domingo, 9 de novembro de 2008

Anemia and Cerebral Outcomes: Many Questions, Fewer Answers.

Title Anemia and Cerebral Outcomes: Many Questions, Fewer Answers.[Review]

Source Anesthesia & Analgesia. 107(4):1356-1370, October 2008.

Abstract A number of clinical studies have associated acute anemia with cerebral injury in perioperative patients. Evidence of such injury has been observed near the currently accepted transfusion threshold (hemoglobin [Hb] concentration, 7-8 g/dL), and well above the threshold for cerebral tissue hypoxia (Hb 3-4 g/dL). However, hypoxic and nonhypoxic mechanisms of anemia-induced cerebral injury have not been clearly elucidated. In addition, protective mechanisms which may minimize cerebral injury during acute anemia have not been well defined. Vasodilatory mechanisms, including nitric oxide (NO), may help to maintain cerebral oxygen delivery during anemia as all three NO synthase (NOS) isoforms (neuronal, endothelial, and inducible NOS) have been shown to be up-regulated in different experimental models of acute hemodilutional anemia. Recent experimental evidence has also demonstrated an increase in an important transcription factor, hypoxia inducible factor (HIF)-1[alpha], in the cerebral cortex of anemic rodents at clinically relevant Hb concentrations (Hb 6-7 g/dL). This suggests that cerebral oxygen homeostasis may be in jeopardy during acute anemia. Under hypoxic conditions, cytoplasmic HIF-1[alpha] degradation is inhibited, thereby allowing it to accumulate, dimerize, and translocate into the nucleus to promote transcription of a number of hypoxic molecules. Many of these molecules, including erythropoietin, vascular endothelial growth factor, and inducible NOS have also been shown to be up-regulated in the anemic brain. In addition, HIF-1[alpha] transcription can be increased by nonhypoxic mediators including cytokines and vascular hormones. Furthermore, NOS-derived NO may also stabilize HIF-1[alpha] in the absence of tissue hypoxia. Thus, during anemia, HIF-1[alpha] has the potential to regulate cerebral cellular responses under both hypoxic and normoxic conditions. Experimental studies have demonstrated that HIF-1[alpha] may have either neuroprotective or neurotoxic capacity depending on the cell type in which it is up-regulated. In the current review, we characterize these cellular processes to promote a clearer understanding of anemia-induced cerebral injury and protection. Potential mechanisms of anemia-induced injury include cerebral emboli, tissue hypoxia, inflammation, reactive oxygen species generation, and excitotoxicity. Potential mechanisms of cerebral protection include NOS/NO-dependent optimization of cerebral oxygen delivery and cytoprotective mechanisms including HIF-1[alpha], erythropoietin, and vascular endothelial growth factor. The overall balance of these activated cellular mechanisms may dictate whether or not their up-regulation leads to cytoprotection or cellular injury during anemia. A clearer understanding of these mechanisms may help us target therapies that will minimize anemia-induced cerebral injury in perioperative patients.

Pulmonary Cytokine Responses During Mechanical Ventilation of Noninjured Lungs With and Without End-Expiratory Pressure.

Title Pulmonary Cytokine Responses During Mechanical Ventilation of Noninjured Lungs With and Without End-Expiratory Pressure.[Miscellaneous Article]

Source Anesthesia & Analgesia. 107(4):1265-1275, October 2008.

Abstract BACKGROUND: Positive end-expiratory pressure (PEEP) during mechanical ventilation may impose different degrees of stress on healthy lungs. On the assumption that stress is reflected by cytokine production, we performed a translational study investigating the effect of PEEP on bronchoalveolar and systemic mediator levels in isolated perfused mouse lungs (IPL) and in patients with healthy lungs.

METHODS: (Part I) IPL were ventilated with end-expiratory pressures of 0, 3, 6, or 10 cm H2O and end-inspiratory pressure (EIP) levels of 10 or 25 cm H2O. Interleukin (IL)-6 and macrophage inflammatory protein-2 concentrations in the venous effluate were monitored. (Part II) Patients (nonsmokers) scheduled for elective otorhinolaryngology surgery (duration >90 min) were randomized to receive either ventilation with zero end-expiratory pressure or PEEP (10 cm H2O). Mediators in bronchoalveolar lavage, nuclear factor [kappa]B, (NF-[kappa]B)-activation in alveolar macrophages and circulating systemic mediators were monitored. Control patients underwent bronchoalveolar lavage after intubation.

RESULTS: In the IPL, mediator concentrations increased with increasing end-expiratory pressure at an EIP of 10 cm H2O, but decreased at 25 cm H2O EIP. In patients, bronchoalveolar IL-6, monocyte chemoattractant protein-1, and granulocyte monocyte-colony stimulating factor were increased by ventilation regardless of the PEEP level. IL-6 and IL-8 levels were moderately increased by PEEP but not zero end-expiratory pressure. Nuclear factor [kappa]B DNA binding activity in alveolar macrophages and systemic mediator levels did not change.

CONCLUSIONS: On the basis of the premise that cytokine levels may indicate mechanical stress, our findings indicate that even low tidal volume ventilation causes some stress. PEEP is beneficial at high inspiratory pressure, but imposes moderate stress at low inspiratory pressure.

Moderate Acute Isovolemic Hemodilution Alters Myocardial Function in Patients with Coronary Artery Disease.

Moderate Acute Isovolemic Hemodilution Alters Myocardial Function in Patients with Coronary Artery Disease.[Miscellaneous Article]

Source Anesthesia & Analgesia. 107(4):1145-1152, October 2008.

Abstract BACKGROUND: Although moderate hemodilution is usually well tolerated in coronary artery surgery patients, this may not be the case when myocardial oxygen demand is increased. We hypothesized that, in these patients, hemodilution in the presence of an increased heart rate could be associated with an impairment of myocardial function.

METHODS: Forty coronary surgery patients were randomly assigned to two groups (n = 20), according to the rate of atrioventricular pacing [70 bpm (Group 70) or 90 bpm (Group 90)]. While paced at the fixed heart rate, hemodilution was performed before the start of cardiopulmonary bypass. Data were obtained from a pulmonary artery, a PiCCO catheter and a left ventricular pressure catheter. Measurements were obtained in steady-state conditions before and after isovolemic hemodilution.

RESULTS: Hemodilution from 40% +/- 2% to 30% +/- 1% in Group 70, and from 39% +/- 4% to 30% +/- 2% in Group 90 resulted in a decrease in systemic vascular resistance and an increase in end-diastolic volume in both groups. This was associated with an increase in stroke volume in Group 70 but not in Group 90. In this latter group, the maximal rate of pressure development decreased significantly after hemodilution [from 856 +/- 93 to 716 +/- 80 mm Hg/s (P < 0.01)], whereas it remained unchanged in Group 70 (843 +/- 86 mm Hg/s before and 832 +/- 79 mm Hg/s after hemodilution).

CONCLUSIONS: In the conditions of the present study, increased heart rate during moderate hemodilution was associated with a depression of myocardial function.

Pulse Pressure and Risk of Adverse Outcome in Coronary Bypass Surgery.

Title Pulse Pressure and Risk of Adverse Outcome in Coronary Bypass Surgery.[Miscellaneous Article]

Source Anesthesia & Analgesia. 107(4):1122-1129, October 2008.

Abstract BACKGROUND: Among ambulatory patients, an increase in pulse pressure (PP) is a well-established determinant of vascular risk. The relationship of PP and acute perioperative vascular outcome among patients having coronary artery bypass graft (CABG) surgery is less well known.

METHODS: We conducted a prospective observational study involving 5436 patients having elective CABG surgery requiring cardiopulmonary bypass. Of these, 4801 met final inclusion criteria. Comprehensive data were captured for medical history, intraoperative and postoperative physiologic and laboratory measures, diagnostic testing, and clinical events. The relationship between preoperative hypertension (systolic, diastolic, PP) and ischemic cardiac and cerebral outcomes and death was assessed using multivariable logistic regression; P < 0.05 was considered significant.

RESULTS: Nine hundred and seventeen patients (19.1%) had fatal and nonfatal vascular complications, including 146 patients (3.0%) with cerebral and 715 patients (14.9%) with cardiac events. In-hospital mortality occurred in 147 patients (3.1%). Among all blood pressure variables measured preoperatively, PP was most strongly associated with an increased risk of postoperative complications. PP increments of 10 mm Hg (above a threshold of 40 mm Hg) were associated with an increased risk of cerebral events (adjusted odds ratio: 1.12; 95% CI [1.002-1.28]; P = 0.026). The incidence of a cerebral event and/or death from neurologic complications nearly doubled for patients with PP >80 mm Hg versus <=80 mm Hg (5.5% vs 2.8%; P = 0.004). PP more than 80 mm Hg was also found to be associated with cardiac complications, increasing the incidence of congestive heart failure by 52%, and death from cardiac cause by nearly 100% (P = 0.003 and 0.006, respectively).

CONCLUSION: An increase in PP was independently and significantly associated with greater fatal and nonfatal adverse cerebral and cardiac outcomes in patients having CABG surgery. These findings highlight the associated risks of preoperative PP on acute postoperative vascular outcomes.

The ECLIPSE Trials: Comparative Studies of Clevidipine to Nitroglycerin, Sodium Nitroprusside, and Nicardipine for Acute Hypertension Treatment in Car

Title The ECLIPSE Trials: Comparative Studies of Clevidipine to Nitroglycerin, Sodium Nitroprusside, and Nicardipine for Acute Hypertension Treatment in Cardiac Surgery Patients.[Miscellaneous Article]

Source Anesthesia & Analgesia. 107(4):1110-1121, October 2008.

Abstract BACKGROUND: Acute hypertension during cardiac surgery can be difficult to manage and may adversely affect patient outcomes. Clevidipine is a novel, rapidly acting dihydropyridine L-type calcium channel blocker with an ultrashort half-life that decreases arterial blood pressure (BP). The Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events trial (ECLIPSE) was performed to compare the safety and efficacy of clevidipine (CLV) with nitroglycerin (NTG), sodium nitroprusside (SNP), and nicardipine (NIC) in the treatment of perioperative acute hypertension in patients undergoing cardiac surgery.

METHODS: We analyzed data from three prospective, randomized, open-label, parallel comparison studies of CLV to NTG or SNP perioperatively, or NIC postoperatively in patients undergoing cardiac surgery at 61 medical centers. Of the 1964 patients enrolled, 1512 met postrandomization inclusion criteria of requiring acute treatment of hypertension based on clinical criteria. The patients were randomized 1:1 for each of the three parallel comparator treatment groups. The primary outcome was the incidence of death, myocardial infarction, stroke or renal dysfunction at 30 days. Adequacy and precision of BP control was evaluated and is reported as a secondary outcome.

RESULTS: There was no difference in the incidence of myocardial infarction, stroke or renal dysfunction for CLV-treated patients compared with the other treatment groups. There was no difference in mortality rates between the CLV, NTG or NIC groups. Mortality was significantly higher, though, for SNP-treated patients compared with CLV-treated patients (P = 0.04). CLV was more effective compared with NTG (P = 0.0006) or SNP (P = 0.003) in maintaining BP within the prespecified BP range. CLV was equivalent to NIC in keeping patients within a prespecified BP range; however, when BP range was narrowed, CLV was associated with fewer BP excursions beyond these BP limits compared with NIC.

CONCLUSIONS: CLV is a safe and effective treatment for acute hypertension in patients undergoing cardiac surgery.

Dexmedetomidine: A Novel Drug for the Treatment of Atrial and Junctional Tachyarrhythmias During the Perioperative Period for Congenital Cardiac Surge

Title Dexmedetomidine: A Novel Drug for the Treatment of Atrial and Junctional Tachyarrhythmias During the Perioperative Period for Congenital Cardiac Surgery: A Preliminary Study.[Miscellaneous Article]

Source Anesthesia & Analgesia. 107(5):1514-1522, November 2008.

Abstract BACKGROUND: Atrial and junctional tachyarrhythmias occur frequently during the perioperative period for congenital cardiac surgery and can be a cause of increased morbidity and mortality. These rhythm disturbances that may be well tolerated in a normal heart can cause significant hemodynamic instability in patients with congenital heart defects, particularly during the postcardiopulmonary bypass period. Management of these arrhythmias presents more of a challenge, since currently available antiarrhythmic drugs can be ineffective and poorly tolerated. In this study, we examined the possible effect of dexmedetomidine, a primarily sedative drug, on atrial and junctional tachyarrhythmias. Though some animal data have shown that it can prevent certain types of ventricular tachycardia, its therapeutic role during these types of arrhythmias has not been studied.

METHODS: This was a retrospective, nonrandomized, noncontrolled study. Fourteen patients admitted to the cardiac intensive care unit and who received dexmedetomidine for both, sedation/analgesia and for junctional ectopic tachycardia (JET), atrial ectopic tachycardia (AET), reentry type supraventricular tachycardia (Re-SVT), atrial flutter (AF) or junctional accelerated rhythm (JAR) were included. Dexmedetomidine was used as a primary drug or as a rescue if other antiarrhythmics had been used. Our primary end-points were (a) conversion to normal sinus rhythm (NSR) within 3 min for Re-SVT, and 2 h for all other arrhythmias or (b) heart rate (HR) reduction to improve hemodynamics; JET <=170 bpm, AET >=20%, AF <=150 bpm and for JAR prevention of progression to JET.

RESULTS: The mean age and weight were 2 +/- 3 mo and 4 +/- 1.5 kg, respectively. Most of the arrhythmias (79%) occurred during the postoperative period. Dexmedetomidine was used as a primary treatment in nine and as a rescue in five patients. Ten patients (71%) received an initial loading dose of 1.1 +/- 0.5 [mu]g/kg. A continuous infusion, 0.9 +/- 0.3 [mu]g [middle dot] kg-1 [middle dot] h-1 was administered in 12 patients. Thirteen patients' lungs were mechanically ventilated. Adverse effects were seen in four patients (28%). Three had hypotension that responded to fluid administration and one had a possible brief complete atrioventricular (AV) block. Nine of the 14 patients were transiently paced with atrial (seven) or AV sequential (two) pacing to improve AV synchrony. The primary outcome with rhythm and/or HR control was achieved in 13 patients (93%). JET rate decreased from 197 +/- 22 to 165 +/- 17 bpm within 67 +/- 75 min of dexmedetomidine administration. Five of these patients converted to NSR in 39 +/- 31 h and one remained in JAR. All four patients with Re-SVT had resolution of their tachyarrhythmia. Three converted to NSR and one to JAR. One patient with AET (220-270 bpm) responded well with decreasing HR to 120 bpm within 35 min and to NSR in 85 min. One patient with AF failed to respond. In two patients with JAR, neither progressed to JET and HR decreased from 158 +/- 11 to 129 +/- 1 bpm.

CONCLUSION: This preliminary, observational report suggests that dexmedetomidine may have a potential therapeutic role in the acute phase of perioperative atrial and junctional tachyarrhythmias for either HR control or conversion to NSR.

(C) 2008 by International Anesthesia Research Society.

A Randomized Controlled Trial of Cell Salvage in Routine Cardiac Surgery.

Title A Randomized Controlled Trial of Cell Salvage in Routine Cardiac Surgery.[Miscellaneous Article]

Source Anesthesia & Analgesia. 107(5):1487-1495, November 2008.

Abstract BACKGROUND: Previous trials have indicated that cell salvage may reduce allogeneic blood transfusion during cardiac surgery, but these studies have limitations, including inconsistent use of other blood transfusion-sparing strategies. We designed a randomized controlled trial to determine whether routine cell salvage for elective uncomplicated cardiac surgery reduces blood transfusion and is cost effective in the setting of a rigorous transfusion protocol and routine administration of antifibrinolytics.

METHODS: Two-hundred-thirteen patients presenting for first-time coronary artery bypass grafting and/or cardiac valve surgery were prospectively randomized to control or cell salvage groups. The latter group had blood aspirate during surgery and mediastinal drainage the first 6 h after surgery processed in a cell saver device and autotransfused. All patients received tranexamic acid and were subjected to an algorithm for red blood cell and hemostatic blood factor transfusion.

RESULTS: There was no difference between the two groups in the proportion of patients exposed to allogeneic blood (32% in both groups, relative risk 1.0 P = 0.89). At current blood products and cell saver prices, the use of cell salvage increased the costs per patient by a minimum of $103. When patients who had mediastinal re-exploration for bleeding were excluded (as planned in the protocol), significantly fewer units of allogeneic red blood cells were transfused in the cell salvage compared with the control group (65 vs 100 U, relative risk 0.71 P = 0.04).

CONCLUSION: In patients undergoing routine first-time cardiac surgery in an institution with a rigorous blood conservation program, the routine use of cell salvage does not further reduce the proportion of patients exposed to allogeneic blood transfusion. However, patients who do not have excessive bleeding after surgery receive significantly fewer units of blood with cell salvage. Although the use of cell savage may reduce the demand for blood products during cardiac surgery, this comes at an increased cost to the institution.

(C) 2008 by International Anesthesia Research Society.

DOI Number 10.1213/ane.0b013e3181831e54

Tranexamic Acid and Aprotinin in Primary Cardiac Operations: An Analysis of 220 Cardiac Surgical Patients Treated with Tranexamic Acid or Aprotinin.

Title Tranexamic Acid and Aprotinin in Primary Cardiac Operations: An Analysis of 220 Cardiac Surgical Patients Treated with Tranexamic Acid or Aprotinin.[Miscellaneous Article]

Source Anesthesia & Analgesia. 107(5):1469-1478, November 2008.

Abstract BACKGROUND: Antifibrinolytics are widely used in cardiac surgery to reduce bleeding. Allogeneic blood transfusion, even in primary cardiac operations with low blood loss, is still high. In the present study we evaluated the impact of tranexamic acid compared to aprotinin on the transfusion incidence in cardiac surgical patients with low risk of bleeding.

METHODS: This prospective, randomized, double-blind study included 220 patients undergoing primary coronary artery revascularization (coronary artery bypass grafting [CABG]) or aortic valve replacement (AVR). Randomized in blocks of 20, patients received either tranexamic acid (approximately 6 g) or full-dose aprotinin (approximately 5-6 x 106 Kallikrein Inhibiting Units). Transfusion was guided by a strict transfusion algorithm. Molecular markers of hemostasis were determined to assess differences in the mode of action of the two drugs. Primary end-points were the incidence of allogeneic red cell transfusion and 24-h postoperative blood loss. Data were analyzed according to the intention-to-treat principle and compared using the [chi]2 and Mann-Whitney U-test.

RESULTS: Two-hundred-twenty patients were enrolled (CABG: 134, AVR: 86). In the aprotinin Group 47% of patients received allogeneic blood during the hospital stay as compared to 61% in the tranexamic acid group (P = 0.036). Aprotinin conferred a 23% reduction in allogeneic transfusion risk (RR 0.77, 95% CI 0.53-0.88). Overall, no significant difference in postoperative bleeding was observed, although 24-h blood loss was reduced in aprotinin-treated CABG patients (500, 350-750 mL vs 650, 475-875 mL (median, 25th-75th percentile); P = 0.039). Despite the lower transfusion rate, the hemoglobin concentration on the first postoperative day was higher in the aprotinin group (11.3, 9.9-12.1 vs 10.6, 9.9-11.6 mg/dL; P = 0.023). The fibrinolytic activity at the end of operation determined by D-Dimer was comparable in both groups. (0.15, 0.11-0.17 mg/L [aprotinin] versus 0.18, 0.12-0.24 mg/L [tranexamic acid]). The activated partial thromboplastin time was prolonged up to 4 h postoperatively in the aprotinin group, while the heparin requirement was reduced: 19% of the patients in the aprotinin group and 45% in the tranexamic acid group received at least one additional bolus heparin during cardiopulmonary bypass (P < 0.001). Troponin T levels postoperatively and on postoperative day 1 were significantly higher in the tranexamic acid group (P = 0.017). No differences in renal, cardiac, or mortality outcomes were observed.

CONCLUSION: Considering the rate of transfusion of red blood cells, tranexamic acid was slightly inferior in patients undergoing CABG, but there was no difference in patients receiving AVR. Tranexamic acid seems to be less effective in operations with increased bleeding such as CABG. Clinical benefit depends on specific patient and institution characteristics ( ClinicalTrials.gov NCT00396760).

(C) 2008 by International Anesthesia Research Society.

DOI Number 10.1213/ane.0b013e318182252b

A Thromboelastometric Evaluation of the Effects of Hypothermia on the Coagulation System.

Title A Thromboelastometric Evaluation of the Effects of Hypothermia on the Coagulation System.[Miscellaneous Article]

Source Anesthesia & Analgesia. 107(5):1465-1468, November 2008.

Abstract BACKGROUND: Hypothermia may be accidental or therapeutic. Therapeutic hypothermia is increasingly used as treatment for various conditions, e.g., neuroprotection after cardiac arrest. Hypothermia leads to an impairment of the coagulation system, but the degree of impairment has been difficult to determine. Most studies have been performed on plasma instead of whole blood. We therefore evaluated whole blood investigating the effects of hypothermia on the coagulation system over a wide range of temperatures (25-40[degrees]C).

METHODS: Blood was drawn from six healthy volunteers into citrated test tubes. Samples were then placed in water baths with temperatures ranging from 25 to 40[degrees]C for 30 min before the coagulation system was studied using rotational thromboelastometry. A contact activator (Ellagic acid) was used for initiation of coagulation. Clotting time, clot formation time, [alpha] angle, and maximum clot strength were measured. All tests were run for 60 min and they were performed at the same temperature as the temperature in the water bath.

RESULTS: Coagulation was increasingly impaired with decreasing temperatures in the temperature range studied. All variables measured were significantly impaired in a stepwise pattern (P < 0.0001).

CONCLUSIONS: Evaluation using a whole blood analysis shows that hypothermia progressively impairs the coagulation system.

(C) 2008 by International Anesthesia Research Society.

DOI Number 10.1213/ane.0b013e31817ee955

The effects of interrupted or continuous administration of sevoflurane on preconditioning before cardio-pulmonary bypass in coronary artery surgery: c

The effects of interrupted or continuous administration of sevoflurane on preconditioning before cardio-pulmonary bypass in coronary artery surgery: comparison with continuous propofol.[Article]

Source Anaesthesia. 63(10):1046-1055, October 2008.

Abstract Summary: Volatile anaesthetics have been shown to exert cardioprotective properties in experimental and clinical studies. However, the mode of administration may influence these cardioprotective effects. The present study was designed to compare the effect of interrupted administration of sevoflurane before cardiopulmonary bypass with continuous sevoflurane administration and with propofol-only anaesthesia, on cardioprotection as assessed by left ventricular performance and myocardial cell damage during coronary artery bypass grafting. Forty-two patients scheduled for coronary bypass surgery were randomly assigned to one of three groups: propofol-only (P; n = 14), continuous (SevoC; n = 14) and interrupted sevoflurane administration (SevoI; n = 14). Myocardial cell damage as assessed by Troponin T (cTNT) and creatine kinase MB (CK-MB) were chosen as the primary endpoints and echocardiographic myocardial performance index (MPI) measurements were also performed. Up to 48 h postoperatively, in group SevoI, postoperative cTNT values (mean (SD) 0.13 (0.04) ng.ml-1) were significantly (p < 0.05) lower than both the P (0.26 (0.31) ng.ml-1) and SevoC (0.25 (0.17) ng.ml-1) groups. CK-MB levels were also significantly (p < 0.05) lower in the SevoI group at 24 h after surgery and MPI significantly improved compared with both the P and SevoC groups. There was, however, no difference with respect to cytokine release and length of stay in either the intensive care unit or in the hospital. We conclude that prior interrupted sevoflurane administration confers some cardioprotection as compared with continuous sevoflurane administration or propofol-based anaesthesia.

(C) 2008 Association of Anaesthetists of Great Britain & Ireland