Halogenated anesthetics vs intravenous hypnotics for short and long term sedation in the intensive care unit: A meta-analysis.

OBJECTIVE: To comprehensively assess peer-reviewed studies using volatile (VA) or intravenous (i/v) anesthetics for sedation in intensive care units (ICUs), with the hypothesis that the type of sedation may have an impact on survival and other clinically relevant outcomes. DESIGN: Systematic review and meta-analysis of randomized and non-randomized trials. SETTING: ICUs. PARTICIPANTS: Critically ill and postoperative patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Studies comparing VA versus i/v anesthetics used in the ICU settings were independently systematically searched. Finally, 15 studies (1520 patients of predominantly surgical profile needed VA sedation for less than 96h) were included. VA had no impact on all-cause mortality (very low quality of evidence, Odds Ratio=0.82 [0.60-1.12], p=0.20). However, VA were associated with a reduction in duration of mechanical ventilation (p=0.03) and increase in ventilator-free days (p<0.001). VA also reduced postoperative levels of cardiac troponin (24h), time to extubation (p<0.001) and awakening (p=0.04). CONCLUSIONS: In this meta-analysis, volatile sedation vs propofol caused the increase in ventilator-free days, the reduction in the duration of mechanical ventilation, time to extubation and the troponin release in medical or surgical ICU patients, while in surgical ICU patients the time to awakening was shortened.

A double-blind randomised feasibility trial of angiotensin-2 in cardiac surgery.

Acute kidney injury is common after cardiac surgery. Vasoplegic hypotension may contribute to kidney injury, and different vasopressors may have variable effects on kidney function. We conducted a double-blind, randomised feasibility trial comparing peri-operative angiotensin-2 with noradrenaline. We randomly allocated 60 patients at two centres to a blinded equipotent angiotensin-2 or noradrenaline infusion intra-operatively and for up to 48 h postoperatively, titrated to mean arterial pressure of 70-80 mmHg. Primary feasibility outcomes included consent rate, protocol adherence, infusion duration, mean arterial pressure maintenance in the target range and major adverse outcomes. Secondary outcomes included kidney injury rate. The consent rate was 47%. Protocol adherence was 100% in the angiotensin-2 group and 94% in the noradrenaline group. Study drug duration was median (IQR [range]) 217 (160-270 [30-315]) vs. 185 (135-301 [0-480]) min (p = 0.78) min intra-operatively, and 5 (0-16 [0-48]) vs. 14.5 (4.8-29 [0-48]) hours (p = 0.075) postoperatively for angiotensin-2 and noradrenaline, respectively. The mean arterial pressure target was achieved postoperatively in 25 of 28 (89%) of the angiotensin-2 group and 27 of 32 (84%) of the noradrenaline group. One participant had a stroke, one required extracorporeal support and three required renal replacement therapy, all in the noradrenaline group (p = 0.99, p = 0.99 and p = 0.1). Acute kidney injury occurred in 7 of 28 in the angiotensin-2 group vs. 12 of 32 patients in the noradrenaline group (p = 0.31). This pilot study suggests that a trial comparing angiotensin-2 with noradrenaline is feasible. Its findings justify further investigations of angiotensin-2 in cardiac surgery.

Awake pronation with helmet continuous positive airway pressure for COVID-19 acute respiratory distress syndrome patients outside the ICU: A case series.

OBJECTIVE: Continuous positive airway pressure (CPAP) is an important therapeutic tool in COVID-19 acute respiratory distress syndrome (ARDS) since it improves oxygenation, reduces respiratory rate and can prevent intubation and intensive care unit (ICU) admission. CPAP during pronation has seldom been described and never during sedation. DESIGN: Case series. SETTING: High dependency unit of San Carlo University Hospital (Potenza, Italy). PATIENTS: Eleven consecutive patients with COVID-19 ARDS. INTERVENTION: Helmet CPAP in prone position after failing a CPAP trial in the supine position. MAIN VARIABLE OF INTEREST: Data collection at baseline and then after 24, 48 and 72h of pronation. We measured PaO2/FIO2, pH, lactate, PaCO2, SpO2, respiratory rate and the status of the patients at 28-day follow up. RESULTS: Patients were treated with helmet CPAP for a mean±SD of 7±2.7 days. Prone positioning was feasible in all patients, but in 7 of them dexmedetomidine improved comfort. PaO2/FIO2 improved from 107.5±20.8 before starting pronation to 244.4±106.2 after 72h (p<.001). We also observed a significantly increase in Sp02 from 90.6±2.3 to 96±3.1 (p<.001) and a decrease in respiratory rate from 27.6±4.3 to 20.1±4.7 (p=.004). No difference was observed in PaCO2 or pH. At 28 days two patients died after ICU admission, one was discharged in the main ward after ICU admission and eight were discharged home after being successfully managed outside the ICU. CONCLUSIONS: Helmet CPAP during pronation was feasible and safe in COVID-19 ARDS managed outside the ICU and sedation with dexmedetomidine safely improved comfort. We recorded an increase in PaO2/FIO2, SpO2 and a reduction in respiratory rate.

Awake pronation with helmet continuous positive airway pressure for COVID-19 acute respiratory distress syndrome patients outside the ICU: A case series.

OBJECTIVE: Continuous positive airway pressure (CPAP) is an important therapeutic tool in COVID-19 acute respiratory distress syndrome (ARDS) since it improves oxygenation, reduces respiratory rate and can prevent intubation and intensive care unit (ICU) admission. CPAP during pronation has seldom been described and never during sedation. DESIGN: Case series. SETTING: High dependency unit of San Carlo University Hospital (Potenza, Italy). PATIENTS: Eleven consecutive patients with COVID-19 ARDS. INTERVENTION: Helmet CPAP in prone position after failing a CPAP trial in the supine position. MAIN VARIABLE OF INTEREST: Data collection at baseline and then after 24, 48 and 72h of pronation. We measured PaO2/FIO2, pH, lactate, PaCO2, SpO2, respiratory rate and the status of the patients at 28-day follow up. RESULTS: Patients were treated with helmet CPAP for a mean±SD of 7±2.7 days. Prone positioning was feasible in all patients, but in 7 of them dexmedetomidine improved comfort. PaO2/FIO2 improved from 107.5±20.8 before starting pronation to 244.4±106.2 after 72h (p<.001). We also observed a significantly increase in Sp02 from 90.6±2.3 to 96±3.1 (p<.001) and a decrease in respiratory rate from 27.6±4.3 to 20.1±4.7 (p=.004). No difference was observed in PaCO2 or pH. At 28 days two patients died after ICU admission, one was discharged in the main ward after ICU admission and eight were discharged home after being successfully managed outside the ICU. CONCLUSIONS: Helmet CPAP during pronation was feasible and safe in COVID-19 ARDS managed outside the ICU and sedation with dexmedetomidine safely improved comfort. We recorded an increase in PaO2/FIO2, SpO2 and a reduction in respiratory rate.

The Fragility Index in peri-operative randomised trials that reported significant mortality effects in adults.

More than one million peri-operative patients die each year. Thus, small improvements in peri-operative care may save thousands of lives. However, clinicians need confidence in the robustness of trial findings. The Fragility Index may complement frequentist analysis and provide quantitative assessment of robustness. We searched MEDLINE for peri-operative critical care randomised controlled trials that reported a statistically significant difference in mortality. We identified 46 trials with 37,347 participants. The median (IQR [range]) Fragility Index was 2 (1-3 [0-49]). Eleven trials had a Fragility Index of zero (changing from the Chi-square test to Fisher's exact test removed significance) and seven trials had a Fragility Index of 1. Only 23/46 trials had a Fragility Index greater than the number of patients lost to follow-up. There was a strong positive correlation between the Fragility Index and: the number of participants, R2  = 0.97, p < 0.0001; the number of centres that recruited participants, R2  = 0.96, p < 0.0001; the number of nations that recruited participants, R2  = 0.93, p < 0.0001; and the number of deaths, R2  = 0.97, p < 0.0001. As measured by the Fragility Index, the effect of peri-operative interventions on mortality in individual randomised controlled trials are not robust.

The impact of non-blinding in critical care medicine trials.

PURPOSE: It is uncertain whether, in critical care medicine, non-blinded trials are associated with a bias toward a different effect size. The aim of our study was to assess if conducting non-blinded/open label studies leads to greater effect size than blinded studies, and to provide an estimate of the weight of this difference. MATERIALS AND METHODS: We systematically searched all papers published in peer-reviewed journals between January 2000 and December 2015, dealing with non surgical interventions in critically ill adults and reporting a statistically significant difference in mortality. We assessed the number needed to treat (NNT) of each trial to estimate the treatment effect size and we divided studies into non-blinded, single-blinded and double-blinded. We searched for correlation between the treatment effect size and blinding, and adjusted for the other trial variables. RESULTS: We identified 119 critically ill randomized controlled trials. Of these, 69 studies were non-blinded and 50 were blinded. The median NNT in non-blinded studies was 5 [IQR 4-7] while it was 7 [IQR 5-7] in the blinded studies (p < .001). CONCLUSIONS: The NNT for blinded studies is 40% higher than for unblinded studies. This should be taken into account when planning and interpreting the findings of non-blinded studies performed in critically ill settings.

Early mobilization programme improves functional capacity after major abdominal cancer surgery: a randomized controlled trial.

Background: Major abdominal oncology surgery is associated with substantial postoperative loss of functional capacity, and exercise may be an effective intervention to improve outcomes. The aim of this study was to assess efficacy, feasibility and safety of a supervised postoperative exercise programme. Methods: We performed a single-blind, parallel-arm, randomized trial in patients who underwent major abdominal oncology surgery in a tertiary university hospital. Patients were randomized to an early mobilization postoperative programme based on supervised aerobic exercise, resistance and flexibility training or to standard rehabilitation care. The primary outcome was inability to walk without human assistance at postoperative day 5 or hospital discharge. Results: A total of 108 patients were enrolled, 54 into the early mobilization programme group and 54 into the standard rehabilitation care group. The incidence of the primary outcome was nine (16.7%) and 21 (38.9%), respectively (P=0.01), with an absolute risk reduction of 22.2% [95% confidence interval (CI) 5.9-38.6] and a number needed to treat of 5 (95% CI 3-17). All patients in the intervention group were able to follow at least partially the exercise programme, although the performance among them was rather heterogeneous. There were no differences between groups regarding clinical outcomes or complications related to the exercises. Conclusions: An early postoperative mobilization programme based on supervised exercises seems to be safe and feasible and improves functional capacity in patients undergoing major elective abdominal oncology surgery. However, its impact on clinical outcomes is still unclear. Clinical trial registration: NCT01693172.

Controlling catheter-related bloodstream infections through a multi-centre educational programme for intensive care units.

BACKGROUND: Bloodstream infections (BSIs) associated with insertion and maintenance of central venous catheters (CRBSIs) are the most frequent causes of healthcare-associated infections in intensive care units (ICUs). They are responsible for increased length of hospital stay and additional healthcare costs. AIM: To investigate whether an educational programme aimed at healthcare workers resulted in a significant change in the level and trend of infections. METHODS: The research was conducted in five Italian ICUs from July 2012 to August 2014. Surveillance and educational interventions to control infections were applied. Compliance with hand hygiene procedures was assessed via relative risk and 95% confidence interval. Interrupted time-series analysis was used to investigate the change in level and trend of infection during the intervention. FINDINGS: Compliance with hand hygiene procedures improved during the intervention for all staff groups, but physicians showed the lowest compliance rates (nurses from 52.4% to 92.1%; nurse aides from 71.0% to 92%; physicians from 71.0% to 92%; P < 0.001). Significant reductions of 21-55% in CRBSI were observed during the intervention. Small improvements in the monthly infection trend were also observed, but these were not statistically significant. CONCLUSION: An educational programme focusing on general good infection control practice, rather than CVC care bundles, led to a decreased CRBSI rate, even if the improvement was not sustained over time. Continuous performance feedback should be provided to promote long-term adherence to guidelines among all health workers.

Predicting the Need for Intra-operative Large Volume Blood Transfusions During Thoraco-abdominal Aortic Aneurysm Repair.

OBJECTIVE: Thoraco-abdominal aortic aneurysm (TAAA) repair is a complex procedure performed in patients at high cardiovascular risk. High volume intra-operative bleeding is often recorded, and the amount of intra-operative blood product transfusion is associated with relevant morbidity and mortality. The aim of the study was to identify pre-operative predictors of intra-operative large volume blood transfusions (LVBT) to stratify patients pre-operatively. METHODS: This was a retrospective analysis of prospectively collected data of all patients who underwent open TAAA surgery at San Raffaele Scientific Institute from January 2009 to December 2015. Intra-operative red blood cell (RBC) transfusions were administered to maintain a hematocrit of at least 30%. A LVBT was defined as a transfusion of at least four RBC units, corresponding to 1000 mL. RESULTS: The study population included 428 patients: 260 (61%) received fewer than 4 RBC units, and 168 (39%) were transfused with at least 4 RBC units. In patients who underwent LVBT, higher mortality was observed after surgery (p=.003), longer intensive care unit admission (p=.004), and longer mechanical ventilation compared with less transfused patients (p=.0002). The patients who received fewer units were administered a higher dose of heparin during the surgical operation compared with patients of the LVBT group: 3400±1100 vs. 2900±1300 IU (international units) (p=.0004). Pre-operative chronic renal failure (OR 1.8), the pre-operative haemoglobin value (OR 0.8), and the need for urgent or emergent surgery (OR 3.15) were independent predictors of LVBT on multivariate analysis. CONCLUSIONS: The identification of patients at risk of intra-operative LVBT during TAAA surgery is critical as these patients experience a worse outcome. Nevertheless, only few independent predictors are available for clinical practice.

Desmopressin for treatment of platelet dysfunction and reversal of antiplatelet agents: a systematic review and meta-analysis of randomized controlled trials.

Essentials The optimal management of patients with platelet dysfunction undergoing surgery is unclear. This meta-analysis compared perioperative administration of desmopressin to placebo. Desmopressin reduced red cell transfusions, blood loss and risk of re-operation due to bleeding. There were too few events to determine if there was a change in the risk of thrombotic events. SUMMARY: Background Platelet dysfunction, including that caused by antiplatelet agents, increases the risk of perioperative bleeding. The optimal management of patients with platelet dysfunction undergoing surgery is unclear. Objectives To assess whether desmopressin reduces perioperative allogeneic red cell transfusion and bleeding in patients with platelet dysfunction. Patients/Methods We searched for randomized controlled trials in The Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, the Transfusion Evidence Library and the ISI Web of Science to 7th July 2016. Data were pooled using mean difference (MD), relative risks or Peto odds ratios (pOR) using a random-effects model. Results Ten trials with 596 participants were identified, all in the setting of cardiac surgery. Platelet dysfunction was due to antiplatelet agents in six trials and cardiopulmonary bypass in four trials. Patients treated with desmopressin were transfused with fewer red cells (MD, -0.65 units; 95% Confidence Interval [CI], -1.16 to -0.13 units), lost less blood (MD, -253.93 mL; 95% CI, -408.01 to -99.85 mL) and had a lower risk of re-operation due to bleeding (pOR, 0.39; 95% CI, 0.18-0.84). The GRADE quality of evidence was very low to moderate, suggesting considerable uncertainty over the results Conclusions Desmopressin may be a useful agent to reduce bleeding and transfusion requirements for people with platelet dysfunction or with a history of recent antiplatelet drug administration undergoing cardiac surgery.