Nutrition in Sepsis: A Bench-to-Bedside Review.

Nutrition therapy in sepsis is challenging and differs from the standard feeding approach in critically ill patients. The dysregulated host response caused by infection induces progressive physiologic alterations, which may limit metabolic capacity by impairing mitochondrial function. Hence, early artificial nutrition should be ramped-up and emphasis laid on the post-acute phase of critical illness. Caloric dosing is ideally guided by indirect calorimetry, and endogenous energy production should be considered. Proteins should initially be delivered at low volume and progressively increased to 1.3 g/kg/day following shock symptoms wane. Both the enteral and parenteral route can be (simultaneously) used to cover caloric and protein targets. Regarding pharmaconutrition, a low dose glutamine seems appropriate in patients receiving parenteral nutrition. Supplementing arginine or selenium is not recommended. High-dose vitamin C administration may offer substantial benefit, but actual evidence is too limited for advocating its routine use in sepsis. Omega-3 polyunsaturated fatty acids to modulate metabolic processes can be safely used, but non-inferiority to other intravenous lipid emulsions remains unproven in septic patients. Nutrition stewardship, defined as the whole of interventions to optimize nutritional approach and treatment, should be pursued in all septic patients but may be difficult to accomplish within a context of profoundly altered cellular metabolic processes and organ dysfunction caused by time-bound excessive inflammation and/or immune suppression. This review aims to provide an overview and practical recommendations of all aspects of nutritional therapy in the setting of sepsis.

Dosing vitamin C in critically ill patients with special attention to renal replacement therapy: a narrative review.

RATIONALE/METHODS: The primary aim of the present contribution is to find a literature-based agreement on dose adjustments of vitamin C in critically ill patients undergoing renal replacement therapy (RRT). AVAILABLE DATA/STUDY RESULTS: Critical illness is frequently accompanied by severe vitamin C deficiency. High-dose supplementation beneficially affects clinical outcome in small cohorts of patients with sepsis, burn injury, and trauma. There are no specific data on clinical outcomes in patients receiving renal replacement therapy (RRT). Vitamin C plasma concentrations in patients on RRT are comparable to critically ill patients not receiving RRT. Vitamin C is cleared from the circulation during RRT at a rate dependent on the plasma concentration, dose and duration of RRT. Sieving coefficient is about 1. While the dose of RRT is lower than normal renal function, tubular reabsorption is absent. Sparse evidence suggests that vitamin C dosing during continuous RRT should not exceed the dose administered to critically ill patients not receiving continuous RRT. Low plasma concentrations are expected during prolonged RRT because of persistent extracorporeal removal, absent renal reabsorption and enhanced metabolic loss due to circuit-induced oxidative stress. A dosage of twice 1 g vitamin C daily may be necessary to achieve normal plasma concentrations during RRT, but more studies are needed. There is no available evidence that high doses of vitamin C administered over a short period can induce oxalate stones or has pro-oxidant effects. CONCLUSIONS: Supplementing vitamin C 1 g twice daily to critically ill patients has a solid pathophysiological rationale and a good safety profile. Patients on RRT probably need similar doses as critically ill patients not receiving RRT. Intravenous vitamin C in a dose of 2 g/day may be necessary to achieve normal plasma concentrations during RRT. However, data on dose adjustment of vitamin C during intermittent or chronic RRT are sparse and require more thorough pharmacokinetic and dose-response studies.

Unidentified cachexia patients in the oncologic setting: Cachexia UFOs do exist.

OBJECTIVES: Cachexia is an important outcome-modulating parameter in patients with cancer. In the context of a randomized controlled trial on cachexia and nutritional therapy, the TiCaCONCO (Tight Caloric Control in the Cachectic Oncologic Patient) trial, the contacts between patients with cancer and health care practitioners and oncologists were screened. The aim of this retrospective study was to identify in the charts the input of data on body weight (necessary to identify cachexia stage), relevant nutritional data, and nutritional interventions triggered or implemented by oncologists and dietitians. METHODS: In a tertiary, university oncology setting, over a time span of 8 mo (34 wk), the charts of patients admitted to an oncology, gastroenterology, or abdominal surgery unit were screened for the presence of information contributing to a cancer cachexia diagnosis. Data (patient characteristics, tumor type, and location) was gathered. RESULTS: We analyzed 9694 files. Data on body weight was present for >90% of patients. Of the 9694 screening, 118 new diagnoses of cancer were present (1.22% of patient contacts). Information on weight evolution or nutritional status was absent for 54 patients (46%). In contacts between oncologists and patients with cancer, at the time of diagnosis, cachexia was present in 50 patients (42%). In 7 of these patients (14%), no nutritional information was present in the notes. Of the 50 patients with cachexia, only 8 (16%) had a nutritional intervention initiated by the physician. Nutritional interventions were documented in the medical note in 11 patients (9%) in the overall study population. Dietitians made notes regarding nutrition and weight for 49 patients (42%). We could not demonstrate a difference in mortality between cachectic and non-cachectic patients, although numbers are small for analysis. CONCLUSION: Patients newly diagnosed with cancer are not systematically identified as being cachectic and if they are, interventions in the field of nutrition therapy are largely lacking. Important barriers exist between oncologists and dietitians, the former being mandatory to the success of a nutrition trial in cancer.

Modification of Nutrition Therapy During Continuous Renal Replacement Therapy in Critically Ill Pediatric Patients: A Narrative Review and Recommendations.

INTRODUCTION: Nutrition is an important part of treatment in critically ill children. Clinical guidelines for nutrition adaptations during continuous renal replacement therapy (CRRT) are lacking. We collected and evaluated current knowledge on this topic and provide recommendations. METHODS: Questions were produced to guide the literature search in the PubMed database. RESULTS: Evidence is scarce and extrapolation from adult data was often required. CRRT has a direct and substantial impact on metabolism. Indirect calorimetry is the preferred method to assess resting energy expenditure (REE). Moderate underestimation of REE is common but not clinically relevant. Formula-based calculation of REE is inaccurate and not validated in critically ill children on CRRT. The nutrition impact of nonintentional calories delivered as citrate, lactate, and glucose during CRRT must be considered. Quantifying nitrogen balance is not feasible during CRRT. Protein delivery should be increased by 25% to compensate for losses in the effluent. Fats are not removed by CRRT and should not be adapted during CRRT. Electrolyte disturbances are frequently present and should be treated accordingly. Vitamins B1, B6, B9, and C are lost in the effluent and should be adapted to the effluent dose. Trace elements, with the exception of selenium, are not cleared in relevant quantities. Manganese accumulation is of concern because of potential neurotoxicity. CONCLUSION: Current recommendations regarding nutrition support in pediatric CRRT must be extrapolated from adult studies. Recommendations are provided, based on the weak level of evidence. Additional research on this topic is warranted.

The CoCoS trial: Caloric Control in Cardiac Surgery patients promotes survival, an interventional trial with retrospective control.

BACKGROUND & AIMS: Malnutrition is widespread among cardiac surgery patients and is independently related to an adverse postoperative evolution or outcome. We aimed to assess whether nutrition therapy (NT) could alter caloric deficit, morbidity, and mortality in patients scheduled for non-emergency coronary artery bypass graft (CABG) or aortic valve surgery. METHODS: 351 patients undergoing either elective CABG or aortic valve surgery were studied. Patients receiving NT were enrolled from January 2013 until December 2014. A retrospective control group (CT) consisted of 142 matched patients. The primary endpoint was to evaluate whether NT could limit caloric deficit (Intake to Need Deviation). Secondary endpoints addressed the potential effect of NT on morbidity and mortality. Patients were followed for one year after surgery. RESULTS: There was no significant difference in patient, laboratory or mortality profile between the groups. Caloric deficit could be limited in the intervention group, essentially by providing oral feeding and oral supplements. A minority of patients required enteral or parenteral nutrition during their hospital stay. Caloric deficit increased after the second postoperative day because more patients were switched to oral feeding and intravenous infusions were omitted. Combining CABG and aortic valve surgery, male patients in the NT group had significantly less arrhythmia than in the CT group (7% versus 31%; P = 0.0056), while females in the NT group had significantly less pneumonia than in the CT group (7% versus 22%; P = 0.0183). Survival was significantly higher in female NT patients compared to CT patients, both for CABG (100% versus 83%; P = 0.0015) and aortic valve surgery (97% versus 78%; P = 0.0337). CONCLUSION: The results suggest that NT beneficially affects morbidity and mortality in elective cardiac surgery patients. The impact of NT seems more pronounced in women than in men. Registration: Clinicaltrials.gov: NCT02902341.

Nutrition therapy in cachectic cancer patients. The Tight Caloric Control (TiCaCo) pilot trial.

BACKGROUND: Cancer is a common disease and many patients are diagnosed with advanced stages. Due to cancer generalization, patients may become ill-nourished and even cachectic. Malignancy-related cachexia is associated with worsening physical function, reduced tolerance to anticancer therapy and increased mortality. We assessed the effect of a patient-tailored nutritional approach in newly discovered, treatment-naive cancer patients with cachexia. METHODS: In a randomized, single-blinded, controlled pilot study, patients were treated with either intensive, biometric parameter-oriented dietary counseling (nutrition therapy) compared to regular dietary counseling (control), before and during conventional cancer treatment. Twenty patients were enrolled over a one-year period, 10 receiving nutrition therapy and 10 controls. The primary endpoint was recovery of body composition after nutrition therapy. Secondary endpoints declined in morbidity and mortality with nutrition therapy. RESULTS: Average weight evolution in the control group after 3, 6 and 12 months was 0.19 ± 7.87 kg, -9.78 ± 7.00 kg and -5.8 kg, and in the nutrition therapy group 0.69 ± 2.4 kg, 0.77 ± 2.58 kg and 1.29 ± 3.76 kg. Control patients had a significantly longer average hospital stay than subjects from the nutrition therapy group (37.6 vs. 3.4 days). Eight nutrition therapy patients and 1 control patient were still alive after 2 years. CONCLUSIONS: Nutrition therapy based on patient-specific biophysical parameters helps to maintain body weight and induces a more optimal nutritional balance in cachectic cancer patients. Moreover, survival in cancer patients improved when their nutritional status, even partially, ameliorated.

Nutritional and metabolic alterations during continuous renal replacement therapy.

Adequate feeding of critically ill patients under continuous renal replacement therapy (CRRT) remains a challenging issue. We performed a systematic search of the literature published between 1992 and 2012 using the quorum guidelines regarding nutrition in intensive care unit patients treated with CRRT. Daily recommended energy requirements during CRRT are between 25 and 35 kcal/kg with carbohydrates and lipids accounting for 60-70% and 30-40% of calorie intake, respectively. Daily protein needs range from 1.5 to 1.8 g/kg. Indirect calorimetry corrected for CRRT-induced CO2 diversion should be used to more correctly match calorie intake to the real needs. This type of tool is not yet available but hopefully soon. Electrolyte deficit as well as overload have been described during CRRT but, in general, can be easily controlled. Although not strongly evidenced, consensus exists to supplement important micronutrients such as amino acids (glutamine), water-soluble vitamins and trace elements.

Hemodialysis in chronic kidney disease--balancing fluid and salt on the inflammation tightrope.

Haemodialysis (HD) is a well-established, longstanding, and life-saving treatment for patients with chronic kidney disease (CKD) or acute kidney injury (AKI). However, side-effects of HD in CKD patients are numerous and remain problematic. Amongst others, CKD patients are susceptible to short-term effects caused by abnormalities in water and electrolyte balance and long-term effects related to sustained inflammation short-term side-effects of HD such as errors in sodium content of dialysate could readily be overcome by correct baseline labelling of dialysates and the ongoing rigorous implementation of safety procedures by staff nurses and physicians. The proper implementation of biofeedback systems, with tight safety alarm limits and conductivity based detection systems including the analysis of ionic mass balance could have prevented the shortfalls described. Long-term untoward effects of HD are mainly due to sustained inflammation and are correlated with higher morbidity and mortality. Unfortunately, the pathophysiologic mechanisms that underpin the inflammatory processes induced by HD remain poorly understood or incompletely unravelled. Within the wide array of inflammatory (inter)actions, cytokines are undoubtedly key players but interesting biomarkers (e.g. follistatin) and pathways (e.g. erythropoietin hyporesponsiveness) have come into play. Therapeutic interventions in differing fields such as vascular access, avoidance of intra-dialytic hypotension and pharmacologic interventions with statins, angiotensin II receptor antagonists or vitamine D supplementation may be of significance. However, confirmatory trials investigating of all these promising therapies are, as yet, lacking. The impact of the dialysis technique itself should not be underestimated.

Feasibility of cerebral magnetic resonance imaging in patients with externalised spinal cord stimulator.

OBJECT: Spinal cord stimulation (SCS) is a well-known treatment option for intractable neuropathic pain after spinal surgery, but its pathophysiological mechanisms are poorly stated. The goal of this study is to analyse the feasibility of using brain MRI, functional MRI (fMRI) and Magnetic Resonance Spectroscopy (MRS) as tools to analyse these mechanisms in patients with externalised neurostimulators during trial period. METHODS: The authors conducted in an in vitro and in vivo study analysing safety issues when performing brain MRI, fMRI and MRS investigations in human subjects with externalised SCS. Temperature measurements in vitro were performed simulating SCS during MRI sequences using head transmit-receive coils in 1.5 and 3 T MRI systems. 40 Patients with externalised SCS were included in the in vivo study. 20 patients underwent brain MRI, fMRI and another 20 patients underwent brain MRI and MRS. RESULTS: A maximal temperature increase of 0.2°C was measured and neither electrode displacements nor hardware failures were observed. None of the patients undergoing the MRS sequences at the 1.5 or 3 T MRI scanners described any discomfort or unusual sensations. CONCLUSION: We can conclude that brain MRI, fMRI and MRS studies performed in patients with externalised SCS can be safely executed.

Retrograde C0-C1 insertion of cervical plate electrode for chronic intractable neck and arm pain.

OBJECTIVE: Spinal cord stimulation is an effective treatment for chronic neuropathic pain after spinal surgery. In addition to the most common placement of electrodes at the thoracic level for low back and leg pain, electrodes can also be placed on a cervical level in patients with chronic neck and upper limb pain. Surgical insertion of plate electrodes via an orthodromal direction requires a partial laminectomy. Therefore, the authors describe a surgical technique using retrograde insertion of a plate electrode to avoid laminectomy. METHODS: Six patients with uncontrolled neck and upper limb pain despite optimal analgesic medication were treated with a surgical electrode placed at the C1-C2 level via a retrograde placement technique without laminectomy. RESULTS: All patients received stimulation paresthesias at the desired regions and reported significant pain reduction in the neck and arm regions. CONCLUSION: This retrograde placement of plate electrodes enables cervical lordosis to be overcome and results in adequate stimulation of the upper cervical region, which is mandatory to reduce neck and shoulder pain without laminectomy.

Pharmacokinetics of a loading dose of amikacin in septic patients undergoing continuous renal replacement therapy.

Data on the optimal amikacin regimen during continuous renal replacement therapy (CRRT) are scarce and the proposed loading dose of 10mg/kg may result in inadequate drug levels. The aim of this study was to describe the pharmacokinetics of a 25 mg/kg first dose of amikacin in septic shock patients treated with CRRT. Serum samples were collected before (t=0 h) and at 1 (peak), 1.5, 4.5, 8 and 24 h after a 30-min amikacin infusion in 13 consecutive patients treated with a combination of amikacin and ß-lactam. Blood amikacin levels were measured using a validated fluorescence polarisation immunoassay method. In 9 patients (69%) the peak concentration was >64 mg/L, which corresponds to eight times the minimal inhibitory concentration breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) for Enterobacteriaceae and Pseudomonas aeruginosa (susceptible <8 mg/L, resistant >16 mg/L). The median (range) total volume of distribution was 0.50 L/kg (0.22-4.05 L/kg), the elimination half-life was 6.5h (4.5-279.6h) and total drug clearance (CL) was 1.26 mL/min/kg (0.1-3.30 mL/min/kg). Only three patients had drug concentrations at 24h (C(min)) of <5mg/L and the median predicted time needed to reach this value was 34 h (14-76 h). There was no correlation between CRRT parameters and C(min), CL or the time to C(min)<5mg/L. In septic shock patients treated with CRRT, a first dose of ≥ 25 mg/kg amikacin is therefore required to reach therapeutic peak concentrations. However, as drug clearance is reduced, amikacin concentrations remained above the threshold of renal toxicity at 24h. The therapeutic benefit of high-dose aminoglycoside therapy should be balanced with its potential renal effects in septic patients receiving CRRT.

Insufficient ß-lactam concentrations in the early phase of severe sepsis and septic shock.

INTRODUCTION: Altered pharmacokinetics (PK) in critically ill patients can result in insufficient serum ß-lactam concentrations when standard dosages are administered. Previous studies on ß-lactam PK have generally excluded the most severely ill patients, or were conducted during the steady-state period of treatment. The aim of our study was to determine whether the first dose of piperacillin-tazobactam, ceftazidime, cefepime, and meropenem would result in adequate serum drug concentrations in patients with severe sepsis and septic shock. METHODS: Open, prospective, multicenter study in four Belgian intensive care units. All consecutive patients with a diagnosis of severe sepsis or septic shock, in whom treatment with the study drugs was indicated, were included. Serum concentrations of the antibiotics were determined by high-pressure liquid chromatography (HPLC) before and 1, 1.5, 4.5 and 6 or 8 hours after administration. RESULTS: 80 patients were treated with piperacillin-tazobactam (n = 27), ceftazidime (n = 18), cefepime (n = 19) or meropenem (n = 16). Serum concentrations remained above 4 times the minimal inhibitory concentration (T > 4 × MIC), corresponding to the clinical breakpoint for Pseudomonas aeruginosa defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST), for 57% of the dosage interval for meropenem (target MIC = 8 µg/mL), 45% for ceftazidime (MIC = 32 µg/mL), 34% for cefepime (MIC = 32 µg/mL), and 33% for piperacillin-tazobactam (MIC = 64 µg/mL). The number of patients who attained the target PK profile was 12/16 for meropenem (75%), 5/18 for ceftazidime (28%), 3/19 (16%) for cefepime, and 12/27 (44%) for piperacillin-tazobactam. CONCLUSIONS: Serum concentrations of the antibiotic after the first dose were acceptable only for meropenem. Standard dosage regimens for piperacillin-tazobactam, ceftazidime and cefepime may, therefore, be insufficient to empirically cover less susceptible pathogens in the early phase of severe sepsis and septic shock.