Fifty-three PEEP titrations were performed in the prone (n = 29) and supine (n = 24) positions. In twelve (75%) patients the measurements were performed in supine and prone positions within 15 min of position change, and for 6 patients (38%) the measurements were done repeatedly at 12-hour intervals until the 5th day after the ICU admission. Four (25%) patients had the PaO2:FiO2 ratio 100 – 200 and 12 (75%) had PaO2:FiO2 ratio < 100. Baseline patient characteristics are shown in Table 1.
Table 1
Baseline characteristics of patients in the first 24 hours of ICU admission due to COVID-19.
Demographic data
|
n = 16
|
Age (years), mean (SD)
|
56 (12)
|
Male, n (%)
|
12 (75%)
|
Female, n (%)
|
4 (25%)
|
Body mass index (kg.m-2), mean (SD)
|
33 (7)
|
Scoring systems on admission
|
|
APACHE II score, median (IQR)
|
13 [12-19]
|
SOFA score, median (IQR)
|
7 [5-9]
|
PaO2/FIO2 ratio, mean (SD)
|
74 (31)
|
Medical History, n (%)
|
|
Hypertension
|
10 (62%)
|
Diabetes
|
8 (50%)
|
Chronic heart failure
|
5 (31%)
|
Chronic kidney disease
|
3 (18%)
|
Chronic obstructive pulmonary disease / Asthma
|
1 (6%)
|
Smoking
|
5 (30%)
|
Autoimmune
|
1 (6%)
|
Others a
|
4 (25%)
|
Adjunctive therapies, n (%)
|
|
Prone position
|
14 (87%)
|
Neuromuscular blocking agents
|
15 (94%)
|
Corticosteroids for COVID-19 b
|
16 (100%)
|
Veno-venous extracorporeal membrane oxygenation
|
2 (12%)
|
Continuous renal replacement therapy
|
7 (43%)
|
Outcomes, median (IQR)
|
|
Duration of mechanical ventilation (days)
|
11 [7,36]
|
ICU length of stay (days)
|
14 [9,47]
|
30-day mortality (n, %)
|
4 (25%)
|
SD – standard deviation, n – number, APACHE II – acute physiology and chronic health evaluation 2, IQR – interquartile range, SOFA score – sequential organ failure assessment score, PaO2 – partial pressure of oxygen in arterial blood. a Other includes endocrine disorders, neurologic disorders, chronic liver disease, b dexamethasone 8 mg per day while on mechanical ventilation.
From the 53 PEEP versus TauE plots obtained, 40 (75%) were recruitable and 13 (25%) nonrecruitable (Table 2). PEEP values within 5% of the TauEMAX were, considered to be in the ‘optimal PEEP range’ and are indicated by colored boxes on the plots (Figure 1 and Figure 2).
Table 2
Pattern groups based on positive end-expiratory pressure (PEEP) versus TauE
GROUP
|
DEFINITION
|
n (%)
|
RECRUITABLE
|
TauE shows evidence of recruitment (increase in TauE, or no significant change in TauE with increasing PEEP using constant inspiratory pressure) (Fig. 1a)
|
40 (75%)
|
NONRECRUITABLE
|
TauE did not show evidence of recruitment (decrease in TauE with increasing PEEP using constant inspiratory pressure) (Fig. 1b)
|
13 (25%)
|
n – number of PEEP titrations, TauE – expiratory time constant, PEEP – positive end-expiratory pressure
Measurements of optimal PEEP and optimal PEEP range using TauE are shown in Table 3. The recruitable group showed significantly higher optimal PEEP than the nonrecruitable group (p < 0.001). The comparison of Vte, PEEP and PEEP ranges for supine and prone positions are shown in Table 4. The optimal PEEP was higher and the Vte lower in the supine position when compared to the prone position for recruitable patterns: p < 0.001 and p = 0.26, respectively. The width of the optimal PEEP range was not significantly different (p = 0.09) between the two patient positions. For the non-recruitable patterns there was no difference in optimal PEEP, PEEP range and Vte between the supine and prone positions: p = 0.47, p = 0.82, and p = 0.48, respectively.
Table 3
Analysis of all 53 PEEP titrations using TauE
|
RECRUITABLE
|
NON-RECRUITABLE
|
p values
|
n
|
40
|
13
|
N/A
|
Vte (ml/kg/PBW)
|
8.4 (1.2)
|
8.0 (1.1)
|
0.29
|
PEEP (cmH2O) *
|
9 (3.5)
|
4 (3.5)
|
0.001
|
PEEP range size (cmH2O) *
|
6 – 11
|
1 – 7
|
0.091
|
Analysis of all 53 PEEP titrations showing the optimal PEEP and optimal PEEP range using the expiratory time constant (TauE). Standard deviations are shown in parenthesis. *optimal PEEP based on maximum TauE (TauEMAX) **optimal PEEP range based on maximum TauE (TauEMAX) ± 5%. n – number, N/A – not applicable, Vte – expiratory tidal volume, PBW – predicted body weight.
Table 4
Analysis of all 53 PEEP titrations using TauE in different positions
|
PRONE POSITION
n = 29
|
SUPINE POSITION
n = 24
|
|
Recruitable
|
Non-recruitable
|
Recruitable
|
Non-recruitable
|
n
|
21
|
8
|
19
|
5
|
Vte (ml.kg-1 of PBW)
|
9.2 (1.3)
|
7.9 (1.2)
|
7.6 (1.1)
|
8.4 (1.2)
|
PEEP (cmH2O) *
|
8 (3)
|
4 (4)
|
9 (4)
|
5 (3)
|
PEEP range size (cmH2O) **
|
6 - 10
|
1 - 8
|
7 - 12
|
1 – 7
|
Analysis of 53 positive end-expiratory pressure (PEEP) titrations showing the optimal PEEP and optimal PEEP range using the expiratory time constant (TauE) in different patient positions. Standard deviations are shown in parenthesis. * optimal PEEP based on the highest TauE (TauEMAX), ** optimal PEEP range based on TauEMAX ± 5%. n – number, Vte – expiratory tidal volume, PBW – predicted body weight.
Comparison of optimal PEEP levels as determined by TauE versus compliance
For comparison to traditional methods of PEEP titration, we compared the optimal PEEP and optimal PEEP range using CRS in the same way as using TauE method (Table 5). There was no difference in the mean optimal PEEP between TauE method and CRS method (p < 0.09). However, in the recruitable group, the optimal PEEP range was significantly wider with CRS than with TauE method, both for prone (p = 0.016) and supine (p = 0.02) positions. In the nonrecruitable group, the width of the PEEP range based on CRS was wider but not statistically significant in the prone (p = 0.19) or supine positions (p = 0.24).
Table 5
Comparison of TauE vs Compliance
|
PRONE POSITION
n = 29
|
SUPINE POSITION
n = 24
|
|
Recruitable
|
Non-recruitable
|
Recruitable
|
Non-recruitable
|
n
|
21
|
8
|
19
|
5
|
PEEP TauE (cmH2O)
|
8 (3)
|
4 (4)
|
9 (4)
|
5 (3)
|
PEEP CRS (cmH2O)
|
7 (2)
|
5 (4)
|
11 (4)
|
5 (2)
|
PEEP Range TauE (cmH2O)
|
6 - 10
|
1 - 8
|
7 - 12
|
1 – 7
|
PEEP Range CRS (cmH2O)
|
5 - 14
|
0 - 11
|
6 - 15
|
0 - 10
|
Comparison of the optimal positive end-expiratory pressure (PEEP) and optimal PEEP range using the maximum expiratory time constant (TauE) or the highest compliance (CRS). Optimal PEEP range was identified as maximum TauE (TauEMAX) ± 5% or maximum CRS ± 5%. Standard deviations are shown in parenthesis. n – number, PEEP – positive end-expiratory pressure, TauEMAX – maximum expiratory time constant, CRS – dynamic compliance.
We also correlated the CRS with TauE at all PEEP levels (Figure 3) showing moderate positive correlation (r2 = 0.43, p < 0.001 for TauE vs CRS). However, we also found there was high individual variation when assessing optimal PEEP using TauE and optimal PEEP using CRS.