Abstract
BACKGROUND: The administration of a high FIO2 to COPD patients breathing spontaneously may result in hypercapnia, due to reversal of preexisting regional hypoxic pulmonary vasoconstriction, resulting in a greater dead space. Arterial blood gas trends have not been reported in these patients. In a 31-bed medical ICU in a teaching hospital we prospectively investigated the response of 17 CO2-retaining COPD patients, after acute respiratory crisis stabilization with noninvasive ventilation, to an FIO2 of 1.0 for 40 min, after having been noninvasively ventilated with an FIO2 of ≤ 0.50 for 40 min.
RESULTS: The mean ± SD baseline findings were: PaO2 101.4 ± 21.7 mm Hg, PaCO2 52.6 ± 10.4 mm Hg, breathing frequency 17.8 ± 3.7 breaths/min, tidal volume 601 ± 8 mL, and Glasgow coma score of 14.8 ± 0.3. PaO2 significantly increased (P < .001) when FIO2 was increased to 1.0, but there was no significant change in PaCO2, breathing frequency, tidal volume, or Glasgow coma score.
CONCLUSIONS: During noninvasive ventilation with an FIO2 sufficient to maintain a normal PaO2, a further increase in FIO2 did not increase PaCO2 in our CO2-retaining COPD patients.
Introduction
General principles guide the management of COPD patients presenting acutely to the ICU: treat precipitating factors (eg, infection); increase expiratory flow (eg, with β agonist); reduce pulmonary inflammation (eg, with corticosteroid); and manage gas exchange (eg, improve oxygenation).1 However, the administration of high FIO2 to these patients may result in hypercapnia.2–6 The reasons for this effect have been debated for many years: some believe there is a reduction in respiratory drive from the carotid chemoreceptors, and others think a worsened ventilation-perfusion matching is the cause.7
Noninvasive ventilation (NIV) benefits patients with COPD, and it seems reasonable to expect that NIV would increase tidal volume (VT) and improve CO2 elimination, and thus reduce respiratory drive.8 Published studies provide reasonable recommendations based on the effectiveness of NIV in COPD patients: reduction of treatment failure, lower mortality, fewer complications, and lower intubation rate, compared to conventional medical treatment.9 In these patients CO2 elimination is increased but overall ventilation-perfusion mismatch is not changed during NIV.10 A more important effect is the unloading of the respiratory muscles, which are often close to fatigue in severe episodes of respiratory failure.11 Crossley et al12 concluded that CO2-retaining COPD patients following a period of mechanical ventilation with PaO2 in the normal range can safely receive supplemental oxygen without retaining CO2 or a depression of respiratory drive. A new ventilation-perfusion relationship is established during ventilation to normoxia, and it is not altered by further increasing the FIO2. Nevertheless, the safety of oxygen supplementation during NIV in CO2-retaining COPD patients is not clear.
In CO2-retaining COPD patients recovering from acute respiratory crisis on NIV and an FIO2 of ≤ 0.5, we studied the response of PaCO2 to an FIO2 of 1.0.
QUICK LOOK
Current knowledge
High FIO2 in spontaneously breathing patients with COPD may result in hypercapnia, due to reversal of hypoxic pulmonary vasoconstriction, resulting in increased dead space.
What this paper contributes to our knowledge
During noninvasive ventilation with an FIO2 sufficient to maintain a normal PaO2, further FIO2 increases did not increase PaCO2 in spontaneously breathing patients with known carbon dioxide retention.
Methods
This study was approved by the ethics committee of Hospital Moinhos de Vento, Porto Alegre, Brazil. All subjects or the subject's legal representative gave written informed consent.
Subjects
We studied 17 COPD subjects admitted to our 31-bed medical ICU in a primary care hospital, who required NIV during treatment of acute respiratory failure (ARF). We excluded patients who were uncooperative or needed intubation. The subjects were all chronic CO2-retaining COPD patients, as defined by a resting PaCO2 of ≥ 45 mm Hg, previous hospital stay due to ARF-related COPD, and history of narcosis related to oxygen delivery. The diagnosis of COPD was based on history, physical examination, chest radiograph, and previous pulmonary function tests (if available). The subjects all received NIV (BiPAP Vision, Respironics, Murrysville, Pennsylvania) via oronasal mask (PerformaTrak, Respironics, Murrysville, Pennsylvania) for at least 24 hours, until stabilization of ARF.
Protocol
The high-FIO2 measurements were conducted only after stabilization of ARF, and in our clinical judgment there was no risk of needing intubation. Before the high-FIO2 measurements the noninvasive ventilator was calibrated with a gas flow analyzer (VT Plus-HF, Fluke Biomedical, Everett, Washington). Ventilator circuit leak was tested to calibrate the exhalation port (Whisper Swivel II, Respironics, Murrysville, Pennsylvania). The oronasal mask was positioned to permit a leak up to 20 L/min. The ventilator was set in the spontaneous/timed mode, with a PEEP of ≥ 5 cm H2O and a peak inspiratory pressure of ≥ 10 cm H2O, targeting and guarantying a VT or ≥ 8 mL/kg. The FIO2 was adjusted to maintain SpO2 of ≥ 90%.
We recorded age, sex, weight, primary disease process, and predicted risk of death based on admission Acute Physiology and Chronic Health Evaluation II score. The subjects had received nothing by mouth for at least 4 hours before the high-FIO2 measurements, were clinically stable, and remained on their usual treatment regimen. Baseline parameters for study purposes included VT, breathing frequency, the means of all cycles during minute volume (V̇E) measurement, arterial blood gas values (ABL 520, Radiometer, Copenhagen, Denmark), and SpO2 (66S, Hewlett Packard, Palo Alto, California).
The high-FIO2 period involved only increasing the FIO2 to 1.0: no other parameters were altered. Following 40 min at an FIO2 of 1.0 we again measured VT, breathing frequency, V̇E, arterial blood gases, SpO2, and Glasgow coma score. FIO2 was then returned to its previous value. The subjects were not made aware of the FIO2 changes.
Statistical Analysis
Continuous variables are expressed as mean ± SD. Differences between baseline and high-FIO2 were analyzed with the paired t test, except for Glasgow coma score, which we analyzed with the Wilcoxon signed-rank test. All statistical analysis was performed by a statistician using statistics software (SPSS 16.0, SPSS, Chicago, Illinois). Statistical significance was set at P < .05.
Results
Among the 17 subjects, 9 were admitted due to pneumonia, and 8 were admitted due to COPD exacerbation (Table 1). No subjects were withdrawn after enrollment. Before the high-FIO2 measurements all the subjects were on NIV and receiving an FIO2 between 0.25 and 0.5.
Subject Characteristics at Study Admission
The FIO2 increase significantly increased the mean PaO2, from 101.4 ± 21.7 mm Hg to 290.5 ± 35.7 mm Hg (P < .001) and the mean SpO2, from 94.3 ± 2.2% to 98.8 ± 0.8% (P < .001). There were no significant changes in any of the other measurements (Table 2). The mean baseline PaCO2 was 52.5 ± 10.4 mm Hg, and the mean high-FIO2 was 51.5 ± 12.3 mm Hg. We think that a PaCO2 increase of 5 mm Hg is the minimum clinically important change. The standard deviation of the difference between the PaCO2 recordings at the 2 different FIO2 levels was 4 mm Hg. For a paired sample of 17 patients, this study has a power of 99%.
Respiratory Data Before and After FIO2 of 1.0
Discussion
Our results support the hypothesis that increasing the FIO2 in CO2-retaining COPD subjects on NIV does not cause any clinically important change in CO2 retention.
A COPD exacerbation is defined as worsening dyspnea, cough, and/or sputum production.13 Expiratory air-flow obstruction is worsened, the work of breathing increases, and mucus production or mucociliary clearance, or both, are altered. Spirometry shows worsened expiratory air-flow obstruction, and arterial blood gas analysis usually shows an additional decrease in PaO2, which leads to pulmonary arterial vasoconstriction and pulmonary hypertension.14
Supplemental oxygen is the most useful treatment in COPD-induced hypercapnic ARF, and oxygen is administered to all hypoxemic COPD patients during exacerbation. Oxygen decreases anaerobic metabolism and lactic acid production; improves brain function; decrease arrhythmias, ischemia, and pulmonary hypertension; improves right-heart function; decreases the release of antidiuretic hormone; increases the kidneys' ability to clear free water; decreases the formation of extravascular lung water (ie, pulmonary edema); improves survival; and decreases red blood cell mass and hematocrit.14,15
The PaCO2 commonly rises somewhat when a patient with COPD receives supplemental oxygen,16 but carbon dioxide narcosis due to oxygen therapy is uncommon, and patients should not be kept hypoxemic for fear that oxygen therapy could aggravate carbon dioxide retention.17 The increase in CO2 is probably due to a change in dead space or shift of the hemoglobin-oxygen binding curve, rather than decreased respiratory drive.18 This expected rise should not be specifically treated unless it is excessive, resulting in a trend toward acute respiratory acidosis on serial arterial blood gas analyses, with central nervous system or cardiovascular side effects. Carbon dioxide narcosis may occur with excessive FIO2, but is much less likely with low-flow, controlled oxygen therapy.14
Other authors have studied the behavior of PaCO2 during increases of FIO2 in spontaneously breathing19–23 and mechanically ventilated COPD patients,12 but PaCO2 behavior during NIV has not previously been investigated. Sassoon et al,19 in 17 stable COPD patients found that when the mean FIO2 was increased to 0.94 the mean PaCO2 increased significantly, by 4.4 mm Hg, primarily due to a 4% increase in dead space. They concluded that hyperoxia-induced hypercapnia is primarily due to impairment of gas exchange rather than to depression of ventilation.
Aubier et al20 treated 20 COPD patients in ARF with oxygen at 5 L/min for 30 min, and measured arterial blood gases before and at the end of oxygen administration. They found only a small rise in PaCO2 (from 61 mm Hg to 68 mm Hg), despite a large rise in PaO2. Although PaCO2 rose in all the subjects, and V̇E fell slightly (14%), there was no correlation between the rise in PaCO2 and the fall in ventilation, which suggests that the rise is not predominantly the result of a decrease in ventilation.
In another study,21 the same group studied the effects of 100% oxygen on V̇E and arterial blood gases in COPD patients in ARF, and concluded that, despite removal of the hypoxic stimulus, the activity of the respiratory muscles maintained the V̇E at nearly the same value as that while breathing room air. Again, there was no correlation between PaCO2 and V̇E. These data led those authors to conclude that, during ARF, although there is an initial decrease in ventilation resulting from loss of hypoxic drive, the rise in PaCO2 following correction of hypoxia is not primarily caused by decreased ventilation.
In our patients the NIV guaranteed VT and did not permit changes in V̇E (10.7 ± 2.4 L/min vs 10.7 ± 2.6 L/min, P = .96). In agreement, Hanson et al24 and Dick et al25 concluded that changes in physiologic dead space are sufficient to account for the hypercapnia.
Scano et al22 studied stable COPD patients and found that respiratory drive in response to CO2 is similar in hypercapnic COPD patients to that in normal volunteers, although less than in normocapnic COPD patients. Robinson et al26 used the multiple inert gas elimination technique to measure ventilation, cardiac output, and the distribution of ventilation-perfusion ratio in patients with a COPD exacerbation. They found that in patients in whom PaCO2 rises in response to 100% oxygen, ventilation decreases and alveolar dead space increases. In our study the only significant changes during high FIO2 were increased PaO2 and SpO2. There was no evidence of depression of respiratory drive due to high FIO2, since Glasgow coma score, VT, breathing frequency, pH, PaCO2, and V̇E were unchanged.
In patients who remained hypoxemic and/or in respiratory distress despite standard medical therapy (including oxygen), NIV has successfully supported gas exchange and prevented intubation. By counterbalancing intrinsic PEEP with applied PEEP, and by augmenting VT, NIV reduces the work of breathing and averts the circle leading to ARF.27 NIV improves vital signs, gas exchange, and dyspnea; may obviate intubation; reduces morbidity and mortality; and shortens hospital stay in patients with moderate to severe COPD exacerbation.9,11 A recent meta-analysis28 found that, compared with standard therapy, NIV reduced the need for intubation by 65% (95% CI 0.26–0.47%), decreased in-hospital mortality by 55% (95% CI 0.30–0.66%), and shortened hospitalization by 1.9 days (95% CI 0.0–3.9). Thus, NIV is considered the ventilation mode of choice in hypercapnic patients with exacerbations of COPD.
Our study strengths include that it was a bedside clinical study, and the sample size calculation. Since the ventilator measurements were from a digital readout and blood gas results printed from a machine, we feel there was little chance of bias on the part of the data collectors. Our study limitations were that dead space was not measured, the sample size was small, the study was not randomized, but, since it was a physiologic study, we supposed that randomization was not needed.
Conclusions
During NIV with an FIO2 sufficient to maintain a normal PaO2, a further increase in FIO2 does not result in an increased PaCO2 in CO2-retaining COPD patients, since no changes occur in V̇E.
Footnotes
- Correspondence: Cassiano Teixeira MD PhD, Intensive Care Unit, Moinhos de Vento Hospital, Rua Ramiro Barcelos 910, Porto Alegre, Rio Grande do Sul, Brazil 90035–001. E-mail: cassiano.rush{at}gmail.com.br.
The authors have disclosed no conflicts of interest.
- Copyright © 2014 by Daedalus Enterprises
