Evaluation of cystatin C with iohexol clearance in cardiac surgery.

BACKGROUND: Post-operative renal dysfunction after cardiac surgery is not uncommon and can lead to adverse outcome. The ability to accurately monitor renal function is therefore important. Cystatin C is known to be a sensitive marker of the glomerular filtration rate (GFR), but it has not been fully evaluated in cardiac surgery. Iohexol clearance is considered a reliable reference method for the determination of GFR. The aim of this study is to, for the first time, evaluate the diagnostic accuracy of plasma cystatin C compared with iohexol clearance in cardiac surgery. METHODS: Twenty-one patients scheduled for elective coronary artery bypass grafting were prospectively enrolled in the study. Before surgery and on the second post-operative day, an iohexol clearance was performed. Plasma cystatin C, plasma creatinine and plasma C-reactive protein were determined before surgery and on the first, second, third and fifth post-operative day. Estimated creatinine and cystatin C clearances were determined. RESULTS: Post-operative cystatin C and 1/cystatin C correlated strongly to iohexol clearance (r=-0.90 and 0.86) and so did creatinine and 1/creatinine (r=-0.83 and 0.78). Estimated creatinine clearance differed from iohexol clearance (P<0.01), whereas estimated cystatin C clearance did not differ from iohexol clearance (P=0.81). No correlation was found between C-reactive protein and cystatin C. CONCLUSION: This study indicates that clearance estimations based on cystatin C are more accurate compared with estimations based on creatinine in determining GFR in cardiac surgery. Cystatin C has, in this study population, a stronger correlation to iohexol clearance than creatinine.

A retrospective study on the microbiology in patients with oral complaints and oral mucosal lesions.

OBJECTIVE: The aim of this study was to microbiologically analyze oral mucosal samples collected during 2 years from patients with oral mucosal complaints. MATERIALS AND METHODS: Mucosal scraping samples were taken from 297 patients and semiquantified by culture for detection of opportunistic microorganisms e.g. Staphylococcus aureus, enterococci, aerobic Gram-negative bacilli (AGNB) and yeasts. Antibiotic susceptibility test was performed. RESULTS: Altogether 297 patients were sampled (mean age 56.8 +/- 20.7). Among the 110 patients with known medical condition, 48 were systemically immunocompromised, 35 had systemic diseases, and 27 had only local oral complaints. Opportunists in moderate growth or more were present commonly in all three groups and most frequent in the immunocompromised patients (66.7%). Candida species were the most frequent opportunist (68.8%), however, their level was low and combinations with bacterial opportunists were common (39.6%). All bacterial opportunists tested were antibiotic multiresistant. Follow-up samples were collected in 23 cases out of which seven showed still presence of opportunists in heavy growth despite repeated treatment with ciprofloxacin. CONCLUSIONS: This study showed a frequent presence of bacterial and fungal opportunists in patients with oral mucosal complaints, which were most common in immunocompromised individuals, however, also frequent in patients with local oral complaints only. Systematic evaluation of different treatment strategies is needed.

Effects of NO inhalation on pulmonary leukocyte sequestration and blood volume in porcine endotoxaemia.

OBJECTIVE: Sequestration and migration of activated neutrophils plays a major role in the pulmonary injury typical of septic shock and the adult respiratory distress syndrome. Inhaled NO may counteract alveolar-capillary damage attributed to activated neutrophils. The present study describes a method to directly demonstrate the effects of NO inhalation on endotoxin-induced sequestration of 99mTc-labelled leukocytes [As(t)] in the lungs of pigs. DESIGN: Prospective controlled study. SETTING: Laboratory for experimental surgery at a university medical centre. SUBJECTS: Anaesthetised and ventilated pigs. INTERVENTIONS: To induce inflammatory shock 26 animals received a continuous endotoxin infusion. Thirteen animals inhaled NO from the start of the experiments, while 13 served as controls. In 13 animals from both groups, leukocytes were labelled in vitro and reinjected, while in the 13 others erythrocytes were labelled in vivo to provide corrections for changes in blood volume. MEASUREMENTS AND RESULTS: The pulmonary distribution of 99mTc-labelled leukocytes or erythrocytes was studied dynamically for 180 min. After correction for changes in pulmonary and heart blood volume (PBV, HBV), leukocyte sequestration curves were generated. Endotoxin induced pulmonary vasoconstriction, reduced PBV, impaired oxygenation, and caused a maximum increase in As(t) of 30% in the lungs. NO inhalation attenuated pulmonary vasoconstriction and the reduction in PBV. The maximum increase in As(t) was reduced to 15% of baseline. CONCLUSIONS: Inhaled NO exerts its main vascular effects in the pulmonary microvasculature, the primary site of physiological neutrophil margination and pathological adhesion of activated leukocytes. Early use of NO inhalation may offer protection against the development of more lasting pulmonary failure in septic shock by reducing leukocyte sequestration in the lungs.

Elastic pressure-volume curves of the respiratory system reveal a high tendency to lung collapse in young pigs.

OBJECTIVE: To study pressure-volume (P/V) curves over a wide pressure and volume range in pigs. DESIGN: Dynamic and static P/V curves (P(dyn)/V and P(st)/V) and compliance of the respiratory system were studied. The effects of recruitment, positive end-expiratory pressure (PEEP) and body position were analysed. SETTING: Research animal laboratory. MATERIALS: Seven anaesthetised, paralysed and ventilated healthy pigs of 21 kg. MEASUREMENTS: P/V curves up to a pressure of about 40 cmH(2)O were recorded with a computer-controlled ventilator. P(st)/V curves were obtained with the static occlusion method and P(dyn)/V curves during an insufflation at a low, constant flow rate. RESULTS: P(dyn)/V recording showed a complex pattern. During the insufflation compliance increased, fell, increased and fell again. A 2nd P(dyn)/V recording immediately following the 1st one was displaced towards higher volumes and showed only one maximum of compliance. The difference between the two curves reflected: (1) lung collapse during a period of 5 min of ventilation at zero end-expiratory pressure (ZEEP) following a recruitment manoeuvre, (2) recruitment during the measurement of the 1st P(dyn)/V curve. These observations were similar in the supine and in the left lateral position. After ventilation at PEEP, 4 cmH(2)O, the signs of collapse and recruitment were reduced. It was confirmed that PEEP offers a partial protection against collapse. P(st)/V curves showed higher volumes and higher compliance values compared to P(dyn)/V curves. This reflects the influence of viscoelastance on P(dyn)/V curves. CONCLUSION: The study demonstrates a particularly strong tendency to lung collapse in pigs.

Iloprost attenuates trauma-related pulmonary sequestration of leucocytes and platelets.

The purpose of this study was to investigate the effects of iloprost, a synthetic prostacyclin analogue, on the pulmonary cellular trapping after a standardized soft tissue trauma. In two groups 1 and 2 iloprost was given in doses of 100 ng/kg/min commencing 30 and 20 min respectively prior to trauma and ceasing 10 min after trauma. 111Indium-oxine was used to label neutrophils in 6 animals from each group. Platelets were labelled in 6 and 7 animals respectively. A third group of 11 pigs served as a control and did not receive iloprost. The pulmonary sequestration of platelets and neutrophils was studied dynamically with a gamma camera and directly after trauma was significantly less in group 1 when compared to the control group. A rise in pulmonary vascular resistance and pulmonary arterial pressure was seen in the control group immediately after trauma but this was not evident in the iloprost groups. PaO2 decreased significantly in group 1 and 2 during the iloprost infusion. The results indicate that iloprost attenuates the pulmonary cellular sequestration and changes in central hemodynamics during trauma in this model.

Significance of serum S100 release after coronary artery bypass grafting.

BACKGROUND: S100 protein has been suggested to be a serum marker for cerebral complications after cardiac operation and extracorporeal circulation. The aim of this study was to characterize the S100 release pattern after extracorporeal circulation in 515 consecutive patients undergoing coronary artery bypass grafting. METHODS: Clinical variables and outcome were prospectively registered. The cerebral outcome was determined by clinical examination. S100 was measured at the end of extracorporeal circulation, and after 5, 15, and 48 hours. RESULTS: After operation, 13 patients had stroke, 12 had delayed awakening, and 17 had encephalopathy. Early S100 release, immediately after extracorporeal circulation, was associated with age and perfusion time, but not with cerebral outcome. However, S100 release after 5 to 48 hours was associated with cerebral complications and risk factors for such outcome. Patients with stroke had higher S100 levels after 15 to 48 hours. A subset of patients with renal failure had overall higher S100 levels at 5 hours. CONCLUSIONS: Early and late S100 release indicate different mechanisms for release and emphasizes the potential power of this new biochemical marker for cerebral damage.

S100B as a predictor of size and outcome of stroke after cardiac surgery.

BACKGROUND: Stroke after cardiac surgery is a clinical problem with often fatal or disabling outcome. To assess severity and probable outcome in affected patients only from clinical and radiological examinations is difficult. The glial-derived protein S100B has been suggested to be a marker of cerebral ischemia, and increased blood concentrations of S100B have been shown to correlate with size of lesion and prognosis after stroke. We studied the validity of S100B as a predictor of size of brain lesion and median term outcome in a consecutive group of patients suffering from stroke after cardiac surgery. METHODS: During a period of 17 months, 20 patients with clinical signs of postoperative stroke were investigated with S100B measurement, sampled at 5, 15 and 48 hours after surgery. All patients were examined with computed tomography or magnetic resonance imaging to confirm the diagnosis, and the size of cerebral infarction was estimated from the radiological examinations. The patients were followed up for survival 24 to 39 months after surgery. RESULTS: S100B concentration in blood 48 hours after surgery correlated with the size of infarcted brain tissue (r = 0.68, p < 0.001). Nine patients had S100B levels exceeding 0.5 microg/L and a 2-year mortality of 78%, whereas the 11 patients with S100B below 0.5 microg/L had a mortality of 18%. CONCLUSIONS: Increased S100B in patients with a stroke following cardiac surgery correlate with the size of infarcted brain tissue. High S100B levels 48 hours after surgery have a negative predictive value for median term survival.

Neuron-specific enolase increases in plasma during and immediately after extracorporeal circulation.

BACKGROUND: Minor cerebral complications are common after cardiac surgery. Several biochemical markers for brain injury are under research; one of these is neuron-specific enolase (NSE). The purpose of this study was to investigate the release of this enzyme into the blood during and immediately after extracorporeal circulation and to evaluate the effect of hemolysis on this release. METHODS: Sixteen patients scheduled for elective heart surgery were included in the study. Blood samples for analysis of NSE and free hemoglobin in plasma were drawn before, during, and up to 48 hours after the end of extracorporeal circulation. The release of NSE from erythrocytes and its correlation to the release of free hemoglobin was studied by serial dilution and hemolysis in vitro. RESULTS: The peri- and postoperative course was uneventful in all patients. Extracorporeal circulation initiated a release of NSE that reached a maximum 6 hours after the end of perfusion. Thereafter, the levels declined with an estimated t1/2 of 30 hours. The concentration of free hemoglobin increased during the perfusion, with maximum levels at the end of perfusion, after which they fell rapidly to normal values. The in vitro study showed a strong linearity between the release of NSE and free hemoglobin after induced hemolysis. CONCLUSIONS: The increased levels of enolase at the end of cardiopulmonary bypass can, to a major part, be explained by the release from hemolysed erythrocytes. The value of NSE as a marker for brain injury in these situations is therefore doubtful.

S100beta after coronary artery surgery: release pattern, source of contamination, and relation to neuropsychological outcome.

BACKGROUND: S100beta has been suggested as a marker of brain damage after cardiac operation. The aim of this study was to characterize the early S100beta release in detail and relate it to neuropsychological outcome. METHODS: Three groups of patients were investigated. All patients underwent coronary artery bypass surgery (CABG) with extracorporeal circulation. In group A, 110 patients had sampling of S100beta for the first 10 postoperative hours and also underwent neuropsychological testing. In group B, 14 patients were examined for the effect of autotransfusion on S100beta levels. Eight patients in group C had their intraoperative bleeding processed with a cell-saving device. RESULTS: Group A had a heterogeneous release pattern with several rapid elevations in S100beta concentration. In group B, high concentrations of S100beta were found in the autotransfusion blood (range 0.2 to 210 microg/L) with a concurrent elevation of serum S100beta levels after transfusion of shed blood. In group C, high levels of S100beta were found in the blood from the surgical field (12.0+/-6.0 microg/L) and decreased (1.1+/-0.64 microg/L) after wash. Group C had significantly lower S100beta values at the end of cardiopulmonary bypass compared to group A (0.53+/-0.35 microg/L versus 2.40+/-1.5 microg/L). S100beta values were corrected for extracerebral contamination with a kinetic model. With this correction, an association was found between adverse neuropsychological outcome and S100beta release in group A (r = 0.39, p < 0.02). CONCLUSIONS: A significant amount of S100beta is found both in the blood from the surgical field and in the shed mediastinal blood postoperatively. Infusion of this blood will result in infusion of S100beta into the blood and interfere in the interpretation of early systemic S100beta values.

Prevention of posttraumatic pulmonary platelet trapping by portacaval transposition.

Significant soft-tissue trauma induces platelet activation, aggregation, and sequestration in the lungs. This pulmonary trapping is due either to the size of the platelet aggregates or to changes in the pulmonary microvasculature. To evaluate which one of these mechanisms is responsible for the trapping, we performed portacaval transposition in one group of pigs, making the liver the first receiving capillary bed for blood from the trauma sites in the lower extremities. One week after the operation, the platelets were labeled with indium oxine and reinfused, and the operated animals and a group of six control animals were subjected to standardized soft-tissue trauma to the lower extremities. Sequestration of platelets in the lungs and in the liver was registered dynamically before and for 90 minutes after the trauma. Soft-tissue trauma induced platelet sequestration in the liver in the operated group (p less than 0.01) and in the lungs in the control group (p less than 0.01). Trapping was paralleled by a decrease in the number of circulating platelets. This study has indicated that posttraumatic pulmonary platelet trapping is caused by platelet activation at the trauma sites and not by changes in the pulmonary microvasculature.

Early posttraumatic pulmonary platelet trapping and its potentiation by oral pretreatment with alcohol.

Soft tissue trauma is associated with platelet aggregation and sequestration in the lungs. This is believed to be an early step in the later development of adult respiratory distress syndrome. In the present experiment using a new method for in vivo dynamic studies of platelet sequestration, we wanted to evaluate the effect of soft tissue trauma on pulmonary platelet trapping in pigs and the influence of acute alcohol intoxication. The results show that significant pulmonary platelet trapping is registered within minutes of trauma and that alcohol significantly increases platelet sequestration in the lungs. This indicates an increased risk for posttraumatic pulmonary problems in alcohol-intoxicated trauma victims.

Clinical experience with a novel endotoxin adsorbtion device in patients undergoing cardiac surgery.

Endotoxaemia is thought to occur in cardiac surgery using extracorporeal circulation (ECC) and a positive correlation has been proposed between the magnitude of endotoxaemia and risk for postoperative complications. We studied the effects of a new endotoxin adsorber device (Alteco LPS adsorber) in patients undergoing cardiac surgery with ECC, with special reference to safety and ease of use. Fifteen patients undergoing coronary artery bypass and/or valvular surgery were studied. In 9 patients, the LPS Adsorber was included in the bypass circuit between the arterial filter and the venous reservoir. Flow through the adsorber was started when the aorta was clamped and stopped at the end of perfusion. Flow rate was kept at 150 ml/min. Six patients served as controls with no adsorber in the circuit. Samples were taken for analysis of endotoxin, TNFalpha, IL-1beta and IL-6 as well as complement factors C3, C4 and C1q. Whole blood coagulation status was evaluated using thromboelastograpy (TEG) and platelet count. No adverse events were encountered when the adsorber was used in the circuit. Blood flow through the device was easily monitored and kept at the desired level. Platelet count decreased in both groups during surgery. TEG data revealed a decrease in whole blood clot strength in the control group while it was preserved in the adsorber group. Endotoxin was detected in only 2 patients and IL-1beta in 4 patients. IL-6 decreased in both groups whereas no change in TNF concentrations was found. C3 fell in both groups, but no changes wer found in C4 and C1q. The Alteco LPS adsorber can be used safely and is easy to handle in the bypass circuit. No complications related to the use of the adsorber were noted. The intended effects of the adsorber, i.e. removal of endotoxin from the blood stream could not be evaluated in this study, presumably due to the small number of patients and the relatively short perfusion times.

Effect of epidural analgesia on immediate posttraumatic cardiovascular hemodynamics and pulmonary platelet trapping.

Immediate reactions to different types of trauma have been the object of several studies recently. Thus, it has been shown that pulmonary platelet trapping (PPT) occurs within minutes after both septic and traumatic shock following soft tissue trauma. To study whether block of the nervous supply to the traumatized tissue had any effect on PPT, 40 mg of mepivacaine was injected through an epidural catheter inserted between the second and third lumbar vertebrae in pigs. After a period of stabilization the animals were subjected to a standardized soft tissue trauma to the hind limbs. A group of animals without an epidural catheter served as control. The trauma induced a profound decrease in cardiac output and mean arterial pressure. Pulmonary platelet trapping was recorded dynamically by labelling platelets with radioactive indium. Trapping of platelets in the lungs occurred immediately after the trauma, and there was no difference in animals pretreated with epidural block compared with the control animals. Our findings indicate that the trapping of platelets after soft tissue trauma is triggered at the trauma site and not affected by a block of the nervous supply to the trauma sites, including the peripheral sympathetic outflow.

Static v. dynamic tests in the in vitro diagnosis of malignant hyperthermia susceptibility.

In vitro contracture tests, in which muscle specimens are exposed to halothane or caffeine are, at present, the only generally accepted screening methods for the diagnosis of susceptibility to malignant hyperthermia (MHS). Static tests (performed with the muscle held at constant length) are used more commonly although, in addition, some MH investigation units use dynamic tests, in which the length of the specimen is varied. We have performed dynamic and static tests in parallel on muscle from 112 patients. The dynamic halothane test was more sensitive in discriminating between MHS and MH negative (MHN) individuals than the static halothane test. However, the dynamic caffeine test was less sensitive at discriminating between MHS and MHN individuals, and nothing is to be gained by including it in the investigation.

Central hemodynamics and pulmonary ventilation after trauma: effect of portacaval transposition.

Immediate reaction to traumatic shock involves, among other factors, trapping of platelets in the lungs. It has previously been shown that this trapping is associated with an increase in pulmonary vascular resistance (PVR). To elucidate whether this increase in PVR was due to cellular sequestration or other factors, we performed a portacaval transposition in a group of pigs (n = 9), making the liver the first receiving capillary bed for blood from the lower extremities. One week later, these animals and a control group (n = 6) were subjected to a standardized soft tissue trauma to the hind limbs. Following trauma, there was an immediate increase in PVR in the control group but not in the operated animals. This increase in PVR was accompanied by a fall in alveolar ventilation that was significantly lower in the control group than in the operated animals. There were no differences in blood gases, probably because of high FiO2 during the experiment. Our findings indicate that the early response in pulmonary circulation following trauma is due to cellular sequestration from the trauma sites.

Different effects of bleeding and soft-tissue trauma on pulmonary platelet trapping in pigs.

Immediate reactions to different types of trauma have been the object of several studies recently. It has been shown that pulmonary platelet trapping (PPT) occurs within minutes after both septic shock and soft-tissue trauma. The purpose of this study was to investigate whether hypovolemia induced by hypoperfusion might trigger platelet trapping in the lungs in the same way as soft-tissue trauma. Platelets labelled with indium-oxine were reinfused in anesthetized and mechanically ventilated pigs 4 hours before either induction of standardized hypovolemia caused by bleeding to the amount of 20% of the estimated blood volume (n = 6) or a standardized soft-tissue trauma to the hind limbs (n = 7). Platelet sequestration in the lungs was recorded dynamically by means of scintigraphy for 15 minutes before and 90 min after the start of the trauma and bleeding episodes. Central hemodynamics were recorded using a Swan-Ganz catheter. Soft-tissue trauma induced a marked PPT; in the animals subjected to bleeding alone there was no such effect despite a hemodynamic deterioration of greater magnitude than in the trauma group. The PPT was accompanied by a reduction in the number of platelets and leukocytes in peripheral blood. Our results indicate that immediate trapping of platelets in the lungs after trauma occurs as a response to factors other than those related to simple hypovolemic hypoperfusion.

Anaesthesia for resection of tumours in the trachea and central bronchi using the Nd-YAG-laser technique.

The use of lasers in upper airway surgery is now common practice. The introduction of the Nd-YAG laser technique makes it possible to perform endoscopic resection of tumours located in the trachea and central bronchi. Usually these patients require general anaesthesia. Our experience in 13 patients using total intravenous anaesthesia and jet ventilation with air is reported. Oxygen saturation was maintained at a higher level than when the patients were breathing 100% oxygen before anaesthesia. Occasional reductions in saturation were due to airway obstruction and were easily corrected by a short interruption of the procedure. All patients tolerated the anaesthesia and surgery well. No complications related to the anaesthetic method or the use of the Nd-YAG-laser occurred. A review of the possible hazards in these procedures is given together with advice on safety precautions needed.

Serum antibodies to pneumolysin in patients with pneumonia.

Serum antibodies to purified pneumolysin were determined by enzyme-linked immunosorbent assay (ELISA) in paired samples from 406 adult patients with community-acquired pneumonia and in samples from 184 healthy controls. A high sensitivity (83%) was obtained in patients with blood culture-confirmed pneumococcal pneumonia. In patients with a tentative pneumococcal diagnosis based on culture of samples from the sputum or the nasopharynx, 45% were positive by ELISA. The difference likely reflected the different relevance of cultural findings for the diagnosis of pneumococcal pneumonia. A significant rise in ELISA titer was found in 17% of the patients. When the diagnosis was also based on high titers, 25% were positive. Pneumococcal pneumonia diagnosed by the pneumolysin ELISA was significantly more common in the patients with a more severe disease and who required hospitalization (21 versus 5% for outpatients). Younger patients were more often positive for pneumococci as determined by high titers, while older patients showed titer rises. Mixed infections with other infectious agents were not uncommon. The finding of low titers in acute-phase samples from positive patients and in the youngest and oldest age groups of healthy controls were unexpected, indicating that further studies on the role of pneumolysin in pneumococcal disease are warranted.

Increased pulmonary platelet sequestration due to infusion of cold saline during extracorporeal circulation.

We have previously documented that neutrophils (polymorphonuclear leukocytes) aggregate in the lungs 10-15 min after the start of dialysis. The aim of the present study was to investigate the corresponding platelet reaction and evaluate the effect of prewarmed priming solution on this reaction. The animals were divided into two groups, each consisting of 6 pigs. In group 1 the priming solution was prewarmed to 36-38 degrees C whereas it was maintained at room temperature in group 2. Platelets were selectively labelled with 111In-oxine. The activity over the lung was followed dynamically with a gamma camera and already after 2 min a significant difference in platelet sequestration showed between the groups. A significant increase in pulmonary vascular resistance was noted in group 2, but not in group 1. In conclusion, platelet aggregation occurs early on during dialysis in this model. The results also indicate that prewarming the priming solution attenuates the pulmonary platelet sequestration and also seems to decrease the changes in central hemodynamics.