Can the impact of bed closure in intensive care units be reliably monitored?

Objective: To assess the properties of various indicators aimed at monitoring the impact on the activity and patient outcome of a bed closure in a surgical intensive care unit (ICU). Design: Comparison before and after the intervention. Setting: A surgical ICU at a university hospital. Patients: All patients admitted to the unit over two periods of 10months. Intervention: Closure of one bed out of 17. Measurements and results: Activity and outcome indicators in the ICU and the structures upstream from it (emergency department, operative theater, recovery room) and downstream from it (intermediate care units). After the bed closure, the monthly medians of admitted patients and ICU hospital days increased from 107 (interquartile range 94-112) to 113 (106-121, P=0.07) and from 360 (325-443) to 395 (345-436, P=0.48), respectively, along with the linear trend observed in our institution. All indicators of workload, patient severity, and outcome remained stable except for SAPS II score, emergency admissions, and ICU readmissions, which increased not only transiently but also on a mid-term basis (10months), indicating that the process of patient care delivery was no longer predictable. Conclusions: Health care systems, including ICUs, are extraordinary flexible, and can adapt to multiple external constraints without altering commonly used activity and outcome indicators. It is therefore necessary to set up multiple indicators to be able to reliably monitor the impact of external interventions and intervene rapidly when the system is no longer under contro

Are terminally ill patients dying in the ICU suitable for non-heart beating organ donation?

Objective: To evaluate the feasibility of implementing aprogram of controlled non-heart beating organ donation, in patients undergoing the withdrawal of intensive care treatment. Design and setting: Prospective observational study. Medical and Surgical ICUs in atertiary university hospital. Patients: Consecutive patients younger than 70 years dying in the ICU after treatment withdrawal for dire neurological prognosis. Measurements and results: We analyzed prospectively collected data from the ICU clinical information system. Seventy-three of 516 ICU deaths (13%) were identified, equally distributed among traumatic, stroke, and anoxic brain injury. The management and the course in these three diagnostic categories were similar. All patients underwent withdrawal of mechanical ventilation and half were extubated. Median time to death was of 4.8 h (IQR 1.4-11.5). In 70% of cases the patient received analgesia and 30% sedation. Such treatment was not related to earlier death. Hypotension was observed in 50% of patients during the 30 min preceding cardiac death. Conclusions: With our current management of terminal patients controlled non-heart beating organ procedure may be difficult due to the duration and variability of the dying process. This observation suggests that we can perform better by evaluating this process moreclosel

Blunting the response to endotoxin in healthy subjects: effects of various doses of intravenous fish oil

Objective: To test the dose response effect of infused fish oil (FO) rich in n-3 PUFAs on the inflammatory response to endotoxin (LPS) and on membrane incorporation of fatty acids in healthy subjects. Design: Prospective, sequential investigation comparing three different FO doses. Subjects: Three groups of male subjects aged 26.8±3.2years (BMI 22.5±2.1). Intervention: One of three FO doses (Omegaven®10%) as a slow infusion before LPS: 0.5g/kg 1day before LPS, 0.2g/kg 1day before, or 0.2g/kg 2h before. Measurements and results: Temperature, hemodynamic variables, indirect calorimetry and blood samples (TNF-α, stress hormones) were collected. After LPS temperature, ACTH and TNF-α concentrations increased in the three groups: the responses were significantly blunted (p<0.0001) compared with the control group of the Pluess et al. trial. Cortisol was unchanged. Lowest plasma ACTH, TNF-α and temperature AUC values were observed after a single 0.2g/kg dose of FO. EPA incorporation into platelet membranes was dose-dependent. Conclusions: Having previously shown that the response to LPS was reproducible, this study shows that three FO doses blunted it to various degrees. The 0.2g/kg perfusion immediately before LPS was the most efficient in blunting the responses, suggesting LPS capture in addition to the systemic and membrane effect

Neurally adjusted ventilatory assist (NAVA) improves patient-ventilator interaction during non-invasive ventilation delivered by face mask

Purpose: To determine if, compared to pressure support (PS), neurally adjusted ventilatory assist (NAVA) reduces patient-ventilator asynchrony in intensive care patients undergoing noninvasive ventilation with an oronasal face mask. Methods: In this prospective interventional study we compared patient-ventilator synchrony between PS (with ventilator settings determined by the clinician) and NAVA (with the level set so as to obtain the same maximal airway pressure as in PS). Two 20-min recordings of airway pressure, flow and electrical activity of the diaphragm during PS and NAVA were acquired in a randomized order. Trigger delay (T d), the patient's neural inspiratory time (T in), ventilator pressurization duration (T iv), inspiratory time in excess (T iex), number of asynchrony events per minute and asynchrony index (AI) were determined. Results: The study included 13 patients, six with COPD, and two with mixed pulmonary disease. T d was reduced with NAVA: median 35ms (IQR 31-53ms) versus 181ms (122-208ms); p=0.0002. NAVA reduced both premature and delayed cyclings in the majority of patients, but not the median T iex value. The total number of asynchrony events tended to be reduced with NAVA: 1.0events/min (0.5-3.1events/min) versus 4.4events/min (0.9-12.1events/min); p=0.08. AI was lower with NAVA: 4.9 % (2.5-10.5 %) versus 15.8 % (5.5-49.6 %); p=0.03. During NAVA, there were no ineffective efforts, or late or premature cyclings. PaO2 and PaCO2 were not different between ventilatory modes. Conclusion: Compared to PS, NAVA improved patient ventilator synchrony during noninvasive ventilation by reducing T d and AI. Moreover, with NAVA, ineffective efforts, and late and premature cyclings were absen

Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients

INTRODUCTION: Oxidative stress is involved in the development of secondary tissue damage and organ failure. Micronutrients contributing to the antioxidant (AOX) defense exhibit low plasma levels during critical illness. The aim of this study was to investigate the impact of early AOX micronutrients on clinical outcome in intensive care unit (ICU) patients with conditions characterized by oxidative stress. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled, single-center trial in patients admitted to a university hospital ICU with organ failure after complicated cardiac surgery, major trauma, or subarachnoid hemorrhage. Stratification by diagnosis was performed before randomization. The intervention was intravenous supplements for 5 days (selenium 270 microg, zinc 30 mg, vitamin C 1.1 g, and vitamin B1 100 mg) with a double-loading dose on days 1 and 2 or placebo. RESULTS: Two hundred patients were included (102 AOX and 98 placebo). While age and gender did not differ, brain injury was more severe in the AOX trauma group (P = 0.019). Organ function endpoints did not differ: incidence of acute kidney failure and sequential organ failure assessment score decrease were similar (-3.2 +/- 3.2 versus -4.2 +/- 2.3 over the course of 5 days). Plasma concentrations of selenium, zinc, and glutathione peroxidase, low on admission, increased significantly to within normal values in the AOX group. C-reactive protein decreased faster in the AOX group (P = 0.039). Infectious complications did not differ. Length of hospital stay did not differ (16.5 versus 20 days), being shorter only in surviving AOX trauma patients (-10 days; P = 0.045). CONCLUSION: The AOX intervention did not reduce early organ dysfunction but significantly reduced the inflammatory response in cardiac surgery and trauma patients, which may prove beneficial in conditions with an intense inflammation. TRIALS REGISTRATION: Clinical Trials.gov RCT Register: NCT00515736

Effects of endotoxin on lactate metabolism in humans.

ABSTRACT: INTRODUCTION: Hyperlactatemia represents one prominent component of the metabolic response to sepsis. In critically ill patients, hyperlactatemia is related to the severity of the underlying condition. Both an increased production and a decreased utilization and clearance might be involved in this process, but their relative contribution remains unknown. The present study aimed at assessing systemic and muscle lactate production and systemic lactate clearance in healthy human volunteers, using intravenous endotoxin (LPS) challenge. METHODS: Fourteen healthy male volunteers were enrolled in 2 consecutive studies (n = 6 in trial 1 and n = 8 in trial 2). Each subject took part in one of two investigation days (LPS-day with endotoxin injection and placebo-day with saline injection) separated by one week at least and in a random order. In trial 1, their muscle lactate metabolism was monitored using microdialysis. In trial 2, their systemic lactate metabolism was monitored by means of a constant infusion of exogenous lactate. Energy metabolism was monitored by indirect calorimetry and glucose kinetics was measured with 6,6-H2 glucose. RESULTS: In both trials, LPS increased energy expenditure (p = 0.011), lipid oxidation (p&lt;0.0001), and plasma lactate concentration (p = 0.016). In trial 1, lactate concentration in the muscle microdialysate was higher than in blood, indicating lactate production by muscles. This was, however, similar with and without LPS. In trial 2, calculated systemic lactate production increased after LPS (p = 0.031), while lactate clearance remained unchanged. CONCLUSIONS: LPS administration increases lactatemia by increasing lactate production rather than by decreasing lactate clearance. Muscle is, however, unlikely to be a major contributor to this increase in lactate production. TRIAL REGISTRATION: ClinicalTrials.gov NCT01647997

Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials

INTRODUCTION: Nosocomial pneumonia is a major source of morbidity and mortality after severe burns. Burned patients suffer trace element deficiencies and depressed antioxidant and immune defences. This study aimed at determining the effect of trace element supplementation on nosocomial or intensive care unit (ICU)-acquired pneumonia. METHODS: Two consecutive, randomised, double-blinded, supplementation studies including two homogeneous groups of 41 severely burned patients (20 placebo and 21 intervention) admitted to the burn centre of a university hospital were combined. Intervention consisted of intravenous trace element supplements (copper 2.5 to 3.1 mg/day, selenium 315 to 380 μg/day, and zinc 26.2 to 31.4 mg/day) for 8 to 21 days versus placebo. Endpoints were infections during the first 30 days (predefined criteria for pneumonia, bacteraemia, wound, urine, and other), wound healing, and length of ICU stay. Plasma and skin (study 2) concentrations of selenium and zinc were determined on days 3, 10, and 20. RESULTS: The patients, 42 ± 15 years old, were burned on 46% ± 19% of body surface: the combined characteristics of the patients did not differ between the groups. Plasma trace element concentrations and antioxidative capacity were significantly enhanced with normalisation of plasma selenium, zinc, and glutathione peroxidase concentrations in plasma and skin in the trace element-supplemented group. A significant reduction in number of infections was observed in the supplemented patients, which decreased from 3.5 ± 1.2 to 2.0 ± 1.0 episodes per patient in placebo group (p < 0.001). This was related to a reduction of nosocomial pneumonia, which occurred in 16 (80%) patients versus seven (33%) patients, respectively (p < 0.001), and of ventilator-associated pneumonia from 13 to six episodes, respectively (p = 0.023). CONCLUSION: Enhancing trace element status and antioxidant defences by selenium, zinc, and copper supplementation was associated with a decrease of nosocomial pneumonia in critically ill, severely burned patients

Effect of bicarbonate and lactate buffer on glucose and lactate metabolism during hemodiafiltration in patients with multiple organ failure

Objective: To compare the effects of sodium bicarbonate and lactate for continuous veno-venous hemodiafiltration (CVVHDF) in critically ill patients. Design and settings: Prospective crossed-over controlled trial in the surgical and medical ICUs of a university hospital. Patients: Eight patients with multiple organ dysfunction syndrome (MODS) requiring CVVHDF. Intervention: Each patient received the two buffers in a randomized sequence over two consecutive days. Measurements and results: The following variables were determined: acid-base parameters, lactate production and utilization (13C lactate infusion), glucose turnover (6,62H2-glucose), gas exchange (indirect calorimetry). No side effect was observed during lactate administration. Baseline arterial acid-base variables were equal with the two buffers. Arterial lactate (2.9 versus 1.5mmol/l), glycemia (+18%) and glucose turnover (+23%) were higher in the lactate period. Bicarbonate and glucose losses in CVVHDF were substantial, but not lactate elimination. Infusing 13C lactate increased plasma lactate levels equally with the two buffers. Lactate clearance (7.8±0.8 vs 7.5±0.8ml/kg per min in the bicarbonate and lactate periods) and endogenous production rates (14.0±2.6 vs 13.6±2.6mmol/kg per min) were similar. 13C lactate was used as a metabolic substrate, as shown by 13CO2 excretion. Glycemia and metabolic rate increased significantly and similarly during the two periods during lactate infusion. Conclusion: Lactate was rapidly cleared from the blood of critically ill patients without acute liver failure requiring CVVHDF, being transformed into glucose or oxidized. Lactate did not exert undesirable effects, except moderate hyperglycemia, and achieved comparable effects on acid-base balance to bicarbonat

Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects

Objective: To assess the effects of intravenous fish oil fat emulsion on the metabolic alterations induced by lipopolysaccharide (LPS) challenge in healthy volunteers. Design: Two groups of eight healthy subjects were randomized to receive either two pharmacological doses of intravenous FO fat emulsion or no treatment. The FO group received twice 0.5 g/kg 10% emulsion (Omegaven) 48 and 24 h before investigation. LPS (2 ng/kg) was injected as abolus on the investigation day. Systemic parameters, indirect calorimetry, heart rate variability, and platelet membrane phospholipid composition were measured. Results: Basal EPA and DHA content in platelet phospholipids was low (0.28% and 2.54%, respectively) and increased significantly after FO to 1.68% and 3.32%. LPS induced reproducible effects in all subjects. Fever was higher in the FO group than in controls; the difference was significant from t 120 until t 360. FO blunted the neuroendocrine response: the rise in plasma norepinephrine was sevenfold lower at t 120 while the ACTH peak was fourfold lower. Tumor necrosis factor α was significantly lower between t 360 and t 180 in the FO group. Conclusions: Two doses of intravenous FO fat emulsion modified the phospholipid composition of platelets in healthy subjects. FO blunted fever and increased the neuroendocrine and the inflammatory responses to LP