Introduction

Supplemental oxygen to ensure adequate delivery to vital organ functions is the primary goal of long-term oxygen therapy (LTOT) in patients with chronic hypoxemia at rest, during sleep and activity [1, 2]. The evidence supporting the current guidelines for LTOT still consists of two randomized clinical trials conducted in chronic obstructive pulmonary disease (COPD) patients and published in the early 1980s, i.e., the Nocturnal Oxygen Therapy Trial (NOTT) and the Medical Research Council (MRC) study [3, 4]. Although COPD guidelines are regularly updated (Global Initiative for Chronic Obstructive Lung Disease 2011 and National Clinical Guideline Centre 2010) [1, 2], the specific guidelines for LTOT remain unchanged over the years.

COPD patients who meet specific criteria for LTOT are likely to improve several functions such as hemodynamics, cognitive function, exercise capacity, and as well have a prolonged survival [1–4]. Specifically, patients with COPD and severe chronic hypoxemia (as defined as a partial pressure of arterial oxygen, PaO2, ≤55 mmHg) who use oxygen around the clock [2–5] or at least 15 h daily are more likely to survive longer.

The efficacy of LTOT in subjects with severe COPD and only moderate hypoxemia is still controversial. However, LTOT is recommended for these patients, even if this recommendation is not supported by the scientific evidence [5, 6]. In fact, the study of Gόrecka and colleagues, a 7-year randomized controlled trial, performed on 135 patients with COPD and moderate chronic hypoxemia (PaO2 56–65 mmHg), finds no difference of survival rates between patients receiving LTOT and controls [6]. Similarly, the role of supplemental oxygen in COPD patients with nocturnal desaturation and with exercise-induced hypoxemia is still unclear [7–10].

The LTOT guidelines [1, 2] suggest that the direct assessment of blood gases by means of an arterial puncture is the preferred method to determine the need of LTOT. In contrast, arterial oxygen saturation (SpO2), as measured by pulse oximetry, is not recommended for the prescription of LTOT, but only for monitoring its efficacy. Physiological indications for LTOT include PaO2 ≤55 mmHg (≤60 mmHg, in the presence of specific comorbidities), or SpO2 ≤88 % (≤90 %, in the presence of specific comorbidities) at rest and in a stable condition.

The burden of domiciliary LTOT in Italy is estimated at 4,500–6,500 Euros/patient/year, and globally accounts for approximately 250,000,000 Euros/year run by the Italian National Health System [11–14]. Considering these high costs, several clinical trials are ongoing to assess adherence and efficacy of LTOT [15].

Waiting for the results from these international clinical trials aiming to assess the proportion of patients not meeting criteria for prescribing LTOT, as well as the excessive prescription of LTOT, we decided to measure whether the LTOT prescriptions performed in two Italian university hospitals were adherent to guidelines. To this objective, we carried out a retrospective clinical audit to assess in a sample the prescription of LTOT in the years 2005–2006, with the aim to determine (1) the proportion of patients fulfilling criteria for LTOT, and (2) the adherence to guidelines of the prescription. The study was a part of the 2007–2009 University Research Program of the Emilia-Romagna regional government (Grant No. 2/2/2/8).

Methods

Patients

From January 2005 to December 2006, patients who were prescribed LTOT in the health system of the province of Ferrara (360,000 inhabitants) and in the health system of the province of Modena (700,000 inhabitants), Italy, were identified through the Oxygen Service administration database. The protocol for LTOT prescription, the Oxygen Service administration and the oxygen suppliers were the same in both areas on study. Out of 450 total prescriptions in the 2 years, we were able to assess the medical files of 191 patients.

From each medical record, we extracted patient demographic characteristics, diagnosis, cause of chronic hypoxemia, concomitant diseases, smoking history, resting PaO2 and/or SpO2 on air, clinical diagnosis requiring the prescription of oxygen, adherence of the prescription to the guidelines in terms of (1) number of hours/day prescribed by physician, (2) type of oxygen delivery system (oxygen concentrator or in form of compressed gas or liquid oxygen), and (3) qualification of the medical prescriber (pulmonologist or other specialists). The compliance of patients in terms of number of hours/day of oxygen administration was verified by the measure of overall consumption of oxygen as reported by the oxygen suppliers. With the exception of patients who had died before the audit, we interviewed the patients in clinic or by telephone.

The study was classified as an audit of clinical records by the local research Ethics Committee, and thus, a written informed consent was not required.

Criteria definition

The adherence to current guidelines for LTOT [1, 2] was verified over two main criteria: appropriateness of prescription, and compliance to treatment.

Prescription of LTOT was defined appropriate if PaO2 was ≤55 mmHg (≤60 mmHg in the presence of specific comorbidities) or SpO2 ≤88 % (≤90 % in the presence of specific comorbidities) (Fig. 1). Patients with adequate clinical records (arterial blood gas or pulse oximetry measurement, oxygen administration, smoking status) were considered eligible (157 out of 191 patients).

Fig. 1
figure 1

Indications and criteria for evaluating the appropriateness of prescription in patients on long-term oxygen therapy; PaO 2 partial pressure of arterial oxygen, SpO 2 arterial oxygen saturation

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Patients were defined as compliant to LTOT when the consumption of oxygen (prescribed by the physician and verified by the oxygen suppliers) was ≥15 h/day. Voluntary or involuntary waste of oxygen could not be excluded. In addition, we also assessed the smoking status.

Statistical analysis

All analyses were performed using the Statistical Package of Social Sciences ver. 13 (SPSS Inc, Chicago, IL, USA). Frequency analyses, contingency tables, the χ2 test, Mann–Whitney test, and analysis of variance (ANOVA) were used as appropriate. A p value of <0.05 was considered significant.

Results

A total of 191 patients, 109 men and 82 women, were included in the study. At the time of the audit, the patients who had died were 15 out of 191 patients (7.8 %). PaO2 and SpO2 were not available in 17.8 % of subjects. Patients with adequate clinical records to assess adherence (arterial blood gas or pulse oximetry measurement, oxygen administration, smoking status) were considered eligible (157 of 191 patients).

Patient characteristics are shown in Table 1. At the time of prescription, the mean age was 75 years. Of the study participants, 21 % were non-smokers, 44.5 % were ex-smokers (mean, 42.8 pack/years), and 13.6 % continued to smoke, even if the current smoking is considered to be an absolute contraindication to supplemental oxygen. Details of smoking status were not available in 21 % of the eligible subjects. Body mass index (BMI) was slightly high as mean value, with a considerable proportion of obese patients (31 %). The main reason for LTOT prescription was a pulmonary disease (80.6 %), followed by other diseases (7.3 %), obstructive sleep apnea syndrome (OSAS) (4.7 %), and neuromuscular disorders in 2.1 %. In the last two conditions, LTOT was prescribed in combination with mechanical ventilation. The cause of chronic hypoxemia was not reported in 5.2 % of patients. Among the patients with pulmonary disease, COPD was the commonest reason for prescription. Most patients had concomitant cardiac diseases, particularly cardiovascular, including congestive heart failure, pulmonary hypertension, cor pulmonale, and polycythemia that may also be considered as reasons for prescription of LTOT (Table 1).

Table 1 Patient characteristics in the study population (N = 191 patients)
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Appropriateness of oxygen prescription

Long-term oxygen therapy was mainly administered in the form of liquid oxygen (94.2 %). In patients with documented arterial blood gas measurements (N = 135 patients), 44 (32.6 %) had a PaO2 >55 mmHg, 82 (60.7 %) had a PaO2 ≤55 mmHg, and 9 (6.6 %) had a PaO2 56–60 mmHg associated with cor pulmonale, pulmonary hypertension, congestive heart failure, or polycythemia.

In patients with documented pulse oximetry only (N = 22), LTOT was prescribed appropriately (SpO2 ≤88 %) in only eight patients (36 %). Thus, in patients with arterial blood gas assessment or pulse oximetry available (N = 157 patients), subjects who met the criteria for LTOT were only of 63 %.

Out of the study population (N = 191), 168 patients (88 %) had data on oxygen consumption: 23 (13.7 %) were prescribed oxygen for <15 h daily (5–14) and 145 (86.3 %) for ≥15 (15–24) h/day. A small group of patients (4 out of 168 patients, 2 %) received oxygen ≤15 h/day for palliative care.

Eleven out of the 15 deceased patients were appropriately prescribed LTOT.

LTOT was prescribed by specialists in pulmonary diseases (pulmonologist) in 64.5 % of the patients, by specialist in internal medicine (internist) in 29.3 %, and by other specialists in 6.2 % of patients. All prescribers worked full time at the Hospital.

Considering the values of PaO2 or SpO2 only, the specialty of the prescriber had no impact on the appropriateness of the prescription. In fact, the proportion of patients who were appropriately prescribed LTOT according to the PaO2 or SpO2 values was 68.6 % if prescribed by a pulmonologist, as compared to 54.2 % if prescribed by an internist, and 43 % by others. In contrast, the proportion of patients who were prescribed LTOT ≥15 h/day was higher (60 %) if prescribed by a pulmonologist, as compared to an internist (23 %). Overall, considering all three criteria recommended (values of PaO2 and/or SpO2, number of hours/day, and smoking status), the proportion of the patients appropriately prescribed was significantly higher whether the referring physician was a pulmonologist (p = 0.03, Fig. 2).

Fig. 2
figure 2

Appropriateness of prescription according to arterial blood gas or pulse oximetry, number of hours/day prescribed, and smoking status. Comparison of prevalence in each group of prescribers in patients with complete medical records (N = 157)

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The overall proportion of patients prescribed LTOT according to all three criteria, i.e., need for supplemental oxygen determined by values from arterial blood gas measurement or pulse oximetry, appropriate prescription for oxygen administration at least 15 h daily, and smoking status (patient never or former smoker), was only 73 out of 157 patients (46.5 %).

Discussion

The results of this audit suggest that LTOT is inappropriately prescribed in a large proportion of patients (37 %) with documented PaO2 and/or SpO2, who in fact did not meet (PaO2 or SpO2 values) the criteria for recommending it. In addition, we also found that another significant proportion of patients received LTOT without even measuring PaO2 or SpO2 values. Furthermore, even in patients who met the criteria for LTOT, up to 14 % were prescribed LTOT for less than 15 h/day. In total, after evaluating all prescriptions, only 46.5 % fulfilled all criteria, i.e., need for supplemental oxygen according to guidelines, LTOT >15 h/day, and a non-smoking status.

Our major finding is that 44 of 135 patients (32.6 %) have PaO2 >55 mmHg. Ringbaek et al. shows a rate of 24 % of inappropriate values of PaO2 in patients on LTOT in their Danish study [16]. The proportion is slightly higher (45 %) in the report by Veale and colleagues [17] and lower (19 %) in the study by Morrison et al. that reviewed home oxygen prescriptions in Scotland, where arterial blood gas measurement was not performed in 15 % [18]. We also show that the proportion of prescriptions fitting all criteria for LTOT (physiological parameters, duration of daily oxygen therapy, and smoking status) is less than 50 %. Ringbaek et al. have reported even a lower rate, i.e., 34 % [16].

The clinical benefits of LTOT depend on the daily duration of oxygen use. In comparison with the findings from other authors, in the present study, the adherence to guidelines was good: in fact, almost all patients (86.3 %) were prescribed for ≥15 h/day. Similar results were reported in the French study, the daily duration of treatment was at least 15 h daily in 82 % of patients [17]. In the Danish studies, only 50 % of the patients on LTOT were appropriately prescribed ≥15 h/day [16, 19].

In the present study, we still have a significant proportion of patients (13.6 %) who continue to smoke. This percentage is similar to what is reported in the previous studies. Guyatt et al. find 10.3 % of current smokers [20]. In two other studies, 21 and 26 % of patients continued to smoke at prescription time, respectively [16, 21]. A recent survey of Canadian pulmonologists on clinical practice regarding indications and prescription of nocturnal oxygen therapy in COPD patients, shows that 41 % of physicians would prescribe nocturnal oxygen or LTOT to active smokers [22]. It is still unclear whether LTOT is efficacious in patients who continue to smoke. Considering the risk of continuous smoking in patients prescribed LTOT, it might be useful to recommend regular measurements of CO-Hemoglobin, easily possible using commercial blood gas analysers, or exhaled CO.

While the local guidelines recommend the least expensive system (i.e., oxygen concentrator) unless the physician requests otherwise, we observe that the majority of patients (94.2 %) are prescribed the most expensive oxygen delivery system suggesting that the physicians paid little attention to the cost of LTOT.

This is the first study that systematically assesses the appropriateness of LTOT in Italy. The study was designed as a survey, i.e., as assessment of medical record, and nonetheless showed significant inappropriateness. We did not check the accurateness of measurements and compliance. Most previous studies were designed to assess costs, quality of life, or survival outcomes [13, 23–25].

As the incidence of COPD grows, prescription of LTOT increases in Europe, North America and Asia [26, 27]. As expected, most patients receiving LTOT have a diagnosis of COPD (62.3 %). However, a significant proportion of patients had different diagnoses. Given that no benefit occurs when long-term oxygen administration is for patients not fulfilling all of the relative criteria for the prescription, assessment of appropriateness is important for both patient care and economic costs.

Most likely the large proportion of inappropriate LTOT is due to limited knowledge of the scientific literature and guidelines, and lack of specific continuous medical education. The large proportion of inappropriateness suggests the need of intense educational activities in training health operators in charge of LTOT.

This study has several limitations. The major limitations are the nature of the study (analysis of medical records), and the limited sample of medical records analyzed that makes the results difficult to generalize to all local, regional or national prescriptions. Nonetheless, the study provides an important preliminary information to design and perform more accurate and larger studies. Another limitation of the study is the proportion of missing PaO2 or SpO2 data (17.8 %), even if patients’ characteristics (demographic characteristics, smoking history, diagnosis and reason for oxygen prescription), suggest that they were not much different from the rest of the group. Another important limitation of our study is that the patients receiving oxygen for palliative care such as “compassionate use” were not excluded. Palliative oxygen supplied to patients with terminal illnesses, generally cancer, should not be recorded under the same registry of LTOT as it is now.

Considering the local recommendations by health authorities, we expected that the LTOT prescription would be signed by pulmonologists. Nevertheless, we find that 29.3 % of the prescriptions are signed by internists. Previous studies show similar results [28]. LTOT is prescribed on the advice of internist and general practitioner in 20 and 27 %, respectively [16]. Katsenos and coworkers report that the prescriber for domiciliary oxygen therapy is a specialist in internal medicine in 8 % and cardiology in 2.8 % [21]. The recommendation to have LTOT signed by pulmonologists should be reinforced, as in our study, this was associated with more accurate prescriptions.

In conclusion, even considering all these limitations, we believe that our study provides an important insight into the poor adherence to the guidelines for LTOT. Considering the costs and the impact of LTOT on the patients’ quality of life, these data, albeit preliminary, suggest the need for more accurate prescription and monitoring of LTOT. The expected large savings in costs would provide resources to perform the necessary educational activities to improve and maintain the medical education of health professionals in charge of LTOT.