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1.
A Model-Based Approach to Assess Unstable Creatinine Clearance in Critically Ill Patients.
Ullah, S, Zoller, M, Jaehde, U, Huseyn-Zada, M, Weig, T, Fuhr, U, Arshad, U, Zander, J, Taubert, M
Clinical pharmacology and therapeutics. 2021;(5):1240-1249
Abstract
Creatinine clearance is an important tool to describe the renal elimination of drugs in pharmacokinetic (PK) evaluations and clinical practice. In critically ill patients, unstable kidney function invalidates the steady-state assumption underlying equations, such as Cockcroft-Gault. Although measured creatinine clearance (mCrCL) is often used in nonsteady-state situations, it assumes that observed data are error-free, neglecting frequently occurring errors in urine collection. In contrast, compartmental nonlinear mixed effects models of creatinine allow to describe dynamic changes in kidney function while explicitly accounting for a residual error associated with observations. Based on 530 serum and 373 urine creatinine observations from 138 critically ill patients, a one-compartment creatinine model with zero-order creatinine generation rate (CGR) and first-order CrCL was evaluated. An autoregressive approach for interoccasion variability provided a distinct model improvement compared to a classical approach (Δ Akaike information criterion (AIC) -49.0). Fat-free mass, plasma urea concentration, age, and liver transplantation were significantly related to CrCL, whereas weight and sex were linked to CGR. The model-based CrCL estimates were superior to standard approaches to estimate CrCL (or glomerular filtration rate) including Cockcroft-Gault, mCrCL, four-variable modification of diet in renal disease (MDRD), six-variable MDRD, and chronic kidney disease epidemiology collaboration as a covariate to describe cefepime and meropenem PKs in terms of objective function value. In conclusion, a dynamic model of creatinine kinetics provides the means to estimate actual CrCL despite dynamic changes in kidney function, and it can easily be incorporated into population PK evaluations.
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2.
Promotion of Regular Oesophageal Motility to Prevent Regurgitation and Enhance Nutrition Intake in Long-Stay ICU Patients. A Multicenter, Phase II, Sham-Controlled, Randomized Trial: The PROPEL Study.
Heyland, DK, Marquis, F, Lamontagne, F, Albert, M, Turgeon, AF, Khwaja, KA, Garland, A, Hall, R, Chapman, MG, Kutsiogannis, DJ, et al
Critical care medicine. 2020;(3):e219-e226
Abstract
OBJECTIVES To evaluate the effect of esophageal stimulation on nutritional adequacy in critically ill patients at risk for enteral feeding intolerance. DESIGN A multicenter randomized sham-controlled clinical trial. SETTING Twelve ICUs in Canada. PATIENTS We included mechanically ventilated ICU patients who were given moderate-to-high doses of opioids and expected to remain alive and ventilated for an additional 48 hours and who were receiving enteral nutrition or expected to start imminently. INTERVENTIONS Patients were randomly assigned 1:1 to esophageal stimulation via an esophageal stimulating catheter (E-Motion Tube; E-Motion Medical, Tel Aviv, Israel) or sham treatment. All patients were fed via these catheters using a standardized feeding protocol. MEASUREMENTS AND MAIN RESULTS The co-primary outcomes were proportion of caloric and protein prescription received enterally over the initial 7 days following randomization. Among 159 patients randomized, the modified intention-to-treat analysis included 155 patients: 73 patients in the active treatment group and 82 in the sham treatment group. Over the 7-day study period, the percent of prescribed caloric intake (± SE) received by the enteral route was 64% ± 2 in the active group and 65% ± 2 in sham patients for calories (difference, -1; 95% CI, -8 to 6; p = 0.74). For protein, it was 57% ± 3 in the active group and 60% ± 3 in the sham group (difference, -3; 95% CI, -10 to 3; p = 0.30). Compared to the sham group, there were more serious adverse events reported in the active treatment group (13 vs 6; p = 0.053). Clinically important arrhythmias were detected by Holter monitoring in 36 out of 70 (51%) in the active group versus 22 out of 76 (29%) in the sham group (p = 0.006). CONCLUSIONS Esophageal stimulation via a special feeding catheter did not improve nutritional adequacy and was associated with increase risk of harm in critically ill patients.
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3.
The Effect of IV Amino Acid Supplementation on Mortality in ICU Patients May Be Dependent on Kidney Function: Post Hoc Subgroup Analyses of a Multicenter Randomized Trial.
Zhu, R, Allingstrup, MJ, Perner, A, Doig, GS, ,
Critical care medicine. 2018;(8):1293-1301
Abstract
OBJECTIVES We investigated whether preexisting kidney function determines if ICU patients may benefit from increased (2.0 g/kg/d) protein intake. DESIGN Post hoc, hypothesis-generating, subgroup analysis of a multicenter, phase 2, randomized clinical trial. All analyses were conducted by intention to treat and maintained group allocation. Ninety-day mortality was the primary outcome. SETTING ICUs of 16 hospitals throughout Australia and New Zealand. PATIENTS Adult critically ill patients expected to remain in the study ICU for longer than 2 days. INTERVENTIONS Random allocation to receive a daily supplement of up to 100 g of IV amino acids to achieve a total protein intake of 2.0 g/kg/d or standard nutrition care. MEASUREMENTS AND MAIN RESULTS A total of 474 patients were randomized: 235 to standard care and 239 to IV amino acid supplementation. There was a statistically significant interaction between baseline kidney function and supplementation with study amino acids (p value for interaction = 0.026). Within the subgroup of patients with normal kidney function at randomization, patients who were allocated to receive the study amino acid supplement were less likely to die before study day 90 (covariate-adjusted risk difference, -7.9%; 95% CI, -15.1 to -0.7; p = 0.034). Furthermore, amino acid supplementation significantly increased estimated glomerular filtration rate in these patients (repeated-measures treatment × time interaction p = 0.009). Within the subgroup of patients with baseline kidney dysfunction and/or risk of progression of acute kidney injury, a significant effect of the study intervention on mortality was not found (covariate-adjusted risk difference, -0.6%; 95% CI, -16.2 to 15.2; p = 0.95). CONCLUSIONS In this post hoc, hypothesis-generating, subgroup analysis, we observed reduced mortality and improved estimated glomerular filtration rate in ICU patients with normal kidney function who were randomly allocated to receive increased protein intake (up to 2.0 g/kg/d). We strongly recommend confirmation of these results in trials with low risk of bias before this treatment is recommended for routine care.
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4.
Blind bedside postpyloric placement of spiral tube as rescue therapy in critically ill patients: a prospective, tricentric, observational study.
Lv, B, Hu, L, Chen, L, Hu, B, Zhang, Y, Ye, H, Sun, C, Zhang, X, Lan, H, Chen, C
Critical care (London, England). 2017;(1):248
Abstract
BACKGROUND Various special techniques for blind bedside transpyloric tube placement have been introduced into clinical practice. However, transpyloric spiral tube placement facilitated by a blind bedside method has not yet been reported. The objective of this prospective study was to evaluate the safety and efficiency of blind bedside postpyloric placement of a spiral tube as a rescue therapy subsequent to failed spontaneous transpyloric migration in critically ill patients. METHODS This prospective, tricentric, observational study was conducted in the intensive care units (ICUs) of three tertiary hospitals. A total of 127 consecutive patients with failed spontaneous transpyloric spiral tube migration despite using prokinetic agents and still required enteral nutrition for more than 3 days were included. The spiral tube was inserted postpylorically using the blind bedside technique. All patients received metoclopramide intravenously prior to tube insertion. The exact tube tip position was determined by radiography. The primary efficacy endpoint was the success rate of postpyloric spiral tube placement. Secondary efficacy endpoints were success rate of a spiral tube placed in the third portion of the duodenum (D3) or beyond, success rate of placement in the proximal jejunum, time to insertion, length of insertion, and number of attempts. Safety endpoints were metoclopramide-related and major adverse tube-associated events. RESULTS In 81.9% of patients, the spiral feeding tubes were placed postpylorically; of these, 55.1% were placed in D3 or beyond and 33.9% were placed in the proximal jejunum, with a median time to insertion of 14 min and an average number of attempts of 1.4. The mean length of insertion was 95.6 cm. The adverse event incidence was 26.0%, and no serious adverse event was observed. CONCLUSIONS Blind bedside postpyloric placement of a spiral tube, as a rescue therapy subsequent to failed spontaneous transpyloric migration in critically ill patients, is safe and effective. This technique may facilitate the early initiation of postpyloric feeding in the ICU. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR-OPN-16008206 . Registered on 1 April 2016.
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5.
Space GlucoseControl system for blood glucose control in intensive care patients--a European multicentre observational study.
Blaha, J, Barteczko-Grajek, B, Berezowicz, P, Charvat, J, Chvojka, J, Grau, T, Holmgren, J, Jaschinski, U, Kopecky, P, Manak, J, et al
BMC anesthesiology. 2016;:8
Abstract
BACKGROUND Glycaemia control (GC) remains an important therapeutic goal in critically ill patients. The enhanced Model Predictive Control (eMPC) algorithm, which models the behaviour of blood glucose (BG) and insulin sensitivity in individual ICU patients with variable blood samples, is an effective, clinically proven computer based protocol successfully tested at multiple institutions on medical and surgical patients with different nutritional protocols. eMPC has been integrated into the B.Braun Space GlucoseControl system (SGC), which allows direct data communication between pumps and microprocessor. The present study was undertaken to assess the clinical performance and safety of the SGC for glycaemia control in critically ill patients under routine conditions in different ICU settings and with various nutritional protocols. METHODS The study endpoints were the percentage of time the BG was within the target range 4.4 - 8.3 mmol.l(-1), the frequency of hypoglycaemic episodes, adherence to the advice of the SGC and BG measurement intervals. BG was monitored, and insulin was given as a continuous infusion according to the advice of the SGC. Nutritional management (enteral, parenteral or both) was carried out at the discretion of each centre. RESULTS 17 centres from 9 European countries included a total of 508 patients, the median study time was 2.9 (1.9-6.1) days. The median (IQR) time-in-target was 83.0 (68.7-93.1) % of time with the mean proposed measurement interval 2.0 ± 0.5 hours. 99.6% of the SGC advices on insulin infusion rate were accepted by the user. Only 4 episodes (0.01% of all BG measurements) of severe hypoglycaemia <2.2 mmol.l(-1) in 4 patients occurred (0.8%; 95% CI 0.02-1.6%). CONCLUSION Under routine conditions and under different nutritional protocols the Space GlucoseControl system with integrated eMPC algorithm has exhibited its suitability for glycaemia control in critically ill patients. TRIAL REGISTRATION ClinicalTrials.gov NCT01523665.
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6.
Neuromuscular electrical stimulation prevents muscle wasting in critically ill comatose patients.
Dirks, ML, Hansen, D, Van Assche, A, Dendale, P, Van Loon, LJ
Clinical science (London, England : 1979). 2015;(6):357-65
Abstract
Fully sedated patients, being treated in the intensive care unit (ICU), experience substantial skeletal muscle loss. Consequently, survival rate is reduced and full recovery after awakening is compromised. Neuromuscular electrical stimulation (NMES) represents an effective method to stimulate muscle protein synthesis and alleviate muscle disuse atrophy in healthy subjects. We investigated the efficacy of twice-daily NMES to alleviate muscle loss in six fully sedated ICU patients admitted for acute critical illness [n=3 males, n=3 females; age 63 ± 6 y; APACHE II (Acute Physiology and Chronic Health Evaluation II) disease-severity-score: 29 ± 2]. One leg was subjected to twice-daily NMES of the quadriceps muscle for a period of 7 ± 1 day whereas the other leg acted as a non-stimulated control (CON). Directly before the first and on the morning after the final NMES session, quadriceps muscle biopsies were collected from both legs to assess muscle fibre-type-specific cross-sectional area (CSA). Furthermore, phosphorylation status of the key proteins involved in the regulation of muscle protein synthesis was assessed and mRNA expression of selected genes was measured. In the CON leg, type 1 and type 2 muscle-fibre-CSA decreased by 16 ± 9% and 24 ± 7% respectively (P<0.05). No muscle atrophy was observed in the stimulated leg. NMES increased mammalian target of rapamycin (mTOR) phosphorylation by 19 ± 5% when compared with baseline (P<0.05), with no changes in the CON leg. Furthermore, mRNA expression of key genes involved in muscle protein breakdown either declined [forkhead box protein O1 (FOXO1); P<0.05] or remained unchanged [muscle atrophy F-box (MAFBx) and muscle RING-finger protein-1 (MuRF1)], with no differences between the legs. In conclusion, NMES represents an effective and feasible interventional strategy to prevent skeletal muscle atrophy in critically ill comatose patients.
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7.
The effects of implementing a nutritional support algorithm in critically ill medical patients.
Sungur, G, Sahin, H, Tasci, S
JPMA. The Journal of the Pakistan Medical Association. 2015;(8):810-4
Abstract
OBJECTIVE To determine the effect of the enteral nutrition algorithm on nutritional support in critically ill medical patients. METHODS The quasi-experimental study was conducted at a medical Intensive Care Unit of a university hospital in central Anatolia region in Turkey from June to December 2008. The patients were divided into two equal groups: the historical group was fed in routine clinical applications, while the study group was fed according to the enteral nutritional algorithm. Prior to collecting data, nurses were trained interactively about enteral nutrition and the nutritional support algorithm. The nutrition of the study group was directed by the nurses. Data were recorded during 3 days of care. SPSS 22 was used for statistical analysis. RESULTS The 40 patients in the study were divided into two equal groups of 20(50%) each. The energy intake of study group was 62% of the prescribed energy requirement on the 1st, 68.5% on the 2nd and 63% on the 3rd day, whereas in the historical group 38%, 56.5% and 60% of the prescribed energy requirement were met. The consumed energy of the historical group on the 1st 2nd and 3rd day was significantly different (p=0.020). In the study group, serum total protein and albumin levels decreased significantly (p<0.05), but pre-albumin and fasting blood glucose levels were not changed on the 1st and 4th day. In the historical group, any of the serum parameters did not change. Enteral nutrition-induced complications, duration of stay in intensive care unit were not significantly different between the groups (p>0.05). CONCLUSIONS The use of standard algorithms for enteral nutrition may be an effective way to meet the nutritional requirements of patients.
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8.
Safety evaluation of a trial of lipocalin-directed sodium bicarbonate infusion for renal protection in at-risk critically ill patients.
Schneider, AG, Bellomo, R, Reade, M, Peck, L, Young, H, Eastwood, GM, Garcia, M, Moore, E, Harley, N
Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine. 2013;(2):126-33
Abstract
BACKGROUND Urine alkalinisation with sodium bicarbonate decreases renal oxidative stress and might attenuate sepsisassociated acute kidney injury (s-AKI). The safety and feasibility of urine alkalinisation in patients at risk of s-AKI has never been tested. METHODS We randomly assigned patients at risk of s-AKI (those with systemic inflammatory response syndrome [SIRS], oliguria and elevated [≥150 µg/L] serum neutrophil gelatinase-associated lipocalin [sNGAL] concentration) to receive sodium bicarbonate (treatment group) or sodium chloride (placebo group) in a 0.5 mmol/kg bolus followed by an infusion of 0.2 mmol/kg/hour. RESULTS Among 50 patients with SIRS and oliguria, 25 (50%) had an elevated sNGAL concentration. Of these, 13 were randomised to receive sodium bicarbonate and 12 to receive sodium chloride infusion. Study drugs were infused for a mean period of 25.9 hours (SD, 10 hours). Severe electrolyte abnormalities occurred in seven patients (28%) (four [30.8%] in the treatment group and three [25%] in the placebo group). These abnormalities resulted in early protocol cessation in six patients (24%) and study drug suspension in one patient (4%). This adverse event rate was judged to be unacceptable and the study was terminated early. There was no difference between the two groups in sNGAL or urinary NGAL concentrations over time, occurrence of acute kidney injury, requirement for renal replacement therapy, hospital length-of-stay or mortality. CONCLUSION Administration of sodium bicarbonate and sodium chloride solutions to patients at risk of s-AKI was associated with frequent major electrolyte abnormalities and early protocol cessation. The tested protocol does not appear safe or feasible.
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9.
Screening and risk factors of exocrine pancreatic insufficiency in critically ill adult patients receiving enteral nutrition.
Wang, S, Ma, L, Zhuang, Y, Jiang, B, Zhang, X
Critical care (London, England). 2013;(4):R171
Abstract
INTRODUCTION Malnutrition is a frequent problem associated with detrimental clinical outcomes in critically ill patients. To avoid malnutrition, most studies focus on the prevention of inadequate nutrition delivery, whereas little attention is paid to the potential role of exocrine pancreatic insufficiency (EPI). In this trial, we aim to evaluate the prevalence of EPI and identify its potential risk factors in critically ill adult patients without preexisting pancreatic diseases. METHODS In this prospective cross-sectional study, we recruited 563 adult patients with critical illnesses. All details of the patients were documented, stool samples were collected three to five days following the initiation of enteral nutrition, and faecal elastase 1 (FE-1) concentrations were assayed using an enzyme-linked immunosorbent assay kit. Blood samples were also taken to determine serum amylase and lipase activity. RESULTS The percentages of recruited patients with EPI (FE-1 concentration <200 μg/g) and severe EPI (FE-1 concentration <100 μg/g) were 52.2% and 18.3%, respectively. The incidences of steatorrhea were significantly different (P < 0.05) among the patients without EPI, with moderate EPI (FE-1 concentration = 100 to 200 μg/g) and severe EPI (FE-1 concentration < 100 μg/g). Both multivariate logistic regression analysis and z-tests indicated that the occurrence of EPI was closely associated with shock, sepsis, diabetes, cardiac arrest, hyperlactacidemia, invasive mechanical ventilation and haemodialysis. CONCLUSIONS More than 50% of critically ill adult patients without primary pancreatic diseases had EPI, and nearly one-fifth of them had severe EPI. The risk factors for EPI included shock, sepsis, diabetes, cardiac arrest, hyperlactacidemia, invasive mechanical ventilation and haemodialysis. TRIAL REGISTRATION NCT01753024.
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10.
Assessment of body cell mass at bedside in critically ill patients.
Savalle, M, Gillaizeau, F, Maruani, G, Puymirat, E, Bellenfant, F, Houillier, P, Fagon, JY, Faisy, C
American journal of physiology. Endocrinology and metabolism. 2012;(3):E389-96
Abstract
Critical illness affects body composition profoundly, especially body cell mass (BCM). BCM loss reflects lean tissue wasting and could be a nutritional marker in critically ill patients. However, BCM assessment with usual isotopic or tracer methods is impractical in intensive care units (ICUs). We aimed to modelize the BCM of critically ill patients using variables available at bedside. Fat-free mass (FFM), bone mineral (Mo), and extracellular water (ECW) of 49 critically ill patients were measured prospectively by dual-energy X-ray absorptiometry and multifrequency bioimpedance. BCM was estimated according to the four-compartment cellular level: BCM = FFM - (ECW/0.98) - (0.73 × Mo). Variables that might influence the BCM were assessed, and multivariable analysis using fractional polynomials was conducted to determine the relations between BCM and these data. Bootstrap resampling was then used to estimate the most stable model predicting BCM. BCM was 22.7 ± 5.4 kg. The most frequent model included height (cm), leg circumference (cm), weight shift (Δ) between ICU admission and body composition assessment (kg), and trunk length (cm) as a linear function: BCM (kg) = 0.266 × height + 0.287 × leg circumference + 0.305 × Δweight - 0.406 × trunk length - 13.52. The fraction of variance explained by this model (adjusted r(2)) was 46%. Including bioelectrical impedance analysis variables in the model did not improve BCM prediction. In summary, our results suggest that BCM can be estimated at bedside, with an error lower than ±20% in 90% subjects, on the basis of static (height, trunk length), less stable (leg circumference), and dynamic biometric variables (Δweight) for critically ill patients.