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Summary Engaging patients—defined broadly as individuals with lived experience of a given condition, family members, caregivers, and the organisations that represent them—as partners in research is a priority for policymakers, funders, and the public. Nonetheless, formal efforts to engage patients are absent from most studies, and models to support meaningful patient engagement in clinical anaesthesia research have not been previously described. Here, we review our experience in developing and implementing a multifaceted patient engagement strategy within the Regional Versus General Anesthesia for Promoting Independence After Hip Fracture (REGAIN) surgery trial, an ongoing randomised trial comparing spinal vs general anaesthesia for hip fracture surgery in 1600 older adults across 45 hospitals in the USA and Canada. This strategy engaged patients and their representatives at both the level of overall trial oversight and at the level of individual recruiting sites. Activities spanned a continuum ranging from events designed to elicit patients' input on key decisions to longitudinal collaborations that empowered patients to actively participate in decision-making related to trial design and management. Engagement activities were highly acceptable to participants and led to concrete changes in the design and conduct of the REGAIN trial. The REGAIN experience offers a model for future efforts to engage patients as partners in clinical anaesthesia research, and highlights potential opportunities for investigators to increase the relevance of anaesthesia studies by incorporating patient voices and perspectives into the research process.

Objective The types of agents used for monitored anesthesia care (MAC) and their possible differential effects on outcomes have received less study despite increased use over general anesthesia (GA) in transfemoral aortic valve replacements (TAVRs). In this pilot analysis of patients undergoing TAVR using MAC, the authors described the anesthetic agents used and sought to investigate the possible association of anesthetic agent choice with outcomes and the extent to which total weight and time-adjusted doses of anesthetics declined with increasing 10-year age increments. Design Retrospective observational study. Setting Tertiary teaching hospital. Participants Ninety-three participants scheduled to undergo TAVR, with a primary plan of conscious sedation between November 2014 and June 2016, were included. Intervention None. Measurements and Main Results Types of MAC were divided into 4 primary groups, but 2 groups were focused: propofol (n = 39) and dexmedetomidine plus propofol (n = 34). Conversion to GA occurred in 6 participants (6.45%) and was not associated with the type of sedation received. The authors also compared patients who received dexmedetomidine with those who did not in accordance with their a priori analytic plan. There were no associations between the use of dexmedetomidine and postoperative delirium or intensive care unit/hospital length of stay. No significant trends in medication dose adjustments were seen across increasing 10-year age increments. Conclusions A wide breadth of MAC medications is in use among TAVR patients and does not support differences in outcomes. Despite recommendations to reduce anesthetic drug dosing in the elderly, no significant trends in dose reduction with increasing age were noted.

Background Although factor Xa inhibitors have become a popular choice for chronic oral anticoagulation, effective drug reversal remains difficult due to a lack of specific antidote. Currently, 4-factor prothrombin complex concentrate (4F-PCC) is considered the treatment of choice for factor Xa inhibitor-related major bleeding. However, safety of 4F-PCC and its risk of thrombosis when used for this off-label purpose remain unclear. The purpose of this retrospective study is to determine the rate of thromboembolism when 4F-PCC is used for the emergent reversal of factor Xa inhibitors. Methods We conducted a single-center retrospective review of medical records between 2013 and 2017. Patients were included if they received 4F-PCC to reverse rivaroxaban, apixaban, or edoxaban for emergent invasive procedures or during episodes of major bleeding defined as bleeding with hemodynamic instability, fall in hemoglobin of 2 g/dL, or bleeding requiring blood transfusion. Thrombotic events including myocardial infarction, pulmonary embolism, deep vein thrombosis, cerebral vascular accident, and arterial thrombosis of the limb or mesentery were recorded if they occurred within 14 days of 4F-PCC administration. Data was analyzed using point and interval estimation to approximate the rate and confidence interval of thromboembolic events. Results Forty-three patients were identified in our review. Doses of 4F-PCC were determined by the treating physician and mainly ranged from 25 to 50 IU/kg. Twenty-two patients (51.2%) received both sequential compression devices (SCDs) and subcutaneous heparin for DVT prophylaxis. Twenty-one patients (48.8%) were placed on SCDs only. Three patients received concomitant FFP. Thrombotic events within 14 days of 4F-PCC administration occurred in 1 out of 43 patients (2.1%, 95% CI [0.1–12.3]). This thrombotic event was an upper extremity DVT which occurred 1 day after the patient received 1325 IU (25 IU/kg) of 4F-PCC to reverse rivaroxaban for traumatic intracranial hemorrhage. The patient was taken for emergent decompressive craniotomy after rivaroxaban reversal. In patients who did not undergo surgery or who underwent minor invasive procedures, no thrombotic events were noted. Conclusion Based on our preliminary data, the thromboembolic rate of 4F-PCC when given at a dose of 25–50 IU/kg to emergently reverse rivaroxaban and apixaban appears acceptable. Since many patients who require 4F-PCC to emergently reverse factor Xa inhibitors will be at high risk of developing thrombotic events, practitioners should be highly vigilant of these complications. Large, multicenter prospective trials are needed to further determine this risk.

Purpose of review This review discusses the pharmacology of contemporary anesthetic medications in geriatric patients, neurophysiological changes with aging, current recommendations for dosing anesthetic drugs. It also addresses current practice patterns and ongoing studies, which are likely to affect future anesthetic drug management in the elderly. Recent findings Potency of anesthetic drugs is increased in the elderly. In addition to changes at the receptor level, neurophysiological changes in functional connectivity with aging contributes to increased sensitivity of anesthetic drugs. However, the extent of reduction is underappreciated by the practitioners and dose adjustment is not uniformly applied in practice. Large database studies demonstrate association of short-term intraoperative hypotension and CNS depression, to poor perioperative outcomes. These perturbations are probably of greater consequence in frail, elderly patients with reduced reserves. Summary Anesthetic dosing should be more closely age-adjusted to prevent anesthetic-induced hypotension and increased depth of anesthesia in the elderly. Pharmacologic studies are required in the elderly population (>80 years).

Development of hyperglycemia after major operations is very common and is modulated by many factors. These factors include perioperative metabolic state, intraoperative management of the patient, and neuroendocrine stress response to surgery. Acute insulin resistance also develops perioperatively and contributes significantly to hyperglycemia. Hyperglycemia is associated with poor outcomes in critically ill and postsurgical patients. A majority of the investigations use the term "hyperglycemia" very loosely and use varying thresholds for initiating treatment. Initial studies demonstrated improved outcomes in critically ill, postsurgical patients who received intensive glycemic control (IGC) (target serum glucose

Acute kidney injury (AKI) frequently develops after vascular surgery and has a direct impact on short- and long-term outcomes of the patients. Though many aortic pathologies (aneurysms and chronic occlusions) are being managed by stenting and endovascular procedures, the risk of AKI remains appreciable and may be related to contrast-induced kidney injury. This chapter discusses the incidence and risk factors that predispose patients to AKI after vascular surgery. Risk factors are grouped into three broad categories: patient-related factors (these include patient’s age, the presence of chronic kidney disease (pre-procedure or baseline renal function), and proteinuria), surgery-related factors (type and complexity of surgery, emergency surgery, hemodynamic and inflammatory perturbations resulting from the surgery, and specific surgical techniques or maneuvers that may affect renal function), and management-related factors (nephrotoxic drugs, choice of intravenous fluids). Current prophylactic and management strategies that may protect the kidney in patients undergoing vascular procedures are also discussed.

Recent development of noise cancellation devices may offer relief from noise in the intensive care unit environment. This study was conducted to evaluate the effect of noise cancellation devices on subjective hearing assessment by caregivers in the intensive care units.Randomized, double-blind.Adult medical intensive care unit and pediatric intensive care unit of a teaching hospital.Caregivers of patients, including nurses, parents, respiratory therapists, and nursing assistants from a medical intensive care unit and pediatric intensive care, were enrolled in the study.Each participant was asked to wear the headphones, functional or nonfunctional noise cancellation devices, for a minimum of 30 mins.Subjective ambient noise level was assessed on a 10-point visual analog scale (VAS) before and during headphone use by each participant. Headphone comfort and the preference of the caregiver to wear the headphone were also evaluated on a 10-point VAS. Simultaneously, objective measurement of noise was done with a sound level meter using the decibel-A scale and at each of nine octave bands at each bedspace.The functional headphones significantly reduced the subjective assessment of noise by 2 (out of 10) VAS points (p0.05) in environments of equal objective noise profiles, based on decibel-A and octave band assessments.Noise cancellation devices improve subjective assessment of noise in caretakers. The benefit of these devices on hearing loss needs further evaluation in caregivers and critically ill patients.

Certain surgical interventions can perturb the hemostatic system significantly, making the patient prone to intraoperative and postoperative thrombus formation. The consequences of unabated thrombus formation can be devastating. The risk of developing deep vein thrombosis (DVT) after certain surgical procedures can be as high as 40% to 80%, while the incidence of fatal pulmonary embolism is 1% to 5%.11,49 Antithrombotic therapy is usually instituted perioperatively, and has significant impact on the choice of anesthetic technique.1,26 Anticoagulation is an imperative part of vascular reconstructive procedures, as iatrogenic cessation of blood flow and exposure of thrombogenic subepithelial surfaces can act as a nidus for arterial thrombus formation. Furthermore, cardiopulmonary bypass (CPB) procedures with extracorporeal circulation cannot be possible without intraoperative anticoagulation. Intraoperatively, unfractionated heparin (UH) is used most commonly to inhibit coagulation. Although it will likely continue to be used extensively in the near future, newer agents are on the horizon. These agents may be used in clinical situations where heparin is either contraindicated, or where more predictable responses with less side effects are needed. Because of their wide clinical use, it is imperative to be familiar with heparin and the newer anticoagulant agents. Furthermore, surgical interventions, anesthetics, and some commonly used medications affect coagulation. These effects on the hemostatic system will be reviewed, followed by a discussion of antithrombotics, perioperative monitoring, and clinical management. Intraoperative use of thrombolytics and anesthetic implications of anticoagulation will be discussed.

Hyperglycemia in the surgical population is a recognized risk factor for postoperative complications; however, there is little literature to date regarding the management of hyperglycemia in the perioperative period. Here, we detail the strategies that our institutions have employed to identify and treat hyperglycemia in patients with diabetes who present for surgery. Our approach focuses on the recognition of hyperglycemia and metabolic abnormalities, control of glucose levels via insulin infusion when needed, monitoring for hypoglycemia and a comprehensive multidisciplinary approach that provides standardized recommendations for patients at all points in care as they transition from the preoperative clinic into the operating room, and then into the hospital.

The aging process leads to progressive physiological changes. Individuals are more vulnerable to injury at both extremes of age and are more adaptable when bodily injury occurs in adulthood. This chapter will emphasize the changes that one experiences with age. Chronological age refers to age according to birth date, whereas biological age is the estimated age based on the degree of physiological degeneration or loss of physiologic reserve (Lee 2003). Physiologic changes do not necessarily parallel that of chronological age. Furthermore, specific physiological processes may age at different rates in the same individual. In addition to normal physiologic changes that occur with aging, coexisting medical conditions are also more prevalent in the elderly. The normal physiological changes associated with aging are distinct from changes brought on by disease. The pharmacokinetic, pharmacodynamic, neurologic, and cognitive changes in the elderly are affected as much by normal physiology as they are by disease.

Patients with coronary stents undergoing non-cardiac surgery are at increased risk of major adverse cardiovascular events perioperatively. Impeccable patient care and communication between all members of the healthcare team will minimize this risk. The dominant risk factor for stent thrombosis and major adverse cardiovascular events is the interruption of dual antiplatelet therapy (e.g. aspirin and clopidogrel). If clopidogrel therapy has to be interrupted due to increased risk of bleeding, continuation of aspirin is strongly recommended to reduce the risk of stent thrombosis. The interval between percutaneous coronary interventions and operation is the next major risk factor for stent thrombosis. The incidence of major adverse cardiovascular events is inversely related to this interval, with the highest mortality rate occurring

P ATIENTS WHO HAVE significant cardiac disease do poorly perioperatively. Goldman et al’ proposed the landmark Cardiac Risk Index, believing that if patients could be stratified preoperatively according to their risk of suffering cardiac events, appropriate management would reduce perioperative cardiac morbidity and mortality. Goldman’s Cardiac Risk Index Score was used extensively for cardiac risk assessment, but its limitations were soon recognized. Jeffrey et al? demonstrated that the incidence of cardiac complications in patients who had undergone abdominal aortic procedures was higher than that predicted by the Cardiac Risk Index. A high prevalence of occult asymptomatic coronary artery disease was thought to be the reason for significant cardiac morbidity. Hertzer et al3 reported a 90% prevalence of angiographically proven coronary artery disease, 60% of which was severe, in patients who presented for vascular surgery. Exercise stress testing was of limited value in vascular patients because of their limited exercise tolerance. No reliable way of assessing coronary artery disease was available unless a significant number of cardiac catheterization procedures were to be performed in vascular surgery patients. Concurrently, dipyridamole-thallium imaging (DTI) was introduced in clinical practice as a means of assessing myocardial blood supply. This test had a number of advantages compared with cardiac catheterization. It was noninvasive; was not dependent on the level of exercise achieved by patients; and it defined the location and extent of myocardium at risk (redistribution), permanently damaged (fixed defect), or normal. Absence of redistribution on DTI was reported to signify virtually no risk of sustaining a perioperative myocardial event (negative predictive value, 95% to lOO%).4 With such a high negative predictive value, DTI was rapidly accepted as the most appropriate test for cardiac risk assessment in vascular surgery patients. Should DTI be recommended as a routine preoperative test in patients scheduled for vascular surgery? The author believes that DTI should not be recommended as a routine preoperative test. This conclusion is based on several factors, which are discussed as follows: (I) the true value of the test in cardiac risk stratification, (2) the effect of a positive DTI test on the perioperative management of the patient and overall outcome, (3) the impact of current incidence of the disease and patient outcome on the utility of DTI, and (4) the cost involved. The major shortcomings of most of the initial studies that showed the high negative predictive value of DTI was that they were retrospective and associated with a selection bias. The results were available to the physicians and influenced their anesthetic and surgical management.5 Prospective studies have not supported these retrospective observations.6-Q Mangano et al6 studied 60 consecutive vascular surgery patients who underwent DTI preoperatively. Caregivers were blinded to DTI results, and no significant difference in perioperative ischemia was noted among patients with normal DTI, with fixed defects, or with thallium redistribution.‘j Baron et al,7 in their study of 457 patients who underwent abdominal aortic aneurysm repairs, showed that the presence of clinical evidence of coronary artery disease and old age were the most important preoperative predictors of an adverse cardiac event, rather than thallium redistribution. Similarly, Seeger et al* could not find a significant difference in cardiac complications between patients with positive DTI (redistribution) and negative DTI (fixed or no defect). Roghi et al9 corroborated these findings in 220 vascular surgery patients and reported that redistribution defects had limited sensitivity (38%) and specificity (63%) to predict adverse cardiac outcomes. Positive predictive value and negative predictive value of redistribution were 14% and 87% in their study.g With the benefits of DTI in question, Eagle et ali0 evaluated the advantage of combining clinical indices with DTI results. DTI per se did not enhance the ability to predict perioperative cardiac morbidity in patients who were already assessed by clinical criteria to be at low risk of sustaining cardiac problems (ie, no Eagle’s criteria: Q waves, diabetes mellitus, age > 70 years, angina, ventricular arrhythmias). Similarly, in patients who had three or more of the criteria defined by Eagle, the chance of having significant coronary artery disease and sustaining perioperative events was high. The presence of thallium redistribution raised the risk only from 50% to 64%; and even in the absence of thallium redistribution, the event rate was 33%.t” Eagle et alto suggested that DTI is indicated in determining the myocardium at risk in patients who are at an intermediate risk by clinical criteria (one or two of Eagle’s criteria). Based on the results of DTI, this selective patient population can then be classified as low or high risk. This suggestion has been validated further in a cohort of 1,081 vascular surgical patients by L’italien et al and meta-analysis of DT imaging (19841994) for risk stratification.r*~** These investigations support that DTI has only a limited role in a selective subset of vascular surgery patients, and routine preoperative screening is not advocated. Another factor that the proponents of DTI have promoted arduously is its value in predicting long-term morbidity and mortality. This is an important observation, but it should not be extrapolated to mean petioperative benefit. It is becoming more evident that it may be more prudent to consider DTI in the overall management of coronary artery disease patients, independent of the plans for surgery. The value of DTI in risk stratification in vascular surgery patients has been discussed (see earlier). It is of more limited value when considering the impact of a positive test on perioperative management. The chance of sustaining a pexioperative myocardial infarction is fourfold greater in a patient with a

Inflammation is associated with the pathogenesis of coronary atherosclerosis, although the mechanisms remain unclear. We investigated whether cytokine secretion by innate immune responses could contribute to the production of proarteriosclerotic Th1-type cytokines in human coronary atherosclerosis. Cytokines were measured by ELISA in the plasma of patients with coronary atherosclerosis undergoing cardiac catheterization. IL-18 was detected in all subjects, whereas a subset of patients demonstrated a coordinated induction of other IFN-γ-related cytokines. Specifically, elevated plasma levels of IL-12 correlated with that of IFN-γ and IFN-γ-inducible chemokines, defining an IFN-γ axis that was activated independently of IL-6 or C-reactive protein. Systemic inflammation triggered by cardiopulmonary bypass increased plasma levels of the IFN-γ axis, but not that of IL-18. Activation of the IFN-γ axis was not associated with acute coronary syndromes, but portended increased morbidity and mortality after 1-year follow-up. IL-12 and IL-18, but not other monokines, elicited secretion of IFN-γ and IFN-γ-inducible chemokines in human atherosclerotic coronary arteries maintained in organ culture. T cells were the principal source of IFN-γ in response to IL-12/IL-18 within the arterial wall. This inflammatory response did not require, but was synergistic with and primed for TCR signals. IL-12/IL-18-stimulated T cells displayed a cytokine-producing, nonproliferating, and noncytolytic phenotype, consistent with previous descriptions of lymphocytes in stable plaques. In contrast to cognate stimuli, IL-12/IL-18-dependent IFN-γ secretion was prevented by a p38 MAPK inhibitor and not by cyclosporine. In conclusion, circulating IL-12 may provide a mechanistic link between inflammation and Th1-type cytokine production in coronary atherosclerosis.

Objective: Several studies suggest that cardiac troponin-I (cTn-I) is a more sensitive indicator of cardiac injury compared with other biochemical markers of injury, but the strategy with the highest diagnostic yield (true positive and true negative) for perioperative surveillance is unknown. The authors undertook a prospective evaluation of the perioperative incidence of myocardial infarction (MI) and evaluated surveillance strategies for the diagnosis of MI. Design: Prospective, cohort study. Setting: Two university hospitals. Participants: Four hundred sixty-seven high-risk patients requiring noncardiac surgery. Interventions: None. Measurements and Main Results: The diagnosis of myocardial injury was determined by cardiac protein markers combined with either postoperative changes on 12-lead electrocardiography or 1 of 3 clinical symptoms consistent with MI (chest pain, dyspnea, requirement for hemodynamic support). A receiver operating characteristic curve evaluating troponin in the diagnosis of MI revealed a value of 2.6 ng/mL as having the highest sensitivity and specificity. The sensitivity and specificity of cTn-I value ≥2.6 ng/mL, troponin ≥1.5 ng/mL, total creatine kinase (CK) ≥170 IU/L with MB ≥5%, and CK-MB ≥8 ng/mL were compared. Surveillance strategies were determined on a subset of patients (n = 257). The incidence of MI was 9.0% by cTn-I ≥2.6 ng/mL criteria, 19% by cTn-I ≥1.5 ng/mL, 13% by CK-MB mass, and 2.8% by CK-MB%. The specificity of cTn-I ≥2.6 ng/mL as an indicator of MI was 98%, and its positive predictive value (PPV) was 85%. Cardiac troponin-I ≥2.6 ng/mL had equal specificity but greater PPV than the cTn-I ≥1.5 ng/mL (specificity 98% and PPV 79%). If surveillance of cTn-I ≥2.6 ng/mL was used to detect MI, then the strategy with the highest diagnostic yield was surveillance on postoperative days 1, 2, and 3. Conclusions: Perioperative cardiac injury continues to occur frequently after noncardiac surgery, as detected by cTn-I. Serial monitoring of cardiac troponin-I on postoperative days 1, 2, and 3 provides the strategy with the highest diagnostic yield for surveillance of MI.

Objective Review the perioperative management of patients who are scheduled for noncardiac surgery. Data source Review of literature (PubMed, MEDLINE). Conclusions Patients with ischemic heart disease who undergo noncardiac surgery are at significant risk of perioperative cardiac morbidity and mortality. Recent joint guidelines from the American College of Cardiology and American Heart Association have significantly streamlined the preoperative evaluation processes. Augmented hemodynamic control with intensive perioperative pharmacologic therapy with beta-blockers and possibly alpha-2 agonist has been shown to improve perioperative cardiovascular outcomes. However, translating this information to clinical practice continues to be a challenge and requires a multi- disciplinary approach. A particular intraoperative anesthetic technique is unlikely to influence perioperative cardiac morbidity and mortality. Postoperative management with goals of decreasing hemodynamic stress is important in patients with ischemic heart disease. Diagnosis and management of perioperative myocardial infarction continues to be a challenge. However, use of cardiac specific biomarkers should improve the diagnostic process.

PURPOSE OF REVIEW The publication of Van den Berghe's landmark study in 2001 supported the use of intensive insulin therapy (IIT) to target normoglycemia in the critically ill and triggered a new era in glycemic management in the perioperative period and in the ICU. In 2009, the normoglycemia in intensive care evaluation-survival using glucose algorithm regulation (NICE-SUGAR) trial demonstrated increased mortality and incidence of hypoglycemia in patients managed with IIT, resulting in a shift toward higher blood glucose targets in this patient population. This review distills clinically pertinent principles from the related literature published in the months since the NICE-SUGAR trial. RECENT FINDINGS A target blood glucose level in the acute care setting supported by many of the pertinent societies and frequently quoted in the literature is 140-180 mg/dl. Hyperglycemia, hypoglycemia, and glucose variability are detrimental. Accurate and efficient glucose monitoring devices are essential. Insulin infusion protocols (IIPs) employed to achieve desired blood glucose targets must be individualized and validated for the ICU and institution in which they are being implemented. SUMMARY Appropriate glycemic management in the acute care setting can be achieved by targeting a reasonable blood glucose range and employing specific and institutionally validated IIPs.

Patients undergoing vascular surgery have a high risk of suffering major postoperative cardiac events.Preoperative myocardial ischemia as detected by Holter monitoring identifies a high-risk subgroup whose postoperative ischemia, similarly detected, seems to herald major cardiac events. In this stud