Protocol for venoarterial ExtraCorporeal Membrane Oxygenation to reduce morbidity and mortality following bilateral lung TransPlantation: the ECMOToP randomised controlled trial.

INTRODUCTION: Lung transplantation (LTx) aims at improving survival and quality of life for patients with end-stage lung diseases. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as intraoperative support for LTx, despite no precise guidelines for its initiation. We aim to evaluate two strategies of VA-ECMO initiation in the perioperative period in patients with obstructive or restrictive lung disease requiring bilateral LTx. In the control 'on-demand' arm, high haemodynamic and respiratory needs will dictate VA-ECMO initiation; in the experimental 'systematic' arm, VA-ECMO will be pre-emptively initiated. We hypothesise a 'systematic' strategy will increase the number of ventilatory-free days at day 28. METHODS AND ANALYSIS: We designed a multicentre randomised controlled trial in parallel groups. Adult patients with obstructive or restrictive lung disease requiring bilateral LTx, without a formal indication for pre-emptive VA-ECMO before LTx, will be included. Patients with preoperative pulmonary hypertension with haemodynamic collapse, ECMO as a bridge to transplantation, severe hypoxaemia or hypercarbia will be secondarily excluded. In the systematic group, VA-ECMO will be systematically implanted before the first pulmonary artery cross-clamp. In the on-demand group, VA-ECMO will be implanted intraoperatively if haemodynamic or respiratory indices meet preplanned criteria. Non-inclusion, secondary exclusion and VA-ECMO initiation criteria were validated by a Delphi process among investigators. Postoperative weaning of ECMO and mechanical ventilation will be managed according to best practice guidelines. The number of ventilator-free days at 28 days (primary endpoint) will be compared between the two groups in the intention-to-treat population. Secondary endpoints encompass organ failure occurrence, day 28, day 90 and year 1 vital status, and adverse events. ETHICS AND DISSEMINATION: The sponsor is the Assistance Publique-Hôpitaux de Paris. The ECMOToP protocol version 2.1 was approved by Comité de Protection des Personnes Ile de France VIII. Results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT05664204.

Effectiveness of Surgeon-Performed Paravertebral Block Analgesia for Minimally Invasive Thoracic Surgery: A Randomized Clinical Trial.

Importance: In minimally invasive thoracic surgery, paravertebral block (PVB) using ultrasound (US)-guided technique is an efficient postoperative analgesia. However, it is an operator-dependent process depending on experience and local resources. Because pain-control failure is highly detrimental, surgeons may consider other locoregional analgesic options. Objective: To demonstrate the noninferiority of PVB performed by surgeons under video-assisted thoracoscopic surgery (VATS), hereafter referred to as PVB-VATS, as the experimental group compared with PVB performed by anesthesiologists using US-guided technique (PVB-US) as the control group. Design, Setting, and Participants: In this single-center, noninferiority, patient-blinded, randomized clinical trial conducted from September 8, 2020, to December 8, 2021, patients older than 18 years who were undergoing a scheduled minimally invasive thoracic surgery with lung resection including video-assisted or robotic approaches were included. Exclusion criteria included scheduled open surgery, any antalgic World Health Organization level greater than 2 before surgery, or a medical history of homolateral thoracic surgery. Patients were randomly assigned (1:1) to an intervention group after general anesthesia. They received single-injection PVB before the first incision was made in the control group (PVB-US) or after 1 incision was made under thoracoscopic vision in the experimental group (PVB-VATS). Interventions: PVB-VATS or PVB-US. Main Outcomes and Measures: The primary end point was mean 48-hour post-PVB opioid consumption considering a noninferiority range of less than 7.5 mg of opioid consumption between groups. Secondary outcomes included time of anesthesia, surgery, and operating room occupancy; 48-hour pain visual analog scale score at rest and while coughing; and 30-day postoperative complications. Results: A total of 196 patients were randomly assigned to intervention groups: 98 in the PVB-VATS group (mean [SD] age, 64.6 [9.5] years; 53 female [54.1%]) and 98 in the PVB-US group (mean [SD] age, 65.8 [11.5] years; 62 male [63.3%]). The mean (SD) of 48-hour opioid consumption in the PVB-VATS group (33.9 [19.8] mg; 95% CI, 30.0-37.9 mg) was noninferior to that measured in the PVB-US group (28.5 [18.2] mg; 95% CI, 24.8-32.2 mg; difference: -5.4 mg; 95% CI, -∞ to -0.93; noninferiority Welsh test, P ≤ .001). Pain score at rest and while coughing after surgery, overall time, and postoperative complications did not differ between groups. Conclusions and Relevance: PVB placed by a surgeon during thoracoscopy was noninferior to PVB placed by an anesthesiologist using ultrasonography before incision in terms of opioid consumption during the first 48 hours. Trial Registration: ClinicalTrials.gov Identifier: NCT04579276.

OCOSO2: study protocol for a single-blinded, multicentre, randomised controlled trial assessing a central venous oxygen saturation-based goal-directed therapy to reduce postoperative complications in high-risk patients after elective major surgery.

BACKGROUND: Fluid loading-based goal-directed therapy is a cornerstone of anaesthesia management in major surgery. Its widespread application has contributed to a significant improvement in perioperative morbidity and mortality. In theory, only hypovolemic patients should receive fluid therapy. However, to achieve such a diagnosis, a surrogate marker of cardiac output adequacy must be used. Current methods of fluid loading-based goal-directed therapy do not assess cardiac output adequacy. Nowadays, new devices make it possible to continuously monitor central venous oxygen saturation (ScvO2) and therefore, to assess the adequacy of perioperative cardiac output during surgery. In major surgery, ScvO2-based goal-directed therapy can be used to enhance fluid therapy and improve patient outcomes. METHODS: We designed a prospective, randomised, single-blinded, multicentre controlled superiority study with a 1:1 allocation ratio. Patients to be included will be high-risk major surgery patients (> 50 years old, ASA score > 2, major intra-abdominal or intra-thoracic surgery > 90 min). Patients in the control group will undergo standard fluid loading-based goal-directed therapy, as recommended by the guidelines. Patients in the intervention group will have ScvO2-based goal-directed therapy and receive fluid loading only if fluid responsiveness and cardiac output inadequacy are present. The primary outcome will be the Comprehensive Complication Index on day five postoperatively. DISCUSSION: This study is the first to address the issue of cardiac output adequacy in goal-directed therapy. Our hypothesis is that cardiac output optimisation during major surgery achieved by continuous monitoring of the ScvO2 to guide fluid therapy will result in a reduction of postoperative complications as compared with current goal-directed fluid therapy practices. TRIAL REGISTRATION: ClinicalTrials.gov. NCT03828565. Registered on February 4, 2019.

Nicotine Replacement Therapy Does Not Reduce Headaches Following Subarachnoid Hemorrhage: A Propensity Score-Matched Study.

BACKGROUND: A significant number of patients admitted for aneurysmal subarachnoid hemorrhage (aSAH) are active smokers and are at risk of developing nicotine withdrawal symptoms (e.g., cravings, irritability, insomnia, headaches, etc.). This study aimed to evaluate the use of nicotine replacement therapy (NRT) regarding headache severity and analgesics consumption. METHODS: A retrospective study was conducted using prospectively collected data from 2014 to 2019 in the neurointensive care unit of the Hospices Civils in Lyon, France. We performed a propensity score matching analysis. The covariables used were age, sex, initial World Federation of Neurosurgical Societies score, Hijdra sum score, and factors associated with pain following aSAH (history of chronic pain, anxiety, or depression). Smokers received NRT through a transdermal device. The primary end point was headache control. Secondary end points were mean numerical pain rating scale score and analgesics consumption. RESULTS: One hundred and fifty-five patients were included among 523 patients hospitalized for aSAH. Fifty-one patients underwent nicotine substitution and were matched to 51 unsubstituted patients. The headache control rate was not different between the two groups (43.1% vs. 31.4%, p = 0.736). The mean numeric pain rating scale score in the substituted group was 2.2 (1.1-3.5) and 2.4 (1.6-3.1) in the unsubstituted group (p = 0.533). The analgesics consumption (acetaminophen, tramadol, and morphine) was the same in the two groups. CONCLUSIONS: The use of NRT in the acute phase of aSAH does not seem to have an impact on the intensity of headaches or analgesics consumption.

Ultra-early initiation of postoperative rehabilitation in the post-anaesthesia care unit after major thoracic surgery: case-control study.

BACKGROUND: Physiotherapy is a major cornerstone of enhanced rehabilitation after surgery (ERAS) and reduces the development of atelectasis after thoracic surgery. By initiating physiotherapy in the post-anaesthesia care unit (PACU), the aim was to evaluate whether the ultra-early initiation of rehabilitation (in the first hour following tracheal extubation) would improve the outcomes of patients undergoing elective thoracic surgery. METHODS: A case-control study with a before-and-after design was conducted. From a historical control group, patients were paired at a 3:1 ratio with an intervention group. This group consisted of patients treated with the ultra-early rehabilitation programme after elective thoracic surgery (clear fluids, physiotherapy, and ambulation). The primary outcome was the incidence of postoperative atelectasis and/or pneumonia during the hospital stay. RESULTS: After pairing, 675 patients were allocated to the historical control group and 225 patients to the intervention group. A significant decrease in the incidence of postoperative atelectasis and/or pneumonia was found in the latter (11.4 versus 6.7 per cent respectively; P = 0.042) and remained significant on multivariate analysis (OR 0.53, 95 per cent c.i. 0.26 to 0.98; P = 0.045). A subgroup analysis of the intervention group showed that early ambulation during the PACU stay was associated with a further significant decrease in the incidence of postoperative atelectasis and/or pneumonia (2.2 versus 9.5 per cent; P = 0.012). CONCLUSIONS: Ultra-early rehabilitation in the PACU was associated with a decrease in the incidence of postoperative atelectasis and/or pneumonia after major elective thoracic surgery.

Early-stage non-small cell lung cancer beyond life expectancy: Still not too old for surgery?

OBJECTIVE: We investigated on the benefit/risk ratio of surgery in octogenarians with early-stage non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: From 2005-2020, 100 octogenarians were operated on for a clinical stage IA to IIA NSCLC. All patients had undergone whole body PET -scan and brain imaging. Operability was assessed according to current guidelines regarding the cardiopulmonary function. Since 2015, patients followed a dedicated geriatric evaluation pathway. Minimally invasive approaches were used in 66 patients, and a thoracotomy in 34. RESULTS: Clavien-Dindo grade ≥ 4 complications occurred in 15 patients within 90 days, including 7 fatalities. At multivariable analysis, the number of co-morbidities was their single independent prognosticator. Following resection, 24 patients met pathological criteria for adjuvant therapy among whom 3 (12.5 %) received platinum-based chemotherapy. Five-year survival rates were overall (OS) 47 ±â€¯6.3 %, disease-free (DFS) 77.6 ±â€¯5.1 %, and lung cancer-specific (CSS) 74.7 ±â€¯6.3 %. Diabetes mellitus impaired significantly long-term outcomes in these 3 dimensions. OS was improved since the introduction of a dedicated geriatric assessment pathway (72.3 % vs. 6.4 %, P = 0.00002), and when minimally invasive techniques were used (42.3 % vs. 11.3 %; P = 0.02). CSS was improved by the performance of systematic lymphadenectomy (55.3 % vs. 26.9 %; P = 0.04). Multivariable and recursive partitioning analyses showed that a decision tree could be built to predict overall survival on the basis of diabetes mellitus, high co-morbidity index and low ppoDLCO values. CONCLUSIONS: The introduction of a dedicated geriatric assessment pathway to select octogenarians for lung cancer surgery was associated with OS values that are similar to outcomes in younger patients. The use of minimally invasive surgery and the performance of systematic lymphadenectomy were also associated with improved long-term survival. Octogenarians with multiple co-morbid conditions, diabetes mellitus, or low ppo DLCO values may be more appropriately treated with SBRT.

Postoperative morphine consumption and anaesthetic management of patients undergoing video-assisted or robotic-assisted lung resection: a prospective, propensity score-matched study.

BACKGROUND: Robotic assistance is increasingly being used for treatment of early stage of non-small cell lung cancer. Our objectives were to compare the morphine consumption during the postoperative 48 hours after robotic-assisted thoracic surgery and that after video-assisted thoracic surgery as well as compare the patient's haemodynamic and respiratory function during the procedures. METHODS: This observational, prospective study was conducted in a single referral centre for thoracic surgery from January 2016 to March 2017. Patients who were scheduled to undergo surgical lung resection were included. A propensity score based on age, sex, American society of Anesthesiology score was used between groups. Linear regression analyses were used to determine the mean difference in the postoperative morphine consumption. We also compared the haemodynamic and respiratory function during the two procedures. RESULTS: Among the 194 patients included, 105 (54%) and 89 (46%) underwent video and robotic surgery, respectively. Total 75 of each group were matched using the propensity score. The consumption of morphine was 23.0 (16.5-39.0) mg and 33.0 (19.3-46.5) mg (P=0.05) in the video and robotic groups, respectively. Linear regression revealed an average difference ß (95% CI) of 6.76 mg (0.32-13.26) (P=0.04) in the morphine consumption after adjusting for the body mass index and local anaesthetic use. Robotic surgery was associated with worse haemodynamic and respiratory function than video surgery. CONCLUSIONS: As compared with video, robotic surgery was associated with increased use of morphine and greater alteration in the haemodynamic and respiratory functions.

Oropharyngeal and nasopharyngeal decontamination with chlorhexidine gluconate in lung cancer surgery: a randomized clinical trial.

PURPOSE: Respiratory complications are the leading causes of morbidity and mortality after lung cancer surgery. We hypothesized that oropharyngeal and nasopharyngeal decontamination with chlorhexidine gluconate (CHG) would be an effective method to reduce these complications as reported in cardiac surgery. METHODS: In this multicenter parallel-group randomized double-blind placebo-controlled trial, we enrolled consecutive adults scheduled for anatomical pulmonary resection for lung cancer. Perioperative decontamination consisted in oropharyngeal rinse solution (0.12% CHG) and nasopharyngeal soap (4% CHG) or a placebo. The primary outcome measure was the proportion of patients requiring postoperative invasive and/or noninvasive mechanical ventilation (MV). Secondary outcome measures included occurrence of respiratory and non-respiratory healthcare-associated infections (HAIs) and outcomes within 90 days. RESULTS: Between July 2012 and April 2015, 474 patients were randomized. Of them, 24 had their surgical procedure cancelled or withdrew consent. The remaining 450 patients were included in a modified intention-to-treat analysis: 226 were allocated to CHG and 224 to the placebo. Proportions of patients requiring postoperative MV were not significantly different [CHG 14.2%; placebo 15.2%; relative risks (RRs) 0.93; 95% confidence interval (CI) 0.59-1.45; P = 0.76]. Neither of the proportions of patients with respiratory HAIs were different (CHG 13.7%; placebo 12.9%; RRs 1.06; 95% CI 0.66-1.69; P = 0.81). The CHG group had significantly decreased incidence of bacteremia, surgical-site infection and overall Staphylococcus aureus infections. However, there were no significant between-group differences for hospital stay length, change in tracheal microbiota, postoperative antibiotic utilization and outcomes by day 90. CONCLUSIONS: CHG decontamination decreased neither MV requirements nor respiratory infections after lung cancer surgery. Additionally, CHG did not change tracheal microbiota or postoperative antibiotic utilization. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov, number NCT01613365.

Non-adherence to guidelines: an avoidable cause of failure of empirical antimicrobial therapy in the presence of difficult-to-treat bacteria.

PURPOSE: To identify the risk factors of ventilator-associated pneumonia (VAP) due to difficult-to-treat (DTT) bacteria (i.e., Pseudomonas aeruginosa, Acinetobacter baumannii and oxacillin-resistant Staphylococcus aureus), and to assess the rate and the causes of inappropriateness of empirical antimicrobial therapy. METHODS: In an intensive care unit of a university hospital, patients with VAP were empirically treated with antibiotics without activity against DTT bacteria if the patients had no prior hospitalization or prior administration of antibiotics, according to local guidelines. RESULTS: Overall, the empirical antimicrobial therapy was appropriate in 190 (87%) out of 218 patients with VAP. Fifty (23%) patients developed problems due to DTT bacteria. The risk factors for VAP due to DTT bacteria were shock state, prior antimicrobial therapy, prior stay in long-term care facilities and late-onset VAP. Empirical antimicrobial therapy was inappropriate in 20 (40%) patients with VAP due to DTT bacteria and 8 (5%) patients with VAP due to non-DTT (P = 0.001). Guidelines violations (nine patients), bacteria not included in antibiotic spectrum (eight patients) and bacterial resistance (three patients) were the causes of inappropriateness in case of DTT bacteria. CONCLUSION: Despite the abundant information for the treatment of VAP and the establishment of guidelines, too many patients with DTT bacteria received inappropriate antimicrobial therapy. Since 45% of the cases are related to non-adherence to the local protocol, there is room for improvement by implementing educational programs. Also, since DTT bacteria are found in 23% of late-onset VAP, empirical antibiotic treatment should be directed against these pathogens.

Oxygen tissue saturation is lower in nonsurvivors than in survivors after early resuscitation of septic shock.

BACKGROUND: Growing evidence suggests that the microvascular dysfunction is the key element of the pathogenesis of septic shock. This study's purpose was to explore whether the outcome of septic shock patients after early resuscitation using early goal-directed therapy is related to their muscle tissue oxygenation. METHODS: Tissue oxygen saturation (Sto2) was monitored in septic shock patients using a tissue spectrometer (InSpectra Model 325; Hutchinson Technology, Hutchinson, MN). For the purpose of this retrospective study, the Sto2 values were collected at the first measurement done after the macrohemodynamic variables (mean arterial pressure, urine output, central venous saturation in oxygen) were optimized. RESULTS: After the hemodynamic variables were corrected, no difference was observed between the nonsurvivors and survivors, with the exception of pulse oximetry saturation (94% [92-97%] vs. 97% [94-99%], P = 0.04). The Sto2 values were significantly lower in the nonsurvivors than in the survivors (73% [68-82%] vs. 84% [81-90%], P = 0.02). No correlations were found between the Sto2 and Spo2 (P = 0.7). CONCLUSIONS: In septic shock patients, tissue oxygen saturation below 78% is associated with increased mortality at day 28. Further investigations are required to determine whether the correction of an impaired level of tissue oxygen saturation may improve the outcome of these patients.

Long-term outcome in chest trauma.

BACKGROUND: Currently, there are limited data available describing the long-term outcomes of chest trauma survivors. Here, the authors sought to describe chest trauma survivor outcomes 6 months and 1 yr after discharge from the intensive care unit, paying special attention to pulmonary outcomes. METHODS: A cohort of 105 multiple trauma patients with blunt chest trauma admitted to the intensive care unit was longitudinally evaluated. After 6 months, a chest computed tomography scan, pulmonary function testing (PFT), and quality of life were collected in 55 of these patients. A subgroup of 38 patients was followed up for 1 yr. RESULTS: At least one abnormal PFT result was found in 39 patients (71%). Compared with normalized data of the age- and sex-matched population, physical function was decreased in 38 patients (70%). The 6-min walk distance was reduced for 29 patients (72%). Although pathologic images were observed on the chest computed tomography scan from 33 patients (60%), no relation was found between PFT and computed tomography. A ratio of arterial oxygen pressure to inspired oxygen fraction less than 200 at admission to the intensive care unit predicted an abnormal PFT result at 6 months. One year after discharge from the intensive care unit, paired comparisons showed a significant increase in forced vital capacity (P = 0.02) and Karnofsky Performance Status (P < 0.001). CONCLUSIONS: Survivors of multiple traumas including chest trauma demonstrate a persistent decrease in the 6-min walk distance, impairment on PFT, and reduced pulmonary-specific quality of life.