David V. Tuxen

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.

Effects of gastric alkalization on bacterial colonization in critically ill patients.

Gastric alkalization of critically ill patients is associated with bacterial and fungal overgrowth in gastric contents. We studied the incidence of gastric colonization and its relation to other infections and antibiotic therapy in 25 critically ill ICU patients. All patients received 12-h NG Mylanta II and 15 received an H2-receptor antagonist. All patients had bacterial colonization of NG contents within 4 days of ICU admission and 10 had Candida colonization within 8 days. There were 70 NG isolates and the same isolates were found in tracheobronchial secretions (n = 46), blood (n = 4), urine (n = 4), and wounds (n = 8). Tracheobronchial colonization was preceded by NG colonization with the same organism in 12 instances (11 patients), was concurrent with NG colonization in 20 instances (14 patients), was followed by NG colonization in 14 instances (11 patients), and had no similar NG isolate in 18 instances (11 patients). NG culture of the same organism preceded four of eight positive blood cultures. In 35 of 70 NG isolates and five of 11 subsequent tracheobronchial isolates, colonization occurred despite concurrent appropriate antibiotics. We conclude that colonization of alkalinized NG contents is universal, is a common source of infection in other areas, and is not prevented by systemic antibiotic therapy. Local antibiotic therapy may be important in controlling this important source of infection.

A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome

IntroductionTidal volume and plateau pressure minimisation are the standard components of a protective lung ventilation strategy for patients with acute respiratory distress syndrome (ARDS). Open lung strategies, including higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres to date have not proven efficacious. This study examines the effectiveness and safety of a novel open lung strategy, which includes permissive hypercapnia, staircase recruitment manoeuvres (SRM) and low airway pressure with PEEP titration.MethodTwenty ARDS patients were randomised to treatment or ARDSnet control ventilation strategies. The treatment group received SRM with decremental PEEP titration and targeted plateau pressure < 30 cm H2O. Gas exchange and lung compliance were measured daily for 7 days and plasma cytokines in the first 24 hours and on days 1, 3, 5 and 7 (mean ± SE). Duration of ventilation, ICU stay and hospital stay (median and interquartile range) and hospital survival were determined.ResultsThere were significant overall differences between groups when considering plasma IL-8 and TNF-α. For plasma IL-8, the control group was 41% higher than the treatment group over the seven-day period (ratio 1.41 (1.11 to 1.79), P = 0.01), while for TNF-α the control group was 20% higher over the seven-day period (ratio 1.20 (1.01 to 1.42) P = 0.05). PaO2/FIO2 (204 ± 9 versus 165 ± 9 mmHg, P = 0.005) and static lung compliance (49.1 ± 2.9 versus 33.7 ± 2.7 mls/cm H2O, P < 0.001) were higher in the treatment group than the control group over seven days. There was no difference in duration of ventilation (180 (87 to 298) versus 341 (131 to 351) hrs, P = 0.13), duration of ICU stay (9.9 (5.6 to 14.8) versus 16.0 (8.1 to 19.3) days, P = 0.19) and duration of hospital stay (17.9 (13.7 to 34.5) versus 24.7 (20.5 to 39.8) days, P = 0.16) between the treatment and control groups.ConclusionsThis open lung strategy was associated with greater amelioration in some systemic cytokines, improved oxygenation and lung compliance over seven days. A larger trial powered to examine clinically-meaningful outcomes is warranted.Trial registrationACTRN12607000465459

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.

Long-term quality of life in patients with acute respiratory distress syndrome requiring extracorporeal membrane oxygenation for refractory hypoxaemia

IntroductionThe purpose of the study was to assess the long term outcome and quality of life of patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia.MethodsA retrospective observational study with prospective health related quality of life (HRQoL) assessment was conducted in ARDS patients who had ECMO as a rescue therapy for reversible refractory hypoxemia from January 2009 until April 2011 in a tertiary Australian centre. Survival and long-term quality of life assessment, using the Short-Form 36 (SF-36) and the EuroQol health related quality of life questionnaire (EQ5D) were assessed and compared to international data from other research groups.ResultsTwenty-one patients (mean age 36.3 years) with ARDS receiving ECMO for refractory hypoxemia were studied. Eighteen (86%) patients were retrieved from external intensive care units (ICUs) by a dedicated ECMO retrieval team. Eleven (55%) had H1N1 influenza A-associated pneumonitis. Eighteen (86%) patients survived to hospital discharge. Of the 18 survivors, ten (56%) were discharged to other hospitals and 8 (44%) were discharged directly home. Sequelae and health related quality of life were evaluated for 15 of the 18 (71%) long-term survivors (assessment at median 8 months). Mean SF-36 scores were significantly lower across all domains compared to age and sex matched Australian norms. Mean SF-36 scores were lower (minimum important difference at least 5 points) than previously described ARDS survivors in the domains of general health, mental health, vitality and social function. One patient had long-term disability as a result of ICU acquired weakness. Only 26% of survivors had returned to previous work levels at the time of follow-up.ConclusionsThis ARDS cohort had a high survival rate (86%) after use of ECMO support for reversible refractory hypoxemia. Long term survivors had similar physical health but decreased mental health, general health, vitality and social function compared to other ARDS survivors and an unexpectedly poor return to work.

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.

A Positive Response to a Recruitment Maneuver With PEEP Titration in Patients With ARDS, Regardless of Transient Oxygen Desaturation During the Maneuver:

Recruitment maneuvers (RMs) can expand collapsed alveoli in ventilated patients. The optimal method for delivering RMs is unknown. Purpose: To evaluate the safety and the respiratory and hemodynamic effects of a staircase recruitment maneuver (SRM) with decremental positive end expiratory pressure (PEEP) titration and the consequences of desaturation during the SRM in patients with early acute lung injury (ALI). Methods: In total, 20 consecutive patients with early ALI were enrolled and received an SRM. Patients were given 15 ± 3 cm H2O pressure-controlled ventilation. Positive end expiratory pressure was increased from baseline (range 10-18) to 20, 30, and 40 cm H2O every 2 minutes to achieve maximum alveolar pressure of 55 ± 3 cm H2O, then decreased at 3-minute intervals to 25, 22.5, 20, 17.5, and 15 cm H2O until a decrease of 1% to 2% oxygen saturation from maximum was detected. Positive end expiratory pressure was left at the level where the fall in oxygen saturation occurred. Standard respiratory and circulatory variables, arterial and central venous gases were measured before, during, and after the SRM. Results: There were significant improvements in shunt fraction (36.3% ± 10% to 26.4% ± 14%, P < .001), oxygen saturation (93.4% ± 2% to 96.8% ± 3%, P = .007), partial pressure of oxygen, arterial (PaO2)/fraction of inspired oxygen ([FIO2]; 150 ± 42 to 227 ± 100, P = .004), lung compliance (33.9 ± 9.1 to 40.1 ± 11.4 mL/cm H2O, P < .01), and chest x-ray (CXR) after the SRM. Briefly, 80% of the patients responded and the response was maintained at 1 hour. In total, 8 patients desaturated 6.1% ± 2.8% in SaO2 during the SRM but 5 of those improved SaO2 relative to baseline by the end of the SRM. Conclusions: In all, 80% of the patients with early ALI responded to the SRM with decremental PEEP titration. Desaturation during the SRM did not indicate a failed response 1 hour later.

Whole lung pulmonary angiography in the intensive care unit with two portable chest X-rays

Suspected massive pulmonary embolism requires urgent, accurate diagnosis. We describe a technique for pulmonary angiography in the ICU. Four patients admitted with suspected pulmonary embolism had fulminating cardiorespiratory failure with support requirements precluding transfer. Each patient had a flow-directed pulmonary angiography catheter inserted into the pulmonary artery. In two catheter positions, 25 ml of iopamidol 612 mg/ml was delivered from a portable angiographic injector at a flow of 20 ml/sec. A portable x-ray was taken immediately before completion of syringe excursion. Major central pulmonary emboli were seen in three patients and a negative angiogram was obtained on the fourth. Two of the three positive diagnoses were confirmed at pulmonary embolectomy. The negative diagnosis was confirmed at autopsy. Pulmonary angiography via a flow-directed catheter enabled precise and rapid diagnosis of pulmonary embolism in patients too ill to transfer for formal angiography.