Value of integrated pulmonary index monitoring for the detection of adverse respiratory events in patients undergoing sedation for gastrointestinal system endoscopy.

Objectives: To determine if the integrated pulmonary index detects changes in ventilation status early in patients undergoing gastrointestinal endoscopy under sedation, and to determine the risk factors affecting hypoxia. METHODS: The retrospective study was conducted at the endoscopy unit of a tertiary university hospital in Turkey and comprised data between October 2018 and December 2019 related to patients of either gender aged >18 years who were assessed as American Society of Anaesthesiologists grade I-III and underwent elective lower and upper gastrointestinal endoscopy. Monitoring was done with capnography in addition to standard procedures. Data was analysed using SPSS 23. RESULTS: Of the 154 patients, 94(%) were females and 60(%) were males. The overall mean age was 50.88±11.8 years (range: 20-70 years). Mean time under anaesthesia was 23.58±4.91 minutes and mean endoscopy time was 21.73±5.06 minutes. During the procedure, hypoxia was observed in 42(27.3%) patients, severe hypoxia in 23(14.9%) and apnoea in 70(45.5%). Mean time between apnoea and hypoxia was 12.59±7.99 seconds, between apnoea and serious hypoxia 21.07±17.64 seconds, between integrated pulmonary index score 1 and hypoxia 12.91±8.17 sec, between integrated pulmonary index score 1 and serious hypoxia 21.59±14.13 seconds, between integrated pulmonary index score <7 and hypoxia 19.63±8.89 seconds, between integrated pulmonary index score <7 and serious hypoxia 28.39±12.66 seconds, between end-tidal carbon dioxide and hypoxia 12.95±8.33 seconds, and between end-tidal carbon dioxide and serious hypoxia 21.29±7.55 seconds. With integrated pulmonary index score 1, sensitivity value for predicting hypoxia and severe hypoxia was 88.1% and 95.7%, respectively, and specificity was 67% and 60.3%, respectively. With integrated pulmonary index score <7, the corresponding values were 100%, 100%, 42% and 64.1%, respectively. CONCLUSIONS: Capnographic monitoring, especially the follow-up integrated pulmonary index score, was found to be valuable and reliable in terms of finding both time and accuracy of the risk factor in the diagnosis of respiratory events.

Assessing hypoxic respiratory failure in mechanically ventilated neonates: A comparative study of oxygen saturation index and oxygenation index.

OBJECTIVE: To investigate the correlation between oxygen saturation index (OSI) and oxygenation index (OI) for evaluating the blood oxygenation status in neonates with respiratory failure requiring mechanical ventilation support and to assess the predictive capability of OSI in determining clinically relevant OI cutoffs. METHODS: A prospective study was conducted on neonates who received invasive mechanical ventilation at the neonatal intensive care unit of tertiary hospital in Vietnam. Bland-Altman analysis was utilized to evaluate the agreement between OSI and OI. RESULTS: A total of 123 neonates, including both term and preterm infants, were included in the study. A high agreement rate of 94.3% within the 95% limits of agreement (between OI and OSI), with a narrow similarity value of 3.3 (95% CI: -5.1 to 11.8) and high correlation coefficient (r = 0.791, p<0.001) was observed. The OSI cut-off value for predicting an OI of >15 was determined to be 7.45, with a sensitivity of 100% and a specificity of 87.4% (AUC 0.955; 95% CI: 0.922-0.989, p < 0.05). Similarly, an OSI cutoff value of 9.9 corresponded to an OI of 25, displaying a sensitivity of 100% and specificity of 87.4% (AUC 0.92). The receiver operating characteristic (ROC) curves for OSI exhibited statistically significant results (p < 0.05). CONCLUSION: The findings demonstrate a strong correlation between OSI and OI in neonates with respiratory failure. Furthermore, OSI, as a non-invasive method, can serve as a substitute for OI to evaluate the severity of hypoxic respiratory failure and lung injury in neonates.

Oxygenation saturation index in neonatal hypoxemic respiratory failure.

BACKGROUND: This study aimed to assess the validity of the oxygenation saturation index (OSI) and the ratio of oxygen saturation to the fraction of inspired oxygen (FIO2) (S/F ratio) with percutaneous oxygen saturation (OSISpO2 and the Sp/F ratio) and to evaluate the correlation between these values and the oxygen index (OI). It also determined their cut-off values for predicting OI in accordance with neonatal hypoxic respiratory failure severity. METHODS: We reviewed the data of 77 neonates (gestational age 31.7 ± 6.1 weeks; birthweight, 1768 ± 983 g) requiring invasive mechanical ventilation between 2013 and 2020, 1233 arterial blood gas samples in total. We calculated the OI, OSISpO2, OSI with arterial oxygen saturation (SaO2) (OSISaO2), Sp/F ratio, and the ratio of SaO2 to FIO2 (Sa/F ratio). RESULTS: The regression and Bland-Altman analysis showed good agreement between OSISpO2 or the Sp/F ratio and OSISaO2 or the Sa/F ratio. Although a significant positive correlation was found between OSISpO2 and OI, OSISpO2 was overestimated in SpO2 > 98% with a higher slope of the fitted regression line than that below 98% of SpO2. Furthermore, receiver-operating characteristic curve analysis using only SpO2 ≤ 98% samples showed that the optimal cut-off points of OSISpO2 and the Sp/F ratio for predicting OI were: OI 5, 3.0 and 332; OI 10, 5.3 and 231; OI 15, 7.7 and 108; OI 20, 11.0 and 149; and OI 25, 17.1 and 103, respectively. CONCLUSION: The cut-off OSISpO2 and Sp/F ratio values could allow continuous monitoring for oxygenation changes in neonates with the potential for wider clinical applications.

The paradox of platypnoea-orthodeoxia syndrome.

Platypnoea-orthodeoxia is a rare clinical syndrome characterised by dyspnoea and oxygen desaturation in the upright position which improves when supine. It requires two components: a sufficiently sized anatomical vascular defect (typically intra-cardiac or intra-pulmonary) combined with a functional component that promotes positional right-to-left shunting. We describe the rare occurrence of a patient with platypnoea-orthodeoxia syndrome (POS) because of a paradoxical shunt through a patent foramen ovale caused by a large right atrial line-associated thrombus in a male with metastatic oesophageal cancer undergoing chemotherapy. This case is a timely reminder to consider POS amongst differentials for hypoxia as it is often treatable if recognised.

The performance of 11 fingertip pulse oximeters during hypoxemia in healthy human participants with varied, quantified skin pigment.

BACKGROUND: Fingertip pulse oximeters are widely available, inexpensive, and commonly used to make clinical decisions in many settings. Device performance is largely unregulated and poorly characterised, especially in people with dark skin pigmentation. METHODS: Eleven popular fingertip pulse oximeters were evaluated using the US Food and Drug Administration (FDA) Guidance (2013) and International Organization for Standardization Standards (ISO, 2017) in 34 healthy humans with diverse skin pigmentation utilising a controlled desaturation study with arterial oxygen saturation (SaO 2) plateaus between 70% and 100%. Skin pigmentation was assessed subjectively using a perceived Fitzpatrick Scale (pFP) and objectively using the individual typology angle (ITA) via spectrophotometry at nine anatomical sites. FINDINGS: Five of 11 devices had a root mean square error (ARMS) > 3%, falling outside the acceptable FDA performance range. Nine devices demonstrated worse performance in participants in the darkest skin pigmentation category compared with those in the lightest category. A commonly used subjective skin colour scale frequently miscategorised participants as being darkly pigmented when compared to objective quantification of skin pigment by ITA. INTERPRETATION: Fingertip pulse oximeters have variable performance, frequently not meeting regulatory requirements for clinical use, and occasionally contradicting claims made by manufacturers. Most devices showed a trend toward worse performance in participants with darker skin pigment. Regulatory standards do not adequately account for the impact of skin pigmentation on device performance. We recommend that the pFP and other non-standardised subjective skin colour scales should no longer be used for defining diversity of skin pigmentation. Reliable methods for characterising skin pigmentation to improve diversity and equitable performance of pulse oximeters are needed. FUNDING: This study was conducted as part of the Open Oximetry Project funded by the Gordon and Betty Moore Foundation, Patrick J McGovern Foundation, and Robert Wood Johnson Foundation. The UCSF Hypoxia Research Laboratory receives funding from multiple industry sponsors to test the sponsors' devices for the purposes of product development and regulatory performance testing. Data in this paper do not include sponsor's study devices. All data were collected from devices procured by the Hypoxia Research Laboratory for the purposes of independent research. No company provided any direct funding for this study, participated in study design or analysis, or was involved in analysing data or writing the manuscript. None of the authors own stock or equity interests in any pulse oximeter companies. Dr Ellis Monk's time utilised for data analysis, reviewing and editing was funded by grant number: DP2MH132941.

Nocturnal hypoxaemia is common in adults with sickle cell anaemia.

The symptoms and sequelae of sickle cell anaemia (SCA) are caused by the polymerization of deoxygenated sickle haemoglobin, and people with SCA may be uniquely susceptible to adverse outcomes from hypoxia and haemoglobin desaturation. We examined by oximetry adults (aged 18-45 years) with SCA presenting symptoms indicative of polysomnography, at a single institution, irrespective of treatment, for nocturnal hypoxaemia. Clinical labs and blood for in vitro assessments were taken upon enrolment and after 8-12 weeks of oxygen therapy or observation. Of 21 screened participants, nine (43%) had sufficient nocturnal hypoxaemia to warrant oxygen therapy (≥5 min at SpO2 ≤ 88%). Time spent at SpO2 ≤ 88% associated with age (p = 0.0092), annual hospitalizations (p = 0.0018) and anaemia (p = 0.0139), as well as plasma levels of TNFα (p = 0.0019) and IL-4 (p = 0.0147). Longitudinal analysis showed that WBC significantly decreased during the follow-up period in hypoxic individuals but not in non-hypoxic individuals (p = 0.0361 and p = 0.6969 respectively). Plasma levels of CCL2 and IL-1ra tended to increase, while levels of red blood cell reactive oxygen species tended to decrease with oxygen therapy. Overall, nocturnal hypoxaemia was common in this pilot study population and associated with plausible clinical comorbidities; oxygen therapy may decrease inflammation and oxidative damage in hypoxic individuals.

Platypnea-orthodeoxia syndrome (POS) in a patient who had undergone partial liver resection.

A South Asian male in his early 60s presented with acute-onset dyspnoea on postoperative day 4 after undergoing middle hepatic vein sacrificing partial liver resection for epithelioid angiomyolipoma. The patient's SpO2 on presentation was 65% in standing position which improved to 90% in left lateral decubitus. He was suspected of having platypnea-orthodeoxia syndrome (POS) which was confirmed on echocardiogram with microbubble contrast showing a large intracardiac right-to-left shunt. The patient was taken up for transcatheter closure of patent foramen ovale (PFO). A 30 mm Amplatzer PFO Occluder was deployed across the PFO which reduced the intracardiac shunt resulting in an improved arterial saturation as well as immediate relief of patient's symptoms. This case illustrates the importance of suspecting and recognising POS clinically as well as the efficacy of transcatheter closure of PFO in such cases leading to resolution of hypoxaemia in a short span of time.

Recent advances in hypoxia-activated compounds for cancer diagnosis and treatment.

Hypoxia, as a prevalent feature of solid tumors, is correlated with tumorigenesis, proliferation, and invasion, playing an important role in mediating the drug resistance and affecting the cancer treatment outcomes. Due to the distinct oxygen levels between tumor and normal tissues, hypoxia-targeted therapy has attracted significant attention. The hypoxia-activated compounds mainly depend on reducible organic groups including azo, nitro, N-oxides, quinones and azide as well as some redox-active metal complex that are selectively converted into active species by the increased reduction potential under tumor hypoxia. In this review, we briefly summarized our current understanding on hypoxia-activated compounds with a particular highlight on the recently developed prodrugs and fluorescent probes for tumor treatment and diagnosis. We have also discussed the challenges and perspectives of small molecule-based hypoxia-activatable prodrug for future development.

Retrospective analysis of referrals for hypoxic challenge testing in children born preterm.

INTRODUCTION: Children with a history of bronchopulmonary dysplasia (BPD) may be at risk of hypoxaemia at altitude, such as during air travel. We have performed preflight hypoxic challenge testing (HCT) since 2006, incorporating British Thoracic Society (BTS) guidance since 2011, to determine which children may require oxygen during air travel. AIMS: We aimed to compare the outcome of HCTs in children with a history of BPD who met the 2011 BTS criteria and those who did not and, in addition to this, to interrogate the data for factors that may predict the outcome of HCT in this population. METHODS: We performed a retrospective analysis of data from HCTs of children with a history of BPD referred 2006-2020. Cases were excluded if the patient had a respiratory comorbidity, was still on oxygen therapy, if the test was a repeat or if the clinical record was incomplete. Descriptive and univariate analysis of the data was performed, and a binary logistic regression model was fitted. RESULTS: There were 79 HCTs, of which 24/79 (30%) did not meet BTS 2011 guidelines referral criteria. The analysis showed a greater proportion of desaturation in the group that did not meet criteria: 46% vs 27% (no statistical significance). Baseline oxygen saturations were higher in those who did not require oxygen during HCT and this variable was significant when adjusted for confounders. CONCLUSIONS: This study found that the current criteria for referral for preflight testing may incorrectly identify those most at risk and highlights the need for further investigation to ensure those most at risk are being assessed prior to air travel.

Racial and skin color mediated disparities in pulse oximetry in infants and young children.

Race-based and skin pigmentation-related inaccuracies in pulse oximetry have recently been highlighted in several large electronic health record-based retrospective cohort studies across diverse patient populations and healthcare settings. Overestimation of oxygen saturation by pulse oximeters, particularly in hypoxic states, is disparately higher in Black compared to other racial groups. Compared to adult literature, pediatric studies are relatively few and mostly reliant on birth certificates or maternal race-based classification of comparison groups. Neonates, infants, and young children are particularly susceptible to the adverse life-long consequences of hypoxia and hyperoxia. Successful neonatal resuscitation, precise monitoring of preterm and term neonates with predominantly lung pathology, screening for congenital heart defects, and critical decisions on home oxygen, ventilator support and medication therapies, are only a few examples of situations that are highly reliant on the accuracy of pulse oximetry. Undetected hypoxia, especially if systematically different in certain racial groups may delay appropriate therapies and may further perpetuate health care disparities. The role of biological factors that may differ between racial groups, particularly skin pigmentation that may contribute to biased pulse oximeter readings needs further evaluation. Developmental and maturational changes in skin physiology and pigmentation, and its interaction with the operating principles of pulse oximetry need further study. Importantly, clinicians should recognize the limitations of pulse oximetry and use additional objective measures of oxygenation (like co-oximetry measured arterial oxygen saturation) where hypoxia is a concern.

Evaluation of atherosclerosis as a risk factor in COPD patients by measuring the carotid intima-media thickness.

BACKGROUND: This study aimed to evaluate atherosclerosis as comorbidity by measuring the carotid (bulb and common carotid artery) Carotid intima-media thickness in COPD-diagnosed patients and to evaluate the relationship of atherosclerosis with the prevalence of COPD, hypoxemia and hypercapnia. METHODS: This study was conducted out between January 2019-December 2019 consisting of a total of 140 participants (70 COPD-diagnosed patients-70 healthy individuals). The COPD-diagnosed patients have been planned according to the selection and diagnosis criteria as per the GOLD 2019 guide. It is planned to evaluate as per prospective matching case-control study of the carotid thickness, radial gas analysis, spirometric and demographic characteristics of COPD diagnosed patients and healthy individuals. RESULTS: The average Carotid intima-media thickness in COPD patients was 0.8746±0.161 (p<0.05), and the thickness of the carotid bulb was 1.04±0.150 (p<0.05). In the control group, the average CCA intima-media thickness was 0.6650±0.139 (p<0.05), and the thickness of the carotid bulb was 0.8250±0.15(p<0.05) For the carotid thickness that has increased in COPD diagnosed patients a significant relationship is determined between hypoxemia (p<0.05) and hypercapnia(p<0.05). A significant relationship determined between CIMT and severity of COPD (p<0.05) The CIMT was high in COPD patients with hypoxemia and hypercapnia(p<0.05). CONCLUSION: Significant difference was determined between the severity (grades) of COPD (mild, moderate, severe, very severe) in carotid thickness. Also, CIMT was found to be high in patients who is in the early phases of the prevalence of COPD. In COPD-diagnosed patients, it was determined that severity of COPD, hypoxemia, hypercapnia and age were determining factors of atherosclerosis.

A combination of mild-moderate hypoxemia and low compliance is highly prevalent in persistent ARDS: a retrospective study.

BACKGROUND: The Acute Respiratory Distress Syndrome (ARDS) is characterized by lung inflammation and edema, impairing both oxygenation and lung compliance. Recent studies reported a dissociation between oxygenation and compliance (severe hypoxemia with preserved compliance) in early ARDS and COVID-19-related-ARDS (CARDS). During the pandemic, in patients requiring prolonged mechanical ventilation, we observed the opposite combination (mild-moderate hypoxemia but significantly impaired compliance). The purpose of our study was to investigate the prevalence of this combination of mild-moderate hypoxemia and impaired compliance in persistent ARDS and CARDS. METHODS: For this retrospective study, we used individual patient-level data from two independent cohorts of ARDS patients. The ARDSNet cohort included patients from four ARDS Network randomized controlled trials. The CARDS cohort included patients with ARDS due to COVID-19 hospitalized in two intensive care units in Greece. We used a threshold of 150 for PaO2/FiO2 and 30 ml/cmH2O for compliance, estimated the prevalence of each of the four combinations of oxygenation and compliance at baseline, and examined the change in its prevalence from baseline to day 21 in the ARDSNet and CARDS cohorts. RESULTS: The ARDSNet cohort included 2909 patients and the CARDS cohort included 349 patients. The prevalence of the combination of mild-moderate hypoxemia and low compliance increased from baseline to day 21 both in the ARDSNet cohort (from 22.2 to 42.7%) and in the CARDS cohort (from 3.1 to 33.3%). Among surviving patients with low compliance, oxygenation improved over time. The 60-day mortality rate was higher for patients who had mild-moderate hypoxemia and low compliance on day 21 (28% and 56% in ARDSNet and CARDS), compared to those who had mild-moderate hypoxemia and high compliance (20% and 50%, respectively). CONCLUSIONS: Among patients with ARDS who require prolonged controlled mechanical ventilation, regardless of ARDS etiology, a dissociation between oxygenation and compliance characterized by mild-moderate hypoxemia but low compliance becomes increasingly prevalent. The findings of this study highlight the importance of monitoring mechanics in patients with persistent ARDS.

Urinary oxygen tension and its role in predicting acute kidney injury: A narrative review.

Acute kidney injury occurs frequently in the perioperative setting. The renal medulla often endures hypoxia or hypoperfusion and is susceptible to the imbalance between oxygen supply and demand due to the nature of renal blood flow distribution and metabolic rate in the kidney. The current available evidence demonstrated that the urine oxygen pressure is proportional to the variations of renal medullary tissue oxygen pressure. Thus, urine oxygenation can be a candidate for reflecting the change of oxygen in the renal medulla. In this review, we discuss the basic physiology of acute kidney injury, as well as techniques for monitoring urine oxygen tension, confounding factors affecting the reliable measurement of urine oxygen tension, and its clinical use, highlighting its potential role in early detection and prevention of acute kidney injury.

Acute Cardiorespiratory Coupling Impairment in Worsening Sleep Apnea-Related Intermittent Hypoxemia.

OBJECTIVE: Hypoxic load is one of the main characteristics of obstructive sleep apnea (OSA) contributing to sympathetic overdrive and weakened cardiorespiratory coupling (CRC). Whether this association changes with increasing hypoxic load has remained obscure. Therefore, we aimed to study our hypothesis that increasing hypoxic load acutely decreases the CRC. METHODS: We retrospectively analyzed the electrocardiography and nasal pressure signals in 5-min segment pairs (n = 36 926) recorded during clinical polysomnographies of 603 patients with suspected OSA. The segment pairs were pooled into five groups based on the hypoxic load severity described with the the total integrated area under the blood oxygen saturation curve during desaturations. In these severity groups, we determined the frequency-domain heart rate variability (HRV) parameters, the HRV and respiratory high-frequency (HF, 0.15-0.4 Hz) peaks, and the difference between those peaks. We also computed the spectral HF coherence between HRV and respiration in the HF band. RESULTS: The ratio of low-frequency (LF, 0.04-0.15 Hz) to HF power increased from 1.047 to 1.805 (p < 0.001); the difference between the HRV and respiratory HF peaks increased from 0.001 Hz to 0.039 Hz (p < 0.001); and the spectral coherence between HRV and respiration in the HF band decreased from 0.813 to 0.689 (p < 0.001) as the hypoxic load increased. CONCLUSION AND SIGNIFICANCE: The vagal modulation decreases and CRC weakens significantly with increasing hypoxic load. Thus, the hypoxic load could be utilized more thoroughly in contemporary OSA diagnostics to better assess the severity of OSA-related cardiac stress.

Apnea-hypopnea index and the polysomnographic risk factors for predicting 5- to 8-year mortality in patients with OSA.

BACKGROUND: The purpose of this study was to investigate the long-term mortality rates of patients with obstructive sleep apnea (OSA) who received an overnight polysomnogram (PSG) for obtaining the diagnosis and to determine the relationship between PSG parameters and overall mortality. METHODS: Between 2007 and 2013, patients who had overnight PSG and were diagnosed with OSA were included in the study. Factors which are thought to influence mortality were assessed for 5-year and overall survival using the log rank test and Kaplan-Meier survival curves. Using multivariable Cox regression analysis, a model was constructed for factors influencing 5-year and overall survival. RESULTS: A total of 762 patients with a mean age of 52.7 (±10.8) and a dominance of men (74.7%) were studied. Gender, OSA severity subgroups, and apnea hypopnea index (AHI) were not statistically significantly associated with either 5-year or overall mortality (p<0.05 for both). Age, having a cardiovascular comorbidity, proportion of rapid eye movement (%REM), and total sleep time with an oxyhemoglobin saturation of less than 90% (T90) all showed a significant correlation with overall all-cause mortality in the model. For 5-year mortality and overall mortality, the hazard ration (HR) for T90 was 3.6 (95% CI (1.6-8.0) p=0.001) and 3 (95% CI (1.6-5.7) p=0.001), respectively. CONCLUSION: The study findings suggest that not AHI but PSG parameters of hypoxia, mainly T90, having cardiovascular comorbidity, and %REM sleep were significant risk factors for all-cause mortality in patients with OSA. The association of OSA, hypoxia, and mortality is an area that deserves further study.