Supplemental Material
Cerebro-Spinal Fluid Glucose and Lactate Levels after Subarachnoid Hemorrhage: a multicentre retrospective study
Fabio Silvio TACCONE
1, MD, PhD, Rafael BADENES
2, MD, PhD, Safa ARIB
1, MD, Francesca RUBULOTTA
3, MD, Sebastien MIREK
4, MD, Federico FRANCHI
1, MD, Sara GORDON
3, MD, Abdelouaïd NADJI
4, MD, Ilaria Alice CRIPPA
1, MD, Elena STASI
5, MD, Belaïd BOUHEMAD
4,
MD, Angels LOZANO ROIG
1,2, MD, Jacques CRETEUR
1, MD, PhD, Federico BILOTTA
5, MD
1Department of Intensive Care
Hopital Erasme, Brussels, Belgium, Université Libre de Bruxelles Brussels, Belgium
2Department of Anesthesiology and Intensive Care Hospital Clinic Universitari de Valencia
University of Valencia
3Department of Intensive Care
Charing Cross Hospital NHS trust, Imperial College London, UK
4Service d'Anesthésie Réanimation, CHU Dijon BP 77908, 21709 Dijon Cedex, France
5Department of Anesthesia and Intensive Care Sapienza University, Rome, Italy
Conflict of interest and Source of Funding: authors have disclosed that they do not have any conflicts of interest
Correspondence:
Pr. Fabio Silvio TACCONE Department of Intensive Care Erasme Hospital
Université Libre de Bruxelles (ULB) Route de Lennik, 808
1070 – Brussels (BELGIUM) email: [email protected] tel: +322 555 5587
fax: +322 555 4698
2
Definition of ICU events
The development of at least one infectious episode during the ICU stay was collected. Ventriculitis was defined as the identification of a microorganism from CSF by a Gram stain, culture of proximal EVD tip, the presence of fever (>38.0°C) and increased white cells into CSF (>6/mm3). Shock was defined as the requirement of vasopressors to maintain mean arterial pressure > 65 mmHg despite adequate fluid resuscitation for more than 6 hours, associated with increased blood lactate levels (>2 mmol/L) and organ dysfunction. Hyponatremia was defined as serum sodium levels <
135 mEq/L. The diagnosis of cerebral vasospasm was based on daily trans-cranial Doppler or angio-CT scan, according to local practices. The occurrence of convulsive or non-convulsive seizures after ICU admission was also collected. Hydrocephalus was identified according to radiological evaluation of cerebral CT-scans, which were performed according to the decisions of the attending physician. Patients were classified as poor-grade if the WFNS on admission was 4 or 5. A high Fisher grade was defined as a Fisher scale of 3 or 4.
3
Table 1. Characteristics of the study population, according to the ICU mortality and long-term neurological outcome (FO = favourable; UO = unfavourable).
Variable
All Patients (n=144)
Survivors (n=102)
Non-survivors (n=42)
FO (n=63)
UO (n=81)
Age, years 58 [49-66] 56 [47-64] 63 [52-71]* 54 [47-62] 60 [51-69] *
Male, n (%) 73 (51) 48 (47) 25 (60) * 32 (51) 41 (51)
COMORBID DISEASES
Heart disease, n (%) 33 (23) 18 (18) 15 (36) * 11 (17) 22 (27)
Hypertension, n (%) 65 (45) 46 (45) 19 (45) 22 (35) 43 (53) *
Diabetes, n (%) 31 (21) 20 (20) 11 (26) 10 (16) 21 (26)
COPD/asthma, n (%) 34 (24) 23 (22) 11 (26) 15 (24) 19 (23)
Chronic renal disease, n (%) 16 (11) 8 (8) 8 (19) 3 (5) 13 (16) *
Liver cirrhosis, n (%) 5 (3) 3 (3) 2 (5) 2 (3) 3 (4)
Cancer, n (%) 12 (8) 7 (7) 5 (12) 6 (9) 6 (7)
Immunosuppressive agents, n (%) 11 (8) 8 (8) 3 (7) 4 (6) 7 (9)
SAH CHARACTERISTICS
Time from admission to EVD, days 1 [0-3] 1 [0-2] 1 [0-4] 1 [0-6] 1 [0-3]
Aneurysm, n (%) 115 (80) 82 (80) 33 (79) 52 (82) 63 (78)
Endovascular therapy, n (%) 83 (58) 62 (61) 21 (50) 41 (65) 42 (52)
GCS on admission 10 [7-13] 11 [8-13] 7 [5-12] * 12 [8-14] 8 [6-12] *
WFNS score on admission 4 [3-4] 4 [2-4] 4 [3-5] * 3 [2-4] 4 [3-5] *
Fisher scale on admission 4 [3-4] 3 [3-4] 4 [3-4] * 3 [2-4] 4 [3-4] *
DURING ICU STAY
Vasospasm, n (%) 79 (55) 57 (56) 22 (52) 31 (49) 48 (59)
Hydrocephalus, n (%) 71 (49) 51 (50) 20 (28) 29 (46) 42 (52)
Intracranial hypertension, n (%) 83 (58) 53 (52) 30 (71) * 29 (46) 54 (67) *
Insulin therapy, n (%) 72 (50) 50 (49) 22 (52) 32 (51) 40 (49)
Infections, n (%) 68 (47) 48 (47) 20 (48) 26 (41) 42 (52)
Ventriculitis, n (%) 22 (15) 18 (18) 4 (9) 6 (9) 16 (20)
Shock, n (%) 41 (28) 24 (24) 17 (40) * 12 (19) 29 (36) *
Delayed neurological deficit, n (%) 36 (25) 27 (26) 9 (24) 8 (13) 28 (35)*
Seizures, n (%) 38 (26) 25(24) 13 (31) 12 (19) 26 (32)
Hyponatremia, n (%) 41 (28) 33 (32) 8 (19) 16 (25) 25 (31)
Fever, n (%) 73 (51) 55 (54) 18 (43) 28 (44) 45 (56)
OUTCOMES
ICU length of stay, days 12 [7-20] 14 [8-21] 8 [5-19] 12 [8-20] 12 [7-21]
ICU mortality, n (%) 42 (29) - 42 (100) - 42 (52)
UO at 3 months, n (%) 81 (56) 39 (38) 42 (100) - 81 (100)
COPD = chronic obstructive pulmonary disease; EVD = external ventricular drain; GCS = Glasgow coma scale; CT = computer tomography;
ICU = Intensive Care Unit;
* p < 0.05 survivors vs. non-survivors or FO vs. UO (univariate analysis)
Supplemental Table 2: Univariate analysis between data collected on the first day during insulin infusion therapy or not.
Insulin therapy
(n=72)
Non-Insulin therapy
(n=72)
p
CSF Glucose, mmol/L 4.9 [3.6-6.0] 4.5 [3.9-5.1] 0.102 CSF Lactate, mmol/L * 4.2 [3.0-7.0] 3.5 [2.7-4.5] 0.023 CSF Glucose/Lactate ratio * 1.2 [0.7-1.7] 1.3 [0.9-1.8] 0.557 Blood Glucose, mg/dl 179 [150-
222] 140 [118-155] <0.001 Blood Lactate, mmol/L 2.1 [1.2-3.6] 1.7 [1.2-2.1] 0.001 CSF/Blood Glucose ratio * 0.5 [0.3-0.6] 0.6 [0.5-0.7] 0.007 CSF/Blood Lactate ratio * 2.0 [1. 4-2.4] 2.2 [1.5-3.1] 0.173
CSF = cerebro-spinal fluid; * n=104 (n=63 on insulin therapy; n=41 not on insulin therapy)
Figure 1: Correlation between cerebrospinal fluid (CSF) and blood glucose (A) and lactate (B) concentrations.
Supplemental Figure 2: Distribution of CSF glucose levels to respect the blood glucose ranges in patients treated (upper) and not treated (lower) with insulin therapy.
Supplemental Figure 3: Receiver operating curve (ROC) for cerebrospinal glucose/lactate ratio (right, AUC 0.70 ([95% CI 0.60-0.80]; p<0.001) to predict long- term unfavourable outcome.