TPN 시작 시기(1) ASPEN : timing of initiating TPN, partial PN(supplement PN) 도입 여부

2016 ASPEN

 

☝ When to Use PN

 

1) When should PN be initiated in the adult critically ill patient at low nutrition risk?

We suggest that, in the patient at low nutrition risk (eg, NRS 2002 ≤3 or NUTRIC score ≤5), exclusive PN be withheld over the first 7 days following ICU admission if the patient cannot maintain volitional intake and if early EN is not feasible.

2) When should PN begin in the critically ill patient at high nutrition risk?

Based on expert consensus, in the patient determined to be at high nutrition risk (eg, NRS 2002 ≥5 or NUTRIC score ≥5) or severely malnourished, when EN is not feasible, we suggest initiating exclusive PN as soon as possible following ICU admission.

 

Low nutrition risk	NRS 2002 ≤3 or NUTRIC score ≤5	Exclusive PN be withheld over the first 7 days following ICU admission if the patient cannot maintain volitional intake and if early EN is not feasible.
High nutrition risk or severely malnourished	NRS 2002 ≥5 or NUTRIC score ≥5	When EN is not feasible, we suggest initiating exclusive PN as soon as possible following ICU admission.

 

ICU 환경에서 PN 사용에 대한 위험/효익비는 EN 사용에 대한 위험/효익비보다 훨씬 좁다. 이전에 영양 상태가 양호한 환자의 경우, PN을 사용하면 ICU의 입원 첫 주 동안 별 효익이 없다. PN 의존 환자(eg. short bowel)의 경우, 균혈증(bacteremia)를 제외하면 ICU 입원하자마자 PN 시작을 권고한다.

Two trials have addressed the timing of initiation of exclusive PN therapy.

1. EPaNiC study:　patients for whom use of PN was started on ICU day 3 had worse infectious morbidity and were less likely to be discharged alive than those patients for whom PN was started instead on day 8.

2. EN 금기인 중증 환자가 포함된 대형 RCT에서 입원 후 24시간 이내 PN을 사용하는 것은 영양 치료가 제공되지 않은 STD(Standard therapy refers to provision of intravenous (IV) fluids, no EN or PN, and advancement to oral diet as tolerated.)에 비해 최소한의 효익을 보였다.

 

With increased duration of severe illness, the risk for deterioration of nutrition status increases, and priorities between STD and PN become reversed. (중증 질환 기간이 길어질수록 영양 상태 악화 위험이 노파지고 STD와 PN의 우선 순위가 뒤바뀐다.)

Little data exist to direct the timing of initiating PN in the ICU.

Although the literature cited recommends withholding PN for 10–14 days, the Guidelines Committee expressed concern that continuing to provide STD beyond 7 days would lead to deterioration of nutrition status and an adverse effect on clinical outcome.

STD in malnourished ICU patients was associated with significantly higher risk for mortality (RR = 3.0; 95% CI, 1.09–8.56; P < .05) and a trend toward higher rate of infection (RR = 1.17; 95% CI, 0.88–1.56; P value not provided) compared with use of PN. (영양 고위험 환자군에서는 PN군보다 STD군에서 사망률이나 감염 위험이 더 높았다. 이런 군에서 PN 시작을 연기하지 않는 것이 좋다.

 

3) What is the optimal timing for initiating supplemental PN when EN does not meet energy or protein goals in the patient at low or high nutrition risk?

We recommend that, in patients at either low or high nutrition risk, use of supplemental PN be considered after 7–10 days if unable to meet >60% of energy and protein requirements by the enteral route alone. Initiating supplemental PN prior to this 7- to 10-day period in critically ill patients on some EN does not improve outcomes and may be detrimental to the patient.

이미 일정량의 EN을 받은 환자의 경우, 처음 7-10일 동안 partial PN(supplemental PN)을 사용하면 에너지와 단백질 제공량을 증가시킬 수 있다. 하지만 partial PN의 경우 비싸고 ICU 재원 초기에 제공되었을 때 효익이 적다.

 

1. 대규모의 다기관 observational study에서 초기(48시간 이내) partial PN은 이점이 없음을 밝혔다.

early enteral nutrition alone, early enteral nutrition + early parenteral nutrition, and early enteral nutrition + late parenteral nutrition (after 48 hrs of admission) 2562 (87.7%) in the early enteral nutrition group, 188 (6.4%) in the early parenteral nutrition group, and 170 (5.8%) in the late parenteral nutrition group.

Adequacy of calories from total nutrition.

Kaplan-Meier curves of proportion of patients discharged from hospital alive.

Clinical outcomes

중증 환자에게 조기 또는 후기 partial PN을 사용하면 열량과 단백질의 공급이 개선되지만 입원 기간이나 사망률의 임상 결과는 개선되지 않는다. 이에 대한 권고사항을 확고히 하기 위한 추가적인 무작위 시험이 필요하다.

 

2. 2개의 센터에서 시행된 RCT에서 EN에 의해 목표 에너지와 단백질의 60%를 획득한 환자에 대해 입원 후 3일 때 추가된 partial PN은 저칼로리(hypocaloric) EN을 계속 받는 대조군과 비교할 때 결과 편익이 거의 없었다.

 

3. 또 다른 다중 센터에서 시행된 RCT에서 저칼로리 EN을 받는 환자 중 ICU 입원 8일이 되는 시점에 개시된 partial PN군과 3일 되는 시점에서 개시된 partial PN군을 비교하였을 때 being discharged alive from the ICU의 가능성이 더 높았다. (HR = 1.06; 95% CI, 1.00–1.13; P = .04)

 

☝☝🙄🙄각 연구간 특징: partial PN 단독으로 시작한 실험군은 없었다!

 

결론: The optimal time to initiate supplemental PN in a patient who continues to receive hypocaloric EN is not clear. At some point after the first week of hospitalization, if the provision of EN is insufficient to meet requirements, then the addition of supplemental PN should be considered, with the decision made on a case-by-case basis.

 

 

☝ When Indicated, Maximize Efficacy of PN

 

1) When PN is needed in the adult critically ill patient, what strategies can be adopted to improve efficacy?

Based on expert consensus, we suggest the use of protocols and nutrition support teams to help incorporate strategies to maximize efficacy and reduce associated risk of PN.

Refeeding syndrome risk factor: alcoholism, weight loss, low body mass index [BMI], prolonged periods NPO

EN을 시작할 때도 refeeding syndrome 위험이 있지만 특히 PN을 시작할 때 더 위험하다. 위험군에서는 목표 열량 달성을 위해 3-4일이 걸리는 등의 공급을 더 천천히 해야 한다.

2) In the appropriate candidate for PN (high risk or severely malnourished), should the dose be adjusted over the first week of hospitalization in the ICU?

We suggest that hypocaloric PN dosing (≤20 kcal/kg/d or 80% of estimated energy needs) with adequate protein (≥1.2 g protein/kg/d) be considered in appropriate patients (high risk or severely malnourished) requiring PN, initially over the first week of hospitalization in the ICU.

ICU에서 PN을 필요로 하는 환자에게 저칼로리(≤20 kcal/kg/d or no more than 80% of estimated energy needs) & 적절한 단백질 공급(≥1.2 g protein/kg/d) 전략이 혜택을 받을 수 있다. 이 전략은 고혈당 및 인슐린 저항성의 가능성을 감소시킴으로써 중증 질환의 초기 단계에서 PN의 효능을 최적화할 수 있다.

환자가 안정화되었을 때 PN으로 공급한 에너지가 estimated energy requirements을 100% 충족할 수 있도록 해주는 것이 좋다.

 

3) Should soy-based IV fat emulsions (IVFEs) be provided in the first week of ICU stay? Is there an advantage to using alternative IVFEs (ie, medium-chain triglycerides [MCTs], olive oil [OO], FO, mixture of oils) over traditional soybean oil (SO)–based lipid emulsions in critically ill adult patients?

We suggest withholding or limiting SO-based IVFE during the first week following initiation of PN in the critically ill patient to a maximum of 100 g/wk (often divided into 2 doses/wk) if there is concern for essential fatty acid deficiency.

Alternative IVFEs may provide outcome benefit over soy-based IVFEs; however, we cannot make a recommendation at this time due to lack of availability of these products in the United States. When these alternative IVFEs (SMOF [soybean oil, MCT, olive oil, and fish oil emulsion], MCT, OO, and FO) become available in the United States, based on expert opinion, we suggest that their use be considered in the critically ill patient who is an appropriate candidate for PN.

2016년도 ASPEN 가이드라인이 나올 당시 미국에서는 soy-based 18-carbon omega-6 fatty acid가 함유된 lipid 제형만 존재했다.

입원 후 처음 10일 동안 IVFE가 없는 PN을 제공한 외상 환자는 감염성 질병이 유의미하게 감소하였다(예: P = 0.05, 카테터 관련 패혈증, P = 0.04)

하지만 IVFE는 좋은 에너지 공급 수단이므로 IVFE가 없는 PN 제형을 공급하였을 때 칼로리 요구량보다 적은 양을 공급받을 수 있다. (21 kcal/kg/d vs 28 kcal/kg/d)

반대로 A similar study comparing a hypocaloric IVFE-free regimen (1000 total kcal/d and 70 g of protein/d) versus an SO-based IVFE standard admixture (25 kcal/kg/d and 1.5 g of protein/d) found no significant differences in infectious complications, hospital LOS, or mortality. This finding was confirmed by a large observational study that reviewed outcomes in patients who received PN for ≥5 days in multi-international ICUs. IVFE-free PN vs. SO-based IVFE에서 임사적으로 유의한 결과 차이를 보이지 않았다.

빠른 지질 주입 속도는 reticuloendothelial system가 망가지고 고중성지방혈증으로 이어질 수 있다.

SO가 아닌 다른 IVFE는 PN의 위험/효익을 개선할 수 있다. 806명의 환자가 포함된 12개의 RCI의 systematic review에서는 편익 측면에서 유의미한 차이를 보이지 않았다.

391명의 환자가 포함된 8개 RCT의 메타 분석은 오메가-3의 효과를 비교했다. SO 기반 또는 SO+MCT 기반 IVFE 결과를 통해 FO 기반 IVFE vs 다른 지방 공급원의 사용에 비해 병원 LOS가 거의 10일(WMD = –9.49; 95% CI, –16.5 ~ –2.5; P =.008) 감소했지만 그룹 간에 차이가 발견되지 않았다.

A subgroup analysis within the Manzanares et al meta-analysis found a significant reduction in the duration of mechanical ventilation (WMD = −6.47; 95% CI, −11.41 to −1.53; P = .01) in favor of the OO-based IVFE, although there were no differences for mortality or ICU LOS.

이러한 문헌의 결과에도 불구하고 미국에서는 이 당시 SO based IVFE 이외의 지질 제형이 없기 때문에 이에 대한 권고를 하기 어렵다.

 

 

4) Is there an advantage to using standardized commercially available PN (premixed PN) versus compounded PN admixtures?

Based on expert consensus, use of standardized commercially available PN versus compounded PN admixtures in the ICU patient has no advantage in terms of clinical outcomes.

 

5) In transition feeding, as an increasing volume of EN is tolerated by a patient already receiving PN, at what point should the PN be terminated?

Based on expert consensus, we suggest that, as tolerance to EN improves, the amount of PN energy should be reduced and finally discontinued when the patient is receiving >60% of target energy requirements from 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) Kutsogiannis, Jim, et al. "Early use of supplemental parenteral nutrition in critically ill patients: results of an international multicenter observational study." Critical care medicine 39.12 (2011): 2691-2699.