Faculty Bibliography

BACKGROUND: Sepsis and subsequent multiple-organ failure are the predominant causes of late mortality in trauma patients. Susceptibility and response to infection is, in part, heritable. Single-nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) and cluster of differentiation 14 (CD14) genes of innate immunity may play a key role. The aim of this study was to assess if SNPs in TLR/CD14 predisposed trauma patients to infection. METHODS: A prospective cohort of trauma patients (age 18-80 years; injury severity score [ISS] >/= 16) admitted to a Level I trauma center between January 2008 and April 2011 was genotyped for SNPs in TLR2 (T-16934A and R753Q), TLR4 (D299G and T399I), TLR9 (T-1486C and T-1237C), and CD14 (C-159T) using high-resolution melting analysis. Association of genotype with prevalence of positive culture findings (gram positive, gram negative, fungi), systemic inflammatory response syndrome (SIRS), sepsis, septic shock, and mortality was tested with chi(2) and logistic regression analysis. RESULTS: Genotyping was performed for 219 patients, of whom 51% developed positive culture findings in sputum, wounds, blood, or urine. SIRS developed in 64%, sepsis in 36%, and septic shock in 17%. The TLR2 T-16934A TA genotype increased the risk of a gram-positive infection (odds ratio, 2.816; 95% confidence interval, 1.249-6.348; p = 0.013) and SIRS (odds ratio, 2.386; 95% confidence interval, 1.011-5.632; p = 0.047). Trends were noted for TLR9 and CD14 SNPs but did not reach statistical significance. Sepsis and septic shock were unrelated to any of the SNPs studied. CONCLUSION: Aberrant functioning of the TLR/CD14 pathway of innate immunity changes the risk of infectious complications in severely injured trauma patients. Of the seven SNPs studied, the TLR2 T-16934A increased the risk, the TLR9 T-1486C SNPs may decrease the risk, and TLR4 variation seemed unrelated to outcome. Early genotyping may prove to be helpful in the future in identifying polytraumatized patients at risk for infectious outcome. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level II.

BACKGROUND: In healthy volunteers, we investigated the ability of the pulse oximeter-derived peripheral perfusion index (PPI) to detect progressive reductions in central blood volume. METHODS: Twenty-five awake, spontaneously breathing, healthy male volunteers were subjected to progressive reductions in central blood volume by inducing stepwise lower body negative pressure (LBNP) with 20 mm Hg for 5 minutes per step, from 0 to -20, -40, -60, and back to 0 mm Hg. Throughout the procedure, stroke volume (SV), heart rate (HR), and mean arterial blood pressure were recorded using volume-clamp finger plethysmography. Assessment of the PPI was done by pulse oximetry. Additionally, the forearm-to-fingertip skin-temperature gradient was measured. Data are presented as mean+/-SE. PPI underwent log transformation and is presented as median (25th-75th). RESULTS: Of the 25 subjects, one did not complete the study because of cardiovascular collapse. After the first LBNP step (-20 mm Hg), PPI decreased from 2.2 (1.6-3.3) to 1.2 (0.8-1.6) (P=0.007) and SV decreased from 116+/-3.0 mL to 104+/-2.6 mL (P=0.02). The magnitude of the PPI decrease (41%+/-6.0%) was statistically different from that observed for SV (9%+/-1.3%) and HR (3%+/-1.9%). During progression of LBNP, SV decreased and HR increased progressively with the increased applied negative pressure, whereas the PPI remained low throughout the remainder of the protocol and returned to baseline values when LBNP was released. At -60 mm Hg LBNP, SV decreased and HR increased by 36%+/-0.9% and 33%+/-2.4% from baseline, respectively. Mean arterial blood pressure remained in the same range throughout the experiment. CONCLUSIONS: These results indicate that the pulse oximeter-derived PPI may be a valuable adjunct diagnostic tool to detect early clinically significant central hypovolemia, before the onset of cardiovascular decompensation in healthy volunteers.

OBJECT: The goal of awake neurosurgery is to maximize resection of brain lesions with minimal injury to functional brain areas. Laser speckle imaging (LSI) is a noninvasive macroscopic technique with high spatial and temporal resolution used to monitor changes in capillary perfusion. In this study, the authors hypothesized that LSI can be useful as a noncontact method of functional brain mapping during awake craniotomy for tumor removal. Such a modality would be an advance in this type of neurosurgery since current practice involves the application of invasive intraoperative single-point electrocortical (electrode) stimulation and measurements. METHODS: After opening the dura mater, patients were woken up, and LSI was set up to image the exposed brain area. Patients were instructed to follow a rest-activation-rest protocol in which activation consisted of the hand-clenching motor task. Subsequently, exposed brain areas were mapped for functional motor areas by using standard electrocortical stimulation (ECS). Changes in the LSI signal were analyzed offline and compared with the results of ECS. RESULTS: In functional motor areas of the hand mapped with ECS, cortical blood flow measured using LSI significantly increased from 2052 +/- 818 AU to 2471 +/- 675 AU during hand clenching, whereas capillary blood flow did not change in the control regions (areas mapped using ECS with no functional activity). CONCLUSIONS: The main finding of this study was that changes in laser speckle perfusion as a measure of cortical microvascular blood flow when performing a motor task with the hand relate well to the ECS map. The authors have shown the feasibility of using LSI for direct visualization of cortical microcirculatory blood flow changes during neurosurgery.

Peripheral tissues, such as skin and muscles, are sensitive to alterations in perfusion. During circulatory shock, these tissues are the first to receive less blood and the last to recover after treatment. By monitoring peripheral circulation, disturbance of the systemic circulation can be detected at an early stage. Peripheral perfusion is often disturbed in critically ill patients. Peripheral perfusion may remain disturbed, even if conventional hemodynamic parameters such as blood pressure and heart frequency normalize after treatment. Persistent abnormal peripheral perfusion is related to a poorer clinical course. With current non-invasive methods, peripheral circulation in critically ill patients can easily be assessed at the bedside. Interventions that improve peripheral circulation may speed up recovery in critically ill patients.

Background. Setting the optimal level of positive end-expiratory pressure (PEEP) in critically ill patients remains a matter of debate. "Best" PEEP is regarded as minimal lung collapse and overdistention to prevent lung injury. In this study, global and regional variables were evaluated in a porcine model to identify which variables should be used to visualize "best" PEEP. Methods. Eight pigs (28-31 kg) were studied during an incremental and decremental PEEP trial before and after the induction of acute lung injury (All) with oleic acid. Arterial oxygenation, compliance, lung volume, dead space, esophageal pressure and electrical impedance tomography (EIT) were recorded at the end of each PEEP step. Results. After All, "best" PEEP was comparable at 15 cmH(2)O between regional compliance of the dorsal lung region by EIT and the global indicators: dynamic compliance, arterial oxygenation, alveolar dead space and venous admixture. After All, the intratidal gas distribution was able to detect regional overdistention at 15 cmH(2)O PEEP. "Best" PEEP based on transpulmonary pressure was lower and no optimal level could be found based on lung volume measurements alone. In addition, the recruitment phase significantly improved end-expiratory lung volume, PaO2, venous admixture and regional and global compliance, both in All and the "healthy" lung. Conclusion. Most of the evaluated parameters indicate comparable 'best' PEEP levels. However, a combination of these parameters, and especially EIT-derived intratidal gas distribution, might provide additional information. The application of lung recruitment was beneficial in both All and the "healthy" lung.

BACKGROUND:The aim of this paper was to study long-term survival in patients treated in the Intensive Care Unit (ICU) and who survived to hospital discharge. METHODS:This was a single-center retrospective cohort study of patients admitted to a mixed intensivist-led 10 bed ICU in a teaching hospital between 2004 and 2009 and discharged alive from the hospital with complete follow-up until January 1, 2011. RESULTS:A total of 3477 individual patients were admitted to the ICU, 491 (14.1%) of whom died in the hospital while 2986 survived to hospital discharge. In the first year after discharge 436 out of 2986 (14.6%) patients died. Mortality after hospital discharge was highest in the first three months. For patients discharged alive from the hospital the risk of dying during the first year increased significantly with age, APACHE II score at admission and being discharged to a place other than home. Sepsis on ICU admission, mechanical ventilation, renal replacement therapy during ICU treatment or admission type had no effect on one-year mortality rate. CONCLUSION/CONCLUSIONS:Patients who survive ICU treatment have a high risk of dying during the next year. This risk is almost as great the risk of dying during ICU and hospital treatment and increases with age and illness severity on admission to the ICU.

Circulatory shock is common and associated with high morbidity and mortality. Appropriate shock treatment relies on a good understanding of the pathophysiological mechanisms underlying shock. In this article, we provide an update on the description, classification, and management of shock states built on foundations laid by Dr Max Harry Weil, a key early contributor to this field.

PURPOSE: As brain death is a difficult concept for the lay public to understand, we hypothesized that allowing relatives of the patient to be present during brain death determination would improve their understanding of this condition and would eventually lead to an increased consent rate for organ donation. METHODS: A prospective multicenter trial was conducted in five Dutch hospitals. Relatives were given the opportunity to be present during brain death testing. The family consent rate for organ donation was the primary endpoint examined, and the degree of the relatives' understanding of brain death was the secondary endpoint. RESULTS: Between April 2010 and July 2011, we included the relatives of 8 patients in this study. The relatives witnessed brain death testing during this time. This sample size was too small to draw valid statistical conclusions. However, we have documented some noteworthy experiences of the relatives. CONCLUSIONS: Although, the hypothesis behind this study had promise, we were unable to reach our predefined goal. The possible causes for this shortcoming included the rarity of patients with brain death, the common practice in the Netherlands of obtaining consent for organ donation before brain death testing and the uneasiness of the staff in the presence of the patients' relatives during brain death determination. Although, we cannot draw a conclusion from statistical evidence, we would recommend that relatives be given the opportunity to be present during brain death testing and, specifically, during the apnea test.

OBJECTIVE: To evaluate sublingual microcirculatory and peripheral tissue perfusion parameters in relation to systemic hemodynamics during and after therapeutic hypothermia following out-of-hospital cardiac arrest. DESIGN: Prospective observational study. SETTING: Intensive cardiac care unit at a university teaching hospital. SUBJECTS: We followed 80 patients, of whom 25 were included after out-of-hospital cardiac arrest. INTERVENTION: In all patients, we induced therapeutic hypothermia to 33 degrees C during the first 24 hrs of admission. MEASUREMENTS AND MAIN RESULTS: Complete hemodynamic measurements were obtained directly on intensive cardiac care unit admission (baseline), during induced hypothermia (T1), directly after rewarming (T2), and another 24 hrs later (T3). In addition, the sublingual microcirculation was observed using sidestream dark-field imaging, and peripheral tissue perfusion was monitored with the peripheral perfusion index, capillary refill time, tissue oxygen saturation, and forearm-to-fingertip skin temperature gradient. During hypothermia, all sublingual microcirculatory parameters decreased significantly together with peripheral capillary refill time and the peripheral perfusion index, followed by a significant increase at T2. Changes in sublingual and peripheral tissue perfusion parameters were significantly related to changes in central body temperature, but not to changes in systemic hemodynamic variables such as cardiac index or mean arterial pressure. Surprisingly, these parameters were significantly lower in nonsurvivors (n=6) at admission and after rewarming. Persistent alterations in these parameters were related with the prevalence of organ dysfunction and were highly predictive of mortality. CONCLUSIONS: Following out-of-hospital cardiac arrest, the early postresuscitation phase is characterized by abnormalities in sublingual microcirculation and peripheral tissue perfusion, which are caused by vasoconstriction due to induced systemic hypothermia and not by impaired systemic blood flow. Persistence of these alterations is associated with organ failure and death, independent of systemic hemodynamics.