Gil Hardy

Thiamine supplementation in the critically ill.

Purpose of reviewTo summarize the properties of thiamine and evaluate current evidence on thiamine status and supplementation, for different populations of critically ill patients. Recent findingsThiamine, in the form of thiamine pyrophosphate, is a critical co-factor in the glyocolysis and oxidative decarboxylation of carbohydrates for energy production. Different studies have shown that critical illness in adults and children is characterized by absolute or relative thiamine depletion, which is associated with an almost 50% increase in mortality. Thiamine deficiency should be suspected in different clinical scenarios such as severe sepsis, burns, unexplained heart failure or lactic acidosis, neurological disorder in patients with previous history of alcoholism, starvation, chronic malnutrition, long-term parenteral feeding, hyperemesis gravidarum, or bariatric surgery. Nonetheless, thiamine supplements are not routinely given to critically ill patients. Clinicians should be able to suspect and recognize risk factors for the occurrence of severe neurological disorders secondary to thiamine deficiency, as early treatment can prevent the appearance of permanent neurological damage. SummarySymptoms and signs associated with thiamine deficiency lack sensitivity and specificity in critically ill patients. Consequently, depletion is frequently unrecognized and underdiagnosed by clinicians. Potentially deleterious consequences of thiamine depletion should be avoided by early and appropriate supplementation.

Manganese in parenteral nutrition: who, when, and why should we supplement?

Micronutrient requirements are not fully understood. Parenteral nutrition (PN) usually contains the trace element (TE) manganese (Mn) from fixed-concentration TE supplements. Multiple TE formulations may not be optimal in pediatric and home PN. Moreover, most PN products contain Mn as a ubiquitous contaminant. Excessive Mn can lead to Parkinson-like symptoms resulting from hypermanganesemia. A survey of 40 Australasian hospitals that contributed data on 108 patients to the annual home PN register and a systematic review of the literature were conducted to establish the scope of the potential problem of Mn toxicity in PN patients. Exposure to Mn doses 5-6 times current daily requirements, together with the TE contamination that is reported in PN products, can lead to neurotoxicity. Whole-blood levels are more accurate for monitoring and correlate well with signal intensity of magnetic resonance imaging. Current TE formulations restrict prescribing options. The regulatory mechanisms of Mn homeostasis are bypassed via the parenteral route so elimination via the hepatobiliary system is impaired, resulting in tissue or brain accumulation. Published dosage recommendations may be excessive and official guidelines require revision. Variability in clinical practices necessitates that individual TE additives are more widely available and multiple TE products reformulated. More frequent monitoring for any brain accumulation is recommended. The scarcity of PN-associated Mn deficiency, plus the growing evidence for Mn toxicity, leads to the conclusion that it is unnecessary for Mn to be prescribed routinely for pediatric or long-term PN patients.

Selenium Supplementation in the Critically Ill

Selenium (Se) is an essential trace element with antioxidant, immunological, and anti-inflammatory properties, which are attributed to its presence in selenoproteins, as the 21st amino acid selenocysteine. These selenoenzymes are involved in redox signaling, antioxidant defense, thyroid hormone metabolism, and immune responses. Dietary intakes differ considerably between geographical regions, due to variability of the Se food content, leading to differences in dietary reference intakes and toxicity cautions. Critical illness with systemic inflammatory response syndrome (SIRS) is characterized by Se depletion with high morbidity and mortality. Se status correlates well with clinical outcome in SIRS and may be useful as an early predictor of survival. Several investigators have evaluated the benefits of Se supplementation for the critically ill, either as monotherapy or in an antioxidant micronutrient combination. Pharmaconutrition, with high-dose Se (from 500-1600 µg/d) involving an initial loading bolus, followed by continuous infusion, appears to be safe and efficacious, with evidence that it can improve clinical outcome by reducing illness severity, infectious complications, and decreasing mortality in the intensive care unit (ICU). We now have a clearer understanding of the pharmacokinetics of the initial and transient pro-oxidant effect of an intravenous bolus of selenite and the antioxidant effect of continuous infusion. Better biomarkers to ascertain optimum Se requirements for individual patients are now needed, and clinical practice guidelines need improvement. Nevertheless, sufficient evidence is available to consider initiating high-dose intravenous Se therapy routinely in critically ill SIRS patients, immediately on admission to the ICU.

Selenium and Its Supplementation in Cardiovascular Disease—What do We Know?

The trace element selenium is of high importance for many of the body’s regulatory and metabolic functions. Balanced selenium levels are essential, whereas dysregulation can cause harm. A rapidly increasing number of studies characterizes the wide range of selenium dependent functions in the human body and elucidates the complex and multiple physiological and pathophysiological interactions of selenium and selenoproteins. For the majority of selenium dependent enzymes, several biological functions have already been identified, like regulation of the inflammatory response, antioxidant properties and the proliferation/differentiation of immune cells. Although the potential role of selenium in the development and progression of cardiovascular disease has been investigated for decades, both observational and interventional studies of selenium supplementation remain inconclusive and are considered in this review. This review covers current knowledge of the role of selenium and selenoproteins in the human body and its functional role in the cardiovascular system. The relationships between selenium intake/status and various health outcomes, in particular cardiomyopathy, myocardial ischemia/infarction and reperfusion injury are reviewed. We describe, in depth, selenium as a biomarker in coronary heart disease and highlight the significance of selenium supplementation for patients undergoing cardiac surgery.

Borage oil in the treatment of atopic dermatitis

Nutritional supplementation with omega-6 essential fatty acids (omega-6 EFAs) is of potential interest in the treatment of atopic dermatitis. EFAs play a vital role in skin structure and physiology. EFA deficiency replicates the symptoms of atopic dermatitis, and patients with atopic dermatitis have been reported to have imbalances in EFA levels. Although direct proof is lacking, it has been hypothesized that patients with atopic dermatitis have impaired activity of the delta-6 desaturase enzyme, affecting metabolism of linoleic acid to gamma-linolenic acid (GLA). However, to date, studies of EFA supplementation in atopic dermatitis, most commonly using evening primrose oil, have produced conflicting results. Borage oil is of interest because it contains two to three times more GLA than evening primrose oil. This review identified 12 clinical trials of oral or topical borage oil for treatment of atopic dermatitis and one preventive trial. All studies were controlled and most were randomized and double-blind, but many were small and had other methodological limitations. The results of studies of borage oil for the treatment of atopic dermatitis were highly variable, with the effect reported to be significant in five studies, insignificant in five studies, and mixed in two studies. Borage oil given to at-risk neonates did not prevent development of atopic dermatitis. However, the majority of studies showed at least a small degree of efficacy or were not able to exclude the possibility that the oil produces a small benefit. Overall, the data suggest that nutritional supplementation with borage oil is unlikely to have a major clinical effect but may be useful in some individual patients with less severe atopic dermatitis who are seeking an alternative treatment. Which patients are likely to respond cannot yet be identified. Borage oil is well tolerated in the short term but no long-term tolerability data are available.

Is manganese an essential supplement for parenteral nutrition

Purpose of reviewTo summarize the role of the essential trace element, manganese, its potential toxicity, monitoring methods and dosage recommendations for nutrition support. Recent findingsParenteral nutrition usually contains manganese as part of a fixed concentration multiple trace element supplement. Recent literature identifies potential problems in this approach and reports toxic symptoms resulting from hypermanganesaemia in paediatric and long-term home patients. Elimination by the hepatobiliary system is frequently impaired, and parenteral administration bypasses the regulatory mechanisms of homeostasis. Together with occasional oral intake and product contamination, this can lead to brain accumulation and neurotoxicity, with individual responses to supplementation difficult to predict. Regular monitoring is recommended, but plasma and serum analyses are poor indicators of body stores. Whole blood concentrations are more accurate and correlate with signal intensity of MRI. We have identified a need for individual trace element additives to be more widely available and for multitrace element products to be reformulated. There is now a persuasive argument for not routinely adding manganese to parenteral nutrition admixtures. SummaryHigh intravenous doses of manganese can lead to neurotoxicity. Current dosage guidelines and trace element formulations need revision. Frequent monitoring to identify tissue accumulation is recommended for paediatric and long-term home parenteral nutrition patients.

Selenium supplementation in the critically ill: posology and pharmacokinetics

Purpose of reviewTo analyze current evidence for the posology and pharmacokinetics of selenium supplementation in the critically ill. Recent findingsAntioxidants and especially high-dose parenteral selenium may be associated with a significant reduction in mortality among critically ill patients with systemic inflammatory response syndrome (SIRS). Selenium seems to be a cornerstone of the antioxidant defense in SIRS patients. In the past few years, several clinical studies have evaluated the effect of selenium (as sodium selenite) in monotherapy or as part of a multimicronutrient approach, on relevant end points for the critically ill. However, the results from these studies have sometimes been contradictory. We now have a better understanding of the pharmacokinetics of the transient prooxidant effect of an intravenous (i.v.) bolus followed by the antioxidant effect of continuous infusion, which seems efficacious and well tolerated. Clinical confirmation of the potentially advantageous synergism between selenium and glutamine may soon be forthcoming, but the most appropriate and the optimum time of supplementation remains undetermined. SummaryThis review summarizes current knowledge on selenium supplementation in the critically ill. High-dose i.v. selenite as a bolus injection plus continuous infusion appears well tolerated and optimizes selenium plasma levels and antioxidant selenoenzymes activities. Additional investigations into the posology and pharmacokinetic profile of selenium are still required. Further studies should aim to demonstrate a definitive benefit of i.v. selenite, alone or in combination, on antioxidant capacity and mortality in the critically ill.

AuSPEN clinical practice guideline for home parenteral nutrition patients in Australia and New Zealand

OBJECTIVE Evidence based guidelines for home parenteral nutrition (HPN) were commissioned by the Australasian Society of Parenteral and Enteral Nutrition (AuSPEN) and developed by a multidisciplinary group. The guidelines make recommendations in four domains: patient selection, patient training, formulation and monitoring regimens, and preventing and managing complications. METHODS The Appraisal of Guidelines Research and Evaluation guideline process was used to focus questions and identify evidence by systematic literature reviews of meta-analyses and randomized control trials in the Cochrane Library, Medline, Embase, and Cinahl to mid-2007. Where no randomized control trial evidence was found, the search was broadened to observational studies and expert opinion from related national and international guidelines as assessed by a validated appraisal process. RESULTS Selection of patients must assess individual risk/benefit and medical ethics. Patient training should be undertaken within a structured framework. Access devices should be selected for lowest risk of complications, including occlusion, sepsis, and breakage and be managed by early diagnosis and treatment. HPN should be formulated according to individual patient requirements by professionals with relevant skills and training. Pumps and ancillary products should conform to quality standards. Other intravenous medications may be prescribed provided these are reviewed for compatibility and effects on metabolic status. CONCLUSION Overall there is a lack of randomized control trials to provide high-quality evidence-based guidance but graded recommendations can be made. Multidisciplinary teams in centers with HPN management expertise are required for optimal care. This guideline should improve outcomes and quality of life for HPN patients in Australia and New Zealand.

Practical implications of nutritional support during continuous renal replacement therapy.

Continuous blood membrane interactions during continuous renal replacement therapy cause bioincompatibility and low grade inflammatory reactions with potentially adverse consequences on protein metabolism and immunocompetence. In designing a nutritional program for patients receiving this treatment, these adverse metabolic effects, especially the loss of nutritional substrates, must be considered. This review provides a practical overview of nutritional support in acute renal failure, including assessment techniques, determination of nutrient needs, and appropriate intervention for patient support.

High-dose selenium for critically ill patients with systemic inflammation: Pharmacokinetics and pharmacodynamics of selenious acid: A pilot study

OBJECTIVE Systemic inflammatory response syndrome is characterized by increased urinary excretion of selenium and low serum concentration. Repletion by parenteral selenite is the most efficacious form of supplementation. However, the optimum safe dose and mode of administration remain controversial. We aimed to determine pharmacokinetic and pharmacodynamic profiles of selenite and estimate a safe dose to optimize selenium status. METHODS A prospective, randomized, pilot study in 20 patients with systemic inflammatory response syndrome compared a high-dose (HD) group that received a loading dose of selenium as selenite 15.18 micromol over 2 h and thereafter 10.12 micromol/d as a continuous intravenous infusion (CIV) for 10 d with a very-high-dose (VHD) group that received a loading dose of 25.30 micromol over 2 h and thereafter 20.24 micromol as a CIV for 10 d. Clinical outcome was evaluated by length of stay in the intensive care unit, incidence of ventilator-associated pneumonia, and Sequential Organ Failure Assessment score. RESULTS Patients in group HD (n = 10, age 54 +/- 23 y) had an Acute Physiology and Chronic Health Evaluation II score of 23 +/- 5 and a Sequential Organ Function Assessment score of 10 +/- 2. Those in group VHD (n = 10, age 41 +/- 19 y) had scores of 21 +/- 7 and 8 +/- 3, respectively. Pharmacokinetic concentration/time curves for serum selenium overlapped but were independent of dose, whereas the pharmacodynamics were different, showing maximum glutathione peroxidase activity only with VHD. Glutathione peroxidase decreased after day 7 independently of the selenium dose. Clinical outcomes were similar in both groups. CONCLUSION A bolus loading dose of selenite providing 2000 microg of selenium (25.30 micromol) followed by a CIV of 1600 microg/d (20.24 micromol/d) for 10 d is most effective at returning serum selenium to physiologic levels and safely maximizing glutathione peroxidase activity.