Colic, defined as pain originating from the abdomen, is a common condition in horses. Most of the cases resolve spontaneously or after medical treatment, but a few require surgical treatment. Surgical treatment of colic in horses is resource-demanding and expensive, and information on prognosis is therefore important for both owners and surgeons. In the present study, surgical cases in two equine hospitals in Norway between 2005 and 2011 were reviewed. The aim of the study was to describe associations between prognostic indicators, diagnoses and short term survival by use of random effects logistic regression.P-value <0.20 and were assessed in multivariable analyses. Respiration rate, rectal temperature and lactate in blood also had univariable P <0.20, but were left out from multivariable analyses due to too high levels of missing values. A random effect of primary surgeon was included and breed, sex and age were tested in multivariable analyses as possible confounders; and hospital was included to control for hospital routine differences. In the final multivariable model the variables mucosal membrane appearance, affected gastrointestinal segment and surgeon board-certification significantly influenced survival. The random surgeon effect was not significant.In the present study, 162 out of 297 (54.5%) surgeries resulted in the horse being discharged from the hospital. Excluding cases euthanized during surgery, the overall short-term survival was 74.0% (162 out of 219 surgeries). Seventy-eight (26.3%) of the horses were euthanized during surgery, due to grave or poor prognosis. In univariable analyses, duration of colic signs, heart rate, capillary refill time, mucosal membrane appearance, intestinal sounds, affected gastrointestinal segment, hematocrit, intestinal resection, hospital and surgeon board-certification had The present study showed that prognostic parameters and diagnoses of surgical treatment of horses with colic in Norway are in accordance with reports from other parts of the world. The significant effect of board-certification of surgeon is not reported in previous studies. The general short-term survival rate was somewhat lower than reported in other studies, partly due to more horses being euthanized intraoperatively in the present study. This might be because of economical or animal welfare reasons. Colic, defined as pain originating from the abdomen, is a common condition in horses. An incidence of 4.2-10.6 colic cases/100 horse-years is reported from the United States and Great Britain. A Swediet al.[There are a number of studies published on the survival of horses undergoing colic surgery, both for specific conditions and overall survival,12-18. Het al., the stuet al., affecteet al. and surget al. are all et al.-18. SystCase records of all horses undergoing laparotomy due to abdominal pain in two equine hospitals in Norway between 2005 and 2011 were reviewed, altogether 317 horses. All horses were admitted to the hospitals due to a perceived serious colic condition. Hospital 1 accepted only cases referred by a veterinarian in the period reviewed, while Hospital 2 also accepted horses without a veterinary examination beforehand. Of these, seven horses had lesions in organ systems other than the gastrointestinal tract diagnosed prior to surgery  and were thus excluded from the study. Four horses were euthanized in the recovery stall due to fractures (n = 3) or femoral nerve paralysis (n = 1), and were also excluded from the study. Nine horses had a second laparotomy performed due to persisting colic and were omitted as well. Altogether 297 horses were included in the study population. The breed and age distribution of the included cases are presented in Table The results of the last physical examination prior to surgery were defined as preoperative clinical variables. Thirty horses also had the total solids, referring to proteins and lipids, of abdominal fluid measured. Lactate measurements were available at Hospital 1 for the whole period, and at hospital 2 from 2010 and onwards. At Hospital 1 an ABL-800 FLEX®  was used for the lactate analysis, and at Hospital 2 a handheld Accutrend®  was used. Total solids in plasma and abdominal fluid were measured by a refractometer . As lactate had almost 50% missing values and was measured with two different methods, this variable was left out from the analyses. An overview of the variables with total number of observations and number and percentage missing observations of each variable is presented in Table All laparotomies were performed under general anesthesia in dorsal recumbency. Enterotomy and resection of bowel were classified as performed/not performed. Surgeons worked in a team of two for the majority of surgeries. All surgeons serving as primary surgeons had several years of experience with laparotomies in horses. Eleven different surgeons were serving as primary surgeon in the period reviewed, with 30 different surgeons serving as assistant surgeons. Two surgeons were board-certified by the American College of Veterinary Surgeons (ACVS) and one by the European College of Veterinary Surgeons (ECVS), all three working at Hospital 1. Twenty six different anesthetists were involved. Diagnoses were based on surgical exploration, with the exception of horses euthanized during surgery where a final diagnosis was made at post mortem examination.Both the participating hospitals are located in Oslo, and mainly serve the equine population in the south-eastern part of Norway, although cases are referred from all over the country. The surgical team performing colic surgeries at both hospitals consists of two surgeons and a nurse assisting. At Hospital 1 a veterinarian or a nurse specialized in anesthesia are responsible for the anesthesia, while at Hospital 2 a nurse or intern is handling anesthesia.Pre-operative treatment at both hospitals was constantly adjusted according to recent literature in the period reviewed, but in general consisted of penicillin 22.000 IE/kg body weight (bwt) intravenously (iv.), gentamycin 6.6 mg/kg bwt iv., flunixin meglumine 1.1 mg/kg bwt iv., fluid therapy according to need and further analgetics if needed (α-agonists and butorphanol iv.). Postoperatively, antibiotics (procaine penicillin 22.000 IE/bwt intramuscularly (im.) twice a day and gentamycin 6.6 mg/kg bwt iv. once a day) were continued for 5–10 days and flunixin meglumine for at least 3 days, longer if needed. Sucralfate  three times a day) were given as prophylaxis against gastric ulcers until the horse was back on normal feed ration, and omeprazole (4 mg/kg bwt po. once a day) if gastric ulcers were confirmed. In cases involving resection of intestine, strangulated small intestine or ileus was treated with lidocaine as a bolus of 1.3 mg/kg bwt iv. followed by constant rate intravenous infusion of 0.05 mg/kg bwt/min iv. for 24–48 hours postoperatively. Clinical status was taken every third hour 24–48 hours postoperatively, or longer if needed. Hematocrit, total solids in blood and blood gas analysis were done 1–2 times a day, or more often if indicated. A nasogastric tube passed as needed if ileus or discomfort occurred.P-value ≤ 0.20 from the likelihood ratio test (LRT) and the multiple Wald test were selected for further multivariable analysis, provided that there was no colinearity between them. When colinearity was detected, the variable with the strongest univariable P-value and fewest missing data was selected for further analysis.The main outcome variable was short-term survival (STS) defined as a horse being discharged from the hospital, or not. The outcome variable was thus a dichotomous variable and logistic regression was applied. Variables  with more than 25% missing observations were omitted from the analyses. The variables were first tested unconditionally with univariable logistic regression. Continuous variables were evaluated for linearity by lowess curves and by adding the quadratic term of the variable. Continuous variables showing a non-linear relationship with the outcome variable were categorized into biologically plausible categories. Thus, the variables duration of signs, heart rate, capillary refill time, hematocrit, anesthesia duration and hospitalization time displayed a non-linear relationship with the outcome and were categorized. Heart rate was classified as normal or elevated (>44 beats per minute), capillary refill time classified as less than 2 seconds, between 2 and 3 seconds, and more that 3 seconds, and hematocrit was classified as normal (0.32-0.42), low (<0.32) or increased (>0.42). The variable duration of signs was grouped into four categories based on percentiles. Anesthesia duration was classified as less than 120 min, more than 120 min or as euthanized intraoperative. Variables were then screened for colinearity by pair wise correlations for continuous variables and by Goodman and Kruskal’s gamma for dichotomous and ordinal variables,23. AssoP-value. Variables were retained in the model when the P-value of the LRT and multiple Wald test was < 0.05. Potential confounding and intervening variables were evaluated based on both a tentative causal diagram and changes in effects during model building. All possible two-way interactions between statistically significant variables in the model were tested by adding interaction terms to the model. Due to the large number of interactions tested, a more restrictive P-value was applied. Interaction terms were retained if the P-value of the LRT was < 0.01. The LRT was used to evaluate the significance of the random surgeon effect in the models with and without random surgeon effect, but containing the same fixed effects. The LRT was considered significant at P = 0.05 and one-sided test.There were 11 primary surgeons with an average of 26 records per surgeon, and a random effect of surgeon was used in the analyses. As only Hospital 1 had board-certified surgeons available in the revised period, the statistical analysis of this parameter was also done with a reduced data set, containing only surgeries performed in Hospital 1. A multivariable random effects logistic regression model with outcome survival yes/no was constructed by manual forward selection by offering variables selected from the univariable analyses one-at-a-time to the model by ascending univariable The multiple Wald test and LRT were used to evaluate differences between categories of categorical predictors. The Stata command lincom was used to conduct contrasts among each category of categorical predictors.2surgeon) was estimated. The intraclass correlation coefficient (ICC) calculated by the latent variable approach, assuming that horse level variance (σ2) is the constant π2/3 was calculated using.From the final multivariable random effects logistic regression model the between surgeon variance  was used for all analyses.Out of the 297 horses there were 132 (44.4%) geldings, 111 (37.4%) females and 53 (17.8%) intact males. Sex was not recorded in one case. Median age was 7 years.A total of 179 surgeries were performed at Hospital 1 and 118 surgeries were performed at Hospital 2. Of the 316 surgeries performed, 162 (54.5%) resulted in the horse being discharged from the hospital. Excluding the 78 cases euthanized during surgery, the overall short-term survival was 74.0% (162 of 219 surgeries). The occurrence of each diagnosis and the corresponding short-term survival are presented in Table P-values for variables with less than 25% missing values, and P-value below 0.2 from the univariable analyses are presented in Table Descriptive statistics and results with odds ratio (OR) and Seventy-eight (26.3%) of the horses were euthanized due to grave prognosis because of rupture/perforation of intestine (n = 10) or perceived poorer prognosis due to non-viable intestine (n = 68). Of the 219 cases brought into recovery, 97 (44.3%) had an enterotomy performed and 21 (9.6%) had intestinal resection and anastomosis performed.P-value ≤ 0.20 and thus were eligible for inclusion in the multivariable analyses were: duration of colic signs, heart rate, mucus membrane appearance, capillary refill time (CRT), hematocrit, intestinal sounds, affected gastrointestinal segment, intestinal resection, duration of hospitalization, primary surgeon, and whether the primary surgeon was a board-certified specialist or not. Breed, sex and age were included as potential confounders, and hospital was included as a fixed effect to control for hospital routine differences.The variables that had univariable P-values, and 95% confidence intervals from the final multivariable model are presented in Table Results with OR, P = 0.225).When building the multivariable model, the random surgeon effect was moderate at 6%, but significant  until adding the variable board-certified surgeon or the variable hospital. Then the random surgeon effect became negligible at 0.5% and non-significant  of the 297 horses that underwent surgery were euthanized in the postoperative period. The reasons for euthanization were not documented for each case, but in general ileus, persisting colic signs, laminitis and animal welfare concerns were common reasons for euthanasia. Economical limitations are also involved, as prolonged intensive care rapidly becomes expensive.et al.[STS for large colon volvulus in the present study was low, with 14 out of 37 cases discharged (STS 37.5%), compared to the STS of 70.7% reported by Suthers et al.. Also, iet al.. These aet al.. Most liet al.[Impaction of the cecum had a low STS in the present study, with 2 out of 12 cases discharged (STS 16.7%), which is low compared to the 65% reported by Smith et al.. One stuet al.. Cecum iet al.; this alThe distribution of different lesions requiring surgical treatment in the present study is similar to the study by Mair and Smith, althougThe cardiovascular parameters were significantly associated with survival in the present study. This is in accordance with most studies published on prognostic factors in treatment of both surgical and medical equine colic,17,24,25The rectal examination findings were not found to have a significant effect on survival in these surgical colic cases. Findings on rectal examination is one of the important criteria in the decision for choosing surgical treatment, and is thus biased towards abnormal findings.Affected intestinal segment did show significantly influence on survival. Lesions in the large colon doubled the odds of survival compared to small intestine. This is in accordance with other studies,10,17, aAlthough there were reduced odds for survival when the duration of anesthesia exceeded 120 minutes, this was however not statistically significant to survival in the univariable analysis. This is most likely a reflection of the fact that severe conditions require more complicated procedures and thus a longer period of anesthesia, without the prolonged anesthesia itself being cause of increased mortality.The random effect of primary surgeon, and the fixed effects of surgeon specialist and hospital all were significant to the outcome in univariable analysis. In the multivariable model, however, the effect of hospital and the random effects primary surgeon were not significant when surgeon specialist was added as a fixed effect. Although all surgeons serving as primary surgeons in this study had long experience of abdominal surgery, the training and requirements to become a board-certified surgeon are likely to improve the techniques and skills of the surgeon, and thus increase survival. Likewise, differences in intraoperative procedures, other than the strictly surgical technique, and post-operative treatment could be of influence, as this most often is the responsibility of the primary surgeon. Only Hospital 1 had board-certified surgeons available during the period investigated, and the effect was significant also when including only cases from this hospital.Missing data are common in observational studies, and in the present study there were varying degrees of missing observations for some variables, some as high as 50%. This might be related to the fact that most colic cases are acute and sometimes dramatic, and record keeping might not be given a high level of priority. High numbers of missing data can also be a reflection of the attending clinicians’ attitudes towards the importance of different parameters. For instance, parameters such as heart rate, mucosal membranes, hematocrit and intestinal sounds, long established as good prognostics in equine colic patients, usually were recorded. More surprising was that 47.8% of the cases are missing information on reflux of gastric content, also a recognized prognostic parameter. This might be because results retrieved during clinical examination sometimes are not recorded if not providing decisive information. Statistical programs for building regression models work on the basis of complete sets of observations, and even a relatively low overall percentage of missing values can result in a substantial reduction in statistical power and hence fail to detect associations that are in fact present. Although the present study identified a number of significant variables related to STS of surgically treated colic patients, more complete records would have provided a better basis for multivariable analyses. Missing data can if not occurring at random, introduce bias and the analysis might result in associations that are severely biased and not valid. For instance, the blood lactate level in blood is often recognized as a significant variable regarding STS in surgical treatment of colic, but had almost 50% missing values in the present study. It might be that the patients missing the blood lactate parameters were unequally distributed across the outcome variable and other predictor variables than the patients where the blood lactate were recorded. Thus, including this variable in a multivariable model might bias the results of the model. Even if blood lactate was not included in the present study, other studies have identified colinearity with other circulatory variables such as heart rate, mucosal membrane appearance and hematocrit.Retrospective studies on the survival and prognosis after surgical treatment of equine colic are regularly published. Many ofThe present findings regarding surgical treatment of equine colic patients in Norway are in many aspects similar to those reported from other parts of the world, although the survival rate is lower than in similar studies. In addition, the present study showed an increased survival if the surgeon was board-certified. Studies on long-term survival have become available in recent years, and would be a logic next step for further research, although long-term follow up often is practically challenging.The authors declare that they have no competing interests.BW collected the data from Hospital 1, participated in the design of the study and drafted the manuscript. CI helped draft the manuscript and participated in the design of the study. RD collected the data from Hospital 2 and participated in the design of the study. RK performed the statistical analysis and helped draft the manuscript. All authors read and approved the final manuscript.


Risk factors have been identified for increased probability of developing renal toxicity after PRRT, including hypertension, diabetes and age. We investigated the renal function over time, the incidence of nephrotoxicity and associated risk factors in patients treated with PRRT with -Octreotate (177Lu-Octreotate). Also, radiation dose to the kidneys was evaluated and compared with the accepted dose limits in external beam radiotherapy and PRRT with 90Y-radiolabelled somatostatin analogues.After peptide receptor radionuclide therapy (PRRT), renal toxicity may occur, particular in PRRT with The annual decrease in creatinine clearance (CLR) was determined in 209 Dutch patients and the incidence of grade 3 or 4 renal toxicity (according to CTCAE v4.03) was evaluated in 323 patients. Risk factors were analysed using a nonlinear mixed effects regression model. Also, radiation doses to the kidneys were calculated and their association with high annual decrease in renal function were analysed.Of the 323 patients, 3 (1 %) developed (subacute) renal toxicity grade 2 . No subacute grade 3 or 4 nephrotoxicity was observed. The estimated average baseline CLR (± SD) was 108 ± 5 ml/min and the estimated average annual decrease in CLR (± SD) was 3.4 ± 0.4 %. None of the risk factors  at baseline had a significant effect on renal function over time. The mean absorbed kidney dose in 228 patients was 20.1 ± 4.9 Gy.177Lu-octreotate was low. No (sub)acute grade 3 or 4 renal toxicity occurred and none of the patients had an annual decrease in renal function of >20 %. No risk factors for renal toxicity could be identified. Our data support the idea that the radiation dose threshold, adopted from external beam radiotherapy and PRRT with 90Y-labelled somatostatin analogues, does not seem valid for PRRT with 177Lu-octreotate.Nephrotoxicity in patients treated with The online version of this article (doi:10.1007/s00259-016-3382-9) contains supplementary material, which is available to authorized users. Although the side effects of this therapy are mild, renal toxicity has been observed, particularly in PRRT with 90Y-DOTATOC with an average annual decrease in creatinine clearance (CLR) of 7 % in contrast to 3 % for 177Lu-Octreotate Octreotide scintigraphy  with accumulation in the tumour at least as high as in normal liver tissue; no prior treatment with PRRT; baseline serum haemoglobin (Hb) ≥6 mmol/l; white blood cells ≥2 109/l; platelets ≥75 109/l; Karnofsky performance status ≥50; serum creatinine ≤150 μmol/l; and 24-h CLR ≥40 ml/min. Of the 615 patients, 323 Dutch patients were selected for this long-term evaluation, because loss to follow-up is limited in these patients.A total of 615 patients, who were treated from January 2000 to December 2007 were studied. Inclusion criteria for the study were: patients with somatostatin positive tumours and baseline tumour uptake on Octreotate was obtained from BioSynthema . 177LuCl3 was supplied by IDB-Holland  and 177Lu-Octreotate was locally prepared [[DOTAprepared .177Lu-Octreotate. Infusion of amino acids  was started 30 min before administration of the radiopharmaceutical and lasted for 4 h. The radiopharmaceutical was coadministered for 30 min using a second pump system. The interval between treatments was 6 – 16 weeks. The intended cumulative activity was 29.6 GBq (800 mCi). Median cumulative activity was 29.6 GBq (range 7.4 – 29.6 GBq) and the median number of therapy cycles was four (range one to eight). However, the total administered activity was lowered if the calculated kidney dose was higher than 23 Gy. Other reasons for dose reduction or cessation of further therapy were recurrent grade 3 or 4 haematological toxicity and persistently low blood cell counts.Granisetron 3 mg or ondansetron 8 mg was injected intravenously 30 min before infusion of Haematology, liver and renal function tests were performed during the 6 weeks before the first therapy, 4 and 6 weeks after each therapy, and at follow-up visits. Acute and long-term renal toxicity assessment was done according to Common Terminology Criteria for Adverse Events (CTCAE v4.0) .Hypertension was defined as the use of antihypertensive drugs . Diabetes mellitus was defined as an HbA1c of ≥6.0 % and/or the use of antidiabetic medication (insulin and insulin sensitizers). CLR in millilitres per minute was used as an estimate of glomerular filtration rate (GFR). Four serum-based methods were used to determine baseline 24-h urine CLR, and the results compared see . The CocSPSS  and R  software was used for statistical analysis. The Shapiro-Wilk test was used to assess the normality of the response. The primary outcome was CLR predicted by a nonlinear mixed effects regression model with independent factors . Various functional model forms  were fitted to the CLR data see . The non1 and factor2 are constants, given specific values of the covariates included in the mixed model. The combined term where 177Lu-Octreotate. Extensive information regarding the dosimetric method is provide in an earlier paper [S-factors for 177Lu derived from the Radiation Dose Assessment Resource (RADAR) website [Uptake of radioactivity in the kidneys was determined by planar imaging at 1, 3 – 4 and 7 days after administration of er paper . Dosimet website , 15. The website :\documenDkidneys) is calculated as the product of the number of decays in a source organ (Ãs) and the S-value, which expresses the dose rate per radioactivity for a source (rs) to target (rt) combination. With moderately weak β-particle-emitting radionuclides such as 177Lu, only the self-dose needs to be considered (rs = rt). The radioactivity uptake and clearance kinetics of 177Lu-Octreotate As(t) in the kidneys is needed for calculation of the radiation dose to the kidneys, together with the S-value for the kidney self-dose. The 177Lu S-values were taken from the RADAR website [S-value is 0.289 mGy/MBq.h and for a adult female kidneys (with a mass of 275 g) the S-value is 0.314 mGy/MBq.h. In a subgroup of patients, the kidney volume was determined based on baseline CT images, since complete kidney imaging was not always available. A correction factor and adjusted dose were calculated in these patients, using OsiriX 5.9 . A polygonal region of interest was (semi)automatically drawn on each CT slice and the slices were summed for calculation of the total kidney volume.The dose to the target organ . Patient characteristics are summarized in Table Of the 323 patients, 14 (4 %) had a (sub)acute toxicity grade 1 (creatinine increase >26.5 µmol/l). Three patients (1 %) developed (subacute) toxicity grade 2 . These were judged not related to therapy: one patient had received prolonged antibiotics due to an infection and developed temporary renal insufficiency, one patient was dehydrated because of diarrhoea, and one patient showed progression of disease with hypoalbuminaemia and forward heart failure resulting in death 2 weeks after the first treatment. No grade 3 or 4 (sub)acute nephrotoxicity was observed.Follow-up data for 1, 2 and 3 years after the last therapy were available in 209, 155 and 98 patients, respectively. Grade 3 kidney toxicity was observed in 5 out of the 323 patients during this follow-up. Toxicity was not related to PRRT since all five patients had a baseline CLR of <60 ml/min (i.e. grade 2), making them more prone to more severe renal function impairment. However, the annual decrease in CLR was <12 %. The distribution of CLR at baseline and during follow-up  is shown in Fig. Follow-up of more than 1 year was available in 209 of the 323 patients. One patient with an incomplete set of risk factors was excluded; thus the analysis included 208 patients. The estimated average annual decrease in CLR (± SD) was 3.4 ± 0.4 %, and the estimated average baseline CLR (p < 0.0001). With all other factors held constant, the estimated average baseline CLR showed a significant decrease in patients older than 70 years or with baseline CTCAE grade 2. None of the risk factors considered for inclusion in the model  had a significant effect on the estimated rate of change in CLR over time, and were thus not included in the final model.Age and baseline CTCAE had significant effects on the baseline CLR  in 407 patients. The mean radiation dose to the kidneys was 19.3 ± 5.0 Gy Fig. a. The me Gy Fig. b. The me Gy Fig. c, and 11177Lu-Octreotate, the average annual decrease in CLR was 3 % and no patient showed a decrease of more than 20 %, which is in line with the results of other studies with 177Lu-Octreotate [177Lu-Octreotate, 14 % showed an annual improvement in CLR. Tumour response and improvement in clinical condition could explain the increase in CLR in these patients, since a rapid weight gain with stable serum creatinine values results in a higher CLR. Therefore, we suspect that the improvement in CLR did not reflect a true improvement in renal function.After PRRT with treotate , 17, 18.177Lu-octreotate is 3 to 4 years [177Lu-Octreotate.In practice, an annual decrease of 3 % means a CLR of 91 ml/min after 3 years in a patient with normal renal function at baseline , diabetes, hypertension, previous chemotherapy and poor baseline renal function [177Lu-Octreotate and/or 90Y-Octreotide. Hypertension was identified as a main risk factor for (persistent) nephrotoxicity. However, nephrotoxicity was defined as a categorical outcome according to CTCAE, neglecting the change in renal function over time. This can lead to a simplified representation of kidney toxicity after PRRT and false identification of risk factors. Valkema et al. analysed renal function in 37 patients treated with 177Lu-Octreotate by taking the subject-specific annual decrease in CLR extracted from fitted monoexponential curves [Several risk factors for kidney toxicity after PRRT with mainly function , 2, 4. Ifunction , renal f Given the repeated measurement structure of the data and the need to assess the effect of risk factors on both baseline CLR and change in CLR over time, a more advanced approach is required. We therefore used a mixed effects regression model. Mixed effects models are the standard modelling framework for the analysis of longitudinal data. These models explicitly account for differences in correlation structure of the data within/between patients and deal well with unbalanced data .In our present analysis, age >70 years and baseline CTCAE grade influenced the nonlinear model. However, the two risk factors only changed the estimated average baseline CLR component in our model, meaning that patients older than 70 years and/or patients with baseline CTCAE grade 2 had a lower estimated average CLR at baseline. None of the evaluated risk factors modified the percentage CLR change component significantly, implying that the percentage change in CLR over time in patients with risk factors was not different from that in patients without risk factors.177Lu-Octreotate is low and a higher number of patients would be required to show statistical significance of the risk factors. For the same reason, we were not able to compare patients with/without a solitary kidney and with/without alkylating chemotherapy (e.g. cisplatin). The relatively low numbers of patients resulted in low statistical power for testing these risk factors.An explanation for our results could be that the frequency of nephrotoxicity after PRRT with 99mTc-MAG3 (mercaptoacetyltriglycine) are used for accurate assessment of renal function in clinical practice [GFR measurement with inulin is the gold standard for measuring renal function, but practical implementation is difficult . Other rpractice . Howeverpractice , whereaspractice . All forpractice . Therefopractice , meaningRadiation toxicity dose effect models used in PRRT are predominantly based on the experience and knowledge obtained from EBRT. In the past, the threshold dose for late-stage kidney radiation damage for EBRT was set at 23 Gy . However90Y-DOTATOC, a correlation was found between the kidney absorbed dose and chronic kidney toxicity. The dose at which 5 % of patients will show kidney toxicity has been estimated at 24 Gy for 90Y-DOTATOC [90Y-DOTANOC [90Y irradiation and that for fractionated EBRT can be compared using the concept of the biologically effective dose (BED). BED is a measure of the true biological dose delivered at a particular dose rate and fractionation pattern, tissue-specific for a relevant biological end-point . It takes the protracted nature of the absorbed dose delivery by radionuclides into account by adjusting the kidney’s radiation sensitivity for the repair of sublethal radiation damage during the absorbed dose build-up according to the linear quadratic (LQ) model. The BED concept is thought to explain the 6-Gy higher dose limit than the 18 Gy accepted for EBRT [177Lu-Octreotate is provided in Table For PRRT with -DOTATOC . Another-DOTANOC . The absfor EBRT . Bodei e177Lu-Octreotate. Another argument for a higher dose limit is that 177Lu has shorter range β-particles than 90Y. This results in less damage to nearby nontarget tissue and  in fewer cases of nephrotoxicity at a fixed kidney dose [In this study, we did not find a significant difference in the effect of kidney dose on renal function. Most patients received a kidney dose of less than 28 Gy Fig. c. Howeveney dose –28.90Y-DOTATOC [1/2, which represents the damage and repair half-life in the BED model, however the two variables have an important effect on the dosimetric outcome [In PRRT studies, the LQ model concept of BED was first introduced with dosimetric data from 18 patients who received -DOTATOC . A stron-DOTATOC . In PRRT outcome , 31. Als177Lu-Octreotate. Therefore, in clinical practice, kidney dosimetry does not currently have a prominent place in PRRT with 4 × 7.4 GBq 177Lu-Octreotate. However, (serum-based) assessment of renal function during and after PRRT is mandatory since renal toxicity unrelated to PRRT could occur. Also measurement of renal function at baseline is required since low GFR is a risk factor for development of (sub)acute haematotoxicity after PRRT.Our results demonstrate that the kidneys are not the dose-limiting organ in patients treated with 177Lu-Octreotate is low. No patient showed (sub)acute grade 3 or 4 nephrotoxicity or an annual decrease in renal function of >20 %. No risk factors  leading to an additional annual decrease in renal function could be identified. Our study showed that the maximum radiation dose to the kidney adopted from EBRT and PRRT with 90Y-labelled analogues does not seem to apply to PRRT with 177Lu-Octreotate.The number of patients with nephrotoxicity after PRRT with ESM 1(DOCX 914 kb)Below is the link to the electronic supplementary material.


These different reflex responses coincided with differences in resting BRS  and resting HR  and were highly reproducible over time. In conclusion, we found distinct cardiovascular response patterns to sympathetic stimulation by LBNP in young healthy individuals. These patterns of preferential autonomic blood pressure control appeared related to resting cardiac BRS and HR and were consistent over time.In healthy subjects, variation in cardiovascular responses to sympathetic stimulation evoked by submaximal lower body negative pressure (LBNP) is considerable. This study addressed the question whether inter-subject variation in cardiovascular responses coincides with consistent and reproducible responses in an individual subject. In 10 healthy subjects , continuous hemodynamic parameters , and time-domain baroreflex sensitivity (BRS) were quantified during three consecutive 5-min runs of LBNP at −50 mmHg. The protocol was repeated after 1 week to establish intra-subject reproducibility. In response to LBNP, 5 subjects  showed a prominent increase in heart rate (HR; 54 ± 14%,  Lower body negative pressure (LBNP) is used in research settings as a model to study the cardiovascular effects of central hypovolemia in humans  and longer (1 week) time intervals.Ten healthy, non-smoking Caucasian subjects , with normal physical fitness and with a median (range) age of 22 (19–26) year, height of 174 (166–177) cm, and weight 69 (55–77) kg participated in this study. Exclusion criteria included a medical history of cardio- and/or cerebrovascular disease, neurological disorders, diabetes mellitus, regular fainting, and the use of medication (either prescription or non-prescription). Subjects abstained from heavy exercise and caffeinated beverages 5 h prior to the experiment. Phase of menstrual cycle in female subjects was not accounted for. Experiments were conducted in a temperature-controlled laboratory (20–22°C) at the same time of the day (12–4 p.m.) to avoid potential effects of circadian rhythm on the study outcomes. The institutional Medical Ethics Committee approved the protocol and written informed consent was obtained.Measurements were performed in a quiet room with subjects in the supine position. After instrumentation, the lower body was positioned inside the LBNP box  and sealed at the level of the iliac crest syncopal symptoms which were determined by one or more of the following criteria: systolic arterial pressure (SAP) below 80 mmHg, or rapid drop  by ≥10 mmHg/min), drop in HR by ≥15 bpm, and/or sweating, light-headedness, nausea, blurred vision, or skin pallor.Continuous arterial pressure (AP) was measured non-invasively by a volume clamp method using finger plethysmography . HR was expressed as the inverse of the inter-beat interval. Left ventricular stroke volume (SV) and cardiac output  were measured by a pulse contour method  which is validated against thermodilution estimates of CO  was analyzed using the cross-correlation method  comparing the last minute of rest with the last minute of LBNP . Intraclass correlation coefficients (ICC) and coefficients of variation (CV) were calculated  to assess intra-subject reproducibility. Intra-subject reproducibility was evaluated across LBNP trials  and sessions . One trial was defined as the last 3 min of rest, 5 min of LBNP and 2 min of recovery. ICC and CV values were calculated per trial time point and then averaged for all time points. No universal standard exists for classifying ICC and tests of statistical significance of reproducibility measures are of little practical utility , insufficient quality of Nexfin signals  or failure to reach the required LBNP pressure level . As a result, 54 LBNP trials entered final analysis. In a separate trial, integrity of the cardiovascular autonomic function was verified by passive head-up tilt testing (data not shown).A total of 60 LBNP trials were performed . Six LBNP trials were prematurely aborted due to a sudden drop in blood pressure (p < 0.001) increased with a fall in systolic  and mean arterial pressure , SV  and CO . Diastolic  pressure as well as TPR (p = 0.17) did not change. BRS decreased  in response to LBNP.Table p = 0.001) with no significant change in TPR (p = 0.25) vs. group B demonstrating a moderate increase in HR  and a rise in TPR . The response pattern of group A vs. B coincided with a larger decrease in SV  and BRS  see Figures p = 0.047) and higher resting BRS  were found in group A. Figure The cardiovascular compensatory response to LBNP differed between subjects Figure . Group AR p = 0.2 vs. grouFigure The findings of the present study provide important information regarding autonomic blood pressure control in humans. We observed distinct cardiovascular response patterns to sympathetic stimulation by LBNP in young healthy individuals. These patterns of preferential autonomic blood pressure control appeared related to resting cardiac BRS and HR. The finding that these patterns within an individual were consistent over a week suggest a programmed reflex response to sympathetic stimulation.The major neural pathway for acute BP regulation involves baroreflex function Rowell, . In respGenerally, subjects with high tolerance to central hypovolemia display signs and symptoms of greater sympathetic activition, e.g., higher HR and peripheral vasoconstriction with elevated neurohormonal activation  is not Hopkins, . SeveralA sudden blood pressure drop observed in two subjects (one from group A and one from group B) during the last LBNP trial of that session emphasizes that we do not know whether blood pressure control would have been maintained beyond the applied timeframe of simulated central hypovolemia. The finding that a decline in blood pressure is more likely to occur with accumulating exposure to LBNP conforms to previous research (Lightfoot and Tsintgiras, Sympathetic stimulation is considered to enhance specifically the inotropic condition and lusitropic properties of the healthy heart Thomas, . We acknWe did not evaluate MSNA respectively the sympathetic BRS response, which might provide further insight into the dichotomy.This study does not answer the question whether or not the distinct cardiovascular response patterns would have remained consistent over months or years. Convertino reported that re-testing after 1 year delivered comparable cardiovascular responses to LBNP (Convertino, In summary, the present study demonstrated distinct and reproducible cardiovascular response patterns to sympathetic stimulation by central hypovolemia in young healthy adults. Differences in resting HR and BRS between subjects suggest individually programmed reflex strategies of autonomic blood pressure control which may contribute to the variance observed in cardiovascular reflex responses to central hypovolemia. The mechanisms responsible for this phenomenon and the extent to which they operate in other groups of subjects deserve attention.A-SGT Bronzwaer and J Verbree contributed to the experimental design, data acquisition, data analysis, data interpretation, and writing the manuscript. WJ Stok contributed to data analysis and manuscript revision. MA van Buchem and MJAP Daemen contributed to data interpretation and manuscript revision. MJP van Osch contributed to experimental design, data interpretation, and writing the manuscript. JJ van Lieshout supervised the study, contributing to the experimental design, data analysis, data interpretation, and writing the manuscript. All authors approved the final version of the manuscript.The authors thank the Rembrandt Institute of Cardiovascular Science for support.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The most prevalent form of hypertension is systolic blood pressure (SBP) and it is considered to be predisposing risk factor for cardiovascular disease. The objective of the study was to assess self-care practices, knowledge and awareness of hypertension, especially related to SBP among cardiac hypertensive patients.A Cross sectional study was conducted on 664 cardiac hypertensive patients, which were selected by non-probability convenience sampling from cardiology outpatient department of three tertiary care hospitals. Face to face interviews were conducted using a pre designed questionnaire. Data was entered and analyzed by SPSS (V17).81.8%, did not know that hypertension is defined as high blood pressure. 97.1% of the sample population did not know that top measurement of blood pressure was referred to as systolic and only 25.0% correctly recognized normal systolic blood pressure to be less than 140mmHg. 7.4% of the patients consulted their doctor for hypertension once or twice in a month. Risk factor for high blood pressure most commonly identified by the participants was too much salt intakeThe results state that there is an inadequate general knowledge of hypertension among cardiac patients and they do not recognise the significance of elevated SBP levels. There is a need to initiate programs that create community awareness regarding long term complications of uncontrolled hypertension, particularly elevated SBP levels so that there is an improvement in self-care practices of the cardiacpatients. Considered as the silent killer , high arIn Pakistan one in every three individual over the age of 45 years is hypertensive as revealed by the National Health Survey (NHS) . AccordiLocal data in relation to cardiac hypertensive patients is scarce, which made it necessary to conduct this study in this area to determine the association of knowledge of SBP and CVD in cardiac hypertensive population. This can help us modify the treatment options, reduce adverse outcomes and provide better health care services. The objective of the study was to assess self-care practices, knowledge and awareness of hypertension, especially related to SBP among cardiac hypertensive patients attending cardiology outpatient department (OPD) of tertiary care hospitals.A descriptive, cross-sectional study was conducted to evaluate the knowledge, awareness and self-care practices of hypertension among cardiac hypertensive patients. Six-sixty four patients were interviewed from the cardiology outpatient department to obtain the required information. The sample size of 664 was determined assuming percentage knowledge of HTN among cardiac patients to be 50% (taking 99% level of significance and 1% confidence limit). The blood pressure of patients was inquired by directly asking them. The study was performed after the approval from the Institutional Review Board of the Dow University of Health Sciences.A multi-center study was conducted at the cardiology OPD of National Institute of Cardio-Vascular Diseases (NICVD), Abbasi Shaheed Hospital and Civil Hospital, Karachi. The NICVD being the largest cardiovascular tertiary care hospital of Karachi, receives patients from all over Karachi, and even from the remote areas of Sindh; while the other two, located at the two ends of the district, make it possible to cover patients from different areas of Karachi. The patients from the OPD were selected by non-probability convenience sampling, over a period of one week to prevent repetition of participants in the sample. Patients aged below 18 and pregnant women were excluded from the population, and so were the patients presenting with complications of hypertension like stroke, cerebrovascular accidents etc. and patients presenting with co morbidities like diabetes mellitus and renal failure. While the inclusion criteria included patients who were 18 and above, suffering from known pathology of valvular, ischemic heart disease or both. A patient was considered as hypertensive if he has BP > 140/90 mm of Hg or a lower BP on anti-hypertensive drugs. An interview based questionnaire was presented to each of the participant by the researcher in the homogeneous manner to limit interview biases. The first part of the questionnaire comprised of patients demographics followed by the clinical history of the patient; the second part dealt with the knowledge and awareness of hypertension with special relation to SBP, and the last part was regarding the self-care practices and management of hypertension.The collected data was entered on SPSS (V17) software. The same software was used for data management and analysis. Mean and standard deviation were calculated for all quantitative variables like age, SBP and DBP etc. Frequency and percentages were calculated for all qualitative variables like gender etc. Chi-square test was used to find out the association benefits of study between outcome variable (knowledge of HTN) and other factors like gender, education and socio-economic status.A total of 664 cardiac hypertensive patients were included in the study consisting of 422 males and 242 females, giving a male to female ratio of 1.7:1. participants, 597(89.9%), were using medications for hypertension. Most of the cardiac hypertensive patients, 169 (25.5%), said that they were hypertensive from a time period of 6 months-2 years. Out of 664 participants, 347 (52.3%) were aware of their blood pressure reading on their last visit which had a mean systolic blood pressure (SBP) of 144.6 mm Hg (SD=33.2 mm Hg) and mean diastolic blood pressure (DBP) of 94.0 mm Hg (SD=23.7 mm Hg). No family history of any disease was found in 48.5% (N=322) of the participants, however majority of the remaining participants had a family history of cardiovascular disease, .Furthermore, 85.8% (N=570) of the patients claimed hypertension to be very dangerous and 89.6% (N=595) agreed that controlling blood pressure can improve a person’s health. Five hundred and forty three (81.8%) did not know that hypertension is defined as high blood pressure. Five hundred and twenty (78.3%) believed that it’s very important to take medicines to keep blood pressure under control. Majority of the sample population, 97.1% (N=645), did not know that top measurement of blood pressure was referred to as systolic and 96.8% (N=643) did not know that bottom measurement of blood pressure was referred to as diastolic. Participants who either did not know or identified normal systolic blood pressure (SBP) to be equal to 140mm Hg or greater than 140mm Hg were 50.2% of the sample population. In case of normal diastolic blood pressure (DBP), 52.6% of the participants did not know or identified the value to be equal to 90mm Hg or greater than 90mm Hg. When asked, which measure do you think is important, 70.9% were unaware. A similar outcome was seen when asked about the number responsible in causing cardiovascular disease, and 83% (N=551) of them did not know. Two hundred and thirty seven patients (35.7%) claimed to have high blood pressure at their last checkup. Results of questions relating to hypertension knowledge in cardiac hypertensive patients are given in Further analyses were performed using demographic characteristics in which these outcomes were statistically analyzed. In general, there were no specific differences in knowledge, awareness, or self-care practices among the subgroups. Patients who had a master’s degree showed better understanding of hypertension than comparatively less educated patients. These patients specifically showed a better knowledge of the definition of hypertension . In addition, businessmen tend to report better knowledge of hypertension compared to patients with other professions .Participants with a better socioeconomic status were seen to carry out more self-care practices compared to people with low monthly household income .A descriptive study was conducted to assess the up-to-date information on knowledge, awareness and self-care practices of HTN among cardiac hypertensive patients in Karachi. We found that the awareness level of cardiac hypertensive patients in general is inadequate. The patients are not informed about recently recommended guidelines, cutoff values of SBP and association of their SBP levels with cardiovascular disease. Consequently, 48% of the patients could not recall their BP value and were unable to report whether their BP value is elevated or normal. Our results also revealed insufficient self-care practices of cardiac patients towards their BP control. However, prompt management leads to lower incidence of complications  and reduAlarmingly, very limited numbers of cardiac patients (8%) were aware about the correct definition of HTN and majority of the patients (82%) did not know anything about this term. Less than 3% could identify the top and bottom number of BP reading as systolic and diastolic correctly. This reveals poor awareness level of the participants. This is fairly consistent with the findings of another Pakistani study which has also narrated inadequate awareness among hypertensive patients . HoweverIt was reassuring to see that majority of the patients were knowledgeable about the seriousness of the condition to their health due to uncontrolled BP. Ninety percent of the patients knew that lowering BP would improve a person’s health and that they could lower their uncontrolled BP by adjusting their lifestyle. The results are in line with the international study conducted by Susan et al. . This shDuring recent years, SBP has been recognized as the greatest causative agent for the morbidity and mortality associated with CVD and stroke . In seveA large number of participants considered salt intake as the risk factor to be associated with high BP, which is evident from a study done on British population  and in lFurthermore, patient’s regularity on visiting doctor for HTN and cardiologist for their cardiovascular exam, including ECG and cholesterol level, and having home sphygmomanometer was found to be very low. The results could be attributed to less affordability as most of the patients belonged to low socio-economic status. The attitude of patients to bring about lifestyle changes like rhythmic exercise, weight reduction and less stress was significantly less. This might be because of the perception that lifestyle changes have no impact on high BP management as shown by Aubert . AccordiTo the best of our knowledge, our research has comprehensively evaluated HTN knowledge especially related to SBP among cardiac patients along with their self-care practices involved in the management of high BP. However, there were a few limitations to our study. Most of the participants belonged to low socioeconomic status and had no education. So the results cannot be generalized to the entire population. Secondly, our sample does not include those who were unstable to attend cardiology OPD. Their views may vary over knowledge and self-care practices of HTN. Apart from this we did not obtain the BP values from medical records for the participants who could not recall their last BP reading.According to our results, there is an inadequate general knowledge of hypertension in cardiac patients. Patients do not recognize the significance of elevated SBP levels. The study helped us identify the areas that need to be considered by the awareness programs. People should be encouraged to have their blood pressures checked regularly, especially when they have a family history of hypertension. There is a need to initiate programs that create community awareness regarding long-term complications of uncontrolled hypertension in cardiac patients, particularly elevated SBP levels. Improvement in self-care practices can decrease the mortality rate associated with hypertension.


The purpose of this study was to determine whether Eadyn can be used to predict the decrease in arterial pressure when decreasing the NE dosage in resuscitated sepsis patients.Gradual reduction of the dosage of norepinephrine (NE) in patients with septic shock is usually left to the physician’s discretion. No hemodynamic indicator predictive of the possibility of decreasing the NE dosage is currently available at the bedside. The respiratory pulse pressure variation/respiratory stroke volume variation .A prospective study was carried out in a university hospital intensive care unit. All consecutive patients with septic shock monitored by PICCOn = 13). Clinical characteristics appeared to be similar between responders and nonresponders. Eadyn was lower in responders than in nonresponders (0.75 (0.69 to 0.85) versus 1 (0. 83 to 1.22), P <0.05). Baseline Eadyn was correlated with NE-induced MAP variations . An Eadyn less than 0.94 predicted a decrease in arterial pressure, with an area under the receiver-operating characteristic curve of 0.87 : 0.72 to 0.96; P <0.0001), 100% sensitivity, and 68% specificity.In total, 35 patients were included. MAP decreased by >15% after decreasing the NE dosage in 37% of patients (dyn may predict the decrease in arterial pressure in response to NE dose reduction. Eadyn may constitute an easy-to-use functional approach to arterial-tone assessment, which may be helpful to identify patients likely to benefit from NE dose reduction.In sepsis patients treated with NE, Ea Vasopressors are an essential part of the early management of patients with circulatory shock . TreatmeNorepinephrine (NE) is recommended in national and international guidelines as first-line hemodynamic support for septic shock . In the dyn) [dyn was also able to predict the hemodynamic response in mean arterial pressure (MAP) to fluid administration in hypotensive, preload-dependent patients [dyn can therefore constitute a functional approach to the assessment of arterial tone similar to preload responsiveness parameters that are used to predict the hemodynamic response to a change in cardiac preload [The ∆respPP/∆respSV ratio has recently been proposed as a dynamic indicator of arterial tone  ,11. Sevedyn) ,13. Eadypatients . Eadyn c preload -14.The primary objective of this study was to answer the following question: can dynamic arterial elastance be used to predict the decrease in arterial pressure induced by decreasing the NE dosage in sepsis patients? We also describe the effect of decreasing the NE dosage in resuscitated septic shock patients.This study was approved by the Institutional Review Board (IRB) for human subjects . Informed consent was waived, as the IRB considered the protocol to be an observational study. In our institute, the dosage of NE is decreased by 3.3 μg/min each hour for as long as MAP remains higher than 65 mm Hg. The indication to decrease the dosage of NE was left to the physician’s discretion. Only a one-step NE dose reduction was assessed in this study.A prospective, observational study was conducted at Amiens University Hospital intensive care unit over a period of 12 months (2012). Inclusion criteria were all consecutive patients with a diagnosis of severe sepsis or septic shock, according to the criteria of the Surviving Sepsis Campaign, treated with NE, for whom the attending physician decided to decrease the NE dosage, and who were monitored with a PICCO monitoring device . Exclusi2 monitoring device was used to measure cardiac output (CO). Estimation of stroke volume by pulse-contour analysis was calibrated by transpulmonary thermodilution with injection of three 15-ml boli of cold saline. The mean value of three consecutive measurements was used for analysis of stroke volume (SV), CO, global end-diastolic volume (GEDV), and cardiac function index (CFI). If the difference between the three values was greater than 10%, two additional measurements were subsequently performed. Respiratory variations of pulse pressure (∆respPP) and stroke volume (∆respSV) were monitored by using PICCO2. Each value was the average of five consecutive measurements. Central venous pressure (CVP) and blood pressure were measured with a transducer zeroed at the level of the midaxillary line.An internal jugular vein central venous catheter was placed in all patients, and a thermistor-tipped arterial catheter  in the femoral artery connected to a PICCOdyn) was defined as the ratio of ∆respPP to ∆respSV. Static arterial compliance (C) (ml/mm Hg) was calculated as the ratio of SV to pulse pressure [The following clinical parameters were recorded: age, gender, weight, surgical/medical history, main diagnosis, and IGS2. Heart rate (HR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), CVP, ∆respPP, ∆respSV, CO, systemic vascular resistance (SVR), and GEDV were recorded at baseline, with the patient adapted to the ventilator. A passive leg raising (PLR) test was performed to evaluate the effects on pulse-contour analysis of CO . The dospressure .Ventilator settings were maintained at constant levels throughout the study period. Thermodilution calibration was performed before and after decreasing the dose of NE.dyn can predict a decrease in arterial pressure in response to decreasing the NE dosage with an AUC greater than 0.80, a power of 80%, an alpha risk of 0.05, and a beta risk of 0.2. Thirty-five patients were therefore recruited by taking into account the exclusion criteria. The distribution of the variables was assessed by using D’Agostino-Pearson test. Data are expressed as proportion (percentage), mean (standard deviation), or median (25th to 75th percentiles), as appropriate. Nonresponders and responders were defined by MAP variation (expressed as a percentage) after decreasing the dose of NE. A positive response was defined as a ≥15% decrease in MAP [t test, Student t test, and Mann–Whitney test were used to assess statistical significance, as appropriate. Linear correlations were tested with the Spearman rank method. A receiver-operating characteristic curve (ROC) was established for SVR, arterial compliance, and Eadyn. The test previously described by DeLong and colleagues was used to compare areas under the ROC curve (AUC) for each variable. Differences with a P value <0.05 were considered statistically significant. Medcalc 12.7.7.0 software  was used to perform statistical analysis.A sample of 30 patients would be sufficient to demonstrate that Eae in MAP . The nonThirty-five patients with septic shock monitored by PICCO2 were included. The most common cause of septic shock was pneumonia and peritonitis Table . Patient; in pressure-nonresponder patients, the dosage of NE was decreased from 0.38 (0.12 to 1.2) to 0.34 (0.09 to 1.2) μg/kg/ min. The median dose was not statistically different between the two groups (P = 0.43). The dosage of norepinephrine was decreased by 3.3 μg/min in all patients. At baseline, eight patients had ∆respPP and/or ∆respSV >15%. Apart from these patients, two were classified as pressure responders. Baseline CO variations in response to PLR were not significantly different between responders and nonresponders (1.6% (−4 to 8) versus 2.1% (−1 to 6), P = 0.87). SV decreased by more than 15% after decreasing the norepinephrine dosage in two patients.In pressure-responder patients, the dosage of NE was decreased from 0.25 (0.14 to 0.58) to 0.23 (0.1 to 0.54) μg/kg/mindyn was lower in patients in whom arterial pressure decreased after decreasing the dose of norepinephrine , but no correlation was observed between SVR, SV variations, and a decreased dosage of NE . Eadyn was not correlated with norepinephrine dose .Eadyn predicted the decrease in arterial pressure with an AUC of 0.87   and 0.54 , respectively.In the overall population, Eadyn may be a functional indicator of arterial tone when decreasing the dose of NE that can differentiate patients in whom MAP is maintained from those in whom MAP decreases in response to a fixed dose reduction. An Eadyn less than 0.94 predicted a 15% decrease in MAP in response to decreasing the dose of NE. (b) The arterial pressure change associated with decreasing the dose of NE may be mostly due to the arterial vasoconstrictor (α-adrenergic) effect of NE.This study, conducted on resuscitated sepsis patients, demonstrated that (a) Eadyn has recently been proposed as a marker of arterial tone or, more specifically, a marker of arterial stiffness [dyn, whereas norepinephrine infusion increased this indicator [dyn less than 0.9 was predictive of persistent arterial hypotension after fluid challenge, despite an increase in CO. [dyn was found to discriminate successfully responders and nonresponders to dose de-escalation with volume expansion [No study has previously evaluated the predictive value of an indicator for NE dose reduction in septic shock patients. Eatiffness . In postndicator . In ICU e in CO. . In surgxpansion .dyn can identify patients in whom arterial pressure will decrease in response to NE dose reduction. Moreover, only Eadyn was predictive of the decrease in arterial pressure with a cut-off value close to previously published values [In the present study, we demonstrated that Ead values ,13.dyn may indicate in which part of the curve the patient is situated. Eadyn may constitute a functional approach to arterial tone assessment in the same way as preload responsiveness indices that are used to predict fluid responsiveness to a change in cardiac preload [dyn was lower in pressure responders, suggesting that SV variations induced low variations in PP due to the lower central vasomotor tone. Decreasing the NE dosage induced increased arterial compliance, which was even more marked in pressure responders. As discussed later, NE dose reduction induced only arterial α-adrenergic effects with no change in cardiac preload and CO. These effects may have been less marked than those observed in previous studies because of the limited decrease of the NE dose [dyn. Because SV did not vary significantly, the decrease in arterial pressure (MAP and PP) was associated with changes in SVR and arterial compliance after the decrease of the norepinephrine dosage.Arterial pulse pressure results from the interaction between the blood volume ejected from the ventricle and the arterial system, which comprises several phenomena: stroke volume (SV), arterial wave reflection, wall stiffness, total peripheral resistance. The relation between arterial pressure and arterial volume is curvilinear . In this preload ,14. Eady NE dose ,18, but SVR was not significantly different between the two groups of patients and did not predict the subsequent course of arterial pressure. These results may be because SVR reflects a pressure difference between MAP and CVP, whereas, from a physiological point of view, the cardiovascular system comprises two pressure systems with a waterfall phenomenon . SVR theIn the present study, the vascular effects of NE may depend on the sepsis patient’s underlying cardiovascular state. The vascular response observed differed from that reported in previous published studies ,18,20. SAnother explanation could be that the dose of NE was not sufficiently decreased to induce any effects on venous return and cardiac preload ,20. The dyn, arterial pressure did not decrease by more than 15%. These results are in accordance with those reported by Hadian and colleagues [dyn was not correlated with changing doses of vasoactive drugs. Nevertheless, Eadyn had a high negative predictive value, showing that the upper Eadyn cut-off value of 0.94 is highly predictive of successful NE dose reduction.Our results must be interpreted cautiously, as up to 18% of patients had a false-positive response: despite a low Ealleagues , who obsAnother explanation could be that the dosage of NE was not decreased sufficiently in these patients to induce any significant vascular effects. This indicator was not sufficiently specific to contraindicate NE dose reduction by physicians/nurses at the bedside.dyn are needed to confirm the performance of this bedside indicator to adjust the NE dosage. Our sample size was small but the study was constructed to demonstrate the ability of Eadyn to predict changes of MAP associated with decreasing the NE dosage. Some of the differences observed for hemodynamic parameters might have reached statistical significance with a larger patient cohort, although the directional changes would unlikely be reversed. We studied a one-step NE dose reduction that was the same for the overall population. As no further decrease in the NE dosage was evaluated, we cannot draw any conclusions concerning the subsequent course of hemodynamic parameters and Eadyn in response to a more marked reduction of the NE dose. We studied MAP changes only due to changes in NE doses and not due to other therapeutic interventions . These results cannot be extrapolated to patients concomitantly treated with dobutamine, who may represent up to 30% of all sepsis patients.Further prospective interventional studies using algorithms with Eadyn was probably marginal, as ventilatory parameters were kept constant during the study period. This relation remains constant and predictive, even during spontaneous ventilation, provided that ∆respPP and ∆respSV values are sufficiently large to define a slope [Another limitation could be mechanical ventilation that alters the predictability of volume-responsiveness indices. The influence of tidal volume on Ea a slope ,22. Ther a slope .We used the PiCCO™ that does not report individual SV values on a beat-to-beat basis. ∆respSV and ∆respPP represent an average over 30 seconds. CO was calculated by using an algorithm based on the ventriculo-arterial coupling transfer function with thermodilution calibration for CO measurement. As a thermodilution calibration was performed before/after changing the NE dosage, we can assume that ∆respSV was calibrated to the change of vascular tone induced by NE.dyn less than 0.94 was predictive of a decrease of arterial pressure in response to a decrease of the norepinephrine dosage in resuscitated sepsis patients. In contrast, no other hemodynamic variables were found to be predictive of a decrease in arterial pressure. Eadyn may constitute an easy-to-use functional approach to arterial tone assessment and may be helpful to identify patients likely to benefit from NE dose reduction. The high negative predictive value of this indicator can identify patients with a minimal risk of decreased arterial pressure. Further studies using algorithms with Eadyn are necessary to confirm the value and effectiveness of such an indicator at the bedside to adjust the NE dosage.In this study, an Ea• Dynamic arterial elastance can be used to predict a decrease of arterial pressure associated with decreasing the norepinephrine a-dosage in sepsis patients.• Systemic vascular resistance cannot predict the decrease of arterial pressure associated with decreasing the norepinephrine dosage in sepsis patients.• The arterial pressure decrease associated with decreasing the norepinephrine dosage may be mostly due to the arterial vasoconstrictor effect of norepinephrine.


Background. We propose a 1-1-12 wash-in scheme for desflurane-nitrous oxide (N2O) low-flow anesthesia. The objective of our study was to determine the time to achieve alveolar concentration of desflurane (FAD) at 1, 2, 3, 4, 5, and 6%. Methods. We enrolled 106 patients scheduled for elective surgery under general anesthesia. After induction and intubation, wash-in was started with a fresh gas flow (FGF) of N2O : O2 1 : 1 L min−1 and vaporizer concentration of desflurane (FD) of 12%. Ventilation was controlled to maintain PACO2 at 30–35 mmHg. Results. The FAD rose rapidly from 0 to 4% in 2 min in a linear manner in 0.5 min increments. An FAD of 6% was achieved in 4 min in a linear fashion from FAD of 4% but in 1 min increments. An FAD of 1 to 6% occurred at 0.6, 1, 1.5, 2, 3, and 4 min. Heart rate during wash-in showed a statistically, albeit not clinically, significant pattern of increase. By contrast, blood pressure slightly decreased during this period. Conclusions. We developed a 1-1-12 wash-in scheme using a FGF of N2O : O2 1 : 1 L min−1 and FD of 12% for desflurane-nitrous oxide low-flow anesthesia. A respective FAD of 1, 2, 3, 4, 5, and 6% can be expected at 0.6, 1, 1.5, 2, 3, and 4 min. A sccticable . We propAD at 1, 2, 3, 4, 5, and 6% using the 1-1-12 wash-in scheme.The aim of this study was to determine the time to achieve Fhttp://www.clinicaltrials.gov (NCT01348984). All patients gave written informed consent before recruitment.The current study was approved by the Institutional Review Board of Khon Kaen University (HE561247) and it was registered at AD of 6%. With the total width of the expected confidence interval of 16 sec and a significance criterion of 0.05, the total number of patients required was 96. To cover a 10% dropout, 106 patients were recruited. We included patients between 18 and 64 years of age, having an ASA physical status of I or II and scheduled for elective surgery under general anesthesia with endotracheal intubation and controlled ventilation. We excluded patients with pulmonary or cardiac disease, a BMI > 30 kg m−2, and any contraindication of use of succinylcholine and nitrous oxide.Our study was a descriptive trial. We calculated the sample size from a pilot study on 10 patients, which identified a standard deviation of 40 sec at Fμg kg−1, the patient was induced with propofol at 2 mg kg−1. Endotracheal intubation was facilitated with succinylcholine at 1.5 mg kg−1. After the correct position of the tube was confirmed, ventilation was controlled using a FGF of N2O : O2 1 : 1 L min−1 and FD of 12%. The tidal volume was initially set at 7 mL kg−1 at a respiratory rate of 12 min−1 and then adjusted to keep the PACO2 around 30–35 mmHg. We recorded (a) the time to achieve FAD at 1, 2, 3, 4, 5, and 6%, (b) FID, (c) blood pressure, and (d) heart rate. After FAD 6% was achieved, the FGF of N2O : O2 was reduced to 0.5–1.0 L min−1 and the FD was adjusted according to the judgment of the anesthesiologist.All patients received standard intraoperative monitoring and care. The monitoring consisted of ECG, pulse oximeter, noninvasive blood pressure, capnography, and anesthetic gas analysis. The combined anesthetic machine and gas analyzer used in this study was the Dräger Primus . We used a standard circle circuit with a soda lime absorber. Blood pressure and heart rate were recorded before induction for a baseline. After injecting the premedication intravenous fentanyl of 1 rANOVA), P < 0.05 was considered statistically significant.Statistical analyses were performed using SPSS for Windows 16.0. The continuous demographic data are presented as means ± SD and the categorical as the number of patients (percentage). The primary outcome was presented as a mean ± SD and 99% confidence interval (CI). The blood pressure and heart rate at different times were compared using repeated measures analysis of variance  significant increase . In contID remains low and it takes more time to rise than using a high FGF. Thus, LFA needs an initial high FGF or low FGF with the FD set close to the maximal setting in order to shorten the time needed to achieve a therapeutic level, called the wash-in phase [The purpose of induction and maintenance of inhalation anesthesia is to bring the patient from Guedel's classification of anesthesia stage 1 to stage 3—where the patient are to be maintained—as rapidly as possible to avoid the unpleasant phenomena of stage 2. With current intravenous drugs—for example, propofol, thiopental, and etomidate—the onset is rapid (within one minute) by rapid first compartment distribution. By contrast, current modern inhalation anesthetics—for example, isoflurane, sevoflurane, and desflurane—require a longer time to achieve a minimum alveolar concentration (MAC) with high FGF and even much longer with LFA. LFA is gaining in popularity because of its many benefits—that is, economic benefit, less pollution, conservation of heat and humidity, and availability of modern anesthesia machines and monitors. With LFA, less inhalation anesthetic is delivered into the circle circuit, so the Fin phase .2O of 60–70% in O2 at FGF of 4.4 L min−1 plus FD in the range of 3.4 to 8.7%, which resulted in the FAD reaching values in the range of 90–95% of the fresh gas concentration within 10–15 min [2 3.5 L min−1 and a FD at 3 MAC, an FAD of 1 MAC could be achieved within 1 min [AD exceeded 1 MAC by 2 min and remained above this value throughout the study [2O : O2 4 : 2 L min−1 with FD of 6.5% for 15 min that could achieve an FAD of 4.5% [−1) with an FD of between 0.5 and 3 MAC, which can only achieve a few of the specified FAD targets. Hendrickx et al. later proposed an empirical logistic regression model for predicting the entire range of FGF/FD combinations with clinically acceptable accuracy, from a FGF as low as 1 L min−1, for attaining the target FAD within 5 min [Baum et al. developed a dosing scheme using NID—the effect of FGF and FD—can be increased by using a very high FGF (>3.5 L min−1) with a moderate FD or a low range of high FGF (2 L min−1) with a high FD. We developed a wash-in scheme, adapted from the logistic regression model of Hendrickx et al. [−1 with an FD of 12% (approximately 2 MAC), resulting in a rapid rise of the FID. From visual inspection of the trajectories of time to achieve each FAD in 2O in our scheme because of its second gas effect [AD from 1 to 6%, which is 2-MAC equivalent with 50% N2O, at 0.6, 1, 1.5, 2, 3, and 4 min. This range covers the FAD required for both balanced and pure inhalation anesthesia. The fact that this scheme can achieve FAD of 6% within 4 min makes it ideal for inhalation anesthesia initiation without hyperexcitation. After achieving the required specific target, one can reduce the FGF to LFA range of 0.5 to 1 L min−1 and maintain the target FAD by simply setting the FD above the target by 1-2% [Fx et al. , using as effect  and addis effect . Our schAD to a target lower than the concentration required to block autonomic reflexes to nociceptive stimuli (MACBAR) of desflurane of 1.5 to 1.7 MAC, such slow increase of FAD keeps the patient in the second stage longer. Our scheme results in a rapid wash-in, thereby passing the MACBAR of desflurane earlier and maintaining the patient in the surgical stage throughout the study without sympathetic overactivity.Although we found a significantly increased heart rate and decreased blood pressure during the wash-in period, the magnitude is without clinical significance as noted by Warltier and Pagel . By cont2O as part of the carrier gas, this scheme may not be inferred to the cases contraindicating the use of nitrous oxide. This scheme may have a limitation for use in obese patients since we excluded patients with a BMI > 30 kg m−2. Further study for such situations is required.Since our scheme uses N2O : O2 1 : 1 L min−1 and FD of 12% for desflurane-nitrous oxide low-flow anesthesia in patients requiring general anesthesia with endotracheal intubation and controlled ventilation. A respective FAD of 1, 2, 3, 4, 5, and 6% can be rapidly expected at 0.6, 1, 1.5, 2, 3, and 4 min. This technique proved practicable and it covered the FAD required for both balanced and pure inhalation anesthesia; there was a nonclinically significant increase in heart rate and decrease in blood pressure during the wash-in period.We developed a 1-1-12 wash-in scheme using a simple, single-step FGF of N


Magnetic resonance imaging with arterial spin labeling (ASL) is a noninvasive approach to measure organ perfusion. The purpose of this study was to evaluate the reproducibility of ASL kidney perfusion measurements with semiautomatic segmentation, which allows separate quantification of cortical and medullary perfusion.The right kidneys of 14 healthy volunteers were examined 6 times on 2 occasions (3 times at each occasion). There was a 10-minute pause between each examination and a 14-day interval between the 2 occasions. Cortical, medullary, and whole kidney parenchymal perfusion was determined with customized semiautomatic segmentation software. Coefficient of variances (CVs) and intraclass correlations (ICCs) were calculated.P > 0.05; R2 = 0.60/0.59/0.54). For whole, cortical, and medullary kidney perfusion, the total ICC/CV were 0.97/3.43 ± 0.86%, 0.97/4.19 ± 1.33%, and 0.96/4.12 ± 1.36%, respectively. Measurements did not differ significantly and showed a very good correlation .Mean whole, cortical, and medullary kidney perfusion was 307.26 ± 25.65, 337.10 ± 34.83, and 279.61 ± 26.73 mL/min/100 g, respectively. On session 1, mean perfusion for the whole kidney, cortex, and medulla was 307.08 ± 26.91, 336.79 ± 36.54, and 279.60 ± 27.81 mL/min/100 g, respectively, and on session 2, 307.45 ± 24.65, 337.41 ± 33.48, and 279.61 ± 25.94 mL/min/100 g, respectively (ASL kidney measurements combined with operator-independent semiautomatic segmentation revealed high correlation and low variance of cortical, medullary, and whole kidney perfusion. In this context, it is of importance to assess renal perfusion.4 However, these surrogate parameters have a limited sensitivity to alterations in renal physiology. Furthermore, changes in these parameters may occur at a later stage during the development of kidney disease or may even be normal despite a significant compromise in renal perfusion . These limitations are not only important for patient care but also in clinical research.There are different methods available for kidney perfusion measurements. In diverse clinical settings, renal function is usually assessed with the estimated glomerular filtration rate, which is commonly estimated from serum values of endogenous markers .5 However, this process is labor-intensive, time consuming, expensive, invasive, and bears potential side effects, such as anaphylaxis. Furthermore, it does not allow assessment of the different compartments of the kidney. Doppler sonography is a noninvasive procedure to detect renal artery stenosis or alterations in the peripheral vessel resistance, but does not allow accurate quantification of the tissue perfusion8 and does not reflect renal vascular resistance.9 Moreover, measurements of global kidney function are not suitable for the detection of diminished function in restricted areas or compartments .10 Radionuclide scintigraphy is invasive due to the use of an exogenous radioactive tracer, limiting its use in clinical trials and under special conditions .12 Dynamic perfusion studies performed using both computed tomography (CT) or magnetic resonance imaging (MRI) require administration of an exogenous contrast compound that may be nephrotoxic  and that also involves an ionizing radiation exposure. Paramagnetic gadolinium-based contrast agents for MRI, while generally safe, are not suitable for use in patients with advanced renal impairment due to the minor but potential risk for the development of nephrogenic systemic fibrosis.13Clearance techniques are conventionally used to measure effective renal blood flow, with the para-aminohippurate (PAH) clearance being the gold standard.15 With respect to the kidneys, ASL approaches, including the FAIR True-FISP technique, have recently been demonstrated to produce clinically valuable perfusion measurements.19 Several studies have investigated changes in renal perfusion with MRI techniques.21 A significant decrease in renal perfusion was reported in patients with renal artery stenosis.22 Regional differences of microcirculation have been reported in renal cell carcinomas24 and renal allografts.25 Most ASL imaging in the literature was carried out with widely available MR scanners having a field strength of 1.5 Tesla.28 Therefore, ASL represents a noninvasive method to measure renal perfusion without exposure to ionizing radiation or exogenous contrast agents.Therefore, a noninvasive, reproducible, and quick method to quantify kidney perfusion is desirable. Due to its high perfusion rate, the kidney is an appropriate candidate for perfusion imaging with MRI utilizing arterial spin labeling (ASL), which uses magnetically labeled protons in the blood as an endogenous contrast agent. Hence, the administration of a contrast agent is not necessary. In recent years, several ASL techniques, including the flow-sensitive alternating inversion recovery (FAIR) technique, have been developed mainly to measure perfusion of the brain.29 reported a mean image analysis time of approximately 30 minutes per kidney. Therefore, the purpose of this study was to investigate the reproducibility of ASL combined with semiautomatic segmentation of the renal compartments, which allowed the differential quantification of cortical and medullary perfusion at 1.5 Tesla MRI.One current constraint is the time consumption and operator dependence required for image analysis. Gillis et al2. All subjects had an estimated glomerular filtration rate >60 mL/min/1.73 m2 (MDRD formula) at baseline. The average office blood pressure at baseline was 133 ± 16/82 ± 10 mm Hg. The study recruitment, which was started in July 2014, was conducted by advertisement in local newspapers. All patients gave written informed consent and the study was executed according to the Declaration of Helsinki and “good clinical practice” (GCP) guidelines. There were 2 drop-outs, one caused by an abnormal anatomy of the kidney and the other caused by breathing artifacts. Subjects were examined 2 times with an interval of 2 weeks. At each time point, 3 measurements of 10 minutes each with a rest period of 10 minutes between the measurements were performed. Overall, 6 measurements on each patient were performed. At both time points the examinations were performed within 1 hour at the same time of day.This pilot study included 14 subjects; 5 healthy volunteers and 9 hypertensive patients with controlled blood pressure. Mean age was 48 ± 13 years and 9 subjects of the total cohort were male . The body mass index of all subjects was on average 27 ± 5.2 kg/m16ASL was performed with a 1.5 Tesla MRI scanner  using a FAIR True-FISP sequence. The FAIR and true fast imaging with steady-state precession (True-FISP) approach combines a FAIR perfusion preparation and a True-FISP data acquisition strategy. The perfusion measurement is based on 2 data acquisitions, one with a global inversion prepulse, followed by one with a slice selective inversion (FAIR). The prepulses lead to a labeling of blood water spins. In contrast to the global inversion prepulse, the slice selective inversion prepulse only labels the blood water spins inside the kidney but not the inflowing blood water spins. Subtraction of both images therefore reflects the local perfusion. A 3rd image without the FAIR preparation pulse was measured to normalize the signal intensities on each patient. The technical and theoretical background of the sequence has been previously described in detail.MRI, as performed in the current study, is illustrated in Figure 17 Since this computation is performed at pixel level, precise registration of these images is crucial. However, patient movement during acquisition and fluctuations in the breath-hold results in a shift of the kidney. To counteract these effects, we chose a simultaneous segmentation/registration approach based on the software presented by Siegl et al.30 One image has to be segmented using the well-known semiautomatic intelligent scissor method proposed by Mortensen and Barrett31  was also calculated, which represents the ratio of the standard deviation to the mean.Statistical analysis was performed using SPSS software version 21 . Continuous variables were expressed as mean ± standard deviation. For paired samples, a P = 0.89, R = 0.78, R2 = 0.60; P = 0.87, R = 0.78, R2 = 0.59; P = 0.99, R = 0.73, R2 = 0.54), respectively. The CVs were 3.24 ± 1.54%, 3.80 ± 1.70%, and 3.27 ± 1.82% for the whole kidney, cortical, and medullary perfusions on session 1 and 2.30 ± 0.95%, 3.02 ± 1.21%, and 3.87 ± 2.07% on session 2, respectively. The corresponding intraclass correlations (ICCs) were 0.93, 0.95, and 0.94 on session 1 and 0.97, 0.96, and 0.92 on session 2, respectively.Mean perfusion of the whole kidney was 307.26 ± 25.65 mL/min/100 g, mean cortical perfusion was 337.10 ± 34.83 mL/min/100 g, and mean medullary perfusion was 279.61 ± 26.73 mL/min/100 g. Mean perfusion on session 1 was 307.08 ± 26.91 mL/min/100 g for the whole kidney, 336.79 ± 36.54 mL/min/100 g for the cortex, and 279.60 ± 27.81 mL/min/100 g for the medulla. On session 2 the corresponding perfusion results were 307.45 ± 24.65, 337.41 ± 33.48, and 279.61 ± 25.94 mL/min/100 g (P > 0.05) and showed a very good correlation (R = 0.86/0.87/0.81). The results of kidney perfusion measurements are shown in Figure The total ICC for cortical perfusion was 0.97, while the CV was 4.19% ± 1.33%. The ICC for medullary perfusion was 0.96, while the CV was 4.12% ± 1.36%. The ICC for the whole kidney perfusion was 0.97, while the CV was 3.43% ± 0.86%. Measurements did not differ significantly , which therefore enables dynamic renal perfusion measurements during therapeutic intervention. This method provides a distinct advantage over PAH and gadolinium contrast-enhanced MRI, which are not repeatable within such a short time frame. The relatively short scan time and the noninvasive character of ASL are also of benefit during recruitment and examination in the context of clinical studies.Currently, the PAH clearance method is the gold standard to assess renal plasma flow in humans from which the renal blood flow can be determined by a scaling factor dependent on the hematocrit. This technique is time-consuming, with the protocol lasting up to 2 hours.34 This disparity may represent physiological or population differences. There are other factors that may also affect the ASL method and potentially contribute to these differences. Varying ASL protocols have been employed, differing in breathing technique, field strength, and motion correction, using both single and multislice approaches.38 The lack of standardization is a constraint regarding the practice of ASL in clinical routine. ASL appeared to be suitable for quantitative kidney perfusion measurements in patients with renal artery stenosis, as ASL data were related with renal artery stenosis grade and single photon emission CT (SPECT) perfusion values in a cohort of 12 patients with renal artery stenosis, as well as 6 patients with arterial hypertension without renal artery stenosis.17 In a recent study, a qualitative agreement between ASL and scintigraphy with respect to kidney perfusion measurements was found.21 Another study demonstrated a significant increase in renal perfusion quantified with ASL, using the renin inhibitor aliskiren.39 The same group has shown that renal denervation performed in patients with drug-resistant hypertension does not appear to impact renal perfusion, again assessed with ASL.40 These data suggest that ASL is a promising method for the assessment of renal hemodynamic changes during therapeutic interventions, without the need for more time-consuming methods, the administration of exogenous contrast agents or the use or ionizing radiation. ASL may potentially provide substantial insights into the pathophysiology of a number of conditions in which renal perfusion is affected, including acute kidney injury, heart failure, and renal arterial disease.43 Kidney perfusion is also of interest in the context of chronic kidney disease, including status after kidney transplantation.33 Furthermore, ASL may add important information during the differentiation of histological subtypes of renal masses.44 Rossi et al45 recently reported that a moderate renal dysfunction leads to a significant change in the distribution of cortical perfusion and to a reduced cortical and medullary perfusion. Previous studies demonstrated that cortical renal perfusion is 3 to 4 times higher compared to medullary perfusion.17 Interestingly, our data show a distinctively smaller difference. One explanation for the high perfusion values of the medulla may be attributable to the segmentation since we focused on the correct segmentation of the cortex. Not including parts of the medulla in the segmentation of the cortex was of particular importance. Therefore, the segmentation of the medulla may contain parts of the cortex what explains higher than expected medullary perfusion values. Additionally, the medulla is not as uniform in its makeup as the cortex. The section defined here as the medulla is a band that contains pyramids as well as interlobar veins and arteries.Recently published data using ASL to measure renal perfusion in subjects with normal renal function vary widely, with values ranging from 197 to 329 mL/min/100 g.46 The major advantages of ASL methodology in comparison to other methods to measure kidney perfusion  are its noninvasive nature and quick performance within a few minutes. Moreover, because of the high correlation and low variance of ASL measurements, only small numbers of patients are required in studies to detect clinically meaningful changes. For example, in a parallel design of 2 groups with 12 subjects each, a 10% change in whole kidney perfusion can readily be detected following a pharmacologic intervention compared to the control group. This exemplary sample size calculation underscores the high reliability of ASL kidney perfusion measurements.It should be acknowledged that MRI-based examinations are limited by the relatively high costs, the partly limited access to scanners , some contraindications , and the potentially reduced convenience and tolerability for patients . In addition to the numerous ASL sequences, various acquisition strategies are applied to minimize the error caused by respiratory motion. Consistent with our approach, other studies have employed breath-holding techniques that minimize respiratory motion, which can prove difficult for participants to comply with. In our study, all of our healthy volunteers were able to comply with an 18-second breath hold; however, this strategy may not be appropriate for handicapped patients. Alternative strategies include prolonged acquisition during free breathing, respiratory triggering, and parallel imaging methods.Nevertheless, ASL kidney perfusion measurements are currently a research tool. Further research and improvements in hard- and software are necessary before it can be implemented into clinical practice. Additionally, future work is required to standardize renal perfusion measurements using ASL.Noninvasive ASL kidney perfusion measurements at 1.5 Tesla MRI combined with operator-independent semiautomatic quantification revealed a high correlation and low variance of cortical, medullary, and whole kidney perfusion in healthy subjects. This method potentially facilitates insights into the pathophysiology of a number of conditions in which renal perfusion is affected and is a promising tool for the assessment of renal hemodynamic changes during therapeutic interventions. Since a healthy cohort was investigated, further research needs to be done to show if the low variance and high correlation can be translated to detect clinically meaningful changes.