MECCIAS trial: Metabolic consequences of continuous veno-venous hemofiltration on indirect calorimetry.

BACKGROUND: and aims: Caloric prescription based on resting energy expenditure (REE) measured with indirect calorimetry (IC) improves outcome and is the gold standard in nutritional therapy of critically ill patients. Until now continuous renal replacement therapy (CRRT) precluded the use of IC due to several mechanisms. We investigated the impact of CRRT on V̇CO2, V̇O2 and REE to facilitate indirect calorimetry during CRRT. METHODS: In 10 critically ill ventilated patient in need of continuous veno-venous hemofiltration (CVVH) using citrate predilution we performed IC in 4 different states: baseline, high dose, baseline with NaCl predilution and without CVVH. CO2 content of effluent fluid was measured by a point of care blood gas analyzer. Carbon dioxide production (V̇CO2) measured with IC was adapted by adding the CO2 flow of effluent and deducing CO2 flow in postdilution fluid to calculate a true V̇CO2. True REE was calculated with the Weir equation using the true V̇CO2. RESULTS: CO2 removal in effluent during baseline, high dose and NaCl predilution was respectively 24 mL/min, 38 mL/min and 23 mL/min. Together with the CO2 delivery by the postdilution fluid this led to an adaptation of REE respectively by 34 kcal/d or 2% (p = 0,002), 44 kcal/d or 3% (p = 0,002) and 33 kcal/d or 2% (p = 0,002). Compared to the true REE during baseline of 1935 ± 921 kcal/d, true REE during high dose was 1723 ± 752 kcal/d (p = 0.65), during NaCl predilution it was 1604 ± 633 kcal/d (p = 0.014) and without CRRT it was 1713 ± 704 kcal/d (p = 0.193). CONCLUSIONS: CO2 alterations due to CVVH are clinically of no importance so no correction factor of REE is needed with or without CVVH. IC must be performed during CVVH as CVVH seems to alter metabolism. These changes may be mainly explained by the use of citrate predilution.

Energy expenditure and caloric targets during continuous renal replacement therapy under regional citrate anticoagulation. A viewpoint.

BACKGROUND: Indirect calorimetry (IC) is the gold standard for measuring energy expenditure in critically ill patients However, continuous renal replacement therapy (CRRT) is a formal contraindication for IC use. AIMS: To discuss specific issues that hamper or preclude an IC-based assessment of energy expenditure and correct caloric prescription in CRRT-treated patients. METHODS: Narrative review of current literature. RESULTS: Several relevant pitfalls for validation of IC during CRRT were identified. First, IC measures CO2 production (VCO2) and O2 consumption to calculate resting energy expenditure (REE) with the Weir equation. VCO2 measurements are influenced by CRRT because CO2 is exchanged during the blood purification process. CO2 exchange also depends on type of pre- and/or postdilution fluid(s). CO2 dissolves in different forms with dynamic but unpredictable impact on VCO2. Second, the effect of immunologic activation and heat loss on REE caused by extracorporeal circulation during CRRT is poorly documented. Third, caloric prescription should be adapted to CRRT-induced in- and efflux of different nutrients. Finally, citrate, which is the preferred anticoagulant for CRRT, is a caloric source that may influence IC measurements and REE. CONCLUSION: Better understanding of CRRT-related processes is needed to assess REE and provide individualized nutritional therapy in this condition.

Elderly versus nonelderly patients with invasive aspergillosis in the ICU: a comparison and risk factor analysis for mortality from the AspICU cohort.

Data regarding the epidemiology and diagnosis of invasive aspergillosis in the critically ill population are limited, with data regarding elderly patients (≥75 years old) even scarcer. We aimed to further compare the epidemiology, characteristics and outcome of elderly versus nonelderly critically ill patients with invasive aspergillosis (IA) Prospective, international, multicenter observational study (AspICU) including adult intensive care unit (ICU) patients, with a culture and/or direct examination and/or histopathological sample positive for Aspergillus spp. at any site. We compared clinical characteristics and outcome of IA in ICU patients using two different diagnostic algorithms. Elderly and nonelderly ICU patients with IA differed in a number of characteristics, including comorbidities, clinical features of the disease, mycology testing, and radiological findings. No difference regarding mortality was found. According to the clinical algorithm, elderly patients were more likely to be diagnosed with putative IA. Elderly patients had less diagnostic radiological findings and when these findings were present they were detected late in the disease course. The comparison between elderly survivors and nonsurvivors demonstrated differences in clinical characteristics of the disease, affected sites and supportive therapy needed. All patients who were diagnosed with proven IA died. Increased vigilance combined with active search for mycological laboratory evidence and radiological confirmation are necessary for the timely diagnosis of IA in the elderly patient subset. Although elderly state per se is not a particular risk factor for mortality, a high SOFA score and the decision not to administer antifungal therapy may have an impact on survival of elderly patients.

Measuring resting energy expenditure during extracorporeal membrane oxygenation: preliminary clinical experience with a proposed theoretical model.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with severe respiratory failure. Indirect calorimetry (IC) is a safe and non-invasive method for measuring resting energy expenditure (REE). No data exist on the use of IC in ECMO-treated patients as oxygen uptake and carbon dioxide elimination are divided between mechanical ventilation and the artificial lung. We report our preliminary clinical experience with a theoretical model that derives REE from IC measurements obtained separately on the ventilator and on the artificial lung. METHODS: A patient undergoing veno-venous ECMO for acute respiratory failure due to bilateral pneumonia was studied. The calorimeter was first connected to the ventilator and oxygen consumption (VO2 ) and carbon dioxide transport (VCO2 ) were measured until steady state was reached. Subsequently, the IC was connected to the membrane oxygenator and similar gas analysis was performed. VO2 and VCO2 values at the native and artificial lung were summed and incorporated in the Weir equation to obtain a REEcomposite . RESULTS: At the ventilator level, VO2 and VCO2 were 29.5 ml/min and 16 ml/min. VO2 and VCO2 at the artificial lung level were 213 ml/min and 187 ml/min. Based on these values, a REEcomposite of 1703 kcal/day was obtained. The Faisy-Fagon and Harris-Benedict equations calculated a REE of 1373 and 1563 kcal/day. CONCLUSION: We present IC-acquired gas analysis in ECMO patients. We propose to insert individually obtained IC measurements at the native and the artificial lung in the Weir equation for retrieving a measured REEcomposite .

Measured versus calculated resting energy expenditure in critically ill adult patients. Do mathematics match the gold standard?

BACKGROUND: Indirect calorimetry (IC) is considered to be the standard method for estimating energy requirements in intensive care unit (ICU) patients. Hence, most ICU clinicians still rely on various mathematical formulas to calculate caloric requirements in their patients. We assessed whether measurements obtained by IC reached agreement with the results of such commonly used equations. METHODS: Retrospective study in consecutively hospitalized patients in a mixed medico-surgical adult ICU. Resting energy expenditure (REE) was measured by IC in all patients as a standard procedure within our routine nutritional care planning and simultaneously calculated from 10 distinct predictive equations. IC was performed with the VmaxTM Encore 29n calorimeter (VIASYS Healthcare Inc, Yorba Linda, CA). Bland-Altman plots and regression analysis were used to assess agreement between measured and calculated REE. RESULTS: The study included 259 critically ill patients: 161 subjects (62%) met final analysis criteria (age 63 ± 16 years; 58% males). Measured REE was 1571 ± 423.5 kcal/24 h with VO2 0.23 ± 0.06 L/min and VCO2 0.18 ± 0.05 L/min. Calculated values correlated very weakly with IC-derived measurements. Only the Swinamer equation and the Penn State 2010 reached an R² > 0.5. Widely used formulas in daily ICU practice such as the adjusted Harris Benedict, Faisy-Fagon, and ESICM '98 statement equations, reached R² values of respectively only 0.44, 0.49, and 0.41. Calculation resulted in under- as well as overestimation of REE. Global formulas reached no acceptable correlation in elderly or obese critically ill patients. CONCLUSION: In critically ill adult patients, measured REE poorly correlated with calculated values, regardless what formula was used. Our findings underscore the important role of IC to adequately estimate energy requirements in this particularly frail population.

An unusual case of acute psychosis in an adolescent.

Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is a severe form of encephalitis that has been identified within the context of acute neuropsychiatric manifestations. We report the case of an 18-year-old adolescent referred for a first episode of acute psychosis. The clinical picture rapidly deteriorated to a state of catatonia, decreased consciousness and autonomic instability. Detection of highly positive anti-NMDA-R antibodies confirmed the diagnosis of anti-NMDA-R encephalitis. Immunosuppressive treatment and repeated plasma exchange resulted in slow recovery. The literature on diagnosis and treatment of this specific type of encephalitis is reviewed.

Intermittent subglottic secretion drainage may cause tracheal damage in patients with few oropharyngeal secretions.

OBJECTIVE: Injurious prolapse of tracheal mucosa into the suction port has been reported in up to 50% of intubated patients receiving continuous aspiration of subglottic secretions. We investigated whether similar injury could be inflicted by automated intermittent aspiration. METHODS: Six consecutive patients, intubated with the Mallinckrodt TaperGuard Evac™ endotracheal tube, were studied. A flow sensor was placed between the vacuum regulating system and the mucus collector. Intermittent suctioning was performed at a pressure of -125 mmHg with a 25s interval and duration of 15s. After 24h, a CT scan of the tracheal region was performed. RESULTS: Excessive negative suction pressure, a fast drop in aspiration flow to zero, and important "swinging" movements of secretions in the evacuation line were observed in all patients. Oral instillation of antiseptic mouthwash restored normal aspiration flow and secretion mobility. CT imaging showed marked entrapment of tracheal mucosa into the suction port in all patients. CONCLUSION: In patients with few oropharyngeal secretions, automated intermittent subglottic aspiration may result in significant and potential harmful invagination of tracheal mucosa into the suction lumen. A critical amount of fluid must be present in the oropharynx to assure adequate and safe aspiration.

Phosphate induced crystal acute kidney injury - an under-recognized cause of acute kidney injury potentially leading to chronic kidney disease: case report and review of the literature.

Acute phosphate nephropathy or nephrocalcinosis is a tubulointerstitial nephropathy characterized by tubular calcium phosphate deposition - crystal nephropathy - and slowly progressive renal insufficiency during or following treatment with preparations containing sodium phosphate. We report a patient who developed nephrocalcinosis (crystal induced acute kidney injury) following the administration of a combination of oral and rectal sodium phosphate for treatment of postoperative constipation. A timely renal replacement therapy procedure may reverse the process of crystallization and the irreversible slope towards chronic dialysis.

Boerhaave's Syndrome: Still a Diagnostic and Therapeutic Challenge in the 21st Century.

Boerhaave's syndrome is a rare but potentially fatal condition characterised by a transmural tear of the distal oesophagus induced by a sudden increase in pressure. Diagnosis is challenging as the classic triad of vomiting, abdominal or chest pain, and subcutaneous emphysema is absent in many patients. Management is multidisciplinary and relies on rapid, distinct, and repeated imaging. Treatment has not been standardised and may be conservative, endoscopic, or surgical. We present a typical case which illustrates possible diagnostic pitfalls and the therapeutic conundrum surrounding management of the syndrome. Based on time of presentation and eventual presence of sepsis, a therapeutic algorithm is proposed.

Handling continuous renal replacement therapy-related adverse effects in intensive care unit patients: the dialytrauma concept.

Continuous renal replacement therapy (CRRT) is increasingly used for the management of critically ill patients. As a consequence, the incidence of complications that accompany CRRT is also rising. However, a standardized approach for preventing or minimizing these adverse events is lacking. Dialytrauma is a newly proposed concept that encompasses all harmful adverse events related to CRRT while providing a framework for prevention or, at the least, early recognition of these events in order to attenuate the consequences. A mainstay of this approach is the utilization of a dedicated checklist for improving CRRT quality and patient safety. In this context, we discuss the most important adverse effects of CRRT and review current strategies to minimize them.

Sudden cardiac arrest during pregnancy: a rare complication of acquired maternal diaphragmatic hernia.

Acute cardiac arrest during pregnancy is a rare but devastating event. Major causes are haemorrhagic, septic or anaphylactic shock, trauma, pulmonary or amniotic fluid embolism, and congenital or acquired cardiac disease. We present a case of massive intrathoracic migration of viscera through a left diaphragmatic hernia in a pregnant multipara, causing acute obstructive shock and cardiac arrest. Complications of intrathoracic herniation occur when the intruding viscera cause left lung and cardiac compression or mediastinal "tamponade" with decreased venous return. Intrathoracic strangulation of viscera is also common and may cause ischaemia, gangrene and eventual perforation. Sudden cardiac arrest as first sign of left diaphragmatic rupture during pregnancy, however, has rarely been described. In contrast with our patient, this catastrophic event is mostly seen in nulli- and primipara with a known congenital left diaphragmatic defect. Management of a diaphragmatic hernia depends on the clinical presentation and the period of gestation during which it is detected. Despite prolonged resuscitation with more than 1 hour of chest compressions, our patient recovered completely.

New insights regarding rationale, therapeutic target and dose of hemofiltration and hybrid therapies in septic acute kidney injury.

Mediator removal from tissue (capillary blood compartment, CABC) and transport to the central circulation (central blood compartment, CEBC) must be effective. Effectiveness through a passive mechanism seems unlikely as the surface of CEBC (30 m(2)) is smaller than CABC (300 m(2)) whereby the former will be a limiting factor in passive transport. According to studies, a high exchange volume can induce an 80-fold increase in lymphatic flow. This results in displacement (active transport) of mediators to CEBC. Recent studies have shown that the delivered dose constitutes the mainstay of continuous renal replacement therapy. However, these results are not likely to change the recommendation: 35 ml/kg/h, adjusted for predilution, in septic acute kidney injury (AKI). Recently, studies were focusing on global intensive care unit AKI. In non-septic AKI, those studies show that 20-25 ml/kg/h was optimal. The DO-RE-MI trial underscored the importance of delivery which could be obtained by targeting doses between 5 and 10 ml/kg/h higher than prescribed. Until the IVOIRE trial becomes available, septic AKI should be treated by continuous veno-venous hemofiltration at 35 ml/kg/h. In non-septic AKI, 25 ml/kg/h remains optimal.

Septic acute kidney injury: the culprit is inflammatory apoptosis rather than ischemic necrosis.

For a long time, acute kidney injury (AKI) was considered to be a primarily hemodynamic condition characterized by a reduction of renal blood flow, induced by either cardiogenic or distributive (septic) shock. Consequently, all efforts to treat AKI were essentially concentrated on increasing renal flow by enhancing cardiac flow output and perfusion pressure. At the beginning of this decade, Bellomo and co-workers produced new and intriguing data in an animal model of septic AKI that undermined existing concepts. They observed that medullar and cortical renal blood flow were both maintained and even increased in septic shock, underscoring that septic AKI was a totally different physiological phenomenon than nonseptic AKI. Also, apoptosis was found to play a more important role in sepsis and septic shock than pure necrosis. Despite these findings, the role of apoptosis as a main mechanism of organ dysfunction remains topic of debate.

Adjunctive steroid treatment in acute bacterial meningitis. "To do or not to do: that is the question".

In experimental bacterial meningitis, adjunctive steroid treatment reduces the inflammatory response in the cerebrospinal fluid and subarachnoidal space, thereby improving neurological outcome. The clinical application of this concept was sustained by the European Dexamethasone Study which showed a beneficial effect of dexamethasone on neurological outcome and mortality in adult patients with bacterial--in particular S. pneumoniae-- meningitis. A thorough analysis of the data of this landmark trial as well as results from more recent trials in children and adults with bacterial meningitis worldwide do not support the use of adjunctive dexamethasone in meningitis. Moreover, dexamethasone may have detrimental effects with regard to antibiotic efficacy and late severe neurological complications. Until further data about steroid use in bacterial meningitis becomes available, we propose that dexamethasone therapy in this setting should be abandoned.

90-day follow-up of patients treated with Drotrecogin Alfa (activated) for severe sepsis: a Belgian open label study.

INTRODUCTION: Severe sepsis is the major cause of mortality in intensive care units (ICUs). The BOOST study (= B (Belgian) OO (Open Label) ST (Study)) is a Belgian open-label trial designed to pragmatically assess the safety and efficacy of Drotrecogin Alfa (activated) (DAA), the only registered treatment in this indication with favourable ratio benefit/risk. METHODOLOGY: Adult patients with severe sepsis and 2 or more sepsis-induced organ dysfunctions (OD) within the 48-hour period preceding the treatment (DAA at 24 microg/kg/h for 96 hours), were included between January 2003 and October 2003. Platelet count < 30 000/mm3 and increased risk for bleeding were exclusion criteria. Mortality and location were evaluated at 28 and 90 days. RESULTS: Of the 100 included patients, 97 (median age: 66 years; men/women: 57/40) were treated and completed the study. The predominant infection sites were lung (49%) and abdomen (29%) and 35% had had recent surgery. The mean and median numbers of OD were 3.4 and 3.0, respectively, and most patients (80 %; 77/97) had 3 or more organ failures at baseline, predominantly respiratory (95%) and cardiovascular (87%). The mean APACHE II score was 25.3 (range: 6-53). The 28-day mortality rate was 32.0% (90% CI: 24.2-39.7) and increased with the number of OD: from 15% (1.9-28.1) for2 ODs, to 71% (52.4-88.8) for 5 ODs. At day 28, the 66 surviving patients were located in general ward (35%), in the ICU (32%) or at home (30%). The 90-day mortality rate was 42% (90% CI: 34.0-50.5), with most of the survivors (73%) staying at home. Eight serious adverse events, including 4 bleedings, were reported between study days 2 and 5, in 5 patients (5.2%) and led to death in 2 patients (2.1%). CONCLUSION: Despite a higher severity of illness at baseline, this phase IV open-label long-term study in Belgian ICUs shows consistent results with previous studies with DAA. Importantly, most of the surviving patients at day 90 were staying at home.

Clinical pharmacology of exogenously administered alkaline phosphatase.

PURPOSE: To evaluate the clinical pharmacology of exogenous alkaline phosphatase (AP). METHODS: Randomized, double-blind, placebo-controlled sequential protocols of (1) ascending doses and infusion duration (volunteers) and (2) fixed dose and duration (patients) were conducted at clinical pharmacology and intensive care units. A total of 103 subjects (67 male volunteers and 36 patients with severe sepsis) were administered exogenous, 10-min IV infusions (three ascending doses) or 24-72 h continuous (132.5-200 U kg(-1) 24 h(-1)) IV infusion with/without preceding loading dose and experimental endotoxemia for evaluations of pharmacokinetics, pharmacodynamics, safety parameters, antigenicity, inflammatory markers, and outcomes. RESULTS: Linearity and dose-proportionality were shown during 10-min infusions. The relatively short elimination half-life necessitated a loading dose to achieve stable enzyme levels. Pharmacokinetic parameters in volunteers and patients were similar. Innate immunity response was not significantly influenced by AP, while renal function significantly improved in sepsis patients. CONCLUSIONS: The pharmacokinetics of exogenous AP is linear, dose-proportional, exhibit a short half-life, and are not influenced by renal impairment or dialysis.

Do-not-resuscitate orders in the critically ill patient--an observational study with special emphasis on withholding of renal replacement therapy.

We examined the process, consequences and impact of writing a Do-Not-Resuscitate (DNR) order in a cohort of critically-ill ICU patients. Special emphasis was given to the DNR order including withholding renal replacement therapy. A DNR code was mainly written in the first week following ICU admission and more often given to medical, older and sicker patients. Patients never actively participated in the decision and in only half of the cases the DNR order was discussed with relatives. Mortality of all patients studied was 21% of whom 67% died with a DNR order. In our population, the final in-hospital mortality rate of DNR-coded patients was 100%, because the DNR status was ordered when the patients were already very sick. DNR-coded patients died after a longer mean length of ICU stay than patients without a code. Withholding renal replacement therapy was commonly added to the DNR order even if renal failure either was not present or never developed.

Sepsis-related acute kidney injury: a protective effect of drotrecogin alpha (activated) treatment?

BACKGROUND: Drotrecogin alpha activated (DrotAA) is licensed for treatment of patients with severe sepsis and organ failure. Among the latter, acute kidney injury (AKI), defined as the persistence of oligo-anuria following adequate resuscitation, is one of the most apprehended. We conducted a prospective, observational, and controlled study to test the hypothesis that DrotAA beneficially affected the evolution and outcome of AKI, complicating acute sepsis-induced cardiopulmonary failure. METHODS: Forty-six patients were studied. Thirty subjects received standard treatment for sepsis without DrotAA. In the remaining 16 patients, DrotAA was added as a continuous infusion of 24 microg/kg/h for 96 h. RESULTS: Mean age, causes of sepsis, and severity/organ failure scores were comparable between patients treated with or without DrotAA. Mortality at 28 days was high and comparable between both treatment groups (56% vs. 69%, DrotAA vs. no DrotAA; P=0.5). When oligo-anuria was present at the start of the study, it persisted during treatment in all patients, with no significant difference between groups. Both treatment groups presented with baseline mean daily fractional excretion of sodium values >2% that remained high during the observation period, regardless of whether DrotAA was given or not. Kidney histology showed a preserved renal architecture with tubular necrosis in all specimens. Similar glomerular, tubulo-interstitial, and vascular alterations were present in both treatment groups. CONCLUSION: In this small cohort of patients with severe sepsis who received adjuvant DrotAA treatment, no effect on urine output, tubular function, or mortality could be demonstrated.

A registry of patients treated with drotrecogin alfa (activated) in Belgian intensive care units--an observational study.

BACKGROUND: Drotrecogin alfa (activated) [DrotAA] is the only specific sepsis therapy that has been shown to reduce mortality. The objectives of this study were to document the profile of patients treated with DrotAA in Belgian intensive care units (ICUs), using data from a database established as part of drug reimbursement conditions in Belgium, and to compare the observed hospital mortality of these patients with their expected mortality, calculated using data from non-DrotAA-treated patients from the Belgian section of PROGRESS, a separate, voluntary, international sepsis registry collecting data from patients with severe sepsis. MATERIAL AND METHODS: Data from the non-DrotAA-treated patients in PROGRESS were used to calculate the expected mortality rates for DrotAA-treated patients in the Belgian registry. Using a logistic regression equation, these rates were controlled for age and the presence or absence of organ dysfunction in each of 5 organ systems. The same logistic regression technique was used to control the mortality rates observed in the DrotAA-treated patients from the Belgian registry for age and the presence or absence of each of the 5 organ dysfunctions. Adjusted expected and observed hospital mortality rates could then be compared. RESULTS: There were 436 DrotAA patients in the Belgian registry. Almost all the patients (99.5%) had at least 2 organ failures and the hospital mortality was 51.6%. Two hundred and eighty-six of the patients had enough baseline data to be included in the regression model. Using data from the PROGRESS non-DrotAA patients, the predicted hospital mortality, controlled for age and organ dysfunction, of Belgian registry patients, had they not been treated with DrotAA, was 63.5%. The observed hospital mortality, again controlled for age and organ dysfunction, of the 286 Belgian registry patients was 50.7%, implying an adjusted absolute mortality reduction of 12.8%. CONCLUSIONS: Comparing Belgian reimbursement registry data with those of a voluntary severe sepsis register provides support for the observation that DrotAA reduces mortality rates in severe sepsis and septic shock.