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Clinical Infection & Immunity

Case Report

Volume 6, Number 2, June 2021, pages 55-59

Daily Energy Requirements and Substrate Utilization in Hyper- and Hypometabolism of Obese COVID-19 Patients Measured by Indirect Calorimetry: Two Case Reports

One of the biggest challenges imposed on humanity and health systems widespread so far this century is coronavirus disease 2019 (COVID-19) pandemic. Diabetes, hypertension and obesity are the most important comorbidities listed [1]. Indeed, obesity is an independent factor of high risk of mortality in COVID-19 [2, 3]. However, despite the belief that critically ill obese patients with COVID-19 have an increased resting energy expenditure (REE), in some specific obese patients, an apparently contradictory reduction in metabolic needs is observed, i.e., hypometabolism. In any situation, the nutrition support assessment should be guided by indirect calorimetry (IC) to account for the daily changes in metabolic demand to avoid under or overfeeding, a deleterious stressful clinical condition with outcome implications [3-5].

We present a report of two cases of COVID-19 obese patients admitted to an intensive care unit (ICU). Data were collected and IC (M-COVX gas exchange monitor, CARESCAPE R860^®, GE Healthcare, Chicago, IL, USA) was performed over a period of 8 consecutive days (D1 - D8). The results were obtained in steady state, without leakage in the breathing circuit (closed circuit) and, with less than 10% of fluctuations throughout the day. The M-COVX module can display measured REE (mREE) using the modified Weir equation [6]:

mREE (kcal/day) = (5.5 × VO₂ + 1.76 × VCO₂) - (1.99 × UN),

The predicted REE (pREE) was calculated bellow by the classic Harris-Benedict equation using actual body weight and height at ICU admission.

Males: pREE (kcal/day) = 66.5 + 13.8 × weight (kg) + 5.0 × height (cm) - 6.8 × age

Females: pREE (kcal/day) = 655.1 + 9.6 × weight (kg) + 1.8 × height (cm) - 4.7 × age

The calculation of daily substrate utilization (in kcal) was based on modified Weir’s equation as follows:

Carbohydrates: (5.93 × VCO₂ - 4.19 × VO₂ - 2.54 × UN) × 4.18

Lipids: (2.43 × VO₂ - 2.43 × VCO₂ - 1.94 × UN) × 9.46

Protein: (6.25 × UN) × 4.32

None of these two patients was febrile during the IC measurements (D1 - D8), and were sedated (benzodiazepines, opioids, dexmedetomidine and neuroblockers if necessary) according to an established protocol used in our institution for critically ill COVID-19 patients. Hence, both patients were receiving enteral nutrition (16 - 22 kcal/day and 1.5 - 2.0 g protein/kg) prior to the IC measurements, then the energy intake was adapted to the mREE from D1.

The demographic and metabolic data for both cases are visualized in Table 1.

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Table 1. Demographic and Metabolic Data of Case 1 (Hypothyroidism) and Case 2 (Polytrauma)

A 16-year-old female, with a medical history of clinical hypothyroidism, class 3 obesity, 120 kg of body weight and 164 cm of height (body mass index (BMI) = 44.6 kg/m²) was admitted to ICU with severe respiratory distress and a profound compromised in oxygen saturation (SpO₂ = 75%), despite high O₂ mask concentration. Because of a rapid respiratory and chest tomography deterioration associated to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection positive test (reverse transcriptase-polymerase chain reaction (RT-PCR)), the diagnosis of COVID-19 was made. The patient was intubated and placed under invasive mechanical ventilation with an initial fractional inspired oxygen concentration (FiO₂) of 0.6. The pressure of arterial oxygen (PaO₂)/FiO₂ on D1 was 207. The Simplified Acute Physiology Score 3 (SAPS 3) at admission was 41 with a death risk of 10.4%. The C-reactive protein (CRP) and the blood lactate level were 1.9 mg/dL and 0.9 mmol/L, respectively at ICU arrival. Clinical history reported that the patient was without her usual oral treatment of 300 µg of levothyroxine for the last 3 months. The thyroid stimulating hormone (TSH) level was 182.19 µIU/mL (reference value: 0.48 - 4.17 µIU/mL). A referral for endocrinologist was made on D1 and it was prescribed 150 µg of levothyroxine/day via tube feeding in ICU. The TSH level started dropping slowly to 121.84 µIU/mL, 28 days later.

The calculated pREE was 16.9 kcal/day. The daily mean mREE on D1 was 9.7 kcal/day (-42.9% of pREE). The daily mean mREE remained below the pREE throughout the period of study. The 8-day evolution of daily mREE is depicted in Figure 1. Table 2 shows the main daily substrate utilization for this hypometabolic state. The respiratory quotient (RQ) remained steady from D1 to D8, whereas the lipid was the main substrate utilized throughout the study, reflecting a continuous neoglucogenesis with an apparent stability from D8.

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Figure 1. Predicted resting energy expenditure (pREE) calculated by Harris-Benedict equation and mean daily REE measured by indirect calorimetry (measured REE) in kcal/day of hypometabolic (case 1) and hypermetabolic (case 2) obese COVID-19 patients. COVID-19: coronavirus disease 2019.

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Table 2. Mean Daily Substrate Utilization in Kcal/Day (and Percentage) of Carbohydrates, Lipids, Protein With Their Corresponding Respiratory Quotient (RQ), During the 8-Day Period of Continuous Indirect Calorimetry (D1 - D8) in Case 1 (Hypothyroidism)

After an ICU stay of 35 days, there was a progressive improvement in her respiratory functions (FiO₂ = 0.35; PaO₂/FiO₂ = 291), the sedation was stopped and the patient was weaned. Two days later, she was discharged from ICU to an endocrinology hospital ward for further thyroid function investigation.

A 42-year-old male, with a medical history of polytrauma followed by a motorcycle accident, class 2 obesity, 107 kg of body weight and 171 cm of height (BMI = 36.6 kg/m²) was admitted to ICU directly from emergency unit of hospital. In the early phase of hospitalization the patient presented a SARS-CoV-2 infection positive test (RT-PCR) and chest tomography compatible with COVID-19. The patient was already intubated and ventilated because of his severe clinical condition. The FiO₂ and PaO₂/FiO₂ at ICU arrival were 0.35 and 200, respectively. In the first day of admission to ICU the SAPS 3 was 76 with death risk of 80.8%. The CRP was 2.53 mg/dL and blood lactate level was 1.2 mmol/L, remaining stable during the entire study period. The calculated pREE was 19.7 kcal/day. The daily mean mREE on D1 was 20 kcal/day (+1.6% of pREE). However, the daily mean mREE increased to +33.7% of pREE on D5, decreasing to a lower level of +2.1 on D8. The mREEs throughout the study (D1 - D8) are visualized in Figure 1. Table 3 shows the main daily substrate utilization for this hypermetabolic state. The carbohydrate utilization seems to be predominant throughout the study, reflecting a theoretical carbohydrate oxidation (glycolysis) and high RQ, especially in the early period of measurements, reaching the highest value on D2, and then falling progressively. Conversely, the lipids utilization (neoglucogenesis) had an opposite behavior, rising until D8.

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Table 3. Mean Daily Substrate Utilization in Kcal/Day (and Percentage) of Carbohydrates, Lipids, Protein With Their Corresponding Respiratory Quotient (RQ), During the 8-Day Period of Continuous Indirect Calorimetry (D1 - D8) in Case 2 (Polytrauma)

There was an improvement in his respiratory functions on D8 (FiO₂ = 0.23; PaO₂/FiO₂ = 355). The patient was tracheostomized on day 21 of his ICU stay. After a long ICU stay of 32 days, he was discharged from ICU to a general hospital ward for follow-up by the rehabilitation and physiotherapy department.

The longitudinal hypermetabolic response and, consequently, the REE to COVID-19 was not yet entirely described. However, it seems that the continuous high extension of inflammation per se could be a major feature of high REE in COVID-19 infection. Indeed, understanding the REE in COVID-19 infection is crucial to establish safe and optimal needs of nutritional therapy for these patients, and to avoid under/overfeeding which is undoubtedly associated with increased ICU mortality. Hypermetabolism has been widely described in various clinical situations such as sepsis, trauma, acute respiratory distress syndrome, severe burn injury [7] and, more recently, COVID-19 [8]. Despite the belief that critically ill obese patients with COVID-19 have an increased REE [9], in some specific obese patients, an apparently contradictory reduction in metabolic needs can be observed. Indeed, hypometabolism certainly occurs in critically ill patients under heavy sedation or using neuromuscular blockers, genetic differences, neurologic diseases, hypothermia and metabolic disorders such as thyroid dysfunctions may have significant reductions in energy demands compared with other patients [10]. It is generally accepted that REE is increased in thyrotoxicosis and reduced in hypothyroidism but quantitative data on metabolic rate changes are scarce, especially in COVID-19. Despite this uncertainty, minimal changes in thyroid hormones signaling cause considerable perturbation in REE [11].

In the ICU, obesity is also associated with increased protein catabolism compared with non-obese patients. Moreover, underfeeding is more likely in obese patients with a rapid loss in muscle mass and body weight and therefore REE is different in obese patients compared to non-obese [12]. American Society for Parenteral and Enteral Nutrition (ASPEN)/European Society for Clinical Nutrition and Metabolism (ESPEN) recommend for all classes of obesity where BMI > 30 the target of daily energy requirements is 11 - 14 kcal/kg of actual body weight, and protein intake level should be provided at ≥ 2.0 g/kg [5, 6]. ESPEN states that energy requirements can be assessed in COVID-19 infection using IC, if safely available with ensured sterility of the measurements system [13]. This technique should be considered, whenever feasible, to assure more accurate assessment of REE and guide the daily energy intake in COVID-19 patients admitted to ICU. Notwithstanding these recommendations, both obese COVID-19 patients reported in our study presented different metabolic patterns. Case 1 (the hypometabolic one) showed an energy requirement sustained of approximately 10 kcal/kg/day (-41% of basal energy requirements), whereas case 2 had a hypermetabolic state with a REE close to 23 kcal/kg/day (+10.5% of basal energy requirements). It was clear that IC had been an excellent tool to assess the energy requirements for both patients. Thus, nutrition support regimens should provide calories equivalent to energy expenditure. We reinforce that without IC, both cases would be fed equally, according to international guidelines, with a major risk for overfeeding in case 1.

Our study has some limitations, mainly due to the retrospective analysis and the number of patients studied. Nevertheless, these findings are the first stage for further researches. To our knowledge, this is the first description of longitudinal (8 days) mREE in a COVID-19 ICU hypometabolic patient caused by hypothyroidism compared to the expected already described hypermetabolism. The increased energy requirements in the hypermetabolic and reduced in hypometabolic patients were demonstrated by the use of continuous IC measurements during 8 consecutive days. In addition, the use of IC can avoid the pitfalls of predicting REE equations culminating in under or overfeeding.

Acknowledgments

None to declare.

Financial Disclosure

The authors received no specific funding for this work.

Conflict of Interest

None to declare.

Informed Consent

Since the reports of these two cases were described on a retrospective basis, the consent form was waived by Research Ethics Committee of Ribeirao Preto Clinics Hospital (Protocol HCRP 7076/2016). However, the patients gave their permission to be included in this report.

Author Contributions

Dr. Basile-Filho conceptualized the study for publication, wrote the initial draft, and made technical review after Dr. Puga and RD. Malek-Zadeh gave suggestions and also collected and analyzed together with Dr. Basile-Filho the 24-h indirect calorimetry data. PTs. Mazzoni, Siansi, Chedid and da Silva collected and analyzed together with Dr. Basile-Filho the 24-h indirect calorimetry data. PT. Lago found educational benefits of this relevant data and original clinical observation.

Data Availability

The datasets generated during and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

REE: resting energy expenditure; IC: indirect calorimetry; ICU: intensive care unit; CRP: C-reactive protein; TSH: thyroid stimulating hormone; RQ: respiratory quotient

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