Andre M. De Wolf

The Pharmacokinetics of Dexmedetomidine in Volunteers with Severe Renal Impairment

Dexmedetomidine, an &agr;2-adrenergic agonist with sedative and analgesic properties, is mainly cleared by hepatic metabolism. Because the pharmacokinetics of dexmedetomidine have not been determined in humans with impaired renal function, we studied them in volunteers with severe renal disease and in control volunteers. Six volunteers with severe renal disease and six matched volunteers with normal renal function received dexmedetomidine, 0.6 &mgr;g/kg, over 10 min. Venous blood samples for the measurement of plasma dexmedetomidine concentrations were drawn before, during, and up to 12 h after the infusion. Two-compartmental pharmacokinetic models were fit to the drug concentration versus time data. We also determined its hemodynamic, respiratory, and sedative effects. There was no difference between Renal Disease and Control groups in either volume of distribution at steady state (1.81 ± 0.55 and 1.54 ± 0.08 L/kg, respectively; mean ± sd) or elimination clearance (12.5 ± 4.6 and 8.9 ± 0.7 mL · min−1 · kg−1, respectively). However, elimination half-life was shortened in the Renal Disease group (113.4 ± 11.3 vs 136.5 ± 13.0 min;P < 0.05). A mild reduction in blood pressure occurred in most volunteers. Although most volunteers were sedated by dexmedetomidine, renal disease volunteers were sedated for a longer period of time.

Preoperative Hemoglobin Level as a Predictor of Survival After Coronary Artery Bypass Grafting A Comparison With the Matched General Population

Background— The predictive value of the preoperative hemoglobin value after coronary artery bypass grafting (CABG) has not been well established. We studied how the preoperative hemoglobin level affects the survival of patients after CABG. Late mortality was compared with that of a general population. Methods and Results— Early and late mortality of all consecutive patients undergoing isolated CABG between January 1998 and December 2007 were determined. Patients were classified into 4 groups stratified by preoperative hemoglobin level. The cutoff point for anemia was 13 g/dL for men and 12 g/dL for women. Expected survival of a matched general Dutch population cohort was obtained from the database of the Dutch Central Bureau for Statistics. After the exclusion of 122 patients who were lost to follow-up and 481 patients with missing preoperative hemoglobin levels, complete data were obtained in 10 025 patients. Multivariate logistic regression analyses revealed anemia to be an independent risk factor for higher early mortality. Cox regression analyses revealed low hemoglobin level, both as a continuous variable and as a dichotomous variable (anemia), to be a predictor of higher late mortality. Compared with expected survival, patients with the lowest preoperative hemoglobin levels had a worse outcome, whereas patients with the highest hemoglobin levels had a better outcome. Conclusions— A lower preoperative hemoglobin level is an independent predictor of late mortality in patients undergoing CABG, whereas anemia is a risk factor for early and late mortality. Compared with the general population, anemic patients had worse survival than expected, whereas nonanemic patients had better survival than expected.

Transfusion of red blood cells: The impact on short-term and long-term survival after coronary artery bypass grafting, a ten-year follow-up

Transfusion of red blood cells (RBC) and other blood products in patients undergoing coronary artery bypass grafting (CABG) is associated with increased mortality and morbidity. We retrospectively analyzed data of patients who underwent an isolated coronary bypass graft operation between January 1998 and December 2007. Mean follow-up was 1696+/-1026 days, with exclusion of 122 patients lost to follow-up and 80 patients who received 10 units of RBC. Of the remaining patients, 8001 (76.7%) received no RBC, 1621 (15.2%) received 1-2 units of RBC, 593 (5.7%) received 3-5 units and 220 (2.1%) received 6-10 units. The number of transfused RBC was a predictor for early but not for late mortality. When compared to expected survival, survival of patients not receiving any blood product was better, while survival of patients receiving >3 units of RBC was worse. Transfusion of RBC is an independent, dose-dependent risk factor for early mortality after revascularization. Compared to expected survival, receiving no RBC improves patient long-term survival, whereas receiving three or more units of RBC significantly decreases patient survival.

Effect of Body Mass Index on Early and Late Mortality After Coronary Artery Bypass Grafting

BACKGROUND The effect of obesity on the long-term outcome after coronary artery bypass graft surgery (CABG) remains controversial. We analyzed data of patients undergoing CABG in a single center, to determine the predictive value of body mass index in combination with comorbidities on early and late mortality. METHODS Early and late mortality of consecutive patients undergoing isolated CABG from January 1998 until December 2007 were determined. Patients were classified into five groups according to preoperative body mass index: underweight, normal weight, overweight, obese, and morbidly obese. RESULTS After excluding 122 patients who were lost to follow-up and 236 patients with missing preoperative body mass index, 10,268 patients were studied. Multivariate logistic regression analyses showed that underweight was associated with higher early mortality (hazard ratio 2.63; 95% confidence interval: 1.13 to 6.11, p = 0.025). Multivariate Cox regression analyses did reveal morbid obesity as an independent predictor of late mortality (hazard ratio 1.67, 95% confidence interval: 1.15 to 2.43, p = 0.007). CONCLUSIONS Among patients undergoing isolated CABG, underweight is an independent predictor for early mortality, and morbid obesity is an independent predictor for late mortality.

Uptake of desflurane and isoflurane during closed-circuit anesthesia with spontaneous and controlled mechanical ventilation

Although theoretical models predict uptake of inhaled anesthetics during closed-circuit anesthesia (CCA), clinical data for most anesthetics are conflicting or non-existent. In addition, the effects of patient characteristics and mode of ventilation on anesthetic uptake are unclear. Forty-one ASA physical status I or II adult patients undergoing a variety of 1-1.5 h surgical procedures were randomly allocated to receive CCA with desflurane or isoflurane with ventilation being either spontaneous or controlled. An end-expired anesthetic concentration of 1.3 minimum alveolar anesthetic concentration (MAC) was maintained by continuous injection of the liquid anesthetic into the circuit using a syringe pump. After an initial 4-min wash-in period, uptake during the first hour of CCA was nearly constant. Uptake was the same whether ventilation was spontaneous or controlled. Patient characteristics (age, height, weight, weight3/4, and body surface area) were comparable between groups and did not correlate with uptake. The virtually constant uptake after wash-in of desflurane and isoflurane contrasts with the square root of time model of Lowe and Ernst. These findings may greatly simplify CCA. (Anesth Analg 1997;84:413-8)

The successful use of low-dose recombinant tissue plasminogen activator for treatment of intracardiac/pulmonary thrombosis during liver transplantation

Intracardiac thrombosis and pulmonary embolism are uncommon complications during liver transplantation but carry a high mortality rate. We report the successful use of low-dose recombinant tissue plasminogen activator (0.5-4 mg) administration in 4 patients. Early diagnosis through transesophageal echocardiography and pulmonary artery catheterization may have contributed to the rapid thrombolysis.

Preoperative ejection fraction as a predictor of survival after coronary artery bypass grafting: comparison with a matched general population.

BackgroundPreoperative left ventricular dysfunction is an established risk factor for early and late mortality after revascularization. This retrospective analysis demonstrates the effects of preoperative ejection fraction on the short-term and long-term survival of patients after coronary artery bypass grafting.MethodsEarly and late mortality were determined retrospectively in 10 626 consecutive patients who underwent isolated coronary bypass between January 1998 and December 2007. The subjects were divided into 3 groups according to their preoperative ejection fraction. Expected survival was estimated by comparison with a general Dutch population group described in the database of the Dutch Central Bureau for Statistics. For each of our groups with a known preoperative ejection fraction, a general Dutch population group was matched for age, sex, and year of operation.Results and DiscussionOne hundred twenty-two patients were lost to follow-up. In 219 patients, the preoperative ejection fraction could not be retrieved. In the remaining patients (n = 10 285), the results of multivariate logistic regression and Cox regression analysis identified the ejection fraction as a predictor of early and late mortality. When we compared long-term survival and expected survival, we found a relatively poorer outcome in all subjects with an ejection fraction of < 50%. In subjects with a preoperative ejection fraction of > 50%, long-term survival exceeded expected survival.ConclusionsThe severity of left ventricular dysfunction was associated with poor survival. Compared with the survival of the matched general population, our coronary bypass patients had a worse outcome only if their preoperative ejection fraction was < 50%.

United States Practice Patterns in the Use of Transesophageal Echocardiography During Adult Liver Transplantation

OBJECTIVE To characterize contemporary practice patterns in the use of transesophageal echocardiography during adult liver transplantation and to identify factors preventing more frequent use. DESIGN Online questionnaire. SETTING Liver transplantation centers in the United States performing 12 or more adult liver transplants in 2011. PARTICIPANTS One representative from each qualifying center: The transplant anesthesiology director, a transplant anesthesiologist personally known to the authors, or the department of anesthesiology chair. INTERVENTIONS Three e-mail attempts were made to solicit participation in the study between June and August 2012. MEASUREMENTS AND MAIN RESULTS Of the 97 institutions identified, an anesthesiologist from each of 79 (81.4%) centers completed the questionnaire; 38.0% of centers reported routine use and 57.0% for special circumstances or rescue situations, yielding an overall use rate of 94.9%. This distribution was consistent regardless of operative volume, practice size, or academic affiliation. The sole factor predictive of routine transesophageal echocardiography use was an overlap between an institutions cardiac and transplant anesthesiology teams. In practices not routinely employing the technology, the most compelling reason was a sense that it was not necessary. Although 69.9% of transplant anesthesiologists reportedly were proficient in echocardiography, inadequate anesthesiologist training was also a strongly cited hindrance. CONCLUSIONS Transesophageal echocardiography during adult liver transplantation in the United States has become widely prevalent, with notable growth in its use as a routine diagnostic and monitoring modality. Almost all institutions now use the technology at least occasionally, with the participation of cardiac anesthesiologists being predictive of a centers routine use.

Pulmonary artery catheter: rest in peace? Not just quite yet...

Patients with severe liver disease have a hyperdynamic circulation with an elevated cardiac output (CO), low systemic vascular resistance, and increased heart rate. During liver transplantation (LTx), most clinicians prefer to keep CO elevated in order to maintain tissue perfusion; this practice is based on common sense and supported indirectly by a clinical study by Parker et al. CO is one of the most important parameters that the anesthesiologist follows because it is a major factor in oxygen transport. Intraoperative hemodynamic management during LTx is based on the interpretation of the CO, heart rate, pulmonary artery (PA) pressures, filling pressures, and mixed-venous oxygen saturation (SvO2) and is influenced by the stage of the procedure and other factors (for example, the use of venovenous bypass). The pulmonary artery catheter (PAC) readily provides all this hemodynamic information, and every LTx anesthesiologist is very familiar with the PAC. Modified PACs give us continuous CO or additional information about the right ventricle (ejection fraction and end-diastolic and end-systolic volumes). The right ventricular ejection fraction catheter is used infrequently despite the better preload information it provides: filling pressures do not reflect preload very well because of compliance issues. Transesophageal echocardiography (TEE) gives other important hemodynamic information that is unavailable from the PAC: TEE allows the direct visualization of the volume status, overall contractility, regional wall motion, embolization, and large vessels. However, it does not provide the kind of hemodynamic information that is available from the PAC and is not as good at trending information (especially preload). Few LTx anesthesiologists are familiar with it, and the interpretation is highly user-dependent. Finally, TEE monitoring cannot be continued easily postoperatively. For these reasons, TEE is used fairly infrequently during LTx. The few anesthesiologists who do use TEE consider the information that it provides to be complementary to that provided by the PAC; in other words, TEE does not replace the PAC at this moment and is indicated only when there is a specific condition (for example, cardiac disease and pulmonary hypertension). In this issue of Liver Transplantation, 2 teams report that CO determined by ultrasound cardiac output monitoring (USCOM) correlates very well with thermodilution CO, the gold standard. These reports on USCOM are important because they are the first to document that in these hyperdynamic patients there is also a good correlation. USCOM is a noninvasive technique (the probe is placed at the suprasternal notch) and therefore is expected to have a very low complication rate. Whether USCOM-derived information such as the corrected flow time and stroke volume variation will provide clinically valuable information regarding preload, as promised by some, remains to be seen. Also, USCOM estimations of PA pressures based on Doppler interrogation of the PA remain unvalidated (especially in those with pulmonary hypertension), and the ability to estimate left ventricular contractility is currently just a promise. Particularly worrisome is that 3 of 13 patients in one of these studies were excluded: in 2 patients, diagnostic-quality images could not be obtained, and this occurred after the patients were screened preoperatively to see whether the suprasternal insonation window was appropriate.

Risk factors for deterioration of renal function after coronary artery bypass grafting

OBJECTIVE Various definitions of impairment of renal function after coronary artery bypass grafting (CABG) are used in the literature. Depending on the definition, several risk factors are identified. We analysed our data to determine the risk factors for postoperative deterioration of the creatinine clearance of 10% or more. METHODS All patients undergoing isolated coronary surgery in a single centre between January 1998 and December 2007 are included. Clinical data, including demographics and renal risk factors, were prospectively collected in our database. The most recent preoperative serum creatinine level and the maximum serum creatinine level within the first week postoperatively were used to calculate the creatinine clearance. A deterioration of 10% or more was considered to be an endpoint for this study. RESULTS In 10098 out of a total of 10626 patients, the preoperative as well as the postoperative creatinine clearance could be calculated. In 1053 patients, the deterioration of the creatinine clearance was 10% or more. We could identify the following risk factors: advanced age, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, emergency operation, previous cardiac surgery, low preoperative haemoglobin level, high preoperative C-reactive protein level, perioperative myocardial infarction, re-exploration and the number of blood transfusions. CONCLUSIONS Risk factors for the deterioration of renal function after revascularisation have been confirmed in this study. In addition, we found peripheral vascular disease, previous cardiac surgery, low preoperative haemoglobin, increased preoperative C-reactive protein level, perioperative myocardial infarction and the number of blood transfusions to be risk factors that have not been described earlier.