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Three Part Question

In [adults with acute respiratory failure and hypercapnic coma] does [non-invasive ventilation]lead to [lower mortality]?

Clinical Scenario

A 78-year-old female with long standing heart failure (New York Heart Association grade 3) is brought to the Emergency Department (ED) with respiratory distress and reduced conscious level. Arterial blood gas analysis demonstrates that the patient has type 2 respiratory failure and she scores 5/15 on the Glasgow Coma Scale (GCS). An opinion is sought from the Intensive Care Unit (ICU) physicians regarding the prospect of invasive mechanical ventilation (IMV), but they decide that the patient is not suitable for IMV. You consider instituting non-invasive ventilation (NIV). However, a depressed level of consciousness is traditionally thought to be a contraindication to NIV. This makes you wonder whether it would be an appropriate management strategy in this situation.

Search Strategy

Medline 1950–2010 May Week 4 and EMBASE 1980–2010 Week 22, via the Ovid interface
(??conscious$.mp. OR GCS.mp. OR coma.mp. OR exp Coma/OR exp Glasgow Coma Scale/) AND (exp Continuous Positive Airway Pressure/OR exp Ventilators, Mechanical/OR exp Positive-Pressure Respiration/OR exp Intermittent Positive-Pressure Ventilation/OR “BIPAP”.mp. OR (bi?level positive airway? pressure).mp. OR “NIPPV”.mp. OR “NIV”.mp. OR “NIMV”.mp. OR “CPAP”.mp. OR “continuous positive airway pressure”.mp.) AND (exp Hypercapnia/OR hypercapn$.mp. OR “type 2”.mp. OR “type II”.mp.) limit to human and English language.

The Cochrane Library, searched May 2010.

(Coma OR GCS OR Glasgow Coma Scale OR unconscious*) AND (non-invasive ventilation OR NIV OR BIPAP OR CPAP OR NIPPV).

Search Outcome

One hundred and ninety-four papers were found in Medline, 254 in EMBASE and 14 in the Cochrane Library, nine of which were relevant to the three-part question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Adent et al, 2001, France	One 92-year-old women, exacerbation of long standing CCF and COPD. GCS 3, pH 7.06, pCO2 185 mmHg Given BiPAP via facial mask for 10 h	Case report	Successful recovery of patient	GCS 15 and normalized ABG after 10 hours of BIPAP. Successfully discharged from hospital after 15 days	Single case study
Diaz et al, 2005, Spain	Patients with acute respiratory failure started on NIV in ICU, 95 with hypercapnic coma (10 with CCF), 863 not in coma (203 with CCF)	Prospective obsevational study	Successful treatment, failure of treatment, mortality	80% of comatosed patients improved with NIV, 13.7% required intubation, No significant difference between mortality of coma and non-coma groups	No comparison of NIV verses IMV in hypercapnic coma
Zhu et al, 2007, China	43 COPD patients with hypercapnic respiratory failure, 22 with GCS<10 and 21 GCS>10	Prospective case-control study	Success, failure, complications	No statistically significant difference between the 2 groups in any of the outcomes.	No comparison of NIV verses IMV in hypercapnic coma; small numbers
Briones et al, 2008, Ecuador	24 COPD patients with hypercapnic respiratory failure and GCS<8, 12 had NIV and 12 IMV	Prospective interventional case-control study	Hospital mortality, days of ventilation, 6 month survival	NIV had significantly lower hospital mortality and shorter time spent on ventilation. 6 month survival was not significantly different.	Poor blinding in selection into two groups, small numbers
Scala et al, 1997, Italy [Abstr]	74-year-old COPD patient on home oxygen, Presenting with hypercapnic coma (GCS 7)	Case report	Successful recovery	GCS 15 and normalised ABGs within 61 h of NIV	Single case (English abstract and very basic translation used)
Duenas-Pareja et al, 2002, Spain [Abstr]	13 patients with hypercapnic coma (GCS≤7), 10 COPD and three CCF. All treated with NIV	Cohort study	Successful recovery, mortality	9/13 recovered. 7/9 of those that recovered had their GCS and ABGs normalised within 48 h	Small study, no control group no comparison to IMV (English abstract and very basic translation used)
Scarpazza et al, 2008, Italy	62 patients with hypercapnic respiratory failure and ‘Do Not Intubate’ orders treated with NIV	Observational cohort study	Successful recovery	Indicated that patients with a depressed GCS performed significantly worse.	It is impossible to separate the effects of severity of illness and reduced GCS on the likelihood of recovery
Benhamou et al, 1992, France	30 patients with hypercapnic respiratory failure and varying conscious levels	Observational cohort study	Successful weaning from NIV, mortality	No significant difference in the parameters of successful and failure groups. ‘Coma’ patients performed favourably; however, ‘agitated’ patients appeared to perform worse than other groups	Use of nasal masks to deliver NIV. Formal GCS not stated. Only three ‘coma’ patients studied
Scala et al, 2005, Italy	80 COPD patients with hypercapnic respiratory failure. Divided into four groups of 20 patients depending on conscious level	Observational case–control Study	Successful recovery, mortality, complications	The GCS<8 group showed significantly higher mortality, no increase in complications It was reported that in those that recovered in the GCS<8 group their GCS rose quickly with NIV	Severity of illness was not adequately matched No comparison with IMV

Comment(s)

All nine of the papers identified suggest that NIV may be useful in hypercapnic coma. Of these nine studies, three presented comparisons of the use of NIV in patients with hypercapnic coma versus those without coma. Two papers demonstrated that there was no significant difference in outcome, or complication rate between coma and non-coma patients, one, however, did show that coma patients performed significantly worse. Only one study compared outcome of NIV and IMV in hypercapnic coma. This paper demonstrated that treatment with NIV conferred a significant survival advantage and reduced the time on ventilation. However, this study was small and not randomised.

Many of the studies also report that patients who were successfully treated with NIV showed a significant improvement in GCS and arterial blood gas (ABG) parameters in the first few hours of treatment. The other predictors of success were initial severity scores, although initial GCS and ABGs were not predictive of success.

Although there are few high-quality data on this subject (and more is always welcome), conclusions can be drawn. There seems to be a consensus that in an older population of coma patients due to hypercapnic respiratory failure, a trial of NIV can be recommended. Techniques to minimise the risk of gastric aspiration, such as maintaining the patient in an upright position and gradually titrating inspiratory positive airways pressure (IPAP) up from a low starting point (such as 10–12 cmH2O), would be prudent in this population.

Editor Comment

ABG, arterial blood gas; BiPAP, bilevel positive airways pressure; CCF, congestive cardiac failure; COPD, chronic obstructive pulmonary disease; GCS, Glasgow Coma Scale; NIV, non-invasive ventilation.

Clinical Bottom Line

Although high-quality data are lacking, NIV appears to be safe and effective in patients with hypercapnic coma and respiratory failure. Given the available evidence, when IMV is felt to be inappropriate, a trial of NIV is worthy of consideration.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.

References

1. Adent F, Racine SX, Lapostolle F et al. Full reversal of hypercapnic coma by noninvasive positive pressure ventilation. American journal of emergency medicine 2001:19(3);244-6
2. Diaz GG, Alcaraz AC, Talavera JCP et al. Noninvasive positive-pressure ventilation to treat hypercapnic coma secondary to respiratory failure. Chest 2005:127;952-60.
3. Zhu GF, Zhang W, Zong H et al. Effectiveness and safety of noninvasive positive-pressure ventilation for severe hypercapnic encephalopathy due to acute exacerbation of chronic obstructive pulmonary disease. Chinese Medical Journal 2007; 120(24): 2204-9.
4. Briones Claudett K, Briones Claudett M, Chung Sang Wong M et al. Noninvasive mechanical ventilation in patients with chronic obstructive pulmonary disease and severe hypercapnic neurological deterioration in the emergency room. European Journal of Emergency Medicine 2008:15(3);127-33.
5. Scala R, Archinucci I, Donato Alessi S, et al. La ventilazione non invasiva per nasale in un caso di coma ipercapnico. Minerva Anestesiol 1997;63:245–8.
6. Duenas-Pareja Y, Lopez-Martin S, Garcia-Garcia J, et al. Ventilacion no invasiva en pacientes con encefalopatia hipercapnica grave en una sala de hospitalizacion convencional. Arch Bronconeumol 2002;38:372–5.
7. Scarpazza P, Incorvaia C, di Franco G, et al. Effect of noninvasive mechanical ventilation in elderly patients with hypercapnic acute-on-chronic respiratory failure and a do-not-intubate order. Int J Chron Obstruct Pulmon Dis 2008;3:797–801.
8. Benhamou D, Girault C, Faure C, et al. Nasal mask ventilation in acute respiratory failure. Experience in elderly patients. Chest 1992;102:912–17.
9. Scala R, Naidi M, Archinucci I, et al. Noninvasive positive pressure ventilation in patients with acute exacerbations of COPD and varying levels of consciousness. Chest 2005;128:1657–66.