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.
domingo, 9 de novembro de 2008
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.
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.
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.
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.
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.
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
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
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
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
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
sexta-feira, 14 de setembro de 2007
Revisão foramen Oval -achado cirurgico
Title The Incidental Finding of a Patent Foramen Ovale During Cardiac Surgery: Should It Always Be Repaired? A Core Review.[Review]
Source Anesthesia & Analgesia. 105(3):602-610, September 2007.
Abstract With the increased use of intraoperative transesophageal echocardiography, patent foramen ovale (PFO) has become a common finding during heart surgery. This finding presents a difficult dilemma for cardiac surgeons, since the impact of intraoperatively diagnosed PFOs on postoperative outcome is unknown. Changes in the surgical plan required for closure of a PFO subject the patient to the possibility of additional risk. On the other hand, a decision to not close a PFO exposes the patient to unclear immediate and long-term consequences. Deciding whether or not to close a PFO currently depends on the clinicians' personal preferences, the probability of intraoperative and postoperative hypoxemia, and any anticipated deviation from the initial surgical plan. Most clinicians agree that an intraoperatively diagnosed PFO must be closed when surgery leads to a high risk of hypoxemia (e.g., left ventricular assist devices placement, heart transplantation); should be closed in most cases when minimal deviation from the initial surgical plan is needed for PFO closure (e.g., mitral valve or tricuspid valve surgeries); and probably, should be closed during heart surgeries performed without atriotomy and bicaval cannulation when the risk of perioperative or remote PFO-related complications is increased. The recent development of percutaneous methods of PFO closure provides a valuable backup for those cases when PFO is not closed and postoperative hypoxemia or other complications may be attributable to the uncorrected PFO.
(C) 2007 by International Anesthesia Research Society.
Source Anesthesia & Analgesia. 105(3):602-610, September 2007.
Abstract With the increased use of intraoperative transesophageal echocardiography, patent foramen ovale (PFO) has become a common finding during heart surgery. This finding presents a difficult dilemma for cardiac surgeons, since the impact of intraoperatively diagnosed PFOs on postoperative outcome is unknown. Changes in the surgical plan required for closure of a PFO subject the patient to the possibility of additional risk. On the other hand, a decision to not close a PFO exposes the patient to unclear immediate and long-term consequences. Deciding whether or not to close a PFO currently depends on the clinicians' personal preferences, the probability of intraoperative and postoperative hypoxemia, and any anticipated deviation from the initial surgical plan. Most clinicians agree that an intraoperatively diagnosed PFO must be closed when surgery leads to a high risk of hypoxemia (e.g., left ventricular assist devices placement, heart transplantation); should be closed in most cases when minimal deviation from the initial surgical plan is needed for PFO closure (e.g., mitral valve or tricuspid valve surgeries); and probably, should be closed during heart surgeries performed without atriotomy and bicaval cannulation when the risk of perioperative or remote PFO-related complications is increased. The recent development of percutaneous methods of PFO closure provides a valuable backup for those cases when PFO is not closed and postoperative hypoxemia or other complications may be attributable to the uncorrected PFO.
(C) 2007 by International Anesthesia Research Society.
Revisão heparina e trombocitopenia
Title Reducing Thrombotic Complications in the Perioperative Setting: An Update on Heparin-Induced Thrombocytopenia.[Review]
Source Anesthesia & Analgesia. 105(3):570-582, September 2007.
Abstract Heparins are widely used in the perioperative setting. Immune heparin-induced thrombocytopenia (HIT) is a serious, antibody-mediated complication of heparin therapy that occurs in approximately 0.5%-5% of patients treated with heparin for at least 5 days. An extremely prothrombotic disorder, HIT confers significant risks of thrombosis and devastating consequences on affected patients: approximately 38%-76% develop thrombosis, approximately 10% with thrombosis require limb amputation, and approximately 20%-30% die within a month. HIT antibodies are transient and typically disappear within 3 mo. In patients with lingering antibodies, however, re-exposure to heparin can be catastrophic. In the perioperative setting, heightened awareness is important for the prompt recognition, diagnosis, and treatment of HIT. HIT should be considered if the platelet count decreases 50% and/or thrombosis occurs 5-14 days after starting heparin, with other diagnoses excluded. On strong clinical suspicion of HIT, heparin should be discontinued and a parenteral alternative anticoagulant initiated, even before laboratory confirmation of HIT is obtained. Subsequent laboratory test results may help with the decision to continue with nonheparin therapy or switch back to heparin. Heparin avoidance in patients with current or previous HIT is feasible in most clinical situations, except perhaps in cardiovascular surgery. If the surgery cannot be delayed until HIT antibodies have disappeared, intraoperative alternative anticoagulation is recommended.
(C) 2007 by International Anesthesia Research Society.
Source Anesthesia & Analgesia. 105(3):570-582, September 2007.
Abstract Heparins are widely used in the perioperative setting. Immune heparin-induced thrombocytopenia (HIT) is a serious, antibody-mediated complication of heparin therapy that occurs in approximately 0.5%-5% of patients treated with heparin for at least 5 days. An extremely prothrombotic disorder, HIT confers significant risks of thrombosis and devastating consequences on affected patients: approximately 38%-76% develop thrombosis, approximately 10% with thrombosis require limb amputation, and approximately 20%-30% die within a month. HIT antibodies are transient and typically disappear within 3 mo. In patients with lingering antibodies, however, re-exposure to heparin can be catastrophic. In the perioperative setting, heightened awareness is important for the prompt recognition, diagnosis, and treatment of HIT. HIT should be considered if the platelet count decreases 50% and/or thrombosis occurs 5-14 days after starting heparin, with other diagnoses excluded. On strong clinical suspicion of HIT, heparin should be discontinued and a parenteral alternative anticoagulant initiated, even before laboratory confirmation of HIT is obtained. Subsequent laboratory test results may help with the decision to continue with nonheparin therapy or switch back to heparin. Heparin avoidance in patients with current or previous HIT is feasible in most clinical situations, except perhaps in cardiovascular surgery. If the surgery cannot be delayed until HIT antibodies have disappeared, intraoperative alternative anticoagulation is recommended.
(C) 2007 by International Anesthesia Research Society.
sábado, 25 de agosto de 2007
Sedação em POI cardiopatia congenita em UTI
Title Remifentanil-midazolam sedation for paediatric patients receiving mechanical ventilation after cardiac surgery+.[Miscellaneous Article]
Source BJA: British Journal of Anaesthesia. 99(2):252-261, August 2007.
Abstract Background: Sedation of critically ill children requiring artificial ventilation remains a therapeutic challenge due to large individual variation in drug effects and a paucity of knowledge of pharmacokinetics in this population. This study aimed to determine the pharmacokinetics of remifentanil in children requiring ventilation after cardiac surgery.
Methods: Twenty-six ventilated children aged 1 month to 9.25 yr (median 1.77 yr) who had undergone cardiac surgery were sedated with a fixed rate infusion of midazolam 50 [micro]g kg-1 h-1 and a remifentanil infusion that was commenced at 0.8 [micro]g kg-1 min-1 for a minimum of 60 min and subsequently decreased by 0.1 [micro]g kg-1 min-1every 20 min until the patient awoke. Arterial blood concentrations of remifentanil and midazolam were measured using high-performance liquid chromatography. Mixed-effects population models were fitted to the remifentanil concentration-time data.
Results: Satisfactory sedation was achieved in all patients as assessed by Comfort score during the initial maintenance and reduction phase of the remifentanil infusion. One patient was withdrawn from the study due to hypotension. Remifentanil pharmacokinetics were best described using a two-compartment allometric model. For a typical child with a body weight of 10.5 kg, clearance was 68.3 ml kg-1 min-1, intercompartmental clearance was 80 ml kg-1 min-1, the central compartment volume was 91.7 ml kg-1, and the peripheral compartment volume was 141 ml kg-1.
Conclusions: A combination of remifentanil and midazolam provided satisfactory sedation for these patients. Owing to enhanced clearance rates, smaller (younger) children will require higher remifentanil infusion rates than larger (older) children and adults to achieve equivalent blood concentrations.
Source BJA: British Journal of Anaesthesia. 99(2):252-261, August 2007.
Abstract Background: Sedation of critically ill children requiring artificial ventilation remains a therapeutic challenge due to large individual variation in drug effects and a paucity of knowledge of pharmacokinetics in this population. This study aimed to determine the pharmacokinetics of remifentanil in children requiring ventilation after cardiac surgery.
Methods: Twenty-six ventilated children aged 1 month to 9.25 yr (median 1.77 yr) who had undergone cardiac surgery were sedated with a fixed rate infusion of midazolam 50 [micro]g kg-1 h-1 and a remifentanil infusion that was commenced at 0.8 [micro]g kg-1 min-1 for a minimum of 60 min and subsequently decreased by 0.1 [micro]g kg-1 min-1every 20 min until the patient awoke. Arterial blood concentrations of remifentanil and midazolam were measured using high-performance liquid chromatography. Mixed-effects population models were fitted to the remifentanil concentration-time data.
Results: Satisfactory sedation was achieved in all patients as assessed by Comfort score during the initial maintenance and reduction phase of the remifentanil infusion. One patient was withdrawn from the study due to hypotension. Remifentanil pharmacokinetics were best described using a two-compartment allometric model. For a typical child with a body weight of 10.5 kg, clearance was 68.3 ml kg-1 min-1, intercompartmental clearance was 80 ml kg-1 min-1, the central compartment volume was 91.7 ml kg-1, and the peripheral compartment volume was 141 ml kg-1.
Conclusions: A combination of remifentanil and midazolam provided satisfactory sedation for these patients. Owing to enhanced clearance rates, smaller (younger) children will require higher remifentanil infusion rates than larger (older) children and adults to achieve equivalent blood concentrations.
Revisão de Bolqueio cervical p/ endarterectomia carotidea
Title Superficial or deep cervical plexus block for carotid endarterectomy: a systematic review of complications+.[Review]
Source BJA: British Journal of Anaesthesia. 99(2):159-169, August 2007.
Abstract Carotid endarterectomy is commonly conducted under regional (deep, superficial, intermediate, or combined) cervical plexus block, but it is not known if complication rates differ. We conducted a systematic review of published papers to assess the complication rate associated with superficial (or intermediate) and deep (or combined deep plus superficial/intermediate). The null hypothesis was that complication rates were equal. Complications of interest were: (1) serious complications related to the placement of block, (2) incidence of conversion to general anaesthesia, and (3) serious systemic complications of the surgical-anaesthetic process. We retrieved 69 papers describing a total of 7558 deep/combined blocks and 2533 superficial/intermediate blocks. Deep/combined block was associated with a higher serious complication rate related to the injecting needle when compared with the superficial/intermediate block (odds ratio 2.13, P=0.006). The conversion rate to general anaesthesia was also higher with deep/combined block (odds ratio 5.15, P < 0.0001), but there was an equivalent incidence of other systemic serious complications (odds ratio 1.13, P=0.273; NS). We conclude that superficial/intermediate block is safer than any method that employs a deep injection. The higher rate of conversion to general anaesthesia with the deep/combined block may have been influenced by the higher incidence of direct complications, but may also suggest that the superficial/combined block provides better analgesia during surgery.
Source BJA: British Journal of Anaesthesia. 99(2):159-169, August 2007.
Abstract Carotid endarterectomy is commonly conducted under regional (deep, superficial, intermediate, or combined) cervical plexus block, but it is not known if complication rates differ. We conducted a systematic review of published papers to assess the complication rate associated with superficial (or intermediate) and deep (or combined deep plus superficial/intermediate). The null hypothesis was that complication rates were equal. Complications of interest were: (1) serious complications related to the placement of block, (2) incidence of conversion to general anaesthesia, and (3) serious systemic complications of the surgical-anaesthetic process. We retrieved 69 papers describing a total of 7558 deep/combined blocks and 2533 superficial/intermediate blocks. Deep/combined block was associated with a higher serious complication rate related to the injecting needle when compared with the superficial/intermediate block (odds ratio 2.13, P=0.006). The conversion rate to general anaesthesia was also higher with deep/combined block (odds ratio 5.15, P < 0.0001), but there was an equivalent incidence of other systemic serious complications (odds ratio 1.13, P=0.273; NS). We conclude that superficial/intermediate block is safer than any method that employs a deep injection. The higher rate of conversion to general anaesthesia with the deep/combined block may have been influenced by the higher incidence of direct complications, but may also suggest that the superficial/combined block provides better analgesia during surgery.
ETE e embolia- Revisão
Title Transesophageal Echocardiography and Cardiovascular Sources of Embolism: Implications for Perioperative Management.[Review]
Source Anesthesiology. 107(2):333-346, August 2007.
Abstract Transesophageal echocardiography has become an invaluable investigation in patients with cardioembolic events because of its high sensitivity and specificity for defining detailed structure and function of the cardiovascular system. Patients who receive anesthesia and critical care may be at risk of systemic embolism from various cardiovascular sources. The main factors associated with embolism include intracardiac lesions such as thrombi, vegetations, and tumors; cardiac anomalies; and vascular disease, e.g., aortic atheroma. In this review article, the authors describe how transesophageal echocardiography may be used to identify various cardiovascular sources of embolism, provide risk stratification, influence medical therapy, and refine clinical decision making in patients receiving critical care and anesthesia. With these improvements, it is hoped that better patient outcomes may be achieved in the perioperative period.
Source Anesthesiology. 107(2):333-346, August 2007.
Abstract Transesophageal echocardiography has become an invaluable investigation in patients with cardioembolic events because of its high sensitivity and specificity for defining detailed structure and function of the cardiovascular system. Patients who receive anesthesia and critical care may be at risk of systemic embolism from various cardiovascular sources. The main factors associated with embolism include intracardiac lesions such as thrombi, vegetations, and tumors; cardiac anomalies; and vascular disease, e.g., aortic atheroma. In this review article, the authors describe how transesophageal echocardiography may be used to identify various cardiovascular sources of embolism, provide risk stratification, influence medical therapy, and refine clinical decision making in patients receiving critical care and anesthesia. With these improvements, it is hoped that better patient outcomes may be achieved in the perioperative period.
Procalcitonina x infecção
Title Assessment of the Accuracy of Procalcitonin to Diagnose Postoperative Infection after Cardiac Surgery.[Article]
Source Anesthesiology. 107(2):232-238, August 2007.
Abstract Background: Cardiopulmonary bypass induces a nonspecific inflammatory response. Procalcitonin has been advocated as a specific biomarker for infection. The authors studied the accuracy of procalcitonin to diagnose postoperative infection after cardiac surgery and compared it with those of C-reactive protein, white blood cell count, and interleukins 6 and 8.
Methods: The authors prospectively included 100 patients scheduled to undergo elective cardiac procedures with cardiopulmonary bypass. Blood samples were taken before surgery and each day over the 7-day postoperative period, and measurement of procalcitonin, C-reactive protein, white blood cell count, and interleukins 6 and 8 were performed. Diagnosis of infection was performed by a blinded expert panel. Data are expressed as value [95% confidence interval].
Results: Infection was diagnosed in 16 patients. Procalcitonin was significantly higher in infected patients, with a peak reached on the third postoperative day. Only the areas under the receiver operating curve of procalcitonin (0.88 [0.71-0.95]) and C-reactive protein (0.72 [0.58-0.82]) were significantly different from the no-discrimination curve, and that of procalcitonin was significantly different from those of C-reactive protein, white blood cell count, and interleukins 6 and 8. A procalcitonin value greater than 1.5 ng/ml beyond the second day diagnosed postoperative infection with a sensitivity of 0.93 [0.70-0.99] and a specificity of 0.80 [0.70-0.87]. Procalcitonin was significantly higher in patients who died (27.5 [1.65-40.5] vs. 1.2 [0.7-1.5] ng/ml; P < 0.001).
Conclusion: Procalcitonin is a valuable marker of bacterial infections after cardiac surgery.
Source Anesthesiology. 107(2):232-238, August 2007.
Abstract Background: Cardiopulmonary bypass induces a nonspecific inflammatory response. Procalcitonin has been advocated as a specific biomarker for infection. The authors studied the accuracy of procalcitonin to diagnose postoperative infection after cardiac surgery and compared it with those of C-reactive protein, white blood cell count, and interleukins 6 and 8.
Methods: The authors prospectively included 100 patients scheduled to undergo elective cardiac procedures with cardiopulmonary bypass. Blood samples were taken before surgery and each day over the 7-day postoperative period, and measurement of procalcitonin, C-reactive protein, white blood cell count, and interleukins 6 and 8 were performed. Diagnosis of infection was performed by a blinded expert panel. Data are expressed as value [95% confidence interval].
Results: Infection was diagnosed in 16 patients. Procalcitonin was significantly higher in infected patients, with a peak reached on the third postoperative day. Only the areas under the receiver operating curve of procalcitonin (0.88 [0.71-0.95]) and C-reactive protein (0.72 [0.58-0.82]) were significantly different from the no-discrimination curve, and that of procalcitonin was significantly different from those of C-reactive protein, white blood cell count, and interleukins 6 and 8. A procalcitonin value greater than 1.5 ng/ml beyond the second day diagnosed postoperative infection with a sensitivity of 0.93 [0.70-0.99] and a specificity of 0.80 [0.70-0.87]. Procalcitonin was significantly higher in patients who died (27.5 [1.65-40.5] vs. 1.2 [0.7-1.5] ng/ml; P < 0.001).
Conclusion: Procalcitonin is a valuable marker of bacterial infections after cardiac surgery.
DC em cirurgia cardiaca- comparação de metodos
Title An evaluation of cardiac output by five arterial pulse contour techniques during cardiac surgery.[Article]
Source Anaesthesia. 62(8):760-768, August 2007.
Abstract Summary: The bias, precision and tracking ability of five different pulse contour methods were evaluated by simultaneous comparison of cardiac output values from the conventional thermodilution technique (COtd). The five different pulse contour methods included in this study were: Wesseling's method (cZ); the Modelflow method; the LiDCO system; the PiCCO system and a recently developed Hemac method. We studied 24 cardiac surgery patients undergoing uncomplicated coronary artery bypass grafting. In each patient, the first series of COtd was used to calibrate the five pulse contour methods. In all, 199 series of measurements were accepted by all methods and included in the study. COtd ranged from 2.14 to 7.55 l.min-1, with a mean of 4.81 l.min-1. Bland-Altman analysis showed the following bias and limits of agreement: cZ, 0.23 and - 0.80 to 1.26 l.min-1; Modelflow, 0.00 and - 0.74 to 0.74 l.min-1; LiDCO, - 0.17 and - 1.55 to 1.20 l.min-1; PiCCO, 0.14 and - 1.60 to 1.89 l.min-1; and Hemac, 0.06 and - 0.81 to 0.93 l.min-1. Changes in cardiac output larger than 0.5 l.min-1 (10%) were correctly followed by the Modelflow and the Hemac method in 96% of cases. In this group of subjects, without congestive heart failure, with normal heart rhythm and reasonable peripheral circulation, the best results in absolute values as well as in tracking changes in cardiac output were measured using the Modelflow and Hemac pulse contour methods, based on non-linear three-element Windkessel models.
Source Anaesthesia. 62(8):760-768, August 2007.
Abstract Summary: The bias, precision and tracking ability of five different pulse contour methods were evaluated by simultaneous comparison of cardiac output values from the conventional thermodilution technique (COtd). The five different pulse contour methods included in this study were: Wesseling's method (cZ); the Modelflow method; the LiDCO system; the PiCCO system and a recently developed Hemac method. We studied 24 cardiac surgery patients undergoing uncomplicated coronary artery bypass grafting. In each patient, the first series of COtd was used to calibrate the five pulse contour methods. In all, 199 series of measurements were accepted by all methods and included in the study. COtd ranged from 2.14 to 7.55 l.min-1, with a mean of 4.81 l.min-1. Bland-Altman analysis showed the following bias and limits of agreement: cZ, 0.23 and - 0.80 to 1.26 l.min-1; Modelflow, 0.00 and - 0.74 to 0.74 l.min-1; LiDCO, - 0.17 and - 1.55 to 1.20 l.min-1; PiCCO, 0.14 and - 1.60 to 1.89 l.min-1; and Hemac, 0.06 and - 0.81 to 0.93 l.min-1. Changes in cardiac output larger than 0.5 l.min-1 (10%) were correctly followed by the Modelflow and the Hemac method in 96% of cases. In this group of subjects, without congestive heart failure, with normal heart rhythm and reasonable peripheral circulation, the best results in absolute values as well as in tracking changes in cardiac output were measured using the Modelflow and Hemac pulse contour methods, based on non-linear three-element Windkessel models.
PCR em anestesia em cardiopatia congenita
The Frequency of Anesthesia-Related Cardiac Arrests in Patients with Congenital Heart Disease Undergoing Cardiac Surgery.[Miscellaneous]
Source Anesthesia & Analgesia. 105(2):335-343, August 2007.
Abstract BACKGROUND: The frequency of anesthesia-related cardiac arrests during pediatric anesthesia has been reported between 1.4 and 4.6 per 10,000 anesthetics. ASA physical status >III and younger age are risk factors. Patients with congenital cardiac disease may also be at increased risk. Therefore, in this study, we evaluated the frequency of cardiac arrest in patients with congenital heart disease undergoing cardiac surgery at a large pediatric tertiary referral center.
METHODS: Using an established data registry, all cardiac arrests from January 2000 through December 2005 occurring in the cardiac operating rooms were reviewed. A cardiac arrest was defined as any event requiring external or internal chest compressions, with or without direct cardioversion. Events determined to be anesthesia-related were classified as likely related or possibly related.
RESULTS: There were 41 cardiac arrests in 40 patients (median age, 2.9 mo; range, 2 days to 23 yr) during 5213 anesthetics over the time period, for an overall frequency of 0.79%; 78% were open procedures requiring cardiopulmonary bypass and 22% closed procedures not requiring cardiopulmonary bypass. Eleven cardiac arrests (26.8%) were classified as either likely (n = 6) or possibly related (n = 5) to anesthesia, (21.1 per 10,000 anesthetics) but with no mortality; 30 were categorized as procedure-related. The incidence of anesthesia-related and procedure-related cardiac arrests was highest in neonates (P < 0.001). There was no association with year of event or experience of the anesthesiologist.
CONCLUSION: The frequency of anesthesia-related cardiac arrest in patients undergoing cardiac surgery is increased, but is not associated with an increase in mortality. Neonates and infants are at higher risk. Careful preparation and anticipation is important to ensure timely and effective resuscitation.
Source Anesthesia & Analgesia. 105(2):335-343, August 2007.
Abstract BACKGROUND: The frequency of anesthesia-related cardiac arrests during pediatric anesthesia has been reported between 1.4 and 4.6 per 10,000 anesthetics. ASA physical status >III and younger age are risk factors. Patients with congenital cardiac disease may also be at increased risk. Therefore, in this study, we evaluated the frequency of cardiac arrest in patients with congenital heart disease undergoing cardiac surgery at a large pediatric tertiary referral center.
METHODS: Using an established data registry, all cardiac arrests from January 2000 through December 2005 occurring in the cardiac operating rooms were reviewed. A cardiac arrest was defined as any event requiring external or internal chest compressions, with or without direct cardioversion. Events determined to be anesthesia-related were classified as likely related or possibly related.
RESULTS: There were 41 cardiac arrests in 40 patients (median age, 2.9 mo; range, 2 days to 23 yr) during 5213 anesthetics over the time period, for an overall frequency of 0.79%; 78% were open procedures requiring cardiopulmonary bypass and 22% closed procedures not requiring cardiopulmonary bypass. Eleven cardiac arrests (26.8%) were classified as either likely (n = 6) or possibly related (n = 5) to anesthesia, (21.1 per 10,000 anesthetics) but with no mortality; 30 were categorized as procedure-related. The incidence of anesthesia-related and procedure-related cardiac arrests was highest in neonates (P < 0.001). There was no association with year of event or experience of the anesthesiologist.
CONCLUSION: The frequency of anesthesia-related cardiac arrest in patients undergoing cardiac surgery is increased, but is not associated with an increase in mortality. Neonates and infants are at higher risk. Careful preparation and anticipation is important to ensure timely and effective resuscitation.
terça-feira, 24 de julho de 2007
Staunching Hemorrhage
Staunching Hemorrhage
New England Journal of Medicine reviewers present information about aprotinin, tranexamic acid, EACA, desmopressin, and rFVIIa. New England Journal of Medicine reviewers present information about aprotinin, tranexamic acid, EACA, desmopressin, and rFVIIa.
C_REMARK -->
Uncontrollable bleeding is every physician’s and patient’s nightmare. Such bleeding can be due to disease, injury, surgery, or anticoagulant therapy and can arise from lesions in the brain, lung, liver, or gastrointestinal or genitourinary tract. Most clinicians’ initial responses are to transfuse blood, plasma, and platelets, but adjunctive pharmacologic therapy also is available. The efficacy and safety of some of these pharmaceutical agents were reviewed by two experts in blood coagulation. The agents considered were aprotinin, tranexamic acid, -aminocaproic acid (EACA), desmopressin, and recombinant factor VIIa (rFVIIa).
Aprotinin is a powerful protease inhibitor that is derived from bovine lung tissue; it limits clot dissolution or fibrinolysis and markedly diminishes blood loss and need for transfusion in patients undergoing coronary-artery bypass surgery. However, this activity comes at a price: In one study, aprotinin, compared with placebo, doubled the risk for severe renal failure and led to higher risk for myocardial infarction, heart failure, and stroke (N Engl J Med 2006; 354:353). Other studies have confirmed these results, so aprotinin is recommended mainly for patients who are undergoing complicated procedures with very high bleeding risk.
Tranexamic acid and EACA bind to lysine receptors on plasminogen, which inhibits its conversion to plasmin (the enzyme that lyses fibrin). Although both agents have exhibited clinical efficacy, tranexamic acid is more potent than EACA, and both are weaker than aprotinin. Nevertheless, they do appear to limit blood loss and the need for reoperation. Unfortunately, the safety of these drugs has not been established firmly; a large randomized trial of tranexamic acid in cardiac surgical patients is underway.
Desmopressin induces the release of large multimers of von Willebrand factor from storage organelles in endothelial cells; these multimers enhance platelet adhesion and aggregation. Although desmopressin is quite effective in most patients with von Willebrand disease and in some with mild hemophilia A, trials of desmopressin in cardiac surgery have shown only small decreases in perioperative blood loss. Adverse effects include hyponatremia due to water retention as well as occasional thrombotic events.
Recombinant FVIIa is a potent hemostatic agent that binds to activated platelets at the site of injury and enhances thrombin generation and clot formation. This agent curbs blood loss in a variety of clinical situations, ranging from radical prostatectomy to battlefield injuries. However, not all trials have produced positive results, and no randomized controlled clinical trials have been completed. Furthermore, the optimal dose of rFVIIa is unknown; doses from 20 µg/kg to 200 µg/kg have been used. Whether observed serious thrombotic events are dose-related has not been established. Guidelines for the use of rFVIIa, including indications for treatment and identification of patients in whom treatment should be avoided because of high risk for thrombosis, are needed urgently.
— David Green, MD, PhD
Published in Journal Watch Oncology and Hematology May 30, 2007
Citation(s):
Mannucci PM and Levi M. Prevention and treatment of major blood loss. N Engl J Med 2007 May 31; 356:2301-11.
Original article (Subscription may be required)
Medline abstract (Free)
New England Journal of Medicine reviewers present information about aprotinin, tranexamic acid, EACA, desmopressin, and rFVIIa. New England Journal of Medicine reviewers present information about aprotinin, tranexamic acid, EACA, desmopressin, and rFVIIa.
C_REMARK -->
Uncontrollable bleeding is every physician’s and patient’s nightmare. Such bleeding can be due to disease, injury, surgery, or anticoagulant therapy and can arise from lesions in the brain, lung, liver, or gastrointestinal or genitourinary tract. Most clinicians’ initial responses are to transfuse blood, plasma, and platelets, but adjunctive pharmacologic therapy also is available. The efficacy and safety of some of these pharmaceutical agents were reviewed by two experts in blood coagulation. The agents considered were aprotinin, tranexamic acid, -aminocaproic acid (EACA), desmopressin, and recombinant factor VIIa (rFVIIa).
Aprotinin is a powerful protease inhibitor that is derived from bovine lung tissue; it limits clot dissolution or fibrinolysis and markedly diminishes blood loss and need for transfusion in patients undergoing coronary-artery bypass surgery. However, this activity comes at a price: In one study, aprotinin, compared with placebo, doubled the risk for severe renal failure and led to higher risk for myocardial infarction, heart failure, and stroke (N Engl J Med 2006; 354:353). Other studies have confirmed these results, so aprotinin is recommended mainly for patients who are undergoing complicated procedures with very high bleeding risk.
Tranexamic acid and EACA bind to lysine receptors on plasminogen, which inhibits its conversion to plasmin (the enzyme that lyses fibrin). Although both agents have exhibited clinical efficacy, tranexamic acid is more potent than EACA, and both are weaker than aprotinin. Nevertheless, they do appear to limit blood loss and the need for reoperation. Unfortunately, the safety of these drugs has not been established firmly; a large randomized trial of tranexamic acid in cardiac surgical patients is underway.
Desmopressin induces the release of large multimers of von Willebrand factor from storage organelles in endothelial cells; these multimers enhance platelet adhesion and aggregation. Although desmopressin is quite effective in most patients with von Willebrand disease and in some with mild hemophilia A, trials of desmopressin in cardiac surgery have shown only small decreases in perioperative blood loss. Adverse effects include hyponatremia due to water retention as well as occasional thrombotic events.
Recombinant FVIIa is a potent hemostatic agent that binds to activated platelets at the site of injury and enhances thrombin generation and clot formation. This agent curbs blood loss in a variety of clinical situations, ranging from radical prostatectomy to battlefield injuries. However, not all trials have produced positive results, and no randomized controlled clinical trials have been completed. Furthermore, the optimal dose of rFVIIa is unknown; doses from 20 µg/kg to 200 µg/kg have been used. Whether observed serious thrombotic events are dose-related has not been established. Guidelines for the use of rFVIIa, including indications for treatment and identification of patients in whom treatment should be avoided because of high risk for thrombosis, are needed urgently.
— David Green, MD, PhD
Published in Journal Watch Oncology and Hematology May 30, 2007
Citation(s):
Mannucci PM and Levi M. Prevention and treatment of major blood loss. N Engl J Med 2007 May 31; 356:2301-11.
Original article (Subscription may be required)
Medline abstract (Free)
domingo, 15 de julho de 2007
Tromboelastograma
Qualitative Thrombelastographic Detection of Tissue Factor in Human Plasma.[Miscellaneous Article]
Source Anesthesia & Analgesia. 104(1):59-64, January 2007.
Abstract BACKGROUND: Tissue factor (TF) is the principal in vivo initiator of coagulation, with normal circulating TF concentrations reported to be approximately 23-158 pg/mL. However, patients with atherosclerosis or cancer have been reported to have TF concentrations ranging between 800 and 9000 pg/mL. Of interest, thrombelastographic (TEG(R))-based measures of clot initiation and propagation have demonstrated hypercoagulability in such patients at risk for thromboembolic events. Thus, our goal in the present investigation was to establish a concentration-response relationship of the effect of TF on TEG(R) variables, and determine specificity of TF-mediated events with a monoclonal TF antibody.
METHODS: Thrombelastography was performed on normal human plasma exposed to 0, 500, 1000, or 2000 pg/mL TF. Additional experiments with plasma exposed to 0 or 750 pg/mL TF in the presence or absence of a monoclonal TF antibody (1:360 dilution, 10 min incubation) were also performed. Clot initiation time (R) and the speed of clot propagation (MRTG, maximum rate of thrombus generation) were determined.
RESULTS: The addition of TF to normal plasma resulted in a significant, concentration-dependent decrease in R and increase MRTG values. The addition of TF antibody to samples with TF significantly increased R and decreased MRTG values compared to samples with TF addition.
CONCLUSIONS: In conclusion, changes in TEG(R) variables in conjunction with use of a TF antibody can detect pathological concentrations of TF in human plasma in vitro. Further investigation is warranted to determine if TEG(R)-based monitoring could assist in the detection and prevention of TF-initiated thromboembolic events.
Source Anesthesia & Analgesia. 104(1):59-64, January 2007.
Abstract BACKGROUND: Tissue factor (TF) is the principal in vivo initiator of coagulation, with normal circulating TF concentrations reported to be approximately 23-158 pg/mL. However, patients with atherosclerosis or cancer have been reported to have TF concentrations ranging between 800 and 9000 pg/mL. Of interest, thrombelastographic (TEG(R))-based measures of clot initiation and propagation have demonstrated hypercoagulability in such patients at risk for thromboembolic events. Thus, our goal in the present investigation was to establish a concentration-response relationship of the effect of TF on TEG(R) variables, and determine specificity of TF-mediated events with a monoclonal TF antibody.
METHODS: Thrombelastography was performed on normal human plasma exposed to 0, 500, 1000, or 2000 pg/mL TF. Additional experiments with plasma exposed to 0 or 750 pg/mL TF in the presence or absence of a monoclonal TF antibody (1:360 dilution, 10 min incubation) were also performed. Clot initiation time (R) and the speed of clot propagation (MRTG, maximum rate of thrombus generation) were determined.
RESULTS: The addition of TF to normal plasma resulted in a significant, concentration-dependent decrease in R and increase MRTG values. The addition of TF antibody to samples with TF significantly increased R and decreased MRTG values compared to samples with TF addition.
CONCLUSIONS: In conclusion, changes in TEG(R) variables in conjunction with use of a TF antibody can detect pathological concentrations of TF in human plasma in vitro. Further investigation is warranted to determine if TEG(R)-based monitoring could assist in the detection and prevention of TF-initiated thromboembolic events.
Assinar:
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