Comparison of the Prognostic Significance of Initial Blood Lactate and Base Deficit in Trauma Patients.

BACKGROUND: Initial blood lactate and base deficit have been shown to be prognostic biomarkers in trauma, but their respective performances have not been compared. METHODS: Blood lactate levels and base deficit were measured at admission in trauma patients in three level 1 trauma centers. This was a retrospective analysis of prospectively acquired data. The association of initial blood lactate and base deficit with mortality was tested using receiver operating characteristics curve, logistic regression using triage scores (Revised Trauma Score and Mechanism Glasgow scale and Arterial Pressure score), and Trauma Related Injury Severity Score as a reference standard. The authors also used a reclassification method. RESULTS: The authors evaluated 1,075 trauma patients (mean age, 39 ± 18 yr, with 90% blunt and 10% penetrating injuries and a mortality of 13%). At admission, blood lactate was elevated in 425 (39%) patients and base deficit was elevated in 725 (67%) patients. Blood lactate was correlated with base deficit (R = 0.54; P < 0.001). Using logistic regression, blood lactate was a better predictor of death than base deficit when considering its additional predictive value to triage scores and Trauma Related Injury Severity Score. This result was confirmed using a reclassification method but only in the subgroup of normotensive patients (n = 745). CONCLUSIONS: Initial blood lactate should be preferred to base deficit as a biologic variable in scoring systems built to assess the initial severity of trauma patients.

Long-term prognosis after out-of-hospital resuscitation of cardiac arrest in trauma patients: prehospital trauma-associated cardiac arrest.

BACKGROUND: Although prehospital cardiac arrest (CA) remains associated with poor long-term outcome, recent studies show an improvement in the survival rate after prehospital trauma associated CA (TCA). However, data on the long-term neurological outcome of TCA, particularly from physician-staffed Emergency Medical Service (EMS), are scarce, and results reported have been inconsistent. The objective of this pilot study was to evaluate the long-term outcome of patients admitted to several trauma centres after a TCA. METHODS: This study is a retrospective database review of all patients from a multicentre prospective registry that experienced a TCA and had undergone successful cardiopulmonary resuscitation (CPR) prior their admission at the trauma centre. The primary end point was neurological outcome at 6 months among patients who survived to hospital discharge. RESULTS: 88 victims of TCA underwent successful CPR and were admitted to the hospital, 90% of whom were victims of blunt trauma. Of these 88 patients, 10 patients (11%; CI 95% 6% to 19%) survived to discharge: on discharge, 9 patients displayed a GCS of 15 and Cerebral Performance Categories (CPC) 1-2 and one patient had a GCS 7 and CPC of 3. Hypoxia was the most frequent cause of CA among survivors. 6-month follow-up was achieved for 9 patients of the 10 surviving patients. The 9 patients with a good outcome on hospital discharge had a CPC of 1 or 2 6 months post discharge. All returned to their premorbid family and social settings. CONCLUSIONS: Among patients admitted to hospital after successful CPR from TCA, hypoxia as the likely aetiology of arrest carried a more favourable prognosis. Most of the patients successfully resuscitated from TCA and surviving to hospital discharge had a good neurological outcome, suggesting that prehospital resuscitation may not be futile.

General anesthetics have differential inhibitory effects on gap junction channels and hemichannels in astrocytes and neurons.

Astrocytes represent a major non-neuronal cell population actively involved in brain functions and pathologies. They express a large amount of gap junction proteins that allow communication between adjacent glial cells and the formation of glial networks. In addition, these membrane proteins can also operate as hemichannels, through which "gliotransmitters" are released, and thus contribute to neuroglial interaction. There are now reports demonstrating that alterations of astroglial gap junction communication and/or hemichannel activity impact neuronal and synaptic activity. Two decades ago we reported that several general anesthetics inhibited gap junctions in primary cultures of astrocytes (Mantz et al., (1993) Anesthesiology 78(5):892-901). As there are increasing studies investigating neuroglial interactions in anesthetized mice, we here updated this previous study by employing acute cortical slices and by characterizing the effects of general anesthetics on both astroglial gap junctions and hemichannels. As hemichannel activity is not detected in cortical astrocytes under basal conditions, we treated acute slices with the endotoxin LPS or proinflammatory cytokines to induce hemichannel activity in astrocytes, which in turn activated neuronal hemichannels. We studied two extensively used anesthetics, propofol and ketamine, and the more recently developed dexmedetomidine. We report that these drugs have differential inhibitory effects on gap junctional communication and hemichannel activity in astrocytes when used in their respective, clinically relevant concentrations, and that dexmedetomidine appears to be the least effective on both channel functions. In addition, the three anesthetics have similar effects on neuronal hemichannels. Altogether, our observations may contribute to optimizing the selection of anesthetics for in vivo animal studies.

G protein-coupled receptor kinase 2 and group I metabotropic glutamate receptors mediate inflammation-induced sensitization to excitotoxic neurodegeneration.

OBJECTIVE: The concept of inflammation-induced sensitization is emerging in the field of perinatal brain injury, stroke, Alzheimer disease, and multiple sclerosis. However, mechanisms underpinning this process remain unidentified. METHODS: We combined in vivo systemic lipopolysaccharide-induced or interleukin (IL)-1ß-induced sensitization of neonatal and adult rodent cortical neurons to excitotoxic neurodegeneration with in vitro IL-1ß sensitization of human and rodent neurons to excitotoxic neurodegeneration. Within these inflammation-induced sensitization models, we assessed metabotropic glutamate receptors (mGluR) signaling and regulation. RESULTS: We demonstrate for the first time that group I mGluRs mediate inflammation-induced sensitization to neuronal excitotoxicity in neonatal and adult neurons across species. Inflammation-induced G protein-coupled receptor kinase 2 (GRK2) downregulation and genetic deletion of GRK2 mimicked the sensitizing effect of inflammation on excitotoxic neurodegeneration. Thus, we identify GRK2 as a potential molecular link between inflammation and mGluR-mediated sensitization. INTERPRETATION: Collectively, our findings indicate that inflammation-induced sensitization is universal across species and ages and that group I mGluRs and GRK2 represent new avenues for neuroprotection in perinatal and adult neurological disorders.

Use of bispectral index to monitor the depth of sedation in mechanically ventilated patients in the prehospital setting.

BACKGROUND: Sedative drug administration is a challenging aspect of the management of mechanically ventilated patients in the out-of-hospital critical care medicine. We hypothesised that the bispectral index of the EEG (BIS) could be a helpful tool in evaluating the depth of sedation in this difficult environment. The main objective of the present study was to assess the agreement of BIS with the clinical scales in the out-of-hospital setting. METHODS: This prospective study included mechanically ventilated patients. BIS values were blindly recorded continuously. A Ramsay score was performed every 5 min. The main judgement criterion was the correlation between BIS values and the Ramsay score. RESULTS: 72 patients were included, mostly presenting with toxic coma (36%) or neurological coma (21%). The median (IQR) BIS value was 85 (84-86) when the Ramsay score was 3, 80 (76-84) when the Ramsay score was 4, 61 (55-80) when the Ramsay score was 5 and 45 (38-60) when the Ramsay score was 6. According to Receiver operating characteristic (ROC) curves, BIS was categorised into three classes (BIS<54 corresponding to Ramsay score 6, 54≤BIS<72 for Ramsay score 5 and BIS≥73 for Ramsay score ≤4). Based on these categories, the proportion of appropriate BIS values was 67% (217/323). The concordance correlation coefficient for repeated measurements was 0.54 (0.43-0.64). The agreement between BIS and the Ramsay score is moderate. CONCLUSIONS: Prehospital measured BIS values appear poorly correlated with clinical assessment of the depth of sedation. For this reason, the use of BIS to guide prehospital sedation cannot be recommended.

Preoperative ketamine administration for prevention of postoperative neurocognitive disorders after major orthopedic surgery in elderly patients: A multicenter randomized blinded placebo-controlled trial.

BACKGROUND: Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition. METHODS: This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery. RESULTS: Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56; 1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95% CI] 0.34 [0.13-0.86]). CONCLUSIONS: A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916).

Effects of a multimodal management strategy for acute mesenteric ischemia on survival and intestinal failure.

BACKGROUND & AIMS: Acute mesenteric ischemia (AMI) is an emergency with a high mortality rate; survivors have high rates of intestinal failure. We performed a prospective study to assess a multidisciplinary and multimodal management approach, focused on intestinal viability. METHODS: In an Intestinal Stroke Center, we developed a multimodal management strategy involving gastroenterologists, vascular and abdominal surgeons, radiologists, and intensive care specialists; it was tested in a pilot study on 18 consecutive patients with occlusive AMI, admitted to a tertiary center from July 2009 to November 2011. Patients with left ischemic colitis, nonocclusive AMI, chronic mesenteric ischemia, and other emergencies were excluded. Patients received specific medical management: revascularization of viable small bowel and/or resection of nonviable small bowel; 12 patients received arterial revascularization. We evaluated the percentages of patients who survived for 30 days or 2 years, the number with permanent intestinal failure, and morbidity. Lengths and rates of intestinal resection were compared with or without revascularization, and in patients with early or late-stage disease. RESULTS: Patients were followed up for a mean of 497 days (range, 7-2085 d); 95% survived for 30 days, 89% survived for 2 years, and 28% had morbidities within 30 days. Intestinal resection was necessary for 7 cases (39%), with mean lengths of intestinal resection of 30 cm and 207 cm, with or without revascularization, respectively (P = .03). Among patients with early or late-stage AMI, rates of resection were 18% and 71%, respectively (P = .049). Patients with early stage disease had shorter lengths of intestinal resection than those with late-stage disease (7 vs 94 cm; P = .02), and spent less time in intensive care (2.5 vs 49.8; P = .02). CONCLUSIONS: A multidisciplinary and multimodal management approach might increase survival of patients with AMI and prevent intestinal failure.

Activation of microglial N-methyl-D-aspartate receptors triggers inflammation and neuronal cell death in the developing and mature brain.

OBJECTIVE: Activated microglia play a central role in the inflammatory and excitotoxic component of various acute and chronic neurological disorders. However, the mechanisms leading to their activation in the latter context are poorly understood, particularly the involvement of N-methyl-D-aspartate receptors (NMDARs), which are critical for excitotoxicity in neurons. We hypothesized that microglia express functional NMDARs and that their activation would trigger neuronal cell death in the brain by modulating inflammation. METHODS AND RESULTS: We demonstrate that microglia express NMDARs in the murine and human central nervous system and that these receptors are functional in vitro. We show that NMDAR stimulation triggers microglia activation in vitro and secretion of factors that induce cell death of cortical neurons. These damaged neurons are further shown to activate microglial NMDARs and trigger a release of neurotoxic factors from microglia in vitro, indicating that microglia can signal back to neurons and possibly induce, aggravate, and/or maintain neurologic disease. Neuronal cell death was significantly reduced through pharmacological inhibition or genetically induced loss of function of the microglial NMDARs. We generated Nr1 LoxP(+/+) LysM Cre(+/-) mice lacking the NMDAR subunit NR1 in cells of the myeloid lineage. In this model, we further demonstrate that a loss of function of the essential NMDAR subunit NR1 protects from excitotoxic neuronal cell death in vivo and from traumatic brain injury. INTERPRETATION: Our findings link inflammation and excitotoxicity in a potential vicious circle and indicate that an activation of the microglial NMDARs plays a pivotal role in neuronal cell death in the perinatal and adult brain.

Neuroprotective effects of dexmedetomidine against glutamate agonist-induced neuronal cell death are related to increased astrocyte brain-derived neurotrophic factor expression.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a prominent role in neuroprotection against perinatal brain injury. Dexmedetomidine, a selective agonist of α2-adrenergic receptors, also provides neuroprotection against glutamate-induced damage. Because adrenergic receptor agonists can modulate BDNF expression, our goal was to examine whether dexmedetomidine's neuroprotective effects are mediated by BDNF modulation in mouse perinatal brain injury. METHODS: The protective effects against glutamate-induced injury of BDNF and dexmedetomidine alone or in combination with either a neutralizing BDNF antibody or an inhibitor of the extracellular signal-regulated kinase pathway (PD098059) were compared in perinatal ibotenate-induced cortical lesions (n = 10-20 pups/groups) and in mouse neuronal cultures (300 µM of ibotenate for 6 h). The effect of dexmedetomidine on BDNF expression was examined in vivo and in vitro with cortical neuronal and astrocyte isolated cultures. RESULTS: Both BDNF and dexmedetomidine produced a significant neuroprotective effect in vivo and in vitro. Dexmedetomidine enhanced Bdnf4 and Bdnf5 transcription and BDNF protein cortical expression in vivo. Dexmedetomidine also enhanced Bdnf4 and Bdnf5 transcription and increased BDNF media concentration in isolated astrocyte cultures but not in neuronal cultures. Dexmedetomidine's protective effect was inhibited with BDNF antibody (mean lesion size ± SD: 577 ± 148 µm vs. 1028 ± 213 µm, n = 14-20, P < 0.001) and PD098059 in vivo but not in isolated neuron cultures. Finally, PD098059 inhibited the increased release of BDNF induced by dexmedetomidine in astrocyte cultures. CONCLUSION: These results suggest that dexmedetomidine increased astrocyte expression of BDNF through an extracellular signal-regulated kinase-dependent pathway, inducing subsequent neuroprotective effects.

Family witnessed resuscitation: nationwide survey of 337 prehospital emergency teams in France.

OBJECTIVE: To assess the practices and opinions of prehospital emergency medical services (EMS) with regard to family witnessed resuscitation (FWR) and to analyse the differences between physicians' and nurses' responses. DESIGN: An anonymous questionnaire (30 yes/no questions on demographics and FWR) was sent to all prehospital emergency staff (physicians, nurses and support staff) working for the 377 Mobile Intensive Care Units in France. RESULTS: Of the 2689 responses received 2664 were analysed. Mean respondent age was 38 ± 8 years, the male to female ratio was 1:2. 87% of respondents had already performed FWR and 38% had offered relatives the option to be present during resuscitation. Most respondents (90%) felt that FWR might cause psychological trauma to the family; 70% thought that FWR might impact on the duration of resuscitation and 68% on EMS team concentration. In the 28% of cases when relatives had asked to be present, 59% of respondents had acquiesced but only 27% were willing to invite relatives to be routinely present. CONCLUSIONS: Prehospital EMS teams in France seems to support FWR but are not yet ready to offer it systematically to relatives. Following our survey, written guidelines are currently in development in our department. These guidelines could be the first step of a national strategy for developing FWR in France. We await results from other studies of family members' opinions to compare prehospital practitioners' and family members' views to further develop our practice.

Misrepresentation of randomized controlled trials in press releases and news coverage: a cohort study.

BACKGROUND: Previous studies indicate that in published reports, trial results can be distorted by the use of "spin" (specific reporting strategies, intentional or unintentional, emphasizing the beneficial effect of the experimental treatment). We aimed to (1) evaluate the presence of "spin" in press releases and associated media coverage; and (2) evaluate whether findings of randomized controlled trials (RCTs) based on press releases and media coverage are misinterpreted. METHODS AND FINDINGS: We systematically searched for all press releases indexed in the EurekAlert! database between December 2009 and March 2010. Of the 498 press releases retrieved and screened, we included press releases for all two-arm, parallel-group RCTs (n = 70). We obtained a copy of the scientific article to which the press release related and we systematically searched for related news items using Lexis Nexis. "Spin," defined as specific reporting strategies (intentional or unintentional) emphasizing the beneficial effect of the experimental treatment, was identified in 28 (40%) scientific article abstract conclusions and in 33 (47%) press releases. From bivariate and multivariable analysis assessing the journal type, funding source, sample size, type of treatment (drug or other), results of the primary outcomes (all nonstatistically significant versus other), author of the press release, and the presence of "spin" in the abstract conclusion, the only factor associated, with "spin" in the press release was "spin" in the article abstract conclusions (relative risk [RR] 5.6, [95% CI 2.8-11.1], p < 0.001). Findings of RCTs based on press releases were overestimated for 19 (27%) reports. News items were identified for 41 RCTs; 21 (51%) were reported with "spin," mainly the same type of "spin" as those identified in the press release and article abstract conclusion. Findings of RCTs based on the news item was overestimated for ten (24%) reports. CONCLUSION: "Spin" was identified in about half of press releases and media coverage. In multivariable analysis, the main factor associated with "spin" in press releases was the presence of "spin" in the article abstract conclusion.

A meta-analysis of the use of nonsteroidal antiinflammatory drugs for pediatric postoperative pain.

BACKGROUND: Opioid side effects are a great concern during the postoperative period in children. Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to effectively decrease postoperative pain, but their opioid-sparing effect is still controversial. In this present meta-analysis, we investigated the postoperative opioid-sparing effect of NSAIDs in children. METHODS: A comprehensive literature search was conducted to identify clinical trials using NSAIDs and opioids as perioperative analgesic compounds in children and infants. Outcomes measured were opioid consumption, pain intensity, postoperative nausea and vomiting (PONV), and urinary retention. All outcomes were studied during postanesthesia care unit (PACU) stay and the first 24 postoperative hours. Data from each trial were combined to calculate the pooled odds ratios (ORs) or standardized mean difference (SMD) and their 95% confidence interval. RESULTS: Twenty-seven randomized controlled studies were analyzed. Perioperative administration of NSAIDs decreased postoperative opioid requirement (both in the PACU and during the first 24 postoperative hours; SMD = -0.66 [-0.84, -0.48] and -0.83 [-1.11, -0.55], respectively), pain intensity in the PACU (SMD = -0.85 [-1.24, -0.47]), and PONV during the first 24 postoperative hours (OR = 0.75 [0.57-0.99]). NSAIDs did not decrease pain intensity during the first 24 postoperative hours (OR = 0.56 [0.26-1.2]) and PONV during PACU stay (OR = 1.02 [0.73-1.44]). Subgroup analysis according to the timing of NSAID administration (intraoperative versus postoperative), type of surgery, or coadministration of paracetamol did not show any influence of these factors on the studied outcomes except the reduction of pain intensity and the incidence of PONV during the first 24 postoperative hours, which were influenced by the coadministration of paracetamol and the type of surgery, respectively. CONCLUSION: This meta-analysis shows that perioperative NSAID administration reduces opioid consumption and PONV during the postoperative period in children.

Predictive factors of PACU stay after herniorraphy in infant: a classification and regression tree analysis.

INTRODUCTION: Herniorraphy is a common surgical intervention in infants, particularly in those born prematurely. Prematurity and perioperative sedation have been shown to be risk factors for postoperative apnea. However, their influence upon PACU stay duration has not been evaluated. The goal of this study was to investigate predictive factors for PACU stay in infants undergoing herniorraphy. MATERIAL AND METHODS: This study is a retrospective analysis of perioperative data in infants <6 months of age undergoing herniorraphy during the period November 2007-November 2009. Collected data included age, gestational age at birth, post-conceptional age, weight, weight at birth, type of anesthesia (spinal vs general), perioperative administration of opioids and paracetamol, duration of surgery, duration of PACU stay, and apnea in PACU. Data analysis used classification and regression trees (CART) with a 10-fold cross-validation. RESULTS: Two hundred and ninety-six patients were included in the analysis. Five parameters were found to predict the duration of PACU stay: a post-conceptional age below 45 weeks, prematurity, general anesthesia, postoperative opioid administration, and the use of intraoperative regional analgesia. CRT method allows constructing a decision tree with eight terminal nodes. The percentage of explained variability of the model and the cross-validation were 79.7% and 76.6%, respectively. DISCUSSION: Our study allows construction of an accurate predictive tree for PACU stay during herniorraphy in infants <6 months. Parameters found to influence the duration of PACU stay were related to anesthesia techniques and perinatal outcomes.

An evaluation of the role of gene expression in the prediction and diagnosis of ventilator-associated pneumonia.

BACKGROUND: The SepsiChip project explored transcriptional modulation associated with ventilator-associated pneumonia (VAP) in patients admitted to the intensive care unit for trauma. Genome-wide expression analysis may help to identify potential diagnostic markers for diseases. The current study examined the changes in blood transcriptome during VAP. METHODS: The authors prospectively included 165 trauma patients, and 41 developed VAP. Whole blood samples were collected at admission and at VAP. To predict VAP, the admission samples were compared by microarray in patients who did or did not develop VAP. To identify diagnosis markers, paired samples of 35 patients who developed VAP were analyzed. Using NanoString (Seattle, WA), the results were confirmed in the patients who developed VAP. Trauma patients who did not develop VAP served as controls to eliminate a time effect. RESULTS: The injury severity scores of the patients who did or did not develop VAP were 36 and 29, respectively. No predictive biomarker was identified. For patients who developed VAP, a transcriptional signature was identified between the two sampling times. However, this signature was a generalized pattern related to trauma, independent of the infectious process. Genes involved in the proinflammatory response were down-regulated in the patients who developed VAP, but this difference was not statistically significant. CONCLUSIONS: In contrast to clinical assessment, transcriptional analysis of whole blood samples cannot predict or diagnose VAP in trauma patients. Differentiating infection from inflammation seems challenging.

Ketamine for perioperative pain management in children: a meta-analysis of published studies.

INTRODUCTION: Balanced analgesia, using both opioid and nonopioids agents, has become the standard care for postoperative pain management. Ketamine, a compound with analgesic and antihyperalgesic properties, has been shown to decrease postoperative pain and opioid requirements in adults. The goal of the present meta-analysis was to investigate postoperative analgesic properties of ketamine in pediatric patients. MATERIAL AND METHODS: A comprehensive literature search was conducted to identify clinical trials that used ketamine as a perioperative analgesic compound in children and infants. Outcomes measured were postoperative analgesic consumption, pain intensity and duration of sensory block (when ketamine was used by caudal route) during the postoperative care unit (PACU) stay and the early postoperative period (6-24 h after leaving the operative room). The data from each trial were combined to calculate the pooled odds ratios or standard mean differences and their 95% confidence intervals. RESULTS: Thirty-five randomized, blinded controlled studies were retrieved from the literature. Systemic ketamine was effective in decreasing PACU pain intensity and analgesic requirement but failed to influence early (6-24 h) pain intensity and analgesic requirement. Ketamine administered locally during tonsillectomy, decreased PACU and early (6-24 h) pain intensity and PACU analgesic requirements. Used as an adjuvant for caudal analgesia, ketamine increased the duration of sensory block and PACU analgesic requirement without impacting PACU pain intensity. Ketamine failed to exhibit a postoperative opioid-sparing effect. CONCLUSIONS: This meta-analysis found that administration of ketamine was associated with decreased PACU postoperative pain intensity and nonopioid analgesic requirement. However, ketamine failed to exhibit a postoperative opioid-sparing effect.

Dexmedetomidine: new insights.

Dexmedetomidine is a potent alpha-2-adrenergic agonist, more selective than clonidine, with widespread actions on the mammalian brain that include sedation, anaesthetic-sparing, analgesia and sympatholytic properties. A large body of recent work supports its favourable profile in improving outcome and long-term brain function in the critically ill. The source of these benefits may lie in the neuroprotective properties that are seen in experimental models and in the clinical setting, in which it can attenuate delirium, preserve sleep architecture, preserve ventilatory drive and decrease sympathetic tone and inflammatory response. Dexmedetomidine may also be a valuable adjuvant when regional anaesthesia is used. Future research should aim at establishing the risk/benefit ratio when used at the bedside.

Early-onset pneumonia after liver transplantation: microbiological findings and therapeutic consequences.

Early-onset hospital-acquired pneumonia (E-HAP) is one of the leading causes of sepsis and mortality after liver transplantation (LT). The appropriate antimicrobial therapy is crucially important for surviving sepsis in this context. The aim of this study was to analyze microbiological findings, associated factors, and optimal antibiotic regimens for E-HAP after LT. Patients demonstrating E-HAP in a single-center cohort of 148 LT recipients were prospectively detected. The diagnosis of pneumonia relied on a combination of supportive clinical findings and a positive culture of a lower respiratory tract sample. E-HAP was considered present if pneumonia occurred within 6 days of intensive care unit (ICU) admission after LT. Twenty-three patients (15.5%) developed E-HAP, which were caused by 36 pathogens (61.1% were gram-negative bacilli, and 33.3% were classified as hospital-acquired). For patients who developed E-HAP, the duration of mechanical ventilation and the ICU stay were significantly longer. Despite a trend toward higher mortality at any time in the E-HAP group, there was no significant difference in mortality between patients with E-HAP and patients without E-HAP. Lactatemia, vasopressor requirements, Simplified Acute Physiology Score II (SAPS II) score on ICU admission, and mechanical ventilation lasting more than 48 hours after LT were associated with E-HAP. Combinations of broad-spectrum ß-lactams and aminoglycosides were active against more than 91% of the encountered pathogens. However, antibiotic de-escalation was possible in more than one-third of cases after identification of the pathogens. In conclusion, E-HAP after LT is a severe condition that appears to be influenced by physiological derangements induced by the surgery, such as lactatemia, vasopressor requirements, and mechanical ventilation requirements, as well as the postoperative SAPS II score. At the time of treatment initiation, an antimicrobial regimen usually proposed for late-onset pneumonia should be followed.

Urological surgery and antiplatelet drugs after cardiac and cerebrovascular accidents.

PURPOSE: The perioperative treatment of patients on dual antiplatelet therapy after myocardial infarction, cerebrovascular event or coronary stent implantation represents an increasingly frequent issue for urologists and anesthesiologists. We assess the current scientific evidence and propose strategies concerning treatment of these patients. MATERIALS AND METHODS: A MEDLINE and PubMed search was conducted for articles related to antiplatelet therapy after myocardial infarction, coronary stents and cerebrovascular events, as well as the use of aspirin and/or clopidogrel in the context of surgery. RESULTS: Early discontinuation of antiplatelet therapy for secondary prevention is associated with a high risk of coronary thrombosis, which is further increased by the hypercoagulable state induced by surgery. Aspirin has recently been recommended as a lifelong therapy. Clopidogrel is mandatory for 6 weeks after myocardial infarction and bare metal stents, and for 12 months after drug-eluting stents. Surgery must be postponed beyond these waiting periods or performed with patients receiving dual antiplatelet therapy because withdrawal therapy increases 5 to 10 times the risk of postoperative myocardial infarction, stent thrombosis or death. The shorter the waiting period between revascularization and surgery the greater the risk of adverse cardiac events. The risk of surgical hemorrhage is increased approximately 20% by aspirin and 50% by clopidogrel. CONCLUSIONS: The risk of coronary thrombosis when antiplatelet agents are withdrawn before surgery is generally higher than the risk of surgical hemorrhage when antiplatelet agents are maintained. However, this issue has not yet been sufficiently evaluated in urological patients and in many instances during urological surgery the risk of bleeding can be dangerous. A thorough dialogue among surgeon, cardiologist and anesthesiologist is essential to determine all risk factors and define the best possible strategy for each patient.

Characterization of the postconditioning effect of dexmedetomidine in mouse organotypic hippocampal slice cultures exposed to oxygen and glucose deprivation.

BACKGROUND: There is an increasing interest in the use of dexmedetomidine for anesthesia and sedation. Here, we used the mouse organotypic hippocampal slice culture to investigate whether dexmedetomidine exhibits postconditioning properties against oxygen and glucose deprivation (OGD). The role of the focal adhesion and extracellular-regulated kinases pathways in these effects were examined in both postconditioning and preconditioning. MATERIALS AND METHODS: Slices were obtained from P5 mouse. In postconditioning experiments, Dexmedetomidine (1 microm) was incubated 60 min after the end of OGD. In preconditioning experiments, dexmedetomidine was applied 3 h before OGD. Pharmacologic modulation of the studied pathways was achieved by using selective inhibitors of these cascades. Cell death was assessed 72 h after OGD using propidium iodide labeling and protein expression of activated caspase 3. RESULTS: Maximum cell death increased with the duration of OGD. Dexmedetomidine induced a postconditioning effect in the CA1 (but not dentate gyrus) subfield area, which was significantly reduced by modulators of the focal adhesion and the extracellular-regulated kinases pathways. The combination of the inhibitors of the two pathways completely abolished the postconditioning effect of dexmedetomidine. The preconditioning effect of dexmedetomidine against ischemia-induced injury was observed in all hippocampal subfield areas. Results obtained with the pharmacologic modulation used for postconditioning also applied to dexmedetomidine-induced preconditioning. DISCUSSION: Dexmedetomidine exhibits significant, but moderate, postconditioning properties against oxygen and glucose deprivation-induced injury. Activation of focal adhesion and the imidazoline 1 receptors-extracellular-regulated kinases pathways is involved in dexmedetomidine-induced postconditioning and preconditioning as well.