Approximately, all admitted hospitalized patients are taking maintenance fluids which mostly contains 5 g/dl of dextrose. Dextrose 5% with or without saline and regardless of saline concentration, is an osmolarity modifier and a source of calories even though it is insignificant when an average volume of maintenance fluids is administered for hospitalized patients (≈2000-3000 ml/day). Although oral dextrose and other carbohydrates yield 4 Cal/g, dextrose IV yields around 3.4 Cal/g due to its monohydrate form [1,2].

Although an insignificant calorie (170-340 Cal/day) are yielded from dextrose saline maintenance fluids, it may be a significant source of non-nutritional calories (NNC) in mal-nourished hospitalized patients who are on parenteral nutrition support when the NNC is not subtracted from the estimated total calorie (TC) requirements [3,4].

In this case, the NNC from dextrose maintenance fluids may cause excess calories- associated hypercapnia which is numerically translated into respiratory quotient (RQ) value exceeds 1. Overfeeding associated hypercapnia has a variety of significant clinical and economic consequences in clinical practice, especially in critically ill patients, including but not excluded to, persistent hypercapnia, hyperglycemia and insulin resistant, initiating or exacerbation non-alcoholic fatty liver diseases (NAFLDs) ventilator weaning trying failure and subsequently emerging of multi-drug-resistant bacteria (e.g., MDR-Pseudomonas. Aeruginosa, MDR-Acinetobacter. Spp and carbapenem resistant Enterobacteriaceae), longer overall hospital admission days and perhaps increased overall mortality rate [5,6].

The aim of this study is to investigate the biochemical and clinical impacts of dextrose saline maintenance solution’s non-nutritional calories in mal-nourished mechanically ventilated critically ill patients who are nutritionally supported by total parenteral nutrition.

An observational retrospective study was conducted in our critical care unit in King Hussein Medical Center (KHMC) at Royal Medical services (RMS) in Jordan between Apr 2017 to Jan 2020 after approval by our Institutional Review Board (IRB) committee. Our single-study study was pursued on 118 eligible TPN dependent mal-nourished mechanically ventilated critically ill patients admitted to our adult ICU via the emergency department (ED) or via other hospital wards with any medical or surgical problem, after 1003 patients were excluded from a total 1121 patients because they either discharged, discontinued TPN, died within first week of Intensive Care Unit (ICU).

A consent form was waived owing to the study retrospective design. All eligible investigated patients were stratified into four tested groups based on PaCO2 level; Group I (Eucapnic Critically ill patients with PaCO2 level of 35-45 mmHg), Group II (Mild hypercapnic Critically ill patients with PaCO2 level of 45.1-50 mmHg), Group III (Moderate hypercapnic Critically ill patients with PaCO2 level of 50.1-59.9        mmHg) and Group IV (Severe hypercapnic Critically ill patients with PaCO2 level of > 60 mmHg).

All patient’s analyzed data were either expressed as mean± SD by using one-way ANOVA Test for parametric data followed by Tukey Kramer Post Hoc test to determine the mean differences of significant dependent variables between each group of the four tested groups or as numbers with percentages by using Chi Square Test for categorical non-parametric variables of gender, Cal level and incidences of hypercapnia occurrences. Statistical analyses were performed using IBM SPSS ver. 25 (IBM Corp., Armonk, NY, USA) and P-values ≤0.05 were considered sta­tistically significant.

One hundred and eighteen mal-nourished mechanically ventilated critically ill patients were included in this observational retrospective study. Our tested patients had an average age of 57.88±9.01 years in which 72.0% (85 patients) and 28.0% (33 patients) were male and female, respectively. The total non-nutritional calories (NNC) were significantly highest in severe Hypercapnic group and lowest in Eucapnic group with Mean±SD of (442.1±15.6 Cal/day and 252.7±57.2 Cal/day) and Mean diff±SEM of -189.39±19.73 Cal/day, respectively. 

From NNC, calories from dextrose saline (Gluc IV_NNC) were also significantly in Hypercapnic group and lowest in Eucapnic group with Mean±SD of (19.6%±1.4% and 10.5%±3.9%) and Mean diff±SEM of -9.1%±1.2%, respectively. The overall risk of dextrose saline maintenance fluids associated hypercapnia regardless of severity in our tested critically ill patients was 74.58% (88 patients) in which 27.12%, 24.58% and 22.88% of the hypercapnic patients had mild, moderate and severe hypercapnia status, respectively.

Consequently, ventilation free days (VFDs) was significantly highest in Eucapnic patients’ group (Group I) followed by mild Hypercapnic (Group II), moderate Hypercapnic (Group III) and severe Hypercapnic (Group IV) with Mean±SD of 3.83±1.93 days, 3.31±2.40 days, 1.379±2.11 days and 0.00±0.00 days, respectively. Numerically, the VFDs Mean diff±SEM was 3.83±0.50 days between Group I and Group IV. Comparison data of the study’s critically ill patients which were analyzed by One-Way ANOVA/Chi Square tests and Tukey Kramer post-hoc multiple comparison analysis are fully summarized in Table 1 and Table 2, respectively.

Table 1: Comparison data of the study’s critically ill patients

Table 2: Multiple comparison of the significant dependent variables between the four tested groups

This retrospective observational study investigated the clinical impacts of non-nutritional sources of calories from dextrose saline maintenance fluids in TPN dependent mal-nourished mechanically ventilated patients. In this study, we assess both the nutritional calories (NC) and non-nutritional calories (NNC) from TPN with or without trophic enteral nutrition (EN) and from dextrose saline maintenance fluids regardless of saline concentration.

Metabolically, carbohydrate has the highest macronutrient’s respiratory quotient (RQ) value compared with the two other macronutrients yielding energy of protein and lipid. Mathematically, RQ is calculated by multiplying each macronutrient proportion of energy from the total energy input by its RQ value which are 1, 0.8 and 0.7 for carbohydrate, protein and lipid, respectively. Expect in certain circumstances, it is optimally to provide 50-60% of calories from carbohydrates, 20-30% from lipid and 10-20% from protein to balance the overall nutrition input in RQ range of 0.8-0.9. Clinically, if the calories from all daily carbohydrate sources are not exceeded the 60% of total energy input (TCI), the risk of overfeeding associated hypercapnia is low, as long as, the TCI is also not exceeded the total energy requirement (TCR) [7].

Practically, the %NNC may exceed 25% of TCR in some critical case scenarios of using other NNC sources (e.g., propofol and clevidipine) in addition to standard dextrose saline maintenance fluids. The relationships between NNC, NC, TCI, TCR and PaCO2 and risk of hypercapnia in mechanically ventilated critically ill patients are complex and many studies mention the strong correlation between NNC from glucose IV and risk of overfeeding associated hypercapnia [8].

Nutritionally, when TPN or EN or both nutritional supports are advancing to achieve the target TCR, the risk of excess calories associated CO2 overproduction may also increase when the total NNCs are not taking into consideration, especially in mechanically ventilated critically patients for which propofol and clevidipine are also commonly used.

Globally, the incidences of MDR bacteria of Acinetobacter, Pseudomonas and Enterobacteriaceae are exponentially increased and as known as the PaCO2 level is increased, the weaning probability from ventilator and VFD are decreased and subsequently the risk of MDR bacteria are also increased. In our study, we investigate the significant contribution of dextrose saline maintenance fluids in the risk of ventilator weaning failure associated hypercapnia and its clinical impacts on mal-nourished mechanically ventilated critically ill patients who are dependent on TPN nutrition support. This study is limited by its single center, observational and retrospective design but our data may be useful in other larger, multisite and prospective study.

1. Alberda, C. et al. “The relationship between nutritional intake and clinical outcomes in critically ill patients: results of an international multicentre observational study.” Intensive Care Medicine, vol. 35, 2009, pp. 1728-1737.

2. Singer, P. et al. “The Tight Calorie Control Study (TICACOS): a prospective, randomized controlled pilot study of nutritional support in critically ill patients.” Intensive Care Medicine, vol. 37, 2011, pp. 601-609.

3. Barr, J. et al. “Outcomes in critically ill patients before and after the implementation of an evidence-based nutritional management protocol.” Chest, vol. 125, 2004, pp. 1446-1457.

4. McClave, S.A. et al. “Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).” Journal of Parenteral and Enteral Nutrition, vol. 40, 2016, pp. 159-211.

5. Marks, R.R. et al. “Acute kwashiorkor in the setting of cerebral palsy and pancreatic insufficiency.” Cutis, vol. 103, no. 1, January 2019, pp. E10-E12.

6. Puthucheary, Z.A. et al. “Acute skeletal muscle wasting in critical illness.” Journal of the American Medical Association, vol. 310, no. 15, 2013, pp. 1591-1600. https://doi.org/10.1001/jama.2013.278481.

7. Ochoa Gautier, J.B. et al. “How much and what type of protein should a critically ill patient receive?” Nutrition in Clinical Practice, vol. 32, no. 1 suppl., 2017, pp. 6S-14S. https://doi.org/10.1177/0884533617693609.

8. Heyland, D.K. et al. “Optimal amount of calories for critically ill patients: depends on how you slice the cake!” Critical Care Medicine, vol. 39, no. 12, 2011, pp. 2619-2626. https://doi.org/10.1097/CCM.0b013e318226641d.