Ammonia and nutritional therapy in the critically ill: when to worry, when to test and how to treat?

PURPOSE OF REVIEW: Hyperammonaemia is almost always develops in patients with severe liver failure and this remains the commonest cause of elevated ammonia concentrations in the ICU. Nonhepatic hyperammonaemia in ICU presents diagnostic and management challenges for treating clinicians. Nutritional and metabolic factors play an important role in the cause and management of these complex disorders. RECENT FINDINGS: Nonhepatic hyperammonaemia causes such as drugs, infection and inborn errors of metabolism may be unfamiliar to clinicians and risk being overlooked. Although cirrhotic patients may tolerate marked elevations in ammonia, other causes of acute severe hyperammonaemia may result in fatal cerebral oedema. Any coma of unclear cause should prompt urgent measurement of ammonia and severe elevations warrant immediate protective measures as well as treatments such as renal replacement therapy to avoid life-threatening neurological injury. SUMMARY: The current review explores important clinical considerations, the approach to testing and key treatment principles that may prevent progressive neurological damage and improve outcomes for patients with hyperammonaemia, especially from nonhepatic causes.

Liquorice Intoxication Can Lead to Cardiac Arrest!

A 45-year-old man was admitted to the Emergency Department with fatigue and muscular weakness. Soon after hospital admission, he developed "torsades de pointe" and was successfully resuscitated. The admission laboratory investigations had revealed a profound hypokalemia (1.65 mmol/L). The patient had a long-term use of alcohol-free "pastis" in an attempt to reduce his chronic ethanol consumption. As the beverage likely contained a significant amount of liquorice, the diagnosis of glycyrrhizin chronic intoxication was suspected. The diagnosis of liquorice-related pseudohyperaldosteronism was assessed by normal plasma aldosterone levels and low plasma renin activity. Intravenous and oral supplementation of potassium was required for 5 days, and the patient had an uneventful follow-up.

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.

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.

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.