Faculty Bibliography

Plasma clearance of D-sorbitol, a nontoxic polyol, occurs predominantly in the liver and has been used to measure functional liver blood flow after bolus and steady- state intravenous administration. However, it is not known which of these two administration methods is superior. Therefore, plasma D-sorbitol clearance was studied in an animal model both after a bolus dose and under steady-state (SS) conditions and compared directly with liver blood flow, under normal conditions, and after the induction of endotoxin (LPS) sepsis. Adult male Wistar rats (526 +/- 38 g body wt; n = 27) were anesthetized and mechanically ventilated. Hemodynamics, hepatic arterial flow, and portal venous flow were measured. Two groups were studied, namely healthy animals that served as controls and a sepsis group that received 5 mg/kg LPS intravenously (Escherichia coli O127:B8). Each animal received either a SS infusion (0.1 mg/100 g body wt per min) or a bolus (3 mg/100 g body wt) of a 5% D-sorbitol solution intravenously in a randomized order. After the initial measurements and a 60-min pause time in between (T(1/2,sorbitol) = 9 min), a crossover was done. The hepatic clearance of D-sorbitol in the control group showed a good correlation between bolus and SS (Spearman's r = 0.7681, P = 0.0004), and both techniques correlated well with total liver blood flow (TLBF) (r = 0.7239, P = 0.0023 and r = 0.7226, P = 0.0023, respectively). Also in the sepsis group there was a good correlation between bolus and SS sorbitol clearance (r = 0.6655, P = 0.0182). In the sepsis group, only the SS clearance correlated with TLBF (r = 0.6434, P = 0.024). In conclusion, in normal and under septic conditions, hepatic clearance of D-sorbitol either by bolus or a SS infusion is comparable. In healthy animals, this also correlated well with TLBF but not in septic conditions. However, this is expected because of the changes in the liver microcirculation, shunting, and decreased hepatocyte function in sepsis.

INTRODUCTION: Hospitals are increasingly forced to consider the economics of technology use. We estimated the incremental cost-consequences of remifentanil-based analgo-sedation (RS) vs. conventional analgesia and sedation (CS) in patients requiring mechanical ventilation (MV) in the intensive care unit (ICU), using a modelling approach. METHODS: A Markov model was developed to describe patient flow in the ICU. The hourly probabilities to move from one state to another were derived from UltiSAFE, a Dutch clinical study involving ICU patients with an expected MV-time of two to three days requiring analgesia and sedation. Study medication was either: CS (morphine or fentanyl combined with propofol, midazolam or lorazepam) or: RS (remifentanil, combined with propofol when required). Study drug costs were derived from the trial, whereas all other ICU costs were estimated separately in a Dutch micro-costing study. All costs were measured from the hospital perspective (price level of 2006). Patients were followed in the model for 28 days. We also studied the sub-population where weaning had started within 72 hours. RESULTS: The average total 28-day costs were euro15,626 with RS versus euro17,100 with CS, meaning a difference in costs of euro1474 (95% CI -2163, 5110). The average length-of-stay (LOS) in the ICU was 7.6 days in the RS group versus 8.5 days in the CS group (difference 1.0, 95% CI -0.7, 2.6), while the average MV time was 5.0 days for RS versus 6.0 days for CS. Similar differences were found in the subgroup analysis. CONCLUSIONS: Compared to CS, RS significantly decreases the overall costs in the ICU. TRIAL REGISTRATION: Clinicaltrials.gov NCT00158873.

INTRODUCTION: As it becomes clear that mechanical ventilation can exaggerate lung injury, individual titration of ventilator settings is of special interest. Electrical impedance tomography (EIT) has been proposed as a bedside, regional monitoring tool to guide these settings. In the present study we evaluate the use of ventilation distribution change maps (DeltafEIT maps) in intensive care unit (ICU) patients with or without lung disorders during a standardized decremental positive end-expiratory pressure (PEEP) trial. METHODS: Functional EIT (fEIT) images and PaO2/FiO2 ratios were obtained at four PEEP levels (15 to 10 to 5 to 0 cm H2O) in 14 ICU patients with or without lung disorders. Patients were pressure-controlled ventilated with constant driving pressure. fEIT images made before each reduction in PEEP were subtracted from those recorded after each PEEP step to evaluate regional increase/decrease in tidal impedance in each EIT pixel (DeltafEIT maps). RESULTS: The response of regional tidal impedance to PEEP showed a significant difference from 15 to 10 (P = 0.002) and from 10 to 5 (P = 0.001) between patients with and without lung disorders. Tidal impedance increased only in the non-dependent parts in patients without lung disorders after decreasing PEEP from 15 to 10 cm H2O, whereas it decreased at the other PEEP steps in both groups. CONCLUSIONS: During a decremental PEEP trial in ICU patients, EIT measurements performed just above the diaphragm clearly visualize improvement and loss of ventilation in dependent and non-dependent parts, at the bedside in the individual patient.

OBJECTIVE: To decide whether the use of blood lactate monitoring in critical care practice is appropriate. We performed a systematic health technology assessment as blood lactate monitoring has been implemented widely but its clinical value in critically ill patients has never been evaluated properly. DATA SOURCE: PubMed, other databases, and citation review. STUDY SELECTION: We searched for lactate combined with critically ill patients as the target patient population. Two reviewers independently selected studies based on relevance for the following questions: Does lactate measurement: 1) perform well in a laboratory setting? 2) provide information in a number of clinical situations? 3) relate to metabolic acidosis? 4) increase workers' confidence? 5) alter therapeutic decisions? 6) result in benefit to patients? 7) result in similar benefits in your own setting? 8) result in benefits which are worth the extra costs? DATA EXTRACTION AND SYNTHESIS: We concluded that blood lactate measurement in critically ill patients: 1) is accurate in terms of measurement technique but adequate understanding of the (an)aerobic etiology is required for its correct interpretation; 2) provides not only diagnostic but also important prognostic information; 3) should be measured directly instead of estimated from other acid-base variables; 4) has an unknown effect on healthcare workers' confidence; 5) can alter therapeutic decisions; 6) could potentially improve patient outcome when combined with a treatment algorithm to optimize oxygen delivery, but this has only been shown indirectly; 7) is likely to have similar benefits in critical care settings worldwide; and 8) has an unknown cost-effectiveness. CONCLUSIONS: The use of blood lactate monitoring has a place in risk-stratification in critically ill patients, but it is unknown whether the routine use of lactate as a resuscitation end point improves outcome. This warrants randomized controlled studies on the efficacy of lactate-directed therapy.

PURPOSE: Monitoring end-expiratory lung volume (EELV) is a valuable tool to optimize respiratory settings that could be of particular importance in mechanically ventilated pediatric patients. We evaluated the feasibility and precision of an intensive care unit (ICU) ventilator with an in-built nitrogen washout/washin technique in mechanically ventilated pediatric patients. METHODS: Duplicate EELV measurements were performed in 30 patients between 5 kg and 43 kg after cardiac surgery (age, median + range: 26, 3-141 months). All measurements were taken during pressure-controlled ventilation at 0 cm H(2)O of positive end-expiratory pressure (PEEP). RESULTS: Linear regression between duplicate measurements was excellent (R (2) = 0.99). Also, there was good agreement between duplicate measurements, bias +/- SD: -0.3% (-1.5 mL) +/- 5.9% (19.2 mL). Mean EELV +/- SD was 19.6 +/- 5.1 mL/kg at 0 cm H(2)O PEEP. EELV correlated with age (p < 0.001, r = 0.92, R (2) = 0.78), body weight (p < 0.001, r = 0.91, R (2) = 0.82) and height (p < 0.001, r = 0.94, R (2) = 0.75). CONCLUSION: This ICU ventilator with an in-built nitrogen washout/washin EELV technique can measure EELV with precision, and can easily be used for mechanically ventilated pediatric patients.

PURPOSE OF REVIEW: Traditionally, the assessment of critical care has focused largely on mortality. However, in the last few years, there is more attention on the quality of survival. Health-related quality of life (HRQOL) is an important issue for both patients and family. The purpose of this review is to describe HRQOL scoring in critically ill patients and to discuss the clinical impact on HRQOL. RECENT FINDINGS: Studies on the effect of critical illness on HRQOL show contradicting results. Several studies found that HRQOL at the time of discharge from hospital was impaired and that a gradual improvement occurred during follow-up, in some cases to preadmission hospital levels. Others show a full recovery to preadmission HRQOL. SUMMARY: In this article, we reviewed the methods and description of measurement instruments used in critically ill patients. The most recently used instruments to measure HRQOL, how to score HRQOL before ICU admission and the impact of critical illness on HRQOL are discussed. Assessment of HRQOL can improve the answers given by critical care physicians and nurses about the prospects of their patients. To get insights in these issues regarding the impact of ICU treatment, we should incorporate not only short-term outcomes, for example length of stay and mortality, but also HRQOL.

OBJECTIVES: To evaluate whether the level and duration of increased blood lactate levels are associated with daily Sequential Organ Failure Assessment (SOFA) scores and organ subscores and to evaluate these associations during the early and late phases of the intensive care unit stay. DESIGN: Retrospective observational study. SETTING: Mixed intensive care unit of a university hospital. PATIENTS: 134 heterogeneous intensive care unit patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We calculated the area under the lactate curve above 2.0 mmol/L (lactateAUC>2). Daily SOFA scores were collected during the first 28 days of intensive care unit stay to calculate initial (day 1), maximal, total and mean scores. Daily lactateAUC>2 values were related to both daily SOFA scores and organ subscores using mixed-model analysis of variance. This was also done separately during the early (<2.75 days) and late (>2.75 days) phase of the intensive care unit stay.Compared with normolactatemic patients (n = 78), all median SOFA variables were higher in patients with hyperlactatemia (n = 56) (initial SOFA: 9 [interquartile range 4-12] vs. 4 [2-7]; maximal SOFA: 10 [5-13] vs. 5 [2-9]; total SOFA: 28 [10-70] vs. 9 [3-41]; mean SOFA: 7 [4-10] vs. 4 [2-6], all p < .001). The overall relationship between daily lactateAUC>2 and daily SOFA was an increase of 0.62 SOFA-points per 1 day.mmol/L of lactateAUC>2 (95% confidence interval, 0.41-0.81, p < .00001). During early intensive care unit stay, the relationship between lactateAUC>2 and SOFA was 1.01 (95% confidence interval, 0.53-1.50, p < .0005), and during late intensive care unit stay, this was reduced to 0.50 (95% confidence interval, 0.28-0.72, p < .0005). Respiratory (0.30, 0.22-0.38, p < .001) and coagulation (0.13, 0.09-0.18, p < .001) subscores were most strongly associated with lactateAUC>2. CONCLUSIONS: Blood lactate levels were strongly related to SOFA scores. This relationship was stronger during the early phase of intensive care unit stay, which provides additional indirect support for early resuscitation to prevent organ failure. The results confirm that hyperlactatemia can be considered as a warning signal for organ failure.

PURPOSE: To study and compare the relationship between end-expiratory lung volume (EELV) and changes in end-expiratory lung impedance (EELI) measured with electrical impedance tomography (EIT) at the basal part of the lung at different PEEP levels in a mixed ICU population. METHODS: End-expiratory lung volume, EELI and tidal impedance variation were determined at four PEEP levels (15-10-5-0 cm H2O) in 25 ventilated ICU patients. The tidal impedance variation and tidal volume at 5 cm H2O PEEP were used to calculate change in impedance per ml; this ratio was then used to calculate change in lung volume from change in EELI. To evaluate repeatability, EELV was measured in quadruplicate in five additional patients. RESULTS: There was a significant but relatively low correlation (r = 0.79; R2 = 0.62) and moderate agreement (bias 194 ml, SD 323 ml) between DeltaEELV and change in lung volume calculated from the DeltaEELI. The ratio of tidal impedance variation and tidal volume differed between patients and also varied at different PEEP levels. Good agreement was found between repeated EELV measurements and washin/washout of a simulated nitrogen washout technique. CONCLUSION: During a PEEP trial, the assumption of a linear relationship between change in global tidal impedance and tidal volume cannot be used to calculate EELV when impedance is measured at only one thoracic level just above the diaphragm.