Enrico Fiaccadori

ESPEN Guidelines on Parenteral Nutrition: adult renal failure.

Among patients with renal failure, those with ARF and critical illness represent by far the largest group undergoing artificial nutrition. ARF, especially in the ICU, seldom occurs as isolated organ failure but rather is a component of a much more complex metabolic environment, in the setting of the multiple organ failure. Nutritional programs for ARF patients must consider not only the metabolic derangements peculiar to renal failure and with the underlying disease process/associated complications, but also the relevant derangements in nutrient balance due to renal replacement therapies, especially when highly efficient renal replacement therapies (RRT) are used, such as continuous veno-venous hemofiltration (CVVH), or prolonged intermittent modalities such as sustained low-efficiency dialysis (SLED). Finally it is to be taken into account that nutrient requirements can change considerably during the course of illness itself (see also guidelines on PN in intensive care). From a metabolic point of view, patients with CKD or on chronic HD who develop a superimposed acute illness should be considered to be similar to patients with ARF. The same principles in respect of PN should therefore be applied.

Myocardial depression in sepsis: From pathogenesis to clinical manifestations and treatment

The cardiovascular system plays a key role in sepsis, and septic myocardial depression is a common finding associated with increased morbidity and mortality. Myocardial depression during sepsis is not clearly defined, but it can perhaps be best described as a global (systolic and diastolic) dysfunction of both the left and right sides of the heart. The pathogenesis of septic myocardial depression involves a complex mix of systemic (hemodynamic) factors and genetic, molecular, metabolic, and structural alterations. Pulmonary artery catheterization and modern echo-Doppler techniques are important diagnostic tools in this setting. There are no specific therapies for septic myocardial depression, and the cornerstone of management is control of the underlying infectious process (adequate antibiotic therapy, removal of the source) and hemodynamic stabilization (fluids, vasopressor and inotropic agents). In this review, we will summarize the pathogenesis, diagnosis, and treatment of myocardial depression in sepsis. Additional studies are needed in order to improve diagnosis and identify therapeutic targets in septic myocardial dysfunction.

Severe Hypomagnesemia During Long-term Treatment With a Proton Pump Inhibitor

Severe hypomagnesemia is a serious clinical ondition that can be complicated by lifehreatening arrhythmias (ventricular tachycardia, entricular fibrillation, and torsades de pointes) nd neurologic manifestations (neuromuscular yperexcitability, frank ataxia, confusion, deirium, and seizures). Moreover, hypokalemia nd hypocalcemia frequently are documented as ccompanying electrolyte disorders. Hypomagesemia is relatively common in hospitalized atients, particularly in intensive care units. eading causes of the acquired disorder are malbsorption, uncontrolled diabetes, chemotherapy, cute pancreatitis, drugs, and refeeding. Very few cases of severe hypomagnesemia elated to long-term use of proton pump inhibiors (PPIs) have been published to date, and he likely pathogenetic mechanisms are not fully lucidated. We report a case of severe symptomatic hypoagnesemia in a patient treated with PPIs for any years because of Barrett esophagus. The ifferential diagnosis and potential pathogenetic echanisms are discussed within a more general onceptual framework of the pathophysiology tate of serum magnesium homeostasis.

Alterations of intestinal barrier and microbiota in chronic kidney disease

Recent studies have highlighted the close relationship between the kidney and the gastrointestinal (GI) tract--frequently referred to as the kidney--gut axis--in patients with chronic kidney disease (CKD). In this regard, two important pathophysiological concepts have evolved: (i) production and accumulation of toxic end-products derived from increased bacterial fermentation of protein and other nitrogen-containing substances in the GI tract, (ii) translocation of endotoxins and live bacteria from gut lumen into the bloodstream, due to damage of the intestinal epithelial barrier and quantitative/qualitative alterations of the intestinal microbiota associated with the uraemic milieu. In both cases, these gut-centred alterations may have relevant systemic consequences in CKD patients, since they are able to trigger chronic inflammation, increase cardiovascular risk and worsen uraemic toxicity. The present review is thus focused on the kidney-gut axis in CKD, with special attention to the alterations of the intestinal barrier and the local microbiota (i.e. the collection of microorganisms living in a symbiotic coexistence with their host in the intestinal lumen) and their relationships to inflammation and uraemic toxicity in CKD. Moreover, we will summarize the most important clinical data suggesting the potential for nutritional modulation of gut-related inflammation and intestinal production of noxious by-products contributing to uraemic toxicity in CKD patients.

The relation between the incidence of hypernatremia and mortality in patients with severe traumatic brain injury

IntroductionThe study was aimed at verifying whether the occurrence of hypernatremia during the intensive care unit (ICU) stay increases the risk of death in patients with severe traumatic brain injury (TBI). We performed a retrospective study on a prospectively collected database including all patients consecutively admitted over a 3-year period with a diagnosis of TBI (post-resuscitation Glasgow Coma Score ≤ 8) to a general/neurotrauma ICU of a university hospital, providing critical care services in a catchment area of about 1,200,000 inhabitants.MethodsDemographic, clinical, and ICU laboratory data were prospectively collected; serum sodium was assessed an average of three times per day. Hypernatremia was defined as two daily values of serum sodium above 145 mmol/l. The major outcome was death in the ICU after 14 days. Cox proportional-hazards regression models were used, with time-dependent variates designed to reflect exposure over time during the ICU stay: hypernatremia, desmopressin acetate (DDAVP) administration as a surrogate marker for the presence of central diabetes insipidus, and urinary output. The same models were adjusted for potential confounding factors.ResultsWe included in the study 130 TBI patients (mean age 52 years (standard deviation 23); males 74%; median Glasgow Coma Score 3 (range 3 to 8); mean Simplified Acute Physiology Score II 50 (standard deviation 15)); all were mechanically ventilated; 35 (26.9%) died within 14 days after ICU admission. Hypernatremia was detected in 51.5% of the patients and in 15.9% of the 1,103 patient-day ICU follow-up. In most instances hypernatremia was mild (mean 150 mmol/l, interquartile range 148 to 152). The occurrence of hypernatremia was highest (P = 0.003) in patients with suspected central diabetes insipidus (25/130, 19.2%), a condition that was associated with increased severity of brain injury and ICU mortality. After adjustment for the baseline risk, the incidence of hypernatremia over the course of the ICU stay was significantly related with increased mortality (hazard ratio 3.00 (95% confidence interval: 1.34 to 6.51; P = 0.003)). However, DDAVP use modified this relation (P = 0.06), hypernatremia providing no additional prognostic information in the instances of suspected central diabetes insipidus.ConclusionsMild hypernatremia is associated with an increased risk of death in patients with severe TBI. In a proportion of the patients the association between hypernatremia and death is accounted for by the presence of central diabetes insipidus.

Copeptin (CTproAVP), a new tool for understanding the role of vasopressin in pathophysiology

Abstract Arginine vasopressin (AVP) plays a key role in many physiologic and pathologic processes. The most important stimulus for AVP release is a change in plasma osmolality. AVP is also involved in the response and adaptation to stress. Reliable measurement of AVP is hindered by several factors. Over 90% of AVP is tightly bound to platelets, and its estimation is influenced by the number of platelets, incomplete removal of platelets or pre-analytical processing steps. Copeptin (CTproAVP), a 39-aminoacid glycopeptide, is a C-terminal part of the precursor pre-provasopressin (pre-proAVP). Activation of the AVP system stimulates CTproAVP secretion into the circulation from the posterior pituitary gland in equimolar amounts with AVP. Therefore CTproAVP directly reflects AVP concentration and can be used as a surrogate biomarker of AVP secretion. In many studies CTproAVP represents AVP levels and its behavior represents changes in plasma osmolality, stress and various disease states, and shows some of the various physiologic and pathophysiologic conditions associated with increased or decreased AVP. Increased CTproAVP concentration is described in several studies as a strong predictor of mortality in patients with chronic heart failure and acute heart failure. Autosomal polycystic kidney disease (ADPKD) patients have both central and nephrogenic defects in osmoregulation and CTproAVP balance. A possibility raised by these clinical observations is that CTproAVP may serve to identify patients who could benefit from an intervention aimed at countering AVP.

Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

Hemorrhagic complications have been reported in up to 30% of critically ill patients with AKI undergoing RRT with systemic anticoagulation. Because bleeding is associated with significantly increased mortality risk, strategies aimed at reducing hemorrhagic complications while maintaining extracorporeal circulation should be implemented. Among the alternatives to systemic anticoagulation, regional citrate anticoagulation has been shown to prolong circuit life while reducing the incidence of hemorrhagic complications and lowering transfusion needs. For these reasons, the recently published Kidney Disease Improving Global Outcomes Clinical Practice Guidelines for Acute Kidney Injury have recommended regional citrate anticoagulation as the preferred anticoagulation modality for continuous RRT in critically ill patients in whom it is not contraindicated. However, the use of regional citrate anticoagulation is still limited because of concerns related to the risk of metabolic complications, the complexity of the proposed protocols, and the need for customized solutions. The introduction of simplified anticoagulation protocols based on citrate and the development of dialysis monitors with integrated infusion systems and dedicated software could lead to the wider use of regional citrate anticoagulation in upcoming years.

The Relationship Between Blood Pressure and Pain

The relationship between pain and hypertension is potentially of great pathophysiological and clinical interest, but is poorly understood. The perception of acute pain initially plays an adaptive role, which results in the prevention of tissue damage. The consequence of ascending nociception is the recruitment of segmental spinal reflexes through the physiological neuronal connections. In proportion to the magnitude and duration of the stimulus, these spinal reflexes cause the activation of the sympathetic nervous system, which increases peripheral resistances, heart rate, and stroke volume. The response also involves the neuroendocrine system, and, in particular, the hypothalamic‐pituitary‐adrenal axis, in addition to further activation of the sympathetic system by adrenal glands. However, in proportion to an elevation in resting blood pressure, there is a contemporary and progressive reduction in sensitivity to acute pain, which could result in a tendency to restore arousal levels in the presence of painful stimuli. The pathophysiological pattern is significantly different in the setting of chronic pain, in which the adaptive relationship between blood pressure and pain sensitivity is substantially reversed. The connection between acute or chronic pain and cardiovascular changes is supported observationally, but some of this indirect evidence is confirmed by experimental models and human studies. The pain regulatory process and functional interaction between cardiovascular and pain regulatory systems are briefly reviewed. Various data obtained are described, together with their potential clinical implications.

Mortality rate comparison after switching from continuous to prolonged intermittent renal replacement for acute kidney injury in three intensive care units from different countries

BACKGROUND Prolonged intermittent renal replacement therapy (PIRRT) is a dialysis modality for critically ill patients that in theory combines the superior detoxification and haemodynamic stability of the continuous renal replacement therapy (CRRT) with the operational convenience, reduced haemorrhagic risk and low cost of conventional intermittent haemodialysis. However, the extent to which PIRRT should replace these other modalities is uncertain because comparative studies of mortality are lacking. We retrospectively examined the mortality data from three general intensive care units (ICUs) in different countries that have switched their predominant therapeutic approach from CRRT to PIRRT. We assessed whether this practice change was associated with a change in mortality rate. METHODS Data were analysed from ICUs in New Zealand, Australia and Italy. The study population comprised all patients requiring renal replacement therapy from 1 January 1995 to 31 December 2005 (n = 1347), the period of time spanning the change from CRRT to PIRRT in each unit. Poisson regression models were used to estimate the incident rate ratio (IRR) for death, comparing the periods before and after change to PIRRT in each unit. Estimates were adjusted for patient illness severity (APACHE II score) and for the underlying time trend in mortality rate over time. RESULTS The change from CRRT to PIRRT was not associated with any increase in mortality rate, with an adjusted IRR of 1.02 (0.61-1.71). The IRR was virtually identical in the three ICUs (P-value = 0.63 for the difference in the IRR between ICUs). CONCLUSIONS Switching from CRRT to PIRRT was not associated with a change in mortality rate. Pending the results of a randomized trial, our study provides evidence that PIRRT might be equivalent to CRRT in the general ICU patient.

Nutritional assessment and delivery in renal replacement therapy patients.

The present review is aimed at illustrating and discussing literature data and recent guidelines concerning artificial nutrition in patients with acute kidney injury (AKI) on renal replacement therapy (RRT). Protein‐energy wasting often complicates the clinical course of AKI in critically ill patients, increasing their morbidity and mortality risk. The most severe forms of the syndrome – those observed in ICU patients – are characterized by hypercatabolism with relevant lean body mass loss. In this clinical condition, artificial nutrition (enteral and/or parenteral nutrition) is considered an integral part of the complex therapeutic approach. Even though many issues concerning nutrition in AKI are common to other critically ill patients, the presence of AKI with the ensuing impairment of the kidney homeostatic function introduces specific problems and can make more difficult to give the patient an adequate nutrient provision. Thus, peculiarities of the syndrome – and of RRT itself – must be taken into account in nutritional planning for these patients. Recent guidelines have suggested that the enteral route should be the preferred one, even though parenteral nutrition is often required to target nutritional needs (25–30 kcal/kg body weight/day, and 1.5 + 0.2 g/kg/day to compensate for amino acid losses during RRT). Special attention should be paid to the impact of different forms of RRT on the possible loss of both macro‐ and micronutrients and vitamins, as well as to the risk of metabolic complications. Finally, close integration between nutritional support and RRT is required, aiming at carefully tailoring both therapies on patient’s changing needs.