Original Clinical Science
Humidified High Flow Nasal Cannula Supportive Therapy Improves Outcomes in Lung Transplant Recipients Readmitted to the Intensive Care Unit Because of Acute Respiratory Failure
Oriol Roca,1,2 Marina García de Acilu,1,3 Berta Caralt,1 Judit Sacanell,1 Joan R. Masclans,1,2 and ICU collaborators
Background. The effectiveness of humidified high flow nasal cannula (HFNC) in lung transplant (LTx) recipients readmitted to intensive care unit (ICU) because of acute respiratory failure (ARF) has not been determined to date. Methods. Retrospective
analysis of a prospectively assessed cohort of LTx patients who were readmitted to ICU because of ARF over a 5-year period. Patients received conventional oxygen therapy (COT) or HFNC (Optiflow, Fisher & Paykel, New Zealand) supportive therapy according to the attending physician’s criteria. Treatment failure was defined as the need for subsequent mechanical ventilation (MV). Results. Thirty-seven LTx recipients required ICU readmission, with a total of 40 episodes (18 COT vs. 22 HFNC). At ICU admission, no differences in comorbidities, pulmonary function, or median sequential organ failure assessment (COT, 4 [interquartile range, 4–6] vs. HFNC, 4 [interquartile range, 4–7]; P = 0.51) were observed. Relative risk of MV in patients with COT was 1.50 (95% confidence interval [95% CI], 1.02–2.21). The absolute risk reduction for MV with HFNC was 29.8%, and the number of patients needed to treat to prevent one intubation with HFNC was 3. Multivariate analysis showed that HFNC therapy was the only variable at ICU admission associated with a decreased risk of MV (odds ratio, 0.11 [95% CI, 0.02–0.69]; P = 0.02). Moreover, nonventilated patients had an increased survival rate (20.7% vs. 100%; relative rate 4.83 [95% CI, 2.37–9.86]; P < 0.001). No adverse events were associated with HFNC use. Conclusion. HFNC O2 therapy is feasible and safe and may decrease the need for MV in LTx recipients readmitted to the ICU because of ARF. (Transplantation 2015;99: 1092–1098)
D
uring the last two decades, there has been a substantial increase in the number of lung transplants (LTx) recorded in the International Society for Heart and Lung Transplant Registry.1 Indeed, lung transplant is now considered one of the main therapeutic options for end-stage lung diseases. However, because lung transplant patients may develop multiple complications, their 5-year survival remains poor in comparison with that of other solid organ transplant recipients.2 Infections and the clinical syndrome (bronchiolitis obliterans syndrome [BOS]) of chronic lung allograft rejection are the most important long-term complications.3 The appearance of these complications may lead to multiple hospital and intensive care unit (ICU) readmissions. In Received 11 March 2014. Accepted 26 August 2014. 1
Critical Care Department, Vall d’Hebron University Hospital, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain. 2
CibeRes, Instituto de Salud Carlos III, Madrid, Spain.
3
Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
The Critical Care Department has received research funding from Fisher & Paykel not related with the present study. The authors declare no conflicts of interest. O.R. and J.R.M. designed the study, analyzed and interpreted the data, and drafted the article. M.G. collected the data, analyzed and interpreted the data and drafted the article. B.C. and J.C. collected and interpreted the data. O.R., M.G., B.C., J. C., and J.R.M. critically revised the article for significant intellectual content and approved its final version.
1092
www.transplantjournal.com
general, lung transplant patients with complications present high levels of morbidity and mortality, and they may worsen their prognosis.4–7 Clearly, new treatment strategies are needed to improve prognosis. Although data on outcomes and prognostic factors of lung transplant patients readmitted to ICU are limited, systemic severity-of-illness and the need and duration of mechanical ventilation (MV) have been consistently associated with mortality.4–7 Therefore, strategies able to decrease the need for MV would be especially useful. Heated humidified high flow nasal cannula (HFNC) oxygen therapy has recently been described as a safe and useful supportive therapy in the general management of acute respiratory failure (ARF).8–13 Preliminary results in ARF patients show that HFNC may improve comfort and oxygenation.8,11–15 However, no data have been reported regarding ICU collaborators: Serra, Joaquim, Ruiz, Juan Carlos, Ruiz, Adolf, Caballero, Jesús, Pérez, Marcos, Pérez, Agueda, Alcaraz, Rosa, Laborda, César, Gracia, Rosa Maria, Sánchez, Ana, Porta, Isabel, Alonso, José, Farré, Mercè, Pérez, Purificación, Leal, Sandra. Correspondence: Oriol Roca, M.D., Ph.D., Critical Care Department, Vall d’Hebron University Hospital, P. Vall d’Hebron 119-129, Annexe 5a plantaAG, E08035, Barcelona, Spain. ([email protected]). Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0041-1337/15/9905-1092 DOI: 10.1097/TP.0000000000000460
Transplantation
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
■
May 2015
■
Volume 99
■
Number 5
Roca et al
© 2014 Wolters Kluwer
its effect on the need for invasive MVor its effect on ICU mortality. We hypothesized that HFNC use in the general management of ARF patients may decrease both the need for MV and ICU mortality. To test this hypothesis, we compared the clinical course of lung transplant patients requiring ICU readmission because of ARF treated with two different oxygenation supportive therapies (conventional oxygen therapy vs. HFNC). RESULTS During the 5-year study period, 37 LTx recipients required readmission to the ICU, with a total of 40 episodes. Thirty-five (94.6%) patients were admitted once, one (2.7%) twice and another (2.7%) three times. The 40 episodes were divided in two different cohorts according to the oxygenation therapy provided (conventional oxygen therapy [COT]: 18 readmissions vs. HFNC: 22). Yearly distribution of ICU readmissions is presented in Figure 1. None of the patients was transferred from outlying center. The treatment with HFNC was started immediately on ICU admission. The baseline characteristics of the study population are reported in Table 1. In the COT group, other causes of ARF include bronchial stenosis, extrapulmonary acute respiratory distress syndrome (ARDS), cardiogenic pulmonary edema and end-stage BOS. Cardiogenic pulmonary edema was the other cause of ARF in the HFNC group. No differences in the number of patients with severe BOS were observed (COT, 7 [39%] vs. HFNC 12 [54%]; P = 0.52). The general distribution of the patients readmitted according to the respiratory therapy used is shown in Table 2. Failure to achieve correct oxygenation was the primary cause of intubation in all patients who needed to be mechanically ventilated. Relative risk of MV in patients with COT was 1.50 (95% confidence interval [95% CI], 1.02–2.21), the absolute risk reduction for MV with HFNC was 29.8%, and the needed to treat to prevent one intubation with HFNC was 3. The patient with end-stage BOS, who was treated with COT, had a do-not-intubate order and could be discharged to the ward where he finally died. Another patient treated with COT and one treated with HFNC were discharged from ICU but died in the respiratory ward. To determine which variables were independently associated with need for MV, a backward stepwise logistic regression analysis was performed. Presence of ARDS or acute renal failure, need for vasopressors during their ICU stay, and HFNC therapy were included in the multivariate
FIGURE 1. Yearly distribution of ICU readmissions.
1093
TABLE 1.
General characteristics of the population included according to the supportive treatment received COT
HFNC
(n = 18)
(n = 22)
P
56.0 (35.7-60.2) 13 (59.1%)
0.48 0.89 0.15
Age, yr 53.5 (27.0-58.2) Sex (male) 11 (61.1%) Pretransplant diagnosis COPD 7 (38.9%) Cystic fibrosis 5 (27.8%) ILD 5 (27.8%) Others 1 (5.6%) Transplant operation Bilateral 11 (61.1%) Right 3 (16.7%) Left 4 (22.2%) Pre-ICU admission complications LRTI 11 (61.1%) AR 6 (33.3%) CLAD 3 (16.7%) PGD 2 (11.1%) Last PFT previous ICU readmission FEV1, L 1.30 (0.68-1.77) FEV1, % 47.0 (27.0-58.5) FVC, L 1.78 (1.25-2.70) FVC, % 46.5 (42.7-59.2) Time after transplant 244 (66-759) at ICU readmission
4 (18.2%) 3 (13.6%) 10 (45.5%) 5 (22.7%) 0.75 11 (50%) 4 (18.2%) 7 (31.8%) 10 (45.5%) 6 (27.3%) 8 (36.4%) 6 (27.3%)
0.49 0.91 0.29 0.23
1.68 (0.94-2.06) 50.0 (34.5-60.5) 1.89 (1.38-2.57) 44.0 (40.0-68.7) 305 (106-1200)
0.22 0.51 0.77 0.72 0.58
COT, conventional oxygen therapy; HFNC, high flow nasal cannula; COPD, chronic obstructive pulmonary disease; ILD, interstitial lung disease; LRTI, lower respiratory tract infection; AR, acute rejection; CLAD, Chronic lung allograft dysfunction; PGD, primary graft dysfunction; PFT, pulmonary function test; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity.
analysis (Table 3). The model showed an association between HFNC and decreased risk of MV (odds ratio [OR], 0.43 [95% CI, 0.002–0.88]; P = 0.04). In contrast, as expected, developing of ARDS during ICU stay was independently associated with increased risk of MV (OR, 28.23; 95% CI, 1.82–437.78). As it could be also important to determine which variables were associated with further need for MV at the moment of ICU readmission, another model was built including the presence of ARDS, renal failure, and shock at ICU readmission (Table 3). In this case, HFNC therapy was the only variable associated with decreased risk of MV (OR, 0.11; 95% CI, 0.02–0.69; P = 0.02). Therefore, a patient without organ failure at ICU admission (no ARDS, no renal failure, and no shock) who was treated with HFNC had a predicted probability of MV of 34.6%; however, if the same patient was treated with COT, the probability of MV would increase to 83.5%. Likewise, ARDS patients with no other organ failures treated with HFNC had a predicted probability of MV of 84.7%, whereas if the patient was treated with COT the probability of MV increased to 98.1%. During their ICU stay, as expected, ICU nonsurvivors had a higher prevalence of ARDS, renal failure, and shock and more frequently needed intubation and MV (Table S1, SDC, http://links.lww.com/TP/B72). In fact, as could be also expected, nonventilated patients had an increased survival rate (100% vs. 20.7%; relative rate [RR] 4.83; 95% CI, 2.37–9.86; P < 0.001).
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
1094
Transplantation
■
May 2015
■
Volume 99
■
Number 5
www.transplantjournal.com
TABLE 2.
Characteristics of the LTx patients readmitted to ICU COT
APACHE II score SOFA at ICU readmission Quadrants involved in chest x-ray Reason of ARF Infection Rejection Others Baseline respiratory variables (with COT) SpO2, % Respiratory rate, bpm Need of MV Heart rate at ICU readmission, bpm ARDS At ICU readmission During their course in ICU Shock At ICU readmission During their course in ICU Renal failure At ICU readmission During their course in ICU Renal replacement therapy Heart failure Bilirubin, mg/dL Outcomes ICU mortality Hospital mortality ICU LOS (for survivors), days ICU LOS (for all), days Hospital LOS (for survivors), days Hospital LOS (for all), days
HFNC
(n = 18)
(n = 22)
P
20 (19-25) 4 (4-6) 2 (1-3)
21 (18-25) 4 (4-7) 2 (1-3)
0.61 0.51 0.89 0.64
13 (72.2%) 1 (5.6%) 4 (22.2%)
20 (91.0%) 1 (4.5%) 1 (4.5%)
94 (91-98) 20 (16-28) 16 (88.9%) 115 (93-130)
92 (90-94) 28 (22-30) 13 (59.1%) 103 (92-114)
0.11 0.02 0.07 0.39
3 (16.7%) 12 (66.7%)
7 (31.8%) 16 (72.7%)
0.31 0.68
7 (38.9%) 12 (66.7%)
5 (22.7%) 13 (59.1%)
0.40 0.76
4 (22.2%) 12 (66.7%) 2 (11%) 1 (5.5%) 0.35 (0.15-0.6)
5 (22.7%) 11 (50.0%) 4 (18.1%) 1 (4.7%) 0.35 (0.1–0.52)
0.67 0.37 0.67 1.00 0.54
13 (72%) 15 (83%) 6 (3-39) 9 (4-45) 33 (11-84) 32 (12-60)
10 (45.5%) 11 (50.0%) 9 (6-15) 14 (7-29) 41 (22-51) 35 (21-49)
0.09 0.03 0.19 0.74 0.78 0.73
Results are expressed as median (interquartile range) or frequency (percentage). LTx, lung transplant; ICU, intensive care unit; COT, conventional oxygen therapy; HFNC, high flow nasal cannula; APACHE II, Acute Physiology and Chronic Health Evaluation; SOFA, sequential organ failure assessment; ARF, acute respiratory failure; ABG, arterial blood gases; MV, mechanical ventilation; ARDS, acute respiratory distress syndrome; LOS, length of stay.
Among patients treated with HFNC, the presence of ARDS (HFNC failure 44.4% vs. HFNC success 92.3%; P = 0.02) or need for vasopressors (HFNC failure 22.2% vs. HFNC success84.6%; P = 0.02) during ICU stay was a significant
determinant of treatment failure (Table 4). Seventeen(100%) patients who met ARDS criteria and who developed renal failure and shock during their ICU stay also required intubation. In contrast, three (100%) patients without infiltrates
TABLE 3.
Multivariate logistic regression analysis of need for mechanical ventilation β
SE
P
OR
95% CI
−3.15 3.34 2.33 0.23
1.54 1.39 1.22
0.041 0.017 0.056
0.04 28.23 10.25
0.002-0.88 1.82-437.78 0.95-111.12
−2.25 2.35 1.93 1.61
0.96 1.22 1.23
0.019 0.054 0.117
0.11 10.46 6.89
0.02-0.69 0.96-114.24 0.61-77.04
a
Model 1 (step 2 ) HFNC ARDS during ICU stay RF during ICU stay Constant Model 2 (step 2b) HFNC ARDS at ICU readmission RF at ICU readmission Constant a
Variables entered in step 1: HFNC, ARDS during ICU stay, RF during ICU stay and shock during ICU stay. Variables entered in step 1: HFNC, ARDS at ICU readmission, RF at ICU readmission and Shock at ICU readmission. HFNC, high flow nasal cannula; β, regression coefficient; SE, standard error; OR, odds ratio; 95% CI, 95% confidence interval; ARDS, acute respiratory distress syndrome; ICU, intensive care unit; RF, respiratory failure. b
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Roca et al
© 2014 Wolters Kluwer
1095
TABLE 4.
Characteristics of the LTx patients readmitted to ICU
APACHE II score SOFA at ICU admission Quadrants involved in chest x-ray Reason of ARF Infection Rejection Others Respiratory variables after 30 min of HFNC treatment Flow rate, lpm Respiratory rate, bpm PaO2/FIO2, mm Hg PaCO2, mm Hg ARDS At ICU readmission During their ICU stay Shock At ICU readmission During their ICU stay Renal failure At ICU readmission During their ICU stay Outcomes ICU mortality Hospital mortality ICU LOS (ICU survivors), days ICU LOS (all patients), days Hospital LOS (hospital survivors), days Hospital LOS (all patients), days
HFNC success (n = 9)
HFNC failure (n = 13)
P
20 (17-22) 4 (4-6) 1 (1-2.5)
21 (18-26) 5 (4-7) 3 (2-3)
0.25 0.32 0.05 0.47
9 (100%) 0 0
11 (84.6%) 1 (7.7%) 1 (7.7%)
25 (20-30) 28 (20-28) 93 (86-265) 38 (33-43)
30 (20-30) 28 (24-32) 115 (90-146) 41 (39-43)
0.53 0.48 0.71 0.15
1 (11.1%) 4 (44.4%)
4 (30.8%) 12 (92.3%)
0.47 0.02
2 (22.2%) 2 (22.2%)
3 (23.1%) 11 (84.6%)
1.0 0.02
1 (11.1%) 2 (22.2%)
4 (30.8%) 9 (69.2%)
0.47 0.08
0 1 (11.1%) 8 (5-10) 8 (5-10) 31 (20-56) 25 (21-44)
10 (76.9%) 10 (76.9%) 16 (16-41) 20 (15-37) 49 ( 44-53) 37 (17-52)
Humidified High Flow Nasal Cannula Supportive Therapy Improves Outcomes in Lung Transplant Recipients Readmitted to the Intensive Care Unit Because of Acute Respiratory Failure
Oriol Roca,1,2 Marina García de Acilu,1,3 Berta Caralt,1 Judit Sacanell,1 Joan R. Masclans,1,2 and ICU collaborators
Background. The effectiveness of humidified high flow nasal cannula (HFNC) in lung transplant (LTx) recipients readmitted to intensive care unit (ICU) because of acute respiratory failure (ARF) has not been determined to date. Methods. Retrospective
analysis of a prospectively assessed cohort of LTx patients who were readmitted to ICU because of ARF over a 5-year period. Patients received conventional oxygen therapy (COT) or HFNC (Optiflow, Fisher & Paykel, New Zealand) supportive therapy according to the attending physician’s criteria. Treatment failure was defined as the need for subsequent mechanical ventilation (MV). Results. Thirty-seven LTx recipients required ICU readmission, with a total of 40 episodes (18 COT vs. 22 HFNC). At ICU admission, no differences in comorbidities, pulmonary function, or median sequential organ failure assessment (COT, 4 [interquartile range, 4–6] vs. HFNC, 4 [interquartile range, 4–7]; P = 0.51) were observed. Relative risk of MV in patients with COT was 1.50 (95% confidence interval [95% CI], 1.02–2.21). The absolute risk reduction for MV with HFNC was 29.8%, and the number of patients needed to treat to prevent one intubation with HFNC was 3. Multivariate analysis showed that HFNC therapy was the only variable at ICU admission associated with a decreased risk of MV (odds ratio, 0.11 [95% CI, 0.02–0.69]; P = 0.02). Moreover, nonventilated patients had an increased survival rate (20.7% vs. 100%; relative rate 4.83 [95% CI, 2.37–9.86]; P < 0.001). No adverse events were associated with HFNC use. Conclusion. HFNC O2 therapy is feasible and safe and may decrease the need for MV in LTx recipients readmitted to the ICU because of ARF. (Transplantation 2015;99: 1092–1098)
D
uring the last two decades, there has been a substantial increase in the number of lung transplants (LTx) recorded in the International Society for Heart and Lung Transplant Registry.1 Indeed, lung transplant is now considered one of the main therapeutic options for end-stage lung diseases. However, because lung transplant patients may develop multiple complications, their 5-year survival remains poor in comparison with that of other solid organ transplant recipients.2 Infections and the clinical syndrome (bronchiolitis obliterans syndrome [BOS]) of chronic lung allograft rejection are the most important long-term complications.3 The appearance of these complications may lead to multiple hospital and intensive care unit (ICU) readmissions. In Received 11 March 2014. Accepted 26 August 2014. 1
Critical Care Department, Vall d’Hebron University Hospital, Vall d’Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain. 2
CibeRes, Instituto de Salud Carlos III, Madrid, Spain.
3
Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
The Critical Care Department has received research funding from Fisher & Paykel not related with the present study. The authors declare no conflicts of interest. O.R. and J.R.M. designed the study, analyzed and interpreted the data, and drafted the article. M.G. collected the data, analyzed and interpreted the data and drafted the article. B.C. and J.C. collected and interpreted the data. O.R., M.G., B.C., J. C., and J.R.M. critically revised the article for significant intellectual content and approved its final version.
1092
www.transplantjournal.com
general, lung transplant patients with complications present high levels of morbidity and mortality, and they may worsen their prognosis.4–7 Clearly, new treatment strategies are needed to improve prognosis. Although data on outcomes and prognostic factors of lung transplant patients readmitted to ICU are limited, systemic severity-of-illness and the need and duration of mechanical ventilation (MV) have been consistently associated with mortality.4–7 Therefore, strategies able to decrease the need for MV would be especially useful. Heated humidified high flow nasal cannula (HFNC) oxygen therapy has recently been described as a safe and useful supportive therapy in the general management of acute respiratory failure (ARF).8–13 Preliminary results in ARF patients show that HFNC may improve comfort and oxygenation.8,11–15 However, no data have been reported regarding ICU collaborators: Serra, Joaquim, Ruiz, Juan Carlos, Ruiz, Adolf, Caballero, Jesús, Pérez, Marcos, Pérez, Agueda, Alcaraz, Rosa, Laborda, César, Gracia, Rosa Maria, Sánchez, Ana, Porta, Isabel, Alonso, José, Farré, Mercè, Pérez, Purificación, Leal, Sandra. Correspondence: Oriol Roca, M.D., Ph.D., Critical Care Department, Vall d’Hebron University Hospital, P. Vall d’Hebron 119-129, Annexe 5a plantaAG, E08035, Barcelona, Spain. ([email protected]). Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0041-1337/15/9905-1092 DOI: 10.1097/TP.0000000000000460
Transplantation
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
■
May 2015
■
Volume 99
■
Number 5
Roca et al
© 2014 Wolters Kluwer
its effect on the need for invasive MVor its effect on ICU mortality. We hypothesized that HFNC use in the general management of ARF patients may decrease both the need for MV and ICU mortality. To test this hypothesis, we compared the clinical course of lung transplant patients requiring ICU readmission because of ARF treated with two different oxygenation supportive therapies (conventional oxygen therapy vs. HFNC). RESULTS During the 5-year study period, 37 LTx recipients required readmission to the ICU, with a total of 40 episodes. Thirty-five (94.6%) patients were admitted once, one (2.7%) twice and another (2.7%) three times. The 40 episodes were divided in two different cohorts according to the oxygenation therapy provided (conventional oxygen therapy [COT]: 18 readmissions vs. HFNC: 22). Yearly distribution of ICU readmissions is presented in Figure 1. None of the patients was transferred from outlying center. The treatment with HFNC was started immediately on ICU admission. The baseline characteristics of the study population are reported in Table 1. In the COT group, other causes of ARF include bronchial stenosis, extrapulmonary acute respiratory distress syndrome (ARDS), cardiogenic pulmonary edema and end-stage BOS. Cardiogenic pulmonary edema was the other cause of ARF in the HFNC group. No differences in the number of patients with severe BOS were observed (COT, 7 [39%] vs. HFNC 12 [54%]; P = 0.52). The general distribution of the patients readmitted according to the respiratory therapy used is shown in Table 2. Failure to achieve correct oxygenation was the primary cause of intubation in all patients who needed to be mechanically ventilated. Relative risk of MV in patients with COT was 1.50 (95% confidence interval [95% CI], 1.02–2.21), the absolute risk reduction for MV with HFNC was 29.8%, and the needed to treat to prevent one intubation with HFNC was 3. The patient with end-stage BOS, who was treated with COT, had a do-not-intubate order and could be discharged to the ward where he finally died. Another patient treated with COT and one treated with HFNC were discharged from ICU but died in the respiratory ward. To determine which variables were independently associated with need for MV, a backward stepwise logistic regression analysis was performed. Presence of ARDS or acute renal failure, need for vasopressors during their ICU stay, and HFNC therapy were included in the multivariate
FIGURE 1. Yearly distribution of ICU readmissions.
1093
TABLE 1.
General characteristics of the population included according to the supportive treatment received COT
HFNC
(n = 18)
(n = 22)
P
56.0 (35.7-60.2) 13 (59.1%)
0.48 0.89 0.15
Age, yr 53.5 (27.0-58.2) Sex (male) 11 (61.1%) Pretransplant diagnosis COPD 7 (38.9%) Cystic fibrosis 5 (27.8%) ILD 5 (27.8%) Others 1 (5.6%) Transplant operation Bilateral 11 (61.1%) Right 3 (16.7%) Left 4 (22.2%) Pre-ICU admission complications LRTI 11 (61.1%) AR 6 (33.3%) CLAD 3 (16.7%) PGD 2 (11.1%) Last PFT previous ICU readmission FEV1, L 1.30 (0.68-1.77) FEV1, % 47.0 (27.0-58.5) FVC, L 1.78 (1.25-2.70) FVC, % 46.5 (42.7-59.2) Time after transplant 244 (66-759) at ICU readmission
4 (18.2%) 3 (13.6%) 10 (45.5%) 5 (22.7%) 0.75 11 (50%) 4 (18.2%) 7 (31.8%) 10 (45.5%) 6 (27.3%) 8 (36.4%) 6 (27.3%)
0.49 0.91 0.29 0.23
1.68 (0.94-2.06) 50.0 (34.5-60.5) 1.89 (1.38-2.57) 44.0 (40.0-68.7) 305 (106-1200)
0.22 0.51 0.77 0.72 0.58
COT, conventional oxygen therapy; HFNC, high flow nasal cannula; COPD, chronic obstructive pulmonary disease; ILD, interstitial lung disease; LRTI, lower respiratory tract infection; AR, acute rejection; CLAD, Chronic lung allograft dysfunction; PGD, primary graft dysfunction; PFT, pulmonary function test; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity.
analysis (Table 3). The model showed an association between HFNC and decreased risk of MV (odds ratio [OR], 0.43 [95% CI, 0.002–0.88]; P = 0.04). In contrast, as expected, developing of ARDS during ICU stay was independently associated with increased risk of MV (OR, 28.23; 95% CI, 1.82–437.78). As it could be also important to determine which variables were associated with further need for MV at the moment of ICU readmission, another model was built including the presence of ARDS, renal failure, and shock at ICU readmission (Table 3). In this case, HFNC therapy was the only variable associated with decreased risk of MV (OR, 0.11; 95% CI, 0.02–0.69; P = 0.02). Therefore, a patient without organ failure at ICU admission (no ARDS, no renal failure, and no shock) who was treated with HFNC had a predicted probability of MV of 34.6%; however, if the same patient was treated with COT, the probability of MV would increase to 83.5%. Likewise, ARDS patients with no other organ failures treated with HFNC had a predicted probability of MV of 84.7%, whereas if the patient was treated with COT the probability of MV increased to 98.1%. During their ICU stay, as expected, ICU nonsurvivors had a higher prevalence of ARDS, renal failure, and shock and more frequently needed intubation and MV (Table S1, SDC, http://links.lww.com/TP/B72). In fact, as could be also expected, nonventilated patients had an increased survival rate (100% vs. 20.7%; relative rate [RR] 4.83; 95% CI, 2.37–9.86; P < 0.001).
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
1094
Transplantation
■
May 2015
■
Volume 99
■
Number 5
www.transplantjournal.com
TABLE 2.
Characteristics of the LTx patients readmitted to ICU COT
APACHE II score SOFA at ICU readmission Quadrants involved in chest x-ray Reason of ARF Infection Rejection Others Baseline respiratory variables (with COT) SpO2, % Respiratory rate, bpm Need of MV Heart rate at ICU readmission, bpm ARDS At ICU readmission During their course in ICU Shock At ICU readmission During their course in ICU Renal failure At ICU readmission During their course in ICU Renal replacement therapy Heart failure Bilirubin, mg/dL Outcomes ICU mortality Hospital mortality ICU LOS (for survivors), days ICU LOS (for all), days Hospital LOS (for survivors), days Hospital LOS (for all), days
HFNC
(n = 18)
(n = 22)
P
20 (19-25) 4 (4-6) 2 (1-3)
21 (18-25) 4 (4-7) 2 (1-3)
0.61 0.51 0.89 0.64
13 (72.2%) 1 (5.6%) 4 (22.2%)
20 (91.0%) 1 (4.5%) 1 (4.5%)
94 (91-98) 20 (16-28) 16 (88.9%) 115 (93-130)
92 (90-94) 28 (22-30) 13 (59.1%) 103 (92-114)
0.11 0.02 0.07 0.39
3 (16.7%) 12 (66.7%)
7 (31.8%) 16 (72.7%)
0.31 0.68
7 (38.9%) 12 (66.7%)
5 (22.7%) 13 (59.1%)
0.40 0.76
4 (22.2%) 12 (66.7%) 2 (11%) 1 (5.5%) 0.35 (0.15-0.6)
5 (22.7%) 11 (50.0%) 4 (18.1%) 1 (4.7%) 0.35 (0.1–0.52)
0.67 0.37 0.67 1.00 0.54
13 (72%) 15 (83%) 6 (3-39) 9 (4-45) 33 (11-84) 32 (12-60)
10 (45.5%) 11 (50.0%) 9 (6-15) 14 (7-29) 41 (22-51) 35 (21-49)
0.09 0.03 0.19 0.74 0.78 0.73
Results are expressed as median (interquartile range) or frequency (percentage). LTx, lung transplant; ICU, intensive care unit; COT, conventional oxygen therapy; HFNC, high flow nasal cannula; APACHE II, Acute Physiology and Chronic Health Evaluation; SOFA, sequential organ failure assessment; ARF, acute respiratory failure; ABG, arterial blood gases; MV, mechanical ventilation; ARDS, acute respiratory distress syndrome; LOS, length of stay.
Among patients treated with HFNC, the presence of ARDS (HFNC failure 44.4% vs. HFNC success 92.3%; P = 0.02) or need for vasopressors (HFNC failure 22.2% vs. HFNC success84.6%; P = 0.02) during ICU stay was a significant
determinant of treatment failure (Table 4). Seventeen(100%) patients who met ARDS criteria and who developed renal failure and shock during their ICU stay also required intubation. In contrast, three (100%) patients without infiltrates
TABLE 3.
Multivariate logistic regression analysis of need for mechanical ventilation β
SE
P
OR
95% CI
−3.15 3.34 2.33 0.23
1.54 1.39 1.22
0.041 0.017 0.056
0.04 28.23 10.25
0.002-0.88 1.82-437.78 0.95-111.12
−2.25 2.35 1.93 1.61
0.96 1.22 1.23
0.019 0.054 0.117
0.11 10.46 6.89
0.02-0.69 0.96-114.24 0.61-77.04
a
Model 1 (step 2 ) HFNC ARDS during ICU stay RF during ICU stay Constant Model 2 (step 2b) HFNC ARDS at ICU readmission RF at ICU readmission Constant a
Variables entered in step 1: HFNC, ARDS during ICU stay, RF during ICU stay and shock during ICU stay. Variables entered in step 1: HFNC, ARDS at ICU readmission, RF at ICU readmission and Shock at ICU readmission. HFNC, high flow nasal cannula; β, regression coefficient; SE, standard error; OR, odds ratio; 95% CI, 95% confidence interval; ARDS, acute respiratory distress syndrome; ICU, intensive care unit; RF, respiratory failure. b
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Roca et al
© 2014 Wolters Kluwer
1095
TABLE 4.
Characteristics of the LTx patients readmitted to ICU
APACHE II score SOFA at ICU admission Quadrants involved in chest x-ray Reason of ARF Infection Rejection Others Respiratory variables after 30 min of HFNC treatment Flow rate, lpm Respiratory rate, bpm PaO2/FIO2, mm Hg PaCO2, mm Hg ARDS At ICU readmission During their ICU stay Shock At ICU readmission During their ICU stay Renal failure At ICU readmission During their ICU stay Outcomes ICU mortality Hospital mortality ICU LOS (ICU survivors), days ICU LOS (all patients), days Hospital LOS (hospital survivors), days Hospital LOS (all patients), days
HFNC success (n = 9)
HFNC failure (n = 13)
P
20 (17-22) 4 (4-6) 1 (1-2.5)
21 (18-26) 5 (4-7) 3 (2-3)
0.25 0.32 0.05 0.47
9 (100%) 0 0
11 (84.6%) 1 (7.7%) 1 (7.7%)
25 (20-30) 28 (20-28) 93 (86-265) 38 (33-43)
30 (20-30) 28 (24-32) 115 (90-146) 41 (39-43)
0.53 0.48 0.71 0.15
1 (11.1%) 4 (44.4%)
4 (30.8%) 12 (92.3%)
0.47 0.02
2 (22.2%) 2 (22.2%)
3 (23.1%) 11 (84.6%)
1.0 0.02
1 (11.1%) 2 (22.2%)
4 (30.8%) 9 (69.2%)
0.47 0.08
0 1 (11.1%) 8 (5-10) 8 (5-10) 31 (20-56) 25 (21-44)
10 (76.9%) 10 (76.9%) 16 (16-41) 20 (15-37) 49 ( 44-53) 37 (17-52)
