Non-invasive assisted ventilation (NIPPV/NIAV) in the management of acute hypercapnic failure secondary to COPD

Dr Vince Mak, Consultant Physician

Department of Respiratory and Critical Care Medicine,
Central Middlesex Hospital, Park Royal,


Fig.1. The Thinker. (A.Rodin)


The following article is a distillation of many years of personal experience with non-invasive ventilation techniques. Central Middlesex Hospital now has one of the most comprehensive acute non-invasive assisted ventilation services available in the UK, attracting a lot of trainees. The views expressed, although entirely personal, are based on evidence as much as possible. Some personal preferences to certain techniques will undoubtedly come through, but these will be highlighted that they are personal and not evidence based. Please do not take this article as gospel and do not think that these techniques are standard nor widely available in all hospitals, although all units who treat patients with acute COPD should aspire to provide this level of service.



Clinical Scenario

Mr PT is a 70yr old gentleman with a long history of severe COPD. He has smoked most of his life and has totalled around 80 pack years, but has stopped 3 months ago. His normal exercise tolerance is approximately 50 yards (m) at his own pace and less than one flight of stairs. He has had 2 admissions to hospital for acute infective exacerbations of his COPD within the last 12 months. Although hypoxic during acute exacerbations, he has never been in acute hypercapnic respiratory failure, and has not been hypoxic enough when reviewed in outpatients to fulfil the criteria for long term oxygen therapy. His FEV1 is 0.8l at best, FVC is 2.5l. He has no significant comorbidity and no history of occupational industrial exposure. He lives with his wife and they are independent in their daily activities.

You admit Mr PT from the A&E department (ER) with yet another acute infective exacerbation of his COPD. He has been getting increasingly short of breath over the last few days with a cough productive of purulent green sputum. He can only walk a few yards now and is short of breath on minimal exertion.

On examination, Mr PT is cyanosed breathing room air, barely able to complete his sentences. He is dehydrated and pyrexial 37.9°C but cardiovascularly stable but his pulse is 110/min. There is no peripheral oedema. His respiratory rate is 30 with prolonged expiration and pursed lip breathing. He is using his accessory muscles of respiration. His chest is grossly hyperexpanded with hyperresonance to percussion and reduced breath sounds but prolonged expiratory wheeze. There are no focal signs of infection. There is nothing else of significance to find on examination.

Investigations reveal slighlty raised white count with a neutrophilia, mildly elevated urea but normal creatinine. Electrolytes and liver function are normal. ECG is normal.. CXR shows gross hyperinflation but no evidence of consolidation. Sputum gram stain show gram negative bacilli. Arterial blood gases Taken breathing air:

You treat him with nebulised salbutamol (5mg) and Ipratropium bromide (500mcg) and controlled oxygen at 24%. In addition , you give an intravenous cephalosporin and hydrocortisone 100mg. 15 minutes later, he is no better and you give a second dose of nebulsied salbutamol and ipratropium. A further 15 minutes later, he is obviosuly beginning to tire and repeat blood gases on 24% O2 show:

His wife is begging you to do something. What are your treatment options?

  1. More nebulisers and increase the O2 concentration?
  2. Intubate and ventilate?
  3. Diamorphine
  4. Doxapram
  5. Non-invasive assisted ventilation.


NIAV and NIPPV are almost synominous except where NIPPV is used to mean specifically nasal intermittent positive pressure ventilation. Although NIPPV is the most widely used abbreviation, we shall use NIAV to avoid confusion.

Background and Theory

For those of you who are regularly involved the acute medical emergencies, the above scenario is all too common. Acute exacerbations of COPD accounts for a significant number of acute medical admissions to hospital (nearly 25% of acute medical beds in winter). The decision making never gets any easier, and now becomes even harder with the increasing availability of non-invasive assisted ventilation (NIAV). Before the advent of NIAV, there were only really 3 options; intubate and ventilate, doxapram or diamorphine.

Even with these 3 treatment options, the mortality from acute type II respiratory secondary to COPD is very high (6-34%). The most reliable predictors of mortality are age and degree of respiratory acidosis (i.e. severity of respiratory decompensation). pH > 7.26, mortality = 7%, pH < 7.26, mortality = 26% ( Jeffrey AA. Warren PM. Flenley DC. Acute hypercapnic respiratory failure in patients with chronic obstructive lung disease: risk factors and use of guidelines for management. Thorax. 1992; 47(1):34-40). However, recent studies have shown that NIAV in this scenario to be highly effective in the management of acute hypercapnic respiratory failure.

Theory behind NIAV

Hypercapnia in acute hypercapnic respiratory failure (AHRF) is due to ventilatory failure secondary to several factors:

  1. Exhaustion of the respiratory muscles
  2. Inadequate tidal volumes because of expiratory airflow obstruction and hyperinflation secondary to gas trapping increasing FRC.
  3. Reduced central drive to breath
  4. Plugging of airways with mucus and secretions
  5. Loss of "hypoxic drive" (the existence of this is currently in much debate).

NIAV may be beneficial in AHRF for several reasons:

  1. Respiratory muscles may be rested by augmentation of each breath by inspiratory pressure or volume support.
  2. Tidal volumes may be augmented by pressure or volume support.
  3. Expiratory airflow may be improved by applying a degree of positive expiratory pressure reducing dynamic airways compression and reducing hyperinflation.
  4. Timed breaths will compensate for lack of central drive.
  5. Higher levels of FiO2 can be given without fear of excessive respiratory depression.

Previous attempts at Noninvasive Assisted Ventilation for COPD

Noninvasive negative pressure ventilation

Non-invasive negative pressure ventilation has been available for many years for the management of chronic respiratory failure secondary to musculoskeletal disorders ( e.g. Cuirass ventilator, Pneumosuit, Tank ventilator and Hayek Oscillator), and have been very effective. However, since the availability of positve pressure techniques, the popularity of negative pressure devices has waned (especially in the UK).

This may be due to poor tolerance of techniques, especially at night compared with positive pressure devices, and there is a theoretical ncreased risk of inducing upper airways obstruction during sleep (i.e. actually producing sleep apnoea). There are problems with patient comfort and cumbersome equipment, and there is no facility to apply PEEP if necessary. There has been limited success with negative pressure devices in the management of chronic hypercapnic respiratory failure secondary to COPD, but no trials have been conducted in AHRF secondary to COPD.

Pluto LA, Fahey PJ, Sorenson L, Chandrasekhar AJ. Effect of 8 weeks of intermittent negative pressure ventilation on exercise parameters in patients with severe chronic obstructive lung disease. Am Rev Respir Dis 1985; 131:A64.

Cropp A, Dimarco AF. Effects of intermittent negative pressure ventilation on respiratory muscle function in patients with severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1987; 135:1056-1061.

Zibrak JD, Hill NS, Federman EC, Kwa SL, O'Donnell C. Evaluation of intermittent long-term negative-pressure ventilation in patients with severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1988; 138:1515-1518

Celli B, Lee H, Criner G, et al. Controlled trial of external negative pressure ventilation in patients with severe chronic airflow obstruction. Am Rev Respir Dis 1989; 140:1251-1256.

Cooper CB, Harris ND, Howard P. Acute effects of external negative pressure ventilation in chronic obstructive pulmonary disease compared with normal subjects. Eur Resp J 1991; 4:63-68.

NIAV in Chronic Hypercapnic Respiratory Failure

Non-invasive positive pressure/volume devices have been a relatively recent development with equipment evolving from ICU ventilator technology and nasal CPAP ventilators for sleep apnoea. Prior manifestations of NIAV include Mouth Intermittent Positive Pressure Breathing (IPPB) e.g Bird. Initial studies were performed in chronic respiratory failure secondary to neuromuscular disease or chest wall deformity with impressive results. So impressive that many chronic respiratory care units have now discarded their tank and cuirass ventilators in favour of NIAV.

Several papers have investigated the use of NIAV is the management of CHRF secondary to severe COPD. The results have been favourable but not dramatic, and patient compliance and acceptability can be a problem. Currently, there is a large European study ongoing, comparing long term oxygen therapy with NIAV +/- oxygen.

Bach JR, ALba A, Mosher R, Delaubier A. Intermittent positive pressure ventilation via nasal access in the management of respiratory insufficiency. Chest 1987; 92: 168-170.

One of the first descriptions of the application of NIAV in patients with acute on chronic respiratory failure who were previously dependent on IPPB.

Carrey Z, Gottfried SB. Ventilatory muscle support in respiratory failure with nasal positive pressure ventilation. Chest 1990; 97: 150-158.

Elliott MW, Mulvey DA, Moxham J, et al. Domiciliary nocturnal nasal intermittent positive pressure ventilation in COPD: mechanisms underlying changes in arterial blood gas tensions. Eur Resp J. 1991; 4: 1044-1052.

Petrof BJ, Kimoff RJ, Levy RD, et al. Nasal conitinuous positive airway pressure facilitates respiratory mucle function during sleep in severe chronic obstructive pulmonary disease. Am Rev Respir Dis. 1991; 143: 928-935.

Elliott MW, Simonds AK, Carroll MP, et al. Domiciliary nocturnal nasal intermittent positive pressure ventilation in hypercapnic respiratory failure due to chronic obstructive lung disease: effects on sleep and quality of life. Thorax. 1992;47: 342-348.

Leger P, Bedicam JM, Cornete A. et al. Nasal intermittent positive pressure ventilation. Long term follow-up in patients with severe chronic respiratory insufficiency. Chest 1994; 105: 100-105.

Simonds AK, Elliott MW. Outcome of domiciliary nasal intermittent positive pressure vnetilation in restrictive and obstructive disorders. Thorax 1995; 50: 604-609.

NIAV in Acute Respiratory Failure - Seminal Papers

There have now bee many studies of NIPPV/NIAV in COPD. The following are a selection some of the most important papers, both for and against the use of NIAV in AHRF secondary to COPD. I apologise in advance to any authors who I have left out, but if you feel that your paper should be included in this review, then please write to me and let me know why.

NIAV in Acute Respiratory failure : Early Studies

Meduri GU. Conoscenti CC. Menashe MD. Nair S. Noninvasive face mask ventilation in patients with acute respiratory failure. Chest. 95: 865-870, 1989.

Meduri GU. Abou-Shala N. Fox RC. Jones CB. Leeper KV. Wunderink RG. Noninvasive face mask mechanical ventilation in patients with acute hypercapnic respiratory failure. Chest. 100(2):445-54, 1991.

10 patients with a variety of lung conditions (but only 6 hypercapnic) ventilated via face mask with pressure support. All improved in gas exchange and ventilation and tolerated technique well but 3 required intubation and formal ventilation.

Brochard L, Isabey D, Piquet J, et al. Reversal of acute exacerbations of chronic obstructive lung disease by inspiratory assistance with a face mask. NEJM 1990; 323: 1523-30

First to look specifically at AHRF secondary to COPD. Laboratory and clinical study compared with historical controls. They used pressure support ventilation via a full face mask. Most patients showed rapid improvements (after 45 minutes) in:

Only 1/13 patients required intubation compared with 11/13 controls. Treated patients required shorter periods of ventilatory support and no need for ICU level of care.

Elliott MW, Steven MH, Phillips GD, Branthwaite MA. Noninvasive mechanical ventilation in patients with acute respiratory failure. Br Med J 1990;300: 358-60

6 patients with various causes of acute on chronic hypercapnic respiratory failure. They used NIPPV via a nasal mask and found improvements in:

2 patients died but only 1 in the acute phase.

Meduri GU, Abou-ShalaN, Fox RC, et al. Noninvasive face mask mechanical ventilation with acute hypercapnic respiratory failure. Chest 1991; 100: 445-54

18 patients with AHRF from a variety of causes. Managed to avoided formal intubation and ventilation in 13/18. Noted that success characterised by rapid improvement in pCO2 and pH. Failures were due to inablility to oxygenate and failure to clear retained secretions.

Marino W. Intermittent volume cycled mechanical ventilation via nasal mask in patients with respiratory failure due to COPD. Chest 1991; 99: 681-4

13 patients with AHRF from a variety of causes (10 had COPD). They used a volume cycled ventilator via a nasal mask. 7/13 patients improved and avoided the need for intubation. Two of patients who failed had central hypopnoea.

Pennock BE, Kaplan PD, Carlin BW, et al. Pressure support ventilation with a simplified ventilatory support system administered with a nasal mask in patients with respiratory failure. Chest 1991;100: 1371-6

31 patients with AHRF from a variety of causes. Used a BiPAP ventilator via a nasal mask and acheived a 76% success rate at avoiding ventilation.

NIPPV in Acute Respiratory Failure: Negative studies

There have been many more studies supporting the use of NIAV in AHRF than negative ones.

Chevrolet J, Jolliet P, Abajo B, et al. Nasal positive pressure ventilation in patients with acute respiratory failure. Difficult and time-consuming procedure for nurses. Chest 1991; 100: 775-782

6 patients with AHRF. Only successful in patients with restrictive lung disease (3/6). They found that the technique was very time consuming for nurses (COPD patients required nursing staff presence >90% of the time).

Foglio C, Vitacca M, Quadri A, et al. Acute exacerbations in severe COLD patients. Treatment using positive pressure ventilation by nasal mask. Chest 1992; 101: 1533-8

Retrospective study of 49 patients with acute exacerbations of COPD. They compared standard therapy (ST) alone vs. ST+NIPPV. Patients selected according to whether they could tolerate NIPPV(!!). Thye used a volume cycled ventilator via a nasal mask. Patients were kept in for 3 weeks (!!!). They found no difference at 10 & 21 days in pCO2, pO2, spirometry and dyspnoea scores.

Problems with the early studies

Mostly observational uncontrolled non-randomised retrospective studies.

Not all were specific to acute HRF in COPD.

Reports mostly from France and USA where criteria for ventilation and continuing active treatment in COPD differ from UK practice.

Not all patients were very sick (i.e. decompensated with low pH).

Differing techniques and equipment employed,

Varying durations of treatment (1-15 hours on 1st day for 1 to 21 days)

Used in different areas (i.e. ICU, HDU, open ward), with differing levels of paramedical support.

NIAV in Acute Respiratory Failure: The randomised controlled trials

Bott J, Carroll MP, Conway JH, et al. Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease. Lancet 1993; 341: 1555-7

60 patients with AHRF secondary to COPD randomised to standard therapy (ST) or ST+NIPPV via nasal mask with a pressure controlled ventilator (Brompton PneuPac). The NIPPV group did significantly better in terms of pH and pCO2 and patients were less breathless on NIPPV. Mortality was 3/30 in NIPPV vs. 9/30 in ST (significant on intention to treatment analysis), but only in 1/26 in NIPPV group in actual terms. Length of stay was also reduced in the NIPPV group.

Kramer N, Meyer TJ, Meharg J, et al. Randomised prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. AJRCCM 1995;151: 1799-806

31 patients, mostly AHRF secondary to COPD. Intubation and ventilation rate was rate 9% in the NIPPV group vs. 67% with ST. All physiological parameters better in the NIPPV treated group and nursing time same in both groups.

Brochard L, Mancebo J, Wysocki M, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. NEJM 1995;333: 817-22

The biggest study to date. 85 patients with AHRF secondary to COPD. They compared ST with ST+NIAV with pressure support via full face mask. Primary end point was intubation and formal ventilation. This was required in 26% of the NIAV group vs. 74% in ST group. Complication rate was also significantly lower in the NIAV group: 16% vs. 48% in ST group. Length of stay was also signiifcantly lower: 23 days NIAV vs. 35 days ST as was mortality: 9% NIAV vs. 29% ST.


NIAV in acute HRF

First published Mar 1998 

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