Identification of novel biomarkers in critically ill patients

This thesis summarizes publications of prospective, non-interventional studies on the identification of novel biomarkers in critical care medicine. Biomarkers in the context of this thesis are laboratory values that are determined from the blood of patients who are treated on an intensive care unit. They are used in clinical routine for diagnosis, prognosticate and monitor treatment. For clinical applicability, biomarkers must have appropriate statistical test characteristics to enable distinction between different states of disease. Beyond that, biomarkers should be easy to obtain, rapidly measurable, and generalizable for instant interpretation in the clinical context and prompt decision making to favourably influence the course of the disease. The aim of this thesis was to evaluate the significance, regulation, diagnostic and prognostic value of novel biomarkers measured in the blood of critical ill patients

An Examination of Oral Fed Post-Trauma Patients for Calorie and Protein Consumption as a Percentage of Estimated Needs, and How it Impacts Length of Hospital Stay and Wound Healing

Due to rising costs of healthcare, clinicians are responsible for decreasing costs by providing care that moves the patient from injury, to recovery, to discharge within a matter of just a few days. The Registered Dietitian is responsible for the nutrition assessment and nutrition diagnosis, nutrition prescription and plan, and for monitoring the patient to achieve nutritional repletion within this short time frame. Concerns for patients who require nursing staff and caregivers for feeding are evident, especially when increased demands are being placed on the nursing staff. This study aims to determine whether or not “feeder patients” are at a higher risk for malnutrition, which could potentially result in delayed discharge, poor rate of wound healing, and increased costs to the institution

Ventilatory ratio : a simple bedside index to monitor ventilatory efficiency

A lack of a simple index that monitors ventilatory efficiency at the bedside has meant that oxygenation has been the predominant variable that is used to monitor adequacy of ventilatory strategies and disease severity in mechanically ventilated patients. Due to complexities in its measurement, deadspace ventilation, the traditional method to track ventilatory failure, has failed to become integral in the management of mechanically ventilated patients. Ventilatory ratio (VR) is an easy to calculate index that uses variables measured at the bedside: [Mathematical equation appears here. To view, please open pdf attachment] where [Symbols appears here. To view, please open pdf attachment] is taken to be 100 ml.kg-1.min-1 based on predicted body weight and [Symbols appears here. To view, please open pdf attachment] is taken to be 5 kPa. Physiological analysis of VR dictates that it is influenced by deadspace fraction and CO2 production. Physiological analysis of VR was validated in a benchside lung model and a high fidelity computational cardiopulmonary physiology model. The impact of CO2 production on VR was investigated in patients undergoing laparoscopic surgery who received exogenous intraperitoneal CO2. This showed that delta values of the 2 variables were linear. The variability of CO2 production was examined in ICU patients and results of the study showed that variability of CO2 production was small. In an ICU population correlation of VR was stronger with deadspace in comparison to CO2 production. Of these two variables, deadspace had the greater effect on VR. The clinical uses of VR were examined in 4 databases of ICU patients. VR was significantly higher in non-survivors compared to survivors. Higher values of VR were associated with increased mortality and more ventilator days. A rising values of VR over time was also associated with worse outcome. VR is a simple bedside index that provides clinicians with useful information regarding ventilatory efficiency and is associated with outcome

Separator fluid volume requirements in multi-infusion settings

INTRODUCTION. Intravenous (IV) therapy is a widely used method for the administration of medication in hospitals worldwide. ICU and surgical patients in particular often require multiple IV catheters due to incompatibility of certain drugs and the high complexity of medical therapy. This increases discomfort by painful invasive procedures, the risk of infections and costs of medication and disposable considerably. When different drugs are administered through the same lumen, it is common ICU practice to flush with a neutral fluid between the administration of two incompatible drugs in order to optimally use infusion lumens. An important constraint for delivering multiple incompatible drugs is the volume of separator fluid that is sufficient to safely separate them. OBJECTIVES. In this pilot study we investigated whether the choice of separator fluid, solvent, or administration rate affects the separator volume required in a typical ICU infusion setting. METHODS. A standard ICU IV line (2m, 2ml, 1mm internal diameter) was filled with methylene blue (40 mg/l) solution and flushed using an infusion pump with separator fluid. Independent variables were solvent for methylene blue (NaCl 0.9% vs. glucose 5%), separator fluid (NaCl 0.9% vs. glucose 5%), and administration rate (50, 100, or 200 ml/h). Samples were collected using a fraction collector until <2% of the original drug concentration remained and were analyzed using spectrophotometry. RESULTS. We did not find a significant effect of administration rate on separator fluid volume. However, NaCl/G5% (solvent/separator fluid) required significantly less separator fluid than NaCl/NaCl (3.6 ± 0.1 ml vs. 3.9 ± 0.1 ml, p <0.05). Also, G5%/G5% required significantly less separator fluid than NaCl/NaCl (3.6 ± 0.1 ml vs. 3.9 ± 0.1 ml, p <0.05). The significant decrease in required flushing volume might be due to differences in the viscosity of the solutions. However, mean differences were small and were most likely caused by human interactions with the fluid collection setup. The average required flushing volume is 3.7 ml. CONCLUSIONS. The choice of separator fluid, solvent or administration rate had no impact on the required flushing volume in the experiment. Future research should take IV line length, diameter, volume and also drug solution volumes into account in order to provide a full account of variables affecting the required separator fluid volume

Relationship between Neutrophil to Lymphocyte Ratio with Diaphragm Thickness in Critical Patients

Abstract &nbsp; Background: The cause of weaning failure is multifactorial. One of the causes was Ventilator Induced Diaphragm Dysfunction (VIDD) due to thinning process of the diaphragm thickness. Decreased diaphragm muscle mass might occur due to inflammatory process. Methods: The study was an observational analytic study from September 2018 to January 2019 in Mohammad Hoesin Hospital, Palembang – Indonesia. Ethical appoval for the study was obtained from Ethics Committee and subjects were recruited after signing the informed consents. Only 30 subjects were involved in the end of the study. About 6 mL of blood sample from cubital vein was withdrawn from each subject to measure neutrophils and lymphocytes. Patients’ diaphragm thickness was measured by using ultrasonography on 0th, 3rd, 5th day. Collected data were then analyzed with STATA 15. Results: The chi-square test showed that the relationship of NLR (neutophil to lymphocyte ratio) of the 0th day to the decrease in diaphragm thickness on the 3rd day was not significant (p = 0.254), while the decrease in diaphragm thickness on the 5th day was significant (p = 0.015). Subjects with initial NLR values &gt;7 had a significant higher risk of having decreased diaphragm thickness compared to subjects with initial NLR values ​​≤7 (RR = 1.62 (0.99-2.64); p-value = 0.003). Conclusion: Neutrophil to lymphocyte ratio affected the decrease of diaphragm thickness in patients using mechanical ventilation

Risk Adjustment In Neurocritical care (RAIN)--prospective validation of risk prediction models for adult patients with acute traumatic brain injury to use to evaluate the optimum location and comparative costs of neurocritical care: a cohort study.

OBJECTIVES: To validate risk prediction models for acute traumatic brain injury (TBI) and to use the best model to evaluate the optimum location and comparative costs of neurocritical care in the NHS. DESIGN: Cohort study. SETTING: Sixty-seven adult critical care units. PARTICIPANTS: Adult patients admitted to critical care following actual/suspected TBI with a Glasgow Coma Scale (GCS) score of < 15. INTERVENTIONS: Critical care delivered in a dedicated neurocritical care unit, a combined neuro/general critical care unit within a neuroscience centre or a general critical care unit outside a neuroscience centre. MAIN OUTCOME MEASURES: Mortality, Glasgow Outcome Scale - Extended (GOSE) questionnaire and European Quality of Life-5 Dimensions, 3-level version (EQ-5D-3L) questionnaire at 6 months following TBI. RESULTS: The final Risk Adjustment In Neurocritical care (RAIN) study data set contained 3626 admissions. After exclusions, 3210 patients with acute TBI were included. Overall follow-up rate at 6 months was 81%. Of 3210 patients, 101 (3.1%) had no GCS score recorded and 134 (4.2%) had a last pre-sedation GCS score of 15, resulting in 2975 patients for analysis. The most common causes of TBI were road traffic accidents (RTAs) (33%), falls (47%) and assault (12%). Patients were predominantly young (mean age 45 years overall) and male (76% overall). Six-month mortality was 22% for RTAs, 32% for falls and 17% for assault. Of survivors at 6 months with a known GOSE category, 44% had severe disability, 30% moderate disability and 26% made a good recovery. Overall, 61% of patients with known outcome had an unfavourable outcome (death or severe disability) at 6 months. Between 35% and 70% of survivors reported problems across the five domains of the EQ-5D-3L. Of the 10 risk models selected for validation, the best discrimination overall was from the International Mission for Prognosis and Analysis of Clinical Trials in TBI Lab model (IMPACT) (c-index 0.779 for mortality, 0.713 for unfavourable outcome). The model was well calibrated for 6-month mortality but substantially underpredicted the risk of unfavourable outcome at 6 months. Baseline patient characteristics were similar between dedicated neurocritical care units and combined neuro/general critical care units. In lifetime cost-effectiveness analysis, dedicated neurocritical care units had higher mean lifetime quality-adjusted life-years (QALYs) at small additional mean costs with an incremental cost-effectiveness ratio (ICER) of £14,000 per QALY and incremental net monetary benefit (INB) of £17,000. The cost-effectiveness acceptability curve suggested that the probability that dedicated compared with combined neurocritical care units are cost-effective is around 60%. There were substantial differences in case mix between the 'early' (within 18 hours of presentation) and 'no or late' (after 24 hours) transfer groups. After adjustment, the 'early' transfer group reported higher lifetime QALYs at an additional cost with an ICER of £11,000 and INB of £17,000. CONCLUSIONS: The risk models demonstrated sufficient statistical performance to support their use in research but fell below the level required to guide individual patient decision-making. The results suggest that management in a dedicated neurocritical care unit may be cost-effective compared with a combined neuro/general critical care unit (although there is considerable statistical uncertainty) and support current recommendations that all patients with severe TBI would benefit from transfer to a neurosciences centre, regardless of the need for surgery. We recommend further research to improve risk prediction models; consider alternative approaches for handling unobserved confounding; better understand long-term outcomes and alternative pathways of care; and explore equity of access to postcritical care support for patients following acute TBI. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Early Fluid Balance Is Associated with 90-Day Mortality in Patients Receiving Continuous Renal Replacement Therapy

Continuous renal replacement therapy (CRRT) is widely used to control fluid balance, but the optimal fluid balance to improve the prognosis of patients remains debated. Appropriate fluid management may depend on hemodynamic status. We investigated the association between 90-day mortality and fluid balance/mean arterial pressure (MAP) in patients receiving CRRT. This single-center retrospective study was conducted between May 2018 and March 2021. Based on the cumulative fluid balance at 72 h after initiation of CRRT, the cases were divided into negative ( 0 mL) fluid balance groups. Ninety-day mortality was higher in the positive fluid balance group (p=0.009). At 4 h before and after CRRT initiation, the mean MAP was lower in the positive fluid balance group (p<0.05). After multivariate cox adjustment, 72-h positive fluid balance was independently associated with 90-day mortality (p=0.004). In addition, the cumulative fluid balance was associated with 90-day mortality (p<0.05) in cases without shock, high APACHE II score, sepsis, dialysis dependence, or vasopressor use. A 72-h positive fluid balance was associated with 90-day mortality in patients receiving CRRT