After publication of this article , it came to light that an earlier version had been published in error. This erratum contains the correct version of the article, which incorporates revisions made in response to reviewer comments. Additionally, one of the authors was inadvertently omitted from the author list. This author, Justin Yan, has been included in the corrected author list above.2 (PtCO2) is a continuous and non-invasive measure recommended by scientific societies in the management of respiratory distress. The objective of this study was to evaluate the correlation between PtCO2 and arterial partial pressure of CO2 (PaCO2) by arterial blood gas analysis in emergency patients with dyspnoea, and to determine the factors that interfere with this correlation.Transcutaneous CO2 was attached to the ear lobe of the patient before the gas analysis. Anamnesis, clinical and laboratory parameters were identified.From January to June 2014, all adult patients admitted to the RR with dyspnoea during business hours were included in the study if arterial blood gas measurements were indicated. A sensor measuring the PtCO2 and PaCO2 was R2 =.83 (p<.001) but became lower for values of PaCO2 above 60 mm Hg. The mean bias (± SD) between the two methods of measurement  was −1.4 mm Hg (± 7.7) with limits of agreement from −16.4 to 13.7 mm Hg. In univariate analysis, PaO2 interfered with this correlation. After multivariate analysis, temperature  and PaO2  significantly interfered with this correlation.Ninety patients with dyspnoea were included (104 pairs of measurements). The median (IQR) age was 79 years (69 – 85). The correlation between PtCO2 and PtCO2 values for patients admitted to the emergency department for acute respiratory failure. One limiting factor to routine use of PtCO2 measurements in the emergency department is the presence of hyperthermia.There is a significant correlation between PaCO However, for non-ventilated patients, assessment of EtCO2 is more complex, less accurate, and often impossible. For these patients, the recently recommended [2) could represent an alternative for immediate and continuous assessment of pCO2. Numerous studies of both children [2 and PtCO2. Yet in the specific setting of the emergency department (ED) resuscitation room (RR), PtCO2 has been poorly studied. The main objective of this study was to investigate the relationship between measures of PtCO2 and PaCO2 for patients admitted to the ED RR. The secondary objective was to determine the variables that may disrupt the link between PtCO2 and PaCO2.This is a corrected version of the previously published article . Arterian (SaO2) . Similarommended , 7 transchildren , 9 and achildren –12 have We conducted this single-center prospective observational study from January to June 2014 in the ED of Nîmes University Hospital, France. This study was reviewed and approved by our Institutional Review Board (number: 13/06–02) and was declared to and approved by the national commission for data processing and civil liberties. All patients provided written informed consent. This study is in compliance with the Helsinki Declaration.All adult patients admitted to the RR with dyspnoea during business hours  were included in the study if arterial blood gas measurements were indicated. In our ED, patients are admitted to the RR if they are level 1 or level 2 according to the Canadian Triage and Acuity Scale (CTAS). Thus, patients with dyspnoea are admitted to the RR if they suffered from severe respiratory distress, asthma, or important dyspnoea. Definition of CTAS level 1 and level 2 for dyspnoea are specified in Appendix 1. Exclusion criteria were incorrect installation of the sensor, signal abnormality on the monitor, and backup error on the memory of the device.2 measurement was performed by a Stow-Severinghaus sensor . The sensor heats skin to a temperature of 44 °C resulting in a dilatation of the capillary bed that allows for diffusion of gases (CO2 and O2) [+ and HCO2 value through the Henderson-Hasselbalch formula [2 TOSCA monitor  before the study commenced. For included patients, the PtCO2 sensor was attached to the ear lobe of the patient allowing for continuous measurement of PtCO2. After stabilization of the monitor to obtain a good signal, arterial blood gases and PtCO2 measurements were performed simultaneously. The medical team was blinded to the value of PtCO2 measured.The PtCO and O2) . On the  formula . Medical2 and PtCO2 values. The sample size calculation was based on the anticipated variation in the differences between the measurements and the required precision. Using a previous study [2 values were automatically saved every ten seconds by the monitor. Medical patient data were collected and entered into an electronic database after initial collection on paper case report forms (CRF). Blood pressure, heart rate, respiratory rate, blood oxygen saturation, Glasgow coma scale, temperature, time to completion of arterial blood gases, catecholamine use, and non-invasive ventilation or tracheal intubation were recorded by the attending physician. Characteristics of patients such as ED arrival modalities, hospital length of stay, and biological data were collected on the CRF.The primary outcome was concordance between the simultaneous PaCOus study  for an e2 and PaCO2 was evaluated by linear regression (correlation coefficients) and Bland-Altman analysis, which determined bias, precision, and agreement of PtCO2 and PaCO2, taking the automated analysis in the laboratory as the reference standard. The Pearson correlation coefficient was used to demonstrate the presence or absence of a relationship between PtCO2 and PaCO2. Relationships between measurement differences (|PaCO2- PtCO2 |) and patient characteristics were investigated by regression analysis. Variables related to the difference between PtCO2 and PaCO2 in the univariate analysis  were further analyzed in a multivariate model . We included PaCO2 in this model but did not included pH or PtCO2 to avoid a collinear bias. Overall model fit was assessed using the Hosmer-Lemeshow test. All statistical tests were two sided. A p-value less than.05 was considered significant for all analyses.Patient characteristics were described using qualitative (frequencies and percentages) or quantitative variables (means and standard deviations or median with interquartile ranges - depending on type of distribution) where appropriate. The concordance between PtCOAnalyses were performed with the use of R 3.0.2 . The authors had full access to and take full responsibility for the integrity of the data.2 values   +10.86. The Bland-Altman analysis is shown in Fig. p<.001). For the group with PaC02 < 60 mm Hg, R2 =.70 (p<.001) and the mean bias was −3.5 mm Hg (± 5.0). For the group with PaC02 > 60 mm Hg, R2 =.57 (p<.001) and the mean bias was 4.1 mm Hg (± 10.2).Between January 2014 and June 2014, 102 patients were screened for eligibility. Ninety patients were included and analyzed with 104 PtCO2 and PtCO2 was PaO2 , we found the temperature and the PaO2 to be significantly associated with a large difference between PaCO2 and PtCO2  and the limits of agreement (bias ± 1.96 SD) between the two techniques were −16.4 mm Hg and 13.7 mm Hg. There was a significant correlation between PaCO2 and PtCO2 . Because most of our patients were non-intubated, our results highlight the feasibility and the potential benefit of measuring PtCO2 since EtCO2 cannot easily be monitored in non-intubated patients. The correlation coefficient in our study was comparable to what was shown in a previous intensive care study  [2 coefficient, ranged between.91 and.99 [2 values were reported as possibly interfering with the correlation between PtCO2 and PaCO2 [2 may differ from one physician to another. Because some operators used the monitor less frequently, this may have led to poorer reproducibility. However, it also reflects our center’s daily practice and this issue may occur with any change of device. Thirdly, we did not correct the arterial blood gases according to the patient’s temperature and this may explain a portion of the increased difference. Finally, our population was more likely to have significant dyspnoea and therefore agitation or diaphoresis leading to movement of the sensor may have led to inaccurate measurements. Indeed, in the Gancel et al. study [To our knowledge, our study is the largest cohort of PtCO; p<.01) . However1 and.99 ). We assnd PaCO2 , 19–21. nd PaCO2 , patientl. study  where th2 values were generally greater than PaCO2 values. Indeed, our linear regression equation is PaCO2 = (0.81 × PtCO2) + 10.86. This overestimation is in accordance with available literature [2 and PtCO2 values [2 values above 60 mm Hg. The value of the mean bias reported in our study corresponds to those found in the literature (−1.4 to 4.6 mm Hg) [2 values has been previously reported. The accuracy of PtCO2 seems to be better for patients with PaCO2 values below 56 mm Hg [2 and PtCO2 . The issue that the temperature can influence the correlation has been raised by Rodriguez et al. [2 and PtCO2 values. This poor correlation can be explained by the fact that asthe patient’s temperature increased, the difference between the patient and the temperature sensor (44 °C) decreased, resulting in small changes in local perfusion and production of CO2. This hypothesis follows directly from the operating principle of the sensor [2 and PtCO2 [Our study found that PtCOterature , 23 and 6 mm Hg) , 24, 25.56 mm Hg . One exp56 mm Hg . In our z et al. . Our linnd PtCO2 . Unfortund PtCO2  cannot n2 and PtCO2 in patients with shock who are treated with catecholamines [2 and PtCO2. Several studies have shown that the correlation is not affected by catecholamines but by dermal vasoconstriction secondary to a state of shock [Although several studies have found a poor correlation between PaCOolamines , we did of shock , 27.2 diffusion to the skin and therefore on the PaCO2 values [Secondly, body mass index (BMI) was not measured in our study. Several studies reported conflicting conclusions regarding the influence of skin thickness, indirectly estimated by BMI, on the CO2 values , 25, 26.2 values .2 and PaCO2 values. This analysis would be important to predict PaCO2 values from continuous measurement of PtCO2, especially for patients requiring several hours of monitoring [Finally, one subject that remains to be explored is the intra-individual correlation. Most of the patients had only one arterial blood gas measurement during their management in the RR, which was inadequate for obtaining intra-individual correlations between different PtCOnitoring , 30.2 and PtCO2 values for patients admitted to the ED for acute respiratory failure. This correlation is particularly accurate for values below 60 mm Hg. One limiting factor to routine use of PtCO2 measurements in the ED is the presence of hyperthermia.There is a significant correlation between PaCO2 and PtCO2 values for patients admitted to the emergency department for acute respiratory failure.There is a significant correlation between PaCOThis correlation is comparable to that which has been shown in intensive care.2 measurements in the ED is the presence of hyperthermia.One limiting factor to the use of PtCOSevere respiratory distress: serious intracranial events, pneumothorax, near death asthma , chronic obstructive pulmonary disease exacerbations, cardiac heart failure, anaphylaxis and severe metabolic disturbances .Asthma: severe asthma defined with a combination of objectives measures and clinical factors which relate to the severity of symptoms, vital signs and history of previous severe episodes. If the forced expiratory volume in 1 second or peak expiratory flow rate are below 40 % predicted or previous best, the patient is considered severe.Dyspnea: this is subjective and may correlate poorly with lung function or deficits in oxygen uptake and delivery. Depending on the age, previous history and physical assessment one may not be able to distinguish between asthma chronic obstructive pulmonary disease, cardiac heart failure, pulmonary embolism, pneumothorax, pneumonia, croup, epiglottitis, anaphylaxis or a combination of problems.


Kidney injury molecule-1 (KIM-1), a recently discovered transmembrane protein, is expressed in dedifferentiated proximal renal tubular epithelial cells in damaged regions. Kidney injury early detection in diabetic patients has great importance for therapy and prognosis. Therefore, the aim of the present study is to predict, validate and evaluate the presence of KIM-1 in kidney inflammation, dialectic and diabetic nephropathy diseases.Sixty males and females subjects (30-52 years) were selected for this study. They were subdivided into three main groups; kidney injury, diabetic and diabetic nephropathy patients. The work was extended to evaluate KIM-1 after treatment of each disease.p < 0.0001) with the disease severity.The results revealed significant elevation of KIM-1 in the diseased groups and a noticeable reduction after treatment. Diabetic nephropathy recorded the highest KIM-1 level than the AKI state or the diabetic patients. We noticed an association between KIM-1 and sex and a positive correlation (In conclusion, urinary KIM-1 has been reported to be a noninvasive, rapid, sensitive, and reproducible biomarker to detect early kidney injury. We speculate that KIM-1 is expected to be a therapeutic target for kidney injury. Renal epithelial cell injury is the feature of many acute and chronic renal diseases. Kidney injury molecule-1 (KIM-1), a recently discovered transmembrane tubular protein, is markedly induced in renal injury including acute kidney injury (AKI) and chronic kidney disease (CKD) . In renaA long duration of elevated blood glucose levels (i.e. poorly controlled diabetes) is considered the major underlying mechanism causing diabetic nephropathy and chronic kidney disease . InteresThe aim of the present study is to predict and evaluate the KIM-1 level in patients with kidney inflammation, early stage of diabetic nephropathy and diabetic patients with detectable kidney inflammation. In addition, the role of KIM-1 to be consider as a diagnostic tool after treatment of such disease.Participants were recruited from Kasr Al-Aini Clinics at Kasr Al-Aini university hospital, Cairo, Egypt. This research was performed on 60 males and 60 females aged 30-52 years. Each sex was classified into four main groups (15 subjects each). Group 1 served as healthy control. Group 2 was patients with kidney inflammation (KI). Subgroup 2 was the same patients of group 2 and undergoes the classical treatment of inflamed kidney. Group 3 was diabetic patients (insulin independent). Subgroup 3 was the same members of group 3 and treated for diabetes. Group 4 was patients with diabetic nephropathy. Subgroup 4 was diabetic nephropathy patients of group 4 and treated for diabetes and kidney inflammation.Serum and urine samples were collected from healthy subjects who attending to Kasr Al-Aini Clinics, Cairo, Egypt for regular checkup. Individuals were informed of the testing to be performed and only the specified testing was performed on the collected reference specimens.Analyses were conducted with the full respect for the individual’s right to confidentiality. Information regarding their age and gender was also collected to estimate the glomerular filtration rate (GFR), urine and serum creatinine as well as blood glucose level in all the studied groups.KIM-1 patients, diabetic and diabetic nephropathy patients were diagnosed according to the reference values, where diabetes was defined as fasting plasma glucose ≥7.0 mmol/l (≥126 mg/dl) , glomeruAKI patients were treated with 500 mg of Cpirofloxacin  twice daily for 7 days and Urosolvine sachets  three times daily. Diabetic patients treated with 1 g of Glucophage  tablets daily. Diabetic nephropathy patients treated with the three above drugs for 7 days before the biochemical determinations of KIM-1.Urine samples were allowed to sit at room temperature for 30 minutes to sediment, and the supernatant was aliquoted and stored at -80°C until analysis.Construction of KIM-1 sandwich ELISA : The wells of Nunc-Maxisorp EIA plates were coated by diluting the capture antibody (72 μg/mL) to a working concentration of 0.4 μg/mL in PBS with 100 μL in each well. The plate was sealed and incubated overnight at room temperature. Each well was aspirated and washed using an automated microplate washer (Bio-Tek) with 400 μL of Wash Buffer (0.05% Tween-20 in PBS), repeating the process two times for a total of three washes. The plates were blocked by adding 300 μL of reagent diluent  to each well and incubated at room temperature for 2 hours. After washing as in the previous step, 100 μL of standard recombinant human KIM-1 (0-2000 pg/mL), control, and urine sample was pipette to the designated well, covered with an adhesive strip, and placed on the orbital shaker at 400 rpm at room temperature for 2 hours. The plate was washed using the same wash protocol as before, and 100 μL of the biotinylated goat anti-human KIM-1 detection antibody diluted in reagent diluent to a working concentration of 400 ng/mL was added to each well. The plate was covered with a new adhesive strip, incubated at room temperature for 2 hours with continued shaking at 400 rpm. Washing step was repeated and 100 μL of streptavidin-HRP diluted to a working dilution was added to each well. The plate was protected from light, covered with a new adhesive strip, shaken at 400 rpm, and incubated at room temperature for 20 minutes. After washing, 100 μL substrate solution was added to all wells, protected from light, covered with an adhesive strip, shaken at 400 rpm, and incubated at room temperature for 7 minutes. The reaction was stopped by adding 50 μL of stop solution to all wells. The absorbance was measured using a plate reader (BioTek Elx800) at 450 nm with an absorbance correction at 540 nm. The urinary KIM-1 concentration was calculated based on the standard curve and expressed in absolute terms (pg/mL).p < 0.05. Pearson’s test was done to detect correlation value with each parameter.Results were expressed as mean ± SD of 15 subjects in each group. Results were evaluated by using one way analysis of variance test (ANOVA), Costat Software Computer Program with least significance difference (LSD) between groups at All procedures followed were in accordance with the ethical standards of the Medical Ethical Committee at National Research Centre, Cairo, Egypt and with the Helsinki Declaration of 1975, as revised in 2008.Informed consent was obtained from all patients for being included in this study.The ability of biomarkers to predict kidney inflammation has been studied intensely in several different clinical settings. For a sound interpretation of the reported results, it is important to realize that the studies present a mixture of ‘AKI diagnosis confirmation’ in patients with established AKI and ‘AKI early prediction’ in patients with developing AKI. AKI has been defined as a rapid decline in glomerular filtration rate that occurs over hours or days . For theRegarding to the diabetic patients in our results, we noticed a significant increase in KIM-1in both males and females, although these patients not recorded any sign of kidney inflammation. The KIM-1 in male diabetic patient was significantly increase by 608.95% Figure . In agrePatients undergo classical diabetic treatment recorded significant decrease in KIM-1 by 42.31% in male and insignificant decrease in female by 13.16% as compared with the diabetic persons. Therefore, KIM-1 was improved after treatment by 300.02% in male and 133.91% in female and correlate positively with the high glucose level (Tables Concerning with diabetic nephropathy patients, the present study revealed significant increase in KIM-1 in males and females by 1275.20 and 2486.30%, respectively as compared with the healthy group (Figures We noticed that the KIM-1 in diabetic nephropathy patients recorded the highest level than in kidney inflammation state alone. This is may be due to the severity state of kidney inflammation associated with the diabetic state. Diabetic patients only may not have a complication as kidney inflammation or it may not reached to the diagnosis level which give an additional support to use KIM-1 as a diagnostic tool.In the present study, treatment of diabetic nephropathy patients showed significant decrease in KIM-1 level by 9.45% and 30.90% in male and females, respectively as compared with the diabetic nephropathy groups Tables . TherefoIn conclusion, KIM-1 might be a specific predictor for early detection of kidney inflammation, in diabetic disease where no sign of kidney inflammation was persisted, and in diabetic nephropathy disease. KIM-1 is expected to be a therapeutic target for kidney injury. KIM-1 and its potential value need to be validated in large studies and across a broader scope of clinical settings. Due to the relatively limited number of cases in this study, further studies are needed for accurately determine the use of KIM-1 as a biomarker, as the small sample size makes it difficult to evaluate its validity.


A significant number of surgical patients are at risk of intra- or post-operative complications or both, which are associated with increased lengths of stay, costs, and mortality. Reducing these risks is important for the individual patient but also for health-care planners and managers. Insufficient tissue perfusion and cellular oxygenation due to hypovolemia, heart dysfunction or both is one of the leading causes of perioperative complications. Adequate perioperative management guided by effective and timely hemodynamic monitoring can help reduce the risk of complications and thus potentially improve outcomes. In this review, we describe the various available hemodynamic monitoring systems and how they can best be used to guide cardiovascular and fluid management in the perioperative period in high-risk surgical patients. An estimated 230 million surgical procedures are performed each year around the world , and a s2) and prevent fluid overload and its consequences [The risk of perioperative complications is related to various factors, including patient status and comorbidities, the type of surgery performed and its duration, the degree of urgency, the skills and experience of the operating and anesthetic teams, and the post-operative management. Insufficient tissue perfusion and cellular oxygenation due to hypovolemia, heart dysfunction or both is one of the leading causes of perioperative complications and poor outcomes -9. Thus,equences -12. TherClinical examination remains an important initial step in the hemodynamic assessment of high-risk surgical patients. However, individual vital signs often lack the specificity and sensitivity that are needed to guide hemodynamic management. For example, blood pressure is a variable influenced by both cardiac output (CO) and vascular tone; hence, blood pressure can remain within the normal range in the presence of low-flow states, including hypovolemia, as a result of increased peripheral vascular resistance. Similarly, heart rate may fail to reflect the development of hypovolemia under anesthesia .2) can help differentiate between vasodilation and low CO as a cause of hypotension (PetCO2 transiently decreases when CO decreases) and may prevent ‘reflex’ fluid administration whenever blood pressure decreases. Similarly, a reduction in the PetCO2 value for the same minute ventilation (in the absence of hypothermia) suggests decreased pulmonary blood flow (and thus CO) and may serve as a trigger for more advanced hemodynamic monitoring.Combining and integrating parameters from various hemodynamic monitoring systems may help improve our understanding of hemodynamic status . For exaContinuous invasive measurement of arterial pressure helps identify the rapid fluctuations in arterial pressure that may occur in high-risk patients. Artifacts (over- or under-damping) should be carefully identified and eliminated, especially when systolic-diastolic components and waveform have to be analyzed. Non-invasive techniques for continuous measurement of blood pressure are usually performed in peripheral arteries and may become unreliable in case of vasoconstriction or low peripheral flow. Non-invasive assessment of pressure waveforms from more central measurement sites, such as the brachial artery, may be a valuable option in the future.A central venous catheter (CVC) is often used for administration of fluids, vasopressors, and inotropes and for measurement of central venous pressure (CVP). Since transmural CVP is the only value related to right ventricular (RV) preload but is not commonly monitored, interpretation of CVP values must take into account intrathoracic pressure changes, which are largely influenced by mechanical ventilation. Thus, changes in CVP with concomitant CO variations give an indication of RV function and potential peripheral venous congestion, the latter of which is an important factor for organ perfusion . In addi2). The main goal in this period is to maintain an adequate DO2 to meet the fluctuating tissue oxygen requirements. Global DO2 is determined by CO and the oxygen content of arterial blood, and so after correction of hypoxemia and anemia , maintenance of an adequate CO is the next logical step to improve DO2. There are various methods available for monitoring CO [The perioperative period is characterized by large variations in whole body oxygen consumption  or transesophageal (TEE) echocardiography can provide immediate point-of-care assessment of acute hemodynamic changes in selected patients. Echo techniques can also help to visualize the lungs, but this is beyond the scope of this review. Obviously, it is not possible to use TEE in all types of surgery. In addition to the estimation of CO , Doppler echocardiographic examination can provide an indication of cardiac function because it allows visualization of the cardiac chambers, valves, and pericardium . It alsoThe LV short-axis view, which can be used to evaluate LV function. Calculation of the LV fractional area contraction, or the simpler ‘eyeballing method’, informs about the kinetic (contractile) state and the shape (volume) of the heart. Poor contractility may indicate that inotropic support could help, and ‘kissing’ of the papillary muscle may indicate the need for fluids if the right heart is functioning normally. The short-axis view may also be used to identify septal dyskinesia. The finding of an RV D-shape may suggest the presence of RV dysfunction/failure, indicating a non-adaptation to an acute increase in RV afterload (pulmonary embolism) or RV myocardial ischemia.The four-chamber view, which can help in assessing LV and RV function by evaluation of the right-to-left size ratio .TEE provides several views, including the following:In more advanced echocardiographic evaluation, fluid status and fluid responsiveness can also be assessed in mechanically ventilated patients by means of the superior vena cava collapsibility index  or inferior vena cava distensibility index . In addition, echocardiography allows the rapid and reliable estimation of SV. Finally, there are particular and specific conditions in which diagnosis and treatment are strictly related to the echocardiographic examination .A miniaturized, disposable monoplane TEE probe that can be left in place for up to 72 hours  was recently introduced and has the potential to provide ongoing qualitative cardiac assessment . We beli2). Although the PAC can now be largely replaced by less invasive hemodynamic monitoring techniques in many cases, in some complex clinical situations , the PAC still represents a valuable tool when used by physicians adequately trained to correctly interpret and apply the data provided [Though criticized in recent years for its intrinsic invasiveness and no clear evidence of improved outcomes -25, the provided ,27. In sSV can be estimated continuously by analysis of the arterial pressure waveform, usually derived from an indwelling arterial catheter or by a non-invasive finger pressure cuff. To calculate SV from a pressure trace, the algorithms used by these devices have to compensate for the overall impedance of the system on the basis of the estimation of compliance and resistance of the cardiovascular tree. In this regard, optimization of the input signal is imperative, and severe distortions of the arterial waveform  and inadequate response of fluid-filled transducer systems   can resu2™ system  consists of a thermistor-tipped catheter which is usually placed in the femoral artery, although catheters for radial, axillary, or brachial applications are also available. The PiCCO™ device measures CO by transpulmonary thermodilution, which additionally provides the computation of volumetric preload parameters—global end-diastolic volume (GEDV) and intrathoracic blood volume—and extravascular lung water (EVLW). The CO measured by the Stewart-Hamilton principle from the thermodilution curve is used to calibrate a pulse contour algorithm, which measures the area under the systolic pulse pressure curve and calculates the SV in order to provide beat-by-beat CO measurement. The system has to be frequently recalibrated, at least every 8 hours in hemodynamically stable patients and more often if changes in vasoactive support are provided [The PiCCOplus™/PiCCOprovided . The sysprovided .The EV1000™/VolumeView™ system  has been more recently introduced and is analogous to the PiCCO™ monitor, using pulse wave analysis to calculate CO. A proprietary thermistor-tipped femoral artery catheter and a separate sensor are the main components of the system. This system requires calibration by transpulmonary thermodilution. It has been validated against the PiCCO™ and transpulmonary thermodilution in critically ill patients .plus system  uses pulse power analysis to calculate SV and therefore is not technically a pulse contour device. The algorithm is based on the principle of conservation of mass (power), assuming a linear relationship between the net power change and the net flow in the vascular system. This system requires correction for vascular compliance, with calibration using a transpulmonary lithium indicator dilution technique performed via an indwelling arterial catheter. It has been validated in critically ill patients [The LiDCO™patients ,33.The PulsioFlex™ system  displays trends of estimated CO by using the patient’s anthropometric and demographic characteristics , analysis of the arterial pressure tracing, and a proprietary algorithm for data analysis. The system requires a dedicated additional sensor, which can be connected to a regular arterial pressure catheter. Based on the same pulse contour algorithm used by the PiCCO™, the device can be calibrated by entering a CO obtained from an external source  or by the system’s own internal algorithm.rapid (LiDCO Ltd) device uses the same algorithm as the LiDCO™plus system, but instead of lithium dilution, nomograms based on the patient’s age, weight, and height are used to estimate SV and CO . An externally estimated CO can be used to calibrate the device.The LiDCO™The FloTrac™/Vigileo™ system (Edwards Lifesciences) consists of a proprietary transducer (FloTrac™) connected to a standard  arterial catheter. Individual demographic variables  and a database containing CO variables derived by using the PAC are used to calculate impedance and a ‘normal’ SV against which the standard deviation of the pulse pressure sampled during a 20-second interval is correlated to estimate CO. Arterial waveform analysis is used to calculate vascular resistance and compliance. The algorithm used by the Vigileo™ device has been modified over time, and recent studies evaluating the device in the perioperative setting have shown an improved performance and a significant reduction in the time needed to adapt to vascular dynamics. In the intensive care unit (ICU) setting, concerns remain regarding the accuracy in situations of acute hemodynamic instability as well as hyperdynamic conditions, although recent software modifications seem to improve the reliability of CO measurements. The FloTrac™/Vigileo™ system has been shown to be suitable for integration into perioperative optimization protocols, resulting in improved clinical outcomes ,35.With preloaded dataThe MostCare system , powered by the pressure recording analytical method, performs a beat-to-beat estimation of SV and CO by analyzing the pressure waveform, sampled at high resolution . The area under the pressure wave is determined during the whole cardiac cycle. In each phase, the method identifies specific points (‘points of instability’) characterized by modifications in velocity and acceleration in relationship to the previous and the subsequent point. All of these ‘points of instability’, mainly caused by reflected waves from the periphery (backward travelling waves), give the arterial pulse its specific profile, which is analyzed by MostCare for estimation of the vascular impedance (Zt). The contribution of the reflected waves to the forward travelling wave can be accurately identified only with a very high sampling rate. The ability to update the Zt during each heart beat makes the system extremely reactive when abrupt changes in impedance occur  ,37. AlthWithout preloaded dataRecently, several newly marketed monitors have purported to track changes in arterial pressure non-invasively from finger probes. These include the continuous non-invasive arterial pressure probe (used with the LiDCO™ system) and the ClearSight device (Edwards Lifesciences). Based on the volume-clamp technique of Penaz  incorporEsophageal Doppler offers a minimally invasive determination of CO. The CardioQ™/CardioQ-ODM™  is the most commonly used device. Esophageal probes measure blood flow in the descending part of the aorta. SV is calculated by multiplying the cross-sectional area of the aorta  by the blood flow velocity. Technical and methodological concerns regarding probe positioning and the use of nomograms have been raised.A transthoracic continuous Doppler CO monitor, the USCOM , is also available for intermittent SV and CO assessment. Using supra- or parasternal windows, flow velocity at the level of the aortic or pulmonary valves can be assessed non-invasively. Aortic diameter can be loaded from another measurement  or from a nomogram as mentioned above. The technique is rapid and can be used in adult and pediatric patients. Clinical validation studies have shown conflicting results, partially due to variations in signal acquisition inherent in the technique .2 rebreathing method, applies the Fick principle to CO2 in patients who are intubated and mechanically ventilated via a disposable rebreathing circuit that is added to the ventilator tubing. CO2 production is calculated as the product of CO2 concentration and airflow during a breathing cycle, and arterial CO2 content is derived from end-tidal CO2 and its corresponding dissociation curve. The rebreathing loop can induce an intermittent partial rebreathing state in 3-minute intervals. This rebreathing cycle results in an increased end-tidal CO2, mimicking a decrease in CO2 production. The differences in these values can be used to calculate CO. The system is not really clinically acceptable, because the assessment of CO is possible only in patients with fixed ventilator settings and good respiratory function with no relevant pulmonary shunt [The NICO™ System , using the partial COry shunt ,47.DDG-30® pulsed dye densitometry  is based on the transpulmonary dye dilution technique using indocyanine green (ICG). Signal detection in the arterial blood is performed by transcutaneous optical absorbance measurements similar to pulse oximetry. CO is calculated from the ICG-dye dilution curve according to the Stewart-Hamilton principle. Factors that compromise signal detection, such as vasoconstriction, interstitial edema, movement, or ambient light artifacts, all limit the reliability of CO assessment using this method .Electrical bioimpedance estimates CO continuously by detecting variations in thoracic or whole body impedance induced by cyclic changes in blood flow. Electrodes attached to the skin  or an endotracheal tube  provide electric current stimulation, and signal variations are analyzed by using mathematical algorithms. The reliability of these systems is poor ,50.The Bioreactance® technique  analyzes the variations in the frequency spectra associated with delivery of an oscillating electrical current. This technique may be somewhat superior to the bioimpedance technique ,52 but iAlthough CO can be measured with reasonable accuracy and precision with some of these systems, it is difficult to assess the optimal CO for an individual patient. A ‘normal’ or even high CO does not preclude the presence of inadequate regional and microcirculatory flow, and a low CO may be adequate in a context of low metabolic demand, especially during surgery under general anesthesia. Moreover, simple identification of a low CO does not tell us what to do about it. To correctly interpret the data acquired by any of the described devices, we need to combine/integrate several variables to help decide whether the CO/SV is adequate and how it can be optimized in the most effective manner.All monitoring systems have unique characteristics in terms of accuracy, precision, validity, stability, and reliability . Not allAre we ready to accept a less accurate measurement in order to limit invasiveness? Figure . A less Do we need continuous, semi-continuous, or intermittent measurements? Most complications after surgery do not have a sudden onset  or an obvious cause  but develop slowly; therefore, semi-continuous or intermittent measurements may be acceptable. However, it should be noted that only beat-by-beat measurement of SV allows assessment of the response to preload-modifying maneuvers, such as a fluid challenge or passive leg raising (PLR) test.Are calibrated or uncalibrated systems preferable? Non-calibrated systems are acceptable for the operating room (OR) or the post-anesthesia care unit (PACU) but may not be suitable for more complex cases, especially in the ICU. In unstable patients, there is a necessity to ‘re-calibrate’ more often because of frequent changes in vascular tone and also because derived variables  need to be re-calculated. A practical option may be to use an uncalibrated system in the OR/PACU and replace it with a calibrated system in the ICU.What alarms do we need? A major problem for patient surveillance by telemetric monitoring is artifact robustness. Any system with too many false alarms is prone to failure as personnel become desensitized.What kind of monitoring for what kind of patient? This is not a ‘one size fits all’ decision; rather, the optimal monitoring technique for each patient will vary depending on the degree of risk and the extent of the surgical procedure Figure .Several questions can be raised when considering choice of CO monitoring in the perioperative period:2 to injured tissues, which is associated with an increased incidence of post-operative complications. Moreover, the systemic inflammatory response associated with tissue injury results in capillary leak and tissue edema. Fluid restriction and diuresis may decrease edema in patients with poor ventricular function but may also increase the incidence of acute kidney injury. Meanwhile, excessive fluid administration may lead to a range of adverse effects, including coagulopathy and edema of lungs, gut, and peripheral tissues , changes in CVP over time may be helpful to guide fluid therapy, especially when the CVP is low and associated with low flow. A CVP of more than 8 mm Hg might also be considered an ‘alarm’ for potential venous congestion associated (or not) with fluid overload .plus, PiCCO2™, and EV1000™ monitors. EVLW can help in the identification of (cardiogenic or non-cardiogenic) pulmonary edema and has the potential to increase the safety of fluid therapy in patients with structural lung disease, acute respiratory distress syndrome, or congestive heart failure.GEDV and EVLW: These are volumetric parameters derived from transpulmonary thermodilution and are integrated into the PiCCO™The end-diastolic area of the left ventricle may be the most reliable static parameter of preload but is largely dependent on LV diastolic compliance. Its ability to accurately predict fluid responsiveness is limited.Positive pressure ventilation induces cyclical changes in intrathoracic pressure, which affect preload by decreasing venous return to the right heart and increasing venous return to the left ventricle. The degree of the resulting changes in LV SV  and pulse pressure  better predict fluid responsiveness than do static parameters, when RV function is not a limitation and for a fixed tidal volume. Most devices using pulse contour analysis, including the current version of the non-invasive ClearSight monitor, display SVV and PPV. Despite the numerous validity criteria required to interpret such variations, these variables may help predict fluid responsiveness at different thresholds and have been integrated into hemodynamic optimization protocols .Respiratory variations in the pulse oximeter plethysmographic waveform have been shown to predict fluid responsiveness in mechanically ventilated patients, similar to changes in the arterial pressure waveform . The MasIt is important to note that all of the dynamic variables have significant confounding factors . The relA PLR test has been suggested to overcome some of these limitations in dynamic evaluation but should be performed rigorously with simultaneous analysis of continuous CO monitoring. It is obviously impractical during most operative conditions . In addiDespite these limitations and confounding factors, whenever possible, one is advised to assess fluid responsiveness by using the available functional hemodynamic parameters before attempting to increase CO with fluid administration. This approach can indicate if and when CO can be further increased by fluids and can identify when the flat portion of the cardiac function curve has been reached, thus preventing unnecessary fluid loading . It is i2 may reflect important pathophysiological changes in the relationship between DO2 and VO2, both of which may fluctuate significantly during the perioperative period.Changes in SvOReorganization of the Fick equation shows that:2 will decrease in the presence of hypoxemia, hypermetabolic states (increased VO2), a decrease in CO, or anemia. Therefore, changes in SvO2 are directly proportional to those in CO but only when arterial oxygen saturation (SaO2), VO2, and Hb concentration remain constant. The SvO2 is around 75% in healthy patients but is closer to 70% in acutely ill patients who have a somewhat lower Hb concentration.where C is the amount of oxygen bound to 1 g of hemoglobin (Hb). From this equation, it is clear that SvO2) is used as a surrogate for SvO2 when a PAC is not in situ, but has some limitations. Although the determinants of ScvO2 and SvO2 are similar, they cannot be used interchangeably [2 and VO2 result in differences in the Hb saturation of blood in the superior and inferior vena cavae [2 is affected disproportionately by changes in the upper body and does not reflect the SvO2 of coronary sinus blood [2 may be slightly less than SvO2 [2 may exceed SvO2 by up to 20% [2 do not closely reflect those of SvO2 [Central venous oxygen saturation  was associated with a shorter hospital stay [Lower values of ScvO surgery . Therefotal stay . In patital stay .2 are uncommon [2 values imply first and foremost that CO may be inadequate. At the same time, very high ScvO2 values may imply that oxygen extraction is low, purporting a worse prognosis, at least during cardiac surgery [During surgery, this measurement is less informative: firstly, hypoxemia is generally corrected; secondly, under anesthesia, especially with neuromuscular paralysis, oxygen use decreases in all tissues, so that reductions in ScvOuncommon . Neverth surgery .Lactate is a physiological substrate (carbohydrate) produced from pyruvate reduction during cytosolic glycolysis. In stable conditions, lactate production and elimination are equivalent , leading to a stable blood lactate concentration of 0.8 to 1.2 mmol/L. The net flux of lactate depends on the difference between release and uptake and varies among organs and with their energetic conditions . HyperlaThere is good evidence that use of flow-based hemodynamic monitoring combined with hemodynamic manipulation in the perioperative period can reduce morbidity and sometimes mortality ,91-97. FOne option is reactive, by applying a rapid intervention only when a hemodynamic change occurs. One should then individualize treatment with fluid challenge techniques. The response to the rapid administration of a fluid bolus  can be evaluated during surgery . The response can be monitored by evaluating the blood pressure or heart rate, but the CO/SV response is much more accurate. Inotropic agents are added in the absence of an adequate response.2 values to minimize the risk of tissue hypoperfusion. Adequate fluid administration is the first element of this strategy. Several studies have indicated that fluid management based on PPV, SVV, and SV optimization may decrease post-operative wound infections and possibly post-operative organ dysfunction [The other option is pro-active and is based on a strategy of hemodynamic manipulation targeting supranormal CO or DOfunction ,100. Inofunction . The usefunction ,103.There are basically two options to optimize perioperative cardiovascular management Table , both ofper se in the perioperative setting has not been linked to improved outcomes; however, appropriate measurement and interpretation of cardiovascular variables may help guide therapeutic interventions, which in turn can improve patient outcomes. The most appropriate system must be selected for the individual patient prior to surgery, taking into consideration the individual risks of the patient and the procedure. Appropriate interpretation of the information offered by hemodynamic monitoring requires the integration of several variables. Echocardiography is increasingly used as a first tool to identify a problem and help select initial treatment. To improve patient management and outcome, the clinician must understand the advantages and the limitations of the various tools and parameters used during perioperative care.Cardiovascular monitoring systems play an important role in optimizing perioperative hemodynamic management. Use of hemodynamic monitoring devices


Aims. To assess the association of blood oxygen-transport capacity variables with the prevalence of diabetic retinopathy (DR), retinal ischemia, and macular oedema in patients with type 2 diabetes mellitus (T2DM). Methods. Cross-sectional, case-control study (N = 312) with T2DM: 153 individuals with DR and 159 individuals with no DR. Participants were classified according to the severity of DR and the presence of retinal ischemia or macular oedema. Hematological variables were collected by standardized methods. Three logistic models were adjusted to ascertain the association between hematologic variables with the severity of DR and the presence of retinal ischemia or macular oedema. Results. Individuals with severe DR showed significantly lower hemoglobin, hematocrit, and erythrocyte levels compared with those with mild disease and in individuals with retinal ischemia and macular oedema compared with those without these disorders. Hemoglobin was the only factor that showed a significant inverse association with the severity of DR  and retinal ischemia . Lower erythrocyte level showed a marginally significant association with macular oedema . Conclusions. In patients with DR, low blood oxygen-transport capacity was associated with more severe DR and the presence of retinal ischemia. Low hemoglobin levels may have a key role in the development and progression of DR.  Type 2 diabetes mellitus (DM) is a common disease with a prevalence and incidence that have increased in recent decades. The estimated increase in the total number of people with diabetes is from 366 million in 2011 to 552 million in 2030 , whereas, in men, the odds ratio of this association was not significant.The results of the multivariate models showed that lower levels of hemoglobin were associated with the severity of DR and the presence of retinal ischemia. In the case of macular edema, the association with the lower number of erythrocytes was significant. In addition, a significant interaction between the level of hemoglobin and sex, depending on the degree of diabetic retinopathy, was observed . The mulThe results of our study failed to demonstrate an independent association between the concentration of Hb and the presence of DR. However, we found that lower Hb is associated with severe forms of DR and with the presence, until now not described, of retinal ischemia. We also demonstrated for the first time an association between low levels of red blood cells and the presence of EMCS.Different factors have been described to be associated with the development and severity of DR in patients with type 2 DM –11. Thes.Anemia is suggested as another long-term complication of DM and, together with ischemia, has been associated with the development and progression of both microvascular and macrovascular complications. Ischemia is a critical component of DR, and it is potentially influenced by anemia, the main indicator of the blood oxygen delivery capacity . PreviouThere are several studies showing the role of anemia as an independent risk factor for diabetic retinopathy, particularly in population-based studies , 15, 26.Other studies in the literature consider anemia to be a predictor of DR , 14, 17.Anemia and low hematocrit have been found to also be associated with the presence of diabetic macular edema , 32. In There were several limitations in the present study that should be noted here because they may affect the generalization of our findings. Because this was a cross-sectional study, the results do not provide information on the potential causation effect of hemoglobin. Prospective and larger studies are required to overcome this limitation. Further, the results of this study should be interpreted with caution because it was not designed primarily to respond to these associations. The evaluation of the association between hematological parameters and the presence and severity of DR was a secondary objective. For this reason, though the majority of the patients included in the study were postmenopausal, this variable was not evaluated.One of the strengths of this study is its case-control design, which enabled us to assess whether there are differences between patients with and without DR. The specific exclusion of other complications associated with diabetes, such as nephropathy and cardiovascular disease, provides us with a study population that is free of microvascular and macrovascular disease, with the exception of the retinopathy. This eliminates the influence of these factors, especially renal insufficiency, as confounding variables and differentiates this study from the majority of the previously published studies.There is an association of low blood oxygen-transport capacity, measured by hemoglobin concentration, and an increased severity of DR and the presence of retinal ischemia. These findings might have clinical implications, such as those in attempt to better control hemoglobin concentrations in diabetic patients, particularly in those with advanced forms or DR ischemia. In patients with these conditions, it would be advisable to monitor and prevent anemia. Prospective studies specifically designed to test these associations are needed to confirm low values of hemoglobin as a risk factor for DR and retinal ischemia also in patients with type 1 DM. Clinical trials in patients with anemia are needed for the further confirmation of these associations.


IAs are detected in 2.3% of adults. Systemic hypertension is a risk factor. Screening for IA in certain high-risk groups, such as patients with coarctation of the aorta, has been discussed in international guidelines. Patients with coarctation often have concomitant systemic hypertension. Moreover, the prevalence of hypertension in patients with coarctation and IA is significantly higher than those without IA. It is uncertain whether hypertension alone represents a sufficient risk factor to prompt screening for IAs.t tests and categoric variables by Fisher exact test (p<0.05 = significant).Consecutive patients referred from our tertiary hypertension clinic underwent comprehensive magnetic resonance assessment including CMR and 3D time-of-flight MRA imaging at 1.5T. The study was conducted in accordance with The Governance Arrangements for Research Ethics Committees. Cerebral MRAs were double reported by a blinded Neuroradiologist. Demographic data, including presentation office systolic (SBP) and diastolic blood pressures (DBP), aneurysm data and CMR-derived left ventricular mass (LVM) indexed to body surface area, age and gender were recorded. Continuous variables were compared by Student -2 p=0.9375, number of antihypertensive medications: 3.0±2.0 vs 2.6±1.6 p=0.5015).One hundred and twenty one n=121) MRAs were included . IAs were detected in 10 patients (8.2%) (table 21 MRAs wThe prevalence of IA in this cohort is significantly higher than the general population. Subgroup analysis failed to identify particularly high-risk groups within the hypertension cohort studied. All aneurysms detected were small and managed conservatively, consequently the clinical benefit of routine screening for IAs at the time of CMR in hypertensive patients remains unanswered.NIHR Cardiovascular Biomedical Research Unit, Bristol Heart Institute.JCLR: Clinical Society of Bath Postgraduate Research Bursary.ECH: BHF grant IBSRF FS/11/1/28400.


Previous investigations to establish factors influencing the blood flow restriction (BFR) stimulus have determined cuff pressures required for complete arterial occlusion, which does not reflect the partial restriction prescribed for this training technique. This study aimed to establish characteristics that should be accounted for when prescribing cuff pressures required for partial BFR.Fifty participants were subjected to incremental blood flow restriction of the upper and lower limbs by proximal pneumatic cuff inflation. Popliteal and brachial artery diameter, blood velocity and blood flow was assessed with Doppler ultrasound. Height, body mass, limb circumference, muscle–bone cross-sectional area, adipose thickness (AT) and arterial blood pressure were measured and used in different models of hierarchical linear regression to predict the pressure at which 60 % BFR  occurred.r = 0.58) and AT (r = −0.45) were the largest independent determinants of lower and upper body partial occlusion pressures. However, greater variance was explained by upper and lower limb regression models composed of DBP and BMI (48 %), and arm AT and DBP (30 %), respectively.Combined analysis revealed a difference in cuff pressures required to elicit 60 % BFR in the popliteal (111 ± 12 mmHg) and brachial arteries (101 ± 12 mmHg). MAP (Limb circumference has limited impact on the cuff pressure required for partial blood flow restriction which is in contrast to its recognised relationship with complete arterial occlusion. The majority of the variance in partial occlusion pressure remains unexplained by the predictor variables assessed in the present study. Blood flow restricted (BFR) exercise is a training modality generating substantial research interest. Studies have demonstrated that this training stimulus can elicit similar hypertrophic and strength gains as traditional heavy load resistance exercise    on the level of BFR. It is likely the degree of intramuscular pressure depends on the architecture features of the muscle. Hypertrophied muscles have a greater thickness and volume, and subsequently blood flow occlusion may occur at relatively lower pressures  influencing the BFR stimulus have determined the external cuff pressure required for complete arterial occlusion (100 % BFR)  should be accounted for when prescribing the cuff pressure required for BFR. The latter was estimated by determining the relationship between cuff pressure and the level of blood flow restriction for each individual which was achieved by measuring the changes in conduit artery diameter, blood velocity and blood flow in response to proximal cuff inflation over a range of external pressures.Fifty participants  volunteered to take part in the investigation. All were fully informed of the purposes, risks and discomforts associated with the experiment before providing written consent. The study conformed to guidelines outlined in the Declaration of Helsinki and was approved by Loughborough University Ethics Advisory Committee.All tests were conducted 4 h post-prandial in a quiet, temperature-controlled room (24 ± 1 °C). Participants abstained from exercise, alcohol and tobacco for 24 h prior to the experimental test. Upon arrival into the laboratory, participant’s height and body mass were measured using a stadiometer and manual scales. Anthropometric assessments of the right thigh and arm were made, followed by B-mode ultrasound measures of anterior and posterior subcutaneous adipose tissue thickness. Participants then rested supine for 20 min prior to arterial blood pressure measurement and vascular assessments. Doppler ultrasound was used to image the popliteal and brachial artery in response to incremental blood flow restriction induced by proximal pneumatic cuff inflation.2. Thigh circumference was measured horizontal to the long axis of the femur at the mid-point between the inguinal fold and the anterior aspect of the patella. The horizontal  line was marked and extended to intercept with the vertical mid-line of the anterior and posterior surface of the thigh. Subcutaneous adipose tissue thickness overlying the quadriceps and hamstrings were measured at these sites. Arm circumference was measured horizontal to the long axis of the humerus at the mid-acroniale-radiale distance. The horizontal  line was marked and extended to intercept with the vertical mid-line of the anterior and posterior surface of the arm. Subcutaneous adipose tissue thickness overlying the biceps and triceps were measured at these sites.Height (m) and body mass (kg) were measured with a stadiometer and scales, respectively. Body mass index (BMI) was calculated as kg/mπ[(r − AT)2] where r is the radius of the limb calculated as circumference/2π and AT is ultrasound measured adipose thickness  line, on the anterior and posterior surface of the limb. Subcutaneous adipose tissue was imaged at depth of 2–5 cm, depending on the site and individual. Minimal force was applied through the transducer to avoid compression of the adipose layer. Two ultrasound B-mode images  were systematically acquired at each site  and later analysed using Image J software. On each image, subcutaneous fat thickness was measured between skin–fat and fat–muscle interfaces at four sites and the average of eight values recorded. Limb adipose thickness (AT) was determined by averaging values attained at anterior and posterior sites . Muscle–bone CSA was estimated using the formula Systolic (SBP) and diastolic (DBP) blood pressures were measured from the brachial artery, following 5-min supine rest, using an automated blood pressure cuff . Blood pressure was taken in triplicate and the closest two values averaged for analysis. Mean arterial pressure (MAP) was calculated as DBP + (SBP − DBP)/3 in accordance with Levick .Popliteal artery Participants lay in a prone position for 20 min before the test protocol commenced. A 13 cm wide pneumatic cuff  was positioned on the right thigh overlying marks used for the prior anthropometric assessment. Popliteal artery diameter and velocity were measured using duplex ultrasound behind the popliteal fossa at depths of 3–4 cm (11–9 MHz). All images of the popliteal artery were acquired proximal to the branching of the tibial artery; however, distance variation between participants was required to ensure the highest possible image quality. Baseline measures of the artery were recorded for 30 cardiac cycles before commencing the inflation protocol. The thigh cuff was initially inflated  to 90 mmHg for 150 s and then deflated for 180 s. Ultrasound images of the popliteal were recorded for the final 30 s of each inflation step (after 2 min of inflation) to ensure attainment of steady state flow  was positioned on the upper arm overlying marks of prior anthropometric assessment. Brachial artery diameter and velocity were measured using duplex ultrasound directly downstream of the cuff >3 cm proximal of the olecranon process. With the starting pressure of 60 mmHg the same inflation/deflation procedure for ultrasound image acquisition was used as described for the popliteal artery.Analysis of blood flow restriction Popliteal and brachial artery diameter and flow velocity during each pressure step were analysed with a custom-designed, edge detection and wall tracking software . Media-to-media diastolic diameter was measured within a specified region of interest on B-mode images. The Doppler flow velocity spectrum was traced and TAMV (cm/s) computed. Synchronised diameter and velocity data, sampled at 20 Hz, enabled calculation of blood flow and shear rate. Resting diastolic diameter (mm) was averaged over 30 cardiac cycles. Blood flow (ml/min) was calculated as (TAMV × πr2) × 60, where r is the radius of the artery lumen. Resting blood flow was averaged over 20 cardiac cycles. Shear rate was derived from Poiseuillies law and calculated accordingly as (4 × TAMV)/diameter. The day-to-day reproducibility of resting brachial artery measurements were; diameter (0.2 %), velocity (16 %) and blood flow (16 %). The day-to-day reproducibility of resting popliteal artery measurements were; diameter (0.5 %), velocity (16 %) and blood flow (17 %).t test determined differences in baseline conduit artery variables  between sexes. A two-way mixed measures ANOVA was used to evaluate the conduit artery response  to incremental pressures  in males and females. This was followed by one-way repeated-measures ANOVA to confirm change with incremental pressures in males and females separately. Bonferroni corrected post hoc t tests were then used to locate significance. Blood flow at each cuff pressure was expressed relative to baseline (without cuff) to quantify the level of restriction. Individual data were then fitted with a second order polynomial equation for the prediction of cuff pressure (mmHg) at 60 % BFR. Pearson’s correlation was then used to determine the relationship between dependent (cuff pressure at 60 % BFR) and predictor variables . This provided an order for entering variables into the hierarchical linear regression models. Different models of hierarchical linear regression were used to predict the pressure at which 60 % BFR occurred in both the popliteal and brachial artery. Models consisted of 2–3 blocks. Pearson correlation, SEE and the change in the F value was assessed as each individual variable was added to the overall model. Only a single variable for blood pressure , anthropometry  and limb specific morphology  was entered in each model to avoid multi-colinearity. There was no concern regarding multi-colinearity among predictor variables in the hierarchical linear regression models [variance inflation factor (VIF) <2.7].Data was analysed using SPSS statistical package (IBM SPSS Statistics 20). A Shapiro–Wilk test was used to confirm normal distribution and a Mauchley test of sphericity to verify homogeneity of variance. An independent n = 47; 24 males, 23 females).Ultrasound images were of insufficient quality in three participants preventing quantification of blood flow restriction, and were therefore excluded from the results. Whole group subject characteristics are presented in Table P < 0.001) popliteal (4.61 ± 0.41 vs. 5.72 ± 0.60 mm) and brachial (3.29 ± 0.48 vs. 4.10 ± 0.52 mm) arteries than males. Popliteal and brachial artery diameters  with external pressures of 130 and 110 mmHg . The artery diameter response to incremental pressure differed between the sexes in the brachial but not the popliteal artery . Contrasts revealed that the diameter of the brachial artery decreased at a lower pressure in the females (110 mmHg) compared to the males (120 mmHg) (P = 0.023).Female participants had smaller P < 0.00 poplitea−1, P < 0.001) and brachial  arteries compared to females. Blood velocity . The blood velocity response to incremental pressure .Male participants demonstrated higher baseline blood velocity in the popliteal (17.6 ± 3.5 vs. 13.7 ± 2.6 cm sP < 0.001) in the popliteal (272 ± 67 vs. 136 ± 37 ml min−1) and brachial (154 ± 61 vs. 73 ± 25 ml min−1) arteries in females compared to males. Blood flow . This response differed between the sexes . Contrasts revealed that males experienced a larger decrease in popliteal and brachial blood flow with initial cuff inflation at 90 mmHg (P = 0.004) and 60 mmHg (P = 0.008), respectively.Baseline blood flow was lower (P = 0.0002). Partial BFR (60 %) was achieved in the popliteal artery at different cuff pressures for males (114 ± 15 mmHg) and females (105 ± 10 mmHg) (P = 0.03). In contrast, there was no difference in the pressure required to elicit 60 % BFR in the brachial artery between males (102 ± 18 mmHg) and females (100 ± 14 mmHg) (P = 0.67). No relationship was observed between thigh and arm cuff pressures (r = 0.02). Correlations between subject variables and the external cuff pressure required for 60 % BFR are presented in Table Individual participant blood flow restriction data was fitted with a second order polynomial equation for the prediction of cuff pressure at 60 % BFR Fig. . Combiner = 0.58, Table r2 = 45 %) in the cuff pressure required for 60 % BFR, but adding thigh circumference (block 3 of model 1) did not  in the cuff pressure required for 60 % BFR. The addition of thigh circumference did not explain any additional variance (Sig F change = 0.936). Standardised betas and part correlation coefficients indicated that DBP explained most variance from each individual block. A reduced SEE indicates an increased accuracy of prediction with model 2 compared to model 1 . To exclude potential error associated with BMI in certain populations (athletes), a third model  in the cuff pressure required for 60 % BFR. Although MAP was an independent predicting variable  and DBP (72 mmHg) were entered into the regression equation generated from model 1 Table . The preThis study has demonstrated between-subject variation in the level of blood flow restriction at different external cuff pressures applied to upper and lower limbs. With wide cuff (13 cm) application the external pressure required to illicit 60 % BFR in the popliteal was 111 ± 12 mmHg and was greater than in the brachial at 101 ± 12 mmHg. MAP and AT were the largest independent determinants of lower and upper body partial occlusion (60 % BFR) pressures, respectively. Despite entering further variables into an upper (DBP and BMI) and lower (DBP and AT) limb regression model, the majority of variance remains unexplained.Efficacy in BFR exercise is achieved by balancing the level of blood flow restriction, with an appropriate level of muscle activation and fatigue (contractile/metabolic impairment), so as to ensure an appropriate training load   and brachial (r = 0.27) arteries suggests restrictive cuff pressures should not be based on SBP alone. The restriction of brachial artery blood flow at low–moderate external cuff pressures (60–100 mmHg) was less than anticipated. Previous investigations have shown increased electromyographic activity during elbow flexion exercise at cuff pressures as low as 50 mmHg  compared to males (114 ± 15 mmHg). However, there was no difference in the pressure at 60 % BFR in the brachial artery between sexes (100 ± 14 mmHg vs. 102 ± 18 mmHg). This difference in responses between the popliteal and brachial artery is unlikely to be due to a disparity in limb size, since circumference of the arm and thigh are proportionately larger in males versus females. An alternative is that findings reflect differences between sexes in local vascular function. For example, Nishiyama et al.  noted thStepwise regression models were used to determine what subject characteristics should be accounted for when prescribing the restriction cuff pressure for lower and upper limb BFR training. Although MAP had the strongest independent relationship with pressure at 60 % BFR in the popliteal artery, more variance (48 %) was explained by entering DBP alongside BMI in the regression model. Accounting for thigh circumference and DBP, in accordance with Loenneke et al. , resulteIt was found that SBP, though often used to determine the restrictive cuff pressure during BFR exercise, did not explain additional variance in either lower or upper body regression models. This is in agreement with others who report a weak correlation between SBP and arterial occlusion pressure in normotensive adults  and even absent  relationship between limb circumference and partial occlusion pressure in the popliteal and brachial arteries was observed. This was unexpected since the percentage of external cuff pressure reflected in the underlying tissue, and therefore vasculature, is inversely related to the circumference of the limb . Constriction of the artery in response to low-flow is mediated by endothelin-1  and thigh circumference (no greater than 66.7 cm) therefore these results may not be generalizable to obese individuals (or those with limb circumferences outside the range in this study). Participants were resting in a supine position during blood flow measures, while BFR protocols involve exercise and are typically performed in the seated or standing position. A similar relationship between cuff pressure and blood flow would be expected during exercise; however, the cuff pressure required to result in a given level of blood flow restriction would likely be elevated due to the activated skeletal muscle pump and increased BP in response to postural changes and the pressor response of exercise.We acknowledge the limitations of the present study. The sample size is relatively small compared to other similar studies  on the external pressure (using a 13 cm wide cuff) required to elicit 60 % reduction in popliteal and brachial artery blood flow. MAP and AT were the largest independent determinants of lower and upper body partial occlusion pressures but greater variance was explained by regression models composed of DBP and BMI (48 %), and arm AT and DBP (30 %), respectively. In contrast, limb circumference has limited impact on the cuff pressure required for partial blood flow restriction. However, this may be due to the narrow range in limb circumference observed in healthy subject populations as investigated here. Nevertheless, the majority of the variance in partial occlusion pressure remains unexplained by the predictor variables assessed in the present study. Further investigation of the influence of local vessel characteristics is required if studies are to achieve an equal BFR between subjects. Sex sensitivities in the regulation of arterial vascular tone may also need to be considered.


To examine the effects of intravenous sedation and oral nifedipine on blood pressure and pulse rate in patients with perioperative high blood pressure undergoing implant surgery, the clinical records of dental implant patients managed by intravenous sedation at our outpatient dental offices were retrospectively evaluated.A total of 516 clinical charts were evaluated. The subjects were divided into two groups: a normotensive group with no history of hypertension and a hypertensive group with a history of hypertension. The patients in the hypertensive group were further divided into two subgroups: with or without nifedipine administration before operation. Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate (PR), and rate pressure product (RPP) were assessed.In 30 patients (33%) of the hypertensive group, the high blood pressure on arrival obviously declined to around or less than 160 mmHg; in the remaining patients in the group who showed a mean SBP of 182.1 ± 13.8 mmHg on arrival, the blood pressure did not decrease after a 30-min rest. Oral nifedipine administered to the patients with sustained high blood pressure decreased SBP to 144.7 ± 23.1 mmHg in 28.1 ± 9.3 min after administration, comparable to that in hypertensive patients without nifedipine.For patients with stage 2 hypertension before operation, it may be difficult to maintain the recommended blood pressure during surgery by only intravenous sedation; reduction of blood pressure by antihypertensive drugs may be necessary. Osseointegrated dental implants were introduced in Japan in 1983, and the procedures are now performed very frequently. Dental implants are placed in a wide age range of patients, including elderly patients with hypertension. Patients with very high blood pressure are at great risk for acute medical problems when undergoing stressful dental procedures, such as oral surgery, periodontal surgery, and placement of dental implants [Patients with normal blood pressure <120/80 mmHg), prehypertension (120 to 139/80 to 89 mmHg), or stage I hypertension (140 to 159/90 to 99 mmHg) may receive regular dental care, but those with stage 2 hypertension (≥160/≥100 mmHg) should receive noninvasive treatment only and be referred to the physician for immediate follow-up [0/80 mmHgPain, stress, or anxiety-related dental procedures can raise blood pressure in both hypertensive and normotensive patients . We haveA retrospective review of the clinical records was conducted for 336 patients who received dental implant-related surgeries combined with intravenous sedation between January 2008 and February 2012 at our outpatient dental offices. Among the patients, 125 patients received multiple surgeries during the observation period: 4 patients underwent surgery five times, 7 patients four times, 29 patients three times, 85 patients twice, and others once. The following surgical procedures were performed in a total of 516 patients: dental implant placement (466 patients), sinus lift surgery and dental implant (28 patients), socket lift and dental implant (10 patients), and guided bone regeneration and dental implant (12 patients).We performed surgeries after medical consultation when patients had a history of hypertension or cardiovascular or cerebrovascular diseases. History of ischemic heart disease, renal dysfunction, diabetes mellitus, cerebral infarction, or articular rheumatism was documented in 17 patients in the hypertensive group and 16 patients in the normotensive group. They were confirmed stable and well controlled for implant surgery. For patients who received therapeutic drugs, surgery was performed following daily medication.The patients were allowed to have water or snacks until 2 h before the visit. On arrival at the office, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate (PR) were measured using an automatic blood pressure monitor with an oscillometric method . The cephalic vein was cannulated with a 22-G disposable intravenous catheter. Nifedipine capsule (10 mg) was orally administered to patients with sustained increases in SBP ≥160 mmHg for 30 min from baseline measurement. A noninvasive blood pressure monitoring system with electrocardiogram (ECG) monitor and pulse oximeter  was mounted, and blood pressure was measured at 2- to 5-min intervals. In patients with a history of cardiovascular disease, ECG was continuously monitored. Following confirmation of a definite decline of blood pressure or SBP <160 mmHg, infiltration anesthesia and/or conduction anesthesia was administered using 1 to 3 cartridges (1.8 to 5.4 ml) of 2% lidocaine containing 1/80,000 epinephrine.Following confirmation of a sufficient anesthetic effect, intravenous sedation with continuous infusion of propofol 1 to 2 mg/kg/h and midazolam 20 to 40 μg/kg bolus together with inhalation of oxygen 3 L/min via nasal cannula was initiated. After confirming Verrill sign, implant surgery was initiated. During operation, the propofol dose was adjusted to maintain the optimum conscious sedative condition  , and locThe subjects were divided into two groups: a normotensive group with no history of hypertension and a hypertensive group with a history of hypertension. Thirteen patients who had no history of hypertension were included in the hypertensive group, since they indicated SBP ≥160 mmHg on arrival at the office and were later diagnosed with essential hypertension by cardiologists. Furthermore, the patients in the hypertensive group were divided into two subgroups: with or without nifedipine administration.2) were sampled at the point of arrival to the office, prior to the initiation of sedation, 30 min after the initiation of operation, and on completion of operation. Furthermore, rate pressure product (RPP: SBP × PR) was calculated.From the clinical chart, data of SBP, DBP, PR, and percutaneous oxygen saturation (SpOThere were two primary outcome measures: (1) incidence of improved hypertension following oral nifedipine and (2) incidence of normal ranges of hemodynamic parameters during surgery. The secondary outcome variable was incidence of hypertension related to perioperative complications.In this study, we used data from all cases (516 cases) for statistical analysis.t test was used to compare demographic variables between groups. Fisher's exact test was used to compare ratios of patients in hypertensive group between subgroups. One-way analysis of variance (ANOVA) followed by Tukey's multiple comparison test was performed to examine the change in the values of parameters. Repeated measures ANOVA followed by Dunnett's multiple comparison test was used to compare the values of parameters in groups at each time point. Statistical analysis was performed using Prism 5 for Windows Ver. 5.01 . The significance level was set at p < 0.05.Data were described as mean ± standard deviation. The unpaired This study protocol was approved by the ethics committee of Japanese Dental Society of Anesthesiology (No. 2015–4).p < 0.0001) and duration of surgery (p = 0.025) between normotensive and hypertensive groups. On arrival at the office, values of all hemodynamic parameters, including SBP, DBP, PR, and RPP, were higher in the hypertensive group than in the normotensive group (p < 0.0001).Patient demographics and clinical characteristics are summarized in Table Tables Although the mean SBP in the hypertensive group was significantly higher than that in the normotensive group during operation, SBP <160 mmHg was maintained in all patients except three in the hypertensive group (2.8%) and one in the normotensive group (0.2%). The values of DBP in patients in the hypertensive group were higher than those in the normotensive group throughout the observation course, and changes in DBP in each group were similar to those in SBP.On arrival at the office, RPP ≥12,000 bpm × mmHg was found in 74 patients (70%) in the hypertensive group and 111 patients (27%) in the normotensive group. More than 90% of the patients with preoperative nifedipine showed high RPP on arrival at the office. Among patients with high RPP, all patients in the normotensive group, 10% of the patients without nifedipine in the hypertensive group and 35% of patients with nifedipine in the hypertensive group had RPP <12,000 bpm × mmHg until initiation of intravenous sedation. The values of RPP during operation under intravenous sedation were maintained at a normal range except in nine patients (8.5%) in the hypertensive group and one patient (0.2%) in the normotensive group.p = 0.224) and then significantly decreased until completion of the operation (p < 0.001).In patients with oral nifedipine in the hypertensive group, the PR value slightly increased prior to initiation of intravenous sedation  of the 516 implant surgery cases, oral nifedipine had to be administered, since preoperative SBP was higher than 160 mmHg in these patients. Within 30 min of administration of nifedipine, SBP of hypertensive patients decreased to a similar range as that of hypertensive patients who did not need administration of oral nifedipine. Intravenous sedation after nifedipine administration to hypertensive patients resulted in stable hemodynamics during implant surgery.The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure  classifiIncreases in SBP due to psychological stress are proportional to age and baseline blood pressure . IntraveFor patients with stage 2 hypertension before operation, it is difficult to maintain the recommended blood pressure during surgery using only intravenous sedation, and it is necessary to decrease blood pressure by antihypertensive drugs. In this study, the blood pressure of patients with sustained hypertension was reduced to stage I hypertension about 30 min after administration of oral nifedipine. On the other hand, the decrease in RPP after oral nifedipine administration was not less than 12,000 bpm × mmHg, which could be due to the fact that an increase in pulse rate with nifedipine by reflex tachycardia. Thereafter, blood pressure and RPP during surgery under intravenous sedation has remained at levels similar to those of hypertensive patients with well-controlled blood pressure. Maximum effect (21.4% decreases in SBP) appears in 30 to 60 min and lasts about 3 h on oral administration of nifedipine . Since oThe overdose of vasoconstrictor that is added to the local anesthetic in order to prolong the anesthetic effect and hemostatic action may cause increased blood pressure and arrhythmias. Elevation of blood pressure in hypertensive patients is greater than that in normotensive patients during dental surgery . AlthougImplant surgery is performed in patients with a wide age range, including elderly patients with hypertension. Dentists or oral surgeons often encounter hypertensive patients who are undiagnosed or noncompliant. Among Japanese over the age of 30, 60% of men and 44.6% of women suffer from high blood pressure, and 33.8% of men and 25.6% of women with a history of hypertension have not been managed medically . In thisFor dental implant surgery in hypertensive patients who are not adequately controlled, the application of intravenous sedation and preoperative antihypertensive medication would be useful in order to prevent perioperative hypertension crisis including hypertension emergency with end-organ damage or hypertension urgency without end-organ damage. Since sublingual administration of immediate-release (IR) nifedipine may cause side effects such as significant decrease in blood pressure, reflex tachycardia, and acute myocardial infarction , the subIn this study, we showed that the stable hemodynamic was obtained by performing intravenous sedation and oral administration of nifedipine for patients with hypertension. It is important not only to understand the systemic management of the patient but also to obtain stabled hemodynamic by performing intravenous sedation and oral administration of nifedipine for patients with hypertension in order to perform the implant surgery safely, and it could be possible to prevent the medical sequelae.


Bidirectional inter-organ interactions are essential for normal functioning of the human body; however, they may also promote adverse conditions in remote organs. This review provides a narrative summary of the epidemiology, physiopathological mechanisms and clinical management of patients with combined renal and cardiac disease . Findings are also discussed within the context of basic research in animal models with similar comorbidities.Pertinent published articles were identified by literature search of PubMed, MEDLINE and Google Scholar. Additional data from studies in the author’s laboratory were also consulted.The prevalence of renocardiac syndrome throughout the world is increasing in part due to an aging population and to other risk factors including hypertension, diabetes and dyslipidemia. Pathogenesis of this disorder involves multiple bidirectional interactions between the kidneys and heart; however, participation of other organs cannot be excluded. Our own work supports the hypothesis that the uremic milieu, caused by kidney dysfunction, produces major alterations in vasoregulatory control particularly at the level of the microvasculature that results in impaired oxygen delivery and blood perfusion.Recent clinical literature is replete with articles discussing the necessity to clearly define or characterize what constitutes cardiorenal syndrome in order to improve clinical management of affected patients. Patients are treated after onset of symptoms with limited available information regarding etiology. While understanding of mechanisms involved in pathogenesis of inter-organ crosstalk remains a challenging objective, basic research data remains limited partly because of the lack of animal models.Preservation of microvascular integrity may be the most critical factor to limit progression of multi-organ disorders including renocardiac syndrome. More fundamental studies are needed to help elucidate physiopathological mechanisms and for development of treatments to improve clinical outcomes. Co-existence of kidney and cardiac disorders is increasingly prevalent throughout the world. A major consequence of failing kidneys is the stimulation of metabolic and humoral pathways that cause injury to remote organs; a similar scenario occurs with disorders of other organs such as the heart and liver. Mechanisms responsible for disease progression, regardless of the organ initially affected, are complex; understanding the mechanisms and pathways involved in, or responsible for inter-organ crosstalk, is a growing area of research interest. Clinical management of cardiorenal syndrome patients is particularly complex due to the involvement of multiple organs and the difficulty in targeting specific symptoms.Herein, we review recent advances concerning physiopathology, therapeutic interventions and complications of renocardiac syndrome. Recent data, including our own, from animal models are discussed here; primary focus is on the impact of acute kidney injury on systemic hemodynamics, blood flow regulation and endothelial function. Novel therapies that target the microcirculation could benefit renocardiac syndrome patients and improve mortality.Evaluation of underlying causes and physiopathological mechanisms responsible for kidney related disorders represents a significant challenge. Kidney and heart disease often co-exist; the heart is highly dependent on regulation of salt and water content by the kidneys that directly depend on blood flow and pressure generated by the heart. Functional deterioration of either organ initiates a vicious spiral of events that leads to multi-organ failure. Although prevalence of renal dysfunction in patients with heart disease is well known , 2 it reHerein, we provide a narrative review of clinical and basic science literature on renocardiac syndrome (type 3 and type 4 CRS) with regard to epidemiology, pathogenesis and clinical interventions designed to improve outcomes. Clinical and basic science reports were searched using MEDLINE and PubMed with the keywords reno-cardiac syndrome, kidney disease, heart disease and combinations thereof.Type 3 CRS is usually triggered by an episode of acute kidney injury (AKI); nephrons are particularly sensitive to ischemia and blood borne toxins. AKI is often superimposed on chronic renal disease and could be a necessary precursor of end-stage renal disease. Elucidation of mechanisms remains difficult due to the complex interplay between chronic and acute kidney disease phenotypes . Acute wType 4 CRS, on the other hand, involves chronic abnormalities of renal function due in part to aging, diabetes, hypertension and dyslipidemia that progresses to multi-organ disease  possiblyIn the UK, The National Confidential Enquiry into Patient Outcome and Death (http://www.ncepod.org.uk) survey, published in 2009, discovered a systematic failure by hospital staff to recognize complications of AKI which ultimately resulted in poor clinical outcomes. The report also underscored the importance of preventing all-cause early transient malfunction of the kidneys due to irreversible structural damage. Even though almost 20 million American adults are known to be affected by some form of kidney disease  the propClinical evaluation of Type 4 CRS is more obvious; responsible for almost 50 % of deaths in all age groups of CKD patients , 25. IndStudies of the physiopathological evolution of kidney injury, either acute or chronic, in humans are rare possibly because of the common misconception that tubular regeneration occurs in patients after AKI –38. ThisCardio-renal interactions are generally explained using extracellular fluid volume homeostasis and blood pressure control criteria . ConsequProgressive kidney dysfunction associated with chronic kidney disease, without either pharmacologic or non-pharmacologic intervention, ultimately results in multiple organ failure. Acid–base and electrolyte imbalance, fluid overload, atrial distension, hematologic dysfunction and diminished capacity to eliminate drugs all contribute. Physiopathologic mechanisms responsible for communications between kidney injury and cardiac dysfunction remain to be established; however, reduced cardiac performance ultimately limits blood perfusion of all organs including the kidneys and thereby contributes to renal injury. AKI affects the heart either 1- directly or 2- by limiting remote organ function which then indirectly influences cardiac function  produces rapid and significant functional changes in the heart characterized by LV dilatation and alterations of various functional parameters including LV relaxation time, fractional shortening and end-systolic and end-diastolic fractional shortening. Cardiocyte apoptosis has been suggested to play a role in promoting these changes along with stimulation of inflammatory mediators. Ischemia initiates a cascade of inflammation that is crucial to organ repair and if unchecked, eventual deterioration of organ function. In rodent models of acute and chronic kidney disease, the role of inflammation is predominant as evidenced by greater secretion of pro-inflammatory cytokines and infiltration of inflammatory cell types , 48. TheMechanisms involved in type 4 CRS are multi-faceted and invariably shared by different organs because of vascular disease and endothelial dysfunction as well as the cumulative toxic influences of uremia. A plethora of risk factors in these patients contributes to progression of cardiac and kidney failure; unique risks are also associated with dialysis procedures particularly in patients with end-stage renal disease . A recenUsing a two-stage subtotal nephrectomy uremia model  we have been able to provide evidence for significant perfusion abnormalities across the ventricular wall in relation to severity of kidney dysfunction (assessed by serum creatinine) . In normContinued investigation to determine the physiopathological mechanisms involved in development of renal disease after AKI will require a multifaceted and bidirectional approach. Identification of risk factors involved in early kidney injury might be the most logical approach to prevent and delay adverse outcomes;  as statestatus quo; however, evidence of a mortality benefit in patients with AKI remains controversial [Chuasuwan and Kellum recently reviewed different treatment strategies specific to the kidneys and heart based on RIFLE and AKIN criteria  that estoversial –60. Indeoversial , 62. CliType 4 CRS patient management requires a multidisciplinary approach because of the bidirectional, multifaceted physiopathology of this syndrome; treatment strategies are mostly targeted to risk factors such as anemia, hypertension and malnutrition , 64. HowWhile there is no consensus for pharmacological management of Type 3 or 4 CRS patients, there is general agreement that more evidence-based clinical studies are necessary. Numerous inotropes and vasodilators including neurohormonal antagonists and diuretics have been evaluated on the basis of their ability to increase urine output and glomerular filtration and lower serum creatinine (see recent review by Kim ). ModestAngiotensin converting enzyme inhibitors could also improve clinical outcomes (CONSENSUS ) but it B receptors of the collecting ducts to increase sodium reabsorption and 3- acts on alpha-1A receptors of renal vasculature to promote vasoconstriction [Non-pharmacologic treatments currently under investigation in clinical and animal studies also include renal denervation and remote conditioning. Renal denervation has been studied over the past 25 years to counter the effects of elevated renal sympathetic activity which 1-stimulates beta-1 receptors in the juxtaglomerular apparatus to increase renin release, 2- acts on alpha-1triction .afferent nerves transmit sensory information to the central nervous system from chemo- and mechanoreceptors in the kidneys; activation of renal afferent nerves is sympathoinhibitory in normal animals. Renal efferent nerves mediate changes in kidney function via innervation of all essential renal structures ; [Renal aratus);  activatiaratus); . Findingaratus);  however Two clinical trials, Simplicity HTN-1 and HTN-Remote conditioning stratagems  are the subject of a number of ongoing clinical trials ; numerous animal investigations have reported significant protection of vulnerable organs against ischemic injury by remote conditioning –93. IschBi-directional communication between the heart and kidneys occurs through various pathways that, in healthy subjects, modulate cardiac output, vessel tone, volume status and excretion of metabolic waste compounds. It is increasingly apparent that pathological changes in one organ can instigate the release of a cascade of mediators that promote secondary dysfunction or injury in another distant organ. Further controlled clinical and more robust fundamental research is necessary to clarify existing contradictory findings and to improve understanding of mechanisms responsible for development of inter-organ pathologies.