Indexing haemodynamic variables in young children.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Haemodynamic studies in children are rare and most studies have included few subjects in the youngest age group. Haemodynamic variables need to be indexed to establish a reference of normality that is valid in all populations. The traditional way to index haemodynamic variables with body surface area (BSA) is complicated in young children due to its non-linear relationship with body weight (BW). We examined several haemodynamic variables in children by indexing them with BSA and BW. Methods: A single-centre, observational cohort study comparing non-indexed and indexed haemodynamic variables in children undergoing heart surgery (divided into three weight groups: 1-5 kg, >5-10 kg and >10-15 kg). Results: A total of 68 children were included in this study, mean age 11.1 months ± 11.1 month (range 0 to 43 months). All haemodynamic variables, cardiac output (CO), stroke volume (SV), total end-diastolic volume (TEDV), central blood volume (CBV) and active circulation volume (ACV), increased with weight without indexing (P < .05). Indexing variables with BW produced a more linear relationship for all haemodynamic variables between weight groups than BSA. The mean BSA-indexed haemodynamic values were CIBSA 3.5 ± 1.1 L/min/m2 and SVIBSA 27.3 ± 8.9 ml/min/m2 . The mean BW-indexed haemodynamic values were CIBW 180 ± 50 ml/min/kg and SVIBW 1.34 ± 0.38 ml/kg. Blood volume variables indexed with BW were TEDVBW 12.0 ± 2.8 ml/kg, CBVBW 21.3 ± 6.6 ml/kg and ACVBW 70.3 ± 15.2 ml/kg. Conclusions: Indexing haemodynamic variables with BW produces a more appropriate body size-independent scale in young children than BSA. Summary statement: In this study, we studied indexing of haemodynamic variables and estimation of blood volumes in young children undergoing corrective heart surgery using an indicator dilution technology. Keywords: blood volume; body surface area; body weight; cardiac output; children; indexing.Anna & Edwin Berger's Foundation (Lidingo, Sweden) Swedish Children Heart Association (Stockholm, Sweden

Sequence variants in malignant hyperthermia genes in Iceland: classification and actionable findings in a population database.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMalignant hyperthermia (MH) susceptibility is a rare life-threatening disorder that occurs upon exposure to a triggering agent. MH is commonly due to protein-altering variants in RYR1 and CACNA1S. The American College of Medical Genetics and Genomics recommends that when pathogenic and likely pathogenic variants in RYR1 and CACNA1S are incidentally found, they should be reported to the carriers. The detection of actionable variants allows the avoidance of exposure to triggering agents during anesthesia. First, we report a 10-year-old Icelandic proband with a suspected MH event, harboring a heterozygous missense variant NM_000540.2:c.6710G>A r.(6710g>a) p.(Cys2237Tyr) in the RYR1 gene that is likely pathogenic. The variant is private to four individuals within a three-generation family and absent from 62,240 whole-genome sequenced (WGS) Icelanders. Haplotype sharing and WGS revealed that the variant occurred as a somatic mosaicism also present in germline of the proband's paternal grandmother. Second, using a set of 62,240 Icelanders with WGS, we assessed the carrier frequency of actionable pathogenic and likely pathogenic variants in RYR1 and CACNA1S. We observed 13 actionable variants in RYR1, based on ClinVar classifications, carried by 43 Icelanders, and no actionable variant in CACNA1S. One in 1450 Icelanders carries an actionable variant for MH. Extensive sequencing allows for better classification and precise dating of variants, and WGS of a large fraction of the population has led to incidental findings of actionable MH genotypes.deCODE Genetics/Amgen Inc

Indirect Calorimetry Overestimates Oxygen Consumption in Young Children: Caution is Advised Using Direct Fick Method as a Reference Method in Cardiac Output Comparison Studies.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesDirect Fick method is considered a standard reference method for estimation of cardiac output. It relies on indirect calorimetry to measure oxygen consumption. This is important as only a minor measurement error in oxygen consumption can result in false estimation of cardiac output. A number of studies have shown that indirect calorimetry overestimates oxygen consumption in adults. The aim of this prospective single center observational method comparison study was to compare the determination of oxygen consumption by indirect calorimetry and reverse Fick method in pediatric patients. Forty-two children mean age 352 days (range 30 to 1303 days) and mean weight 7.1 kg (range 2.7-13.6 kg) undergoing corrective cardiac surgery were included in the study. The mean (standard deviation) oxygen consumption by reverse Fick method was 43.5 (16.2) ml/min and by indirect calorimetry 49.9 (18.8) ml/min (p < 0.001). Indirect calorimetry overestimated the reverse Fick oxygen consumption by 14.7%. Bias between methods was 6.5 (11.3) ml/min, limits of agreement (LOA) - 15.7 and 28.7 ml/min and percentage error of 47.7%. A significant bias and large percentage error indicates that the methods are not interchangeable. Indirect calorimetry and the direct Fick method should be used with caution as a reference method in cardiac output comparison studies in young children.Swedish Children Heart Association (Stockholm, Sweden) Anna and Edwin Bergers Private Foundation (Lidingo, Sweden

Extracorporeal Arteriovenous Ultrasound Measurement of Cardiac Output in Small Children.

To access publisher's full text version of this article click on the hyperlink belowBackground: Technology for cardiac output (CO) and blood volume measurements has been developed based on blood dilution with a small bolus of physiologic body temperature saline, which, after transcardiopulmonary mixing, is detected with ultrasound sensors attached to an extracorporeal arteriovenous loop using existing central venous and peripheral arterial catheters. This study aims to compare the precision and agreement of this technology to measure cardiac output with a reference method, a perivascular flow probe placed around the aorta, in young children. The null hypothesis is that the methods are equivalent in precision, and there is no bias in the cardiac output measurements. Methods: Forty-three children scheduled for cardiac surgery were included in this prospective single-center comparison study. After corrective cardiac surgery, five consecutive repeated cardiac output measurements were performed simultaneously by both methods. Results: A total of 215 cardiac output measurements were compared in 43 children. The mean age of the children was 354 days (range, 30 to 1,303 days), and the mean weight was 7.1 kg (range, 2.7 to 13.6 kg). The precision assessed as two times the coefficient of error was 3.6% for the ultrasound method and 5.0% for the flow probe. Bias (mean CO ultrasound 1.28 l/min -mean CO flow probe 1.20 l/min) was 0.08 l/min, limits of agreement was +/- 0.32 l/min, and the percentage error was 26.6%. Conclusions: The technology to measure cardiac output with ultrasound detection of blood dilution after a bolus injection of saline yields comparable precision as cardiac output measurements by a periaortic flow probe. The difference in accuracy in the measured cardiac output between the methods can be explained by the coronary blood flow, which is excluded in the cardiac output measurements by the periaortic flow probe.Swedish Children Heart Association, Stockholm, Sweden Anna and Edwin Bergen Foundation, Lidingo, Swede

Sequence variants in malignant hyperthermia genes in Iceland : classification and actionable findings in a population database

Funding Information: The study was funded by deCODE Genetics/Amgen Inc. Publisher Copyright: © 2021, The Author(s).Malignant hyperthermia (MH) susceptibility is a rare life-threatening disorder that occurs upon exposure to a triggering agent. MH is commonly due to protein-altering variants in RYR1 and CACNA1S. The American College of Medical Genetics and Genomics recommends that when pathogenic and likely pathogenic variants in RYR1 and CACNA1S are incidentally found, they should be reported to the carriers. The detection of actionable variants allows the avoidance of exposure to triggering agents during anesthesia. First, we report a 10-year-old Icelandic proband with a suspected MH event, harboring a heterozygous missense variant NM_000540.2:c.6710G>A r.(6710g>a) p.(Cys2237Tyr) in the RYR1 gene that is likely pathogenic. The variant is private to four individuals within a three-generation family and absent from 62,240 whole-genome sequenced (WGS) Icelanders. Haplotype sharing and WGS revealed that the variant occurred as a somatic mosaicism also present in germline of the proband’s paternal grandmother. Second, using a set of 62,240 Icelanders with WGS, we assessed the carrier frequency of actionable pathogenic and likely pathogenic variants in RYR1 and CACNA1S. We observed 13 actionable variants in RYR1, based on ClinVar classifications, carried by 43 Icelanders, and no actionable variant in CACNA1S. One in 1450 Icelanders carries an actionable variant for MH. Extensive sequencing allows for better classification and precise dating of variants, and WGS of a large fraction of the population has led to incidental findings of actionable MH genotypes.Peer reviewe