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Three Part Question

In [patients with an acute exacerbations of asthma] does [a trial of NIV along with conventional medical therapy] reduce [intubation rates and associated complications]?

Clinical Scenario

A 25 year old woman is brought to the Emergency Department with a 24 hour history of increasing shortness of breath not relieved by multiple use of her salbutamol inhaler. She has been asthmatic since childhood and has had previous admissions including one to ITU. On arrival she is alert, tachypnoeic with a saturation of 92% on oxygen and tachycardic with a systolic BP of 90mmHg. She is sitting upright on the trolley, speaking single words only. You have heard that non-invasive ventilation might be a valuable addition to standard treatment in this situation and wonder whether there is any evidence to support such an approach.

Search Strategy

EBM Reviews - Cochrane Central Register of Controlled Trials 3rd Quarter 2008,
Ovid MEDLINE(R) 1950 to September Week 3 2008, EMBASE 1980 to 2008 Week 39, CINAHL - Cumulative Index to Nursing & Allied Health Literature 1982 to September Week 4 2008, EBM Reviews - Cochrane Database of Systematic Reviews 3rd Quarter 2008 using multifile searching:

asthma.mp. AND (non-invasive ventilation.mp.or noninvasive ventilation.mp. or niv.mp. or bipap.mp. or cpap.mp. or ppniv.mp. or positive pressure.mp.) AND (emergency.mp. or acute.mp. or severe.mp. or life threatening.mp.) Limit to English language, human and records de-duped.

Search Outcome

282 papers found of which 9 were relevant and of sufficient quality to be included in this review.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Shivaram U et al 1993 USA	Adults Acute asthma CPAP (21 patients) v CPAP with no pressure support (6 patients)	RCT	RR and SOB	Decreased with CPAP (p<0.01)	Small sample size with much smaller control group ?CPAP with no pressure support would cause greater perceived dyspnoea Patients selected on absolute PEFR not % predicted therefore not real indicator of severity
Pollack CV et al 1995 USA	Adults Severe asthma 2 doses albuterol 20 minutes apart delivered by BIPAP or small volume nebuliser	Convenience RCT	PEFR	Increased with BIPAP (p=0.0011)	Convenience randomisation - patients only included if 1 of 2 principal investigators present No mention of how randomisation carried out Suggests BIPAP-driven nebs improve PEFR in acute asthma but no other conclusion re BIPAP in asthma can be drawn
			Sp02/HR/RR	No difference
Meduri GU et al 1996 USA	Adults Acute asthma refractory to medical management admitted to ICU BIPAP used to treat hypercapnic respiratory failure in 17 patients	Retrospective patient record review	RR/SOB	Decreased	Small sample size Not RCT ICU not ED setting - 2 patients required sedating to tolerate NIV - not common ED practice
			pH	Increased (p=0.0012)
			pC02	Decreased (p=0.002)
Fernandez MM et al 2001 Spain	Adults Status asthmaticus admittd to ICU and not responding to medical management ETT v NIV - 7 CPAP 15 BIPAP	Retrospective Observational Study	RR	Decreased with NIV	Small sample size Not RCT C02 lowest in medically managed, median in NIV and highest in ETT - ?treatment bias - ETT v NIV at discretion of attending physician ICU not ED setting NIV discontinued to give nebulisers
Holley MT et al 2001 USA	Adults Status asthmaticus Standard therapy (16) v BIPAP plus standard therapy (19)	RCT	Intubation rate	Increased in control group (not statistically significant)	Small sample size Study terminated early due to ethical concerns of participating physicians re 'witholding BIPAP' No blinding Suboptimal initial bronchodilator therapy
Soroksky A et al 2003 Israel	Adults Severe asthma BIPAP (17) v 'sham' BIPAP (16) (subtherapeutic pressures and holes cut in the tubing)	RCT	50% increase in FEV1	Greater in BIPAP group (p,0.004)	Small sample size NIV stopped to give nebs Mouth breathing allowed in control group threfore introducing physiological differences between groups No comparison with standard therapy alone ie no evidence that ''sham'' BIPAP not worse for patients than nebulisers alone
			RR	Decreased with BIPAP (p=0.02)
			Hospitalisation	3/17 BIPAP, 10/16 control (p=0.0134)
Carroll CL, Schramm CM 2006 USA	Children Status asthmaticus 5/79 children admitted to ICU with asthma during study period were treated with BIPAP	Retrospective Review	RR	Decreased (p=0.03)	5 case reports only Chart review not RCT 4/5 children treated with BIPAP were morbidly obese therefore introducing the possibility that BIPAP was effective for another cause of respiratory failure eg upper airway restriction/restrictive lung disease
Beers SL et al 2007 USA	Children Status asthmaticus refractory to conventional medical therapy (83 patients)	Retrospective chart review	RR	Decreased with BIPAP in 77%	Retrospective chart review not RCT No statistics No control group
			Sp02	Increased with BIPAP in 88%
Soma T et al, 2007, Japan	Adults with mild to moderate acute asthma all given steroids Control (14) vs high pressure NIPV (16) vs low pressure NIPV (14)	RCT	Change in FEV1 over 90 minutes	Significantly higher in high pressure NIPV vs control	Mild to moderate asthma only

Comment(s)

While there are quite a lot of papers that address the question there are only 3 completed RCTs and all these have relatively small numbers. One convenience-randomised study suggests improved benefits of nebulised albuterol driven by BIPAP. The published evidence is strong enough to suggest that a well designed RCT to determine whether NIPV is effective in the treatment of acute exacerbations of asthma should be carried out.

Clinical Bottom Line

The current published evidence does not support the routine use of NIPV in acute asthma.

References

1. Shivaram U et al Cardiopulmonary responses to Continuous Positive Airway Pressure in acute asthma Journ Crit Care 1993; 8(2): 87-92
2. Pollack CV et al Treatment of acute bronchospasm with B-adrenergic agonist aerosols delivered by a nasal Bilevel Positive Airway Pressure circuit Ann Emerg Med 1995; 26(5): 552-557
3. Meduri GU et al Noninvasive Positive Pressure Ventilation in Status asthmaticus Chest 1996; 110: 767-774
4. Fernandez MM et al Non-invasive Mechanical Ventilation in Status Asthmaticus Intensive Care Med 2001; 27: 486-492
5. Holley MT et al Ethical Dilemmas in a Randomised Trial of asthma treatment: Can Bayesian statistical analysis explain the results? Acad Emerg Med 2001; 8 (12)
6. Soroksky A et al A pilot Prospective, Randomised, Placebo-controlled trial of Bilevel Positive Airway Pressure in acute asthma attack Chest 2003; 123: 1018-1025
7. Carroll CL, Schramm CM Noninvasive Positive Pressure Ventilation for the treatment of status asthmaticus in children Ann Allergy Asthma Immunol 2006; 96: 454-459
8. Beers SL et al Bilevel Positive Airway Pressure in the treatment of status asthmaticus in pediatrics Am Journ Emerg Med 2007; 25: 6-9
9. Soma T, Hino M, Kida K et al. A Prospective and Randomized Study for Improvement of Acute Asthma by Non-invasive Positive Pressure ventilation (NIPV). Inter Med 2007;47:493-501.