Yvonnick Blanloeil

Background: Singlet oxygen (¹O₂) oxidizes targets through the production of secondary reactive oxygen species (SOS). Cancers induce oxidative stress changing with progression, the resulting antioxidant status differing from one patient to the other. The aim of this study was to determine the oxidative status of patients with resectable Non-Small cell lung cancers (NSCLC) and the potential influence of antioxidants, compared to sera from healthy donors. Materials and Methods: Serum samples from 10 women and 28 men, 19 adenocarcinomas (ADK), 15 patients N1 or M1 were submitted to a photoreaction producing ¹O₂. Then, samples were supplemented with vitamins (Vit C, Vit E), or glutathione (GSH). Results: Squamous cell carcinomas (SCC) and metastatic SCCs induced a lower SOS rate. While Vit C increased SOS in controls as in patients with metastases, Vit E or the combination of Vit E and C strongly reduced SOS. GSH alone lightly decreased SOS in controls but had no effect in patients either alone or combined with Vit C. Conclusion: In “early” lung cancers, SOS are comparable or lower than for healthy persons. The role of Vitamins varies with gender, cancer type, and metastases. This suggests that an eventual supplementation should be performed on a per-patient basis to evidence any effect.

Stress cardiomyopathy is a common life-threatening complication after aneurysmal subarachnoid hemorrhage (SAH). We hypothesized that left ventricular (LV) longitudinal strain alterations assessed with speckle tracking could identify early systolic function impairment. This was an observational single-center prospective pilot controlled study conducted in a neuro-intensive care unit. Forty-six patients with severe SAH with a World Federation of Neurological Surgeons grade (WFNS) ≥III were included. Transthoracic echocardiography (TTE) was performed on day 1, day 3, and day 7 after the patient’s admission. A cardiologist blinded to the patient’s management analyzed the LV global longitudinal strain (GLS). The control group comprised normal subjects matched according to gender and age. On day 1 median (25th–75th percentile) GLS was clearly impaired in SAH patients compared to controls [−16.7 (−18.7/−13.7) % versus −20 (−22/−19) %, p < 0.0001], whereas LVEF was preserved [65 (59−70) %]. GLS was severely impaired in patients with a WFNS score of V versus III–IV [−15.6 (−16.9/−12.3) % versus −17.8 (−20.6/−15.8) %, p = 0.008]. Seventeen (37 %) patients had a severe GLS alteration (>−16 %). In these patients, GLS improved from day 1 [−12.4 (−14.8/−10.9) %] to last evaluation [−16.2 (−19/−14.6) %, p = 0.0007] in agreement with the natural evolution of stress cardiomyopathy. On the basis of LV GLS assessment, we demonstrated for the first time that myocardial alteration compatible with a stress cardiomyopathy is detectable in up to 37 % of patients with severe SAH while LVEF is preserved. GLS could be used for sensitive detection of stress cardiomyopathy. This is critical because cardiac impairment remains a major cause of morbidity and mortality after SAH.

Introduction: Hyperglycemia is a marker of poor prognosis in severe brain injuries. There is currently little data regarding the effects of intensive insulin therapy (IIT) on neurological recovery. Methods: A sub-group analysis of the randomized-controlled CGAO-REA study (NCT01002482) in surgical intensive care units (ICU) of two university hospitals. Patients with severe brain injury, with an expected ICU length of stay ≥48 hours were included. Patients were randomized between a conventional glucose management group (blood glucose target between 5.5 and 9 mmol.L⁻¹) and an IIT group (blood glucose target between 4.4 and 6 mmol.L⁻¹). The primary outcome was the day-90 neurological outcome evaluated with the Glasgow outcome scale. Results: A total of 188 patients were included in this analysis. In total 98 (52%) patients were randomized in the control group and 90 (48%) in the IIT group. The mean Glasgow coma score at baseline was 7 (±4). Patients in the IIT group received more insulin (130 (68 to 251) IU versus 74 (13 to 165) IU in the control group, P = 0.01), had a significantly lower morning blood glucose level (5.9 (5.1 to 6.7) mmol.L⁻¹ versus 6.5 (5.6 to 7.2) mmol.L⁻¹, P P P = 0.4). There were no differences in day-28 mortality. The occurrence of hypoglycemia did not influence the outcome. Conclusions: In this sub-group analysis of a large multicenter randomized trial, IIT did not appear to alter the day-90 neurological outcome or ICU morbidity in severe brain injured patients or ICU morbidity.

Ventilator-acquired pneumonia (VAP) is a common burden in intensive care unit (ICU) patients, but, to date, specific data are not available in patients with severe aneurysmal subarachnoid hemorrhage (SAH). A single neuro-ICU retrospective analysis of 193 patients with SAH requiring mechanical ventilation (MV) ≥48 h admitted from January 2005 to May 2010 was undertaken. The diagnosis of early VAP was prospectively upheld during a multidisciplinary staff meeting, according to the American Thoracic Society (ATS) 2005 guidelines with a threshold of 7 days after the onset of MV. Patients had a median age of 53 (44–62) years and 70 (36 %) were male. The median Glasgow coma scale (GCS) score before MV was 9 (5–14). 142 (74 %) patients had a World Federation of Neurosurgeons (WFNS) score ≥III. Aneurysm was secured with an endovascular coiling procedure in 162 (84 %) patients. 81 (48.7 %) patients declared an early VAP. On multivariate analysis, male sex (odds ratio [OR] 2.26, 95 % confidence interval [CI] [1.14–4.46]), use of mannitol before day 7 (OR 3.03, 95 % CI [1.54–5.95]), and achieving enteral nutrition ≥20 kcal kg⁻¹ day⁻¹ after day 7 (OR 2.91, 95 % CI [1.27–6.67]) remained independent risk factors of VAP. The main pathogens involved were methicillin-susceptible Staphylococcus aureus (MSSA) (34.9 %), Haemophilus influenzae (28.1 %), Streptococcus pneumoniae (15.5 %), and Enterobacteriaceae (10.7 %). Early VAP was associated with a longer duration of MV and ICU stay, but not with an excess of mortality. Early VAP bears significant morbidity in patients with severe SAH. Pathogens involved in early VAP are susceptible to antibiotics. Among modifiable risk factors of VAP, early enteral nutrition could be an easy and effective target.

For decades thiopental has been considered as the hypnotic drug of choice for intracranial surgery. However, total intravenous anesthesia performed with thiopental is associated with delayed recovery, whereas early post-operative neurological evaluation is critical. For this reason, target controlled infusion (TCI) of propofol is increasingly used for maintenance of anesthesia. However, a thiopental TCI has never been assessed for this purpose. We tested the hypothesis that a thiopental TCI provides an acceptable way to achieve early recovery compared to a propofol TCI during supratentorial surgery. Eighty patients undergoing elective craniotomy for a supratentorial tumor were randomized to receive either a propofol TCI (group P) or a thiopental TCI (group T). Both groups received a sufentanil TCI and the bispectral index was monitored. The primary end-point was time to tracheal extubation. Secondary end-points were per- and post-operative hemodynamics as well as respiratory and recovery parameters. Assessment of study end-points was performed by an intensive care specialist blinded (like the patient) to the received hypnotic. Time to extubation was significantly (P<0.0001) shorter in group P (median 149 minutes; interquartile range 72-250 minutes) than in group T (median 453 minutes; interquartile range 286-813 minutes). Similarly, the recovery parameters were significantly better in group P than in group T. There was no difference between groups in terms of patient characteristics and hemodynamic parameters. Even with TCI and bispectral index monitoring, thiopental is associated with an inappropriate delayed recovery from supratentorial surgery compared to propofol TCI.

Introduction: We sought to investigate whether the use of balanced solutions reduces the incidence of hyperchloraemic acidosis without increasing the risk for intracranial hypertension in patients with severe brain injury. Methods: We conducted a single-centre, two-arm, randomised, double-blind, pilot controlled trial in Nantes, France. Patients with severe traumatic brain injury (Glasgow Coma Scale score ≤8) or subarachnoid haemorrhage (World Federation of Neurosurgical Society grade III or higher) who were mechanically ventilated were randomised within the first 12 hours after brain injury to receive either isotonic balanced solutions (crystalloid and hydroxyethyl starch; balanced group) or isotonic sodium chloride solutions (crystalloid and hydroxyethyl starch; saline group) for 48 hours. The primary endpoint was the occurrence of hyperchloraemic metabolic acidosis within 48 hours. Results: Forty-two patients were included, of whom one patient in each group was excluded (one consent withdrawn and one use of forbidden therapy). Nineteen patients (95%) in the saline group and thirteen (65%) in the balanced group presented with hyperchloraemic acidosis within the first 48 hours (hazard ratio = 0.28, 95% confidence interval [CI] = 0.11 to 0.70; P = 0.006). In the saline group, pH (P = .004) and strong ion deficit (P = 0.047) were lower and chloraemia was higher (P = 0.002) than in the balanced group. Intracranial pressure was not different between the study groups (mean difference 4 mmHg [-1;8]; P = 0.088). Seven patients (35%) in the saline group and eight (40%) in the balanced group developed intracranial hypertension (P = 0.744). Three patients (14%) in the saline group and five (25%) in the balanced group died (P = 0.387). Conclusions: This study provides evidence that balanced solutions reduce the incidence of hyperchloraemic acidosis in brain-injured patients compared to saline solutions. Even if the study was not powered sufficiently for this endpoint, intracranial pressure did not appear different between groups. Trial registration: EudraCT 2008-004153-15 andNCT00847977 The work in this trial was performed at Nantes University Hospital in Nantes, France.

Prevention of vasospasm is a challenging issue in subarachnoid hemorrhage (SAH) patients and the objective is to compare high dobutamine-induced cardiac index (CI) and high norepinephrine-induced hypertension for the prevention of vasospasm in SAH patients. Single center, single blind, controlled randomized study. Patients hospitalized in intensive care unit (ICU) for a moderate to severe SAH (WFNS grade ≥2) were randomized to receive dobutamine to reach a 25 % increase in cardiac index or norepinephrine to reach a mean arterial pressure ≥100 mmHg. Norepinephrine could be used in the dobutamine group to maintain a cerebral pressure perfusion ≥60 mmHg. Primary endpoint was the incidence of angiographic vasospasm in the first 14 days in the ICU setting, which was upheld by a cerebral arteriography. Secondary endpoints were the incidence of delayed ischemic deficits, duration of mechanical ventilation, and ICU length of stay (LOS). During the 3-year study, 41 patients were randomized. Six patients were excluded—3 because of consent withdrawal and 3 who did not receive the assigned treatment. Respectively, 17 and 18 patients in the dobutamine and the norepinephrine group were kept in analysis. Five (28 %) patients in the dobutamine group and 5 (27 %) patients in the norepinephrine group developed vasospasm in ICU (p = 1). Seven (41 %) patients presented a delayed ischemic deficit in the dobutamine group and 9 (50 %) in the norepinephrine group (p = 0.24). Duration of mechanical ventilation was 8 [0.5–11.5] days in the dobutamine group and 19 [2.7–23] days in the norepinephrine group (p = 0.01). ICU LOS was 11 [6–15] days in the dobutamine group and 21 [9–28] days in the norepinephrine group (p = 0.01). As compared to norepinephrine-induced hypertension, dobutamine-induced high CI did not reduce the rate of vasospasm in SAH patients. Dobutamine may reduce durations of mechanical ventilation and ICU LOS.