) results in longer ICU stays and a greater chance that severe sepsis or septic shock will develop. Other favorable effects of enteral nutrition include better substrate utilization, prevention of mucosal atrophy, preservation of the integrity of gut flora,and preservation of immunocompetence. In 2009, the Society of Critical Care Medicine(SCCM) and the American Society for Parenteral and Enteral Nutrition(A.S.P.E.N.) guidelines for the provision and assessment of nutrition support therapy recommended EN may beging within the first 24–48 hours following admission to an intensive care unit(ICU) once resuscitation and hemodynamic stability have been achieved. Although it is recommended that EN be withheld in patients requiring significant hemodynamic support, including highdose catecholamine agents which could reduce EN tolerance,the definition of “high-dose” catecholamine agents has not been not made in this setting. There is considerable controversy regarding the use of EN in patients requiring IV vasopressor support. Administration of catecholamine therapy has been associated with reduced EN tolerance.Splanchnic perfusion is reduced in sepsis and shock, yet vasoactive agents have demonstrated both improved and diminished perfusion.Inadequate perfusion increases the risk of experiencing rare but serious adverse events such as mesenteric ischemia and bowel perforation even non-occlusive bowel necrosis(NOBN). There is considerable controversy regarding the use of EN in patients requiring IV vasopressor support. This study is to evaluate whether the EN is safe for critically ill patients with hemodynamic instability and provide theoretical basis for the administration of EN.Method: A prospective medical record review was conducted in the ICU of People Hospital of He Bei Province(18 licensed beds) and collected patients who received concomitant EN and IV(intravenous) vasopressor therapy from March 2013 to October 2014. Patients could be included more than once in the study if more than 1 episode of concomitant EN and IV vasopressor therapy occurred during the hospital admission. If an interruption of IV vasopressor therapy occurred for ≥24 hours, any subsequent resumption of concomitant administration was counted as a second episode for that patient. The time of initiation EN was that the patients admission to ICU received full resuscitation and no longer required a lot of rehydration, as well as vasopressor dose began to cut, vasopressor and EN must overlap more than 24 hours. The safety and effectiveness of EN was evaluated through the observation of EN tolerance and paracetamol absorption test. EN tolerance was defined as an absence of gastric residuals ≥300 m L, nausea,emesis, positive finding on abdominal imaging(x-ray), and evidence of bowel contents by abdominocentesis. Moreover, 12 patients were collected to join in the acetaminophen absorption test to evaluate the EN absorption. Basing on whether receiving IV vasopressor,12 patients were divided into experimental group and control group, the thearapy of patients in the two groups was similar in addition to vasopressor. Giving acetaminophen 0.5 g through the nasogastric tube and using the high-performance liquid chromatography(HPLC) measured before and(10,20, 30, 60, 90, 120, 150,180,240,360 and 600) minutes to measure the plasma concentration.Pharmacokinetic parameters such as the area under plasma concentration-time curve(AUC), the maximum plasma concentration(Cmax) and the time to maximum plasma concentration(Tmax) were derived, using DAS3.2.7 statistcal program to analyze the data and using the atrioventricular model to analyze the pharmacokinetic parameters.EN data were analyzed using SPSS13.0 statistcal program. Normally distributed continuous data were described using x-±s, whereas nonnormally distributed continuous data were described with median(interquartile range [IQR]). Comparison between the two sample mean used a 2-sample Student test or nonparametric test. Enumeration data were analyzed using the χ2 test or Fisher,s exact test.Results:1 General information: A total of 100 patients were included with a total of 140 overlap episodes including 113 cases men and 27 cases women. Of the 140 overlap episodes, there were 117 cases(83.6% vs 16.4%) of EN tolerance compared with EN non-tolerance.The etiology resulting into hemodynamic instability were septic shock(80.3%vs73.9%), cardiac function obstacle caused by sepsis(6% vs 8.7%),hypovolemic shock(6% vs 8.7%)and cardiogenic shock(4.3%vs4.3%). There was no statistical difference in age, gender, weight, MAP and APACHEII scores admission to ICU(P>0.05).2 The tolerance of EN: The median duration of overlap was significantly shorter in the group that tolerated EN(90 hours vs 120 hours, P= 0.017). In addition, the mean caloric intake was higher in the group that had objective tolerability(20 kcal/kg/d vs 16 kcal/kg/d, P<0.001). Percent goal nutrition was higher in the group that had objective tolerability(65% vs 51%, P<0.002).Patients who tolerated EN were less likely to be prescribed promotility agents(15.0% vs 44.0%, P<0.001).3 Vasopressor and EN:The vasopressor was norepinephrine,secondly dopamine and epinephrine. An inverse relationship was found between norepinephrine dose and EN tolerability More than 80% of the patients could tolerate EN when norepinephrine dose was less than 1 ug/kg/min, about 60% of patients could tolerate EN as dose of norepinephrine in 1 ~ 1.5 ug/kg/min.However, less 40% of the patients could tolerate EN while norepinephrine dose was higher than 1.5 ug/kg/min. Patients who tolerated EN were less likely to have received dopamine(78.6% vs 84.1%, P=0.015),it had no correlation with the dose.There was no significant difference in whether receiving norepinephrine and epinephrine(P>0.05). Patients who tolerated EN were less likely to experience a rise in serum lactate compared with those who did not tolerate EN(43.6% vs91.3%, P<0.001), the rising lactate >2 mmol/L and the maximum lactate(median, 2 mmol/L vs 3.9mmol/L, P=0.001) in the two groups had a statistically significant.4 Complications of EN: One or more episodes of emesis occurred in 18(12.9%),the percent of in EN toleronce and EN not-toleronce was 6.8%and 43.5%,respectively. High gastric residuals(≥300 m L) occurred in 14(10%) overlap episodes, the percent of in EN toleronce and EN not-toleronce was 5.1%and 34.8%,respectively. Abdominal imaging(x-ray) or abdominocentesis was performed in 12.1% and 8.6% of cases, respectively, the percent of patients who performed abdominal imaging(x-ray) in EN toleronce and EN not-toleronce was 23.5% and 76.5%.We considered presence of bowel perforation on abdominal imaging(x-ray) and intestinal content through abdomi nocentesis to be positive findings,there had no positive findings in both EN toleronce and EN not-toleronce.5 Acetaminophen absorption test:Collecting 12 patients to participate the paracetamol absorption experiment, 6 patients whose vasopressor does was relatively stable from EN tolerance group were regarded as experimental group, and the other 6 patients from ICU for the same period whose therapy was similaray with the experimental group in addition to not using vasopressor were regarded as control group.The AUC showed that Tmax of experimental group was longer compared with control group(40±15.4 min vs 30±10.68 min),however, there was no significant difference in pharmacokinetic parameters(AUC240, Cmax and Tmax) and plasma concentration in each time(P>0.05). The norepinephrine dose in experimental group was under 0.3ug/kg/min.Conclusion: EN is relatively well tolerated in patients receiving IV vasopressor support under 1.0 ug/kg/min of norepinephrine,and the percent of tolerance is about 80%. Tolerability was less likely in patients receiving a dose above 1.0 ug/kg/min of IV norepinephrine and in those receiving dopamine. These patients should be monitored more closely for signs of intolerance. The critical ill patients with hemodynamic instability preserve some gastric emptying and small intestine absorption function, A small norepinephrine dose has no significant effects on EN absorption..