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Three Part Question

Does [noninvasive positive-pressure ventilation (NPPV)] [in immunocompromised adults with acute respiratory failure] reduce [intubation rate or mortality]?

Clinical Scenario

A neutropenic 35-year-old man, who received chemotherapy five days ago for a Non-Hodgkin Lymphoma (NHL), presents to the emergency department with a febrile acute respiratory failure secondary to a pneumonia. The patient is hemodynamically stable, but shows a slow deterioration in his respiratory status. He now needs a FiO2 of 80% to keep his saturation over 92%. He should be transferred to the ICU in the next hour. The physician wonders whether NPPV might prevent intubation and therefore improve outcome in this immunocompromised host.

Search Strategy

No best bet on this topic was found.
- Ovid MEDLINE(R) (1950 to September week 1 2010): 97 articles
- EMBASE (1950 to September week 1 2010 via Elsevier): 203 articles
- Cochrane library (to September week 1 2010): 0 article

Medline search :
((non-invasive positive-pressure ventilation) OR (non invasive positive pressure ventilation) OR (non invasive positive pressure ventilation) OR (positive pressure non invasive ventilation) OR (ventilation, non invasive positive pressure) OR (non invasive ventilation) OR (non invasive ventilation, positive-pressure) OR (positive pressure ventilation, non invasive) OR (positive pressure non invasive ventilation) OR (ventilations, non invasive positive pressure) OR (ventilation, positive pressure non invasive) OR (non invasive ventilation, positive pressure) OR (continuous positive airway pressure) OR (intermittent positive-pressure breathing) OR (intermittent positive-pressure ventilation) OR (positive-pressure respiration))
AND
((respiratory insufficiency) OR (respiratory failure) OR (pneumonia) OR (respiratory distress syndrome) OR (hypoxemia) OR (hypercapnia))
AND
((immunocompromised) OR (immunosuppressed) OR (immunosuppression) OR (immunodeficiency) OR (immunologic deficiency) OR (acquired immunodefiency syndrome) OR (HIV) OR (neutropenia) OR (lymphocyte depletion) OR (hematologic neoplasms))

Embase search :
((intermittent positive pressure ventilation) OR (positive end expiratory pressure))
AND
((respiratory failure) OR (acute respiratory failure) OR (pneumonia) OR (adult respiratory distress syndrome) OR (noncardiogenic lung edema) OR (hypoxemia) OR (hypercapnia))
AND
((immunocompromised patient) OR (immunosuppression) OR (immune deficiency) OR (acquired immune deficiency syndrome) OR (Human immunodeficiency virus) OR (neutropenia) OR (lymphocyte depletion) OR (T cell depletion))

Cochrane library search:
((Positive-Presure Respiration) OR (Continuous Positive Airway Pressure) OR (Intermittent Positive-Pressure Breathing) OR (Intermittent Positive-Pressure Ventilation))
AND
((Respiratory Insufficiency) OR (Pneumonia) OR (Adult Respiratory Distress Syndrome) OR (hypoxemia) OR (hypercapnia)
AND
((Immunocompromised host) OR (immunosuppression) OR (Acquired Immunodeficiency Syndrome) OR (HIV) OR (Neutropenia) OR (lymphopenia))

Search Outcome

Inclusion criteria:
- Population: Immunocompromised adults with acute respiratory failure
- Intervention: NPPV
- Methodology: Meta-analysis, systematic reviews, RCT
- Outcomes: Intubation and/or mortality

Exclusion criteria: COPD, cardiogenic pulmonary edema, asthma, pediatrics, neonates, animal subjects, prehospital setting, post-extubation NPPV, post-operative care

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Antonelli, Conti, Bufi, Costa, Lappa, Rocco, Gasparetto & Meduri 2000 Italy	40 patients (20 with NPPV and 20 with standard treatment delivered by oxygen mask) who underwent solid organ transplantation and developed respiratory failure from December 1995 to October 1997 at a 14-bed, general intensive care unit of a university hospital	Prospective non-blinded randomized trial	Need for endotracheal intubation and mechanical ventilation	Significant reduction in the rate of endotracheal indubation in the NPPV group (20% vs 70%, p=0,002)	- Patients who had more than two organ failure were excluded. - 8 patients refused to participate. - No description of other relevant comorbidities like COPD. - 10 orotracheal and 8 nasotracheal intubation with unknown distribution in between the two groups. - 5 patients failed the standard therapy because they had pulmonary edema and did not received NPPV. That can overestimate the rate of endotracheal intubation in the standard treatment group. - Confidence interval not given.
			Complications not present at admission	Trend in reduction rate of fatal sepsis (20% vs 50%, p=0,05)
			Length of ICU and hospital stay	Significant reduction in length of stay in ICU for the survivors (5,5 vs 9 days, p=0,03)
			ICU and hospital mortality	Trend in reduction of ICU mortality (20% vs 50%, OR 4, 95%CI, 0,8-20, p=0,05) but hospital mortality did not differ
Hilbert, Gruson, Vargas, Valentino, Gbikipi-Benissan, Dupon, Reiffers & Cardinaud 2001 France	52 immunosupressed patients with respiratory failure, fever and pulmonary infiltrates (26 patients received intermittent NPPV and 26 standard treatment) consecutively enrolled from May 1998 through December 1999 in a 16-bed intensive care unit.	Prospective non-blinded randomized trial	Need for endotracheal intubation and mechanical ventilation	Significantly less intubation in the NPPV group in ICU (46% vs 77%, RR 0,60, 95% CI 0,38-0,96, p=0,03)	- No description of other relevant comorbidities. - NPPV group had a higher PaO2/FiO2 (141+/-24) than the standard treatment group (136+/-23). - Most of the benefit was observed with patients who were immunosuppressed from hematologic cancer and neutropenia (subgroups defined a priori) - 4 HIV patients enrolled, so no conclusions can be drawn for this subgroup.
			Complications not present at admission	Significantly less complications causing death in the ICU (38% vs 69%, p=0,03)
			ICU and hospital mortality	Significantly lower rate of death in the NPPV group compare with the standard treatment group in ICU (38% vs 69%, RR 0,56, 95%CI 0,32-0,96, p=0,03)

Comment(s)

Population: The use of NVVP was studied in organ transplant patients and other immunosuppressed hosts (neutropenia with ANC of less than 1000 after chemotherapy or bone marrow transplantation in patients with hematologic cancers, drug-induced immunosuppression or cytotoxic therapy for a non-malignant disease). Four acquired immunodeficiency syndrome patients were included in the Hilbert study, but no conclusion can be drawn for this small subgroup. In the Antonelli study, considering that more than 50% of the patients had hepatic transplantation, the observed benefit may be more for that specific intervention. In the Hilbert study, considering that more than 50% of the patients were immunosupressed from hematologic cancer and neutropenia, the observed benefit seems to be more for that subgroup that was defined a priori. Intervention: Both studies could not be blinded. Also, there was no description of use of potential other intervention to prevent for ventilator-associated pneumonias (mouth wash, use of endotracheal tubes with aspiration of subglottic secretions device) and no specific adjustments were made in the ventilatory settings for ARDS patients. If the mortality decreases in this population, the benefit may decrease for that outcome. However, it would not have an impact on the intubation rate. Comparaison: In the Hilbert study, although the authors mentioned those interventions were the same in both groups, no specification was outlined for sedation and ventilatory settings. Outcomes: The abovementionned results were obtained in non-blinded single centre randomized trials done in university level teaching hospitals in Italy and France. Further studies are needed in order to explore the external validity of those results, specifically in more actual settings using known interventions for nosocomial infections prevention (as ventilator-associated pneumonias) and ARDS ventilatory settings.

Clinical Bottom Line

NPPV for organ transplanted patients (mainly hepatic transplant) in acute respiratory failure or for immunosuppressed (hematologic cancer and neutropenia) patients with acute respiratory failure, pulmonary infiltrates and fever may reduce the rate of intubation and ICU mortality. Level of evidence 2b (Oxford Center for Evidence-based Medicine levels of Evidence) Grade of recommendation B : consistent level 2 or 3 studies

References

1. Antonelli, Conti, Bufi, Costa, Lappa, Rocco, Gasparetto & Meduri Noninvasive Ventilation for Treatment of Acute Respiratory Failure in Patients Undergoing Solid Organ Transplantation : A Randomized Trial JAMA 2000, Volume 283, Issue 2, p.235-241
2. Hilbert, Gruson, Vargas, Valentino, Gbikipi-Benissan, Dupon, Reiffers & Cardinaud Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates New England Journal of Medicine Volume 344, Numero 7, February 15th, 2001, p.481-487.