High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

BACKGROUND: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS: Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS: The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.).

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

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

Effect of Volatile Anesthetics on Myocardial Infarction After Coronary Artery Surgery: A Post Hoc Analysis of a Randomized Trial.

OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG). DESIGN: A post hoc analysis of a randomized trial. SETTING: Cardiac surgical operating rooms. PARTICIPANTS: Patients undergoing elective, isolated CABG. INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes. MEASUREMENTS AND MAIN RESULTS: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03). CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.

Effect of volatile anesthetics on myocardial infarction after coronary artery surgery: a post hoc analysis of a randomized trial

OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG). DESIGN: A post hoc analysis of a randomized trial. SETTING: Cardiac surgical operating rooms. PARTICIPANTS: Patients undergoing elective, isolated CABG. INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes. Measurements and main Results: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03). CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.

Nitric oxide delivery during cardiopulmonary bypass reduces acute kidney injury: A randomized trial.

OBJECTIVE: Acute kidney injury (AKI) is a serious complication of cardiac surgery with cardiopulmonary bypass (CPB). The aim of this study was to evaluate the effects of nitric oxide (NO) supplementation to the CPB circuit on the development of cardiac surgery-associated AKI. METHODS: This prospective randomized controlled study included 96 patients with moderate risk of renal complications who underwent elective cardiac surgery with CPB. The study protocol was registered at ClinicalTrials.gov (identifier NCT03527381). Patients were randomly allocated to either NO supplementation to the CPB bypass circuit (NO treatment group; n = 48) or usual care (control group; n = 48). In the NO treatment group, 40-ppm NO was administered during the entire CPB period. The primary outcome was the incidence of AKI. RESULTS: NO treatment was associated with a significant decrease in AKI incidence (10 cases [20.8%] vs 20 cases [41.6%] in the control group; relative risk, 0.5; 95% confidence interval, 0.26-0.95; P = .023) and a higher median urine output during CPB (2.6 mL/kg/h [interquartile range (IQR), 2.1-5.08 mL/kg/h] vs 1.7 mL/kg/h [IQR, 0.80-2.50 mL/kg/h]; P = .0002). The median urinary neutrophil gelatinase-associated lipocalin level at 4 hours after surgery was significantly lower in the NO treatment group (1.12 ng/mL [IQR, 0.75-5.8 ng/mL] vs 4.62 ng/mL [IQR, 2.02-34.55 ng/mL]; P = .005). In the NO treatment group, concentrations of NO metabolites were significantly increased at 5 minutes postclamping, at 5 minutes after declamping, and at the end of the operation. Concentrations of proinflammatory and anti-inflammatory mediators and free plasma hemoglobin did not differ significantly between the 2 groups. CONCLUSIONS: NO administration in patients at moderate risk of renal complications undergoing elective cardiac surgery with CPB was associated with a lower incidence of AKI.

Volatile and Intravenous Anesthetics for Brain Protection in Cardiac Surgery: Does the Choice of Anesthesia Matter?

Postoperative neurologic complications have a significant effect on morbidity, mortality, and long-term disability in patients undergoing cardiac surgery. The etiology of brain injury in patients undergoing cardiac surgery is multifactorial and remains unclear. There are several perioperative causative factors for neurologic complications, including microembolization, hypoperfusion, and systemic inflammatory response syndrome. Despite technologic advances and the development of new anesthetic drugs, there remains a high rate of postoperative neurologic complications. Moreover, despite the strong evidence that volatile anesthesia exerts cardioprotective effects in patients undergoing cardiac surgery, the neuroprotective effects of volatile agents remain unclear. Several studies have reported an association of using volatile anesthetics with improvement of biochemical markers of brain injury and postoperative neurocognitive function. However, there is a need for additional studies to define the optimal anesthetic drug for protecting the brain in patients undergoing cardiac surgery.

Impact of malnutrition on survival in adult patients after elective cardiac surgery: Long-term follow up data.

The data article refers to the paper titles "Impact of malnutrition on long-term survival in adult patients after elective cardiac surgery" [1]. The data refer to the analysis of the relationship between baseline malnutrition and long-term mortality after cardiac surgery. Baseline demographic, nutritional, and medical history data were collected for each enrolled patient. Baseline serum albumin and C-reactive (CRP) protein levels were also obtained. Surgical risk was assessed in accordance with the logistic EuroSCORE. Intraoperative data including cardiopulmonary bypass (CPB) time and postoperative characteristics, such as postoperative complications, number of days in the ICU, and hospitalization duration, were also collected. Data on nutritional status were collected using four nutritional screening tools: (1) malnutrition universal screening tool (MUST), (2) short nutritional assessment questionnaire (SNAQ), (3) mini-nutritional assessment (MNA), and (4) nutritional risk screening 2002 (NRS-2002). Both electronic medical records and phone interviews were used for survival data collection. ROC analysis was performed to analyze prognostic value of baseline and perioperative variables on long-term mortality. Univariate and multivariate logistic regression analysis of predictors of 3- and 8-year mortality were performed. Kaplan-Meyer curves, describing the impact of baseline and perioperative characteristics on 3- and 8-year survival were also performed.

Effects of malnutrition on long-term survival in adult patients after elective cardiac surgery.

OBJECTIVES: The aim of this study was to investigate the relationship between malnutrition and long-term survival in patients who underwent cardiopulmonary bypass (CPB). METHODS: This study analyzed the long-term survival data of a mixed cohort of 1187 cardiac patients previously enrolled in a prospective observational study of nutritional screening in cardiac surgery. Nutritional status was assessed using the Malnutrition Universal Screening Tool (MUST). The mean age of patients was 58.86 ± 10.07 y (95% confidence interval [CI], 58.2-59.4). The median time of follow-up was 73.4 mo (25th-75th percentiles, 18.3-101.3). RESULTS: In all, 449 patients (37.8%) were lost to follow-up after hospitalization. For the remaining participants, the overall 8-y survival was 68% (95% CI, 59-76) and 77% (95% CI, 73-80; log-rank, P = 0.12) in patients with and without malnutrition risk, respectively. Statistically significant differences in survival were found during the 3-y follow-up of patients with heart valve disease: 83% (95% CI, 74-92) with malnutrition versus 93% (95% CI, 90-96) without malnutrition (log-rank, P = 0.03). The final multivariate Cox regression model revealed logistic EuroSCORE (hazard ratio (HR), 1.337; 95% CI, 1.110-1.612), cardiopulmonary bypass time <110.5 min (HR 0.463, 95% CI 0.255-0.842), preoperative albumin (HR 0.799, 95% CI 0.691-0.924), and C-reactive protein (HR, 1.106; 95% CI, 1.018-1.202) as independent predictors of 3-y survival. CONCLUSION: Preoperative malnutrition is not associated with 8-y mortality in a mixed cardiac surgery cohort. However, it may be associated with worse 3-y outcomes in patients with heart valve disease.

Brain Oxygen Supply in Older Adults During Coronary Artery Bypass Grafting.

OBJECTIVES: To evaluate the dynamics of the cerebral oxygen supply in patients aged ≥65 years, during coronary artery bypass grafting (CABG), and to test the hypothesis that lower intraoperative brain oxygen saturation is associated with postoperative neurological complications. DESIGN: Prospective cohort study. SETTING: The E. Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation, Novosibirsk, Russia. PARTICIPANTS: The study comprised 200 elderly patients who underwent CABG between April, 2018 and November, 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The regional hemoglobin oxygen saturation (rSO2, %) of the right and left brain hemispheres were assessed during the intraoperative period using bilateral near-infrared spectroscopy. Furthermore, neurological complications during hospitalization were evaluated. At the anesthesia induction stage, the average levels of rSO2 for the right and left hemispheres were within 65% and did not differ significantly at any stage of CABG (p>0.05). The risk of neurological complications was associated with rSO2 decrease during cardiopulmonary bypass (CPB). An increased risk was associated with rSO2 decrease by 20% or more during CPB, relative to the stage of anesthesia induction, which was observed in 19% of patients. CONCLUSIONS: In elderly patients, the decrease in rSO2 during CPB is associated with an increased risk of neurological complications during hospitalization. This risk increases with a decrease in rSO2 by 20% or more during CPB relative to the stage of anesthesia induction, by a 5-fold and 7-fold for the left and right hemispheres, respectively.

Long-term outcome of perioperative low cardiac output syndrome in cardiac surgery: 1-year results of a multicenter randomized trial.

PURPOSE: Perioperative myocardial dysfunction occurs frequently in cardiac surgery, and is a risk factor for morbidity and mortality. Levosimendan has been suggested to reduce mortality of patients with perioperative myocardial dysfunction. However, long-term outcome data on its efficacy in cardiac surgery are lacking. MATERIALS AND METHODS: Cardiac surgery patients with perioperative myocardial dysfunction were randomized to levosimendan or placebo, in addition to standard inotropic care. One-year mortality data were collected. RESULTS: We randomized 506 patients (248 to levosimendan 258 to placebo). At 1-year follow-up, 41 patients (16.5%) died in the levosimendan group, while 47 (18.3%) died in the placebo group (absolute risk difference -1.8; 95% CI -8.4 to 4.9; P = .60). Female sex, history of chronic obstructive pulmonary disease, previous myocardial infarction, serum creatinine, hematocrit, mean arterial pressure, and duration of cardiopulmonary bypass were independently associated with 1-year mortality. CONCLUSIONS: Levosimendan administration does not improve 1-year survival in cardiac surgery patients with perioperative myocardial dysfunction. One-year mortality in these patients is 17%. Six predictive factors for long-term mortality were identified. STUDY REGISTRATION NUMBER: NCT00994825 (ClinicalTrials.gov).

Long-term health-related quality of life after surgery in patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: To assess the dynamic of various health-related quality of life (HRQoL) parameters 3 years after pulmonary thromboendarterectomy (PTE), and to identify factors affecting HRQoL parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH) in the long-term follow-up after surgery. METHODS: This prospective cohort study included 128 patients with CTEPH before and after the PTE (3 year follow-up). The HRQoL was examined using the Short-Form 36 Health Survey Questionnaire (SF-36). RESULTS: In patients with CTEPH 3 years after PTE, a significant improvement in all the HRQoL parameters. The summary indicators of the physical and mental components of health remained at the same level as 1 year after the PTE and did not exceed 50 points. The residual pulmonary hypertension was a leading factor limiting parameters of physical and mental health 3 years after a PTE. In addition, the parameters of physical activity were adversely affected by age and the age-adjusted Charlson Comorbidity Index. CONCLUSIONS: In the study group of patients with CTEPH, PTE contributes to a significant improvement in all HRQoL parameters, which observed both 1 year and 3 years after surgery. The leading factor adversely affecting the physical and emotional components of health in the long-term period after PTE was residual pulmonary hypertension recorded in the early postoperative period. In addition, some physical HRQoL parameters are affected by age and age-adjusted Charlson Comorbidity Index.

Current Practice of Calcium Use During Cardiopulmonary Bypass Weaning: Results of an International Survey.

OBJECTIVES: To describe international practices on the use of calcium salts during cardiopulmonary bypass (CPB) weaning in adult cardiac surgery patients. DESIGN: Multiple-choice survey on current practice of CPB weaning. SETTING: Online survey using the SurveyMonkey platform. PARTICIPANTS: Departments of cardiac anesthesiology worldwide. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 112 surveys sent, 100 centers from 32 countries replied. The majority of centers (88 of 100 = 88%) administer calcium salts intraoperatively: 71 of 100 (71%) are using these drugs for CPB weaning and 78 of 100 (78%) for correction of hypocalcemia. Among the 88 centers that use calcium salts intraoperatively, 66% (58 of 88) of respondents use calcium chloride, 22% (19 of 88) use calcium gluconate, and 12% (11 of 88) use both drugs. Calcium salts are routinely used during normal (47 of 71 centers = 66%) and difficult (59 of 71 centers = 83%) weaning from CPB. Doses of 5 to 15 mg/kg during termination of CPB were used by 55 of 71 centers (77%) either by bolus (39 of 71, 55%) or over a time period longer than 1 minute (32 of 71 = 45%). Norepinephrine is the most commonly used first line vasopressor or inotropic agent used to support hemodynamics during termination of CPB in 32 out of 100 centers (32%), and calcium is the second one, used by 23 out of 100 centers (23%). CONCLUSION: This survey demonstrates that the majority of cardiac centers use calcium in adult patients undergoing cardiac surgery, especially during weaning from CPB. There is variability on the type of drug, dose, and modality of drug administration.

Calcium Administration During Weaning From Cardiopulmonary Bypass: A Narrative Literature Review.

The search for safe and effective patient management strategies during weaning from cardiopulmonary bypass is ongoing; intravenous calcium is occasionally used as a first-line drug. The physiologic role of calcium suggests that it can support the function of the cardiovascular system during this critical period. Patients may be mildly hypocalcemic after cardiopulmonary bypass; however, this degree of hypocalcemia does not significantly impair the cardiovascular system. The transient beneficial effects of calcium administration (increase in arterial blood pressure, systemic vascular resistance, cardiac index, stroke volume, and coronary perfusion pressure) might be helpful in cases of moderate contractility reduction or vasoplegia. Nonetheless, effects on clinically relevant endpoints are unknown, and possible systemic side effects, such as transient reduction in internal mammary artery graft flow, attenuation of the effects of ß-sympathomimetics, "stone heart" phenomenon, and pancreatic cellular injury, may limit the use of calcium salts. Further studies are needed to expand the understanding of the effects of calcium administration on patient outcomes.

Sustained High-dose Thiamine Supplementation in High-risk Cardiac Patients Undergoing Cardiopulmonary Bypass: A Pilot Feasibility Study (The APPLY trial).

OBJECTIVE: To test the feasibility and investigate possible cardiovascular effects of a sustained high-dose intravenous thiamine protocol in patients undergoing combined valvular and coronary artery bypass graft surgery. DESIGN: Randomized, placebo-controlled, pilot feasibility trial. SETTING: Cardiac surgery department of a tertiary hospital. PARTICIPANTS: Forty patients undergoing combined valvular and coronary artery bypass surgery. INTERVENTIONS: Intravenous thiamine (600 mg on the day of surgery, and 400 mg/day on postoperative days 1, 2, and 3) or placebo. MEASUREMENTS AND MAIN RESULTS: The primary feasibility endpoints were recruitment rate and protocol compliance. Secondary endpoints included markers of possible biological and physiological effects. The mean recruitment rate was 8 patients per month and protocol compliance was 97.5%. There were no differences in median peak postoperative lactate (2.7 mmol/L [interquartile range [IQR] 1.4-4.6] for thiamine v 2.5 mmol/L [IQR 1.4-3.6] for placebo; p = 0.53), median peak postoperative creatinine (104 µmol/L [IQR 92.5-129] for thiamine v 99 µmol/L [IQR 86.5-109.5] for placebo; p = 0.53), median nadir postoperative cardiac index (1.8 L/min/m2 [IQR 1.5-2.1] for thiamine v 2.2 L/min/m2 [IQR 1.5-2.5] for placebo; p = 0.25), or the number of patients on vasopressor/inotropic agents (thiamine, 12 [63%]; placebo, 12 [60%]; p = 0.80), or in the total inotrope/vasopressor dose 0.14 µg/kg for thiamine v 0.12 µg/kg for placebo; p = 0.88). CONCLUSIONS: A double-blind trial of sustained high-dose intravenous thiamine supplementation in higher-risk cardiac surgery patients was feasible and appeared to be safe. However, such treatment did not demonstrate evidence of biological or physiological effects.

The Clinical Outcomes in Patients with Critical Limb Ischemia One Year after Spinal Cord Stimulation.

BACKGROUND: The aim of this study was to evaluate the long-term outcomes of spinal cord stimulation in patients with critical limb ischemia and to test the hypothesis that the dynamics of clinical changes one year after therapy depend both on the clinical determinants associated with the underlying disease and on factors related to systemic atherosclerosis. METHODS: This prospective cohort study included 56 patients with critical limb ischemia. All patients before and after spinal cord stimulation were examined in terms of the dynamics of their clinical changes using the Rutherford scale and transcutaneous oxygen tension (TcPO2, mm Hg) in the affected foot. The active orthostatic test was used to assess the functional state of peripheral perfusion. RESULTS: One year after spinal cord stimulation, 74% of patients showed positive clinical outcomes. No changes were observed in 9.3% of patients, whereas adverse clinical outcomes were revealed in 16.7% of cases. The TcPO2 values were significantly reduced before spinal cord stimulation: 10.5 (6.4-16.0) mm Hg. The functional status of the peripheral microvasculature was also disturbed. One year after therapy, TcPO2 significantly increased and the adaptive mechanisms of the microvasculature were improved in more than 70% of patients. Logistic regression analysis showed that the initially low TcPO2 values (<10 mm Hg) with a lack of gain in TcPO2 during the orthostatic test are associated with the negative clinical outcomes after spinal cord stimulation. The gain in TcPO2 during the orthostatic test to >10 mm Hg is associated with the positive clinical outcomes after spinal cord stimulation. The age-adjusted Charlson Comorbidity Index >5 and duration of critical ischemic symptoms also had a negative effect on the clinical outcomes after spinal cord stimulation. CONCLUSIONS: The positive clinical outcomes were revealed in most patients with critical limb ischemia one year after spinal cord stimulation. The low values of peripheral tissue metabolism with the disturbed functional status of the microvasculature are associated with the negative clinical outcome. The patients with baseline TcPO2 <10 mm Hg can recover if they still have a sufficient microcirculatory reserve capacity. Duration of critical ischemic symptoms and high comorbidity burden with allowance for age are negative factors affecting the clinical outcome.

Adrenergic Downregulation in Critical Care: Molecular Mechanisms and Therapeutic Evidence.

Catecholamines remain the mainstay of therapy for acute cardiovascular dysfunction. However, adrenergic receptors quickly undergo desensitization and downregulation after prolonged stimulation. Moreover, prolonged exposure to high circulating catecholamines levels is associated with several adverse effects on different organ systems. Unfortunately, in critically ill patients, adrenergic downregulation translates into progressive reduction of cardiovascular response to exogenous catecholamine administration, leading to refractory shock. Accordingly, there has been a growing interest in recent years toward use of noncatecholaminergic inotropes and vasopressors. Several studies investigating a wide variety of catecholamine-sparing strategies (eg, levosimendan, vasopressin, ß-blockers, steroids, and use of mechanical circulatory support) have been published recently. Use of these agents was associated with improvement in hemodynamics and decreased catecholamine use but without a clear beneficial effect on major clinical outcomes. Accordingly, additional research is needed to define the optimal management of catecholamine-resistant shock.

The "Ice Age" in Cardiac Surgery: Evolution of the "Siberian" Method of Brain Protection During Deep Hypothermic Perfusionless Circulatory Arrest.

Deep hypothermic perfusionless circulatory arrest was the first practical neuroprotective technique used for open-heart surgery. It was refined at the Novosibirsk Medical Research Center in Siberia and was actively used from the mid-1950s until 2001.This review describes the development of this technique and its contribution to our understanding of the dynamic changes in human physiology during induced hypothermia for circulatory arrest without extracorporeal perfusion. Deep hypothermic perfusionless circulatory arrest was an important stepping stone in the development of modern approaches in neuroprotection and monitoring during cardiac surgery.