Journal of Parenteral and Enteral Nutrition: Early Enteral Feedings in Adults Receiving Venovenous Extracorporeal Membrane Oxygenation

Early Enteral Feedings in Adults Receiving Venovenous Extracorporeal Membrane Oxygenation

Scott, L Keith

ABSTRACT. Introduction: For over 20 years extracorporeal membrane oxygenation (ECMO) has been an advanced treatment for adults, children and neonates with severe respiratory failure that has failed to respond or improve with conventional therapy. Withholding enteral feeding in patients on ECMO is common practice in many centers, based partly on the risk of splanchnic ischemia resulting in loss of intestinal integrity, predisposing to bacterial translocation and sepsis. We report one center’s experience with early enteral nutrition in adult patients receiving venovenous (VV) ECMO for severe respiratory failure. Methods: Adult patients that received VV ECMO at LSUHSC-Shreveport over the last 8 years were eligible for inclusion. Results: A total of 27 patients met these criteria and their charts and nutrition therapy reviewed. Average duration of ECMO support was 8.7 ± 3.6 days. Twenty-six of 27 (96%) received enteral nutrition via gastric tube alone or in combination with total parenteral nutrition (TPN). Eighteen patients received enteral nutrition as their only source of nutritional supplementation, with the remainder receiving partial nutrition support via the parenteral route. Seventy-five percent of the patients received prokinetic medication within the first 24 hours, with 95% receiving prokinetic therapy by 48 hours. No patients developed intestinal ischemia, gastrointestinal bleeding, or other complications related to early enteral feeding. Conclusion: Enteral nutrition started within the first 24 to 36 hours of initiating venovenous ECMO support is safe and well-tolerated in adults. No serious adverse events were attributable to enteral nutrition in these patients. (Journal of Parenteral and Enteral Nutrition 28:295-300, 2004)

Extracorporeal membrane oxygenation (ECMO) has been used for the past 3 decades in the support of patients with severe cardiopulmonary failure unresponsive to conventional therapies. The most widespread application of ECMO has been in the support of severe respiratory failure in the neonate, with over 18,000 cases reported to the registry of the Extracorporeal Life Support Organization (ELSO).1 Application of ECMO in the pediatric, and more recently the adult population has continued to grow.

The application of ECMO involves an extracorporeal circuit applied in 1 of 2 cannulation configurations with differing effects on the cardiovascular system. The extracorporeal circuit is similar for both modes, consisting of a venous drainage cannula, reservoir, blood pump, membrane or hollow fiber oxygenator, heat exchanger, and return cannula. Patients with severe cardiac dysfunction complicating respiratory failure typically are placed on venoarterial (VA) ECMO, in which blood is drained from the central venous system (right atrium) and returned after oxygenation to the central arterial circulation (eg, the aortic root via the right carotid artery). This mode provides partial to complete bypass of the pulmonary circulation and provides circulatory support in addition to gas exchange. Patients with primarily respiratory failure are candidates for venovenous (VV) ECMO, in which blood is drained from the central venous system and returned after oxygenation back to the central venous circulation. Blood entering the pulmonary circulation is preoxygenated, but no circulatory support is provided, and native cardiac function is required for maintaining cardiac output. Venovenous support is applied whenever possible because arterial cannulation is avoided, but patients are at risk for organ ischemia if cardiac function deteriorates. Patients on W support often have some degree of circulatory dysfunction requiring inotropic support.

The adult and pediatric population receiving ECMO differs from the neonatal population because of the high frequency of associated multiple organ dysfunction in these older patients. Because of the severity of illness and multiple other complications, many centers are reluctant to feed non-neonatal patients enterally despite the observation that enterai nutrition in the critically ill has consistently shown benefit, not only in standard nutritional parameters but also with respect to improved survival.

The safety of enteral feedings has been demonstrated in both pediatric and neonatal patients supported with ECMO, but nutrition therapy of adult patients on ECMO has not been evaluated. In the adult population, withholding enterai feeding in patients on ECMO is common practice in many centers.2 It is based partly on the belief that enterai nutrition can worsen splanchnic ischemia,3 resulting in loss of intestinal integrity and predisposing to bacterial translocation, sepsis, and multi-organ failure.

We evaluated our center’s experience with early enterai nutrition in adult patients receiving VV ECMO for severe respiratory failure in order to characterize the safety and tolerance of enteral nutrition in this patient population.

METHODS

This study is a retrospective, uncontrolled case series of adult patients undergoing VV ECMO for severe respiratory failure. The study protocol was reviewed by the Institutional Review Board of Louisiana State University Health Sciences Center and was granted exemption status.

Subject Selection

Subjects were identified from the institutions registry of ECMO patients. Subjects were included with the following criteria: age > or =18 years, support with venovenous ECMO for acute respiratory failure, and duration of support >48 hours.

Patients with

Management on ECMO

Patients supported with ECMO were managed similarly to non-ECMO patients with organ failure, with the exception of ventilator management. Once gas exchange was established with ECMO, the ventilator was changed to low-frequency (rate 5), low tidal volume (5-7 mL/kg), pressure-controlled ventilation. In most patients this was transitioned to pressure support ventilation within 24 hours. Patients underwent diuresis or ultrafiltration to dry weight. Serum oncotic pressure was maintained by targeting a total protein above 5.2 g/dL, with infusion of 25% albumin as required. Renal dysfunction was managed with continuous renal replacement therapy connected into the ECMO circuit.

Vasoactive agents used included dobutamine and norepinephrine, alone or in combination, based on preECMO measurement of hemodynamics by pulmonary artery catheter (if present) or transthoracic echocardiography. Dopamine was avoided when possible due to its potentially deleterious effects, including gastrointestinal dysfunction.4 Vasoactive agents were reduced as cardiovascular function improved after initiation of ECMO.

Nutrition Support Protocol

Patients on ECMO support were provided enteral nutrition according to the same protocol for non-ECMO patients in our institution’s medical ICU. Commercial oligomeric nutritional formulas were used in all cases. The first 16 patients received non-enhanced formulas (Reabilan, Nestlé S.A., Glendale, CA). After our adoption of immune-modifying formulas,5-8 the remaining 11 patients received arginine- and glutamine-enhanced immune-modifyng formulas (Impact with Glutamine, Norvartis Nutrition or Crucial, Nestlé S.A.). Target caloric goals were 25 kcal/kg/d with protein targeted at 1.2 to 1.5 g/kg/d. Feeding was withheld during initiation of ECMO until the subjects had stable hemodynamics and gas exchange (typically 12 to 24 hours). Enteral feeding was initiated as continuous intragastric feeding at 20 mL/h via a 16 or 18 Fr nasogastric tube, increasing the rate of delivery every 4 hours over 24 to 36 hours to the target rate. To reduce the risk of pulmonary aspiration,9 gastric residuals were measured every 4 hours, and volumes

Tolerance of nutrition support was defined as the percentage of the volume of delivered enteral formula that was retained over 24 hours (ie, infused and not discarded due to elevated gastric residuals). Parenteral nutrition (PN) was initiated if tolerance of enteral support fell below 50% over a 24-hour period. The caloric goal for PN was the difference between target caloric goal and enteral caloric intake. PN was discontinued when enteral tolerance exceeded 75% for at least 24 hours.

Serious adverse events related to enteral nutrition are defined as pulmonary aspiration, nosocomial pneumonia, and abdominal complications. Pulmonary aspiration was defined as an identifiable event; documenting the presence of tube feeding in the tracheobronchial tree, with or without worsening of pulmonary infiltrates. Nosocomial pneumonia was defined as development of new pulmonary infiltrates, purulent tracheobronchial secretions, and systemic evidence of infection including new or recurrent fever and leukocytosis. Abdominal complications included adynamic or obstructive ileus, perforation, or abdominal sepsis.

Data Analysis

Data were extracted from the medical records by a registered dietitian (K.B.) and a critical care physician (F.T.) under the oversight of an ECMO physician (L.K.S.). These data were entered into a statistical analysis program (S-Plus version 6.2, Insightful Corporation, Seattle, WA) for data analysis and presentation. Descriptive statistics included calculation of means ± SE for parametric data, and calculation of percentages for frequency data. Comparison of data at different individual time points was performed using analysis of variance (ANOVA), with the Bonferroni method for multiple comparisons. Trends over time were tested using linear regression analysis. Data analysis procedures and results were reviewed by a biostatistician.

RESULTS

A total of 27 patients met this criterion and their charts and nutrition therapy reviewed. Average duration of ECMO support was 8.7 ± 3.6 days. Twenty-six of 27 (96%) received enteral nutrition as the sole means of support or in combination with PN. Twenty-five of the 26 patients receiving enteral or combined enteral and PN support were initiated within 24 hours of the institution of ECMO. Eighteen patients received enteral nutrition as their only source of nutritional supplementation, with the 8 receiving partial PN support. Only 1 patient received PN as their only source of nutrition support.

All but 2 patients received enteral nutrition within 24 hours of initiating ECMO and all patients received enteral feedings by 36 hours. Seventy-five percent of the patients received prokinetic medications within the first 24 hours, with 95% receiving prokinetic therapy by 48 hours.

Figure 1 demonstrates the percentage of caloric goal given and the percentage of tolerance. On day 1, the target delivery rate was 27%, but increased to 60% of their nutritional goal by the second day. By day 3, patients were receiving 74% of nutritional goal, and by 1 week >80% was achieved and sustained. These increases were significantly increased from baseline from day 2 onward (p = .004 by ANOVA).

Tolerance of delivered feedings reached 80% by day 2 (Fig. 2). Tolerances remained stable throughout the ECMO run after the first day. There was no difference in tolerances throughout the ECMO course (p = .323 by ANOVA).

Nutritional parameters were not performed routinely. Indirect calorimetry was not performed due to the difficulty in measuring gas exchange of the extracorporeal circuit. Figure 3 shows the mean serum albumin levels on the patients on extracorporeal life support. The initial rise in albumin concentration is most likely due to our aggressive support of plasma oncotic pressure through the administration of supplemental albumin. The trend of increasing albumin levels over the ECMO course was statistically significant (p

Adverse Events

No serious adverse events as defined above that could be related to enterai nutrition were noted. Specifically, no documented cases of pulmonary aspiration, nosocomial pneumonia, and abdominal complications were identified.

DISCUSSION

The potential benefits of early enteral nutrition intervention in the critically ill have been increasingly recognized over the past several years.13-15 Our increased understanding of the immunologic contribution of the gastrointestinal tract to host defenses in the critically ill is under renewed investigation.16 Still, numerous questions remain unanswered. For example, recent data suggest nutrition with immune-enhancing formulas has improved outcomes in the critically ill17,18; however, the data are conflicting and open to considerable debate.19 A recent systematic review supported a Class B recommendation.20

Our protocol for gastric feeding (150 mL residual limit, and selective use of a prokinetic agent) may be conservative. Pinilla et al21 compared a similar protocol with one allowing for up to 250 mL limit with mandatory prokinetic agents, and found a higher tolerance with the latter regimen. Although the tolerance of enteral feeding in our patients was high, it is possible we could have achieved a higher success with this more aggressive regimen.

Tolerance of enteral feedings may be affected by decreases in serum oncotic pressure.22 Our protocol for management of patients on ECMO includes diuresis or hemofiltration to dry weight, minimizing edema, with the use of albumin to maintain intravascular volume and serum oncotic pressure (based on total protein measurements). This approach may have contributed to the high tolerance of enteral feeding in our patients, but our study design did not allow us to address it.

Time of feeding in patients with circulatory compromise is also controversial.3 Although we initiated feeding early, usually within 24 hours, we did not initiate feeding during hemodynamic instability. The institution of venovenous ECMO, however, is typically associated with improvement in hemodynamics, most likely due to improved myocardial oxygenation and contractility, and marked reduction in intrathoracic pressures with improvement of both right and left ventricular function. Although it has been suggested that patients on vasoactive drug support and sedation should not be fed enterally,23 our experience suggests otherwise, at least with ECMO support.

We identified no serious adverse events of pulmonary aspiration or nosocomial pneumonia. Our feeding protocol provides for continuous monitoring for intolerance of feeding and patient positioning mirroring the recommendations provided by McClave et al.24 Detection of aspiration events is difficult.25 Although we did not identify any aspiration events clinically, subclinical aspiration may have occurred; however, these did not result in clinically identifiable syndromes.

There is limited data on enterai feeding in the pediatric and neonatal populations. One center reported their experience in 29 consecutive pediatric patients who required ECMO.26 One group consisted of patients who were provided nutrition support using TPN whereas the other group was provided total enteral nutrition during ECMO. Both groups were similar in age, weight, pre-ECMO oxygenation index, alveolararterial oxygen difference, type, and duration of ECMO. There was no difference between the 2 groups in the time needed to achieve caloric goal and no complications were associated with the utilization of enteral feedings. The authors concluded that enteral nutrition in patients receiving either venoarterial or venovenous ECMO is well-tolerated, provides adequate nutrition, and is without complications, compared with PN.

The neonatal experience is similar. One prospective study compared septic complications between enterally fed and parenterally fed neonates that required ECMO support.27 Enteral nutrition did not influence the risk of sepsis in neonates on ECMO when compared with TPN. Furthermore, enteral nutrition was well-tolerated and not associated with adverse effects. Additional data on intestinal integrity in newborns supported on ECMO suggest a risk of compromise in mucosal blood flow; however, the introduction of enteral nutrition did not result in deterioration or change in clinical state.28 Therefore, the limited clinical data does not support the practice of withholding enteral nutrition in critically ill newborns on ECMO.

Data on early enterai feeding in adults on ECMO are lacking. Anderson et al29 reported a series of adult trauma patients supported with ECMO, in which enteral feeding was attempted, but not tolerated. Kolla et al30 presented their experience with 100 adult patients supported with ECMO for severe respiratory failure. The description of the management protocol included early enteral nutrition, or PN if the enteral route was not possible, but they did not describe their success, tolerance, or complications.

This retrospective evaluation of a single center experience demonstrates that adult patients undergoing venovenous ECMO tolerate enteral feedings without identifiable complications. It appears reasonable that patients on ECMO, although unique, have nutritional requirements and tolerance issues consistent with other critically ill patients such as those with septic shock or severe ARDS who are not on ECMO. Therefore, extrapolating data from other ICU nutrition studies and practices, and applying them to the ECMO population, appears rational.

CONCLUSION

Initiation of enteral feeds within the first 24 hours of instituting venovenous ECMO in adult patients with severe respiratory failure was safe and well tolerated. All but 1 patient in our series received enteral nutrition. Enteral nutrition provided over 75% of nutritional intake after the first 2 days. The gastric route was successful in all but 1 patient. Prokinetic agents were frequently employed, perhaps contributing to tolerance of gastric feeding. No serious adverse events were attributable to enteric nutrition.

ACKNOWLEDGMENTS

The authors extend their appreciation to Gloria Caldito, PhD for her assistance with the statistical analysis procedures. This work was supported by the Division of Critical Care Research, Departments of Medicine and Emergency Medicine, LSU Health Sciences Center, Shreveport, LA, USA.

REFERENCES

1. Conrad SA, Rycus PT. Extracorporeal life support 1997. ASAIO J. 1998;44:848-852.

2. Torosian MB, Bastawrous A, Statter M, Arensman R. Management of children with ECLS. In: Zwischenberger JB, Bartlett RH, eds. ECMO: Extracorporeal Cardiopulmonary Life Support. Ann Arbor, MI: Extracorpeal Life Support Organization; 1995: 361.

3. Rokyta R, Jr., Matejovic M, Krouzecky A, Novak I. Enteral nutrition and hepatosplanchnic region in critically ill patients-friends or foes? Physiol Res. 2003;52:31-37.

4. Dive A, Foret F, Jamart J, Bulpa P, Installe E. Effect of dopamine on gastrointestinal motility during critical illness. Intensive Care Med. 2000;26:901-907.

5. Garcia-de-Lorenzo A, Zarazaga A, Garcia-Luna PP, et al. Clinical evidence for enteral nutritional support with glutamine: a systematic review. Nutrition. 2003;19:805-811.

6. Conejero R, Bonet A, Grau T, et al. Effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity at 28 days in critically ill patients with systemic inflammatory response syndrome: a randomized, single-blind, prospective, multicenter study. Nutrition. 2002;18:716-721.

7. Grimm H, Kraus A. Immunonutrition-supplementary amino acids and fatty acids ameliorate immune deficiency in critically ill patients. Langenbecks Arch Surg. 2001;386:369-376.

8. Heyland DK, Novak F, Drover JW, Jain M, Su X, Suchner U. Should immunonutrition become routine in critically ill patients? A systematic review of the evidence. JAMA. 2001;286:944-953.

9. Mentec H, Dupont H, Bocchetti M, Cani P, Ponche F, Bleichner G. Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications. Crit Care Med. 2001;29:1955-1961.

10. Boivin MA, Levy H. Gastric feeding with erythromycin is equivalent to transpyloric feeding in the critically ill. Crit Care Med. 2001;29:1916-1919.

11. Berne JD, Norwood SH, McAuley CE, et al. Erythromycin reduces delayed gastric emptying in critically ill trauma patients: a randomized, controlled trial. J Trauma. 2002;53:422-425.

12. van der Voort PH, Zandstra DF. Enteral feeding in the critically ill: comparison between the supine and prone positions: a prospective crossover study in mechanically ventilated patients. Crit Care. 2001;5:216-220.

13. Hadfield RJ, Sinclair DG, Houldsworth PE, Evans TW. Effects of enteral and pareriteral nutrition on gut mucosal permeability in the critically ill. Am J Respir Crit Care Med. 1995;152:1545-1548.

14. Kudsk KA. Early enteral nutrition in surgical patients. Nutrition. 1998;14:541-544.

15. Vincent JL, Preiser JC. Management of the critically ill patient with severe sepsis. J Chemother. 1999;11:524-529.

16. Schmidt H, Martindale R. The gastrointestinal tract in critical illness: nutritional implications. Curr Opin Clin Nutr Metab Care. 2003;6:587-591.

17. Bower RH, Cerra FB, Bershadsky B, et al. Early enteral administration of a formula (Impact) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: results of a multicenter, prospective, randomized, clinical trial. Crit Care Med. 1995;23:436-449.

18. Suchner U, Kuhn KS, Furst P. The scientific basis of immunonutrition. Proc Nutr Soc. 2000;59:553-563.

19. Mendez C, Jurkovich GJ, Garcia I, Davis D, Parker A, Maier RV. Effects of an immune-enhancing diet in critically injured patients. J Trauma. 1997;42:933-940.

20. Montejo JC, Zarazaga A, Lopez-Martinez J, et al. Immunonutrition in the intensive care unit. A systematic review and consensus statement. Clin Nutr. 2003;22:221-233.

21. Pinilla JC, Samphire J, Arnold C, Liu L, Thiessen B. Comparison of gastrointestinal tolerance to two enterai feeding protocols in critically ill patients: a prospective, randomized controlled trial. JPEN J Parenter Enteral Nutr. 2001;25:81-86.

22. Hwang TL, Lue MC, Nee YJ, Jan YY, Chen MF. The incidence of diarrhea in patients with hypoalbuminemia due to acute or chronic malnutrition during enteral feeding. Am J Gastroenterol. 1994;89:376-378.

23. Spain DA. When is the seriously ill patient ready to be fed? JPEN J Parenter Enterai Nutr. 2002;26(Suppl):S62-S65.

24. McClave SA, DeMeo MT, DeLegge MH, et al. North American Summit on Aspiration in the Critically 111 Patient: consensus statement. JPEN J Parenter Enteral Nutr. 2002;26(Suppl):S80-S85.

25. Maloney JP, Ryan TA. Detection of aspiration in enterally fed patients: a requiem for bedside monitors of aspiration. JPEN J Parenter Enteral Nutr. 2002;26(Suppl):S34-S41.

26. Pettignano R, Heard M, Davis R, Labuz M, Hart M. Total enteral nutrition versus total parenteral nutrition during pediatric extracorporeal membrane oxygenation. Crit Care Med. 1998;26:358-363.

27. Wertheim HF, Albers MJ, Piena-Spoel M, Tibboel D. The incidence of septic complications in newborns on extracorporeal membrane oxygenation is not affected by feeding route. J Pediatr Surg. 2001;36:1485-1489.

28. Piena M, Albers MJ, Van Haard PM, Gischler S, Tibboel D. Introduction of enteral feeding in neonates on extracorporeal membrane oxygenation after evaluation of intestinal permeability changes. J Pediatr Surg. 1998;33:30-34.

29. Anderson HL, III, Shapiro MB, Delius RE, Steimle CN, Chapman RA, Bartlett RH. Extracorporeal life support for respiratory failure after multiple trauma. J Trauma. 1994;37:266-272.

30. Kolla S, Awad SS, Rich PB, Schreiner RJ, Hirschl RB, Bartlett RH. Extracorporeal life support for 100 adult patients with severe respiratory failure. Ann Surg. 1997;226:544-564.

L. Keith Scott, MD*[dagger]; Karla Boudreaux, RD, MS[double dagger]; Faisal Thaljeh, MD*; Laurie R. Grier, MD*[dagger]; Steven A. Conrad, MD, PhD, CNSP*[dagger]

* Department of Medicine, Division of Critical Care Medicine, [dagger] Department of Emergency Medicine, [double dagger] Nutritional Support Service, Extracorporeal Life Support Program, Louisiana State University Health Sciences Center, Shreveport, Louisiana

Received for publication, March 26, 2004.

Accepted for publication, June 8, 2004.

Correspondence: L. Keith Scott, MD, Louisiana State University Health Sciences Center, 1541 Kings Highway, P.O. Box 33932, Shreveport, LA 71130-3932. Electronic mail may be sent to lscott2@lsuhsc.edu.

Copyright American Society for Parenteral and Enteral Nutrition Sep/Oct 2004

Provided by ProQuest Information and Learning Company. All rights Reserved