Does point of care prothrombin time measurement reduce the transfusion of fresh frozen plasma in patients undergoing major surgery? The POC-OP randomized-controlled trial

BACKGROUND: Bleeding is a frequent complication during surgery. The intraoperative administration of blood products, including packed red blood cells, platelets and fresh frozen plasma (FFP), is often live saving. Complications of blood transfusions contribute considerably to perioperative costs and blood product resources are limited. Consequently, strategies to optimize the decision to transfuse are needed. Bleeding during surgery is a dynamic process and may result in major blood loss and coagulopathy due to dilution and consumption. The indication for transfusion should be based on reliable coagulation studies. While hemoglobin levels and platelet counts are available within 15 minutes, standard coagulation studies require one hour. Therefore, the decision to administer FFP has to be made in the absence of any data. Point of care testing of prothrombin time ensures that one major parameter of coagulation is available in the operation theatre within minutes. It is fast, easy to perform, inexpensive and may enable physicians to rationally determine the need for FFP. METHODS/DESIGN: The objective of the POC-OP trial is to determine the effectiveness of point of care prothrombin time testing to reduce the administration of FFP. It is a patient and assessor blind, single center randomized controlled parallel group trial in 220 patients aged between 18 and 90 years undergoing major surgery (any type, except cardiac surgery and liver transplantation) with an estimated blood loss during surgery exceeding 20% of the calculated total blood volume or a requirement of FFP according to the judgment of the physicians in charge. Patients are randomized to usual care plus point of care prothrombin time testing or usual care alone without point of care testing. The primary outcome is the relative risk to receive any FFP perioperatively. The inclusion of 110 patients per group will yield more than 80% power to detect a clinically relevant relative risk of 0.60 to receive FFP of the experimental as compared with the control group. DISCUSSION: Point of care prothrombin time testing in the operation theatre may reduce the administration of FFP considerably, which in turn may decrease costs and complications usually associated with the administration of blood products. TRIAL REGISTRATION: NCT00656396.

Rapid measurement of S-100B serum protein levels by Elecsys S100 immunoassay in patients undergoing carotid artery stenting or endarterectomy

OBJECTIVES:: This study was designed to apply the rapid Elecsys(R) S100 immunoassay for real-time measurement of S100 protein serum levels indicating acute brain damage in patients undergoing carotid artery stenting (CAS) or endarterectomy (CEA). DESIGN AND METHODS:: Data of 14 CAS patients were compared to those of 43 CEA and 14 control patients undergoing coronary angiography (CA). S100 serum levels were measured by the full-automatic Elecsys(R) S100 immunoassay and compared to those obtained by the well-established LIA-mat(R) S100 system. RESULTS:: In contrast to CAS and CA patients, median S100 serum levels of CEA patients significantly increased to 0.24 ng/mL before declamping, but subsequently returned to baseline. Three CEA patients with neurological deficits showed sustained elevated S100 levels 6 h after extubation. Absolute S100 values were not significantly different between the two methods. Bland-Altman plot analyses displayed a good agreement, mostly indicating slightly smaller values applying the Elecsys(R) S100 system. CONCLUSIONS:: The Elecsys(R) S100 system appears to be suitable for rapid real-time detection of neurological deficits in patients undergoing CAS and CEA. Persistent elevations of Elecsys(R) S100 levels during CEA were associated with prolonged neurological disorders, whereas transient increases seem to represent impaired blood-brain barrier integrity without neurological deficits.

Indirectly measuring evaluations of several attitude objects in relation to a neutral reference point

This article presents a new response time measure of evaluations, the Evaluative Movement Assessment (EMA). Two properties are verified for the first time in a response time measure: (a) mapping of multiple attitude objects to a single scale, and (b) centering that scale around a neutral point. Property (a) has implications when self-report and response time measures of attitudes have a low correlation. A study using EMA as an indirect measure revealed a low correlation with self-reported attitudes when the correlation reflected between-subjects differences in preferences for one attitude object to a second. Previously this result may have been interpreted as dissociation between two measures. However, when correlations from the same data reflected within-subject preference rank orders between multiple attitude objects, they were substantial (average r = .64). This result suggests that the presence of low correlations between self-report and response time measures in previous studies may be a reflection of methodological aspects of the response time measurement techniques. Property (b) has implications for exploring theoretical questions that require assessment of whether an evaluation is positive or negative (e.g., prejudice), because it allows such classifications in response time measurement to be made for the first time.

Accounting for baseline differences and measurement error in the analysis of change over time

If change over time is compared in several groups, it is important to take into account baseline values so that the comparison is carried out under the same preconditions. As the observed baseline measurements are distorted by measurement error, it may not be sufficient to include them as covariate. By fitting a longitudinal mixed-effects model to all data including the baseline observations and subsequently calculating the expected change conditional on the underlying baseline value, a solution to this problem has been provided recently so that groups with the same baseline characteristics can be compared. In this article, we present an extended approach where a broader set of models can be used. Specifically, it is possible to include any desired set of interactions between the time variable and the other covariates, and also, time-dependent covariates can be included. Additionally, we extend the method to adjust for baseline measurement error of other time-varying covariates. We apply the methodology to data from the Swiss HIV Cohort Study to address the question if a joint infection with HIV-1 and hepatitis C virus leads to a slower increase of CD4 lymphocyte counts over time after the start of antiretroviral therapy.

Reproducibility and day time bias correction of optoelectronic leg volumetry: a prospective cohort study

Background Leg edema is a common manifestation of various underlying pathologies. Reliable measurement tools are required to quantify edema and monitor therapeutic interventions. Aim of the present work was to investigate the reproducibility of optoelectronic leg volumetry over 3 weeks' time period and to eliminate daytime related within-individual variability. Methods Optoelectronic leg volumetry was performed in 63 hairdressers (mean age 45 ± 16 years, 85.7% female) in standing position twice within a minute for each leg and repeated after 3 weeks. Both lower leg (legBD) and whole limb (limbBF) volumetry were analysed. Reproducibility was expressed as analytical and within-individual coefficients of variance (CVA, CVW), and as intra-class correlation coefficients (ICC). Results A total of 492 leg volume measurements were analysed. Both legBD and limbBF volumetry were highly reproducible with CVA of 0.5% and 0.7%, respectively. Within-individual reproducibility of legBD and limbBF volumetry over a three weeks' period was high (CVW 1.3% for both; ICC 0.99 for both). At both visits, the second measurement revealed a significantly higher volume compared to the first measurement with a mean increase of 7.3 ml ± 14.1 (0.33% ± 0.58%) for legBD and 30.1 ml ± 48.5 ml (0.52% ± 0.79%) for limbBF volume. A significant linear correlation between absolute and relative leg volume differences and the difference of exact day time of measurement between the two study visits was found (P < .001). A therefore determined time-correction formula permitted further improvement of CVW. Conclusions Leg volume changes can be reliably assessed by optoelectronic leg volumetry at a single time point and over a 3 weeks' time period. However, volumetry results are biased by orthostatic and daytime-related volume changes. The bias for day-time related volume changes can be minimized by a time-correction formula.

Outer skull landmark-based coordinates for measurement of cerebral blood flow and intracranial pressure in rabbits

Despite the increased use of intracranial neuromonitoring during experimental subarachnoid hemorrhage (SAH), coordinates for probe placement in rabbits are lacking. This study evaluates the safety and reliability of using outer skull landmarks to identify locations for placement of cerebral blood flow (CBF) and intraparenchymal intracranial pressure (ICP) probes. Experimental SAH was performed in 17 rabbits using an extracranial-intracranial shunt model. ICP probes were placed in the frontal lobe and compared to measurements recorded from the olfactory bulb. CBF probes were placed in various locations in the frontal cortex anterior to the coronary suture. Insertion depth, relation to the ventricular system, and ideal placement location were determined by post-mortem examination. ICP recordings at the time of SAH from the frontal lobe did not differ significantly from those obtained from the right olfactory bulb. Ideal coordinates for intraparenchymal CBF probes in the left and right frontal lobe were found to be located 4.6±0.9 and 4.5±1.2 anterior to the bregma, 4.7±0.7mm and 4.7±0.5mm parasagittal, and at depths of 4±0.5mm and 3.9±0.5mm, respectively. The results demonstrate that the presented coordinates based on skull landmarks allow reliable placement of intraparenchymal ICP and CBF probes in rabbit brains without the use of a stereotactic frame.

Effective compression ratio-A new measurement of the quality of thorax compression during CPR

PURPOSE: Computer-based feedback systems for assessing the quality of cardiopulmonary resuscitation (CPR) are widely used these days. Recordings usually involve compression and ventilation dependent variables. Thorax compression depth, sufficient decompression and correct hand position are displayed but interpreted independently of one another. We aimed to generate a parameter, which represents all the combined relevant parameters of compression to provide a rapid assessment of the quality of chest compression-the effective compression ratio (ECR). METHODS: The following parameters were used to determine the ECR: compression depth, correct hand position, correct decompression and the proportion of time used for chest compressions compared to the total time spent on CPR. Based on the ERC guidelines, we calculated that guideline compliant CPR (30:2) has a minimum ECR of 0.79. To calculate the ECR, we expanded the previously described software solution. In order to demonstrate the usefulness of the new ECR-parameter, we first performed a PubMed search for studies that included correct compression and no-flow time, after which we calculated the new parameter, the ECR. RESULTS: The PubMed search revealed 9 trials. Calculated ECR values ranged between 0.03 (for basic life support [BLS] study, two helpers, no feedback) and 0.67 (BLS with feedback from the 6th minute). CONCLUSION: ECR enables rapid, meaningful assessment of CPR and simplifies the comparability of studies as well as the individual performance of trainees. The structure of the software solution allows it to be easily adapted to any manikin, CPR feedback devices and different resuscitation guidelines (e.g. ILCOR, ERC).

Statistical evaluation of time-dependent metabolite concentrations: estimation of post-mortem intervals based on in situ 1H-MRS of the brain

Knowledge of the time interval from death (post-mortem interval, PMI) has an enormous legal, criminological and psychological impact. Aiming to find an objective method for the determination of PMIs in forensic medicine, 1H-MR spectroscopy (1H-MRS) was used in a sheep head model to follow changes in brain metabolite concentrations after death. Following the characterization of newly observed metabolites (Ith et al., Magn. Reson. Med. 2002; 5: 915-920), the full set of acquired spectra was analyzed statistically to provide a quantitative estimation of PMIs with their respective confidence limits. In a first step, analytical mathematical functions are proposed to describe the time courses of 10 metabolites in the decomposing brain up to 3 weeks post-mortem. Subsequently, the inverted functions are used to predict PMIs based on the measured metabolite concentrations. Individual PMIs calculated from five different metabolites are then pooled, being weighted by their inverse variances. The predicted PMIs from all individual examinations in the sheep model are compared with known true times. In addition, four human cases with forensically estimated PMIs are compared with predictions based on single in situ MRS measurements. Interpretation of the individual sheep examinations gave a good correlation up to 250 h post-mortem, demonstrating that the predicted PMIs are consistent with the data used to generate the model. Comparison of the estimated PMIs with the forensically determined PMIs in the four human cases shows an adequate correlation. Current PMI estimations based on forensic methods typically suffer from uncertainties in the order of days to weeks without mathematically defined confidence information. In turn, a single 1H-MRS measurement of brain tissue in situ results in PMIs with defined and favorable confidence intervals in the range of hours, thus offering a quantitative and objective method for the determination of PMIs.

Day-to-night time differences in the relationship between cardiorespiratory coordination and heart rate variability

Heart rate variability (HRV) and cardiorespiratory coordination, i.e. the temporal interplay between oscillations of heartbeat and respiration, reflect information related to the cardiovascular and autonomic nervous system. The purpose of this study was to investigate the relationship between spectral measures of HRV and measures of cardiorespiratory coordination. In 127 subjects from a normal population a 24 h Holter ECG was recorded. Average heart rate (HR) and the following HRV parameters were calculated: very low (VLF), low (LF) and high frequency (HF) oscillations and LF/HF. Cardiorespiratory coordination was quantified using average respiratory rate (RespR), the ratio of heart rate and respiratory rate (HRR), the phase coordination ratio (PCR) and the extent of cardiorespiratory coordination (PP). Pearson's correlation coefficient r was used to quantify the relationship between each pair of the variables across all subjects. HR and HRR correlated strongest during daytime (r = 0.89). LF/HF and PP showed a negative correlation to a reasonable degree (r = -0.69). During nighttime sleep these correlations decreased whereas the correlation between HRR and RespR (r = -0.47) as well as between HRR and PCR (r = 0.73) increased substantially. In conclusion, HRR and PCR deliver considerably different information compared to HRV measures whereas PP is partially linked reciprocally to LF/HF.

Measurement of nitric oxide and brain tissue oxygen tension in patients after severe subarachnoid hemorrhage

OBJECTIVE: Nitric oxide (NO), one of the most powerful endogenous vasodilators, is thought to play a major role in the development of delayed vasospasm in patients with subarachnoid hemorrhage (SAH). However, the role of the production of cerebral NO in patients with SAH is not known. In other SAH studies, NO metabolites such as nitrite and nitrate have been demonstrated to be decreased in cerebrospinal fluid and in plasma. METHODS: In this study, a microdialysis probe was used, along with a multiparameter sensor, to measure NO metabolites, brain tissue oxygen tension, brain tissue carbon dioxide tension, and pH in the cortex of patients with severe SAH who were at risk for developing secondary brain damage and vasospasm. NO metabolites, glucose, and lactate were analyzed in the dialysates to determine the time course of NO metabolite changes and to test the interrelationship between the analytes and clinical variables. RESULTS: Brain tissue oxygen tension was strongly correlated to dialysate nitrate and nitrite (r2 = 0.326; P < 0.001); however, no correlation was noted between brain tissue oxygen tension and NO metabolites in cerebrospinal fluid (r2 = 0.018; P = 0.734). No significant correlation between NO production, brain tissue carbon dioxide tension, and dialysate glucose and lactate was observed. CONCLUSION: Cerebral ischemia and compromised substrate delivery are often responsible for high morbidity rates and poor outcomes after SAH. The relationship between brain tissue oxygen and cerebral NO metabolites that we demonstrate suggests that substrate delivery and NO are linked in the pathophysiology of vasospasm after SAH.

Non-invasive measurement of steroids in fish-holding water: important considerations when applying the procedure to behaviour studies

Fish behaviourists are increasingly turning to non-invasive measurement of steroid hormones in holding water, as opposed to blood plasma. When some of us met at a workshop in Faro, Portugal, in September, 2007, we realised that there were still many issues concerning the application of this procedure that needed resolution, including: Why do we measure release rates rather than just concentrations of steroids in the water? How does one interpret steroid release rates when dealing with fish of different sizes? What are the merits of measuring conjugated as well as free steroids in water? In the ‘static’ sampling procedure, where fish are placed in a separate container for a short period of time, does this affect steroid release—and, if so, how can it be minimised? After exposing a fish to a behavioural stimulus, when is the optimal time to sample? What is the minimum amount of validation when applying the procedure to a new species? The purpose of this review is to attempt to answer these questions and, in doing so, to emphasize that application of the non-invasive procedure requires more planning and validation than conventional plasma sampling. However, we consider that the rewards justify the extra effort.