5. Narrative summary: adverse events of treatment reported in 11 trials.
| Trials | Comparisions | Narrative summary |
| Everard 2014 | 3% saline (N = 142) versus 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 were resolved within 1 day); and a chest infection, which resolved after 6 days. |
| Flores 2016 | 3% saline + salbutamol (N = 33) versus 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 the 2 groups. Apnoea, cyanosis, saturation dips, tachycardia, and vomiting were not observed. |
| Grewal 2009 | 3% saline + epinephrine (N = 23) versus 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. |
| Köse 2016 | 3% saline + salbutamol (N = 35), 7% saline + salbutamol (N = 32) versus 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 was observed during nebulisation in 1 infant. |
| Kuzik 2007 | 3% saline (N = 47) versus 0.9% saline (N = 49) | No infants were withdrawn by the medical staff due to AEs, although 5 infants were withdrawn at parents’ request due to perceived AEs, only 2 of which were from the hypertonic saline group (1 presented with vigorous crying and another with agitation). |
| Li 2014 | 5% saline (N = 40), 3% saline (N = 42) versus 0.9% saline (N = 42) | No AEs were observed in the 3% and 0.9% saline groups. 4 infants from the 5% saline group presented with paroxysmal cough during saline inhalation. |
| Luo 2011 | 3% saline (N = 57) versus 0.9% saline (N = 55) | No infants were withdrawn by the medical staff due to AEs.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 from the hypertonic saline group, and the symptom disappeared after 3 to 4 days. |
| Pandit 2013 | 3% saline + epinephrine (N = 51) versus 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. |
| Teunissen 2014 | 3%, 6% saline + salbutamol (N = 167) versus 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). |
| Wu 2014 | 3% saline (N = 211) versus 0.9% saline (N = 197) | 3 infants in the normal saline group and 4 infants in the hypertonic saline group withdrew owing 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. |
| Angoulvant 2017 | 3% saline (N = 385) versus 0.9% saline (N = 387) | No SAEs were reported. Mild AEs occurred 57 times among 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. |
Abbreviations: AE: adverse event HS: hypertonic saline NS: normal saline SAE: serious adverse event