DISCUSSION CONCLUSION REFERENCES CONCLUSION
REFERENCES PRE REQUIS LISTE DES FIGURES
LISTE DES TABLEAUX TABLE DES MATIERES ANNEXES
PRE REQUIS
En réanimation, l’échec de sevrage ventilatoire est courant, avec un risque non négligeable de détresse respiratoire chez les patients venant d’être extubés pouvant conduire à une réintubation (1). En effet, 10 à 15% de ces patients sont réintubés dans les 48h après leur extubation (1–3). Cette réintubation est associée à une durée de ventilation mécanique et une durée de séjour en réanimation prolongées entrainant une morbidité et une mortalité plus importante (2,4). La physiopathologie de cette détresse respiratoire aiguë est complexe.
Elle associe une obstruction des voies aériennes supérieures, une absence de toux efficace, des sécrétions respiratoires abondantes, des atélectasies, ainsi que des facteurs non respiratoires tels que l’encéphalopathie et l’insuffisance cardiaque (1,4–6). Dans la littérature, l’échec d’extubation est couramment défini comme le besoin de réintubation à 48h (1,7,8).
Actuellement, 3 différents types de méthodes non invasives sont disponibles pour prévenir ou traiter la détresse respiratoire en post-extubation : l’oxygénothérapie conventionnelle aux lunettes ou au masque haute concentration, couramment utilisée pour corriger l’hypoxémie après l’extubation, la ventilation non invasive (VNI) et plus récemment l’oxygénothérapie nasale à haut débit (OHD) via le système Optiflow.
La VNI est un traitement reconnu de la détresse respiratoire aiguë hypoxémique et hypercapnique (9). Son utilisation en post-extubation favorise le recrutement alvéolaire (10,11), permet de diminuer le travail respiratoire (1,12) et améliore l’oxygénation (11). Si parmi les patients présentant une détresse respiratoire aiguë en post-extubation, la VNI ne permet pas dans 10 à 50% des cas d’éviter la réintubation (13,14), 2 méta-analyses concluent cependant à l’intérêt de son utilisation précoce en post-extubation pour diminuer le taux de
réintubation (15,16). Malgré tout, la VNI reste un acte thérapeutique complexe et n’est pas toujours bien tolérée par les patients.
L’Optiflow est une méthode introduite plus récemment délivrant de l’oxygène à haut débit permettant une fraction inspirée en oxygène élevée. Cette technique améliore l’oxygénation, elle génère également une pression positive continue dans les voies respiratoires (17) permettant de réduire le travail respiratoire et permet un lavage de l’espace mort des voies aériennes supérieures (18). Les gaz inspirés sont humidifiés et réchauffés, améliorant ainsi le confort du patient et le drainage des sécrétions respiratoires, diminuant alors les obstructions des voies aériennes (17,18). Comparé à l’oxygénothérapie conventionnelle, en réanimation, l’Optiflow améliore l’oxygénation, le confort après l’extubation et prévient la détresse respiratoire post-extubation ainsi que le recours à une réintubation (19,20). De surcroit, Hernandez et al. a démontré que comparé à la VNI, l’Optiflow a le même effet sur la prévention de la réintubation et de la détresse respiratoire aiguë post extubation chez les populations les plus à risque de réintubation (3). Les données concernant la combinaison de l’Optiflow et de la VNI sont peu nombreuses. Il n’y a pas de données sur l’utilisation en association de la VNI et l’Optiflow pour traiter de manière curative la détresse respiratoire aigüe en post-extubation.
L’utilisation de ces techniques a soulevé des questions de sécurité pour le patient (13).
En effet, celles-ci peuvent retarder la réintubation dans certains cas, notamment en améliorant transitoirement le confort du patient et l’oxygénation, cela pouvant masquer temporairement une détresse respiratoire, et engendrer par la suite des conséquences défavorables en termes de morbi-mortalité.
Dans notre service de réanimation chirurgicale, l’introduction et l’utilisation de plus en plus fréquente de l’Optiflow a conduit à un changement de nos pratiques, celui-ci étant de plus
en plus utilisé en post-extubation. Ainsi l’objectif principal de notre étude est de comparer le taux de réintubation à 48h de l’extubation en réanimation entre 2 périodes, avant et après l’introduction de l’Optiflow en post-extubation. L’étude est présentée sous forme d’un article en Anglais.
Effect of changes in the use of noninvasive ventilation and high flow oxygen therapy on reintubation in a
surgical intensive care unit.
A Retrospective Cohort Study
Stanislas, ABRARD MD 1,2 * stanislas.abrard@chu-angers.fr Lorine, JEAN MD 1
lorinejean@hotmail.fr
Emmanuel RINEAU MD 1,2 Emmanuel.Rineau@chu-angers.fr Pauline, DUPRE MD 1
Pauline.dupre@chu-angers.fr Maxime LEGER, MD1, 3 Maxime.leger@chu-angers.Fr Sigismond, LASOCKI MD, PhD 1,2 SiLasocki@chu-angers.fr
1 Department of Anesthesiology and Intensive Care, University Hospital of Angers, 4 Rue Larrey, 49100 Angers, FRANCE
2 MITOVASC Institut, INSERM 1083 - CNRS 6015, University of Angers, 3 rue Roger Amsler, 49100 Angers, FRANCE
3 INSERM UMR 1246 - SPHERE, Nantes University, Tours University, Nantes, France.
ABSTRACT
Rationale: Reintubation after weaning from mechanical ventilation is relatively frequent and associated with poorer outcomes. Different methods, including noninvasive ventilation (NIV) and more recently high-flow oxygen (HFO), have been proposed after extubation to decrease the reintubation rate.
Objective: To compare the rate of reintubation between two periods, before and after the introduction of HFO in the postextubation period.
Method: Single-center cohort in a surgical ICU, during 2 phases (before, phase P1 from April 2015 to April 2016 and after the introduction of HFO, Phase P2 from April 2017 to April 2018). Adult patients hospitalized in ICU and mechanically ventilated for more than one day were included if they were extubated alive.
Main outcomes: The primary endpoint was the reintubation rate within 48 hours of extubation.
Results: 290 patients (median age 65 [50-74] years; 190 (65.5%) men) were included in the analysis (181 and 109 in P1 and P2 respectively). Postextubation use of noninvasive methods (NIV and/or HFO) was similar between the two phases (41 (22.7%) vs 29 (26.6%) patients, p=0.480), but was earlier in P2 (0h vs 4h, p=0.009) and HFO was significantly more used (24 (83%) vs 25 (61%), p=0.039). The need for reintubation within 48 hours after
extubation was significantly lower in P2 (4 (3.7%) vs 20 (11.0%), RR 0.30, 95%CI [0.08-0.92], p=0.034) but was similar at 7 days (10 (9.2%) vs 30 (16.6%), RR 0.47 [0.18-1.09], p=0.093).
Conclusion: The earlier implementation of noninvasive methods and the increased use of HFO between the 2 phases was accompanied by a lower extubation failure rate at 48 hours.
However, this effect was not persistent at 7 days.
INTRODUCTION
In intensive care units (ICUs), patients weaned from invasive mechanical ventilation are at risk of postextubation respiratory failure (ARF) and tracheal reintubation for mechanical ventilation1,2. Around 10 to 15% of patients are reintubated within 48 hours following extubation3, with an associated increase in morbidity, mortality and length of hospital stay4. The pathophysiology of respiratory failure after extubation includes upper airway obstruction, inadequate cough, atelectasis, encephalopathy, cardiac dysfunction2,5–7. Extubation failure is currently defined as the need for reintubation within 48h after extubation8,9. Three
“noninvasive methods” are available to avoid and/or treat post-extubation ARF: conventional oxygen therapy, high-flow conditioned oxygen therapy (HFO), and noninvasive ventilation (NIV). NIV is a recommended treatment for acute hypercapnic and hypoxemic ARF10. NIV administered in the postextubation period can recruit zones of alveolar collapse11,12, improve oxygenation13 and minimize the work of breathing1,14. Although the use of curative NIV is ineffective in 10 to 50% of patients with postextubation ARF to avoid tracheal reintubation, two meta-analyses concluded that early use of NIV could decrease reintubation rates15,16. HFO, a more recent method that delivers a high flow of high oxygen fraction, is able to generate a continuous positive airway pressure17, to reduce the work of breathing and to provide a washout of dead space in upper airways18. Compared with conventional oxygen therapy, high-flow conditioned oxygen therapy improves oxygenation and patients’ comfort after extubation and prevents postextubation ARF and reintubation in general populations of critically ill patients3,19. In comparison with NIV, HFO was not inferior to prevent reintubation and postextubation respiratory failure in high-risk adult patients who were extubated20. Currently, there is no known data on the comparison or combination of HFO and NIV to treat postextubation ARF (curative use). Moreover, the use of noninvasive methods has raised safety
concerns21. These therapies might increase the risk of worse outcomes by delaying reintubation because of the apparent improvements of patient comfort and oxygenation.
In our surgical ICU, the introduction of HFO has led to a change in practices, with a more frequent use of HFO in the postextubation period. The primary objective of this study was to compare the rate of reintubation 48 hours after extubation between two periods, before and after the introduction of HFO in this context.
METHODS
1. Study design and setting
The retrospective ARVENiO cohort study (Analyse Rétrospective de l’utilisation de la Ventilation Non-invasive et de l’Oxygénothérapie) was approved by the institutional review board of the French Anesthesiology and Critical Care Society (SFAR; 74 rue Raynouard; 75016 Paris France) (Chairperson Pr JE. Bazin) on 27 May 2019 (Ethical Committee N°IRB 00010254-2019‐094) and was registered at National Commission for Information Technology and Civil Liberties (DRCI-CGDE-FO-005), according to the French law22. The study is reported according to the STROBE statement.
This single-center, historical cohort was conducted in our 12-beds surgical ICU. We used data from 2 periods: from April 2015 to April 2016 (first phase, P1) and from April 2017 to April 2018 (second phase, P2). Between the two phases, physicians of the unit have gained experience and training on the benefits and use of HFO. No other changes in the respiratory management of patients was implemented.
2. Participants
All adult patients (age≥18 years) hospitalized in the intensive care unit, intubated, mechanically ventilated for a duration of more than one day and extubated alive during the two studied phases were included in our cohort.
3. Variables
Patient characteristics including age, body mass index, medical history (chronic obstructive pulmonary disease, arterial hypertension, sleep apnea syndrome, coronary artery disease), type of admission (medical, elective or emergency surgery), PaO2 / FiO2 ratio and reason for mechanical ventilation on admission if applicable, shock on admission (defined as the use of norepinephrine) and SAPS II score23 were recorded. The day of the first extubation was recorded, as well as the PaO2 (in mmHg) / FiO2 ratio immediately before extubation. The use of noninvasive methods, the time of implementation, the indication mentioned by the physician (preventive or curative), the duration of use and the settings (NIV: inspiratory pressure support, positive end expiratory pressure (PEEP), fraction of inspired oxygen (FiO2); HFO: flow and FiO2) were recorded during the first 7 days following extubation.
The primary endpoint was the reintubation rate within the first 48 hours after extubation (excluding reintubation for surgery). Secondary endpoints included the reintubation rate at 7th post-extubation day, reintubation delay, length of ICU stay, 28-day mortality and days without mechanical ventilation on day 28 (a value of 0 was assigned if the patient died).
4. Statistical analysis
Quantitative data are expressed as medians IQR and compared using the Mann–Whitney U test. Qualitative data are described using numbers (%) and compared using Fisher's exact test or Chi-2 if more than 1 degree of freedom.
For the primary endpoint, patients were separated into two groups, according to the phase (P1 or P2). A multivariable analysis of the occurrence of reintubation within the 48 hours after extubation (excluding reintubation for surgery) was compared by the Fisher’s exact test. The use of noninvasive methods described by frequency, indication and combination of methods were compared by the Fisher’s exact test. The survival analysis of the reintubation delays used a univariate log-rank test. A Kaplan Meier-type graphical representation was used to show the survival curves for each group. For the others endpoints, reintubation delay, length of ICU stay, 28-day mortality and days without mechanical ventilation during the first 28 days were compared using the Mann–Whitney U test.
For some outcomes (i.e., reintubation rate at 48 hours, reintubation rate at 7 days, and survival analysis of the probability of reintubation censored at seven days), multivariable analyses were performed. Reintubation rates were analyzed using a logistic regression, while the survival analysis of the probability of reintubation used a multivariable Cox cause specific model.
Association between primary endpoint and risk factor was expressed by Hazard Ratio cause specific (HR) taking into account the competitive risks of censoring reintubation by death or leaving the service prior to the need for reintubation. For all models, we applied a selection process to choose among candidate predictor variables that had univariable p-value < 0.15.
Analyses were performed using R version 3.6.3 and SPSS version 24.
RESULTS
1. Study participants
Figure 1 – Flow-chart.
NIV: Noninvasive ventilation. HFO: High-flow oxygenation. P1: Phase 1. P2: Phase 2.
The patient flow chart is presented in Figure 1. Among the 302 patients included in the two cohorts, 290 were included in the analysis (181 in P1 and 109 in P2). There was a majority of men, with a median age of 65 [50-74] years (Table 1). The Simplified Acute Physiologic Score was 48 [37-59] (Table 1). One hundred ninety-six patients (67.6%) were admitted after recent surgery. The clinical characteristics of the patients were similar in the two phases except for a
higher proportion of patients with coronary artery disease in P1 and a higher incidence of ARDS Type of ICU admission
Emergent surgery
Reason for ICU admission Pneumonia
P/F at extubation 287 217-359 288 216-366 283 220-348 0.778
Use of a noninvasive method 70 (24.1) 41 (22.7) 29 (26.6) 0.480
Time between extubation and noninvasive method implementation,
Table 1 – Patients baseline characteristics
n (% of phase). BMI: Body mass index. COPD: Chronic obstructive pulmonary disease. OSA:
Obstructive sleep apnea. ICU: Intensive care unit. ARDS: Acute respiratory distress syndrome. P/F:
Arterial partial pressure of oxygen (PaO2 in mmHg) / Fraction inspired of oxygen (FiO2). NIV:
Noninvasive ventilation. HFO: High-flow oxygenation.
The rate of patients receiving a noninvasive ventilation method was similar between the two
method was preventive in 4.5% of patients in P1 and 5.2% in P2 (p = 0.099). However, the noninvasive method was implemented significantly earlier in the P2 (0 [0-7] vs 4 [0-23] hours, p = 0.009). HFO was significantly more used in P2 (83% of patients with noninvasive method) vs 61% in P1 (p = 0.039) (Table 1). NIV was preferentially prescribed for few hour sessions, several times a day, whereas HFO was used almost continuously with an increase in daily HFO time performed between the two phases (13.5 [7.0-18.7] vs 20.9 17.7-22.5 hours per day per treated patient, p = 0.001) (Supplement Table 1).
2. Primary outcome
In total, 24 (8.3%) patients were reintubated within the first 48 hours after extubation.
Reintubation rate was significantly lower at 48 hours in the second phase of our cohort (20 (11.0%) vs 4 (3.7%) reintubations in P1 and P2 respectively, p = 0.028) (Table 2).
Outcomes All (n = 290) P1 (n = 181) P2 (n = 109) p
Reintubation within 48 hoursa, % 24 (8.3) 20 (11.0) 4 (3.7) 0.028
cause at 48 hours a Acute respiratory failure
Shock / cardiac arrest Neurologic failure Shock / cardiac arrest Neurologic failure
Days without ventilation on day 28 c 24.0 17.0-26.0 24.0 17.0-26.0 24.0 18.0-26.0 0.231 ICU length of stay, days 8.0 4.0-17.0 8.0 4.0-18.0 8.0 4.0-17.0 0.766
28-days mortality, % 16 (5.5) 11 (6.1) 5 (4.6) 0.792
Table 2 – Patients outcomes.
n (% of phase).
a Reintubation within 48 hours after extubation (excluding reintubation for surgery)
b Reintubation within 7 days after extubation (excluding reintubation for surgery)
c Value of 0 was affected if patient died during the 28 days after extubation.
ICU: Intensive care unit.
Multivariable analysis
We conducted a multivariate analysis to explore the factors associated with extubation success at 48 hours (Table 3). Phase 2 was independently associated with less reintubations at 48 hours (OR [95%CI] = 0.30 [0.08-0.92], p = 0.034), whereas the combined use of NIV and HFO was associated with an increased risk of reintubation (OR of 15.18 [2.78-83.16]).
Characteristics Reintubation at 48h
a (n=24) Reason for ICU admission
Pneumonia
Use of a noninvasive method None
Table 3 – Multivariate analysis of factors associated with a reintubation within 48 hours, integrating study phase.
n (% of group). Odds ratio [95 % Confidence Interval]: OR [95%IC]
a Reintubation during 48 postextubation hours (excluding reintubation for surgery)
BMI: Body mass index. COPD: Chronic obstructive pulmonary disease. OSA: Obstructive sleep apnea.
ICU: Intensive care unit. ARDS: Acute respiratory distress syndrome. P/F: Arterial partial pressure of oxygen (PaO2) / Fraction inspired of oxygen (FiO2).
3. Secondary outcomes
Forty (13.8%) patients were reintubated within the first 7 days after extubation. The main cause of reintubation was occurrence of ARF in the 2 phases (70% vs 70%). The median reintubation delay was not significantly earlier in P1 (1[0-3] vs 3[1-5] days, for P1 and P2, p
= 0.089). The reintubation rate at 7 days was not significantly different between the two phases (30 (16.6%) vs 10 (9.2%) in respectively P1 and P2, p = 0.082) (Table 2). We conducted a multivariate analysis to explore the factors associated with extubation success at 7th day. It showed that the study period was not independently associated with extubation failure during the first 7 days (OR 0.47 [0.18-1.09], p = 0.093) (Supplement Table 2). Survival analysis of the probability of reintubation censored at 7 days, calculated by adjusted multivariable Cox model (Supplement Table 3), was not different between the two periods (adjusted HR of extubation failure in phase 2 was 0.47 [0.22-1.04], p = 0.061) (Figure 2).
Figure 2 – Kaplan-Meier curves showing extubation success within 7 days according to study phase. P-value obtained with the log-rank test.
The use of noninvasive methods was independently associated with reintubation during the first 48 hours but not during the 7 days following the extubation (p = 0.013 and p = 0.104 respectively) (Table 3 and Supplement Table 2). The reintubation was not significantly associated with the use of HFO or NIV alone at 48 hours as at 7 days after extubation. However, after multivariable analysis and adjustment, combined use of NIV and HFO in the same patient was independently associated with extubation failure during the first 48 hours (OR 15.18
[2.78-83.16], p = 0.001) (Table 3). This association between combined use of NIV and HFO and extubation failure was also found during the first 7 days (OR 6.70 1.46-31.43, p = 0.013) (Supplement Table 2).
Finally, none of the other main clinical outcomes (day-28 mortality, ICU length of stay and ventilation-free days) were different the 2 phases (Table 2).
DISCUSSION
In this single-center retrospective cohort study, we confirmed an earlier and more extended postextubation use of HFO in the second period (P2). This was accompanied by a decrease by 70% of the reintubation rate at 48 hours but not at 7 days after extubation. We also observed that the combined use of NIV and HFO in the postextubation period was independently associated with extubation failure at 48 hours and 7 days.
We choose to assess reintubation rate at 48 hours because extubation failure is currently defined as the need to reintubate within 48 hours after extubation8,9. In our study, the overall postextubation ARF rate within 48 hours was about 8%, which is similar to the overall rate reported at 48-72 hours in previous randomized trials assessing noninvasive methods3,19. The rate of reintubation due to a non-respiratory cause is greater than 30% in our study. This finding is probably related to the high proportion of neurocritical patients in our ICU population (33.1 % of comatose patients at the admission). In these patients, reintubation for neurological failure is obviously more frequent7. Furthermore, in the context of neurological failure, the use of a noninvasive method is unlikely to avoid reintubation (22.5 % of reintubation for neurologic failure). This may have reduced the benefit of noninvasive methods in this study.
In our cohort, HFO therapy lasted longer than NIV (daily therapy duration and number of days). This may be related to a poorer tolerance of NIV, while comfort is improved under HFO3. Few data comparing NIV and HFO are available. They are inconclusive about oxygenation, work of breathing and need of intubation24. Hernandez et al.20 showed that in high-risk extubated patients, HFO was not inferior to NIV to prevent reintubation and postextubation respiratory failure. In line with previous published study, the reintubation was not associated specifically with one or the other methods in our study.
Combination of NIV and HFO has been proposed in order to prevent postextubation ARF. Thille et al.25 showed that combination of NIV and HFO after extubation significantly decreased the risk of reintubation compared with HFO alone. We observed that the reintubation rate was independently increased in the subgroup of patients treated with a combination of NIV and HFO (OR 15.18 [2.78-83.16], p = 0.001) (Table 3). The proportion of surgical patients was higher in our cohort. Difference in pathophysiology of ARF between surgical and medical patients could explained in part this discrepancy. In our cohort, the combined use of NIV and HFO was low (4.1%) without evolution over the phases. We can assume that combination of therapy was proposed to the more severe patients, explaining the increase in extubation failure in this sub-group.
Use of noninvasive methods has traditionally raised safety concerns21, notably on a potential increased risk of worse outcomes by delaying reintubation. Our results do not seem to support these concerns. The median reintubation delay tended to be earlier in P1 (1 [0-3] vs 3 [1-5]
days in P1 and P2, p = 0.089), without difference of 28-day mortality (p = 0.792), ICU length of stay (p = 0.766) and days without ventilation (p = 0.231).
Recently, Thille et al. proposed to extend to 7 days after extubation the delay to define extubation failure when using noninvasive methods26. Based on our results, it seems that an evaluation of extubation failure at 7 days is more clinically appropriate than at 48 hours.
Indeed, the reintubation rate we observed at 7 days (13.8% overall) was similar to those reported in previous studies25. We observed a non-significant lower rate of reintubation at 7 days in the second period, with an absolute difference of 7.4 %, which would be considered clinically significant and in the range of previous large multicenter RCTs assessing reintubation as the main outcome19,25. It is possible that our study did not have the power to detect statistical significance regarding this outcome.
Indeed, the reintubation rate we observed at 7 days (13.8% overall) was similar to those reported in previous studies25. We observed a non-significant lower rate of reintubation at 7 days in the second period, with an absolute difference of 7.4 %, which would be considered clinically significant and in the range of previous large multicenter RCTs assessing reintubation as the main outcome19,25. It is possible that our study did not have the power to detect statistical significance regarding this outcome.