2 Minute Medicine Rewind August 1, 2022

Endotracheal Tube Size in Critically Ill Patients

1. This retrospective study reports that in critically ill patients, there was no significant difference in 30-day all cause death between patients who received a small-for-size endotracheal tube (ETT), an appropriate-for-size ETT, or a large-for-size ETT.

Evidence Rating Level: 2 (Good)

Tracheal intubation can be a life-saving procedure in critically ill patients, and up to 57% of these patients that are intubated for longer than 12 hours develop mucosal injury in their proximal airway, which is linked to dyspnea for a prolonged period after extubation. Previous studies have found an association with large ETT size and risk. With endotracheal intubation, patient height is the primary determinant for airway size, but it is important to note there are no clear guidelines surrounding the selection of ETT. There is a historical belief that smaller ETTs may impair acute recovery from illness, but it has been found that almost 1 in 4 patients are intubated with an inappropriately large ETT. This retrospective study aimed to investigate the use of smaller and larger ETTs and the on outcomes in critically ill patients. 814 patients were included in the final analysis who underwent endotracheal intubation in the emergency department (ED) or ICU and received at least 12 hours of mechanical intubation at a single academic medical center from June 2020 to November 2020. ETT sizes were categorized into small, appropriate, or large based on patient height. There were no significant differences found in 30-day all-cause in-hospital mortality, which was the primary endpoint of this study. With respect to secondary endpoints, patients with a small ETT had a longer duration of intubation, but otherwise there were no significant differences in terms of secondary outcomes. Furthermore, there was no significant difference in 30-day all-cause in-hospital mortality between patients who received a large and appropriately sized ETT, and there were no significant differences in secondary endpoints as well. Lastly, between the large and small ETT groups, there were no significant differences in 30-day all-cause in-hospital mortality. However, with respect to secondary outcomes, patients with small ETTs had a longer duration of intubation, and increased rates of percutaneous endoscopic gastrotomy (PEG) tube placement when compared to large ETTs. Otherwise, there were no significant differences with respect to other secondary endpoints. Overall, contrary to existing beliefs, the findings of this study suggests that smaller ETTs may not impair illness recovery, and that larger ETTs may not confer any significant benefit. Given that no clear guidelines currently exist for ETT size selection, this study serves as an excellent first step towards developing an approach for using the optimal ETT size. A limitation of this study was that overall illness severity and tube exchange events were not considered, which may be confounding factors when consider ETT size choice.

Association between CYP metabolizer phenotypes and selective serotonin reuptake inhibitors induced weight gain: a retrospective cohort study

1. In this retrospective cohort study, in patients prescribed citalopram, poor/intermediate CYP2C19 metabolizers experienced significantly greater weight gain at 6 months after starting citalopram when compared to normal and rapid/ultrarapid metabolizers.

Evidence Rating Level: 2 (Good)

Obesity and depression are closely related such that patients with obesity have a 55% increased risk of being diagnosed with depression, and patients with depression have a 58% increased risk of developing obesity. Unfortunately, a side effect of selective serotonin reuptake inhibitors, which is the first-line treatment for depression, includes weight gain. Genetic variations between individuals is a factor that can alter the medication’s efficacy, in particular variation of the cytochrome P450 (CYP) enzymes. Interestingly, dosing guidelines have been developed for certain metabolizer phenotypes. Previous research has found an association between genetic variants of obesity and treatment response of SSRIs in depression, but further investigation into pharmacogenomics and weight gain is warranted. This retrospective cohort study aims to study the association between metabolizer phenotype and weight gain in patients prescribed with SSRIs. 663 patients were included in the final analysis, which included patients from the Right Drug, Right Dose, Right Time (RIGHT) Study recruited from 2004 to 2018 who previously underwent genetic sequencing. The three CYP enzymes that were studied were CYP2C19, CYP2D6, and CYP2C9, and patients were categorized into poor/intermediate, normal, and rapid/ultrarapid metabolizers. The total body weight gain percentage (TBWG%) at 6 months for patients who were prescribed an SSRI was 0.7%; TBWG% for citalopram was 1.1%, 0.9% for paroxetine, 1.1% for sertraline, and 0.1% for fluoxetine. With respect to CYP enzyme metabolizer status, patients prescribed citalopram who were poor/intermediate CYP2C19 metabolizers gained significantly more weight than normal and rapid/ultrarapid metabolizers (P=.0001). Otherwise, for fluoxetine. paroxetine, and sertraline there was no significant difference in TBWG% when comparing between CYP2D6 metabolizer phenotypes. There was also no significant difference for fluoxetine and sertraline with the CYP2C19 phenotype, and for fluoxetine with the CYP2D6 phenotype. With respect to the effect of metabolizers on TWBG%, poor CYP2C19 metabolizers on citalopram experienced significantly greater weight gain than rapid metabolizers. Otherwise, for the CYP2D6 phenotype, there was no significant effect for paroxetine, fluoxetine, and sertraline. For the CYP2C9 phenotype, there was no significant difference for fluoxetine, and for the CYP2C19 phenotype, there was no significant difference for fluoxetine and sertraline. Overall, 6 months after prescribing citalopram, patients with a poor/intermediate metabolizer status of CYP2C19 experienced 1.7% more weight gain than normal metabolizers. These findings may have a role in guiding future management decisions surrounding the choice of first-line SSRI in patients with certain risk factors, and demonstrates the importance of pharmacogenomics, especially when considering adverse effects. A major limitation of this study is the small sample size for certain metabolizer phenotypes, which may cause type II error when analyzing outcomes.

Association Between Early Left Ventricular Ejection Fraction Improvement After Transcatheter Aortic Valve Replacement and 5-Year Clinical Outcomes

1. In this retrospective cohort study, left ventricular ejection fraction (LVEF) improvement at 30 days and 1 year was linked with lower 5-year all cause death in patients with severe aortic stenosis (AS) and known left ventricular (LV) dysfunction treated with transcatheter aortic valve replacement (TAVR).

Evidence Rating Level: 2 (Good)

In patients with symptomatic severe aortic stenosis, TAVR is a safe and effective treatment, including those with left ventricular systolic dysfunction. TAVR has been previously found to improve LV ejection fraction by 30 days in approximately half of the patients studied. Failure to improve LVEF has been reported to be linked to an increased risk of 1-year mortality and rehospitalization after TAVR, but these previous studies were quite limited, and the association with LVEF improvement and outcomes remains controversial. This retrospective cohort study collected data from patients at high or intermediate surgical risk in the Placement of Aortic Transcatheter Valves (PARTNER) 1, 2, and S3 trials between July 2007 and April 2015. 659 patients with symptomatic severe AS at high or intermediate surgical risk with a baseline LVEF < 50% that underwent a transfemoral TAVR were included in the study. LVEF was found to improve by 10% points of greater at 30 days post TAVR in 216 patients (32.8%). With respect to the primary outcome, all-cause death within 5 days was lower in patients with early LVEF improvement (P=.04). Specifically, patients with LVEF improvement had a significantly decreased rate of cardiac death (P=.05), but similar rates of noncardiac death and rehospitalization. In addition, LVEF improvement at 1 year was linked with significantly lower 5-year all-cause death, cardiac death, all-cause death or rehospitalization, and cardiac death or rehospitalization. With respect to other secondary outcomes, there was no significant difference between patients with and without LVEF improvement in NYHA functional class or Kansas City Cardiomyopathy Questionnaire (KCCQ). Interestingly, in subgroup analyses, a significant interaction by sex was reported such that early LVEF improvement was linked with significantly improved outcomes in females but not in males. Overall, this study reports that LVEF improvement at 30 days and at 1 year are linked with significantly lower 5-year all cause death.  Further studies into the association of certain risk factors with mortality may be imperative to guide management decisions of severe AS with LV dysfunction in the future. Unfortunately, limitations of this study include exclusion of certain population groups from the original database, including those with severe LV dysfunction (LVEF<20%), as well as unknown etiology of LVEF; patients with LV dysfunction due to causes other than valvular heart disease may not experience LVEF improvement after treatment of AS.

Effect of a Comprehensive Telehealth Intervention vs Telemonitoring and Care Coordination in Patients With Persistently Poor Type 2 Diabetes Control Evidence Rating Level: A Randomized Clinical Trial

1. In this randomized controlled trial, a comprehensive telehealth intervention was linked to a greater improvement in HbA1c% level at 12 months follow up in patients with persistently poorly controlled diabetes (PPDM) when compared to a simpler telehealth model.

2. In patients with PPDM, comprehensive telehealth intervention when compared to a simpler telehealth model was associated with greater improvement in diabetes distress, diabetes self-care, and self-efficacy, but was no associated with greater improvement in depressive symptoms or BMI.

Evidence Rating Level: 1 (Excellent)

Persistently poorly controlled diabetes is defined as HbA1C greater than 8.5% despite receiving clinic-based type 2 diabetes (T2DM) care. Drivers of PPDM include unavailable blood glucose data, medication non-adherence, suboptimal diet or activity, complex medication regimen, and depression, which are factors that are challenging to address in clinic. Given that PPDM is associated with disproportionately negative outcomes, it is important to consider optimal care delivery for this patient population. Telehealth has been found previously to improve outcomes in PPDM, but there is inconsistent data with respect to multicomponent T2D interventions. This randomized controlled trial compared the effect of a comprehensive telehealth intervention and a simpler telehealth approach on patient HbA1c level. Patients were randomized to receive either a comprehensive telehealth intervention, which consisted of an extensive multidisciplinary team including multiple nurses, diabetes physicians, and psychiatry based on issues that needed to be addressed for individual patients, or a simpler telehealth approach with telemonitoring and care coordination. 200 patients recruited from December 2018 to January 2020 in 2 Veterans Affairs healthcare systems were randomized to either the comprehensive telehealth intervention or the simple telehealth group. The primary outcome was patient HbA1c level, and secondary outcomes included diabetes distress, diabetes self-care, self-efficacy, BMI, and depression symptoms. After one year of follow up, the estimated difference of HbA1c change between the two groups was -0.61%, which was statistically significant favouring comprehensive telehealth (P=.02). With respect to secondary outcomes, the comprehensive telehealth group resulted in greater improvement in diabetes distress, diabetes self-care, and self-efficacy, while there was no statistically significant difference in depressive symptoms at 12 months or BMI at 6 months following initiation of the interventions. With respect to limitations, the results may have limited generalizability to healthcare systems that do not have funding or capacity for telehealth, especially in the comprehensive interventions group. Overall, this article suggests that a comprehensive telehealth approach is associated with a greater improvement in HbA1c level. With the rise of telehealth following the COVID-19 pandemic, reassessment of care delivery systems will be important to determine optimal management of PPDM going forwards.

Demographic and Regional Trends of Heart Failure-Related Mortality in Young Adults in the US, 1999-2019

1. In this retrospective cohort analysis, heart failure (HF) related mortality has increased in young adults between 1999 and 2019.

2. There exists significant demographic trends in HF-related mortality in young adults; in particular, men were found to have a significantly higher mortality rate than women, and Black adults were found to have a significantly higher mortality rate than White and Hispanic adults.

Evidence Rating Level: 2 (Good)

Heart failure is mostly diagnosed in older adults, but there has been an increase in the proportion of young adults diagnosed with HF in recent years. This may be related to the rising burden of cardiometabolic risk factors beginning at a younger age. There exists limited data surrounding HF-related mortality in younger adults, and it is important to characterize this issue to guide future health policy measures. This study aims to investigate demographic and regional trends of HF-related mortality in young adults. Data was extracted from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) from January 1999 to December 2019, and young adults, defined as being aged from 15 to 44, with HF as a contributing or underlying cause of death were included in the study. Crude mortality rates were determined by dividing number of HF-related deaths by the US population of that year, and age-adjusted mortality rates (AAMR) were calculated by standardizing the HF-related deaths to the 2000 US population. In total, 61729 HF-related deaths occurred in young adults in the United States. With respect to individual groups, AAMR was significantly higher in men compared to women (P<.05), and threefold higher in Black adults compared to Hispanic and White adults (P<.05). Overall, the AAMR for HF in young adults increased throughout the study duration, for both men and women, and in all race and ethnicity groups as well. This increase was Black adults had the highest increase in AAMR, followed by Hispanic and White adults. With respect to geographic trends, states in the top 10^th percentile of HF-related mortality had a significantly higher mortality burden than those in the bottom 10^th percentile. Overall, this study reports an increase in HF-related mortality in young adults in recent years and explores the demographic and regional patterns of this increase. Black adults were reported to have an increased AAMR compared to White and Hispanic adults, and significant geographic differences were reported as well. It is imperative to characterize patterns of HF-related mortality so possible contributing factors that results in variability of healthcare can be identified, and so that health policies can be developed to address these discrepancies. In terms of limitations, the increase in electronic health record use may contribute to the increase in reported HF-related mortality in recent years. In addition, further characterization of socioeconomic status of patients as well as other possible contributing factors would be ideal to identify specific risk factors.

Image: PD

©2022 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.