Nutrition of the COVID-19 patient in the intensive care unit (ICU): a practical guidance

COVID-19 is a disease at high risk of malnutrition. The most severe cases are encountered in particular, but not exclusively, in patients with a chronic disease (such as organ failure, obesity with body mass index ≥ 40, type 2 diabetes or cancers), who are elderly, and/or with polypathologies [2, 16]. These diseases often mask underlying protein malnutrition (sarcopenia). Malnutrition is a factor of poor prognosis and should therefore be actively investigated, even in the absence of specific literature concerning COVID-19.

The 2018 international consensus for malnutrition diagnosis by GLIM defined new criteria for the diagnosis of malnutrition [19]. According to the GLIM criteria, a patient is malnourished if he/she has at least one phenotypic criterion and at least one etiologic criterion. Phenotypic criteria are body mass index < 20 (or < 22 if age ≥ 70 years) or weight loss > 5% within past 6 months or > 10% beyond 6 months or reduced muscle mass; etiologic criteria are reduced food intake (≤ 50% in > 1 week or reduced food assimilation (malabsorption or previous history of GI surgery) or acute disease/injury/chronic disease-related inflammation.

In the context of the COVID-19 epidemic, the phenotypic criteria are poorly applicable:

Therefore, the nutritional screening at admission should be based on:

Moreover, two etiologic criteria for malnutrition diagnosis (according to GLIM recommendations [19]) are obvious in the COVID-19 patients:

IC is the reference method to assess the energy requirements in the non-COVID-19 ICU patients [18]. However, in the context of the COVID-19 epidemic, but depending on location, some ICUs experience massive overload of COVID-19 patients. That context precludes the performance of any sophisticated non-vital methods at the early phase of ICU stay. Moreover, there is still an uncertainty regarding the safe use of IC, as the usual decontamination procedures cannot be guaranteed in an epidemic context. Therefore, committed IC devices and virus filters for COVID-19 patients only should be considered when possible. To avoid exposure to aerosol and potential virus contamination during IC device connection/disconnection, our recommendations are, previous to connection to the IC device, to put the ventilator on standby and to clamp the tube, then connect and when connected to declamp the tube and to restart the ventilator. This way is preventing the potential spread of virus during disconnection/connection.

Therefore, in these conditions, we propose that IC should be performed to all patients after 3–4 days in the ICU. Depending on staff organization and material availability, patients staying longer than 10 days in the ICU or those on full PN should be the priority. Indeed, the patients on full PN are the most at risk of developing the serious complications related to overfeeding (hyperglycemia, hypertriglyceridemia, bacteremia, liver injury).

Alternatively, to determine calorie and protein needs, we propose the use of predictive equations according to weight (Fig. 1). Introduction of nutrition support should be phased according to day (Fig. 1). The ultimate goal is to avoid underfeeding or overfeeding.

Importantly, obesity is associated with severe forms of COVID-19. In the ICU, obesity is also associated with increased protein catabolism as compared with non-obese patients [25]. It is therefore even more necessary to avoid restrictive and hypocaloric nutrition in obese patients. Underfeeding is more likely in obese patients: obese patients often have increased energy expenditure compared to non-obese [20]; initiation of nutritional support is often delayed in obese ICU patients [21]. In obese ICU patients, rapid weight loss would be associated with increased loss in muscle mass, weakening the immune defenses and therefore promoting COVID-19 severity.

The RS is underestimated at ICU admission [28]. COVID-19 patients are often vulnerable (old, polymorbid, malnourished, sarcopenic) [29] and frequently unwell for 9–15 days [13, 30], i.e., presenting fever, asthenia, lack of appetite, reduced food intake, leading to energy deficit before their ICU admission. These characteristics promote the risks of electrolyte imbalances (i.e., refeeding syndrome). We propose to detect/prevent the RS in older patients, those with polymorbidity, no/low food intake for > 5 days, preexisting malnutrition, and abnormal electrolytes due to diuretic treatment and dialysis. Plasma potassium, phosphorus, and magnesium should be measured within 6 h after nutrition support is started to detect and treat low values. For refeeding guideline, please refer to the UK National Institute for Health and Care Excellence (NICE) guidelines [31] https://​www.​evidence.​nhs.​uk/​search?​pa=​2&​q=​refeeding+syndro​me.

Specific advices regarding patients under propofol should be stated here. All the sedative drugs, including propofol and benzodiazepines, have immunosuppressive effects [32]. The “propofol infusion syndrome” (PRIS) is a rare complication observed when propofol is used for > 48 h and at high doses (> 4 mg/kg/h) and must be evoked in case of hemodynamic degradation or lactic acidosis without any other causative factor. The monitoring every 72 h of arterial gazometry, plasma lactate, creatine phosphokinase, and triglycerides allows anticipating the risk of PRIS and stop propofol. In the COVID-19, the cytokine storm could lead to hemophagocytosis that could itself increase plasma triglyceride, independently from propofol use. Plasma triglyceride monitoring at least every 72 h is advised in all ICU COVID-19 patients. Moreover, propofol doses should be controlled and alternative sedation should be used if the doses are too high or the treatment is prolonged. Large administration of omega-6 fatty acids is not recommended in the context of strong inflammatory response to virus load.

As usually recommended in the ICU [18, 33], EN should be preferred over PN. A lack of consensus among international academic societies exists about the best timing to start nutrition support after ICU admission. The main reason is the heterogeneity of the ICU patients (age, severity of disease, medical versus surgical cares, preexisting malnutrition, chronic diseases). All over the world, ICU COVID-19 patients are rather similar in terms of vulnerability (older, chronic diseases, low food intake for 5–10 days) [2, 16] and likelihood of prolonged ICU stay on mechanical ventilation [14, 15]. These characteristics support the indication for early (< 48 h after admission) and progressive increase of nutrition support (usually enteral) to reach an energy target by day 4–6 days, depending on tolerance (Fig. 1). This is in line with the main available international guidelines for nutrition during critical illness and COVID-19 [27] https://​www.​nutritioncare.​org/​uploadedFiles/​Documents/​Guidelines_​and_​Clinical_​Resources/​Nutrition%20​Therapy%20​COVID-19_​SCCM-ASPEN.​pdf, https://​www.​auspen.​org.​au/​auspen-news/​2020/​4/​6/​covid-19-information. The polymeric standard EN formulas should be used like in other ICU patients. If polymeric EN administration is associated with diarrhea, semi-elemental EN can be tested as second line. To our knowledge, there is no specific indication for arginine in ICU COVID-19 patients. As a meta-analysis [34] reported that arginine increases mortality in sepsis and pneumonia patients, arginine should not be used in COVID-19 patients.

In the context of ARDS, EN is frequently delivered in the prone position. This is associated with an increased risk of gastroparesis and vomiting. All should be done to optimize EN (Fig. 1). In the context of the use of hydroxychloroquine associated with azithromycin as an antibiotic therapy against the SARS-CoV2 virus, the preferable prokinetics is metoclopramide, to avoid any drug side effect and interferences. EN during prone position has been shown to be safe in terms of large gastric residue, vomiting, or intolerance [35]. The prone position per se does not represent a limitation or contraindication for EN and is recommended by the ESPEN guidelines [18].

According to a meta-analysis [8], 17% of the patients with severe COVID-19 had GI symptoms (95% CI, 6.9–36.7%), in line with other findings [3‐7]. In the meta-analysis, stool samples were positive for SARS-CoV-2 virus DNA in 48.1% of the cases (95% CI, 38.3–57.9%) [8]. However, there is no evidence that COVID-19 patients with recent history of diarrhea, abdominal pain, nausea, and vomiting should be contraindicated to EN. In case of EN intolerance, nutrition delivery should be adapted as described in this section and the “PN is indicated if EN is impossible, contraindicated, or insufficient and should be prescribed using a case-by-case decision making” section. According to the severity of GI symptoms, EN should be temporarily stopped or reduced or combined/switched to supplemental or total PN.

We do not advise the systematic measurement of gastric residual volumes (GRV). In ventilated patients, not measuring GRV was not associated with an increased risk of ventilator-associated pneumonia [36]. ASPEN (https://​www.​nutritioncare.​org/​uploadedFiles/​Documents/​Guidelines_​and_​Clinical_​Resources/​Nutrition%20​Therapy%20​COVID-19_​SCCM-ASPEN.​pdf) and AuSPEN (https://​www.​auspen.​org.​au/​auspen-news/​2020/​4/​6/​covid-19-information) experts are advising measuring GRV for all prone patients, those under vasopressors or with GI COVID-19. However, there is no clear evidence to support this. Therefore, as viral load may be present in gastric contents, the number of GRV measurements should be reduced. GRV may not be measured in those patients with stable hemodynamic or low dose of vasopressors, including those in the prone position. For others, the decisions should be made case by case, in accordance with the usual ICU department protocols.

As usually recommended in the ICU [18, 33], PN is indicated whenever EN is impossible or contraindicated or in addition to EN as long as it is insufficient (supplemental PN).

Many patients are still receiving high-flow nasal cannula (HFNC) therapy or non-invasive ventilation in many centers [39, 40]. From a practical point of view, based on the Chinese experience [39], these patients are almost not fed orally or enterally. Therefore, we could advocate the use of PN arguing that “being fed by PN” is better than “being not fed.” As most severe patients have a central line, PN should be administered through a central venous line. In case there are too many drugs on the central line, peripheral PN could be used.

In the specific context of COVID-19, the use of supplemental PN could be advocated if EN in the prone position is associated with vomiting, in case of severe hypoxemia (PaO₂/FiO₂ < 50 mmHg with FiO₂ > 80%), or in general, in the situation when the gut is not functioning [18, 41] (Fig. 1). In that context, supplemental PN should not be started before day 4 [18].

As a general principle and as the COVID-19 is a new and unknown disease, we also advocate that PN would be prescribed using a case-by-case decision making, always having in mind that PN is at high risk of overfeeding and hyperglycemia over 10 mmol/l that must be avoided [18, 42]. Mild-to-moderate liver injury, including elevated amino transferases, hypoproteinemia, and prothrombin time prolongation, is a sign of severe COVID-19 [10]. Liver function tests should be monitored like in any other ICU patients receiving EN or PN.

A systematic review and meta-analysis on fish oil (FO) enteral supplementation suggests an advantage for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) acid supplementation in ARDS patients in terms of length of ventilation and length of ICU stay, but not mortality [43]. However, these conclusions were based on low-quality studies. A Cochrane analysis found that enteral EPA and DHA may improve oxygenation and length of ventilation and length of stay, but these findings were mainly based on low-quality evidence studies [44]. Negative outcome associated with administration of enteral FO has been only observed when administered in a bolus and with a low protein regimen [45]. The immunoregulator effects of EPA and DHA may have a beneficial impact in the severe cytokine storm observed in SARS-CoV-2 ARDS. Therefore, we suggest that EN enriched with 3.5 g/day EPA and DHA can be administered in this disease, not in a bolus. Higher amounts up to 9 g/day have been administered safely [43].

FO-based intravenous lipid emulsions have been extensively analyzed in a meta-analysis [46] including 49 prospective randomized controlled studies with intervention groups receiving omega-3 fatty acids compared to standard intravenous lipid emulsions (ILEs), as a part of PN covering > 70% of the energy provision. Mortality was not decreased significantly, but a significant decrease was observed in relative risk of infection (40% lower) with omega-3 fatty acid-enriched ILEs, in ICU and in hospital lengths of stay. Risk of sepsis was also reduced by 56%. This latest analysis increases our knowledge on FO-enriched lipid emulsions. If PN including ILEs is required in this population suffering from COVID-19 ARDS, FO-enriched lipid emulsions should be prescribed. The provision of omega-3 fatty acids increases the EPA and DHA plasma levels [47]. The recommended FO doses are 0.1–0.2 g/kg/day.

After extubation, the nutritional strategy must be adapted according to certain situations. After a median of 28 days at hospital [13‐15, 30], patients are likely to be malnourished. In most patients, EN should be continued as patients are transitioned to oral diet but not sufficiently to cover their protein-energy needs. This is critical to enhance COVID-19 recovery. Post-extubation swallowing disorders are frequent—10 to 67% of patients [17]—and at risk of insufficient oral intake, therefore malnutrition. After extubation, approximately 24% of elderly patients require EN in addition to their oral food intake [18]. In the context of the COVID-19 epidemic, this proportion would be expected to be higher, due to prolonged resuscitation and the intensity of the inflammatory and catabolic syndrome.

Based on the ESPEN recommendations [18], we propose the following:

Depending on the individual clinical condition, mobilization at bedside will be encouraged to preserve muscle reserves and function and enhance recovery. It will be adapted to the patient’s capacity for autonomy, in a context of limited availability and access by physiotherapists for priority respiratory care. Mobilization will be intensified as soon as the clinical improvement allows.