Titrated oxygen regimens require two components: titrated supplemental oxygen to achieve a particular target arterial oxygen saturation measured by pulse oximetry SpO 2 , and bronchodilators delivered by either air-driven nebulisation or metered-dose inhalers with a spacer. Oxygen-driven nebulisation inadvertently exposes patients to high concentrations of inspired oxygen, particularly with prolonged or repeated use as may occur in patients with severe exacerbations during long pre-hospital transfers or if the mask is inadvertently left in place.
We have shown that air-driven bronchodilator nebulisation prevents the increase in arterial partial pressure of carbon dioxide PaCO 2 that results from use of oxygen-driven nebulisers in patients with stable COPD [ 3 ]. However, there are only two small non-blinded randomised controlled trials of air compared to oxygen-driven nebulisation in patients admitted to hospital with AECOPD [ 4 , 5 ]. These trials reported that administration of a single bronchodilator dose using oxygen-driven nebulisation increases the PaCO 2 in COPD patients who have baseline hypercapnia.
Robust determination of the risks of oxygen-driven nebulisation in AECOPD could identify whether widespread implementation of air-driven nebulisers, or use of metered-dose inhalers through a spacer, are required to ensure safe delivery of bronchodilators to this high-risk patient group.
Our hypothesis was that two doses of oxygen-driven bronchodilator nebulisation would increase the PaCO 2 compared with air-driven nebulisation in patients hospitalised with an AECOPD. This was a parallel-group double-blind randomised controlled trial at Wellington Regional Hospital, New Zealand. The full study protocol is available in the online supplement.
Written informed consent was obtained before any study-specific procedures. The study was undertaken on the ward during the hospital admission. The full study protocol original and updated version can be found on the OLS see Additional file 1 and 2. Randomisation was by a block randomised computer generated sequence block size six , provided in sealed opaque envelopes by the study statistician who was independent of recruitment and assessment of participants.
The participants and blinded investigator, who recorded heart rate and PtCO 2 were masked to the randomised treatments. If both oxygen and air ports were available in hospital on the wall behind the participant, these were used for driving nebulisation. Both the participant and blinded investigator faced forward for the full duration of the study. Likewise, the blinded investigator and patient could not view the SpO 2 on the Sentec device, as this was covered during the interventions, or the pulse oximeter which could only be viewed by the unblinded investigator.
Randomisation was performed after the 15 min wash-in period, when both patient and blinded investigator were already in a forward-facing position to maintain blinding.
The unblinded investigator recorded SpO 2 on a separate pulse-oximeter from then onwards. Immediately before the first nebulisation, denoted by the baseline reading at time-point zero, PtCO 2 , SpO 2 and heart rate were recorded. Participants then received two administrations of 2. The nebulisations were delivered by the unblinded investigator at time zero and at 20 min, allowing for a five minute interval between nebulisations.
Recordings were continued for 45 min after completion of the last nebulisation 80 min after baseline. Immediately before the first nebulisation and just before completion of the second nebulisation, at 35 min, a capillary blood gas sample was taken from the fingertip for measurement of PcapCO 2 and pH.
Participants in the air-driven group who were receiving oxygen at the start of nebulisation continued to receive titrated supplemental oxygen via nasal prongs underneath the nebuliser mask. Those in the oxygen-driven group had the prongs removed at the start, and reapplied after the completion of each nebulisation. At 35 min, oxygen was delivered via nasal prongs to participants at the flow rate they last received during titration i.
The primary outcome was originally planned to be PcapCO 2 at 35 min, at completion of the second nebulisation. However, after the first 14 participants had been studied, it was evident that obtaining adequate amounts of blood to fill the capillary tubes from some participants was difficult.
The primary outcome variable was therefore changed to PtCO 2 at 35 min, with PcapCO 2 at 35 min reverting to a secondary outcome variable. A power exponential in time correlation structure was used for the repeated measurements. The secondary outcome variables of PtCO 2 at the other time points, SpO 2 and heart rate used similar mixed linear models. PcapCO 2 and pH were compared by Analysis of Covariance with the baseline measurement as a continuous co-variate. As a post-hoc analysis we compared the difference in PtCO 2 between the 15 and 6 min, and the 35 and 26 min time points.
The time for PtCO 2 to return to baseline during the observation period defined as the time until the PtCO 2 was first equal to or below the baseline value, between 40 and 80 min , was compared using Kaplan-Meier survival curves and a Cox Proportional Hazards model. A simple t-test was used to compare the lowest value of the SpO 2 between 40 and 80 min, compared to baseline. SAS version 9.
The trial recruited between May 14th and June 29th One participant withdrew after 18 min of air-driven nebulisation because of feeling flushed, and so complete data was available for PtCO 2 for 89 participants.
The baseline PtCO 2 for this participant was This participant had study measurements continued after this for the full duration of the study.
No clinical adverse events were noted during the intervention periods. A summary of baseline participant characteristics are shown in Table 1. Participants predominantly had severe airflow obstruction with a mean FEV 1 of The mean range baseline PtCO 2 was Patients randomised to the oxygen group were more likely to have required assisted ventilation previously.
Previous guidelines also recommended the immediate administration of O 2 to patients with diagnosed or suspected ACS, without any respect to the blood O 2 saturation [ 7 , 8 , 9 , 10 ]. The history of O 2 as a medicine dates back to when the British chemist Joseph Priestly discovered O 2 and stated that it could be used as a medicine [ 11 ].
It was, however, in that the first publication on the role of O 2 therapy in patients with chest pain was published. It was a short letter by Dr. Charles Steele, in which he deemed that O 2 therapy had relieved chest pains in one single patient he believed to have angina [ 12 ].
Ever since this letter by Dr. Steele, several studies have tried to answer how supplemental O 2 therapy in both healthy and ill patients affect their cardiovascular system. Studies on canines [ 14 , 15 , 16 ] have given some support to this theory, showing that O 2 therapy decreases infarct size and ischemia in these animals. A recent study on swine, however, showed that hyperoxemia can aggravate and worsen myocardial ischemia [ 17 ].
In healthy individuals, experimental studies have shown that hyperoxemia because of supplemental O 2 therapy, may contribute to negative cardiovascular effects like a decrease in coronary blood flow, arterial vasoconstriction, diminished cardiac output, an increase in the systemic vascular resistance as well as impaired blood flow to organs and tissues [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].
In patients with suspected as well as confirmed myocardial infarction, the role of O 2 were for a long time highly inconclusive. Our knowledge gap in this matter was not because of lack of studies, but rather because of the poor methodologies used in these studies. Ever since , several studies have been published on the role of O 2 in patients with chest pain, coronary artery disease, cardiac failure as well as suspected and confirmed myocardial infarction.
All of them have unfortunately had serious limitations and have therefore not been able to correctly answer the question of how O 2 therapy affects the cardiovascular system in both healthy patients and patients with myocardial infarction and cardiac failure. The studies have either been case studies or small reports including only a few patients, thus not being generalizable, or small studies [ 18 , 19 , 20 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ].
Furthermore, the vast majority of the studies was conducted in the pre-PCI era and even before Troponin was used as an important part in the diagnosis of myocardial infarction. Because of the above limitations, a Cochrane report from [ 44 ] called for randomized controlled trials to once for all answer the question about which role supplemental O 2 therapy should have in patients with chest pain and suspected myocardial infarction.
Before the Cochrane reports call for a definitive randomized controlled trial RCT in , there were already four RCTs on the role of supplemental O 2 in patients with myocardial infarction; Rawles et al. The two first studies were conducted in the pre-PCI era. While Wilson et al. The study by Ukholkina et al. The study is thus highly biased because of a limited methodology [ 44 ].
Rancord et al. The authors found no significant differences between the two arms supplemental O 2 vs titrated O 2 with regard to infarct size as measured by cardiac Troponin T, as well as cardiac MRI CMRI close to one month after inclusion. Even though the study found no significant difference in infarct size as measured by cardiac Troponin, a subset of the patients undergoing CMRI after six months, showed that those randomized to supplemental O 2 therapy, had a larger infarct size as measured in absolute mass but not in percent of the left ventricle.
A sub study [ 49 ] of the AVOID trial showed later that patients randomized to the O 2 arm, had significantly higher cardiac Troponin rates than those randomized to the air arm.
Patients were randomized to either supplemental O 2 therapy or air. All patients underwent CMRI, while only a subset of patients underwent echocardiography. Ninety-four patients underwent CMRI which showed no significant difference between the two arms in discussing infarct size, myocardium at risk and myocardial salvage index [ 51 ].
Of the 87 patients undergoing echocardiography, no significant differences could be measured between the two arms in discussing left ventricular ejection fraction and wall motion score index [ 52 ]. In a recently published sub study, patients were assessed in regard to chest pain to evaluate the analgesic effect of O 2 therapy.
Those randomized to the supplemental O 2 group had significantly higher median VAS and also received significantly higher amounts of morphine. The study could not show that supplemental O 2 diminished chest pain [ 53 ]. The main publication by Hofmann et al. The study found no significant differences between the two arms in regard to mortality nor morbidity [ 55 ].
Table 1 summarizes all the RCTs. The above RCTs clearly show that O 2 therapy has so positive nor negative cardiovascular effects, when used in normoxic patients with STEMI both prehospital and in-hospital. Two recent reviews and meta-analysis on the role of supplemental O 2 therapy in acute myocardial infarction, showed also no benefit of using O 2 therapy in these patients [ 58 , 59 ]. In discussing supplemental O 2 therapy in normoxic STEMI patients, the evidences are clear and consistent, why all guidelines must be reformed to state that supplemental O 2 therapy in these patients should be omitted.
It is, however, of high importance to point that patients diagnosed with STEMI, and who have a low blood oxygen saturation, should receive supplemental O 2. It is the routine use of O 2 therapy, with no respect to blood oxygen saturation, that should be omitted Fig.
With this said, it is important to point out that the RCTs presented above does also have some limitations as the majority of them have had a small cohort, and the focus have been stable and normoxic STEMI patients. These limitations might reduce the generalizability of the studies. This is especiCally of importance since some studies argue that supplemental O 2 therapy administrated to acutely ill patients can be toxic and increase mortality and morbidity [ 60 , 61 ].
Fourth universal definition of myocardial infarction Eur Heart J. At high flow rates, it can provide continuous positive airway pressure CPAP , washes out CO 2 from the respiratory dead space, and assists the process of oxygen diffusion into the alveoli replacing oxygen which has been absorbed.
Depending on the physiology of the patient, HFNO may have benefits for clinical anesthetic management, but it is important to recognize that use of HFNO has its own inherent risks. Several applications of HFNO are described below, each with its potential benefits and risks.
The authors are not advocating for or against the use of HFNO for these scenarios. Figure 1. Illustrates the three elements needed to initiate a fire: oxygen, fuel, ignition source. Reproduced from the APSF It is likely that an increasing number of anesthesia professionals will utilize HFNO in the operating room. One obstacle is that the HFNO equipment must be brought into the operating room and assembled every time it is used.
In the future, HFNO could be designed to directly connect to the anesthetic workstation for easier use. Due to regulatory and manufacturing limitations, however, it is unlikely that such modifications to incorporate HFNO apparatus will soon be available. Anesthesia professionals should encourage manufacturers to recognize these issues and work towards adding this feature to the next generation of machines. HFNO is a novel system of respiratory support, which allows delivery of oxygenation at variable concentrations, reduces the work of breathing, provides CPAP, and assists in CO 2 removal.
While it has a number of potential uses in anesthetic and perioperative practice, it also has definite relative and absolute contraindications. The potential risks of harm with HFNO use are probably underappreciated. Many questions regarding benefits and safety in specific clinical contexts remain.
Before using HFNO, education and insight into its use is highly recommended. Cooper is presently an anaesthesia consultant at the Green Lane Dept. Both Dr. Cooper and Griffiths have assisted with clinical research in HFNO for Fisher and Paykel Ltd, but have received no funds or other compensation from this entity. Support for LTOT is based on 2 landmark trials published nearly 4 decades ago.
These results form the basis for reimbursement and prescription of LTOT to this day. Oxygen therapy during activity and exercise has been shown to alleviate symptoms and maintain arterial oxygen saturation, but not improve long-term outcomes.
0コメント