CHAPTER 8

Where to perform noninvasive ventilation?

J.V.J. Lightowler, M. Latham, M.W. Elliott

St James’s University Hospital, Leeds, UK.

Correspondence: M.W. Elliott, St James’s University Hospital, Beckett Street, Leeds, LS9 7TF, UK.

Noninvasive positive pressure ventilation (NPPV) has been shown to be an effectivetreatment for ventilatory failure, particularly resulting from acute exacerbations ofchronic obstructive pulmonary disease (COPD) [1–8], but also hypoxaemic respiratoryfailure [9], community acquired pneumonia [10], cardiogenic pulmonary oedema (CPO)[11] and following solid organ transplants [12] in 12 randomized controlled trials (RCTs).There have also been two RCTs of NPPV in weaning [13, 14]. Most striking is areduction in the need for intubation, which in the larger studies translates into improvedsurvival [2, 15] and reduced complication rates and length of both intensive care unit(ICU) and hospital stay [2]. Complications, particularly pneumonia and other infectiouscomplications are markedly reduced [2, 9, 12, 13]. The use of NPPV opens up newopportunities in the management of patients with ventilatory failure, particularly withregard to location and the timing of intervention. With NPPV paralysis and sedation arenot needed and ventilation outside the ICU is an option; given the considerable pressureon ICU beds in some countries, the high costs and that for some patients admission toICU is a distressing experience [16] this is an attractive option.

Definitions

In any discussion about location of an NPPV service it is important to note that themodel of hospital care differs from country to country and that "ICU", "high dependencyunit (HDU)" and "general ward" will have different levels of staffing, facilities formonitoring etc. Care must therefore be taken in the extrapolation of results obtained inone study environment to other hospitals and countries. The King’s Fund panel [17]define intensive care as: "a service for patients with potentially recoverable diseases whocan benefit from more detailed observation and treatment than is generally available inthe standard wards and departments". This broad definition does not unfortunately assistin the problem of comparisons of individual ICUs between studies. The definition ofHDU is even less clear with some HDUs allowing invasive monitoring whilst in othersonly noninvasive monitoring is performed. A recent multicentre study [15] of NPPV inacute exacerbations of COPD on general respiratory wards illustrates the large variationin nurse to patient ratios in different centres. In this study the mean nurse to patient ratiowas 1:11 with a range of 1:2.6–1:13.

For the purpose of this article the following definitions are used: 1) Intensive care orHDU implies continuous monitoring of vital signs with a ratio of at least one nurse tofour patients throughout a 24 h period in a specified clinical area. 2) A general ward takesunselected emergency admission and although most will have a particular specialityinterest it is likely that, because of the unpredictability of demand, patients with a varietyof conditions and degrees of severity will be cared for in the same clinical area. Nurse

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staffing levels will vary but the intensity of nursing input available on high dependencyand ICUs will not be possible.

Where to perform noninvasive positive pressure ventilation

Most of the RCTs have been in patients with COPD which will therefore be the mainfocus for the discussion about location of an acute NPPV service. The ICU is the usualsetting for noninvasive ventilation (NIV) although there have been five prospectiverandomized controlled studies of NPPV outside the ICU [1, 4, 5, 8, 15]. Bott et al. [1]randomized 60 patients with COPD to either conventional treatment or NPPV. NPPVinitiation, by research staff, took 90 min on average (range 15 mins–4 h) and it led to amore rapid correction of pH and carbon dioxide tension in arterial blood (Pa,CO2). In theconventional treatment group 9 of the 30 patients died compared to 3 of 30 in the NPPVgroup. On an intention-to-treat analysis these figures were not statistically significant,but when those unable to tolerate NPPV were excluded a significant survival benefit wasseen (nine of 30 versus one of 26, p=0.014). Generalizabilty from this study, althoughperformed on general wards, to routine practice is difficult given that staff additional tothe normal ward complement set up NPPV. The high mortality rate (30%) in the controlgroup was surprising considering that the mean pH was only 7.34. In addition the lowintubation rate, while probably reflecting UK practice, has been criticized.

Barbe et al. [4] initiated NPPV in the emergency dept in patients presenting with anacute exacerbation of COPD and continued it on a general ward. To ease some of theproblems of workload and compliance NPPV was administered for 3 h twice a day. Inthis small study (n=24) there were no intubations or deaths in either group and arterialblood gas tensions improved equally in both the NPPV group and in the controls.However the mean pH at entry in each group was 7.33 and at this level of acidosissignificant mortality is not expected; in other words it was unlikely that such a smallstudy would show an improved outcome when recovery would be expected anyway [18].

Wood et al. [5] randomized 27 patients with acute respiratory distress, due to a varietyof different conditions, to conventional treatment or NPPV in the emergency dept.Intubation rates were similar (seven of 16 versus five of 11) but there was a nonsignificanttrend towards increased mortality in those given NPPV (four of 16 versus 0 of 11,p=0.123). The authors attributed the excess mortality to delay in intubation asconventional patients requiring invasive ventilation were intubated after a mean of 4.8 hcompared to 26 h in those on NPPV (p=0.055). It is difficult to draw many conclusionsfrom this study given its small size, the fact that the number of patients in each group wasdifferent, the patients were not matched for aetiology of respiratory failure and the levelof ventilatory support was very modest (inspiratory positive airway pressure 8 cmH2O).

Angus et al. [8] compared NPPV and doxapram in patients with COPD and type IIrespiratory failure in a small (n=17; nine in NPPV group, eight in Doxapram group)randomized trial on a general ward. NPPV resulted in a significant improvement in bothoxygen tension in arterial blood (Pa,O2) and Pa,CO2 at 4 h. In contrast no fall in Pa,CO2

occurred in those patients treated with doxapram and an initial improvement in Pa,O2 wasnot sustained at 4 h. At both 1 and 4 h pH was significantly better in the NPPV group ascompared with the doxapram group. All the patients in the NPPV group were dischargedhome, although one required doxapram in addition to NPPV during their acute illness.Three of eight patients in the doxapram group died and a further two received NPPV. Thissmall study suggests that NPPV is more effective than doxapram in the treatment ofrespiratory failure associated with COPD. However no comparisons were made of nursingwork load, patient tolerance or complication rates between the two groups.

A multicentre RCT of NPPV in acute exacerbations of COPD (n=236) on general

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respiratory wards in 13 centres has recently been reported [15]. NPPV was applied, by theusual ward staff, using a bilevel device in spontaneous mode according to a simpleprotocol. "Treatment failure", a surrogate for the need for intubation, defined by a prioricriteria was reduced from 27% to 15% by NPPV (pv0.05). In hospital mortality was alsoreduced from 20% to 10% (pv0.05). Subgroup analysis suggested that the outcome inpatients with pHv7.30 after initial treatment was inferior to that in the studies performedin the ICU. There was no difference in length of stay between the groups, median 10 days(range standard group 2–119, NIV group 4–137, p=0.269). Because of a reduction in ICUutilization, NPPV was highly cost effective resulting in a saving of £4,114 for each deathavoided [19]. This study suggests that, with adequate staff training, NPPV can be appliedwith benefit outside the ICU by the usual ward staff and that the early introduction ofNPPV on a general ward results in a better outcome, and with cost savings, thanproviding no ventilatory support for acidotic patients outside the ICU. It must howeverbe put into an international perspective. In North America and in many Europeancountries, NPPV would not be considered an appropriate treatment for the wardenvironment. The fact that early intervention has been confirmed as having an advantagepotentially increases the number of patients with an exacerbation of COPD who shouldreceive ventilatory support. In the UK and other countries, in which ICU beds are inshort supply, if COPD patients are to receive NPPV it will usually be in the wardlocation, where nurses provide global care and can adopt some of the roles of therespiratory therapist. These features of the UK setting may reduce the generalizability ofthe mortality data to countries with good ICU provision. The study certainly does notsuggest that NPPV should be performed on a general ward in preference to an ICU or ahigher dependency setting.

There have been no direct comparisons between outcome from NPPV in the ICU andon a general ward and it is unlikely that there will ever be such a trial. It should beappreciated that while there is some overlap the skills needed for NIV are different tothose required for invasive ventilation and the outcome from NPPV is likely to be betteron a general ward where the staff have a lot of experience of NPPV than on an ICU withhigh nurse, therapist and doctor to patient ratios and a high level of monitoring, but littleexperience of NPPV. The patient’s perspective is also important; many find theirexperience of ICU to be unpleasant [16] and the less intensive atmosphere of anoninvasive unit may be less distressing, although there is no evidence to support thisassertion. The best location for a NPPV service will depend critically upon local factors,particularly the skill levels of doctors, nurses and therapists in looking after patientsreceiving NPPV. Patient throughput is an important factor which impacts upon thedevelopment, and retention, of the particular skills needed for NPPV. In a recent studyfrom the UK it has been suggested that for the average general hospital, serving apopulation of 250,000 and with a standardized mortality rate for COPD of 100, sixpatients per month with an acute exacerbation of COPD will require NPPV, assumingthat ventilation is initiated in patients with a pHv7.35 after initial treatment [20]. Thisnumber excludes patients with other conditions requiring NPPV and those who require itlater in their hospital stay, e.g. for weaning etc. With relatively small numbers of patientsper month, NPPV is best performed in a single sex location, to facilitate staff training andto maximize throughput and skill retention.

Implications for staffing

NIV has been reported to be a time consuming procedure [21] but as with any newtechnique there is a learning curve and the same group have subsequently published moreencouraging results [22]. A number of studies, on the ICU, have shown that certainly to

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start with a significant amount of time is required to establish the patient on NPPV[3–23]. It is possible therefore that NPPV may have a much greater impact on nursingworkload outside the ICU, where nurses have responsibility for a larger number ofpatients. In the study of Bott et al. [1] there was no difference in nursing workload,assessed by asking the senior nurse to rate, on a visual analogue scale, the amount of careneeded in the conventional and NPPV groups. However this is an insensitive way ofmeasuring nursing needs and in addition some of the potential extra work associated withNPPV was performed by supernumerary research staff. In the study of Plant et al. [15]NPPV resulted in a modest increase in nursing workload, assessed using an end of bed log,in the first 8 h of the admission, equating to 26 min, but no difference was identifiedthereafter. There is however no data on the effect NPPV has on the care that other patientson the ward received nor whether the outcome would have been better if the nurses hadspent more time with the patients receiving NPPV. In other words although this studyshowed that NPPV was feasible in the general ward environment it does not mean that itwas the optimal situation. Furthermore even if good results can be obtained it may be atthe expense of the care of other patients. Most of the centres that participated in the studyhad little or no previous experience of NPPV and therefore required training in maskfitting and application of NPPV. The mean amount of formal training given in the first 3months of opening a ward by the research doctor and nurse was 7.6 h (sd 3.6 h).Thereafter each centre received 0.9 h per month (sd 0.82) to maintain the skills. It shouldbe appreciated that there was no need to make subtle adjustments to ventilator settingswhich was all done according to protocol. Much more training would be needed if moresophisticated ventilators are used. However it underlines the fact that NPPV, in whateverlocation, is not just a question of purchasing the necessary equipment but also of stafftraining. Although a considerable amount of input is likely when a unit first starts toprovide a NPPV service thereafter, as long as a critical mass of nurses and therapistsremain, new staff will gain the necessary skills from their colleagues.

Predicting the outcome with noninvasive positive pressureventilation

A proportion of patients will fail with NPPV, requiring intubation and invasiveventilation; it is important that personnel and the facility for intubation be rapidlyavailable if needed, if the trend to increased mortality with NPPV, as reported by Wood

et al. [5] is to be avoided. It could be argued that for patients with a high likelihood offailing, NPPV should be initiated on the ICU and once stabilized the patient could betransferred to the ward normally providing NPPV. It is therefore helpful to be aware ofwhen NPPV is likely to fail since this may affect the decision as to the most appropriatelocation for NPPV in a particular patient. A number of studies have looked at predictorsof outcome for NPPV in acute exacerbations of COPD [1, 2, 24, 25–30]. The majorlimiting factors is that prediction models are only as good as the data entered; data that isnot collected cannot be entered into the model. Furthermore the chosen outcome mayinfluence the results. For instance if failure of blood gas tensions to improve within acertain time is taken as an indication for intubation then this will, by default, become afailure criterion even if perhaps with persistence and adjustment of ventilator settingssuccess with NPPV could have been achieved.

Severity of illness at baseline

Two studies [2, 24] have shown an association between baseline arterial blood gastensions and response to NPPV. In a retrospective review aimed at identifying patients

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with COPD who could be successfully treated with NPPV Ambrosino et al. [24] foundthat patients failing NPPV were significantly more acidaemic at baseline compared withthose successfully treated (pH 7.22 (sd 0.08) versus 7.28 (sd 0.04), pv0.005). Althoughusing a discriminant analysis a number of variables (neurological status score, AcutePhysiology and Chronic Health Evaluation (APACHE) II, baseline pH, Pa,CO2 and pHduring NPPV) had a predictive value ofw0.80 for successful NPPV, when tested togetherusing logistic regression analysis, only baseline pH maintained a significant predictiveeffect with a sensitivity of 97% and specificity of 71%. Similarly Brochard et al. [2], usinga priori criteria for the need for intubation, found that success was less likely the lower thestarting pH. A number of other studies however have failed to show any suchrelationship [25–30]. Patients failing NPPV have been shown to have more severe illnessat presentation, as judged by the APACHE II scores, compared with those successfullytreated in two studies (21¡4 versus 15¡4, p=0.02 [29], 29¡4 versus 18¡4, pv0.0001 [24]),but other studies have failed to support these results [26, 27, 30]. Using the SimplifiedAcute Physiology Score (SAPS) Benhamou et al. [28] also found no difference betweensuccessful and unsuccessful NPPV in their study of elderly patients with acute respiratoryfailure (ARF) and a variety of underlying lung pathologies. An altered level ofconsciousness has been suggested to be a contra-indication to NPPV [31], although this islargely for theoretical reasons and because such patients have usually been excluded fromclinical trials. A better level of consciousness at baseline [24, 30] and after 1 hr of NPPV[30] has been shown to correlate with success. Brochard et al. [2] also noted that theencephalopathy score dropped significantly in patients successfully treated with NPPVduring the course of their treatment. Again other studies have failed to show such arelationship [27, 28, 32].

The patient’s general condition

Ambrosino et al. [24] found that patients failing with NPPV tended to be underweightand to have significantly lower forced vital capacity (FVC) than their successfulcounterparts. Pulmonary function test (PFT) results were, however, only available in justover two-thirds of patients. Surprisingly Anton et al. [30] found that a successfuloutcome with NPPV was more likely with a lower forced expiratory volume in onesecond (FEV1) (27¡11 versus 38¡11% predicted pv0.01). The cause of the acuteexacerbation is also not a reliable predictor of outcome from NPPV [24, 26, 28–30]. Intwo studies [24, 29] radiological consolidation was more common in the group failingNPPV but in a prospective randomized controlled trial, evaluating NPPV againstconventional treatment in patients with pneumonia, Confalonieri et al. [10] found thatin the subgroup of patients who also had COPD the 2 month survival was better in theNPPV group. There is also evidence suggesting that age should not be a bar to NPPV,with elderly patients being successfully treated [28].

Tolerance and physiological effect of noninvasive positive pressure ventilation

The ability of the patients to tolerate NPPV is an important factor which maydetermine the likely outcome of treatment. Indeed Benhamou et al. [28] found that"tolerance" of NPPV was the only factor of prognostic value. Ambrosino et al. [24] alsofound that better compliance was associated with a greater likelihood of success withNPPV and in their prospective case series of 12 patients with hypercapnic ARF Soo Hoo

et al. [29] noted that successfully treated patients were able to tolerate NPPV for longerthan the patients who could not be successfully treated. Patients failing with NPPVtended to be edentulous, to breathe through pursed lips and to have larger volumes of air

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leak compared to those successfully treated [29]. A number of studies have shown thatthe change in arterial blood gas tensions, particularly pH, after a short period of NPPVpredicts a successful outcome [1, 2, 24–26, 29]. An improvement in pH and/or Pa,CO2 at30 min [27], 1 h [25] or after a longer period [25, 29] predict successful NPPV. Patientswho have been intubated and are likely to fail a weaning attempt adopt a pattern of rapidshallow breathing when disconnected from the ventilator [33], indicating that they arebreathing against an unsustainable load. A reduction in respiratory rate with NPPV hasbeen variably shown in a number of studies, with larger falls generally being associatedwith a successful outcome from NPPV [2, 25, 29] though this is not always seen [30]. Inthe absence of a priori criteria for endotracheal intubation it is not surprising that afailure of commonly measured physiological variables to improve prompts an escalationof therapy, which in this case is a switch to invasive ventilation.

Data available at the time NPPV is initiated and after a short period can predict thelikelihood of success or failure with a reasonable degree of precision. The severity ofacidosis at baseline emerges as an important predictor; although NPPV is less likely to beeffective when patients are more acidotic [2, 24] this should not preclude a trial of NPPVas the mode of ventilatory support of first choice because the benefits of NPPV comparedwith intubation and mechanical ventilation are greater [2]. The tolerance of NPPV andthe change in arterial blood gas tensions, particularly pH, and respiratory rate in theearly hours are reasonable predictors of the subsequent outcome [1, 2, 24, 34]. NPPV isless likely to be successful if there are associated complications or if the patient’spremorbid condition is poor [34]. These factors in addition to others summarized intable 1 will have a bearing upon the chosen location for NPPV, though it must bestressed again that local factors more than any other will be the key determinants.

Should noninvasive positive pressure ventilation be started in the emergencyroom?

Again the type of treatment that is undertaken in the emergency room and the lengthof time that patients typically stay there varies from country to country. Some patientsremain in the emergency room for a very short period whereas others may remain therefor i1 day. The two studies in which NPPV was initiated in the emergency room [4, 5]both failed to show any advantage to NPPV over conventional therapy. There are anumber of possible explanations for this, but include the fact that patients are usuallyadmitted to ICU when other therapies have failed whereas most of those presenting tothe emergency room have not received any treatment; a proportion are going to improveafter initiation of standard medical therapy. In a 1-yr period prevalence study [20] ofpatients with acute exacerbations of COPD of 954 patients admitted through theemergency rooms in Leeds, 25% were acidotic on arrival in the Dept and of these 25%had completely corrected their pH by the time of arrival on the ward. There was a weakrelationship between the Pa,O2 on arrival at hospital and the presence of acidosis,suggesting that in at least some patients, respiratory acidosis had been precipitated byhigh flow oxygen therapy administered in the ambulance on the way to hospital. It isimportant to note that the Yorkshire Noninvasive Ventilation (YONIV) study, the only

Table 1. – Reasons why a successful outcome from noninvasive positive pressure ventilation (NPPV) is lesslikely

Poor premorbid health statusPresence of complicationsLow pH at baselineNo change in pH and respiratory rate after a short trial of NPPV

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study to show an unequivocal benefit from NPPV outside the ICU, only recruitedpatients who remained acidotic and tachypnoeic on arrival on the ward.

There are some patients who present to the emergency room in extremis and requireimmediate ventilatory support for whom intubation is not considered appropriate,because the patient’s previous history is well known, but for whom a trial of NIV wouldbe considered. In this situation it would be reasonable to start NIV in the emergencyroom to stabilize the patient for transfer to the ward on which NPPV is normallyperformed. In other patients the clinical findings suggest that intubation would not beappropriate, but the medical notes or a family member are not available to corroboratethis. NPPV may be useful in this situation to buy time in which to obtain furtherinformation or to allow the patient to recover to the point at which they can give ahistory. However if there is no improvement the patient should be intubated andtransferred to the ICU.

In summary most patients presenting to the emergency room with an acuteexacerbation of COPD do not need NPPV, but particular attention should be paid tocontrolled oxygen therapy. NPPV may be needed in occasional patients who are inextremis and for whom intubation is not considered appropriate. If it is normal policy forpatients to receive the first 24 h treatment in the emergency department then NPPVshould be started there in those who remain acidotic and tachypnoeic a short time afterstandard medication has been administered and oxygen therapy optimized.

Conditions other than chronic obstructive pulmonary disease

There are no RCTs of NPPV outside the ICU in hypoxaemic respiratory failure orweaning and it is therefore only in patients with exacerbations of COPD that there is anevidence base for its use outside of the ICU. The study of Antonelli et al. [9] in whichconventional mechanical ventilation (MV) and NPPV were compared in patients withacute hypoxic respiratory failure, showed NPPV to be as effective as conventionalventilation in improving gas exchange. Patients receiving NPPV had significantly lowerrates of serious complications and those successfully treated with NPPV had shorter ICUstays. Post hoc subgroup analysis of patients with SAPS ofv16 and those of i16 showedthat patients in the latter group had similar outcomes irrespective of the type ofventilation. However NPPV was superior to conventional MV in patients with SAPSv16. Confalonieri et al. [10] evaluated the early application of NPPV in patients withacute respiratory failure due to severe CAP, on three intermediate respiratory ICUs.Twenty-eight patients were randomly assigned to standard treatment and 28 to NPPV.NPPV resulted in a significant reduction in intubation. Six patients (21%) in the NPPVgroup and 17 (61%) in the standard treatment group met the preselected criteria forintubation (p=0.007). Twenty patients in total were intubated, six in the NPPV group and14 in the standard treatment group (p=0.03). The three remaining patients in the standardtreatment group, who met the preselected criteria for intubation but were not intubated,were all successfully treated with NPPV. Patients randomized to NPPV had significantlyshorter ICU stays (1.8¡0.7 days versus 6¡2 days p=0.04) and required similar nursingcare intensity to those in the standard treatment group. The two groups did notsignificantly differ in terms of duration of hospital stay, complications, hospital and 2month mortality. Post hoc analysis of the subgroup of patients without COPD showedthat a high APACHE II score was significantly associated with intubation requirement(p=0.004) and hospital (p=0.04) and 2 month mortality (p=0.03) but was not anindependent predictor of outcome. As with acute exacerbations of COPD it wouldtherefore appear that it is possible to successfully manage patients with milder diseasewith NPPV. Further data are needed but it would be reasonable for patients with milder

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disease to have a trial of NPPV on an experienced noninvasive unit outside the ICU;rapid access to intubation and MV must be available.

Three RCTs have been performed comparing standard medical treatment pluscontinuous positive airway pressure (CPAP) and standard medical treatment alone inpatients with CPO [35–37]. The earliest of these studies [35] showed significantimprovement in oxygenation within the first 10 min of treatment, in the patientsrandomized to 10 cmH2O of CPAP as compared with the control group. Seven of 20patients in the CPAP group and 13 of 20 in the standard treatment group failed(p=0.068). There was also no difference in mortality rates between the two groups. Thelargest study [37] involved 100 patients (50 in each group) admitted to a coronary careunit with acute pulmonary oedema. Haemodynamic and pulmonary function parameterswere recorded over the first 6 h following admission. Using predetermined criteria,CPAP resulted in a reduced intubation and therapeutic failure rates at 6 h (eight of 50versus 18 of 50, pv0.01 and 12 of 50 versus 25 of 50, pv0.01, respectively). During the firstthree hours the CPAP group also showed significant improvements in oxygenation,alveolar arterial oxygen gradient and intrapulmonary shunt, a lower rate-pressureproduct and a higher stroke-volume index as compared with the control group. Therewas, however, no difference in hospital or 1-yr mortality or hospital length of staybetween the groups. Bersten et al. [36] randomized 39 patients admitted to ICU withacute CPO to receive standard medical care (n=20) or CPAP (n=19). At enrolment thepatients were more acidotic than those in the other two RCTs (pH 7.18¡0.08 CPAP,7.15¡0.11 control). Receiving a total of 9.3¡4.9 h per day of CPAP led to a reduction inintubation rate (seven of 20 versus 0 of 19, p=0.005), a shorter ICU stay (1.2¡0.4 daysversus 2.7¡2.0 days, p=0.006) and more rapid improvement in respiratory rate,respiratory acidaemia and oxygenation. Again there was no difference in mortalityrate between the two groups.

Pooled results of these three RCTs [38] show a risk reduction for intubation of 26%(95% confidence interval (CI) 14–38%) with CPAP indicating that four patients withpulmonary oedema need to be treated with CPAP to prevent one intubation. The pooledresults also suggest a trend towards a reduction in hospital mortality, with a riskdifference of 6.6% between the two treatment groups however the confidence intervalswere wide (95% CI -16–3%) and thus do not allow the exclusion of harm with CPAPtreatment.

Only one study has compared bilevel positive airway pressure (BiPAP) and CPAP inthe treatment of acute pulmonary oedema [11]. Performed in the emergency dept setting,this study of 27 patients showed that BiPAP improved ventilation and vital signs morerapidly than CPAP. At 30 min the BiPAP group had significant improvements in pH,Pa,CO2, respiratory and heart rates and dyspnoea scores. In contrast only respiratory rateimproved, from baseline values, in the patients treated with CPAP. When the twotherapeutic groups were compared a greater reduction in Pa,CO2 was seen in the BiPAPgroup although this failed to reach a significant level (p=0.057). The BiPAP group didhowever have a significantly greater reduction in systolic (p=0.005) and mean bloodpressure (p=0.03). The outcome variables were similar in both groups, with no differenceor trends towards difference in intubation rates (7% versus 8%, p=ns), mortality rates (7%versus 15%, p=ns) and ICU or hospital length of stay. The study was terminated early,following interim analysis, because of an increased rate of myocardial infarctions in theBiPAP group (10 of 14 versus four of 13, p=0.06). Baseline characteristics of the twogroups of patients were well matched except for a higher, although nonstatisticallysignificant, incidence of chest pain (10 of 14 versus four of 13, p=0.06) and left bundlebranch block on the electrocardiogram (ECG) in the BiPAP group. It is therefore unclearas to whether the increased infarction rate is due to BiPAP ventilation per se, the specificsettings used or due to the higher incidence of chest pain at the outset. Further larger

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studies are therefore needed but if NPPV or mask CPAP are to be used it will need to beinitiated in the emergency room or on ICU/HDU/coronary care unit (CCU).

Starting noninvasive ventilation on a general ward

Nursing and technical staff should be adequately prepared (table 2) and the necessaryequipment must be available before NPPV is first tried. To start the following isrecommended: 1) A simple ventilator, pressure cycled machines are usually simple,compensate for moderate leaks and are generally better tolerated by patients. A supply ofcircuits already made up. 2) A range of sizes (at least three) of masks, both nasal andfull face, and head gear. A minimum of two of each should always be available. 3)Connectors to allow customization of ventilator circuits e.g. for entrainment of oxygen.4) Facility for cleaning masks, circuits and headgear to an acceptable standard (i.e. wash/disinfection at 80‡C or a budget to allow single patient use of these items).

Staff should use the equipment on each other in a nonclinical setting and practise thetheoretical knowledge and skills prior to use on real patients. Two or three enthusiasticstaff are a real boon as they will often carry the rest of the team with them. Nurses withprevious experience of ICU or NPPV are particularly useful since they will be confidentwith ventilators. If such individuals are not available within the existing complement,recruitment of such an individual should be considered. An experienced practitionershould be available 24 h a day to help sort out problems until staff are able to solve themthemselves. As experience is gained further types of ventilator, new masks etc. can beadded widening the range of patients who can be successfully ventilated noninvasively.

Conclusion

Staff training and experience is more important than location, and adequate numbersof staff, skilled in noninvasive positive pressure ventilation, must be available throughoutthe 24-h period (table 3). Because of the demands of looking after these acutely illpatients, and to aid training and skill retention, noninvasive positive pressure ventilationis usually best carried out in one single sex location with one nurse responsible for nomore than three to four patients in total. Whether this is called an intensive care unit, a

Table 2. – Training requirements

Understanding rationale for assisted ventilationMask and headgear fitting techniquesVentilator circuit assemblyTheory of operation and adjusting ventilation to achieve desired outcomeCleaning and general maintenanceProblem solving, the ability to recognize serious situations and act accordinglyAbove all medical, nursing and technical staff need to be convinced that the technique works

Table 3. – Where should noninvasive positive pressure ventilation be carried out?

Factors to be considered:Location of staff with training and expertise in noninvasive ventilationAdequate staff available throughout 24 h period (will depend upon nursing needs of other patients, for instance

one nurse responsible for two very ill patients may have less time than one nurse responsible for four lessseverely ill patients)

Rapid access to endotracheal intubation and invasive mechanical ventilationSeverity of respiratory failure and likelihood of successFacilities for monitoring

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high dependency unit or is part of a general ward is largely irrelevant. Further studies areneeded to determine the optimal threshold for initiating noninvasive positive pressureventilation, particularly in conditions other than chronic obstructive pulmonary disease,to assess the feasibility, safety and effectiveness in lower intensity settings, and todetermine the cost-effectiveness both in the short and long term.

Summary

The use of noninvasive positive pressure ventilation (NPPV) in a wide variety ofconditions is now supported by a number of randomized controlled trials (RCTs). Thelargest evidence base is in it use in acute exacerbations of chronic obstructivepulmonary disease (COPD), with the majority of studies being performed in theintensive care unit (ICU) setting. These show a reduction in intubation rates, thenumber of complications and ICU/hospital length of stay and improved survival inpatients receiving NPPV. More variable results are obtained when NPPV is performedoutside the ICU. However in the largest ward based study NPPV led to both a reducedneed for intubation and mortality and was also highly cost effective.No advantage over conventional treatment is seen when NPPV is initiated in theemergency room. In this setting optimization of controlled oxygen therapy andstandard medication is usually adequate to ensure recovery.There have been no direct comparisons between ward based and ICU based NPPV.Although NPPV has been used with success on the ward it can not be implied that thisis the optimal situation. Predicting which patients are likely to fail NPPV will aid thedecision as to where it should be performed. A number of predictors of subsequentoutcome have been identified.Although NPPV is as effective as conventional treatment in improving gas exchangewhen performed on the ICU, no RCTs of NPPV outside ICU in hypoxaemicrespiratory failure or for weaning have been performed. Until such data is availableward based NPPV for these conditions should be performed with caution.The best location for a NPPV service will depend on local factors. Well-trainedexperienced staff with access to appropriate equipment is more important thanlocation per se. If NPPV is performed on a general ward access to the ICU should bereadily available so that intubation and invasive mechanical ventilation are notdelayed if NPPV fails.

Keywords: General ward, high dependency unit, intensive care unit, noninvasivepositive pressure ventilation, predictors, respiratory failure.

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