Accuracy of Continuous Cardiac Output Measurement With the LiDCOplus System During Intra-Aortic Counterpulsation After Cardiac Surgery.

OBJECTIVE: To evaluate the effect of intra-aortic counterpulsation on precision, accuracy, and concordance of continuous pulse contour cardiac output determined using LiDCOplus (LiDCO Group, London). DESIGN: Prospective trial. SETTING: University hospital critical care unit. PARTICIPANTS: Patients with intra-aortic balloon pump support in the 1:1 mode after elective or urgent cardiac surgery. INTERVENTIONS: Lithium dilution calibrated pulse contour cardiac output was compared with pulmonary artery bolus thermodilution cardiac output during hemodynamically stable conditions in the course of standardized postoperative management. MEASUREMENTS AND MAIN RESULTS: Fifty-one paired measurements demonstrated good correlation between the 2 methods (r = 0.88, p<0.001). Mean bias was -0.14±0.81 L/min, limits of agreement 1.48 to -1.77 L/min, and percentage error 28%. Concordance between the 2 techniques regarding directional changes>±10% cardiac output was 100% (p = 0.008). Trending ability was moderate when paired cardiac output changes were assessed using linear regression, 4-quadrant table, and polar plots. When changes <±10% of the reference cardiac output were excluded, 90% of the data pairs still lay within the 30° radial limits. Optimal timing of the balloon pump was indispensable for proper determination of pulse contour cardiac output. CONCLUSIONS: Because of the LiDCOplus-specific algorithm in determining stroke volume from the arterial pulse waveform, which differs from other devices, accuracy and precision of continuous pulse contour cardiac output only are affected insignificantly by intra-aortic counterpulsation. The authors nevertheless caution that the device should be recalibrated after major hemodynamic alterations or otherwise inexplicable changes of the pulse contour cardiac output to improve trending.

The neuroprotective effect of magnesium sulphate during iatrogenically-induced ventricular fibrillation.

UNLABELLED: We studied the neuroprotective effect of magnesium sulphate (MgSO4) administered before ventricular fibrillation was induced for internal cardioverter defibrillator threshold testing, and continued during reperfusion. METHODS: With the intention of increasing serum magnesium (Mg) to >1.2 mmol/L, 15 patients received 16 mmol of MgSO4, IV, followed by 5 mmol over two hours. Fifteen patients received placebo. Serum neuron-specific enolase (NSE) was assessed, as well as pre- and postoperative neurocognitive function. RESULTS: NSE increased in all patients, reaching a peak at 24 hours. The target Mg level was maintained throughout surgery in only nine of the Mg patients, and mainly in those with low lean body mass (LBM). In these patients, increased Mg levels were related to altered NSE release (P<0.05). NSE increased when serum Mg dropped to <1.2 mmol/L, finally exceeding levels of inadequately or untreated patients. Neurocognitive function after surgery was similar between groups. CONCLUSIONS: Insufficient dosing could account for our results, as NSE release could be inhibited by Mg >1.2 mmol/L. For neuroprotection, the Mg dosage should be adjusted according to LBM and infusion be extended to >2 hours.

Efficacy and safety of hydroxyethyl starch 6% 130/0.4 in a balanced electrolyte solution (Volulyte) during cardiac surgery.

OBJECTIVE: The infusion of large amounts of saline-based solutions may contribute to the development of hyperchloremic metabolic acidosis and the use of a balanced carrier for colloid solutions might improve postoperative acid-base status. The equivalence of 2 hydroxyethyl starch (HES) solutions and the influence on chloride levels and acid-base status by selectively changing the carrier of rapidly degradable modern 6% HES 130/0.4 were studied in cardiac surgery patients. DESIGN: A prospective, randomized, double-blinded study. SETTING: A clinical study in 2 cardiac surgery institutions. PARTICIPANTS: Eighty-one patients. INTERVENTION: Patients received either 6% HES130/0.4 balanced (Volulyte; Fresenius Kabi, Bad Homburg, Germany) or 6% HES130/0.4 saline (Voluven; Fresenius Kabi, Bad Homburg, Germany) for intra- and postoperative hemodynamic stabilization. MEASUREMENTS AND MAIN RESULTS: The therapeutic equivalence of both HES formulations regarding volume effect and superiority of the balanced electrolyte solution regarding serum chloride levels and acid-base status were measured. Similar volumes of both HES 130/0.4 balanced and HES 130/0.4 saline were administered until 6 hours after surgery, 2,391 ± 518 mL in the HES 130/0.4 balanced group versus 2,241 ± 512 mL in the HES 130/0.4 saline group. The 95% confidence interval for the difference between treatments (-77; 377 mL; mean, 150 mL) was contained entirely in the predefined interval (-500, 500 mL), thereby proving equivalence. The serum chloride level (mmol/L) was lower (p < 0.05 at the end of surgery), and arterial pH was higher in the balanced group at all time points except baseline, and base excess was less negative at all time points after baseline (p < 0.01). CONCLUSIONS: Volumes of HES needed for hemodynamic stabilization were equivalent between treatment groups. Significantly lower serum chloride levels in the HES balanced group reflected the lower chloride load of similar infusion volumes. The HES balanced group had significantly less acidosis.

Impaired recovery of cardiac output and mean arterial pressure after successful defibrillation in patients with low left ventricular ejection fraction.

BACKGROUND: Early defibrillation clearly improves survival from malignant arrhythmia. However, in some cases the cause of death will only be altered from arrhythmic to nonarrhythmic. We evaluated the impact of left ventricular ejection fraction (LVEF) on trend and recovery profile of beat-to-beat cardiac output (CO) and mean arterial blood pressure (MAP) after successful defibrillation. METHODS: We investigated 63 NYHA class I-III patients undergoing threshold testing in the course of insertion of an implantable cardioverter defibrillator (ICD) in monitored anaesthesia care. Preoperatively, LVEF was classified as either normal (>50%), moderately (30-50%) or severely impaired (<30%). CO and MAP were measured continuously throughout the implantation procedure. RESULTS: Arrest time and body mass index were not different between groups. CO in patients with severely and moderately reduced LVEF dropped 21% and 13% below baseline (P<0.05), respectively. MAP also decreased by 26% and 17%, respectively. In contrast, 45% of patients with LVEF>50% showed sympathetic activation that resulted in a 12% and 2% increase in mean values for CO and MAP, respectively. In relation to patients with LVEF<50%, CO and MAP values were significantly higher after defibrillation (P<0.05). Additionally, recovery of CO was prolonged in the groups with ventricular dysfunction (P<0.05). Temporary post-shock pacing was observed in 40% of patients. CONCLUSIONS: A large number of ICD patients with restricted LVEF appears to lack the ability to quickly restore CO and MAP after successful defibrillation. Organ reperfusion may thus still be compromised.

Cerebral desaturation during cardiac arrest: its relation to arrest duration and left ventricular pump function.

OBJECTIVE: To determine the impact of brief periods of cardiac arrest (CA) on regional cerebral oxygen saturation (rSO2) in patients with low left ventricular ejection fraction (LVEF <30%). DESIGN: Prospective observational study. SETTING: Cardiac surgery room at a university hospital. PATIENTS: Seventy-seven consecutive patients undergoing elective implantation of a cardioverter/defibrillator in monitored anesthesia care. According to preoperative assessments, left ventricular function was classified as normal (LVEF >50%), moderately impaired (LVEF 30%-50%), or severely reduced (LVEF <30%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: rSO2 was determined during threshold testing with concomitant induction of CA. In patients with LVEF <30%, mean baseline rSO2 (59%) was already below the lower range of normal despite normal arterial blood pressure, heart rate, and arterial oxygen saturation. rSO2 increased by 6% after 6 L/min oxygen insufflation (p < 0.05) and dropped again in each group after CA, reaching a nadir after successful defibrillation. Patients with LVEF <30% and baseline rSO2 <63% exhibited the lowest values. They also showed the highest incidence (11%) of critical cerebral desaturations (i.e., >20% drop from baseline or rSO2 value <50%). rSO2 in patients with LVEF <30% was always below that determined in patients with LVEF >30% (p < 0.05). There was a strong correlation between rSO2 values before CA and rSO2 nadir (p < 0.05). The drop in rSO2 was only moderately related to the brief CAs (p < 0.05). CONCLUSION: These findings demonstrate that severely compromised left ventricular pump function is associated with diminished rSO2. As these patients seem to be more susceptible to critical desaturations, they may be prone to severe tissue hypoxemia unless adequate oxygen delivery is reestablished rapidly. This may contribute to the poor neurologic outcome after successful resuscitation in patients with LVEF <30%.

The impact of perioperative atelectasis on antibiotic penetration into lung tissue: an in vivo microdialysis study.

OBJECTIVE: Postoperative pneumonia is a potentially devastating complication associated with high mortality in intensive care unit (ICU)-patients. One of the major predisposing factors is the perioperative occurrence of atelectatic formations in non-dependent lung areas. Perioperative ventilation/perfusion mismatch due to atelectasis may influence antibiotic distribution to lung tissue, hence increasing the risk of postoperative pneumonia. We evaluated whether differences in ventilation/perfusion mismatch can influence antibiotic distribution into lung tissue by means of in vivo microdialysis, comparing patients undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB) (atelectasis model), with patients operated with the off-pump coronary artery bypass grafting (OPCAB)-technique. PATIENTS AND METHODS: We compared five patients operated with CPB (CPB-group) and five patients undergoing CABG with OPCAB-technique (OPCAB-group). Levofloxacin (500 mg) was administered intravenously, after surgery, in the ICU. Time versus concentration profiles of levofloxacin in lung tissue and plasma were measured at regular time-intervals. RESULTS: In the OPCAB-group, the median of the maximum concentration of levofloxacin in lung tissue (4.1 microg ml(-1) +/- 7, range 3.7-11.8 microg ml(-1)) was significantly higher compared with the CPB-group (2.5 microg ml(-1) +/- 0.3, range 2.0-2.9 microg ml(-1)) (P = 0.046). Median levofloxacin tissue/plasma area under the concentration curve (AUC) ratio in lung tissue was 0.3 +/- 0.2 (range 0.1-0.7) in the CPB-group versus 0.7 +/- 1.6 (range 0.4-0.8) in the OPCAB-group (P = 0.015). CONCLUSIONS: Data indicate that postoperative interstitial antibiotic concentration is influenced by perioperative atelectasis formation. Our findings suggest the re-evaluation of clinical dosing schemas of antibiotic therapy in a variety of diseases associated with atelectasis formation.

In vivo microdialysis to measure antibiotic penetration into soft tissue during cardiac surgery.

BACKGROUND: Wound infections remain an important problem after cardiac surgery despite antimicrobial prophylaxis, causing increased mortality, morbidity, and costs. Penetration properties of antibiotics are altered by extracorporeal circulation, fluid resuscitation, surgery, and postoperative treatment measures. So far, interstitial antibiotic concentration has not been measured continuously during surgery. It remains uncertain whether the concentration of the prophylactic antibiotic is sufficient in interstitial tissue. Therefore, we measured interstitial concentrations of cefazolin in vivo during cardiac surgery. METHODS: Seven patients undergoing aortic valve replacement were studied in this prospective, observational, pharmacokinetic study. Cefazolin, 4 g, was administered before skin incision and additionally 2 g during skin closure. Microdialysis, an in vivo approach, was used to measure unbound interstitial drug concentrations. RESULTS: Cefazolin plasma concentration rose to a peak of 443 microg/mL (range, 169 to 802 microg/mL) within 20 minutes (range, 20 to 40 minutes). The maximum of interstitial concentration of cefazolin was observed within 60 minutes after antibiotic administration. Cefazolin tissue levels exceeded minimum inhibitory concentration values for most potential wound pathogens for more than 600 minutes after infusion. The maximum drug concentration of cefazolin in subcutaneous interstitial fluid was 22.6% of maximum plasma levels, comparable with 19.4% in muscular tissue. CONCLUSIONS: Cefazolin, administered in the high dose used at our institution, is effective for prevention against infection with the most prevalent pathogens during and immediately after cardiac surgery. Additionally, our data show that it is important to reevaluate clinical dosing schemas by means of direct in vivo measurements.

Impaired target site penetration of vancomycin in diabetic patients following cardiac surgery.

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.

In vivo measurement of levofloxacin penetration into lung tissue after cardiac surgery.

Nosocomial pneumonia is a severe complication after cardiac surgery (CS). Levofloxacin, a fluoroquinolone, qualifies for the therapy of postoperative pneumonia. However, penetration properties of levofloxacin into the lung tissue could be substantially affected by CS: atelectasis, low cardiac output after CS, high volume loads, and inflammatory capillary leak potentially influence drug distribution. The aim of our study was to gain information on interstitial antibiotic concentrations in lung tissue in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass. Therefore, six patients undergoing elective CS participated in this prospective study. A dose of 500 mg of levofloxacin was administered intravenously in addition to standard antibiotic prophylaxis immediately after the end of surgery. Time versus concentration profiles of levofloxacin in the interstitial lung tissue and plasma were determined. A microdialysis technique was used for lung interstitial concentration measurements. The microdialysis procedure was well tolerated in all patients and no adverse events were observed. The median area under the concentration curve (AUC) of levofloxacin in interstitial lung fluid was 18.6 microg.h/ml (range, 10.1 to 33.6). The median AUC for tissue (AUC(tissue)) of unbound levofloxacin/AUC(total) in plasma was 0.6 (range, 0.4 to 0.9). The median unbound AUC(tissue)/MIC was 2.4 (range, 1.3 to 4.2) for Pseudomonas aeruginosa. Our study demonstrated the feasibility and safety of microdialysis in human lung tissue in vivo after CS. The unbound AUC/MIC ratio revealed that levofloxacin used in the described manner was borderline sufficient for the treatment of nosocomial pneumonia caused by Klebsiella pneumoniae and insufficient for the treatment of pneumonia caused by Pseudomonas aeruginosa, because the breakpoint of 30 to 40 for AUC/MIC could not be reached by the conventionally used dosage schema in our post-CS setting. Penetration was lower than in previous reports.

A systematic review of currently available pharmacological neuroprotective agents as a sole intervention before anticipated or induced cardiac arrest.

We conducted a Medline search for controlled studies evaluating currently available drugs for pharmacological neuroprotection. They had to be administered prior to transient global cerebral ischaemia without further non-pharmacological measures. We deliberately excluded focal ischaemia since its pathophysiology is substantially different from global ischaemia. A total of 45 articles conducted exclusively in laboratory animals met these criteria. The following classes of agents were evaluated: anaesthetics, GABAergic drugs, calcium-antagonists, anticonvulsives, sodium-channel blockers, potassium-channel activators, NMDA-receptor antagonists, hormones, vasodilators, dopamine- and alpha2-agonists, magnesium, xanthine oxidase- and cyclooxygenase inhibitors, a nootropic, a protease inhibitor, and immunosuppressants. Some of them were applied chronically and others administered via clinically impracticable routes. The available literature favours isoflurane, phenytoin, lamotrigine, magnesium, and potentially, nimodipine, and flunarizine. If factors like costs, toxicity, side effects, route and mode of application are considered, isoflurane and MgSO4 that have also been safely applied to patients with compromised left ventricular pump function are advantageous but their true role in human neuroprotection remains unclear.

Target site penetration of fosfomycin in critically ill patients.

OBJECTIVE: The present study was undertaken to investigate the target site penetration properties of fosfomycin, an antibiotic particularly suitable for treatment of soft tissue infections (STIs) in critically ill patients. METHODS AND RESULTS: The study population included nine patients with sepsis. Penetration of fosfomycin into the interstitial space fluid of skeletal muscle was measured using the microdialysis technique, following a single intravenous administration of 8.0 g of fosfomycin to patients. The median (range) fosfomycin area under the concentration versus time profile for plasma and skeletal muscle were 673 (459-1108) and 477 (226-860) mg x h/L (P < 0.011), respectively. Interstitial maximum concentrations were lower than plasma values (P < 0.029). Median fosfomycin concentrations in the interstitium and plasma exceeded 70 mg/L throughout the observation period of 4 h and covered MICs for Streptococcus pyogenes, Staphylococcus aureus and Pseudomonas aeruginosa. Simulation of bacterial growth inhibition of S. pyogenes, based on tissue concentration data, confirmed the bactericidal properties of fosfomycin described in previous studies. CONCLUSION: Fosfomycin concentrations in muscle interstitium and plasma exceeded the MICs for a range of clinically relevant pathogens in critically ill patients. Thus, fosfomycin exhibits a tissue pharmacokinetic profile, which appears to offer an alternative to other broad-spectrum antibiotics in intensive care patients suffering from STI.