Solución salina hipertónica nebulizada para la bronquiolitis aguda en lactantes
Referencias
Referencias de los estudios incluidos en esta revisión
Referencias de los estudios excluidos de esta revisión
Referencias de los estudios en espera de evaluación
Referencias adicionales
Referencias de otras versiones publicadas de esta revisión
Characteristics of studies
Characteristics of included studies [ordered by study ID]
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: paediatric emergency facility in Qatar Inclusion criteria: infants aged ≤ 18 months, with a prodromal history of viral upper respiratory tract infection, followed by wheezing or crackles, or both on auscultation and Wang clinical severity score ≥ 4 Exclusion criteria: born at ≤ 34 weeks’ gestation, previous history of wheezing, steroid use within 48 h of presentation, obtundation and progressive respiratory failure requiring ICU admission, history of apnoea within 24 hours before presentation, SaO₂ ≤ 85% on room air at the time of recruitment, history of a diagnosis of chronic lung disease, congenital heart disease, or immunodeficiency | |
| Interventions | Intervention groups: Control group: nebulised 0.9% saline (5 mL) plus 1.5 mL of epinephrine Treatment was given every 4 hours, until the infant was ready for discharge. Nebulised medications were delivered through a tight‐fitting face mask by pressurised oxygen with the flow meter set at 10 L/min. | |
| Outcomes |
| |
| Notes | Virological identification not available. Supported by Hamad Medical Corporation, which employs all but 1 author who previously worked at Hamad. The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐based randomisation program |
| Allocation concealment (selection bias) | Low risk | Sequentially numbered and sealed envelopes |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawals after randomisation reported. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: 24 paediatric emergency departments in France Inclusion criteria: infants aged 6 weeks to 12 months with first episode of moderate to severe bronchiolitis defined as viral upper respiratory tract infection plus wheezing or crackles, or both on chest auscultation with respiratory distress Exclusion criteria: premature birth (birth before 37 weeks of gestation), immunologic, cardiac, or chronic pulmonary disease, bone malformation of the chest, previous use of nebulised hypertonic saline, inability to communicate with the family (a language barrier or lack of telephone for contact), need of admission to a paediatric ICU | |
| Interventions | Intervention group: nebulised 3% saline (4 mL) Control group: nebulised 0.9% saline (4 mL) Study medication was given at 0 and 30 min using a jet nebuliser through a firmly applied face mask with an oxygen flow rate of 6 L/min. | |
| Outcomes |
| |
| Notes | RSV‐positive: 84.5% in hypertonic saline group; 88.2% in control group Supported by grant P110143/IDRCB2012‐A00228‐35 from the French Hospital Program for Clinical Research/French Ministry of Health. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated random allocation sequence using a 1:1 ratio and permutation blocks with a block size of 4, stratified according to centre |
| Allocation concealment (selection bias) | Low risk | The investigational pharmacy prepared the study drugs in sequentially numbered and visually identical packets. Randomisation codes were kept secure until data entry was complete. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blinded |
| Incomplete outcome data (attrition bias) | Low risk | Hospitalisation data were not available for 5 infants (2 in hypertonic saline group and 3 in normal saline group). |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: emergency department of a teaching hospital in Turkey Inclusion criteria: infants with diagnosis of bronchiolitis requiring a history of upper respiratory infection and the presence of bilateral wheezing or crackles, or both on chest auscultation, plus clinical severity score between 1 and 9 Exclusion criteria: prematurity, any underlying disease (e.g. cystic fibrosis, bronchopulmonary dysplasia, and cardiac or renal disease), prior history of wheezing, atopic dermatitis, allergic rhinitis or asthma, SaO₂ < 85% on room air, clinical severity score > 9, obtunded consciousness, progressive respiratory failure requiring mechanical ventilation, previous treatment with bronchodilators, and any steroid therapy within 2 weeks | |
| Interventions | Intervention groups: Control groups: The study drug was administered at 0 and 30 min by Medic‐Aid Sidestream nebuliser (Medic‐Aid Ltd, West Sussex, UK) using a face mask with continuous flow of 100% oxygen at 6 L/min. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐based randomisation program |
| Allocation concealment (selection bias) | Unclear risk | Study medications were identical in appearance and odour, but no other details were provided regarding allocation concealment. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawals after randomisation reported. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: double‐blind, randomised controlled trial | |
| Participants | Setting: inpatient ward of a university tertiary hospital in Malaysia Inclusion criteria: previously healthy infants younger than 18 months, having first hospitalisation with mild to moderate acute bronchiolitis, defined as strong clinical suspicion of viral lower respiratory tract infection associated with airways obstruction as manifested by hyperinflation, tachypnoea and subcostal recession with widespread crepitations, prolonged expiratory phase and rhonchi on auscultation Exclusion criteria: other lower airway infection such as pneumonia, chronic respiratory disorders, i.e. chronic lung disease, congenital lung or airway malformation, bronchial asthma, previous hospitalisation for wheezing episode, and other underlying chronic illnesses such as gastro‐oesophageal reflux and congenital heart disease | |
| Interventions | Intervention group: nebulised 3% saline (3.5 mL) plus salbutamol (2.5 mg, 0.5 mL) Control group: nebulised 0.9% normal saline (3.5 mL) plus salbutamol (2.5 mg, 0.5 mL) The study solutions were given every 6 hours, via a nebuliser with mask and oxygen (5 L/min), until clinical severity score ≤ 4. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funded by a Short Term grant (304/PPSP/61313039) from the Universiti Sains Malaysia. Declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐based randomisation program |
| Allocation concealment (selection bias) | Low risk | Sealed and opaque envelopes containing the choice of therapy, which were numbered accordingly |
| Blinding (performance bias and detection bias) | Low risk | Parents, care providers, investigators, and outcome assessor were blinded. Preparation of the nebulised solutions was done by an independent pharmacist. The solutions were indistinguishable by colour, appearance, or smell. |
| Incomplete outcome data (attrition bias) | Low risk | 1 withdrawal after randomisation in the control group |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind controlled trial | |
| Participants | Setting: inpatient ward of a tertiary teaching hospital, India Inclusion criteria: previously healthy infants, aged 2 to 18 months, hospitalised with first episode of respiratory tract infection with wheeze, starting as a viral upper respiratory infection (coryza, cough, or fever), and with a clinical score between 4 and 8 Exclusion criteria: previous episode of wheezing, chronic cardiopulmonary disease or immunodeficiency; critical illness at presentation requiring admission to intensive care; the use of nebulised hypertonic saline within the previous 12 hours; or premature birth (gestational age 34 weeks) | |
| Interventions | Intervention group: nebulised 3% saline solution (4 mL) Control group: nebulised 0.9% saline solution (4 mL) The study solutions were given every 2 hours for 3 doses, followed by every 4 hours for 6 doses, then by every 6 hours until discharge. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding sources not provided. The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐based randomisation program |
| Allocation concealment (selection bias) | Unclear risk | No details provided. |
| Blinding (performance bias and detection bias) | Low risk | Study solutions were prepared to be identical appearance. Codes of solutions were blinded to all participants, care providers, and investigators. |
| Incomplete outcome data (attrition bias) | Low risk | 5 (2.6%) withdrawals after randomisation, 1 in the hypertonic saline group and 4 in the normal saline group. All infants included in the final intention‐to‐treat analysis. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: multicentre, parallel‐group, open, randomised controlled trial | |
| Participants | Setting: assessment units and paediatric wards of 10 participating centres in England and Wales Inclusion criteria: infants < 12 months with diagnosis of bronchiolitis defined as an apparent viral respiratory tract infection associated with airways obstruction manifest by hyperinflation, tachypnoea and subcostal recession with widespread crepitations on auscultation, needing supplementary oxygen for SaO₂ of < 92% in air Exclusion criteria: history of wheezy bronchitis or asthma, gastro‐oesophageal reflux, previous lower respiratory tract infections, risk factors for severe disease, carers lacking fluent English in the absence of translator service, and requiring admission to high‐dependency or intensive care units at presentation | |
| Interventions | Intervention group: 4 mL 3% saline + standard care Control group: standard care Hypertonic saline given every 6 h, administered via PARI Sprint nebuliser with appropriate face mask, until primary outcome achieved. | |
| Outcomes |
| |
| Notes | RSV‐positive: 58.5% in hypertonic saline group; 64.4% in control group Funded by the National Institute for Health Research Health Technology Assessment (HTA) Programme (project number 09/91/22). All but 1 author declare no conflicts of interest. PSMN received personal fees/honoraria from Paul Alios Biopharma and Janssen Pharmaceuticals for consultancy and advisory board membership. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation in blocks of size 2, 4, and 6, stratified by hospital |
| Allocation concealment (selection bias) | Low risk | Centralised web‐based randomisation system |
| Blinding (performance bias and detection bias) | High risk | Open study |
| Incomplete outcome data (attrition bias) | Unclear risk | 27 (8.5%) withdrawals after randomisation (17 hypertonic saline group, 10 control group). Reasons for withdrawals not reported. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: paediatric ward of a general urban hospital in Portugal Inclusion criteria: infants aged < 12 months with acute bronchiolitis, defined as an apparent viral respiratory tract infection manifested by nasal discharge and wheezy cough, with presence of fine inspiratory crackles and/or high‐pitched expiratory wheeze, even apnoea Exclusion criteria: previous episodes of wheezing, personal history of prematurity (gestational age < 34 weeks), physician diagnosis of eczema, food allergy, or chronic (cardiac, respiratory, immunological, neurological, or metabolic) disease, and high severity criteria (coma, respiratory rate > 80 breaths/minute, SaO₂ < 88% on room air or need for assisted ventilation) | |
| Interventions | Intervention group: nebulised 3% saline (3 mL) plus 0.25 mL (1.25 mg) salbutamol Control group: nebulised 0.9% saline (3 mL) plus 0.25 mL (1.25 mg) salbutamol Treatment was given every 6 h until discharge. All inhaled therapies were delivered through a tight‐fitting face mask from an oxygen‐driven nebuliser (Cirrus 2 Nebuliser, Wokingham, Berkshire, UK), connected to a source of pressurised oxygen from the wall, set to a flow rate of 6 L/min. | |
| Outcomes |
| |
| Notes | RSV‐positive: 87.9% in hypertonic saline group; 82.9% in normal saline group Funding source: none The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation |
| Allocation concealment (selection bias) | Low risk | Both solutions were similar in appearance and smell, stored in identical syringes, and labelled only by a code number. Randomisation list was concealed by the pharmacy. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 10 (12.8%) withdrawals after randomisation (5 hypertonic saline group, 5 control group) because of clinical deterioration with need for ICU |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: urban paediatric emergency department in the USA Inclusion criteria: children aged 2 months up to 24 months presenting to the emergency department with acute bronchiolitis, defined as a first episode of wheezing associated with signs and symptoms of respiratory distress and upper respiratory infection, with RDAI score of 4 to 15 (moderate to severe) Exclusion criteria: infants with a history of wheezing or asthma, bronchodilator therapy prior to the current illness, chronic lung or heart disease, critical illness, inability to receive nebulised medications, and infants with non–English‐speaking guardians | |
| Interventions | Intervention group: nebulised 3% saline (4 mL) Control group: nebulised 0.9% saline (4 mL) Treatment delivered using a jet nebuliser with an oxygen flow rate of 8 L/min. Study medication was given within 90 minutes after albuterol administration. | |
| Outcomes |
| |
| Notes | Virological identification not available. Supported by a Young Investigator Award from the Academic Pediatric Association. The Academic Pediatric Association had no role in the design and conduct of the study; collection, management, analysis, and The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated random permuted block randomisation |
| Allocation concealment (selection bias) | Low risk | The investigational pharmacy prepared the study medications, which were stored in sequentially numbered envelopes with blinded syringes labelled only with the study number. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawals reported. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: emergency department of a children's hospital in Canada Inclusion criteria: infants aged 6 weeks to 12 months presenting with a first episode of wheezing and clinical symptoms of a viral respiratory infection, plus an initial SaO₂ of 85% or more but 96% or less, and RDAI score ≥ 4 Exclusion criteria: pre‐existing cardiac or pulmonary disease, previous diagnosis of asthma by a physician, any previous use of bronchodilators (except for treatment of the current illness), severe disease requiring resuscitation room care, inability to take medication using a nebuliser, inability to obtain informed consent secondary to a language barrier, or no phone access for follow‐up | |
| Interventions | Intervention group: nebulised 3% saline (2.5 mL) plus 0.5 mL 2.25% racaemic epinephrine Control group: nebulised 0.9% saline (2.5 mL) plus 0.5 mL 2.25% racaemic epinephrine Both groups received inhalation solutions at 0 minutes. Each treatment was given by nebuliser with continuous flow of oxygen at 6 L/min. 2 doses of the study drug were available for each infant such that, if the physician felt that a second dose of racaemic epinephrine was needed during the 120‐minute study period, the infant received the same drug combination again. | |
| Outcomes |
| |
| Notes | RSV‐positive: 82.6% in hypertonic saline group; 81.8% in normal saline group Supported by the Department of Pediatrics, University of Alberta; and the Alberta Research Centre for Child Health Evidence. Personnel for data collection were funded by the Department of Pediatrics, University of Alberta. Statistical analysis and interpretation of data were graciously provided by the Alberta Research Centre for Child Health Evidence. The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Website randomisation scheme |
| Allocation concealment (selection bias) | Low risk | The solutions prepared by the hospital pharmacy were similar in appearance and smell, stored in identical syringes, labelled only by a code number, and placed in the research cupboard within the emergency department. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 2 (4.1%) withdrawals (1 hypertonic saline group; 1 normal saline group) |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised clinical trial | |
| Participants | Setting: inpatient ward of a hospital in India Inclusion criteria: children aged 3 months to 2 years admitted with features of acute bronchiolitis Exclusion criteria: bacterial or aspiration pneumonia, previous wheezing episodes, oxygen saturation < 92% in room air, cyanosis, obtunded consciousness, progressive respiratory failure requiring mechanical ventilation, foreign body inhalation, cardiac disease, congenital malformations, and parents refusing consent | |
| Interventions | Intervention group: nebulised 3% saline (3 mL) plus salbutamol (? mL) Control group: nebulised 0.9% saline (3 mL) plus salbutamol (? mL) The medication was given every 6 hours until discharge, via an Apex Eco‑Plus nebuliser (Apex Medical Corp, France). | |
| Outcomes |
| |
| Notes | Virological identification not available. Bronchiolitis diagnosis criteria not provided. Financial support and sponsorship: nil The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Standard randomisation table |
| Allocation concealment (selection bias) | Unclear risk | No details provided. |
| Blinding (performance bias and detection bias) | Unclear risk | No details provided. |
| Incomplete outcome data (attrition bias) | Unclear risk | No report of withdrawals |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: quasi‐randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: paediatric emergency department of a training and research hospital in Turkey Inclusion criteria: age < 2 years, a history of preceding viral upper respiratory infection followed by wheezing and crackles on auscultation, and a clinical severity score of 4 to 8 on admission Exclusion criteria: infants with clinical severity score < 4 or > 8, SaO₂ < 85% on room air, chronic cardiac illness, premature birth, birthweight < 2500 g, history of recurrent wheezing episodes, proven immune deficiency, severe neurological disease, age < 1 month or > 2 years, consolidation or atelectasis on a chest roentgenogram | |
| Interventions | Intervention groups: Control groups: Treatment was given every 20 min until 3 doses had been administered (0, 20, and 40 min). All inhaled therapies were delivered via a compressor nebuliser through a face mask with continued flow of oxygen at 4 to 5 L/min (Mini Compressor Nebulizer, CN‐02WD, Ace‐Tec Co, Ltd, Guangdong, China). | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | High risk | Infants were assigned to 1 of 4 groups according to the consecutive order of their admission to the short‐stay unit. |
| Allocation concealment (selection bias) | High risk | As stated above |
| Blinding (performance bias and detection bias) | Unclear risk | The trial was stated as double‐blind, but no details were provided. |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawals reported. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: emergency department of an urban tertiary care centre in the USA Inclusion criteria: infants aged 6 weeks to 18 months presenting to the emergency department with acute bronchiolitis, defined as viral respiratory illness and first episode of wheeze, and a modified Wang clinical severity score of ≥ 4 Exclusion criteria: previous history of wheezing, any use of bronchodilators within 2 hours of presentation, gestational age ≤ 34 weeks, history of congenital heart disease or chronic pulmonary or chronic renal disease, SaO₂ ≤ 85% at the time of recruitment, severe disease requiring ICU admission, or inability to obtain informed consent | |
| Interventions | Intervention group: nebulised 7% saline (3 mL) plus 2.25% racaemic epinephrine (0.5 mL) Control group: nebulised 0.9% saline (3 mL) plus 2.25% racaemic epinephrine (0.5 mL) The medication was given via a nebuliser driven by oxygen flow at 6 L/min after initial screening and assessment. If admitted, the infant continued to receive the same designated medication every 6 h until discharge or 24 h after admission. | |
| Outcomes |
| |
| Notes | RSV‐positive: 68% in hypertonic saline group; 50% in control group Funding: no external funding The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomisation in blocks of 10, but it is unclear how to choose blocks at random to create the allocation sequence |
| Allocation concealment (selection bias) | Low risk | Sequentially numbered, concealed envelopes containing either 7% or 0.9% saline solution |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawals reported. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised multicentre clinical trial | |
| Participants | Setting: emergency department of 2 hospitals in Switzerland Inclusion criteria: children aged 6 weeks up to 24 months with a first episode of acute bronchiolitis, defined as symptoms of upper respiratory tract infection in addition to tachypnoea, wheezing, and widespread crackles at auscultation, and with a Wang score of 5 to 12 (moderate to severe) on arrival Exclusion criteria: mild bronchiolitis (Wang score < 5), previous episodes of wheezing, cardiac or chronic respiratory disease, immunocompromised, gestational age < 34 weeks, requiring immediate admission to ICU, RSV immunoglobulin therapy, corticotherapy in the preceding 2 weeks, bronchodilators within 24 hours prior to presentation | |
| Interventions | Intervention group: nebulised 3% saline (4 mL) plus standard care Control group: standard care only The medication was given every 6 hours until discharge, via Pari LC sprint nebulisers with an oxygen flow at 6 L/min. Nebulised 4 mg epinephrine could be administered up to 3 times within the hour if child showed signs of respiratory failure (either persistent major respiratory distress, signs of exhaustion with a partial pressure of carbon dioxide above > 50 mmHg on the capillary blood gas) | |
| Outcomes |
| |
| Notes | Virological identification not available. Bronchiolitis diagnosis criteria not provided. Funding: none The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation program in blocks of 10 |
| Allocation concealment (selection bias) | Unclear risk | No details provided. |
| Blinding (performance bias and detection bias) | Unclear risk | No details provided. |
| Incomplete outcome data (attrition bias) | Unclear risk | No report of withdrawals |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: emergency and outpatient departments of a children's hospital in Nepal Inclusion criteria: infants aged 6 weeks to 2 years with acute bronchiolitis defined as the first episode of acute wheezing, starting as a viral upper respiratory infection (coryza, cough, or fever), with Wang clinical severity score between 1 and 9 Exclusion criteria: any underlying disease (e.g. cystic fibrosis, bronchopulmonary dysplasia, and cardiac or renal disease), prior history of wheezing, diagnosed case of asthma, SaO₂ < 85% on room air, clinical severity score > 9, progressive respiratory distress requiring mechanical ventilation, previous treatment with bronchodilators within last 4 h, and any steroid therapy within 48 h | |
| Interventions | Intervention group: nebulised 3% saline (4 mL) plus L‐epinephrine (1.5 mg) Control group: nebulised 0.9% saline (4 mL) plus L‐epinephrine (1.5 mg) The study drug was administered at 0 and 30 min by a jet nebuliser using a face mask. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding sources not provided. The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated block randomisation (in blocks of 10) |
| Allocation concealment (selection bias) | Low risk | Study solutions were labelled with the codes and wrapped in an envelope bearing the respective codes. Study solutions were identical in appearance and odour. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 1 (1%) withdrawal after randomisation in hypertonic saline group |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: inpatient wards of 3 regional tertiary care hospitals, 1 in United Arab Emirates and 2 in Canada Inclusion criteria: infants with diagnosis of moderately severe bronchiolitis requiring a history of a preceding viral upper respiratory infection, the presence of wheezing or crackles on chest auscultation, plus either an SaO₂ < 94% in room air or RDAI score ≥ 4 Exclusion criteria: previous episode of wheezing, chronic cardiopulmonary disease or immunodeficiency, critical illness at presentation requiring admission to intensive care, the use of nebulised hypertonic saline within the previous 12 h, or premature birth (gestational age ≤ 34 weeks) | |
| Interventions | Intervention group: nebulised 3% saline (4 mL) Control group: nebulised 0.9% saline (4 mL) Treatment was given every 2 h for 3 doses, followed by every 4 h for 5 doses, followed by every 6 h until discharge. All inhaled therapies were delivered to a settled infant from a standard oxygen‐driven hospital nebuliser through a tight‐fitting face mask or head box, whichever the infant tolerated better. | |
| Outcomes |
| |
| Notes | RSV‐positive: 62% in hypertonic saline group; 75% in normal saline group Supported by the Queen Alexandra Foundation for Children, British Columbia, Canada; Vancouver Island Health Authority, Youth and Maternal Programme, British Columbia, Canada; and an Ontario Thoracic Society block term grant. Declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐based randomisation program |
| Allocation concealment (selection bias) | Low risk | Study solutions were prepared by a research pharmacist and were identical in appearance and odour. The identity of the study solutions was blinded to all participants, care providers, and investigators. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 5 (5.2%) withdrawals after randomisation (2 hypertonic saline group; 3 normal saline group); intention‐to‐treat analysis used |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: inpatient wards of a children's hospital in Turkey Inclusion criteria: infants aged 1 to 24 months with clinical diagnosis of bronchiolitis, defined as the first wheezing episode followed by a viral upper respiratory infection, with crackles on auscultation, and Wang clinical severity score ≥ 4 Exclusion criteria: infants with clinical severity score < 4, SaO₂ < 80% in room air, chronic cardiopulmonary or neurological disease, premature birth, birthweight < 2500 g, history of recurrent wheezing episodes, proven immune deficiency, age < 1 month or > 2 years, proven or suspected acute bacterial infection, previous treatment with bronchodilators or corticosteroids, the presence of symptoms > 7 days, consolidation or atelectasis on a chest roentgenogram | |
| Interventions | Intervention groups: Control group: nebulised 0.9% saline (2.5 mL) plus salbutamol (0.15 mg/kg) 2 doses were given at 30‐minute interval, followed by every 6 h until discharge. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding: none The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated stratified randomisation |
| Allocation concealment (selection bias) | Unclear risk | No details provided. |
| Blinding (performance bias and detection bias) | Unclear risk | The trial was stated as double‐blind, but no details were provided. |
| Incomplete outcome data (attrition bias) | Low risk | 2 (1.9%) withdrawals after randomisation in 7% saline group |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, parallel‐group, controlled trial | |
| Participants | Setting: outpatient department of a children's hospital in China Inclusion criteria: infants aged 2 months to 18 months with clinical diagnosis of acute bronchiolitis and Wang clinical severity score ≥ 4 Exclusion criteria: severe bronchiolitis (respiratory rate > 80 breaths per minute, SaO₂ < 85% on room air or need for mechanical ventilation), immunological deficiency diseases, cardiac diseases, neurological or metabolic diseases, chronic respiratory diseases, prematurity, and previous history of wheezing | |
| Interventions | Intervention groups: Control group: nebulised 0.9% saline (3 mL) The study drug was administered by a jet nebuliser, twice daily for 3 days. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random sequence generated using a random number table |
| Allocation concealment (selection bias) | Unclear risk | No details provided. |
| Blinding (performance bias and detection bias) | Unclear risk | No details provided. |
| Incomplete outcome data (attrition bias) | Low risk | 5 (3.8%) withdrawals after randomisation (1 in 5% saline group, 2 in 3% saline group, 2 in normal saline group) |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: inpatient wards of a teaching hospital for children in China Inclusion criteria: infants with a diagnosis of mild to moderately severe bronchiolitis Exclusion criteria: age > 24 months, previous episode of wheezing, chronic cardiac and pulmonary disease, immunodeficiency, accompanying respiratory failure, requiring mechanical ventilation, inhaling the nebulised 3% saline solution and salbutamol 12 h before treatment, and premature infants born at less than 34 weeks gestation | |
| Interventions | Intervention group: nebulised 3% saline (4 mL) plus 2.5 mg salbutamol Control group: nebulised 0.9% saline (4 mL) plus 2.5 mg salbutamol Infants in each group received 3 treatments every day, delivered at intervals of 8 h until discharge using air‐compressed nebulisers. | |
| Outcomes |
| |
| Notes | RSV‐positive: 70% in hypertonic saline group; 69.7% in normal saline group Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details were reported. |
| Allocation concealment (selection bias) | Low risk | No detectable difference in colour, smell, or other physical properties between the therapeutic packages containing 0.9% saline solution or 3% saline solution. The codes of the therapeutic packages were not available to the investigators, nurses, or parents. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawals reported. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: inpatient ward of a teaching hospital for children in China Inclusion criteria: infants aged < 24 months with a first episode of wheezing, hospitalised for treatment of moderate to severe bronchiolitis Exclusion criteria: age > 24 months, previous episode of wheezing, chronic cardiac and pulmonary disease, immunodeficiency, accompanying respiratory failure, requiring mechanical ventilation, inhaling the nebulised 3% saline solution 12 h before treatment, and prematurity with birth at < 34 weeks of gestation | |
| Interventions | Intervention group: nebulised 3% saline (4 mL) Control group: nebulised 0.9% saline (4 mL) Treatment was given every 2 h for 3 doses, followed by every 4 h for 5 doses, followed by every 6 h until discharge. All inhaled treatments were delivered to infants from standard air‐compressed nebulisers (PARI Corporation, Stanford, Germany). | |
| Outcomes |
| |
| Notes | RSV‐positive: 73.7% in hypertonic saline group; 72.7% in normal saline group Funding sources not provided. The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐based randomisation program |
| Allocation concealment (selection bias) | Low risk | Sequentially numbered, sealed, opaque envelopes |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 14 (11.1%, 7 infants from each group) discharged within 12 hours after enrolment and data were not collected. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: inpatient ward of a teaching hospital in India Inclusion criteria: children aged < 2 years, hospitalised with acute bronchiolitis defined as the first episode of lower respiratory tract infection with wheeze and having a moderate respiratory distress with clinical severity score between 4 and 8 Exclusion criteria: children with pre‐existing cardiac disease, previous wheezing episodes, severe disease (clinical severity score > 8) requiring mechanical ventilation (SaO₂ < 85% on room air, cyanosis, obtunded consciousness, and/or progressive respiratory failure) | |
| Interventions | Intervention group: nebulised 3% saline (3 mL) plus salbutamol (0.15 mg/kg) Control group: nebulised 0.9% saline (3 mL) plus salbutamol (0.15 mg/kg) The medication was given via a nebuliser driven by oxygen flow at 5 to 6 L/min, every 6 h until the infant was ready for discharge. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation |
| Allocation concealment (selection bias) | Unclear risk | No details provided. |
| Blinding (performance bias and detection bias) | Unclear risk | The trial was stated as double‐blind, but no details were provided. |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawals reported. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: paediatric inpatient ward, Edith Wolfson Medical Center, Israel Inclusion criteria: infants with clinical presentation of viral bronchiolitis with temperature > 38 °C that led to hospitalisation Exclusion criteria: cardiac disease, chronic respiratory disease, previous wheezing episode, age > 12 months, SaO₂ < 85% in room air, changes in consciousness and/or progressive respiratory failure requiring mechanical ventilation | |
| Interventions | Intervention group: nebulised 3% saline solution (4 mL) plus 1.5 mg epinephrine Control group: nebulised 0.9% saline solution (4 mL) plus 1.5 mg epinephrine Treatment was given 3 times/day at intervals of 8 h, until the infant was ready for discharge. All inhaled treatments were delivered using a nebuliser (Aeromist Nebulizer Set 61400; B&F Medical by Allied; Toledo, OH) connected to a source of pressurised oxygen at a flow rate of 5 L/min. | |
| Outcomes |
| |
| Notes | RSV‐positive: 85% in hypertonic saline group; 88% in normal saline group Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details provided. |
| Allocation concealment (selection bias) | Low risk | Study solutions were similar in colour, smell, and other physical properties. The code of the therapeutic package (hypertonic saline versus normal saline solution) was deposited with the statistician. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 1 (1.8%) withdrawal after randomisation |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: division of paediatrics of a general hospital in Italy Inclusion criteria: children aged under 2 years with a diagnosis of bronchiolitis, defined as the first episode of wheezing and clinical symptoms of a viral respiratory infection and SaO₂ < 94% in room air and significant respiratory distress Exclusion criteria: pre‐existing cardiac or pulmonary diseases, premature birth < 36 weeks of gestational age, previous diagnosis of asthma, initial SaO₂ ≤ 85% or respiratory distress severe enough to require resuscitation | |
| Interventions | Intervention group: nebulised 3.0% hypertonic saline (volume not reported) plus 1.5 mg epinephrine Control group: nebulised 0.9% saline (volume not reported) plus 1.5 mg epinephrine Study solutions were given at intervals of 6 h until discharge. Each treatment was delivered by a nebuliser with continuous flow of oxygen at 6 L/min through a tight‐fitting face mask. | |
| Outcomes |
| |
| Notes | RSV‐positive: 80.7% in hypertonic saline group; 83.3% in normal saline group Funding sources not provided. The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐based randomisation program |
| Allocation concealment (selection bias) | Unclear risk | Study solutions were prepared by the local hospital pharmacy, but the method of allocation concealment was not described. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 3 withdrawals (1 hypertonic saline group; 2 normal saline group) |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: open‐label, multicentre, randomised controlled trial | |
| Participants | Setting: 2 tertiary children's hospitals and 3 general hospitals in Tokyo, Japan Inclusion criteria: hospitalised infants less than 12 months of age with acute moderate bronchiolitis due to RSV Exclusion criteria: pCO₂ > 60 mmHg, saturation < 95% on oxygen administration, episodes of apnoea, previous episodes of wheezing, cerebral palsy, congenital heart disease, lung disease, muscular disorder, malformation syndrome, immune deficiency disorder, a history of preterm birth defined as a gestational age of less than 36 weeks, and progressive respiratory failure requiring mechanical ventilation or previous administration of palivizumab | |
| Interventions | Intervention group: nebulised 3% saline (2 mL) plus 0.5% salbutamol (0.1 mL) Control group: nebulised 0.9% saline (2 mL) plus 0.5% salbutamol (0.1 mL) All nebulisation therapies were delivered via standard oxygen‐driven hospital nebulisers, 4 times daily, until discharge criteria were fulfilled. | |
| Outcomes |
| |
| Notes | RSV identification was an inclusion criterion. Funding: none The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Central randomisation system |
| Allocation concealment (selection bias) | High risk | Dynamic (minimisation) allocation was used, but participants and treating physicians were not masked to assignment. |
| Blinding (performance bias and detection bias) | High risk | Only biostatisticians were blinded to the allocation during the trial and analysis. |
| Incomplete outcome data (attrition bias) | Low risk | No report of withdrawals |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, open‐label, parallel‐group, controlled trial | |
| Participants | Setting: inpatient ward of a children’s hospital in Buenos Aires, Argentina Inclusion criteria: infants aged 1 to 24 months, hospitalised for first episode of bronchiolitis, with severity score ≥ 5 and oxygen saturation ≥ 97% Exclusion criteria: chronic respiratory or cardiovascular disease, respiratory failure | |
| Interventions | Intervention group: nebulised 3.0% hypertonic saline (3 mL) plus albuterol (0.25 mg/kg/day) Control group: nebulised 0.9% saline (3 mL) plus albuterol (0.25 mg/kg/day) Study solutions were given 4 times a day for 5 days. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | The trial was stated as randomised, but no details were provided. |
| Allocation concealment (selection bias) | Unclear risk | No details provided. |
| Blinding (performance bias and detection bias) | High risk | Open‐label |
| Incomplete outcome data (attrition bias) | High risk | 18 (18%) withdrawals (13 hypertonic saline group, 5 normal saline group); unbalanced attrition between treatment groups |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: inpatient ward of a teaching hospital in Nepal Inclusion criteria: children aged over 6 weeks up to 24 months, hospitalised with acute bronchiolitis, defined as the first episode of wheezing associated with tachypnoea, increased respiratory effort, and an upper respiratory tract infection Exclusion criteria: previous episode of wheezing, chronic cardiac and pulmonary disease, immunodeficiency, accompanying respiratory failure, requiring mechanical ventilation, inhaling the nebulised 3% saline solution and salbutamol 12 h before treatment, premature infants born at less than 34 weeks' gestation, SaO₂ < 85% on room air | |
| Interventions | Intervention group: nebulised 3% saline (4 mL) Control group: nebulised 0.9% saline (4 mL) Treatment was given every 8 h until discharge. | |
| Outcomes |
| |
| Notes | Virological identification not available. Supported by University Grant Commission (UGC). Declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation |
| Allocation concealment (selection bias) | Low risk | The random numbers were kept in a sealed envelope. The solutions were similar in appearance and smell and were kept in 2 identical containers, labelled only by a code number. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | High risk | 13 (18%) withdrawals after randomisation (8 hypertonic saline group; 5 normal saline group). Different reasons for withdrawals between study groups |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, non‐blind, parallel‐group, controlled trial | |
| Participants | Setting: paediatric department of a government multispeciality hospital in India Inclusion criteria: infants aged 2 months to 12 months, admitted with clinical diagnosis of acute bronchiolitis, defined as the first attack of wheezing after a short history of cough with or without fever of less than 7 days duration Exclusion criteria: recurrent episodes of wheezing, 1 or more episodes of respiratory distress in past, family history of asthma, atopy, congenital heart disease, history of prematurity or mechanical ventilation in newborn period, very sick patients with shock, seizures, heart rate > 180/min, respiratory rate > 100/min and adjudged to be in incipient respiratory failure, severe malnutrition, consolidation lung on chest X‐ray | |
| Interventions | Intervention group: nebulised 3% saline (4 mL) plus 1:1000 adrenaline (1 mL) Control group: nebulised 0.9% saline (4 mL) plus 1:1000 adrenaline (1 mL) The medication was given 3 times with an interval of 1 hour, via a nebuliser driven by oxygen flow at 6 to 8 L/min. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding: none The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation |
| Allocation concealment (selection bias) | Low risk | Group allocation was concealed in an opaque envelope. |
| Blinding (performance bias and detection bias) | High risk | Non‐blind |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawals reported. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: inpatient ward of a general hospital in Poland Inclusion criteria: children aged 0 to 18 months, hospitalised with acute bronchiolitis defined as prolonged expiration, wheezes, and crepitations, with a history of a preceding viral upper respiratory infection, and with SaO₂ ≤ 95% or Wang score ≥ 5 Exclusion criteria: preterm babies < 34 weeks, chronic cardiac or respiratory disease, immunological deficiencies, 2 or more episodes of bronchial obstruction, treatment with systemic glucocorticosteroids, received a hypertonic saline nebulisation in 24 hours prior to admission, or with SaO₂ < 85% | |
| Interventions | Intervention group: nebulised 3% saline (3 mL) plus salbutamol (0.15 mg/kg, max 1.5 mg) Control group: nebulised 0.9% saline (3 mL) plus salbutamol (0.15 mg/kg, max 1.5 mg) The medication was given 6 times daily until discharge, via a nebuliser driven by oxygen flow at 6 to 8 L/min. | |
| Outcomes |
| |
| Notes | RSV‐positive: 51% in hypertonic saline group; 56% in normal saline group Funding: none The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation |
| Allocation concealment (selection bias) | Unclear risk | No details provided. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 4 (5.1%) withdrawals (2 infants from each group) |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: Pediatric and Adolescent Ambulatory Community Clinic of General Health Services of Petach‐Tikva, Israel Inclusion criteria: infants with clinical presentation of mild to moderate viral bronchiolitis Exclusion criteria: cardiac disease, chronic respiratory disease, previous wheezing episode, age ≥ 24 months, SaO₂ < 96% on room air, and need for hospitalisation | |
| Interventions | Intervention group: nebulised 3% saline solution (2 mL) plus 5 mg (0.5 mL) terbutaline Control group: nebulised 0.9% saline solution (2 mL) plus 5 mg (0.5 mL) terbutaline Treatment was given 3 times/day at intervals of 8 h for 5 days. | |
| Outcomes |
| |
| Notes | RSV‐positive: 82% in hypertonic saline group; 78% in normal saline group Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation in blocks of 4, using an online randomiser |
| Allocation concealment (selection bias) | Low risk | Study solutions were similar in colour, smell, and other physical properties. The code of the therapeutic package (hypertonic saline versus normal saline solution) was deposited with the statistician. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Unclear risk | 5 (7.1%) withdrawals after randomisation; distribution of withdrawals between study groups not reported |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: inpatient ward of a tertiary care teaching hospital in India Inclusion criteria: infants aged 1 to 24 months, hospitalised with moderate (clinical severity score 3 to 6) acute bronchiolitis, defined as the first episode of wheezing along with prodrome of upper respiratory tract infection Exclusion criteria: children with obtunded consciousness, cardiac disease, chronic respiratory disease, previous wheezing episode, progressive respiratory distress requiring respiratory support other than supplemental oxygen, use of nebulised hypertonic saline within the previous 12 h | |
| Interventions | Intervention group: nebulised 3% saline (4 mL) plus salbutamol (2.5 mg) Control group: nebulised 0.9% saline (4 mL) plus salbutamol (2.5 mg) The medication was given via a jet nebuliser with tight‐fitting face mask, driven by oxygen flow at 7 L/min, every 4 h until the infant was ready for discharge. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding: none The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation |
| Allocation concealment (selection bias) | Low risk | Study solutions were similar in colour, smell, and other physical properties. The code of the therapeutic package (hypertonic saline versus normal saline solution) was deposited with the statistician. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 2 (0.8%) withdrawals after randomisation in normal saline group |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: paediatric inpatient ward, Wolfson Medical Center, Israel Inclusion criteria: infants with clinical presentation of viral bronchiolitis leading to hospitalisation Exclusion criteria: cardiac disease, chronic respiratory disease, previous wheezing episode, age > 12 months, SaO₂ < 85% on room air, obtunded consciousness and/or progressive respiratory failure requiring mechanical ventilation | |
| Interventions | Intervention group: nebulised 3% saline solution (4 mL) plus 1.5 mg epinephrine Control group: nebulised 0.9% saline solution (4 mL) plus 1.5 mg epinephrine Treatment was given 3 times/day at 8‐hour intervals until the infant was ready for discharge. All inhaled treatments were delivered using an ultrasonic nebuliser (Omron UI, OMRON Matsusaka Co Ltd, Japan). | |
| Outcomes |
| |
| Notes | RSV‐positive: 86% in hypertonic saline group; 75% in normal saline group Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomisation in blocks of 4, using an online randomiser |
| Allocation concealment (selection bias) | Low risk | Study solutions were similar in colour, smell, and other physical properties. The code of the therapeutic package (hypertonic saline versus normal saline solution) was deposited with the statistician. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 3 (6.8%) withdrawals after randomisation (1 hypertonic saline group; 2 normal saline group) |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: inpatient wards of 11 general hospitals and 1 tertiary medical centre in the Netherlands Inclusion criteria: children aged birth to 24 months, hospitalised with mild to severe (Wang clinical severity score ≥ 3) viral bronchiolitis, defined as symptoms of an upper respiratory tract infection with wheezing, tachypnoea, and dyspnoea Exclusion criteria: Wang clinical severity score improved at least 2 points after inhalation of 2.5 mg salbutamol, haemodynamically important congenital heart disease, chronic pre‐existent lung disease, T‐cell immunodeficiency, treatment with corticosteroids, and previous wheezing, (food) allergy, or eczema | |
| Interventions | Intervention groups: Control group: nebulised 0.9% saline (4 mL) plus salbutamol (2.5 mg) The solutions were given via a HOT Top Plus Nebuliser (Intersurgical, Uden, Netherlands) with a tight‐fitting face mask, driven by oxygen flow at 6 to 8 L/min, every 8 h until discharge. | |
| Outcomes |
| |
| Notes | RSV‐positive: 83.7% in 3% saline group; 91.4% in 6% saline group; 88.6% in control group Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Block randomisation (in blocks of 6) |
| Allocation concealment (selection bias) | Low risk | Study solutions were identical in vial packaging, colour, smell, and other physical characteristics. The trial codes were kept by the pharmacist. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 43 (14.7%) withdrawals after randomisation (13 (3% saline group); 18 (6% saline group); 12 (normal saline group)). The reasons for withdrawals were similar between study groups. Intention‐to‐treat and per‐protocol analyses yielded similar results. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: inpatient ward of a children’s hospital in Tunisia Inclusion criteria: children aged 1 to 12 months, hospitalised with moderate (Wang clinical severity score of 3) bronchiolitis, defined as an acute infection of the lower respiratory tract, preceded by or accompanied by fever or rhinitis, or both, and characterised by expiratory wheezing and increased respiratory effort Exclusion criteria: prematurity (gestational age at birth < 34 weeks), underlying chronic cardiac or pulmonary disease (e.g. bronchopulmonary dysplasia, cystic fibrosis), recurrent wheezing, severe respiratory distress (apnoeas, heart rate > 200 beats/minute, respiratory rate > 80 breaths/minute, profound lethargy, duration of illness exceeding 15 days) | |
| Interventions | Intervention groups: Control group: nebulised 0.9% saline (4 mL) The solutions were given via a jet nebuliser with a tight‐fitting face mask, driven by oxygen flow at 6 to 7 L/min, every 4 h until discharge. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation |
| Allocation concealment (selection bias) | Low risk | Study solutions were similar in appearance and smell and were stored in identical syringes, labelled only by a code number. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | 3 (3.1%) withdrawals after randomisation (2 normal saline group, 1 hypertonic saline group) |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, controlled trial | |
| Participants | Setting: paediatric emergency department of Istanbul University, Turkey Inclusion criteria: infants aged 2 to 24 months with acute moderate (Wang clinical severity score of 4 to 8) bronchiolitis, defined as viral respiratory tract infections (coryza, cough, fever) with tachypnoea, respiratory distress with chest recession, wheezing and/or crackles Exclusion criteria: younger than 2 months old, prematurity (less than 36th gestational week), low birthweight (less than 2500 g), history of admission to neonatal ICU due to respiratory distress, history of intubation in the ICU, congenital heart/lung/neurologic or immunologic disease, history of atopic disease or recurrent wheezing, clinical or radiologic findings of bacterial infections, atelectasis or consolidations on X‐ray, and refusal to consent by parents | |
| Interventions | Intervention group: nebulised 3% saline (4 mL); nebulised 3% saline (4 mL) plus adrenaline (0.1 mg/kg) Control group: nebulised 0.9% saline (5 mL); nebulised 0.9% saline (4 mL) plus adrenaline (0.1 mg/kg) All nebulisation therapies were delivered via standard oxygen (6 L/min)‐driven hospital nebulisers, 4 times daily until discharge criteria fulfilled. | |
| Outcomes |
| |
| Notes | Virological identification not available. Funding sources/declarations of interest not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Lottery method for simple randomisation |
| Allocation concealment (selection bias) | Unclear risk | No details provided. |
| Blinding (performance bias and detection bias) | Unclear risk | The trial was stated as double‐blind, but no details were provided. |
| Incomplete outcome data (attrition bias) | Low risk | 6 (1.9%) withdrawals after randomisation (4 normal saline group, 2 hypertonic saline group) |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
| Study characteristics | ||
| Methods | Design: randomised, double‐blind, parallel‐group, controlled trial | |
| Participants | Setting: emergency departments of 2 urban freestanding tertiary children’s hospitals in the USA Inclusion criteria: children younger than 24 months with a primary diagnosis of viral bronchiolitis during bronchiolitis season Exclusion criteria: children with a prior illness with wheezing or bronchodilator use, premature (gestational age < 34 weeks), cyanotic congenital heart disease, chronic lung disease, or tracheostomy | |
| Interventions | Intervention group: nebulised 3% saline (4 mL) Control group: nebulised 0.9% saline (4 mL) The solutions were given via a small‐volume wall nebuliser at study entry. Emergency department physicians could order 2 additional treatments every 20 minutes to a maximum of 3 inhaled doses. Admitted infants continued receiving study medication every 8 h until discharge. | |
| Outcomes |
| |
| Notes | RSV‐positive: 65.6% hypertonic saline group; 59.2% normal saline group Supported by grant 02826‐3 from the Thrasher Research Fund and by a Mentored Junior Faculty Career Development Award from the Department of Pediatrics, University of Southern California Keck School of Medicine. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The authors declare no conflicts of interest. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Computer‐generated randomisation |
| Allocation concealment (selection bias) | Low risk | Saline solutions were prepared by the investigational pharmacy and stored in sequentially numbered identical vials. |
| Blinding (performance bias and detection bias) | Low risk | Double‐blind |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawals reported at emergency department setting. |
| Selective reporting (reporting bias) | Low risk | All outcome measures and analyses listed in the methods section reported. |
| Other bias | Low risk | No other bias found. |
CI: confidence interval
ICU: intensive care unit
pCO₂: partial pressure of carbon dioxide
RDAI: Respiratory Distress Assessment Instrument
RSV: respiratory syncytial virus
SaO₂: oxygen saturation
SD: standard deviation
Characteristics of excluded studies [ordered by study ID]
| Study | Reason for exclusion |
| Not an RCT. The authors classified the study design as "prospective case second multicenter study" in the Abstract and "Prospective comparison study" in the Methods. We contacted the first author for more details about study design, but did not receive a reply. | |
| Study of drug delivery (hood versus face mask) | |
| Abstract available only | |
| Other comparison (hypertonic saline versus high‐flow therapy) | |
| Other comparison (epinephrine versus placebo) | |
| Abstract available only | |
| Inclusion of infants with previous history of wheezing | |
| Other comparison (hypertonic saline + 0.1% hyaluronic acid versus 0.9% saline) | |
| Not an RCT | |
| Inclusion of infants with previous history of wheezing | |
| Not an RCT (comment on Morikawa 2017) | |
| Not an RCT (comment on Sarrell 2002) |
RCT: randomised controlled trial
Characteristics of studies awaiting classification [ordered by study ID]
| Methods | Randomised, double‐blind, parallel‐group, controlled trial |
| Participants | Consecutive patients with moderate to severe bronchiolitis, aged 2 months to 2 years, of either sex, admitted to the hospital during the study period |
| Interventions | Nebulised hypertonic saline versus nebulised normal saline |
| Outcomes | Primary outcome:
Secondary outcomes:
|
| Notes | Starting date: July 2009 |
| Methods | Randomised, double‐blind, parallel‐group, controlled trial |
| Participants | Infants under the age of 12 months with a clinical diagnosis of bronchiolitis |
| Interventions | Nebulised 3% saline plus salbutamol |
| Outcomes | Primary outcome:
Secondary outcome:
|
| Notes | Starting date: May 2010 |
| Methods | Randomised, parallel‐group, controlled trial |
| Participants | Children aged 2 months to 24 months, admitted to a teaching hospital, with history of preceding viral upper respiratory infection (fever > 38 °C or coryza), first episode of respiratory distress associated with wheezing, clinical severity score > 3, and no evidence of bacterial infection |
| Interventions | Nebulised 3% saline (4 mL) Nebulised 0.9% saline (4 mL) Nebulised 0.9% saline (4 mL) plus salbutamol (0.15 mg/kg, minimum dose 1 mg) Study solutions were given via a nebuliser driven by oxygen flow at 8 L/min, every 6 h until discharge. |
| Outcomes |
|
| Notes | Suspected plagiarism. This trial presented results identical to those of the Malik 2015 trial. We contacted the first authors of both trials and the editors of the journals in which the trials were published, but neither authors nor editors provided clarification. |
| Methods | Randomised, parallel‐group, controlled trial |
| Participants | Children aged 1 to 24 months, admitted to a teaching hospital, with clinical diagnosis of acute bronchiolitis and clinical severity score > 3 |
| Interventions | Nebulised 3% saline (4 mL) Nebulised 0.9% saline (4 mL) Nebulised salbutamol (0.15 mg/kg) Study solutions were given via a nebuliser driven by oxygen flow at 8 L/min, every 6 h until discharge. |
| Outcomes |
|
| Notes | Suspected plagiarism. This trial presented results identical to those of the Gupta 2016 trial. We contacted the first authors of both trials and the editors of the journals in which the trials were published, but neither authors nor editors provided clarification. |
| Methods | Randomised, double‐blind, parallel‐group, controlled trial |
| Participants | Infants aged up to 24 months, presenting to ED or outpatient department with moderately severe viral bronchiolitis defined as history of viral upper respiratory tract infection within previous 7 days, presence of wheezing or crackles, or both, on chest auscultation, and RDAI score > 4 (of 17) or transcutaneous oxygen saturation < 94% in room air |
| Interventions | Nebulised 3% saline (4 mL) plus 1.0 mg salbutamol Nebulised 0.9% saline (4 mL) plus 1.0 mg salbutamol Study solutions were given every 20 minutes for a total of 3 doses. |
| Outcomes | Primary outcome:
Secondary outcome:
|
| Notes | Starting date: June 2008 |
| Methods | Randomised, double‐blind, parallel‐group, controlled trial |
| Participants | Children aged 6 weeks to 12 months with first moderate to severe episode of acute viral bronchiolitis (history of viral upper respiratory tract infection plus wheezing or crackles, or both, on chest auscultation with respiratory distress), admitted in ED |
| Interventions | Nebulised 3% saline (4 mL) Nebulised 0.9% saline (4 mL) 2 doses of study solutions were given every 20 minutes. |
| Outcomes | Primary outcome:
Secondary outcomes:
|
| Notes | Starting date: October 2012 |
| Methods | Randomised, double‐blind, parallel‐group, controlled trial |
| Participants | Children under 2 years of age diagnosed with mild to moderate bronchiolitis, presenting to outpatient Department of Hospital General Naval de Alta Especialidad, Mexico |
| Interventions | Intervention 1: epinephrine and dexamethasone Intervention 2: 3% saline Active comparator: 0.9% saline |
| Outcomes | Primary outcome:
Secondary outcomes:
|
| Notes | Starting date: January 2013 |
| Methods | Randomised, double‐blind, parallel‐group, controlled trial |
| Participants | Children aged 2 to 12 months, presenting to ED with a diagnosis of bronchiolitis (RDAI score = 6), defined as the first episode of wheezing or crackles, or both, in a child younger than 12 months who has physical findings of a viral respiratory infection and there is no other explanation for the wheezing and/or crackles |
| Interventions | Nebulised 3% saline (3 mL) Nebulised 0.9% saline (3 mL) A single dose of study solution was given. |
| Outcomes | Primary outcome:
Secondary outcomes:
|
| Notes | Starting date: December 2013 |
| Methods | Randomised, double‐blind, parallel‐group, controlled trial |
| Participants | Children aged up to 12 months with clinical diagnosis of bronchiolitis (viral respiratory disease and first episode of wheezing) and with moderate respiratory distress, defined as having at least 2 of the following criteria: SaO₂ < 93%, respiratory rate > 60, and/or RDAI score > 4 |
| Interventions | Nebulised 3% saline (5 mL) Nebulised 0.9% saline (5 mL) Study solutions were initially given every 2 hours, then every 4 hours if the following criteria were met: SaO₂ > 94%, respiratory rate < 60, and RDAI score < 4. |
| Outcomes | Primary outcomes:
Secondary outcomes:
|
| Notes | Starting date: July 2013 |
| Methods | Randomised, double‐blind, parallel‐group, controlled trial |
| Participants | Children aged 2 to 24 months attending the paediatric emergency service with moderate to severe bronchiolitis, defined as first episode of wheezing associated with respiratory distress and a history of upper respiratory tract infection |
| Interventions | Nebulised 3% saline (4 mL) plus salbutamol (100 μg/kg) Nebulised 0.9% saline (4 mL) plus salbutamol (100 μg/kg) 3 doses of study solutions were initially given at an interval of 20 minutes, then every 4 hours during the entire hospital stay. |
| Outcomes | Primary outcomes:
Secondary outcomes:
|
| Notes | Starting date: August 2013 |
| Methods | Randomised, single‐blind (investigator), parallel‐group, controlled trial |
| Participants | Children aged 3 to 18 months, presenting to Children's Hospital Colorado Emergency Department with diagnosis of bronchiolitis and persistent hypoxia following initial supportive care |
| Interventions | Nebulised 3% saline (4 mL) plus standard care Standard care alone A single dose of study solution was given. |
| Outcomes | Primary outcomes:
Secondary outcomes:
|
| Notes | Starting date: September 2013 |
CBSS: Clinical Bronchiolitis Severity Score
ED: emergency department
RDAI: Respiratory Distress Assessment Instrument
SaO₂: oxygen saturation
Data and analyses
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Length of hospital stay (days) Show forest plot | 21 | 2479 | Mean Difference (IV, Random, 95% CI) | ‐0.40 [‐0.69, ‐0.11] |
| Analysis 1.1  Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 1: Length of hospital stay (days) | ||||
| 1.1.1 Hypertonic saline plus salbutamol/albuterol versus normal saline plus salbutamol/albuterol | 12 | 1404 | Mean Difference (IV, Random, 95% CI) | ‐0.13 [‐0.48, 0.22] |
| 1.1.2 Hypertonic saline plus epinephrine versus normal saline plus epinephrine or normal saline alone | 5 | 348 | Mean Difference (IV, Random, 95% CI) | ‐0.65 [‐1.01, ‐0.29] |
| 1.1.3 Hypertonic saline alone versus normal saline alone | 4 | 436 | Mean Difference (IV, Random, 95% CI) | ‐1.13 [‐1.60, ‐0.66] |
| 1.1.4 Hypertonic saline versus standard treatment | 1 | 291 | Mean Difference (IV, Random, 95% CI) | 0.06 [‐0.62, 0.74] |
| 1.2 Rate of hospitalisation Show forest plot | 8 | 1760 | Risk Ratio (M‐H, Random, 95% CI) | 0.87 [0.78, 0.97] |
| Analysis 1.2  Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 2: Rate of hospitalisation | ||||
| 1.2.1 Hypertonic saline plus bronchodilator versus normal saline plus bronchodilator | 5 | 458 | Risk Ratio (M‐H, Random, 95% CI) | 0.78 [0.55, 1.10] |
| 1.2.2 Hypertonic saline alone versus normal saline alone | 4 | 1302 | Risk Ratio (M‐H, Random, 95% CI) | 0.87 [0.69, 1.08] |
| 1.3 Clinical severity score (post‐treatment) at day 1 Show forest plot | 10 | 893 | Mean Difference (IV, Random, 95% CI) | ‐0.64 [‐1.08, ‐0.21] |
| Analysis 1.3  Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 3: Clinical severity score (post‐treatment) at day 1 | ||||
| 1.3.1 Outpatients | 1 | 65 | Mean Difference (IV, Random, 95% CI) | ‐1.28 [‐1.92, ‐0.64] |
| 1.3.2 Emergency department patients | 1 | 171 | Mean Difference (IV, Random, 95% CI) | ‐0.09 [‐0.51, 0.33] |
| 1.3.3 Inpatients | 8 | 657 | Mean Difference (IV, Random, 95% CI) | ‐0.64 [‐1.15, ‐0.13] |
| 1.4 Clinical severity score (post‐treatment) at day 2 Show forest plot | 10 | 907 | Mean Difference (IV, Random, 95% CI) | ‐1.07 [‐1.60, ‐0.53] |
| Analysis 1.4  Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 4: Clinical severity score (post‐treatment) at day 2 | ||||
| 1.4.1 Outpatients | 1 | 65 | Mean Difference (IV, Random, 95% CI) | ‐2.00 [‐2.93, ‐1.07] |
| 1.4.2 Emergency department patients | 1 | 171 | Mean Difference (IV, Random, 95% CI) | ‐0.27 [‐0.63, 0.09] |
| 1.4.3 Inpatients | 8 | 671 | Mean Difference (IV, Random, 95% CI) | ‐1.08 [‐1.68, ‐0.47] |
| 1.5 Clinical severity score (post‐treatment) at day 3 Show forest plot | 10 | 785 | Mean Difference (IV, Random, 95% CI) | ‐0.89 [‐1.44, ‐0.34] |
| Analysis 1.5  Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 5: Clinical severity score (post‐treatment) at day 3 | ||||
| 1.5.1 Outpatients | 1 | 65 | Mean Difference (IV, Random, 95% CI) | ‐2.64 [‐3.85, ‐1.43] |
| 1.5.2 Inpatients | 9 | 720 | Mean Difference (IV, Random, 95% CI) | ‐0.74 [‐1.31, ‐0.18] |
| 1.6 Rate of readmission to hospital Show forest plot | 6 | 1084 | Risk Ratio (M‐H, Random, 95% CI) | 0.83 [0.55, 1.25] |
| Analysis 1.6  Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 6: Rate of readmission to hospital | ||||
| 1.7 Number of days to resolution of symptoms and signs (days) Show forest plot | 3 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| Analysis 1.7  Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 7: Number of days to resolution of symptoms and signs (days) | ||||
| 1.7.1 Wheezing | 2 | 205 | Mean Difference (IV, Random, 95% CI) | ‐1.16 [‐1.43, ‐0.89] |
| 1.7.2 Cough | 3 | 363 | Mean Difference (IV, Random, 95% CI) | ‐0.87 [‐1.31, ‐0.44] |
| 1.7.3 Pulmonary moist crackles | 2 | 205 | Mean Difference (IV, Random, 95% CI) | ‐1.30 [‐2.28, ‐0.32] |
| 1.8 Duration of in‐hospital oxygen supplementation (hours) Show forest plot | 3 | 269 | Mean Difference (IV, Random, 95% CI) | ‐0.25 [‐9.36, 8.86] |
| Analysis 1.8  Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 8: Duration of in‐hospital oxygen supplementation (hours) | ||||
| 1.9 Radiological assessment score Show forest plot | 2 | 117 | Mean Difference (IV, Random, 95% CI) | ‐0.08 [‐0.90, 0.75] |
| Analysis 1.9  Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 9: Radiological assessment score | ||||
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Funnel plot of the weighted mean difference (WMD) of length of hospital stay (days) against its standard error. The circles represent risk estimates of each study, and the black vertical line represents the pooled effect estimate. Dashed lines represent pseudo‐95% confidence limits. Egger test (P = 0.38) suggests no small‐study effects.
Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 1: Length of hospital stay (days)
Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 2: Rate of hospitalisation
Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 3: Clinical severity score (post‐treatment) at day 1
Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 4: Clinical severity score (post‐treatment) at day 2
Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 5: Clinical severity score (post‐treatment) at day 3
Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 6: Rate of readmission to hospital
Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 7: Number of days to resolution of symptoms and signs (days)
Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 8: Duration of in‐hospital oxygen supplementation (hours)
Comparison 1: Hypertonic saline versus normal saline or standard treatment, Outcome 9: Radiological assessment score
| Nebulised hypertonic saline compared with nebulised 0.9% saline for acute bronchiolitis in infants | ||||||
| Patient or population: infants up to 24 months of age with acute bronchiolitis Settings: outpatient, emergency department, or inpatient Intervention: nebulised hypertonic saline (≥ 3%) Comparison: nebulised 0.9% saline or no intervention | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | Number of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk** | Corresponding risk | |||||
| Nebulised normal saline | Nebulised hypertonic saline | |||||
| Length of hospital stay (days)
| The mean length of hospital stay ranged across control groups from 1.8 to 7.4 days. | The mean length of hospital stay in the intervention groups was on average 0.40 days shorter (95% CI −0.69 to −0.11).
| ‐ | 2479 (21 trials) | ⊕⊕⊝⊝ | The effect size of nebulised hypertonic saline shown in this 2022 updated review, as well as in the 2017 review, was only approximately one‐third of that shown in the 2013 review, which included 6 inpatient trials involving 500 infants (MD −1.15 days, 95% CI −1.49 to −0.82 days). All but 2 trials published in 2013 and after, including 2 European multicentre studies, did not find significant effects of hypertonic saline on length of stay amongst inpatients with acute bronchiolitis. Despite the effects of nebulised hypertonic saline on reduction in length of hospital stay being smaller than were estimated previously, a reduction of almost 10 hours in length of hospital stay in infants with bronchiolitis may still be considered clinically relevant given the relatively short disease course, high prevalence, and huge burden of illness on healthcare systems around the world. |
| Clinical severity score (post‐treatment) at day 1 Assessed with: Wang clinical severity score Scale from 0 to 12 (lower = better) | The mean clinical severity score ranged across control groups from 1.9 to 8.8. | The mean clinical severity score in the intervention groups was on average 0.64 lower (95% CI −1.08 to −0.21). | ‐ | 893 (10 trials: 1 outpatient, 1 ED, 8 inpatients) | ⊕⊕⊝⊝
| The meta‐analysis was based on data from only 10 trials, with reduced number of participants. The reduction of 0.64 in clinical score represents 11% of the mean score in the control group. |
| Clinical severity score (post‐treatment) at day 2 Assessed with: Wang clinical severity score Scale from 0 to 12 (lower = better) | The mean clinical severity score ranged across control groups from 0.8 to 8.2. | The mean clinical severity score in the intervention groups was on average 1.07 lower (95% CI −1.60 to −0.53). | ‐ | 907 (10 trials: 1 outpatient, 1 ED, 8 inpatient) | ⊕⊕⊝⊝
| The meta‐analysis was based on data from only 10 trials, with reduced number of participants. The reduction of 1.07 in clinical score represents 21% of the mean score in the control group. |
| Clinical severity score (post‐treatment) at day 3 Assessed with: Wang clinical severity score Scale from 0 to 12 (lower = better) | The mean clinical severity score ranged across control groups from 0.1 to 7.6. | The mean clinical severity score in the intervention groups was on average 0.89 lower (95% CI −1.44 to −0.34). | ‐ | 785 (10 trials: 1 outpatient, 9 inpatient) | ⊕⊕⊝⊝
| The meta‐analysis was based on data from only 10 trials, with reduced number of participants. The reduction of 0.89 in clinical score represents 22% of the mean score in the control group. |
| Rate of hospitalisation Follow‐up: range 1 to 72 hours after enrolment
| 34 per 100 (15 to 52) | 28 per 100 | RR 0.87 (0.78 to 0.97) | 1760 (8 trials: 1 outpatient, 7 ED) | ⊕⊕⊝⊝ | 2 trials contributed 73% of weight to the overall summary estimate of effects (Angoulvant 2017; Wu 2014). |
| Rate of readmission to hospital Follow‐up: up to 28 days after discharge
| 15 per 100 (4 to 25) | 13 per 100 (7 to 19) | RR 0.83 (0.55 to 1.25) | 1084 (6 trials: 1 inpatient, 5 ED) | ⊕⊕⊝⊝ | The meta‐analysis was based on data from only 6 trials, with reduced number of participants. |
| Number of days to resolution of symptoms and signs (wheezing) Follow‐up: during hospitalisation | The mean time to resolution ranged across control groups from | The mean time to resolution in the intervention groups was on average 1.16 days shorter (95% CI −1.43 to −0.89). | ‐ | 205 | ⊕⊝⊝⊝ | The meta‐analysis was based on data from only 2 trials (of the same research group), with reduced number of participants. |
| Number of days to resolution of symptoms and signs (cough) Follow‐up: during hospitalisation | The mean time to resolution ranged across control groups from | The mean time to resolution in the intervention groups was on average 0.87 days shorter | ‐ | 363 | ⊕⊝⊝⊝ | The meta‐analysis was based on data from only 3 trials, with reduced number of participants. |
| Number of days to resolution of symptoms and signs(pulmonary moist crackles) Follow‐up: during hospitalisation | The mean time to resolution ranged across control groups from 6.2 to 6.2 days. | The mean time to resolution in the intervention groups was on average 1.30 days shorter | ‐ | 205 | ⊕⊝⊝⊝ | The meta‐analysis was based on data from only 2 trials (of the same research group), with reduced number of participants. |
| Adverse events Assessed by investigators or reported by parents Follow‐up: during and immediately after nebulisation | See comment | See comment | Not estimable | 4416 (2246 received hypertonic saline) (27 trials) | ⊕⊕⊝⊝ | 14 trials (1624 infants, 767 treated with hypertonic saline) did not report any adverse events, and 13 trials (2792 infants, 1479 treated with hypertonic saline) reported at least 1 adverse event; most adverse events were mild and resolved spontaneously. |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; ED: emergency department; MD: mean difference; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence | ||||||
| aWe downgraded the certainty of the evidence to low due to inconsistent results between studies (high heterogeneity) and risk of bias. | ||||||
| Study ID | Saline concentration | Saline volume | Bronchodilator administered | Administration interval | Treatment duration |
|---|---|---|---|---|---|
| Outpatient trials | |||||
| 3%, 5% | 3 mL | None | Twice daily | 3 days | |
| 3% | 2 mL | Terbutaline 5 mg | Every 8 hours | 5 days | |
| Emergency department trials | |||||
| 3%, 5% | 5 mL | Epinephrine 1.5 mL | Every 4 hours | Until discharge | |
| 3% | 4 mL | None | Study solution was given at 0 and 30 minutes. | Until 2 doses had been administered | |
| 3% | 4 mL | Epinephrine 1.5 mL or salbutamol 2.5 mg | Every 30 minutes | Until 2 doses had been administered | |
| 3% | 4 mL | None | Within 90 minutes after albuterol administration | Single dose | |
| 3% | 2.5 mL | 2.25% racaemic epinephrine 0.5 mL | If needed, the second dose was given during the 120‐minute study period. | Up to 2 doses | |
| 3% | 4 mL | Salbutamol 0.15 mg/kg | Every 20 minutes | Until 3 doses had been administered | |
| 7% | 3 mL | Racaemic epinephrine 0.5 mL | Study solution was given after initial screening and assessment. | Single dose (if the infant was admitted, the same solution was given every 6 h until discharge or 24 h after the admission) | |
| 3% | 4 mL | Epinephrine 1.5 mg | Study solution was given at 0 and 30 minutes. | Until 2 doses had been administered | |
| 3% | 4 mL | None | 4 times daily | Until discharge criteria were fulfilled | |
| 3% | 4 mL | None | Emergency department physicians could order 2 additional doses every 20 minutes. | Up to 3 doses | |
| Inpatient trials | |||||
| 3% | 3.5 mL | Salbutamol 2.5 mg (0.5 mL) | Every 6 hours | Until clinical severity score ≤ 4 | |
| 3% | 4 mL | None | Every 2 hours for 3 doses, followed by every 4 hours for 6 doses, then every 6 hours | Until discharge | |
| 3% | 4 mL | None | Every 6 hours | Until fit for discharge | |
| 3% | 3 mL | Salbutamol 0.25 mL (1.25 mg) | Every 6 hours | Until discharge | |
| 3% | 3 mL | Salbutamol (?) mL | Every 6 hours | Until discharge | |
| 3% | 4 mL | None | Every 6 hours | Until discharge | |
| 3%, 7% | 2.5 mL | Salbutamol 0.15 mg/kg | 2 doses were given at 30‐minute interval, followed by every 6 hours. | Until discharge | |
| 3% | 4 mL | Albuterol was added in 37% of the treatments, and racaemic epinephrine was added in 23% of the treatments by attending physicians. | Every 2 hours for 3 doses, followed by every 4 hours for 5 doses, then every 6 hours | Until discharge | |
| 3% | 4 mL | Salbutamol 2.5 mg | Every 8 hours | Until discharge | |
| 3% | 4 mL | None | Every 2 hours for 3 doses, followed by every 4 hours for 5 doses, then every 6 hours | Until discharge | |
| 3% | 3 mL | Salbutamol 0.15 mg/kg | Every 6 hours | Until ready for discharge | |
| 3% | 4 mL | Epinephrine 1.5 mg | Every 8 hours | Until discharge | |
| 3% | ? mL | Epinephrine 1.5 mg | Every 6 hours | Until discharge | |
| 3% | 2 mL | 0.5% salbutamol 0.1 mL | 4 times daily | Until discharge criteria were fulfilled | |
| 3% | 3 mL | Albuterol 0.25 mg/kg/day | 4 times a day | 5 days | |
| 3% | 4 mL | None | Every 8 hours | Until discharge | |
| 3% | 4 mL | Epinephrine 1.0 mL | 3 doses were given at 1‐hour intervals, followed by every 6 hours. | Until discharge | |
| 3% | 3 mL | Salbutamol 0.15 mg/kg | Every 4 hours | Until discharge | |
| 3% | 4 mL | Salbutamol 2.5 mg | Every 4 hours | Until ready for discharge | |
| 3% | 4 mL | Epinephrine 1.5 mg | Every 8 hours | Until discharge | |
| 3%, 6% | 4 mL | Salbutamol 2.5 mg | Every 8 hours | Until discharge | |
| 5% | 4 mL | Epinephrine 2 mL | Every 4 hours | Until discharge | |
| Subgroups | Length of hospital stay (days) | ||||
|---|---|---|---|---|---|
| Trial (n) | Participants (N) | Effect size (MD, 95% CI) | P values for subgroup difference (Chi²) | Heterogeneity (I²) | |
| Virological investigation | |||||
| Available Not available | 11 10 | 1307 1172 | −0.51 (−1.02 to 0.002) −0.28 (−0.67 to 0.10) | 0.49 | 84% 85% |
| Upper age limits for infants | |||||
| 12 months 18 to 24 months | 7 14 | 773 1706 | −0.27 (−0.63 to 0.09) −0.43 (−0.79 to −0.07) | 0.55 | 15% 89% |
| Hypertonic saline solution plus bronchodilator | |||||
| β₂ agonist Epinephrine No | 12 5 4 | 1424 404 651 | −0.19 (−0.57 to 0.17) −0.65 (−1.01 to −0.30) −0.63 (−1.28 to 0.01) | 0.18 | 79% 0% 89% |
| Administration interval* | |||||
| A B | 16 5 | 1987 492 | −0.38 (−0.69 to −0.06) −0.51 (−1.33 to 0.32) | 0.77 | 82% 88% |
| Hypertonic saline concentration** | |||||
| 3% > 3% | 20 3 | 2037 442 | −0.40 (−0.70 to −0.09) 0.12 (−0.54 to 0.77) | 0.16 | 86% 33% |
| Length of stay in the control group | |||||
| < 3 days ≥ 3 days | 6 15 | 884 1595 | −0.08 (−0.64 to 0.47) −0.56 (−0.90 to −0.23) | 0.15 | 93% 68% |
| Risk of bias in any domain | |||||
| Low Unclear/high | 8 13 | 1001 1478 | −0.35 (−0.93 to 0.23) −0.45 (−0.76 to −0.14) | 0.76 | 87% 73% |
| Year of publication | |||||
| Before 2013 2013 and after | 7 14 | 577 1902 | −0.98 (−1.41 to −0.55) −0.14 (−0.48 to 0.20) | 0.003 | 59% 84% |
| CI: confidence interval *Regimen A: every 4 to 6 hours; regimen B: every 8 hours | |||||
| Length of hospital stay (days) | |||
|---|---|---|---|
| Effect size | Heterogeneity | Trials excluded from analysis | Reasons for exclusion |
| −0.46 (−0.74 to −0.18) | 81% | Mean and standard deviation were estimated from median and interquartile range. | |
| −0.28 (−0.58 to 0.01) | 80% | Very short (< 2 days) or very long (> 6 days) length of stay in the control group | |
| CI: confidence interval | |||
| Subgroups | Hospitalisation rate (%) | ||||
|---|---|---|---|---|---|
| Trial (n) | Participants (N) | Effect size (RR, 95% CI) | P values for subgroup difference (Chi²) | Heterogeneity | |
| Virological investigation | |||||
| Available Not available | 5 3 | 1392 368 | 0.82 (0.69 to 0.97) 1.05 (0.76 to 1·45) | 0.19 | 21% 0% |
| Upper age limits for infants | |||||
| 12 months 18 to 24 months | 2 6 | 818 942 | 0.86 (0.64 to 1.15) 0.82 (0.67 to 1.02) | 0.75 | 26% 0% |
| Hypertonic saline solution plus bronchodilator* | |||||
| β₂ agonist Epinephrine No | 3 3 3 | 276 242 1242 | 0.62 (0.26 to 1.48) 0.80 (0.56 to 1.14) 0.87 (0.69 to 1.11) | 0.72 | 0% 0% 66% |
| Administration interval** | |||||
| A B | 2 6 | 163 1597 | 1.0 (0.78 to 1.31) 0.85 (0.75 to 0.96) | 0.27 | 0% 0% |
| Hypertonic saline concentration | |||||
| 3% > 3% | 7 1 | 1659 101 | 0.86 (0.74 to 0.99) 0.86 (0.56 to 1.32) | 0.94 | 20% ‐ |
| Risk of bias in any domain | |||||
| Low Unclear/high | 4 4 | 1288 472 | 0.85 (0.68 to 1.06) 0.82 (0.56 to 1.21) | 0.91 | 57% 0% |
| Year of publication | |||||
| Before 2013 2013 and after | 4 4 | 417 1343 | 0.64 (0.38 to 1.08) 0.87 (0.72 to 1.05) | 0.28 | 0% 49% |
| CI: confidence interval *Anil 2010 used two intervention groups: hypertonic saline plus salbutamol and hypertonic saline plus epinephrine. | |||||
| Trials | Comparisons | Narrative summary |
|---|---|---|
| 3% saline (N = 47) vs 0.9% saline (N = 49) | No infants were withdrawn by the medical staff due to AEs, although 5 infants were withdrawn at parents’ request due to perceived AEs, only 2 of which were in the hypertonic saline group (1 presented with vigorous crying and another with agitation). | |
| 3% saline + epinephrine (N = 23) vs 0.9% saline + epinephrine (N = 23) | Adverse events were noted in 4 infants (vomiting 3; diarrhoea 1) in the hypertonic saline group. No additional bronchodilators were given to any enrolled infant during the study period. | |
| 3% saline (N = 57) vs 0.9% saline (N = 55) | No infants were withdrawn by the medical staff due to AEs. Coughing and wheezing did not worsen during saline inhalation. Although 5 infants had hoarse voices, only 2 of these were in the hypertonic saline group, and the symptom disappeared after 3 to 4 days. | |
| 3% saline + epinephrine (N = 51) vs 0.9% saline + epinephrine (N = 49) | No AEs were observed in the 3% saline group. In the 0.9% saline group, 3 infants had vomiting, and 1 infant had diarrhoea. | |
| 3% saline (N = 142) vs standard care (N = 143) | 6 AEs were possibly related to saline treatment, including 1 SAE, bradycardia and desaturation, which resolved the following day. The remaining 5 non‐SAEs were: bradycardia (self‐correcting), desaturation, coughing fit, and increased respiratory rate (all of which resolved within 1 day), and a chest infection, which resolved after 6 days. | |
| 5% saline (N = 40), 3% saline (N = 42) vs 0.9% saline (N = 42) | No AEs were observed in the 3% and 0.9% saline groups. 4 infants in the 5% saline group presented with paroxysmal cough during saline inhalation. | |
| 3%, 6% saline + salbutamol (N = 167) vs 0.9% saline + salbutamol (N = 80) | A substantial number of AEs (cough, bronchospasm, agitation, desaturation, etc.) were noted in all treatment groups. Except for cough, which occurred more significantly in the hypertonic saline groups (P = 0.03), no differences were found between groups. Withdrawals due to AEs did not differ between groups (4.3%, 6.1%, and 7.9% in the 3%, 6%, and 0.9% saline groups, respectively; P = 0.59). | |
| 3% saline (N = 211) vs 0.9% saline (N = 197) | 3 infants in the normal saline group and 4 infants in the hypertonic saline group withdrew due to parent request. Of these parent requests, 1 in the normal saline group and 2 in the hypertonic saline group were attributed to worsening cough. For these 3 infants, pre‐treatment and post‐treatment vital signs and Respiratory Distress Assessment Instrument score were the same or improved, and no intervention or additional treatment was necessary. | |
| 3% saline + salbutamol (N = 33) vs 0.9% saline + salbutamol (N = 35) | Exacerbation of coughing and excessive rhinorrhoea were more common in the 3% saline group (45.5% and 57.6%) than in the 0.9% saline group (20% and 31.4%). There was no significant difference in bronchial constriction and agitation between groups. Apnoea, cyanosis, saturation dips, tachycardia, and vomiting were not observed. | |
| 3% saline + salbutamol (N = 35), 7% saline + salbutamol (N = 32) vs 0.9% saline + salbutamol (N = 35) | No AEs were reported in the 3% and 0.9% saline groups. In the 7% saline group, bronchospasm was observed in 2 infants, and exacerbation of coughing was observed in another 2 infants. Both bronchospasm and cough were observed during nebulisation in 1 infant. | |
| 3% saline (N = 385) vs 0.9% saline (N = 387) | No SAEs were reported. Mild AEs occurred 57 times amongst 50 infants, in 35 of 392 infants (8.9%) in the HS group versus 15 of 384 infants (3.9%) in the NS group (risk difference 5.0%, 95% confidence interval 1.6% to 8.4%; P = 0.005). Worsening of cough without respiratory distress was the most frequent AE, occurring in 26 infants (6.6%) in the HS group and 3 infants (0.8%) in the NS group. Bronchospasm occurred in 3 infants (0.8%) in the NS group. | |
| 3% saline (N = 79) and 3% saline + epinephrine (N = 75) vs 0.9% saline (N = 82) and 0.9% saline + epinephrine (N = 76) | Adverse events (tachycardia, pallor, tremor, nausea or vomiting) were reported in 5 infants in the hypertonic saline group and 9 infants in the normal saline group. | |
| 3% saline + standard care (N = 60) vs standard care only (N = 60) | No SAEs (bronchospasm, excessive coughing, infection, apnoea and cyanosis) were observed during the study. However, HS was discontinued in 10 infants at parents’ request (sleep preservation, N = 5; agitation with the inhalation face mask, N = 5). | |
| AE: adverse event | ||
| Review | Trials included | Participants | Hospital length‐of‐stay reduction | Clinical score reduction | Days to resolution of symptoms and signs reduction (MD, 95% CI) | Hospitalisation rate reduction | Readmission rate reduction | Other findings |
|---|---|---|---|---|---|---|---|---|
| 11 | 1070 (infants with previous wheeze excluded) | −0.96 days (−1.38 to −0.54) (6 trials) | Day 1: −0.77 (−1.30 to −0.24) Day 2: −0.85 (−1.30 to −0.39) Day 3: −1.14 (−1.69 to −0.58) (6 trials) | ‐ | 0.59 (0.37 to 0.93) (5 trials) | 1.08 (0.68 to 1.73) (3 trials) | None | |
| 19 | 2441 | −0.42 days (−0.72 to −0.11) (19 trials) | ‐ | ‐ | ‐ | ‐ | ‐ | |
| 15 | 1922 | −0.36 days (−0.50 to −0.22) (15 trials) | −1.36 (−1.52 to −1.20) (5 trials) | ‐ | ‐ | ‐ | ‐ | |
| 28 | 4195 (infants with previous wheeze excluded) | −0.41 days (−0.75 to −0.07) (17 trials) | Day 1: −0.77 (−1.18 to −0.36) (9 trials) Day 2: −1.28 (−1.91 to −0.65) (8 trials) Day 3: −1.43 (−1.82 to −1.04) (7 trials) | Wheezing: −1.16 days (−1.43 to −0.89) (2 trials) Cough: −1.01 days (−1.35 to −0.66) (2 trials) Pulmonary moist crackles: −1.30 days (−2.28 to −0.32) (2 trials) | 0.86 (0.76 to 0.98) (8 trials) | Readmission to 0.77 (0.48 to 1.25) (6 trials) | No significant difference between the hypertonic saline group and the control group in terms of oxygen saturation, duration of oxygen supplementation, respiratory rate, heart rate, and radiograph scores | |
| CI: confidence interval | ||||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Length of hospital stay (days) Show forest plot | 21 | 2479 | Mean Difference (IV, Random, 95% CI) | ‐0.40 [‐0.69, ‐0.11] |
| 1.1.1 Hypertonic saline plus salbutamol/albuterol versus normal saline plus salbutamol/albuterol | 12 | 1404 | Mean Difference (IV, Random, 95% CI) | ‐0.13 [‐0.48, 0.22] |
| 1.1.2 Hypertonic saline plus epinephrine versus normal saline plus epinephrine or normal saline alone | 5 | 348 | Mean Difference (IV, Random, 95% CI) | ‐0.65 [‐1.01, ‐0.29] |
| 1.1.3 Hypertonic saline alone versus normal saline alone | 4 | 436 | Mean Difference (IV, Random, 95% CI) | ‐1.13 [‐1.60, ‐0.66] |
| 1.1.4 Hypertonic saline versus standard treatment | 1 | 291 | Mean Difference (IV, Random, 95% CI) | 0.06 [‐0.62, 0.74] |
| 1.2 Rate of hospitalisation Show forest plot | 8 | 1760 | Risk Ratio (M‐H, Random, 95% CI) | 0.87 [0.78, 0.97] |
| 1.2.1 Hypertonic saline plus bronchodilator versus normal saline plus bronchodilator | 5 | 458 | Risk Ratio (M‐H, Random, 95% CI) | 0.78 [0.55, 1.10] |
| 1.2.2 Hypertonic saline alone versus normal saline alone | 4 | 1302 | Risk Ratio (M‐H, Random, 95% CI) | 0.87 [0.69, 1.08] |
| 1.3 Clinical severity score (post‐treatment) at day 1 Show forest plot | 10 | 893 | Mean Difference (IV, Random, 95% CI) | ‐0.64 [‐1.08, ‐0.21] |
| 1.3.1 Outpatients | 1 | 65 | Mean Difference (IV, Random, 95% CI) | ‐1.28 [‐1.92, ‐0.64] |
| 1.3.2 Emergency department patients | 1 | 171 | Mean Difference (IV, Random, 95% CI) | ‐0.09 [‐0.51, 0.33] |
| 1.3.3 Inpatients | 8 | 657 | Mean Difference (IV, Random, 95% CI) | ‐0.64 [‐1.15, ‐0.13] |
| 1.4 Clinical severity score (post‐treatment) at day 2 Show forest plot | 10 | 907 | Mean Difference (IV, Random, 95% CI) | ‐1.07 [‐1.60, ‐0.53] |
| 1.4.1 Outpatients | 1 | 65 | Mean Difference (IV, Random, 95% CI) | ‐2.00 [‐2.93, ‐1.07] |
| 1.4.2 Emergency department patients | 1 | 171 | Mean Difference (IV, Random, 95% CI) | ‐0.27 [‐0.63, 0.09] |
| 1.4.3 Inpatients | 8 | 671 | Mean Difference (IV, Random, 95% CI) | ‐1.08 [‐1.68, ‐0.47] |
| 1.5 Clinical severity score (post‐treatment) at day 3 Show forest plot | 10 | 785 | Mean Difference (IV, Random, 95% CI) | ‐0.89 [‐1.44, ‐0.34] |
| 1.5.1 Outpatients | 1 | 65 | Mean Difference (IV, Random, 95% CI) | ‐2.64 [‐3.85, ‐1.43] |
| 1.5.2 Inpatients | 9 | 720 | Mean Difference (IV, Random, 95% CI) | ‐0.74 [‐1.31, ‐0.18] |
| 1.6 Rate of readmission to hospital Show forest plot | 6 | 1084 | Risk Ratio (M‐H, Random, 95% CI) | 0.83 [0.55, 1.25] |
| 1.7 Number of days to resolution of symptoms and signs (days) Show forest plot | 3 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.7.1 Wheezing | 2 | 205 | Mean Difference (IV, Random, 95% CI) | ‐1.16 [‐1.43, ‐0.89] |
| 1.7.2 Cough | 3 | 363 | Mean Difference (IV, Random, 95% CI) | ‐0.87 [‐1.31, ‐0.44] |
| 1.7.3 Pulmonary moist crackles | 2 | 205 | Mean Difference (IV, Random, 95% CI) | ‐1.30 [‐2.28, ‐0.32] |
| 1.8 Duration of in‐hospital oxygen supplementation (hours) Show forest plot | 3 | 269 | Mean Difference (IV, Random, 95% CI) | ‐0.25 [‐9.36, 8.86] |
| 1.9 Radiological assessment score Show forest plot | 2 | 117 | Mean Difference (IV, Random, 95% CI) | ‐0.08 [‐0.90, 0.75] |
