Anaesthesia praCtice for Caesarean dElivery Snapshot Study (ACCESS): Protocol and baseline characteristics of registered centres.

BACKGROUND: Specific guidelines to manage caesarean delivery anaesthesia are lacking. A European multicentre study, ACCESS investigates caesarean delivery anaesthesia management in European centres. In order to identify ACCESS participating centres, a registration survey was created. OBJECTIVE: The aim of the current report is to describe the characteristics of ACCESS study participating centres, the rationale for the ACCESS study and the study methodology. DESIGN AND SETTING: The ACCESS study is a European multicentre cross-sectional study to describe anaesthesia management for caesarean delivery (CD) using a snapshot (2-week) design. The ACCESS registration survey gathered: contact details for National Coordinators (NC); Lead Investigators (LI) per centre; centre annual CD volume; expected no. of CD during 2-week snapshot window; centre practice information; data collection language. The ACCESS registration survey was launched July 2022 (Google Forms, Google Inc., Mountain View, CA, USA) and distributed through personal connections, national and international societies, social media networks, during Euroanaesthesia 2023, through the European Society of Anaesthesiology and Intensive Care newsletter. RESULTS: The ACCESS registration survey identified Lead Investigators for 418 centres, in 32 countries, representing an anticipated number of 15,073 CD cases over the planned 12-month study period. A median (range) of 20 (2 to 400) CD cases are anticipated per centre during the 2-week snapshot window. Most 366/418 (87.6%) centres are small, ≤2000 annual CD cases, 42 are medium 2000-5000 cases and 10 are large, ≥5000 annual CD cases. Registered centres reported in 134 (32.0%) centres that anaesthesia for caesarean delivery is performed mostly by a specialist obstetric anaesthesiologist. CONCLUSION: The ACCESS registration survey revealed variability in volume and CD practice as well as training-levels and staffing among European countries. The ACCESS study (https://www.access-study.org/) aims to generate practice data to guide CD anaesthetic management strategies.

Characteristics of children aged 2-17 years undergoing anaesthesia in Danish hospitals 2005-2015: a national observational study.

Provision of paediatric anaesthesia requires careful consideration of the child's cognitive state, unique body composition and physiology. In an observational cohort study, we describe the population characteristics and conduct of anaesthesia in children aged 2-17 years from 1 January 2005 to 31 December 2015. Children were identified from the Danish Anaesthesia Database. We recorded the following variables: age; sex; comorbidities; indications for anaesthesia; practice of anaesthesia; and complications. Results are presented for two age groups: 2-5 and 6-17 years. In total, 32,840 (61% male) children aged 2-5 years received 50,484 anaesthesia episodes and 91,418 (54% male) children aged 6-17 years received 141,082 anaesthesia episodes. The younger children, compared with the older children, were more frequently anaesthetised at a university hospital (50% vs. 36%) and for non-surgical procedures (24% vs. 8%). For both age groups, general anaesthesia was the primary choice of anaesthesia regardless of the reason for anaesthesia. For surgery, general anaesthesia using inhalational agents in addition to intravenous agents or alone was more frequently used in younger children (49% vs. 15%), whereas older children commonly received total intravenous anaesthesia (50% vs. 83%). Regional anaesthesia was infrequently utilised. Complications occurred in 3.3% of anaesthesia episodes among 2-5 year olds compared with 3.7% of anaesthesia episodes among children aged 6-17 years. In conclusion, we found younger children (aged 2-5), compared with older children (aged 6-17) were more frequently anaesthetised for non-surgical reasons, at a university hospital and using inhalational agents. Complications were rare.

The comparative efficacy and safety of sugammadex and neostigmine in reversing neuromuscular blockade in adults. A Cochrane systematic review with meta-analysis and trial sequential analysis.

We compared the efficacy and safety of sugammadex and neostigmine in reversing neuromuscular blockade in adults. Our outcomes were: recovery time from second twitch to train-of-four ratio > 0.9; recovery time from post-tetanic count 1-5 to train-of-four ratio > 0.9; and risk of composite adverse and serious adverse events. We searched for randomised clinical trials irrespective of publication status and date, blinding status, outcomes reported or language. We included 41 studies with 4206 participants. Time to reversal of neuromuscular blockade from second twitch to a train-of-four ratio > 0.9 was 2.0 min with sugammadex 2 mg.kg-1 and 12.9 min with neostigmine 0.05 mg.kg-1 , with a mean difference (MD) (95%CI)) of 10.2 (8.5-12.0) (I2  = 84%, 10 studies, n = 835, Grades of Recommendation, Assessment, Development and Evaluation (GRADE): moderate quality). Time to reversal of neuromuscular blockade from a post-tetanic count of 1-5 to a train-of-four ratio > 0.9 was 2.9 min with sugammadex 4 mg.kg-1 and 48.8 min with neostigmine 0.07 mg.kg-1 , with a MD (95%CI) of 45.8 (39.4-52.2) (I2  = 0%, 2 studies, n = 114, GRADE: low quality). There were significantly fewer composite adverse events in the sugammadex group compared with neostigmine, with a risk ratio (95%CI) of 0.60 (0.49-0.74) (I2  = 40%, 28 studies, n = 2298, number needed to treat (NNT): 8, GRADE: moderate quality). Specifically, the risk of bradycardia (RR (95%CI) 0.16 (0.07-0.34), n = 1218, NNT: 14, GRADE: moderate quality), postoperative nausea and vomiting (RR (95%CI) 0.52 (0.28-0.97), n = 389, NNT: 16, GRADE: low quality) and overall signs of postoperative residual paralysis (RR (95%CI) 0.40 (0.28-0.57), n = 1474, NNT: 13, GRADE: moderate quality) were all reduced. There was no significant difference regarding the risk of serious adverse events (RR 0.54, 95%CI 0.13-2.25, I2  = 0%, n = 959, GRADE: low quality). Sugammadex reverses neuromuscular blockade more rapidly than neostigmine and is associated with fewer adverse events.

Characteristics of children less than 2 years of age undergoing anaesthesia in Denmark 2005-2015: a national observational study.

There are few data available that describe the current anaesthetic management of children. We have analysed anaesthetic practice and peri-operative complications for children in Denmark aged less than two years. We conducted a population-based observational cohort study using the Danish Anaesthesia Database to identify children who received anaesthesia in hospital from 1 January 2005 until 31 December 2015. Data were combined with that from the Danish National Patient Registry and the Danish Civil Registration System. Age, sex, height, weight, ASA physical status, days in hospital before anaesthesia, number of anaesthetics per child, indications for anaesthesia, methods of anaesthesia, airway management and complications were all recorded. A total of 17,436 children (64% of whom were male) received 27,653 anaesthetics during the study period. In 58% of cases, the child had an ASA physical status score of 1. Thirty-seven percent had a previous anaesthetic episode. Seventy-nine percent were anaesthetised at a university hospital. The indications for anaesthesia were surgery (70%), diagnostic radiology (16%), non-surgical care (11%) and other indications (3%). General anaesthesia combining intravenous and inhalational agents was the most common approach for surgery (68%) and diagnostic radiology (47%). For non-surgical care, general anaesthesia using inhalational agents was the most common method (42%). Neuraxial blocks were used infrequently. The most common regional anaesthetic nerve block was an infraclavicular brachial plexus block (11%). Peri-operative complications occurred in 1.71% of cases. A large proportion of anaesthetics were conducted in children with comorbidities. Non-surgical indications for anaesthesia were frequent and peri-operative complications were rare.

Thromboelastography (TEG) or rotational thromboelastometry (ROTEM) to monitor haemostatic treatment in bleeding patients: a systematic review with meta-analysis and trial sequential analysis.

Coagulopathy and severe bleeding are associated with high mortality. We evaluated haemostatic treatment guided by the functional viscoelastic haemostatic assays, thromboelastography or rotational thromboelastometry in bleeding patients. We searched for randomised, controlled trials irrespective of publication status, publication date, blinding status, outcomes published or language from date of inception to 5 January 2016 in six bibliographic databases. We included 17 trials (1493 participants), most involving cardiac surgery. Thromboelastography or rotational thromboelastometry seemed to reduce overall mortality compared to any of our comparisons (3.9% vs. 7.4%, RR (95% CI) 0.52 (0.28-0.95); I2 = 0%, 8 trials, 717 participants). However, the quality of evidence is graded as low due to the high risk of bias, heterogeneity, imprecision and low event rate. Thromboelastography or rotational thromboelastometry significantly reduced the proportion of patients transfused with red blood cells (RR (95% CI) 0.86 (0.79-0.94); I2 = 0%, 10 trials, 832 participants), fresh frozen plasma (RR (95% CI) 0.57 (0.33-0.96); I2 = 86%, 10 trials, 832 participants) and platelets (RR (95% CI) 0.73 (0.60-0.88); I2 = 0%, 10 studies, 832 participants). There was no difference in proportion needing surgical re-interventions (RR (95% CI) 0.75 (0.50-1.10); I2 = 0%, 9 trials, 887 participants). Trial sequential analysis of mortality suggests that only 54% of the required information size has been reached so far. Transfusion strategies guided by thromboelastography or rotational thromboelastometry may reduce the need for blood products in patients with bleeding, but the results are mainly based on trials of elective cardiac surgery involving cardiopulmonary bypass, with low-quality evidence.

The effect of inhaled nitric oxide in acute respiratory distress syndrome in children and adults: a Cochrane Systematic Review with trial sequential analysis.

Acute respiratory distress syndrome is associated with high mortality and morbidity. Inhaled nitric oxide has been used to improve oxygenation but its role remains controversial. Our primary objective in this systematic review was to examine the effects of inhaled nitric oxide administration on mortality in adults and children with acute respiratory distress syndrome. We included all randomised, controlled trials, irrespective of date of publication, blinding status, outcomes reported or language. Our primary outcome measure was all-cause mortality. We performed several subgroup and sensitivity analyses to assess the effect of inhaled nitric oxide. There was no statistically significant effect of inhaled nitric oxide on longest follow-up mortality (inhaled nitric oxide group 250/654 deaths (38.2%) vs. control group 221/589 deaths (37.5%; relative risk (95% CI) 1.04 (0.9-1.19)). We found a significant improvement in PaO2 /FI O2 ratio at 24 h (mean difference (95% CI) 15.91 (8.25-23.56)), but not at 48 h or 72 h, while four trials indicated improved oxygenation in the inhaled nitric oxide group at 96 h (mean difference (95% CI) 14.51 (3.64-25.38)). There were no statistically significant differences in ventilator-free days, duration of mechanical ventilation, resolution of multi-organ failure, quality of life, length of stay in intensive care unit or hospital, cost-benefit analysis and methaemoglobin and nitrogen dioxide levels. There was an increased risk of renal impairment (risk ratio (95% CI) 1.59 (1.17-2.16)) with inhaled nitric oxide. In conclusion, there is insufficient evidence to support inhaled nitric oxide in any category of critically ill patients with acute respiratory distress syndrome despite a transient improvement in oxygenation, since mortality is not reduced and it may induce renal impairment.

Patient-controlled analgesia with remifentanil vs. alternative parenteral methods for pain management in labour: a Cochrane systematic review.

We aimed to assess the effectiveness of remifentanil used as intravenous patient-controlled analgesia for the pain of labour. We performed a systematic literature search in December 2015 (updated in December 2016). We included randomised, controlled and cluster-randomised trials of women in labour with planned vaginal delivery receiving patient-controlled remifentanil compared principally with other parenteral and patient-controlled opioids, epidural analgesia and continuous remifentanil infusion or placebo. The primary outcomes were patient satisfaction with pain relief and the occurrence of adverse events for mothers and newborns. We assessed risk of bias for each included study and applied the GRADE approach for the quality of evidence. We included total zero event trials, using a constant continuity correction of 0.01 and a random-effect meta-analysis. Twenty studies were included in the qualitative analysis; within these, 3713 participants were randomised and 3569 analysed. Most of our pre-specified outcomes were not studied in the included trials. However, we found evidence that women using patient-controlled remifentanil were more satisfied with pain relief than women receiving parenteral opioids (four trials, 216 patients, very low quality evidence) with a standardised mean difference ([SMD] 95%CI) of 2.11 (0.72-3.49), but were less satisfied than women receiving epidural analgesia (seven trials, 2135 patients, very low quality evidence), -0.22 (-0.40 to -0.04). Data on adverse events were sparse. However, the relative risk (95%CI) for maternal respiratory depression for patient-controlled remifentanil compared with epidural analgesia (three trials, 687 patients, low-quality evidence) was 0.91 (0.51-1.62). Compared with continuous intravenous infusion of remifentanil (two trials, 135 patients, low-quality evidence) no conclusion could be reached as all study arms showed zero events. The relative risk (95%CI) of Apgar scores less than 7 at 5 min after birth compared with epidural analgesia (five trials, 1322 participants, low-quality evidence) was 1.26 (0.62-2.57).

Prediction of difficult mask ventilation using a systematic assessment of risk factors vs. existing practice - a cluster randomised clinical trial in 94,006 patients.

We compared implementation of systematic airway assessment with existing practice of airway assessment on prediction of difficult mask ventilation. Twenty-six departments were cluster-randomised to assess eleven risk factors for difficult airway management (intervention) or to continue with their existing airway assessment (control). In both groups, patients predicted as a difficult mask ventilation and/or difficult intubation were registered in the Danish Anaesthesia Database, with a notational summary of airway management. The trial's primary outcome was the respective incidence of unpredicted difficult and easy mask ventilation in the two groups. Among 94,006 patients undergoing mask ventilation, the incidence of unpredicted difficult mask ventilation in the intervention group was 0.91% and 0.88% in the control group; (OR) 0.98 (95% CI 0.66-1.44), p = 0.90. The incidence of patients predicted difficult to mask ventilate, but in fact found to be easy ('falsely predicted difficult') was 0.64% vs. 0.35% (intervention vs. control); OR 1.56 (1.01-2.42), p = 0.045. In the intervention group, 86.3% of all difficult mask ventilations were not predicted, compared with a higher proportion 91.2% in the control group, OR 0.61 (0.41-0.91), p = 0.016. The systematic intervention did not alter the overall incidence of unpredicted difficult mask ventilations, but of the patients who were found to be difficult to mask ventilate, the proportion predicted was higher in the intervention group than in the control group. However, this was at a 'cost' of increasing the number of mask ventilations falsely predicted to be difficult.

Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis.

BACKGROUND: Improvement of postoperative pain and other perioperative outcomes remain a significant challenge and a matter of debate among perioperative clinicians. This systematic review aims to evaluate the effects of perioperative i.v. lidocaine infusion on postoperative pain and recovery in patients undergoing various surgical procedures. METHODS: CENTRAL, MEDLINE, EMBASE, and CINAHL databases and ClinicalTrials.gov, and congress proceedings were searched for randomized controlled trials until May 2014, that compared patients who did or did not receive continuous perioperative i.v. lidocaine infusion. RESULTS: Forty-five trials (2802 participants) were included. Meta-analysis suggested that lidocaine reduced postoperative pain (visual analogue scale, 0 to 10 cm) at 1-4 h (MD -0.84, 95% CI -1.10 to -0.59) and at 24 h (MD -0.34, 95% CI -0.57 to -0.11) after surgery, but not at 48 h (MD -0.22, 95% CI -0.47 to 0.03). Subgroup analysis and trial sequential analysis suggested pain reduction for patients undergoing laparoscopic abdominal surgery or open abdominal surgery, but not for patients undergoing other surgeries. There was limited evidence of positive effects of lidocaine on postoperative gastrointestinal recovery, opioid requirements, postoperative nausea and vomiting, and length of hospital stay. There were limited data available on the effect of systemic lidocaine on adverse effects or surgical complications. Quality of evidence was limited as a result of inconsistency (heterogeneity) and indirectness (small studies). CONCLUSIONS: There is limited evidence suggesting that i.v. lidocaine may be a useful adjuvant during general anaesthesia because of its beneficial impact on several outcomes after surgery.

Effects of using the simplified airway risk index vs usual airway assessment on unanticipated difficult tracheal intubation - a cluster randomized trial with 64,273 participants.

BACKGROUND: Unanticipated difficult intubation remains a challenge in anaesthesia. The Simplified Airway Risk Index (SARI) is a multivariable risk model consisting of seven independent risk factors for difficult intubation. Our aim was to compare preoperative airway assessment based on the SARI with usual airway assessment. METHODS: From 01.10.2012 to 31.12.2013, 28 departments were cluster-randomized to apply the SARI model or usual airway assessment. The SARI group implemented the SARI model. The Non-SARI group continued usual airway assessment, thus reflecting a group of anaesthetists' heterogeneous individual airway assessments. Preoperative prediction of difficult intubation and actual intubation difficulties were registered in the Danish Anaesthesia Database for both groups. Patients who were preoperatively scheduled for intubation by advanced techniques (e.g. video laryngoscopy; flexible optic scope) were excluded from the primary analysis. Primary outcomes were the proportions of unanticipated difficult and unanticipated easy intubation. RESULTS: A total of 26 departments (15 SARI and 11 Non-SARI) and 64 273 participants were included. In the primary analyses 29 209 SARI and 30 305 Non-SARI participants were included.In SARI departments 2.4% (696) of the participants had an unanticipated difficult intubation vs 2.4% (723) in Non-SARI departments. Odds ratio (OR) adjusted for design variables was 1.03 (95% CI: 0.77-1.38). The proportion of unanticipated easy intubation was 1.42% (415) in SARI departments vs 1.00% (302) in Non-SARI departments. Adjusted OR was 1.26 (0.68-2.34). CONCLUSIONS: Using the SARI compared with usual airway assessment we detected no statistical significant changes in unanticipated difficult- or easy intubations. CLINICAL TRIAL REGISTRATION: NCT01718561.

Comparing efficacy and safety of fibrinogen concentrate to cryoprecipitate in bleeding patients: a systematic review.

BACKGROUND: Bleeding is associated with the depletion of fibrinogen, thus increasing the risk of coagulopathy, further bleeding and transfusion requirements. Both fibrinogen concentrate and cryoprecipitate replenish low plasma fibrinogen levels. This systematic review aims to identify and evaluate evidence of efficacy and safety of fibrinogen concentrate and cryoprecipitate in bleeding patients. METHOD: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, EMBASE up to 2nd of March 2015 were among the electronic search strategies of randomized controlled trials and non-randomized studies with meta-analysis employed. Studies for inclusion required bleeding patients being treated with either fibrinogen concentrate or cryoprecipitate. Mortality was the primary endpoint. Secondary outcomes included bleeding, coagulopathy, transfusion requirements and clinical complications related to the intervention. PRISMA methodology, a data-extraction form and the Cochrane risk of bias tool were all employed. RESULTS: Four studies were eligible for inclusion in this systematic review; one randomized controlled trial (RCT) consisting of 66 patients and three observational studies involving 218 patients in total. No mortality was reported in the published papers. There were no differences in fibrinogen-level increase, bleeding, RBC transfusions or thromboembolic complications. The RCT showed a possible increased functional improvement of haemostasis after cryoprecipitate therapy compared to fibrinogen concentrate. CONCLUSION: The available evidence directly comparing fibrinogen concentrate to cryoprecipitate is sparse and with high risk of bias. Recommendation of one product over the other for fibrinogen substitution in the bleeding patient with acquired hypofibrinogenaemia is currently not possible. Future research should guide us towards evidence-based decisions of product superiority.

Pre-emptive treatment with fibrinogen concentrate for postpartum haemorrhage: randomized controlled trial.

BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.

Diagnostic accuracy of anaesthesiologists' prediction of difficult airway management in daily clinical practice: a cohort study of 188 064 patients registered in the Danish Anaesthesia Database.

Both the American Society of Anesthesiologists and the UK NAP4 project recommend that an unspecified pre-operative airway assessment be made. However, the choice of assessment is ultimately at the discretion of the individual anaesthesiologist. We retrieved a cohort of 188 064 cases from the Danish Anaesthesia Database, and investigated the diagnostic accuracy of the anaesthesiologists' predictions of difficult tracheal intubation and difficult mask ventilation. Of 3391 difficult intubations, 3154 (93%) were unanticipated. When difficult intubation was anticipated, 229 of 929 (25%) had an actual difficult intubation. Likewise, difficult mask ventilation was unanticipated in 808 of 857 (94%) cases, and when anticipated (218 cases), difficult mask ventilation actually occurred in 49 (22%) cases. We present a previously unpublished estimate of the accuracy of anaesthesiologists' prediction of airway management difficulties in daily routine practice. Prediction of airway difficulties remains a challenging task, and our results underline the importance of being constantly prepared for unexpected difficulties.

Fibrinogen concentrate for bleeding--a systematic review.

Fibrinogen concentrate as part of treatment protocols increasingly draws attention. Fibrinogen substitution in cases of hypofibrinogenaemia has the potential to reduce bleeding, transfusion requirement and subsequently reduce morbidity and mortality. A systematic search for randomised controlled trials (RCTs) and non-randomised studies investigating fibrinogen concentrate in bleeding patients was conducted up to November 2013. We included 30 studies of 3480 identified (7 RCTs and 23 non-randomised). Seven RCTs included a total of 268 patients (165 adults and 103 paediatric), and all were determined to be of high risk of bias and none reported a significant effect on mortality. Two RCTs found a significant reduction in bleeding and five RCTs found a significant reduction in transfusion requirements. The 23 non-randomised studies included a total of 2825 patients, but only 11 of 23 studies included a control group. Three out of 11 found a reduction in transfusion requirements while mortality was reduced in two and bleeding in one. In the available RCTs, which all have substantial shortcomings, we found a significant reduction in bleeding and transfusions requirements. However, data on mortality were lacking. Weak evidence from RCTs supports the use of fibrinogen concentrate in bleeding patients, primarily in elective cardiac surgery, but a general use of fibrinogen across all settings is only supported by non-randomised studies with serious methodological shortcomings. It seems pre-mature to conclude whether fibrinogen concentrate has a routine role in the management of bleeding and coagulopathic patients. More RCTs are urgently warranted.

Indoor aerosols: from personal exposure to risk assessment.

Motivated by growing considerations of the scale, severity, and risks associated with human exposure to indoor particulate matter, this work reviewed existing literature to: (i) identify state-of-the-art experimental techniques used for personal exposure assessment; (ii) compare exposure levels reported for domestic/school settings in different countries (excluding exposure to environmental tobacco smoke and particulate matter from biomass cooking in developing countries); (iii) assess the contribution of outdoor background vs indoor sources to personal exposure; and (iv) examine scientific understanding of the risks posed by personal exposure to indoor aerosols. Limited studies assessing integrated daily residential exposure to just one particle size fraction, ultrafine particles, show that the contribution of indoor sources ranged from 19% to 76%. This indicates a strong dependence on resident activities, source events and site specificity, and highlights the importance of indoor sources for total personal exposure. Further, it was assessed that 10-30% of the total burden of disease from particulate matter exposure was due to indoor-generated particles, signifying that indoor environments are likely to be a dominant environmental factor affecting human health. However, due to challenges associated with conducting epidemiological assessments, the role of indoor-generated particles has not been fully acknowledged, and improved exposure/risk assessment methods are still needed, together with a serious focus on exposure control.

Transfusion in critically ill children: an ongoing dilemma.

Transfusion of blood products is a cornerstone in managing many critically ill children. Major improvements in blood product safety have not diminished the need for caution in transfusion practice. In this review, we aim to discuss the interplay between benefits and potential adverse effects of transfusion in critically ill children by including 65 papers, which were evaluated based on previously agreed selection criteria. Current practice on transfusing critically ill children is mainly founded on the basis of adult studies, common practices with cut-off values, and expert opinions, rather than evidence-based medicine. Paediatric patients have explicit physiological challenges and requirements to be addressed. Critically ill children often suffer from anaemia, have substantial iatrogenic blood loss with subsequent transfusions, and are at a higher risk of complications, often due to human errors. Transfusion in children is associated with increased morbidity. A restrictive transfusion strategy is not associated with increased morbidity. Thus, transfusion in paediatrics should be considered a high-risk treatment and requires individual clinical assessment. Current level of evidence support the notion that in most stable cases, despite high severity of illness (cyanotic children and neonates excluded), a restrictive haemoglobin threshold of 70 g/l (4.3 mmol/l) is no more harmful than to transfuse at a liberal trigger, e.g. haemoglobin 95 g/l (5.9 mmol/l). Thus, balanced against potential benefits and often its necessity, a restrictive approach may be appropriate due to the associated risks of transfusion.

Pulmonary and cardiovascular responses of rats to inhalation of a commercial antimicrobial spray containing titanium dioxide nanoparticles.

Our laboratory has previously demonstrated that application of an antimicrobial spray product containing titanium dioxide (TiO(2)) generates an aerosol of titanium dioxide in the breathing zone of the applicator. The present report describes the design of an automated spray system and the characterization of the aerosol delivered to a whole body inhalation chamber. This system produced stable airborne levels of TiO(2) particles with a median count size diameter of 110 nm. Rats were exposed to 314 mg/m(3) min (low dose), 826 mg/m(3) min (medium dose), and 3638 mg/m(3) min (high dose) of TiO(2) under the following conditions: 2.62 mg/m(3) for 2 h, 1.72 mg/m(3) 4 h/day for 2 days, and 3.79 mg/m(3) 4 h/day for 4 days, respectively. Pulmonary (breathing rate, specific airway resistance, inflammation, and lung damage) and cardiovascular (the responsiveness of the tail artery to constrictor or dilatory agents) endpoints were monitored 24 h post-exposure. No significant pulmonary or cardiovascular changes were noted at low and middle dose levels. However, the high dose caused significant increases in breathing rate, pulmonary inflammation, and lung cell injury. Results suggest that occasional consumer use of this antimicrobial spray product should not be a hazard. However, extended exposure of workers routinely applying this product to surfaces should be avoided. During application, care should be taken to minimize exposure by working under well ventilated conditions and by employing respiratory protection as needed. It would be prudent to avoid exposure to children or those with pre-existing respiratory disease.