QJM Advance Access originally published online on June 13, 2005
QJM 2005 98(7):499-504; doi:10.1093/qjmed/hci084
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Initial oxygen management in patients with an exacerbation of chronic obstructive pulmonary disease
From the Department of Respiratory Medicine, Norfolk and Norwich University Hospital, Norwich, Norfolk, UK
Address correspondence to Dr H.J. Durrington, Division of Respiratory Medicine, Department of Medicine, Box 157, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ. email: hannahd{at}doctors.org.uk
Received 25 January 2005 and in revised form 11 April 2005
 |
Summary |
|---|
 Top Summary IntroductionMethodsResultsDiscussionReferences |
|---|
Background: The Norfolk and Norwich University Hospital (NNUH) is situated in rural Norfolk, and ambulance journey times are often >30 min. Longer ambulance journeys could lead to a greater risk of hypercapnia, if inappropriately high concentrations of oxygen are given during an exacerbation of COPD.
Aim: To investigate the effect of high concentration oxygen (HCO, FiO2 > 0.28) on COPD patients, and the outcome of instituting a simple protocol to reduce such exposure.
Design: Retrospective audit.
Method: An audit was conducted of all patients admitted with an exacerbation of COPD to the NNUH during the 2 months from 1 December 2001 to 31 January 2002 (n = 108). Results were shared with paramedics, and guidelines agreed for the initial provision of lower concentrations of oxygen (LCO, FiO2 
0.28). A second audit was conducted a year later between 1 December 2002 and 31 January 2003 (n = 103).
Results: HCO caused significant (p < 0.01) acidosis and inappropriately high PaO2 and PaCO2, compared to initial LCO therapy. There was a significantly increased complication rate during admission (p < 0.01) in those COPD patients receiving HCO compared to LCO, particularly when ambulance journeys exceeded 30 min. The second audit demonstrated a significant (p < 0.001) reduction in the number of patients initially receiving HCO, but the complication rate was unaltered.
Discussion: A simple intervention, such as providing paramedics with 28% Venturi masks, can reduce the number of COPD patients exposed to HCO. A randomized controlled trial is long overdue to establish whether HCO or LCO as initial management is associated with the most favourable prognosis in different hospital settings.
|
Introduction |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Over 50 years ago, CO2 narcosis and acidosis was described in patients with exacerbations of chronic obstructive pulmonary disease (COPD).1 That hypercapnia in such patients could be secondary to oxygen administration was confirmed in subsequent reports.2,3 Oxygen-induced hypercapnia results from a reduction in the hypoxic drive to ventilation when oxygen is administered to patients with some pre-existing chronic hypercapnia whose sensitivity to CO2 is suppressed (by an uncertain mechanism). Oxygen-induced respiratory acidosis in COPD leading to a pH<7.3 is associated with an increased risk of intensive care admission.4 The reduction in pH is inversely correlated with arterial oxygen tension, and can be ameliorated by limiting the inspired oxygen concentration. This, however, could expose patients to the complications of more severe hypoxaemia. Although some adaptation to hypoxia can occur in patients with COPD,5 Hutchinson and coworkers6 have suggested that a PaO2 of 50 mmHg (6.5 kPa) is necessary to prevent immediate death from hypoxia, and that oxygen therapy should provide a PaO2 of at least this level.
Patients with hypercapnic respiratory failure are very sensitive to small increments in the concentration of inspired oxygen,7,8 and even a concentration of 25% generally produces considerable relief from hypoxia, an effect related to the oxygen dissociation curve, where small changes of PaO2 (from 25 to 40 mmHg) produce large changes in oxygen saturation.9 British Thoracic Society (BTS) guidelines published in 199710 recommended that in exacerbations of COPD, initial oxygen management should be with 24–28% Venturi masks or 2 l/min via nasal prongs, followed by measurement of arterial blood gases after 60 min.
NICE guidelines were published in 2004.11 These suggest that oxygen therapy be commenced at 40% during transfer to hospital, titrated upwards if saturation falls below 90% and downwards if the patient becomes drowsy or if the saturation exceeds 93–94%. On arrival to hospital, arterial blood gases should be measured and the inspired oxygen concentration noted in all patients with an exacerbation of COPD. Interestingly, NICE found only five reports2,12–15 additional to that of Plant et al.,4 each including only 19–35 patients, indicating that oxygen therapy may lead to hypercapnia and acidosis. Evidence that a 40% fraction of inspired oxygen (FiO2), as opposed to 24% or 28%, should be the initial management was not found, and the recommendation was based on ‘opinion and clinical experiences of respected authorities’, which seems an extraordinary state of affairs for one of the most common medical emergencies requiring hospital admission. An earlier systematic review had also drawn attention to the same lack of evidence that low concentration oxygen results in fewer deaths from CO2 narcosis, or more from hypoxia.16 While the recommendations of the North West Oxygen Group17 (based on this report16) were similar to the later NICE guidance, it was emphasized that in rural areas, where ambulance journeys to hospital were on average longer than the typical 15 min or less in conurbations, less liberal oxygen management, similar to the earlier BTS advice,10 may be more appropriate.
The present study was done at the Norfolk and Norwich University Hospital, which has a substantially rural catchment area. Before the investigation, no local guidelines existed for the emergency services, including ambulance crews, and oxygen was administered liberally. We investigated the effects on the incidence of hypercapnia and acidosis of limiting the administration of oxygen concentration in excess of 28%. We also explored various clinical considerations and end-points which would be important in the design of a multicentre randomized trial.
|
Methods |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Study participants
All patients with COPD admitted to Norfolk and Norwich University Hospital as emergencies by ambulance during the two months from 1 December 2001 to 31 January 2002, and during the 2 months from 1 December 2002 to 31 January 2003 were studied using the same procedure. The patients included in this study were identified as having COPD retrospectively from the coded discharge summaries and case notes, using NICE criteria, by two of us (HJD and MF).11 Information was also taken from the ambulance service forms completed by the crews at the scene of the emergency, GP admission letters, medical admission unit documentation and accident and emergency assessment forms. The ambulance crew's decision was regarded as critical for initial emergency oxygen therapy. Although during both study periods the crews monitored oxygen saturation using pulse oximetry, they did not receive detailed advice as to how to use this information in determining the appropriate concentration of inspired oxygen until the second study period. Prior to this, it was decided that all patients known to have a diagnosis of COPD should be given controlled oxygen via a 28% Venturi mask during the ambulance transfer in order to keep their oxygen saturations between 88–92%. If the oxygen saturation fell below 88%, then a higher fraction of inspired oxygen (FiO2 > 0.28) could be given. To assist the ambulance crews in diagnosing COPD, some patients were given plastic cards following a previous admission.
Arterial blood gases (pH, PaCO2 and PaO2) were measured in the hospital Clinical Chemistry Department as soon as possible after an immediate assessment had been made by the Accident and Emergency staff. The inspired oxygen concentrations employed by the ambulance crews and that adopted on arrival in hospital prior to blood gas determination were recorded. The investigation was approved by the hospital's audit review board as part of its clinical audit programme. The results of the initial 2 months' study were presented to the local ambulance crews and strategies aimed at improving initial oxygen treatment mutually adopted. A second audit study was done a year later.
An admission was considered as complicated if it resulted in death from any cause in hospital (despite this, the cause of death in every fatal case was recorded on the death certificate as COPD) or if intravenous aminophylline or ventilation, either non-invasive or invasive (admission to intensive therapy unit), was required. The use of intravenous aminophylline was considered to indicate a severe exacerbation of COPD, because it was given according to the NICE guidelines11 only after the standard treatment regimen of nebulized bronchodilators, steroids and antibiotics produced inadequate improvement.
Statistical analysis
Results for continuously distributed variables are presented as means (95%CIs) and categorical variables as percentages (95%CIs). Results were considered to be significantly different if CIs did not overlap. The level of statistical significance was determined using Student's t test for continuous variables and the 
2 test for categorical variables. Where data were incomplete, statistical tests and descriptors were based on the number of patients for whom results were available, and this is noted in the text.
|
Results |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
In the first 2-month study period, there were 108 acute admissions with COPD (57% male) mean age 73 years (range 44–98 years), and during the second study period one year later there were 103 acute admissions with COPD (56% male), mean age 72 (range 47–91) years. We did not exclude two patients who were re-admitted within the first study period. Previously recorded spirometry measurements at the end of earlier admissions or at an out-patient attendance revealed a mean FEV1 of 0.96 l (95%CI 0.74–1.19) for the first study group (n = 71) and 0.80 l (0.60–1.00) for the second group (n = 62). Comparison was also made of previously recorded interval arterial blood gas results. Again, no significant differences between the two groups were apparent, mean (95%CI) pH being 7.40 (7.38–7.42) in the first group and 7.40 (7.39–7.41) in the second. Mean PaO2 was 9.40 (8.41–10.39) kPa in the first group and 8.70 (8.15–9.25) kPa in the second. Mean PaCO2 was 5.80 (5.46–6.14) kPa in the first and 6.00 (5.60–6.40) kPa in the second. Some 17.6% (10.4–24.8) of the first group and 11.7% (5.49–17.9) of the second group were receiving home oxygen (either long term or intermittently). Ambulance journey times were similar, being 33 min (range 7–90) in the first study and 30 min (7–73) in the second. The ambulance crew made a correct diagnosis of an exacerbation of COPD in 58% cases overall during both periods, with no statistically significant improvement during the second audit period. The commonest reason for an incorrect diagnosis was lack of precision: the crews, for example, simply recording ‘increasing shortness of breath’ in 29% of cases.
Patients receiving a high inspired oxygen concentration at the time that their arterial blood gases were measured were significantly more acidotic and had higher PaCO2 and higher PaO2 values than those who had received low inspired oxygen concentrations throughout, or who had been converted from high to low inspired oxygen on arrival at the hospital (all p < 0.01) (Table 1).
|
In both study periods, there was a clear trend for the likelihood that an admission would be complicated to be associated with increasing exposure to high inspired oxygen concentration (Table 1). When data from both study periods were combined, 25.2% (20.9–29.5) of those receiving low inspired oxygen throughout had complicated admissions compared to 40.8% (33.8–47.8) of those exposed to high oxygen in the ambulance and then converted to low concentration on arrival in hospital (p < 0.05) and 64.7 (53.1–76.3)% of those receiving high inspired oxygen throughout (p < 0.05). The influence of initial oxygen administration on the components of our composite end-point is shown in Figure 1.
|
The complication rate in those whose ambulance time was <30 min was 25.9% (14.6–37.2) (n = 58) and in those for whom it was
30 minutes it was 46.0% (33.7–58) (n = 63). This difference did not by itself achieve statistical significance. The combination of longer ambulance journeys and the administration of high concentrations of inspired oxygen, however, was clearly associated with the worst outcome. Thus complications ensued in only 19.4% (12.3–26.5) of those whose ambulance journey was <30 min and who received only low concentrations of inspired oxygen, whereas the rate of complications was 60.0% (51.1–68.9) in those whose journey was 30 min or more, and who were treated with high oxygen in the ambulance (p < 0.05). The likelihood of receiving high-concentration inspired oxygen was similar, regardless of the ambulance journey time (n = 121). In 2002/3, the proportion of patients receiving low concentration of oxygen in the ambulance, as opposed to higher concentrations, was increased from 51 to 75% (p < 0.05) (Table 1). In only one of the patients who received a high inspired oxygen concentration in the ambulance, was this maintained after arrival in hospital in 2002/3, whereas it was in 17% in 2001/2. The overall proportion of complicated admissions, regardless of initial oxygen therapy, did not change significantly between the two study periods, being 35% in 2001/2 and 33% in 2002/3. Mortality was 16/108 (14.8%) in the first study period and 14/103 (13.6%) in the second.
|
Discussion |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Consistent with earlier reports,4,12–15 our patients with an exacerbation of COPD who received high concentration oxygen became significantly acidotic and developed inappropriately high PaO2 and PaCO2 levels. This acidosis could be corrected fully by reducing the inspired oxygen concentration in the casualty department. However, despite this, those COPD patients who received high concentration oxygen therapy at any time (even if the oxygen concentration was reduced on admission to casualty) developed significantly more complications during admission compared to those patients who received low concentration oxygen throughout. We successfully reduced the number of patients with an exacerbation of COPD who received high concentration oxygen in the ambulance. This was likely to have occurred because of a mutually agreed change in the practice of ambulance crews after the first study, because it could not be explained by a greater frequency of cases of COPD with less severe underlying disease being admitted in the second study period; results of interval spirometry and arterial blood gases and the proportion receiving home oxygen in both periods being similar. It is ironic that although oxygen is the most widely administered therapy in respiratory emergencies, randomized placebo controlled trials to establish either its benefit or its disadvantages do not exist. Because hypoxaemia can be rapidly and demonstrably improved with oxygen administration, in most situations it may be considered that such evidence is unnecessary. However, it is also well established that in states of chronic hypoxaemia, of which COPD is the most frequently encountered in emergency medical practice, even partial correction of hypoxaemia may lead to hypercapnia with serious, even fatal, adverse consequences.4
The development of hypercapnia can be recognized early and averted in hospital by monitoring arterial blood gases and regulating the delivery of oxygen according to the arterial PaCO2 response.6–15 The difficulty for those providing emergency services outside of the hospital is how to recognize patients who might be adversely affected by the administration of high concentration oxygen. In a cyanosed, severely dyspnoeic patients, it is extremely hard to resist the temptation to give such treatment not only for symptomatic relief, but also to relieve the anxiety of the medical attendant. Those writing guidelines for the immediate management of COPD are also appropriately concerned that adequate oxygen therapy might be withheld from patients with COPD who could benefit, and that patients with other acute respiratory conditions might not receive sufficient oxygen, if the initial diagnosis of COPD was incorrect or if guidelines led to the mistaken belief that such treatment was generally harmful.6 Our study would entirely support the view that a relatively high proportion of cases of COPD are misdiagnosed by general practitioners and ambulance crews. A system to assist them in making a more accurate diagnosis of COPD would thus be desirable.17 Issuing plastic cards with the information that the patient had COPD, did not in our study lead to an improvement in diagnostic accuracy, perhaps because the card was lost or left behind at home. Further work in this area is needed with, for example, greater reinforcement of the advice to carry the card or the adoption of another system such as bracelet or even a central register available to ambulance control. Such a register could be compiled not only from details of previous acute admissions with COPD, but also from outpatient attendances and increasingly from improved identification of patients in general practice.
In our study there was no statistically significant evidence in terms of the overall complication rate of either an adverse effect of reducing the concentration of inspired oxygen during the ambulance journey nor of a favourable effect of diminishing the incidence of acidosis and hypercarpnia. The latter might have been anticipated, because of the statistically significant association between exposure to high concentration oxygen and complication rate. There are several possible explanations for this. One is that the development of acidosis and hypercapnia on high concentration oxygen is simply a reflection of the severity of underlying disease which is the true determinant of prognosis. Another, perhaps more likely explanation, is that a much larger study than ours would be required to detect a significant reduction in complications given the variability of the patient population and hospital medical practice and the confounding effects of factors such as journey times.
Some guidelines, typified by those of NICE, have considered that high concentration of oxygen should be administered to all respiratory emergencies before arrival in hospital, if this is for a relatively brief period, because exposure of COPD patients to any hypercapnia it produces will be brief and unlikely to counteract the benefit of oxygen therapy in the majority of respiratory emergencies. This may be true when ambulance journey times are short, the ambulance crews do not spend long at the scene ‘stabilizing’ the patient, or when the patient is seen promptly by nursing and medical staff on arrival at hospital, and the appropriateness of high concentration oxygen therapy reassessed, including the measurement of arterial blood gases and pH. We found that the worst prognosis was associated with the combination of a long journey time to hospital and the administration of high concentration oxygen. This argues that length of exposure of COPD patients to high oxygen is causally related to complication rate, unless those with more severe underlying disease lived further away from the hospital, which seems improbable. It may also explain why clinical experience of the administration of high concentration oxygen by ambulance crews in urban areas with a high population density and short journey times may be different from ours, leading to the NICE guidance.
A large, randomized, placebo-controlled trial is required to investigate the optimal use of oxygen therapy in acute exacerbations of COPD and to provide improved guidelines for emergency services. Patients could ethically be randomized to either 28% or 40% initial FiO2, because both are in current use. Our study suggests a possible, simple, composite clinical outcome measure, such as the one we used. The trials should ideally be multicentre, including hospitals in both urban and rural settings, to allow the effect of ambulance journey times on optimal oxygen treatment to be assessed. Our results suggest that greater diagnostic accuracy could be achieved if ambulance crews were provided with information from a central registry linked to the ambulance control centre when they radioed in from the home of a patient with suspected COPD. Randomization could be undertaken at the same time.
|
Acknowledgments |
|---|
We thank Dr J. Scott and all the paramedical, ambulance and Accident and Emergency staff who contributed to this investigation. We are also indebted to Dr A. Davison, the inventor of the plastic credit card system as a way of identifying patients with COPD.
|
References |
|---|
|
TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
1. Donald KW. Neurological effects of oxygen. Lancet 1949; ii:1056–7.
2. Westlake EK, Simpson T, Kaye, M. Carbon dioxide narcosis in emphysema. Q J Med 1955; 94:155–73.
3. McNichol MW, Campbell EJM. Severity of respiratory failure. Lancet 1965; i:336–8.
4. Plant PK, Owen JL, Elliot MW. One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: Implications for the provision of NIV and oxygen administration. Thorax 2000; 55:550–4.
5. Mithoefer JC, Karestsky MS, Mead GD. Oxygen therapy in respiratory failure. N Engl J Med 1967; 277:947–9.[Medline]
6. Hutchison DCS, Fenley DC, Donald KW. Controlled oxygen therapy in respiratory failure. Br Med J 1964; 2:1159–66.
7. Campbell EJM. The relation between oxygen concentrations of inspired air and arterial blood. Lancet 1960; ii:10–11.
8. Campbell EJM. A method of controlled oxygen administration which reduces the risk of carbon-dioxide retention. Lancet 1960; ii:12–14.[CrossRef]
9. Campbell EJM. The management of acute respiratory failure in chronic bronchitis and emphysema. Am Rev Resp Dis 1967; 96:626–39.[Web of Science][Medline]
10. British Thoracic Society. Guidelines for the management of acute exacerbations of COPD. Thorax 1997; 52 (Suppl 5):S16–21.
11. National Institute for Clinical Excellence (NICE). Chronic obstructive pulmonary disease: National clinical guidelines for management of chronic obstructive pulmonary disease in adults in primary and secondary care. Thorax 2004; 59 (Suppl. 1):1–232.[Medline]
12. Smithy JP, Stone RW, Muschenheim C. Acute respiratory failure in chronic lung disease. Am Rev Respir Dis 1968; 97:791–803.[Medline]
13. Eldridge F, Gherman C. Studies of oxygen administration in respiratory failure. Ann Intern Med 1968; 68:567–78.
14. Aubier M, Murciano D, Milic-Emili J, Touaty E, Daghfous J, Pariente R, et al. Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure. Am Rev Respir Dis 1980; 122:747–54.[Web of Science][Medline]
15. DeGaute JP, Domenighetti G, Naeije R, Vincent JL, Treyvaud D, Perret C. Oxygen delivery in acute exacerbation of chronic obstructive pulmonary disease. Effects of controlled oxygen therapy. Am Rev Respir Dis 1981; 124:26–30.[Medline]
16. Murphy R, Driscoll P, O'Driscoll R. Emergency oxygen therapy for the COPD patient. Emerg Med J 2001; 18:333–9.
17. Murphy R, Mackway-Jones K, Sammy I, Driscoll P, Gray A, O'Driscoll R, O'Reilly J, Niven R, Bentley A, Brear G, Kishen R. Emergency oxygen therapy for the breathless patient. Guidelines prepared by North West Oxygen Group. Emerg Med J 2001; 18:421–3.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Wijesinghe, P. Shirtcliffe, K. Perrin, B. Healy, K. James, M. Weatherall, and R. Beasley An audit of the effect of oxygen prescription charts on clinical practice Postgrad. Med. J., February 1, 2010; 86(1012): 89 - 93. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||