Edda M. Tschernko

On the origin of respiratory artifacts in BOLD-EPI of the human brain

BOLD-based functional MRI (fMRI) can be used to explicitly measure hemodynamic aspects and functions of human neuro-physiology. As fMRI measures changes in regional cerebral blood flow and volume as well as blood oxygenation, rather than neuronal brain activity directly, other processes that may change the above parameters have to be examined closely to assess sensitivity and specificity of fMRI results. Physiological processes that can cause artifacts include cardiac action, breathing and vasomotion. Although there has been substantial research on physiological artifacts and appropriate compensation methods, controversy still remains on the mechanisms that cause the fMRI signal fluctuations. Respiratory-correlated fluctuations may either be induced by changes of the magnetic field homogeneity due to moving organs, intra-thoracic pressure differences, respiration-dependent vasodilation or oxygenation differences. The aim of this study was to characterize the impact of different breathing patterns by varying respiration frequency and/or tidal volume on EPI time courses of the resting human brain. The amount of respiration-related oscillations during three respiration patterns was quantified, and statistically significant differences were obtained in white matter only: p < 0.03 between 6 vs. 12 ml/kg body weight end tidal volume at a respiration frequency of 15/min, p < 0.03 between 12 vs. 6 ml/kg body weight and 15 vs. 10 respiration cycles/min. There was no significant difference between 15 vs. 10 respiration cycles/min at an end tidal volume of 6 ml/kg body weight (p = 0.917). In addition, the respiration-affected brain regions were very similar with EPI readout in the a-p and l-r direction. Based on our results and published literature we hypothesize that venous oxygenation oscillations due to changing intra-thoracic pressure represent a major factor for respiration-related signal fluctuations and increase significantly with increasing end tidal volume in white matter only.

Impaired Target Site Penetration of Vancomycin in Diabetic Patients following Cardiac Surgery

ABSTRACT Soft tissue infections constitute a serious complication following surgery in diabetic patients and frequently require the administration of vancomycin. However, despite antibiotic treatment, mortality of patients with postoperative infections remains high and might be related to an impaired penetration of anti-infective agents to target tissues. Therefore, the present study was designed to measure vancomycin tissue concentrations in six diabetic and six nondiabetic patients after cardiac surgery. Vancomycin was administered as a continuous intravenous infusion at an infusion rate of 80 to 120 mg/h. Vancomycin concentrations in soft tissues and plasma were measured in all patients during steady state as “therapeutic window” concentrations in plasma by microdialysis on day 8 ± 4 after initiation of vancomycin treatment. Vancomycin tissue concentrations in diabetic patients were significantly lower than in nondiabetics (3.7 mg/liter versus 11.9 mg/liter; P = 0.002). The median vancomycintissue/vancomycinplasma concentration ratio was 0.1 in diabetic patients and 0.3 in nondiabetics (P = 0.002). Our study demonstrated that vancomycin penetration into target tissues is substantially impaired in diabetic patients versus nondiabetics. Insufficient tissue concentrations could therefore possibly contribute to failure of antibiotic treatment and the development of antimicrobial resistance in diabetic patients.

Morphologic Grading of the Emphysematous Lung and Its Relation to Improvement After Lung Volume Reduction Surgery

BACKGROUND The morphologic criteria for lung volume reduction surgery, such as severity and heterogeneity of disease, differ widely between patients, and this makes any comparison of functional results between centers difficult. Here we present a morphologic scoring system and describe its possible relation to functional results after lung volume reduction operations. METHODS Between September 1994 and December 1996, 47 consecutive patients underwent bilateral lung volume reduction operations. The morphology of emphysema was quantified with standard chest roentgenograms and computed tomographic imaging, which were used to define the following four variables: degree of hyperinflation (grade 0 to 4), degree of impairment in diaphragmatic mechanics, degree of heterogeneity (grade 0 to 4), and severity of parenchymal destruction (range, 0 to 48). RESULTS All four variables showed good reproducibility. Degree of heterogeneity had a significant influence on functional improvement in terms of forced expiratory volume in 1 second (p = 0.0413, r2 = 0.11). Severity of parenchymal destruction was significantly associated with 30-day mortality: patients who died after operation (n = 4) had a severity of parenchymal destruction of 28.4 +/- 2.1 compared with 21.3 +/- 1.0 for those who survived (n = 43) (p = 0.003). CONCLUSIONS This morphologic scoring system is easy to use, is reproducible, and allows quantification of the morphology of emphysema, thereby allowing definition of different patient subgroups. Such an exact morphologic quantification may help in the comparison of functional results between centers. Furthermore, the risk factors for certain morphologic subgroups, such as patients with a homogeneous distribution pattern, may be clarified in the future.

The Effects of Thoracic Epidural Analgesia with Bupivacaine 0.25% on Ventilatory Mechanics in Patients with Severe Chronic Obstructive Pulmonary Disease

Optimal analgesia is important after thoracotomy in pulmonary-limited patients to avoid pain-related pulmonary complications. Thoracic epidural anesthesia (TEA) can provide excellent pain relief. However, potential paralysis of respiratory muscles and changes in bronchial tone might be unfavorable in patients with end-stage chronic obstructive pulmonary disease (COPD). Therefore, we evaluated the effect of TEA on maximal inspiratory pressure, pattern of breathing, ventilatory mechanics, and gas exchange in 12 end-stage COPD patients. Pulmonary resistance, work of breathing, dynamic intrinsic positive end-expiratory pressure, and peak inspiratory and expiratory flow rates were evaluated by assessing esophageal pressure and airflow. An increase in minute ventilation (7.50 ± 2.60 vs 8.70 ± 2.10 L/min;P = 0.04) by means of increased tidal volume (0.46 ± 0.16 vs 0.53 ± 0.14 L/breath;P = 0.003) was detected after TEA. These changes were accompanied by an increase in peak inspiratory flow rate (0.48 ± 0.17 vs 0.55 ± 0.14 L/s;P = 0.02) and a decrease in pulmonary resistance (20.7 ± 9.9 vs 16.6 ± 8.1 cm H2O · L−1 · s−1;P = 0.02). Peak expiratory flow rate, dynamic intrinsic positive end-expiratory pressure, work of breathing, Pao2, and maximal inspiratory pressure were unchanged (all P > 0.50). We conclude that TEA with bupivacaine 0.25% can be used safely in end-stage COPD patients.

Functional Improvement After Volume Reduction: Sternotomy Versus Videoendoscopic Approach

BACKGROUND Volume reduction has been proved to increase ventilatory mechanics in diffuse, nonbullous lung emphysema. However, the best approach is still controversial. METHODS We retrospectively compared the perioperative data of and functional results in 15 patients having sternotomy (group I) with those of 15 patients having a videoendoscopic approach (group II). RESULTS The 30-day mortality was 2 patients in group I and 1 patient in group II. Mean duration of chest tube drainage was 8.7 +/- 1.8 days and 8.0 +/- 1.9 days and mean hospital stay, 12.3 +/- 1.9 and 12.5 +/- 2.1 days in groups I and II, respectively. Work of breathing decreased from 1.89 +/- 0.33 J/L and 1.76 +/- 0.22 J/L preoperatively to 0.75 +/- 0.06 J/L and 0.8 +/- 0.06 J/L (p < 0.01 and p < 0.05, respectively) after 3 months; and intrinsic positive end-expiratory pressure decreased from 7.15 +/- 1.31 cm H2O and 6.24 +/- 1.33 cm H2O to preoperatively 0.79 +/- 0.46 cm H2O and 1.13 +/- 0.44 cm H2O (p < 0.005 and p < 0.01, respectively) after 3 months in groups I and II, respectively. Forced expiratory volume in 1 second increased from preoperative values of 21.6% +/- 2.9% and 25.3% +/- 2.4% of predicted to 34.5% +/- 5.0% and 40.9% +/- 7.5% of predicted after 3 months (p < 0.05 in both groups) in groups I and II, respectively. CONCLUSIONS Both surgical approaches resulted in similar substantial improvement in lung function and physical fitness. The incidence of air leakage, the duration of chest tube drainage, and the hospital stay were the same for both procedures.

Renal and Ocular Hemodynamic Effects of Insulin

There is evidence that the vasodilator action of insulin is mediated by the release of nitric oxide (NO). We hypothesized that euglycemic hyperinsulinemia might increase renal and ocular blood flow, and that the vasodilator capacity of insulin might be NO-dependent. Euglycemic insulin clamps were performed in 10 healthy subjects. Sixty minutes after the start of insulin administration, an intravenous coinfusion of N-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase, or of norepinephrine (NE), an endothelium-independent vasoconstrictor, was started. Renal plasma flow was measured by para-aminohippurate (PAH) clearance method. Ocular hemodynamics were assessed by laser interferometric measurement of fundus pulsations and Doppler sonographic measurement of blood flow velocity in the ophthalmic artery. Renal plasma flow and ocular fundus pulsations were increased by insulin, L-NMMA almost completely abolished the vasodilative effects of insulin, whereas the effects of combined infusion of insulin and NE were approximately the sum of the hemodynamic changes induced by each agent alone. The results show that during euglycemic hyperinsulinemia, renal and ocular blood flow are increased, which may be mediated either by a local vasodilator effect or a systemic increase in flow. The hemodynamic effects of insulin in the kidney and the eye are at least partially dependent on NO synthesis. Because the insulin plasma levels we obtained are in the high physiological range, it may be assumed that insulin plays a role in renal and ocular blood flow regulation.

Influence of vancomycin on renal function in critically ill patients after cardiac surgery: continuous versus intermittent infusion.

Background:Vancomycin is frequently used in clinical practice to treat severe wound and systemic infections caused by Gram-positive bacteria after cardiac surgery. The drug is excreted almost entirely by glomerular filtration and might exhibit nephrotoxic side effects. This study compared the nephrotoxic impact of vancomycin during continuous versus intermittent administration. Methods:The authors analyzed 149 patients admitted to the intensive care unit during a 5-yr period. All patients were treated at the intensive care unit after elective open heart surgery. Thirty patients received a dosage of 1325 ± 603 mg/d vancomycin (range 300–3400 mg/d) by intermittent infusion, and 119 patients received a mean dosage of 1935 ± 688 mg/d (range 352–3411 mg/d) by continuous infusion. Results:Nephrotoxicity occurred in 11 patients (36.7%) in the intermittent treatment group and in 33 patients (27.7%) in the continuous treatment group (P = 0.3; 95% CI = 0.283). Continuous veno-venous hemofiltration after vancomycin administration was required for 9 patients (9 of 30; 30%) in the intermittent treatment group and for 28 (28 of 119; 23.5%) in the continuous treatment group (P = 0.053; 95% CI = 0.256). A change of one unit (1 mg/l) in vancomycin serum concentration (&Dgr;VancoC) induced an average change of 0.04 mg/dl in creatinine (&Dgr;Crea) in the intermittent treatment group versus 0.006 mg/dl in the continuous treatment group (P < 0.001). Conclusions:The data show that both the intermittent and also the continuous application modality of vancomycin are associated with deterioration of renal function in critically ill patients after cardiac surgery. However, continuous infusion showed the tendency to be less nephrotoxic than the intermittent infusion of vancomycin.

Clonidine added to bupivacaine enhances and prolongs analgesia after brachial plexus block via a local mechanism in healthy volunteers

Background and objective: The addition of clonidine to local anaesthetics enhances pain relief after peripheral nerve block, but the site of action is unproven. Methods: Seven healthy volunteers underwent three brachial block procedures using bupivacaine 0.25% 1 mg kg−1 + epinephrine 1 : 200 000 (=local analgesic) in a randomized, double-blind cross-over fashion: (a) control treatment: local analgesic with 0.9% sodium chloride solution for the block and an intramuscular injection of saline; (b) intramuscular treatment: local analgesic with 0.9% NaCl for block and an intramuscular injection of clonidine 2 μg kg−1 and (c) block treatment: local analgesic with clonidine 2 μg kg−1 for block and an intramuscular injection of saline. Results: The onset and duration of complete blockade (sensory/motor/temperature) was evaluated in the four nerve regions of the hand and forearm. Additionally, sedation score, blood pressure, heart rate and plasma clonidine concentrations were determined. The median duration of complete sensory blockade was 270 min (range 0-600) for block treatment compared to 0 min (range 0-480) for intramuscular treatment (P < 0.05) and 0 min (range 0-180) for control treatment (P < 0.05). Motor and temperature blockade exhibited similar results. Administration of clonidine was associated with sedation and a decrease in heart rate and blood pressure independent of the route of administration. Plasma clonidine concentrations were lower for block compared to the intramuscular treatment. Conclusions: The admixture of clonidine to bupivacaine plus epinephrine prolongs and enhances brachial plexus blockade. Lower clonidine plasma concentrations for block treatment strongly suggest a local effect.

Predictors of Adverse Outcome and Transient Neurological Dysfuntion Following Surgical Treatment of Acute Type A Dissections

Abstract—Predictors of adverse outcome after replacement of the ascending aorta with resection of the intimal tear and open distal anastomosis were analyzed in 167 patients (109 male, median age 56). Median hypothermic circulatory arrest (HCA) time was 30 minutes (range 12 to 113). Eighty-six patients (pts) had surgery within 24 hours and 81 within 72 hours of symptom onset. Thirty-seven pts had only ascending aortic replacement, 128 had hemiarch repair, and in 2 the entire arch was replaced. The aortic valve was replaced in 37 pts, resuspended in 116, and untouched in 14. Either death or permanent neurological dysfunction was considered an adverse outcome (AO). AO occurred in 30.5% (51/167) of patients overall. Multivariate analysis revealed that the only significant (P <0.05) independent preoperative predictor of AO was hemodynamic instability (OR 6.0). Transient neurological dysfunction (TND) occurred in 19 of 116 patients (16.4%). Significant predictors of TND were increasing age >60 (OR 3.4 and 7.0 in the second and third tertile as compared with the lowest tertile) and coronary heart disease (OR 3.4). Cumulative survival of patients (median follow-up 34 months) was 55% at 1, 49% at 5, and 44% at 8 years, indicating an excessive in-hospital mortality, but excellent long term outcome. Surgical treatment of acute type A dissections is still associated with a high incidence of adverse outcome, but results in excellent long-term survival. Earlier diagnosis, before the development of cardiac tamponade and hemodynamic compromise, is critical to improve the operative salvage rate.

Pulmonary artery thromboendarterectomy: a comparison of two different postoperative treatment strategies.

UNLABELLED Pulmonary artery thromboendarterectomy (PTE) is a potentially curative surgical procedure for chronic thromboembolic pulmonary hypertension. It is, nevertheless, associated with considerable mortality caused by postoperative complications, such as reperfusion pulmonary edema (RPE) (i.e., pulmonary infiltrates in regions distal to vessels subjected to endarterectomy) and right heart failure (RHF). However, there are no reports about the influence of different postoperative treatment strategies on complications and mortality. Therefore, we compared two different treatment strategies. In Group I (n = 33), positive inotropic catecholamines and vasodilators were avoided during termination of cardiopulmonary bypass (CPB) and thereafter, and mechanical ventilation was performed with low tidal volumes < 8 mL/kg, duration of inspiration:duration of expiration = 3:1, and peak inspiratory pressures < 18 cm H(2)O. In Group II (n = 14), positive inotropic catecholamines and vasodilators were regularly used for termination of CPB and thereafter, and ventilation was performed with high tidal volumes (10-15 mL/kg) and peak inspiratory pressures up to 50 cm H(2)O. Hemodynamics, the incidence of RPE and RHF, duration of ventilation, morbidity, and mortality were recorded. Cardiac index was comparable before surgery (2.11 +/- 0.09 vs 2.08 +/- 0.09 L. min(-1). m(-2)) and 20 min after CPB (2.26 +/- 0.09 vs 2.60 +/- 0.20 L. min(-1). m(-2)). RPE occurred in 6.1% (Group I) versus 14.3% (Group II), and RHF was observed in 9.1% (Group I) versus 21.4% (Group II). Mortality was 9.1% (Group I) versus 21.4% (Group II). Thus, the avoidance of positive inotropic catecholamines and vasodilators in combination with nonaggressive mechanical ventilation after PTE was associated with a low incidence of RPE, RHF, duration of ventilation, and mortality after PTE. IMPLICATIONS The avoidance of positive inotropic catecholamines and vasodilators in combination with nonaggressive mechanical ventilation was associated with a low incidence of reperfusion pulmonary edema and/or right heart failure after pulmonary artery thromboendarterectomy.