Search

OBJECTIVE: The Calcium for Out-of-hospital Cardiac Arrest (COCA) trial was a randomized, placebo-controlled, double-blind trial of calcium for out-of-hospital cardiac arrest. The primary and secondary outcomes have been reported previously. This article describes the long-term outcomes of the trial.METHODS: Patients aged ≥ 18 years were included if they had a non-traumatic out-of-hospital cardiac arrest during which they received adrenaline. The trial drug consisted of calcium chloride (5 mmol) or saline placebo given after the first dose of adrenaline and again after the second dose of adrenaline for a maximum of two doses. This article presents pre-specified analyses of 6-month and 1-year outcomes for survival, survival with a favorable neurological outcome (modified Rankin Scale of 3 or less), and health-related quality of life.RESULTS: A total of 391 patients were analyzed. At 1 year, 9 patients (4.7%) were alive in the calcium group while 18 (9.1%) were alive in the placebo group (risk ratio 0.51; 95% confidence interval 0.24, 1.09). At 1 year, 7 patients (3.6%) were alive with a favorable neurological outcome in the calcium group while 17 (8.6%) were alive with a favorable neurological outcome in the placebo group (risk ratio 0.42; 95% confidence interval 0.18, 0.97). Outcomes for health-related quality of life likewise suggested harm of calcium but results were imprecise with wide confidence intervals.CONCLUSIONS: Effect estimates remained constant over time suggesting harm of calcium but with wide confidence intervals. The results do not support calcium administration during out-of-hospital cardiac arrest. Trial registration ClinicalTrials.gov-number, NCT04153435.

Importance: It is unclear whether administration of calcium has a beneficial effect in patients with cardiac arrest.Objective: To determine whether administration of calcium during out-of-hospital cardiac arrest improves return of spontaneous circulation in adults.Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial included 397 adult patients with out-of-hospital cardiac arrest and was conducted in the Central Denmark Region between January 20, 2020, and April 15, 2021. The last 90-day follow-up was on July 15, 2021.Interventions: The intervention consisted of up to 2 intravenous or intraosseous doses with 5 mmol of calcium chloride (n = 197) or saline (n = 200). The first dose was administered immediately after the first dose of epinephrine.Main Outcomes and Measures: The primary outcome was sustained return of spontaneous circulation. The secondary outcomes included survival and a favorable neurological outcome (modified Rankin Scale score of 0-3) at 30 days and 90 days.Results: Based on a planned interim analysis of 383 patients, the steering committee stopped the trial early due to concerns about harm in the calcium group. Of 397 adult patients randomized, 391 were included in the analyses (193 in the calcium group and 198 in the saline group; mean age, 68 [SD, 14] years; 114 [29%] were female). There was no loss to follow-up. There were 37 patients (19%) in the calcium group who had sustained return of spontaneous circulation compared with 53 patients (27%) in the saline group (risk ratio, 0.72 [95% CI, 0.49 to 1.03]; risk difference, -7.6% [95% CI, -16% to 0.8%]; P = .09). At 30 days, 10 patients (5.2%) in the calcium group and 18 patients (9.1%) in the saline group were alive (risk ratio, 0.57 [95% CI, 0.27 to 1.18]; risk difference, -3.9% [95% CI, -9.4% to 1.3%]; P = .17). A favorable neurological outcome at 30 days was observed in 7 patients (3.6%) in the calcium group and in 15 patients (7.6%) in the saline group (risk ratio, 0.48 [95% CI, 0.20 to 1.12]; risk difference, -4.0% [95% CI, -8.9% to 0.7%]; P = .12). Among the patients with calcium values measured who had return of spontaneous circulation, 26 (74%) in the calcium group and 1 (2%) in the saline group had hypercalcemia.Conclusions and Relevance: Among adults with out-of-hospital cardiac arrest, treatment with intravenous or intraosseous calcium compared with saline did not significantly improve sustained return of spontaneous circulation. These results do not support the administration of calcium during out-of-hospital cardiac arrest in adults.Trial Registration: ClinicalTrials.gov Identifier: NCT04153435.

PURPOSE: Aim of this study was to evaluate the dynamic changes in renal relative signal intensity (RSI) following the administration of Gd-DTPA in adolescent pigs with complete and partial unilateral ureteric obstruction. METHODS: Pigs were divided into 3 groups: partial and complete unilateral ureteric obstruction and controls. Complete unilateral ureteric obstruction (CUUO) was created by ligating the left ureter, whereas partial unilateral ureteric obstruction (PUUO) was created in pigs of 2 weeks of age by embedding the left ureter into the psoas muscle. Dynamic MRI was performed before and at 0 - 60 min after an intravenous bolus injection of Gd-DTPA. Mean RSI of the renal cortex, medulla and pelvis was measured and interpreted as an indirect measure of the renal function. In addition, renography was performed, and renal morphology was examined IN VITRO. RESULTS: Three phases of RSI were identified. The dynamic RSI patterns differed markedly between obstructed and control kidneys. In PUUO kidneys, Phase 1 of the mean RSI of the cortex and medulla demonstrated a decreased amplitude and prolonged duration, whereas in Phase 2 the mean RSI of the pelvis was increased. In acute CUUO kidneys, the mean RSI patterns were similar to those of controls, except for a significant increase of the pelvic mean RSI. CONCLUSIONS: Gd-DTPA enhanced dynamic MRI allowed a characterization and differentiation of renal function and morphology of normal and obstructed kidneys, and secondly, provided potentially important information on renal concentrative and filtration availability.

Udgivelsesdato: 2008-May-29 PURPOSE: We investigated the functional consequences of relieving ureteric obstruction in young pigs with experimental hydronephrosis (HN) induced by partial unilateral ureteropelvic obstruction. MATERIALS AND METHODS: Three groups of animals were followed from the age of 2 weeks to the age of 14 weeks: Eight animals had severe or grades 3-4 HN throughout the study. Six animals had relief of the obstruction after 4 weeks. Six animals received sham operations at both ages. Morphological and functional examinations were performed at age 6 weeks and again at age 14 weeks and consisted of magnetic resonance imaging (MRI), technetium-diethylenetriaminepentaaceticacid ((99m)Tc-DTPA) renography, renal technetium-dimercaptosuccinicacid ((99m)Tc-DMSA) scintigraphy, and glomerular filtration rate (GFR) measurement. RESULTS: After relief of the partial obstruction, there was reduction of the pelvic diameter and improvement of urinary drainage. Global and relative kidney function was not significantly affected by either obstruction or its relief. Renal (99m)Tc-DMSA scintigraphy showed a change in both the appearance of the kidney and a change in the distribution within kidneys even after relief of obstruction. CONCLUSION: This study shows that partial ureteric obstruction in young pigs may be associated with little effect on global and differential kidney function. However, even after relief of HN, the distribution of (99m)Tc-DMSA in the kidney remains abnormal suggesting that a normal differential renal function may not represent a normal kidney.

Purpose To evaluate the current literature to see if the published results of MRI-glomerular filtration rate (GFR) stand up to the claim that MRI-GFR may be used in clinical practice. Claims in the current literature that Gadolinium (Gd) DTPA dynamic contrast enhanced (DCE) MRI clearance provides a reliable estimate of glomerular filtration are an overoptimistic interpretation of the results obtained. Before calculating absolute GFR from Gd-enhanced MRI, numerous variables must be considered. Materials and Methods We examine the methodology in the published studies on absolute quantification of MRI-GFR. The techniques evaluated included the dose and volume of Gd-DTPA used, the speed of injection, acquisition sequences, orientation of the subject, re-processing, conversion of signal to concentration and the model used for analysis of the data as well as the MRI platform. Results Claims in the current literature that using DCE MRI “Gd DTPA clearance provides a good estimate of glomerular filtration” are not supported by the data presented and a more accurate conclusion should be that “no MRI approach used provides a wholly satisfactory measure of renal GFR function.” Conclusion This study suggests that DCE MRI-GFR results are not yet able to be used as a routine clinical or research tool. The published literature does not show what change in DCE MRI-GFR is clinically significant, nor do the results in the literature allow a single DCE MRI-GFR measurement to be correlated directly with a multiple blood sampling technique. J. Magn. Reson. Imaging 2008. © 2008 Wiley-Liss, Inc.

Udgivelsesdato: 2008-Jan BACKGROUND: Congenital obstructive renal disease often requires a decision early in the child's life on whether or not surgery is required. Differential renal function (DRF) calculated from the renogram provides important information for the correct decision in this process. A recent publication cast doubt as to the reliability of the renogram in providing DRF in the young child. AIM: To describe the day-to-day variation and reproducibility of the two commonly used agents for estimating DRF. METHODS: Within 1 week, 4-week-old pigs each underwent three examinations with both 99mTc-DTPA and 99mTc-DMSA. DRF values from the 99mTc-DTPA renograms were calculated using both the area under the curve (AUC) and the Rutland-Patlak equation. Day-to-day variations in the results using different background subtraction methods were analysed using the coefficient of variation for each case and the repeatability coefficient for each type of background subtraction. RESULTS: DRF calculated from the 99mTc-DMSA studies showed little variation, with a coefficient of variation of 3.9% in the worst case. The repeatability coefficient calculated from the 99mTc-DTPA studies using the AUC technique combined with the background subtraction method giving the least variation was 14.9% while using the Rutland-Patlak technique with its best background subtraction showed an RC of 9.4%. CONCLUSIONS: The study demonstrates that DRF calculated from 99mTc-DMSA studies have low variability and the results are highly reproducible in immature pigs. The DRF calculated from 99mTc-DTPA renograms failed to show acceptable reproducibility when analysed using either the AUC method or the Rutland-Patlak equation.

Background The objective was to investigate the association between renal structural parameters and renal function. The structural parameters were renal cortical volume, total renal volume, number of glomeruli, and total glomerular volume, and renal function was expressed by the single kidney GFR (skGFR). Investigations were performed using both healthy and chronically diseased kidneys. We investigated which of the structural parameters showed the best correlation to renal function and evaluated the possibility of predicting the renal function from structural parameters. Methods Twenty-four pigs, twelve with healthy kidneys and twelve with diseased kidneys, underwent skGFR measurements. Nephrectomies were performed and structural parameters were estimated using stereological procedures. The correlation between the structural parameters and skGFR was analysed by Pearson's correlation test. The prediction of skGFR from structural parameters was analysed by a linear regression test. Results In general, we demonstrated a good correlation between structural parameters and skGFR. When all kidneys were evaluated together Pearson's correlation coefficient between skGFR and any stereological parameter was above 0.60 and highly significant (p < 0.001), and with r-values ranging from 0.62 regarding number of glomeruli, to 0.78 regarding cortical volume. The best correlation was found between cortical volume and skGFR. Prediction of single kidney GFR from any structural parameter showed to be quite imprecise. Conclusion The observed correlations between structural parameters and renal function suggest that these parameters may potentially be useful as surrogate markers of the renal function. At present, however, precise prediction of renal function based on a single structural parameter seems hard to obtain.

Purpose First, to measure renal cortical volume (Vc) using different MRI methods combined with a semiautomatic segmentation method. Second, to compare MRI measurements of Vc using the semiautomatic segmentation method with a manual segmentation method. Third, to evaluate the reproducibility of Vc measurements. Materials and Methods A total of 22 pigs, 13 with healthy kidneys and nine with diseased kidneys, underwent MRI with two non-contrast-agent methods (MRI100×900 and MRI300×1100) and one contrast-agent method (MRIGd). For each of these methods, Vc was estimated using semiautomatic (Vc100×900, Vc300×1100, and VcGd), as well as manual (VcMANUAL) segmentation. Reference volumes were estimated by stereological means (VcSTEREOLOGY). MRI-derived volumes were compared with reference volumes using a two-tailed paired t-test, and variances between methods were visualized with Bland Altman plots. Reproducibilities were analyzed using covariance analysis. Results Neither measurements of Vc100×900, Vc300×1100, nor VcGd differed markedly from VcSTEREOLOGY using semiautomatic segmentation. Vc was comparable when semiautomatic and manual segmentations were performed at the same scan. Reproducibility of MRI estimated Vc values offered intra- and interindividual differences

Validation of quantitative BOLD MRI measurements in kidney: Application to unilateral ureteral obstruction. Background Blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) provides a measure of deoxyhemoglobin content and therefore an indirect measure of the partial oxygen pressure (pO 2 ). The main purpose of this study was to examine the relationship between the apparent relaxation rate (R2*) in the pig kidney by BOLD imaging and renal tissue pO 2 levels measured directly by oxygen-sensitive microelectrodes. Second, BOLD imaging was applied to kidneys in pigs subjected to acute unilateral ureteral obstruction (UUO) to examine whether this condition is associated with changes in intrarenal oxygenation. Methods Oxygen-sensitive microelectrodes were inserted in the cortex and medulla of pig kidneys ( N = 6). Different arterial and intrarenal levels of pO 2 were obtained by stepwise changing the oxygen-to-nitrogen ratio supplied by a respirator. Simultaneous BOLD MRI measurements using an R2*-sensitive Echo Planar Imaging (EPI) sequence were performed on the contralateral kidney. In another group of pigs ( N = 3) BOLD imaging was performed following 24 hours of UUO. Results When the inhaled oxygen fraction was 5% to 70%, R2* was linearly related to pO 2 levels (cortex ΔR2*/ΔpO 2 =-1.2 ms −1 kPa −1 , and medulla ΔR2*/ΔpO2 =–1.7 ms −1 kPa −1 ). Twenty-four hours of UUO was associated with an increased R2* in the cortex and a decreased R2* in medulla as compared with baseline, which remained augmented after the release of UUO, indicating that pO 2 levels were reduced in the cortex and increased in the medulla during and after release of obstruction. Conclusion BOLD MRI provides noninvasive estimates of regional renal oxygen content and our study demonstrates that this technique may provide a useful tool in UUO which is associated with altered renal oxygen consumption.

PURPOSE: We evaluated the effects of norepinephrine on transport pressures in the normal upper urinary tract of the pig during increasing perfusion rates.MATERIALS AND METHODS: Anesthetized Danish landrace Yorkshire pigs weighing 38 to 40 kg were studied. Transparenchymally 2, 6Fr catheters were introduced into the left renal pelvis for pressure measurements and perfusion, respectively. An ultrasonic flow probe was inserted around the left renal artery to record blood flow. A 10Fr catheter was placed transurethrally for bladder drainage and the bladder was maintained empty during the entire study. In the 5 group 1 pigs the pelvic pressure increase was examined at increasing perfusion rates of the renal pelvis (2, 4, 6, 8, 10 and 15 ml per minute) in response to endoluminal administration of increasing concentrations of norepinephrine (0, 5, 50 and 100 microg/ml) in saline. In the 5 group 2 pigs the pressure flow study was also done 4 times per animal using isotonic saline.RESULTS: Endoluminal norepinephrine had a dose dependent effect on the pressure flow relationship. Perfusion with 5 and 50 microg/ml norepinephrine caused a delayed increase and a decrease in pelvic pressure in response to increasing flow rates, whereas perfusion with 100 microg/ml norepinephrine significantly inhibited and almost eliminated the pressure increase at all perfusion rates compared with saline perfusion. Importantly there were no changes in blood pressure, the heart rate or renal arterial blood flow. In group 2 perfusion with isotonic saline resulted in the same pressure response to increasing flow rates each time.CONCLUSIONS: Endoluminal administration of norepinephrine caused a dose dependent inhibition on the pressure phases of the pressure flow relationship of the upper urinary tract in pigs. No systemic changes were observed. These observations may provide a useful adjuvant treatment strategy for upper urinary tract stone treatment and endoscopy.

Purpose: To study the quantitative effects of vitrectomy on fluorescein transport kinetics across the ocular barriers. Methods: Thirty-six domestic swine were used in this study. Twenty anesthetized swine were given a standardized fluorescein intravenous injection immediately after unilateral vitrectomy. This was followed by one single central sample aspiration from the vitreous and the anterior chamber of both eyes in individual animals at increasing intervals up to 24 h after the injection. Fluorescein concentrations in the samples were determined by high-pressure liquid chromatography (HPLC). Eight swine underwent unilateral vitrectomy followed by anterior chamber and vitreous fluorophotometry on both eyes 1 month later. The fluorescein concentrations determined using this method were followed for 24 h. Similar examinations were performed in a control group of eight swine that did not undergo vitrectomy. Anterior chamber, vitreous, and plasma fluorescein concentration/time courses were analyzed kinetically by iterative nonlinear regression analysis. Results: The barrier surrounding the anterior chamber of the eye was immediately impaired after vitrectomy, as evidenced by an increased area under the fluorescein concentration versus time curve, but the transport kinetics were restored within 1 month after surgery. The blood-retinal barrier was, however, persistently altered following vitrectomy. Transport rate and extent of drug penetration into the vitreous were increased, while drug elimination from the vitreous remained unchanged. Conclusion: Vitrectomy led to persistent kinetic fluorescein transport changes in the blood-retinal barrier resulting in faster and increased drug penetration to the vitreous, whereas similar alterations in the anterior chamber barrier transport were only transitory.

Purpose Congenital obstructive renal disease often requires a decision very early in the patients’ life on whether or not surgery is required. Here the renogram provides important information for the correct decision in this process. In our investigations of experimental unilateral ureteropelvic junction obstruction we have used both 99mTc-DTPA and 99mTc-DMSA in young pigs. This study was designed to describe the day to day variations in such investigations. Material and methods Six normal animals each underwent 3 examinations with 99mTc-DTPA and 99mTc-DMSA, respectively, on alternating consecutive days. From all renograms differential renal function (DRF) was calculated using different types of background subtraction. Further, DRF from the 99mTc-DTPA renograms were calculated using both the area under the curve (AUC) and the Rutland-Patlak equation. The data was analysed to asses the variation and their possible origin from biological day-to-day differences. Day-to-day variations in the results of each type of background subtraction were analysed using the coefficient of variation (CV). Results The results did not indicate that biological difference is a source of variation, The DRF calculated from the 99mTc-DMSA studies showed little variation with a CV of 3.92% in the worst case. The 99mTc-DTPA studies showed large variation. The AUC technique with the best background subtraction showed the narrowest variation with a CV of 14.96%. The Rutland-Patlak technique with its’ best background subtraction showed a slight improvement with a CV of 10.89%. Conclusions The study demonstrates that DRF calculated from 99mTc-DMSA studies have limited variability and results are highly reproducible. The DRF calculated from 99mTc-DTPA renograms failed to show acceptable reproducibility when analysed using both AUC and the Rutland-Patlak correction.

Purpose We present a novel MRI technique to measure the renal cortical volume (Vc). This objective is motivated by the fact that renal function is primarily driven by the glomerular function taking place in the renal cortical segment, and thus, shrinkage or growth of renal cortex could become a determinant factor for the kidney function. Material and methods We included 22 adult pigs: 13 healthy and 9 with relieved unilateral ureteral obstruction (UUO). MRI volumetry of both kidneys was performed using two different strategies: one without MR contrast-agent, and one with MR contrast-agent. The acquired images were analysed using both semiautomatic and manual segmentation of the renal cortex, and Vc was calculated. Nephrectomy was subsequently performed and reference values of Vc were estimated by stereology. Results Vc in healthy pigs was estimated quite precisely with both MRI methods as compared with reference values. In UUO kidneys, the non-contrast MRI method gave Vc values comparable to those found by stereological means, whereas contrast-agent MRI method overestimated Vc slightly. Second, we found that semiautomatic and manual segmentation resulted in almost similar Vc values. Reproducibility of estimated cortical volumes offered both intra- and interindividual differences below 5%. Conclusions We found that MRI volumetry of renal cortex can be performed with high precision and high reproducibility. This study presents a novel non-contrast-agent MRI method that allows accurate estimation of Vc, both in healthy and diseased animals. We believe that it could become a supplementary tool to daily invasive measures in kidneys.

Udgivelsesdato: Dec PURPOSE: We examined effects on kidney function and morphology of a partial ureteropelvic junction obstruction induced late in the postnatal nephrogenesis period of the pig. We compared the results to a similar study on pigs with obstruction induced early in the nephrogenesis period. MATERIALS AND METHODS: A total of 20 14-day-old pigs were included in the study. Fifteen animals were randomized to partial unilateral obstruction and 5 were sham operated. Kidney function and morphology were analyzed regarding glomerular filtration rate, renographic functional share and total kidney volume at the age of 4, 12 and 24 weeks. RESULTS: At age 4 weeks hydronephrosis was found in all obstructed kidneys included in the study. Four obstructed kidneys had renographic functional share 40% or greater and 1 deteriorated to less than 40% at 24 weeks. A total of 11 obstructed kidneys had a functional share less than 40%, 5 increased to a share greater than 40% at age 24 weeks and 3 had decreasing share from age 4 to 24 weeks. Single kidney glomerular filtration rate of the contralateral kidneys was significantly increased at all ages. Volume of the contralateral kidney was significantly increased at age 4 and 12 weeks. CONCLUSIONS: The variability and course of renographic functional share in kidneys subjected to partial obstruction at age 2 weeks was similar to findings obtained in pigs obstructed at age 2 days. In contrast to these our study showed compensatory increase in function and size of the contralateral kidney, suggesting that contralateral compensation is an ability gained late in the nephrogenesis period.