Intravenous vs. intraosseous vascular access during out-of-hospital cardiac arrest - protocol for a randomised clinical trial.

Objective: During cardiac arrest, current guidelines recommend attempting intravenous access first and to consider intraosseous access if intravenous access is unsuccessful or impossible. However, these recommendations are only based on very low-certainty evidence. Therefore, the "Intravenous vs Intraosseous Vascular Access During Out-of-Hospital Cardiac Arrest" (IVIO) trial aims to determine whether there is a difference in patient outcomes depending on the type of vascular access attempted during out-of-hospital cardiac arrest. This current article describes the clinical IVIO trial. Methods: The IVIO trial is an investigator-initiated, randomised trial of intravenous vs. intraosseous vascular access during adult non-traumatic out-of-hospital cardiac arrest in Denmark. The intervention will consist of minimum two attempts (if unsuccessful on the first attempt) to successfully establish intravenous or intraosseous vascular access during cardiac arrest. The intraosseous group will be further randomised to the humeral or tibial site. The primary outcome is sustained return of spontaneous circulation and key secondary outcomes include survival and survival with a favourable neurological outcome at 30 days. A total of 1,470 patients will be included. Results: The trial started in March 2022 and the last patient is anticipated to be included in the spring of 2024. The primary results will be reported after 90-day follow-up and are anticipated in mid-2024. Conclusion: The current article describes the design of the Danish IVIO trial. The findings of this trial will help inform future guidelines for selecting the optimal vascular access route during out-of-hospital cardiac arrest.

Effect of calcium vs. placebo on long-term outcomes in patients with out-of-hospital cardiac arrest.

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.

Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

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.

The association between renal function and structural parameters: a pig study.

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.

Normal differential renal function does not indicate a normal kidney after partial ureteropelvic obstruction and subsequent relief in 2-week-old piglets.

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.

Reproducibility and repeatability of differential renal function in 4-week-old piglets.

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.

Different strategies for MRI measurements of renal cortical volume.

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 (MRI 100 x 900 and MRI 300 x 1100) and one contrast-agent method (MRI Gd). For each of these methods, Vc was estimated using semiautomatic (Vc(100 x 900), Vc(300 x 1100), and Vc(Gd)), as well as manual (Vc MANUAL) segmentation. Reference volumes were estimated by stereological means (Vc STEREOLOGY). 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 Vc 100 x 900, Vc 300 x 1100, nor Vc Gd differed markedly from Vc STEREOLOGY 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 <5%. CONCLUSION: Vc can in both healthy and diseased kidneys be measured accurately with MRI using both semiautomatic and manual segmentation, and measurements can be obtained with a high reproducibility. Measurements of Vc 100 x 900 may in the future become suitable in patients with chronic renal failure.

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 DeltaR2*/DeltapO(2)=-1.2 ms(-1)kPa(-1), and medulla DeltaR2*/DeltapO2 =-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.