The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in COVID-19 and Sepsis.

Zinc is a structural component of proteins, functions as a catalytic co-factor in DNA synthesis and transcription of hundreds of enzymes, and has a regulatory role in protein-DNA interactions of zinc-finger proteins. For many years, zinc has been acknowledged for its anti-oxidative and anti-inflammatory functions. Furthermore, zinc is a potent inhibitor of caspases-3, -7, and -8, modulating the caspase-controlled apoptosis and necroptosis. In recent years, the immunomodulatory role of zinc in sepsis and COVID-19 has been investigated. Both sepsis and COVID-19 are related to various regulated cell death (RCD) pathways, including apoptosis and necroptosis. Lack of zinc may have a negative effect on many immune functions, such as oxidative burst, cytokine production, chemotaxis, degranulation, phagocytosis, and RCD. While plasma zinc concentrations decline swiftly during both sepsis and COVID-19, this reduction is primarily attributed to a redistribution process associated with the inflammatory response. In this response, hepatic metallothionein production increases in reaction to cytokine release, which is linked to inflammation, and this protein effectively captures and stores zinc in the liver. Multiple regulatory mechanisms come into play, influencing the uptake of zinc, the binding of zinc to blood albumin and red blood cells, as well as the buffering and modulation of cytosolic zinc levels. Decreased zinc levels are associated with increasing severity of organ dysfunction, prolonged hospital stay and increased mortality in septic and COVID-19 patients. Results of recent studies focusing on these topics are summarized and discussed in this narrative review. Existing evidence currently does not support pharmacological zinc supplementation in patients with sepsis or COVID-19. Complementation and repletion should follow current guidelines for micronutrients in critically ill patients. Further research investigating the pharmacological mechanism of zinc in programmed cell death caused by invasive infections and its therapeutic potential in sepsis and COVID-19 could be worthwhile.

Ex Vivo Evaluation of Glutamine Treatment in Sepsis and Trauma in a Human Peripheral Blood Mononuclear Cells Model.

We aimed to assess the lipopolysaccharide (LPS), or heat shock (HS) induction, and glutamine-modulating effects on heat shock protein-90α (HSP90α) and cytokines in an ex vivo model using peripheral blood mononuclear cells (PBMCs). The PBMCs of patients with septic shock, trauma-related systemic inflammatory response syndrome (SIRS), and healthy subjects were incubated with 1 µg/mL LPS at 43 °C (HS). Glutamine 10 mM was added 1 hour before or after induction or not at all. We measured mRNA HSP90α, monocyte (m) and lymphocyte (l) HSP90α proteins, interleukin (IL)-1b, -6, -8, -10, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) supernatant levels. Heat shock increased the HSP90α mRNA and mHSP90α in all groups (10-fold in sepsis, p < 0.001 and p = 0.047, respectively). LPS induced the mHSP90α and lHSP90α in healthy (p < 0.001) and mHSP90α in SIRS (p = 0.004) but not in sepsis. LPS induced the cytokines at 24 and 48 h in all groups, especially in trauma (p < 0.001); HS only induced the IL-8 in healthy (p = 0.003) and septic subjects (p = 0.05). Glutamine at 10 mM before or after stimulation did not alter any induction effect of LPS or HS on HSP90α mRNA and mHSP90α protein in sepsis. In SIRS, glutamine before LPS decreased the mHSP90α but increased it when given after HS (p = 0.018). Before or after LPS (p = 0.049) and before HS (p = 0.018), glutamine decreased the lHSP90α expression in sepsis but increased it in SIRS when given after HS (p = 0.003). Regarding cytokines, glutamine enhanced the LPS-induced MCP-1 at 48 h in healthy (p = 0.011), SIRS (p < 0.001), and sepsis (p = 0.006). In conclusion, glutamine at 10 mM, before or after LPS and HS, modulates mHSP90α and lHSP90α in sepsis and SIRS differently and unpredictably. Although it does not alter the stimulation effect on interleukins, glutamine enhances the LPS induction effect on supernatant MCP-1 in all groups. Future research should seek to elucidate better the impact of glutamine and temperature modulation on HSP90α and MCP-1 pathways in sepsis and trauma.

External Validation of Equations to Estimate Resting Energy Expenditure in Critically Ill Children and Adolescents with and without Malnutrition: A Cross-Sectional Study.

We evaluated the validity of sixteen predictive energy expenditure equations for resting energy expenditure estimation (eREE) against measured resting energy expenditure using indirect calorimetry (REEIC) in 153 critically ill children. Predictive equations were included based on weight, height, sex, and age. The agreement between eREE and REEIC was analyzed using the Bland−Altman method. Precision was defined by the 95% limits of the agreement; differences > ±10% from REEIC were considered clinically unacceptable. The reliability was assessed by the intraclass correlation coefficient (Cronbach's alpha). The influence of anthropometric, nutritional, and clinical variables on REEIC was also assessed. Thirty (19.6%) of the 153 enrolled patients were malnourished (19.6%), and fifty-four were overweight (10.5%) or obese (24.8%). All patients received sedation and analgesia. Mortality was 3.9%. The calculated eREE either underestimated (median 606, IQR 512; 784 kcal/day) or overestimated (1126.6, 929; 1340 kcal/day) REEIC compared with indirect calorimetry (928.3, 651; 1239 kcal/day). These differences resulted in significant biases of −342 to 592 kcal (95% limits of agreement (precision)−1107 to 1380 kcal/day) and high coefficients of variation (up to 1242%). Although predicted equations exhibited moderate reliability, the clinically acceptable ±10% accuracy rate ranged from only 6.5% to a maximum of 24.2%, with the inaccuracy varying from −31% to +71.5% of the measured patient's energy needs. REEIC (p = 0.017) and eREE (p < 0.001) were higher in the underweight compared to overweight and obese patients. Apart from a younger age, malnutrition, clinical characteristics, temperature, vasoactive drugs, neuromuscular blockade, and energy intake did not affect REEIC and thereby predictive equations' accuracy. Commonly used predictive equations for calculating energy needs are inaccurate for individual patients, either underestimating or overestimating REEIC compared with indirect calorimetry. Altogether these findings underscore the urgency for measuring REEIC in clinical situations where accurate knowledge of energy needs is vital.

External Validation with Accuracy Confounders of VCO2-Derived Predicted Energy Expenditure Compared to Resting Energy Expenditure Measured by Indirect Calorimetry in Mechanically Ventilated Children.

Optimal energy provision, guided by measured resting energy expenditure (REE) and determined by indirect calorimetry (IC), is fundamental in Intensive Care Units (ICU). Because IC availability is limited, methods to predict REE based on carbon dioxide production (VCO2) measurements (REEVCO2) alone have been proposed as a surrogate for REE measured by IC (REEIC). The study aimed at externally and internally validating the accuracy of the REEVCO2 as an alternative to REEIC in mechanically ventilated children. A ventilator's integrated gas exchange module (E-COVX) was used to prospectively measure REEIC and predict REEVCO2 on 107 mechanically ventilated children during the first 24 h of admission. The accuracy of the REEVCO2 compared to REEIC was assessed through the calculation of bias and precision, paired median differences, linear regression, and ROC analysis. Accuracy within ±10% of the REEIC was deemed acceptable for the REEVCO2 equation. The calculated REEVCO2 based on respiratory quotient (RQ) 0.89 resulted in a mean bias of −72.7 kcal/day (95% limits of agreement −321.7 to 176.3 kcal/day) and a high coefficient of variation (174.7%), while 51.4% of the calculations fell outside the ±10% accuracy rate. REEVCO2 derived from RQ 0.80 or 0.85 did not improve accuracy. Only measured RQ (Beta 0.73, p < 0.001) and no-recorded neuromuscular blocking agents (Beta −0.13, p = 0.044) were independently associated with the REEVCO2−REEIC difference. Among the recorded anthropometric, metabolic, nutrition, or clinical variables, only measured RQ was a strong predictor of REEVCO2 inaccuracy (p < 0.001). Cutoffs of RQ = 0.80 predicted 89% of underestimated REEIC (sensitivity 0.99; specificity 0.89) and RQ = 0.82 predicted 56% of overestimated REEIC (sensitivity of 0.99; specificity 0.56). REEVCO2 cannot be recommended as an alternative to REEIC in mechanically ventilated children, regardless of the metabolic, anthropometric, or clinical status at the time of the evaluation.

Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations.

Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance is an independent sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with sepsis (n = 145), compared to non-infectious critically ill patients (n = 112) and healthy individuals (n = 89). Serum total oxidative status (TOS) and total antioxidant capacity (TAC) were measured by photometric testing. IL-6, -8, -10, -27, Hsp72/90 (ELISA), and selected antioxidant biomolecules (Ζn, glutathione) were correlated with apoptotic mediators (caspase-3, capsase-9) and the central anti-apoptotic survivin protein (ELISA, real-time PCR). A wide scattering of TOS, TAC, and TOS/TAC in all three groups was demonstrated. Septic patients had an elevated TOS/TAC, compared to non-infectious critically ill patients and healthy individuals (p = 0.001). TOS/TAC was associated with severity scores, procalcitonin, IL-6, -10, -27, IFN-γ, Hsp72, Hsp90, survivin protein, and survivin isoforms -2B, -ΔΕx3, -WT (p < 0.001). In a propensity probability (age-sex-adjusted) logistic regression model, only sepsis was independently associated with TOS/TAC (Exp(B) 25.4, p < 0.001). The AUCTOS/TAC (0.96 (95% CI = 0.93-0.99)) was higher than AUCTAC (z = 20, p < 0.001) or AUCTOS (z = 3.1, p = 0.002) in distinguishing sepsis. TOS/TAC, TOS, survivin isoforms -WT and -2B, Hsp90, IL-6, survivin protein, and repressed TAC were strong predictors of mortality (p < 0.01). Oxidant/antioxidant status is impaired in septic compared to critically ill patients with trauma or surgery and is related to anti-apoptotic, inflammatory, and innate immunity alterations. The unpredicted TOS/TAC imbalance might be related to undefined phenotypes in patients and healthy individuals.

Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis.

Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases' responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p < 0.05). Survivin correlated with IL-8 and caspase-9 (p < 0.01). For discriminating sepsis, caspase-9 achieved the best receiver operating characteristic curve (AUROC) of 0.95. In predicting mortality, caspase-9 and survivin protein achieved an AUROC of 0.70. In conclusion, specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in sepsis.

Increased glucocorticoid receptor expression in sepsis is related to heat shock proteins, cytokines, and cortisol and is associated with increased mortality.

BACKGROUND: The purposes of this study are to examine if the human glucocorticoid receptor (hGR) isoform-α mRNA and hGR protein expressions are deficient in the acute phase of sepsis (S) compared to systemic inflammatory response syndrome (SIRS) and healthy subjects (H) and to evaluate if the hGRα and hGR alterations are associated with cortisol changes and if they are related to (1) extracellular and intracellular heat shock proteins (HSP) 72 and 90α; (2) ACTH, prolactin, and interleukins (ILs); and (3) outcome. METHODS: Patients consecutively admitted to a university hospital intensive care unit (ICU) with S (n = 48) or SIRS (n = 40) were enrolled in the study. Thirty-five H were also included. Total mRNA was isolated from peripheral blood samples and cDNA was prepared. RT-PCR was performed. Intracellular hGR and HSP expression in monocytes and/or neutrophils was evaluated using four-colour flow cytometry. Serum prolactin, ACTH, and cortisol concentrations were also measured. ELISA was used to evaluate serum ILs and extracellular (e) HSPs (eHSP72, eHSP90α). RESULTS: hGR protein was higher in S compared to H and SIRS; hGRα mRNA was higher in S compared to H (p < 0.05). In sepsis, hGR protein and eHSP72 were higher among non-survivors compared to survivors (p < 0.05). The hGR MFI and hGRα mRNA fold changes were significantly related to each other (r s = 0.64, p < 0.001). Monocyte hGR protein expression was positively correlated with extracellular and intracellular HSPs, cortisol, and ILs and negatively to organ dysfunction (p < 0.05). HSPs, hGR, and cortisol were able to discriminate sepsis from SIRS (AUROC > 0.85, p < 0.05). In sepsis, monocyte-hGR protein and eHSP72 were strong predictors of mortality (AUROC > 0.95, p < 0.04). CONCLUSIONS: Acute-phase sepsis is associated with increased hGR expression and cortisol concentrations, possibly implying no need for exogenous steroids. At this stage, hGR is able to predict sepsis and outcome and is related to stress-activated bio-molecules and organ dysfunction.

Immunoparalysis: Clinical and immunological associations in SIRS and severe sepsis patients.

INTRODUCTION: This study was designed to identify changes in the monocytic membrane marker HLA-DR and heat shock proteins (HSPs) in relation to T-regulatory cells (T-regs) and other immunological marker changes in patients with systemic inflammatory response syndrome (SIRS) or sepsis/septic shock. METHODS: Healthy volunteers, intensive care unit (ICU) patients with SIRS due to head injury and ICU patients with severe sepsis/septic shock were enrolled in the current study. Determination of CD14+/HLA-DR+ cells, intracellular heat-shock proteins and other immunological parameters were performed by flow cytometry and RT-PCR techniques as appropriate. Univariate and multivariate analysis examined associations of CD14/HLA-DR, HSPs, T-regs and suppressor of cytokine signalling (SOCS) proteins with SIRS, sepsis and outcome. RESULTS: Fifty patients (37 with severe sepsis and 13 with SIRS) were enrolled, together with 20 healthy volunteers used as a control group. Compared to healthy individuals, patients with SIRS and severe sepsis showed progressive decline of their CD14/HLA-DR expression (0% to 7.7% to 50% within each study subpopulation, p<0.001). Mean fluorescent intensity (MFI) levels of HSP70 and HSP90 on monocytes and polymorphonuclear cells were significantly higher in SIRS patients compared to controls and fell significantly in severe sepsis/septic shock patients (p<0.05 for all comparisons). There was no statistically significant difference between subgroups for levels of T-regulatory cells or relative copies of Suppressor of Cytokine Signalling 3 (SOCS3) proteins. In univariate models percent of CD14/HLA-DR was associated with mortality (OR: 1.8 95%CI 1.02-3.2, p=0.05), while in multivariate models after adjusting for CD14/HLA-DR only younger age and lower Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were associated with increased chances of survival (beta -0.05, OR 0.9, 95% CI 0.9-0.99, p=0.038 for age and beta -0.11, OR 0.89, 95% CI 0.8-0.99, p=0.037 for APACHE II score). CONCLUSIONS: Significant associations with SIRS and sepsis were found for CD14/HLA-DR expression and monocyte and polymorphonuclear cell levels of HSP70 and 90. The role of these biomarkers in assessing the prognosis of sepsis needs to be further explored and validated in prospective studies.

Glutamine may repress the weak LPS and enhance the strong heat shock induction of monocyte and lymphocyte HSP72 proteins but may not modulate the HSP72 mRNA in patients with sepsis or trauma.

OBJECTIVE: We assessed the lipopolysaccharide (LPS) or heat shock (HS) induction of heat shock protein-72 (HSP72) in peripheral blood mononuclear cells (PBMCs) of patients with severe sepsis (SS) or trauma-related systemic inflammatory response syndrome (SIRS), compared to healthy individuals (H); we also investigated any pre- or posttreatment modulating glutamine (Gln) effect. METHODS: SS (11), SIRS (10), and H (19) PBMCs were incubated with 1 µg/mL LPS or 43°HS. Gln 10 mM was either added 1 h before or 1 h after induction or was not added at all. We measured monocyte (m), lymphocyte (l), mRNA HSP72, HSP72 polymorphisms, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and cortisol levels. RESULTS: Baseline lHSP72 was higher in SS (p < 0.03), and mHSP72 in SIRS (p < 0.02), compared to H. Only HS induced l/mHSP72/mRNA HSP72; LPS induced IL-6, IL-8, IL-10, and MCP-1. Induced mRNA was related to l/mHSP72, and was related negatively to cytokines. Intracellular l/mHSP72/HSP72 mRNA was related to serum ILs, not being influenced by cortisol, illness severity, and HSP72 polymorphisms. Gln did not induce mRNA in any group but modified l/mHSP72 after LPS/HS induction unpredictably. CONCLUSIONS: HSP72 mRNA and l/mHSP72 are higher among critically ill patients, further induced by HS, not by LPS. HSP72 proteins and HSP72 mRNA are related to serum ILs and are negatively related to supernatant cytokines, not being influenced by HSP72 polymorphisms, cortisol, or illness severity. Gln may depress l/mHSP72 after LPS exposure and enhance them after HS induction, but it may not affect early induced HSP72 mRNA.

Glutamine suppresses Hsp72 not Hsp90α and is not inducing Th1, Th2, or Th17 cytokine responses in human septic PBMCs.

OBJECTIVE: L-Alanyl-glutamine (L-Ala-Gln) is a pharmaco-nutrient commonly used in nutrition regimens due to its immunomodulatory effects. In critically ill patients who are septic, L-Ala-Gln was associated with an increase in mortality. The aim of this study was to investigate whether L-Ala-Gln modulated heat shock protein (Hsp)-72, 90-α, T helper (Th)1, Th2, and Th17 cytokine expression in the peripheral blood mononuclear cells (PBMC) of patients with severe sepsis. METHODS: Time-dose effects of L-Ala-Gln were compared with those of L-glutamine (L-Gln) and lipopolysaccharide (LPS) and to healthy controls. PBMCs were incubated with 1 or 10 µg/mL LPS, 5 or 10 mM L-Gln, and 5 or 10 mM L-Ala-Gln for different periods of time (0; 4; 24 h) when culture supernatants were harvested. RESULTS: In both groups, basal Hsp72 increased over time (P < 0.02); Hsp90-α levels declined in controls (P < 0.02) but remained increased in septic patients (P < 0.02), not exhibiting any significant time-response trend. Both Glns suppressed Hsp72 in septic and controls at 10 mM by 4 h (P < 0.045) and Hsp90-α in the control group by 24 h (P < 0.045). LPS did not induce Hsps in either group. L-Ala-Gln did not induce any of the Th1, Th2, and Th17 cytokines in either group. CONCLUSION: High doses of L-Gln or L-Ala-Gln do not induce any of the Th1, Th2, and Th17 cytokines in either healthy or septic human PBMCs. High Gln doses suppress Hsp72 in septic and control PBMCs. Hsp90-α time-series expression declines, contrasting the increasing trend of Hsp72 in healthy controls. Hsp90-α sustains increased levels in septic supernatants, showing a characteristic longitudinal behavior needed further elucidation.

Heat shock protein 72 expressing stress in sepsis: unbridgeable gap between animal and human studies--a hypothetical "comparative" study.

Heat shock protein 72 (Hsp72) exhibits a protective role during times of increased risk of pathogenic challenge and/or tissue damage. The aim of the study was to ascertain Hsp72 protective effect differences between animal and human studies in sepsis using a hypothetical "comparative study" model. Forty-one in vivo (56.1%), in vitro (17.1%), or combined (26.8%) animal and 14 in vivo (2) or in vitro (12) human Hsp72 studies (P < 0.0001) were enrolled in the analysis. Of the 14 human studies, 50% showed a protective Hsp72 effect compared to 95.8% protection shown in septic animal studies (P < 0.0001). Only human studies reported Hsp72-associated mortality (21.4%) or infection (7.1%) or reported results (14.3%) to be nonprotective (P < 0.001). In animal models, any Hsp72 induction method tried increased intracellular Hsp72 (100%), compared to 57.1% of human studies (P < 0.02), reduced proinflammatory cytokines (28/29), and enhanced survival (18/18). Animal studies show a clear Hsp72 protective effect in sepsis. Human studies are inconclusive, showing either protection or a possible relation to mortality and infections. This might be due to the fact that using evermore purified target cell populations in animal models, a lot of clinical information regarding the net response that occurs in sepsis is missing.

Glutamine randomized studies in early life: the unsolved riddle of experimental and clinical studies.

Glutamine may have benefits during immaturity or critical illness in early life but its effects on outcome end hardpoints are controversial. Our aim was to review randomized studies on glutamine supplementation in pups, infants, and children examining whether glutamine affects outcome. Experimental work has proposed various mechanisms of glutamine action but none of the randomized studies in early life showed any effect on mortality and only a few showed some effect on inflammatory response, organ function, and a trend for infection control. Although apparently safe in animal models (pups), premature infants, and critically ill children, glutamine supplementation does not reduce mortality or late onset sepsis, and its routine use cannot be recommended in these sensitive populations. Large prospectively stratified trials are needed to better define the crucial interrelations of "glutamine-heat shock proteins-stress response" in critical illness and to identify the specific subgroups of premature neonates and critically ill infants or children who may have a greater need for glutamine and who may eventually benefit from its supplementation. The methodological problems noted in the reviewed randomized experimental and clinical trials should be seriously considered in any future well-designed large blinded randomized controlled trial involving glutamine supplementation in critical illness.

Educational polymorphisms of basic life support algorithms.

BACKGROUND: A systematic review of the pooled effect of articles presenting current basic life support (BLS) algorithms for the treatment of cardiac arrest has never been carried. AIMS: We aimed to record and classify potential inherent factors influencing simplicity negatively in teaching, learning and retention of cardiopulmonary resuscitation (CPR) delivered by health care providers or lay persons. METHODS: We performed a search of the relevant literature exploring MEDLINE, COCHRANE LIBRARY and SCOPUS databases. Potential inhibitory factors in the structure of available algorithms influencing simplicity in teaching, learning and retention of BLS were recorded and stratified accordingly. In a second phase of this study, we tested the hypothesis that different options of a BLS algorithm might influence CPR retention negatively, by asking 348 health care provider participants of our CPR seminars to describe their predicted response in an emergency to: (1) a real-time model implicating the various victims and rescuers; and (2) a hypothetical challenging 'all-in-one' BLS algorithm model. RESULTS: Fifteen articles presenting current BLS algorithms evidenced 163 suggestions that produced 23 different CPR options: five contrasting algorithms (21.8%); three two-option models (13%); six vague technical or scientific suggestions (26%); and nine multiple choices of action (39.1%). Identified references contributed differently in the development of educationally polymorphic BLS options in each of the four categories (P < 0.0001) and were all brought about by variants of victims and rescuers. Participants of CPR seminars answered that in an emergency they could remember the hypothetical BLS model (90%, P = 0.007) rather than a current BLS algorithm for adults (42.2%) or children (36%). CONCLUSIONS: Educational polymorphisms of BLS algorithms could build unpredictable barriers between rescuers and cardiac arrest victims and might seriously limit instructors' educational effectiveness. These findings might support an alternative trial hypothesis of a simple 'all-in-one algorithm' educational approach in future.

The effects of endotracheal suctioning on the accuracy of oxygen consumption and carbon dioxide production measurements and pulmonary mechanics calculated by a compact metabolic monitor.

BACKGROUND: Open endotracheal suctioning (ETS), which is performed regularly in mechanically ventilated patients to remove obstructive secretions, can cause an immediate decrease in dynamic compliance and expired tidal volume and result in inadequate or inaccurate sidestream respiratory monitoring, necessitating prolonged periods of stabilization of connected metabolic monitors. We investigated the immediate effect of open ETS on the accuracy of oxygen consumption (VO2) and carbon dioxide production (VCO2) measurements and calculated lung mechanics, respiratory quotient, and resting energy expenditure in mechanically ventilated children without severe lung pathology, when using a compact modular metabolic monitor (E-COVX) continuously recording patient spirometry and gas exchange measurements. METHODS: Open ETS was performed when clinically indicated in 11 children mechanically ventilated for sepsis or head injury. A total of 2800 pulmonary 1-min gas exchange measurements were recorded in 28 ETS instances for 50 consecutive minutes before and 50 min after the standardized procedure. RESULTS: Pulmonary mechanics and indirect calorimetry did not differ between pre- and postsuction sets of measurements. Pre- and postsuction VO2, VCO2, dynamic airway resistance, dynamic compliance, and expiratory minute ventilation remained stable from 5 to 55 min after tracheal suctioning and did not differ among different ventilatory modes. Average paired differences of sequential pre- and postsuction VO2, VCO2, respiratory quotient, and resting energy expenditure were -0.6%, -1%, -0.1%, and -0.3%. Ratio differences between the first and the second periods of measurements (1-25 vs 26-50 sets of 1-min measurements) did not differ in the two groups. CONCLUSIONS: Pulmonary mechanics and indirect calorimetry measurements are not influenced after uneventful open ETS in well-sedated patients. The E-COVX is able to reliably record spirometry and metabolic indices as early as 5 min after suctioning at different ventilator modes.

Influence of different ventilator modes on Vo(2) and Vco(2) measurements using a compact metabolic monitor.

OBJECTIVE: We assessed the influence of different ventilator modes on carbon dioxide elimination (Vco(2)) and oxygen uptake (Vo(2)) using a new compact modular metabolic monitor (E-COVX) and its impact on calculated respiratory quotient (RQ) and resting energy expenditure (REE) in critically ill children. METHODS: Sequential 30-min ventilation by pressure-regulated volume controlled ventilation (PRVC), synchronized intermittent mandatory ventilation (SIMV), and biphasic intermittent positive airway pressure/airway pressure release ventilation (BiVent) in mechanically ventilated critically-ill children was assessed. To determine within- or between-day variations, 30-min Vo(2) and Vco(2) measurements were repeated at four separate occasions. RESULTS: A total of 3960pulmonary 1-min gas exchange measurements were recorded in the 44 sessions for the three ventilator modes. Vo(2), Vco(2), and REE did not differ significantly among the PRVC, SIMV, and BiVent sequence of measurements. RQ (0.86+/-0.1) in the SIMV and Vco(2) (113+/-55mL/min) in the BiVent mode had a higher trend compared with PRVC (0.82+/-0.01, P<0.05, and 103+/-49mL/min, P<0.2, respectively). All three modes displayed good agreement and there were no significant differences between the first and second same-day or between the first- and second-day measurements or sequentially changed ventilator modes. Bland-Altman plots comparing the means of sequential REE, Vo(2), Vco(2), and RQ during the PRVC, SIMV, and BiVent modes of ventilation indicated that the average paired differences were <-5.5%. CONCLUSION: The influence of different ventilator modes on Vo(2) and Vco(2) measurements in adequately sedated critically ill children is not significant. The E-COVX metabolic module is suitable for repeated measurements in well-sedated mechanically ventilated children with stable respiratory patterns using the PRVC, SIMV, or BiVent modes of ventilation.