Carlos Scheinkestel

Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients

BACKGROUND The optimal intensity of continuous renal-replacement therapy remains unclear. We conducted a multicenter, randomized trial to compare the effect of this therapy, delivered at two different levels of intensity, on 90-day mortality among critically ill patients with acute kidney injury. METHODS We randomly assigned critically ill adults with acute kidney injury to continuous renal-replacement therapy in the form of postdilution continuous venovenous hemodiafiltration with an effluent flow of either 40 ml per kilogram of body weight per hour (higher intensity) or 25 ml per kilogram per hour (lower intensity). The primary outcome measure was death within 90 days after randomization. RESULTS Of the 1508 enrolled patients, 747 were randomly assigned to higher-intensity therapy, and 761 to lower-intensity therapy with continuous venovenous hemodiafiltration. Data on primary outcomes were available for 1464 patients (97.1%): 721 in the higher-intensity group and 743 in the lower-intensity group. The two study groups had similar baseline characteristics and received the study treatment for an average of 6.3 and 5.9 days, respectively (P=0.35). At 90 days after randomization, 322 deaths had occurred in the higher-intensity group and 332 deaths in the lower-intensity group, for a mortality of 44.7% in each group (odds ratio, 1.00; 95% confidence interval [CI], 0.81 to 1.23; P=0.99). At 90 days, 6.8% of survivors in the higher-intensity group (27 of 399), as compared with 4.4% of survivors in the lower-intensity group (18 of 411), were still receiving renal-replacement therapy (odds ratio, 1.59; 95% CI, 0.86 to 2.92; P=0.14). Hypophosphatemia was more common in the higher-intensity group than in the lower-intensity group (65% vs. 54%, P<0.001). CONCLUSIONS In critically ill patients with acute kidney injury, treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days. (ClinicalTrials.gov number, NCT00221013.)

The Laparoscopic Adjustable Gastric Band (Lap-Band®): A Prospective Study of Medium-Term Effects on Weight, Health and Quality of Life

Background: Obesity is now one of our major public health problems. Effective and acceptable treatment options are needed.The Lap-Band® system is placed laparoscopically and allows adjustment of the level of gastric restriction. Methods: A prospective study of 709 severely obese patients was conducted over a 6-year period at a university-based multidisciplinary referral center. After extensive preoperative evaluation, patients with a body mass index >35 were treated by LapBand® placement. Close follow-up with progressive adjustment of gastric restriction continued permanently. Medical co-morbidities were monitored as part of comprehensive prospective data collection. Results: There have been no deaths perioperatively or during follow-up. Significant perioperative adverse events occurred in 1.2% only. Reoperation has been needed for prolapse (slippage) in 12.5%, erosion of the band into the stomach in 2.8% and for tubing breaks in 3.6%. A steady progression of weight loss has occurred through the duration of the study with 52 ± 19 %EWL at 24 months (n=333), 53±22 %EWL at 36 months (n=264), 52 ± 24 %EWL at 48 months (n=108), 54 ± 24 %EWL at 60 months (n=30), and 57 ± 15% EWL at 72 months (n=10). Major improvements have occurred in diabetes, asthma, gastroesophageal reflux, dyslipidemia, sleep apnea and depression. Quality of life as measured by Rand SF-36 shows highly significant improvement. Conclusions: Placement of the Lap-Band® system provides safe and effective control of severe obesity. The effect on weight loss is durable and is associated with major improvement in health and quality of life. It has the potential to provide a broadly acceptable option for this common and serious disease.

Predicting Survival after Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Failure. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score

RATIONALE Increasing use of extracorporeal membrane oxygenation (ECMO) for acute respiratory failure may increase resource requirements and hospital costs. Better prediction of survival in these patients may improve resource use, allow risk-adjusted comparison of center-specific outcomes, and help clinicians to target patients most likely to benefit from ECMO. OBJECTIVES To create a model for predicting hospital survival at initiation of ECMO for respiratory failure. METHODS Adult patients with severe acute respiratory failure treated by ECMO from 2000 to 2012 were extracted from the Extracorporeal Life Support Organization (ELSO) international registry. Multivariable logistic regression was used to create the Respiratory ECMO Survival Prediction (RESP) score using bootstrapping methodology with internal and external validation. MEASUREMENTS AND MAIN RESULTS Of the 2,355 patients included in the study, 1,338 patients (57%) were discharged alive from hospital. The RESP score was developed using pre-ECMO variables independently associated with hospital survival on logistic regression, which included age, immunocompromised status, duration of mechanical ventilation before ECMO, diagnosis, central nervous system dysfunction, acute associated nonpulmonary infection, neuromuscular blockade agents or nitric oxide use, bicarbonate infusion, cardiac arrest, PaCO2, and peak inspiratory pressure. The receiver operating characteristics curve analysis of the RESP score was c = 0.74 (95% confidence interval, 0.72-0.76). External validation, performed on 140 patients, exhibited excellent discrimination (c = 0.92; 95% confidence interval, 0.89-0.97). CONCLUSIONS The RESP score is a relevant and validated tool to predict survival for patients receiving ECMO for respiratory failure.

Prospective randomized trial to assess caloric and protein needs of critically ill, anuric, ventilated patients requiring continuous renal replacement therapy

OBJECTIVES We measured the energy and protein needs in 50 sequential, critically ill, ventilated patients requiring continuous renal replacement therapy (CRRT) for renal failure by using indirect calorimetry and three sequential isocaloric protein-feeding regimes of 1.5, 2.0, and 2.5 g. kg(-1). d(-1). We also assessed the compliance of actual feeding with target feeding and correlated the predictive energy requirements of the formulae with the actual energy expenditure (EE) measured by indirect calorimetry. We also determined whether these feeding regimes affected patient outcome. METHODS The energy and protein needs of 50 consecutive, critically ill patients (31 male; age 53.3 +/- 17.4 y; Acute Physiology and Chronic Health Evaluation (APACHE II) score: 26.0 +/- 8.0; Acute Physiology and Chronic Health Evaluation score predicted risk of death: 50.0 +/- 25.0%) were assessed by using indirect calorimetry and ultrafiltrate nitrogen loss. Entry into this study was on commencement of CRRT. To eliminate any beneficial effect from the passage of time on nitrogen balance, 10 of the 50 patients were randomized to receive 2.0 g. kg(-1). d(-1) throughout the study, and the others received an escalating isocaloric feeding regime (1.5, 2.0, and 2.5 g. kg(-1). d(-1)) at 48-h intervals. Enteral feeding was preferred, but if this was not tolerated or unable to meet target, it was supplemented or replaced by a continuous infusion of total parenteral nutrition. Energy was given to meet caloric requirements as predicted by the Schofield equation corrected by stress factors or based on the metabolic cart readings of EE and was kept constant for all patients throughout the trial. Patients were stabilized on each feeding regime for at least 24 h before samples of dialysate were taken for nitrogen analysis at 8-h intervals on the second day. CRRT was performed by using a blood pump with a blood flow of 100 to 175 mL/min. Dialysate was pumped in and out counter-currently to the blood flow at 2 L/h. A biocompatible polyacrylonitrile hemofilter was used in all cases. RESULTS EE was 2153 +/- 380 cal/d and increased by 56 +/- 24 cal/d (P < 0.0001) throughout the 6-d study period to 2431 +/- 498 cal/d. At study entry, the mean predicted (Schofield) caloric requirement was 2101 +/- 410. Patients received 99% of the predicted energy requirements. However, the mean EE was 11% higher at 2336 +/- 482 calories. This difference was not uniform. If the predicted caloric requirement was less than 2500, the EE exceeded the predicted by an average of 19%. If the predicted caloric requirement was greater than 2500, the EE on average was 6% less than predicted. This relation was significant (P = 0.025) and has not been described previously. Nitrogen balance was inversely related to EE (P = 0.05), positively related to protein intake (P = 0.0075), and more likely to be attained with protein intakes larger than 2 g. kg(-1). d(-1) (P = 0.0001). Nitrogen balance became positive in trial patients over time but were negative in control patients over time (P = 0.0001). Nitrogen balance was directly associated with hospital outcome (P = 0.03) and intensive care unit outcome (P = 0.02). For every 1-g/d increase in nitrogen balance, the probability of survival increased by 21% (P = 0.03; odds ratio, 1.211; 95% confidence limits, 1.017,1.443). Further, although enterally and parenterally fed patients had lower mortalities than predicted, the presence of enteral feeding, even after adjusting for predicted risk of death, had a statistically significant benefit to patient outcome (P = 0.04). CONCLUSIONS This study found that a metabolic cart can improve the accuracy of energy provision and that a protein intake of 2.5 g. kg(-1). d(-1) in these patients increases the likelihood of achieving a positive nitrogen balance and improving survival. Enteral feeding is preferable, but if this is not possible or does not achieve the target, then it should be supplemented by parenteral feeding.

Predicting survival after ECMO for refractory cardiogenic shock: the survival after veno-arterial-ECMO (SAVE)-score

RATIONALE Extracorporeal membrane oxygenation (ECMO) may provide mechanical pulmonary and circulatory support for patients with cardiogenic shock refractory to conventional medical therapy. Prediction of survival in these patients may assist in management of these patients and comparison of results from different centers. AIMS To identify pre-ECMO factors which predict survival from refractory cardiogenic shock requiring ECMO and create the survival after veno-arterial-ECMO (SAVE)-score. METHODS AND RESULTS Patients with refractory cardiogenic shock treated with veno-arterial ECMO between January 2003 and December 2013 were extracted from the international Extracorporeal Life Support Organization registry. Multivariable logistic regression was performed using bootstrapping methodology with internal and external validation to identify factors independently associated with in-hospital survival. Of 3846 patients with cardiogenic shock treated with ECMO, 1601 (42%) patients were alive at hospital discharge. Chronic renal failure, longer duration of ventilation prior to ECMO initiation, pre-ECMO organ failures, pre-ECMO cardiac arrest, congenital heart disease, lower pulse pressure, and lower serum bicarbonate (HCO3) were risk factors associated with mortality. Younger age, lower weight, acute myocarditis, heart transplant, refractory ventricular tachycardia or fibrillation, higher diastolic blood pressure, and lower peak inspiratory pressure were protective. The SAVE-score (area under the receiver operating characteristics [ROC] curve [AUROC] 0.68 [95%CI 0.64-0.71]) was created. External validation of the SAVE-score in an Australian population of 161 patients showed excellent discrimination with AUROC = 0.90 (95%CI 0.85-0.95). CONCLUSIONS The SAVE-score may be a tool to predict survival for patients receiving ECMO for refractory cardiogenic shock (www.save-score.com).

An observational study fluid balance and patient outcomes in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy trial

Objective:To examine associations between mean daily fluid balance during intensive care unit study enrollment and clinical outcomes in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level (RENAL) replacement therapy study. Design:Statistical analysis of data from multicenter, randomized, controlled trials. Setting:Thirty-five intensive care units in Australia and New Zealand. Patients:Cohort of 1453 patients enrolled in the RENAL study. Interventions:We analyzed the association between daily fluid balance on clinical outcomes using multivariable logistic regression, Cox proportional hazards, time-dependent analysis, and repeated measure analysis models. Measurements and Main Results:During intensive care unit stay, mean daily fluid balance among survivors was –234 mL/day compared with +560 mL/day among nonsurvivors (p < .0001). Mean cumulative fluid balance over the same period was –1941 vs. +1755 mL (p = .0003). A negative mean daily fluid balance during study treatment was independently associated with a decreased risk of death at 90 days (odds ratio 0.318; 95% confidence interval 0.24–0.43; p < .000.1) and with increased survival time (p < .0001). In addition, a negative mean daily fluid balance was associated with significantly increased renal replacement-free days (p = .0017), intensive care unit-free days (p < .0001), and hospital-free days (p = .01). These findings were unaltered after the application of different statistical models. Conclusions:In the RENAL study, a negative mean daily fluid balance was consistently associated with improved clinical outcomes. Fluid balance may be a target for specific manipulation in future interventional trials of critically ill patients receiving renal replacement therapy.

Percutaneous tracheostomy in critically ill patients: a prospective, randomized comparison of two techniques.

ObjectiveTo prospectively compare two commonly used methods for percutaneous dilational tracheostomy (PDT) in critically ill patients. DesignProspective, randomized, clinical trial. SettingTrauma and general intensive care units of a university tertiary teaching hospital, which is also a level 1 trauma center. PatientsOne hundred critically ill patients with an indication for PDT. InterventionsPDT with the Ciaglia technique using the Ciaglia PDT introducer set and the Griggs technique using a Griggs PDT kit and guidewire dilating forceps. Measurements and Main ResultsSurgical time, difficulties, and surgical and anesthesia complications were measured at 0–2 hrs, 24 hrs, and 7 days postprocedure. Groups were well matched, and there were no differences between the two methods in surgical time or in anesthesia complications. Major bleeding complications were 4.4 times more frequent with the Griggs PDT kit. With the Ciaglia PDT kit, both intraoperative and at 2 and 24 hrs, surgical complications were less common (p = .023) and the procedure was more often completed without expert assistance (p = .013). Tracheostomy bleeding was not associated with either anticoagulant therapy or an abnormal clotting profile. Multivariate analysis identified the predictors of PDT complications as the Griggs PDT kit (p = .027) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score (p = .041). The significant predictors of time required to complete PDT were the APACHE II score (p = .041), a less experienced operator (p = .0001), and a female patient (p = .013). ConclusionsPatients experiencing PDT with the Ciaglia PDT kit had a lower surgical complication rate (2% vs. 25%), less operative and postoperative bleeding, and less overall technical difficulties than did patients undergoing PDT with the Griggs PDT kit. Ciaglia PDT is, therefore, the preferred technique for percutaneous tracheostomy in critically ill patients.

Impact of Increasing Parenteral Protein Loads on Amino Acid Levels and Balance in Critically Ill Anuric Patients on Continuous Renal Replacement Therapy

OBJECTIVES We wanted to establish optimum protein and glucose intakes during total parenteral nutrition by using a constant caloric but changing protein intake in critically ill, ventilated, anuric patients on continuous renal replacement therapy and measuring amino acid and glucose losses across the hemofilter. METHODS Eleven consecutive, critically ill patients (eight male, age, 43.5 +/- 21.8 y; Acute Physiology and Chronic Health Evaluation II score, 20.5 +/- 7.0; Acute Physiology and Chronic Health Evaluation risk of death: 36.5% +/- 23.0 and 6 +/- 1 impaired organ systems) entered this study. Patients were fed by continuous infusion of a total parenteral mixture consisting of Synthamin (a mixture of essential and non-essential amino acids), 50% dextrose, and intralipid (long-chain triglycerides) to meet caloric requirements as predicted by Schofields equation corrected by stress factors. The amount of protein infused was varied (1 to 2.5 g. kg(-1). d(-1)) by increments of 0.25 g. kg(-1). d(-1). Patients were stabilized on each feeding regimen for at least 24 h before paired samples of blood and dialysate were taken for amino acid and glucose measurements. Continuous renal replacement therapy was performed by using a blood pump with a blood flow of 100 to 175 mL/min. Dialysate was pumped in and out counter-currently to the blood flow at 2 L/h. A biocompatible polyacrylonitrile hemofilter was used in all cases. RESULTS With protein intakes below 2.5 g. kg(-1). d(-1), blood levels of 14% to 57% of the measured amino acids were below the lower limits of the normal range. At 2.5 g. kg(-1). d(-1), all measured amino acids were within the normal range. Amino acid balance became more positive as protein input increased (P = 0.0001). Glucose and amino acid losses were dependent on blood concentration. Overall, 17% (range, 13% to 24%) of infused amino acids and 4% of infused glucose were lost in the dialysate. CONCLUSIONS This study of critically ill, ventilated, anuric patients on continuous renal replacement therapy suggested that increases in protein and glucose are required to account for the increased losses across the hemofilter. A protein intake of 2.5 g. kg(-1). d(-1) appeared to optimize nitrogen balance and correct amino acid deficiencies.

Mechanical ventilation during extracorporeal membrane oxygenation

The timing of extracorporeal membrane oxygenation (ECMO) initiation and its outcome in the management of respiratory and cardiac failure have received considerable attention, but very little attention has been given to mechanical ventilation during ECMO. Mechanical ventilation settings in non-ECMO studies have been shown to have an effect on survival and may also have contributed to a treatment effect in ECMO trials. Protective lung ventilation strategies established for non-ECMO-supported respiratory failure patients may not be optimal for more severe forms of respiratory failure requiring ECMO support. The influence of positive end-expiratory pressure on the reduction of the left ventricular compliance may be a matter of concern for patients receiving ECMO support for cardiac failure. The objectives of this review were to describe potential mechanisms for lung injury during ECMO for respiratory or cardiac failure, to assess the possible benefits from the use of ultra-protective lung ventilation strategies and to review published guidelines and expert opinions available on mechanical ventilation-specific management of patients requiring ECMO, including mode and ventilator settings. Articles were identified through a detailed search of PubMed, Ovid, Cochrane databases and Google Scholar. Additional references were retrieved from the selected studies. Growing evidence suggests that mechanical ventilation settings are important in ECMO patients to minimize further lung damage and improve outcomes. An ultra-protective ventilation strategy may be optimal for mechanical ventilation during ECMO for respiratory failure. The effects of airway pressure on right and left ventricular afterload should be considered during venoarterial ECMO support of cardiac failure. Future studies are needed to better understand the potential impact of invasive mechanical ventilation modes and settings on outcomes.

Mechanical Ventilation Management During Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: A Retrospective International Multicenter Study*

Objective:To describe mechanical ventilation settings in adult patients treated for an acute respiratory distress syndrome with extracorporeal membrane oxygenation and assess the potential impact of mechanical ventilation settings on ICU mortality. Design:Retrospective observational study. Setting:Three international high-volume extracorporeal membrane oxygenation centers. Patients:A total of 168 patients treated with extracorporeal membrane oxygenation for severe acute respiratory distress syndrome from January 2007 to January 2013. Interventions:We analyzed the association between mechanical ventilation settings (i.e. plateau pressure, tidal volume, and positive end-expiratory pressure) on ICU mortality using multivariable logistic regression model and Cox-proportional hazards model. Measurement and Main Results:We obtained detailed demographic, clinical, daily mechanical ventilation settings and ICU outcome data. One hundred sixty-eight patients (41 ± 14 years old; PaO2/FIO2 67 ± 19 mm Hg) fulfilled our inclusion criteria. Median duration of extracorporeal membrane oxygenation and ICU stay were 10 days (6–18 d) and 28 days (16–42 d), respectively. Lower positive end-expiratory pressure levels and significantly lower plateau pressures during extracorporeal membrane oxygenation were used in the French center than in both Australian centers (23.9 ± 1.4 vs 27.6 ± 3.7 and 27.8 ± 3.6; p < 0.0001). Overall ICU mortality was 29%. Lower positive end-expiratory pressure levels (until day 7) and lower delivered tidal volume after 3 days on extracorporeal membrane oxygenation were associated with significantly higher mortality (p < 0.05). In multivariate analysis, higher positive end-expiratory pressure levels during the first 3 days of extracorporeal membrane oxygenation support were associated with lower mortality (odds ratio, 0.75; 95% CI, 0.64–0.88; p = 0.0006). Other independent predictors of ICU mortality included time between ICU admission and extracorporeal membrane oxygenation initiation, plateau pressure greater than 30 cm H2O before extracorporeal membrane oxygenation initiation, and lactate level on day 3 of extracorporeal membrane oxygenation support. Conclusions:Protective mechanical ventilation strategies were routinely used in high-volume extracorporeal membrane oxygenation centers. However, higher positive end-expiratory pressure levels during the first 3 days on extracorporeal membrane oxygenation support were independently associated with improved survival. Further prospective trials on the optimal mechanical ventilation strategy during extracorporeal membrane oxygenation support are warranted.