Kelly Byrne

Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery

Background Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects. Methods In a trial with a 2‐by‐2 factorial design, we randomly assigned patients who were scheduled to undergo coronary‐artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. Results Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P=0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P=0.001), and seizures occurred in 0.7% and 0.1%, respectively (P=0.002 by Fishers exact test). Conclusions Among patients undergoing coronary‐artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.)

Restrictive or Liberal Red-Cell Transfusion for Cardiac Surgery

BACKGROUND The effect of a restrictive versus liberal red‐cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. METHODS In this multicenter, open‐label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red‐cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red‐cell transfusion threshold (transfuse if hemoglobin level was <9.5 g per deciliter in the operating room or intensive care unit [ICU] or was <8.5 g per deciliter in the non‐ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new‐onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red‐cell transfusion and other clinical outcomes. RESULTS The primary outcome occurred in 11.4% of the patients in the restrictive‐threshold group, as compared with 12.5% of those in the liberal‐threshold group (absolute risk difference, ‐1.11 percentage points; 95% confidence interval [CI], ‐2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive‐threshold group and 3.6% in the liberal‐threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red‐cell transfusion occurred in 52.3% of the patients in the restrictive‐threshold group, as compared with 72.6% of those in the liberal‐threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between‐group differences with regard to the other secondary outcomes. CONCLUSIONS In patients undergoing cardiac surgery who were at moderate‐to‐high risk for death, a restrictive strategy regarding red‐cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new‐onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898.)

Survey of phantom limb pain, phantom sensation and stump pain in Cambodian and New Zealand amputees.

OBJECTIVE The primary objective of this study is to compare the prevalence of phantom limb pain in New Zealand and Cambodian amputees and to assess the demographics of a sample of amputees from these two countries. DESIGN All participants were interviewed using a 12-question survey that covered demographic data and reason for amputation and assessed the presence of phantom limb sensation, phantom limb pain, and stump pain. Amputees attending an artificial limb center in Cambodia were approached and interviewed in person. New Zealand amputees attending the Waikato artificial limb center were randomly selected and interviewed by phone. RESULTS There was no statistically significant difference in phantom limb sensation, phantom limb pain, or stump pain between the two groups. There was a much higher unemployment rate in the Cambodian amputees. There were no other statistically significant differences between the groups CONCLUSION Despite very different environments, there was no difference in the phantom limb pain between the groups. One possible explanation is that the severity of neurological injury associated with amputation overrides all the other risk factors that influence the development of other chronic pain syndromes.

Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery

Background We reported previously that, in patients undergoing cardiac surgery who were at moderate‐to‐high risk for death, a restrictive transfusion strategy was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new‐onset renal failure with dialysis by hospital discharge or 28 days after surgery, whichever came first. We now report the clinical outcomes at 6 months after surgery. Methods We randomly assigned 5243 adults undergoing cardiac surgery to a restrictive red‐cell transfusion strategy (transfusion if the hemoglobin concentration was <7.5 g per deciliter intraoperatively or postoperatively) or a liberal red‐cell transfusion strategy (transfusion if the hemoglobin concentration was <9.5 g per deciliter intraoperatively or postoperatively when the patient was in the intensive care unit [ICU] or was <8.5 g per deciliter when the patient was in the non‐ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new‐onset renal failure with dialysis occurring within 6 months after the initial surgery. An expanded secondary composite outcome included all the components of the primary outcome as well as emergency department visit, hospital readmission, or coronary revascularization occurring within 6 months after the index surgery. The secondary outcomes included the individual components of the two composite outcomes. Results At 6 months after surgery, the primary composite outcome had occurred in 402 of 2317 patients (17.4%) in the restrictive‐threshold group and in 402 of 2347 patients (17.1%) in the liberal‐threshold group (absolute risk difference before rounding, 0.22 percentage points; 95% confidence interval [CI], ‐1.95 to 2.39; odds ratio, 1.02; 95% CI, 0.87 to 1.18; P=0.006 for noninferiority). Mortality was 6.2% in the restrictive‐threshold group and 6.4% in the liberal‐threshold group (odds ratio, 0.95; 95% CI, 0.75 to 1.21). There were no significant between‐group differences in the secondary outcomes. Conclusions In patients undergoing cardiac surgery who were at moderate‐to‐high risk for death, a restrictive strategy for red‐cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new‐onset renal failure with dialysis at 6 months after surgery. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898.)

Tranexamic Acid in Coronary Artery Surgery: One-Year Results of the ATACAS Trial

Background Tranexamic acid reduces blood loss and transfusion requirements in cardiac surgery but may increase the risk of coronary graft thrombosis. We previously reported the 30‐day results of a trial evaluating tranexamic acid for coronary artery surgery. Here we report the 1‐year clinical outcomes. Methods Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary 1‐year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score of less than 8. Secondary outcomes included a composite of myocardial infarction, stroke, and death from any cause through to 1 year after surgery. Results The rate of death or disability at 1 year was 3.8% in the tranexamic acid group and 4.4% in the placebo group (relative risk, 0.85; 95% confidence interval, 0.64‐1.13; P = .27), and this did not significantly differ according to aspirin exposure at the time of surgery (interaction P = .073). The composite rate of myocardial infarction, stroke, and death up to 1 year after surgery was 14.3% in the tranexamic acid group and 16.4% in the placebo group (relative risk, 0.87; 95% CI, 0.76‐1.00; P = .053). Conclusions In this trial of patients having coronary artery surgery, tranexamic acid did not affect death or severe disability through to 1 year after surgery. Further work should be done to explore possible beneficial effects on late cardiovascular events.

History of Cardiac Anesthesia in New Zealand

New Zealand has a long and proud history of innovation in cardiac surgery and anesthesia. There have been a number of prominent men and women who have contributed to the development of cardiac anesthesia in New Zealand. There are numerous ongoing challenges in providing cardiac anesthetic services to the population of New Zealand.

Medical Legal Aspects of Regional Anesthesia: Legal Perspective

Understanding of regional anesthesia malpractice claims from a lawyer’s perspective is helpful in appreciating the legal process involved, including requirements for record-keeping, documentation of consent, and cases of practicing outside of guidelines. Legal systems and definitions of malpractice vary around the world; however, for most jurisdictions, a successful claim requires that patient be able to establish that the anesthesiologist owed them a duty of care and that this duty was breached, resulting in injury. Important legal issues can arise from lack of documentation of procedures, incomplete records, absence of or incomplete patient consent, issues with handover of care, and failure to adhere to recommended guidelines and practice standards.

Transfusion Requirements in Cardiac Surgery III (TRICS III): Study Design of a Randomized Controlled Trial

OBJECTIVES To determine if a restrictive transfusion threshold is noninferior to a higher threshold as measured by a composite outcome of mortality and serious morbidity. DESIGN Transfusion Requirements in Cardiac Surgery (TRICS) III was a multicenter, international, open-label randomized controlled trial of two commonly used transfusion strategies in patients having cardiac surgery using a noninferiority trial design (ClinicalTrials.gov number, NCT02042898). SETTING Eligible patients were randomized prior to surgery in a 1:1 ratio. PARTICIPANTS Potential participants were 18 years or older undergoing planned cardiac surgery using cardiopulmonary bypass (CPB) with a preoperative European System for Cardiac Operative Risk Evaluation (EuroSCORE I) of 6 or more. INTERVENTIONS Five thousand patients; those allocated to a restrictive transfusion group received a red blood cell (RBC) transfusion if the hemoglobin concentration (Hb) was less than 7.5 g/dL intraoperatively and/or postoperatively. Patients allocated to a liberal transfusion strategy received RBC transfusion if the Hb was less than 9.5 g/dL intraoperatively or postoperatively in the intensive care unit or less than 8.5 g/dL on the ward. MEASUREMENTS AND MAIN RESULTS The primary outcome was a composite of all-cause mortality, myocardial infarction, stroke, or new onset renal dysfunction requiring dialysis at hospital discharge or day 28, whichever comes first. The primary outcome was analyzed as a per-protocol analysis. The trial monitored adherence closely as adherence to the transfusion triggers is important in ensuring that measured outcomes reflect the transfusion strategy. CONCLUSION By randomizing prior to surgery, the TRICS III trial captured the most acute reduction in hemoglobin during cardiopulmonary bypass.

Managing Postoperative Analgesic Failure: Tramadol Versus Morphine for Refractory Pain in the Post-Operative Recovery Unit

Objective. This study aimed to discover whether co-analgesia with tramadol or additional morphine was more effective for patients who still had severe pain despite being given 10 mg intravenous morphine in the post-anesthesia care unit (PACU). Methods. All eligible patients were consented and recruited to the trial pre-operatively, but only a small subgroup – whose pain was not successfully controlled (pain score 6/10 or more) after receiving 10 mg of morphine in the PACU—were then randomized to enter the trial and receive, in a double blinded fashion, the analgesic study drug; which consisted of either a further 10 mg of morphine, or 100 mg of tramadol, titrated intravenously to control their pain. The groups were compared as to: the time to readiness for discharge, the patient’s pain scores over time, and the presence of side effects. Results. There was no statistically significant difference in any of the outcomes measured. The time to readiness for discharge from PACU was 119 minutes in the morphine group and 120 minutes in the tramadol group. However in approximately half the cases who entered the trial (i.e., where pain had not been controlled with the pre-enrollment baseline 10 mg of morphine in PACU) neither a further 10 mg of morphine nor 100 mg of tramadol effectively relieved the patient’s pain. Conclusions. We found no difference between additional morphine and co-analgesia with tramadol in this study. Patients who don’t respond to reasonable doses of opioids in PACU are very likely to be unresponsive to further opioids, and other non-opioid analgesic techniques (such as regional anesthesia) should be considered early in this group of patients.

Pediatric Electrical Nerve Stimulation

Nerve stimulation has revolutionized the ability to perform peripheral nerve blocks in the pediatric population. This technique provides a method of localizing nerves with an objective end point that does not rely on the patient being awake. As the majority of pediatric regional blocks are carried out under general anesthesia or heavy sedation, nerve stimulation has proven to be a powerful tool in this field. Nerve stimulation uses electrical impulses to induce a flow of ions through the neuronal cell membrane to “excite” the nerve. This leads to a subsequent depolarization of the nerve and the generation of an action potential. The action potential eventually results in either muscle contraction or paresthesia, depending on the nerve distribution and the type of nerve – motor or sensory. This chapter provides an overview of the use of nerve stimulation, including the electrophysiological principles underlying the procedure and the application of the electrical epidural stimulation test for placing epidural catheters. By the end of the chapter, the reader will have the background knowledge necessary to understand and apply nerve stimulation during peripheral and neuraxial regional anesthesia.