Background
Methods
Study design and setting
Characteristics of participants
Baseline clinical data collection
Sedation and analgesia
Neurological examination
Evoked potential (EP) assessment and analysis
Somatosensory evoked potentials (SSEP)
Brainstem auditory evoked potentials (BAEP)
Evoked potentials data analysis
Evoked potentials data | Healthy control subjects (n = 20) | Deeply sedated critically ill patients (n = 86) | ||
---|---|---|---|---|
Mean latency ± SD (in ms) | Mean latency + 2.5 SD (in ms) | Mean latency ± SD (in ms) | Delayed latency n (%) | |
SSEP components | ||||
N9 PL | 9.8 ± 0.6 | 11.4 | 11.0 ± 1.6 | 33 (38) |
N13 PL | 13.2 ± 0.8 | 15.2 | 14.9 ± 2.1 | 36 (42) |
P14 PL | 14.6 ± 0.9 | 16.8 | 16.2 ± 2.0 | 32 (37) |
N20 PLa
| 18.8 ± 1.0 | 21.4 | 21.6 ± 2.6 | 41 (48) |
N9-N13 IPL | 3.4 ± 0.4 | 4.4 | 3.9 ± 0.9 | 14 (16) |
P14-N20 IPLa
(ICCT) | 4.1 ± 0.5 | 5.3 | 5.3 ± 1.5 | 39 (45) |
BAEP components | ||||
Wave I PL | 1.5 ± 0.2 | 2.0 | 1.69 (0.31) | 13 (15) |
Wave III PL | 3.6 ± 0.2 | 4.1 | 3.96 (0.35) | 34 (40) |
Wave V PL | 5.6 ± 0.3 | 6.3 | 6.16 (0.61) | 34 (40) |
I–III IPL | 2.1 ± 0.2 | 2.6 | 2.28 (0.29) | 17 (20) |
III–V IPL (IPCT) | 2.0 ± 0.2 | 2.5 | 2.20 (0.45) | 15 (17) |
I–V IPL | 4.1 ± 0.3 | 4.8 | 4.51 (0.59) | 17 (20) |
Method for bias and confounding factors assessment
Outcome assessment
Statistical analysis
Results
Patients’ characteristics
Variables | All patients | Non-brain-injured patients | Brain-injured patients |
p value |
---|---|---|---|---|
Number of patients | 86 | 49 (57) | 37 (43) | |
Women—n (%) | 29 (34) | 15 (31) | 14 (38) | 0.50 |
Age (years)—mean ± SD | 61 ± 19 | 63 ± 16 | 58 ± 21 | 0.21 |
SAPS II at admission—median (IQR) | 48 (36 to 61) | 45 (30 to 61) | 50 (41 to 58) | 0.45 |
At the time of inclusion | ||||
Sepsis—n (%) | 56 (65) | 46 (94) | 10 (27) | <0.0001 |
RASS | −5 (−5 to −4) | −5 (−5 to −4) | −5 (−5 to −5) | 0.82 |
Use of sedation—n (%) | <0.0001 | |||
Synchronization with ventilator | 44 (51) | 33(67) | 11 (30) | |
Intracranial hypertension | 16 (19) | 0 (0) | 16 (43) | |
Others | 26 (30) | 16 (33) | 10 (27) | |
Sedative drug used | ||||
Midazolam—n (%) | 79 (92) | 48 (98) | 31 (84) | 0.02 |
Sufentanyl—n (%) | 79 (92) | 47 (96) | 32 (86) | 0.40 |
Propofol—n (%) | 9 (10) | 3 (6) | 6 (16) | 0.13 |
Total day-3 SOFA—median (IQR) | 11 (8 to 14) | 13 (10 to 15) | 10 (8 to 11) | 0.0006 |
Non-neurological day-3 SOFA—median (IQR) | 7 (5 to 10) | 9 (6 to 11) | 6 (4 to 7) | 0.052 |
Renal day-3 SOFA—median (IQR) | 0 (0 to 2) | 1 (0 to 3) | 0 (0 to 1) | 0.03 |
Liver day-3 SOFA—median (IQR) | 0 (0 to 1) | 0 (0 to 1) | 0 (0 to 0) | 0.19 |
Outcomes | ||||
Duration of sedation (days)—median (IQR) | 7 (4 to 14) | 7 (5 to 14) | 8 (4 to 12) | 0.48 |
Duration of mechanical ventilation (days)—median (IQR) | 15 (7 to 30) | 10 (6 to 34) | 18 (10 to 27) | 0.15 |
Delirium—n (%) | 35/61 (57) | 17/30 (57) | 18/31 (58) | >0.99 |
Delayed awakening—n (%) | 23/63 (37) | 7/32 (22) | 16/31 (52) | 0.02 |
Altered mental status—n (%) | 49/63 (78) | 21/31 (68) | 28/32 (88) | 0.07 |
In-ICU mortality—n (%) | 37/86 (43) | 24/49 (49) | 13/37 (35) | 0.19 |
Clinical and neurophysiological characteristics of the patients at inclusion
Variables | All patients | Non-brain-injured patients | Brain-injured patients |
p value |
---|---|---|---|---|
Number of patients | 86 | 49 (57) | 37 (43) | |
Glasgow Coma Score—median (IQR) | 3 (3 to 3) | 3 (3 to 3) | 3 (3 to 3) | 0.97 |
FOUR score—median (IQR) | 4 (2 to 5.7) | 4 (2 to 5.0) | 4 (2 to 5.5) | 0.73 |
Abolition of cough reflex | 24 (29) | 16 (33) | 8 (26) | 0.34 |
RASS—median (IQR) | −5 (−5 to −4) | −5 (−5 to −4) | −5 (−5 to −5) | 0.82 |
Delayed SSEP’s IPL—n (%) | ||||
N9–N13 IPL | 14 (16) | 11 (22) | 3 (8) | 0.08 |
P14–N20 IPLa (ICCT) | 39 (45) | 21 (43) | 18 (49) | 0.60 |
Delayed BAEP’s IPL—n (%) | ||||
I–III IPL | 17 (20) | 9 (18) | 8 (22) | 0.71 |
III–V IPL (IPCT) | 15 (17) | 9 (18) | 6 (16) | 0.80 |
I–V IPL | 17 (20) | 12 (24) | 5 (13) | 0.21 |
Comparisons of clinical and neurophysiological findings between the two subgroups of patients: brain-injured versus non-brain-injured group
Correlations between clinical, neurophysiological features, and in-ICU mortality
Variables | Survivors | Non-survivors |
p value | No altered mental status | Altered mental status |
p value |
---|---|---|---|---|---|---|
Number of patients—n (%) | 49 (57) | 37 (43) | 14 (22) | 49 (78) | ||
Age (years)—mean (SD) | 58 (18) | 64 (19) | 0.058 | 58 (20) | 60 (20) | 0.75 |
Women—n (%) | 19 (39) | 10 (27) | 0.36 | 5 (36) | 20 (41) | >0.99 |
SAPS II—median (IQR) | 48 (37 to 60) | 53 (34 to 70) | 0.47 | 45 (28 to 53) | 48 (37 to 59) | 0.36 |
Day-3 SOFA—median (IQR) | 10 (8 to 12) | 13 (10 to 17) | 0.004 | 10 (8 to 12) | 10 (8 to 13) | 0.96 |
GCS—median (IQR) | 3 (3 to 4) | 3 (3 to 3) | 0.18 | 3 (3 to 3) | 3 (3 to 5) | 0.29 |
FOUR Score—median (IQR) | 4 (3 to 6.5) | 4 (0 to 4.0) | 0.026 | 4 (3.2 to 5) | 4 (3 to 7) | 0.85 |
Abolition of cough reflex-n (%) | 7 (15) | 17 (47) | 0.003 | 3 (21) | 10 (22) | >0.99 |
RASSa—median (IQR) | −5 (−5 to −4) | −5 (−5 to −5) | 0.001 | −5 (−5 to −4) | −5 (−5 to −4) | 0.95 |
Brain injured—n (%) | 24 (49) | 13 (35) | 0.27 | 4 (29) | 28 (57) | 0.07 |
Sedative drug used | ||||||
Midazolam—n (%) | 44 (90) | 35 (95) | 0.43 | 13 (93) | 44 (90) | >0.99 |
Sufentanil—n (%) | 44 (90) | 35 (95) | 0.86 | 13 (93) | 44 (90) | >0.99 |
Propofol—n (%) | 9 (18) | 0 (0) | 0.009 | 0 (0) | 8 (16) | 0.18 |
Conduction times (ms)—mean (SD) | ||||||
SSEP N9–N13 IPL | 3.8 (0.9) | 4 (0.9) | 0.17 | 3.7 (0.6) | 3.9 (0.9) | >0.99 |
SSEP P14–N20 IPL (ICCT)a
| 5.2 (1.6) | 5.6 (1.5) | 0.02 | 5.1 (1.3) | 5.4 (1.6) | 0.64 |
BAEP I–III IPL | 2.2 (0.3) | 2.4 (0.3) | 0.09 | 2.3 (0.3) | 2.3 (0.3) | 0.81 |
BAEP III–V IPL (IPCT) | 2.2 (0.5) | 2.3 (0.4) | 0.33 | 2.0 (0.3) | 2.3 (0.5) | 0.001 |
Delayed conduction time—n (%) | ||||||
SSEP N9–N13 IPL | 7 (14) | 7 (19) | 0.57 | 1 (7) | 6 (12) | >0.99 |
SSEP P14–N20 IPL | 17 (35) | 22 (59) | 0.029 | 5 (36) | 22 (45) | 0.76 |
BAEP I–III IPL | 9 (18) | 8 (22) | 0.79 | 3 (21) | 7 (14) | 0.68 |
BAEP III–V IPL | 8 (16) | 7 (19) | 0.78 | 0 (0) | 12 (24) | 0.053 |
Correlations between clinical, neurophysiological features, and the occurrence of an altered mental status (AMS)
Discussion
Variables | All patients | SSEP’s P14–N20 (ICCT) | BAEP’s III–V (IPCT) | ||||
---|---|---|---|---|---|---|---|
Delayed | Non delayed | *p value | Delayed | Non delayed | *p value | ||
Number of patients—n (%) | 86 (100) | 39 (45) | 47 (55) | 15 (17) | 71 (83) | ||
RASS—median (IQR) | −5 (−5 to −4.2) | −5 (−5 to −5) | −5 (−5 to −4) | 0.003 | −5 (−5 to −4) | −5 (−5 to −5) | 0.45 |
Body temperature (°C)—mean (SD) | 36. (1.0) | 36.7 (1.0) | 36.4 (0.9) | 0.10 | 36.5 (1.1) | 36.6 (1.0) | 0.67 |
Sedative drugs used | |||||||
Midazolam—n (%) | 79 (92) | 36 (42) | 43 (50) | 0.89 | 14 (18) | 65 (82) | 0.82 |
Sufentanil—n (%) | 79 (92) | 37 (43) | 42 (49) | 0.36 | 15 (19) | 64 (81) | 0.21 |
Propofol—n (%) | 9 (10) | 2 (2) | 7 (8) | 0.14 | 1 (11) | 8 (89) | 0.60 |
Sedative drugs’ cumulative doses | |||||||
Midazolam (mg/kg)—median (IQR) | 5 (5 to 8) | 5 (5 to 9) | 5 (5 to 8) | 0.74 | 5 (4.2 to 9) | 5 (5 to 8) | 0.54 |
Sufentanil (µg/kg)—median (IQR) | 20 (10 to 30) | 20 (10 to 30) | 20 (10 to 30) | 0.70 | 20 (10 to 25) | 20 (10 to 30) | 0.63 |
Propofol (mg/kg)—median (IQR) | 10 (0 to 40) | 3 (1.5 to 6) | 20 (1.5 to 85) | 0.22 | 3 (3 to 3) | 15 (0 to 55) | 0.40 |
Abnormal brain imaging—n (%) | 34/59 (58) | 18/34 (53) | 16/34 (47) | 0.08 | 5/34 (15) | 29/34 (85) | 0.46 |
Focal brain injury—n (%) | 11 (32) | 6 (55) | 5 (45) | 0.96 | 1 (9) | 10 (91) | 0.72 |
Diffuse brain injury—n (%) | 23 (68) | 12 (52) | 11 (48) | 0.78 | 4 (17) | 19 (83) | 0.66 |