Examination of psychological risk factors for chronic pain following cardiac surgery: protocol for a prospective observational study

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: Approximately 400 000 Americans and 36 000 Canadians undergo cardiac surgery annually, and up to 56% will develop chronic postsurgical pain (CPSP). The primary aim of this study is to explore the association of pain-related beliefs and gender-based pain expectations on the development of CPSP. Secondary goals are to: (A) explore risk factors for poor functional status and patient-level cost of illness from a societal perspective up to 12 months following cardiac surgery; and (B) determine the impact of CPSP on quality-adjusted life years (QALYs) borne by cardiac surgery, in addition to the incremental cost for one additional QALY gained, among those who develop CPSP compared with those who do not. METHODS AND ANALYSES: In this prospective cohort study, 1250 adults undergoing cardiac surgery, including coronary artery bypass grafting and open-heart procedures, will be recruited over a 3-year period. Putative risk factors for CPSP will be captured prior to surgery, at postoperative day 3 (in hospital) and day 30 (at home). Outcome data will be collected via telephone interview at 6-month and 12-month follow-up. We will employ generalised estimating equations to model the primary (CPSP) and secondary outcomes (function and cost) while adjusting for prespecified model covariates. QALYs will be estimated by converting data from the Short Form-12 (version 2) to a utility score. ETHICS AND DISSEMINATION: This protocol has been approved by the responsible bodies at each of the hospital sites, and study enrolment began May 2015. We will disseminate our results through CardiacPain.Net, a web-based knowledge dissemination platform, presentation at international conferences and publications in scientific journals. TRIAL REGISTRATION NUMBER: NCT01842568

Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3) : a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery

Altres ajuts: Canadian Institutes of Health Research (CIHR, FDN-143302); General Research Fund (14104419), Research Grant Council, Hong Kong SAR, China; National Health and Medical Research Council, Funding Schemes (NHMRC Project Grant 1162362), Australia; McMaster University Department of Medicine Career Research Award and a Physicians' Services Incorporated (PSI) Foundation Mid-Career Clinical Research Award.Background: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. Methods: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. Discussion: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. Trial registration: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018

Aspirin and clonidine in non-cardiac surgery: acute kidney injury substudy protocol of the Perioperative Ischaemic Evaluation (POISE) 2 randomised controlled trial

IntroductionPerioperative Ischaemic Evaluation-2 (POISE-2) is an international 2×2 factorial randomised controlled trial of low-dose aspirin versus placebo and low-dose clonidine versus placebo in patients who undergo non-cardiac surgery. Perioperative aspirin (and possibly clonidine) may reduce the risk of postoperative acute kidney injury (AKI).Methods and analysisAfter receipt of grant funding, serial postoperative serum creatinine measurements began to be recorded in consecutive patients enrolled at substudy participating centres. With respect to the study schedule, the last of over 6500 substudy patients from 82 centres in 21 countries were randomised in December 2013. The authors will use logistic regression to estimate the adjusted OR of AKI following surgery (compared with the preoperative serum creatinine value, a postoperative increase ≥26.5 μmol/L in the 2 days following surgery or an increase of ≥50% in the 7 days following surgery) comparing each intervention to placebo, and will report the adjusted relative risk reduction. Alternate definitions of AKI will also be considered, as will the outcome of AKI in subgroups defined by the presence of preoperative chronic kidney disease and preoperative chronic aspirin use. At the time of randomisation, a subpopulation agreed to a single measurement of serum creatinine between 3 and 12 months after surgery, and the authors will examine intervention effects on this outcome.Ethics and disseminationThe authors were competitively awarded a grant from the Canadian Institutes of Health Research for this POISE-2 AKI substudy. Ethics approval was obtained for additional kidney data collection in consecutive patients enrolled at participating centres, which first began for patients enrolled after January 2011. In patients who provided consent, the remaining longer term serum creatinine data will be collected throughout 2014. The results of this study will be reported no later than 2015.Clinical Trial Registration NumberNCT01082874

Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery

Background For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. Methods The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. Discussion Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. Trial registration ClinicalTrials.gov NCT03505723. Registered on 23 April 2018

Tetanus in developing countries: a case series and review

Purpose Few anesthesiologists have expertise in the diagnosis and treatment of tetanus, a disease that remains prevalent in developing countries. We report on a series of four cases of tetanus cases recently encountered in Rwanda. We review the clinical epidemiology, pathophysiology, diagnosis and the treatment of tetanus, and provide implications for anesthesiologists and critical care physicians. Clinical features We report four cases, two involving adults who were inadequately vaccinated and experienced injuries, and two involving neonates, both of whom underwent umbilical cord transection using unsterilized equipment. All patients required tracheal intubation, and were mechanically ventilated when equipment was available. One adult and one neonate succumbed to the disease. These cases highlight the difficulties of diagnosis and management of complicated diseases in the resource-challenged health care setting of developing countries. Conclusions The differential diagnosis of tetanus may be confusing, and survival depends on the rapidity of treatment with antitoxin, as well as adequate supportive care. High doses of sedatives and muscle relaxants, as well as prolonged mechanical ventilation, are usually necessary. Mortality remains high, usually resulting from late respiratory failure and cardiovascular collapse, associated with autonomic instability. Anesthesiologists and critical care physicians have an important role to play in the management of these patients. Increased involvement in humanitarian health organizations, immigration from developing countries, and emergence of high risk groups in developed countries will likely result in more exposure of anesthesiologists to the complexities of this disease. Résumé Objectif Très peu d’anesthésiologistes sont experts du diagnostic et du traitement du tétanos, une pathologie qui demeure prévalente dans les pays en voie de développement. Nous rapportons une série de quatre cas de tétanos survenus récemment au Rwanda. Nous passons en revue l’épidémiologie clinique, la physiopathologie, le diagnostic et le traitement du tétanos, et proposons des pistes intéressantes pour les anesthésiologistes et les médecins en soins critiques. Éléments cliniques Nous rapportons quatre cas dont deux impliquent des adultes mal vaccinés et qui ont subi des blessures, et deux concernent des nouveaux-nés, tous deux ayant subi une coupe transversale du cordon ombilical à l’aide d’instruments non stérilisés. Tous les patients ont nécessité une intubation trachéale et ont été ventilés mécaniquement lorsque le matériel était disponible. Ces cas soulignent les difficultés rencontrées lors du diagnostic et de la prise en charge de pathologies complexes dans le contexte des soins de santé manquant de ressources des pays en voie de développement. Conclusions Le diagnostic différentiel du tétanos peut porter à confusion, et la survie dépend de la rapidité du traitement avec de l’antitoxine ainsi que de soins d’accompagnement adaptés. En général, des doses élevées de sédatifs et de curares ainsi qu’une ventilation mécanique prolongée sont nécessaires. La mortalité demeure élevée, en général causée par une insuffisance respiratoire tardive et d’une défaillance cardiovasculaire combinées à une instabilité du système nerveux autonome. Les anesthésiologistes et les médecins en soins critiques ont un rôle important à jouer dans la prise en charge de ces patients. Un engagement accru dans les organisations sanitaires humanitaires, l’immigration des pays en voie de développement et l’émergence de groupes à haut risque dans les pays développés auront probablement pour résultat une plus grande exposition des anesthésiologistes aux éléments complexes de cette pathologie. The treatment of tetanus has many implications for anesthesiologists and critical care physicians, but most physicians in developed countries lack experience in dealing with such cases. With developed nations progressively more involved in the medical aid programs in developing countries, and with increased immigration and emerging risk groups in developed countries, physicians may increasingly be called upon to diagnose and treat this complex disease. Since 2006, the Canadian Anesthesiologists’ Society International Education Foundation (CAS-IEF), in conjunction with the American Society of Anesthesiologists, has made visiting faculty available as teachers for local anesthesiology residents and allied personnel in Rwanda. We recently participated in the CAS-IEF program in Rwanda and, during the month of February, 2008, encountered four new cases of tetanus presenting to the Intensive Care Unit of the Centre Hospitalier Universitaire de Kigali (CHUK), Rwanda’s largest public hospital. With approval of the institutional ethics committee, the Comité de Recherche Scientifique au CHUK, we present a summary of these cases and a review of the pathophysiology, treatment options, and anesthetic considerations of tetanus. Case 2 A 30-year-old farmer suffered a machete injury to his left index finger while working in the field. Ten days after injury, he first consulted with his local health clinic complaining of difficulty chewing and swallowing. The clinicians quickly decided to refer him to the district hospital, where, in turn, he was transferred to CHUK. On admission to CHUK, he was alert and oxygenating well on room air, but was manifesting all the typical signs of tetanus: generalized muscle spasms, opisthotonus, trismus, risus sardonicus facies, as well as nuchal rigidity, rigid abdomen, and a small healing wound on the index finger. The diagnosis of tetanus was made at this time, Day 1 of his illness, as was the diagnosis of malaria. The patient had no known history of having received a tetanus vaccination and was negative for antibodies to human immunodeficiency virus (HIV). Tetanus treatment included equine antitetanus immunoglobulin 3000 IU IM, metronidazole, diazepam 10 mg · h−1, oxygen by nasal cannula, and admission to the intensive care unit. Phenobarbital 50 mg iv qid was initiated for persistent paroxysms. Intravenous and nebulized atropine was administered for bronchial secretions. On Day 10 of his illness, pneumonia was diagnosed, based on a productive cough, fever of 38.5°C, and changes on chest radiograph. This was treated with ceftriaxone 2 g bid and gentamicin 80 mg bid. On Day 12 of the onset of his illness, the patient was intubated for respiratory distress in the face of persistent paroxysms of muscular spasm. Sedation and relaxation consisted of diazepam and sodium thiopentone 40 mg · h−1, morphine boluses, and vecuronium. The patient’s trachea was extubated on Day 18. He was discharged from hospital 24 days after admission, his only deficit being a flaccid left hand. He has returned to work with his community to promote awareness of the importance of tetanus vaccination. Case 3 A 10-week-old male infant was admitted to the intensive care unit at CHUK. The infant was born at term at home with a traditional birth attendant. The 19-year-old mother had only once been medically evaluated antenatally and had received one dose of tetanus vaccine. The umbilical cord had been cut with a previously used razor blade with no sterile precautions taken. No perinatal problems were noted. The family visited the district hospital shortly after the birth for a well-baby check-up; however, the infant’s vaccinations were delayed by 1 week due to refrigeration problems. Six weeks after birth, the infant developed episodic convulsions, spasms of his lower extremities, increased oral secretions, and cervical rigidity. The patient was not admitted to hospital until 1 week later, at which time he presented with generalized nonfebrile convulsions, muscular rigidity and spasms, transient apnea, and reduced reflexes. During a 3-week course in the district hospital for an undetermined illness, the infant received oxygen by mask, diazepam, and hydrocortisone. Lumbar puncture was performed during the course in hospital and reported as “blood-tinged.” Fever prompted a blood smear for malaria, which was positive, and antimalarial drugs were started. On Day 28 after onset of illness, the infant was eventually transferred late in his course to CHUK for suspected hemorrhagic meningitis, malaria, and possible tetanus. Upon admission to CHUK, he received his first dose of equine antitetanus immunoglobulin 500 IU im. The infant also received rectal diazepam 0.5 mg · kg−1, phenobarbital infusion 20 mg · d, dexamethasone, ceftriaxone, metronidazole, and oxygen by face mask. The infant was fed by gastric tube, and his trachea was intubated for airway protection following an episode of emesis after feeding. Ventilation was impaired due to muscle spasms and opisthotonus; however, there was no neonatal ventilator available at this time in the intensive care unit. The infant maintained spontaneous respiration via endotracheal tube for 2 days. His trachea was extubated on Day 30 after the convulsions and spasms had regressed. The infant was discharged 5 weeks after admission to CHUK and 9 weeks after onset of illness. Case 4 A male infant was diagnosed with tetanus only 4 days after birth. This infant was a second child born at home to an HIV negative mother who had only been seen once prenatally and had received a single dose of antitetanus immunoglobulin at 8 months’ gestation. After delivery, the umbilical cord was cut with unsterilized hairstyling scissors. At 4 days of age, the infant presented to a local hospital with generalized muscle spasms and was treated with diazepam and metronidazole. No antitetanus immunoglobulin was given. After making little improvement, he was transferred to CHUK on Day 10 after onset of illness. On arrival to CHUK on Day 10, the infant was opisthotonic; he also had trismus and excessive oral secretions. There was no bulging of fontanelles. The umbilical stump appeared infected. Intensive care admission and treatment included oxygen by face mask, intramuscular equine antitetanus immune globulin 500 IU im, cefotaxime, metronidazole, diazepam 0.4 mg · h, acetaminophen, magnesium sulfate, and calcium gluconate. Persistent muscle spasms necessitated increased diazepam doses as well as sodium thiopentone. He was nourished with nasogastric feeds. The infant remained agitated, and because he had difficulty managing his copious secretions, the infant was tracheally intubated but not mechanically ventilated. The intubation was difficult in the absence of muscle relaxants, which were avoided in order to maintain spontaneous respiration. Continued problems with endotracheal tube obstruction due to secretions necessitated tube replacement. Four days following his intubation, the infant became increasingly hypoxemic and subsequently bradycardic. Cardiac arrest ensued, and no epinephrine was available for resuscitation. The child expired following failed attempts at improving oxygenation

Perspectives, Perceptions and Experiences in Postoperative Pain Management in Developing Countries: A Focus Group Study Conducted in Rwanda

BACKGROUND: Access to postoperative acute pain treatment is an important component of perioperative care and is frequently managed by a multidisciplinary team of anesthesiologists, surgeons, pharmacists, technicians and nurses. In some developing countries, treatment modalities are often not performed due to scarce health care resources, knowledge deficiencies and cultural attitudes