Publications by authors named "W A C Koekkoek"

20 Publications

Micronutrient deficiencies in critical illness.

Clin Nutr 2021 Jun 11;40(6):3780-3786. Epub 2021 May 11.

Department of Intensive Care Medicine, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP, Ede, the Netherlands; Division of Human Nutrition and Health, Wageningen University & Research, HELIX (Building 124), Stippeneng 4, 6708 WE, Wageningen, the Netherlands. Electronic address:

Background & Aims: Low micronutrient levels in critical illness have been reported in multiple studies. Because of the antioxidant properties of various micronutrients, micronutrient deficiency may augment oxidative stress in critical illness. However, it remains unclear whether micronutrient concentrations in ICU patients are different from those in healthy age-matched controls. It is also unclear whether micronutrient deficiency develops, worsens, or resolves during ICU admission without supplementation.

Methods: We prospectively studied a cohort of adult critically ill patients. Micronutrient levels, including selenium, β-carotene, vitamin C, E, B and B were measured repeatedly during the first week of ICU admission. We compared the micronutrient concentrations at ICU admission to those of healthy age-matched controls. In addition, associations between micronutrient concentrations with severity of illness, inflammation and micronutrient intake were investigated.

Results: Micronutrient blood concentrations were obtained from 24 critically ill adults and 21 age-matched healthy controls. The mean micronutrient levels at admission in the ICU patients were: selenium 0.52 μmol/l, β-carotene 0.17 μmol/l, vitamin C 21.5 μmol/l, vitamin E 20.3 μmol/l, vitamin B 129.5 nmol/l and vitamin B 41.0 nmol/l. In the healthy controls micronutrient levels of selenium (0.90 μmol/l), β-carotene (0.50 μmol/l), vitamin C (45 μmol/l) and vitamin E (35.5 μmol/l) were significantly higher, while vitamin B (122 nmol/l) and B (44 nmol/l) were not significantly different between patients and controls. Selenium, vitamin B and vitamin B levels remained stable during ICU admission. Vitamin C levels dropped significantly until day 5 (p < 0.01). Vitamin E and β-carotene levels increased significantly on days 5-7 and day 7, respectively (p < 0.01). Micronutrient levels were not associated with severity of illness, CRP or micronutrient intake during the admission.

Conclusions: At admission, ICU patients already had lower plasma levels of selenium, β-carotene, vitamin C and vitamin E than healthy controls. Vitamin C levels dropped significantly during the first days of ICU admission, while β-carotene and vitamin E levels increased after 5-7 days. No association between micronutrient levels and severity of illness, C-reactive protein (CRP) or micronutrient intake was found. Progressive enteral tube feeding containing vitamins and trace elements does not normalize plasma levels in the first week of ICU stay. This was a hypothesis generating study and more investigation in a larger more diverse sample is needed.
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http://dx.doi.org/10.1016/j.clnu.2021.05.003DOI Listing
June 2021

Resting energy expenditure by indirect calorimetry versus the ventilator-VCO derived method in critically ill patients: The DREAM-VCO prospective comparative study.

Clin Nutr ESPEN 2020 10 31;39:137-143. Epub 2020 Jul 31.

Department of Intensive Care Medicine, Head of ICU & Research, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP, Ede, the Netherlands; Division of Human Nutrition and Health, Wageningen University & Research, HELIX (Building 124), Stippeneng 4, 6708 WE, Wageningen, the Netherlands. Electronic address:

Background & Aims: Both overfeeding and underfeeding of intensive care unit (ICU) patients are associated with worse outcomes. Predictive equations of nutritional requirements, though easily implemented, are highly inaccurate. Ideally, the individual caloric target is based on the frequent assessment of energy expenditure (EE). Indirect calorimetry is considered the gold standard but is not always available. EE estimated by ventilator-derived carbon dioxide consumption (EEVCO) has been proposed as an alternative to indirect calorimetry, but there is limited evidence to support the use of this method.

Methods: We prospectively studied a cohort of adult critically ill patients requiring mechanical ventilation and artificial nutrition. We aimed to compare the performance of the EEVCO with the EE measured by indirect calorimetry through the calculation of bias and precision (accuracy), agreement, reliability and 10% accuracy rates. The effect of including the food quotient (nutrition intake derived respiratory quotient) in contrast to a fixed respiratory quotient (0.86), into the EEVCO formula was also evaluated.

Results: In 31 mechanically ventilated patients, a total of 414 paired measurements were obtained. The mean estimated EEVCO was 2134 kcal/24 h, and the mean estimated EE by indirect calorimetry was 1623 kcal/24 h, depicting a significant bias of 511 kcal (95% CI 467-560, p < 0.001). The precision of EEVCO was low (lower and upper limit of agreement -63.1 kcal and 1087. o kcal), the reliability was good (intraclass correlation coefficient 0.613; 95% CI 0.550-0.669, p < 0.001) and the 10% accuracy rate was 7.0%. The food quotient was not significantly different from the respiratory quotient (0.870 vs. 0.878), with a small bias of 0.007 (95% CI 0.000-0.015, p = 0.54), low precision (lower and upper limit of agreement -0.16 and 0.13), poor reliability (intraclass correlation coefficient 0.148; 95% CI 0.053-0.240, p = 0.001) and a 10% accuracy rate of 77.5%. Estimated mean EEVCO, including the food quotient, was 2120 kcal/24 h, with a significant bias of 496 kcal (95% CI 451-542; p < 0.001) and low precision (lower and upper limit of agreement -157.6 kcal and 1170.3 kcal). The reliability with EE estimated by indirect calorimetry was good (intraclass correlation coefficient 0.610, 95% CI 0.550-0.661, p < 0.001), and the 10% accuracy rate was 9.2%.

Conclusions: EEVCO, compared with indirect calorimetry, overestimates actual energy expenditure. Although the reliability is acceptable, bias is significant, and the precision and accuracy rates are unacceptably low when the VCO method is used. Including the food quotient into the EEVCO equation does not improve its performance. Predictive equations, although inaccurate, may even predict energy expenditure better compared with the VCO-method. Indirect calorimetry remains the gold standard method.
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http://dx.doi.org/10.1016/j.clnesp.2020.07.005DOI Listing
October 2020

The effect of cisatracurium infusion on the energy expenditure of critically ill patients: an observational cohort study.

Crit Care 2020 Feb 3;24(1):32. Epub 2020 Feb 3.

Department of Intensive Care Medicine, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP, Ede, The Netherlands.

Background: Both overfeeding and underfeeding of intensive care unit (ICU) patients are associated with worse outcomes. A reliable estimation of the energy expenditure (EE) of ICU patients may help to avoid these phenomena. Several factors that influence EE have been studied previously. However, the effect of neuromuscular blocking agents on EE, which conceptually would lower EE, has not been extensively investigated.

Methods: We studied a cohort of adult critically ill patients requiring invasive mechanical ventilation and treatment with continuous infusion of cisatracurium for at least 12 h. The study aimed to quantify the effect of cisatracurium infusion on EE (primary endpoint). EE was estimated based on ventilator-derived VCO (EE in kcal/day = VCO × 8.19). A subgroup analysis of septic and non-septic patients was performed. Furthermore, the effects of body temperature and sepsis on EE were evaluated. A secondary endpoint was hypercaloric feeding (> 110% of EE) after cisatracurium infusion.

Results: In total, 122 patients were included. Mean EE before cisatracurium infusion was 1974 kcal/day and 1888 kcal/day after cisatracurium infusion. Multivariable analysis showed a significantly lower EE after cisatracurium infusion (MD - 132.0 kcal (95% CI - 212.0 to - 52.0; p = 0.001) in all patients. This difference was statistically significant in both sepsis and non-sepsis patients (p = 0.036 and p = 0.011). Non-sepsis patients had lower EE than sepsis patients (MD - 120.6 kcal; 95% CI - 200.5 to - 40.8, p = 0.003). Body temperature and EE were positively correlated (Spearman's rho = 0.486, p < 0.001). Hypercaloric feeding was observed in 7 patients.

Conclusions: Our data suggest that continuous infusion of cisatracurium in mechanically ventilated ICU patients is associated with a significant reduction in EE, although the magnitude of the effect is small. Sepsis and higher body temperature are associated with increased EE. Cisatracurium infusion is associated with overfeeding in only a minority of patients and therefore, in most patients, no reductions in caloric prescription are necessary.
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http://dx.doi.org/10.1186/s13054-020-2744-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998072PMC
February 2020

Association of PROtein and CAloric Intake and Clinical Outcomes in Adult SEPTic and Non-Septic ICU Patients on Prolonged Mechanical Ventilation: The PROCASEPT Retrospective Study.

JPEN J Parenter Enteral Nutr 2020 03 6;44(3):434-443. Epub 2019 Jun 6.

Department of Intensive Care Medicine, Gelderse Vallei Hospital, Ede, The Netherlands.

Background: The optimal nutritional support for critically ill septic patients remains unknown. This study evaluates the associations of macronutrient intake during the first week of intensive care unit (ICU) admission and long-term clinical outcomes in septic and non-septic patients.

Methods: Prolonged mechanically ventilated patients were retrospectively studied. The association of protein (low: <0.8 g/kg/d, medium: 0.8-1.2 g/kg/d, high >1.2 g/kg/d) and energy intake (<80%, 80%-110%, 110% of target) during days 1-3 and 4-7 after ICU admission and 6-month mortality was analyzed for septic and non-septic patients separately.

Results: A total of 423 patients were investigated. Of these, 297 had sepsis. In the sepsis group, medium protein intake at days 4-7 was associated with lower 6-month mortality (hazard ratio [HR]: 0.646, 95% confidence interval [CI]: 0.418-0.996, P=0.048) compared with high intake. In the non-sepsis group, early high and late low protein intake were associated with higher 6-month mortality (HR: 3.902, 95% CI: 1.505-10.115, P=0.005; HR: 2.642, 95% CI: 1.128-6.189, P=0.025) compared with low and high protein intake, respectively. For energy intake, late energy intake of >110% was associated with decreased mortality in septic patients (HR: 0.400, 95% CI: 0.222-0.721, P=0.002), whereas in non-septic patients, late medium energy intake (80%-110%) was associated with better survival (HR: 0.379, 95% CI: 0.175-0.820, P=0.014), both compared with low energy intake.

Conclusion: Divergent associations of macronutrient intake were found; early high protein intake in non-septic patients, but not in septic patients, was found to be associated with higher 6-month mortality.
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http://dx.doi.org/10.1002/jpen.1663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078979PMC
March 2020

Primum non nocere in early nutrition therapy during critical illness: Balancing the pros and cons of early very high protein administration.

Clin Nutr 2019 08 1;38(4):1963-1964. Epub 2019 May 1.

Head of ICU & Research, Department of Intensive Care Medicine, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP, Ede, the Netherlands. Electronic address:

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http://dx.doi.org/10.1016/j.clnu.2019.04.020DOI Listing
August 2019