Giovanni Borghi

Intraoperative use of tranexamic acid to reduce transfusion rate in patients undergoing radical retropubic prostatectomy: double blind, randomised, placebo controlled trial

Objectives To determine the efficacy of intraoperative treatment with low dose tranexamic acid in reducing the rate of perioperative transfusions in patients undergoing radical retropubic prostatectomy. Design Double blind, parallel group, randomised, placebo controlled trial. Setting One university hospital in Milan, Italy. Participants 200 patients older than 18 years and undergoing radical retropubic prostatectomy agreed to participate in the trial. Exclusion criteria were atrial fibrillation, coronary artery disease treated with drug eluting stent, severe chronic renal failure, congenital or acquired thrombophilia, and known or suspected allergy to tranexamic acid. Interventions Intravenous infusion of tranexamic acid or equivalent volume of placebo (saline) according to the following protocol: loading dose of 500 mg tranexamic acid 20 minutes before surgery followed by continuous infusion of tranexamic acid at 250 mg/h during surgery. Main outcome measures Primary outcome: number of patients receiving blood transfusions perioperatively. Secondary outcome: intraoperative blood loss. Six month follow-up to assess long term safety in terms of mortality and thromboembolic events. Results All patients completed treatment and none was lost to follow-up. Patients transfused were 34 (34%) in the tranexamic acid group and 55 (55%) in the control group (absolute reduction in transfusion rate 21% (95% CI 7% to 34%); relative risk of receiving transfusions for patients treated with tranexamic acid 0.62 (0.45 to 0.85); number needed to treat 5 (3 to 14); P=0.004). At follow-up, no patients died and the occurrence of thromboembolic events did not differ between the two groups. Conclusions Intraoperative treatment with low dose tranexamic acid is safe and effective in reducing the rate of perioperative blood transfusions in patients undergoing radical retropubic prostatectomy. Trial registration ClinicalTrials.gov identifier NCT00670345.

Mortality in multicenter critical care trials: An analysis of interventions with a significant effect

Objectives:We aimed to identify all treatments that affect mortality in adult critically ill patients in multicenter randomized controlled trials. We also evaluated the methodological aspects of these studies, and we surveyed clinicians’ opinion and usual practice for the selected interventions. Data Sources:MEDLINE/PubMed, Scopus, and Embase were searched. Further articles were suggested for inclusion from experts and cross-check of references. Study Selection:We selected the articles that fulfilled the following criteria: publication in a peer-reviewed journal; multicenter randomized controlled trial design; dealing with nonsurgical interventions in adult critically ill patients; and statistically significant effect in unadjusted landmark mortality. A consensus conference assessed all interventions and excluded those with lack of reproducibility, lack of generalizability, high probability of type I error, major baseline imbalances between intervention and control groups, major design flaws, contradiction by subsequent larger higher quality trials, modified intention to treat analysis, effect found only after adjustments, and lack of biological plausibility. Data Extraction:For all selected studies, we recorded the intervention and its comparator, the setting, the sample size, whether enrollment was completed or interrupted, the presence of blinding, the effect size, and the duration of follow-up. Data Synthesis:We found 15 interventions that affected mortality in 24 multicenter randomized controlled trials. Median sample size was small (199 patients) as was median centers number (10). Blinded trials enrolled significantly more patients and involved more centers. Multicenter randomized controlled trials showing harm also involved significantly more centers and more patients (p = 0.016 and p = 0.04, respectively). Five hundred fifty-five clinicians from 61 countries showed variable agreement on perceived validity of such interventions. Conclusions:We identified 15 treatments that decreased/increased mortality in critically ill patients in 24 multicenter randomized controlled trials. However, design affected trial size and larger trials were more likely to show harm. Finally, clinicians view of such trials and their translation into practice varied.

Reducing Mortality in Acute Kidney Injury Patients: Systematic Review and International Web-Based Survey

OBJECTIVE To identify all interventions that increase or reduce mortality in patients with acute kidney injury (AKI) and to establish the agreement between stated beliefs and actual practice in this setting. DESIGN AND SETTING Systematic literature review and international web-based survey. PARTICIPANTS More than 300 physicians from 62 countries. INTERVENTIONS Several databases, including MEDLINE/PubMed, were searched with no time limits (updated February 14, 2012) to identify all the drugs/techniques/strategies that fulfilled all the following criteria: (a) published in a peer-reviewed journal, (b) dealing with critically ill adult patients with or at risk for acute kidney injury, and (c) reporting a statistically significant reduction or increase in mortality. MEASUREMENTS AND MAIN RESULTS Of the 18 identified interventions, 15 reduced mortality and 3 increased mortality. Perioperative hemodynamic optimization, albumin in cirrhotic patients, terlipressin for hepatorenal syndrome type 1, human immunoglobulin, peri-angiography hemofiltration, fenoldopam, plasma exchange in multiple-myeloma-associated AKI, increased intensity of renal replacement therapy (RRT), CVVH in severely burned patients, vasopressin in septic shock, furosemide by continuous infusion, citrate in continuous RRT, N-acetylcysteine, continuous and early RRT might reduce mortality in critically ill patients with or at risk for AKI; positive fluid balance, hydroxyethyl starch and loop diuretics might increase mortality in critically ill patients with or at risk for AKI. Web-based opinion differed from consensus opinion for 30% of interventions and self-reported practice for 3 interventions. CONCLUSION The authors identified all interventions with at least 1 study suggesting a significant effect on mortality in patients with or at risk of AKI and found that there is discordance between participant stated beliefs and actual practice regarding these topics.

Dexmedetomidine vs midazolam as preanesthetic medication in children: a meta‐analysis of randomized controlled trials

The preoperative period is a stressing occurrence for most people undergoing surgery, in particular children. Approximately 50–75% of children undergoing surgery develop anxiety which is associated with distress on emergence from anesthesia and with later postoperative behavioral problems. Premedication, commonly performed with benzodiazepines, reduces preoperative anxiety, facilitates separation from parents, and promotes acceptance of mask induction. Dexmedetomidine is a highly selective α2‐agonist with sedative and analgesic properties. A meta‐analysis of all randomized controlled trials (RCTs) on dexmedetomidine versus midazolam was performed to evaluate its efficacy in improving perioperative sedation and analgesia, and in reducing postoperative agitation when used as a preanesthetic medication in children.

Volatile compared with total intravenous anaesthesia in patients undergoing high-risk cardiac surgery: a randomized multicentre study

BACKGROUND The effect of anaesthesia on postoperative outcome is unclear. Cardioprotective properties of volatile anaesthetics have been demonstrated experimentally and in haemodynamically stable patients undergoing coronary artery bypass grafting. Their effects in patients undergoing high-risk cardiac surgery have not been reported. METHODS We performed a multicentre, randomized, parallel group, controlled study among patients undergoing high-risk cardiac surgery (combined valvular and coronary surgery) in 2008-2011. One hundred subjects assigned to the treatment group received sevoflurane for anaesthesia maintenance, while 100 subjects assigned to the control group received propofol-based total i.v. anaesthesia. The primary outcome was a composite of death, prolonged intensive care unit (ICU) stay, or both. Thirty day and 1 yr follow-up, focused on mortality, was performed. RESULTS All 200 subjects completed the follow-up and were included in efficacy analyses, conducted according to the intention-to-treat principle. Death, prolonged ICU stay, or both occurred in 36 out of 100 subjects (36%) in the propofol group and in 41 out of 100 subjects (41%) in the sevoflurane group; relative risk 1.14, 95% confidence interval 0.8-1.62; P=0.5. No difference was identified in postoperative cardiac troponin release [1.1 (0.7-2) compared with 1.2 (0.6-2.4) ng ml(-1), P=0.6], 1 yr all-cause mortality [11/100 (11%) compared with 11/100 (11%), P=0.9], re-hospitalizations [20/89 (22.5%) compared with 11/89 (12.4%), P=0.075], and adverse cardiac events [10/89 (11.2%) compared with 9/89 (10.1%), P=0.8]. CONCLUSIONS There was no observed beneficial effect of sevoflurane on the composite endpoint of prolonged ICU stay, mortality, or both in patients undergoing high-risk cardiac surgery. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov: identifier NCT00821262. Eudra CT (2008-001752-43).

Intraoperative prophylactic and therapeutic non-invasive ventilation: a systematic review

Non-invasive ventilation (NIV) has been used to prevent or to treat perioperative acute respiratory failure (ARF). Intraoperative prophylactic and therapeutic use of NIV could be of interest to patients with anticipated difficulty in postoperative weaning from mechanical ventilation or to patients refusing tracheal intubation. Intraoperative NIV might also be useful when deep sedation is required, as this can cause respiratory depression. PubMed, Embase, Google Scholar, and Cochrane Library were searched for pertinent studies. Inclusion criteria were NIV use during surgery and adult patients; the exclusion criteria were NIV application only in the preoperative or postoperative periods, paediatric patients, NIV applied as negative pressure ventilation. Thirty papers including 618 patients were included for final analysis. Intraoperative therapeutic NIV to treat ARF was reported for 92 patients and in all those cases, including six Caesarean sections, surgery was completed uneventfully. Intraoperative prophylactic NIV to avoid ARF was described in 24 patients with severe respiratory limitation and in 502 healthy patients during deep sedation. Three patients could not be successfully ventilated due to upper airway obstruction, but no further complication was reported. Intraoperative NIV appears feasible, safe, and potentially useful, particularly when tracheal intubation is best avoided. However, high-quality, randomized studies are required.

Single dilator vs. guide wire dilating forceps tracheostomy: a meta-analysis of randomised trials

Single dilator technique (SDT) and guide wire dilating forceps (GWDF) are the two most commonly used techniques of percutaneous dilatational tracheostomy (PDT) in critically ill adult patients. We performed a meta‐analysis of randomised, controlled trials comparing intraoperative, mid‐term and late complications of these two techniques.

Volatile Agents in Medical and Surgical Intensive Care Units: A Meta-Analysis of Randomized Clinical Trials

OBJECTIVE To comprehensively assess published randomized peer-reviewed studies related to volatile agents used for sedation in intensive care unit (ICU) settings, with the hypothesis that volatile agents could reduce time to extubation in adult patients. DESIGN Systematic review and meta-analysis of randomized trials. SETTING Intensive care units. PARTICIPANTS Critically ill patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The BioMedCentral, PubMed, Embase, and Cochrane Central Register databases of clinical trials were searched systematically for studies on volatile agents used in the ICU setting. Articles were assessed by trained investigators, and divergences were resolved by consensus. Inclusion criteria included random allocation to treatment (volatile agents versus any intravenous comparator, with no restriction on dose or time of administration) in patients requiring mechanical ventilation in the ICU. Twelve studies with 934 patients were included in the meta-analysis. The use of halogenated agents reduced the time to extubation (standardized mean difference = -0.78 [-1.01 to -0.55] hours; p for effect<0.00001; p for heterogeneity = 0.18; I(2) = 32% in 7 studies with 503 patients). Results for time to extubation were confirmed in all subanalyses (eg, medical and surgical patients) and sensitivity analyses. No differences in length of hospital stay, ICU stay, and mortality were recorded. CONCLUSIONS In this meta-analysis of randomized trials, volatile anesthetics reduced time to extubation in medical and surgical ICU patients. The results of this study should be confirmed by large and high-quality randomized controlled studies.

Propofol and survival: A meta-analysis of randomized clinical trials

One of the most commonly used hypnotics is propofol. Several studies performed in cardiac surgery suggested an increased mortality in patients receiving a propofol‐based total intravenous anaesthesia. Furthermore, the possibility of infections and the ‘propofol syndrome’ have suggested that propofol might be dangerous. Nonetheless, propofol is widely used in different settings because of its characteristics: fast induction, rapid elimination, short duration of action, smooth recovery from anaesthesia, few adverse effects, no teratogenic effects, characteristics that have undoubtedly contributed to its popularity. The effect of propofol on survival is unknown. We decided to carry out a meta‐analysis of all randomized controlled studies ever performed on propofol vs. any comparator in any clinical setting.

Is Time to Change to Halogenated Drugs in Cardiac Surgery, What do we have to do with Propofol?

There is initial evidence, at least in cardiac surgery, that total intra-venous anesthesia (usually a propofol-based total intravenous anesthesia) is associated with an increased mortality when compared to an anesthetic plan including a halogenated anesthetics. The cardiac protective properties of halogenated agents (desflurane, isoflurane and sevoflurane) have not been confirmed in non-cardiac surgery and mixed results exist for patients admitted in postoperative intensive care units. This article summarizes the papers with the most impressive findings in favor of halogenated anesthetics, but it recognizes that, at the same time, there is no evidence based medicine against the use of propofol, highlighting the need for large randomized trials that should focus on survival.