Relationship Between Glucose Time in Range in Diabetic and Non-Diabetic Patients and Mortality in Critically Ill Patients.

Background: Shorter time spent in specific blood glucose ranges is associated with mortality benefit in critically ill patients. However, various time in range values are reported, each based on a specific blood glucose range. Objective: To evaluate relationship between percentage of time spent at various blood glucose ranges (TIR) and mortality in critically ill patients. Methods: Single-center, retrospective, cohort study that included adult patients admitted to ICU for at least one day. We evaluated the relationship between TIR at prespecified blood glucose ranges and hospital mortality in diabetic and non-diabetic patients Results: Of the 5287 patients included, 3705 (70.0%) were non-diabetic and 1582 were diabetic (29.9%). Diabetic patients had higher in-hospital mortality rate (15.8%) compared to non-diabetic patients (11.3%), p < 0.0001, and with higher incidence of hyperglycemia (77.8% vs. 39.4%) and hypoglycemia (14.3% vs. 10%) compared to non-diabetic patients, p < 0.0001. The highest median TIR for both diabetic [76% (49.1 - 97.8%)] and non-diabetic patients [100% (92.3--100%)] was at blood glucose range of 70-180 mg/dL. In non-diabetic cohort, the only optimal TIR of 40% at blood glucose range of 70-120 mg/dL was identified. Non-diabetic patients stratified into TIR 70-120 mg/dL > 40% reported significantly lower mortality (7.0%) rate compared to patients with TIR 70-120 mg/dL < 40% (15.7%), OR 0.52, 95% CI 0.27-0.97, adjusted-p = 0.03. In diabetic patients, no relationship was detected between TIR at all predefined glucose ranges and hospital mortality. Conclusion: Critically ill non-diabetic patients who spent at least 40% of time in blood glucose range of 70-120 mg/dL had improved survival. This association was not observed in diabetic patients.

Pressure-Regulated Ventilator Splitting for Disaster Relief: Design, Testing, and Clinical Experience.

The coronavirus disease 2019 (COVID-19) pandemic has revealed that even the best-resourced hospitals may lack sufficient ventilators to support patients under surge conditions. During a pandemic or mass trauma, an affordable, low-maintenance, off-the-shelf device that would allow health care teams to rapidly expand their ventilator capacity could prove lifesaving, but only if it can be safely integrated into a complex and rapidly changing clinical environment. Here, we define an approach to safe ventilator sharing that prioritizes predictable and independent care of patients sharing a ventilator. Subsequently, we detail the design and testing of a ventilator-splitting circuit that follows this approach and describe our clinical experience with this circuit during the COVID-19 pandemic. This circuit was able to provide individualized and titratable ventilatory support with individualized positive end-expiratory pressure (PEEP) to 2 critically ill patients at the same time, while insulating each patient from changes in the other's condition. We share insights from our experience using this technology in the intensive care unit and outline recommendations for future clinical applications.

Preoperative evaluation of geriatric patients undergoing liver transplantation.

PURPOSE OF REVIEW: As the population of the world is aging the number of geriatric patients undergoing liver transplantation (LT) is also increasing. They pose a unique challenge for the caregivers, as they have age-related physiological changes, multiple comorbidities and cirrhosis-related pathologies. RECENT FINDINGS: Twenty-two percent of patients who undergo LT are older than 65 years. Many patients suffer from nonalcoholic steatohepatitis (NASH), hepatocellular carcinoma and hepatitis-C virus. Incidence of NASH tends to increase with age, obesity, diabetes and metabolic syndrome. Elderly patients require comprehensive cognitive, cardiac and pulmonary evaluation prior to LT. Cirrhotic cardiomyopathy, hepatopulmonary syndrome, portopulmonary hypertension and frailty are of specific concern. SUMMARY: Proportion of elderly patients who are undergoing LT continues to increase. These patients require comprehensive cardiopulmonary and frailty evaluation. Consensus-based practice advisories need to be developed to standardize preoperative evaluation of geriatric patients awaiting LT.

Regional Anesthesia is Underutilized for Carotid Endarterectomy Despite Improved Perioperative Outcomes Compared with General Anesthesia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Association of red blood cell transfusion and short- and longer-term mortality after coronary artery bypass graft surgery.

OBJECTIVE: 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). DESIGN: This was a retrospective medical record review. SETTING: Tertiary care academic medical center. PARTICIPANTS: The study included patients who underwent CABG from June 2006 to May 2013. INTERVENTION: 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). RESULTS: 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). CONCLUSION: In the present study, patients undergoing CABG surgery and receiving <6 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.

A Pilot Analysis of the Association Between Types of Monitored Anesthesia Care Drugs and Outcomes in Transfemoral Aortic Valve Replacement Performed Without General Anesthesia.

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.

Pharmacological considerations in the elderly.

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).

Utility of ultrasound in the ICU.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.

Association of propofol induction dose and severe pre-incision hypotension among surgical patients over age 65.

STUDY OBJECTIVE: We aimed to study the association between propofol induction dose (mg/kg) and pre-incision severe hypotension (Mean Arterial Pressure (MAP) ≤ 55 mmHg) among patients ≥65 years of age. DESIGN: Retrospective Observational. SETTING: 40 centers participating in the Multicenter Perioperative Outcomes Group consortium. PATIENTS: Patients ≥65 years of age undergoing non-cardiac, non-vascular surgery who received propofol for general anesthetic induction prior to endotracheal intubation between January 2014 and December 2018. INTERVENTIONS: None. MEASUREMENTS: The primary exposure was total propofol induction dose in mg/kg, and the primary outcome was occurrence of severe hypotension (MAP≤55 mmHg) prior to surgical incision, stratified by non-invasive vs. invasive blood pressure monitoring type. MAIN RESULTS: Among 320,585 total patients, 22.6% experienced the outcome of pre-incision severe hypotension (MAP≤55 mmHg). When stratified by blood pressure monitoring type, 20.7% with non-invasive blood pressure measurements, and 35.0% with invasive blood pressure measurements had the outcome. After controlling for a variety of patient and procedural factors, there was a significant independent association between propofol induction dose and pre-incision hypotension (Non-invasive blood pressure cohort odds ratio (OR) 1.10; 95% confidence interval (CI) 1.07 to 1.13; p < 0.001; and Invasive blood pressure cohort OR 1.15; 95%CI 1.10 to 1.21; adjusted p < 0.001). The association was robust to alternative definitions of the outcome, including less severe hypotension (MAP≤65 mmHg) and blood pressure drop from baseline as a continuous measure. Although no threshold safe induction dose was identified at which hypotension was avoided, an analysis of propofol dose greater or less than 1.5 mg/kg (i.e. the maximum FDA-defined typical induction dose) demonstrated that doses in excess of the FDAs threshold were positively associated with odds of severe hypotension (Non-invasive cohort: OR 1.05; 95% CI 1.02 to 1.08; p < 0.001; Invasive cohort: OR 1.11; 95%CI 1.05 to 1.17; adjusted p < 0.001). CONCLUSIONS: In a multicenter cohort of geriatric surgical patients receiving propofol for general anesthetic induction and endotracheal intubation, severe pre-incision hypotension (MAP ≤55 mmHg) that has previously been associated with postoperative morbidity was common. The dose of propofol used was significantly associated with increased odds of this outcome after controlling for a number of clinically relevant factors. Future studies that are designed to test different approaches to anesthesia induction for reducing severe post induction pre-incision hypotension are warranted.

Perioperative glycemic management in 2011: paradigm shifts.

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.

Variation in propofol induction doses administered to surgical patients over age 65.

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.

Scientific principles and clinical implications of perioperative glucose regulation and control.

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 <110 mg/dL). These results were quickly extrapolated to other clinical areas, and IGC was enthusiastically recommended in the perioperative period. However, there are few studies investigating the value of intraoperative glycemic control. Moreover, recent prospective trials have not been able to show the benefit of IGC; neither an appropriate therapeutic glycemic target nor the true efficacy of perioperative glycemic control has been fully determined. Practitioners should also appreciate technical nuances of various glucose measurement techniques. IGC increases the risk of hypoglycemia significantly, which is not inconsequential in critically ill patients. Until further specific data are accumulated, it is prudent to maintain glucose levels <180 mg/dL in the perioperative period, and glycemic control should always be accompanied by close glucose monitoring.

An Analysis of Anesthesia Induction Dosing in Female Older Adults.

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 US 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 (AKI). 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 had to be 65 years or older and to have 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 (standard deviation) age of the cohort was 72.20 (5.93) years. Regarding the primary outcome, 65.43% (354 patients, 95% confidence interval 61.2-69.4) of the cohort received more than the FDA recommended 1-1.5 mg/kg induction dose for patients of advanced age undergoing general anesthesia. RESULTS: The percentage of patients receiving doses in excess of the FDA guidance remained substantial across all age groups, but decreased progressively with increasing 5-year age intervals (from 74% among those aged 65-69 years to 44% among those aged > 80 years). 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 (4.1% [9/217] vs. 15.3% [21/138], p < 0.001), a result that may have been confounded by differential rates of missingness. CONCLUSIONS: Older adults commonly receive propofol induction doses in excess of the FDA guidance. The immediate hemodynamic effects of these doses on postinduction hypotension were not seen in the present cohort, suggesting that propofol dose adjustments may serve as a marker of physicians' judgments as to the frailty of patients. The relevance of the AKI association is difficult to interpret due to the non-differential missingness of AKI data between the two groups.

Preoperative beta-blocker use: impact of national guidelines on clinical practice.

STUDY OBJECTIVE: 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 (HR <60 beats per minute [bpm]). DESIGN: Retrospective, observational study. SETTING: Tertiary-care teaching hospital. MEASUREMENTS: 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. MAIN RESULTS: 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) (P < 0.01). 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). CONCLUSION: At our institution, preoperative beta-blocker use was not significantly changed by publication of the recommendations.

Safety of 4-factor prothrombin complex concentrate (4F-PCC) for emergent reversal of factor Xa inhibitors.

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.

Heparin displaces interferon-gamma-inducible chemokines (IP-10, I-TAC, and Mig) sequestered in the vasculature and inhibits the transendothelial migration and arterial recruitment of T cells.

BACKGROUND: Heparin, used clinically as an anticoagulant, also has antiinflammatory properties and has been described to inhibit interferon (IFN)-gamma responses in endothelial cells. We investigated the effects of heparin on the IFN-gamma-inducible chemokines IP-10/CXCL10, I-TAC/CXCL11, and Mig/CXCL9, which play important roles in the vascular recruitment of IFN-gamma-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-gamma or the IFN-gamma inducer interleukin-12. We confirmed previous reports that heparin inhibits the IFN-gamma-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-gamma 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.

Survey of anesthesiologists as to the value of prior ECG in a patient with nonspecific ST-T wave changes.

BACKGROUND: An abnormal ECG often must be assessed preoperatively in the absence of prior tracings. We surveyed anesthesiologists to determine if their concern about nonspecific ST-T (NSST) wave changes is influenced significantly by the availability of a prior ECG for comparison. METHODS: Forty-eight anesthesiologists rated their concern (O=none, 1=minor, 2=moderate, 3=marked) about a patient with an intermediate cardiac risk factor and new NSST, NSST of indeterminate duration (no old ECG for comparison), or old NSST. RESULTS: Concern for patients with more recent development of NSST was significantly greater for each of the interage comparisons; P=0.019 for new vs indeterminate, P=0.003 for new vs old, and P=0.008 for indeterminate vs old. This was associated with increased tendency to obtain cardiology consultation. CONCLUSIONS: The efficiency of preoperative assessment of patients with NSST on ECG would be improved by consistent availability of prior ECG tracings to enable determination of the newness of current findings.