Reassessing the dosing of cefoxitin prophylaxis during major abdominal surgery: insights from microdialysis and population pharmacokinetic modelling.

OBJECTIVES: Cefoxitin is frequently used for surgical antibiotic prophylaxis (SAP). Using microdialysis, we evaluated whether the currently recommended dosing regimen is appropriate to maintain cefoxitin subcutaneous tissue concentrations above the MIC for pathogens involved in abdominal surgical site infection. METHODS: Data from eight patients undergoing major abdominal surgery were analysed using population pharmacokinetic modelling, and Monte Carlo simulations were conducted to determine the PTA for aerobic and anaerobic pathogens. ClinicalTrials.gov: NCT02703857. RESULTS: Only 2.3% and 47.4% of the simulated patients maintained cefoxitin subcutaneous concentrations above the MIC breakpoint for anaerobic (MIC = 16 mg/L) and aerobic (MIC = 8 mg/L) pathogens, respectively. New simulations with administration of a loading dose followed by a constant infusion of cefoxitin were conducted and demonstrate that, notwithstanding using the same total dose per unit of time, continuous infusion of cefoxitin can cover aerobes in 96.6% of the simulated patients, but remains insufficient for anaerobic bacteria. CONCLUSIONS: The recommended dosing regimen of cefoxitin is insufficient for covering the usual bacteria during abdominal surgery. Administration of a loading dose followed by a constant infusion should be considered for aerobic bacteria and cefoxitin should be avoided as SAP for anaerobic bacteria.

Multicentre, open-label, randomised, controlled clinical trial comparing 2% chlorhexidine-70% isopropanol and 5% povidone iodine-69% ethanol for skin antisepsis in reducing surgical-site infection after cardiac surgery: the CLEAN 2 study protocol.

INTRODUCTION: Surgical-site infection (SSI) is the second most frequent cause of healthcare-associated infection worldwide and is associated with increased morbidity, mortality and healthcare costs. Cardiac surgery is clean surgery with low incidence of SSI, ranging from 2% to 5%, but with potentially severe consequences.Perioperative skin antisepsis with an alcohol-based antiseptic solution is recommended to prevent SSI, but the superiority of chlorhexidine (CHG)-alcohol over povidone iodine (PVI)-alcohol, the two most common alcohol-based antiseptic solutions used worldwide, is controversial. We aim to evaluate whether 2% CHG-70% isopropanol is more effective than 5% PVI-69% ethanol in reducing the incidence of reoperation after cardiac surgery. METHODS AND ANALYSIS: The CLEAN 2 study is a multicentre, open-label, randomised, controlled clinical trial of 4100 patients undergoing cardiac surgery. Patients will be randomised in 1:1 ratio to receive either 2% CHG-70% isopropanol or 5% PVI-69% ethanol for perioperative skin preparation. The primary endpoint is the proportion of patients undergoing any re-sternotomy between day 0 and day 90 after initial surgery and/or any reoperation on saphenous vein/radial artery surgical site between day 0 and day 30 after initial surgery. Data will be analysed on the intention-to-treat principle. ETHICS AND DISSEMINATION: This protocol has been approved by an independent ethics committee and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EudraCT 2017-005169-33 and NCT03560193.

Intra-operative cutaneous temperature monitoring with zero-heat-flux technique (3M SpotOn) in comparison with oesophageal and arterial temperature: A prospective observational study.

BACKGROUND: Continuous monitoring of core temperature is essential during major surgery as a way of improving patient safety. Oesophageal probes or specific arterial catheters are invasive methods used in this setting. A new noninvasive device based on zero-heat-flux (ZHF) technique (SpotOn) seems promising but has been poorly investigated during rapid core temperature changes (RCTC). OBJECTIVE: To assess the accuracy of a SpotOn sensor vs. an oesophageal probe or specific arterial catheter during a slow change in core temperature of less than 1 °C within 30 min and RCTC ≥ 1 °C within 30 min. DESIGN: Prospective observational study. SETTING: Operating rooms at the University Hospital of Poitiers, France. PATIENTS: Fifty patients scheduled for major abdominal surgery under general anaesthesia were enrolled from June 2015 to March 2016. Data from 49 patients were finally analysed. Among these, 15 patients were treated with hyperthermic intraperitoneal chemotherapy. INTERVENTION: Each patient had a ZHF sensor placed on the skin surface of the forehead (TempZHF) and an oesophageal probe (TempEso) used as a reference method. Twenty-two patients also had a thermodilution arterial catheter (TempArt) placed in the axillary artery. MAIN OUTCOME MEASURES: Core temperature was continuously recorded from the three devices after induction of anaesthesia. Comparison of temperature measurements between methods was made using the Bland and Altman method during two separate periods according to the speed of core temperature changes. RESULTS: Compared with TempEso, bias and limits of agreement for TempZHF were 0.1 ±â€Š0.5 °C during slow core temperature changes periods and 0.6 ±â€Š1.8 °C during RCTC periods (P = 0.0002). Compared with TempArt, these values were -0.1 ±â€Š0.4 and 0.5 ±â€Š1.7 °C, respectively (P = 0.0039). The ZHF sensor was well tolerated. CONCLUSION: A SpotOn sensor using the ZHF method seems reliable for core temperature monitoring during abdominal surgery when variations in core temperature are slow rather than rapid. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02869828.

Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery: A Randomized Clinical Trial.

IMPORTANCE: It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery. OBJECTIVE: To evaluate whether noninvasive ventilation improves outcomes among patients developing hypoxemic acute respiratory failure after abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, randomized, parallel-group clinical trial conducted between May 2013 and September 2014 in 20 French intensive care units among 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure (partial oxygen pressure <60 mm Hg or oxygen saturation [SpO2] ≤90% when breathing room air or <80 mm Hg when breathing 15 L/min of oxygen, plus either [1] a respiratory rate above 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing) if it occurred within 7 days after surgical procedure. INTERVENTIONS: Patients were randomly assigned to receive standard oxygen therapy (up to 15 L/min to maintain SpO2 of 94% or higher) (n = 145) or NIV delivered via facial mask (inspiratory pressure support level, 5-15 cm H2O; positive end-expiratory pressure, 5-10 cm H2O; fraction of inspired oxygen titrated to maintain SpO2 ≥94%) (n = 148). MAIN OUTCOMES AND MEASURES: The primary outcome was tracheal reintubation for any cause within 7 days of randomization. Secondary outcomes were gas exchange, invasive ventilation-free days at day 30, health care-associated infections, and 90-day mortality. RESULTS: Among the 293 patients (mean age, 63.4 [SD, 13.8] years; n=224 men) included in the intention-to-treat analysis, reintubation occurred in 49 of 148 (33.1%) in the NIV group and in 66 of 145 (45.5%) in the standard oxygen therapy group within+ 7 days after randomization (absolute difference, -12.4%; 95% CI, -23.5% to -1.3%; P = .03). Noninvasive ventilation was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (25.4 vs 23.2 days; absolute difference, -2.2 days; 95% CI, -0.1 to 4.6 days; P = .04), while fewer patients developed health care-associated infections (43/137 [31.4%] vs 63/128 [49.2%]; absolute difference, -17.8%; 95% CI, -30.2% to -5.4%; P = .003). At 90 days, 22 of 148 patients (14.9%) in the NIV group and 31 of 144 (21.5%) in the standard oxygen therapy group had died (absolute difference, -6.5%; 95% CI, -16.0% to 3.0%; P = .15). There were no significant differences in gas exchange. CONCLUSIONS AND RELEVANCE: Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01971892.

Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial.

PURPOSE: To test whether the polymyxin B hemoperfusion (PMX HP) fiber column reduces mortality and organ failure in peritonitis-induced septic shock (SS) from abdominal infections. METHOD: Prospective, multicenter, randomized controlled trial in 18 French intensive care units from October 2010 to March 2013, enrolling 243 patients with SS within 12 h after emergency surgery for peritonitis related to organ perforation. The PMX HP group received conventional therapy plus two sessions of PMX HP. Primary outcome was mortality on day 28; secondary outcomes were mortality on day 90 and a reduction in the severity of organ failures based on Sequential Organ Failure Assessment (SOFA) scores. PRIMARY OUTCOME: day 28 mortality in the PMX HP group (n = 119) was 27.7 versus 19.5% in the conventional group (n = 113), p = 0.14 (OR 1.5872, 95% CI 0.8583-2.935). Secondary endpoints: mortality rate at day 90 was 33.6% in PMX-HP versus 24% in conventional groups, p = 0.10 (OR 1.6128, 95% CI 0.9067-2.8685); reduction in SOFA score from day 0 to day 7 was -5 (-11 to 6) in PMX-HP versus -5 (-11 to 9), p = 0.78. Comparable results were observed in the predefined subgroups (presence of comorbidity; adequacy of surgery, <2 sessions of hemoperfusion) and for SOFA reduction from day 0 to day 3. CONCLUSION: This multicenter randomized controlled study demonstrated a non-significant increase in mortality and no improvement in organ failure with PMX HP treatment compared to conventional treatment of peritonitis-induced SS.

Outcome of acute mesenteric ischemia in the intensive care unit: a retrospective, multicenter study of 780 cases.

BACKGROUND: In the intensive care unit (ICU), the outcomes of patients with acute mesenteric ischemia (AMI) are poorly documented. This study aimed to determine the risk factors for death in ICU patients with AMI. METHODS: A retrospective, observational, non-interventional, multicenter study was conducted in 43 ICUs of 38 public institutions in France. From January 2008 to December 2013, all adult patients with a diagnosis of AMI during their hospitalization in ICU were included in a database. The diagnosis was confirmed by at least one of three procedures (computed tomography scan, gastrointestinal endoscopy, or upon surgery). To determine factors associated with ICU death, we established a logistic regression model. Recursive partitioning analysis was applied to construct a decision tree regarding risk factors and their interactions most critical to determining outcomes. RESULTS: The death rate of the 780 included patients was 58 %. Being older, having a higher sequential organ failure assessment (SOFA) severity score at diagnosis, and a plasma lactate concentration over 2.7 mmol/l at diagnosis were independent risk factors of ICU mortality. In contrast, having a prior history of peripheral vascular disease or an initial surgical treatment were independent protective factors against ICU mortality. Using age and SOFA severity score, we established an ICU mortality score at diagnosis based on the cutoffs provided by recursive partitioning analysis. Probability of survival was statistically different (p < 0.001) between patients with a score from 0 to 2 and those with a score of 3 and 4. CONCLUSION: Acute mesenteric ischemia in ICU patients was associated with a 58 % ICU death rate. Age and SOFA severity score at diagnosis were risk factors for mortality. Plasma lactate concentration over 2.7 mmol/l was also an independent risk factor, but values in the normal range did not exclude the diagnosis of AMI.

Flail chest in polytraumatized patients: surgical fixation using Stracos reduces ventilator time and hospital stay.

OBJECTIVES: Conservative management of patients with flail chest is the treatment of choice. Rib fracture repair is technically challenging; however, with the advent of specially designed molding titanium clips, surgical management has been simplified. Surgical stabilization has been used with good outcomes. We are reporting on our institutional matched-case-control study. METHODS: Between April 2010 and April 2011, ten polytraumatized patients undergoing rib stabilization for flail chest were matched 1 : 1 to 10 control patients by age ±10 years, sex, neurological or vertebral trauma, abdominal injury, and arm and leg fractures. Surgery was realized in the first 48 hours. RESULTS: There were no significant differences between groups for matched data and prognostic scores: injury severity score, revised trauma score, and trauma injury severity score. Ventilator time (142 ± 224 versus 74 ± 125 hours, P = 0.026) and overall hospital stay (142 ± 224 versus 74 ± 125 hours, P = 0.026) were significantly lower for the surgical group after adjustment on prognostic scores. There was a trend towards shorter ICU stay for operative patients (12.3 ± 8.5 versus 9.0 ± 4.3 days, P = 0.076). CONCLUSIONS: Rib fixation with Stracos is feasible and decreases the length of ventilation and hospital stay. A multicenter randomized study is warranted so as to confirm these results and to evaluate impact on pulmonary function status, pain, and quality of life.

Prevalence of iron deficiency on ICU discharge and its relation with fatigue: a multicenter prospective study.

INTRODUCTION: Prevalence of iron deficiency (ID) at intensive care (ICU) admission is around 25 to 40%. Blood losses are important during ICU stay, leading to iron losses, but prevalence of ID at ICU discharge is unknown. ID has been associated with fatigue and muscular weakness, and may thus impair post-ICU rehabilitation. This study assessed ID prevalence at ICU discharge, day 28 (D28) and six months (M6) after and its relation with fatigue. METHODS: We conducted this prospective, multicenter observational study at four University hospitals ICUs. Anemic (hemoglobin (Hb) less than 13 g/dL in male and less than 12 g/dL in female) critically ill adult patients hospitalized for at least five days had an iron profile taken at discharge, D28 and M6. ID was defined as ferritin less than 100 ng/L or less than 300 ng/L together with a transferrin saturation less than 20%. Fatigue was assessed by numerical scale and the Multidimensional Fatigue Inventory-20 questionnaire at D28 and M6 and muscular weakness by a hand grip test at ICU discharge. RESULTS: Among 107 patients (men 77%, median (IQR) age 63 (48 to 73) years) who had a complete iron profile at ICU discharge, 9 (8.4%) had ID. At ICU discharge, their hemoglobin concentration (9.5 (87.7 to 10.3) versus 10.2 (92.2 to 11.7) g/dL, P =0.09), hand grip strength (52.5 (30 to 65) versus 49.5 (15.5 to 67.7)% of normal value, P =0.61) and visual analog scale fatigue scale (57 (40 to 80) versus 60 (47.5 to 80)/100, P =0.82) were not different from non-ID patients. At D28 (n =80 patients) and M6 (n =78 patients), ID prevalence increased (to 25 and 35% respectively) while anemia prevalence decreased (from 100% to 80 and 25% respectively, P <0.0001). ID was associated with increased fatigue at D28, after adjustment for main confounding factors, including anemia (regression coefficient (95%CI), 3.19 (0.74 to 5.64), P =0.012). At M6, this association disappeared. CONCLUSIONS: The prevalence of ID increases from 8% at discharge to 35% six months after prolonged ICU stay (more than five days). ID was associated with increased fatigue, independently of anemia, at D28.

Nefopam pharmacokinetics in patients with end-stage renal disease.

BACKGROUND: Treatment of intense postoperative pain in patients with end-stage renal disease (ESRD) is a recurrent problem for anesthesiologists because of the risk of accumulation of numerous molecules and their metabolites. Nefopam is a potent analgesic metabolized by the liver and weakly eliminated intact in urine that may offer advantages for use in patients with ESRD because it lacks respiratory-depressive effects. However, the effects of renal failure on nefopam disposition have never been investigated. METHODS: We studied 12 ESRD patients (creatinine clearance < 20 mL/min, mean age 57 ± 13 years) having surgery under general anesthesia to create or repair an arteriovenous fistula. Postoperatively, after complete recovery from anesthesia, each patient received a single 20-mg dose of nefopam IV over 30 minutes. Nefopam and desmethyl-nefopam concentrations in plasma samples obtained over 48 hours were determined by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameter values obtained were compared with those of 12 healthy 50- to 60-year-old volunteers who also received a single 20-mg nefopam infusion over 30 minutes using a population pharmacokinetic approach. RESULTS: Healthy volunteers and ESRD patients had comparable demographic characteristics. In comparison with those volunteers, ESRD patients had a lower volume of central compartment (115 and 53 L vs. 264 L for patients not yet hemodialyzed and on chronic hemodialysis, respectively; P < 0.001) and lower mean nefopam clearance (37.0 and 27.3 L/h vs. 52.9 L/h, P < 0.001), resulting in higher mean nefopam peak concentration (121 and 223 ng/mL vs. 61 ng/mL, P < 0.001). CONCLUSIONS: Nefopam distribution and elimination are altered in patients with ESRD, resulting in heightened exposure. To avoid too-high concentration peaks, it is suggested that the daily nefopam dose be reduced by 50%.

Steady-state trough serum and epithelial lining fluid concentrations of teicoplanin 12 mg/kg per day in patients with ventilator-associated pneumonia.

OBJECTIVE: To determine the steady-state trough serum and epithelial lining fluid (ELF) concentrations of teicoplanin 12 mg/kg per day in critically ill patients with ventilator associated pneumonia. DESIGN AND SETTING: Prospective, pharmacokinetic study in the surgical intensive care unit in a university hospital. PATIENTS: Thirteen adult patients with nosocomial bacterial pneumonia on mechanical ventilation were enrolled. INTERVENTIONS: All subjects received a 30-min intravenous infusion of 12 mg/kg teicoplanin every 12 h for 2 consecutive days followed by 12 mg/kg once daily. Teicoplanin concentrations in serum and ELF were determined simultaneously 4-6 days after antibiotic administration started. MEASUREMENTS AND RESULTS: The median total and free concentrations of teicoplanin in serum at trough were 15.9 microg/ml (range 8.8-29.9) and 3.7 (2.0-5.4), respectively. The concentration in ELF was 4.9 (2.0-11.8). CONCLUSIONS: In critically ill patients with ventilator-associated pneumonia the administration of high teicoplanin doses is required to reach sufficient trough antibiotic concentrations in lung tissues at steady state. At that time trough-free concentrations of teicoplanin in serum and ELF are comparable.