Point-of-care end-tidal carbon monoxide reflects severity of hemolysis in sickle cell anemia.
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ABSTRACT:
SUBMITTER: Lal A
PROVIDER: S-EPMC4376621 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
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Point-of-care end-tidal carbon monoxide reflects severity of hemolysis in sickle cell anemia.
Lal Ashutosh A Patterson Lasandra L Goldrich Alisa A Marsh Anne A
Pediatric blood & cancer 20150214 5
Carbon monoxide (CO) production from heme catabolism is increased with hemolysis. A portable end-tidal CO (ETCO) monitor was used to analyze breath samples in 16 children with sickle cell anemia (SCA, 5-14 years). Median (range) ETCO for SCA was 4.35 ppm (1.8-9.7) versus 0.80 ppm (0.2-2.3) for controls (P < 0.001). ETCOc >2.1 ppm provided sensitivity and specificity of 93.8% (69.8-99.8%) for detecting SCA. ETCO correlated with reticulocytosis (P = 0.015) and bilirubin (P = 0.009), and was 32% lo ...[more]
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Project description:Carbon monoxide (CO) at low, non-toxic concentrations has been previously demonstrated to exert anti-inflammatory protection in murine models of sickle cell disease (SCD). However CO delivery by inhalation, CO-hemoglobin infusion or CO-releasing molecules presents problems for daily CO administration. Oral administration of a CO-saturated liquid avoids many of these issues and potentially provides a platform for self-administration to SCD patients. To test if orally-delivered CO could modulate SCD vaso-occlusion and inflammation, a liquid CO formulation (HBI-002) was administered by gavage (10 ml/kg) once-daily to NY1DD and Townes-SS transgenic mouse models of SCD. Baseline CO-hemoglobin (CO-Hb) levels were 1.6% and 1.8% in NY1DD and Townes-SS sickle mice and 0.6% in Townes-AS control mice. CO-Hb levels reached 5.4%, 4.7% and 3.0% within 5 minutes in NY1DD, SS and AS mice respectively after gavage with HBI-002. After ten treatments, each once-daily, hemoglobin levels rose from 5.3g/dL in vehicle-treated Townes-SS mice to 6.3g/dL in HBI-002-treated. Similarly, red blood cell (RBC) counts rose from 2.36 x 106/?L in vehicle-treated SS mice to 2.89 x 106/?L in HBI-002-treated mice. In concordance with these findings, hematocrits rose from 26.3% in vehicle-treated mice to 30.0% in HBI-002-treated mice. Reticulocyte counts were not significantly different between vehicle and HBI-002-treated SS mice implying less hemolysis and not an increase in RBC production. White blood cell counts decreased from 29.1 x 103/?L in vehicle-treated versus 20.3 x 103/?L in HBI-002-treated SS mice. Townes-SS mice treated with HBI-002 had markedly increased Nrf2 and HO-1 expression and decreased NF-?B activation compared to vehicle-treated mice. These anti-inflammatory effects were examined for the ability of HBI-002 (administered orally once-daily for up to 5 days) to inhibit vaso-occlusion induced by hypoxia-reoxygenation. In NY1DD and Townes-SS sickle mice, HBI-002 decreased microvascular stasis in a duration-dependent manner. Collectively, these findings support HBI-002 as a useful anti-inflammatory agent to treat SCD and warrants further development as a therapeutic.
| S-EPMC6181332 | biostudies-literature
Project description:To identify the role of end-tidal carbon dioxide (EtCO2) monitoring during polysomnography in evaluation of children with obstructive sleep apnea syndrome (OSAS), including the correlation of EtCO2 with other measures of OSAS and prediction of changes in cognition and behavior after adenotonsillectomy.Analysis of screening and endpoint data from the Childhood Adenotonsillectomy Trial, a randomized, controlled, multicenter study comparing early adenotonsillectomy (eAT) to watchful waiting/supportive care (WWSC) in children with OSAS.Multisite clinical referral settings.Children, ages 5.0 to 9.9 y with suspected sleep apnea.eAT or WWSC.Quality EtCO2 waveforms were present for ? 75% of total sleep time (TST) in 876 of 960 (91.3%) screening polysomnograms. Among the 322 children who were randomized, 55 (17%) met pediatric criteria for hypoventilation. The mean TST with EtCO2 > 50 mmHg was modestly correlated with apnea-hypopnea index (AHI) (r = 0.33; P < 0.0001) and with oxygen saturation ? 92% (r = 0.26; P < 0.0001). After adjusting for AHI, obesity, and other factors, EtCO2 > 50 mmHg was higher in African American children than others. The TST with EtCO2 > 50 mmHg decreased significantly more after eAT than WWSC. In adjusted analyses, baseline TST with EtCO2 > 50 mmHg did not predict postoperative changes in cognitive and behavioral measurements.Among children with suspected obstructive sleep apnea syndrome, overnight end-tidal carbon dioxide (EtCO2) levels are weakly to modestly correlated with other polysomnographic indices and therefore provide independent information on hypoventilation. EtCO2 levels improve with adenotonsillectomy but are not as responsive as AHI and do not provide independent prediction of cognitive or behavioral response to surgery.Childhood Adenotonsillectomy Study for Children with OSAS (CHAT). ClinicalTrials.gov Identifier #NCT00560859.
| S-EPMC4813353 | biostudies-literature
Project description:The intensity of hemolytic anemia has been proposed as an independent risk factor for the development of certain clinical complications of sickle cell disease, such as pulmonary hypertension, hypoxemia and cutaneous leg ulceration. A composite variable derived from several individual markers of hemolysis could facilitate studies of the underlying mechanisms of hemolysis. In this study, we assessed the association of hemolysis with outcomes in sickle cell anemia. A hemolytic component was calculated by principal component analysis from reticulocyte count, serum lactate dehydrogenase, aspartate aminotransferase and total bilirubin concentrations in 415 hemoglobin SS patients. Association of this component with direct markers of hemolysis and clinical outcomes was assessed. As primary validation, both plasma red blood cell microparticles and cell-free hemoglobin concentration were higher in the highest hemolytic component quartile compared to the lowest quartile (P?0.0001 for both analyses). The hemolytic component was lower with hydroxyurea therapy, higher hemoglobin F, and alpha-thalassemia (P?0.0005); it was higher with higher systemic pulse pressure, lower oxygen saturation, and greater values for tricuspid regurgitation velocity, left ventricular diastolic dimension and left ventricular mass (all P<0.0001). Two-year follow-up analysis showed that a high hemolytic component was associated with an increased risk of death (hazard ratio, HR 3.44; 95% confidence interval, CI: 1.2-9.5; P=0.02). The hemolytic component reflects direct markers of intravascular hemolysis in patients with sickle cell disease and allows for adjusted analysis of associations between hemolytic severity and clinical outcomes. These results confirm associations between hemolytic rate and pulse pressure, oxygen saturation, increases in Doppler-estimated pulmonary systolic pressures and mortality (Clinicaltrials.gov identifier: NCT00492531).
| S-EPMC3659937 | biostudies-literature
Project description:BACKGROUND:Based on laboratory cardiopulmonary resuscitation (CPR) investigations and limited adult data, the American Heart Association Consensus Statement on CPR Quality recommends titrating CPR performance to achieve end-tidal carbon dioxide (ETCO2) >20?mmHg. AIMS:We prospectively evaluated whether ETCO2?>?20?mmHg during CPR was associated with survival to hospital discharge. METHODS:Children ?37 weeks gestation in Collaborative Pediatric Critical Care Research Network intensive care units with chest compressions for ?1?min and ETCO2 monitoring prior to and during CPR between July 1, 2013 and June 31, 2016 were included. ETCO2 and Utstein-style cardiac arrest data were collected. Multivariable Poisson regression models with robust error estimates were used to estimate relative risk of outcomes. RESULTS:Blinded investigators analyzed ETCO2 waveforms from 43 children. During CPR, the median ETCO2 was 23?mmHg [quartiles, 16 and 28?mmHg], median ventilation rate was 29 breaths/min [quartiles, 24 and 35 breaths/min], and median duration of CPR was 5?min [quartiles, 2 and 16?min]. Return of spontaneous circulation occurred after 71% of CPR events and 37% of patients survived to hospital discharge. For children with mean ETCO2 during CPR?>?20?mmHg, the adjusted relative risk for survival was 0.92 (0.41, 2.08), p?=?0.84. The median mean ETCO2 among children who survived to hospital discharge was 20?mmHg [quartiles; 15, 28?mmHg] versus 23?mmHg [16, 28?mmHg] among non-survivors. CONCLUSION:Mean ETCO2?>?20?mmHg during pediatric in-hospital CPR was not associated with survival to hospital discharge, and ETCO2 was not different in survivors versus non-survivors.
| S-EPMC6258346 | biostudies-literature
Project description:Hemolysis is a key feature of sickle cell anemia (HbSS). Direct quantitation of hemolysis could be used as an objective outcome in clinical trials of new therapeutics for HbSS and would also enable better human studies of the pathogenesis of complications of HbSS that are ostensibly hemolysis-related, such as pulmonary hypertension. However, contemporary human studies in HbSS have used only surrogate markers of hemolysis rather than direct measurements of RBC survival. We directly quantified hemolysis in HbSS by measuring survival of an age cohort of RBCs labeled with a stable isotope, administered orally as 15 N-glycine, a metabolic precursor of heme. The atomic excess of 15 N in heme extracted from blood was monitored by mass spectrometry over time. We performed 13 labeling experiments in 11 individuals with HbSS. Mean RBC survival was 31.9 days (range 14.1-53.6). Both HbF level, a known determinant of hemolysis, and absolute reticulocyte count (ARC), an index of the marrow's response to hemolysis, correlated with directly measured RBC survival (r?=?0.61, P?<?0.002; r?=?-0.84, P?<?0.001). However, commonly used biochemical surrogates of hemolysis (LDH, AST, bilirubin, and plasma free hemoglobin) did not correlate with directly measured RBC survival. These biochemical surrogates should be interpreted cautiously, at best, in clinical trials and human physiologic studies in HbSS. ARC was the best correlate of total hemolysis, but only 70% of the variation in RBC survival was reflected in this marker. If greater accuracy is required in human studies, 15 N-glycine RBC labeling can directly and accurately quantify hemolysis. Am. J. Hematol. 91:1195-1201, 2016. © 2016 Wiley Periodicals, Inc.
| S-EPMC5118160 | biostudies-literature
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| S-EPMC5433739 | biostudies-literature
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| S-EPMC2770753 | biostudies-literature
Project description:BACKGROUND:Intravascular hemolysis in sickle cell anemia could contribute to complications associated with nitric oxide deficiency, advancing age, and increased mortality. We have previously reported that intense hemolysis is associated with increased risk of vascular complications in a small cohort of adults with sickle cell disease. These observations have not been validated in other populations. METHODS:The distribution of serum lactic dehydrogenase (LDH) values was used as a surrogate measure of intravascular hemolysis in a contemporaneous patient group and an historical adult population from the Cooperative Study of Sickle Cell Disease (CSSCD), all with sickle cell anemia. Chronic hyper-hemolysis was defined by the top LDH quartile and was compared to the lowest LDH quartile. RESULTS:Hyper-hemolysis subjects had higher systolic blood pressure, higher prevalence of leg ulcers (OR 3.27, 95% CI 1.92-5.53, P<0.0001), priapism (OR 2.62, 95% CI 1.13-6.90, P = 0.03) and pulmonary hypertension (OR 4.32, 95% CI 2.12-8.60, P<0.0001), while osteonecrosis (OR 0.32, 95% CI 0.19-0.54, P<0.0001) and pain (OR 0.23, 95% CI 0.09-0.55, P = 0.0004) were less prevalent. Hyper-hemolysis was influenced by fetal hemoglobin and alpha thalassemia, and was a risk factor for early death in the CSSCD population (Hazard Ratio = 1.97, P = 0.02). CONCLUSIONS:Steady state LDH measurements can identify a chronic hyper-hemolysis phenotype which includes less frequent vasooclusive pain and earlier mortality. Clinicians should consider sickle cell specific therapies for these patients, as is done for those with more frequent acute pain. The findings also suggest that an important class of disease modifiers in sickle cell anemia affect the rate of hemolysis.
| S-EPMC2330070 | biostudies-literature
Project description:RationalePulmonary arterial hypertension (PAH) is characterized in part by increased dead space ventilation, which can be estimated noninvasively at the bedside by measurement of end-tidal CO2 (ETco2).ObjectivesPrior work has demonstrated that ETco2 is lower in patients with PAH than in control patients, but whether ETco2 has prognostic value is unknown. We hypothesized that lower measurements of ETco2 in patients with PAH correlate with worse long-term outcomes.MethodsPatients with PAH seen in our referral clinic were prospectively recruited for ETco2 measurement between September 2009 and February 2010. Vital status as of July 2015 was documented using medical records and the Social Security Death Index.ResultsEighty-two patients were followed for a median of 60 months. Twenty-six patients died, and two were lost to follow-up. Patients who died were more likely to be older (58.5 ± 14.9 vs. 47.6 ± 12.2 yr; P < 0.05) and to have shorter 6-minute walk distance (296 ± 127 vs. 401 ± 92 m; P < 0.05). Mean ETco2 in survivors was 30.5 ± 4.8 mm Hg, whereas mean ETco2 in patients who died was 27.1 ± 4.2 mm Hg (P = 0.004). After stratification by median baseline ETco2 of 29 mm Hg, survival in each group was analyzed. Patients with lower ETco2 had shorter survival (P = 0.006). Cox regression analysis with ETco2 as a continuous variable revealed the hazard ratio to be 0.88 (95% confidence interval, 0.80-0.97; P = 0.006). In 52 patients with more than one measurement a median of 17 months apart, ETco2 was unchanged.ConclusionsOur single-center data suggest that lower ETco2 is associated with shorter survival and that ETco2 is stable over time in patients with PAH.
| S-EPMC6850742 | biostudies-literature
Project description:PURPOSE:Despite growing evidence supporting the potential benefits of higher end-tidal carbon dioxide (ETCO2) levels in surgical patients, there is still insufficient data to formulate guidelines for ideal intraoperative ETCO2 targets. As it is unclear which intraoperative ETCO2 levels are currently used and whether these levels have changed over time, we investigated the practice pattern using the Multicenter Perioperative Outcomes Group database. METHODS:This retrospective, observational, multicentre study included 317,445 adult patients who received general anesthesia for non-cardiothoracic procedures between January 2008 and September 2016. The primary outcome was a time-weighted average area-under-the-curve (TWA-AUC) for four ETCO2 thresholds (< 28, < 35, < 45, and > 45 mmHg). Additionally, a median ETCO2 was studied. A Kruskal-Wallis test was used to analyse differences between years. Random-effect multivariable logistic regression models were constructed to study variability. RESULTS:Both TWA-AUC and median ETCO2 showed a minimal increase in ETCO2 over time, with a median [interquartile range] ETCO2 of 33 [31.0-35.0] mmHg in 2008 and 35 [33.0-38.0] mmHg in 2016 (P <0.001). A large inter-hospital and inter-provider variability in ETCO2 were observed after adjustment for patient characteristics, ventilation parameters, and intraoperative blood pressure (intraclass correlation coefficient 0.36; 95% confidence interval, 0.18 to 0.58). CONCLUSIONS:Between 2008 and 2016, intraoperative ETCO2 values did not change in a clinically important manner. Interestingly, we found a large inter-hospital and inter-provider variability in ETCO2 throughout the study period, possibly indicating a broad range of tolerance for ETCO2, or a lack of evidence to support a specific targeted range. Clinical outcomes were not assessed in this study and they should be the focus of future research.
| S-EPMC6331507 | biostudies-other