A total of 1453 patients with confirmed influenza infection in ED over a 2-year period were initially recruited. After reviewing electronic medical records, 180 patients met inclusion criteria and 18 patients were excluded by exclusion criteria (14 patients and family members who signed do-not-attempt-resuscitation orders and 4 patients who were transferred to other hospitals), resulting in final inclusion of 162 patients.
Among these 162 patients, there were 72 patients (44%) who failed NIV use, 64 patients (88.9%) were intubated in 24 hours, average time to intubation was 12 hours (95%CI 11-18) and 12 patients died after being intubated post NIV failure. NIV setting: all patients used BiPAP ST mode and no significant differences in tidal volume and initial PEEP. Significant differences in patient characteristics, including SOFA score, PF ratio and new quadrant infiltration in chest radiography were observed between NIV failure group and NIV success group. The patient’s demographic data are show in Table 1.
Table 1 Demographics and baseline characteristics
Variable
|
NIV failure group
(N = 72)
|
NIV success group
(N = 90)
|
P value
|
Age (year), median (IQR)
|
79 (74-82)
|
77 (75-81)
|
0.920
|
Male sex, N (%)
|
34 (47.2)
|
32 (35.6)
|
0.327
|
Comorbidities, N (%)
Hypertension
Diabetic mellitus
Chronic Obstructive Pulmonary Disease
Asthma
Coronary artery disease
Heart failure
End stage renal disease
Neuromuscular disease
Immunosuppression
Malignancy
|
60 (83.3)
36 (50.0)
12 (16.7)
16 (8.3)
34 (47.2)
30 (41.7)
14 (19.4)
2 (2.8)
12 (16.7)
8 (11.1)
|
66 (73.3)
36 (40.0)
24 (26.7)
8 (8.9)
34 (37.8)
26 (28.9)
10 (11.1)
12 (13.3)
4 (4.4)
14 (15.6)
|
0.367
0.417
0.262
0.905
0.44
0.26
0.319
0.122
0.10
0.537
|
Influenza, N (%)
Influenza A
Influenza B
|
50(69.4)
22 (30.6)
|
54 (60.0)
36 (40.0)
|
|
Systolic blood pressure, median (IQR) mmHg
|
147 (137-156)
|
142 (135-148)
|
0.552
|
Respiratory rate, median (IQR) bpm
|
26 (24-28)
|
24 (24-26)
|
0.556
|
**SpO2 (%), median (IQR)
|
93 (92-94)
|
92 (92-94)
|
0.373
|
***APACHE Score, median (IQR)
|
15 (13-16)
|
14 (12-15)
|
0.499
|
****SOFA Score, median (IQR)
|
6 (6-7)
|
1 (1-2)
|
0.001
|
*****PF ratio (mmHg), median (IQR)
|
168.7 (150-189)
|
270.5 (260-300)
|
0.001
|
*******PF ratio level, median (IQR)
|
2(2-3)
|
1(0-1)
|
0.001
|
Arterial blood gas
pH, median (IQR)
PaCO2, median (IQR) mmHg
HCO3, median (IQR) mEq/L
Lactate level, median (IQR) mmol/L
|
7.44 (7.40-7.45)
36.1 (33-39)
24.2 (22.9-254.)
1.55 (1.5-1.8)
|
7.43 (7.41-7.45)
35 (34-38)
24 (23-25.2)
1.65 (1.4-2.0)
|
0.654
0.271
0.449
0.918
|
Number infiltrated quadrant on chest radiography, median (IQR)
|
2 (1-2)
|
1 (1-2)
|
0.001
|
Non-invasive setting
Tidal volume (ml)
Tidal volume (ml/kg)
********Initial PEEP (cmH2O)
|
436 (430-450)
7.4 (6.4-8.2)
8 (6-8)
|
430 (430-440)
7.2 (6.2-7.9)
8 (6-8)
|
0.408
0.542
0.526
|
**SpO2; Oxygen saturation, ***APACHE Score; Acute Physiology and Chronic Health Evaluation Score, ****SOFA Score; Sequential Organ Failure Assessment Score, *****PF ratio; Ratio of arterial oxygen partial pressure to fractional inspired oxygen
******PF ratio level; 0 = PF ratio > 200 mmHg with non-PEEP, 1 = PF ratio < 200 mmHg with non-PEEP or < 300 mmHg with PEEP > 5 cmH2O, 2 = PF ratio < 100 mmHg with non-PEEP or < 200 mmHg with PEEP > 5 cmH2O, 3 = PF ratio <100 mmHg with PEEP > 5 cmH2O
********PEEP; Positive end-expiratory pressure
Predicting performance of risk factor for NIV failure in influenza infection with ARF
NIV failure group had lower PF ratio than NIV success group (168.7 vs 317.5; P = 0.001), higher SOFA score (6 vs 1; P = 0.001) and higher number infiltrated quadrant on chest radiography (2 vs 1; P = 0.001). Univariate analysis found SOFA score (OR = 2.275, 95% CI 1.809-2.861, P = 0.001), PF ratio level (OR = 6.385, 95% CI 3.649 – 11.172, p = 0.001) and number infiltrated quadrant on chest radiography (OR = 5.614, 95% CI 3.124 – 10.089, P = 0.001) as dependent risk factors for NIV failure (Table 2).
Multivariate analysis model identified SOFA score (OR = 2.163, 95% CI 1.577 – 2.968, P = 0.001) and number infiltrated quadrant on chest radiography (OR = 6.487, 95% CI 2.692 – 15.627, P = 0.001) as independent factors associated with NIV failure in influenza infection with ARF (Table 2).
Table 2. Univariate and multivariate analyses of NIV failure in influenza infection with ARF.
Factor analysis
|
***OR
|
P value
|
****aOR
|
P value
|
*SOFA score
|
2.275 (1.809-2.861)
|
0.001
|
2.163 (1.577 – 2.968)
|
0.001
|
**PF ratio level
|
6.385 (3.649 – 11.172)
|
0.001
|
2.053 (0.990 – 4.635)
|
0.083
|
Number infiltrated quadrant on chest radiography
|
5.614 (3.124 – 10.089)
|
0.001
|
6.487 (2.692 – 15.627)
|
0.001
|
***OR; odds ratio
****aOR; adjusted odds ratio; adjusted for neuromuscular disease patients, immunosuppression patients, SOFA score, PF ratio level, number infiltrated quadrant on chest radiography, tidal volume and initial PEEP.
*SOFA Score; Sequential Organ Failure Assessment Score
**PF ratio level; 0 = PF ratio > 200 mmHg with non-PEEP, 1 = PF ratio < 200 mmHg with non-PEEP or < 300 mmHg with PEEP > 5 cmH2O, 2 = PF ratio < 100 mmHg with non-PEEP or < 200 mmHg with PEEP > 5 cmH2O, 3 = PF ratio <100 mmHg with PEEP > 5 cmH2O
Hosmer–Lemeshow (X2) test was P value of 0.758.
SOFA score, PF ratio level and number infiltrated quadrant on chest radiography provided good ability to predict NIV failure in influenza infection with ARF by AUROC 0.894 (95% CI 0.839 - 0.948), 0.828 (95% CI 0.764 - 0.892) and 0.792 (0.721 – 0.863), respectively (Figure 1). We converted PF ratio level number infiltrated quadrant on chest radiography to rubric scales shown in Table 3. The cut-off points of predicting factors were SOFA score >4 (sensitivity 86.1%, specificity 84.1%; LR = 5.4), PF ratio level >2 (sensitivity 66.7%, specificity 86.4%; LR = 4.9) and number infiltrated quadrant on chest radiography >2 (sensitivity 50%, specificity 95.5%; LR =11.1).
Table 3. rubric scale for PF ratio and number infiltrated quadrant on chest radiography (PFCXR score)
Score
|
0
|
1
|
2
|
3
|
PF ratio
|
>200
|
< 200 with non-PEEP
or
< 300 with PEEP > 5
|
< 100 with non-PEEP
or
< 200 with PEEP > 5
|
<100 with PEEP > 5
|
Number quadrant infiltration on chest radiography
|
0
|
1
|
2
|
>3
|
Survival analysis: Probability of NIV success in 24-hour
Probability of NIV success by Kaplan-Meier curve, PF ratio level >2, number infiltrated quadrant on chest radiography >2, and SOFA score > 4 had low probability of NIV success in 24-hour than lower group, log rank P value of 0.017, 0.018 and 0.983, respectively (Figure 2).