Oxygen
Number: 0002
Table Of Contents
PolicyApplicable CPT / HCPCS / ICD-10 Codes
Background
References
Policy
Scope of Policy
This Clinical Policy Bulletin addresses home oxygen therapy.
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Medical Necessity
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Home oxygen therapy is only considered medically necessary if all of the following conditions are met:
- The treating physician has determined that the member has a severe lung disease or hypoxia-related symptoms that might be expected to improve with oxygen therapy, and
- The member's blood gas study meets the criteria stated below, and
- The qualifying blood gas study was performed by a physician or by a qualified provider or supplier of laboratory services, and
- The qualifying blood gas study was obtained under the following conditions:
- If the qualifying blood gas study is performed during an inpatient hospital stay, the reported test must be the one obtained closest to, but no earlier than 2 days prior to the hospital discharge date, or
- If the qualifying blood gas study is not performed during an inpatient hospital stay and the oxygen is being prescribed for chronic conditions, the reported test must be performed while the member is in a chronic stable state – i.e., not during a period of acute illness or an exacerbation of their underlying disease, and
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Alternative treatment measures have been tried or considered and deemed clinically ineffective.
In this policy, the term blood gas study refers to either an oximetry test or an arterial blood gas test.
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Where the above-listed criteria are met, Aetna considers oxygen for home use medically necessary durable medical equipment (DME) in the following circumstances:
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Diagnosis of severe lung disease and qualifying lab values (see Appendix):
- Bronchiectasis
- Chronic obstructive pulmonary disease (COPD) with severe hypoxemia
- Cystic fibrosis
- Diffuse interstitial lung disease
- Pediatric bronchopulmonary dysplasia (BPD)
- Widespread pulmonary neoplasm;
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Diagnosis of other hypoxia-related symptoms or findings with qualifying lab values (see Appendix):
- Erythrocytosis (hematocrit greater than 55 %)
- Pulmonary hypertension
- Recurring congestive heart failure due to chronic cor-pulmonale;
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Other diagnoses of hypoxia-related symptoms or findings with qualifying lab values (see Appendix) that usually resolve with limited or short-term oxygen therapy:
- Asthma
- Bronchitis
- Croup
- Pneumonia.
Although treatment of these diagnoses (pneumonia, asthma, croup, bronchitis) may be considered medically necessary for short-term therapy (generally less than 1 month duration), it is not considered medically necessary on an ongoing basis absent special circumstances. Requests for more than episodic oxygen for these diagnoses are subject to medical review. For ongoing oxygen treatment, repeat qualifying lab values are reviewed on a monthly basis.
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Other diagnoses for which short-term use of oxygen has been shown to be beneficial (unrelated to hypoxia), e.g., cluster headaches may be certified as medically necessary on an individual case basis upon medical review:
- Cluster headaches that meet the diagnostic criteria used by the International Headache Society to form a definitive diagnosis of CH (see Appendix), where the headaches are refractory to prescription medications;
- Hemoglobinopathies - self-administration of adjunctive short-term oxygen therapy in the outpatient setting has been shown to be beneficial and reduce hospitalizations in individuals with hemoglobinopathies, such as hemoglobin sickle cell disease, during vaso-occlusive crisis exacerbated by hypoxia;
- Infants with BPD may have variable oxygen needs, thus, consideration on a case-by-case basis may be required in the absence of documentation of otherwise qualifying oxygen saturation values.
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Oxygen therapy is considered not medically necessary for all other indications, including the following:
- Angina pectoris in the absence of hypoxemia - this condition is generally not the result of a low oxygen level in the blood and there are other preferred treatments;
- Dyspnea without cor pulmonale or evidence of hypoxemia;
- Severe peripheral vascular disease resulting in clinically evident desaturation in one or more extremities but in the absence of systemic hypoxemia; There is no evidence that increased PO2 will improve the oxygenation of tissues with impaired circulation;
- Terminal illnesses that do not affect the respiratory system.
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Oxygen Delivery Systems
The following delivery systems may be considered medically necessary:
Stationary:
Oxygen concentrators, liquid reservoirs, or large cylinders (usually K or H size) that are designed for stationary use:
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Considered medically necessary for members who do not regularly go beyond the limits of a stationary oxygen delivery system with a 50-ft tubing or those who use oxygen only during sleep;
Portable:
Systems that weigh 10 lbs or more and are designed to be transported but not easily carried by the member, e.g., a steel cylinder attached to wheels (“stroller”):
- Considered medically necessary for members who occasionally go beyond the limits of a stationary oxygen delivery system with 50-ft tubing for less than 2 hours per day for most days of the week (minimum 2 hours/week)
- Preset portable oxygen units are considered not medically necessary;
Ambulatory:
Systems that weigh less than 10 lbs when filled with oxygen, are designed to be carried by the member, and will last for 4 hours at a flow equivalent to 2 L/min continuous flow; e.g., liquid refillable units and aluminum or fiber wrapped light-weight cylinders, with or without oxygen conserving devices:
- Considered medically necessary for members who regularly go beyond the limits of a stationary oxygen delivery system with a 50-ft tubing for 2 hours or more per day and for most days of the week (minimum 6 hours/week)
- Prescription based on the activity status of the member, the appropriate oxygen delivery system will be delivered;
Portable Oxygen Concentrators:
Portable oxygen concentrators and combination stationary/portable oxygen systems are considered medically necessary as an alternative to ambulatory oxygen systems for members who meet both of the following criteria:
- Member meets criteria for ambulatory oxygen systems (see above); and
- Member is regularly (at least monthly) away from home for durations that exceed the capacity of ambulatory oxygen systems.
A second oxygen tank (spare tank) is considered not medically necessary, except in instances where the member is dependent on continuous oxygen. A single oxygen tank may be considered medically necessary for a person who is dependent on an oxygen concentrator.
Emergency or standby oxygen systems are considered not medically necessary.Duplicate oxygen systems are considered convenience items and not medically necessary, including but not limited to: provision of both a stationary and portable oxygen concentrator; or provision of both an oxygen transfilling systems and a portable oxygen system.
Notes: Electrical generators do not meet Aetna's definition of DME because they are not primarily medical in nature.
Humidifiers (e.g., Vapotherm) for oxygen nasal cannula are not separately reimbursable.
Rental versus purchase: Aetna considers the rental or, if less costly, purchase of oxygen equipment medically necessary when selection criteria are met.
The reasonable useful lifetime for oxygen equipment is 5 years. The RUL is not based on the chronological age of the equipment. It starts on the initial date of service and runs for 5 years from that date.
Ambulatory oxygen systems and portable oxygen concentrators are considered not medically necessary for members who qualify for oxygen solely based on blood gas studies obtained during sleep.
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Reassessment
Except as noted in short-term indications, reassessment of oxygen needs through pulse oximetry or arterial blood gas is required and must be performed by an independent respiratory provider at 12 months after the initiation of therapy for persons who qualify for oxygen based upon an arterial PO2 at or below 55 mm Hg or an arterial oxygen saturation at or below 88 %, or at 3 months after initiation for persons who qualify for oxygen based upon an arterial PO2 between 56 to 59 mm Hg or an arterial oxygen saturation of 89 % with dependent edema, P pulmonale, or erythrocythemia. Additional reassessments may be requested at any time at the discretion of Aetna. Reassessments must be done by an Aetna participating oxygen-qualifying company that is in no way connected to the company supplying the oxygen therapy (as per Medicare guidelines). The member's primary care and/or treating doctor must be notified for authorization of all testing and treatment changes, including the discontinuation of coverage for oxygen therapy.
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Aetna considers rental of airline oxygen tank medically necessary when members meet the criteria for oxygen for home use listed above and they are not allowed to use their own portable oxygen tank on the plane.
Note: This policy applies to all products with coverage for DME. Under plans that do not cover DME, domiciliary oxygen may be covered on a case-by-case basis subject to medical review to avert hospital confinement.
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Experimental, Investigational, or Unproven
Oxygen for home use are considered experimental, investigational, or unproven for the following because its effectiveness for these indications has not been established:
- Treatment of migraine headaches
- Treatment of obstructive sleep apnea
- Treatment of pediatric seizures
- Prophylactic home oxygen to reduce transfusion-related adverse events in pregnant women with sickle cell disease).
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Related Policies
- CPB 0339 - Pulse Oximetry and Capnography for Home Use - for the use of pulse oximetry in periodically re-assessing the need for long-term oxygen in the home)
Background
This policy is supported by criteria from the Centers for Medicare & Medicaid Services (CMS).
In a Cochrane review, Bennett et al (2008) evaluated the safety and effectiveness of hyperbaric oxygen therapy (HBOT) and normo-baric oxygen therapy (NBOT) for treating and preventing migraine and cluster headaches. These investigators searched the following in May 2008: CENTRAL, MEDLINE, EMBASE, CINAHL, DORCTIHM and reference lists from relevant articles. Relevant journals were hand-searched and researchers contacted. Randomized trials comparing HBOT or NBOT with one another, other active therapies, placebo (sham) interventions or no treatment in patients with migraine or cluster headache were selected for analysis. Three reviewers independently evaluated study quality and extracted data. A total of 9 small trials involving 201 participants were included; 5 trials compared HBOT versus sham therapy for acute migraine, 2 compared HBOT to sham therapy for cluster headache and 2 evaluated NBOT for cluster headache. Pooling of data from 3 trials suggested that HBOT was effective in relieving migraine headaches compared to sham therapy (relative risk (RR) 5.97, 95 % confidence interval (CI): 1.46 to 24.38, p = 0.01). There was no evidence that HBOT could prevent migraine episodes, reduce the incidence of nausea and vomiting or reduce the requirement for rescue medication. There was a trend to better outcome in a single trial evaluating HBOT for the termination of cluster headache (RR 11.38, 95 % CI: 0.77 to 167.85, p = 0.08), but this trial had low power. NBOT was effective in terminating cluster headache compared to sham in a single small study (RR 7.88, 95 % CI: 1.13 to 54.66, p = 0.04), but not superior to ergotamine administration in another small trial (RR 1.17, 95 % CI: 0.94 to 1.46, p = 0.16). Seventy-six per cent of patients responded to NBOT in these 2 trials. No serious adverse effects of HBOT or NBOT were reported. The authors concluded that there was some evidence that HBOT was effective for the termination of acute migraine in an unselected population, and weak evidence that NBOT was similarly effective in cluster headache. Given the cost and poor availability of HBOT, more research should be done on patients unresponsive to standard therapy. NBOT is cheap, safe and easy to apply, so will probably continue to be used despite the limited evidence in this review.
The National Institute for Health and Clinical Excellence (NICE)’s guideline on "Diagnosis and management of headaches in young people and adults" (2012) recommended oxygen therapy for cluster headaches; but did not mention its use for migraines.
Jurgens et al (2013) noted that while inhalation of high-flow 100 % oxygen is highly effective in cluster headache, studies on its efficacy in migraine are sparse and controversial. These researchers reported the case of a 22-year old patient with an 8-year history of strictly unilateral migraine without aura but cranial autonomic symptoms. She repeatedly responded completely to inhalation of high-flow pure oxygen within 15 mins but suffered from recurrence of attacks within 30 mins after discontinuation. The authors concluded that in line with experimental animal studies, this case suggested a clinically relevant efficacy of inhaled oxygen in patients with migraine with accompanying cranial autonomic symptoms.
Furthermore, UpToDate reviews on "Acute treatment of migraine in adults" (Bajwa and Sabahat, 2013a) and "Preventive treatment of migraine in adults" (Bajwa and Sabahat, 2013b) do not mention the use of oxygen as a management tool.
Mehta et al (2013) stated that hypoxemia is an immediate consequence of obstructive sleep apnea (OSA). Oxygen (O2) administration has been used as an alternative treatment in patients with OSA who do not adhere to continuous positive airway pressure (CPAP) in order to reduce the deleterious effects of intermittent hypoxemia during sleep. These researchers investigated the effects of O2 therapy on patients with OSA. They conducted a systematic search of the databases Medline, Embase, Cochrane Central Register of Controlled Trials (first Quarter 2011), Cochrane Database of Systematic Reviews (from 1950 to February 2011). The search strategy yielded 4,793 citations. Irrelevant papers were excluded by title and abstract review, leaving 105 manuscripts. These investigators reviewed all prospective studies that included:
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a target population with OSA,
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O2 therapy and/or CPAP as a study intervention,
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the effects of O2 on the apnea-hypopnea index (AHI), nocturnal hypoxemia, or apnea duration.
These researchers identified 14 studies including a total of 359 patients; 9 studies were of single cohort design, while 5 studies were randomized control trials (RCTs) with 3 groups (CPAP, O2, and placebo/sham CPAP). When CPAP was compared to O2 therapy, all but 1 showed a significant improvement in AHI. Ten studies demonstrated that O2 therapy improved oxygen saturation versus placebo. However, the average duration of apnea and hypopnea episodes were longer in patients receiving O2 therapy than those receiving placebo. The authors concluded that the findings of this review showed that O2 therapy significantly improves oxygen saturation in patients with OSA. However, it may also increase the duration of apnea-hypopnea events.
Gottlieb and colleagues (2014) stated that OSA is associated with hypertension, inflammation, and increased cardiovascular risk. Continuous positive airway pressure reduces blood pressure (BP), but adherence is often suboptimal, and the benefit beyond management of conventional risk factors is uncertain. Since intermittent hypoxemia may underlie cardiovascular sequelae of sleep apnea, these researchers evaluated the effects of nocturnal supplemental O2 and CPAP on markers of cardiovascular risk. They conducted a RCT in which patients with cardiovascular disease or multiple cardiovascular risk factors were recruited from cardiology practices. Patients were screened for OSA with the use of the Berlin questionnaire, and home sleep testing was used to establish the diagnosis. Participants with an AHI of 15 to 50 events per hour were randomly assigned to receive education on sleep hygiene and healthy lifestyle alone (the control group) or, in addition to education, either CPAP or nocturnal supplemental O2. Cardiovascular risk was assessed at baseline and after 12 weeks of the study treatment. The primary outcome was 24-hour mean arterial BP. Of 318 patients who underwent randomization, 281 (88 %) could be evaluated for ambulatory BP at both baseline and follow-up. On average, the 24-hour mean arterial BP at 12 weeks was lower in the group receiving CPAP than in the control group (-2.4 mm Hg; 95 % CI: -4.7 to -0.1; p = 0.04) or the group receiving supplemental O2 (-2.8 mm Hg; 95 % CI: -5.1 to -0.5; p = 0.02). There was no significant difference in the 24-hour mean arterial BP between the control group and the group receiving oxygen. A sensitivity analysis performed with the use of multiple imputation approaches to assess the effect of missing data did not change the results of the primary analysis. The authors concluded that in patients with cardiovascular disease or multiple cardiovascular risk factors, the treatment of OSA with CPAP, but not nocturnal supplemental O2, resulted in a significant reduction in BP.
Furthermore, UpToDate reviews on "Management of obstructive sleep apnea in adults" (Kryger and Malhotra, 2014) and "Overview of obstructive sleep apnea in adults" (Strohl, 2014) do not mention oxygen as a therapeutic option.
In a systematic review and meta-analysis, Ruan et al (2023) examined the effectiveness of supplemental O2 therapy and high-flow nasal cannula (HFNC) therapy in patients with OSA in different clinical settings to evaluate its use in surgical patients in the post-operative setting. These investigators carried out a systematic search on Medline and other databases from 1946 to December 16, 2021. Title and abstract screening were performed independently, and the lead investigators resolved conflicts. Meta-analyses were carried out using a random-effects model and were presented as MD and SMD with 95 % CIs. These were calculated using RevMan 5.4. A total of 1,395 and 228 OSA patients underwent O2 therapy and HFNC therapy, respectively. Measurements included AHI, oxyhemoglobin saturation (SpO2), cumulative time with SPO2 of less than 90 % (CT90). A total of 27 O2 therapy studies were included in the review, with 10 RCTs, 7 randomized cross-overs, 7 non-randomized cross-overs, and 3 prospective cohorts. Pooled analyses showed that O2 therapy significantly reduced AHI by 31 % and increased SpO2 by 5 % versus baseline, and CPAP significantly reduced AHI by 84 %, and increased SpO2 by 3 % versus baseline. CPAP was 53 % more effective in reducing AHI than O2 therapy, but both treatments had similar effectiveness in increasing SpO2. A total of 9 HFNC studies were included in the review, with 5 prospective cohorts, 3 randomized cross-overs, and 1 RCT. Pooled analyses showed that HFNC therapy significantly reduced AHI by 36 % but did not substantially increase SpO2. The authors concluded that O2 therapy effectively decreased AHI and increased SpO2 in patients with OSA. CPAP was more effective in reducing AHI than O2 therapy; and HFNC therapy was effective in reducing AHI. Although both O2 therapy and HFNC therapy effectively reduced AHI, more research is needed to draw conclusions on clinical outcomes.
Acute Myocardial Infarction
Fu and colleagues (2017) stated that potential benefits or risks of oxygen inhalation for patients with acute myocardial infarction (MI) are not fully understood. In a systematic review and meta-analysis, these researchers evaluated the safety and effectiveness of oxygen therapy for patients with acute MI. They searched RCTs systematically in PubMed, Embase, Web of Science and Cochrane Library up to June 2016; RCTs that estimated the safety and effectiveness of oxygen therapy for patients with acute MI were identified by 2 independent reviewers. The primary outcomes were short-term mortality and recurrent rate of MI, and the secondary outcomes were arrhythmia incidence and pain incidence; RRs and 95 % CIs were used to measure the pooled data. A total of 5 RCTs were in accordance with inclusion criteria and were included in this meta-analysis. Compared with no oxygen group, the oxygen group did not significantly reduce short-term death (RR: 1.08, 95 % CI: 0.31 to 3.74), and there was moderate heterogeneity (I2 = 50.8 %, p < 0.107) among studies. These investigators found a significant increase in the rate of recurrent MI (RR: 6.73, 95 % CI: 1.80 to 25.17, I2 = 0.0 %, p = 0.598) in the oxygen group. The oxygen group did not have a significant reduction in arrhythmia (RR: 1.12, 95 % CI: 0.91 to 1.36; I2 = 46.2 %, p < 0.156) or pain (RR: 0.97, 95 % CI: 0.91 to 1.04; I2 = 7.2 %, p = 0.340). The authors concluded that oxygen inhalation did not benefit patients with acute MI with normal oxygen saturation; and it may increase the rate of recurrent MI. They stated that high quality trials with larger sample sizes are needed.
Hofmann and associates (2017) noted that the clinical effect of routine oxygen therapy in patients with suspected acute MI who do not have hypoxemia at baseline is uncertain. In this registry-based randomized clinical trial, these researchers used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected MI and an oxygen saturation of 90 % or higher were randomly assigned to receive either supplemental oxygen (6 L/min for 6 to 12 hours, delivered through an open face mask) or ambient air. A total of 6,629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99 % among patients assigned to oxygen and 97 % among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9 %) in the oxygen group, as compared with 254 patients (7.7 %) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng/Lin the oxygen group and 983.0 ng/L in the ambient-air group. The primary end-point of death from any cause within 1 year after randomization occurred in 5.0 % of patients (166 of 3,311) assigned to oxygen and in 5.1 % of patients (168 of 3,318) assigned to ambient air (hazard ratio [HR], 0.97; 95 % CI: 0.79 to 1.21; p = 0.80). Re-hospitalization with MI within 1 year occurred in 126 patients (3.8 %) assigned to oxygen and in 111 patients (3.3 %) assigned to ambient air (HR, 1.13; 95 % CI: 0.88 to 1.46; p = 0.33). The results were consistent across all pre-defined subgroups. The authors concluded that routine use of supplemental oxygen in patients with suspected MI who did not have hypoxemia was not found to reduce 1-year all-cause mortality.
Acute Respiratory Failure in Immunocompromised Individuals
Huang and colleagues (2017) evaluated the effect of high-flow nasal cannula oxygen therapy (HFNC) compared with other oxygen technique for the treatment of acute respiratory failure in immunocompromised individuals. These investigators searched Cochrane library, Embase, PubMed databases before August 15, 2017 for eligible articles. A meta-analysis was performed for measuring short-term mortality (defined as intensive care unit [ICU], hospital or 28-days mortality) and intubation rate as the primary outcomes, and length of stay (LOS) in ICU as the secondary outcome. They included 7 studies involving 667 patients. Use of HFNC was significantly associated with a reduction in short-term mortality (RR 0.66; 95 % CI: 0.52 to 0.84, p = 0.0007) and intubation rate (RR 0.76, 95 % CI: 0.64 to 0.90; p = 0.002). In addition, HFNC did not significantly increase LOS in ICU (MD 0.15 days; 95 % CI: -2.08 to 2.39; p = 0.89). The authors concluded that the findings of the current meta-analysis suggested that the use of HFNC significantly improved outcomes of acute respiratory failure in immunocompromised patients. However, due to the quality of the included studies, further adequately powered RCTs are needed to confirm these findings.
In a Cochrane review, Corley and associates (2017) assessed the safety and effectiveness of HFNC compared with comparator interventions in terms of treatment failure, mortality, adverse events (AEs), duration of respiratory support, hospital and ICU-LOS, respiratory effects, patient-reported outcomes, and costs of treatment. These investigators searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3), Medline, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Web of Science, proceedings from four conferences, and clinical trials registries; and they hand-searched reference lists of relevant studies. They conducted searches from January 2000 to March 2016 and re-ran the searches in December 2016. They added 4 new studies of potential interest to a list of "Studies awaiting classification" and incorporated them into formal review findings during the review update. These researchers included randomized controlled studies with a parallel or cross-over design comparing HFNC use in adult ICU patients versus other forms of non-invasive respiratory support (low-flow oxygen via nasal cannulae or mask, CPAP, and bi-level positive airway pressure (BiPAP)). Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. They included 11 studies with 1,972 participants. Participants in 6 studies had respiratory failure, and in 5 studies required oxygen therapy after extubation; 10 studies compared HFNC versus low-flow oxygen devices; 1 of these also compared HFNC versus CPAP, and another compared HFNC versus BiPAP alone. Most studies reported randomization and allocation concealment inadequately and provided inconsistent details of outcome assessor blinding. These researchers did not combine data for CPAP and BiPAP comparisons with data for low-flow oxygen devices; study data were insufficient for separate analysis of CPAP and BiPAP for most outcomes. For the primary outcomes of treatment failure (1,066 participants; 6 studies) and mortality (755 participants; 3 studies), investigators found no differences between HFNC and low-flow oxygen therapies (RR, Mantel-Haenszel (MH), random-effects 0.79, 95 % CI: 0.49 to 1.27; and RR, MH, random-effects 0.63, 95 % CI: 0.38 to 1.06, respectively). These investigators used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to down-grade the certainty of this evidence to low because of study risks of bias and different participant indications. Reported AEs included nosocomial pneumonia, oxygen desaturation, visits to general practitioner for respiratory complications, pneumothorax, acute pseudo-obstruction, cardiac dysrhythmia, septic shock, and cardiorespiratory arrest. However, single studies reported AEs, and the authors could not combine these findings; 1 study reported fewer episodes of oxygen desaturation with HFNC but no differences in all other reported AEs. These researchers down-graded the certainty of evidence for AEs to low because of limited data. Researchers noted no differences in ICU-LOS(mean difference (MD), inverse variance (IV), random-effects 0.15, 95 % CI: -0.03 to 0.34; 4 studies; 770 participants), and they down-graded quality to low because of study risks of bias and different participant indications. They found no differences in oxygenation variables: partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) (MD, IV, random-effects 7.31, 95 % CI: -23.69 to 41.31; 4 studies; 510 participants); PaO2 (MD, IV, random-effects 2.79, 95 % CI: -5.47 to 11.05; 3 studies; 355 participants); and oxygen saturation (SpO2) up to 24 hours (MD, IV, random-effects 0.72, 95 % CI: -0.73 to 2.17; 4 studies; 512 participants). Data from 2 studies showed that oxygen saturation measured after 24 hours was improved among those treated with HFNC (MD, IV, random-effects 1.28, 95 % CI: 0.02 to 2.55; 445 participants), but this difference was small and was not clinically significant. Along with concern about risks of bias and differences in participant indications, review authors noted a high level of unexplained statistical heterogeneity in oxygenation effect estimates, and they down-graded the quality of evidence to very low. Meta-analysis of 3 comparable studies showed no differences in carbon dioxide clearance among those treated with HFNC (MD, IV, random-effects -0.75, 95 % CI: -2.04 to 0.55; 3 studies; 590 participants); 2 studies reported no differences in atelectasis; the authors did not combine these findings. Data from 6 studies (867 participants) comparing HFNC versus low-flow oxygen showed no differences in respiratory rates up to 24 hours according to type of oxygen delivery device (MD, IV, random-effects -1.51, 95 % CI: -3.36 to 0.35), and no difference after 24 hours (MD, IV, random-effects -2.71, 95 % CI: -7.12 to 1.70; 2 studies; 445 participants). Improvement in respiratory rates when HFNC was compared with CPAP or BiPAP was not clinically important (MD, IV, random-effects -0.89, 95 % CI: -1.74 to -0.05; 2 studies; 834 participants). Results showed no differences in patient-reported measures of comfort according to oxygen delivery devices in the short-term (MD, IV, random-effects 0.14, 95 % CI: -0.65 to 0.93; 3 studies; 462 participants) and in the long-term (MD, IV, random-effects -0.36, 95 % CI: -3.70 to 2.98; 2 studies; 445 participants); these researchers down-graded the certainty of this evidence to low; 6 studies measured dyspnea on incomparable scales, yielding inconsistent study data. No study in this review provided data on positive end-expiratory pressure (PEEP) measured at the pharyngeal level, work of breathing, or cost comparisons of treatment. The authors were unable to demonstrate whether HFNC was a more safe or effective oxygen delivery device compared with other oxygenation devices in adult ICU patients. Meta-analysis could be performed for few studies for each outcome, and data for comparisons with CPAP or BiPAP were very limited. In addition, they identified some risks of bias among included studies, differences in patient groups, and high levels of statistical heterogeneity for some outcomes, leading to uncertainty regarding the results of this analysis. Thus, they stated that evidence is insufficient to show whether HFNC provided safe and effective respiratory support for adult ICU patients.
Acute Stroke
In a single-blind, randomized clinical trial, Roffe and colleagues (2017) examined if routine prophylactic low-dose oxygen therapy was more effective than control oxygen administration in reducing death and disability at 90 days, and if so, whether oxygen given at night only, when hypoxia is most frequent, and oxygen administration is least likely to interfere with rehabilitation, was more effective than continuous supplementation. A total of 8,003 adults with acute stroke were enrolled from 136 participating centers in the United Kingdom within 24 hours of hospital admission if they had no clear indications for or contraindications to oxygen treatment (first patient enrolled April 24, 2008; last follow-up January 27, 2015). Participants were randomized 1:1:1 to continuous oxygen for 72 hours (n = 2,668), nocturnal oxygen (21:00 to 07:00 hours) for 3 nights (n = 2,667), or control (oxygen only if clinically indicated; n = 2,668). Oxygen was given via nasal tubes at 3 L/min if baseline oxygen saturation was 93 % or less and at 2 L/min if oxygen saturation was greater than 93 %. The primary outcome was reported using the modified Rankin Scale (mRS) score (disability range, 0 [no symptoms] to 6 [death]; minimum clinically important difference, 1 point), assessed at 90 days by postal questionnaire (participant aware, assessor blinded). The mRS score was analyzed by ordinal logistic regression, which yielded a common odds ratio (OR) for a change from 1 disability level to the next better (lower) level; or greater than 1.00 indicates improvement. A total of 8,003 patients (4,398 (55 %) men; mean [SD] age of 72 [13] years; median National Institutes of Health Stroke Scale (NIHSS) score of 5; mean baseline oxygen saturation, 96.6 %) were enrolled. The primary outcome was available for 7,677 (96 %) participants. The unadjusted OR for a better outcome (calculated via ordinal logistic regression) was 0.97 (95 % CI: 0.89 to 1.05; p = 0.47) for oxygen versus control, and the OR was 1.03 (95 % CI: 0.93 to 1.13; p = 0.61) for continuous versus nocturnal oxygen. No subgroup could be identified that benefited from oxygen. At least 1 serious adverse event (AE) occurred in 348 (13.0 %) participants in the continuous oxygen group, 294 (11.0 %) in the nocturnal group, and 322 (12.1 %) in the control group. No significant harms were identified. The authors concluded that among non-hypoxic patients with acute stroke, the prophylactic use of low-dose oxygen supplementation did not reduce death or disability at 3 months. They stated that these findings did not support low-dose oxygen in this setting.
High-Flow Nasal Cannula Oxygen Therapy Following Planned Extubation
Huang and co-workers (2018) conducted a systematic review and meta-analysis of RCTs to examined the effect of high-flow nasal cannula (HFNC) on re-intubation in adult patients. Ovid Medline, Embase, and Cochrane Database of Systematic Reviews were searched up to November 1, 2016, for RCTs comparing HFNC versus conventional oxygen therapy (COT) or non-invasive ventilation (NIV) in adult patients after extubation. The primary outcome was re-intubation rate, and the secondary outcomes included complications, tolerance and comfort, time to re-intubation, LOS, and mortality. Dichotomous outcomes were presented as RR with 95 % CIs and continuous outcomes as weighted mean difference (WMD) and 95% CIs. The random effects model was used for data pooling. A total of 7 RCTs involving 2,781 patients were included in the analysis. The HFNC had a similar re-intubation rate compared to either COT (RR, 0.58; 95 % CI: 0.21 to 1.60; p = 0.29; 5 RCTs, n = 1,347) or NIV (RR, 1.11; 95 % CI: 0.88 to 1.40; p = 0.37; 2 RCTs, n = 1,434). In subgroup of critically ill patients, the HFNC group had a significantly lower re-intubation rate compared to the COT group (RR, 0.35; 95 % CI: 0.19 to 0.64; p = 0.0007; 2 RCTs, n = 632; interaction p = 0.07 compared to post-operative subgroup). Qualitative analysis suggested that HFNC might be associated with less complications and improved patient's tolerance and comfort. The HFNC might not delay re-intubation. The authors concluded that the evidence suggested that COT may still be the first-line therapy in post-operative patients without acute respiratory failure (ARF). However, in critically ill patients, HFNC may be a potential alternative respiratory support to COT and NIV, with the latter often associating with patient intolerance and requiring a monitored setting. These investigators stated that because required information size was not reached, further high-quality studies are needed to confirm these findings.
Zhu and colleagues (2019) noted that the effect of HFNC therapy in patients after planned extubation remains inconclusive. These researchers performed a meta-analysis to quantify the benefits of HFNC for patients after planned extubation by examining post-extubation respiratory failure and other outcomes. They searched Medline, Embase, Web of Science, and the Cochrane Library from inception to August 2018; 2 researchers screened studies and collected the data independently; RCTs and cross-over studies were included. The main outcome was post-extubation respiratory failure. A total of 10 studies (7 RCTs and 3 cross-over studies; HFNC group: 856 patients; COT group: 852 patients) were included. Compared with COT, HFNC may significantly reduce post-extubation respiratory failure (RR, 0.61; 95 % CI: 0.41 to 0.92; z = 2.38; p = 0.02) and respiratory rates (standardized mean differences (SMD), - 0.70; 95 % CI: - 1.16 to - 0.25; z = 3.03; p = 0.002) and increase PaO2 (SMD, 0.30; 95 % CI: 0.04 to 0.56; z = 2.23; p = 0.03). There were no significant differences in re-intubation rate, length of ICU and hospital stay, comfort score, PaCO2, mortality in ICU and hospital, and severe AEs between HFNC and COT group. The authors concluded that the findings of this meta-analysis demonstrated that compared with COT, HFNC may significantly reduce post-extubation respiratory failure and respiratory rates, increase PaO2, and be safely administered in patients after planned extubation. Moreover, these researchers stated that further large-scale, multi-center studies are needed to confirm these findings.
The authors stated that this meta-analysis had several drawbacks. First, it involved a heterogeneous population of patients among the included studies, which could affect these findings. To address this problem, subgroup analyses and multiple sensitivity analysis were performed; and the subgroup findings remained consistent with the overall findings. Multiple sensitivity analysis including changing effect models, excluding the high-risk bias study and/or early termination studies, did not change the overall results. Thus, these investigators believed the results were credible. Furthermore, the heterogeneous population of patients in this meat-analysis enabled their findings to have a general external validity in mixed populations of critically ill patients. Second, the duration of HFNC varied among the included studies; their previous study showed that HFNC therapy might lower the rate of escalation of respiratory support and the intubation rate when ARF patients were treated with HFNC for greater than or equal to 24 hours. However, a subgroup analysis of the present study did not find any interactions with regard to the duration of HFNC. Further studies comparing the effect of duration in HFNC treatment in patients after planned extubation are needed. Third, among the included studies, FiO2 was titrated according to SpO2 or SaO2. These researchers have reviewed all the studies included in this meta-analysis. Unexpectedly, except for the studies by Song and Tiruvoipati, the clear FiO2 values in these studies were not well-reported. Subgroup analysis with regard to FiO2 was not performed. Finally, the authors included 3 cross-over studies in the present analysis and cross-over studies are limited by nature. Hence, these investigators used the GRADE Guideline Development Tool to evaluate the quality of evidence that showed equal quality levels between cross-over studies and randomized studies, showing that the findings from the cross-over studies should also be seriously considered.
In a systematic review and meta-analysis, Lu and associates (2019) examined the effect of HFNC versus COT on the re-intubation rate, rate of escalation of respiratory support and clinical outcomes in post-extubation adult surgical patients. PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Index and Wan fang databases were searched up to August 2018. Studies in post-operative adult surgical patients (greater than or equal to 18 years of age), receiving HFNC or COT applied immediately after extubation that reported re-intubation, escalation of respiratory support, post-operative pulmonary complications (PPCs) and mortality were eligible for inclusion. The following data were extracted from the included studies: first author's name, year of publication, study population, country of origin, study design, number of patients, patients' baseline characteristics and outcomes. Associations were evaluated using RR and 95 % CIs. This meta-analysis included 10 studies (1,327 patients); HFNC significantly reduced the reintubation rate (RR 0.38, 95 % CI: 0.23 to 0.61, p < 0.0001) and rate of escalation of respiratory support (RR 0.43, 95 % CI: 0.26 to 0.73, p = 0.002) in post-extubation surgical patients compared with COT. There were no differences in the incidence of PPCs (RR 0.87, 95 % CI: 0.70 to 1.08, p = 0.21) or mortality (RR 0.45, 95 % CI: 0.16 to 1.29, p = 0.14). The authors concluded that HFNC was associated with a significantly lower re-intubation rate and rate of escalation of respiratory support compared with COT in post-extubation adult surgical patients, however, there was no difference in the incidence of PPCs or mortality. These researchers stated that more well-designed, large RCTs are needed to determine the subpopulation of patients who are most likely to benefit from HFNC therapy.
The authors stated that this systematic review and meta-analysis had several drawbacks. First, not all included studies examined re-intubation rates and respiratory support escalation as primary end-points, and most of the included studies were single-center studies. Second, there were differences in the timing and duration of HFNC treatment and length of follow-up in the included studies. Third, the sample size was small; 3 out of 10 studies were non-RCTs, including less than 50 patients each. These limitations represented potential sources of bias and heterogeneity.
Reduction of Transfusion-Related Adverse Events in Pregnant Women with Sickle Cell Disease
Ribeil and colleagues (2018) noted that sickle cell disease (SCD) in pregnancy can be associated with adverse maternal and perinatal outcomes. Furthermore, complications of SCD can be aggravated by pregnancy. Optimal prenatal care aims to decrease the occurrence of maternal and fetal complications. In a retrospective, French, 2-center study, these investigators compared 2 care strategies for pregnant women with SCD over 2 time-periods. In the first study period (2005 to 2010), women were systematically offered prophylactic transfusions. In the second study period (2011 to 2014), a targeted transfusion strategy was applied whenever possible, and home-based prophylactic nocturnal oxygen therapy was offered to all the pregnant women. The 2 periods did not differ significantly in terms of the incidence of vaso-occlusive events. Maternal mortality, perinatal mortality, and obstetric complication rates were also similar in the 2 periods, as was the incidence of post-transfusion complications (6.1 % in 2005 to 2010 and 1.3 % in 2011 to 2014, p = 0.15), although no de-novo allo-immunizations or delayed hemolysis transfusion reactions were observed in the second period. The authors concluded that the findings of this preliminary, retrospective study indicated that targeted transfusion plus home-based prophylactic nocturnal oxygen therapy was safe and may decrease transfusion requirements and transfusion-associated complications. They stated that the use of prophylactic home oxygen therapy in SCD appeared promising as their patients currently request this new therapeutic option (despite its constraints); the preliminary results in previous studies have been positive; and a pilot study of morbidity prevention in SCD by overnight supplementary oxygen has recently been initiated. These researchers stated that their forthcoming prospective multi-center RCT should enable them to establish a severity score and therefore adapt the therapeutic strategy according to a patient's risk factors.
The authors stated that no definitive conclusion could be drawn from this retrospective study of 2 concomitant changes in their treatment strategy (i.e., targeted transfusion and prophylactic oxygen therapy). The methodological drawback of retrospective studies was highlighted in a recent meta‐analysis by Malinowski et al. Considering this limitation, these researchers have set up a prospective, multi-center RCT of prophylactic oxygen therapy during SCD pregnancies. In fact, these investigators hypothesize that prophylactic oxygen therapy relieves the symptoms of SCD (particularly during pregnancy). Accordingly, they intend to examine if an independent effect on treatment outcomes exists in this high‐risk medical setting. The study will investigate whether prophylactic oxygen therapy will decrease the transfusion requirement and the incidence of severe post‐transfusion complications without increasing the incidence of vaso‐occlusive crises or obstetric complications. If this end-point is met, prophylactic oxygen therapy may be of major value, especially in regions with sub‐optimal transfusion safety. All the pregnant women with SCD in this ongoing RCT will undergo oximetry measurements for 2 consecutive nights so that these researchers can establish whether the results are significant in a hypoxic subgroup only.
Treatment of Pediatric Seizures
There are a lack of published clinical studies of the effectiveness of home oxygen as a treatment for epilepsy in children. UpToDate reviews on "Seizures and epilepsy in children: Initial treatment and monitoring" (Wilfong, 2018a) and "Seizures and epilepsy in children: Refractory seizures and prognosis" (Wilfong, 2018b) do not mention oxygen as a therapeutic option.
High-Flow Nasal Oxygen
Alnajada and associates (2021) noted that acute type II respiratory failure (AT2RF) is characterized by high carbon dioxide levels (PaCO2 greater than 6kPa). Non-invasive ventilation (NIV), the current standard of care (SOC), has a high failure rate. High-flow nasal therapy (HFNT) has potential additional benefits such as CO2 clearance, the ability to communicate and comfort. In a systematic review, these researchers examined if HFNT in AT2RF improves PaCO2, clinical as well as patient-centered outcomes; and evaluated potential harms. They searched Embase, Medline and CENTRAL (January 1999 to January 2021); RCTs) and cohort studies comparing HFNT with low-flow nasal oxygen (LFNO) or NIV were included. Two authors independently examined studies for eligibility, data extraction and risk of bias. They used Cochrane risk of bias tool for RCTs and Ottawa-Newcastle scale for cohort studies. From 727 publications reviewed, 4 RCTs and 1 cohort study (n = 425) were included. In 3 trials of HFNT versus NIV, comparing PaCO2 (kPa) at last follow-up time-point, there was a significant reduction at 4 hours (1 RCT; HFNT median of 6.7, inter-quartile range [IQR] of 5.6 to 7.7 versus NIV median of 7.6, IQR of 6.3 to 9.3) and no significant difference at 24-hours or 5 days. Comparing HFNT with LFNO, there was no significant difference at 30-mins. There was no difference in intubation or mortality. The authors concluded that this systematic review identified a small number of studies with low to very-low certainty of evidence. A reduction of PaCO2 at an early time-point of 4 hours post-intervention was demonstrated in 1 small RCT. Significant drawbacks of the included studies were lack of adequately powered outcomes and clinically relevant time-points and small sample size. Based on the findings of this systematic review, these investigators could not recommend the use of HFNT as the initial management strategy for AT2RF and trials adequately powered to detect clinical and patient-relevant outcomes are urgently needed.
Lewis and co-workers (2021) noted that HFNC delivers high flows of blended humidified air and oxygen via wide-bore nasal cannulae; and may be useful in providing respiratory support for adults experiencing ARF, or at risk of ARF, in the ICU. This is an update of an earlier version of the review. These researchers examined the effectiveness of HFNC compared to standard oxygen therapy, or NIV or non-invasive positive pressure ventilation (NIPPV), for respiratory support in adults in the ICU. They searched CENTRAL, Medline, Embase, CINAHL, Web of Science, and the Cochrane COVID-19 Register (April 17, 2020), clinical trial registers (April 6, 2020) and conducted forward and backward citation searches. These investigators included RCTs with a parallel-group or cross-over design comparing HFNC use versus other types of non-invasive respiratory support (standard oxygen therapy via nasal cannulae or mask; or NIV or NIPPV, which included CPAP and BiPAP) in adults admitted to the ICU. They used standard methodological procedures as expected by Cochrane. These researchers included 31 studies (22 parallel-group and 9 cross-over designs) with 5,136 subjects; this update included 20 new studies. Twenty-one studies compared HFNC with standard oxygen therapy, and 13 compared HFNC with NIV or NIPPV; 3 studies included both comparisons. They found 51 ongoing studies (estimated 12,807 subjects), and 19 studies awaiting classification for which these investigators could not ascertain study eligibility information. In 18 studies, treatment was initiated after extubation. In the remaining studies, participants were not previously mechanically ventilated. HFNC versus standard oxygen therapy: HFNC may lead to less treatment failure as indicated by escalation to alternative types of oxygen therapy (RR 0.62, 95 % CI: 0.45 to 0.86; 15 studies, 3,044 participants; low-certainty evidence). HFNC probably made little or no difference in mortality when compared with standard oxygen therapy (RR 0.96, 95 % CI: 0.82 to 1.11; 11 studies, 2,673 participants; moderate-certainty evidence). HFNC probably resulted in little or no difference to cases of pneumonia (RR 0.72, 95 % CI: 0.48 to 1.09; 4 studies, 1,057 participants; moderate-certainty evidence), and these researchers were uncertain of its effect on nasal mucosa or skin trauma (RR 3.66, 95 % CI: 0.43 to 31.48; 2 studies, 617 participants; very low-certainty evidence). These investigators found low-certainty evidence that HFNC may make little or no difference to the ICU LOS according to the type of respiratory support used (MD 0.12 days, 95 % CI: -0.03 to 0.27; 7 studies, 1,014 participants). They were uncertain whether HFNC made any difference to the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) within 24 hours of treatment (MD 10.34 mmHg, 95 % CI: -17.31 to 38; 5 studies, 600 participants; very low-certainty evidence). They were uncertain whether HFNC made any difference to short-term comfort (MD 0.31, 95 % CI: -0.60 to 1.22; 4 studies, 662 participants, very low-certainty evidence), or to long-term comfort (MD 0.59, 95 % CI: -2.29 to 3.47; 2 studies, 445 participants, very low-certainty evidence). HFNC versus NIV or NIPPV: These investigators found no evidence of a difference between groups in treatment failure when HFNC were used post-extubation or without prior use of mechanical ventilation (RR 0.98, 95 % CI: 0.78 to 1.22; 5 studies, 1,758 participants; low-certainty evidence), or in-hospital mortality (RR 0.92, 95 % CI: 0.64 to 1.31; 5 studies, 1,758 participants; low-certainty evidence). They were very uncertain about the effect of using HFNC on incidence of pneumonia (RR 0.51, 95 % CI: 0.17 to 1.52; 3 studies, 1,750 participants; very low-certainty evidence), and HFNC may result in little or no difference to barotrauma (RR 1.15, 95 % CI: 0.42 to 3.14; 1 study, 830 participants; low-certainty evidence). HFNC may make little or no difference to the ICU LOS (MD -0.72 days, 95 % CI: -2.85 to 1.42; 2 studies, 246 participants; low-certainty evidence). The ratio of PaO2/FiO2 may be lower up to 24 hours with HFNC use (MD -58.10 mmHg, 95 % CI: -71.68 to -44.51; 3 studies, 1,086 participants; low-certainty evidence). They were uncertain whether HFNC improved short-term comfort when measured using comfort scores (MD 1.33, 95 % CI: 0.74 to 1.92; 2 studies, 258 participants) and responses to questionnaires (RR 1.30, 95 % CI: 1.10 to 1.53; 1 study, 168 participants); evidence for short-term comfort was very low certainty. No studies reported on nasal mucosa or skin trauma. The authors concluded that HFNC may lead to less treatment failure when compared to standard oxygen therapy, but probably made little or no difference to treatment failure when compared to NIV or NIPPV. For most other review outcomes, these researchers found no evidence of a difference in effect. However, the evidence was often of low or very-low certainty. These investigators found a large number of ongoing studies, which could increase the certainty or may alter the direction of these effects.
Qaseem and colleagues (2021) stated that the American College of Physicians (ACP) developed guidelines to provide clinical recommendations on the appropriate use of high-flow nasal oxygen (HFNO) in hospitalized patients for initial or post-extubation management of acute respiratory failure. It is based on the best available evidence on the benefits and harms of HFNO, taken in the context of costs and patient values and preferences. The ACP Clinical Guidelines Committee based these recommendations on a systematic review on the safety and effectiveness of HFNO. The patient-centered health outcomes evaluated included all-cause mortality, hospital LOS, 30-day hospital re-admissions, hospital-acquired pneumonia, days of intubation or re-intubation, ICU admission and ICU transfers, patient comfort, dyspnea, delirium, barotrauma, compromised nutrition, gastric dysfunction, functional independence at discharge, discharge disposition, and skin breakdown. This guideline was developed using the GRADE method.
Recommendation 1a: ACP suggests that clinicians use HFNO rather than non-invasive ventilation in hospitalized adults for the management of acute hypoxemic respiratory failure (Conditional recommendation; low-certainty evidence).
Recommendation 1b: ACP suggests that clinicians use HFNO rather than conventional oxygen therapy for hospitalized adults with post-extubation acute hypoxemic respiratory failure (Conditional recommendation; low-certainty evidence).
Home Oxygen for Bronchiolitis
Lawrence et al (2022) stated that bronchiolitis is the leading cause of pediatric hospital admissions. Hospital-at-home (HAH) delivers hospital-level care at home, relieving pressure on the hospital system. In a systematic review, these investigators examined the feasibility, acceptability, and safety of HAH for bronchiolitis, and evaluated the cost-impact to hospitals and society. Data sources included Ovid Medline, Embase, PubMed, Cochrane Library, CINAHL, and Web of Science. Studies (RCTs, retrospective audits, prospective, observational trials) of infants with bronchiolitis receiving HAH (oxygen, nasogastric feeding, remote monitoring) were selected for analysis. Studies were limited to English language since 2000. These researchers reviewed all studies in duplicate for inclusion, data extraction, and risk of bias. A total of 10 studies met inclusion criteria, all for home oxygen therapy (HOT). One abstract on nasogastric feeding did not meet full inclusion criteria. No studies on remote monitoring were found. HOT appeared feasible in terms of uptake (70 % to 82 %) and successful completion, both at altitude and sea-level. Caregiver acceptability was reported in 2 qualitative studies. There were 7 reported AEs (0.6 %) with 0 mortality in 1,257 patients. Cost studies showed evidence of savings, although included costs to hospitals only. The authors concluded that evidence exists to support HOT as feasible, acceptable, and safe. Evidence of cost-effectiveness remains limited. These researchers stated that further investigation is needed to understand the relevant impact of HAH versus alternative interventions to reduce oxygen prescribing. Other models of care examining nasogastric feeding support and remote monitoring should be explored. These investigators stated that the drawbacks of this systematic review were that the conclusions were limited by a small number of published studies (n = 10) with heterogenous study design and quality; and the lack of adequately powered RCTs. Cost studies found evidence of cost savings; however, they included hospital costs only, omitting costs to families and the costs of the home program; thus, limiting the ability to draw conclusions regarding the cost-effectiveness of HAH.
Home Oxygen for Chronic Obstructive Pulmonary Disease
Lacasse et al (2022) noted that long-term oxygen therapy (LTOT) improves survival in patients with COPD and severe hypoxemia; however, the best method of management of moderate hypoxemia not qualifying for LTOT (including isolated nocturnal desaturation) is uncertain. In a systematic review and meta-analysis, these investigators examined the effect of home oxygen (either LTOT or nocturnal oxygen therapy) on overall survival (OS) in patients with COPD and moderate hypoxemia. They searched Medline, Embase, the Cochrane Central Register of Controlled Trials, CINHAL, and Web of Science from database inception to January 13, 2022, for parallel group randomized trials of long-term or nocturnal oxygen in patients with COPD and moderate daytime hypoxemia or isolated nocturnal desaturation, or both. Control groups received usual care or ambient air through sham concentrators (placebo) throughout the study period. The primary outcome of interest was 3-year mortality. Cross-over trials and trials of oxygen in severe hypoxemia were excluded. Two reviewers applied inclusion and exclusion criteria to titles and abstracts and screened the full-text articles and reference lists of relevant studies. Aggregate data were extracted manually in duplicate using structured data collection forms. Methodological quality was assessed using the Cochrane Risk of Bias tool. Random-effects meta-analysis was used to pool individual studies. These researchers considered the minimal clinically important difference for home oxygen to be a relative risk reduction in mortality at 3-year follow-up of 30 % to 40 %. These researchers identified 2,192 studies and screened 1,447 after removal of duplicates, of which 161 were subjected to full-text screening, and 6 were identified as being eligible for inclusion. These 6 randomized trials were published between 1992 and 2020 and the quality of evidence was high. In the primary meta-analysis (5 trials; 1,002 patients), these investigators found the effect of home oxygen in reducing 3-year mortality to be small or absent (RR 0.91 [95 % CI: 0.72 to 1.16]; τ2 = 0.00), hence the lower limit of the 95 % CI did not meet the pre-specified minimal clinically important difference. The authors concluded that the findings of this meta-analysis suggested that home oxygen probably made little or no difference to 3-year mortality in patients with COPD and moderate hypoxemia. The data do not support the widespread use of home oxygen in this patient population.
High-Flow Nasal Oxygen Versus Standard Oxygen Therapy on Length of Hospital Stay in Hospitalized Children with Acute Hypoxemic Respiratory Failure
Franklin et al (2023) stated that nasal high-flow O2 therapy in infants with bronchiolitis and hypoxia has been shown to reduce the requirement to escalate care. The effectiveness of high-flow O2 therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure without bronchiolitis is unknown. In a randomized, multi-center study, these researchers examined the effect of early high-flow O2 therapy versus standard O2 therapy in children with acute hypoxemic respiratory failure. This trial was carried out at 14 metropolitan and tertiary hospitals in Australia and New Zealand, including 1,567 children aged 1 to 4 years (randomized between December 18, 2017, and March 18, 2020) requiring hospital admission for acute hypoxemic respiratory failure. The last subject follow-up was completed on March 22, 2020. Enrolled children were randomly allocated 1:1 to high-flow O2 therapy (n = 753) or standard O2 therapy (n = 764). The type of O2 therapy could not be masked, but the investigators remained blinded until the outcome data were locked. The primary outcome was hospital LOS with the hypothesis that high-flow O2 therapy would reduce hospital LOS. There were 9 secondary outcomes, including length of O2 therapy and admission to the ICU. Children were analyzed according to their randomization group. Of the 1,567 children who were randomized, 1,517 (97 %) were included in the primary analysis (median age of 1.9 years [IQR, 1.4 to 3.0 years]; 732 [46.7 %] were female) and all children completed the trial. The hospital LOS was significantly longer in the high-flow O2 group with a median of 1.77 days (IQR, 1.03 to 2.80 days) versus 1.50 days (IQR, 0.85 to 2.44 days) in the standard O2 group (adjusted HR, 0.83 [95 % CI: 0.75 to 0.92]; p < 0.001). Of the 9 pre-specified secondary outcomes, 4 showed no significant difference. The median length of O2 therapy was 1.07 days (IQR, 0.50 to 2.06 days) in the high-flow O2 group versus 0.75 days (IQR, 0.35 to 1.61 days) in the standard O2 therapy group (adjusted HR, 0.78 [95 % CI: 0.70 to 0.86]). In the high-flow O2 group, there were 94 admissions (12.5 %) to the ICU compared with 53 admissions (6.9 %) in the standard O2 group (adjusted OR, 1.93 [95 % CI: 1.35 to 2.75]). There was only 1 death and it occurred in the high-flow O2 group. The authors concluded that nasal high-flow O2 used as the initial primary therapy in children aged 1 to 4 years with acute hypoxemic respiratory failure did not significantly decrease the hospital LOS compared with standard O2 therapy.
Supra-Physiological Oxygen Administration During Surgery and Post-Operative Organ Injury
In an observational, cohort study, McIlroy et al (2022) examined if supra-physiological O2 administration during surgery is associated with lower or higher post-operative kidney, heart, and lung injury. A total of 42 medical centers across the U.S. participating in the Multicenter Perioperative Outcomes Group data registry. Participants included adult patients undergoing surgical procedures of 120 mins or longer duration with general anesthesia and endotracheal intubation who were admitted to hospital after surgery between January 2016 and November 2018. Supra-physiological O2 administration, defined as the area under the curve (AUC) of the fraction of inspired O2 above air (21 %) during minutes when the hemoglobin O2 saturation was greater than 92 %. Primary endpoints were acute kidney injury (AKI) defined using Kidney Disease Improving Global Outcomes criteria, myocardial injury defined as serum troponin of greater than 0.04 ng/ml within 72 hours of surgery, and lung injury defined using international classification of diseases hospital discharge diagnosis codes. The cohort comprised 350,647 patients with median age 59 years (IQR 46 to 69 years), 180,546 women (51.5 %), and median duration of surgery 205 mins (IQR 158 to 279 mins). Acute kidney injury was diagnosed in 19,207 of 297,554 patients (6.5 %), myocardial injury in 8,972 of 320,527 (2.8 %), and lung injury in 13,789 of 312,161 (4.4 %). The median fraction of inspired O2 was 54.0 % (IQR 47.5 % to 60.0 %), and the AUC of supra-physiological inspired O2 was 7,951 % min (5,870 to 11,107 % min), equivalent to an 80 % fraction of inspired O2 throughout a 135-min procedure, for example. After accounting for baseline co-variates and other potential confounding variables, increased O2 exposure was associated with a higher risk of AKI, myocardial injury, and lung injury. Patients at the 75th centile for the AUC of the fraction of inspired O2 had 26 % greater odds of AKI (95 % CI: 22 % to 30 %), 12 % greater odds of myocardial injury (7 % to 17 %), and 14 % greater odds of lung injury (12 % to 16 %) compared with patients at the 25th centile. Sensitivity analyses evaluating alternative definitions of the exposure, restricting the cohort, and conducting an instrumental variable analysis confirmed these observations. The authors concluded that increased intra-operative O2 exposure was associated with adverse renal, cardiac, and pulmonary outcomes in a large, diverse cohort of surgical patients. Moreover, these researchers stated that a large clinical trial to detect small but clinically significant effects on organ injury and patient-centered outcomes is needed to guide O2 administration during surgery. Furthermore, these investigators stated that residual confounding of these associations could not be excluded.
Acute Respiratory Failure in Patients Under 5 Years of Age
Rifai et al (2024) noted that acute lower respiratory infections in children under 5 years present a real challenge for diagnosis and treatment and are the 1st cause of mortality for this age group. In a retrospective study, these investigators examined the characteristics of infectious acute respiratory failure due to bronchiolitis, pulmonary infection, or severe acute asthma related to a virus or bacteria in children under 5 years old at admission to the pediatric intensive care unit (PICU), PICU management, and outcomes in order to better identify the needs of these patients. In addition, these researchers compared the characteristics and PICU management of this population depending on their age (less or more than 6 months old); and depending on the pulmonary imaging (absence or presence of an alveolar condensation on the chest X-ray or lung ultrasound [US]). This trial was carried out in 2 PICUs. Participants were children under 5 years of age; hospitalized between January 1, 2017 and December 31, 2021 due to a respiratory infection complicated by ARF. This study included 707 patients; and the median age was 3 months. On arrival, patients were oxygen-dependent with a mean fraction of inspired oxygen (FiO2) of 34 %; and 63 % required NIV. During hospitalization, more than 70 % required ventilatory support by NIV, and 10 % by tracheal intubation. Furthermore, 18 % required volemic expansion, and 4 % vasopressors. Nearly 90 % of polymerase chain reaction (PCR) tests for respiratory viruses were positive, and respiratory syncytial virus (RSV) was found in almost 2/3 of cases. Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae were frequently found. Significantly, patients aged less than 6 months needed more NIV, had less alveolar condensation, had slightly lower oxygen requirements, a less frank inflammatory syndrome, and a more frequently positive PCR for respiratory viruses. The authors highlighted similarities between patients hospitalized for lower respiratory infection in PICU in France and those in Australia or Brazil. Optimal management relied mainly on NIV, O2 therapy with FiO2 under 40 % and available antibiotics. These results lead these researchers to believe that the implementation of NIV training and equipment could aid in lowering mortality due to lower respiratory infections in children globally.
Cor Pulmonale
Thakur et al (2024) stated that pediatric cor pulmonale, characterized by right ventricular dysfunction due to chronic pulmonary hypertension, presents significant diagnostic and management challenges. These researchers addressed this complex condition's etiology, clinical presentation, diagnostic strategies, and management. Key etiological factors include congenital heart defects, chronic lung diseases, and pulmonary vascular disorders. Early diagnosis, facilitated by imaging, hemodynamic assessments, and laboratory investigations, are important for effective intervention. Pediatric cor pulmonale management entails pharmacotherapies including vasodilators, diuretics, and inotropic agents, as well as non-pharmacological interventions, including O2 therapy, mechanical ventilation, and surgical options. Long-term follow-up is crucial to monitor disease progression and adjust treatment strategies accordingly. Multi-disciplinary care involving pediatric cardiologists, pulmonologists, and critical care specialists is paramount to address the multi-faceted needs of these patients. The authors highlighted the importance of early recognition and comprehensive care, offered insights into current best practices and future research and clinical practice directions.
Glossary of Terms
| Term | Definition |
|---|---|
| Blood gas study | Oximetry test or arterial blood gas test |
| Erythrocythemia | Hematocrit greater than 56% |
Appendix
Documentation Requirements
Documentation, in the form of a prescription written by the physician, must include an estimate of the frequency, duration of use, duration of need, type of system to be used and oxygen flow rate. A physician's statement of recent hospital test results is also acceptable as well as arterial oxygen saturation obtained by pulse oximetry
International Headache Society Diagnostic Criteria for Cluster Headache
Aetna uses diagnostic criteria used by the International Headache Society to form a definitive diagnosis of CH. Therefore, the home use of oxygen to treat CH is considered medically necessary by Aetna only when furnished to members who have had at least five severe to very severe unilateral headache attacks lasting 15-180 minutes when untreated. (Intensity of pain: Degree of pain usually expressed in terms of its functional consequence and scored on a verbal 5-point scale: 0 = no pain; 1 = mild pain, does not interfere with usual activities; 2 = moderate pain, inhibits but does not wholly prevent usual activities; 3 = severe pain, prevents all activities; 4 = very severe pain. It may also be expressed on a visual analogue scale.)
The headaches must be accompanied by at least one of the following findings:
- Ipsilateral conjunctival injection and/or lacrimation; or
- Ipsilateral nasal congestion and/or rhinorrhea; or
- Ipsilateral eyelid edema; or
- Ipsilateral forehead and facial sweating; or
- Ipsilateral miosis and/or ptosis; or
- A sense of restlessness or agitation.
Qualifying Laboratory Values
Continuous Oxygen:
- Resting (awake) PaO2 less than or equal to 55 mm Hg or arterial oxygen saturation less than or equal to 88 %; or
- Resting PaO2 of 56 to 59 mm Hg or arterial oxygen saturation of 89 % at rest (awake), during sleep for at least 5 minutes, or during exercise (as described below) in the presence of any of the following:
- Dependent edema suggesting congestive heart failure
- Erythrocythemia (hematocrit greater than 56 %)
- Pulmonary hypertension or cor pulmonale, determined by measurement of pulmonary artery pressure, gated blood pool scan, echocardiogram, or "P" pulmonale on the electrocardiogram (P wave greater than 3 mm in standard leads II, III, or aVF).
-
Resting PaO2 greater than 59 mm Hg or oxygen saturation greater than 89 % only with additional documentation justifying the oxygen prescription and a summary of more conservative therapy that has failed.
Non-Continuous Oxygen:
(oxygen flow rate and number of hours per day must be specified)
- During exercise: PaO2 less than or equal to 55 mm Hg or oxygen saturation less than or equal to 88 % with a low level of exertion. In this case, provision of oxygen is considered medically necessary during exercise if it is documented that the use of oxygen improves the hypoxemia that was demonstrated during exercise when the member was breathing room air.
- During sleep:
- PaO2 less than or equal to 55 mm Hg or oxygen saturation less than or equal to 88 % for at least 5 minutes; or
- A decrease in PaO2 more than 10 mm Hg, or a decrease in arterial oxygen saturation more than 5 percent from baseline saturation, for at least 5 minutes taken during sleep associated with symptoms (e.g., impairment of cognitive processes and [nocturnal restlessness or insomnia]) or signs (e.g., cor pulmonale, "P" pulmonale on EKG, documented pulmonary hypertension and erythrocytosis) reasonably attributable to hypoxemia.
Note: All qualification studies must be done while on room air unless medically contraindicated. Documentation of blood gas values can come from the doctor's office, hospital or from an outpatient laboratory.
References
The above policy is based on the following references:
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