Arash Afshari

Inhaled nitric oxide for acute respiratory distress syndrome and acute lung injury in adults and children: a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Acute hypoxemic respiratory failure, defined as acute lung injury and acute respiratory distress syndrome, are critical conditions associated with frequent mortality and morbidity in all ages. Inhaled nitric oxide (iNO) has been used to improve oxygenation, but its role remains controversial. We performed a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials (RCTs). We searched CENTRAL, Medline, Embase, International Web of Science, LILACS, the Chinese Biomedical Literature Database, and CINHAL (up to January 31, 2010). Additionally, we hand-searched reference lists, contacted authors and experts, and searched registers of ongoing trials. Two reviewers independently selected all parallel group RCTs comparing iNO with placebo or no intervention and extracted data related to study methods, interventions, outcomes, bias risk, and adverse events. All trials, irrespective of blinding or language status were included. Retrieved trials were evaluated with Cochrane methodology. Disagreements were resolved by discussion. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effect of iNO in adults and children and on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components. We assessed the risk of random error by applying trial sequential analysis. RESULTS: We included 14 RCTs with a total of 1303 participants; 10 of these trials had a high risk of bias. iNO showed no statistically significant effect on overall mortality (40.2%versus 38.6%) (relative risks [RR] 1.06, 95% confidence interval [CI] 0.93 to 1.22; I2 = 0) and in several subgroup and sensitivity analyses, indicating robust results. Limited data demonstrated a statistically insignificant effect of iNO on duration of ventilation, ventilator-free days, and length of stay in the intensive care unit and hospital. We found a statistically significant but transient improvement in oxygenation in the first 24 hours, expressed as the ratio of PO2 to fraction of inspired oxygen (mean difference [MD] 15.91, 95% CI 8.25 to 23.56; I2 = 25%). However, iNO appears to increase the risk of renal impairment among adults (RR 1.59, 95% CI 1.17 to 2.16; I2 = 0) but not the risk of bleeding or methemoglobin or nitrogen dioxide formation. CONCLUSION: iNO cannot be recommended for patients with acute hypoxemic respiratory failure. iNO results in a transient improvement in oxygenation but does not reduce mortality and may be harmful.

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.

Bench-to-bedside review: Rapid molecular diagnostics for bloodstream infection - a new frontier?

Among critically ill patients, the diagnosis of bloodstream infection poses a major challenge. Current standard bacterial identification based on blood culture platforms is intrinsically time-consuming and slow. The continuous evolvement of molecular techniques has the potential of providing a faster, more sensitive and direct identification of causative pathogens without prior need for cultivation. This may ultimately impact clinical decision-making and antimicrobial treatment. This review summarises the currently available technologies, their strengths and limitations and the obstacles that have to be overcome in order to develop a satisfactory bedside point-of-care diagnostic tool for detection of bloodstream infection.

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 FIB-PPH trial: fibrinogen concentrate as initial treatment for postpartum haemorrhage: study protocol for a randomised controlled trial

BackgroundPostpartum haemorrhage (PPH) remains a leading cause of maternal mortality worldwide. In Denmark 2% of parturients receive blood transfusion. During the course of bleeding fibrinogen (coagulation factor I) may be depleted and fall to critically low levels, impairing haemostasis and thus worsening the ongoing bleeding. A plasma level of fibrinogen below 2 g/L in the early phase of postpartum haemorrhage is associated with subsequent development of severe haemorrhage. Use of fibrinogen concentrate allows high-dose substitution without the need for blood type crossmatch. So far no publications of randomised controlled trials involving acutely bleeding patients in the obstetrical setting have been published. This trial aims to investigate if early treatment with fibrinogen concentrate reduces the need for blood transfusion in women suffering severe PPH.Methods/DesignIn this randomised placebo-controlled double-blind multicentre trial, parturients with primary PPH are eligible following vaginal delivery in case of: manual removal of placenta (blood loss ≥ 500 ml) or manual exploration of the uterus after the birth of placenta (blood loss ≥ 1000 ml). Caesarean sections are also eligible in case of perioperative blood loss ≥ 1000 ml. The exclusion criteria are known inherited haemostatic deficiencies, prepartum treatment with antithrombotics, pre-pregnancy weight <45 kg or refusal to receive blood transfusion. Following informed consent, patients are randomly allocated to either early treatment with 2 g fibrinogen concentrate or 100 ml isotonic saline (placebo). Haemostatic monitoring with standard laboratory coagulation tests and thromboelastography (TEG, functional fibrinogen and Rapid TEG) is performed during the initial 24 hours.Primary outcome is the need for blood transfusion. To investigate a 33% reduction in the need for blood transfusion, a total of 245 patients will be included. Four university-affiliated public tertiary care hospitals will include patients during a two-year period. Adverse events including thrombosis are assessed in accordance with International Conference on Harmonisation (ICH) good clinical practice (GCP).DiscussionA widespread belief in the benefits of early fibrinogen substitution in cases of PPH has led to increased off-label use. The FIB-PPH trial is investigator-initiated and aims to provide an evidence-based platform for the recommendations of the early use of fibrinogen concentrate in PPH.Trial registrationClincialTrials.gov NCT01359878.

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.

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.

Year in review 2011: Critical Care – infection

In 2009 Critical Care provided important and clinically relevant research data for management and prevention of infections in critically ill patients. The present review summarises the results of these observational studies and clinical trials and discusses them in the context of the current relevant scientific and clinical background. In particular, we discuss recent epidemiologic data on nosocomial infections in intensive care units, present new approaches to prevention of ventilator-associated pneumonia, describe recent advances in biomarker-guided antibiotic stewardship and attempt to briefly summarise specific challenges related to the management of infections caused by multidrug-resistant microorganisms and influenza A (H1N1).

When may systematic reviews and meta-analyses be considered reliable?

In a systematic review in this issue of the European Journal of Anaesthesiology, Stevanovic et al. compare the event rate of upper airway adverse events and recovery after desflurane in comparison with other volatile anaesthetics and propofol in patients undergoing general surgery with a laryngeal mask airway (LMA). The authors found desflurane comparable with other agents with regard to upper airway reactions, but desflurane appeared to offer a significantly faster emergence from general anaesthesia. Furthermore, the authors advocate the need for large multicentre trials because large inter-study variations were detected. In light of such uncertainty, does inclusion of less than 600 patients in most of the primary and secondary outcome statistics across 13 trials in this systematic review justify drawing firm conclusions or even partially answer the clinical questions of interest? To answer the above questions, one should look beyond the numbers and reflect on some fundamental issues. Systematic reviews and meta-analyses serve the important purpose of identifying potential benefits or harms of an intervention and ideally provide the answers in a rapid and reliable manner. They are often the cornerstone of clinical practice guidelines and may serve as a justification for funding of further trials.

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

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.