Assessment of Bacterial Colonization of Intracranial Pressure Transducers: A Prospective Study.

OBJECTIVES: Cerebral infections related to the presence of an intraparenchymal intracranial pressure transducer (ICPT) are rare. We assessed the incidence of ICPT-related infections and colonization using culture, molecular biology, and electron microscopy. METHODS: All consecutive patients in a neurosurgical intensive care unit who had an ICPT inserted between March 2017 and February 2018 were prospectively included. Presence of colonization on the ICPTs was assessed after removal using culture, scanning electron microscopy (SEM), and next-generation sequencing (NGS). RESULTS: Fifty-three ICPTs (53 patients), indwelling for a median of 4 (range 3-7) days, were studied. Median patient follow-up was 3 months. SEM, microbial culture, and NGS were performed for 91%, 79%, and 72% of ICPTs, respectively; 28 ICPTs (53%) were assessed using all three techniques. No patient developed ICPT-related infection. Microbial cultures were positive for two of the ICPTs (5%); colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was observed on 35/48 (73%) of ICPTs. A median of 10 (8-12) operational taxonomic units were identified for each ICPT, most being of environmental origin. There was no association between biofilm maturity and antimicrobial treatment or duration of ICPT insertion. Antimicrobial treatment was associated with decreased alpha and beta-diversity (p = 0.01). CONCLUSIONS: We observed no ICPT-related cerebral infections although colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was the main bacterial lifestyle on the ICPTs.

Natural history of ventriculostomy-related infection under appropriate treatment and risk factors of poor outcome: a retrospective study.

OBJECTIVEThe authors aimed to describe the natural history of ventriculostomy-related infections (VRIs) under appropriate treatment and to assess risk factors for poor outcome.METHODSAll patients older than 18 years in whom an external ventricular drain (EVD) had been implanted and who had developed a VRI requiring treatment were included in this retrospective study. D0 was defined as the first day of antibiotic administration. Clinical and biological parameters were compared each day beginning with D1 and ending with D10 to those of D0. The authors defined D0 in a control group as the day a CSF culture came back positive, without any sign of infection. The authors then searched for poor prognostic factors in the VRI group.RESULTSAmong 567 patients requiring an EVD between January 2007 and October 2017, 39 developed a VRI. Most were monomicrobial infections, and 47 microbes were responsible (45% were gram-positive cocci). Clinical parameters differed significantly from the control group during the first 2 days and then returned to baseline. The CSF parameters differed significantly from the control group for a longer period, returning to baseline after 5 days. CSF sterilization occurred in a median time of 2 days. An intrathecal route or EVD exchange was not associated with a poor outcome. No clinical or biological parameter between D3 and D5 was linked to outcome.CONCLUSIONSClinical status improved faster than CSF parameters (before and after D5, respectively). Some CSF parameters remained abnormal until D10. Body temperature and microbiological cultures normalized faster than other parameters.

The multistep road to ventilator-associated lung abscess: A retrospective study of S.aureus ventilator-associated pneumonia.

OBJECT: We observed some cases of lung abscess (LA) in ICU patients suffering S.aureus ventilator-associated pneumonia (S.aureus-VAP). We aimed to assess which of the host and/or bacteria-related features are associated with LA. METHODS: We conducted a retrospective study from January 2009 to July 2013 in a trauma surgical ICU within a teaching hospital. All adult patients presenting with S.aureus-VAP were included. We compared two groups of patients according to the formation or not of LA concomitantly to S.aureus-VAP. RESULTS: Seventy-nine S.aureus-VAP patients, predominantly males (85%) of rather young age (mean [SD]: 35yr [21-64]) with severe trauma (initial Simplified Acute Score II = 42 [32-52]) related-ICU admission, were included. Among them, 10 (14%) developed LA. Patient's characteristics significantly associated with LA development were: a younger age (p = 0.003), road traffic accidents admission (p = 0.017), head injury (p = 0.002), lower Glasgow Coma Scale (p = 0.009), blunt chest trauma (p = 0.01) pneumothorax (p = 0.01) and lung contusions (p = 0.002). No microbiological factors were significantly associated with LA formation. Abscesses were mostly bilateral, ≥5 cm of diameter and with a posterior location. CONCLUSIONS: Our results do not favor a specific virulence of S.aureus, but rather highlight the role of multiple insults to the lung, promoting LA formation. Despite a similar severity score, patients with LA had more serious trauma, combining severe both chest and head insults.

Secondary Insults and Adverse Events During Intrahospital Transport of Severe Traumatic Brain-Injured Patients.

BACKGROUND: Our aim was to assess the occurrence of secondary insults (SIs) or adverse events (AEs) during intrahospital transport (IHT) of severe traumatic brain injury (TBI) patients for head computed tomography (CT) scanning. METHODS: A prospective study based on severe TBI patients admitted from June 2011 through June 2013 in a level I trauma center. Patients received an IHT to perform a control CT scan in the first 3 days following trauma. The occurrence of SIs and AEs was assessed during the IHT for a control CT scan. The frequency of SIs was compared to the periods "before," "during," and "after" IHT. SI was defined by an intracranial pressure (ICP) >30 mmHg, a cerebral perfusion pressure (CPP) <50 mmHg, systolic blood pressure (SBP) <90 mmHg, or saturation pulse O2 (SpO2) <90 % for more than five consecutive minutes. An AE was defined as failures of hardware or ventilator asynchrony requiring therapeutic intervention during transport. In addition, we assessed the therapeutic benefit of a CT scan control. RESULTS: The final analysis included 31 patients and 31 IHTs. The median duration of IHT was 29 min [25;37]. SIs occurred in 16 patients (52 %) during transport, whereas it was observed in 4 patients (13 %) before (p = 0.002) and 4 patients (13 %) after IHT (p = 0.001). Twenty-four AEs occurred during transport of 19 patients (61 %). One patient benefited from hematoma evacuation after implementation of control CT. CONCLUSION: IHT carries significant SIs and AEs in severe TBI patients. To improve a risk/benefit ratio favorable for patients, a program focusing on IHT complications regarding therapeutic impact of control CT scan is needed.

From the Skin to the Brain: Pathophysiology of Colonization and Infection of External Ventricular Drain, a Prospective Observational Study.

Ventriculostomy-related infection (VRI) is a serious complication of external ventricular drain (EVD) but its natural history is poorly studied. We prospectively tracked the bacteria pathways from skin towards ventricles to identify the infectious process resulting in ventriculostomy-related colonization (VRC), and VRI. We systematically sampled cerebrospinal fluid (CSF) on a daily basis and collected swabs from both the skin and stopcock every 3.0 days for microbiological analysis including in 101 neurosurgical patient. Risk factors for positive event defined as either VRC or VRI were recorded and related to our microbiological findings. A total of 1261 CSF samples, 473 skin swabs, and 450 stopcock swabs were collected. Skin site was more frequently colonized than stopcock (70 (60%) vs 34 (29%), p = 0.023), and earlier (14 ±1.4 vs 24 ±1.5 days, p<0.0001). Sixty-one (52%) and 32 (27%) skin and stopcock sites were colonized with commensal bacteria, 1 (1%) and 1 (1%) with pathogens, 8 (7%) and 1 (1%) with combined pathogens and commensal bacteria, respectively. Sixteen positive events were diagnosed; a cutaneous origin was identified in 69% of cases. The presence of a pathogen at skin site (6/16 vs 4/85, OR: 11.8, [2.5-56.8], p = 0.002) and CSF leakage (7/16 vs 6/85, OR 10 [2.4-41.2], p = 0.001)) were the two independent significant risk factors statistically linked to positive events occurrence. Our results suggest that VRC and VRI mainly results from an extra-luminal progression of pathogens initially colonizing the skin site where CSF leaks.

Isoflurane, 0.5 minimum alveolar concentration administered through the precardiopulmonary bypass period, reduces postoperative dobutamine requirements of cardiac surgery patients: a randomized study.

OBJECTIVE: Cardioprotective properties have been shown with halogenated volatile agents. It was hypothesized that low-dose isoflurane administered before aortic cross-clamping may reduce the amount of dobutamine required to improve impaired postoperative cardiac function after various types of cardiac surgery. DESIGN: A prospective, randomized trial. SETTING: An anesthesia and intensive care unit, university hospital. PARTICIPANTS: Two hundred eighty cardiac surgery patients. INTERVENTIONS: All patients allocated to either isoflurane treatment (T) or no treatment (control group [C]) received total intravenous anesthesia. In the treatment group, isoflurane was administered at a 0.5 minimum alveolar concentration (MAC) from tracheal intubation to initiation of cardiopulmonary bypass (CPB). During weaning from CPB, dobutamine was introduced by using a hemodynamically driven decision tree. MEASUREMENTS AND MAIN RESULTS: The number of patients receiving dobutamine was comparable (66 v 78, p = 0.07, in T and C groups, respectively). The total amount of postoperative dobutamine indexed to patient weight, considered as the primary endpoint, was reduced in the isoflurane-treated group (4.2 +/- 8 v 7.2 +/- 15, p < 0.02, in T and C, respectively). Isoflurane was identified as an independent variable significantly (odds ratio [confidence interval]) influencing the total amount of postoperative dobutamine (0.53 [0.31-0.92], p < 0.02). Postoperative troponin I release at 20 hours was not affected by isoflurane treatment. CONCLUSIONS: This study revealed that exposure to 0.5 MAC isoflurane before CPB reduced the total amount of dobutamine required to normalize postoperative cardiac dysfunction in various types of cardiac surgical patients.

The cytosolic phospholipase A2 pathway, a safeguard of beta2-adrenergic cardiac effects in rat.

We have recently demonstrated that in human heart, beta2-adrenergic receptors (beta2-ARs) are biochemically coupled not only to the classical adenylyl cyclase (AC) pathway but also to the cytosolic phospholipase A2 (cPLA2) pathway (Pavoine, C., Behforouz, N., Gauthier, C., Le Gouvello, S., Roudot-Thoraval, F., Martin, C. R., Pawlak, A., Feral, C., Defer, N., Houel, R., Magne, S., Amadou, A., Loisance, D., Duvaldestin, P., and Pecker, F. (2003) Mol. Pharmacol. 64, 1117-1125). In this study, using Fura-2-loaded cardiomyocytes isolated from adult rats, we showed that stimulation of beta2-ARs triggered an increase in the amplitude of electrically stimulated [Ca2+]i transients and contractions. This effect was abolished with the PKA inhibitor, H89, but greatly enhanced upon addition of the selective cPLA2 inhibitor, AACOCF3. The beta2-AR/cPLA2 inhibitory pathway involved G(i) and MSK1. Potentiation of beta2-AR/AC/PKA-induced Ca2+ responses by AACOCF3 did not rely on the enhancement of AC activity but was associated with eNOS phosphorylation (Ser1177) and L-NAME-sensitive NO production. This was correlated with PKA-dependent phosphorylation of PLB (Ser16). The constraint exerted by the beta2-AR/cPLA2 pathway on the beta2-AR/AC/PKA-induced Ca2+ responses required integrity of caveolar structures and was impaired by Filipin III treatment. Immunoblot analyses demonstrated zinterol-induced translocation of cPLA and its cosedimentation with MSK1, eNOS, PLB, and sarcoplasmic reticulum Ca2+ pump (SERCA) 2a in a low density caveolin-3-enriched membrane fraction. This inferred the gathering of beta2-AR signaling effectors around caveolae/sarcoplasmic reticulum (SR) functional platforms. Taken together, these data highlight cPLA as a cardiac beta2-AR signaling pathway that limits beta2-AR/AC/PKA-induced Ca2+ responses in adult rat cardiomyocytes through the impairment of eNOS activation and PLB phosphorylation.

N-acetylcysteine prevents the deleterious effect of tumor necrosis factor-(alpha) on calcium transients and contraction in adult rat cardiomyocytes.

BACKGROUND: The negative effect of tumor necrosis factor-alpha (TNF-alpha) on heart contraction, which is mediated by sphingosine, is a major component in heart failure. Because the cellular level of glutathione may limit sphingosine production via the inhibition of the Mg-dependent neutral sphingomyelinase (N-SMase), we hypothesized that cardiac glutathione status might determine the negative contractile response to TNF-alpha. METHODS AND RESULTS: We examined the effects of TNF-alpha in isolated cardiomyocytes obtained from control rats or rats that were given the glutathione precursor N-acetylcysteine (NAC, 100 mg IP per animal). In cardiomyocytes obtained from control rats, 25 ng/mL TNF-alpha increased reactive oxygen species generation and N-SMase activity (500% and 34% over basal, respectively) and decreased the amplitude of [Ca(2+)](i) in response to electrical stimulation (22% below basal). NAC treatment increased cardiac glutathione content by 42%. In cardiomyocytes obtained from NAC-treated rats, 25 ng/mL TNF-alpha had no effect on reactive oxygen species production or N-SMase activity but increased the amplitude of [Ca(2+)](i) transients and contraction in response to electrical stimulation by 40% to 50% over basal after 20 minutes. This was associated with a hastened relaxation (20% reduction in t(1/2) compared with basal) and an increased phosphorylation of both Ser(16)- and Thr(17)-phospholamban residues (260% and 115% of maximal isoproterenol effect, respectively). CONCLUSIONS: It is concluded that cardiac glutathione status, by controlling N-SMase activation, determines the severity of the adverse effects of TNF-alpha on heart contraction. Glutathione supplementation may therefore provide therapeutic benefits for vulnerable hearts.