영양소의 적절한 흡수 & 소화를 위해서는 위장관으로 적절한 혈액 흐름이 필요하다.
중환자에서 조기 경장 영양(enteral feeding; EN) 섭취에 대한 권고에도 불구하고 이러한 약제를 투여 받는 환자에서 안전하고 효과적인 EN의 최적의 시기에 대한 논란이 여전히 존재한다.
혈역학적 불안정을 위해 vasoactive-inotrope agent가 요구되는 환자에서 EN의 시작을 연기하는 것은 소장의 괴사 예방을 위함이다.
NUTRITEA-2 study
Critical illness* 상태 발병 24시간 이내 vasoactive agent 투여 받은 성인 중환자 중 EN or PN을 시작 (* : endotracheal intubation )
결론: 급성기에 early full feeding EN은 bowel ischemia 등의 위장관 합병증을 증가
These findings provide scientific support for recommendations to postpone full enteral nutrition until haemodynamic stability is restored and to prefer parenteral nutrition or no nutrition in patients at the worst end of the severity spectrum.
In conclusion, our trial shows that the enteral route is not clinically superior over the parenteral route for early nutritional support with a normocaloric target in critically ill patients treated with mechanical ventilation and vasopressor support for shock. Our data indicate an increased risk of gastrointestinal complications with early isocaloric enteral nutrition compared to parenteral nutrition in these patients.
2016 ASPEN
Q) Is EN safe during periods of hemodynamic instability in adult critically ill patients?
A) Based on expert consensus, we suggest that in the setting of hemodynamic compromise or instability, EN should be withheld until the patient is fully resuscitated and/or stable. Initiation/reinitiation of EN may be considered with caution in patients undergoing withdrawal of vasopressor support.
While EN may be provided with caution to patients on chronic, stable low doses of vasopressors, EN should be withheld in patients who are hypotensive (mean arterial blood pressure <50 mm Hg), in patients for whom catecholamine agents (eg, norepinephrine, phenylephrine, epinephrine, dopamine) are being initiated, or in patients for whom escalating doses are required to maintain hemodynamic stability.
For patients on vasopressor therapy receiving EN, any signs of intolerance (abdominal distention, increasing nasogastric [NG] tube output or GRVs, decreased passage of stool and flatus, hypoactive bowel sounds, increasing metabolic acidosis and/or base deficit) should be closely scrutinized as possible early signs of gut ischemia, and EN should be held until symptoms and interventions stabilize.
2019 ESPEN
EN should be delayed
if shock is uncontrolled and hemodynamic and tissue perfusion goals are not reached, whereas low dose EN can be started as soon as shock is controlled with fluids and vasopressors/inotropes, while remaining vigilant for signs of bowel ischemia.
<Vasoactive Substances Used in the Intensive Care Unit>
| 성분명 /기전 /일반적인 용량 |
임상적 사용 | Gastrointestinal effect |
| Dobutamine /β-1 agonist /2.5–20 mcg/kg/min Max: 40 mcg/kg/min |
Heart failure | Increases GI mucosal blood flow, increases gastric intramucosal pH (pHi) |
| Dopamine /Dopa, α, β-1 agonist / 5–20 mcg/kg/min Max: 50 mcg/kg/min |
Septic shock bradycardia |
Decreases pHi, increases oxygen delivery (septic shock), precapillary vasoconstriction with diversion of blood away from GI mucosa |
| Epinephrine /α, β-1, β-2 agonist /0.05–0.5 mcg/kg/min Max: 1 mcg/kg/min |
Shock cardiac arrest anaphylaxis heart block bradycardia |
Decreases splanchnic blood flow |
| Norepinephrine /α, β-1 agonist /0.05–1.5 mcg/kg/min Max: 3 mcg/kg/min |
Septic shock | Increases gastric pHi, increases splanchnic blood flow (septic shock), decreases mucosal blood flow (hypovolemia) |
| Phenylephrine /α agonist /0.4–9.1 mcg/kg/min |
Septic shock hypotension |
- |
| Vasopressin /Antidiuretic hormone analogue /0.01–0.04 U/min |
Hypotension septic shock to decrease pressor requirements diabetes insipidus GI bleed esophageal varices |
Increases intestinal vasoconstriction (may cause gastric mucosal acidosis), enhances pressor response |
하지만 이러한 우려에도 불구하고 조기 EN에 대한 이점을 시사하는 연구가 많이 발표되고 있다. 해당 연구들은 후향적 연구라는 한계를 가지고 있지만 NUTRITEA-2 연구의 방법(full feeding) 등을 고려하여 높은 VIS(vasoactive inotropic score)의 가진 환자에서 EN 시 hypocaloric feeding/gradually increasement method/각 센터에 맞는 맞춤 protocol 설정을 해볼 수 있다. (개인 의견)
Journal of parenteral and enteral nutrition 37.5 (2013): 641-651.
충분한 fluid 소생이 이루어지고 혈역학적 안정적인 중환자에서 24-48시간 이내 EN의 시작은 권장된다 하지만 혈역학적 안정에 대해서는 잘 정의되지 않는다. 각 가이드라인에서 말하는 “low-dose” vs "high-dose" catecholamine의 무엇인가?
Methods
A retrospective medical record review was conducted in an urban academic medical center and included adult ICU patients from 2011 who received concomitant EN and IV vasopressor therapy for ≥1 hour.
Vasopressor data collected included agents used and the initial, mean, and maximum dosages during overlap episode. Vasopressor dosages were converted to norepinephrine equivalents using the following formula: norepinephrine equivalents = [norepinephrine (mcg/min)] + [dopamine (mcg/kg/min) ÷ 2] + [epinephrine (mcg/min)] + [phenylephrine (mcg/min) ÷ 10] + [vasopressin (units/h) × 8.33].
EN-IV vasopressor overlap?
(1) tube feeding의 시작과 끝에 IV vasopressor 주입의 기록이 있을 때
(2) IV vasopressor의 시작과 끝에 tube feeding의 기록이 있을 때
EN과 IV vasopressor 치료의 병용이 1건(episode)이라도 있는 환자군을 대상으로 하였음
Results
Total of 259 patients were included with a total of 346 overlap episodes. Of the 346 overlap episodes, there were 259 cases (median 74.9%) of EN tolerance.두 군에서 MAP은 유사하였다. (median 74.8 vs 74.7 mm Hg, P = .72)
EN 내약성이 있는 군에서 overlap 기간의 중앙값이 더 짧았다. (26 vs 65 hours, P = .0002)
EN 내약성군에서 평균 칼로리 투여량이 더 많았다. (13.6 vs 10.9 kcal/kg/d, P = .0034).
EN 내약성군에서 젖산 수치의 증가가 덜 발생하였다. (25.5% vs 46.0%, P = .0003) 하지만 this association did not maintain statistical significance in multivariate logistic regression. (Table 2)
EN 내약성군에서 위장관계 약제(promotility agent)를 덜 사용하였다. (15.0% vs 44.0%, P < .0001).
부작용
A dose-response relationship was observed between maximum norepinephrine equivalent and likelihood of tolerating EN.
Tolerability was stratified by individual IV vasopressor as well as cumulative IV vasopressor dose.
Patients who tolerated EN received a lower maximum norepinephrine equivalent dose compared with those who did not tolerate EN (12.5 vs 19.4 mcg/min, P = .0009).
Tolerability differed based on the vasopressor administered. (어떤 vasopressor인가에 따라서 내약성이 달라짐)
Discussions
일차 연구 목표는 IV vasopressor 치료를 받는 중환자 환자에서 EN의 허용 가능성을 평가하는 것이었다. 전반적으로, 우리는 중환자 환자에게서 이전에 보고된 것보다 더 높은 EN 허용 가능성(EN tolerability rate)을 발견했다.
이는 head elevation(침상 높임)이나 위 잔류량(gastric residual volume)의 임계치를 상이하게 평가하였기 때문일 수도 있다. 또한 목표 칼로리를 충족시켜야 한다는 조건을 tolerability의 정의에 포함시키지 않았다.(즉 hypocaloric EN까지 용인하였다.) type of EN product의 차이로 인한 설사(associated with high-osmolarity EN formulas)를 평가하지 않았다. CT 이미지 등을 EN tolerability 평가에 포함시켰는데 이는 주관적 요소이다.
본 연구에서는 "12.5 mcg/min of norepinephrine or more"를 고선량 카테콜아민으로 정의할 수 있는 근거를 제공한다.
IV vasopressor 받는 환자에게 EN을 투여하였을 때 허혈성 위장관 부작용의 발생률은 낮기 때문에(0.9%) 상당히 안전한 것으로 생각된다. IV vasopressor가 허혈 부작용을 유발할 수는 있지만 전체적인 발병률은 EN을 받는 중환자에서 자발적 천공에 대한 문헌적 보고(in the literature for spontaneous perforation in critically ill patients receiving EN) 수치와 비슷하다.
IV vasopressor의 종류에 따라서도 EN tolerance에 미치는 영향이 다를 수 있다. VIS 계산식이 있지만 이는 위장관 혈류를 고려한 계산식이 아니다. low VIS 점수가 나오더라도 vasopressin, dopamine을 사용 시 더 주의할 필요가 있다.
Conclusion
Based on our findings, EN is relatively well tolerated in patients receiving IV vasopressor support equivalent to 12.5 mcg/min of norepinephrine or less. Tolerability was less likely in patients receiving higher doses of IV vasopressors and in those receiving dopamine or vasopressin. These patients should be monitored more closely for signs of intolerance. In summary, critically ill patients receiving IV vasopressor support generally tolerate EN.
reference:
1) McClave, Stephen A., et al. "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 (ASPEN)." JPEN. Journal of parenteral and enteral nutrition 40.2 (2016): 159-211.
2) Singer, Pierre, et al. "ESPEN guideline on clinical nutrition in the intensive care unit." Clinical nutrition 38.1 (2019): 48-79.
3) Mancl, Erin E., and Katie M. Muzevich. "Tolerability and safety of enteral nutrition in critically ill patients receiving intravenous vasopressor therapy." Journal of parenteral and enteral nutrition 37.5 (2013): 641-651.
4) Allen, John M. "Vasoactive substances and their effects on nutrition in the critically ill patient." Nutrition in Clinical Practice 27.3 (2012): 335-339.
댓글