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The purpose of this review is to discuss the pharmacological management of the common symptoms that palliative trauma patients experience at the end of life. The value of palliative care in trauma patients is increasingly being recognized through its positive impact on patients' symptom management, quality of life, and health care costs. There is a strong correlation between early recognition and intervention of symptoms and improvement in patients’ end-of-life care. Adequate palliative care includes effective pharmacological symptom management and a multidisciplinary team approach, especially in trauma patients. Palliative care and symptom management in trauma patients can be complex and present with unique challenges. Palliative care in trauma patients is evolving, and adequately trained staff should be involved in the care of these vulnerable patients. Effective pharmacotherapy can optimize patient care, symptoms, and quality of life.

Background/objectives Advanced age is associated with increased susceptibility to acute adverse effects of propofol. The present study aimed to describe patterns of propofol dosing for induction of general anesthesia before endotracheal intubation in a nationwide sample of older adults presenting for surgery. Design Retrospective observational study using the Multicenter Perioperative Outcomes Group data set. Setting Thirty-six institutions across the United States. Participants A total of 350,766 patients aged over 65 years who received propofol for general anesthetic induction and endotracheal intubation between 2014 and 2018. Intervention None. Measurements Total induction bolus dose of propofol administered. Results The mean (SD) weight-adjusted propofol dose was 1.7 (0.6) mg/kg. The mean prevalent propofol induction dose exceeded the upper bound of what has been described as the typical geriatric dose requirement across every age category examined. The percent of patients receiving propofol induction doses above the described typical geriatric range was 64.8% (95% CI 64.6-65.0), varying from 73.8% among patients aged 65-69 to 45.8% among patients aged 80 and older. Conclusion The present study of a large multicenter cohort demonstrates that prevalent propofol dosing commonly falls above the published typically required dose range for patients aged ≥65 in nationwide anesthetic practice. Widespread variability in induction dose administration remains incompletely explained by known patient variables. The nature and clinical consequences of these unexplained dosing decisions remain important topics for further study. Observed discordance between expected and actual induction dosing raises the question of whether there should be reconsideration of widespread provider practice or, alternatively, whether what is published as the typical propofol induction dose range should be revisited.

BACKGROUND/OBJECTIVES: In the context of an aging surgical population, appropriate anesthetic induction dose adjustments for the older adult remain poorly defined. In the present study, we describe the prevalence of excess induction agent dose in reference to Food and Drug Administration (FDA) guidance and seek to investigate the possible association of such excess dose with postinduction hypotension and postoperative acute kidney injury. Study Design A retrospective observational study was conducted in a large tertiary teaching hospital in accordance with our a priori analytic protocol as registered on ClinicalTrials.gov (NCT03699696). For inclusion, patients must have been 65 years or older and received general anesthesia with propofol induction for gynecologic oncology surgery between December 1, 2014 and July 8, 2018. Descriptive variables of the patients, machine-captured perioperative vital signs, induction anesthetic, and vasopressor/inotrope administrations were recorded. MAIN OUTCOME MEASURES: A total of 541 female patients met inclusion criteria. The mean (SD) age of the cohort was 72.20 (5.93). Regarding the primary outcome, 65.43% (354 patients, 95% CI of 61.2%−69.4%) of the cohort received more than the FDA recommended 1–1.5mg/kg induction dose for patients of advanced age undergoing general anesthesia. RESULTS: The percent of patients receiving doses in excess of FDA guidance remained substantial across all age groups but decreased progressively with increasing 5-year age intervals (from 74% among those aged 65–69 to 44% among those aged >80). Excess propofol dose in the present cohort was not associated with our a priori definition of postinduction hypotension. Regarding AKI, among the 30 patients suffering this outcome, it occurred less often in patients who received higher propofol doses (4.2% (9/217) vs. 15.3% (21/138), p

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.

Objectives To characterize the association between the use of physiologic assessment (central venous pressure, pulmonary artery occlusion pressure, stroke volume variation, pulse pressure variation, passive leg raise test, and critical care ultrasound) with fluid and vasopressor administration 24 hours after shock onset and with in-hospital mortality. Design Multicenter prospective cohort study between September 2017 and February 2018. Settings Thirty-four hospitals in the United States and Jordan. Patients Consecutive adult patients requiring admission to the ICU with systolic blood pressure less than or equal to 90 mm Hg, mean arterial blood pressure less than or equal to 65 mm Hg, or need for vasopressor. Interventions None. Measurement and main results Of 1,639 patients enrolled, 39% had physiologic assessments. Use of physiologic assessment was not associated with cumulative fluid administered within 24 hours of shock onset, after accounting for baseline characteristics, etiology and location of shock, ICU types, Acute Physiology and Chronic Health Evaluation III, and hospital (beta coefficient, 0.04; 95% CI, -0.07 to 0.15). In multivariate analysis, the use of physiologic assessment was associated with a higher likelihood of vasopressor use (adjusted odds ratio, 1.98; 95% CI, 1.45-2.71) and higher 24-hour cumulative vasopressor dosing as norepinephrine equivalent (beta coefficient, 0.37; 95% CI, 0.19-0.55). The use of vasopressor was associated with increased odds of in-hospital mortality (adjusted odds ratio, 1.88; 95% CI, 1.27-2.78). In-hospital mortality was not associated with the use of physiologic assessment (adjusted odds ratio, 0.86; 95% CI, 0.63-1.18). Conclusions The use of physiologic assessment in the 24 hours after shock onset is associated with increased use of vasopressor but not with fluid administration.

The choice of anesthetic for carotid endarterectomy (CEA) continues to be controversial. Recent literature suggests improved outcomes with the use of regional anesthesia (RA) compared with general anesthesia (GA). The objective of this study was to examine the utilization and outcomes of RA for CEA using a national database.The targeted CEA files of the American College of Surgeons' National Surgical Quality Improvement Program (2011-2017) were reviewed. Patients were stratified based on anesthesia type into RA and GA, and patients' characteristics were compared between the 2 groups. The outcomes of CEA under GA and RA were compared after 2:1 propensity matching.There were 26,206 CEAs, and 14% (n = 3,664) were performed under RA, with no change in relative utilization during the study period (P = 0.557). Patients treated under RA were more likely to be older than 65 years (80.6% vs. 75.8%; P 0.001) and White (90.8% vs. 83.5%; P 0.001) but less likely to have diabetes (28.2% vs. 31.2%; P = 0.001), chronic obstructive pulmonary disease (10.2% vs. 10.5%; P 0.001), and heart failure (1.0% vs. 1.5%; P = 0.02) and be symptomatic (37.4% vs. 42.7%; P 0.001). After matching, there was no significant difference in baseline characteristics between the 2 groups. Patients undergoing RA were less likely to experience the combined end point of stroke, myocardial infarction, or mortality compared with GA. GA patients were more likely to have longer operating time and hospital length of stay.CEA performed under RA is associated with improved outcomes compared with GA. RA is underutilized in carotid surgery, and strategies to optimize its use are needed.

In the current COVID-19 crisis, the US and many countries in the world are suffering acute shortages of modern ventilators to care for desperately ill patients. Since modern ICU ventilators are powerful devices that can deliver very high gas flow rates and pressures, multiple physicians have attempted to ventilate more than one patient on a single ventilator – so-called “vent splitting”. Early applications of this approach have utilized simple concatenations of ventilator tubing and T-pieces, to provide flow to more than one patient. Additional approaches using custom flow splitters – sometimes made using 3D printing technologies – have also advanced into the clinic with FDA approval. However, heretofore there has been less progress made on controlling individual ventilatory pressures for patients with severe lung disease. Given the inherent variability and instability of lung compliance amongst patients with COVID-19, there remains an important need to provide a means of extending ventilator usefulness to more than one patient, but in a way that provides more tailored pressures that can be titrated over time. In this descriptive report, we provide the basis for a ventilator circuit that can support two patients with individualized peak inspiratory and end-expiratory pressures. The circuit is comprised of exclusively “off the shelf” materials and is inexpensive to produce. The circuit can be used with typical ICU ventilators, and with anesthesia ventilators used in operating rooms. Inspiratory and end-expiratory pressures for each patient can be titrated over time, without changes for one patient affecting the ventilation parameters of the other patient. Using in-line spirometry, individual tidal volumes can be measured for each patient. This Pressure-Regulated Ventilator Splitting (PReVentS) Yale University protocol operates under a pressure-control ventilatory mode, and may function optimally when patients are not triggering breaths from the ventilator.This method has been tested thus far only in the laboratory with mock lungs, and has not yet been deployed in animals or in patients. However, given the novelty and potential utility of this approach, we deemed it appropriate to provide this information to the broader critical care community at the present time. In coming days and weeks, we will continue to characterize and refine this approach, using large animal models and proof-of-principle human studies.

Increasing number of very old patients (> 80 year old) are presenting for invasive procedures and surgeries. This review addresses perioperative outcomes after cardiac and non-cardiac surgery, in octogenarians and older patients. The overall rates of major upper abdominal cancer resections in octogenarians are increasing over time. Postoperative mortality, postoperative admission to the intensive care unit, and discharge to non-home disposition, after emergency general surgery, were strongly associated with age greater than 80 years. Though acceptable, perioperative morbidity and mortality tends to increase non-linearly after the age of 75 years in patients undergoing cardiac operations. Clinician-centric outcomes continue to dominate outcome reporting. Octogenarians have higher risk of mortality and increased rates of complications, both after cardiac and non-cardiac surgeries. Perioperative care is more resource intensive in the elderly. It is important to keep these factors in mind when contemplating interventions in very elderly individuals.

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.

Despite guidelines suggesting a 25–50 % reduction in induction doses of intravenous anesthetic agents in the elderly (≥65 years), we hypothesized that practitioners were not sufficiently correcting drug administration for age, contributing to an increased incidence of hypotension in older patients undergoing general anesthesia. We conducted a retrospective, observational study in a tertiary-care academic hospital. The study included 768 female patients undergoing gynecologic surgeries who received propofol-based induction of general anesthesia. Weight-adjusted anesthetic induction dosing, age-associated differences in dosing by ASA-PS (American Society of Anesthesiology—Physical Status), and hemodynamic outcomes between younger (18–64 years, n = 537) and older (≥65 years, n = 231) female patients were analyzed. Older patients received lower doses of propofol and midazolam than younger patients (propofol: 2.037 ± 0.783 vs 2.322 ± 0.834 mg/kg, p

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).

Red blood cell (RBC) transfusion has been linked to increased morbidity and mortality. However, strict RBC transfusion recommendations recently have been questioned. The aim of this study was to investigate the short- and long-term mortality outcomes after RBC transfusion in patients undergoing coronary artery bypass graft surgery (CABG).This was a retrospective medical record review.Tertiary care academic medical center.The study included patients who underwent CABG from June 2006 to May 2013.Adult (18 years) cardiac surgery patients who were admitted to the cardiothoracic intensive care unit in a tertiary care academic medical center from June 2006 to May 2013 were collected. In all, 2,180 patients who underwent CABG surgery were included into propensity-score matching analyses, which were matched 1:1. Patients who did not receive transfusion of packed red blood cells (PRBC) (n = 937) were compared with those who received 1 to 5 U (n = 1,113). The study outcomes included mortality rates at 1, 3, and 6 months (short-term) and 1, 2, 3, and 4 years (long-term).No statistical significant differences were found for the 1-month (2% v 1.1%, p = 0.292), 3-month (2.9% v 2%, p = 0.396), or 6-month mortality rate (4.3% v 3.4%, p = 0.602) in 446 patients with 1 to 5 U versus 446 matched patients with no PRBC transfusion. Patients in the transfused group compared with those in the no-transfusion group had statistically significant higher 3-year mortality rate (11% v 6.7%; hazard ratio, 1.64; 95% confidence interval, 1.03-2.63; p = 0.038).In the present study, patients undergoing CABG surgery and receiving6 U of PRBC did not have statistically increased risk for in-hospital mortality and up to 2 years postoperatively. A modestly statistically significant difference was noted at 3 years. However, cumulatively, there was no statistical difference between the transfused and nontransfused groups at 4 years. Further studies are needed to confirm the findings and define the population that will benefit the most from blood transfusion.

It is recommended to correct intravenous induction doses by up to 50% for patients older than 65 years. The objectives were to determine (a) the degree to which anesthesia providers correct induction doses for age and (b) additionally adjust for American Society of Anesthesiologists physical status (ASA-PS) class (severity of illness) and (c) whether postinduction hypotension is more common among patients aged65.Retrospective chart review.Academic medical center.A total of 1869 adult patients receiving general anesthesia for GI surgical procedures from February 2013 to January 2014.Patients were divided into 3 age groups (age65, 65-79, ≥80 years) and then further stratified into ASA-PS class (I/II vs III/IV). Multiple pairwise comparisons were conducted using Welch t tests for continuous variables to determine whether dosing was different for the older groups vs the younger group; separate analyses were performed within and across ASA-PS class. This approach was also used to determine differences in mean arterial pressure change in the older groups vs the younger group, whereas the rates of hypotension among different age groups were compared by Cochran-Armitage trend test.No significant decrease in dosing between age groups was observed for fentanyl and midazolam. For propofol, there was a significantly lower dosing for older patients: 17% for patients aged 65-79 and 29% for those aged80, which was still in less than the recommendations. An inverse relationship was observed between propofol dosing and ASA-PS class, but no consistent relationship was noted for fentanyl and midazolam. There were a significantly larger drop in mean arterial pressure and a greater likelihood of hypotension following induction in patients aged 65-79 years and80 years as compared with those aged65 years.This study shows that the administered dose of anesthetic induction agents is significantly higher than that recommended for patients older than 65 years. This failure to age-adjust dose may contribute to hypotensive episodes.

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

To determine if recommendations regarding perioperative beta-blocker therapy were followed by an increase in the number of eligible presurgical patients receiving beta-blockers and the number achieving the recommended heart rate (HR60 beats per minute [bpm]).Retrospective, observational study.Tertiary-care teaching hospital.The records of all 718 patients who underwent elective vascular surgery or coronary artery bypass grafting between January 2001 and March 2002 (pre-guideline) and those who did so between April 2002 and September 2003 (post-guideline) were reviewed. Percentage of eligible patients who received beta-blockers preoperatively and the target HR achieved in pre-guideline versus post-guideline patients were recorded. Differences were assessed using the unpaired t test and chi2 analysis. A P value of less than 0.05 is reported.Fifty percent of the post-guideline patients in the vascular surgery group were receiving beta-blockers at the time of preanesthetic evaluation versus 48% of pre-guideline patients (P = nonsignificant [NS]). Mean HR in the vascular surgery post-guideline beta-blocker group (70 +/- 14 bpm) was higher than in the pre-guideline beta-blocker group (65 +/- 11 bpm) (P0.01). Only 22% of those vascular surgery patients in the post-guideline group who were taking beta-blockers achieved the target HR of less than 60 bpm versus 29% of the vascular surgery patients taking beta-blockers in the pre-guideline group (P = NS). In the coronary artery bypass grafting group, 80% of post-guideline patients received beta-blocker before anesthesia assessment versus 75% of pre-guideline patients (P = NS). Mean HR in the post-guideline beta-blocker group (67 +/- 15 bpm) was similar to the pre-guideline beta-blocker group (64 +/- 13 bpm) (P = NS). Only 28% of the post-guideline patients who were receiving beta-blockers achieved the target HR of less than 60 bpm, which was not significantly different from the 17% achieved in the pre-guideline group (P = NS).At our institution, preoperative beta-blocker use was not significantly changed by publication of the recommendations.

Background—Heparin, used clinically as an anticoagulant, also has antiinflammatory properties and has been described to inhibit interferon (IFN)-γ responses in endothelial cells. We investigated the effects of heparin on the IFN-γ–inducible chemokines IP-10/CXCL10, I-TAC/CXCL11, and Mig/CXCL9, which play important roles in the vascular recruitment of IFN-γ–producing Th1 cells through interactions with their cognate receptor, CXCR3.Methods and Results—Patients undergoing coronary artery bypass grafting were studied because coronary atherosclerosis is recognized as a Th1-type inflammatory disease and the subjects required systemic heparinization. Plasma levels of IP-10, I-TAC, and Mig increased immediately after heparin administration and diminished promptly after heparin antagonism with protamine. These effects were independent of detectable circulating IFN-γ or the IFN-γ inducer interleukin-12. We confirmed previous reports that heparin inhibits the IFN-γ–dependent production of CXCR3 chemokine ligands using atherosclerotic coronary arteries in organ culture. In addition to prolonged treatment decreasing chemokine secretion, heparin rapidly displaced membrane-associated IP-10 from cultured endothelial cells that did not express CXCR3 and reduced the IP-10–dependent transendothelial migration of T helper cells under conditions of venular shear stress. Finally, heparin administration to immunodeficient mouse hosts decreased both the recruitment and accumulation of memory T cells within allogeneic human coronary arteries.Conclusions—Besides inhibiting IFN-γ responses, heparin has further immunomodulatory effects by competing for binding with IP-10, I-TAC, and Mig on endothelial cells. Disruption of CXCR3+Th1 cell trafficking to arteriosclerotic arteries may contribute to the therapeutic efficacy of heparin in inflammatory arterial diseases, and nonanticoagulant heparin derivatives may represent a novel antiinflammatory strategy.

To quantify the prevalence of perioperative beta-blocker use and its impact on preoperative and preinduction heart rate (HR), in light of the recent publication of specific recommendations regarding perioperative beta-blocker use and desired HR.Retrospective observational study in patients who underwent elective and coronary artery bypass graft (CABG) surgery between January 2001 and March 2002.Tertiary-care teaching hospital.Percentage of eligible patients who received beta-blockers preoperatively and the impact of non-protocol-based beta-blocker therapy on preadmission and preinduction HR were recorded. Differences were assessed with unpaired t test and chi(2) analysis; P.05 was considered significant, with corrections for multiple comparisons.Of the patients who underwent vascular surgery, 9 had documented prior beta-blocker intolerance. Of the remaining 172 patients, 94.8% had indication for perioperative beta-blocker use. However, only 47.7% of the eligible patients received beta-blockers. Of the 155 CABG patients, 74.2% were taking beta-blockers preoperatively. Only 29% of vascular patients and 32% of CABG patients who were receiving beta-blockers had HR less than 60 beats per minute (bpm) at preadmission. The mean preadmission HR in vascular surgery patients was 65.2 +/- 11 and 73.2 +/- 13.8 bpm in beta-blocker and non-beta-blocker patients, respectively (P = .0001). In CABG surgery patients, preadmission HR values were 64.2 +/- 13 and 76.1 +/- 12 bpm in beta-blocker and non-beta-blocker patients, respectively (P = .001). The preinduction HR subsequently increased in the beta-blocker as well as in the non-beta-blocker groups.Only half of the patients who qualify to receive preoperative beta-blockers by current recommendations actually receive them before noncardiac surgery, and the majority of these patients have preadmission and preinduction HR less than 60 bpm. Targeting beta-blocker therapy treatment to an HR less than 60 bpm may not be readily achievable in many patients.

Beta-blockers have emerged as one of the key therapeutic agents that can decrease cardiac morbidity and mortality. Advances in cardiac beta-adrenergic receptor physiology and pharmacology have provided new insights into the beneficial effects of beta-blockers in cardiovascular medicine. Although significant advances have been made, many specific questions still remain to be answered. We will review some of these developments and the current role of beta-blockers in peri-operative medicine.

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.

Use of ultrasound in the acute care setting has become more common in recent years. However, it still remains underutilized in the perioperative management of critical patients. In this review, we aim to increase the awareness of ultrasound as an important diagnostic modality that can be used in the perioperative period to improve patient care. Our main focus will be in describing the diagnostic uses of ultrasound to identify cardiac, pulmonary, airway and vascular diseases commonly encountered in acute care settings.We find that ultrasound can be used in a quick fashion to assess a haemodynamically unstable patient. Protocols are available to use ultrasound as a part of cardiopulmonary resuscitation. Ultrasound can help in deciding fluid vs. pressor treatment by evaluating the inferior vena cava and other cardiac structures.Lung ultrasound can not only help in diagnosing pneumothoracies and effusions but also look at lung recruitment and diaphragmatic movement, hence can aid in deciding extubation strategies. This modality can be utilized for confirmation of endotracheal tube.Recent interest in axillary vein cannulation with ultrasound guidance has gained some momentum.This article covers the recent developments and literature available on point of care ultrasound and its utilization in the perioperative period. We have not covered some other important uses of ultrasound such as abdominal examination looking at the aorta and other abdominal organs. This was beyond the scope of this article.

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.

Objectives Intraparenchymal airways are involved in air flow regulation. Relaxation of intraparenchymal airways to volatile anesthetics varied by topographic location. This study was conducted to determine whether other bronchodilators (terbutaline, diltiazem, and aminophylline) relax bronchiolus to a greater degree than bronchus, as seen with volatile anesthetics. Design In vitro, controlled, randomized study. Setting Animal research laboratory. Subjects Adult dogs (n = 9). Interventions Proximal (outer diameter, 4-6 mm) and distal (outer diameter, 0.8-1.5 mm) airway rings of dogs were contracted in tissue baths with the effective concentration of acetylcholine that produces half the maximum response. Airway relaxant dose-response curves were constructed to measure isometric tension after administration of terbutaline (concentration range, 10(-8) to 10(-4) M), diltiazem (concentration range, 3 x 10(-7) to 1 x 10(-4) M), and aminophylline (concentration range, 10(-7) to 10(-4) M). Measurements and main results All three bronchodilators caused relaxation of the proximal and distal airways. At the maximum dose, diltiazem (maximum relaxation, 95%+/-2% [proximal], 94%+/-6% [distal]; p > .05) was the most efficacious, followed by terbutaline (maximum relaxation, 72%+/-13% [proximal], 55%+/-9% [distal]; p .05. At the concentrations tested, they were equally efficacious. No significant differences in relaxation between proximal and distal airways were noted with diltiazem or aminophylline in the entire dose range. However, terbutaline relaxed the distal airway more than the proximal airway in the entire dose range. Conclusions The results demonstrate that only terbutaline showed a differential airway relaxant effect between proximal and distal airways, as seen with volatile anesthetics.

Over a 100 million adults undergo noncardiac surgery worldwide, and a significant proportion of these patients are elderly patients with complex medical histories undergoing vascular surgery. The risk of adverse events, especially cardiac events, increases with age. Elderly patients with significant comorbidities who undergo high-risk procedures are more likely to sustain perioperative adverse events than their healthy counterparts in the same age cohort. Perioperative management of elderly patients scheduled for vascular surgery poses a unique challenge for the anesthesiologist. This chapter will focus on the demographics of an elderly patient presenting for vascular surgery, risks of commonly performed vascular procedures, preoperative evaluation, and perioperative management of elderly patients undergoing vascular surgery.

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.