Protection of cerebral microcirculation, mitochondrial function, and electrocortical activity by small-volume resuscitation with terlipressin in a rat model of haemorrhagic shock.

BACKGROUND: During early treatment of haemorrhagic shock, cerebral perfusion pressure can be restored by small-volume resuscitation with vasopressors. Whether this therapy is improved with additional fluid remains unknown. We assessed the value of terlipressin and lactated Ringer's solution (LR) on early recovery of microcirculation, tissue oxygenation, and mitochondrial and electrophysiological function in the rat cerebral cortex. METHODS: Animals treated with LR replacing three times (3LR) the volume bled (n=26), terlipressin (n=27), terlipressin plus 1LR (n=26), 2LR (n=16), or 3LR (n=15) were compared with untreated (n=36) and sham-operated rats (n=17). In vivo confocal microscopy was used to assess cortical capillary perfusion, changes in tissue oxygen concentration, and mitochondrial membrane potential and redox state. Electrophysiological function was assessed by cortical somatosensory evoked potentials, spinal cord dorsum potential, and peripheral electromyography. RESULTS: Compared with sham treatment, haemorrhagic shock reduced the mean (SD) area of perfused vessels [82% (sd 10%) vs 38% (12%); P<0.001] and impaired oxygen concentration, mitochondrial redox state [99% (4%) vs 59% (15%) of baseline; P<0.001], and somatosensory evoked potentials [97% (13%) vs 27% (19%) of baseline]. Administration of terlipressin plus 1LR or 2LR was able to recover these measures, but terlipressin plus 3LR or 3LR alone were not as effective. Spinal cord dorsum potential was preserved in all groups, but no therapy protected electromyographic function. CONCLUSIONS: Resuscitation from haemorrhagic shock using terlipressin with small-volume LR was superior to high-volume LR, with regard to cerebral microcirculation, and mitochondrial and electrophysiological functions.

Trauma is associated with a better prognosis in intensive care patients with Acinetobacter infections.

PURPOSE: Acinetobacter baumannii has emerged as a common cause of infection in war-related trauma, civilian trauma and other surgical emergencies. The aim of this study was to determine prognostic factors especially trauma, in critically ill surgical patients with Acinetobacter spp. infection in a reference emergency ICU. METHODS: A retrospective review of medical records was conducted for all patients admitted to the ICU who developed Acinetobacter spp. infection from January 2007 to December 2009. Bivariate and multivariate analyses were made for 36 patients. The end-point analyzed was the in-hospital mortality. RESULTS: The initial analysis revealed a majority of young (43.6 years ± 17.1) men (92 %), trauma victims (78 %) and an in-hospital mortality of 30 %. Patients who had not suffered trauma presented with other surgical conditions and were on average older than trauma patients (57 ± 12 versus 40 ± 16 years). The overall APACHE II score average was 15.3. The ventilator-associated pneumonia was the main Acinetobacter infection diagnosed. In bivariate analysis lower Glasgow coma scale (p = 0.01) was associated with increased chance of death and being victim of trauma was a protecting factor (OR: 0.16; 95 % CI: 0.03-0.89). Receiving adequate treatment made no difference to outcome (OR: 0.55; 95 % CI: 0.05-3.15). Multivariate analysis showed that only the presence of trauma was independently associated with prognosis and was a protecting factor. CONCLUSION: Trauma was a marker of good prognosis in emergency ICU patients with Acinetobacter spp. infection.

Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery.

The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 +/- 8 years, mean weight 75.4 +/- 11.9 kg and mean body surface area 1.83 +/- 0.19 m(2)), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95% CI = 3.9-6.9) to 10.6 h (95% CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95% CI = 3.2-14.3) to 8.3 l/kg (95% CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95% CI = 7.7-24.6) vs 10.7 ml min(-1) kg(-1) (95% CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.

Computed tomography assessment of lung structure in patients undergoing cardiac surgery with cardiopulmonary bypass.

Hypoxemia is a frequent complication after coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB), usually attributed to atelectasis. Using computed tomography (CT), we investigated postoperative pulmonary alterations and their impact on blood oxygenation. Eighteen non-hypoxemic patients (15 men and 3 women) with normal cardiac function scheduled for CABG under CPB were studied. Hemodynamic measurements and blood samples were obtained before surgery, after intubation, after CPB, at admission to the intensive care unit, and 12, 24, and 48 h after surgery. Pre- and postoperative volumetric thoracic CT scans were acquired under apnea conditions after a spontaneous expiration. Data were analyzed by the paired Student t-test and one-way repeated measures analysis of variance. Mean age was 63 ± 9 years. The PaO2/FiO2 ratio was significantly reduced after anesthesia induction, reaching its nadir after CPB and partially improving 12 h after surgery. Compared to preoperative CT, there was a 31% postoperative reduction in pulmonary gas volume (P < 0.001) while tissue volume increased by 19% (P < 0.001). Non-aerated lung increased by 253 ± 97 g (P < 0.001), from 3 to 27%, after surgery and poorly aerated lung by 72 ± 68 g (P < 0.001), from 24 to 27%, while normally aerated lung was reduced by 147 ± 119 g (P < 0.001), from 72 to 46%. No correlations (Pearson) were observed between PaO2/FiO2 ratio or shunt fraction at 24 h postoperatively and postoperative lung alterations. The data show that lung structure is profoundly modified after CABG with CPB. Taken together, multiple changes occurring in the lungs contribute to postoperative hypoxemia rather than atelectasis alone.

Lung hyperinflation stimulates the release of inflammatory mediators in spontaneously breathing subjects.

Lung hyperinflation up to vital capacity is used to re-expand collapsed lung areas and to improve gas exchange during general anesthesia. However, it may induce inflammation in normal lungs. The objective of this study was to evaluate the effects of a lung hyperinflation maneuver (LHM) on plasma cytokine release in 10 healthy subjects (age: 26.1 +/- 1.2 years, BMI: 23.8 +/- 3.6 kg/m(2)). LHM was performed applying continuous positive airway pressure (CPAP) with a face mask, increased by 3-cmH(2)O steps up to 20 cmH(2)O every 5 breaths. At CPAP 20 cmH(2)O, an inspiratory pressure of 20 cmH(2)O above CPAP was applied, reaching an airway pressure of 40 cmH(2)O for 10 breaths. CPAP was then decreased stepwise. Blood samples were collected before and 2 and 12 h after LHM. TNF-alpha, IL-1beta, IL-6, IL-8, IL-10, and IL-12 were measured by flow cytometry. Lung hyperinflation significantly increased (P < 0.05) all measured cytokines (TNF-alpha: 1.2 +/- 3.8 vs 6.4 +/- 8.6 pg/mL; IL-1beta: 4.9 +/- 15.6 vs 22.4 +/- 28.4 pg/mL; IL-6: 1.4 +/- 3.3 vs 6.5 +/- 5.6 pg/mL; IL-8: 13.2 +/- 8.8 vs 33.4 +/- 26.4 pg/mL; IL-10: 3.3 +/- 3.3 vs 7.7 +/- 6.5 pg/mL, and IL-12: 3.1 +/- 7.9 vs 9 +/- 11.4 pg/mL), which returned to basal levels 12 h later. A significant correlation was found between changes in pro- (IL-6) and anti-inflammatory (IL-10) cytokines (r = 0.89, P = 0.004). LHM-induced lung stretching was associated with an early inflammatory response in healthy spontaneously breathing subjects.

Effect of cardiopulmonary bypass on the pharmacokinetics of propranolol and atenolol.

The pharmacokinetics of some beta-blockers are altered by cardiopulmonary bypass (CPB). The objective of this study was to compare the effect of coronary artery bypass graft (CABG) surgery employing CPB on the pharmacokinetics of propranolol and atenolol. We studied patients receiving oral propranolol with doses ranging from 80 to 240 mg (N = 11) or atenolol with doses ranging from 25 to 100 mg (N = 8) in the pre- and postoperative period of CABG with moderately hypothermic CPB (32 degrees C). On the day before and on the first day after surgery, blood samples were collected before beta-blocker administration and every 2 h thereafter. Plasma levels were determined using high-performance liquid chromatography and data were treated by pharmacokinetics-modelling. Statistical analysis was performed using ANOVA or the Friedman test, as appropriate, and P < 0.05 was considered to be significant. A prolongation of propranolol biological half-life from 5.41 +/- 0.75 to 11.46 +/- 1.66 h (P = 0.0028) and an increase in propranolol volume of distribution from 8.70 +/- 2.83 to 19.33 +/- 6.52 L/kg (P = 0.0032) were observed after CABG with CPB. No significant changes were observed in either atenolol biological half-life (from 11.20 +/- 1.60 to 11.44 +/- 2.89 h) or atenolol volume of distribution (from 2.90 +/- 0.36 to 3.83 +/- 0.72 L/kg). Total clearance was not changed by surgery. These CPB-induced alterations in propranolol pharmacokinetics may promote unexpected long-lasting effects in the postoperative period while the effects of atenolol were not modified by CPB surgery.

Computed tomography assessment of lung structure in patients undergoing cardiac surgery with cardiopulmonary bypass

Hypoxemia is a frequent complication after coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB), usually attributed to atelectasis. Using computed tomography (CT), we investigated postoperative pulmonary alterations and their impact on blood oxygenation. Eighteen non-hypoxemic patients (15 men and 3 women) with normal cardiac function scheduled for CABG under CPB were studied. Hemodynamic measurements and blood samples were obtained before surgery, after intubation, after CPB, at admission to the intensive care unit, and 12, 24, and 48 h after surgery. Pre- and postoperative volumetric thoracic CT scans were acquired under apnea conditions after a spontaneous expiration. Data were analyzed by the paired Student t-test and one-way repeated measures analysis of variance. Mean age was 63 ± 9 years. The PaO2/FiO2 ratio was significantly reduced after anesthesia induction, reaching its nadir after CPB and partially improving 12 h after surgery. Compared to preoperative CT, there was a 31 percent postoperative reduction in pulmonary gas volume (P < 0.001) while tissue volume increased by 19 percent (P < 0.001). Non-aerated lung increased by 253 ± 97 g (P < 0.001), from 3 to 27 percent, after surgery and poorly aerated lung by 72 ± 68 g (P < 0.001), from 24 to 27 percent, while normally aerated lung was reduced by 147 ± 119 g (P < 0.001), from 72 to 46 percent. No correlations (Pearson) were observed between PaO2/FiO2 ratio or shunt fraction at 24 h postoperatively and postoperative lung alterations. The data show that lung structure is profoundly modified after CABG with CPB. Taken together, multiple changes occurring in the lungs contribute to postoperative hypoxemia rather than atelectasis alone.

Lung hyperinflation stimulates the release of inflammatory mediators in spontaneously breathing subjects

Lung hyperinflation up to vital capacity is used to re-expand collapsed lung areas and to improve gas exchange during general anesthesia. However, it may induce inflammation in normal lungs. The objective of this study was to evaluate the effects of a lung hyperinflation maneuver (LHM) on plasma cytokine release in 10 healthy subjects (age: 26.1 ± 1.2 years, BMI: 23.8 ± 3.6 kg/m²). LHM was performed applying continuous positive airway pressure (CPAP) with a face mask, increased by 3-cmH2O steps up to 20 cmH2O every 5 breaths. At CPAP 20 cmH2O, an inspiratory pressure of 20 cmH2O above CPAP was applied, reaching an airway pressure of 40 cmH2O for 10 breaths. CPAP was then decreased stepwise. Blood samples were collected before and 2 and 12 h after LHM. TNF-á, IL-1â, IL-6, IL-8, IL-10, and IL-12 were measured by flow cytometry. Lung hyperinflation significantly increased (P < 0.05) all measured cytokines (TNF-á: 1.2 ± 3.8 vs 6.4 ± 8.6 pg/mL; IL-1â: 4.9 ± 15.6 vs 22.4 ± 28.4 pg/mL; IL-6: 1.4 ± 3.3 vs 6.5 ± 5.6 pg/mL; IL-8: 13.2 ± 8.8 vs 33.4 ± 26.4 pg/mL; IL-10: 3.3 ± 3.3 vs 7.7 ± 6.5 pg/mL, and IL-12: 3.1 ± 7.9 vs 9 ± 11.4 pg/mL), which returned to basal levels 12 h later. A significant correlation was found between changes in pro- (IL-6) and anti-inflammatory (IL-10) cytokines (r = 0.89, P = 0.004). LHM-induced lung stretching was associated with an early inflammatory response in healthy spontaneously breathing subjects.

Effect of cardiopulmonary bypass on the pharmacokinetics of propranolol and atenolol

The pharmacokinetics of some β-blockers are altered by cardiopulmonary bypass (CPB). The objective of this study was to compare the effect of coronary artery bypass graft (CABG) surgery employing CPB on the pharmacokinetics of propranolol and atenolol. We studied patients receiving oral propranolol with doses ranging from 80 to 240 mg (N = 11) or atenolol with doses ranging from 25 to 100 mg (N = 8) in the pre- and postoperative period of CABG with moderately hypothermic CPB (32°C). On the day before and on the first day after surgery, blood samples were collected before β-blocker administration and every 2 h thereafter. Plasma levels were determined using high-performance liquid chromatography and data were treated by pharmacokinetics-modelling. Statistical analysis was performed using ANOVA or the Friedman test, as appropriate, and P < 0.05 was considered to be significant. A prolongation of propranolol biological half-life from 5.41 ± 0.75 to 11.46 ± 1.66 h (P = 0.0028) and an increase in propranolol volume of distribution from 8.70 ± 2.83 to 19.33 ± 6.52 L/kg (P = 0.0032) were observed after CABG with CPB. No significant changes were observed in either atenolol biological half-life (from 11.20 ± 1.60 to 11.44 ± 2.89 h) or atenolol volume of distribution (from 2.90 ± 0.36 to 3.83 ± 0.72 L/kg). Total clearance was not changed by surgery. These CPB-induced alterations in propranolol pharmacokinetics may promote unexpected long-lasting effects in the postoperative period while the effects of atenolol were not modified by CPB surgery.

Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery

The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 ± 8 years, mean weight 75.4 ± 11.9 kg and mean body surface area 1.83 ± 0.19 m²), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95 percent CI = 3.9-6.9) to 10.6 h (95 percent CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95 percent CI = 3.2-14.3) to 8.3 l/kg (95 percent CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95 percent CI = 7.7-24.6) vs 10.7 ml min-1 kg-1 (95 percent CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.

The effects of positive end-expiratory pressure on respiratory system mechanics and hemodynamics in postoperative cardiac surgery patients

We prospectively evaluated the effects of positive end-expiratory pressure (PEEP) on the respiratory mechanical properties and hemodynamics of 10 postoperative adult cardiac patients undergoing mechanical ventilation while still anesthetized and paralyzed. The respiratory mechanics was evaluated by the inflation inspiratory occlusion method and hemodynamics by conventional methods. Each patient was randomized to a different level of PEEP (5, 10 and 15 cmH2O), while zero end-expiratory pressure (ZEEP) was established as control. PEEP of 15-min duration was applied at 20-min intervals. The frequency dependence of resistance and the viscoelastic properties and elastance of the respiratory system were evaluated together with hemodynamic and respiratory indexes. We observed a significant decrease in total airway resistance (13.12 + or - 0.79 cmH2O l-1 s-1 at ZEEP, 11.94 + or - 0.55 cmH2O l-1 s-1 (P<0.0197) at 5 cmH2O of PEEP, 11.42 + or - 0.71 cmH2O l-1 s-1 (P<0.0255) at 10 cmH2O of PEEP, and 10.32 + or - 0.57 cmH2O l-1 s-1 (P<0.0002) at 15 cmH2O of PEEP). The elastance (Ers; cmH2O/l) was not significantly modified by PEEP from zero (23.49 + or - 1.21) to 5 cmH2O (21.89 + or - 0.70). However, a significant decrease (P<0.0003) at 10 cmH2O PEEP (18.86 + or - 1.13), as well as (P<0.0001) at 15 cmH2O (18.41 + or - 0.82) was observed after PEEP application. Volume dependence of viscoelastic properties showed a slight but not significant tendency to increase with PEEP. The significant decreases in cardiac index (l min-1 m-2) due to PEEP increments (3.90 + or - 0.22 at ZEEP, 3.43 + or - 0.17 (P<0.0260) at 5 cmH2O of PEEP, 3.31 + or - 0.22 (P<0.0260) at 10 cmH2O of PEEP, and 3.10 + or - 0.22 (P<0.0113) at 15 cmH2O of PEEP) were compensated for by an increase in arterial oxygen content owing to shunt fraction reduction from 22.26 + or - 2.28 at ZEEP to 11.66 + or - 1.24 at PEEP of 15 cmH2O (P<0.0007). We conclude that increments in PEEP resulted in a reduction of both airway resistance and respiratory elastance. These results could reflect improvement in respiratory mechanics. However, due to possible hemodynamic instability, PEEP should be carefully applied to postoperative cardiac patients