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Table of Contents
REVIEW ARTICLE
Year : 2019  |  Volume : 5  |  Issue : 1  |  Page : 12-16

Protein delivery in critical care


Consultant Critical Care, Department of Critical Care Medicine, Peerless Hospital, Kolkata, West Bengal, India

Date of Web Publication15-Nov-2019

Correspondence Address:
Dr. Rimita Dey
Peerless Hospital, Kolkata, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrnm.jrnm_44_19

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  Abstract 


Evidence suggests that improving the nutritional status has potential to improve the recovery of critically ill patients. Critically ill patients are at high risk of developing malnutrition due to various factors. Patients who develop sepsis, require prolonged ventilation and therefore are also at risk of developing neuromuscular paresis and have a high risk of mortality. Evidence suggests that improving the nutritional status has potential to improve the recovery of critically ill patients. This article deals with the importance of protein delivery in critically ill patients and how to monitor the adequacy of protein delivery.

Keywords: Critically ill, malnutrition, protein


How to cite this article:
Dey R. Protein delivery in critical care. J Renal Nutr Metab 2019;5:12-6

How to cite this URL:
Dey R. Protein delivery in critical care. J Renal Nutr Metab [serial online] 2019 [cited 2019 Dec 13];5:12-6. Available from: http://www.jrnm.in/text.asp?2019/5/1/12/271040




  Introduction Top


Critically ill patients are at high risk of developing malnutrition due to various factors. Patients who develop sepsis, require prolonged ventilation and therefore are also at risk of developing neuromuscular paresis. These factors further increase the chances of dying or developing complications that delay their recovery. The complications may cause prolonged stay in the intensive care unit, delayed liberation from mechanical ventilation, a higher risk of death, increased hospital cost, and impaired physical functioning and quality of life months after intensive care unit (ICU) admission.[1],[3] These observations speak to the importance of developing new strategies to aid in the recovery of the patients and reducing the complications. Evidence suggests that improving nutritional status has the potential to improve the recovery of critically ill patients.

In a study which analyzed 768 patients, 530 (69%) were calorie deficient and 696 (90%) were protein deficient during the whole ICU stay. The correlation coefficient of ICU length of stay was −0.443 and −0.465, and of days on mechanical ventilation of alive patients was −0.338 and −0.392 for calorie and protein deficit, respectively (P<0.001). Infectious complications were also significantly correlated (−0.346 for calorie deficit, −0.298 for proteins, P < 0.001). The mean calorie deficit of the patients discharged alive from the ICU was −2135.62 ± 1918.63, which was less compared with patients who expired (−2564.44 ± 2173.45 [P = 0.027]).[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33] This was also seen in-hospital outcome. The mean calorie deficit of patients discharged from hospital was −2039.36 ± 1888.82, which was less than the patients who expired after discharge from the ICU (−2603.99 ± 2126.53 [P = 0.002]) [Table 1] and [Table 2].[49]
Table 1: Correlation of complications with calorie and protein deficits

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Table 2: Intensive care unit and hospital outcome related to cumulative calorie and protein deficits

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  How Much Proteins are Required? Top


Statistical analysis of existing nutritional databases revealed a relationship between increased nutritional intake and improved clinical outcomes. It was shown that for additional 30 g/day of protein and 1000 cal/day of calories, critically ill patients have reduced infectious complications, shorter duration of mechanical ventilation and reduced mortality. So what are the requirements? After careful review of the published evidence, experts concluded that critically ill patients should receive up to 2.0–2.5 g/kg/day of proteins and receiving up to 80% of the protein that is prescribed is associated with optimal outcomes. The ASPEN guidelines suggest that the protein requirements are expected to be in the range of 1.2–2.0 g/kg of actual body weight per day and may likely be even higher in case of burns or polytrauma patients. Recent INS database shows much lower delivery of proteins in the current practice.


  Are Calories More Important Or The Proteins? Top


In another analysis using the same INS database, it is shown that proteins are more important than the calories. When they controlled for the calorie intake, they could still see a significant reduction in associated mortality when >80% of proteins are delivered compared with <80% (odds ratio [OR] for 60-day mortality, 0.68; 95% confidence interval [CI], 0.50–0.91). In contrast, when they controlled for protein administration, there is no incremental effect of increased caloric administration (OR, 0.89; 95% CI, 0.71–1.12).


  What Is The Current Practice? Top


Emerging evidence suggests that exogenous protein/amino acid supplementation has the potential to favorably affect protein balance and improves the recovery of critically ill patients. In the INS study, most of the protein delivery was from the enteral nutrition formulas (82.5%). An addition of 11.5% coming from parenteral amino acid sources a few from I/V amino acids alone (0.1%) [Figure 1]. There is good evidence now that exogenous amino acids have a positive impact on muscle mass.[48]
Figure 1: Positive response of protein delivery from the enteral nutrition formulas, parenteral amino acid sources and IV amino acids in intensive care unit (ICU)

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  Concerns About Protein Administration Top


There are some concerns about increased mortality in some studies with increasing mortality with increasing nutritional status. Short-term mortality may not be the best outcome used to evaluate the effect of increased protein administration. Measures of muscle mass or function or patient-based performance measures (6 min walk test, measures of handgrip), if possible may be more sensitive to differential amounts of protein intake. Of note, Early versus Delayed Enteral Feeding to Treat People with Acute Lung Injury or Acute Respiratory Distress Syndrome compared goal feeding with trophic feeding and demonstrated no difference in short-term outcomes; however, better-fed patients had a trend toward improvements in long-term physical functional performance. Hence, the application of nutritional scoring systems to identify patients at risk, having a protocol for providing adequate nutritional intake, monitoring of the nutritional delivery, providing supplemental exogenous amino acids/proteins can be done to improve outcomes in the critically ill patients.


  How To Monitor Adequacy Of Protein Delivery? Top


Traditional serum protein markers (serum albumin, prealbumin, transferrin, and retinol-binding protein) are not markers of nutrition status in critical illness and are not recommended. Both mTOR and GCN2 regulate distinct gene, protein, and cell behavior responses that can refiect amino acid availability and might be readily measured in the clinical setting to identify patients who respond to protein therapy. Some investigators have reported the use of cleaved fraction of alpha-actin as a tool to assess protein degradation in humans.

Another tool used to refiect change in total body protein stores is the determination of nitrogen balance. Simply put, this is the difference between nitrogen intake and loss. The majority of nitrogen excretion occurs through the kidneys. Urinary nitrogen excretion typically increases during critical illness, and measuring 24-h urinary nitrogen, either as urea nitrogen (UUN) or total urinary nitrogen (TUN), has been used to determine protein needs. Each has its limitations; UUN seems to underestimate total nitrogen excretion (particularly in the most catabolic patients), and TUN is not widely available. Nevertheless, measuring urinary nitrogen can help us estimate an individual patient's catabolic state and perhaps guide protein administration. The presently recommended range of protein intake is broad, and measurement of urine nitrogen excretion could help us be more precise in our protein prescriptions.


  How to Increase Protein Delivery in Intensive Care Unit? Top


In the modern ICU medicine, the main cause of protein underdelivery in the ICU is related to the frequent interruptions to enteral feeding because of impending or current procedures.[34] To maximize enteral nutrition (EN) delivery, wefirst need to minimize the time patients are nil per oral with protocols that minimize these interruptions [Table 3] and [Table 4].[35] Then, using existing products and strategies, there are several methods by which practitioners can increase protein/amino administration in the ICU setting: using a high-protein enteral formula, adding protein supplements to the existing EN order, implementing novel enteral feeding protocols that include protein delivery enhancement strategies and/or volume-based feeding strategies,[34],[36],[37],[38],[39] and supplementation with parenteral amino acids alone or PN.[40]
Table 3: Protein adequacy in intensive care unit (ICU)

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Table 4: Guideline for administering supplemental protein

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  Protein Delivery In Special Populations Top


Patients with acute kidney injury and not on hemodialysis are a relative contraindication of higher protein supplementation. One needs to carefully ascertain the requirements, the catabolic stress, etc., before prescribing the supplementation proteins.

Another group would be refractory hepatic encephalopathy where benefits have to be weighed against the risks involved. Although sarcopenia in liver disease is a poor prognostic marker, and proteins have a great role in reversing sarcopenia and improving outcomes in liver disease, in refractory encephalopathy clinical judgment should be used before prescribing protein supplements.


  Conclusion Top


While it is difficult to be precise about how much protein critically ill patients require (and likely that amount varies across patient groups and within a patient over time), it is likely that “more” rather than “what” is currently, and suboptimally, being administered will result in improved outcomes for this patient population, especially for nutritionally “high-risk” patients. We encourage practitioners to achieve a minimum of 1.2–1.5 g/ kg/day and a maximum that approximates 2.0–2.5 g/kg/day. While future research clarifies the exact amount of protein required in various case mix groups of ICU patients or strengthens the available evidence that “more is better,” current quality improvement initiatives should work toward improving current practice, and hence current patients receive more protein. This is based on the notion that by waiting for confirmatory evidence or more precise information, current patients are possibly being harmed. Further research should also develop better tools to enable bedside practitioners to monitor optimal or adequate protein intake for individual patients. Finally, exploring the effect of combining protein intake with early mobility/exercise in the ICU setting has the greatest potential for improving the outcomes of survivors of critical illness and warrants further study.

Financial support and sponsorship

Nil.

Confiicts of interest

There are no confiicts of interest.



 
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