Edith R. Schmid

Preconditioning by Sevoflurane Decreases Biochemical Markers for Myocardial and Renal Dysfunction in Coronary Artery Bypass Graft Surgery: A Double-blinded, Placebo-controlled, Multicenter Study

Background Preconditioning by volatile anesthetics is a promising therapeutic strategy to render myocardial tissue resistant to perioperative ischemia. It was hypothesized that sevoflurane preconditioning would decrease postoperative release of brain natriuretic peptide, a biochemical marker for myocardial dysfunction. In addition, several variables associated with the protective effects of preconditioning were evaluated. Methods Seventy-two patients scheduled for coronary artery bypass graft surgery under cardioplegic arrest were randomly assigned to preconditioning during the first 10 min of complete cardiopulmonary bypass with either placebo (oxygen–air mixture only) or sevoflurane 4 vol% (2 minimum alveolar concentration). No other volatile anesthetics were administered at any time during the study. Treatment was strictly blinded to anesthesiologists, perfusionists, and surgeons. Biochemical markers of myocardial dysfunction and injury (brain natriuretic peptide, creatine kinase–MB activity, and cardiac troponin T), and renal dysfunction (cystatin C) were determined. Results of Holter electrocardiography were recorded perioperatively. Translocation of protein kinase C was assessed by immunohistochemical analysis of atrial samples. Results Sevoflurane preconditioning significantly decreased postoperative release of brain natriuretic peptide, a sensitive biochemical marker of myocardial contractile dysfunction. Pronounced protein kinase C &dgr; and &egr; translocation was observed in sevoflurane-preconditioned myocardium. In addition, postoperative plasma cystatin C concentrations increased significantly less in sevoflurane-preconditioned patients. No differences between groups were found for perioperative ST-segment changes, arrhythmias, or creatine kinase–MB and cardiac troponin T release. Conclusions Sevoflurane preconditioning preserves myocardial and renal function as assessed by biochemical markers in patients undergoing coronary artery bypass graft surgery under cardioplegic arrest. This study demonstrated for the first time translocation of protein kinase C isoforms &dgr; and &egr; in human myocardium in response to sevoflurane.

Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?

Objective:Traditional cutoff values of serum creatinine considered to define postoperative acute renal failure have been challenged recently. In a previous investigation we demonstrated that minimal changes in serum creatinine concentration were associated with a substantial decrease in survival after cardiac surgery. In this investigation, we assessed the impact of minimal absolute increases in serum creatinine in a second institution, and we analyzed whether relative changes, as in the RIFLE classification and, partially, in Acute Kidney Injury Network (AKIN) classification, confer a different prognostic potential. Design:Prospective analysis. Setting:University hospital. Patients:All consecutive patients undergoing cardiac surgery in the University Hospital of Zurich (Center USZ) over a 46-month period. Interventions:Patients were prospectively documented. We analyzed maximal changes in serum creatinine in the first 48 hrs postoperatively (&Dgr;Crea) regarding death within 30 days. Results were compared with those of the University Hospital Vienna (Center AKH). Moreover, the prognostic potential of &Dgr;Crea within 48 hrs vs. serum creatinine elements according to RIFLE and AKIN classifications was assessed. Measurements and Main Results:A total of 3,123 patients were evaluated from USZ. The majority of patients had decreased postoperative serum creatinine values (negative &Dgr;Crea) and the lowest mortality (1.8%). Minimal increases, [0, 0.5) mg·dL−1, were associated with a more than doubled mortality in both centers (5%/6%). Mortality, according to RIFLE and AKIN classifications for both populations combined, was as follows: 7,023 (3.6%), 160 (29%), 43 (19%), and 15 (33%) for RIFLE Normal, Risk, Injury, and Failure; 6,644 (2.8), 463 (16.4), 3 (66.7), and 131 (1.8) for AKIN stage 0, 1, 2, and 3. Conclusions:Measuring repeat serum creatinine concentrations within 48 hrs and determining &Dgr;Crea were the most effective discrimination method to find patients at risk for adverse postoperative outcome after cardiac surgery, better than application of this sole criterion to the RIFLE (least discriminatory) or the AKIN classification.

Anesthetic-induced improvement of the inflammatory response to one-lung ventilation.

Background:Although one-lung ventilation (OLV) has become an established procedure during thoracic surgery, sparse data exist about inflammatory alterations in the deflated, reventilated lung. The aim of this study was to prospectively investigate the effect of OLV on the pulmonary inflammatory response and to assess possible immunomodulatory effects of the anesthetics propofol and sevoflurane. Methods:Fifty-four adults undergoing thoracic surgery with OLV were randomly assigned to receive either anesthesia with intravenously applied propofol or the volatile anesthetic sevoflurane. A bronchoalveolar lavage was performed before and after OLV on the lung side undergoing surgery. Inflammatory mediators (tumor necrosis factor &agr;, interleukin 1&bgr;, interleukin 6, interleukin 8, monocyte chemoattractant protein 1) and cells were analyzed in lavage fluid as the primary endpoint. The clinical outcome determined by postoperative adverse events was assessed as the secondary endpoint. Results:The increase of inflammatory mediators on OLV was significantly less pronounced in the sevoflurane group. No difference in neutrophil recruitment was found between the groups. A positive correlation between neutrophils and mediators was demonstrated in the propofol group, whereas this correlation was missing in the sevoflurane group. The number of composite adverse events was significantly lower in the sevoflurane group. Conclusions:This prospective, randomized clinical study suggests an immunomodulatory role for the volatile anesthetic sevoflurane in patients undergoing OLV for thoracic surgery with significant reduction of inflammatory mediators and a significantly better clinical outcome (defined by postoperative adverse events) during sevoflurane anesthesia.

Hemodilution tolerance in patients with coronary artery disease who are receiving chronic beta-adrenergic blocker therapy

Hemodilution tolerance is not well defined in patients with coronary artery disease receiving beta-adrenergic blockers chronically. Ninety patients scheduled for coronary artery bypass graft (CABG) surgery were randomized to a hemodilution (n = 60) and a control group (n = 30). During midazolam-fentanyl anesthesia, hemodynamic variables, ST segment deviation, and O2 consumption were determined prior to and after 6 and 12 mL/kg isovolemic exchange of blood for 6% hydroxyethyl starch. Hemoglobin decreased from 12.6 +/- 0.2 to 9.9 +/- 0.2 g/dL (mean +/- SEM, P < 0.05). With stable filling pressures, cardiac index increased from 2.05 +/- 0.05 to 2.27 +/- 0.05 L centered dot min-1 centered dot m-2 (P < 0.05) and O2 extraction from 27.4% +/- 0.6% to 31.2% +/- 0.7% (P < 0.05), resulting in stable O2 consumption. No alterations in ST segments were observed in leads II and V5 during hemodilution. Individual increases in cardiac index and O2 extraction were not linearly related to age and left ventricular (LV) ejection fraction (P = 0.841, P = 0.799). We conclude that isovolemic hemodilution to a hemoglobin value of 9.9 +/- 0.2 g/dL is well tolerated and fully compensated in patients with coronary artery disease receiving beta-adrenergic blockers chronically. Within the investigated ranges, the compensatory mechanisms during hemodilution are largely independent of age (35-81 yr) and LV ejection fraction (26%-83%). (Anesth Analg 1996;82:687-94)

Hemodilution Tolerance in Elderly Patients Without Known Cardiac Disease

Hemodilution tolerance is not well defined in elderly patients.In 20 patients older than 65 yr and free from known cardiovascular disease, hemodynamic variables, ST segment deviation, and O2 consumption were determined prior to and after 6 and after 12 mL/kg isovolemic exchange of blood for 6% hydroxyethyl starch. The mean age of the patients was 76 +/- 2 yr (mean +/- SEM, range 66-88 yr). During hemodilution, hemoglobin decreased from 11.6 +/- 0.4 to 8.8 +/- 0.3 g/dL (P < 0.05). With stable filling pressures, cardiac index increased from 2.02 +/- 0.11 to 2.19 +/- 0.10 L centered dot min-1 centered dot m-2 (P < 0.05) while systemic vascular resistance decreased from 1796 +/- 136 to 1568 +/- 126 dynes centered dot s centered dot cm-5 (P < 0.05) and O2 extraction increased from 28.0% +/- 0.9% to 33.0% +/- 0.8% (P < 0.05) resulting in a stable O2 consumption during hemodilution. No alterations in ST segments were observed in lead II during hemodilution. In lead V5, ST segment deviation became slightly less negative during hemodilution from -0.03 +/- 0.01 to -0.02 +/- 0.01 mV (P < 0.05). The moderate decrease in hemoglobin was fully compensated by both an increase in cardiac index and in O2 extraction. Electrocardiographic signs of myocardial ischemia were not observed in this population. In conclusion, isovolemic hemodilution to a hemoglobin value of 8.8 +/- 0.3 g/dL is well tolerated in elderly patients free from known cardiac disease at the ages of 65-88 yr. (Anesth Analg 1996;82:681-6)

Normothermia versus hypothermia during cardiopulmonary bypass: a randomized, controlled trial.

To evaluate the influence of perfusion temperature on systemic effects of cardiopulmonary bypass (CPB), 30 patients undergoing elective coronary artery bypass grafting were randomly assigned to either normothermic (warm, n = 14, 36 degrees C) or hypothermic (cold, n = 16, 28 degrees C) CPB. Serial hemodynamic measurements and blood samples were obtained before, during and after the CPB procedure. During CPB, there were no differences between both groups in the need for vasopressors (norepinephrine, phenylephrine), urinary output, or fluid balance. In the early postoperative period, normothermic CPB patients had significantly lower systemic vascular resistance and higher cardiac index measurements (mean +/- standard error: systemic vascular resistance, 880 +/- 27 versus 1,060 +/- 57 dyne.s.cm-5, p = 0.025; cardiac index, 3.6 +/- 0.1 versus 2.9 +/- 0.1 L.min-1.m-2, p = 0.01) without differences in the administration of vasoactive drugs. Blood loss was significantly higher in patients after hypothermic CPB (median [range] body surface area: 370 [180-560] versus 490 [280-2,120] mL/m2, p = 0.0006), with a greater need for transfusion of erythrocytes and fresh frozen plasma. Plasma levels of tumor necrosis factor and soluble tumor necrosis factor receptors increased during and after CPB, independent of perfusion temperature. This study suggests a significant influence of CPB temperature and respective perfusion management on postoperative hemodynamics and blood loss. Normothermic CPB is not associated with additional systemic adverse effects.

Factors influencing the individual effects of blood transfusions on oxygen delivery and oxygen consumption

ObjectiveTo determine factors influencing the individual effects of blood transfusions regarding oxygen delivery and consumption. DesignChart review. SettingA university hospital cardiosurgical intensive care unit. PatientsSixty-seven patients with 170 transfusion events evaluated. InterventionsBlood transfusion. Measurements and Main ResultsMeasurements were performed before and after a blood transfusion, separated by 302 ± 13 mins (mean ± sem). The individual increase in cardiac index resulting from a blood transfusion was inversely related to cardiac index before transfusion (p < .001), oxygen delivery index before transfusion (p < .001), and oxygen consumption index before transfusion (p < .001). The individual increase in oxygen delivery index was inversely related to oxygen consumption index before transfusion (p < .001). The individual increase in oxygen consumption index was inversely related to oxygen consumption index before transfusion (p < .001). Individual changes in cardiac index, oxygen delivery index, and oxygen consumption index were not significantly related to preoperative ejection fraction (25%–87%), age (32–81 yrs), and pretransfusion hemoglobin concentration (5.0–11.8 g/dL). ConclusionIn adult patients after cardiovascular surgery, oxygen delivery- and oxygen consumption-related variables predict the individual response to blood transfusions better than do patient characteristics such as preoperative ejection fraction, age, and pretransfusion hemoglobin concentration. Including oxygen delivery and oxygen consumption, variables into the transfusion decision, thus, may enable a more individual use of allogeneic blood in specific situations. (Crit Care Med 1999; 27:2194–2200)

Early postoperative arrhythmias after cardiac operation in children

BACKGROUND Arrhythmias are a recognized complication of cardiac operations. However, little is known about the incidence, treatment, and risk factors for early postoperative arrhythmias in children after cardiac operations. METHODS Diagnosis and treatment of early postoperative arrhythmias were prospectively analyzed in an intensive care unit in 100 consecutive children with a median age of 17 months (range, 1 day to 191 months) who had undergone cardiac operation. Patients were grouped in three different categories of surgical complexity. RESULTS During a median postoperative time of 1 day (range, 0 to 15 days), 64 critical arrhythmias occurred in 48 patients. Arrhythmias consisted of sinus bradycardia in 30, atrioventricular block II to III in 7, supraventricular tachyarrhythmias in 14, and premature complexes in 13 instances. Treatment of 52 arrhythmias was successful and included pacing in 41, intravenous amiodarone in 8, body cooling in 5, overdrive pacing in 3, and electrolyte correction in 2 cases, with more than one treatment modality in 8 cases. Risk factors for arrhythmias were lower body weight (p < 0.05), longer cardiopulmonary bypass duration (p < 0.05), and a category of higher surgical complexity (p < 0.001). CONCLUSIONS Early postoperative arrhythmias occur frequently after cardiac operations in children. Sinus bradycardia, atrioventricular block II to III, and supraventricular tachyarrhythmias are the most frequent arrhythmias, which, however, can be treated effectively by means of temporary pacing, cooling, and antiarrhythmic drug therapy. Lower body weight, longer cardiopulmonary bypass duration, and a higher surgical complexity are risk factors for early postoperative arrhythmias.

Continuous thermodilution cardiac output: clinical validation against a reference technique of known accuracy

Objective: To evaluate the accuracy and precision of continuous thermodilution (CCO) by using a validated bolus thermodilution (BCO) reference technique as criterion standard. Design: Under circulatory steady state conditions, a CCO system (Vigilance, software versions 4.35 and 4.39) was validated with regard to CCO as well as iced and room temperature BCO. Setting: Intensive care unit at a university hospital. Patients: Method comparison was conducted in 56 cardiac surgical patients, 28 patients being allocated to one of the two software versions, and 14 within each group to either iced or room temperature BCO. Measurements and results: CCO readings were registered in duplicate before and after three to five bolus injections conducted with both the Vigilance and reference systems. Iced BCO showed excellent agreement between the Vigilance and reference systems, yielding SDs of bias of 0.41 and 0.37 l/min and linear correlation coefficients (r) of 0.97 and 0.96. With room temperature BCO, agreement was significantly less. CCO, irrespective of software version, showed higher SDs of bias (0.90 and 0.84 l/min) and lower r values (0.84 and 0.81) than iced BCO (p < 0.0001). CCO measurements with software version 4.39 yielded a similar SD of bias to that with room temperature BCO. Conclusion: Decreased precision of CCO as compared to iced BCO may, in clinical settings, be outweighed by the advantages of automated and continuous monitoring. Under research conditions, however, iced BCO remains the method of choice.

Noninvasive versus invasive assessment of cardiac output after cardiac surgery: clinical validation☆

The accuracy of noninvasive cardiac output (CO) measurement techniques, such as electrical bioimpedance (BIO), suprasternal continuous-wave Doppler (CWD), pulsed-wave Doppler (PWD), and transesophageal continuous-wave Doppler (TED) ultrasound has been variably judged in recent years. In addition, clinical comparisons are hampered by the fact that there is no generally accepted gold standard in CO measurement. After coronary artery bypass surgery in 25 patients, CO was simultaneously determined by invasive standard techniques (thermodilution [TD] and Fick methods) plus BIO, CWD, PWD, and TED. There was an excellent agreement found between TD and the Fick method (COF = 0.13 + 1.01.COTD; r = 0.96; n = 99). Thermodilution was thus chosen to be the reference method. Bioimpedance underestimated COTD (COBIO = 0.47 + 0.60.COTD; r = 0.78; n = 111). Allowing physiological ejection times only led to an improved agreement between BIO and TD (COBIO = 0.05 + 0.69.COTD; r = 0.82; n = 79), but BIO still significantly underestimated COTD (P less than 0.0005). Using physiologic ejection times during COCWD determination reduced the scatter of data as compared with TD; however, CWD still considerably overestimated COTD, when COCWD computation was based on the echocardiographic aortic diameter (ECHO) (COCWD ECHO = 0.79 + 1.40.COTD; r = 0.84; n = 52). With the surgical aortic diameter (SURG), the agreement improved (COCWD SURG = 0.75 + 1.16.COTD; r = 0.89; n = 44), but overestimation of COTD remained significant (P less than 0.05). Irrespective of the aortic diameter, COPWD values showed a considerable scatter of data compared with COTD (COPWD ECHO = 1.26 + 0.60.COTD; r = 0.62; n = 64 and COPWD SURG = 1.42 + 0.41.COTD; r = 0.47; n = 61). Correlation of absolute COTED values to thermodilution depended on the method used for calibration. All investigated noninvasive CO measurement techniques unreliably measured relative CO changes. Despite its invasiveness, TD remains the method of choice for accurate CO determination in adult patients following cardiac surgery.