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KIỂM SOÁT NĂNG LƯỢNG ĐẠM Ở BN NHIỄM KHUẨN HUYẾT

TS.BS. BÙI THỊ HẠNH DUYÊN

TRƯỞNG KHOA HỒI SỨC TÍCH CỰC-BV ĐHYD TPHCM

PHÓ CHỦ TỊCH HỘI HEN-MIỄN DỊCH-DỊ ỨNG LÂM SÀNG TP.HCM

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NỘI DUNG

Thay đổi chuyển hóa ở BN NKH

Nhu cầu đạm ở BN NKH

Ca lâm sàng

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Suy mòn cơ ở BN hồi sức

Tình trạng dị hóa nghiêm trọng liên quan tình trạng tăng chuyển hóa

Tiêu thụ năng lượng và ly giải protein
Kháng insulin
Cân bằng nitơ âm
Bất động

Fazzini B, et al. The rate and assessment of muscle wasting during critical illness: a systematic review and meta-analysis. Crit Care. 2023 Jan 3;27(1):2. doi: 10.1186/s13054-022-04253-0

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Yếu cơ mắc phải trong BN NKH trong ICU

NC hồi cứu trên 164 BNđược chẩn đoán NKH MODS, có thở máy, nhập ICU tại BV ĐH Y Côn Minh (TQ)
Tỷ lệ mắc yếu cơ mắc phải là 25,6% (42/164).
Albumin thấp, thời gian thở máy kéo dài, nồng độ myoglobin cao và thời điểm bắt đầu nuôi BN NKH kèm MODS.�

Yu X, et al . DOI: 10.3760/cma.j.issn.2095-4352.2018.04.014

Yu X, Wan X, Wan L, Huang Q. [Analysis of high risk factors of intensive care unit-acquired weakness in patients with sepsis]. Zhonghua wei Zhong Bing ji jiu yi xue. 2018 Apr;30(4):355-359. DOI: 10.3760/cma.j.issn.2095-4352.2018.04.014. PMID: 29663999

Yu X, et al . DOI: 10.3760/cma.j.issn.2095-4352.2018.04.014. PMID: 29663999

Abstract

Objective

To investigate high risk factors of intensive care unit-acquired weakness (ICUAW) in patients with sepsis.Methods

A retrospective study was conducted. 164 patients with mechanical ventilation (MV) who were diagnosed sepsis and multiple organ dysfunction syndrome (MODS), admitted to intensive care unit (ICU) of the Second Affiliated Hospital of Kunming Medical University from January 1st, 2015 to September 30th, 2017 were enrolled. The general situation, the basic diseases (hypertension, diabetes), body mass index (BMI), protopathy diseases, the level of albumin before ICU admission, the MV time, whether to use glucocorticoid and continuous renal replacement therapy (CRRT) or not, nutrition supply (nutritional way, nutrition initiation time, amino acid/protein supply, nutritional status on ICU 3 days and 7 days), myoglobin, the length of ICU stay, the length of hospital stay, and acute physiology and chronic health evaluation II (APACHE II) score were collected. The high risk factors of ICUAW in patients with sepsis complicated with MODS were analyzed further using multi-factor Logistic regression analysis. Multiple linear regression analysis was used to analyze the myoglobin related factors in sepsis patients.Results

The ICUAW incidence was 25.6% (42/164). The risk factors with differences in univariate analysis were included in the multivariate Logistic regression analysis, and it was shown that the level of albumin before ICU [odds ratio (OR) = 0.232, 95% confidence interval (95%CI) = 0.061-0.885, P = 0.032], the MV time (OR = 0.380,95%CI = 0.154-0.935, P = 0.035), nutrition initiation time (OR = 2.642, 95%CI = 1.100-6.346, P = 0.030), myoglobin (OR = 4.129, 95%CI = 1.681-10.142, P = 0.002) were the independent risk factors for ICUAW in sepsis patients with MODS. The linear regression showed that the level of myoglobin was positively correlated with APACHE II score (β= 38.297, P = 0.000), negatively correlated with the length of hospital stay (β= -7.071, P = 0.048), and it had nothing to do with the MV time and the length of ICU stay.Conclusions

Evaluation of muscle function should be a routine part of ICU examination. The levels of albumin, MV time, hemoglobin and nutritional start-up time were independent risk factors for ICUAW in sepsis patients with MODS. Myoglobin levels can be used as an indicator of severity.

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Tăng chuyển hóa ở BN NKH

Pravda J. Metabolic theory of septic shock. World J Crit Care Med. 2014;3(2):45-54. Published 2014 May 4. doi:10.5492/wjccm.v3.i2.45

The above evidence supports a pathogenesis of septic shock which is initiated by the systemic depletion of glutathione as the crucial event responsible for the accumulation of H₂O₂ in tissues. Subsequent diffusion of H₂O₂ into the blood stream leads to systemic elevation of this highly toxic oxidizing agent resulting in the microvascular dysfunction and organ failure observed in septic shock (Figure 1).

Septic shock begins with a systemic inflammatory reaction to an infection. A contemporaneous increase in metabolism is initiated, which can deplete reserves of critical nutrients such as glutathione. Glutathione is crucial for the neutralization of H₂O₂, a toxic, membrane-permeable oxidizing agent generated as a by-product of cellular metabolism. Depletion of cellular glutathione results in elevation of H₂O₂ which can diffuse out of organ parenchymal cells and into capillary endothelium before reaching the bloodstream. Once in the systemic circulation, excess H₂O₂ is distributed throughout the body resulting in systemic oxidative damage to plasma components, organs and blood vessels. The net result is H₂O₂ induced coagulopathy, immunocyte apoptosis and microvascular dysfunction leading to disseminated intravascular coagulation, immunosuppression, organ failure and septic shock respectively. H₂O₂ inhibits GPx and catalase, which are critical anti-oxidant enzymes required for H₂O₂ neutralization. This prevents restoration of normal plasma and tissue redox balance while exacerbating oxidative tissue damage. H₂O₂ can also activate nuclear factor-κB (NF-κB) contributing to the inappropriate activation of this master pro-inflammatory transcription factor observed in septic shock. The pathologic activation of NF-kB contributes to elevated tumor necrosis factor-alpha levels, another potent generator of intracellular H₂O₂. GPx: Glutathione peroxidase.

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Thay đổi chuyển hóa trong BN NKH

Gabrielli M, et al, Nutrients. 2024;16(23):3985. Published 2024 Nov 21. doi:10.3390/nu16233985

Gabrielli M, Zaccaria R, Impagnatiello M, Zileri Dal Verme L, Gasbarrini A. Nutritional Strategies for the Treatment and Prevention of Sepsis Outside the Intensive Care Unit. Nutrients. 2024;16(23):3985. Published 2024 Nov 21. doi:10.3390/nu16233985

Gabrielli M, et al, Nutrients. 2024;16(23):3985. Published 2024 Nov 21. doi:10.3390/nu16233985

Figure 1. Schematic representation of the complex metabolic alterations observed in the acute

phase of sepsis. Glucose becomes the primary substrate, as glycolysis has the advantage of not

requiring oxygen, although energy production is significantly lower than in the Krebs cycle. Hepatic

ketogenesis is suppressed by increased insulin levels. This allows peripheral tissues to utilize glucose

as a primary energy source. Hepatic glycogenolysis provides glucose for a short time. This is followed

by intensive endogenous glucose production (gluconeogenesis) in the liver from lactate, amino acids

derived from increased protein catabolism, and glycerol derived from increased lipolysis.

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Thay đổi chuyển hóa trong BN NKH

Thay đổi sinh lý trong nhiễm trùng huyết	Tác động chuyển hóa
Tân tạo glucose, đường phân	Tăng đường huyết
Dị hóa protein	Thay đổi acid amin tuần hoàn
Ly giải mỡ (lipolysis)	Tăng triglycerid, lipoprotein
Vi chất dinh dưỡng	Stress oxy hóa
Hoạt hóa thần kinh nội tiết	Catecholamine, hormone đối kháng điều hòa
Cortisol	Tăng đường huyết
Giải phóng catecholamine	Tân tạo glucose, đường phân
Giải phóng cytokine	Tăng đường huyết, đề kháng insulin
Suy giảm sử dụng oxy hiệu quả	Các loại oxy hoạt tính (ROS - reactive oxygen species)

Englert JA, Rogers AJ.. Clin Chest Med. 2016;37(2):321-331. doi:10.1016/j.ccm.2016.01.011

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Vai trò của amino acid

Nguồn amino acid tự do trong cơ thể được duy trì từ ba nguồn chính:

Sản phẩm thoái giáng từ protein mô,
Amino acid được tổng hợp mới,
Nguồn từ dinh dưỡng đưa vào.

Vai trò của các amino acid :

Được sử dụng để tổng hợp protein mới,
Tham gia điều hòa các con đường chuyển hóa đặc hiệu,
Hoặc bị oxy hóa và đào thải dưới dạng ure.

Preiser, JC., et al. Crit Care 19, 35 (2015). https://doi.org/10.1186/s13054-015-0737-8

Preiser, JC., van Zanten, A.R., Berger, M.M. et al. Metabolic and nutritional support of critically ill patients: consensus and controversies. Crit Care 19, 35 (2015). https://doi.org/10.1186/s13054-015-0737-8

Preiser, JC., et al. Crit Care 19, 35 (2015). https://doi.org/10.1186/s13054-015-0737-8

Protein requirements

The issue of optimal protein intake is no simpler than that of caloric intake. Essentially, the pool of free amino acids is fueled by the degradation products of tissue proteins, de novo synthesized amino acids, and nutritional intake. These amino acids are incorporated into proteins, involved in the regulation of specific pathways, or oxidized and removed as urea. The minimal protein requirement can be defined as the amount required to maintain a neutral tissue protein balance, at least in physiological conditions [58]. During critical illness, however, the breakdown of proteins is markedly increased and the types of protein synthesized differ considerably from healthy conditions. Recently, Rooyackers and colleagues [59] demonstrated that protein synthesis was markedly increased in patients with multiple organ failure. In addition, several pathways potentially regulated by amino acids are activated, and the mechanisms of clearance, including renal function, are often impaired. Therefore, the optimal amount of protein in critically ill patients cannot be deduced from data recorded in healthy subjects.

In critical illness, the loss of lean body mass, together with physical inactivity, is associated with increased proteolysis via the proteasome/ubiquitin pathway [60]. These findings generated the hypothesis that increased protein requirements are related to (a) the need for a greater amount of amino acid to achieve the same muscular synthesis rate, as a result of the anabolic resistance; (b) the need for amino acids for the synthesis of acute-phase response proteins; (c) the need for cysteine, the rate-limiting step of glutathione synthesis, in order to limit oxidative stress [61]; and (d) the prevention of glutamine depletion in muscle and plasma [62,63], and increased utilization [64].

Recent observational data suggested that a large intake of protein (1.2 to 1.5 g/kg per day) was associated with better outcomes in one study and contradictory effects in another [33,34]. In a landmark study, Ishibashi and colleagues [65] showed that 1.5 g/kg per day was associated with the least negative total body protein balance. A protein dosing trial has recently been completed, but until the results are available and in the absence of high-quality prospective trials designed to specifically address the issue of optimal protein intake [66], data from the large interventional trials using supplemental parenteral nutrition can be used to try and provide some answers. Post hoc analyses of the results of three recent trials [7,17,24] suggested better outcomes in patients who received less protein.

The discrepancies between the results of clinical studies suggest that there is no fixed energy-to-nitrogen ratio that could be applied in all physiological and pathological conditions. Ambulatory or exercising patients require a higher energy intake in contrast to bedridden or critically ill subjects. Furthermore, inactivity and systemic inflammation can induce or exacerbate anabolic resistance, itself leading to muscle atrophy, increased fat mass, and decreased metabolic rate.

Biomarkers of optimal protein and amino acid intake include whole body or tissue protein balance, circulating protein or amino acid levels, physiological functions (muscle strength, immune competence, insulin sensitivity, glutathione, and oxidative stress), and ultimately clinical outcome. The use of techniques to assess lean tissue by ultrasound [67] or computed tomography scan [68] could help to more accurately tailor the amount of protein, but this needs to be studied further.

�

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Chuyển hóa protein trong BN NKH

Nhu cầu protein tối thiểu là lượng cần thiết để duy trì cân bằng protein mô trung tính, ít nhất trong điều kiện sinh lý bình thường.
Trong tình trạng bệnh nặng🡪 tăng thoái giáng protein, và thay đổi loại protein được tổng hợp
Tổng hợp protein tăng mạnh ở bệnh nhân suy đa cơ quan.
Nhiều con đường chuyển hóa bị điều hòa bởi amino acid được kích hoạt
Cơ chế loại bỏ amino acid như chức năng thận thường bị suy giảm.

Preiser, JC., et al. Crit Care 19, 35 (2015). https://doi.org/10.1186/s13054-015-0737-8

Preiser, JC., van Zanten, A.R., Berger, M.M. et al. Metabolic and nutritional support of critically ill patients: consensus and controversies. Crit Care 19, 35 (2015). https://doi.org/10.1186/s13054-015-0737-8

Preiser, JC., et al. Crit Care 19, 35 (2015). https://doi.org/10.1186/s13054-015-0737-8

Protein requirements

The issue of optimal protein intake is no simpler than that of caloric intake. Essentially, the pool of free amino acids is fueled by the degradation products of tissue proteins, de novo synthesized amino acids, and nutritional intake. These amino acids are incorporated into proteins, involved in the regulation of specific pathways, or oxidized and removed as urea. The minimal protein requirement can be defined as the amount required to maintain a neutral tissue protein balance, at least in physiological conditions [58]. During critical illness, however, the breakdown of proteins is markedly increased and the types of protein synthesized differ considerably from healthy conditions. Recently, Rooyackers and colleagues [59] demonstrated that protein synthesis was markedly increased in patients with multiple organ failure. In addition, several pathways potentially regulated by amino acids are activated, and the mechanisms of clearance, including renal function, are often impaired. Therefore, the optimal amount of protein in critically ill patients cannot be deduced from data recorded in healthy subjects.

In critical illness, the loss of lean body mass, together with physical inactivity, is associated with increased proteolysis via the proteasome/ubiquitin pathway [60]. These findings generated the hypothesis that increased protein requirements are related to (a) the need for a greater amount of amino acid to achieve the same muscular synthesis rate, as a result of the anabolic resistance; (b) the need for amino acids for the synthesis of acute-phase response proteins; (c) the need for cysteine, the rate-limiting step of glutathione synthesis, in order to limit oxidative stress [61]; and (d) the prevention of glutamine depletion in muscle and plasma [62,63], and increased utilization [64].

Recent observational data suggested that a large intake of protein (1.2 to 1.5 g/kg per day) was associated with better outcomes in one study and contradictory effects in another [33,34]. In a landmark study, Ishibashi and colleagues [65] showed that 1.5 g/kg per day was associated with the least negative total body protein balance. A protein dosing trial has recently been completed, but until the results are available and in the absence of high-quality prospective trials designed to specifically address the issue of optimal protein intake [66], data from the large interventional trials using supplemental parenteral nutrition can be used to try and provide some answers. Post hoc analyses of the results of three recent trials [7,17,24] suggested better outcomes in patients who received less protein.

The discrepancies between the results of clinical studies suggest that there is no fixed energy-to-nitrogen ratio that could be applied in all physiological and pathological conditions. Ambulatory or exercising patients require a higher energy intake in contrast to bedridden or critically ill subjects. Furthermore, inactivity and systemic inflammation can induce or exacerbate anabolic resistance, itself leading to muscle atrophy, increased fat mass, and decreased metabolic rate.

Biomarkers of optimal protein and amino acid intake include whole body or tissue protein balance, circulating protein or amino acid levels, physiological functions (muscle strength, immune competence, insulin sensitivity, glutathione, and oxidative stress), and ultimately clinical outcome. The use of techniques to assess lean tissue by ultrasound [67] or computed tomography scan [68] could help to more accurately tailor the amount of protein, but this needs to be studied further.

�

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Tăng nhu cầu protein trong NKH

Mất khối nạc (lean body mass) + giảm vận động:

🡪 tăng thoái giáng protein thông qua con đường proteasome/ubiquitin

Nhu cầu protein tăng lên là do:

Kháng đồng hóa (anabolic resistance) 🡪 cần nhiều amino acid hơn mới đạt được cùng mức tổng hợp cơ như bình thường.
Tăng Tổng hợp các protein đáp ứng pha cấp (acute-phase proteins)
Cần cysteine giúp giảm stress oxy hóa
Ngăn ngừa sự thiếu hụt glutamine trong cơ và huyết tương cũng như tăng tiêu thụ glutamine trong giai đoạn bệnh

Preiser, JC., et al. Crit Care 19, 35 (2015). https://doi.org/10.1186/s13054-015-0737-8

Preiser, JC., van Zanten, A.R., Berger, M.M. et al. Metabolic and nutritional support of critically ill patients: consensus and controversies. Crit Care 19, 35 (2015). https://doi.org/10.1186/s13054-015-0737-8

Preiser, JC., et al. Crit Care 19, 35 (2015). https://doi.org/10.1186/s13054-015-0737-8

Protein requirements

The issue of optimal protein intake is no simpler than that of caloric intake. Essentially, the pool of free amino acids is fueled by the degradation products of tissue proteins, de novo synthesized amino acids, and nutritional intake. These amino acids are incorporated into proteins, involved in the regulation of specific pathways, or oxidized and removed as urea. The minimal protein requirement can be defined as the amount required to maintain a neutral tissue protein balance, at least in physiological conditions [58]. During critical illness, however, the breakdown of proteins is markedly increased and the types of protein synthesized differ considerably from healthy conditions. Recently, Rooyackers and colleagues [59] demonstrated that protein synthesis was markedly increased in patients with multiple organ failure. In addition, several pathways potentially regulated by amino acids are activated, and the mechanisms of clearance, including renal function, are often impaired. Therefore, the optimal amount of protein in critically ill patients cannot be deduced from data recorded in healthy subjects.

In critical illness, the loss of lean body mass, together with physical inactivity, is associated with increased proteolysis via the proteasome/ubiquitin pathway [60]. These findings generated the hypothesis that increased protein requirements are related to (a) the need for a greater amount of amino acid to achieve the same muscular synthesis rate, as a result of the anabolic resistance; (b) the need for amino acids for the synthesis of acute-phase response proteins; (c) the need for cysteine, the rate-limiting step of glutathione synthesis, in order to limit oxidative stress [61]; and (d) the prevention of glutamine depletion in muscle and plasma [62,63], and increased utilization [64].

Recent observational data suggested that a large intake of protein (1.2 to 1.5 g/kg per day) was associated with better outcomes in one study and contradictory effects in another [33,34]. In a landmark study, Ishibashi and colleagues [65] showed that 1.5 g/kg per day was associated with the least negative total body protein balance. A protein dosing trial has recently been completed, but until the results are available and in the absence of high-quality prospective trials designed to specifically address the issue of optimal protein intake [66], data from the large interventional trials using supplemental parenteral nutrition can be used to try and provide some answers. Post hoc analyses of the results of three recent trials [7,17,24] suggested better outcomes in patients who received less protein.

The discrepancies between the results of clinical studies suggest that there is no fixed energy-to-nitrogen ratio that could be applied in all physiological and pathological conditions. Ambulatory or exercising patients require a higher energy intake in contrast to bedridden or critically ill subjects. Furthermore, inactivity and systemic inflammation can induce or exacerbate anabolic resistance, itself leading to muscle atrophy, increased fat mass, and decreased metabolic rate.

Biomarkers of optimal protein and amino acid intake include whole body or tissue protein balance, circulating protein or amino acid levels, physiological functions (muscle strength, immune competence, insulin sensitivity, glutathione, and oxidative stress), and ultimately clinical outcome. The use of techniques to assess lean tissue by ultrasound [67] or computed tomography scan [68] could help to more accurately tailor the amount of protein, but this needs to be studied further.

�

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Nhu cầu protein ở BN NKH

NC hồi cứu 834 BN người lớn bị NKH/sốc NK tại BV ĐH tuyến cuối
Lượng protein cao hơn trong tuần đầu tiên liên quan đến Tỷ lệ tử vong nội viện thấp hơn�(HR hiệu chỉnh: 0,55; 95% CI: 0,39–0,78; p = 0,001)
Lượng năng lượng cao hơn liên quan đếnTỷ lệ tử vong 30 ngày thấp hơn�(HR hiệu chỉnh: 0,94; 95% CI: 0,90–0,98; p = 0,003)

Cha, J.-K.; et al., Nutrients 2022, 14, 2318. https://doi.org/10.3390/nu14112318

Cha, J.-K.; Kim, H.-S.; Kim, E.-J.; Lee, E.-S.; Lee, J.-H.; Song, I.-A. Effect of Early Nutritional Support on Clinical Outcomes of Critically Ill Patients with Sepsis and Septic Shock: A Single-Center Retrospective Study. Nutrients 2022, 14, 2318. https://doi.org/10.3390/nu14112318

Cha, J.-K.; et al., Nutrients 2022, 14, 2318. https://doi.org/10.3390/nu14112318

The initial nutritional delivery policy for patients with sepsis admitted to the intensive care unit (ICU) has not been fully elucidated. We aimed to determine whether an initial adequate nutrition supply and route of nutrition delivery during the first week of sepsis onset improve clinical outcomes of critically ill patients with sepsis. We reviewed adult patients with sepsis and septic shock in the ICU in a single tertiary teaching hospital between 31 November 2013 and 20 May 2017. Poisson log-linear and Cox regressions were performed to assess the relationships between clinical outcomes and sex, modified nutrition risk in the critically ill score, sequential organ failure assessment score, route of nutrition delivery, acute physiology and chronic health evaluation score, and daily energy and protein delivery during the first week of sepsis onset. In total, 834 patients were included. Patients who had a higher protein intake during the first week of sepsis onset had a lower in-hospital mortality (adjusted hazard ratio (HR), 0.55; 95% confidence interval (CI), 0.39–0.78; p = 0.001). A higher energy intake was associated with a lower 30-day mortality (adjusted HR, 0.94; 95% CI, 0.90–0.98; p = 0.003). The route of nutrition delivery was not associated with 1-year mortality in the group which was underfed; however, in patients who met > 70% of their nutritional requirement, enteral feeding (EN) with supplemental parenteral nutrition (PN) was superior to only EN (p = 0.016) or PN (p = 0.042). In patients with sepsis and septic shock, a high daily average protein intake may lower in-hospital mortality, and a high energy intake may lower the 30-day mortality, especially in those with a high modified nutrition risk in the critically ill scores. In patients who receive adequate energy, EN with supplemental PN may be better than only EN or PN, but not in underfed patients.

�

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Koekkoek W, van Setten CHC. Timing of PROTein INtake and clinical outcomes of adult critically ill patients on prolonged mechanical VENTilation: The PROTINVENT retrospective study. Clin Nutr. Apr 2019;38(2):883-890. doi:10.1016/j.clnu.2018.02.012

NC hồi cứu, BN ICU thở máy ≥7 ngày
Đạm cung cấp trong 7 ngày đầu:

< 0.8 g/Kg/ngày
0.8-1.2 g/Kg/ngày
>1.2 g/Kg/ngày

Outcome chính: tử vong 6 tháng

Chế độ ăn thiếu đạm gia tăng tỷ lệ tử vong

Tỷ lệ tử vong cao nhất ở nhóm cung cấp thiếu đạm (< 0.8 g/Kg/ngày)
Tỷ lệ tử vong 6 tháng thấp nhất:

< 0.8 g/Kg/ngày trong ngày 1-3 và > 0.8 g/Kg/ngày 4-7

Background & aims: Optimal protein intake during critical illness is unknown. Conflicting results on nutritional support during the first week of ICU stay have been published. We addressed timing of protein intake and outcomes in ICU patients requiring prolonged mechanical ventilation.

Methods: We retrospectively collected nutritional and clinical data on the first 7 days of ICU admission of adult critically ill patients, who were mechanically ventilated in our ICU for at least 7 days and admitted between January 1st 2011 and December 31st 2015. Based on recent literature, patients were divided into 3 protein intake categories, <0.8 g/kg/day, 0.8-1.2 g/kg/day and >1.2 g/kg/day. Our primary aim was to identify the optimum protein dose and timing related to the lowest 6 month mortality. Secondary endpoints were ventilation duration, need for renal replacement therapy (RRT), ICU length of stay (LOS) and mortality and hospital LOS and mortality.

Results: In total 455 patients met the inclusion criteria. We found a time-dependent association of protein intake and mortality; low protein intake (<0.8 g/kg/day) before day 3 and high protein intake (>0.8 g/kg/day) after day 3 was associated with lower 6-month mortality, adjusted HR 0.609; 95% CI 0.480-0.772, p < 0.001) compared to patients with overall high protein intake. Lowest 6-month mortality was found when increasing protein intake from <0.8 g/kg/day on day 1-2 to 0.8-1.2 g/kg/day on day 3-5 and >1.2 g/kg/day after day 5. Moreover, overall low protein intake was associated with the highest ICU, in-hospital and 6-month mortality. No differences in ICU LOS, need for RRT or ventilation duration were found.

Conclusions: Our data suggest that although overall low protein intake is associated with the highest mortality risk, high protein intake during the first 3-5 days of ICU stay is also associated with increased long-term mortality. Therefore, timing of high protein intake may be relevant for optimizing ICU, in-hospital and long-term mortality outcomes.

�

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NC hồi cứu trên 423 BN, trong đó có 297 BN NKH, thở máy kéo dài >= 7 ngày.
Cung cấp protein

thấp: <0,8 g/kg/ngày; TB : 0,8–1,2; cao: >1,2

Tthời điểm ngày 1–3 và 4–7 sau nhập ICU
Nhóm sepsis và non-sepsis.

Koekkoek WACK, et al. Clin Nutr. 2019;38(2):883-890. doi:10.1016/j.clnu.2018.02.012

Koekkoek WACK, van Setten CHC, Olthof LE, Kars JCNH, van Zanten ARH. Timing of PROTein INtake and clinical outcomes of adult critically ill patients on prolonged mechanical VENTilation: The PROTINVENT retrospective study. Clin Nutr. 2019;38(2):883-890. doi:10.1016/j.clnu.2018.02.012

Koekkoek WACK, et al. Clin Nutr. 2019;38(2):883-890. doi:10.1016/j.clnu.2018.02.012

Abstract

Background: The optimal nutritional support for critically ill septic patients remains unknown. This study evaluates the associations

of macronutrient intake during the first week of intensive care unit (ICU) admission and long-term clinical outcomes in septic and

non-septic patients. Methods: Prolonged mechanically ventilated patients were retrospectively studied. The association of protein

(low:<0.8 g/kg/d, medium: 0.8–1.2 g/kg/d, high>1.2 g/kg/d) and energy intake (<80%, 80%–110%, 110% of target) during days 1–3

and 4–7 after ICU admission and 6-month mortality was analyzed for septic and non-septic patients separately. Results: A total of

423 patients were investigated. Of these, 297 had sepsis. In the sepsis group, medium protein intake at days 4–7 was associated with

lower 6-month mortality (hazard ratio [HR]: 0.646, 95% confidence interval [CI]: 0.418-0.996, P=0.048) compared with high intake.

In the non-sepsis group, early high and late low protein intake were associated with higher 6-month mortality (HR: 3.902, 95% CI:

1.505-10.115, P=0.005; HR: 2.642, 95% CI: 1.128-6.189, P=0.025) compared with low and high protein intake, respectively. For

energy intake, late energy intake of >110% was associated with decreased mortality in septic patients (HR: 0.400, 95% CI: 0.222-

0.721, P=0.002), whereas in non-septic patients, late medium energy intake (80%–110%) was associated with better survival (HR:

0.379, 95% CI: 0.175-0.820, P=0.014), both compared with low energy intake. Conclusion: Divergent associations of macronutrient

intake were found; early high protein intake in non-septic patients, but not in septic patients, was found to be associated with higher

6-month mortality. (JPEN J Parenter Enteral Nutr. 2020;44:434–443)

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Kết quả NC

Nhóm NKH (Sepsis):
Protein mức TB giai đoạn ngày 4–7 liên quan đến tử vong sau 6 tháng thấp hơn so với nhóm protein cao (HR = 0,646; 95% CI: 0,418–0,996; P = 0,048)
Nhóm không NKH (Non-sepsis):
Protein cao giai đoạn sớm ngày 1–3 → tăng nguy cơ tử vong sau 6 tháng:�(HR = 3,902; 95% CI: 1,505–10,115; P = 0,005)
Protein thấp giai đoạn muộn ngày 4–7 → tăng nguy cơ tử vong:�(HR = 2,642; 95% CI: 1,128–6,189; P = 0,025)