Background and Objective: Postoperative nausea and vomiting (PONV) is the main concern for 40-70% of patients undergoing laparoscopic cholecystectomy. Our objective was to compare carbon dioxide gas at low pressure and standard pressure for the occurrence of PONV on patients undergoing laparoscopic cholecystectomy.Methods: This double- blind trial was conducted on 50 women patients aged between 18 to 60 years with acute cholecystectomy. The patients were divided into two groups: low pressure (LP)  and standard pressure (SP) . Nausea and vomiting in patients at hours 0-4, 4-8, 8-12, 12-24 after the surgery were recorded.Results: The frequency of PONV in the LP and SP groups did not demonstrate statistically significant different (P > 0.05). Nevertheless the frequency of shoulder pain after 4 hours at the LP group compared with SP group was significantly different (P < 0.023).Conclusions: The use of low pressure gas compared to standard pressure gas to create pneumoperitoneum could not reduce the PONV whereas the frequency of shoulder pain in LP group was reduced. Low pressure gas was associated with reduction of surgeon visibility and subsequently more prolonged surgery duration.  Carbon dioxide is considered the major product of cellular metabolism and eliminated by a well-organized mechanism.7 Monitor of end tidal CO2 concentration is obligatory during the laparoscopy. It is suggested to employ the lowest intra-abdominal pressure allowing satisfactory exposure of the operative field, rather than using a routine pressure.8Carbon dioxide (COThe objective of this study was to find out the frequency of PONV in laparoscopic cholecystectomy at low pressure (8mm/Hg) vs. standard pressure (15mm/Hg) pneumoperitoneum.Study design and population: This double-blind trial was performed in a hospital affiliated to pain research center in Jundishapur University located in Ahvaz, Southwest Iran, from Dec. 2012 to Sep. 2013. A total of 50 women patients aged between 18 to 60 years old with acute cholecystitis were enrolled into the study. Exclusion criteria was defined as the patients who had cholangitis, history of motion sickness, malignancy, smoking, pregnancy and the patients who had received anti-emetic agents during the past 24 hours. Ethics Committee of Ahvaz Jundishapur University of Medical Sciences approved the study. A consent Form was received from the patients prior to the study.Intervention and measurement: Fifty qualified patients were randomly allocated for elective laparoscopic cholecystectomy to receive either standard pressure gas (14-15 mmHg) (n=25) or low pressure gas (7-9 mmHg) (n=25). Randomization was performed based on Color Cards (Blue & Red Cards).The patients belonged to class 1-2 in American Society of Anesthesiologist (ASA). All the laparoscopic cholecystectomies which performed by the same surgeon, standard monitoring and anesthetic management were standardized. Anesthesia was induced with: Midazolam 0.05 mg/kg, Fentanyl 2 mcg/kg, Thiopental 5 mg/kg and Cisatracurium 0.1 mg/kg. Mechanical ventilation was adjusted to maintain end-tidal CO2 tension 35-40 mmHg throughout the surgery. After induction of anesthesia, a nasogastric tube was passed into the stomach for suction and then removed. The patients were monitored for blood pressure and heart rate during the surgical procedure. At the end of the laparoscopic operations, surgeon was asked to state the quality of surgical field visualization. Also, when the patients were awake, questioner (who did not know the pressure gas) evaluated the nausea, vomiting and shoulder pain. The method used for pain control after operation was the infusion of Apotel 1 gr at recovery and repeat it after 6 hours and also, NSAIDs suppositories / PRN.9 According to VAS, the number “zero” indicates that the patient does not feel any nausea and number “10” represents that the most severe level of nausea perception.  .Vomiting was estimated based on frequency of emetic episode per 24 hours.. The patients with persisted nausea for more than 20-30 min received Ondansetron 4 mg and were excluded the study. Also, shoulder pain in recovery room and 4 hours after the surgery were examined.The patients were monitored for emetic symptoms within the first postoperative 24 hours for five times. Nausea and vomiting in patients were recorded at hours 0-4, 4-8, 8-12, 12-24, and after the surgery. Assessment of nausea intensity is difficult because the nausea is subjective, so in order to increase the accuracy of nausea assessment we used the visual analogue scale (VAS).Statistical considerations: The power of this study was considered 80%. Statistical analysis was performed using SPSS 19. The results were shown as mean ± standard deviation (SD) and 95% confidence intervals (CIs) of differences were calculated. We used Fisher exact and Chi Square tests to compare the variables between two groups. P < 0·05 was considered significant. P> 0.023). Furthermore, 4 hours after the surgery, 3 and 9 patients in the LP and SP groups complained of shoulder pain, and the difference was significant (P> 0.005).  . The fre 0.005). 10,11 The risk of intraoperative injury during laparoscopic cholecystectomy is higher than open cholecystectomy.12 Laparoscopic surgery as a minimal invasive intervention requires pneumoperitoneum for adequate visualization and operative manipulation. Carbon dioxide is considered as the most frequent gas used for creating pneumoperitoneum because of high diffusibility and quick absorption and excretion.2 in laparoscopy evokes local and systemic effects.14 Insufflations of CO2 into the peritoneum may change the acid-base balance, cardiovascular and pulmonary physiology, and in high risk patients they may elevate the postsurgical complications.5Open surgery has been substituted with laparoscopic cholecystectomy in the cholecystolithiasis treatment and it is now the gold standard in the treatment of benign gallstone disease.2 CO2 insufflations during laparoscopic surgery, causes peritoneal tension and irritation, playing main role in PONV.15PONV is frequent among the patients undergoing laparoscopic cholecystectomy. It can be very stressful to the patients, occasionally more than the operation itself.4 Different mechanisms have been mentioned for PONV after laparoscopic surgery. One of them is the dilation of brain vessels by CO2 increasing intra cranial pressure (ICP) and consequently the possibility of nausea and vomiting.16 Clinical and laboratory studies have revealed that ICP elevation is not directly relevant to the hemodynamic changes caused by the increased intra-abdominal pressure. The possible mechanism of increased ICP associated with insufflation may be impaired venous drainage of the lumbar venous plexus following increased intra-abdominal pressure.17 PONV is affected by many factors which related to patients, surgery and anesthesia. These variable items requires 5-Hydroxytryptamin (5.HT) secretion in a cascade of events concluding both the central nervous system and Gastro-intestinal tract.18 In addition, serotonin may play a role in pathogenesis of PONV. Various other mechanisms have been proposed for PONV after laparoscopic, including the effect of CO2 on the occurrence of ischemia in visceral tissues.19 PONV is decreased with the administration of high concentration oxygen,20 fluid therapy,21 and sympathomimetic agents.22The first step in preventing of PONV after laparoscopic cholecystectomy is to decrease the patient risk factors, surgical intervention, anesthetic method, and postoperative cares.2O is administered as the unique anesthetic agent, it is recognized to cause of PONV. N2O can also be a reason of PONV because of change in middle ear pressure and bowel distension after diffusion in to closed cavities.23Likewise Propofol usage for anesthesia preservation has a positive effect on PONV reduction when NIn the present study, the use of low pressure gas instead of standard pressure gas could not significantly reduce the frequency of PONV after the surgery. Additionally, the duration of anesthesia, surgery and pneumoperitoneum were higher in the LP group; however, there were no significant differences. More prolonged duration of surgery was due to the reduction of visibility of the surgeon.et al. compared the low gas pressure with the standard gas pressure on PONV after laparoscopic gynecologic surgery. They reported that the use of low pressure CO2 was not effective in reducing the incidence and severity of PONV.5Kim et al. administration of 80% oxygen during surgery was able to reduce the incidence of nausea and vomiting in gynecologic surgery.24 Researchers have illustrated that using CO2 to create pneumoperitoneum reduce 54% in the blood stream of the organs when using of intra- abdominal gas pressure (IAP) 15 mmHg instead of IAP 10 mmHg.25In a study by Goll 26 In our study shoulder pain after the surgery was assessed. When leaving the recovery room 20% and 48% of the patients experienced the shoulder pain in LP and SP groups respectively. Also, after 4 hours of surgery, 12% and 36% of the patients respectively complained the shoulder pain in LP and SP groups. Esmat et al. indicated that reduction of (CO2) pressure and the use of normal saline into the peritoneal membrane could reduce the frequency, percentage of shoulder pain after surgery in different hours after the operation from 35.2% to 18.4%.27A broad spectrum of adverse effects results from uncontrolled postsurgical pain.The present study had some limitations. We did not measure parameters involved in nausea and vomiting, including the amount of blood supply of the organs and tissue oxygenation. To obtain the most appropriate gas pressure, we suggest the assessment of gas pressure with less or higher rate than the standard range.2 gas compared to standard pressure one to create pneumoperitoneum could not reduce nausea and vomiting after surgery. However, the frequency of shoulder pain in the low pressure gas group was reduced. Our findings demonstrated that during the operation, low pressure CO2 pneumoperitoneum was associated with problems including the reduction of surgeon visibility and subsequently more prolonged surgery duration. In this study, the use of low pressure CO


Cytotoxic chemotherapy is the standard treatment in most cancer patients with advanced stage. However, many patients suffer from severe side effects even if the anti-cancer treatment is effective. There is no established strategy to prevent wide range of side effects of cytotoxic chemotherapy including acute renal injury. Cisplatin is a highly effective chemotherapeutic agent used to treat various malignancies, but its utility is compromised by its nephrotoxicity. C-type natriuretic peptide (CNP), a member of the natriuretic peptide family, exhibits anti-inflammatory effects by activating its specific receptor, guanylyl cyclase (GC)-B. CNP and GC-B receptor are known to be expressed in both the vascular endothelium and kidney. However, there is no evidence about CNP protection against tissue injury by cisplatin, which is a representative cytotoxic agent for most cancer treatment. This study was designed to examine whether CNP pre-treatment attenuates tissue injury including acute renal failure induced by cisplatin.We used C57/B6 mice which were pre-treated with saline or CNP  and administered intraperitoneally a dose of 20 mg/kg cisplatin as the experimental acute renal failure mode. CNP infusion was started one day before the administration of cisplatin. This dose does not change blood pressure and heart rate in mice. At 72 hours after cisplatin injection, urine, blood and kidney samples were collected. Urine and blood samples were examined biochemically. Histological findings and gene expression in kidney tissue were evaluated.CNP reduced histological renal tubular damage and apoptosis induced by cisplatin, and suppressed plasma blood urea nitrogen  and creatinine levels , which were elevated by cisplatin administration. CNP treatment decreased the expression of kidney injury molecule-1  and monocyte chemoattractant protein-1 , which were elevated in the kidney by cisplatin administration. CNP treatment attenuated the decrease in GC-B expression in cisplatin-induced kidney injury.The present study is the first to show that CNP inhibits nephrotoxicity and kidney cell damage induced by cisplatin. Our data provide novel insights into the prophylactic therapy for various side effects induced by cytotoxic chemotherapy in many cancer patients.


The objective of this study is to assess correlation between bladder wall mechanical properties obtained by ultrasound bladder vibrometry (UBV) and urodynamic study (UDS) measurements in a group of patients undergoing clinical UDS procedure.Pdet) values. Mean, median and standard deviation of correlation values were calculated and the significance of these observations was tested.Concurrent UBV and UDS were performed on 70 patients with neurogenic bladders . Bladder wall mechanical properties measured by UBV at different filling volumes were correlated with recorded detrusor pressure . The correlation of group velocity squared and elasticity with Pdet were both significantly higher than 0.5.Bladder wall mechanical properties obtained by UBV as group velocity squared and elasticity showed high correlations with The results of this study suggest that UBV can closely monitor changes in bladder wall mechanical properties at different volumes in a group of patients undergoing UDS. The high correlation between UBV parameters and detrusor pressure measurements suggests that UBV can be utilized as a reliable and cost-effective tool for assessment of the bladder wall mechanical changes in a noninvasive fashion. Proper functionality of the human urinary system highly depends on bladder compliance. The heterogeneous combination of a smooth muscle layer and fibrous connective tissues provides a stretching capability which is essential for unidirectional flow of the urine from renal tracks, adequate storage of the urine and activation of the neural system for volunteer voiding . A numbePdet) via two pressure sensing catheters. By analyzing the results of UDS, physicians are able to observe the bladder’s physiological and neurological response to excess fluid at different volumes. Information such as leak points, bladder overactivity, and bladder compliance  can be immediately derived from such analysis [Currently, the urodynamic study (UDS) is the clinical routine for such examination. One of the main components of UDS is the study of bladder detrusor compliance via gradual filling of the bladder through an intravesical catheter and simultaneous measurement of the detrusor pressure  as a potential biomarker for predicting different diseases and pathological conditions such as breast cancer and malignant thyroid nodules –16. In tIn this study, we present the results of UBV in a group of patients undergoing UDS. The aim of this study is to establish the relationship between UBV measurements of the bladder mechanical properties and UDS outcomes in terms of detrusor pressures at different filling volumes. We use statistical analysis tools to show the strength of this relationship and discuss the utility of UBV as a novel, noninvasive and versatile technique for fast and accurate assessment of the bladder wall mechanical state.h, wave dispersion can be described using the following characteristic equationkL = ω/cp is the Lamb wave number, ω is the angular frequency, cp is the Lamb wave phase velocity, ρ is the tissue density, μ is the complex shear modulus (μ = μ1 + iμ2) [Human bladder can be modelled as an expandable viscoelastic thin shell immersed in and filled with incompressible fluid . Mechani1 + iμ2) .μ hereafter.High speed imaging of the tissue vibrations in response to radiation force enables tracking of the particle displacement from which group velocity and phase velocity dispersion can be obtained . The ana2O was considered compliant and the bladder with compliance < 40ml/cmH2O was considered as noncompliant.Standard UDS consists of bladder catheterization through the urethra for gradual filling and simultaneous measurement of the intravesical pressure by a pressure sensor. An additional sensor is used to measure the pressure outside the bladder  . The netAdult patients with neurogenic bladder referring to Mayo Clinic urology department for routine UDS were recruited for UBV study. The study was approved by the Mayo Clinic institutional review board (IRB), and written consent was obtained from patients prior to the examination.μ.A programmable ultrasound machine, Verasonics system  equipped with a curved linear array  with center frequency of 2.5 MHz was used. UDS bladder filling was performed at 50ml increments and at each volume two UBV measurements were performed. The filling rate was set based on standard clinical procedure guidelines  that recμ.For each patient, at each incremental filling volume, bladder wall mechanical properties in terms of Lamb wave group velocity squared and shear elasticity were calculated using UBV method. At each cystometric volume, the corresponding detrusor pressure reading was collected from the UDS. Wall mechanical properties were then correlated with the UDS detrusor pressure data using Pearson correlation. A student t-test was used to analyze the significance of correlations between UBV parameters and UDS detrusor pressure. All statistical analyses were performed in MedCalc ver. 15.8 .Seventy patients, 56 male and 14 female, were included in this study. Mean age was 52.19±15.9 years and mean body mass index (BMI) was 25.91±4.32.The median cystometry filling volume was 438.5ml (CI: 398.66–486.81) and mean was 415.93ml (CI: 387.28–444.57). The study ended at 500ml for 19 (27%) patients and 6 (8%) patients could not maintain more than 250ml due to early leaking. Pdet, and group velocity squared and shear elasticity, repsectively.Corr acquired from 70 patients. A summary of the statistical analysis of correlation values between UBV parameters and UDS detrusor pressure is presented in In this study we examined the correlation of bladder wall mechanical properties measured by ultrasound bladder vibrometry with UDS detrusor pressures measured at different cystometric volumes. The first step in UBV is to find the bladder wall using conventional B-mode ultrasound imaging. Our study showed that in most cases, bladder wall can be easily detected on the ultrasound images, even at low filling volumes. Using acoustic radiation force-based excitation followed by high frame rate imaging we were able to excite transient waves and track both their group velocity and phase velocity. The latter was used for a dispersion analysis from which elasticity was acquired. Our results showed strong correlation between group velocity squared and elasticity with detrusor pressure where median correlations were higher than 0.70. It was further observed that, group velocity squared and elasticity present similar correlations with detrusor pressure, with more statistical dispersions observed in the elasticity correlation data compared to the group velocity squared . This caOne limitation of our study was that UBV measurements were acquired only at incremental volume points rather than continuously. Hence, short-term changes in bladder physiological or neurological state, such as contractions and overactivity, might not be adequately captured using this setup. A more versatile implementation of UBV with the capability of continuously monitoring the bladder wall with filling volume is a future aim as an extension of the current method to address this issue. Moreover, continuous monitoring of elasticity would enable time-dependent analysis of the bladder’s physiological and neurological state via analysis of the elasticity parameters in form of linear and nonlinear time series similar to methods in , 24.The overall results of this study prove the suitability of UBV as an alternative technique for fast an accurate assessment of the bladder physiological and neurological conditions in terms of mechanical compliance. This method is especially attractive for patients who frequently require undergoing UDS due to a high risk of rapid bladder deterioration or due to closer monitoring purposes in response to different medications. UDS requires catheterization for both filling the bladder and measuring the detrusor pressure. UBV parameters, on the other hand, can be obtained noninvasively. Furthermore, for patients who have the capability to void voluntarily, UBV can be conducted through natural filling of the bladder and fractional voiding. This method has shown to be feasible in a previous study  on healtThe results of this study show that UBV parameters were significantly correlated with UDS measurements of the detrusor pressure, hence UBV may serve as a surrogate for accurate evaluation of the bladder detrusor state in a noninvasive fashion. The entire procedure is based on ultrasound which can be easily translated to the clinical setup using currently available ultrasound machines. This new technique can provide the flexibility to assess the bladder detrusor state in shorter time intervals with lower cost and ease of operation.


Infusion therapy is one of the most frequently prescribed medications in hospitalized patients. Currently used crystalloid solutes have a variable composition and may therefore influence acid-base status, intracellular and extracellular water content and plasma electrolyte compositions and have a major impact on organ function and outcome. The aim of our study was to investigate whether use of acetate-based balanced crystalloids leads to better hemodynamic stability compared to 0.9% saline.We performed a sub-analysis of a prospective, randomized, controlled trial comparing effects of 0.9% saline or an acetate-buffered, balanced crystalloid during the perioperative period in patients with end-stage renal disease undergoing cadaveric renal transplantation. Need for catecholamine therapy and blood pressure were the primary measures.p = 0.027; 68 ± 45 µg/kg versus 75 ± 60 µg/kg, p = 0.0055 and 0.000492 µg/kg body weight/min, ±0.002311 versus 0.000107 µg/kg/min, ±0.00039, p = 0.04, respectively). Mean minimum arterial blood pressure was significantly lower in patients randomized to 0.9% saline than in patients receiving the balanced infusion solution .A total of 150 patients were included in the study of which 76 were randomized to 0.9% saline while 74 received an acetate-buffered balanced crystalloid. Noradrenaline for cardiocirculatory support during surgery was significantly more often administered in the normal saline group, given earlier and with a higher cumulative dose compared to patients receiving an acetate-buffered balanced crystalloid (30% versus 15%, The use of an acetate-buffered, balanced infusion solution results in reduced need for use of catecholamines and cumulative catecholamine dose for hemodynamic support and in less occurrence of arterial hypotension in the perioperative period. Further research in the field is strongly encouraged. Infusion therapy is one of the most frequently prescribed medications in hospitalized patients. The importance of research on fluid therapy has been unrecognized for a long time with normal saline being the most popular infusate –4. DurinIn the present study we performed a sub-analysis using data from our previously performed prospective randomized controlled trial comparing an acetate-buffered balanced infusion solution compared to 0.9% saline in patients with end-stage renal disease receiving cadaveric renal transplantation . Our aimThe study was conducted at the Clinic of General Anesthesiology, Intensive Care and Pain Medicine of the Medical University of Vienna.All patients with end-stage renal disease undergoing cadaveric renal transplantation were included in the study. Patients younger than 18 years were excluded from the study as well as patients with a preoperative potassium concentration of more than 5.5 mmol/l. Enrollment started on 1 June 2010 and terminated on 28 February 2013. Prior to enrollment the study was registered at clinicaltrial.org (NCT01075750).+ 154 mmol/L, Cl− 154 mmol/L) or a chloride-reduced, acetate-buffered balanced crystalloid . No intravenous fluid was given prior to randomization. The following data were obtained from patients: age, sex, height, actual weight, dry weight, residual daily urine output, number of prior renal transplantations, total of fluid administered intraoperatively, total of fluid at start catecholamines, use of catecholamines, dose of catecholamines per kg body weight per min, time on catecholamines and cumulative vasopressor dose per kg body weight per min.Computer-based randomization was performed at time of transfer to the preoperative care unit of the Department of Anesthesiology. Patients either received normal saline  was infused. Hypotension was defined as a mean arterial pressure of less than 60 mm Hg. If hypotension occurred a fluid challenge with 250 ml of infusate was conducted. Additional fluid boluses of 250 ml were administered depending on volume reactivity . If no reaction to volume challenge was seen a vasopressor (either phenylephrine or etilefrine) was administered. A maximum dose of 0.1 mg of phenylephrine and 2 mg of etilefrine was given at one time. If more than ten applications of vasopressor were necessary per hour or likely to exceed ten applications per hour (severe refractory hypotension) noradrenaline infusion was commenced. Additionally, repeated fluid boluses were administered if considered necessary by the anesthesiologist.The study was approved by the local institutional review board , of the Medical University of Vienna, Austria, and registered at a clinical trials registry (NCT01075750). Written informed consent was obtained from every patient included in the study.2-test.The sample size calculation for the original study is described in detail elsewhere . StatistP < 0.05.In order to test whether mean arterial blood pressure differed between the saline group and the acetate-buffered balanced crystalloid group, we used a generalized estimating equation assuming a normal probability distribution and a first order exponential correlation matrix for repeated observations in one patient. In order to test for differences in the incidence of vasopressor administration between the two study groups, we used a log-rank test and a Kaplan-Meier plot for visualization. In order to test whether vasopressor use was anteceded by hypotension, we used a Cox regression with vasopressor use as the dependent variable and mean arterial blood pressure as the time varying predictor variable. For all analyses statistical significance was defined by a two-sided Figures were drawn using GraphPadPrism 5.01.A total of 150 patients were included in the study, 76 patients were randomized to normal saline and 74 patients to an acetate-buffered balanced crystalloid. No differences between the groups were found for the following parameters: age, sex, height, actual and dry weight, residual daily urine output, number of prior renal transplantations. For an overview on baseline characteristics see Table p = 0.34). Noradrenaline for cardiocirculatory support during surgery was administered significantly more often in the normal saline group compared to patients receiving an acetate-buffered balanced crystalloid . Patients receiving normal saline needed noradrenaline significantly earlier and the cumulative noradrenaline dose was significantly higher than patients receiving an acetate-based crystalloid solute . No difference in necessity for vasopressor or cumulative dose of vasopressors was seen between the groups  . Consequently, mean minimum systolic  and mean minimum diastolic blood pressure  were significantly lower in patients randomized to 0.9% saline. Patients randomized to 0.9% saline over time had a mean arterial blood pressure, which was 4 mm Hg lower than in patients receiving an acetate-buffered balanced solution during whole surgery . Fig. p = 0.66) and central venous pressure  between the groups.Mean minimum arterial blood pressure was significantly lower in patients randomized to 0.9% saline than in patients receiving the balanced infusion solution , p = 0.03. Serum sodium levels were not significantly different between the groups (4 mmol/L [3 to 5] versus 3 mmol/L [2 to 5]), p = 0.92. Acid base disturbances are described in more detail elsewhere [Peak chloride levels were significantly higher in patients randomized to the normal saline group (109 mmol/L [107 to 111] versus 107 mmol/L [105 to 109]), lsewhere .These are the first data from a prospective, randomized, controlled study comparing the effects of 0.9% saline and an acetate-buffered balanced crystalloid solution on hemodynamics in the perioperative period. We showed that perioperative use of a balanced crystalloid as a maintenance fluid is associated with better hemodynamic stability of patients with end-stage renal disease receiving cadaveric renal transplantation. These findings are expressed by a significantly lower need for use of catecholamines for hemodynamic support and higher systolic and mean arterial blood pressure levels.The strength of the current study is explained by the study collective: all patients had end-stage renal disease and received cadaveric renal transplantation. This collective of patients is especially vulnerable to effects due to infusion solutions since they lack the capacity of the kidneys to rapidly compensate for electrolyte and acid-base derangements to a variable degree. Theoretically, this makes even slight effects due to the infusion solution obvious, which would not be seen in patients with normal kidney function or only after administration of far larger volumes of fluid.We found a significantly lower need for catecholamines, a longer time to catecholamines and a lower cumulative catecholamine dose in the acetate-buffered group. The significantly better hemodynamic stability in patients receiving a balanced acetate-based infusate compared to normal saline might be related to A) acetate itself and B) hyperchloremia induced by normal saline.So far no study has compared the hemodynamic effects of normal saline to an acetate-buffered balanced crystalloid; however, there is some older evidence that the use of sodium acetate may have an influence on the cardiovascular system. In 1978 Liang and Lowenstein infused acetate and pyruvate in to anesthetized dogs to measure their impact on circulation . They foIn 2004 the study group around John Kellum showed in a model of experimental sepsis that infusion of chloride-rich crystalloids led to a decrease in arterial blood pressure in rodents compared to infusion of lactated Ringers . In anotOur study has several limitations. The major drawback of this study is the lack of invasive hemodynamic monitoring such as esophagus Doppler, pulmonary artery catheter or thermodilution techniques. Additionally, blood pressure was monitored non-invasively, which was performed in order to preserve blood vessels in patients potentially in need of dialysis shunts in the future. Additionally, it has to be borne in mind that the original study was designed to investigate incidence rates of perioperative hyperkalemia, other electrolyte and acid-base disorders and not hemodynamics. Therefore, hemodynamic management followed hospital standard operating protocols (SOP but not a hemodynamic protocol specially designed for the present study. Additionally, the study was not blinded, so investigator bias is possible but not very likely as hemodynamics were not an outcome in the first study and hospital SOP’s were followed. Nonetheless the results of the present study should be interpreted with some caution. We see our results as a first indiction that the choice of crystalloid may impact hemodynamic stability, but certainly further research needs to be done before an overall conclusion can be reached.In conclusion, the results of the prospective, randomized, controlled trial suggest that use of an acetate-buffered, balanced infusion solution results in less occurrence of arterial hypotension and reduced need for use of catecholamines and cumulative catecholamine dose for hemodynamic support in the perioperative period. The more favorable hemodynamic outcome of patients receiving an acetate-buffered crystalloid solute may be attributed to increased cardiac output related to acetate as well as lower susceptibility for hyperchloremia and concurrent metabolic acidosis when compared to normal saline. Future randomized, controlled trials are certainly desirable to clarify the effects of current crystalloid infusates on hemodynamics in the perioperative field and the critically ill.


Fluid responsiveness (FR) was defined as an increase of 20% or greater in cardiac index, measured by FloTrac-Vigileo®. Dynamic preload variables  were recorded additionally. Pvr, the driving pressure for venous return  and heart performance  were calculated according to standard formula. Pmsa increased following fluid administration in responders  and in non-responders . Pvr, which was lower in responders before fluid administration , increased after fluid administration only in responders . EH only decreased in non-responders . The area under the receiver operating characteristics curve of Pvr, PPV and SVV for predicting FR was 0.75, 0.73 and 0.72, respectively. Changes in Pmsa, Pvr and EH reflect changes in effective circulating volume and heart performance following fluid resuscitation, providing a physiologic discrimination between responders and non-responders. Also, Pvr predicts FR equivalently compared to PPV and SVV, and might therefore aid in predicting FR in case dynamic preload variables cannot be used.To assess the significance of an analogue of the mean systemic filling pressure (Pmsa) and its derived variables, in providing a physiology based discrimination between responders and non-responders to fluid resuscitation during liver surgery. A post-hoc analysis of data from 30 patients undergoing major hepatic surgery was performed. Patients received 15 ml kg H), which is defined as Pvr/Pmsa, and yields a dimensionless variable ranging from 0 to 1. The significance of Pmsa, Pvr and EH in FR compared to dynamic preload variables still have to be investigated.The basis of hemodynamic management in critically ill patients and in patients undergoing major surgery is formed by a rational titration of fluids, vasopressors and inotropes, with the ultimate goal to maintain sufficient tissue oxygen delivery . In receH following fluid administration to allow a further physiologically based differentiation between fluid responders and non-responders.Therefore, the aim of this study was to evaluate the changes in Pvr, PPV and SVV in both responders and non-responders to fluid administration. Secondly, we aimed to elucidate the changes in Pmsa, Pvr and E−1 fluid bolus directly after completion of hepatic resection. In accordance with the Helsinki declaration, the original study was approved by the local medical ethics committee  and has been registered at clinicaltrials.gov (NCT01060683). Only ASA I—III patients who were scheduled for major hepatic resection were included after written informed consent had been obtained. Given that the current study represents a post-hoc analysis of de-identified data from a non-public database, no additional approval of the medical ethics committee or additional written informed consent was obtained.The current study is a post-hoc analysis of a randomized controlled trial performed in 30 patients undergoing major hepatic resection in whom we investigated the reliability of non-invasive measurement of hemoglobin concentration  and the In the original study, cardiac output-based data were obtained as part of routine clinical monitoring. Furthermore, each patient served as his/her own control.Patients were excluded in case of intra-operatively diagnosed incurable disease, cardiac dysrhythmia or requirement of additional intravenous fluids to maintain hemodynamic stability before the fluid bolus was administered  .−1 lean body mass, with PEEP set at 5 cmH2O. The dosage of continuously adminstered norepinephrine was titrated to keep MAP between 60 and 80 mmHg. During the phase of hepatic resection, all patients received 6 ml kg−1 hr−1 crystalloids  as baseline infusion. After completion of hepatic  resection—but before surgical closure of the abdomen—patients were allocated to receive a 15 ml kg−1 fluid bolus of either crystalloids (n = 15) or colloids (n = 15) in a fixed time frame of 30 min.All patients received a standardized balanced general anesthesia after placement of a thoracic epidural catheter, as previously described , 22. PatFR was defined as an increase in CO, indexed to BSA  by at least 20% after fluid administration. A higher-than-normal definition of FR was applied because of both the relatively large amount of fluid administered during the resuscitation phase and the increased discriminative ability of dynamic variables to predict FR in case of higher FR thresholds .All measurements took place during the 30 min period of fluid administration.® device  was connected to the arterial pressure transducer for continuous calculation of CO using an automated auto-calibrated analysis of the arterial pressure waveform. Additionally, this device calculates stroke volume variation (SVV) over a 20 s period using the formula: MAP was monitored invasively using a 20 G radial artery catheter and the pressure transducer was connected to the vital signs monitor . The FloTrac-VigileoCVP was continuously recorded after cannulation of the right internal jugular vein using a 7 F triple lumen catheter. Both the arterial and central venous pressure transducers were zeroed and thereafter adjusted to the height of the right atrium.The calculation of Pmsa is based on the Parkin algorithm , which formation . Pmsa hamentclasspt{minimaormation .Handling of data recording of the hemodynamic data was described previously . All datt-test. Non-normally distributed data were tested using the (paired) Mann–Whitney test or (unpaired) Kruskal–Wallis test.Continuous variables were tested for normal distribution using the Kolmogorov–Smirnoff test. Normally distributed variables were tested using the paired or unpaired Student’s Correlation between relevant variables was depicted as a scatter plot and coefficients of determination  were calculated.The ability of dynamic preload variables and Pvr to predict FR was assessed using receiver operating characteristic (ROC) analysis. The areas under the ROC curve (AUROC’s) were compared using the DeLong methodology .Statistical significance was set at p < 0.05. Data are presented as mean ± standard deviation.A total of 30 patients  received a fluid bolus and were included for analysis. Mean age of all patients was 57 ± 13 years, mean height and weight were 176 ± 7 cm and 80 ± 13 kg, respectively.18/30 patients demonstrated an increase in CI > 20% and were regarded as fluid responders; consequently, 12/30 patients were regarded as non-responders.Hemodynamic variables at baseline and after fluid administration are summarized in Table Pmsa was comparable between responders and non-responders at baseline  was lower in responders than in non-responders at baseline . Moreover, Pvr only increased in responders  after fluid administration. In Fig. H) was comparable between responders (0.52 ± 0.11) and non-responders (0.56 ± 0.17) at baseline (p = 0.47). Importantly, EH decreased following fluid administration in non-responders to 0.45 ± 0.12 (p < 0.01) but remained stable in the responders group . The resistance to venous return (RVR) did not differ between both groups at baseline. In responders, RVR decreased after fluid administration [from 2.5 ± 0.6 to 2.1 ± 0.4 mmHg min−1  m−2 L−1  (p < 0.01)], while it remained unchanged in non-responders.Heart Performance , which was also true after fluid administration .Norepinephrine dosages at baseline were not significantly correlated with Pmsa, Pvr, RVR or EThe AUROC of Pvr in predicting FR was 0.75 : 0.57–0.93; p < 0.05, Fig. There were no significant differences between the observed AUROC’s. The optimal cut-off value for Pvr was 7 mmHg with an associated sensitivity and specificity of 72% and 75%, respectively. The optimal cut-off values for PPV and SVV were 14% and 16% respectively, with associated sensitivity and specificity values of 83/58% and 56/91%, respectively.H to predict FR was not significant .Of note, the AUROC of Pmsa and E2 = 0.37; p < 0.01, Fig. 2 = 0.93; p < 0.01; Fig. 2 0.18, p < 0.01), whereas ∆PPV did not  .There was a moderate correlation between Pvr and CI at baseline  increased which led to an increase in CI. In other words, the heart was able to generate more output from the increase in venous return. In non-responders, CVP increased to a similar extent as Pmsa and the increase in CVP helps reducing venous return.H, decreased as the heart was unable to handle the increase in venous return, while in responders EH remaine stable, i.e. the efficiency of the heart in handling an increase in venous return was maintained.Importantly, ESecondly, the observation that PPV, SVV and Pvr predict FR equivalently, might suggest that Pvr can be used alternatively for the prediction of FR in case the former variables cannot be used.CO is determined by the effective circulating blood volume (ECBV), the resistance to venous return and the pressure within the right atrium . Pmsa, aH (Pvr/Pmsa) reflects the Pvr—Pmsa relationship: it decreased significantly in non-responders, but remained unchanged in responders. As explained above, this observation might indicate that in these patients the heart was unable to handle the increase in Pmsa and thus, these patients did not benefit from fluid, i.e. these patients were likely to be  on the “flat” part of their Frank-Starling curve. We therefore speculate that this variable might be used clinically to monitor the effects of fluid administration on cardiac performance itself. Potentially, EH might also demonstrate the (combined) effects of fluid administration and other factors such as inotropic medication on cardiac performance. Future studies should confirm the potential use of EH. Interestingly—as patients were randomized to receive either crystalloids or colloids—we found no differences in Pmsa or derived FR variables between these groups. Given the controversial differences between the intravascular effects of these fluids, this finding might be contrary to expectations, although this post-hoc analysis was not set up to study differences between fluid types, and studying these effects probably requires a larger sample size.EWe observed a decrease in RVR (Pvr/CI) in responders, which is likely given that RVR will decrease if the increase in CI exceeds the increase in Pvr. This observation however contrasts previous reports in which RVR remained stable after either changes in norepinephrine dosage in septic shock patients  or afterisolated pressure values such as Pmsa are inadequate predictors of FR, as demonstrated by an AUROC of 0.48 in our study. These static variables should therefore not be used solely [Currently, in sedated and mechanically ventilated patients, dynamic (preload) variables like PPV and SVV are established predictors of FR—both perioperatively and in the ICU—and these variables have been found superior to static variables like CVP and pulmonary capillary wedge pressure –5, 28–30d solely  as a surd solely .one definition of FR (i.e. an increase of CI > 20%), while we have recently shown [Interestingly, the ability to predict FR by dynamic preload variables was lower than generally reported in literature , 30, evely shown  that thely shown  in the sThere are no recommendations for an “optimal” Pvr value for guiding fluid management: as an example, a Pvr of 5 mmHg can result from multiple combinations of Pmsa and CVP, such as 10/5 mmHg and 20/15 mmHg, respectively. In these instances, it is questionable whether CI will increase to a similar extent. Therefore, future studies in large, perioperative patient populations or in critically ill patients should verify the assumed role of Pvr in predicting FR. Of note, a recent study in post-cardiac surgery patients suggested using the ratio between changes in Pvr and changes in Pmsa—called “volume efficiency”—as an additional predictor of FR .H, has not yet been the subject of investigation in any (early) GDFT trial. Therefore, it remains to be elucidated—as was also recently suggested [Also, the usefulness of variables such as Pvr and Euggested —whether mathematical approach to estimate Pmsf—which is inherently coupled to CO—it is likely that assessing Pmsf using other methods would have produced similar results. Importantly, this issue requires further research.Pmsf is a theoretical variable that cannot be measured clinically to assess its validity, as real-life measurement would require circulatory arrest . The calIt has been shown previously in septic shock patients that norepinephrine titration influences venous return by exerting effects on Pmsf and resistance to venous return . In our Finally, the applied algorithm incorporates hemodynamic values and combines these with demographic parameters in order to calculate Pmsa and subsequent calculation of Pvr. As the algorithm for calculation of Pmsa is based on multiple (independent) measurements , the measurement error of Pmsa is an accumulation of the individual measurement errors of each variable, e.g. due to variation in the location of tip of the central venous catheter. For the latter, we verified post-hoc the correct positioning of the central venous catheter in all patients.H allow a physiology-based differentiation between responders and non-responders to fluid administration. Also, the ability of Pvr to predict FR was similar to that of PVV and SVV and therefore, Pvr might be used as an alternative method for predicting FR, especially in situations in which PPV or SVV are deemed unreliable.In conclusion, bedside calculation of Pmsa, Pvr and E


Although the relationship between hyperparathyroidism and hypertension has been described for decades, the role of hyperparathyroidism in hypertension in dialysis is still unclear. Following the case of a severely hypertensive dialysis patient, in which parathyroidectomy (PTX) corrected the metabolic imbalance and normalized blood pressure (BP), we tried to contextualize our observation with a systematic review of the recent literature on the effect of PTX on BP.A dialysis patient, aged 19 years at the time of this report, with chronic kidney disease (CKD) from childhood; he was an early-preterm baby with very low birth weight (910 g), and is affected by a so-far unidentified familial nephropathy. He started dialysis in emergency at the age of 17. Except for low-dose Bisoprolol, he refused all chronic medication; hypertension (165–200/90–130 mmHg) did not respond to attainment of dry weight . He underwent subtotal PTX 1 year after dialysis start; after PTX, his blood pressure stabilized in the 100–140/50–80 range, and is normal without treatment 5 months later.Our patient has some peculiar features: he is young, has a non-immunologic disease, poor compliance to drug therapy, excellent dialysis efficiency. His lack of compliance allows observing the effect of PTX on BP without pharmacologic interference.The prompt, complete and long-lasting BP normalization led us to systematic review the current literature  retrieving 8 case series (194 cases), and one case report (3 patients).The meta-analysis showed a significant, albeit moderate, improvement in BP after PTX (difference: systolic BP -8.49 (CI 2.21–14.58) mmHg; diastolic BP -4.14 (CI 1.45–6.84) mmHg); analysis is not fully conclusive due to lack of information on anti-hypertensive agents. The 3 cases reported displayed a sharp reduction in BP after PTX.In summary, PTX may have a positive influence on BP control, and may result in complete correction or even hypotension in some patients. The potential clinical relevance of this relationship warrants prospective large-scale studies. Hyperparathyroidism has long been associated with arterial hypertension , 2. The If excess PTH induces hypertension, a decline in blood pressure should follow ablation of parathyroid function in dialysis patients with severe hyperparathyroidism and hypertension. Overall, the data suggest that, at least in selected patients, parathyroidectomy (PTX) is associated with an improvement in blood pressure control –13. HoweThe practice of PTX in dialysis patients has changed over time. While in the past surgery often represented the only way to correct a severe metabolic imbalance in the context of hyperparathyroidism, improvements in dialysis efficacy, and the new generations of drugs active on the Ca-Phosphate-PTH axis have sharply reduced the need for PTX. The issue is however still open, and in recent years a number of large studies have suggested reconsidering PTX, not only for the immediate metabolic advantages it produces, but also because of an apparent survival advantage in patients who underwent surgical correction –23.In this context, several recent studies addressed the relationship between cardiovascular diseases and PTX. While a positive effect on overall cardiovascular status is reported in many large series, some papers considered the unsolved issue of the relationship between hyperparathyroidism and elevated blood pressure in dialysis patients, once more leading to controversial results , 13, 17.It is in this context that we would like to report on an emblematic case, a young dialysis patient whose severe hypertension was fully corrected by PTX, and review the recent literature on this subject, to underline the importance of this intriguing relationship, which is rarely adequately taken into account in current clinical practice.A young dialysis patient, aged 19 years at the time of the present report. Chronic kidney disease (CKD) was evident from childhood: at 9 years of age his serum creatinine was 1.04 mg/dL (92 μmol/L). The patient was an early-preterm baby (born at 30 weeks) with very low birth weight (910 g), both elements associated with an increased risk of developing several metabolic diseases including CKD .He is affected by a so far unidentified familial kidney disease: his 57-year-old mother has Stage 4 CKD and his sister underwent preemptive kidney transplantation at the age of 22. In all family members CKD is characterized by low-grade proteinuria, relatively high uric acid levels, and no microhematuria, consistent with the hypothesis of an interstitial nephropathy. The family history is marked by low compliance with treatments and controls, and a precise characterization of the genetic disease has not yet been possible. A search for mutations of UMOD and REN, and the enzyme assessment for Fabry’s disease, tested negative; HLA-B27 is negative; his karyotype is normal and no other clinical element suggested other common monogenic nephropathy . Genetic reevaluation is on-going.The patient started dialysis in emergency at the age of 17, in the presence of extreme uremia and generalized edema. At referral, his serum creatinine was 18.43 mg/dl (1630 umol/l), urea 524.32 mg/dl (87.3 mmol/l), bicarbonate 13 mmol/l, potassium 3.8 mmol/l, hemoglobin level 6.1 g/dl, BNP > 4000 pg/ml. In keeping with a chronic, non-compensated end-stage kidney disease, PTH was extremely elevated (> 1500 ng/l), with normal calcium and high phosphate levels , which we hoped could at least partially ameliorate his severe hypertension, the patient took no chronic medications.His blood pressure did not decrease during dialysis, although he had no clinical sign of chronic overload, no radiological sign of pulmonary overload, no oedema and normal BNP levels . His usual weight gain between sessions was 1.5–2.5 Kg, and did not change before and after parathyroidectomy.At time of dialysis start, his echocardiography showed non obstructive homogenous left ventricular hypertrophy with an ejection fraction of 35–40% and small circumferential pericardial effusion. The ejection fraction was restored 1 year after dialysis start (50%), shortly before the parathyroidectomy and the left ventricular hypertrophy regressed (116 g/m2 versus 172 g/m2). Due to the essential normalisation of the picture, a further control was not performed after parathyroidectomy, and is scheduled 2 years after the previous one.All viral and immunologic tests  tested negative at referral (with the exception of smooth muscle antibodies at low titer: 1/200). The results were confirmed at a further recent control.His predialysis blood pressure range, in the last month before parathyroidectomy was 165–200/90–130 mmHg, while post dialysis it was 170–190/80–100 mmHg.His usual weight gain between sessions was 1.5–2.5 Kg, and did not change before and after parathyroidectomy.Lack of compliance with the chronic treatment was not accompanied by lack of compliance with dialysis. In fact, he never missed a dialysis session, nor did he ever shorten dialysis time. It should be noted that his dialysis efficiency was over target, and his nutritional status was good. His chronic dialysis data are summarized in Table The patient’s parathyroid hormone levels remained high > 1500 ng/l) and he developed hypercalcemia after the start of chronic dialysis. These alterations did not respond to dialysis treatment ; he did not take Cinacalcet, as prescribed, and his PTH decreased only partially during dialysis, in spite of hypercalcemia at the end of treatment , suggesting secondary-tertiary hyperparathyroidism. Parathyroid scintigraphy was compatible with the presence of bilateral inferior parathyroid adenomas  and small oxyphilic cells, with no atypia or mitosis. His calcium and PTH values dropped , and he developed a symptomatic hungry bone syndrome  was performed using Metanalyst Beta 3.13, for the outcome blood pressure.The search strategy identified 286 articles, of which 9 met the inclusion criteria: 1 case report, 5 retrospective studies and 3 prospective studies, dealing with a total of 187 patients , but non-homogenous for the setting of the study (five from Asia and four from Europe) for indications for parathyroidectomy, and selection of patients. For example, in the study by Lin, PTX was recommended for severe secondary hyperparathyroidism defined as PTH level higher than 800 pg/ml associated with bone or joint pain, muscle weakness, irritability, itching, bone loss, anemia resistant to erythropoietin, cardiomyopathy or calciphylaxis . InsteadOverall, within the baseline heterogeneity, a trend towards an improvement in BP control was observed in most case series: 6/8 papers Table . FurtherThe meta-analysis showed a significant, albeit moderate improvement. in particular in systolic BP (difference: systolic BP 8.49 (CI 2.21–14.58) mmHg; diastolic BP decrease, 4.14 (CI 1.45–6.84) mmHg was significant albeit of a lesser degree Fig. .Fig. 3MeOur evaluation of the effect on blood pressure was limited by the lack of clear information on anti-hypertensive agents, which have probably been reduced in a relevant number of cases, as judged from the comments in the papers by Shih, Esposito and Chow Table .The case described has features that make it an interesting example of the complex relationship between severe hyperparathyroidism and hypertension.The patient is young and has a non-immunologic disease. His compliance with drug therapy was poor, while his compliance with dialysis treatment was excellent. Tests for the cause of a so far uncharacterized interstitial disease identified no immunologic interference. His lack of compliance with chronic treatments allowed us to observe the effect of the metabolic derangements and of their correction on his blood pressure pattern without the interference of pharmacologic treatment and his good compliance with dialysis enabled us to analyze the effect of PTX without the interference of a low dialysis dose.The prompt, complete and long-lasting normalization of blood pressure was unexpected, and this led us to review the current literature, so that we could contextualize our case and reflect on whether and how this positive effect of treatment could be expected in similar situations.The relationship between hyperparathyroidism and hypertension in dialysis patients was reported in the 1980s and 1990s, albeit with conflicting results: Ifudu showed that in hypertensive dialysis patients PTX failed to correct hypertension, suggesting a minor effect of PTH in dialysis hypertension at least in relation to volume overload . ZucchelRecent data confirm the pathogenic effect of hyperparathyroidism, elucidating the molecular effects and clearly indicating that vascular stiffness is not only mediated by calcium and phosphate accumulation, but also by PTH itself, via PTH2 receptors –27. ElevUnlike the elegant pathophysiologic studies, the recent data on blood pressure before and after PTX, which we gathered for our systematic review and meta-analysis, are highly heterogeneous and their interpretation is biased by a lack of precise information on concomitant drug therapy.However, the limited information available in most of the papers retrieved suggests that the positive effect on BP was recorded in the setting of equal or reduced anti-hypertensive doses, thus further underlining the clinical relevance of BP decrease after PTX –13, 15.In this context, within all the limits mentioned above, our meta-analysis allowed us to quantify the BP difference, which was higher for systolic BP (8.49 (CI 2.21–14.58) mmHg), in keeping with a reduction in vascular stiffness, and was significant, but of a lesser entity, for diastolic BP (4.14 (CI 1.45–6.84) mmHg).It is noteworthy that, in the only case report we were able to retrieve, the differences were more important and were abrupt, and the three cases described suggest that patients may actually shift from severe hypertension to symptomatic hypotension after PTX . A similOur review of the literature, within the limit of heterogeneity and of limited quality, suggests that PTX exerts a beneficial effect on blood pressure, leading to a significant decrease in both systolic and diastolic BP; the higher effect on systolic BP suggests a beneficial reduction of vascular stiffness. The results are however biased by the lack of information on drug therapy, an issue that should be addressed in future prospective studies.Our case, like the ones of three other patients reported in the literature, serves as a reminder that the effect on blood pressure is highly unpredictable. Full correction may occur, as it did in our patient, but even symptomatic hypotension sometimes, albeit rarely, has been found in patients after PTX. Further prospective studies are needed that better quantify the entity of the changes, the risk of extreme BP reduction and interference with pharmacologic treatment, to enable us to make use of these findings in our clinical judgments and counseling.


Ischemic ocular disorders may be treated by hypervolemic hemodilution. The presumed therapeutic benefit is based on a volume effect and improved rheological factors. The aim was to investigate the acute effect of intravenous hydroxyethyl starch on retrobulbar hemodynamics in patients with nonarteritic anterior ischemic optic neuropathy (NAION). 24 patients with acute NAION were included. Retrobulbar hemodynamics were measured using color Doppler imaging before and 15 min after intravenous infusion of 250 cc 10% hydroxyethyl starch (HES). Peak systolic velocity (PSV), end diastolic velocity (EDV), and Pourcelot's resistive index (RI) were measured in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (PCAs).p < 0.001); EDV from 2.16 ± 0.56 to 2.34 ± 0.55  (p < 0.05)) and in the PCAs (PSV from 7.18 ± 1.62 to 7.56 ± 1.55  (p < 0.01); EDV from 2.48 ± 0.55 to 2.66 ± 0.6 cm/sec (p < 0.01)). The RI of all retrobulbar vessels remained unaffected. Blood pressure and heart rate remained unchanged. After infusion of HES blood flow velocities significantly increased in the CRA (PSV from 7.53 ± 2.33 to 8.32 ± 2.51  (DRKS00012603. Hypervolemic hemodilution has an acute effect on blood flow velocities in the CRA and PCAs in NAION patients. Increased blood flow in the arteries supplying the optic nerve head may lead to a better perfusion in NAION patients. This trial is registered with  The etiology of nonarteritic anterior ischemic optic neuropathy (NAION) is believed to be multifactorial resulting in an acute hypoperfusion of short posterior ciliary arteries supplying the optic nerve , 2. The Several studies investigated circulatory abnormalities in ocular blood flow in patients with NAION. Prolonged arteriovenous passage times and significantly delayed filling of the optic nerve head capillaries in fluorescein angiography in NAION patients were reported , 10. FurIn NAION, an acute hypoperfusion of short posterior ciliary arteries results in optic nerve head ischemia leading to a sudden painless visual field defect with an optic disc edema. Multiple medical and surgical treatment options have been investigated, including levodopa , hyperbap = 0.024) [The effect of hemodilution in NAION using hydroxyethyl starch infusion was investigated in a prospective randomized study in 1991. The initial results showed an improvement of visual acuity three months after isovolemic hemodilution in six of eleven patients in comparison to one of ten patients in the control group = 0.024) . No long . No lon= 0.024) . In a reEven though placebo-controlled long-term studies of hemodilution therapy in NAION are missing, hypervolemic hemodilution using hydroxyethyl starch might be beneficial in the acute treatment resulting in improved blood flow in the optic nerve. In our department, the initial infusion of hydroxyethyl starch is immediately given after the diagnosis NAION has been confirmed as a standard clinical regimen followed by isovolemic hemodilution for 3–5 days. The present study investigates the acute effect of the initial hydroxyethyl starch infusion on retrobulbar hemodynamics in patients with NAION.DRKS00012603.Twenty-four consecutive patients (mean age: 67 ± 9 years) with nonarteritic unilateral AION were enrolled in this study. Patients were included if they presented a pathognomonic acute painless visual field loss and an optic disc edema without evidence of other neurological or ocular diseases. All patients were studied within 4 weeks of onset of visual field loss (mean latency: 7 days). The trial was registered with Patients with high erythrocyte sedimentation rate (ESR > 35/65 mm/hr) and increased C-reactive protein (CRP > 10 mg/l) or with clinical features of giant cell arteritis  were excluded from this study. Furthermore, exclusion criteria were contraindications to hydroxyethyl starch infusion like arterial blood pressure higher than 170/90 mmHg, chronic renal insufficiency, or known allergy against hydroxyethyl starch.Demographic and clinical data of the patients are given in All patients had a detailed ophthalmological examination and visual field testing with the Goldmann perimeter or the Humphrey Field Analyzer  using a white-on-white 30-2 program and color Doppler imaging examination (CDI). The visual acuity was given in logMAR. Patient's history was explored with special interest in cardiovascular risk factors .The eye, gender, and age of the patients and latency between onset of visual field loss and examination were registered. ESR, C-reactive protein, and creatinine were determined.The retrobulbar hemodynamics were measured before and 15 min after an intravenous infusion  of 250 cc 10% hydroxyethyl starch (molecular weight: 200.000/degree of substitution 0.5) within 30 min. The same testing conditions for the CDI measurements existed prior to and after the infusion. The investigation followed the tenets of the Declaration of Helsinki and was approved by the local ethics committee.Retrobulbar blood flow velocities of the ophthalmic artery (OA), the central retinal artery (CRA), and the temporal and nasal posterior ciliary arteries (PCAs) were determined by CDI by the same experienced investigator (MB) . A 7.5 MThe OA was examined approximately 25 mm behind the globe at the straighter portion of the vessel in the nasal orbit to obtain the most reliable results . The CRAHeart rate and blood pressure were determined by sphygmomanometry in a sitting position after a rest of 5 minutes before and 15 minutes after the infusion of hydroxyethyl starch . The mean arterial blood pressure was calculated as follows: mean arterial blood pressure = diastolic blood pressure + 1/3 (systolic blood pressure − diastolic blood pressure).t-test was applied for comparisons before and after hydroxyethyl starch. Correlations were calculated by Fisher's transformation. Fisher's exact test was used in the analysis of contingency tables. In all analyses, p < 0.05 was regarded as statistically significant.For the statistical analysis of this study, a paired Blood flow velocities and resistive indices of the patients with acute NAION before and after the infusion of 250 cc 10% hydroxyethyl starch are summarized in p < 0.001) and the EDV from 2.2 ± 0.6 to 2.3 ± 0.6 cm/sec (p < 0.05). In PCAs, the PSV rose from 7.2 ± 1.6 to 7.6 ± 1.6 cm/sec (p < 0.01) and the EDV from 2.5 ± 0.6 to 2.7 ± 0.6 cm/sec (p < 0.01). Please refer to Figures After infusion of hydroxyethyl starch the peak systolic and end diastolic blood flow velocities significantly increased in the CRA and PCAs compared to the pretreatment velocities. In CRA, the PSV increased from 7.5 ± 2.3 to 8.3 ± 2.5 cm/sec p < 0.00 and the r = −0.53, p < 0.01) and of the PSV in PCAs . The PSV in the CRA and the EDV in the PCAs showed no correlation between the relative change and the baseline velocity. No correlation between the relative changes and time to treatment was recorded.We found no correlation between the relative changes of retrobulbar blood flow velocities. However, there was a significant negative correlation between the relative change and the pretreatment velocity of the EDV in CRA  showed a relative change of EDV above the median (>4.94%). Fisher's exact p value was not significant (p = 0.22).For further analysis of changing velocities, contingency tables were calculated with two groups. The first group with a relative change of velocity more than the median and the second group with a relative change less than or equal to the median were determined. In the CRA, all patients with a relative change of PSV above the median (>9.35%) showed a relative change of EDV above the median (>5.61%). Fisher's exact The RI of all retrobulbar vessels remained unaffected. The OA showed no significant changes in any hemodynamic parameter after hypervolemic hemodilution. Blood pressure and heart rate remained unchanged .After hypervolemic hemodilution using hydroxyethyl starch, blood flow velocities in the CRA and the PCAs are significantly increased in acute NAION. Higher blood flow velocities measured by CDI may be interpreted as either an increase in blood flow, a lower peripheral resistance, or a decrease of vessel diameter. We did not find any changes of the resistive indices of the retrobulbar vessels after hydroxyethyl starch; therefore an increase in vessel resistance seems unlikely. Spencer et al. showed that simultaneous changes of the peak systolic velocity and end diastolic velocity of the CRA without changes of resistive indices may be interpreted as altered volumetric flow in this vessel . TherefoAn increase in flow velocities after hypervolemic hemodilution, presumed as a higher volumetric flow in the retrobulbar vessels, might be due to more than a volume effect alone. Patients with NAION showed a higher plasma viscosity in comparison to healthy controls  and HES Lately, HES solutions were critically reviewed and the marketing authorizations for the EU were withdrawn . AlthougOverall, it is not known if the use of HES is dangerous in NAION patients to date. The administration appears to be safe in these patients, who in most cases are not critically ill and do not end up in an intensive care unit; however the administration in patients with preexisting renal dysfunction and renal diseases appears questionable.In this study, we present increased blood flow velocities in the PCAs and CRA after hypervolemic hemodilution in patients with NAION. Negative correlations between the pretreatment velocity and the relative change were found in the EDV of CRA and in the PSV of PCAs, suggesting that patients with low velocities at baseline showed a higher increase of flow velocities compared to patients with higher pretreatment velocities. The acceleration of flow velocities by HES in the vessels with reduced blood flow might represent an improvement of the acute circulatory disorder in NAION.However, similar results of improved perfusion parameters were initially reported for optic nerve sheath fenestration (ONSF) . NeverthA limitation of this study is the different latencies between the onset of symptoms of NAION and the initiation of hemodilution. However, we found no correlation between the latency and the relative change of the velocities after treatment. Another limitation is a possible influence of antihypertensive drugs and systemic diseases on retrobulbar hemodynamics. Furthermore, the IOP was not measured after HES infusion; therefore, one can only speculate that the ocular perfusion pressure remained unaffected by the infusion. The systolic and diastolic blood pressure values remained stable after HES infusion.In conclusion, this study showed an acceleration of the peak systolic velocity and end diastolic velocity in the CRAs and PCAs after infusion of hydroxyethyl starch. An improvement of the retrobulbar circulation might be beneficial in the treatment of NAION.


This study was focused on survival analysis of heart failure patients who were admitted to Institute of Cardiology and Allied hospital Faisalabad-Pakistan during April-December (2015). All the patients were aged 40 years or above, having left ventricular systolic dysfunction, belonging to NYHA class III and IV. Cox regression was used to model mortality considering age, ejection fraction, serum creatinine, serum sodium, anemia, platelets, creatinine phosphokinase, blood pressure, gender, diabetes and smoking status as potentially contributing for mortality. Kaplan Meier plot was used to study the general pattern of survival which showed high intensity of mortality in the initial days and then a gradual increase up to the end of study. Martingale residuals were used to assess functional form of variables. Results were validated computing calibration slope and discrimination ability of model via bootstrapping. For graphical prediction of survival probability, a nomogram was constructed. Age, renal dysfunction, blood pressure, ejection fraction and anemia were found as significant risk factors for mortality among heart failure patients. Heart failure is the state in which muscles in the heart wall get fade and enlarge, limiting heart pumping of blood. The ventricles of heart can get inflexible and do not fill properly between beats. With the passage of time heart fails in fulfilling the proper demand of blood in body and as a consequence person starts feeling difficulty in breathing.coronary heart disease, diabetes, high blood pressure and other diseases like HIV, alcohol abuse or cocaine, thyroid disorders, excess of vitamin E in body, radiation or chemotherapy, etc. As stated by WHO [The main reason behind heart failure include d by WHO  Cardiovad by WHO , 33% of d by WHO . Rising Despite of this alarming situation, Pillai and Ganapathi  have repIn addition to relative scarcity of studies focusing on heart failure in this region, the present study has specific importance in the Pakistani context, as diet patterns in Pakistan are different with other the countries of South Asia like India, Bangladesh, Nepal and Sri Lanka.The main objective of this study is to estimate death rates due to heart failure and to investigate its link with some major risk factors by choosing Faisalabad (third most populous city of Pakistan) as study area.Current study is based on 299 patients of heart failure comprising of 105 women and 194 men. All the patients were more than 40 years old, having left ventricular systolic dysfunction and falling in NYHA class III and IV. Follow up time was 4–285 days with an average of 130 days. Disease was diagnosed by cardiac echo report or notes written by physician. Age, serum sodium, serum creatinine, gender, smoking, Blood Pressure (BP), Ejection Fraction (EF), anemia, platelets, Creatinine Phosphokinase (CPK) and diabetes were considered as potential variables explaining mortality caused by CHD. Age, serum sodium and CPK are continuous variables whereas EF, serum creatinine and platelets were taken as categorical variables. EF was divided into three levels  and platelets was also divided into three level on the basis of quartiles. Serum creatinine greater than its normal level (1.5) is an indicator of renal dysfunction. Its effect on mortality was studied as creatinine >1.5 vs ≤1.5. Anemia in patients was assessed by their haematocrit level. Following McClellan et al. [The study was approved by Institutional Review Board of Government College University, Faisalabad-Pakistan and the principles of Helsinki Declaration were followed. Informed consent was taken by the patients from whom the information on required characteristics were collected/accessed.Due to the presence of censored data, survival analysis was used to estimate the survival and mortality rates. Kaplan & Meier  product p explanatory variables X1, X2, ⋯ Xp then the hazard function for ith individual can be defined by Cox model asLet hazard of death depends on For determining the functional form of any particular independent variable following Fitrianto & Jiin  and GillFollowing Pavlou et al.  model vaUp to end of follow-up period, 96 (32%) patients died due to CHD. The results of Cox regression model are presented in Coefficient concerning age indicated that chances of death due to CHD increase with growing age. Hazard of death due to CHD increases by 4% for every additional year of age. EF was another significant factor, hazard rate among patients with EF ≤30 was 67% and 59% higher as compared to the patients with 30<EF≤45 and EF≥45 respectively. In Ejection fraction is an important measurement of how well one’s heart is pumping and is used to help classify heart failure and guide treatment. The EF is also found to be significant correlate of deaths among heart failure patients from Cox regression for present sample. Keeping its importance in view, EF is further analyzed through baseline characteristics  and KaplIn For model validation, calibration slope and ROC curve are developed from 200 bootstrapped samples. Calibration slope was equal to 0.96, which showed that model was not over fitted and predictions made by this model would neither be overestimated nor under estimated.Discrimination ability was checked by ROC curve in Calibration slope and discrimination ability suggested that Cox model is able to predict probability of survival and hazard sufficiently. On the basis of these results, nomogram is presented in For example, an 80 year old non-smoker female diabetic patient with high blood pressure, EF = 40, haematocrit = 35, sodium = 140, creatinine = 5.2, platelets = 300 thousands and CPK = 3000 have points equal to 50+0+8+3+14+56+50+12+40+10+20 = 263 and probability of her survival is 0.60. The Cox model used for constructing this nomogram was fitted on original values of variables.The statistical analysis identified age, EF, creatinine, sodium, anemia and BP as the significant variables affecting the likelihood of mortality among heart failure patients. Most of studies –17 suppoThe findings that seem surprising are non-significance of smoking and diabetes. However, similar results concerning diabetes and smoking have been reported in other studies –25 as wePerformance of model was checked using calibration slope and ROC curve. Both concluded in adequacy of model for prediction. ROC curves were also used to discuss the goodness of model with respect to time. Nomogram was used to find the probability of survival by graphical method. It was observed that fall of survival probability was almost same for Kaplan Meier plot and nomogram.It can be concluded that growing age, renal dysfunction , high BP , higher level of anaemia and lower values of ejection fraction (EF) are the key factors contributing towards increased risk of mortality among heart failure patients. Increased level of serum sodium can reduce the odds of death. No significant differences were found due to smoking status, diabetes and gender of patients.S1 Data(CSV)Click here for additional data file.


Twenty‐four hour urine samples, blood glucose, creatinine, and cystatin C were obtained from non‐Hispanic white sibships in Rochester, MN . Diet was assessed by a food frequency questionnaire. The impact of blood glucose, demographics and dietary elements on Ucit excretion, U‐pH, and NAA were evaluated in bivariate and multivariable models and interaction models that included age, sex, and weight. NAA significantly associated with Ucit and U‐pH. In multivariate models Ucit increased with age, weight, CeGFRys, and blood glucose, but decreased with loop diuretic and thiazide use. U‐pH decreased with serum creatinine, blood glucose, and dietary protein but increased with dietary potassium. NAA was higher in males and increased with age, weight, CeGFRys and dietary potassium. Significant interactions were observed for Ucit excretion with age and blood glucose, weight and CeGFRys, and sex and thiazide use. Blood glucose had a significant and independent effect on U‐pH and also Ucit. This study provides the first evidence that blood glucose could influence urinary stone risk independent of urinary pH, potentially providing new insight into the association of obesity and urinary stone disease.Urinary citrate (Ucit) protects against urinary stone formation. Acid base status and diet influence Ucit. However, the effect of demographics, diet, and glucose metabolism on Ucit excretion, urinary  Kidney stones are common, affecting up to 10% of people during their lifetime .The multi‐phase Genetic Epidemiology Network of Arteriopathy (GENOA), a member of the Family Blood Pressure Program (FBPP), recruited non‐Hispanic white hypertensive sibships from Rochester, Minnesota for linkage and association studies to investigate the genetic underpinnings of hypertension in Phase I (1996–2001)    while cystatin C was measured using an immunoturbidometric assay  that was traceable to an international reference material. Glomerular filtration rate (GFR) was independently estimated using cystatin C  , diuretic thiazide use (yes/no), and dietary animal protein, sodium, calcium, fructose, oxalate, total protein, and sucrose intakes. Net alkali absorption was calculated using the Oh method: (Urine(Na + K  +  Ca + Mg)‐(Cl + 1.8P)) were forced into each model.A randomly selected, independent subset of the GENOA cohort  was used for stepwise linear regression to determine the variables that were associated with urinary citrate, pH and net alkali absorption. Variables available for selection included: weight, body mass index (BMI), smoking status (current‐ or never smoker), diabetes status (yes/no), recent fasting blood glucose level (within 1 year of the urine collection), systolic blood pressure (SBP), diastolic blood pressure (DBP), eGFR1.8P))Oh . The entTo evaluate and visualize the relationship between citrate and net alkali absorption Fig. , pH and n = 446) to assess significant predictors of the urinary measures, accounting for the sibship structure in GENOA. Interaction models were also conducted to assess age, sex, and weight (if weight was included in the model selection as a predictor) interactions with the variables included in the models. Interactions were considered significant at an alpha level of 0.05. Sensitivity analyses were performed by running the final multivariable models in the subset of participants with no history of kidney stones to assess direction and significance of the final variables.After variable selection, LMM was performed on the GENOA subset sample with complete data on all selected variables (cys x weight (4B); and sex x thiazide diuretic use (4C) interactions on urinary citrate excretion, as well as the interaction between loop diuretic use and weight on net alkali absorption (4D). Multivariable regression models that included the stepwise selection variables were run for each interaction. To calculate predicted urinary outcome, the beta estimates for continuous predictor variables were multiplied by the mean value for the respective variable from the sample, and for dichotomous variables, the reference group was used where appropriate . Three values for the continuous variables of interest . Urine pH adjusted for age, sex, serum creatinine dietary potassium intake, blood glucose, loop diuretic use, and dietary protein intake also positively associated with adjusted net gastrointestinal alkali absorption . However, adjusted citrate and adjusted urine pH were only weakly and not significantly associated .Urinary citrate, adjusted for age, sex, serum creatinine, dietary potassium intake, weight, blood glucose, eGFRCys, and blood glucose, and negatively associated with serum creatinine and loop diuretic use. Urinary pH decreased with increasing serum creatinine and blood glucose, and was also decreased for those taking loop diuretics.In the bivariate analysis Table  there waCys, and blood glucose, and decreased with loop diuretic and thiazide use. Urine pH decreased with serum creatinine, blood glucose and dietary protein and increased with dietary potassium. Net alkali absorption was higher in males and increased with age, weight, eGFRCys and dietary potassium.In the multivariable model Table  urinary β = −0.20, P = 0.01), weight and eGFRCys , and sex and thiazide use . One significant interaction for net alkali absorption with weight and loop diuretic use was also observed .Three significant interactions were observed Fig. A–C for uIn this study, we assessed the effects of demographics, metabolic parameters, and diet on urinary citrate, pH, and net alkali absorption. As previously described, net gastrointestinal alkali absorption influenced urinary citrate , but not stone formers (n = 132) . However, only 14 individuals were >60 years old , likely due to a low number of participants (n = 21), the direction of effect was the same as that in the current study. Similar findings were also reported in a study of 252 stone formers , this relationship provides important insights, since the relation between age and urinary citrate interacted significantly with blood glucose , Nurses’ Health Studies (NHS I and II) and found diabetes to be associated with higher urinary citrate excretion in men and younger women (Mandel et al. Cys (Fig. /− animals demonstrated no significant alteration in serum citrate levels, suggesting that metabolic citrate production is more important than citrate absorption via the gut (Ho et al. Higher body weight was also associated with greater urinary citrate excretion Table . Powell Cys Fig. B. This cA lower urinary pH has also been observed in those with a higher BMI (Maalouf et al. We found thiazide use associated with decreased urinary citrate, as previously shown (Mandel et al. Several interesting associations with urinary citrate excretion were observed, some of which paralleled effects on urine pH and others which did not. Urine pH decreased with protein intake which can be explained by the increased acid load from protein. Dietary potassium increased urine pH, perhaps due to relatively higher ingestion of fruits and vegetables (Pearle et al. Our study has limitations. Participants were of European descent and of relatively older age. Eisner and colleagues found Asian/Pacific islander stone formers to have less urinary citrate excretion than Whites (Eisner et al. In conclusion, our study points toward the ambient blood glucose concentration as having a measurable unique influence on urinary citrate excretion and pH. While age and weight also associated with urinary citrate excretion, the effect of age interacted with blood glucose levels, rather than reduced kidney function. A deeper understanding of the relation between blood glucose and urinary citrate excretion could increase our understanding of the interrelationship between obesity, insulin resistance, urinary citrate, and kidney stone risk.The authors declare that they have no conflict of interest.


Patients with compromised peripheral perfusion, high doses of vasopressor drugs or peripheral edema were excluded. Differences in systolic, diastolic and mean BP of 5  mmHg (accuracy and precision) between both methods were considered acceptable. Additionally, the magnitude of beat-to-beat fluctuations in systolic BP of both methods was compared. In AF, the differences between noninvasive and invasive BP were −4 (SD 12), +1 (SD 7) and 0 (SD 8) mmHg for systolic, diastolic and mean BP respectively. Absolute differences in beat-to-beat BP fluctuations were 1.5 (IQR 0.8–3.8) mmHg. Accuracy of VCM in AF was similar to sinus rhythm. In conclusion, in patients with AF, accurate and precise measurement of non-invasive beat-to-beat BP measurement using the VCM is possible, the one exception being the precision of systolic BP. Beat-to-beat variability can be accurately reproduced.International guidelines highlight the importance of blood pressure (BP) in patients with atrial fibrillation (AF). However, BP measurement in AF is complicated by beat-to-beat fluctuation. Automated BP measurement devices are not validated for patients with AF and no consensus exists on how to measure BP in AF manually. Beat-to-beat BP measurement using the volume-clamp method (VCM) could represent a non-invasive method to accurately assess BP, but has not been validated in AF. 31 admitted patients with sustained AF and 10 control patients with sinus rhythm underwent simultaneous intra-arterial and non-invasive BP measurement using a VCM monitor (NexfinThe online version of this article (doi:10.1007/s10877-017-0044-9) contains supplementary material, which is available to authorized users. Atrial fibrillation (AF) is the most common arrhythmia with an incidence of 60 per 100,000 person-years in women and 78 per 100,000 person-years in men. The prevalence increases with age from 0.1% among adults younger than 55 years to 9.0% in persons aged 80 years or older . ReductiGlobally, elevated blood pressure (BP) is the leading risk factor for death and disability-adjusted life-years lost , but is Given the importance of BP in patients with AF, the subject of accurate measurement receives surprisingly little attention in the international literature. Current AF guidelines do not provide clear or uniform recommendations on how to measure BP in AF , 10. No Taken together, BP monitoring in patients with AF remains problematic. Intra-arterial measurements reliably follow rapid changes in BP, even on a beat-to-beat basis, and are the preferred reference method for BP measurement in AF. However, this is obviously unfeasible in daily clinical practice given the invasive nature of the procedure. Reliable non-invasive beat-to-beat BP measurement would be ideal to serve as either a routine clinical method, or as a reference method for comparison of other non-invasive methods, such as manual or oscillometric measurements.The volume-clamp method (VCM) is a non-invasive technique that has been validated in several different populations and conditions  –20. ArteFor this study, the need to obtain informed consent of the participating patients was waived by the Medical Ethical Committee. Patients with AF who had an intra-arterial catheter in the radial artery for BP monitoring on the intensive care unit, medium care unit or coronary care unit were eligible for this study. Patients with reduced peripheral perfusion as assessed by clinical features , high-dose vasopressor drugs (>0.24 µg/kg/min norepinephrine) and/or moderate or more severe peripheral edema  were excA finger cuff was applied to the mid-phalanx of the second, middle or fourth finger ipsilateral to the arm with the intra-arterial catheter. The “finger side” of the heart reference system (HRS) was fixed next to the finger on which the cuff was applied. The “heart side” of the HRS was fixed at right atrial level on the patient’s gown. The level of the right atrium was assumed to be located at the fourth intercostal space at the mid-anterior–posterior diameter of the chest wall. At the same height, the pressure transducer was positioned on a pole next to the patient’s bed, preventing errors in BP due to difference in height , 22.All patients included had an intra-arterial line for BP monitoring as part of usual care. The arterial line was placed in the radial artery (left or right) with a 20 gauge cannula. The catheter was connected to a monitor of Philips IntelliVue MX800 . The catheter–manometer system was flushed with 0.9% saline to minimize air in the line from catheter to monitor before measurements would be used in the comparison with VCM pressures.Continuous finger arterial and intra-arterial pressures were measured simultaneously. In the first minutes of measurement the positions of the finger cuff and pressure transducer were checked for possible hydrostatic level errors and, if necessary, readjusted. Subsequently, BP was measured for 15 min. During the BP measurement, no therapeutic changes were made. The non-invasive and invasive arterial blood pressure curves of all patients were A/D converted at 200 Hz and stored for off-line analysis [The main study parameters were the differences in systolic, diastolic and mean BP between VCM and intra-arterial measurements. Additionally, beat-to-beat variability was quantified.®) occurred more often than once every 30 heartbeats. The VCM device automatically translates BP to corresponding brachial artery levels. Since systolic BP is physiologically amplified between the brachial and radial artery, comparing VCM directly to radial intra-arterial pressures would lead to underestimation. Therefore, the intra-arterial radial artery pressure was corrected for (age-adjusted) BP amplification to reconstruct brachial artery pressures .Data of all patients were analyzed by comparing each single-beat BP curve of the VCM with the corresponding curve obtained from intra-arterial measurement. Data were discarded if the intra-arterial BP signal was visually damped or when the automatic calibration of the Nexfin  were selected. Data analyses  was performed using linear regression analysis, intra-class correlation and Bland Altman plotting for systolic, diastolic and mean BP. A mean difference of 5 (SD 8) mmHg (accuracy and precision) was considered acceptable as proposed by the Association for the Advancement of Medical Instrumentation American National Standard ANSI/AAMI/ISO 2009 guidelines . HoweverData analyses of all single-beat BP measurements  were similarly performed for each patient separately. The mean of the individual SDs was calculated as a measure of individual consistency (“Within-subject precision”) .The statistical software package SPSS was used for statistical analyses .We included 31 patients with AF and 10 with SR between June 2013 and January 2014. Clinical characteristics are displayed in Table Accuracy data are listed in Table Bland Altman plots and analyses for systolic, diastolic and mean BP, as well as for beat-to-beat difference are displayed in Fig. Data analyses of data on patient level are listed in supplemental Table 1. Within-subject precision of systolic BP was accurate with a mean SD of 5.1 (SD 2.6). As expected, within-subject precision for systolic BP was better than group level precision (SD 12).Notably, in one-third of the patients (10/31 patients) with AF and SR  there was a substantial difference of >10 mmHg between VCM and intra-arterial systolic BP measurements. In these 13 patients, the VCM was not accurate and precise compared to the intra-arterial BP. The most plausible explanation in all patients with AF and SR can be found in their baseline characteristics. Most patients used low-dose noradrenaline and/or had somewhat pale and cold hands or minor edema, but none severe enough for exclusion . A regression model between the bias of systolic BP measurements  and low-dose noradrenaline, minor edema, and minor paleness and cold hands, showed no significant relation between the bias and low-dose noradrenaline or pale cold hands , however, there was a significant relation between bias and minor edema  with an estimated 7.7 mmHg lower measurement with VCM compared to intra-arterial BP measurements. Absolute beat-to-beat differences of systolic BP were accurate (median absolute beat-to-beat difference <4.0 mmHg) in virtually all patients with AF except for patient 5.Analyses of data that are first aggregated to individual patient level  yield virtually equal results compared to collective data analyses .The most important finding in this study is that the non-invasive VCM method is accurate in measuring beat-to-beat BP in patients with AF. The VCM method could thus provide an easy, reliable and accessible method for clinical use, as well as for epidemiological studies of BP in AF, and validation studies for other BP monitoring methods and systems in AF.Mean values of systolic BP measurements were accurate with the VCM method (<5 mmHg), but the standard deviation for systolic BP (12 mmHg) is above the limit proposed by the Association for the Advancement of Medical Instrumentation American National Standard ANSI/AAMI/ISO 2009 guidelines  . For diaHowever, whether this standard benchmark for validation is appropriate for AF is questionable, since a “zero-zone method”  is propoOur results indicate that the VCM method is appropriate for the validation of other BP measurements methods and devices in patients with AF. Although VCM is currently recommended for non-invasive hemodynamic monitoring in some critical ill patients, these studies did not investigate the validity in patients with AF solely . As mentSome limitations of this study should be considered. First, this is a validation study in patients that were hospitalized and either post-operative or critically ill patients. However, since intra-arterial measurements in stable outpatients are ethically problematic, this type of study may simply be unfeasible in outpatients.In addition, BP measurement with VCM was inaccurate in one-third of all patients. However, results where similar for patient with SR. In most cases where VCM differed substantially from intra-arterial measurement, vasopressors and/or peripheral edema provided a plausible explanation for this. Also, the small within-subject variability indicates that the differences remain stable. It has been described previously that in patients with critical illness the signal of the systolic BP is damped . It thusFinally, the validation study required adjustment of radial intra-arterial BP values to corresponding brachial levels, which were the basis of the original VCM validation studies. Intra-arterial measurements of BP in the brachial artery could be more accurate as a reference method.In conclusion, VCM can measure BP, including its beat-to-beat fluctuations, accurately in patients with AF. This result enables a range of future studies addressing both measurement techniques as well as the clinical importance of BP (fluctuations) in patients with AF.Below is the link to the electronic supplementary material.Supplementary material 1 (DOCX 28 KB)Supplementary material 2 (DOCX 19 KB)Supplementary material 3 (DOCX 18 KB)Supplementary material 4 (DOCX 17 KB)