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Online Data Supplement
New insights in the weaning from mechanical ventilation: left ventricular diastolic dysfunction is a key player.
John Papanikolaou1, Demosthenes Makris1, Theodosios Saranteas2, Dimitrios Karakitsos3, Elias Zintzaras4, Andreas Karabinis3, Georgia Kostopanagiotou2, Epaminondas Zakynthinos1.
1Department of Critical Care, School of Medicine, University of Thessaly, University Hospital of Larissa, Thessaly, Greece
22nd Department of Anaesthesiology, School of Medicine, University of Athens, University Hospital of Athens ‘Attikon’, Athens, Greece
3Department of Critical Care, General State Hospital of Athens, Athens, Greece
4Department of Biomathematics, School of Medicine, University of Thessaly, Larissa, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, USA.
Methods
2-D Echocardiography
Conventional transthoracic 2-D echocardiographic examination was performed to assess LV internal dimensions, LV wall thickness and global LV/RV function, according to recommendations of American Society of Echocardiography [E1]. Right ventricular (RV) end-diastolic area (EDA)/end-systolic area (ESA) were measured for calculating right ventricular fractional area change [RVFAC(%)= 100*(RVEDA-RVESA)/RVEDA], and LVEDA for calculating RVEDA/LVEDA ratio. Left ventricular ejection fraction (LVEF) was estimated by using the Simpson’s modified method of disks.
LV mass was calculated as suggested by Devereux et al [E2] and indexed to body surface area.
Relative wall thickness (RWT) was measured at end-diastole, as: septal wall thickness + posterior wall thickness divided by LV diastolic diameter [E3].
Doppler Echocardiographic study
Baseline Doppler echocardiographic measurements were obtained before SBT initiation, while the patient was in pressure support ventilation (pre-SBT). Follow up measurements (end-SBT) in patients who succeeded in the trial, were collected 30 minutes after SBT initiation. In those who failed the procedure, measurements were obtained before reconnection to the ventilator.
Doppler echocardiography was performed from the apical 4-chamber view with an ultrasound device (Philips, XD11 XE, Andover, MA, U.S.A), equipped with the tissue Doppler imaging program and a phased array multifrequency transducer [E1]. Doppler signals were recorded along with the electrocardiogram and respiratory cycle waveform at a sweep speed of 100 mm/s and were digitally stored in the hardware for later analysis. Off-line analysis was carried out by an experienced cardiologist -EZ- blinded to patients’ identity and clinical status. Measurements were performed at end-expiration, in order to minimize the confounding effect of positive intrathoracic pressures on cardiac performance (at pre-SBT) and to obtain all DE measurements at the same time of the respiratoty cycle. The average of 3 end-expiratory cycles was used.
Mitral inflow curves were recorded as previously described [E4].The peak Doppler velocities of early (E) and late diastolic flow (A), the E-wave deceleration time (DTE) and the E/A ratio were measured.
Tissue Doppler Imaging (TDI) myocardial velocities were obtained from the apical 4-chamber view, as suggested [E4]. A 1.5-mm sample volume was placed sequentially at the lateral and septal mitral annulus, and subsequently at the lateral tricuspid annulus. Analysis was performed for the peak systolic (Sm), the early diastolic (Em), the late diastolic (Am) velocity and the Em/Am ratio at each site of interest, as well as for the average values of the lateral and septal mitral annular velocities (averaged Sm, Em, Am, Em/Am). The transmitral inflow E-wave to mitral annular Em ratios (lateral, septal or averaged E/Em values) were also calculated and analysed.
Left ventricular diastolic function was graded by means of DE, as previously suggested [E4]. Accordingly, our patients were classified as having i) normal diastolic function, ii) grade I (mild) diastolic dysfunction (impaired relaxation pattern) or iii) grade II to III (moderate to severe) diastolic dysfunction (pseudonormal or restrictive filling pattern, respectively).
Early flow propagation velocity (Vp) was measured from color M-mode recordings from apical 4-chamber view, by tracing the slope of the first “aliasing” velocity (red to blue) from the mitral valve plane to 4 cm distal into the left ventricular cavity [E4]. Analysis was also performed for the mitral inflow E velocity/Vp (E/Vp) ratio.
Results
Doppler Echocardiography
Table E1 shows basic clinical assessment (hemodynamic data, arterial blood gasses) and Doppler measurements performed before (pre-SBT) and at the end of a T-tube trial (end-SBT) in all 50 patients.
Heart rate and rate-pressure product (which is a global index of myocardial workload and oxygen demand) [E5] were increased by 7.9 and 11.3% (P<0.001 and P=0.002, respectively). PaO2, PaCO2 and pH were also significantly changed during SBT (P<0.001).
Transmitral velocities E and A were increased by 13.8 and 14.2% (P<0.001 and P=0.002, respectively) and DTE was reduced by 7.7% (P=0.002) in end-SBT compared to pre-SBT; E/A ratio was not significantly changed from baseline. The peak systolic velocity (Sm) at the tricuspid annulus as well as the early (Em) and late diastolic (Am) velocities at the septal mitral annulus were significantly increased (Δ%) between pre-SBT and end-SBT, by 21% (P=0.005), 7% (P=0.02), and 18% (P=0.028) respectively. Septal and averaged mitral E/Em were increased by 10.7% and 11.4% (P=0.043 and P=0.034, respectively); lateral E/Em increased but not significantly (P=0.1). E/Vp ratio did not manifest significant changes during SBT.
Table E1. Hemodynamic parameters and Doppler echocrardiographic measurements at baseline (pre-SBT) and at the end of a T-tube trial (end-SBT).
Basic hemodynamic parameters
Systolic BP (mmHg) / 142.5±3 / 146.1±4.1 / 2.7±2 / 0.22
Diastolic BP (mmHg) / 78.1±1.7 / 78.6±1.6 / 0.02±1.3 / 0.65
Mean BP (mmHg) / 99.6±1.9 / 100.5±2.1 / 1.1±1.2 / 0.49
Heart rate (beats/min) / 90.2±1.7 / 97.3±2.4 / 7.9±1.7 / <0.001**
Rate-pressure product
(beats/min* mmHg) / 12863±376 / 14453±689 / 11.3±3.3 / 0.002**
PaO2 (mmHg) / 117.3±4.3 / 88.6±1.9 / -21.2±2.3 / <0.001**
PaCO2 (mmHg) / 38.7±0.4 / 46.2±0.7 / 19.8±2.2 / <0.001**
Ph / 7.45±0.004 / 7.39±0.005 / -0.8±0.09 / <0.001**
Doppler parameters
Mitral inflow
E, cm/sec / 83.4±0.2 / 94.2±0.3 / 13.78±1.6 / <0.001**
A, cm/sec / 72.2±0.3 / 80.4±0.4 / 14.23±4.1 / 0.002**
“Conventional” Doppler echocardiographic markers of LV filling pressures
E/A / 1.252±0.006 / 1.288±0.007 / 4.50±3.4 / 0.439
DTE, msec / 199±6 / 180±5 / -7.68±2.7 / 0.002**
Lateral Mitral Annulus
Sm, cm/sec / 11.4±0.5 / 11.0±0.5 / -1.02±3.6 / 0.320
Em, cm/sec / 11.9±0.7 / 12.1±0.6 / 6.38±4.2 / 0.678
Am, cm/sec / 10.2±0.8 / 10.3±0.6 / 10.79±6.9 / 0.816
Em/Am / 1.37±0.15 / 1.33±0.12 / 7±7 / 0.648
Septal Mitral Annulus
Sm, cm/sec / 9.8±0.3 / 9.8±0.3 / 0.53±2.2 / 0.855
Em, cm/sec / 9.5±0.4 / 10.1±0.5 / 7.03±2.9 / 0.02*
Am, cm/sec / 8.9±0.6 / 10.1±0.5 / 18.06±6.2 / 0.028*
Em/Am / 1.23±0.12 / 1.11±0.11 / -2.6±7.8 / 0.220
Averaged (Lateral-Septal) Mitral Annulus
Sm, cm/sec / 10.6±0.3 / 10.4±0.4 / -0.8±2.4 / 0.325
Em, cm/sec / 10.7±0.5 / 11.1±0.5 / 5.29±2.6 / 0.179
Am, cm/sec / 9.6±0.6 / 10.2±0.5 / 12.76±5.5 / 0.167
Em/Am / 1.27±0.12 / 1.18±0.1 / 0.2±6.1 / 0.271
Tricuspid Annulus
Sm, cm/sec / 14.3±0.9 / 16.2±1.1 / 21.18±3.4 / 0.005**
Em, cm/sec / 11.8±1 / 11.2±1.1 / 9.89±6.1 / 0.553
Am, cm/sec / 14.8±1.4 / 16.1±1.7 / 20.42±7.8 / 0.287
Em/Am / 0.86±0.08 / 0.81±0.08 / -4±6 / 0.401
Color M-mode Doppler Velocity of Propagation
Vp, cm/sec / 59.6±2.9 / 65±3.9 / 10.33±4.3 / 0.057
Tei index / 0.552±0.195 / 0.563±0.034 / 7.18±5.25 / 0.708
“Advanced” Doppler echocardiographic markers of LV filling pressures
Lateral E/Em / 8.42±0.66 / 9.1±0.67 / 14.10±4.3 / 0.1
Septal E/Em / 9.84±0.58 / 10.72±0.71 / 10.74±3.9 / 0.043*
Averaged E/ Em / 8.87±0.58 / 9.6±0.64 / 11.44±3.2 / 0.034*
E/Vp / 1.58±0.08 / 1.72±0.15 / 45.12±13 / 0.203
Data are expressed as means ± SE. SBT= spontaneous breathing trial; BP= blood pressure; Rate-pressure product= heart rate x systolic blood pressure; PaO2=partial pressure of oxygen; PaCO2=partial pressure of carbon dioxide; E and A= Pulsed-wave Doppler early and late transmitral left ventricular filling wave velocity, respectively; LV= left ventricular; DTE= E–wave deceleration time; Sm, Em, Am = Tissue Doppler Imaging peak systolic, early and late diastolic velocity, respectively; Vp= color M-mode Doppler velocity of propagation; *P<0.05, paired t-test. **P<0.01, paired t-test.
Relationship between clinical/ echocardiographic parameters and weaning
Table E2. Univariate analysis of clinical variables at pre-SBT in patients according to weaning outcome. Continuous data are presented as mean (SE), categorical data are presented as n (%). Differences between groups were tested by 2 tests for proportions or 2-tailed t tests for mean values, as appropriate (a 2-tailed P value <0.05 was considered to be significant).
Success of Weaning(N=22) / Failure of Weaning
(N=28) / P
Age (years) / 43.2 (3.4) / 59.6 (3.2) / 0.001*
Sex (Male/Female) / 18 (82)/4 (18) / 15 (54)/ 13 (46) / 0.07
SBT (days from admission) / 18.1 (1.8) / 14.3 (1.9) / 0.15
APACHE II score (on admission) / 16.7 (0.7) / 18.5 (0.7) / 0.07
Tracheostomy tube / Orotracheal tube / 17 (77)/5 (23) / 19 (68)/9 (32) / 0.46
Hypertension / 6 (27) / 11 (39) / 0.37
Diabetes mellitus / 3 (14) / 6 (21) / 0.48
COPD patients / 5 (23) / 16 (57) / 0.014*
Neuro-critical patients / 14 (64) / 12 (43) / 0.14
Fluid balance (mean of 3days prior to SBT) (mL/day) / 5 (112) / 188 (108) / 0.25
Mean BP (mmHg) / 99.3 (2.8) / 99.9 (2.6) / 0.88
Heart rate (beats/min) / 86.7 (2.6) / 93 (2.2) / 0.07
Rate-pressure product
(beats/min* mmHg) / 12270 (536) / 13329 492) / 0.15
Temperature (˚C) / 37.2 (0.12) / 37.4 (0.09) / 0.35
f (breaths/min) / 19.3 (1.1) / 23.9 (1.1) / 0.007*
VE (L/min) / 9 (0.6) / 9.8 (0.5) / 0.27
PEEP (cmH2O) / 4.91 (0.06) / 4.96 (0.04) / 0.42
PS (cmH2O) / 12.7 (0.5) / 14.4 (0.4) / 0.006*
PFP (cmH2O*breaths/min) / 251 (21) / 342 (19) / 0.002*
f /VT (RSBI) / 45.2 (3.7) / 66.1 (4.7) / 0.002*
pH / 7.43 (0.006) / 7.46 (0.004) / 0.001*
PaO2 (mmHg) / 125 (7.4) / 111.3 (4.9) / 0.12
PaCO2(mmHg) / 38.6 (0.6) / 38.8 (0.5) / 0.82
PaO2/FIO2 ratio / 340 (19) / 284 (15.5) / 0.024*
SBT= spontaneous breathing trial; APACHE II= Acute Physiology and Chronic Health Evaluation Score II; COPD= chronic obstructive pulmonary disease; BP= blood pressure; Rate-pressure product= heart rate x systolic blood pressure; f= respiratory frequency under mechanical ventilation; VE= minute ventilation; PEEP= positive end-expiratory pressure; PS= level of pressure support; PFP= pressure frequency product (respiratory rate x level of pressure support); VT = mean tidal volume; RSBI= rapid shallow breathing index; PaO2=partial pressure of oxygen; PaCO2=partial pressure of carbon dioxide; FIO2=fraction of inspired oxygen.
Table E3. Univariate analysis of baseline (pre-SBT) Doppler echocardiographic variables according to SBT and weaning outcomes. Data are expressed as means ± SE.
Success
(N=27) / Failure
(N=23) / P / Success
(N=22) / Failure
(N=28) / P
Mitral inflow
E, cm/sec / 77±2 / 91±4 / 0.007** / 74±2 / 91±4 / 0.001**
A, cm/sec / 65±3 / 81±5 / 0.011* / 62±3 / 80±4 / 0.003**
“Conventional” Doppler surrogates of LV filling pressures
E/A / 1.26±0.07 / 1.24±0.12 / 0.9 / 1.26±0.08 / 1.244±0.1 / 0.89
DTE, msec / 203±5 / 194±10 / 0.387 / 205±5 / 194±9 / 0.31
TDI measurements
Lateral Mitral Annulus
Sm, cm/sec / 12.5±0.6 / 10±0.6 / 0.006** / 12.7±0.7 / 10.4±0.6 / 0.01**
Em, cm/sec / 13.7±0.8 / 9.8±0.9 / 0.003** / 14.5±0.9 / 9.8±0.8 / <0.001**
Am, cm/sec / 6.3±1.3 / 8.1±1 / 0.3 / 6.3±1.5 / 7.8±1 / 0.41
Em/Am / 1.59±0.24 / 1.19±0.17 / 0.169 / 1.75±0.27 / 1.15±0.15 / 0.046*
Septal Mitral Annulus
Sm, cm/sec / 10.7±0.4 / 8.7±0.3 / <0.001** / 10.7±0.5 / 9±0.4 / 0.004**
Em, cm/sec / 10.5±0.6 / 8.3±0.6 / 0.013* / 10.6±0.7 / 8.6±0.5 / 0.024*
Am, cm/sec / 9.3±0.9 / 8.6±0.7 / 0.587 / 8.8±0.8 / 9±0.8 / 0.92
Em/Am / 1.33±0.19 / 1.15±0.15 / 0.44 / 1.39±0.23 / 1.14±0.13 / 0.31
Averaged (Lateral-Septal) Mitral Annulus
Sm, cm/sec / 11.6±0.5 / 9.4±0.4 / 0.001** / 11.7±0.5 / 9.8±0.4 / 0.004**
Em, cm/sec / 12±0.6 / 9.2±0.7 / 0.004** / 12.6±0.7 / 9.3±0.6 / 0.001**
Am, cm/sec / 9.9±1 / 9.4±0.7 / 0.72 / 9.7±1.2 / 9.6±0.7 / 0.937
Em/Am / 1.45±0.21 / 1.12±0.14 / 0.19 / 1.55±0.24 / 1.1±0.12 / 0.07
Tricuspid Annulus
Sm, cm/sec / 15.4±1.1 / 12.9±1.4 / 0.154 / 15.5±1.3 / 13.3±1.2 / 0.223
Em, cm/sec / 6.1±1.4 / 9.7±1.4 / 0.091 / 6.2±1.7 / 9±1.3 / 0.191
Am, cm/sec / 7.8±1.9 / 12.1±1.9 / 0.116 / 7.5±2.2 / 11.6±1.7 / 0.129
Color M-mode Doppler Velocity of Propagation
Vp, cm/sec / 63±4 / 56±5 / 0.26 / 64±4 / 56±4 / 0.152
“Advanced” Doppler-derived surrogates of LV filling pressures
Lateral E/Em / 6.08±0.37 / 11.17±1.13 / <0.001** / 5.35±0.23 / 10.83±0.94 / <0.001**
Septal E/Em / 7.97±0.47 / 12.03±0.95 / <0.001** / 7.66±0.55 / 11.55±0.8 / <0.001**
Averaged E/ Em / 6.75±0.33 / 11.36±0.99 / <0.001** / 6.18±0.28 / 10.98±0.83 / <0.001**
E/Vp / 1.39±0.082 / 1.81±0.138 / 0.009** / 1.32±0.09 / 1.79±0.11 / 0.004**
SBT=spontaneous breathing trial; E and A= pulsed-wave Doppler early and late transmitral left ventricular filling wave velocity, respectively; LV= left ventricular; DTE= E–wave deceleration time; TDI= Tissue Doppler Imaging; Sm, Em, Am = TDI-derived peak systolic, early and late diastolic velocity, respectively; Vp= color M-mode Doppler velocity of propagation. *P<0.05, **P<0.01, 2-tailed t test for mean values.
Table E4. Univariate analysis of alterations (Δ%) of clinical and Doppler echocardiographic variables recorded during SBT according to SBT and weaning outcomes. Data were expressed as means±SE. Differences between groups were tested by 2-tailed t tests for mean values (a 2-tailed P value <0.05 was considered to be significant).
(Δ%) / SBT / Weaning
Success
(N=27) / Failure
(N=23) / P / Success
(N=22) / Failure
(N=28) / P
Clinical parameters
PaO2 / -17.3±3.2 / -25.8±3.3 / 0.07 / -17.4±3.6 / -24.1±3 / 0.159
PaCO2 / 10.8±2.1 / 30.3±2.8 / <0.001 / 8.2±2 / 28.9±2.5 / <0.001
pH / -0.43±0.09 / -1.25±0.11 / <0.001 / -0.31±0.08 / -1.2±0.01 / <0.001
Systolic BP (mmHg) / -1.8±2.6 / 7.9±2.6 / 0.012 / -5.2±2.1 / 8.9±2.6 / <0.001
Diastolic BP (mmHg) / -1.8±1.3 / 2.2±2.4 / 0.13 / -2.7±1.4 / 2.1±2.1 / 0.074
Mean BP (mmHg) / -2±1.5 / 4.8±1.7 / 0.004 / -4±1.3 / 5.1±1.5 / <0.001
Heart rate (beats/min) / 4±1.9 / 12.3±2.9 / 0.016 / 2.2±1.7 / 12.3±2.5 / 0.003
Rate-pressure product
(beats/min* mmHg) / 2.5±3.8 / 21.6±4.8 / 0.003 / -3.2±2.2 / 22.7±4.5 / <0.001
Doppler parameters
Mitral inflow analysis
E / 14±2.1 / 13.6±2.4 / 0.91 / 13.5±2.4 / 14±2.1 / 0.9
A / 17.3±4.4 / 10.7±7.2 / 0.42 / 18.2±5 / 11.2±6 / 0.39
“Conventional” Doppler markers of LV filling pressures
E/A / -0.2±3.3 / 10±6.2 / 0.14 / -1±3.9 / 8.8±5.2 / 0.16
DTE / -10.3±3.3 / -4.6±4.6 / 0.31 / -12.6±3.6 / -3.8±4 / 0.12
TDI parameters
Lateral Sm / -1.7±4.1 / -0.2±6.3 / 0.83 / -5±3.7 / 2.1±5.7 / 0.33
Lateral Em / 7±5.3 / 5.6±6.9 / 0.88 / 0.3±2.8 / 11.2±7.2 / 0.2
Septal Sm / -1.3±3 / 2.7±3.3 / 0.37 / -2.1±3.3 / 2.6±3 / 0.3
Septal Em / 6.3±3.3 / 7.9±5.2 / 0.79 / 8.4±3.7 / 5.9±4.4 / 0.68
Averaged Sm / -2.2±3 / 0.8±3.8 / 0.54 / -4.2±3.1 / 1.9±3.5 / 0.21
Averaged Em / 5.3±2.5 / 5.3±5 / 1 / 3.2±2.2 / 7±4.4 / 0.48
Right ventricular Sm / 20±4 / 17±5 / 0.64 / 18.4±4.6 / 18.8±4.4 / 0.95
Right ventricular Em / 6±6 / 10±7.7 / 0.74 / 2.5±7.2 / 10.9±6.7 / 0.44
Color M-mode Doppler Velocity of Propagation
Vp / 11.4±4.6 / 10±8.3 / 0.88 / 12.1±5.5 / 9.7±6.8 / 0.79
“Advanced” Doppler markers of LV filling pressures
Lateral E/Em / 10.7±4 / 18.1±8.2 / 0.4 / 14.7±3.5 / 13.6±7.3 / 0.9
Septal E/Em / 10.6±4.4 / 11.8±7.2 / 0.89 / 7.8±4.7 / 13.6±6.1 / 0.49
Averaged E/ Em / 9.9±3 / 13.7±6.3 / 0.57 / 11.4±3 / 11.9±5.4 / 0.95
E/Vp / 4.8±6 / 14.8±8 / 0.31 / 3.9±7.1 / 13.7±6.7 / 0.32
SBT= spontaneous breathing trial; SE= standard error; PaO2=partial pressure of oxygen; PaCO2=partial pressure of carbon dioxide; Rate-pressure product= heart rate xsystolic blood pressure; E and A= Pulsed-wave Doppler early and late transmitral left ventricular filling wave velocity, respectively; LV= left ventricular; DTE= E–wave deceleration time; TDI= tissue Doppler Imaging; Sm, Em, Am = TDI-derived peak systolic, early and late diastolic velocity, respectively; Vp= color M-mode flow propagation velocity.
Table E5. Diagnostic performance of baseline clinical characteristics and cardiac Doppler parameters in predicting SBT failure.