INTRODUCTION:Pregnancy is a hypercoagulable state that raises the risk of venous thromboembolism VTE), particularly in women with thrombophilia. D-Dimer levels increase during the activation of the coagulation cascade and are used to exclude VTE in non-pregnant women. This study aimed to analyze the influence of thrombophilia and the use of low molecular weight heparin (LMWH) on D-dimer levels in pregnant women. METHODS:We retrospectively analyzed data from pregnant women presenting at the hemostaseology outpatient clinic of the University Hospital of Leipzig between July 2016 and June 2023. The women were seen at intervals of four to six weeks and D-dimer concentrations were measured at every visit. RESULTS:A total of 301 women were included in the study, of whom 121 were diagnosed with thrombophilia. The concentration of D-dimer increased continuously throughout pregnancy both in women with and without LMWH. Patients diagnosed with thrombophilia had similar D-Dimer levels compared to women without thrombophilia, irrespective of LMWH administration. Women with heterozygous Factor-V-Leiden mutation who did not receive thromboprophylaxis had higher D-Dimer levels during most of their pregnancy than those without thrombophilia. The initiation of LMWH led to a significant reduction of D-dimers in early pregnancy, and patients started on LMWH prophylaxis early in pregnancy had lower D-dimers later in pregnancy. CONCLUSION:This is one of the largest studies evaluating D-dimer concentrations in women with high-risk pregnancies. Further studies with clinical endpoints are required to evaluate the role of D-dimers in deciding whether to initiate LMWH prophylaxis.
BACKGROUND:Intravenous drug administration is essential in intensive care treatment. However, the risk of particulate contamination in infusion solutions during treatment is often underestimated. METHODS:Residual amounts of infusion solutions prepared and administered at the adult intensive care unit were examined for visible and subvisible particles according to the recommendations of the European Pharmacopoeia monographs 2.9.19 and 2.9.20. RESULTS:Samples from 169 infusion solutions were collected, 149 of which could be analysed. The Pharmacopoeia requirements for visible particles were not fulfilled in 42.9% (n=64/149) of the samples, while the requirements for subvisible particles were not met in 4.7% (n=7/149). A specific correlation between the pharmaceutical drugs or within the infusion set (bottle vs connected infusion line) and particulate contamination was not possible as the sample was too small for a correlation analysis. A Spearman rho analysis showed no correlation between particle contamination and administration mode (subvisible (10 µm): p=0.969, r=-0.005; subvisible (25 µm): p=0.834, r=-0.026; visible: p=0.711, r=-0.047) and particle contamination and dosage form (subvisible (10 µm): p=0.291, r=-0.092; subvisible (25 µm): p=0.513, r=0.057; visible: p=0.415, r=0.071). CONCLUSIONS:This study showed that residuals of intravenously administered solutions have particulate contaminations. A specific causal factor was not identified.
Nutritional therapy is a key component of critical care management, yet optimal strategies remain debated due to the heterogeneity of ICU patients, dynamic metabolic alterations, and the profound influence of inflammation on nutrient utilisation. Evidence from recent trials has challenged traditional one-size-fits-all approaches, emphasising the need for individualised, phase-specific nutrition throughout the continuum of critical illness and recovery. This manuscript summarises current concepts and emerging evidence in nutrition therapy presented at the 39th Annual Conference of the German Society for Nutritional Medicine (DGEM). Experts reviewed and critically discussed inflammation-driven metabolic changes, personalised energy and protein prescriptions, micronutrient management, macronutrient adaptation, ketogenic strategies in neurocritical care and sepsis, and nutritional considerations in post-ICU syndrome and outpatient recovery. This overview does not claim to be exhaustive; interpretations of individual study results partly reflect the views of the experts. Together with the inclusion of newer therapeutic approaches, this is intended to stimulate discussion and, at the same time, provide a basis for further studies. Inflammation and high disease severity strongly influence nutritional responsiveness, with highly inflamed patients demonstrating reduced benefit and heightened risk of overfeeding. Personalised strategies, including indirect calorimetry, fat-free mass–based protein dosing, and metabolic biomarkers such as the urea-creatinine ratio, offer a rational framework for tailoring therapy. Micronutrient deficiencies are common due to redistribution, pre-existing deficits, and extracorporeal losses, necessitating structured assessment and supplementation. Macronutrient delivery should be progressively escalated and regarded as a pharmacologic intervention aligned with disease phase and organ function. Early standardised ketogenic diet protocols show feasibility and potential clinical benefit in refractory status epilepticus and sepsis. Post-ICU and outpatient phases remain nutritionally vulnerable, with persistent catabolism and underfeeding common; structured, multidisciplinary rehabilitation and transitional nutrition programs may improve long-term outcomes. Future personalised nutrition strategies may rely on metabolic phenotyping and biomarker-informed stratification rather than uniform protein, energy and micronutrient targets for all ICU patients. Integrating individualised energy and protein prescription, targeted micronutrient management, emerging metabolic therapies, and coordinated post-ICU rehabilitation may optimise recovery and functional outcomes. Robust clinical trials are needed to confirm the impact of these personalised strategies on long-term patient-centred endpoints.
Background: Prothrombin gene mutations can be associated with either a thrombotic or a bleeding risk. Genomic studies and coagulation workup can provide valuable information to better understand their clinical importance. Key Clinical Question: We describe the case of a woman with a duplication of the entire prothrombin gene. Clinical Approach: A 42-year-old woman presented for thrombophilia screening following a history of unprovoked arterial and superficial venous thrombotic episodes. Coagulation workup demonstrated a marked increase in prothrombin levels and ex vivo thrombin generation. Genetic analysis revealed a duplication of at least 307.9 kb (maximum 366.7 kb): arr[ChRCh38]:11p11.2(46,455,533-46,763,446)x3, encompassing the entire prothrombin gene and 6 adjacent protein-coding genes (HARBI1, ATG13, ARHGAP1, and ZNF408 completely involved, and AMBRA1 and CKAP5 partially involved). Conclusion: The present case demonstrated duplication of the entire prothrombin gene, associated with a significant hypercoagulable risk, a finding not previously reported in the literature.
Importance:Albumin supplementation may reduce mortality in patients with septic shock; however, data from randomized clinical trials are limited. Objective:To assess the impact of albumin administration on outcomes in patients with septic shock. Design, Setting, and Participants:This multicenter, open-label randomized clinical trial was conducted between October 21, 2019, and May 2, 2022. Patients from 23 intensive care units in Germany enrolled within 24 hours of the onset of septic shock were followed up for outcome data up to 90 days. The statistical trial report was completed and filed with the federal authorities in December 2023; additional analyses were completed in October 2024. The study was terminated prematurely due to low enrollment rates. Interventions:Protocol group patients received 20% albumin to maintain serum albumin levels of at least 3.0 g/dL for up to 28 days during their intensive care unit admission. The control group received standard fluid administration with crystalloids. Main Outcomes and Measures:The primary end point was 90-day mortality; secondary end points included 28-day, 60-day, intensive care unit and in-hospital mortality, organ dysfunction or failure, total amount of fluid administration and total fluid balance while in the intensive care unit, duration of intensive care and hospital stays, and frequency of adverse events. Results:Of 440 randomized patients (median [IQR] age, 69 [59-78] years; 290 [65.9%] male), 222 received albumin and 218 received standard fluids. Baseline characteristics were comparable. Ninety-day mortality was 43.3% (91 of 210) in the albumin group vs 45.9% (96 of 209) in controls (relative risk, 0.94; 95% CI, 0.76-1.17; P = .71). No significant differences were observed for secondary end points. Conclusions and Relevance:In this randomized clinical trial of patients with septic shock, albumin administration was safe but did not improve 90-day survival. As this trial was prematurely terminated, results remain inconclusive and additional studies are recommended. Trial Registration:ClinicalTrials.gov Identifier: NCT03869385.
QuestionCan the reported potential mortality reduction by albumin replacement in septic shock be confirmed in a randomized clinical trial?FindingsIn a multicenter randomized clinical trial, 440 adults with septic shock were treated with albumin therapy aiming to maintain serum albumin concentrations greater than 3.0 g/dL or with standard fluid therapy. Ninety-day mortality did not differ significantly between the albumin group (43.3%) and the controls (45.9%).MeaningThese results suggest that albumin administration was safe but did not improve 90-day survival in patients with septic shock; results remain inconclusive due to premature trial termination. This randomized clinical trial of patients with septic shock assesses whether albumin reduces 90-day mortality. ImportanceAlbumin supplementation may reduce mortality in patients with septic shock; however, data from randomized clinical trials are limited.ObjectiveTo assess the impact of albumin administration on outcomes in patients with septic shock.Design, Setting, and ParticipantsThis multicenter, open-label randomized clinical trial was conducted between October 21, 2019, and May 2, 2022. Patients from 23 intensive care units in Germany enrolled within 24 hours of the onset of septic shock were followed up for outcome data up to 90 days. The statistical trial report was completed and filed with the federal authorities in December 2023; additional analyses were completed in October 2024. The study was terminated prematurely due to low enrollment rates.InterventionsProtocol group patients received 20% albumin to maintain serum albumin levels of at least 3.0 g/dL for up to 28 days during their intensive care unit admission. The control group received standard fluid administration with crystalloids.Main Outcomes and MeasuresThe primary end point was 90-day mortality; secondary end points included 28-day, 60-day, intensive care unit and in-hospital mortality, organ dysfunction or failure, total amount of fluid administration and total fluid balance while in the intensive care unit, duration of intensive care and hospital stays, and frequency of adverse events.ResultsOf 440 randomized patients (median [IQR] age, 69 [59-78] years; 290 [65.9%] male), 222 received albumin and 218 received standard fluids. Baseline characteristics were comparable. Ninety-day mortality was 43.3% (91 of 210) in the albumin group vs 45.9% (96 of 209) in controls (relative risk, 0.94; 95% CI, 0.76-1.17; P = .71). No significant differences were observed for secondary end points.Conclusions and RelevanceIn this randomized clinical trial of patients with septic shock, albumin administration was safe but did not improve 90-day survival. As this trial was prematurely terminated, results remain inconclusive and additional studies are recommended.Trial RegistrationClinicalTrials.gov Identifier: NCT03869385
ABSTRACT:Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening condition. Caplacizumab substantially shortens the time to clinical response, yet delayed platelet count recovery is occasionally observed, raising concerns about iTTP refractoriness. This retrospective multicenter study analyzed 204 acute iTTP episodes reported to the German REACT (Retrospective Evaluation of Acquired Thrombotic Thrombocytopenic Purpura in Caplacizumab-Treated Patients) 2020 and ATMAR (Austrian Thrombotic Microangiopathy Registry) registries, all treated with caplacizumab. Refractoriness was assessed using the 2017 International Working Group criteria and the more stringent definition by the French Reference Center for Thrombotic Microangiopathies. We evaluated time to platelet recovery and presence of confounding clinical conditions, potentially accounting for persistent thrombocytopenia, in all episodes. By day 5 after caplacizumab initiation, 171 of 204 patients (83.8%) achieved a clinical response, and the remaining 33 of 204 (16.2%) showed at least a doubling of the platelet count. Only 3 patients (1.5%) met laboratory criteria for refractoriness. In all cases, plausible alternative causes were present (eg, missed doses, infection). No patient was refractory without a confounding factor. In 8 of 204 patients (3.9%) we observed a markedly prolonged thrombocytopenia (≥10 days) and identified confounding conditions in all cases. In the stratified Cox model, the presence of alternative causes of thrombocytopenia was the only independent determinant of delayed platelet count normalization (hazard ratio, 0.16; 95% confidence interval, 0.09-0.28; P< .001). In the context of caplacizumab-based therapy, true refractoriness is rare. Delayed platelet count recovery is predominantly attributable to concomitant clinical conditions. Careful clinical assessment and context-sensitive interpretation of treatment response before escalating iTTP-specific therapy may avoid unnecessary treatment intensification and associated risks.
Background: Light transmission aggregometry (LTA) plays an important role in the detection of platelet function disorders. Objectives: This study compared different agonist concentrations to detect patients with bleeding disorder of unknown cause (BDUC) with healthy blood donors. Methods: We retrospectively evaluated LTA performed in patients with BDUC and compared the results with prospectively collected LTA measurements from healthy blood donors. LTA was assessed with 2 μM, 5 μM, and 20 μM adenine diphosphate (ADP) in both groups; 1.0 mM arachidonic acid (AA) and 5 μM epinephrine in persons with BDUC; 1.0 mM and 1.5 mM AA and 5 μM and 10μM epinephrine in healthy blood donors. Results: After induction with 2 μM ADP, 43.8% of persons with BDUC and 24.3% of the healthy blood donors had abnormal maximum aggregation, but only 5.8% and 4.6% after induction with 5 μM ADP, respectively. Persons with BDUC had a higher proportion of abnormal maximum aggregation after induction with 1 mM AA (18.5%) compared to healthy donors (3.6%). No difference was observed after epinephrine induction. The sensitivity of an abnormal International Society on Thrombosis and Haemostasis Bleeding Assessment Tool score to predict an abnormal LTA was <22% and the negative predictive value >70%. Conclusion: This study reveals a high proportion of abnormal LTA results in persons with BDUC and healthy blood donors after induction with low concentrations of ADP and AA. The recommendations for those concentrations in guidelines for platelet function testing should be reassessed.
Patients with hematologic malignancies often require platelet transfusions, but platelet count alone does not sufficiently predict bleeding risk. T-TAS HD-Chip is designed to evaluate the hemostatic function in whole blood samples from thrombocytopenic patients. This study aimed to investigate T-TAS HD-chip in thrombocytopenic patients with myeloid neoplasia. Samples from thrombocytopenic patients with myeloid neoplasia were prospectively collected. The area under the curve (AUC), occlusion start time and occlusion time of T-TAS, platelet count, von Willebrand factor and thrombin generation were measured, and the association of these markers with platelet transfusion, parenteral nutrition and bleeding events was evaluated. A total of 67 samples were collected from 28 patients. No occlusion in T-TAS was detected in samples with platelet counts ≤20 × 109 per liter but 17 of 35 samples with platelet counts > 20 × 109 per liter showed occlusion, p < 0.001. In samples from patients with platelet counts > 20 × 109 per liter, 26.3
Many commensal bacteria that peacefully reside in the human microbiome are also able to cause acute opportunistic infections. Emerging evidence suggests that within-host evolution contributes to infection, but the genetic mechanisms facilitating the progression of opportunistic pathogens from carriage to acute infections is unknown. Here, we prospectively collected native samples from four microbiome niches of 13 critically ill patients, among whom we have observed eleven hospital-associated infections (HAI). Leveraging a culture-based approach, we demonstrate that the microbiome is frequently (73%) colonized by the pathogenic lineage already before or at the time of diagnosis. Moreover, we identify a short-lived, non-synonymous mutation within the fimbriae regulator gene fimZ (F126L) of Enterobacter hormaechei , first detectable within the gut and subsequently associated with HAI before becoming replaced by body-wide sweeps of independent treatment-associated mutations. Despite fimZ [F126L] being globally undetected, we can show in vitro and in vivo that the F126L mutation leads to elevated biofilm formation, cell adhesion and virulence, suggesting a role during HAI. Our work highlights the power of prospective, population-wide investigation of pathogens to elucidate rapid evolution linked to disease. ### Competing Interest Statement The authors have declared no competing interest. Max Planck Society, https://ror.org/01hhn8329
Beim Management des Herz-Kreislauf-Stillstands („out-of-hospital cardiac arrest“ [OHCA]) ist eine zügige Risikostratifizierung bezüglich Deeskalation oder Eskalation der Therapie wichtig. Wir identifizierten und verglichen Prognosescores für Rettungsdienst und Notaufnahme zur Vorhersage des 30-Tages-Überlebens mit gutem neurologischem Ergebnis (Cerebral Performance Score [CPC] 1 oder 2) nach nichttraumatisch bedingtem OHCA. Neben dem CRASS-Score identifizierten wir SWAP, GRApH und ein 4‑Schritt-Modell durch Literaturrecherche. Die Scores wurden bei 570 erwachsenen Patient*innen, welche zwischen 01/2018 und 05/2023 nach OHCA in unserem Klinikum aufgenommen wurden, angewendet. Wir verglichen die Fläche unter der Receiver-operator-Kurve (AUROC), Testgütekriterien und Kalibration. Das 30-Tages-Überleben mit CPC 1/2 war 15,4
The evidence for the administration of blood products in the critically ill is frequently meagre. It is often difficult to differentiate between adaptive changes and pathological alterations of blood components requiring treatment. Anemia is frequently observed in critically ill patients; however, there is no evidence for a benefit of a liberal transfusion strategy. Thrombocytopenia and alterations in plasmatic coagulation could correlate with an unfavorable outcome but they are not predictive regarding a substitution. Therefore, the indications for platelet transfusion and the administration of plasma or coagulation factor concentrates should always be clinically and critically evaluated. There is also no evidence for the generous use of albumin in intensive care medicine. In conclusion, a restrictive strategy is recommended for all blood products. The available evidence and a critical clinical assessment should be the mainstays of the decision for treatment with blood products.
OBJECTIVES:Despite limited sensitivity and specificity, blood cultures (BCs) still represent the gold standard of diagnostic care in septic patients. We aimed to overcome current diagnostic limitations by unbiased next-generation sequencing (NGS) of circulating microbial cell-free DNA (mcfDNA) in plasma samples. METHODS:We performed a prospective, observational, non-interventional, multicenter study (Next GeneSiS-Trial) to compare positivity rates for NGS-based identification of causative pathogens with BCs in patients suffering from sepsis or septic shock. An independent expert panel (n=3) retrospectively evaluated the plausibility of NGS-based findings and the potential for anti-infective treatment adaptations based on NGS results. RESULTS:The positivity rate of NGS-based diagnostics (NGS+) for 491 septic patients was 70.5% compared to positive BCs (BC+) with 19.4% within the first three days after sepsis onset. NGS+ results were evaluated as plausible in 98.6% of cases by the expert panel. Based on the experts´ recommendations, additional knowledge of NGS-based pathogen findings would have resulted in anti-infective treatment adaptations in 32.6% of all patients. Potentially inadequately treated NGS+/blood culture negative (BC-) patients showed worse outcomes. CONCLUSION:The integration of NGS-based pathogen diagnostics in sepsis has the potential to improve patients´ outcomes as compared to a treatment strategy based on standard-of-care microbiological diagnostics alone.
Die Evidenz für den Einsatz von Blutprodukten bei kritisch Kranken ist meist unzureichend. Die Unterscheidung zwischen adaptiven und therapiebedürftig pathologischen Veränderungen der Blutbestandteile ist oft schwierig. Eine Anämie kommt bei kritisch Kranken häufig vor. Es gibt jedoch keinen Beweis für den Vorteil einer liberalen Transfusionsstrategie. Thrombozytopenie und Veränderungen der plasmatischen Gerinnung können mit einer ungünstigen Prognose korrelieren, jedoch erlauben sie keine Aussage hinsichtlich einer Substitution. Die Thrombozytentransfusion und die Gabe von Plasma oder Gerinnungsfaktorenkonzentraten sollten daher stets klinisch und kritisch evaluiert werden. Auch für einen großzügigen Einsatz von Humanalbumin in der Intensivmedizin fehlt meist die Evidenz. Zusammenfassend wird eine restriktive Strategie bei allen Blutprodukten empfohlen. Verfügbare Evidenz und kritische klinische Einschätzung sollten bei der Entscheidung zur Therapie mit Blutprodukten im Vordergrund stehen.
Kidney replacement therapy (KRT) is frequently implemented in the intensive care unit. While measuring energy expenditure is recommended in the critically ill, the influence of KRT on indirect calorimetry (IC) is not fully clear. This prospective study aimed to investigate the influence of continuous veno-venous hemodialysis (CVVHD) and slow extended daily dialysis (SLEDD) on IC variables. We included critically ill mechanically ventilated adult medical patients on KRT for acute kidney injury. CVVHD was run with regional citrate anticoagulation, while SLEDD with systemic heparin anticoagulation. We conducted IC twice on every patient, either immediately before the planned termination of KRT and then an hour after the end of KRT or immediately before commencement of KRT and then again after an hour on KRT. We included 100 patients (75 males) with a median age of 64.0 years, a mean APACHE-II score of 30.9 and a mean SOFA score of 11.3 on the day of IC. There was no significant difference in median resting energy expenditure with versus without CVVHD (8029 [6993–9644] versus 7814 [6962–9304] kJ, p = 0.75) as well as with versus without SLEDD (9258 [8017–10,364] versus 9269 [8070–11,065] kJ, p = 0.63). The difference in resting energy expenditure between the two measurements was also not significant regardless of the sequence of IC measurements (p = 0.69). This prospective study on critically ill adult patients did not show any significant difference for indirect calorimetry variables between measurements conducted during CVVHD and SLEDD compared to those without KRT. ClinicalTrials.gov ID: NCT04599569
Background and aims:Acute on chronic liver failure (ACLF) represents the most severe outcome of acute decompensation in patients with liver cirrhosis, with ACLF-grade 3 carrying a nearly 80% mortality rate within 28 days. Prognosis is especially dire within the first 3-7 days with full organ support. Currently, effective treatments are limited to transplantation, but therapeutic plasma exchange (TPE) may contribute by removing harmful inflammatory mediators and replenishing essential proteins, thus offering promise for patients unresponsive to standard medical treatments (SMT). Material and methods:This retrospective study analyzed patients with ACLF receiving SMT with or without TPE at a tertiary care transplant center. Patients were monitored for at least 90 days postdiagnosis. The primary endpoint was 28-day transplant-free survival, with secondary endpoints including 90-day transplant-free survival, organ dysfunction parameters, and chronic liver failure consortium (CLIF-C) scores. A cohort of 25 patients treated with SMT + TPE and 65 with SMT alone was identified. Propensity scores enabled 1:1 matching, resulting in a final analysis of 40 patients (20 TPE group and 20 SMT group). Results:Patients underwent a median of three (IQR 2.25-5) TPE sessions, starting a median of 14 (IQR 7.25-17) days after ACLF diagnosis. Significant improvements were observed in ACLF grade, CLIF-C-ACLF score, hepatic encephalopathy and prothrombin time 24-48 h postfinal TPE session. The 28-day transplant-free survival rates were 70% in the TPE group versus 45% in the SMT group (P = 0.083) and at 90 days, survival rates were 30% in bothgroups (P = 0.426). Patients unresponsive to SMT who received TPE had significantly higher 28-day transplant-free survival rates compared to those treated with SMT alone (70.6% vs 26.7%, P = 0.008). Conclusion:TPE may demonstrate potential efficacy in ameliorating organ dysfunction in patients with ACLF and could contribute to enhanced short-term survival in selected cases. However, clear criteria for initiating TPE have yet to be established. Unresponsiveness to standard medical treatment may serve as a potential surrogate parameter to guide clinical decision-making on an individual basis.
Die Hämostase ist ein physiologisch streng balanciertes System mit gegenregulierenden Mechanismen zwischen Prokoagulation, Antikoagulation, Profibrinolyse und Antifibrinolyse. Abweichungen in Richtung einer Blutungs- oder Thromboembolieneigung sind somit Folgen eines Ungleichgewichtes in diesem System. Die im Routinelabor verfügbaren Gerinnungstests fokussieren auf die Untersuchung prokoagulatorischer Störungen, diese aber auch nur sehr begrenzt, ohne dass dabei die endogenen gegenregulatorischen Mechanismen mitberücksichtigt werden. Epidemiologisch sind die meisten Gerinnungsstörungen erworben, wodurch alle Teile des Gerinnungssystems betroffen sein können. Dieser Umstand erfordert von klinisch tätigen Ärzten daher den kritischen Einsatz solcher Gerinnungstests unter kritischer Betrachtung der Anamnese und der klinischen Zeichen. Der unkritische Einsatz von Gerinnungstests liefert entweder kaum nützliche Ergebnisse oder, im schlimmsten Fall, kann er zu Fehlentscheidungen beitragen.
BACKGROUND:Serial indirect calorimetry instead of prediction of energy expenditure is recommended in critically ill patients. However, the feasibility and the challenges associated with it are not systematically investigated. This prospective study was aimed to investigate the course of measured resting energy expenditure in critically ill adult medical patients, the challenges associated with it and factors that significantly impact variations in energy expenditure. METHOD:Indirect calorimetry was serially performed on critically ill adult medical patients on invasive mechanical ventilation. Data on disease severity, body temperature, vasopressor support and sedation depth as well as nutrition therapy were also recorded. RESULTS:A total of 98 patients (65.3 % males) with a mean age of 66.9 ± 13.5 years were included. Their mean Acute Physiology And Chronic Health Evaluation-II score was 31.4 ± 8.4. There was a total of 600 potential measurement days, out of which indirect calorimetry could be carried out on 452 days (75.3 %). There was a stepwise increase in resting energy expenditure during the first 7 days with a quasi-plateau on day 8 and beyond, amounting to an increase in resting energy expenditure by 19.0 ± 28.7 %. Daily changes in body temperature and the Richmond Agitation and Sedation Scale showed a significant effect on variations in energy expenditure. The study patients received beginning from day 4 onwards 93.6 ± 34.7 % (95 % confidence interval 86.1-101.1 %) of their measured energy expenditure. CONCLUSION:There is a stepwise increase in resting energy expenditure during the first week of critical care among critically ill adult medical patients. Patient-related factors and logistic challenges should be considered regarding indirect calorimetry. Body temperature and the degree of sedation have a significant impact on variations in energy expenditure.