Katie Lei

Early enteral supplementation with key pharmaconutrients improves Sequential Organ Failure Assessment score in critically ill patients with sepsis: Outcome of a randomized, controlled, double-blind trial*

Objective:To assess the safety and efficacy of an early enteral pharmaconutrition supplement containing glutamine dipeptides, antioxidative vitamins and trace elements, and butyrate in critically ill, septic patients. Design:A prospective, randomized, controlled, double-blind clinical trial. Setting:Adult intensive care unit in a university hospital. Patients:Fifty-five critically ill, septic patients requiring enteral feeding. Interventions:Patients received either an enteral supplement (500 mL of Intestamin, Fresenius Kabi) containing conditionally essential nutrients or a control solution via the nasogastric route for up to 10 days. Inclusion occurred within 24 hrs of intensive care unit admission. Additionally, patients received enteral feeding with an immunonutrition formula (experimental group) or standard formula (control group) initiated within 48 hrs after enrollment. Measurements and Main Results:Organ dysfunction was assessed by daily total Sequential Organ Failure Assessment (SOFA) score over the 10-day study period in both patient groups. Patients receiving the experimental supplement showed a significantly faster decline in the regression slopes of delta daily total SOFA score over time compared with control. The difference between the regression coefficients of the two slopes was significant irrespective of the level of analysis: intent to treat −0.32 vs. −0.14, p < .0001; per protocol −0.34 vs. −0.14, p < .0001; and completers (patients receiving ≥80% of the calculated caloric target over a period of 6 days), −0.26 vs. −0.16, p = .0005. Vitamin C, as a marker of supplement absorption, increased from 10.6 (1.9–159.4) &mgr;mol/L (normal range 20–50 &mgr;mol/L) on day 1 to 58.7 (5.4–189.9) &mgr;mol/L by day 3 (p = .002) in the intervention group but remained below the normal range in the control group 17.0 (2.8–78.5) on day 1 and 14.3 (2.4–179.6) on day 3. Serum levels of glycine, serine, arginine, ornithine, vitamin E, and &bgr;-carotene all increased significantly with treatment in the supplementation group. Conclusions:In medical patients with sepsis, early enteral pharmaconutrition with glutamine dipeptides, vitamin C and E, &bgr;-carotene, selenium, zinc, and butyrate in combination with an immunonutrition formula results in significantly faster recovery of organ function compared with control.

A prospective study of the impact of serial troponin measurements on the diagnosis of myocardial infarction and hospital and six-month mortality in patients admitted to ICU with non-cardiac diagnoses

IntroductionTroponin T (cTnT) elevation is common in patients in the Intensive Care Unit (ICU) and associated with morbidity and mortality. Our aim was to determine the epidemiology of raised cTnT levels and contemporaneous electrocardiogram (ECG) changes suggesting myocardial infarction (MI) in ICU patients admitted for non-cardiac reasons.MethodscTnT and ECGs were recorded daily during week 1 and on alternate days during week 2 until discharge from ICU or death. ECGs were interpreted independently for the presence of ischaemic changes. Patients were classified into four groups: (i) definite MI (cTnT ≥15 ng/L and contemporaneous changes of MI on ECG), (ii) possible MI (cTnT ≥15 ng/L and contemporaneous ischaemic changes on ECG), (iii) troponin rise alone (cTnT ≥15 ng/L), or (iv) normal. Medical notes were screened independently by two ICU clinicians for evidence that the clinical teams had considered a cardiac event.ResultsData from 144 patients were analysed (42% female; mean age 61.9 (SD 16.9)). A total of 121 patients (84%) had at least one cTnT level ≥15 ng/L. A total of 20 patients (14%) had a definite MI, 27% had a possible MI, 43% had a cTNT rise without contemporaneous ECG changes, and 16% had no cTNT rise. ICU, hospital and 180-day mortality was significantly higher in patients with a definite or possible MI.Only 20% of definite MIs were recognised by the clinical team. There was no significant difference in mortality between recognised and non-recognised events.At the time of cTNT rise, 100 patients (70%) were septic and 58% were on vasopressors. Patients who were septic when cTNT was elevated had an ICU mortality of 28% compared to 9% in patients without sepsis. ICU mortality of patients who were on vasopressors at the time of cTnT elevation was 37% compared to 1.7% in patients not on vasopressors.ConclusionsThe majority of critically ill patients (84%) had a cTnT rise and 41% met criteria for a possible or definite MI of whom only 20% were recognised clinically. Mortality up to 180 days was higher in patients with a cTnT rise.

Physiological predictors of survival during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome

IntroductionData that provide clinical criteria for the identification of patients likely torespond to high-frequency oscillatory ventilation (HFOV) are scarce. Our aim wasto describe physiological predictors of survival during HFOV in adults with severeacute respiratory distress syndrome (ARDS) admitted to a respiratory failurecenter in the United Kingdom.MethodsElectronic records of 102 adults treated with HFOV were reviewed retrospectively.We used logistic regression and receiving-operator characteristics curve to testassociations with oxygenation and mortality.ResultsPatients had severe ARDS with a mean (SD) Murrays score of 2.98 (0.7). Partialpressure of oxygen in arterial blood to fraction of inspired oxygen(PaO2/FiO2) ratio and oxygenation index improved only insurvivors. The earliest time point at which the two groups differed was at threehours after commencing HFOV. An improvement of >38% inPaO2/FiO2 occurring at any time within the first 72hours, was the best predictor of survival at 30 days (area under the curve (AUC)of 0.83, sensitivity 93%, specificity 78% and a positive likelihood ratio (LR) of4.3). These patients also had a 3.5 fold greater reduction in partial pressure ofcarbon dioxide in arterial blood (PaCO2). Multivariate analysis showedthat HFOV was more effective in younger patients, when instituted early, and inpatients with milder respiratory acidosis.ConclusionsHFOV is effective in improving oxygenation in adults with ARDS, particularly wheninstituted early. Changes in PaO2/FiO2 during the firstthree hours of HFOV can identify those patients more likely to survive.

Use of an Electromagnetic Device Compared With Chest X-ray to Confirm Nasogastric Feeding Tube Position in Critical Care.

BACKGROUND Insertion of nasogastric feeding tubes (NGTs) is common in critical care. However, misplacement is frequent and can carry a significant morbidity. Current methods to confirm position of NGTs are not reliable in this setting. We retrospectively compared the position of NGTs using an electromagnetically guided nasogastric tube (e-NGT) with that demonstrated by chest x-ray (CXR), the proportion of lung placements avoided, and the time taken to establish enteral feeding. METHODS This was a retrospective, observational study undertaken in a tertiary referral, adult intensive care unit between February 2006 and November 2013. Patients were included if they had a radiologically confirmed NGT. All CXRs were independently reviewed by an intensivist to determine position, and a subset of patients had their e-NGT image independently reviewed for quality control. Statistical analysis was in the form of sensitivity and specificity and descriptive where indicated. RESULTS In total, 121 NGT placements in 113 patients were analyzed. We found a sensitivity of 98% (95% confidence interval [CI], 93.9%-99.7%) and a specificity of 100% (95% CI, 48.0%-100.0%) when using the e-NGT compared with CXR. In the subset of 51 independently reviewed e-NGT images, 9 lung placements were avoided. The mean (SD) time from e-NGT placement to CXR was 185 (264.4) minutes and to feeding was 404 (77.8) minutes. CONCLUSION When placed by a dedicated team, e-NGT allowed immediate detection of tube misplacement. As such, if used as the sole method for determining NGT position, e-NGTs minimize feeding delay and the need for multiple CXRs with subsequent cost savings.

Maintaining Normal Levels of Ionized Calcium during Citrate-Based Renal Replacement Therapy Is Associated with Stable Parathyroid Hormone Levels

Background/Aims: Citrate is an effective anticoagulant during continuous renal replacement therapy (CRRT). Previous studies showed raised parathyroid hormone (PTH) levels when aiming for serum ionized calcium [Cai] between 0.8 and 1.1 mmol/l. Our objective was to assess whether citrate-based CRRT with physiologic target systemic [Cai] between 1.12 and 1.20 mmol/l could maintain stable PTH levels. Methods: Measurement of intact PTH (PTHi) in 30 consecutive critically ill patients treated with citrate-based CRRT. Results: Thirty patients [mean age: 70.4 (SD 11.3) years; 56.7% males] were enrolled. Mean serum [Cai] was 1.16 mmol/l (SD 0.09), 1.13 mmol/l (SD 0.09), 1.17 mmol/l (SD 0.05) and 1.16 mmol/l (SD 0.04) at baseline, 12, 24 and 48 h, respectively (p = 0.29). Median PTHi levels (interquartile range) at baseline, 12, 24 and 48 h were 66.5 (43-111), 109 (59.5-151.5), 88.5 (47-133) and 85 pg/ml (53-140), respectively. The differences between baseline and 12 h and across all time points were statistically not significant (p = 0.16 and p = 0.49, respectively). In a mixed-effects model, each 0.1 mmol/l increase in serum [Cai] was associated with a 31.2% decrease in PTHi (p < 0.001). Results were unchanged after adjustment for age, gender, magnesium, phosphate, arterial pH and time spent on CRRT. Conclusions: Maintaining systemic [Cai] within the physiologic range was associated with stable PTHi levels.

Cardiac Troponin Release is Associated with Biomarkers of Inflammation and Ventricular Dilatation During Critical Illness.

Introduction: Troponin release is common during critical illness. We hypothesized that there was an association between cardiac troponin T (cTnT) and biomarkers of systemic inflammation and ventricular dilatation. Methods: In an observational prospective cohort study, we enrolled consecutive adult patients admitted for noncardiac reasons to the intensive care unit (ICU) in two tertiary care centers. We measured cTnT, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and N-terminal pro brain natriuretic peptide (NT-proBNP) daily in the first week, and on alternate days in the second week. Using a peak cTnT cutoff ≥15 ng/L and concomitant changes on electrocardiogram, patients were categorized as “definite myocardial infarction (MI),” “possible MI,” “cTnT rise only,” or “no cTnT rise.” Within each group, associations between CRP, IL-6, PCT, NT-proBNP, and cTnT were investigated using mixed effect models. Results: One hundred seventy-two patients were included in the analysis of whom 84% had a cTnT rise ≥15 ng/L. Twenty-one patients (12%) had a definite MI, 51 (30%) had a possible MI, and 73 (42%) had a cTnT rise only. At the time of peak cTnT, 71% of patients were septic and 67% were on vasopressors. Multivariable analysis showed a significant association between cTnT and IL-6 in all patients with a cTnT rise independent of age, gender, renal function, and cardiovascular risk factors. In patients without a definite MI, cTnT levels were significantly associated with PCT and NT-proBNP values. In patients without elevated cTnT levels, there was no associated NT-proBNP rise. Conclusions: In ICU patients admitted for non-cardiac reasons, serial cTnT levels were independently associated with markers of systemic inflammation and NT-proBNP.

Filter survival time and requirement of blood products in patients with severe sepsis receiving drotrecogin alfa (activated) and requiring renal replacement therapy

IntroductionDrotrecogin alfa (activated) (DrotAA) is licensed in the United States and the European Union for the treatment of severe sepsis with multiple organ failure. Patients with severe sepsis on renal replacement therapy (RRT), who typically receive additional anticoagulation to prevent circuit clotting, may be at higher risk of bleeding when DrotAA is administered in addition to standard anticoagulation. However, the effects of DrotAA on filter duration in the absence of additional anticoagulation have not been established. The aim of this study was to analyse the filter survival time (FST), and to quantify the requirement of packed red cells (PRC) and blood products during DrotAA infusion.MethodsThis was a single-centre, retrospective observational study conducted in an adult intensive care unit (ICU). Thirty-five patients with severe sepsis who had received both RRT and DrotAA were identified, and all relevant clinical and laboratory data were retrieved from the departmental electronic patient record. We compared haemofilter parameters, requirement of blood products and haemodynamic data recorded during RRT and the infusion of DrotAA with those recorded on RRT with standard anticoagulation after the DrotAA infusion had been completed (post-DrotAA).ResultsThe proportion of filter changes due to filter clotting was similar during DrotAA infusion and with conventional anticoagulation post-DrotAA infusion. There was no difference in the FST and filter parameters during DrotAA in the presence or absence of additional anticoagulation with heparin or epoprostenol. A similar proportion of patients required red cell transfusion, although a greater proportion of patients received platelet and fresh frozen plasma during DrotAA infusion compared with the post-DrotAA period with no difference between medical and surgical patients.ConclusionsAdditional anticoagulation during DrotAA infusion does not appear to improve FST. The use of DrotAA in patients with severe sepsis requiring RRT is safe and is not associated with an increased need for PRC transfusion or major bleeding events.

Electromagnetically guided bedside placement of post-pyloric feeding tubes in critical care

Post-pyloric feeding is recommended in critically ill patients with gastro-intestinal intolerance. However, traditional placement methods are logistically difficult and carry potential risks. The authors retrospectively compared the position of post-pyloric feeding tubes (PPFTs) using an electromagnetic device that demonstrated by X-ray and analysed the complication rates, proportion of lung placements avoided and the time taken to establish enteral feeding. Forty placements in 37 mechanically ventilated patients were analysed; there was a success rate of 87.5%. Sensitivity and specificity were 77% (95% CI 59.9-89.6%) and 100% (95% CI 48.0-100%). Five lung placements were identified in real time and therefore avoided. The mean (SD) time from PPFT placement to X-ray was 134 minutes (± 139 minutes) and, to feeding, 276 minutes (± 213 minutes). In conclusion, placement of PPFT using an electromagnetic device carries a high success rate, is safe and feasible to undertake at the bedside in mechanically ventilated patients.

Vitamin D levels in critically ill patients with acute kidney injury: a protocol for a prospective cohort study (VID-AKI)

Introduction Acute kidney injury (AKI) affects more than 50% of critically ill patients. The formation of calcitriol, the active vitamin D metabolite, from the main inactive circulating form, 25-hydroxyvitamin D (25(OH)D), occurs primarily in the proximal renal tubules. This results in a theoretical basis for reduction in levels of calcitriol over the course of an AKI. Vitamin D deficiency is highly prevalent in critically ill adults, and has been associated with increased rates of sepsis, longer hospital stays and increased mortality. The primary objective of this study is to perform serial measurements of 25(OH)D and calcitriol (1,25(OH)2D), as well as parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels, in critically ill adult patients with and without AKI, and to determine whether patients with AKI have significantly lower vitamin D metabolite concentrations. The secondary objectives are to describe dynamic changes in vitamin D metabolites, PTH and FGF23 during critical illness; to compare vitamin D metabolite concentrations in patients with AKI with and without renal replacement therapy; and to investigate whether there is an association between vitamin D status and outcomes. Methods and analysis 230 general adult intensive care patients will be recruited. The AKI arm will include 115 critically ill patients with AKI Kidney Disease Improving Global Outcome stage II or stage III. The comparison group will include 115 patients who require cardiovascular or respiratory support, but who do not have AKI. Serial measurements of vitamin D metabolites and associated hormones will be taken on prespecified days. Patients will be recruited from two large teaching Trusts in England. Data will be analysed using standard statistical methods. Ethics and dissemination Ethical approval was obtained. Upon completion, the study team will submit the study report for publication in a peer-reviewed scientific journal and for conference presentation. Trial registration number NCT02869919; Pre-results.