A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice.

The preferential use of the oral/enteral route in critically ill patients over gut rest is uniformly recommended and applied. This article provides practical guidance on enteral nutrition in compliance with recent American and European guidelines. Low-dose enteral nutrition can be safely started within 48 h after admission, even during treatment with small or moderate doses of vasopressor agents. A percutaneous access should be used when enteral nutrition is anticipated for ≥ 4 weeks. Energy delivery should not be calculated to match energy expenditure before day 4-7, and the use of energy-dense formulas can be restricted to cases of inability to tolerate full-volume isocaloric enteral nutrition or to patients who require fluid restriction. Low-dose protein (max 0.8 g/kg/day) can be provided during the early phase of critical illness, while a protein target of > 1.2 g/kg/day could be considered during the rehabilitation phase. The occurrence of refeeding syndrome should be assessed by daily measurement of plasma phosphate, and a phosphate drop of 30% should be managed by reduction of enteral feeding rate and high-dose thiamine. Vomiting and increased gastric residual volume may indicate gastric intolerance, while sudden abdominal pain, distension, gastrointestinal paralysis, or rising abdominal pressure may indicate lower gastrointestinal intolerance.

Nutrition Therapy in Australia and New Zealand Intensive Care Units: An International Comparison Study.

BACKGROUND: The Augmented Versus Routine Approach to Giving Energy Trial (TARGET) is the largest blinded enteral nutrition (EN) intervention trial evaluating energy delivery to be conducted in the critically ill. To determine the external validity of TARGET results, nutrition practices in intensive care units (ICUs) in Australia and New Zealand (ANZ) are described and compared with international practices. METHODS: This was a retrospective analysis of prospectively collected data for the International Nutrition Surveys, 2007-2013. Data are presented as mean (SD). RESULTS: A total of 17,154 patients (ANZ: n = 2776 vs international n = 14,378) from 923 ICUs (146 and 777, respectively) were included. EN was the most common route of feeding (ANZ: 85%, n = 2365 patients vs international: 84%, n = 12,034; P = .258), and EN concentration was also similar (<1.25 kcal/mL ANZ: 70%, n = 12,396 vs international: 65%, n = 56,891 administrations; P < .001). Protein delivery was substantially below the estimated prescriptions but similar between the regions (0.6 [0.4] g/kg/day vs 0.6 [0.4] g/kg/day; P = .849). Patients in ANZ received slightly more energy (1133 [572] vs 948[536] kcal/day; P < .001), possibly because more energy was prescribed (1947 [348] vs 1747 [376] kcal/day; P < .001), nutrition protocols were more commonly used (98% vs 75%; P < .001) and included recommendations for therapies such as prokinetic agents (87% vs 51%, n = 399; P < .001) and small bowel feeding (62% vs 40%; P < .001) when compared with international ICUs. CONCLUSIONS: Key elements of nutrition practice are similar in ANZ and international ICUs. These data can be used to determine the external validity and relevance of TARGET results.

Pharmacokinetics of piperacillin in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration.

Background: Piperacillin is a ß-lactam penicillin antibiotic commonly used for the empirical therapy of sepsis and other hospital-acquired infections. However, knowledge regarding the effect of sustained low-efficiency diafiltration (SLED-f), a technique increasingly being used in ICUs, on piperacillin pharmacokinetics (PK) and dosing in critically ill patients is lacking. Objectives: To describe the PK of piperacillin during SLED-f and compare the results with those reported for other forms of renal replacement therapies. Methods: Serial blood samples were collected at pre- and post-filter ports within the SLED-f circuit during SLED-f in one session and from an arterial catheter during sampling without SLED-f. Piperacillin concentrations were measured using a validated chromatography method. Non-compartmental PK analysis of the data was performed. Results: The median clearance and area under the concentration-time curve during SLED-f were 6 L/h and 532 mg·h/L, respectively. Fifty-eight percent of piperacillin was cleared by a single SLED-f session (6 h) compared with previous reports of 30%-45% clearance by a 3.5 h intermittent haemodialysis session. Clearance, half-life and area under the concentration-time curve during SLED-f obtained from this study were comparable with those reported in the post-dilution mode of continuous veno-venous haemodiafiltration studies. Conclusions: As it can be challenging to accurately predict when SLED-f will be initiated in the critically ill, a maintenance dose of at least 4 g every 12 h with at least a 2 g replacement dose post-SLED-f would be a practical approach to piperacillin dosing in ICU patients with anuria receiving SLED-f with a duration similar to the current study.

Using Population Pharmacokinetic Modeling and Monte Carlo Simulations To Determine whether Standard Doses of Piperacillin in Piperacillin-Tazobactam Regimens Are Adequate for the Management of Febrile Neutropenia.

Changes in the pharmacokinetics of piperacillin in febrile neutropenic patients have been reported to result in suboptimal exposures. This study aimed to develop a population pharmacokinetic model for piperacillin and perform dosing simulation to describe optimal dosing regimens for hematological malignancy patients with febrile neutropenia. Concentration-time data were obtained from previous prospective observational pharmacokinetic and interventional therapeutic drug monitoring studies. Nonparametric population pharmacokinetic analysis and Monte Carlo dosing simulations were performed with the Pmetrics package for R. A two-compartment model, with between-subject variability for clearance (CL), adequately described the data from 37 patients (21 males, age of 59 ± 12 years [means ± standard deviations] and weight of 77 ± 16 kg). Parameter estimates were CL of 18.0 ± 4.8 liters/h, volume of distribution of the central compartment of 14.3 ± 7.3 liters, rate constant for piperacillin distribution from the central to peripheral compartment of 1.40 ± 1.35 h-1, and rate constant for piperacillin distribution from the peripheral to central compartment of 4.99 ± 7.81 h-1 High creatinine clearance (CLCR) was associated with reduced probability of target attainment (PTA). Extended and continuous infusion regimens achieved a high PTA of >90% for an unbound concentration of piperacillin remaining above the MIC (fT>MIC) of 50%. Only continuous regimens achieved >90% PTA for 100% fT>MIC when CLCR was high. The cumulative fraction of response (FTA, for fractional target attainment) was suboptimal (<85%) for conventional regimens for both empirical and directed therapy considering 50% and 100% fT>MIC FTA was maximized with prolonged infusions. Overall, changes in piperacillin pharmacokinetics and the consequences on therapeutic dosing requirements appear similar to those observed in intensive care patients. Guidelines should address the altered dosing needs of febrile neutropenic patients exhibiting high CLCR or with known/presumed infections from high-MIC bacteria.

Can therapeutic drug monitoring optimize exposure to piperacillin in febrile neutropenic patients with haematological malignancies? A randomized controlled trial.

OBJECTIVES: The objectives of this study were to describe piperacillin exposure in febrile neutropenia patients and determine whether therapeutic drug monitoring (TDM) can be used to increase the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets. METHODS: In a prospective randomized controlled study (Australian New Zealand Registry, ACTRN12615000086561), patients were subjected to TDM for 3 consecutive days. Dose was adjusted in the intervention group to achieve a free drug concentration above the MIC for 100% of the dose interval (100% fT>MIC), which was also the primary outcome measure. The secondary PK/PD target was 50% fT>MIC. Duration of fever and days to recovery from neutropenia were recorded. RESULTS: Thirty-two patients were enrolled. Initially, patients received 4.5 g of piperacillin/tazobactam every 8 h or every 6 h along with gentamicin co-therapy in 30/32 (94%) patients. At the first TDM, 7/32 (22%) patients achieved 100% fT>MIC and 12/32 (38%) patients achieved 50% fT>MIC. Following dose adjustment, 11/16 (69%) of intervention patients versus 3/16 (19%) of control patients (P = 0.012) attained 100% fT>MIC, and 15/16 (94%) of intervention patients versus 5/16 (31%) of control patients (P = 0.001) achieved 50% fT>MIC. After the third TDM, the proportion of patients attaining 100% fT>MIC improved from a baseline 3/16 (19%) to 11/15 (73%) in the intervention group, while it declined from 4/16 (25%) to 1/15 (7%) in the control group. No difference was noted in the duration of fever and days to recovery from neutropenia. CONCLUSIONS: Conventional doses of piperacillin/tazobactam may not offer adequate piperacillin exposure in febrile neutropenic patients. TDM provides useful feedback of dosing adequacy to guide dose optimization.