The relationship between intermittent hypoxemia events and neural outcomes in neonates.

This brief review examines 1) patterns of intermittent hypoxemia in extremely preterm infants during early postnatal life, 2) the relationship between neonatal intermittent hypoxemia exposure and outcomes in both human and animal models, 3) potential mechanistic pathways, and 4) future alterations in clinical care that may reduce morbidity. Intermittent hypoxemia events are pervasive in extremely preterm infants (<28 weeks gestation at birth) during early postnatal life. An increased frequency of intermittent hypoxemia events has been associated with a range of poor neural outcomes including language and cognitive delays, motor impairment, retinopathy of prematurity, impaired control of breathing, and intraventricular hemorrhage. Neonatal rodent models have shown that exposure to short repetitive cycles of hypoxia induce a pathophysiological cascade. However, not all patterns of intermittent hypoxia are deleterious and some may even improve neurodevelopmental outcomes. Therapeutic interventions include supplemental oxygen, pressure support and pharmacologic drugs but prolonged hyperoxia and pressure exposure have been associated with cardiopulmonary morbidity. Therefore, it becomes imperative to distinguish high risk from neutral and/or even beneficial patterns of intermittent hypoxemia during early postnatal life. Identification of such patterns could improve clinical care with targeted interventions for high-risk patterns and minimal or no exposure to treatment modalities for low-risk patterns.

Cluster headache pathophysiology - insights from current and emerging treatments.

Cluster headache is a debilitating primary headache disorder that affects approximately 0.1% of the population worldwide. Cluster headache attacks involve severe unilateral pain in the trigeminal distribution together with ipsilateral cranial autonomic features and a sense of agitation. Acute treatments are available and are effective in just over half of the patients. Until recently, preventive medications were borrowed from non-headache indications, so management of cluster headache is challenging. However, as our understanding of cluster headache pathophysiology has evolved on the basis of key bench and neuroimaging studies, crucial neuropeptides and brain structures have been identified as emerging treatment targets. In this Review, we provide an overview of what is known about the pathophysiology of cluster headache and discuss the existing treatment options and their mechanisms of action. Existing acute treatments include triptans and high-flow oxygen, interim treatment options include corticosteroids in oral form or for greater occipital nerve block, and preventive treatments include verapamil, lithium, melatonin and topiramate. We also consider emerging treatment options, including calcitonin gene-related peptide antibodies, non-invasive vagus nerve stimulation, sphenopalatine ganglion stimulation and somatostatin receptor agonists, discuss how evidence from trials of these emerging treatments provides insights into the pathophysiology of cluster headache and highlight areas for future research.

Adjuvant High-Flow Normobaric Oxygen After Mechanical Thrombectomy for Anterior Circulation Stroke: a Randomized Clinical Trial.

Adjuvant neuroprotective therapies for acute ischemic stroke (AIS) have demonstrated benefit in animal studies, albeit without human translation. We investigated the safety and efficacy of high-flow normobaric oxygen (NBO) after endovascular recanalization in anterior circulation stroke. This is a prospective randomized controlled study. Eligible patients were randomized to receive high-flow NBO by a Venturi mask (FiO2 50%, flow 15 L/min) or routine low-flow oxygen supplementation by nasal cannula (flow 3 L/min) after vessel recanalization for 6 h. Patient demographics, procedural metrics, complications, functional outcomes, symptomatic intracranial hemorrhage (sICH), and infarct volume were assessed. A total of 91 patients were treated with high-flow NBO. NBO treatment revealed a common odds ratio of 2.2 (95% CI, 1.26 to 3.87) favoring the distribution of global disability scores on the mRS at 90 days. The mortality at 90 days was significantly lower in the NBO group than in the control group, with an absolute difference of 13.86% (rate ratio, 0.35; 95% CI, 0.13-0.93). A significant reduction of infarct volume as determined by MRI was noted in the NBO group. The median infarct volume was 9.4 ml versus 20.5 ml in the control group (beta coefficient, - 20.24; 95% CI, - 35.93 to - 4.55). No significant differences were seen in the rate of sICH, pneumonia, urinary infection, and seizures between the 2 groups. This study suggests that high-flow NBO therapy after endovascular recanalization is safe and effective in improving functional outcomes, decreasing mortality, and reducing infarct volumes in anterior circulation stroke patients within 6 h from stroke onset.

Has the introduction of high-flow nasal cannula modified the clinical characteristics and outcomes of infants with bronchiolitis admitted to pediatric intensive care units? A retrospective study.

BACKGROUND: This study aimed to assess how the emergence of high-flow nasal cannula (HFNC) has modified the demographic and clinical characteristics as well as outcomes of infants with bronchiolitis admitted to a pediatric intensive care unit (PICU). METHODS: This was a single-center retrospective study including infants aged 1 day to 6 months with bronchiolitis requiring HFNC, noninvasive ventilation (NIV), or invasive ventilation on admission. RESULTS: A total of 252 infants (mean age 53±36 days) were included in the study. The use of HFNC increased from 18 (21.4%) during 2013-2014 to 53 infants (55.2%) during 2015-2016. The length of stay in the PICU decreased over time from 4.7±2.9 to 3.5±2.7 days (P<0.01) but the hospital length of stay remained similar (P=0.17). On admission, patients supported by HFNC as the first-line therapy were older. The PICU length of stay was similar according to the type of respiratory support (P=0.16), but the hospital length of stay was longer for patients supported by HFNC (P=0.01). CONCLUSION: The distribution of respiratory support has significantly changed over time for patients with bronchiolitis and HFNC is increasingly used. The demographic and clinical characteristics of the have not changed over time. However, the PICU length of stay decreased significantly.

Use of Noninvasive Ventilation and High-Flow Nasal Cannulae Therapy for Infants and Children with Acute Respiratory Distress Outside of Paediatric Intensive Care: A review article.

Noninvasive ventilation (NIV) and high-flow nasal cannulae therapy (HFNCT) are first-line methods of treatment for children presenting with acute respiratory distress, with paediatric intensive care units (PICUs) providing an ideal environment for subsequent treatment monitoring. However, the availability of step-down units, where NIV and HFNCT can be safely utilised, has reduced the need for such patients to be admitted to PICUs, thereby leading to the better overall utilisation of critical care resources. In addition, NIV and HFNCT can also be used during transport instead of invasive ventilation, thus avoiding the complications associated with the latter approach. This review article examines the safety and applicability of these respiratory support approaches outside of paediatric intensive care as well as various factors associated with treatment success or failure.

2018 Year in Review: Noninvasive Respiratory Support.

Noninvasive respiratory support refers to strategies aimed at providing oxygenation and/or ventilation without the use of an artificial airway. These strategies include the use of standard oxygen delivery devices (face masks, low-flow nasal cannulas), noninvasive ventilation, and high-flow nasal cannula. Considerable interest has been generated recently as to which therapy provides the optimum noninvasive support. This review examined the important literature related to noninvasive respiratory support published in 2018.

Home Oxygen and 2-Year Outcomes of Preterm Infants With Bronchopulmonary Dysplasia.

OBJECTIVES: To compare medical and developmental outcomes over the first 2 years of life in extremely preterm infants with bronchopulmonary dysplasia (BPD) who were discharged on supplemental oxygen via nasal cannula with outcomes of infants with a similar severity of respiratory illness who were discharged breathing in room air. METHODS: We performed a propensity score-matched cohort study. Eligible infants were born at <27 weeks' gestation, were receiving supplemental oxygen or respiratory support at 36 weeks' postmenstrual age, and were assessed at 18 to 26 months' corrected age. Study outcomes included growth, resource use, and neurodevelopment between discharge and follow-up. Outcomes were compared by using multivariable models adjusted for center and age at follow-up. RESULTS: A total of 1039 infants discharged on supplemental oxygen were propensity score matched 1:1 to infants discharged breathing in room air. Infants on oxygen had a marginal improvement in weight z score (adjusted mean difference 0.11; 95% confidence interval [CI] 0.00 to 0.22), with a significantly improved weight-for-length z score (adjusted mean difference 0.13; 95% CI 0.06 to 0.20) at 22 to 26 months' corrected age. Infants on oxygen were more likely to be rehospitalized for respiratory illness (adjusted relative risk 1.33; 95% CI 1.16 to 1.53) and more likely to use respiratory medications and equipment. Rates of neurodevelopmental impairment were similar between the groups. CONCLUSIONS: In this matched cohort of infants with BPD, postdischarge oxygen was associated with marginally improved growth and increased resource use but no difference in neurodevelopmental outcomes. Ongoing and future trials are critical to assess the efficacy and safety of postdischarge supplemental oxygen for infants with BPD.

Characteristics at the time of oxygen initiation associated with its adherence: Findings from the COPD Long-term Oxygen Treatment Trial.

RATIONALE: Characteristics associated with adherence to long-term oxygen therapy (LTOT) in COPD remain unclear. OBJECTIVES: To identify patient characteristics at the time of oxygen initiation associated with its adherence. METHODS: We conducted a secondary analysis of data from 359 COPD participants assigned to oxygen in the Long-term Oxygen Treatment Trial. Participants were prescribed continuous (n = 214) or intermittent (n = 145) oxygen based on desaturation patterns at study entry. At the time of initial prescription, participants rated their perceived readiness, confidence, and importance to use oxygen on a 0-10 scale (0 = not at all, 10 = very much). During follow-up, they self-reported average hours per day of use (adherence). Adherence was averaged over short-term (0-30 days), medium-term (months 9-12), and long-term (month 13 to last follow-up) intervals. Multivariable logistic regression models explored characteristics associated with high adherence (≥16 h/day [continuous] or ≥8 h/day [intermittent]) during each time interval. RESULTS: Participant readiness, confidence, and importance at the time of oxygen initiation were associated with high short- and medium-term adherence. For each unit increase in baseline readiness, the odds of high short-term adherence increased by 21% (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.05-1.40) and 94% (OR 1.94, 95% CI 1.45-2.59) in the continuous and intermittent groups, respectively. In both groups, high adherence in the medium-term was associated with high adherence in the long-term (continuous, OR 12.49, 95% CI 4.90-31.79; intermittent, OR 38.08, 95% CI 6.96-208.20). CONCLUSIONS: Readiness, confidence, and importance to use LTOT at initiation, and early high adherence, are significantly associated with long-term oxygen adherence.

New Perspectives in Oxygen Therapy Titration: Is Automatic Titration the Future? / Nuevas perspectivas en la titulación de la oxigenoterapia: ¿es la titulación automática el futuro?

Oxygen therapy, like all technology-based treatments, is continuously evolving. There are no doubts as to its effectiveness in the treatment of acute and respiratory failure in different clinical scenarios. However, the dosing guidelines for oxygen therapy are not as strict as for other treatments. The use of higher than necessary flows over excessively long periods, derived from the clinician's perception of it as a 'life-saving treatment with few side effects', has led to a rather liberal use of this intervention, despite evidence that overuse and suboptimal adjustment can be harmful. The titration of oxygen therapy, which is traditionally performed manually, has been shown to be beneficial. Recently, new devices have been developed that automatically adjust oxygen flow rates to the needs of each patient, in order to maintain stable oxygen saturation levels. These closed-loop oxygen supply systems can potentially reduce medical error, improve morbidity and mortality, and reduce care costs. Familiarizing the medical community with these technological advances will improve awareness of the risks of the inappropriate use of oxygen therapy. The aim of this paper is to provide an update of recent developments in oxygen therapy titration.

Risk prediction tool for use and predictors of duration of postoperative oxygen therapy in children undergoing non-cardiac surgery: a case-control study.

BACKGROUND: We aimed to construct a prediction tool for postoperative oxygen therapy and determine predictors of duration of use among children undergoing non-cardiac surgery. METHODS: Data from this case-control study was obtained from a database of 9820 children aged < 15 years who underwent general anesthesia between January 2010 and December 2013 at a tertiary care hospital in southern Thailand. The primary outcomes were the use and duration (hours) of postoperative oxygen therapy (cases). Cases were matched with controls on age group and year of surgery in a ratio of 1:4. A negative binomial hurdle model was used to obtain significant predictors of any use and number of hours of oxygen therapy. A risk score was derived from the coefficients of the significant predictors. The risk score, adjusted odds ratio (OR) for any use and count ratio (CR) for duration of postoperative oxygen therapy and 95% confidence interval (CI) were determined. RESULTS: A total of 288 cases and 1152 controls were included. The median (inter-quartile range) duration of oxygen therapy delivered was 17 (9-22) hours. An optimal risk score for predictors of oxygen use was 12 (0-32) giving an area under the receiver operating characteristic curve of 0.93. Predictors of high risk need for oxygen therapy (score ≥ 12) were thoracic surgery (OR = 278, 95% CI = 44.6-1733) and having desaturation perioperatively (OR = 459.8, 95% CI = 169.7-1246). Intermediate risk factors (score 8-11) were having bronchospasm (OR = 92.4, 95% CI = 29.7-287.5) and upper airway obstruction/laryngospasm (OR = 61.5, 95% CI = 14.4-262.4) perioperatively. Significant predictors of duration of oxygen therapy were probably difficult airway (CR = 2.2, 95% CI = 1.4-3.5), history of delayed development (CR = 2.3, 95% CI = 1.5-3.6), airway (CR = 3.0, 95% CI = 1.6-5.8), orthopedic (CR = 2.1, 95% CI = 1.1-4.3), thoracic (CR = 4.9, 95% CI = 2.3-10.1) and abdominal surgery (CR = 4.2, 95% CI = 2.1-8.1), compared to eye surgery. CONCLUSIONS: Our risk prediction tool for the use of postoperative oxygen therapy provided a high predictive ability. Children who have thoracic surgery, desaturation, bronchospasm, upper airway obstruction or laryngospasm will most likely need postoperative oxygen therapy, regardless of other factors, while those with a probably difficult airway, history of delayed development, or thoracic/abdominal surgery will most likely need longer duration of oxygen therapy.

High flow nasal therapy in perioperative medicine: from operating room to general ward.

BACKGROUND: High flow nasal therapy (HFNT) is a technique in which humidified and heated gas is delivered to the airways through the nose via small nasal prongs at flows that are higher than the rates generally applied during conventional oxygen therapy. The delivered high flow rates combine mixtures of air and oxygen and enable different inspired oxygen fractions ranging from 0.21 to 1. HFNT is increasingly used in critically ill adult patients, especially hypoxemic patients in different clinical settings. MAIN BODY: Noninvasive ventilation delivers positive pressure (end-expiratory and inspiratory pressures or continuous positive airway pressure) via different external interfaces. In contrast, HFNT produces different physiological effects that are only partially linked to the generation of expiratory positive airway pressure. HFNT and noninvasive ventilation (NIV) are interesting non-invasive supports in perioperative medicine. HFNT exhibits some advantages compared to NIV because HFNT is easier to apply and requires a lower nursing workload. Tolerance of HFNT remains a matter of intense debate, and it may be related to selected parameters. Patients receiving HFNT and their respiratory patterns should be closely monitored to avoid delays in intubation despite correct oxygenation parameters. CONCLUSION: HFNT seems to be an interesting noninvasive support in perioperative medicine. The present review provides anesthesiologists with an overview of current evidence and practical advice on the application of HFNT in perioperative medicine in adult patients.

High-flow nasal cannula in adults with acute respiratory failure and after extubation: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal cannula (HFNC) can be used as an initial support strategy for patients with acute respiratory failure (ARF) and after extubation. However, no clear evidence exists to support or oppose HFNC use in clinical practice. We summarized the effects of HFNC, compared to conventional oxygen therapy (COT) and noninvasive ventilation (NIV), on important outcomes including treatment failure and intubation/reintubation rates in adult patients with ARF and after extubation. METHODS: We searched 4 electronic databases (Pubmed, EMBASE, Scopus, and Web of Science) to identify randomized controlled trials (RCTs) comparing the effects of HFNC with either COT or NIV on rates of 1) treatment failure and 2) intubation/reintubation in adult critically ill patients. RESULTS: We identified 18 RCTs (n = 4251 patients) in pooled analyses. As a primary mode of support, HFNC treatment reduced the risk of treatment failure [Odds Ratio (OR) 0.65; 95% confidence interval (CI) 0.43-0.98; p = 0.04; I2 = 32%] but had no effect on preventing intubation (OR, 0.74; 95%CI 0.45-1.21; p = 0.23; I2 = 0%) compared to COT. When used after extubation, HFNC (vs. COT) treatment significantly decreased reintubation rate (OR 0.46; 95%CI 0.33-0.63; p < 0.00001; I2 = 30%) and extubation failure (OR 0.43; 95%CI 0.25-0.73; p = 0.002; I2 = 66%). Compared to NIV, HFNC significantly reduced intubation rate (OR 0.57; 95%CI 0.36-0.92; p = 0.02; I2 = 0%) when used as initial support, but did no favorably impact clinical outcomes post extubation in few trials. CONCLUSIONS: HFNC was superior to COT in reducing treatment failure when used as a primary support strategy and in reducing rates of extubation failure and reintubation when used after extubation. In few trials, HFNC reduced intubation rate compared to NIV when used as initial support but demonstrated no beneficial effects after extubation.

A wolf in sheep's clothing? Patients' and healthcare professionals' perceptions of oxygen therapy: An interpretative phenomenological analysis.

BACKGROUND: Despite emerging evidence and guidelines, poor prescribing and administration of oxygen therapy persists. This study aimed to explore healthcare professionals' (HCPs) and patients' perceptions of oxygen. DESIGN: Semi-structured interviews with 28 patients and 34 HCPs. FINDINGS: Three master themes uncovered: oxygen as a panacea, the burden of oxygen and antecedents to beliefs. Patients used oxygen for breathlessness and as an enabler; they were grateful to oxygen and accepted it as part of the disease. HCPs used oxygen because it helps patients; it works; and it makes HCPs feel better. But oxygen is not benign and a burden is evident with potential antecedents to beliefs revealed. SUMMARY: The findings suggest that a set of fixed beliefs regarding oxygen exist, influenced by several impacting factors. The perception that oxygen is a universal remedy presides, but is, at times, contradictory. These findings will raise awareness of entrenched cultures, influence future educational and research strategies, and inform policy.

Prescribing Oxygen for Cluster Headache: A Guide for the Provider.

BACKGROUND: Oxygen is the standard of care for acute treatment of cluster headache. CMS, the US Centers for Medicaid and Medicare Services, has made the indefensible decision to not cover oxygen for cluster headache for patients with Medicaid and Medicare insurance, despite the evidence and professional guidelines. Commercial insurance generally covers oxygen for cluster headache. OBJECTIVE: This is a "how-to" guide for successfully prescribing oxygen in the US. SUMMARY: Prescription information is provided that can be incorporated as dot phrases, smart sets, or other standard templates for prescribing oxygen for cluster patients. In many states, oxygen is affordable and can be prescribed for Medicaid and Medicare patients who wish to pay cash. Welding or nonmedical grade industrial oxygen is almost the same cost as medical oxygen. However, it is less pure, lacks the same inspection of tanks, and is delivered without regulators to provide appropriate flow rates. Patients who pay cash should be strongly encouraged to buy medical oxygen.

Economics of Inhaled Oxygen Use as an Acute Therapy for Cluster Headache in the United States of America.

BACKGROUND: Cluster headache (CH) is a primary headache disorder associated with low levels of diagnosis and high unmet medical need. The pain attacks, associated anxiety, and fear in anticipation of the attacks are extremely debilitating to a patient with CH. For acute therapy, treatment guidelines recommend inhalation of high flow oxygen during the period of an attack. However, the use of oxygen for treatment of CH remains largely underutilized. OBJECTIVES: The objectives of the study, which covered each of the US states, were to map the current market landscape of medical grade oxygen for use in CH and to develop a cost simulator based on a patient's needs and geography. METHODS: Desk research was undertaken to obtain price lists and product catalogs from wholesale and retail suppliers of medical grade oxygen across all US states. Base case scenarios for chronic and episodic forms of CH were assumed. A cost simulator was used to calculate the cost of oxygen use using inputs including the state in USA, tank size and price, exacerbations per year, duration of exacerbation, attacks per day, flow rate and duration of flow. Information was also collected to determine if healthcare insurers covered the costs of home oxygen use for CH. RESULTS: Out of the 42 US states where pricing information of medical grade oxygen was available from suppliers, in 38 states the annual cost of high-flow oxygen for a patient with episodic CH was estimated to be <$1000. In 39 states, the annual cost of high-flow oxygen for a patient with chronic CH was estimated to be <$5000. Most of the home oxygen suppliers were familiar with CH and stocked the special non-rebreather masks and regulators necessary for this condition. It was found that many of the private commercial healthcare insurance providers reimbursed the cost of oxygen use for CH. However, the US Centers for Medicare and Medicaid Services (CMS) maintains there is insufficient evidence for coverage and continues to deny coverage for US Medicare and Medicaid patients. CONCLUSIONS: Results from our study showed that the current costs for oxygen use as an acute therapy in CH are not prohibitively expensive for patients and healthcare insurance providers. Apart from CMS, many insurers do reimburse the cost of oxygen use for CH. Our study suggests that further research is needed to determine if a lack of physician awareness about treatments and ways to prescribe are barriers for patients to access the high-flow oxygen treatment.

Pediatric Oxygen Therapy: A Review and Update.

Oxygen is a colorless, odorless, tasteless gas that is utilized by the body for respiration. Oxygen has played a major role in respiratory care. Oxygen therapy is useful in treating hypoxemia but is often thought of as a benign therapy. After many years of study, we have learned a great deal of the benefits and potential risk of this powerful drug. Today oxygen gas is cheap, widely available, and easy to administer. Oxygen delivery devices vary in cost from a few cents for a simple nasal cannula to $25-$50 for some humidified systems. Undoubtedly, oxygen therapy is an important tool and has saved many lives and improved others. However, oxygen therapy risk, cost, and benefits should be considered in the same way as other drugs and titrated to a measured end point to avoid excessive or inadequate dosing. Withholding oxygen can have a detrimental effect, yet continuing to provide oxygen therapy when it is no longer indicated can prolong hospitalization and increase the cost of care. This comprehensive review begins with an assessment of need and a review of physiologic effects, potential toxicities, and common delivery devices, and it ends with advances in oxygen therapy with a focus on the pediatric patient.