Croup (original) (raw)

Abstract

Introduction

Croup is characterised by the abrupt onset, most commonly at night, of a barking cough, inspiratory stridor, hoarseness, and respiratory distress due to upper airway obstruction. It leads to signs of upper airway obstruction, and must be differentiated from acute epiglottitis, bacterial tracheitis, or an inhaled foreign body. Croup affects about 3% of children a year, usually between the ages of 6 months and 3 years, and 75% of infections are caused by parainfluenza virus. Symptoms usually resolve within 48 hours, but severe infection can, rarely, lead to pneumonia, and to respiratory failure and arrest.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments in children with: mild croup; moderate to severe croup; and impending respiratory failure because of severe croup? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 43 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, corticosteroids, dexamethasone (intramuscular, oral, single-dose oral, route of administration), heliox, humidification, intermittent positive pressure breathing, L-adrenaline, nebulised adrenaline (epinephrine), nebulised budesonide, nebulised short-acting beta2 agonists, oral decongestants, oral prednisolone, oxygen, and sedatives.

Key Points

Croup leads to signs of upper airway obstruction, and must be differentiated from acute epiglottitis, bacterial tracheitis, or an inhaled foreign body.

• Croup affects about 3% of children a year, usually between the ages of 6 months and 3 years, and 75% of infections are caused by parainfluenza virus.
• Symptoms usually resolve within 48 hours, but severe infection can, rarely, lead to respiratory failure and arrest.

A single oral dose of dexamethasone improves symptoms in children with mild croup, compared with placebo.

• Although humidification and oral decongestants are often used in children with mild to moderate croup, there is no evidence to support their use in clinical practice.
• There is consensus that antibiotics do not improve symptoms in croup of any severity, as croup is usually viral in origin.

In children with moderate to severe croup, intramuscular or oral dexamethasone, nebulised adrenaline (epinephrine), and nebulised budesonide reduce symptoms compared with placebo.

• Oxygen is standard treatment in children with respiratory distress. Oral dexamethasone is as effective as nebulised budesonide at reducing symptoms, and is less distressing for the child.
• A dexamethasone dose of 0.15 mg/kg may be as effective as a dose of 0.6 mg/kg. Adding nebulised budesonide to oral dexamethasone does not seem to improve efficacy compared with either drug alone.
• Nebulised adrenaline (epinephrine) has a short-term effect on symptoms of croup, but we don't know whether adding intermittent positive-pressure breathing to nebulised adrenaline further improves symptoms.
• We don't know whether heliox (helium–oxygen mixture), humidification, short-acting nebulised beta2 agonists, or oral decongestants are beneficial in children with moderate to severe croup, or with impending respiratory failure.

In children with impending respiratory failure caused by severe croup, nebulised adrenaline (epinephrine) is considered likely to be beneficial. Oxygen is standard treatment.

• Nasogastric prednisolone reduces the need for, or duration of, intubation, but sedatives and antibiotics are unlikely to be beneficial.

About this condition

Definition

Croup is characterised by the abrupt onset, most commonly at night, of a barking cough, inspiratory stridor, hoarseness, and respiratory distress due to upper airway obstruction. Croup symptoms are often preceded by symptoms like those of upper respiratory tract infection. The most important diagnoses to differentiate from croup include bacterial tracheitis, epiglottitis, and the inhalation of a foreign body. Some investigators distinguish subtypes of croup. Those most commonly distinguished are acute laryngotracheitis and spasmodic croup. Children with acute laryngotracheitis have an antecedent upper respiratory tract infection, are usually febrile, and are thought to have more persistent symptoms. Children with spasmodic croup do not have an antecedent upper respiratory tract infection, are afebrile, have recurrent croup, and are thought to have more transient symptoms. However, there is little empirical evidence that spasmodic croup responds differently from acute laryngotracheitis. Population: In this review, we have included children up to the age of 12 years with croup; no attempt has been made to exclude spasmodic croup. We could not find definitions of clinical severity that are either widely accepted or rigorously derived. For this review, we have elected to use definitions derived by a committee consisting of a range of specialists and sub-specialists during the development of a clinical practice guideline from Alberta Medical Association (Canada). The definitions of severity have been correlated with the Westley croup score (see table 1), as it is the most widely used clinical score, and its validity and reliability have been well demonstrated. However, RCTs included in the review use a variety of croup scores. Mild croup: occasional barking cough; no stridor at rest; and no to mild suprasternal, intercostal indrawing (retractions of the skin of the chest wall), or both corresponding to a Westley croup score of 0–2. Moderate croup: frequent barking cough, easily audible stridor at rest, and suprasternal and sternal wall retraction at rest, but no or little distress or agitation, corresponding to a Westley croup score of 3–5. Severe croup: frequent barking cough, prominent inspiratory and — occasionally — expiratory stridor, marked sternal wall retractions, decreased air entry on auscultation, and significant distress and agitation, corresponding to a Westley croup score of 6–11. Impending respiratory failure: barking cough (often not prominent), audible stridor at rest (can occasionally be hard to hear), sternal wall retractions (may not be marked), usually lethargic or decreased level of consciousness, and often dusky complexion without supplemental oxygen, corresponding to a Westley croup score of greater than 11. During severe respiratory distress, a young child's compliant chest wall "caves in" during inspiration, causing unsynchronised chest and abdominal wall expansion (paradoxical breathing). By this classification scheme, about 85% of children attending general emergency departments with croup symptoms have mild croup, and less than 1% have severe croup (unpublished prospective data obtained from 21 Alberta general emergency departments).

Table 1.

Clinical scores for assessing severity of croup.

Incidence/ Prevalence

Croup has an average annual incidence of 3%, and accounts for 5% of emergency admissions to hospital in children aged under 6 years in North America (unpublished population-based data from Calgary Health Region, Alberta, Canada, 1996–2000). One retrospective Belgian study found that 16% of children aged 5–8 years had suffered from croup at least once, and 5% had experienced recurrent croup (at least 3 episodes). We are not aware of epidemiological studies establishing the incidence of croup in other parts of the world.

Aetiology/ Risk factors

One long-term prospective cohort study suggested that croup occurred most commonly in children aged between 6 months and 3 years, but can also occur in children as young as 3 months and as old as 12–15 years. Case-report data suggest that it is extremely rare in adults. Infections occur predominantly in late autumn, but can occur during any season. Croup is caused by a variety of viral agents and, occasionally, by Mycoplasma pneumoniae. Parainfluenza accounts for 75% of all cases, with the most common type being parainfluenza type 1. Prospective cohort studies suggest that the remaining cases are mainly respiratory syncytial virus, metapneumovirus, influenza A and B, adenovirus, coronavirus, and mycoplasma. Viral invasion of the laryngeal mucosa leads to inflammation, hyperaemia, and oedema. This leads to narrowing of the subglottic region. Children compensate for this narrowing by breathing more quickly and deeply. In children with more severe illness, as the narrowing progresses, their increased effort at breathing becomes counter-productive, airflow through the upper airway becomes turbulent (stridor), their compliant chest wall begins to cave in during inspiration, resulting in paradoxical breathing, and consequently the child becomes fatigued. With these events — if untreated — the child becomes hypoxic and hypercapnoeic, which eventually results in respiratory failure and arrest.

Prognosis

Croup symptoms resolve in most children within 48 hours. However, a small percentage of children with croup have symptoms that persist for up to a week. Rates of hospital admission vary significantly between communities but, on average, less than 5% of all children with croup are admitted to hospital. Of those admitted to hospital, only 1%–3% are intubated. Mortality is low; in one 10-year study, less than 0.5% of intubated children died. Uncommon complications of croup include pneumonia, pulmonary oedema, and bacterial tracheitis.

Aims of intervention

To minimise the duration and severity of disease episodes, with minimal adverse effects.

Outcomes

Symptom severity: change in clinical severity over time (as measured by a range of clinical scores — e.g., the Westley croup score [see table 1]); change in upper airway obstruction (as measured by several pathophysiological measurement tools). Need for additional medical attention / admission to hospital: rate of return to healthcare practitioner after an episode; rate and duration of hospital admission. Adverse effects of treatment. For the question concerning children with impending respiratory failure because of severe croup: rate and duration of airway intubation; symptom severity; adverse effects of treatment.

Methods

Clinical Evidence search and appraisal June 2008. The following databases were used to identify studies for this systematic review: Medline 1966 to June 2008, Embase 1980 to June 2008, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2008, Issue 2 (1966 to date of issue). An additional search was carried out of the NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs, RCTs, and observational studies (cohort studies, case studies, and case reports) in any language. There was no minimum length of follow-up required to include studies. We did not exclude studies on the basis of loss to follow-up. We did not exclude RCTs described as "open", "open label", or not blinded. Studies on corticosteroids were required to have at least 20 participants, but for all other interventions we included studies of any size. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as RRs and ORs. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Croup.

Glossary

High-quality evidence

Further research is very unlikely to change our confidence in the estimate of effect.

Intermittent positive pressure breathing

A type of physiotherapy which involves assisted breathing with a pressure cycled ventilator triggered into inspiration by the user and allowing passive expiration. The user begins to inhale through the machine, which senses the breath and augments it by delivering gas to the user. When a preset pressure is reached, the machine stops delivering gas and allows the user to breathe out. In most devices, the inspiratory sensitivity, flow rate, and pressure can be varied to suit the user's needs, but some devices adjust the sensitivity and flow automatically. The aim is to increase lung volume, which is thought to cause a reduction in airways resistance and an improvement in ventilation.

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Moderate-quality evidence

Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Paradoxical breathing (thoracoabdominal asynchrony)

A form of breathing that occurs in young children with severe respiratory distress. Typically, in well people the abdomen and chest expand and contract in a synchronised fashion with respiration. Children compensate for narrowing of their upper airway by increasing their work of breathing, which increases intrapleural pressure and the rate of airflow through the upper airway. With greater increases in pleural pressure, during inspiration, a young child's compliant chest wall begins to collapse as the abdomen protrudes, owing to diaphragmatic contraction. This thoracoabdominal asynchrony is commonly referred to as paradoxical breathing. The severity of paradoxical breathing can be measured using a respiratory inductance plethysmograph, which measures the phase angle. A decrease in phase angle equates to a reduction in the severity of paradoxical breathing.

Very low-quality evidence

Any estimate of effect is very uncertain.

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

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BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

A single oral dose of dexamethasone improves symptoms in children with mild croup, compared with placebo.

We found no clinically important results from RCTs or observational studies comparing the effects of oral dexamethasone versus other corticosteroids, or comparing single-dose dexamethasone with multiple doses, in children with mild croup.

Benefits and harms

Oral dexamethasone versus placebo:

We found no systematic review, but found two RCTs.

Symptom severity

Oral dexamethasone compared with placebo A single dose of oral dexamethasone is more effective than placebo at reducing symptom severity in the first 24 hours in children with mild croup (moderate-quality evidence).

No data from the following reference on this outcome.

Need for additional medical attention / admission to hospital

Oral dexamethasone compared with placebo A single dose of oral dexamethasone is more effective than placebo at reducing the need for additional medical attention in children with mild croup (high-quality evidence).

Adverse effects

No data from the following reference on this outcome.

Single versus multiple doses of oral dexamethasone:

We found no systematic review or RCTs.

Corticosteroids other than dexamethasone:

We found no systematic review or RCTs.

Further information on studies

Oral dexamethasone versus placebo: The RCT reported that by 72 hours after treatment, differences between the dexamethasone and placebo groups in symptom severity were diminished, with complete symptom resolution in more than 75% of children in both groups (no further data reported).

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

Although oral decongestants are often used in children with mild to moderate croup, there is no evidence to support their use in clinical practice.

We found no direct information from RCTs or observational studies about oral decongestants in children with mild croup.

Benefits and harms

Oral decongestants versus placebo or other interventions:

We found no systematic review, RCTs, or observational studies of sufficient quality on oral decongestants in children with mild croup.

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

Although humidification is often used in children with mild to moderate croup, there is no evidence to support its use in clinical practice and current consensus suggests that it is ineffective.

We found no direct information from RCTs or observational studies about the effects of humidification in children with mild croup.

Benefits and harms

Humidification versus placebo or other interventions:

We found no systematic review, RCTs, or observational studies of sufficient quality evaluating the effects of humidification in children with mild croup.

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

There is consensus that antibiotics do not improve symptoms in croup of any severity, as croup is usually viral in origin.

We found no direct information from RCTs or observational studies about the effects of antibiotics in children with mild croup.

Benefits and harms

Antibiotics versus placebo or other interventions:

We found no systematic review, RCTs, or observational studies of sufficient quality evaluating antibiotics in children with mild croup (see comment).

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

In children with moderate to severe croup, nebulised budesonide reduces symptoms compared with placebo.

Oral dexamethasone is as effective as nebulised budesonide at reducing symptoms, and is less distressing for the child.

Adding nebulised budesonide to oral dexamethasone does not seem to improve efficacy compared with either drug alone.

Benefits and harms

Nebulised budesonide versus placebo:

We found one systematic review (search date 2003, 6 RCTs).] Although most of the studies included in the review were in children admitted to hospital for croup, it included one RCT (54 children) that included children with mild to moderate croup (hoarseness, inspiratory stridor, and barking cough; also, Westley score 2 or greater after breathing humidified oxygen for 15 minutes).

Symptom severity

Nebulised budesonide compared with placebo Nebulised budesonide is more effective than placebo at reducing symptom severity over 6 to 24 hours in children with moderate to severe croup (moderate-quality evidence).

Need for additional medical attention / admission to hospital

Nebulised budesonide compared with placebo Nebulised budesonide seems more effective than placebo at reducing the proportion of children requiring return hospital visits and readmissions in children with moderate to severe croup (moderate-quality evidence).

Adverse effects

No data from the following reference on this outcome.

Nebulised budesonide versus oral dexamethasone:

See option on dexamethasone (oral) versus nebulised budesonide.

Nebulised budesonide versus intramuscular dexamethasone:

See option on dexamethasone (intramuscular) versus nebulised budesonide.

Nebulised budesonide versus budesonide (nebulised) plus oral dexamethasone:

See option on dexamethasone (oral) plus budesonide (nebulised).

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

In children with moderate to severe croup, intramuscular or oral dexamethasone reduces symptoms compared with placebo.

Benefits and harms

Intramuscular or oral dexamethasone versus placebo:

We found one systematic review (search date 2003).

Symptom severity

Intramuscular or oral dexamethasone compared with placebo Oral or intramuscular dexamethasone seems no more effective at reducing symptom severity at 6 hours, but may be more effective at 12 to 24 hours, in children with moderate to severe croup (moderate-quality evidence).

Need for additional medical attention / admission to hospital

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

Three of the five RCTs (148 children) included in the meta-analysis were in children described as having moderate croup, while the other 2 RCTs (67 children) were in children admitted to hospital for croup, although the severity of croup in these children was not clearly described.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

Intramuscular dexamethasone may be more effective than nebulised budesonide at reducing symptoms in children with moderate to severe croup.

Benefits and harms

Intramuscular dexamethasone versus nebulised budesonide:

We found one systematic review (search date 2003), which identified two RCTs.

Symptom severity

Intramuscular dexamethasone compared with nebulised budesonide Intramuscular dexamethasone may be more effective than nebulised budesonide at reducing symptoms in children with moderate to severe croup (low-quality evidence).

Need for additional medical attention / admission to hospital

Intramuscular dexamethasone compared with nebulised budesonide We don't know how intramuscular dexamethasone and nebulised budesonide compare at reducing the need for admission to hospital (low-quality evidence).

Adverse effects

Further information on studies

In this RCT, children randomised to receive budesonide did not receive a placebo intramuscular injection, but had an elastic bandage placed on their thigh to aid in masking. Therefore, it is possible that masking may not have been maintained, potentially biasing the results of the study.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

Oral dexamethasone is as effective as nebulised budesonide at reducing symptoms, and is less distressing for the child.

Benefits and harms

Oral dexamethasone versus nebulised budesonide:

We found one systematic review (search date 2003), which identified two RCTs.

Symptom severity

Oral dexamethasone compared with nebulised budesonide Oral dexamethasone and nebulised budesonide are equally effective at reducing symptom severity in children with moderate to severe croup (moderate-quality evidence).

No data from the following reference on this outcome.

Need for additional medical attention / admission to hospital

Oral dexamethasone compared with nebulised budesonide Oral dexamethasone and nebulised budesonide are equally effective at reducing the need for admission to hospital (high-quality evidence).

Adverse effects

No data from the following reference on this outcome.

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

We don't know whether oral dexamethasone or oral prednisolone is more effective at reducing the need for further medical attention.

Benefits and harms

Oral dexamethasone versus oral prednisolone:

We found two RCTs.

Symptom severity

No data from the following reference on this outcome.

Need for additional medical attention / admission to hospital

Oral dexamethasone compared with oral prednisolone We don't know how oral dexamethasone and oral prednisolone compare at reducing the need for further medical attention (low-quality evidence).

Adverse effects

No data from the following reference on this outcome.

Further information on studies

Substantive changes

Dexamethasone (oral) versus prednisolone (oral) in children with moderate to severe croup One RCT added comparing prednisolone versus dexamethasone 0.6 mg/kg versus dexamethasone 0.15 mg/kg, all given orally. It found no significant difference among the groups in hospital admission or in the need for further medical attention. Categorisation changed (Unknown effectiveness).

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

We don't know whether intramuscular or oral dexamethasone is more effective at reducing the need for additional medical attention.

Benefits and harms

Intramuscular versus oral dexamethasone:

We found one systematic review (search date 2003, 2 RCTs).

Symptom severity

No data from the following reference on this outcome.

Need for additional medical attention / admission to hospital

Intramuscular dexamethasone compared with oral dexamethasone We don't know how intramuscular dexamethasone and oral dexamethasone compare at reducing the need for additional medical attention (low-quality evidence).

Adverse effects

No data from the following reference on this outcome.

Further information on studies

One of the RCTs (95 children) identified by the review included children with Westley scores of 2 or greater, and may therefore have included some children with mild to moderate croup. In both RCTs, those children randomised to receive oral dexamethasone did not receive a placebo intramuscular injection, but had a syringe hub pressed against their thigh. It is possible, therefore, that blinding may not have been maintained, potentially biasing the results of the study.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

A dexamethasone dose of 0.15 mg/kg may be as effective as a dose of 0.6 mg/kg.

Benefits and harms

Higher-dose dexamethasone versus lower-dose dexamethasone:

We found one systematic review (search date 2003) and two subsequent RCTs. The systematic review identified one RCT.

Symptom severity

Higher-dose dexamethasone compared with lower-dose dexamethasone Higher-dose (0.6 mg/kg) and lower-dose (0.3 mg/kg and 0.15 mg/kg) dexamethasone seem equally effective at improving symptom scores at 6 hours (moderate-quality evidence).

No data from the following reference on this outcome.

Need for additional medical attention / admission to hospital

Higher-dose dexamethasone compared with lower-dose dexamethasone We don't know whether higher- and lower-dose dexamethasone differ in effectiveness at reducing return visits or hospital admissions (low-quality evidence).

Adverse effects

No data from the following reference on this outcome.

Further information on studies

Substantive changes

Dexamethasone (oral), higher dose versus lower dose in children with moderate to severe croup One RCT added comparing dexamethasone 0.6 mg/kg versus dexamethasone 0.15 mg/kg versus prednisolone, all given orally. It found no significant difference among the groups in hospital admission or in the need for further medical attention. Condition re-structured: separated from Dexamethasone (im) v dexamethasone (oral). Categorisation unchanged (Unknown effectiveness).

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

Adding nebulised budesonide to oral dexamethasone does not seem to improve efficacy compared with either drug alone.

Benefits and harms

Oral dexamethasone plus nebulised budesonide versus nebulised budesonide alone:

We found one systematic review (search date 2003), which identified one RCT (see option on dexamethasone [oral] versus budesonide [nebulised]).

Symptom severity

Oral dexamethasone plus nebulised budesonide compared with nebulised budesonide alone Oral dexamethasone plus nebulised budesonide is no more effective than nebulised budesonide alone at reducing symptom severity at 4 hours in children with moderate to severe croup (moderate-quality evidence).

Need for additional medical attention / admission to hospital

Oral dexamethasone plus nebulised budesonide compared with nebulised budesonide alone We don't know whether oral dexamethasone plus nebulised budesonide is more effective than either drug alone at reducing hospital admission rates at 1 week in children with moderate to severe croup (low-quality evidence).

Adverse effects

Oral dexamethasone plus nebulised budesonide versus oral dexamethasone alone:

We found one systematic review (search date 2003), which identified one RCT (see option on dexamethasone [oral] versus budesonide [nebulised]), and one subsequent RCT.

Symptom severity

Oral dexamethasone plus nebulised budesonide compared with oral dexamethasone alone Oral dexamethasone plus nebulised budesonide is no more effective than oral dexamethasone alone at reducing symptom severity at 4 hours in children with moderate to severe croup (moderate-quality evidence).

No data from the following reference on this outcome.

Need for additional medical attention / admission to hospital

Oral dexamethasone plus nebulised budesonide compared with oral dexamethasone alone We don't know whether oral dexamethasone plus nebulised budesonide is more effective than either drug alone at reducing hospital admission rates at 1 week or duration in hospital stay in children with moderate to severe croup (low-quality evidence).

Adverse effects

No data from the following reference on this outcome.

Further information on studies

The RCT reported that one child developed oral thrush after treatment with budesonide; one child developed hives with dexamethasone; another child was reported to show violent behaviour after treatment with oral dexamethasone; and one child was reported to be more hyperactive than usual after treatment with both oral dexamethasone and nebulised budesonide.

Substantive changes

Dexamethasone (oral) plus budesonide (nebulised) versus either drug alone in children with moderate to severe croup No new RCTs added; evidence re-evaluated. One systematic review and one subsequent RCT found no significant difference in croup severity scores at 4 hours, or the proportion of children admitted to hospital, between combined treatment with dexamethasone and budesonide, and either treatment alone; thus, combining interventions confers no additional benefit. Categorisation for combination changed (Unlikely to be beneficial).

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

Oxygen is standard treatment in children with respiratory distress.

We found no direct information from RCTs or observational studies about the effects of oxygen in children with moderate to severe croup. There is widespread consensus that oxygen is beneficial in children with severe respiratory distress.

Benefits and harms

Oxygen versus no oxygen treatment:

We found no systematic review, RCTs, or observational studies of sufficient quality evaluating the effects of oxygen in children with moderate to severe croup. An RCT comparing oxygen versus no oxygen in children with severe croup would be considered unethical. We found one prospective cohort study, which showed that children with croup can have hypoxia, even in the absence of severe upper airway obstruction, apparently because of intrapulmonary shunting. This study did not attempt to find out if administration of oxygen decreases respiratory effort.

Oxygen versus heliox (helium–oxygen mixture):

See option on heliox (helium–oxygen mixture).

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

In children with moderate to severe croup, nebulised adrenaline (epinephrine) reduces symptoms compared with placebo.

Nebulised adrenaline given as three doses within 1 hour has been associated with MI.

Benefits and harms

Nebulised adrenaline (epinephrine) versus placebo or no treatment:

We found no systematic review but found three small RCTs. The RCTs reported no adverse effects, and in particular observed no increase in heart rate or respiratory rate with adrenaline (see adverse effects for details from one SR, search date 2004).

Symptom severity

Nebulised adrenaline (epinephrine) compared with placebo or no treatment Nebulised adrenaline (epinephrine) is more effective in the short term at reducing symptom severity at 10–30 minutes in children with moderate to severe croup (moderate-quality evidence).

Need for additional medical attention / admission to hospital

No data from the following reference on this outcome.

Adverse effects

Adrenaline, nebulised versus heliox (helium–oxygen mixture):

We found no systematic review but found one small RCT.

Symptom severity

Nebulised adrenaline (epinephrine) compared with heliox We don't know whether nebulised adrenaline plus oxygen is more effective than nebulised saline plus heliox at improving symptom severity over 4 hours in children with moderate to severe croup (very low-quality evidence).

Need for additional medical attention / admission to hospital

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

Adrenaline, nebulised versus heliox (helium-oxygen mixture) Children were treated with either one or two normal saline nebulisations, followed by the delivery of heliox (helium 70%–oxygen 30%) for 3 hours, or one or two racemic adrenaline nebulisations (2.25%, 0.5 mL), followed by the delivery of 100% oxygen for 3 hours, both delivered through a tightly fitting mask. The second nebulisation was ordered at the discretion of the attending physician, based on whether the child had continued respiratory distress.

Adrenaline (epinephrine), nebulised versus placebo or no treatment — adverse effects: In one of the RCTs (21 children with acute bronchiolitis) included in the review, pallor was reported in 47% of children treated with adrenaline compared with 14% treated with placebo (significance of difference between groups not reported). The RCTs reported no adverse effects, and in particular observed no increase in heart rate or respiratory rate with adrenaline.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

We don't know whether L-adrenaline or racemic adrenaline is more effective at reducing symptom severity in children with moderate to severe croup.

Benefits and harms

L-adrenaline versus racemic adrenaline (epinephrine):

We found no systematic review but found one small RCT. The RCT gave no comparative data on adverse effects, but observed no increase in heart rate or respiratory rate with adrenaline.

Symptom severity

L-adrenaline compared with racemic adrenaline We don't know how L-adrenaline and racemic adrenaline compare for at reducing symptom severity in children with moderate to severe croup (low-quality evidence).

Need for additional medical attention / admission to hospital

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

The RCT gave no information on adverse effects; in particular, it observed no increase in heart rate or respiratory rate with adrenaline.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

Nebulised adrenaline (epinephrine) has a short-term effect on symptoms of croup, but we don't know whether adding intermittent positive-pressure breathing (IPPB) to nebulised adrenaline further improves symptoms.

Benefits and harms

Nebulisation alone versus nebulisation plus intermittent positive pressure breathing (IPPB):

We found no systematic review but found one small, weak RCT. The RCT gave no comparative data on adverse effects, but observed no increase in heart rate or respiratory rate with adrenaline.

Symptom severity

Nebulised adrenaline plus intermittent positive pressure breathing (IPPB) compared with nebulised adrenaline alone Nebulised adrenaline plus IPPB may be no more effective than nebulised adrenaline alone at reducing symptom severity in children with moderate to severe croup (low-quality evidence).

Need for additional medical attention / admission to hospital

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

The RCT found that both methods of adrenaline delivery significantly reduced croup score from baseline at 30 and 60 minutes (P <0.01) but not at 90 or 120 minutes.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

We don't know whether short-acting nebulised beta 2 agonists are beneficial in children with moderate to severe croup as we found no studies.

Benefits and harms

Nebulised short-acting beta2 agonists versus placebo or other interventions:

We found no systematic review, RCTs, or observational studies of sufficient quality evaluating the effects of nebulised short-acting beta2 agonists in children with moderate to severe croup.

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

We don't know whether oral decongestants are beneficial in children with moderate to severe croup.

Benefits and harms

Oral decongestants versus placebo or other interventions:

We found no systematic review, RCTs, or observational studies of sufficient quality on oral decongestants in children with moderate to severe croup.

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

We don't know whether heliox (helium–oxygen mixture) is beneficial in children with moderate to severe croup.

Benefits and harms

Heliox (helium–oxygen mixture) versus oxygen alone:

We found one RCT comparing heliox (helium 70%–oxygen 30%) versus oxygen 30% alone.

Symptom severity

Heliox (helium–oxygen mixture) compared with oxygen alone We don't know how heliox and oxygen alone compare at reducing symptom severity in children with moderate to severe croup (low-quality evidence).

Need for additional medical attention / admission to hospital

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Heliox (helium–oxygen mixture) versus nebulised adrenaline (epinephrine):

See option on nebulised adrenaline (epinephrine).

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

We found no direct information from RCTs or observational studies about the effects of antibiotics in children with moderate to severe croup. There is consensus that antibiotics do not shorten the clinical course of a disease that is predominantly viral in origin. However, this does not apply if bacterial tracheitis is suspected.

Benefits and harms

Antibiotics versus placebo or other interventions:

We found no systematic review, RCTs, or observational studies of sufficient quality on antibiotics in children with moderate to severe croup.

Further information on studies

We found two case reports of children initially diagnosed with croup who were treated with both dexamethasone and antibiotics for several days. One child was later diagnosed as having herpetic tracheitis, and the other as having candida laryngotracheitis.

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

We don't know whether humidification is beneficial in children with moderate to severe croup.

Hot humidified air has been associated with scalds.

Benefits and harms

Humidified air versus non-humidified or low humidified air:

We found one systematic review (search date 2006) and one additional RCT.

Symptom severity

Humidified air compared with non-humidified or low-humidity air Humidified air is no more effective than non-humidified or low-humidity air at reducing symptom severity in children with moderate to severe croup at 30–60 minutes (moderate-quality evidence).

Need for additional medical attention / admission to hospital

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

In children with impending respiratory failure caused by severe croup, nebulised adrenaline (epinephrine) is considered likely to be beneficial.

Benefits and harms

Nebulised adrenaline (epinephrine) versus placebo or other interventions:

We found no systematic review, RCTs, or observational studies evaluating the effects of adrenaline (epinephrine) in children with impending respiratory failure due to severe croup. Such an RCT would be considered unethical. There is consensus that adrenaline is beneficial in children with impending respiratory failure due to severe croup (see comment). We found two cohort studies in children treated with adrenaline for acute upper airway obstruction (see comments).

Further information on studies

Substantive changes

Adrenaline (epinephrine), nebulised in children with impending respiratory failure due to severe croup No new evidence. RCTs in children with impending respiratory failure are unlikely to take place as they would be considered unethical. Most clinicians believe nebulised adrenaline to be effective, so categorisation changed to Likely to be beneficial by consensus.

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

Nasogastric prednisolone reduces the need for, or duration of, intubation.

Benefits and harms

Corticosteroids versus placebo:

We found one systematic review (search date 1987) and one subsequent RCT.

Need for intubation

Corticosteroids compared with placebo Corticosteroids (oral, intramuscular or subcutaneous) are more effective than placebo at reducing the need for intubation, the duration of intubation, and the need for re-intubation in children with severe croup (moderate-quality evidence).

Symptom severity

No data from the following reference on this outcome.

Adverse effects

No data from the following reference on this outcome.

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

In children with impending respiratory failure caused by severe croup, oxygen is standard treatment.

Benefits and harms

Oxygen versus placebo or other interventions:

We found no systematic review, RCTs, or observational studies of sufficient quality evaluating the effects of oxygen in children with impending respiratory failure due to severe croup. An RCT comparing oxygen versus no oxygen in children with severe croup would be considered unethical. There is consensus that oxygen is beneficial in children with severe respiratory distress.

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

We don't know whether heliox (helium–oxygen mixture) is beneficial in children with impending respiratory failure due to severe croup as we found no studies.

Benefits and harms

Heliox versus placebo or other interventions:

We found no systematic review, RCTs, or observational studies of sufficient quality evaluating the effects of heliox (helium–oxygen mixture) in children with impending respiratory failure due to severe croup.

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

We found no direct information from RCTs or observational studies about the effects of antibiotics in children with impending respiratory failure due to severe croup. There is strong consensus that antibiotics do not shorten the clinical course of a disease that is predominantly viral in origin. This does not apply if bacterial tracheitis is suspected.

Benefits and harms

Antibiotics versus placebo or other interventions:

We found no systematic review, RCTs, or observational studies of sufficient quality on antibiotics in children with impending respiratory failure due to severe croup.

Further information on studies

Substantive changes

No new evidence

BMJ Clin Evid. 2009 Mar 10;2009:0321.

Summary

Sedatives are unlikely to be beneficial; they may decrease respiratory effort without improving ventilation.

Benefits and harms

Sedatives versus placebo or other interventions:

We found no systematic review, RCTs, or observational studies evaluating the effects of sedatives in children with impending respiratory failure due to severe croup.

Further information on studies

Substantive changes

No new evidence