Gunnar Malmkvist

The Appearance of S-100 Protein in Serum During and Immediately After Cardiopulmonary Bypass Surgery: A Possible Marker for Cerebral Injury

OBJECTIVE To investigate the appearance and elimination of brain-specific S-100 protein in serum during and immediately after cardiopulmonary bypass. DESIGN Prospective study. PARTICIPANTS Twenty-nine patients undergoing elective cardiac surgery. INTERVENTIONS Twenty-seven patients were operated on for coronary artery disease; two patients had valve replacement. Serial measurements of S-100 in arterial blood during and up to 48 hours after cardiopulmonary bypass were made. MEASUREMENTS AND MAIN RESULTS The perioperative and postoperative course was uneventful in 25 patients, with no clinical signs of neurologic complications. S-100 was not detected before extracorporeal circulation was started. Detectable concentrations (detection limit, 0.2 microgram/L) appeared in serum after 10 minutes of perfusion and reached maximum levels, 2.43 +/- 0.3 micrograms/L, at the end of bypass. The levels then declined with elimination t1/2 of 2.2 hours. Only two patients had detectable concentrations of S-100 48 hours after the end of bypass. In four patients who developed clinical signs of cerebral injury, levels of S-100 were significantly higher at the end of bypass and 24 hours after the end of bypass. CONCLUSIONS Cardiopulmonary bypass initiates a release of brain-specific S-100 to the systemic circulation. The release and elimination of S-100 seem to follow a reproducible pattern in patients with no signs of cerebral injury. In patients who developed cerebral injury, the concentrations of S-100 in blood were increased, thus suggesting that S-100 may be a usable marker for cerebral injury after extracorporeal circulation.

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.

Wash-in kinetics for sevoflurane using a disposable delivery system (AnaConDa®) in cardiac surgery patients

BACKGROUND The use of volatile anaesthetics has increased in situations where conventional anaesthetic machines are inadequate or unavailable, for example, cardiac surgery and intensive care. The disposable anaesthetic conserving device, AnaConDa, allows vaporization of liquid volatile anaesthetics from a syringe pump and rebreathing of exhaled anaesthetic. Clinical use requires understanding of device-specific anaesthetic agent kinetics, which are not fully known. We compared the wash-in kinetics for sevoflurane administered by a conventional vaporizer in a non-rebreathing system and the AnaConDa and evaluated if a standard anaesthesia gas monitor gave accurate readings while using the AnaConDa. METHODS Cardiac surgery patients were randomized to maintenance of anaesthesia with sevoflurane either via a vaporizer or via the AnaConDa (n=8 in each group). Sevoflurane in arterial blood and airway gas was measured with gas chromatography and standard gas monitoring. RESULTS The initial increase in arterial sevoflurane tension was greater with the vaporizer than with the AnaConDa, but the time to reach 80% of maximum sevoflurane tension was close to 8 min in both groups. End-tidal sevoflurane tension mirrored arterial tension in both groups, whereas measured inspired tension was lower than expired and arterial tensions with the use of the AnaConDa. CONCLUSIONS The wash-in kinetics for sevoflurane delivered by the AnaConDa are similar to a vaporizer. End-tidal sevoflurane tension accurately reflects arterial tension whereas inspired tension may be underestimated using an AnaConDa.

Maintenance of Oxygenation during One-lung Ventilation: Effect of Intermittent Reinflation of the Collapsed Lung with Oxygen

The aim of this study was to evaluate the effect on oxygenation of intermittent inflation with oxygen of the collapsed lung during one-lung ventilation (OLV). Sixteen patients were studied during pulmonary surgery. Balanced anesthesia with nitrous oxide and an inspired oxygen fraction of 0.5 was used. The control group (N=8) had a median PaO2 of 19.2 (range 12.2--30.2) kPa before OLV, and 10.2 (8.2--16.0) kPa after 9 minutes of OLV without further reduction in PaO2 for another 10 minutes. In the treatment (inflation) group, the collapsed lung was manually inflated with 2 liters of oxygen and was then immediately allowed to collapse again. This procedure was repeated every 5 minutes during OLV. PaO2 increased more than 4 kPa following each inflation in seven patients. In the eighth, PaO2 remained high throughout OLV. Although PaO2 decreased between inflations, it never reached the level observed in controls during 19 minutes of OLV.

Carbon dioxide rebreathing with the anaesthetic conserving device, AnaConDa®

BACKGROUND The anaesthetic conserving device (ACD) AnaConDa(®) was developed to allow the reduced use of inhaled agents by conserving exhaled agent and allowing rebreathing. Elevated has been observed in patients when using this ACD, despite tidal volume compensation for the larger apparatus dead space. The aim of the present study was to determine whether CO(2), like inhaled anaesthetics, adsorbs to the ACD during expiration and returns to a test lung during the following inspiration. METHODS The ACD was attached to an experimental test lung. Apparent dead space by the single-breath test for CO(2) and the amount of CO(2) adsorbed to the carbon filter of the ACD was measured with infrared spectrometry. RESULTS Apparent dead space was 230 ml larger using the ACD compared with a conventional heat and moisture exchanger (internal volumes 100 and 50 ml, respectively). Varying CO(2) flux to the test lung (85-375 ml min(-1)) did not change the measured dead space nor did varying respiratory rate (12-24 bpm). The ACD contained 3.3 times more CO(2) than the predicted amount present in its internal volume of 100 ml. CONCLUSIONS Our measurements show a CO(2) reservoir effect of 180 ml in excess of the ACD internal volume. This is due to adsorption of CO(2) in the ACD during expiration and return of CO(2) during the following inspiration.

Anaesthetic conserving device AnaConDa: dead space effect and significance for lung protective ventilation.

BACKGROUND The anaesthetic conserving device AnaConDa (ACD) reflects exhaled anaesthetic agents thereby facilitating the use of inhaled anaesthetic agents outside operating theatres. Expired CO₂ is, however, also reflected causing a dead space effect in excess of the ACD internal volume. CO₂ reflection from the ACD is attenuated by humidity. This study tests the hypothesis that sevoflurane further attenuates reflection of CO₂. An analysis of clinical implications of our findings was performed. METHODS Twelve postoperative patients received mechanical ventilation using a conventional heat and moisture exchanger (HME, internal volume 50 ml) and an ACD (100 ml), the latter with or without administration of sevoflurane. The ACD was also studied with a test lung at high sevoflurane concentrations. Reflection of CO₂ and dead space effects were evaluated with the single-breath test for CO2. RESULTS Sevoflurane reduced but did not abolish CO₂ reflection. In patients, the mean dead space effect with 0.8% sevoflurane was 88 ml larger using the ACD compared with the HME (P<0.001), of which 38 ml was due to CO₂ reflection. Our calculations show that with the use of the ACD, normocapnia cannot be achieved with tidal volume <6 ml kg(-1) even when respiratory rate is increased. CONCLUSIONS An ACD causes a dead space effect larger than its internal volume due to reflection of CO₂, which is attenuated but not abolished by sevoflurane administration. CO₂ reflection from the ACD limits its use with low tidal volume ventilation, such as with lung protection ventilation strategies. CLINICAL TRIAL REGISTRATION Clinical Trials NCT01699802.

Apparent dead space with the anesthetic conserving device, AnaConDa®: a clinical and laboratory investigation.

BACKGROUND: The anesthetic conserving device (ACD) reduces consumption of volatile anesthetic drug by a conserving medium adsorbing exhaled drug during expiration and releasing it during inspiration. Elevated arterial CO2 tension (PaCO2) has been observed in patients using the ACD, despite tidal volume increase to compensate for larger apparatus dead space. In a test lung using room temperature dry gas, this was shown to be due to adsorption of CO2 in the ACD during expiration and release of CO2 during the following inspiration. The effect in the test lung was higher than in patients. We tested the hypothesis that a lesser dead space effect in patients is due to higher temperature and/or moisture attenuating rebreathing of CO2. METHODS: The lungs of 6 postoperative cardiac surgery patients were ventilated using a conventional heat and moisture exchanger (HME) or an ACD. The ACD was studied with a test lung at varying temperatures and moistures. Infrared spectrometry was used to measure apparent dead space by the single-breath test for CO2 as well as rebreathing of CO2. RESULTS: In patients, the median apparent dead space was 136 mL (95% confidence interval [CI,] 120–167) larger using the ACD compared with an HME (after correction for difference in internal volume 100 and 50 mL, respectively). Median rebreathing of CO2 using the ACD was 53% (range 48–58) of exhaled CO2 compared with 29% (range 27–32) with an HME. The median difference in CO2 rebreathing was 23% (95% CI, 18–27). In the test lung apparent dead space using ACD was unaffected by body temperature but decreased from 360 to 260 mL when moisture was added. This decreased rebreathing of CO2 from 62% to 48%. CONCLUSIONS: The use of an ACD increases apparent dead space to a greater extent than can be explained by its internal volume. This is caused by adsorption of CO2 in the ACD during expiration and release of CO2 during inspiration. Rebreathing of CO2 was attenuated by moisture. The dead space effect of the ACD could be clinically relevant in acute respiratory distress syndrome and other diseases associated with ventilation difficulties, but investigations with larger sample sizes would be needed to determine the clinical importance.

A randomized study of coronary artery bypass surgery performed with the Resting Heart™ System utilizing a low vs a standard dosage of heparin

OBJECTIVES Allogeneic blood transfusion and reoperation for postoperative bleeding after the coronary artery bypass grafting have a negative impact on the patient outcome. This study aimed at evaluating the effects of reduced doses of heparin and protamine on the patient outcome, using a heparin-coated mini-cardiopulmonary bypass (CPB) system. METHODS Sixty patients undergoing elective first-time CPB were prospectively randomized either to have a reduced systemic heparinization [activated clotting time (ACT) = 250 s] or to a control group perfused with a full heparin dose (ACT = 420 s). Blood transfusions, ventilation time, early postoperative bleeding, ICU stay, reoperations for bleeding, postoperative cognitive status and the level of mobilization were registered. RESULTS Twenty-nine patients were randomized to the control group, 27 patients to the low-dose group and 4 patients were excluded because of protocol violations. Four patients in the control group received a total of 10 units of packed red blood cells, and in the low-dose group, no transfusions were given, P = 0.046. No patient was reoperated because of bleeding. The ICU stay was significantly shorter in the low-dose group (8.4 vs 13.7 h, P = 0.020), less dependent on oxygen on the first postoperative day (78 vs 97%, P = 0.034), better mobilized (89 vs 59%, P = 0.006) and had less pain (visual analogue scale 2.0 vs 3.5, P = 0.019) compared with the control group. CONCLUSIONS The use of a mini-CPB system combined with a low dose of heparin reduced the need for blood transfusions and may facilitate the faster mobilization of the patients.

An appropriate inspiratory flow pattern can enhance CO2 exchange, facilitating protective ventilation of healthy lungs

BACKGROUND In acute lung injury, CO2 exchange is enhanced by prolonging the volume-weighted mean time for fresh gas to mix with resident alveolar gas, denoted mean distribution time (MDT), and by increasing the flow rate immediately before inspiratory flow interruption, end-inspiratory flow (EIF). The objective was to study these effects in human subjects without lung disease and to analyse the results with respect to lung-protective ventilation of healthy lungs. METHODS During preparation for intracranial surgery, the lungs of eight subjects were ventilated with a computer-controlled ventilator, allowing breath-by-breath modification of the inspiratory flow pattern. The durations of inspiration (TI) and postinspiratory pause (TP) were modified, as was the profile of the inspiratory flow wave (i.e. constant, increasing, or decreasing). The single-breath test for CO2 was used to quantify airway dead space (VDaw) and CO2 exchange. RESULTS A long MDT and a high EIF augment CO2 elimination by reducing VDaw and promoting mixing of tidal gas with resident alveolar gas. A heat and moisture exchanger had no other effect than enlarging VDaw. A change of TI from 33 to 15% and of TP from 10 to 28%, leaving the time for expiration unchanged, would augment tidal elimination of CO2 by 14%, allowing a 10% lower tidal volume. CONCLUSIONS In anaesthetized human subjects without lung disease, CO2 exchange is enhanced by a long MDT and a high EIF. A short TI and a long TP allow significant reduction of tidal volume when lung-protective ventilation is required. CLINICAL TRIAL REGISTRATION NCT01686984.

Modified inspiratory flow pattern - a tool for lung protective ventilation

Lung protective ventilation, LPV, is recommended for ever wider patient populations, even those without primary lung disease. Low tidal volume ventilation is a first-hand remedy for LPV that is facilitated by dead space reduction. Inspiratory flow pattern affects gas exchange. In ARDS patients, it was recently shown that a long period during which inspired tidal gas is in contact with resident alveolar gas, mean distribution time, MDT, as well as a high end inspiratory flow, EIF, immediately before interruption of inspiration augment exchange of C02 by reduction of airway and alveolar dead space.