Konsenzus Kitajskega združenja za klinično prehrano o prehranski podpori pri bolnikih s COVID-19

CSPEN consensus on nutrition therapy for severe patients with COVID-19 infections

Zhen Yu1*, Ding-Ye Yu2*, Dong-Dong Huang3, Sheng Wang4, a Hu Peng5, b, Yong-Chao Liu6, c, Song-Juan Yan5, a, Hong Xu7, c, Jun-Min Wei8, Guo-Hao Wu9, Chang-Hui Wang10, d, Kai-Ying Yu11, Xiao-Wei Zhang11, Yun Yang11, Liu-Qing Yang11, Kun-Hua Wang12, Juan Kong13, Hong-Xia Xu14*, Huan-Long Qin1*, Han-Ping Shi11*. The Chinese Society for Parenteral and Enteral Nutrition, CSPEN.

1 Department of General Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University

2 Department of General Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University

3 Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University

4 Department of Surgical Intensive Care Unit, Shanghai Tenth People’s Hospital Affiliated to Tongji University

5 Department of Emergency Medicine, Shanghai Tenth People’s Hospital Affiliated to Tongji University

6 Department of Intensive Care Unit, Shanghai Tenth People’s Hospital Affiliated to Tongji University

7 Department of Orthopaedics, Shanghai Tenth People’s Hospital Affiliated to Tongji University

8 Department of General Surgery, Beijing Hospital, Ministry of Health

9 Department of Gastrointestinal Surgery, Zhongshan Hospital, Fudan University

10 Department of Respiration, Shanghai Tenth People’s Hospital Affiliated to Tongji University

11 Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University

12 Department of Surgery, The First Affiliated Hospital, Kunming Medical University

13 Department of Clinical Nutrition, Shenjing Hospital, Chinese Medical University

14 Department of Clinical Nutrition, Daping Hospital, The Third Military Medical University

These authors are now working on the front line to fight COVID-19 at the following medical organizations:

a Shanghai Public Health Center

b Intensive Care Unit of Wuhan Third People’s Hospital

c Intensive Care Unit of Wuhan Jinyintan Hospital

dShanghai Center for Disease Control and Prevention

* These authors contributed equally to this study.

#Corresponding authors:

Han-Ping Shi, MD, PhD, FACS, Departments of Gastrointestinal Surgery / Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, No.10 Tieyi Road，Haidian Dist, Beijing 100038, China; Tel: +86-10-63926985; E-mail: shihp@ccmu.edu.cn

Huan-Long Qin, MD, PhD, Department of General Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai, 200072, China E-mail: hlqin@sjtu.edu.cn

Hong-Xia Xu, MD, PhD, Department of Clinical Nutrition, Daping Hospital, The Army Medical University, Changjiagnzhilu10#, Yuzhong District, Chongqing 400042, China, Tel: +86-23-68757667, Email: hx_xu2015@163.com

Abstract

COVID-19 infections are a new challenge to the world. Severe patients have a significant higher morbidity and mortality compared with non-severe ones. In response, the Chinese Society for Parenteral and Enteral Nutrition (CSPEN) formulated this multidisciplinary consensus, calling on integrate medical nutrition therapy into routine care for COVID-19 infections as follows.

  • Set up NST;
  • Routinely investigate nutritional status;
  • Provide adequate calorie at 15-30 kcal/kg/d and protein at 1.2-2.0 g/kg/d;
  • Adhere to five-step model nutrition therapy;
  • Reduce metabolic and  inflammatory response by limiting energy, intestinal and fluid load;
  • Early implement enteral nutrition, with ONS preference;
  • Emphasize SPN;
  • Select PN and EN formulation on individual base;
  • Address life-threatening complications and comorbidities;
  • Ensure the successful nutritional care.

CSPEN hopes this consensus will also help the other countries in fighting with COVID-19 infections.

Key words: COVID-19 infections; severe patients; nutrition therapy;

As of 11:00 a.m. on February 24, 2020, Chinese officials had recorded 77,262 confirmed cases of COVID-19-associated pneumonia which has been classified as non-severe and severe two categories by Nan-Shan Zhong(1), with a reported 15.7% to 25.5% of severe patients reported in the literature(1, 2), there were 12,130 to 19,702 severe patients. Compared with non-severe patients, severe patients have a higher mortality rate (8.1% vs.1.4%), a higher incidence of complications (pneumonia: 94.8% vs. 76.1%, ARDS: 15.6% vs. 11%, septic shock: 6.4% vs. 0%, acute renal injury: 2.9% vs. 0.1%), require more treatment (intravenous antibiotics: 80.3% vs. 53.2%, oseltamivir: 46.2% vs. 33.8%, systemic corticosteroids: 44.5% vs. 13.7%, mechanical ventilation: 38.7% vs. 0%, immunoglobulin: 32.9% vs. 9.3%), and are more likely to enter the ICU (19.1% vs. 2.4%)(1). This indicates that severe patients are the focus of treatments because of their poorer prognosis. These patients are also more difficult to treat, and consume more manpower, materials and financial resources. COVID-19 infections are a new challenge, and there are no evidence-based therapeutic guidelines to follow. Learning from past experiences in the treatment of influenza, HIV, MERS and SARS(3-5), and following the recommendations of the Academy of Nutrition and Dietetics supporting the integration of medical nutrition therapy into routine care for the HIV population(5), the Chinese Society for Parenteral and Enteral Nutrition (CSPEN) recently formulated a “consensus on nutrition therapy for severe patients with COVID-19 infections” in order to improve the treatment of these patients.

1. Nutrition support teams (NST)

Recommendation 1: Set up NST, which should be routinely involved in the treatment of severe patients

Due to the lack of proven specific treatments, improving immunity, controlling symptoms and providing supportive care remain the main measures for treating COVID-19 infection(6). Nutrition is the key to human immunity, and nutrition therapy should become part of the routine care and a major means for improving the outcome of patients with COVID-19 infection, especially for severe patients(7). The establishment of a NST is considered to be the most effective measure to implement nutrition therapy, which has been shown to effectively shorten the length of stay (LOS) in the hospital, LOS in the ICU and the duration of mechanical ventilation for critically-ill patients(8).

The NST, which should be comprised of clinicians, dietitians, clinical pharmacists, nurses, et al., should become a core of the multidisciplinary team that treats severe patients with COVID-19 infections. In particular, the duty of the NST is to accurately identify the patients at nutritional risk or with malnutrition, to formulate a reasonable nutrition therapy plan, and to monitor and evaluate the effects of the nutrition therapy(9, 10).

2 Nutrition diagnosis

Recommendation 2: Routinely investigate the nutritional status of severe patients and implement a three-stage nutritional diagnostic program (i.e. 1. nutritional screening, 2. nutritional assessment and 3. comprehensive investigation using any validated tools)

Obtaining an accurate diagnosis of the nutrition status is the foundation of nutrition therapy. Before initiating systematic treatment, the nutritional status of all patients with COVID-19 infection should be investigated as a routine(11). The nutrition diagnosis should be carried out step-by-step using any validated tool. Screening should be carried out first to identify “at risk” status, then the nutrition assessment should confirm the diagnosis of malnutrition and grade its severity and the third should be a comprehensive investigation of the physical, physiological and psychological effects of malnutrition (figure 1)(12). It is recommended that the NUTRIC or modified NUTRIC be used for nutrition risk screening(13-15), followed by the SGA(13, 16) or GLIM(17, 18) for nutrition assessment. Clinical observations found that compared with non-severe patients, severe patients have more underlying diseases (37.6% vs. 20.5%), more lung X-ray changes (26.65 vs. 12.5%), higher hematological abnormalities (white blood cells, lymphocytes, platelets and hemoglobin) and more functional impairments (liver function, renal function, lung function)(1, 2). Therefore, it is necessary to perform a third round of diagnosis, i.e. a comprehensive investigation analyzing malnutrition from four dimensions (energy expenditure, stress levels, inflammatory responses, and metabolic status), and also investigating the effects of malnutrition at five levels (body composition, physical fitness, organ function, psychological status, and quality of life)(19).

3. Energy and protein

Recommendation 3: The caloric intake should be 15 to 30 kcal/kg/day, the ratio of energy derived from glucose to that from lipids should be 50%-60%/40%-50%; the protein intake should be 1.2-2.5 g/kg/day, and the nonprotein calorie-to-nitrogen ratio should be 100-150 kcal:1 g.

Fever (87.9% – 98.6%), cough (59.4% – 82.0%), muscle pain and fatigue (44% – 69.6%) are the most common symptoms of hospitalized patients with the COVID-19 infection(1, 20-22). Severe patients have a higher body temperature, more severe shortness of breath, a greater likelihood of having an increased C-reactive protein level (>10 mg/L: 81.5% vs. 56.4%) and procalcitonin level (>5 ng/ml: 13.7% vs. 3.7%), higher levels of inflammatory mediators (IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, TNF) at admission(1, 20-22), and an albumin level that continues to decrease after admission(23). All the above information suggests that the energy expenditure and protein catabolism of severe patients with COVID-19 infections are higher, so their nutrition therapy should be different from that of non-severe patients, particularly with regard to the energy supply and protein content of the diet. Although the daily energy expenditure (EE) of critically-ill patients may exceed 50% of the normal resting energy expenditure (REE), which is equivalent to 36 kcal/(kg·d), studies have found that the REE of most critically-ill patients is normal, which equates to 22-25 kcal/kg/day. Because most critically-ill patients are inactive, the average REE is closer to the total daily energy expenditure (TDEE)(24). Considering the diversity of severe patients, the CSPEN recommends a broad range of energy consumption, from 62.7~125.4 kJ (15~30 kcal/kg/day). Patients with severe malnutrition, obesity, and acute phase disease (within 4 days after entering the ICU) are recommended to gradually increase their energy supply to more than 80% of the estimated energy needs within 3-7 days, starting with 62.7kJ (15 kcal/kg/day)(24-26). The protein supply is different from the hypocaloric energy supply in the acute phase in patients with severe infections, and we emphasize that the early provision of an adequate supply of protein (1.2-2.5 g/kg/day) is necessary. The calories administered to patients on mechanical ventilation can be calculated based on the carbon dioxide production (VCO2) × 8.19. It is recommended that the caloric needs be calculated using an indirect calorimetry metabolic cart system if conditions permit(24-26).

4. The five-step ladder of nutrition therapy

Recommendation 4: Nutrition therapy should adhere to the five-step ladder model, starting from nutritional counseling/dietary modification and increasing step-wise to total parenteral nutrition, following the ‘50% principle’ to ensure a smooth nutrition ladder transition.

In order to standardize the nutrition therapy for severe patients with COVID-19 infection and give full play to the significant dual potential (improving the clinical outcome and reducing costs) of nutrition therapy(27-29), the CSPEN recommends a five-step ladder nutrition therapy model which consists of 1) oral diet nutritional counseling/dietary modification, 2) oral diet plus oral nutritional supplements (ONS), 3) exclusive enteral nutrition (EEN, oral or tube feeding), 4) partial enteral nutrition (PEN) plus partial parenteral nutrition (PPN), and 5) total parenteral nutrition (TPN) (figure 2)(30), complying with the principles of diet priority, oral route priority and enteral nutrition priority.

The first step of nutrition therapy is oral diet nutritional counseling/dietary modification. Artificial nutrition (enteral nutrition, parenteral nutrition) is chosen only when the diet is insufficient; the first choice of nutrition route is the trans-oral approach, such as ONS. Tube feeding is chosen only when the oral intake is insufficient. Enteral nutrition is the first choice of artificial nutrition, and parenteral nutrition is chosen only when enteral nutrition is insufficient. If the treatment lower on the ladder cannot meet 60% of the targeted energy requirement for 2-3 days, the treatment on the next rung of the ladder should be applied. The nutrition ladder transition for severe patients, i.e. the bottom-up and top-down models in the five-steps ladder, should be switched or transitioned smoothly following the ‘50% principle’ , which means that when enteral nutrition can meet 50% of the target demand, parenteral nutrition should be gradually reduced or stopped while enteral nutrition should be gradually increased; when an oral diet can meet 50% of the target demand, enteral nutrition should be gradually reduced or stopped while the oral diet should be increased gradually; conversely, when 50% of the target demand cannot be met, the parenteral nutrition or enteral nutrition must be continued.

5. Metabolic support and inflammation regulation

Recommendation 5: Reduce the metabolic load, suppress the excessive inflammatory response, and maintain homeostasis.

Cytokine storm and hypermetabolism organ failure complex (HMOFC) are serious conditions that occur in association with many infectious or non-infectious diseases such as MERS, sepsis, and malignancy(31-34). Cytokine storm and HMOFC have also been documented in some patients with the new coronavirus infection, and were important contributors to the patients’ deaths. Severe patients have more severe stress reactions, more significant metabolic disorders, higher levels of inflammatory factors, and faster disease changes(1, 20, 22), highlighting the importance of maintaining metabolic homeostasis and regulating inflammatory responses. In addition to traditional antiviral therapy and glucocorticoid therapy, severe patients also need metabolic support and inflammation regulation therapy as follows: (1) Reduce the energy load, providing 10-15 kcal/kg/d or <30%-50% of the target requirement during the severe acute phase, in cases with hemodynamic instability, ARDS, etc.(35-37), (2) Increase the protein and branched-chain amino acids (BCAA) supply, using supplements if necessary, and inhibit catabolism. It is recommended that 1.5-2.0 g (1.8-3.0 g free amino acids)/kg/d(24, 36) be provided to such patients, and the BCAA ratio should be increased to 35%, which can not only significantly inhibit muscle breakdown(38), but also improve insulin resistance(39) and enhance the efficacy of interferon(40), (3) Inhibit excessive inflammation and regulate immune function. The use of N-3 fatty acids in critically-ill patients can reduce the risk of death, infection, and hospital LOS(41), (4) Inhibition of free radicals to reduce peroxidation damage. The intravenous injection of vitamin C at 3~10 g/d significantly reduced mortality and shortened the use of booster drugs and the need for a ventilator in critically-ill patients(42). The administration of vitamin C may become a standard treatment for patients with sepsis(43) and is effective for patients with virus-associated ARDS(44), (5) Reduce the intestinal load by limiting volume overload and enhancing bowel movement, inhibition of endotoxin release into the bloodstream. Apply tropical enteral nutrition early, and add dietary fiber and prebiotics on an individual basis. (6) Reduce fluid load, especially I.V. fluid.

6. Enteral nutrition

Recommendation 6: Early implementation of enteral nutrition (EN), with an emphasis on ONS.

Gastrointestinal dysfunction in patients with COVID-19 infection is relatively rare, and the incidence of diarrhea and vomiting being only 3.7% and 5.0%, respectively(1). It is thus possible to implement enteral nutrition for most COVID-19 patients. Enteral nutrition should be implemented according to the individual’s condition, gradually transitioning from a predigested formula to a whole protein formula or homogenate preparations. Patients with gastrointestinal dyspepsia may benefit from the administration of short peptide or amino acid formulas. Early enteral nutrition (EEN) can regulate the balance of Th17/Treg cells, inhibit the IL-23/IL-17 axis, reduce the clinical severity of sepsis(45), and reduce infectious complications in critically-ill patients. However, it is recommended that EN be delayed for critically-ill patients with uncontrolled shock, uncontrolled hypoxemia and acidosis, uncontrolled upper GI bleeding, gastric aspiration >500 ml/6 h, bowel ischemia, bowel obstruction, abdominal compartment syndrome, or a high-output fistula without distal feeding access(46). When EEN was initiated within 48 hours of admission to the ICU, there was a significant improvement in the clinical prognosis compared to when it was initiated after 48 hours(46). EN is safe and effective in patients with severe pancreatitis within 24-48 hours, which provides more benefit than delayed enteral nutrition(47, 48). ONS should be given if the oral diet fails to achieve 60% of the energy and protein targets, with a recommended daily supplementation of 400-600 kcal in addition to the oral diet(49, 50). Proper EN, such as ONS, shortens the length of hospitalization, reduces the episode costs, and reduces the 30-day readmission risk(27). However, EN alone is typically unable to fulfill the target requirements for critically-ill patients. A multi-institutional, prospective study of 3,390 mechanically-ventilated patients at 201 centers from 26 countries found that EN was started on average 38.8 hours after admission. The majority (74.0%) of patients did not meet at least 80% of their target energy, with only 61.2% of the energy and 57.6% of the protein prescribed being delivered to patients(51). Critically-ill patients prescribed enteral nutrition alone have a higher risk of malnutrition (OR = 3.77, 95% CI = 2.71-5.24)(9). Combining enteral nutrition and parenteral nutrition is more likely to achieve target requirements(52), reduce infectious complications, reduce 30 day death(52, 53), and improve the patient’s nutritional status and clinical outcomes(52, 53).

7. Parenteral nutrition

Recommendation 7: Fully understand the importance of parenteral nutrition, emphasize supplemental parenteral nutrition (SPN), and consider commercial multi-chamber bags first.

Recent studies have found that the vast majority of critically-ill patients do not meet the 60% target requirement(54). Similar to other diseases, the severe patients with COVID-19 infections may be unable to meet the target nutritional requirements via an oral diet and/or enteral nutrition. Even worse, many widely-used antiviral drugs have severe adverse gastrointestinal effects, which may prevent patients from eating or digesting oral nutrition. A negative energy balance (energy deficit) has been shown to increase infectious complications, the length of hospital stay, and duration of time on a ventilator(52, 54), so parenteral nutrition has become a necessary support for severe patients with COVID-19 infections(55). When enteral nutrition cannot meet 60% of the target energy and protein within 48-72 hours, it is recommended that SPN be provided as soon as possible, because it can improve the clinical outcomes and decrease the medical costs(56-59). An all-in-one formula is recommended over multi-bottle infusions, as commercial multi-chamber bags have many advantages(60, 61) although some patients need an individualized, all-in-one parenteral nutrition formula(62). PN is more likely to improve the patient’s nutritional status, and also has a positive effect on disease treatment and successful weaning from a ventilator, helping patients to survive the dangerous acute infection period and promoting their rehabilitation(55, 63). However, it is necessary to monitor the metabolic status frequently and adjust the PN prescription to prevent overfeeding(64).

8. Formulation selection

Recommendation 8: Increase the proportion of lipids and amino acids in the PN while reducing the proportion of glucose. Preferentially, choose medium- and long-chain lipid emulsions, and increase the omega-3 and omega-9 fatty acid content. Choose general formulas for EN, while disease-specific formulas are recommended for patients with coexisting conditions.

The PN formula for severe patients with COVID-19 infections requires an increase in the proportion of lipids and amino acids, and a reduction in the proportion of glucose. Preference should be given to medium- and long-chain lipid emulsions, and there should be an increase in omega-3 and omega-9 fatty acids. Increasing the proportion of fat in the PN solution may increase the success rate of weaning from the ventilator and shorten the mechanical ventilation time. The inclusion of omega-3 fatty acids in PN can significantly decrease the production of inflammatory factors, triglyceride levels, and liver enzymes(65), improve gas exchange, reduce infectious complications, shorten the length of total hospitalization and reduce the ICU stay(66). In addition, the use of PN has shown significant benefits pharmacoeconomically(67). The immune-neutral effects of ω-6:ω-3 = 2.1: 1 can prolong the survival time of transplanted organs, and may similarly protect native organs from stress(68). The above studies suggest that omega-3 fatty acids are beneficial for preventing cytokine storm and HMOFC in severe patients with COVID-19 infections. The addition of alpha-tocopherol can enhance the anti-inflammatory effects of omega-3 fatty acids(69). Omega-9 fatty acids have immune-neutral and low-inflammatory properties, and are rich in alpha-tocopherol. Long-term use of omega-9 fatty acids can increase oxidized glutathione and protect the liver function(70). The injection of antioxidant-free amino acids may be safer for severe patients with COVID-19 infections, and should be considered for those unable to sustain a sufficient intake via other means(71).

  General EN formulations are preferred over disease-specific formations except in those with comorbid or coexisting diseases. For those with diabetes, diabetes-specific food for special medical purpose (FSMP) is recommended. FSMP with a low sugar and high fat content may be a better choice for diabetic patients with respiratory insufficiency. Tumor-specific FSMP may benefit more for patients with advanced cancer(72, 73). Immune-modulated nutritional preparations can theoretically promote the recovery of critically-ill patients(74-77). Dietary fiber, prebiotics, probiotics, etc. have certain effects, including the induction of flatulence, diarrhea, and a microecological balance, they could be used on an individualized consideration, especially for probiotics. Homogenate diets from dark green vegetables, fruits, and beans, are rich of antioxidants such as vitamin C, vitamin E, carotenoids, and selenium can reduce oxidative stress-related damage(78).

9. Nutrition therapy for comorbidities

Recommendation 9: Attention should be paid to nutrition therapy that can address life-threatening complications and comorbidities.

According to the report by Nan-Shan Zhong et al.(1), hypertension (14.9%) and diabetes (7.4%) are the two most common comorbidities. Pneumonia (79.1%) and ARDS (3.4%) are the two most common complications. All other conditions and complications were found in fewer than 3% of cases. However, compared to non-severe patients, severe patients with COVID-19 infections had an older average age (52 yr. vs. 45 yr., P<0.001), more comorbidities (hypertension: 23.7% vs. 13.3%, diabetes: 6.2% vs. 5.7%), and a higher incidence of complications (pneumonia: 94.8% vs. 76.1%, ARDS: 15.6% vs. 1.1%). These observations emphasize that providing nutrition therapy targeting these comorbidities and complications is of great importance in severe patients with COVID-19 infections. The specific indications for these conditions are described below:

  • ARDS: Clinical observations have shown that ARDS is the leading cause of death in severe patients with COVID-19 infections. Nutrition therapy for ARDS follows the general principles of metabolic support and inflammation regulation described above, including inhibiting the inflammatory response, reducing the metabolic load and inhibiting catabolism. It is essential to perform trophic EN(79-81), controlled underfeeding of PN, to provide sufficient BCAA(82), moderate addition of omega-3 fatty acids, and to include dietary fiber. A subgroup analysis within a meta-analysis showed that moderate underfeeding of EN reduced the overall mortality in patients with acute respiratory failure(80). Compared to septic shock patients without EN or those receiving ≥600 kcal/d EN, those receiving EN <600 kcal/d starting within 48 hours of admission had a significantly reduced mechanical ventilation time and ICU hospital stay(81). Short-term (2 consecutive days) oral intake of 14.4 g BCAA significantly improved the respiratory quotient (RQ), while continuous oral intake for 30 days significantly improved the handgrip strength without increasing the oxygen consumption (VO2) and heat production(82). Supplementation of omega-3 fatty acids significantly and continuously improved the PaO2/FiO2 ratio in ARDS patients, and there was also a tendency toward a reduced duration of mechanical ventilation and ICU hospital stay(83).
  • Hypoproteinemia: It has been reported that 83% of severe patients with COVID-19 infections have elevated C-reactive protein levels(84) and 50% of patients had decreased albumin level at admission, with a continuous drop after admission(23). Albumin has a variety of physiological functions, such as maintaining the colloid osmotic pressure, serving as a carrier for a variety of biological substances, scavenging free radicals, being an antioxidant, and anti-platelet aggregation. Hypoalbuminemia may indicate (1) poor nutritional status, (2) reduced antioxidant, anti-free radical, and detoxification capabilities, and (3) severe acute inflammation(85), all of which lead to a poor clinical prognosis. Hypoalbuminemia also alters the pharmacokinetics and pharmacodynamics of albumin-carried drugs, including antibiotics(86, 87). Intravenous albumin infusion has limited efficacy and is associated with many adverse reactions, hence it should be as per individual condition, but not be the first choice of hypoalbuminemia treatment(88). Rather, administering EEN rich in protein provides a better solution(89).
  • Diabetes/Hyperglycemia: Hyperglycemia is a well-known indication of a poor clinical prognosis(90). High glycemic variation (mean amplitude of glycemic excursions (MAGE) >65 mg/dL) within 24 hours of ICU admission is an independent risk factor for an increased 30-day mortality(91). Therefore, the management of blood glucose in critically-ill patients, especially those with diabetes, includes two aspects: blood glucose control and blood glucose stabilization(92). The American Academy of Internal Medicine recommends that the blood glucose of ICU patients be maintained at 7.8-11.1 mmol/L (140-200 mg/dL) but not less than 7.8 mmol/L (<140 mg/dL) with insulin administration(90). Hypoglycemia is also an important cause of death; therefore, the blood glucose levels should be continuously and dynamically monitored to avoid dramatic fluctuations(92, 93).

The average blood glucose concentration and glycemic variability of diabetic critically-ill patients have not been found to have an association with ICU death, which is different from patients without diabetes. Nonetheless, hypoglycemia, with a cutoff point of ≤2.2 mmol/L, is related to ICU death for both non-diabetics and diabetics(93). The cut-off points for low glucose are different for non-diabetics and diabetics, namely 4.9 mmol/L and 3.5 mmol/L, respectively(93).

Nutritious formula with low glucose and high-fat content that is rich in fiber helps control blood glucose, reduce insulin requirements, and lowers the risk of hypoglycemia. Nutrition therapy prescribed by a registered dietitian (RD) plays an important role in diabetes management(94).

(4) Hypertension: Hypertension being the most common comorbidity in patients with COVID-19 infections may be due to its high incidence among the population, rather than being condition-specific. Although the rate of hypertension in severe patients with COVID-19 infections is higher than that of non-severe patients, it may be related to the older age of these patients rather than the disease status. The provision of nutrition therapy for hypertension in severe patients with COVID-19 infections should follow the principles of nutrition therapy for general hypertension patients. This may include but not limited to discarding eating habits that make the subject prone to hypertension, increasing physical activity and increasing plant-based food intake, taking supplemental calcium, magnesium, potassium, folic acid and vitamin D, and reducing homocysteine levels, sodium intake and alcohol consumption(95-97). Nutrition therapy by RD is essential in the management of hypertension.

  1. Nutritional care

Recommendation 10: A prerequisite for ensuring the successful implementation of nutrition therapy is to rapidly detect nutritional deficiencies and treat complications. Attaching great importance to nutritional care and management.

  • Management of PN infusion

            Severe patients with COVID-19 infections usually have a central venous catheter or central venous catheterization via peripheral venipuncture, which can administer fluids at a speed less than 200 mL/h. An intravenous infusion pump is recommended for providing PN. Severe patients with COVID-19 infections are often older and have weaker immunity, and are at high risk for catheter-related bloodstream infections (CR-BSI). A continuous quality improvement plan is an effective measure to reduce CR-BSI(98-100). Such plans should include: (1) paying attention to hand hygiene, (2) avoiding unnecessary intubation, (3) ensuring that there are completely sterile barrier precautions when inserting a tube, (4) performing subclavian vein catheterization, (5) sterilizing skin using 2% chlorhexidine ethanol solution, (6) use a chlorhexidine-containing device to secure the catheter, (7) change wet or loose dressings in a timely manner, (8) remove the catheter as early as possible, (9) use a commercial multi-chamber bag, (10) if there is local redness, swelling, heat, pain or fever of unknown origin, CR-BSI should be considered. The catheter should be removed and a catheter tip culture should be performed. Advanced patient age and long-term retention are independent risk factors for CR-BSI(101).

  • Management of tube feeding for EN 

The nasogastric route should be considered in patients requiring short-term (2-4 weeks) EN. Endoscopic gastro/jejunostomy is recommended for patients requiring tube feeding for more than 4 weeks. The temperature of the EN solution should be maintained at about 40℃. Continuous infusion using an infusion pump is recommended, with a flow rate of 20-30 ml/h at the beginning. If there is no retention after 2 hour, the speed can be increased at a rate of 10 ml/h up to 60-100ml/h. The gastrointestinal feeding tube can be connected with a Hemovac drain to determine whether there is gastric retention.

Suggestions for treating intolerance of EN via a nasogastric tube include: (1) use gastrointestinal stimulants (such as metoclopramide and erythromycin) or narcotic antagonists (such as naloxone and alvimopan), (2) change to post-pyloric feeding.

To avoid aspiration-related pneumonia, it is recommended to (1) raise the head of the bed to a 30-45° angle, (2) patients at high risk of aspiration-related pneumonia or patients with positive pressure ventilation should be given the option of using a nasal jejunal tube or having endoscopic gastro/jejunostomy (PEG/J).

  • Nutritional management of patients on a ventilator

It was reported that 38.7% of severe patients infected with COVID-19 infections require mechanical ventilation(1). Positive mechanical ventilation changes the normal negative pressure in the chest, which indirectly increases the intra-abdominal pressure and significantly weakens diaphragmatic breathing, especially under a high driving pressure or positive end-expiratory pressure. Therefore, nutrition therapy should be carried out step-by-step to determine each individual’s nutritional requirements. The intestinal functions should be carefully monitored until perfusion and oxygenation improves. A top-down strategy for the five-step ladder principle is recommended (PN→PPN+PEN→EN), and the water being provided should be moderately increased(102). A chlorhexidine mouthwash used twice a day can reduce the risk of ventilator-associated pneumonia(25).

Summary

At present, the COVID-19 outbreak has put tremendous pressure on the physical health, mental health and daily life in China as well as the whole world. Huge challenges have been brought to world’s economic development and social order, leading to a massive consumption of human, financial and material resources. In the absence of specific antiviral therapy, and even if/when antiviral therapy becomes available, improving the nutritional status and immunity of individuals are always the most important measures for the prevention and treatment (as well as the recovery from) infectious diseases, including COVID-19 infection. Extensive studies have confirmed that nutrition therapy can significantly improve the therapeutic effects of conventional treatments, shorten the length of stay in both the hospital and ICU, reduce mortality, improve the prognosis of patients and reduce medical costs(27, 28). According to the latest research from the American Society of Parenteral and Enteral Nutrition, nutrition therapy saves 52 million US dollars for patients with sepsis every year, and 580 million US dollars for patients with sepsis, gastrointestinal cancer, nosocomial infections, surgical complications and pancreatitis(29). Therefore, in the war against COVID-19 infection, great importance should be attached to the core position and basic role of nutritional therapy. The nutritional status should be regarded as a basic vital sign(103), and nutritional therapy should be regarded as first-line treatment(104) both for COVID-19 and for the majority of human diseases. The present CSPEN consensus on nutrition therapy for severe patients with COVID-19 infections will benefit not only China but also the whole world and will help not only fighting with COVID-19 infections at present but also other virus infection in the future.

FUNDING

This work was sponsored by the National Key Research and Development Program awarded to Dr. Hanping Shi (No. 2017YFC1309200).

DISCLOSURE

All the authors declare no conflicts of interest.

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