Neurological and respiratory effects of lung protective ventilation in acute brain injury patients without lung injury: brain vent, a single centre randomized interventional study.

INTRODUCTION: Lung protective ventilation (LPV) comprising low tidal volume (VT) and high positive end-expiratory pressure (PEEP) may compromise cerebral perfusion in acute brain injury (ABI). In patients with ABI, we investigated whether LPV is associated with increased intracranial pressure (ICP) and/or deranged cerebral autoregulation (CA), brain compensatory reserve and oxygenation. METHODS: In a prospective, crossover study, 30 intubated ABI patients with normal ICP and no lung injury were randomly assigned to receive low VT [6 ml/kg/predicted (pbw)]/at either low (5 cmH2O) or high PEEP (12 cmH2O). Between each intervention, baseline ventilation (VT 9 ml/kg/pbw and PEEP 5 cmH2O) were resumed. The safety limit for interruption of the intervention was ICP above 22 mmHg for more than 5 min. Airway and transpulmonary pressures were continuously monitored to assess respiratory mechanics. We recorded ICP by using external ventricular drainage or a parenchymal probe. CA and brain compensatory reserve were derived from ICP waveform analysis. RESULTS: We included 27 patients (intracerebral haemorrhage, traumatic brain injury, subarachnoid haemorrhage), of whom 6 reached the safety limit, which required interruption of at least one intervention. For those without intervention interruption, the ICP change from baseline to "low VT/low PEEP" and "low VT/high PEEP" were 2.2 mmHg and 2.3 mmHg, respectively, and considered clinically non-relevant. None of the interventions affected CA or oxygenation significantly. Interrupted events were associated with high baseline ICP (p < 0.001), low brain compensatory reserve (p < 0.01) and mechanical power (p < 0.05). The transpulmonary driving pressure was 5 ± 2 cmH2O in both interventions. Partial arterial pressure of carbon dioxide was kept in the range 34-36 mmHg by adjusting the respiratory rate, hence, changes in carbon dioxide were not associated with the increase in ICP. CONCLUSIONS: The present study found that most patients did not experience any adverse effects of LPV, neither on ICP nor CA. However, in almost a quarter of patients, the ICP rose above the safety limit for interrupting the interventions. Baseline ICP, brain compensatory reserve, and mechanical power can predict a potentially deleterious effect of LPV and can be used to personalize ventilator settings. Trial registration NCT03278769 . Registered September 12, 2017.

Physiological Changes in Subjects Exposed to Accidental Hypothermia: An Update.

Background: Accidental hypothermia (AH) is an unintended decrease in body core temperature (BCT) to below 35°C. We present an update on physiological/pathophysiological changes associated with AH and rewarming from hypothermic cardiac arrest (HCA). Temperature Regulation and Metabolism: Triggered by falling skin temperature, Thyrotropin-Releasing Hormone (TRH) from hypothalamus induces release of Thyroid-Stimulating Hormone (TSH) and Prolactin from pituitary gland anterior lobe that stimulate thyroid generation of triiodothyronine and thyroxine (T4). The latter act together with noradrenaline to induce heat production by binding to adrenergic ß3-receptors in fat cells. Exposed to cold, noradrenaline prompts degradation of triglycerides from brown adipose tissue (BAT) into free fatty acids that uncouple metabolism to heat production, rather than generating adenosine triphosphate. If BAT is lacking, AH occurs more readily. Cardiac Output: Assuming a 7% drop in metabolism per °C, a BCT decrease of 10°C can reduce metabolism by 70% paralleled by a corresponding decline in CO. Consequently, it is possible to maintain adequate oxygen delivery provided correctly performed cardiopulmonary resuscitation (CPR), which might result in approximately 30% of CO generated at normal BCT. Liver and Coagulation: AH promotes coagulation disturbances following trauma and acidosis by reducing coagulation and platelet functions. Mean prothrombin and partial thromboplastin times might increase by 40-60% in moderate hypothermia. Rewarming might release tissue factor from damaged tissues, that triggers disseminated intravascular coagulation. Hypothermia might inhibit platelet aggregation and coagulation. Kidneys: Renal blood flow decreases due to vasoconstriction of afferent arterioles, electrolyte and fluid disturbances and increasing blood viscosity. Severely deranged renal function occurs particularly in the presence of rhabdomyolysis induced by severe AH combined with trauma. Conclusion: Metabolism drops 7% per °C fall in BCT, reducing CO correspondingly. Therefore, it is possible to maintain adequate oxygen delivery after 10°C drop in BCT provided correctly performed CPR. Hypothermia may facilitate rhabdomyolysis in traumatized patients. Victims suspected of HCA should be rewarmed before being pronounced dead. Rewarming avalanche victims of HCA with serum potassium > 12 mmol/L and a burial time >30 min with no air pocket, most probably be futile.

Prioritized Brain Circulation During Ergometer Cycling with Apnea and Face Immersion in Ice-Cold Water: A Case Report.

BACKGROUND: Successful cardiopulmonary resuscitation after drowning or avalanche is often attributed to hypothermia-induced decrease in metabolism, which adapts the oxygen demand to the amount supplied under cardiac compression. Four decades ago, we speculated if oxygen-sparing mechanisms like those found in marine mammals, may improve cerebral oxygenation during acute airway blockade in humans. We investigated hemodynamic changes during steady state ergometer cycling with intermittent periods of apnea and face immersion (AFI) in ice-cold water. During AFI, heart rate (HR) dropped by 58% whereas average blood velocity (ABV) determined by means of a Doppler ultrasound velocity meter (UNIDOP University of Oslo, Oslo, Norway) fell by 85% in the radial artery and rose by 67% in the vertebral artery. Similar changes occured in radial artery ABV, albeit more slowly, when the test subject only held his breath while cycling. When he breathed via a snorkel during face immersion, HR remained unchanged while radial artery ABV fell transiently and subsequently returned to its pre-immersion level. These findings later were confirmed by other investigators. Moreover, a recent study revealed that the seal even has a system for selective brain cooling during the dive. CONCLUSION: Our research has confirmed prioritized cerebral circulation during AFI in cold water. We hypothesize that these changes may improve brain oxygenation due both to greater blood flow and possibly also to faster brain cooling, as demonstrated in diving seals.

Rewarming From Hypothermic Cardiac Arrest Applying Extracorporeal Life Support: A Systematic Review and Meta-Analysis.

Introduction: This systematic review and meta-analysis aims at comparing outcomes of rewarming after accidental hypothermic cardiac arrest (HCA) with cardiopulmonary bypass (CPB) or/and extracorporeal membrane oxygenation (ECMO). Material and Methods: Literature searches were limited to references with an abstract in English, French or German. Additionally, we searched reference lists of included papers. Primary outcome was survival to hospital discharge. We assessed neurological outcome, differences in relative risks (RR) of surviving, as related to the applied rewarming technique, sex, asphyxia, and witnessed or unwitnessed HCA. We calculated hypothermia outcome prediction probability score after extracorporeal life support (HOPE) in patients in whom we found individual data. P < 0.05 considered significant. Results: Twenty-three case observation studies comprising 464 patients were included in a meta-analysis comparing outcomes of rewarming with CPB or/and ECMO. One-hundred-and-seventy-two patients (37%) survived to hospital discharge, 76 of 245 (31%) after CPB and 96 of 219 (44 %) after ECMO; 87 and 75%, respectively, had good neurological outcomes. Overall chance of surviving was 41% higher (P = 0.005) with ECMO as compared with CPB. A man and a woman had 46% (P = 0.043) and 31% (P = 0.115) higher chance, respectively, of surviving with ECMO as compared with CPB. Avalanche victims had the lowest chance of surviving, followed by drowning and people losing consciousness in cold environments. Assessed by logistic regression, asphyxia, unwitnessed HCA, male sex, high initial body temperature, low pH and high serum potassium (s-K+) levels were associated with reduced chance of surviving. In patients displaying individual data, overall mean predictive surviving probability (HOPE score; n = 134) was 33.9 ± 33.6% with no significant difference between ECMO and CPB-treated patients. We also surveyed 80 case reports with 96 victims of HCA, who underwent resuscitation with CPB or ECMO, without including them in the meta-analysis. Conclusions: The chance of surviving was significantly higher after rewarming with ECMO, as compared to CPB, and in patients with witnessed compared to unwitnessed HCA. Avalanche victims had the lowest probability of surviving. Male sex, high initial body temperature, low pH, and high s-K+ were factors associated with low surviving chances.

Thromboelastometry for Assessing Risks of Free Flap Thrombosis in Patients Undergoing Microvascular Surgery.

Introduction: Coagulation assessment is often missing in microvascular surgery. We aimed at evaluating the predictive value of thromboelastometry for free flap thrombosis in microvascular surgery patients. Materials and Methods: We enrolled 103 adult patients with traumatic injuries scheduled for microvascular free flap surgery into a prospective observational study. Thirty-six patients with recent trauma underwent surgery within 30 days (ES group), and were compared with 67 trauma patients who underwent surgery later than 30 days (late surgery, LS group) after the injury. Rotational thromboelastometry (RTE) was performed before surgery. Functional fibrinogen to platelet ratio (FPR) ≥ 42 was selected as the main hypercoagulability index. Free flap thrombosis was set as primary outcome. Thrombotic risk factors and duration of surgery related to free flap thrombosis were secondary outcomes. Statistical significance p < 0.05; not significant NS. Results: Six patients (16.7%) in the ES group and 10 (14.9%) in the LS group had free flap thrombosis (NS). In the entire cohort, free flap thrombosis rate increased in the presence of thrombogenic comorbidities (OR 4.059, CI 1.33-12.37; p = 0.014) and prolonged surgery times (OR 1.007, CI 1 - 1.012; p = 0.05). Although hypercoagulability occurred more frequently in the ES group (44.4%) than in the LS group (11.9%; p < 0.001), it was not associated with higher free flap thrombosis rate. In ES group patients with surgery times > 240 min, the risk of free flap thrombosis increased (OR 3.5, CI 1.16-10.6; p = 0.026) with 93.3% sensitivity and 86.7% specificity (AUC 0.85; p = 0.007). In contrast, in LS patients hypercoagulability increased the odds of free flap thrombosis (OR 8.83, CI 1.74-44.76; p = 0.009). Moreover, a positive correlation was found between FPR ≥ 42 and free flap thrombosis rate (r = 0.362; p = 0.003). In the LS group, the presence of thrombogenic comorbidities correlated with free flap thrombosis rate (OR 7, CI 1.591-30.8; p = 0.01). Conclusions: In LS patients with thrombogenic comorbidities, thromboelastometry supports the detection of hypercoagulability and predicts free flap thrombosis risk. In ES patients, postoperative hypercoagulability did not predict free flap thrombosis. Prolonged surgery time should be considered as a risk factor.

Fibrinolytic System Changes in Liver Surgery: A Pilot Observational Study.

Introduction: Bleeding occurs frequently in liver surgery. Unbalance between tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) concentrations might increase bleeding. Our aim was to analyze perioperative fibrinolytic changes during liver surgery. Materials and Methods: We evaluated 15 patients for inclusion into a prospective pilot study of liver surgery. We assessed fibrinolysis by plasma PAI-1 and t-PA: before surgery (T1), before Pringle maneuver (PM;T2), at the end of surgery (T3) and 24 h postoperatively (T4), and registered demographic and laboratory data, extent and duration of surgery, hemodynamic parameters, blood loss, and transfused volumes of blood products. Data presented as mean ± SD. Significance at P < 0.05. Results: After exclusion of six patients only undergoing biopsies, we included six women and three men aged 49.1 ± 19.6 years; two patients with liver metastases of colorectal cancer and hepatocellular carcinoma, respectively, two with focal nodular hyperplasia, two with hepatic hemangioma, and one with angiomyolipoma. Six patients underwent PM. PAI-1 plasma concentration (n = 9) rose from 6.25 ± 2.25 at T1 through 17.30 ± 14.59 ng/ml at T2 and 28.74 ± 20.4 (p = 0.007) and 22.5 ± 16.0 ng/ml (p = 0.04), respectively, at T3 and T4. Correspondingly, t-PA plasma concentration (n = 9) increased from 4.76 ± 3.08 ng/ml at T1 through 8.00 ± 5.10 ng/ml (p = 0.012) at T2 and decreased to 4.25 ± 2.29 ng/ml and 3.04 ± 3.09 at T3 and T4, respectively. Plasma t-PA level at T2 was significantly different from those at T1, T3, and T4 (p < 0.004). In PM patients, t-PA levels increased from T1, peaked at T2 (p = 0.001), and subsequently decreased at T3 and T4 (p = 0.011 and p = 0.037), respectively. Mean blood loss was 1,377.7 ± 1,062.8 ml; seven patients received blood products. Patients with higher PAI-1 levels at T3 received more fresh frozen plasma (r = 0.79; p = 0.01) and red blood cells (r = 0.88; p = 0.002). Conclusions: During liver surgery, fibrinolysis increased, as evidenced by rises in plasma PAI-1and t-PA, especially after start of surgery and following PM. Transfused volumes of blood products correlated with higher plasma concentrations of PAI-1. Confirming this tendency requires a larger cohort of patients.

Influence of a New "Call-Out Algorithm" for Management of Postoperative Pain and Its Side Effects on Length of Stay in Hospital: A Two-Centre Prospective Randomized Trial.

BACKGROUND: We recently introduced the efficacy safety score (ESS) as a new "call-out algorithm" for management of postoperative pain and side effects. In this study, we report the influence of ESS recorded hourly during the first 8 hours after surgery on the mobility degree, postoperative nonsurgical complications, and length of hospital stay (LOS). METHODS: We randomized 1152 surgical patients into three groups for postoperative observation: (1) ESS group (n = 409), (2) Verbal Numeric Rate Scale (VNRS) for pain group (n = 417), and (3) an ordinary qualitative observation (Control) group (n = 326). An ESS > 10 or VNRS > 4 at rest or a nurse's observation of pain or adverse reaction to analgesic treatment in the Control group served as a "call-out alarm" for an anaesthesiologist. RESULTS: We found no significant differences in the mobility degree and number of postoperative nonsurgical complications between the groups. LOS was significantly shorter with 12.7 ± 6.3 days (mean ± SD) in the ESS group versus 14.2 ± 6.2 days in the Control group (P < 0.001). CONCLUSION: Postoperative ESS recording in combination with the possibility to call upon an anaesthesiologist when exceeding the threshold score might have contributed to the reductions of LOS in this two-centre study. This trial is registered with NCT02143128.

Development and validation of the Efficacy Safety Score (ESS), a novel tool for postoperative patient management.

BACKGROUND: Several reports have shown that postoperative monitoring of general safety and quality issues, including pain treatment, after discharge from recovery is often non-systematic and inadequate. We suggest a new score with assessment of key recovery parameters, as a supportive tool for postoperative care and a call-out algorithm for need of extra help. The aim of this investigation was to validate the score. METHODS: After suggesting a prototype score from a pilot study in 182 postoperative patients, we performed a Delphi process by using international experts to create consensus on the final score contents and called the revised tool the Efficacy Safety Score (ESS). Then, we performed a prospective observational study with the ESS throughout the first 24 h postoperatively in 207 surgical in-patients. We compared ESS with Modified Early Warning Systems (MEWS), and postoperative journal information. We subsequently validated ESS by addressing recognized quality criteria for measurement of health status questionnaires. RESULTS: A call-out value of ESS ≥10 correlated with MEWS > 0 values and journal information about postoperative concerns with a sensitivity of 94% and 92%, respectively. All serious safety issues were identified with the ESS ≥ 10, and a higher number of quality issues were identified than with routine care or MEWS. We obtained positive ratings for six out of seven tested criteria of questionnaire quality; one criterion had an indeterminate rating. CONCLUSION: ESS fulfils suggested criteria for score quality validation and reflects the patient's postoperative status adequately and with high sensitivity. Further clinical trials are warranted to evaluate the usefulness of ESS as a simple tool for assessment of the postoperative safety and quality of patients.

Estimated continuous cardiac output based on pulse wave transit time in off-pump coronary artery bypass grafting: a comparison with transpulmonary thermodilution.

To evaluate the accuracy of estimated continuous cardiac output (esCCO) based on pulse wave transit time in comparison with cardiac output (CO) assessed by transpulmonary thermodilution (TPTD) in off-pump coronary artery bypass grafting (OPCAB). We calibrated the esCCO system with non-invasive (Part 1) and invasive (Part 2) blood pressure and compared with TPTD measurements. We performed parallel measurements of CO with both techniques and assessed the accuracy and precision of individual CO values and agreement of trends of changes perioperatively (Part 1) and postoperatively (Part 2). A Bland-Altman analysis revealed a bias between non-invasive esCCO and TPTD of 0.9 L/min and limits of agreement of ±2.8 L/min. Intraoperative bias was 1.2 L/min with limits of agreement of ±2.9 L/min and percentage error (PE) of 64 %. Postoperatively, bias was 0.4 L/min, limits of agreement of ±2.3 L/min and PE of 41 %. A Bland-Altman analysis of invasive esCCO and TPTD after OPCAB found bias of 0.3 L/min with limits of agreement of ±2.1 L/min and PE of 40 %. A 4-quadrant plot analysis of non-invasive esCCO versus TPTD revealed overall, intraoperative and postoperative concordance rate of 76, 65, and 89 %, respectively. The analysis of trending ability of invasive esCCO after OPCAB revealed concordance rate of 73 %. During OPCAB, esCCO demonstrated poor accuracy, precision and trending ability compared to TPTD. Postoperatively, non-invasive esCCO showed better agreement with TPTD. However, invasive calibration of esCCO did not improve the accuracy and precision and the trending ability of method.

Activation of Coagulation and Fibrinolysis in Acute Respiratory Distress Syndrome: A Prospective Pilot Study.

INTRODUCTION: Coagulation and fibrinolysis remain sparsely addressed with regards to acute respiratory distress syndrome (ARDS). We hypothesized that ARDS development might be associated with changes in plasma coagulation and fibrinolysis. Our aim was to investigate the relationships between ARDS diagnosis and plasma concentrations of tissue factor (TF), tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) in mechanically ventilated patients at increased risk of developing ARDS. MATERIALS AND METHODS: We performed an ethically approved prospective observational pilot study. Inclusion criteria were patients with PaO2/FiO2 < 300 mmHg admitted to the intensive care unit (ICU) for mechanical ventilation for 24 h, or more, because of one or more disease conditions associated with increased risk of developing ARDS. Exclusion criteria were age below 18 years; cardiac disease. We sampled plasma prospectively and compared patients who developed ARDS with those who did not using descriptive statistics and chi-square analysis of baseline demographical and clinical data. We also analyzed plasma concentrations of TF, t-PA, and PAI-1 at inclusion (T0) and on third (T3) and seventh day (T7) of the ICU stay with non-parametric statistics inclusive their sensitivity and specificity associated with the development of ARDS using receiver operating characteristic curve analysis. Statistical significance: p < 0.05. RESULTS: Of 24 patients at risk, 6 developed mild ARDS and 4 of each moderate or severe ARDS, respectively, 3 ± 2 (mean ± SD) days after inclusion. Median plasma concentrations of TF and PAI-1 were significantly higher at T7 in patients with ARDS, as compared to non-ARDS. Simultaneously, we found moderate correlations between plasma concentrations of TF and PAI-1, TF and PaO2/FiO2, and positive end-expiratory pressure and TF. TF plasma concentration was associated with ARDS with 71% sensitivity and 100% specificity, a cut off level of 145 pg/ml and AUC 0.78, p = 0.02. PAI-1 displayed 64% sensitivity and 100% specificity with a cut off concentration of 117.5 pg/ml and AUC 0.77, p = 0.02. t-PA did not change significantly during the observation time. CONCLUSION: This pilot study showed that increased plasma concentrations of TF and PAI-1 might support ARDS diagnoses in mechanically ventilated patients after 7 days in ICU.

Effects of Constant Flow vs. Constant Pressure Perfusion on Fluid Filtration in Severe Hypothermic Isolated Blood-Perfused Rat Lungs.

BACKGROUND: Victims of severe accidental hypothermia are prone to fluid extravasation but rarely develop lung edema. We hypothesize that combined hypothermia-induced increase in pulmonary vascular resistance (PVR) and a concomitant fall in cardiac output protect the lungs against edema development. Our aim was to explore in hypothermic-isolated blood-perfused rat lungs whether perfusion at constant pressure influences fluid filtration differently from perfusion at constant flow. METHODS: Isolated blood-perfused rat lungs were hanging freely in a weight transducer for measuring weight changes (ΔW). Fluid filtration coefficient (Kfc), was determined by transiently elevating left atrial pressure (Pla) by 5.8 mmHg two times each during normothermia (37°C) and during hypothermia (15°C). The lung preparations were randomized to two groups. One group was perfused with constant flow (Constant flow group) and the other group with constant pulmonary artery pressure (Constant PPA group). Microvascular pressure (Pmv) was determined before and during elevation of Pla (ΔPmv) by means of the double occlusion technique. Kfc was calculated with the formula Kfc = ΔW/ΔPmv/min. All Kfc values were normalized to predicted lung weight (PLW), which was based on body weight (BW) according to the formula: PLW = 0.0053 BW - 0.48 and presented as KfcPLW in mg/min/mmHg/g. At cessation, bronchoalveolar lavage (BAL) fluid/perfusate protein concentration (B/P) ratio was determined photometrically. Data were analyzed with parametric or non-parametric tests as appropriate. p < 0.05 considered as significant. RESULTS: Perfusate flow remained constant in the Constant flow group, but was more than halved during hypothermia in the Constant PPA group concomitant with a more fold increase in PVR. In the Constant flow group, KfcPLW and B/P ratio increased significantly by more than 10-fold during hypothermia concerted by visible signs of edema in the trachea. Hemoglobin and hematocrit increased within the Constant flow group and between the groups at cessation of the experiments. CONCLUSION: In hypothermic rat lungs perfused at constant flow, fluid filtration coefficient per gram PLW and B/P ratio increased more than 10-fold concerted by increased hemoconcentration, but the changes were less in hypothermic lungs perfused at constant PPA.

Polymorphisms on PAI-1 and ACE genes in association with fibrinolytic bleeding after on-pump cardiac surgery.

BACKGROUND: Carriers of plasminogen activator inhibitor -1 (PAI-1) -675 genotype 5G/5G may be associated with lower preoperative PAI-1 plasma levels and higher blood loss after heart surgery using cardiopulmonary bypass (CPB). We speculate if polymorphisms of PAI-1 -844 A/G and angiotensin converting enzyme (ACE) intron 16 I/D also might promote fibrinolysis and increase postoperative bleeding. METHODS: We assessed PAI-1 -844 A/G, and ACE intron 16 I/D polymorphisms by polymerase chain reaction technique and direct sequencing of genomic DNA from 83 open heart surgery patients that we have presented earlier. As primary outcome, accumulated chest tube drainage (CTD) at 4 and 24 h were analyzed for association with genetic polymorphisms. As secondary outcome, differences in plasma levels of PAI-1, t-PA/PAI-1 complex and D-dimer were determined for each polymorphism. SPSS® was used for statistical evaluation. RESULTS: The lowest preoperative PAI-1 plasma levels were associated with PAI-1 -844 genotype G/G, and higher CTD, as compared with genotype A/A at 4 and 24 h after surgery. Correspondingly, 4 h after the surgery CTD was higher in carriers of ACE intron 16 genotype I/I, as compared with genotype D/D. PAI-1 plasma levels and t-PA/PAI-1 complex reached nadir in carriers of ACE intron 16 genotype I/I, in whom we also noticed the highest D-dimer levels immediately after surgery. Notably, carriers of PAI-1 -844 genotype G/G displayed higher D-dimer levels at 24 h after surgery as compared with those of genotype A/G. CONCLUSIONS: Increased postoperative blood loss secondary to enhanced fibrinolysis was associated with carriers of PAI-1 -844 G/G and ACE Intron 16 I/I, suggesting that these genotypes might predict increased postoperative blood loss after cardiac surgery using CPB.

Monitoring of anesthetic depth during surgical correction of acquired valvular disorders: single center, randomized trial.

OBJECTIVE: The authors' primary objective was to test the hypothesis that Cerebral State Index (CSI)-guided control of anesthetic depth might reduce the consumption of anesthetics and shorten the duration of ICU and hospital stays after surgical correction of combined valve disorders. DESIGN: Single center, randomized trial. SETTING: City Hospital Number 1 of Arkhangelsk, Russian Federation. PARTICIPANTS: Fifty adult patients with combined valve disorders requiring surgical correction. INTERVENTIONS: The patients were randomized into 2 groups. In the CSI group, anesthetic depth was monitored, and the rate of infusion of propofol was titrated to maintain the depth of anesthesia corresponding to a CSI of 40-60. In the control group, the depth of anesthesia was monitored clinically, and the dosage of propofol was administered according to the recommendations of the manufacturer. MEASUREMENTS AND MAIN RESULTS: All patients received standard perioperative monitoring. Consumption of anesthetics and length of ICU and hospital stays were recorded. Preoperative patient characteristics did not differ significantly between the groups. In the CSI group, average intraoperative doses of midazolam and propofol were reduced by 41% and 19%, respectively (p<0.01). Maintenance of anesthesia guided by CSI shortened the time until fit for ICU discharge by 50% and reduced the lengths of ICU and postoperative hospital stays by 35% and 25%, respectively (p< 0.05). CONCLUSIONS: Monitoring of anesthetic depth reduces the requirements for midazolam and propofol, resulting in a faster recovery and a shorter postoperative ICU and hospital stay after surgical correction of combined valve disorders.

Normothermic cardiopulmonary bypass increases cerebral tissue oxygenation during combined valve surgery: a single-centre, randomized trial.

OBJECTIVES: In cardiac surgery, the choice of temperature regimen during cardiopulmonary bypass (CPB) remains a subject of debate. Hypothermia reduces tissue metabolic demands, but may impair the autoregulation of cerebral blood flow and contribute to neurological morbidity. The aim of this study was to evaluate the effect of two different temperature regimens during CPB on the systemic oxygen transport and the cerebral oxygenation during surgical correction of acquired heart diseases. METHODS: In a prospective study, we randomized 40 adult patients with combined valvular disorders requiring surgical correction of two or more valves into two groups: (i) a normothermic (NMTH) group (n = 20), in which the body core temperature was maintained at 36.6°C during CPB and (ii) a hypothermic (HPTH) group (n = 20), in which the body was cooled to a core temperature of 32°C maintained throughout the period of CPB. The systemic oxygen transport and the cerebral oxygen saturation (SctO2) were assessed by means of a PiCCO2 haemodynamic monitor and a cerebral oximeter, respectively. All the patients received standard perioperative monitoring. We assessed haemodynamic and oxygen transport parameters, the duration of mechanical ventilation and the length of the ICU and the hospital stays. RESULTS: During CPB, central venous oxygen saturation was significantly higher in the HPTH group but SctO2 was increased in the NMTH group (P < 0.05). Cardiac index, systemic oxygen delivery and consumption increased postoperatively in both groups. However, oxygen delivery and consumption were significantly higher in the NMTH group (P < 0.05). The duration of respiratory support and the length of ICU and hospital stays did not differ between the groups. CONCLUSIONS: During combined valve surgery, normothermic CPB provides lower central venous oxygen saturation, but increases cerebral tissue oxygenation when compared with the hypothermic regimen.

PAI-1 and t-PA/PAI-1 complex potential markers of fibrinolytic bleeding after cardiac surgery employing cardiopulmonary bypass.

BACKGROUND: Enhanced bleeding remains a serious problem after cardiac surgery, and fibrinolysis is often involved. We speculate that lower plasma concentrations of plasminogen activator inhibitor - 1 (PAI-1) preoperatively and tissue plasminogen activator/PAI-1 (t-PA/PAI-1) complex postoperatively might predispose for enhanced fibrinolysis and increased postoperative bleeding. METHODS: Totally 88 adult patients (mean age 66 ± 10 years) scheduled for cardiac surgery, were enrolled into a prospective study. Blood samples were collected pre-operatively, on admission to the recovery and at 6 and 24 hours postoperatively. Patients with a surgical bleeding that was diagnosed during reoperation were discarded from the study. The patients were allocated to two groups depending on the 24-hour postoperative chest tube drainage (CTD): Group I > 500ml, Group II ≤ 500ml. Associations between CTD, PAI-1, t-PA/PAI-1 complex and D-dimer were analyzed with SPSS. RESULTS: Nine patients were excluded because of surgical bleeding. Of the 79 remaining patients, 38 were allocated to Group I and 41 to Group II. The CTD volumes correlated with the preoperative plasma levels of PAI-1 (r = - 0.3, P = 0.009). Plasma concentrations of preoperative PAI-1 and postoperative t-PA/PAI-1 complex differed significantly between the groups (P < 0.001 and P = 0.012, respectively). Group I displayed significantly lower plasma concentrations of fibrinogen and higher levels of D-dimer from immediately after the operation and throughout the first 24 hours postoperatively. CONCLUSIONS: Lower plasma concentrations of PAI-1 preoperatively and t-PA/PAI-1 complex postoperatively leads to higher plasma levels of D-dimer in association with more postoperative bleeding after cardiac surgery.

Derecruitment test and surfactant therapy in patients with acute lung injury.

Introduction. A recruitment maneuver (RM) may improve gas exchange in acute lung injury (ALI). The aim of our study was to assess the predictive value of a derecruitment test in relation to RM and to evaluate the efficacy of RM combined with surfactant instillation in patients with ALI. Materials and Methods. Thirteen adult mechanically ventilated patients with ALI were enrolled into a prospective pilot study. The patients received protective ventilation and underwent RM followed by a derecruitment test. After a repeat RM, bovine surfactant (surfactant group, n = 6) or vehicle only (conventional therapy group, n = 7) was instilled endobronchially. We registered respiratory and hemodynamic parameters, including extravascular lung water index (EVLWI). Results. The derecruitment test decreased the oxygenation in 62% of the patients. We found no significant correlation between the responses to the RM and to the derecruitment tests. The baseline EVLWI correlated with changes in SpO(2) following the derecruitment test. The surfactant did not affect gas exchange and lung mechanics but increased EVLWI at 24 and 32 hrs. Conclusions. Our study demonstrated no predictive value of the derecruitment test regarding the effects of RM. Surfactant instillation was not superior to conventional therapy and might even promote pulmonary edema in ALI.

Increased extravascular lung water reduces the efficacy of alveolar recruitment maneuver in acute respiratory distress syndrome.

Introduction. In acute respiratory distress syndrome (ARDS) the recruitment maneuver (RM) is used to reexpand atelectatic areas of the lungs aiming to improve arterial oxygenation. The goal of our paper was to evaluate the response to RM, as assessed by measurements of extravascular lung water index (EVLWI) in ARDS patients. Materials and Methods. Seventeen adult ARDS patients were enrolled into a prospective study. Patients received protective ventilation. The RM was performed by applying a continuous positive airway pressure of 40 cm H(2)O for 40 sec. The efficacy of the RM was assessed 5 min later. Patients were identified as responders if PaO(2)/FiO(2) increased by >20% above the baseline. EVLWI was assessed by transpulmonary thermodilution before the RM, and patients were divided into groups of low EVLWI (<10 mL/kg) and high EVLWI (≥10 mL/kg). Results. EVLWI was increased in 12 patients. Following RM, PaO(2)/FiO(2) increased by 33 (4-65) % in the patients with low EVLWI, whereas those in the high EVLWI group experienced a change by only -1((-13)-(+5)) % (P = 0.035). Conclusion. In ARDS, the response to a recruitment maneuver might be related to the severity of pulmonary edema. In patients with incresed EVLWI, the recruitment maneuver is less effective.

Inhibitor of neuronal nitric oxide synthase improves gas exchange in ventilator-induced lung injury after pneumonectomy.

BACKGROUND: Mechanical ventilation with high tidal volumes may cause ventilator-induced lung injury (VILI) and enhanced generation of nitric oxide (NO). We demonstrated in sheep that pneumonectomy followed by injurious ventilation promotes pulmonary edema. We wished both to test the hypothesis that neuronal NOS (nNOS), which is distributed in airway epithelial and neuronal tissues, could be involved in the pathogenesis of VILI and we also aimed at investigating the influence of an inhibitor of nNOS on the course of VILI after pneumonectomy. METHODS: Anesthetized sheep underwent right pneumonectomy, mechanical ventilation with tidal volumes (VT) of 6 mL/kg and FiO2 0.5, and were subsequently randomized to a protectively ventilated group (PROTV; n = 8) keeping VT and FiO2 unchanged, respiratory rate (RR) 25 inflations/min and PEEP 4 cm H2O for the following 8 hrs; an injuriously ventilated group with VT of 12 mL/kg, zero end-expiratory pressure, and FiO2 and RR unchanged (INJV; n = 8) and a group, which additionally received the inhibitor of nNOS, 7-nitroindazole (NI) 1.0 mg/kg/h intravenously from 2 hours after the commencement of injurious ventilation (INJV + NI; n = 8). We assessed respiratory, hemodynamic and volumetric variables, including both the extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI). We measured plasma nitrite/nitrate (NOx) levels and examined lung biopsies for lung injury score (LIS). RESULTS: Both the injuriously ventilated groups demonstrated a 2-3-fold rise in EVLWI and PVPI, with no significant effects of NI. In the INJV group, gas exchange deteriorated in parallel with emerging respiratory acidosis, but administration of NI antagonized the derangement of oxygenation and the respiratory acidosis significantly. NOx displayed no significant changes and NI exerted no significant effect on LIS in the INJV group. CONCLUSION: Inhibition of nNOS improved gas exchange, but did not reduce lung water extravasation following injurious ventilation after pneumonectomy in sheep.

Comparison of goal-directed hemodynamic optimization using pulmonary artery catheter and transpulmonary thermodilution in combined valve repair: a randomized clinical trial.

Our aim was to compare the effects of goal-directed therapy guided either by pulmonary artery catheter (PAC) or by transpulmonary thermodilution (TTD) combined with monitoring of oxygen transport on perioperative hemodynamics and outcome after complex elective valve surgery. Measurements and Main Results. Forty patients were randomized into two equal groups: a PAC group and a TTD group. In the PAC group, therapy was guided by mean arterial pressure (MAP), cardiac index (CI) and pulmonary artery occlusion pressure (PAOP), whereas in the TTD group we additionally used global end-diastolic volume index (GEDVI), extravascular lung water index (EVLWI), and oxygen delivery index (DO(2)I). We observed a gradual increase in GEDVI, whereas EVLWI and PAOP decreased by 20-30% postoperatively (P < 0.05). The TTD group received 20% more fluid accompanied by increased stroke volume index and DO(2)I by 15-20% compared to the PAC group (P < 0.05). Duration of mechanical ventilation was increased by 5.2 hrs in the PAC group (P = 0.04). Conclusions. As compared to the PAC-guided algorithm, goal-directed therapy based on transpulmonary thermodilution and oxygen transport increases the volume of fluid therapy, improves hemodynamics and DO(2)I, and reduces the duration of respiratory support after complex valve surgery.