Göran Settergren

High Serum S100B Levels for Trauma Patients without Head Injuries

OBJECTIVE Studies of patients with head trauma have demonstrated a correlation between a serum marker of brain tissue damage, namely S100B, and neuroradiological findings. It was recently demonstrated that the increases in serum S100B levels after heart surgery have extracerebral origins, probably surgically traumatized fat, muscle, and bone marrow. The current study examined multitrauma patients without head trauma, to determine whether soft-tissue and bone damage might confound the interpretation of elevated serum S100B concentrations for patients after head trauma. METHODS A commercial assay was used to determine serum S100B concentrations for a normal population (n = 459) and multitrauma patients without head injury (n = 17). Concentrations of the two subtypes of S100B (S100A1B and S100BB) were determined using separate noncommercial assays. RESULTS The mean serum S100B concentration for a normal healthy population was 0.032 microg/L (median, 0.010 microg/L; standard deviation, 0.040 microg/L). The upper 97.5% and 95% reference limits were 0.13 and 0.10 microg/L, respectively. No major age or sex differences were observed. Among trauma patients, serum S100B levels were highest after bone fractures (range, 2-10 microg/L) and thoracic contusions without fractures (range, 0.5-4 microg/L). Burns (range, 0.8-5 microg/L) and minor bruises also produced increased S100B levels. S100A1B and S100BB were detected in all samples. CONCLUSION Trauma, even in the absence of head trauma, results in high serum concentrations of S100B. Interpretation of elevated S100B concentrations immediately after multitrauma may be difficult because of extracerebral contributions. S100B may have a negative predictive value to exclude brain tissue damage after trauma. Similarly, nonacute S100B measurements may be of greater prognostic value than acute measurements.

Increase in serum S100A1-B and S100BB during cardiac surgery arises from extracerebral sources

BACKGROUND Elevated levels of serum S100B after coronary artery bypass grafting may arise from extracerebral contamination. Serum S100B content was analyzed in several tissues, and the two dimers S100A1-B and S100BB were analyzed separately in blood. METHODS Serum, shed blood, marrow, fat, and muscle were studied in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass using suction either to the cardiotomy reservoir (group 1, n = 10) or to a cell-saving device (group 2, n = 10), or operated on off-pump (group 3, n = 10). RESULTS Serum S100B was sixfold higher in group 1 than in groups 2 and 3, which were identical. The same ratio between S100A1-B and S100BB was found in all groups. When compared with serum, S100B was 10(2) to 10(4) times higher in marrow, fat, muscle tissue, and shed blood. CONCLUSIONS Separate analysis of S100A1-B and S100BB did not distinguish between S100B of cerebral and extracerebral origin. The concept that S100B only originates in astroglial and Schwann cells is wrong. Fat, muscle, and marrow in mediastinal blood contain high levels of S100B. Cardiopulmonary bypass caused no increase in S100B.

The effect of cardiotomy suction on the brain injury marker S100β after cardiopulmonary bypass

BACKGROUND An increase of S100beta in serum during cardiopulmonary bypass (CPB) has been interpreted as a sign of brain injury. Cardiotomy suction may cause fat embolization, and its role in the S100beta increase was examined. METHODS Twenty coronary artery operation patients were randomly assigned to two groups, 10 with suction during CPB to cardiotomy reservoir (CR), 10 to cell saving device (CS). S100beta was measured (immunoassay) in blood from the patients and from cell saving device after processing. In 7 additional patients S100beta was measured in the cell saving device before processing and directly from the wound at sternotomy. RESULTS Before anesthesia, serum S100beta was 0.03+/-0.06 microg/L. At the end of CPB it was 2.47+/-1.31 microg/L and 0.44+/-0.27 microg/L (CR vs CS; p < 0.001). S100beta was 33+/-12 microg/L in CS reservoir and 42+/-18 microg/L in blood from the wound. CONCLUSIONS Most serum S100beta after CPB with cardiotomy suction may be of extracerebral origin. S100beta after CPB with cell saving device was the same as after off-pump operation. The interpretation that an increase in S100beta during CPB in patients reflects cerebral injury must be questioned.

Increased extracellular brain water after coronary artery bypass grafting is avoided by off-pump surgery

OBJECTIVE To determine if coronary artery bypass graft (CABG) surgery without cardiopulmonary bypass (CPB) avoids the brain swelling known to occur after CPB, to quantify these brain water compartment changes, and to identify the water shifts as due to intracellular or extracellular water. DESIGN Prospective, controlled, and blinded. SETTING Cardiac surgical unit in a university teaching hospital. SUBJECTS Patients scheduled for CABG who were assigned to conventional (n = 10) or off-pump (n = 7) surgery according to their coronary anatomy. INTERVENTIONS Magnetic resonance imaging (MRI) examinations were performed 1 day before surgery and 1 hour and 1 week after CABG surgery. MAIN OUTCOME MEASURES Extracellular and intracellular water homeostasis was described quantitatively by calculating the averaged apparent diffusion coefficient of brain water using diffusion-weighted MRI. Blinded visual ordering of the images from the three examinations was performed according to brain size using conventional MRI. RESULTS The average diffusion coefficient of brain water increased 4.7%+/-1.5% immediately after CABG with CPB and normalized after 1 week but did not change after CABG without CPB. No focal ischemic changes were seen in either group, and no gross neurologic deficits were observed. Visual analysis showed consistent brain swelling after CPB and variable changes in those operated without CPB. CONCLUSION Changes consistent with increased extracellular brain water seen after CABG with CPB were not observed in patients undergoing CABG without CPB. The clinical significance of brain water changes and increased brain water content after surgery with CPB remains undefined.

Biochemical markers of cerebrospinal ischemia after repair of aneurysms of the descending and thoracoabdominal aorta.

OBJECTIVE To investigate the clinical potential of several markers of spinal cord ischemia in cerebrospinal fluid (CSF) and serum during aneurysm repair of the descending thoracic or thoracoabdominal aorta. DESIGN Observational study of consecutive patients. Nonblinded, nonrandomized. SETTING University hospital thoracic surgical unit. PARTICIPANTS Eleven consecutive elective patients. INTERVENTIONS Distal extracorporeal circulation and maintenance of CSF pressure <10 mmHg until intrathecal catheter removal. MEASUREMENTS AND MAIN RESULTS CSF and serum levels of S100B (and its isoforms S100A1B and S100BB), neuronal-specific enolase (NSE), and the CSF levels of glial fibrillary acidic protein (GFAp) and lactate were determined. Two patients had postoperative neurologic deficit. One with a stroke showed a 540-fold increased GFAp, a 6-fold NSE, and S100B increase in CSF. One with paraplegia had a 270-fold increase in GFAp, a 2-fold increase in NSE, and 5-fold increased S100B in CSF. One patient without deficit increased GFAp 10-fold, NSE 4-fold, and S100B 23-fold in CSF. CSF lactate increased >50% in 6 of 9 patients without neurologic deficit. Serum S100B increased within 1 hour of surgery in all patients without any concomitant increase in CSF. S100A1B was about 70% of total S100B in both serum and CSF in patients with or without neurologic defects. S100B in CSF increased 3-fold in 3 of 9 asymptomatic patients. CONCLUSIONS In patients with neurologic deficit, GFAp in CSF showed the most pronounced increase. Biochemical markers in CSF may increase without neurologic symptoms. There is a significant increase in serum S100B from surgical trauma alone without any increase in CSF.

Protective effect of antioxidants on pulmonary endothelial function after cardiopulmonary bypass.

OBJECTIVES Pulmonary endothelium-dependent vasodilation is impaired after cardiopulmonary bypass. One explanation might be the generation of reactive oxygen species during the period without flow in the pulmonary artery. The aim of the current study was to investigate if treatment with antioxidants could improve pulmonary endothelial function after cardiopulmonary bypass and influence the blood oxidative status. DESIGN A prospective, randomized, double-blind study. SETTING The operating room, intensive care unit, and the biochemistry laboratory in University Hospitals. PARTICIPANTS Patients scheduled for cardiac surgery with cardiopulmonary bypass. INTERVENTIONS Treatment with vitamin E, vitamin C, allopurinol, and acetylcysteine (n = 12) or placebo (n = 10). MEASUREMENTS AND MAIN RESULTS The pulmonary reactivity to an infusion of acetylcholine and markers of oxidative stress in blood were measured before and after cardiopulmonary bypass. Sixteen control patients received saline instead of acetylcholine. Before surgery the pulmonary vascular resistance index decreased during infusion of acetylcholine by 24% and 21% in the treatment and placebo groups. After surgery the decrease was 20% and 8%, respectively, (p = 0.422 and p = 0.026) compared with preoperative response. Pulmonary vasodilation induced by acetylcholine was better maintained in the group treated with antioxidants (p = 0.048). In the treatment group, the blood concentrations of early intermediates of lipid peroxidation were higher, but not that of the end products. Glutathione and oxidized glutathione increased after cardiopulmonary bypass in the treatment group. CONCLUSION The better maintained endothelium-dependent vasodilation after cardiopulmonary bypass in the treatment group indicated that antioxidant therapy reduced endothelial dysfunction.

Cerebral Blood Flow and Cerebral Metabolism in Children Following Cardiac Surgery with Deep Hypothermia and Circulatory Arrest. Clinical Course and Follow-Up of Psychomotor Development

Between November 1975 and June 1977, 49 children underwent repair of complicated cardiac defects with the aid of deep hypothermia. Circulatory arrest was used in 28 cases. Nine children died (18%) due to early postoperative heart failure. A decisive cause of death in terms of important cardiovascular defects, which were either unknown or not correctable at the time of repair, was found in 6 patients. Children with complicated forms of congenital heart disease requiring an extensive repair were overrepresented among those who died. Hence, there was an excess in the duration of bypass among nonsurvivors (p less than 0.01) whereas the patients age at operation, the use of circulatory arrest and the duration of aortic occlusion had no bearing on operative mortality. Cerebral blood flow (CBF) and cerebral metabolism were studied in 9 survivors. A negative correlation (r = -0.67) was found between the duration of circulatory arrest and CBF measured directly after surgery. CBF was reduced to values below 0.2 ml . g-1 . min-1 in 3 children with long periods of circulatory arrest. The cerebral uptake of oxygen and glucose was normal both before and after surgery. Two separate interviews with the parents were performed, the first one 3-22 months and the second one about 3 years after surgery. No serious neurological symptoms or psychomotor disturbances were reported. However, in 3 children operated with circulatory arrest, difficulties in performing more delicate motor activities were noted by the parents. The findings indicate that circulatory arrest should be used with caution and total arrest periods exceeding 60 min avoided.

Incidence of sore throat and patient complaints after intraoperative transesophageal echocardiography during cardiac surgery

To evaluate the incidence of postoperative side effects and patient complaints following transesophageal echocardiography (TEE), 57 patients were interviewed by questionnaire and examined by pharyngeal inspection, preoperatively. The patients were randomized to undergo surgery with or without intraoperative TEE, and a second interview and examination were performed in 48 patients on the second postoperative day using a double-blind protocol. Twenty-four of the patients were investigated by TEE over a period of 5.4 +/- 2.3 hours and 24 had surgery without TEE. The intubation time for the two groups did not differ. There was no difference between controls and TEE patients with regard to painful swallowing evaluated by a visual analog scale. Furthermore, there was no difference between the controls and TEE patients regarding nausea or time elapsed from extubation to the first oral intake. No differences between the groups were found regarding the findings on pharyngeal inspection and no major complication attributable to the use of TEE occurred. A sore throat with painful swallowing was not a great problem for the patients in the present study; this indicates that endotracheal intubation rather than TEE caused the minor complaints. It is concluded that intraoperative TEE can be used without harmful postoperative pharyngeal side effects.

Hepatic blood flow and right ventricular function during cardiac surgery assessed by transesophageal echocardiography

OBJECTIVE To determine the effect of cardiopulmonary bypass (CPB) on hepatic blood flow (HBF) and the hepatic venous flow pattern. DESIGN Single-arm prospective study. SETTING University hospital operating room and intensive care unit. PARTICIPANTS Eight patients ranging in age from 57 to 73 years undergoing cardiac surgery. INTERVENTIONS Transesophageal echocardiography (TEE) was used to assess HBF before, during, and after CPB by pulsed-wave Doppler ultrasound recordings of hepatic venous flow velocity and two-dimensional recordings of the hepatic vein diameter. Hepatic vein oxygenation was monitored by hepatic vein catheterization, and gastric intramucosal pH (pHi) was followed by tonometry. MEASUREMENTS AND MAIN RESULTS The HBF was unchanged after the start of CPB but was reduced from the baseline value 415 (standard error of the mean 40) mL/min to 225 (25) mL/min during hypothermic CPB (p < 0.05). Cardiac index, right ventricular ejection fraction, and arterial and tonometric pH were essentially unchanged during the study period. Hepatic vein and mixed venous saturation were unchanged compared to control during CPB and were reduced at 2 and 3 hours after CPB (p < 0.01). Six of the patients had a normal predominant systolic flow pattern before surgery. In the postoperative period, seven patients showed an abnormal predominant diastolic filling pattern. CONCLUSIONS TEE represents a useful tool in assessing changes in the hepatic blood flow. The HBF was reduced during hypothermic CPB, but this was not accompanied by a reduced pHi. The changes in the venous flow pattern with a reduction in systolic flow could be explained by impaired atrial relaxation.

Effects of Intravenous Anesthesia on V̇A/V̇ DistributionA Study Performed during Ventilation with Air and with 50% Oxygen, Supine and in the Lateral Position

Distribution of ventilation and perfusion in relation to ventilation-perfusion ratio (&OV0312;A/&OV0312;) were studied in 14 patients, with a mean age of 59 yr, before elective lung surgery, in the supine position when awake, during intravenous anesthesia and mechanical ventilation with air, after increasing the fraction of inspired oxygen (FI02) to 0.5, and in the lateral position. Before anesthesia, small inert gas shunts and perfusion of low &OV0312;A/&OV0312; regions, indicating some degree of &OV0312;A/&OV0312; mismatch, were observed in several patients. After induction, FIo2 = 0.21, the major changes were a significant decrease in cardiac output and an increase in log SD for perfusion from 0.77 ± 0.45 (SD) to 1.13 ± 0.50 (SD), while the shunt remained low at 1% of cardiac output and arterial oxygen tension (PaO2) was unchanged. An increase to FIO2 = 0.5 induced only small changes with a shunt of 2.5% of cardiac output. In the lateral position, the shunt was 4.0% and increases in ventilation to high &OV0312;A/&OV0312; regions were observed. The lack of marked changes in the &OV0312;A/&OV0312; distribution after induction either could be a result of only minor alterations in the distribution of ventilation and perfusion or an effective vascular response to alveolar hypoxia (hypoxic pulmonary vasoconstriction, HPV).