Download Running head: SAFETY OF ENTERAL NUTRITION AND

Running head: SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
Safety of Enteral Nutrition and Vasoactive Agents
Leah Fite
Wright State University
1
SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
2
Safety of Enteral Nutrition and Vasoactive Agents
Significance of the Problem
Nutritional support in critically ill patients is an important adjunctive therapy proven to
decrease the incidence of morbidity, mortality, and length of stay. Early enteral nutrition (EEN),
particularly within the first 24 to 48 hours of admission to the intensive care unit (ICU) once
hemodynamic stability and fluid resuscitation has been achieved, provides the most benefits on
patient outcomes (McClave et al., 2009). Enteral nutrition (EN) is preferred to parenteral
nutrition (PN) due to the preservation of immunocompetence and integrity of gut flora, and
decreased risk for infection (Turza, Kenitsky, & Sawyer, 2009).
Many patients in the ICU maintain a tenuous, hemodynamically unstable state, requiring
the use of intravenous (IV) vasoactive agents, and the problem arises as to when it is safe to
initiate or continue EN in these patients in order to decrease the incidence of adverse outcomes
related to decreased splanchnic perfusion and mesenteric ischemia, but also provide the best
outcomes. Clinical guidelines offer recommendations for the initiation of enteral feeding for the
critically ill, hemodynamically stable patient, however, in the hemodynamically unstable patient
requiring significant vasopressor support, withholding EN is a grade E recommendation
(McClave et al., 2009). This evidence for withholding EN is weak, and there is no definition of
“safe” doses of vasoactive agents. The purpose of this paper is to review past and current clinical
practices and give further guidance to the practitioner on when to initiate or continue enteral
feeds in the critically ill patient requiring vasoactive agents.
SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
3
Discussion of the Problem
Critically ill patients require several therapies for support during the high stress response
state. Early initiation of nutritional support is important in order to prevent malnutrition and
maintain a healthy immune modulating response to prevent further deterioration and
complications, while also allowing for metabolic compensation during a time of oxygen supply
and demand mismatch (McClave et al., 2009). The rapidly growing population of adults greater
than age 65 increases the likelihood of caring for the elderly population within the critical care
environment. Many times, this population arrives to the ICU in a malnourished state, leading to
increased risk for infection, prolonged healing times, and increased length of stay and increased
mortality (Reid & Allard-Gould, 2004). Along with caring for the growing population of elderly
critically ill patients requiring nutrition therapy, the practitioner must decide when it is safe to
initiate, or continue EN in younger patients with hemodynamic instability requiring
vasopressors, while also preventing further complications related to lack of nutritional support.
Vasoactive agents are frequently required in hemodynamically unstable patients to
maintain sufficient blood flow to vital organs such as the brain and heart, but often times cause
decreased blood flow to the gastrointestinal (GI) tract. Hemodynamic improvement and
adequate fluid resuscitation do not guarantee return to normal GI blood flow, so commonly EN is
avoided until patients no longer require vasopressor support (Allen, 2012). The concern is that
nutrient absorption causes increased oxygen demand and consumption, which could compromise
splanchnic blood flow (Khalid, Doshi, & DiGiovine, 2010). Also, splanchnic and mesenteric
blood flow are effected differently depending on the individual vasopressor agent used (Mancl &
Muzevich, 2013). Effective and safe delivery of EN remains a common concern in patients
requiring vasopressor support due to the increased risk of complications associated with a low
SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
4
flow state including mesenteric ischemia, gastrointestinal hypoperfusion, and decreased
peristalsis which could ultimately lead to non-occlusive bowel ischemia and necrosis (Yang, Wu,
Yu, & Li, 2014). Signs indicating small bowel ischemia and necrosis include abdominal pain
and distention, high nasogastric output, and signs of ileus, however, these are non-specific and
may be interpreted as GI intolerance (Allen, 2012). Individual relative risk for complications
must be evaluated in order to determine the appropriate progression of EN among patients
requiring IV vasopressor support.
Literature Review
A thorough review of the literature revealed a lack of large randomized control studies
evaluating the safety of EN and vasoactive agents in hemodynamically unstable patients. One
retrospective cohort study evaluated EN in mechanically ventilated patients with and without
septic shock (Rai, O’Connor, Lange, Rivett, & Chapman, 2010). This study looked at 43 adult
patients in an ICU with a mean age of 54 years, 33 of which were in shock, with all patients
receiving initiation of EN within one and a half days of admission for a total of seven days. The
data studied included demographics, ICU outcomes, timing of initiation of feeds after ICU
admission, type of feeds, net volume of feeds, total daily aspirate volumes, type and cumulative
dosage of inotropes and sedatives, net calories and protein administered, and presence of
simultaneous administration of PN (Rai et al., 2010). Norepinephrine was the vasopressor most
commonly used, with a mean daily requirement of eight milligrams (5.5 mcg/min), followed by
epinephrine at one milligram per twenty four hours (0.6 mcg/min).
The study revealed that patients received 65% of daily nutritional goals from the enteral
route, and there was no relationship between age, ICU outcome, or presence of pre-existing co-
SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
5
morbid conditions and the success of EN. Initiation of feeding was not affected by the presence
of shock, however, those patients with shock had higher daily gastric aspirate volumes than those
without shock (113mL versus 39mL, P=.02), which was not associated with decreased success of
feeding (Rai et al., 2010). Additionally, patients requiring vasopressor support for a longer
period of time were more likely to have larger volumes of aspirate (P=.09) and decreased daily
total caloric intake (P=.06), suggesting intolerance.
There were several limitations to this study including small sample size and specific
exclusion factors including patients mechanically ventilated for less than three days, patients
with intestinal obstruction, laparotomy, or intra-abdominal pathology, which make the results
difficult to generalize to all critically ill patients who may otherwise benefit EN. There was also
uncertainty in this study in clinically identifying feeding intolerance and delayed gastric
emptying. While this study showed that EN can be considered in hemodynamically unstable
patients requiring vasopressors, it is non-specific regarding EN tolerance with vasoactive agents,
and showed the need for further research.
A larger retrospective study from 2010 investigated the outcomes of critically ill patients
treated with vasopressors and mechanical ventilation in combination with EEN (Khalid, Doshi,
& DiGiovine, 2010). This study included 1174 patients, with a mean age of 65 years, who
required vasopressor agents for blood pressure support as well as more than two days of
mechanical ventilation. Two groups were investigated; those receiving EN within 48 hours of
the start of mechanical ventilation (707 patients), and those who did not (467 patients). All
patients investigated were given norepinephrine, epinephrine, dopamine, or phenylephrine during
the first two days of mechanical ventilation, and were further subdivided into patients given two
or more vasopressor agents, and patients treated with vasopressors for more than two days after
SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
6
the start of mechanical ventilation. Race, sex, age, admitting diagnosis, medications received,
Simplified Acute Physiologic Score (SAPS II), Mortality Prediction Model at time zero (MPM0), and Acute Physiologic and Chronic Health Evaluation (APACHE) II score (Khalid et al.,
2010) were the study variables, with older patients being most likely included in the EEN group.
The primary outcome data were hospital and ICU mortality, and secondary outcome data
included ICU length of stay, ventilator-free days, vasopressor-free days, and occurrence of
ventilator-associated pneumonia (VAP). The analysis of the data revealed a decrease in ICU
mortality (22.5% versus 28.3%, P=.03) and hospital mortality (34% versus 44%, P<.001) and
overall survival in patients receiving EEN despite the use of vasopressors, especially in those
patients requiring multiple vasopressors, compared to those patients with late feeding (P=.01)
(Khalid et al., 2010). There was also no evidence of harm found in patients with EEN and the
use of vasoactive agents.
Limitations to the study include an intent-to-treat analysis and lack of randomization, as
well as not taking into account the total caloric intake, rate of advancement in tube feed, and
whether disruption of feeding occurred. A clear definition of exact vasopressors used, along
with mean dosage was never identified. Also, certain patient populations such as GI obstruction
or bleed, intestinal ileus, pancreatitis, peritonitis, and gastroparesis were excluded due to the
contraindication to EN, which make the results difficult to apply to all patients in the critical care
environment. This study showed there may be more benefit than harm of EEN in
hemodynamically unstable patients requiring vasoactive agents, however, a large, prospective
randomized trial was recommended for further evaluation of the problem.
SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
7
Mancl and Muzevich (2013) conducted a retrospective medical record review to evaluate
the safety and tolerability of EN in adult critically ill patients receiving IV vasopressors. Two
hundred fifty-nine patients, with a mean age of 57 years, received 346 episodes of concomitant
IV vasopressor therapy and tube feeding for greater than one hour. Several study variables were
recorded, but of significance were age, type of shock, duration of EN and vasopressor overlap,
median mean arterial pressure (MAP), initial and goal rate of EN products, presence of gastric
residuals greater than 300mL, and specific vasopressors used, with initial, mean, and maximum
doses.
The primary outcome of this study was EN tolerance, defined as absence of positive
findings on abdominal radiography or computed tomography (CT), increased gastric residuals of
greater than 300mL, emesis, or presence of bowel ischemia or perforation. Specific dosages of
vasopressors, and rates of mortality and adverse events were secondary outcomes. Tolerability
of concomitant IV vasopressor therapy and EN was 74.9%. Adverse events related to EN
intolerance included 36.6% positive abdominal radiography studies, 0.9% positive CT studies,
14.5% occurrence of gastric residuals greater than 300mL, 9% of patients with emesis, and a
0.9% presence of bowel ischemia or perforation (Mancl & Muzevich, 2013). Patients receiving
lower maximum doses of norepinephrine (12.5 mcg/min) had better tolerance than those with
higher maximum doses (19.4 mcg/min) (P=.0009). Patients who never received vasopressin
(58.9% versus 77.9%, P=.0027) or dopamine (63.8% versus 77.6%, P=.018) also had increased
EN tolerance, demonstrating that tolerability was less likely in patients receiving either of these
vasopressors. EN tolerance was more likely in patients who received phenylephrine compared to
those who did not receive phenylephrine (100% versus 73%, P=.0023) (Mancl & Muzevich,
2013).
SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
8
Several notable limitations are found in this study. The retrospective study design could
have lead to selection bias in the data obtained. Timing of EN initiation was also not addressed.
Meeting goal nutrition was not included in the definition of tolerability, therefore it is unknown
how quickly each patient reached goal nutrition, and for how long it was obtained. Early
detection of bowel ischemia can be seen with trending serum lactate, however, this study did not
associate increasing lactate levels with decreased EN intolerance (Mancl & Muzevich, 2013).
Also, included in the definition of EN tolerability was the absence of positive abdominal
radiographic images or CT, however, patients who underwent such testing may have had other
signs of intolerance such as abdominal distention or pain. This study provided evidence that EN
can be tolerated in patients receiving IV vasopressor support, depending on the medication and
dosages used. Phenylephrine seems to provide the safest option for delivery of EN with the use
of vasoactive agents, however, its use is not recommended in the sepsis guidelines, and
norepinephrine and vasopressin should be used as first line agents in hemodynamic instability
(Dellinger et al., 2013). Further research is warranted regarding whether patients requiring
hemodynamic support would have improved outcomes from EN.
Summary
The debate remains on the safety of EN and vasoactive agents in hemodynamically
unstable patients. Each study addresses concerns of EN and vasoactive agents, and gives
guidance to the clinician for progressing with nutritional therapy in hemodynamically unstable
critically ill patients. While the A.S.P.E.N. (2009) guidelines suggest withholding EN in patients
requiring high dose catecholamine agents until the patient is stable, research is lacking on the
definition EN tolerance to specific vasoactive agents and dosages, when EN should be initiated
in patients requiring vasoactive agents, and whether patients with hemodynamic instability
SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
9
would have improved outcomes with EN therapy. A common theme among the studies reviewed
is that in patients receiving IV vasopressor support, administration of EN may be considered
with careful monitoring. Individual relative risk for complications should be taken into account
regarding patient age, pre-existing nutritional status, current problem, physical exam, laboratory
data, and overall clinical picture.
Although mortality associated with non-obstructive bowel ischemia and necrosis is high
(80%), the relationship between this complication and EN has not been clearly proven in the data
(Yang et al., 2014). Risk versus benefit ratio must be evaluated for individual patients during
hemodynamic instability. Low-volume “trophic” feeding may be a safer alternative for
nutritional therapy in patients requiring vasoactive agents during hemodynamic instability,
however, close monitoring of GI intolerance and ischemic injury is important to prevent
complications.
Role of the AG-ACNP
The role of the AG-ACNP, as with any provider in critical care, is to effectively manage
the hemodynamically unstable patient aiming to achieve optimal outcomes, including that in the
delivery of safe and effective nutritional therapy. While guidelines recommend cessation of EN
during vasopressor requirement, safe delivery of enteral nutrition may be achieved in certain
patient populations, and may be required in certain populations like the elderly or
undernourished in order to achieve the best outcomes. The AG-ACNP can promote the
importance of EEN, and assist in monitoring for adverse effects related to decreased tolerance
and complications in those patients still requiring vasopressor support. The AG-ACNP can also
SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
10
assist in developing protocol-directed enteral feeding in both hemodynamically stable and
unstable patients to increase the compliance and delivery of effective nutritional therapy.
Conclusion
Due to the lack of evidence on the problem, clinicians should proceed with caution in
initiating or continuing EN in patients receiving vasoactive agents during hemodynamic
instability. The purpose of this paper was not obtained, and more research must be done to reach
a consensus for proceeding. Nutritional therapy should be based on a case-by-case occurrence,
with close evaluation of patient tolerance through frequent abdominal exams, gastric residual
checks, laboratory studies, and abdominal x-rays.
SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
11
References
Allen, J. (2012). Vasoactive substances and their effects on nutrition in the critically ill patient.
Nutrition in Clinical Practice, 27(3), 335-339. doi: 10.1177/0884533612443989
Dellinger, P., Levy, M., Rhodes, A., Annane, D., Gerlach, H., Opal, S., …& Moreno, R. (2013).
Surviving sepsis campaign: guidelines for management of severe sepsis and septic
shock: 2012. Critical Care Medicine, 41(2), 580-637. doi:
10.1097/CCM.0b013e31827e83af
Khalid, I., Doshi, P., & DiGiovine, B. (2010). Early enteral nutrition and outcomes of critically
ill patients treated with vasopressors and mechanical ventilation. American Journal of
Critical Care, 19(3), 261-268. doi: 10.4037/ajcc2010197
Mancle, E., & Muzevich, K. (2013). Tolerability and safety of enteral nutrition in critically ill
patients receiving intravenous pressor therapy. Journal of Parenteral and Enteral
Nutrition, 37(5), 641-651. doi: 10.1177/0148607112470460
McClave, S., Martindale, R., Vanek, V., McCarthy, M., Roberts, P., Taylor, B., …& Cresci, G.
(2009). Guidelines for the provision and assessment of nutrition support therapy in the
adult critically ill patient: Society of Critical Care Medicine (SCCM) and American
Society for Parenteral and Enteral Nutrition (A.S.P.E. N.). Journal of Parenteral and
Enteral Nutrition, 33(3), 277-316. doi: 10.1177/0148607109335234
Rai, S., O’Connor, S., Lange, K., Rivett, J., & Chapman, M. (2010). Enteral nutrition for
patients in septic shock: a retrospective cohort study. Critical Care and Resuscitation,
12(3), 177-181.
SAFETY OF ENTERAL NUTRITION AND VASOACTIVE AGENTS
Reid, M., & Allard-Gould, P. (2004). Malnutrition in the critically ill elderly patient. Critical
Care Nursing Clinics of North America, 16, 531-536. doi:10.1016/j.ccell.2004.06.007
Turza, K., Krenitsky, J., & Sawyer, R. (2009). Enteral feeding and vasoactive agents:
suggested guidelines for clinicians. Practical Gastroenterology, 11-22.
Yang, S., Wu, X., Yu, W., & Li, J. (2014). Early enteral nutrition in critically ill patients with
hemodynamic instability: an evidence-based review and practical advice. Nutrition in
Clinical Practice, 29(1), 90-96. doi: 10.1177/0884533613516167
12