INVESTIGATORS - Benaroya Research Institute



STUDY TITLEThoracic epidural catheter vs. thoracic paravertebral catheter for postoperative pain treatment following elective thoracic surgeryPrincipal InvestigatorsDr Donald E Low MDDepartment of Thoracic Surgery and Thoracic OncologyVirginia Mason Medical Center1100 Ninth AveSeattle WA USA 98101Mail Stop: C6-GSTel: 2062236164Dr Neil Hanson MD,Department of Anesthesiology,Virginia Mason Medical Center,1100 Ninth AveSeattle WA USA 98101Mail Stop: B2-ANTel: 2062236980Dr Fredrik Klevebro, MD, PhD Department of Thoracic Surgery and Thoracic OncologyVirginia Mason Medical Center1100 Ninth AveSeattle WA USA 98101Mail Stop: C6-GSTel: 20622365528CONTENTS TOC \o "1-3" \h \z \u A.INVESTIGATORS PAGEREF _Toc503536829 \h 3B.SPECIFIC AIMS PAGEREF _Toc503536830 \h 4C.BACKGROUND AND SIGNIFICANCE PAGEREF _Toc503536831 \h 5D.RESEARCH DESIGN AND METHODS PAGEREF _Toc503536832 \h 9E.PROTECTION OF HUMAN SUBJECTS PAGEREF _Toc503536833 \h 14INVESTIGATORSPrincipal investigatorsDr Donald Low MD, Department of Thoracic Surgery and Thoracic Oncology, Virginia Mason Medical Center, Seattle, USADr Neil Hanson MD, Department of Anesthesiology, Virginia Mason Medical Center, Seattle, USADr Fredrik Klevebro MD PhD, Department of Thoracic Surgery and Thoracic Oncology, Virginia Mason Medical Center, Seattle, USACo-investigatorsDr Daniel Warren MD, Department of Anesthesiology, Virginia Mason Medical Center, Seattle, USADr Sara Nikravan MD, Department of Anesthesiology, Virginia Mason Medical Center, Seattle, USADr Joseph Neal MD, Department of Anesthesiology, Virginia Mason Medical Center, Seattle, USADr Madhan Kumar Kuppusamy MD, Department of Thoracic Surgery and Thoracic Oncology, Virginia Mason Medical Center, Seattle, USADr Michal Hubka MD, Department of Thoracic Surgery and Thoracic Oncology, Virginia Mason Medical Center, Seattle, USADr Lindsay Pharmer MD, Department of Anesthesiology, Virginia Mason Medical Center, Seattle, USADr Wyndam Strodtbeck MD, Department of Anesthesiology, Virginia Mason Medical Center, Seattle, USASPECIFIC AIMSHypothesisThoracic paravertebral pain catheters can effectively be used for postoperative pain control after open or minimally invasive thoracic surgery and will reduce the risk for postoperative hypotension compared to a thoracic epidural pain catheter.Study aimsTo compare pain control in postoperative thoracic patients between radiologically verified paravertebral pain catheter and epidurogram verified epidural catheter.To determine if thoracic paravertebral pain catheters induce less postoperative hypotension compared to epidural pain catheters. To evaluate the effect of paravertebral pain catheter compared to epidural pain catheter concerning: postoperative total need for intravenous fluid treatment for the first 48 postoperative hours, length of hospital stay, patient reported satisfaction (EORTC IN-PATSAT32), total dose of postoperative opioids (reported in morphine equivalents), and need for change in postoperative pain treatment regimen. BACKGROUND AND SIGNIFICANCEFor the patients undergoing elective thoracic surgery, postoperative pain management is a crucial component of postoperative recovery. Incision into the pleural cavity through the ribs may render significant postoperative pain through trauma to the parietal pleura, musculoskeletal tissue and intercostal nerves. Adequate pain control is important in facilitating a patient’s ability to comply with early mobilization and respiratory exercises. These are key components of recovery. Inadequately controlled postoperative pain is associated with atelectasis, pulmonary infection and venous thrombosis. Furthermore the physiological and psychological implication of poorly controlled pain may contribute to higher opioid usage and the development of short term side effects and increased likelihood of chronic pain. Thoracic epidural catheter has historically been the primary choice for initial pain management, using (at VMMC) an infusion of Bupivacaine 0.05%, and Hydromorphone 10-microgram/cc at 8 ml/h. Appropriate positioning of the epidural catheter can be verified with an epidurogram before leaving the operating room. The catheter is repositioned or replaced when indicated, to ensure a functioning pain treatment system. Epidural pain catheters can be associated with postoperative hypotension which is a liability after esophagectomies.Thoracic paravertebral pain catheter placed by the surgeon under direct vision is a previously well-described alternative to epidural catheter forpostoperative pain management PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5IaWRhPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48UmVj

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ADDIN EN.CITE.DATA (1-4). These catheters have been demonstrated to be equivalent to epidurals in previous studies but not in comparisons where the epidural position has been verified with epidurography. Perioperative fluids are administered to treat hypotension during surgery caused by central anesthetic agents, and epidural induced vascular dilatation, bleeding and insensible losses. The use of vasopressors has been identified as a potential risk for decreased gastric conduit circulationPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UaGVvZG9yb3U8L0F1dGhvcj48WWVhcj4yMDA4PC9ZZWFy

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ADDIN EN.CITE.DATA (5), but studies have shown that intravenous adrenaline, phenylephrine, or ephedrine can increase mean arterial blood pressure (MAP) and maintain conduit perfusion as long as the patient is otherwise hemodynamically stable PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5KYW5zZW48L0F1dGhvcj48WWVhcj4yMDE4PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (6-9). Fluid overload can threaten anastomotic integrity and confer increased risk for postoperative morbidity and mortality PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYWxob3RyYTwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+

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ADDIN EN.CITE.DATA (10-12). The introduction of Enhanced Recovery after Surgery (ERAS) pathways and centralization of care to high volume centers has been shown to reduce postoperative morbidity PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXJrYXI8L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS

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ADDIN EN.CITE.DATA (13-16). The focus of perioperative management should be to optimize the patient’s physiology in order to facilitate patients’ postoperative recovery. ERAS guidelines provide a framework within which therapeutic goals can be set and clear strategies enacted where there is the potential for unintended deviation from the expected course. Several central components of ERAS pathways including restrictive fluid protocols, epidural analgesia, and early mobilization, whilst intended to advance recovery may also contribute to perioperative hypotension. A balanced approach to perioperative care should include adherence to ERAS principals PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Mb3c8L0F1dGhvcj48WWVhcj4yMDE4PC9ZZWFyPjxSZWNO

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ADDIN EN.CITE.DATA (7, 17). Insertion of a thoracic epidural catheter, whilst routinely performed in patients undergoing elective thoracic surgery, may be complicated by procedural and patient specific factors that can lead to uncertainty regarding catheter placement. Specifically, use of indirect anatomical assessments and reliance upon subtle sensory cues can, in certain situations, make confirmation of a properly functioning epidural catheter challenging even for experienced clinicians. Furthermore, sensory testing and patient reported pain scores, whilst helpful in determining sensory perception, do not provide objective evidence of correct epidural catheter placement. These assessments are made even more challenging in patients taking chronic opioids. In acknowledgement of these challenges, reported rates of epidural ‘failure’ typically vary in the range of 12-40%. There is a clinical need to improve postoperative pain treatment thoracic surgery specifically to reduce the risk for postoperative hypotension and improve the recovery of the patients. Over the past 12 years, it has been an institutionally mandated practice at Virginia Mason to perform a single (anteroposterior) chest x-ray before leaving the operating room. It is routine practice to also perform a postoperative epidurogram before leaving the operating room following preoperative epidural placement. Images are typically interpreted by either the anesthesiologist ordering the test or, in a minority of cases, by a faculty member with specific interest and experience in this technique. Prior assessment of reliability between reviewers was found to be high (κ 0.87, 95%CI 0.77-0.98). Furthermore, a retrospective review of patients undergoing esophagectomy at Virginia Mason determined that forty-eight (24.4%: 41♂; 65±11yrs) of 197 patients who underwent esophagectomy 2012-2018 had a postoperative epidurogram. In 11 (23%) of these patients, epidurogram findings led to a direct change in patient management, prompting either: removal/replacement of an incorrectly sited catheter (n=9), or partial withdrawal of a catheter associated with unilateral contrast distribution (n=2). Median postoperative day-1 pain scores were 2.5 (IQR,2-5) in this group. Of the remaining 37 patients in whom correct epidural placement was confirmed by epidurogram, this information endorsed the clinical decision to modify analgesic regimen in 8 (17%) patients with inadequate postoperative pain control. Incorrect epidural placement that was rescued was not associated with longer ICU/hospital stay or postoperative morbidity (P>0.05). Critically, the selective application of epidurograms has not been associated with any adverse events or patient morbidity. These findings confirm that an epidurogram is safe and can directly contribute to patient care in up to 40% of cases.There is currently an ongoing prospective observational study (IRB18-014) aimed to determine whether performing an epidurogram in patients after thoracotomy may facilitate early detection of miss-sited epidural catheters, provide an understanding of the accuracy of current clinical parameters in predicting correct catheter placement, and highlight potential barriers to implementation of this technique in clinics outside of VMMC so as to optimize immediate post-operative pain control and patient care. The aim of this study is to determine if thoracic paravertebral pain catheters are a non-inferior alternative in postoperative pain control after thoracic surgery, and if they induce less hypotension compared to thoracic epidural pain catheter, when the correct placement of the catheters is verified with postoperative contrast radiography.RESEARCH DESIGN AND METHODSStudy design Randomized clinical non-inferiority trial.Sample sizePower is set at 80% and significance level at 5%, with a non-inferiority design accepting no more than 0.5 points difference between the groups in average postoperative pain score in mobilization for the first 48 hours, and using 0.8 for standard deviation of postoperative analogue pain score, 32 patients are required in each treatment group. 1. Open surgery with epidural pain catheter (n=32). 2. Open surgery with paravertebral pain catheter (n=32). 3. Minimally invasive surgery with epidural pain catheter (n=32). 4. Minimally invasive surgery with paravertebral pain catheter (n=32). In total 128 patients (64 open and 64 minimally invasive surgery) will be randomized in separate blocks 1:1 to epidural or paravertebral pain catheters. The randomization of pain catheters will be 1:1 within each surgical group using computerized randomization in Redcap at the time of preoperative evaluation.Inclusion criteriaMale or non-pregnant female, age 18 or greaterPatient undergoing elective thoracic surgery with open or minimally invasive technique.Surgery with indication for an epidural or paravertebral pain catheter.Per investigator judgment, patient able to conform to anesthesia management protocol.Patient able and willing to provide written informed consent.Exclusion criteriaPatient undergoing emergency surgery.Patients undergoing surgery that does not involve thoracic dissection.Patients with preoperative requirement for receiving additional invasive interventions for postoperative pain control (e.g. paraspinal, intercostal or transverse abdominis plane blocks) at the time of surgery.Patients in whom epidural or paravertebral catheter placement is contraindicated.Patients with a confirmed allergy to Iopamidol or other radiological contrast agents. History of chronic pain with anticipation of difficult postoperative pain control, or history of chronic opioid use (defined as > 20 mg oral morphine equivalent per day on average in the past 4 weeks) with anticipation of difficult postoperative pain control per investigator judgment.Prior enrollment into this study.ExposureThoracic epidural pain catheter or thoracic paravertebral pain catheter for postoperative pain treatment. Subjects who are excluded from the trial at the time of surgery prior to receipt of the randomized catheter will be considered screen failures and will be replaced. Any subject who received the randomized catheter will be considered enrolled and will not be replaced. All included patients will be put on the acute pain service list for postoperative pain management. Standard of care ordersets for postoperative pain management with epidural and paravertebral pain catheters will be applied depending on the patients’ allocation. OutcomesPrimary outcome will be mean postoperative visual analogue pain score (VAS) 0-10 measured at mobilization 22-26 hours, and 46-50 hours after surgery (ordinal score 0-10). Secondary outcomes includes: VAS score during rest and cough measured at 22-26 hours, and 46-50 hours after surgery (ordinal score 0-10), postoperative hypotension with mean arterial pressure <70 mmHg for more than 15 minutes during the first 48 hours after surgery (ordinal, number of events), postoperative total need for intravenous fluid treatment for the first 48 postoperative hours (continuous in milliliters), length of hospital stay (continuous in days), patient reported satisfaction for the first 48 hours (recorded once at 22-26 hours and once at 46-50 hours after surgery) using the Brief Pain Inventory questionnaire (continuous score), overall patient reported satisfaction measured with the EORTC IN-PATSAT32 at the day of discharge, total dose of postoperative opioids reported in morphine equivalents (continuous in milligrams) for the first 48 hours after surgery, and need for change in postoperative pain treatment regimen (binary yes/no).Confirmation of catheter positionIn line with current standard practice at Virginia Mason Medical Center, an epidurogram is performed in all thoracic surgery patients receiving an epidural pain catheter before leaving the operation room. The confirmation of paravertebral pain catheters will be performed with the same technique using the postoperative radiography with contrast injection in the pain catheter before leaving the operation room.Method for performing epidurogram and paravertebral contrast radiographyUsing an aseptic technique, 5ml of sterile preservative free iopamidol 61 % (Isovue-M-300, Bracco Imaging, Monroe Township, USA) will be injected into the epidural/paravertebral catheter. A single anteroposterior x-ray image of thoracic spine will be obtained immediately following contrast injection.Interpretation of radiography Radiographs will be interpreted by the primary anesthesiology team in conjunction with a senior member of the anesthesiology faculty with interpretation expertise and documented in Cerner under the epidurogram search term. Images will be assessed for: (i) evidence of contrast in epidural/paravertebral space; (ii) extent of vertical contrast spread (number of vertebral levels above and below catheter tip), and; (iii) lateral spread of contrast (midline, right or left). As per standard of care, the patients will be followed by the acute pain service post-operatively, with a daily documentation of pain assessments in rest and at mobilization. Outcome of epidurogram interpretationIt will remain the responsibility of the anesthesiology pain team to determine the requirement for clinical intervention and rescue pain therapies based on patient assessments, radiological evaluation of the paravertebral catheter, and radiography findings. When indicated, the pain treatment may be modified using any available therapy (e.g., patients with epidural may receive opioid infusion; patients with paravertebral catheter may receive an epidural, etc.). If the pain catheter is removed the continued management will be at the discretion of the anesthesiologist in charge. Data collectionData will be principally derived from the standardized clinical notes recorded by the anesthesiology team during the perioperative period. This data will include: Type of surgery, details of epidural or paravertebral catheter placement; result and interpretation of radiological verification; intervention(s) resultant from performing radiology; details regarding patient analgesia requirement in the first 24 hours following surgery; postoperative morbidity including:Pulmonary? complications:Pneumonia, definition according to American Thoracic Society and Infectious Diseases Society of America: presence of a new or progressive radiographic infiltrate?plus?at?least?two of three?following clinical features.1. Fever greater than 38°C?2. Leukocytosis or leukopenia3. Purulent secretionsPleural effusion requiring additional drainage procedure?.Pneumothorax requiring treatment?.Atelectasis mucous plugging requiring bronchoscopy.?Respiratory failure requiring reintubation?.Acute respiratory distress syndrome according to the Berlin Definition.Acute aspiration?.Tracheobronchial injury requiring chest tube maintenance for air leak for >10 d postoperatively. Cardiac? complications:Cardiac arrest requiring CPR?.Myocardial infarction (Definition: World Health Organization) Atrial fibrillation requiring treatment.?Ventricular dysrhythmia requiring treatment.?Congestive heart failure requiring treatment?.Pericarditis requiring treatment Gastrointestinal? complications:Esophagoenteric leak from anastomosis, staple line, or localized conduit necrosis according to the ECCG definitions.Conduit necrosis/failure according to the ECCG definitions.Ileus defined as small bowel dysfunction preventing or delaying enteral feeding?.Small bowel obstruction.?Feeding J-tube complication?.Pyloromyotomy/pyloroplasty complication?.Clostridium Difficile Infection.?Gastrointestinal bleeding requiring intervention or transfusion?.Delayed conduit emptying requiring intervention or delaying discharge or requiring maintenance of NG drainage >7 d postoperatively. Pancreatitis?.Liver dysfunction. Urologic complications:?Acute renal insufficiency (defined as doubling of baseline creatinine)?Acute renal failure requiring dialysis?.Urinary tract infection?.Urinary retention requiring reinsertion of urinary catheter, delaying discharge, or discharge with urinary catheter. Thromboembolic complications: ?Deep venous thrombosis. Pulmonary embolus?.Stroke (CVA)?.Peripheral thrombophlebitis. Neurologic/psychiatric? complications:Recurrent nerve injury according to the ECCG definition.Acute delirium (Definition: Diagnostic and Statistical Manual of Mental Disorders, 5th ed)Delirium tremens.Infectious comlications:?Wound infection requiring opening wound or antibiotics Central IV line infection requiring removal or antibiotics. Intrathoracic/intra-abdominal abscess?.Generalized sepsis, definition: Center for Disease Control and Prevention.Other infections requiring antibiotics.Wound complications:?Thoracic wound dehiscence.?Acute abdominal wall dehiscence/hernia Acute diaphragmatic hernia.Other complications:?Chyle leak defined according to the ECCG. ?Reoperation for reasons other than bleeding, anastomotic leak, or conduit necrosis?Multiple organ dysfunction syndrome (Definition: American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee).Nausea and vomiting postoperatively.Pruritus postoperatively.All complications/adverse events occurring within 30 days of surgery or during the in-hospital stay after surgery will be included. All complications will be scored according to the Clavien-Dindo score. Length of ICU and hospital stay. Instances of postoperative hypotension with mean arterial pressure <70 mmHg for more than 15 minutes and the postoperative total need for intravenous fluid treatment for the first 48 postoperative hours will be ascertained from Cerner. Patients will complete the VAS scale and Brief Pain Inventory (BPI) 2 times during the first 48 hours following surgery: at mobilization, at rest, and at cough, at 24 hour (=/-2hours) postoperative time point and again at mobilization, at rest, and at cough, after 48 hours (=/-2hours) postoperatively. The subject will complete the EORTC IN-PATSAT32 questionnaire approximately 48 hours after surgery. Adverse events judged to be related to study procedures will also be captured and included in the data analysis. The VAS and BPI scores and information about adverse events and postoperative hypotension will be collected using a study data collection sheet (attachment 1). Clinical data during the entire length of stay will be collected in accordance with the Institutional database for outcomes of the surgical management of esophageal disease study (IRB18-076).Data storagePatient data will be stored in a password protected Redcap database that will be stored securely within a password protected networked computer within the department of Thoracic Surgery at Virginia Mason. Once data analysis is complete, the data obtained in this study will be added to the IRB approved institutional database (IRB18-076). All research specific paper records associated with this protocol will be securely archived and stored for a minimum of 10 years after the study closes. The data will be stored long-term under IRB18-076 and any archival will follow as indicated in that protocol.Data analysisData will be analyzed using StataIC version 14 (Copyright 1985-2015 StataCorp LLC, Texas 77845 USA). Data will be analyzed according to the intention to treat principle. Categorical data will be compared using the chi-square test or Fisher's exact test in case of small cell counts. Continuous data will be compared using the Mann-Whitney-U test (non-parametric variables) or Student’s T-test (parametric variables). Linear regression models will be used to compare means of continuous variables and logistic regression models for binary outcomes. Quality AssuranceThe Clinical Research Program will assess the risk of this trial and will devise and implement an internal monitoring and/or auditing plan for this trial. This plan will be revised as necessary during the life of the trial based upon a variety of factors, including but not limited to: protocol amendments, staff turnover, enrollment metrics, and compliance issues noted. PROTECTION OF HUMAN SUBJECTSRisks to human subjectsThis is a randomized controlled trial that will rely on the collection and analysis of prospectively recorded patient data. Patients who are potentially eligible for inclusion in this study will be known both to the anesthetic and surgical team responsible for their perioperative care.Prior to participation in the study, all patients will be given written and oral information about the trial. Written informed consent will be obtained from all participants prior to any study procedures.The primary risk that this study poses to patients is that of a suboptimal postoperative pain treatment. The pain treatment of all included patients will be closely monitored, and if the pain control is unsatisfactory additional treatment will be given at the discretion of the anesthesiologist or surgeon responsible for the patient’s care at any time, without regard to the study. Additional pain treatment options include everything that is available to patients outside of the trial. A secondary risk is a breach of confidentiality. Details of patient care including anesthetic management are stored within patients’ electronic medical records (Cerner) as is standard practice. Study data will be gathered on a data collection sheet and stored in a secure password protected Redcap database during the course of this study. Data collection sheets will be saved in a locked cabinet at the institution. Only data that is directly related to the study question will be extracted from patient electronic medical record and assimilated within the database. A list of collected variables is enclosed (Attachment 2) No patient identifiable data will be shared outside of the patient’s care team except as necessary for regulatory/institutional reviews and/or audits.No extra financial costs will be passed either to Virginia Mason Medical Center or to patients and their insurance provider.Potential benefits of the proposed research to the subjects and othersThe hypothesis is that thoracic paravertebral pain catheters are non-inferior for pain management to the standard thoracic epidural catheter used today and may be superior in terms of overall recovery by reducing the instance of intraoperative hypotension. As such, it is possible that the patients randomized to thoracic paravertebral catheters may receive a better postoperative recovery because of the trial. Identifying and reporting adverse events: reporting proceduresAll adverse events (serious or non-serious) that are related to the pain catheters or other study activities will be recorded and analyzed. Postoperative complications will be captured from Cerner according to the study protocol (see above).Adverse events that are associated with the pain catheter or study activity will be noted daily on all patient datasheets (see attachment CRF).Analogue pain score, pain management details, and hypotension episodes will also be reported on the patient datasheet (see attachment CRF).Depending on the nature of the event, the reporting procedures below should be followed. Any questions concerning adverse event reporting should be directed to the Principal Investigator. Non serious adverse eventsAll unexpected non-serious adverse events which are related to this study should be recorded. Serious adverse eventsAll serious adverse events related to study procedures will be considered unexpected and thus will be reported. A report including all pertinent details related to a serious adverse event (including but not limited to: start date, stop date, thorough description of the event, treatment, and outcome) should be reported to the local Principal Investigator within 3 days of occurrence. Additionally, all such serious adverse events will be reported to the IRB. Contact details for reporting SAEsDr Donald Low MDDonald.Low@Tel: (206) 223-6164 (Mon to Fri 09.00 – 17.00)Dr Neil Hanson MDNeil.Hanson@ Tel: (206) 559-0106 (Mon to Fri 09.00 – 17.00)Dr Sara Nikravan MDSara.Nikravan@ Tel: (206) 314-1483 (Mon to Fri 09.00 – 17.00)Dr. Fredrik KlevebroFredrik.Klevebro@ Tel: (206) 223-6818 (Mon to Fri 09.00 – 17.00)References ADDIN EN.REFLIST 1.Hida K, Murata H, Sakai A, Ogami K, Maekawa T, Hara T. [Perioperative Pain Management of Minimally Invasive Esophagectomy with Bilateral Continuous Thoracic Paravertebral Block]. Masui The Japanese journal of anesthesiology. 2016;65(2):119-24.2.Richardson J, Sabanathan S, Jones J, Shah RD, Cheema S, Mearns AJ. A prospective, randomized comparison of preoperative and continuous balanced epidural or paravertebral bupivacaine on post-thoracotomy pain, pulmonary function and stress responses. British journal of anaesthesia. 1999;83(3):387-92.3.Marret E, Bazelly B, Taylor G, Lembert N, Deleuze A, Mazoit JX, et al. Paravertebral block with ropivacaine 0.5% versus systemic analgesia for pain relief after thoracotomy. The Annals of thoracic surgery. 2005;79(6):2109-13.4.Eason MJ, Wyatt R. Paravertebral thoracic block-a reappraisal. Anaesthesia. 1979;34(7):638-42.5.Theodorou D, Drimousis PG, Larentzakis A, Papalois A, Toutouzas KG, Katsaragakis S. The effects of vasopressors on perfusion of gastric graft after esophagectomy. An experimental study. Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract. 2008;12(9):1497-501.6.Jansen SM, de Bruin DM, van Berge Henegouwen MI, Bloemen PR, Strackee SD, Veelo DP, et al. Effect of ephedrine on gastric conduit perfusion measured by laser speckle contrast imaging after esophagectomy: a prospective in vivo cohort study. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus / ISDE. 2018.7.Al-Rawi OY, Pennefather SH, Page RD, Dave I, Russell GN. The effect of thoracic epidural bupivacaine and an intravenous adrenaline infusion on gastric tube blood flow during esophagectomy. Anesth Analg. 2008;106(3):884-7, table of contents.8.Pathak D, Pennefather SH, Russell GN, Al Rawi O, Dave IC, Gilby S, et al. Phenylephrine infusion improves blood flow to the stomach during oesophagectomy in the presence of a thoracic epidural analgesia. Eur J Cardiothorac Surg. 2013;44(1):130-3.9.Holte K, Foss NB, Svensen C, Lund C, Madsen JL, Kehlet H. Epidural anesthesia, hypotension, and changes in intravascular volume. Anesthesiology. 2004;100(2):281-6.10.Malhotra K, Axisa B. Low plasma albumin linked to fluid overload in postoperative epidural patients. Annals of the Royal College of Surgeons of England. 2009;91(8):703-7.11.Moller AM, Pedersen T, Svendsen PE, Engquist A. Perioperative risk factors in elective pneumonectomy: the impact of excess fluid balance. Eur J Anaesthesiol. 2002;19(1):57-62.12.Marjanovic G, Villain C, Juettner E, zur Hausen A, Hoeppner J, Hopt UT, et al. Impact of different crystalloid volume regimes on intestinal anastomotic stability. Annals of surgery. 2009;249(2):181-5.13.Markar SR, Karthikesalingam A, Low DE. Enhanced recovery pathways lead to an improvement in postoperative outcomes following esophagectomy: systematic review and pooled analysis. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus / ISDE. 2015;28(5):468-75.14.Feldheiser A, Aziz O, Baldini G, Cox BP, Fearon KC, Feldman LS, et al. Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 2: consensus statement for anaesthesia practice. Acta Anaesthesiol Scand. 2016;60(3):289-334.15.Low DE, Allum W, De Manzoni G, Ferri L, Immanuel A, Kuppusamy M, et al. Guidelines for Perioperative Care in Esophagectomy: Enhanced Recovery After Surgery (ERAS((R))) Society Recommendations. World journal of surgery. 2018.16.Findlay JM, Gillies RS, Millo J, Sgromo B, Marshall RE, Maynard ND. Enhanced recovery for esophagectomy: a systematic review and evidence-based guidelines. Annals of surgery. 2014;259(3):413-31.17.Klijn E, Niehof S, de Jonge J, Gommers D, Ince C, van Bommel J. The effect of perfusion pressure on gastric tissue blood flow in an experimental gastric tube model. Anesth Analg. 2010;110(2):541-6. ................
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