Faculty Bibliography

A growing body of evidence exists associating depressed microcirculatory function and morbidity and mortality in a wide array of clinical scenarios. It has been suggested that volume replacement therapy using fluids and/or blood in combination with vasoactive agents to modulate macro- and microvascular perfusion might be essential for resuscitation of severely septic patients. Even after interventions effectively optimizing macrocirculatory hemodynamics, however, high mortality rates still persist in critically ill and especially in septic patients. Therefore, rather than limiting therapy to macrocirculatory targets alone, microcirculatory targets could be incorporated to potentially reduce mortality rates in these critically ill patients. In the present review we first provide a brief history of clinical imaging of the microcirculation and describe how microcirculatory imaging has been of prognostic value in intensive care patients. We then give an overview of therapies potentially improving the microcirculation in critically ill patients and propose a clinical trial aimed at demonstrating that therapy targeting improvement of the microcirculation results in improved organ function in patients with severe sepsis and septic shock. We end with some recent technological advances in clinical microcirculatory image acquisition and analysis.

Acute kidney injury (AKI) is strongly associated with increased morbidity and mortality in critically ill patients. Efforts to change its clinical course have failed because clinically available therapeutic measures are currently lacking, and early detection is impossible with serum creatinine (SCr). The demand for earlier markers has prompted the discovery of several candidates to serve this purpose. In this paper, we review available biomarker studies on the early predictive performance in developing AKI in adult critically ill patients. We make an effort to present the results from the perspective of possible clinical utility.

PURPOSE: Near-infrared spectroscopy has been used as a noninvasive monitoring tool for tissue oxygen saturation (StO(2)) in acutely ill patients. This study aimed to investigate whether local vasoconstriction induced by body surface cooling significantly influences thenar StO(2) as measured by InSpectra model 650. METHODS: Eight healthy individuals (age 26 +/- 6 years) participated in the study. Using a cooling blanket, we aimed to cool the entire body surface to induce vasoconstriction in the skin without any changes in central temperature. Thenar StO(2) was noninvasively measured during a 3-min vascular occlusion test using InSpectra model 650 with a 15-mm probe. Measurements were analyzed for resting StO(2) values, rate of StO(2) desaturation (RdecStO(2), %/min), and rate of StO(2) recovery (RincStO(2), %/s) before, during, and after skin cooling. Measurements also included heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), stroke volume (SV), capillary refill time (CRT), forearm-to-fingertip skin-temperature gradient (Tskin-diff), perfusion index (PI), and tissue hemoglobin index (THI). RESULTS: In all subjects MAP, CO, SV, and core temperature did not change during the procedure. Skin cooling resulted in a significant decrease in StO(2) from 82% (80-87) to 72% (70-77) (P < 0.05) and in RincStO(2) from 3.0%/s (2.8-3.3) to 1.7%/s (1.1-2.0) (P < 0.05). Similar changes in CRT, Tskin-diff, and PI were also observed: from 2.5 s (2.0-3.0) to 8.5 s (7.2-11.0) (P < 0.05), from 1.0 degrees C (-1.6-1.8) to 3.1 degrees C (1.8-4.3) (P < 0.05), and from 10.0% (9.1-11.7) to 2.5% (2.0-3.8), respectively. The THI values did not change significantly. CONCLUSION: Peripheral vasoconstriction due to body surface cooling could significantly influence noninvasive measurements of thenar StO(2) using InSpectra model 650 with 15-mm probe spacing.

OBJECTIVE: To determine the incidence of withdrawal of life-sustaining treatment in various groups of patients in a mixed intensive care unit (ICU). DESIGN: Observational retrospective. SETTING: University hospital mixed medical, neurological, neurosurgical and surgical ICU. PATIENTS: All patients admitted to the ICU between 1 November 2006, and 31 October 2007. RESULTS: 1,353 Patients were admitted to our ICU between 1 November 2006, and 31 October 2007. During this period, 218 (16.1%) patients died in the ICU, 10 of which were excluded for further analysis. In 174 (83.7%) of the remaining 208 patients, life-sustaining treatment was withdrawn. Severe CNS injury was in 86 patients (49.4%) being the reason for withdrawal of treatment, followed by MODS in 67 patients (38.5%). Notably, treatment was withdrawn in almost all patients (95%) who died of CNS failure. Patients who died in the ICU were significantly older, more often admitted for medical than surgical reasons, and had higher SOFA and APACHE II scores compared with those who survived their ICU stay. Also, SOFA scores before discharge/death were significantly different from admission scores. Of the 1,135 patients who survived their ICU stay, only 51 patients (4.5%) died within 28 days after ICU discharge. CONCLUSIONS: In 83, 7% of patients who die in the mixed ICU life-sustaining treatment is withdrawn. Severe cerebral damage was the leading reason to withdraw life-sustaining treatment.

OBJECTIVES: The objective of the present study was to measure and compare the direct costs of intensive care unit (ICU) days at seven ICU departments in Germany, Italy, the Netherlands, and the United Kingdom by means of a standardized costing methodology. METHODS: A retrospective cost analysis of ICU patients was performed from the hospital's perspective. The standardized costing methodology was developed on the basis of the availability of data at the seven ICU departments. It entailed the application of the bottom-up approach for "hotel and nutrition" and the top-down approach for "diagnostics," "consumables," and "labor." RESULTS: Direct costs per ICU day ranged from euro1168 to euro2025. Even though the distribution of costs varied by cost component, labor was the most important cost driver at all departments. The costs for "labor" amounted to euro1629 at department G but were fairly similar at the other departments (euro711 +/- 115). CONCLUSIONS: Direct costs of ICU days vary widely between the seven departments. Our standardized costing methodology could serve as a valuable instrument to compare actual cost differences, such as those resulting from differences in patient case-mix.

RATIONALE: Life and death triage decisions are made daily by intensive care unit physicians. Admission to an intensive care unit is denied when intensive care unit resources are constrained, especially for the elderly. OBJECTIVE: To determine the effect of intensive care unit triage decisions on mortality and intensive care unit benefit, specifically for elderly patients. DESIGN: Prospective, observational study of triage decisions from September 2003 until March 2005. SETTING: Eleven intensive care units in seven European countries. PATIENTS: All patients >18 yrs with an explicit request for intensive care unit admission. INTERVENTIONS: Admission or rejection to intensive care unit. MEASUREMENTS AND MAIN RESULTS: Demographic, clinical, hospital, physiologic variables, and 28-day mortality were obtained on consecutive patients. There were 8,472 triages in 6,796 patients, 5,602 (82%) were accepted to the intensive care unit, 1,194 (18%) rejected; 3,795 (49%) were >/= 65 yrs. Refusal rate increased with increasing patient age (18-44: 11%; 45-64: 15%; 65-74: 18%; 75-84: 23%; >84: 36%). Mortality was higher for older patients (18-44: 11%; 45-64: 21%; 65-74: 29%; 75-84: 37%; >84: 48%). Differences between mortalities of accepted vs. rejected patients, however, were greatest for older patients (18-44: 10.2% vs. 12.5%; 45-64: 21.2% vs. 22.3%; 65-74: 27.9% vs. 34.6%; 75-84: 35.5% vs. 40.4%; >84: 41.5% vs. 58.5%). Logistic regression showed a greater mortality reduction for accepted vs. rejected patients corrected for disease severity for elderly patients (age >65 [odds ratio 0.65, 95% confidence interval 0.55-0.78, p < .0001]) than younger patients (age <65 [odds ratio 0.74, 95% confidence interval 0.57-0.97, p = .01]). CONCLUSIONS: Despite the fact that elderly patients have more intensive care unit rejections than younger patients and have a higher mortality when admitted, the mortality benefit appears greater for the elderly. Physicians should consider changing their intensive care unit triage practices for the elderly.

OBJECTIVE: Life and death triage decisions are made daily by intensive care unit physicians. Scoring systems have been developed for prognosticating intensive care unit mortality but none for intensive care unit triage. The objective of this study was to develop an intensive care unit triage decision rule based on 28-day mortality rates of admitted and refused patients. DESIGN: Prospective, observational study of triage decisions from September 2003 until March 2005. SETTING: Eleven intensive care units in seven European countries. PATIENTS: All patients >18 yrs with a request for intensive care unit admission. INTERVENTIONS: Admission or rejection to an intensive care unit. MEASUREMENTS AND MAIN RESULTS: Clinical, laboratory, and physiological variables and data from severity scores were collected. Separate scores for accepted and rejected patients with 28-day mortality end point were built. Values for variables were grouped into categories determined by the locally weighted least squares graphical method applied to the logit of the mortality and by univariate logistic regressions for reducing candidates for the score. Multivariate logistic regression was used to construct the final score. Cutoff values for 99.5% specificity were determined. Of 6796 patients, 5602 were admitted and 1194 rejected. The initial refusal score included age, diagnosis, systolic blood pressure, pulse, respirations, creatinine, bilirubin, PaO2, bicarbonate, albumin, use of vasopressors, Glasgow Coma Scale score, Karnofsky Scale, operative status and chronic disorder, and the initial refusal receiver operating characteristics were area under the curve 0.77 (95% confidence interval 0.76-0.79). The final triage score included age, diagnosis, creatinine, white blood cells, platelets, albumin, use of vasopressors, Glasgow Coma Scale score, Karnofsky Scale, operative status and chronic disorder, and the final score receiver operating characteristics were area under the curve 0.83 (95% confidence interval 0.80-0.86). Patients with initial refusal scores >173.5 or final triage scores = 0 should be rejected. CONCLUSIONS: The initial refusal score and final triage score provide objective data for rejecting patients that will die even if admitted to the intensive care unit and survive if refused intensive care unit admission.

OBJECTIVE: The ability to predict the time of death after withdrawal of life support is of specific interest for organ donation after cardiac death. We aimed to externally validate a previously developed model to predict the probability of death within the time constraint of 60 mins after withdrawal of life-sustaining measures. DESIGN: The probability to die within 60 mins for each patient in this validation sample was calculated based on the model developed by Yee et al, which includes four variables (absent corneal reflex, absent cough reflex, extensor or absent motor response, and an oxygenation index >4.2). Analyses included logistic regression modeling with bootstrapping to adjust for overoptimism. Performance was assessed by calibration (agreement between observed and predicted outcomes) and discrimination (distinction of those patients who die within 60 mins from those who do not, expressed by the area under the receiver operating characteristic curve). SETTING: Mixed intensive care unit in The Netherlands. PATIENTS: We analyzed data from 152 patients who died as a result of a neurologic condition between 2007 and 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 82 patients had sufficient data. Fifty (61%) died within 60 mins. Univariable and multivariable odds ratios of the predictors were very similar between the development and validation sample. The prediction model showed good discrimination with an area under the receiver operating characteristic curve of 0.75 (95% confidence interval [CI] 0.63-0.87) but calibration was modest. The mean predicted probability was 80%, overestimating the 61% overall observed risk of death within 60 mins. Modeling oxygenation index as a linear term led to an improved version of the Mayo NICU model. (area under the receiver operating characteristic curve [95% CI] = 0.774 [0.69-0.90], bootstrap-validated area under the receiver operating characteristic curve [95% CI] = 0.74 [0.66-0.87]). CONCLUSIONS: The model discriminated well between patients who died within 60 mins after withdrawal of life support and those who did not. Further prospective validation is needed.

There are relatively few institutions that have developed clinical data warehouses, containing patient data from the point of care. Because of the various care practices, data types and definitions, and the perceived incompleteness of clinical information systems, the development of a clinical data warehouse is a challenge. In order to deal with managerial and clinical information needs, as well as educational and research aims that are important in the setting of a university hospital, Erasmus Medical Center Rotterdam, The Netherlands, developed a data warehouse incrementally. In this paper we report on the in-house development of an integral part of the data warehouse specifically for the intensive care units (ICU-DWH). It was modeled using Atos Origin Metadata Frame method. The paper describes the methodology, the development process and the content of the ICU-DWH, and discusses the need for (clinical) data warehouses in intensive care.

Objective. Sublingual microcirculatory alterations are associated with an adverse prognosis in several critical illness subgroups. Up to now, single-center studies have reported on sublingual microcirculatory alterations in ICU patient subgroups, but an extensive evaluation of the prevalence of these alterations is lacking. We present the study design of an international multicenter observational study to investigate the prevalence of microcirculatory alterations in critically ill: the Microcirculatory Shock Occurrence in Acutely ill Patients (microSOAP). Methods. 36 ICU's worldwide have participated in this study aiming for inclusion of over 500 evaluable patients. To enable communication and data collection, a website, an Open Clinica 3.0 database, and image uploading software have been designed. A one-session assessment of the sublingual microcirculation using Sidestream Dark Field imaging and data collection on patient characteristics has been performed in every ICU patient >18 years, regardless of underlying disease. Statistical analysis will provide insight in the prevalence and severity of sublingual alterations, its relation to systemic hemodynamic variables, disease, therapy, and outcome. Conclusion. This study will be the largest microcirculation study ever performed. It is expected that this study will also establish a basis for future studies related to the microcirculation in critically ill.