Changes of cortical perfusion in the early phase of subarachnoid bleeding in a rat model and the role of intracranial hypertension.

Brain perfusion is reduced early after subarachnoid hemorrhage (SAH) due to intracranial hypertension and early vasospasm. The contribution of these two mechanisms is unknown. By performing a prophylactic decompressive craniectomy (DC) in a rat model of SAH we aimed to study brain perfusion after the component of intracranial hypertension has been eliminated. We used 2x2 factorial design, where rats received either decompressive craniectomy or sham operation followed by injection of 250 microl of blood or normal saline into prechiasmatic cistern. The cortical perfusion has been continually measured by laser speckle-contrast analysis for 30 min. Injection of blood caused a sudden increase of intracranial pressure (ICP) and drop of cerebral perfusion, which returned to baseline within 6 min. DC effectively prevented the rise of ICP, but brain perfusion after SAH was significantly lower and took longer to normalize compared to non-DC animals due to increased cerebral vascular resistance, which lasted throughout 30 min experimental period. Our findings suggest that intracranial hypertension plays dominant role in the very early hypoperfusion after SAH whilst the role of early vasospasm is only minor. Prophylactic DC effectively maintained cerebral perfusion pressure, but worsened cerebral perfusion by increased vascular resistance.

Early changes of brain perfusion after subarachnoid hemorrhage - the effect of sodium nitroprusside.

Causes of early hypoperfusion after subarachnoid hemorrhage (SAH) include intracranial hypertension as well as vasoconstriction. The aim of the study was to assess the effect of intracerebroventricular (ICV) administration of sodium nitroprusside (SNP) on early hypoperfusion after SAH. Male Wistar rats (220-240 g) were used, SAH group received 250 microl of fresh autologous arterial blood into the prechiasmatic cistern; sham-operated animals received 250 microl of isotonic solution. Therapeutic intervention: ICV administration of 10 microg SNP; 5 microl 5 % glucose (SNP vehicle) and untreated control. Brain perfusion and invasive blood pressure were monitored for 30 min during and after induction of SAH. Despite SNP caused increase of perfusion in sham-operated animals, no response was observed in half of SAH animals. The other half developed hypotension accompanied by brain hypoperfusion. There was no difference between brain perfusion in SNP-treated, glucose-treated and untreated SAH animals during the monitored period. We did not observe expected beneficial effect of ICV administration of SNP after SAH. Moreover, half of the SNP-treated animals developed serious hypotension which led to brain hypoperfusion. This is the important finding showing that this is not the option for early management in patient after SAH.

Perioperative cardiovascular complications versus perioperative bleeding in consecutive patients with known cardiac disease undergoing non-cardiac surgery. Focus on antithrombotic medication. The PRAGUE-14 registry.

BACKGROUND: Interruption of antithrombotic treatment before surgery may prevent bleeding, but at the price of increasing cardiovascular complications. This prospective study analysed the impact of antithrombotic therapy interruption on outcomes in non-selected surgical patients with known cardiovascular disease (CVD). METHODS: All 1200 consecutive patients (age 74.2 ± 10.2 years) undergoing major non-cardiac surgery (37.4 % acute, 61.4 % elective) during a period of 2.5 years while having at least one CVD were enrolled. Details on medication, bleeding, cardiovascular complications and cause of death were registered. RESULTS: In-hospital mortality was 3.9 % (versus 0.9 % mortality among 17,740 patients without CVD). Cardiovascular complications occurred in 91 (7.6 %) patients (with 37.4 % case fatality). Perioperative bleeding occurred in 160 (13.3 %) patients and was fatal in 2 (1.2 % case fatality). Multivariate analysis revealed age, preoperative anaemia, history of chronic heart failure, acute surgery and general anaesthesia predictive of cardiovascular complications. For bleeding complications multivariate analysis found warfarin use in the last 3 days, history of hypertension and general anaesthesia as independent predictive factors. Aspirin interruption before surgery was not predictive for either cardiovascular or for bleeding complications. CONCLUSIONS: Perioperative cardiovascular complications in these high-risk elderly all-comer surgical patients with known cardiovascular disease are relatively rare, but once they occur, the case fatality is high. Perioperative bleeding complications are more frequent, but their case fatality is extremely low. Patterns of interruption of chronic aspirin therapy before major non-cardiac surgery are not predictive for perioperative complications (neither cardiovascular, nor bleeding). Simple baseline clinical factors are better predictors of outcomes than antithrombotic drug interruption patterns.

Anidulafungin for the treatment of candidaemia/invasive candidiasis in selected critically ill patients.

A prospective, multicentre, phase IIIb study with an exploratory, open-label design was conducted to evaluate efficacy and safety of anidulafungin for the treatment of candidaemia/invasive candidiasis (C/IC) in specific ICU patient populations. Adult ICU patients with confirmed C/IC meeting ≥ 1 of the following criteria were enrolled: post-abdominal surgery, solid tumour, renal/hepatic insufficiency, solid organ transplant, neutropaenia, and age ≥ 65 years. Patients received anidulafungin (200 mg on day 1, 100 mg/day thereafter) for 10-42 days, optionally followed by oral voriconazole/fluconazole. The primary efficacy endpoint was global (clinical and microbiological) response at the end of all therapy (EOT). Secondary endpoints included global response at the end of intravenous therapy (EOIVT) and at 2 and 6 weeks post-EOT, survival at day 90, and incidence of adverse events (AEs). The primary efficacy analysis was performed in the modified intent-to-treat (MITT) population, excluding unknown/missing responses. The safety and MITT populations consisted of 216 and 170 patients, respectively. The most common pathogens were Candida albicans (55.9%), C. glabrata (14.7%) and C. parapsilosis (10.0%). Global success was 69.5% (107/154; 95% CI, 61.6-76.6) at EOT, 70.7% (111/157) at EOIVT, 60.2% (77/128) at 2 weeks post-EOT, and 50.5% (55/109) at 6 weeks post-EOT. When unknown/missing responses were included as failures, the respective success rates were 62.9%, 65.3%, 45.3% and 32.4%. Survival at day 90 was 53.8%. Treatment-related AEs occurred in 33/216 (15.3%) patients, four (1.9%) of whom had serious AEs. Anidulafungin was effective, safe and well tolerated for the treatment of C/IC in selected groups of ICU patients.

Normocapnic high frequency oscillatory hyperventilation increases oxygenation in pigs.

High frequency oscillatory ventilation (HFOV), contrary to conventional ventilation, enables a safe increase in tidal volume (V(T)) without endangering alveoli by volutrauma or barotrauma. The aim of the study is to introduce the concept of normocapnic high frequency oscillatory hyperventilation and to assess its effect upon oxygen gain under experimental conditions. Laboratory pigs (n = 9) were investigated under total intravenous anesthesia in three phases. Phase 1: Initial volume controlled HFOV period. Phase 2: Hyperventilation--V(T) was increased by (46 +/- 12) % when compared to normocapnic V(T) during phase 1. All other ventilatory parameters were unchanged. A significant increase in PaO(2) (by 3.75 +/- 0.52 kPa, p < 0.001) and decrease in PaCO(2) (by -2.05 +/- 0.31 kPa, p < 0.001) were obtained. Phase 3: Normocapnia during hyperventilation was achieved by an iterative increase in the CO(2) fraction in the inspiratory gas by a CO(2) admixture. All ventilatory parameters were unchanged. A significant increase in PaO(2) (by 3.79 +/- 0.73 kPa, p < 0.001), similar to that which was observed in phase 2, was preserved in phase 3 whereas normocapnia was fully re-established. The concept of high frequency normocapnic hyperventilation offers a lung protective strategy that significantly improves oxygenation whilst preserving normocapnia.

Basophil activation can predict clinical sensitivity in patients after venom immunotherapy.

OBJECTIVE: At present, no reliable in vitro test is available to monitor the success of specific venom immunotherapy (VIT) in preventing insect venom anaphylaxis. We investigated usefulness of the basophil activation test (BAT) in predicting the outcome of sting challenge in bee venom-allergic patients after VIT. PATIENTS AND METHODS: Twenty-one patients with bee venom anaphylaxis at the end of VIT and 6 control participants were enrolled. BAT (flow-cytometric evaluation of allergen-induced expression of CD63), skin testing, and specific immunoglobulin (Ig) E determination were performed prior to sting challenge. RESULTS: Five of the 21 patients (23.8%) reacted to sting challenge. At a bee venom concentration of 100 ng/mL, the mean proportion of basophils expressing CD63 was 56% in reactors and 13.2% in nonreactors (P = .0321). Four of the 5 reactors had positive results and 14 of the 16 nonreactors had negative results. Thus, using 18.4% and 21.6% (receiver operating characteristic curve analysis) as the cutoff for expression of the CD63 marker, the positive and the negative predictive values were 67% and 93%, respectively, and specificity and sensitivity for BAT were 80% and 83%, respectively. However, at a concentration of 1000 ng/mL, no significant differences in basophil activation were observed between reactors and nonreactors. CONCLUSION: We found BAT to be a helpful tool in predicting the clinical sensitivity of bee venom-allergic patients after VIT (correlation between BAT at submaximal venom concentration and sting challenge).

[Biochemical and immunohistochemical markers of brain injury]. / Biochemické a imunohistochemické markery poskození mozku.

Proteins released to circulation from affected tissues during primary or secondary trauma brain injury might be used as serum markers of glial or ganglial cells damage (neuron specific enolasis and S100 B protein). Other markers of trauma can be proved as relatively specific of diffuse axonal injury by immunohistochemical detectoin (amyloid prekurzor protein, neuron specific enolasis, glial fibrilar acidic protein and superficial antigen receptor CD 68). Some markers are associated with blood brain barrier damage (matrix metaloproteinases (MMP-2, MMP-9) and synthase of nitric oxide (iNOS)). We aimed in our short communication on biomechanics of developed of trauma, primary or secondary kinds of trauma brain injury and use of trauma brain injury markers for clinical diagnostics and management of patients.

Ultrasound estimation of volume of pleural fluid in mechanically ventilated patients.

OBJECTIVE: The aim was to develop a practical method for estimation of the volume of pleural effusion using ultrasonography in mechanically ventilated patients. DESIGN: Prospective observational study. SETTING: 20-bed general intensive care unit in the university hospital. PATIENTS AND PARTICIPANTS: 81 patients were included after initial suspicion of pleural fluid on chest supine X-ray and pre-puncture ultrasound confirming effusion. Patients with thoracic deformities, post-lung surgery, with diaphragm pathology, haemothorax, empyema and with incomplete aspiration of pleural fluid on post-puncture ultrasound were excluded. INTERVENTIONS: Patients were supine with mild trunk elevation at 15 degrees . Probe was moved upwards in posterior axillary line, and transverse section perpendicular to the body axis was obtained with pleural separation visible at lung base. The maximal distance between parietal and visceral pleura (Sep) in end-expiration was recorded. Thoracentesis was performed at previous probe position and volume of pleural fluid (V) recorded. MEASUREMENTS AND RESULTS: 92 effusions were evaluated and drained; 11 (12%) were excluded for incomplete aspiration. Success rate of obtaining fluid under ultrasound guidance was 100%; the incidence of pneumothorax or bleeding was zero. Mean Sep was 35+/-13 mm. Mean V was 658+/-320 ml. Significant positive correlation between both Sep and V was found: r=0.72; r(2)=0.52; p<0.001. The amount of pleural fluid volume can be estimated with the simplified formula: V (ml)=20 x Sep (mm). Mean prediction error of V using Sep was 158.4+/-160.6 ml. CONCLUSIONS: Easy quantification of pleural fluid may help to decide about performing thoracentesis in high-risk patients, although thoracentesis under ultrasound guidance appears to be a safe procedure.

Normocapnic high-frequency oscillatory ventilation affects differently extrapulmonary and pulmonary forms of acute respiratory distress syndrome in adults.

The recently reported differences between pulmonary and extrapulmonary acute respiratory distress syndromes (ARDS(p), ARDS(exp)) are the main reasons of scientific discussion on potential differences in the effects of current ventilatory strategies. The aim of this study is to assess whether the presence of ARDS(p) or ARDS(exp) can differently affect the beneficial effects of high-frequency oscillatory ventilation (HFOV) upon physiological and clinical parameters. Thirty adults fulfilling the ARDS criteria were indicated for HFOV in case of failure of conventional ventilation strategy. According to the ARDS type, each patient was included either in the group of patients with ARDS(p) or ARDS(exp). Six hours after normocapnic HFOV introduction, there was no significant increase in PaO2/F(I)O2 in ARDS(p) group (from 129+/-47 to 133+/-50 Torr), but a significant improvement was found in ARDS(exp) (from 114+/-54 to 200+/-65 Torr, p<0.01). Despite the insignificant difference in the latest mean airway pressure (MAP) on conventional mechanical ventilation (CMV) between both groups, initial optimal continuous distension pressure (CDP) for the best PaO2/F(I)O2 during HFOV was 2.0+/-0.6 kPa in ARDS(p) and 2.8+/-0.6 kPa in ARDS(exp) (p<0.01). HFOV recruits and thus it is more effective in ARDS(exp). ARDS(exp) patients require higher CDP levels than ARDS(p) patients. The testing period for positive effect of HFOV is recommended not to be longer than 24 hours.

Prostacyclin versus citrate in continuous haemodiafiltration: an observational study in patients with high risk of bleeding.

BACKGROUND: The efficacy and safety of prostacyclin (PGI2) and citrate (ACD) anticoagulation were observed and compared during continuous haemodiafiltration. METHODS: Mechanically ventilated patients received either the PGI2 analogue epoprostenol (group A, n = 17) in escalating doses of 4.5-10.0 ng.kg(-1).min(-1) in combination with heparin (6 IU.kg(-1).h(-1)) or 2.2% ACD (group B, n = 15). Blood flow was set to match the circuit-filling volume per unit time equal to the intravascular half-life of PGI2. RESULTS: Median filter lifetimes were 26 h (interquartile range 16-37) in group A (39 filters) and 36.5 h (interquartile range 23-50) in group B (56 filters; p < 0.01). In group A, 4 patients (23.5%, p < 0.05) had the dose reduced due to hypotension. The final mean dose of PGI2 was 8.7 +/- 2.4 ng.kg(-1).min(-1). Four patients in group A (23.5%, p < 0.05) were switched to ACD due to a decrease in platelet count. No bleeding episodes, decrease in platelet count or adverse haemodynamic effects were encountered in group B. The cost of epoprostenol plus low dose heparin (EUR 204.73 +/- 53.04) was significantly higher than the cost of ACD-based anticoagulation (EUR 93.92 +/- 45.2, p < 0.05). CONCLUSION: ACD offers longer filter survival, has no impact on platelet count and is less expensive. Increasing the dose of PGI2 up to the average of 8.7 ng.kg(-1).min(-1) did not increase the haemodynamic side effects.

Can bioimpedance determine the volume of distribution of antibiotics in sepsis?

The relationship between the volume of distribution, assessed according to the two-compartmental pharmacokinetic model, and extracellular water estimated by bioimpedance was studied in mechanically ventilated patients with sepsis and capillary leak. A prospective observational study was performed in a twenty-bed general intensive care unit in the university hospital. Patients received either vancomycin (n = 16) or netilmicin (n = 12) for more than 48 hours. Those with ascites, pleural effusion, on renal replacement therapy or with haemodynamic instability were excluded. Serum concentrations of drugs were taken for pharmacokinetic analysis before, 1 hour and 4 hours after the 30 minute infusion. Bioimpedance measurement was performed at the time of the third sampling. The protocol was repeated after 24 hours. Fluid balance during the 24 hour interval was recorded. Extracellular water was increased and represented 45.6 to 46.6% of total body water Fluid balance correlated with the change of extracellular water (r = 0.82, P < 0.0001) and total body water (r = 0.74, P < 0.0001). Volumes of distribution of vancomycin (0.677 +/- 0.339 l/kg) and netilmicin (0.505 +/- 0.172 l/kg) were increased compared to normal values. A correlation was demonstrated between volume of distribution (Vd(area)) of vancomycin and extra cellular water/total body ratio (r = 0.70, P < 0.0001). The central compartment distribution volume (V1) of netilmicin correlated with extracellular water/total body water ratio (r = 0.60, P < 0.003). Serum concentrations above the recommended therapeutic range were detected in 81.2% of patients on vancomycin and in 50% of patients on netilmicin. Increased volumes of distribution can be estimated by the bioimpedance measurements but are not associated with requirements for higher dosage of the glycopeptide or aminoglycoside antibiotics.

The effect of subarachnoid sodium nitroprusside on the prevention of vasospasm in subarachnoid haemorrhage.

OBJECTIVE: The aim of this study was to evaluate the effect of preventive and therapeutic use of subarachnoid sodium nitroprusside (SNP) administration in patients with non-traumatic subarachnoid haemorrhage (SAH). METHODS: All consecutive adult patients admitted in the period 2000-2003 with SAH, Hunt-Hess grade I-IV, indicated for neurosurgical intervention, were enrolled in the study. In the postoperative period they were treated with mechanical ventilation and triple H protocol with nimodipine. Subarachnoid preventive SNP was administred in initial dose of 1 mg by catheter inserted into basal cisterns during the neurosurgical procedure. The timing of following dosage was directed by the changes of respiratory parameters of brain tissue in the region of interest by multiparameter sensor (Codman Neurotrend) and findings of blood flow velocity on the level of circle of Willis were measured by transcranial doppler ultrasonography (TCD). RESULTS: 17 patients were enrolled to study. All patients survived. No brain infarction developed. The increase blood flow velocity was found in three patients. CONCLUSION: Preventive subarachnoid use of SNP in combination with multimodal monitoring might be a possible preventive strategy. Its efficacy has to be proved on a greater group of patients in the future. The therapeutical use of SNP requires an increase in application rate.

Apoptosis as an early event in the development of multiple organ failure?

We have recently developed a simple method of plasma free DNA detection, which enables us to distinguish between apoptotic and genomic (necrotic) DNA. After applying this method to the critically ill, we revealed apoptotic DNA on the day of admission to be higher than later when multiple-organ failure developed. Moreover, apoptotic DNA contributed to total plasma DNA much more than DNA from necrotic cells and its increase predicted future development of multiple-organ failure and death.

Higher content of 18:1 trans fatty acids in subcutaneous fat of persons with coronarographically documented atherosclerosis of the coronary arteries.

AIM: To identify the total content of trans fatty acid (TFA) isomers and C18:1 trans isomers in subcutaneous fat samples from persons with atherosclerosis of the coronary arteries, as an indicator of dietary exposure. METHODS: Using capillary gas chromatography, the authors determined total content of TFA isomers and C18:1 trans isomers in the subcutaneous fat of 34 patients with ischemic heart disease who had undergone aortocoronary bypass surgery and in 46 patients with no sign of coronary disease. RESULTS: On average, the total TFAs in cardiac patients were 2.88 +/- 1.19% of all fatty acids, in noncardiac patients 2.56 +/- 0.89%. However, the difference is not statistically significant. The average concentration of C18:1 trans in cardiac patients (2.31 +/- 1.09%) was statistically significantly higher (p = 0.05) than in the noncardiac group (1.95 +/- 0.77%). CONCLUSIONS: The results obtained indicate a lower TFA load in comparison with previous studies in other countries. A higher concentration of 18:1 TFAs in the subcutaneous fat of patients with coronary disease might be an impulse to correct the dietary habits of this very high-risk population.

[Infiltration of local anesthetics into the thyroid gland capsule for surgery and the postoperative period]. / Prínos infiltrace pouzdra stítné zlázy lokálním anestetikem pro operacní a bezprostrední pooperacní prubeh.

In a prospective randomized study the hypothesis was tested whether infiltration of the thyroid capsule by a local anaesthetic will reduce the haemodynamic response to surgical trauma, consumption of anaesthetics and opioids during surgery and will shorten the time of arousal. A total of 64 patients indicated for planned goitre surgery were divided at random into a control group (C, n = 32) and experimental group (LA, n = 32). The preoperative medication and anesthesia did not differ in the two groups. In group C into the thyroid capsule a maximum of 40 ml saline was administered, in LA the same volume of 0.5% trimecain. A highly significant difference was found (p < 0.001) in the incidence of hypertension during surgery (21 C vs. 5 LA) and the need of further pharmacological interventions (21 vs. 8). In the control group was a higher consumption (p < 0.95) of the opioid phentanyl (167.5 +/- 111 micrograms vs. 125 +/- 93.5 micrograms), a trend of longer arousal and the need to antagonize the effect of opioid (p < 0.1). The substitution of saline by a local anaesthetic for infiltration of the thyroid capsule is a safe and simple method leading to a reduction of cardiovascular complications during surgery.

[Hypocholesterolemia after multiple injuries is not caused by simple hemodilution]. / Hypocholesterolemie po polytraumatu není zpusobena prostou hemodilucí.

The authors examined in 45 patients with multiple injuries total serum cholesterol levels and the packed cell volume on admission, 24 hours and 48 hours after injury. The cholesterol level in these patients declined as compared with a control group to 0.61 on admission of the patient (on average 102 min. after injury) and to 0.51 and 0.53 24 and 48 hours after injury, while the packed cell volume declined to 0.76 on admission and to 0.64 24 and 48 hours after the injury. The lose correlation between cholesterol and the packed cell volume (r2 = 0.27) suggests the part played by another mechanism of development of hypocholesterolaemia in patients with multiple injuries than mere haemodilution. In eight patients who died no correlation with hypocholesterolaemia was found.

[Contusion of the lungs in childhood]. / Kontuze plic v detském veku.

The authors evaluated in a retrospective study a group of 45 patients with contusion of the lungs (age 1 to 15 years) who were treated at the Faculty Hospital in Motol in 1989-1993. In 38 children contusion of the lungs was part of multiple injuries with signs of failure of vital functions. These children were admitted after the injury to the in-patient department of the Anaesthesiological and Resuscitation Clinic. Seven children without alterations of vital functions were treated at the Department of Paediatric Surgery. The diagnosis was based on the case-history, clinical examination, X-ray examination and laboratory signs of lung injuries. An isolated pneumothorax was found in 17.8% of the injured children, haemothorax in 8.9% and in 24.5% pneumothorax and haemothorax. Severe craniocerebral injuries were diagnosed in 71% of patients, 37.8% children had concomitant injuries of the abdominal organs and retroperitoneum and 42% had fractures of the long bones. 46.6% of the children had rib fractures. The condition of 35 injured children called for endotracheal intubation (on average for 17 days) and artificial ventilation (on average for 14.4 days). 98% of the injured children were given antibiotics, in 84% steroids were administered, in 18 of the injured children (40%) drainage of the thoracic cavity was essential. Six patients (13.3%) drainage of the thoracic cavity was essential. Six patients (13.3%) died--the cause of death were severe injuries of the CNS.

[Hepatic resection technique in children]. / Technika resekce jater v detském veku.

The authors present their experience with resection of the liver in children. In 1986-1993 they performed a total of 34 major resections of the liver. The mean age of the operated children was 4 years and 5 months, the youngest patient was operated at the age of 4 days and the oldest one at the age of 17 years. The group was divided into two time periods which are compared, because in 1990 the authors changed their surgical tactics and technique and also the procedure used for general anaesthesia. During the first period/1986-1989/they made 12 resections of the liver and during the second period/1990-1993/22 resections. The two groups of patients are compared as regards mortality during operation, early and late deaths. In the first period the mortality was 25%, in the second period no death occurred during operation. Early deaths were recorded during the first period in 25%, during the second period in 4.5%. Patient survival during the first period is 33% and during the second period 86.5%. The authors describe the technique of resection of the liver they use at present with emphasis on isolation of the vena cava inferior with the possibility of easier control of haemorrhage and the use of an ultrasonic aspirator/CUSA/and laser during resection proper which makes easier identification of hepatic structures and control of blood losses on operation possible. In malignant tumours the radicality of surgery increased as manifested on patient survival. From the first period 15% patients survive, from the second period 83% without signs of relapse.