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.

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.

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.

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.

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.

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.

Isocapnic high frequency jet ventilation: dead space depends on frequency, inspiratory time and entrainment.

Twelve healthy pigs were ventilated with high frequency jet ventilation via a Mallinckrodt HiLo jet tube. The expired gas was led to a conventional ventilator and CO2 analyzer which were used to measure CO2 elimination. There was no bias flow, so that the jet entrained only expired gas, i.e. rebreathing occurred. Frequency was varied between 2 and 11 Hz and the duration of inspiration, as a fraction of the ventilatory cycle (Ti/Ttot), from 5 to 20%. The minute ventilation, Vjet, delivered by the jet ventilator was adjusted to maintain a constant PaCO2. At 2 Hz and a Ti/Ttot of 5%, Vjet was of the same magnitude as ventilation during conventional intermittent positive pressure ventilation, and the total dead space fraction, VD/VT was 0.32. Both increasing frequency at a constant Ti/Ttot, and increasing Ti/Ttot at a constant frequency, increased VD/VT which was maximal (0.8) at 11 Hz and a Ti/Ttot of 20%. When entrainment was blocked, tidal jet volume had to be greatly increased. The continuous measurement of CO2 elimination was found to be useful for maintaining isocapnia when the jet ventilator setting was changed.

Effects of lung surgery and one-lung ventilation on pulmonary arterial pressure, venous admixture and immediate postoperative lung function.

We studied 17 patients, with unilateral lesions in lung or thoracic wall, during thoracotomy performed in the full lateral position. Balanced anaesthesia was used with pethidine and 50% nitrous oxide, in oxygen. The procedure included a period of one-lung ventilation (OLV). Haemodynamic and gas exchange measurements were performed before and after pleurotomy, during OLV, after re-expansion of the lung and after closure of the thoracic wall. The function of each lung was assessed separately during the first and last stages. Mean venous admixture was 9-12% before and after OLV and 31% during OLV. There was a positive correlation between venous admixture and pulmonary arterial pressure during OLV. End-tidal PCO2, carbon dioxide elimination and compliance of the operated side were reduced significantly at the end of the procedure; this is consistent with reduced blood flow and increased water content in that lung.

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 11.2-30.2) 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.

Mechanical factors do not influence blood flow distribution in atelectasis.

The contribution of mechanical factors to the vascular resistance of the atelectatic lung has been studied in vivo in the anesthetized open-chest dog. When the left lung was ventilated with an hypoxic gas mixture (while the right lung was ventilated with 100% O2), left lung blood flow decreased from 0.99 +/- 0.11 1.min-1 to 0.40 +/- 0.08 1.min-1 due to hypoxic pulmonary vasoconstriction (hypoxic stimulus PSO2 = 36.1 +/- 0.8 mmHg). When the left lung was made atelectatic, blood flow decreased to 0.65 +/- 0.11 1.min-1, consistent with a weaker hypoxic stimulus (PSO2 = 54.0 +/- 3.2 mmHg). With the addition of sodium nitroprusside infused intravenously, left lung blood flow increased to 1.05 +/- 0.14 1.min-1 during atelectasis, and to 0.61 +/- 0.09 1.min-1 during hypoxic ventilation, while flow remained at 0.94 +/- 0.18 1.min-1 during hyperoxic ventilation. When the results were plotted on pressure-flow diagrams, the hyperoxic, hypoxic, and atelectatic lung points fell on the same pressure-flow line in the presence of nitroprusside. It is concluded that hypoxic pulmonary vasoconstriction is the major (but not necessarily only) determinant of increased vascular resistance in the atelectatic lung, and that passive mechanical factors do not measurably affect blood flow distribution during open-chest atelectasis.

Intravenous PGF2 alpha infusion does not enhance hypoxic pulmonary vasoconstriction during canine one-lung hypoxia.

The effect of prostaglandin F2 alpha (PGF2 alpha) on the hypoxic pulmonary vasoconstrictor (HPV) response was studied in 12 closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2, while the left lung was either ventilated with 100% O2 ("hyperoxia") or ventilated with an hypoxic gas mixture ("hypoxia:" end-tidal PO2 approximately equal to 50.0 +/- 0.1 mmHg). Cardiac output (CO) was altered from a "normal" value of 2.89 +/- 0.26 1.min-1 to a "high" value of 3.55 +/- 0.26 1.min-1 by opening arteriovenous fistulae which allowed measurements of two points along a pressure-flow line. These four phases of left lung hypoxia or hyperoxia with normal and high cardiac output were performed in the absence of, and in the presence of, PGF2 alpha administered as a constant peripheral intravenous infusion of 1.0 microgram.kg-1.min-1. During left lung hypoxia, mean pulmonary artery pressure (PAP) increased significantly when compared to hyperoxia. With PGF2 alpha administration, mean PAP increased significantly during both hyperoxia and hypoxia. The presence or absence of PGF2 alpha had no effect on cardiac output or PaO2 during hypoxia. Relative blood flow to each lung was measured with a differential CO2 excretion (VCO2) method corrected for the Haldane effect. With both lungs hyperoxic, the percent left lung blood flow (%QL-VCO2) was 45 +/- 1%. When the left lung was exposed to hypoxia, the %QL-VCO2 decreased significantly to 29 +/- 3%. However, with the administration of PGF2 alpha, the %QL-VCO2 during left lung hypoxia did not change significantly 26 +/- 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

High-dose almitrine bismesylate inhibits hypoxic pulmonary vasoconstriction in closed-chest dogs.

The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor (HPV) response was studied in seven closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2, while the left lung was ventilated with either 100% O2 ("hyperoxia") or with an hypoxic gas mixture ("hypoxia": end-tidal PO2 = 50.1 +/- 0.1 mmHg). Cardiac output (CO) was altered from a "normal" value of 3.10 +/- 0.18 l . min-1 to a "high" value of 3.92 +/- 0.16 l . min-1 by opening arteriovenous fistulae which allowed measurements of two points along a pressure-flow line. These four phases of left lung hypoxia or hyperoxia with normal and high cardiac output were repeated in the presence and absence of almitrine. Almitrine bismesylate was administered as a constant infusion of 14.3 micrograms . kg-1 . min-1 for a mean plasma concentration of 219.5 +/- 26.4 ng . ml-1. Relative blood flow to each lung was measured with a differential CO2 excretion (VCO2) method corrected for the Haldane effect. With both lungs hyperoxic, the percent left lung blood flow (%QL-VCO2) was 44 +/- 1%. When the left lung was exposed to hypoxia, the %QL-VCO2 decreased significantly to 22 +/- 1%. However, with the administration of almitrine, the %QL-VCO2 during left lung hypoxia increased significantly to 36 +/- 2%. The arterial oxygen tension decreased significantly between hyperoxia (PaO2 = 633 +/- 6 mmHg) and hypoxia (271 +/- 31 mmHg). With the addition of almitrine, there was no change during hyperoxia; however, during hypoxia, the PaO2 decreased significantly to 124 +/- 15 mmHg. Cardiac output did not influence these findings. The pulmonary vascular conductance (G) is the slope of the pressure-flow line.(ABSTRACT TRUNCATED AT 250 WORDS)

Variations in lung volume and compliance during pulmonary surgery.

Functional residual capacity (FRC) and breath-by-breath compliance of the ventilatory system (Crs) were measured in 10 mechanically ventilated patients during anaesthesia for lung surgery (pneumonectomy, lobectomy, lung or pleural resections or exploratory thoracotomy). In eight patients not requiring pneumonectomy, FRC of the lower lung decreased by 8 +/- 9% (mean +/- 1 SD) (P less than 0.05) while that of the upper lung increased by 75 +/- 24% (P less than 0.001) when the patient was turned to the lateral position. When the pleura was opened, FRC of the lower lung decreased by a further 10 +/- 10% (P less than 0.01). One-lung ventilation (OLV), however, increased FRC of the lower lung back to the value found in the supine position before surgery. When two-lung ventilation was re-established, FRC of the lower lung was about the same as during corresponding stages before OLV. In the two patients who underwent pneumonectomy, FRC of the remaining lung was about 30% greater after OLV than at corresponding stages before surgery. In the patients not requiring pneumonectomy, Crs decreased from 29 +/- 6 ml/cm H2O to 23 +/- 6 ml/cm H2O (P less than 0.05) on the lower side when the patient was turned on his side. The corresponding figures on the upper side were 24 +/- 8 ml/cm H2O and 30 +/- 5 ml/cm H2O respectively (P less than 0.05). There was no further significant change when the pleura was opened. After surgery when the patient was turned to the supine position, Crs of the lung not operated on was almost the same as before surgery.

On-line measurement of gas-exchange during cardiac surgery.

This paper describes an on-line system for continuously monitoring expired CO2 during controlled ventilation. Signals from a Servo ventilator 900B or C and a CO2 Analyzer 930 are processed and corrected by the computer to produce a CO2 single breath test (SBT-CO2). This is the tracing of expired CO2 concentration or fraction against expired volume, from which the computer calculates the airway deadspace (VDaw). If a value for arterial PCO2 is supplied, the computer will calculate the physiological deadspace (VDphys) and the alveolar deadspace (VDalv) for each breath. The system was used to make measurements at four stages during coronary artery by-pass grafting in 13 male patients. When the sternum was opened there was a 32% increase in VDaw, and the physiological deadspace fraction therefore increased. There were reductions in VDaw after extra-corporeal circulation and again after sternal suture. By the end of surgery, the alveolar deadspace fraction had increased significantly. VDaw at this stage was smaller than pre-operatively, and so there was no net change in the physiological deadspace fraction at the end of surgery. Arterial PO2 was, however, reduced at this stage.

Gas exchange and haemodynamics during thoracotomy.

Cardiac index, systemic and pulmonary arterial pressures, carbon dioxide elimination and ventilation of each lung were studied during thoracotomy. Seventeen patients, placed in the full lateral position, were ventilated mechanically through a Carlens' tube to moderate hypocapnia. Mean cardiac index increased by 12% as the pleura was opened (P less than 0.05), with no further change during surgery on the still ventilated upper lung. Mean arterial pressure was unchanged after opening the pleura, but decreased from 114 +/- 15 mm Hg (mean +/- 1 SD) to 104 +/- 18 mm Hg during surgery on the lung (P less than 0.01). Mean pulmonary artery pressure was unchanged. There was a significant (P less than 0.01) increase in carbon dioxide elimination from the upper lung when the pleura was opened. In addition, the ventilation of this lung increased significantly (P less than 0.05). Mean end-tidal PCO2 of the lower lung increased from 4.1 to 4.2 kPa after opening the pleura, while that of the upper lung increased from 3.0 to 3.6 kPa (P less than 0.01). VD/VT decreased from 43 to 38% as the pleura was opened (P less than 0.01). During surgical handling of the lung, marked decreases in ventilation, compliance, carbon dioxide elimination and end-tidal PCO2 were observed in the upper lung. We conclude that ventilation-perfusion mismatch decreased on opening the pleura, and that neither opening the pleura nor the subsequent lung surgery (both lungs being ventilated) caused any clinically important derangements in haemodynamics or oxygenation.

Carbon dioxide elimination from each lung during endobronchial anaesthesia. Effects of posture and pulmonary arterial pressure.

The ventilation and carbon dioxide elimination of each lung, and pulmonary arterial pressure, were studied in 17 patients during the early phases of anaesthesia for pulmonary surgery. The patients were ventilated mechanically to moderate hypocapnia. Expired tidal volume and carbon dioxide elimination rate of the lung to be operated on, and of the other lung, were similar in the supine position. There was a significant (P less than 0.01) increase in ventilation and a decrease in end-tidal PCO2 of the upper lung after turning the patient on to the side. Simultaneously, the physiological deadspace fraction of tidal volume (VD/VT) increased from 42 to 45% (P less than 0.05). Mean pulmonary arterial pressure (MPAP) increased slightly as surgery on the chest wall commenced. A concomitant increase of carbon dioxide elimination from the upper lung occurred also, although the distribution of ventilation, between the lungs, was unchanged in comparison with the conditions during undisturbed anaesthesia. Individual changes in MPAP (delta MPAP) and corresponding changes in VD/VT (delta (VD/VT)) were negatively correlated (r = -0.68, P less than 0.01). The regression equation was delta (VD/VT) (%) = 0.7 - 0.83 X delta MPAP (mmHg). It was concluded that variations in pulmonary arterial pressure during surgical stimulation may significantly affect the pattern of carbon dioxide elimination in the lungs. However, there was no evidence that these effects were important clinically.