The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent. The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited. A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink). Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population–intervention–comparison–outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention.

https://erj.ersjournals.com/content/erj/50/3/1700582.full.pdf

International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia

Sepsis is a serious clinical condition that represents a patient’s response to a severe infection and has a very high mortality rate. Normal immune and physiologic responses eradicate pathogens, and the pathophysiology of sepsis is due to the inappropriate regulation of these normal reactions. In an ideal scenario, the first pathogen contact with the inflammatory system should eliminate the microbe and quickly return the host to homeostasis. The septic response may accelerate due to continued activation of neutrophils and macrophages/monocytes. Upregulation of lymphocyte costimulatory molecules and rapid lymphocyte apoptosis, delayed apoptosis of neutrophils, and enhanced necrosis of cells/tissues also contribute to the pathogenesis of sepsis. The coagulation system is closely tied to the inflammatory response, with cross talk between the two systems driving the dysregulated response. Biomarkers may be used to help diagnose patients with sepsis, and they may also help to identify patients who would benefit from immunomodulatory therapies.

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The Pathogenesis of Sepsis

The set of guidelines for good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents, which was developed following an international consensus conference in Copenhagen, has been revised and updated following the second consensus conference in Stockholm in 2005. It is hoped that these guidelines will continue to help researchers in the field and assist the pharmaceutical industry and equipment manufacturers in enhancing the standards of the studies they sponsor.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1399-6576.2007.01352.x

Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision.

Objective:The use of procalcitonin (ProCT) as a marker of several clinical conditions, in particular, systemic inflammation, infection, and sepsis, will be clarified, and its current limitations will be delineated. In particular, the need for a more sensitive assay will be emphasized. For these purp

Procalcitonin assay in systemic inflammation, infection, and sepsis: clinical utility and limitations.

OBJECTIVE To determine whether limiting intraoperative sedation depth during spinal anesthesia for hip fracture repair in elderly patients can decrease the prevalence of postoperative delirium. PATIENTS AND METHODS We performed a double-blind, randomized controlled trial at an academic medical center of elderly patients (≥65 years) without preoperative delirium or severe dementia who underwent hip fracture repair under spinal anesthesia with propofol sedation. Sedation depth was titrated using processed electroencephalography with the bispectral index (BIS), and patients were randomized to receive either deep (BIS, approximately 50) or light (BIS, ≥80) sedation. Postoperative delirium was assessed as defined by Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) criteria using the Confusion Assessment Method beginning at any time from the second day after surgery. RESULTS From April 2, 2005, through October 30, 2008, a total of 114 patients were randomized. The prevalence of postoperative delirium was significantly lower in the light sedation group (11/57 [19%] vs 23/57 [40%] in the deep sedation group; P =.02), indicating that 1 incident of delirium will be prevented for every 4.7 patients treated with light sedation. The mean ± SD number of days of delirium during hospitalization was lower in the light sedation group than in the deep sedation group (0.5±1.5 days vs 1.4±4.0 days; P =.01). CONCLUSION The use of light propofol sedation decreased the prevalence of postoperative delirium by 50% compared with deep sedation. Limiting depth of sedation during spinal anesthesia is a simple, safe, and cost-effective intervention for preventing postoperative delirium in elderly patients that could be widely and readily adopted. Trial Registration: www.clinicaltrials.gov Identifier: NCT00590707

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Sedation Depth During Spinal Anesthesia and the Development of Postoperative Delirium in Elderly Patients Undergoing Hip Fracture Repair

Since its introduction in 1996, the Bispectral Index (BIS) has gained increasing popularity in daily anesthesia practice. However, numerous reports have been appearing in the literature of paradoxical BIS changes and inaccurate readings. The purpose of this review is to assess the utility of BIS monitoring through examining the various published reports of all BIS values not coinciding with a clinically judged sedative-hypnotic state, whether arising from an underlying pathophysiology of electroencephalographic (EEG) cerebral function or because of shortcomings in the performance and design of the BIS monitor. High electromyographic activity and electric device interference could create subtle artifact signal pollution without their necessarily being displayed as artifacts. This would be misinterpreted by the BIS algorithm as EEG activity and assigned a spuriously increased BIS value. Numerous clinical conditions that have a direct effect on EEG cerebral function could also directly influence the BIS value.

Different conditions that could result in the bispectral index indicating an incorrect hypnotic state.

Facial electromyographic activity and neuromuscular block could influence bispectral index (BIS) depth of anesthesia monitoring. In this study we examined, in 30 patients undergoing general surgical procedures, the effect of different stages of neuromuscular block on BIS monitoring and compared the

The effect of different stages of neuromuscular block on the bispectral index and the bispectral index-XP under remifentanil/propofol anesthesia.

Methods. More than a period of 2 yr, subsets of 69 postoperative patients admitted with severe sepsis and 890 non-septic ICU patients were investigated. PCT, C-reactive protein (CRP) and sequential organ failure assessment (SOFA) score were recorded over the duration of ICU stay. Results. PCT area under receiver operating characteristic (ROC) curve was 0.78 on day 3 and was highly predictive of fatal outcome (0.90) at day 6. Area under ROC curve of SOFA score was 0.85 on day 3 and remained in this range until day 6. Area under ROC curves on day 3 of CRP (0.61) was non-predictive and remained non-predictive over the duration of ICU stay. Conclusions. PCT exhibited no discriminative power early after ICU admission for prediction of mortality in critically ill patients with severe sepsis, compared with a high predictive power of SOFA score on day 3. However, using PCT could still serve as a useful complementary comparator for prediction of survival outcome using the SOFA score. Br J Anaesth 2006; 97: 503–8

Procalcitonin for early prediction of survival outcome in postoperative critically ill patients with severe sepsis

The neuromuscular transmission module (M-NMT) is an integrated piezoelectric motion sensor module incorporated in the AS/3™ anesthesia monitor We compared the neuromuscular block of 06 mg/kg rocuronium (twice the 95% effective dose) monitored by the M-NMT with that monitored by the Relaxometer® me

The Neuromuscular Transmission Module Versus the Relaxometer Mechanomyograph for Neuromuscular Block Monitoring

Procalcitonin (PCT), interleukin-6 (IL-6), tumour necrosis factor a (TNFalpha), and interleukin-1beta (IL-1beta) are important clinical prognostic markers in ICU septic patients. The goal of the study was to determine whether continuous venovenous haemofiltration (CWH), using an AN69 haemofilte, leads to elimination of PCT, TNFalpha, IL-6 and IL-1beta in 13 septic patients with multi-organ failure. At the start of haemofiltration (0), 6 and 12 hours the mean afferent plasma concentration +/- SD of PCT (10.1 +/- 9.1, 7 +/- 6, 5.9 +/- 5.7 ng/ml), IL-6 (804.6 +/- 847.6, 611.7 +/- 528.4, 575.2 +/- 539.2 pg/ml), and that of TNFalpha (4.5 +/- 2.6, 4 +/- 3.1, 3.8 +/- 2.9 pg/ml) significantly declined during CVVH. The efferent plasma concentrations were significantly lower than the corresponding afferent concentrations. PCT; IL-6 and TNFalpha were detectable in the ultrafiltrate of all patients. IL-1beta was only detectable in the plasma of eight patients and the ultrafiltrate of five patients. The plasma clearance of PCT, IL-6 and TNFalpha significantly decreased after 12 hours as a result of a decline in the adsorptive elimination of the mediators due to progressive membrane saturation. We demonstrated that if PCT, IL-6 and TNFalpha are used as clinical prognostic markers in septic patients who are treated with CWIH using an AN69 membrane, one should be aware that their plasma level could be modified by the therapy. In addition CWH could represent an appropriate tool to remove a broad spectrum of proinflammatory mediators, if such removal is required in septic patients.

Ashraf A Dahaba

Papers

Different conditions that could result in the bispectral index indicating an incorrect hypnotic state.

The effect of different stages of neuromuscular block on the bispectral index and the bispectral index-XP under remifentanil/propofol anesthesia.

Procalcitonin for early prediction of survival outcome in postoperative critically ill patients with severe sepsis

The Neuromuscular Transmission Module Versus the Relaxometer Mechanomyograph for Neuromuscular Block Monitoring

Procalcitonin and proinflammatory cytokine clearance during continuous venovenous haemofiltration in septic patients.