Stefano Busani

Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial.

Importance Despite suggestions of potential harm from unnecessary oxygen therapy, critically ill patients spend substantial periods in a hyperoxemic state. A strategy of controlled arterial oxygenation is thus rational but has not been validated in clinical practice. Objective To assess whether a conservative protocol for oxygen supplementation could improve outcomes in patients admitted to intensive care units (ICUs). Design, Setting, and Patients Oxygen-ICU was a single-center, open-label, randomized clinical trial conducted from March 2010 to October 2012 that included all adults admitted with an expected length of stay of 72 hours or longer to the medical-surgical ICU of Modena University Hospital, Italy. The originally planned sample size was 660 patients, but the study was stopped early due to difficulties in enrollment after inclusion of 480 patients. Interventions Patients were randomly assigned to receive oxygen therapy to maintain Pao2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation (Spo2) between 94% and 98% (conservative group) or, according to standard ICU practice, to allow Pao2 values up to 150 mm Hg or Spo2 values between 97% and 100% (conventional control group). Main Outcomes and Measures The primary outcome was ICU mortality. Secondary outcomes included occurrence of new organ failure and infection 48 hours or more after ICU admission. Results A total of 434 patients (median age, 64 years; 188 [43.3%] women) received conventional (n = 218) or conservative (n = 216) oxygen therapy and were included in the modified intent-to-treat analysis. Daily time-weighted Pao2 averages during the ICU stay were significantly higher (P < .001) in the conventional group (median Pao2, 102 mm Hg [interquartile range, 88-116]) vs the conservative group (median Pao2, 87 mm Hg [interquartile range, 79-97]). Twenty-five patients in the conservative oxygen therapy group (11.6%) and 44 in the conventional oxygen therapy group (20.2%) died during their ICU stay (absolute risk reduction [ARR], 0.086 [95% CI, 0.017-0.150]; relative risk [RR], 0.57 [95% CI, 0.37-0.90]; P = .01). Occurrences were lower in the conservative oxygen therapy group for new shock episode (ARR, 0.068 [95% CI, 0.020-0.120]; RR, 0.35 [95% CI, 0.16-0.75]; P = .006) or liver failure (ARR, 0.046 [95% CI, 0.008-0.088]; RR, 0.29 [95% CI, 0.10-0.82]; P = .02) and new bloodstream infection (ARR, 0.05 [95% CI, 0.00-0.09]; RR, 0.50 [95% CI, 0.25-0.998; P = .049). Conclusions and Relevance Among critically ill patients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy vs conventional therapy resulted in lower ICU mortality. These preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of this approach. Trial Registration clinicaltrials.gov Identifier: NCT01319643.

Perioperative Red Blood Cell Transfusion and Outcome in Stable Patients after Elective Major Vascular Surgery

OBJECTIVES Definitive evidence that red blood cell transfusion improves outcome after vascular surgery is lacking. The aims of the study were to determine, among stable consecutive patients who underwent elective major vascular surgery, (1) the association between postoperative transfusion and 30-day death, myocardial infarction, and both, and (2) and if this association differs according to the presence of postoperative anaemia (haemoglobin value less than 9.0 g/dL within 7 days after surgery). METHODS A retrospective observational study was conducted on 359 patients prospectively screened according to the ACC/AHA guidelines for preoperative risk in non-cardiac surgery. Main outcome was 30-day death; secondary outcomes 30-day myocardial infarction, and composite of 30-day myocardial infarction or death. RESULTS Of the patients included, 95 (26.5%) received at least one unit of red blood cells. Patients who received transfusion had a significantly increased hazard of 30-day death (hazard ratio [HR] 11.72, 95% confidence interval [CI] 3.92-35.10; p<0.0001), myocardial infarction (HR 3.3, 95% CI 1.7-6.1; p=0.0003), and both (HR 4.0 95% CI 2.2-7.3; p<0.0001). Such associations held even after adjusting for baseline characteristics, surgical risk, bleeding, and propensity to receive transfusion. There was a significant interaction between transfusion and postoperative anaemia (p=0.012). In patients without anaemia, transfusion was associated with higher risk of 30-day death (HR 19.20, 95% CI 3.99-92.45; p=0.007), myocardial infarction (HR 5.05, 95% CI 2.23-11.44; p=0.0001), and both. Conversely, in patients with anaemia this association was not significant. CONCLUSIONS In patients who underwent elective major vascular surgery, perioperative transfusion was associated with a significantly increased risk of 30-day events which was more attributable to patients with lesser degree of anaemia. Our data caution against the use of liberal transfusion in stable vascular surgery patients.

Effect of Performance Improvement Programs on Compliance with Sepsis Bundles and Mortality: A Systematic Review and Meta-Analysis of Observational Studies

Background Several reports suggest that implementation of the Surviving Sepsis Campaign (SSC) guidelines is associated with mortality reduction in sepsis. However, adherence to the guideline-based resuscitation and management sepsis bundles is still poor. Objective To perform a systematic review of studies evaluating the impact of performance improvement programs on compliance with Surviving Sepsis Campaign (SSC) guideline-based bundles and/or mortality. Data Sources Medline (PubMed), Scopus and Intercollegiate Studies Institute Web of Knowledge databases from 2004 (first publication of the SSC guidelines) to October 2014. Study Selection Studies on adult patients with sepsis, severe sepsis or septic shock that evaluated changes in compliance to individual/combined bundle targets and/or mortality following the implementation of performance improvement programs. Interventions may consist of educational programs, process changes or both. Data Extraction Data from the included studies were extracted independently by two authors. Unadjusted binary data were collected in order to calculate odds ratios (OR) for compliance to individual/combined bundle targets. Adjusted (if available) or unadjusted data of mortality were collected. Random-effects models were used for the data synthesis. Results Fifty observational studies were selected. Despite high inconsistency across studies, performance improvement programs were associated with increased compliance with the complete 6-hour bundle (OR = 4.12 [95% confidence interval 2.95-5.76], I2 = 87.72%, k = 25, N = 50,081) and the complete 24-hour bundle (OR = 2.57 [1.74-3.77], I2 = 85.22%, k = 11, N = 45,846) and with a reduction in mortality (OR = 0.66 [0.61-0.72], I2 = 87.93%, k = 48, N = 434,447). Funnel plots showed asymmetry. Conclusions Performance improvement programs are associated with increased adherence to resuscitation and management sepsis bundles and with reduced mortality in patients with sepsis, severe sepsis or septic shock.

Levosimendan in cardiac failure after subarachnoid hemorrhage.

The aim of this study is to report the development of cardiac failure after subarachnoid hemorrhage (SAH) with recovery of heart and cerebral function. This is a case report of a 38-year-old woman who was admitted to the intensive care unit (ICU) at Policlinico di Modena, Italy. This woman developed a deep state of coma because of severe SAH. After cerebral hemorrhage, patient showed a cardiogenic shock, which needed invasive monitoring. Cerebral perfusion pressure had to be restored, so fluids, dopamine, norepinephrine, and dobutamine were in administered sequentially. Despite these supportive treatments, hemodynamic parameters further worsened and echocardiography showed a global depressed left ventricular (LV) contraction with poor ejection fraction (EF) and restrictive type of LV relaxation pattern. Twenty-four hours after ICU admission, levosimendan was started with the aim to improve cardiac function because of the refractoriness of all other treatments. Eight hours after levosimendan infusion, cardiac function improved and, within the after 24 hours, EF and LV relaxation pattern recovered. Neurologic state and computed tomography images improved day by day, and after 9 days from the ICU admission, we transferred the patient to the neurosurgical ward with very good neurologic conditions and no deficits in motility. The conventional management of post-SAH cardiovascular failure is based on the use of norepinephrine, dobutamine, and high amount of fluids. This strategy did not provide any improvement, so we decided for levosimendan infusion to counteract myocardial stunning. The improvement in cardiac EF, LV wall motion, and filling pressure observed in our patient could be explained due to the antistunning triple-mechanism action of levosimendan. Data available on the levosimendan effectiveness in patients with SAH and its effect on intracranial pressure are still lacking, but we think that neurogenic cardiac failure can be treated at first with levosimendan.

Acute Renal Failure and Renal Replacement Therapy in the Postoperative Period of Orthotopic Liver Transplant Patients Versus Nonelective Abdominal Surgery Patients

Acute renal failure (ARF) often complicates the postoperative period of patients undergoing orthotopic liver transplantation (OLT); it is habitually associated with high mortality rates. Similarly, patients undergoing major nonelective abdominal surgery are prone to ARF because of their frequent preexistent morbidities, abdominal sepsis, and needed for extended surgical procedures. The aim of this study was to evaluate the incidence of ARF and use of renal replacement therapy (RRT) among OLT versus nonelective abdominal surgery patients and associations with clinical outcomes. We studied all the patients admitted to a surgical intensive care unit (ICU) from January 2008 to December 2009 after OLT or nonelective abdominal surgery. The inclusion criteria were an ICU stay of at least 48 hours and without prior end-stage renal failure. OLT patients (n=84) were younger and less severly ill than surgery patients (n=60). ARF occurrence was lower among the OLT (29%) than the surgery group (47%) requiring RRT in 71% and 53% of patients due to ARF, respectively. The ICU mortality of ARF patients in both groups (29% OLT and 51% surgery) were greater than among subjects without ARF (2% and 6%). The occurrence of ARF is common among these two patient groups, and associated with increased risk of death among in surgery (+45%) versus in OLT (+27%) patients.

Two‐stage liver transplantation: an effective procedure in urgent conditions

Montalti R, Busani S, Masetti M, Girardis M, Di Benedetto F, Begliomini B, Rompianesi G, Rinaldi L, Ballarin R, Pasetto A, Gerunda GE. Two‐stage liver transplantation: an effective procedure in urgent conditions.
Clin Transplant 2010: 24: 122–126.

Unexpected death: Anaphylactic intraoperative death due to Thymoglobulin carbohydrate excipient

Anaphylactic shock is a life-threatening allergic response characterized by severe hypotension, inducing tissue hypoperfusion with possible multi-organ failure and death. We describe the first case of fatal intra-operative anaphylactic shock due to prolonged infusion of Thymoglobulin during Orthotopic Liver Transplantation (OLT), resulting from recruitment of both mastocytes and basophils, activated and degranulated. Post-mortem serological analysis on a preserved, pre-OLT sample of the patients blood revealed specific IgE against carbohydrate cross-reactive determinants (CCDs), such as MUXF3 and nAna c2, proving that anaphylactic reaction was triggered by the Thymoglobulin carbohydrate excipient (sugar alcohol mannitol), rather than anti-thymocyte globulin itself. Our findings are consistent with scientific data reported in the literature, where only one case of non-fatal anaphylaxis to Thymoglobulin has been described, despite the existence of proven cases of anaphylactic reaction to mannitol. This case highlights the need to pay particular attention in future not only to active substances but also to drug excipients, above all during intra-operative drug delivery. In view of the important role played by basophils in this kind of anaphylaxis, the basophil activation test (BAT) could prove useful in preventing anaphylactic death from CCDs.

Recombinant activated factor VII in critical bleeding after orthotopic liver transplantation.

Critical bleeding throughout the intraoperative phase of orthotopic liver transplantation (OLT) strongly increases patient mortality and intensive care unit (ICU) stay. The aim of this study was to report our experience on the use of recombinant activated factor VII (rFVIIa) in postoperative critical bleeding after OLT. In 7 patients with persistent severe bleeding after application of a standard transfusion protocol, we administered a 90 microg/kg bolus of rFVIIa and if necessary eventually repeated it after 3 hours. We recorded the blood loss and the need for transfusions before and after the rFVIIa therapy. Blood losses and need for platelets significantly decreased after rFVIIa administration; a nonsignificant decrease in red blood cells and fresh frozen plasma transfusions also occurred. In 6 patients treatment with rFVIIa was effective; only 1 patient died because of hemorrhagic shock and no thromboses were detected among the treated patients. Awaiting stronger evidence from randomized controlled trials, we suggest that in some challenging cases of massive bleeding rFVIIa should be considered a useful option to control bleeding.

Trends in ventilator-associated pneumonia: Impact of a ventilator care bundle in an Italian tertiary care hospital intensive care unit

BACKGROUND The impact on ventilator-associated pneumonia (VAP) occurrence of a multifaceted program, including progressive strategies for VAP prevention, implemented in an Italian intensive care unit (ICU) is reported. METHODS All adults admitted to the ICU in 2004-2010 with a length of stay ≥72 hours and mechanical ventilation time ≥48 hours were included in the study. Demographics, clinical information, and data on VAP were extracted from the ICU-acquired infection surveillance dataset. A standardized bundle for VAP prevention was implemented in 2004. In 2008, selective digestive tract decontamination (SDD) was added to the protocol. Changes in VAP incidence were evaluated. RESULTS There were 1,372 subjects included in the study. Overall, 156 (11.4%) developed VAP. In the second part of the study VAP incidence decreased from 15.9% to 6.7% (P < .001). Reductions both in early-onset VAP (6.6% to 1.9%; P < .001) and late-onset VAP (9.3% to 4.7%; P = .001) incidence were observed. Multivariate analysis showed a significant reduction in the risk of developing VAP from multidrug-resistant pathogens in the bundle plus SDD period as well (odds ratio, .54; 95% confidence interval, .31-.91). CONCLUSION The implementation of a standardized approach to patient care, including a number of key reduction interventions, was associated with a significant reduction in the risk of developing VAP.

Effectiveness of sepsis bundle application in cirrhotic patients with septic shock: a single-center experience

PURPOSE To evaluate the effect of adherence to evidence-based guidelines of the Surviving Sepsis Campaign (SSC) on the outcome of cirrhotic patients with septic shock admitted to the intensive care unit. METHODS This prospective observational cohort study included 38 patients with documented liver cirrhosis and septic shock admitted to a multidisciplinary intensive care unit at a University Hospital from January 2005 to June 2009. In each patient, the compliance to 4 resuscitation (ie, 6-hour bundle) and to 3 management (i.e. 24-hour bundle) interventions recommended by the SSC guidelines and the 30-day mortality were measured. RESULTS The 6-hour, 24-hour, and all bundles were completed in 50 %, 52%, and 39% of the patients, respectively. The characteristics at admission and the 30-day mortality of patients with all-bundle compliance (n = 15; mortality 86.6%) were similar to those of patients without bundle compliance (n = 23; mortality 78.2%), except for central venous O2 saturation. Unadjusted and adjusted regression analysis showed that none of the single sepsis interventions and bundles were independently associated with 30-day mortality. CONCLUSIONS In our observational study, the adherence to the interventions recommended by the SSC evidence-based guidelines did not provide an improvement in the survival rate of cirrhotic patients with septic shock.