key: cord-0816565-3z4qpb22
authors: von Renesse, Janusz; von Bonin, Simone; Held, Hanns-Christoph; Schneider, Ralph; Seifert, Adrian M.; Seifert, Lena; Spieth, Peter; Weitz, Jürgen; Welsch, Thilo; Meisterfeld, Ronny
title: Energy requirements of long-term ventilated COVID-19 patients with resolved SARS-CoV-2 infection
date: 2021-06-29
journal: Clin Nutr ESPEN
DOI: 10.1016/j.clnesp.2021.06.016
sha: fea11d80ae144aa28dc028ef538e407b4288a006
doc_id: 816565
cord_uid: 3z4qpb22

Background & Aims Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can rapidly progress into acute respiratory distress syndrome accompanied by multi-organ failure requiring invasive mechanical ventilation and critical care treatment. Nutritional therapy is a fundamental pillar in the management of hospitalized patients. It is broadly acknowledged that overfeeding and underfeeding of intensive care unit (ICU) patients are associated with increased morbidity and mortality. This study aimed to assess the energy demands of long-term ventilated COVID-19 patients using indirect calorimetry and to evaluate the applicability of established predictive equations to estimate their energy expenditure. Methods We performed a retrospective, single-center study in 26 mechanically ventilated COVID-19 patients with resolved SARS-CoV-2 infection in three independent intensive care units. Resting energy expenditure (REE) was evaluated by repetitive indirect calorimetry (IC) measurements. Simultaneously the performance of 12 predictive equations was examined. Patient’s clinical data were retrieved from electronic medical charts. Bland-Altman plots were used to assess agreement between measured and calculated REE. Results Mean mREE was 1687 kcal/day and 20.0 kcal relative to actual body weight (ABW) per day (kcal/kg/day). Longitudinal mean mREE did not change significantly over time, although mREE values had a high dispersion (SD of mREE ±487). Obese individuals were found to have significantly increased mREE, but lower energy expenditure relative to their body mass. Calculated REE showed poor agreement with mREE ranging from 33-54%. Conclusion Resolution of SARS-CoV-2 infection confirmed by negative PCR leads to stabilization of energy demands at an average 20 kcal/kg in ventilated critically ill patients. Due to high variations in mREE and low agreement with calculated energy expenditure IC remains the gold standard for the guidance of nutritional therapy.

Since its first outbreak in December 2019, the worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was paralleled by increasing hospitalization and ICU admission of coronavirus disease 2019 (COVID- 19) patients.

In 5 to 12% of COVID-19 infections, intensive care unit (ICU) admission is necessary, mostly due to respiratory failure [1,2]. Among ICU patients with COVID-19, up to 91% require invasive mechanical ventilation [3] .

More than 60 % of severely and critically ill COVID-19 patients have a high nutritional risk, which is accompanied by an increased ICU admission rate and in-hospital mortality [4, 5] . These findings substantiate the necessity of adequate nutritional support during every stage of hospitalization.

In-depth knowledge of COVID-19 patient's energy demands along their clinical course is essential to provide adequate nutritional therapy. Current data on the timecourse dependent metabolic phenotype of patients suffering from SARS-CoV-2 infection are sparse and focusses on patients with an acute infection requiring mechanical ventilation [6, 7] . Currently to our knowledge no study investigates energy requirements in COVID-19 patients after resolution of SARS-CoV-2 infection and post-COVID-19 patients respectively.

The European Society for Clinical Nutrition and Metabolism (ESPEN) recommends to determine COVID-19 critically ill patients' energy demands using indirect calorimetry (IC) [8] . The American Society for enteral and parenteral nutrition (ASPEN) states that although IC can ideally determine energy requirements in COVID-19 patients it bears the risk of potential contamination and exposition of healthcare providers to increased viral loads. The society recommends the use of weight-based equations instead [9] . A predictive equation recommending 20 kcal/kg/day can be used and 80 to 100 % of target energy supply should be reached by day 4 [8, 10] [13] . RT-PCR was performed every other day. Patients were considered SARS-CoV-2 negative when two consecutive RT-PCR showed cycle threshold values ≥ 30. Nevertheless, special precautions were undertaken to minimize risks of SARS-CoV-2 transmission, including apnea mode and tube clamping during connection and disconnection [11] .

Patients on extracorporeal membrane oxygenation (ECMO) were excluded from our study. IC was performed every other day. When the patient's respiratory condition was unstable IC was skipped. From January 11 th 2021 to February 21 st 2021 twentysix consecutive patients meeting the inclusion criteria were included in the final analysis. Relative mREE was defined as mREE in kcal per kg ABW. In our study we used predictive equations that have been established for use in critically ill patients.

Equations derived from healthy adults (Harris-Benedict [14] , Owen [15] , and Mifflin St. Jeor [16] ), from hospitalized ventilated and spontaneously breathing patients J o u r n a l P r e -p r o o f (Ireton-Jones 1997 [17] ), or critically ill (Penn State [18] , and Swinamer [19] ). The complete equations are listed in Supplementary Table 1. Mean of differences was calculated as mean of pREE subtracted from mREE.

Percent difference was defined as the difference divided by measurements mean.

Absolute difference and absolute percent difference were calculated with the respective absolute values. Agreement was defined as prediction between 85% and 115% of patient's mREE, and calculated as mean pREE divided by mean mREE.

Demographic data, medical records, scores, comorbidities, laboratory findings, arterial blood gas analysis, ventilator settings, calorimetry results, and clinical outcomes were retrieved from patient's electronic medical charts.

Demographic and medical data following normal distribution were represented as mean ± standard deviation (SD). Data with a skewed distribution were presented as median and interquartile range (IQR). Categorical variables were described as frequency rates and percentages. Student's t-test was performed for continuous parameters. P-values < 0.05 were considered statistically significant. Bland-Altman plots were conducted as described previously [20] . All analyses were performed using R software (The R Foundation, http://www.r-project.org, version 4.0.0) and

GraphPad Prism (GraphPad Software, Inc. version 8).

Baseline characteristics from 26 patients are shown in Table 1 . Among included individuals 18 were male (69.2%), the median age was 62.4 years and median length of mechanical ventilation until isolation for SARS-CoV-2 was suspended was 17.3 days. 68 % of patients showed significant comorbidities (≥ 2). 57.7 % were obese (BMI ≥30 kg/m 2 ). At the end of the study period ICU mortality rate was 20 % (n=5), 48 % of patients were transferred to skilled nursing facilities under mechanical ventilation, and 32 % remained under intensive care.

105 IC measurements from 26 COVID-19 ICU patients after cessation of isolation are summarized in Figure 1 and Table 1C . The mean number of measurements per patient was 4 (± 3). Overall mean mREE was 1687 kcal/day with a standard deviation of ± 487 (Tab. 1C). Mean mREE normalized to bodyweight was 20.0 kcal/kg/day (± 5.52). Total mREE and relative mREE did not change significantly throughout the measurement period ( Fig. 1A & 1B) . Obese individuals (BMI ≥ 30 kg/m 2 ) have a higher risk for malnutrition and a lower basal metabolic rate relative to their body weight. Therefore, we compared absolute and relative energy expenditure of obese and non-obese patients. Indeed, the total mREE of obese individuals was significantly higher compared to non-obese patients' mREE, while mREE relative to body weight was significantly lower in the obese group (Fig. 1D & E) .

To validate equation precision, we calculated pREE for all 105 measurements using and 131 kcal/day (Penn State (HB)), a substantial discrepancy between calculated and measured resting energy expenditure in individual measurements led to poor agreement between mREE and pREE for all tested equations (Tab. 

Hypercaloric nutrition has been shown to be partly responsible for excessive carbon dioxide production (VCO 2 ) in mechanically ventilated patients [23] [24] [25] . Our data suggest that strong adherence to nutrient prescription according to measured energy requirements might alleviate detrimental hypercapnia in COVID-19 patients by preventing overfeeding.

Limitations COVID-19 can rapidly deteriorate into severe hypoxemia and hypercapnia requiring escalation of respiratory support from inspiratory oxygen fraction (F i O 2 ) > 70%, increasing positive end-expiratory pressure (PEEP) adjustment, nitric oxide use, and culminating in the necessity of ECMO, which renders measurement infeasible.

Disrupting the ventilator circuit may further worsen patient's respiratory condition.

Furthermore, IC is inaccurate in high F i O 2 ranges [26, 27] . Measuring a patient's energy requirement on ECMO is challenging since gas exchange occurs by the patient's native lung and by the ECMO device. This needs sophisticated settings that are currently applicable for research purposes only [28] .

Our study presents data from three independent intensive care units in a single clinic from a retrospective cohort of COVID-19 patients. Larger studies are warranted integrating long-term IC measurements starting from pre-ICU, over acute phase to convalescence phase to understand metabolism and changes in energy requirements during the COVID-19 disease course. 

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