RCTs assessing the effectiveness of oxygen supplementation

Singhi 2012 is a report of a pilot RCT conducted in Chandigarh, India with the aim of studying the incidence of subsequent hypoxaemia in initially normoxaemic children with pneumonia and lower chest indrawing. They included patients aged two to 59 months with severe pneumonia and without hypoxaemia (SpO₂ > 90%). Patients with a known chronic systemic illness, major malformations, congenital heart disease, pneumonia secondary to aspiration/chemicals or suspected tuberculosis were excluded. Children (n = 58, three to 59 months) with pneumonia, lower chest indrawing and normoxaemia were randomly assigned to receive supplemental oxygen (nasal prongs, 1 to 2 L/min flow) (n = 29) or room air (n = 29). Vital signs and SpO₂ were monitored continuously and recorded every six hours. All patients were treated with intravenous ampicillin and gentamicin followed by oral antimicrobial therapy once they were clinically stable. Outcome variables were incidence of hypoxaemia, length of tachypnoea and lower chest indrawing. Patients who developed hypoxaemia later were similar to those who did not, except for a lower SpO₂ at enrolment

RCTs assessing the effectiveness of delivery methods

The Muhe 1997 RCT was conducted in Addis Ababa (2800 metres above sea level (MASL)), with the aim of comparing the frequency and nature of complications when nasopharyngeal catheters or nasal prongs were used to deliver oxygen. A total of 121 children between two weeks and five years of age with hypoxaemia (SpO₂ < 90%) due to acute LRTI were randomised to receive oxygen by nasopharyngeal catheters (n = 61) or nasal prongs (n = 60). Randomisation was grouped by age into three groups: two to seven weeks, eight weeks to 11 months, and 12 months to five years. Authors measured daily SaO₂ and complications (catheter blockage, nasal ulceration, nasal blockage due to drying of secretions around the catheters, abdominal distension and aspiration of gastric contents). Patients who failed to achieve adequate oxygenation with the assigned treatment were classified as primary treatment failures and the alternative treatment was then tried.

The Muhe 1998 RCT was performed in Addis Ababa (2800 MASL) with the aim of comparing the safety and effectiveness of nasal prongs compared to a modified version of the nasopharyngeal catheter (an 8 FG catheter was passed through the nose up to the same distance measured from the side of the nostril to the inner margin of the eyebrow). The study included children between two weeks and five years of age with acute LRTI associated with hypoxaemia (SpO₂ < 90%). Children were randomly assigned to receive oxygen by nasal catheter (n = 49) or nasal prongs (n = 50). Patients were stabilised on one method and then shifted to the other method to compare the oxygen required and the amount of time needed to achieve SaO₂ above 90%. Complications (nasal blockage, nasal ulcerations and nasal bleeding) were documented and recorded by the research physician.

The Weber 1995 RCT was carried out in Banjul, Gambia (27 MASL) to determine the flow rate necessary to achieve an haemoglobin oxygen saturation (SaO₂) higher than 95%. It included 118 children between seven days and five years of age with a LRTI and with SaO₂ < 90%. Children were randomly assigned to receive oxygen by nasopharyngeal catheter (n = 56) or nasal prongs (n = 62). Every two hours oxygen flow rates and SaO₂ were recorded. Nurses recorded adverse events and complications (episodic desaturations, nasal obstruction, nasal ulcerations, gastric distension and apnoea episodes) and acceptability for each delivery method. If children were not able to oxygenate with the highest flow rate of 4 L/min, they were switched to another method.

Kumar 1997 is a non‐RCT that was conducted in New Delhi at 239 MASL to compare the efficacy and acceptability of four commonly used oxygen delivery systems: head box, face mask, nasopharyngeal catheter and twin‐holed pre‐nasal catheter. They included 80 children younger than five years of age presenting with acute respiratory distress, who required oxygen to achieve a PaO₂ of 60 mmHg. Children were assigned to receive oxygen administered by all four methods for 15 minutes in a predetermined sequence. Measures of efficacy included arterial blood gas analysis and SaO₂. Acceptability in terms of child comfort was assessed by a tolerance score as perceived by the mother.

Observational studies determining the indications for oxygen therapy in children with LRTIs

From the 14 studies identified to determine the indications for oxygen therapy in children with LRTIs (i.e. which describe the oxygen saturation values or clinical signs that would indicate the need for oxygen therapy) we finally included only 13 (Basnet 2006; Duke 2002; Dyke 1995; Gutierrez 2001; Kuti 2013; Laman 2005; Lodha 2004; Lozano 1994; Onyango 1993; Reuland 1991; Smyth 1998; Usen 1999; Weber 1997). The study by Orimadegun 2013 has been assigned to the Studies awaiting classification section because the information regarding the outcomes in the LRTI subgroup of the population studied is misleading and personal communication with the trial author was unsuccessful in gathering this information. Characteristics of the observational studies included are presented in Characteristics of included studies.

The study by Reuland 1991 was conducted in Junin, the Peruvian Andes (3750 MASL) to determine the effect of respiratory infections on oxygen saturation. The prospective study included 423 children between 2 and 60 months with acute respiratory infections. Children with chronic illnesses such as asthma, congenital cardiac malformation or heart murmurs were excluded. Clinical signs and symptoms present at the time of admission were recorded by an expert physician who was blinded to the oximeter reading. SpO₂ was also measured at this time. Using two clinical categories, upper respiratory tract infection (URTI) and LRTI and balancing by age group, they determined the sensitivity, specificity and likelihood ratios (LR) for several potential indicators of hypoxaemia. The SpO₂ cut‐off was determined by studying 153 healthy children from the same population. Hypoxaemia was considered to be present if SpO₂ was > 2 standard deviations below the mean value for healthy children (2 to 11 months: SpO₂ < 84 and 12 to 60 months: SpO₂ < 86).

Onyango 1993 conducted a study in the Kenyatta National Hospital, Nairobi, Kenya (1676 MASL) in order to predict hypoxaemia based on clinical signs and symptoms present at the time of admission to the hospital. They included 256 children aged from 7 days to 36 months with LRTI. Children presenting with moderate or severe dehydration, with anaemia, central nervous system, cardiac, renal or metabolic diseases were excluded. Recorded data included respiratory rates, pulse, central cyanosis, chest retractions, grunting, nasal flaring, wheezing, crepitations or rhonchi on auscultation. SpO₂ breathing room air and a chest radiograph read by a blinded physician were taken as the gold standard for diagnosis of hypoxaemia associated with LRTI. To define the SpO₂ cut‐off point, oxygen saturation was measured with an oximeter in 87 healthy children attending the child welfare clinics (SpO₂ = mean 95.7 standard deviation (SD) 1.6%). Each clinical finding was assessed for its sensitivity and specificity in the diagnosis of hypoxaemia. Results are presented in three age strata.

The Lozano 1994 study was conducted in Bogota, Colombia (2640 MASL). It assessed the usefulness of clinical signs and symptoms in the diagnosis of radiological pneumonia or hypoxaemia (SpO₂ < 88%), or both. They included 201 children aged from seven days to 36 months, presenting with cough lasting up to seven days and whose evaluation included a chest radiograph. Children were excluded if they had cardiovascular, pulmonary, neurological or congenital defects; a chronic disease including asthma, cancer, immunosuppression and metabolic disorders; or previous episodes of wheezing. Data on symptoms and clinical signs of acute respiratory infection were obtained using a standardised questionnaire and a physical examination performed by a paediatrician. The gold standard used to calculate sensitivity and specificity for each symptom was a chest radiograph read by a blinded physician plus the oxygen saturation measured by oximeter.

The study by Dyke 1995 was undertaken in Tari, New Guinea (1600 MASL), with the aim of identifying the indications for administering oxygen based on easily recognisable signs. This study included 91 children between three months and five years with a clinical diagnosis of pneumonia. Clinical signs present at the initial evaluation (cyanosis, poor feeding, crepitations, bronchial breathing, grunting, chest indrawing, nasal flaring, drowsiness and hepatomegaly) were recorded. To establish the 'adequate' values of oxygen saturation, 100 healthy children from Tari were assessed with oximeter and hypoxaemia was defined as SpO₂ equal to or less than 85%. Sensitivity and specificity of each sign were calculated, to indicate whether hypoxaemia was present, taking the oximeter readings as the gold standard. Authors also developed regression equations to predict hypoxaemia.

Weber 1997 was a case‐control study conducted in the Royal Victoria Hospital in Banjul, Gambia at sea level, with the aim of studying the signs and symptoms indicating hypoxaemia in children with pneumonia. It included 69 children with LRTI and hypoxaemia (SpO₂ < 90%) classified as cases and 111 children with the same selection criteria but without hypoxaemia classified as controls (enrolled in two different hospitals: 67 control form the Royal Victoria and 44 from the Medical Research Council, Fajara). Cases and controls were matched by age. Clinical findings were recorded at the time of admission from physical examination and anthropometric measurements. Chest radiographic findings were evaluated by a blinded physician. Using multi‐regression analysis, they derived models to determine the clinical predictors of hypoxaemia. The sensitivity and specificity of each single model was calculated.

The study by Smyth 1998 was performed in Katete, Zambia (1150 MASL). The study included 158 rural children between four weeks and five years with severe or very severe pneumonia according to the WHO classification. Their purpose was to investigate the clinical signs (respiratory rate, chest indrawing, grunting, crepitations/bronchial breathing, cyanosis, failure to drink) that predict hypoxaemia. In a pilot study with 85 healthy infants they established a cut‐off point of normal oxygen saturation at Zambia altitude (SpO₂ > 92%). Data were used to develop a multiple regression equation to predict hypoxaemia stratified by age group. Individual data for the sensitivity and specificity of respiratory rate to confirm the presence of hypoxaemia were reported for nine different cut‐off points (increments of four breaths/min). The SpO₂ measure was taken as the gold standard. Multiple logistic regression analysis was carried out to predict hypoxaemia.

The Usen 1999 study was undertaken in two hospitals in Banjul, Gambia at sea level. The authors analysed data collected as part of the 'haemophilus influenza vaccine for the prevention of infant pneumonia' trial, to study the clinical signs that could predict hypoxaemia. The study included 1072 children aged between 2 and 33 months in the trial cohort who were admitted with pneumonia or any other form of acute LRTI. Any child who had signs of structural heart disease, Down's syndrome or those who had been included in a previous case‐control study of hypoxaemia were excluded. The sensitivity and specificity of symptoms and clinical signs reported by the patients' mothers, as well as multi‐regression models, were used to confirm the presence of hypoxaemia (SpO₂ < 90%). The oximeter readings were taken as the gold standard.

The Gutierrez 2001 study was conducted in Montevideo, Uruguay (43 MASL). A total of 216 hospitalised children between one month and five years with LRTI or with asthma were evaluated to determine the sensitivity, specificity and predictive values of tachypnoea, tachycardia and chest retractions to determine the presence of hypoxaemia associated with LRTI. Children with chronic respiratory distress and neuromuscular diseases were excluded from the study. Hypoxaemia was defined as SpO₂ < 95%. Oxygen saturation measured by oximeter was taken as the gold standard. Results are presented in group of signs or symptoms.

The study by Duke 2002 was conducted in the Eastern Highlands of Papua New Guinea (1600 MASL). Two hundred and fifty‐seven neonates and children (59%) were enrolled in the study with the aim of determining the incidence and severity of hypoxaemia in neonates and children with acute respiratory and non‐respiratory illnesses. To establish normal values of oxygen saturation among well neonates and children they studied 67 neonates and 151 children from 1 to 60 months. Clinical symptoms or signs such as inability to feed, reduced activity, cyanosis, fast respiratory rate, failure to resist examination, grunting and head nodding were assessed as indicators of hypoxaemia (SpO₂ < 86%). Presence of hypoxaemia was determined using the oximeter readings as the gold standard. Logistic regression analysis was used to determine the best independent combination of clinical signs predicting hypoxaemia. Results are presented as odds ratio, sensitivity, specificity, and positive and negative predictive values for each predictive model.

The Lodha 2004 study was conducted in the Indian Institutes of Medical Sciences, New Delhi (239 MASL). One hundred and nine children less than five years of age were evaluated in a cross‐sectional study, with the aim of determining the prevalence of hypoxaemia (SpO₂ < 90%) in children with acute LRTI and identifying the clinical signs associated with the presence of hypoxaemia in children with LRTI. Children with a history of cough and rapid respiration or difficulty in breathing were included. Children with asthma, congenital heart disease, severe anaemia, peripheral circulatory failure, needing ventilatory support and severe dehydration were excluded. Data were obtained from the mother's report about the presence and duration of various respiratory symptoms, and by physical examination of the child to establish the presence of signs such as: appearance, weight, heart rate, respiratory rate, oxygen saturation, cyanosis, chest retraction, grunting, nasal flaring, head nodding, pallor, crepitation or rhonchi and the state of consciousness. Sensitivity, specificity and likelihood ratios were calculated for each symptom or sign and for various combinations of clinical signs as well. The oximeter readings were taken as the gold standard.

The Laman 2005 study was done in Port Moresby, Papua New Guinea (at sea level). The study included 77 children between 1 and 60 months of age with a diagnosis of moderate or severe pneumonia defined according to the WHO classification. Children with underlying pathology such as congenital heart disease, asthma, HIV infection and severe malnourishment (< 60% standard weight for age) were excluded. History and clinical signs were taken at the time of admission. Clinical findings were correlated with different levels of hypoxaemia (< 93%, < 90% and < 85%). Sensitivity, specificity and predicted values of clinical signs were calculated for each level of hypoxaemia established in advanced, using the oximeter readings as the gold standard.

The study by Basnet 2006 was conducted from December 1999 to July 2000 in the Kathmandu valley (1336 MASL). Trial authors assessed the prevalence of hypoxaemia (SpO₂ < 90%) in 264 children, aged from two months to five years, with a diagnosis of pneumonia. Children with heart disease or any other disease were excluded. Data about relevant history of the illness and examination were collected following a structured questionnaire prepared in advanced, before the child received any treatment. Based on the clinical findings the patients were categorised into four groups according to the severity of illness described in the WHO guidelines. They determined the frequency and the increase of hypoxaemia according to the severity of the illness. Sensitivity and specificity of clinical signs were calculated, taking the oximeter readings as the gold standard.

The study by Kuti 2013 was conducted in Gambia at sea level, with the aim of determining factors that predict hypoxaemia at presentation in children with severe pneumonia. They included 420 patients aged from 2 to 59 months with severe pneumonia, 81 of them had hypoxaemia (oxygen saturation < 90%). Children aged 2 to 11 months, with grunting respiration, cyanosis and head nodding and those with cardiomegaly on chest radiograph were at higher risk of hypoxaemia. Patients with wheeze and cough lasting more than two weeks were excluded. All patients enrolled had a chest radiograph at admission and were examined to obtain weight, height to derive nutritional state parameters, axillary temperature, respiratory rate, nasal flaring, presence of pallor, central cyanosis, head nodding, altered sensorium at presentation and abnormal breath sounds on auscultation as well as abnormal heart sounds were recorded. Oxygen saturation was measured using a pulse oximeter and recorded after stabilisation of the reading by a trained nurse. All children were placed on intravenous antibiotics for pneumonia. Grunting respiration and cyanosis were independent predictors of hypoxaemia in childhood pneumonia. They concluded that children that grunt and are centrally cyanosed should be preferentially commenced on oxygen therapy even when there is no facility to confirm hypoxaemia.

The Orimadegun 2013 study was conducted in south western Nigeria, at sea level. The authors investigated the prevalence and predictors of hypoxaemia in ALRI and non‐ALRI according to age and primary diagnoses. The study included 1726 children admitted to a tertiary hospital from which 313 were diagnosed with ALRI. Oxygen saturation was measured shortly after admission. Hypoxaemia was defined as 90% oxygen saturation. Clinical features and the primary admission diagnoses were recorded. Prevalence of hypoxaemia according to age and diagnoses was calculated. Signs and symptoms associated with hypoxaemia were compared between children with ALRI and those with non‐ALRI. Logistic regression was used to determine the association between clinical signs and hypoxaemia adjusting for age.

Case reports assessing adverse events

Two case report studies were found describing severe adverse events related to non‐invasive oxygen delivery methods in infants between three months and five years of age with LRTI (Campos 1994; Frenckner 1990). The characteristics of the studies reporting adverse events are presented in Table 1.

Frenckner 1990 reported a pneumocephalus detected in an eight‐month old girl with severe staphylococcal pneumonia. Supplementary oxygen was delivered through a nasopharyngeal catheter introduced 5 to 7 cm from the nostril. Twenty‐four hours after the catheter insertion, exophthalmos was noticed. The computed tomography (CT) scans showed a pronounced pneumocephalus with 2 cm of subdural air in the frontal region. It was determined that the catheter had perforated the skull bone and had been located intracranial.

Campos 1994 reported a pneumocephalus and right sided severe exophthalmos developed by an 11‐month old boy while he was receiving oxygen by a nasopharyngeal catheter as part of the treatment of bacterial pneumonia and sinusitis. The catheter was inserted in the right nostril and was delivering oxygen at 2 L/min. The adverse event occurred eight days after the catheter insertion. The CT scan revealed air in the orbital cavity and a moderate pneumocephalus in the frontal and right temporal regions.

The effectiveness of oxygen therapy in the treatment of severe lower respiratory tract infections (LRTIs) in children

2. Improvement in respiratory signs achieved during the first 24 hours after oxygen therapy was initiated

The Singhi 2012 study reported on the "cessation of lower chest indrawing and tachypnoea". The results showed that for lower chest indrawing and tachypnoea no significant differences were shown between groups (one study; 58 participants; chest indrawing: standardised mean difference (SMD) 6.64, 95% CI ‐10.77 to 24.06 (Analysis 1.3); tachypnoea: SMD 4.49, 95% CI ‐16.30 to 25.28) (Analysis 1.2). Similar findings were reported for the duration of hypoxaemia in those children who developed this outcome in both groups. In a subgroup analysis comparing those who remained normoxaemic with those who developed hypoxaemia, the authors found similar baseline clinical and laboratory characteristics. However, children who developed hypoxaemia had presented with lower SpO₂ at time of enrolment, and had significantly longer tachypnoea (Figure 2) and longer presence of lower chest indrawing (Figure 3). These findings were similar among children in both interventions groups.

Figure 3

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Forest plot of comparison: 1 Supplemental oxygen versus room air, outcome: 1.3 Duration of chest indrawing.

The effectiveness and safety of non‐invasive oxygen delivery methods

We found four studies assessing the efficacy of non‐invasive delivery methods for the treatment of LRTI in children. Three studies were randomised controlled trials (RCTs) and evaluated the effectiveness of nasal prongs or nasal cannula compared with nasopharyngeal catheter (Muhe 1997; Muhe 1998; Weber 1995). One non‐RCT compared head box, face mask, nasopharyngeal catheter and nasal cannula (Kumar 1997). All reported outcomes considered nasopharyngeal catheters or nasal catheters as the control group, as they are the most widely used methods in low‐income countries.

Comparison 1. Effectiveness of nasal prongs versus nasopharyngeal catheter in the treatment of severe acute LRTIs in children

1. Treatment failure

Three of the included studies assessed the effectiveness of nasal prongs in comparison with nasopharyngeal catheter (Kumar 1997; Muhe 1997; Weber 1995) (Analysis 2.1; Figure 4). These studies reported treatment failure as the number of children that failed to achieve adequate SaO₂ in the hours after each method was administered. The pooled estimate of the effect from the RCTs showed a concerning trend towards no difference in treatment failure between groups (two studies; 239 participants; RR 0.93, 95% CI 0.36 to 2.38; I² statistic = 0%) (Analysis 2.1; Figure 4). Results from the non‐RCT also showed a trend towards to no difference in treatment failure between groups (one study; 160 participants; RR 1.00, 95% CI 0.44 to 2.27) (Analysis 2.1; Figure 4).

Figure 4

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Forest plot of comparison: 2 Nasal prongs versus nasopharyngeal catheter, outcome: 2.1 Treatment failure to achieve adequate oxygenation.

One study compared the effectiveness of nasal prongs versus nasal catheter (Muhe 1998). This study reported treatment failure as the mean number of episodes of oxygen desaturation per child. In the nasal catheter group 36 children presented with oxygen desaturation (mean 2.75; standard deviation (SD) ± 2.18 episodes/child) and in the nasal prongs group 38 children presented with oxygen desaturation (mean 3; SD ± 2.5 episodes/child). This study also showed no difference in the frequency of episodes of desaturation between the groups (t test P value = 0.64). According to the GRADE approach, we considered the quality of the body of evidence for this outcome very low due to important risk of bias and serious imprecision (summary of findings Table for the main comparison).

4. Type and frequency of side effects

Muhe 1997, Muhe 1998 and Weber 1995 reported the presence of nasal obstruction/severe mucus production, nose ulceration or bleeding, fighting or discomfort in the first 24 hours and deaths.

The only adverse effect that showed a significant difference between groups was nasal obstruction due to severe mucus production. It was less frequent in the nasal prongs group (three studies; 338 participants; RR 0.20, 95% CI 0.09 to 0.44; I² statistic = 0%) (Analysis 2.3). According to the GRADE quality assessment, the quality of the evidence for this outcome is low due to risk of bias in trial design and imprecision in the estimates (summary of findings Table for the main comparison).

Nose ulceration or bleeding (Analysis 2.4; Figure 5), fighting or discomfort in the first 24 hours (Analysis 2.5) and deaths (Analysis 2.6; Figure 6) were shown to be less frequent in the nasal prongs group. However, the pooled effect estimates showed a lack of precision, therefore they could not be considered to show significant differences between the groups. We considered the quality of the evidence for these two outcomes low due to risk of bias and imprecision (summary of findings Table for the main comparison).

Figure 5

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Forest plot of comparison: 2 Nasal prongs versus nasopharyngeal catheter, outcome: 2.4 Nose ulceration or bleeding.

Figure 6

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Forest plot of comparison: 2 Nasal prongs versus nasopharyngeal catheter, outcome: 2.6 Death during treatment.

Comparison 2. Effectiveness of face mask versus nasopharyngeal catheter in the treatment of severe acute LRTIs in children

Comparison 3. Effectiveness of head box versus nasopharyngeal catheter in the treatment of severe acute LRTIs in children

1. Clinical criteria that would indicate the need for oxygen therapy or hypoxaemia in children with LRTI

To describe the oxygen saturation values or clinical signs that would indicate the use of oxygen therapy, we included 13 studies conducted with the aim of assessing the accuracy of each sign and symptom present at the time of admission to indicate the presence of hypoxaemia. The included studies showed important sources of clinical heterogeneity, such as population baseline characteristics (type and severity of underlying diseases, age groups etc). Due to this heterogeneity we did not perform a meta‐analysis.

Since most of the included studies assessed similar signs and symptoms as predictors of hypoxaemia, we presented the findings in tables grouped by each sign reported within a consistent definition among studies (Table 2; Table 3; Table 4; Table 5; Table 6; Table 7; Table 8; Table 9; Table 10). As already stated, the definition of hypoxaemia used was different in the included studies and was established, in the majority of cases, by evaluating healthy children from a similar population. Differences in altitude and the definition of hypoxaemia used are also presented in these tables.

2. Sensitivity and specificity of signs and symptoms detecting hypoxaemia

The clinical signs more commonly reported were cyanosis, tachypnoea, nasal flaring, grunting, chest indrawing, crepitations, difficulty in feeding and alteration in mental status. The sensitivity and specificity of these signs varied between studies and age groups. Cyanosis, grunting, difficulty in feeding and alteration of mental status were shown to have better specificity in predicting hypoxaemia and the results were consistent among studies. However, the sensitivity of these signs was variable, especially for the presence of cyanosis, and was not related to the age group or the altitude.

The presence of crepitations at the time of admission was shown to have good sensitivity (min 50, max 93) for determining the presence of hypoxaemia in all age groups, but this sign was not specific in most of the studies (Table 10).

Tachypnoea was shown to have better sensitivity in the prediction of hypoxaemia in children from 2 to 11 months, especially when the cut‐off point used to define tachypnoea was 50 breaths/minute (Table 8). The specificity of this sign is quite different between age groups (2 to 11 months; older than 12 months) and depends on the cut‐off point chosen. This means that tachypnoea alone is not a useful indicator for oxygen therapy.

Study results also showed that the sensitivity and specificity of indrawing are widely variable in all age groups reported (sensitivity: min 32, max 98; specificity: min 7, max 94) (Table 5). For this reason, the use of this sign as the only indicator for oxygen therapy, as the WHO recommends, could lead clinicians to an inappropriate use of this limited resource.

The presence of nasal flaring was the only sign reported that showed consistent characteristics as an indicator for the presence of hypoxaemia in all included studies (Table 4). It was studied in populations of children aged between seven days and five years and was shown to have overall good sensitivity (min 48, max 98) and specificity (min 54, max 98), except in one study conducted in infants from 2 months to 36 months where its specificity was 17.

3. Factors influencing the duration of oxygen therapy with each delivery method

None of the included studies reported on the factors influencing duration of oxygen therapy with each delivery method.

4. Clinical criteria for ending oxygen therapy

None of the included studies reported on clinical criteria for ending oxygen therapy.

5. Clinical criteria for continuing oxygen therapy after discharge

None of the included studies reported on continuing oxygen therapy after discharge.

6. Costs associated with each method

None of the included studies reported on costs associated with each method.