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Background: By controlling hypercapnia, respiratory acidosis, and associated consequences, extracorporeal CO 2 removal (ECCO 2 R) has the potential to facilitate ultra-protective lung ventilation (UPLV) strategies and to decrease injury from mechanical ventilation. We convened a meeting of European intensivists and nephrologists and used a modified Delphi process to provide updated insights into the role of ECCO 2 R in acute respiratory distress syndrome (ARDS) and to identify recommendations for a future randomized controlled trial., Results: The group agreed that lung protective ventilation and UPLV should have distinct definitions, with UPLV primarily defined by a tidal volume (V T ) of 4-6 mL/kg predicted body weight with a driving pressure (ΔP) ≤ 14-15 cmH 2 O. Fourteen (93%) participants agreed that ECCO 2 R would be needed in the majority of patients to implement UPLV. Furthermore, 10 participants (majority, 63%) would select patients with PaO 2 :FiO 2  > 100 mmHg (> 13.3 kPa) and 14 (consensus, 88%) would select patients with a ventilatory ratio of > 2.5-3. A minimum CO 2 removal rate of 80 mL/min delivered by continuous renal support machines was suggested (11/14 participants, 79%) for this objective, using a short, double-lumen catheter inserted into the right internal jugular vein as the preferred vascular access. Of the participants, 14/15 (93%, consensus) stated that a new randomized trial of ECCO 2 R is needed in patients with ARDS. A ΔP of ≥ 14-15 cmH 2 O was suggested by 12/14 participants (86%) as the primary inclusion criterion., Conclusions: ECCO 2 R may facilitate UPLV with lower volume and pressures provided by the ventilator, while controlling respiratory acidosis. Since recent European Society of Intensive Care Medicine guidelines on ARDS recommended against the use of ECCO 2 R for the treatment of ARDS outside of randomized controlled trials, new trials of ECCO 2 R are urgently needed, with a ΔP of ≥ 14-15 cmH 2 O suggested as the primary inclusion criterion., (© 2024. The Author(s).)

Background: Electrical Impedance Tomography (EIT), combined with variable ventilation strategies and Artificial Intelligence (AI), is poised to revolutionize critical care by transitioning from reactive to predictive approaches. This integration aims to enhance patient outcomes through personalized interventions and real-time monitoring., Methods: this narrative review explores the principles and applications of EIT, variable ventilation, and AI in critical care. EIT impedance sensing creates dynamic images of internal physiology, aiding the management of conditions like Acute Respiratory Distress Syndrome (ARDS). Variable ventilation mimics natural breathing variability to improve lung function and minimize ventilator-induced lung injury. AI enhances EIT through advanced image reconstruction techniques, neural networks, and digital twin technology, offering more accurate diagnostics and tailored therapeutic interventions., Conclusions: the confluence of EIT, variable ventilation, and AI represents a significant advancement in critical care, enabling a predictive, personalized approach. EIT provides real-time insights into lung function, guiding precise ventilation adjustments and therapeutic interventions. AI integration enhances EIT diagnostic capabilities, facilitating the development of personalized treatment plans. This synergy fosters interdisciplinary collaborations and sets the stage for innovative research, ultimately improving patient outcomes and advancing the future of critical care.

Background: Mechanical ventilation significantly improves patient survival but is associated with complications, increasing healthcare costs and morbidity. Identifying optimal weaning times is paramount to minimize these risks, yet current methods rely heavily on clinical judgment, lacking specificity., Methods: This study introduces a novel multiparametric predictive score, the MUSVIP (MUltiparametric Score for Ventilation discontinuation in Intensive care Patients), aimed at accurately predicting successful extubation. Conducted at Santo Stefano Hospital's ICU, this single-center, observational, prospective cohort study will span over 12 months, enrolling adult patients undergoing invasive mechanical ventilation. The MUSVIP integrates variables measured before and during a spontaneous breathing trial (SBT) to formulate a predictive score., Results: Preliminary analyses suggest an Area Under the Curve (AUC) of 0.815 for the MUSVIP, indicating high predictive capacity. By systematically applying this score, we anticipate identifying patients likely to succeed in weaning earlier, potentially reducing ICU length of stay and associated healthcare costs., Conclusion: This study's findings could significantly influence clinical practices, offering a robust, easy-to-use tool for optimizing weaning processes in ICUs.

Introduction: The management of severe COVID-19-induced acute respiratory distress syndrome (C-ARDS) often involves deep sedation. This study evaluated the efficacy of sevoflurane, a volatile anesthetic, as an alternative to traditional intravenous sedation in this patient population., Methods: This single-center, retrospective cohort study enrolled 112 patients with C-ARDS requiring invasive mechanical ventilation. A propensity score matching model was utilized to pair 56 patients receiving sevoflurane sedation with 56 patients receiving intravenous sedation. The primary outcome was mortality, with secondary outcomes being changes in oxygenation (PaO2/FiO2 ratio), pulmonary compliance, and levels of D-Dimer, CRP, and creatinine., Results: The use of sevoflurane was associated with a statistically significant reduction in mortality (OR 0.40, 95% CI 0.18-0.87, beta = -0.9, p = 0.02). In terms of secondary outcomes, an increase in the PaO2/FiO2 ratio and pulmonary static compliance was observed, although the results were not statistically significant. No significant differences were noted in the levels of D-Dimer, CRP, and creatinine between the two groups., Conclusion: Our findings suggest an association between the use of sevoflurane and improved outcomes in C-ARDS patients requiring invasive mechanical ventilation. However, due to the single-center, retrospective design of the study, caution should be taken in interpreting these results, and further research is needed to corroborate these findings. The study offers promising insights into potential alternative sedation strategies in the management of severe C-ARDS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Consales, Cappellini, Freschi, Campiglia, Parise and Zamidei.)

Background: Septoplasty, a common surgical procedure to correct a deviated septum, can be performed under either general anesthesia or deep sedation anesthesia. The choice of anesthesia can influence the duration of anesthesia and surgical outcomes, impacting the feasibility of outpatient procedures., Methods: The institutional review board approved the protocol, and we obtained written informed consent from all participants. This retrospective, single-center observational study analyzed data from 586 patients who underwent rhino septoplasty at Santo Stefano Hospital in Prato, Italy, from 2017 to 2021. Patients received either general anesthesia or deep sedation anesthesia. Propensity score matching and inverse probability weighting were used to balance patient characteristics. The main outcome variable was discharge time, with anesthesia time and surgical time as covariates. Statistical analysis was conducted using R software., Results: Patients who received deep sedation anesthesia had a significantly shorter duration of anesthesia compared to those who received general anesthesia. A multivariate linear regression model showed that the type of anesthesia had a strong positive association with discharge time, while anesthesia time had a weaker negative association, although not statistically significant., Conclusions: Deep sedation anesthesia is associated with a shorter duration of anesthesia compared to general anesthesia during nasal septal surgery, suggesting it could be a more feasible option for outpatient procedures. However, the choice of anesthesia should be tailored to individual patient factors and surgical requirements. Further research is needed to confirm these findings and explore the potential benefits of sedation anesthesia in outpatient nasal septal surgery., Question: How do general anesthesia and deep sedation anesthesia compare in terms of duration of anesthesia and surgical outcomes during nasal septal surgery?, Findings: Our study found that deep sedation anesthesia was associated with a shorter duration of anesthesia compared to general anesthesia in patients undergoing nasal septal surgery. However, there were no significant differences in the duration of the surgical procedure., Meaning: The findings suggest that deep sedation anesthesia could potentially make nasal septal surgery more feasible as an outpatient procedure., (© 2023. Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care.)

Background: Critically ill patients with acute respiratory failure frequently present concomitant lung and kidney injury, within a multiorgan failure condition due to local and systemic mediators. To face this issue, extracorporeal carbon dioxide removal (ECCO2R) systems have been integrated into continuous renal replacement therapy (CRRT) platforms to provide a combined organ support, with efficient clearance of CO2 with very low extracorporeal blood flows (<400 mL/min)., Objectives: To evaluate efficacy and safety of combined ECCO2R-CRRT support with PrismaLung®-Prismaflex® in patients affected by hypercapnic respiratory acidosis associated with AKI in a second level intensive care unit., Methods: We carried out a retrospective observational study enrolling patients submitted to PrismaLung®-Prismaflex® due to mild to moderate acute respiratory distress syndrome (ARDS) or acute exacerbation of chronic obstructive pulmonary disease (aeCOPD). The primary endpoints were the shift to protective ventilation and extubation of mechanically ventilated patients and the shift to invasive mechanical ventilation of patients receiving noninvasive ventilation (NIV). Clinical-laboratoristic data and operational characteristics of ECCO2R-CRRT were recorded., Results: Overall, 12/17 patients on mechanical ventilation shifted to protective ventilation, CO2 clearance was satisfactorily maintained during the whole observational period, and pH was rapidly corrected. Treatment prevented NIV failure in 4 out of 5 patients. No treatment-related complications were recorded., Conclusion: ECCO2R-CRRT was effective and safe in patients with aeCOPD and ARDS associated with AKI., (© 2021 S. Karger AG, Basel.)

Triage is crucial for patient's management and estimation of the required intensive care unit (ICU) beds is fundamental for health systems during the COVID-19 pandemic. We assessed whether chest computed tomography (CT) of COVID-19 pneumonia has an incremental role in predicting patient's admission to ICU. We performed volumetric and texture analysis of the areas of the affected lung in CT of 115 outpatients with COVID-19 infection presenting to the emergency room with dyspnea and unresponsive hypoxyemia. Admission blood laboratory including lymphocyte count, serum lactate dehydrogenase, D-dimer and C-reactive protein and the ratio between the arterial partial pressure of oxygen and inspired oxygen were collected. By calculating the areas under the receiver-operating characteristic curves (AUC), we compared the performance of blood laboratory-arterial gas analyses features alone and combined with the CT features in two hybrid models (Hybrid radiological and Hybrid radiomics)for predicting ICU admission. Following a machine learning approach, 63 patients were allocated to the training and 52 to the validation set. Twenty-nine (25%) of patients were admitted to ICU. The Hybrid radiological model comprising the lung %consolidation performed significantly (p = 0.04) better in predicting ICU admission in the validation (AUC = 0.82; 95% confidence interval 0.73-0.97) set than the blood laboratory-arterial gas analyses features alone (AUC = 0.71; 95% confidence interval 0.56-0.86). A risk calculator for ICU admission was derived and is available at: https://github.com/cgplab/covidapp . The volume of the consolidated lung in CT of patients with COVID-19 pneumonia has a mild but significant incremental value in predicting ICU admission., (© 2021. The Author(s).)

Background: Prone positioning (PP) has been used to improve oxygenation in patients affected by the SARS-CoV-2 disease (COVID-19). Several mechanisms, including lung recruitment and better lung ventilation/perfusion matching, make a relevant rational for using PP. However, not all patients maintain the oxygenation improvement after returning to supine position. Nevertheless, no evidence exists that a sustained oxygenation response after PP is associated to outcome in mechanically ventilated COVID-19 patients. We analyzed data from 191 patients affected by COVID-19-related acute respiratory distress syndrome undergoing PP for clinical reasons. Clinical history, severity scores and respiratory mechanics were analyzed. Patients were classified as responders (≥ median PaO 2 /FiO 2 variation) or non-responders (< median PaO 2 /FiO 2 variation) based on the PaO 2 /FiO 2 percentage change between pre-proning and 1 to 3 h after re-supination in the first prone positioning session. Differences among the groups in physiological variables, complication rates and outcome were evaluated. A competing risk regression analysis was conducted to evaluate if PaO 2 /FiO 2 response after the first pronation cycle was associated to liberation from mechanical ventilation., Results: The median PaO 2 /FiO 2 variation after the first PP cycle was 49 [19-100%] and no differences were found in demographics, comorbidities, ventilatory treatment and PaO 2 /FiO 2 before PP between responders (96/191) and non-responders (95/191). Despite no differences in ICU length of stay, non-responders had a higher rate of tracheostomy (70.5% vs 47.9, P = 0.008) and mortality (53.7% vs 33.3%, P = 0.006), as compared to responders. Moreover, oxygenation response after the first PP was independently associated to liberation from mechanical ventilation at 28 days and was increasingly higher being higher the oxygenation response to PP., Conclusions: Sustained oxygenation improvement after first PP session is independently associated to improved survival and reduced duration of mechanical ventilation in critically ill COVID-19 patients.

Introduction: Cardiogenic shock is a condition of low cardiac output that represents the end stage of a progressive deterioration of cardiac function. The main cause is ischaemic heart disease, but there are several non-ischaemic causes, including sepsis. The use of levosimendan in cardiogenic shock during sepsis is still under debate., Methods: We are conducting an observational, single-centre, not-for-profit study enrolling patients aged 18-80 years old admitted to the intensive care unit with a diagnosis of septic shock. Patients will be monitored with the EV1000/VolumeView device (Edwards Lifesciences, Irvine, USA). Patients with cardiac index (CI) values <2.5 L/min/m 2 and/or stroke volume index (SVI) <30 mL/beat/m 2 are considered eligible for the study. Enrolled participants will undergo an echocardiographic examination using the Vivid S6 ultrasound machine (General Electric, Northville, Michigan) and a 3.6 MHz cardiology probe through which the apical projections of chambers 2, 3 and 4 will be acquired; this is necessary to calculate the global longitudinal strain (GLS) using EchoPAC* Clinical Workstation Software (General Electric). A dobutamine infusion will be started in these patients; 24 hours later CI and SVI will be recalculated using EV1000/VolumeView and then a levosimendan infusion will begin for 24 hours. Once the infusion cycle of the calcium-sensitising drug has been carried out, the infusion of dobutamine will be reduced until it stops, and the CI, SVI, GLS and arterial elastance (Ea):Ventricular Elastance (Ees) will be re-evaluated. The primary endpoint is recovery of GLS ≥15% and the secondary endpoint is a relative reduction in mortality of 15%., Ethics and Dissemination: The investigators declare that the study will be conducted in full compliance with international regulations (EU Directive 2016/679/EC) and national implementation (DM 15 July 1997; 211/2003; 200/2007) regarding the clinical trial and the principles of the Declaration of Helsinki. Study results will be disseminated through peer-reviewed journals and conferences. Ethical approval for this study has been given by Comitato Etico Regione Toscana - Area Vasta Centro, Florence, Italy (ethical committee number: 13875&#95;oss) on 25 May 2019 (Chairperson Professor Marco Marchi)., Trial Registration Number: NCT04141410., Competing Interests: Competing interests: This trial has been designed independently of any commercial organisation and will be independently coordinated, managed and analysed., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: With recent advances in technology, patients with acute respiratory distress syndrome (ARDS) and severe acute exacerbations of chronic obstructive pulmonary disease (ae-COPD) could benefit from extracorporeal CO 2 removal (ECCO 2 R). However, current evidence in these indications is limited. A European ECCO 2 R Expert Round Table Meeting was convened to further explore the potential for this treatment approach., Methods: A modified Delphi-based method was used to collate European experts' views to better understand how ECCO 2 R therapy is applied, identify how patients are selected and how treatment decisions are made, as well as to identify any points of consensus., Results: Fourteen participants were selected based on known clinical expertise in critical care and in providing respiratory support with ECCO 2 R or extracorporeal membrane oxygenation. ARDS was considered the primary indication for ECCO 2 R therapy (n = 7), while 3 participants considered ae-COPD the primary indication. The group agreed that the primary treatment goal of ECCO 2 R therapy in patients with ARDS was to apply ultra-protective lung ventilation via managing CO 2 levels. Driving pressure (≥ 14 cmH 2 O) followed by plateau pressure (P plat ; ≥ 25 cmH 2 O) was considered the most important criteria for ECCO 2 R initiation. Key treatment targets for patients with ARDS undergoing ECCO 2 R included pH (> 7.30), respiratory rate (< 25 or < 20 breaths/min), driving pressure (< 14 cmH 2 O) and P plat (< 25 cmH 2 O). In ae-COPD, there was consensus that, in patients at risk of non-invasive ventilation (NIV) failure, no decrease in PaCO 2 and no decrease in respiratory rate were key criteria for initiating ECCO 2 R therapy. Key treatment targets in ae-COPD were patient comfort, pH (> 7.30-7.35), respiratory rate (< 20-25 breaths/min), decrease of PaCO 2 (by 10-20%), weaning from NIV, decrease in HCO 3 - and maintaining haemodynamic stability. Consensus was reached on weaning protocols for both indications. Anticoagulation with intravenous unfractionated heparin was the strategy preferred by the group., Conclusions: Insights from this group of experienced physicians suggest that ECCO 2 R therapy may be an effective supportive treatment for adults with ARDS or ae-COPD. Further evidence from randomised clinical trials and/or high-quality prospective studies is needed to better guide decision making.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates pro-thrombotic changes. This, combined with its tropism for endothelium and lung structures, may explain its association with thrombotic events, reduction of pulmonary gas exchange, acute respiratory distress syndrome (ARDS) and a composite end-point (intensive care unit, invasive ventilation, death). This study aims to highlight the correlation between elevated D-dimer (an indirect thrombosis marker) and the increased rate of poor prognosis-associated conditions, and to introduce D-dimer-labelled anticoagulant administration as a potentially useful tool to prevent complications and positively influence coronavirus disease 2019 (COVID-19) course., Methods: An online database search (PubMed, Google Scholar, Scopus, Web of Science and Cochrane) was performed between 13 March and 10 April 2020. The most relevant keywords were "D-dimer", "SARS-CoV-2", "COVID-19", "thrombosis" and "ARDS". Selection was independently conducted by three reviewers. References and previews of accepted articles were evaluated. Data inclusion/extraction inaccuracy was limited by the work of three reviewers. Selection bias reduction was addressed by thoughtfully designing the search protocol. Quality assessment was performed with the Newcastle-Ottawa Scale. The systematic review protocol was not registered because we anticipated the very limited available evidence on the topic and due to the urgency of the study., Results: 16 studies were evaluated. Good-quality criteria were reached in 13 out of 16 studies. D-dimer was increased and significantly higher in COVID-19 patients compared with healthy controls, in COVID-19 patients with severe disease or a composite end-point compared with non-severe disease, in ARDS compared with non-ARDS patients and in deceased ARDS patients compared with ARDS patients who survived (all p<0.001). COVID-19 patients treated with anticoagulants demonstrated lower mortality compared with those not treated (p=0.017)., Conclusions: Correlations exist between COVID-19 infection, severe elevation of D-dimer levels, and increase in the rate of complications and composite end-point. The appropriateness of early and continuous D-dimer monitoring and labelled anticoagulation as management tools for COVID-19 disease deserves accurate investigation, to prevent complications and reduce interventions., Competing Interests: Conflict of interest: S. Vidali has nothing to disclose. Conflict of interest: D. Morosetti has nothing to disclose. Conflict of interest: E. Cossu has nothing to disclose. Conflict of interest: M.L.E. Luisi has nothing to disclose. Conflict of interest: S. Pancani has nothing to disclose. Conflict of interest: V. Semeraro has nothing to disclose. Conflict of interest: G. Consales has nothing to disclose., (Copyright ©ERS 2020.)

We present the first Italian reported case of an invasive meningococcal disease with rifampicin-resistance (Rif-R)secondary to chemoprophylaxis. The case is entered in a cluster of two IMDs registered in Tuscany, Italy, in November 2019 caused by two non-differentiable group-C Neisseria meningitidis belonging to ST-11 clonal-complex. The contact case, differently from the index, harbored H552Y mutation on rpoB gene which is known to confer Rif-R putting a high-cost fee on bacterial fitness. The extremely mild clinical presentation in the contact can constitute an in vivo demonstration of the virulence attenuation observed in vitro for H552Ymutants. Clinicians should be aware of the possibility of secondary cases with induced Rif-R and keep a high level of suspicion on contacts who received rifampicin-chemoprophylaxis. Molecular characterization of Rif-R should be performed routinely directly on biological samples and not only on isolates, in order to rapidly detect rare cases of resistance and consequently modify chemoprophylaxis for contacts.

The 7-valent pneumococcal conjugate vaccine (PCV7) produced a significant herd protection in unvaccinated adult population mostly because of pneumococcus carriage decrease in vaccinated children. It is not known if the 13-valent pneumococcal vaccine can give similar effect on adults. Aims of the work were to evaluate whether the 6 additional serotypes are present in nasopharynx of children and serotype distribution in invasive pneumococcal infections (IPD) in adults. Realtime-PCR was used to evaluate pneumococcal serotypes in adults with confirmed IPD and in nasopharyngeal swabs (NP) from 629 children not vaccinated or vaccinated with PCV7 and resident in the same geographical areas. Two hundred twenty-one patients (116 males, median 67.9 years) with IPD were studied (pneumonia n = 103, meningitis n = 61 sepsis n = 50, other n = 7). Two hundred twelve were serotyped. The most frequent serotypes were 3, (31/212; 14.6%), 19A, (19/212; 9.0%), 12 (17/212; 8.0%), 7F, (14/212; 6.6%). In NP of children, the frequency of those serotypes causing over 50% of IPD in adults was very low, ranging from 0.48% for serotype 7F to 7.9% for serotype 19A. On the other side serotype 5, very frequent in NP (18.7%) caused <1% IPD. In conclusion serotypes causing IPD in adults are very rarely found in children NP. We suggest that herd protection obtainable with the additional 6 serotypes included in PCV13 may be more limited than that demonstrated with PCV7 in the past. In order to reduce the burden of disease in adults, adults should be offered a specific vaccination program with highly immunogenic PCV.

Background: Hemodialysis with high cut-off continuous veno-venous hemodialyzer (HCO-CVVHD) removes mediators of organ dysfunction during sepsis. This study assessed the clinical effects of HCO-CVVHD as compared to high-flux (HF) membranes during gram-negative sepsis., Methods: Intensive care unit (ICU), septic patients treated with HCO-CVVHD or HF-CVVHDF for AKI were retrospectively observed (January 2013-December 2014). Mechanical ventilation, vasopressors' requirements, ICU length of stay (LOS) and ICU in-hospital mortality were compared between groups., Results: Sixteen HCO and 8 HF patients were observed. Isolated pathogens included Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli and Pseudomonas aeruginosa. Median ratios of days-on-vasopressors and days-on-mechanical ventilation/ICU-LOS were 0.5, 1 and 0.8, 1 for HCO and HF groups (p < 0.03), respectively. ICU-LOS was 16 and 9 days (HCO- and HF-group, p = 0.03). ICU mortality rates were 37.5 and 87.5% for HCO and HF groups, respectively (p = 0.03). No statistical difference was found in in-hospital morality., Conclusion: Patients in HCO-CVVHD group spent lesser number of days on vasopressors and mechanical ventilation as a ratio to total ICU-LOS. In the same group, a reduction in ICU mortality was observed., (© 2016 S. Karger AG, Basel.)

Purpose: Multidrug-resistant Acinetobacter baumannii (MRAB) is an emerging cause of intensive care unit (ICU) outbreaks. Patients are the main reservoirs, inducing cross transmission. We describe an MRAB outbreak that occurred in the Prato Hospital ICU in June to August 2009., Materials and Methods: The ICU consists of 2 separated 4-bed rooms (rooms A and B). The MRAB-positive patients were included in our study. During the outbreak, infection control measures were enhanced; patients and environmental screenings were performed. A 6-month follow-up was carried out., Results: Four of 26 patients admitted during the outbreak were MRAB positive. All patients were located in room A; no case was detected in room B either in the hospital or during the follow-up. Management included closure to new admissions, reinforcement of infection control measures, patient and environmental screenings, discharge of room B MRAB-negative patients for at least 5 days after the first case identification. All isolates were carbapenems resistant and tigecycline and colistin susceptible. All patients received tigecycline: 2 were successfully treated, 1 died because of preexisting illness, and 1 developed resistance and recovered after colistin therapy., Conclusions: Enhanced infection control measures and adequate antibiotic strategy limited the outbreak. Tigecycline allowed rapid recovery. Nevertheless, resistance ensued; so colistin remained the only therapeutic option. However, pan-drug resistance has been reported., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Pain can play an important role at the social and psychological level; hence one of the major goals of anaesthesia is to control and reduce the incidence of postoperative pain. The use of an analgesia before surgical incision may offer one of the most innovative and promising strategies for better pain control throughout the perioperative period. Pre-emptive analgesia refers to pharmacological intervention initiated prior to a painful stimulus in order to inhibit nociceptive mechanisms before they are triggered. Pre-emptive analgesia has three objectives: to reduce pain resulting from the activation of inflammatory mechanisms triggered by surgical incision; to hinder the pain memory response of the central nervous system; and to ensure a good control of postoperative pain in order to avoid the development of chronic pain. The following provides an overview of the scientific rationale for pre-emptive analgesia alongside an overview of published systematic reviews and randomized clinical trials related to this topic.

Background: Treatment with analgesics before surgery may be effective in reducing post-operative pain. This approach is defined as "pre-emptive analgesia" and recent reviews show conflicting results., Objectives: The aim of this study was to investigate the efficacy of pre-emptive analgesia with sublingual morphine sulphate, compared with sublingual midazolam in patients undergoing elective abdominal surgery., Methods: Prior to surgery, 29 patients were randomized and premedicated with sublingual morphine sulphate 0.5 mg/kg (Group A; n = 15) or with sublingual midazolam 0.03 mg/kg (Group B; n = 14). General anaesthesia was maintained with sevoflurane and fentanyl. Post-operatively, intravenous (IV) acetaminophen 0.02 mg/kg was given to all patients and a bolus of IV morphine 0.1 mg/kg was given to Group B patients. Post-operative pain was controlled by IV morphine via a patient-controlled analgesia (PCA) device. IV acetaminophen 0.02 mg/kg was also administered four times daily. Efficacy was assessed using static Visual Analogue Scale (sVAS) scores, dynamic VAS (dVAS) scores, number of PCA doses administered and number of failed doses registered from the PCA device at 4, 6, 24 and 48 hours after surgery. Results were statistically analysed using the Student t-test; a value of p < 0.05 was considered significant., Results: Significantly lower sVAS and dVAS scores were observed in Group A patients than in Group B at all assessment periods (p < 0.05 for all time points). There were less PCA administered and failed doses in Group A, compared with Group B (all time points p < 0.05). There was no difference in the occurrence of common side effects between the two treatments., Conclusions: In patients undergoing elective abdominal surgery, premedication with sublingual morphine sulphate results in a better control of post-operative pain, compared to premedication with sublingual midazolam. The beneficial effect of pre-operative sublingual morphine sulphate was apparent in the immediate post-operative period and was sustained over the 48-hour assessment period.