Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE): study protocol for a randomized controlled trial

Background: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients. Methods/design The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index ≥35 kg/m2 scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH2O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH2O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint. Discussion To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs. Trial registration ClinicalTrials.gov identifier: NCT02148692. Registered on 23 May 2014; last updated 7 June 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1929-0) contains supplementary material, which is available to authorized users

Anxiety and its predictive value for pain and regular analgesic intake after lumbar disc surgery - a prospective observational longitudinal study

Abstract Background Ongoing pain after surgery is a major problem and influences recovery and the quality of life of the patient. Associations between anxiety and their impact on postoperative pain after herniated disc surgery have been reported, but the results are inconsistent. The aim of the present longitudinal study was to evaluate the predictive value of preoperative anxiety for postoperative ongoing pain and prolonged analgesic intake after herniated disc surgery. Methods 106 patients with lumbar disc herniation were evaluated in the study. Anxiety was measured with the Generalized Anxiety Disorder 7-Item Scale (GAD-7) before surgery. Pain intensity was assessed on a numeric rating scale (NRS) at baseline, 6-weeks and 6-months after surgery. Regression analysis was performed to identify independent predictors of pain and regular utilization of analgesics up to 6 months after surgery while controlling for confounding variables. Results 42.5% of the patients were rated as anxiety cases (sum scores GAD-7 > 5), mean scores of anxiety showed mild to moderate symptom severity, and 43% suffered from chronic pain before surgery. Six months after surgery, 55.6% of the patients indicated pain levels of 4/10 (NRS) or higher and about 40% still took pain medication on a regular basis, regardless of their preoperative classification as anxiety-case (37.7% and 41.5%). The preoperative pain level was statistically significant for ongoing postsurgical pain in all four analyses (p < 0.001). With binary logistic regression analyses, preoperative pain intensity, but neither demographic factors nor preoperative anxiety, was identified as predictor for postoperative pain and need for analgesic medication up to 6 months after lumbar disc surgery. Conclusion We found no evidence for the presence of anxiety before disc surgery being a prognostic factor for ongoing pain and regular postoperative intake of analgesics. Only preoperative pain intensity was predictive for increased pain and continued need for analgesic medication up to 6 months after lumbar disc surgery. Trial registration Clinicaltrials.gov NCT01488617. Registered 6 December 2011

Prevalence of pain 6 months after surgery : a prospective observational study

Background Pain after surgery is a major issue for patient discomfort and often associated with delayed recovery. The aim of the present study was to evaluate the prevalence of pain and requirement for analgesics up to 6 months after elective surgery, independent if new pain symptoms occurred after surgery or if preoperative pain persisted in the postoperative period. Methods A prospective observational single center cohort study was conducted between January 2012 and August 2013. Eligible patients were scheduled to undergo elective surgical interventions including joint (hip, knee arthroplasty), back (nucleotomy, spondylodesis), or urological surgery (cystectomy, prostatectomy, nephrectomy). Pain was assessed on an 11-point numerical rating scale (NRS) before, on postoperative day 2 and 6 months after surgery. Clinical information was collected with structured questionnaires and by telephone interview. Results Six hundred and forty-four patients gave informed consent, including 54.4 % men (mean age 62.2, SD 14.3). Higher preoperative pain scores were found in patients undergoing joint (mean 7.6; 95 % confidence interval [CI]: 7.2–8.0) and back surgery (mean 7.1, CI: 6.8–7.5) than in patients prior to urological surgery (mean 2.3; CI: 1.8–2.8). After 6 months, about 50 % of patients after joint or back surgery indicated pain levels ≥3/10, compared to 15.9 % of patients after urological surgery (p < .001). 35.3 % of the patients after joint surgery and 41.3 % after back surgery still use pain medication 6 months postoperatively, in contrast to 7.3 % of patients after urological surgery. 13.6 % of patients who underwent back surgery indicated the regular intake of opioids. Conclusions Our results reveal that a significant percentage of patients undergoing procedures in joint or back surgery still need pain medication up to 6 months postoperatively due to ongoing pain symptoms. Improved monitoring of pain management is warranted, especially after discharge from hospital, to improve long-term results

Additional file 1: of Anxiety and its predictive value for pain and regular analgesic intake after lumbar disc surgery - a prospective observational longitudinal study

Attachtment A GAD-7. (DOC 24 kb

Additional file 1: of Prevalence of pain 6Â months after surgery: a prospective observational study

Description of variables. Data set includes socio-demographic pain related, anesthesia-related data as well as data on pain medication. (XLSX 85 kb

Kinetics of plasma biomarkers of inflammation and lung injury in surgical patients with or without postoperative pulmonary complications

BACKGROUND Postoperative pulmonary complications (PPCs) are common after major abdominal surgery. The kinetics of plasma biomarkers could improve identification of patients developing PPCs, but the kinetics may depend on intraoperative ventilator settings. OBJECTIVE To test whether the kinetics of plasma biomarkers are capable of identifying patients who will develop PPCs, and whether the kinetics depend on the intraoperative level of positive end-expiratory pressure (PEEP). DESIGN A preplanned substudy of a randomised controlled trial. SETTING Operation room of five centres. PATIENTS Two hundred and forty-two adult patients scheduled for abdominal surgery at risk of developing PPCs. INTERVENTIONS High (12cmH 2 O) versus low ( 642cmH 2 O) levels of PEEP. MAIN OUTCOME MEASURES Individual PPCs were combined as a composite endpoint. Plasma samples were collected before surgery, directly after surgery and on the fifth postoperative day. The levels of the following were measured: tumour necrosis factor (TNF)-\u3b1, interleukin (IL)-6 and IL-8, the soluble form of the Receptor for Advanced Glycation End-products (sRAGE), Surfactant Protein (SP)-D, Clara Cell protein (CC)-16 and Krebs von den Lungen 6 (KL6). RESULTS Blood sampling was complete in 242 patients: 120 patients in the high PEEP group and 122 patients in the low PEEP group. Increases in plasma levels of TNF- IL-6, IL-8 and CC-16, and a decrease in plasma levels of SP-D were greater in patients who developed PPCs; however, the area under the receiver operating characteristic curve was low for all biomarkers. CC-16 was the only biomarker whose level increased more in patients who had received high levels of PEEP. CONCLUSION In patients undergoing abdominal surgery and at risk of developing PPCs, plasma levels of biomarkers for inflammation or lung injury showed distinct kinetics with development of PPCs, but none of the biomarkers showed sufficient prognostic value. The use of high levels of PEEP was associated with increased levels of CC-16, suggesting lung overdistension. TRIAL REGISTRATION The PROVHILO trial, including this substudy, was registered at clinicaltrials.gov (NCT01441791)

Association between pre-operative biological phenotypes and postoperative pulmonary complications: An unbiased cluster analysis

BACKGROUND: Biological phenotypes have been identified within several heterogeneous pulmonary diseases, with potential therapeutic consequences. OBJECTIVE: To assess whether distinct biological phenotypes exist within surgical patients, and whether development of postoperative pulmonary complications (PPCs) and subsequent dependence of intra-operative positive end-expiratory pressure (PEEP) differ between such phenotypes. SETTING: Operating rooms of six hospitals in Europe and USA. DESIGN: Secondary analysis of the 'PROtective Ventilation with HIgh or LOw PEEP' trial. PATIENTS: Adult patients scheduled for abdominal surgery who are at risk of PPCs. INTERVENTIONS: Measurement of pre-operative concentrations of seven plasma biomarkers associated with inflammation and lung injury. MAIN OUTCOME MEASURES: We applied unbiased cluster analysis to identify biological phenotypes. We then compared the proportion of patients developing PPCs within each phenotype, and associations between intra-operative PEEP levels and development of PPCs among phenotypes. RESULTS: In total, 242 patients were included. Unbiased cluster analysis clustered the patients within two biological phenotypes. Patients with phenotype 1 had lower plasma concentrations of TNF-\u3b1 (3.8 [2.4 to 5.9] vs. 10.2 [8.0 to 12.1]\u200apg\u200aml; P\u200a<\u200a0.001), IL-6 (2.3 [1.5 to 4.0] vs. 4.0 [2.9 to 6.5]\u200apg\u200aml; P\u200a<\u200a0.001) and IL-8 (4.7 [3.1 to 8.1] vs. 8.1 [6.0 to 13.9]\u200apg\u200aml; P\u200a<\u200a0.001). Phenotype 2 patients had the highest incidence of PPC (69.8 vs. 34.2% in type 1; P\u200a<\u200a0.001). There was no interaction between phenotype and PEEP level for the development of PPCs (43.2% in high PEEP vs. 25.6% in low PEEP in phenotype 1, and 73.6% in high PEEP and 65.7% in low PEEP in phenotype 2; P for interaction\u200a=\u200a0.503). CONCLUSION: Patients at risk of PPCs and undergoing open abdominal surgery can be clustered based on pre-operative plasma biomarker concentrations. The two identified phenotypes have different incidences of PPCs. Biologic phenotyping could be useful in future randomised controlled trials of intra-operative ventilation. TRIAL REGISTRATION: The PROtective Ventilation with HIgh or LOw PEEP trial, including the substudy from which data were used for the present analysis, was registered at ClinicalTrials.gov (NCT01441791)

Improve hip fracture outcome in the elderly patient (iHOPE) : a study protocol for a pragmatic, multicentre randomised controlled trial to test the efficacy of spinal versus general anaesthesia

Introduction: Hip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse. Methods and analysis: The iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner after hospital discharge and inhospital. The primary endpoint will be assessed by telephone interview and comprises the time to the first occurring event of the binary composite outcome of all-cause mortality or new-onset serious cardiac and pulmonary complications within 30 postoperative days. In-hospital secondary endpoints, assessed via in-person interviews and medical record review, include mortality, perioperative adverse events, delirium, satisfaction, walking independently, length of hospital stay and discharge destination. Telephone interviews will be performed for long-term endpoints (all-cause mortality, independence in walking, chronic pain, ability to return home cognitive function and overall health and disability) at postoperative day 30±3, 180±45 and 365±60. Ethics and dissemination: iHOPE has been approved by the leading Ethics Committee of the Medical Faculty of the RWTH Aachen University on 14 March 2018 (EK 022/18). Approval from all other involved local Ethical Committees was subsequently requested and obtained. Study started in April 2018 with a total recruitment period of 24 months. iHOPE will be disseminated via presentations at national and international scientific meetings or conferences and publication in peer-reviewed international scientific journals. Trial registration number: DRKS00013644; Pre-result