Complications of different ventilation strategies in endoscopic laryngeal surgery: a 10-year review.

BACKGROUND: Spontaneous ventilation, mechanical controlled ventilation, apneic intermittent ventilation, and jet ventilation are commonly used during interventional suspension microlaryngoscopy. The aim of this study was to investigate specific complications of each technique, with special emphasis on transtracheal and transglottal jet ventilation. METHODS: The authors performed a retrospective single-institution analysis of a case series of 1,093 microlaryngoscopies performed in 661 patients between January 1994 and January 2004. Data were collected from two separate prospective databases. Feasibility and complications encountered with each technique of ventilation were analyzed as main outcome measures. RESULTS: During 1,093 suspension microlaryngoscopies, ventilation was supplied by mechanical controlled ventilation via small endotracheal tubes (n = 200), intermittent apneic ventilation (n = 159), transtracheal jet ventilation (n = 265), or transglottal jet ventilation (n = 469). Twenty-nine minor and 4 major complications occurred. Seventy-five percent of the patients with major events had an American Society of Anesthesiologists physical status classification of III. Five laryngospasms were observed with apneic intermittent ventilation. All other 24 complications (including 7 barotrauma) occurred during jet ventilation. Transtracheal jet ventilation was associated with a significantly higher complication rate than transglottal jet ventilation (P < 0.0001; odds ratio, 4.3 [95% confidence interval, 1.9-10.0]). All severe complications were related to barotraumas resulting from airway outflow obstruction during jet ventilation, most often laryngospasms. CONCLUSIONS: The use of a transtracheal cannula was the major independent risk factor for complications during jet ventilation for interventional microlaryngoscopy. The anesthetist's vigilance in clinically detecting and preventing outflow airway obstruction remains the best prevention of barotrauma during subglottic jet ventilation.

Is PaCO2 management optimal under controlled mechanical ventilation (CMV) during neuro-resuscitation?

INTRODUCTION. Both hypocapnia and hypercapnia can be deleterious to brain injured patients. Strict PaCO2 control is difficult to achieve because of patient's instability and unpredictable effects of ventilator settings changes. OBJECTIVE. The aim of this study was to evaluate our ability to comply with a protocol of controlled mechanical ventilation (CMV) aiming at a PaCO2 between 35 and 40 mmHg in patients requiring neuro-resuscitation. METHODS. Retrospective analysis of consecutive patients (2005-2011) requiring intracranial pressure (ICP) monitoring for traumatic brain injury (TBI), subarachnoid haemorrhage (SAH), intracranial haemorrhage (ICH) or ischemic stroke (IS). Demographic data, GCS, SAPS II, hospital mortality, PaCO2 and ICP values were recorded. During CMV in the first 48 h after admission, we analyzed the time spent within the PaCO2 target in relation to the presence or absence of intracranial hypertension (ICP[20 mmHg, by periods of 30 min) (Table 1). We also compared the fraction of time (determined by linear interpolation) spent with normal, low or high PaCO2 in hospital survivors and non-survivors (Wilcoxon, Bonferroni correction, p\0.05) (Table 2). PaCO2 samples collected during and after apnoea tests were excluded. Results given as median [IQR]. RESULTS. 436 patients were included (TBI: 51.2 %, SAH: 20.6 %, ICH: 23.2 %, IS: 5.0 %), age: 54 [39-64], SAPS II score: 52 [41-62], GCS: 5 [3-8]. 8744 PaCO2 samples were collected during 150611 h of CMV. CONCLUSIONS. Despite a high number of PaCO2 samples collected (in average one sample every 107 min), our results show that patients undergoing CMV for neuro- resuscitation spent less than half of the time within the pre-defined PaCO2 range. During documented intracranial hypertension, hypercapnia was observed in 17.4 % of the time. Since non-survivors spent more time with hypocapnia, further analysis is required to determine whether hypocapnia was detrimental per se, or merely reflects increased severity of brain insult.

Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation.

OBJECTIVE: Before a patient can be connected to a mechanical ventilator, the controls of the apparatus need to be set up appropriately. Today, this is done by the intensive care professional. With the advent of closed loop controlled mechanical ventilation, methods will be needed to select appropriate start up settings automatically. The objective of our study was to test such a computerized method which could eventually be used as a start-up procedure (first 5-10 minutes of ventilation) for closed-loop controlled ventilation. DESIGN: Prospective Study. SETTINGS: ICU's in two adult and one children's hospital. PATIENTS: 25 critically ill adult patients (age > or = 15 y) and 17 critically ill children selected at random were studied. INTERVENTIONS: To stimulate 'initial connection', the patients were disconnected from their ventilator and transiently connected to a modified Hamilton AMADEUS ventilator for maximally one minute. During that time they were ventilated with a fixed and standardized breath pattern (Test Breaths) based on pressure controlled synchronized intermittent mandatory ventilation (PCSIMV). MEASUREMENTS AND MAIN RESULTS: Measurements of airway flow, airway pressure and instantaneous CO2 concentration using a mainstream CO2 analyzer were made at the mouth during application of the Test-Breaths. Test-Breaths were analyzed in terms of tidal volume, expiratory time constant and series dead space. Using this data an initial ventilation pattern consisting of respiratory frequency and tidal volume was calculated. This ventilation pattern was compared to the one measured prior to the onset of the study using a two-tailed paired t-test. Additionally, it was compared to a conventional method for setting up ventilators. The computer-proposed ventilation pattern did not differ significantly from the actual pattern (p > 0.05), while the conventional method did. However the scatter was large and in 6 cases deviations in the minute ventilation of more than 50% were observed. CONCLUSIONS: The analysis of standardized Test Breaths allows automatic determination of an initial ventilation pattern for intubated ICU patients. While this pattern does not seem to be superior to the one chosen by the conventional method, it is derived fully automatically and without need for manual patient data entry such as weight or height. This makes the method potentially useful as a start up procedure for closed-loop controlled ventilation.

Neurally Adjusted Ventilatory Assist (NAVA) improves the matching of diaphragmatic electrical activity and tidal volume in comparison to pressure support (PS) under non invasive ventilation

INTRODUCTION. Patient-ventilator asynchrony is a frequent issue in non invasivemechanical ventilation (NIV) and leaks at the patient-mask interface play a major role in itspathogenesis. NIV algorithms alleviate the deleterious impact of leaks and improve patient-ventilator interaction. Neurally adusted ventilatory assist (NAVA), a neurally triggered modethat avoids interferences between leaks and the usual pneumatic trigger, could further improvepatient-ventilator interaction in NIV patients.OBJECTIVES. To evaluate the feasibility ofNAVAin patients receiving a prophylactic postextubationNIV and to compare the respective impact ofPSVandNAVAwith and withoutNIValgorithm on patient-ventilator interaction.METHODS. Prospective study conducted in 16 beds adult critical care unit (ICU) in a tertiaryuniversity hospital. Over a 2 months period, were included 17 adult medical ICU patientsextubated for less than 2 h and in whom a prophylactic post-extubation NIV was indicated.Patients were randomly mechanically ventilated for 10 min with: PSV without NIV algorithm(PSV-NIV-), PSV with NIV algorithm (PSV-NIV+),NAVAwithout NIV algorithm (NAVANIV-)and NAVA with NIV algorithm (NAVA-NIV+). Breathing pattern descriptors, diaphragmelectrical activity, leaks volume, inspiratory trigger delay (Tdinsp), inspiratory time inexcess (Tiexcess) and the five main asynchronies were quantified. Asynchrony index (AI) andasynchrony index influenced by leaks (AIleaks) were computed.RESULTS. Peak inspiratory pressure and diaphragm electrical activity were similar in thefour conditions. With both PSV and NAVA, NIV algorithm significantly reduced the level ofleak (p\0.01). Tdinsp was not affected by NIV algorithm but was shorter in NAVA than inPSV (p\0.01). Tiexcess was shorter in NAVA and PSV-NIV+ than in PSV-NIV- (p\0.05).The prevalence of double triggering was significantly lower in PSV-NIV+ than in NAVANIV+.As compared to PSV,NAVAsignificantly reduced the prevalence of premature cyclingand late cycling while NIV algorithm did not influenced premature cycling. AI was not affectedby NIV algorithm but was significantly lower in NAVA than in PSV (p\0.05). AIleaks wasquasi null with NAVA and significantly lower than in PSV (p\0.05).CONCLUSIONS. NAVA is feasible in patients receiving a post-extubation prophylacticNIV. NAVA and NIV improve patient-ventilator synchrony in different manners. NAVANIV+offers the best patient-ventilator interaction. Clinical studies are required to assess thepotential clinical benefit of NAVA in patients receiving NIV.

Respiratory variability in mechanically ventilated patients. Critical Care 2011

Introduction: Increased respiratory pattern variability is associated with improved oxygenation. Pressure support (PS) is a widely used partial-assist mechanical ventilation (MV) mode, in which each breathing cycle is initiated by flow or pressure variation at the airway due to patient inspiratory effort. Neurally adjusted ventilatory assist (NAVA) is relatively new and uses the electrical activity of the diaphragm (Eadi) to deliver ventilatory support proportional to the patient's inspiratory demand. We hypothesize that respiratory variability should be greater with NAVA compared with PS.Methods: Twenty-two patients underwent 20 minutes of PS followed by 20 minutes of NAVA. Flow and Eadi curves were used to obtain tidal volume (Vt) and ∫Eadi for 300 to 400 breaths in each patient. Patient-specific cumulative distribution functions (CDF) show the percentage Vt and ∫Eadi within a clinically defined (±10%) variability band for each patient. Values are normalized to patient-specific medians for direct comparison. Variability in Vt (outcome) is thus expressed in terms of variability in ∫Eadi (demand) on the same plot.Results: Variability in Vt relative to variability in ∫Eadi is significantly greater for NAVA than PS (P = 0.00012). Hence, greater variability in outcome Vt is obtained for a given demand in ∫Eadi, under NAVA, as illustrated in Figure 1 for a typical patient. A Fisher 2 × 2 contingency analysis showed that 45% of patients under NAVA had a Vt variability in equal proportion to ∫Eadi variability, versus 0% for PS (P < 0.05).Conclusions: NAVA yields greater variability in tidal volume, relative to ∫Eadi demand, and a better match between Vt and ∫Eadi. These results indicate that NAVA could achieve improved oxygenation compared with PS when sufficient underlying variability in ∫Eadi is present, due to its ability to achieve higher tidal volume variability from a given variability in ∫Eadi.

Impact of bedside open lung biopsies on the management of mechanically ventilated immunocompromised patients with acute respiratory distress syndrome of unknown etiology.

BACKGROUND: Open lung biopsy (OLB) is helpful in the management of patients with acute respiratory distress syndrome (ARDS) of unknown etiology. We determine the impact of surgical lung biopsies performed at the bedside on the management of patients with ARDS. METHODS: We reviewed all consecutive cases of patients with ARDS who underwent a surgical OLB at the bedside in a medical intensive care unit between 1993 and 2005. RESULTS: Biopsies were performed in 19 patients mechanically ventilated for ARDS of unknown etiology despite extensive diagnostic process and empirical therapeutic trials. Among them, 17 (89%) were immunocompromised and 10 patients experienced hematological malignancies. Surgical biopsies were obtained after a median (25%-75%) mechanical ventilation of 5 (2-11) days; mean (+/-SD) Pao(2)/Fio(2) ratio was 119.3 (+/-34.2) mm Hg. Histologic diagnoses were obtained in all cases and were specific in 13 patients (68%), including 9 (47%) not previously suspected. Immediate complications (26%) were local (pneumothorax, minimal bleeding) without general or respiratory consequences. The biopsy resulted in major changes in management in 17 patients (89%). It contributed to a decision to limit care in 12 of 17 patients who died. CONCLUSION: Our data confirm that surgical OLB may have an important impact on the management of patients with ARDS of unknown etiology after extensive diagnostic process. The procedure can be performed at the bedside, is safe, and has a high diagnostic yield leading to major changes in management, including withdrawal of vital support, in the majority of patients.

A randomized, double blind, placebo-controlled trial of pioglitazone in combination with riluzole in amyotrophic lateral sclerosis.

BACKGROUND: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). METHODS/PRINCIPAL FINDINGS: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole. TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118.

Safety of combined heat and moisture exchanger filters in long-term mechanical ventilation.

STUDY OBJECTIVE: To evaluate the safety of a combined heat and moisture exchanger filter (HMEF) for the conditioning of inspired gas in long-term mechanical ventilation (MV). DESIGN: Randomized controlled trial. SETTING: Medical ICU in a large teaching hospital. PATIENTS: One hundred fifteen consecutive patients who required > or = 48 h of MV. INTERVENTIONS: Patients were randomized at intubation time (day 1) to receive inspired gas conditioned either by a water-bath humidifier heated at 32 degrees C (HWBH) or by an HMEF (Hygroster; DAR; Mirandola, Italy). MEASUREMENTS AND MAIN RESULTS: The two study groups were comparable in terms of primary pathologic condition at the time of hospital admission, disease severity as measured by the Simplified Acute Physiology Score, and ICU mortality. They did not differ with respect to ventilator days per patient (mean +/- SD: HMEF, 7.6 +/- 6.5; HWBH, 7.8 +/- 5.8), incidence of endotracheal tube obstruction (HMEF, 0/59; HWBH, 1/56), and incidence of hypothermic episodes (HMEF, five; HWBH, two). In 41 patients receiving MV for > or = 5 days, the morphologic integrity of respiratory epithelium was evaluated on day 1 and day 5, using a cytologic examination of tracheal aspirate smears. The state of ciliated epithelium was scored on a scale from 0 (poorest integrity) to 1,200 (maximum integrity), according to a well-described method. In both patient groups, the scores slightly but significantly decreased from day 1 to day 5 (mean +/- SD: HWBH, from 787 +/- 104 to 745 +/- 88; HMEF, from 813 +/- 79 to 739 +/- 62; p < 0.01 for both groups); there were no statistically significant differences between groups. CONCLUSIONS: These data indicate acceptable safety of HMEFs of the type used in the present study for long-term mechanical ventilation.

A highly sensitive LC-tandem MS assay for the measurement in plasma and in urine of salbutamol administered by nebulization during mechanical ventilation in healthy volunteers.

The new-generation nebulizers are commonly used for the administration of salbutamol in mechanically ventilated patients. The different modes of administration and new devices have not been compared. We developed a liquid chromatography-tandem mass spectrometry method for the determination of concentrations as low as 0.05 ng/mL of salbutamol, corresponding to the desired plasma concentration after inhalation. Salbutamol quantification was performed by reverse-phase HPLC. Analyte quantification was performed by electrospray ionization-triple quadrupole mass spectrometry using selected reaction monitoring detection ESI in the positive mode. The method was validated over concentrations ranging from 0.05 to 100 ng/mL in plasma and from 0.18 to 135 ng/mL in urine. The method is precise, with mean inter-day coefficient of variation (CV%) within 3.1-8.3% in plasma and 1.3-3.9% in urine, as well as accurate. The proposed method was found to reach the required sensitivity for the evaluation of different nebulizers as well as nebulization modes. The present assay was applied to examine whether salbutamol urine levels, normalized with the creatinine levels, correlated with the plasma concentrations. A suitable, convenient and noninvasive method of monitoring patients receiving salbutamol by mechanical ventilation could be implemented. Copyright © 2011 John Wiley & Sons, Ltd.

A prospective, randomized, and controlled study of fluid management in children with severe head injury: lactated Ringer's solution versus hypertonic saline.

OBJECTIVES: Resuscitation in severe head injury may be detrimental when given with hypotonic fluids. We evaluated the effects of lactated Ringer's solution (sodium 131 mmol/L, 277 mOsm/L) compared with hypertonic saline (sodium 268 mmol/L, 598 mOsm/L) in severely head-injured children over the first 3 days after injury. DESIGN: An open, randomized, and prospective study. SETTING: A 16-bed pediatric intensive care unit (ICU) (level III) at a university children's hospital. PATIENTS: A total of 35 consecutive children with head injury. INTERVENTIONS: Thirty-two children with Glasgow Coma Scores of <8 were randomly assigned to receive either lactated Ringer's solution (group 1) or hypertonic saline (group 2). Routine care was standardized, and included the following: head positioning at 30 degrees; normothermia (96.8 degrees to 98.6 degrees F [36 degrees to 37 degrees C]); analgesia and sedation with morphine (10 to 30 microg/kg/hr), midazolam (0.2 to 0.3 mg/kg/hr), and phenobarbital; volume-controlled ventilation (PaCO2 of 26.3 to 30 torr [3.5 to 4 kPa]); and optimal oxygenation (PaO2 of 90 to 105 torr [12 to 14 kPa], oxygen saturation of >92%, and hematocrit of >0.30). MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure and intracranial pressure (ICP) were monitored continuously and documented hourly and at every intervention. The means of every 4-hr period were calculated and serum sodium concentrations were measured at the same time. An ICP of 15 mm Hg was treated with a predefined sequence of interventions, and complications were documented. There was no difference with respect to age, male/female ratio, or initial Glasgow Coma Score. In both groups, there was an inverse correlation between serum sodium concentration and ICP (group 1: r = -.13, r2 = .02, p < .03; group 2: r = -.29, r2 = .08, p < .001) that disappeared in group 1 and increased in group 2 (group 1: r = -.08, r2 = .01, NS; group 2: r = -.35, r2 =.12, p < .001). Correlation between serum sodium concentration and cerebral perfusion pressure (CPP) became significant in group 2 after 8 hrs of treatment (r = .2, r2 = .04, p = .002). Over time, ICP and CPP did not significantly differ between the groups. However, to keep ICP at <15 mm Hg, group 2 patients required significantly fewer interventions (p < .02). Group 1 patients received less sodium (8.0 +/- 4.5 vs. 11.5 +/- 5.0 mmol/kg/day, p = .05) and more fluid on day 1 (2850 +/- 1480 vs. 2180 +/- 770 mL/m2, p = .05). They also had a higher frequency of acute respiratory distress syndrome (four vs. 0 patients, p = .1) and more than two complications (six vs. 1 patient, p = .09). Group 2 patients had significantly shorter ICU stay times (11.6 +/- 6.1 vs. 8.0 +/- 2.4 days; p = .04) and shorter mechanical ventilation times (9.5 +/- 6.0 vs. 6.9 +/- 2.2 days; p = .1). The survival rate and duration of hospital stay were similar in both groups. CONCLUSIONS: Treatment of severe head injury with hypertonic saline is superior to that treatment with lactated Ringer's solution. An increase in serum sodium concentrations significantly correlates with lower ICP and higher CPP. Children treated with hypertonic saline require fewer interventions, have fewer complications, and stay a shorter time in the ICU.

Novel micropatterns mechanically control fibrotic reactions at the surface of silicone implants.

Over the past decade, various implantable devices have been developed to treat diseases that were previously difficult to manage such diabetes, chronic pain, and neurodegenerative disorders. However, translation of these novel technologies into clinical practice is often difficult because fibrotic encapsulation and/or rejection impairs device function after body implantation. Ideally, cells of the host tissue should perceive the surface of the implant being similar to the normal extracellular matrix. Here, we developed an innovative approach to provide implant surfaces with adhesive protein micropatterns. The patterns were designed to promote adhesion of fibroblasts and macrophages by simultaneously suppressing fibrogenic activation of both cell types. In a rat model, subcutaneously implanted silicone pads provided with the novel micropatterns caused 6-fold lower formation of inflammatory giant cells compared with clinical grade, uncoated, or collagen-coated silicone implants. We further show that micropatterning of implants resulted in 2-3-fold reduced numbers of pro-fibrotic myofibroblast by inhibiting their mechanical activation. Our novel approach allows controlled cell attachment to implant surfaces, representing a critical advance for enhanced biointegration of implantable medical devices.

CLOCK-controlled polyphonic regulation of circadian rhythms through canonical and noncanonical E-boxes.

In mammalian circadian clockwork, the CLOCK-BMAL1 complex binds to DNA enhancers of target genes and drives circadian oscillation of transcription. Here we identified 7,978 CLOCK-binding sites in mouse liver by chromatin immunoprecipitation-sequencing (ChIP-Seq), and a newly developed bioinformatics method, motif centrality analysis of ChIP-Seq (MOCCS), revealed a genome-wide distribution of previously unappreciated noncanonical E-boxes targeted by CLOCK. In vitro promoter assays showed that CACGNG, CACGTT, and CATG(T/C)G are functional CLOCK-binding motifs. Furthermore, we extensively revealed rhythmically expressed genes by poly(A)-tailed RNA-Seq and identified 1,629 CLOCK target genes within 11,926 genes expressed in the liver. Our analysis also revealed rhythmically expressed genes that have no apparent CLOCK-binding site, indicating the importance of indirect transcriptional and posttranscriptional regulations. Indirect transcriptional regulation is represented by rhythmic expression of CLOCK-regulated transcription factors, such as Krüppel-like factors (KLFs). Indirect posttranscriptional regulation involves rhythmic microRNAs that were identified by small-RNA-Seq. Collectively, CLOCK-dependent direct transactivation through multiple E-boxes and indirect regulations polyphonically orchestrate dynamic circadian outputs.

Effects of motive-oriented therapeutic relationship in a ten-session general psychiatric treatment of borderline personality disorder: a randomized controlled trial.

Background: Motive-oriented therapeutic relationship (MOTR) was postulated to be a particularly helpful therapeutic ingredient in the early treatment phase of patients with personality disorders, in particular with borderline personality disorder (BPD). The present randomized controlled study using an add-on design is the first study to test this assumption in a 10-session general psychiatric treatment with patients presenting with BPD on symptom reduction and therapeutic alliance. Methods: A total of 85 patients were randomized. They were either allocated to a manual-based short variant of the general psychiatric management (GPM) treatment (in 10 sessions) or to the same treatment where MOTR was deliberately added to the treatment. Treatment attrition and integrity analyses yielded satisfactory results. Results: The results of the intent-to-treat analyses suggested a global efficacy of MOTR, in the sense of an additional reduction of general problems, i.e. symptoms, interpersonal and social problems (F1, 73 = 7.25, p < 0.05). However, they also showed that MOTR did not yield an additional reduction of specific borderline symptoms. It was also shown that a stronger therapeutic alliance, as assessed by the therapist, developed in MOTR treatments compared to GPM (Z55 = 0.99, p < 0.04). Conclusions: These results suggest that adding MOTR to psychiatric and psychotherapeutic treatments of BPD is promising. Moreover, the findings shed additional light on the perspective of shortening treatments for patients presenting with BPD. © 2014 S. Karger AG, Basel.

The tectonically controlled emplacement of a vertically sheeted gabbro-pyroxenite intrusion: Feeder-zone of an ocean-island volcano (Fuerteventura, Canary Islands)

The Miocene PX1 gabbro-pyroxenite pluton, Fuerteventura, Canary Islands, is a 3.5 x 5.5 km shallow-level intrusion (0.15-0.2 GPa and 1100-1120 degrees C), interpreted as the feeder-zone to an ocean-island volcano. It displays a vertical magmatic banding expressed in five 50 to 100 metre-wide NNE-SSW trending alkaline gabbro sequences alternating with pyroxenites. This emplacement geometry was controlled by brittle to ductile shear zones, generated by a regional E-W extensional tectonic setting that affected Fuerteventura during the Miocene. At a smaller scale, the PX1 gabbro and pyroxenite bands consist of metre-thick differentiation units, which suggest emplacement by periodic injection of magma pulses as vertical dykes that amalgamated, similarly to a sub-volcanic sheeted dyke complex. Individual dykes underwent internal differentiation following a solidification front parallel to the dyke edges. This solidification front may have been favoured by a significant lateral/horizontal thermal gradient, expressed by the vertical banding in the gabbros, the fractionation asymmetry within individual dykes and the migmatisation of the wall rocks. Pyroxenitic layers result from the fractionation and accumulation of clinopyroxene +/- olivine +/- plagioclase crystals from a mildly alkaline basaltic liquid. They are interpreted as truncated differentiation sequences, from which residual melts were extracted at various stages of their chemical evolution by subsequent dyke intrusions, either next to or within the crystallising unit. Compaction and squeezing of the crystal mush is ascribed to the incoming and inflating magma pulses. The expelled interstitial liquid was likely collected and erupted along with the magma flowing through the newly injected dykes. Clinopyroxene mineral orientation - as evidenced by EBSD and micro X-ray tomography investigations - displays a marked pure-shear component, supporting the interpretation of the role of compaction in the generation of the pyroxenites. Conversely, gabbro sequences underwent minor melt extraction and are believed to represent crystallised coalesced magma batches emplaced at lower rates at the end of eruptive cycles. Clinopyroxene orientations in gabbros record a simple shear component suggesting syn-magmatic deformation parallel to observed NNE-SSW trending shear zones induced by the regional tensional stress field. This emplacement model implies a crystallisation time of 1 to 5 years for individual dykes, consistent with PX1 emplacement over less than 0.5 My. A minimum amount of approximately 150 km(3) of magma is needed to generate the pluton, part of it having been erupted through the Central Volcanic Centre of Fuerteventura. If the regional extensional tectonic regime controls the PX1 feeder-zone initiation and overall geometry, rates and volumes of magma depend on other, source-related factors. High injection rates are likely to induce intrusion growth rates larger than could be accommodated by the regional extension. In this case, dyke intrusion by propagation of a weak tip, combined with the inability of magma to circulate through previously emplaced and crystallised dykes could result in an increase of non-lithostatic pressure on previously emplaced mushy dyke walls; thus generating strong pure-shear compaction within the pluton feeder-zone and interstitial melt expulsion. These compaction-dominated processes are recorded by the cumulitic pyroxenite bands. (C) 2010 Elsevier B.V. All rights reserved.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation (1) indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost) or clearly do not. Weak recommendations (2) indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for postoperative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B), targeting a blood glucose < 150 mg/dL after initial stabilization (2C); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); and a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSIONS: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.