Cardiorespiratory effects of change in posture after spinal anesthesia with hyperbaric bupivacaine.

Spinal anesthesia is a special regional anesthetic technique that is applied in lower limb orthopedic and other surgical procedures made below the transverse umbilical line, which is able to produce a neuraxial central block. The patient's position, together with the baricity of the drug solution injected, is a variable that can affect the success of anaesthesia. According to clinical practice, lateral decubitus or the sitting position are to be maintained for a period ranging from 15 to 20 minutes to avoid any possible motion of the injected solution that could cause side effects due to anesthetic being distributed up to thoracic segments. We describe a case of cardiovascular and respiratory effects occurred approximately 65 min after spinal anesthesia with 7 mg of 1% hyperbaric bupivacaine in a patient during change in posture from mild anti-Trendelemburg to supine decubitus. These findings show that a change in posture after spinal anaesthesia with hyperbaric bupivacaine can affect the safety of this anesthesia technique, also after a longer period of time than is usually recommended to avoid the spread of anaesthetic drug.

The aged patient who has undergone an operation in the intensive care unit.

The reaching of 13% within the Italian population of those who are older than 70 has caused a significant rise in the number of the elder people who undergo major surgery operations; this is due also to the availability of mini-invasive endo-laparoscopic techniques, to the availability of new very manageable anaesthetics and new anaesthesia plans, suitable for the elder, to a more effective control of post-operative pain, and mostly to a comfortable access to I.C.U. in the post-operative phase.

Ozonized autohaemotransfusion and fibrinolytic balance in peripheral arterial occlusive disease.

The acute effects of a major ozonized autohaemotransfusion on blood fibrinolytic capacity were evaluated in 20 subjects affected by peripheral arterial occlusive disease (PAOD). The parameters examined were tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1). In subjects not previously submitted to autohaemotransfusion ('unaccustomed' subjects), whether they were PAOD patients or healthy volunteers, the PAI-1/t-PA ratio in the blood samples taken 15 min before the autohaemotransfusion was higher (P < or = 0.05) than at baseline. These changes were independent of the presence of ozone in the autohaemotransfusion blood. Values in both healthy and PAOD-affected individuals were again at baseline 120 min after the end of autohaemotransfusion. In PAOD patients and in healthy subjects previously submitted to several autohaemotransfusions ('accustomed' subjects), the PAI-1/t-PA ratio did not significantly change before, during and after an additional autohaemotransfusion. The results (the increased heart rate and epinephrine and norepinephrine urinary excretion only in non-accustomed subjects) suggest that the acute fibrinolytic imbalance is caused by the apprehensive state produced by the procedure in unaccustomed subjects. Autohaemotransfusion with ozonized blood per se does not significantly influence the fibrinolytic balance.

Biomolecular and biochemical response of myocardial cell to ischemia and reperfusion in the course of heart surgery.

BACKGROUND: Previous studies have shown that biomolecular and biochemical adaptive changes antagonize oxidative damage due to hypoxia and ischemia in myocardial cells. The aim of our study was to verify in human ischemic and reperfused cardiac tissue the relationship between mitochondrial enzyme activities and the activation of HSP70 and c-fos syntheses in the context of a cytoprotective mechanism. Nitric oxide (NO) modulating effects on mitochondrial respiratory chain enzyme activities in ischemic and reperfused tissue were investigated (preliminary report). METHODS: During elective coronary artery bypass grafting, in 30 consecutive patients ventricle samples were taken one before aortic clamping the second after 55+/-8 min ischemic period and the third 34+/-5 after final reperfusion. Coronary sinus blood samples were taken in parallel to assess free radical release measured by malonaldehyde (MDA) levels. In a small number of patients (N=5) nitric oxide tissue levels were analyzed. RESULTS: When compared with normoxic tissue, a significant decrease in cytochrome Coxidase (COX) and succinate Cyt-c reductase (SCR) activities in ischemic and reperfused samples were observed. The activation of HSP70-72 and c-fos transcription factor was evident in courses of ischemia and reperfusion. Blood MDA levels underline the concept that oxyradical generation characterize the peroxidative damage in reoxygenated myocardial tissue while adaptive changes which occur in ischemic cells seem to antagonize the oxyradical injury. CONCLUSIONS: In the course of heart surgery the myocardial cell seems to prevent ischemic damage by activating some peculiar biomolecular and biochemical adaptive changes which permit the reversibility of the oxidative injury. In contrast it appears evident that massive and rapid reoxygenation of the cardiac tissue leads to peroxidative damage due to oxyradical generation. Nitric oxide seems to play a crucial role in cellular adaptation to ischemia even if further studies will be needed to elucidate these findings. From the data obtained in this work we cannot draw certain conclusions in terms of human cardiac cell adaptation to ischemia whereas it seems convincible that reoxygenation, as actually employed in clinical practice, compromises the integrity of the cells.

Cardiogenic shock and L-carnitine: clinical data and therapeutic perspectives.

Research experiences on the use of L-carnitine in conditions of acute hypoxia underline the protective role of this molecule on the cellular enzymic complex. To obtain unconfutable clinical data at this regard, the survival rate in two groups of patients affected by cardiogeic shock was evaluated. The first group (80 patients) was treated with L-carnitine while the second group (36 patients) received sodium bicarbonate. The results showed a significant response to L-carnitine treatment, indicating the role of this molecule on the metabolic acidosis due to shock. The sum of these data confirmed the role of L-carnitine in the reversible phase of cardiogenic shock in terms of enzymic protection in the course of cellular oxidative damage.

Caval filters in intensive care: a retrospective study.

AIM: To evaluate the effectiveness of a caval vein filter (CVF) peri-implant monitoring protocol in order to reduce pulmonary embolism (PE) mortality and CVF-related morbidity. BACKGROUND: The reduction in mortality from PE associated with the use of CVF is affected by the risk of increase in morbidity. Therefore, CVF implant is a challenging prophylactic or therapeutic option. Nowadays, we have many different devices whose rational use, by applying a strict peri-implant monitoring protocol, could be safe and effective. MATERIALS AND METHODS: We retrospectively studied 62 patients of a general Intensive Care Unit (ICU) scheduled for definitive, temporary, or optional bedside CVF implant. A peri-implant monitoring protocol including a phlebocavography, an echo-Doppler examination, and coagulation tests was adopted. RESULTS: In our study, no thromboembolic recurrence was registered. We implanted 48 retrievable and only 20 definitive CVFs. Endothelial adhesion (18%), residual clot (5%), cranial or caudal migration (6%), microbial colonization of the filter in the absence of clinical signs of infection (1%), caval thrombosis (1%), and pneumothorax (1%) were reported. Deep-vein thrombosis (DVT) was reported (8%) as early complication. All patients with DVT had a temporary or optional filter implanted. However, in our cohort, definitive CVFs were reserved only to 32% of patients and they were not associated with DVT as complication. CONCLUSION: CVF significantly reduces iatrogenic PE without affecting mortality. Generally, ICU patients have a transitory thromboembolic risk, and so the temporary CVF has been proved to be a first-line option to our cohort. A careful monitoring may contribute to a satisfactory outcome in order to promote CVF implant as a safe prophylaxis option.

Effect of autonomic nervous system dysfunction on sudden death in ischemic patients with anginal syndrome died during electrocardiographic monitoring in Intensive Care Unit.

AIM: The aim of this study was to investigate the role of sympathovagal imbalance in patients with ''ischemic'' sudden death (arrhythmic death preceded by ST segment shift). Although heart rate variability is a powerful tool for risk stratification after myocardial infarction, the mechanism precipitating sudden death is poorly known. METHODS: We analyzed the records of 10 patients who had ischemic sudden death during ECG Holter monitoring. Thirty patients with angina and transient myocardial ischemia during Holter monitoring served as control subjects. Arrhythmias, ST segment changes and heart rate variability were analyzed by a computed interactive Holter system. RESULTS: In 8 patients the sudden death was induced by ventricular fibrillation; in 2 by atrioventricular block followed by sinus arrest. All 10 patients showed ST segment shift. ST depression (maximal change 0.54+/-0.16 mV) occurred in 6 patients and ST elevation (maximal change 0.65+/-0.24 mV) in 4. The standard deviation of normal RR intervals (SDNN) was 92+/-30 ms during total Holter monitoring period vs 70+/-10 ms and 46+/-8 ms in epoch 1 and epoch 2 respectively. The SDNN was lower before the occurrence of ischemic sudden death: 54+/-12 ms (P< 0.005) in epoch 3 and 26+/-5 (P<0.005) in epoch 4 (i.e. 5 min before the onset of fatal ST segment shift). In controls the SDNN was 108+/-30 ms during total Holter monitoring period, whereas is measured 58+/-28 ms 5 min before the most significant episode of ST shift vs 26+/-5 in the group with sudden death (P<0.001). CONCLUSION: Sympathovagal imbalance, as detected by a marked decrease in heart rate variability, is present in the period (5 min) immediately preceding the onset of the ST shift precipitating ischemic sudden death. These findings suggest that transient autonomic dysfunction may facilitate, during acute myocardial ischemia, fatal arrhythmias precipitating in sudden death.

Mitochondrial genome involvement in ischemia/reperfusion-induced adaptive changes in human myocardial cells.

AIM: Following previous studies on the ischemia-induced adaptive changes in human cardiac mitochondria, we examined in the present paper the interaction between nitric oxide-induced (NO) partial inhibition of Cyt. c oxidase (Cyt.OX) and mitochondrial encoded subunit 2 expression. Aim of the study was to investigate specific stages of the biochemical and molecular cascade which takes place in cytoprotective mechanisms of ischemic and reperfused cardiac cell. METHODS: We examined human left ventricle samples obtained from 20 patients undergoing elective valve surgery before aortic cross-clamping, 20+/-2 min (prolonged ischemia), 58+/-5 min after cross-clamping (intermittent ischemia) and 21+/-4 min after reconstitution of coronary blood flow (reperfusion). Cyt.OX activity was determined by spectrophotometric method and adenosine triphosphate (ATP) content using bioluminescent assay. Malondialdehyde (MDA) assumed as reactive oxygen species (ROS) generation marker was determined by high-performance liquid chromatography method. On the same cardiac samples mitochondrial encoded Cyt.OX subunit 2 expression was examined by immunoblot analysis and blu native gel electrophoresis method. Statistical study of obtained data was performed using repeated measures analysis of variance (ANOVA). RESULTS: Prolonged as well intermittent ischemia caused reduction of Cyt.OX activity and ATP, a moderate accumulation of ROS and down-regulation of Cyt.OX subunit 2. When reperfused the cardiomyocytes showed a progressive increase of Cyt.OX activity, ATP pools and Cyt.OX subunit 2 expression. ROS generation was significantly increased by the rapid oxygen re-immission in the cardiac cell. CONCLUSIONS: These data confirm the suggestion that prolonged as well as intermittent ischemia induces activation of cytoprotective mechanisms crucial for cardiac cell survival. Indeed, co-ordinated down-regulation of Cyt.OX activities, ATP pools and mitochondrial encoded Cyt.OX subunit 2 are in favour of an ischemia-activated adaptive mechanism leading to transient and reversible oxidative injury. This observation is confirmed by reduction of apoptosis molecular markers and by complete recovery of mitochondrial oxidative activities in reperfused cardiac tissue.

Mechanisms of cell protection by adaptation to chronic and acute hypoxia: molecular biology and clinical practice.

Several experimental and clinical studies have shown that specific biochemical and molecular pathways are involved in the myocardial and skeletal muscle cell tolerance to acute and/or chronic hypoxic injury. A number of different factors were proposed to play a role in the preservation of tissue viability, but to a few of them a pivotal role in the adaptive mechanisms to hypoxic stimuli could be ascribed. Starting from the observation that mitochondrial electron transport chain (ETC) enzymic complexes are the targets of oxygen reduced availability, most of data are compatible with a mechanism of enzymic adaptation in which the nitric oxide (NO) generation plays the major role. If the partial and reversible NO-induced inhibition of ETC enzymic complexes represents the most rapid and prominent adaptive mechanism in counteracting the damaging effects of hypoxia, the sarcolemmal and mitochondrial K+(ATP) channels activation results to be closely involved in cytoprotection. This process is depending on protein kinase C (PKC) isoform activation triggered by reactive oxygen species (ROS) generation, adenosine triphosphate (ATP) depletion and Ca++ overload. It is well known that all these factors are present in hypoxia-induced oxidative damage and mitochondrial Ca++ altered pools represent powerful stimuli in the damaging processes. The activation of mitochondrial K+(ATP) channels leads to a significant reduction of Ca++ influx and attenuation of mitochondrial Ca++ overload. Closely linked to these adaptive changes signal transduction pathways are involved in the nuclear DNA damage and repair mechanisms. On this context, an essential role is played by the hypoxia-induced factor-1alpha (HIF-1alpha) in terms of key transcription factor involved in oxygen-dependent gene regulation. The knowledge of the biochemical and molecular sequences involved in these adaptive processes call for a re-evaluation of the therapeutic approach to hypoxia-induced pathologies. On this light, some specific aspects of the therapeutic management of critically ill patients are taken into consideration and discussed in relation to the cellular biodynamics.

[Hypomagnesemia and hypokalemia as risk factors of arrhythmia in acute phase myocardial infarction]. / Ipomagnesemia e ipokalemia come fattori di rischio aritmogeno nell'infarto del miocardio in fase acuta.

In a uniform group of 30 patients the A. have assessed the incidence of lower serum K+ and Mg++ concentrations on the probability of arrhythmias onset in the acute phase of myocardial infarction. The study shows that lower K+ and Mg++ levels significantly influence only the onset of ventricular tachycardia and monofocal PVC.

Signal transduction mechanisms and nitric oxide in hypoxic and ischemic human cardiac ventricular cell.

BACKGROUND: Nitric oxide (NO) plays a well-known role in regulating endocellular adaptive changes to acute hypoxia and ischemia. The reversible inhibition of complex IV of the mitochondrial respiratory chain fulfils a cytoprotective function, whereas the progressive inhibition of complex I and II reveals the onset of irreversible oxidative damage due to persistent NO production in response to prolonged hypoxia and/or ischemia. In hypoxic or ischemic human myocardial cells, death may be caused by apoptosis or necrosis following the activation of the biomolecular signal transduction mechanisms. The activation of MAPK (mitogen-activated protein kinase) followed by ERK (extracellular regulated kinase) and p21waf is necessary in this respect. The myocardial cell is well known for its postmitotic nature and through their activation these kinases aim to repair DNA damaged by oxidative stress in order to guarantee the survival of the cell itself. A direct correlation has been found between the activation of these kinases and NO production. It was decided to carry out this study in hypoxic and ischemic human heart ventricular tissue in order to confirm this connection. METHODS: In 10 patients undergoing cardiac valvular replacement, ventricular samples were collected before aortic clamping, after 15 min of ischemia and after 60 minutes during which the patients received doses of hematic cardioplegic solution at regular intervals. RESULTS: The results show a rapid increase in NO production in response to ischemia followed by a tendency for levels of this element to fall. MAPK, ERK and p21waf activation was parallel to No production, irrespective of the repeated administration of hematic cardioplegic solution. The heart tissue examined 60 minutes after aortic clamping came from a ventricular area subject to preconditioning mechanisms. In view of this, the data obtained must be seen in terms of the close correlation between the mitochondrial action played by NO and the contemporary and consequent activation of unique signal transduction mechanisms. CONCLUSIONS: This may prove important to our understanding of preconditioning mechanisms involving the myocardial and confirms the role played by the said kinases with regard to the survival of hypoxic and ischemic human heart tissue. Although not final, these deductions may be important in clinical and therapeutic terms for the management of critical patients.

[Biochemical and metabolic aspects of oxyradical pathology in the hypoxic-ischemic reperfused human skeletal muscle tissue. Clinical markers and therapeutic approach]. / Aspetti biochimici e metabolici della patologia ossiradicalica nel muscolo scheletrico umano ipossico-ischemico-riperfuso. Parametri valutativi nella clinica e nella terapia del paziente critico.

BACKGROUND: Following our previous studies on the biomolecular and biochemical aspects of the human tissue oxidative damage due to hypoxia, ischemia and reperfusion, aim of the present work is to evaluate the role played by oxyradical generation in the morphofunctional cellular injury. We evaluated the tissue levels of some metabolic markers (MDA, Catalase, Uric Acid) to obtain a pathogenic picture and then a therapeutic approach closely related to the cellular biodynamics. METHODS: A skeletal muscle samples were taken during elective knee orthopedic surgery in 20 consecutive patients. The biopsies were taken in normoxic conditions and after 5 +/- 1 and 62 +/- 3 min form tourniquet application and finally 21 +/- 2 min following muscle reperfusion. The samples were assayed for tissue Malondialdeyade (MDA), uric acid and catalase (CAT) contents with HPLC and fluorimetric procedures. All data were evaluated in terms of computerized statistical analysis. RESULTS: When compared to normoxic tissue (1.24 +/- 0.26 nmoli.mg-1 protein), the MDA levels show a moderate increase in hypoxic (1.66 +/- 0.12) and ischemic tissue (1.78 +/- 0.13), while highly significant is the rise in reperfused muscle MDA content (5.94 +/- 0.15). The uric acid as far as CAT shows no appreciable alterations in hypoxia and ischemia. Following reoxygenation an increase in uric acid contents with a concomitant CAT tissue consumption appear evident. CONCLUSIONS: The obtained data seem to underline the cytoprotective role played by adaptive changes in the hypoxic and ischemic human cells. On the contrary, the rapid reoxygenation of the ischemic tissue appears to start oxyradical neo-generation. In clinical and therapeutic terms these observations underline a peculiar and different approach to the critically ill patient.

Deep sedation for magnetic resonance imaging. Personal experience.

AIM: Precision in diagnostic procedure and examination of paediatric patients often requires their absolute immobility. Deep sedation has proven to be an excellent method, allowing optimum technical quality of MRI particularly in younger age groups. The aim of study is to demonstrate the possible application of deep sedation through the use of 2 safe and manageable drugs. METHODS: We carefully evaluated and selected 82 patients (47 males and 35 females; average age 5.4 years): they came from various paediatrics departments. Deep sedation was practiced with: Chloral hydrate (60-80 mg/kg in one oral administration); propofol as intravenous bolus (2-2.5 mg/kg) followed by a maintenance infusion of 75-125 microg/kg/min. This was preceded by midazolam (0.05 mg/kg i.v.) outside the MRI room. Oxygen saturation (SpO2) was monitored in all patients along with heart rate in order to foresee the need for any possible therapeutic intervention. RESULTS: The sedation levels attained permitted the success of MRI assuring the immobilization required. Manually assisted mask ventilation was required for a period of 2-3 min in 5 patients treated with propofol. All other patients breathed autonomously. Complete reawakening occurred within 2 hours of drug administration. Surveillance was prolonged inside their respective units, however, without registering delayed side effects. CONCLUSION: The central point of the success of deep sedation is to define the type and dose of optimum drug for individual patients. This requires a qualified, expert group ready to intervene in the presence of adverse results of drugs administered. Propofol and chloral hydrate are the optimum drugs for diagnostic techniques requiring total immobilization and rapid reawakening.

Elevated plasma free fatty acid concentrations do not modify cardiac repolarization in patients treated by electrolyte-glucose-insulin infusion.

Fat emulsion infusion is routinely used as a source of calories and essential fatty acids for critically ill patients who may be at risk for acquired ventricular repolarization alterations due either to drugs or electrolyte disturbances. The aim of this study was to evaluate whether acute elevations of plasma free fatty acid concentrations influence the corrected Q-T interval (Q-Tc), Q-Tc dispersion and sympathetic nervous system activity in patients requiring parenteral nutrition. Thirty hospitalized patients (mean +/- SD: 62 +/- 17 yr of age) requiring total parenteral nutrition received an infusion of 10% (500 ml) triacylglycerol emulsion as a source of calories (450 Kcal); on another occasion, and in random order, the same patients received an infusion of 20% (500 ml) triacylglycerol emulsion (900 Kcal). The infusion lasted 8 h and was preceded by a sc injection of heparin (5,000 U). Infusions of both 10% and 20% triacylglycerol emulsion increased plasma free fatty acid (p<0.00 1) and triacylglycerol (p<0.01) concentrations, and was associated with no significant change in mean BP, heart rate, and plasma catecholamines. At baseline, Q-Tc and Q-Tc dispersion were within the normal range (<440 milliseconds for QTc and <40 ms for QTc-d) and did not show any significant change at any time during infusion of triacylglycerol emulsion at both concentrations. In the setting of a balanced parenteral nutrition, acute elevation of plasma free fatty acid concentrations in critically ill patients do not modify ventricular repolarization.

[The nitric oxide metabolism in the hypoxic, ischemic and reperfused human skeletal muscle cell: clinical and therapeutical observations]. / L'ossido nitrico nella cellula muscolare umana ischemica e riperfusa: connessioni cliniche e terapeutiche.

BACKGROUND: The biochemical and metabolic role played by nitric oxide (NO) in course of oxidative stress due to cell hypoxia, ischemia and reperfusion has a determinant relevance in the mitochondrial adaptive changes which antagonize the irreversible morpho-functional damage. In particular conditions, such as in prolonged ischemia and/or exogenous NO supplementation, this element is present in the radical form (NOO*) concurring to peroxidative cell injury. Aim of this study was to investigate these opposite NO aspects in hypoxic, ischemic and reperfused human skeletal muscle tissue. METHODS: Skeletal muscle samples were taken during elective knee orthopedic surgery in 10 consecutive patients. The biopsies were obtained before, after 5+/-1 min and 58+/-2 min from tourniquet application and then after 18+/-3 min following muscle reperfusion. The samples, immediately frozen in liquid nitrogen, were assayed for endocellular free NO following the gas-amperometric method described by Palmerini C. RESULTS: When compared with normoxic tissues, a significant decrease in free NO content was observed in hypoxic samples. After about 60 min of prolonged ischemia the NO levels show an evident increase, while the tissue reperfusion leads to a progressive restoration of physiological content in the cellular free nitric oxide. CONCLUSIONS: The obtained data in hypoxic muscle cell seem to underline the pivotal role played by NO in adapting the cytochrome c oxidase oxidative activity to lower O2 bio-availability. On the other hand the prolonged ischemia leads to a consistent NOO* generation triggered by oxyradical generation and Ca2+ intracellular over load. Even if the tissue reoxygenation restores the normal NO levels it is arguable that the pre-treatment of ischemic cell with antioxidants, Ca-antagonist and Dexamethasone supplementation could represent a crucial and specific therapeutic approach to critically ill patient.