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Objective: Sepsis is a complex inflammatory disease, rising in response to infection. Drotrecogin alfa, approved in 2001 for severe sepsis, has been withdrawn from the market. The aim of this study was to assess if drotrecogin alfa-activated can reduce mortality in the more severe septic patients. Methods: We searched PubMed, Embase, Scopus, BioMedCentral, and in Clinicaltrials. gov databases to identify every randomized study performed on drotrecogin alfa-activated in any clinical setting in humans, without restrictions on dose or time of administration. Our primary end-point was mortality rate in high risk patients. Secondary endpoints were mortality in all patients, in patients with an Acute Physiology and Chronic Health Evaluation (APACHE) 2 score ≥ 25 and in those with an APACHE 2 score ≤25. Results: Five trials were identified and included in the analysis. They randomized 3196 patients to drotrecogin alfa and 3111 to the control group. Drotrecogin alfa was associated with a reduction in mortality (99/263 [37.6%] vs 115/244 [47.1%], risk ratios (RR) = 0.80[0.65; 0.98], p = 0.03) in patients with multiple organ failure and a mortality risk in the control group of >40%, but not in the overall population or in lower risk populations. Conclusions: In high risk populations of patients with multiple organ failure and a mortality of >40% in the control group, Drotrecogin alfa may still have a role as a lifesaving treatment. No beneficial effect in low risk patients was found. An individual patient meta-analysis including all randomized controlled trial on sepsis is warranted, along with new studies on similar drugs such as protein C zymogen.

To estimate the effect of non-invasive mechanical ventilation (NIV) on the rate of reintubation among patients undergoing cardiothoracic surgery.A meta-analysis of randomised trials.Medline, Embase, and the Cochrane Central Register of clinical trials were searched (April 2012) for pertinent studies by two trained investigators. International experts were contacted.Articles were assessed by two trained investigators, with divergences resolved by consensus. Inclusion criterion was random allocation to NIV versus standard treatment without restrictions on duration or modalities of the treatment delivered.Fourteen studies enrolling 1211 patients were included in the meta-analysis. NIV reduced the reintubation rate (risk ratio [RR], 0.29; 95% CI, 0.16-0.53; P for efficacy0.0001; I2 = 0), hospital length of stay and mortality. Subgroup analyses suggested that the benefits of NIV are more important in patients with ongoing acute respiratory failure (RR, 0.25; 95% CI, 0.07-0.89) and in those at high risk of developing postoperative pulmonary complications (RR, 0.19; 95% CI, 0.04-0.84). Analyses including prophylactic studies in patients at low risk did not show a significant effect of NIV on reintubation rate (RR = 0.42; 95% CI, 0.12-1.48) and on any of the outcomes considered except for oxygenation.NIV seems to be effective in reducing reintubation rate after cardiothoracic surgery. The results of this meta-analysis should be confirmed by large randomised controlled studies.

Many studies have compared desflurane, isoflurane, sevoflurane, total i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on patient survival.We performed standard pairwise and Bayesian network meta-analyses; the latter allows indirect assessments if any of the anaesthetic agents were not compared in head-to-head trials. Pertinent studies were identified using BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in June 2012).We identified 38 randomized trials with survival data published between 1991 and 2012, with most studies (63%) done in coronary artery bypass grafting (CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis showed that the use of a volatile agent was associated with a reduction in mortality when compared with TIVA at the longest follow-up available [25/1994 (1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio (OR)=0.51, 95% confidence interval (CI) 0.33-0.81, P-value for effect=0.004, number needed to treat 74, I(2)=0%] with results confirmed in trials with low risk of bias, in large trials, and when including only CABG studies. Bayesian network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval 0.14-0.64) and desflurane (OR=0.43, 95% credible interval 0.21-0.82) were individually associated with a reduction in mortality when compared with TIVA.Anaesthesia with volatile agents appears to reduce mortality after cardiac surgery when compared with TIVA, especially when sevoflurane or desflurane is used. A large, multicentre trial is warranted to confirm that long-term survival is significantly affected by the choice of anaesthetic.

ObjectiveStatins are among the most prescribed drugs worldwide and their recently discovered anti-inflammatory effect seems to have an important role in inhibiting proinflammatory cytokine production, chemokines expression and counteracting the harmful effects of sepsis on the coagulation system. We decided to perform a meta-analysis of all randomized controlled trials ever published on statin therapy in septic patients to evaluate their effect on survival and length of hospital stay.Data sources and study selectionArticles were assessed by four trained investigators, with divergences resolved by consensus. BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and comparison of statins versus any comparator in septic patients.Data extraction and synthesisData from 650 patients in 5 randomized controlled studies were analyzed. No difference in mortality between patients receiving statins versus control (44/322 [14%] in the statins group vs 50/328 [15%] in the control arm, RR = 0.90 [95% CI 0.65 to 1.26], p = 0.6) was observed. No differences in hospital stay (p = 0.7) were found.ConclusionsPublished data show that statin therapy has no effect on mortality in the overall population of adult septic patients. Scientific evidence on statins role in septic patients is still limited and larger randomized trials should be performed on this topic.

The diaphragm is the most important inspiratory muscle. It is dome-shaped, with the crural portion inserted on the anterior portions of lumbar vertebrae 1 through 3, and the costal portion inserted on the xiphoid process and the upper, inner margins of the lower six ribs. The majority of the muscular portion of the diaphragm lies directly beside the lower rib cage, referred to as the zone of apposition (ZOA) (Fig. 1a).

Objective The authors conducted a review of randomized studies to show whether there are any increases or decreases in survival when using milrinone in patients undergoing cardiac surgery. Design A meta-analysis. Setting Hospitals. Participants Five hundred eighteen patients from 13 randomized trials. Interventions None. Measurements and Main Results BioMedCentral, PubMed EMBASE, the Cochrane central register of clinical trials, and conference proceedings were searched for randomized trials that compared milrinone versus placebo or any other control in the setting of cardiac surgery that reported data on mortality. Overall analysis showed that milrinone increased perioperative mortality (13/249 [5.2%] in the milrinone group v 6/269 [2.2%] in the control arm, odds ratio [OR] = 2.67 [1.05-6.79], p for effect = 0.04, p for heterogeneity = 0.23, I2 = 25% with 518 patients and 13 studies included). Subanalyses confirmed increased mortality with milrinone (9/84 deaths [10.7%] v 3/105 deaths [2.9%] with other drugs as control, OR = 4.19 [1.27-13.84], p = 0.02) with 189 patients and 5 studies included) but did not confirm a difference in mortality (4/165 [2.4%] in the milrinone group v 3/164 [1.8%] with placebo or nothing as control, OR = 1.27 [0.28-5.84], p = 0.76 with 329 patients and 8 studies included). Conclusions This analysis suggests that milrinone might increase mortality in adult patients undergoing cardiac surgery. The effect was seen only in patients having an active inotropic drug for comparison and not in the placebo subgroup. Therefore, the question remains whether milrinone increased mortality or if the control inotropic drugs were more protective.

"OBJECTIVE: With more than 220 million major surgical procedures performed annually, perioperative interventions leading to even minor mortality reductions would save thousands of lives per year. This international consensus conference aimed to identify all nonsurgical interventions that increase or reduce perioperative mortality as suggested by randomized evidence.. . DESIGN AND SETTING: A web-based international consensus conference.. . PARTICIPANTS: More than 1,000 physicians from 77 countries participated in this web-based consensus conference.. . INTERVENTIONS: Systematic literature searches (MEDLINE\/PubMed, June 8, 2011) were used to identify the papers with a statistically significant effect on mortality together with contacts with experts. Interventions were considered eligible for evaluation if they (1) were published in peer-reviewed journals, (2) dealt with a nonsurgical intervention (drug\/technique\/strategy) in adult patients undergoing surgery, and (3) provided a statistically significant mortality increase or reduction as suggested by a randomized trial or meta-analysis of randomized trials.. . MEASUREMENTS AND MAIN RESULTS: Fourteen interventions that might change perioperative mortality in adult surgery were identified. Interventions that might reduce mortality include chlorhexidine oral rinse, clonidine, insulin, intra-aortic balloon pump, leukodepletion, levosimendan, neuraxial anesthesia, noninvasive respiratory support, hemodynamic optimization, oxygen, selective decontamination of the digestive tract, and volatile anesthetics. In contrast, aprotinin and extended-release metoprolol might increase mortality.. . CONCLUSIONS: Future research and health care funding should be directed toward studying and evaluating these interventions.. . "

BACKGROUND: Noninvasive ventilation (NIV) is increasingly utilized outside the ICU for patients with acute respiratory failure. However, success and failure risk factors and patient safety aspects have been poorly explored in this setting. So far, no study has evaluated the perspective of the patient, despite the known high relevance of patient participation for NIV success. METHODS: We prospectively interviewed (following a standard questionnaire) the patients successfully treated with NIV for acute respiratory failure outside the ICU. Subjects were interviewed 24–48 hours after NIV suspension. Exclusion criteria: NIV failure, patient not competent, patient unwilling to participate in the study, patient transferred to the ICU. RESULTS: Forty-five consecutive patients were included in the study. Only 20% participated in the initial setting of NIV parameters. More than 40% reported they never had the possibility to discuss the NIV treatment. Eighty percent reported they were never asked to try another interface. All subjects knew how to call for help, but only one fourth had been trained to remove the mask, and 22% reported not being able at all to remove the mask if needed. One half of the subjects reported having received help immediately when needed, but 15% waited more than 3 min. All subjects reported complications, and 18% reported respiratory worsening while on NIV. CONCLUSIONS: Subjects reported a low level of involvement in the initial setting of NIV treatment, low satisfaction about communication with the caring staff, and a suboptimal safety level in case of emergency.

Non-invasive ventilation (NIV), including both non-invasive positive pressure ventilation (NPPV) and non-invasive continuous positive airway pressure (CPAP), is increasingly applied to prevent or to treat acute respiratory failure [1]. Evidence of benefit has been demonstrated in some common diseases, such as chronic obstructive pulmonary disease (COPD) exacerbations, acute respiratory failure in immunosuppressed patients, and cardiogenic pulmonary edema. There is still no strong scientific evidence on the usefulness of NIV in other settings and more research is required [1, 2]. Nevertheless, NIV is an established, relevant option in the management of acute respiratory failure and the number of publications on this topic is steadily increasing (Fig. 1).

"Introduction. Acute renal failure and fluid retention are common problems in pediatric patients after cardiac surgery. Furosemide, a loop diuretic drug, is frequently administered to increase urinary output. The aim of the present study was to compare efficacy and complications of continuous infusion of furosemide vs bolus injection among pediatric patients after cardiac surgery. Methods. A systematic review and meta-analysis was performed in compliance with The Cochrane Collaboration and the Quality of Reporting of Meta-Analysis (QUORUM) guidelines. The following inclusion criteria were employed for potentially relevant studies: a) random treatment allocation, b) comparison of furosemide bolus vs continuous infusion, c) surgical or intensive care pediatric patients. Non-parallel design randomized trials (e.g. cross-over), duplicate publications and non-human experimental studies were excluded. Results. Up to August 2008, only three studies were found, with 92 patients randomized (50 to continuous infusion and 42 to bolus treatment). Overall analysis showed that continuous infusion and bolus administration were equally effective in achieving the predefined urinary output, and were associated with a similar amount of administered furosemide (WMD=- 1.71 mg/kg/day [-5.20; +1.78], p for effect=0.34, p for heterogeneity

"OBJECTIVE: Because at present no pharmacologic prevention or treatment of acute kidney injury seems to be available, the authors updated a meta-analysis to investigate the effects of fenoldopam in reducing acute kidney injury in patients undergoing cardiac surgery, focusing on randomized placebo-controlled studies only.. . DESIGN: A meta-analysis of randomized, placebo-controlled trials.. . SETTING: Hospitals.. . PARTICIPANTS: A total of 440 patients from 6 studies were included in the analysis.. . INTERVENTIONS: None. The ability of fenoldopam to reduce acute kidney injury in the perioperative period when compared with placebo was investigated.. . MEASUREMENTS AND MAIN RESULTS: Google Scholar and PubMed were searched (updated January 1, 2012). Authors and external experts were contacted. Pooled estimates showed that fenoldopam consistently and significantly reduced the risk of acute kidney injury (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.23-0.74; p = 0.003), with a higher rate of hypotensive episodes and\/or use of vasopressors (30\/109 [27.5%] v 21\/112 [18.8%]; OR = 2.09; 95% CI, 0.98-4.47; p = 0.06) and no effect on renal replacement therapy, survival, and length of intensive care unit or hospital stay.. . CONCLUSIONS: This analysis suggests that fenoldopam reduces acute kidney injury in patients undergoing cardiac surgery. Because the number of the enrolled patients was small and there was no effect on renal replacement therapy or survival, a large, multicenter, and appropriately powered trial is needed to confirm these promising results.. . "

"Introduction. Acute renal failure and fluid retention are common problems in pediatric patients after cardiac surgery. Furosemide, a loop diuretic drug, is frequently administered to increase urinary output. The aim of the present study was to compare efficacy and complications of continuous infusion of furosemide vs bolus injection among pediatric patients after cardiac surgery. Methods. A systematic review and meta-analysis was performed in compliance with The Cochrane Collaboration and the Quality of Reporting of Meta-Analysis (QUORUM) guidelines. The following inclusion criteria were employed for potentially relevant studies: a) random treatment allocation, b) comparison of furosemide bolus vs continuous infusion, c) surgical or intensive care pediatric patients. Non-parallel design randomized trials (e.g. cross-over), duplicate publications and non-human experimental studies were excluded. Results. Up to August 2008, only three studies were found, with 92 patients randomized (50 to continuous infusion and 42 to bolus treatment). Overall analysis showed that continuous infusion and bolus administration were equally effective in achieving the predefined urinary output, and were associated with a similar amount of administered furosemide (WMD=- 1.71 mg/kg/day [-5.20; +1.78], p for effect=0.34, p for heterogeneity

"B-type natriuretic peptide is a cardiac hormone that relaxes vascular smooth muscle and causes arterial dilatation. Nesiritide has been associated with increased urine output; reduced diuretic requirements; and suppression of aldosterone, endothelin, and norepinephrine. We have independently conducted the first systematic review and meta-analysis of randomized trials to determine the impact of nesiritide on renal replacement therapy and death in patients undergoing cardiac surgery. We performed a meta-analysis of 6 randomized controlled studies including 560 patients (280 receiving nesiritide and 280 assigned to the control group). Two unblinded reviewers selected randomized trials studying nesiritide in patients undergoing cardiac surgery. Nesiritide doses ranged from 0.005 mcg/kg/min to 0.01 mcg/kg/min. Nesiritide did not reduce postoperative creatinine peak values: -0.16 [-0.42, 0.10], p for effect=0.23, p for heterogeneity

Introduction. Fluid overload and a positive fluid balance are common in the intensive care unit (ICU). Furosemide is frequently administered to increase urine output. A bolus injection is the traditional mode of administration, but many concerns have been raised about possible intravascular volume fluctuations, toxicity and enhanced tolerance. Furosemide related adverse effects can be enhanced in critically ill patients. Continuous infusion should allow better hemodynamic stability, less side effects and an easier achievement of the desired diuretic effect. We performed a systematic review and meta-analysis to compare the effects and complications of continuous furosemide infusion with those of bolus injections in critically ill patients in the ICU. Methods. Studies were searched in PubMed (updated January 2009). Backward snowballing of included papers was performed. International experts were contacted for further studies. The inclusion criteria were: random allocation to treatment, comparison of furosemide bolus vs continuous infusion, performed in surgical or intensive care patients. The exclusion criteria were: non-parallel design randomized trials, duplicate publications, non-human experimental studies, no outcome data. Results. Four eligible randomized clinical trials were identified, including 129 patients (64 to continuous infusion and 65 to bolus treatment). Continuous perfusion was not associated with a significant reduction in risk of mortality as compared to bolus injection Conclusions. Furosemide in continuous perfusion was not associated with a significant reduction in risk of hospital mortality as compared to bolus administration in critically ill patients in ICU, but existing data are insufficient to confidently assess the best way to administer furosemide . Applying a protocol to drive furosemide therapy could be more relevant than the chosen mode of administration.

Aims Transoesophageal echocardiography (TEE) may require patient sedation, eventually leading to respiratory depression, a risky condition in severe cardiac disease. Non-invasive ventilation (NIV) has been applied during diagnostic manoeuvres, but its use during TEE has not been reported. We describe NIV-aided continuous TEE monitoring under sedation in the supine position in three consecutive orthopnoeic patients with severe aortic valve stenosis: two of them underwent percutaneous aortic valve implantation, and one underwent aortic valvuloplasty. Methods and results The TEE probe was passed through a hole performed with a surgical cutter in an NIV face-mask. Pulsoximetry, heart rate, arterial blood pressure, respiratory rate, arterial blood gases, patients' comfort, and patient's sedation were monitored throughout the procedure. Percutaneous aortic valve implantation procedures lasted almost 2 h, while the valvuloplasty procedure lasted 70 min. Non-invasive ventilation and continuous TEE were performed throughout the procedures without technical problems or respiratory or haemodynamic complications, and all patients felt always comfortable. Conclusion Non-invasive ventilation through a modified face-mask allowed to perform continuous TEE examination and to avoid tracheal intubation and general anaesthesia in three high-risk patients undergoing beating heart treatment of aortic valve stenosis.

Extraperitoneal endometriosis is the presence of ectopic, functional endometrium outside the peritoneal cavity, and its occurrence is exceedingly rare. Diagnostic imaging--including ultrasound, duplex ultrasonography, and magnetic resonance imaging--in the preoperative assessment of patients with suspected abdominal wall endometriosis (AWE) is helpful for detection and accurate determination of the extent of disease. The treatment of choice for AWE is surgical excision. In addition, medical therapies can be used. We present one case of AWE treated with percutaneous radiofrequency ablation under ultrasound guidance. There were no major complications, and the patient's symptoms improved. In selected patients, radiofrequency ablation can be used safely for the treatment of AWE; however, further studies are needed to confirm this hypothesis.

Severe sepsis and septic shock are leading causes of morbidity and mortality in the pediatric population. Unlike what is suggested for the adult population, recombinant human activated protein C (rhAPC) is contraindicated in children. Long before rhAPC was considered for use in pediatric patients, case reports appeared on the safe administration of protein C zymogen. Therefore, we conducted a systemic review of currently available data on protein C zymogen (PC) use among children affected by severe sepsis or septic shock. A total number of 13 case series or case reports and a dose-finding study were found on the use of PC in the pediatric intensive care unit, reporting on 118 treated children, with an overall survival of 84%. There was no bleeding complication, the only reported complication being a single mild allergic reaction. These studies show that PC is safe, not associated with bleeding and possibly useful for improving coagulation abnormalities of sepsis. Severe sepsis and septic shock are leading causes of morbidity and mortality in the pediatric population. Unlike what is suggested for the adult population, recombinant human activated protein C (rhAPC) is contraindicated in children. Long before rhAPC was considered for use in pediatric patients, case reports appeared on the safe administration of protein C zymogen. Therefore, we conducted a systemic review of currently available data on protein C zymogen (PC) use among children affected by severe sepsis or septic shock. A total number of 13 case series or case reports and a dose-finding study were found on the use of PC in the pediatric intensive care unit, reporting on 118 treated children, with an overall survival of 84%. There was no bleeding complication, the only reported complication being a single mild allergic reaction These studies show that PC is safe, not associated with bleeding and possibly useful for improving coagulation abnormalities of sepsis

To report data about “real-life” treatments with non-invasive ventilation for acute respiratory failure (ARF), managed outside intensive care units by anaesthesiologists acting as a medical emergency team. Observational study; prospectively collected data over a 6-month period in a single centre. Non-intensive wards in a University Hospital with 1,100 beds. Consecutive patients with ARF for whom a ventilatory support was indicated but tracheal intubation was not appropriated or immediately needed. None. Patient’s characteristics, safety data, short-term outcome and organizational aspects of 129 consecutive treatments were collected. The overall success rate was 77.5%, while 10.1% were intubated and 12.4% died (all of them were “do not attempt resuscitation” patients). The incidence of treatment failure varied greatly among different diseases. Complications were limited to nasal decubitus (5%), failure to accomplish the prescribed ventilatory program (12%), malfunction of the ventilator (2%) and excessive air leaks from face mask (2%) with no consequences for patients. Three patients became intolerant to NIV. The work-load for the MET was high but sustainable: on average NIV was applied to a new case every 34 h and more than three patients were simultaneously treated. Under the supervision of a MET, in our institution NIV could be applied in a wide variety of settings, outside the ICU, with a high success rate and with few complications.

Objectives: Vital organ hypoperfusion significantly contributes to the dismal survival rates observed with manual cardiopulmonary resuscitation after cardiac arrest. The impedance threshold device is a valve which reduces air entry into lungs during chest recoil between chest compressions, producing a potentially beneficial decrease in intrathoracic pressure and thus increasing venous return to the heart. This review provides an update on the impedance threshold device and underlines its effect on shortterm survival. Data Source: MedCentral, CENTRAL, PubMed, and conference proceedings were searched (updated March 27, 2007). Authors and external experts were contacted. Study Selections: Three unblinded reviewers selected randomized trials using an impedance threshold device in cardiopulmonary resuscitation of nontraumatic out-of-hospital cardiac arrests. Four reviewers independently abstracted patient, treatment and outcome data. Data Extraction: A total of 833 patients from five high quality randomized studies were included in the analysis. Data Synthesis: Pooled estimates showed that the impedance threshold device consistently and significantly improved return to spontaneous circulation (202/438 [46%] for impedance threshold device group vs. 159/445 [36%] for control, relative risk [RR] 1.29 [1.10‐1.51], p .002), early survival (139/428 [32%] vs. 97/433 [22%], RR 1.45 [1.16‐1.80], p .0009) and favorable neurologic outcome (39/307 [13%] vs. 18/293 [6%], RR 2.35 [1.30‐4.24], p .004) with no effect on favorable neurologic outcome in survivors (39/60 [65%] vs. 18/44 [41%]) nor an improved survival at the longest available follow up (35/428 [8.2%] vs. 24/433 [5.5%]). Conclusions: This meta-analysis of randomized controlled studies suggests that the impedance threshold device improves early outcome in patients with out-of-hospital cardiac arrest undergoing cardiopulmonary resuscitation. (Crit Care Med 2008; 36:1625‐1632)

Purpose To assess the effectiveness of acupuncture in reducing anxiety in patients having cataract surgery under topical anesthesia. Setting Vita-Salute University of Milan and IRCCS H. San Raffaele, Milan, Italy. Methods In a prospective randomized double-blind controlled trial, anxiety levels before and after cataract surgery in 3 groups (A = no acupuncture, B = true acupuncture starting 20 minutes before surgery, C = sham acupuncture starting 20 minutes before surgery) were compared using the Visual Analog Scale (VAS). Twenty-five patients scheduled for inpatient phacoemulsification were enrolled in each group. All surgeries were performed using topical anesthesia. Exclusion criteria were refusal to provide informed consent, use of drugs with sedative properties, psychiatric disease, pregnancy, knowledge of the principles of acupuncture, anatomic alterations, or cutaneous infections precluding acupuncture at the selected acupoints. Results Preoperative anxiety levels were significantly lower only in Group B (P = .001). Anxiety in Group B was significantly lower than in Group A (P = .001) and Group C (P = .037). Regarding postoperative anxiety, the mean VAS score was 39 ± 5 in Group A, 19 ± 3 in Group B, and 31 ± 4 in Group C. The difference was significant only between Group A and Group B (P = .003). Conclusion Acupuncture was effective in reducing anxiety related to cataract surgery under topical anesthesia.

Objective. To evaluate the sedative effect of acupuncture in healthy volunteers by means of the BIS monitor. Secondary end-points were the evaluation of subjective sedative sensation induced by acupuncture and possible lasting of the sedative effect post needles removal. Methods. We performed a cross-over, single-blinded study on 10 healthy volunteers to evaluate objective and subjective sedative effect of acupuncture compared to sham acupuncture. We recorded heart rate, pulse-oxymetry, BIS at baseline, during a 20-min. stimulation period, and for the following 20 minutes after needles removal. Besides, we asked volunteers to score their subjective state by VAS at baseline, after the stimulation period (20th minute) and 20 minutes after needles removal. Results. BIS values were not significantly different between true and sham acupuncture. A suggestive but not statistically significant difference was evident in VAS score, with true- better than sham acupuncture. There was no difference in the incidence of sleep during the experimental phases, nor in the incidence of insomnia or somnolence in the following 24 hours. HR and SpO2 remained always in a normal range. Conclusions. The sedative effect of true acupuncture was not different from that of sham acupuncture in healthy volunteers. We suggest that acupuncture could have a mild sedative action that can be demonstrated only treating anxious patients and not calm volunteers. In our opinion, the low potency of this technique can be an advantage allowing acupuncture safe application in a wide range of settings.

Primary pancreatic lymphoma (PPL) is a rare form of extranodal lymphoma (less than 0.5% of pancreatic tumors) originating from the pancreatic parenchyma. Histopathological examination is usually mandatory to obtain a definitive diagnosis since symptoms and radiological features are quite similar to those of other pancreatic masses. Percutaneous fine-needle aspiration (FNA) of the pancreas requires experienced cytopathologists as well as advanced immunohistochemical assays to obtain a final diagnosis on a small amount of tissue. A 46-year-old man complaining of watery diarrhea and severe weight loss (more than 20 kg) for more than 1 year was admitted to our hospital due to severe diabetic crisis. Enlarged lymph nodes (2.5 x 1 cm) were found at the right axillary stations. Abdominal ultrasound revealed the presence of a large hyperechogenic mass, mainly located at the pancreatic head. Abdominal computed tomography scan confirmed a diffuse enlargement of the head and body of the pancreas associated with lymphadenopathy along the lesser gastric curvature. Percutaneous ultrasound-guided FNA of the pancreas as well as gross biopsy of the axillary lymph nodes were unable to identify the nature of the mass. Diagnostic laparoscopy was performed: several enlarged lymph nodes along the lesser gastric curvature were revealed. Multiple biopsies of the pancreatic head were taken and lymphadenectomy along the lesser curvature and the hepatic hilus was also performed. The definitive histopathological examination of the pancreatic specimen revealed a primary low-grade non-Hodgkin B cell pancreatic lymphoma. The postoperative course was unremarkable; the patient underwent systemic chemotherapy regime for low-grade B cell Hodgkin lymphoma and he was symptom free at 9-month follow-up.

Noninvasive ventilation (NIV) is expected to become more and more common in the treatment of acute respiratory failure,[1][1] as new fields of application are explored, and evidence of its efficacy is growing. Moreover, NIV avoids some of the complications related to mechanical ventilation and, in

We read with great interest the study by Simon and colleagues about intra- and post-procedural mortality related to percutaneous dilational tracheostomy (PDT) [1]. We appreciated the huge efforts made by the authors to collect valuable data on this rare event: their findings can significantly improve daily practice in PDT performance and management in the ICU. We present three additional comments. First of all, the authors affirmed that a standard use of ultrasound neck evaluation and continuous bronchoscopy could reduce the incidence of bleeding and airway complications, respectively. However, it must be underlined that the most common intra-procedural cause of death reported in this study was pneumothorax. Thus, the complete or almost complete tracheal occlusion by dilators or the bronchoscope should be minimized to avoid air trapping. Moreover, the safest ventilatory setting while PDT is performed is unknown, and research on this topic is urgently needed. Air trapping within the lungs (a potential cause of overinflation and pneumothorax), caused by a valve effect while performing PDT, should be carefully avoided through the adoption of lower positive end-expiratory pressure, lower respiratory rate, and smaller tidal volumes [2]. Secondly, the dislocation of the tracheal cannula is a common cause of late mortality: the development of a dedicated ‘crisis’ flowchart, the immediate availability of the required equipment, and periodic personnel retraining drills [3] should be considered similarly to other protocols already validated for emergent conditions like intubation in critically ill patients [4]. Finally, the available PDT techniques are not equally safe. Some evidence exists that the single-dilator technique is safer than the others at least intra-procedurally and could be considered the first choice [5].

The aim of our study is to evaluate the lung ultrasound (LUS) reaeration score (ReS) as a predictive tool for non-invasive ventilation (NIV) efficacy in general wards for acute respiratory failure (ARF) treatment. Even if ICUs are considered the safest place to perform NIV, a shortage of intensive beds has lead to NIV application outside the ICU. With appropriate patient selection, treatment-timing choice, adequate monitoring and staff training, NIV application in general wards can allow one to safely treat patients at an early stage with better cost-effectiveness [1]. Few data assessing the right tool to evaluate NIV treatment efficacy are available.

Dear Editor,We read with great interest the reviewof Matamis and co-workers aboutdiaphragm evaluation with ultra-sounds in critically ill patients [1].We would like to add some consid-erations about three relevant issues.The authors state that duringassisted mechanical ventilation(namely pressure support ventilation,PSV), the diaphragmatic excursionmeasured with ultrasounds is theresult of the sum of patient’s effortand pressure support given by theventilator. However, since diaphrag-matic excursion is related to tidalvolumes [2, 3], compliance of respi-ratory system plays an important rolein diaphragmatic excursion. In fact, ina patient with low respiratory systemcompliance, the same pressure sup-port added to the same patient’s effortwill result in a low tidal volume,causing a minor displacement of thediaphragm. On the other side, arespiratory system with higher com-pliance will show a higher tidalvolume and a larger diaphragmaticexcursion. We agree with the authorsthat the variable that better helps toquantify the impact of patient effortin the generation of tidal volumes isthe thickening fraction (TF = thick-ness at end-inspiration–thickness atend-expiration/thickness at end-expi-ration) [4].Another crucial point is the role ofPEEP on the diaphragmatic mea-surements. The expected effect ofPEEP/CPAP both in invasive andnon-invasive ventilation is to increasefunctional residual capacity (FRC),maintaining alveolar recruitment; thecorresponding increase in lung vol-umes lowers diaphragmatic dome [5].This effect can result in a decreaseddiaphragmatic excursion, not relatedto diaphragmatic dysfunction but to acaudal displacement of diaphragmaticdome at the end of expiration.Finally, diaphragmatic excursionmeasurements with ultrasonographycan vary widely with patient’s posi-tion. Trans-diaphragmatic pressure isthe result of the difference betweenabdominal and thoracic pressures:diaphragmatic muscular force actsagainst abdominal pressure, and themagnitude of this force is higher inthe supine position than in semi-recumbent or in seated position. Thiseffect is stronger in obese patients andin patients with intra-abdominalhypertension [6]. Hence, repeatedmeasures should be taken in the sameposition to avoid pitfalls in evaluationof diaphragmatic function over timein the same patient.Diaphragmatic ultrasounds is avery promising tool for respiratoryfunction monitoring in ICU, andprotocols that take into account dia-phragmatic function may lead toimproved outcomes such as reductionof time under mechanical ventilation;we therefore congratulate the authorsfor the exhaustive description of thetechnique and its clinicalapplications.

Dear Editor, We read with great interest the report of Djibre et al. [1] on a pregnant woman with H1N1-correlated severe acute respiratory distress syndrome (ARDS) successfully treated with noninvasive ventilation (NIV). We agree that a trial of NIV can be attempted in most cases of acute respiratory failure [2], in particular when the patient is admitted in the ICU; nevertheless, in our opinion the reported case was unfit for a prolonged NIV treatment. The positive outcome was likely due to the high expertise of the authors, but generalization of their decision to avoid tracheal intubation in such critical conditions should be discouraged as too hazardous. The pregnant woman presented with severe ARDS (PaO2/FiO2 ratio \100), and NIV is commonly contraindicated in this condition [3] (above all in the absence of any contraindication to tracheal intubation). Even if the best ventilatory parameters to treat ARDS are still a matter of debate, the authors applied for 72 h a maximal FiO2/minimal PEEP strategy that is very far from standard ARDS treatment. Furthermore, when the patient worsened requiring intermittent NIV after a temporary improvement, bronchoalveolar lavage, transports to perform two CT scans, and caesarean section were performed still avoiding preventive tracheal intubation. We believe that a prudential, elective tracheal intubation, best if preceded by NIV to preoxygenate the patient [4], was indicated by the risk of acute deterioration associated with those maneuvers and by the extremely high risk of severe hypoxia in case of emergent tracheal intubation in an ARDS patient (in particular outside the ICU), aggravated by the potential difficult airway management in pregnant women. The risk of consequences for the fetus was another crucial reason to perform a preventive tracheal intubation. The authors reported that fetal monitoring was always satisfactory, and the infant was in good health; while we congratulate the authors for the successful management, we feel that the fetus was at very high (preventable) risk of permanent consequences in case of maternal sudden deterioration [5]. During a recent influenza A pandemic, pregnant women were shown to be at a relatively high risk of ARDS, and the possibility of future (or even imminent) viral pandemia with analogous characteristics exists. We strongly suggest a more prudential approach to ventilatory support in pregnant women with severe ARDS, preferring elective tracheal intubation whenever emergent intubation could have devastating consequences for the mother and the fetus and to allow a protective ventilatory strategy.

Introduction: Non-invasive ventilation is a well-established treatment for acute respiratory failure, being increasingly applied in the prehospital setting. This systematic review and meta-analysis aims to investigate whether early prehospital initiation of non-invasive ventilation reduces mortality compared to standard oxygen therapy.Methods: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception to February 7th, 2022, for studies comparing prehospital non-invasive ventilation performed by emergency medical services versus standard oxygen therapy in patients with acute respiratory failure. The primary outcome was mortality at the longest follow-up available.Results: We included ten randomized studies and two quasi-randomized studies for a total of 1485 patients. Prehospital treatment with non-invasive ventilation compared with standard oxygen therapy did not significantly reduce mortality at the longest follow-up available (107/810 [13%] vs 114/772 [15%]; RR =0.89; 95% CI, 0.70-1.13; P = 0.34; I2=24%). The endotracheal intubation rate was reduced when receiving prehospital non-invasive ventilation (38/776 [4.9%] vs 81/743 [11%]; RR =0.44; 95% CI, 0.31-0.63; P