Keso Skhirtladze

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.

Comparison of the effects of albumin 5%, hydroxyethyl starch 130/0.4 6%, and Ringer's lactate on blood loss and coagulation after cardiac surgery

BACKGROUND Infusion of 5% human albumin (HA) and 6% hydroxyethyl starch 130/0.4 (HES) during cardiac surgery expand circulating volume to a greater extent than crystalloids and would be suitable for a restrictive fluid therapy regimen. However, HA and HES may affect blood coagulation and could contribute to increased transfusion requirements. METHODS We randomly assigned 240 patients undergoing elective cardiac surgery to receive up to 50 ml kg(-1) day(-1) of either HA, HES, or Ringers lactate (RL) as the main infusion fluid perioperatively. Study solutions were supplied in identical bottles dressed in opaque covers. The primary outcome was chest tube drainage over 24 h. Blood transfusions, thromboelastometry variables, perioperative fluid balance, renal function, mortality, intensive care unit, and hospital stay were also assessed. RESULTS The median cumulative blood loss was not different between the groups (HA: 835, HES: 700, and RL: 670 ml). However, 35% of RL patients required blood products, compared with 62% (HA) and 64% (HES group; P=0.0003). Significantly, more study solution had to be administered in the RL group compared with the colloid groups. Total perioperative fluid balance was least positive in the HA group [6.2 (2.5) litre] compared with the HES [7.4 (3.0) litre] and RL [8.3 (2.8) litre] groups (P<0.0001). Both colloids affected clot formation and clot strength and caused slight increases in serum creatinine. CONCLUSIONS Despite equal blood loss from chest drains, both colloids interfered with blood coagulation and produced greater haemodilution, which was associated with more transfusion of blood products compared with crystalloid use only.

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.

In Vivo Measurement of Levofloxacin Penetration into Lung Tissue after Cardiac Surgery

ABSTRACT 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 μg · h/ml (range, 10.1 to 33.6). The median AUC for tissue (AUCtissue) of unbound levofloxacin/AUCtotal in plasma was 0.6 (range, 0.4 to 0.9). The median unbound AUCtissue/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.

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%.

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.

Effect of Cardiopulmonary Bypass on Regional Antibiotic Penetration into Lung Tissue

ABSTRACT The use of cardiopulmonary bypass (CPB) during cardiac surgery causes regional ventilation-perfusion mismatch, contributing to regional disturbances in antibiotic penetration into lung tissue. Ventilation-perfusion mismatch is associated with postoperative pneumonia, a frequent and devastating complication after cardiac surgery. In this prospective clinical animal study, we performed in vivo microdialysis to determine the effect of CPB on regional penetration of levofloxacin (LVX) into lung tissue. Six pigs underwent surgery with CPB (CPB group), and another six pigs underwent surgery without CPB (off-pump coronary artery bypass grafting; OPCAB group). LVX (750 mg) was administered intravenously to all pigs immediately after surgery. For regional measurements of LVX in pulmonary concentrations, microdialysis probes were inserted in both lungs of each pig. Pigs were placed in the right lateral position. Time versus concentration profiles of unbound LVX were measured in the upper and lower lung tissue and plasma in all pigs. In all pigs, maximum concentrations (Cmax) of LVX were significantly lower in the upper lung than in the lower lung (OPCAB, P = 0.035; CPB, P < 0.001). Median Cmax of LVX showed a significant difference in the upper versus lower lung in the CPB group (P < 0.05). No significant difference was found in the median Cmax of LVX in the upper and the lower lung in the OPCAB group (P = 0.32). Our data indicate that CPB affects perioperative regional antibiotic penetration into lung tissue. Common clinical antibiotic dosing schemes should be reevaluated in patients undergoing coronary artery bypass grafting with CPB.

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.

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.