Complications of regional citrate anticoagulation: accumulation or overload?

Regional citrate anticoagulation (RCA) is now recommended over systemic heparin for continuous renal replacement therapy in patients without contraindications. Its use is likely to increase throughout the world. However, in the absence of citrate blood level monitoring, the diagnosis of citrate accumulation, the most feared complication of RCA, remains relatively complex. It is therefore commonly mistaken with other conditions. This review aims at providing clarifications on RCA-associated acid-base disturbances and their management at the bedside. In particular, the authors wish to propose a clear distinction between citrate accumulation and net citrate overload.

Early initiation of peritoneal dialysis in neonates and infants with acute kidney injury following cardiac surgery is associated with a significant decrease in mortality.

Association between early renal replacement therapy and better survival has been reported in adults with postoperative kidney injury, but not in children undergoing cardiac surgery. We conducted a retrospective cohort study of 146 neonates and infants requiring peritoneal dialysis following cardiac surgery in a tertiary referral hospital. A propensity score was used to limit selection bias due to timing of dialysis, and included baseline and intraoperative characteristics, requirement for postoperative extracorporeal membrane oxygenation, and creatinine clearance variation. Inverse probability of treatment weighting resulted in good balance between groups for all baseline and intraoperative variables. After weighting, 30-day and 90-day mortality were compared between the 109 patients placed on dialysis early, within the first day of surgery, and those with delayed dialysis, commencing on the second day of surgery or later, using logistic regression and survival analysis. Mortality was 28.1% at 30 days, and was 36.3% during follow-up. Early dialysis was associated with a 46.7% decrease in the 30-day and a 43.5% decrease in the 90-day mortality rate when compared with delayed dialysis. All other short-term outcome variables were similar. Thus, initiation of peritoneal dialysis on the day of or the first day following surgery was associated with a significant decrease in mortality in neonates and infants with acute kidney injury.

Challenging the Ex Vivo Lung Perfusion Procedure With Continuous Dialysis in a Pig Model.

BACKGROUND: Normothermic ex vivo lung perfusion (EVLP) increases the pool of donor lungs by requalifying marginal lungs refused for transplantation through the recovery of macroscopic and functional properties. However, the cell response and metabolism occurring during EVLP generate a nonphysiological accumulation of electrolytes, metabolites, cytokines, and other cellular byproducts which may have deleterious effects both at the organ and cell levels, with impact on transplantation outcomes. METHODS: We analyzed the physiological, metabolic, and genome-wide response of lungs undergoing a 6-h EVLP procedure in a pig model in 4 experimental conditions: without perfusate modification, with partial replacement of fluid, and with adult or pediatric dialysis filters. RESULTS: Adult and pediatric dialysis stabilized the electrolytic and metabolic profiles while maintaining acid-base and gas exchanges. Pediatric dialysis increased the level of IL-10 and IL-6 in the perfusate. Despite leading to modification of the perfusate composition, the 4 EVLP conditions did not affect the gene expression profiles, which were associated in all cases with increased cell survival, cell proliferation, inflammatory response and cell movement, and with inhibition of bleeding. CONCLUSIONS: Management of EVLP perfusate by periodic replacement and continuous dialysis has no significant effect on the lung function nor on the gene expression profiles ex vivo. These results suggest that the accumulation of dialyzable cell products does not significantly alter the lung cell response during EVLP, a finding that may have impact on EVLP management in the clinic.

Clustering ICU patients with sepsis based on the patterns of their circulating biomarkers: A secondary analysis of the CAPTAIN prospective multicenter cohort study.

BACKGROUND: Although sepsis is a life-threatening condition, its heterogeneous presentation likely explains the negative results of most trials on adjunctive therapy. This study in patients with sepsis aimed to identify subgroups with similar immune profiles and their clinical and outcome correlates. METHODS: A secondary analysis used data of a prospective multicenter cohort that included patients with early assessment of sepsis. They were described using Predisposition, Insult, Response, Organ failure sepsis (PIRO) staging system. Thirty-eight circulating biomarkers (27 proteins, 11 mRNAs) were assessed at sepsis diagnosis, and their patterns were determined through principal component analysis (PCA). Hierarchical clustering was used to group the patients and k-means algorithm was applied to assess the internal validity of the clusters. RESULTS: Two hundred and three patients were assessed, of median age 64.5 [52.0-77.0] years and SAPS2 score 55 [49-61] points. Five main patterns of biomarkers and six clusters of patients (including 42%, 21%, 17%, 9%, 5% and 5% of the patients) were evidenced. Clusters were distinguished according to the certainty of the causal infection, inflammation, use of organ support, pro- and anti-inflammatory activity, and adaptive profile markers. CONCLUSIONS: In this cohort of patients with suspected sepsis, we individualized clusters which may be described with criteria used to stage sepsis. As these clusters are based on the patterns of circulating biomarkers, whether they might help to predict treatment responsiveness should be addressed in further studies. TRIAL REGISTRATION: The CAPTAIN study was registered on clinicaltrials.gov on June 22, 2011, # NCT01378169.

Misleading abdominal pain following extracorporeal renal lithotripsy.

INTRODUCTION: Extracorporeal shockwave lithotripsy (ESWL) is a useful technique for the treatment of kidney and urinary tract stones but appears also to cause some extrarenal complications. CASE PRESENTATION: We report the case of a 33-year-old Caucasian man with a history of Crohn's disease who presented septic shock due to a jejunum perforation 6 h following an ESWL for a right ureteral stone. The perforation, which occurred at the exact site of a previous surgical anastomosis, was revealed on a CT scan which found an unusual aspect probably due to cavitation and bubbles formation induced by ESWL. CONCLUSION: This case emphasizes the particular aspect of CT scan and the extrarenal potential danger of the ESWL procedure. Some precautions and dedicated patient information must be taken when used in patients with chronic inflammation of the digestive tract or history of intestinal surgery.

Early tracheotomy versus prolonged endotracheal intubation in unselected severely ill ICU patients.

OBJECTIVE: Although several advantages are attributed to tracheotomy in ICU patients requiring mechanical ventilation (MV), true benefits and the optimal timing of tracheotomy remain controversial. In this study, we compared early tracheotomy (ET) with prolonged intubation (PI) in severely ill patients requiring prolonged MV. DESIGN: Prospective, randomized study. SETTING: Twenty-five medical and surgical ICUs in France. PATIENTS: Patients expected to require MV > 7 days. MEASUREMENTS AND RESULTS: Patients were randomised to either (open or percutaneous) ET within 4 days or PI. The primary end-point was 28-day mortality. Secondary end-points were: the incidence of ICU-acquired pneumonia, number of d1-d28 ventilator-free days, time spent in the ICU, 60-day mortality, number of septic episodes, amount of sedation, comfort and laryngeal and tracheal complications. A sample size of 470 patients was considered necessary to obtain a reduction from 45 to 32% in 28-day mortality. After 30 months, 123 patients had been included (ET = 61, PI = 62) in 25 centres and the study was prematurely closed. All group characteristics were similar upon admission to ICU. No difference was found between the two groups for any of the primary or secondary end-points. Greater comfort was the sole benefit afforded by tracheotomy after subjective self-assessment by patients. CONCLUSIONS: The trial did not demonstrate any major benefit of tracheotomy in a general population of ICU patients, as suggested in a previous meta-analysis, but was underpowered to draw any firm conclusions. The potential advantage of ET may be restricted to selected groups of patients.

Circulating biomarkers may be unable to detect infection at the early phase of sepsis in ICU patients: the CAPTAIN prospective multicenter cohort study.

PURPOSE: Sepsis and non-septic systemic inflammatory response syndrome (SIRS) are the same syndromes, differing by their cause, sepsis being secondary to microbial infection. Microbiological tests are not enough to detect infection early. While more than 50 biomarkers have been proposed to detect infection, none have been repeatedly validated. AIM: To assess the accuracy of circulating biomarkers to discriminate between sepsis and non-septic SIRS. METHODS: The CAPTAIN study was a prospective observational multicenter cohort of 279 ICU patients with hypo- or hyperthermia and criteria of SIRS, included at the time the attending physician considered antimicrobial therapy. Investigators collected blood at inclusion to measure 29 plasma compounds and ten whole blood RNAs, and-for those patients included within working hours-14 leukocyte surface markers. Patients were classified as having sepsis or non-septic SIRS blindly to the biomarkers results. We used the LASSO method as the technique of multivariate analysis, because of the large number of biomarkers. RESULTS: During the study period, 363 patients with SIRS were screened, 84 having exclusion criteria. Ninety-one patients were classified as having non-septic SIRS and 188 as having sepsis. Eight biomarkers had an area under the receiver operating curve (ROC-AUC) over 0.6 with a 95% confidence interval over 0.5. LASSO regression identified CRP and HLA-DRA mRNA as being repeatedly associated with sepsis, and no model performed better than CRP alone (ROC-AUC 0.76 [0.68-0.84]). CONCLUSIONS: The circulating biomarkers tested were found to discriminate poorly between sepsis and non-septic SIRS, and no combination performed better than CRP alone.

Haemodialysis catheters in the intensive care unit.

Ten to 15% of critically ill patients need renal replacement therapy (RRT) for severe acute kidney injury. The dialysis catheter is critical for RRT quality and efficiency. Catheters have several properties that must be optimized to promote RRT success. The distal tip has to be located in a high blood flow location, which means central venous territory. Therefore, catheters are mostly inserted into the right internal jugular vein or in femoral veins. External diameter should vary from 12 to 16 Fr in order to ensure adequate blood flow inside the catheter. Lumen shapes are theoretically designed to limit thrombotic risk with low turbulences and frictional forces against the internal wall. With low aspiration pressure, distal tip shape has to deliver sufficient blood flow, while limiting recirculation rate. Catheter material should be biocompatible. Despite in vitro data, no strong evidence supports the use of coated catheters in the ICU in order to reduce infectious risk. Antibiotic "lock" solutions are not routinely recommended. Ultrasound guidance for catheterization significantly decreases mechanical complications. Clinicians should select the optimal catheter according to patient body habitus, catheter intrinsic properties and RRT modality to be used.

Effects of laparoscopic pneumoperitoneum and changes in position on arterial pulse pressure wave-form: comparison between morbidly obese and normal-weight patients.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is commonly indicated in morbidly obese patients. There is controversy regarding the hemodynamic effects of pneumoperitoneum (PNP) in obese patients. PNP and changes in body posture have complex effects on venous return that may be detected by respiratory changes in the arterial pressure waveform. The aim of this study was to compare pneumoperitoneum-induced and reverse Trendelenburg (RT) changes in arterial pulse pressure in obese and normal-weight patients. METHODS: 15 morbidly obese patients undergoing LAGB were compared to 15 normal-weight patients undergoing laparoscopic surgery. Arterial pressure was non-invasively recorded using an arterial tonometer. Respiratory changes in pulse pressure (deltaPp) were recorded in the supine position without and with PNP, and in RT position with pneumoperitoneum. RESULTS: PNP increased deltaPp values in normal weight (P<0.001), but not in obese patients. RT position increased deltaPp values in obese patients, but did not cause additional changes in normal-weight patients. CONCLUSIONS: Unlike normal-weight patients, PNP in the supine position has minimal effect on the arterial pulse-pressure wave-form in obese patients. This observation may reflect physiological differences in total blood volume and loading conditions of the heart between morbidly obese and normal-weight patients, which affect venous return during PNP. Differences in abdominal vascular zone conditions between obese and normal weight-patients may explain these results.

Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies).

Acute kidney injury (AKI) is a syndrome that has progressed a great deal over the last 20 years. The decrease in urine output and the increase in classical renal biomarkers, such as blood urea nitrogen and serum creatinine, have largely been used as surrogate markers for decreased glomerular filtration rate (GFR), which defines AKI. However, using such markers of GFR as criteria for diagnosing AKI has several limits including the difficult diagnosis of non-organic AKI, also called "functional renal insufficiency" or "pre-renal insufficiency". This situation is characterized by an oliguria and an increase in creatininemia as a consequence of a reduction in renal blood flow related to systemic haemodynamic abnormalities. In this situation, "renal insufficiency" seems rather inappropriate as kidney function is not impaired. On the contrary, the kidney delivers an appropriate response aiming to recover optimal systemic physiological haemodynamic conditions. Considering the kidney as insufficient is erroneous because this suggests that it does not work correctly, whereas the opposite is occurring, because the kidney is healthy even in a threatening situation. With current definitions of AKI, normalization of volaemia is needed before defining AKI in order to avoid this pitfall.

Effects of inhaled nitric oxide administration on early postoperative mortality in patients operated for correction of atrioventricular canal defects.

OBJECTIVE: Postoperative pulmonary hypertension (POPH) substantially increases mortality after repair of congenital heart diseases. Inhaled nitric oxide (NO) has been reported as an effective and specific means of controlling POPH crisis. No randomized, placebo-controlled study has addressed the ability of NO administration to reduce mortality. Such a trial could raise ethical questions. DESIGN: Observational study with historical control subjects based on multivariate confounder scores. SETTING: Surgical pediatric ICU in a university hospital. PATIENTS: Two hundred ninety-four records of patients operated on for atrioventricular (AV) canal between 1984 and 1994 who presented with severe POPH. INTERVENTIONS: All variables found to be predictive for death by univariate tests were entered in a multivariate forward stepwise logistic regression model. Two paired groups regarding risk factors for death and only differing for POPH treatment (NO or conventional treatment) were constructed on the basis of predicted values obtained from this model. Twenty-five patients received NO, and 39 control patients, operated on between 1984 and 1994, received conventional treatment for POPH. MEASUREMENTS AND RESULTS: Postoperative pulmonary pressure, date of operation, and occurrence of an infectious complication were retained in the model. The comparison between the two paired groups showed a significant difference in mortality (24%; 95% confidence interval [CI], 7 to 41%; vs 56%; 95% CI, 37 to 75%, respectively; p = 0.02). CONCLUSIONS: This study suggests that there is a high probability for postoperative mortality reduction associated with administration of inhaled NO when severe POPH occurs in children operated for complete repair of AV canal.

Study protocol: the DOse REsponse Multicentre International collaborative initiative (DO-RE-MI).

INTRODUCTION: Current practices for renal replacement therapy in intensive care units (ICUs) remain poorly defined. The DOse REsponse Multicentre International collaborative initiative (DO-RE-MI) will address the issue of how the different modes of renal replacement therapy are currently chosen and performed. Here, we describe the study protocol, which was approved by the Scientific and Steering Committees. METHODS: DO-RE-MI is an observational, multicentre study conducted in ICUs. The primary end-point will be the delivered dose of dialysis, which will be compared with ICU mortality, 28-day mortality, hospital mortality, ICU length of stay and number of days of mechanical ventilation. The secondary end-point will be the haemodynamic response to renal replacement therapy, expressed as percentage reduction in noradrenaline (norepinephrine) requirement. Based on the the sample analysis calculation, at least 162 patients must be recruited. Anonymized patient data will be entered online in electronic case report forms and uploaded to an internet website. Each participating centre will have 2 months to become acquainted with the electronic case report forms. After this period official recruitment will begin. Patient data belong to the respective centre, which may use the database for its own needs. However, all centres have agreed to participate in a joint effort to achieve the sample size needed for statistical analysis. CONCLUSION: The study will hopefully help to collect useful information on the current practice of renal replacement therapy in ICUs. It will also provide a centre-based collection of data that will be useful for monitoring all aspects of extracorporeal support, such as incidence, frequency, and duration.

[Perioperative acute kidney injury and failure]. / Insuffisance et agression rénales aiguës périopératoires.

Perioperative period is very likely to lead to acute renal failure because of anesthesia (general or perimedullary) and/or surgery which can cause acute kidney injury. Characterization of acute renal failure is based on serum creatinine level which is imprecise during and following surgery. Studies are based on various definitions of acute renal failure with different thresholds which skewed their comparisons. The RIFLE classification (risk, injury, failure, loss, end stage kidney disease) allows clinicians to distinguish in a similar manner between different stages of acute kidney injury rather than using a unique definition of acute renal failure. Acute renal failure during the perioperative period can mainly be explained by iatrogenic, hemodynamic or surgical causes and can result in an increased morbi-mortality. Prevention of this complication requires hemodynamic optimization (venous return, cardiac output, vascular resistance), discontinuation of nephrotoxic drugs but also knowledge of the different steps of the surgery to avoid further degradation of renal perfusion. Diuretics do not prevent acute renal failure and may even push it forward especially during the perioperative period when venous retourn is already reduced. Edema or weight gain following surgery are not correlated with the vascular compartment volume, much less with renal perfusion. Treatment of perioperative acute renal failure is similar to other acute renal failure. Renal replacement therapy must be mastered to prevent any additional risk of hemodynamic instability or hydro-electrolytic imbalance.

Predictive performance of urine neutrophil gelatinase-associated lipocalin for dialysis requirement and death following cardiac surgery in neonates and infants.

BACKGROUND AND OBJECTIVES: Urine neutrophil gelatinase-associated lipocalin (uNGAL) has been shown to accurately predict and allow early detection of AKI, as assessed by an increase in serum creatinine in children and adults. The present study explores the accuracy of uNGAL for the prediction of severe AKI-related outcomes in neonates and infants undergoing cardiac surgery: dialysis requirement and/or death within 30 days. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Prospective, observational cohort study conducted in a tertiary referral pediatric cardiac intensive care unit, including 75 neonates and 125 infants undergoing surgery with cardiopulmonary bypass between August 1, 2010, and May 31, 2011. Urine samples were collected before surgery and at median of five time points within 48 hours of bypass. Urine NGAL was quantified as absolute concentration, creatinine-normalized concentration, and absolute excretion rate, and a clusterization algorithm was applied to the individual uNGAL kinetics. The accuracy for the prediction of the outcome was assessed using receiver-operating characteristic areas, likelihood ratios, diagnostic odds ratios, net reclassification index, integrated reclassification improvement, and number needed to screen. RESULTS: A total of 1176 urine samples were collected. Of all patients, 8% required dialysis and 4% died. Three clusters of uNGAL kinetics were identified, including patients with significantly different outcomes. The uNGAL level peaked between 1 and 3 hours of bypass and remained high in half of all patients who required dialysis or died. The uNGAL levels measured within 24 hours of bypass accurately predicted the outcome and performed best after normalization to creatinine, with varying cutoffs according to the time elapsed since bypass. The number needed to screen to correctly identify the risk of dialysis or death in one patient varied between 1.5 and 2.6 within 12 hours of bypass. CONCLUSIONS: uNGAL is a valuable predictive tool of dialysis requirement and death in neonates and infants with AKI after cardiac surgery.